PMID- 9572719
TI  - Conditional associative learning and the hippocampal system.
AB  - Rats with lesions of the fornix, the dorsal hippocampus, or a control operation
      were trained on a spatial-visual conditional associative learning task in which
      they had to learn to associate particular locations with specific visual stimuli.
      Animals with damage of the fornix were able to learn the task at a rate
      comparable to that of the control animals, but the performance of the hippocampal
      rats was significantly impaired in comparison with that of both the control and
      the fornix groups. In a second experiment, lesions to the fornix or the dorsal
      hippocampus significantly impaired performance on a spatial working memory task,
      the eight-arm radial maze. These findings suggest that the interaction between
      the hippocampus and subcortical structures via the fornix may be critical only
      for certain types of spatial learning and memory.

PMID- 9572720
TI  - Hippocampal lesions enhance configural learning by reducing proactive
      interference.
AB  - Rats were trained on an operant conditional discrimination in which an ambiguous
      stimulus (X) indicated both the occasions on which responding in the presence of
      a second cue (A) would be reinforced and the occasions on which responding in the
      presence of a third cue (B) would not be reinforced (X --> A+, A-, X --> B-, B+).
      Both rats with neurotoxic lesions of the hippocampus and control rats learned
      this discrimination more rapidly when the training trials were widely spaced
      (mean intertrial interval of 8 min) than when they were massed (mean intertrial
      interval of 1 min). With spaced practice, lesioned and control rats learned this
      discrimination equally well. But when the training trials were massed, lesioned
      rats learned more rapidly than controls. At the end of training, performance of
      all rats was tested at three different intertrial intervals, 0.5 min, 1 min, and
      8 min. The control rats trained with 8-min intertrial intervals showed deficits
      in discrimination performance when the test intertrial interval was 0.5 min or 1
      min. An analysis of sequential effects indicated that a major source of this
      performance deficit was the control rats' failure to withhold responding on
      nonreinforced trials when those trials were immediately preceded by reinforced
      trials within 0.5 min or 1 min. In contrast, performance of lesioned rats was not
      affected by either the test intertrial interval or by the nature of preceding
      trials. Thus, with short intertrial intervals, hippocampal lesions may have
      improved learning or performance on a given trial by reducing proactive
      interference from the previous trial.

PMID- 9572721
TI  - Contingent versus incidental context processing during conditioning: dissociation
      after excitotoxic hippocampal plus dentate gyrus lesions.
AB  - This experiment explored whether excitotoxic hippocampus plus dentate gyrus
      (HPC/DG) lesions in rats would dissociate the differential processing of
      contextual cues during the performance of learned associations when (1) their
      processing during training is incidental to successful learning or (2) the
      solution of a discrimination problem is contingent on their processing. A series
      of training stages were conducted, beginning with appetitive conditioning to two
      stimuli (X and Y), each of which was trained in one of two different contexts
      (operant chambers A and B) (i.e., AX+, BY+). Conditioning was indexed as
      appetitive responding. The animals were then trained on a biconditional
      contextual discrimination with these same stimuli (AX+, AY-; BY+, BX-). The next
      stage involved conditioning trials to two new stimuli (W and Z), one in each
      context, while the animals were actively discriminating contexts A and B by
      continuing to perform the original biconditional discrimination (AX+, AY-, AW+;
      BY+, BX-, BZ+). Finally, they were trained on a second biconditional
      discrimination involving these new stimuli (AX+, AY-, AW+, AZ-; BY+, BX-, BZ+, BW
      ). The incidental use of context cues was examined by looking at the rate of
      conditioned responding to cues X, Y, W, and Z in their original training contexts
      or a different context; HPC/DG lesioned rats differed from controls in being
      unaffected by a change of context. The contingent use of context cues was
      examined by looking at performance of each of the two biconditional tasks; HPC/DG
      lesioned rats reached levels of conditional performance indistinguishable from
      those of controls. These findings point to two distinct ways in which contextual
      information is processed in the brain, revealing a dissociation between
      incidental and contingent processing of contextual cues after HPC/DG lesions.

PMID- 9572722
TI  - Priming of long-term potentiation induced by activation of metabotropic glutamate
      receptors coupled to phospholipase C.
AB  - Activation of metabotropic glutamate receptors (mGluRs) with 1-aminocyclopentane
      1S,3R-dicarboxylic acid 20 min prior to tetanus facilitates, or "primes,"
      subsequent induction of long-term potentiation (LTP; Cohen and Abraham, J
      Neurophysiol 1996;76:953-962). In the present study, we investigated the receptor
      specificity and associated second messenger pathways involved in the mGluR
      priming effect by using field potentials recorded from area CA1 of rat
      hippocampal slices. In controls, mild theta-burst or high-frequency (100 Hz)
      stimulation induced 16% and 21% LTP, respectively. A 10-min application of the
      group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) caused a transient
      depression of synaptic responses but a significant enhancement of subsequent LTP
      for both tetanus protocols (45% and 41% LTP, respectively). Maximal LTP, induced
      by stronger tetanization protocols, was not enhanced by DHPG, nor was mild LTP
      facilitated by post-tetanic application of DHPG. Priming with agonists selective
      for group II or III mGluRs had no effect on LTP. The mGluR antagonists L-2-amino
      3-phosphonopropionic acid and 1-aminoindan-1,5-dicarboxylic acid inhibited the
      LTP facilitatory effect of DHPG but not the transient response depression,
      whereas alpha-methyl-4-carboxyphenylglycine produced the opposite effects.
      Priming with N-methyl-D-aspartate or alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid did not facilitate LTP induction. Prior activation of
      muscarinic acetylcholine receptors produced at best a weak priming effect.
      Inhibition of phospholipase C by U-73122 completely abolished the priming of LTP
      by DHPG. We conclude that mGluR priming of LTP results from biochemical cascades
      triggered by activation of phospholipase C coupled to group I mGluRs.

PMID- 9572723
TI  - GABA(B) modulation improves sequence disambiguation in computational models of
      hippocampal region CA3.
AB  - Computational models of hippocampal region CA3 were used to study the role of
      theta rhythm in storage and retrieval of temporal sequences of neuronal activity
      patterns. Retrieval of multiple overlapping temporal sequences requires a
      mechanism for disambiguation, e.g., for choosing between two sequences with the
      same starting pattern but different final patterns (forked sequences). Modulatory
      input to the hippocampus from the medial septum may enhance the disambiguation of
      pattern sequences by causing phasic changes in the relative strength of afferent
      input and recurrent excitation. In the models, the strength of recurrent synaptic
      transmission is modulated by activation of GABA(B) receptors. Theta frequency
      inputs from the medial septum cause oscillations in the levels of GABA in the
      model, producing phasic changes in the strength of synaptic potentials during a
      theta cycle similar to those observed experimentally (Wyble et al., Soc Neurosci
      Abstr 1997;23: 197.7). These phasic changes in GABA(B) suppression improve
      sequence disambiguation in the simulations, as previously shown with analysis of
      a simpler model (Sohal and Hasselmo, Neural Comp 1998;10:889-902). In addition,
      tonic changes in levels of cholinergic modulation enhance the storage of forked
      sequences by preventing a strong influence of recurrent synapses during storage.

PMID- 9572724
TI  - Adolescent sexual behavior, drug use, and violence: increased reporting with
      computer survey technology.
AB  - Surveys of risk behaviors have been hobbled by their reliance on respondents to
      report accurately about engaging in behaviors that are highly sensitive and may
      be illegal. An audio computer-assisted self-interviewing (audio-CASI) technology
      for measuring those behaviors was tested with 1690 respondents in the 1995
      National Survey of Adolescent Males. The respondents were randomly assigned to
      answer questions using either audio-CASI or a more traditional self-administered
      questionnaire. Estimates of the prevalence of male-male sex, injection drug use,
      and sexual contact with intravenous drug users were higher by factors of 3 or
      more when audio-CASI was used. Increased reporting was also found for several
      other risk behaviors.

PMID- 9572725
TI  - A 100,000-year periodicity in the accretion rate of interplanetary dust 
AB  - Numerical modeling of the orbital evolution of interplanetary dust particles
      revealed that, over the past 1.2 million years, the rate of accretion of dust by
      Earth has varied by a factor of 2 to 3. These variations display a 100,000-year
      periodicity and are anticorrelated with Earth's changing orbital eccentricity.
      Extraterrestrial helium-3 concentrations in a deep-sea sediment core display a
      similar periodicity but are 50,000 years out of phase with the predicted
      variations. Also, because collisions between large bodies in the asteroid belt
      are inevitable, it is expected that large-amplitude stochastic variations on
      10(7)- to 10(8)-year time scales would be superimposed on the 10(5)-year periodic
      variations.

PMID- 9572726
TI  - Plutonium-fission xenon found in Earth's mantle 
AB  - Data from mid-ocean ridge basalt glasses indicate that the short-lived
      radionuclide plutonium-244 that was present during an early stage of the
      development of the solar system is responsible for roughly 30 percent of the
      fissiogenic xenon excesses in the interior of Earth today. The rest of the
      fissiogenic xenon can be ascribed to the spontaneous fission of still live
      uranium-238. This result, in combination with the refined determination of xenon
      129 excesses from extinct iodine-129, implies that the accretion of Earth was
      finished roughly 50 million to 70 million years after solar system formation and
      that the atmosphere was formed by mantle degassing.

PMID- 9572727
TI  - Reaction sequence of iron sulfide minerals in bacteria and their use as
      biomarkers.
AB  - Some bacteria form intracellular nanometer-scale crystals of greigite (Fe3S4)
      that cause the bacteria to be oriented in magnetic fields. Transmission electron
      microscope observations showed that ferrimagnetic greigite in these bacteria
      forms from nonmagnetic mackinawite (tetragonal FeS) and possibly from cubic FeS.
      These precursors apparently transform into greigite by rearrangement of iron
      atoms over a period of days to weeks. Neither pyrrhotite nor pyrite was found.
      These results have implications for the interpretation of the presence of
      pyrrhotite and greigite in the martian meteorite ALH84001.

PMID- 9572728
TI  - Clams As recorders of ocean ridge volcanism and hydrothermal vent field activity 
AB  - The clam Calyptogena magnifica lives at abyssal depths in association with
      hydrothermal venting on midocean ridges. Analysis of strontium/calcium ratios in
      C. magnifica shells provides a temperature proxy with submonthly time resolution.
      A 21-year strontium/calcium record of two clams from 9 degrees50'N on the East
      Pacific Rise captures the known 1991 and 1992 eruptive events, documents several
      additional events between 1992 and 1996, and demonstrates the absence of major
      hydrothermal episodes during the period 1974 to 1991. These clam archives can
      increase our understanding of the thermal and chemical history of midocean ridge
      hydrothermal and volcanic activity on decadal time scales.

PMID- 9572729
TI  - Pressure-induced amorphization and negative thermal expansion in ZrW2O8 
AB  - It has recently been shown that zirconium tungstate (ZrW2O8) exhibits isotropic
      negative thermal expansion over its entire temperature range of stability. This
      rather unusual behavior makes this compound particularly suitable for testing
      model predictions of a connection between negative thermal expansion and pressure
      induced amorphization. High-pressure x-ray diffraction and Raman scattering
      experiments showed that ZrW2O8 becomes progressively amorphous from 1.5 to 3.5
      gigapascals. The amorphous phase was retained after pressure release, but the
      original crystalline phase returned after annealing at 923 kelvin. The results
      indicate a general trend between negative thermal expansion and pressure-induced
      amorphization in highly flexible framework structures.

PMID- 9572730
TI  - Self-trapping of dark incoherent light beams 
AB  - "Dark beams" are nonuniform optical beams that contain either a one-dimensional
      (1D) dark stripe or a two-dimensional (2D) dark hole resulting from a phase
      singularity or an amplitude depression in their optical field. Thus far, self
      trapped dark beams (dark solitons) have been observed using coherent light only.
      Here, self-trapped dark incoherent light beams (self-trapped dark incoherent
      wavepackets) were observed. Both dark stripes and dark holes nested in a broad
      partially spatially incoherent wavefront were self-trapped to form dark solitons
      in a host photorefractive medium. These self-trapped 1D and 2D dark beams induced
      refractive-index changes akin to planar and circular dielectric waveguides. The
      experiments introduce the possibility of controlling high-power coherent laser
      beams with low-power incoherent light sources such as light emitting diodes.

PMID- 9572731
TI  - Ultrathin films of a polyelectrolyte with layered architecture 
AB  - Posttransfer modification of preformed Langmuir-Blodgett films of poly(tert-butyl
      methacrylate) and poly(tert-butyl acrylate) by gaseous hydrochloric acid yields
      films with layered architecture of poly(methacrylic acid) and poly(acrylic acid),
      respectively. X-ray reflectivity and infrared spectroscopy confirm monolayer by
      monolayer transfer of the source polymers and their transformation to acid
      multilayer assemblies with retention of low surface roughnesses. The
      incorporation of cross-linking groups into the system offers the possibility for
      further chemical modification to produce ultrathin films of model networks
      desirable for bioadsorption studies and as hydrophilic spacing layers for
      tethered membranes.

PMID- 9572732
TI  - The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes.
AB  - Xenopus oocytes convert a continuously variable stimulus, the concentration of
      the maturation-inducing hormone progesterone, into an all-or-none biological
      response-oocyte maturation. Here evidence is presented that the all-or-none
      character of the response is generated by the mitogen-activated protein kinase
      (MAPK) cascade. Analysis of individual oocytes showed that the response of MAPK
      to progesterone or Mos was equivalent to that of a cooperative enzyme with a Hill
      coefficient of at least 35, more than 10 times the Hill coefficient for the
      binding of oxygen to hemoglobin. The response can be accounted for by the
      intrinsic ultrasensitivity of the oocyte's MAPK cascade and a positive feedback
      loop in which the cascade is embedded. These findings provide a biochemical
      rationale for the all-or-none character of this cell fate switch.

PMID- 9572733
TI  - Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell
      shape change.
AB  - Integrin-mediated reorganization of cell shape leads to an altered cellular
      phenotype. Disruption of the actin cytoskeleton, initiated by binding of soluble
      antibody to alpha5beta1 integrin, led to increased expression of the collagenase
      1 gene in rabbit synovial fibroblasts. Activation of the guanosine triphosphate
      binding protein Rac1, which was downstream of the integrin, was necessary for
      this process, and expression of activated Rac1 was sufficient to increase
      expression of collagenase-1. Rac1 activation generated reactive oxygen species
      that were essential for nuclear factor kappa B-dependent transcriptional
      regulation of interleukin-1alpha, which, in an autocrine manner, induced
      collagenase-1 gene expression. Remodeling of the extracellular matrix and
      consequent alterations of integrin-mediated adhesion and cytoarchitecture are
      central to development, wound healing, inflammation, and malignant disease. The
      resulting activation of Rac1 may lead to altered gene regulation and alterations
      in cellular morphogenesis, migration, and invasion.

PMID- 9572734
TI  - Modular organization of cognitive systems masked by interhemispheric integration.
AB  - After resection of the corpus callosum, V.J., a left-handed woman with left
      hemisphere dominance for spoken language, demonstrated a dissociation between
      spoken and written language. In the key experiment, words flashed to V.J.'s
      dominant left hemisphere were easily spoken out loud, but could not be written.
      However, when the words were flashed to her right hemisphere, she could not speak
      them out loud, but could write them with her left hand. This marked dissociation
      supports the view that spoken and written language output can be controlled by
      independent hemispheres, even though before her hemispheric disconnection, they
      appeared as inseparable cognitive entities.

PMID- 9572735
TI  - Thymocyte development in the absence of pre-T cell receptor extracellular
      immunoglobulin domains.
AB  - Immature thymocytes express a pre-T cell receptor (pre-TCR) composed of the
      TCRbeta chain paired with pre-Talpha. Signals from this receptor are essential
      for passage of thymocytes through a key developmental checkpoint in the thymus.
      These signals were efficiently delivered in vivo by a truncated form of the
      murine pre-TCR that lacked all of its extracellular immunoglobulin domains. De
      novo expression of the truncated pre-TCR or an intact alphabetaTCR was sufficient
      to activate characteristic TCR signaling pathways in a T cell line. These
      findings support the view that recognition of an extracellular ligand is not
      required for pre-TCR function.

PMID- 9572736
TI  - Replication checkpoint enforced by kinases Cds1 and Chk1.
AB  - Cdc2, the kinase that induces mitosis, is regulated by checkpoints that couple
      mitosis to the completion of DNA replication and repair. The repair checkpoint
      kinase Chk1 regulates Cdc25, a phosphatase that activates Cdc2. Effectors of the
      replication checkpoint evoked by hydroxyurea (HU) are unknown. Treatment of
      fission yeast with HU stimulated the kinase Cds1, which appears to phosphorylate
      the kinase Wee1, an inhibitor of Cdc2. The protein kinase Cds1 was also required
      for a large HU-induced increase in the amount of Mik1, a second inhibitor of
      Cdc2. HU-induced arrest of cell division was abolished in cds1 chk1 cells. Thus,
      Cds1 and Chk1 appear to jointly enforce the replication checkpoint.

PMID- 9572737
TI  - Chaos, persistence, and evolution of strain structure in antigenically diverse
      infectious agents.
AB  - The effects of selection by host immune responses on transmission dynamics was
      analyzed in a broad class of antigenically diverse pathogens. Strong selection
      can cause pathogen populations to stably segregate into discrete strains with
      nonoverlapping antigenic repertoires. However, over a wide range of intermediate
      levels of selection, strain structure is unstable, varying in a manner that is
      either cyclical or chaotic. These results have implications for the
      interpretation of longitudinal epidemiological data on strain or serotype
      abundance, design of surveillance strategies, and the assessment of multivalent
      vaccine trials.

PMID- 9572738
TI  - Identification of non-heme diiron proteins that catalyze triple bond and epoxy
      group formation.
AB  - Acetylenic bonds are present in more than 600 naturally occurring compounds.
      Plant enzymes that catalyze the formation of the Delta12 acetylenic bond in 9
      octadecen-12-ynoic acid and the Delta12 epoxy group in 12,13-epoxy-9-octadecenoic
      acid were characterized, and two genes, similar in sequence, were cloned. When
      these complementary DNAs were expressed in Arabidopsis thaliana, the content of
      acetylenic or epoxidated fatty acids in the seeds increased from 0 to 25 or 15
      percent, respectively. Both enzymes have characteristics similar to the membrane
      proteins containing non-heme iron that have histidine-rich motifs.

PMID- 9572739
TI  - A role for the AKT1 potassium channel in plant nutrition.
AB  - In plants, potassium serves an essential role as an osmoticum and charge carrier.
      Its uptake by roots occurs by poorly defined mechanisms. To determine the role of
      potassium channels in planta, we performed a reverse genetic screen and
      identified an Arabidopsis thaliana mutant in which the AKT1 channel gene was
      disrupted. Roots of this mutant lacked inward-rectifying potassium channels and
      displayed reduced potassium (rubidium-86) uptake. Compared with wild type, mutant
      plants grew poorly on media with a potassium concentration of 100 micromolar or
      less. These results and membrane potential measurements suggest that the AKT1
      channel mediates potassium uptake from solutions that contain as little as 10
      micromolar potassium.

PMID- 9572740
TI  - Knowing where and getting there: a human navigation network.
AB  - The neural basis of navigation by humans was investigated with functional
      neuroimaging of brain activity during navigation in a familiar, yet complex
      virtual reality town. Activation of the right hippocampus was strongly associated
      with knowing accurately where places were located and navigating accurately
      between them. Getting to those places quickly was strongly associated with
      activation of the right caudate nucleus. These two right-side brain structures
      function in the context of associated activity in right inferior parietal and
      bilateral medial parietal regions that support egocentric movement through the
      virtual town, and activity in other left-side regions (hippocampus, frontal
      cortex) probably involved in nonspatial aspects of navigation. These findings
      outline a network of brain areas that support navigation in humans and link the
      functions of these regions to physiological observations in other mammals.

PMID- 9572741
TI  - Britain's new strategy for tackling drugs misuse. Shows a welcome emphasis on
      evidence.

PMID- 9572742
TI  - Preventing recurrent coronary heart disease. We need to attend more to
      implementing evidence based practice.

PMID- 9572743
TI  - Economic globalisation and its effect on health. Some diseases could be
      eradicated for the cost of a couple of fighter planes.

PMID- 9572744
TI  - Does the WHO have a role in Europe?. There is more to "Europe" than you might
      think.

PMID- 9572745
TI  - Allocating the WHO's resources rationally. One cheer for the who's proposed
      changes in regional budgets?

PMID- 9572746
TI  - Knowing when to say "no" on the student elective. Students going on electives
      abroad need clinical guidelines.

PMID- 9572747
TI  - Male subfertility: is pregnancy the only issue?. Psychological responses matter
      too-and are different in men.

PMID- 9572748
TI  - Letters to the editor: the new order. Please respond to articles using website,
      email, or disk-but not paper 

PMID- 9572749
TI  - Incidence of seroconversion to positivity for hepatitis C antibody in repeat
      blood donors in England, 1993-5.
AB  - OBJECTIVE: To estimate the rate of seroconversion to positivity for hepatitis C
      antibody in repeat blood donors in England and to describe the probable routes of
      infection in these donors. DESIGN: Retrospective survey of blood donors becoming
      positive for hepatitis C antibody and of the results of donation testing.
      SETTING: The 14 blood centres in England. SUBJECTS: All repeat donors giving
      blood between January 1993 and December 1995. MAIN OUTCOME MEASURES: Number of
      donors developing hepatitis C between donations during the three years of testing
      for hepatitis C antibody at English blood centres and the rate of seroconversion
      among repeat blood donors. Probable routes of infection. RESULTS: 14 donors
      during 1993-5 fulfilled the case definition for seroconversion to positivity for
      hepatitis C antibody. The estimated seroconversion rate for infection with
      hepatitis C in repeat donors was 0.26 per 100 000 person years (95% confidence
      interval 0.15 to 0.43). Counselling after diagnosis found that four of these
      donors had risk factors specified in the criteria excluding people from giving
      blood but these factors had not come to light before donation. Another of the
      donors who seroconverted had a risk factor that has since been included in the
      exclusion criteria. Heterosexual intercourse was considered to be the most likely
      route of infection for five of the 14 donors. CONCLUSIONS: The rate of
      seroconversion for positivity to hepatitis C antibody in repeat blood donors in
      England was extremely low. During 1993-5 fewer than 1 in 450 000 donations were
      estimated to have come from repeat donors who had become positive for hepatitis C
      antibody since the previous donation.

PMID- 9572750
TI  - Screening for human T cell leukaemia/lymphoma virus among blood donors in Sweden:
      cost effectiveness analysis.
AB  - OBJECTIVE: To analyse the cost effectiveness of a national programme to screen
      blood donors for infection with the human T cell leukaemia/lymphoma virus.
      DESIGN: Three models for calculating the costs and benefits of screening were
      developed. The first model analysed the cost of continuously testing all
      donations; the second analysed the cost of initially testing new blood donors and
      then retesting them after five years; the third analysed the cost of testing
      donors only at the time of their first donation. Patients who had received blood
      components from donors confirmed to be infected with the virus were offered
      testing. SETTING: Sweden. MAIN OUTCOME MEASURES: Prevalence of infection with the
      virus among blood donors, the risk of transmission of the virus, screening costs,
      and the outcome of infection. RESULTS: 648 497 donations were tested for the
      virus; 1625 samples tested positive by enzyme linked immunosorbent assay. 6 were
      confirmed positive by western blotting. The prevalence of infection with the
      virus was 2/100 000 donors. 35 patients who had received blood infected with the
      virus were tested; 3 were positive. The cost of testing every donation was
      calculated to be $3.02m (1.88m pounds); this is 18 times higher than the cost of
      testing new donors only, and only 1 additional positive donor would be discovered
      in 7 years. Regardless of the model used, screening was estimated to prevent only
      1 death every 200 years at a minimum cost of $36m (22.5m pounds). CONCLUSION:
      Based on these estimates the Swedish National Board of Health and Welfare decided
      that only new blood donors would be screened for infection with the virus.

PMID- 9572751
TI  - Drug resistant tuberculosis in prisons in Azerbaijan: case study.
AB  - OBJECTIVES: To document the existence of drug resistance in a tuberculosis
      treatment programme that adheres strictly to the DOTS principles (directly
      observed treatment, short course) and to determine the extent of drug resistance
      in a prison setting in one of the republics of the former Soviet Union. DESIGN:
      Case study. SETTING: Central Penitentiary Hospital in Baku, the referral centre
      for tuberculosis patients from all prisons in Azerbaijan. SUBJECTS: Prisoners
      with tuberculosis: 28 selected patients not responding clinically or
      bacteriologically to the standard treatment (group 1) and 38 consecutive patients
      at admission to the programme (group 2). MAIN OUTCOME MEASURES: Drug resistance
      of Mycobacterium tuberculosis strains grown from sputum. RESULTS: All the non
      responding patients (group 1) had strains resistant to at least one drug. 25
      (89%) of the non-responding patients and nine (24%) of the consecutive patients
      had M tuberculosis strains resistant to both rifampicin and isoniazid. A further
      17 patients in group 2 had strains resistant to one or more first line drugs.
      CONCLUSIONS: Drug resistant M tuberculosis strains are common in prisons in
      Azerbaijan. Tuberculosis problems tend to be worse in prisons, but prisoners and
      former prisoners may have an important role in the transmission of tuberculosis,
      particularly of drug resistant forms, in the community. National programmes to
      control tuberculosis will have to take into account and address the problems in
      prisons to ensure their success.

PMID- 9572752
TI  - Prospective, hospital based study of fever in children in the United Kingdom who
      had recently spent time in the tropics.

PMID- 9572753
TI  - Determinants of car travel on daily journeys to school: cross sectional survey of
      primary school children.

PMID- 9572755
TI  - British practitioners in italy 

PMID- 9572754
TI  - Evaluation of indices of obesity in men: descriptive study.

PMID- 9572756
TI  - The new NHS: national health service. Mr. Bevan's statement 

PMID- 9572758
TI  - Secondary prevention clinics for coronary heart disease: randomised trial of
      effect on health.
AB  - OBJECTIVE: To evaluate the effects of secondary prevention clinics run by nurses
      in general practice on the health of patients with coronary heart disease.
      DESIGN: Randomised controlled trial of clinics over one year with assessment by
      self completed postal questionnaires and audit of medical records at the start
      and end of the trial. SETTING: Random sample of 19 general practices in northeast
      Scotland. SUBJECTS: 1173 patients (685 men and 488 women) under 80 years with
      working diagnoses of coronary heart disease who did not have terminal illness or
      dementia and were not housebound. INTERVENTION: Clinic staff promoted medical and
      lifestyle aspects of secondary prevention and offered regular follow up. MAIN
      OUTCOME MEASURES: Health status measured by the SF-36 questionnaire, chest pain
      by the angina type specification, and anxiety and depression by the hospital
      anxiety and depression scale. Use of health services before and during the study.
      RESULTS: There were significant improvements in six of eight health status
      domains (all functioning scales, pain, and general health) among patients
      attending the clinic. Role limitations attributed to physical problems improved
      most (adjusted difference 8.52, 95% confidence interval 4.16 to 12. 9). Fewer
      patients reported worsening chest pain (odds ratio 0.59, 95% confidence interval
      0.37 to 0.94). There were no significant effects on anxiety or depression. Fewer
      intervention group patients required hospital admissions (0.64, 0.48 to 0.86),
      but general practitioner consultation rates did not alter. CONCLUSIONS: Within
      their first year secondary prevention clinics improved patients' health and
      reduced hospital admissions.

PMID- 9572757
TI  - Secondary prevention in coronary heart disease: baseline survey of provision in
      general practice.
AB  - OBJECTIVE: To determine secondary preventive treatment and habits among patients
      with coronary heart disease in general practice. DESIGN: Process of care data on
      a random sample of patients were collected from medical records. Health and
      lifestyle data were collected by postal questionnaire (response rate 71%).
      SETTING: Stratified, random sample of general practices in Grampian. SUBJECTS:
      1921 patients aged under 80 years with coronary heart disease identified from pre
      existing registers of coronary heart disease and nitrate prescriptions. MAIN
      OUTCOME MEASURES: Treatment with aspirin, beta blockers, and angiotensin
      converting enzyme inhibitors. Management of lipid concentrations and hypertension
      according to local guidelines. Dietary habits (dietary instrument for nutritional
      evaluation score), physical activity (health practice indices), smoking, and body
      mass index. RESULTS: 825/1319 (63%) patients took aspirin. Of 414 patients with
      recent myocardial infarction, 131 (32%) took beta blockers, and of 257 with heart
      failure, 102 (40%) took angiotensin converting enzyme inhibitors. Blood pressure
      was managed according to current guidelines for 1566 (82%) patients but lipid
      concentrations for only 133 (17%). 673 of 1327 patients (51%) took little or no
      exercise, 245 of 1333 (18%) were current smokers, 808 of 1264 (64%) were
      overweight, and 627 of 1213 (52%) ate more fat than recommended. CONCLUSION: In
      terms of secondary prevention, half of patients had at least two aspects of their
      medical management that were suboptimal and nearly two thirds had at least two
      aspects of their health behaviour that would benefit from change. There seems to
      be considerable potential to increase secondary prevention of coronary heart
      disease in general practice.

PMID- 9572759
TI  - Investigating and managing infertility in general practice.

PMID- 9572760
TI  - Anaphylaxis.

PMID- 9572761
TI  - Sudan: in through the back door.

PMID- 9572762
TI  - Needs assessment: from theory to practice.

PMID- 9572763
TI  - Loss in late life.

PMID- 9572764
TI  - The intracluster correlation coefficient in cluster randomisation.

PMID- 9572765
TI  - How the cycle of poverty and ill health can be broken.

PMID- 9572766
TI  - Doctors can do something about poverty.

PMID- 9572767
TI  - Developed countries could pay for hepatitis B vaccination in developing
      countries.

PMID- 9572768
TI  - Africa needs leadership by Africans of high calibre.

PMID- 9572769
TI  - Improved bacteriological data are needed to give uniform reporting of
      tuberculosis in Europe.

PMID- 9572770
TI  - An ethical code for everybody in health care. The role and limitations of such a
      code need to be recognised.

PMID- 9572771
TI  - Accidental child poisoning. Child resistant packaging should be used on all over
      the counter drugs.

PMID- 9572772
TI  - Report on cleft lip and palate surgery. Uk results could soon surpass those
      elsewhere.

PMID- 9572773
TI  - Evaluating health promotion is complex.

PMID- 9572775
TI  - Maurice anthony barker 

PMID- 9572774
TI  - Older women should receive annual breast examinations.

PMID- 9572776
TI  - BMA calls for risk management approach to stress 

PMID- 9572777
TI  - Valedictory lecture 

PMID- 9572778
TI  - Plunged in at the deep end 

PMID- 9572779
TI  - Home glucose monitoring, who started it? 

PMID- 9572781
TI  - European health care reform: analysis of current strategies 

PMID- 9572780
TI  - Violence against women 

PMID- 9572782
TI  - When and how to assess fast-changing technologies: A comparative study of medical
      applications of four generic technologies 

PMID- 9572783
TI  - New cases of hepatitis C are rare in repeat blood donors 

PMID- 9572784
TI  - Screening blood for human T cell leukaemia/lymphoma virus is not cost effective
      in sweden 

PMID- 9572785
TI  - Multidrug resistant tuberculosis is common in azerbaijani prisons 

PMID- 9572787
TI  - Increased secondary prevention of coronary heart disease benefits general
      practice patients 

PMID- 9572786
TI  - Distance to school and car ownership are greatest determinants of car travel to
      school 

PMID- 9572788
TI  - Invited editorial on "Effects of chest wall vibration on breathlessness during
      hypercapnic ventilatory response".

PMID- 9572789
TI  - Effects of chest wall vibration on breathlessness during hypercapnic ventilatory
      response.
AB  - Vibratory stimulation applied to the chest wall during inspiration reduces the
      intensity of breathlessness, whereas the same stimulation during expiration has
      no effect or may increase breathlessness. The purpose of the present study was to
      determine whether vibration reduced the intensity of breathlessness during
      progressive hypercapnia with and without the addition of an external resistive
      load. A second objective was to see whether the mouth occlusion pressure at 0.2 s
      (P0.2) was reduced by the vibratory stimulation. Hypercapnic ventilatory response
      was conducted in 10 healthy male volunteers with simultaneous measurement of
      visual analog scale, P0.2, and minute ventilation. Hypercapnic ventilatory
      response was performed and randomly combined with or without vibratory
      stimulation (100 Hz) as well as with or without inspiratory load. With
      inspiratory load, in-phase vibration did not cause any significant changes in the
      slopes of P0.2 and minute ventilation to CO2, whereas the slope of visual analog
      scale to CO2 significantly decreased from 0.47 +/- 0.15 to 0.34 +/- 0.11 (SE)
      cm/Torr (P < 0.05). We conclude that in-phase vibration could decrease the slope
      of breathlessness elicited by inspiratory load combined with hypercapnia without
      changing motor output.

PMID- 9572790
TI  - Anabolic steroids in part reverse glucocorticoid-induced alterations in rat
      diaphragm.
AB  - Animal and clinical studies have shown respiratory muscle dysfunction caused by
      treatment with glucocorticoids. The present study was designed to investigate
      whether anabolic steroids are able to antagonize the loss of diaphragm force
      induced by long-term low-dose methylprednisolone (MP) administration. Male adult
      rats were randomized to receive saline or MP (0.2 mg . kg-1 .day-1 sc) during 9
      mo, with or without nandrolone decanoate (ND; 1 mg . kg-1 . wm -1 im) during the
      last 3 mo. The approximately 10% reduction in force generation of isolated
      diaphragm bundles induced by MP was completely abolished by addition of ND. The
      MP-induced decrease in number of fibers expressing type IIb myosin heavy chains
      was not reversed by ND. MP slightly reduced type I, IIa, and IIx fiber cross
      sectional areas (CSA), but not type IIb fiber CSA. Addition of ND abolished the
      reduction in IIa and IIx fiber CSA. The MP-induced alterations in glycogenolytic
      activity and fatty acid oxidation capacity were not reversed by ND. In
      conclusion, the marked reduction in diaphragm force caused by long-term low-dose
      MP was completely abolished by addition of ND. ND in part also antagonized the
      effects of MP on diaphragm morphology but showed no beneficial effects on
      biochemical changes.

PMID- 9572791
TI  - Rapid reversibility of the allergen-induced pulmonary late-phase reaction by an
      intravenous beta2-agonist.
AB  - This study was performed to determine the degree to which beta2-adrenergic
      receptor agonists can reverse the allergen-induced late reduction in lung
      function. On two occasions, seven asthmatic subjects were administered
      terbutaline or its vehicle by intravenous infusion 7 h after inhaled allergen, at
      which point the forced expiratory volume in 1 s was 57% of baseline. On another
      occasion, terbutaline was infused at baseline to determine maximal attainable
      bronchodilation. After allergen challenge, terbutaline rapidly improved lung
      function. At the end of terbutaline infusion, the forced expiratory volume in 1 s
      reached 100 +/- 1.3% of baseline and 84.2 +/- 4.3% of maximal attainable value,
      but the bronchodilating effect of the beta-agonist did not plateau. The values
      for forced vital capacity were 102 +/- 1.3% of baseline and 95.1 +/- 3% of
      maximal attainable value. The kinetics of the terbutaline effect, when it was
      infused at baseline, were similar to those in the late phase. Because the late
      phase reduction in lung function is rapidly reversible by beta2-adrenergic
      agonists, we conclude that it is caused mainly by bronchial smooth muscle spasm.

PMID- 9572792
TI  - HRT preserves increases in bone mineral density and reductions in body fat after
      a supervised exercise program.
AB  - The aims of this study were to confirm our previous finding that hormone
      replacement therapy (HRT) augments exercise-induced increases in bone mineral
      density (BMD) in older women and to determine whether HRT preserves the
      adaptations when exercise is reduced or discontinued. The study included an 11-mo
      treatment phase and a 6-mo follow-up phase. Participants, aged 66 +/- 3 yr, were
      assigned to control (Con; n = 10), exercise (Ex; n = 18), HRT (n = 10), and
      Ex+HRT (n = 16) groups. HRT was continued during the follow-up. After the
      treatment phase, changes in total body BMD were -0.5 +/- 1.7, 1.5 +/- 1.4, 1.2 +/
      0.8, and 2.7 +/- 1.2% in Con, Ex, HRT, and Ex+HRT, respectively. Ex+HRT was more
      effective than HRT in increasing BMD of the total body and tended (P = 0.08) to
      be more effective at the lumbar spine. Ex+HRT was more effective than Ex in
      increasing BMD of the total body, lumbar spine, and trochanter. Exercise-induced
      gains in BMD were preserved during the follow-up only in those individuals on
      HRT. HRT also attenuated fat accumulation, particularly in the abdominal region,
      after the exercise program. These findings suggest that HRT is an important
      adjunct to exercise for the prevention not only of osteoporosis but also of
      diseases related to abdominal obesity.

PMID- 9572793
TI  - Head-up suspension in humans: effects on sympathetic vasomotor activity and
      cardiovascular responses.
AB  - We hypothesized that muscle sympathetic nerve activity (MSNA) and cardiovascular
      responses to the conventional head-up tilt (HUT) are different from those to head
      up suspension (HUS) because of antigravity muscle activity. The MSNA from the
      tibial nerve, heart rate, blood pressure, stroke volume, cardiac output, and calf
      blood flow were measured in 13 healthy young subjects. Left atrial diameter was
      measured by two-dimensional echocardiography in another nine subjects. The
      resting MSNA and cardiovascular responses at a low level (20 degrees) of
      orthostasis were similar during both modes. At higher levels (40 and 60 degrees),
      the responses of MSNA, heart rate, stroke volume, and cardiac output were
      significantly stronger and there was a smaller reduction in calf blood flow
      during HUT than during HUS (P < 0.05). Left atrial diameter was decreased
      significantly from the resting values during HUT and HUS without any significant
      difference between the modes of orthostasis. The results provide evidence that
      the engagement of antigravity muscles during HUT may have additive effects on
      sympathetic vasoconstrictor and cardiovascular responses to orthostatic stress.

PMID- 9572794
TI  - Effect of the TI/TE ratio on mean intratracheal pressure in high-frequency
      oscillatory ventilation.
AB  - In high-frequency oscillatory ventilation (HFOV), an adequate mean airway
      pressure is crucial for successful ventilation and optimal gas exchange, but air
      trapping cannot be detected by the usual measurement at the y piece.
      Intratracheal pressures produced by the high-frequency oscillators HFV-Infantstar
      (IS), Babylog 8000 (BL), and the SensorMedics 3100A (SM) [the latter with either
      30% (SM30) or 50% (SM50) inspiratory time] were investigated in four anesthetized
      tracheotomized female piglets that were 1 day old and weighed 1.6-1.9 kg (mean
      1.76 kg). The endotracheal tube was repeatedly clamped while the piglets were
      ventilated with an oscillation frequency of 10 Hz, and the airway pressure distal
      of the clamp was recorded as a measure of average intrapulmonary pressure during
      oscillation. Clamping resulted in a significant decrease of mean airway pressure
      when the piglets were ventilated with SM30 (-0.86 cmH2O), BL (-0.66 cmH2O), and
      IS (-0.71 cmH2O), but airway pressure increased by a mean of 0.76 cmH2O with
      SM50. Intratracheal pressure, when measured by a catheter pressure transducer at
      various oscillation frequencies, was lower than at the y piece by 0.4-0.9 cmH2O
      (SM30), 0.3-3 cmH2O (BL), and 1-4.7 cmH2O (IS) but was 0.4-0.7 cmH2O higher with
      SM50. We conclude that the inspiratory-to-expiratory time (TI/TE) ratio
      influences the intratracheal and intrapulmonary pressures in HFOV and may sustain
      a mean pressure gradient between the y piece and the trachea. A TI/TE ratio < 1:1
      may be useful to avoid air trapping when HFOV is used.

PMID- 9572795
TI  - Acetylcholine and substance P stimulate bronchial epithelial cells to release
      eosinophil chemotactic activity.
AB  - We investigated a role of neuroregulation in the release of eosinophil
      chemotactic activity (ECA) from bovine bronchial epithelial cells (BBEC). BBEC
      were stimulated with acetylcholine (ACh) and substance P (SP), and the
      supernatant fluids were tested for ECA by a blind-well chemotactic chamber
      technique. BBEC released ECA in response to ACh and SP in a dose- and time
      dependent manner. Checkerboard analysis showed that ECA in regard to ACh and SP
      was chemotactic rather than chemokinetic. Partial characterization revealed that
      ECA involved both lipids and peptides. The release of ECA in response to ACh and
      SP was inhibited by nonspecific and 5-specific lipoxygenase inhibitors and by
      cycloheximide (P < 0.01). Molecular-sieve column chromatography revealed that
      these mediators induced three molecular mass peaks (near 25 kDa, 9 kDa, and 400
      Da, respectively). The lowest peak, which represented the predominant activity,
      was blocked by leukotriene B4-receptor antagonist (P < 0. 01) but not by platelet
      activating factor-receptor antagonist. The release of leukotriene B4 in the
      supernatant fluids was increased in response to ACh and SP stimulation (P <
      0.01). Platelet-activating factor was not detected. These results raise the
      possibility of a role of neuroregulation for the elaboration of ECA in the
      airway.

PMID- 9572796
TI  - Developmental change in isoproterenol-mediated relaxation of pulmonary veins of
      fetal and newborn lambs.
AB  - beta-Adrenergic agonists are important regulators of perinatal pulmonary
      circulation. They cause vasodilation primarily via the adenyl cyclase-adenosine
      3',5'-cyclic monophosphate (cAMP) pathway. We examined the responses of isolated
      fourth-generation pulmonary veins of term fetal (145 +/- 2 days gestation) and
      newborn (10 +/- 1 days) lambs to isoproterenol, a beta-adrenergic agonist. In
      vessels preconstricted with U-46619 (a thromboxane A2 analog), isoproterenol
      induced greater relaxation in pulmonary veins of newborn lambs than in those of
      fetal lambs. The relaxation was eliminated by propranolol, a beta-adrenergic
      antagonist. Forskolin, an activator of adenyl cyclase, also caused greater
      relaxation of veins of newborn than those of fetal lambs. 8-Bromoadenosine 3',5'
      cyclic monophosphate, a cell membrane-permeable analog of cAMP, induced a similar
      relaxation of all vessels. Biochemical studies show that isoproterenol and
      forskolin induced a greater increase in cAMP content and in adenyl cyclase
      activity of pulmonary veins in the newborn than in the fetal lamb. These results
      demonstrate that beta-adrenergic-agonist-mediated relaxation of pulmonary veins
      increases with maturation. An increase in the activity of adenyl cyclase may
      contribute to the change.

PMID- 9572797
TI  - Pulmonary blood flow distribution during partial liquid ventilation.
AB  - Regional pulmonary blood flow was investigated with radiolabeled microspheres in
      four supine lambs during the transition from conventional mechanical ventilation
      (CMV) to partial liquid ventilation (PLV) and with incremental dosing of
      perfluorocarbon liquid to a cumulative dose of 30 ml/kg. Four lambs supported
      with CMV served as controls. Formalin-fixed, air-dried lungs were sectioned
      according to a grid; activity was quantitated with a multichannel scintillation
      counter, corrected for weight, and normalized to mean flow. During CMV, flow in
      apical and hilar regions favored dependent lung (P < 0.001), with no gradient
      across transverse planes from apex to diaphragm. During PLV the gradient within
      transverse planes found during CMV reversed, most notably in the hilar region,
      favoring nondependent lung (P = 0.03). Also during PLV, flow was profoundly
      reduced near the diaphragm (P < 0.001), and across transverse planes from apex to
      diaphragm a dose-augmented flow gradient developed favoring apical lung (P <
      0.01). We conclude that regional flow patterns during PLV partially reverse those
      noted during CMV and vary dramatically within the lung from apex to diaphragm.

PMID- 9572798
TI  - Altered mechanisms of sympathetic activation during rhythmic forearm exercise in
      heart failure.
AB  - In congestive heart failure (CHF), the mechanisms of exercise-induced
      sympathoexcitation are poorly defined. We compared the responses of sympathetic
      nerve activity directed to muscle (MSNA) and to skin (SSNA, peroneal
      microneurography) during rhythmic handgrip (RHG) at 25% of maximal voluntary
      contraction and during posthandgrip circulatory arrest (PHG-CA) in CHF patients
      with those of an age-matched control group. During RHG, the CHF patients fatigued
      prematurely. At end exercise, the increase in MSNA was similar in both groups
      (CHF patients, n = 12; controls, n = 10). However, during PHG-CA, in the controls
      MSNA returned to baseline, whereas it remained elevated in CHF patients (P <
      0.05). Similarly, at end exercise, the increase in SSNA was comparable in both
      groups (CHF patients, n = 11; controls, n = 12), whereas SSNA remained elevated
      during PHG-CA in CHF patients but not in the controls (P < 0.05). In a separate
      control group (n = 6), even high-intensity static handgrip was not accompanied by
      sustained elevation of SSNA during PHG-CA. 31P-nuclear magnetic resonance
      spectroscopy during RHG demonstrated significant muscle acidosis and accumulation
      of inorganic phosphate in CHF patients (n = 7) but not in controls (n = 9). We
      conclude that in CHF patients rhythmic forearm exercise leads to premature
      fatigue and accumulation of muscle metabolites. The prominent PHG-CA response of
      MSNA and SSNA in CHF patients suggests activation of the muscle metaboreflex.
      Because, in contrast to controls, in CHF patients both MSNA and SSNA appear to be
      under muscle metaboreflex control, the mechanisms and distribution of sympathetic
      outflow during exercise appear to be different from normal.

PMID- 9572799
TI  - Coordination between glottic adductor muscle and diaphragm EMG activity in fetal
      lambs in utero.
AB  - It has previously been reported that active glottic adduction is present during
      prolonged apneas but absent during periods of breathing movements in fetal lambs
      in utero. The present study was aimed at examining the precise coordination
      between fetal breathing movements [diaphragm electromyographic (EMG) activity (Di
      EMG)] and glottic adduction [thyroarytenoid muscle EMG activity (TA EMG)].
      Electrodes for electroencephalogram, eye movements, TA EMG, and Di EMG and an
      arterial catheter were surgically implanted in fetal lambs 123-142 days
      postconception. Polygraphic recordings were performed without sedation while the
      ewe breathed room air (n = 11) or various gas mixtures (hypoxia, n = 5;
      hyperoxia, n = 4; hypercapnia, n = 5; hypercapnia+hyperoxia, n = 5). Tonic TA EMG
      was observed throughout >90% of apneas (>6 s) in both non-rapid-eye-movement and
      rapid-eye-movement sleep, and when Di EMG frequency decreased in rapid-eye
      movement sleep. In all but two fetuses, TA EMG was immediately inhibited when Di
      EMG appeared. Altering blood gases did not modify these results. In conclusion,
      Di EMG and TA EMG are well coordinated in late gestation in fetal lambs, except
      in a few cases. These findings may have consequences for understanding the
      pathogenesis of mixed/obstructive apneas of prematurity.

PMID- 9572800
TI  - Partial liquid ventilation improves gas exchange and increases EELV in acute lung
      injury.
AB  - Gas exchange is improved during partial liquid ventilation with perfluorocarbon
      in animal models of acute lung injury. The specific mechanisms are unproved. We
      measured end-expiratory lung volume (EELV) by null-point body plethysmography in
      anesthetized sheep. Measurements of gas exchange and EELV were made before and
      after acute lung injury was induced with intravenous oleic acid to decrease EELV
      and worsen gas exchange. Measurements of gas exchange and EELV were again
      performed after partial liquid ventilation with 30 ml/kg of perfluorocarbon and
      compared with gas-ventilated controls. Oxygenation was significantly improved
      during partial liquid ventilation, and EELV (composite of gas and liquid) was
      significantly increased, compared with preliquid ventilation values and gas
      ventilated controls. We conclude that partial liquid ventilation may directly
      recruit consolidated alveoli in the lung-injured sheep and that this may be one
      mechanism whereby gas exchange is improved.

PMID- 9572801
TI  - Metabolic and hemodynamic responses of lower limb during exercise in patients
      with COPD.
AB  - Premature lactic acidosis during exercise in patients with chronic obstructive
      pulmonary disease (COPD) may play a role in exercise intolerance. In this study,
      we evaluated whether the early exercise-induced lactic acidosis in these
      individuals can be explained by changes in peripheral O2 delivery (O2).
      Measurements of leg blood flow by thermodilution and of arterial and femoral
      venous blood gases, pH, and lactate were obtained during a standard incremental
      exercise test to capacity in eight patients with severe COPD and in eight age
      matched controls. No significant difference was found between the two groups in
      leg blood flow at rest or during exercise at the same power outputs. Blood
      lactate concentrations and lactate release from the lower limb were greater in
      COPD patients at all submaximal exercise levels (all P < 0.05). Leg D02 at a
      given power output was not significantly different between the two groups, and no
      significant correlation was found between this parameter and blood lactate
      concentrations. COPD patients had lower arterial and venous pH at submaximal
      exercise, and there was a significant positive correlation between venous pH at
      40 W and the peak O2 uptake (r = 0.91, P < 0.0001). The correlation between
      venous pH and peak O2 uptake suggests that early muscle acidosis may be involved
      in early exercise termination in COPD patients. The early lactate release from
      the lower limb during exercise could not be accounted for by changes in
      peripheral O2. The present results point to skeletal muscle dysfunction as being
      responsible for the early onset of lactic acidosis in COPD.

PMID- 9572802
TI  - Effect of hypohydration on gastric emptying and intestinal absorption during
      exercise.
AB  - Dehydration and hyperthermia may impair gastric emptying (GE) during exercise;
      the effect of these alterations on intestinal water flux (WF) is unknown. Thus
      the purpose of this study was to determine the effect of hypohydration (
      approximately 2.7% body weight) on GE and WF of a water placebo (WP) during
      cycling exercise (85 min, 65% maximal oxygen uptake) in a cool environment (22
      degrees C) and to also compare GE and WF of three carbohydrate-electrolyte
      solutions (CES) while the subjects were hypohydrated. GE and WF were determined
      simultaneously by a nasogastric tube placed in the gastric antrum and via a
      multilumen tube that spanned the duodenum and the first 25 cm of jejunum.
      Hypohydration was attained 12-16 h before experiments by low-intensity exercise
      in a hot (45 degrees C), humid (relative humidity 50%) environment. Seven healthy
      subjects (age 26.7 +/- 1.7 yr, maximal oxygen uptake 55.9 +/- 8.2 ml . kg-1 . min
      1) ingested either WP or a 6% (330 mosmol), 8% (400 mosmol), or a 9% (590 mosmol)
      CES the morning following hypohydration. For comparison, subjects ingested WP
      after a euhydration protocol. Solutions ( approximately 2.0 liters total) were
      ingested as a large bolus (4.6 ml/kg body wt) 5 min before exercise and as small
      serial feedings (2.3 ml/kg body wt) every 10 min of exercise. Average GE rates
      were not different among conditions (P > 0.05). Mean (+/-SE) values for WF were
      also similar (P > 0.05) for the euhydration (15.3 +/- 1.7 ml . cm-1 . h-1) and
      hypohydration (18.3 +/- 2.6 ml . cm-1 . h-1) experiments. During exercise after
      hypohydration, water absorption was greater (P < 0.05) with ingestion of WP (18.3
      +/- 2. 6) and the 6% CES (16.5 +/- 3.7), compared with the 8% CES (6.9 +/- 1.5)
      and the 9% CES (1.8 +/- 1.7). Mean values for final core temperature (38.6 +/-
      0.1 degrees C), heart rate (152 +/- 1 beats/min), and change in plasma volume (
      5.7 +/- 0.7%) were similar among experimental trials. We conclude that 1)
      hypohydration to approximately 3% body weight does not impair GE or fluid
      absorption during moderate exercise when ingesting WP, and 2) hyperosmolality
      (>400 mosmol) reduced WF in the proximal intestine.

PMID- 9572803
TI  - Nicotine impairs histamine-induced increases in macromolecular efflux: role of
      oxygen radicals.
AB  - Nicotine, a major component of cigarettes and smokeless tobacco, has toxic
      effects on endothelium and impairs reactivity of resistance arterioles in
      response to agonists that stimulate the synthesis and/or release of nitric oxide.
      However, the effect of nicotine on nitric oxide synthase-dependent increases in
      macromolecular transport is not known. Thus our first goal was to determine the
      effect of nicotine on histamine-induced increases in macromolecular efflux. We
      used intravital microscopy and FITC dextran (mol wt 70, 000) (FITC-dextran-70K)
      to examine macromolecular extravasation from postcapillary venules in response to
      histamine before and after intravenous infusion of vehicle or nicotine.
      Extravasation of macromolecules was quantitated by counting venular leaky sites
      and calculating clearance (ml/s x 10(-6)) of FITC-dextran-70K. Histamine elicited
      reproducible increases in venular leaky sites and clearance in hamsters infused
      with vehicle. In contrast, nicotine infusion inhibited histamine-induced
      increases in macromolecular efflux. Histamine (1.0 and 5.0 micro M) elicited 19
      +/- 2 and 34 +/- 4 vs. 3 +/- 1 and 11 +/- 5 leaky sites per 0.11 cm2, before vs.
      after nicotine infusion, respectively (P < 0.05). Histamine-induced clearance of
      FITC-dextran-70K was also impaired after infusion of nicotine. Our second goal
      was to examine whether alterations in histamine-induced increases in
      macromolecular efflux by nicotine may be related to the production of oxygen
      radicals. Application of superoxide dismutase (150 U/ml) to the hamster cheek
      pouch restored histamine-induced increases in venular leaky sites and clearance
      of FITC-dextran-70K during infusion of nicotine. Thus nicotine alters agonist
      induced increases in microvascular permeability, via the formation of oxygen
      radicals, to presumably inactivate nitric oxide.

PMID- 9572804
TI  - Inhibition of nitric oxide synthase slows heart rate recovery from cholinergic
      activation.
AB  - The role of nitric oxide (NO) in the cholinergic regulation of heart rate (HR)
      recovery from an aspect of simulated exercise was investigated in atria isolated
      from guinea pig to test the hypothesis that NO may be involved in the cholinergic
      antagonism of the positive chronotropic response to adrenergic stimulation.
      Inhibition of NO synthesis with NG-monomethyl-L-arginine (L-NMMA, 100 micro M)
      significantly slowed the time course of the reduction in HR without affecting the
      magnitude of the response elicited by bath-applied ACh (100 nM) or vagal nerve
      stimulation (2 Hz). The half-times (t1/2) of responses were 3.99 +/- 0.41 s in
      control vs. 7. 49 +/- 0.68 s in L-NMMA (P < 0.05). This was dependent on prior
      adrenergic stimulation (norepinephrine, 1 micro M). The effect of L-NMMA was
      reversed by L-arginine (1 mM; t1/2 4.62 +/- 0.39 s). The calcium-channel
      antagonist nifedipine (0.2 micro M) also slowed the kinetics of the reduction in
      HR caused by vagal nerve stimulation. However, the t1/2 for the reduction in HR
      with antagonists (2 mM Cs+ and 1 micro M ZD-7288) of the hyperpolarization
      activated current were significantly faster compared with control. There was no
      additional effect of L-NMMA or L-NMMA+L-arginine on vagal stimulation in groups
      treated with nifedipine, Cs+, or ZD-7288. We conclude that NO contributes to the
      cholinergic antagonism of the positive cardiac chronotropic effects of adrenergic
      stimulation by accelerating the HR response to vagal stimulation. This may
      involve an interplay between two pacemaking currents (L-type calcium channel
      current and hyperpolarization-activated current). Whether NO modulates the vagal
      control of HR recovery from actual exercise remains to be determined.

PMID- 9572805
TI  - Leukocyte adhesion molecule expression during intense resistance exercise.
AB  - We hypothesized that expression of L-selectin and very late antigen-4 (VLA-4)
      integrin adhesion molecules would influence cell type-specific redistribution
      during exercise. Women subjects performed six sets of 10-repetition maximum
      squats. L-selectin and VLA-4 integrin were measured by using flow cytometry pre-
      and postexercise on peripheral blood neutrophils and lymphocytes (n = 29
      subjects) and lymphocyte subsets (n = 70 subjects), respectively. Neutrophil
      concentration increased 41.8% (P < 0.001), whereas the percent expressing L
      selectin was unchanged (79%). Lymphocyte concentration increased 61.8% (P <
      0.001). The percent of T cells expressing L-selectin decreased from 73.5 +/- 8.9
      to 68.2 +/- 11.4% (P < 0.001); the combined population of natural killer and B
      cells expressing L-selectin decreased from 80.4 +/- 22.5 to 62.7 +/- 25.8% (P <
      0.001). VLA-4 integrin was expressed by nearly all lymphocytes both pre- and
      postexercise. The proportional decrease in L-selectin positive cells could have
      resulted from 1) shedding of L-selectin, 2) selective entry of L-selectin
      negative subsets, or 3) selective removal of L-selectin-positive subsets.

PMID- 9572806
TI  - Effect of platelet-activating factor-receptor antagonism on endotoxin-induced
      lung dysfunction in sheep.
AB  - To further define the role of platelet-activating factor (PAF) in endotoxin
      induced lung dysfunction, we examined the effect of ABT-299, a specific and
      potent PAF-receptor antagonist, on the response to endotoxemia in six chronically
      instrumented awake sheep. We administered Escherichia coli endotoxin (0.5
      microg/kg) intravenously with or without pretreatment with ABT-299 while
      monitoring mean pulmonary arterial pressure (Ppa), mean systemic arterial
      pressure (Psa), dynamic compliance of the lungs (Cdyn), and functional residual
      capacity (FRC). Endotoxin administration caused pulmonary hypertension, reduced
      Cdyn, leukopenia, and hypoxemia while having no significant effect on Psa or FRC.
      Administration of ABT-299 did not affect any of the measured variables at
      baseline. Pretreatment with ABT-299 attenuated the peak Ppa seen after endotoxin
      administration but had minimal effects on endotoxin-induced changes in Cdyn,
      white blood cell count, or alveolar-to-arterial oxygen difference. ABT-299 was
      shown to completely block the pulmonary hypertension and reduction in Cdyn seen
      after intravenous administration of exogenous PAF. We conclude that PAF does not
      play an essential role in the sheep's response to endotoxin.

PMID- 9572807
TI  - Lymphocyte subsets and adhesion molecules expression in heatstroke and heat
      stress.
AB  - We examined the specificity of the recently reported alterations in circulating
      lymphocytes in heatstroke by determining lymphocyte subsets in 14 consecutive
      heatstroke patients before and after cooling and in 7 heat-stressed controls
      using single- or two-color immunofluorescence flow cytometry. The relationship
      with catecholamine levels was also studied. In heatstroke, percentages of T
      (CD3(+)/CD19(-)), T-helper (CD4(+)/CD8(-)), T-inactive [CD3(+)/human leukocyte
      antigen-DR-], CD11a+, CD11c+, and CD44(+) lymphocytes were significantly
      decreased, whereas percentages of T-suppressor-cytotoxic (CD8(+)/CD4(-)), natural
      killer (NK; CD3(-)/CD16(+) or CD56(+)), CD3(+)/CD16(+) or CD56(+), and CD54(+)
      lymphocytes were significantly increased, compared with 11 normal controls. The
      changes in the absolute numbers of lymphocyte subsets were in the same direction
      and were significant for T-helper, T-suppressor-cytotoxic, NK, CD3(+)/CD16(+) or
      CD56(+), and CD11c+ lymphocytes. Milder but significant changes in percentages of
      T-helper, T-suppressor-cytotoxic, CD11c+, and CD44(+) lymphocytes were seen in
      heat stress. Cooling was associated with partial or complete normalization,
      further derangement (CD11a+, CD11c+), or overcorrection (NK, T-suppressor
      cytotoxic, CD11b+) of abnormal percentages of lymphocyte subsets. Norepinephrine
      levels were significantly elevated in heatstroke (4.7-fold) and heat stress (3.2
      fold), but did not significantly correlate with lymphocyte subsets. We conclude
      that heatstroke is associated with significant changes in percentages and in
      absolute numbers of a wide range of circulating lymphocyte subsets that are not
      related to elevated catecholamine levels or totally normalized by cooling.
      Similar, albeit milder, changes are seen in heat stress, suggesting that the two
      syndromes represent a continuum.

PMID- 9572808
TI  - Patent foramen ovale and decompression sickness in sports divers.
AB  - Patency of the foramen ovale (PFO) may be a cause of unexplained decompression
      sickness (DCS) in sports divers. To assess the relationship between PFO and DCS,
      a case-control study was undertaken in a population of Belgian sports divers.
      Thirty-seven divers who suffered from neurological DCS were compared with matched
      control divers who never had DCS. All divers were investigated with
      transesophageal contrast echocardiography for the presence of PFO. PFO size was
      semiquantified on the basis of the amount of contrast passage. Divers with DCS
      with lesions localized in the high cervical spinal cord, cerebellum, inner ear
      organs, or cerebrum had a significantly higher prevalence of PFO than divers with
      DCS localizations in the lower spinal cord. For unexplained DCS (DCS without
      commission of any diving procedural errors), this difference was significant for
      large PFOs only. We conclude that PFO plays a significant role in the occurrence
      of unexplained cerebral DCS, but not of spinal DCS. We further stress the
      importance of standardization and semiquantification of future PFO studies that
      use transesophageal contrast echocardiography.

PMID- 9572809
TI  - Effect of carbohydrate ingestion on adipose tissue lipolysis during long-lasting
      exercise in trained men.
AB  - To study whether sucrose administration acts on lipid mobilization during
      prolonged exercise, we used subcutaneous abdominal adipose tissue microdialysis
      in eight well-trained subjects submitted at random to two 100-min exercises (50%
      maximal aerobic power) on separate days. After 50 min of exercise, the subjects
      ingested either a sucrose solution (0.75 g/kg body wt) or water. By using a
      microdialysis probe, dialysate was obtained every 10 min from the subjects at
      rest, during exercise, and during a 30-min recovery period. During exercise
      without sucrose, plasma and dialysate glycerol increased significantly. With
      sucrose, the response was significantly lower for dialysate glycerol (P < 0.05).
      Plasma free fatty acid level was lower after sucrose than after water ingestion
      (P < 0.05). With water ingestion, plasma catecholamines increased significantly,
      whereas insulin fell (P < 0.05). With sucrose ingestion, the epinephrine response
      was blunted, whereas the insulin level was significantly increased. In
      conclusion, the use of adipose tissue microdialysis directly supports a lower
      lipid mobilization during exercise when sucrose is supplied, which confirms that
      the availability of carbohydrate influences lipid mobilization.

PMID- 9572810
TI  - L-arginine-NO pathway and CNS oxygen toxicity.
AB  - The involvement of the L-arginine-nitric oxide (NO) pathway in the pathogenesis
      of hyperoxia-induced seizures was studied by using agents controlling NO levels.
      We selected two inhibitors of nitric oxide synthase, the systemic inhibitor
      Nomega-nitro-L-arginine methyl ester (L-NAME) and the novel cerebral-specific
      inhibitor 7-nitroindazole, and two generators of NO, the NO donor S-nitroso-N
      acetylpenicillamine and the physiological precursor L-arginine. Rats with chronic
      cortical electrodes were injected intraperitoneally with different doses of one
      of the agents or their vehicles before exposure to 0.5 MPa O2 and O2 with 5% CO2
      at an absolute pressure of 0.5 MPa. The duration of the latent period until the
      onset of electrical discharges in the electroencephalogram was used as an index
      of central nervous system O2 toxicity. The two nitric oxide synthase inhibitors L
      NAME and 7-nitroindazole significantly prolonged the latent period to the onset
      of seizures on exposure to both hyperbaric O2 and to the hypercapnic-hyperoxic
      mixture. Pretreatment with the NO donor S-nitroso-N-acetylpenicillamine
      significantly shortened the latent period, whereas L-arginine, the physiological
      precursor of NO, significantly prolonged the latent period to onset of seizures.
      Our results suggest that the L-arginine-NO pathway is involved in the
      pathophysiology of hyperoxia-induced seizures via various regulating mechanisms.

PMID- 9572811
TI  - Gravity effects on upper airway area and lung volumes during parabolic flight.
AB  - We measured upper airway caliber and lung volumes in six normal subjects in the
      sitting and supine positions during 20-s periods in normogravity, hypergravity
      [1.8 + head-to-foot acceleration (Gz)], and microgravity ( approximately 0 Gz)
      induced by parabolic flights. Airway caliber and lung volumes were inferred by
      the acoustic reflection method and inductance plethysmography, respectively. In
      subjects in the sitting position, an increase in gravity from 0 to 1. 8 +Gz was
      associated with increases in the calibers of the retrobasitongue and
      palatopharyngeal regions (+20 and +30%, respectively) and with a concomitant 0.5
      liter increase in end-expiratory lung volume (functional residual capacity, FRC).
      In subjects in the supine position, no changes in the areas of these regions were
      observed, despite significant decreases in FRC from microgravity to normogravity
      (-0.6 liter) and from microgravity to hypergravity (-0.5 liter). Laryngeal
      narrowing also occurred in both positions (about -15%) when gravity increased
      from 0 to 1.8 +Gz. We concluded that variation in lung volume is insufficient to
      explain all upper airway caliber variation but that direct gravity effects on
      tissues surrounding the upper airway should be taken into account.

PMID- 9572812
TI  - Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats.
AB  - Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is elevated in
      the right heart and plasma of hypoxia-adapted rats. To test the hypothesis that
      BNP protects against hypoxic pulmonary hypertension, we measured right
      ventricular systolic pressure (RVSP), right ventricle (RV) weight-to-body weight
      (BW) ratio (RV/BW), and percent muscularization of peripheral pulmonary vessels
      (%MPPV) in rats given an intravenous infusion of BNP, atrial natriuretic peptide
      (ANP), or saline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm).
      Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did
      normoxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 micro
      g/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV. Under
      hypoxic conditions, low-rate BNP infusion (0.2 micro g/h) had no effect on plasma
      BNP or on severity of pulmonary hypertension. However, high-rate BNP infusion
      (1.4 micro g/h) increased plasma BNP (69 +/- 8 vs. 35 +/- 4 pg/ml, P < 0.05),
      lowered RV/BW (0.87 +/- 0.05 vs. 1.02 +/- 0.04, P < 0.05), and decreased %MPPV
      (60 vs. 74%, P < 0.05). There was also a trend toward lower RVSP (55 +/- 3 vs. 64
      +/- 2, P = not significant). Infusion of ANP at 1.4 micro g/h increased plasma
      ANP in hypoxic rats (759 +/- 153 vs. 393 +/- 54 pg/ml, P < 0.05) but had no
      effect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary
      vascular responses to hypoxia and, at the doses used in this study, is more
      effective than ANP at blunting pulmonary hypertension during the first 2 wk of
      hypoxia.

PMID- 9572813
TI  - Effects of hepatic portal infusion of deionized water on metabolic and hormonal
      responses to exercise in rats.
AB  - The present study was conducted to investigate the in vivo effects of an
      intrahepatic infusion of deionized water during exercise in rats.
      Adrenodemedullated male Sprague-Dawley rats were continuously infused for 30 min
      either at rest or during treadmill exercise (26 m/min, 0% grade). Rats were
      randomly assigned to one of three infusion conditions (52 micro ul/min) with
      either deionized water (PW) or saline (PS; NaCl; 0.9%) via the hepatic portal
      vein or deionized water through the jugular vein (JW). The exercise period caused
      a significant (P < 0.05) decrease in liver glycogen and relative liver water
      content and peripheral and portal blood glucose and insulin while increasing
      peripheral and portal glucagon and K+ plasma concentrations. These responses,
      with the exception of K+, were not influenced by the different types of
      infusions. The increase in K+ during exercise was significantly (P < 0.05) higher
      in JW rats than in the PW and PS groups. Both the infusion and exercise protocols
      did not significantly alter the liver weight-to-body weight ratio, plasma
      osmolality, free fatty acids, beta-hydroxybutyrate, Na+, Cl-, vasopressin, and
      catecholamine concentrations. It is concluded that an hepatic portal infusion of
      deionized water does not specifically alter the metabolic and hormonal responses
      to exercise in rats.

PMID- 9572814
TI  - Regulation of glucose transporters GLUT-4 and GLUT-1 gene transcription in
      denervated skeletal muscle.
AB  - Because GLUT-4 expression is decreased whereas GLUT-1 expression is increased in
      denervated skeletal muscle, we examined the effects of denervation on GLUT-4 and
      GLUT-1 gene transcription. The right hindlimb skeletal muscle of male transgenic
      mice containing sequential truncations (2,400, 1,639, 1,154, and 730 bp) of the
      human GLUT-4 promoter linked to the chloramphenacol acyl transferase (CAT) gene
      was denervated, and the contralateral hindlimb was sham operated. RNase
      protection analysis revealed that after 72 h denervation decreased CAT mRNA and
      GLUT-4 mRNA levels 64-85%, respectively (P < 0.05), in the gastrocnemius muscles.
      In contrast, denervation of the right hindlimb of male rats increased GLUT-1 gene
      transcription and GLUT-1 mRNA levels by 94 and 213%, respectively (P < 0.05). In
      conclusion, GLUT-4 transcription is decreased but GLUT-1 transcription is
      increased in denervated skeletal muscle, suggesting that the effects of
      denervation on GLUT-4 and GLUT-1 expression are, in part, transcriptionally
      mediated. Furthermore, these data indicate that a DNA sequence regulated by
      denervation is located within 730 bp of the 5'-flanking promoter region of the
      human GLUT-4 gene.

PMID- 9572815
TI  - Effect of creatine supplementation on sprint exercise performance and muscle
      metabolism.
AB  - The aim of the present study was to examine the effect of creatine
      supplementation (CrS) on sprint exercise performance and skeletal muscle
      anaerobic metabolism during and after sprint exercise. Eight active, untrained
      men performed a 20-s maximal sprint on an air-braked cycle ergometer after 5 days
      of CrS [30 g creatine (Cr) + 30 g dextrose per day] or placebo (30 g dextrose per
      day). The trials were separated by 4 wk, and a double-blind crossover design was
      used. Muscle and blood samples were obtained at rest, immediately after exercise,
      and after 2 min of passive recovery. CrS increased the muscle total Cr content
      (9.5 +/- 2.0%, P < 0.05, mean +/- SE); however, 20-s sprint performance was not
      improved by CrS. Similarly, the magnitude of the degradation or accumulation of
      muscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate,
      lactate, and glycogen) and plasma metabolites (e.g. , lactate, hypoxanthine, and
      ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These
      data demonstrated that CrS increased muscle total Cr content, but the increase
      did not induce an improved sprint exercise performance or alterations in
      anaerobic muscle metabolism.

PMID- 9572816
TI  - Intramuscular fatty acid metabolism evaluated with stable isotopic tracers.
AB  - We evaluated the applicability of stable isotopic tracers to the study of
      intramuscular fatty acid metabolism by infusing both [U-13C]palmitate and [1
      13C]oleate intravenously for 4 h into fasted conscious rats. Skeletal muscles
      were sequentially biopsied, and the concentration and 13C enrichment of fatty
      acids were measured by gas chromatography/combustion/isotope ratio mass
      spectrometry. Throughout the study, the 13C enrichment of plasma palmitate and
      oleate remained substantially greater than intramuscular nonesterified palmitate
      and oleate enrichment, which in turn was greater than intramuscular triglyceride
      palmitate and oleate enrichment. Fractional synthesis rates of intramuscular
      triglycerides in gastrocnemius and soleus were 0.267 +/- 0.075 and 0. 100 +/-
      0.030/h (P = 0.04), respectively, as determined by using [U-13C]palmitate, and
      were 0.278 +/- 0.049 and 0.075 +/- 0.013/h (P = 0.02), respectively, by using [1
      13C]oleate. We conclude that plasma free fatty acids are a source for
      intramuscular triglycerides and nonesterified fatty acids; the latter are likely
      the synthetic precursors of the former. Uniformly and singly labeled [13C]fatty
      acid tracers will provide an important tool to study intramuscular fatty acid and
      triglyceride metabolism.

PMID- 9572817
TI  - Repeated measurements of airway and parenchymal mechanics in rats by using low
      frequency oscillations.
AB  - For studies investigating the mechanisms underlying the development of allergic
      conditions such as asthma, noninvasive methodologies for separating airway and
      parenchymal mechanics in animal models are required. To develop such a method,
      seven Brown Norway rats were studied on three occasions over a 14-day period.
      After the baseline measurements, on the third day inhaled methacholine was
      administered. Once lung function returned to the baseline level, a thoracotomy
      was performed to compare the lung mechanics in the intact- and open-chest
      conditions. On each occasion, the rats were anesthetized, paralyzed, and
      intubated. Small-amplitude oscillations between 0.5 and 21 Hz were applied
      through a wave tube to obtain respiratory impedance (Zrs). Esophageal pressure
      was measured to separate Zrs into pulmonary (ZL) and chest wall (Zw) components.
      A model containing a frequency-independent resistance and inertance and a tissue
      component, including tissue damping and elastance, was fitted to Zrs, ZL, and Zw
      spectra. Measurements of Zrs, ZL, or Zw and the model parameters calculated from
      them did not differ among tests. The number of animals required to show group
      changes in lung mechanics was significantly lower when animals were measured
      noninvasively than when the group changes were calculated from open-chest
      measurements. In conclusion, the method reported in this study can be used to
      separate airway and lung tissue mechanics noninvasively over a series of tests
      and can detect pulmonary constrictor responses for the airways and the parenchyma
      separately.

PMID- 9572818
TI  - Muscle metabolites and performance during high-intensity, intermittent exercise.
AB  - Six men were studied during four 30-s "all-out" exercise bouts on an air-braked
      cycle ergometer. The first three exercise bouts were separated by 4 min of
      passive recovery; after the third bout, subjects rested for 4 min, exercised for
      30 min at 30-35% peak O2 consumption, and rested for a further 60 min before
      completing the fourth exercise bout. Peak power and total work were reduced (P <
      0. 05) during bout 3 [765 +/- 60 (SE) W; 15.8 +/- 1.0 kJ] compared with bout 1
      (1,168 +/- 55 W, 23.8 +/- 1.2 kJ), but no difference in exercise performance was
      observed between bouts 1 and 4 (1,094 +/- 64 W, 23.2 +/- 1.4 kJ). Before bout 3,
      muscle ATP, creatine phosphate (CP), glycogen, pH, and sarcoplasmic reticulum
      (SR) Ca2+ uptake were reduced, while muscle lactate and inosine 5'-monophosphate
      were increased. Muscle ATP and glycogen before bout 4 remained lower than values
      before bout 1 (P < 0.05), but there were no differences in muscle inosine 5'
      monophosphate, lactate, pH, and SR Ca2+ uptake. Muscle CP levels before bout 4
      had increased above resting levels. Consistent with the decline in muscle ATP
      were increases in hypoxanthine and inosine before bouts 3 and 4. The decline in
      exercise performance does not appear to be related to a reduction in muscle
      glycogen. Instead, it may be caused by reduced CP availability, increased H+
      concentration, impairment in SR function, or some other fatigue-inducing agent.

PMID- 9572819
TI  - Cervical magnetic stimulation as a method to discriminate between diaphragm and
      rib cage muscle fatigue.
AB  - Inspiratory muscle fatigue can probably determine hypercapnic respiratory
      failure. Diaphragm fatigue is detected by electrical phrenic stimulation (ELS),
      but there is no simple tool to assess rib cage muscle (RCM) fatigue. Cervical
      magnetic stimulation (CMS) costimulates the phrenic nerves and RCM. We reasoned
      that changes in transdiaphragmatic pressure twitch (Pdi,tw) with CMS and ELS
      should be different after selective diaphragm vs. RCM fatigue. Five volunteers
      performed inspiratory resistive tasks while voluntarily uncoupling diaphragm and
      RCM. Baseline Pdi,twELS and Pdi,twCMS were 28.57 +/- 1.68 and 32.83 +/- 2.92
      cmH2O. After selective diaphragm loading, Pdi,twELS and Pdi,twCMS were reduced by
      39 and 26%, with comparable decreases in gastric pressure twitch (Pga,tw).
      Esophageal pressure twitch (Pes,tw) was better preserved with CMS. Therefore
      Pes,tw/Pga,tw was lower with ELS than CMS (-1.24 +/- 0.16 vs. -1.73 +/- 0.11, P =
      0.05). After selective RCM loading, there was no diaphragm fatigue, but Pes,twCMS
      was significantly reduced (-30%). These findings support the role of rib cage
      stiffening by CMS-related RCM contraction in the ELS-CMS differences and suggest
      that CMS can be used to assess RCM fatigue.

PMID- 9572820
TI  - Breathing route dependence of upper airway muscle activity during hyperpnea.
AB  - Exercise (Ex) and hypercapnia (HC) both lead to increases in ventilation and
      upper airway muscle (UAM) activity. To determine whether different breathing
      routes (nasal vs. oral) or stimuli produced differential UAM activation,
      electromyographic (EMG) activity of the alae nasi (AN) and genioglossus (GG) were
      measured in seven normal subjects seated on a bicycle ergometer. Subjects
      performed paired runs during both progressive Ex and HC while breathing through
      the nose alone (N) or the mouth alone (O). During hyperpnea, AN EMG was greater
      when the subjects were breathing via N [81 +/- 6% maximum (HC) and 69 +/- 7%
      maximum (Ex)] than when they were breathing via O [30 +/- 5% maximum (HC) and 27
      +/- 5% maximum (Ex); both P < 0.01], whereas the GG EMG did not differ between N
      and O. Both AN and GG EMG were similar for Ex and HC when the subjects were
      breathing via the same route. We conclude that UAM activation was independent of
      the nature of the stimulus. However, the AN muscle but not the GG muscle
      demonstrated breathing-route dependence of activity.

PMID- 9572821
TI  - Abdominal motor unit activity during respiratory and nonrespiratory tasks.
AB  - Abdominal muscles serve multiple roles, but the functional organization of their
      motoneurons remains unclear. To gain insight, we recorded single motor unit
      potentials from the internal oblique (IO) and transversus abdominis (TA) muscles
      of three standing subjects during quiet breathing, a leg lift, and an expiratory
      threshold load. Inspiratory airflow, recorded from a pneumotachometer, provided
      tidal volumes and respiratory cycle timing. Fine wires, implanted under
      ultrasonic imaging, detected single motor unit potentials that were visually
      distinguished by their spike morphology. From the number of spikes, firing
      profiles, times of occurrence in the respiratory cycle, and their onset,
      instantaneous, mean, and peak firing frequencies we deduced that 1) breathing
      patterns varied across tasks, 2) different motor units were recruited for each
      task with essentially no overlap, 3) their firing displayed prominent expiratory
      activity during each task, and 4) the recruitment levels and discharge patterns
      of IO and TA were different. We conclude that the IO and TA motor pools receive a
      strong central respiratory drive, yet each pool receives its own distinct, task
      dependent synaptic input.

PMID- 9572822
TI  - Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats.
AB  - Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase
      in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81:
      2509-2516, 1996). In that study, the increase in IGF-I was found to precede
      measurable increases in muscle protein and was correlated with an increase in
      muscle DNA content. The present study was undertaken to test the hypothesis that
      direct IGF-I infusion would result in an increase in muscle DNA as well as in
      various measurements of muscle size. Either 0.9% saline or nonsystemic doses of
      IGF-I were infused directly into a non-weight-bearing muscle of rats, the
      tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous
      miniosmotic pump. Saline infusion had no effect on the mass, protein content, or
      DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart
      weight. The absolute weight of the infused TA muscles was approximately 9%
      greater (P < 0.05) than that of the contralateral TA muscles. IGF-I infusion
      resulted in significant increases in the total protein and DNA content of TA
      muscles (P < 0.05). As a result of these coordinated changes, the DNA-to-protein
      ratio of the hypertrophied TA was similar to that of the contralateral muscles.
      These results suggest that IGF-I may be acting to directly stimulate processes
      such as protein synthesis and satellite cell proliferation, which result in
      skeletal muscle hypertrophy.

PMID- 9572823
TI  - Effect of prolonged heavy exercise on pulmonary gas exchange in horses.
AB  - During short-term maximal exercise, horses have impaired pulmonary gas exchange,
      manifested by diffusion limitation and arterial hypoxemia, without marked
      ventilation-perfusion (VA/Q) inequality. Whether gas exchange deteriorates
      progressively during prolonged submaximal exercise has not been investigated. Six
      thoroughbred horses performed treadmill exercise at approximately 60% of maximal
      oxygen uptake until exhaustion (28-39 min). Multiple inert gas, blood-gas,
      hemodynamic, metabolic rate, and ventilatory data were obtained at rest and 5-min
      intervals during exercise. Oxygen uptake, cardiac output, and alveolar-arterial
      PO2 gradient were unchanged after the first 5 min of exercise. Alveolar
      ventilation increased progressively during exercise, from increased tidal volume
      and respiratory frequency, resulting in an increase in arterial PO2 and decrease
      in arterial PCO2. At rest there was minimal VA/Q inequality, log SD of the
      perfusion distribution (log SDQ) = 0.20. This doubled by 5 min of exercise (log
      SDQ = 0.40) but did not increase further. There was no evidence of alveolar-end
      capillary diffusion limitation during exercise. However, there was evidence for
      gas-phase diffusion limitation at all time points, and enflurane was
      preferentially overretained. Horses maintain excellent pulmonary gas exchange
      during exhaustive, submaximal exercise. Although VA/Q inequality is greater than
      at rest, it is less than observed in most mammals and the effect on gas exchange
      is minimal.

PMID- 9572824
TI  - Heat acclimation, aerobic fitness, and hydration effects on tolerance during
      uncompensable heat stress.
AB  - The purpose of the present study was to determine the separate and combined
      effects of aerobic fitness, short-term heat acclimation, and hypohydration on
      tolerance during light exercise while wearing nuclear, biological, and chemical
      protective clothing in the heat (40 degrees C, 30% relative humidity). Men who
      were moderately fit [(MF); <50 ml . kg-1 . min-1 maximal O2 consumption; n = 7]
      and highly fit [(HF); >55 ml . kg-1 . min-1 maximal O2 consumption; n = 8] were
      tested while they were euhydrated or hypohydrated by approximately 2.5% of body
      mass through exercise and fluid restriction the day preceding the trials. Tests
      were conducted before and after 2 wk of daily heat acclimation (1-h treadmill
      exercise at 40 degrees C, 30% relative humidity, while wearing the nuclear,
      biological, and chemical protective clothing). Heat acclimation increased sweat
      rate and decreased skin temperature and rectal temperature (Tre) in HF subjects
      but had no effect on tolerance time (TT). MF subjects increased sweat rate but
      did not alter heart rate, Tre, or TT. In both MF and HF groups, hypohydration
      significantly increased Tre and heart rate and decreased the respiratory exchange
      ratio and the TT regardless of acclimation state. Overall, the rate of rise of
      skin temperature was less, while DeltaTre, the rate of rise of Tre, and the TT
      were greater in HF than in MF subjects. It was concluded that exercise-heat
      tolerance in this uncompensable heat-stress environment is not influenced by
      short-term heat acclimation but is significantly improved by long-term aerobic
      fitness.

PMID- 9572825
TI  - Hypoproteinemia, strong-ion difference, and acid-base status in critically ill
      patients.
AB  - The present study was a prospective, nonrandomized, observational examination of
      the relationship among hypoproteinemia and electrolyte and acid-base status in a
      critical care population of patients. A total of 219 arterial blood samples
      reviewed from 91 patients was analyzed for arterial blood gas, electrolytes,
      lactate, and total protein. Plasma strong-ion difference ([SID]) was calculated
      from [Na+] + [K+] - [Cl-] - [La-]. Total protein concentration was used to derive
      the total concentration of weak acid ([A]tot). [A]tot encompassed a range of 18.7
      to 9.0 meq/l, whereas [SID] varied from 48.1 to 26.6 meq/l and was directly
      correlated with [A]tot. The decline in [SID] was primarily attributable to an
      increase in [Cl-]. A direct correlation was also noted between PCO2 and [SID],
      but not between PCO2 and [A]tot. The decrease in [SID] and PCO2 was such that
      neither [H+] nor [HCO-3] changed significantly with [A]tot.

PMID- 9572826
TI  - Chronic exposure to ozone causes tolerance to airway hyperresponsiveness in
      guinea pigs: lack of SOD role.
AB  - Tolerance to respiratory effects of O3 has been demonstrated for anatomic and
      functional changes, but information about tolerance to O3-induced airway
      hyperresponsiveness (AHR) is scarce. In guinea pigs exposed to air or O3 (0.3
      parts/million, 4 h/day, for 1, 3, 6, 12, 24, or 48 days, studied 16-18 h later),
      pulmonary insufflation pressure changes induced by intravenous substance P (SP,
      0.032-3.2 micro ug/kg) were measured, then the animals were subjected to
      bronchoalveolar lavage (BAL). Bronchial rings with or without phosphoramidon were
      also evaluated 3 h after air or a single O3 exposure. O3 caused in vivo AHR
      (increased sensitivity) to SP after 1, 3, 6, 12, and 24 days of exposure compared
      with control. However, after 48 days of exposure, O3 no longer caused AHR. Total
      cell, macrophage, neutrophil, and eosinophil counts in BAL were increased in most
      O3-exposed groups. When data from all animals were pooled, we found a highly
      significant correlation between degree of airway responsiveness and total cells
      (r = 0.55), macrophages (r = 0.54), neutrophils (r = 0.47), and eosinophils (r =
      0.53), suggesting that airway inflammation is involved in development of AHR to
      SP. Superoxide dismutase (SOD) levels in BAL fluids were increased (P < 0.05)
      after 1, 3, 6, and 12 days of O3 exposure and returned to basal levels after 24
      and 48 days of exposure. O3 failed to induce hyperresponsiveness to SP in
      bronchial rings, and phosphoramidon increased responses to SP in air- and O3
      exposed groups, suggesting that neutral endopeptidase inactivation was not
      involved in O3-induced AHR to SP in vivo. We conclude that chronic exposure to 0.
      3 ppm O3, a concentration found in highly polluted cities, resulted in tolerance
      to AHR to SP in guinea pigs by an SOD-independent mechanism.

PMID- 9572827
TI  - Head-down-tilt bed rest alters forearm vasodilator and vasoconstrictor responses.
AB  - To test the hypothesis that head-down-tilt bed rest (HDBR) for 14 days alters
      vascular reactivity to vasodilatory and vasoconstrictor stimuli, the reactive
      hyperemic forearm blood flow (RHBF, measured by venous occlusion plethysmography)
      and mean arterial pressure (MAP, measured by Finapres) responses after 10 min of
      circulatory arrest were measured in a control trial (n = 20) and when sympathetic
      discharge was increased by a cold pressor test (RHBF + cold pressor test; n =
      10). Vascular conductance (VC) was calculated (VC = RHBF/MAP). In the control
      trial, peak RHBF at 5 s after circulatory arrest (34.1 +/- 2.5 vs. 48.9 +/- 4.3
      ml . 100 ml-1 . min-1) and VC (0.34 +/- 0.02 vs. 0.53 +/- 0.05 ml . 100 ml-1 .
      min-1 . mmHg-1) were reduced in the post- compared with the pre-HDBR tests (P <
      0. 05). Total excess RHBF over 3 min was diminished in the post- compared with
      the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). The ability of the cold
      pressor test to lower forearm blood flow was less in the post- than in the pre
      HDBR test (P < 0.05), despite similar increases in MAP. These data suggest that
      regulation of vascular dilation and the interaction between dilatory and
      constrictor influences were altered with bed rest.

PMID- 9572828
TI  - New in situ mouse model to quantify alveolar epithelial fluid clearance.
AB  - Because the availability of transgenic mice makes it possible to examine the
      contribution of single genes to in vivo function, we developed a simple in situ
      mouse model that can be used to quantify isosmolar alveolar epithelial fluid
      clearance (AFC). Mice were killed, a tracheostomy was done, and then a test
      solution of a 5% isosmolar albumin solution with 0.1 micro Ci of 125I-labeled
      albumin was instilled via the trachea into the distal air spaces of both lungs.
      After instillation, the lungs were inflated to 7 cmH2O with 100% O2 and
      maintained at 37 degrees C by placing the animals under an infrared lamp. AFC was
      measured by the progressive increase in concentration of labeled and unlabeled
      protein over 1 h. The results indicated the following. 1) Basal, unstimulated AFC
      in mouse lungs was significantly faster than in ex vivo rat lungs (27 +/- 5% in
      in situ mice vs. 11 +/- 3% in ex vivo rat lungs; P < 0.05). 2) Comparison of
      equivalent doses (10(-4) M) of beta-adrenergic agonist (isoproterenol) and beta2
      adrenergic agonists (terbutaline and salmeterol) indicated that stimulated
      clearance occurred only in presence of isoproterenol. 3) Because atenolol, a
      specific beta1-antagonist, abolished the effect of isoproterenol, the beta
      adrenergic stimulation appears to be mediated by beta1-receptors. The rate of AFC
      in nonperfused mouse lungs was significantly faster than in prior studies of
      nonperfused lungs in rats and sheep. Interestingly, the stimulated clearance rate
      in mice was similar to the fast rates of AFC that we recently reported in
      patients recovering from hydrostatic pulmonary edema. This in situ model is a
      unique experimental preparation that can be readily used to quantify isosmolar
      epithelial fluid clearance in mice.

PMID- 9572829
TI  - Altered metabolic response of iron-depleted nonanemic women during a 15-km time
      trial.
AB  - In this double-blinded study, 37 women with iron depletion without anemia (age 19
      36 yr) were randomly assigned to receive either an iron supplement (135 mg/day)
      or a placebo. Endurance capacity was assessed during a 15-km simulated time trial
      (TT) on a cycle ergometer before and after the 8-wk treatment. After the
      treatment, although the iron-supplemented group did not have shorter time to
      finish the TT (time), it had 2.0 kJ/min lower energy expenditure and 5.1% lower
      fractional utilization of peak oxygen consumption during the TT compared with the
      placebo group, after controlling for work rate (P < 0.05). Time, fractional
      utilization of peak oxygen consumption, and plasma lactate concentration at the
      5th km of the TT were all negatively associated with hemoglobin levels, after
      controlling for work rate (P < 0.05). In conclusion, repletion of iron stores to
      women with iron depletion without anemia increased their energetic efficiency,
      and oxygen transport capacity of the blood was found to be an important
      determinant of endurance capacity and energy metabolism in nonanemic women.

PMID- 9572830
TI  - Velocity, force, power, and Ca2+ sensitivity of fast and slow monkey skeletal
      muscle fibers.
AB  - In this study, we determined the contractile properties of single chemically
      skinned fibers prepared from the medial gastrocnemius (MG) and soleus (Sol)
      muscles of adult male rhesus monkeys and assessed the effects of the spaceflight
      living facility known as the experiment support primate facility (ESOP). Muscle
      biopsies were obtained 4 wk before and immediately after an 18-day ESOP sit, and
      fiber type was determined by immunohistochemical techniques. The MG slow type I
      fiber was significantly smaller than the MG type II, Sol type I, and Sol type II
      fibers. The ESOP sit caused a significant reduction in the diameter of type I and
      type I/II (hybrid) fibers of Sol and MG type II and hybrid fibers but no shift in
      fiber type distribution. Single-fiber peak force (mN and kN/m2) was similar
      between fiber types and was not significantly different from values previously
      reported for other species. The ESOP sit significantly reduced the force (mN) of
      Sol type I and MG type II fibers. This decline was entirely explained by the
      atrophy of these fiber types because the force per cross-sectional area (kN/m2)
      was not altered. Peak power of Sol and MG fast type II fiber was 5 and 8.5 times
      that of slow type I fiber, respectively. The ESOP sit reduced peak power by 25
      and 18% in Sol type I and MG type II fibers, respectively, and, for the former
      fiber type, shifted the force-pCa relationship to the right, increasing the Ca2+
      activation threshold and the free Ca2+ concentration, eliciting half-maximal
      activation. The ESOP sit had no effect on the maximal shortening velocity (Vo) of
      any fiber type. Vo of the hybrid fibers was only slightly higher than that of
      slow type I fibers. This result supports the hypothesis that in hybrid fibers the
      slow myosin heavy chain would be expected to have a disproportionately greater
      influence on Vo.

PMID- 9572831
TI  - Contraction-induced increase in Vmax of palmitate uptake and oxidation in
      perfused skeletal muscle.
AB  - To evaluate the effects of contractions on the kinetics of uptake and oxidation
      of palmitate in a physiological muscle preparation, rat hindquarters were
      perfused with glucose (6 mmol/l), albumin-bound [1-14C]palmitate, and varying
      amounts of albumin-bound palmitate (200-2,200 micro mol/l) at rest and during
      muscle contractions. When plotted against the unbound palmitate concentration,
      palmitate uptake and oxidation displayed simple Michaelis-Menten kinetics with
      estimated maximal velocity (Vmax) and Michaelis-Menten constant (Km) values of
      42.8 +/- 3.8 (SE) nmol . min-1 . g-1 and 13.4 +/- 3.4 nmol/l for palmitate uptake
      and 3.8 +/- 0.4 nmol . min-1 . g-1 and 8.1 +/- 2.9 nmol/l for palmitate
      oxidation, respectively, at rest. Whereas muscle contractions increased the Vmax
      for both palmitate uptake and oxidation to 91.6 +/- 10.1 and 16.5 +/- 2.3 nmol .
      min-1 . g-1, respectively, the Km remained unchanged. Vmax and Km estimates
      obtained from Hanes-Woolf plots (substrate concentration/velocity vs. substrate
      concentration) were not significantly different. In the resting perfused
      hindquarter, an increase in palmitate delivery from 31.9 +/- 0.9 to 48.7 +/- 1.2
      micro mol . g-1 . h-1 by increasing perfusate flow was associated with a decrease
      in the fractional uptake of palmitate so that the rates of uptake and oxidation
      of palmitate remained unchanged. It is concluded that the rates of uptake and
      oxidation of long-chain fatty acids (LCFA) saturate with an increase in the
      concentration of unbound LCFA in perfused skeletal muscle and that muscle
      contractions, but not an increase in plasma flow, increase the Vmax for LCFA
      uptake and oxidation. The data are consistent with the notion that uptake of LCFA
      in muscle may be mediated in part by a transport system.

PMID- 9572832
TI  - Use of nonlinear methods to assess effects of clonidine on blood pressure in
      spontaneously hypertensive rats.
AB  - In spontaneously hypertensive rats (SHR), chronic infusion of clonidine failed to
      decrease blood pressure and blood pressure variability. We used nonlinear methods
      to get a deeper insight on the effects of clonidine on blood pressure dynamics.
      For 24 h and 4 wk, clonidine (0.1 mg . kg-1 . day-1 sc) was infused by minipumps
      in the conscious SHRs, and, for comparison, a vehicle was infused in SHRs and in
      Wistar-Kyoto rats. Blood pressure was recorded for 30 min before and after
      treatments. We used the Lyapunov exponent, approximated by the inverse of the
      lmax index derived from the recurrence plot method, to characterize nonlinear
      dynamics. Before treatment, lmax index of blood pressure was lower (P < 0.01) in
      the SHRs than in the Wistar-Kyoto rats. Clonidine significantly increased lmax (P
      < 0.01) to the level observed in normotensive rats, at 24 h and up to 4 wk after
      infusion. We conclude that clonidine has a significant chronic effect on blood
      pressure dynamics, as evidenced by nonlinear methods. Our study also suggests
      that the mechanisms governing blood pressure variations are nonlinear.

PMID- 9572833
TI  - Analytic assessment of the various bioimpedance methods used to estimate body
      water.
AB  - Knowledge of patient fluid distribution would be useful clinically. Both single
      frequency (SF) and impedance modeling approaches are proposed. The high
      intercorrelation between body water compartments makes determining the best
      approach difficult. This study was conducted to evaluate the merits of an SF
      approach. Mathematical simulation was performed to determine the effect of tissue
      change on resistance and reactance. Dilution results were reanalyzed, and
      resistance and parallel reactance were used to predict the intracellular water
      for two groups. Results indicated that the amount of intracellular and
      extracellular water conduction at any SF can vary with tissue change, and
      reactance at any SF is affected by all tissue parameters. Modeling provided a
      good prediction of dilution intracellular and extracellular water, but an SF
      method did not. Intracellular, extracellular, and total body water were equally
      predicted at all frequencies by SF resistance and parallel reactance.
      Extracellular and intracellular water are best measured through modeling, because
      only at the zero and infinite frequencies are the results sensitive only to
      extracellular and intracellular water. At all other frequencies there are other
      effects.

PMID- 9572834
TI  - Adherent neutrophils activate endothelial myosin light chain kinase: role in
      transendothelial migration.
AB  - Increased vascular endothelial cell (EC) permeability and neutrophilic leukocyte
      (PMN) diapedesis through paracellular gaps are cardinal features of acute
      inflammation. Activation of the EC contractile apparatus is necessary and
      sufficient to increase vascular permeability in specific models of EC barrier
      dysfunction. However, it is unknown whether EC contraction with subsequent
      paracellular gap formation is required for PMN transendothelial migration in
      response to chemotactic factors. To test this possibility, we assessed migration
      of human PMNs across confluent bovine pulmonary arterial EC monolayers.
      Transendothelial PMN migration in the absence of a chemotactic gradient was
      minimal, whereas abluminal addition of leukotriene B4 (LTB4; 5 microM) resulted
      in significantly increased PMN migration. Reductions in EC myosin light chain
      kinase (MLCK) activity by EC monolayer pretreatment with specific MLCK inhibitors
      (KT-5926 or ML-7) or by increases in cAMP-protein kinase A activity (cholera
      toxin) significantly reduced PMN transmigration (30-70% inhibition). In contrast,
      pretreatment with the myosin-associated phosphatase inhibitor calyculin resulted
      in the accumulation of phosphorylated myosin light chains, EC contraction, and
      significantly enhanced PMN migration. Finally, the interaction of PMNs with 32P
      labeled EC monolayers was shown to directly increase EC myosin phosphorylation in
      a time-dependent fashion. Taken together, these results are consistent with the
      hypothesis that the phosphorylation status of EC myosin regulates PMN migration
      and further indicate that EC MLCK is activated by chemoattractant-stimulated
      PMNs. Neutrophil-dependent activation of the EC contractile apparatus with
      subsequent paracellular gap formation may be a key determinant of
      transendothelial PMN migration responses to chemotactic agents.

PMID- 9572835
TI  - Asymmetric cyanomet valency hybrid hemoglobin, (alpha+CN-beta+CN-)(alpha beta):
      the issue of valency exchange.
AB  - A new framework for hemoglobin cooperativity was proposed by Ackers and
      colleagues on the basis of the hyper thermodynamic stability and deoxy (T)
      quaternary structure of one of diliganded deoxy-cyanomet hybrid hemoglobins,
      (alpha+CN-beta+CN-)(alpha beta), studied by hybridization of the equimolar
      mixture of deoxyhemoglobin and cyanomethemoglobin through a long (70-100 h) dimer
      exchange reaction [Daugherty et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1110
      1114]. Recently, we reported that the published hyperstability of (alpha+CN
      beta+CN-)(alpha beta) is incorrect due to the occurrence of valency exchange
      between the heme sites of both parental hemoglobins during the long deoxy
      incubation [Shibayama et al. (1997) Biochemistry 36, 4375-4381]. We also noted a
      difficulty in maintaining both anaerobicity and excess free cyanide of the sample
      during the long incubation, which led to formation of cyanide-unbound aqometheme
      in the original deoxyhemoglobin resulting from the electron transfer to
      cyanometheme. This paper is a response to a recent argument against our work
      [Ackers et al. (1997) Biochemistry 36, 10822-10829]. Ackers et al. have claimed
      that no appreciable formation of aqomethemoglobin with their methods ensures
      their sample integrity, based on a supposition that our observed valency exchange
      may have occurred via aqometheme. In this paper, however, we demonstrate that
      appreciable (>27%) valency exchange really occurs between deoxy and cyanometheme
      sites during 72 h incubation under conditions where both anaerobicity and excess
      free cyanide of the sample solution are maintained by a continuous flow of
      humidified N2 with HCN. This confirms our view that previous experimental data on
      (alpha+CN-beta+CN-)(alpha beta) obtained by the long incubations should be
      subject to reexamination while our earlier estimation of a lower limit of free
      energy of (alpha+CN-beta+CN-)(alpha beta) (i.e., >/= -10.1 kcal/mol) by a rapid
      method (35 min) is still valid. We also suggest a possibility that the T
      quaternary structure of (alpha+CN-beta+CN-)(alpha beta) assigned by Ackers and
      colleagues using the long incubations is an artifact arising from the valency
      exchange. These results suggest that the putative mechanistic picture for
      hemoglobin cooperativity inferred from studies on deoxy-cyanomet hybrids is
      without foundation.

PMID- 9572836
TI  - DNA cassette exchange in ES cells mediated by Flp recombinase: an efficient
      strategy for repeated modification of tagged loci by marker-free constructs.
AB  - The repeated modification of a genomic locus is a technically demanding but
      powerful strategy to analyze the function of a particular gene product or the
      role of cis-regulatory DNA elements in mammalian cells. The initial step is
      "tagging" a site with a selectable marker which is done by homologous
      recombination (HR) to modify a known locus or by random integration to study cis
      regulatory elements at a reproducibly accessible genomic location. The tag is
      then used to target the construct of choice during an exchange step. Presented
      here is a novel technique in which the exchange is independent of HR and does not
      introduce vector sequences. It relies on our previous studies on the replacement
      of DNA cassettes by FLP-recombinase, whereby some common limitations can be
      overcome. To this end, the tag, a hygtk positive/negative selection marker, is
      integrated into the genome of embryonic stem (ES) cells. This marker is flanked
      by a wild-type Flp-recognition target (FRT) site on one end and by a modified
      heterospecific FRT site on the other. Successful Flp-mediated replacement of the
      hygtk cassette is enriched by ganciclovir (GANC) selection for cells that lack
      the encoded fusion protein. Thereby, the hygtk gene can be exchanged for
      virtually any sequence in a single efficient step without the need of introducing
      a positive selectable marker. The system can hence be used to analyze the
      function of either a gene product or regulatory sequences in ES cells or the
      transgenic mice derived thereof.

PMID- 9572837
TI  - Up-regulation of luciferase gene expression with antisense oligonucleotides:
      implications and applications in functional assay development.
AB  - HeLa Tet-Off cells were transfected transiently as well as stably with a
      recombinant plasmid (pLuc/705) carrying the luciferase gene interrupted by a
      mutated human beta-globin intron 2 (IVS2-705). The mutation in the intron causes
      aberrant splicing of luciferase pre-mRNA, preventing translation of luciferase.
      However, treatment of the cells with a 2'-O-methyl-oligoribonucleotide targeted
      to the aberrant splice sites induces correct splicing, restoring luciferase
      activity. The effects are sequence-specific, depend on the concentration of the
      oligonucleotide, and can be modulated by the pretreatment of the cell line,
      Luc/705, with tetracycline. Thus, the cell line provides, among others, a novel
      functional assay system superior to other procedures that are based on protein
      down-regulation. In particular, the system would be ideal in assessing the
      cellular delivery efficiency of antisense oligonucleotides.

PMID- 9572838
TI  - Agonist-dependent phosphorylation of the parathyroid hormone/parathyroid hormone
      related peptide receptor.
AB  - Native PTH/PTHrP receptors in ROS 17/2.8 cells are downregulated after PTH
      treatment. Since downregulation may involve receptor phosphorylation, we examined
      PTH/PTHrP receptor phosphorylation in ROS 17/2.8 cells and we mapped the agonist
      induced phosphorylation sites using recombinant PTH/PTHrP receptors expressed in
      LLCPK-1 and COS-7 cells. The data show that the PTH/PTHrP receptor is rapidly
      phosphorylated in ROS 17/2.8 cells with a maximum occurring at 20 min. The
      phosphorylation was dose-dependent; it occurred with PTH concentrations that are
      known to downregulate the PTH/PTHrP receptor in ROS 17/2.8 cells. The time course
      and the dose requirement for phosphorylation were similar in ROS 17/2.8 cells,
      which express native PTH/PTHrP receptors, and in LLCPK-1 cells stably transfected
      with the PTH/PTHrP receptor cDNA. PTH/PTHrP receptor phosphorylation in ROS
      17/2.8, COS-7, and LLCPK-1 cells was also stimulated with forskolin and phorbol
      myristate acetate (PMA). Additionally, in LLCPK-1 cells, which express native
      clacitonin receptors, PTH/PTHrP receptor phosphorylation was stimulated by
      calcitonin. These data suggest involvement of second messenger-stimulated kinases
      in PTH/PTHrP receptor phosphorylation. However, staurosporine, which fully
      blocked the effects of PMA, forskolin, and clacitonin, partially decreased the
      effects of PTH on PTH/PTHrP receptor phosphorylation. These data indicate
      involvement of other kinase(s) in PTH-induced PTH/PTHrP receptor phosphorylation.
      CNBr cleavage of recombinant receptors expressed in COS-7 cells combined with
      site-directed mutagenesis revealed that the phosphorylated residues of the
      PTH/PTHrP receptor map to two regions of the carboxyl-terminal tail located
      between residues A480 and M499 and residues M499 and M553. These data indicate
      that the PTH/PTHrP receptor is phosphorylated after PTH stimulation on two
      regions of the carboxyl-terminal tail and that agonist-dependent phosphorylation
      involves both staurosporine-sensitive and -insensitive kinases.

PMID- 9572839
TI  - Structure of the bis(Mg2+)-ATP-oxalate complex of the rabbit muscle pyruvate
      kinase at 2.1 A resolution: ATP binding over a barrel.
AB  - Pyruvate kinase from rabbit muscle has been cocrystallized as a complex with
      MgIIATP, oxalate, Mg2+, and either K+ or Na+. Crystals with either Na+ or K+
      belong to the space group P2(1)2(1)2(1), and the asymmetric units contain two
      tetramers. The structures were solved by molecular replacement and refined to 2.1
      (K+) and 2.35 A (Na+) resolution. The structures of the Na+ and K+ complexes are
      virtually isomorphous. Each of the eight subunits within the asymmetric unit
      contains MgIIoxalate as a bidentate complex linked to the protein through
      coordination of Mg2+ to the carboxylates of Glu 271 and Asp 295. Six of the
      subunits also contain an alpha,beta,gamma-tridentate complex of MgIIATP, and the
      active-site cleft, located between domains A and B, is closed in these subunits.
      In the remaining two subunits MgIIATP is missing, and the active-site cleft is
      open. Closure of the active-site cleft in the fully liganded subunits includes a
      rotation of 41 degrees of the B domain relative to the A domain. alpha-Carbons of
      residues in the B domain undergo movements of up to 17.8 A (Lys 124) in the cleft
      closure. Lys 206, Arg 119, and Asp 177 from the B domain move several angstroms
      from their positions in the open conformation to contact the MgIIATP complex in
      the active site. The gamma-phosphate of ATP coordinates to both magnesium ions
      and to the monovalent cation, K+ or Na+. A Mg2+-coordinated oxygen from the
      MgIIoxalate complex lies 3.0 A from Pgamma of ATP, and this oxygen is positioned
      for an in-line attack on the phosphorus. The side chains of Lys 269 and Arg 119
      are positioned to provide leaving-group activation in the forward and reverse
      directions. There is no obvious candidate for the acid/base catalyst near the 2
      si face of the prospective enolate of the normal substrate. A functional group
      linked through solvent and side-chain hydroxyls may function in a proton relay.

PMID- 9572840
TI  - Identification of unfolding domains in large proteins by their unfolding rates.
AB  - Three unfolding domains in rabbit muscle aldolase destabilized in 3 M urea have
      been identified from their unfolding rate constants (0.10, 0.036, and 0.0064 min
      1). The populations of folded and various, partially unfolded forms were
      determined by amide hydrogen exchange and mass spectrometry. Results of this
      study show that unfolding domains may include multiple, noncontiguous segments of
      the backbone and that different regions of helices may belong to different
      unfolding domains. In addition, these results show that the domain unfolding most
      rapidly is located distant from the subunit binding surfaces and has the greatest
      access to the denaturant. The bimodal intermolecular distributions of deuterium
      found in this study show that unfolding of these domains is cooperative. It is
      proposed that these unfolding domains are correlated with local energy minima in
      the free-energy folding surface of aldolase. In addition to the three unfolding
      domains, there are three short segments that do not unfold in 3 M urea. These
      segments, which are located in the subunit binding surface, identify the most
      stable regions of aldolase. This study also demonstrates that it is now possible
      to identify and characterize unfolding domains in relatively large (Mr 158 000)
      proteins.

PMID- 9572841
TI  - Structure of reduced DsbA from Escherichia coli in solution.
AB  - The three-dimensional structure of reduced DsbA from Escherichia coli in aqueous
      solution has been determined by nuclear magnetic resonance (NMR) spectroscopy and
      is compared with the crystal structure of oxidized DsbA [Guddat, L. W., Bardwell,
      J. C. A., Zander, T., and Martin, J. L. (1997) Protein Sci. 6, 1148-1156]. DsbA
      is a monomeric 21 kDa protein which consists of 189 residues and is required for
      disulfide bond formation in the periplasm of E. coli. On the basis of sequence
      specific 1H NMR assignments, 1664 nuclear Overhauser enhancement distance
      constraints, 118 hydrogen bond distance constraints, and 293 dihedral angle
      constraints were obtained as the input for the structure calculations by
      simulated annealing with the program X-PLOR. The enzyme is made up of two
      domains. The catalytic domain has a thioredoxin-like fold with a five-stranded
      beta-sheet and three alpha-helices, and the second domain consists of four alpha
      helices and is inserted into the thioredoxin motif. The active site between Cys30
      and Cys33 is located at the N terminus of the first alpha-helix in the
      thioredoxin-like domain. The solution structure of reduced DsbA is rather similar
      to the crystal structure of the oxidized enzyme but exhibits a different relative
      orientation of both domains. In addition, the conformations of the active site
      and a loop between strand beta5 and helix alpha7 are slightly different. These
      structural differences may reflect important functional requirements in the
      reaction cycle of DsbA as they appear to facilitate the release of oxidized
      polypeptides from reduced DsbA. The extremely low pKa value of the nucleophilic
      active site thiol of Cys30 in reduced DsbA is most likely caused by its
      interactions with the dipole of the active site helix and the side chain of
      His32, as no other charged residues are located next to the sulfur atom of Cys30
      in the solution structure.

PMID- 9572842
TI  - Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a
      transition-state inhibitor.
AB  - Nucleoside N-ribohydrolases are targets for disruption of purine salvage in the
      protozoan parasites. The structure of a trypanosomal N-ribohydrolase in complex
      with a transition-state inhibitor is reported at 2.3 A resolution. The
      nonspecific nucleoside hydrolase from Crithidia fasciculata cocrystallized with p
      aminophenyliminoribitol reveals tightly bound Ca2+ as a catalytic site ligand.
      The complex with the transition-state inhibitor is characterized by (1) large
      protein conformational changes to create a hydrophobic leaving group site (2) C3'
      exo geometry for the inhibitor, typical of a ribooxocarbenium ion (3)
      stabilization of the ribooxocarbenium analogue between the neighboring group 5'
      hydroxyl and bidentate hydrogen bonds to Asn168; and (4) octacoordinate Ca2+
      orients a catalytic site water and is liganded to two hydroxyls of the inhibitor.
      The mechanism is ribooxocarbenium stabilization with weak leaving group
      activation and is a departure from glucohydrolases which use paired carboxylates
      to achieve the transition state.

PMID- 9572843
TI  - Enzymes harboring unnatural amino acids: mechanistic and structural analysis of
      the enhanced catalytic activity of a glutathione transferase containing 5
      fluorotryptophan.
AB  - The catalytic characteristics and structure of the M1-1 isoenzyme of rat
      glutathione (GSH) transferase in which all four tryptophan residues in each
      monomer are replaced with 5-fluorotryptophan are described. The fluorine-for
      hydrogen substitution does not change the interaction of the enzyme with GSH even
      though two tryptophan residues (Trp7 and Trp45) are involved in direct hydrogen
      bonding interactions with the substrate. The rate constants for association and
      dissociation of the peptide, measured by stopped-flow spectrometry, remain
      unchanged by the unnatural amino acid. The 5-FTrp-substituted enzyme exhibits a
      kcat of 73 s-1 as compared to 18 s-1 for the native enzyme toward 1-chloro-2,4
      dinitrobenzene. That the increase in the turnover number is due to an enhanced
      rate of product release in the mutant is confirmed by the kinetics of the
      approach to equilibrium for binding of the product. The crystal structure of the
      5-FTrp-containing enzyme was solved at a resolution of 2.0 A by difference
      Fourier techniques. The structure reveals local conformational changes in the
      structural elements that define the approach to the active site which are
      attributed to steric interactions of the fluorine atoms associated with 5-FTrp146
      and 5-FTrp214 in domain II. These changes appear to result in the enhanced rate
      of product release. This structure represents the first of a protein substituted
      with 5-fluorotryptophan.

PMID- 9572844
TI  - The strongly conserved lysine 256 of Saccharomyces cerevisiae phosphoenolpyruvate
      carboxykinase is essential for phosphoryl transfer.
AB  - Lysine 256, a conserved amino acid of Saccharomycescerevisiae phosphoenolpyruvate
      (PEP) carboxykinase located in the consensus kinase 1a sequence of the enzyme,
      was changed to alanine, arginine, or glutamine by site-directed mutagenesis.
      These substitutions did not result in gross changes in the protein structure, as
      indicated by circular dichroism, tryptophan fluorescence spectroscopy, and gel
      exclusion chromatography. The three variant enzymes showed almost unaltered Km
      for MnADP but about a 20 000-fold decrease in Vmax for the PEP carboxylation
      reaction, as compared to wild-type PEP carboxykinase. The variant enzymes
      presented oxaloacetate decarboxylase activity at levels similar to those of the
      native protein; however, they lacked pyruvate kinase-like activity. The
      dissociation constant for the enzyme-MnATP complex was 1.3 +/- 0.3 microM for
      wild-type S. cerevisiae PEP carboxykinase, and the corresponding values for the
      Lys256Arg, Lys256Gln, and Lys256Ala mutants were 2.0 +/- 0.6 microM, 17 +/- 2
      microM, and 20 +/- 6 microM, respectively. These results collectively show that a
      positively charged residue is required for proper binding of MnATP and that
      Lys256 plays an essential role in transition state stabilization during
      phosphoryl transfer for S. cerevisiae PEP carboxykinase.

PMID- 9572845
TI  - Binding of the protein kinase PKR to RNAs with secondary structure defects: role
      of the tandem A-G mismatch and noncontiguous helixes.
AB  - The human interferon-induced double-stranded RNA (dsRNA)-activated protein kinase
      (PKR) is an antiviral agent that is activated by long stretches of dsRNA. PKR can
      also be activated or repressed by a series of cellular and viral RNAs containing
      non-Watson-Crick motifs. PKR has a dsRNA-binding domain (dsRBD) that contains two
      tandem copies of the dsRNA-binding motif (dsRBM). In vitro selection experiments
      were carried out to search for RNAs capable of binding to a truncated version of
      PKR containing the dsRBD. RNA ligands were selected by binding to His6-tagged
      proteins and chromatography on nickel(II) nitrilotriacetic acid agarose. A series
      of RNAs was selected that bind either similar to or tighter than a model dsRNA
      stem loop. Examination of these RNAs by a variety of methods, including sequence
      comparison, free-energy minimization, structure mapping, boundary experiments,
      site-directed mutagenesis, and footprinting, revealed protein-binding sites
      composed of noncontiguous helices. In addition, selected RNAs contained tandem A
      G mismatches (5'AG3'/3'GA5'), yet bound to the truncated protein with affinities
      similar to duplexes containing only Watson-Crick base pairs. The NMR structure of
      the tandem A-G mismatch in an RNA helix (rGGCAGGCC)2 reveals a global A-form
      helix with minor perturbations at the mismatch [Wu, M., SantaLucia, J., Jr., and
      Turner, D. H. (1997) Biochemistry 36, 4449-4460]. This supports the notion that
      dsRBM-containing proteins can bind to RNAs with secondary structure defects as
      long as the RNA has an overall A-form geometry. In addition, selected RNAs are
      able to activate or repress wild-type PKR autophosphorylation as well as its
      phosphorylation of protein synthesis initiation factor eIF-2, suggesting full
      length PKR can bind to and be regulated by RNAs containing a tandem A-G mismatch.

PMID- 9572846
TI  - Modulation of actin affinity and actomyosin adenosine triphosphatase by charge
      changes in the myosin motor domain.
AB  - The effects of mutations in an actin-binding surface loop of myosin (loop 2) are
      described. Part of loop 2, the segment between myosin residues 618 and 622, was
      replaced with sequences enlarged by the introduction of positively charged GKK or
      neutral GNN motifs. Constructs with loops carrying up to 20 additional amino
      acids and charge variations from -1 to +12 were produced. Steady-state and
      transient kinetics were used to characterize the enzymatic behavior of the mutant
      motor domains. Binding of nucleotide was not affected by any of the alterations
      in loop 2. In regard to their interaction with actin, constructs with moderate
      charge changes (-1 to +2) displayed wild-type-like behavior. Introduction of more
      than one GKK motif led to stronger coupling between the actin- and nucleotide
      binding sites of myosin and an up to 1000-fold increased affinity for actin in
      the absence of ATP and at zero ionic strength. In comparison to the wild-type
      construct M765, constructs with 4-12 extra charges displayed an increased
      dependence on ionic strength in their interaction with actin, a 2-3-fold increase
      in kcat, a more than 10-fold reduction in Kapp for actin, and a 34-70-fold
      increase in catalytic efficiency.

PMID- 9572847
TI  - Deletion of a highly motional residue affects formation of the Michaelis complex
      for Escherichia coli dihydrofolate reductase.
AB  - Analysis of the dihydrofolate reductase (DHFR) complex with folate by two
      dimensional heteronuclear (1H-15N) nuclear magnetic relaxation revealed that
      isolated residues exhibit diverse backbone fluctuations on the nanosecond to
      picosecond time scale [Epstein, D. M., Benkovic, S. J., and Wright, P. E. (1995)
      Biochemistry 34, 11037-11048]. These dynamical features may be significant in
      forming the Michaelis complex. Of these residues, glycine 121 displays large
      amplitude backbone motions on the nanosecond time scale. This amino acid,
      strictly conserved for prokaryotic DHFRs, is located at the center of the betaF
      betaG loop. To investigate the catalytic importance of this residue, we report
      the effects of Gly121 deletion and glycine insertion into the modified betaF
      betaG loop. Relative to wild type, deletion of Gly121 dramatically decreases the
      rate of hydride transfer 550-fold and the strength of cofactor binding 20-fold
      for NADPH and 7-fold for NADP+. Furthermore, DeltaG121 DHFR requires
      conformational changes dependent on the initial binary complex to attain the
      Michaelis complex poised for hydride transfer. Surprisingly, the insertion
      mutants displayed a significant decrease in both substrate and cofactor binding.
      The introduction of glycine into the modified betaF-betaG loop, however,
      generally eliminated conformational changes required by DeltaG121 DHFR to attain
      the Michaelis complex. Taken together, these results suggest that the catalytic
      role for the betaF-betaG loop includes formation of liganded complexes and proper
      orientation of substrate and cofactor. Through a transient interaction with the
      Met20 loop, alterations of the betaF-betaG loop can orchestrate proximal and
      distal effects on binding and catalysis that implicate a variety of enzyme
      conformations participating in the catalytic cycle.

PMID- 9572848
TI  - Strength of an interloop hydrogen bond determines the kinetic pathway in
      catalysis by Escherichia coli dihydrofolate reductase.
AB  - On the basis of X-ray crystallographic data, Sawaya and Kraut proposed that Met20
      loop conformational changes modulate ligand specificity observed in the catalytic
      cycle for Escherichia coli dihydrofolate reductase (DHFR) [Sawaya, M. R., and
      Kraut, J. (1997) Biochemistry 36, 586-603]. Interloop hydrogen bonds stabilize
      either a closed Met20 loop conformation observed in substrate complexes or an
      occluded Met20 loop conformation observed in product complexes, respectively. To
      test this model, we targeted a single hydrogen bond occurring exclusively in the
      closed Met20 loop conformation. Specifically, Asp122 in the betaF-betaG loop was
      independently substituted with asparagine, serine, and alanine-amino acids with
      decreasing abilities to hydrogen-bond. The kinetic analyses of the Asp122 mutants
      enabled the construction of kinetic schemes at pH 7.0 that demonstrate two
      striking features. First, a significant correlation exists between decreased
      binding of nicotinamide adenine dinucleotide phosphate, reduced (NADPH), and
      decreased hydride transfer rates resulting from these mutations. In other words,
      the interactions of Asp122 are along the reaction coordinate leading to the
      transition state. Second, substitutions for Asp122 alter the catalytic pathway
      preferred by wild-type DHFR under saturating conditions of substrate and
      cofactor. Overall, the steady-state rate contains contributions from the product
      off rates from the DHFR.5,6, 7,8-tetrahydrofolate (H4F) and DHFR.NADPH.H4F
      complexes and from the rate of hydride transfer. These mutational effects support
      the mechanistic model whereby interloop contacts regulate an equilibrium of Met20
      loop conformations that, in turn, modulate ligand affinity and turnover.

PMID- 9572849
TI  - Mapping of disulfide bridges in antifreeze proteins from overwintering larvae of
      the beetle Dendroides canadensis.
AB  - Antifreeze proteins (AFPs) have been identified in certain high-latitude marine
      fish, insects and other terrestrial arthropods, and plants. Despite considerable
      structural variation, the mechanisms of their noncolligative antifreeze activity
      are probably quite similar. AFPs hydrogen bond onto the surface of potential seed
      ice crystals at preferred growth sites, thereby preventing growth of the
      crystals. AFPs from overwintering larvae of the beetle Dendroidescanadensis are
      among the most active AFPs. These 8.7-kDa proteins consist of seven 12- or 13-mer
      repeating units. Their most striking feature is the location of cysteines every
      six residues throughout their length. Consequently, identification of the
      disulfide linkages of these cysteines is essential to understanding the structure
      of these AFPs. This study demonstrated that all of the 16 Cys residues in the
      Dendroides AFPs are disulfide bridged. All of the seven 12- or 13-mer repeats
      have internal disulfide bridges, and in all but the first repeat the Cys residues
      at positions 1 and 7 of the repeats are linked. In repeat 1 the Cys at position 1
      is linked to the Cys at position 10, rather than the Cys at position 7 as in the
      other repeats, and the Cys at position 7 of the first repeat is linked to a Cys
      at position 4 of the second repeat. The disulfide bridges probably function to
      position the hydrophilic side chains of serine and threonine residues so that
      they hydrogen bond with ice.

PMID- 9572850
TI  - Characterization of the ligand binding activities of vitronectin: interaction of
      vitronectin with lipids and identification of the binding domains for various
      ligands using recombinant domains.
AB  - Vitronectin is a multifunctional plasma glycoprotein which may regulate the
      systems related to protease cascades such as the coagulation, fibrinolysis, and
      complement systems as well as cell adhesion. Solid-phase assays and affinity
      chromatography on immobilized glycolipids indicated that vitronectin purified
      under denaturing conditions bound to sulfatide (Gal(3-SO4)beta1-1ceramide),
      cholesterol 3-sulfate, and various phospholipids, but not gangliosides. Only the
      unfolded or multimeric form of vitronectin bound to sulfatide, suggesting a
      conformational dependency of the binding activity, while vitronectin bound to
      cholesterol 3-sulfate regardless of its conformational state. The recombinant
      domains of human vitronectin and mutants with certain domains deleted were
      separately expressed in E. coli as fusion proteins. Using the recombinants,
      sulfatide-, phosphatidylserine-, cholesterol 3-sulfate-, Type I collagen-,
      heparin-, and beta-endorphin-binding activities were found to be attributable to
      hemopexin domain 2 and hemopexin domain 1. The possibility was suggested that the
      presence of a somatomedin domain and/or connecting region flanking hemopexin
      domain 1 inactivated its heparin binding. De-N-glycosylation of plasma
      vitronectin significantly affected the cholesterol sulfate- and collagen-binding
      activities, although its effects were opposite. These findings suggest that
      diverse ligand-binding activities could be attributed to pexin family motifs but
      that the interdomain interactions and glycosylations modulate the ligand binding
      activities of vitronectin.

PMID- 9572851
TI  - Palmitoylation of phospholipid scramblase is required for normal function in
      promoting Ca2+-activated transbilayer movement of membrane phospholipids.
AB  - Accelerated transbilayer movement of plasma membrane phospholipids (PL) plays a
      central role in the initiation of plasma clotting and in phagocytic clearance of
      injured or apoptotic cells. We recently identified a plasma membrane protein that
      induces rapid transbilayer movement of PL at elevated Ca2+, and we presented
      evidence that this PL scramblase mediates the transbilayer movement of plasma
      membrane PL in a variety of cells and tissues exposed to elevated intracellular
      Ca2+ [Zhou, Q. et al. (1997) J. Biol. Chem. 272, 18240-18244]. Activation of PL
      scramblase entails coordination of Ca2+ by a 12 residue segment resembling an EF
      hand loop motif that is adjacent to the single transmembrane helix of the
      polypeptide. On the assumption that correct orientation of the Ca2+-binding loop
      segment required a distal segment of the polypeptide to orient back toward the
      membrane, we considered the possibility of membrane anchoring through covalent
      fatty acid. Human Raji cells transformed with PL scramblase cDNA in the
      expression vector pEGFP-C2 were metabolically labeled with [3H]palmitate, and
      fusion protein immunoprecipitated with antibody against GFP-PL scramblase was
      found to covalently incorporate 3H, whereas no radioactivity was covalently
      associated with GFP. The identity of the covalently bound 3H in PL scramblase as
      a thioester-linked [3H]palmitate was confirmed by hydroxylamine cleavage and by
      thin-layer chromatography of the liberated fatty acid. Consistent with the
      assumption that activation by Ca2+ might require accessory site(s) of polypeptide
      attachment to the membrane, hydrolysis of thioester bonds in purified erythrocyte
      PL scramblase markedly reduced the Ca2+-dependent activity of the membrane
      incorporated protein.

PMID- 9572852
TI  - Formation of nitric oxide synthase-iron(II) nitrosoalkane complexes: severe
      restriction of access to the iron(II) site in the presence of
      tetrahydrobiopterin.
AB  - Nitric oxide synthases (NOS) are heme proteins, closely related to cytochromes
      P450, that catalyze oxidation of l-arginine (l-Arg) to nitric oxide (NO) and
      citrulline. To get further insight into their active site, we have studied the
      ability of recombinant mouse inducible NOS (iNOS) and rat brain neuronal NOS
      (nNOS), and of their oxygenase domains (iNOSoxy and nNOSoxy), to form Fe(II)
      nitrosoalkane complexes. In the absence of BH4, iNOSoxy, nNOSoxy, and full-length
      iNOS readily form complexes characterized by Soret peaks around 448 nm, after
      reaction with various nitroalkanes and sodium dithionite. These complexes
      displayed physicochemical characteristics very similar to those of previously
      reported microsomal cytochrome P450-Fe(II)-nitrosoalkane complexes: (i) a Soret
      peak around 450 nm, (ii) a clear stability in the presence of CO, and (iii) a
      fast destruction upon oxidation of the iron by ferricyanide. Thus, in the absence
      of l-Arg and BH4, NOSs Fe(II) appear to be largely opened to even large R-NO
      ligands with R = cyclohexyl or p-Cl-C6H4-CH2CH(CH3) for instance, in a manner
      similar to microsomal P450s Fe(II). As expected, the presence of l-Arg inhibits
      the formation of NOSs Fe(II)-RNO complexes. More surprisingly, the presence of
      BH4 also strongly inhibits the formation of the NOSs Fe(II) complexes even with
      the smallest nitrosoalkane ligand, CH3NO (IC50 values of 0.5 and 4 microM for
      nNOSoxy and iNOSoxy, respectively). Accordingly, recombinant full-length nNOS
      containing BH4 and l-Arg is completely unable to form Fe(II)-nitrosoalkane
      complexes, even with CH3NO. These results suggest that, in the absence of l-Arg
      and BH4, the distal pocket of NOSs Fe(II) is largely opened even to bulky
      ligands, in a manner similar to that of microsomal cytochromes P450. On the
      contrary, the distal heme pocket of iNOS and nNOS seems to be closed after
      binding of l-Arg and BH4, particularly in the Fe(II) state. This results in a
      highly restricted access for Fe(II) ligands, except very small ones such as CO,
      NO, and O2. Such effects of BH4 in controlling the size of the distal heme pocket
      of NOS Fe(II) correspond to a new role of biopterins in biological systems.

PMID- 9572853
TI  - An ester bond linking a fragment of a serine proteinase to its serpin inhibitor.
AB  - Most known members of the serpin superfamily are serine proteinase inhibitors.
      Serpins are therefore important regulators of blood coagulation, complement
      activation, fibrinolysis, and turnover of extracellular matrix. Serpins form SDS
      resistant complexes of 1:1 stoichiometry with their target proteinases by
      reaction of their P1-P1' peptide bond with the active site of the proteinases.
      The nature of the interactions responsible for the high stability of the
      complexes is a controversial issue. We subjected the complex between the serine
      proteinase urokinase-type plasminogen activator (uPA) and the serpin plasminogen
      activator inhibitor-1 (PAI-1) to proteolytic digestion under nondenaturing
      conditions. The complex could be degraded to a fragment containing two disulfide
      linked peptides from uPA, one of which included the active site Ser, while PAI-1
      was left undegraded. By further proteolytic digestion after denaturation and
      reduction, it was also possible to degrade the PAI-1 moiety, and we isolated a
      fragment containing 10 amino acids from uPA, encompassing the active site Ser,
      and 6 amino acids from PAI-1, including the P1 Arg. Characterization of the
      fragment gave results fully in agreement with the hypothesis that it contained an
      ester bond between the hydroxyl group of the active site Ser and the carboxyl
      group of the P1 Arg. These data for the first time provide direct evidence that
      serine proteinases are entrapped at an acyl intermediate stage in serine
      proteinase-serpin complexes.

PMID- 9572854
TI  - Arginine 719 in human plasminogen mediates formation of the
      staphylokinase:plasmin activator complex.
AB  - Staphylokinase (Sak), a 16-kDa bacterial protein, forms a 1:1 stoichiometric
      complex with the serine proteinase domain of human plasmin, which in turn
      converts other plasminogen molecules into plasmin. To identify amino acid
      residues critical for generating the Sak:plasmin activator complex, alanine
      scanning mutagenesis was performed on phage-displayed micro-plasminogen
      (microPlg). Substitution of Arg719 with Ala [microPlg(R719A)] disrupted complex
      formation, although the sensitivity of phage-displayed microPlg(R719A) to
      activation by urokinase and the amidolytic activity of the micro-plasmin
      derivative [microPli(R719A)] remained unaffected. Likewise, the soluble
      microPlg(R719A) molecule did not generate a functional activator complex with
      Sak, whereas quantitative activation into plasmin was obtained upon incubation
      with either urokinase or the Sak:plasmin complex. Real-time biospecific affinity
      measurements revealed that the Arg --> Ala substitution at position 719 increased
      the equilibrium dissociation constant between microPlg(R719A) and Sak from 46 nM
      to 1 microM, primarily by reducing the association rate constant. Arg719 has
      recently also been implied in the functional complex formation between human
      plasmin and streptokinase [Dawson, K. M., Marshall, J. M., Raper, R. H., Gilbert,
      R. J., and Ponting, C. P. (1994) Biochemistry 33, 12042-12047.], suggesting that
      both bacterial cofactors may share common structural and/or mechanistic aspects
      for plasminogen activation.

PMID- 9572855
TI  - Reversible denaturation, self-aggregation, and membrane activity of Escherichia
      coli alpha-hemolysin, a protein stable in 6 M urea.
AB  - Escherichia coli alpha-hemolysin (HlyA) is an extracellular protein toxin (107
      kDa) whose cell lytic activity may be preserved for months at -20 degreesC in the
      presence of 6 M urea, although it decays rapidly in urea-free buffers. This paper
      describes experiments addressed to unravel the role of urea in HlyA
      stabilization. Urea up to 8 M inhibits the Ca2+-binding and hemolytic activities
      of the protein, alters its secondary and tertiary structures, and reduces its
      tendency to self-aggregation. All these changes are largely reversed upon urea
      removal by dilution or dialysis, suggesting that they are interrelated.
      Furthermore, the extent of recovery of the native activities and structural
      features of alpha-hemolysin that follows urea removal increases with the
      concentration of urea during the previous phase. Thus, it seems that urea elicits
      the reversible transition of HlyA to a less active but more stable state whose
      structure differs significantly from that of the native protein. Moreover
      dialysis equilibration of the protein with buffers containing 3 M urea induces
      the formation of a molecular form of HlyA 5-10 times more active than the native
      protein in the absence of urea. This hyperactive intermediate appears to keep the
      native secondary structure of HlyA, but with a less compact tertiary structure,
      that increases the number of exchangeable Ca2+ ions under these conditions.
      Changes in the intrinsic fluorescence of HlyA also support the notion of a
      conformational change in the high-activity intermediate. The intermediate is only
      detected when assayed in the presence of Ca2+ and 3 M urea and can bind a large
      number of calcium ions (approximately 12 vs approximately 3 for the native
      protein); it shows a large tendency to self-aggregation and presumably, in the
      presence of membranes, a similar tendency to irreversible insertion, which may be
      the reason for its high lytic activity.

PMID- 9572856
TI  - Resonance raman characterization of reaction centers with an Asp residue near the
      photoactive bacteriopheophytin.
AB  - Qy-excitation resonance Raman (RR) studies are reported for a series of
      Rhodobacter capsulatus reaction centers (RCs) containing mutations at L
      polypeptide residue 121 near the photoactive bacteriopheophytin (BPhL). The
      studies focus on the electronic/structural perturbations of BPhL induced by
      replacing the native Phe with an Asp residue. Earlier work has shown that the
      electron-transfer properties of F(L121)D RCs are closely related to those of RCs
      in which BPhL is replaced by bacteriochlorophyll (BChl) (beta-type RCs) or by
      pheophytin. In addition to the F(L121)D single mutant, RR studies were performed
      on the F(L121)D/E(L104)L double mutant, which additionally removes the hydrogen
      bond between BPhL and the native Glu L104 residue. The vibrational signatures of
      BPhL in the single and double mutants containing Asp L121 are compared with one
      another and with those of BPhL in both wild-type and F(L121)L RCs. The
      replacement of the aromatic Phe residue with Leu has no discernible effect on the
      vibrational properties of BPhL, a finding in concert with the previously reported
      absence of an effect of the mutation on the electron-transfer characteristics of
      the RC. In contrast, replacement of Phe with Asp significantly perturbs the
      vibrational characteristics of BPhL, and in a manner most consistent with Asp
      L121 being deprotonated and negatively charged. The negative charge of the
      carboxyl group of Asp L121 interacts with the pi-electron system of BPhL in a
      relatively nonspecific fashion, diminishing the contribution of charge-separated
      resonance forms of the C9-keto group to the electronic structure of the cofactor.
      The presence of a negative charge near BPhL is consistent with the known
      photochemistry of F(L121)D RCs, which indicates that the free energy of P+BPhL-
      is substantially higher than in wild-type RCs.

PMID- 9572857
TI  - Multiple conformations of physiological membrane-bound cytochrome c.
AB  - One-tenth of cytochrome c (cyt c) remains bound to the inner mitochondrial
      membrane (IMM) at physiological ionic strength (I; i.e. , I approximately 150
      mM), exhibiting decreased electron transport (ET) activity. We now show that this
      form of membrane-bound cyt c (MB-cyt c) can be obtained in vitro and that binding
      to membranes at low I generates an additional conformation with higher ET
      activity. This low I bound form of MB-cyt c (MBL-cyt c) exhibited intrinsic ET
      rates similar to those of electrostatically bound cyt c (EB-cyt c). The ET
      activity of IMM-bound MB-cyt c approached slowly that of MBL-cyt c or EB-cyt c,
      suggesting that MB-cyt c converts to MBL-cyt c while bound to IMM. When
      maintained at physiological I, both forms of MB-cyt c were released from the
      membrane, indicating that they convert to an EB-cyt c-like form. This process may
      be very dynamic in cellular mitochondria, as binding and release for both MB-cyt
      c forms increased considerably with temperature. I-Dependent binding of MB-cyt c
      does not require IMM, and it can be reproduced using large or small unilamellar
      vesicles (SUV). Using SUV-cyt c complexes, we characterized the secondary
      structure of MB-cyt c and MBL-cyt c by circular dichroism. Conformational
      analysis revealed that cyt c binding as MB-cyt c decreases its alpha-helical
      content (70-79%) and increases its beta-sheet up to 135%. The secondary structure
      of MBL-cyt c was similar to that of EB-cyt c and soluble cyt c, with a modest
      increase in beta-sheet. Taken together, our experiments suggest that
      physiological cyt c exists in soluble and membrane-bound conformations with
      similar ET activity, which may exchange very rapidly, and that soluble
      hydrophilic proteins can bind transiently to biomembranes.

PMID- 9572858
TI  - Acidic pH promotes dimerization of Bcl-2 family proteins.
AB  - Several members of the apoptosis-regulating Bcl-2 family of proteins can homo- or
      heterodimerize with each other at neutral pH and can also form ion channels in
      synthetic membranes at low pH. The effects of low pH on dimerization among these
      proteins, however, have not heretofore been examined. Surface plasmon resonance
      was used to examine the kinetics of dimerization as a function of pH between the
      anti-apoptotic protein Bcl-XL (applied in the mobile phase) and three other
      members of the Bcl-2 family: Bcl-2, Bax, and Bid (immobilized on biosensor
      chips). In all cases, the relative affinity of dimerization was substantially
      increased at pH 4.0 compared to pH 7.0-7.4, ranging from a approximately 10-fold
      enhancement for Bcl-XL/Bcl-XL homodimers to >60-fold for Bcl-XL/Bid heterodimers.
      Comparison of the apparent association (ka) and dissociation (kd) rates at
      neutral and acidic pH revealed that the major contributor to increased affinity
      at low pH was a decreased rate of dimer dissociation. Thus, low pH stabilizes
      homo- and heterodimeric complexes comprised of Bcl-XL and these other Bcl-2
      family proteins. At pH 4.0, the circular dichroism spectra of Bcl-XL and Bax were
      essentially unchanged relative to pH 7.0-7.4, indicating a complete retention of
      alpha-helical secondary structure at low pH and excluding gross denaturation of
      the proteins. Size-exclusion chromatography and bisANS (4,4'-dianilino-1, 1'
      binaphthyl-5,5'-disulfonic acid) labeling studies provided indirect evidence that
      Bcl-XL may undergo conformational changes at low pH. The findings are discussed
      with respect to the mechanisms of ion-channel formation by Bcl-2 family proteins
      and the putative molten globule state that has been proposed for these and
      structurally similar proteins.

PMID- 9572859
TI  - Detection of a new substrate-derived radical during inactivation of
      ribonucleotide reductase from Escherichia coli by gemcitabine 5'-diphosphate.
AB  - Ribonucleotide reductases (RNRs) play a central role in replication and repair by
      catalyzing the conversion of nucleotides to deoxynucleotides. Gemcitabine 5'
      diphosphate (F2CDP), the nucleoside of which was recently approved by the FDA for
      treatment of pancreatic cancer, is a potent mechanism-based inhibitor of class I
      and II RNRs. Inactivation of the Eschericia coli class I RNR is accompanied by
      loss of two fluorides and one cytosine. This RNR is composed of two homodimeric
      subunits: R1 and R2. R1 is the site of nucleotide reduction, and R2 contains the
      essential diferric-tyrosyl radical cofactor. The mechanism of inactivation
      depends on the availability of reductant. In the presence of reductant
      [thioredoxin (TR)/thioredoxin reductase (TRR)/NADPH or dithiothreitol],
      inhibition results from R1 inactivation. In the absence of reductant with
      prereduced R1 and R2, inhibition results from loss of the essential tyrosyl
      radical in R2. The same result is obtained with C754S/C759S-R1 in the presence of
      TR/TRR/NADPH. In both cases, tyrosyl radical loss is accompanied by formation of
      a new stable radical (0.15-0.25 equiv/RNR). EPR studies in 2H2O, with [U-2H]R1,
      and examination of the microwave power saturation of the observed signal,
      indicate by process of elimination that this new radical is nucleotide-based. In
      contrast to all previously investigated 2'-substituted nucleotide inhibitors of
      RNR, inactivation is not accompanied by formation of a new protein-associated
      chromophore under any conditions. The requirement for reductant in the R1
      inactivation pathway, the lack of chromophore on the protein, the loss of two
      fluoride ions, and the stoichiometry of the inactivation all suggest a unique
      mechanism of RNR inactivation not previously observed with other 2'-substituted
      nucleotide inhibitors of RNR. This unique mode of inactivation is proposed to be
      responsible for its observed clinical efficacy.

PMID- 9572860
TI  - Kinetic and spectroscopic properties of the YZ* radical in Ca2+- and Cl--depleted
      photosystem II preparations.
AB  - Depletion of Ca2+ and/or Cl- ions from PSII membranes blocks the electron
      transfer reactions that precede O2 evolution on the oxidizing side of the enzyme.
      Illumination of these inhibited preparations at 273 K generates a paramagnetic
      species that is detectable by low-temperature (T < 20 K) EPR as a signal in the g
      = 2 region, 90-230 G wide, depending on the treatment that PSII has undergone.
      This signal has recently been assigned to YZ* in magnetic interaction with the
      manganese cluster in its S2 state [Gilchrist et al. (1995) Proc. Natl. Acad. Sci.
      U.S.A. 92, 9545-9549]. This view, however, is not universal, owing, in part, to
      the fact that its spectroscopic properties depend on the preparation and the
      experimental conditions used for its study and, in part, to uncertainties as to
      the room temperature behavior of YZ* in inhibited preparations. Here, we report
      time-resolved and conventional EPR data showing that, at room temperature and at
      273 K, YZ* can be accumulated in its 20 G form in high yields in both Ca2+
      depleted and acetate-inhibited preparations, and that the kinetics of its decay
      match the decay kinetics of the low-temperature signal generated in corresponding
      samples. The properties of the YZ* signal, however, are shown to depend on the
      polypeptide content, the temperature, and the electron donors and acceptors
      present in the sample under examination. Our results support assignment of the
      EPR signal in inhibited preparations to S2 YZ* and demonstrate a protective role
      of the 17 and 23 kDa extrinsic polypeptides for the manganese cluster against
      externally added reductants.

PMID- 9572861
TI  - Characterization of the ubiquinone reduction site of mitochondrial complex I
      using bulky synthetic ubiquinones.
AB  - A wide variety of alkyl derivatives of Q2 (6-geranyl-2, 3-dimethoxy-5-methyl-1,4
      benzoquinone) and DB (6-n-decyl-2, 3-dimethoxy-5-methyl-1,4-benzoquinone), in
      which methoxy groups of the 2- and/or 3-positions of the quinone ring were
      replaced by other bulky alkoxy groups from ethoxy to butoxy, were prepared by
      novel synthetic procedures. Electron-accepting activities of the bulky quinones
      were investigated with bovine heart mitochondrial complex I and its counterpart
      of Paracoccus denitrificans(NDH-1) to elucidate structural and functional
      features of the quinone reduction site of the enzymes. The bulky quinone
      analogues served as sufficient electron acceptors from the physiological quinone
      reduction site of bovine complex I. Considering the very poor activities of even
      the ethoxy derivatives as substrates for other respiratory enzymes such as
      mitochondrial complexes II and III [He, D. Y., Gu, L. Q., Yu, L., and Yu, C. A.
      (1994) Biochemistry 33, 880-884], this result indicated that the quinone
      reduction site of bovine complex I is spacious enough to accommodate bulky
      exogenous substrates. In contrast to bovine complex I, bulky quinone analogues
      served as poor electron acceptors with Paracoccus NDH-1. These observations
      indicated that bovine complex I recognizes the substrate structure with poor
      specificity. The substituent effects in the 2- and 3-positions of the quinone
      ring on the electron-transfer activity with bovine complex I differed
      significantly between Q2 and DB series despite having the same total number of
      carbon atoms in the side chain. The inhibitory effect involving Q2 due to its
      geranyl side chain was markedly diminished by structural modifications of the
      quinone ring moiety. These findings indicate that the side chain plays a specific
      role in the redox reaction and that the quinone ring and side-chain moieties
      contribute interdependently to binding interaction. Moreover, structural
      dependency of the proton-pumping activity of the quinone analogues was comparable
      to that of the electron-transfer activity with bovine complex I, indicating that
      the mechanism of redox-driven proton-pumping does not differ depending upon the
      substrate structure.

PMID- 9572862
TI  - Single-chain lambda Cro repressors confirm high intrinsic dimer-DNA affinity.
AB  - The overall affinity of the bacteriophage lambda Cro repressor for its operator
      DNA site is limited by dimer dissociation at submicromolar concentrations. Since
      Cro dimer-operator complexes form at nanomolar concentrations of Cro subunits
      where free dimers are rare, these dimers must bind with compensating high
      affinities. Previous studies of the covalent dimer Cro V55C suggest little change
      in DNA binding affinity even though the dimeric species is quantitatively
      populated; this is an apparent contradiction to the expectation of high intrinsic
      dimer-DNA affinity. In contrast to the disulfide linkage at the center of the
      dimer interface in Cro V55C, polypeptide linkers that join the two subunits allow
      single-chain Cro repressors to bind operator DNA with picomolar affinities. A
      series of five single-chain Cro repressors have been expressed from fused tandem
      cro genes. Each contains a peptide linker of 8-16 hydrophilic residues that
      connects the C-terminus of one subunit to the N-terminus of the next. All bind to
      operator DNA with at least 100-fold higher affinity than Cro V55C. Proteins
      containing the longest and shortest linkers have been purified and characterized
      in detail. Both exhibit similar CD spectra to wild-type Cro and enhanced thermal
      stability. Sedimentation equilibrium experiments show that single-chain Cro
      repressors do not associate at concentrations up to 30 microM. The rate of
      dissociation of Cro-DNA complexes is almost unchanged by covalent linkage.
      Biophysical characterization of Cro variants such as these, where DNA binding is
      uncoupled from subunit assembly, is necessary for a quantitative understanding of
      the structural and energetic determinants of DNA recognition in this simple model
      system.

PMID- 9572863
TI  - Catalytic center of DNA polymerase beta for excision of deoxyribose phosphate
      groups.
AB  - The amino-terminal 8-kDa domain of vertebrate DNA polymerase beta (pol beta) has
      an activity to excise deoxyribose phosphate (dRP) groups from 5'-incised
      apurinic/apyrimidinic (AP) sites during base excision repair. The excision
      reaction proceeds via a beta-elimination reaction following formation of a Schiff
      base between an aldehyde group of the AP site and an amino group of the enzyme.
      Here we report that the Lys-72 residue of this enzyme is the catalytic center for
      dRP excision. Substitutions of Lys-72 with Arg or Gln reduced the dRP excision
      activity to less than 1% of the wild-type 8-kDa domain, while substitutions of
      Lys-35, Lys-68, or Lys-84 did not abolish its activity. The Lys-72 mutations also
      significantly decreased Schiff base intermediates trapped by reduction with
      sodium borohydride. The 8-kDa domain alone was able to bind preferentially to a
      single-nucleotide gap or 5'-incised synthetic AP site on double-stranded DNA. The
      Lys-72 mutations did not affect this damage-specific DNA binding activity. When
      introduced into the intact enzyme, a mutation of Lys-72 to Arg did not affect DNA
      synthesis activity of pol beta, but eliminated the repair activity. Addition of
      the wild-type 8-kDa domain to this reaction restored the repair activity. These
      results indicate a specific role of Lys-72 of pol beta in the dRP excision during
      base excision repair.

PMID- 9572864
TI  - A substrate recognition role for the [4Fe-4S]2+ cluster of the DNA repair
      glycosylase MutY.
AB  - The Escherichia coli DNA repair enzyme MutY plays an important role in the
      recognition and repair of 7, 8-dihydro-8-oxo-2'-deoxyguanosine: 2'-deoxyadenosine
      (OG:A) mismatches in DNA [Michaels et al. (1992) Proc. Natl. Acad. Sci. U.S. A.
      89, 7022-7025]. MutY prevents mutations due to misincorporation of A opposite OG
      during DNA replication by removing the adenine base. This enzyme has significant
      sequence homology with the [4Fe-4S]2+ cluster-containing DNA repair enzyme,
      endonuclease III [Michaels et al. (1990) Nucleic AcidsRes. 18, 3841-3845]. In the
      present study, we have investigated the importance of cluster assembly in folding
      of MutY. MutY was denatured and then refolded in the presence or absence of
      ferrous and sulfide ions. Denatured MutY can refold in the presence of ferrous
      and sulfide ions to provide active enzyme. This suggests the cluster can self
      assemble and that this process is facile in vitro. Interestingly, CD spectra and
      Tm measurements of MutY refolded with and without ferrous and sulfide ions are
      essentially identical, implying that assembly of the cluster is not required for
      MutY folding. Additionally, Tm measurements indicated that the [4Fe-4S]2+ cluster
      does not contribute significantly to the overall thermal stability of MutY.
      Refolded forms of MutY which lack the cluster are unable to perform the adenine
      glycosylase function and bind to DNA. However, these inactive folded forms regain
      activity by addition of ferrous and sulfide ions. This indicates that the Fe-S
      cluster may have a superficial location, allowing for its assembly after folding.
      More importantly, these results provide evidence that the presence of the [4Fe
      4S]2+ cluster is critical for the specific recognition of substrate DNA necessary
      for the adenine glycosylase activity of MutY.

PMID- 9572865
TI  - Spermine switches a Neurospora VS ribozyme from slow Cis cleavage to fast trans
      cleavage.
AB  - In keeping with the known role of polyamines as counterions in RNA folding, we
      have found that concentrations of spermine as low as 1 microM facilitate first
      order Cis cleavage and decrease the concentration of magnesium required for
      optimal cleavage of the VS ribozyme. Surprisingly, under certain experimental
      conditions, cleavage reactions at concentrations of spermine above about 20
      microM were not first-order. At 100 microM spermine, about half of the RNA
      cleaved in an initial very fast burst, k >/= 5 min-1, about 100-fold faster than
      under our previously optimized conditions; the remainder of the RNA cleaved more
      slowly. The extent of the burst and the initial rate of cleavage were
      proportional to RNA concentration, suggesting that the fast phase was due to
      intermolecular trans cleavage involving two or more RNAs. This inference of trans
      cleavage was confirmed by demonstrating spermine-dependent trans cleavage of
      particular combinations of mutant RNAs that were each incapable of cis cleavage.
      The experimental conditions required to switch the VS ribozyme into trans
      cleavage mode are quite stringent. The RNA must be preincubated with an adequate
      concentration of spermine at very low ionic strength near neutral pH.
      Concentrations of buffers and salts typically used in in vitro studies of
      ribozymes, including those used in our previous characterization of the VS
      ribozyme, are sufficiently high that they prevent or reverse the trans cleaving
      RNA conformation. The ability to switch cleavage modes from cis to trans provides
      an experimental system to study different active conformations of VS RNA, as well
      as to investigate the functional consequences of polyamine-RNA interactions.

PMID- 9572866
TI  - DNA structural integrity and base composition affect ultraviolet light-induced
      oxidative DNA damage.
AB  - We previously demonstrated that ultraviolet (UV) light (254 nm) induced the
      formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA via a singlet oxygen
      mechanism. In the present paper, we provide novel findings that DNA structure and
      base composition significantly affect the yield of 8-OHdG by UV radiation. Unlike
      ionizing radiation that induces 8-OHdG both in free 2'-deoxyguanosine (dG) and in
      DNA, UV light induced 8-OHdG formation in intact DNA and polydG.dC, but not in
      dG. When thermally denatured DNA was irradiated with UV light, the yield of 8
      OHdG was reduced by more than 80% compared to intact DNA. Oxygenation of the
      denatured DNA solution did not restore the yield of UV-induced 8-OHdG.
      Irradiation of DNA with different AT/GC ratios showed that the yield of UV
      induced 8-OHdG varied in proportion to the AT content, suggesting that AT base
      pairs in DNA enhance generation of the oxidizing species and subsequent oxidation
      of dG. The natural antioxidants genistein, estradiol, protocatechuic acid (PCA),
      and oleanolic acid (OA) were investigated for their inhibition of UV-induced 8
      OHdG. Genistein and estradiol, that intercalate into DNA as shown by a computer
      modeling, significantly quenched UV-induced 8-OHdG, whereas PCA and OA did not
      fit into DNA and exhibited weak or no effect. These results suggest that the
      intercalation of genistein and estradiol into DNA may alter the DNA structural
      integrity, interrupt the production of oxidizing species, and subsequently reduce
      the formation of 8-OHdG by UV radiation.

PMID- 9572867
TI  - Oxidative charge transfer To repair thymine dimers and damage guanine bases in
      DNA assemblies containing tethered metallointercalators.
AB  - Potent oxidants which intercalate in DNA serve as tools to probe DNA-mediated
      electron-transfer reactions. A photoexcited rhodium intercalator, Rh(phi)2DMB3+
      (phi = 9,10-phenanthrenequinone diimine and DMB = 4,4'-dimethyl-2,2'-bipyridine),
      tethered to DNA, promotes both oxidative damage to 5'-GG-3' doublets in DNA and
      the repair of thymine dimers from a remote site on the DNA duplex. DNA-mediated
      repair of a thymine dimer lesion by charge transfer from the tethered rhodium
      intercalator is quantitative, albeit with low photoefficiency, occurs in an
      intraduplex reaction over long range (36 A), and requires that the intervening
      bases be paired. When both oxidative reactions, repair and oxidative damage, are
      monitored on the same duplex, competition is evident; the presence of both a 5'
      GG-3' site and the thymine dimer diminished the dimer repair efficiency by 20-40%
      and decreased damage at the 5'-GG-3' sites 2-fold compared to similar sequences
      lacking either the guanine doublet or thymine dimer, respectively. In addition to
      damage at the 5'-G of 5'-GG-3' sites, we also observe oxidation at the 3'-G of
      the 5'-GT<>TG-3' tetrad only in the presence of thymine dimer. Overall, the yield
      of repaired thymine strand was at least 10 times higher than the yield of
      oxidized guanine in the same sequences. While the 5-GG-3' may represent the
      thermodynamically favored site for oxidative reaction, repair of the thymine
      dimer appears to be kinetically more favorable. Dipyridophenanzine (dppz)
      complexes of ruthenium(III), less potent oxidants which intercalate in DNA,
      oxidize 5'-GG-3' doublets efficiently but cannot trigger the repair of the
      thymine dimer lesion. Oxidative damage to DNA from a distance, mediated by the
      DNA base pair stack, can, however, be utilized to probe the disruption in the
      base stack generated by the thymine dimer. The presence of the dimer does not
      diminish oxidation by a Ru(III) intercalator at a distal guanine doublet,
      suggesting that the disruption caused by the dimer does not block charge transfer
      through the DNA duplex. DNA-mediated electron-transfer reactions of
      metallointercalators therefore serve to illustrate important aspects of radical
      migration and its consequence with respect to reactions at a distance through the
      DNA base pair stack.

PMID- 9572868
TI  - Proximity of the nucleotide binding domains of the P-glycoprotein multidrug
      transporter to the membrane surface: a resonance energy transfer study.
AB  - Very little structural information is available for P-glycoprotein (Pgp), which
      has been implicated in the multidrug resistance of human tumors because of its
      ability to act as an ATP-driven efflux pump for hydrophobic compounds. Highly
      purified Pgp has been labeled on two cysteine residues with the fluorescence
      probe NBD-Cl (7-chloro-4-nitro-2,1,3-benzoxadiazole). We show that NBD labels the
      same cysteine residues as MIANS [2-(4-maleimidoanilino)naphthalene-6-sulfonic
      acid]; they are located within the Walker A motif of the nucleotide binding
      domain, close to the site where ATP binds. NBD- and MIANS-labeled Pgps were
      reconstituted by detergent dilution into phospholipid vesicles containing
      increasing mole fractions of rhodamine- or NBD-labeled phosphatidylethanolamine
      (PE), respectively. The fluorescence of the NBD-Pgp and MIANS-Pgp donors was
      quenched in a concentration-dependent manner by the rhodamine-PE and NBD-PE
      acceptors. Using two different methods to analyze Forster resonance energy
      transfer, the distance of the Pgp-bound probes from the lipid-water interfacial
      region of the bilayer was estimated to be 31-35 A. This distance is compatible
      with the low-resolution structure of Pgp determined by electron microscopy, and
      indicates that the nucleotide binding domains lie close to the membrane surface.
      The experimental data fitted very well to theoretical quench curves for a single
      protein-bound fluor, suggesting that the two nucleotide binding domains are
      located equidistant from the bilayer. Following the addition of ATP to MIANS-Pgp,
      the NBD-PE quench curve no longer conformed to the models. These results imply
      that Pgp interacts differently with PE when it is in the ATP-bound form.

PMID- 9572869
TI  - Phosphatidylcholine activation of bacterial phosphatidylinositol-specific
      phospholipase C toward PI vesicles.
AB  - The effect of different phospholipids on the kinetic behavior of
      phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus
      thuringiensis toward PI vesicles has been investigated. Cosonicated PC/PI
      vesicles displayed enhanced hydrolysis of PI when less than 0. 20 mole fraction
      PC was incorporated into the vesicle; higher mole fractions of PC led to a
      decrease from the maximum activity mimicking surface dilution of substrate. Since
      the PC could affect PI-PLC binding to vesicles, the effect of separate PC
      vesicles on enzymatic hydrolysis of PI vesicles was examined. Separate
      phosphatidylcholine vesicles were found to activate PI-PLC-catalyzed cleavage of
      PI vesicles up to 7-fold. The activation was completely abolished when the PC
      vesicle was composed of cross-linked molecules. In the absence of enzyme,
      fluorescence resonance energy transfer studies did not detect any fusion between
      PI and PC vesicles if the total lipid concentration was below 2 mM. Higher total
      lipid concentrations (>20 mM) increased PC transfer between PC and PI vesicles,
      producing a PI vesicle population with small amounts of PC in the outer
      monolayer. This suggested that the activation of PI-PLC toward PI vesicles
      reflects the time scale of transfer of PC from PC vesicles to PI vesicles.
      Cosonicated PC/PI vesicles provide a measure of enzyme activity versus mole
      fraction of PC that can be used to estimate the extent of vesicle exchange or
      fusion between separate vesicle pools. The effects of other phospholipid vesicles
      on PI-PLC hydrolysis of PI were also examined; zwitterionic lipids were
      activators while anionic phospholipids inhibited activity. The results indicated
      that PC molecules in the PI interface allosterically bind to PI-PLC and help
      anchor enzyme in a more active conformation to the PI interface.

PMID- 9572870
TI  - Phosphorylation of calmodulin alters its potency as an activator of target
      enzymes.
AB  - Previous work has shown that calmodulin (CaM) is constitutively phosphorylated in
      rat liver, probably by casein kinase II [Quadroni, M., James, P., and Carafoli,
      E. (1994) J. Biol. Chem. 269, 16116-16122]. A procedure is now described for the
      isolation of the phosphorylated forms of calmodulin (PCaM) free from CaM, since
      in vitro phosphorylation experiments yield a 50:50 mixture of 3-4 times
      phosphorylated CaM and native CaM. The activation of six target enzymes by PCaM
      was tested: myosin light chain kinase, 3',5'-cyclic nucleotide phosphodiesterase,
      plasma membrane Ca2+-ATPase, Ca2+-CaM-dependent protein phosphatase 2B
      (calcineurin), neuronal nitric oxide synthase, and CaM-kinase II. In general, the
      phosphorylation of CaM caused a decrease in enzyme binding affinity, increasing
      the Kact by 2-4-fold for MLCK, PDE, PM Ca2+-ATPase, and calcineurin. The Vmax at
      saturating concentrations of PCaM was less affected, with the exception of CaM
      kinase II, which was only minimally activated by PCaM and NOS whose Vmax was
      increased 2.6 times by PCaM with respect to CaM. Phosphorylation of calmodulin
      had very little effect on the binding of calcium to the enzyme despite the fact
      that Ser 101 which is phosphorylated is located in the third calcium binding
      loop. CD measurements performed on CaM and PCaM indicated that phosphorylation
      causes a marked decrease in the alpha-helical content of the protein.
      Phosphorylated CaM is very prone to dephosphorylation and was thus tested as a
      substrate for several phosphatases. It was unaffected by calcineurin (PP2B), but
      was a reasonable substrate for the pleiotropic phosphatases PP1gamma and PP2A.

PMID- 9572871
TI  - A novel tetraester construct that reduces cationic lipid-associated cytotoxicity.
      Implications for the onset of cytotoxicity.
AB  - The preparation of cationic amphiphiles that induce minor cytotoxic response
      during polynucleotide delivery into mammalian cells has been limited by the
      conventional use of ester, amide, or carbamate linkages to tether either the
      polar or the hydrophobic domains. The deleterious effects of ammonium-based
      lipidic salts on cellular processes have been well-established. The present
      report is the first example of a linchpin tetraester construct that utilizes
      ester linkages to tether both the polar and hydrophobic domains. Dimyristoyl and
      dioleoyl analogues were prepared from pentaerythritol, N,N-dimethylglycine, and
      their corresponding fatty acyl groups via successive diesterifications followed
      by amine quaternization. The resultant cationic tetraesters were examined in
      transfection (luciferase) and cell proliferation (MTS) assays using NIH 3T3 and
      16HBE14o- cells. The tetraesters exhibited transfection activity comparable to
      the well-studied lipids DOTAP and DC-cholesterol (DC-chol) in both cell lines.
      The tetraester construct afforded no cytotoxicity in NIH3T3 cells and provided a
      significant lowering of cytotoxicity relative to DC-chol in the 16HBE14o- cells.
      The expression of green fluorescent protein (GFP) in both cell lines also was
      examined using the lipid panel. Comparison of fluorescent and corresponding phase
      contrast images confirmed the chemical cytotoxicity results and revealed that the
      cytotoxic response was not dependent on transgene expression. Phase-contrast
      micrographs of cells treated with the cationic lipid panel in the absence of GFP
      plasmid showed identical morphology to the GFP-transfected cells, suggesting that
      the onset of a lipid-mediated cytotoxic response might occur at a stage prior to
      endosomal encapsulation.

PMID- 9572872
TI  - Identification of the subunit and important target peptides of pig heart NAD
      dependent isocitrate dehydrogenase modified by the affinity label adenosine 5'-O
      [S-(4-bromo-2, 3-dioxobutyl)thiophosphate].
AB  - Pig heart NAD-dependent isocitrate dehydrogenase is inactivated by adenosine 5'-O
      [S-(4-bromo-2,3-dioxobutyl)thiophosphate] (AMPS-BDB) with incorporation of 1.78
      mol of reagent/mol of average subunit. Complete protection against the
      inactivation is provided by 20 mM isocitrate + 1 mM Mn2+, and the incorporation
      is decreased to about 1.3 mol of reagent/mol of average subunit. The addition of
      NAD, NADH, or Mn2+ alone has little effect on the functional changes produced by
      AMPS-BDB, while ADP gives only partial protection against the inactivation. The
      ability of ADP to decrease the Km for isocitrate is not affected by the AMPS-BDB
      modification of the enzyme. These results indicate that the isocitrate substrate
      site is the target of AMPS-BDB. The enzyme has three types of subunits with a
      tetramer having the composition alpha2 beta gamma. Here, [2-3H]AMPS-BDB-modified
      subunits are separated by HPLC on a C4 reverse-phase column, after the treatment
      of the modified enzyme with 4 M urea. The predominant radioactivity is
      distributed in alpha and gamma subunits. However, evidence based on recombination
      of subunits from modified and unmodified enzymes indicates that only labeling of
      the alpha subunit is responsible for inactivation by AMPS-BDB. Subsequently, the
      separated modified subunits were chemically cleaved by CNBr and then purified by
      HPLC using a C18 column. The labeled peptides were further digested by pepsin,
      purified by HPLC, and sequenced. These results indicate that R88 and R98 from the
      alpha subunit are the major targets of AMPS-BDB which cause inactivation and that
      these are at or near the isocitrate site of the enzyme.

PMID- 9572873
TI  - Reaction of dopa decarboxylase with alpha-methyldopa leads to an oxidative
      deamination producing 3,4-dihydroxyphenylacetone, an active site directed
      affinity label.
AB  - Dopa decarboxylase (DDC) catalyzes the cleavage of alpha-methylDopa into 3,4
      dihydroxyphenylacetone and ammonia, via the intermediate alpha-methyldopamine,
      which does not accumulate during catalysis. The ketone has been identified by
      high-performance liquid chromatography and mass spectroscopic analysis, and
      ammonia by means of glutamate dehydrogenase. Molecular oxygen is consumed during
      the reaction in a 1:2 molar ratio with respect to the products. The kcat and Km
      of this reaction were determined to be 5.68 min-1 and 45 microM, respectively.
      When the reaction is carried out under anaerobic conditions, alpha-methyldopamine
      is formed in a time-dependent manner and neither ammonia nor ketone is produced
      to a significant extent. The reaction is accompanied by a time- and concentration
      dependent inactivation of the enzyme with kinact of 0. 012 min-1 and Ki of 39.3
      microM. Free 3,4-dihydroxyphenylacetone binds to the active site of DDC and
      inactivates the enzyme in a time- and concentration-dependent manner with a
      kinact/Ki value similar to that of alpha-methylDopa. d-Dopa, a competitive
      inhibitor of DDC, protects the enzyme against inactivation. Taken together, these
      findings indicate the active site directed nature of the interaction of DDC with
      3,4-dihydroxyphenylacetone and provide evidence that the ketone generated by the
      reaction of DDC with alpha-methylDopa dissociates from the active site before it
      inactivates the enzyme. Inactivation of the enzyme by ketone followed by NaB3H4
      reduction and chymotryptic digestion revealed that the lysine residue which binds
      pyridoxal 5'-phosphate (PLP) in the native enzyme is the site of covalent
      modification. Together with the characterization of the adduct released from the
      inactivated DDC, these data suggest that the enzyme is inactivated by trapping
      the coenzyme in a ternary adduct with ketone and the active site lysine. As
      recently reported for serotonin (5-HT) [Bertoldi, M., Moore, P. S., Maras, B.,
      Dominici, P., and Borri Voltattorni, C. (1996) J. Biol. Chem. 271, 23954-23959],
      the conversion of dopamine (DA) into 3,4-dihydroxyphenylacetaldehyde and ammonia
      catalyzed by DDC is accompanied by irreversible loss of decarboxylase activity.
      However, the comparison between the absorbance, fluorescence, and CD features of
      DDC after 5-HT- or 3, 4-dihydroxyphenylacetone-induced inactivation shows that a
      different covalent adduct is formed between either of these two molecules and DDC
      bound PLP.

PMID- 9572874
TI  - Model studies on calcium-containing quinoprotein alcohol dehydrogenases.
      Catalytic role of Ca2+ for the oxidation of alcohols by coenzyme PQQ (4,5-dihydro
      4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2, 7,9-tricarboxylic acid).
AB  - Mechanistic studies on the action of calcium-containing quinoprotein alcohol
      dehydrogenases have been performed by using a series of PQQ model compounds in
      anhydrous organic media. The PQQ model compounds are shown to form 1:1 complexes
      with a series of alkaline earth metal ions by spectroscopic methods and
      theoretical calculations. The site of coordination of the PQQ molecule to the
      metal ions in solution is indicated to be the same as in the case of enzymatic
      systems. It has also been found that Ca2+ binds to the quinone most strongly
      among the alkaline earth metal ions. Formation of the C-5 hemiacetal derivatives
      with methanol, ethanol, and 2-propanol is also investigated
      spectrophotometrically to show that the alcohol addition to the quinone is
      enhanced in the presence of the metal ions. In this case as well, Ca2+ shows the
      highest efficiency for the enhancement of the C-5 hemiacetal formation. Addition
      of a strong base such as DBU into an MeCN solution containing the Ca2+ complex of
      the PQQ model compounds and the alcohols leads to the redox reactions to afford
      reduced PQQ derivatives and the corresponding aldehydes. On the basis of detailed
      kinetic studies on the redox reactions, including structural effects of PQQ
      analogues and metal ion effects, we propose the addition-oxidative elimination
      mechanism through the C-5 hemiacetal intermediate.

PMID- 9572875
TI  - Identification of O-glycosylation sites and partial characterization of
      carbohydrate structure and disulfide linkages of human insulin-like growth factor
      binding protein 6.
AB  - The actions of insulin-like growth factors (IGFs) are modulated by a family of
      high-affinity binding proteins (IGFBPs), including IGFBP-6, which preferentially
      binds IGF-II and is O-glycosylated. Glycosylated and nonglycosylated recombinant
      human IGFBP-6, expressed in Chinese hamster ovary cells and Escherichia coli,
      respectively, were purified using IGF-II affinity chromatography and reverse
      phase medium-pressure chromatography. Electrospray ionization mass spectrometry
      (ESMS) of glycosylated IGFBP-6 revealed considerable heterogeneity of
      carbohydrate composition. Major glycoforms contained 8-16 monosaccharides,
      including N-acetylhexosamine, hexose, and N-acetylneuraminic acid. Glycosylation
      sites of IGFBP-6 were identified as Thr126, Ser144, Thr145, Thr146, and Ser152 by
      using a combination of ESMS and Edman sequencing of tryptic fragments separated
      by reverse-phase high-pressure liquid chromatography. One oligosaccharide chain
      contained 5-6 monosaccharides, whereas the others contained 2-4 monosaccharides.
      Glycosylated IGFBP-6 exhibited greater resistance to proteolysis by chymotrypsin
      and trypsin than nonglycosylated IGFBP-6. Native disulfide bond positions in
      IGFBP-6 were localized by means of observed disulfide-linked tryptic fragments,
      revealing that there are two disulfide-linked subdomains within each of the N-
      and C-terminal regions and confirming a previous suggestion that the latter
      regions are not interconnected. A model of IGFBP-6 is developed in which these
      distinct domains are separated by a central region which is O-glycosylated.

PMID- 9572876
TI  - Folding of firefly (Photinus pyralis) luciferase: aggregation and reactivation of
      unfolding intermediates.
AB  - The guanidine-induced unfolding of firefly (Photinus pyralis) luciferase involves
      two inactive equilibrium intermediates and is freely reversible at low protein
      concentration and low temperature. However, reactivation is exceedingly slow so
      that the equilibrium is attained only after several days of incubation and
      reactivation yields decrease strongly with increasing protein concentration,
      suggesting that aggregation is a competing side reaction [Herbst et al. (1997) J.
      Biol. Chem. 272, 7099-7105]. We investigated the role of the equilibrium
      intermediates in the aggregation process using size-exclusion chromatography and
      dynamic light scattering to monitor their association state. Although the more
      unfolded intermediate aggregated much more rapidly, both intermediates associated
      irreversibly without a conformational change visible by fluorescence or circular
      dichroism, forming small oligomers which remained soluble in the presence of the
      denaturant. The association kinetics are compatible with a nucleated
      polymerization mechanism. Unfolding kinetics at 1 M denaturant indicated the
      presence of a further inactive intermediate capable to reactivate rapidly with
      kinetics similar to those observed for luciferase reactivation in the presence of
      cell extracts. The data suggest a kinetic trap in luciferase refolding that is
      accessible from both equilibrium intermediate conformations and is avoided in the
      presence of molecular chaperones.

PMID- 9572877
TI  - A hierarchy of disulfide-bonded subunits: the quaternary structure of Eudistylia
      chlorocruorin.
AB  - The quaternary structure of the cysteine-rich, approximately 3500-kDa
      chlorocruorin (Chl) from the marine polychaete Eudistylia vancouverii was
      investigated using maximum entropy deconvolution of the electrospray ionization
      mass spectra (ESIMS). The native Chl provided two groups of peaks, at
      approximately 25 and approximately 33 kDa, and one peak at approximately 66 kDa.
      ESIMS of the reduced and reduced and carbamidomethylated Chl and of its subunits
      obtained by HPLC provided the complete subunit composition of the Chl. Two groups
      of nonglobin linker chains were observed: L1a-f (25 000.4, 25 017.9, 25 039.6, 25
      057.0, 25 074.4 and 25 096.8 Da) and L2a-d (25 402.7, 25 446.0, 25 461.6 and 25
      478.3Da) (+/-2.5 Da), with relative intensities L1:L2 = 5:2. Six globin chains
      were found, a1, a2, and b1-4, with reduced masses of 16 051.5, 16 172.4, 16
      853.5, 17 088.9, 17 161.2 and 17 103.6 (+/-1.0 Da) and relative intensities of
      8:4:1:4:2:1, respectively. Disulfide-bonded dimers and a tetramer of globin
      chains were identified: D1 = a1 + b3 at 33 207.1; D2 at 33 374.1, which had a
      cysteinylated Cys (a2 + b2 + Cys); and D3 = a1 + b4 at 33 149.4 Da (+/-3.0 Da),
      with relative intensities D1:D2:D3 = 5:4:1 and T = a1 + a2 + b1 + b2 at 66 154.8
      +/- 4.0 Da. A 206-kDa dodecamer subunit obtained by dissociation of the Chl in 4
      M urea [Qabar, A. N., et al. (1991) J. Mol. Biol. 222, 1109-1129], was found to
      consist only of tetramers T. A model was proposed for the Chl, based on a
      dimer:tetramer ratio of 2:1: four 206-kDa dodecamers (trimer of tetramers) and 48
      dimers tethered to a framework of 30 L1 and 12 L2 linker chains. The 144 globin
      chains (2480 kDa) and 42 linker chains (1059 kDa) provide a total mass of 3539
      kDa, in good agreement with the 3480 +/- 225 kDa determined previously by STEM
      mass mapping. The hierarchy of disulfide-bonded globin subunits observed for
      Eudistylia Chl provides a built-in heterogeneity of hexagonal bilayer structures.

PMID- 9572879
TI  - Affinity of fatty acid for rRat intestinal fatty acid binding protein: further
      examination 

PMID- 9572878
TI  - Thermal unfolding of three acclimation temperature-associated isoforms of carp
      light meromyosin expressed by recombinant DNAs.
AB  - Differential scanning calorimetry (DSC) was performed to investigate
      thermodynamic properties of three carp fast skeletal light meromyosin (LMM)
      isoforms expressed in Escherichia coli by recombinant DNAs. Three isoforms were
      the 10 degreesC-, intermediate-, and 30 degreesC-type LMM predominantly expressed
      in carp acclimated to 10, 20, and 30 degreesC. The isoforms expressed in E. coli
      by recombinant DNAs exhibited a typical pattern of alpha-helix in CD spectroscopy
      with two minima at 222 and 208 nm. Moreover, the three isoforms formed
      paracrystals typical of LMM, suggesting that expressed proteins retained intact
      structural properties. When the LMM isoforms were subjected to DSC analysis, the
      10 degreesC and 30 degreesC types showed endotherms having transition
      temperatures (Tm) at 35.1 and 39.5 degreesC, respectively, which are responsible
      for thermal unfolding of alpha-helix. The intermediate type exhibited two
      comparable endotherms with Tm values at 34.9 and 40.6 degreesC, implying that it
      has intermediate thermodynamic properties between those of 10 degreesC and 30
      degreesC types. However, a chimeric LMM having the 10 degreesC and 30 degreesC
      type as N- and C-terminal halves, respectively, showed the DSC pattern typical of
      the whole 30 degreesC-type molecule. On the other hand, another chimeric LMM
      composed of the N-terminal 30 degreesC type and C-terminal 10 degreesC type gave
      the pattern of the full 10 degreesC type. These results suggest that
      thermodynamic properties of the C-terminal half largely account for thermal
      unfolding of the whole molecule.

PMID- 9572880
TI  - 1'-Benzyl-3,4-dihydrospiro[2H-1- benzothiopyran-2,4'-piperidine] (spipethiane), a
      potent and highly selective sigma1 ligand.

PMID- 9572881
TI  - Potent, selective, and orally bioavailable tricyclic pyridyl acetamide N-oxide
      inhibitors of farnesyl protein transferase with enhanced in vivo antitumor
      activity.
AB  - We previously reported compound 1 as a potent farnesyl protein transferase (FPT)
      inhibitor that exhibited reasonable pharmacokinetic stability and showed moderate
      in vivo activity against a variety of tumor cell lines. The analogous C-11 single
      compound, pyridylacetamide 2, was found to be more potent than 1 in FPT
      inhibition. Further studies showed that modification of the ethano bridge of the
      tricyclic ring system by conversion into a double bond with concomitant
      introduction of a single bond at C-11 piperidine resulted in compound 3 that had
      superior FPT activity and pharmacokinetic stability. Compound 4, a 5-bromo
      substituted analogue of 3, showed improved FPT activity, had good cellular
      activity, and demonstrated a remarkably improved pharmacokinetic profile with AUC
      of 84.9 and t1/2 of 82 min. Compound4 inhibited the growth of solid tumor in DLD
      1 model by 70% at 50 mpk and 52% at 10 mpk.

PMID- 9572882
TI  - 5-(5,6-Dichloro-2-indolyl)-2-methoxy-2,4-pentadienamides: novel and selective
      inhibitors of the vacuolar H+-ATPase of osteoclasts with bone antiresorptive
      activity.
AB  - The vacuolar H+-ATPase (V-ATPase), located on the ruffled border of the
      osteoclast, is a proton pump which is responsible for secreting the massive
      amounts of protons that are required for the bone resorption process. With the
      aim to identify new agents which are able to prevent the excessive bone
      resorption associated with osteoporosis, we have designed a novel class of potent
      and selective inhibitors of the osteoclast proton pump, starting from the
      structure of the specific V-ATPase inhibitor bafilomycin A1. Compounds 3a-d
      potently inhibited the V-ATPase in chicken osteoclast membranes (IC50 = 60-180
      nM) and were able to prevent bone resorption by human osteoclasts in vitro at low
      nanomolar concentrations. Notably, the EC50 of compound 3c in this assay was 45
      fold lower than the concentration required for half-maximal inhibition of the V
      ATPase from human kidney cortex. These results support the validity of the
      osteoclast proton pump as a useful molecular target to produce novel inhibitors
      of bone resorption, potentially useful as antiosteporotic agents.

PMID- 9572883
TI  - (+)-cis-N-ethyleneamino-N-normetazocine derivatives. Novel and selective sigma
      ligands with antagonist properties.
AB  - A series of (+)-cis-N-normetazocine derivatives has been described, and their
      affinities for sigma1, sigma2, and phencyclidine (PCP) sites and opioid,
      muscarinic (M2), dopamine (D2), and serotonin (5-HT2) receptors were evaluated.
      The effect of the N-substitution with a substituted ethylamino spacer was
      investigated. Compounds 8c-11c displayed high affinities for sigma1 sites and for
      opioid receptors. Substitution of the second basic nitrogen either with alkyl or
      cycloalkyl substituents give compounds (1a-6a) with high affinity and selectivity
      for sigma1 binding sites. Compounds 1a-5a were further characterized in vivo, and
      their agonist/antagonist activity was evaluated. In mouse, compound 1a and 2a as
      well as haloperidol suppressed in a dose-related manner the stereotyped behavior
      induced by (+)-SKF 10,047. Compounds 3a-5a and (+)-pentazocine do not affect the
      stereotyped behavior induced by ip injection of (+)-SKF 10,047. Therefore, from
      this series of compounds we identified potent and selective sigma1 ligands which
      might prove useful to unveil the functional role of sigma1 sites.

PMID- 9572884
TI  - Cyclopropane-derived peptidomimetics. Design, synthesis, evaluation, and
      structure of novel HIV-1 protease inhibitors.
AB  - Toward establishing the general efficacy of using trisubstituted cyclopropanes as
      peptide mimics to stabilize extended peptide structures, the cyclopropanes 20a-d
      were incorporated as replacements into 9-13, which are analogues of the known HIV
      1 protease inhibitors 14 and 15. The syntheses of 20a-d commenced with the
      Rh2[5(S)-MEPY]4-catalyzed cyclization of the allylic diazoesters 16a-d to give
      the cyclopropyl lactones 17a-d in high enantiomeric excess. Opening of the
      lactone moiety using the Weinreb protocol and straightforward refunctionalization
      of the intermediate amides 18a-d gave 20a-d. A similar sequence of reactions was
      used to prepare the N-methyl-2-pyridyl analogue 28. Coupling of 20a-d and 28 with
      the known diamino diol 22 delivered 9-13. Pseudopeptides 9-12 were found to be
      competitive inhibitors of wild-type HIV-1 protease in biological assays having
      Kis of 0.31-0.35 nM for 9, 0.16-0.21 nM for 10, 0.47 nM for 11, and 0.17 nM for
      12; these inhibitors were thus approximately equipotent to the known inhibitor
      14(IC50 = 0.22 nM) from which they were derived. On the other hand 13 (Ki = 80
      nM) was a weaker inhibitor than its analogue 15 (Ki = 0.11 nM). The solution
      structures of 9 and 10 were analyzed by NMR spectroscopy and simulated annealing
      procedures that included restraints derived from homo- and heteronuclear coupling
      constants and NOEs; because of the molecular symmetry of9 and 10, a special
      protocol to treat the NOE data was used. The final structure was checked by
      restrained and free molecular dynamic calculations using an explicit DMSO solvent
      box. The preferred solution conformations of 9 and 10 are extended structures
      that closely resemble the three-dimensional structure of 10 bound to HIV-1
      protease as determined by X-ray crystallographic analysis of the complex. This
      work convincingly demonstrates that extended structures of peptides may be
      stabilized by the presence of substituted cyclopropanes that serve as peptide
      replacements. Moreover, the linear structure enforced in solution by the two
      cyclopropane rings in the pseudopeptides 9-12 appears to correspond closely to
      the biologically active conformation of the more flexible inhibitors 14 and 15.
      The present work, which is a combination of medicinal, structural, and quantum
      chemistry, thus clearly establishes that cyclopropanes may be used as structural
      constraints to reduce the flexibility of linear pseudopeptides and to help
      enforce the biologically active conformation of such ligands in solution.

PMID- 9572885
TI  - Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic
      agents: synthesis, quantitative structure-activity relationships, and molecular
      modeling of substituted 1-(3-pyridylcarbamoyl)indolines.
AB  - The synthesis, biological activity, and molecular modeling of a novel series of
      substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are
      isosteres of the previously published indole urea 1 (SB-206553) and illustrate
      the use of aromatic disubstitution as a replacement for fused five-membered rings
      in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space
      previously identified as sterically allowed at the 5-HT2C receptor but disallowed
      at the 5-HT2A receptor, we have identified a number of compounds which are the
      most potent and selective 5-HT2C/2B receptor antagonists yet reported. 46 (SB
      221284) was selected on the basis of its overall biological profile for further
      evaluation as a novel, potential nonsedating anxiolytic agent. A CoMFA analysis
      of these compounds produced a model with good predictive value and in addition
      good qualitative agreement with both our 5-HT2C receptor model and our proposed
      binding mode for this class of ligands within that model.

PMID- 9572886
TI  - Synthesis and adrenergic activity of a new series of N-aryl dicyclopropyl ketone
      oxime ethers: SAR and stereochemical aspects.
AB  - A novel series of 31 N-aryl dicyclopropyl ketone oxime ethers were synthesized
      and tested for their activity at alpha- and beta-adrenergic receptors. All of the
      compounds showed greater affinity for beta-than for alpha1-receptor sites. Some
      compounds had pure antagonist effects whereas some were partial agonists. Several
      compounds had an antagonist effect matching that of propranolol in in vitro
      (binding data and pA2 values on rat heart ventricle homogenates and guinea pig
      spontaneously beating right and electrically driven left atrial isolated
      preparations, respectively) and in in vivo tests (measurement of antagonism
      toward isoprenaline-induced tachycardia in anesthetized rats). Furthermore, all
      of the compounds showed a beta1-adrenergic selectivity (beta2-affinity > 1500
      nM).

PMID- 9572887
TI  - Novel euglycemic and hypolipidemic agents. 1.
AB  - A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been
      synthesized by the condensation of corresponding aldehyde 1 and 2,4
      thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2
      and its saturated counterpart 3 have shown antihyperglycemic activity. Many of
      these compounds have shown superior euglycemic and hypolipidemic activity
      compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to
      be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese
      C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution
      studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are
      well-distributed in target tissues. On the basis of euglycemic activity as well
      as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189
      (3g) has been selected for further evaluation.

PMID- 9572888
TI  - Syntheses and biological evaluation of indolocarbazoles, analogues of
      rebeccamycin, modified at the imide heterocycle.
AB  - A series of 10 indolocarbazole derivatives, analogues to the antitumor antibiotic
      rebeccamycin, bearing modifications at the imide heterocycle were synthesized.
      They bear an N-methyl imide, N-methyl amide, or anhydride function instead of the
      original imide. Their inhibitory potencies toward topoisomerase I were examined
      using a DNA relaxation assay and by analyzing the drug-induced cleavage of 32P
      labeled DNA. Protein kinase C (PKC) inhibition and interaction with DNA were also
      studied together with the in vitro antiproliferative activities against B16
      melanoma and P388 leukemia cells. The antimicrobial activities against two Gram
      positive bacteria (Bacillus cereus and Streptomyces chartreusis), a Gram-negative
      bacterium (Escherichia coli), and a yeast (Candida albicans) were tested as well
      as their antiviral activities toward HIV-1. The efficiency of the anhydride
      compounds was compared to that of the parent compound rebeccamycin and its
      dechlorinated analogue. All the compounds studied were inactive against PKC. The
      structural requirements for PKC and topoisomerase I inhibition are markedly
      different. In sharp contrast with the structure-PKC inhibition relationships, we
      found that an anhydride function does not affect topoisomerase I inhibition,
      whereas a methyl group on the indole nitrogen prevents the poisoning of
      topoisomerase I. The compounds exhibiting a marked toxicity to P388 leukemia
      cells had little or no effect on the growth of P388CPT5 cells which are resistant
      to the topoisomerase I inhibitor camptothecin. This study reinforces the
      conclusion that the DNA-topoisomerase I cleavable complex is the primary cellular
      target of the indolocarbazoles and significantly contributes to their
      cytotoxicity and possibly to their weak but noticeable anti-HIV-1 activities. The
      structure-activity relationships are also discussed.

PMID- 9572889
TI  - Synthesis and biology of the conformationally restricted ACPD analogue, 2
      aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I, a potent mGluR agonist.
AB  - To better characterize the roles of metabotropic glutamate receptors (mGluRs) in
      physiological and pathophysiological processes, there is an important need to
      learn more about the structural features relevant to the design of novel, high
      affinity ligands that are family and subtype specific. To date, many of the
      biological studies that have been conducted in the area of mGluR research have
      made use of the agonist (1S,3R)-ACPD. This compound has been shown to act as an
      agonist at both the group I and group II receptors while showing little
      selectivity among the four subtypes belonging to these two groups. Moreover,
      (1S,3S)-ACPD, the cis isomer, shows negligible activity at group I receptors and
      is a good agonist of mGluR2. Since ACPD is itself somewhat flexible, with four
      distinctive conformations being identified from molecular modeling studies for
      the trans isomer and five conformations for the cis isomer, we believed that it
      would be of interest to examine the activity of an ACPD analogue that has been
      constrained through the introduction of a single carbon atom bridge. Accordingly,
      we have prepared an aminobicyclo[2.1.1]hexanedicarboxylic acid (ABHxD-I) analogue
      of ACPD. The synthesis of this compound was accomplished by use of an
      intramolecular [2 + 2] photocycloaddition reaction, in which four distinct
      isomers were isolated. Of these four compounds, only a single isomer, ABHxD-I
      (6a), was found to be a potent agonist of the mGluRs. This compound, which
      expresses the fully extended glutamate conformation, was found to be more potent
      than ACPD at all six of the eight mGluR subtypes that were investigated and to be
      comparable to or more potent than the endogenous ligand, glutamate, for these
      receptors. Interestingly, despite its fixed conformation, ABHxD-I, like
      glutamate, shows little subtype selectivity. Through modeling studies of ABHxD-I
      (6a), ABHD-VI, LY354740, (1S,3R)-ACPD, (1S, 3S)-ACPD, and l-glutamate, we
      conclude that the aa conformation of l-glutamate is the active conformation for
      both group I and group II mGluRs. Moreover, the modeling-based comparisons of
      these ligands suggest that the selectivity exhibited by LY354740 between the
      group I and group II mGluRs is not a consequence of different conformations of L
      glutamate being required for recognition at these mGluRs but rather is related to
      certain structural elements within certain regions having a very different impact
      on the group I and group II mGluR activity. The enhanced potency of ABHxD-I
      relative to trans-ACPD commends it as a useful starting point in the design of
      subtype selective mGluR ligands.

PMID- 9572890
TI  - Anhydrolide macrolides. 1. Synthesis and antibacterial activity of 2,3-anhydro-6
      O-methyl 11,12-carbamate erythromycin A analogues.
AB  - A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-carbamate
      analogues have been synthesized and evaluated for antibacterial activity. These
      compounds were found to be potent antibacterial agents against Gram-positive
      organisms in vitro, many having MIC values below 1 microg/mL for the macrolide
      susceptible Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus
      pneumoniae, as well as improved activity compared to erythromycin A against the
      inducibly MLS (macrolide, lincosamide, and streptogramin B)-resistant organisms.
      Structure-activity studies revealed that arylalkyl carbamates with two and four
      carbon atoms between the aromatic moiety and carbamate nitrogen have the best in
      vitro activity. All of the C-10 epi analogues evaluated were found to have
      substantially less activity than the corresponding natural C-10 isomer. Several
      analogues demonstrated moderate antibacterial activity against the constitutively
      resistant S.aureus A-5278, S. pneumoniae5979, and S.pyogenes 930. However,
      despite potent in vitro activity, these analogues showed only moderate in vivo
      activity in mouse protection studies.

PMID- 9572891
TI  - Anhydrolide macrolides. 2. Synthesis and antibacterial activity of 2,3-anhydro-6
      O-methyl 11,12-carbazate erythromycin A analogues.
AB  - A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-cyclic
      carbazate analogues was prepared and evaluated for antibacterial activity. These
      2,3-anhydro macrolides were found to be potent antibacterial agents in vitro
      against macrolide-susceptible organisms including Staphylococcus aureus 6538P,
      Streptococcus pyogenes EES61, and Streptococcuspneumoniae ATCC6303. These
      compounds were also very active against some organisms that show macrolide
      resistance (S. aureus A5177, S. pyogenes PIU2584, and S. pneumoniae 5649). The
      compounds generally showed poor activity against organisms with constitutive MLS
      resistance. Selected compounds were evaluated in vivo in mouse protection
      studies. Although most of the compounds tested in vivo showed poor efficacy, two
      compounds, 38 and 57, were more active than clarithromycin against S. pneumoniae
      ATCC6303.

PMID- 9572892
TI  - Modular fluorescent-labeled siderophore analogues.
AB  - Biomimetic analogues 1 of the microbial siderophore (iron carrier) ferrichrome
      were labeled via piperazine with various fluorescent markers at a site not
      interfering with iron binding or receptor recognition (compounds 10-12). These
      iron carriers were built from a tetrahedral carbon symmetrically extended with
      three strands, each containing an amino acid (G = glycyl, A = alanyl, L = leucyl
      and P = phenylalanyl) and terminated by a hydroxamic acid, which together define
      an octahedral iron-binding domain. A fourth exogenous strand provided the site
      for connecting various fluorescent markers via a short bifunctional linker.
      Iron(III) titrations, along with fluorescence spectroscopy, generated quenching
      of fluorescence emission of some of the probes used. The quenching process fits
      the Perrin model which reinforces the intramolecular quenching process,
      postulated previously.1 All tested compounds, regardless of their probe size,
      polarity, or the linker binding them to the siderophore analogue, promote growth
      of Pseudomonas putida with the same efficacy as the nonlabeled analogues 1, with
      the added benefit of signaling microbial activity by fluorescence emission. All G
      derivatives of compounds 10-12 were found to parallel the behavior of natural
      ferrichrome, whereas A derivatives mediated only a modest iron(III) uptake by P.
      putida. Incubation of various Pseudomonas strains with iron(III)-loaded G
      derivatives resulted in the build-up of the labels' fluorescence in the culture
      medium to a much larger extent than from the corresponding A derivatives. The
      fluorescence buildup corresponds to iron utilization by the cells and the release
      of the fluorescent labeled desferrisiderophore from the cell to the media. The
      fact that the microbial activity of these compounds is not altered by attachment
      of various fluorescent markers via a bifunctional linker proposes their
      application as diagnostic tools for detecting and identifying pathogenic
      microorganisms.

PMID- 9572893
TI  - Conformationally defined retinoic acid analogues. 4. Potential new agents for
      acute promyelocytic and juvenile myelomonocytic leukemias.
AB  - We recently synthesized several conformationally constrained retinoic acid (RA)
      analogues [8-(2'-cyclohexen-1'-ylidene)-3, 7-dimethyl-2,4,6-octatrienoic acids
      with different alkyl substituents at 2' (R1) and 3' (R2) positions on the
      cyclohexene ring] (Muccio et al. J. Med. Chem. 1996, 39, 3625) as cancer
      chemopreventive agents. UAB8 (R1 = Et; R2 = iPr), which contains sufficient
      steric bulk at the terminal end of the polyene chain to mimic the
      trimethylcyclohexenyl ring of RA, displayed biological properties similar to
      those of RA. To explore the efficacy of this retinoid in acute promyelocytic
      leukemia (APL) and juvenile myelomonocytic leukemia (JMML), we evaluated UAB8
      isomers in in vitro assays which measure the capacity of retinoids to inhibit
      aberrant myeloid colony growth from blood or bone marrow cells obtained from
      human JMML patients and in assays measuring the potential of retinoids to
      differentiate NB4 cells (an APL cell line). Both (all-E)- and (13Z)-UAB8 were 2
      fold more active than RA in the NB4 cell differentiation assay; however, only
      (all-E)-UAB8 had comparable activity to the natural retinoids in the JMML cell
      assays. These results were compared to the biological effectiveness of a new
      retinoid, UAB30 [8-(3', 4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl
      2,4, 6-octatrienoic acid], which had different nuclear receptor binding and
      transactivational properties than UAB8. Relative to (all-E)-RA and (all-E)-UAB8,
      (all-E)-UAB30 bound well to RARalpha but did not activate transcription-mediated
      RARalpha homodimers, even though it was effective in RARbeta- and RARgamma
      mediated transactivational assays. In APL assays, this retinoid had much reduced
      activity and was only moderately effective in JMML assays and in cancer
      chemoprevention assays.

PMID- 9572894
TI  - Antineoplastic agents. 379. Synthesis of phenstatin phosphate.
AB  - A structure-activity relationship (SAR) study of the South African willow tree
      (Combretum caffrum) antineoplastic constituent combretastatin A-4 (1b) directed
      at maintaining the (Z)-stilbene relationship of the olefin diphenyl substituents
      led to synthesis of a potent cancer cell growth inhibitor designated phenstatin
      (3b). Initially phenstatin silyl ether (3a) was unexpectedly obtained by Jacobsen
      oxidation of combretastatin A-4 silyl ether (1c --> 3a), and the parent
      phenstatin (3b) was later synthesized (6a --> 3a --> 3b) in quantity. Phenstatin
      was converted to the sodium phosphate prodrug (3d) by a dibenzyl phosphite
      phosphorylation and subsequent hydrogenolysis sequence (3b --> 3c --> 3d).
      Phenstatin (3b) inhibited growth of the pathogenic bacterium Neisseriagonorrhoeae
      and was a potent inhibitor of tubulin polymerization and the binding of
      colchicine to tubulin comparable to combretastatin A-4 (1b). Interestingly, the
      prodrugs were found to have reduced activity in these biochemical assays. While
      no significant tubulin activity was observed with the phosphorylated derivative
      of combretastatin A-4 (1d), phosphate 3d retained detectable inhibitory effects
      in both assays.

PMID- 9572895
TI  - Inhibition of human alcohol dehydrogenases by formamides.
AB  - Human alcohol dehydrogenase (HsADH) comprises class I (alpha, beta, and gamma),
      class II (pi), and class IV (sigma) enzymes. Selective inhibitors of the enzymes
      could be used to prevent the metabolism of alcohols that form toxic products.
      Formamides are unreactive analogues of aldehydes and bind to the enzyme-NADH
      complex [Ramaswamy, S.; Scholze, M.; Plapp, B. V. Biochemistry 1997, 36, 3522
      3527]. They are uncompetitive inhibitors against varied concentrations of
      alcohol, and this makes them effective even with saturating concentrations of
      alcohols. Molecular modeling led to the design and synthesis of a series of
      cyclic, linear, and disubstituted formamides. Evaluation of 23 compounds provided
      structure-function information and selective inhibitors for the enzymes, which
      have overlapping but differing substrate specificities. Monosubstituted
      formamides are good inhibitors of class I and II enzymes, and disubstituted
      formamides are selective for the alpha enzyme. Selective inhibitors, with Ki
      values at pH 7 and 25 degrees C of 0.33-0.74 microM, include N-cyclopentyl-N
      cyclobutylformamide for HsADH alpha, N-benzylformamide for HsADH beta1, N-1
      methylheptylformamide for HsADH gamma2, and N-heptylformamide for HsADH sigma and
      HsADH beta1.

PMID- 9572896
TI  - Isosteric analogues of nicotinamide adenine dinucleotide derived from furanfurin,
      thiophenfurin, and selenophenfurin as mammalian inosine monophosphate
      dehydrogenase (type I and II) inhibitors.
AB  - Dinucleotides TFAD (6), FFAD (7), and SFAD (8), isosteric NAD analogues derived,
      respectively, from C-nucleosides 5-beta-d-ribofuranosylthiophene-3-carboxamide
      (thiophenfurin, 1), 5-beta-d-ribofuranosylfuran-3-carboxamide (furanfurin, 2),
      and 5-beta-d-ribofuranosylselenophene-3-carboxamide (selenophenfurin, 5), were
      synthesized as human inosine monophosphate dehydrogenase (IMPDH) type I and II
      inhibitors. The synthesis was carried out by imidazole-catalyzed coupling of the
      5'-monophosphate of 1, 2, and 5 with AMP. These dinucleotides, which are also
      analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) and selenazole-4
      carboxamide adenine dinucleotide (SAD), the active metabolites of the oncolytic C
      nucleosides 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) and 2-beta
      D-ribofuranosylselenazole-4-carboxamide (selenazofurin), were evaluated for their
      inhibitory potency against recombinant human IMPDH type I and II. The order of
      inhibitory potency found was SAD > SFAD = TFAD = TAD >> FFAD for both enzyme
      isoforms. No significant difference was found in inhibition of IMPDH type I and
      II.

PMID- 9572897
TI  - 2'-C-Methyl analogues of selective adenosine receptor agonists: synthesis and
      binding studies.
AB  - 2'-C-Methyl analogues of selective adenosine receptor agonists such as (R)-PIA,
      CPA, CCPA, NECA, and IB-MECA were synthesized in order to further investigate the
      subdomain that binds the ribose moiety. Binding affinities of these new compounds
      at A1 and A2A receptors in bovine brain membranes and at A3 in rat testis
      membranes were determined and compared. It was found that the 2'-C-methyl
      modification resulted in a decrease of the affinity, particularly at A2A and A3
      receptors. When such modification was combined with N6-substitutions with groups
      which induce high potency and selectivity at A1 receptors, the high affinity was
      retained and the selectivity was increased. Thus, 2-chloro-2'-C-methyl-N6
      cyclopentyladenosine (2'-Me-CCPA), which displayed a Ki value of 1.8 nM at A1
      receptors, was selective for A1 vs A2A and A3 receptors by 2166- and 2777-fold,
      respectively, resulting in one of the most potent and A1-selective agonists so
      far known. In functional assay, this compound inhibited forskolin-stimulated
      adenylyl cyclase activity with an IC50 value of 13.1 nM, acting as a full
      agonist.

PMID- 9572898
TI  - A potent, orally bioavailable benzazepinone growth hormone secretagogue.
AB  - The identification of L-739,943 (8b), a potent, orally bioavailable benzolactam
      growth hormone secretagogue, is obtained from zwitterionic L-692,429 through
      modification of its amino acid side chain and replacement of the acidic 2'
      tetrazole with the neutral and potency enhancing 2'-(N
      methylaminocarbonylamino)methyl substituent. L-739,943 is orally active for the
      release of growth hormone in beagle dogs at doses as low as 0.5 mg/kg. Oral
      bioavailability in dogs of 8b is 24% at a dose of 2 mg/kg with a mean drug Cmax
      of 145 +/- 46 ng/mL. L-739,943 represents a significant breakthrough in terms of
      both potency and oral bioavailability as compared to the prototype benzolactam L
      692,429.

PMID- 9572899
TI  - Novel thieno[2,3-d][1,3]oxazin-4-ones as inhibitors of human leukocyte elastase.
AB  - A series of thieno[2,3-d][1,3]oxazin-4-ones was synthesized and evaluated in
      vitro for inhibitory activity toward human leukocyte elastase. New synthetic
      routes to 2-alkoxy-, 2-alkylthio-, and 2-sec-amino-substituted derivatives are
      reported. This study demonstrates the versatility of 2-aminothiophenes prepared
      by Gewald reaction as a synthetic entry to serine protease-inhibiting, fused 1,3
      oxazin-4-ones. Introduction of ethoxy, n-propoxy, and ethylthio groups at C-2
      delivered the most potent inhibitors of this series with Ki values lower than 11
      nM. Kinetic studies and product analyses revealed the formation of acyl-enzymes
      as a result of the attack of the active site serine at the carbon C-4 and
      subsequent deacylation. This mode of action is similar to the inhibition of
      serine proteases by 4H-3,1-benzoxazin-4-ones. Replacement of the benzene ring in
      benzoxazinones by a (substituted) thiophene led to improved hydrolytic stability
      and retained inhibitory potency.

PMID- 9572900
TI  - Scintigraphic evaluation of a new capsule-type colon specific drug delivery
      system in healthy volunteers.
AB  - Colonic drug delivery is intended for local or systemic therapies. The lack of
      predictive in vitro or animal model leads to considerable time delays in colonic
      product development. The objective of this scintigraphic study was to provide
      "proof of concept" for a novel capsule-type colonic delivery system (Colon
      Targeted Delivery Capsule) in healthy volunteers. The human data validates the
      design concept behind the release mechanism, in that capsule disintegration, and
      hence drug release, did not start until 5 h after gastric emptying, irrespective
      of whether the product was administered to fasted or fed subjects. However, the
      potential for prolonged gastric residence for large enteric coated products
      intended for intestinal targeting was also observed; overall, the study provides
      a focus for subsequent product development and highlights the role of
      scintigraphy in dynamically visualizing the drug delivery process.

PMID- 9572901
TI  - Formation of isomorphic desolvates: creating a molecular vacuum.
AB  - The objective of this work was to investigate a common but poorly understood
      category of crystalline organic substances: isomorphic desolvates. When solvent
      is lost from a crystal lattice but the lattice retains its three-dimensional
      order, a lattice is created which is in a high-energy state relative to the
      original solvate structure. The desolvated lattice can reduce its internal energy
      by either resorbing solvent or by relaxation processes which increase the packing
      efficiency of the solid by reducing the unit cell volume. In the following paper,
      solid-state properties of isomorphic desolvates of cephalexin, cefaclor,
      erythromycin A, and spirapril hydrochloride hydrates are investigated. The
      hygroscopicity of the compounds are evaluated using a vacuum moisture balance,
      and structural relaxation is measured using a combination of X-ray powder
      diffraction and isothermal microcalorimetry. The study results are explained in
      terms of Kitaigorodski's close packing principle.

PMID- 9572902
TI  - An investigation of FB interactions with poly(ethylene glycol) 6000,
      poly(ethylene glycol) 4000, and poly-epsilon-caprolactone by thermoanalytical and
      spectroscopic methods and modeling.
AB  - The interactions between flurbiprofen (FB) and different polymers are studied in
      order to improve the bioavailability of FB. FB-polymer phase diagrams
      [poly(ethylene glycol) (PEG) 4000, PEG 6000, and poly-epsilon-caprolactone] were
      constructed and compared with the modeling diagrams. Thermoanalytical methods
      (differential scanning calorimetry, thermomicroscopy) were used to construct the
      phase diagrams. Thermodynamic data were used to model the FB-polymer systems. The
      construction of the FB-polymer phase diagrams showed the existence of a stable
      invariant called "eutectic" characterized by (XE)exp, (TfE)exp, and
      (DeltaHfE)exp, the experimental eutectic composition, the experimental
      temperature, and the enthalpy of eutectic melting, respectively. Modeling
      confirmed the values for these parameters and was used to evaluate the different
      Flory-Huggins parameters chi for each FB-polymer mixture. chi values and the
      infrared spectra confirm that the interactions due to hydrogen bonds between FB
      and PEG 4000 are more numerous than between FB and PEG 6000 and also more
      numerous than between FB and poly-epsilon-caprolactone.

PMID- 9572903
TI  - Detection of suppression of bitterness by sweet substance using a multichannel
      taste sensor.
AB  - A multichannel taste sensor whose transducer is composed of several kinds of
      lipid/polymer membranes with different characteristics can detect taste in a
      manner similar to human gustatory sensation. Taste information is transformed
      into a pattern composed of electric signals of membrane potentials of the
      receptor part. In the present study, it was shown that the suppression of the
      bitterness of quinine and a drug substance by sucrose can be quantified using a
      multichannel taste sensor. The present method can be expected to provide a new
      automated method to measure the strength of bitterness of drug substance in the
      place of sensory evaluation.

PMID- 9572904
TI  - A study on gelatin capsule brittleness: moisture tranfer between the capsule
      shell and its content.
AB  - Variation in moisture content of the capsule shells either due to the change of
      storage conditions or the moisture transfer between the capsule shell and its
      contents may lead to undesired physical properties, such as capsule brittleness
      and stickiness. DMP 504, a developmental bile-acid sequestrant, is a strongly
      basic anion-exchange polymer which contains randomly distributed primary,
      secondary, tertiary, and quaternary amine groups in their hydrochoride salt form.
      The alkylammonium groups which comprise this polymer form a random network
      containing a high level of branching and a low level of cross-linking. DMP 504 is
      very hygroscopic and has a tendency to gain or lose moisture with ease. The
      transfer of moisture from the capsule shell to DMP 504 powder contained in a hard
      gelatin capsule can be expected, and if a low water content of the capsule shell
      is achieved, the capsules become brittle and fracture easily. The sorption
      isotherm for DMP 504 was generated by storing the drug substance under various
      relative humidity conditions. After equilibrium, the moisture contents for the
      samples of individual isotherm points were measured by thermogravimetric
      analyses. This report applies the sorption-desorption moisture transfer (SDMT)
      model to predict the equilibrium relative humidity in a system containing DMP 504
      in hard gelatin capsules and to establish target loss on drying values for DMP
      504 and the capsule shell. Application of this SDMT model resulted in finding a
      solution to the brittleness problem. The moisture levels of capsule shells and
      contents for two formulations in a 12-month stability program are also reported
      here. Results of this study further demonstrate that the SDMT model can be used
      as a tool to guide the formulator to select optimal initial moisture contents for
      the empty capsule shell and the formulation to avoid the incidence of brittle
      capsule problems.

PMID- 9572905
TI  - An investigation into the use of low-frequency dielectric spectroscopy as a means
      of characterizing the structure of creams based on Aqueous Cream BP.
AB  - A range of creams based on Aqueous Cream BP have been analyzed using low
      frequency dielectric spectroscopy, with accompanying circuit modeling in
      combination with rheological and microscopic supportive techniques, to explore
      the use of the dielectric approach as a novel means of characterizing cream
      systems. Creams based on the formula for Aqueous Cream BP were produced by hand
      mixing and mechanical mixing, with and without the inclusion of the preservative
      phenoxyethanol. Dielectric analysis was performed over a frequency range of 10(
      2)-10(5) Hz. Cream samples were also examined using stress scan rheology and
      differential interference contrast microscopy. Dielectric analysis indicated that
      the presence of preservative decreased the capacitance and loss of the creams.
      The responses were modeled in terms of a dispersive capacitance in series with
      two RC circuits (series and parallel). Rheological studies indicated higher
      viscosities for the hand-mixed and unpreserved systems. Differential interference
      contrast microscopy showed marked differences in the distribution of the oil
      droplets, depending on the method of mixing. The study has demonstrated that
      dielectric spectroscopy, with accompanying circuit analysis, may be used as a
      means of modeling the structure of cream systems. The investigation has also
      shown that the formulation and preparation method of Aqueous Cream BP may have a
      profound effect on sample structure.

PMID- 9572906
TI  - Is the pig a good animal model for studying the human ileal brake?
AB  - This study was designed to investigate the existence of an ileal brake mechanism
      in the pig model. The test substances used (oleic acid, deoxycholic acid,
      taurocholic acid) had all been previously shown to affect the ileal brake
      mechanism in other species including man. The substances were infused directly
      into the terminal ileum of surgically modified pigs, 45 min after the pigs had
      ingested a meal containing a drug marker. The marker used was sulfasalazine,
      which is cleaved to form a metabolite, sulfapyridine, when it reaches the colon.
      The subsequent HPLC analysis of collected blood samples allowed the appearance of
      sulfapyridine in the plasma and hence the arrival of sulfasalazine in the colon
      to be determined. Any differences in transit between control and test could be
      evaluated from a profile of plasma concentrations and corresponding values of
      AUC. The findings from this study show that the various substances did not affect
      transit of a test meal in the pig and suggest that it is not possible to use this
      pig model to make predictions about the human ileal brake.

PMID- 9572907
TI  - Absorption and intestinal metabolism of purine dideoxynucleosides and an
      adenosine deaminase-activated prodrug of 2',3'-dideoxyinosine in the mesenteric
      vein cannulated rat ileum.
AB  - This study investigates the mechanisms of absorption and the role of intestinally
      localized purine salvage pathway enzymes on the ileal availabilities of 2',3'
      dideoxyinosine (ddI), a substrate for purine nucleoside phosphorylase (PNP); 2'
      fluoro-2',3'-dideoxyinosine (F-ddI), a non-PNP substrate; and 6-chloro-2',3'
      dideoxypurine (6-Cl-ddP), an adenosine deaminase (ADA) activated prodrug of ddI.
      The potential for increasing the intestinal availability of 6-Cl-ddP through the
      use of ADA inhibitors, namely, 2'-deoxycoformycin (DCF) and erythro-9-(2-hydroxy
      3-nonyl)adenine (EHNA), is also explored. Drug permeability coefficients across
      the intestinal epithelium were determined in in situ perfusions in the mesenteric
      vein cannulated rat ileum based on both drug appearance in blood (Pblood) and
      disappearance from the lumen (Plumen) and their paracellular and transcellular
      components were estimated by comparison to the permeabilities of two paracellular
      markers, mannitol and urea. Values of Pblood for ddI were determined to be (1.1
      +/- 0.3) x 10(-6) cm/s, in close agreement with the value of (1.0 +/- 0.3) x 10(
      6) cm/s obtained for F-ddI, a PNP resistant analogue of ddI having virtually the
      same molecular size and lipophilicity as ddI. This indicates that PNP may not
      play an important role in the low intestinal absorption of ddI. The Pblood for 6
      Cl-ddP, (19 +/- 2) x 10(-6) cm/s, was 4.5-fold lower than Plumen, (84 +/- 12) x
      10(-6) cm/s, which means that 77 +/- 6% of 6-Cl-ddP was metabolized during its
      intestinal transport, thus qualitatively accounting for the low oral
      bioavailability (7%) of 6-Cl-ddP observed in vivo in rats. Extensive
      intracellular metabolism of 6-Cl-ddP by ADA was confirmed by the high
      concentrations of ddI found both in the intestinal lumen and blood during 6-Cl
      ddP perfusions and by a rate of ddI appearance in blood which was approximately
      10-fold higher than ddI controls. Co-perfusion of the potent, hydrophilic ADA
      inhibitor DCF (Ki = 0. 001-0.05 nM) with 6-Cl-ddP led to only partial inhibition
      of intestinal ADA, while complete inhibition was obtained using the less potent
      but more lipophilic inhibitor EHNA (Ki = 1-20 nM). Hence, EHNA may be used to
      improve intestinal absorption of 6-Cl-ddP in vivo.

PMID- 9572908
TI  - Optimization of the local inhibition of intestinal adenosine deaminase (ADA) by
      erythro-9-(2-hydroxy-3-nonyl)adenine: enhanced oral delivery of an ADA-activated
      prodrug for anti-HIV therapy.
AB  - Previous in situ perfusion studies in rat ileal segments have demonstrated that
      high concentrations (>40 microg/mL) of erythro-9-(2-hydroxy-3-nonyl)adenine
      (EHNA), a semitight binding inhibitor of adenosine deaminase (ADA), are effective
      in completely inhibiting the intestinal metabolism of 6-chloro-2',3'
      dideoxypurine (6-Cl-ddP), an ADA activated prodrug of the anti-HIV agent 2', 3'
      dideoxyinosine (ddI) designed for improved targeting to the central nervous
      system. However, the intestinal absorption of EHNA results in complete inhibition
      of the ADA activity in the mesenteric blood draining the isolated intestinal
      segment being perfused and may lead to complete inhibition of ADA present in the
      systemic circulation and other sites, an unacceptable outcome since bioconversion
      in the target tissue is required for prodrug efficacy. This study examines the
      feasibility of locally inhibiting ADA present in the intestinal wall using EHNA
      to increase the intestinal absorption of 6-Cl-ddP. Transport experiments
      conducted in isolated ileal segments from mesenteric cannulated rats using
      perfusate containing prodrug and various concentrations of EHNA demonstrated that
      a 0.1 microg/mL logarithmic mean lumenal concentration of EHNA was effective in
      increasing the intestinal bioavailability of Cl-ddP to > 90%. Intestinal uptake
      parameters for EHNA and pharmacokinetic parameters generated in vivo in
      chronically catheterized rats given intravenous infusions ranging from 12.5 to
      310 microg/kg/min were used to demonstrate that <10% of systemic ADA would be
      inhibited at steady state using the optimal perfusate concentration of EHNA.
      Thus, in continuous perfusions it is possible to increase the intestinal
      bioavailability of 6-Cl-ddP to >90% with minimal (<10%) inhibition of systemic
      ADA. Local inhibition of enzymes may be an effective strategy to increase the
      oral bioavailability of tissue enzyme-activated prodrugs or other drugs which may
      also be substrates for intestinal enzymes.

PMID- 9572909
TI  - Effect of interparticulate interaction on release kinetics of microsphere
      ensembles.
AB  - The release kinetics of microsphere ensembles is complicated by the mutual
      influence of the microspheres which are entrapped in small compartments such as
      body cavities. This work focused on the effect of interparticulate interaction on
      the release kinetics of microsphere ensembles with limited spreading. Experiments
      and finite element modeling were conducted to investigate diffusional drug
      release from a single sphere, a monolayer, and multiple layers of microspheres.
      Poly(methyl methacrylate-co-methacrylic acid) (P(MMA/MAA)) microspheres and
      azidothymidine (AZT) were used in the experiments. The order of the release rate
      of AZT from various microsphere populations was observed to be single sphere >
      monolayer > multiple layers. This evidenced the importance of interparticulate
      interaction. The finite element simulations elucidated the influence of various
      factors on the release kinetics of microsphere ensembles including the separation
      distance, location of the spheres, and the drug accumulation in the medium.
      Calibration of overall release kinetics for the neighboring effect was proposed
      on the basis of the spreading factor. Overall release profiles of microsphere
      ensembles were predicted using the release profiles of individual microspheres at
      various locations.

PMID- 9572910
TI  - Pharmacokinetics of aniracetam and its metabolites in rats.
AB  - The pharmacokinetics of aniracetam (AP), a new cognitive performance enhancer,
      and its main metabolites was investigated after intravenous (iv) and oral
      administrations to rat. The plasma levels of AP, 4-p-anisamidobutyric acid (ABA),
      and p-anisic acid (AA) were determined simultaneously by the HPLC method. The
      plasma concentrations of the parent drug and ABA quickly declined in a
      biexponential manner, with rapid terminal decay and a small mean residence time.
      However, AA yielded nonlinearly high levels at the initial times and the plasma
      concentrations of 2-pyrrolidinone (PD) were sustained over a relatively long
      time. When AA was administered intravenously, nonlinearity of the plasma
      concentrations was also found at higher doses. To describe the time course of the
      plasma levels of AP and its metabolites after iv administration, a
      pharmacokinetic model with seven compartments was applied, which included 10
      first-order rate constants and one Michaelis-Menten constant. An approximate fit
      was obtained between the observed and calculated curves based on the model,
      except for the plasma concentrations of ABA. The plasma concentration-time
      profiles of AP and its metabolites following oral administration of AP (50 and
      100 mg/kg) were similar to those after iv dosing, with the exception of PD, which
      showed much lower plasma levels than those after iv administration. Elimination
      of AP and ABA was rapid after oral dosing, and the bioavailability of AP was
      extremely small (11.4 and 8.6%). As a result, AP was largely metabolized to ABA,
      AA, and PD in rat.

PMID- 9572911
TI  - The effect of ionic strength on liposome-buffer and 1-octanol-buffer distribution
      coefficients.
AB  - The distribution of salmeterol and proxicromil between unilamellar vesicles of
      dioleoylphosphatidylcholine (DOPC) and aqueous buffer at pH 7.4 has been studied,
      using an ultrafiltration method, as a function of compound concentration, DOPC
      concentration, and buffer ionic strength. The binding of these ionized lipophilic
      compounds to neutral DOPC vesicles induces a surface charge, which causes the
      observed membrane distribution coefficient D(mem)obs to vary significantly with
      bound compound to DOPC ratio and with ionic strength. This variability is shown
      to be well-described with use of the Gouy-Chapman theory of the ionic double
      layer and is contrasted with the ideal behavior shown by the neutral compound
      clofibrate. Increasing ionic strength is also shown to increase the observed 1
      octanol-buffer distribution coefficients D(o/w)obs of proxicromil but through a
      very different mechanism involving the extraction of ion pairs. This study
      highlights the experimental difficulty in determining concentration-independent
      liposome distribution coefficients of ionized lipophilic compounds and describes
      when deviations will be significant and how observed values may be corrected for
      such effects. The general effect of ionic strength on membrane-buffer
      distribution and 1-octanol-buffer distribution is discussed with particular
      reference to the very different propensity for ion pair formation shown by the
      two systems, and the most suitable experimental conditions that should be used
      with each system.

PMID- 9572912
TI  - Model-independent estimation of lag times with first-order absorption and
      disposition.
AB  - The effectiveness of five model-independent procedures for the estimation of lag
      times (Tlag) was evaluated. Two new methods utilize early concentrations which
      are weighted by a term exponential in time. They estimate Tlag by weighted linear
      regression. One of these approaches evaluates also the time when maximum
      concentration is reached (Tmax). In addition, three older, empirically used
      procedures are considered. Two methods apply either the first two or three
      quantifiable concentrations and estimate the lag time by linear regression.
      Finally, the last unquantifiable concentration is often used as a measure of lag
      time. Simulations demonstrated that this procedure had large bias and generally
      high standard deviation. In contrast, the new methods showed small variation and
      negligible bias. The procedures applying linear regression had intermediate
      characteristics. Lag times were evaluated effectively by an average of two
      observations between Tlag and Tmax.

PMID- 9572913
TI  - Perfusion cells for studying regional variation in oral mucosal permeability in
      humans. 2. A specialized transport mechanism in D-glucose absorption exists in
      dorsum of tongue.
AB  - To clarify the site of d-glucose absorption in human oral cavity, newly designed
      perfusion cells were applied to five different sites in the human oral cavity,
      i.e., the dorsum of the tongue, the ventral surface of the tongue, the labial
      mucosa, the floor of the mouth, and the buccal mucosa. The solution of D-glucose
      was perfused for 1 h and the rate of absorption was calculated from the amount
      that disappeared from the perfusate. D-Glucose was absorbed rapidly from the
      dorsum of the tongue and the absorption was saturable. The saturable absorption
      was also observed in the ventral surface of the tongue, but not in the other
      three sites. The rate of D-glucose absorption in the dorsum and the ventral
      surface of the tongue was significantly larger than that of L-glucose, while in
      the other sites they were not significantly different. The presence of a
      specialized transport system for D-glucose absorption in the dorsum of human
      tongue was suggested.

PMID- 9572914
TI  - Liposomal delivery of a 30-mer antisense oligodeoxynucleotide to inhibit
      proopiomelanocortin expression.
AB  - An oligodeoxynucleic sequence of 30 bases (30-mer ODN), complementary to a region
      of beta-endorphin mRNA, was synthesized to have an antisense effect with regard
      to the expression of this oligopeptide. Following the solid-phase synthesis of
      the oligodeoxynucleotide, the 30-mer ODN was encapsulated within liposomes to
      provide a higher resistance against DNases and an improved entrance into cells.
      The most suitable liposome formulation as a 30-mer ODN carrier consisted of small
      unilamellar vesicles (50 nm) with an encapsulation capacity of 4.76
      microL/micromol. The liposomal formulations containing dipalmitoyl-DL-alpha
      phosphatidyl-L-serine presented fusogenic properties, which are of great
      importance for the delivery of antisense compounds. The antisense activity of 30
      mer ODN-loaded liposomes was evaluated by the determination of beta-endorphin
      levels in AtT-20 cells. The free 30-mer ODN did not provide any lowering of the
      beta-endorphin production, whereas the liposomally entrapped compound elicited a
      concentration-dependent inhibition. The inhibition was determined by a sequence
      specific binding of the 30-mer ODN with the target mRNA.

PMID- 9572915
TI  - Species differences in size discrimination in the paracellular pathway reflected
      by oral bioavailability of poly(ethylene glycol) and D-peptides.
AB  - Animal models are frequently used to aid prediction of intestinal absorption in
      humans. However, there is little comparative quantitative information on species
      differences in paracellular permeation, which is an important route for oral
      absorption of small to medium-sized hydrophilic drug molecules. This study
      addresses this issue by comparing the molecular mass (MM) dependency in oral
      bioavailability between rat and dog of poly(ethylene glycol) (PEG), a
      polydispersed model mixture commonly used to characterize paracellular
      absorption, and of a series of eight D-peptides (based on D-phenylalanine).
      Fasted rats and dogs received PEG (400/900) and the D-peptides (MM 236-406 Da),
      orally and intravenously, with total 24-48 h urine collection to estimate oral
      bioavailability. After HPLC separation, the individual PEG oligomers and D
      peptides were determined using radiometric detection, for radiolabeled material,
      and LC-MS, for unlabeled (PEG) material. All compounds were predominantly
      excreted unchanged following intravenous administration. After oral
      administration, the predominant peak in the radiochromatogram was unchanged
      material, indicating stability of the compounds in the gastrointestinal tract. A
      clear molecular mass dependency in oral bioavailability was seen with both
      series, but with absorption much greater in dog than rat. Thus, for PEG in rat,
      bioavailability decreased sharply from 79 to around 2% with increasing MM between
      282 and 591 Da, and then tapered to around 1. 5% up to 1295 Da. Whereas in dog,
      bioavailability remained around 100% for oligomers up to 600 Da and then
      decreased quite sharply with increasing MM, tending to plateau around 13% beyond
      900 Da. Likewise, for the d-peptides in rat, bioavailability decreased from 30 to
      1% with increasing MM between 236 and 406 Da, whereas in dog it was 100%,
      declining to 16% over the same molecular range. This species difference appears
      to be due to a larger pore size and greater frequency of pores in the
      paracellular pathway of dog compared to rat. Furthermore, on the basis of
      comparison with literature data for PEG and selected drugs, rat would appear to
      be a better predictor than dog of absorption of hydrophilic compounds in human.

PMID- 9572916
TI  - What surface of the intestinal epithelium is effectively available to permeating
      drugs?
AB  - A mathematical model is presented which examines the extent to which the
      intestinal epithelium is accessed by drug molecules. Morphological information
      from the literature for the jejunum, ileum, and colon of the rat and for human
      jejunum was incorporated. Perturbation theory was used to derive the limiting
      cases for total access to the entire epithelial surface, for transport by
      diffusion and by diffusion with convection, respectively. A parameter gamma =
      square root of (Ph2)/(Db) was identified to provide a measure of the ability of
      drug molecules to access the entire epithelial surface down to the crypt wells,
      where P is the cell permeability, D the aqueous diffusion coefficient, h the
      channel depth between the villi, and b is half the width of the idealized
      intervillous channel. When gamma << 1, diffusion is not a limitation and the
      entire surface is fully utilized for absorption of drug. This condition arises
      with drugs of low permeability and is more likely to be met with colonic than
      small intestinal epithelium. When gamma >/= 1, diffusion becomes a limitation and
      then not all of the epithelial surface is functionally accessible to drug
      molecules, a condition most likely to prevail with drugs of high permeability
      traversing the jejunum. Furthermore, water flux per se is predicted to have
      relatively little influence on enhancing surface accessibility. This simple, but
      quantitative approach showed that the ranking order of permeability jejunum
      >ileum> colon for low permeable drugs can at least in part be explained by the
      differences in surface amplification between these different epithelial regions.
      The analysis also indicates that for highly permeable drugs extreme caution
      should be exercised in extrapolating permeability measurements in vitro across
      various preparations and to events in vivo.

PMID- 9572917
TI  - Spontaneous chemiluminescence production, lipid peroxidation, and covalent
      binding in rat hepatocytes exposed to acetaminophen.
AB  - Spontaneous chemiluminescence associated with the cell injury was observed in the
      isolated rat hepatocyte suspension during acetaminophen (APAP) metabolism,
      indicating the occurrence of oxidative stress. APAP apparently affected the
      hepatocytes in various manners. APAP, at low concentrations (1-2 mM), damaged the
      hepatocytes due to lipid peroxidation provoked during APAP metabolism, while at
      high concentrations (5-50 mM), APAP protected the hepatocytes due to a chemical
      antioxidant effect of the unmetabolized APAP that remained in the medium because
      of the saturation of APAP metabolism. The covalent binding of APAP to the
      hepatocytes increased with APAP concentration up to 50 mM without loss of cell
      viability. When an overdose of APAP was administered to rats, the APAP plasma
      concentration was around 1-3 mM, which corresponded to the concentration range
      where lipid peroxidation occurred in the isolated hepatocytes. Thus, it seems
      likely that lipid peroxidation contributes to the APAP-induced hepatotoxicity in
      the early stage of the toxic process.

PMID- 9572918
TI  - Solid state characterization of spray-dried powders of recombinant human
      deoxyribonuclease (rhDNase).
AB  - rhDNase is a recombinant human protein approved as an aqueous solution for human
      use by inhalation. To study the feasibility of preparation of dry powders for
      inhalation, spray-dried powders of pure rhDNase and co-spray-dried mixtures of
      rhDNase with an excipient approved for inhalation products, lactose, were
      prepared. Both types of powders were initially amorphous. The lactose, however,
      was found to crystallize after exposure to a humid environment. The crystals in
      the powder were identified as the alpha-monohydrate polymorph of lactose by hot
      stage optical and scanning electron microscopy, differential scanning calorimetry
      and thermogravimetry, FTIR spectroscopy, and X-ray powder diffraction. Moisture
      sorption isotherms indicated that crystallization occurred at high relative
      humidities (70-85%), depending on the temperature of the environment (5-40
      degreesC). The practical implications for the manufacturing and storage of
      protein powders for inhalation are discussed.

PMID- 9572919
TI  - Solid-state characterization of chlordiazepoxide polymorphs.
AB  - A novel crystal form (form II) of the benzodiazepine chlordiazepoxide is
      reported. The new polymorphic phase was characterized and distinguished from the
      standard form (form I) by X-ray diffractometry, differential scanning
      calorimetry, infrared spectroscopy, microscopy, solution calorimetry, and solid
      state nuclear magnetic resonance. The formation of form II was dependent on the
      crystallizing solvent, being the predominant form isolated from methanol.
      Recrystallization from other alcoholic solutions (ethanol, propanol, and butanol)
      and toluene yielded form I. Differential scanning calorimetry and powder X-ray
      diffraction indicated that the two forms were enantiotropically related with a
      transition of form II to form I occurring between 200 and 225 degreesC. Visual
      examination by hot stage microscopy in this temperature range revealed a dramatic
      solid-state transition. Single-crystal X-ray analysis was performed on form II
      which was found to crystallize in the triclinic space group P1 with a = 10.736(2)
      A, b = 16.921(4) A, c = 17.041(4) A, alpha = 100.76(1) degrees, beta = 95.27(1)
      degrees, gamma = 97.53(1) degrees, Z = 8, and dcal = 1.33 g/cm3. When compared
      with the published crystal structure of form I, the cell symmetry, volume, and
      density were similar. Both structures consisted of four crystallographically
      independent molecules linked in pairs through intermolecular hydrogen bonding.
      Differences were observed in the packing arrangement of the dimers in the
      polymorphs. The small heat of transition calculated from solution calorimetry
      (1.5 kJ mol-1) was sufficient to effect a crystallographic rearrangement of the
      dimers.

PMID- 9572920
TI  - Meropenem exists in equilibrium with a carbon dioxide adduct in bicarbonate
      solution.
AB  - Evidence is provided for the existence of a second discrete chemical form of
      meropenem at clinically relevant concentrations prepared from the marketed
      formulation of the drug. Proton and carbon-13 NMR spectra in D2O, coupled with
      tandem mass spectroscopy (MS/MS) and cross polarization/magic angle spinning (CP
      MAS) NMR experiments, allow structural assignment of the compound as a covalent
      carbon dioxide adduct of meropenem. This carbon dioxide adduct exists in
      equilibrium with the free drug in solution and can be observed in the solid state
      following lyophilization. The equilibrium constant of formation of the adduct
      (Keq = 20 +/- 8 M-1) was estimated in D2O at 25 degreesC.

PMID- 9572921
TI  - High-fidelity translation of recombinant human hemoglobin in Escherichia coli.
AB  - Coexpression of di-alpha-globin and beta-globin in Escherichia coli in the
      presence of exogenous heme yielded high levels of soluble, functional recombinant
      human hemoglobin (rHb1.1). High-level expression of rHb1.1 provides a good model
      for measuring mistranslation in heterologous proteins. rHb1.1 does not contain
      isoleucine; therefore, any isoleucine present could be attributed to
      mistranslation, most likely mistranslation of one or more of the 200 codons that
      differ from an isoleucine codon by 1 bp. Sensitive amino acid analysis of highly
      purified rHb1.1 typically revealed < or = 0.2 mol of isoleucine per mol of
      hemoglobin. This corresponds to a translation error rate of < or = 0.001, which
      is not different from typical translation error rates found for E. coli proteins.
      Two different expression systems that resulted in accumulation of globin proteins
      to levels equivalent to approximately 20% of the level of E. coli soluble
      proteins also resulted in equivalent translational fidelity.

PMID- 9572922
TI  - Mechanism of the citrate transporters in carbohydrate and citrate cometabolism in
      Lactococcus and Leuconostoc species.
AB  - Citrate metabolism in the lactic acid bacterium Leuconostoc mesenteroides
      generates an electrochemical proton gradient across the membrane by a secondary
      mechanism (C. Marty-Teysset, C. Posthuma, J. S. Lolkema, P. Schmitt, C. Divies,
      and W. N. Konings, J. Bacteriol. 178:2178-2185, 1996). Reports on the energetics
      of citrate metabolism in the related organism Lactococcus lactis are
      contradictory, and this study was performed to clarify this issue. Cloning of the
      membrane potential-generating citrate transporter (CitP) of Leuconostoc
      mesenteroides revealed an amino acid sequence that is almost identical to the
      known sequence of the CitP of Lactococcus lactis. The cloned gene was expressed
      in a Lactococcus lactis Cit- strain, and the gene product was functionally
      characterized in membrane vesicles. Uptake of citrate was counteracted by the
      membrane potential, and the transporter efficiently catalyzed heterologous
      citrate-lactate exchange. These properties are essential for generation of a
      membrane potential under physiological conditions and show that the Leuconostoc
      CitP retains its properties when it is embedded in the cytoplasmic membrane of
      Lactococcus lactis. Furthermore, using the same criteria and experimental
      approach, we demonstrated that the endogenous CitP of Lactococcus lactis has the
      same properties, showing that the few differences in the amino acid sequences of
      the CitPs of members of the two genera do not result in different catalytic
      mechanisms. The results strongly suggest that the energetics of citrate
      degradation in Lactococcus lactis and Leuconostoc mesenteroides are the same;
      i.e., citrate metabolism in Lactococcus lactis is a proton motive force
      generating process.

PMID- 9572923
TI  - Characterization of laccases and peroxidases from wood-rotting fungi (family
      Coprinaceae).
AB  - Panaeolus sphinctrinus, Panaeolus papilionaceus, and Coprinus friesii are
      described as producers of ligninolytic enzymes. P. papilionaceus and P.
      sphinctrinus both produced a laccase. In addition, P. sphinctrinus produced a
      manganese peroxidase. C. friesii secreted a laccase and two peroxidases similar
      to the peroxidase of Coprinus cinereus. The purified laccases and peroxidases
      were characterized by broad substrate specificities, significant enzyme
      activities at alkaline pH values, and remarkably high pH optima. The two
      peroxidases of C. friesii remained active at pH 7.0 and 60 degrees C for up to 60
      min of incubation. The peroxidases were inhibited by sodium azide and ethylene
      glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), whereas the
      laccases were inhibited by sodium azide and N,N-diethyldithiocarbamic acid. As
      determined by native polyacrylamide gel electrophoresis and isoelectric focusing,
      all three fungi produced laccase isoenzymes.

PMID- 9572924
TI  - Overproduction of L-cysteine and L-cystine by Escherichia coli strains with a
      genetically altered serine acetyltransferase.
AB  - Organisms that overproduced L-cysteine and L-cystine from glucose were
      constructed by using Escherichia coli K-12 strains. cysE genes coding for altered
      serine acetyltransferase, which was genetically desensitized to feedback
      inhibition by L-cysteine, were constructed by replacing the methionine residue at
      position 256 of the serine acetyltransferase protein with 19 other amino acid
      residues or the termination codon to truncate the carboxy terminus from amino
      acid residues 256 to 273 through site-directed mutagenesis by using PCR. A
      cysteine auxotroph, strain JM39, was transformed with plasmids having these
      altered cysE genes. The serine acetyltransferase activities of most of the
      transformants, which were selected based on restored cysteine requirements and
      ampicillin resistance, were less sensitive than the serine acetyltransferase
      activity of the wild type to feedback inhibition by L-cysteine. At the same time,
      these transformants produced approximately 200 mg of L-cysteine plus L-cystine
      per liter, whereas these amino acids were not detected in the recombinant strain
      carrying the wild-type serine acetytransferase gene. However, the production of L
      cysteine and L-cystine by the transformants was very unstable, presumably due to
      a cysteine-degrading enzyme of the host, such as cysteine desulfhydrase.
      Therefore, mutants that did not utilize cysteine were derived from host strain
      JM39 by mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. When a newly
      derived host was transformed with plasmids having the altered cysE genes, we
      found that the production of L-cysteine plus L-cystine was markedly increased
      compared to production in JM39.

PMID- 9572925
TI  - A gene system for glucitol transport and metabolism in Clostridium beijerinckii
      NCIMB 8052.
AB  - The gutD gene of Clostridium beijerinckii NCIMB 8052 encoding glucitol 6
      phosphate dehydrogenase was cloned on a 5.7-kbp chromosomal DNA fragment by
      complementing an Escherichia coli gutD mutant strain and selecting for growth on
      glucitol. Five open reading frames (ORFs) in the order gutA1 gutA2 orfX gutB gutD
      were identified in a 4.0-kbp region of the cloned DNA. The deduced products of
      four of these ORFs were homologous to components of the glucitol
      phosphotransferase system (PTS) and glucitol 6-phosphate dehydrogenase from E.
      coli, while the remaining ORF (orfX) encoded an enzyme which had similarities to
      members of a family of transaldolases. A strain in which gutD was inactivated by
      targeted integration lacked glucitol 6-phosphate dehydrogenase activity. The
      gutA1 and gutA2 genes encoded two polypeptides forming enzyme IIBC of the
      glucitol PTS comprising three domains in the order CBC. Domain IIA of the
      glucitol PTS was encoded by gutB. Glucitol phosphorylation assays in which
      soluble and membrane fractions of cells grown on glucose (which did not
      synthesize the glucitol PTS) or cells grown on glucitol were used confirmed that
      there is a separate, soluble, glucitol-specific PTS component, which is the
      product of the gutB gene. The gut genes were regulated at the level of
      transcription and were induced in the presence of glucitol. Cells grown in the
      presence of glucose and glucitol utilized glucose preferentially. Following
      depletion of glucose, the glucitol PTS and glucitol 6-phosphate dehydrogenase
      were synthesized, and glucitol was removed from the culture medium. RNA analysis
      showed that the gut genes were not expressed until glucose was depleted.

PMID- 9572926
TI  - High levels of endemicity of 3-chlorobenzoate-degrading soil bacteria.
AB  - Soils samples were obtained from pristine ecosystems in six regions on five
      continents. Two of the regions were boreal forests, and the other four were
      Mediterranean ecosystems. Twenty-four soil samples from each of four or five
      sites in each of the regions were enriched by using 3-chlorobenzoate (3CBA), and
      3CBA mineralizers were isolated from most samples. These isolates were analyzed
      for the ability to mineralize 3CBA, and genotypes were determined with repetitive
      extragenic palindromic PCR genomic fingerprints and restriction digests of the
      16S rRNA genes (amplified ribosomal DNA restriction analysis [ARDRA]). We found
      that our collection of 150 stable 3CBA-mineralizing isolates included 48
      genotypes and 44 ARDRA types, which formed seven distinct clusters. The majority
      (91%) of the genotypes were unique to the sites from which they were isolated,
      and each genotype was found only in the region from which it was isolated. A
      total of 43 of the 44 ARDRA types were found in only one region. A few genotypes
      were repeatedly found in one region but not in any other continental region,
      suggesting that they are regionally endemic. A correlation between bacterial
      genotype and vegetative community was found for the South African samples. These
      results suggest that the ability to mineralize 3CBA is distributed among very
      diverse genotypes and that the genotypes are not globally dispersed.

PMID- 9572927
TI  - Heterobinary adhesins based on the Escherichia coli FimH fimbrial protein.
AB  - The FimH adhesin of Escherichia coli type 1 fimbriae confers the ability to bind
      to D-mannosides by virtue of a receptor-binding domain located in its N-terminal
      region. This protein was engineered into a heterobifunctional adhesin by
      introducing a secondary binding site in the C-terminal region. The insertion of
      histidine clusters into this site resulted in coordination of various metal ions
      by recombinant cells expressing chimeric FimH proteins. In addition, libraries
      consisting of random peptide sequences inserted into the FimH display system and
      screened by a "panning" technique were used to identify specific sequences
      conferring the ability to adhere to Ni2+ and Cu2+. Recombinant cells expressing
      heterobifunctional FimH adhesins could adhere simultaneously to both metals and
      saccharides. Finally, combining the metal-binding modifications with alterations
      in the natural receptor-binding region demonstrated the ability to independently
      modulate the binding of FimH to two ligands simultaneously.

PMID- 9572928
TI  - A rapid PCR-based DNA test for enterotoxic Bacillus cereus.
AB  - The occurrence of DNA sequences encoding the hemolysin HblA complex and Bacillus
      cereus enterotoxin BceT, which have recently been confirmed as enterotoxins, was
      studied in Bacillus spp. To amplify these DNA sequences, PCR primer systems for
      the B component of hblA and for bceT DNA sequences were developed. The results
      from the amplification of hblA sequences correlated well with results obtained
      with the B. cereus enterotoxin (diarrheal type) test kit (RPLA kit), but not with
      the results of the Bacillus diarrheal enterotoxin visual immunoassay (BDE kit).
      Except for two thermophilic strains, all strains that were positive in PCR
      amplification assays with the hblA primers were also positive when tested with
      the RPLA kit. The hblA DNA sequence was found in 33 strains, and these strains
      were closely related according to 16S rDNA-RFLP analysis, except B. pasteurii. In
      PCR amplifications with the bceT primers only the model strain gave a positive
      signal. It is concluded that screening of the hemolysin HblA complex by the PCR
      method allows faster detection of enterotoxin production than does testing with
      the RPLA enterotoxin kit.

PMID- 9572929
TI  - Influence of cold stress on the preliminary enrichment time needed for detection
      of enterohemorrhagic Escherichia coli in ground beef by PCR.
AB  - The influence of cold stress at 4 and 0 degree C on the detection time as
      assessed by impedance technology (Bactometer; Biomerieux, Marcy l'Etoile, France)
      of different enterohemorrhagic Escherichia coli (EHEC) strains was determined.
      Although there is some variation in susceptibility among EHEC strains, prolonged
      exposure of EHEC to cold stress, i.e., 4 and 5 days at 4 and 0 degree C,
      respectively, in general significantly increased their detection time. This
      reflects an increase of the lag-phase time caused by cold stress. Two EHEC
      strains were selected to determine the minimum preliminary enrichment time that
      would ensure a positive PCR detection of low numbers of verotoxin-producing E.
      coli (VTEC; 2 to 2 x 10(5) CFU/25 g) inoculated into ground beef (25 g) and
      stored at 4 or -20 degrees C for 8 and 14 days, respectively. Incubation times of
      6 and 9 h of 1 to 10 CFU/g and 1 to 10 CFU/25 g, respectively, were sufficient
      for PCR detection of VTEC in ground beef when analysis was performed immediately
      after inoculation (no cold stress). When cells are exposed to cold stress (4 or 
      20 degrees C) a 24-h enrichment period is recommended. Restriction of enrichment
      time to 9 h under these circumstances decreases the sensitivity of PCR detection
      to 80 CFU/g. Hence, to obtain maximum sensitivity, PCR detection of VTEC in
      naturally contaminated ground beef should be performed after 24 h of enrichment.

PMID- 9572930
TI  - Effect of Leuconostoc mesenteroides NRRL B-512F dextransucrase carboxy-terminal
      deletions on dextran and oligosaccharide synthesis.
AB  - Dextransucrase (DSR-S) from Leuconostoc mesenteroides NRRL B-512F is a
      glucosyltransferase that catalyzes synthesis of soluble dextran from sucrose. In
      the presence of efficient acceptor molecules, such as maltose, the reaction
      pathway is shifted toward glucooligosaccharide synthesis. Like
      glucosyltransferases from oral streptococci, DSR-S possesses a C-terminal glucan
      binding domain composed of a series of tandem repeats. In order to determine the
      role of the C-terminal region of DSR-S in dextran or oligosaccharide synthesis,
      four DSR-S genes with deletions at the 3' end were constructed. The results
      showed that the C-terminal region modulated the initial velocity of dextran
      synthesis but that the K(m) for sucrose, the optimum pH, and the activation
      energy were all unaffected by the deletions. The C-terminal domain modulated the
      rate of oligosaccharide synthesis whatever acceptor molecule was used (a good
      acceptor molecule such as maltose or a poor acceptor molecule such as fructose).
      The C-terminal domain seemed to play no role in the catalytic process in dextran
      and oligosaccharide synthesis. In fact, it seems that the role of the C-terminal
      domain of DSR-S may be to facilitate the translation of dextran and
      oligosaccharides from the catalytic site.

PMID- 9572931
TI  - Identification and analysis of genes involved in anaerobic toluene metabolism by
      strain T1: putative role of a glycine free radical.
AB  - The denitrifying strain T1 is able to grow with toluene serving as its sole
      carbon source. Two mutants which have defects in this toluene utilization pathway
      have been characterized. A clone has been isolated, and subclones which contain
      tutD and tutE, two genes in the T1 toluene metabolic pathway, have been
      generated. The tutD gene codes for an 864-amino-acid protein with a calculated
      molecular mass of 97,600 Da. The tutE gene codes for a 375-amino-acid protein
      with a calculated molecular mass of 41,300 Da. Two additional small open reading
      frames have been identified, but their role is not known. The TutE protein has
      homology to pyruvate formate-lyase activating enzymes. The TutD protein has
      homology to pyruvate formate-lyase enzymes, including a conserved cysteine
      residue at the active site and a conserved glycine residue that is activated to a
      free radical in this enzyme. Site-directed mutagenesis of these two conserved
      amino acids shows that they are also essential for the function of TutD.

PMID- 9572932
TI  - A transposable partitioning locus used to stabilize plasmid-borne hydrogen
      oxidation and trifolitoxin production genes in a Sinorhizobium strain.
AB  - Improved nitrogen-fixing inoculum strains for leguminous crops must be able to
      effectively compete with indigenous strains for nodulation, enhance legume
      productivity compared to the productivity obtained with indigenous strains, and
      maintain stable expression of any added genes in the absence of selection
      pressure. We constructed a transposable element containing the tfx region for
      expression of increased nodulation competitiveness and the par locus for plasmid
      stability. The transposon was inserted into tetA of pHU52, a broad-host-range
      plasmid conferring the H2 uptake phenotype. The resulting plasmid, pHUTFXPAR,
      conferred the plasmid stability, trifolitoxin production, and H2 uptake
      phenotypes in the broad-host-range organism Sinorhizobium sp. strain ANU280. The
      broad applications of a transposon conferring plasmid stability are discussed.

PMID- 9572933
TI  - Distribution of Xanthomonas oryzae pv. oryzae DNA modification systems in Asia.
AB  - The presence or absence of two DNA modification systems, XorI and XorII, in 195
      strains of Xanthomonas oryzae pv. oryzae collected from different major rice
      growing countries of Asia was assessed. All four possible phenotypes (XorI+
      XorII+, XorI+ XorII-, XorI- XorII+ and XorI- XorII-) were detected in the
      population at a ratio of approximately 1:2:2:2. The XorI+ XorII+ and XorI- XorII+
      phenotypes were observed predominantly in strains from southeast Asia
      (Philippines, Malaysia, and Indonesia), whereas strains with the phenotypes XorI-
      XorII- and XorI+ XorII- were distributed in south Asia (India and Nepal) and
      northeast Asia (China, Korea, and Japan), respectively. Based on the prevalence
      and geographic distribution of the XorI and XorII systems, we suggest that the
      XorI modification system originated in northeast Asia and was later introduced to
      southeast Asia, while the XorII system originated in southeast Asia and moved to
      northeast Asia and south Asia. Genomic DNA from all tested strains of X. oryzae
      pv. oryzae that were resistant to digestion by endonuclease XorII or its
      isoschizomer PvuI also hybridized with a 7.0-kb clone that contained the XorII
      modification system, whereas strains that were digested by XorII or PvuI lacked
      DNA that hybridized with the clone. Size polymorphisms were observed in fragments
      that hybridized with the 7.0-kb clone. However, a single hybridization pattern
      generally was found in XorII+ strains within a country, indicating clonal
      maintenance of the XorII methyl-transferase gene locus. The locus was monomorphic
      for X. oryzae pv. oryzae strains from the Philippines and all strains from
      Indonesia and Korea.

PMID- 9572934
TI  - A flow cytometric method for rapid selection of novel industrial yeast hybrids.
AB  - We rapidly produced and isolated novel yeast hybrids by using two-color flow
      cytometric cell sorting. We labeled one parent strain with a fluorescent green
      stain and the other parent with a fluorescent orange stain, and hybrids were
      selected based on their dual orange and green fluorescence. When this technique
      was applied to the production of hybrids by traditional mating procedures, more
      than 96% of the isolates were hybrids. When it was applied to rare mating, three
      hybrids were identified among 50 isolates enriched from a population containing 2
      x 10(6) cells. This technology is not dependent on genetic markers and has
      applications in the development of improved industrial yeast strains.

PMID- 9572935
TI  - A deficiency in aspartate biosynthesis in Lactococcus lactis subsp. lactis C2
      causes slow milk coagulation.
AB  - A mutant of fast milk-coagulating (Fmc+) Lactococcus lactis subsp. lactis C2,
      designated L. lactis KB4, was identified. Although possessing the known
      components essential for utilizing casein as a nitrogen source, which include
      functional proteinase (PrtP) activity and oligopeptide, di- and tripeptide, and
      amino acid transport systems, KB4 exhibited a slow milk coagulation (Fmc-)
      phenotype. When the amino acid requirements of L. lactis C2 were compared with
      those of KB4 by use of a chemically defined medium, it was found that KB4 was
      unable to grow in the absence of aspartic acid. This aspartic acid requirement
      could also be met by aspartate-containing peptides. The addition of aspartic acid
      to milk restored the Fmc+ phenotype of KB4. KB4 was found to be defective in
      pyruvate carboxylase and thus was deficient in the ability to form oxaloacetate
      and hence aspartic acid from pyruvate and carbon dioxide. The results suggest
      that when lactococci are propagated in milk, aspartate derived from casein is
      unable to meet fully the nutritional demands of the lactococci, and they become
      dependent upon aspartate biosynthesis.

PMID- 9572936
TI  - Phylogenetic evidence for the existence of novel thermophilic bacteria in hot
      spring sulfur-turf microbial mats in Japan.
AB  - So-called sulfur-turf microbial mats, which are macroscopic white filaments or
      bundles consisting of large sausage-shaped bacteria and elemental sulfur
      particles, occur in sulfide-containing hot springs in Japan. However, no
      thermophiles from sulfur-turf mats have yet been isolated as cultivable strains.
      This study was undertaken to determine the phylogenetic positions of the sausage
      shaped bacteria in sulfur-turf mats by direct cloning and sequencing of 16S rRNA
      genes amplified from the bulk DNAs of the mats. Common clones with 16S rDNA
      sequences with similarity levels of 94.8 to 99% were isolated from sulfur-turf
      mat samples from two geographically remote hot springs. Phylogenetic analysis
      showed that the phylotypes of the common clones formed a major cluster with
      members of the Aquifex-Hydrogenobacter complex, which represents the most deeply
      branching lineage of the domain bacteria. Furthermore, the bacteria of the sulfur
      turf mat phylotypes formed a clade distinguishable from that of other members of
      the Aquifex-Hydrogenobacter complex at the order or subclass level. In situ
      hybridization with clone-specific probes for 16S rRNA revealed that the common
      phylotype of sulfur-turf mat bacteria is that of the predominant sausage-shaped
      bacteria.

PMID- 9572937
TI  - Isolation of an amoeba naturally harboring a distinctive Legionella species.
AB  - There are numerous in vitro studies documenting the multiplication of Legionella
      species in free-living amoebae and other protozoa. It is believed that protozoa
      serve as host cells for the intracellular replication of certain Legionella
      species in a variety of environmental settings. This study describes the
      isolation and characterization of a bacterium initially observed within an amoeba
      taken from a soil sample. In the laboratory, the bacterium multiplied within and
      was highly pathogenic for Acanthamoeba polyphaga. Extracellular multiplication
      was observed on buffered charcoal yeast extract agar but not on a variety of
      conventional laboratory media. A 16S rRNA gene analysis placed the bacterium
      within the genus Legionella. Serological studies indicate that it is distinct
      from previously described species of the genus. This report also describes
      methods that should prove useful for the isolation and characterization of
      additional Legionella-like bacteria from free-living amoebae. In addition, the
      characterization of bacterial pathogens of amoebae has significant implications
      for understanding the ecology and identification of other unrecognized bacterial
      pathogens.

PMID- 9572938
TI  - Chaperone coexpression plasmids: differential and synergistic roles of DnaK-DnaJ
      GrpE and GroEL-GroES in assisting folding of an allergen of Japanese cedar
      pollen, Cryj2, in Escherichia coli.
AB  - Plasmids that can be used for controlled expression of the DnaK-DnaJ-GrpE and/or
      GroEL-GroES chaperone team were constructed in order to facilitate assessment of
      the effects of these chaperone teams on folding or assembly or recombinant
      proteins in Escherichia coli. A typical pACYC184-based plasmid which was obtained
      could express the major DnaK-DnaJ-GrpE and GroEL-GroES chaperone teams from
      separate promoters when L-arabinose and tetracycline, respectively, were added in
      a dose-dependent fashion. The model protein used to determine whether this system
      was useful was an allergen of Japanese cedar pollen, Cryj2, which was unstable
      when it was produced in E. coli K-12. The effects of chaperone coexpression on
      the folding, aggregation, and stability of Cryj2 were examined in the wild type
      and in several mutant bacteria. Coexpression of the DnaK-DnaJ-GrpE and/or GroEL
      GroES chaperone team at appropriate levels resulted in marked stabilization and
      accumulation of Cryj2 without extensive aggregation. Experiments performed with
      mutants that lack each of the chaperone proteins (DnaK, DnaJ, GrpE, GroEL, and
      GroES) or heat shock transcription factor sigma 32 revealed that both chaperone
      teams are critically involved in Cryj2 folding but that they are involved in
      distinct ways. In addition, it was observed that the two chaperone teams have
      synergistic roles in preventing aggregation of Cryj2 in the absence of sigma 32
      at certain temperatures.

PMID- 9572939
TI  - Improved Most-Probable-Number Method To Detect Sulfate-Reducing Bacteria with
      Natural Media and a Radiotracer
AB  - A greatly improved most-probable-number (MPN) method for selective enumeration of
      sulfate-reducing bacteria (SRB) is described. The method is based on the use of
      natural media and radiolabeled sulfate (35SO42-). The natural media used
      consisted of anaerobically prepared sterilized sludge or sediment slurries
      obtained from sampling sites. The densities of SRB in sediment samples from
      Kysing Fjord (Denmark) and activated sludge were determined by using a normal MPN
      (N-MPN) method with synthetic cultivation media and a tracer MPN (T-MPN) method
      with natural media. The T-MPN method with natural media always yielded
      significantly higher (100- to 1,000-fold-higher) MPN values than the N-MPN method
      with synthetic media. The recovery of SRB from environmental samples was
      investigated by simultaneously measuring sulfate reduction rates (by a 35S
      radiotracer method) and bacterial counts by using the T-MPN and N-MPN methods,
      respectively. When bacterial numbers estimated by the T-MPN method with natural
      media were used, specific sulfate reduction rates (qSO42-) of 10(-14) to 10(-13)
      mol of SO42- cell-1 day-1 were calculated, which is within the range of qSO42-
      values previously reported for pure cultures of SRB (10(-15) to 10(-14) mol of
      SO42- cell-1 day-1). qSO42- values calculated from N-MPN values obtained with
      synthetic media were several orders of magnitude higher (2 x 10(-10) to 7 x 10(
      10) mol of SO42- cell-1 day-1), showing that viable counts of SRB were seriously
      underestimated when standard enumeration media were used. Our results demonstrate
      that the use of natural media results in significant improvements in estimates of
      the true numbers of SRB in environmental samples.

PMID- 9572940
TI  - Starvation-Induced Changes in Motility, Chemotaxis, and Flagellation of Rhizobium
      meliloti
AB  - The changes in motility, chemotactic responsiveness, and flagellation of
      Rhizobium meliloti RMB7201, L5-30, and JJ1c10 were analyzed after transfer of the
      bacteria to buffer with no available C, N, or phosphate. Cells of these three
      strains remained viable for weeks after transfer to starvation buffer (SB) but
      lost all motility within just 8 to 72 h after transfer to SB. The rates of
      motility loss differed by severalfold among the strains. Each strain showed a
      transient, two- to sixfold increase in chemotactic responsiveness toward
      glutamine within a few hours after transfer to SB, even though motility dropped
      substantially during the same period. Strains L5-30 and JJ1c10 also showed
      increased responsiveness to the nonmetabolizable chemoattractant cycloleucine.
      Cycloleucine partially restored the motility of starving cells when added after
      transfer and prevented the loss of motility when included in the SB used for
      initial suspension of the cells. Thus, interactions between chemoattractants and
      their receptors appear to affect the regulation of motility in response to
      starvation independently of nutrient or energy source availability. Electron
      microscopic observations revealed that R. meliloti cells lost flagella and
      flagellar integrity during starvation, but not as fast, nor to such a great
      extent, as the cells lost motility. Even after prolonged starvation, when none of
      the cells were actively motile, about one-third to one-half of the initially
      flagellated cells retained some flagella. Inactivation of flagellar motors
      therefore appears to be a rapid and important response of R. meliloti to
      starvation conditions. Flagellar-motor inactivation was at least partially
      reversible by addition of either cycloleucine or glucose. During starvation, some
      cells appeared to retain normal flagellation, normal motor activity, or both for
      relatively long periods while other cells rapidly lost flagella, motor activity,
      or both, indicating that starvation-induced regulation of motility may proceed
      differently in various cell subpopulations.

PMID- 9572941
TI  - Two new Mycobacterium strains and their role in toluene degradation in a
      contaminated stream.
AB  - Two toluene-degrading strains, T103 and T104, were isolated from rock surface
      biomass in a freshwater stream contaminated with toluene. The strains exhibit
      different capacities for degradation of toluene and other aromatic compounds and
      have characteristics of the genus Mycobacterium. Both are aerobic, rod-shaped,
      gram-positive, nonmotile, and acid-alcohol fast and produce yellow pigments. They
      have mainly straight-chain saturated and monounsaturated fatty acids with 10 to
      20 carbon atoms and large amounts of tuberculostearic acid that are typical of
      mycobacteria. Fatty acid analyses indicate that T103 and T104 are different
      mycobacterial strains that are related at the subspecies level. Their identical
      16S rDNA sequences are most similar to Mycobacterium aurum and Mycobacterium
      komossense, and they constitute a new species of fast-growing mycobacteria.
      Ecological studies reveal that toluene contamination has enriched for toluene
      degrading bacteria in the epilithic microbial community. Strains T103 and T104
      play only a small role in toluene degradation in the stream, although they are
      present in the habitat and can degrade toluene. Other microorganisms are
      consequently implicated in the biodegradation.

PMID- 9572942
TI  - Improved isolation of Vibrio vulnificus from seawater and sediment with
      cellobiose-colistin agar.
AB  - An improved selective medium, cellobiose-colistin (CC) agar, gave a significantly
      higher (P < 0.05) isolation rate of Vibrio vulnificus from water and sediment
      samples than did modified cellobiose-polymyxin B-colistin (mCPC) agar. In a total
      of 446 alkaline peptone water preenrichments amended with polymyxin B, V.
      vulnificus was isolated from 154 preenrichments (35%) with mCPC agar and from 179
      preenrichments (40%) with CC agar. CC agar gave a higher plating efficiency of V.
      vulnificus cells than did cellobiose-polymyxin B-colistin (CPC) agar, mCPC agar,
      or thiosulfate-citrate-bile salts-sucrose (TCBS) agar; the only significant
      difference was observed with TCBS agar, which gave much lower plating
      efficiencies than the other selective media. Determination of MICs demonstrated
      that the concentrations of colistin and polymyxin B in CPC agar inhibit growth of
      a proportion of V. vulnificus strains.

PMID- 9572943
TI  - Comparison of blue nucleic acid dyes for flow cytometric enumeration of bacteria
      in aquatic systems.
AB  - Seven blue nucleic acid dyes from Molecular Probes Inc. (SYTO-9, SYTO-11, SYTO
      13, SYTO-16, SYTO-BC, SYBR-I and SYBR-II) were compared with the DAPI (4',6
      diamidino-2-phenylindole) method for flow cytometric enumeration of live and
      fixed bacteria in aquatic systems. It was shown that SYBR-II and SYTO-9 are the
      most appropriate dyes for bacterial enumeration in nonsaline waters and can be
      applied to both live and dead bacteria. The fluorescence signal/noise ratio was
      improved when SYTO-9 was used to stain living bacteria in nonsaline waters.
      Inversely, SYBR-II is more appropriate than SYTO dyes for bacterial enumeration
      of unfixed and fixed seawater samples.

PMID- 9572944
TI  - Biodegradation of aliphatic-aromatic copolyesters by Thermomonospora fusca and
      other thermophilic compost isolates.
AB  - Random aliphatic-aromatic copolyesters synthesized from 1,4-butanediol, adipic
      acid, and terephthalic acid (BTA) have excellent thermal and mechanical
      properties and are biodegradable by mixed cultures (e.g., in compost). Over 20
      BTA-degrading strains were isolated by using compost as a microbial source. Among
      these microorganisms, thermophilic actinomycetes obviously play an outstanding
      role and appear to dominate the initial degradation step. Two actinomycete
      strains exhibited about 20-fold higher BTA degradation rates than usually
      observed in a common compost test. These isolates were identified as
      Thermomonospora fusca strains. They appeared to be particularly suitable for
      establishment of rapid degradation tests and were used in comparative studies on
      the biodegradation of various polyesters.

PMID- 9572945
TI  - A mixed culture recovery method indicates that enteric bacteria do not enter the
      viable but nonculturable state.
AB  - A new method, called the mixed culture recovery (MCR) method, has been developed
      to determine whether recovery of culturable bacterial cells from a population of
      largely nonculturable cells is due to resuscitation of the nonculturable cells
      from a viable but nonculturable state or simply to growth of residual culturable
      cells. The MCR method addresses this issue in that it involves the mixing of two
      easily distinguishable strains (e.g., lactose positive and negative) in such a
      way that large numbers of nonculturable cells of both strains are present
      together with a small number of culturable cells of only one strain, performing a
      nutrient addition resuscitation procedure, and then plating the cells to
      determine whether both cell types are recoverable. In repeated experiments with
      strains of Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis,
      Enterobacter aerogenes, and Salmonella choleraesuis, only cells of the culturable
      strain were recovered after application of various resuscitation techniques.
      These results suggest that the nonculturable cells were dead and that the
      apparent resuscitation was merely due to the growth of the remaining culturable
      cells.

PMID- 9572946
TI  - Sensitive and rapid detection of viable Giardia cysts and Cryptosporidium parvum
      oocysts in large-volume water samples with wound fiberglass cartridge filters and
      reverse transcription-PCR.
AB  - We recently described a reverse transcription-PCR (RT-PCR) for detecting low
      numbers of viable Cryptosporidium parvum oocysts spiked into clarified
      environmental water concentrates. We have now modified the assay for direct
      analysis of primary sample concentrates with simultaneous detection of viable C.
      parvum oocysts, Giardia cysts, and a novel type of internal positive control
      (IPC). The IPC was designed to assess both efficiency of mRNA isolation and
      potential RT-PCR inhibition. Sensitivity testing showed that low numbers of
      organisms, in the range of a single viable cyst and oocyst, could be detected
      when spiked into 100-microliter packed pellet volumes of concentrates from creek
      and river water samples. The RT-PCR was compared with an immunofluorescence (IF)
      assay by analyzing 29 nonspiked environmental water samples. Sample volumes of 20
      to 1,500 liters were concentrated with a wound fiberglass cartridge filter.
      Frequency of detection for viable Giardia cysts increased from 24% by IF
      microscopy to 69% by RT-PCR. Viable C. parvum oocysts were detected only once by
      RT-PCR (3%) in contrast to detection of viable Cryptosporidium spp. in four
      samples by IF microscopy (14%), suggesting that Cryptosporidium species other
      than C. parvum were present in the water. This combination of the large-volume
      sampling method with RT-PCR represents a significant advance in terms of
      protozoan pathogen monitoring and in the wider application of PCR technology to
      this field of microbiology.

PMID- 9572947
TI  - Germination, growth, and sporulation of Bacillus thuringiensis subsp. israelensis
      in excreted food vacuoles of the protozoan Tetrahymena pyriformis.
AB  - Spores of Bacillus thuringiensis subsp. israelensis and their toxic crystals are
      bioencapsulated in the protozoan Tetrahymena pyriformis, in which the toxin
      remains stable. Each T. pyriformis cell concentrates the spores and crystals in
      its food vacuoles, thus delivering them to mosquito larvae, which rapidly die.
      Vacuoles containing undigested material are later excreted from the cells. The
      fate of spores and toxin inside the food vacuoles was determined at various times
      after excretion by phase-contrast and electron microscopy as well as by viable
      cell counting. Excreted food vacuoles gradually aggregated, and vegetative growth
      of B. thuringiensis subsp. israelensis was observed after 7 h as filaments that
      stemmed from the aggregates. The outgrown cells sporulated between 27 and 42 h.
      The spore multiplication values in this system are low compared to those obtained
      in carcasses of B. thuringiensis subsp. israelensis-killed larvae and pupae, but
      this bioencapsulation represents a new possible mode of B. thuringiensis subsp.
      israelensis recycling in nontarget organisms.

PMID- 9572948
TI  - Cloning of the xynB gene from Dictyoglomus thermophilum Rt46B.1 and action of the
      gene product on kraft pulp.
AB  - A two-step PCR protocol was used to identify and sequence a family 11 xylanase
      gene from Dictyoglomus thermophilum Rt46B.1. Family 11 xylanase consensus
      fragments (GXCFs) were amplified from Rt46B.1 genomic DNA by using different sets
      of consensus PCR primers that exhibited broad specificity for conserved motifs
      within fungal and/or bacterial family 11 xylanase genes. On the basis of the
      sequences of a representative sample of the GXCFs a single family 11 xylanase
      gene (xynB) was identified. The entire gene sequence was obtained in the second
      step by using genomic walking PCR to amplify Rt46B.1 genomic DNA fragments
      upstream and downstream of the xynB GXCF region. The putative XynB peptide (M(r),
      39,800) encoded by the Rt46B.1 xynB open reading frame was a multidomain enzyme
      comprising an N-terminal catalytic domain (M(r), 22,000) and a possible C
      terminal substrate-binding domain (M(r), 13,000) that were separated by a short
      serine-glycine-rich 23-amino-acid linker peptide. Seven xylanases which differed
      at their N and C termini were produced from different xynB expression plasmids.
      All seven xylanases exhibited optimum activity at pH 6.5. However, the
      temperature optima of the XynB xylanases varied from 70 to 85 degrees C.
      Pretreatment of Pinus radiata and eucalypt kraft-oxygen pulps with XynB resulted
      in moderate xylan solubilization and a substantial improvement in the
      bleachability of these pulps.

PMID- 9572949
TI  - Molecular analysis of a laccase gene from the white rot fungus Pycnoporus
      cinnabarinus.
AB  - It was recently shown that the white rot basidiomycete Pycnoporus cinnabarinus
      secretes an unusual set of phenoloxidases when it is grown under conditions that
      stimulate ligninolysis (C. Eggert, U. Temp, and K.-E. L. Eriksson, Appl. Environ.
      Microbiol. 62:1151-1158, 1996). In this report we describe the results of a
      cloning and structural analysis of the laccase-encoding gene (lcc3-1) expressed
      by P. cinnabarinus during growth under xylidine-induced conditions. The coding
      region of the genomic laccase sequence, which is preceded by the eukaryotic
      promoter elements TATA and CAATA, spans more than 2,390 bp. The corresponding
      laccase cDNA was identical to the genomic sequence except for 10 introns that
      were 50 to 60 bp long. A sequence analysis indicated that the P. cinnabarinus
      lcc3-1 product has a Phe residue at a position likely to influence the reduction
      oxidation potential of the enzyme's type 1 copper center. The P. cinnabarinus
      lcc3-1 sequence was most similar to the sequence encoding a laccase from Coriolus
      hirsutus (level of similarity, 84%).

PMID- 9572950
TI  - Modelling the growth limits (growth/no growth interface) of Escherichia coli as a
      function of temperature, pH, lactic acid concentration, and water activity.
AB  - The form of a previously developed Belehradek type of growth rate model was used
      to develop a probability model for defining the growth/no growth interface as a
      function of temperature (10 to 37 degrees C), pH (pH 2.8 to 6.9), lactic acid
      concentration (0 to 500 mM), and water activity (0.955 to 0.999; NaCl was used as
      the humectant). Escherichia coli was unable to grow in broth in which the
      undissociated lactic acid concentration exceeded 11 mM or, with two exceptions,
      at a pH of 3.9 or less with no lactic acid present. Under experimental conditions
      at which the pH and the undissociated acid concentrations were the major growth
      limiting factors, the growth/no growth interface was essentially independent of
      temperature at temperatures ranging from 15 to 37 degrees C. The interface
      between conditions that allowed growth and conditions at which growth did not
      occur was abrupt. The inhibitory effect of combinations of water activity and pH
      varied with temperature. Predictions of the model for the growth/no growth
      interface were consistent with 95% of the experimental data set.

PMID- 9572951
TI  - Truncation of peptide deformylase reduces the growth rate and stabilizes solvent
      production in Clostridium beijerinckii NCIMB 8052.
AB  - The wild-type strain of Clostridium beijerinckii NCIMB 8052 tends to degenerate
      (i.e., lose the ability to form solvents) after prolonged periods of laboratory
      culture. Several Tn1545 mutants of this organism showing enhanced long-term
      stability of solvent production were isolated. Four of them harbor identical
      insertions within the fms (def) gene, which encodes peptide deformylase (PDF).
      The C. beijerinckii fms gene product contains four diagnostic residues involved
      in the Zn2+ coordination and catalysis found in all PDFs, but it is unusually
      small, because it lacks the dispensable disordered C-terminal domain. Unlike
      previously characterized PDFs from Escherichia coli and Thermus thermophilus, the
      C. beijerinckii PDF can apparently tolerate N-terminal truncation. The Tn1545
      insertion in the mutants is at a site corresponding to residue 15 of the
      predicted gene product. This probably removes 23 N-terminal residues from PDF,
      leaving a 116-residue protein. The mutant PDF retains at least partial function,
      and it complements an fms(Ts) strain of E. coli. Northern hybridizations indicate
      that the mutant gene is actively transcribed in C. beijerinckii. This can only
      occur from a previously unsuspected, outwardly directed promoter located close to
      the right end of Tn1545. The Tn1545 insertion in fms causes a reduction in the
      growth rate of C. beijerinckii, and, associated with this, the bacteria display
      an enhanced stability of solvent production. The latter phenotype can be mimicked
      in the wild type by reducing the growth rate. Therefore, the observed
      amelioration of degeneration in the mutants is probably due to their reduced
      growth rates.

PMID- 9572952
TI  - Brominated Biphenyls Prime Extensive Microbial Reductive Dehalogenation of
      Aroclor 1260 in Housatonic River Sediment
AB  - The upper Housatonic River and Woods Pond (Lenox, Mass.), a shallow impoundment
      on the river, are contaminated with polychlorinated biphenyls (PCBs), the residue
      of partially dechlorinated Aroclor 1260. Certain PCB congeners have the ability
      to activate or "prime" anaerobic microorganisms in Woods Pond sediment to
      reductively dehalogenate the Aroclor 1260 residue. We proposed that brominated
      biphenyls might have the same effect and tested the priming activities of 14 mono
      , di-, and tribrominated biphenyls (350 uM) in anaerobic microcosms of sediment
      from Woods Pond. All of the brominated biphenyls were completely dehalogenated to
      biphenyl, and 13 of them primed PCB dechlorination. Measured in terms of chlorine
      removal and decrease in the proportion of hexa- through nonachlorobiphenyls, the
      microbial PCB dechlorination primed by several brominated biphenyls was nearly
      twice as effective as that primed by chlorinated biphenyls. Congeners containing
      a meta bromine primed Dechlorination Process N (flanked meta dechlorination), and
      congeners containing an unflanked para bromine primed Dechlorination Process P
      (flanked para dechlorination). Two ortho-substituted congeners, 2-bromobiphenyl
      and 2,6-dibromobiphenyl (2-BB and 26-BB), also primed Process N dechlorination.
      The most effective primers were 26-BB, 245-BB, 25-3-BB, and 25-4-BB. The
      microbial dechlorination primed by 26-BB converted ~75% of the hexa- through
      nonachlorobiphenyls to tri- and tetrachlorobiphenyls in 100 days and removed ~75%
      of the PCBs that are most persistent in humans. These results represent a major
      step toward identifying an effective method for accelerating PCB dechlorination
      in situ. The challenge now is to identify naturally occurring compounds that are
      safe and effective primers.

PMID- 9572953
TI  - Ammonia-hyperproducing bacteria from New Zealand ruminants.
AB  - Pasture-grazed dairy cows, deer, and sheep were tested for the presence of
      ammonia-hyperproducing (HAP) bacteria in roll tubes containing a medium in which
      tryptone and Casamino Acids were the sole nitrogen and energy sources. Colonies
      able to grow on this medium represented 5.2, 1.3, and 11.6% of the total
      bacterial counts of dairy cows, deer, and sheep, respectively. A total of 14
      morphologically distinct colonies were purified and studied further. Restriction
      fragment length polymorphisms of 16S rRNA genes indicated that all isolates
      differed from the previously described HAP bacteria, Clostridium aminophilum,
      Clostridium sticklandii, and Peptostreptococcus anaerobius. Carbon source
      utilization experiments showed that five isolates (C2, D1, D4, D5, and S1) were
      unable to use any, or very few, of the carbon sources tested. Biochemical tests
      and phylogenetic analyses of 16S ribosomal DNA sequences indicated that all
      isolates were monensin sensitive; that D1 and S1 belonged to the genus
      Peptostreptococcus, that D4 and D5 belonged to the family Bacteroidaceae, where
      D4 was similar to Fusobacterium necrophorum; and that C2 was most similar to an
      unidentified species from the genus Eubacterium. Growth on liquid medium
      containing tryptone and Casamino Acids as the sole nitrogen and energy source
      showed that D1, D4, and S1 grew rapidly (specific growth rates of 0.40, 0.35, and
      0.29 h-1, respectively), while C2 and D5 were slow growers (0.25 and 0.10 h-1,
      respectively). Ammonia production rates were highest in D1 and D4, which produced
      945.5 and 748.3 nmol/min per mg of protein, respectively. Tests of individual
      nitrogen sources indicated that D1 and D4 grew best on tryptone, S1 grew equally
      well on Casamino Acids or tryptone, and C2 and D5 grew poorly on all nitrogen
      sources. The intact proteins casein and gelatin did not support significant
      growth of any of the isolates. These isolates extend the diversity of known HAP
      rumen bacteria and indicate the presence of significant HAP bacterial populations
      in pasture-grazed New Zealand ruminants.

PMID- 9572954
TI  - Use of inducible feedback-resistant N-acetylglutamate synthetase (argA) genes for
      enhanced arginine biosynthesis by genetically engineered Escherichia coli K-12
      strains.
AB  - The goal of this work was to construct Escherichia coli strains capable of
      enhanced arginine production. The arginine biosynthetic capacity of previously
      engineered E. coli strains with a derepressed arginine regulon was limited by the
      availability of endogenous ornithine (M. Tuchman, B. S. Rajagopal, M. T. McCann,
      and M. H. Malamy, Appl. Environ. Microbiol. 63:33-38, 1997). Ornithine
      biosynthesis is limited due to feedback inhibition by arginine of N
      acetylglutamate synthetase (NAGS), the product of the argA gene and the first
      enzyme in the pathway of arginine biosynthesis in E. coli. To circumvent this
      inhibition, the argA genes from E. coli mutants with feedback-resistant (fbr)
      NAGS were cloned into plasmids that contain "arg boxes," which titrate the ArgR
      repressor protein, with or without the E. coli carAB genes encoding carbamyl
      phosphate synthetase and the argI gene for ornithine transcarbamylase. The free
      arginine production rates of "arg-derepressed" E. coli cells overexpressing
      plasmid-encoded carAB, argI, and fbr argA genes were 3- to 15-fold higher than
      that of an equivalent system overexpressing feedback-sensitive wild-type (wt)
      argA. The expression system with fbr argA produced 7- to 35-fold more arginine
      than a system overexpressing carAB and argI genes on a plasmid in a strain with a
      wt argA gene on the chromosome. The arginine biosynthetic capacity of arg
      derepressed DH5 alpha strains with plasmids containing only the fbr argA gene was
      similar to that of cells with plasmids also containing the carAB and argI genes.
      Plasmids containing wt or fbr argA were stably maintained under normal growth
      conditions for at least 18 generations. DNA sequencing identified different point
      mutations in each of the fbr argA mutants, specifically H15Y, Y19C, S54N, R58H,
      G287S, and Q432R.

PMID- 9572955
TI  - Maximizing plasmid stability and production of released proteins in Yersinia
      enterocolitica.
AB  - Virulent serotypes of Yersinia enterocolitica carry a plasmid (pYV) encoding a
      family of proteins that are released into the medium and whose expression is
      temperature and calcium regulated. The plasmid is easily lost from cells during
      their growth in the laboratory. We have used sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blotting with a monoclonal
      antibody (3.2C) that is specific for a 25-kDa released protein to show that 32
      degrees C is the lowest temperature at which plasmid-encoded proteins are
      expressed in quantity. The highest calcium concentration allowing full expression
      of these proteins was 445 to 545 microM at 32 degrees C. Calcium concentrations
      of 745 microM and above at 37 degrees C completely prevented the loss of pYV
      during multiple subcultures, while at 32 degrees C, calcium concentrations of 245
      microM and greater were sufficient to stabilize the plasmid. Growth of Y.
      enterocolitica at pH 5.5 was slower than at neutral pH values, but it also
      resulted in greatly increased stability of pYV. These studies showed that
      bacterial growth, retention of pYV, and expression of plasmid-encoded proteins
      may be maximized at 32 degrees C with 445 microM calcium and that pYV stability
      is enhanced by growth at low pH. These observations suggest new approaches for
      isolation of plasmid-bearing virulent strains of Y. enterocolitica from samples
      contaminated with this organism and also may improve our understanding of pYV
      retention in vivo.

PMID- 9572956
TI  - Evidence of genomic instability in Campylobacter jejuni isolated from poultry.
AB  - Poultry isolates of Campylobacter jejuni derived from a survey of meat processing
      batches were genotyped by pulsed-field gel electrophoresis (PFGE) of chromosomal
      DNA to establish the clonal relationships between single-colony isolates. In the
      majority of batches studied, one or two genotype patterns predominated. However,
      in one batch (batch A), 21 single-colony isolates gave 14 different PFGE
      genotypes. The banding patterns obtained with SmaI were sufficiently different to
      distinguish between genotypes, although the patterns also produced many common
      bands. The question of whether these isolates represented different clones or had
      a common clonal ancestry was addressed by additional genotypic and phenotypic
      methods. Restriction length polymorphism of PCR products obtained from the
      flagellin genes showed an identical flagellin genotype for all of these isolates.
      In contrast, unrelated control isolates resulted in different flagellin
      genotypes. Moreover, all 14 different PFGE genotypes of batch A had identical
      Penner serotypes and identical or similar biotypes and phage types. It was
      concluded that the isolates were of clonal origin and that the diversity in the
      PFGE banding patterns had most likely originated from genomic rearrangements.
      However, the PFGE genotypes were shown to be stable upon subculturing in vitro
      and after in vivo passage in chickens, and natural transformation between
      isogenic mutants carrying antibiotic markers did not occur in vivo in a chick
      colonization model. The possible mechanisms for the hypothesized genomic
      recombinations and the conditions that allow, induce, or select for such events
      are discussed.

PMID- 9572957
TI  - Comparison of free-living amoebae in hot water systems of hospitals with isolates
      from moist sanitary areas by identifying genera and determining temperature
      tolerance.
AB  - Legionella-contaminated hot water systems and moist sanitary areas in six
      hospitals were sampled for amoebae by following a standardized collection
      protocol. Genus identifications and temperature tolerance determinations were
      made. Amoebae identified as Hartmannella vermiformis (65%), Echinamoebae spp.
      (15%), Saccamoebae spp. (12%), and Vahlkampfia spp. (9%) were detected in 29 of
      56 (52%) hot water samples. Twenty-three of 49 (47%) swabs obtained from moist
      areas were amoeba positive. The following genera were identified: Acanthamoeba
      (22%), Naegleria (22%), Vahlkampfia (20%), Hartmannella (15%), and Vanella (7%).
      The temperature tolerance of amoebae from hot water systems was strikingly
      different from that of amoebae from moist areas. At 44 degrees C on agar, 59% of
      amoebic isolates sampled from hot water systems showed growth. The corresponding
      value for isolates from moist areas was only 17%. Six Acanthamoeba isolates from
      the moist areas were considered potential pathogens. Four Hartmannella and two
      Saccamoeba isolates from hot water could be cultured at 53 degrees C.

PMID- 9572958
TI  - Antibiotic resistance patterns of enterococci and occurrence of vancomycin
      resistant enterococci in raw minced beef and pork in Germany.
AB  - The food chain, especially raw minced meat, is thought to be responsible for an
      increase in the incidence of vancomycin-resistant enterococci (VRE) in human
      nosocomial infections. Therefore, 555 samples from 115 batches of minced beef and
      pork from a European Union-licensed meat-processing plant were screened for the
      occurrence of VRE. The processed meat came from 45 different slaughterhouses in
      Germany. Enterococci were isolated directly from Enterococcosel selective agar
      plates and also from Enterococcosel selective agar plates supplemented with 32 mg
      of vancomycin per liter. In addition, peptone broth was used in a preenrichment
      procedure, and samples were subsequently plated onto Enterococcosel agar
      containing vancomycin. To determine resistance, 209 isolates from 275 samples
      were tested with the glycopeptides vancomycin, teicoplanin, and avoparcin and 19
      other antimicrobial substances by using a broth microdilution test. When the
      direct method was used, VRE were found in 3 of 555 samples (0.5%) at a
      concentration of 1.0 log CFU/g of minced meat. When the preenrichment procedure
      was used, 8% of the samples were VRE positive. Our findings indicate that there
      is a low incidence of VRE in minced meat in Germany. In addition, the resistance
      patterns of the VRE isolates obtained were different from the resistance patterns
      of clinical isolates. A connection between the occurrence of VRE in minced meat
      and nosocomial infections could not be demonstrated on the basis of our findings.

PMID- 9572959
TI  - Cloning and characterization of a prolinase gene (pepR) from Lactobacillus
      rhamnosus.
AB  - A peptidase gene expressing L-proline-beta-naphthylamide-hydrolyzing activity was
      cloned from a gene library of Lactobacillus rhamnosus 1/6 isolated from cheese.
      Peptidase-expressing activity was localized in a 1.5-kb SacI fragment. A sequence
      analysis of the SacI fragment revealed the presence of one complete open reading
      frame (ORF1) that was 903 nucleotides long. The ORF1-encoded 34.2-kDa protein
      exhibited 68% identity with the PepR protein from Lactobacillus helveticus.
      Additional sequencing revealed the presence of another open reading frame (ORF2)
      following pepR; this open reading frame was 459 bp long. Northern (RNA) and
      primer extension analyses indicated that pepR is expressed both as a
      monocistronic transcriptional unit and as a dicistronic transcriptional unit with
      ORF2. Gene replacement was used to construct a PepR-negative strain of L.
      rhamnosus. PepR was shown to be the primary enzyme capable of hydrolyzing Pro-Leu
      in L. rhamnosus. However, the PepR-negative mutant did not differ from the wild
      type in its ability to grow and produce acid in milk. The cloned pepR expressed
      activity against dipeptides with N-terminal proline residues. Also, Met-Ala, Leu
      Leu, and Leu-Gly-Gly and the chromogenic substrates L-leucine-beta-naphthylamide
      and L-phenylalanine-beta-naphthylamide were hydrolyzed by the PepR of L.
      rhamnosus.

PMID- 9572960
TI  - Antibiotic production by Erwinia herbicola Eh1087: its role in inhibition of
      Erwinia amylovora and partial characterization of antibiotic biosynthesis genes.
AB  - Mutants of Erwinia herbicola Eh1087 (Ant-), which did not produce antibiotic
      activity against Erwinia amylovora, the fire blight pathogen, were selected after
      TnphoA mutagenesis. In immature pear fruit Ant- mutants grew at the same rate as
      wild-type strain Eh1087 but did not suppress development of the disease caused by
      E. amylovora. These results indicated that antibiosis plays an important role in
      the suppression of disease by strain Eh1087. All of the Ant- mutations obtained
      were located in a 2.2-kb region on a 200-kb indigenous plasmid. Sequence analysis
      of the mutated DNA region resulted in identification of six open reading frames,
      designated ORF1 through ORF6, four of which were essential to antibiotic
      expression. One gene was identified as a gene which encodes a translocase protein
      which is probably involved in antibiotic secretion. A sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis of plasmid proteins produced in
      Escherichia coli minicells confirmed the presence of proteins whose sizes
      corresponded to the sizes of the predicted open reading frame products.

PMID- 9572961
TI  - New Bradyrhizobium japonicum strains that possess high copy numbers of the
      repeated sequence RS alpha.
AB  - In a survey of DNA fingerprints of indigenous Bradyrhizobium japonicum with the
      species-specific repeated sequences RS alpha and RS beta, 21 isolates from three
      field sites showed numerous RS-specific hybridization bands. The isolates were
      designated highly reiterated sequence-possessing (HRS) isolates, and their DNA
      hybridization profiles were easily distinguished from the normal patterns. Some
      HRS isolates from two field sites possessed extremely high numbers of RS alpha
      copies, ranging from 86 to 175 (average, 128), and showed shifts and duplications
      of nif- and hup-specific hybridization bands. The HRS isolates exhibited slower
      growth than normal isolates, although no difference in symbiotic properties was
      detected between the HRS and normal isolates. Nucleotide sequence analysis of 16S
      rRNA genes showed that HRS isolates were strains of B. japonicum. There was no
      difference in the spectra of serological and hydrogenase groupings of normal and
      HRS isolates. Some HRS isolates possessed a tandem repeat RS alpha dimer that is
      similar to the structure of (IS30)2, which was shown to cause a burst of
      transpositional rearrangements in Escherichia coli. The results suggest that HRS
      isolates are derived from normal isolates in individual fields by genome
      rearrangements that may be mediated by insertion sequences such as RS alpha.

PMID- 9572962
TI  - Genetically engineered Saccharomyces yeast capable of effective cofermentation of
      glucose and xylose.
AB  - Xylose is one of the major fermentable sugars present in cellulosic biomass,
      second only to glucose. However, Saccharomyces spp., the best sugar-fermenting
      microorganisms, are not able to metabolize xylose. We developed recombinant
      plasmids that can transform Saccharomyces spp. into xylose-fermenting yeasts.
      These plasmids, designated pLNH31, -32, -33, and -34, are 2 microns-based high
      copy-number yeast-E. coli shuttle plasmids. In addition to the geneticin
      resistance and ampicillin resistance genes that serve as dominant selectable
      markers, these plasmids also contain three xylose-metabolizing genes, a xylose
      reductase gene, a xylitol dehydrogenase gene (both from Pichia stipitis), and a
      xylulokinase gene (from Saccharomyces cerevisiae). These xylose-metabolizing
      genes were also fused to signals controlling gene expression from S. cerevisiae
      glycolytic genes. Transformation of Saccharomyces sp. strain 1400 with each of
      these plasmids resulted in the conversion of strain 1400 from a non-xylose
      metabolizing yeast to a xylose-metabolizing yeast that can effectively ferment
      xylose to ethanol and also effectively utilizes xylose for aerobic growth.
      Furthermore, the resulting recombinant yeasts also have additional extraordinary
      properties. For example, the synthesis of the xylose-metabolizing enzymes
      directed by the cloned genes in these recombinant yeasts does not require the
      presence of xylose for induction, nor is the synthesis repressed by the presence
      of glucose in the medium. These properties make the recombinant yeasts able to
      efficiently ferment xylose to ethanol and also able to efficiently coferment
      glucose and xylose present in the same medium to ethanol simultaneously.

PMID- 9572963
TI  - Improved Dechlorinating Performance of Upflow Anaerobic Sludge Blanket Reactors
      by Incorporation of Dehalospirillum multivorans into Granular Sludge
AB  - Dechlorination of tetrachloroethene, also known as perchloroethylene (PCE), was
      investigated in an upflow anaerobic sludge blanket (UASB) reactor after
      incorporation of the strictly anaerobic, reductively dechlorinating bacterium
      Dehalospirillum multivorans into granular sludge. This reactor was compared to
      the reference 1 (R1) reactor, where the granules were autoclaved to remove all
      dechlorinating abilities before inoculation, and to the reference 2 (R2) reactor,
      containing only living granular sludge. All three reactors were fed mineral
      medium containing 3 to 57 uM PCE, 2 mM formate, and 0.5 mM acetate and were
      operated under sterile conditions. In the test reactor, an average of 93%
      (mole/mole) of the effluent chloroethenes was dichloroethene (DCE), compared to
      99% (mole/mole) in the R1 reactor. The R2 reactor, with no inoculation, produced
      only trichloroethene (TCE), averaging 43% (mole/mole) of the effluent
      chloroethenes. No dechlorination of PCE was observed in an abiotic control
      consisting of sterile granules without inoculum. During continuous operation with
      stepwise-reduced hydraulic retention times (HRTs), both the test reactor and the
      R1 reactor showed conversion of PCE to DCE, even at HRTs much lower than the
      reciprocal maximum specific growth rate of D. multivorans, indicating that this
      bacterium was immobilized in the living and autoclaved granular sludge. In
      contrast, the R2 reactor, with no inoculation of D. multivorans, only converted
      PCE to TCE under the same conditions. Immobilization could be confirmed by using
      fluorescein-labeled antibody probes raised against D. multivorans. In granules
      obtained from the R1 reactor, D. multivorans grew mainly in microcolonies located
      in the centers of the granules, while in the test reactor, the bacterium mainly
      covered the surfaces of granules.

PMID- 9572964
TI  - Rapid Consumption of Low Concentrations of Methyl Bromide by Soil Bacteria
AB  - A dynamic dilution system for producing low mixing ratios of methyl bromide
      (MeBr) and a sensitive analytical technique were used to study the uptake of MeBr
      by various soils. MeBr was removed within minutes from vials incubated with soils
      and ~10 parts per billion by volume of MeBr. Killed controls did not consume
      MeBr, and a mixture of the broad-spectrum antibiotics chloramphenicol and
      tetracycline inhibited MeBr uptake by 98%, indicating that all of the uptake of
      MeBr was biological and by bacteria. Temperature optima for MeBr uptake suggested
      a biological sink, yet soil moisture and temperature optima varied for different
      soils, implying that MeBr consumption activity by soil bacteria is diverse. The
      eucaryotic antibiotic cycloheximide had no effect on MeBr uptake, indicating that
      soil fungi were not involved in MeBr removal. MeBr consumption did not occur
      anaerobically. A dynamic flowthrough vial system was used to incubate soils at
      MeBr mixing ratios as low as those found in the remote atmosphere (5 to 15 parts
      per trillion by volume [pptv]). Soils consumed MeBr at all mixing ratios tested.
      Temperate forest and grassy lawn soils consumed MeBr most rapidly (rate constant
      [k] = 0.5 min-1), yet sandy temperate, boreal, and tropical forest soils also
      readily consumed MeBr. Amendments of CH4 up to 5% had no effect on MeBr uptake
      even at CH4:MeBr ratios of 10(7), and depth profiles of MeBr and CH4 consumption
      exhibited very different vertical rate optima, suggesting that methanotrophic
      bacteria, like those presently in culture, do not utilize MeBr when it is at
      atmospheric mixing ratios. Data acquired with gas flux chambers in the field
      demonstrated the very rapid in situ consumption of MeBr by soils. Uptake of MeBr
      at mixing ratios found in the remote atmosphere occurs via aerobic bacterial
      activity, displays first-order kinetics at mixing ratios from 5 pptv to ~1 part
      per million per volume, and is rapid enough to account for 25% of the global
      annual loss of atmospheric MeBr.

PMID- 9572965
TI  - Molecular analysis of the locus responsible for production of plantaricin S, a
      two-peptide bacteriocin produced by Lactobacillus plantarum LPCO10.
AB  - A 4.5-kb region of chromosomal DNA carrying the locus responsible for the
      production of plantaricin S, a two-peptide bacteriocin produced by Lactobacillus
      plantarum LPCO10 (R. Jimenez-Diaz, J. L. Ruiz-Barba, D. P. Cathcart, H. Holo, I.
      F. Nes, K. H. Sletten, and P. J. Warner, Appl. Environ. Microbiol. 61:4459-4463,
      1995), has been cloned, and the nucleotide sequence has been elucidated. Two
      genes, designated plsA and plsB and encoding peptides alpha and beta,
      respectively, of plantaricin S, plus an open reading frame (ORF), ORF2, were
      found to be organized in an operon. Northern blot analysis showed that these
      genes are cotranscribed, giving a ca. 0.7-kb mRNA, whose transcription start
      point was determined by primer extension. Nucleotide sequences of plsA and plsB
      revealed that both genes are translated as bacteriocin precursors which include N
      terminal leader sequences of the double-glycine type. The role of ORF2 is unknown
      at the moment, although it might be expected to encode an immunity protein of the
      type described for other bacteriocin operons. In addition, several other
      potential ORFs have been found, including some which may be responsible for the
      regulation of bacteriocin production. Two of them, ORF8 and ORF14, show strong
      homology with histidine protein kinase and response regulator genes,
      respectively, which have been found to be involved in the regulation of the
      production of other bacteriocins from lactic acid bacteria. A third ORF, ORF5,
      shows homology with gene agrB from Staphylococcus aureus, which is involved in
      the mechanism of regulation of the virulence phenotype in this species. Thus, an
      agr-like regulatory system for the production of plantaricin S is postulated.

PMID- 9572966
TI  - Microbiology of a nitrite-oxidizing bioreactor.
AB  - The microbiology of the biomass from a nitrite-oxidizing sequencing batch reactor
      (NOSBR) fed with an inorganic salts solution and nitrite as the sole energy
      source that had been operating for 6 months was investigated by microscopy, by
      culture-dependent methods, and by molecular biological methods, and the seed
      sludge that was used to inoculate the NOSBR was investigated by molecular
      biological methods. The NOSBR sludge comprised a complex and diverse microbial
      community containing gram-negative and gram-positive rods, cocci, and filaments.
      By culture-dependent methods (i.e., micromanipulation and sample dilution and
      spread plate inoculation), 16 heterotrophs (6 gram positive and 10 gram negative)
      were identified in the NOSBR sludge (RC), but no autotrophs were isolated. 16S
      ribosomal DNA clone libraries of the two microbial communities revealed that the
      seed sludge (GC) comprised a complex microbial community dominated by
      Proteobacteria (29% beta subclass; 18% gamma subclass) and high G + C gram
      positive bacteria (10%). Three clones (4%) were closely related to the
      autotrophic nitrite-oxidizer Nitrospira moscoviensis. The NOSBR sludge was
      overwhelmingly dominated by bacteria closely related to N. moscoviensis (89%).
      Two clone sequences were similar to those of the genus Nitrobacter. Near-complete
      insert sequences of eight RC and one GC N. moscoviensis clone were determined and
      phylogenetically analyzed. This is the first report of the presence of bacteria
      from the Nitrospira phylum in wastewater treatment systems, and it is
      hypothesized that these bacteria are the unknown nitrite oxidizers in these
      processes.

PMID- 9572967
TI  - Oxidation of Methyl-Substituted Naphthalenes: Pathways in a Versatile
      Sphingomonas paucimobilis Strain
AB  - Aromatic compounds with alkyl substituents are abundant in fossil fuels. These
      compounds become important environmental sources of soluble toxic products,
      developmental inhibitors, etc. principally through biological activities. To
      assess the effect of methyl substitution on the completeness of mineralization
      and accumulation of pathway products, an isolate from a phenanthrene enrichment
      culture, Sphingomonas paucimobilis 2322, was used. Washed cell suspensions
      containing cells grown on 2,6-dimethylnaphthalene in mineral medium were
      incubated with various mono-, di-, and trimethylnaphthalene isomers, and the
      products were identified and quantified by gas chromatography and mass
      spectrometry. The data revealed enzymes with relaxed substrate specificity that
      initiate metabolism either by methyl group monoxygenation or by ring
      dioxygenation. Congeners with a methyl group on each ring initially hydroxylate a
      methyl, and this is followed by conversion to a carboxyl; when there are two
      methyl groups on a single ring, the first reaction is aryl dioxygenation of the
      unsubstituted ring. Intermediates are channeled to primary ring fission via
      dihydrodiols to form methyl-substituted salicylates. Further evidence that there
      are multiple pathways comes from the fact that both phthalate and
      (methyl)salicylate are formed from 2-methylnaphthalene.

PMID- 9572968
TI  - Ecophysiological and phylogenetic studies of Nevskia ramosa in pure culture.
AB  - During the last 100 years, the neuston bacterium Nevskia ramosa has been
      described several times. This bacterium forms conspicuous rosette-like
      microcolonies at the air-water interface. In this study, pure cultures of Nevskia
      ramosa were obtained for the first time, from a bog lake (strain Soe1, DSMZ
      11499T) and a freshwater ditch (strain OL1, DSMZ 11500). The isolates showed
      special adaptations to life in the epineuston. They formed hydrophobic surface
      films with a dull appearance. N. ramosa is sensitive to UV radiation but revealed
      a very effective photorepair mechanism. Exposure to light at a wavelength of 350
      nm after UV treatment raised the number of surviving cells by several orders of
      magnitude. The isolates grew with a broad range of organic substrates. Surface
      films were formed only in the absence of combined nitrogen; however, nitrogenase
      activity was not detected. It appears that during growth at the air-water
      interface the cells benefit from trapping ammonia from the air. The G + C content
      of the DNA was 67.8 and 69.0 mol% for strains Soe1 and OL1, respectively. The
      slight difference was confirmed by enterobacterial repetitive intergenic
      consensus PCR. The 16S rRNA sequences revealed 99.2% similarity. Thus, both
      isolates belong to the same species. The phylogenetic analysis indicated that
      Nevskia is a member of the gamma-subclass Proteobacteria that has no known close
      relatives.

PMID- 9572969
TI  - Phylogeny and identification in situ of Nevskia ramosa.
AB  - An enrichment of the neuston bacterium Nevskia ramosa was investigated by the
      cultivation-independent rRNA approach. N. ramosa was first described by Famintzin
      in 1892 as a rod-shaped, slightly bent bacterium forming typical flat rosettes on
      the surface of shallow freshwater habitats by unilateral slime formation. PCR in
      combination with cloning and sequencing was used for retrieving 21 partial and 5
      nearly full-length 16S rRNA sequences forming three tight clusters. In situ
      hybridization with rRNA-targeted oligonucleotide probes allowed us to assign the
      three sequence clusters to three distinct bacterial populations abundant in the
      enrichment. The two probes that unambiguously identified the N. ramosa morphotype
      were derived from a 16S rRNA sequence that had similarities of 87.9 to 88.9% to
      the rRNA sequences of the most closely related group in the database, Xanthomonas
      sp. and relatives. N. ramosa currently is the only representative of an
      independent, deep branch of the gamma subclass of the class Proteobacteria. The
      two other populations abundant in the enrichment were affiliated with the alpha
      subclass of the class Proteobacteria. They were most closely related to
      Blastobacter sp. (97.2% similarity) and Mycoplana bullata (97.6% similarity) and
      might represent new species in the respective genera.

PMID- 9572970
TI  - Effect of bacterial distribution and activity on conjugal gene transfer on the
      phylloplane of the bush bean (Phaseolus vulgaris).
AB  - Conjugal plasmid transfer was examined on the phylloplane of bean (Phaseolus
      vulgaris) and related to the spatial distribution pattern and metabolic activity
      of the bacteria. The donor (Pseudomonas putida KT2442) harbored a derivative of
      the TOL plasmid, which conferred kanamycin resistance and had the gfp gene
      inserted downstream of a lac promoter. A chromosomal insertion of lacIq prevented
      expression of the gfp gene. The recipient (P. putida KT2440) had a chromosomal
      tetracycline resistance marker. Thus, transconjugants could be enumerated by
      plating and visualized in situ as green fluorescent cells. Sterile bean seedlings
      were inoculated with donors and recipients at densities of approximately 10(5)
      cells per cm2. To manipulate the density and metabolic activity (measured by
      incorporation of [3H]leucine) of the inoculated bacteria, plants were grown at
      various relative humidities (RH). At 100% RH, the transconjugants reached a
      density of 3 x 10(3) CFU/cm2, corresponding to about one-third of the recipient
      population. At 25% RH, numbers of transconjugants were below the detection limit.
      Immediately after inoculation onto the leaves, the per-cell metabolic activity of
      the inocula increased by up to eight times (100% RH), followed by a decrease to
      the initial level after 96 h. The metabolic activity of the bacteria was not rate
      limiting for conjugation, and no correlation between the two parameters was
      observed. Apparently, leaf exudates insured that the activity of the bacteria was
      above a threshold value for transfer to occur. Transconjugants were primarily
      observed in junctures between epidermal cells and in substomatal cavities. The
      distribution of the transconjugants was similar to the distribution of indigenous
      bacteria on nonsterile leaves. Compared to polycarbonate filters, with cell
      densities equal to the overall density on the leaves, transfer ratios on leaves
      were up to 30 times higher. Thus, aggregation of the bacteria into microhabitats
      on the phylloplane had a great stimulatory effect on transfer.

PMID- 9572971
TI  - Grazing Pressure by a Bacterivorous Flagellate Reverses the Relative Abundance of
      Comamonas acidovorans PX54 and Vibrio Strain CB5 in Chemostat Cocultures
AB  - The response of the bacterial strains Comamonas acidovorans PX54 (beta subclass
      of the class Proteobacteria) and Vibrio strain CB5 (gamma subclass of the class
      Proteobacteria) to grazing by the bacterivorous flagellate Ochromonas sp. was
      examined in one-stage chemostat experiments under conditions of low growth rates
      with a complex carbon source. The two bacterial strains were cultured together;
      they were cultured without flagellates in the first phase of the experiments and
      in the presence of the flagellates in the second phase. Monoclonal and polyclonal
      antibodies were used to determine the numbers and sizes of C. acidovorans PX54
      and Vibrio strain CB5 cells. The flagellates caused strong changes in total
      bacterial cell numbers, in the relative abundances of the individual bacterial
      strains, and in bacterial cell size distribution. Vibrio strain CB5 dominated the
      total bacterial cell numbers during the flagellate-free phase of the experiments
      with a relative abundance of 93%, but this declined to 33% after inoculation with
      the flagellate. In contrast to Vibrio strain CB5, C. acidovorans PX54 responded
      to grazing with a strong expansion of cell length distribution toward large,
      filamentous cells. These changes in cell morphology resulted in a high percentage
      of inedible cells in the C. acidovorans PX54 population but not in the Vibrio
      strain CB5 population, which caused the observed change in the relative
      abundances of the strains. Batch culture experiments without the flagellate
      demonstrated that the elongation of C. acidovorans PX54 cells was dependent on
      their growth rate. This indicates that the occurrence of filamentous C.
      acidovorans PX54 cells is not a direct response to chemical stimuli released by
      the flagellates but rather a response to increased growth rates due to flagellate
      grazing.

PMID- 9572972
TI  - arfI and arfII, two genes encoding alpha-L-arabinofuranosidases in Cytophaga
      xylanolytica.
AB  - arfI encoded the 57.7-kDa subunit of Cytophaga xylanolytica arabinofuranosidase I
      (ArfI). arfII encoded a 59.2-kDa subunit of ArfII. Products of both cloned genes
      liberated arabinose from arabinan and arabinoxylan. The deduced amino acid
      sequences of ArfI and ArfII revealed numerous regions that were identical to each
      other and to regions of homologous proteins from Bacteroides ovatus, Bacillus
      subtilis, and Clostridium stercorarium.

PMID- 9572973
TI  - Phanerochaete chrysosporium cellobiohydrolase and cellobiose dehydrogenase
      transcripts in wood.
AB  - The transcripts of structurally related cellobiohydrolase genes in Phanerochaete
      chrysosporium-colonized wood chips were quantified. The transcript patterns
      obtained were dramatically different from the transcript patterns obtained
      previously in defined media. Cellobiose dehydrogenase transcripts were also
      detected, which is consistent with the hypothesis that such transcripts play an
      important role in cellulose degradation.

PMID- 9572974
TI  - Purification of Extracellular Cholesterol Oxidase with High Activity in the
      Presence of Organic Solvents from Pseudomonas sp. Strain ST-200
AB  - Extracellular cholesterol oxidase of Pseudomonas sp. strain ST-200 was purified
      from the culture supernatant. This oxidase contained bound flavin and was
      categorized as a 3beta-hydroxysteroid oxidase, converting 3beta-hydroxyl groups
      to keto groups. The molecular mass was 60 kDa. The enzyme was stable at pH 4 to
      11 and active at pH 5.0 to 8.5, showing optimal activity at pH 7 at 60 degreesC.
      The Michaelis constant of the ST-200 cholesterol oxidase was lower than those of
      commercially available oxidases. The cholesterol oxidation rate was enhanced 3-
      to 3.5-fold in the presence of organic solvents, with log Pow values (partition
      coefficients of the organic solvent between n-octanol and water), in the range of
      2.1 to 4.2, compared with that in the absence of organic solvents.

PMID- 9572975
TI  - Chloromethane Metabolism by Methylobacterium sp. Strain CM4
AB  - Methylobacterium sp. strain CM4 metabolized chloromethane quantitatively with a
      molar yield of 2.8 g of whole-cell protein/mol of C. This value was similar to
      that observed after growth with methanol (2.9 g of protein/mol of C) and about
      three times larger than the yield with formate (0.94 g of protein/mol of C).
      Chloromethane dehalogenation activity was inducible. MiniTn5 transposon insertion
      mutants with altered growth characteristics with chloromethane and other C1
      compounds were isolated and characterized. Nine of these were unable to grow with
      chloromethane but were able to grow with methanol, methylamine, or formate.
      Seventy-three transposon mutants that were defective in the utilization of either
      methanol, methylamine, methanol plus methylamine, or formate could still grow
      with chloromethane. Based on the protein yield data and the properties of the
      transposon mutants, we propose a pathway for chloromethane metabolism that
      depends on methyltransferase and dehydrogenase activities.

PMID- 9572976
TI  - Rapid Benzene Degradation in Methanogenic Sediments from a Petroleum-Contaminated
      Aquifer
AB  - In methanogenic sediments from a petroleum-contaminated aquifer, [14C]benzene was
      converted to 14CH4 and 14CO2 without an apparent lag. Phenol, acetate, and
      propionate were intermediates in benzene mineralization. These results suggest
      that alternative electron acceptors need not be available for there to be
      significant natural attenuation of benzene in some petroleum-contaminated
      aquifers.

PMID- 9572977
TI  - Structures of homologous composite transposons carrying cbaABC genes from Europe
      and North America.
AB  - IS1071 is a class II transposable element carrying a tnpA gene related to the
      transposase genes of the Tn3 family. Copies of IS1071 that are conserved with
      more than 99% nucleotide sequence identity have been found as direct repeats
      flanking a remarkable variety of catabolic gene sequences worldwide. The
      sequences of chlorobenzoate catabolic transposons found on pBRC60 (Tn5271) in
      Niagara Falls, N.Y., and on pCPE3 in Bologna, Italy, show that these transposons
      were formed from highly homologous IS1071 and cbaABC components (levels of
      identity, > 99.5 and > 99.3%, respectively). Nevertheless, the junction sequences
      between the IS1071L and IS1071R elements and the internal DNA differ by 41 and
      927 bp, respectively, suggesting that these transposons were assembled
      independently on the two plasmids. The formation of the right junction in both
      transposons truncated an open reading frame for a putative aryl-coenzyme A ligase
      with sequence similarity to benzoate- and p-hydroxybenzoate-coenzyme A ligases of
      Rhodopseudomonas palustris.

PMID- 9572978
TI  - Cloning of the ribosomal protein L41 gene of Phaffia rhodozyma and its use a drug
      resistance marker for transformation.
AB  - The ribosomal protein L41 gene of Phaffia rhodozyma was cloned and used as a
      dominant selectable marker for cycloheximide resistance in the transformation of
      P. rhodozyma. Electrotransformation with a plasmid containing a ribosomal DNA
      fragment as a targeting signal typically yielded 800 to 1,200
      transformants/microgram of DNA with an integrated copy number of about seven per
      haploid genome.

PMID- 9572979
TI  - Lysis of Lactococcus lactis subsp. cremoris SK110 and its nisin-immune
      transconjugant in relation to flavor development in cheese.
AB  - To develop a nisin-producing cheese starter, Lactococcus lactis subsp. cremoris
      SK110 was conjugated with transposon Tn5276-NI, which codes for nisin immunity
      but not for nisin production. Cheese made with transconjugant SK110::Tn5276-NI as
      the starter was bitter. The muropeptide of the transconjugant contained a
      significantly greater amount of tetrapeptides than the muropeptide of strain
      SK110, which could have decreased the susceptibility of the cells to lysis and
      thereby the release of intracellular debittering enzymes.

PMID- 9572980
TI  - Differentiation of Cryptosporidium parvum isolates by a simplified randomly
      amplified polymorphic DNA technique.
AB  - Genomic DNA was isolated from Cryptosporidium parvum oocysts by a specific
      immunomagnetic separation-in vitro excystation procedure and subjected to
      randomly amplified polymorphic DNA analysis using sequence-independent primers.
      An estuary C. parvum isolate was easily differentiated from several bovine
      isolates, while five bovine isolates of the same origin were indistinguishable
      from each other.

PMID- 9572981
TI  - Small, Acid-Soluble Spore Proteins of the alpha/beta Type Do Not Protect the DNA
      in Bacillus subtilis Spores against Base Alkylation
AB  - Ethyl methanesulfonate (EMS) killed wild-type Bacillus subtilis spores as rapidly
      as spores lacking small, acid-soluble proteins (SASP) of the alpha/beta type
      (alpha-beta- spores), and 20% of the survivors had obvious mutations. A recA
      mutation increased the EMS sensitivity of wild-type and alpha-beta- spores
      similarly but reduced their mutagenesis; EMS treatment of dormant spores also
      resulted in the induction of RecA synthesis during spore germination. EMS
      generated similar levels of alkylated bases in wild-type and alpha-beta- spore
      DNAs, in purified DNA, or in DNA saturated with alpha/beta-type SASP. Ethylene
      oxide (EtO) also generated similar levels of base alkylation in wild-type and
      alpha-beta- spore DNAs. These data indicate that EMS and EtO kill spores at least
      in part by DNA damage but that alpha/beta-type SASP, which protect DNA against
      many types of damage, do not protect spore DNA from base alkylation.

PMID- 9572982
TI  - Regulation of lipid synthesis in Bradyrhizobium japonicum: low oxygen
      concentrations trigger phosphatidylinositol biosynthesis.
AB  - Lowering oxygen tension in free-living Bradyrhizobium japonicum resulted in a
      dramatic switch of membrane chemistry in which phosphatidylcholine, the
      predominant lipid in aerated cultures, was no longer synthesized and
      phosphatidylethanolamine became the major lipid. Besides this change,
      phosphatidylinositol, a typical plant lipid rarely found in bacteria, was also
      synthesized.

PMID- 9572983
TI  - Endopolygalacturonase PG1 in Different Formae Speciales of Fusarium oxysporum
AB  - PG1, the major endopolygalacturonase of the vascular wilt pathogen Fusarium
      oxysporum, was secreted during growth on pectin by 10 of 12 isolates belonging to
      seven formae speciales, as determined with isoelectric focusing zymograms and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. A Southern
      analysis of genomic DNA and PCR performed with gene-specific primers revealed
      that the pg1 locus was highly conserved structurally in most isolates. Two PG1
      deficient isolates were identified; one lacked the encoding gene, and the other
      carried a pg1 allele disrupted by a 3.2-kb insertion with sequence homology to
      hAT transposases. The virulence for muskmelon of different F. oxysporum f. sp.
      melonis isolates was not correlated with PG1 production in vitro. We concluded
      that PG1 is widely distributed in F. oxysporum and that it is not essential for
      pathogenicity.

PMID- 9572984
TI  - Evaluation of structurally different carotenoids in Escherichia coli
      transformants as protectants against UV-B radiation.
AB  - Escherichia coli cells transformed with several carotenogenic genes to mediate
      the formation of zeta-carotene, neurosporene, lycopene, beta-carotene, and
      zeaxanthin were exposed to UV-B radiation. Short-term kinetics revealed that
      endogenous levels of neurosporene and beta-carotene protected E. coli against
      irradiation with UV-B. Zeaxanthin protected against only the photosensitized UV-B
      treatment. All other carotenoids were ineffective.

PMID- 9572985
TI  - Effect of dietary stress on fecal shedding of Escherichia coli O157:H7 in calves.
AB  - Two groups of calves were subjected to dietary stress by withholding of food
      beginning 1 or 14 days after inoculation with 10(10) CFU of Escherichia coli
      O157:H7. Following treatment, neither group had a significant increase in fecal
      shedding of E. coli O157:H7. A third group of calves had food withheld for 48 h
      prior to inoculation with 10(7) CFU of E. coli O157:H7. These calves were more
      susceptible to infection and shed significantly more E. coli O157:H7 organisms
      than calves maintained on a normal diet.

PMID- 9572986
TI  - Diversity of European Lyme disease spirochetes at the southern margin of their
      range.
AB  - We determined whether the genospecies diversity of Lyme disease spirochetes in
      vector ticks questing on a subtropical island is as broad as that in Central
      Europe. Although spirochetes infected < 1% of the ticks sampled on Madeira
      Island, these infections included all three genospecies implicated in human
      disease. Therefore, spirochetal diversity is as great at the southern margin as
      it is in the center of this pathogen's range.

PMID- 9572987
TI  - A PCR detection method for rapid identification of Melissococcus pluton in
      honeybee larvae.
AB  - Melissococcus pluton is the causative agent of European foulbrood, a disease of
      honeybee larvae. This bacterium is particularly difficult to isolate because of
      its stringent growth requirements and competition from other bacteria. PCR was
      used selectively to amplify specific rRNA gene sequences of M. pluton from pure
      culture, from crude cell lysates, and directly from infected bee larvae. The PCR
      primers were designed from M. pluton 16S rRNA sequence data. The PCR products
      were visualized by agarose gel electrophoresis and confirmed as originating from
      M. pluton by sequencing in both directions. Detection was highly specific, and
      the probes did not hybridize with DNA from other bacterial species tested. This
      method enabled the rapid and specific detection and identification of M. pluton
      from pure cultures and infected bee larvae.

PMID- 9572988
TI  - Endothelial cells in physiology and in the pathophysiology of vascular disorders.

PMID- 9572989
TI  - Prothrombin G20210A mutant genotype is a risk factor for cerebrovascular ischemic
      disease in young patients.
AB  - The factor II G20210A mutation is a recently identified congenital risk factor
      for venous thrombosis. Its role in artery disease is still undefined. We
      investigated 72 patients (35 male and 37 female) with documented ischemic stroke
      occurred before 50 years of age and without risk factors such as diabetes,
      hypertension, and hyperlipidemia; 198 thrombosis-free individuals were
      investigated as the control group. We found 7 heterozygotes (9.7%) and 2
      homozygotes (2.7%) for the mutant factor II allele among the patients and 5
      heterozygotes (2.5%) among the controls; the mutant factor II allele frequency in
      the patient group (7.6%, 95% confidence interval [CI], 3.3 to 11.9) was
      significantly higher than in the controls (1.2%; 95% CI, 0.1 to 2.3; P = .0001).
      The prevalence of other investigated mutant alleles (factor V G1691A,
      methylenetetrahydrofolate reductase C677T) did not significantly differ between
      the two groups. The odds ratio for ischemic stroke associated with the
      carriership of the mutant factor II allele (both heterozygous and homozygous
      genotypes) was 5.1 (95% CI, 1.6 to 16.3). Heterozygous genotype was associated
      with a 3.8-fold increased risk for cerebral ischemia (95% CI, 1.1 to 13.1); in
      particular, assuming an expected prevalence of homozygotes in the general
      population of 1.6 to 10,000 according to the Hardy-Weinberg equilibrium, the risk
      associated with the homozygous genotype was estimated exceedingly high, being
      increased 208-fold.

PMID- 9572990
TI  - Activation of Stat-3 is involved in the induction of apoptosis after ligation of
      major histocompatibility complex class I molecules on human Jurkat T cells.
AB  - Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators
      of transcription (Stat) after ligation of major histocompatibility complex class
      I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated
      tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3. In addition, the
      transcription factor Stat-3 was tyrosine phosphorylated in the cytoplasm and
      subsequently translocated to the cell nucleus. Data obtained by electrophoretic
      mobility shift assay suggested that the activated Stat-3 protein associates with
      the human serum-inducible element (hSIE) DNA-probe derived from the interferon
      gamma activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat
      protein binding. An association between hSIE and Stat-3 after MHC-I ligation was
      directly demonstrated by precipitating Stat-3 from nuclear extracts with
      biotinylated hSIE probe and avidin-coupled agarose. To investigate the function
      of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat
      3 isoform lacking the transactivating domain. This dominant-negative acting Stat
      3 isoform significantly inhibited apoptosis induced by ligation of MHC-I. In
      conclusion, our data suggest the involvement of the Jak/Stat signal pathway in
      MHC-I-induced signal transduction in T cells.

PMID- 9572991
TI  - Genetic polymorphisms in the tumor necrosis factor locus influence non-Hodgkin's
      lymphoma outcome.
AB  - Systemic release of tumor necrosis factor (TNF) and lymphotoxin-alpha (LTalpha)
      has been found to contribute to the severity of non-Hodgkin's lymphoma (NHL). We
      investigated whether genetic polymorphisms in the TNF locus, previously shown to
      influence TNF and LTalpha genes expression, might contribute to these cytokines
      production and to the clinical course of NHL. Genomic DNA from 273 lymphoma
      patients was typed for TNF (-308) polymorphism using an allele-specific
      polymerase chain reaction (PCR) and for LTalpha (+252) polymorphism with a PCR
      based restriction fragment length polymorphism. The presence of the TNF allele
      involved in increased TNF gene transcription was associated with higher plasma
      levels of this cytokine at the time of lymphoma diagnosis (chi2 test, P = .013).
      An extended haplotype analysis showed that the presence of at least two TNF or
      LTalpha high-producer alleles constituted a risk factor for first-line treatment
      failure (chi2 test, P = .021), shorter progression-free survival (log-rank test,
      P = .0007), and overall survival (log-rank test, P = .012). In the subgroup of
      126 patients with diffuse large-cell lymphoma, the presence of two or more
      TNF/LTalpha high producing alleles contributed significantly to a higher rate of
      relapse and progression (log-rank test, P = .045 and P = .027). In multivariate
      Cox regression models including the variables of the International Prognostic
      Index, the TNF/LTalpha haplotype status was found to be an independent risk
      factor for progression-free survival (relative risk 2.33, 95% confidence interval
      [1.17 to 4.64], P = . 0053) and overall survival (relative risk 1.92, 95%
      confidence interval [0.63 to 5.80], P = .081) of large-cell lymphoma patients.
      These results indicate that genetic polymorphism leading to increased TNF
      production influences the outcome of NHL and suggest a pathophysiological role
      for the genetic control of the immune response in lymphoid malignancies.

PMID- 9572992
TI  - Progressive telomere shortening in aplastic anemia.
AB  - Improved survival in aplastic anemia (AA) has shown a high incidence of late
      clonal marrow disorders. To investigate whether accelerated senescence of
      hematopoietic stem cells might underlie the pathophysiology of myelodysplasia
      (MDS) or paroxysmal nocturnal hemoglobinuria (PNH) occurring as a late
      complication of AA, we studied mean telomere length (TRF) in peripheral blood
      leukocytes from 79 patients with AA, Fanconi anemia, or PNH in comparison with
      normal controls. TRF lengths in the patient group were significantly shorter for
      age than normals (P < .0001). Telomere shortening was apparent in both
      granulocyte and mononuclear cell fractions, suggesting loss at the level of the
      hematopoietic stem cell. In patients with acquired AA with persistent cytopenias
      (n = 40), there was significant correlation between telomere loss and disease
      duration (r = -.685; P < .0001), equivalent to progressive telomere erosion at
      216 bp/yr, in addition to the normal age-related loss. In patients who had
      achieved normal full blood counts (n = 20), the rate of telomere loss had
      apparently stabilised. There was no apparent association between telomere loss
      and secondary PNH (n = 13). However, of the 5 patients in the study with TRF less
      than 5.0 kb, 3 had acquired cytogenetic abnormalities, suggesting that telomere
      erosion may be relevant to the pathogenesis of MDS in aplastic anemia.

PMID- 9572993
TI  - The human intrinsic factor-vitamin B12 receptor, cubilin: molecular
      characterization and chromosomal mapping of the gene to 10p within the autosomal
      recessive megaloblastic anemia (MGA1) region.
AB  - Uptake of vitamin B12 (cyanocobalamin) is facilitated by the cobalamin-binder
      gastric intrinsic factor (IF), which recognizes a 460-kD receptor, cubilin,
      present in the epithelium of intestine and kidney. Surface plasmon resonance
      analysis of ligand-affinity-purified human cubilin demonstrated a high-affinity
      calcium- and cobalamin-dependent binding of IF-cobalamin. Complete cDNA cloning
      of the human receptor showed a 3597 amino acid peripheral membrane protein with
      69% identity to rat cubilin. Amino-terminal sequencing of the receptor indicates
      that the cDNA sequence encodes a precursor protein undergoing proteolytic
      processing due to cleavage at a recognition site (Arg7-Glu8-Lys9-Arg) for the
      trans-Golgi proteinase furin. Using fluorescence in situ hybridization, radiation
      hybrid mapping, and screening of YAC clones, the human cubilin gene was mapped
      between the markers D10S1661 and WI-5445 on the short arm of chromosome 10. This
      is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region
      harboring the unknown recessive-gene locus of juvenile megaloblastic anemia
      caused by intestinal malabsorption of cobalamin (Imerslund-Grasbeck's disease).
      In conclusion, the present molecular and genetic information on human cubilin now
      provides circumstantial evidence that an impaired synthesis, processing, or
      ligand binding of cubilin is the molecular background of this hereditary form of
      megaloblastic anemia.

PMID- 9572994
TI  - Safety and cost effectiveness of a 10 x 10(9)/L trigger for prophylactic platelet
      transfusions compared with the traditional 20 x 10(9)/L trigger: a prospective
      comparative trial in 105 patients with acute myeloid leukemia.
AB  - In 105 consecutive patients with de novo acute myeloid leukemia (French-American
      British M3 excluded), we compared prospectively the risk of bleeding
      complications, the number of platelet and red blood cell transfusions
      administered, and the costs of transfusions using two different prophylactic
      platelet transfusion protocols. Two hundred sixteen cycles of induction or
      consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 x
      10(9)/L were evaluated. At the start of the study, each of the 17 participating
      centers decided whether they would use a 10 x 10(9)/L prophylactic platelet
      transfusion trigger (group A/8 centers) or a 20 x 10(9)/L trigger (group B/9
      centers). Bleeding complications (World Health Organization grade 2-4) during
      treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A
      and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were
      generally not related to the patient's platelet count but were the consequence of
      local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty
      six percent of the serious bleeding episodes occurred during induction
      chemotherapy. No patient died of a bleeding complication. There were no
      significant differences in the number of red blood cell transfusions administered
      between the two groups, but there were significant differences in the number of
      platelet transfusions administered per treatment cycle: pooled random donor
      platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets
      averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This
      resulted in the cost of platelet therapy being one third lower in group A
      compared with group B without any associated increase in bleeding risk.

PMID- 9572995
TI  - A double-blind placebo-controlled trial of granulocyte colony-stimulating factor
      in elderly patients with previously untreated acute myeloid leukemia: a Southwest
      oncology group study (9031).
AB  - Older age is a poor prognosis factor in acute myeloid leukemia (AML). This double
      blind trial was designed to test the hypothesis that granulocyte colony
      stimulating factor (G-CSF) used as supportive care could improve the treatment of
      elderly AML patients. Two hundred thirty-four patients 55 or more years of age
      with a morphologic diagnosis of de novo or secondary AML, French-American-British
      (FAB) M0-M7, excluding M3, were randomly assigned to a standard induction regimen
      (daunorubicin at 45 mg/m2 intravenously [IV] on days 1 through 3 and Ara-C at 200
      mg/m2 IV continuous infusion on days 1 through 7) plus either placebo or G-CSF
      (400 microg/m2 IV over 30 minutes once daily). Results are reported here for 211
      centrally confirmed cases of non-M3 AML. The two groups were well balanced in
      demographic, clinical, and hematological parameters, with median ages of 68 years
      in the G-CSF and 67 years in the placebo groups. The complete response (CR) rate
      was not significantly better in the G-CSF group: 50% in the placebo and 41% in
      the G-CSF group (one-tailed P = .89). Median overall survival was also similar, 9
      months (95% confidence interval [CI], 7 to 10 months) in the placebo and 6 months
      (95% CI, 3 to 8 months) in the G-CSF arms (P = .71). We found a significant 15%
      reduction in the time to neutrophil recovery in the G-CSF group (P = .014). G-CSF
      had no impact on recovery from thrombocytopenia (P = .80) or duration of first
      hospitalization (P = .27). When infection complications were evaluated, G-CSF had
      a beneficial effect on the duration but not on incidence of infection. G-CSF
      patients had fewer days with fever and shorter duration of antibiotic use.
      However, there was no difference in the frequency of total documented infections
      or in the number of fatal infections (19% placebo v 20% G-CSF). In this study of
      elderly AML patients, G-CSF improved clinical parameters of duration of
      neutropenia and antibiotic use, but did not change CR rate or survival or shorten
      hospitalization.

PMID- 9572996
TI  - Clinical significance of HLA-DRB1*0410 in Japanese patients with idiopathic
      thrombocytopenic purpura.
AB  - We performed HLA-A, -B, and -C antigen and -DR DNA typing in 111 Japanese
      patients with idiopathic thrombocytopenic purpura (ITP). DRB1*0410 was
      significantly increased in ITP patients compared with healthy controls (relative
      risk = 9.52, P < .05), but the other DRB1*04 alleles showed no significant
      differences. On HLA-DR serotyping, patients with Vogt-Koyanagi-Harada disease
      (VKH) had a high frequency of DR4, so we compared the frequencies of DRB1*04
      suballeles between ITP and VKH. The high frequency of DRB1*04 was dependent on
      DRB1*0405 in VKH, but on DRB1*0410 in ITP. Plasma autoantibodies were studied in
      111 patients using a microtiter well assay. Thirty-six patients had anti
      GPIIb/IIIa autoantibodies, and antibody positivity was associated with HLA-DR4
      (29 of 36, 80.6% v 28 of 75, 37.3%) but not with DRB1*0410. When HLA-DR4 and
      DRB1*0410 were compared between patients with a good or poor response to
      prednisolone, HLA-DR4 was decreased and DRB1*0410 was significantly decreased
      (chi2 = 11.455, P < .01) in patients with a good response. In conclusion, this
      study showed that genetically determined factors influence the course of ITP.
      However, our findings should be considered preliminary because of possible racial
      differences in HLA status between Japanese and other ITP patients.

PMID- 9572997
TI  - Clinical significance of inhibitors in acquired von Willebrand syndrome.
AB  - Of 260 patients enrolled, 25 patients (9.6%) were associated with acquired von
      Willebrand syndrome (AvWS). We studied 25 patients with AvWS, retrospectively.
      AvWS was diagnosed by reduced levels of von Willebrand factor (vWF) (decrease of
      von Willebrand factor antigen [vWF:Ag] and von Willebrand ristocetin cofactor
      [vWF:RCoF]), a decrease of ristocetin-induced platelet agglutination (RIPA),
      sometimes decreased high-molecular-weight multimers, and prolonged bleeding time
      with neither prior nor family histories of bleeding problems and the evidence of
      normal vWF:RCoF in their families. The inhibitor of vWF was determined by mixing
      patient plasma with pooled normal plasma. Eight patients in this study had the
      inhibitors to vWF that were of the IgG class; the subclasses were IgG1 (7 cases)
      and IgG2 (1 case). Multimeric analysis of vWF showed selective loss of large
      multimers in most patients with AvWS similar to that of congenital type-2 von
      Willebrand disease (vWD). All inhibitors blocked ristocetin-mediated vWF binding
      to platelets. Five out of 6 IgGs evaluated here recognized the 39/34-kD fragment
      (residues 480/481-718) and Fragment III (residues 1-1365) that implied binding
      domain of glycoprotein Ib (GPIb), whereas 1 recognized Fragment I (residues 911
      1365). A close relationship was found between the presence of the inhibitor and
      bleeding tendency. Of the 7 patients with inhibitors, 6 patients (86%) had a
      bleeding tendency, as well as 1 of the 15 patients without inhibitors (6%). The
      efficacy of treatment of underlying diseases and/or therapy with deamino D
      arginine vasopressin (DDAVP) for the treatment of AvWS also depends on the
      presence of an inhibitor. Four of 8 patients with inhibitors (50%) had poor
      response to treatment of the underlying disease and/or therapy with DDAVP, as
      well as 1 of the 16 patients without inhibitors (6%). These results indicate that
      patients with AvWS developing inhibitors to vWF are likely to have bleeding
      problems and might be resistant to treatment of underlying diseases and/or
      therapy with DDAVP for bleeding to AvWS. We also showed evidence that intravenous
      immunoglobulin therapy (0.3 g/kg, 3 days) was effective to correct a hemostatic
      defect and manage severe bleeding in a patient with AvWS developing inhibitors.
      We might consider an additional treatment including expensive high-dose
      immunoglobulin therapy when uncontrollable bleeding is continued after the
      treatment of the underlying diseases and/or therapy with DDAVP.

PMID- 9572998
TI  - Splenectomy and risk of blast transformation in myelofibrosis with myeloid
      metaplasia. Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia.
AB  - An unexpectedly high incidence of blast transformation after splenectomy has been
      reported in patients with myelofibrosis with myeloid metaplasia. However, whether
      this was associated with spleen removal after adjustment for risk factors was not
      determined. We conducted a multicenter historical cohort study of patients with
      myelofibrosis with myeloid metaplasia diagnosed from January 1970 through January
      1994. A total of 549 patients (325 men and 224 women from 22 to 92 years of age;
      median age, 63 years) were included in the final data set. The Cox's proportional
      hazards model was used to identify factors associated with blast transformation
      and death. To further adjust for factors related to spleen removal assignment, a
      propensity score for splenectomy was estimated using recursive-partitioning
      analysis. Blast transformation developed in 78 patients (14.2%). Patients who
      underwent splenectomy developed more blast transformations than those who were
      not splenectomized (23 of 87 [26.4%] v 55 of 462 [11.9%]; P < .001). The
      cumulative incidence of blast transformation 12 years after diagnosis was 27.0%
      in nonsplenectomized patients and 55.0% in splenectomized ones (P = . 01). The
      risk factors independently predictive of blast transformation included prior
      splenectomy (relative risk = 2.61), platelet count less than 100 x 10(9)/L at
      diagnosis (relative risk = 2.45), and the presence of blasts in peripheral blood
      at diagnosis (relative risk = 2.31). The relative risk of blast transformation in
      splenectomized patients increased from 2.2 at 48 months from diagnosis to 14.3 at
      12 years. Patients with the same propensity score for splenectomy showed a higher
      risk for blast transformation on the basis of having undergone splenectomy (P =
      .02). In conclusion, the risk of blast transformation is significantly increased
      in subjects who underwent splenectomy and appears to be independent of factors
      related to spleen removal assignment.

PMID- 9572999
TI  - Long-term outcome after marrow transplantation for severe aplastic anemia.
AB  - We reviewed the records and reevaluated 212 patients with aplastic anemia
      transplanted at the Fred Hutchinson Cancer Research Center (FHCRC) between 1970
      and 1993 who survived >/=2 years and who have been followed for up to 26 years.
      Parameters analyzed included hematopoietic function, chronic graft-versus-host
      disease (GVHD), skin disease, cataracts, lung disease, skeletal problems,
      posttransplant malignancy, depression, pregnancy/fatherhood, and the return to
      work or school, as well as patient self-assessment of physical and psychosocial
      health, social interactions, memory and concentration, and overall severity of
      symptoms. Survival probabilities at 20 years were 89% for patients without (n =
      125) and 69% for patients with chronic GVHD (n = 86) (the status was uncertain in
      1 surviving patient). All patients had normal hematopoietic parameters. Skin
      problems occurred in 14%, cataracts in 12%, lung disease in 24%, and bone and
      joint problems in 18% of patients. Eleven patients (12%) developed a solid tumor
      malignancy and 19% of patients experienced depression. Chronic GVHD was the
      dominant risk factor for late complications. Seventeen patients died at 2.5 to
      20.4 years posttransplant; 13 of these had chronic GVHD and related
      complications. At 2 years, 83% of patients had returned to school or work; the
      proportion increased to 90% by 20 years. At least half of the patients preserved
      or regained the ability to become pregnant or father children. Patients rated
      their quality of life as excellent and symptoms as minimal or mild. In
      conclusion, marrow transplantation in patients with aplastic anemia established
      long-term normal hematopoiesis. No new hematologic disorders occurred. The major
      cause of morbidity and mortality was chronic GVHD. However, the majority of
      patients who survived beyond 2 years returned to a fully functional life.

PMID- 9573000
TI  - Long-term immune reconstitution and outcome after HLA-nonidentical T-cell
      depleted bone marrow transplantation for severe combined immunodeficiency: a
      European retrospective study of 116 patients.
AB  - We have performed a retrospective analysis of the development of T- and B-cell
      functions after HLA-nonidentical T-cell-depleted bone marrow transplantation
      (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at
      18 European centers between December 1982 and December 31, 1993. One hundred
      sixteen of 193 patients were alive with evidence of engraftment 6 months after
      BMT. Development of T-cell function occurred earlier than B-cell function and was
      achieved more frequently up to the time of last follow-up. The median time to
      achieve normal T-cell function was 8.7 months, whereas the median time to achieve
      normal B-cell function was 14.9 months. Twenty-four patients died later than 6
      months post-BMT, mainly due to chronic graft-versus-host disease (cGVHD) and/or
      viral infection. Absence of T-cell reconstitution 6 months after BMT, unlike
      absence of B-cell reconstitution, was associated with a poor outcome. Two
      additional factors were associated with a poor outcome: presence of cGVHD 6
      months after BMT and B- SCID versus B+ SCID. However, two of these three factors
      remained as significant prognostic factors in a multivariate analysis: the
      absence of T-cell function and the presence of cGVHD 6 months after BMT. Analysis
      of the factors influencing the development of immune reconstitution showed that T
      and B-cell functions occurred earlier and more frequently in B+ SCID versus B-
      SCID patients. Acute GVHD was associated with a slower development of T-cell
      function at 6 months, and cGVHD had a negative influence on the development of T
      cell function afterwards, but neither acute nor chronic GVHD was found to
      influence the development of B-cell function. Once engraftment occurred, whether
      patients had or had not received Busulfan in the conditioning regimen did not
      influence the kinetics and quality of T-cell function development. In a
      multivariate study, two factors were found to influence the T-cell function 6
      months after BMT: type of SCID and acute GVHD. The results of this retrospective
      analysis should lead to new protocols adapted to SCID disease, considering that
      disease-related as well as BMT-related parameters influence the development of
      immune function and thereby long-term outcome after HLA-nonidentical T-cell
      depleted BMT.

PMID- 9573001
TI  - Semiquantitative Epstein-Barr virus (EBV) polymerase chain reaction for the
      determination of patients at risk for EBV-induced lymphoproliferative disease
      after stem cell transplantation.
AB  - Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a serious and
      potentially fatal complication after allogeneic stem cell transplantation (SCT).
      To evaluate levels of EBV DNA in SCT patients, a semiquantitative polymerase
      chain reaction (PCR) assay was developed. DNA was extracted from peripheral blood
      leukocytes and diluted, and PCR was performed by using a primer set specific for
      a well-conserved sequence of the internal repeat 1 region of the EBV genome.
      Forty-one SCT patients were screened with this method. Thirty-seven patients
      received allogeneic transplants, of which 18 were T-cell-depleted marrow. Four
      additional patients received autologous SCT, one of which was T-cell depleted.
      The mean time of follow-up by EBV PCR was 147 days (range, 47 to 328 days)
      posttransplant. The range of EBV copies/microg DNA from normal EBV sero-positive
      donors was 40 to 4,000. Seven patients had >/=40,000 copies of EBV DNA/microg
      DNA, all of whom were recipients of T-cell-depleted SCT. Five of the seven
      patients with elevated levels of EBV DNA developed EBV-LPD. Four of these five
      patients with EBV-LPD had elevated levels of EBV DNA from 1 to 8 weeks before
      diagnosis. Two patients with EBV-LPD had normal levels of EBV DNA, and two
      patients with >/=40,000 copies EBV/microg DNA did not develop EBV-LPD. In one
      patient, clinical resolution of disease correlated with a decrease in EBV DNA and
      an increase in the level of EBV-specific cytotoxic T-cell precursors. These data
      indicate that the measurement of EBV viral load with semiquantitative PCR is
      useful in detecting EBV-LPD in high-risk patients before the onset of clinical
      symptoms. Because not all patients with elevated levels of EBV DNA develop EBV
      LPD, semiquantitative PCR results cannot substitute for clinical, radiographic,
      and pathological confirmation of this diagnosis.

PMID- 9573002
TI  - Dose-intensive melphalan with blood stem-cell support for the treatment of AL
      (amyloid light-chain) amyloidosis: survival and responses in 25 patients.
AB  - AL (amyloid light-chain) amyloidosis is an uncommon plasma cell disorder in which
      depositions of amyloid light-chain protein cause progressive organ failure and
      death in a median of 13 months. Autologous stem-cell transplantation is effective
      therapy for multiple myeloma and therefore, we evaluated its efficacy for AL
      amyloidosis. Patients with adequate cardiac, pulmonary, and renal function had
      stem cells mobilized with granulocyte-colony stimulating factor and were treated
      with dose-intensive intravenous melphalan (200 mg/m2). Response to therapy was
      determined by survival and improvement of performance status, complete response
      or persistence of the clonal plasma cell disorder, and change in the function of
      organs involved with amyloid at baseline. We enrolled 25 patients with a median
      age of 48 years (range, 29-60), all of whom had biopsy-proven amyloidosis with
      clonal plasma cell disorders. Twenty-two (88%) were Southwest Oncology Group
      performance status 1 or 2 within a year of diagnosis, and 16 (64%) had received
      no prior therapy. Predominant amyloid-related organ involvement was cardiac (n =
      8), renal (n = 7), hepatic (n = 6), neuropathic (n = 3), and lymphatic (n = 1).
      Fifteen patients had one or two organ systems involved, whereas 10 had three or
      more involved. With a median follow-up of 24 months (12-38), 17 of 25 patients
      (68%) are alive, and the median survival has not been reached. Thirteen of 21
      patients (62%) evaluated 3 months posttransplant had complete responses of their
      clonal plasma cell disorders. Currently, two thirds of the surviving patients (11
      of 17) have experienced improvements of amyloid-related organ involvement in all
      systems, whereas 4 of 17 have stable disease. The improvement in the median
      performance status of the 17 survivors at follow-up (0 [range, 0-3]) is
      statistically significant versus baseline (2 [range, 1-3]; P < . 01). Significant
      negative prognostic factors with respect to overall survival include amyloid
      involvement of more than two major organ systems and predominant cardiac
      involvement. Three patients have experienced relapses of the clonal plasma cell
      disorder at 12 and 24 months. Dose-intensive therapy should currently be
      considered as the preferred therapy for patients with AL amyloidosis who meet
      functional criteria for autologous transplantation.

PMID- 9573003
TI  - Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment
      of relapse after allogeneic bone marrow transplant.
AB  - Donor lymphocyte infusions (DLI) can induce remissions in patients who have
      relapsed after allogeneic bone marrow transplantation (BMT). However, DLI
      frequently also result in significant acute and/or chronic graft-versus-host
      disease (GVHD). Several clinical and experimental lines of evidence have
      suggested that CD8(+) T cells play a critical role in the pathogenesis of GVHD.
      To develop methods to reduce the incidence of GVHD associated with DLI, we
      administered defined numbers of CD4(+) donor T cells after ex vivo depletion of
      CD8(+) lymphocytes to 40 patients with relapsed hematologic malignancies after
      allogeneic BMT. Cohorts of patients received 0.3, 1.0, or 1.5 x 10(8) CD4(+)
      cells/kg. Overall, 12 of 38 patients (32%) evaluable for toxicity developed acute
      or chronic GVHD. However, 6 of 27 patients (22%) receiving 0.3 x 10(8) CD4
      cells/kg developed GVHD compared with 6 of 11 patients (55%) who received >/=1.0
      x 10(8) CD4 cells/kg (P = .07). Treatment-related mortality was low (3%), with 1
      death related to infection in the setting of immunosuppression for GVHD. Disease
      responses after CD4(+) DLI were documented in 15 of 19 patients (79%) with early
      phase chronic myelogenous leukemia (CML) relapse, 5 of 6 patients (83%) with
      relapsed multiple myeloma, and 1 patient with myelodysplasia. For patients with
      early-phase CML relapse, the Kaplan-Meier probability of achieving complete
      cytogenetic remission was 87% and the probability of complete molecular response
      was 78% at 1 year after DLI. The median time to complete cytogenetic response and
      molecular response in patients with CML was 13 weeks (range, 9 to 30 weeks) and
      34 weeks (range, 10 to 56 weeks), respectively. The median time to response in
      patients with multiple myeloma was 26 weeks (range, 15 to 62 weeks). All patients
      in this trial who developed GVHD demonstrated tumor regression, but the presence
      of GVHD was not required for patients to achieve a response, because 48% of
      responding patients never developed evidence of GVHD. Two patients with CML who
      did not respond at dose level 1 subsequently achieved complete cytogenetic
      remission after a second infusion of CD8-depleted cells at dose level 2. In
      patients with evidence of mixed hematopoietic chimerism who achieved a complete
      remission after DLI, cytogenetic analysis of marrow cells also demonstrated
      conversion to complete donor hematopoiesis in all evaluable patients. These
      studies suggest that relatively low numbers of CD8-depleted donor lymphocytes are
      effective in inducing complete remissions in patients with stable-phase CML and
      multiple myeloma who have relapsed after allogeneic BMT. Because of the
      relatively low risk of toxicity associated with the infusion of defined numbers
      of CD4(+) donor cells, further studies can be undertaken in the setting of
      persistent minimal residual disease to prevent relapse after allogeneic BMT.

PMID- 9573004
TI  - Lymphohematopoietic engraftment in minimally myeloablated hosts.
AB  - The concept that myeloablation to open space was a prerequisite for marrow stem
      cell engraftment has been challenged by studies showing high rates of engraftment
      in nonmyeloablated mice (Stewart et al, Blood 81:2566, 1993; Quesenberry et al,
      Blood Cells 20:97, 1994; Brecher et al, Blood Cells 5:237, 1979; Saxe et al, Exp
      Hematol 12:277, 1984; and Wu et al, Exp Hematol 21:251, 1993). However,
      relatively large numbers of marrow cells were necessary to achieve high long-term
      donor percentages. We have demonstrated, using a BALB/c male/female marrow
      transplant model and detecting male DNA in host tissues by Southern blot or
      fluorescent in situ hybridization, that exposure to doses of irradiation that
      cause minimal myeloablation (50 to 100 cGy) leads to very high levels of donor
      chimerism, such that relatively small numbers of marrow cells (10 to 40 million)
      can give donor chimerism in the 40% to 100% range. Studies of radiation
      sensitivity of long-term engrafting cells have shown that 100 cGy, although not
      myelotoxic, is stem cell toxic, and indicate that the final host:donor ratios are
      determined by competition between host and donor stem cells. These data indicate
      that low levels of irradiation should be an effective approach to nontoxic marrow
      transplantation in gene therapy or in attempts to create allochimerism to treat
      such diseases as cancer, sickle cell anemia, or thalassemia.

PMID- 9573005
TI  - Engraftment of cultured human hematopoietic cells in sheep.
AB  - In an effort to expand human hematopoietic progenitors and stem cells in vitro,
      we cultured human CD34(+)c-kitlow bone marrow cells in suspension in the presence
      of KIT ligand, FLK2/FLT3 ligand, interleukin-6 (IL-6), and erythropoietin with or
      without IL-3 and tested their engrafting capabilities by injecting them into
      sheep fetuses. As markers for engraftment, we analyzed CD45(+) cells and
      karyotypes of the colonies grown in methylcellulose culture. In three separate
      experiments, day-60 engraftment in the bone marrow was seen with both fresh cells
      and cells cultured in the presence or absence of IL-3. When fetuses were allowed
      to be born and analyzed for CD45(+) cells, no long-term engraftment was seen with
      cultured cells. We then pooled the CD45(+) cells of the fetal samples and
      transplanted them into secondary recipient fetuses. Day-60 engraftment in the
      secondary recipients was again noted when transplantation in the primary
      recipients was initiated with fresh cells. There were 3 cases in which cultured
      cells showed signs of engraftment in the secondary recipients, but the remaining
      24 cases showed no signs of engraftment. These data documented that suspension
      culture for 2 weeks of enriched adult human bone marrow cells can maintain short
      term (2 months) engrafting cells, but may not maintain longer term engrafting
      cells. This sheep/human xenograft model may serve as an excellent method for the
      evaluation of the engraftment potential of in vitro-expanded cells.

PMID- 9573006
TI  - Delayed targeting of cytokine-nonresponsive human bone marrow CD34(+) cells with
      retrovirus-mediated gene transfer enhances transduction efficiency and long-term
      expression of transduced genes.
AB  - Primitive hematopoietic progenitor cells (HPCs) are potential targets for
      treatment of numerous hematopoietic diseases using retroviral-mediated gene
      transfer (RMGT). To achieve high efficiency of gene transfer into primitive HPCs,
      a delicate balance between cellular activation and proliferation and maintenance
      of hematopoietic potential must be established. We have demonstrated that a
      subpopulation of human bone marrow (BM) CD34(+) cells, highly enriched for
      primitive HPCs, persists in culture in a mitotically quiescent state due to their
      cytokine-nonresponsive (CNR) nature, a characteristic that may prevent efficient
      RMGT of these cells. To evaluate and possibly circumvent this, we designed a two
      step transduction protocol using neoR-containing vectors coupled with flow
      cytometric cell sorting to isolate and examine transduction efficiency in
      different fractions of cultured CD34(+) cells. BM CD34(+) cells stained on day 0
      (d0) with the membrane dye PKH2 were prestimulated for 24 hours with stem cell
      factor (SCF), interleukin-3 (IL-3), and IL-6, and then transduced on fibronectin
      with the retroviral vector LNL6 on d1. On d5, half of the cultured cells were
      transduced with the retroviral vector G1Na and sorted on d6 into cytokine
      responsive (d6 CR) cells (detected via their loss of PKH2 fluorescence relative
      to d0 sample) and d6 CNR cells that had not divided since d0. The other half of
      the cultured cells were first sorted on d5 into d5 CR and d5 CNR cells and then
      infected separately with G1Na. Both sets of d5 and d6 CR and CNR cells were
      cultured in secondary long-term cultures (LTCs) and assayed weekly for transduced
      progenitor cells. Significantly higher numbers of G418-resistant colonies were
      produced in cultures initiated with d5 and d6 CNR cells compared with respective
      CR fractions (P < .05). At week 2, transduction efficiency was comparable between
      d5 and d6 transduced CR and CNR cells (P > .05). However, at weeks 3 and 4, d5
      and d6 CNR fractions generated significantly higher numbers of neoR progenitor
      cells relative to the respective CR fractions (P < .05), while no difference in
      transduction efficiency between d5 and d6 CNR cells could be demonstrated.
      Polymerase chain reaction (PCR) analysis of the origin of transduced neoR gene in
      clonogenic cells demonstrated that mature progenitors (CR fractions) contained
      predominantly LNL6 sequences, while more primitive progenitor cells (CNR
      fractions) were transduced with G1Na. These results demonstrate that prolonged
      stimulation of primitive HPCs is essential for achieving efficient RMGT into
      cells capable of sustaining long-term in vitro hematopoiesis. These findings may
      have significant implications for the development of clinical gene therapy
      protocols.

PMID- 9573007
TI  - Myeloid development is selectively disrupted in PU.1 null mice.
AB  - The ets family transcription factor PU.1 is expressed in monocytes/macrophages,
      neutrophils, mast cells, B cells, and early erythroblasts, but not in T cells. We
      have recently shown that PU.1 gene disruption results in mice with no detectable
      monocytes/macrophages and B cells but T-cell development is retained. Although
      neutrophil development occurred in these mice, it was delayed and markedly
      reduced. We now proceed to demonstrate that PU. 1 null hematopoietic cells fail
      to proliferate or form colonies in response to macrophage colony-stimulating
      factor (M-CSF), granulocyte CSF (G-CSF), and granulocyte/macrophage CSF (GM-CSF).
      In contrast, PU.1 null cells did proliferate and form colonies in response to
      interleukin-3 (IL-3), although the response was reduced as compared with control
      littermates. Compared with control cells, PU.1 null cells had minimal expression
      of G- and GM-CSF receptors and no detectable M-CSF receptors. The size of
      individual myeloid colonies produced from PU.1 null primitive and committed
      myeloid progenitors in the presence of IL-3, IL-6, and stem cell factor (SCF)
      were reduced compared with controls. Under these conditions, PU.1 null
      progenitors produced neutrophils but not monocytes/macrophages. These
      observations suggest that PU.1 gene disruption induces additional cell-autonomous
      effects that are independent of the alterations in myeloid growth factor receptor
      expression. Our results demonstrate that PU.1 gene disruption affects a number of
      developmentally regulated hematopoietic processes that can, at least in part,
      explain the changes in myeloid development and reduction in myeloid and
      neutrophil expansion observed in PU.1 null mice.

PMID- 9573008
TI  - Endomitosis of human megakaryocytes are due to abortive mitosis.
AB  - During megakaryocyte differentiation, the promegakaryoblast (immature
      megakaryocyte) increases its ploidy to a 2(x) DNA content by a poorly understood
      process called endomitosis. This leads to the formation of a giant cell, the
      megakaryocyte (MK), which subsequently gives rise to platelets. In this report,
      we show that endomitosis of human MKs is due to abortive mitosis. Human MKs were
      obtained by a two-step purification of CD34(+) blood or marrow precursors
      followed by in vitro culture in the presence of MK growth factors. Microscopic
      examination shows that a large number of centrosomes (up to 32) and centrioles
      are present in polyploid MKs. After nocodazole treatment, more than 20% of the MK
      are blocked in a typical pseudo-metaphase. Both spontaneous and nocodazole
      induced endomitosis are associated with a breakdown of the nuclear envelope and
      possess a complex mitotic spindle composed of several asters. Spindle
      microtubules radiate from each aster, creating a spherical structure. At
      metaphase, expression of the kinetochore phosphoepitope recognized by the 3F3/2
      antibody is lost, and the sister chromatids segregate moving toward the spindle
      poles. After limited segregation, the chromosomes decondense and the nuclear
      envelope reforms in the absence of cytokinesis, isolating all chromosomes in a
      single nucleus. It has been proposed that endomitosis could be due to an abnormal
      CDK1 activity or an absence of cyclin B1. Our results show that cyclin B1 can be
      detected in all MKs, including those with a ploidy of 8N or more. The cyclin B1
      staining colocalizes with the mitotic spindle. Using flow cytometry, the level of
      cyclin B1 increased until 8N, but remained identical in 16N and 32N MKs. Cell
      sorting was used to separate the MKs into a 2N/4N and >4N population. Both cyclin
      B1 and CDK1 could be detected in the endomitotic polyploid MKs using Western blot
      analysis, and a histone H1 kinase activity was associated with immunoprecipitated
      cyclin B1. We conclude that endomitosis of human MKs is due to abortive mitosis,
      possibly due to alterations in the regulation of mitotic exit.

PMID- 9573009
TI  - Human CD34(+) bone marrow cells regulate stromal production of interleukin-6 and
      granulocyte colony-stimulating factor and increase the colony-stimulating
      activity of stroma.
AB  - Cytokines produced by stromal cells induce the proliferation and differentiation
      of hematopoietic cells in the marrow microenvironment. We hypothesized that cross
      talk between hematopoietic cells at different stages of differentiation and
      stromal cells influences stromal cytokine production and is responsible for
      maintaining steady-state hematopoiesis and responding to stress situations. We
      show that coculture of primitive CD34(+) cells in contact with or separated by a
      transwell membrane from irradiated human bone marrow stromal layers induces a
      fourfold to fivefold increase in interleukin-6 (IL-6) and granulocyte colony
      stimulating factor (G-CSF) levels in the stromal supernatant (SN) during the
      first week. Levels of both cytokines decreased to baseline after coculture of
      CD34(+) cells for 3 to 5 weeks. Coculture of more mature CD15(+)/CD14(-) myeloid
      precursors induced only a transient 1.5- to 2-fold increase in IL-6 and G-CSF at
      48 hours. Neither CD34(+) nor CD15(+)/CD14(-) cells produced IL-6, G-CSF, IL
      1beta, or tumor necrosis factor alpha. When CD34(+) cells were cultured in
      methylcellulose medium supplemented with cytokines at concentrations found in
      stromal SN or supplemented with stromal SN, a fourfold to fivefold increase in
      colony formation was seen over cultures supplemented with erythropoietin (EPO)
      only. When cultures were supplemented with the increased concentrations of IL-6
      and G-CSF detected in cocultures of stroma and CD34(+) cells or when CD34(+)
      cells were cocultured in methylcellulose medium in a transwell above a stromal
      layer, a further increase in the number and size of colonies was seen. The colony
      forming unit-granulocyte-macrophage-stimulating activity of stromal SN was
      neutralized by antibodies against G-CSF or IL-6. These studies indicate that
      primitive CD34(+) progenitors provide a soluble positive feedback signal to
      induce cytokine production by stromal cells and that the observed increase in
      cytokine levels is biologically relevant.

PMID- 9573010
TI  - Lyn physically associates with the erythropoietin receptor and may play a role in
      activation of the Stat5 pathway.
AB  - Protein tyrosine phosphorylation plays a crucial role in signaling from the
      receptor for erythropoietin (Epo), although the Epo receptor (EpoR) lacks the
      tyrosine kinase domain. We have previously shown that the Jak2 tyrosine kinase
      couples with the EpoR to transduce a growth signal. In the present study, we
      demonstrate that Lyn, a Src family tyrosine kinase, physically associates with
      the EpoR in Epo-dependent hematopoietic cell lines, 32D/EpoR-Wt and F36E.
      Coexpression experiments in COS7 cells further showed that Lyn induces tyrosine
      phosphorylation of the EpoR and that both LynA and LynB, alternatively spliced
      forms of Lyn, bind with the membrane-proximal 91-amino acid region of the EpoR
      cytoplasmic domain. In vitro binding studies using GST-Lyn fusion proteins
      further showed that the Src homology (SH)-2 domain of Lyn specifically binds with
      the tyrosine-phosphorylated EpoR in lysate from Epo-stimulated cells, whereas the
      tyrosine kinase domain of Lyn binds with the unphosphorylated EpoR. Far-Western
      blotting and synthetic phosphopeptide competition assays further indicated that
      the Lyn SH2 domain directly binds to the tyrosine-phosphorylated EpoR, most
      likely through its interaction with phosphorylated Y-464 or Y-479 in the carboxy
      terminal region of the EpoR. In vitro binding studies also demonstrated that the
      Lyn SH2 domain directly binds to tyrosine-phosphorylated Jak2. In vitro
      reconstitution experiments in COS7 cells further showed that Lyn induces tyrosine
      phosphorylation of Stat5, mainly on Y-694, and activates the DNA-binding and
      transcription-activating abilities of Stat5. In agreement with this, Lyn enhanced
      the Stat5-dependent transcriptional activation when overexpressed in 32D/EpoR-Wt
      cells. In addition, Lyn was demonstrated to phosphorylate the EpoR and Stat5 on
      tyrosines in vitro. These results suggest that Lyn may play a role in activation
      of the Jak2/Stat5 and other signaling pathways by the EpoR.

PMID- 9573011
TI  - SHP-1 phosphatase C-terminus interacts with novel substrates p32/p30 during
      erythropoietin and interleukin-3 mitogenic responses.
AB  - SHP-1 protein tyrosine phosphatase is a critical negative regulator of mitogenic
      signaling, as demonstrated by the heightened growth responses to hematopoietic
      growth factors in hematopoietic cells of motheaten mice, which lack functional
      SHP-1 expression due to mutations in the SHP-1 gene. The mitogenic signaling
      molecules dephosphorylated by SHP-1 have not been fully identified. We detected
      two proteins (p32/p30) that are hyperphosphorylated in a DA3/erythropoietin
      receptor (EpoR) cell line that expresses a mutant containing the SHP-1 C-terminus
      that suppresses the function of the endogenous phosphatase and induces
      hyperproliferative responses to interleukin-3 (IL-3) and Epo. Hyperphosphorylated
      p32/p30 are also detected in motheaten hematopoietic cells, demonstrating an
      association of p32/p30 hyperphosphorylation with SHP-1-deficiency and growth
      factor-hyperresponsiveness. The hyperphosphorylated p32/30 associate with SHP-1
      via its C-terminus, because they coimmunoprecipitate with the phosphatase and the
      C-terminal mutant and they bind in vitro to a synthetic peptide of the mutant but
      not the GST fusion proteins of SHP-1 SH2 domains. Induction of p32/p30
      phosphorylation by IL-3 or Epo occurs mainly at 2 to 18 hours poststimulation in
      the DA3/EpoR cell line, indicating p32/p30 as novel signaling molecules during
      cell cycle progression. These data demonstrate a function for the SHP-1 C
      terminus in recruiting potential substrates p32/p30 and suggest that SHP-1 may
      regulates mitogenic signaling by dephosphorylating p32/p30.

PMID- 9573012
TI  - Enhanced megakaryocyte and erythroid development from normal human CD34(+) cells:
      consequence of enforced expression of SCL.
AB  - The product of the SCL gene is a basic helix-loop-helix (bHLH) transcription
      factor that is essential for the development of hematopoietic stem cells in both
      the embryo and the adult. However, once the stem cell compartment is established,
      the function of SCL in subsequent differentiation and commitment events within
      normal hematopoietic cells remains undefined. The aim of the current study was to
      investigate this role using purified normal human hematopoietic CD34(+) cells. An
      SCL retrovirus was used to transduce CD34(+) cells isolated from human bone
      marrow, peripheral blood, and umbilical cord blood. Enforced expression of SCL
      increased by a median of twofold the number of erythroid colonies, with an
      increase in both colony size and the rate of hemoglobinization. Unexpectedly,
      enforced expression in CD34(+) cells also significantly increased the number of
      megakaryocyte colonies, but with no impact on the size of colonies. There was no
      consistent effect on the number nor size of granulocyte-macrophage (GM) colonies.
      The proliferative effect of enforced SCL expression on erythroid cells was
      attributed to a shortened cell cycle time; the self-renewal capacity of erythroid
      or GM progenitors was unchanged, as was survival of cells within colonies. These
      results demonstrate a role for SCL in determining erythroid and megakaryocyte
      differentiation from normal human hematopoietic CD34(+) cells.

PMID- 9573013
TI  - Human hematopoietic progenitors express erythropoietin.
AB  - Erythropoietin (EPO) is a factor essential for erythroid cell proliferation,
      differentiation, and survival. The production of EPO by the kidneys in response
      to hypoxia and anemia is well documented. To determine whether EPO is also
      produced by hematopoietic cells, we analyzed the expression of EPO in normal
      human hematopoietic progenitors and in their progeny. Undifferentiated CD34(+)lin
      hematopoietic progenitors do not have detectable EPO mRNA. Differentiating
      CD34(+) cells that are stimulated with recombinant human EPO in serum-free liquid
      cultures express both EPO and EPO receptor (EPOR). Because CD34(+) cells
      represent a heterogeneous cell population, we analyzed individual burst-forming
      units-erythroid (BFU-E) and nonerythroid colony-forming unit-granulocyte
      macrophage colonies for EPO mRNA. Only BFU-E colonies were positive for EPO mRNA.
      Lysates from pooled BFU-E colonies stained positively for EPO by immunoblotting.
      To further confirm the intrinsic nature of erythroid EPO, we replaced extrinsic
      EPO in erythroid colony cultures with EPO-mimicking peptide (EMP). We show EPO
      expression in the EMP-stimulated BFU-Es at both mRNA and protein levels.
      Stimulation of bone marrow mononuclear cells (BMMCs) with EMP upregulated EPO
      expression. Furthermore, we found EPO and EPOR mRNAs as well as EPO protein in
      K562 cells, a human erythroleukemia cell line. Stimulation of K562 cells with EMP
      upregulated EPO expression. We suggest that EPO of erythroid origin may have a
      role in the regulation of erythropoiesis.

PMID- 9573014
TI  - The effects of colony-stimulating factor-1 on the distribution of mononuclear
      phagocytes in the developing osteopetrotic mouse.
AB  - Colony-stimulating factor-1 (CSF-1), the primary regulator of mononuclear
      phagocyte (Mphi) production, exists as either a circulating or cell surface,
      membrane-spanning molecule. To establish transplacental transfer of maternal CSF
      1, gestational day-17 mothers were injected intravenously with 125I-mouse CSF-1
      or human rCSF-1, and the 125I-cpm or human CSF-1 concentrations were measured in
      fetal tissue, placenta, and fetal/maternal sera. Biologically active CSF-1
      crossed the placenta and peaked in fetal tissue, placenta, and serum 10 minutes
      after injection. The role of CSF-1 in perinatal Mphi development was examined by
      studying the CSF-1-deficient osteopetrotic (csfmop/csfmop) mouse. Fetal/neonatal
      mice, derived from matings of either +/csfmop females with csfmop/csfmop males or
      the reciprocal pairings, were genotyped and tissue Mphi identified and
      quantified. In the presence of circulating maternal CSF-1 (+/csfmop mother), Mphi
      development in csfmop/csfmop liver was essentially complete at birth relative to
      +/csfmop littermates, but significantly reduced in spleen, kidney, and lung. In
      the absence of circulating maternal CSF-1 (csfmop/csfmop mother), Mphi numbers at
      birth were reduced in csfmop/csfmop liver relative to the offspring of +/csfmop
      mothers, but were similar in spleen, kidney, and lung. We conclude that CSF-1 is
      required for the perinatal development of most Mphi in these tissues.
      Compensation for total absence of local CSF-1 production by circulating, maternal
      CSF-1 is tissue-specific and most prominent in liver, the first fetal organ
      perfused by placental blood. However, because some Mphi developed in the complete
      absence of CSF-1, other factors must also be involved in the regulation of
      macrophage development.

PMID- 9573015
TI  - The carboxyl-terminal region of protein C is essential for its secretion.
AB  - We have previously reported a mutated protein C, designated protein C Nagoya
      (PCN), characterized by the deletion of a single guanine residue (8857G). This
      frameshift mutation results in the replacement of the carboxyl-terminal 39 amino
      acids of wild-type protein C (G381-P419) by 81 abnormal amino acids. This
      elongated mutant was not effectively secreted, and was retained in the
      endoplasmic reticulum. To determine why PCN is not secreted, we constructed a
      series of mutants from which some or all of the 81 amino acids were deleted. None
      of these shortened proteins were secreted from producing cells, indicating that
      the carboxyl-terminal extension is not mainly responsible for the intracellular
      retention of PCN, and that the 39 carboxyl-terminal amino acids of wild-type
      protein C are required for secretion. To determine which residues are essential
      for the secretion of protein C, deletion mutants of the carboxyl-terminal region
      (D401-P419) were prepared. Metabolic labeling showed that mutants of protein C
      truncated before W417, Q414, E411, or K410 were efficiently secreted. On the
      other hand, the mutants truncated before D409 were retained and degraded
      intracellularly. Immunofluorescence and immunoelectron microscopy showed that
      truncation before D409 blocks the movement from rough endoplasmic reticulum to
      the Golgi apparatus. To understand the conformational change in the carboxyl
      terminal region, two models of truncated activated protein C were constructed
      using energy optimization and molecular dynamics with water molecules.

PMID- 9573016
TI  - Platelet aggregation induced by a monoclonal antibody to the A1 domain of von
      Willebrand factor.
AB  - Shear-induced platelet aggregation (SIPA) involves von Willebrand Factor (vWF)
      binding to platelet glycoprotein (GP)Ib at high shear stress, followed by the
      activation of alphaIIb beta3. The purpose of this study was to determine the vWF
      sequences involved in SIPA by using monoclonal antibodies (MoAbs) to vWF known to
      interfere with its binding to GPIb and to alphaIIb beta3. Washed platelets were
      exposed to shear rates between 100 and 4,000 seconds-1 in a rotational
      viscometer. SIPA was quantitated by flow cytometry as the disappearance of single
      platelets (DSP) in the sheared sample in the presence of vWF, relative to a
      control in the absence of shear and vWF. At a shear rate of 4,000 seconds-1, DSP
      was increased from 5.9% +/- 3.5% in the absence of vWF to 32.7% +/- 6.3% in the
      presence of vWF. This increase in SIPA was not associated with an elevation of P
      selectin expression. vWF-dependent SIPA was completely abolished by MoAb 6D1 to
      GPIb and partially inhibited by MoAb 10E5 to alphaIIb beta3. Three MoAbs to vWF
      were compared for their effect on SIPA at 4,000 seconds-1 in the presence of vWF:
      MoAb 328, known to block vWF binding to GPIb in the presence of ristocetin, MoAb
      724 blocking vWF binding to GPIb in the presence of botrocetin, and MoAb 9, an
      inhibitor of vWF binding to alphaIIbbeta3. Similar to the effect of MoAb 6D1,
      MoAb 328 completely inhibited the effect of vWF, whereas MoAb 9 had a partial
      inhibitory effect, as MoAb 10E5 did. In contrast, MoAb 724, as well as its
      F(ab')2 fragments, promoted shear-dependent platelet aggregation (165% of the DSP
      value obtained in the absence of MoAb 724), indicating that MoAb 724 was
      responsible for an enhanced aggregation, which was independent of binding to the
      platelet Fcgamma receptor. In addition, the enhancement of aggregation induced by
      MoAb 724 was abrogated by MoAb 6D1 or 10E5 to the level of SIPA obtained in the
      presence of vWF incubated with a control MoAb to vWF. Finally, the activating
      effect of MoAb 724 was also found under static conditions at ristocetin
      concentrations too low to induce platelet aggregation. Our results suggested that
      on binding to a botrocetin-binding site on vWF, MoAb 724 mimics the effect of
      botrocetin by inducing an active conformation of vWF that is more sensitive to
      shear stress or to low ristocetin concentration.

PMID- 9573017
TI  - Tissue-specific expression of functional platelet factor XI is independent of
      plasma factor XI expression.
AB  - Platelet factor XI is an alternatively spliced product of the factor XI gene
      expressed specifically within megakaryocytes and platelets as an approximately
      1.9-kb mRNA transcript (compared with approximately 2.1 kb in liver cells)
      lacking exon V. Flow cytometry with an affinity-purified factor XI antibody, with
      PAC1 antibody (to the GPIIb/IIIa complex on activated platelets), and with S12
      antibody (to P-selectin, an alpha-granule membrane protein expressed on the
      platelet surface during secretion) on platelets activated with ADP, thrombin,
      thrombin receptor peptide (SFLLRN amide), or collagen at various concentrations
      exposed platelet factor XI and PAC1 antibody binding in parallel. Unactivated
      platelets expressed approximately 40% of total platelet factor XI but no PAC1
      binding sites. Enhanced membrane exposure of platelet factor XI is independent of
      alpha-granule secretion, because ADP and collagen exposed platelet factor XI but
      no S12 binding sites. Platelets from four patients with plasma factor XI
      deficiency (<0.04 U/mL) had normal constitutive and activation-dependent
      expression of platelet factor XI. Well-washed platelets from normal and from
      factor XI-deficient donors incubated with low concentrations of thrombin (0. 05
      to 0.1 U/mL) corrected the clotting defect observed with factor XI-deficient
      plasma. Thus, functionally active platelet factor XI is differentially expressed
      on platelet membranes in a tissue-specific manner both constitutively and in a
      concentration-dependent fashion by various agonists in the absence of detectable
      plasma factor XI.

PMID- 9573018
TI  - Simple collagen-like peptides support platelet adhesion under static but not
      under flow conditions: interaction via alpha2 beta1 and von Willebrand factor
      with specific sequences in native collagen is a requirement to resist shear
      forces.
AB  - The aim of this study was to define the need for specific collagen sequences and
      the role of their conformation in platelet adhesion to collagen under both static
      and flow conditions. We recently reported that simple triple-helical collagen
      related peptides (CRPs), GCP*(GPP*)10GCP*G and GKP*(GPP*)10GKP*G (single-letter
      amino acid code, P* = hydroxyproline; Morton et al, Biochem J 306:337, 1995) were
      potent stimulators of platelet activation and were able to support the adhesion
      of gel-filtered platelets examined under static conditions. The present study
      investigated whether these same peptides were able to support platelet adhesion
      under more physiologic conditions by examining static adhesion with platelet-rich
      plasma (PRP) and adhesion under flow conditions. In the static adhesion assay, we
      observed 20% surface coverage with platelet aggregates. In marked contrast, there
      was a total lack of adhesion under flow conditions examined at shear rates of 50
      and 300 s-1. Thus, the interaction of platelets with the CRPs is a low-affinity
      interaction unable on its own to withstand shear forces. However, the addition of
      CRPs to whole blood, in the presence of 200 micromol/L D-arginyl-glycyl-L
      aspartyl-L-tryptophan (dRGDW) to prevent platelet aggregation, caused an
      inhibition of about 50% of platelet adhesion to collagens I and III under flow.
      These results suggest that the collagen triple helix per se, as defined by these
      simple collagen sequences, plays an important contributory role in the overall
      process of adhesion to collagen under flow. The monoclonal antibody (MoAb) 176D7,
      directed against the alpha2 subunit of the integrin alpha2 beta1, was found to
      inhibit static platelet adhesion to monomeric but not fibrillar collagens I and
      III. However, under flow conditions, anti-alpha2 MoAbs (176D7 anf 6F1) inhibited
      adhesion to both monomeric and fibrillar collagens, indicating that alpha2 beta1
      is essential for adhesion to collagen under flow, independent of collagen
      conformation, whether monomeric or polymeric. To obtain further insight into the
      nature of the different adhesive properties of CRPs and native collagen, we
      investigated the relative importance of von Willebrand factor (vWF) and the
      integrin alpha2 beta1 in platelet adhesion to collagen types I and III, using the
      same shear rate (300 s-1) as used when testing CRPs under flow conditions. Our
      results, together with recent data of others, support a two-step mechanism of
      platelet interaction with collagen under flow conditions. The first step involves
      adhesion via both the indirect interaction of platelet glycoprotein (GP) Ib with
      collagen mediated by vWF binding to specific vWF-recognition sites in collagen
      and the direct interaction between platelet alpha2 beta1 and specific alpha2
      beta1-recognition sites in collagen. This suffices to hold platelets at the
      collagen surface. The second step occurs via another collagen receptor (thought
      to be GPVI) that binds to simple collagen sequences, required essentially to
      delineate the collagen triple helix. Recognition of the triple helix leads to
      strengthening of attachment and platelet activation.

PMID- 9573019
TI  - Effect of L-carnitine on human immunodeficiency virus-1 infection-associated
      apoptosis: a pilot study.
AB  - The Fas/Fas ligand system is involved in uncontrolled apoptosis, which ultimately
      leads to the loss of T lymphocytes in human immunodeficiency virus (HIV)-infected
      individuals. The signal transduced by Fas receptor involves the activation of an
      acidic sphingomyelinase, sphingomyelin breakdown, and ceramide production. Our
      recent reports have shown that L-carnitine inhibits Fas-induced apoptosis and
      ceramide production both in vitro and in vivo. The aim of this study was to
      study, in a preliminary fashion, the impact of long-term L-carnitine
      administration on CD4 and CD8 absolute counts, rate, and apoptosis in HIV-1
      infected subjects. The generation of cell-associated ceramide and HIV-1 viremia
      was also investigated. Eleven, asymptomatic, HIV-1-infected subjects, who refused
      any antiretroviral treatment despite experiencing a progressive decline of CD4
      counts, were treated with daily infusions of L-carnitine (6 g) for 4 months.
      Immunologic and virologic measures and safety were monitored at the start of the
      treatment and then on days 15, 30, 90, and 150. L-carnitine therapy resulted in
      an increase of absolute CD4 counts, which was statistically significant on day 90
      and 150 (P = . 010 and P = .019, respectively). A positive, not significant trend
      was also observed even in the change in absolute counts of CD8 lymphocytes. L
      carnitine therapy also led to a drop in the frequency of apoptotic CD4 and CD8
      lymphocytes. This reduction occurred gradually, but changes in actual values
      between each time point and baseline were strongly significant (P = .001 at the
      end of the study compared with the baseline). A strong reduction (P = .001) in
      cell-associated ceramide levels was found at the end of the study. In general,
      HIV-1 viremia increased slightly. No toxicity related to L-carnitine therapy was
      observed and dose reductions were not necessary. In HIV-1-infected subjects, long
      term infusions of L-carnitine produced substantial increases in the rate and
      absolute counts of CD4 and, to a lesser degree, of CD8 lymphocytes. This was
      paralleled by a reduced frequency of apoptotic cells of both subgroups and a
      decline in the levels of ceramide. No clinically relevant change of HIV-1 viremia
      was observed.

PMID- 9573020
TI  - Demonstration of Kaposi's sarcoma-associated herpes virus cyclin D homolog in
      cutaneous Kaposi's sarcoma by colorimetric in situ hybridization using a
      catalyzed signal amplification system.
AB  - Kaposi's sarcoma-associated herpes virus (KSHV)/human herpes virus 8 (HHV8) DNA
      sequences have been demonstrated in Kaposi's sarcoma (KS), as well as in some
      acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (NHL)
      and in multicentric Castleman's disease. Although KSHV DNA generally is abundant
      in KSHV-associated lymphomas, few copies of the virus are present in KS, a
      property that confounds detection by in situ methods. Previous in situ studies,
      which identified KSHV in lesions of KS, relied on the use of polymerase chain
      reaction (PCR) to amplify target DNA sequences before in situ hybridization (ISH)
      for localization or used ISH with radioactively-labeled probes to obtain adequate
      levels of detection sensitivity. In this study, a novel nonisotopic nucleic acid
      ISH method using catalyzed signal amplification and colorimetric detection
      without PCR-dependent target amplification was used to identify KSHV-specific
      sequences. The level of sensitivity was increased further by using a probe that
      detects viral cyclin D homolog transcripts, which are expressed at significant
      levels during latent viral infection. Thirty cutaneous lesions of KS (25 AIDS
      related and five classical European type) were evaluated. AIDS-related NHL and
      cell lines derived from patients with AIDS-related NHL, all of which were known
      to harbor KSHV by Southern blot analysis, were used as positive controls. NHL and
      benign cutaneous vascular lesions not associated with AIDS were used as negative
      controls. For each of the 30 KS lesions studied, hybridization signals were
      detected in most of the spindle cells surrounding the atypical slit-like vascular
      channels and also were detected in some endothelial cells in well-formed blood
      vessels in the perilesional dermis. Plaque and nodular lesions generally
      contained more labeled cells than did early patch lesions. All AIDS-related NHL
      and cell lines contained KSHV-specific sequences; however, the non-AIDS-related
      NHLs and benign vascular lesions were negative. These results confirm the
      presence of KSHV sequences in cutaneous KS and provide in situ evidence of
      infection by this virus in early patch-stage lesions. This study also defines the
      in situ expression of the KSHV cyclin D homolog viral oncogene in cutaneous KS.
      The use of this sensitive nonisotopic ISH method should allow detection of other
      KSHV-specific gene products, further defining the pathobiology of this virus.

PMID- 9573021
TI  - Novel evidence of expression and activity of ecto-phospholipase C gamma1 in human
      T lymphocytes.
AB  - Although much is known about the intracellular phospholipase C (PLC) specific for
      inositol phospholipids, few data are available about the presence of a less
      common PLC at the external side of the membrane bilayer of some cell types. This
      ectoenzyme seems to play particular roles in cellular function by hydrolyzing
      inositol lipids located on the outer leaflet of the plasma membrane. Here, we
      provide the first evidence that peripheral T lymphocytes express a discrete level
      of a PLCgamma1 at the outer leaflet of the plasma membrane. Flow cytometry showed
      that the PLCgamma1-positive (PLCgamma1(+)) cells (approximately 37%) were CD8(+)
      and CD45RA+. Biochemical evidence indicated that (1) this ectoenzyme displays a
      mass similar to the cytoplasmic form, (2) it is phosphorylated on tyrosine
      residues, and (3) its activity is Ca2+-dependent. In addition, this enzyme
      appeared to be correlated with the proliferative state of the cell, since
      stimulation with phytohemagglutinin (PHA) downregulated both its expression and
      activity, which were restored by treatment with an antiproliferative agent like
      natural interferon beta. Moreover, the different kinetics of formation of its
      hydrolytic products, inositol 1 phosphate and inositol 1:2 cyclic phosphate
      (Ins(1)P and Ins(1:2 cycl)P), formed upon incubation of the lymphocytes with [3H]
      lyso-phosphatidylinositol (PI), allow the hypothesis of a selective involvement
      of the two inositol phosphates in the mechanisms regulating the metabolism of
      particular T-lymphocyte subsets.

PMID- 9573022
TI  - In vivo tropism of hepatitis C virus genomic sequences in hematopoietic cells:
      influence of viral load, viral genotype, and cell phenotype.
AB  - Extrahepatic sites capable of supporting hepatitis C virus (HCV) replication have
      been suggested. We analyzed the influence of virological factors such as viral
      genotype and viral load, and cellular factors such as cell phenotype, on the
      detection rate of HCV sequences in hematopoietic cells of infected patients.
      Thirty-eight chronically infected patients were included in the study: 19
      infected by genotype 1 isolates (1a and 1b), 13 by nongenotype 1 isolates
      (including genotypes 2 a/c, 3a, and 4), and 6 coinfected by genotype 1 and 6
      isolates. Polymerase chain reaction (PCR) detection efficiency of viral genomic
      sequences, both the positive and negative strand RNA, was evaluated using RNA
      transcripts derived from genotype 1, 2, 3, and 4 cloned sequences and found to be
      equivalent within one log unit. The serum viral load, ranging from less than 2 x
      10(5) Eq/mL to 161 x 10(5) Eq/mL, did not influence the detection rate of either
      strand of RNA in patients' peripheral blood mononuclear cells (PBMCs). Positive
      and negative strand RNA were found in PBMCs of all 3 cohorts of patients with a
      detection rate ranging from 15% to 100% and from 8% to 83.3% for the positive and
      negative strand RNA, respectively. Coinfected patients showed a detection rate in
      all cases greater than 80%. Patients infected with genotype 1 isolates showed a
      higher detection rate of either strands of RNA when compared with patients
      infected with other genotypes (P <.001 and P <.04). Both strands were found
      restricted to polymorphonuclear leukocytes, monocytes/macrophages, and B (but not
      T) lymphocytes. These data show that HCV genomic sequences, possibly reflecting
      viral replication, can be detected in PBMCs of chronically infected patients
      independent of the viral load and that specific associated cell subsets are
      implicated in the harboring of such sequences.

PMID- 9573023
TI  - Stable transduction of the interleukin-2 gene into human natural killer cell
      lines and their phenotypic and functional characterization in vitro and in vivo.
AB  - A variety of strategies have been attempted in the past to stably transduce
      natural killer (NK) cells with cytokine or other cellular genes. Here, we
      demonstrate the successful delivery of the interleukin-2 (IL-2) gene into two
      human NK cell lines, IL-2-dependent NK-92 and IL-2-independent YT, by retroviral
      transduction. An MuLV-based retroviral vector expressing human IL-2 and neor
      markers from a polycistronic message was constructed and transduced into a CRIP
      packaging cell line. By coincubation of NK cells with monolayers of CRIP cells or
      by using retrovirus-containing supernatants in a flow-through method, 10% to 20%
      of NK cells were stably transduced. Upon selection in the presence of increasing
      G418 concentrations, transduced NK cells were able to proliferate independently
      of IL-2 for more than 5 months and to secrete up to 5.5 ng/10(6) cells/24 h of IL
      2. IL-2 gene-transduced NK-92 cells had an in vitro cytotoxicity against tumor
      targets that was significantly higher than that of parental cells and secreted
      interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) in
      addition to IL-2. Moreover, the in vivo antitumor activity of IL-2 gene
      transduced NK-92 cells against established 3-day liver metastases in mice was
      greater than that of parental nontransduced NK cells. Stable expression of the IL
      2 transgene in NK cells improved their therapeutic potential in tumor-bearing
      hosts. Thus, transduced NK cells secreted sufficient quantities of bioactive IL-2
      to proliferate in vitro and mediated the antitumor effects both in vitro and in
      vivo in the absence of exogenous IL-2. These results suggest that genetic
      modification of NK cells ex vivo could be useful for clinical cancer therapy in
      the future.

PMID- 9573024
TI  - Biologically active Fas antigen and its cognate ligand are expressed on plasma
      membrane-derived extracellular vesicles.
AB  - Exfoliation of plasma membrane components is a directed process that consumes
      energy and requires active cell metabolism. Proteins involved in regulating the
      survival and proliferation of eukaryotic cells are released on exfoliated
      vesicles. We examine here whether the Fas receptor and its cognate ligand (FasL)
      are present on vesicles shed from high metastatic potential CX-1 cells and low
      metastatic potential MIP-101 cells and from HuT 78 cells, respectively. Rates of
      exfoliation at 2 hours and cumulative levels of extracellular vesicles in serum
      free medium conditioned by CX-1 cells are increased by 1.8-fold and 1.6-fold,
      respectively, relative to that in medium conditioned by MIP-101 cells. Although
      vesicles shed from both cancer cell lines contain Fas antigen, the amount of Fas
      per vesicle and the percentage of vesicles containing Fas are increased for
      vesicles isolated from MIP-101 cells, relative to those from CX-1 cells, as
      determined by immunogold particle labeling and electron microscopy and by
      immunofluorescence microscopy and flow cytometry. Results of metabolic labeling
      with 35S-methionine indicate that Fas biosynthesis is reduced by up to 3.3-fold
      for CX-1 cells, relative to that of MIP-101 cells, consistent with the finding of
      decreased Fas on vesicles shed from the plasma membrane of CX-1 cells. Although
      mRNA for soluble Fas receptor is detectable in both cell lines, depletion of shed
      vesicles from serum-free medium by ultracentrifugation removes all detectable
      biological activity. FasL is detected on vesicles exfoliated from HuT 78 cells by
      immunoelectron microscopy and Western blot analysis. FasL-bearing vesicles induce
      apoptosis of Fas-expressing cancer cells at the same level as observed by
      treatment with monoclonal anti-Fas antibody. Furthermore, Fas-bearing
      extracellular vesicles from MIP-101 but not from CX-1 cells protect the CX-1 cell
      line from FasL-induced and anti-Fas-mediated apoptosis, indicating that Fas
      present on shed vesicles is biologically active. We conclude that the Fas antigen
      and its cognate ligand are exfoliated from the cell surface in a bioactive
      configuration. Exfoliation may provide a mechanism for long-range signal-directed
      apoptosis while maintaining Fas/FasL on a membrane surface.

PMID- 9573025
TI  - Functional diversity of the CD8(+) T-cell response to Epstein-Barr virus (EBV):
      implications for the pathogenesis of EBV-associated lymphoproliferative
      disorders.
AB  - Epstein-Barr virus (EBV)-specific CD8(+) cytotoxic T cells are thought to be
      critical for the control of EBV, which persists in healthy individuals as a
      latent infection of B cells. However, recent observations have indicated that
      CD8(+) T-cell responses are not uniformly cytotoxic and that CD8(+) T cells may
      be subdivided into type 1 and type 2 subsets that parallel the classically
      described Th1 and Th2 subsets of CD4(+) T cells. Using two-color flow cytometric
      analysis of intracellular cytokine expression at the single-cell level, we have
      identified two distinct but overlapping subsets of EBV-specific CD8(+) T cells,
      the first of which expressed high levels of interferon gamma (IFNgamma), but
      little or no interleukin-4 (IL-4), whereas the second subset was IFNgamma+/IL
      4(+) double-positive. A significant proportion of EBV-specific CD8(+) T cells
      also expressed IL-13. Subsequent analysis of a panel of 27 EBV-specific CD8(+) T
      cell clones showed inverse relationships between EBV-specific cytotoxicity and
      secretion of IL-4, IL-10, and IFNgamma, respectively. IL-10 was not secreted by
      the 11 most strongly cytotoxic clones, suggesting that IL-10 secretion may
      provide a functional definition of an EBV-specific type 2 CD8(+) T-cell subset
      with reduced EBV-specific cytotoxicity. Finally, we have demonstrated that EBV
      specific CD8(+) T cells that express type 2 cytokines possess the ability to
      activate resting B cells. EBV-specific CD8(+) T cells thus have the potential to
      reactivate latent EBV infection in vivo and may contribute to the development of
      EBV-associated lymphoproliferative disorders and lymphoma.

PMID- 9573026
TI  - Interleukin-13 receptor alpha' but not alpha chain: a functional component of
      interleukin-4 receptors.
AB  - In hematopoietic cells, interleukin-2 receptor (IL-2R) gamma chain (termed
      gammac) is shown to be a component of the IL-4R system, whereas in
      nonhematopoietic cells, gammac is absent and it is not a component of the IL-4R
      system. Here, we show that the IL-13R alpha' chain (termed IL-13Ralpha') but not
      the IL-13R alpha chain (termed IL-13Ralpha) can substitute for gammac and, thus,
      IL-13Ralpha' forms a novel component of the IL-4R system. This conclusion was
      drawn on the basis of chemical cross-linking, immunoprecipitation, the ability of
      IL-13Ralpha' but not IL-13Ralpha to augment IL-4 binding affinity, and the
      requirement of IL-13Ralpha' for IL-4-induced STAT6 activation in Chinese hamster
      ovary (CHO) cells transfected with various receptor subunits. Cotransfection of
      IL-4 receptor p140 (termed IL-4Rbeta) with gammac or IL-13Ralpha' increased IL-4
      binding affinity and allowed for STAT6 activation in response to IL-4. However,
      cotransfection of all three chains did not further increase IL-4 binding or alter
      the extent of STAT6 activation suggesting that all three chains together do not
      seem to participate in IL-4 function. Instead, IL-4Rbeta heterodimerizes with
      gammac or IL-13Ralpha' and mediates STAT6 activation. Cotransfection of IL-4Rbeta
      with IL-13Ralpha neither increased IL-4 binding affinity nor allowed for STAT6
      activation in response to IL-4 indicating that IL-13Ralpha does not convert
      binding affinity nor transmit signals for IL-4. Because IL-4 phosphorylates JAK1
      and JAK2 tyrosine kinases in nonhematopoietic cells, we investigated whether JAK1
      and JAK2 are required for IL-4-induced STAT6 activation in various transfectants.
      Cotransfection experiments with different chains of IL-4R and kinase-deficient
      JAK1 and JAK2 mutants in CHO cells showed that JAK1 and JAK2 are required for
      optimal activation of STAT6 in the alpha' beta transfectant but only partially in
      the beta gammac transfectant. Taken together, our results show that IL-13Ralpha'
      is a novel functional component of the IL-4R system and that JAK1 and JAK2
      mediate IL-4-induced optimal activation of STAT6 in nonhematopoietic cells.

PMID- 9573027
TI  - Expression of CD86 on human marrow CD34(+) cells identifies immunocompetent
      committed precursors of macrophages and dendritic cells.
AB  - Macrophages and dendritic cells derive from a hematopoietic stem cell and the
      existence of a common committed progenitor has been hypothesized. We have
      recently found in normal human marrow a subset of CD34(+) cells that
      constitutively expresses HLA-DR and low levels of CD86, a natural ligand for the
      T cell costimulation receptor CD28. This CD34(+) subset can elicit responses from
      allogeneic T cells. In this study, we show that CD34(+)/CD86(+) cells can also
      present tetanus toxoid antigen to memory CD4(+) T cells. CD86 is expressed at low
      levels in macrophages and high levels in dendritic cells. Therefore, we have
      tested the hypothesis that CD34(+)/CD86(+) cells are the common precursors of
      both macrophages and dendritic cells. CD34(+)/CD86(+) marrow cells cultured in
      granulocyte-macrophage colony-stimulating factor (GM-CSF)-generated macrophages.
      In contrast, CD34(+)/CD86(-) cells cultured in GM-CSF generated a predominant
      population of granulocytes. CD34(+)/CD86(+) cells cultured in GM-CSF plus tumor
      necrosis factor-alpha (TNF-alpha) generated almost exclusively CD1a+/CD83(+)
      dendritic cells. In contrast, CD34(+)/CD86(-) cells cultured in GM-CSF plus TNF
      alpha generated a variety of cell types, including a small population of
      dendritic cells. In addition, CD34(+)/CD86(+) cells cultured in granulocyte
      colony-stimulating factor failed to generate CD15(+) granulocytes. Therefore,
      CD34(+)/CD86(+) cells are committed precursors of both macrophages and dendritic
      cells. The ontogeny of dendritic cells was recapitulated by stimulation of
      CD34(+)/CD86(-) cells with TNF-alpha that induced expression of CD86. Subsequent
      costimulation of CD86(+) cells with GM-CSF plus TNF-alpha lead to expression of
      CD83 and produced terminal dendritic cell differentiation. Thus, expression of
      CD86 on hematopoietic progenitor cells is regulated by TNF-alpha and denotes
      differentiation towards the macrophage or dendritic cell lineages.

PMID- 9573028
TI  - CD44 selectively associates with active Src family protein tyrosine kinases Lck
      and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral
      blood lymphocytes.
AB  - CD44 is the major cell surface receptor for the extracellular matrix
      glycosaminoglycan hyaluronan and is implicated in a variety of biological events
      that include embryonic morphogenesis, lymphocyte recirculation, inflammation, and
      tumor metastasis. CD44 delivers activation signals to T lymphocytes, B
      lymphocytes, natural killer cells, polymorphonuclear leukocytes, and macrophages
      by stimulating protein tyrosine phosphorylation and calcium influx. The mechanism
      of signal transduction via CD44 remains undefined, although CD44 was shown to
      physically associate with intracellular protein tyrosine kinase Lck in T
      lymphocytes. In the present report, we show that a significant proportion of CD44
      in human peripheral blood T lymphocytes and endothelial cells is associated with
      low-density plasma membrane fractions that represent specialized plasma membrane
      domains enriched in glycosphingolipids and glycosylphosphatidylinositol (GPI)
      anchored proteins. CD44 and the GPI-anchored CD59 do not appear to directly
      interact in the low-density membrane fractions. In human peripheral blood T
      lymphocytes, 20% to 30% of the Src family protein tyrosine kinases, Lck and Fyn,
      are recovered from these fractions. CD44-associated protein kinase activity was
      selectively recovered from the low-density membrane fractions, corresponding to
      glycosphingolipid-rich plasma membrane microdomains. Reprecipitation of the in
      vitro phosphorylated proteins showed that CD44 associates not only with Lck but
      also with Fyn kinase in these membrane domains. Our results suggest that cellular
      stimulation via CD44 may proceed through the signaling machinery of
      glycosphingolipid-enriched plasma membrane microdomains and, hence, depend on the
      functional integrity of such domains.

PMID- 9573029
TI  - Constitutive chemokine production results in activation of leukocyte function
      associated antigen-1 on adult T-cell leukemia cells.
AB  - Adult T-cell leukemia (ATL) is characterized by massive infiltration of
      circulating ATL cells into a variety of tissues, a finding often associated with
      poor prognosis. Leukocyte migration from circulation into tissue depends on
      integrin-mediated adhesion to endothelium, and integrins are tightly regulated by
      several stimuli, such as inflammatory chemokines. However, the exact mechanisms
      that enhance adherence of leukemic cells to the endothelium and infiltration into
      tissues remain to be fully understood. We investigated the mechanisms of
      extravasation of leukemic cells using ATL cells and report the following novel
      features of endogenous chemokine-induced adhesion of ATL cells to the
      endothelium. ATL cells spontaneously adhered to endothelial cells without
      exogenous stimulation. Integrin leukocyte function-associated antigen-1 (LFA-1)
      on ATL cells was spontaneously activated. ATL cells produced high amounts of
      chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta.
      Adhesion of ATL cells to endothelial cells and the expression of activated form
      of LFA-1 were reduced by pretreatment with pertussis toxin, wortmannin, or anti
      MIP-1alpha and MIP-1beta antibodies or transfection with antisense of MIP-1alpha
      or MIP-1beta. Spontaneous polymerization of cytoskeletal F-actin was observed in
      ATL cells, which was also inhibited by pertussis toxin and wortmannin. We propose
      that ATL cells adhere to endothelial cells through an adhesion cascade similar to
      normal leukocytes and that the chemokines produced by ATL cells are involved in
      triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein
      dependent activation of phosphoinositide 3-kinases in an autocrine manner. These
      events result in a strong adhesion of ATL cells to the endothelium and
      spontaneous transendothelial migration.

PMID- 9573030
TI  - Inactivation of the ATM gene in T-cell prolymphocytic leukemias.
AB  - T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature leukemia that
      occurs both in adults as a sporadic disease and in younger patients suffering an
      hereditary condition, ataxia telangiectasia (AT). The ATM gene, located in the
      11q22-23 chromosomal region, is consistently mutated in AT patients. The strong
      predisposition of AT patients to develop T-PLL and the high frequency of T-cell
      leukemias/lymphomas observed in atm-deficient mice, together with the known
      functions of the ATM protein, led us to evaluate the ATM gene as a potential
      tumor suppressor gene involved in T-PLL. Paired leukemic and nonleukemic cells
      were obtained from a series of 15 patients suffering sporadic T-PLLs, allowing
      loss of heterozygosity (LOH) analysis. LOH of the 11q22-23 region was detected in
      10 of these 15 cases (67%). The minimal deleted region was defined as an
      approximately 2.5 Mb interval that contained the ATM gene. No ATM rearrangement
      or biallelic deletion was detected by Southern blotting in the T-PLL series.
      However, in five T-PLLs with LOH of the 11q22-23 region, Western blot analysis
      showed either undetectable (3 cases) or decreased levels (1 case) of ATM protein,
      whereas ATM was present at high levels in cases without LOH. The protein
      truncation test (PTT) was then used to search for mutations in the ATM gene. Four
      mutations (1 nonsense, 2 aberrant splicings, and 1 missense) were detected in
      patients with LOH and none in patients without LOH of the region. The acquired
      character of these ATM mutations was demonstrated in three patients. Altogether,
      allelic ATM inactivations by large deletions or mutations were found in
      approximately two thirds of T-PLL. ATM is thus a tumor suppressor gene whose
      inactivation is a key event in the development of T-cell prolymphocytic
      leukemias.

PMID- 9573031
TI  - Secondary mutation maintains the transformed state in BaF3 cells with inducible
      BCR/ABL expression.
AB  - The BCR/ABL gene product of the Philadelphia (Ph) chromosome induces chronic
      myelogenous leukemia (CML). We generated a hematopoietic cell line, TonB210.1,
      with tetracycline-dependent BCR/ABL expression to investigate the pathways by
      which BCR/ABL transforms cells. TonB210.1 demonstrates conditional growth factor
      independence in tissue culture and rapidly forms tumors in mice fed the
      tetracycline analog doxycycline. The tumors regress completely upon doxycycline
      withdrawal, but ultimately reform in all animals. After a long latency, tumors
      also develop in animals never exposed to doxycycline. Subclones of TonB210.1
      established from doxycycline-independent tumors demonstrate distinct mechanisms
      of transformation. Most subclones manifest increased basal levels of BCR/ABL
      expression; some have lost the capacity to augment expression upon induction,
      whereas others remain inducible. More interestingly, some subclones maintain
      tight conditional expression of BCR/ABL and are therefore transformed by
      secondary mechanisms that no longer require BCR/ABL expression. These subclones
      show constitutive phosphorylation of the STAT5 protein, suggesting that
      activating mutations have occurred upstream in the signaling pathway to STAT5.
      The tight conditional expression of BCR/ABL in the TonB210.1 cell line affords
      the opportunity to study several interesting aspects of the biology of BCR/ABL,
      including activation of critical signaling pathways and transcriptional programs,
      and its potential role in genomic instability.

PMID- 9573032
TI  - Mutation of CD95 (Fas/Apo-1) gene in adult T-cell leukemia cells.
AB  - CD95 antigen (also known as Fas or Apo-1) and Fas ligand play key roles in
      apoptosis of cells of the immune system, function as effector molecules of
      cytotoxic T lymphocytes, and function in the elimination of activated lymphocytes
      during the downregulation of the immune response. The critical roles of the Fas
      Fas ligand system in apoptosis suggest that its inactivation may be involved in
      malignant transformation. We analyzed the expression of Fas antigen on adult T
      cell leukemia (ATL) cells by flow cytometry and found that Fas antigen expression
      was absent in a case of ATL and markedly decreased in another case among 47 cases
      examined. Apoptosis could not be induced in the Fas-negative ATL cells by
      antibody against Fas antigen. Sequencing of reverse transcription-polymerase
      chain reaction products of the Fas genes in the Fas negative cells showed two
      types of aberrant transcripts: one had a 5-bp deletion and a 1-bp insertion in
      exon 2, and the other transcript lacked exon 4. These mutations caused the
      premature termination of both alleles, resulting in the loss of expression of
      surface Fas antigen. These aberrant transcripts were not detected in a
      nonleukemic B-cell line from the same patient. An RNase protection assay of the
      Fas gene showed mutations in 2 additional cases with Fas-positive ATL cells of 35
      cases examined: 1 case lacked exon 4 and the other was a silent mutation. In the
      Fas antigen-negative case, leukemic cells were resistant to anticancer drugs in
      vivo, indicating that the loss of expression of Fas antigen may be associated
      with a poor response to anticancer drugs. Indeed, Fas-negative ATL cells were
      resistant to adriamycin-induced apoptosis in vitro, which is consistent with the
      finding that ATL in this case was resistant to chemotherapy. These findings
      indicate that mutation of the Fas gene may be associated with the progression of
      ATL and with resistance to anticancer drugs.

PMID- 9573033
TI  - CD95 (APO-1/Fas) mutations in childhood T-lineage acute lymphoblastic leukemia.
AB  - CD95 (APO-1/Fas)-mediated apoptosis is pivotal in normal lymphocyte homeostasis
      and mutations of CD95 cause a benign autoimmune lymphoproliferation syndrome
      (ALPS) in humans and mice. However, tumors only rarely develop in these patients,
      and no CD95 mutations have yet been directly implicated in tumorigenesis. We
      therefore examined 81 de novo childhood T-lineage acute lymphoblastic leukemias
      (T-ALL) including 54 steroid-poor responders, 10 relapsed T-ALL, and 10 leukemic
      T-cell lines, for the presence of CD95 mutations using single-strand confirmation
      polymorphism and sequence analysis. In leukemic blasts and normal T cells of one
      patient, a heterozygous mutation in exon 3 of CD95 causing a 68Pro --> 68Leu
      change associated with decreased CD95-mediated apoptosis was found. In leukemic
      blasts and normal T cells of a second patient, a homozygous mutation in the
      promoter of CD95 causing disruption of a consensus sequence for AP-2 binding
      without decreasing constitutive CD95 expression was detected. No large intragenic
      alterations of CD95 were found, no homozygous loss was detected in the cell
      lines, and no CD95 mutations were detected in the relapses. The data presented
      here show that CD95 mutations occur in some T-ALL and may be of biological
      importance.

PMID- 9573034
TI  - The Ig heavy chain 3' end confers a posttranscriptional processing advantage to
      Bcl-2-IgH fusion RNA in t(14;18) lymphoma.
AB  - The chromosomal translocation t(14;18) in lymphoma leads to an overproduction of
      the Bcl-2 protein on the basis of increased Bcl-2 mRNA levels. Whereas the
      juxtaposition of Bcl-2 with the Ig heavy chain locus causes a transcriptional
      activation, 70% of the lymphomas also produce Bcl-2-Ig fusion RNAs with Ig 3'
      ends. Using S1 nuclease protection assays that can discriminate between nuclear
      RNA precursors and spliced mRNA, we found that the fusion RNAs in t(14;18) cell
      lines exhibit an additional posttranscriptional processing advantage.
      Transfection experiments with artificial genes containing various Bcl-2 or Ig 3'
      ends show that this effect is (1) related to RNA splicing and/or
      nucleocytoplasmic transport; (2) independent of transcriptional activation by the
      heavy chain enhancer; (3) dependent on the presence of the JH-CH and C-gamma1 Ig
      introns; and (4) tissue specific for B cells. This constitutes a novel mechanism
      of oncogene deregulation unrelated to transcriptional activation or half-life
      prolongation. The data further support the existence of a tissue-specific
      posttranscriptional pathway of Ig regulation in B cells.

PMID- 9573035
TI  - Clinical value of soluble IgG Fc receptor type III in plasma from patients with
      chronic idiopathic neutropenia.
AB  - Previous studies have shown that the plasma level of soluble IgG Fc receptor type
      III (sFcgammaRIII) is a measure of the total body neutrophil mass. The aim of
      this study was to determine whether the plasma level sFcgammaRIII is associated
      with the risk of contracting bacterial infections in patients with neutropenia.
      We collected blood from 66 patients suffering from acquired idiopathic
      neutropenia, whose blood was sent to our laboratory for diagnostic evaluation of
      neutropenia (neutrophil count <1,500 cells/microL). Soluble FcgammaRIII levels
      were measured in plasma. Genotype distibutions of FcgammaR polymorphisms were
      determined. Clinical data were obtained from the patient files. Patients were
      assessed as to whether or not they had suffered from a bacterial infection 3
      months before to 3 months after a single sFcgammaRIII measurement. In addition,
      longitudinal data were obtained from 21 patients. Of the 66 neutropenic patients
      who were included, 15 had suffered from a bacterial infection in the period 3
      months before to 3 months after sFcgammaRIII measurement. The age and sex
      distribution was equal among the groups with and without infections, as were the
      genotype frequencies of neutrophil FcgammaR polymorphisms. Both neutrophil count
      and plasma level sFcgammaRIII were significantly lower in the patient group with
      infections, compared with the noninfected group (P = .03 and P < .0001,
      respectively). No infections were reported for patients who had plasma
      sFcgammaRIII levels above 100 arbitrary units (AU; normal value, 30 to 200).
      After matching each infected patient with two noninfected patients having the
      same neutrophil count, sFcgammaRIII plasma levels remained significantly lower in
      the group with infections (P = . 0001). For the patients who were followed in
      time, no infections were reported when sFcgammaRIII levels were above 100 AU. In
      conclusion, our population of patients with chronic idiopathic neutropenia with
      plasma sFcgammaRIII levels above 100 AU did not show an increased risk of
      contracting bacterial infections.

PMID- 9573036
TI  - The related adhesion focal tyrosine kinase (RAFTK) is tyrosine phosphorylated and
      participates in colony-stimulating factor-1/macrophage colony-stimulating factor
      signaling in monocyte-macrophages.
AB  - RAFTK, a novel nonreceptor protein kinase, has been shown to be involved in focal
      adhesion signal transduction pathways in neuronal PC12 cells, megakaryocytes,
      platelets, and T cells. Because focal adhesions may modulate cytoskeletal
      functions and thereby alter phagocytosis, cell migration, and adhesion in
      monocyte-macrophages, we investigated the role of RAFTK signaling in these cells.
      RAFTK was abundantly expressed in THP1 monocytic cells as well as in primary
      alveolar and peripheral blood-derived macrophages. Colony-stimulating factor-1
      (CSF-1)/macrophage colony-stimulating factor (M-CSF) stimulation of THP1 cells
      increased the tyrosine phosphorylation of RAFTK; similar increases in
      phosphorylation were also detected after lipopolysaccharide stimulation. RAFTK
      was phosphorylated with similar kinetics in THP1 cells and peripheral blood
      derived macrophages. Immunoprecipitation analysis showed associations between
      RAFTK and the signaling molecule phosphatidylinositol-3 (PI-3) kinase. PI-3
      kinase enzyme activity also coprecipitated with the RAFTK antibody, further
      confirming this association. The CSF-1/M-CSF receptor c-fms and RAFTK appeared to
      associate in response to CSF-1/M-CSF treatment of THP1 cells. Inhibition of RAFTK
      by a dominant-negative kinase mutant reduced CSF-1/M-CSF-induced MAPK activity.
      These data indicate that RAFTK participates in signal transduction pathways
      mediated by CSF-1/M-CSF, a cytokine that regulates monocyte-macrophage growth and
      function.

PMID- 9573037
TI  - The effect of apotransferrin on iron release from Caco-2 cells, an intestinal
      epithelial cell line.
AB  - The Caco-2 cell line grown in bicameral chambers was used to study the effect of
      transferrin in the basal chamber on the transepithelial transport of iron. We
      have shown that when iron was offered as 59Fe on the apical surface of the Caco-2
      cells, transport of 59Fe into the basal chamber was stimulated by 50 micromol/L
      apotransferrin. Here, we examined the effect on 59Fe transport of lower
      concentrations of apotransferrin, as well as the effects on transport of ovo-,
      cobalt-, and ferri-transferrin and of iron chelators with an affinity for iron
      greater than that of transferrin. The stimulation of 59Fe transport was more
      sensitive to the presence of apotransferrin with a Km of 0.078 +/- 0.008
      micromol/L compared with ferri-transferrin with a Km of 1.24 +/- 0.39 micromol/L
      (P < .006). 59Fe transport was less sensitive to diethylenetriaminopenta-acetic
      acid (DTPA) than apotransferrin with Kms of 1.52 +/- 0.70. The chelator
      nitrilotriacetic acid (NTA) exhibited no stimulation of 59Fe transport. Analysis
      of laser scanning confocal micrographs showed that apotransferrin labeled with
      Texas Red is internalized by Caco-2 cells from the basal side and localizes in
      distinct vesicles above the nucleus. The sensitivity of apotransferrin in
      stimulating Fe transport suggests a unique interaction of apotransferrin with the
      basal surface of the intestinal epithelium.

PMID- 9573038
TI  - Examination of ferrochelatase mutations that cause erythropoietic protoporphyria.
AB  - Ferrochelatase (E.C. 4.99.1.1), the enzyme that catalyzes the terminal step in
      the heme biosynthetic pathway, is the site of defect in the human inherited
      disease erythropoietic protoporphyria (EPP). Previously it has been demonstrated
      that patients with EPP may have missense mutations leading to amino acid
      substitutions, early chain termination, or exon deletions. While it has been
      clearly demonstrated that two missense mutations result in lowered enzyme
      activity, it has never been shown what effect specific exon deletions may have.
      In the current work, recombinant human ferrochelatase has been engineered to have
      individual exon deletions corresponding to exons 3 through 11. When expressed in
      Escherichia coli, none of these possesses significant enzyme activity and all
      lack the [2Fe-2S] cluster. One of the human missense mutations, F417S, and a
      series of amino acid replacements at this site (ie, F417W, F417Y, and F417L) were
      examined. With the exception of F417L, all lacked enzyme activity and did not
      contain the [2Fe-2S] cluster in vivo or as isolated in vitro.

PMID- 9573039
TI  - Treatment of myeloproliferative disorders with hydroxyurea: effects on red blood
      cell geometry and deformability.
AB  - Hydroxyurea (HU) is used in suppressing the bone marrow and producing fetal-like
      red blood cells (RBCs). These RBCs are large in size and may theoretically
      disturb the microcirculation. In five patients with myeloproliferative disorders
      (MPD), the RBC geometry and deformability were analyzed before and after 6 to 8
      months of HU treatment. In untreated MPD, the RBC geometry and filterability was
      normal. After HU, the RBC membrane area increased 24% and the cell volume
      increased 39% (P <.005). This change resulted in a 12% increase in the minimum
      cylindrical diameter (MCD). From a static bending model of initial deformation,
      the RBC diametrical cross-section had a significantly increased section modulus.
      However, this increase in profile stiffness was compensated for by its larger
      projected cell area and, thus, pressure load on the RBC corpuscle. The resulting
      resistance to initial deformation therefore remained unchanged after HU. These
      findings were tested experimentally; with 3-microm filter membranes, HU treatment
      caused a significant increase in flow resistance (P <.02), in accordance with
      MCD. However, with 5-microm pores, no difference was seen, again in consonance
      with the theoretical findings of initial deformation. Because most capillaries
      are larger than 3 microm, we suggest that HU is acceptable from a perspective of
      cellular microrheology.

PMID- 9573040
TI  - Ironing out the kinks: splicing and translation in bacteria.

PMID- 9573041
TI  - RadA protein is an archaeal RecA protein homolog that catalyzes DNA strand
      exchange.
AB  - With the discovery that the Saccharomyces cerevisiae Rad51 protein is both
      structurally and functionally similar to the Escherichia coli RecA protein, the
      RecA paradigm for homologous recombination was extended to the Eucarya. The
      ubiquitous presence of RecA and Rad51 protein homologs raises the question of
      whether this archetypal protein exists within the third domain of life, the
      Archaea. Here we present the isolation of a Rad51/RecA protein homolog from the
      archaeon Sulfolobus solfataricus, and show that this protein, RadA, possesses the
      characteristics of a DNA strand exchange protein: The RadA protein is a DNA
      dependent ATPase, forms a nucleoprotein filament on DNA, and catalyzes DNA
      pairing and strand exchange.

PMID- 9573042
TI  - Characterization of a prokaryotic SMC protein involved in chromosome
      partitioning.
AB  - smc of Bacillus subtilis encodes a homolog of eukaryotic SMC proteins involved in
      chromosome condensation, pairing, and partitioning. A null mutation in B.
      subtilis smc caused a temperature-sensitive-lethal phenotype in rich medium.
      Under permissive conditions, the mutant had abnormal nucleoids, approximately 10%
      of the cells were anucleate, and assembly of foci of the chromosome partitioning
      protein Spo0J was altered. In combination with a null mutation in spo0J, the smc
      mutation caused a synthetic phenotype; cell growth was slower and approximately
      25% of the cells were anucleate. Our results demonstrate that the B. subtilis Smc
      protein, like its eukaryotic counterpart, plays an important role in chromosome
      structure and partitioning.

PMID- 9573043
TI  - osteoprotegerin-deficient mice develop early onset osteoporosis and arterial
      calcification.
AB  - Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation.
      In this study the physiological role of OPG is investigated by generating OPG
      deficient mice. Adolescent and adult OPG-/- mice exhibit a decrease in total bone
      density characterized by severe trabecular and cortical bone porosity, marked
      thinning of the parietal bones of the skull, and a high incidence of fractures.
      These findings demonstrate that OPG is a critical regulator of postnatal bone
      mass. Unexpectedly, OPG-deficient mice also exhibit medial calcification of the
      aorta and renal arteries, suggesting that regulation of OPG, its signaling
      pathway, or its ligand(s) may play a role in the long observed association
      between osteoporosis and vascular calcification.

PMID- 9573044
TI  - BXR, an embryonic orphan nuclear receptor activated by a novel class of
      endogenous benzoate metabolites.
AB  - Nuclear receptors are ligand-modulated transcription factors that respond to
      steroids, retinoids, and thyroid hormones to control development and body
      physiology. Orphan nuclear receptors, which lack identified ligands, provide a
      unique, and largely untapped, resource to discover new principles of physiologic
      homeostasis. We describe the isolation and characterization of the vertebrate
      orphan receptor, BXR, which heterodimerizes with RXR and binds high-affinity DNA
      sites composed of a variant thyroid hormone response element. A bioactivity
      guided screen of embryonic extracts revealed that BXR is activatable by low
      molecular-weight molecules with spectral patterns distinct from known nuclear
      receptor ligands. Mass spectrometry and 1H NMR analysis identified alkyl esters
      of amino and hydroxy benzoic acids as potent, stereoselective activators. In
      vitro cofactor association studies, along with competable binding of radiolabeled
      compounds, establish these molecules as bona fide ligands. Benzoates comprise a
      new molecular class of nuclear receptor ligand and their activity suggests that
      BXR may control a previously unsuspected vertebrate signaling pathway.

PMID- 9573045
TI  - The yeast Ada complex mediates the ligand-dependent activation function AF-2 of
      retinoid X and estrogen receptors.
AB  - Nuclear receptors can function as ligand-inducible transregulators in both
      mammalian and yeast cells, indicating that important features of control of
      transcription have been conserved throughout evolution. Here, we report the
      isolation and characterization of a yeast protein that exhibits properties
      expected for a coactivator/mediator of the ligand-dependent activation function
      AF-2 present in the ligand-binding domain (LBD, region E) of the retinoid X
      (RXRalpha) and estrogen (ERalpha) receptors. This protein is identical to Ada3, a
      component of the yeast Ada coactivator complex. We demonstrate that: (1) the
      region encompassing residues 347-702 of Ada3 interacts with the LBD of RXRalpha
      and ERalpha in a ligand-dependent manner in yeast; (2) this interaction
      corresponds to a direct binding and requires the integrity of the core of the AF
      2 activating domain (AF-2 AD) of both RXRalpha and ERalpha; (3) Ada3 as well as
      Ada2 and Gcn5, two other components of the Ada complex, are required for maximal
      AF-2 activity in yeast; and (4) Ada3 is able to enhance the AF-2 activity of
      RXRalpha and ERalpha when overexpressed in yeast and mammalian cells. Taken
      together, these data indicate that ligand-dependent transactivation by RXRalpha
      and ERalpha in yeast is mediated at least in part by the Ada complex, in which
      the Ada3 subunit directly binds to the holoreceptor LBD.

PMID- 9573046
TI  - Control of distal antennal identity and tarsal development in Drosophila by
      spineless-aristapedia, a homolog of the mammalian dioxin receptor.
AB  - We report the molecular characterization of the spineless (ss) gene of
      Drosophila, and present evidence that it plays a central role in defining the
      distal regions of both the antenna and leg. ss encodes the closest known homolog
      of the mammalian dioxin receptor, a transcription factor of the bHLH-PAS family.
      Loss-of-function alleles of ss cause three major phenotypes: transformation of
      distal antenna to leg, deletion of distal leg (tarsal) structures, and reduction
      in size of most bristles. Consistent with these phenotypes, ss is expressed in
      the distal portion of the antennal imaginal disc, the tarsal region of each leg
      disc, and in bristle precursor cells. Ectopic expression of ss causes
      transformation of the maxillary palp and distal leg to distal antenna, and
      induces formation of an ectopic antenna in the rostral membrane. These effects
      indicate that ss plays a primary role in specifying distal antennal identity. In
      the tarsus, ss is expressed only early, and is required for later expression of
      the tarsal gene bric a brac (bab). Ectopic expression causes the deletion of
      medial leg structures, suggesting that ss plays an instructive role in the
      establishment of the tarsal primordium. In both the antenna and leg, ss
      expression is shown to depend on Distal-less (Dll), a master regulator of ventral
      appendage formation. The antennal transformation and tarsal deletions caused by
      ss loss-of-function mutations are probably atavistic, suggesting that ss played a
      central role in the evolution of distal structures in arthropod limbs.

PMID- 9573048
TI  - Defective trophoblast function in mice with a targeted mutation of Ets2.
AB  - Members of the Ets family of transcription factors mediate transcriptional
      responses of multiple signaling pathways in diverse cell types and organisms.
      Targeted deletion of the conserved DNA binding domain of the Ets2 transcription
      factor results in the retardation and death of homozygous mouse embryos before
      8.5 days of embryonic development. Defects in extraembryonic tissue gene
      expression and function include deficient expression of matrix metalloproteinase
      9 (MMP-9, gelatinase B), persistent extracellular matrix, and failure of
      ectoplacental cone proliferation. Mutant embryos were rescued by aggregation with
      tetraploid mouse embryos, which complement the developmental defects by providing
      functional extraembryonic tissues. Rescued Ets2-deficient mice are viable and
      fertile but have wavy hair, curly whiskers, and abnormal hair follicle shape and
      arrangement, resembling mice with mutations of the EGF receptor or its ligands.
      However, these mice are not deficient in the production of TGFalpha or the EGF
      receptor. Homozygous mutant cell lines respond mitogenically to TGFalpha, EGF,
      FGF1, and FGF2. However, FGF fails to induce MMP-13 (collagenase-3) and MMP-3
      (stromelysin-1) in the Ets2-deficient fibroblasts. Ectopic expression of Ets2 in
      the deficient fibroblasts restores expression of both matrix metalloproteinases.
      Therefore, Ets2 is essential for placental function, mediating growth factor
      signaling to key target genes including MMP-3, MMP-9, and MMP-13 in different
      cell types, and for regulating hair development.

PMID- 9573047
TI  - Defects in regulation of apoptosis in caspase-2-deficient mice.
AB  - During embryonic development, a large number of cells die naturally to shape the
      new organism. Members of the caspase family of proteases are essential
      intracellular death effectors. Herein, we generated caspase-2-deficient mice to
      evaluate the requirement for this enzyme in various paradigms of apoptosis.
      Excess numbers of germ cells were endowed in ovaries of mutant mice and the
      oocytes were found to be resistant to cell death following exposure to
      chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was
      defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor
      neurons during development was accelerated in caspase-2-deficient mice. In
      addition, caspase-2-deficient sympathetic neurons underwent apoptosis more
      effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts
      both as a positive and negative cell death effector, depending upon cell lineage
      and stage of development.

PMID- 9573049
TI  - A ribosomal function is necessary for efficient splicing of the T4 phage
      thymidylate synthase intron in vivo.
AB  - Splicing of the group I intron of the T4 thymidylate synthase (td) gene was
      uncoupled from translation by introducing stop codons in the upstream exon. This
      resulted in severe splicing deficiency in vivo. Overexpression of a UGA
      suppressor tRNA partially rescued splicing, suggesting that this in vitro self
      splicing intron requires translation for splicing in vivo. Inhibition of
      translation by the antibiotics chloramphenicol and spectinomycin also resulted in
      splicing deficiency. Ribosomal protein S12, a protein with RNA chaperone
      activity, and CYT-18, a protein that stabilizes the three-dimensional structure
      of group I introns, efficiently rescued the stop codon mutants. We identified a
      region in the upstream exon that interferes with splicing. Point mutations in
      this region efficiently alleviate the effect of a nonsense codon. We infer from
      these results that the ribosome acts as an RNA chaperone to facilitate proper
      folding of the intron.

PMID- 9573050
TI  - The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide
      tails added by the SsrA-tagging system.
AB  - Interruption of translation in Escherichia coli can lead to the addition of an 11
      residue carboxy-terminal peptide tail to the nascent chain. This modification is
      mediated by SsrA RNA (also called 10Sa RNA and tmRNA) and marks the tagged
      polypeptide for proteolysis. Degradation in vivo of lambda repressor amino
      terminal domain variants bearing this carboxy-terminal SsrA peptide tag is shown
      here to depend on the cytoplasmic proteases ClpXP and ClpAP. Degradation in vitro
      of SsrA-tagged substrates was reproduced with purified components and required a
      substrate with a wild-type SsrA tail, the presence of both ClpP and either ClpA
      or ClpX, and ATP. Clp-dependent proteolysis accounts for most degradation of SsrA
      tagged amino-domain substrates at 32 degrees C, but additional proteases
      contribute to the degradation of some of these SsrA-tagged substrates at 39
      degrees C. The existence of multiple cytoplasmic proteases that function in SsrA
      quality-control surveillance suggests that the SsrA tag is designed to serve as a
      relatively promiscuous signal for proteolysis. Having diverse degradation systems
      able to recognize this tag may increase degradation capacity, permit degradation
      of a wide variety of different tagged proteins, or allow SsrA-tagged proteins to
      be degraded under different growth conditions.

PMID- 9573051
TI  - Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia
      coli protease HflB (FtsH).
AB  - Proteins with short nonpolar carboxyl termini are unstable in Escherichia coli.
      This proteolytic pathway is used to dispose of polypeptides synthesized from
      truncated mRNA molecules. Such proteins are tagged with an 11-amino-acid nonpolar
      destabilizing tail via a mechanism involving the 10Sa (SsrA) stable RNA and then
      degraded. We show here that the ATP-dependent zinc protease HflB (FtsH) is
      involved in the degradation of four unstable derivatives of the amino-terminal
      domain of the lambdacI repressor: three with nonpolar pentapeptide tails (cI104,
      cI105, cI108) and one with the SsrA tag (cI-SsrA). cI105 and cI-SsrA are also
      degraded by the ClpP-dependent proteases. Loss of ClpP can be compensated for by
      overproducing HflB. In an in vitro system, cI108 and cI-SsrA are degraded by HflB
      in an energy-dependent reaction, indicating that HflB itself recognizes the
      carboxyl terminus. These results establish a tail-specific pathway for removing
      abnormal cytoplasmic proteins via the HflB and Clp proteases.

PMID- 9573052
TI  - Pom1p, a fission yeast protein kinase that provides positional information for
      both polarized growth and cytokinesis.
AB  - Schizosaccharomyces pombe cells have a well-defined pattern of polarized growth
      at the cell ends during interphase and divide symmetrically into two equal-sized
      daughter cells. We identified a gene, pom1, that provides positional information
      for both growth and division in S. pombe. pom1 mutants form functioning growth
      zones and division septa but show several abnormalities: (1) After division,
      cells initiate growth with equal frequencies from either the old or the new end;
      (2) most cells never switch to bipolar growth but instead grow exclusively at the
      randomly chosen end; (3) some cells mislocalize their growth axis altogether,
      leading to the formation of angled and branched cells; and (4) many cells
      misplace and/or misorient their septa, leading to asymmetric cell division. pom1
      encodes a putative protein kinase that is concentrated at the new cell end during
      interphase, at both cell ends during mitosis, and at the septation site after
      mitosis. Small amounts of Pom1p are also found at the old cell end during
      interphase and associated with the actin ring during mitosis. Pom1p localization
      to the cell ends is independent of actin but requires microtubules and Tea1p.
      pom1 mutations are synthetically lethal with several other mutations that affect
      cytokinesis and/or the actin or microtubule cytoskeleton. Thus, Pom1p may
      position the growth and cytokinesis machineries by interaction with both the
      actin and microtubule cytoskeletons.

PMID- 9573053
TI  - Prespore-specific gene expression in Bacillus subtilis is driven by sequestration
      of SpoIIE phosphatase to the prespore side of the asymmetric septum.
AB  - The spoIIE gene is essential for the compartment-specific activation of
      transcription factor sigmaF during sporulation in Bacillus subtilis. SpoIIE is a
      membrane protein that is targeted to the potential sites of asymmetric septation
      near each pole of the sporulating cell. The cytoplasmic carboxy-terminal domain
      of SpoIIE contains a serine phosphatase that triggers the release of sigmaF in
      the prespore compartment after septation. To understand how septum-located SpoIIE
      is activated selectively in the prespore, we examined the distribution of a
      SpoIIE-GFP fusion protein. We show that the polar bands of SpoIIE protein
      actually form sequentially and that the most prominent band develops at the pole
      where the prespore forms. We also show that the protein is sequestered to the
      prespore side of the asymmetric septum. Sequestration of SpoIIE into the prespore
      compartment provides a mechanism that could explain the cell specificity of
      sigmaF activation.

PMID- 9573054
TI  - Suppression of crossing-over by DNA methylation in Ascobolus.
AB  - Homologous recombination between dispersed DNA repeats creates chromosomal
      rearrangements that are deleterious to the genome. The methylation associated
      with DNA repeats in many eukaryotes might serve to inhibit homologous
      recombination and play a role in preserving genome integrity. We have tested the
      hypothesis that DNA methylation suppresses meiotic recombination in the fungus
      Ascobolus immersus. The natural process of methylation-induced premeiotically
      (MIP) was used to methylate the b2 spore color gene, a 7.5-kb chromosomal
      recombination hot spot. The frequency of crossing-over between two markers
      flanking b2 was reduced several hundredfold when b2 was methylated on the two
      homologs. This demonstrates that DNA methylation strongly inhibits homologous
      recombination. When b2 was methylated on one homolog only, crossing-over was
      still reduced 50-fold, indicating that the effect of methylation cannot be
      limited to the blocking of initiation of recombination on the methylated homolog.
      On the basis of these and other observations, we propose that DNA methylation
      perturbs pairing between the two intact homologs before recombination initiation
      and/or impairs the normal processing of recombination intermediates.

PMID- 9573055
TI  - Molecular characterization of the Aeromonas hydrophila aroA gene and potential
      use of an auxotrophic aroA mutant as a live attenuated vaccine.
AB  - The aroA gene of Aeromonas hydrophila SO2/2, encoding 5-enolpyruvylshikimate 3
      phosphate synthase, was cloned by complementation of the aroA mutation in
      Escherichia coli K-12 strain AB2829, and the nucleotide sequence was determined.
      The nucleotide sequence of the A. hydrophila aroA gene encoded a protein of 440
      amino acids which showed a high degree of homology to other bacterial AroA
      proteins. To obtain an effective attenuated live vaccine against A. hydrophila
      infections in fish, the aroA gene was inactivated by the insertion of a DNA
      fragment containing a kanamycin resistance determinant and reintroduced by
      allelic exchange into the chromosome of A. hydrophila AG2 by means of the suicide
      vector pSUP202. The A. hydrophila mutant AG2 aroA::Ka(r) was highly attenuated
      when inoculated intraperitoneally into a rainbow trout, with a 50% lethal dose of
      >2 x 10(8) CFU. The mutants were not recoverable from the internal organs after
      48 h postinoculation. Immunohistochemical studies demonstrated that
      immunopositive materials, but not whole cells, reacting with a polyclonal
      antiserum against A. hydrophila were present in the kidney and spleen 9 days
      postinjection. Vaccination of rainbow trout with the AroA mutant as a live
      vaccine conferred significant protection against the wild-type strain of A.
      hydrophila.

PMID- 9573056
TI  - cagA-positive Helicobacter pylori populations in China and The Netherlands are
      distinct.
AB  - The aim of this research was to study whether and to what extent Chinese cagA
      positive Helicobacter pylori isolates differ from those in The Netherlands.
      Analysis of random amplified polymorphic DNA (RAPD)-PCR-assessed DNA fingerprints
      of chromosomal DNA of 24 cagA-positive H. pylori isolates from Dutch (n = 12) and
      Chinese (n = 10) patients yielded the absence of clustering. Based on comparison
      of the sequence of a 243-nucleotide part of cagA, the Dutch (group I) and Chinese
      (group II) H. pylori isolates formed two separate branches with high confidence
      limits in the phylogenetic tree. These two clusters were not observed when the
      sequence of a 240-bp part of glmM was used in the comparison. The number of
      nonsynonymous substitutions was much higher in cagA than in glmM, indicating
      positive selection. The average levels of divergence of cagA at the nucleotide
      and protein levels between group I and II isolates were found to be high, 13.3
      and 17.9%, respectively. Possibly, the pathogenicity island (PAI) that has been
      integrated into the chromosome of the ancestor of H. pylori now circulating in
      China contained a different cagA than the PAI that has been integrated into the
      chromosome of the ancestor of H. pylori now circulating in The Netherlands. We
      conclude that in China and The Netherlands, two distinct cagA-positive H. pylori
      populations are circulating.

PMID- 9573057
TI  - Proteasome-independent activation of nuclear factor kappaB in cytoplasmic
      extracts from human endothelial cells by Rickettsia rickettsii.
AB  - Interaction of many infectious agents with eukaryotic host cells is known to
      cause activation of the ubiquitous transcription factor nuclear factor kappaB (NF
      kappaB) (U. Siebenlist, G. Franzoso, and K. Brown, Annu. Rev. Cell Biol. 10:405
      455, 1994). Recently, we reported a biphasic pattern of NF-kappaB activation in
      cultured human umbilical vein endothelial cells consequent to infection with
      Rickettsia rickettsii, an obligate intracellular gram-negative bacterium and the
      etiologic agent of Rocky Mountain spotted fever (L. A. Sporn, S. K. Sahni, N. B.
      Lerner, V. J. Marder, D. J. Silverman, L. C. Turpin, and A. L. Schwab, Infect.
      Immun. 65:2786-2791, 1997). In the present study, we describe activation of NF
      kappaB in a cell-free system, accomplished by addition of partially purified R.
      rickettsii to endothelial cell cytoplasmic extracts. This activation was rapid,
      reaching maximal levels at 60 min, and was dependent on the number of R.
      rickettsii organisms added. Antibody supershift assays using monospecific
      antisera against NF-kappaB subunits (p50 and p65) confirmed the authenticity of
      the gel-shifted complexes and identified both p50-p50 homodimers and p50-p65
      heterodimers as constituents of the activated NF-kappaB pool. Activation occurred
      independently of the presence of endothelial cell membranes and was not inhibited
      by removal of the endothelial cell proteasome. Lack of involvement of the
      proteasome was further confirmed in assays using the peptide-aldehyde proteasome
      inhibitor MG 132. Activation was not ATP dependent since no change in activation
      resulted from addition of an excess of the unhydrolyzable ATP analog ATPgammaS,
      supplementation with exogenous ATP, or hydrolysis of endogenous ATP with ATPase.
      Furthermore, Western blot analysis before and after in vitro activation failed to
      demonstrate phosphorylation of serine 32 or degradation of the cytoplasmic pool
      of IkappaB alpha. This lack of IkappaB alpha involvement was supported by the
      finding that R. rickettsii can induce NF-kappaB activation in cytoplasmic
      extracts prepared from T24 bladder carcinoma cells and human embryo fibroblasts
      stably transfected with a superrepressor phosphorylation mutant of IkappaB alpha,
      rendering NF-kappaB inactivatable by many known signals. Thus, evidence is
      provided for a potentially novel NF-kappaB activation pathway wherein R.
      rickettsii may interact with and activate host cell transcriptional machinery
      independently of the involvement of the proteasome or known signal transduction
      pathways.

PMID- 9573058
TI  - Evidence that surface proteins Sn14 and Sn16 of Sarcocystis neurona merozoites
      are involved in infection and immunity.
AB  - Sarcocystis neurona is the etiologic agent of equine protozoal myeloencephalitis
      (EPM). Based on an analysis of 25,000 equine serum and cerebrospinal fluid (CSF)
      samples, including samples from horses with neurologic signs typical of EPM or
      with histologically or parasitologically confirmed EPM, four major immunoblot
      band patterns have been identified. Twenty-three serum and CSF samples
      representing each of the four immunoblot patterns were selected from 220 samples
      from horses with neurologic signs resembling EPM and examined for inhibitory
      effects on the infectivity of S. neurona by an in vitro neutralization assay. A
      high correlation between immunoblot band pattern and neutralizing activity was
      detected. Two proteins, Sn14 and Sn16 (14 and 16 kDa, respectively), appeared to
      be important for in vitro infection. A combination of the results of surface
      protein labeling, immunoprecipitation, Western blotting, and trypsin digestion
      suggests that these molecules are surface proteins and may be useful components
      of a vaccine against S. neurona infection. Although S. neurona is an obligate
      intracellular parasite, it is potentially a target for specific antibodies which
      may lyse merozoites via complement or inhibit their attachment and penetration to
      host cells.

PMID- 9573059
TI  - Helicobacter pylori glutamine synthetase lacks features associated with
      transcriptional and posttranslational regulation.
AB  - Helicobacter pylori urease, produced in abundance, is indispensable for the
      survival of H. pylori in animal hosts. Urea is hydrolyzed by the enzyme,
      resulting in the liberation of excess ammonia, some of which neutralizes gastric
      acid. The remaining ammonia is assimilated into protein by glutamine synthetase
      (EC 6.3.1.2), which catalyzes the reaction: NH3 + glutamate + ATP-->glutamine +
      ADP + Pi. We hypothesized that glutamine synthetase plays an unusually critical
      role in nitrogen assimilation by H. pylori. We developed a phenotypic screen to
      isolate genes that contribute to the synthesis of a catalytically active urease.
      Escherichia coli SE5000 transformed with plasmid pHP808 containing the entire H.
      pylori urease gene cluster was cotransformed with a pBluescript plasmid library
      of the H. pylori ATCC 43504 genome. A weakly urease-positive 9.4-kb clone,
      pUEF728, was subjected to nucleotide sequencing. Among other genes, the gene for
      glutamine synthetase was identified. The complete 1,443-bp glnA gene predicts a
      polypeptide of 481 amino acid residues with a molecular weight of 54,317; this
      was supported by maxicell analysis of cloned glnA expressed in E. coli. The top
      10 homologs were all bacterial glutamine synthetases, including Salmonella
      typhimurium glnA. The ATP-binding motif GDNGSG (residues 272 to 277) of H. pylori
      GlnA exactly matched and aligned with the sequence in 8 of the 10 homologs. The
      adenylation site found in the top 10 homologs (consensus sequence, NLYDLP) is
      replaced in H. pylori by NLFKLT (residues 405 to 410). Since the Tyr (Y) residue
      is the target of adenylation and since the H. pylori glutamine synthetase lacks
      that residue in four strains examined, we conclude that no adenylation occurs
      within this motif. Cloned H. pylori glnA complemented a glnA mutation in E. coli,
      and GlnA enzyme activity could be measured spectrophotometrically. In an attempt
      to produce a GlnA-deficient mutant of H. pylori, a kanamycin resistance cassette
      was cloned into the Tth111I site of H. pylori glnA. By using the standard
      technique of allelic exchange mutagenesis, no verifiable glutamine synthetase
      double-crossover mutant of strain UMAB41 could be isolated, suggesting that the
      mutation is lethal. We conclude that glutamine synthetase is critical for
      nitrogen assimilation in H. pylori and is active under all physiologic
      conditions.

PMID- 9573060
TI  - Cytokine induction in murine macrophages infected with virulent and avirulent
      Rhodococcus equi.
AB  - To look for a possible correlation between the virulence of Rhodococcus equi and
      its cytokine-inducing capacity, we evaluated intracellular survival and measured
      cytokine induction by mouse macrophages infected with a virulent strain
      containing an 85-kb plasmid and expressing VapA (103+), its avirulent plasmid
      cured derivative (103-), and heat-killed 103+ (HK). After incubation with similar
      numbers of bacteria, macrophages infected with 103- contained significantly more
      organisms than those infected with 103+ or HK. The number of bacteria in the
      macrophages infected with 103- and HK decreased progressively, whereas the 103+
      numbers remained constant over 48 h. Interleukin 1beta (IL-1beta), IL-6, IL-10,
      IL-12 p40, and tumor necrosis factor alpha (TNF-alpha) mRNA induction peaked at 4
      h and returned to baseline between 12 and 48 h postinfection. IL-1beta, IL-6, IL
      10, and TNF-alpha concentrations assessed by enzyme-linked immunosorbent assay
      generally agreed well with mRNA expression; IL-12 could, however, not be
      detected. For all the cytokines detected, mean concentrations in the supernatants
      were consistently higher in the 103(-)-infected monolayers than in those infected
      with 103+, although, with the exception of IL-1beta, the differences were not
      statistically significant. R. equi HK was a poor inducer of cytokine production.
      In conclusion, virulent and avirulent R. equi strains induced similar levels of
      cytokine synthesis. The slightly greater induction of most cytokines observed
      following infection with 103- is likely secondary to greater uptake by
      macrophages rather than to a direct role of VapA or another plasmid-encoded
      product in downregulating cytokine induction.

PMID- 9573061
TI  - Immunization of cattle by infection with Cowdria ruminantium elicits T
      lymphocytes that recognize autologous, infected endothelial cells and monocytes.
AB  - Peripheral blood mononuclear cells (PBMC) from immune cattle proliferate in the
      presence of autologous Cowdria ruminantium-infected endothelial cells and
      monocytes. Endothelial cells required treatment with T-cell growth factors to
      induce class II major histocompatibility complex expression prior to infection
      and use as stimulators. Proliferative responses to both infected autologous
      endothelial cells and monocytes were characterized by expansion of a mixture of
      CD4+, CD8+, and gammadelta T cells. However, gammadelta T cells dominated
      following several restimulations. Reverse transcription-PCR analysis of cytokine
      expression by C. ruminantium-specific T-cell lines and immune PBMC revealed weak
      interleukin-2 (IL-2), IL-4, and gamma interferon (IFN-gamma) transcripts at 3 to
      24 h after stimulation. Strong expression of IFN-gamma, tumor necrosis factor
      alpha (TNF-alpha), TNF-beta, and IL-2 receptor alpha-chain mRNA was detected in T
      cell lines 48 h after antigen stimulation. Supernatants from these T-cell
      cultures contained IFN-gamma protein. Our findings suggest that in immune cattle
      a C. ruminantium-specific T-cell response is induced and that infected
      endothelial cells and monocytes may present C. ruminantium antigens to specific T
      lymphocytes in vivo during infection and thereby play a role in induction of
      protective immune responses to the pathogen.

PMID- 9573062
TI  - Protective effects of a human 18-kilodalton cationic antimicrobial protein
      (CAP18)-derived peptide against murine endotoxemia.
AB  - CAP18 (an 18-kDa cationic antimicrobial protein) is a granulocyte-derived protein
      that can bind lipopolysaccharide (LPS) and inhibit various activities of LPS in
      vitro. The present study examined the protective effect of a synthetic 27-amino
      acid peptide (CAP18(109-135)) from the LPS-binding domain of CAP18 against
      antibiotic-induced endotoxin shock, using highly LPS-sensitive D-(+)
      galactosamine (D-GalN)-sensitized C3H/HeN mice. The antibiotic-induced endotoxin
      (CAZ-endotoxin) was prepared from the culture filtrate of Pseudomonas aeruginosa
      PAO1 exposed to ceftazidime (CAZ). Injection of CAP18(109-135) protected the mice
      injected with LPS or CAZ-endotoxin from death and lowered their tumor necrosis
      factor (TNF) levels in serum in a dose-dependent manner. Treatment with CAZ
      caused death of the D-GalN-sensitized P. aeruginosa PAO-infected mice within 48
      h, while injection with CAP18(109-135) rescued the mice from death. In the mice
      rescued from death by injection with CAP18(109-135), endotoxin levels in plasma
      and TNF production by liver tissues were decreased but the numbers of viable
      infecting bacteria in their blood were not decreased significantly and remained
      at the levels in CAZ-treated mice. These results indicate that CAP18(109-135) is
      capable of preventing antibiotic-induced endotoxic shock in mice with septicemia
      and that the effect is due to its LPS-neutralizing activity rather than to its
      antibacterial activity.

PMID- 9573063
TI  - Cytopathic effects of the major surface protein and the chymotrypsinlike protease
      of Treponema denticola.
AB  - Prominent antigens of Treponema denticola have been suggested to be mediators of
      the cytopathic effects typically seen in periodontal disease. In the present
      study of the T. denticola major surface protein (Msp) and the surface-expressed
      chymotrypsinlike protease complex (CTLP), we characterized the ability of these
      proteins to adhere to and lyse epithelial cells. Msp and CTLP were closely
      associated in spirochete outer membranes. Purified Msp, both native and
      recombinant, and CTLP bound to glutaraldehyde-fixed periodontal ligament
      epithelial cells. Adherence of Msp was partially blocked by specific antibodies.
      Adherence of CTLP was partially blocked by serine protease inhibitors and was
      further inhibited by specific antibodies. Both native Msp and CTLP were cytotoxic
      toward periodontal ligament epithelial cells, and their cytotoxicity was
      inhibited by the same treatments that inhibited adherence. Msp, but not CTLP,
      lysed erythrocytes. Msp complex (partially purified outer membranes free of
      protease activity) was cytotoxic toward a variety of different cell types. Pore
      forming activities of recombinant Msp in black lipid model membrane assays and in
      HeLa cell membranes were similar to those reported for the native protein,
      supporting the hypothesis that Msp cytotoxicity was due to its pore-forming
      activity.

PMID- 9573064
TI  - Role of YopP in suppression of tumor necrosis factor alpha release by macrophages
      during Yersinia infection.
AB  - The Yersinia plasmid-encoded Yop virulon enables extracellular adhering bacteria
      to deliver toxic effector proteins inside their target cells. It includes a type
      III secretion system (Ysc), at least two translocator proteins (YopB, YopD), and
      a set of intracellular Yop effectors (YopE, YopH, YopO, YopM, and YopP).
      Infection of macrophages with a wild-type strain leads to low levels of tumor
      necrosis factor alpha (TNF-alpha) release compared to infection with plasmid
      cured strains, suggesting that the virulence plasmid encodes a factor impairing
      the normal TNF-alpha response of infected macrophages. This effect is correlated
      with the inhibition of the macrophage mitogen-activated protein kinase (MAPK)
      activities. To identify the Yop protein responsible for the suppression of TNF
      alpha release, we infected J774A.1 and PU5-1.8 macrophages with a battery of
      knockout Yersinia enterocolitica mutants and we quantified the TNF-alpha
      released. Mutants affected in secretion (yscN), in translocation (yopB and yopD),
      or in synthesis of all the known Yop effectors (yopH, yopO, yopP, yopE, and yopM
      polymutants) were unable to block the TNF-alpha response of the macrophages. In
      contrast, single yopE, yopH, yopO, and yopM mutants behaved like the wild-type
      strain. A yopP mutant elicited elevated TNF-alpha release, and complementation of
      the yopP mutant or the yop effector polymutant strain with yopP alone led to a
      drop in TNF-alpha release. In addition, YopP was also responsible for the
      inhibition of the extracellular signal-regulated kinase2 (ERK2) and p38 MAPK
      activities. These results show that YopP is the Yop effector responsible for the
      Yersinia-induced suppression of TNF-alpha release by infected macrophages.

PMID- 9573065
TI  - Pasteurella haemolytica leukotoxin-induced increase in phospholipase A2 activity
      in bovine neutrophils.
AB  - Exposure of bovine neutrophils to Pasteurella haemolytica leukotoxin (LKT)
      stimulates the production of leukotriene B4 (LTB4), which is believed to be an
      important chemotactic agent in the development of acute fibrinopurulent pneumonic
      infection in cattle. The involvement of phospholipase A2 (PLA2) in LKT-induced
      synthesis of LTB4 was studied by using bovine neutrophils labeled with 3H
      arachidonate ([3H]AA). Incubation of isolated neutrophils with [3H]AA resulted in
      incorporation of radioactivity in the PLA2 substrates phosphatidylcholine,
      phosphatidylinositol, and phosphatidylethanolamine. Exposure of radiolabeled
      neutrophils to LKT caused concentration- and time-dependent release of
      radioactivity and redistribution of radioactivity in neutrophil membranes
      consistent with utilization of phosphoglyceride substrate and release of free
      fatty acid and eicosanoid products. These LKT-induced effects could be inhibited
      by pretreatment with arachidonyl trifluoromethyl ketone, an inhibitor of type IV
      cytoplasmic PLA2, and were dependent on extracellular calcium. These results
      support the conclusion that LKT-induced synthesis of LTB4 involves a calcium
      mediated increase in PLA2 activity.

PMID- 9573066
TI  - Synthesis and characterization of lipooligosaccharide-based conjugates as vaccine
      candidates for Moraxella (Branhamella) catarrhalis.
AB  - Moraxella (Branhamella) catarrhalis is an important cause of otitis media and
      sinusitis in children and of lower respiratory tract infections in adults.
      Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits
      bactericidal antibodies. Treatment of the LOS from strain ATCC 25238 with
      anhydrous hydrazine reduced its toxicity 20,000-fold, as assayed in the Limulus
      amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus
      toxoid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus
      influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS
      HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1,
      respectively. The antigenicity of the two conjugates was similar to that of the
      LOS, as determined by double immunodiffusion. Subcutaneous or intramuscular
      injection of both conjugates elicited a 50- to 100-fold rise in the geometric
      mean of immunoglobulin G (IgG) to the homologous LOS in mice after three
      injections and a 350- to 700-fold rise of anti-LOS IgG in rabbits after two
      injections. The immunogenicity of the conjugate was enhanced by formulation with
      monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced
      antisera had complement-mediated bactericidal activity against the homologous
      strain and heterologous strains of M. catarrhalis. These results indicate that a
      detoxified LOS-protein conjugate is a candidate for immunization against M.
      catarrhalis diseases.

PMID- 9573068
TI  - Hemoglobin-induced binding of Candida albicans to the cell-binding domain of
      fibronectin is independent of the Arg-Gly-Asp sequence.
AB  - Hemoglobin specifically induces fibronectin (FN) binding to the pathogenic yeast
      Candida albicans. When grown in the complex medium Sabouraud broth, C. albicans
      expresses receptors that bind to several domains of FN. Growth in defined medium
      supplemented with 0.1% hemoglobin, however, enhanced the binding of FN to a
      single class of receptors, with a Kd = 4.6 x 10(-8) M. Competitive binding assays
      using recombinant and proteolytic fragments of FN revealed that the cell-binding
      domain mediated this interaction. A recombinant 40-kDa fragment of FN consisting
      of type III repeats 9 to 13 had an inhibitory activity similar to that of the
      entire 120-kDa cell-binding domain, indicating that the C-terminal portion of the
      cell-binding domain contains the binding site. A recombinant 33-kDa fragment of
      the cell-binding domain and a 33-kDa fragment with the RGD sequence deleted had
      the same inhibitory activities, demonstrating that the RGD sequence recognized by
      some mammalian integrins is not required. The addition of hemoglobin to the
      culture medium also enhanced Candida cell adhesion to immobilized FN and to 120-
      and 40-kDa fragments of FN but not to the collagen-binding or fibrin I domains.
      Using ligand protection, we identified a surface protein from C. albicans with an
      apparent molecular mass of 55 kDa that was protected by both FN and the 40-kDa
      fragment derived from the cell-binding domain. Therefore, hemoglobin both induces
      FN binding and changes the relative affinities of C. albicans for the cell- and
      collagen-binding domains of FN.

PMID- 9573067
TI  - Identification of the aspartate-beta-semialdehyde dehydrogenase gene of
      Legionella pneumophila and characterization of a null mutant.
AB  - The ability of Legionella pneumophila to cause Legionnaires' disease is dependent
      on its capacity to survive in the intracellular environment of its host cells.
      Furthermore, outbreaks of this disease have been associated with contaminated
      water sources where L. pneumophila survives as a parasite of protozoa. In this
      study, we determined the effect of nutritional auxotrophy on the ability of L.
      pneumophila to survive in the intracellular environment of its host cells. We
      generated a diaminopimelic acid (DAP) auxotroph (AA400) of L. pneumophila by
      disruption of the aspartate-beta-semialdehyde (asd) gene. The ability of AA400 to
      survive within macrophages and protozoa was found to be defective. This defect
      was due solely to the asd disruption since complementation of the mutant with the
      wild-type asd gene restored its capacity for intracellular survival. Furthermore,
      the defect was not completely complemented by DAP supplementation to the culture
      media. Thus, our results suggest that disruption of the asd gene may prove to be
      useful in the design of attenuated vaccines against Legionnaires' disease.

PMID- 9573069
TI  - Genetic control of immune response to recombinant antigens carried by an
      attenuated Salmonella typhimurium vaccine strain: Nramp1 influences T-helper
      subset responses and protection against leishmanial challenge.
AB  - Attenuated strains of Salmonella typhimurium have been widely used as vehicles
      for delivery and expression of vaccine antigens in murine models of infectious
      disease. In mice, early bacterial replication following infection with S.
      typhimurium is controlled by the gene (Nramp1, formerly Ity/Lsh/Bcg) encoding the
      natural-resistance-associated macrophage protein (Nramp1). Nramp1 regulates
      macrophage activation and has multiple pleiotropic effects, including regulation
      of tumor necrosis factor alpha, interleukin 1beta (IL-1beta), and major
      histocompatibility complex class II molecules, all of which influence antigen
      processing and presentation. Nramp1 also has a direct effect on antigen
      processing, possibly by regulating the activity of proteases in the late
      endosomal compartment. Hence, there are multiple ways (regulation of bacterial
      load or recombinant antigen dose, class II molecule expression, costimulatory or
      adjuvant activity, and antigen processing) that Nramp1 might influence responses
      to recombinant salmonella vaccines. To test the hypothesis that Nramp1 influences
      responses to vaccination, congenic mouse strains have been used to analyze immune
      responses to recombinant antigens (tetanus toxoid antigen and leishmanial gp63)
      carried by live attenuated S. typhimurium aroA aroD mutants. Results show that
      congenic mice carrying the wild-type (S. typhimurium resistance) Nramp1 allele
      mount a predominantly T-helper-1 (IL-2 and gamma interferon) response to
      vaccination and show enhanced resolution of lesions following challenge infection
      with Leishmania major. In contrast, mice carrying mutant (S. typhimurium
      susceptibility) Nramp1 mount a T-helper-2 (immunoglobulin E and IL-4) response
      and show exacerbated lesion growth upon challenge.

PMID- 9573070
TI  - Comparisons between colony phase variation of Neisseria gonorrhoeae FA1090 and
      pilus, pilin, and S-pilin expression.
AB  - The gonococcal pilus is a primary virulence factor, providing the initial
      attachment of the bacterial cell to human mucosal tissues. Pilin, the major
      subunit of the pilus, can carry a wide spectrum of primary amino acid sequences
      which are generated by the action of a complex antigenic variation system.
      Changes in the pilin amino acid sequence can produce different pilus-dependent
      colony morphotypes, which have been previously shown to reflect phase variation
      of pili on the bacterial cell surface. In this study, we further examined the
      relationships between changes in pilus-dependent colony morphology, pilin
      sequence, pilus expression, and pilus function in Neisseria gonorrhoeae FA1090. A
      group of FA1090 colony variants expressed different pilin sequences and
      demonstrated different levels of pilin, S-pilin, and pilus expression. The
      analysis of these colony variants shows that they do not represent two distinct
      phases of pilus expression, but that changes in pilin protein sequence produce a
      spectrum of S-pilin production, pilus expression, and pilus aggregation levels.
      These different levels of pilus expression and aggregation influence not only
      colony morphology but also DNA transformation efficiency and epithelial cell
      adherence.

PMID- 9573071
TI  - Acquired resistance of Escherichia coli to complement lysis by binding of
      glycophosphoinositol-anchored protectin (CD59).
AB  - Protectin (CD59) is a glycophosphoinsitol (GPI)-anchored defender of human cells
      against lysis by the membrane attack complex of complement. In this study, we
      examined whether protectin released from human cell membranes can incorporate
      into the surface of gram-negative bacteria. Analysis by using radiolabeled
      protectin, immunofluorescence, flow cytometry, and whole-cell enzyme-linked
      immunosorbent assay demonstrated that protectin bound to nonencapsulated
      Escherichia coli EH237 (Re) and EH234 (Ra) in a calcium-dependent manner. The
      incorporation required the GPI-phospholipid moiety since no binding of a
      phospholipid-free soluble form of protectin was observed. Mg2+ did not enhance
      the binding, and a polysialic acid capsule prevented it (strain IH3080
      [O18:K1:H8]). Bound protectin inhibited the C5b-9 neoantigen expression on
      complement-treated bacteria. Protection against complement lysis was observed in
      both a colony counting assay and a bioluminescence assay, where viable EH234
      bacteria expressing the luciferase gene emitted green light in the presence of
      the luciferine substrate. In general, two- to four-times-higher serum
      concentrations were needed to obtain 50% lysis of protectin-coated versus
      noncoated bacteria. The results indicate that protectin can incorporate in a
      functionally active form into the cell membranes of the two nonencapsulated deep
      rough E. coli strains studied.

PMID- 9573072
TI  - Campylobacter jejuni cytolethal distending toxin causes a G2-phase cell cycle
      block.
AB  - Cytolethal distending toxin (CDT) from the diarrheagenic bacterium Campylobacter
      jejuni was shown to cause a rapid and specific cell cycle arrest in HeLa and Caco
      2 cells. Within 24 h of treatment, CDT caused HeLa cells to arrest with a 4N DNA
      content, indicative of cells in G2 or early M phase. Immunofluorescence studies
      indicated that the arrested cells had not entered M phase, since no evidence of
      tubulin reorganization or chromatin condensation was visible. CDT treatment was
      also shown to cause HeLa cells to accumulate the inactive, tyrosine
      phosphorylated form of CDC2. These results indicated that CDT treatment results
      in a failure to activate CDC2, which leads to cell cycle arrest in G2. This
      mechanism of action is novel for a bacterial toxin and provides a model for the
      generation of diarrheal disease by C. jejuni and other diarrheagenic bacteria
      that produce CDT.

PMID- 9573073
TI  - Participation of parasite surface glycoproteins in antibody-mediated protection
      of epithelial cells against Trichinella spiralis.
AB  - The L1 stage of the parasitic nematode Trichinella spiralis displays on its
      surface glycoproteins that are immunologically cross-reactive with several larval
      excretory-secretory (ES) products. The basis for the cross-reactivity is
      tyvelose, the terminal residue on the complex glycans shared by these surface and
      ES glycoproteins. In neonatal rats, tyvelose-specific monoclonal antibodies
      mediate the expulsion of larvae from the intestine. The aim of the studies
      described in this report was to determine how antibody binding to larval surfaces
      contributes to expulsion. In these experiments, which involve an in vitro assay
      of epithelial cell invasion, surface proteins on living larvae were biotinylated
      to distinguish them from ES products. Biotinylated and nonbiotinylated larvae
      were cocultured with avidin, biotin-specific antibodies, or anti-tyvelose
      monoclonal antibodies. Biotinylated larvae cultured with avidin or biotin
      specific antibodies invaded Madin-Darby canine kidney (MDCK) cells equally as
      well as biotinylated larvae cultured with medium alone. Anti-tyvelose monoclonal
      antibodies were highly protective in this assay; however, biotinylation of larval
      surfaces hindered the ability of anti-tyvelose monoclonal antibodies to prevent
      larval invasion of epithelial cells. This correlated with a reduction in the
      binding of anti-tyvelose antibody to biotinylated larval surfaces. Our results
      indicate that antibody binding to surface glycoproteins contributes to protection
      against T. spiralis invasion but that surface binding alone is not sufficient for
      protection. Our findings support the notion that protection is effected by cross
      linking of ES products to surface antigens.

PMID- 9573074
TI  - Integrins alpha(v)beta3 and alpha5beta1 mediate attachment of lyme disease
      spirochetes to human cells.
AB  - Borrelia burgdorferi (sensu lato), the agent of Lyme disease, is able to cause
      chronic, multisystemic infections in human and animal hosts. Attachment of the
      spirochete to host cells is likely to be important for the colonization of
      diverse tissues. The platelet-specific integrin alpha(IIb)beta3 was previously
      identified as a receptor for all three species of Lyme disease spirochetes (B.
      burgdorferi sensu stricto, B. garinii, and B. afzelii). Here we show that B.
      burgdorferi also recognizes the widely expressed integrins alpha(v)beta3 and
      alpha5beta1, known as the vitronectin and fibronectin receptors, respectively.
      Three representatives of each species of Lyme disease spirochete were tested for
      the ability to bind to purified alpha(v)beta3 and alpha5beta1. All of the strains
      tested bound to at least one integrin. Binding to one integrin was not always
      predictive of binding to other integrins, and several different integrin
      preference profiles were identified. Attachment of the infectious B. burgdorferi
      strain N40 to purified alpha(v)beta3 and alpha5beta1 was inhibited by RGD
      peptides and the appropriate receptor-specific antibodies. Binding to
      alpha(v)beta3 was also shown by using a transfected cell line that expresses this
      receptor but not alpha(IIb)beta3. Attachment of B. burgdorferi N40 to human
      erythroleukemia cells and to human saphenous vein endothelial cells was mediated
      by both alpha5beta1 and alpha(v)beta3. Our results show that multiple integrins
      mediate attachment of Lyme disease spirochetes to host cells.

PMID- 9573075
TI  - Cloning and sequencing of a Candida albicans catalase gene and effects of
      disruption of this gene.
AB  - Catalase plays a key role as an antioxidant, protecting aerobic organisms from
      the toxic effects of hydrogen peroxide, and in some cases has been postulated to
      be a virulence factor. To help elucidate the function of catalase in Candida
      albicans, a single C. albicans-derived catalase gene, designated CAT1, was
      isolated and cloned. Degenerate PCR primers based on highly conserved areas of
      other fungal catalase genes were used to amplify a 411-bp product from genomic
      DNA of C. albicans ATCC 10261. By using this product as a probe, catalase clones
      were isolated from genomic libraries of C. albicans. Nucleotide sequence analysis
      revealed an open reading frame encoding a protein of 487 amino acid residues.
      Construction of a CAT1-deficient mutant was achieved by using the Ura-blaster
      technique for sequential disruption of multiple alleles by integrative
      transformation using URA3 as a selectable marker. Resulting mutants exhibited
      normal morphology and comparable growth rates of both yeast and mycelial forms.
      Enzymatic analysis revealed an abundance of catalase in the wild-type strain but
      decreasing catalase activity in heterozygous mutants and no detectable catalase
      in a homozygous null mutant. In vitro assays showed the mutant strains to be more
      sensitive to damage by both neutrophils and concentrations of exogenous peroxide
      that were sublethal for the parental strain. Compared to the parental strain, the
      homozygous null mutant strain was far less virulent for mice in an intravenous
      infection model of disseminated candidiasis. Definitive linkage of CAT1 with
      virulence would require restoration of activity by reintroduction of the gene
      into mutants. However, initial results in mice, taken together with the enhanced
      susceptibility of catalase-deficient hyphae to damage by human neutrophils,
      suggest that catalase may enhance the pathogenicity of C. albicans.

PMID- 9573076
TI  - Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia
      in mice treated with liposome-encapsulated muramyl tripeptide
      phosphatidylethanolamine or gamma interferon.
AB  - We have previously shown that prophylactic administration of the liposome
      encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine
      (MTPPE) and gamma interferon (IFN-gamma) results in strongly increased survival
      of mice from a normally lethal septicemia with Klebsiella pneumoniae. It was
      anticipated that the treatment acts on macrophages and nonspecifically augments
      host resistance to various infections. In the present study, we provide evidence
      for a key role for T cells in host defense potentiation by the liposomal
      immunomodulators toward K. pneumoniae septicemia. It is shown that both CD4 and
      CD8 cells are important in immunomodulation, most likely due to production of IFN
      gamma. Depletion of circulating IFN-gamma resulted in strong reduction of the
      antimicrobial host defense activation. Administration of interleukin-10 resulted
      in decreased antimicrobial host defense activation by liposomal immunomodulators.
      Moreover, administration of liposomal immunomodulators was shown to induce
      predominantly T-helper type 1 (Th1) cell populations in the spleen. These
      findings indicate that immunomodulation with liposomal MTPPE and IFN-gamma favors
      Th1 and NK cell activation.

PMID- 9573077
TI  - Validation of a volunteer model of cholera with frozen bacteria as the challenge.
AB  - To evaluate a standardized inoculum of Vibrio cholerae for volunteer challenge
      studies, 40 healthy adult volunteers were challenged at three different
      institutions with a standard inoculum prepared directly from vials of frozen,
      virulent, El Tor Inaba V. cholerae N16961, with no further incubation. Groups of
      5 volunteers, with each group including 2 volunteers with blood group O, were
      given a dose of 10(5) CFU, and 34 of the 40 volunteers developed diarrhea (mean
      incubation time, 28 h). Transient fevers occurred in 15 (37.5%) of the
      volunteers. V. cholerae was excreted by 36 of 40 volunteers. Five additional
      volunteers received 10(4) CFU, and four developed diarrhea but with a lower
      average purging rate than required for the model. Of the 40 volunteers, 37
      developed rises in their vibriocidal and antitoxin titers similar to those in
      previous groups challenged with freshly harvested bacteria. We conclude that
      challenge with frozen bacteria results in a reproducible illness similar to that
      induced by freshly harvested bacteria. Use of this model should minimize
      differences in attack rates or severity when groups are challenged at different
      times and in different institutions.

PMID- 9573078
TI  - Nasopharyngeal colonization with nontypeable Haemophilus influenzae in
      chinchillas.
AB  - Colonization of the nasopharynx by a middle ear pathogen is the first step in the
      development of otitis media in humans. The establishment of an animal model of
      nasopharyngeal colonization would therefore be of great utility in assessing the
      potential protective ability of candidate vaccine antigens (especially adhesins)
      against otitis media. A chinchilla nasopharyngeal colonization model for
      nontypeable Haemophilus influenzae (NTHI) was developed with antibiotic-resistant
      strains. This model does not require coinfection with a virus. There was no
      significant difference in the efficiency of NTHI colonization between adult (1-
      to 2-year-old) and young (2- to 3-month-old) animals. However, the incidence of
      middle ear infection following nasopharyngeal colonization was significantly
      higher in young animals (83 to 89%) than in adult chinchillas (10 to 30%).
      Chinchillas that had recovered either from a previous middle ear infection caused
      by NTHI or from an infection by intranasal inoculation with NTHI were completely
      protected against nasopharyngeal colonization with a homologous strain and were
      found to be the best positive controls in protection studies. Systemic
      immunization of chinchillas with inactivated whole-cell preparations
      significantly protected animals not only against homologous NTHI colonization but
      also partially against heterologous NTHI infection. In all protected animals,
      significant serum anti-P6 and anti-HMW antibody responses were observed. The
      outer membrane P6 and high-molecular-weight (HMW) proteins appear to be promising
      candidate vaccine antigens to prevent nasopharyngeal colonization and middle ear
      infection caused by NTHI.

PMID- 9573079
TI  - Nonspecific binding of Clostridium difficile toxin A to murine immunoglobulins
      occurs via the fab component.
AB  - Clostridium difficile toxin A binds nonspecifically to a mouse monoclonal
      antibody (MAb) immunoglobulin G3 lambda chain [IgG3(lambda)], through the Fab
      component. This binding, which is retained even after boiling the MAb, is
      temperature dependent, with more toxin bound at 4 than 37 degrees C (P = 0.0024).
      The nonspecific binding was decreased by incubation of the IgG3 lambda MAb with
      alpha- or beta-galactosidase (P = 0.0001 and 0.029, respectively), indicating
      that toxin A binds to a carbohydrate moiety on the Fab. However, binding was not
      blocked by the Bandeiraea simplicifolia lectin BS-1, indicating that a terminal
      alpha-galactose may not be involved. Binding was also not affected by competitive
      assays with Lewis X antigen. The dependence on carbohydrate moieties in
      nonspecific binding was also shown for two other MAbs, IgA(kappa) and
      IgM(lambda), with demonstration of a significant reduction in binding with alpha
      galactosidase (P = 0.0001 and 0.0002, respectively) but not beta-galactosidase (P
      = 0.27 and 0.25, respectively).

PMID- 9573080
TI  - Adherence of human vaginal lactobacilli to vaginal epithelial cells and
      interaction with uropathogens.
AB  - Three strains of Lactobacillus, identified as Lactobacillus acidophilus,
      Lactobacillus gasseri, and Lactobacillus jensenii, were selected from among 70
      isolates from the vaginas of healthy premenopausal women for properties relevant
      to mucosal colonization or antagonism. All three self-aggregated and adhered to
      epithelial vaginal cells, displacing well-known vaginal pathogens, such as G.
      vaginalis, and inhibiting the growth in vitro of Escherichia coli and
      Streptococcus agalactiae. The surface components involved in self-aggregation
      appeared to be proteins for L. gasseri and lipoproteins for L. acidophilus and L.
      jensenii, as judged by susceptibility to treatment with appropriate degrading
      enzymes. The factors responsible for adherence to epithelial vaginal cells seemed
      to be glycoproteins (L. acidophilus and L. gasseri) and carbohydrate (L.
      jensenii). The receptors of the vaginal cells were glycolipids, which presumably
      were the targets of the competition observed between the lactobacilli and the
      pathogenic microbes.

PMID- 9573081
TI  - Defined deletion mutants demonstrate that the major secreted toxins are not
      essential for the virulence of Aeromonas salmonicida.
AB  - The importance of the two major extracellular enzymes of Aeromonas salmonicida,
      glycerophospholipid: cholesterol acyltransferase (GCAT) and a serine protease
      (AspA), to the pathology and mortality of salmonid fish with furunculosis had
      been indicated in toxicity studies. In this study, the genes encoding GCAT (satA)
      and AspA (aspA) have been cloned and mutagenized by marker replacement of
      internal deletions, and the constructs have been used for the creation of
      isogenic satA and aspA mutants of A. salmonicida. A pSUP202 derivative
      (pSUP202sac) carrying the sacRB genes was constructed to facilitate the selection
      of mutants. The requirement of serine protease for processing of pro-GCAT was
      demonstrated. Processing involved the removal of a short internal fragment.
      Surprisingly, pathogenicity trials revealed no major decrease in virulence of the
      A. salmonicida delta satA::kan or A. salmonicida delta aspA::kan mutants compared
      to the wild-type parent strains when Atlantic salmon (Salmo salar L.) were
      challenged by intraperitoneal injection. Moreover, using a cohabitation model,
      which more closely mimics the natural disease, there was also no significant
      decrease in the relative cumulative mortality following infection with either of
      the deletion mutants compared to the parent strain. Thus, although these two
      toxins may confer some competitive advantage to A. salmonicida, neither toxin is
      essential for the very high virulence of A. salmonicida in Atlantic salmon. This
      first report of defined deletion mutations within any proposed extracellular
      virulence factor of A. salmonicida raises crucial questions about the
      pathogenesis of this important fish pathogen.

PMID- 9573082
TI  - Identification of epitope and surface-exposed domains of Shigella flexneri
      invasion plasmid antigen D (IpaD).
AB  - Transport and surface expression of the invasion plasmid antigens (Ipa proteins)
      is an essential trait in the pathogenicity of Shigella spp. In addition to the
      type III protein secretion system encoded by the mxi/spa loci on the large
      virulence plasmid, transport of IpaB and IpaC into the surrounding medium is
      modulated by IpaD. To characterize the structural topography of IpaD, the Geysen
      epitope-mapping system was used to identify epitopes recognized by surface
      reactive monoclonal and polyclonal antibodies produced against purified
      recombinant IpaD or synthetic IpaD peptides. Surface-exposed epitopes of IpaD
      were confined to the first 180 amino acid residues, whereas epitopes in the
      carboxyl-terminal half were not exposed on the Shigella surface. By using
      convalescent-phase sera from 10 Shigella flexneri-infected monkeys, numerous
      epitopes were mapped within a surface-exposed region of IpaD between amino acid
      residues 14 and 77. Epitopes were also identified in the carboxyl-terminal half
      of IpaD with a few convalescent-phase sera. Comparison of IpaD epitope sequences
      with Salmonella SipD sequences indicated that very similar epitopes may exist in
      the carboxyl-terminal region of each protein whereas the IpaD epitopes in the
      surface-exposed amino-terminal region were unique for the Shigella protein.
      Although the IpaD and SipD homologs may play similar roles in transport, the
      dominant serum antibody response to IpaD is against the unique region of this
      protein exposed on the surface of the pathogen.

PMID- 9573083
TI  - Cell-contact-stimulated formation of filamentous appendages by Salmonella
      typhimurium does not depend on the type III secretion system encoded by
      Salmonella pathogenicity island 1.
AB  - The formation of filamentous appendages on Salmonella typhimurium has been
      implicated in the triggering of bacterial entry into host cells (C. C. Ginocchio,
      S. B. Olmsted, C. L. Wells, and J. E. Galan, Cell 76:717-724, 1994). We have
      examined the roles of cell contact and Salmonella pathogenicity island 1 (SPI1)
      in appendage formation by comparing the surface morphologies of a panel of S.
      typhimurium strains adherent to tissue culture inserts, to cultured epithelial
      cell lines, and to murine intestine. Scanning electron microscopy revealed short
      filamentous appendages 30 to 50 nm in diameter and up to 300 nm in length on many
      wild-type S. typhimurium bacteria adhering to both cultured epithelial cells and
      to murine Peyer's patch follicle-associated epithelia. Wild-type S. typhimurium
      adhering to cell-free culture inserts lacked these filamentous appendages but
      sometimes exhibited very short appendages which might represent a rudimentary
      form of the cell contact-stimulated filamentous appendages. Invasion-deficient S.
      typhimurium strains carrying mutations in components of SPI1 (invA, invG, sspC,
      and prgH) exhibited filamentous appendages similar to those on wild-type S.
      typhimurium when adhering to epithelial cells, demonstrating that formation of
      these appendages is not itself sufficient to trigger bacterial invasion. When
      adhering to cell-free culture inserts, an S. typhimurium invG mutant differed
      from its parent strain in that it lacked even the shorter surface appendages,
      suggesting that SPI1 may be involved in appendage formation in the absence of
      epithelia. Our data on S. typhimurium strains in the presence of cells provide
      compelling evidence that SPI1 is not an absolute requirement for the formation of
      the described filamentous appendages. However, appendage formation is controlled
      by PhoP/PhoQ since a PhoP-constitutive mutant very rarely possessed such
      appendages when adhering to any of the cell types examined.

PMID- 9573084
TI  - Antibodies to recombinant Clostridium difficile toxins A and B are an effective
      treatment and prevent relapse of C. difficile-associated disease in a hamster
      model of infection.
AB  - Clostridium difficile causes antibiotic-associated diarrhea and colitis in humans
      through the actions of toxin A and toxin B on the colonic mucosa. At present,
      broad-spectrum antibiotic drugs are used to treat this disease, and patients
      suffer from high relapse rates after termination of treatment. This study
      examined the role of both toxins in pathogenesis and the ability of orally
      administered avian antibodies against recombinant epitopes of toxin A and toxin B
      to treat C. difficile-associated disease (CDAD). DNA fragments representing the
      entire gene of each toxin were cloned, expressed, and affinity purified. Hens
      were immunized with these purified recombinant-protein fragments of toxin A and
      toxin B. Toxin-neutralizing antibodies fractionated from egg yolks were evaluated
      by a toxin neutralization assay in Syrian hamsters. The carboxy-terminal region
      of each toxin was most effective in generating toxin-neutralizing antibodies.
      With a hamster infection model, antibodies to both toxins A and B (CDAD
      antitoxin) were required to prevent morbidity and mortality from infection. In
      contrast to vancomycin, CDAD antitoxin prevented relapse and subsequent C.
      difficile reinfection in the hamsters. These results indicate that CDAD antitoxin
      may be effective in the treatment and management of CDAD in humans.

PMID- 9573085
TI  - Immunologic memory induced by a glycoconjugate vaccine in a murine adoptive
      lymphocyte transfer model.
AB  - We have developed an adoptive cell transfer model in mice to study the ability of
      a glycoprotein conjugate vaccine to induce immunologic memory for the
      polysaccharide moiety. We used type III capsular polysaccharide from the
      clinically relevant pathogen group B streptococci conjugated to tetanus toxoid
      (GBSIII-TT) as our model vaccine. GBS are a major cause of neonatal infections in
      humans, and type-specific antibodies to the capsular polysaccharide protect
      against invasive disease. Adoptive transfer of splenocytes from mice immunized
      with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic
      memory to naive recipient mice. The transfer of memory occurred in a dose
      dependent manner. The observed anamnestic immune response was characterized by
      (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to
      IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for
      the primary response in animals with cells transferred from placebo-immunized
      mice. The adoptive cell transfer model described in this paper can be used for at
      least two purposes: (i) to evaluate conjugate vaccines with different
      physicochemical properties for their ability to induce immunologic memory and
      (ii) to study the cellular interactions required for an immune response to these
      molecules.

PMID- 9573086
TI  - Burkholderia cepacia produces a hemolysin that is capable of inducing apoptosis
      and degranulation of mammalian phagocytes.
AB  - Burkholderia cepacia is an opportunistic pathogen that has become a major threat
      to individuals with cystic fibrosis (CF). In approximately 20% of patients,
      pulmonary colonization with B. cepacia leads to cepacia syndrome, a fatal
      fulminating pneumonia sometimes associated with septicemia. It has been reported
      that culture filtrates of clinically derived strains of B. cepacia are hemolytic.
      In this study, we have characterized a factor which contributes to this hemolytic
      activity and is secreted from B. cepacia J2315, a representative of the virulent
      and highly transmissible strain belonging to the recently described genomovar III
      grouping. Biochemical data from the described purification method for this
      hemolysin allows us to hypothesize that the toxin is a lipopeptide. As
      demonstrated for other lipopeptide toxins, the hemolysin from B. cepacia was
      surface active and lowered the surface tension of high-pressure liquid
      chromatography-grade water from 72.96 to 29.8 mN m(-1). Similar to reports for
      other pore-forming cytotoxins, low concentrations of the hemolysin were able to
      induce nucleosomal degradation consistent with apoptosis in human neutrophils and
      the mouse-derived macrophage-type cell line J774.2. Exposure of human neutrophils
      to higher concentrations of toxin resulted in increased activities of the
      neutrophil degranulation markers cathepsin G and elastase. Based on the results
      obtained in this study, we suggest a role that allows B. cepacia to thwart the
      immune response and a model of the events that may contribute to the severe
      inflammatory response in the lungs of CF patients.

PMID- 9573087
TI  - Characterization of the roles of hemolysin and other toxins in enteropathy caused
      by alpha-hemolytic Escherichia coli linked to human diarrhea.
AB  - Escherichia coli strains producing alpha-hemolysin have been associated with
      diarrhea in several studies, but it has not been clearly demonstrated that these
      strains are enteropathogens or that alpha-hemolysin is an enteric virulence
      factor. Such strains are generally regarded as avirulent commensals. We examined
      a collection of diarrhea-associated hemolytic E. coli (DHEC) strains for
      virulence factors. No strain produced classic enterotoxins, but they all produced
      an alpha-hemolysin that was indistinguishable from that of uropathogenic E. coli
      strains. DHEC strains also produced other toxins including cytotoxic necrotizing
      factor 1 (CNF1) and novel toxins, including a cell-detaching cytotoxin and a
      toxin that causes HeLa cell elongation. DHEC strains were enteropathogenic in the
      RITARD (reversible intestinal tie adult rabbit diarrhea) model of diarrhea,
      causing characteristic enteropathies, including inflammation, necrosis, and
      colonic cell hyperplasia in both small and large intestines. Alpha-hemolysin
      appeared to be a major virulence factor in this model since it conferred
      virulence to nonpathogenic E. coli strains. Other virulence factors also appear
      to be contributing to virulence. These findings support the epidemiologic link to
      diarrhea and suggest that further research into the role of DHEC and alpha
      hemolysin in enteric disease is warranted.

PMID- 9573089
TI  - Delivery of the p67 sporozoite antigen of Theileria parva by using recombinant
      Salmonella dublin: secretion of the product enhances specific antibody responses
      in cattle.
AB  - The p67 sporozoite antigen of Theileria parva has been fused to the C-terminal
      secretion signal of Escherichia coli hemolysin and expressed in secreted form by
      attenuated Salmonella dublin aroA strain SL5631. The recombinant p67 antigen was
      detected in the supernatant of transformed bacterial cultures. Immunization
      trials in cattle revealed that SL5631 secreting the antigen provoked a 10-fold
      higher antibody response to p67 than recombinant SL5631 expressing but not
      secreting p67. Immunized calves were challenged with a 80% lethal dose of T.
      parva sporozoites and monitored for the development of infection. Two of three
      calves immunized intramuscularly with the p67-secreting SL5631 strain were found
      to be protected, whereas only one of three animals immunized with the
      nonsecreting p67-expressing SL5631 strain was protected. This is the first
      demonstration that complete eukaryotic antigens fused to the C-terminal portion
      of E. coli hemolysin can be exported from attenuated Salmonella strains and that
      such exported antigens can protect cattle against subsequent parasite challenge.

PMID- 9573088
TI  - The cell wall-associated glyceraldehyde-3-phosphate dehydrogenase of Candida
      albicans is also a fibronectin and laminin binding protein.
AB  - By immunoelectron microscopy with a polyclonal antibody against the cytosolic
      glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Candida
      albicans (anti-GAPDH PAb), the protein was clearly detected at the outer surface
      of the cell wall, particularly on blastoconidia, as well as in the cytoplasm.
      Intact blastoconidia were able to adhere to fibronectin and laminin immobilized
      on microtiter plates, and this adhesion was markedly reduced by both the anti
      GAPDH PAb and soluble GAPDH from Saccharomyces cerevisiae. In addition,
      semiquantitative flow cytometry analysis with the anti-GAPDH PAb showed a
      decrease in antibody binding to cells in the presence of soluble fibronectin and
      laminin. Purified cytosolic C. albicans GAPDH was found to bind to fibronectin
      and laminin in a ligand Western blot assay. These observations suggest that the
      cell wall-associated form of the GAPDH in C. albicans could be involved in
      mediating adhesion of fungal cells to fibronectin and laminin, thus contributing
      to the attachment of the microorganism to host tissues and to the dissemination
      of Candida infection.

PMID- 9573090
TI  - Clearance of Borrelia burgdorferi may not be required for resistance to
      experimental lyme arthritis.
AB  - Infection of inbred mouse strains with Borrelia burgdorferi results in the
      development of experimental Lyme arthritis. The degree of arthritic pathology has
      been suggested to correlate with the level of spirochete burden within tissues.
      To investigate this further, we infected resistant DBA/2 (DBA) and susceptible
      C3H/HeJ (C3H) mice in the hind footpads and monitored arthritis development for
      21 days. To quantitate levels of spirochetes within tissues, we created a
      competitive PCR molecule containing modified ospA and fla gene segments. C3H mice
      developed severe arthritis of the tibiotarsal joints, while DBA mice developed
      only mild inflammation throughout the experimental period. At day 21, when the
      gross size and histologic composition of ankles revealed significant differences
      in arthritis between the strains, there was little difference in levels of
      spirochete DNA as determined by competitive PCR. Cultures of ankle tissue at day
      21 were also uniformly positive in both C3H and DBA animals and contained
      relatively similar levels of spirochetes. These results indicate that the
      presence of spirochetes in the ankles of experimental animals is not sufficient
      for arthritis development. Since arthritic and nonarthritic animals can harbor
      relatively equal spirochete burdens yet retain their distinct phenotypic
      outcomes, an aberrant or overly exuberant immune response may be an additional
      requirement for pathology in arthritis-prone mice.

PMID- 9573091
TI  - Binding of Porphyromonas gingivalis fimbriae to proline-rich glycoproteins in
      parotid saliva via a domain shared by major salivary components.
AB  - Porphyromonas gingivalis, a putative periodontopathogen, can bind to human saliva
      through its fimbriae. We previously found that salivary components from the
      submandibular and sublingual glands bind to P. gingivalis fimbriae and that
      acidic proline-rich protein (PRP) and statherin function as receptor molecules
      for fimbriae. In this study, we investigated the fimbria-binding components in
      parotid saliva. Fractionated human parotid saliva by gel-filtration
      chromatography was immobilized onto nitrocellulose membranes for the overlay
      assay following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      salivary components on the membrane were allowed to interact with fimbriae
      purified from P. gingivalis ATCC 33277, and the interacted fimbriae were probed
      with anti-fimbria antibodies. The fimbriae were shown to bind to two forms of
      proline-rich glycoproteins (PRGs) as well as to acidic PRPs and statherin.
      Moreover, fimbriae bound to several components of smaller molecular size which
      appeared to be acidic PRP variants and basic PRPs. Fimbriae bound strongly to the
      purified PRGs adsorbed onto hydroxyapatite (HAP) beads. In contrast, PRGs in
      solution failed to inhibit the fimbrial binding to the immobilized PRGs on the
      HAP beads. These findings suggest that the appearance of binding site(s) of PRGs
      can be ascribed to their conformational changes. We previously identified the
      distinct segments within PRP and statherin molecules that are involved in
      fimbrial binding. The peptides analogous to the binding regions of PRP and
      statherin (i.e., PRP-C and STN-C) markedly inhibit the binding of fimbriae to PRP
      and statherin immobilized on the HAP beads, respectively. The PRP-C significantly
      inhibited the binding of fimbriae to PRG-coated HAP beads as well as to PRP on
      HAP beads. The peptide did not affect the binding of fimbriae to statherin,
      whereas the STN-C showed no effect on the fimbrial binding to PRPs or PRGs. In
      the overlay assay, the PRP-C clearly diminished the interactions between the
      fimbriae and the various salivary components, including PRPs, the PRGs, and the
      components with smaller molecular sizes but not statherin. These results strongly
      suggest that fimbriae bind to salivary components (except statherin) via common
      peptide segments. It is also suggested that fimbriae bind to saliva through the
      two distinct binding domains of receptory salivary components: (i) PRGs and PRPs
      and (ii) statherin.

PMID- 9573092
TI  - Cloning and characterization of CAD1/AAF1, a gene from Candida albicans that
      induces adherence to endothelial cells after expression in Saccharomyces
      cerevisiae.
AB  - Adherence to the endothelial cell lining of the vasculature is probably a
      critical step in the egress of Candida albicans from the intravascular
      compartment. To identify potential adhesins that mediate the attachment of this
      organism to endothelial cells, a genomic library from C. albicans was used to
      transform a nonadherent strain of Saccharomyces cerevisiae. The population of
      transformed yeasts was enriched for highly adherent clones by repeated passages
      over endothelial cells. One clone which exhibited a fivefold increase in
      endothelial cell adherence, compared with S. cerevisiae transformed with vector
      alone, was identified. This organism also flocculated. The candidal DNA fragment
      within this adherent/flocculent organism was found to contain a single 1.8-kb
      open reading frame, which was designated CAD1. It was found to be identical to
      AAF1. The predicted protein encoded by CAD1/AAF1 contained features suggestive of
      a regulatory factor. Consistent with this finding, immunoelectron microscopy
      revealed that CAD1/AAF1 localized to the cytoplasm and nucleus but not the cell
      wall or plasma membrane of the transformed yeasts. Because yeasts transformed
      with CAD1/AAF1 both flocculated and exhibited increased endothelial cell
      adherence, the relationship between adherence and flocculation was examined. S.
      cerevisiae expressing either of two flocculation phenotypes, Flo1 or NewFlo,
      adhered to endothelial cells as avidly as did yeasts expressing CAD1/AAF1.
      Inhibition studies revealed that the flocculation phenotype induced by CAD1/AAF1
      was similar to Flo1. Thus, CAD1/AAF1 probably encodes a regulatory protein that
      stimulates endothelial cell adherence in S. cerevisiae by inducing a flocculation
      phenotype. Whether CAD1/AAF1 contributes to the adherence of C. albicans to
      endothelial cells remains to be determined.

PMID- 9573093
TI  - Identification of a homolog of CcpA catabolite repressor protein in Streptococcus
      mutans.
AB  - A locus containing a gene with homology to ccpA of other bacteria has been cloned
      from Streptococcus mutans LT11, sequenced, and named regM. Upstream of the regM
      gene, on the opposite strand, is a gene encoding an X-Pro dipeptidase, pepQ. A 14
      bp palindromic sequence with homology to the consensus catabolite-responsive
      element sequence lay in the promoter region between the two genes. To study the
      function of regM, the gene was inactivated by insertion of an antibiotic
      resistance marker. Diauxic growth of S. mutans on a number of sugars in the
      presence of glucose was not affected by disruption of regM. The loss of RegM
      increased glucose repression of alpha-galactosidase, mannitol-1-P dehydrogenase,
      and P-beta-galactosidase activities. These results suggest that while RegM can
      affect catabolite repression in S. mutans, it does not conform to the model
      proposed for CcpA in Bacillus subtilis.

PMID- 9573094
TI  - Reduced response to multiple vaccines sharing common protein epitopes that are
      administered simultaneously to infants.
AB  - The plethora of newly discovered vaccines implies that, in the future, many
      vaccines will have to be administered simultaneously to infants. We examined the
      potential interference with the immune response of several coadministered
      vaccines containing the same protein component, namely, tetanus toxoid (TT).
      Infants simultaneously receiving a tetravalent pneumococcal vaccine conjugated to
      TT (PncT) and a diphtheria-tetanus-pertussis-poliovirus-Haemophilus influenzae
      type b-tetanus conjugate vaccine showed significantly lower anti-H. influenzae
      type b polysaccharide (polyribosylribitol phosphate [PRP]) antibody
      concentrations than those receiving either a tetravalent pneumococcal vaccine
      conjugated to diphtheria toxoid or placebo. A dose range study showed that anti
      PRP antibody concentrations were inversely related to the TT content of the PncT
      vaccines administered in infancy. Postimmunization antitetanus antibody
      concentrations were also affected adversely as the TT content of the
      coadministered vaccines was increased. This phenomenon, which we believe derives
      from interference by a common protein carrier, should be taken into account when
      the introduction of an immunization program including multiple conjugate vaccines
      is considered.

PMID- 9573095
TI  - Identification of Salmonella typhimurium genes required for colonization of the
      chicken alimentary tract and for virulence in newly hatched chicks.
AB  - From a collection of 2,800 Tn5-TC1 transposon mutants of Salmonella typhimurium
      F98, 18 that showed reduced intestinal colonization of 3-week-old chicks were
      identified. The sites of transposon insertion were determined for most of the
      mutants and included insertions in the lipopolysaccharide biosynthesis genes
      rfaK, rfaY, rfbK, and rfbB and the genes dksA, clpB, hupA, and sipC. In addition,
      identification was made of an insertion into a novel gene that encodes a protein
      showing similarity to the IIC component of the mannose class of
      phosphoenolpyruvate-carbohydrate phosphotransferase systems, which we putatively
      called ptsC. Transduction of most of the transposon mutations to a fresh S.
      typhimurium F98 genetic background and construction of defined mutations in the
      rfbK, dksA, hupA, sipC, and ptsC genes of S. typhimurium F98 supported the role
      in colonization of all but the pts locus. The virulence of the rfbK, dksA, hupA,
      sipC, and ptsC defined mutants and clpB and rfaY transductants in 1-day-old
      chicks was tested. All but the ptsC and rfaY mutants were attenuated for
      virulence. A number of other phenotypes associated with some of the mutations are
      described.

PMID- 9573096
TI  - Expansion of Vgamma9 Vdelta2 T cells is triggered by Francisella tularensis
      derived phosphoantigens in tularemia but not after tularemia vaccination.
AB  - Tularemia is a disease caused by the facultative intracellular bacterium
      Francisella tularensis. Here we demonstrate that during the first weeks of
      infection, a significant increase in levels of Vgamma9 Vdelta2 cells occurred in
      peripheral blood: in 13 patients analyzed 7 to 18 days after the onset of
      disease, these lymphocytes represented, on average, 30.5% of CD3+ cells and
      nearly 100% of gammadelta+ T cells. By contrast, after vaccination with the live
      vaccine strain (LVS) of F. tularensis, only a minor increase occurred. Eleven
      days after vaccination, gammadelta T cells represented an average of 6.7% and
      Vgamma9 Vdelta2 cells represented an average of 5.3% of T cells, as in control
      subjects. Since derivatives of nonpeptidic pyrophosphorylated molecules, referred
      to as phosphoantigens, are powerful stimuli for Vgamma9 Vdelta2 cells, this
      observation prompted an investigation of phosphoantigens in F. tularensis
      strains. The F. tularensis phosphoantigens triggered in vitro a proliferative
      response of human Vgamma9 Vdelta2 peripheral blood leukocytes as well as a
      cytotoxic response and tumor necrosis factor release from a Vgamma9 Vdelta2 T
      cell clone. Quantitatively similar phosphoantigenic activity was detected in
      acellular extracts from two clinical isolates (FSC171 and Schu) and from LVS.
      Taken together, the chemical nature of the stimulus from the clinical isolates
      and the significant increase in levels of Vgamma9 Vdelta2 cells in peripheral
      blood of tularemia patients indicate that phosphoantigens produced by virulent
      strains of F. tularensis trigger in vivo expansion of gammadelta T cells in
      tularemia.

PMID- 9573097
TI  - Nitric oxide is produced by Cowdria ruminantium-infected bovine pulmonary
      endothelial cells in vitro and is stimulated by gamma interferon.
AB  - Nitric oxide (NO) is a labile inorganic free radical produced by NO synthase from
      the substrate L-arginine in various cells and tissues including endothelial
      cells. A substantial elevation of nitrite levels indicative of NO production
      occurred in cultures of Cowdria ruminantium-infected bovine pulmonary endothelial
      cells (BPEC) incubated in medium alone. Exposure of the infected cultures to
      recombinant bovine gamma interferon (BorIFN-gamma) resulted in more rapid
      production of NO, reduced viability of C. ruminantium, and induction of
      endothelial cell death. Significant inhibition of NO production was noted after
      addition of the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA),
      indicating that the increase in production occurred via the inducible NO synthase
      pathway. Reduction in the infectivity of C. ruminantium elementary bodies (EBs)
      occurred in a dose-dependent manner after incubation with the NO donor molecule S
      nitroso-N-acetyl-DL-penicillamine (SNAP) prior to infection of endothelial cells.
      The level of infection in cultures maintained in SNAP was reduced in a dose
      dependent manner with significant negative correlation between the final level of
      infection on day 7 and the level of SNAP (r = -0.96). It was established that
      pretreatment and cultivation of C. ruminantium EBs with the NO donor molecule
      SNAP reduced infectivity to cultures and viability of EBs with the implication
      that release of NO in vivo following infection of endothelial cells may have an
      effect upon the multiplication of the agent in the host animal and may be
      involved in the pathogenesis of heartwater through the effect of this molecule
      upon circulation.

PMID- 9573098
TI  - A tumor necrosis factor mimetic peptide activates a murine macrophage cell line
      to inhibit mycobacterial growth in a nitric oxide-dependent fashion.
AB  - The control of mycobacterial infections depends on the cytokine-mediated
      activation of mononuclear phagocytes to inhibit the growth of intracellular
      mycobacteria. Optimal activation requires the presence of T-cell-derived gamma
      interferon (IFN-gamma) and other signals, including tumor necrosis factor (TNF).
      Recently, an 11-mer peptide based on amino acids 70 to 80 of the human TNF
      sequence, TNF(70-80), was found to have TNF mimetic properties, which include the
      activation of human and mouse neutrophils to kill Plasmodia spp. Therefore, we
      investigated the capacity of TNF(70-80) to activate the murine macrophage cell
      line RAW264.7 infected with the vaccine strain Mycobacterium bovis bacillus
      Calmette-Guerin (BCG). When RAW264.7 cells were pretreated with human TNF or
      TNF(70-80) in the presence of IFN-gamma, there was a dose-dependent reduction in
      the replication of BCG as measured by the uptake of 3H-labeled uracil and a
      concomitant release of nitric oxide as measured by the nitrite in the culture
      supernatants. TNF- or TNF(70-80)-induced macrophage activation was dependent on
      IFN-gamma and was inhibited by neutralizing monoclonal antibody to human TNF and
      by anti-IFN-gamma antisera. Both nitrite release and BCG growth inhibition were
      abrogated by competitive inhibitors of L-arginine, which blocked the activation
      of inducible nitric oxide synthase. A soluble form of the Type 1 TNF receptor
      blocked the activation of BCG-infected macrophages by human TNF and TNF(70-80),
      demonstrating that the effect of TNF(70-80) is dependent on signaling through TNF
      receptor I. The mimetic effects of TNF(70-80) on macrophage activation in vitro
      suggest that treatment with TNF(70-80) may modulate mycobacterial infections in
      vivo.

PMID- 9573099
TI  - Kinetics of infection and effects on placental cell populations in a murine model
      of Chlamydia psittaci-induced abortion.
AB  - The anatomical progression of chlamydial infection was studied in different areas
      of the placenta, using a mouse model and two inoculation times: early pregnancy
      (day 7, group A) and midpregnancy (day 11, group B). The first population cells
      affected were decidual cells and neutrophils located just at the limits of the
      maternal and fetal placenta. The following invaded area was the layer of giant
      cells. Complete colonization of the maternal placenta occurred after day 15 of
      pregnancy independently of the inoculation time, the metrial gland being the last
      area to be invaded; numerous granulated metrial gland (GMG) cells were infected.
      Finally, chlamydial inclusions were observed in labyrinthine trophoblastic cells
      from day 18 of pregnancy onward. Since no fetal damage was observed, it seems
      that an indirect mechanism involving the lysis of GMG cells and neutrophil
      infiltration of the decidua and metrial gland may be the pathogenic mechanism
      that leads to abortion.

PMID- 9573100
TI  - Cloning of Syrian hamster (Mesocricetus auratus) cytokine cDNAs and analysis of
      cytokine mRNA expression in experimental visceral leishmaniasis.
AB  - The Syrian golden hamster (Mesocricetus auratus) is uniquely susceptible to a
      variety of intracellular pathogens and is an excellent model for a number of
      human infectious diseases. The molecular basis for this high level of
      susceptibility is unknown, and immunological studies related to this model have
      been limited by the lack of available reagents. In this report we describe the
      cloning and sequence analysis of portions of the Syrian hamster interleukin 2 (IL
      2), IL-4, gamma interferon (IFN-gamma), tumor necrosis factor alpha, IL-10, IL
      12p40, and transforming growth factor beta cDNAs. In addition, we examined the
      cytokine response to infection with the intracellular protozoan Leishmania
      donovani in this animal model. Sequence analysis of the hamster cytokines
      revealed 69 to 93% homology with the corresponding mouse, rat, and human
      nucleotide sequences and 48 to 100% homology with the deduced amino acid
      sequences. The hamster IFN-gamma, compared with the mouse and rat homologs, had
      an additional 17 amino acids at the C terminus that could decrease the biological
      activity of this molecule and thus contribute to the extreme susceptibility of
      this animal to intracellular pathogens. The splenic expression of these genes in
      response to infection with L. donovani, the cause of visceral leishmaniasis (VL),
      was determined by Northern blotting. VL in the hamster is a progressive, lethal
      disease which very closely mimics active human disease. In this model there was
      pronounced expression of the Th1 cytokine mRNAs, with transcripts being detected
      as early as 1 week postinfection. Basal expression of IL-4 in uninfected hamsters
      was prominent but did not increase in response to infection with L. donovani. IL
      12 transcript expression was detected at low levels in infected animals and
      paralleled the expression of IFN-gamma. Expression of IL-10, a potent macrophage
      deactivator, increased throughout the course of infection and could contribute to
      the progressive nature of this infection. These initial studies are the first to
      examine the molecular immunopathogenesis of a hamster model of VL infection and
      indicate that progressive disease in this model of VL is not associated with
      early polarization of the splenic cellular immune response toward a Th2 phenotype
      and away from a Th1 phenotype.

PMID- 9573101
TI  - Active and passive immunity against Borrelia burgdorferi decorin binding protein
      A (DbpA) protects against infection.
AB  - Borrelia burgdorferi, the spirochete that causes Lyme disease, binds decorin, a
      collagen-associated extracellular matrix proteoglycan found in the skin (the site
      of entry for the spirochete) and in many other tissues. Two borrelial adhesins
      that recognize this proteoglycan, decorin binding proteins A and B (DbpA and
      DbpB, respectively), have recently been identified. Infection of mice by low-dose
      B. burgdorferi challenge elicited antibodies against DbpA and DbpB that were
      sustained at high levels, suggesting that these antigens are expressed in vivo.
      Scanning immunoelectron microscopy showed that DbpA was surface accessible on
      intact borreliae. Passive administration of DbpA antiserum protected mice from
      infection following challenge with heterologous B. burgdorferi sensu stricto
      isolates, even when serum administration was delayed for up to 4 days after
      challenge. DbpA is the first antigen target identified that is capable of
      mediating immune resolution of early, localized B. burgdorferi infections. DbpA
      immunization also protected mice from B. burgdorferi challenge; DbpB immunization
      was much less effective. DbpA antiserum inhibited in vitro growth of many B.
      burgdorferi sensu lato isolates of diverse geographic, phylogenetic, and clinical
      origins. In combination, these findings support a role for DbpA in the
      immunoprophylaxis of Lyme disease and suggest that DbpA vaccines have the
      potential to eliminate early-stage B. burgdorferi infections.

PMID- 9573102
TI  - A 70-kilodalton recombinant heat shock protein of Candida albicans is highly
      immunogenic and enhances systemic murine candidiasis.
AB  - The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21
      kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter,
      respectively) were studied for their immunogenicity, including proinflammatory
      cytokine induction in vitro and in vivo, and protection in a murine model of
      hematogenous candidiasis. The whole protein and its two fragments were strong
      inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the
      prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70
      preparations were also recognized as CMI targets by peripheral blood mononuclear
      cells of healthy human subjects. Inoculation of CaHsp70 preparations into
      immunized mice induced rapid production of interleukin-6 (IL-6) and tumor
      necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and
      CaHsp70-Cter also induced gamma interferon (IFN-gamma), IL-12, and IL-10 but not
      IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from
      nonimmunized mice. In particular, the production of IFN-gamma was equal if not
      superior to that induced in the same cells by whole, heat-inactivated fungal
      cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4
      but not IL-12 was produced in addition to IFN-gamma upon in vitro stimulation of
      CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median
      survival time compared to nonimmunized mice, and their mortality was strictly
      associated with organ invasion by fungal hyphae. Their enhanced susceptibility
      was attributable to the immunization state, as it did not occur in congenitally
      athymic nude mice, which were unable to raise either Ab or CMI responses to
      CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity
      of CaHsp70, with which, however, no protection against but rather some
      enhancement of Candida infection seemed to occur in the mouse model used.

PMID- 9573103
TI  - Integrated physical and genetic mapping of Bacillus cereus and other gram
      positive bacteria based on IS231A transposition vectors.
AB  - The genome structure of Bacillus cereus is relatively complex, its DNA being
      modulated between a size-varying chromosome and large plasmids. To study the
      genetic organization of the B. cereus type strain ATCC 14579, thermosensitive
      transposition vectors were designed on the basis of IS231A-derived cassettes
      containing uncommon restriction sites. A highly preferred insertion site for
      IS231A was detected in the chromosome by Southern blotting and pulsed-field gel
      electrophoresis (PFGE) analyses of independent insertion mutants. However, once
      this insertional hot spot was occupied, secondary IS231A insertions occurred
      randomly, as demonstrated by isolation of independent B. cereus auxotrophs at a
      frequency of approximately 0.6%. The hot-spot site, as well as several
      auxotrophic mutations, were mapped by using NotI, SfiI, and AscI PFGE restriction
      profiles. It was confirmed by sequencing that one of the insertions, generating
      an Ade- phenotype, had disrupted a gene of the purine synthesis pathway. These
      results showed that combined PFGE and sequencing analyses of mini-IS231A
      insertions enable the construction of integrated physical and genetic maps of B.
      cereus type strain. Moreover, the presence of the ultrarare I-SceI restriction
      site in the mini-IS231A allowed the isolation, in double-insertion mutants, of
      contiguous and nonoverlapping large chromosomal fragments, convenient for direct
      sequencing. The system detailed in this report is therefore a powerful tool for
      comparative genetic studies among members of the B. cereus group (i.e., B.
      cereus, B. thuringiensis, B. mycoides, and B. anthracis) and could also be
      applied to more distantly related gram-positive bacteria.

PMID- 9573104
TI  - Generation of neutralizing antipeptide antibodies to the enzymatic domain of
      Pseudomonas aeruginosa exotoxin A.
AB  - Burn patients suffer a break in the physical barrier (skin), which, when combined
      with their generalized state of immunodeficiency, creates an open window for
      opportunistic infections, mainly with Pseudomonas aeruginosa. Infection of the
      burn wound has always been a major factor in retardation of wound healing, and
      sepsis remains the leading cause of death in burn patients. Because studies have
      shown that topical treatment with antiexotoxin A (ETA) antibodies significantly
      increases survival in rats infected with toxin-producing strains of P.
      aeruginosa, we examined 11 synthetic peptides encompassing 12 to 45 amino acid
      (aa) residues, representing what were predicted by computer analysis to be the
      most hydrophilic and antigenic regions of ETA. These synthetic peptides were
      injected into rabbits for antibody production. Different groups of rabbits were
      immunized with a combination of peptides, with each combination representing one
      of the three distinct domains of ETA. Animals immunized with various peptide
      combinations produced peptide-specific antibodies that exhibited cross-reactivity
      to ETA. Two major epitopes were identified on the ETA molecule by experiments
      with peptide-specific antibodies in enzyme-linked immunosorbent assay and
      immunoprecipitation. One of these epitopes was located in the translocation
      domain (II) (aa 297 to 310), while the other was mapped to the last 13 aa
      residues at the carboxy-terminal end of the enzymatic domain (III) (aa 626 to
      638). Of these two regions, the epitope in the enzymatic domain induced a much
      higher level of neutralizing antibodies that abrogated the cytotoxic activity of
      ETA in vitro. Antibodies to this epitope blocked the ADP-ribosyltransferase
      activity of ETA and appeared to interfere with binding of the substrate
      elongation factor 2 to the enzymatic active site of the ETA molecule. We conclude
      that polyclonal, as well as monoclonal, antibodies to short peptides,
      representing small regions of ETA, may have therapeutic potential in passive
      immunization or topical treatment of burn patients infected with toxin-producing
      strains of P. aeruginosa.

PMID- 9573105
TI  - Inactivation of the gbpA gene of Streptococcus mutans increases virulence and
      promotes in vivo accumulation of recombinations between the glucosyltransferase B
      and C genes.
AB  - Glucan-binding protein A (GbpA) of Streptococcus mutans has been hypothesized to
      promote sucrose-dependent adherence and the cohesiveness of plaque and therefore
      to contribute to caries formation. We have analyzed the adherence properties and
      virulence of isogenic gbpA mutants relative to those of wild-type S. mutans.
      Contrary to expectations, the gbpA mutant strains displayed enhanced sucrose
      dependent adherence in vitro and enhanced cariogenicity in vivo. In vitro, S.
      mutans was grown in the presence of [3H] thymidine and sucrose within glass
      vials. When grown with constant rotation, significantly higher levels of gbpA
      mutant organisms than of wild type remained adherent to the vial walls.
      Postgrowth vortexing of rotated cultures significantly decreased adherence of
      wild-type organisms, whereas the adherence of gbpA mutant organisms was
      unaffected. In the gnotobiotic rat model, the gbpA mutant strain was
      hypercariogenic though the colonization levels were not significantly different
      from those of the wild type. The gbpA mutant strain became enriched in vivo with
      organisms that had undergone a recombination involving the gtfB and gtfC genes.
      The incidence of gtfBC recombinant organisms increased as a function of dietary
      sucrose availability and was inversely correlated with caries development. We
      propose that the absence of GbpA elevates the cariogenic potential of S. mutans
      by altering the structure of plaque. However, the hypercariogenic plaque
      generated by gbpA mutant organisms may be suboptimal for S. mutans, leading to
      the accumulation of gtfBC recombinants whose reduced glucosyltransferase activity
      restores a less cariogenic plaque structure.

PMID- 9573106
TI  - Structural properties of group B streptococcal type III polysaccharide conjugate
      vaccines that influence immunogenicity and efficacy.
AB  - In this study, we tested the hypothesis that the immunogenicity and protective
      efficacy of polysaccharide-protein conjugate vaccines are influenced by three
      variables: (i) molecular size of the conjugate, (ii) molecular size of the
      polysaccharide used for conjugation, and (iii) extent of polysaccharide-to
      protein cross-linking. Type III group B Streptococcus capsular polysaccharide was
      linked by reductive amination at multiple sites to tetanus toxoid to create a
      polysaccharide-protein conjugate (III-TT). A single lot of III-TT was
      fractionated into small, medium, and large Mr pools. Whereas all three conferred
      protection in a maternal immunization-neonatal challenge model in mice, the
      smallest Mr conjugate evoked less polysaccharide-specific immunoglobulin G (IgG)
      than the two larger Mr conjugates. To test whether the molecular size of the
      polysaccharide used for conjugation also affected the immunogenicity of the
      conjugate, vaccines were synthesized using capsular polysaccharides with Mrs of
      38,000, 105,000, and 349,000. Polysaccharide-specific IgG responses in mice
      increased with the Mr of the polysaccharides, and protective efficacy was lower
      for the smallest polysaccharide conjugate compared to the other two vaccines.
      Immunogenicity testing of a series of vaccines prepared with different degrees of
      polysaccharide-to-protein cross-linking demonstrated higher polysaccharide
      specific antibody responses as the extent of cross-linking increased. However,
      opsonic activity was greatest in mouse antiserum raised to a moderately cross
      linked conjugate, suggesting that some antibodies evoked by highly cross-linked
      conjugates were directed to a nonprotective epitope. We conclude that conjugate
      size, polysaccharide size, and degree of polysaccharide-protein cross-linking
      influence the immunogenicity and protective efficacy of III-TT conjugate
      vaccines.

PMID- 9573107
TI  - Changes in murine jejunal morphology evoked by the bacterial superantigen
      Staphylococcus aureus enterotoxin B are mediated by CD4+ T cells.
AB  - Bacterial superantigens (SAgs) are potent T-cell stimuli that have been
      implicated in the pathophysiology of autoimmune and inflammatory disease. We used
      Staphylococcus aureus enterotoxin B (SEB) as a model SAg to assess the effects of
      SAg exposure on gut form and cellularity. BALB/c, SCID (lacking T cells) and T
      cell-reconstituted SCID mice were treated with SEB (5 or 100 microg
      intraperitoneally), and segments of the mid-jejunum were removed 4, 12, or 48 h
      later and processed for histochemical or immunocytochemical analysis of gut
      morphology and major histocompatibility complex class II (MHC II) expression and
      the enumeration of CD3+ T cells and goblet cells. Control mice received saline
      only. SEB treatment of BALB/c mice caused a time- and dose-dependent enteropathy
      that was characterized by reduced villus height, increased crypt depth, and a
      significant increase in MHC II expression. An increase in the number of CD3+ T
      cells was observed 48 h after exposure to 100 microg of SEB. Enteric structural
      alterations were not apparent in SEB-treated SCID mice compared to saline-treated
      SCID mice. In contrast, SEB challenge of SCID mice reconstituted with a mixed
      lymphocyte population or purified murine CD4+ T cells resulted in enteric
      histopathological changes reminiscent of those observed in SEB-treated BALB/c
      mice. These findings implicate CD4+ T cells in this SEB-induced enteropathy. Our
      results show that SAg immune activation causes significant changes in jejunal
      villus-crypt architecture and cellularity that are likely to impact on normal
      physiological processes. We speculate that the elevated MHC II expression and
      increased number of T cells could allow for enhanced immune responsiveness to
      other SAgs or environmental antigens.

PMID- 9573108
TI  - Production of proinflammatory cytokines and inflammatory mediators in human
      intestinal epithelial cells after invasion by Trichinella spiralis.
AB  - Epithelial cells are the first point of host contact for invasive intestinal
      pathogens and may initiate mucosal inflammatory responses via production of
      proinflammatory cytokines and mediators. The aim of the present study was to
      investigate in vitro the initial invasion of a parasitic nematode (Trichinella
      spiralis), to measure the early production of specific epithelial cytokines and
      inflammatory mediators after invasion, and to compare these responses with those
      to invasive bacteria. Monolayers of human colonic epithelial cell lines (HT29,
      T84, and Caco-2) were infected by T. spiralis or Listeria monocytogenes. Bile
      activated infective larvae of T. spiralis invaded and migrated into the
      epithelial cell monolayers, leaving trails of dead cells. Transmission electron
      microscopy studies of damaged cells along the trail showed a progressive increase
      in size, disruption of cell membranes, loss or dilution of cytoplasmic proteins,
      and swelling of mitochondria and nuclei. However, no nuclear fragmentation was
      observed. With reverse transcription-PCR and an enzyme-linked oligonucleotide
      chemiluminescent assay, mRNA transcripts of interleukin-1beta (IL-1beta), IL-8,
      and epithelial neutrophil-activating peptide 78 were shown to increase in
      epithelial cells invaded by T. spiralis or L. monocytogenes, but only L.
      monocytogenes elicited increased inducible nitric oxide synthase (iNOS) mRNA. No
      increase in tumor necrosis factor alpha or transforming growth factor beta mRNA
      was seen after T. spiralis invasion. Increased levels of IL-8 were also released
      from the basolateral surfaces of infected monolayers as detected by sandwich
      enzyme-linked immunosorbent assay. Induction and secretion of proinflammatory
      cytokines in epithelial cells after nematode or bacterial invasion may initiate
      the acute inflammatory response of the small intestine. The upregulation of iNOS
      in bacterial infections may contribute to mucosal defense and may also be
      associated with subsequent cell death, whereas different mechanisms appear to
      operate after nematode invasion.

PMID- 9573109
TI  - Construction of a functional single-chain variable fragment antibody against
      hemagglutinin from Porphyromonas gingivalis.
AB  - Hemagglutinin is a major glycoprotein of Porphyromonas gingivalis vesicles and
      likely confers the ability to adsorb and penetrate into host tissue cells. To
      protect this bacterial invasion, murine monoclonal antibody (MAb) Pg-vc, which
      inhibited the hemagglutinating activity, was prepared by using P. gingivalis
      vesicles as an antigen. Western blot analysis revealed that when both MAb Pg-vc
      and anti-HA-Ag2 antibody raised against the P. gingivalis hemagglutinin adhesin
      (M. Deslauriers and C. Mouton, Infect. Immun. 60:2791-2799, 1992) were allowed to
      react with protein blots from P. gingivalis vesicles, a superimposable profile
      was observed. To obtain a recombinant antibody, cDNAs coding for the variable
      domains of the L and H chains of MAb Pg-vc were cloned by PCR, and a plasmid
      specifying a single-chain variable fragment (ScFv) was constructed. Following
      transformation of Escherichia coli cells, a recombinant ScFv protein was
      successfully expressed. The immunological properties of this protein were
      identical to those of the parental murine MAb, specifically recognizing the two
      proteins (43 and 49 kDa) originating from P. gingivalis vesicles. In addition,
      the ScFv antibody inhibited the P. gingivalis vesicle-associated hemagglutinating
      activity. The amino acid sequences deduced from nucleotide sequencing experiments
      confirmed that variable heavy-chain and variable light-chain regions belonged to
      VH1 and Vkappa12/13 families, respectively. Since the expression system used in
      this study can readily provide large quantities of single-chain recombinant
      antibody, it may be a useful in developing a therapeutic agent for passive
      immunization in humans.

PMID- 9573110
TI  - Ambiguous role of interleukin-12 in Yersinia enterocolitica infection in
      susceptible and resistant mouse strains.
AB  - Endogenous interleukin-12 (IL-12) mediates protection against Yersinia
      enterocolitica in C57BL/6 mice by triggering gamma interferon (IFN-gamma)
      production in NK and CD4+ T cells. Administration of exogenous IL-12 confers
      protection against yersiniae in Yersinia-susceptible BALB/c mice but exacerbates
      yersiniosis in resistant C57BL/6 mice. Therefore, we wanted to dissect the
      different mechanisms exerted by IL-12 during Yersinia infections by using
      different models of Yersinia-resistant and -susceptible mice, including resistant
      C57BL/6 mice, susceptible BALB/c mice, intermediate-susceptible wild-type 129/Sv
      mice, 129/Sv IFN-gamma-receptor-deficient (IFN-gamma R-/-) mice and C57BL/6 tumor
      necrosis factor (TNF) receptor p55 chain-deficient (TNFR p55-/-) mice. IFN-gamma
      R-/- mice turned out to be highly susceptible to infection by Y. enterocolitica
      compared with IFN-gamma R+/+ mice. Administration of IL-12 was protective in IFN
      gamma R+/+ mice but not in IFN-gamma R-/- mice, suggesting that IFN-gamma R
      induced mechanisms are essential for IL-12-induced resistance against yersiniae.
      BALB/c mice could be rendered Yersinia resistant by administration of anti-CD4
      antibodies or by administration of IL-12. In contrast, C57BL/6 mice could be
      rendered more resistant by administration of transforming growth factor beta (TGF
      beta). Furthermore, IL-12-triggered toxic effects in C57BL/6 mice were abrogated
      by coadministration of TGF-beta. While administration of IL-12 alone increased
      TNF-alpha levels, administration of TGF-beta or TGF-beta plus IL-12 decreased
      both TNF-alpha and IFN-gamma levels in Yersinia-infected C57BL/6 mice. Moreover,
      IL-12 did not induce toxicity in Yersinia-infected TNFR p55-/- mice, suggesting
      that TNF-alpha accounts for IL-12-induced toxicity. Taken together, IL-12 may
      induce different effector mechanisms in BALB/c and C57BL/6 mice resulting either
      in protection or exacerbation. These results are important for understanding the
      critical balance of proinflammatory and regulatory cytokines in bacterial
      infections which is decisive for beneficial effects of cytokine therapy.

PMID- 9573111
TI  - Use of a Mycobacterium tuberculosis H37Rv bacterial artificial chromosome library
      for genome mapping, sequencing, and comparative genomics.
AB  - The bacterial artificial chromosome (BAC) cloning system is capable of stably
      propagating large, complex DNA inserts in Escherichia coli. As part of the
      Mycobacterium tuberculosis H37Rv genome sequencing project, a BAC library was
      constructed in the pBeloBAC11 vector and used for genome mapping, confirmation of
      sequence assembly, and sequencing. The library contains about 5,000 BAC clones,
      with inserts ranging in size from 25 to 104 kb, representing theoretically a 70
      fold coverage of the M. tuberculosis genome (4.4 Mb). A total of 840 sequences
      from the T7 and SP6 termini of 420 BACs were determined and compared to those of
      a partial genomic database. These sequences showed excellent correlation between
      the estimated sizes and positions of the BAC clones and the sizes and positions
      of previously sequenced cosmids and the resulting contigs. Many BAC clones
      represent linking clones between sequenced cosmids, allowing full coverage of the
      H37Rv chromosome, and they are now being shotgun sequenced in the framework of
      the H37Rv sequencing project. Also, no chimeric, deleted, or rearranged BAC
      clones were detected, which was of major importance for the correct mapping and
      assembly of the H37Rv sequence. The minimal overlapping set contains 68 unique
      BAC clones and spans the whole H37Rv chromosome with the exception of a single
      gap of approximately 150 kb. As a postgenomic application, the canonical BAC set
      was used in a comparative study to reveal chromosomal polymorphisms between M.
      tuberculosis, M. bovis, and M. bovis BCG Pasteur, and a novel 12.7-kb segment
      present in M. tuberculosis but absent from M. bovis and M. bovis BCG was
      characterized. This region contains a set of genes whose products show low
      similarity to proteins involved in polysaccharide biosynthesis. The H37Rv BAC
      library therefore provides us with a powerful tool both for the generation and
      confirmation of sequence data as well as for comparative genomics and other
      postgenomic applications. It represents a major resource for present and future
      M. tuberculosis research projects.

PMID- 9573112
TI  - Isolation of the third capsule-associated gene, CAP60, required for virulence in
      Cryptococcus neoformans.
AB  - A polysaccharide capsule is one of the most important virulence factors for the
      pathogenic fungus Cryptococcus neoformans. We previously characterized two
      capsule-associated genes, CAP59 and CAP64. To further dissect the molecular
      mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline
      1-oxide were obtained. The acapsular phenotype of one of these mutants was
      complemented. The cloned gene was designated CAP60, and deletion of this newly
      described capsule-associated gene resulted in an acapsular phenotype. The
      proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative
      transmembrane domain close to the N terminus. DNA sequence analysis revealed that
      CAP60 has similarity to CAP59 at the center portion of its coding regions.
      Contour-clamped homogeneous electric field blot analysis suggested that these two
      genes are on the same chromosome. CAP60 and CAP59, however, could not be
      functionally substituted for each other by direct complementation or by domain
      swap experiments. In addition, CAP60 is closely linked to a gene which is similar
      to a cellulose growth-specific gene of Agaricus bisporus, CEL1. Immunogold
      electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p
      was primarily localized to the nuclear membrane. Animal model studies indicated
      that CAP60 is essential for virulence. Thus, CAP60 is required for both capsule
      formation and virulence.

PMID- 9573113
TI  - The surface of Toxoplasma tachyzoites is dominated by a family of
      glycosylphosphatidylinositol-anchored antigens related to SAG1.
AB  - Toxoplasma gondii is an Apicomplexan parasite with a complex life cycle that
      includes a rapidly dividing asexual stage known as the tachyzoite. The tachyzoite
      surface has been reported to comprise five major antigens, the most abundant of
      which is designated SAG1 (for surface antigen 1). At least one of the other four
      (SAG3) and another recently described minor antigen (SRS1 [for SAG1-related
      sequence 1]) have previously been shown to be structurally related to SAG1. To
      determine if further SAG1 homologs exist, we searched a Toxoplasma expressed
      sequence tag (EST) database and found numerous ESTs corresponding to at least
      three new genes related to SAG1. Like SAG1, these new SRS genes encode apparently
      glycosylphosphatidylinositol-anchored proteins that share several motifs and a
      set of conserved cysteine residues. This family appears to have arisen by
      divergence from a common ancestor under selection for the conservation of overall
      topology. The products of two of these new genes (SRS2 and SRS3) are shown to be
      expressed on the surface of Toxoplasma tachyzoites by immunofluorescence. We also
      identified strain-specific differences in relative expression levels. A total of
      10 members of the SAG1 gene family have now been identified, which apparently
      include three of the five major surface antigens previously described and one
      antigen expressed only in bradyzoites. The function of this family may be to
      provide a redundant system of receptors for interaction with host cells and/or to
      direct the immune responses that limit acute T. gondii infections.

PMID- 9573114
TI  - The Legionella pneumophila icmGCDJBF genes are required for killing of human
      macrophages.
AB  - Previously, a collection of mutants of Legionella pneumophila that had lost the
      ability to multiply within and kill human macrophages was generated by
      Tn903dIIlacZ transposon mutagenesis and classified into DNA hybridization groups.
      A subset of these mutants was complemented by a plasmid, pMW100, containing a
      13.5-kb genomic DNA insert. This plasmid restored the ability to multiply within
      and produce cytopathic effects on human macrophages to members of DNA
      hybridization groups II, IV, VI, and XVII. A region of the genomic insert of
      pMW100 was sequenced, and eight potential genes were identified and named icmE,
      icmG, icmC, icmD, icmJ, icmB, icmF, and tphA. None of the genes encode potential
      protein products with significant homology to previously characterized proteins,
      except for tphA, whose product has significant homology to a family of
      metabolite/H+ symport proteins from gram-negative bacteria. The positions of the
      Tn903dIIlacZ insertions within the genes were determined by nucleotide
      sequencing. No Tn903dIIlacZ insertions mapped to icmG, icmJ, or tphA; therefore,
      these loci were mutated to test whether they were required for macrophage
      killing. Complementation analysis was used to evaluate the roles of the potential
      gene products and provide information on the organization of transcriptional
      units within the region. The results indicate that all identified open reading
      frames except tphA are required for killing of human macrophages.

PMID- 9573115
TI  - Identification and characterization of heparin binding regions of the Fim2
      subunit of Bordetella pertussis.
AB  - Bordetella pertussis fimbriae bind to sulfated sugars such as heparin through the
      major subunit Fim2. The Fim2 subunit contains two regions, designated H1 and H2,
      which show sequence similarity with heparin binding regions of fibronectin, and
      the role of these regions in heparin binding was investigated with maltose
      binding protein (MBP)-Fim2 fusion proteins. Deletion derivatives of MBP-Fim2
      showed that both regions are important for binding to heparin. The role of H2 in
      heparin binding was confirmed by site-directed mutagenesis in which basic amino
      acids were replaced by alanine. These studies revealed that Lys-186 and Lys-187
      are important for heparin binding of MBP-Fim2, whereas Arg-179 is not required.
      Peptides derived from H1 and H2 (pepH1 and pepH2) also showed heparin binding
      activity. Using a series of peptides, in each of which a different basic amino
      acid was substituted for alanine, we demonstrated that the structural
      requirements for heparin binding differ significantly among pepH1 and pepH2
      peptides. A Pepscan analysis of Fim2 revealed regions outside H1 and H2 which
      bind heparin and showed that not only basic amino acids but also tyrosines may be
      important for binding to sulfated sugars. A comparison of the heparin binding
      regions of Fim2 with homologous regions of Fim3 and FimX, two closely related but
      antigenically distinct fimbrial subunits, showed that basic amino acids and
      tyrosines are generally conserved. The major heparin binding regions identified
      in Fim2 are part of epitopes recognized by human antibodies, suggesting that the
      heparin binding regions are exposed at the fimbrial surface and are
      immunodominant. Since B. pertussis fimbriae show weak serological cross
      reactivity, the differences in primary structure in the heparin binding regions
      of Fim2, Fim3, and FimX may affect antibody binding but not heparin binding,
      allowing the bacteria to evade antibody-mediated immunity by switching the
      fimbrial gene expressed.

PMID- 9573116
TI  - Soluble CD14 activates monocytic cells independently of lipopolysaccharide.
AB  - The glycoprotein CD14 acts as a receptor for lipopolysaccharide (LPS), either
      when anchored in the myeloid cell membrane (mCD14) or as a soluble molecule
      (sCD14) in serum. sCD14-LPS complexes activate cells devoid of mCD14. However,
      the role of sCD14 independent of LPS is unknown. Therefore, the effect of sCD14
      on monocyte functions was investigated in the monocytic cell lines THP1 and Mono
      Mac 6 and in fresh human monocytes. Under serum-free conditions, endotoxin-free
      human recombinant sCD14(1-348), (rsCD14(1-348)) induced tumor necrosis factor
      alpha (TNF-alpha). The TNF-alpha effect was stronger in THP1 cells than in Mono
      Mac 6 cells or monocytes. It was dose dependent, with a maximum at 1 microg/ml,
      and time dependent, with a maximum after 2 h. sCD14 purified from urine had the
      same cytokine-activating capacity. In contrast, C-terminally truncated rsCD14(1
      152) was inactive. The rsCD14 effect was not due to LPS contamination, since it
      was resistant to polymyxin and lipid IVa but sensitive to heat and trypsin. The
      rsCD14-induced cytokine induction was blocked by preincubation of rsCD14 with a
      monoclonal anti-CD14 antibody that did not recognize the LPS-binding site.
      Release of the TNF-alpha disappeared upon pretreatment of rsCD14 in 50% plasma or
      in complete, heat-inactivated or sCD14-depleted serum. Moreover, cytokine
      production was no longer observed when rsCD14 was pretreated with thrombocytes.
      The thrombocyte effect was dose and time dependent. In conclusion, sCD14 is able
      to activate myeloid cells, and the effect is prevented by the presence of plasma,
      serum, or thrombocytes.

PMID- 9573117
TI  - Potential of a novel protein, OMP26, from nontypeable Haemophilus influenzae to
      enhance pulmonary clearance in a rat model.
AB  - A major outer membrane protein band of approximately 25 to 27 kDa is commonly
      observed in strains of Haemophilus influenzae. This study has investigated the
      potential of a 26-kDa protein (OMP26) from nontypeable H. influenzae (NTHI) as a
      vaccine candidate. OMP26 was used to immunize rats via intestinal Peyer's
      patches, followed by an intratracheal boost. Immunization was found to
      significantly enhance bacterial clearance following pulmonary challenge with both
      the homologous NTHI strain and a different NTHI strain. Significant levels of
      anti-OMP26 were found in the serum and bronchoalveolar lavage from immunized
      rats, and isotypes of immunoglobulin G (IgG) were also measured in serum.
      Analysis of IgG isotypes present in serum following OMP26-immunization suggest
      that predominantly a T-helper 1-type response was induced. The OMP26 protein was
      amino-terminally sequenced and found to have no homology with the P5 of H.
      influenzae type b P5 or the fimbrin protein of NTHI, both can migrate upon sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis at similar molecular masses
      but OMP26 has 100% homology with a segment of the H. influenzae Rd genome. The
      results of this study suggest that OMP26 may be a suitable vaccine candidate
      against NTHI infection and warrants continued investigation and characterization.

PMID- 9573118
TI  - Opsonic antibodies to the surface M protein of group A streptococci in pooled
      normal immunoglobulins (IVIG): potential impact on the clinical efficacy of IVIG
      therapy for severe invasive group A streptococcal infections.
AB  - The surface M protein of group A streptococci (GAS) is one of the major virulence
      factors for this pathogen. Antibodies to the M protein can facilitate
      opsonophagocytosis by phagocytic cells present in human blood. We investigated
      whether pooled normal immunoglobulin G (IVIG) contains antibodies that can
      opsonize and enhance the phagocytosis of type M1 strains of GAS and whether the
      levels of these antibodies vary for different IVIG preparations. We focused on
      the presence of anti-M1 antibodies because the M1T1 serotype accounts for the
      majority of recent invasive GAS clinical isolates in our surveillance studies.
      The level of anti-M1 antibodies in three commercial IVIG preparations was
      determined by enzyme-linked immunosorbent assay (ELISA), and the opsonic activity
      of these antibodies was determined by neutrophil-mediated opsonophagocytosis of a
      representative M1T1 isolate. High levels of opsonic anti-M1 antibodies were found
      in all IVIG preparations tested, and there was a good correlation between ELISA
      titers and opsonophagocytic activity. However, there was no significant
      difference in the levels of opsonic anti-M1 antibodies among the various IVIG
      preparations or lots tested. Adsorption of IVIG with M1T1 bacteria removed the
      anti-M1 opsonic activity, while the level of anti-M3 opsonophagocytosis was
      unchanged. Plasma was obtained from seven patients with streptococcal toxic shock
      syndrome who received IVIG therapy, and the level of anti-M1 antibodies was
      assessed before and after IVIG administration. A significant increase in the
      level of type M1-specific antibodies was found in the plasma of all patients who
      received IVIG therapy (P < 0.006). The results reveal another potential mechanism
      by which IVIG can ameliorate severe invasive group A streptococcal infections.

PMID- 9573119
TI  - Disruption of the cellular inflammatory response to Listeria monocytogenes
      infection in mice with disruptions in targeted genes.
AB  - The results of this study to dissect the nature of the acquired immune response
      to infection with Listeria monocytogenes in mice with targetted gene disruptions
      show that successful resolution of disease requires the essential presence of
      alphabeta T cells and the capacity to elaborate gamma interferon. In the absence
      of either of these entities, mice experience increasingly severe hepatitis and
      tissue necrosis and die within a few days. The data from this study support the
      hypothesis that the protective process is the efficient replacement of
      neutrophils in lesions by longer-lived mononuclear phagocytes; alphabeta-T-cell
      knockout mice died from progressive infection before neutrophil replacement could
      occur, whereas in gammadelta-T-cell-knockout mice this replacement process in the
      liver has previously been shown to be much slower. In the present study we
      attribute this delay to reduced production of the macrophage-attracting chemokine
      MCP-1 in the gammadelta-T-cell-knockout animals. These data further support the
      hypothesis that gammadelta T cells are important in controlling the inflammatory
      process rather than being essential to the expression of protection.

PMID- 9573120
TI  - Effects of the antioxidant alpha-lipoic acid on human umbilical vein endothelial
      cells infected with Rickettsia rickettsii.
AB  - Rickettsia rickettsii infection of endothelial cells is manifested in very
      distinctive changes in cell morphology, consisting of extensive dilatation of the
      membranes of the endoplasmic reticulum and outer nuclear envelope and blebbing of
      the plasma membrane, as seen by transmission electron microscopy (D. J.
      Silverman, Infect. Immun. 44:545-553, 1984). These changes in cellular
      architecture are thought to be due to oxidant-mediated cell injury, since their
      occurrence correlates with dramatic alterations in cellular metabolism,
      particularly with regard to antioxidant systems. In this study, it was shown that
      R. rickettsii infection of human umbilical vein endothelial cells resulted in a
      significant depletion of intracellular reduced glutathione (thiol) content at 72
      and 96 h and decreased glutathione peroxidase activity at 72 h postinfection.
      Infected cells displayed a dramatic increase in the concentration of
      intracellular peroxides by 72 h. Supplementation of the cell culture medium with
      100, 200, or 500 microM alpha-lipoic acid, a metabolic antioxidant, after
      inoculation with R. rickettsii restored the intracellular levels of thiols and
      glutathione peroxidase and reduced the intracellular peroxide levels in infected
      cells. These effects were dose dependent. Treated infected monolayers maintained
      better viability at 96 h after inoculation with R. rickettsii than did untreated
      infected cells. Moreover, supplementation of the cell culture medium with 100
      microM alpha-lipoic acid for 72 h after infection prevented the occurrence of
      morphological changes in the infected cells. The presence of 100 or 200 microM
      alpha-lipoic acid did not influence rickettsial growth in endothelial cells, nor
      did it affect the ability of R. rickettsii to form lytic plaques in Vero cells.
      Treatment with 500 microM alpha-lipoic acid decreased by 50% both the number and
      size of lytic plaques in Vero cells, and it also decreased the recovery of viable
      rickettsiae from endothelial cells. However, under all treatment conditions, a
      significant number of rickettsiae could be detected microscopically. Furthermore,
      the rickettsiae apparently retained their capacity for intracellular movement,
      since they possessed long polymerized actin tails after 72 and 96 h of treatment
      regardless of the concentration of alpha-lipoic acid used. Since alpha-lipoic
      acid does not seem to exhibit direct antirickettsial activity except with long
      term exposure at very high concentrations, the mechanism of its protective
      activity for endothelial cells infected with rickettsiae may involve complex
      changes in cellular metabolism that only indirectly affect rickettsiae.

PMID- 9573121
TI  - Essential role of gamma interferon in survival of colon ascendens stent
      peritonitis, a novel murine model of abdominal sepsis.
AB  - Despite considerable progress, peritonitis and sepsis remain life-threatening
      conditions. To improve the understanding of the pathophysiology encountered in
      sepsis, a new standardized and highly reproducible murine model of abdominal
      sepsis termed colon ascendens stent peritonitis (CASP) was developed. In CASP, a
      stent is inserted into the ascending colon, which generates a septic focus. CASP
      employing a stent of 14-gauge diameter (14G stent) results in a mortality of 100%
      within 18 to 48 h after surgery. By inserting stents of small diameters,
      mortality can be exactly controlled. Thus, CASP surgery with insertion of a 22G
      or 18G stent (22G or 18G CASP surgery) results in 38 or 68% mortality,
      respectively. 14G CASP surgery leads to a rapid invasion of bacteria into the
      peritoneum and the blood. As a consequence, endotoxemia occurs, inflammatory
      cells are recruited, and a systemic inflammatory response syndrome develops.
      Interestingly, the most pronounced upregulation of inflammatory cytokines (gamma
      interferon [IFN-gamma], tumor necrosis factor alpha [TNF-alpha] and interleukin
      12) is observed in spleen and lungs. CASP surgery followed by stent removal at
      specific time intervals revealed that all animals survived if intervention was
      performed after 3 h, whereas removal of the septic focus after 9 h did not
      prevent death, suggesting induction of autonomous mechanisms of a lethal
      inflammatory response syndrome. 18G CASP surgery in IFN-gamma receptor-deficient
      (IFNgammaR-/-) mice revealed an essential role of IFN-gamma in survival of
      sepsis, whereas TNF receptor p55-deficient (TNFRp55-/-) mice did not show altered
      survival rates. In summary, this study describes a novel animal model that
      closely mimics human sepsis and appears to be highly suitable for the study of
      the pathophysiology of abdominal sepsis. Importantly, this model demonstrates a
      protective role of IFN-gamma in survival of bacterial sepsis.

PMID- 9573122
TI  - Differential early interactions between Salmonella enterica serovar Typhi and two
      other pathogenic Salmonella serovars with intestinal epithelial cells.
AB  - Salmonella enterica serovar Typhi (hereafter referred to as S. typhi) is a host
      restricted pathogen that adheres to and invades the distal ileum and subsequently
      disseminates to cause typhoid fever in humans. However, S. typhi appears to be
      avirulent in small animals. In contrast, other pathogenic salmonellae, such as S.
      enterica serovars Typhimurium and Dublin (S. typhimurium and S. dublin,
      respectively), typically cause localized gastroenteritis in humans but have been
      used as models for typhoid fever because these organisms cause a disease in
      susceptible rodents that resembles human typhoid. In vivo, S. typhi has been
      demonstrated to attach to and invade murine M cells but is rapidly cleared from
      the Peyer's patches without destruction of the M cells. In contrast, invasion of
      M cells by S. typhimurium is accompanied by destruction of these M cells and
      subsequently sloughing of the epithelium. These data have furthered our view that
      the early steps in the pathogenesis of typhoidal and nontyphoidal Salmonella
      serovars are distinct. To extend this concept, we have utilized an in vitro model
      to evaluate three parameters of initial host-pathogen interactions: adherence of
      three Salmonella serovars to human and murine small intestinal epithelial cell
      (IEC) lines, the capacity of these salmonellae to invade IECs, and the ability of
      the bacteria to induce interleukin-6 (IL-6) in these cell lines as a measure of
      host cell activation and the host acute-phase response. The results demonstrate
      that S. typhi adheres to and invades human small IECs better than either S.
      typhimurium or S. dublin. Interestingly, invA and invE null mutants of S. typhi
      are able neither to adhere to nor to invade IECs, unlike S. typhimurium invA and
      invE mutants, which adhere to but cannot invade IECs. S. typhi also induces
      significantly greater quantities of IL-6 in human small IEC lines than either of
      the other two Salmonella serovars. These findings suggest that differential host
      cytokine responses to bacterial pathogens may play an important role in the
      pathological sequelae that follow infection. Importantly, S. typhimurium did not
      induce IL-6 in murine IECs. Since S. typhimurium infection in mice is often used
      as a model of typhoid fever, these findings suggest that, at least in this case,
      the mouse model does not reflect the human disease. Taken together, our studies
      indicate that (i) marked differences occur in the initial steps of S. typhi, S.
      typhimurium, and S. dublin pathogenesis, and (ii) conclusions about S. typhi
      pathogenesis that have been drawn from the mouse model of typhoid fever should be
      interpreted conservatively.

PMID- 9573123
TI  - Production of monocyte chemoattractant protein 1 in tuberculosis patients.
AB  - To investigate the role of monocyte chemoattractant protein 1 (MCP-1) in the
      immune response to Mycobacterium tuberculosis, we studied MCP-1 production in
      tuberculosis patients. CD14+ blood monocytes from tuberculosis patients
      spontaneously expressed higher levels of MCP-1 mRNA and protein than CD14+
      monocytes from healthy tuberculin reactors. MCP-1 production in lymph nodes from
      tuberculosis patients was also markedly increased. These findings suggest that
      MCP-1 can contribute to the antimycobacterial inflammatory response by attracting
      monocytes and T lymphocytes.

PMID- 9573124
TI  - Localization of Chlamydia trachomatis heat shock proteins 60 and 70 during
      infection of a human endometrial epithelial cell line in vitro.
AB  - Unlike chlamydial lipopolysaccharide, which is released from the developing
      inclusion to the surface of infected genital epithelial cells, both Chlamydia
      trachomatis heat shock protein (hsp) 60 and 70 antigens remained confined within
      the inclusion during the course of the chlamydial developmental cycle. Exposure
      of the infected cells to penicillin to induce a persistent infection or to a
      lipophilic microbicide did not potentiate secretion or exocytosis of the
      chlamydial hsp.

PMID- 9573125
TI  - A Neisseria meningitidis fbpABC mutant is incapable of using nonheme iron for
      growth.
AB  - The neisserial fbpABC locus has been proposed to act as an iron-specific ABC
      transporter system. To confirm this assigned function, we constructed an fbpABC
      mutant in Neisseria meningitidis by insertional inactivation of fbpABC with a
      selectable antibiotic marker. The mutant was unable to use iron supplied from
      human transferrin, human lactoferrin, or iron chelates. However, the use of iron
      from heme and human hemoglobin was unimpaired. These results support the
      obligatory participation of fbpABC in neisserial periplasmic iron transport and
      do not indicate a role for this genetic locus in the heme iron pathway.

PMID- 9573126
TI  - Construction and characterization of an isogenic slt-ii deletion mutant of
      enterohemorrhagic Escherichia coli.
AB  - Enterohemorrhagic Escherichia coli (EHEC) produces Shiga-like toxins (SLT),
      potent protein synthesis inhibitors. To further dissect the role of SLT-II in the
      course of disease, we have constructed E. coli TUV86-2, an isogenic SLT-II
      negative mutant of EHEC strain 86-24. The slt-ii gene was inactivated by suicide
      vector mutagenesis. We also isolated derivatives of strain 86-24 that were cured
      of the phage carrying the toxin genes.

PMID- 9573127
TI  - Protection against lethal murine coccidioidomycosis by a soluble vaccine from
      spherules.
AB  - The formaldehyde-killed, whole-spherule vaccine, which is protective against
      lethal challenge of laboratory animals with Coccidioides immitis, was
      fractionated. It yielded a soluble, multicomponent, subcellular fraction termed
      the 27K vaccine. This vaccine, when it was accompanied by adjuvant, protected
      mice against lethal intranasal and intravenous challenge with C. immitis.

PMID- 9573128
TI  - Proteins encoded by the cag pathogenicity island of Helicobacter pylori are
      required for NF-kappaB activation.
AB  - Helicobacter pylori is the etiological agent in the development of chronic
      gastritis, duodenal ulceration, and gastric adenocarcinoma. The difference in
      virulence between individual strains is reflected in their ability to induce
      interleukin-8 (IL-8) secretion from gastric epithelial cells. It has been shown
      that virulence is associated with the presence of a bacterial gene cluster (a
      pathogenicity island). We have recently demonstrated that H. pylori-mediated IL-8
      secretion requires activation of the transcription factor NF-kappaB. Here, we
      show that NF-kappaB induction requires six membrane proteins encoded within the
      pathogenicity island.

PMID- 9573129
TI  - Differential effects of gamma interferon on Chlamydia trachomatis growth in
      polarized and nonpolarized human epithelial cells in culture.
AB  - The effects of gamma interferon (IFN-gamma) on Chlamydia trachomatis growth in
      polarized epithelial cells were examined. The range of IFN-gamma concentrations
      causing aberrant chlamydial growth was wider in polarized than in nonpolarized
      cultures. Results indicate that chlamydial growth modulation in polarized cells
      readily leads to persistence and better reflects in vivo conditions.

PMID- 9573130
TI  - Chlamydia trachomatis infection of human mesothelial cells alters
      proinflammatory, procoagulant, and fibrinolytic responses.
AB  - In this study we demonstrate the capability of Chlamydia trachomatis to infect
      cultured human mesothelial cell (MC) monolayers and to induce the production of
      the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-8. Seventy-two
      hours after initial infection, both the procoagulant activity of MC and the
      activity of the fibrinolytic inhibitor (plasminogen activator inhibitor 1) in the
      supernatants were enhanced. These findings support the hypothesis that provoked
      proinflammatory responses contribute to the development of complications after
      chlamydial infection.

PMID- 9573131
TI  - Immunohistological localization of the MrkD adhesin in the type 3 fimbriae of
      Klebsiella pneumoniae.
AB  - The adhesive minor protein MrkD of the type 3 fimbria of Klebsiella pneumoniae
      was expressed and purified from Escherichia coli as a fusion protein with an N
      terminal polyhistidine tail. Polyclonal antibodies raised against MrkD
      specifically recognized the MrkD peptide in Western blots of fimbrial
      preparations. Immunoelectron microscopic analyses showed that the anti-MrkD
      immunoglobulins bound to the tip of the plasmid-encoded variant of the type 3
      fimbria of K. pneumoniae, whereas no binding to the chromosomally encoded MrkD
      deficient type 3 fimbrial variant of K. pneumoniae was detected. Immunoglobulins
      from an antiserum raised against purified type 3 fimbrial filaments bound
      laterally to both type 3 fimbrial variants. The anti-MrkD antibodies also bound
      to the tip of a papG deletion derivative of the E. coli P fimbria complemented
      with mrkD, indicating that MrkD structurally complements a PapG mutation in the P
      fimbria of E. coli.

PMID- 9573132
TI  - Clot formation by group A streptococci.
AB  - Group A streptococci of several different M serotypes can cause human plasma to
      clot in nutrient-poor media. Addition of glucose to the medium prevents clot
      formation. Once formed, clots are stable for several days and can be lysed on
      addition of exogenous streptokinase or urokinase. Clot lysis can also be achieved
      by addition of glucose to a clot containing wild-type group A streptococci but
      not clots containing an isogenic mutant in which the ska gene was inactivated.

PMID- 9573133
TI  - Lipoprotein(a) inhibits lipopolysaccharide-induced tumor necrosis factor alpha
      production by human mononuclear cells.
AB  - Lipoproteins can bind lipopolysaccharide (LPS) and decrease LPS-stimulated
      cytokine production. Lipoprotein(a) [Lp(a)] was as potent as low-density
      lipoproteins (LDL) in inhibiting LPS-stimulated tumor necrosis factor synthesis
      by human mononuclear cells. The kinetics of LPS inhibition by Lp(a) was similar
      to that of LDL. This suggests that circulating Lp(a) may be an important factor
      determining the amplitude of the response to LPS in humans.

PMID- 9573134
TI  - Roles for tumor necrosis factor and gamma interferon in resistance to enteric
      listeriosis.
AB  - Listeria monocytogenes normally infects the host by translocating from the
      intestinal lumen. Experiments were carried out to determine if, when, and where
      tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) function in
      antibacterial resistance during enteric listeriosis. Groups of normal mice and
      severe combined immunodeficient (SCID) mice were injected with neutralizing
      monoclonal antibodies (MAb) specific for each cytokine and then inoculated
      intragastrically with L. monocytogenes. The course of infection was monitored by
      enumerating listeriae in gut-associated lymphoid tissues, livers, and spleens. By
      the third day of infection, bacterial numbers in infected tissues and organs were
      greatly exacerbated in all mice treated with anti-TNF MAb, whereas bacterial
      numbers in the organs of mice treated with anti-IFN-gamma MAb did not differ from
      those present in the respective organs of control mice. However, by the fifth day
      of infection, bacterial numbers in the organs of anti-IFN-gamma MAb-treated
      normal mice and SCID mice were much greater than in the corresponding organs of
      control mice. Experiments with Listeria-immune mice revealed that TNF and IFN
      gamma are involved in the expression of anti-Listeria memory immunity; however,
      it was also found that the anti-IFN-gamma MAb was relatively ineffective in
      inhibiting the expression of anti-Listeria immunity, whereas a polyclonal anti
      IFN-gamma was quite effective.

PMID- 9573135
TI  - Lethal factor active-site mutations affect catalytic activity in vitro.
AB  - The lethal factor (LF) protein of Bacillus anthracis lethal toxin contains the
      thermolysin-like active-site and zinc-binding consensus motif HEXXH (K. R.
      Klimpel, N. Arora, and S. H. Leppla, Mol. Microbiol. 13:1093-1100, 1994). LF is
      hypothesized to act as a Zn2+ metalloprotease in the cytoplasm of macrophages,
      but no proteolytic activities have been previously shown on any target substrate.
      Here, synthetic peptides are hydrolyzed by LF in vitro. Mass spectroscopy and
      peptide sequencing of isolated cleavage products separated by reverse-phase high
      pressure liquid chromatography indicate that LF seems to prefer proline
      containing substrates. Substitution mutations within the consensus active-site
      residues completely abolish all in vitro catalytic functions, as does addition of
      1,10-phenanthroline, EDTA, and certain amino acid hydroxamates, including the
      novel zinc metalloprotease inhibitor ZINCOV. In contrast, the protease inhibitors
      bestatin and lysine CMK, previously shown to block LF activity on macrophages,
      did not block LF activity in vitro. These data provide the first direct evidence
      that LF may act as an endopeptidase.

PMID- 9573136
TI  - Cryptosporidium parvum infection of human intestinal xenografts in SCID mice
      induces production of human tumor necrosis factor alpha and interleukin-8.
AB  - The protozoan parasite Cryptosporidium parvum invades intestinal epithelial cells
      and can cause life-threatening diarrhea in immunocompromised individuals. Despite
      the clinical importance of this organism, much remains to be learned about the
      pathogenesis of C. parvum-induced diarrhea. To explore the role of the intestinal
      inflammatory response in C. parvum disease, using C. parvum oocysts we infected
      human intestinal xenografts in severe combined immunodeficient (SCID) mice. Seven
      days after infection, we found levels of human tumor necrosis factor alpha and
      interleukin-8 in C. parvum-infected human intestinal xenografts that were
      significantly higher than those seen in uninfected control xenografts. These
      results demonstrate that human intestinal cells produce proinflammatory cytokines
      in response to C. parvum infection and establish SCID-HU-INT mice as a model
      system to study the interactions of C. parvum with the human intestine.

PMID- 9573137
TI  - Control of ferredoxin and Gal/GalNAc lectin gene expression in Entamoeba
      histolytica by a cis-acting DNA sequence.
AB  - The ferredoxin (fdx) and lectin (hgl5) promoters of Entamoeba histolytica contain
      the DNA sequence motif TATTCTATT (URE3). Previously we showed that mutation of
      the URE3 motif in the hgl5 lectin promoter results in an increase in promoter
      reporter activity. Mutation of this motif in the fdx promoter led to a 40-to-50%
      decrease in fdx promoter activity as measured by reporter gene activity and
      abundance of mRNA. E. histolytica nuclear proteins exhibited sequence-specific
      binding to the URE3 motif in electrophoretic mobility shift assays. These results
      support the regulation of both ferredoxin and lectin promoters by a nuclear
      protein(s) which recognizes the URE3 motif.

PMID- 9573138
TI  - Virulent Brucella abortus prevents lysosome fusion and is distributed within
      autophagosome-like compartments.
AB  - Virulent and attenuated Brucella abortus strains attach to and penetrate
      nonprofessional phagocytic HeLa cells. Compared to pathogenic Brucella, the
      attenuated strain 19 hardly replicates within cells. The majority of the strain
      19 bacteria colocalized with the lysosome marker cathepsin D, suggesting that
      Brucella-containing phagosomes had fused with lysosomes, in which they may have
      degraded. The virulent bacteria prevented lysosome-phagosome fusion and were
      found distributed in the perinuclear region within compartments resembling
      autophagosomes.

PMID- 9573139
TI  - Gammadelta+ T cells preferentially respond to live rather than killed malaria
      parasites.
AB  - We have compared the in vitro responses of peripheral blood T cells from malaria
      unexposed donors to live Plasmodium falciparum schizonts, freeze-thawed schizont
      extracts (P. falciparum schizont extracts [PfSE]), and parasite culture
      supernatants. We show that the cells responding to PfSE and parasite culture
      supernatants are predominantly CD4+ TCR alphabeta+ while in the presence of live
      schizonts there is an additional activation of TCR gammadelta+ cells. Activation
      of TCR gammadelta+ cells in response to PfSE was seen only when irradiated
      autologous feeder cells or recombinant interleukin-2 (IL-2) was added to the
      cultures. Live schizonts but not PfSE induced significant IL-2 production in
      vitro in the first 5 days after stimulation, suggesting that induction of early
      IL-2 by live parasites may contribute to the marked activation of the TCR
      gammadelta+ population.

PMID- 9573140
TI  - Cloning of genes coding for the three subunits of thiocyanate hydrolase of
      Thiobacillus thioparus THI 115 and their evolutionary relationships to nitrile
      hydratase.
AB  - Thiocyanate hydrolase is a newly found enzyme from Thiobacillus thioparus THI 115
      that converts thiocyanate to carbonyl sulfide and ammonia (Y. Katayama, Y.
      Narahara, Y. Inoue, F. Amano, T. Kanagawa, and H. Kuraishi, J. Biol. Chem.
      267:9170-9175, 1992). We have cloned and sequenced the scn genes that encode the
      three subunits of the enzyme. The scnB, scnA, and scnC genes, arrayed in this
      order, contained open reading frames encoding sequences of 157, 126, and 243
      amino acid residues, respectively, for the beta, alpha, and gamma subunits,
      respectively. Each open reading frame was preceded by a typical Shine-Dalgarno
      sequence. The deduced amino-terminal peptide sequences for the three subunits
      were in fair agreement with the chemically determined sequences. The protein
      molecular mass calculated for each subunit was compatible with that determined by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From a computer
      analysis, thiocyanate hydrolase showed significant homologies to bacterial
      nitrile hydratases known to convert nitrile to the corresponding amide, which is
      further hydrolyzed by amidase to form acid and ammonia. The two enzymes were
      homologous over regions corresponding to almost the entire coding regions of the
      genes: the beta and alpha subunits of thiocyanate hydrolase were homologous to
      the amino- and carboxyl-terminal halves of the beta subunit of nitrile hydratase,
      and the gamma subunit of thiocyanate hydrolase was homologous to the alpha
      subunit of nitrile hydratase. Comparisons of the catalytic properties of the two
      homologous enzymes support the model for the reaction steps of thiocyanate
      hydrolase that was previously presented on the basis of biochemical analyses.

PMID- 9573141
TI  - Stimulation of transcription by mutations affecting conserved regions of RNA
      polymerase II.
AB  - Mutations that increase the low-level transcription of the Saccharomyces
      cerevisiae HIS4 gene, which results from deletion of the genes encoding
      transcription factors BAS1, BAS2, and GCN4, were isolated previously in SIT1
      (also known as RPO21, RPB1, and SUA8), the gene encoding the largest subunit of
      RNA polymerase II (RNAPII). Here we show that sit1 substitutions cluster in two
      conserved regions of the enzyme which form part of the active site. Six sit1
      mutations, affect region F, a region that is involved in transcriptional
      elongation and in resistance to alpha-aminatin. Four sit1 substitutions lie in
      another region involved in transcriptional elongation, region D, which binds Mg2+
      ions essential for RNA catalysis. One region D substitution is lethal unless
      suppressed by a substitution in region G and interacts genetically with PPR2, the
      gene encoding transcription elongation factor IIS. Some sit1 substitutions affect
      the selection of transcriptional start sites at the CYC1 promoter in a manner
      reminiscent of that of sua8 (sua stands for suppression of upstream ATG)
      mutations. Together with previous findings which indicate that regions D and G
      are in close proximity to the 3' end of the nascent transcript and that region F
      is involved in the translocation process, our results suggest that
      transcriptional activation by the sit1 mutations results from alteration of the
      RNAPII active center.

PMID- 9573142
TI  - Regulation of the carnitine pathway in Escherichia coli: investigation of the cai
      fix divergent promoter region.
AB  - The divergent structural operons caiTABCDE and fixABCX of Escherichia coli are
      required for anaerobic carnitine metabolism. Transcriptional monocopy lacZ fusion
      studies showed that both operons are coexpressed during anaerobic growth in the
      presence of carnitine, respond to common environmental stimuli (like glucose and
      nitrate), and are modulated positively by the same general regulators, CRP and
      FNR, and negatively by H-NS. Overproduction of the CaiF specific regulatory
      protein mediating the carnitine signal restored induction in an fnr mutant,
      corresponding to its role as the primary target for anaerobiosis. Transcript
      analysis identified two divergent transcription start points initiating 289 bp
      apart. DNase I footprinting revealed three sites with various affinities for the
      binding of the cAMP-CRP complex inside this regulatory region. Site-directed
      mutagenesis experiments indicated that previously reported perfect CRP motif 1,
      centered at -41.5 of the cai transcriptional start site, plays a direct role in
      the sole cai activation. In contrast, mutation in CRP site 2, positioned at -69.5
      of the fix promoter, caused only a threefold reduction in fix expression. Thus,
      the role of the third CRP site, located at -126.5 of fix, might be to reinforce
      the action of site 2. A critical 50-bp cis-acting sequence overlapping the fix
      mRNA start site was found, by deletion analysis, to be necessary for cai
      transcription. This region is thought to be involved in transduction of the
      signal mediated by the CaiF regulator.

PMID- 9573143
TI  - Genetic instability of the global regulator agr explains the phenotype of the xpr
      mutation in Staphylococcus aureus KSI9051.
AB  - Staphylococcus aureus KSI9051 has a complex mutation that was associated with the
      aberrant expression of cell surface and extracellular proteins (M. S. Smeltzer,
      M. E. Hart, and J. J. Iandolo, J. Bacteriol. 61:919-925, 1993). This mutation was
      named xpr, although no specific gene was identified. Here this mutation is
      referred to as Delta1058::Tn551. In this study, we show that in strain KSI9051,
      the Delta1058::Tn551 mutation occurred coincidentally with a frameshift in agrC
      that is expected to truncate the sensor component of the known staphylococcal
      global regulatory locus agr. Remarkably, pleiotropic mutations affecting cell
      surface and extracellular proteins are generated at frequencies approaching 50%
      upon the transduction of erythromycin resistance (Emr) encoded by
      Delta1058::Tn551 from S. aureus KSI905 back to its parental strain, S6C. Three
      independent isolates created in the manner of KSI9051 contained mutations within
      agrC. Each isolate had different mutations, suggesting that the transduction of
      Emr encoded by Delta1058::Tn551 affects the stability of agrC in S6C. In similar
      experiments with strains from an S. aureus 8325 genetic background, a mutant AgrC
      phenotype could not be isolated, implying that strain S6 has aberrant genetic
      behavior. A comparison of the nucleotide sequences of AgrC from several strains
      revealed seven errors in the GenBank entry for agr (X52543); these data were
      confirmed with plasmid pRN6650, the original wild-type clone of agr.

PMID- 9573144
TI  - Molecular and genetic analysis of two closely linked genes that encode,
      respectively, a protein phosphatase 1/2A/2B homolog and a protein kinase homolog
      in the cyanobacterium Anabaena sp. strain PCC 7120.
AB  - Reversible protein phosphorylation plays important roles in signal transduction.
      One gene, prpA, encoding a protein similar to eukaryotic types of phosphoprotein
      phosphatases PP1, PP2A, and PP2B, was cloned from the nitrogen-fixing
      cyanobacterium Anabaena sp. strain PCC 7120. Interestingly, a eukaryotic-type
      protein kinase gene, pknE, was found 301 bp downstream of prpA. This unusual
      genetic arrangement provides the opportunity for study about how the balance
      between protein phosphorylation and dephosphorylation can regulate cellular
      activities. Both proteins were overproduced in Escherichia coli and used to raise
      polyclonal antibodies. Immunodetection and RNA/DNA hybridization experiments
      suggest that these two genes are unlikely to be coexpressed, despite their close
      genetic linkage. PrpA is expressed constitutively under different nitrogen
      conditions, while PknE expression varies according to the nature of the nitrogen
      source. Inactivation analysis in vivo suggests that PrpA and PknE function to
      ensure a correct level of phosphorylation of the targets in order to regulate
      similar biological processes such as heterocyst structure formation and nitrogen
      fixation.

PMID- 9573145
TI  - The L-isoaspartyl protein repair methyltransferase enhances survival of aging
      Escherichia coli subjected to secondary environmental stresses.
AB  - Like its homologs throughout the biological world, the L-isoaspartyl protein
      repair methyltransferase of Escherichia coli, encoded by the pcm gene, can
      convert abnormal L-isoaspartyl residues in proteins (which form spontaneously
      from asparaginyl or aspartyl residues) to normal aspartyl residues. Mutations in
      pcm were reported to greatly reduce survival in stationary phase and when cells
      were subjected to heat or osmotic stresses (C. Li and S. Clarke, Proc. Natl.
      Acad. Sci. USA 89:9885-9889, 1992). However, we subsequently demonstrated that
      those strains had a secondary mutation in rpoS, which encodes a stationary-phase
      specific sigma factor (J. E. Visick and S. Clarke, J. Bacteriol. 179:4158-4163,
      1997). We now show that the rpoS mutation, resulting in a 90% decrease in HPII
      catalase activity, can account for the previously observed phenotypes. We further
      demonstrate that a new pcm mutant lacks these phenotypes. Interestingly, the
      newly constructed pcm mutant, when maintained in stationary phase for extended
      periods, is susceptible to environmental stresses, including exposure to
      methanol, oxygen radical generation by paraquat, high salt concentrations, and
      repeated heating to 42 degrees C. The pcm mutation also results in a competitive
      disadvantage in stationary-phase cells. All of these phenotypes can be
      complemented by a functional pcm gene integrated elsewhere in the chromosome.
      These data suggest that protein denaturation and isoaspartyl formation may act
      synergistically to the detriment of aging E. coli and that the repair
      methyltransferase can play a role in limiting the accumulation of the potentially
      disruptive isoaspartyl residues in vivo.

PMID- 9573146
TI  - The periplasmic cyclodextrin binding protein CymE from Klebsiella oxytoca and its
      role in maltodextrin and cyclodextrin transport.
AB  - Klebsiella oxytoca M5a1 has the capacity to transport and to metabolize alpha-,
      beta- and gamma-cyclodextrins. Cyclodextrin transport is mediated by the products
      of the cymE, cymF, cymG, cymD, and cymA genes, which are functionally homologous
      to the malE, malF, malG, malK, and lamB gene products of Escherichia coli. CymE,
      which is the periplasmic binding protein, has been overproduced and purified. By
      substrate-induced fluorescence quenching, the binding of ligands was analyzed.
      CymE bound alpha-cyclodextrin, beta-cyclodextrin, and gamma-cyclodextrin, with
      dissociation constants (Kd) of 0.02, 0.14 and 0.30 microM, respectively, and
      linear maltoheptaose, with a Kd of 70 microM. In transport experiments, alpha
      cyclodextrin was taken up by the cym system of K. oxytoca three to five times
      less efficiently than maltohexaose by the E. coli maltose system. Besides alpha
      cyclodextrin, maltohexaose was also taken up by the K. oxytoca cym system, but
      because of the inability of maltodextrins to induce the cym system, growth of E.
      coli mal mutants on linear maltodextrin was not observed when the cells harbored
      only the cym uptake system. Strains which gained this capacity by mutation could
      easily be selected, however.

PMID- 9573147
TI  - Identification and characterization of a new organic hydroperoxide resistance
      (ohr) gene with a novel pattern of oxidative stress regulation from Xanthomonas
      campestris pv. phaseoli.
AB  - We have isolated a new organic hydroperoxide resistance (ohr) gene from
      Xanthomonas campestris pv. phaseoli. This was done by complementation of an
      Escherichia coli alkyl hydroperoxide reductase mutant with an organic
      hydroperoxide-hypersensitive phenotype. ohr encodes a 14.5-kDa protein. Its amino
      acid sequence shows high homology with several proteins of unknown function. An
      ohr mutant was subsequently constructed, and it showed increased sensitivity to
      both growth-inhibitory and killing concentrations of organic hydroperoxides but
      not to either H2O2 or superoxide generators. No alterations in sensitivity to
      other oxidants or stresses were observed in the mutant. ohr had interesting
      expression patterns in response to low concentrations of oxidants. It was highly
      induced by organic hydroperoxides, weakly induced by H2O2, and not induced at all
      by a superoxide generator. The novel regulation pattern of ohr suggests the
      existence of a second organic hydroperoxide-inducible system that differs from
      the global peroxide regulator system, OxyR. Expression of ohr in various bacteria
      tested conferred increased resistance to tert-butyl hydroperoxide killing, but
      this was not so for wild-type Xanthomonas strains. The organic hydroperoxide
      hypersensitivity of ohr mutants could be fully complemented by expression of ohr
      or a combination of ahpC and ahpF and could be partially complemented by
      expression ahpC alone. The data suggested that Ohr was a new type of organic
      hydroperoxide detoxification protein.

PMID- 9573148
TI  - In vivo evidence that S-adenosylmethionine and fatty acid synthesis intermediates
      are the substrates for the LuxI family of autoinducer synthases.
AB  - Many gram-negative bacteria synthesize N-acyl homoserine lactone autoinducer
      molecules as quorum-sensing signals which act as cell density-dependent
      regulators of gene expression. We have investigated the in vivo source of the
      acyl chain and homoserine lactone components of the autoinducer synthesized by
      the LuxI homolog, TraI. In Escherichia coli, synthesis of N-(3
      oxooctanoyl)homoserine lactone by TraI was unaffected in a fadD mutant blocked in
      beta-oxidative fatty acid degradation. Also, conditions known to induce the fad
      regulon did not increase autoinducer synthesis. In contrast, cerulenin and
      diazoborine, specific inhibitors of fatty acid synthesis, both blocked
      autoinducer synthesis even in a strain dependent on beta-oxidative fatty acid
      degradation for growth. These data provide the first in vivo evidence that the
      acyl chains in autoinducers synthesized by LuxI-family synthases are derived from
      acyl-acyl carrier protein substrates rather than acyl coenzyme A substrates.
      Also, we show that decreased levels of intracellular S-adenosylmethionine caused
      by expression of bacteriophage T3 S-adenosylmethionine hydrolase result in a
      marked reduction in autoinducer synthesis, thus providing direct in vivo evidence
      that the homoserine lactone ring of LuxI-family autoinducers is derived from S
      adenosylmethionine.

PMID- 9573149
TI  - (Methyl)ammonium transport in the nitrogen-fixing bacterium Azospirillum
      brasilense.
AB  - An ammonium transporter of Azospirillum brasilense was characterized. In contrast
      to most previously reported putative prokaryotic NH4+ transporter genes, A.
      brasilense amtB is not part of an operon with glnB or glnZ which, in A.
      brasilense, encode nitrogen regulatory proteins PII and PZ, respectively.
      Sequence analysis predicts the presence of 12 transmembrane domains in the
      deduced AmtB protein and classifies AmtB as an integral membrane protein.
      Nitrogen regulates the transcription of the amtB gene in A. brasilense by the Ntr
      system. amtB is the first gene identified in A. brasilense whose expression is
      regulated by NtrC. The observation that ammonium uptake is still possible in
      mutants lacking the AmtB protein suggests the presence of a second NH4+ transport
      mechanism. Growth of amtB mutants at low ammonium concentrations is reduced
      compared to that of the wild type. This suggests that AmtB has a role in
      scavenging ammonium at low concentrations.

PMID- 9573150
TI  - Roles of DctA and DctB in signal detection by the dicarboxylic acid transport
      system of Rhizobium leguminosarum.
AB  - The dctA gene, coding for the dicarboxylate transport protein, has an inducible
      promoter dependent on activation by the two-component sensor-regulator pair DctB
      and DctD. LacZ fusion analysis indicates that there is a single promoter for dctB
      and dctD. The dctA promoter is also induced by nitrogen limitation, an effect
      that requires DctB-DctD and NtrC. DctB alone is able to detect dicarboxylates in
      the absence of DctA and initiate transcription via DctD. However, DctA modifies
      signal detection by DctB such that in the absence of DctA, the ligand specificity
      of DctB is broader. dctAp also responds to heterologous induction by osmotic
      stress in the absence of DctA. This effect requires both DctB and DctD. A
      transposon insertion in the dctA-dctB intergenic region (dctA101) which locks
      transcription of dctA at a constitutive level independent of DctB-DctD results in
      improper signalling by DctB-DctD. Strain RU150, which carries this insertion, is
      defective in nitrogen fixation (Fix-) and grows very poorly on ammonia as a
      nitrogen source whenever the DctB-DctD signalling circuit is activated by the
      presence of a dicarboxylate ligand. Mutation of dctB or dctD in strain RU150
      reinstates normal growth on dicarboxylates. This suggests that DctD-P improperly
      regulates a heterologous nitrogen-sensing operon. Increased expression of DctA,
      either via a plasmid or by chromosomal duplication, restores control of DctB-DctD
      and allows strain RU150 to grow on ammonia in the presence of a dicarboxylate.
      Thus, while DctB is a sensor for dicarboxylates in its own right, it is regulated
      by DctA. The absence of DctA allows DctB and DctD to become promiscuous with
      regard to signal detection and cross talk with other operons. This indicates that
      DctA contributes significantly to the signalling specificity of DctB-DctD and
      attenuates cross talk with other operons.

PMID- 9573151
TI  - The wzz (cld) protein in Escherichia coli: amino acid sequence variation
      determines O-antigen chain length specificity.
AB  - The O antigen is a polymer with a repeated unit. The chain length in most
      Escherichia coli strains has a modal value of 10 to 18 O units, but other strains
      have higher or lower modal values. wzz (cld/rol) mutants have a random chain
      length distribution, showing that the modal distribution is determined by the Wzz
      protein. Cloned wzz genes from E. coli strains with short (7 to 16), intermediate
      (10 to 18), and long (16 to 25) modal chain lengths were transferred to a model
      system, and their effects on O111 antigen were studied. The O111 chain length
      closely resembled that of the parent strains. We present data based on the
      construction of chimeric wzz genes and site-directed mutagenesis of the wzz gene
      to show that the modal value of O-antigen chain length of E. coli O1, O2, O7, and
      O157 strains can be changed by specific amino acid substitutions in wzz. It is
      concluded that the O-antigen chain length heterogeneity in E. coli strains is the
      result of amino acid sequence variation of the Wzz protein.

PMID- 9573152
TI  - Isolation and characterization of Methanobacterium thermoautotrophicum DeltaH
      mutants unable to grow under hydrogen-deprived conditions.
AB  - By using random mutagenesis and enrichment by chemostat culturing, we have
      developed mutants of Methanobacterium thermoautotrophicum that were unable to
      grow under hydrogen-deprived conditions. Physiological characterization showed
      that these mutants had poorer growth rates and growth yields than the wild-type
      strain. The mRNA levels of several key enzymes were lower than those in the wild
      type strain. A fed-batch study showed that the expression levels were related to
      the hydrogen supply. In one mutant strain, expression of both methyl coenzyme M
      reductase isoenzyme I and coenzyme F420-dependent 5,10
      methylenetetrahydromethanopterin dehydrogenase was impaired. The strain was also
      unable to form factor F390, lending support to the hypothesis that the factor
      functions in regulation of methanogenesis in response to changes in the
      availability of hydrogen.

PMID- 9573154
TI  - Identification of an Na+-dependent malonate transporter of Malonomonas rubra and
      its dependence on two separate genes.
AB  - Two membrane proteins encoded by the malonate fermentation gene cluster of
      Malonomonas rubra, MadL and MadM, have been synthesized in Escherichia coli. MadL
      and MadM were shown to function together as a malonate transport system, whereas
      each protein alone was unable to catalyze malonate transport. Malonate transport
      by MadLM is Na+ dependent, and imposition of a DeltapNa+ markedly enhanced the
      rate of malonate uptake. The kinetics of malonate uptake into E. coli BL21(DE3)
      cells synthesizing MadLM at different pH values indicated that Hmalonate- is the
      transported malonate species. The stimulation of malonate uptake by Na+ ions
      showed Michaelis-Menten kinetics, and a Km for Na+ of 1.2 mM was determined.
      These results suggest that MadLM is an electroneutral Na+/Hmalonate- symporter
      and that it is dependent on two separate genes.

PMID- 9573153
TI  - Negative regulation of IS2 transposition by the cyclic AMP (cAMP)-cAMP receptor
      protein complex.
AB  - Three sequences similar to that of the consensus binding sequence of the cyclic
      AMP (cAMP)-cAMP receptor protein (CRP) complex were found in the major IS2
      promoter region. Experiments were performed to determine whether the cAMP-CRP
      complex plays a role in the regulation of IS2 transposition. In the gel
      retardation assay, the cAMP-CRP complex was found to be able to bind the major
      IS2 promoter. A DNA footprinting assay confirmed that the cAMP-CRP complex binds
      to the sequences mentioned above. With an IS2 promoter-luciferase gene fusion
      construct, the cAMP-CRP complex was shown to inhibit transcription from the major
      IS2 promoter. IS2 was found to transpose at a frequency approximately 200-fold
      higher in an Escherichia coli host defective for CRP or adenyl cyclase than in a
      wild-type host. These results suggest that the cAMP-CRP complex is a negative
      regulator of IS2 transposition.

PMID- 9573155
TI  - In vitro and in vivo oxidation of methionine residues in small, acid-soluble
      spore proteins from Bacillus species.
AB  - Methionine residues in alpha/beta-type small, acid-soluble spore proteins (SASP)
      of Bacillus species were readily oxidized to methionine sulfoxide in vitro by t
      butyl hydroperoxide (tBHP) or hydrogen peroxide (H2O2). These oxidized alpha/beta
      type SASP no longer bound to DNA effectively, but DNA binding protected
      alpha/beta-type SASP against methionine oxidation by peroxides in vitro.
      Incubation of an oxidized alpha/beta-type SASP with peptidyl methionine sulfoxide
      reductase (MsrA), which can reduce methionine sulfoxide residues back to
      methionine, restored the alpha/beta-type SASP's ability to bind to DNA. Both tBHP
      and H2O2 caused some oxidation of the two methionine residues of an alpha/beta
      type SASP (SspC) in spores of Bacillus subtilis, although one methionine which is
      highly conserved in alpha/beta-type SASP was only oxidized to a small degree.
      However, much more methionine sulfoxide was generated by peroxide treatment of
      spores carrying a mutant form of SspC which has a lower affinity for DNA. MsrA
      activity was present in wild-type B. subtilis spores. However, msrA mutant spores
      were no more sensitive to H2O2 than were wild-type spores. The major mechanism
      operating for dealing with oxidative damage to alpha/beta-type SASP in spores is
      DNA binding, which protects the protein's methionine residues from oxidation both
      in vitro and in vivo. This may be important in vivo since alpha/beta-type SASP
      containing oxidized methionine residues no longer bind DNA well and alpha/beta
      type SASP-DNA binding is essential for long-term spore survival.

PMID- 9573156
TI  - Isolation and characterization of three Streptococcus pneumoniae transformation
      specific loci by use of a lacZ reporter insertion vector.
AB  - Although more than a dozen new proteins are produced when Streptococcus
      pneumoniae cells become competent for genetic transformation, only a few of the
      corresponding genes have been identified to date. To find genes responsible for
      the production of competence-specific proteins, a random lacZ transcriptional
      fusion library was constructed in S. pneumoniae by using the insertional lacZ
      reporter vector pEVP3. Screening the library for clones with competence-specific
      beta-galactosidase (beta-Gal) production yielded three insertion mutants with
      induced beta-Gal levels of about 4, 10, and 40 Miller units. In all three clones,
      activation of the lacZ reporter correlated with competence and depended on
      competence-stimulating peptide. Chromosomal loci adjacent to the integrated
      vector were subcloned from the insertion mutants, and their nucleotide sequences
      were determined. Genes at two of the loci exhibited strong similarity to parts of
      Bacillus subtilis com operons. One locus contained open reading frames (ORFs)
      homologous to the comEA and comEC genes in B. subtilis but lacked a comEB
      homolog. A second locus contained four ORFs with homology to the B. subtilis comG
      gene ORFs 1 to 4, but comG gene ORFs 5 to 7 were replaced in S. pneumoniae with
      an ORF encoding a protein homologous to transport ATP-binding proteins. Genes at
      all three loci were confirmed to be required for transformation by mutagenesis
      using pEVP3 for insertion duplications or an erm cassette for gene disruptions.

PMID- 9573157
TI  - Processed VirB2 is the major subunit of the promiscuous pilus of Agrobacterium
      tumefaciens.
AB  - Previous studies have implicated the obligatory requirement for the vir regulon
      (or "virulon") of the Ti plasmid for the transfer of oncogenes from Agrobacterium
      tumefaciens to plant cells. The machinery used in this horizontal gene transfer
      has been long thought to be a transformation or conjugative delivery system.
      Based on recent protein sequence comparisons, the proteins encoded by the virB
      operon are strikingly similar to proteins involved in the synthesis and assembly
      of conjugative pili such as the conjugative pilus of F plasmid in Escherichia
      coli. The F pilus is composed of TraA pilin subunits derived from TraA propilin.
      In the present study, evidence is provided showing that the counterpart of TraA
      is VirB2, which like TraA propilin is processed into a 7.2-kDa product that
      comprises the pilus subunit as demonstrated by biochemical and electron
      microscopic analyses. The processed VirB2 protein is present exocellularly on
      medium on which induced A. tumefaciens had grown and appears as thin filaments of
      10 nm that react specifically to VirB2 antibody. Exocellular VirB2 is produced
      abundantly at 19 degreesC as compared with 28 degreesC, an observation that
      parallels the effect of low temperature on the production of vir gene-specific
      pili observed previously (K. J. Fullner, L. C. Lara, and E. W. Nester, Science
      273:1107-1109, 1996). Export of the processed VirB2 requires other virB genes
      since mutations in these genes cause the loss of VirB2 pilus formation and result
      in processed VirB2 accumulation in the cell. The presence of exocellular
      processed VirB2 is directly correlated with the formation of pili, and it appears
      as the major protein in the purified pilus preparation. The evidence provides a
      compelling argument for VirB2 as the propilin whose 7.2-kDa processed product is
      the pilin subunit of the promiscuous conjugative pilus, hereafter called the "T
      pilus" of A. tumefaciens.

PMID- 9573158
TI  - Isolation of a periplasmic molecular chaperone-like protein of Rhodobacter
      sphaeroides f. sp. denitrificans that is homologous to the dipeptide transport
      protein DppA of Escherichia coli.
AB  - A periplasmic protein has been found to prevent aggregation of the acid-unfolded
      dimethyl sulfoxide reductase (DMSOR), the periplasmic terminal reductase of
      dimethyl sulfoxide respiration in the phototroph Rhodobacter sphaeroides f. sp.
      denitrificans, in a manner similar to that of the Escherichia coli chaperonin
      GroEL (Matsuzaki et al., Plant Cell Physiol. 37:333-339, 1996). The protein was
      isolated from the periplasm of the phototroph. It had a molecular mass of 58 kDa
      and had no subunits. The sequence of 14 amino-terminal residues of the protein
      was completely identical to that of the periplasmic dipeptide transport protein
      (DppA) of E. coli. The 58-kDa protein prevented aggregation to a degree
      comparable to that of GroEL on the basis of monomer protein. The 58-kDa protein
      also decreased aggregation of guanidine hydrochloride-denatured rhodanese, a
      mitochondrial matrix protein, during its refolding upon dilution. The 58-kDa
      protein is a kind of molecular chaperone and could be involved in maintaining
      unfolded DMSOR, after secretion of the latter into the periplasm, in a competent
      form for its correct folding.

PMID- 9573159
TI  - Interactions between the promoter regions of nitrogenase structural genes
      (nifHDK2) and DNA-binding proteins from N2- and ammonium-grown cells of the
      archaeon Methanosarcina barkeri 227.
AB  - Transcription initiation in Archaea (archaebacteria) resembles the eucaryotic
      process, having been shown to involve TATA box-like promoter regions as well as
      TATA-binding protein and TFIIB homologs. However, little is known about
      transcription regulation in archaea. We have previously demonstrated that
      transcripts of nifHDK2 genes, encoding Methanosarcina barkeri nitrogenase, are
      present in N2-grown cells but not in ammonium-grown cells, indicating that nif
      transcription is regulated by the nitrogen source. In this study, we detected
      proteins in M. barkeri cell extracts that bind specifically to DNA containing the
      putative promoter region of nifHDK2. No binding was found when the promoter
      region was deleted from the DNA. A competition assay showed that the methyl
      coenzyme M reductase (mcr) promoter region DNA and the nifH2 promoter region DNA
      competed for a common factor(s). There was no binding to the nifH2 promoter
      region by extracts of ammonium-grown cells, but there was binding by these
      extracts to promoter regions for mcr genes, which are presumably constitutively
      expressed. Interestingly, extracts of ammonium-grown cells inhibited binding to
      the nif promoter region by extracts of N2-grown cells. Fractionation of extracts
      of ammonium-grown cells with a heparin-Sepharose column resolved them into a
      fraction eluting at 0 M NaCl, which inhibited binding by extracts of N2-grown
      cells, and a fraction eluting at 0.5 to 0.75 M NaCl, which showed binding to the
      promoter region. These results are congruent with a model for regulation of nif
      gene expression in M. barkeri in which a substance present in ammonium-grown
      cells inhibits DNA binding by a transcription-associated protein or proteins.

PMID- 9573160
TI  - Function of protonatable residues in the flagellar motor of Escherichia coli: a
      critical role for Asp 32 of MotB.
AB  - Rotation of the bacterial flagellar motor is powered by a transmembrane gradient
      of protons or, in some species, sodium ions. The molecular mechanism of coupling
      between ion flow and motor rotation is not understood. The proteins most closely
      involved in motor rotation are MotA, MotB, and FliG. MotA and MotB are
      transmembrane proteins that function in transmembrane proton conduction and that
      are believed to form the stator. FliG is a soluble protein located on the
      cytoplasmic face of the rotor. Two other proteins, FliM and FliN, are known to
      bind to FliG and have also been suggested to be involved to some extent in torque
      generation. Proton (or sodium)-binding sites in the motor are likely to be
      important to its function and might be formed from the side chains of acidic
      residues. To investigate the role of acidic residues in the function of the
      flagellar motor, we mutated each of the conserved acidic residues in the five
      proteins that have been suggested to be involved in torque generation and
      measured the effects on motility. None of the conserved acidic residues of MotA,
      FliG, FliM, or FliN proved essential for torque generation. An acidic residue at
      position 32 of MotB did prove essential. Of 15 different substitutions studied at
      this position, only the conservative-replacement D32E mutant retained any
      function. Previous studies, together with additional data presented here,
      indicate that the proteins involved in motor rotation do not contain any
      conserved basic residues that are critical for motor rotation per se. We propose
      that Asp 32 of MotB functions as a proton-binding site in the bacterial flagellar
      motor and that no other conserved, protonatable residues function in this
      capacity.

PMID- 9573161
TI  - Joint transcriptional control of xpsR, the unusual signal integrator of the
      Ralstonia solanacearum virulence gene regulatory network, by a response regulator
      and a LysR-type transcriptional activator.
AB  - Ralstonia (Pseudomonas) solanacearum is a soil-borne phytopathogen that causes a
      wilting disease of many important crops. It makes large amounts of the
      exopolysaccharide EPS I, which it requires for efficient colonization, wilting,
      and killing of plants. Transcription of the eps operon, encoding biosynthetic
      enzymes for EPS I, is controlled by a unique and complex sensory network that
      responds to multiple environmental signals. This network is comprised of the
      novel transcriptional activator XpsR, three distinct two-component regulatory
      systems (VsrAD, VsrBC, and PhcSR), and the LysR-type regulator PhcA, which is
      under the control of PhcSR. Here we show that the xpsR promoter (PxpsR) is
      simultaneously controlled by PhcA and VsrD, permitting XpsR to act like a signal
      integrator, simultaneously coordinating signal input into the eps promoter from
      both VsrAD and PhcSR. Additionally, we used in vivo expression analysis and in
      vitro DNA binding assays with substitution and deletion mutants of PxpsR to show
      the following. (i) PhcA primarily interacts with a typical 14-bp LysR-type
      consensus sequence around position -77, causing a sixfold activation of PxpsR; a
      weaker, less-defined binding site between -183 and -239 likely enhances PhcA
      binding and activation via the -77 site another twofold. (ii) Full 70-fold
      activation of PxpsR requires the additional interaction of the VsrD response
      regulator (or its surrogate) with a 14-bp dyadic sequence centered around -315
      where it enhances activation (and possibly binding) by PhcA; however, VsrD alone
      cannot activate PxpsR. (iii) Increasing the distance between the putative VsrD
      binding site from that of PhcA by up to 232 bp did not dramatically affect PxpsR
      activation or regulation.

PMID- 9573162
TI  - An rRNA fragment and its antisense can alter decoding of genetic information.
AB  - rRNA plays a central role in protein synthesis and is intimately involved in the
      initiation, elongation, and termination stages of translation. However, the mode
      of its participation in these reactions, particularly as to the decoding of
      genetic information, remains elusive. In this paper, we describe a new approach
      that allowed us to identify an rRNA segment whose function is likely to be
      related to translation termination. By screening an expression library of random
      rRNA fragments, we identified a fragment of the Escherichia coli 23S rRNA
      (nucleotides 74 to 136) whose expression caused readthrough of UGA nonsense
      mutations in certain codon contexts in vivo. The antisense RNA fragment produced
      a similar effect, but in neither case was readthrough of UAA or UAG observed.
      Since termination at UGA in E. coli specifically requires release factor 2 (RF2),
      our data suggest that the fragments interfere with RF2-dependent termination.

PMID- 9573163
TI  - Unconventional genomic organization in the alpha subgroup of the Proteobacteria.
AB  - Pulsed-field gel electrophoresis was used to analyze the genomic organization of
      16 bacteria belonging or related to the family Rhizobiaceae of the alpha subgroup
      of the class Proteobacteria. The number and sizes of replicons were determined by
      separating nondigested DNA. Hybridization of an rrn gene probe was used to
      distinguish between chromosomes and plasmids. Members of the genus Agrobacterium
      all possess two chromosomes, and each biovar has a specific genome size. As
      previously demonstrated for Agrobacterium tumefaciens C58, the smaller
      chromosomes of Agrobacterium biovar 1 and Agrobacterium rubi strains appear to be
      linear. The genomes of Rhizobium strains were all of similar sizes but were seen
      to contain either one, two, or three megareplicons. Only one chromosome was
      present in the member of the related genus Phyllobacterium. We found one or two
      chromosomes in Rhodobacter and Brucella species, two chromosomes in Ochrobactrum
      anthropi, and one chromosome in Mycoplana dimorpha and Bartonella quintana; all
      of these genera are related to the Rhizobiaceae. The presence of multiple
      chromosomes is discussed from a phylogenetic and taxonomic point of view.

PMID- 9573164
TI  - Suppressor scanning at positions 177 and 236 in the Escherichia coli lactose/H+
      cotransporter and stereotypical effects of acidic substituents that suggest a
      favored orientation of transmembrane segments relative to the lipid bilayer.
AB  - Acidic substituents for Ala-177 (helix 6) or Tyr-236 (helix 7) in LacY cause
      effects on sugar recognition and cosubstrate coupling that are stereotypical of
      neutral substituents. Thus, helices 6 and 7 are probably oriented to produce
      little side-chain contact with the low dielectric lipid bilayer at positions 177
      and 236.

PMID- 9573165
TI  - Penicillin-binding protein 1 of Staphylococcus aureus is essential for growth.
AB  - pbpA, a gene encoding penicillin-binding protein (PBP) 1 of Staphylococcus
      aureus, was cloned in an Escherichia coli MC1061 transformant which grew on a
      plate containing 512 microg of vancomycin per ml. This gene encodes a 744-amino
      acid sequence which conserves three motifs of PBPs, SXXK, SXN, and KTG. The
      chromosomal copy of pbpA could be disrupted only when RN4220, a methicillin
      sensitive S. aureus strain, had additional copies of pbpA in its episome.
      Furthermore, these episomal copies of pbpA could not be eliminated by an
      incompatible plasmid when the chromosomal copy of pbpA was disrupted beforehand.
      Based on these observations, we concluded that pbpA is essential for the growth
      of methicillin-sensitive S. aureus.

PMID- 9573166
TI  - Role of alternative sigma factor algU in encystment of Azotobacter vinelandii.
AB  - Alginate is essential for encystment in Azotobacter vinelandii. Transcription of
      the algD gene, which codes for GDP-mannose dehydrogenase, a key enzyme in the
      alginate biosynthetic pathway, is initiated at two promoters, one of which, p2,
      has sigmaE consensus sequences. AlgU is the A. vinelandii alternative sigmaE
      factor. In this study, we constructed an algU mutant (SMU88) which, as expected,
      is impaired in alginate production, encystment, and transcription of the algD
      gene from the p2 promoter. Plasmid pJMSAT1, carrying the A. vinelandii algU gene,
      restored alginate production and encystment to SMU88 and to strain UW136, a
      naturally occurring algU mutant. Plasmid pSMU865, carrying the A. vinelandii
      mucABCD genes coding for negative regulators of AlgU activity and previously
      shown to diminish alginate production in the wild-type strain, ATCC 9046, was
      shown here to impair encystment and transcription of the algD gene from the p2
      algU-dependent promoter. Since nonencysting strain ATCC 9046/pSMU865 produced
      more alginate than some encysting strains, such as UW136/pJMSAT1, we propose an
      AlgU role in encystment, independent of the structural role that alginate plays
      in mature cysts.

PMID- 9573167
TI  - Acquired thermotolerance and temperature-induced protein accumulation in the
      extremely thermophilic bacterium Rhodothermus obamensis.
AB  - Temperature-induced changes in thermotolerance and protein composition were
      examined in heat-shocked cells and high-temperature-grown cells of the extremely
      thermophilic bacterium Rhodothermus obamensis. The survival at temperatures
      superoptimal for growth (90 and 95 degrees C) was enhanced in both heat-shocked
      cells and high-temperature-grown cells relative to that of cells grown at optimal
      temperatures. In a comparison of protein composition using two-dimensional gel
      electrophoresis, putative heat shock proteins (HSPs) and high-temperature growth
      specific proteins (HGPs) were detected. N-terminal amino acid sequence analysis
      revealed that the putative HSPs were quite similar to the ATP-binding subunits of
      ABC transporters and the HGPs were proteins corresponding to domains II and III
      of elongation factor Tu. These results suggested that this extreme thermophile
      has developed temperature-induced responses that include increased survival under
      hyperthermal conditions, changes in protein composition, and also the production
      of novel HSPs.

PMID- 9573168
TI  - Generation of Escherichia coli O9a serotype, a subtype of E. coli O9, by transfer
      of the wb* gene cluster of Klebsiella O3 into E. coli via recombination.
AB  - Genetic characterization of the wb* gene in a series of Escherichia coli and
      Klebsiella strains possessing the mannose homopolymer as the O-specific
      polysaccharide was carried out. The partial nucleotide sequences and PCR
      restriction fragment length polymorphism analysis suggested that E. coli serotype
      O9a, a subtype of E. coli O9, might have been generated by the insertion of the
      Klebsiella O3 wb* gene into a certain E. coli strain.

PMID- 9573169
TI  - Oligoribonuclease is encoded by a highly conserved gene in the 3'-5' exonuclease
      superfamily.
AB  - Oligoribonuclease, a 3'-to-5' exoribonuclease specific for small
      oligoribonucleotides, was purified to homogeneity from extracts of Escherichia
      coli. The purified protein is an alpha2 dimer of 40 kDa. NH2-terminal sequence
      analysis of the protein identified the gene encoding oligoribonuclease as yjeR
      (o204a), a previously reported open reading frame located at 94 min on the E.
      coli chromosome. However, as a consequence of the sequence information, the
      translation start site of this open reading frame has been revised. Cloning of
      yjeR led to overexpression of oligoribonuclease activity, and interruption of the
      cloned gene with a kanamycin resistance cassette eliminated the overexpression.
      On the basis of these data, we propose that yjeR be renamed orn. Orthologs of
      oligoribonuclease are present in a wide range of organisms, extending up to
      humans.

PMID- 9573170
TI  - Menaquinone (vitamin K2) biosynthesis: localization and characterization of the
      menA gene from Escherichia coli.
AB  - A key reaction in the biosynthesis of menaquinone involves the conversion of the
      soluble bicyclic naphthalenoid compound 1, 4-dihydroxy-2-naphthoic acid (DHNA) to
      the membrane-bound demethylmenaquinone. The enzyme catalyzing this reaction, DHNA
      octaprenyltransferase, attaches a 40-carbon side chain to DHNA. The menA gene
      encoding this enzyme has been cloned and localized to a 2.0-kb region of the
      Escherichia coli genome between cytR and glpK. DNA sequence analysis of the
      cloned insert revealed a 308-codon open reading frame (ORF), which by deletion
      analyses was shown to restore anaerobic growth of a menA mutant. Reverse-phase
      high-performance liquid chromatography analysis of quinones extracted from the
      orf-complemented cells independently confirmed the restoration of menaquinone
      biosynthesis, and similarly, analyses of isolated cell membranes for DHNA
      octaprenyltransferase activity confirmed the introduction of the menA product
      into the orf-complemented menA mutant. The validity of an ORF-associated putative
      promoter sequence was confirmed by primer extension analyses.

PMID- 9573171
TI  - Functional similarity between archaeal and bacterial CorA magnesium transporters.
AB  - The constitutively expressed CorA Mg2+ transporter is the major Mg2+ influx
      system of Salmonella typhimurium and Escherichia coli. Genomic sequence data
      indicated the presence of a homolog in the archaeal organism Methanococcus
      jannaschii. The putative M. jannaschii CorA was expressed in an Mg2+-transport
      deficient strain of S. typhimurium to determine its functional characteristics.
      The archaeal CorA homolog is a functional Mg2+ uptake system when expressed in S.
      typhimurium and has properties which are highly similar to those of the normal
      CorA transporter of S. typhimurium despite having a low level of sequence
      identity with the protein and being expressed in a lipid membrane of quite
      different composition than normal. This implies that the overall function of the
      proteins is the same and further suggests that their structures are very similar.

PMID- 9573173
TI  - Cloning and physical mapping of the EcoRI fragments of the giant linear plasmid
      SCP1.
AB  - A cosmid library was constructed for the 350-kb giant linear plasmid SCP1 and
      aligned on a successive linear map. Only a 0.8-kb gap has remained uncloned in
      the terminal inverted repeats close to both ends. Partial digestion of the
      aligned cosmids with EcoRI and hybridization with the flanking fragments of the
      vector enabled physical mapping of all of the EcoRI fragments. On this map, the
      methylenomycin biosynthetic gene cluster, the insertion sequence IS466, and the
      sapCDE genes coding for spore-associated proteins were localized.

PMID- 9573172
TI  - Mutational analysis of the phosphate-binding loop of Rhizobium meliloti DctD, a
      sigma54-dependent activator.
AB  - The phosphate-binding loop of sigma54-dependent activators is thought to
      participate in ATP binding and/or hydrolysis. Alanine substitutions at positions
      3, 4, 6, 7, and 8 of this motif in Rhizobium meliloti DctD disrupted
      transcriptional activation and ATP hydrolysis. Interestingly, substitution of
      alanine at position 7 also affected DNA binding.

PMID- 9573174
TI  - Regulation of lactose utilization genes in Staphylococcus xylosus.
AB  - The lactose utilization genes of Staphylococcus xylosus have been isolated and
      characterized. The system is comprised of two structural genes, lacP and lacH,
      encoding the lactose permease and the beta-galactosidase proteins, respectively,
      and a regulatory gene, lacR, coding for an activator of the AraC/XylS family. The
      lactose utilization genes are divergently arranged, the lacPH genes being
      opposite to lacR. The lacPH genes are cotranscribed from one promoter in front of
      lacP, whereas lacR is transcribed from two promoters of different strengths.
      Lactose transport as well as beta-galactosidase activity are inducible by the
      addition of lactose to the growth medium. Primer extension experiments
      demonstrated that regulation is achieved at the level of lacPH transcription
      initiation. Inducibility and efficient lacPH transcription are dependent on a
      functional lacR gene. Inactivation of lacR resulted in low and constitutive lacPH
      expression. Expression of lacR itself is practically constitutive, since
      transcription initiated at the major lacR promoter does not respond to the
      availability of lactose. Only the minor lacR promoter is lactose inducible. Apart
      from lactose-specific, LacR-dependent control, the lacPH promoter is also subject
      to carbon catabolite repression mediated by the catabolite control protein CcpA.
      When glucose is present in the growth medium, lacPH transcription initiation is
      reduced. Upon ccpA inactivation, repression at the lacPH promoter is relieved.
      Despite this loss of transcriptional regulation in the ccpA mutant strain, beta
      galactosidase activity is still reduced by glucose, suggesting another level of
      control.

PMID- 9573175
TI  - Metalloadsorption by Escherichia coli cells displaying yeast and mammalian
      metallothioneins anchored to the outer membrane protein LamB.
AB  - Yeast (CUP1) and mammalian (HMT-1A) metallothioneins (MTs) have been efficiently
      expressed in Escherichia coli as fusions to the outer membrane protein LamB. A 65
      amino-acid sequence from the CUP1 protein of Saccharomyces cerevisiae (yeast [Y]
      MT) was genetically inserted in permissive site 153 of the LamB sequence, which
      faces the outer medium. A second LamB fusion at position 153 was created with 66
      amino acids recruited from the form of human (H) MT that is predominant in the
      adipose tissue, HMT-1A. Both LamB153-YMT and LamB153-HMT hybrids were produced in
      vivo as full-length proteins, without any indication of instability or
      proteolytic degradation. Each of the two fusion proteins was functional as the
      port of entry of lambda phage variants, suggesting maintenance of the overall
      topology of the wild-type LamB. Expression of the hybrid proteins in vivo
      multiplied the natural ability of E. coli cells to bind Cd2+ 15- to 20-fold, in
      good correlation with the number of metal-binding centers contributed by the MT
      moiety of the fusions.

PMID- 9573176
TI  - Involvement of superoxide dismutase in spore coat assembly in Bacillus subtilis.
AB  - Endospores of Bacillus subtilis are enclosed in a proteinaceous coat which can be
      differentiated into a thick, striated outer layer and a thinner, lamellar inner
      layer. We found that the N-terminal sequence of a 25-kDa protein present in a
      preparation of spore coat proteins matched that of the Mn-dependent superoxide
      dismutase (SOD) encoded by the sod4 locus. sod4 is transcribed throughout the
      growth and sporulation of a wild-type strain and is responsible for the SOD
      activity detected in total cell extracts prepared from B. subtilis. Disruption of
      the sod4 locus produced a mutant that lacked any detectable SOD activity during
      vegetative growth and sporulation. The sodA mutant was not impaired in the
      ability to form heat- or lysozyme-resistant spores. However, examination of the
      coat layers of sodA mutant spores revealed increased extractability of the
      tyrosine-rich outer coat protein CotG. We showed that this condition was not
      accompanied by augmented transcription of the cotG gene in sporulating cells of
      the sodA mutant. We conclude that SodA is required for the assembly of CotG into
      the insoluble matrix of the spore and suggest that CotG is covalently cross
      linked into the insoluble matrix by an oxidative reaction dependent on SodA.
      Ultrastructural analysis revealed that the inner coat formed by a sodA mutant was
      incomplete. Moreover, the outer coat lacked the characteristic striated
      appearance of wild-type spores, a pattern that was accentuated in a cotG mutant.
      These observations suggest that the SodA-dependent formation of the insoluble
      matrix containing CotG is largely responsible for the striated appearance of this
      coat layer.

PMID- 9573177
TI  - The Pol beta-14 dominant negative rat DNA polymerase beta mutator mutant commits
      errors during the gap-filling step of base excision repair in Saccharomyces
      cerevisiae.
AB  - We demonstrated recently that dominant negative mutants of rat DNA polymerase
      beta (Pol beta) interfere with repair of alkylation damage in Saccharomyces
      cerevisiae. To identify the alkylation repair pathway that is disrupted by the
      Pol beta dominant negative mutants, we studied the epistatic relationship of the
      dominant negative Pol beta mutants to genes known to be involved in repair of DNA
      alkylation damage in S. cerevisiae. We demonstrate that the rat Pol beta mutants
      interfere with the base excision repair pathway in S. cerevisiae. In addition,
      expression of one of the Pol beta dominant negative mutants, Pol beta-14,
      increases the spontaneous mutation rate of S. cerevisiae whereas expression of
      another Pol beta dominant negative mutant, Pol beta-TR, does not. Expression of
      the Pol beta-14 mutant in cells lacking APN1 activity does not result in an
      increase in the spontaneous mutation rate. These results suggest that gaps are
      required for mutagenesis to occur in the presence of Pol beta-14 but that it is
      not merely the presence of a gap that results in mutagenesis. Our results suggest
      that mutagenesis can occur during the gap-filling step of base excision repair in
      vivo.

PMID- 9573178
TI  - Nucleotide sequence and spatiotemporal expression of the Vibrio cholerae vieSAB
      genes during infection.
AB  - The iviVII gene of Vibrio cholerae was previously identified by a screen for
      genes induced during intestinal infection. In the present study, nucleotide
      sequence analysis revealed that iviVII is a 1,659-bp open reading frame, herein
      designated vieB, that is predicted to be last in a tricistronic operon (vieSAB).
      The deduced amino acid sequence of VieS exhibited similarity to the sensor kinase
      component, and those of VieA and VieB were similar to the response regulator
      components, respectively, of the two-component signal transduction family.
      Analysis of transcriptional fusions to a site-specific DNA recombinase reporter,
      tnpR, revealed that vieS and vieA are transcribed during in vitro growth in a
      vieAB-independent and vieA-dependent manner, respectively. In contrast,
      transcription of vieB occurred exclusively during infection and was not dependent
      upon VieB. We conclude that the vieSAB genes are differentially regulated, at
      least during laboratory growth. Use of a V. cholerae strain harboring a
      vieB::tnpR transcriptional fusion allowed the kinetics and location of vieB
      expression within the intestine to be determined. We found that vieB
      transcription is induced shortly after infection of the proximal and mid-small
      intestine.

PMID- 9573179
TI  - S-layered Aneurinibacillus and Bacillus spp. are susceptible to the lytic action
      of Pseudomonas aeruginosa membrane vesicles.
AB  - When S-layered strains of Bacillus stearothermophilus and Aneurinibacillus
      thermoaerophilus, possessing S-layers of different lattice type and lattice
      constant as well as S-(glyco)protein chemistry, and isogenic S-layerless variants
      were subjected to membrane vesicles (MVs) from P. aeruginosa during plaque assays
      on plates or CFU measurements on cell suspensions, all bacterial types lysed.
      Electron microscopy of negative stains, thin sections, and immunogold-labelled MV
      preparations revealed that the vesicles adhered to all bacterial surfaces, broke
      open, and digested the underlying peptidoglycan-containing cell wall of all cell
      types. Reassembled S-layer did not appear to be affected by MVs, and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the S
      (glyco)proteins remained intact. meso-Diaminopimelic acid, as a peptidoglycan
      breakdown product, was found in all culture supernatants after MV attack These
      results suggest that even though MVs are much larger than the channels which
      penetrate these proteinaceous arrays, S-layers on gram-positive bacteria do not
      form a defensive barrier against the lytic action of MVs. The primary mode of
      attack is by the liberation from the MVs of a peptidoglycan hydrolase, which
      penetrates through the S-layer to digest the underlying peptidoglycan-containing
      cell wall. The S-layer is not affected by MV protease.

PMID- 9573180
TI  - Cloning, sequence analysis, and characterization of the genes involved in
      isoprimeverose metabolism in Lactobacillus pentosus.
AB  - Two genes, xylP and xylQ, from the xylose regulon of Lactobacillus pentosus were
      cloned and sequenced. Together with the repressor gene of the regulon, xylR, the
      xylPQ genes form an operon which is inducible by xylose and which is transcribed
      from a promoter located 145 bp upstream of xylP. A putative xylR binding site
      (xylO) and a cre-like element, mediating CcpA-dependent catabolite repression,
      were found in the promoter region. L. pentosus mutants in which both xylP and
      xylQ (LPE1) or only xylQ (LPE2) was inactivated retained the ability to ferment
      xylose but were impaired in their ability to ferment isoprimeverose (alpha-D
      xylopyranosyl-(1,6)-D-glucopyranose). Disruption of xylQ resulted specifically in
      the loss of a membrane-associated alpha-xylosidase activity when LPE1 or LPE2
      cells were grown on xylose. In the membrane fraction of wild-type bacteria, alpha
      xylosidase could catalyze the hydrolysis of isoprimeverose and p-nitrophenyl
      alpha-D-xylopyranoside with apparent Km and Vmax values of 0.2 mM and 446
      nmol/min/mg of protein, and 1.3 mM and 54 nmol/min/mg of protein, respectively.
      The enzyme could also hydrolyze the alpha-xylosidic linkage in xyloglucan
      oligosaccharides, but neither methyl-alpha-D-xylopyranoside nor alpha-glucosides
      were substrates. Glucose repressed the synthesis of alpha-xylosidase fivefold,
      and 80% of this repression was released in an L. pentosus delta ccpA mutant. The
      alpha-xylosidase gene was also expressed in the absence of xylose when xylR was
      disrupted.

PMID- 9573181
TI  - The 102-kilobase unstable region of Yersinia pestis comprises a high
      pathogenicity island linked to a pigmentation segment which undergoes internal
      rearrangement.
AB  - Several pathogenicity islands have recently been identified in different
      bacterial species, including a high-pathogenicity island (HPI) in Yersinia
      enterocolitica 1B. In Y. pestis, a 102-kb chromosomal fragment (pgm locus) that
      carries genes involved in iron acquisition and colony pigmentation can be deleted
      en bloc. In this study, characterization and mapping of the 102-kb region of Y.
      pestis 6/69 were performed to determine if this unstable region is a
      pathogenicity island. We found that the 102-kb region of Y. pestis is composed of
      two clearly distinct regions: an approximately 35-kb iron acquisition segment,
      which is an HPI per se, linked to an approximately 68-kb pigmentation segment.
      This linkage was preserved in all of the Y. pestis strains studied. However,
      several nonpigmented Y. pestis strains harboring an irp2 gene have been
      previously identified, suggesting that the pigmentation segment is independently
      mobile. Comparison of the physical map of the 102-kb region of these strains with
      that of strain 6/69 and complementation experiments were carried out to determine
      the genetic basis of this phenomenon. We demonstrate that several different
      mechanisms involving mutations and various-size deletions are responsible for the
      nonpigmented phenotype in the nine strains studied. However, no deletion
      corresponded exactly to the pigmentation segment. The 102-kb region of Y. pestis
      is an evolutionarily stable linkage of an HPI with a pigmentation segment in a
      region of the chromosome prone to rearrangement in vitro.

PMID- 9573182
TI  - 2-Ketocyclohexanecarboxyl coenzyme A hydrolase, the ring cleavage enzyme required
      for anaerobic benzoate degradation by Rhodopseudomonas palustris.
AB  - 2-Ketocyclohexanecarboxyl coenzyme A (2-ketochc-CoA) hydrolase has been proposed
      to catalyze an unusual hydrolytic ring cleavage reaction as the last unique step
      in the pathway of anaerobic benzoate degradation by bacteria. This enzyme was
      purified from the phototrophic bacterium Rhodopseudomonas palustris by sequential
      Q-Sepharose, phenyl-Sepharose, gel filtration, and hydroxyapatite chromatography.
      The sequence of the 25 N-terminal amino acids of the purified hydrolase was
      identical to the deduced amino acid sequence of the badI gene, which is located
      in a cluster of genes involved in anaerobic degradation of aromatic acids. The
      deduced amino acid sequence of badI indicates that 2-ketochc-CoA hydrolase is a
      member of the crotonase superfamily of proteins. Purified BadI had a molecular
      mass of 35 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and a native molecular mass of 134 kDa as determined by gel
      filtration. This indicates that the native form of the enzyme is a homotetramer.
      The purified enzyme was insensitive to oxygen and catalyzed the hydration of 2
      ketochc-CoA to yield pimelyl-CoA with a specific activity of 9.7 micromol min(-1)
      mg of protein(-1). Immunoblot analysis using polyclonal antiserum raised against
      the purified hydrolase showed that the synthesis of BadI is induced by growth on
      benzoate and other proposed benzoate pathway intermediates but not by growth on
      pimelate or succinate. An R. palustris mutant, carrying a chromosomal disruption
      of badI, did not grow with benzoate and other proposed benzoate pathway
      intermediates but had wild-type doubling times on pimelate and succinate. These
      data demonstrate that BadI, the 2-ketochc-CoA hydrolase, is essential for
      anaerobic benzoate metabolism by R. palustris.

PMID- 9573183
TI  - Substrate specificities of hybrid naphthalene and 2,4-dinitrotoluene dioxygenase
      enzyme systems.
AB  - Bacterial three-component dioxygenase systems consist of reductase and ferredoxin
      components which transfer electrons from NAD(P)H to a terminal oxygenase. In most
      cases, the oxygenase consists of two different subunits (alpha and beta). To
      assess the contributions of the alpha and beta subunits of the oxygenase to
      substrate specificity, hybrid dioxygenase enzymes were formed by coexpressing
      genes from two compatible plasmids in Escherichia coli. The activities of hybrid
      naphthalene and 2,4-dinitrotoluene dioxygenases containing four different beta
      subunits were tested with four substrates (indole, naphthalene, 2,4
      dinitrotoluene, and 2-nitrotoluene). In the active hybrids, replacement of small
      subunits affected the rate of product formation but had no effect on the
      substrate range, regiospecificity, or enantiomeric purity of oxidation products
      with the substrates tested. These studies indicate that the small subunit of the
      oxygenase is essential for activity but does not play a major role in determining
      the specificity of these enzymes.

PMID- 9573184
TI  - Control of 5',5'-dinucleoside triphosphate catabolism by APH1, a Saccharomyces
      cerevisiae analog of human FHIT.
AB  - The putative human tumor suppressor gene FHIT (fragile histidine triad) (M. Ohta
      et al., Cell 84:587-597, 1996) encodes a protein behaving in vitro as a
      dinucleoside 5',5"'-P1,P3-triphosphate (Ap3A) hydrolase. In this report, we show
      that the Saccharomyces cerevisiae APH1 gene product, which resembles human Fhit
      protein, also hydrolyzes dinucleoside 5',5'-polyphosphates, with Ap3A being the
      preferred substrate. Accordingly, disruption of the APH1 gene produced viable S.
      cerevisiae cells containing reduced Ap3A-hydrolyzing activity and a 30-fold
      elevated Ap3N concentration.

PMID- 9573186
TI  - Mutational analysis of the Chlamydia trachomatis rRNA P1 promoter defines four
      regions important for transcription in vitro.
AB  - We have characterized the Chlamydia trachomatis ribosomal promoter, rRNA P1, by
      measuring the effect of substitutions and deletions on in vitro transcription
      with partially purified C. trachomatis RNA polymerase. Our analyses indicate that
      rRNA P1 contains potential -10 and -35 elements, analogous to Escherichia coli
      promoters recognized by E-sigma70. We identified a novel AT-rich region
      immediately downstream of the -35 region. The effect of this region was specific
      for C. trachomatis RNA polymerase and strongly attenuated by single G or C
      substitutions. Upstream of the -35 region was an AT-rich sequence that enhanced
      transcription by C. trachomatis and E. coli RNA polymerases. We propose that this
      region functions as an UP element.

PMID- 9573185
TI  - Molecular evolution of Mycoplasma capricolum subsp. capripneumoniae strains,
      based on polymorphisms in the 16S rRNA genes.
AB  - Mycoplasma capricolum subsp. capripneumoniae belongs to the so-called Mycoplasma
      mycoides cluster and is the causal agent of contagious caprine pleuropneumonia
      (CCPP). All members of the M. mycoides cluster have two rRNA operons. The
      sequences of the 16S rRNA genes of both rRNA operons from 20 strains of M.
      capricolum subsp. capripneumoniae of different geographical origins in Africa and
      Asia were determined. Nucleotide differences which were present in only one of
      the two operons (polymorphisms) were detected in 24 positions. The polymorphisms
      were not randomly distributed in the 16S rRNA genes, and some of them were found
      in regions of low evolutionary variability. Interestingly, 11 polymorphisms were
      found in all the M. capricolum subsp. capripneumoniae strains, thus defining a
      putative ancestor. A sequence length difference between the 16S rRNA genes in a
      poly(A) region and 12 additional polymorphisms were found in only one or some of
      the strains. A phylogenetic tree was constructed by comparative analysis of the
      polymorphisms, and this tree revealed two distinct lines of descent. The
      nucleotide substitution rate of strains within line II was up to 50% higher than
      within line I. A tree was also constructed from individual operonal 16S rRNA
      sequences, and the sequences of the two operons were found to form two distinct
      clades. The topologies of both clades were strikingly similar, which supports the
      use of 16S rRNA sequence data from homologous operons for phylogenetic studies.
      The strain-specific polymorphism patterns of the 16S rRNA genes of M. capricolum
      subsp. capripneumoniae may be used as epidemiological markers for CCPP.

PMID- 9573187
TI  - Transcriptional repression mediated by LysR-type regulator CatR bound at multiple
      binding sites.
AB  - The catBCA operon of Pseudomonas putida encodes enzymes involved in the
      catabolism of benzoate. Transcription of this operon requires the LysR-type
      transcriptional regulator CatR and an inducer molecule, cis,cis-muconate.
      Previous gel shift assays and DNase I footprinting have demonstrated that CatR
      occupies two adjacent sites proximal to the catBCA promoter in the presence of
      the inducer. We report the presence of an additional binding site for CatR
      downstream of the catBCA promoter within the catB structural gene. This site,
      called the internal binding site (IBS), extends from +162 to +193 with respect to
      the catB transcriptional start site and lies within the catB open reading frame.
      Gel shift analysis and DNase I footprinting determined that CatR binds to this
      site with low affinity. CatR binds cooperatively with higher affinity to the IBS
      in the presence of the two upstream binding sites. Parallel in vivo and in vitro
      studies were conducted to determine the role of the internal binding site. We
      measured beta-galactosidase activity of catB-lacZ transcriptional fusions in
      vivo. Our results suggest a probable cis-acting repressor function for the
      internal binding site. Site-directed mutagenesis of the IBS verified this
      finding. The location of the IBS within the catB structural gene, the
      cooperativity observed in footprinting studies, and phasing studies suggest that
      the IBS likely participates in the interaction of CatR with the upstream binding
      sites by looping out the intervening DNA.

PMID- 9573188
TI  - Cloning and characterization of a gene encoding the major surface protein of the
      bacterial endosymbiont Wolbachia pipientis.
AB  - The maternally inherited intracellular symbiont Wolbachia pipientis is well known
      for inducing a variety of reproductive abnormalities in the diverse arthropod
      hosts it infects. It has been implicated in causing cytoplasmic incompatibility,
      parthenogenesis, and the feminization of genetic males in different hosts. The
      molecular mechanisms by which this fastidious intracellular bacterium causes
      these reproductive and developmental abnormalities have not yet been determined.
      In this paper, we report on (i) the purification of one of the most abundantly
      expressed Wolbachia proteins from infected Drosophila eggs and (ii) the
      subsequent cloning and characterization of the gene (wsp) that encodes it. The
      functionality of the wsp promoter region was also successfully tested in
      Escherichia coli. Comparison of sequences of this gene from different strains of
      Wolbachia revealed a high level of variability. This sequence variation
      correlated with the ability of certain Wolbachia strains to induce or rescue the
      cytoplasmic incompatibility phenotype in infected insects. As such, this gene
      will be a very useful tool for Wolbachia strain typing and phylogenetic analysis,
      as well as understanding the molecular basis of the interaction of Wolbachia with
      its host.

PMID- 9573189
TI  - The Streptomyces peucetius dpsY and dnrX genes govern early and late steps of
      daunorubicin and doxorubicin biosynthesis.
AB  - The Streptomyces peucetius dpsY and dnrX genes govern early and late steps in the
      biosynthesis of the clinically valuable antitumor drugs daunorubicin (DNR) and
      doxorubicin (DXR). Although their deduced products resemble those of genes
      thought to be involved in antibiotic production in several other bacteria, this
      information could not be used to identify the functions of dpsY and dnrX.
      Replacement of dpsY with a mutant form disrupted by insertion of the aphII
      neomycin-kanamycin resistance gene resulted in the accumulation of UWM5, the C-19
      ethyl homolog of SEK43, a known shunt product of iterative polyketide synthases
      involved in the biosynthesis of aromatic polyketides. Hence, DpsY must act along
      with the other components of the DNR-DXR polyketide synthase to form 12
      deoxyaklanonic acid, the earliest known intermediate of the DXR pathway. Mutation
      of dnrX in the same way resulted in a threefold increase in DXR production and
      the disappearance of two acid-sensitive, unknown compounds from culture extracts.
      These results suggest that dnrX, analogous to the role of the S. peucetius dnrH
      gene (C. Scotti and C. R. Hutchinson, J. Bacteriol. 178:73167321, 1996), may be
      involved in the metabolism of DNR and/or DXR to acid-sensitive compounds,
      possibly related to the baumycins found in many DNR-producing bacteria.

PMID- 9573190
TI  - Ferric citrate transport of Escherichia coli: functional regions of the FecR
      transmembrane regulatory protein.
AB  - Transcription of the ferric citrate transport genes of Escherichia coli is
      induced by ferric citrate bound to the outer membrane receptor FecA. Additional
      ferric citrate-specific regulatory proteins are FecR in the cytoplasmic membrane
      and the FecI sigma factor in the cytoplasm. To further understand the assumed
      FecR-mediated signal transduction across the cytoplasmic membrane, the
      transmembrane topology of FecR (317 amino acids) was determined with hybrid
      proteins containing portions of FecR and mature BlaM beta-lactamase. BlaM fused
      to FecR regions extending from residues 107 to 149 and residues 230 to 259
      conferred high ampicillin resistance to cells, while BlaM fused to sites between
      residues 159 and 210 and between residues 265 and 301 conferred low resistance.
      Cells that synthesized FecR'-BlaM with fusion joints between residues 8 and 81 of
      FecR were fully sensitive to ampicillin. The ampicillin resistance of the low
      resistance FecR'-BlaM hybrids was increased 2- to 10-fold by cosynthesis of
      plasmid-encoded GroEL GroES and SecB chaperones and in degP and ompT protease
      mutants, which suggested that the decreased ampicillin resistance level of these
      hybrids was caused by the formation of inclusion bodies and proteolytic
      degradation. Replacement of glycine by aspartate residues in the only hydrophobic
      FecR sequence (residues 85 to 100) abolished the beta-lactamase activity of high
      resistance FecR'-BlaM proteins, indicating that there are no other transmembrane
      regions in FecR that translocate BlaM into the periplasm independent of the
      hydrophobic sequence. All FecR'-BlaM proteins with at least 61 FecR residues
      complemented a fecR mutant such that it could grow on ferric citrate as the sole
      iron source and induced fecA-lacZ transcription independent of ferric citrate.
      The low resistance mediated by two FecR'-BlaM proteins in a fecA deletion mutant
      was increased 20-fold by transformation with a fecA-encoding plasmid. We propose
      that FecR spans the cytoplasmic membrane once, interacts in the periplasm with
      its C-terminal region with FecA occupied by ferric citrate, and transmits the
      information through the cytoplasmic membrane into the cytoplasm, where it
      converts FecI into an active sigma factor.

PMID- 9573191
TI  - Promoter selectivity of the Bradyrhizobium japonicum RpoH transcription factors
      in vivo and in vitro.
AB  - Expression of the dnaKJ and groESL1 heat shock operons of Bradyrhizobium
      japonicum depends on a sigma32-like transcription factor. Three such factors
      (RpoH1, RpoH2, and RpoH3) have previously been identified in this organism. We
      report here that they direct transcription from some but not all sigma32-type
      promoters when the respective rpoH genes are expressed in Escherichia coli. All
      three RpoH factors were purified as soluble C-terminally histidine-tagged
      proteins, although the bulk of overproduced RpoH3 was insoluble. The purified
      proteins were recognized by an anti-E. coli sigma32 serum. While RpoH1 and RpoH2
      productively interacted with E. coli core RNA polymerase and produced E. coli
      groE transcript in vitro, RpoH3 was unable to do so. B. japonicum core RNA
      polymerase was prepared and reconstituted with the RpoH proteins. Again, RpoH1
      and RpoH2 were active, and they initiated transcription at the B. japonicum
      groESL1 and dnaKJ promoters. In all cases, the in vitro start site was shown to
      be identical to the start site determined in vivo. Promoter competition
      experiments revealed that the B. japonicum dnaKJ and groESL1 promoters were
      suboptimal for transcription by RpoH1- or RpoH2-containing RNA polymerase from B.
      japonicum. In a mixture of different templates, the E. coli groESL promoter was
      preferred over any other promoter. Differences were observed in the specificities
      of both sigma factors toward B. japonicum rpoH-dependent promoters. We conclude
      that the primary function of RpoH2 is to supply the cell with DnaKJ under normal
      growth conditions whereas RpoH1 is responsible mainly for increasing the level of
      GroESL1 after a heat shock.

PMID- 9573192
TI  - Regulatory conservation and divergence of sigma32 homologs from gram-negative
      bacteria: Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and
      Agrobacterium tumefaciens.
AB  - The heat shock response in Escherichia coli is mediated primarily by the rpoH
      gene, encoding sigma32, which is specifically required for transcription of heat
      shock genes. A number of sigma32 homologs have recently been cloned from gram
      negative bacteria that belong to the gamma or alpha subdivisions of the
      proteobacteria. We report here some of the regulatory features of several such
      homologs (RpoH) expressed in E. coli as well as in respective cognate bacteria.
      When expressed in an E. coli delta rpoH strain lacking its own sigma32, these
      homologs activated the transcription of heat shock genes (groE and dnaK) from the
      start sites normally used in E. coli. The level of RpoH in Serratia marcescens
      and Pseudomonas aeruginosa cells was very low at 30 degrees C but was elevated
      markedly upon a shift to 42 degrees C, as found previously with E. coli. The
      increased RpoH levels upon heat shock resulted from both increased synthesis and
      stabilization of the normally unstable RpoH protein. In contrast, the RpoH level
      in Proteus mirabilis was relatively high at 30 degrees C and increased less
      markedly upon heat shock, mostly by increased synthesis; this sigma32 homolog was
      already stable at 30 degrees C, and little further stabilization occurred upon
      the shift to 42 degrees C. The increased synthesis of RpoH homologs in all these
      gamma proteobacteria was observed even in the presence of rifampin, suggesting
      that the induction occurred at the level of translation. Thus, the basic
      regulatory strategy of the heat shock response by enhancing the RpoH level is
      well conserved in the gamma proteobacteria, but some divergence in the actual
      mechanisms used occurred during evolution.

PMID- 9573193
TI  - A low pH-inducible, PhoPQ-dependent acid tolerance response protects Salmonella
      typhimurium against inorganic acid stress.
AB  - The acid tolerance response enables Salmonella typhimurium to survive exposures
      to potentially lethal acidic environments. The acid stress imposed in a typical
      assay for acid tolerance (log-phase cells in minimal glucose medium) was shown to
      comprise both inorganic (i.e., low pH) and organic acid components. A gene
      previously determined to affect acid tolerance, atbR, was identified as pgi, the
      gene encoding phosphoglucoisomerase. Mutations in pgi were shown to increase acid
      tolerance by preventing the synthesis of organic acids. Protocols designed to
      separate the stresses of inorganic from organic acids revealed that the
      regulators sigma38 (RpoS), Fur, and Ada have major effects on tolerance to
      organic acid stress but only minor effects on inorganic acid stress. In contrast,
      the two-component regulatory system PhoP (identified as acid shock protein ASP29)
      and PhoQ proved to be important for tolerance to inorganic [corrected] acid
      stress but had little effect against organic acid stress. PhoP mutants also
      failed to induce four ASPs, confirming a role for this regulator in acid
      tolerance. Acid shock induction of PhoP appears to occur at the transcriptional
      level and requires the PhoPQ system. Furthermore, induction by acid occurs even
      in the presence of high concentrations of magnesium, the ion known to be sensed
      by PhoQ. These results suggest that PhoQ can sense both Mg2+ and pH. Since phoP
      mutants are avirulent, the low pH activation of this system has important
      implications concerning the pathogenesis of S. typhimurium. The involvement of
      four regulators, two of which are implicated in virulence, underscores the
      complexity of the acid tolerance stress response and further suggests that
      features of acid tolerance and virulence are interwoven.

PMID- 9573194
TI  - Structure and expression of the FlaA periplasmic flagellar protein of Borrelia
      burgdorferi.
AB  - The spirochete which causes Lyme disease, Borrelia burgdorferi, has many features
      common to other spirochete species. Outermost is a membrane sheath, and within
      this sheath are the cell cylinder and periplasmic flagella (PFs). The PFs are
      subterminally attached to the cell cylinder and overlap in the center of the
      cell. Most descriptions of the B. burgdorferi flagellar filaments indicate that
      these organelles consist of only one flagellin protein (FlaB). In contrast, the
      PFs from other spirochete species are comprised of an outer layer of FlaA and a
      core of FlaB. We recently found that a flaA homolog was expressed in B.
      burgdorferi and that it mapped in a fla/che operon. These results led us to
      analyze the PFs and FlaA of B. burgdorferi in detail. Using Triton X-100 to
      remove the outer membrane and isolate the PFs, we found that the 38.0-kDa FlaA
      protein purified with the PFs in association with the 41.0-kDa FlaB protein. On
      the other hand, purifying the PFs by using Sarkosyl resulted in no FlaA in the
      isolated PFs. Sarkosyl has been used by others to purify B. burgdorferi PFs, and
      our results explain in part their failure to find FlaA. Unlike other spirochetes,
      B. burgdorferi FlaA was expressed at a lower level than FlaB. In characterizing
      FlaA, we found that it was posttranslationally modified by glycosylation, and
      thus it resembles its counterpart from Serpulina hyodysenteriae. We also tested
      if FlaA was synthesized in a spontaneously occurring PF mutant of B. burgdorferi
      (HB19Fla-). Although this mutant still synthesized flaA message in amounts
      similar to the wild-type amounts, it failed to synthesize FlaA protein. These
      results suggest that, in agreement with data found for FlaB and other spirochete
      flagellar proteins, FlaA is likely to be regulated on the translational level.
      Western blot analysis using Treponema pallidum anti-FlaA serum indicated that
      FlaA was antigenically well conserved in several spirochete species. Taken
      together, the results indicate that both FlaA and FlaB comprise the PFs of B.
      burgdorferi and that they are regulated differently from flagellin proteins of
      other bacteria.

PMID- 9573195
TI  - Activation of the proprotein transcription factor pro-sigmaE is associated with
      its progression through three patterns of subcellular localization during
      sporulation in Bacillus subtilis.
AB  - The activity of the sporulation transcription factor sigmaE in Bacillus subtilis
      is governed by an intercellular signal transduction pathway that controls the
      conversion of the inactive proprotein pro-sigmaE to the mature and active form of
      the factor. Here I use immunofluorescence microscopy to show that the activation
      of the proprotein is associated with its progression through three patterns of
      subcellular localization. In the predivisional sporangium, pro-sigmaE was found
      to be associated with the cytoplasmic membrane. Next, at the stage of asymmetric
      division, pro-sigmaE accumulated at the sporulation septum. Finally, after
      processing, mature sigmaE was found to be distributed throughout the mother cell
      cytoplasm. The results of subcellular fractionation and sedimentation in density
      gradients of extracts prepared from postdivisional sporangia confirmed that pro
      sigmaE was chiefly present in the membrane fraction and that sigmaE was
      predominantly cytoplasmic, findings that suggest that the pro-amino acid sequence
      is responsible for the sequestration of pro-sigmaE to the membrane. The results
      of chemical cross-linking experiments showed that pro-sigmaE was present in a
      complex with its putative processing protein, SpoIIGA, or with a protein that
      depended on SpoIIGA. The membrane association of pro-sigmaE was, however,
      independent of SpoIIGA and other proteins specific to B. subtilis. Likewise,
      accumulation of pro-sigmaE at the septum did not depend on its interaction with
      SpoIIGA. Sequestration of pro-sigmaE to the membrane might serve to facilitate
      its interaction with SpoIIGA and may be important for preventing its premature
      association with core RNA polymerase. The implications of these findings for the
      compartmentalization of sigmaE are discussed.

PMID- 9573197
TI  - Isolation of an Escherichia coli K-12 mutant strain able to form biofilms on
      inert surfaces: involvement of a new ompR allele that increases curli expression.
AB  - Classical laboratory strains of Escherichia coli do not spontaneously colonize
      inert surfaces. However, when maintained in continuous culture for evolution
      studies or industrial processes, these strains usually generate adherent mutants
      which form a thick biofilm, visible with the naked eye, on the wall of the
      culture apparatus. Such a mutant was isolated to identify the genes and
      morphological structures involved in biofilm formation in the very well
      characterized E. coli K-12 context. This mutant acquired the ability to colonize
      hydrophilic (glass) and hydrophobic (polystyrene) surfaces and to form
      aggregation clumps. A single point mutation, resulting in the replacement of a
      leucine by an arginine residue at position 43 in the regulatory protein OmpR, was
      responsible for this phenotype. Observations by electron microscopy revealed the
      presence at the surfaces of the mutant bacteria of fibrillar structures looking
      like the particular fimbriae described by the Olsen group and designated curli
      (A. Olsen, A. Jonsson, and S. Normark, Nature 338:652-655, 1989). The production
      of curli (visualized by Congo red binding) and the expression of the csgA gene
      encoding curlin synthesis (monitored by coupling a reporter gene to its promoter)
      were significantly increased in the presence of the ompR allele described in this
      work. Transduction of knockout mutations in either csgA or ompR caused the loss
      of the adherence properties of several biofilm-forming E. coli strains, including
      all those which were isolated in this work from the wall of a continuous culture
      apparatus and two clinical strains isolated from patients with catheter-related
      infections. These results indicate that curli are morphological structures of
      major importance for inert surface colonization and biofilm formation and
      demonstrate that their synthesis is under the control of the EnvZ-OmpR two
      component regulatory system.

PMID- 9573196
TI  - The prosequence of pro-sigmaK promotes membrane association and inhibits RNA
      polymerase core binding.
AB  - Pro-sigmaK is the inactive precursor of sigmaK, a mother cell-specific sigma
      factor responsible for the transcription of late sporulation genes of Bacillus
      subtilis. Upon subcellular fractionation, the majority of the pro-sigmaK was
      present in the membrane fraction. The rest of the pro-sigmaK was in a large
      complex that did not contain RNA polymerase core subunits. In contrast, the
      majority of the sigmaK was associated with core RNA polymerase. Virtually
      identical fractionation properties were observed when pro-sigmaE was analyzed.
      Pro-sigmaK was completely solubilized from the membrane fraction and the large
      complex by Triton X-100 and was partially solubilized from the membrane fraction
      by NaCl and KSCN. The membrane association of pro-sigmaK did not require spoIVF
      gene products, which appear to be located in the mother cell membrane that
      surrounds the forespore, and govern pro-sigmaK processing in the mother cell.
      Furthermore, pro-sigmaK associated with the membrane when overproduced in
      vegetative cells. Overproduction of pro-sigmaK in sporulating cells resulted in
      more pro-sigmaK in the membrane fraction. In agreement with the results of cell
      fractionation experiments, immunofluorescence microscopy showed that pro-sigmaK
      was localized to the mother cell membranes that surround the mother cell and the
      forespore in sporulating wild-type cells and mutant cells that do not process pro
      sigmaK. Treatment of extracts with 0.6 M KCl appeared to free most of the pro
      sigmaK and sigmaK from other cell constituents. After salt removal, sigmaK, but
      not pro-sigmaK, reassociated with exogenous core RNA polymerase to form
      holoenzyme. These results suggest that the prosequence inhibits RNA polymerase
      core binding and targets pro-sigmaK to the membrane, where it may interact with
      the processing machinery.

PMID- 9573198
TI  - Gas vesicle genes identified in Bacillus megaterium and functional expression in
      Escherichia coli.
AB  - Gas vesicles are intracellular, protein-coated, and hollow organelles found in
      cyanobacteria and halophilic archaea. They are permeable to ambient gases by
      diffusion and provide buoyancy, enabling cells to move upwards in liquid to
      access oxygen and/or light. In halobacteria, gas vesicle production is encoded in
      a 9-kb cluster of 14 genes (4 of known function). In cyanobacteria, the number of
      genes involved has not been determined. We now report the cloning and sequence
      analysis of an 8,142-bp cluster of 15 putative gas vesicle genes (gvp) from
      Bacillus megaterium VT1660 and their functional expression in Escherichia coli.
      Evidence includes homologies by sequence analysis to known gas vesicle genes, the
      buoyancy phenotype of E. coli strains that carry this gvp gene cluster, the
      presence of pressure-sensitive, refractile bodies in phase-contrast microscopy,
      structural details in phase-contrast microscopy, structural details in direct
      interference-contrast microscopy, and shape and size revealed by transmission
      electron microscopy. In B. megaterium, the gvp region carries a cluster of 15
      putative genes arranged in one orientation; they are open reading frame 1 and
      gvpA, -P, -Q, -B, -R, -N, -F, -G, -L, -S, -K, -J, -T, and -U, of which the last
      11 genes, in a 5.7-kb gene cluster, are the maximum required for gas vesicle
      synthesis and function in E. coli. To our knowledge, this is the first example of
      a functional gas vesicle gene cluster in nonaquatic bacteria and the first
      example of the interspecies transfer of genes resulting in the synthesis of a
      functional organelle.

PMID- 9573199
TI  - NADH dehydrogenase defects confer isoniazid resistance and conditional lethality
      in Mycobacterium smegmatis.
AB  - Isoniazid (INH) is a highly effective drug used in the treatment and prophylaxis
      of Mycobacterium tuberculosis infections. Resistance to INH in clinical isolates
      has been correlated with mutations in the inhA, katG, and ahpC genes. In this
      report, we describe a new mechanism for INH resistance in Mycobacterium
      smegmatis. Mutations that reduce NADH dehydrogenase activity (Ndh; type II) cause
      multiple phenotypes, including (i) coresistance to INH and a related drug,
      ethionamide; (ii) thermosensitive lethality; and (iii) auxotrophy. These
      phenotypes are corrected by expression of one of two enzymes: NADH dehydrogenase
      and the NADH-dependent malate dehydrogenase of the M. tuberculosis complex. The
      genetic data presented here indicate that defects in NADH oxidation cause all of
      the mutant traits and that an increase in the NADH/NAD+ ratio confers INH
      resistance.

PMID- 9573200
TI  - Molecular cloning of the actinomycin synthetase gene cluster from Streptomyces
      chrysomallus and functional heterologous expression of the gene encoding
      actinomycin synthetase II.
AB  - The actinomycin synthetases ACMS I, II, and III catalyze the assembly of the acyl
      peptide lactone precursor of actinomycin by a nonribosomal mechanism. We have
      cloned the genes of ACMS I (acmA) and ACMS II (acmB) by hybridization screening
      of a cosmid library of Streptomyces chrysomallus DNA with synthetic
      oligonucleotides derived from peptide sequences of the two enzymes. Their genes
      were found to be closely linked and are arranged in opposite orientations.
      Hybridization mapping and partial sequence analyses indicate that the gene of an
      additional peptide synthetase, most likely the gene of ACMS III (acmC), is
      located immediately downstream of acmB in the same orientation. The protein
      sequence of ACMS II, deduced from acmB, shows that the enzyme contains two amino
      acid activation domains, which are characteristic of peptide synthetases, and an
      additional epimerization domain. Heterologous expression of acmB from the mel
      promoter of plasmid PIJ702 in Streptomyces lividans yielded a functional 280-kDa
      peptide synthetase which activates threonine and valine as enzyme-bound
      thioesters. It also catalyzes the dipeptide formation of threonyl-L-valine, which
      is epimerized to threonyl-D-valine. Both of these dipeptides are enzyme bound as
      thioesters. This catalytic activity is identical to the in vitro activity of ACMS
      II from S. chrysomallus.

PMID- 9573201
TI  - Molecular mechanism of heat shock-provoked disassembly of the coliphage lambda
      replication complex.
AB  - We have found previously that, in contrast to the free O initiator protein of
      lambda phage or plasmid rapidly degraded by the Escherichia coli ClpP/ClpX
      protease, the lambdaO present in the replication complex (RC) is protected from
      proteolysis. However, in cells growing in a complete medium, a temperature shift
      from 30 to 43 degrees C resulted in the decay of the lambdaO fraction, which
      indicated disassembly of RC. This process occurred due to heat shock induction of
      the groE operon, coding for molecular chaperones of the Hsp60 system. Here we
      demonstrate that an increase in the cellular concentration of GroEL and GroES
      proteins is not in itself sufficient to cause RC disassembly. Another requirement
      is a DNA gyrase-mediated negative resupercoiling of lambda plasmid DNA, which
      counteracts DNA relaxation and starts to dominate 10 min after the temperature
      upshift. We presume that RC dissociates from lambda DNA during the negative
      resupercoiling, becoming susceptible to the subsequent action of GroELS and
      ClpP/ClpX proteins. In contrast to lambda cro+, in lambda cro- plasmid-harboring
      cells, the RC reveals heat shock resistance. After temperature upshift of the
      lambda crots plasmid-harboring cells, a Cro repressor-independent control of
      lambda DNA replication and heat shock resistance of RC are established before the
      period of DNA gyrase-mediated negative supercoiling. We suggest that the tight
      binding of RC to lambda DNA is due to interaction of RC with other DNA-bound
      proteins, and is related to the molecular basis of the lambda cro- plasmid
      replication control.

PMID- 9573202
TI  - Mutations affecting the alpha subunit of Bordetella pertussis RNA polymerase
      suppress growth inhibition conferred by short C-terminal deletions of the
      response regulator BvgA.
AB  - The effects of short deletions of the C terminus of the BvgA response regulator
      protein of the BvgAS two-component system were examined in Bordetella pertussis.
      When present as a single copy in the chromosome, deletions removing as few as two
      amino acids conferred a completely Bvg- phenotype. When provided in trans, on the
      broad-host-range plasmid pRK290, under the control of the native bvgAS promoter,
      deletions of two or three amino acids conferred a profound growth inhibition
      which was dependent on the integrity and activity of the wild-type chromosomal
      bvgAS locus. It is proposed that this phenotype was the result of an
      inappropriate interaction of the mutant BvgA protein with the RNA polymerase
      enzyme, specifically the alpha subunit. Mutant strains in which this growth
      inhibition was relieved were isolated and characterized. Although most of the
      suppressor mutations affected either the mutant plasmid copy or the wild-type
      chromosomal bvg locus, three mutations which affected the alpha subunit of B.
      pertussis RNA polymerase were also isolated. Two of these resulted in increased
      levels of the alpha subunit, and one caused a substitution of glycine for the
      aspartic acid residue at position 171, in the N-terminal domain. All three
      mutations also resulted in a differential phenotype in that expression of fha was
      essentially normal, but expression of ptx was greatly reduced.

PMID- 9573203
TI  - Regulation of benzoate degradation in Acinetobacter sp. strain ADP1 by BenM, a
      LysR-type transcriptional activator.
AB  - In Acinetobacter sp. strain ADP1, benzoate degradation requires the ben genes for
      converting benzoate to catechol and the cat genes for degrading catechol. Here we
      describe a novel transcriptional activator, BenM, that regulates the chromosomal
      ben and cat genes. BenM is homologous to CatM, a LysR-type transcriptional
      activator of the cat genes. Unusual regulatory features of this system include
      the abilities of both BenM and CatM to recognize the same inducer, cis,cis
      muconate, and to regulate some of the same genes, such as catA and catB. Unlike
      CatM, BenM responded to benzoate. Benzoate together with cis,cis-muconate
      increased the BenM-dependent expression of the benABCDE operon synergistically.
      CatM was not required for this synergism, nor did CatM regulate the expression of
      a chromosomal benA::lacZ transcriptional fusion. BenM-mediated regulation differs
      significantly from that of the TOL plasmid-encoded conversion of benzoate to
      catechol in pseudomonads. The benM gene is immediately upstream of, and
      divergently transcribed from, benA, and a possible DNA binding site for BenM was
      identified between the two coding regions. Two mutations in the predicted
      operator/promoter region rendered ben gene expression either constitutive or
      inducible by cis,cis-muconate but not benzoate. Mutants lacking BenM, CatM, or
      both of these regulators degraded aromatic compounds at different rates, and the
      levels of intermediary metabolites that accumulated depended on the genetic
      background. These studies indicated that BenM is necessary for ben gene
      expression but not for expression of the cat genes, which can be regulated by
      CatM. In a catM-disrupted strain, BenM was able to induce higher levels of catA
      expression than catB expression.

PMID- 9573204
TI  - A novel 2-aminomuconate deaminase in the nitrobenzene degradation pathway of
      Pseudomonas pseudoalcaligenes JS45.
AB  - 2-Aminomuconate, an intermediate in the metabolism of tryptophan in mammals, is
      also an intermediate in the biodegradation of nitrobenzene by Pseudomonas
      pseudoalcaligenes JS45. Strain JS45 hydrolyzes 2-aminomuconate to 4-oxalocrotonic
      acid, with the release of ammonia, which serves as the nitrogen source for growth
      of the microorganism. As an initial step in studying the novel deamination
      mechanism, we report here the purification and some properties of 2-aminomuconate
      deaminase. The purified enzyme migrates as a single band with a molecular mass of
      16.6 kDa in 15% polyacrylamide gel electrophoresis under denaturing conditions.
      The estimated molecular mass of the native enzyme was 100 kDa by gel filtration
      and 4 to 20% gradient nondenaturing polyacrylamide gel electrophoresis,
      suggesting that the enzyme consists of six identical subunits. The enzyme was
      stable at room temperature and exhibited optimal activity at pH 6.6. The Km for 2
      aminomuconate was approximately 67 microM, and the Vmax was 125 micromol x min(
      1) x mg(-1). The N-terminal amino acid sequence of the enzyme did not show any
      significant similarity to any sequence in the databases. The purified enzyme
      converted 2-aminomuconate directly to 4-oxalocrotonate, rather than 2
      hydroxymuconate, which suggests that the deamination was carried out via an imine
      intermediate.

PMID- 9573205
TI  - Exploring the role of integral membrane proteins in ATP-binding cassette
      transporters: analysis of a collection of MalG insertion mutants.
AB  - The maltose transport complex of Escherichia coli is a well-studied example of an
      ATP-binding cassette transporter. The complex, containing one copy each of the
      integral membrane proteins MalG and MalF and two copies of the peripheral
      cytoplasmic membrane protein MalK, interacts with the periplasmic maltose-binding
      protein to efficiently translocate maltose and maltodextrins across the bacterial
      cytoplasmic membrane. To investigate the role of MalG both in MalFGK2 assembly
      interactions and in subsequent transport interactions, we isolated and
      characterized 18 different MalG mutants, each containing a 31-residue insertion
      in the protein. Eight insertions mapping to distinct hydrophilic regions of MalG
      permitted either assembly or both assembly and transport interactions to occur.
      In particular, we isolated two insertions mapping to extracytoplasmic
      (periplasmic) regions of MalG which preserved both assembly and transport
      abilities, suggesting that these are permissive sites in the protein. Another
      periplasmic insertion seems to affect only transport-specific interactions
      between MalG and maltose-binding protein, defining a novel class of MalG mutants.
      Finally, four MalG mutant proteins, although stably expressed, are unable to
      assemble into the MalFGK2 complex. These mutants contain insertions in only two
      different hydrophilic regions of MalG, consistent with the notion that a
      restricted number of domains in this protein are critical complex assembly
      determinants. These MalG mutants will allow us to further explore the
      intermolecular interactions of this model transporter.

PMID- 9573206
TI  - Developmental regulation of transcription of whiE, a locus specifying the
      polyketide spore pigment in Streptomyces coelicolor A3 (2)
AB  - whiE is a complex locus that specifies the polyketide spore pigment in
      Streptomyces coelicolor A3(2). Two divergently oriented promoters, whiEP1 and
      whiEP2, were identified in the whiE gene cluster, and their activities were
      analyzed during colony development in wild-type and sporulation-deficient
      strains. Both promoters were developmentally regulated; whiEP1 and whiEP2
      transcripts were detected transiently at approximately the time when sporulation
      septa were observed in the aerial hyphae, and transcription from both promoters
      depended on each of the six known "early" whi genes required for sporulation
      septum formation (whiA, -B, -G, -H, -I, and -J). Mutation of the late sporulation
      specific sigma factor gene, sigF, had no effect on the activity of whiEP1 but
      blocked transcription from whiEP2. However, sigmaF-containing holoenzyme was not
      sufficient to direct transcription of whiEP2 in vitro. The whiEP2 promoter
      controls expression of whiE ORFVIII, encoding a putative flavin adenine
      dinucleotide-dependent hydroxylase that catalyzes a late tailoring step in the
      spore pigment biosynthetic pathway. Disruption of whiE ORFVIII causes a change in
      spore color, from grey to greenish (T.-W. Yu and D. A. Hopwood, Microbiology
      141:2779-2791, 1995). Consistent with these observations, construction of a sigF
      null mutant of S. coelicolor M145 caused the same change in spore color, showing
      that disruption of sigF in S. coelicolor changes the nature of the spore pigment
      rather than preventing its synthesis altogether.

PMID- 9573207
TI  - A gene cluster encoding steps in conversion of naphthalene to gentisate in
      Pseudomonas sp. strain U2.
AB  - Pseudomonas sp. strain U2 was isolated from oil-contaminated soil in Venezuela by
      selective enrichment on naphthalene as the sole carbon source. The genes for
      naphthalene dioxygenase were cloned from the plasmid DNA of strain U2 on an 8.3
      kb BamHI fragment. The genes for the naphthalene dioxygenase genes nagAa (for
      ferredoxin reductase), nagAb (for ferredoxin), and nagAc and nagAd (for the large
      and small subunits of dioxygenase, respectively) were located by Southern
      hybridizations and by nucleotide sequencing. The genes for nagB (for naphthalene
      cis-dihydrodiol dehydrogenase) and nagF (for salicylaldehyde dehydrogenase) were
      inferred from subclones by their biochemical activities. Between nagAa and nagAb
      were two open reading frames, homologs of which have also been identified in
      similar locations in two nitrotoluene-using strains (J. V. Parales, A. Kumar, R.
      E. Parales, and D. T. Gibson, Gene 181:57-61, 1996; W.-C. Suen, B. Haigler, and
      J. C. Spain, J. Bacteriol. 178:4926-4934, 1996) and a naphthalene-using strain
      (G. J. Zylstra, E. Kim, and A. K. Goyal, Genet. Eng. 19:257-269, 1997).
      Recombinant Escherichia coli strains with plasmids carrying this region were able
      to convert salicylate to gentisate, which was identified by a combination of gas
      chromatography-mass spectrometry and nuclear magnetic resonance. The first open
      reading frame, designated nagG, encodes a protein with characteristics of a
      Rieske-type iron-sulfur center homologous to the large subunits of
      dihydroxylating dioxygenases, and the second open reading frame, designated nagH,
      encodes a protein with limited homology to the small subunits of the same
      dioxygenases. Cloned together in E. coli, nagG, nagH, and nagAb, were able to
      convert salicylate (2-hydroxybenzoate) into gentisate (2,5-dihydroxybenzoate) and
      therefore encode a salicylate 5-hydroxylase activity. Single-gene knockouts of
      nagG, nagH, and nagAb demonstrated their functional roles in the formation of
      gentisate. It is proposed that NagG and NagH are structural subunits of
      salicylate 5-hydroxylase linked to an electron transport chain consisting of
      NagAb and NagAa, although E. coli appears to be able to partially substitute for
      the latter. This constitutes a novel mechanism for monohydroxylation of the
      aromatic ring. Salicylate hydroxylase and catechol 2,3-dioxygenase in strain U2
      could not be detected either by enzyme assay or by Southern hybridization.
      However growth on both naphthalene and salicylate caused induction of gentisate
      1,2-dioxygenase, confirming this route for salicylate catabolism in strain U2.
      Sequence comparisons suggest that the novel gene order nagAa-nagG-nagH-nagAb
      nagAc-nagAd-++ +nagB-nagF represents the archetype for naphthalene strains which
      use the gentisate pathway rather than the meta cleavage pathway of catechol.

PMID- 9573208
TI  - Purification and biochemical characterization of the lambda holin.
AB  - Holins are small phage-encoded cytoplasmic membrane proteins, remarkable for
      their ability to make membranes permeable in a temporally regulated manner. The
      purification of S105, the lambda holin, and one of the two products of gene S is
      described. Because the wild-type S105 holin could be only partially purified from
      membrane extracts by ion-exchange chromatography, an oligohistidine tag was added
      internally to the S105 sequence for use in immobilized metal affinity
      chromatography. An acceptable site for the tag was found between residues 94 and
      95 in the highly charged C-terminal domain of S. This allele, designated S105H94,
      had normal lysis timing under physiological expression conditions. The S105H94
      protein was overproduced, purified, and characterized by circular dichroism
      spectroscopy, which revealed approximately 40% alpha-helix conformation,
      consistent with the presence of two transmembrane helices. The purified protein
      was then used to achieve release of fluorescent dye loaded in liposomes in vitro,
      whereas protein from an isogenic construct carrying an S mutation known to
      abolish hole formation was inactive in this assay. These results suggest that S
      is a bitopic membrane protein capable of forming aqueous holes in bilayers.

PMID- 9573209
TI  - A seven-gene locus for synthesis of phenazine-1-carboxylic acid by Pseudomonas
      fluorescens 2-79.
AB  - Pseudomonas fluorescens 2-79 produces the broad-spectrum antibiotic phenazine-1
      carboxylic acid (PCA), which is active against a variety of fungal root
      pathogens. In this study, seven genes designated phzABCDEFG that are sufficient
      for synthesis of PCA were localized within a 6.8-kb BglII-XbaI fragment from the
      phenazine biosynthesis locus of strain 2-79. Polypeptides corresponding to all
      phz genes were identified by analysis of recombinant plasmids in a T7
      promoter/polymerase expression system. Products of the phzC, phzD, and phzE genes
      have similarities to enzymes of shikimic acid and chorismic acid metabolism and,
      together with PhzF, are absolutely necessary for PCA production. PhzG is similar
      to pyridoxamine-5'-phosphate oxidases and probably is a source of cofactor for
      the PCA-synthesizing enzyme(s). Products of the phzA and phzB genes are highly
      homologous to each other and may be involved in stabilization of a putative PCA
      synthesizing multienzyme complex. Two new genes, phzX and phzY, that are
      homologous to phzA and phzB, respectively, were cloned and sequenced from P.
      aureofaciens 30-84, which produces PCA, 2-hydroxyphenazine-1-carboxylic acid, and
      2-hydroxyphenazine. Based on functional analysis of the phz genes from strains 2
      79 and 30-84, we postulate that different species of fluorescent pseudomonads
      have similar genetic systems that confer the ability to synthesize PCA.

PMID- 9573211
TI  - The Saccharomyces cerevisiae YCC5 (YCL025c) gene encodes an amino acid permease,
      Agp1, which transports asparagine and glutamine.
AB  - The yeast YCC5 gene encodes a putative amino acid permease and is homologous to
      GNP1 (encoding a high-affinity glutamine permease). Using strains with
      disruptions in the genes for multiple permeases, we demonstrated that Ycc5 (which
      we have renamed Agp1) is involved in the transport of asparagine and glutamine,
      performed a kinetic analysis of this activity, and showed that AGP1 expression is
      subject to nitrogen repression.

PMID- 9573210
TI  - Regulation of a new cell wall hydrolase gene, cwlF, which affects cell separation
      in Bacillus subtilis.
AB  - Bacillus subtilis produces a 35-kDa cell wall hydrolase, CwlF, during vegetative
      growth. The CwlF protein was extracted from B. subtilis cwlB sigD mutant cells
      and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N
      terminal amino acid sequencing revealed that its sequence is completely identical
      to that of the internal region of the papQ gene product. Disruption of the papQ
      gene in the B. subtilis chromosome led to the complete loss of CwlF, indicating
      that papQ is identical to cwlF. CwlF exhibits high sequence similarity to the p60
      proteins of Listeria species, NlpC proteins of Escherichia coli and Haemophilus
      influenzae, and Enp2 protein of Bacillus sphaericus. The beta-galactosidase
      activity of the cwlF-lacZ transcriptional fusion and Northern blot analysis of
      the cwlF gene indicated that the gene is expressed as a monocistronic operon
      during the exponential growth phase, and primer extension analysis suggested that
      the cwlF gene is transcribed mainly by EsigmaA RNA polymerase and weakly by
      EsigmaH RNA polymerase. While the cells of the cwlF-deficient mutant were about
      twice as long as those of the wild-type strain, the cwlF sigD double mutant cells
      exhibited extraordinary microfiber formation, in contrast to the filamentation of
      the sigD mutant. The CwlF production was not affected by the pleiotropic
      mutations flaD1 and degU32(Hy), which endow cells with the ability of extensive
      filamentation.

PMID- 9573212
TI  - Small abundant DNA binding proteins from the thermoacidophilic archaeon
      Sulfolobus shibatae constrain negative DNA supercoils.
AB  - Major DNA binding proteins, designated Ssh7, were purified from the
      thermoacidophilic archaeon Sulfolobus shibatae. The Ssh7 proteins have an
      apparent molecular mass of 6.5 kDa and are similar to the 7-kDa DNA binding
      proteins from Sulfolobus acidocaldarius and Sulfolobus solfataricus in N-terminal
      amino acid sequence. The proteins constitute about 4.8% of the cellular protein.
      Upon binding to DNA, the Ssh7 proteins constrain negative supercoils. At the
      tested Ssh7/DNA mass ratios (0 to 1.65), one negative supercoil was taken up by
      approximately 20 Ssh7 molecules. Our results, together with the observation that
      the viral DNA isolated from S. shibatae is relaxed, suggest that regions of free
      DNA in the S. shibatae genome, if present, are highly positively supercoiled.

PMID- 9573213
TI  - Division planes alternate in spherical cells of Escherichia coli.
AB  - In the spherical cells of Escherichia coli rodA mutants, division is initiated at
      a single point, from which a furrow extends progressively around the cell. Using
      "giant" rodA ftsA cells, we confirmed that each new division furrow is initiated
      at the midpoint of the previous division plane and runs perpendicular to it.

PMID- 9573214
TI  - Identification and analysis of "extended -10" promoters from mycobacteria.
AB  - Earlier studies from our laboratory on randomly isolated transcriptional signals
      of mycobacteria had revealed that the -10 region of mycobacterial promoters and
      the corresponding binding domain in the major sigma factor are highly similar to
      their Escherichia coli counterparts. In contrast, the sequences in -35 regions of
      mycobacterial promoters and the corresponding binding domain in the major sigma
      factor are vastly different from their E. coli counterparts (M. D. Bashyam, D.
      Kaushal, S. K. Dasgupta, and A. K. Tyagi, J. Bacteriol. 178:4847-4853, 1996). We
      have now analyzed the role of the TGN motif present immediately upstream of the 
      10 region of mycobacterial promoters. Sequence analysis and site-specific
      mutagenesis of a Mycobacterium tuberculosis promoter and a Mycobacterium
      smegmatis promoter reveal that the TGN motif is an important determinant of
      transcriptional strength in mycobacteria. We show that mutation in the TGN motif
      can drastically reduce the transcriptional strength of a mycobacterial promoter.
      The influence of the TGN motif on transcriptional strength is also modulated by
      the sequences in the -35 region. Comparative assessment of these extended -10
      promoters in mycobacteria and E. coli suggests that functioning of the TGN motif
      in promoters of these two species is similar.

PMID- 9573215
TI  - Identification and enzymatic characterization of the maltose-inducible alpha
      glucosidase MalL (sucrase-isomaltase-maltase) of Bacillus subtilis.
AB  - A gene coding for a putative alpha-glucosidase has been identified in the open
      reading frame yvdL (now termed malL), which was sequenced as part of the Bacillus
      subtilis genome project. The enzyme was overproduced in Escherichia coli and
      purified. Further analyses indicate that MalL is a specific oligo-1,4-1,6-alpha
      glucosidase (sucrase-maltase-isomaltase). MalL expression in B. subtilis requires
      maltose induction and is subject to carbon catabolite repression by glucose and
      fructose. Insertional mutagenesis of malL resulted in a complete inactivation of
      the maltose-inducible alpha-glucosidase activity in crude protein extracts and a
      Mal- phenotype.

PMID- 9573216
TI  - Coordinated repression in vitro of the divergent fepA-fes promoters of
      Escherichia coli by the iron uptake regulation (Fur) protein.
AB  - The mechanism involved in transcriptional repression of the fepA-fes divergent
      promoters of Escherichia coli by the Fur (ferric uptake regulation) protein has
      been examined in vitro. This DNA region includes a suboptimal and single Fur
      binding site with two divergent and overlapped -35/-10 hexamers. Comparison of
      transcription patterns generated with runoff experiments in either the presence
      or the absence of heparin showed that access of the RNA polymerase to the
      principal -35/-10 hexamers was fully prevented by Fur-Mn2+ bound to its target
      site within the divergent promoter region. Neither RNA polymerase bound to the
      fes and fepA promoters could be displaced by Fur-Mn2+, nor could the bound
      repressor be outcompeted by an excess of the enzyme. However, the repressor
      blocked reinitiation as soon as the polymerase moved away from the fes promoter
      during transcription. The spatial distribution of regulatory elements within the
      DNA region allowed the simultaneous binding of the RNA polymerase to the fes and
      fepA promoters and their coordinate regulation regardless of their different
      transcriptional activities. Comparisons with other iron-regulated systems support
      a general mechanism for Fur-controlled promoters that implies a direct
      competition between the polymerase and the regulator for overlapping target sites
      in the DNA.

PMID- 9573217
TI  - Does nitric oxide play a critical role in viral infections?

PMID- 9573218
TI  - Characterization of determinants for envelope binding and infection in tva, the
      subgroup A avian sarcoma and leukosis virus receptor.
AB  - Tva is the cellular receptor for subgroup A avian leukosis and sarcoma virus
      (ALSV-A). The viral interaction domain of Tva is determined by a 40-residue,
      cysteine-rich module closely related to the ligand binding domain of the human
      low-density lipoprotein receptor (LDLR). In this report, we examined the role of
      the LDLR-like module of Tva in envelope binding and viral infection by mutational
      analysis. We found that the entire LDLR module in Tva is essential for efficient
      binding to the viral envelope protein. However, the 17 N-terminal residues of
      this module can be deleted without affecting receptor function, suggesting that
      the major determinants for viral entry are located at the C terminus of the
      module. The effect on viral infection of many amino acid substitutions and
      deletions in the LDLR module is context dependent, suggesting that the residues
      important for viral entry are dispersed throughout the LDLR module. In addition,
      we found that all 27 mutations at residues D46, E47, and W48 greatly reduced
      envelope binding. These results are discussed in relation to a recently
      elucidated structure for an LDLR module.

PMID- 9573219
TI  - The Us9 gene product of pseudorabies virus, an alphaherpesvirus, is a
      phosphorylated, tail-anchored type II membrane protein.
AB  - The Us9 gene is highly conserved among the alphaherpesviruses sequenced to date,
      yet its function remains unknown. In this report, we demonstrate that the
      pseudorabies virus (PRV) Us9 protein is present in infected cell lysates as
      several phosphorylated polypeptides ranging from 17 to 20 kDa. Synthesis is first
      detected at 6 h postinfection and is sensitive to the DNA synthesis inhibitor
      phosphonoacetic acid. Unlike the herpes simplex virus type 1 Us9 homolog, which
      was reported to be associated with nucleocapsids in the nuclei of infected cells
      (M. C. Frame, D. J. McGeoch, F. J. Rixon, A. C. Orr, and H. S. Marsden, Virology
      150:321-332, 1986), PRV Us9 localizes to the secretory pathway (predominately to
      the Golgi apparatus) and not to the nucleus. By fusing the enhanced green
      fluorescent protein (EGFP) reporter molecule to the carboxy terminus of Us9, we
      demonstrated that Us9 not only is capable of targeting a Us9-EGFP fusion protein
      to the Golgi compartment but also is able to direct efficient incorporation of
      such chimeric molecules into infectious viral particles. Moreover, through
      protease digestion experiments with Us9-EGFP-containing viral particles, we
      demonstrated that the Us9 protein is inserted into the viral envelope as a type
      II, tail-anchored membrane protein.

PMID- 9573220
TI  - Role of envelope protein gE endocytosis in the pseudorabies virus life cycle.
AB  - Several groups have reported that certain herpesvirus envelope proteins do not
      remain on the surface of cells that express them but rather are internalized by
      endocytosis in a recycling process. The biological function of membrane protein
      endocytosis in the virus life cycle remains a matter of speculation and debate.
      In this report, we demonstrate that some, but not all, membrane proteins encoded
      by the alphaherpesvirus pseudorabies virus (PRV) are internalized after reaching
      the plasma membrane. Glycoproteins gE and gB are internalized from the plasma
      membrane of cells, while gI and gC are not internalized efficiently. We show for
      gE that the cytoplasmic domain of the protein is required for endocytosis. While
      the gI protein is incapable of endocytosis on its own, it can be internalized
      when complexed with gE. We demonstrate that endocytosis of the gE-gI complex and
      gB occurs early after infection of tissue culture cells but that this process
      stops completely after 6 h of infection, a time that correlates with significant
      shutoff of host protein synthesis. We also show that gE protein internalized at 4
      h postinfection is not present in virions formed at a later time. We discuss the
      differences in PRV gE and gI endocytosis compared to that of the varicella-zoster
      virus homologs and the possible roles of glycoprotein endocytosis in the virus
      life cycle.

PMID- 9573221
TI  - A chicken embryo eye model for the analysis of alphaherpesvirus neuronal spread
      and virulence.
AB  - We describe use of developing chicken embryos as a model to study neuronal spread
      and virulence of pseudorabies virus (PRV). At embryonic day 12, beta
      galactosidase-expressing PRV strains were injected into the vitreous humor of one
      eye, and virus replication and spread from the eye to the brain were measured by
      beta-galactosidase activity and the recovery of infectious virus from tissues.
      The wild-type PRV strain, Becker, replicated in the eye and then spread to the
      brain, causing extensive pathology characterized by edema, hemorrhage, and
      necrosis that localized to virally infected tissue. The attenuated vaccine
      strain, Bartha, replicated in the eye and spread throughout specific regions of
      the brain, producing little to no overt pathology. Becker mutants lacking
      membrane proteins gE or gI replicated in the eye and were able to spread to the
      brain efficiently. The pathology associated with replication of these mutants in
      the brain was intermediate to that induced by Becker or Bartha. Mixed infection
      of a gE deletion mutant and a gI deletion mutant restored the pathogenic
      phenotype to wild-type levels. These data indicate that the replication of virus
      in embryonic brain tissue is not sufficient to induce the characteristic
      pathological response and that the gE and gI gene products actively affect
      pathological responses in the developing chicken brain.

PMID- 9573222
TI  - Ligand induction of retinoic acid receptors alters an acute infection by murine
      cytomegalovirus.
AB  - Here we report that administration of retinoids can alter the outcome of an acute
      murine cytomegalovirus (MCMV) infection. We show that a crucial viral control
      element, the major immediate-early enhancer, can be activated by retinoic acid
      (RA) via multiple RA-responsive elements (DR2) that bind retinoid X receptor
      retinoic acid receptor (RAR) heterodimers with apparent dissociation constants
      ranging from 15 to 33 nM. Viral growth is dramatically increased upon RA
      treatment of infected tissue culture cells. Using synthetic retinoid receptor
      specific agonists and antagonists, we provide evidence that RAR activation in
      cells is required for mediating the response of MCMV to RA. Oral administration
      of RA to infected immunocompetent mice selectively exacerbates an infection by
      MCMV, while cotreatment with an RAR antagonist protects against the adverse
      effects of RA on MCMV infection. In conclusion, these chemical genetic
      experiments provide evidence that an RAR-mediated pathway can modulate in vitro
      and in vivo infections by MCMV.

PMID- 9573223
TI  - Combinatorial blockade of calcineurin and CD28 signaling facilitates primary and
      secondary therapeutic gene transfer by adenovirus vectors in dystrophic (mdx)
      mouse muscles.
AB  - Recombinant adenovirus vectors (AdV) have been considered a potential vehicle for
      performing gene therapy in patients suffering from Duchenne muscular dystrophy
      but are limited by a cellular and humoral immune response that prevents long-term
      transgene expression as well as effective transduction after AdV
      readministration. Conventional immunosuppressive agents such as cyclosporine and
      FK506, which act by interfering with CD3-T-cell receptor-mediated signaling via
      calcineurin, are only partially effective in reversing these phenomena and may
      also produce substantial organ toxicity. We hypothesized that activation of
      redundant T-cell activation pathways could limit the effectiveness of these drugs
      at clinically tolerable doses. Therefore, we have tested the ability of
      immunomodulatory immunoglobulins (Ig) with different modes of action to
      facilitate AdV-mediated gene transfer to adult dystrophic (mdx) mice. When used
      in isolation, immunomodulatory Ig (anti-intercellular adhesion molecule-1, anti
      leukocyte function-associated antigen-1, anti-CD2, and CTLA4Ig) were only mildly
      effective in mitigating cellular and/or humoral immunity against adenovirus
      capsid proteins and the therapeutic transgene product, dystrophin. However, the
      combination of FK506 plus CTLA4Ig abrogated the immune response against
      adenovirus proteins and dystrophin to a degree not achievable with the use of
      either agent alone. At 30 days after AdV injection, >90% of myofibers could be
      found to express dystrophin with little or no evidence of a cellular immune
      response against transduced fibers. In addition, the humoral immune response was
      markedly suppressed, and this was associated with increased transduction
      efficiency following vector readministration. These data suggest that by
      facilitating both primary and secondary transduction after AdV administration,
      combined targeting of CD3-T-cell receptor-mediated signaling via calcineurin and
      the B7:CD28 costimulatory pathway could greatly increase the potential utility of
      AdV-mediated gene transfer as a therapeutic modality for genetic diseases such as
      Duchenne muscular dystrophy that will require long-term transgene expression and
      repeated vector delivery.

PMID- 9573224
TI  - Antibody-mediated neutralization of human rhinovirus 14 explored by means of
      cryoelectron microscopy and X-ray crystallography of virus-Fab complexes.
AB  - The structures of three different human rhinovirus 14 (HRV14)-Fab complexes have
      been explored with X-ray crystallography and cryoelectron microscopy procedures.
      All three antibodies bind to the NIm-IA site of HRV14, which is the beta-B-beta-C
      loop of the viral capsid protein VP1. Two antibodies, Fab17-IA (Fab17) and Fab12
      IA (Fab12), bind bivalently to the virion surface and strongly neutralize viral
      infectivity whereas Fab1-IA (Fab1) strongly aggregates and weakly neutralizes
      virions. The structures of the two classes of virion-Fab complexes clearly differ
      and correlate with observed binding neutralization differences. Fab17 and Fab12
      bind in essentially identical, tangential orientations to the viral surface,
      which favors bidentate binding over icosahedral twofold axes. Fab1 binds in a
      more radial orientation that makes bidentate binding unlikely. Although the
      binding orientations of these two antibody groups differ, nearly identical charge
      interactions occur at all paratope-epitope interfaces. Nucleotide sequence
      comparisons suggest that Fab17 and Fab12 are from the same progenitor cell and
      that some of the differing residues contact the south wall of the receptor
      binding canyon that encircles each of the icosahedral fivefold vertices. All of
      the antibodies contact a significant proportion of the canyon region and directly
      overlap much of the receptor (intercellular adhesion molecule 1 [ICAM-1]) binding
      site. Fab1, however, does not contact the same residues on the upper south wall
      (the side facing away from fivefold axes) at the receptor binding region as do
      Fab12 and Fab17. All three antibodies cause some stabilization of HRV14 against
      pH-induced inactivation; thus, stabilization may be mediated by invariant
      contacts with the canyon.

PMID- 9573225
TI  - Loss of CD4+ T cells in human immunodeficiency virus type 1-infected chimpanzees
      is associated with increased lymphocyte apoptosis.
AB  - Supportive evidence that apoptosis contributes to loss of CD4+ lymphocytes in
      human immunodeficiency virus type 1 (HIV-1)-infected humans comes from an
      apparent lack of abnormal apoptosis in apathogenic lentivirus infections of
      nonhuman primates, including HIV-1 infection of chimpanzees. Two female
      chimpanzees were inoculated, one cervically and the other intravenously, with HIV
      1 derived from the LAI/LAV-1b strain, which was isolated from a chimpanzee
      infected with the virus for 8 years. Within 6 weeks of infection, both recipient
      chimpanzees developed a progressive loss of CD4+ T cells which correlated with
      persistently high viral burdens and increased levels of CD4+ T-cell apoptosis
      both in vitro and in vivo. Lymph nodes from both animals also revealed evidence
      of immune hyperactivation. Intermediate levels of T-cell apoptosis in both
      peripheral blood and lymph nodes were seen in a third chimpanzee that had been
      infected with the LAI/LAV-1b strain for 9 years; this animal has maintained
      depressed CD4/CD8 T-cell ratios for the last 3 years. Similar analyses of cells
      from 4 uninfected animals and 10 other HIV-1-infected chimpanzees without loss of
      CD4+ cells revealed no difference in levels of apoptosis in these two control
      groups. These results demonstrate a correlation between immune hyperactivation, T
      cell apoptosis, and chronic loss of CD4+ T cells in HIV-1-infected chimpanzees,
      providing additional evidence that apoptosis is an important factor in T-cell
      loss in AIDS. Furthermore, the results show that some HIV-1 strains are
      pathogenic for chimpanzees and that this species is not inherently resistant to
      HIV-1-induced disease.

PMID- 9573226
TI  - Human immunodeficiency virus type 1 T-lymphotropic strains enter macrophages via
      a CD4- and CXCR4-mediated pathway: replication is restricted at a postentry
      level.
AB  - The human immunodeficiency virus type 1 (HIV-1) laboratory strains adapted to T
      cell lines, as well as most syncytium-inducing primary isolates, replicate poorly
      in macrophages, which, beside CD4(+) T lymphocytes, are major targets of HIV-1.
      In the present work, we used a semiquantitative PCR-based technique to study
      viral entry into cells, kinetics of reverse transcription, and translocation of
      the viral DNA into the nucleus of macrophages infected with different HIV-1
      strains. Our results demonstrate that T-lymphotropic strains efficiently enter
      macrophages. Entry was inhibited by a monoclonal antibody against CD4 and by
      stromal cell-derived factor 1alpha, a natural ligand of CXCR4, suggesting that
      both CD4 and CXCR4 act as receptors on macrophages for HIV-1 T-lymphotropic
      strains. Analysis of the kinetics of reverse transcription and nuclear import
      revealed that the most pronounced differences between T-lymphotropic and
      macrophagetropic strains occurred at the level of nuclear translocation of viral
      DNA, although a delay in reverse transcription was also observed. These results
      suggest that postentry steps are critical for restricted replication of T
      lymphotropic HIV-1 strains in macrophages.

PMID- 9573227
TI  - Infection of glial cells by the human polyomavirus JC is mediated by an N-linked
      glycoprotein containing terminal alpha(2-6)-linked sialic acids.
AB  - The human JC polyomavirus (JCV) is the etiologic agent of the fatal central
      nervous system (CNS) demyelinating disease progressive multifocal
      leukoencephalopathy (PML). PML typically occurs in immunosuppressed patients and
      is the direct result of JCV infection of oligodendrocytes. The initial event in
      infection of cells by JCV is attachment of the virus to receptors present on the
      surface of a susceptible cell. Our laboratory has been studying this critical
      event in the life cycle of JCV, and we have found that JCV binds to a limited
      number of cell surface receptors on human glial cells that are not shared by the
      related polyomavirus simian virus 40 (C. K. Liu, A. P. Hope, and W. J. Atwood, J.
      Neurovirol. 4:49-58, 1998). To further characterize specific JCV receptors on
      human glial cells, we tested specific neuraminidases, proteases, and
      phospholipases for the ability to inhibit JCV binding to and infection of glial
      cells. Several of the enzymes tested were capable of inhibiting virus binding to
      cells, but only neuraminidase was capable of inhibiting infection. The ability of
      neuraminidase to inhibit infection correlated with its ability to remove both
      alpha(2-3)- and alpha(2-6)-linked sialic acids from glial cells. A recombinant
      neuraminidase that specifically removes the alpha(2-3) linkage of sialic acid had
      no effect on virus binding or infection. A competition assay between virus and
      sialic acid-specific lectins that recognize either the alpha(2-3) or the alpha(2
      6) linkage revealed that JCV preferentially interacts with alpha(2-6)-linked
      sialic acids on glial cells. Treatment of glial cells with tunicamycin, but not
      with benzyl N-acetyl-alpha-D-galactosaminide, inhibited infection by JCV,
      indicating that the sialylated JCV receptor is an N-linked glycoprotein. As
      sialic acid containing glycoproteins play a fundamental role in mediating many
      virus-cell and cell-cell recognition processes, it will be of interest to
      determine what role these receptors play in the pathogenesis of PML.

PMID- 9573228
TI  - Evaluation of the Galalpha1-3Gal epitope as a host modification factor eliciting
      natural humoral immunity to enveloped viruses.
AB  - Human sera contain high levels of natural antibody (Ab) to Galalpha1-3Gal, a
      terminal glycosidic structure expressed on the surface of cells of mammals other
      than Old World primates. Incorporation of this determinant onto retroviral
      membranes by passage of viruses in cells encoding alpha-1-3-galactosyltransferase
      (GT) renders retroviruses sensitive to lysis by natural Ab and complement in
      normal human serum (NHS). Plasma membrane-budding viruses representing four
      additional virus groups were examined for their sensitivities to serum
      inactivation after passage through human cell lines that lack a functional GT or
      human cells expressing recombinant porcine GT. The inactivation of lymphocytic
      choriomeningitis virus (LCMV) by NHS directly correlated with host modification
      of the virus via expression of Galalpha1-3Gal and was blocked by incorporation of
      soluble Galalpha1-3Gal disaccharide into the inactivation assay. GT-deficient
      mice immunized to make high levels of Ab to Galalpha1-3Gal (anti-Gal Ab) were
      tested for resistance to LCMV passaged in GT-expressing cells. Resistance was not
      observed, but in vitro analyses of the mouse immune sera revealed that the
      antiviral activity of the sera was insufficient to eliminate LCMV infectivity on
      its natural targets of infection, macrophages, which express receptors for Ab and
      complement. Newcastle disease virus and vesicular stomatitis virus (VSV) were
      inactivated by NHS regardless of cell passage history, whereas Sindbis virus (SV)
      passaged in human cells resisted inactivation. Both VSV and SV passaged in
      Galalpha1-3Gal-expressing human cells incorporated this sugar moiety onto their
      major envelope glycoproteins. SV passaged in mouse cells expressing Galalpha1
      3Gal was moderately sensitive to inactivation by NHS. These results indicate that
      enveloped viruses expressing Galalpha1-3Gal differ in their sensitivities to NHS
      and that a potent complement source, such as that in NHS, is required for
      efficient inactivation of sensitive viruses in vitro and in vivo.

PMID- 9573229
TI  - Rep*: a viral element that can partially replace the origin of plasmid DNA
      synthesis of Epstein-Barr virus.
AB  - Replication of the Epstein-Barr viral (EBV) genome occurs once per cell cycle
      during latent infection. Similarly, plasmids containing EBV's plasmid origin of
      replication, oriP, are replicated once per cell cycle. Replication from oriP
      requires EBV nuclear antigen 1 (EBNA-1) in trans; however, its contributions to
      this replication are unknown. oriP contains 24 EBNA-1 binding sites; 20 are
      located within the family of repeats, and 4 are found within the dyad symmetry
      element. The site of initiation of DNA replication within oriP is at or near the
      dyad symmetry element. We have identified a plasmid that contains the family of
      repeats but lacks the dyad symmetry element whose replication can be detected for
      a limited number of cell cycles. The detection of short-term replication of this
      plasmid requires EBNA-1 and can be inhibited by a dominant-negative inhibitor of
      EBNA-1. We have identified two regions within this plasmid which can
      independently contribute to this replication in the absence of the dyad symmetry
      element of oriP. One region contains native EBV sequences within the BamHI C
      fragment of the B95-8 genome of EBV; the other contains sequences within the
      simian virus 40 genome. We have mapped the region contributing to replication
      within the EBV sequences to a 298-bp fragment, Rep*. Plasmids which contain three
      copies of Rep* plus the family of repeats support replication more efficiently
      than those with one copy, consistent with a stochastic model for the initiation
      of DNA synthesis. Plasmids with three copies of Rep* also support long-term
      replication in the presence of EBNA-1. These observations together indicate that
      the latent origin of replication of EBV is more complex than formerly
      appreciated; it is a multicomponent origin of which the dyad symmetry element is
      one efficient component. The experimental approach described here could be used
      to identify eukaryotic sequences which mediate DNA synthesis, albeit
      inefficiently.

PMID- 9573230
TI  - Particle size determinants in the human immunodeficiency virus type 1 Gag
      protein.
AB  - The retroviral Gag protein plays the central role in the assembly process and can
      form membrane-enclosed, virus-like particles in the absence of any other viral
      products. These particles are similar to authentic virions in density and size.
      Three small domains of the human immunodeficiency virus type 1 (HIV-1) Gag
      protein have been previously identified as being important for budding. Regions
      that lie outside these domains can be deleted without any effect on particle
      release or density. However, the regions of Gag that control the size of HIV-1
      particles are less well understood. In the case of Rous sarcoma virus (RSV), the
      size determinant maps to the CA (capsid) and adjacent spacer sequences within
      Gag, but systematic mapping of the HIV Gag protein has not been reported. To
      locate the size determinants of HIV-1, we analyzed a large collection of Gag
      mutants. To our surprise, all mutants with defects in the MA (matrix), CA, and
      the N-terminal part of NC (nucleocapsid) sequences produced dense particles of
      normal size, suggesting that oncoviruses (RSV) and lentiviruses (HIV-1) have
      different size-controlling elements. The most important region found to be
      critical for determining HIV-1 particle size is the p6 sequence. Particles
      lacking all or small parts of p6 were uniform in size distribution but very large
      as measured by rate zonal gradients. Further evidence for this novel function of
      p6 was obtained by placing this sequence at the C terminus of RSV CA mutants that
      produce heterogeneously sized particles. We found that the RSV-p6 chimeras
      produced normally sized particles. Thus, we present evidence that the entire p6
      sequence plays a role in determining the size of a retroviral particle.

PMID- 9573231
TI  - Mutations in the human immunodeficiency virus type 1 integrase D,D(35)E motif do
      not eliminate provirus formation.
AB  - The core domain of human immunodeficiency virus type 1 (HIV-1) integrase (IN)
      contains a D,D(35)E motif, named for the phylogenetically conserved glutamic acid
      and aspartic acid residues and the invariant 35 amino acid spacing between the
      second and third acidic residues. Each acidic residue of the D,D(35)E motif is
      independently essential for the 3'-processing and strand transfer activities of
      purified HIV-1 IN protein. Using a replication-defective viral genome with a
      hygromycin selectable marker, we recently reported that a mutation at any of the
      three residues of the D,D(35)E motif produces a 10(3)- to 10(4)-fold reduction in
      infectious titer compared with virus encoding wild-type IN (A. D. Leavitt et al.,
      J. Virol. 70:721-728. 1996). The infectious titer, as measured by the number of
      hygromycin-resistant colonies formed following infection of cells in culture, was
      less than a few hundred colonies per microg of p24. To understand the mechanism
      by which the mutant virions conferred hygromycin resistance, we characterized the
      integrated viral DNA in cells infected with virus encoding mutations at each of
      the three residues of the D,D(35)E motif. We found the integrated viral DNA to be
      colinear with the incoming viral genome. DNA sequencing of the junctions between
      integrated viral DNA and host DNA showed that (i) the characteristic 5-bp direct
      repeat of host DNA flanking the HIV-1 provirus was not maintained, (ii)
      integration often produced a deletion of host DNA, (iii) integration sometimes
      occurred without the viral DNA first undergoing 3'-processing, (iv) integration
      sites showed a strong bias for a G residue immediately adjacent to the conserved
      viral CA dinucleotide, and (v) mutations at each of the residues of the D,D(35)E
      motif produced essentially identical phenotypes. We conclude that mutations at
      any of the three acidic residues of the conserved D,D(35)E motif so severely
      impair IN activity that most, if not all, integration events by virus encoding
      such mutations are not IN mediated. IN-independent provirus formation may have
      implications for anti-IN therapeutic agents that target the IN active site.

PMID- 9573232
TI  - Vpr stimulates viral expression and induces cell killing in human
      immunodeficiency virus type 1-infected dividing Jurkat T cells.
AB  - In this study we investigated the effects of Vpr during human immunodeficiency
      virus (HIV) infection of proliferating Jurkat T cells by using a vesicular
      stomatitis virus envelope G glycoprotein pseudotyped HIV superinfection system.
      We observe that the expression of Vpr results in a severe reduction in the life
      span of HIV type 1 (HIV-1)-infected dividing T cells in culture. In agreement
      with a recent report (S. A. Stewart, B. Poon, J. B. M. Jowett, and I. S. Chen, J.
      Virol. 71:5579-5592, 1997), we show that events characteristic of apoptotic cell
      death are involved in the Vpr-mediated cytopathic effects. Our results also show
      that infection with viruses expressing the wild-type vpr gene results in an
      increase in viral gene expression and production. Interestingly, the effects of
      Vpr on cell viability and on viral gene expression both correlate with the
      ability of the protein to induce a cell cycle arrest in the G2/M phase.
      Mutagenesis analyses show that the C terminus of Vpr is essential for these
      biological activities. Although the role of Vpr is currently associated with the
      infection of nondividing cells, our results suggest that Vpr can also directly
      increase viral replication in vivo in infected dividing T cells. Furthermore,
      these in vitro observations suggest that Vpr-mediated cytotoxic effects could
      contribute to the CD4+ depletion associated with AIDS progression.

PMID- 9573234
TI  - Vaccination with a recombinant vesicular stomatitis virus expressing an influenza
      virus hemagglutinin provides complete protection from influenza virus challenge.
AB  - Since the development of a system for generating vesicular stomatitis virus (VSV)
      from plasmid DNAs, our laboratory has reported the expression of several
      different glycoproteins from recombinant VSVs. In one of these studies, high
      level expression of an influenza virus hemagglutinin (HA) from a recombinant VSV
      HA and efficient incorporation of the HA protein into the virions was reported
      (E. Kretzschmar, L. Buonocore, M. J. Schnell, and J. K. Rose, J. Virol. 71:5982
      5989, 1997). We report here that VSV-HA is an effective intranasal vaccine vector
      that raises high levels of neutralizing antibody to influenza virus and
      completely protects mice from bronchial pneumonia caused by challenge with a
      lethal dose of influenza A virus. Additionally, these recombinant VSVs are less
      pathogenic than wild-type VSV (serotype Indiana). This vector-associated
      pathogenicity was subsequently eliminated through introduction of specific
      attenuating deletions. These live attenuated recombinant VSVs have great
      potential as vaccine vectors.

PMID- 9573233
TI  - CD4-Induced conformational changes in the human immunodeficiency virus type 1
      gp120 glycoprotein: consequences for virus entry and neutralization.
AB  - Human immunodeficiency virus type 1 (HIV-1) entry into target cells involves
      sequential binding of the gp120 exterior envelope glycoprotein to CD4 and to
      specific chemokine receptors. Soluble CD4 (sCD4) is thought to mimic membrane
      anchored CD4, and its binding alters the conformation of the HIV-1 envelope
      glycoproteins. Two cross-competing monoclonal antibodies, 17b and CG10, that
      recognize CD4-inducible gp120 epitopes and that block gp120-chemokine receptor
      binding were used to investigate the nature and functional significance of gp120
      conformational changes initiated by CD4 binding. Envelope glycoproteins derived
      from both T-cell line-adapted and primary HIV-1 isolates exhibited increased
      binding of the 17b antibody in the presence of sCD4. CD4-induced exposure of the
      17b epitope on the oligomeric envelope glycoprotein complex occurred over a wide
      range of temperatures and involved movement of the gp120 V1/V2 variable loops.
      Amino acid changes that reduced the efficiency of 17b epitope exposure following
      CD4 binding invariably compromised the ability of the HIV-1 envelope
      glycoproteins to form syncytia or to support virus entry. Comparison of the CD4
      dependence and neutralization efficiencies of the 17b and CG10 antibodies
      suggested that the epitopes for these antibodies are minimally accessible
      following attachment of gp120 to cell surface CD4. These results underscore the
      functional importance of these CD4-induced changes in gp120 conformation and
      illustrate viral strategies for sequestering chemokine receptor-binding regions
      from the humoral immune response.

PMID- 9573235
TI  - Inhibition of phosphodiesterase type IV suppresses human immunodeficiency virus
      type 1 replication and cytokine production in primary T cells: involvement of NF
      kappaB and NFAT.
AB  - Rolipram, a phosphosdiesterase type IV-specific inhibitor, prevented p24 antigen
      release from anti-CD3-activated human immunodeficiency virus (HIV)-infected T
      cells and CD4(+)-cell depletion associated with viral replication in a dose
      responsive manner but minimally inhibited T-cell proliferation. Moreover,
      rolipram reduced the production of tumor necrosis factor alpha (TNF-alpha) and
      interleukin-10 (IL-10) by HIV-infected T cells. The transcriptional ability of a
      luciferase reporter gene under control of the HIV long terminal repeat, induced
      by phorbol myristic acetate plus ionomycin or by TNF-alpha, in primary T and
      Jurkat cells was also inhibited by rolipram. Rolipram inhibited NF-kappaB and
      NFAT activation induced by T-cell activation in Jurkat and primary T cells, as
      measured by transient transfection of reporter genes and electrophoretic mobility
      shift assays. Exogenous addition of TNF-alpha in the presence of rolipram
      restored NF-kappaB but not NFAT activation or p24 release. Addition of dibutyryl
      cyclic AMP (dBcAMP) mimicked the effects of rolipram on p24 antigen release, NF
      kappaB activation, and TNF-alpha secretion, but it did not affect NFAT activation
      or IL-10 production. The protein kinase A inhibitor KT5720 prevented the
      inhibition of TNF-alpha secretion but not that of HIV type 1 (HIV-1) replication
      caused by rolipram. Our data indicate that blockade of phosphodiesterase type IV
      could be of benefit against HIV-1 disease by modulating cytokine secretion and
      transcriptional regulation of HIV replication, and they suggest an important role
      of NFAT in HIV replication in primary T cells. Some of those activities cannot be
      ascribed solely to its ability to increase cAMP.

PMID- 9573236
TI  - Resistance of human cytomegalovirus to benzimidazole ribonucleosides maps to two
      open reading frames: UL89 and UL56.
AB  - 2,5,6-Trichloro-1-beta-D-ribofuranosyl benzimidazole (TCRB) is a potent and
      selective inhibitor of human cytomegalovirus (HCMV) replication. TCRB acts via a
      novel mechanism involving inhibition of viral DNA processing and packaging.
      Resistance to the 2-bromo analog (BDCRB) has been mapped to the UL89 open reading
      frame (ORF), and this gene product was proposed as the viral target of the
      benzimidazole nucleosides. In this study, we report the independent isolation of
      virus that is 20- to 30-fold resistant to TCRB (isolate C4) and the
      characterization of the virus. The six ORFs known to be essential for viral DNA
      cleavage and packaging (UL51, UL52, UL56, UL77, UL89, and UL104) were sequenced
      from wild-type HCMV, strain Towne, and from isolate C4. Mutations were identified
      in UL89 (D344E) and in UL56 (Q204R). The mutation in UL89 was identical to that
      previously reported for virus resistant to BDCRB, but the mutation in UL56 is
      novel. Marker transfer analysis demonstrated that each of these mutations
      individually caused approximately 10-fold resistance to the benzimidazoles and
      that the combination of both mutations caused approximately 30-fold resistance.
      The rate and extent of replication of the mutants was the same as for wild-type
      virus, but the viruses were less sensitive to inhibition of DNA cleavage by TCRB.
      Mapping of resistance to UL56 supports and extends recent work showing that UL56
      codes for a packaging motif binding protein which also has specific nuclease
      activity (E. Bogner et al., J. Virol. 72:2259-2264, 1998). Resistance which maps
      to two different genes suggests that their putative proteins interact and/or that
      either or both have a benzimidazole ribonucleoside binding site. The results also
      suggest that the gene products of UL89 and UL56 may be antiviral drug targets.

PMID- 9573237
TI  - The nucleoside triphosphatase and helicase activities of vaccinia virus NPH-II
      are essential for virus replication.
AB  - Vaccinia virus NPH-II is the prototypal RNA helicase of the DExH box protein
      family, which is defined by six shared sequence motifs. The contributions of
      conserved amino acids in motifs I (TGVGKTSQ), Ia (PRI), II (DExHE), and III (TAT)
      to enzyme activity were assessed by alanine scanning. NPH-II-Ala proteins were
      expressed in baculovirus-infected Sf9 cells, purified, and characterized with
      respect to their RNA helicase, nucleic acid-dependent ATPase, and RNA binding
      functions. Alanine substitutions at Lys-191 and Thr-192 (motif I), Arg-229 (motif
      Ia), and Glu-300 (motif II) caused severe defects in RNA unwinding that
      correlated with reduced rates of ATP hydrolysis. In contrast, alanine mutations
      at His-299 (motif II) and at Thr-326 and Thr-328 (motif III) elicited defects in
      RNA unwinding but spared the ATPase. None of the mutations analyzed affected the
      binding of NPH-II to RNA. These findings, together with previous mutational
      studies, indicate that NPH-II motifs I, Ia, II, and VI (QRxGRxGRxxxG) are
      essential for nucleoside triphosphate (NTP) hydrolysis, whereas motif III and the
      His moiety of the DExH-box serve to couple the NTPase and helicase activities.
      Wild-type and mutant NPH-II-Ala genes were tested for the ability to rescue
      temperature-sensitive nph2-ts viruses. NPH-II mutations that inactivated the
      phosphohydrolase in vitro were lethal in vivo, as judged by the failure to
      recover rescued viruses containing the Ala substitution. The NTPase activity was
      necessary, but not sufficient, to sustain virus replication, insofar as mutants
      for which NTPase was uncoupled from unwinding (H299A, T326A, and T328A) were also
      lethal. We conclude that the phosphohydrolase and helicase activities of NPH-II
      are essential for virus replication.

PMID- 9573238
TI  - Infectious bovine viral diarrhea virus (strain NADL) RNA from stable cDNA clones:
      a cellular insert determines NS3 production and viral cytopathogenicity.
AB  - Bovine viral diarrhea virus (BVDV), strain NADL, was originally isolated from an
      animal with fatal mucosal disease. This isolate is cytopathic in cell culture and
      produces two forms of NS3-containing proteins: uncleaved NS2-3 and mature NS3.
      For BVDV NADL, the production of NS3, a characteristic of cytopathic BVDV
      strains, is believed to be a consequence of an in-frame insertion of a 270
      nucleotide cellular mRNA sequence (called cIns) in the NS2 coding region. In this
      study, we constructed a stable full-length cDNA copy of BVDV NADL in a low-copy
      number plasmid vector. As assayed by transfection of MDBK cells, uncapped RNAs
      transcribed from this template were highly infectious (>10(5) PFU/microg). The
      recovered virus was similar in plaque morphology, growth properties, polyprotein
      processing, and cytopathogenicity to the BVDV NADL parent. Deletion of cIns
      abolished processing at the NS2/NS3 site and produced a virus that was no longer
      cytopathic for MDBK cells. This deletion did not affect the efficiency of
      infectious virus production or viral protein production, but it reduced the level
      of virus-specific RNA synthesis and accumulation. Thus, cIns not only modulates
      NS3 production but also upregulates RNA replication relative to an isogenic
      noncytopathic derivative lacking the insert. These results raise the possibility
      of a linkage between enhanced BVDV NADL RNA replication and virus-induced
      cytopathogenicity.

PMID- 9573239
TI  - Mutational and functional analysis of the C-terminal region of the C3H mouse
      mammary tumor virus superantigen.
AB  - The mouse mammary tumor virus (MMTV) encodes within the U3 region of the long
      terminal repeat (LTR) a protein known as the superantigen (Sag). Sag is needed
      for the efficient transmission of milk-borne virus from the gut to target tissue
      in the mammary gland. MMTV-infected B cells in the gut express Sag as a type II
      transmembrane protein that is recognized by the variable region of particular
      beta chains (Vbeta) of the T-cell receptor (TCR) on the surface of T cells.
      Recognition of Sag by particular TCRs results in T-cell stimulation, release of
      cytokines, and amplification of MMTV infection in lymphoid cells that are needed
      for infection of adolescent mammary tissue. Because the C-terminal 30 to 40 amino
      acids of Sag are variable and correlate with recognition of particular TCR Vbeta
      chains, we prepared a series of C-terminal Sag mutations that were introduced
      into a cloned infectious MMTV provirus. Virus-producing XC rat cells were used
      for injection of susceptible BALB/c mice, and these mice were monitored for
      functional Sag activity by the deletion of C3H MMTV Sag-reactive (CD4+ Vbeta14+)
      T cells. Injected mice also were analyzed for mutant infection and tumor
      formation in mammary glands as well as milk-borne transmission of MMTV to
      offspring. Most mutations abrogated Sag function, although one mutation (HPA242)
      that changed the negative charge of the extreme C terminus to a positive charge
      created a weaker Sag that slowed the kinetics of Sag-mediated T-cell deletion.
      Despite the lack of Sag activity, many of the sag mutant viruses were capable of
      sporadic infections of the mammary glands of injected mice but not of offspring
      mice, indicating that functional Sag increases the probability of milk-borne MMTV
      infection. Furthermore, although most viruses encoding nonfunctional Sags were
      unable to cause mammary tumors, tumors were induced by such viruses carrying
      mutations in a negative regulatory element that overlaps the sag gene within the
      LTR, suggesting that loss of Sag function may be compensated, at least partially,
      by loss of transcriptional suppression in certain tissues. Together these results
      confirm the importance of Sag for efficient milk-borne transmission and indicate
      that the entire C-terminal region is needed for complete Sag function.

PMID- 9573240
TI  - Cell-specific expression of RANTES, MCP-1, and MIP-1alpha by lower airway
      epithelial cells and eosinophils infected with respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in
      infancy, a syndrome characterized by wheezing, respiratory distress, and the
      pathologic findings of peribronchial mononuclear cell infiltration and release of
      inflammatory mediators by basophil and eosinophil leukocytes. Composition and
      activation of this cellular response are thought to rely on the discrete target
      cell selectivity of C-C chemokines. We demonstrate that infection in vitro of
      human epithelial cells of the lower respiratory tract by RSV induced dose- and
      time-dependent increases in mRNA and protein secretion for RANTES (regulated upon
      activation, normal T-cell expressed and presumably secreted), monocyte
      chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP
      1alpha). Production of MCP-1 and MIP-1alpha was selectively localized only in
      epithelial cells of the small airways and lung. Exposure of epithelial cells to
      gamma interferon (IFN-gamma), in combination with RSV infection, induced a
      significant increase in RANTES production that was synergistic with respect to
      that obtained by RSV infection or IFN-gamma treatment alone. Epithelial cell
      derived chemokines exhibited a strong chemotactic activity for normal human blood
      eosinophils. Furthermore, eosinophils were susceptible to RSV and released RANTES
      and MIP-1alpha as a result of infection. Therefore, the inflammatory process in
      RSV-induced bronchiolitis appears to be triggered by the infection of epithelial
      cells and further amplified via mechanisms driven by IFN-gamma and by the
      secretion of eosinophil chemokines.

PMID- 9573242
TI  - Specific interaction of eukaryotic translation initiation factor 3 with the 5'
      nontranslated regions of hepatitis C virus and classical swine fever virus RNAs.
AB  - Translation of hepatitis C virus (HCV) and classical swine fever virus (CSFV)
      RNAs is initiated by cap-independent attachment (internal entry) of ribosomes to
      the approximately 350-nucleotide internal ribosomal entry segment (IRES) at the
      5' end of both RNAs. Eukaryotic initiation factor 3 (eIF3) binds specifically to
      HCV and CSFV IRESs and plays an essential role in the initiation process on them.
      Here we report the results of chemical and enzymatic footprinting analyses of
      binary eIF3-IRES complexes, which have been used to identify the eIF3 binding
      sites on HCV and CSFV IRESs. eIF3 protected an internal bulge in the apical stem
      IIIb of domain III of the CSFV IRES from chemical modification and protected
      bonds in and adjacent to this bulge from cleavage by RNases ONE and V1. eIF3
      protected an analagous region in domain III of the HCV IRES from cleavage by
      these enzymes. These results are consistent with the results of primer extension
      analyses and were supported by observations that deletion of stem-loop IIIb or of
      the adjacent hairpin IIIc from the HCV IRES abrogated the binding of eIF3 to this
      RNA. This is the first report that eIF3 is able to bind a eukaryotic mRNA in a
      sequence- or structure-specific manner. UV cross-linking of eIF3 to [32P]UTP
      labelled HCV and CSFV IRES elements resulted in strong labelling of 4 (p170,
      p116, p66, and p47) of the 10 subunits of eIF3, 1 or more of which are likely to
      be determinants of these interactions. In the cytoplasm, eIF3 is
      stoichiometrically associated with free 40S ribosomal subunits. The results
      presented here are consistent with a model in which binding of these two
      translation components to separate, specific sites on both HCV and CSFV IRESs
      enhances the efficiency and accuracy of binding of these RNAs to 40S subunits in
      an orientation that promotes entry of the initiation codon into the ribosomal P
      site.

PMID- 9573241
TI  - Mutations in the leucine zipper-like heptad repeat sequence of human
      immunodeficiency virus type 1 gp41 dominantly interfere with wild-type virus
      infectivity.
AB  - It has been previously shown that a proline substitution for any of the conserved
      leucine or isoleucine residues located in the leucine zipper-like heptad repeat
      sequence of human immunodeficiency virus type 1 (HIV-1) gp41 renders viruses
      noninfectious and envelope (Env) protein unable to mediate membrane fusion (S. S.
      L. Chen, C.-N. Lee, W.-R. Lee, K. McIntosh, and T.-M. Lee, J. Virol. 67:3615
      3619, 1993; S. S.-L. Chen, J. Virol. 68:2002-2010, 1994). To understand whether
      these variants could act as trans-dominant inhibitory mutants, the ability of
      these mutants to inhibit wild-type (wt) virus infectivity was examined.
      Comparable amounts of cell- and virion-associated gag gene products as well as
      virion-associated gp41 were found in transfection with wt or mutant HIV-1
      provirus. Viruses obtained from coexpression of wt provirus with mutant 566 or
      580 provirus inhibited more potently the production of infectious virus than did
      viruses generated from cotransfection of wt provirus with other mutant
      proviruses. Nevertheless, all viruses produced from mixed transfection showed
      decreased infectivity compared with that of the wt virus when a multinuclear
      activation beta-galactosidase induction assay was performed. The ability of wt
      Env to induce cytopathic effects was inhibited by coexpression with mutant Env.
      Coexpression of mutants inhibited the ability of the wt protein to mediate virus
      to-cell transmission, as demonstrated by an env trans-complementation assay with
      a defective HIV-1 proviral vector. These observations indicated that mutant Env,
      per se, interferes with wt Env function. Moreover, cotransfection of wt and
      mutant proviruses produced amounts of cell- and virion-associated gag gene
      products comparable to those produced by transfection of wt provirus. Similar
      amounts of gp41 were also found in virions generated from wt-mutant
      cotransfection as well as from wt transfection alone. These results indicated
      that the inhibitory effect conferred by mutants on the wt virus infectivity does
      not involve the late steps of Gag protein assembly and budding, but they suggest
      that the wt and mutant Env proteins form a dysfunctional hetero-oligomer which is
      impaired in an early step of the virus replication cycle. Our study demonstrates
      that mutations in the HIV-1 gp41 leucine zipper-like heptad repeat sequence
      dominantly inhibit infectious virus production.

PMID- 9573243
TI  - Initiation of hepatitis delta virus genome replication.
AB  - The small, 195-amino-acid form of the hepatitis delta virus (HDV) antigen
      (deltaAg-S) is essential for genome replication, i.e., for the transcription,
      processing, and accumulation of HDV RNAs. To better understand this requirement,
      we used purified recombinant deltaAg-S and HDV RNA synthesized in vitro to
      assemble high-molecular-weight ribonucleoprotein (RNP) structures. After
      transfection of these RNPs into human cells, we detected HDV genome replication,
      as assayed by Northern analysis or immunofluorescence microscopy. Our
      interpretation is that the input deltaAg-S is necessary for the RNA to undergo
      limited amounts of RNA-directed RNA synthesis, RNA processing, and mRNA
      formation, leading to de novo translation of deltaAg-S. It is this second source
      of deltaAg-S which then goes on to support genome replication. This assay made it
      possible to manipulate in vitro the composition of the RNP and then test in vivo
      the ability of the complex to initiate RNA-directed RNA synthesis and go on to
      achieve genome replication. For example, both genomic and antigenomic linear RNAs
      were acceptable. Substitution for deltaAg-S with truncated or modified forms of
      the deltaAg, and even with HIV nucleocapsid protein and polylysine, was
      unacceptable; the exception was a form of deltaAg-S with six histidines added at
      the C terminus. We expect that further in vitro modifications of these RNP
      complexes should help define the in vivo requirements for what we define as the
      initiation of HDV genome replication.

PMID- 9573244
TI  - The p95 gene of Bombyx mori nuclear polyhedrosis virus: temporal expression and
      functional properties.
AB  - As part of our effort to identify baculovirus proteins acting as transcriptional
      regulators, we have characterized a gene, p95, of Bombyx mori nuclear
      polyhedrosis virus (BmNPV) that encompasses an open reading frame for a putative
      95-kDa polypeptide (P95). The N-terminal half of the conceptually translated P95
      contains two zinc finger-type DNA-binding motifs, and its C terminus contains a
      proline-rich region reminiscent of transcriptional activation regions. Northern
      blot analysis indicates that two mRNA species, 3.5 and 1.7 kb in size, are
      transcribed from the p95 gene at different times postinfection. These two mRNA
      species are produced by differential polyadenylation site usage. While the longer
      transcript can encode the P95 protein, the shorter one may encode a prematurely
      terminated version of the P95 polypeptide produced by ribosome frameshifting
      occurring at heptanucleotide "slippage" sites located near the relevant
      polyadenylation site. Transcription of the p95 gene is initiated at a proximal
      site located 70 nucleotides upstream of the translation start codon of P95, a
      middle site located 170 nucleotides from the start codon, and a set of three
      closely spaced distal sites located 385, 390, and 409 nucleotides from the
      translation start codon. The middle and distant initiation sites are utilized
      before and after BmNPV DNA replication, while transcripts initiated at the
      proximal site occur largely during the late and very late stages of viral
      infection. Transient-expression assays indicate that P95 can stimulate gene
      expression driven by the promoter of its own gene and the promoter of the
      cytoplasmic actin gene of B. mori. The P95-mediated trans activation can be
      further augmented by BmIE1, an immediate-early gene product of BmNPV. In contrast
      to the case with the actin promoter, however, the promoter of the p95 gene can be
      trans activated by the product of its own gene only in the presence of BmIE1. Our
      data suggest that proteins P95 and BmIE1 of BmNPV and, by analogy, those of other
      baculoviruses may interact with each other and synergize to potentiate
      transcription.

PMID- 9573245
TI  - N-Terminal extension of human immunodeficiency virus capsid protein converts the
      in vitro assembly phenotype from tubular to spherical particles.
AB  - Expression of retroviral Gag polyproteins is sufficient for morphogenesis of
      virus-like particles with a spherical immature protein shell. Proteolytic
      cleavage of Gag into the matrix (MA), capsid (CA), nucleocapsid (NC), and p6
      domains (in the case of human immunodeficiency virus [HIV]) leads to condensation
      to the mature cone-shaped core. We have analyzed the formation of spherical or
      cylindrical particles on in vitro assembly of purified HIV proteins or inside
      Escherichia coli cells. CA protein alone yielded cylindrical particles, while all
      N-terminal extensions of CA abolished cylinder formation. Spherical particles
      with heterogeneous diameters or amorphous protein aggregates were observed
      instead. Extending CA by 5 amino acids was sufficient to convert the assembly
      phenotype to spherical particles. Sequences C-terminal of CA were not required
      for sphere formation. Proteolytic cleavage of N-terminally extended CA proteins
      prior to in vitro assembly led to the formation of cylindrical particles, while
      proteolysis of in vitro assembly products caused disruption of spheres but not
      formation of cylinders. In vitro assembly of CA and extended CA proteins in the
      presence of cyclophilin A (CypA) at a CA-to-CypA molar ratio of 10:1 yielded
      significantly longer cylinders and heterogeneous spheres, while higher
      concentrations of CypA completely disrupted particle formation. We conclude that
      the spherical shape of immature HIV particles is determined by the presence of an
      N-terminal extension on the CA domain and that core condensation during virion
      maturation requires the liberation of the N terminus of CA.

PMID- 9573246
TI  - Rescue and autonomous replication of adeno-associated virus type 2 genomes
      containing Rep-binding site mutations in the viral p5 promoter.
AB  - The Rep proteins encoded by the adeno-associated virus type 2 (AAV) play a
      crucial role in the rescue, replication, and integration of the viral genome. In
      the absence of a helper virus, little expression of the AAV Rep proteins occurs,
      and the AAV genome fails to undergo DNA replication. Since previous studies have
      established that expression of the Rep78 and Rep68 proteins from the viral p5
      promoter is controlled by the Rep-binding site (RBS) and the YY1 factor-binding
      site (YBS), we constructed a number of recombinant AAV plasmids containing
      mutations and/or deletions of the RBS and the YBS in the p5 promoter. These
      plasmids were transfected in HeLa or 293 cells and analyzed for the potential to
      undergo AAV DNA rescue and replication. Our studies revealed that (i) a low-level
      rescue and autonomous replication of the wild-type AAV genome occurred in 293 but
      not in HeLa cells; (ii) mutations in the RBS resulted in augmented expression
      from the p5 promoter, leading to more efficient rescue and/or replication of the
      AAV genome in 293 but not in HeLa cells; (iii) little rescue and/or replication
      occurred from plasmids containing mutations in the YBS alone in the absence of
      coinfection with adenovirus; (iv) expression of the adenovirus E1A gene products
      was insufficient to mediate rescue and/or replication of the AAV genome in HeLa
      cells; (v) autonomously replicated AAV genomes in 293 cells were successfully
      encapsidated in mature progeny virions that were biologically active in secondary
      infection of HeLa cells in the presence of adenovirus; and (vi) stable
      transfection of recombinant AAV plasmids containing a gene for resistance to
      neomycin significantly affected stable integration only in 293 cells, presumably
      because rescue and autonomous replication of the AAV genome from these plasmids
      occurred in 293 cells but not in HeLa or KB cells. These data suggest that in the
      absence of adenovirus, the AAV Rep protein-RBS interaction plays a dominant role
      in down-regulating viral gene expression from the p5 promoter and that
      perturbation in this interaction is sufficient to confer autonomous replication
      competence to AAV in 293 cells.

PMID- 9573247
TI  - Importance of ribosomal frameshifting for human immunodeficiency virus type 1
      particle assembly and replication.
AB  - The recent development and use of protease inhibitors have demonstrated the
      essential role that combination therapy will play in the treatment of individuals
      infected with the human immunodeficiency virus type 1 (HIV-1). Past clinical
      experience suggests that due to the appearance of resistant HIV-1 variants,
      additional therapeutics will be required in the future. To identify new options
      for combination therapy, it is of paramount importance to pursue novel targets
      for drug development. Ribosomal frameshifting is one potential target that has
      not been fully explored. Data presented here demonstrate that small molecules can
      stimulate frameshifting, leading to an imbalance in the ratio of Gag to Gag-Pol
      and inhibiting HIV-1 replication at what appears to be the point of viral
      particle assembly. Thus, we propose that frameshifting represents a new target
      for the identification of novel anti-HIV-1 therapeutics.

PMID- 9573248
TI  - Role of interleukin-12 in primary influenza virus infection.
AB  - The effect of endogenous interleukin-12 (IL-12) on the influenza virus immune
      response in BALB/c mice was evaluated. Following primary influenza virus
      infection, IL-12 mRNA and protein are detected in the lung, with live virus being
      required for cytokine induction. Endogenous IL-12 contributes to early NK cell
      dependent gamma interferon (IFN-gamma) production (days 3 and 5) but not late T
      cell-dependent IFN-gamma secretion (day 7). IL-12 contributes to the inhibition
      of early virus replication but is not required for virus clearance. IL-12 also
      modestly contributes to the activation of cytotoxic T lymphocytes. Thus, in this
      model of experimental influenza virus infection, endogenous IL-12 contributes
      primarily to the early development and activation of the innate immune response.

PMID- 9573249
TI  - Cationic liposomes enhance the rate of transduction by a recombinant retroviral
      vector in vitro and in vivo.
AB  - Cationic liposomes enhanced the rate of transduction of target cells with
      retroviral vectors. The greatest effect was seen with the formulation DC
      Chol/DOPE, which gave a 20-fold increase in initial transduction rate. This
      allowed an efficiency of transduction after brief exposure of target cells to
      virus plus liposome that could be achieved only after extensive exposure to virus
      alone. Enhancement with DC-Chol/DOPE was optimal when stable virion-liposome
      complexes were preformed. The transduction rate for complexed virus, as for virus
      used alone or with the polycation Polybrene, showed first-order dependence on
      virus concentration. Cationic liposomes, but not Polybrene, were able to mediate
      envelope-independent transduction, but optimal efficiency required envelope
      receptor interaction. When virus complexed with DC-Chol/DOPE was used to
      transduce human mesothelioma xenografts, transduction was enhanced four- to
      fivefold compared to that for virus alone. Since the efficacy of gene therapy is
      dependent on the number of cells modified, which is in turn dependent upon the
      balance between transduction and biological clearance of the vector, the ability
      of cationic liposomes to form stable complexes with retroviral vectors and
      enhance their rate of infection is likely to be important for in vivo
      application.

PMID- 9573250
TI  - Structure-based mutational analysis of the C-terminal DNA-binding domain of human
      immunodeficiency virus type 1 integrase: critical residues for protein
      oligomerization and DNA binding.
AB  - The C-terminal domain of human immunodeficiency virus type 1 (HIV-1) integrase
      (IN) is a dimer that binds to DNA in a nonspecific manner. The structure of the
      minimal region required for DNA binding (IN220-270) has been solved by nuclear
      magnetic resonance spectroscopy. The overall fold of the C-terminal domain of HIV
      1 IN is similar to those of Src homology region 3 domains. Based on the structure
      of IN220-270, we studied the role of 15 amino acid residues potentially involved
      in DNA binding and oligomerization by mutational analysis. We found that two
      amino acid residues, arginine 262 and leucine 234, contribute to DNA binding in
      the context of IN220-270, as indicated by protein-DNA UV cross-link analysis. We
      also analyzed mutant proteins representing portions of the full-length IN
      protein. Amino acid substitution of residues located in the hydrophobic dimer
      interface, such as L241A and L242A, results in the loss of oligomerization of IN;
      consequently, the levels of 3' processing, DNA strand transfer, and
      intramolecular disintegration are strongly reduced. These results suggest that
      dimerization of the C-terminal domain of IN is important for correct
      multimerization of IN.

PMID- 9573251
TI  - The major component of IkappaBalpha proteolysis occurs independently of the
      proteasome pathway in respiratory syncytial virus-infected pulmonary epithelial
      cells.
AB  - Previously we showed that infection of human type II airway epithelial (A549)
      cells with purified respiratory syncytial virus (pRSV) induced interleukin-8
      transcription by a mechanism involving cytokine-inducible cytoplasmic-nuclear
      translocation of the RelA transcription factor. In unstimulated cells, RelA is
      tethered in the cytoplasm by association with the IkappaB inhibitor and can be
      released only following IkappaB degradation. In this study, we examined the
      spectrum of IkappaB isoform expression and kinetics of proteolysis of the
      isoforms in A549 cells following pRSV infection. In contrast to the rapid and
      robust activation of RelA DNA binding that peaked within 15 min of treatment
      produced by the prototypic activator tumor necrosis factor alpha (TNF-alpha),
      pRSV produced a weaker increase in RelA binding that began at 3 h and did not
      peak until 24 h after infection. A549 cells expressed the IkappaB inhibitory
      subunits IkappaBalpha, IkappaBbeta, and p105; however, following either stimulus,
      only the IkappaBalpha and IkappaBbeta steady-state levels declined in parallel
      with the increase in RelA DNA-binding activity. The >120-min half-life of
      IkappaBalpha in control cells was shortened to 5 min in TNF-alpha-stimulated
      cells and to 90 min in pRSV-infected cells. Although IkappaBalpha was
      resynthesized within 30 min following recombinant human TNFalpha treatment due to
      a robust 25-fold increase of IkappaBalpha mRNA expression (the RelA:IkappaBalpha
      positive feedback loop), following pRSV infection, there was no reaccumulation of
      IkappaBalpha protein, as infected cells produced only a 3-fold increase in
      IkappaBalpha mRNA at 24 h, indicating the RelA:IkappaBalpha positive feedback
      loop was insufficient to restore control IkappaBalpha levels. IkappaBalpha
      proteolysis induced by TNF-alpha occurred through the 26S proteasome, as both 26S
      proteasome activity and IkappaBalpha proteolysis were blocked by specific
      inhibitors lactacystin, MG-132, and ZLLF-CHO. Although total proteasome activity
      in 24-h pRSV-infected lysates increased twofold, its activity was >90% inhibited
      by the proteasome inhibitors; surprisingly, however, IkappaBalpha proteolysis was
      not. We conclude that RSV infection produces IkappaBalpha proteolysis through a
      mechanism primarily independent of the proteasome pathway.

PMID- 9573252
TI  - 3'-Azido-3'-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs
      in the case of AZT-resistant human immunodeficiency virus type 1 variants.
AB  - Difficulties in deciphering the mechanisms of 3'-azido-3'-deoxythymidine (AZT)
      resistance by human immunodeficiency virus type 1 (HIV-1) variants are due in
      part to an inability to reconstitute resistance in vitro using AZT-resistant
      reverse transcriptases. We decided to characterize mechanisms of AZT resistance
      in tissue culture infections by studying the ability of drug-resistant viruses to
      synthesize viral DNA in the presence or absence of drug. Through use of PCR
      amplifications, we discovered an AZT-mediated stimulation of reverse
      transcription by AZT-resistant viruses carrying the M41L and T215Y mutations that
      can apparently override the inhibitory effects of AZT-5'-triphosphate. In
      addition, the presence of AZT also causes viruses containing the M41L and T215Y
      substitutions to have diminished sensitivity to other nucleoside analogs (i.e.,
      ddC, ddI, and d4T). This AZT-mediated cross-resistance may help to explain the
      virological failure of treatment regimens that included ddI plus AZT or ddC plus
      AZT in situations in which the T215Y and/or M41L mutations were present (F. Brun
      Vezinet, C. Boucher, C. Loveday, D. Descamps, V. Fauveau, J. Izopet, D. Jeffries,
      S. Kaye, C. Krzyanowski, A. Nunn, R. Schuurman, J. M. Seigneurin, C. Tamalet, R.
      Tedder, J. Weber, and G. J. Weverling, Lancet 350:983-990, 1997). Our results
      suggest that the use of AZT may be contraindicated in those patients for whom
      resistance to this compound (M41L and/or T215Y) has been demonstrated.

PMID- 9573253
TI  - Vaccine-induced, pseudorabies virus-specific, extrathymic CD4+CD8+ memory T
      helper cells in swine.
AB  - Pseudorabies virus (PRV; suid herpesvirus 1) infection causes heavy economic
      losses in the pig industry. Therefore, vaccination with live attenuated viruses
      is practiced in many countries. This vaccination was demonstrated to induce
      extrathymic virus-specific memory CD4+CD8+ T lymphocytes. Due to their major
      histocompatibility complex (MHC) class II-restricted proliferation, it is
      generally believed that these T lymphocytes function as memory T-helper cells. To
      directly prove this hypothesis, 15-amino-acid, overlapping peptides of the viral
      glycoprotein gC were used for screening in proliferation assays with peripheral
      blood mononuclear cells of vaccinated d/d haplotype inbred pigs. In these
      experiments, two naturally processed T-cell epitopes (T1 and T2) which are MHC
      class II restricted were identified. It was shown that extrathymic CD4+CD8+ T
      cells are the T-lymphocyte subpopulation that responds to epitope T2. In
      addition, we were able to show that cytokine secretion can be induced in these T
      cells through recall with inactivated PRV and demonstrated that activated PRV
      primed CD4+CD8+ T cells are able to induce PRV-specific immunoglobulin synthesis
      by PRV-primed, resting B cells. Taken together, these results demonstrate that
      the glycoprotein gC takes part in the priming of humoral anti-PRV memory
      responses. The experiments identified the first T-cell epitopes so far known to
      induce the generation of virus-specific CD4+CD8+ memory T lymphocytes and showed
      that CD4+CD8+ T cells are memory T-helper cells. Therefore, this study describes
      the generation of virus-specific CD4+CD8+ T cells, which is observed during
      vaccination, as a part of the potent humoral anti-PRV memory response induced by
      the vaccine.

PMID- 9573254
TI  - The Rep52 gene product of adeno-associated virus is a DNA helicase with 3'-to-5'
      polarity.
AB  - The rep gene of adeno-associated virus type 2 encodes four overlapping proteins
      from two separate promoters, termed P5 and P19. The P5-promoted Rep proteins,
      Rep78 and Rep68, are essential for viral DNA replication, and a wealth of data
      concerning the biochemical activities of these proteins has been reported. In
      contrast, data concerning the biochemical functions of the P19-promoted Rep
      proteins, Rep52 and Rep40, are lacking. Here, we describe enzymatic activities
      associated with a bacterially expressed maltose-binding protein (MBP)-Rep52
      fusion protein. Purified MBP-Rep52 possesses 3'-to-5' DNA helicase activity that
      is strictly dependent upon the presence of nucleoside triphosphate and divalent
      cation cofactors. In addition, MBP-Rep52 demonstrates a constitutive ATPase
      activity that is active in the absence of DNA effector molecules. An MBP-Rep52
      chimera bearing a lysine-to-histidine substitution at position 116 (K116H) within
      a consensus helicase- and ATPase-associated motif (motif I or Walker A site) was
      deficient for both DNA helicase and ATPase activities. In contrast to a Rep78 A
      site mutant protein bearing a corresponding amino acid substitution at position
      340 (K340H), the MBP-Rep52 A-site mutant protein failed to exhibit a trans
      dominant negative effect when it was mixed with wild-type MBP-Rep52 or MBP-Rep78
      in vitro. This lack of trans dominance, coupled with the results of
      coimmunoprecipitation and gel filtration chromatography experiments reported
      here, suggests that the ability of Rep52 to engage in multimeric interactions may
      differ from that of Rep78 or -68.

PMID- 9573255
TI  - High-efficiency gene transfer into normal and adenosine deaminase-deficient T
      lymphocytes is mediated by transduction on recombinant fibronectin fragments.
AB  - Primary human T lymphocytes are powerful targets for genetic modification,
      although the use of these targets in human gene therapy protocols has been
      hampered by low levels of transduction. We have shown previously that significant
      increases in the transduction of hematopoietic stem and progenitor cells with
      retroviral vectors can be obtained by the colocalization of the retrovirus and
      target cells on specific fibronectin (FN) adhesion domains (H. Hanenberg, X. L.
      Xiao, D. Dilloo, K. Hashino, I. Kato, and D. A. Williams, Nat. Med. 2:876-882,
      1996). We studied the transfer of genes into primary T lymphocytes by using FN
      assisted retroviral gene transfer. Activated T lymphocytes were infected for
      three consecutive days on the recombinant FN fragment CH-296 with a retroviral
      vector encoding the murine B7-1 protein. Transduced lymphocytes were analyzed for
      murine B7-1 expression, and it was found that under optimal conditions, 80 to 89%
      of the CD3+ lymphocytes were transduced. Gene transfer was predominantly
      augmented by the interaction between VLA-4 on the T lymphocytes and the FN
      adhesion site CS-1. Adenosine deaminase (ADA)-deficient primary T lymphocytes
      transduced on CH-296 with a retrovirus encoding murine ADA (mADA) exhibited
      levels of mADA activity severalfold higher than the levels of the endogenous
      human ADA protein observed in normal human T lymphocytes. Strikingly, the long
      term expression of the transgene was dependent on the activation status of the
      lymphocytes. This approach will have important applications in human gene therapy
      protocols targeting primary T lymphocytes.

PMID- 9573257
TI  - An evolutionarily conserved splice generates a secreted env-Bet fusion protein
      during human foamy virus infection.
AB  - Foamy viruses (spumaretroviruses) represent a retroviral genus which exhibits
      unusual features relating it to pararetroviruses. Previously, we reported the
      existence of a protein species harboring Env, Bel, and Bet epitopes in human
      foamy virus (HFV)-infected cells (M. L. Giron, F. Rozain, M. C. Debons-Guillemin,
      M. Canivet, J. Peries, and R. Emanoil-Ravier, J. Virol. 67:3596-3600, 1993).
      Here, we identify this protein as a 160-kDa Env-Bet fusion glycoprotein (gp160)
      translated from an mRNA species harboring a highly conserved splice site which
      deletes the membrane anchor domain of Env and fuses the env open reading frame
      with that of bel1/bet. While gp160 and Bet proteins were both secreted into the
      supernatant, only Bet was taken up by recipient cells. Since Bet plays a key role
      in the switch from lytic to chronic infection, secretion of Bet and gp160,
      together with cellular uptake of Bet, could be highly relevant for both immune
      response and development of HFV infection in vivo.

PMID- 9573256
TI  - Long-term evolution of the hypervariable region of hepatitis C virus in a common
      source-infected cohort.
AB  - The long-term evolution of the hepatitis C virus hypervariable region (HVR) and
      flanking regions of the E1 and E2 envelope proteins have been studied in a cohort
      of women infected from a common source of anti-D immunoglobulin. Whereas virus
      sequences in the infectious source were relatively homogeneous, distinct HVR
      variants were observed in each anti-D recipient, indicating that this region can
      evolve in multiple directions from the same point. Where HVR variants with
      dissimilar sequences were present in a single individual, the frequency of
      synonymous substitution in the flanking regions suggested that the lineages
      diverged more than a decade previously. Even where a single major HVR variant was
      present in an infected individual, this lineage was usually several years old.
      Multiple lineages can therefore coexist during long periods of chronic infection
      without replacement. The characteristics of amino acid substitution in the HVR
      were not consistent with the random accumulation of mutations and imply that
      amino acid replacement in the HVR was strongly constrained. Another variable
      region of E2 centered on codon 60 shows similar constraints, while HVR2 was
      relatively unconstrained. Several of these features are difficult to explain if a
      neutralizing immune response against the HVR is the only selective force
      operating on E2. The impact of PCR artifacts such as nucleotide misincorporation
      and the shuffling of dissimilar templates is discussed.

PMID- 9573259
TI  - Transmissible gastroenteritis coronavirus induces programmed cell death in
      infected cells through a caspase-dependent pathway.
AB  - In this report, we show that apoptosis (or programmed cell death) is induced in
      different cell lines infected with a coronavirus, the porcine transmissible
      gastroenteritis virus (TGEV). Kinetic analysis of internucleosomal DNA cleavage
      by agarose gel electrophoresis and flow cytometry or cytometric monitoring of the
      mitochondrial transmembrane potential showed that, for ST cells infected with
      TGEV, the first overt signs of apoptosis appeared from 10 to 12 h postinfection
      on. They preceded morphological changes characteristic of cells undergoing
      apoptosis, as observed by light and electron microscopy. The tripeptide pan-ICE
      (caspase) inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone blocked
      TGEV-induced apoptosis with no effect on virus production. The thiol agent
      pyrrolidine dithiocarbamate inhibited apoptosis, suggesting that TGEV infection
      may lead to apoptosis via cellular oxidative stress. The effect of TGEV infection
      on activation of NF-kappaB, a transcription factor known to be activated by
      oxidative stress, was examined. NF-kappaB DNA binding was shown to be strongly
      and quickly induced by TGEV infection. However, transcription factor decoy
      experiments showed that NF-kappaB activation is not critical for TGEV-induced
      apoptosis.

PMID- 9573258
TI  - Transcription factor YY1 represses cell-free replication from human
      papillomavirus origins.
AB  - We have established cell-free replication for the human papillomavirus type 18
      (HPV-18) origin of replication (ori)-containing DNA by using purified HPV-18 E1
      and E2 gene products expressed as fusion proteins in Escherichia coli. The
      transcription factor YY1 has been shown to regulate RNA transcription by binding
      to a sequence overlapping the putative E1 protein binding site in the HPV-18 ori.
      We show that exogenously added YY1 fusion protein inhibited HPV-18 ori
      replication. Cotransfection of YY1 expression vectors also inhibited transient
      replication in 293 cells. However, inhibition did not appear to be mediated by
      binding to its cognate site in the ori as YY1 also inhibited the replication of
      the HPV-11 ori, which does not have a known or suspected YY1 binding site.
      Moreover, inhibition was not alleviated by the inclusion of YY1 binding
      oligonucleotides in the replication reaction mixtures. Rather, we demonstrated a
      direct interaction between purified fusion E2 protein and fusion YY1 protein by
      the pull-down assay and a partial restoration of replication activity by an
      elevated E2 protein concentration. These results suggest that YY1 can inhibit HPV
      ori replication by interfering with E2 protein functions.

PMID- 9573260
TI  - Induction of protective immunity against Japanese encephalitis in mice by
      immunization with a plasmid encoding Japanese encephalitis virus premembrane and
      envelope genes.
AB  - A DNA vaccine plasmid containing the Japanese encephalitis (JE) virus premembrane
      (prM) and envelope (E) genes (designated pcDNA3JEME) was evaluated for
      immunogenicity and protective efficacy in mice. Two immunizations of 4-week-old
      female ICR mice with pcDNA3JEME by intramuscular or intradermal injections at a
      dose of 10 or 100 microg per mouse elicited neutralizing (NEUT) antibodies at
      titers of 1:10 to 1:20 (90% plaque reduction), and all immunized mice survived a
      challenge with 10,000 50% lethal doses of the P3 strain of JE virus. A single
      immunization with 100 microg of pcDNA3JEME did not elicit detectable NEUT
      antibodies but induced protective immunity. Spleen cells obtained from BALB/c
      mice immunized once with 10 or 100 microg of pcDNA3JEME contained JE virus
      specific memory cytotoxic T lymphocytes (CTLs). BALB/c mice maintained detectable
      levels of memory B cells and CTLs for at least 6 months after one immunization
      with pcDNA3JEME at a dose of 100 microg. The CTLs induced in BALB/c mice
      immunized twice with 100 microg of pcDNA3JEME were CD8 positive and recognized
      mainly the envelope protein. These results indicate that pcDNA3JEME has the
      ability to induce a protective immune response which includes JE virus-specific
      antibodies and CTLs.

PMID- 9573262
TI  - Herpes simplex virus type 1 glycoprotein B requires a cysteine residue at
      position 633 for folding, processing, and incorporation into mature infectious
      virus particles.
AB  - Herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) resides in the virus
      envelope in an oligomeric form and plays an essential role in virus entry into
      susceptible host cells. The oligomerizing domain is a movable element consisting
      of amino acids 626 to 653 in the gB external domain. This domain contains a
      single cysteine residue at position 633 (Cys-633) that is predicted to form an
      intramolecular disulfide bridge with Cys-596. In this study, we examined gB
      oligomerization, processing, and incorporation into mature virus during infection
      by two mutant viruses in which either the gB Cys-633 [KgB(C633S)] or both Cys-633
      and Cys-596 [KgB(C596S/C633S)] residues were mutated to serine. The result of
      immunofluorescence studies and analyses of released virus particles showed that
      the mutant gB molecules were not transported to the cell surface or incorporated
      into mature virus envelopes and thus infectious virus was not produced.
      Immunoprecipitation studies revealed that the mutant gB molecules were in an
      oligomeric configuration and that these mutants produced hetero-oligomers with a
      truncated form of gB consisting of residues 1 to 43 and 595 to 904, the latter
      containing the oligomerization domain. Pulse-chase experiments in combination
      with endoglycosidase H treatment determined that the mutant molecules were
      improperly processed, having been retained in the endoplasmic reticulum (ER).
      Coimmunoprecipitation experiments revealed that the cysteine mutations resulted
      in gB misfolding and retention by the molecular chaperones calnexin,
      calreticulin, and Grp78 in the ER. The altered conformation of the gB mutant
      glycoproteins was directly detected by a reduction in monoclonal antibody
      recognition of two previously defined distinct antigenic sites located within
      residues 381 to 441 and 595 to 737. The misfolded molecules were not transported
      to the cell surface as hetero-oligomers with wild-type gB, suggesting that the
      conformational change could not be corrected by intermolecular interactions with
      the wild-type molecule. Together, these experiments confirmed that a disulfide
      bridge involving Cys-633 and Cys-596 is not essential for oligomerization but
      rather is required for proper folding and maintenance of a gB domain essential to
      complete posttranslational modification, transport, and incorporation into mature
      virus particles.

PMID- 9573263
TI  - L* protein of the DA strain of Theiler's murine encephalomyelitis virus is
      important for virus growth in a murine macrophage-like cell line.
AB  - Strain GDVII and other members of the GDVII subgroup of Theiler's murine
      encephalomyelitis virus (TMEV) are highly virulent and cause acute
      polioencephalomyelitis in mice. Neither viral persistence nor demyelination is
      demonstrated in the few surviving mice. On the other hand, strain DA and other
      members of the TO subgroup of TMEV are less virulent and establish a persistent
      infection in the spinal cord, which results in a demyelinating disease. We
      previously reported that GDVII does not actively replicate in a murine macrophage
      like cell line, J774-1, whereas DA strain productively infects these cells (M.
      Obuchi, Y. Ohara, T. Takegami, T. Murayama, H. Takada, and H. Iizuka, J. Virol.
      71:729-733, 1997). In the present study, we used recombinant viruses between
      these strains of the two subgroups to demonstrate that the DA L coding region of
      DA strain is important for virus growth in J774-1 cells. Additional experiments
      with a mutant virus indicate that L* protein, which is synthesized out of frame
      with the polyprotein from an additional alternative initiation codon in the L
      coding region of TO subgroup strains, is a key determinant responsible for the
      cell-type-specific restriction of virus growth. L* protein may play a critical
      role in the DA-induced restricted demyelinating infection by allowing growth in
      macrophages, a major site for virus persistence.

PMID- 9573261
TI  - Induction of systemic and mucosal immune responses to human immunodeficiency
      virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via
      intramuscular and intranasal routes.
AB  - Induction of mucosal and cell-mediated immunity is critical for development of an
      effective vaccine against human immunodeficiency virus (HIV). We compared
      intramuscular and intranasal immunizations with a DNA vaccine encoding env of HIV
      1 and evaluated the QS-21 saponin adjuvant for augmentation of the systemic and
      mucosal immune responses to HIV-1 in a murine model. Vaccination via the two
      routes elicited comparable systemic immune responses, and QS-21 consistently
      enhanced antigen-specific serum immunoglobulin G2a (IgG2a) production, delayed
      type hypersensitivity reaction, and cytolytic activity of splenocytes. Intestinal
      secretory IgA production and cytolytic activity of the mesenteric lymph node
      cells are preferentially elicited by intranasal immunization, and QS-21 augmented
      these activities as well. This adjuvant augmented production of interleukin-2 (IL
      2) and gamma interferon (IFN-gamma) associated with decrease in IL-4 synthesis by
      antigen-restimulated splenocytes. The serum immunoglobulin subtype profile showed
      a dominant IgG2a response and less strong IgG1 and IgE production in a QS-21 dose
      dependent manner. As expected, enhancements of humoral and cell-mediated immune
      responses by QS-21 were abrogated by treatment with anti-IL-2 and anti-IFN-gamma
      monoclonal antibodies. These results suggest that the intranasal route of DNA
      immunization is more efficient than the intramuscular route in inducing mucosal
      immunity mediated by sIgA and mesenteric lymphocytes. Furthermore, QS-21 is able
      to act as a mucosal adjuvant in DNA vaccination and demonstrates its
      immunomodulatory property via stimulation of the Th1 subset. This study
      emphasizes the importance of the route of immunization and the use of an adjuvant
      for effective DNA vaccination against HIV-1.

PMID- 9573264
TI  - Entry of amphotropic murine leukemia virus is influenced by residues in the
      putative second extracellular domain of its receptor, Pit2.
AB  - Human cells express distinct but related receptors for the gibbon ape leukemia
      virus (GALV) and the amphotropic murine leukemia virus (A-MuLV), termed Pit1 and
      Pit2, respectively. Pit1 is not able to function as a receptor for A-MuLV
      infection, while Pit2 does not confer susceptibility to GALV. Previous studies of
      chimeric receptors constructed by interchanging regions of Pit1 and Pit2 failed
      to clarify the determinants unique to Pit2 which correlate with A-MuLV receptor
      function. In order to identify which regions of Pit2 are involved in A-MuLV
      receptor function, we exchanged the putative second and third extracellular
      domains of Pit1, either individually or together, with the corresponding regions
      of Pit2. Our functional characterization of these receptors indicates a role for
      the putative second extracellular domain (domain II) in A-MuLV infection. We
      further investigated the influence of domain II with respect to A-MuLV receptor
      function by performing site-specific mutagenesis within this region of Pit2. Many
      of the mutations had little or no effect on receptor function. However, the
      substitution of serine for methionine at position 138 (S138M) in a Pit1 chimera
      containing domain II of Pit2 resulted in a 1,000-fold reduction in A-MuLV
      receptor function. Additional mutations made within domain II of the
      nonfunctional S138M mutant restored receptor function to nearly wild-type
      efficiency. The high degree of tolerance for mutations as well as the
      compensatory effect of particular substitutions observed within domain II
      suggests that an element of secondary structure within this region plays a
      critical role in the interaction of the receptor with A-MuLV.

PMID- 9573265
TI  - Expression of CCR5 increases during monocyte differentiation and directly
      mediates macrophage susceptibility to infection by human immunodeficiency virus
      type 1.
AB  - The stage of differentiation and the lineage of CD4+ cells profoundly affect
      their susceptibility to infection by human immunodeficiency virus type 1 (HIV-1).
      While CD4(+) T lymphocytes in patients are readily susceptible to HIV-1
      infection, peripheral blood monocytes are relatively resistant during acute or
      early infection, even though monocytes also express CD4 and viral strains with
      macrophage (M)-tropic phenotypes predominate. CCR5, the main coreceptor for M
      tropic viruses, clearly contributes to the ability of CD4+ T cells to be
      infected. To determine whether low levels of CCR5 expression account for the
      block in infection of monocytes, we examined primary monocyte lineage cells
      during differentiation. Culturing of blood monocytes for 5 days led to an
      increase in the mean number of CCR5-positive cells from <20% of monocytes to >80%
      of monocyte-derived macrophages (MDM). Levels of CCR5 expression per monocyte
      were generally lower than those on MDM, perhaps below a minimum threshold level
      necessary for efficient infection. Productive infection may be restricted to the
      small subset of monocytes that express relatively high levels of CCR5. Steady
      state CCR5 mRNA levels also increased four- to fivefold during MDM
      differentiation. Infection of MDM by M-tropic HIV-1JRFL resulted in >10-fold
      higher levels of p24, and MDM harbored >30-fold more HIV-1 DNA copies than
      monocytes. In the presence of the CCR5-specific monoclonal antibody (MAb) 2D7,
      virus production and cellular levels of HIV-1 DNA were decreased by >80% in MDM,
      indicating a block in viral entry. There was a direct association between levels
      of CCR5 and differentiation of monocytes to macrophages. Levels of CCR5 were
      related to monocyte resistance and macrophage susceptibility to infection because
      infection by the M-tropic strain HIV-1JRFL could be blocked by MAb 2D7. These
      results provide direct evidence that CCR5 functions as a coreceptor for HIV-1
      infection of primary macrophages.

PMID- 9573266
TI  - Permissive cytomegalovirus infection of primary villous term and first trimester
      trophoblasts.
AB  - Forty percent of women with primary cytomegalovirus (CMV) infections during
      pregnancy infect their fetuses with complications for the baby varying from mild
      to severe. How CMV crosses the syncytiotrophoblast, the barrier between maternal
      blood and fetal tissue in the villous placenta, is unknown. Virus may cross by
      infection of maternal cells that pass through physical breaches in the
      syncytiotrophoblast or by direct infection of the syncytiotrophoblast, with
      subsequent transmission to underlying fetal placental cells. In this study, we
      show that pure (>99.99%), long-term and healthy (>3 weeks) cultures of
      syncytiotrophoblasts are permissively infected with CMV. Greater than 99% of
      infectious progeny virus remained cell associated throughout culture periods up
      to 3 weeks. Infection of term trophoblasts required a higher virus inoculum, was
      less efficient, and progressed more slowly than parallel infections of placental
      and human embryonic lung fibroblasts. Three laboratory strains (AD169, Towne, and
      Davis) and a clinical isolate from a congenitally infected infant all
      permissively infected trophoblasts, although infection efficiencies varied. The
      infection of first trimester syncytiotrophoblasts with strain AD169 occurred at
      higher frequency and progressed more rapidly than infection of term cells but
      less efficiently and rapidly than infection of fibroblasts. These results show
      that villous syncytiotrophoblasts can be permissively infected by CMV but that
      the infection requires high virus titers and proceeds slowly and that progeny
      virus remains predominantly cell associated.

PMID- 9573267
TI  - Identification of kaposin (open reading frame K12) as a human herpesvirus 8
      (Kaposi's sarcoma-associated herpesvirus) transforming gene.
AB  - The recently identified human herpesvirus 8 (HHV-8, or Kaposi's sarcoma
      associated herpesvirus) has been implicated in the etiology of both Kaposi's
      sarcoma (KS) and primary effusion (body cavity-based) lymphoma (PEL) (Y. Chang et
      al., Science 266:1865-1869, 1994; P. S. Moore et al., J. Virol. 70:549-558,
      1996). An important feature of the association of HHV-8 with these malignancies
      is the expression of an abundant, latency-associated 0.7-kb transcript, T0. 7 (W.
      Zhong et al., Proc. Natl. Acad. Sci. USA 93:6641-6646, 1996). T0.7 is found in
      all stages in nearly all KS tumors of different epidemiologic origin, including
      AIDS-associated, African endemic, and classical KS (K. A. Staskus et al., J.
      Virol. 71:715-719, 1997), as well as in a body cavity-based lymphoma-derived cell
      line, BCBL-1, that is latently infected with HHV-8 (R. Renne et al., Nat. Med.
      2:342-346, 1996). T0.7 encodes a unique HHV-8 open reading frame, K12, also known
      as kaposin. In this study, we report that the kaposin gene induced tumorigenic
      transformation. Constructs with kaposin expressed either from its endogenous
      promoter or from a heterologous promoter induced focal transformation upon
      transfection into Rat-3 cells. All transformed Rat-3 cell lines containing
      kaposin sequences produced high-grade, highly vascular, undifferentiated sarcomas
      upon subcutaneous injection of athymic nu/nu mice. Tumor-derived cell lines
      expressed kaposin mRNA, suggesting a role in the maintenance of the transformed
      phenotype. Furthermore, kaposin protein was detected in transformed and tumor
      derived cells by immunofluorescence and localized to the cytoplasm. More
      importantly, expression of kaposin protein was also detected in the PEL cell
      lines BCBL-1 and KS-1. These findings demonstrate the oncogenic potential of
      kaposin and suggest its possible role in the development of KS and other HHV-8
      associated malignancies.

PMID- 9573268
TI  - Human cytomegalovirus oriLyt sequence requirements.
AB  - The mechanisms of action and regulation of the human cytomegalovirus (HCMV) lytic
      phase DNA replicator, oriLyt, which spans more than 2 kbp in a structurally
      complex region near the middle of the unique long region (UL), are not
      understood. Because oriLyt is thought to be essential for promoting initiation of
      lytic DNA synthesis and may participate in regulating the switch between lytic
      and latent phases, we undertook a mutational study to better define its sequence
      requirements. Kanr gene cassette insertions located an oriLyt core region between
      nucleotides (nt) 91751 and 93299 that is necessary but not sufficient for
      replicator activity in transient assays. In contrast, insertions into auxiliary
      regions flanking either side of this core-also required for significant
      replicator activity-had little effect. To search for essential components within
      the core region, we made a series of overlapping, roughly 200-bp deletions, and
      qualitatively and quantitatively assessed the abilities of the resulting
      constructs to mediate replication. All but one of these deletions produced a
      significant (i.e., greater than twofold) loss of activity, arguing that sequences
      across this entire region contribute to replicator function. However, two
      particularly critical segments separated by a dispensable region, here called
      essential regions I and II, were identified. Within essential region I, which
      overlaps the previously identified early transcript SRT, two adjacent but
      nonoverlapping, roughly 200-bp deletions abolished detectable replication. No
      single element or motif from the left half of essential region I was found to be
      essential. Thus, essential region I probably promotes replication through the
      cooperation of multiple elements. However, four small deletions in the right half
      of essential region I, which included or lay adjacent to the conserved 31-nt
      oligopyrimidine tract (referred to as the Y block), abolished or virtually
      abolished oriLyt activity. Together, these results identify candidate oriLyt
      sequences within which molecular interactions essential for initiation of oriLyt
      mediated DNA synthesis are likely to occur.

PMID- 9573269
TI  - Mapping of homologous interaction sites in the hepatitis B virus core protein.
AB  - Hepatitis B virus consists of an outer envelope and an inner capsid, or core,
      that wraps around the small genome plus the viral replication enzyme. The
      icosahedrally symmetric nucleocapsid is assembled from multiple dimeric subunits
      of a single 183-residue capsid protein, which must therefore contain interfaces
      for monomer dimerization and for dimer multimerization. The atomic structure of
      the protein is not known, but electron microscopy-based image reconstructions
      suggested a hammerhead shape for the dimer and, very recently, led to a tentative
      model for the main chain trace. Here we used a combination of interaction
      screening techniques and functional analyses of core protein variants to define,
      at the primary sequence level, the regions that mediate capsid assembly. Both the
      two-hybrid system and the pepscan technique identified a strongly interacting
      region I between amino acids (aa) 78 and 117 that probably forms part of the
      dimer interface. Surprisingly, mutations in this region, in the context of a C
      terminally truncated but assembly-competent core protein variant, had no
      detectable effect on assembly. By contrast, mutations in a second region,
      bordered by aa 113 and 143, markedly influenced capsid stability, strongly
      suggesting that this region II is the main contributor to dimer multimerization.
      Based on the electron microscopic data, it must therefore be located at the basal
      tips of the dimer, experimentally supporting the proposed main chain trace.

PMID- 9573270
TI  - Cytomegalovirus inhibits the engraftment of donor bone marrow cells by
      downregulation of hemopoietin gene expression in recipient stroma.
AB  - Cytomegalovirus (CMV) disease after bone marrow (BM) transplantation is often
      associated with BM graft failure. There are two possible reasons for such a
      correlation. First, a poor hematopoietic reconstitution of unrelated etiology
      could promote the progression of CMV infection by the lack of immune control.
      Alternatively, CMV infection could interfere with the engraftment of donor BM
      cells in recipient BM stroma. Evidence for a causative role of CMV in BM aplasia
      came from studies in long-term BM cultures and from the murine in vivo model of
      CMV-induced aplastic anemia. A deficiency in the expression of essential stromal
      hemopoietins, such as stem cell factor (SCF), has indicated a functional
      insufficiency of the stromal microenvironment. It remained open to question
      whether CMV mediates a negative regulation of hemopoietin gene expression (the
      downregulation model) or whether it causes the default of a positive regulator
      (the lack-of-induction model). Further, even though implicitly assumed, it has
      never been formally documented that CMV directly interferes with the engraftment
      of a BM cell transplant. We addressed these problems in a murine model of CMV
      infection after experimental male-into-female BM transplantation. The data
      indicate that the downregulation model applies. Quantitation of the male-sex
      determining gene tdy demonstrated an impaired engraftment of donor BM cells in
      the BM stroma of the female recipients. This graft failure was reflected by a
      diminished population of SCF-receptor-expressing hematopoietic progenitor cells
      and correlated with a reduced level of stromal SCF gene expression.
      Interestingly, high doses of BM cells protected against stromal insufficiency by
      a mechanism unrelated to control of infection.

PMID- 9573271
TI  - Activation of papillomavirus late gene transcription and genome amplification
      upon differentiation in semisolid medium is coincident with expression of
      involucrin and transglutaminase but not keratin-10.
AB  - The life cycle of the papillomaviruses is closely linked to host cell
      differentiation, as demonstrated by the fact that amplification of viral DNA and
      transcription of late genes occur only in the suprabasal cells of a
      differentiated epithelium. Previous studies examining the pathogenesis of
      papillomavirus infections have relied on the use of organotypic raft cultures or
      lesions from patients to examine these differentiation-dependent viral
      activities. In this study, we used a simple system for epithelial differentiation
      to study human papillomavirus (HPV) late functions. We demonstrate that the
      suspension of HPV-infected keratinocytes in semisolid medium containing 1.6%
      methylcellulose for 24 h was sufficient for the activation of the late promoter,
      transcription of late genes, and amplification of viral DNA. These activities
      were shown to be linked to and coincide with cellular differentiation. Expression
      of the late protein E1(wedge)E4 and amplification of viral DNA were detected in
      the identical set of cells after suspension in methylcellulose. This technique
      was also used to analyze the differentiation properties of the cells which
      expressed the late protein E1(wedge)E4. While induction of the spinous layer
      markers involucrin and transglutaminase was compatible with late promoter
      induction, expression of the differentiation-specific keratin-10 was shown not to
      be required for HPV late functions. Interestingly, while the majority of normal
      human keratinocytes induced filaggrin expression by 24 h, this marker of the
      granular layer was induced in a smaller subset of HPV type 31 (HPV-31)-positive
      cells at this time point. The HPV-31-positive cells which expressed filaggrin did
      not induce the late protein E1(wedge)E4. Use of the methylcellulose system to
      induce epithelial differentiation coupled with the ability to perform a genetic
      analysis of HPV functions by using transfection of cloned viral DNA will
      facilitate the study of the regulation of the papillomavirus life cycle.

PMID- 9573272
TI  - Site-specific integration in mammalian cells mediated by a new hybrid baculovirus
      adeno-associated virus vector.
AB  - Baculovirus can transiently transduce primary human and rat hepatocytes, as well
      as a subset of stable cell lines. To prolong transgene expression, we have
      developed new hybrid vectors which associate key elements from adeno-associated
      virus (AAV) with the elevated transducing capacity of baculovirus. The hybrid
      vectors contain a transgene cassette composed of the beta-galactosidase (beta
      Gal) reporter gene and the hygromycin resistance (Hygr) gene flanked by the AAV
      inverted terminal repeats (ITRs), which are necessary for AAV replication and
      integration in the host genome. Constructs were derived both with and without the
      AAV rep gene under the p5 and p19 promoters cloned in different positions with
      respect to the baculovirus polyheidrin promoter. A high-titer preparation of
      baculovirus-AAV (Bac-AAV) chimeric virus containing the ITR-Hygr-beta-Gal
      sequence was obtained with insect cells only when the rep gene was placed in an
      antisense orientation to the polyheidrin promoter. Infection of 293 cells with
      Bac-AAV virus expressing the rep gene results in a 10- to 50-fold increase in the
      number of Hygr stable cell clones. Additionally, rep expression determined the
      localization of the transgene cassette in the aavs1 site in approximately 41% of
      cases as detected by both Southern blotting and fluorescent in situ hybridization
      analysis. Moreover, site-specific integration of the ITR-flanked DNA was also
      detected by PCR amplification of the ITR-aavs1 junction in transduced human
      fibroblasts. These data indicate that Bac-AAV hybrid vectors can allow permanent,
      nontoxic gene delivery of DNA constructs for ex vivo treatment of primary human
      cells.

PMID- 9573273
TI  - In vivo distribution of the human immunodeficiency virus/simian immunodeficiency
      virus coreceptors: CXCR4, CCR3, and CCR5.
AB  - We have evaluated the in vivo distribution of the major human immunodeficiency
      virus/simian immunodeficiency virus (HIV/SIV) coreceptors, CXCR4, CCR3, and CCR5,
      in both rhesus macaques and humans. T lymphocytes and macrophages in both
      lymphoid and nonlymphoid tissues are the major cell populations expressing
      HIV/SIV coreceptors, reaffirming that these cells are the major targets of
      HIV/SIV infection in vivo. In lymphoid tissues such as the lymph node and the
      thymus, approximately 1 to 10% of the T lymphocytes and macrophages are
      coreceptor positive. However, coreceptor expression was not detected on
      follicular dendritic cells (FDC) in lymph nodes, suggesting that the ability of
      FDC to trap extracellular virions is unlikely to be mediated by a coreceptor
      specific mechanism. In the thymus, a large number of immature and mature T
      lymphocytes express CXCR4, which may render these cells susceptible to infection
      by syncytium-inducing viral variants that use this coreceptor for entry. In
      addition, various degrees of coreceptor expression are found among different
      tissues and also among different cells within the same tissues. Coreceptor
      positive cells are more frequently identified in the colon than in the rectum and
      more frequently identified in the cervix than in the vagina, suggesting that the
      expression levels of coreceptors are differentially regulated at different
      anatomic sites. Furthermore, extremely high levels of CXCR4 and CCR3 expression
      are found on the neurons from both the central and peripheral nervous systems.
      These findings may be helpful in understanding certain aspects of HIV and SIV
      pathogenesis and transmission.

PMID- 9573274
TI  - Effects of mutations in residues near the active site of human immunodeficiency
      virus type 1 integrase on specific enzyme-substrate interactions.
AB  - The phylogenetically conserved catalytic core domain of human immunodeficiency
      virus type 1 (HIV-1) integrase contains elements necessary for specific
      recognition of viral and target DNA features. In order to identify specific amino
      acids that determine substrate specificity, we mutagenized phylogenetically
      conserved residues that were located in close proximity to the active-site
      residues in the crystal structure of the isolated catalytic core domain of HIV-1
      integrase. Residues composing the phylogenetically conserved DD(35)E active-site
      motif were also mutagenized. Purified mutant proteins were evaluated for their
      ability to recognize the phylogenetically conserved CA/TG base pairs near the
      viral DNA ends and the unpaired dinucleotide at the 5' end of the viral DNA,
      using disintegration substrates. Our findings suggest that specificity for the
      conserved A/T base pair depends on the active-site residue E152. The phenotype of
      IN(Q148L) suggested that Q148 may be involved in interactions with the 5'
      dinucleotide of the viral DNA end. The activities of some of the proteins with
      mutations in residues in close proximity to the active-site aspartic and glutamic
      acids were salt sensitive, suggesting that these mutations disrupted interactions
      with DNA.

PMID- 9573275
TI  - Mechanism of injury-provoked poliomyelitis.
AB  - Skeletal muscle injury is known to predispose its sufferers to neurological
      complications of concurrent poliovirus infections. This phenomenon, labeled
      "provocation poliomyelitis," continues to cause numerous cases of childhood
      paralysis due to the administration of unnecessary injections to children in
      areas where poliovirus is endemic. Recently, it has been reported that
      intramuscular injections may also increase the likelihood of vaccine-associated
      paralytic poliomyelitis in recipients of live attenuated poliovirus vaccines. We
      have studied this important risk factor for paralytic polio in an animal system
      for poliomyelitis and have determined the pathogenic mechanism linking
      intramuscular injections and provocation poliomyelitis. Skeletal muscle injury
      induces retrograde axonal transport of poliovirus and thereby facilitates viral
      invasion of the central nervous system and the progression of spinal cord damage.
      The pathogenic mechanism of provocation poliomyelitis may differ from that of
      polio acquired in the absence of predisposing factors.

PMID- 9573276
TI  - Template-independent repair of the 3' end of cucumber mosaic virus satellite RNA
      controlled by RNAs 1 and 2 of helper virus.
AB  - RNA viruses which do not have a poly(A) tail or a tRNA-like structure for the
      protection of their vulnerable 3' termini may have developed a different strategy
      to maintain their genome integrity. We provide evidence that deletions of up to 7
      nucleotides from the 3' terminus of cucumber mosaic cucumovirus (CMV) satellite
      RNA (satRNA) were repaired in planta in the presence of the helper virus (HV)
      CMV. Sequence comparison of 3'-end-repaired satRNA progenies, and of satRNA and
      HV RNA, suggested that the repair was not dependent on a viral template. The 3'
      end of CMV satRNA lacking the last three cytosines was not repaired in planta in
      the presence of tomato aspermy cucumovirus (TAV), although TAV is an efficient
      helper for the replication of CMV satRNA. With use of pseudorecombinants
      constructed by the interchange of RNAs 1 and 2 of TAV and CMV, evidence was
      provided that the 3'-end repair was controlled by RNAs 1 and 2 of CMV, which
      encode subunits of the viral RNA replicase. These results, and the observation of
      short repeated sequences close to the 3' terminus of repaired molecules, suggest
      that the HV replicase maintains the integrity of the satRNA genome, playing a
      role analogous to that of cellular telomerases.

PMID- 9573277
TI  - Herpes simplex virus type 1 latency-associated transcripts suppress viral
      replication and reduce immediate-early gene mRNA levels in a neuronal cell line.
AB  - During herpes simplex virus type 1 (HSV-1) latent infection in human dorsal root
      ganglia, limited viral transcription, which has been linked to HSV-1 reactivation
      ability, takes place. To study the involvement of this transcription in HSV-1
      replication in neuronal cells and consequently in viral latency, we constructed
      stably transfected neuronal cell lines containing (i) the entire HSV-1 latency
      transcriptionally active DNA fragment, (ii) the same DNA sequence with deletions
      of the latency-associated transcript (LAT) promoters, or (iii) the DNA coding
      sequence of the LAT domain. Replication of HSV-1 or a LAT-negative mutant was
      markedly repressed in the LAT-expressing cells, a phenomenon mediated by the
      LATs. To study the mechanism responsible for this effect, we examined LAT
      influence upon expression of HSV-1 immediate-early (IE) genes ICP0, ICP4, and
      ICP27, by Northern blot analysis. Following infection of a LAT-expressing
      neuronal cell line with a LAT-negative mutant, the steady-state levels of all
      three IE mRNAs were reduced compared to those for control cells. Transient
      transfections into a neuronal cell line indicated that the LAT suppressive effect
      upon ICP0 mRNA was mediated directly and was not due to the LAT effect upon the
      ICP0 promoter. We therefore propose that the LATs may repress viral replication
      in neuronal cells by reducing IE gene mRNA levels and thus facilitate the
      establishment of HSV-1 latency in nervous tissue.

PMID- 9573278
TI  - Inhibition of major histocompatibility complex class I antigen presentation in
      pig and primate cells by herpes simplex virus type 1 and 2 ICP47.
AB  - Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) express an immediate-early
      protein, ICP47, that effectively inhibits the human transporter associated with
      antigen presentation (TAP), blocking major histocompatibility complex (MHC) class
      I antigen presentation to CD8+ T cells. Previous work indicated that the mouse
      TAP is relatively resistant to inhibition by the HSV-1 and HSV-2 ICP47 proteins
      (ICP47-1 and ICP47-2) and that mouse cells infected with HSV-1 are lysed by anti
      HSV CD8+ cytotoxic T lymphocytes (CTL). Therefore, mice are apparently not
      suitable animals in which to study the in vivo effects of ICP47. In order to find
      an animal model, we introduced ICP47-1 and ICP47-2 into cells from various animal
      species-mice, rats, guinea pigs, rabbits, dogs, pigs, cows, monkeys, and humans
      and measured TAP activity in the cells. Both proteins were unable to inhibit TAP
      in mouse, rat, guinea pig, and rabbit cells. In contrast, ICP47-1 and ICP47-2
      inhibited TAP in pig, dog, cow, and monkey cells, and the TAP in pig and dog
      fibroblasts was often more sensitive to both proteins than TAP in human
      fibroblasts. These results were extended by measuring CD8+-T-cell recognition
      (CTL lysis) of cells from various species. Cells were infected with recombinant
      HSV-1 constructed to express murine MHC class I proteins so that the cells would
      be recognized and lysed by well-characterized murine anti-HSV CTL unless antigen
      presentation was blocked by ICP47. Anti-HSV CD8+ CTL effectively lysed pig and
      primate cells infected with a recombinant HSV-1 ICP47- mutant but were unable to
      lyse pig or primate cells infected with a recombinant HSV-1 that expressed ICP47.
      Therefore, pigs, dogs, and monkeys may be useful animal models in which to test
      the effects of ICP47 on HSV pathogenesis or the use of ICP47 as a selective
      immunosuppressive agent.

PMID- 9573279
TI  - Woodchuck hepatitis virus contains a tripartite posttranscriptional regulatory
      element.
AB  - The hepatitis B virus posttranscriptional regulatory element (HBVPRE) is a cis
      acting RNA element that partially overlaps with enhancer I and is required for
      the cytoplasmic accumulation of HBV surface RNAs. We find that the closely
      related woodchuck hepatitis virus (WHV), which has been shown to lack a
      functional enhancer I, also contains a posttranscriptional regulatory element
      (WPRE). Deletion analysis suggests that the WPRE consists of three independent
      subelements. Comparison of the bipartite HBVPRE and tripartite WPRE activities
      reveals that the tripartite WPRE is two to three times more active than the
      bipartite HBVPRE. Mutation of a single WPRE subelement decreases WPRE activity to
      the level of the HBVPRE. Bipartite and tripartite chimeras of the WPRE and HBVPRE
      possess activities which suggest that elements containing three subelements are
      posttranscriptionally stronger than those containing two. These data demonstrate
      that the posttranscriptional regulatory element is conserved within the mammalian
      hepadnaviruses and that its strength is determined by the number of subelements
      within the RNA.

PMID- 9573280
TI  - A novel polymorphism at codon 333 of human immunodeficiency virus type 1 reverse
      transcriptase can facilitate dual resistance to zidovudine and L-2',3'-dideoxy-3'
      thiacytidine.
AB  - Recent clinical trials examining 3'-azido-3'-deoxythymidine (AZT, zidovudine, or
      Retrovir) combined with L-2', 3'-dideoxy-3'-thiacytidine (3TC or lamivudine) have
      shown that combination therapy with these nucleoside analogs affords significant
      virological and clinical benefits. The addition of 3TC to AZT delays AZT
      resistance in therapy-naive patients and can restore viral AZT susceptibility in
      patients who previously received AZT alone. In some AZT-experienced patients, the
      virological response to AZT-3TC therapy is not sustained and virus resistant to
      both drugs can be identified. To gain insight into the possible mechanism of dual
      resistance, we studied a recently described variant resistant to both AZT and 3TC
      and obtained by simultaneous passage of an AZT-resistant clinical isolate in cell
      culture with AZT and 3TC. Genetic mapping and site-directed mutagenesis
      experiments demonstrated that a polymorphism at codon 333 (Gly to Glu) of human
      immunodeficiency virus type 1 reverse transcriptase (RT) was critical in
      facilitating dual resistance in a complex background of AZT and 3TC resistance
      mutations. To assess the potential clinical relevance of RT codon 333 changes, we
      studied dually resistant viruses from patients taking AZT and 3TC. Genetic
      mapping of RT molecular clones derived from patients' plasma samples demonstrated
      that in some cases polymorphism at codon 333 was responsible for facilitating
      dual resistance.

PMID- 9573281
TI  - Evolution of syncytium-inducing and non-syncytium-inducing biological virus
      clones in relation to replication kinetics during the course of human
      immunodeficiency virus type 1 infection.
AB  - To investigate the temporal relationship between human immunodeficiency virus
      type 1 (HIV-1) replicative capacity and syncytium-inducing (SI) phenotype,
      biological and genetic characteristics of longitudinally obtained virus clones
      from two HIV-1-infected individuals who developed SI variants were studied. In
      one individual, the emergence of rapidly replicating SI and non-syncytium
      inducing (NSI) variants was accompanied by a loss of the slowly replicating NSI
      variants. In the other subject, NSI variants were always slowly replicating,
      while the coexisting SI variants showed an increase in the rate of replication.
      Irrespective their replicative capacity, the NSI variants remained present
      throughout the infection in both individuals. Phylogenetic analysis of the V3
      region showed early branching of the SI variants from the NSI tree. Successful SI
      conversion seemed a unique event since no SI variants were found among later
      stage NSI variants. This was also confirmed by the increasing evolutionary
      distance between the two subpopulations. At any time point during the course of
      the infection, the variation within the coexisting SI and NSI populations did not
      exceed 2%, indicating continuous competition within each viral subpopulation.

PMID- 9573282
TI  - Analysis of a vaccinia virus mutant expressing a nonpalmitylated form of p37, a
      mediator of virion envelopment.
AB  - Vaccinia virus encodes a 37-kDa palmitylated protein (p37) that is required for
      envelopment, translocation, and cell-to-cell spread of virions. We have analyzed
      the biological significance of the palmitate modification by constructing a
      recombinant vaccinia virus that expresses a nonpalmitylated p37 and comparing its
      biological activity to that of the wild-type virus. The mutant virus is
      inefficient at cell-to-cell spread and does not produce or release enveloped
      virions, although it produces normal amounts of nonenveloped virions.
      Furthermore, the mutant virus is not able to nucleate actin to propel itself
      through and out of the cell, a function requiring the indirect participation of
      p37. The deficiency in protein function appears to result from a lack of
      appropriate targeting to the membranes of the trans-Golgi network (TGN) which
      leaves p37 soluble in the cytoplasm. We conclude that the palmitate moiety is
      necessary for targeting or anchoring p37 to the TGN membrane, where, along with
      other vaccinia virus-encoded proteins, p37 is involved in the complex process of
      virion envelopment and release.

PMID- 9573283
TI  - Human immunodeficiency virus inhibits multilineage hematopoiesis in vivo.
AB  - Human immunodeficiency virus type 1 (HIV-1)-infected individuals often exhibit
      multiple hematopoietic abnormalities reaching far beyond loss of CD4(+)
      lymphocytes. We used the SCID-hu (Thy/Liv) mouse (severe combined immunodeficient
      mouse transplanted with human fetal thymus and liver tissues), which provides an
      in vivo system whereby human pluripotent hematopoietic progenitor cells can be
      maintained and undergo T-lymphoid differentiation and wherein HIV-1 infection
      causes severe depletion of CD4-bearing human thymocytes. Herein we show that HIV
      1 infection rapidly and severely decreases the ex vivo recovery of human
      progenitor cells capable of differentiation into both erythroid and myeloid
      lineages. However, the total CD34+ cell population is not depleted. Combination
      antiretroviral therapy administered well after loss of multilineage progenitor
      activity reverses this inhibitory effect, establishing a causal role of viral
      replication. Taken together, our results suggest that pluripotent stem cells are
      not killed by HIV-1; rather, a later stage important in both myeloid and
      erythroid differentiation is affected. In addition, a primary virus isolated from
      a patient exhibiting multiple hematopoietic abnormalities preferentially depleted
      myeloid and erythroid colony-forming activity rather than CD4-bearing thymocytes
      in this system. Thus, HIV-1 infection perturbs multiple hematopoietic lineages in
      vivo, which may explain the many hematopoietic defects found in infected
      patients.

PMID- 9573284
TI  - Role of Rta in the translation of bicistronic BZLF1 of Epstein-Barr virus.
AB  - The BZLF1 gene of Epstein-Barr virus (EBV), which encodes a transcription factor,
      Zta, is transcribed into monocistronic and bicistronic mRNAs from two different
      promoters during the immediate-early stage of the EBV lytic cycle. It is
      generally accepted that the Zta protein translated from the monocistronic mRNA
      profoundly influences the activation of the EBV lytic cycle. In this study, we
      constructed a plasmid, pCMV-RZLUC, which can transcribe a bicistronic mRNA
      consisting of BRLF1 and a BZLF1-luc fusion gene under latent conditions. P3HR1
      cells transfected with this plasmid produce a luciferase activity which is
      approximately 17-fold higher than the activity exhibited by pRZLUC, a plasmid
      incapable of transcribing the bicistronic mRNA. Genetic analyses indicated that
      mutations in BRLF1 not only can decrease the translation of the fusion gene from
      the bicistronic mRNA but can also be complemented by a functional BRLF1 gene in
      cis. This observation implies that the product of BRLF1, Rta, is involved in the
      translation of the downstream gene. Results presented herein also demonstrate
      that these mutations cannot be complemented in trans with a plasmid
      overexpressing Rta, suggesting that the amount of Rta in the vicinity of the
      intercistronic region may be crucial for the translation. Furthermore, our
      results correspond to those of previous investigations indicating that the Zta
      protein can be translated from the bicistronic mRNA and that, similar to the
      translation of bicistronic ZLUC, mutations in BRLF1 also hinder the translation
      of Zta from the BRLF1-BZLF1 bicistronic mRNA. Translation of Zta from the
      bicistronic mRNA may play an essential role in the activation of the EBV lytic
      cycle.

PMID- 9573285
TI  - Immunoglobulin G, plasma cells, and lymphocytes in the murine vagina after
      vaginal or parenteral immunization with attenuated herpes simplex virus type 2.
AB  - This investigation evaluated immunity to vaginal herpes simplex virus type 2 (HSV
      2) infection after local or parenteral immunization with attenuated HSV-2.
      Vaginal immunization induced sterilizing immunity against challenge with a high
      dose of wild-type virus, whereas parenteral immunizations protected against
      neurologic disease but did not entirely prevent infection of the vagina. Vaginal
      immunization caused 86- and 31-fold increases in the numbers of immunoglobulin G
      (IgG) plasma cells in the vagina at 6 weeks and 10 months after immunization,
      whereas parenteral immunizations did not increase plasma cell numbers in the
      vagina. Vaginal secretion/serum titer ratios and specific antibody activities in
      vaginal secretions and serum indicated that IgG viral antibody was produced in
      the vagina and released into vaginal secretions at 6 weeks and 10 months after
      vaginal immunization but not after parenteral immunizations. In contrast to the
      case for plasma cells, the numbers of T and B lymphocytes in the vagina were
      similar in vaginally and parenterally immunized mice. Also, lymphocyte numbers in
      the vagina were markedly but similarly increased by vaginal challenge with HSV-2
      in both vaginally and parenterally immunized mice. Lymphocyte recruitment to the
      vagina after virus challenge appeared to involve memory lymphocytes, because it
      was not observed in nonimmunized mice. Thus, local vaginal immunization with
      attenuated HSV-2 increased the number of IgG plasma cells in the vagina and
      increased vaginal secretion/serum titer ratios to 3.0- to 4.7-fold higher than in
      parenterally immunized groups but caused little if any selective homing of T and
      B lymphocytes to the vagina.

PMID- 9573286
TI  - Alphavirus-specific cytotoxic T lymphocytes recognize a cross-reactive epitope
      from the capsid protein and can eliminate virus from persistently infected
      macrophages.
AB  - Persistent alphavirus infections in synovial and neural tissues are believed to
      be associated with chronic arthritis and encephalitis, respectively, and
      represent likely targets for CD8+ alphabeta cytotoxic T lymphocytes (CTL). Here
      we show that the capsid protein is a dominant target for alphavirus-specific CTL
      in BALB/c mice and that capsid-specific CTL from these mice recognize an H-2Kd
      restricted epitope, QYSGGRFTI. This epitope lies in the highly conserved region
      of the capsid protein, and QYSGGRFTI-specific CTL were cross reactive across a
      range of Old World alphaviruses. In vivo the acute primary viraemia of these
      highly cytopathic viruses was unaffected by QYSGGRFTI-specific CTL. However, in
      vitro these CTL were able to completely clear virus from macrophages persistently
      and productively infected with the arthrogenic alphavirus Ross River virus.

PMID- 9573287
TI  - Genotypic changes in human immunodeficiency virus type 1 associated with loss of
      suppression of plasma viral RNA levels in subjects treated with ritonavir
      (Norvir) monotherapy.
AB  - Ten subjects received 600 to 1,200 mg of the human immunodeficiency virus type 1
      (HIV-1) protease inhibitor ritonavir per day. Following 2 weeks of therapy,
      plasma HIV RNA levels decreased by a mean of 1. 57 (range, 0.89 to 1.96) log
      units. With continued therapy, HIV RNA levels began to rise in eight subjects.
      The initial rise in plasma RNA levels was temporally associated with the
      development and quantitative increase in the V82 resistance mutation. Doubling
      times of the V82A mutant virus were estimated to be 2.4 to 4.8 days. An L63P/A
      mutation was commonly present at baseline even in subjects with a durable
      virologic response. The concomitant acquisition of an L63P/A mutation with the
      V82A/F mutation at the time when plasma RNA levels rebounded suggests a role for
      the L63P/A mutation in improving the fitness of the V82A/F mutation. Subsequent
      additional genotypic changes at codons 54 and 84 were often associated with
      further increases in plasma RNA levels. Ongoing viral replication in the presence
      of drugs resulted in the appearance of additional genotypic changes, including
      the L90M saquinavir resistance mutation, and decreased phenotypic susceptibility.
      The relative fitness of the protease V82A ritonavir resistance mutation and
      reverse transcriptase T215Y/F zidovudine resistance mutation following drug
      withdrawal were estimated to be 96 to 98% that of the wild type. Durability of
      the virologic response was associated with plasma RNA levels at the nadir. A
      virologic response beyond 60 days was not observed unless plasma HIV RNA levels
      were suppressed below 2,000 copies/ml, consistent with estimates from V82A
      doubling times for selection of a single resistance mutation to dominate the
      replicating population.

PMID- 9573288
TI  - Complete genomic sequence of border disease virus, a pestivirus from sheep.
AB  - The genus Pestivirus of the family Flaviviridae comprises three established
      species, namely, bovine viral diarrhea virus (BVDV), classical swine fever virus
      (CSFV), and border disease virus from sheep (BDV). In this study, we report the
      first complete nucleotide sequence of BDV, that of strain X818. The genome is
      12,333 nucleotides long and contains one long open reading frame encoding 3, 895
      amino acids. The 5' noncoding region (NCR) of BDV X818 consists of 372
      nucleotides and is thus similar in length to the 5' NCR reported for other
      pestiviruses. The 3' NCR of X818 is 273 nucleotides long and thereby at least 32
      nucleotides longer than the 3' NCR of pestiviruses analyzed thus far. Within the
      3' NCR of BDV X818, the sequence motif TATTTATTTA was identified at four
      locations. The same repeat was found at two or three locations within the 3' NCR
      of different CSFV isolates but was absent in the 3' NCR of BVDV. Analysis of five
      additional BDV strains showed that the 3' NCR sequences are highly conserved
      within this species. Comparison of the deduced amino acid sequence of X818 with
      the ones of other pestiviruses allowed the prediction of polyprotein cleavage
      sites which were conserved with regard to the structural proteins. It has been
      reported for two BVDV strains that cleavage at the nonstructural (NS) protein
      sites 3/4A, 4A/4B, 4B/5A, and 5A/5B is mediated by the NS3 serine protease and
      for each site a conserved leucine was found at the P1 position followed by either
      serine or alanine at P1' (N. Tautz, K. Elbers, D. Stoll, G. Meyers, and H.-J.
      Thiel, J. Virol. 71:5415-5422, 1997; J. Xu, E. Mendez, P. R. Caron, C. Lin, M. A.
      Murcko, M. S. Collett, and C. M. Rice, J. Virol. 71:5312-5322). Interestingly,
      P1' of the predicted NS5A/5B cleavage site of BDV is represented by an asparagine
      residue. Transient expression studies demonstrated that this unusual NS5A/5B
      processing site is efficiently cleaved by the NS3 serine protease of BDV.

PMID- 9573289
TI  - DNA immunization with minigenes: low frequency of memory cytotoxic T lymphocytes
      and inefficient antiviral protection are rectified by ubiquitination.
AB  - Our previous studies have shown that isolated cytotoxic T lymphocyte (CTL), B
      cell, and T-helper epitopes, for which we coined the term minigenes, can be
      effective vaccines; when expressed from recombinant vaccinia viruses, these short
      immunogenic sequences confer protection against a variety of viruses and
      bacteria. In addition, we have previously demonstrated the utility of DNA
      immunization using plasmids encoding full-length viral proteins. Here we combine
      the two approaches and evaluate the effectiveness of minigenes in DNA
      immunization. We find that DNA immunization with isolated minigenes primes virus
      specific memory CTL responses which, 4 days following virus challenge, appear
      similar in magnitude to those induced by vaccines known to be protective.
      Surprisingly, this vigorous CTL response fails to confer protection against a
      normally lethal virus challenge, although the CTL appear fully functional
      because, along with their high lytic activity, they are similar in affinity and
      cytokine secretion to CTL induced by virus infection. However this DNA
      immunization with isolated minigenes results in a low CTL precursor frequency;
      only 1 in approximately 40,000 T cells is epitope specific. In contrast, a
      plasmid encoding the same minigene sequences covalently attached to the cellular
      protein ubiquitin induces protective immunity and a sixfold-higher frequency of
      CTL precursors. Thus, we show that the most commonly employed criterion to
      evaluate CTL responses-the presence of lytic activity following secondary
      stimulation-does not invariably correlate with protection; instead, the better
      correlate of protection is the CTL precursor frequency. Recent observations
      indicate that certain effector functions are active in memory CTL and do not
      require prolonged stimulation. We suggest that these early effector functions of
      CTL, immediately following infection, are critical in controlling virus
      dissemination and in determining the outcome of the infection. Finally, we show
      that improved performance of the ubiquitinated minigenes most probably requires
      polyubiquitination of the fusion protein, suggesting that the enhancement results
      from more effective delivery of the minigene to the proteasome.

PMID- 9573290
TI  - Limited transmission of Kaposi's sarcoma-associated herpesvirus in cultured
      cells.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus 8)
      is a novel gammaherpesvirus strongly implicated in the pathogenesis of Kaposi's
      sarcoma. Although virions can be produced in high yield from latently infected B
      cell lines treated with phorbol esters, little is known about the infectivity of
      such virus, and efficient serial propagation of KSHV has been problematic. Here
      we report on the infectivity of KSHV produced from phorbol-induced BCBL-1 cells,
      employing an assay based on the detection of a spliced late mRNA by a sensitive
      reverse transcriptase PCR (RT-PCR) method. The results of this study confirm
      previous observations that 293 cells are susceptible to viral infection; however,
      infection with BCBL-1-derived virus is inefficient and the pattern of viral gene
      expression in infected cells may not fully reproduce that of authentic lytic
      infection. In keeping with this finding, serial propagation of BCBL-1-derived
      virus could not be demonstrated on 293 cells. Eleven of 38 other cell lines
      tested also supported KSHV infection, as judged by this RT-PCR assay, including
      cells of B-cell, endothelial, epithelial, and fibroblastic origin; however, in
      all cases, infection proceeded at or below the levels observed in 293 cells.

PMID- 9573292
TI  - Relative rates of retroviral reverse transcriptase template switching during RNA-
      and DNA-dependent DNA synthesis.
AB  - Retroviral reverse transcriptases (RTs) frequently switch templates during DNA
      synthesis, which can result in mutations and recombination. The relative rates of
      in vivo RT template switching during RNA- and DNA-dependent DNA synthesis are
      unknown. To determine the relative rates of RT template switching during copying
      of RNA and DNA templates, we constructed spleen necrosis virus-based retroviral
      vectors containing a 400-bp direct repeat. The directly repeated sequences were
      upstream of the polypurine tract (PPT) in the RB-LLP vector; the same direct
      repeats flanked the PPT and attachment site (att) in the RB-LPL vector. RT
      template switching events could occur during either RNA- or DNA-dependent DNA
      synthesis and delete one copy of the direct repeat plus the intervening
      sequences. RB-LLP vectors that underwent direct repeat deletions during RNA- and
      DNA-dependent DNA synthesis generated viral DNA that could integrate into the
      host genome. However, any deletion of the direct repeats in the RB-LPL vector
      that occurred during RNA-dependent DNA synthesis resulted in deletion of the
      essential PPT and att site and generated a dead-end viral DNA product. Thus, only
      RB-LPL vectors that underwent direct repeat deletions during DNA-dependent DNA
      synthesis could integrate to form proviruses. The RB-LLP and RB-LPL vectors were
      permitted to undergo a single replication cycle, and the frequencies of direct
      repeat deletions were determined by PCR and Southern analysis of the resulting
      proviruses. A comparison of the frequency of direct repeat deletions in the RB
      LLP and RB-LPL vectors indicated that the in vivo rates of RT template switching
      during RNA- and DNA-dependent DNA synthesis are nearly identical.

PMID- 9573291
TI  - Functional interaction of human immunodeficiency virus type 1 Vpu and Gag with a
      novel member of the tetratricopeptide repeat protein family.
AB  - Viral protein U (Vpu) is a protein encoded by human immunodeficiency virus type 1
      (HIV-1) that promotes the degradation of the virus receptor, CD4, and enhances
      the release of virus particles from cells. We isolated a cDNA that encodes a
      novel cellular protein that interacts with Vpu in vitro, in vivo, and in yeast
      cells. This Vpu-binding protein (UBP) has a molecular mass of 41 kDa and is
      expressed ubiquitously in human tissues at the RNA level. UBP is a novel member
      of the tetratricopeptide repeat (TPR) protein family containing four copies of
      the 34-amino-acid TPR motif. Other proteins that contain TPR motifs include
      members of the immunophilin superfamily, organelle-targeting proteins, and a
      protein phosphatase. UBP also interacts directly with HIV-1 Gag protein, the
      principal structural component of the viral capsid. However, when Vpu and Gag are
      coexpressed, stable interaction between UBP and Gag is diminished. Furthermore,
      overexpression of UBP in virus-producing cells resulted in a significant
      reduction in HIV-1 virion release. Taken together, these data indicate that UBP
      plays a role in Vpu-mediated enhancement of particle release.

PMID- 9573293
TI  - Simian-human immunodeficiency virus (SHIV) containing the nef/long terminal
      repeat region of the highly virulent SIVsmmPBj14 causes PBj-like activation of
      cultured resting peripheral blood mononuclear cells, but the chimera showed No
      increase in virulence.
AB  - SIVsmmPBj14 is a highly pathogenic lentivirus which causes acute diarrhea, rash,
      massive lymphocyte proliferation predominantly in the gastrointestinal tract, and
      death within 7 to 14 days. In cell culture, the virus has mitogenic effects on
      resting macaque T lymphocytes. In contrast, SIVmac239 causes AIDS in rhesus
      macaques, generally within 2 years after inoculation. In a previous study,
      replacement of amino acid residues 17 and 18 of the Nef protein of SIVmac239 with
      the corresponding amino acid residues of the Nef protein of SIVsmmPBj14 yielded a
      PBj-like virus that caused extensive activation of resting T lymphocytes in
      cultures and acute PBj-like disease when inoculated into pig-tailed macaques.
      This study suggested that nef played a major role in both processes. In this
      study, we replaced the nef/long terminal repeat (LTR) region of a nonpathogenic
      simian-human immunodeficiency virus (SHIV), SHIVPPc, with the corresponding
      region from SIVsmmPBj14 and examined the biological properties of the resultant
      virus. Like SIVsmmPBj14, SHIVPPcPBjnef caused massive stimulation of resting
      peripheral blood mononuclear cells (PBMC), which then produced virus in the
      absence of extraneous interleukin 2. However, when inoculated into macaques, the
      virus failed to replicate productively or cause disease. Thus, while these
      results confirmed that the nef/LTR region of SIVsmmPBj14 played a major role in
      the activation of resting PBMC, duplication of the cellular activation process in
      macaques may require a further interaction between nef and the envelope
      glycoprotein of simian immunodeficiency virus because SHIV, containing the
      envelope of human immunodeficiency virus type 1, failed to cause activation in
      vivo.

PMID- 9573294
TI  - The major structural protein of African swine fever virus, p73, is packaged into
      large structures, indicative of viral capsid or matrix precursors, on the
      endoplasmic reticulum.
AB  - African swine fever virus (ASFV) is a large enveloped DNA virus that shares the
      striking icosahedral symmetry of iridoviruses. To understand the mechanism of
      assembly of ASFV, we have been studying the biosynthesis and subcellular
      distribution of p73, the major structural protein of ASFV. Sucrose density
      sedimentation of lysates prepared from infected cells showed that newly
      synthesized p73 was incorporated into a complex with a size of 150 to 250 kDa.
      p73 synthesized by in vitro translation migrated at 70 kDa, suggesting that
      cellular and/or viral proteins are required for the formation of the 150- to 250
      kDa complex. During a 2-h chase, approximately 50% of the newly synthesized pool
      of p73 bound to the endoplasmic reticulum (ER). During this period, the membrane
      bound pool of p73, but not the cytosolic pool, formed large complexes of
      approximately 50,000 kDa. The complexes were formed via assembly intermediates,
      and the entire membrane-associated pool of p73 was incorporated into the 50,000
      kDa complex within 2 h. The 50,000-kDa complexes containing p73 were also
      detected in virions secreted from cells. Immunoprecipitation of sucrose gradients
      with sera taken from hyperimmune pigs suggested that p73 was the major component
      of the 50,000-kDa complex. It is possible, therefore, that the complex contains
      between 600 and 700 copies of p73. The kinetics of complex formation and
      envelopment of p73 were similar, and complex formation and envelopment were both
      reversibly inhibited by cycloheximide, suggesting a functional link between
      complex assembly and ASFV envelopment. A protease protection assay detected
      50,000-kDa complexes on the inside and outside of the membranes forming the viral
      envelope. The identification of a complex containing p73 beneath the envelope of
      ASFV suggests that p73 may be a component of the inner core shell or matrix of
      ASFV. The outer pool may represent p73 within the outer capsid layer of the
      virus. In summary, the data suggest that the assembly of the inner core matrix
      and outer capsid of ASFV takes place on the ER membrane during envelopment and
      that these structures are not preassembled in the cytosol.

PMID- 9573295
TI  - Recombinant human parvovirus B19 vectors: erythroid cell-specific delivery and
      expression of transduced genes.
AB  - A novel packaging strategy combining the salient features of two human
      parvoviruses, namely the pathogenic parvovirus B19 and the nonpathogenic adeno
      associated virus type 2 (AAV), was developed to achieve erythroid cell-specific
      delivery as well as expression of the transduced gene. The development of such a
      chimeric vector system was accomplished by packaging heterologous DNA sequences
      cloned within the inverted terminal repeats of AAV and subsequently packaging the
      DNA inside the capsid structure of B19 virus. Recombinant B19 virus particles
      were assembled, as evidenced by electron microscopy as well as DNA slot blot
      analyses. The hybrid vector failed to transduce nonerythroid human cells, such as
      293 cells, as expected. However, MB-02 cells, a human megakaryocytic leukemia
      cell line which can be infected by B19 virus following erythroid differentiation
      with erythropoietin (N. C. Munshi, S. Z. Zhou, M. J. Woody, D. A. Morgan, and A.
      Srivastava, J. Virol. 67:562-566, 1993) but lacks the putative receptor for AAV
      (S. Ponnazhagan, X.-S. Wang, M. J. Woody, F. Luo, L. Y. Kang, M. L. Nallari, N.
      C. Munshi, S. Z. Zhou, and A. Srivastava, J. Gen. Virol. 77:1111-1122, 1996),
      were readily transduced by this vector. The hybrid vector was also found to
      specifically target the erythroid population in primary human bone marrow cells
      as well as more immature hematopoietic progenitor cells following erythroid
      differentiation, as evidenced by selective expression of the transduced gene in
      these target cells. Preincubation with anticapsid antibodies against B19 virus,
      but not anticapsid antibodies against AAV, inhibited transduction of primary
      human erythroid cells. The efficiency of transduction of primary human erythroid
      cells by the recombinant B19 virus vector was significantly higher than that by
      the recombinant AAV vector. Further development of the AAV-B19 virus hybrid
      vector system should prove beneficial in gene therapy protocols aimed at the
      correction of inherited and acquired human diseases affecting cells of erythroid
      lineage.

PMID- 9573296
TI  - Similar levels of human immunodeficiency virus type 1 replication in human TH1
      and TH2 clones.
AB  - Studies on the development and function of CD4+ TH1 and TH2 cells during the
      progression to AIDS may increase the understanding of AIDS pathogenesis. The
      preferential replication of human immunodeficiency virus (HIV) in either TH1 or
      TH2 cells could alter the delicate balance of the immune response. TH1 (gamma
      interferon [IFN-gamma] positive, interleukin-4 [IL-4] and IL-5 negative) and TH2
      (IFN-gamma negative, IL-4 and IL-5 positive) clones, developed from several
      healthy donors, pedigreed by reverse transcriptase PCR (RT-PCR) and enzyme linked
      immunosorbent assay have similar levels of cell surface expression of CD4 and
      several chemokine receptor cofactors necessary for viral entry. After activation
      by specific antigens and infection with T-cell-tropic strains of HIV type 1 (HIV
      1), TH1 and TH2 clones showed similar levels of viral entry and reverse
      transcription. At days 3 through 14 postinfection, HIV replicated to similar
      levels in several TH1 and TH2 clones as measured by release of HIV p24 and total
      number of copies of gag RNA/total cell RNA as measured by RT-PCR. When values
      were normalized for viable cell number in three clones of each type, there was up
      to twofold more HIV RNA in TH1 than TH2 cells. In addition, several primary
      monocytotropic HIV-1 strains were able to replicate to similar levels in TH1 and
      TH2 cells. These studies suggest that the importance of TH1 and TH2 subsets in
      AIDS pathogenesis transcends clonal differences in their ability to support HIV
      replication.

PMID- 9573297
TI  - Rabbit genital tissue is susceptible to infection by rabbit oral papillomavirus:
      an animal model for a genital tissue-targeting papillomavirus.
AB  - Rabbit oral papillomavirus (ROPV) is a mucosatropic papillomavirus which
      naturally infects oral mucosal sites of domestic rabbits. In this study, we
      tested the hypothesis that rabbit genital mucosa is also susceptible to ROPV
      infection by using the athymic mouse xenograft system and adult immunocompetent
      rabbits. Subrenal xenografts of ROPV-infected rabbit vulvar and penile sheath
      tissues were strongly positive for ROPV infection by histologic, in situ
      hybridization, and Southern analyses. Direct inoculation of adult rabbit penises
      with infectious ROPV produced small raised lesions of approximately 1 by 1 by 1
      mm that were ROPV positive by both in situ hybridization and Southern analyses
      and were also viral capsid antigen positive by immunohistological staining.
      Infection of rabbit genital tissues with ROPV may be a useful animal model for
      the study of genital tissue-targeting papillomaviruses.

PMID- 9573298
TI  - Measles virus infection and replication in undifferentiated and differentiated
      human neuronal cells in culture.
AB  - Measles virus (MV) infection of the human central nervous system (CNS) typically
      involves widespread infection of neurons. However, little is known about how they
      become infected, how defective virus arises and accumulates, or how virus spreads
      among the cells of the CNS. In vitro studies of viral interactions with human
      neuronal cells may contribute to the resolution of such issues. In mixed cultures
      containing differentiated human neuronal (hNT2) cells and neuroepithelial cells,
      immunofluorescence studies show that the neurons, unlike both their NT2
      progenitors and the neuroepithelial cells, are not initially susceptible to MV
      infection. This is possibly due to their lack of expression of CD46, a known cell
      surface receptor for MV. Later in the course of infection, however, both MV
      proteins and genomic RNA become detectable in their processes, where they contact
      infected, fully permissive neuroepithelial cells. Such a mechanism of virus
      transfer may be involved in the initiation and spread of persistent MV infection
      in diseases such as subacute sclerosing panencephalitis. Furthermore, mutated
      defective virus may readily accumulate and spread without the need, at any stage,
      for viral maturation and budding.

PMID- 9573299
TI  - Actin-dependent receptor colocalization required for human immunodeficiency virus
      entry into host cells.
AB  - Human immunodeficiency virus (HIV) envelope binds CD4 and a chemokine receptor in
      sequence, releasing hydrophobic viral gp41 residues into the target membrane. HIV
      entry required actin-dependent concentration of coreceptors, which could be
      disrupted by cytochalasin D (CytoD) without an effect on cell viability or
      mitosis. Pretreatment of peripheral blood mononuclear cells, but not virus,
      inhibited entry and infection. Immunofluorescent confocal microscopy of activated
      cells revealed CD4 and CXCR4 in nonoverlapping patterns. Addition of gp120 caused
      polarized cocapping of both molecules with subsequent pseudopod formation, while
      CytoD pretreatment blocked these membrane changes completely.

PMID- 9573300
TI  - Isolation and propagation of human papillomavirus type 16 in human xenografts
      implanted in the severe combined immunodeficiency mouse.
AB  - We report the isolation and propagation of human papillomavirus type 16, the main
      agent of cervical cancer, using human foreskin fragments implanted in severe
      combined immunodeficiency mice. The infection produced viral particles, and with
      each passage of the virus it caused lesions identical to intraepithelial
      neoplasia, the precursor to carcinoma.

PMID- 9573301
TI  - Nucleotide sequence of porcine circovirus associated with postweaning
      multisystemic wasting syndrome in pigs.
AB  - This article describes the nucleotide sequence of a porcine circovirus (PCV)
      which possesses a high degree of association with postweaning multisystemic
      wasting syndrome (PMWS), a newly described disease of young pigs. The DNA
      sequence of this PMWS-associated PCV (pmws PCV) has 68% homology with that of a
      previously published nonpathogenic strain of PCV. The strains appear to be
      closely related yet distinct from one another.

PMID- 9573302
TI  - Recombination of engineered defective RNA species produces infective potyvirus in
      planta.
AB  - Recombination occurred between viral genomes when squash plants were cobombarded
      with mixtures of engineered disabled constructs of a zucchini yellow mosaic
      potyvirus. Single and double recombinants were detected in the progeny. Genes
      involved in the recombination process and the mechanisms of recombination were
      studied in potyviruses for the first time.

PMID- 9573303
TI  - Human immunodeficiency virus type 2 Vpx-Gag interaction.
AB  - Incorporation of Vpx into human immunodeficiency virus type 2 (HIV-2) virus-like
      particles is mediated by the Gag polyprotein. We have identified residues 15 to
      40 of Gag p6 and residues 73 to 89 of Vpx as being necessary for virion
      incorporation. In addition, we show enhanced in vitro binding of Vpx to a
      chimeric HIV-1/HIV-2 Gag construct containing residues 2 to 49 of HIV-2 p6 and
      demonstrate that the presence of residues 73 to 89 of Vpx allows for in vitro
      binding to HIV-2 Gag.

PMID- 9573304
TI  - Polarized budding of measles virus is not determined by viral surface
      glycoproteins.
AB  - For viruses that mature by a budding process, the envelope glycoproteins are
      considered the major determinants for the site of virus release from polarized
      epithelial cells. Viruses are usually released from that membrane domain where
      the viral surface glycoproteins are transported to. We here report that measles
      virus has developed a different maturation strategy. Measles virus was found to
      be released from the apical membrane domain of polarized epithelial cells, though
      the surface glycoproteins H and F were transported in a nonpolarized fashion and
      to the basolateral membrane domain, respectively.

PMID- 9573305
TI  - Cloning and expression of a human T-lymphotropic virus type 1 protein with
      reverse transcriptase activity.
AB  - Unlike most other characterized retroviruses, there is little published
      information on the biochemical properties of human T-lymphotropic virus type 1
      (HTLV-1) reverse transcriptase (RT). Specifically, no reports of a cloned
      functional RT enzyme have been published. Since the RT enzyme is an essential
      component of the virus, our objective was to clone, express, and purify a
      functional RT enzyme from HTLV-1. Our approach was to clone and express a protein
      of approximately 60 to 65 kDa that we hypothesized would correspond to the RT
      region encoded by the pol reading frame. The predicted region encoding the RT
      enzyme comprised nucleotides 2617 to 4312 of the HTLV-1 MT-2 isolate. A putative
      RT gene was obtained by PCR and was ligated into various prokaryotic expression
      vectors. A novel cloning approach allowed us to generate a stable clone in the
      prokaryotic expression vector pGEX-4T-1 and produce a recombinant protein of
      approximately 60 to 65 kDa. The partially purified protein displays RT activity
      in both amplification RT (AMP-RT) assays and traditional RT assays. This is the
      first report of a cloned protein from HTLV-1 which displays RT activity and is
      the first step in the characterization of HTLV-1 RT.

PMID- 9573306
TI  - CD28-B7 costimulatory blockade by CTLA4Ig delays the development of retrovirus
      induced murine AIDS.
AB  - Mouse AIDS (MAIDS) induced in C57BL/6 mice by infection with a replication
      defective retrovirus (Du5H) combines extensive lymphoproliferation and profound
      immunodeficiency. Although B cells are the main target of viral infection, recent
      research has focused on CD4(+) T cells, the activation of which is a key event in
      MAIDS induction and progression. A preliminary observation of increased
      expression of B7 molecules on B cells in MAIDS prompted us to address the
      possible involvement of the CD28/B7 costimulatory pathway in MAIDS. Mice infected
      with the MAIDS-inducing viral preparation were treated with murine fusion protein
      CTLA4Ig (3 x 50 microg/week given intraperitoneally), a competitive inhibitor of
      physiological CD28-B7 interactions. In CTLA4Ig-treated animals, the onset of the
      disease was delayed, lymphoproliferation progressed at a much slower rate than in
      untreated mice, and the loss of in vitro responsiveness to mitogens was reduced.
      Relative expression of Du5H did not differ between treated and untreated animals.
      These results suggest that the CD28/B7 costimulatory pathway contributes to MAIDS
      development.

PMID- 9573307
TI  - Altered plaque formation by recombinant vaccinia virus expressing simian
      immunodeficiency virus Nef.
AB  - The nef gene of primate lentiviruses encodes a myristoylated protein that is
      important for pathogenicity and the maintenance of high virus loads. A deletion
      in nef leads to a significant reduction of the pathogenicity of simian
      immunodeficiency virus (SIV) in macaques. At the cellular and biochemical levels,
      Nef has been shown to down-regulate CD4 and major histocompatibility complex
      class I molecules and to interact with cellular protein kinases. The importance
      of these activities for Nef function remains uncertain. We have prepared vaccinia
      virus recombinants expressing different alleles of SIV nef. When grown on TK- 143
      cells, recombinants constructed with the nef allele from SIVmac1A11 produced
      typical plaques while recombinants expressing the nef allele from SIVmac239-R1
      gave rise to plaques with altered morphology. By using chimeric Nef proteins and
      site-directed mutagenesis, the amino acid responsible for altered plaque
      formation was mapped to a leucine at residue 211. In vitro phosphorylation of
      immunoprecipitates prepared from cells infected with the vaccinia virus
      recombinants resulted in labeled proteins of 62 and 90 kDa. The recombinants
      differed in the ability to stimulate phosphorylation, and the leucine at residue
      211 was again found to be the determining amino acid. These results might help
      elucidate the role of nef in the pathogenesis of SIV.

PMID- 9573308
TI  - Pseudotype formation of Moloney murine leukemia virus with Sendai virus
      glycoprotein F.
AB  - Mixed infection of cells with both Moloney murine leukemia virus (MoMLV) and
      related or heterologous viruses produces progeny pseudotype virions bearing the
      MoMLV genome encapsulated by the envelope of the other virus. In this study,
      pseudotype formation between MoMLV and the prototype parainfluenza virus Sendai
      virus (SV) was investigated. We report for the first time that SV infection of
      MoMLV producer cells results in the formation of MoMLV(SV) pseudotypes, which
      display a largely extended host range compared to that of MoMLV particles. This
      could be associated with SV hemagglutinin-neuraminidase (SV-HN) glycoprotein
      incorporation into MoMLV envelopes. In contrast, solitary incorporation of the
      other SV glycoprotein, SV fusion protein (SV-F), resulted in a distinct and
      narrow extension of the MoMLV host range to asialoglycoprotein receptor (ASGP-R)
      positive cells (e.g., cultured human hepatoma cells). Since stably ASGP-R cDNA
      transfected MDCK cells, but not parental ASGP-R-negative MDCK cells, were found
      to be transduced by MoMLV(SV-F) pseudotypes and transduction of ASGP-R-expressing
      cells was found to be inhibited by ASGP-R antiserum, a direct proof for the ASGP
      R-restricted tropism of MoMLV(SV-F) pseudotypes was provided. Cultivation of ASGP
      R-positive HepG2 hepatoma cells on Transwell-COL membranes led to a significant
      enhancement of MoMLV(SV-F) titers in subsequent flowthrough transduction
      experiments, thereby suggesting the importance of ASGP-R accessibility at the
      basolateral domain for MoMLV(SV-F) pseudotype transduction. The availability of
      such ASGP-R-restricted MoMLV(SV-F)-pseudotyped vectors opens up new perspectives
      for future liver-restricted therapeutic gene transfer applications.

PMID- 9573309
TI  - Human immunodeficiency virus type 1 protease genotypes and in vitro protease
      inhibitor susceptibilities of isolates from individuals who were switched to
      other protease inhibitors after long-term saquinavir treatment.
AB  - An understanding of the mechanisms of virologic cross-resistance between human
      immunodeficiency virus type 1 protease inhibitors is important for the
      establishment of effective treatment strategies for patients who no longer
      respond to their initial protease inhibitor. Protease gene sequencing results
      from patients treated with saquinavir showed significant increases in the
      frequency of the G48V protease mutation in patients receiving higher doses of the
      drug. In addition, all six patients who developed the G48V mutation during
      saquinavir therapy developed the V82A mutation either on continued saquinavir or
      after a switch to nelfinavir or indinavir. In vitro susceptibility assays showed
      that all 13 isolates with reduced susceptibilities to two or more protease
      inhibitors had either the G48V or L90M mutation, along with an average of six
      other protease mutations. Reduced susceptibility to nelfinavir was found in 14
      isolates, but only 1 possessed the D30N mutation. These results suggest that
      mutations selected in vivo by initial saquinavir therapy may provide more cross
      resistance to the other protease inhibitors than has been previously reported.

PMID- 9573310
TI  - The N-terminal extension of the influenza B virus nucleoprotein is not required
      for nuclear accumulation or the expression and replication of a model RNA.
AB  - The nucleoprotein (NP) of influenza B virus is 50 amino acids longer at the N
      terminus than influenza A virus NP and lacks homology to the A virus protein over
      the first 69 residues. We have deleted the N-terminal 51 and 69 residues of the
      influenza B/Ann Arbor/1/66 virus NP and show that nuclear accumulation of the
      protein is unaffected. This indicates that the nuclear localization signal is not
      located at the extreme N terminus, as in influenza A virus NP. To determine if
      the N-terminal mutants could support the expression and replication of a model
      influenza B virus RNA, the genes encoding the subunits of the viral RNA-dependent
      RNA polymerase (PA, PB1, and PB2) were cloned. Coexpression of NP and the P
      proteins in 293 cells was found to permit the expression and replication of a
      transfected model RNA based on segment 4 of B/Maryland/59, in which the
      hemagglutinin-coding region was replaced by a chloramphenicol acetyltransferase
      gene. The expression and replication of the synthetic RNA were not affected by
      the replacement of NP with NP mutants lacking the N-terminal 51 or 69 residues,
      indicating that the N-terminal extension is not required for transcription or
      replication of the viral RNA. In addition, we report that the influenza B virus
      NP cannot be functionally replaced by type A virus NP in this system.

PMID- 9573311
TI  - Incorporation of fowl plague virus hemagglutinin into murine leukemia virus
      particles and analysis of the infectivity of the pseudotyped retroviruses.
AB  - We describe retrovirus particles carrying the fowl plague virus (FPV)
      hemagglutinin (HA). When expressed in cells providing Moloney murine leukemia
      virus (MoMLV) Gag and Pol proteins and a lacZ retroviral vector, FPV HA was found
      to be efficiently expressed, correctly processed, and stably incorporated into
      retroviral particles. HA-bearing retroviruses were infectious with a wide host
      range and were only 10-fold less infectious than retroviruses carrying wild-type
      MLV retroviral envelopes. We also coexpressed HA proteins in retroviral particles
      with chimeric MoMLV-derived envelope glycoproteins that efficiently retarget
      virus attachment but are only weakly fusogenic. Our results suggest that HA can
      in some cases enhance the fusion ability of these retroviral particles, depending
      on the cell surface molecule that is used as a receptor.

PMID- 9573312
TI  - A recombinant classical swine fever virus stably expresses a marker gene.
AB  - The gene coding for bacterial chloramphenicol acetyltransferase (CAT) was
      inserted in frame into the viral Npro gene of the full-length cDNA clone pA187-1
      of the classical swine fever virus (CSFV) strain Alfort/187. RNA transcribed in
      vitro from the resulting plasmid was transfected into SK-6 porcine kidney cells.
      Infectious progeny virus vA187-CAT recovered from transfected cells had growth
      characteristics indistinguishable from those of parental virus vA187-1. In cells
      infected with vA187-CAT the predicted fusion protein, CAT-Npro, was detected, and
      it retained the enzymatic activities of both CAT and Npro. The CAT gene remained
      stably inserted in the viral genome after 10 virus passages. Thus, marker virus
      vA187-CAT represents a useful tool for quantitative analysis of viral replication
      and gene expression.

PMID- 9573313
TI  - Cleavage of rhesus rotavirus VP4 after arginine 247 is essential for rotavirus
      like particle-induced fusion from without.
AB  - We recently described our finding that recombinant baculovirus-produced virus
      like particles (VLPs) can induce cell-cell fusion similar to that induced by
      intact rotavirus in our assay for viral entry into tissue culture cells (J. M.
      Gilbert and H. B. Greenberg, J. Virol. 71:4555-4563, 1997). The conditions
      required for syncytium formation are similar to those for viral penetration of
      the plasma membrane during the course of viral infection. This VLP-mediated
      fusion activity was dependent on the presence of the outer-layer proteins, viral
      protein 4 (VP4) and VP7, and on the trypsinization of VP4. Fusion activity
      occurred only with cells that are permissive for rotavirus infection. Here we
      begin to dissect the role of VP4 in rotavirus entry by examining the importance
      of the precise trypsin cleavage of VP4 and the activation of VP4 function related
      to viral entry. We present evidence that the elimination of the three trypsin
      susceptible arginine residues of VP4 by specific site-directed mutagenesis
      prevents syncytium formation. Two of the three arginine residues in VP4 are
      dispensable for syncytium formation, and only the arginine residue at site 247
      appears to be required for activation of VP4 functions and cell-cell fusion.
      Using the recombinant VLPs in our syncytium assay will aid in understanding the
      conformational changes that occur in VP4 involved in rotavirus penetration into
      host cells.

PMID- 9573333
TI  - Do natural antisense transcripts make sense in eukaryotes?
AB  - The existence of naturally occurring antisense RNAs has been illustrated, in
      eukaryotes, by an increasing number of reports. The following review presents the
      major findings in this field, with a special focus on the regulation of gene
      expression exerted by endogenous complementary transcripts. A large variety of
      eukaryotic organisms, contains antisense transcripts. Moreover, the great
      diversity of genetic loci encoding overlapping sense and antisense RNAs suggests
      that such transcripts may be involved in numerous biological functions, such as
      control of development, adaptative response. viral infection. The regulation of
      gene expression by endogenous antisense RNAs seems of general importance in
      eukaryotes as already established in prokaryotes: it is likely to be involved in
      the control of various biological functions and to play a role in the development
      of pathological situations. Several experimental evidences for coupled, balanced
      or unbalanced expression of sense and antisense RNAs suggest that antisense
      transcripts may govern the expression of their sense counterparts. Furthermore,
      documented examples indicate that this control may be exerted at many levels of
      gene expression (transcription, maturation, transport, stability and
      translation). This review also addresses the underlying molecular mechanisms of
      antisense regulation and presents the current mechanistic hypotheses.

PMID- 9573334
TI  - Growth hormone and placental lactogen: biology, medicine and biotechnology.
AB  - Molecular cloning gave us access to the gene members of the human growth hormone
      and placental lactogen multigene family. Genomic sequencing provided clues for
      the understanding of the origin, functioning and regulation of this family. It
      has also allowed us to develop new diagnostic approaches for deficiencies of
      these hormones and to make new biotechnological contributions.

PMID- 9573335
TI  - The chicken CP49 gene contains an extra exon compared to the human CP49 gene
      which identifies an important step in the evolution of the eye lens intermediate
      filament proteins.
AB  - The gene structure for chicken CP49 gene is presented. It differs from the human
      CP49 gene with the presence of an extra exon in helix IB and the apparent loss of
      an intron, intron H. The CP49 gene localises to chromosome 2 in the chicken
      genome where it is flanked by homologues that map to human chromosome 10p13 (VIM)
      6p24-p23 (BMP6). Two transcripts, CP49 and CP49ins, are produced from the single
      chicken CP49 gene. The difference is a 49-amino-acid insertion in helix IB of
      CP49 that is encoded by a novel exon found in the chicken CP49 gene. An extended
      helix IB is believed to be a characteristic of the ancestral intermediate
      filament protein as it is found in many invertebrate intermediate filament
      proteins but has been lost from all vertebrate intermediate filament proteins
      except the nuclear lamins. Although the intron position and length of the helix
      IB insert sequences in CP49ins differ to those found both in the invertebrate
      intermediate filament proteins and the vertebrate lamins, the CP49 gene is the
      first vertebrate cytoplasmic intermediate filament protein to be described with
      an extended helix IB. The chicken CP49 gene is also the first where differential
      splicing can remove such a feature. Human and bovine CP49 appear to have lost the
      helix IB insert sequences, and so the avian CP49 gene provides an interesting
      evolutionary link between the eye lens proteins and the ancestral intermediate
      filament protein.

PMID- 9573336
TI  - Diverse modes of alternative splicing of human splicing factor SF1 deduced from
      the exon-intron structure of the gene.
AB  - Several cDNAs encoding the essential human splicing facor (SF) 1 have been
      cloned. Comparison of the cDNA sequences suggested that the corresponding mRNAs
      are generated by alternative splicing from a common pre-mRNA. To confirm this
      assumption and to analyze possible modes used in the generation of these mRNAs,
      we have determined the structure of the gene encoding SF1. The gene extends over
      approximately 15kb and contains 14 exons. The exon/intron structure and sequences
      at the splice sites are highly conserved in the corresponding mouse gene. The
      human SF1 gene is located on chromosome 11 close to the gene encoding Menin,
      recently identified as the gene responsible for multiple endocrine neoplasia-type
      1 (MEN1). The absence of a TATA box in the 5' flanking region of the SF1
      transcription unit suggests that the SF1 gene represents a housekeeping gene.
      However, genomic sequence analysis revealed putative binding sites for regulatory
      transcription factors upstream of the 5' end of the cDNA. Analysis of the SF1
      genomic and cDNA sequences predicts the use of duplicated 5' and 3' splice sites
      as well as exon skipping and intron inclusion to generate six SF1 mRNAs by
      alternative splicing events.

PMID- 9573337
TI  - Multiple isoforms of metallothionein are expressed in the porcine liver.
AB  - Isogenes are highly homologous to each other and are often difficult to
      ascertain, as has been the case with metallothionein, a metal-binding protein
      rich in cysteines. Conventional separation of metallothionein isoforms relied on
      ion exchange chromatography of the proteins, or screening for the sequences from
      gene libraries. In this study, a combination of RT-PCR and partial protein
      sequencing is used in the identification of metallothionein isogenes expressed in
      porcine liver. By this approach, we have identified expressed coding sequences
      which constitute 10 new isogenes. Of the four known groups of metallothioneins
      (MT), phylogenetic analyses place these pig isogenes in the MT-1 group, except
      two which are identified as being closely related to MT-2, and none in groups 3
      and 4. The isogenes are thus namedpMT-1a to -1g, andpMT-2a and -2b. While each of
      the isogene sequences is unique, two isogenes,pMT-1e1 andpMT-1e2, share an
      identical amino acid sequence, differing only in specific codons. Two others,pMT
      1b andpMT-1g, have a cysteine substituted by arginine, the first such sequence
      ever detected in MT.pMT-2a andpMT-2b are closely aligned with the MT-2 group of
      vertebrates, in spite of the absence of a characteristic acidic amino acid at
      position 10 or 11, common in other mammalian metallothioneins.

PMID- 9573338
TI  - Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix
      metalloproteinases.
AB  - Three genes potentially encoding novel matrix metalloproteinases (MMPs) were
      identified by sequence similarity searching of Caenorhabditis elegans genome
      database, and cDNAs for these MMPs were cloned. The predicted gene products (MMP
      C31,-H19 and -Y19) display a similar domain organization to human MMPs. MMP-H19
      and -Y19 are unique in that they have an RXKR motif between the propeptide and
      catalytic domains that is a furin-like cleavage site, and conserved only in
      stromelysin-3 and membrane-type MMPs. The amino acid sequence homology with MMP
      1/human interstitial collagenase at the catalytic domain is 45%, 34% and 23% for
      MMP-C31, -H19 and -Y19, respectively. Recombinant proteins of C. elegans MMPs
      cleaved an MMP peptide substrate with efficiency proportional to their amino acid
      homology with human MMPs. Digestion of gelatin was observed only with MMP-C31.
      Enzyme activity of MMP-C31 and -H19 was inhibited by human tissue inhibitor of
      MMPs (TIMP)-1, TIMP-2 and synthetic MMP inhibitors, BB94 and CT543, indicating
      that the catalytic sites of these C. elegans MMPs are structurally closely
      related with those of mammalian MMPs.

PMID- 9573339
TI  - Cloning and characterization of the mouse pituitary adenylate cyclase-activating
      polypeptide (PACAP) gene.
AB  - The gene encoding the mouse precursor of pituitary adenylate cyclase-activating
      polypeptide (PACAP) has been cloned, and its structural organization was
      determined. Using the 5'-rapid amplification of cDNA ends (RACE) procedure, three
      types of transcription initiation produced by alternative exon usage of two
      untranslated alternative exons (exons 1A and 1B) were defined. The PACAP gene
      spans 6.6kb of genomic DNA and is composed of six exons including the alternative
      exons. The signal peptide, PACAP-related peptide and mature 38-amino acid PACAP
      (PACAP-38) are encoded within exons 2, 4 and 5, respectively. The 5'-flanking
      region of the PACAP gene contains several sequence motifs homologous to cAMP
      response element, TPA response element, and growth hormone factor-1 binding site.
      A dinucleotide repeat sequence is present in an intron. In addition, there are di
      and tetranucleotide repeat sequences 2.4kb and 3.2kb upstream to the translation
      start point, respectively. The overall intron-exon organization and the
      production of the alternate mRNAs of the PACAP gene are markedly similar to those
      of the growth hormone-releasing hormone (GHRH), supporting the hypothesis that
      the two genes encoding GHRH or PACAP were originated from a gene duplication.
      Promoter analysis of the 5'-flanking region of the PACAP gene using a luciferase
      gene reporter system revealed that the isolated 5'-flanking region has functional
      promoter activity and is responsible for inducible expression.

PMID- 9573340
TI  - Genomic organization and expression of KCNJ8/Kir6.1, a gene encoding a subunit of
      an ATP-sensitive potassium channel.
AB  - ATP-sensitive K+ (KATP) channels are implicated in the coupling of metabolic
      energy to membrane potential, thereby regulating many essential cell functions.
      Here, we demonstrate that a subunit of human KATP channel, KCNJ8/Kir6.1, is
      expressed preferentially in the human heart. Somatic cell-hybrid mapping and
      fluorescence in-situ hybridization (FISH) localize human KCNJ8 to the short arm
      of human chromosome 12, at 12p12. Partial characterization of the human Kir6. 1
      gene demonstrates that there is one large intron in the coding region and at
      least two additional introns in the 5' untranslated region resulting in
      transcripts that have differential expression in human tissues examined. Our
      studies provide information on the complexity of the Kir6.1 transcript in the 5'
      UTR that may be useful for future investigations on the tissue-specific
      regulation and function of this KATP channel gene.

PMID- 9573341
TI  - Alternative splicing generates isoforms of human neuron-derived orphan receptor-1
      (NOR-1) mRNA.
AB  - Neuron-derived orphan receptor-1 (NOR-1) is a novel member of the Nur77/NGFI-B
      subfamily within the nuclear receptor superfamily. Recently, several proteins
      closely related to NOR-1 have been described. To elucidate the relationships
      between NOR-1 and these closely related proteins, we analyzed the human NOR-1
      gene and its transcripts by molecular cloning. We identified two variant NOR-1
      transcripts in human skeletal muscles. One variant has a different 5'
      untranslated region, and the other lacks C-terminal amino acid sequences
      corresponding to the putative ligand binding domain. These variant sequences
      share the common exon-intron boundary with NOR-1 mRNA, suggesting that they were
      generated from a single gene by alternative splicing, with the divergent points
      conserved between the rat and human. We also examined the promoter activities of
      the 5'-flanking regions of the two NOR-1 transcripts (NOR-1alpha and NOR-1beta
      mRNAs) by luciferase gene transfection. We demonstrated that the 5'-flanking
      region of the previously described NOR-1 gene, which has characteristics of a
      promoter found in housekeeping genes, showed potent promoter activity although
      the promoter for NOR-1beta mRNAs could not be determined.

PMID- 9573342
TI  - Genomic structure and domain organisation of the human Bak gene.
AB  - The Bcl-2 homologue, Bak, is a potent inducer of apoptosis. FISH data presented
      here located the gene to 6p21.3. Mapping was consistent with its location
      centromeric of the HSET locus and approximately 400kb from the MHC. The
      construction of a contig of genomic clones across the locus facilitated the
      sequencing of a PAC containing the gene. Comparison of the gene structure to
      functional and physical domains revealed a good agreement between the physical
      structure and the intron-exon organisation. The position of a single intron was
      conserved in comparison to other members of the Bcl-2 family, namely Bax, CED-9,
      Bcl-X and Bcl-2, but all other introns were displaced, consistent with a
      divergent phylogeny.

PMID- 9573343
TI  - Cloning and developmental regulation of tissue inhibitor of metalloproteinases-3
      (TIMP3) in Xenopus laevis early embryos.
AB  - We cloned a cDNA encoding tissue inhibitor of metalloproteinases-3 (TIMP3) from
      the frog Xenopus laevis. Similar to TIMP3 from other species, Xenopus TIMP3 has
      188 residues including 12 conserved cysteines and Asn184, a putative site for N
      linked sugars. Xenopus TIMP3 is 84% identical with human TIMP3. As shown by
      Northern blotting and RT-PCR, Xenopus TIMP3 mRNA is maternally inherited in eggs
      and midblastula (stage 8) embryos, downregulated in gastrula and then upregulated
      in neurula and pretailbud embryos. In select adult tissues, TIMP3 mRNA is present
      in heart, muscle, liver, skin, intestine and ovaries. These results suggest that
      TIMP3 is involved in the regulation of expression of matrix metalloproteinases in
      Xenopus early development and adult tissue remodeling.

PMID- 9573344
TI  - SWIM analysis allows rapid identification of residues involved in invasin
      mediated bacterial uptake.
AB  - The Yersinia pseudotuberculosis invasin protein promotes bacterial uptake into
      normally non-phagocytic cells. Combinations of six alanine substitutions in a
      region of invasin previously shown to be important for bacterial internalization
      were analyzed using binomial and codon mutagenesis strategies. A single pool of
      mutants, potentially containing 64 derivatives with various combinations of
      alanine substitutions, was enriched by one passage through HEp2 cells. DNA was
      isolated from the resulting pool of internalization-competent bacteria and
      sequenced in a single set of reactions to determine which alanine substitutions
      maintained activity. Results of the single sequencing run performed on the pool
      indicated that strains harboring the D911A substitution were absent after
      enrichment, confirming the importance of an aspartate residue at this site. When
      single clones were subsequently isolated from the pool, those containing multiple
      alanine substitutions in invasin showed uptake defects that were additive, with
      the exception of S904A/M912A and S910A/M912A double mutants. Binomial mutagenesis
      combined with a pooled enrichment and sequencing strategy, called 'SWIM'
      mutagenesis (selection without isolation of mutants), could be applied to any
      system for which there exists an enrichment scheme, using a single
      oligonucleotide pool to analyze multiple residues.

PMID- 9573345
TI  - In-frame elimination of exon 10 in Cftrtm1Unc CF mice.
AB  - Cystic fibrosis (CF) is a severe autosomal-linked inherited disease in humans.
      Transgenic CF animals play a crucial role in the study of molecular mechanisms
      underlying disease pathology. In the present study, CFTR mRNA expression was
      examined in different tissues from one CF mouse model that contains a disruption
      in exon 10 sequence of the CF transmembrane conductance regulator (CFTR) gene.
      Multiple tissue samples were collected from new-born normal (+/+), homozygous (-/
      ), and heterozygous (+/-) mice and compared for their CFTR mRNA expression. Total
      RNA samples were prepared from eight different tissues (nasal mucosa, trachea,
      lung, colon, intestine, pancreas, liver, gonads, and brain) and then analyzed by
      reverse transcription polymerase chain reaction (RT-PCR) amplification. A 329-bp
      fragment comprising exon 9 through exon 11 of the CFTR gene was amplified from
      all tissues of the normal mouse. In contrast, a 137-bp fragment was observed in
      tissue samples from homozygous CF mice. Both the 329-bp and 137-bp fragments were
      detected in samples from heterozygous mice. Direct sequencing analysis of the
      amplified fragments showed an exon 9-exon 11 splice junction, indicating that the
      entire exon 10 sequence was eliminated from homozygous CF mice. RT-PCR analysis
      of the 3' end of CFTR mRNA showed the presence of a 682-bp, exon 20-24 fragment
      in -/- and +/- mice. These results demonstrate that an alternately spliced CFTR
      mRNA is produced in this CF 'knock-out' mouse. A semi-quantitative comparison of
      the wild-type and exon 10 minus CFTR (CFTR-E10) mRNA in heterozygote animals
      indicated that less (but a detectable amount) mutant CFTR mRNA was present in all
      organs tested. There was, however, a significant reduction of CFTR-E10 mRNA in
      the liver and the pancreas. Since the deletion of exon 10 is in-frame, the
      significance of the CFTR-E10 mRNA in terms of CFTR protein and function requires
      further analysis.

PMID- 9573346
TI  - Structure and chromosomal localization of the mouse bombesin receptor subtype 3
      gene.
AB  - Bombesin (BN)-like peptides/neurotransmitters mediate a broad range of
      physiological funtions in the gastrointestinal tract and the central nervous
      system through binding to their specific, high-affinity mammalian bombesin
      receptors. This family of heptahelical, G-protein coupled receptors includes the
      gastrin-releasing peptide receptor (GRP-R, or bb2), neuromedin B receptor (NMB-R,
      or bb1), and the bombesin receptor subtype 3 (BRS-3, or bb3). The tissue
      distribution of BRS-3 is quite dissimilar compared to the other two BN receptors,
      GRP-R and NMB-R, and a natural ligand for BRS-3 is currently unknown. Nothing is
      known about mechanisms regulating BRS-3 gene expression and possible association
      with disease. To gain insight into the underlying structure and chromosomal
      localization of the BRS-3 genes, bacteriophage P1 genomic clones, harboring the
      genes for the human and mouse BRS-3, respectively, were isolated and their
      structure and chromosomal localizations determined. The protein-coding region of
      both genes is divided into three exons and spans approximately 5kb. The loci of
      the BRS-3 genes were mapped to a syntenic region of the human (Xq25) and mouse
      (XA7.1-7.2) X-chromosome, respectively. The structural data of the BRS-3 genes
      derived from this study will permit future investigations of the mechanisms
      regulating their expression.

PMID- 9573347
TI  - Cellular calcium in health and disease.

PMID- 9573348
TI  - A human homolog of the yeast CDC7 gene is overexpressed in some tumors and
      transformed cell lines.
AB  - The Cdc7 protein kinase of Saccharomyces cerevisiae is a critical regulator of
      several aspects of DNA metabolism and cell cycle progression. We describe the
      isolation of a human gene encoding a Cdc7 homolog. The Cdc7Hs protein sequence is
      27% identical to that of the yeast protein, includes features unique to yeast
      Cdc7, and contains all conserved catalytic residues of protein kinases. The human
      sequence also shows significant similarity to the cyclin-dependent kinases, in
      accordance with evidence that yeast Cdc7 is related to the cdks. CDC7Hs is
      expressed in many normal tissues, but overexpressed in certain tumor types and
      all transformed cell lines examined. In some of the tumors tested, CDC7Hs
      expression correlates with expression of a proliferation marker, the histone H3
      gene. In other cases, no such correlation was observed. This suggests that CDC7Hs
      expression may be associated hyperproliferation in some tumors and neoplastic
      transformation in others.

PMID- 9573349
TI  - Tissue-specific chromatin structure at the hepatocyte growth factor/scatter
      factor gene promoter.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a recently characterised
      molecule with many remarkable functions. Its involvement in important processes
      such as cell proliferation, cell migration, morphogenesis and organ development
      implies that its activity should be tightly regulated. To understand the
      molecular mechanisms controlling HGF/SF transcription, we have analysed DNaseI
      hypersensitive sites (DHS) along rat and human HGF/SF genes in various tissues
      and cell types. We identified five DHS along the rat gene, two in the 5'-flanking
      region and three in the first intron. These sites are only found in rat tissues
      and rat cell lines, which express HGF/SF. The strongest hypersensitive site map
      to a region that corresponds to the promoter by start site analysis. A single
      tissue-specific DHS is present in human cell lines that express HGF/SF and
      corresponds to the promoter region. Our results suggest that chromatin
      accessibility plays a major role in the regulation of HGF/SF transcription
      regulation.

PMID- 9573350
TI  - Cloning, biological characterization and high-level expression of rat interleukin
      3 using recombinant adenovirus: description of a new splicing variant.
AB  - In the present study, we describe the cloning and sequence analysis of rat IL-3.
      Two different mRNA isoforms were isolated after transfection of COS cells with
      the cytokine genomic sequences. One of the isoforms has been predicted before by
      Cohen et al. (1986), and the other one is identical except that it encodes a
      protein with an insertion of three amino acids at position 56. As names for the
      two isoforms, we propose IL-3alpha for the predicted and IL-3beta for the novel
      molecule. IL-3beta mRNA was detected as the predominant isoform in rat
      lymphocytes in vivo. High levels of the cytokine were obtained after infection of
      human cells (A549) with a recombinant adenovirus harboring rIL-3beta cDNA
      (IG.Ad.CMV.IL-3beta). The biological properties of the IL-3beta protein were
      tested in a FDC-P1 proliferation assay and in a hematopoietic progenitor colony
      forming assay. To assess in-vivo bioactivity, lysed 293 cells containing
      IG.Ad.CMV.rIL-3beta virus were injected subcutaneously into F344 rats.
      Stimulation of hematopoiesis and leucocytosis were observed during the treatment.
      After subcutaneous injections of the lysed adeno-producer cells in mice, the only
      effect observed was a cellular infiltration at the site of injection, confirming
      the poor cross-reactivity between the two species. The biological properties in
      vitro and in vivo demonstrate that the cDNA sequences of IL-3beta presented here
      encode active rat IL-3 protein.

PMID- 9573351
TI  - Sickle hemoglobin is more fusogenic than normal hemoglobin at physiological pH
      and ionic strength conditions.
AB  - We used electron microscopy, quasi-elastic light scattering and static light
      scattering to show that human hemoglobin (Hb) interacts with bovine brain
      phosphatidylserine lipid vesicles and promotes vesicle fusion in an isotonic
      buffer at pH 7.4. The fusogenic properties of Hb were observed in both small
      unilamellar vesicles (SUVs) and large unilamellar vesicles (LUVs). A simple
      turbidity measurement method was used to follow increases in vesicle size
      (scattering diameter) as a function of time. For the first 3 h, upon incubation
      with oxygenated Hb, the scattering diameters of vesicles increased at a rate of
      7.8 nm/h for LUVs. Continuous incubation with Hb led to complicated vesicle
      fusion, probably due to the oxidation products of Hb and lipid molecules. In the
      absence of both Hb and lipid oxidation, using Hb liganded with carbon monoxide,
      we obtained, for the entire 20 h incubation period, a fusion rate of 2.9 nm/h for
      LUVs. We also studied interactions between sickle Hb and vesicles under the same
      conditions and found that the vesicle fusion rates for sickle Hb were about 2
      times faster than those for normal Hb. These results showed that sickle Hb
      exhibited more extensive interactions with lipid bilayer than normal Hb at
      physiological pH and ionic strength conditions, and provide insights toward
      understanding the molecular mechanisms in sickle cell abnormalities.

PMID- 9573352
TI  - Characterization of the flanking regions of the S-RNase genes of Japanese pear
      (Pyrus serotina) and apple (Malus x domestica).
AB  - Genomic sequences of the self-incompatibility genes, the S-RNase genes, from two
      rosaceous species, Japanese pear and apple, were characterized. Genomic Southern
      blot and sequencing of a 4.5-kb genomic clone showed that the S4-RNase gene of
      Japanese pear is surrounded by repetitive sequences as in the case of the S-RNase
      genes of solanaceous species. The flanking regions of the S2- and Sf-RNase genes
      of apple were also cloned and sequenced. The 5' flanking regions of the three
      alleles bore no similarity with those of the solanaceous S-RNase genes, although
      the position and sequence of the putative TATA box were conserved. The putative
      promoter regions of the Japanese pear S4- and apple Sf-RNase genes shared a
      stretch of about 200bp with 80% sequence identity. However, this sequence was not
      present in the S2-RNase gene of apple, and thus it may reflect a close
      relationship between the S4- and Sf-RNase genes rather than a cis-element
      important in regulating gene expression. Despite the uniform pattern of
      expression of the rosaceous S-RNase genes, sequence motifs conserved in the 5'
      flanking regions of the three alleles were not found, implying that the cis
      element controlling pistil specific gene expression also locates at the
      intragenic region or upstream of the analyzed promoter region.

PMID- 9573353
TI  - Pathological changes in levels of three small stress proteins, alphaB crystallin,
      HSP 27 and p20, in the hindlimb muscles of dy mouse.
AB  - Using three different analyses, we investigated the levels of the three small
      stress proteins alphaB crystallin, HSP 27 and p20 in the slow-twitch soleus
      muscle and fast-twitch tibialis anterior muscle of normal and dy mice. All of
      these analyses (immunoassay, Western blot and immunohistochemistry) showed
      markedly increased levels of these stress proteins in fast-twitch type muscle
      (tibialis anterior muscle) of dy mouse. In contrast, the levels of alphaB
      crystallin, HSP 27 and p20 of dy mouse were reduced in slow-twitch type muscle
      (soleus muscle). Manipulation of this protective response may reduce injury and
      may have potential therapeutic application in congenital muscular dystrophy
      (CMD), which possesses a deficiency of laminin-alpha2 chain in muscle fiber
      basement similar to dy mouse.

PMID- 9573354
TI  - Genomic structure and sequence of the pufferfish (Fugu rubripes) gene encoding an
      actin-related protein.
AB  - Using a polymerase chain reaction (PCR)-generated gene fragment as a probe, we
      isolated and sequenced a gene encoding an actin-related protein belonging to the
      Arp3 family from the pufferfish, Fugu rubripes. The Fugu Arp3 gene spans 3.7kb
      from the transcription start site to the polyadenylation signal. This is the
      first report of the genomic sequence of a vertebrate Arp3 gene. The Fugu Arp3
      gene consists of 12 exons and 11 introns compared to Drosophila homologue, which
      has six exons and five introns. The protein sequence encoded by the Fugu gene is
      97% and 80% identical to bovine and Drosophila homologues, respectively. The Fugu
      Arp3 gene is expressed in a wide range of tissues, with higher levels detected in
      the gills, kidney, ovary, skin and testis. Three different size transcripts of
      the Arp3 gene (1.4kb, 1.8kb and 2.2kb) were identified in various tissues.

PMID- 9573355
TI  - 17beta-oestradiol enhances release of matrix metalloproteinase-2 from human
      vascular smooth muscle cells.
AB  - Vascular remodelling occurs during all stages of atherosclerotic progression.
      Anti-atherosclerotic drugs may function by restoring regulation of the processes
      involved in remodelling of the extracellular matrix. A key group of enzymes
      involved in these processes are the matrix metalloproteinases (MMPs). Oestrogens
      have been demonstrated to possess anti-atherosclerotic properties at low
      concentrations while being associated with lesion formation at high
      concentrations. We examined the effect of 17beta-oestradiol on MMP-2 expression
      in human coronary artery (CAVSMC) and umbilical artery vascular smooth muscle
      cells (UAVSMC). MMP-2 expression was measured by chemiluminescent immunoblotting
      and quantified by laser densitometry. pro-MMP-2 was secreted by VSMCs and
      increasing levels of 17beta-oestradiol, from physiological through
      supraphysiological, were associated with significant dose-dependent increases in
      MMP-2 levels in culture media. This effect was dependent on de novo protein
      synthesis and could be antagonised by the oestrogen receptor antagonist,
      tamoxifen, and the specific receptor antagonist ICI 182, 780. 17beta-Oestradiol
      appears to be a specific stimulator of MMP-2 release from human vascular cells.
      The concentration dependence of this effect suggests a basis for the differential
      effects of low and high oestrogen levels on vascular integrity.

PMID- 9573356
TI  - Characterization of Actinobacillus actinomycetemcomitans leukotoxin pore
      formation in HL60 cells.
AB  - The mechanism of cell death induced by Actinobacillus actinomycetemcomitans
      leukotoxin (LTX) has been investigated with flow cytometry and patch electrode
      recording using cultured HL60 cells. The kinetics of propidium iodide (PI)
      positive staining of HL60 cells was measured as a function of LTX concentration
      at 37 degreesC. Results showed a concentration-dependent decrease in the tk
      times. Cell kill was slow at <1 microg/ml LTX concentrations with fewer than 50%
      of the cells killed after 1 h; at 1 microg/ml, the tk times ranged from
      approximately 15 to 30 min. At higher concentrations, the tk times decreased
      rapidly. The rate of cell kill was appreciably slowed at 20 degreesC. HL60 whole
      cell currents were recorded with patch electrodes. Immediately following exposure
      to high concentrations of LTX, large currents were recorded suggesting that the
      membrane potential of these cells had collapsed due to the large conductance
      increases. At low toxin concentrations, rapid conductance fluctuations were seen
      suggestive of a limited number of toxin-mediated events. Cells exposed to low
      concentrations of LTX exhibited these conductance fluctuations for up to 1 h,
      whereas toxin-insensitive cells were unaffected by long exposures to high
      concentrations of toxin. Our results are consistent with LTX-induced pores in
      susceptible cells which overwhelm the ability of the cell to maintain osmotic
      homeostasis causing cell death.

PMID- 9573357
TI  - Analysis of the Plasmodium vivax dihydrofolate reductase-thymidylate synthase
      gene sequence.
AB  - A basis for the intrinsic resistance of some Plasmodium vivax isolates to
      pyrimethamine is suggested following the isolation of the bifunctional gene
      encoding dihydrofolate reductase-thymidylate synthase (DHFR-TS) of this human
      malaria parasite. Malaria parasites are dependent on this enzyme for folate
      biosynthesis. Specific inhibition of the DHFR domain of the enzyme by
      pyrimethamine blocks pyrimidine biosynthesis, leading to an inhibition of DNA
      replication. The gene was isolated by the polymerase chain reaction (PCR) from
      genomic DNA using degenerate oligonucleotides designed to hybridize on the highly
      conserved regions of the sequence. The nucleotide sequence was completed by
      screening P. vivax genomic bank. Sequence analysis revealed an open reading frame
      (ORF) of 1872 nucleotides encoding a deduced protein of 623 amino acids (aa).
      Alignment with other malarial DHFR-TS genes showed that a 237-residue DHFR domain
      and a 286-residue TS domain were separated by a 100-aa linker region. Comparison
      with other malarial species showed low and essentially no isology in the DHFR and
      junctional domains, respectively, whereas an extensive isology was observed in
      the TS domain. The characteristic features of the P. vivax DHFR-TS gene sequence
      include an insertion of a short repetitive tandem array within the DHFR domain
      that is absent in another human malaria parasite, P. falciparum, and a GC-biased
      aa composition, giving rise to highly GC-rich DHFR (50.8%), junctional (58.7%),
      and TS (40.5%) domains, as compared with other malaria parasites. Analysis of the
      5' noncoding region revealed the presence of a putative TATA box at 116
      nucleotides upstream of the ATG start codon as well as a putative GC box at -636.
      Comparison of the DHFR sequences from pyrimethamine-sensitive and pyrimethamine
      resistant P. vivax isolates revealed two residue changes: Ser Arg-58 and Ser Asn
      117. These aa residues correspond to codons 59 and 108 in the P. falciparum DHFR
      active site in which similar aa substitutions (Cys Arg-59 and Ser Asn-108) are
      associated with pyrimethamine resistance. These findings may explain the
      intrinsic resistance of some P. vivax isolates to pyrimethamine.

PMID- 9573358
TI  - Rapid identification of Leishmania species from formalin-fixed biopsy samples by
      polymorphism-specific polymerase chain reaction.
AB  - The precise identification and classification of Leishmania species is important
      for public health surveillance since different species cause different clinical
      features of the disease. A highly specific polymerase chain reaction (PCR) panel
      was developed to enable the identification of the five major Leishmania species
      that cause New World cutaneous leishmaniases. The primers used for this panel
      were designed to distinguish the polymorphism in sequences of commonly amplified
      DNA bands of the parasites produced by arbitrarily primed PCR. These polymorphism
      specific PCR diagnoses were performed with formalin-fixed biopsy specimens of the
      leishmanial lesions from four patients in Ecuador and one hamster skin lesion,
      and these lesions were determined to be caused by Leishmania (Viannia)
      panamensis, L. (Leishmania) mexicana, and L. (L.) amazonensis. The PCR panel may
      offer an important and practical approach to the standardized identification of
      Leishmania species in field examinations.

PMID- 9573359
TI  - Channel properties of NMDA receptors on magnocellular neuroendocrine cells
      cultured from the rat supraoptic nucleus.
AB  - Application of N-methyl-D-aspartate (NMDA) to the supraoptic nucleus of the
      hypothalamus (SON) generates clustered firing that may be important in hormone
      release. However, synaptically evoked EPSPs recorded from SON neurons exhibit
      varying contributions from NMDA receptors. We used the high resolution of single
      channel recording to examine the receptor and ion channel properties of NMDA
      receptors expressed by SON neurons in 'punch' culture. Biocytin introduced into
      individual neurons during patch clamp recording revealed large (32.1+/-3.3
      micron), oblong somas and bipolar extensions typical of magnocellular
      neuroendocrine cells (MNCs). Rapid application of NMDA (100-300 microM) in the
      presence of 10 microM glycine to outside-out macropatches resulted in openings
      with an average conductance of 46. 9 pS and reversal potential of +3.9 mV.
      Increasing glycine from 0.03 to 30 microM increased the apparent frequency,
      duration and occurrence of overlapping NMDA-elicited openings. NMDA responses
      were inhibited by Mg2+ in a voltage-dependent manner and by the NMDA-site
      antagonist, D-(-)-2-amino-5-phosphonovaleric acid (D-APV). Application of
      saturating NMDA or glycine alone with the glycine-site antagonist, 5,7
      dichlorokynurenate (DCK) or with D-APV, respectively, did not result in agonist
      induced openings. NR1 immunoreactivity was observed in large neurons (>25 micron)
      with MNC-like morphology. These single-channel and immunocytochemical data
      confirm the presence of functional NR1-containing NMDA receptors in MNCs.

PMID- 9573360
TI  - Cloning of the gene encoding the murine clathrin-associated adaptor medium chain
      mu 2: gene organization, alternative splicing and chromosomal assignment.
AB  - The mu 2 chain of the clathrin-associated adaptor complex AP-2 is a member of the
      adaptor medium chain family, a group of proteins involved in the sorting of
      integral membrane proteins in endocytic/exocytic pathways. Here, we report the
      cloning of the (MMU)CLAPM1 gene encoding the murine mu 2 chain, the first member
      of the family for which this information has become available. The mu 2 gene is
      approximately 8.5 kb long and is organized into 12 exons and 11 introns. Two
      transcripts are generated by alternative splicing of exon 5, a mini-exon of only
      six nucleotides. Proteins encoded by both transcripts are capable of interacting
      with tyrosine-based sorting signals, suggesting that they are functionally
      equivalent. The mu 2 gene is localized to the proximal region of mouse chromosome
      16, which is syntenic to the proximal region of human chromosome 3. The isolation
      and characterization of the mu 2 gene should be instrumental for future studies
      of the genetics and physiological role of the adaptor medium chains in mammals.

PMID- 9573361
TI  - Biochemical and immunochemical properties of B lymphocyte cytochrome b558.
AB  - Like neutrophils, Epstein-Barr virus (EBV)-immortalized B lymphocytes express all
      constituents of the NADPH oxidase complex necessary to generate superoxide anion
      O2-. The NADPH oxidase activity in EBV-B lymphocytes is only 5% of that measured
      in neutrophils upon PMA stimulation. Cytochrome b558 is the sole redox membrane
      component of NADPH oxidase; it is the protein core around which cytosolic factors
      assemble in order to mediate oxidase activity. In the present study, we have
      compared the structural and functional properties of cytochrome b558 from EBV-B
      lymphocytes and neutrophils. Cytochrome b558 from EBV-B lymphocyte plasma
      membrane, like that from neutrophils, is characterized by a heterodimeric
      structure with a highly glycosylated beta subunit, known as gp91-phox. While the
      amount of cytochrome b558 recovered after purification from EBV-B lymphocytes
      (approximately 0.24 nmol from 1010 cells) was low compared to that recovered from
      neutrophils (approximately 10 nmol), the biochemical properties of purified
      cytochrome b558 from both EBV-B lymphocytes and neutrophils were quite similar
      with respect to their differential spectra, redox potential, and FAD binding
      site. Once cytochrome b558 was extracted from the EBV-B lymphocyte membrane, it
      was able to mediate, in a reconstituted system of O2- production the same oxidase
      turnover as that found for cytochrome b558 extracted from neutrophils. A
      comparison between membrane bound and soluble cytochrome b558 suggested that the
      weak oxidase activity measured in intact EBV-B cells might be the result not only
      of the small amount of expressed cytochrome b558, but also of a defect of the
      activation process in lymphocyte membrane.

PMID- 9573362
TI  - NGF delays rather than prevents the cholinergic terminal damage and delayed
      neuronal death in the hippocampus after ischemia.
AB  - Cerebral ischemia induces damage of cholinergic terminals in the hippocampus,
      which preceded the delayed neuronal death (DND) of the CA1 pyramidal cells. We
      investigated the effects of nerve growth factor (NGF) on the cholinergic terminal
      damage after ischemia. Continuous NGF infusion (0.5 microg/7 days) into the
      lateral ventricle before and after 5 min ischemia prevented a decrease in choline
      acetyltransferase (ChAT)-immunoreactivity and disturbance of acetylcholine (ACh)
      release on the 4th day after ischemia, but not on day 7, i.e., NGF infusion
      caused delay in the progress of the cholinergic terminal damage. These findings
      show that the cholinergic terminal damage may result from deficiency of
      endogenous NGF in an ischemic brain. In addition, we investigated whether NGF
      would prevent the DND after ischemia. NGF infusion also caused delay in the
      progress of the DND until day 14. Our results suggested that the neuroprotective
      effect of NGF on the DND may be secondarily yielded by maintenance of
      communication between cholinergic terminal and the target CA1 cell, and that
      prevention of cholinergic terminal damage may be useful for the treatment of
      cerebrovascular disease.

PMID- 9573363
TI  - Spermine is not essential for growth of Saccharomyces cerevisiae: identification
      of the SPE4 gene (spermine synthase) and characterization of a spe4 deletion
      mutant.
AB  - Spermine, ubiquitously present in most organisms, is the final product of the
      biosynthetic pathway for polyamines and is synthesized from spermidine. In order
      to investigate the physiological roles of spermine, we identified the SPE4 gene,
      which codes for spermine synthase, on the right arm of chromosome XII of
      Saccharomyces cerevisiae and prepared a deletion mutant in this gene. This mutant
      has neither spermine nor spermine synthase activity. Using the spe4 deletion
      mutant, we show that S. cerevisiae does not require spermine for growth, even
      though spermine is normally present in the wild-type organism. This is in
      striking contrast to the absolute requirement of S. cerevisiae for spermidine for
      growth, which we had previously reported using a mutant lacking the SPE3 gene
      (spermidine synthase) [Hamasaki-Katagiri, N., Tabor, C. W., Tabor, H., 1997.
      Spermidine biosynthesis in Saccharomyces cerevisiae: Polyamine requirement of a
      null mutant of the SPE3 gene (spermidine synthase). Gene 187, 35-43].

PMID- 9573364
TI  - A splice variant of trkB and brain-derived neurotrophic factor are co-expressed
      in retinal pigmented epithelial cells and promote differentiated characteristics.
AB  - There is evidence suggesting reciprocal trophic interactions between
      photoreceptors and the retinal pigmented epithelium (RPE), but the factors
      involved have not been identified. In this study, we investigated the hypothesis
      that one or more known neurotrophic factors act upon the RPE. Cultured human and
      freshly isolated bovine RPE cells demonstrated saturable specific binding for
      [125I]labeled BDNF, NT-4/5 and NT-3 with little specific binding for CNTF and
      none for NGF. Cross-competition experiments showed that BDNF is the preferred
      ligand and cross-linking of [125I]BDNF resulted in a doublet at 160 kd that was
      increased in RPE cells incubated in all-trans retinoic acid. There was basal
      phosphorylation of a 145 kd protein recognized by an anti-trk antibody that was
      increased in RPE cells pulsed with BDNF. RT-PCR with primers spanning the
      transmembrane domain demonstrated that RPE cells express trkB mRNA lacking a
      region homologous to exon 9 of chicken trkB, a splice variant that has been
      demonstrated to preferentially interact with BDNF. Northern blots demonstrated
      that cultured RPE cells also express mRNA for BDNF. BDNF did not stimulate
      proliferation or increase survival of RPE cells in serum-free medium, but
      promoted a differentiated morphology and increased the expression of cellular
      retinaldehyde binding protein, a marker of the differentiated state in RPE cells.
      An RPE cell line that spontaneously shows differentiated features showed a high
      level of BDNF mRNA. These data demonstrate that RPE cells express a short splice
      variant of trkB whose activation correlates with expression of differentiated
      characteristics and the cells themselves are capable of producing a ligand for
      the receptors. Signaling through trkB could play a role in differentiation of RPE
      cells during development and maintenance of the differentiated state in adult
      RPE.

PMID- 9573365
TI  - Gene fragment polymerization gives increased yields of recombinant human
      proinsulin C-peptide.
AB  - A multimerization strategy to improve yields upon recombinant production of the
      31-aa human proinsulin C-peptide is presented. Gene fragments encoding the C
      peptide were assembled using specific head-to-tail multimerization. DNA
      constructs encoding one, three or seven copies of the C-peptide gene, fused to a
      serum albumin binding affinity tag, were expressed intracellularly in Escherichia
      coli. The three fusion proteins were produced at similar levels (approximately 50
      mg/l) and were proteolytically stable during production. Enzymatic digestion by
      trypsin-carboxypeptidase B treatment of the fusion proteins was shown to
      efficiently release native C-peptide, as determined by mass spectrometry, reverse
      phase chromatography and a radioimmunoassay. The quantitative yields of C-peptide
      obtained from the three different fusion proteins suggest that this
      multimerization strategy could provide a cost-efficient production scheme for the
      C-peptide, and that this strategy could be useful also for production of other
      recombinant peptides.

PMID- 9573366
TI  - Differential expressions of mRNA for proteoglycans, collagens and transforming
      growth factor-beta in the human cervix during pregnancy and involution.
AB  - During pregnancy and involution, an extensive remodelling of the human cervical
      connective tissue occurs. This cervical ripening is one of the most pronounced
      physiological remodelling processes known in human connective tissue. To
      investigate how the remodelling is accomplished, the levels of mRNA for collagen
      I and III, versican and three small proteoglycans, biglycan, decorin and
      fibromodulin, were evaluated using Northern blots at different stages of cervical
      ripening. In the corresponding biopsies the concentration of collagen and of
      small and large proteoglycans were determined. The role of transforming growth
      factor-beta (TGF-beta) as a mediator of the remodelling process was also
      investigated. The concentration of collagen decreased and 1 week before partus,
      50% of the nonpregnant level was attained. No further decrease was noted after
      partus. The mRNA for collagen I and III did, however, not decrease in the term
      pregnant cervix 1 week before partus. Only 20-30% decrease during the final
      ripening just before partus was recorded. Neither did the mRNA levels of the
      small proteoglycans change significantly during the ripening, despite an almost
      50% decrease in the concentration of the small proteoglycans. The message for
      versican was, however, 5-fold increased at partus and then gradually returned to
      nonpregnant levels within 4 days after delivery. These changes corresponded to
      similar changes in the concentration of the large proteoglycan. Thus, the
      remodelling of the cervical connective tissue is achieved by two different
      mechanisms, on one hand an increased turnover of collagen and the small
      proteoglycans, on the other a changed transcription followed by an increased
      production of versican. During the involution 2- to 3-fold increases in the
      messages for collagen I and III, and the small proteoglycans, biglycan and
      decorin, corresponded to increases in the concentration of the small
      proteoglycans and non-extractable collagen. The message for TGF-beta was
      increased 2-fold immediately after delivery compared with the term pregnant
      state. Thus, TGF-beta may be of importance for the reconstruction of the cervix,
      which starts immediately after partus.

PMID- 9573367
TI  - Cloning and sequencing of a gene encoding cellobiose dehydrogenase from Trametes
      versicolor.
AB  - Cellobiose dehydrogenase (CDH) is an enzyme produced under lignocellulose
      degrading conditions by Trametes versicolor strain 52J (Tv) and several other
      wood-degrading fungi, including Phanerochaete chrysosporium (Pc). In order to
      understand better the nature and properties of this enzyme, we isolated a genomic
      clone of Tv cdh using heterologous probes derived from the sequence of Pc cdh.
      DNA sequence analysis revealed that Tv cdh consists of 3091 bp of coding sequence
      interrupted by 14 introns. Southern blotting showed that the gene was present in
      a single copy in the strain of Tv analyzed. Tv cdh was shown by Northern blot
      analysis to be expressed as a single transcript under cellulolytic conditions. RT
      PCR of poly(A)+ RNA isolated under cellulolytic conditions was used to generate a
      near full-length cDNA copy of the cdh mRNA. The deduced protein encoded by Tv cdh
      consists of 768 amino acids (aa), including a predicted 19 aa signal peptide. The
      protein had 73% identity to the corresponding protein from Pc, which is the only
      other CDH-encoding gene that has been cloned. Based upon its deduced primary
      structure and alignment to similar sequences, Tv CDH shares a general structural
      organization with Pc CDH and other hemoflavoenzymes. Amino acid residues H-109
      and M-61 in the N-terminal heme domain are hypothesized to function in heme
      binding; the C-terminal flavin domain contained a consensus sequence for flavin
      binding between residues 217-222. Although the protein is known to bind to
      cellulose, no obvious homology to bacterial or fungal cellulose binding domains
      was observed. However, a strong homology was observed to a region of Pc CDH that
      is hypothesized to be involved in cellulose binding.

PMID- 9573368
TI  - Influence of dietary zinc on convulsive seizures and hippocampal NADPH diaphorase
      positive neurons in seizure susceptible EL mouse.
AB  - Adequate, high and deficient dietary levels of zinc (Zn) were compared in seizure
      susceptible EL mice with respect to convulsions and to nicotinamide adenine
      dinucleotide phosphate (NADPH) diaphorase-positive hippocampal neurons.
      Diaphorase positivity is associated with nitric oxide (NO) production. Convulsive
      seizures in the EL mice given the various diets did not differ over 1-4 weeks,
      but convulsions in EL mice given the Zn-deficient diet for 4 weeks were more
      effectively suppressed by injection of zonisamide (ZNS) (75 mg/kg
      intraperitoneally) than in mice receiving high- or adequate-Zn diet for the same
      period. Numbers of NADPH diaphorase-positive neurons in the CA1/CA2 region of the
      hippocampal formation were significantly higher in mice given the Zn-deficient
      diet for 4 weeks than in mice fed adequate Zn. Mice receiving the high-Zn diet
      for the same period had significantly fewer NADPH diaphorase-positive neurons in
      the subiculum than mice with adequate Zn. These results suggest that Zn
      deficiency inhibits convulsive seizures of EL mice, and that dietary Zn
      influences numbers of NO producing neurons in the hippocampal formation.

PMID- 9573369
TI  - COS cell expression studies of P86L, P86R, P480L and P480Q Hunter's disease
      causing mutations.
AB  - Three missense mutations identified in the IDS gene of our Hunter's disease
      patients (P86L, P480L and P480Q) and the previously described P86R mutation were
      expressed in COS cells to evaluate their functional consequence on iduronate-2
      sulfatase (IDS) activity and processing. The 86-proline residue belongs to the
      highly conserved pentapeptide C-X-P-S-R in which cysteine modification to a
      formylglycine is required for sulfatase activity. The substitution of the 86
      proline residue led to a severe mutation as no mature form was targeted to the
      lysosome in agreement with the severe phenotype observed in patients carrying
      P86L and P86R mutations. Expression studies with P480L and P480Q mutant cDNAs
      showed the presence of a small amount of 55 kDa mature form in the lysosomes of
      transfected COS cells. IDS activity of the P480L and P480Q mutants in cell
      extracts represents 16.6% and 5.4% of the wild-type, respectively.

PMID- 9573370
TI  - The clock in the mouse retina: melatonin synthesis and photoreceptor
      degeneration.
AB  - Melatonin is synthesized rhythmically under control of circadian oscillators by
      the retinas of non-mammalian vertebrates. Here we report that the retinas of some
      strains of laboratory mice exhibit robust circadian rhythms of melatonin
      synthesis which can be entrained by light in vitro. The rd mutation results in
      progressive loss of the rod and later cone photoreceptors. In mice homozygous for
      rd retinal melatonin synthesis is rhythmic at postnatal day 28 but not in older
      animals. Apparently rod photoreceptors are necessary for the expression of the
      circadian rhythm of melatonin synthesis but not for the synthesis itself. The
      many genetic and molecular tools available in the mouse can now be applied to
      analysis of the retinal circadian oscillator.

PMID- 9573371
TI  - Phylogenetic position of symbiotic protist Dinenympha [correction of Dinemympha]
      exilis in the hindgut of the termite Reticulitermes speratus inferred from the
      protein phylogeny of elongation factor 1 alpha.
AB  - The phylogenetic position of the symbiotic oxymonad Dinenympha exilis, found in
      the hindgut of the lower termite Reticulitermes speratus, was determined by
      analysis of translation elongation factor 1 alpha (EF-1 alpha). cDNA
      corresponding to a major part of the amino acid coding region of EF-1 alpha mRNA
      was amplified by the reverse transcription polymerase chain reaction (RT-PCR)
      method from total mRNA of termite hindgut microorganisms without cultivation. The
      product was cloned into a plasmid vector, pGEM-T, and the clones were isolated
      and sequenced. One of the EF-1 alpha clones isolated was assigned to the protist
      D. exilis by whole-cell in-situ hybridization using a specific oligonucleotide
      probe with enzymatic signal amplification. The deduced amino acid sequence was
      aligned with those of other eukaryotic and archaeabacterial EF-1 alpha s, and the
      phylogenetic relationships among early branching eukaryotes were inferred by
      using the distance matrix method and the maximum parsimony method. The
      phylogenetic analysis indicated that the D. exilis offshoot occurred before
      mitochondria-containing organisms and D. exilis branched out after the
      diplomonads clade. These results indicate that the oxymonad D. exilis is one of
      the early branching organisms and suggest that the oxymonads form a lineage
      independent of other early branching organisms.

PMID- 9573372
TI  - Electrophysiological and immunocytological demonstration of cell-type specific
      responses to hypoxia in the adult cat carotid body.
AB  - We have recently shown two types of cat carotid body cells based on the oxygen
      sensitivity of voltage-gated potassium channels. In the present study, we
      attempted to determine the correlation between cell types (glomus cells, sheath
      cells, and subtypes of glomus cells) and oxygen sensitivity of potassium
      channels. Further, changes in membrane potentials in response to hypoxia were
      also examined. Carotid body cells harvested from adult cats were cultured, and a
      whole cell patch clamp method was applied to determine the oxygen sensitivity of
      outward current. The tested cells were identified by Lucifer Yellow in the patch
      pipette. Glomus cells and sheath cells were immunocytochemically identified using
      tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) as markers.
      The cells whose outward current was inhibited by hypoxia showed TH
      immunoreactivity but not GFAP-immunoreactivity. The cells whose outward current
      was not sensitive to hypoxia were GFAP-positive or TH-negative. One TH-positive
      cell had oxygen-insensitive outward current. The resting membrane potentials of
      the cells having oxygen-sensitive outward current were significantly higher (
      55+/-3 mV) than those of the cells having oxygen-insensitive outward current (
      35+/-2 mV). The former type of cells was depolarized during hypoxia, but not the
      latter type of cells. These results suggest that most glomus cells of the adult
      cat carotid body possess oxygen-sensitive potassium channels and are depolarized
      in response to hypoxia. On the other hand, sheath cells and possibly a small
      fraction of glomus cells possess oxygen-insensitive potassium channels and their
      membrane potential is not affected by hypoxia.

PMID- 9573373
TI  - Identification, sequence and developmental expression of invertebrate flotillins
      from Drosophila melanogaster.
AB  - Caveolae are vesicular organelles that represent a sub-compartment of the plasma
      membrane. Caveolins (Cav-1, -2 and -3) and flotillins (FLO-1 and FLO-2 [also
      known as epidermal surface antigens (ESAs)] are two families of mammalian
      caveolae-associated integral membrane proteins. Although a caveolin gene family
      has recently been described in the invertebrate Caenorhabditis elegans, it
      remains unknown as to whether flotillin homologues exist in invertebrates. Here,
      we report the identification, cDNA sequence and embryonic expression pattern of
      the first invertebrate flotillin, i.e. flotillin from Drosophila melanogaster
      (FLODm). FLODm is most closely related to mammalian flotillin-1. Remarkably, the
      invertebrate FLODm protein behaves like mammalian flotillins and is targeted to
      the caveolae-enriched membrane fraction after transient expression in mammalian
      cells. Localization of the FLODm message in D. melanogaster embryos reveals that
      expression of FLODm is confined primarily to the developing nervous system. This
      is consistent with our previous observation that mammalian flotillin-1 mRNA and
      protein is expressed abundantly in brain tissue. Interestingly, the FLODm gene is
      localized to chromosomal region 52 B1-B2. In addition, we find that at least two
      flotillin-related genes are expressed in D. melanogaster. Our current results
      provide a starting point and systematic basis for dissecting the role of
      flotillin in caveolae and neuronal development using Drosophila as a genetic
      system.

PMID- 9573374
TI  - The human RIL gene: mapping to human chromosome 5q31.1, genomic organization and
      alternative transcripts.
AB  - The ril gene encoding a LIM domain protein of an unknown function was previously
      identified by differential expression cloning as a candidate tumor suppressor
      gene in rat fibroblasts (Kiess, M., Scharm, B., Aguzzi, A., Hajnal, A., Klemenz,
      R., Schwarte-Waldhoff, I., Schafer, R., 1995. Expression of ril, a novel LIM
      domain gene, is down-regulated in HRAS-transformed cells and restored in
      phenotypic revertants. Oncogene 10, 61-68). Searching for novel genes on human
      chromosome 5q31.1 by the cDNA selection technique, we isolated a cDNA clone
      identical with the cDNA of the human RIL gene (GenBank Accession No. X93510). The
      human 5q31.1 region is of interest because it contains the cytokine gene cluster
      and is frequently deleted in the malignant cells of patients with myelodysplasia
      and myeloid leukemia. Using Southern blot analysis and restriction mapping of
      genomic YAC (yeast artificial chromosome) and cosmid clones, we located the human
      RIL gene 240-260 kb telomeric to the IRF1 gene and characterized its genomic
      structure. PCR analysis indicated the presence of two alternative RIL transcripts
      in human fetal brain mRNA. The major transcript is identical with the RIL cDNA
      previously deposited in GenBank and contains seven exons distributed over 14.5 kb
      of genomic DNA with the two last 3'-exons coding a LIM domain. The minor
      transcript lacks the sixth exon compared with the major transcript, which leads
      to the loss of the LIM domain. We also identified two putative transcription
      start points (tsp) and sequenced the 5'-flanking region of RIL to reveal
      potential binding sites for transcriptional factors.

PMID- 9573375
TI  - 3,4-Diaminopyridine-induced impairment in frog motor nerve terminal response to
      high frequency stimulation.
AB  - The refractory period of the presynaptic Na+ current (INa) of the frog
      neuromuscular junction before and after the block of the presynaptic delayed
      rectifier K+ conductance by 3,4-diaminopyridine (3,4-DAP) was studied by the
      perineurial recording technique. Application of 3,4-DAP 0.45 mM greatly prolonged
      the refractory period of the last nodes of Ranvier of frog motor axons.
      Suppression of the repetitive activity caused by 3,4-DAP by 3-aminobenzoic acid
      ethyl ester (tricaine) 0.46 mM (a local anesthetic) decreased the refractory
      period back towards normal values. These results indicate that 3,4-DAP impairs
      conduction of high frequency nerve impulses along the last nodes of Ranvier due
      to its block of presynaptic K+ conductance. The spontaneous activation of the
      most excitable, last nerve segments seemed to be the main factor causing such
      impairment. This phenomenon could explain in part the adverse motor effects shown
      by some patients treated with high doses of 3,4-DAP.

PMID- 9573376
TI  - Acute cold stress leading to elevated corticosterone neither enhances synaptic
      efficacy nor impairs LTP in the dentate gyrus of freely moving rats.
AB  - Exposure to stress has previously been found to impair long-term potentiation
      (LTP) in the hippocampus. Exposure to stress has also been proposed to induce an
      LTP-like effect. We examined the effect of acute cold stress on synaptic
      transmission, neuronal excitability, and LTP induction in the medial perforant
      path-granule cell synapse of freely moving rats. After obtaining baseline
      recordings of evoked field potentials at room temperature (23 degrees C), rats
      were transferred to an environmental cage maintained at 4 degrees C (cold group)
      or 23 degrees C (control group) and, 90 min later, high-frequency stimulation
      (HFS) was applied to the medial perforant path. Serum corticosterone measured in
      trunk blood from rats without implanted electrodes was significantly elevated in
      cold exposed (28. 7 microg/dl) rats relative to control (6.6 microg/dl). Despite
      increased corticosterone levels indicative of stress activation, cold exposed
      rats exhibited LTP of the fEPSP slope and population spike of similar magnitude
      and time course as controls. In addition, there was no stress-specific effect on
      the fEPSP slope or population spike and no effect on paired-pulse plasticity.
      Surprisingly, despite extensive cage acclimation, transferring rats to the
      environmental cage was associated with a reduction in population spike amplitude
      and an enhancement in paired-pulse facilitation. The results show that acute cold
      stress leading to elevated serum corticosterone levels neither induces LTP-like
      increases in synaptic efficacy nor impairs tetanus-evoked LTP in the dentate
      gyrus of freely moving rats. Thus, impaired working memory during cold stress is
      not due to an inability of perforant path synapses to express LTP.

PMID- 9573377
TI  - The sex-peptide gene (Acp70A) is duplicated in Drosophila subobscura.
AB  - A 3.1-kb region of Drosphila subobscura homologous to the Acp70A region of D.
      melanogaster, which contains the sex-peptide gene, was cloned and sequenced. This
      region contains an approximately 600-bp duplication that includes the sex-peptide
      and its 5' and 3' flanking regions. The preproteins are 54 and 56 amino acids
      long, respectively (as compared to 55 amino acids in D. melanogaster), and each
      includes a 19-amino-acid-long signal peptide. The C-terminal part of the mature
      peptide is highly conserved between D. melanogaster and the two copies of D.
      subobscura. In this species, both copies of the gene are transcribed and, like in
      D. melangaster, only expressed in males. The duplicated region includes 300 bp
      upstream of the gene that would therefore seem sufficient for their expression in
      males. This region presents at its 5' end a stretch 93-bp that has a high
      similarity with the corresponding region of D. melanogaster and could be part of
      a still unidentified regulatory element of these genes.

PMID- 9573378
TI  - A novel snoRNA (U73) is encoded within the introns of the human and mouse
      ribosomal protein S3a genes.
AB  - The mouse ribosomal protein S3a-encoding gene (mRPS3a) was cloned and sequenced
      in this study. mRPS3a shares identical exon/intron structure with its human
      counterpart. Both genes are split to six exons and exhibit remarkable
      conservation of the promoter region (68.8% identity in the 250 bp upstream of cap
      site) and coding region (the proteins differ in two amino acids). mRPS3a displays
      many features common to other r-protein genes, including the CpG-island at 5'-end
      of the gene, cap site within an oligopyrimidine tract and no consensus TATA or
      CAAT boxes. However, mRPS3a represents a rare subclass of r-protein genes that
      possess a long coding sequence in the first exon. Comparison of human and mouse
      S3a genes revealed sequence fragments with striking similarity within introns 3
      and 4. Here we demonstrate that these sequences encode for a novel small
      nucleolar RNA (snoRNA) designated U73. U73 contains C, D and D' boxes and a 12
      nucleotide antisense complementarity to the 28S ribosomal RNA. These features
      place U73 into the family of intron-encoded antisense snoRNAs that guide site
      specific 2'-O-ribose methylation of pre-rRNA. We propose that U73 is involved in
      methylation of the G1739 residue of the human 28S rRNA. In addition, we present
      the mapping of human ribosomal protein S3a gene (hRPS3a) and internally nested
      U73 gene to the human chromosome 4q31.2-3.

PMID- 9573379
TI  - Fos expression in rat pontine tegmental neurons following activation of the
      medial preoptic area.
AB  - Fos immunohistochemistry was used to map the distribution of pontine neurons
      excited by activation of the medial preoptic area (MPO). Although we have
      previously shown that Barrington's nucleus receives a very dense focal input from
      the MPO, electrical stimulation of the preoptic area unexpectedly induced very
      little Fos expression in Barrington's neurons. These results suggest that the MPO
      ->Barrington's projection utilizes a transmitter(s) that does not involve
      transduction of the Fos protein; alternatively, MPO afferents to Barrington's
      nucleus may be inhibitory in nature. As Barrington's nucleus plays a critical
      role in micturition, MPO projections to Barrington's nucleus may regulate voiding
      reflexes during sexual behavior. Interestingly, while the locus coeruleus (LC)
      proper receives only a sparse projection from the MPO, extensive Fos expression
      was present in LC. The finding of Fos immunoreactive LC neurons suggests that the
      excitatory influence of MPO may regulate LC neuronal activity and NE release
      during reproductive behaviors.

PMID- 9573380
TI  - Physostigmine and acetylcholine differentially activate nicotinic receptor
      subpopulations in Locusta migratoria neurons.
AB  - The effects of acetylcholine (ACh) and physostigmine (PHY) on thoracic ganglion
      neurons of Locusta migratoria were investigated using whole-cell and cell
      attached voltage clamp. ACh activated whole-cell currents with variable
      amplitudes, time course and ion channel block between cells, suggesting
      differential expression of nicotinic acetylcholine receptor (nAChR) subtypes.
      This was supported by selective block of the peak of the currents by the alpha7
      specific alpha-conotoxin ImI. PHY at 100 microM evoked smaller whole-cell
      currents with variable amplitudes and marginal desensitization. The PHY/ACh
      amplitude ratio varied between cells, and was positively related to the time
      constant of decay of the ACh response. EC50 values for the peak amplitude of the
      ACh- and PHY-induced currents were 50 microM and 3 microM, respectively. Both
      agonists activated nAChR, indicated by equal voltage-dependence and reversal
      potentials and the same pharmacological properties of ACh and PHY responses. In
      addition, PHY and ACh induced ion channel block. Co-application and cross
      desensitization experiments showed that ACh and PHY activate the same nAChR
      subpopulations. Both agonists activated nicotinic single channels with three
      conductance levels, which were equal for ACh and PHY, indicating activation of
      the same nAChR subtypes by both agonists. However, for all levels PHY displayed a
      lower open probability than ACh. Taken together, different whole-cell responses
      appear to originate from differential activation, desensitization and ion channel
      block by ACh and PHY of distinct nAChR populations.

PMID- 9573381
TI  - The genomic structure of the chicken ICSBP gene and its transcriptional
      regulation by chicken interferon.
AB  - The chicken interferon consensus sequence binding protein (ChICSBP) gene spans
      over 9 kb of DNA and consists, as its murine homolog, of nine exons. The first
      untranslated exon was identified by 5'-RACE technology. The second exon contains
      the translation initiation codon. Canonical consensus splice sites are found on
      every exon/intron junction. The introns are generally smaller than their
      mammalian counterparts. The ChICSBP and ChIRF-1 genes have been mapped by
      fluorescence in situ hybridization to different microchromosomes. The
      transcription start site has been mapped by primer extension. Inspection of the
      DNA sequence of a genomic clone containing the first exon and the region 1700-bp
      upstream revealed several potential cisregulatory elements of transcription. The
      ChICSBP mRNA is induced by recombinant ChIFN type I and ChIFN-gamma. A
      palindromic IFN regulatory element (pIRE) with high sequence homology to gamma
      activation site (GAS) sequences was functionally required in transient
      transfection assays for the induction of transcription by ChIFN-gamma.

PMID- 9573382
TI  - Suppression by topiramate of epileptiform burst discharges in hippocampal CA3
      neurons of spontaneously epileptic rat in vitro.
AB  - Topiramate, a novel antiepileptic drug, inhibits the seizures of spontaneously
      epileptic rat (SER), a double mutant (zi/zi, tm/tm) which exhibits both tonic
      convulsion and absence-like seizures from the age of 8-weeks. Hippocampal CA3
      pyramidal neurons in SER show a long-lasting depolarization shift with
      accompanying repetitive firing when a single electrostimulation is delivered to
      the mossy fibers in vitro. The effects of topiramate on the excitability of CA3
      pyramidal neurons in SER were examined to elucidate the mechanism underlying the
      antiepileptic action. Intracellular recordings were performed in 23 hippocampal
      slice preparations of 16 SER aged 8-17 weeks. Topiramate (10-100 microM) dose
      dependently inhibited the depolarizing shifts with repetitive firing induced by
      mossy fiber stimulation without affecting the first spike and resting membrane
      potentials in hippocampal CA3 neurons of SER. Higher dose of topiramate (100
      microM) sometimes inhibited the first spike, and decreased excitatory
      postsynaptic potentials in the SER CA3 neurons. However, topiramate up to 100
      microM did not affect the single action potential elicited by the stimulation in
      the hippocampal CA3 neurons of age-matched Wistar rat devoid of the seizure.
      Application of topiramate (100 microM) did not significantly affect the firing
      induced by depolarizing pulse applied in the CA3 neurons of the SER. In addition,
      topiramate (100 microM) had no effects on the Ca2+ spike induced by
      intracellularly applied depolarizing pulse in the presence of tetrodotoxin and
      tetraethylammonium. In contrast, a dose-dependent inhibition of depolarization
      and repetitive firing induced by bath application of glutamate in CA3 pyramidal
      neurons was obtained with topiramate (10-100 microM). Furthermore, topiramate
      (100 microM) decreased the number of miniature postsynaptic potential of CA3
      pyramidal neurons of SER. In patch clamp whole cell recording using acutely
      dissociated hippocampal CA3 neurons from SER aged 8-weeks and age-matched normal
      Wistar rats, there were no remarkable effects on voltage dependent Ca2+ current
      with topiramate up to 300 microM in either animal; the current was completely
      blocked by Cd2+ at a concentration of 1 mM. These findings suggest that
      topiramate inhibits release of glutamate from the nerve terminals and/or abnormal
      firing of the CA3 pyramidal neurons of SER by mainly blocking glutamate receptors
      in the neurons.

PMID- 9573383
TI  - Two types of differentially photo-regulated nuclear genes that encode sigma
      factors for chloroplast RNA polymerase in the red alga Cyanidium caldarium strain
      RK-1.
AB  - A nuclear gene, sigA, that encodes a sigma factor for chloroplast RNA polymerase
      has previously been identified and characterized in the primitive red alga
      Cyanidium caldarium strain RK-1. Southern hybridization analysis indicated the
      presence of two additional sigma factor genes, which have now been cloned and
      shown to encode virtually identical proteins that are homologous to eubacterial
      sigma factors. These genes, which are also present in the nuclear genome, have
      therefore been named sigB and sigC. The substantial sequence similarity of sigB
      and sigC to sigA of the same strain as well as to cyanobacterial principal sigma
      factors and other chloroplast sigma factors strongly suggests that the nuclear
      genome of C. caldarium contains three genes that encode two types of chloroplast
      sigma factors. Each of the three recombinant Sig proteins showed sigma factor
      activity in vitro when combined with the Escherichia coli RNA polymerase core
      enzyme. Northern blot analysis revealed that, whereas the overall abundance of
      sigA transcripts was not affected by light, the amount of sigB and sigC mRNAs was
      greater in the light than in the dark. Thus, multiple sigma factors appear to
      contribute to light-regulated gene expression in the chloroplast.

PMID- 9573384
TI  - Diurnal rhythms in ornithine decarboxylase activity and norepinephrine and
      acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged
      rats during Freund's adjuvant-induced arthritis.
AB  - Aging has been associated with attenuation of amplitude and changes in period of
      many circadian rhythms. The present study was carried out to examine, in young
      (50 days old) and old (18 months old) rats, whether 24-h rhythms of cell
      proliferation (as assessed by measuring ornithine decarboxylase activity) and of
      presynaptic adrenergic and cholinergic markers change in lymph nodes and spleen
      during Freund's adjuvant-induced arthritis. Groups of young and old Sprague
      Dawley rats were studied the day before, and on days 6, 12 and 18 after Freund's
      adjuvant injection. On day 16 after adjuvant injection, inflammation of hind
      paws, mainly in the ankle joints, was less marked in old than in young rats.
      Lymph node and splenic ornithine decarboxylase activity exhibited significant 24
      h variations with maximal activity during daily hours. Before treatment, enzyme
      activity values were significantly lower in old rats in both tissues examined.
      During the immune reaction, lymph node and splenic ornithine decarboxylase
      augmented 8-10-fold, with progressively smaller amplitude of daily variations as
      arthritis developed. In every case, mesor and amplitude of ornithine
      decarboxylase activity were lowest in old rats. Submaxillary lymph node and
      splenic tyrosine hydroxylase activity attained maximal values at night. At every
      time interval after mycobacterium adjuvant injection, amplitude and mesor of
      tyrosine hydroxylase activity rhythm were lowest in old rats. A maximum in
      submaxillary lymph node 3H-acetylcholine synthesis occurred at the afternoon. On
      day 6 and 12 after Freund's adjuvant injection, lymph node 3H-acetylcholine
      synthesis was significantly smaller in old rats. Day-night differences in
      submaxillary lymph node or splenic ornithine decarboxylase and tyrosine
      hydroxylase activities, or in submaxillary lymph node 3H-acetylcholine synthesis,
      of rats treated with the adjuvant's vehicle, did not differ significantly from
      those seen in untreated controls. The results are compatible with an age
      dependent decline of immune-mediated inflammatory responses. The activity of the
      central circadian oscillator, driven to the organs in part via the autonomic
      nervous system, seems also to deteriorate during aging.

PMID- 9573385
TI  - The gene structure and promoter analysis of mouse lymphocyte signal transduction
      molecule alpha 4 that is related to the yeast TAP42 involved in a rapamycin
      sensitive pathway.
AB  - The mouse alpha 4 phosphoprotein encoding a component associated with the B cell
      antigen receptor (BCR)-mediated signal transduction is suggested to be involved
      in a unique rapamycin-sensitive pathway. We studied the structure and the
      molecular mechanism of the expression of alpha 4 gene by isolating two phage
      clones, named #10 and #23, covering entire exons of the mouse alpha 4 gene. The
      alpha 4 gene is located within about 25 kb and composed of six exons. To analyze
      the regulation of alpha 4 gene expression, we determined the nucleotide sequence
      toward 2 kb upstream of the translation start site of the alpha 4 gene. The 5'
      flanking region does not contain a typical TATA box or the initiation consensus
      sequence, but it contains a CCAAT box, E-boxes, and several DNA binding motifs
      such as c-Myc, c-Myb, and c-Ets. Transcription of the alpha 4 gene starts at four
      different sites, determined by primer extension analysis, that were surrounded by
      Y-rich sequences. We further characterized the functional promoter of the alpha 4
      gene at the region between -263 and the transcription start site of alpha 4 gene
      by luciferase assay system and suggested that the 5' upstream region of alpha 4
      gene contains the silencer element of MT repetitive sequence.

PMID- 9573386
TI  - Methylazoxymethanol acetate-induced abnormalities in the entorhinal cortex of the
      rat; parallels with morphological findings in schizophrenia.
AB  - It has been suggested repeatedly that the non-heritable factors in the
      pathogenesis of schizophrenia involve abnormalities of prenatal neurodevelopment.
      Furthermore, post-mortem studies show neuropathology of apparently developmental
      origin in the entorhinal cortex and other brain regions of schizophrenic
      subjects. In an attempt to model a developmental defect of the entorhinal region
      in the rat, cerebrocortical proliferation was briefly interrupted during its
      earliest stages, when the entorhinal area is thought to undergo major cell
      division. Specifically, the experimental set-up involved the administration of
      methylazoxymethanol acetate (MAM) on 1 of 4 consecutive days of embryonal
      development, from E9 to E12. Analysis of the forebrain in adult animals shows
      reduction of the entorhinal cortex in rats treated on each of these days. This
      effect shifts from lateral to medial divisions of the entorhinal cortex with
      later administration of MAM, following a known developmental gradient.
      Morphological consequences of MAM administration appear to be largely confined to
      the entorhinal cortex in the groups treated on E9 to E11, although slight
      reductions of the frontal and occipital neocortex were also observed in these
      animals. MAM treatment on E12 produces relatively more widespread damage, as
      reflected among other in a small reduction of brain weight. The described brain
      abnormalities are not accompanied by obvious phenotypical changes in any, but the
      E12-treated group. They, moreover, involve cortical thinning, disorganised
      cortical layering, and abnormal temporal asymmetries. These finding bare some
      similarity to observations in brains of schizophrenic subjects. The possible
      relevance of this approach in modeling neurodevelopmental aspects of
      schizophrenia is discussed.

PMID- 9573387
TI  - Identification of a novel c-DNA overexpressed in Fanconi's anemia fibroblasts
      partially homologous to a putative L-3-phosphoserine-phosphatase.
AB  - We applied the cDNA differential display technique (DDT) in a DNA-repair
      deficient cell model to isolate genes involved in dysregulation of cell
      proliferation and development of cancer. The comparative analysis of mRNA
      expression patterns of human diploid fibroblasts from Fanconi's amemia (FA) and
      normal phenotype led to the identification of a novel cDNA CO9. Northern blot
      analysis reveals that CO9 is significantly upregulated in FA fibroblasts but
      downregulated or absent in fibroblasts from normal donors. CO9 was also highly
      expressed in FA B-cells of complementation group A and in Raji cells. However,
      CO9 is not expressed in FA complementation groups B, C, D and E. The full-length
      cDNA is 840 bp long and contains an open reading frame of 216 bp (72 amino
      acids), which encodes for a 7.6-kDa protein. The lengths of the 5' and 3'
      untranslated region are 165 and 459 bp, respectively. The N-terminal and C
      terminal nucleotide sequence of CO9 shows homology to a putative human L-3
      phosphoserine phosphatase identified recently (HSPSPASE, EMBL Accession No.
      Y10275) but lacks a 476-bp stretch in the open reading frame. The loss of
      nucleotides within the open reading frame introduces a new termination codon in
      the CO9 cDNA along with a novel COOH terminus resulting in a new protein product.
      Database chromosome mapping localized CO9 to chromosome 7q 11.2. We hypothesize
      that CO9 represents a novel protein being a partial homologue to the L-3
      phosphoserine phosphatase but with a different regulatory cell function.

PMID- 9573388
TI  - Characterization of an unusual sensor gene (virA) of Agrobacterium.
AB  - Previous studies have shown that the virulence(vir) genes of Agrobacterium
      tumefaciens strain KU12 are induced by a unique set of phenolic compounds that
      are non-functional in most strains of Agrobacterium. Further, strain KU12 is not
      induced by phenolic compounds that induce the vir genes in other strains.
      Previous studies have shown that these differences in inducing activity result
      from differences in the sensor protein for these signal molecules, the VirA
      protein. To gain some understanding of the basis for these differences in sensing
      ability, we sequenced the entire virA locus of pTiKU12, including its promoter
      region and compared this sequence with five different published virA sequences
      that respond in different ways to inducing compounds. The virA gene of KU12 is
      composed of an open single reading frame coding for 851 aa. At the aa level, the
      VirA protein of pTiKU12 is 45, 45, 49, 49 and 64% identical to the VirA proteins
      from pTiA6, pTi15955, pRiA4, pTiC58 and pTiAg162, respectively. The transcription
      start sites of pTiKU12 and pTiA6 virA genes differ significantly when mapped by
      primer extension. Unlike all other vir genes, except the virA gene of pTiAg162,
      pTiKU12 virA is constitutively expressed, and its synthesis is not induced by
      phenolic compounds. The lack of induction is accounted for by the fact that the
      promoter region does not have the conserved VirG-binding dodecadeoxynucleotide
      sequence (vir-box) that was previously identified in all promoter regions of
      inducible vir genes.

PMID- 9573389
TI  - Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer's
      disease-affected brain.
AB  - Presenilin-1 (PS-1) has been identified as the protein encoded by the chromosome
      14 locus that, when mutated, leads to familial Alzheimer's disease (FAD). The
      role PS-1 plays in the pathogenesis of Alzheimer's disease (AD) remains unclear.
      Using a set of antibodies raised against PS-1 synthetic peptides, polyclonal
      antibody to amyloid beta protein (Abeta) and end-specific antibodies against
      Abeta40, and Abeta42, immunohistochemical studies were performed on brain
      sections obtained from AD cases and controls. The PS-1 antibodies clearly stained
      amyloid angiopathies in AD-affected brains, but no recognizable immunoreactions
      were observed in any other vessels free from amyloid involvement in either AD
      affected brains or controls. Abeta antibodies and the end-specific antibody
      against Abeta40 also decorated amyloid angiopathies, showing localization similar
      to that of PS-1. Western blot analyses predominantly detected protein band
      polypeptide species of a 50 kDa, band, presumably full-length PS-1 protein with N
      terminus antisera, since these antibodies turned out to recognize a 50-kDa full
      length band in cell lysate of transfected HeLa cell overexpressing PS-1. In
      addition, we recognized 30, 27 and 25 kDa proteins in both AD and control brain
      homogenate with these antibodies. In microvessel fractions extracted from brain
      homogenates, the 50, and 27 kDa fragments were observed in AD-affected brains but
      not in those of controls. C-terminus rabbit antisera reacted strongly with the 33
      and 27 kDa bands, and additionally detected a small amount of full-length PS-1
      protein in extracts from AD and control brains. Our present data indicate that PS
      1 might be involved in the pathogenesis of amyloid angiopathy in the AD brain.

PMID- 9573390
TI  - Molecular cloning, characterization and alternative splicing of the human
      cytoplasmic serine hydroxymethyltransferase gene.
AB  - The human cytoplasmic serine hydroxymethyltransferase (CSHMT) gene was isolated,
      sequenced and its expression characterized in human MCF-7 mammary carcinoma and
      SH_5Y5Y neuroblastoma cells. The 23-kb gene contains 12 introns and 13 exons; all
      splice junctions conform to the gt/ag rule. The open reading frame is interrupted
      by 10 introns, two of which are positionally conserved within the human
      mitochondrial SHMT gene. The gene is expressed with 330 nucleotides of 5'
      untranslated message within three exons. The 5' promoter region does not contain
      a consensus TATA, and primer extension and 5'-RACE studies suggest that
      transcription initiation occurs at multiple sites. Consensus motifs for several
      regulatory proteins, including SP1, mammary and neuronal-specific elements, NF1,
      a Y-box, and two steroid hormone response elements, are present within the first
      408 nucleotides of the 5' promoter region. The human gene is expressed as
      multiple splice variants in both the 5' untranslated region and within the open
      reading frame, all due to exon excision. The splicing pattern is cell-specific.
      At least six CSHMT mRNA splice forms are present in MCF-7 cells; the gene is
      expressed as a full-length message as well as splice forms that lack exon(s) 2, 9
      and 10. In 5Y cells, the predominant form of the message lacks exon 2, which
      encodes part of the 5' untranslated region, but does not contain deletions within
      the open reading frame. Western analysis suggests that the CSHMT gene is
      expressed as a single full-length protein in 5Y cells, but as multiple forms in
      MCF-7 cells. Multiple tissue Northern blots suggest that the CSHMT message levels
      and alternative splicing patterns display tissue-specific variations.

PMID- 9573391
TI  - The trophic requirements of mature motoneurons.
AB  - Mature motoneurons interact with many cell types, including skeletal muscle
      fibres, Schwann cells, glia and various neurons. Each of these cell types is
      thought to provide trophic support to motoneurons, but it is not known whether
      the support provided by one cell type can fully substitute for the absence of a
      signal from another cell type. The ability of various growth factors to support
      motoneurons in the absence of muscle fibres, Schwann cells or long-axon synaptic
      input has been studied using in vivo models. However, these studies do not define
      the total needs of motoneurons, as local spinal influences have not been removed.
      In this paper, the total trophic requirement of mature motoneurons was assessed
      by culturing them at a low cell density, in the absence of all other cell types.
      Under these conditions, mature motoneurons die by apoptosis within 24 h, which is
      equivalent to the rate at which immature motoneurons die in vitro. This is
      consistent with the emerging view that mature cells are primed for apoptosis.
      Nine putative trophic factors (BDNF, CNTF, FGF2, GDNF, IGF I, IGF II, NT3, NT4,
      TGF-beta2), either alone or in combination, were unable to prevent the rapid
      death of the cultured motoneurons, even though some of these factors are able to
      attenuate the affects of less severe injuries such as axotomy or avulsion. The
      survival of mature motoneurons may therefore be dependent on a combination of
      growth factors, with at least one of the factors being distinct from the above
      mentioned factors.

PMID- 9573392
TI  - Glial and neuronal localization of neuronal nitric oxide synthase
      immunoreactivity in the median eminence of female rats.
AB  - Localization of neuronal nitric oxide synthase-immunoreactivity (nNOS-IR) in the
      median eminence of female rats (n=4) was examined by electron microscopy to
      explore the possibility that nitric oxide is involved in the terminal regulation
      of neurosecretory peptides such as GnRH. Under light microscopy, a dense
      distribution of nNOS-IR was observed in this region. Electronmicroscopically,
      nNOS-IR was found in glial elements and nerve terminals containing dense-core
      vesicles. We also found a few nNOS-immunopositive synapses, in which intense
      immunoreactivity was found on the postsynaptic density and mitochondrial
      membrane. The localization of nNOS-IR in nerve terminals and glial elements in
      the median eminence might indicate that nNOS plays a role in regulating the
      release of neurosecretory peptide.

PMID- 9573393
TI  - Analysis of the genomic organisation of a small chromosome of Leishmania
      braziliensis M2903 reveals two genes encoding GTP-binding proteins, one of which
      belongs to a new G-protein family and is an antigen.
AB  - Leishmania braziliensis M2903 contains a highly amplified small chromosome. This
      work is aimed at resolving its structural organization and determining whether
      this unusual chromosome contains specific genes encoding proteins with important
      functions in disease pathology or drug resistance. Our results show that the
      M2903 250-kb small chromosome contains LD1 sequences and has an inverted repeat
      structure. The LD1 sequences and two cDNAs (cDNA2 and cDNA53) were mapped on a
      cosmid contig, and the two cDNAs and the corresponding genomic fragments from the
      small chromosome were sequenced. The gene encoding cDNA2 predicts a putative GTP
      binding protein with homology to other GTP-binding proteins only in the G-1
      domain region; however, four other conserved motifs can be recognized. Sequence
      similarity to cDNA53 is located in at least five chromosomes, and its small
      chromosome copy is a pseudogene. An open reading frame downstream of the cDNA53
      pseudogene predicts another GTP-binding protein that belongs to a new G-protein
      family with an unusual conserved GTP-binding domain and a newly characterized
      conserved sequence motif. A portion of this GTP-binding protein gene was studied
      previously in L. aethiopica as a recombinant antigen that reacts with human
      antibodies.

PMID- 9573394
TI  - Effects of testosterone and progesterone on brain 5alpha-reductase and aromatase
      in Long-Evans males and comparison of aromatase in Long-Evans vs. Sprague-Dawley
      rats.
AB  - We investigated medial basal hypothalamic-preoptic area (MBH-POA) 5alpha
      reductase and aromatase enzyme activities in gonadally intact and castrated adult
      Long-Evans (L-E) male rats treated with testosterone (T), progesterone (P), and a
      combination of T+P. MBH-POA 5alpha-reductase and aromatase activities did not
      differ significantly among the groups. The lack of a difference in MBH-POA
      aromatase between control and castrated L-E animals was unexpected. In two
      further experiments, MBH-POA aromatase was examined in intact and castrated L-E
      and Sprague-Dawley (S-D) rats, using direct and indirect assays. The activity in
      castrated S-D (but again, not in L-E) rats significantly decreased compared to
      control values. These data suggest that the absence of gonads does not decrease
      MBH-POA aromatase in adult L-E rats.

PMID- 9573395
TI  - Placement in a novel environment induces fos-like immunoreactivity in
      supramammillary cells projecting to the hippocampus and midbrain.
AB  - Injections of fluorescent retrograde tracers into either the hippocampal
      formation or the midbrain raphe nuclei resulted in retrograde labeling of many
      cells in the supramammillary region of the hypothalamus. Double labeling studies
      indicated that these two projections originate from different populations of
      supramammillary cells. Expression of the proto-oncoprotein Fos could be induced
      in some retrogradely labeled cells by placing rats in a novel open field before
      sacrifice. Although seen in both cell types, Fos-like immunoreactivity was
      significantly more common in supramammillary cells projecting to the hippocampus
      than in those projecting to the midbrain. These findings suggest that the
      supramammillary region may contain several populations of neurons which are
      differentially responsive to certain behavioral manipulations.

PMID- 9573396
TI  - Stimulation of RNA 3' processing by flanking DNA in Xenopus oocytes.
AB  - We have previously shown that the second poly(A) signal of the Xenopus laevis
      alpha-tubulin gene X alpha T14, which contains the rare hexanucleotide CAUAAA,
      requires a surprisingly large amount of 3' flanking DNA to be used efficiently in
      Xenopus oocytes. To investigate the nature of the interaction between the X alpha
      T14 3' flank and upstream 3' processing sites, we have developed a modified
      oocyte assay based on the stimulation of processing at a single poly(A) signal.
      We mutated both the hexanucleotide and GU/U-rich components of a strong synthetic
      poly(A) signal (SPA) in order to weaken it severely. We found that efficient use
      of the mutant signal could be fully restored by the addition of 1.2 kb of X alpha
      T14 3' flank, but only in its natural orientation. Functional dissection of the X
      alpha T14 3' flank defined two separate regions that were each capable of
      partially restoring processing efficiency, presumably because they contain
      multiple, relatively weak processing enhancers. We discuss how the stimulation of
      3' processing by flanking regions in oocytes could be explained by mechanisms
      that operate on the processing machinery directly or by indirect effects mediated
      by transcriptional pausing.

PMID- 9573397
TI  - Homosynaptic long-term depression of CA3-CA3 synapses in the in vivo hippocampus.
AB  - We tested the hypothesis that homosynaptic long-term depression (LTD) can be
      induced at the CA3-CA3 synapses in the adult, in vivo hippocampus while the CA3
      CA1 synapses remain unchanged. Low-frequency conditioning stimulation of the
      contralateral fimbria significantly depressed the CA3 population response but did
      not change the simultaneously recorded CA3 response to angular bundle test
      stimulation. Similarly, in another group of animals, low-frequency conditioning
      stimulation of the contralateral fimbria depressed the CA3 synaptic response and
      left the collateral CA1 synaptic response unchanged. Among the possible
      explanations for this differential induction of homosynaptic LTD at the CA3-CA3
      and CA3-CA1 synapses are differential control of intracellular calcium, differing
      levels of inhibition in these two regions, and the recency of 'natural' long-term
      potentiation in the two regions.

PMID- 9573398
TI  - Serotonin-induced population primary afferent depolarisation in vitro: the
      effects of neonatal capsaicin treatment.
AB  - The effect of 5-hydroxytryptamine (5-HT) on population primary afferent
      depolarisation (PAD) has been studied using in vitro spinal cord preparations
      from normal and capsaicin pre-treated (neonatal subcutaneous injection; 75 mg kg
      1) rats aged 10-14 days. In preparations from untreated rats, the concentration
      response curve for PAD in response to 0.1-100 microM 5-HT was bell-shaped but in
      the capsaicin pre-treated group, a non-saturating 5-HT-induced PAD concentration
      response curve was generated. Quantitatively, the mean PAD responses to 0.1-10
      microM 5-HT were of a greater amplitude in the control group compared to the
      capsaicin pre-treated group (p</=0. 05). For the highest 5-HT concentration of
      100 microM, PAD values were significantly greater in the capsaicin pre-treated
      group (p</=0. 05). These data indicate that control of sensory afferent polarity
      may involve two 5-HT receptor types and that nociceptive and non-nociceptive
      afferents may be targets for released 5-HT.

PMID- 9573399
TI  - Effects of estrogen replacement on choline acetyltransferase and trkA mRNA
      expression in the basal forebrain of aged rats.
AB  - The effects of one week of estrogen replacement on choline acetyltransferase
      (ChAT) and trkA mRNA expression are examined in young and aged rodents to
      determine whether estrogen continues to affect cholinergic neurons in aging
      brain. Significant increases in ChAT and trkA are observed in the nucleus basalis
      of Meynert (nBM) of both age groups. ChAT expression is also increased in the HDB
      without changes in trkA expression. Results indicate modulation of ChAT
      expression by estrogen is retained in the aged rodent brain and suggests the
      possibility that changes in ChAT expression may be dissociated from concurrent
      alterations in trkA.

PMID- 9573401
TI  - Neurodegeneration induced by reversed microdialysis of NMDA; a quantitative model
      for excitotoxicity in vivo.
AB  - This study characterizes a quantifiable in vivo model of excitotoxicity. In
      halothane anesthetized rats, microdialysis probe was implanted into somatosensory
      cortex/striatum and perfused by various concentrations (1, 10, 50 and 100 mmol/l)
      of N-methyl-d-aspartate (NMDA) for 20 min. After 24 h, histological
      quantification confirmed that NMDA produced a concentration-dependent excitotoxic
      lesion. With 10 mmol/l NMDA, coadministration of magnesium reduced significantly,
      and 2-amino-5-phosphonovalerate blocked completely the development of excitotoxic
      injury.

PMID- 9573400
TI  - Molecular cloning and characterization of FHL2, a novel LIM domain protein
      preferentially expressed in human heart.
AB  - A full-length cDNA clone encoding a novel LIM-only protein was isolated and
      sequenced from a human fetal heart cDNA library. This full-length clone consists
      of 1416 base pairs and has a predicted open reading frame (ORF) encoding 279
      amino acids. The ORF of this polypeptide codes for the human heart-specific four
      and a half LIM-only protein 2 (FHL2). It possesses an extra zinc finger that is a
      half LIM domain and four repeats of LIM domain. When the human FHL2 cDNA probe
      was used to hybridize with poly-A RNA of various human tissues, a very strong
      signal could be seen in heart tissues, and only moderately low signals could be
      detected in placenta, skeletal muscle and ovary. Virtually no signal could be
      detected in brain, lung, liver, kidney, pancreas, spleen, thymus, prostate,
      testis, small intestine, colon or peripheral blood leukocyte. FHL2 was mapped to
      chromosome 2q12-q13 by fluorescent in-situ hybridization (FISH).

PMID- 9573402
TI  - Corrigendum to: 'Evolutionary significance of intra-genome duplications on human
      chromosomes'

PMID- 9573404
TI  - Computational models of neuromodulation.
AB  - Computational modeling of neural substrates provides an excellent theoretical
      framework for the understanding of the computational roles of neuromodulation. In
      this review, we illustrate, with a large number of modeling studies, the specific
      computations performed by neuromodulation in the context of various neural models
      of invertebrate and vertebrate preparations. We base our characterization of
      neuromodulations on their computational and functional roles rather than on
      anatomical or chemical criteria. We review the main framework in which
      neuromodulation has been studied theoretically (central pattern generation and
      oscillations, sensory processing, memory and information integration). Finally,
      we present a detailed mathematical overview of how neuromodulation has been
      implemented at the single cell and network levels in modeling studies. Overall,
      neuromodulation is found to increase and control computational complexity.

PMID- 9573403
TI  - RET-like immunostaining of spinal motoneurons in amyotrophic lateral sclerosis.
AB  - The receptor tyrosine kinase RET is part of a functional receptor for glial cell
      derived neurotrophic factor (GDNF) and neurturin (NTN) which are potent
      neurotrophic factors for motoneurons. Here, we have studied RET-like
      immunoreactivity of motoneurons in post-mortem spinal cords of patients with
      amyotrophic lateral sclerosis (ALS) and in controls. We report that the intensity
      of RET-like immunostaining of motoneurons in ALS is decreased significantly to
      81% of control values. Despite this change, the proportion of all large (>40
      micron diameter) motoneurons showing RET-like immunoreactivity in ALS remains
      high (82-85%) and is not significantly different to controls. The persistence of
      RET-like immunoreactivity in the majority of large motoneurons in ALS could be
      important in the design of clinical trials of GDNF and NTN.

PMID- 9573405
TI  - Weight-value convergence of the SOM algorithm for discrete input.
AB  - Some insights on the convergence of the weight values of the self-organizing map
      (SOM) to a stationary state in the case of discrete input are provided. The
      convergence result is obtained by applying the Robbins-Monro algorithm and is
      applicable to input-output maps of any dimension.

PMID- 9573406
TI  - Reading neuronal synchrony with depressing synapses.
AB  - A recent experiment showed that neurons in the primary auditory cortex of the
      monkey do not change their mean firing rate during an ongoing tone stimulus. The
      only change was an enhanced correlation among the individual spike trains during
      the tone. We show that there is an easy way to extract this coherence information
      in the cortical cell population by projecting the spike trains through depressing
      synapses onto a postsynaptic neuron.

PMID- 9573407
TI  - Neural networks with dynamic synapses.
AB  - Transmission across neocortical synapses depends on the frequency of presynaptic
      activity (Thomson & Deuchars, 1994). Interpyramidal synapses in layer V exhibit
      fast depression of synaptic transmission, while other types of synapses exhibit
      facilitation of transmission. To study the role of dynamic synapses in network
      computation, we propose a unified phenomenological model that allows computation
      of the postsynaptic current generated by both types of synapses when driven by an
      arbitrary pattern of action potential (AP) activity in a presynaptic population.
      Using this formalism, we analyze different regimes of synaptic transmission and
      demonstrate that dynamic synapses transmit different aspects of the presynaptic
      activity depending on the average presynaptic frequency. The model also allows
      for derivation of mean-field equations, which govern the activity of large,
      interconnected networks. We show that the dynamics of synaptic transmission
      results in complex sets of regular and irregular regimes of network activity.

PMID- 9573408
TI  - Spike frequency adaptation affects the synchronization properties of networks of
      cortical oscillations.
AB  - Oscillations in many regions of the cortex have common temporal characteristics
      with dominant frequencies centered around the 40 Hz (gamma) frequency range and
      the 5-10 Hz (theta) frequency range. Experimental results also reveal spatially
      synchronous oscillations, which are stimulus dependent (Gray & Singer, 1987;
      Gray, Konig, Engel, & Singer, 1989; Engel, Konig, Kreiter, Schillern, & Singer,
      1992). This rhythmic activity suggests that the coherence of neural populations
      is a crucial feature of cortical dynamics (Gray, 1994). Using both simulations
      and a theoretical coupled oscillator approach, we demonstrate that the spike
      frequency adaptation seen in many pyramidal cells plays a subtle but important
      role in the dynamics of cortical networks. Without adaptation, excitatory
      connections among model pyramidal cells are desynchronizing. However, the slow
      processes associated with adaptation encourage stable synchronous behavior.

PMID- 9573409
TI  - GABAergic inhibitory control of the transient and sustained components of
      orientation selectivity in a model microcolumn in layer 4 of cat visual cortex.
AB  - Recently proposed models of orientation tuning in layer 4 of cat primary visual
      cortex (Somers, Nelson, & Sur, 1995; Douglas, Koch, Mahowald, Martin, & Suarez,
      1995) rely on widespread inhibitory intracortical connections to suppress the
      nonoptimal component of a broadly tuned thalamic input, while local excitatory
      intracortical connections amplify the optimal component. However, new
      experimental data (Ferster, Chung, & Wheat, 1996) and theoretical analyses
      (Ferster, 1987; Krukowski, Priebe, & Miller, 1996) show that the temporally
      modulated component of thalamic input is well tuned and that the cortical
      circuitry must simply subtract an unmodulated DC component at nonoptimal
      orientations to obtain sharp tuning. In addition, within a single hypercolumn in
      layer 4, inhibitory and excitatory layer 4 neurons have approximately equal-sized
      axonal fields, making the most of their synapses within their own dendritic field
      (Kisvarday, Martin, Whitteridge, & Somogyi, 1985; Martin & Whitteridge, 1984). We
      have constructed a model of a single microcolumn in which GABA inhibition
      subtracts the DC and controls the sustained response, while GABA inhibition
      controls the response to transient and suprathreshold inputs. The model fits
      experimental data based on stimulation with drifting sine-wave gratings as well
      as flashed bars, explains a counterintuitive property of the GABA conductance,
      and at suboptimal orientations and submaximal contrasts produces an exponential
      distribution of firing frequencies.

PMID- 9573410
TI  - Changes in GABAB modulation during a theta cycle may be analogous to the fall of
      temperature during annealing.
AB  - Changes in GABA modulation may underlie experimentally observed changes in the
      strength of synaptic transmission at different phases of the theta rhythm (Wyble,
      Linster, & Hasselmo, 1997). Analysis demonstrates that these changes improve
      sequence disambiguation by a neural network model of CA3. We show that in the
      framework of Hopfield and Tank (1985), changes in GABA suppression correspond to
      changes in the effective temperature and the relative energy of data terms and
      constraints of an analog network. These results suggest that phasic changes in
      the activity of inhibitory interneurons during a theta cycle may produce dynamics
      that resemble annealing. These dynamics may underlie a role for the theta cycle
      in improving sequence retrieval for spatial navigation.

PMID- 9573411
TI  - RST: a connectionist architecture to deal with spatiotemporal relationships.
AB  - In the past decade, connectionism has proved its efficiency in the field of
      static pattern recognition. The next challenge is to deal with spatiotemporal
      problems. This article presents a new connectionist architecture, RST (reseau
      spatio temporel [spatio temporal network]), with such spatiotemporal capacities.
      It aims at taking into account at the architecture level both spatial
      relationships (e.g., as between neighboring pixels in an image) and temporal
      relationships (e.g., as between consecutive images in a video sequence).
      Concerning the spatial aspect, the network is embedded in actual space (two) or
      three-dimensional-, the metrics of which directly influence its structure through
      a connection distribution function. For the temporal aspect, we looked toward
      biology and used a leaky-integrator neuron model with a refractory period and
      postsynaptic potentials. The propagation of activity by spatiotemporal
      synchronized waves enables RST to perform motion detection and localization in
      sequences of video images.

PMID- 9573412
TI  - A neural model of contour integration in the primary visual cortex.
AB  - Experimental observations suggest that contour integration may take place in V1.
      However, there has yet to be a model of contour integration that uses only known
      V1 elements, operations, and connection patterns. This article introduces such a
      model, using orientation selective cells, local cortical circuits, and horizontal
      intracortical connections. The model is composed of recurrently connected
      excitatory neurons and inhibitory interneurons, receiving visual input via
      oriented receptive fields resembling those found in primary visual cortex.
      Intracortical interactions modify initial activity patterns from input,
      selectively amplifying the activities of edges that form smooth contours in the
      image. The neural activities produced by such interactions are oscillatory and
      edge segments within a contour oscillate in synchrony. It is shown analytically
      and empirically that the extent of contour enhancement and neural synchrony
      increases with the smoothness, length, and closure of contours, as observed in
      experiments on some of these phenomena. In addition, the model incorporates a
      feedback mechanism that allows higher visual centers selectively to enhance or
      suppress sensitivities to given contours, effectively segmenting one from
      another. The model makes the testable prediction that the horizontal cortical
      connections are more likely to target excitatory (or inhibitory) cells when the
      two linked cells have their preferred orientation aligned with (or orthogonal to)
      their relative receptive field center displacements.

PMID- 9573413
TI  - Predictive neural networks for learning the time course of blood glucose levels
      from the complex interaction of counterregulatory hormones.
AB  - Diabetes mellitus is a widespread disease associated with an impaired hormonal
      regulation of normal blood glucose levels. Patients with insulin-dependent
      diabetes mellitus (IDDM) who practice conventional insulin therapy are at risk of
      developing hypoglycemia (low levels of blood glucose), which can lead to severe
      dysfunction of the central nervous system. In large retrospective studies, up to
      approximately 4% of deaths of patients with IDDM have been attributed to
      hypoglycemia (Cryer, Fisher, & Shamoon, 1994; Tunbridge, 1981; Deckert, Poulson,
      & Larsen, 1978). Thus, a better understanding of the complex hormonal interaction
      preventing hypoglycemia is crucial for treatment. Experimental data from a study
      on insulin-induced hypoglycemia in healthy subjects are used to demonstrate that
      feedforward neural networks are capable of predicting the time course of blood
      glucose levels from the complex interaction of glucose counterregulatory (glucose
      raising) hormones and insulin. By simulating the deficiency of single hormonal
      factors in this regulatory network, we found that the predictive impact of
      glucagon, epinephrine, and growth hormone secretion, but not of cortisol and
      norepinephrine, were dominant in restoring normal levels of blood glucose
      following hypoglycemia.

PMID- 9573414
TI  - Properties of support vector machines.
AB  - Support vector machines (SVMs) perform pattern recognition between two point
      classes by finding a decision surface determined by certain points of the
      training set, termed support vectors (SV). This surface, which in some feature
      space of possibly infinite dimension can be regarded as a hyperplane, is obtained
      from the solution of a problem of quadratic programming that depends on a
      regularization parameter. In this article, we study some mathematical properties
      of support vectors and show that the decision surface can be written as the sum
      of two orthogonal terms, the first depending on only the margin vectors (which
      are SVs lying on the margin), the second proportional to the regularization
      parameter. For almost all values of the parameter, this enables us to predict how
      the decision surface varies for small parameter changes. In the special but
      important case of feature space of finite dimension m, we also show that m + 1
      SVs are usually sufficient to determine the decision surface fully. For
      relatively small m, this latter result leads to a consistent reduction of the SV
      number.

PMID- 9573415
TI  - Validation of voting committees.
AB  - This article contains a method to bound the test errors of voting committees with
      members chosen from a pool of trained classifiers. There are so many prospective
      committees that validating them directly does not achieve useful error bounds.
      Because there are fewer classifiers than prospective committees, it is better to
      validate the classifiers individually than use linear programming to infer
      committee error bounds. We test the method using credit card data. Also, we
      extend the method to infer bounds for classifiers in general.

PMID- 9573416
TI  - Toward optimally distributed computation.
AB  - This article introduces the concept of optimally distributed computation in
      feedforward neural networks via regularization of weight saliency. By
      constraining the relative importance of the parameters, computation can be
      distributed thinly and evenly throughout the network. We propose that this will
      have beneficial effects on fault-tolerance performance and generalization ability
      in large network architectures. These theoretical predictions are verified by
      simulation experiments on two problems: one artificial and the other a real-world
      task. In summary, this article presents regularization terms for distributing
      neural computation optimally.

PMID- 9573417
TI  - Efficient adaptive learning for classification tasks with binary units.
AB  - This article presents a new incremental learning algorithm for classification
      tasks, called NetLines, which is well adapted for both binary and real-valued
      input patterns. It generates small, compact feedforward neural networks with one
      hidden layer of binary units and binary output units. A convergence theorem
      ensures that solutions with a finite number of hidden units exist for both binary
      and real-valued input patterns. An implementation for problems with more than two
      classes, valid for any binary classifier, is proposed. The generalization error
      and the size of the resulting networks are compared to the best published results
      on well-known classification benchmarks. Early stopping is shown to decrease
      overfitting, without improving the generalization performance.

PMID- 9573418
TI  - A systematic and effective supervised learning mechanism based on Jacobian rank
      deficiency.
AB  - Most neural network applications rely on the fundamental approximation property
      of feedforward networks. Supervised learning is a means of implementing this
      approximate mapping. In a realistic problem setting, a mechanism is needed to
      devise this learning process based on available data, which encompasses choosing
      an appropriate set of parameters in order to avoid overfitting, using an
      efficient learning algorithm measured by computation and memory complexities,
      ensuring the accuracy of the training procedures as measured by the training
      error, and testing and cross-validation for generalization. We develop a
      comprehensive supervised learning algorithm to address these issues. The
      algorithm combines training and pruning into one procedure by utilizing a common
      observation of Jacobian rank deficiency in feedforward networks. The algorithm
      not only reduces the training time and overall complexity but also achieves
      training accuracy and generalization capabilities comparable to more standard
      approaches. Extensive simulation results are provided to demonstrate the
      effectiveness of the algorithm.

PMID- 9573419
TI  - Dynamic typology clustering within the stages of change for smoking cessation.
AB  - Dynamic typology clustering was employed to find homogeneous subgroups of smokers
      within each of three early stages of change (precontemplation, contemplation,
      preparation) in a representative sample of smokers. Individual change profiles
      were created by coding the stage of change for each subject at five consecutive
      assessment points over a 2-year period (baseline and 6, 12, 18, and 24 months). A
      total of 446 unique change profiles were found in the sample of 2,088 smokers who
      had complete data for all five time points. The sample was initially split into
      three groups determined by baseline stage of change. Within each initial stage,
      subgroups that shared similar patterns of change were interpreted by examining
      the shape and elevation of the change profiles. Four major types of profiles
      emerged: a stable profile, a progressing profile, a vacillating profile, and a
      regressing profile. External validation revealed significant differences among
      the dynamic typology subtypes on key transtheoretical model constructs (processes
      of change, decisional balance, situational temptations). These results both
      support and complement key construct relationships within the transtheoretical
      model and can provide important predictive information to direct and enhance
      treatment interventions for smoking cessation.

PMID- 9573420
TI  - Psychological and behavioural factors associated with relapse among heroin
      abusers treated in therapeutic communities.
AB  - The authors carried out a comparative study on two groups of heroin abusers
      treated in several therapeutic communities: One group consumed heroin on at least
      three occasions between the fifth and sixth months of treatment (n = 130), and
      the other continued without consuming heroin after 7 months of treatment (n =
      130). The instruments used for data collection were a structured interview and
      urine analysis. The relapsed group includes older patients with more medical
      problems, lower educational and occupational level, and major chronicity in
      heroin consumption. The collection of retrospective data referring to the
      treatment period shows that relapsed patients more frequently consumed alcohol,
      hashish, cocaine, and amphetamines; suffered more heroin cravings; used fewer
      coping strategies to overcome the craving; and justified the craving or the
      heroin consumption in more situations than those who abstained. The last heroin
      craving during the treatment period arose in different temporal, social, and
      physical contexts in the two groups, and it was accompanied more frequently by
      inadequate responses in the relapsed group: psychophysiological alterations,
      depressed feelings, negative thoughts, and coping behaviours. The two groups are
      different in their attitudes toward heroin abstinence. The authors discuss the
      findings from a cognitive-behavioural perspective and come to the conclusion that
      various models need to be integrated.

PMID- 9573421
TI  - Eating behavior and weight control among women using smokeless tobacco,
      cigarettes, and normal controls.
AB  - Although considerable research has investigated the use of cigarette smoking for
      weight management, the potential role of smokeless tobacco (ST) use in dieting
      behavior has not been explored. Several measures designed to assess dieting
      behavior, attitudes toward eating, and tobacco use were administered to adult
      women using ST (n = 18), cigarettes (n = 20), and no tobacco (n = 20). Use of
      tobacco for weight loss was prevalent among the women smoking cigarettes. Nearly
      half the women in the cigarette-smoking group (45%) reported use of cigarettes to
      assist in weight loss, and only three (16.6%) of the women in the ST groups
      indicated use of ST for such purposes. No significant differences were observed
      across groups on measures of dietary restraint or attitudes toward eating. Issues
      of dieting and weight control may not be important factors in prompting ST use.
      Implications and areas for further research are discussed.

PMID- 9573422
TI  - Variations in psychosocial functioning associated with patterns of progression in
      cocaine-dependent men.
AB  - This study examined the relationship between patterns of progression of cocaine
      use and psychosocial functioning in a sample of cocaine-dependent men who were
      veterans. Four patterns of progression were examined: mild-severe, moderate
      severe, mild-moderate-severe, and severe only. Analysis of variance and post hoc
      analysis with Duncan grouping revealed significant differences among cocaine
      users with different patterns of progression in terms of negativism, problem
      index for situations involving unpleasant emotions, problem index for situations
      involving urges, depression, somatic anxiety, and medical problems in the family.
      However, there were no significant differences on sensation seeking, confidence
      to resist taking cocaine in different situations, obsessive compulsiveness,
      somatization, attention deficit, and social adjustment. Cocaine users with a
      severe-only pattern of progression were significantly more dysfunctional than
      those with mild-moderate-severe progression in terms of negativism, problem index
      for situations involving unpleasant emotions, depression, and somatic anxiety.
      Cocaine users with mild-moderate-severe progression had significantly less
      somatic anxiety than those with mild-severe progression and had less negativism
      and a lower problem index for urges than those with moderate-severe progression.
      Logistic regression analysis revealed unique behavioral variables associated with
      different patterns of progression. The implications of these findings for
      treatment are discussed.

PMID- 9573423
TI  - Measuring readiness and motivation to quit smoking among women in public health
      clinics: predictive validity.
AB  - We conducted an independent pilot test of the internal consistency, stability,
      and predictive validity of the instrument presented by Crittenden, Manfredi,
      Lacey, Warnecke, and Parsons (1994) using a two-wave panel of female smokers in
      12 public health clinics. This instrument subdivides the precontemplation stage
      proposed by Prochaska and DiClemente into three more distinct stages: not
      contemplating quitting or cutting down, not contemplating quitting, and not
      contemplating quitting within 6 months. Findings confirm that the instrument is
      useful for evaluating movement toward quitting for populations that are largely
      concentrated in the precontemplative stage. The concurrent and predictive
      validity of the elaborated stages and the reliability and stability of smoking
      motivation and confidence indicate that the instrument is sensitive enough to
      track changes in readiness and motivation across the full readiness continuum.

PMID- 9573424
TI  - The role of weight control as a motivation for cocaine abuse.
AB  - Heavy use of cocaine and alcohol in female cocaine abusers with eating disorders
      has been reported, but the prevalence and motivation for concurrent substance use
      has not been well investigated. This study of 37 female and 40 male cocaine
      abusers demonstrated that almost half of the women used cocaine and/or alcohol as
      a weight control measure, and 13% of the males did the same. Thirteen (72%) of 18
      females endorsing weight-related use of cocaine had a current diagnosis of an
      eating disorder. Only two males (5%) had a past history of an eating disorder.
      Eleven (85%) of those women with a current eating disorder endorsed using alcohol
      as an appetite suppressant. These findings support the need to evaluate weight
      control motivation in cocaine users and to provide specific treatment aimed at
      addressing the interaction between the eating disorder and the substance abuse
      problem.

PMID- 9573425
TI  - Individual differences in cue reactivity among smokers trying to quit: effects of
      gender and cue type.
AB  - Across studies, when presented with a variety of smoking cues, smokers and ex
      smokers evidence distinct patterns of self-reported, physiological, and
      behavioral reactions. However, few studies have compared more than two different
      kinds of cues within the same experiment. Furthermore, despite the importance of
      examining the moderating effect of gender on smoking outcomes, few studies have
      examined gender differences in smoking cue reactivity. We examined the effect of
      eight distinct cue manipulations on heart rate, mean arterial pressure, smoking
      urges, and self-efficacy in a sample of 129 participants (50% female) who had
      recently quit smoking. Cue manipulations included (a) in vivo exposure, (b) an
      idiographically designed exposure of subjects' most recent relapse, (c) an
      idiographically designed exposure to subjects' highest risk situation, and (d)
      affectively valenced standardized scripts depicting situations generally
      associated with relapse. These manipulations were compared to a standard
      cognitive stressor (mental arithmetic) and to a resting baseline. Results
      revealed differences in the degree of reactivity to different manipulations, with
      in vivo cues producing the greatest changes. Gender differences in reactivity
      between the type of cues presented were found for mean arterial pressure, with
      standardized scripts producing greater changes for women. These findings have
      implications for understanding the reasons for differences in cue reactivity
      across manipulations and for gender differences in cue reactivity.

PMID- 9573426
TI  - The applicability of the theory of planned behavior to the intention to quit
      smoking across workplaces in southern Taiwan.
AB  - An examination of the applicability of the theory of planned behavior (TPB) to
      the intention to quit smoking across workplaces was conducted. Subjects were
      randomly selected from three workplaces in southern Taiwan. Those from a large
      public steel-manufacturing company were used for model building, and those from
      two private auto-parts-manufacturing companies served to cross-validate the
      model. Eligible subjects were divided into three study samples: a learning sample
      and two test samples. Three predictors--priority of quitting, past behavior
      (measured as previous quit attempt), and habit (measured as nicotine dependence)-
      were added to the TPB model. The results of this study show that TPB based on the
      learning sample fit well in another sample from the same workplace but poorly in
      other workplaces. When priority of quitting and past behavior were added to the
      TPB model, prediction to other workplaces significantly improved. Habit had no
      significant contribution to the intention to quit in the TPB model. Detailed
      discussions of the results are provided.

PMID- 9573427
TI  - Substance abuse treatment for pregnant women: a window of opportunity?
AB  - The use of substance abuse treatment services by pregnant and nonpregnant women
      was compared to explore the effects of pregnancy on treatment utilization and
      outcomes. Treatment service records for 227 pregnant drug- and alcohol-dependent
      women and a matched comparison group of 277 nonpregnant women were retrieved from
      the Massachusetts Bureau of Substance Abuse Services Management Information
      System. Treatment services received by the two groups of women during a 6-month
      period following an index detoxification were tabulated and compared. Treatment
      services for pregnant women differed quantitatively and qualitatively from the
      services received by nonpregnant women over the 6-month time period. After
      controlling for background characteristics and substance abuse history, pregnant
      women were 1.7 times more likely to be readmitted to detoxification, 2.8 times
      more likely to enter residential facilities, and 5.4 times more likely to enter
      methadone programs. For both groups, the use of outpatient and/or residential
      treatment services following discharge from detoxification significantly reduced
      the risk of subsequent detoxification admissions. The increased likelihood of
      admission to detoxification, residential, and methadone services suggests that
      treatment programs have improved access to care for pregnant women. Multiple
      detoxification admissions suggest, however, that some pregnant women have
      difficulty entering stable recovery. Given the brevity of the gestational period
      and the detrimental effects of drug and alcohol use on fetal outcomes, the use of
      continuing treatment services for pregnant women is strongly recommended.

PMID- 9573428
TI  - Heart rate responses indicate locked-in attention in alcoholics immediately prior
      to drinking.
AB  - Twenty alcohol-dependent subjects and 10 social drinkers were tested in two
      experimental conditions: (a) when they were informed that their drinks contained
      alcohol and (b) when they were informed that their drinks were soft drinks. When
      told "alcohol," alcoholics evidenced a heart rate (HR) acceleration, whereas
      control subjects were unaffected by the instruction. Moreover, severely dependent
      (SD) alcoholics' HR remained elevated within the evaluation period whereas
      moderately dependent (MD) alcoholics' HR returned to baseline levels. The
      sustained HR acceleration in SD alcoholics suggests that their attention became
      "locked in" on the alcohol information immediately prior to drinking in the "told
      alcohol" condition. Such an inward focus of attention will seriously reduce the
      alcoholic's ability to shift attention away from alcohol information, which may
      explain the difficulties alcoholics experience in coping with high-risk
      situations for drinking. In the SD alcoholics, HR acceleration correlated with
      the time it took to start drinking subsequent beverages containing alcohol in the
      told-alcohol instruction. In the MD alcoholics, HR responses were related to the
      reported urge to drink, whereas it was only in the nondependent subjects that
      self-reported urge to drink was related to the actual alcohol-use behavior.

PMID- 9573429
TI  - The frequency and impact of violent trauma among pregnant substance abusers.
AB  - This research was conducted with 96 low-income pregnant women who enrolled in a
      residential substance abuse treatment program. The study had three goals: (a) to
      document the prevalence of exposure to violent trauma, (b) to examine the
      prevalence of posttraumatic stress symptomatology, and (c) to assess if trauma
      exposure and posttraumatic stress were related to program completion. Results
      indicated that the sample had high rates of exposure to violent trauma, as 72%
      had experienced sexual assault, 67% had experienced physical assault, and 68% had
      experienced indirect violent trauma. High rates of traumatic stress were found in
      that 62% displayed symptoms consistent with posttraumatic stress disorder.
      Finally, logistic regression analyses revealed that traumatic stress, but not
      trauma exposure, was related to program completion. Findings suggest that
      treatment providers need to assess trauma histories and traumatic stress
      symptoms.

PMID- 9573430
TI  - Smoking and cognitive deficits in schizophrenia: a pilot study.
AB  - The cross-sectional study assessed the associations among smoking status, number
      of cigarettes smoked per day, and psychiatric symptoms in 88 chronic
      schizophrenic outpatients with a stable psychic condition. Among the 49 smokers,
      the number of cigarettes smoked per day was associated with the severity of
      cognitive symptoms of the Positive and Negative Syndrome Scale. The authors
      suggest that smoking may alleviate cognitive deficits in schizophrenia by
      increasing dopaminergic neurotransmission in the prefrontal areas of the brain.

PMID- 9573431
TI  - Psychophysiological reactivity to alcohol advertising in light and moderate
      social drinkers.
AB  - Psychophysiological responses to alcohol and nonalcohol advertising slides were
      compared in light and moderate social drinkers. Each slide presentation was
      interspersed with a rest period. Before viewing the slides, participants
      completed a questionnaire to estimate their quantity and frequency of alcohol
      consumption. Participants were divided into two groups using a median split of
      alcohol consumption scores. Light social drinkers showed a significant decrease
      in heart rate response to both alcohol-related and nonalcohol advertisements.
      Moderate social drinkers showed a significant increase in skin conductance to
      both alcohol-related and nonalcohol advertisements. The findings of this study
      have implications for understanding both the influence of alcohol advertisements
      on behavior and the psychophysiological correlates of cue reactivity.

PMID- 9573432
TI  - Drug problem recognition among African American drug-using arrestees.
AB  - We examined demographic factors, drug-use severity indicators, social resources,
      and personal perceptions as correlates of Drug Problem Recognition among African
      American drug-using arrestees. In particular, we sought to move beyond the
      "ethnic gloss" of prior research by including ethnicity-related attitudes,
      perceptions, and experiences among the factors tested. Multivariate regression
      analysis suggested that Conventional Moral Beliefs and Neighborhood Drug/Alcohol
      Problems were key determinants of the perception that one's own drug use is a
      problem. We cite implications of these findings for help seeking and engagement
      in treatment among African American drug user.

PMID- 9573433
TI  - Female condom acceptability among sex workers in Costa Rica.
AB  - This study measured short-term female condom acceptability among 51 female sex
      workers in San Jose, Costa Rica. Each woman was trained in use of the female
      condom and was asked to use the device if clients refused to use male condoms
      during a 2-week study period (male condoms were also distributed). Two follow-up
      visits with short interviews were scheduled, including questions on general
      reaction to the female condom by the participants and their clients, ease and
      comfort of use, and preferences for male or female devices. At the first follow
      up visit, 51% of the women reported they "liked the female condom very much" and
      45% reported they "liked it somewhat." Similar results were reported after the
      second follow-up phase. Sixty-seven percent of the participants preferred the
      female condom over the male condom, and, according to the the women, over half of
      their clients liked the female condom "very much" or "somewhat." The most common
      problems during the first phase were difficulty to insert (61%) and discomfort
      (43%). However, during the second study phase a reduction in these problems (22%
      and 25%, respectively) and other use-related problems were noted. Although this
      new method is not yet available throughout Costa Rica, these results should
      encourage sexually transmitted diseases and HIV service organizations to make
      this method accessible to women.

PMID- 9573434
TI  - Barriers and pathways to testing among HIV-infected women.
AB  - Through in-depth interviews the testing experiences of HIV-infected women were
      examined. The barriers that impeded the women from recognizing their at-risk
      status and from seeking testing once their vulnerability was acknowledged are
      discussed. Also described are the pathways that led women into testing. The data
      reveal that lack of understanding about risk behaviors, ignorance of their
      partner's risk practices, lack of information about HIV-related symptoms, and
      perceived invulnerability to infection were the principal barriers to women
      recognizing their at-risk status. The women's accounts also indicate that
      psychological factors--fear and denial--are the principal barriers to seeking
      testing once one acknowledges vulnerability. Finally, the data show that few
      women made a thoughtful proactive decision to be tested but rather seemed to be
      led by circumstances to learn their status, sometimes unwittingly.

PMID- 9573435
TI  - The Healthy for Life project: sexual risk behavior outcomes.
AB  - Sexual risk behavior outcome data from the Healthy for Life (HFL) project is
      presented. Using a social influences model, the intervention was designed to
      positively affect the health behaviors of middle school students in five related
      areas: alcohol use, tobacco use, marijuana use, nutrition, and sexuality. The in
      school program was supplemented by parent, community and peer components. The
      research used self-report data on an initial sample of 2,483 middle school
      students followed from Grade 6 to Grade 10. Twenty-one schools were assigned to
      three conditions--age appropriate (program taught in Grades 6, 7, and 8),
      intensive (program taught in Grade 7) and control--using blocked randomization.
      Attrition was 20% (by Year 4) and 33% (by Year 5). By ninth grade the lifetime
      intercourse rate among both groups of HFL subjects was significantly higher than
      for controls (controlling for baseline substance use risk and involvement with
      the opposite sex), but reported past month intercourse rates and condom use did
      not differ. At the tenth grade follow-up, the age appropriate subjects reported
      higher adjusted rates of lifetime and past month intercourse than did the
      controls. Intensive subjects perceived significantly lower normative rates of
      intercourse than controls at ninth grade follow-up, but age appropriate subjects
      perceived significantly higher norms at tenth grade. Our expectation that this
      approach would be effective in reducing adolescent sexual risk behavior has not
      been supported. The influence of social and community norms and contextual
      factors has a far greater influence on the behavior of students (even 6 years
      later) than this school-based social influences program targeting only one grade
      cohort.

PMID- 9573436
TI  - Predictors of AIDS-preventive behavioral intentions among adult heterosexuals at
      risk for HIV-infection: extending current models and measures.
AB  - This study examined the predictors of the intention to use condoms with new
      sexual partners. A sample of heterosexual adult females and males (n = 711) was
      recruited through various channels. A substantial part of the sample had engaged
      in risky sexual behavior. Predictors were based on various theoretical models.
      Compared with men, women were in general more aware of the risks of AIDS and
      perceived fewer barriers to using condoms, but they also perceived less support
      for condom use among potential new partners. Among those with a risk factor for
      HIV infection (n = 514), various types of barriers, absolute and comparative self
      efficacy, and three types of social norms were independently related to the
      intention to use condoms. When including all relevant predictors, self-efficacy,
      anticipated regret, and descriptive norms in the reference group, were
      independent predictors of condom use intention among men as well as among women.
      The implications for prevention are discussed.

PMID- 9573437
TI  - Development of the AIDS Health Belief Scale (AHBS).
AB  - The AIDS Health Belief Scale (AHBS) was developed to measure the four components
      of the health belief model (HBM): perceived susceptibility to disease, perceived
      severity of a specific disease, perceived benefits of preventive behavior, and
      barriers to preventive behavior. Sixteen items were developed for the original
      AHBS. Results of the first phase of AHBS development showed that all 16 items
      correlating significantly (p < .001) with total AHBS scores, collected from 216
      undergraduate students. The second phase involved results from 401 completed
      AHBSs and demonstrated a high degree of internal consistency with alphas ranging
      from .82 to .93. In addition, factor analysis was conducted to determine the
      underlying structure of the scale. Results demonstrated that four factors
      (consistent with the four components of the HBM) explained 64% of the variance in
      response patterns. Implications for future HIV preventive research and education
      programs are discussed.

PMID- 9573438
TI  - Parental drug use and the socialization of AIDS knowledge and attitudes in
      children.
AB  - Children aged 6 to 18 who had a parent enrolled in drug treatment were matched on
      the child's age, sex, and ethnicity and on the parent's level of education with
      children from a community sample. They were compared with respect to parents'
      knowledge of HIV transmission, parents' efforts to teach their children (ages 6
      to 18) about HIV and AIDS, and children's knowledge and attitudes regarding AIDS.
      Children of drug-abusing parents had more direct and indirect experience with
      people affected by AIDS than other children, and they demonstrated more knowledge
      of HIV transmission, once other variables were controlled. Overall, however, few
      group differences in parents' knowledge and socialization efforts or in
      children's AIDS-related knowledge and attitudes were observed. Although children
      of drug abusers appear to be learning as much as other children about HIV and
      AIDS, they nonetheless deserve special attention as a group at risk for HIV
      infection.

PMID- 9573439
TI  - Primates as seed dispersers: ecological processes and directions for future
      research.

PMID- 9573440
TI  - Evolutionary and ecological implications of primate seed dispersal.
AB  - In this paper, we evaluate patterns of fruit eating and seed dispersal in monkeys
      and apes and draw an important distinction between 1) the ecological consequences
      of primates as seed dispersers and 2) the evolutionary implications of primates
      on the seed and fruit traits of the plant species they exploit. In many forest
      communities, primates act as both seed predators and seed dispersers and are
      likely to have an important ecological impact on patterns of forest regeneration
      and tree species diversity. Evidence from Kibale National Park, Uganda, and Manu
      National Park, Peru, as well as several other South American sites indicates that
      monkeys and apes display a wide range of fruit-processing behaviors, including
      spitting seeds, dropping seeds, masticating seeds, and swallowing seeds.
      Differences in consumer body size, diet, ranging patterns, and oral and digestive
      morphology result in different patterns in the distance and distribution of seeds
      from the parent plant. In the case of South American monkeys, for example,
      despite their relatively small body size, platyrrhines were found to exploit
      larger fruits and swallow larger seeds on average than did Old World monkeys and
      apes of the Kibale forest. We found little evidence to support the existence of a
      coevolutionary relationship between a single or set of primate dispersers and the
      particular plant species they disperse. This is due to variability in the manner
      in which monkeys and apes select fruits and treat seeds, the fact that many
      species of primates and nonprimates exploit and disperse the same fruit species,
      and the fact that extremely high levels of postdispersal seed, seedling, and
      sapling mortality serve to dilute the influence that any primate species may have
      on the recruitment of the next generation of adult trees. It is apparent that
      many primate lineages exhibit dental, digestive, and/or sensory adaptations that
      aid in the exploitation of particular food types and that many lineages of
      flowering plants have evolved characteristics of fruits and seeds that facilitate
      seed dispersal. However, in light of currently available data, we argue that
      these represent evolutionary rather than more strictly defined coevolutionary
      relationships.

PMID- 9573441
TI  - Seed dispersal by long-tailed macaques.
AB  - We review here the methods by which long-tailed macaques (Macaca fascicularis
      fascicularis) process seeds in Bukit Timah Nature Reserve, Singapore, and the
      factors that influence this. Feeding observations have revealed that these
      macaques either destroy seeds in their mouth with their teeth, spit them out
      whole from the mouth after removing much of the flesh, or else clean the flesh
      off them at the front of the mouth and then drop them. Absence of these observed
      behaviors is associated with the presence of intact seeds in the feces,
      indicating that macaques swallow some seeds whole. All these options were
      exhibited by one group of macaques and were not random alternatives; evidence
      links their frequency to the type of fruit (fleshy vs. dry) and the size of the
      seed(s). Adaptations of the mouth of long-tailed macaques, such as gape and the
      presence of well-innervated cheek pouches and relatively large incisor and
      postcanine teeth, are predicted to influence these thresholds strongly. In a
      faunally depleted reserve like Bukit Timah, this dispersal is effective, but we
      see no evidence in this of coevolution between macaques and fruits. Many seeds in
      the macaque diet are probably dispersed more effectively by other vertebrates,
      such as birds, bats, gibbons, and civets, when these are present. However, in
      sites where large vertebrates have been eliminated, macaques may become important
      for dispersing large, large-seeded fruits.

PMID- 9573442
TI  - Lowland gorillas and seed dispersal: the importance of nest sites.
AB  - Lowland gorillas eat the fruit and disperse the seeds of many tree species in the
      Lope Reserve, Gabon. This study aimed to show whether deposition of seeds at
      gorilla ground nest sites conferred any advantage for germination and seedling
      establishment as compared to the fate of seeds deposited in gorilla dung on
      trails or under parents. Four tree species were chosen for study, which had a
      range of fruit types and fruiting patterns but which were all important foods for
      gorillas. Data showed that gorillas removed significant quantities of seeds from
      all four species and deposited them in dung at nest sites or on trail. Nest sites
      were not always favorable for germination, but the most favorable sites permitted
      the best survival and growth of any of the seedlings, including those deposited
      in dung on trail or scatter-dispersed under or away from parent canopies. Initial
      performance in the first few weeks after deposition was not always indicative of
      long-term survival and growth, so data collection over 1-2 years was absolutely
      essential. The main factors affecting seedling fate at nest sites appeared to be
      vegetation cover and desiccation. It is suggested that the nesting habits of
      gorillas are an additional factor encouraging the successful establishment of
      seedlings over and above the obvious advantages of large body size, gut capacity,
      and extended day ranges.

PMID- 9573443
TI  - Seed handling by three prosimian primates in southeastern Madagascar:
      implications for seed dispersal.
AB  - In this paper, we studied three species of prosimian primate (Propithecus diadema
      edwardsi, Eulemur fulvus rufus, and Eulemur rubriventer) from June-July 1995 at
      the Ranomafana National Park to answer three questions: 1) how they handle and
      process seeds, 2) how the physical properties of seeds influence seed handling
      and seed fate, and 3) whether handling and processing patterns influence seed
      dispersal. Seeds from five plant species were collected from feces and examined
      for external damage (punctures and scrapes), weighed, measured, and checked daily
      for germination. P. d. edwardsi masticated seeds into two or more pieces while
      feeding. Seed fragments were either dropped under the parent tree or chewed and
      swallowed; seeds never emerged as recognizable units in feces. In contrast, both
      Eulemur species either dropped or swallowed seeds whole while feeding. E.
      rubriventer passed seeds that were longer, wider, and heavier than seeds passed
      by E.f. rufus. Although seeds emerged as separate units when passed by both
      Eulemur species, 65 Protorhus sp. seeds were scraped and/or punctured prior to
      being swallowed. Based on physical property tests, Protorhus seeds were more
      susceptible to mastication than undamaged seeds from Eugenia sp., Cissus sp., and
      Chrysophyllum madagascariensis. H. madagascariensis seeds also were undamaged but
      had physical properties comparable to Protorhus and may avoid being masticated
      due to their small size (2-3 mm). All damaged seeds were moldy or rotten within 6
      days, and only 15% of the undamaged seeds passed by E. rubriventer germinated.
      None of the seeds passed by E.f. rufus germinated. Eulemur species also rested in
      the same tree after feeding and defecated prior to a new feeding bout or before
      moving, so seeds were most likely to be dispersed under the parent tree.
      Consequently, we concluded that these primate species do not appear to serve as
      effective seed dispersers for these plant species at this time of year.

PMID- 9573444
TI  - Variation in seed handling by two species of forest monkeys in Rwanda.
AB  - We examined temporal variability in the handling and dispersal of seeds by two
      sympatric species of monkeys, the arboreal blue monkey (Cercopithecus mitis
      doggetti) and the more terrestrial mountain monkey (C.l'hoesti). Ten months of
      data on phenological patterns and foraging behavior, including details of seed
      handling based on scan sampling data, were combined with dung sample data to
      examine patterns of seed handling. The systematic scan sampling observations
      showed that blue monkeys and mountain monkeys alternated between acting
      predominately as seed droppers, seed predators, and seed defecators depending on
      fruit resource availability. All the mountain monkey dung samples examined
      contained intact seeds, and 94% of the blue monkey dung samples contained intact
      seeds. Both monkey species defecated a greater number of seeds per dung sample
      and larger-sized seeds than found elsewhere for Cercopithecus monkeys. We found a
      mean of 2.33 and 6.43 seeds > 2 mm in blue and mountain monkey dung samples,
      respectively. The mountain monkeys dispersed relatively higher numbers of seeds
      and frequented open, disturbed forest, suggesting that terrestrial forest monkeys
      have been overlooked as potentially important seed dispersal agents. The
      variability in the ways seeds were handled was dependent on the array of
      available food resources and may suggest that the monkeys exert weak selective
      pressures on fruit traits.

PMID- 9573445
TI  - Seed dispersal by neotropical seed predators.
AB  - From a plant's perspective, the difference between a seed predator and a seed
      disperser should be straightforward: attract animals that will disperse seeds and
      defend seeds from potential predators. Unlike pulp-eating frugivores, seed
      predators regularly encounter diverse plant protective mechanisms. The purpose of
      this paper is to examine feeding constraints, morphological adaptations, and the
      mechanical process of seed predation. While there is evidence that some seed
      predators cause severe losses to seed crops, there is also evidence that seed
      predators enhance seed dispersal and germination. We also examine four methods by
      which neotropical seed predators may contribute to dispersal. 1) Seed predators
      examined here ingested fruit when seeds were full-sized, but not yet mature
      (i.e., seeds of mature fruit may be avoided by seed predators and available for
      dispersal by other frugivores). 2) Sympatric seed predators may ingest seeds from
      different plants thus reducing overall predator load on any individual plant. 3)
      Seed predators that manipulate seeds (e.g., remove pericarp and seed coat) may
      enhance germination if the prepared seeds are dropped, discarded, or buried and
      not ingested. 4) Small seeds may miss mastication and swallowed intact with a
      food bolus. The last mechanism is the most likely to contribute to seed dispersal
      by the widest array of vertebrate seed predators, but primate seed predators may
      facilitate seed dispersal using all four mechanisms. Therefore, the traditional
      dichotomy of seed predator vs. seed disperser oversimplifies the interactions
      between seed predators and plants.

PMID- 9573446
TI  - Forests without primates: primate/plant codependency.
AB  - Detailed studies of primates and fruiting trees have illustrated that these
      groups of organisms are involved in a very complex set of interactions, with
      primates relying on fruiting trees as important food resources and fruiting trees
      relying on frugivores for seed dispersal. Human activities that influence either
      primate seed dispersal or fruit production have the potential of having
      unanticipated effects on the other interactants. Here we evaluate what is known
      and what we still need to learn to evaluate the long-term consequences of
      disrupting the interactions between primates and tropical forest trees. We do
      this by first assessing the potential importance of primates at dispersing the
      seeds of tropical forest trees. Second, we consider possible consequences of
      hunting primates on recruitment in tropical tree communities. Third, we address
      the converse by considering the impacts of decreasing resource availability for
      primates through either logging or through the extraction of nontimber forest
      products. Finally, we provide a case study from Kibale National Park, Uganda,
      that contrasts seedling recruitment in 20 forest fragments in which primate seed
      dispersers have been dramatically reduced with seedling recruitment in areas that
      have an intact frugivore community. In comparison to the intact forest, the
      fragments had lower seedling density and fewer species of seedlings. Furthermore,
      a greater proportion of the seedlings were from small-seeded species that might
      not require primates for their dispersal, since they probably can be dispersed by
      small birds. All of these considerations suggest that disrupting the complex
      interactions between primates and fruiting trees can potentially have negative
      and possibly cascading effects on ecosystem processes.

PMID- 9573447
TI  - A note on the making of culinary tradition--an example of modern Japan.
AB  - This article deals with the transition of Japanese food culture in the late
      nineteenth and the first half of the twentieth century. It explains the three
      main stages of this transition, namely the adoption of Western haute cuisine by
      the Japanese elite, the diffusion of Western ingredients, dishes and cookery
      techniques among the urban middle class, and the popularization of the new
      Japanese-Western hybrid cuisine by the military. This new cuisine began to
      acquire the status of culinary "tradition" from the 1950s onwards. Dietary
      changes in modern Japan were to a large extent a consequence of deliberate
      policies of the government. In the early stage, Westernization of the elite's
      diet was regarded as necessary in order to achieve a status of a "civilized"
      nation. Later, deliberate dietary reforms were undertaken with the aim of
      improving physical conditions of the population. These deliberate actions were
      directly influenced by the political circumstances in which Japan found itself in
      the period discussed.

PMID- 9573448
TI  - Plasma leptin and hunger ratings in healthy humans.
AB  - Leptin, the ob gene product, is considered as a signal involved in the regulation
      of energy stores through centrally mediated effects on ingestive behavior and
      metabolism. To investigate the relationships between appetite-related sensations
      and circulating leptin in humans, 12 healthy male volunteers were served two test
      lunches (1200 kcal, 38% carbohydrate, 50% fat, 12% protein) with comparable
      palatability but resulting in different postprandial hunger ratings, and plasma
      leptin concentrations were monitored during 8 h after meal ingestion. Whereas
      postprandial hunger ratings (assessed by visual analog scales) and plasma insulin
      patterns differed significantly between meals, no significant difference in
      postprandial plasma leptin concentrations was observed between the two meals. A
      moderate but significant increase in mean plasma leptin was found over time. We
      conclude that postprandial plasma leptin concentrations do not significantly
      differ between two meals inducing different effects on hunger subjective
      feelings. These data are in agreement with a role for leptin in the regulation of
      energy balance as a long-term adiposity-related signal rather than a short-term
      meal-related factor.

PMID- 9573449
TI  - Perception and role of fruit in the workday diets of Scottish lorry drivers.
AB  - Forty-six lorry drivers working for two haulage firms in central Scotland took
      part in a study to determine their perception and the role of fruit in their
      diets on working days. A focus group session provided initial insights, with
      repertory grid being used to provide further understanding. Eating while at work
      was characterized by a pattern of extensive and irregular snacking. The snack
      foods tended to be branded items obtained from garage kiosks, forecourts,
      motorway service areas and truck stops. Fruit as a snack, although perceived as
      healthy, did not feature highly because it was considered both inconvenient and
      expensive. The study identifies a major role to be played by the roadside
      catering and retailing industries in supplying healthy snacks to their customers.

PMID- 9573450
TI  - Teenage vegetarianism: prevalence, social and cognitive contexts.
AB  - The aim of this study was to measure the prevalence of teenage vegetarianism and
      associated food habits and beliefs. Two thousand senior secondary school students
      (mean age 16 years), from 52 schools in South Australia, participated in a two
      part survey. The findings show that teenage vegetarianism is primarily a female
      phenomenon, ranging in prevalence, according to definition, from 8 to 37% of
      women and 1 to 12% of men. Support for vegetarian practices was high especially
      from mothers (63%) and classmates (46%). Generally, "teenage vegetarians"
      consumed fewer red meats than non-vegetarians but ate more chicken. They cited
      health, animal welfare and environmental reasons in support of their habits. The
      importance of operational definitions of vegetarianism is emphasized and the
      findings are discussed in relation to likely motivational influences.

PMID- 9573451
TI  - Videotape assessment of changes in aberrant meal-time behaviors in anorexia
      nervosa after treatment.
AB  - This study compared meal-time behaviors in patients with anorexia nervosa to
      normal-weight controls and the effects of hospital treatment on these behaviors.
      Ten restricting-anorexics and six normal-weight controls were given a standard
      lunch and asked to eat the entire meal. Their behaviors were recorded via hidden
      camera. All participants were tested twice--anorexics before and after in-patient
      treatment, and controls at similar intervals. Videotapes of these sessions were
      analysed for occurrence and duration of eight categories of non-ingestive
      behaviors: food manipulation, food preparation, food moving, non-food
      manipulation, concealment, vigilance, passivity and physical activity. Food
      ingestion patterns, including number of bites of food and switches between
      different kinds of food, were also recorded. Results indicated that anorexics
      spent significantly more time than controls in behaviors that were directly food
      related, and exhibited more vigilance behavior. Pre-treatment anorexics spent
      significantly more time in these behaviors than did post-treatment anorexics. Few
      group differences or treatment effects were found in food-ingestion patterns,
      although there was an indication that both pre- and post-treatment anorexics
      avoided high-fat foods more than controls did. These results suggest that
      videotaping provides a useful technique for characterizing the behavior
      associated with eating disorders. Further studies should explore whether
      normalization of these behaviors is associated with a positive clinical outcome.

PMID- 9573452
TI  - Attitudes towards meat-eating in vegetarian and non-vegetarian teenage girls in
      England--an ethnographic approach.
AB  - This study compared vegetarian and non-vegetarian teenage English girls'
      attitudes towards meat. A convenience sample of 15 vegetarian (mean age 17.2
      years) and 15 non-vegetarian (mean age 17.3 years) girls was recruited from a
      teenage health clinic. Attitudes towards meat were assessed in a single, tape
      recorded, semi-structured interview. Eight themes of the cultural meaning of meat
      were identified; five were common to both groups: Animal (66% of vegetarians, 33%
      of non-vegetarians); Taste/Texture/Smell (66%, 60%); Flesh and Blood (86%, 26%);
      Colour (33%, 20%); Miscellaneous (60%, 46%). The theme Eating Well was unique to
      the non-vegetarian group (40%). The themes Life/Death and Health-related were
      unique to the vegetarian group (66 and 20%, respectively). The vegetarians
      generally abhorred killing animals for food, meat's sensory characteristics and
      ingesting blood. A meat-free diet was not particularly associated with health in
      either group. The non-vegetarians tended to characterize meat positively, both
      liking meat's sensory characteristics and associating meat with luxury and
      special occasions. We speculate on possible reasons for the current popularity of
      vegetarianism in teenage girls.

PMID- 9573453
TI  - The effect of soup on satiation.
AB  - We compared the influence of three solid/liquid preloads to a no-preload
      condition given at lunchtime on hunger ratings and energy intake of the lunch and
      subsequent dinner in 12 lean and 10 overweight young men. The preloads
      (vegetables and water, strained vegetable soup, chunky soup) were of the same
      composition and volume but differed in distribution of nutrients between the
      liquid and the solid phases, and in the size of solid particles. Hunger ratings
      were reduced by the preloads; there was a significantly greater suppression of
      hunger after the chunky soup than after the vegetables and water. In both groups,
      the soups reduced energy intake at lunch, although the chunky soup had the most
      effect. In the overweight subjects, a reduced lunch intake was also followed by a
      reduced dinner intake. The benefit to weight control of large particles in soup
      should be evaluated.

PMID- 9573454
TI  - Reasons for initiation and cessation of eating in obese men and women and the
      affective consequences of eating in everyday situations.
AB  - Reasons for the initiation and termination of eating were investigated in 78
      female and 36 male obese subjects following a weight control programme. Self
      monitoring diaries were completed during a 24-h period, in which subjects
      selected the main reason for starting and stopping an eating episode.
      Additionally, subjects recorded mood before and after eating using visual
      analogue scales. Hunger was chosen as a reason to start eating in only 20% of
      cases. Environmental cues such as mealtime were selected as the main reason for
      the initiation of the majority of eating episodes. In contrast, self-assessments
      such as "I felt I had eaten enough" was the main reason for terminating eating
      (39.4%). Gender differences in the reasons for initiating eating revealed a
      greater tendency for men to initiate eating for environmental reasons than women,
      whereas the opposite was found for the termination of eating, with women more
      likely to stop eating for environmental reasons than men. Changes in affect
      during eating revealed a significant decline in negative emotions such as tension
      and tiredness, and in the heavier subjects a trend for increased happiness was
      observed following eating. As hunger was less commonly reported as a reason to
      start eating than external reasons, treatment strategies for the obese might
      benefit by targeting individual reasons for meal initiation.

PMID- 9573455
TI  - Spatial cues are relevant for learned preference/aversion shifts due to amino
      acid deficiencies.
AB  - Rats are able to choose appropriately between two versions of a novel diet, when
      one is amino-acid devoid and the other corrected. Recognition of the deficiency
      has been reported to occur within hours and to initiate a strong conditioned
      aversion. For that purpose the rat can use either oro-sensory cues or another
      alternative as the conditioned stimulus (CS) with which to associate the
      unconditioned stimuli (US) of either the adequate diet or the devoid diet. The
      present investigation was designed to determine whether rats have the ability to
      use place as a cue in amino-acid preference/aversion. In order to avoid
      interfering with any other than spatial sensory discrimination between the devoid
      diet and its corrected version, rats were offered two food cups containing an
      identical threonine-devoid diet. This was supplemented with an intra-gastric
      delivery of either threonine or its vehicle, that varied according to the
      position of the feeder from which the rats had chosen to eat. After three choice
      sessions, rats chose the food container on the side corresponding to the
      threonine load. Our results showed that rats use place as a cue for an amino-acid
      replete nutritional state by learning a conditioned place preference/aversion and
      that they achieve this type of learning in spite of the long delay elapsing
      between CS and US.

PMID- 9573456
TI  - Determinants of energy balance in rats selectively bred for susceptibility or
      resistance to diet-induced obesity.

PMID- 9573457
TI  - Hypoxic-ischaemic encephalopathy is associated with regional changes in cerebral
      blood flow velocity and alterations in cardiovascular function.
AB  - Doppler-derived indices of cerebral blood flow velocity (CBFV) and
      echocardiographic parameters of left ventricular function were measured in 18
      patients with hypoxic-ischaemic encephalopathy HIE (group I) and in 28 normal
      controls (group II). Group-I infants had a subnormal distribution of CBFV values
      increasing over the first 85 h postnatally. CBFV values were constantly higher in
      the internal carotid than in the anterior cerebral artery. During the first 24 h
      postnatally, pulsatility and resistance indices of cerebral blood flow were
      significantly higher in group-I patients. From 30 to 85 h after birth, resistance
      indices were lower in group-I infants with severe HIE. Depressed left ventricular
      function and/or hypotension was documented in 50% of group-I patients.

PMID- 9573458
TI  - Use of teicoplanin in preterm neonates with staphylococcal late-onset neonatal
      sepsis.
AB  - OBJECTIVE: To study the clinical pharmacology of teicoplanin in babies admitted
      to a newborn intensive care unit, by monitoring serum levels, efficacy and
      potential side effects. METHODS: An open, nonrandomized descriptive study was
      performed in the neonatal intensive and high care unit of the University Hospital
      Maastricht, The Netherlands. Twenty-three preterm neonates, gestational age
      ranging from 26 to 32 weeks (median 28.4 weeks), postnatal age from 5 to 47 days,
      and birth weight from 570 to 1,740 g, presenting with (suspected) late onset
      septicemia, were studied. Of 21 culture-proven septicemias, 20 were caused by
      staphylococci. The teicoplanin loading dose was 15 mg/kg i.v., followed by a
      maintenance dose of 8 mg/kg every 24 h. Intravenous gentamicin was also
      administered pending blood culture. Serum teicoplanin concentrations were
      measured by fluorescence polarization immunoassay. Clinical and microbiological
      cure/failure rates were determined and possible side effects were monitored.
      RESULTS: The study of individual pharmacokinetics during multiple-dose
      intravenous infusions was rendered impossible by apparently inaccurate dosing.
      Peak (30 min after end of the infusion) and trough teicoplanin levels were stable
      throughout the study and averaged 27.8 (interquartile range 23.7-32.9) and 12.3
      (interquartile range 9.1-16.8) mg/l, respectively. The microbiological and
      clinical cure rates were 90% in gram-positive septicemia. There was no apparent
      toxicity. CONCLUSIONS: Inaccurate drug administration was a problem in this
      study, making a multidose pharmacokinetic study impossible. It is possible that
      inaccurate drug administration and not current dosage guidelines yielded trough
      levels below 10 mg/l in 57 (32%) of 176 instances. This pharmaceutical aspect
      clearly warrants further study. However, microbiological and clinical cure rates
      were high in gram-positive septicemias. No side effects attributable to
      teicoplanin therapy were encountered.

PMID- 9573459
TI  - Delivery of total parenteral nutrition (TPN) via umbilical catheterization:
      development of a piglet model to investigate therapies to improve
      gastrointestinal structure and enzyme activity during TPN.
AB  - Nutritional support of preterm infants by total parental nutrition (TPN) is
      common; however, TPN compromises intestinal structure and enzyme activity. Our
      goal was to develop a piglet model to assess the effect of limited enteral
      stimulation with formula and insulin-like growth factor-I (IGF-I) on intestinal
      morphology and enzyme activity. A nutritionally complete TPN solution was infused
      for 7 days and piglets were gavaged twice daily with 4 ml sterile water, formula,
      or formula containing 1,000 micrograms/l IGF-I. Litter mate piglets fed formula
      served as orally fed controls. On day 7, body weights and plasma hormone profiles
      of TPN and orally fed piglets were similar. However, intestinal weight, jejunal
      and ileal villus height and surface area, and mucosal lactase and sucrase
      activity of TPN piglets was reduced by approximately 50%. No effect of limited
      enteral stimulation or IGF-I was observed likely due to the small volume of
      formula administered enterally, which resulted in a low dose of IGF-I (4.3
      micrograms IGF-I/kg/day).

PMID- 9573460
TI  - Effect of age on furosemide-induced nephrocalcinosis in the rat.
AB  - Furosemide (F)-induced nephrocalcinosis (NC) has been traditionally described in
      low birth weight premature infants. To investigate the role of age on F-induced
      nephrocalcinosis we studied 24 Sprague-Dawley male rats grouped by age and F
      therapy vs. control as follows: A (4-week-old control), B (4-week-old + F), C (6
      week-old control), D (6-week-old + F), E (10-week-old control), F (10-week-old +
      F). The rats were placed in metabolic cages for measurement of urine output, food
      and water intake. At day 14 they were anesthetized, exsanguinated and their
      kidneys harvested. Renal calcium deposition was assessed using NC score (scale 0
      4) and quantitative calcium analysis in the contralateral kidney. Treated animals
      gained less weight and had higher urine output and fluid intake than the age
      matched controls demonstrating the diuretic effect of furosemide. Control groups
      A, C, and E scored 0 histologically compared with B 2.75 +/- 0.50, D 2.00 +/-
      0.58, and F 3.00 +/- 0.82 (p < 0.05 in all three paired groups). Kidney calcium
      content (micrograms/g dry weight) in B was 2,815.68 +/- 1,553.77 vs. A 202.58 +/-
      32.02 (p = 0.04); D 1,574.05 +/- 540.21 vs. C 212.22 +/- 30.91 (p = 0.02); F
      2,591.40 +/- 1,269.80 vs. E 210.38 +/- 26.79 (p = 0.02). There was no difference
      in the magnitude of NC among the three treated groups themselves. To determine
      the possible effect of age on timing of onset of NC additional 30 4-week-old and
      30 10-week-old rats were studied. All 60 rats received furosemide. Six rats from
      each group were sacrificed on days 1, 3, 5, 7 and 11. In both groups, significant
      calcifications were seen already on day 3 and maximum calcification noted between
      days 3 and 5. We conclude that in this model the development of NC occurs within
      a few days of furosemide administration and that this phenomenon is not age
      dependent but rather reflects a property of the loop diuretic itself.

PMID- 9573461
TI  - Brief, intermittent hypoxia restricts fetal growth in Sprague-Dawley rats.
AB  - This study was conducted to determine whether brief, intermittent exposure to
      hypoxia with little change in nutrient intake would affect fetal growth. Pregnant
      rats were exposed to 1 or 2 h of hypoxia (FiO2 = 0.09-0.095) from days 15 to 19
      of gestation. Exposure to 1 h of hypoxia decreased fetal body weight and length,
      liver weight and increased the brain/liver weight ratio (p < 0.05) as compared to
      controls. Two hours of hypoxia decreased fetal body weight and length, and heart,
      lung, kidney, gut, brain and liver weights (p < 0.01), but did not affect the
      brain/liver weight ratio. Two hours of hypoxia decreased maternal food intake and
      weight gain (p < 0.05), but fetal growth was not significantly altered in pair
      fed controls. These data demonstrate that brief, intermittent periods of
      intrauterine hypoxia have significant effects on fetal growth.

PMID- 9573462
TI  - Enhancement of surfactant effect by a mechanical volume recruitment maneuver
      depends on the lungs preexisting distension.
AB  - 'Rescue' surfactant treatment of premature infants with respiratory distress
      syndrome (RDS) results in two mechanisms: stabilization of alveoli already being
      ventilated and recruitment of alveoli collapsed before surfactant administration.
      Mechanical recruitment of alveoli from this collapsed compartment might enhance
      the immediate effects of surfactant treatment. To test this hypothesis 15
      mechanically ventilated young rabbits underwent repeated airway lavage with
      normal saline at a constant, positive end-expiratory pressure (PEEP) of 3 cm H2O
      until both the a/A ratio was < 0.12 and a peak inspiratory pressure (PIP) > 20
      mbar was needed to keep the tidal volume (VT) at 10 ml/kg. Surfactant (Survanta)
      was given over 4 min in conjunction with a mechanical volume recruitment maneuver
      (VRM) which consisted of an increased PIP by 33% of baseline values. The effects
      of surfactant were assessed using two indices of gas exchange (a/A ratio and
      PaCO2), four indices of lung function (functional residual capacity, FRC, dynamic
      lung compliance, Crs, VT and the alveolar portion of VT) and postmortem pressure
      volume curves and were compared with two groups of rabbits receiving surfactant
      alone or no surfactant at all. VRM yielded an increase in Crs by +22% whereas VT
      increased by +58% suggesting overdistension of terminal airways to some extent.
      There were no differences between the surfactant and the VRM + surfactant groups
      for all indices assessed after an observational period of 2 h following
      surfactant administration. In a previous model using a PEEP of 1 cm H2O [Krause
      et al., Am J Respir Crit Care Med 1997;156:862-866], significant differences have
      been disclosed for Crs, VT and FRC. In conclusion, the enhancement of surfactant
      effect by VRM largely depends on the preexisting distension of the lungs.

PMID- 9573463
TI  - Endogenous bradykinin regulates renal function in the newborn rabbit.
AB  - The developmental changes in the activity of the renal kallikrein-kinin system
      (KKS) are related to the hemodynamic changes occurring in the neonatal kidney. In
      order to clarify the functional importance of the renal KKS in the developing
      kidney, the effect of the bradykinin B2 receptor antagonist HOE-140 was
      investigated in newborn rabbits. Effective blockade of bradykinin effect by HOE
      140 was demonstrated in 10 rabbits. In 10 additional animals the subcutaneous
      injection of 300 micrograms/kg HOE-140 resulted in an increase in renal vascular
      resistance with a consequent decrease in renal blood flow. Glomerular filtration
      rate did not change significantly, while the filtration fraction rose, indicating
      preferential efferent arteriolar constriction. Urine flow rate increased as well
      as the fractional excretion of potassium. No change in sodium excretion was
      observed. The present data suggest a regulatory role for the renal KKS in the
      immature kidney under basal conditions. By inducing predominant efferent
      arteriolar vasodilation, the KKS appears to play a key role in regulating the
      neonatal glomerular microcirculation. This is in sharp contrast with the mature
      kidney, where the KKS predominantly acts on tubular function as a diuretic
      natriuretic factor.

PMID- 9573464
TI  - Possible protection by breast-feeding against severe esophageal and gastric
      lesions in the neonate. A case-control study.
AB  - The development of safe fiberoptic endoscopy in neonates led to the
      identification of the occurrence of severe esophageal and gastric lesions (EGL)
      in the first days of life. The cause of these early acute lesions, which are
      associated most of the time with severe clinical symptoms, remains unknown. 34
      neonates with EGL were compared with controls born in the same maternity unit
      immediately after those enrolled in the EGL series. Clinical and obstetric data
      were not different in the 2 groups. Breast-feeding was less frequent (p < 0.01)
      and given later (p = 0.0001) in babies with EGL. This retrospective analysis
      yielded no indication relative to the causative phenomenon leading to such
      mucosal alterations. In contrast, it provides the first evidence of a possible
      protective role of breast-feeding.

PMID- 9573466
TI  - Precision agriculture: spatial and temporal variability of environmental quality.
      Symposium proceedings. Wageningen, The Netherlands, 21-23 January 1997.

PMID- 9573465
TI  - Effects of endotoxemia and sepsis on bilirubin oxidation by rat brain
      mitochondrial membranes.
AB  - Sepsis is believed to increase the risk of bilirubin brain toxicity, but the
      mechanism is not known. Adult male Sprague-Dawley rats were injected
      intraperitoneally with either 20 mg/kg Escherichia coli lipopolysaccharide,
      approximately 5 x 10(9)/kg CFU Listeria monocytogenes or vehicle 48 h prior to
      sacrifice. Rats were killed with an intraperitoneal injection of pentobarbital.
      Mitochondrial membrane fractions were produced by homogenization of the brains
      and differential centrifugation in 0.32 M sucrose. The mitochondrial pellet was
      resuspended in distilled water and sonicated to rupture the mitochondria. The
      protein concentration of the suspension was standardized to 2.5 mg/ml. Bilirubin
      oxidation was assayed in a pH 8.2, 0.1 M barbital buffer containing 10 microM
      bilirubin, 5 mM EDTA, and 500 U/ml catalase. Optical density was measured at 440
      nm before and after a 60-min incubation at 37.5 degrees C. There were no
      differences between the control, endotoxemic, and septic groups as far as the
      ability of brain mitochondrial membranes to oxidize bilirubin (bilirubin
      oxidation rate: 289 +/- 11 vs. 295 +/- 9 vs. 296 +/- 12 pmol/min/mg protein, mean
      +/- SD). We conclude that endotoxemia or sepsis do not change the ability of
      brain mitochondrial membranes to oxidize bilirubin. If sepsis truly increases the
      risk of bilirubin encephalopathy in neonatal jaundice, this is likely to involve
      other mechanisms.

PMID- 9573467
TI  - Precision agriculture: introduction to the spatial and temporal variability of
      environmental quality.
AB  - Precision agriculture aims at adjusting and fine-tuning land and crop management
      to the needs of plants within heterogeneous fields. Production aspects have to be
      balanced against environmental threshold values and modern information technology
      has made it possible to devise operational field systems. A reactive approach is
      described, using yield maps and sensors. A proactive approach uses simulation
      modelling of plant growth and solute fluxes to predict optimal timing of
      management practices. Precision agriculture, combining both approaches, is seen
      as making a major contribution towards the development of sustainable
      agricultural production systems.

PMID- 9573468
TI  - Spatial variability of soil moisture regimes at different scales: implications in
      the context of precision agriculture.
AB  - Precision agriculture is based on the concept of soil-specific management, which
      aims to adapt management within a field according to specific site conditions in
      order to maximize production and minimize environmental damage. This paper
      examines how the nature and sources of variation in soil moisture regimes affect
      our ability to simulate soil water behaviour within a field with adequate
      precision in order to advise optimal soil-specific management. Field examples of
      variation in soil moisture regimes are described to illustrate the difficulties
      involved. A discussion identifies three main points. First, it is recognized that
      the current modelling approaches to soil moisture regimes do not sufficiently
      account for local heterogeneities in soil and crop characteristics such as soil
      morphology and rooting patterns. Second, the estimation of within-field variation
      of soil hydraulic properties is difficult because of large short-range variation
      of the properties and general lack of observed data; one way to overcome this
      problem is to seek new measurement techniques or to find easy-to-measure
      auxiliary variables spatially correlated to the variables of interest. Last, as
      pollution impacts often become noticeable to society at scales larger than the
      scale of agricultural management, hydrological modelling can serve for linking
      both scales and advising agricultural practices that minimize undesirable
      pollution effects.

PMID- 9573469
TI  - Modelling non-stationary spatial covariance structure from space-time monitoring
      data.
AB  - Accurate interpolation of soil and climate variables at fine spatial scales is
      necessary for precise field management. Interpolation is needed to produce the
      input variables necessary for crop modelling. It is also important when deciding
      on regulations to limit environmental impacts from processes such as nitrate
      leaching. Non-stationarity may arise due to many factors, including differences
      in soil type, or heterogeneity in chemical concentrations. Many geostatistical
      methods make stationarity assumptions. Substantial improvements in interpolation
      or in the estimation of standard errors may be obtained by using non-stationary
      models of spatial covariances. This paper presents recent methodological
      developments for an approach to modelling non-stationary spatial covariance
      structure through deformations of the geographic coordinate system. This approach
      was first introduced by Sampson & Guttorp, although the estimation approach is
      updated in more recent papers. They compute a deformation of the geographic plane
      so that the spatial covariance structure can be considered stationary in terms of
      a new spatial coordinate system. This provides a non-stationary model for the
      spatial covariances between sampled locations and prediction locations. In this
      paper, we present a cross-validation procedure to avoid over-fitting of the
      sample dispersions. Results concerning the variability of the spatial covariance
      estimates are also presented. An example of the modelling of the spatial
      correlation field of rainfall at small regional scale is presented. Other
      directions in methodological development, including modelling temporally varying
      spatial correlation, and approaches to model temporal and spatial correlation are
      mentioned. Future directions for methodological development are indicated,
      including the modelling of multivariate processes and the use of external
      spatially dense covariables. Such covariates are frequently available in
      precision agriculture.

PMID- 9573470
TI  - Ecological constraints on the ability of precision agriculture to improve the
      environmental performance of agricultural production systems.
AB  - In this paper, I address three topics relevant to the ability of precision
      agriculture to improve the environmental performance of agricultural production
      systems. First, I describe the fundamental ecological factors that influence the
      environmental performance of these systems and address how precision agriculture
      practices can or cannot interact with these factors. Second, I review the
      magnitude of the ecological processes that we hope to manage with precision
      agriculture relative to agricultural inputs to determine whether managing these
      processes can significantly affect system environmental performance. Finally, I
      address scale incongruencies between ecological processes and precision
      agriculture techniques that could limit the ability of these techniques to manage
      variability in these processes. The analysis suggests that there are significant
      ecological constraints on the ability of precision agriculture techniques to
      improve the environmental performance of agricultural production systems. The
      primary constraint is that these techniques do not address many of the key
      factors that cause poor environmental performance in these systems. Further, the
      magnitude of the ecological processes that we hope to manage with precision
      agriculture are quite small relative to agricultural inputs and, finally, these
      processes vary on scales that are incongruent with precision management
      techniques.

PMID- 9573471
TI  - Predicting wheat yields: the search for valid and precise models.
AB  - Interest in predicting wheat yield in terms of physiological, cultural and
      meteorological variables is more than a century old. Early attempts involved
      statistical analyses of relationships between yield and observational data on
      precipitation, temperature, radiation, etc., and scientific study of
      physiological and cultural influences such as dates of sowing or anthesis,
      farming procedures and soil treatments. More recently these have been augmented
      by large-scale mechanistic models of phenological development, such as AFRCWHEAT,
      CERES and SIRIUS, incorporating some simulation facilities. All approaches
      implicitly involve fitting models of some sort: statistical, mechanistic or
      (preferably) a hybrid of these forms. Levels of success on this important matter
      are highly variable. After reviewing the field, we consider the results of recent
      efforts to contrast and evaluate the (large-scale) mechanistic approaches, using
      spatial/temporal methods for interpolating the required climatological input
      variables. The work employs a substantial database of wheat yields assembled for
      this purpose. After assessing the validity of the large-scale mechanistic models
      (with some intriguing conclusions), we then consider some results from a current
      approach to parsimonious hybrid modelling, based on statistical study of
      accessible climatological data interpreted in terms of physiological knowledge of
      key influences on plant development.

PMID- 9573472
TI  - Geostatistics, remote sensing and precision farming.
AB  - Precision farming is possible today because of advances in farming technology,
      procedures for mapping and interpolating spatial patterns, and geographic
      information systems for overlaying and interpreting several soil, landscape and
      crop attributes. The key component of precision farming is the map showing
      spatial patterns in field characteristics. Obtaining information for this map is
      often achieved by soil sampling. This approach, however, can be cost-prohibitive
      for grain crops. Soil sampling strategies can be simplified by use of auxiliary
      data provided by satellite or aerial photo imagery. This paper describes
      geostatistical methods for estimating spatial patterns in soil organic matter,
      soil test phosphorus and wheat grain yield from a combination of Thematic Mapper
      imaging and soil sampling.

PMID- 9573473
TI  - Space-time statistics for decision support to smart farming.
AB  - This paper summarizes statistical procedures which are useful for precision
      farming at different scales. Three topics are addressed: spatial comparison of
      scenarios for land use, analysis of data in the space-time domain, and sampling
      in space and time. The first study compares six scenarios for nitrate leaching to
      ground water. Disjunctive cokriging reduces the computing time by 80% without
      loss of accuracy. The second study analyses wind erosion during four storms in a
      field in Niger measured with 21 devices. We investigated the use of temporal
      replicates to overcome the lack of spatial data. The third study analyses the
      effects of sampling in space and time for soil nutrient data in a Southwest
      African field. We concluded that statistical procedures are indispensable for
      decision support to smart farming.

PMID- 9573474
TI  - Variability and uncertainty in spatial, temporal and spatiotemporal crop-yield
      and related data.
AB  - Application of the theories of precision agriculture to the practicalities of
      broad-acre farming relies on successful handling of the ramifications of
      uncertainty in information, i.e. information pertaining to the spatial and
      temporal variation of those factors which determine yield components and/or
      environmental losses. This paper discusses the uncertainty of yield and related
      variables as measured by their spatial and temporal variance. The magnitude of
      these two components gives a suggestion as to the appropriate scale of
      management. Simultaneous reporting on spatial and temporal variation is rare and
      the theory of these types of process is still in its infancy. Some brief theory
      is presented, followed by several examples from the Rothamsted classic
      experiments, yield-monitoring experiments in Australia, a long-term barley trial
      in Denmark, and a soil moisture monitoring network. It is clear that annual
      temporal variation is much larger than the spatial variation within single
      fields. This leads to the conclusion that if precision agriculture is to have a
      sound scientific basis and ultimately a practical outcome then the null
      hypothesis that still remains to be seriously researched is: 'given the large
      temporal variation in yields relative to the scale of a single field, then the
      optimal risk aversion strategy is uniform management.'

PMID- 9573475
TI  - Spatial sampling.
AB  - Sampling in a spatial setting is typically done for the purpose of estimating or
      predicting a population quantity such as the total of a variable in a study
      region, to predict a new value at an unobserved site, or to find regions of high
      values for further study. Spatial covariance and conditional variance patterns
      have led to the use of designs such as systematic and stratified arrangements to
      increase precision and cluster or multistage sampling to increase cost
      effectiveness. In addition, adaptive procedures can be used to take advantage of
      patterns not discovered prior to the survey. An adaptive sampling design is one
      in which the procedure for selecting sites or units to include in the sample can
      depend on values of the variable of interest observed during the survey. For
      example, in a survey of an unevenly distributed insect species, neighbouring
      sites may be added to the sample whenever high abundance of the insects is
      encountered. Examples of adaptive designs include adaptive cluster sampling and
      adaptive allocation. Issues of design optimality or effectiveness and choice of
      inference methods with different types of designs will be discussed.

PMID- 9573476
TI  - GIS support for precision agriculture: problems and possibilities.
AB  - Precision farming aims to optimize the use of soil resources and external inputs
      on a site-specific basis. Base ingredients for research in the field of precision
      farming are spatial data, including a characterization of the spatial
      variability, and simulation models for the characterization of the processes that
      take place. Geographical information systems (GIS) are systems for the storage,
      analysis and presentation of spatial data. A combination of GIS and simulation
      models is highly relevant for precision farming. Currently only static one- or
      two-dimensional simulation models can be fully supported by commercial GIS
      systems. Within precision agriculture an engineering component can be also
      distinguished, in which the research findings are translated into operational
      systems for use at farm level. GIS can support this engineering activity by
      providing a good platform for storage of base data, simple modelling,
      presentation of results, development of a user interface and, in combination with
      a global positioning system, controlling the navigation of farm vehicles. On the
      basis of GIS a decision support system could be developed for operational
      application of precision agriculture at farm level.

PMID- 9573477
TI  - Modelling for precision weed management.
AB  - Recently, the need for the development of weed management systems with a reduced
      dependency on herbicides has increased because of concern about environmental
      side-effects and cost. The development of such systems requires new strategies
      based on improvements with respect to (1) prevention, (2) decision making and (3)
      weed control technology. For the development of improvements in all three
      aspects, quantitative understanding of weed population dynamics and crop-weed
      interactions is needed. Models that integrate the available quantitative
      knowledge can be used to design preventive measures, to develop long-term and
      short-term strategies for weed management, to assist in decision making to
      determine if, when, where and how weeds should be controlled and to identify new
      opportunities for weed control. Ecophysiological simulation models for crop-weed
      competition simulate growth and production of species in mixtures, based on
      ecophysiological processes in plants and their response to the environment. Such
      models help improve insight into the crop-weed system and can be used for
      purposes such as the development of simple predictive yield-loss models,
      threshold levels or the design of competitive crop plant types. For strategic
      weed management decisions, preventive measures and the identification of new
      opportunities for weed control, quantitative insight into the dynamics and
      spatial patterns of weed populations is also required. The complexity of the
      process and the long-term character of weed population dynamics make the use of
      models necessary. Different modelling approaches have been developed and are
      described briefly. Opportunities to use the available knowledge and models to
      improve weed management are discussed. Weeds occur in patches and their
      sensitivity to herbicides changes strongly with developmental stage, making
      precision techniques for herbicide application in time and space an option for
      reducing herbicide use. Limitations related to insight in biological processes as
      well as the state of technological development are discussed.

PMID- 9573478
TI  - Optimal mapping of site-specific multivariate soil properties.
AB  - This paper demonstrates how geostatistics and fuzzy k-means classification can be
      used together to improve our practical understanding of crop yield-site response.
      Two aspects of soil are important for precision farming: (a) sensible classes for
      a given crop, and (b) their spatial variation. Local site classifications are
      more sensitive than general taxonomies and can be provided by the method of fuzzy
      k-means to transform a multivariate data set with i attributes measured at n
      sites into k overlapping classes; each site has a membership value mk for each
      class in the range 0-1. Soil variation is of interest when conditions vary over
      patches manageable by agricultural machinery. The spatial variation of each of
      the k classes can be analysed by computing the variograms of mk over the n sites.
      Memberships for each of the k classes can be mapped by ordinary kriging. Areas of
      class dominance and the transition zones between them can be identified by an
      inter-class confusion index; reducing the zones to boundaries gives crisp maps of
      dominant soil groups that can be used to guide precision farming equipment.
      Automation of the procedure is straightforward given sufficient data. Time
      variations in soil properties can be automatically incorporated in the
      computation of membership values. The procedures are illustrated with multi-year
      crop yield data collected from a 5 ha demonstration field at the Royal
      Agricultural College in Cirencester, UK.

PMID- 9573480
TI  - Precision agriculture: spatial and temporal variability of environmental quality.
      General reflections.

PMID- 9573479
TI  - Uncertainty in hydrogeological modelling.
AB  - Hydrogeological models are built to predict groundwater flow and the fate of
      contaminants in the subsurface. After the crucial step of building a conceptual
      model that includes the processes that should be accounted for, parameter values
      must be assigned to the components of the model. Measured values of these
      parameters are available only at a few locations, as is the case for
      transmissivity, hydraulic conductivity or porosity. Therefore, before making
      predictions about the movement of contaminants in the aquifer, it is necessary to
      predict the parameter values at unsampled locations. Given the spatial
      heterogeneity of the parameters involved, this prediction is always uncertain.
      Model parameter uncertainty propagates to flow-response variables and further to
      transport predictions. Parameter uncertainty can be modelled using stochastic
      methods. Stochastic simulation is used for the generation of alternative spatial
      realizations of the parameter values, which are then used as input to groundwater
      flow and mass transport models to obtain frequency distributions of the response
      variables, e.g. flow velocities, arrival times or concentration levels. These
      frequency distributions help in making risk-qualified decisions. In order to make
      these frequency distributions as precise and accurate as possible, it is
      necessary to incorporate all relevant information in the parameter uncertainty
      model, i.e. it is necessary to condition the parameter realizations to all direct
      and indirect information. With this aim, new techniques have recently been
      developed in hydrogeological modelling. One such technique, for the generation of
      conductivity realizations conditioned to conductivity, piezometric head and
      geophysical data, is the self-calibrated method.

PMID- 9573481
TI  - Cell cycle checkpoints, chromosome stability and the progression of cancer.
AB  - During the evolution of normal cells into cancer cells, the occurrence of
      multiple mutations results in genetic instability. Mutations in DNA repair genes
      such as those of mismatch and excision repair predispose the carriers of these
      mutations to cancer by increasing the level of genomic instability. A variety of
      chromosome aberrations, such as abnormal ploidy, whole chromosome loss or
      chromosome amplification are commonly observed in cancer cells. From one cell
      division to the next, mammalian cells pass through an organized series of
      controlled events referred to as the cell cycle. In order to pursue an ordered
      series of molecular events, the initiation of an event during cell cycle
      progression is dependent on the successful completion of an earlier event. The
      cell cycle is divided into two major phases, namely, M(mitotic) phase and
      interphase. Interphase can be further divided into three distinct phases termed
      G1 (gap 1), S(DNA synthesis) and G2(gap2) phases (Fig. 1). Along with the
      machinery that promotes cell cycle progression, cells are also equipped with cell
      cycle checkpoints that ensure correct ordering of events in the cell cycle. The
      idea of "the cell cycle checkpoint" was first introduced by Hartwell and Weinert
      (1989) as "the arrest of a cell at a particular phase of the cycle due to a lack
      of appropriate signals for cell cycle progression". Until the checkpoint
      machinery receives the appropriate signal, the cell will not be allowed to make
      transition from one phase of the cell cycle to the next. Thus, the major role of
      checkpoint control is to minimize somatic genetic alterations and/or events
      affecting cellular survival. When one or more components of a cell cycle
      checkpoint are mutated, the chances of genetic instability during one round of
      the cell cycle increase accordingly with consequent acceleration of cellular
      evolution from the normal to the cancerous state. Therefore, mutations in
      checkpoint controls may predispose cells to cancer by causing genomic
      instability. In this review, I will focus on the potential roles of cell cycle
      checkpoints in the progression of malignancy.

PMID- 9573482
TI  - Some problems on fertilization and embryonic development in vitro in mammals.
AB  - Recently, progress of studies and technique developments on human and mammalian
      fertilization and early embryonic development in vitro are markedly. At the
      present time, however, some problems are remaining. In mammalian embryo culture,
      the major obstacles to progress in analysing epigenic regulation of development
      in other than the mouse and rabbit are the infamous blocks to development in
      vitro. At the present time, further studies are needed to dissolve the precise
      mechanism of these blocks. Factors which affect on embryo development are a great
      number and analysis of them is considered to be important for clinical
      application of the embryo culture system. Intracytoplasmic sperm injection(ICSI),
      at the present time, is employed widely for basic research and the treatment of
      male infertility. Using ICSI, recent studies are showing that mouse round
      spermatids can fertilize mature oocyte and the fertilized oocytes(embryos)
      develop into normal offspring after embryo transfer to foster mothers. Also, a
      recent report indicates development of normal mice from oocytes injected with
      secondary spermacyte nuclei. However, since some unsolved problems on
      spermatogenic cells such as round spermatids and secondary spermacytes remain,
      further studies are needed.

PMID- 9573483
TI  - Effects of feeder cells (human cancer cell lines) on the development of mouse
      embryos by co-culture.
AB  - In order to establish the best co-culture system on embryogenesis such as egg
      fertilization, egg cleavage, blastocyst formation, hatching and implantation
      etc., several kinds of cell lines as a feeder cell and mouse fertilized eggs
      (zygotes) were co-cultured in the organ culture dish, and embryotrophic effects
      of feeder cells were investigated. Best feeder cell on the embryogenesis was SKG
      II cell line derived from squamous cell carcinoma of human uterine cervix which
      was chosen from 10 of the human tumor cell lines. Furthermore, in order to
      isolate and determinate embryotrophic factors produced by feeder cells, we
      established a SKG-II SF subline which was grown in serum free medium derived from
      SKG-II cell line. The SKG-II SF cell line secreted an epidermal growth factor
      (EGF) into the medium. Also, cleavaged egg produced and secreted interleukin (IL)
      1 alpha into the medium.

PMID- 9573484
TI  - Factors affecting the development of oocytes and embryos in IVF-ET.
AB  - In our study in hMG/hCG protocol, there is correlation between basal FSH level
      and number of oocyte retrieved (Rs = -0.4334, p = 0.039). FSH was not useful in
      predicting poor responders in an in vitro fertilization program where pituitary
      desensitization is routinely used. There is correlation between day 2, day 3
      serum immunoactive inhibin level and number of follicle developed with hMG alone,
      or with hMG in conjunction with pituitary desensitization using a buserelin
      intranasal spray. The patients were divided by relationship between E2 peak and
      inhibin peak. The most of oocytes retrieved, oocytes fertilized and embryos
      cleaved were obtained when hCG was injected on the E2 peak day following the
      inhibin peak day. Inhibin concentration in aspirated follicular fluids was low
      and estradiol concentration was high in pregnant group. There is correlation
      between acceleration index of inhibin and number of oocyte retrieved in both
      protocols. Inhibin levels were significantly lower (P < 0.05) in women older than
      36 years of age, although estradiol responses were not so influenced by age.
      These data suggest that: (1) In the early follicular phase, inhibin may be a
      valid index to predict ensuing follicular growth and follicular development. (2)
      The serum inhibin responses to maximal ovarian stimulation may be a sensitive and
      early index of declining ovarian function with advancing age. (3) Inhibin is an
      important factor for the diagnosis of pregnancy outcome.

PMID- 9573485
TI  - Fertilization using male germ line-cells.
AB  - In recent years, favorable results have been achieved in patients suffering from
      azoospermia by microinsemination of spermatozoa taken from their testes.
      Microinsemination is being introduced in the treatment of patients who have no
      spermatozoa in their testes via their spermatid and spermatocyte. There are still
      doubts relating to immature male germ line-cells, such as whether they have,
      oocyte activating factors, the level of stability of DNA of cell nuclei, and the
      differences in chromosome numbers. The relatively few cases of gestation using
      the human spermatid treatment may be due to embryological problems resulting from
      the instability of nuclear DNA and the insufficiency of oocyte activating
      factors, which are the result of imperfect microinjection techniques.
      Improvements in techniques for the clinical application of spermatid and
      secondary spermatocyte, as well as the collection of basic data to confirm
      embryological safety are therefore necessary.

PMID- 9573486
TI  - A study on the correlation between maturation and quality of human oocytes.
AB  - The success ratio of live birth after human in vitro fertilization and embryo
      transfer program is still around 12% Per oocyte retrieval cycle. A large number
      of mature oocytes became degenerate and unable to develop after insemination or
      implantation. In order to determine this discrepancy, assessment of maturation
      process as well as cytoplasmic maturity of the oocyte was performed. Initiation
      and completion of maturation were dependent on steroid metabolism and cyclic AMP
      in the oocyte cytoplasm. Extracellular calcium is another determinant factor of
      oocyte maturation. Phosphorylation of 23.5kD and 29.5kD protein was observed in
      the cytoplasm during maturation. In addition to cAMP, nuclear maturation is
      regulated by protein tyrosine phosphorylation in the cytoplasm. An inhibitor of
      Na+/H+ antiport appears to be effective in the procedure of cryopreservation but
      has no relationship with oocyte maturation. Quality of the oocyte consists of
      nuclear and cytoplasmic maturation.

PMID- 9573487
TI  - Quality control of human IVF/ICSI program using endotoxin measurement and sperm
      survival test.
AB  - Quality control is essential for maintenance and improvement of a successful
      human in vitro fertilization and embryo transfer (IVF/ET)/intracytoplasmic sperm
      injection(ICSI) program. Quality control of medium, serum and equipments were
      performed using endotoxin measurement and human sperm survival test. It was
      proved by high pregnancy rate that the method of quality control at present study
      was essential for the development of the program.

PMID- 9573488
TI  - [Establishment and characterization of primitive neuroectodermal tumor cell line
      (UTO-EW1)].
AB  - New human primitive neuroectodermal tumor cell line, UTO-EW1 was established from
      the humeral bone tumor of a 25-year-old male patient. UTO-EW1 cells were found to
      be small round shaped and grew floating in the medium, or found to form
      monolayers in a polygonal shaped cells. The modal clomosomal number of the cells
      fell in a hypo-triploid range with several clonal clomosomal aberrations,
      including del(22) (q12). Neuron-specific enolase was positive by stained
      immunohistochemically. This cell line may be useful for basic studies and
      treatment of PNET.

PMID- 9573490
TI  - Comparative in vitro activities of four new fluoroquinolones against
      Streptococcus pneumoniae determined by Etest.
AB  - Clinafloxacin, levofloxacin, sparfloxacin and trovafloxacin were tested by Etest
      against 188 Streptococcus pneumoniae isolates. Clinafloxacin and trovafloxacin
      were 2-4-fold more potent than sparfloxacin and 8-fold more than levofloxacin.
      Two isolates, both serotype 6, with high-level quinolone resistance (> or = 8
      micrograms/ml) were detected. The Etest is a practical means for determining S.
      pneumoniae susceptibilities to new fluoroquinolones.

PMID- 9573489
TI  - Inhibitory effect of lead on tube formation by cultured human vascular
      endothelial cells.
AB  - The effect of lead acetate (Pb) on the formation of capillary-like structures
      (tube formation) by cultured human umbilical vascular endothelial cells (HUVECs)
      was examined. HUVECs were seeded on a gelled basement membrane matrix (Matrigel).
      Treatment of HUVECs with 0.3-30.0 microM Pb for 24 hours inhibited the tube
      formation dose-dependently. The length of tube formation decreased time
      dependently with 3.0-10.0 microM Pb. To elucidate the main target factor of Pb
      for this inhibition, the effects of Pb on the activity of protein kinase C (PKC)
      and Matrigel were examined. The addition of beta-phorbol 12-myristate 13-acetate
      (PMA, 50 nM), an activator of PKC, and isoquinolinesulfonamide derivative (H-7,
      30 microM), an inhibitor of PKC, showed an increase and decrease in the tube
      formation, respectively. However, the results of simultaneous addition of Pb and
      either PMA or H-7 to HUVECs indicated that PMA and H-7 acted not synergistically
      but additively. When PKC activities in HUVECs were measured by a colorimetric
      assay after treatments with 3.0-10.0 microM Pb for 24 hours, there was no
      significant change in PKC activity in the cells. The Pb-inhibition of tube
      formation was suggested to be independent of PKC activity. Pretreatment of
      Matrigel with 3.0-10.0 microM Pb for different periods decreased the tube
      formation dose- and time-dependently. These findings suggest that Pb can inhibit
      the tube formation by HUVECs dose- and time-dependently and that the inhibitory
      effect of Pb could be dependent on the degeneration of Matrigel, not on PKC
      activity.

PMID- 9573491
TI  - Retrospective study of teicoplanin as home continuation of hospital-initiated
      therapy.
AB  - Data were collected retrospectively on 69 cases of infection in 57 patients who
      had received teicoplanin on a non-inpatient basis for at least part of a course
      of therapy. A total of 52 records related to patients who were undergoing
      treatment for a hematological malignancy, most of whom had central venous
      catheter infection or catheter-related septicemia. Eleven cases were related to
      the treatment of bone and/or joint infection, two were concerned with the
      treatment of endocarditis and two were linked to soft tissue infections. In most
      cases in which bacteriological identification was made, coagulase-negative
      staphylococci were the causative organisms. Other pathogens included
      Staphylococcus aureus, streptococci, enterococci and diphtheroids. In most cases,
      the dose of teicoplanin used corresponded to the recommended dose for serious
      infections. All patients received teicoplanin intravenously and some patients
      administered the drug themselves. Clinical success (cure plus improvement) was
      achieved in 94% of evaluable cases and bacteriological success in 83%. Two
      adverse events were reported, but neither related to problems of antibiotic
      administration in a non-inpatient setting.

PMID- 9573492
TI  - Influence of adjunctive ticlopidine on the treatment of experimental
      Staphylococcus aureus endocarditis.
AB  - Antiplatelet therapy has been shown to reduce the size of aortic vegetations in a
      rabbit model of Staphylococcus aureus endocarditis. In addition, adjunctive
      aspirin improved the sterilization rate as compared with antibiotic treatment
      alone. To study the influence of ticlopidine, another potent inhibitor of
      platelet aggregation, infected animals received either vancomycin (Vm) alone or
      in combination with ticlopidine. When ticlopidine was given prior to and during
      antimicrobial therapy, a reduction in vegetation weight was observed. Ticlopidine
      administered with antimicrobial therapy, not only caused a reduction in
      vegetation weight, but also improved the rate of sterilization. This study
      provides additional data regarding the potential clinical role of antiplatelet
      agents in the treatment of endocarditis.

PMID- 9573493
TI  - Clinical use of antibiotics in dental practice.
AB  - Inappropriate use of antibiotics by clinicians leads to development of antibiotic
      resistance. For the most part, antibiotics are prescribed in dental practice for
      prophylactic and therapeutic reasons. Prophylactic antibiotics are prescribed to
      prevent diseases caused by members of the oral flora introduced to distant sites
      in a host at risk or introduced to a local compromised site in a host at risk. In
      most cases, prophylaxis is used for prevention of endocarditis. Therapeutic
      antibiotics are prescribed, in most cases, to treat diseases of hard and soft
      tissues in the oral cavity after local debridement has failed. Antibiotics used
      for prophylaxis must: (1) be active against the major pathogens; and (2) achieve
      a tissue loading dose before the bacteria are introduced. Antibiotics used for
      therapy are required in cases where the infection is already present and thus the
      agent must reach the site of infection at a high enough level for a long enough
      time to produce the desired effect. For an exogenous agent the goal is to
      eliminate the agent from the site of infection. In the case of an endogenous
      agent the antibiotic must suppress the organism at the site of infection. Recent
      evidence underscores the important role of antibiotics in the treatment and
      prevention of diseases initiated in the oral cavity that have the potential to
      spread to distant organs in the body.

PMID- 9573494
TI  - Subgingival controlled release of antimicrobial agents in the treatment of
      periodontal disease.
AB  - Local drug delivery of antimicrobics by sustained release delivery systems can be
      used to treat periodontal disease. Advantages of these systems may include
      biodegradation of the system, maintaining high levels of antibiotic in the
      gingival crevicular fluid (GCF) for a sustained period of time and ease of use
      with high patient acceptance. This review will identify human in vivo clinical
      and microbiological studies. Sustained release formulations, application methods,
      clinical results and microbiological effects are discussed.

PMID- 9573495
TI  - Antibiotic resistance mechanisms in bacteria of oral and upper respiratory
      origin.
AB  - Over the past 20 years, antibiotic resistance has increased in virtually every
      species of bacteria examined. In this paper, the main mechanisms of antibiotic
      resistance currently known for antibiotics used for treatment of disease caused
      by oral and upper respiratory bacteria will be reviewed, with an emphasis on the
      most commonly used antibiotics. The possible role that mercury, which is released
      from silver amalgams, plays in the oral/respiratory bacterial ecology is also
      discussed, as it relates to possible selection of antibiotic resistant bacteria.

PMID- 9573497
TI  - Intent-to-treat: a curse of clinical trials.

PMID- 9573496
TI  - Beta-sheet antibiotic peptides as potential dental therapeutics.
AB  - Small, cysteine-rich, beta-sheet peptide antibiotics are found throughout the
      Animalia. Though broad spectrum in potential, they may exert selective
      antimicrobial effects under certain conditions. We have explored the
      antimicrobial properties of two families of beta-sheet peptide antibiotics,
      defensins and protegrins, against periodontopathic bacteria. The rabbit defensin
      NP-1 was active against facultative Gram-negative bacteria associated with early
      onset periodontitis, including Actinobacillus actinomycetemcomitans and the
      Capnocytophaga spp. Porcine protegrins showed even greater activity against those
      organisms, as well as against anaerobic bacteria associated with adult
      periodontitis, including Porphyromonas gingivalis Prevotella intermedia and
      Fusobacterium nucleatum. Based on these observations, we believe that protegrin
      like beta-sheet peptide antibiotics may be useful dental therapeutics.

PMID- 9573498
TI  - Regional differences in the characteristics and treatment of patients
      participating in an international heart failure trial. The Assessment of
      Treatment with Lisinopril and Survival (ATLAS) Trial Investigators.
AB  - AIMS: This study was designed to determine regional differences in patient
      characteristics and medication use among patients entered into an international
      heart failure trial. METHODS AND RESULTS: Data for this analysis were derived
      from the Assessment of Treatment with Lisinopril and Survival Study (ATLAS), a
      prospective randomized comparison of high- and low-dose therapy with lisinopril
      in patients with New York Heart Association class II, III, or IV chronic heart
      failure, which enrolled 3164 patients in 291 centers in 19 countries on 3
      continents. Information was collected at baseline concerning patient
      demographics, etiology of heart failure, accompanying conditions, prior
      revascularization procedures, and medication use. The primary findings were a
      lower incidence of ischemic cardiomyopathy in southern and western Europe, more
      frequent diabetes in North America, and a greater use of coronary
      revascularization in the United States and Canada. There was substantial
      variation in medication use, particularly with regard to digoxin, anticoagulants,
      and amiodarone. CONCLUSIONS: Although there is considerable overlap in guidelines
      concerning the treatment of heart failure issued by authorities in Europe and
      North America, there are significant regional variations in medication use. Some,
      but not all, of these differences can be explained by differences in patient
      characteristics.

PMID- 9573499
TI  - Exercise-based rehabilitation improves skeletal muscle capacity, exercise
      tolerance, and quality of life in both women and men with chronic heart failure.
AB  - BACKGROUND: Data of training effects in chronic heart failure patients are based
      on findings in men. The purpose of this study was to compare the effects of
      skeletal muscle endurance training between men and women with chronic heart
      failure. METHODS AND RESULTS: Twelve consecutive men (mean [+/- SD] age 58 +/- 9
      years, left ventricular ejection fraction 29 +/- 9%) and 12 women (60 +/- 10
      years, left ventricular ejection fraction 28 +/- 7%) with moderate, chronic heart
      failure stratified according to age and inclusion criteria were investigated at
      baseline and after 8 weeks of knee extensor endurance training. The activity of
      skeletal muscle citrate synthase and resting heart rate were similar in men and
      women at baseline and with training improved (P < .0001) similarly in both
      genders. Peak work rate (P < .0001), peak oxygen uptake (P < .001) and muscle
      strength (P < .05) at baseline were higher in men than in women. Training
      improved peak work rate (P < .0001) and muscle strength (P < .0001) similarly in
      both genders, while improvement in peak oxygen uptake was better in women (P <
      .001). The distance ambulated during 6 minutes was similar in both genders at
      baseline and increased after training more in men (P < .004). The overall and
      physical Sickness Impact Profile indicated similarly reduced health-related
      quality of life in men and women, while worse psychosocial quality of life was
      observed in men (P < .05). Both genders improved after exercise training in the
      overall, physical, and psychosocial Sickness Impact Profile (P < .01).
      CONCLUSIONS: Exercise-based rehabilitation improves skeletal muscle capacity,
      exercise tolerance, and the health-related quality of life in women as well as in
      men with moderate, chronic heart failure.

PMID- 9573500
TI  - Predictors of myocardial dysfunction in human immunodeficiency virus-infected
      patients.
AB  - BACKGROUND: Some of the most frequent manifestations of heart involvement in
      human immunodeficiency virus (HIV) infection include right and left ventricular
      dysfunction. The pathogenesis remains obscure. METHODS AND RESULTS: This
      prospective clinical and echocardiographic study involved 181 patients at all
      stages of HIV infection. We tested a set of clinical variables using a backward
      logistic regression model to assess their ability to independently predict the
      presence of ventricular dysfunction. The presence of pulmonary infections (all
      etiologies mixed) was the only variable independently associated with isolated
      right ventricular dysfunction (odds ratio = 4.08; P = .02). Signs suggestive of
      pulmonary arterial hypertension were present in 71% of the patients with right
      ventricular dilation. History of previous opportunistic infections (all
      etiologies mixed) (odds ratio = 10.9; P = .0026) and time since the diagnosis of
      acquired immunodeficiency syndrome more than 12 months (odds ratio = 6.6; P =
      .03) were the only two independent predictors of left ventricular dysfunction.
      CONCLUSIONS: Isolated right ventricular dysfunction may be secondary to pulmonary
      hypertension caused by repetitive pulmonary infections and not to primary
      myocardial disease. The aggressive treatment of opportunistic infections may
      become an important element of heart failure prophylaxis in HIV infection because
      they may be associated with left ventricular dysfunction.

PMID- 9573501
TI  - Natural course of angiographic parameters after myocardial infarction: an
      evaluation in the prethrombolytic and pre-angiotensin converting enzyme
      inhibition era.
AB  - BACKGROUND: After myocardial infarction, left ventricular dilation is a frequent
      cause of cardiac insufficiency, which is associated with high morbidity and
      mortality. In this angiographic study, the natural course of postinfarction
      ventricular dilation could be followed up because patients undergoing
      revascularization procedures were excluded and only some few patients received
      angiotensin-converting enzyme inhibitors. METHODS AND RESULTS: Of 85 patients
      suffering from angina after myocardial infarction, 59 could be examined twice by
      angiocardiography in a mean interval of 52 +/- 14 months; 37 of the 59 patients
      had sustained posterior myocardial infarction, 20 had anterior myocardial
      infarction, and 2 had both. During follow-up, end-diastolic volume index
      increased from 100 +/- 27 mL/m2 to 110 +/- 34 mL/m2; in 26 of the 59 patients the
      increase was greater than 15 mL/m2. Irrespective of the time since infarction,
      patients with an end-diastolic volume index greater than 100 mL/m2 and an
      ejection fraction less than 50% at the time of first angiography were at high
      risk of progressive ventricular dilation and further deterioration of left
      ventricular function (for both, P = .003). This process was independent of extent
      of coronary artery involvement and coronary disease progression. Multivariate
      analysis identified ejection fraction at the time of index angiography as the
      strongest predictor of further left ventricular dilation (P = .0004).
      CONCLUSIONS: Continuing left ventricular dilation occurs in less than half the
      patients who had myocardial infarction. Left ventricular ejection fraction is the
      most sensitive parameter to predict the risk of ventricular dilation after
      infarction.

PMID- 9573502
TI  - Systemic hemodynamic, neurohormonal, and renal effects of a steady-state infusion
      of human brain natriuretic peptide in patients with hemodynamically decompensated
      heart failure.
AB  - BACKGROUND: Human brain natriuretic peptide (hBNP) is a promising agent for the
      treatment of decompensated cardiac failure. However, the systemic hemodynamic,
      neurohormonal, and renal effects of hBNP have been incompletely studied in human
      heart failure. METHODS AND RESULTS: The effects of a continuous 4-hour infusion
      of hBNP were determined in 16 decompensated heart failure patients in an
      invasive, randomized, double-blind, placebo-controlled study. Patients were
      evaluated during three 4-hour study periods: baseline, treatment (placebo [n = 4]
      versus hBNP 0.025 or 0.05 microgram/kg/min [n = 12]), and post-treatment. Urinary
      volume losses were replaced hourly to separate the vasodilatory and diuretic
      effects of hBNP. Two patients in the hBNP group were excluded from the analysis
      because of adverse events. hBNP significantly (P < .001) reduced right atrial
      pressure and pulmonary capillary wedge pressure by approximately 30% and 40%,
      respectively. hBNP also significantly lowered systemic vascular resistance from
      1722 +/- 139 to 1101 +/- 83 dynes.s.cm-5 (P < .05). These unloading effects of
      hBNP produced a 28% increase in cardiac index (P < .05) with no change in heart
      rate. Compared to placebo, hBNP decreased plasma norepinephrine and aldosterone.
      Renal hemodynamics were unaffected by hBNP; however, most patients were resistant
      to its natriuretic effect. CONCLUSIONS: 1) The predominant hemodynamic effects of
      hBNP were a decrease in cardiac preload and systemic vascular resistance. 2) hBNP
      also improved cardiac output without increasing heart rate. 3) Plasma
      norepinephrine and aldosterone levels decreased during hBNP infusion. 4) hBNP is
      pharmacologically active and has potential in the therapy for decompensated heart
      failure.

PMID- 9573504
TI  - Surgical approaches to arresting or reversing chronic remodeling of the failing
      heart.
AB  - Chronic ventricular remodeling is a central feature of heart failure that
      strongly correlates with a poor prognosis. Several recent surgical treatments for
      heart failure may derive benefit by their ability to arrest or substantially
      reverse this remodeling process. Dynamic cardiomyoplasty involves wrapping the
      heart with the latissimus dorsi muscle and stimulating the muscle to assist
      contraction. The wrap itself may provide a constraint helping to limit
      progressive cardiac dilation and/or assist in reversing this process. Left
      ventricular assist devices almost completely unload the heart and augment
      systemic circulation, thereby reducing neurohumoral activation. These combined
      effects seem to alter the chamber and cellular phenotype, and reversal of some
      molecular changes are associated with failure. Lastly, the partial
      ventriculectomy procedure directly reverses remodeling by acute removal of a
      portion of the lateral wall. Only preliminary nonrandomized trial data are
      currently available for each of these therapies with larger trials under way.
      However, early results are intriguing and are yielding insights into these
      mechanisms.

PMID- 9573503
TI  - Effect of left ventricular sphericity on the evolution of ventricular dysfunction
      in rats with diffuse isoproterenol-induced myocardial necrosis.
AB  - BACKGROUND: Previous studies in heart failure have suggested that increased left
      ventricular (LV) sphericity is a precursor to hemodynamic deterioration, although
      these studies have predominantly used models with segmental damage due to
      coronary vessel occlusion and have only made baseline assessments of LV function.
      The purpose of this study was to examine the relationship between LV geometry and
      hemodynamic compromise through time in heart failure due to graded, diffuse
      myocardial injury with a patent coronary circulation. METHODS AND RESULTS: Rats
      received two injections of either 0, 85, 170, or 340 mg/kg isoproterenol. At 2,
      6, and 16 weeks after injection, baseline hemodynamics, peak pressure-generating
      (aortic occlusion) and flow-generating (Tyrode's volume loading) capacities, and
      ventricular pressure-volume curves, dimensions, and histological scoring were
      measured. Increased LV sphericity preceded deterioration in baseline cardiac
      output, although it was the most powerful correlate of the dose-dependent
      decreases in peak cardiac output and ejection fraction. Time-dependent increases
      in pressure-generating capacity at a given volume were also due to compensatory
      increases in LV sphericity. The extent of right ventricular damage was also a
      strong correlate of peak flow-generating capacity. CONCLUSIONS: This study
      demonstrates that isoproterenol-induced myocardial necrosis resulted in
      progressive hemodynamic dysfunction of the left ventricle which most closely
      correlated with alterations in LV geometry. Although increases in LV sphericity
      preceded decrements in baseline function, techniques that assessed peak LV
      function demonstrated that increased LV sphericity was directly correlated with
      decreased peak flow-generating capacity, underscoring the clinical importance of
      these geometric alterations.

PMID- 9573505
TI  - Evolving concepts of heart failure: cooling furnace, malfunctioning pump,
      enlarging muscle. Part II: Hypertrophy and dilatation of the failing heart.

PMID- 9573506
TI  - A recent history of foot-and-mouth disease.

PMID- 9573507
TI  - Changes in lymphocyte subsets in the intestine and mesenteric lymph nodes in
      caprine paratuberculosis.
AB  - Changes in the number and distribution of lymphocyte subsets were investigated in
      the intestinal mucosa and mesenteric lymph nodes of three goats with natural
      paratuberculosis, comparisons being made with a single uninfected control animal.
      Lesions in the naturally infected goats varied from small granulomata with scarce
      epithelioid or multinucleated giant cells, containing few or no bacilli, in the
      intestine (tuberculoid type) to an extensive, diffuse epithelioid cell infiltrate
      containing numerous bacilli in the gut and mesenteric lymph nodes (lepromatous
      type). The number and distribution of lymphocyte subsets in the control were
      consistent with data reported from other non-infected goats. However, in the
      goats with paratuberculosis, significant changes were observed in the number and
      distribution of CD4+ and CD8+ T lymphocytes, the changes being related to the
      severity of the lesions. In the intestinal mucosa of the goat with tuberculoid
      lesions no significant changes were observed, but in the cortical area of
      mesenteric lymph nodes the number of CD4+ T lymphocytes decreased and the number
      of CD8+ T lymphocytes increased. In the two goats with lepromatous lesions, there
      was a decrease in the CD4+ T subpopulation and an increase of CD8+ T lymphocytes
      in the lamina propria of the intestine and particularly in the cortical area of
      the mesenteric lymph nodes, the CD4:CD8 ratio (< 1) being the opposite of that
      observed in healthy goats. Because of the small numbers of animals, further
      studies including additional animals are needed to confirm these preliminary
      results, which suggest that the progression of paratuberculous lesions may be due
      to an ineffective host immune response attributable to the CD8+ T lymphocyte
      subset that "downregulates" the activity of the CD4+ T lymphocytes required for
      macrophage activation.

PMID- 9573508
TI  - Metabolic findings in the erythrocytes of cardiopathic and anaemic dogs.
AB  - Few data are available on the activities of canine erythrocyte enzymes and on 2,3
      diphosphoglycerate (2,3DPG) concentrations in pathological conditions other than
      heritable erythrocyte defects. Because some diseases might affect erythrocyte
      metabolism and oxygen transport, we evaluated these parameters in 10 healthy dogs
      and in dogs with symptomless dirofilariosis (n = 9), mild (n = 13) and severe (n
      = 8) cardiac failure, and haemolytic anaemia (n = 8). To evaluate possible
      membrane damage, the osmotic fragility of the red cells was measured. No
      haematological abnormalities were found in the dogs with mild cardiopathy or in
      those with symptomless dirofilariosis. Severe anaemia and neutrophilic
      leucocytosis were found in the dogs with haemolytic anaemia and, to a lesser
      degree, in those with severe heart failure. In dogs with these two diseases,
      elevated values obtained were, respectively: pyruvate kinase (PK) 17.5 +/- 10.3
      U/g haemoglobin (Hb) (P < 0.001) and 11.6 +/- 7.5 U/g Hb (P < 0.01); glucose-6
      phosphate dehydrogenase (G6PDH) 8.9 +/- 5.4 U/g Hb (P < 0.001) and 5.6 +/- 4.2
      U/g Hb; 2,3DPG 21.8 +/- 4.9 U/g Hb (P < 0.001) and 22.5 +/- 4.1 U/g Hb (P <
      0.001). The increased 2,3DPG concentrations may have been due to diminished
      oxygen availability but the observed enzymatic changes were attributed mainly to
      the presence of young red blood cells: there was a positive correlation between
      nucleated red blood cells and PK activity, G6PDH activity and 2,3DPG
      concentration and a negative correlation between mature erythrocytes and PK
      activity, G6PDH activity and 2,3DPG concentration. This was supported by the
      derivative curve of the fragiligram, which showed two or three peaks
      corresponding to different erythrocyte populations and by the negative
      correlation between the maximum haemolytic NaCl concentration and the
      reticulocyte number. The measurement of PK and G6PDH activity and of the 2,3PG
      concentration, together with information provided by the fragiligram, would seem
      to be of value in defining the clinico-haematological picture in clinical heart
      diseases and haemolytic anaemia.

PMID- 9573509
TI  - Enthesopathy of the radial tuberosity in two thoroughbred racehorses.
AB  - Two cases of enthesopathy of the radial tuberosity in Thoroughbred racehorses are
      described. Soft X-ray pictures revealed separated bony fragments at the anterior
      aspect of the radial tuberosity, resembling the lesions of Osgood-Schlatter
      disease in children. Osgood-Schlatter lesions result from detachment of a portion
      of the apophysis of the tibial tuberosity. However, in the affected horses, the
      detached bony fragments consisted of cortical bone tissue composed of trabeculae
      with osteons similar to lamellar bone, the main component of the radial
      tuberosity. Tendon fibrils were inserted into the anterior parts of the detached
      fragments, and scar tissue filled the gap between the posterior part of the
      fragments and the radial tuberosity. The bone fragments may have originated from
      an avulsion fracture at the site of attachment of the tendinous portion of the
      biceps brachii muscle to the bone tissue of the radial tuberosity, a site at
      which high-tensile force is repeatedly exerted by muscle contraction.

PMID- 9573510
TI  - Naturally occurring mucoepidermoid carcinoma in the submandibular salivary gland
      of two mice.
AB  - Mucoepidermoid carcinomas in two mice were investigated histologically,
      immunohistochemically and ultrastructurally. The neoplastic cells showed
      divergent differentiation into periodic acid-Schiff-positive mucous cells,
      keratin-positive squamous cells, and cells with both mucous granules and sheaves
      of tonofilaments. Gland formation and keratinization were not observed. At the
      periphery of tumour cell nests, some cells were immunolabelled for smooth muscle
      actin or contained concentrated thin filaments, and these observations were
      interpreted to indicate that murine mucoepidermoid carcinomas are associated with
      both myoepithelium and duct epithelium.

PMID- 9573511
TI  - Fatal rupture of the brachiocephalic artery in a dog.
AB  - A case of arterial rupture that caused sudden death in a 3-year-old dog is
      presented. Rupture of the brachiocephalic artery was located just distal to the
      origin of the left common carotid artery. Histological examination of the vessel
      wall revealed necrosis of the media.

PMID- 9573512
TI  - Vascular leiomyoma of the mesentery in a dog.
AB  - A 4-year-old male, miniature Schnauzer dog showed two large masses in the
      mesentery at necropsy. Histological examination of both masses revealed plain
      smooth muscle tumour cells intermingled with thick-walled blood vessels. The
      bundles of tumour cells often extended from the periphery of the vessels. Mitotic
      figures were rare. From these findings, the tumour was diagnosed as a vascular
      leiomyoma (angiomyoma), previously unreported in animals. The term, vascular
      leiomyoma, was proposed to describe this tumour in order to avoid confusion with
      hamartomatous angiomyoma.

PMID- 9573513
TI  - Changes in the lungs of lambs after intratracheal injection of lipopolysaccharide
      from Pasteurella haemolytica A1.
AB  - Ten lambs aged 8 weeks were inoculated intratracheally through the tracheal wall
      with lipopolysaccharide from Pasteurella haemolytica A1 and examined in
      chronological sequence by light and electron microscopy for pulmonary lesions. An
      acute fibrinopurulent pneumonia was produced, which resolved within 72 h but bore
      many resemblances to field cases of pneumonic pasteurellosis. Sequestration of
      neutrophils in the capillaries of the lungs and aggregation of surfactant in the
      alveoli occurred rapidly, followed by swelling of the alveolar and capillary
      endothelia, oedema, haemorrhage, and emigration of neutrophils into the
      interstitium and small air spaces of the lungs. Necrosis of isolated neutrophils
      was a constant feature. Alveolar, interstitial and intravascular macrophages and
      lymphoid cells increased slowly to become the predominant inflammatory cells at
      72 h. A surprising feature was the transient appearance of multinucleated cells
      in the lungs at 2 and 6 h after inoculation. It is concluded that
      lipopolysaccharide makes a major contribution to the pathogenesis of P.
      haemolytica infection in the lungs of sheep.

PMID- 9573514
TI  - Hydrocephalus associated with Neospora caninum infection in an aborted bovine
      fetus.
AB  - This paper describes Neospora caninum-associated hydrocephalus in an aborted
      Hereford bovine fetus of 7 months' gestational age. Numerous tachyzoites were
      observed in areas of the cerebrum with lesions of non-suppurative necrotizing
      encephalitis.

PMID- 9573515
TI  - Personality disorder and dimension differences between type A and type B
      substance abusers.
AB  - Substance abuse subtype differences in DSM-IV personality disorders and normal
      personality dimensions were evaluated in 370 inpatient and outpatient alcohol,
      cocaine, and opiate abusers. The Type A/Type B distinction was replicated, with
      Type B substance abusers exhibiting more premorbid risk factors, more severe
      substance abuse, and greater psychosocial impairment. As predicted, compared to
      Type A, Type B were more commonly diagnosed with, and had more severe symptoms
      of, all personality disorders except Schizoid. With regard to normal personality
      dimensions, Type B scored higher on neuroticism, novelty seeking, and harm
      avoidance; Type A scored higher on agreeableness, conscientiousness,
      cooperativeness, and self-directedness. These subtype differences remained after
      controlling for the effects of antisocial personality and psychiatric symptoms.

PMID- 9573516
TI  - The persistence of borderline personality disorder in adolescence.
AB  - The stability of borderline personality disorder in adolescents is quite
      uncertain. To determine the persistence of the borderline personality disorder
      (BPD) and of separate borderline symptoms in adolescents, a follow-up study was
      conducted of hospitalized adolescents with (n = 14) and without (n = 22) BPD,
      according to the diagnostic interview for borderline patients (DIB). Of the 14
      borderline adolescents, only two cases were again classified as BPD after 3
      years, but some of the separate borderline symptoms were still present. In the
      nonborderline group, no new borderline cases were found after 3 years.

PMID- 9573517
TI  - Avoidant personality disorder: empirical support for DSM-IV revisions.
AB  - This article attempts to answer three questions about avoidant personality
      disorder (AVPD): (a) Is it a coherent unidimensional entity, (b) Is the
      requirement that four or more of the criteria be met in order to make the
      diagnosis justified, and (c) Are the changes made in DSM-IV supported? Four
      hundred thirty-four people presenting for treatment for anxiety were assessed
      with the Personality Disorder Examination. The criteria met were factor analyzed
      to indicate the unidimensionality of the diagnosis. Measures of internal
      consistency were calculated to validate the instruction to diagnose AVPD if four
      or more criteria were observed. Confirmatory factor analysis showed that a single
      factor was the best fit to the observed pattern of relationships between the
      seven AVPD criteria. The internal consistency of the seven criteria was moderate
      (Cronbach's alpha = .76) with a median intercriterion correlation of .29. The
      data provided good support for the hypothesis that the seven DSM-III-R AVPD
      criteria assess a single dimension. Three of the criteria did not reflect this
      factor as highly as the remaining four and these three have either been dropped
      in DSM-IV or substantially revised.

PMID- 9573519
TI  - Personality dimensions associated with depressive personality disorder.
AB  - Depressive personality disorder (DPD) is a historically important construct that
      requires empirical attention. This study compares 26 subjects with this disorder
      to 20 non-DPD subjects who have similar histories of longstanding early-onset
      depression on three personality measures, the Tridimensional Personality
      Questionnaire (TPQ), NEO-Five Factor Inventory, and Defense Style Questionnaire
      (DSQ). The samples were demographically similar and had similar rates of comorbid
      depression and dysthymia. They differed in that DPD subjects scored significantly
      higher on Harm Avoidance and Neuroticism, and significantly lower on Novelty
      Seeking, Extroversion, and Adaptive defense mechanisms. Implications for clinical
      care and nosology are discussed.

PMID- 9573518
TI  - Personality disorders and the five-factor model: a test of facet-level
      predictions.
AB  - We tested predicted relationships (Widiger, 1993; Widiger, Trull, Clarkin,
      Sanderson, & Costa, 1994) between personality disorder scores and facets of the
      five-factor model, and evaluated the relative benefits of facet-level analyses
      over domain-level analyses. Data from 614 undergraduates indicated: (a) 63% of
      the predicted facet relationships were significant, although many unpredicted
      relationships also emerged; (b) facet-level analyses did not yield substantially
      stronger effect sizes than domain-level analyses; but (c) facet-level analyses
      provided much better discrimination between personality disorders than domain
      level analyses. Facets of the openness to experience domain also helped
      discriminate between personality disorders, which is in contrast to previous
      domain-level findings that openness is not important.

PMID- 9573521
TI  - Gender differences in the relationship of antisocial personality disorder
      criteria to Psychopathy Checklist-Revised scores.
AB  - The relationship among adult, child, and full antisocial personality disorder
      (APD) criteria with the Psychopathy Checklist-Revised (PCL-R) (Hare, 1991)
      scores, an alternative to the Diagnostic and Statistical Manual of Mental
      Disorders' APD diagnosis, is examined in 395 men and 121 women substance abusers.
      Based on prior research, it was hypothesized that the correlations among
      childhood, adult, and full APD criteria and PCL-R Total, Factor 1 (Psychopathic
      Personality Traits), and Factor 2 (Antisocial Lifestyle) scores would differ for
      men and women. There was no difference between men and women in the correlations
      between full APD and PCL-R scores. Adult APD, however, had a stronger
      relationship to the Total and Factor 1 PCR-R scores in women compared to men,
      whereas child APD criteria were significantly related, although weakly, to Factor
      1 scores for men, but not for women.

PMID- 9573520
TI  - Field trial of a diagnostic axis for defense mechanisms for DSM-IV.
AB  - Following critiques that the DSM multiaxial system lacks psychodynamic
      information useful for treatment, an axis for defense mechanisms was developed
      for DSM-IV, including up to 7 individual defenses from a glossary of 27, and 3
      predominant defense levels from a list of 7. We tested the feasibility,
      reliability, and discriminability of the proposed axis. Clinician and psychiatric
      resident volunteers were trained at two U.S. and one Norwegian sites. After
      conducting initial interviews on 107 patients, they rated the DSM-III-R and
      defense axes, as did a second blind rater. Median kappa reliabilities were .42
      (individual defenses), and .47 (defense levels). A summary measure, Overall
      Defensive Functioning (ODF), had similar reliability to current GAF (IR .68 vs.
      .62), similar 1-month stability (.75 vs. .78), but greater 6-month stability (.51
      vs. .17). Independent of Axis III, ODF had small to moderate associations with
      other Axes and symptoms. Our findings indicate that the defense axis is a
      feasible, acceptably reliable, and nonredundant addition to DSM-IV, which may
      prove useful for planning and conducting treatment.

PMID- 9573522
TI  - Relationship of personality disorders to observer ratings of interpersonal style
      in forensic psychiatric patients.
AB  - Interpersonal theorists have conceptualised personality disorders as extreme
      styles defined by the interpersonal circle. Tests of this proposition have
      previously relied on self-report measures of interpersonal style. This study
      examined the relationships between observer ratings of interpersonal style (Chart
      of Interpersonal Reactions in Closed Living Environment [CIR-CLE]) and the
      personality disorder scales of the Millon Clinical Multiaxial Inventory (MCMI-I)
      in a sample of male forensic psychiatric inpatients (N = 104). Statistically
      significant interpersonal components were found for most personality disorder
      scales, but relationships were generally modest. The results are consistent with
      the view that the interpersonal circle provides a partial classification of
      personality disorders.

PMID- 9573523
TI  - The relationship between defense styles and personality disorders.
AB  - The relationships between personality disorder clusters and defense mechanism
      factors were evaluated in 31 female and 24 male psychiatric inpatients from an
      urban hospital, who ranged in age from 19 to 57 years. The degree to which
      defense factors predicted personality disorder psychopathology was assessed, with
      gender entered as a covariate. The degree of borderline psychopathology had the
      strongest relationship with the Immature defense style (F(1,54) = 9.83, R2 = .54,
      p < .05). The results support previous research demonstrating a stronger link
      between Borderline personality disorder and defense styles relative to other
      personality disorders.

PMID- 9573524
TI  - A critique of the overfill hypothesis of sodium and water retention in the
      nephrotic syndrome.
AB  - Recent reviews have claimed that the majority of patients with the nephrotic
      syndrome have plasma volume expansion (that is, they are overfilled). Here we
      attempt to re-establish balance to the debate on body fluid volume status in
      nephrotic patients by: (a) discussing the conflicting literature on plasma volume
      measurements in the nephrotic syndrome; (b) providing alternate explanations for
      data purporting to support an overfill hypothesis in the nephrotic syndrome; (c)
      emphasizing secondary neurohumoral responses that support underfilling at least
      as frequently as overfilling; and (d) emphasizing the clinical importance of
      fluid assessment in the individual patient with the nephrotic syndrome
      particularly in relation to diuretic use.

PMID- 9573525
TI  - Switching off renal inflammation by anti-inflammatory mediators: the facts, the
      promise and the hope.

PMID- 9573526
TI  - A novel frameshift mutation induced by an adenosine insertion in the polycystic
      kidney disease 2 (PKD2) gene.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
      Mendelian disorders and is genetically heterogeneous. Linkage studies have shown
      that the majority (approximately 85%) of ADPKD cases are due to mutations in PKD1
      on chromosome 16p13.3, while mutations in PKD2 on chromosome 4q21-q23 are thought
      to account for most of the remaining cases. In this report, we describe the
      mutation in a large four-generation ADPKD family (TOR-PKD77) which we had mapped
      to the PKD2 locus by linkage analysis. In this family, we screened for mutations
      by directly sequencing two nested RT-PCR fragments (PKD2N1 and PKD2N2) that cover
      approximately 90% of the PKD2 open reading frame. In the affected members, we
      identified a novel single adenosine insertion (2160InsA) in the PKD2N2 fragment.
      This mutation occurred in the polyadenosine tract (nt2152-2159) of exon 11 and is
      predicted to result in a frameshift with premature translation termination of the
      PKD2 product, polycystin 22, immediately after codon 723. The truncated
      polycystin 2 is predicted to lack the calcium-binding EF-hand domain and two
      cytoplasmic domains required for the homodimerization of polycystin 2 with itself
      and for the heterodimerization of polycystin 2 with polycystin 1.

PMID- 9573527
TI  - Atrial natriuretic peptide inhibits endothelin-1-induced activation of JNK in
      glomerular mesangial cells.
AB  - Atrial natriuretic peptide (ANP) has been shown to counteract various actions of
      endothelin-1 (ET-1) in mesangial cells. We have reported that both extracellular
      signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) are activated
      by ET-1 and ET-1-induced activation of ERK is inhibited by ANP. To further
      clarify the action of ANP, we examined the effect of ANP on ET-1-induced
      activation of JNK. ANP inhibited ET-1-induced activation of JNK in a dose
      dependent manner. This inhibitory effect of ANP was reversed by HS-142-1, an
      antagonist for biological receptors of ANP, while C-ANP, an analog specific to
      clearance receptors of ANP, failed to inhibit ET-1-induced activation of JNK. 8
      Bromo-cGMP and sodium nitroprusside were also able to inhibit ET-1-induced
      activation of JNK, suggesting cGMP-dependent action of ANP. In contrast, ANP
      failed to inhibit interleukin-1 beta (IL-1 beta)-induced activation of JNK. Since
      an increase in intracellular calcium ([Ca2+]i) was shown to be necessary for ET-1
      induced activation of JNK in mesangial cells, we measured [Ca2+]i using fura-2.
      ANP attenuated the ET-1-induced increase in [Ca2+]i in concentrations enough to
      inhibit ET-1-induced activation of JNK. Finally, ANP was able to inhibit ET-1-,
      but not IL-1 beta-induced increase in DNA-binding activity of AP-1 by gel shift
      assay. These results indicate that ANP is able to inhibit ET-1-induced activation
      of AP-1 by inhibiting both ERK and JNK, suggesting that ANP might be able to
      counteract the expression of AP-1-dependent genes induced by ET-1.

PMID- 9573528
TI  - C-type natriuretic peptide inhibits mesangial cell proliferation and matrix
      accumulation in vivo.
AB  - Local C-type natriuretic peptide (CNP) production and CNP receptor expression
      have been demonstrated in glomeruli. However, the glomerular (patho
      )physiological functions of CNP are largely unknown. We therefore investigated
      the effects of CNP on mesangial cell proliferation and matrix accumulation in the
      rat mesangioproliferative anti-Thy 1.1 model. Over seven days rats received a
      continuous infusion (1 microgram/kg/min) of either CNP (N = 6), an irrelevant
      control peptide (N = 3) or buffer alone (N = 6). Kidney biopsies were performed
      on days 2, 4 and 8. Few significant differences between the groups were noted on
      days 2 and 4. Compared to buffer treated rats on day 8, those receiving CNP
      showed a 35% reduction of glomerular mitoses, a 62% reduction of glomerular
      uptake of the thymidine analogue BrdU and a significant reduction in glomerular
      expression of PDGF B-chain. Double immunoperoxidase staining also revealed
      blunting of proliferating, activated mesangial cells (515 reduction of alpha
      smooth muscle actin-/BrdU-positive cells) and macrophage influx. Moreover, there
      was a marked reduction of mesangial collagen IV and fibronectin accumulation at
      the protein and mRNA level. Rats receiving the control peptide were
      indistinguishable from buffer treated rats. Systemic blood pressure was reduced
      by 10 to 20% in both CNP and control peptide treated rats on day 8, excluding
      that the findings were due to hemodynamic effects of CNP. Our findings
      demonstrate that CNP is involved in the regulation of mesangial cell
      proliferation and matrix production in vivo. The data suggest the existence of a
      glomerular natriuretic peptide system that may regulate tissue homeostasis and
      contribute to resolution of mesangioproliferative diseases.

PMID- 9573529
TI  - Interaction of IGF-I and 1 alpha, 25(OH)2D3 on receptor expression and growth
      stimulation in rat growth plate chondrocytes.
AB  - Growth plate cartilage cell express receptors for, and are affected by both IGF-I
      and 1 alpha, 25(OH)2D3. The studies were undertaken to investigate interaction
      between these two hormone systems, that is, (i) to study effects of 1 alpha,
      25(OH)2D3 on IGF-type 1 receptors (IGFIR), on IGF-I stimulated cell replication,
      colony formation, and on alkaline phosphatase activity (AP), and conversely, (ii)
      to study the effect of IGF-I on vitamin D receptor (VDR) expression on 1 alpha,
      25(OH)2D3 stimulated growth parameters and on AP activity. Freshly isolated rat
      tibial chondrocytes were grown in monolayer cultures, (serum-free) or in agarose
      stabilized suspension cultures (0.1% FCS). Vitamin D receptor and IGFIR were
      visualized by immunostaining with the monoclonal antibody (mAb) 9A7 gamma and mAb
      alpha IR3, respectively, and quantitated by RT-PCR for mRNA and by Scatchard
      analysis using [3H]-1,25(OH)2D3 and [125I]-alpha IR3. Cell proliferation was
      measured by [3H]-thymidine incorporation, growth curves in monolayer cultures,
      and by colony formation in agarose-stabilized suspension cultures. IGF-I dose
      dependently increased [3H]-thymidine incorporation. 1 alpha, 25(OH)2D3, but not 1
      beta, 25(OH)2D3 was stimulatory at low ((10-12 M) and slightly inhibitory at high
      (10-8 M) concentrations. The effect of IGF-I was additive to that of 1 alpha, 25
      (OH)2D3 [IGF-I 60 ng/ml, 181 +/- 12.7; 1 alpha, 25(OH)2D3 10(-12) M, 181 +/-
      9.8%, IGF-I + 1 alpha, 25(OH)2D3, 247 +/- 16.7%, P < 0.05 by ANOVA] and
      specifically obliterated by polyclonal IGF-I antibody (AB-1). Interaction could
      also be confirmed in suspension cultures. IGFIR mRNA and [125I]-alphaIR3 binding
      was increased by low (10(-12) m) but not by high (10(-8) M) concentrations of 1
      alpha, 25(OH)2D3. Homologous up-regulation by IGF-I (60 ng/ml) was specifically
      inhibited by AB-1 and markedly amplified by coincubation with 1 alpha, 25(OH)2D3
      (10(-12)m). Immunostaining with alpha IR3 showed specific IGFIR expression in rat
      growth cartilage, but not liver tissue. Stimulation of chondrocytes with 1 alpha,
      25(OH)2D3 or IGF-I suggested some increase of receptor expression in single
      cells, but the predominant effect was increased recruitment of receptor positive
      cells, Vitamin D receptor expression was markedly stimulated (fourfold) by IGF-I
      (60 ng/ml), but not IGF-II and inhibited by actinomycin D. This study shows that
      IGF-I and 1 alpha, 25(OH)2D3 mutually up-regulate their respective receptors in
      growth plate chondrocytes. In parallel, they have additive effects on cell
      proliferation and colony formation suggesting independent effector pathways.

PMID- 9573530
TI  - Heparin-binding epidermal growth factor-like growth factor in experimental models
      of membranous and minimal change nephropathy.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently
      described member of the epidermal growth factor (EGF) family. It binds to heparan
      sulfate proteoglycans via a cationic domain and is a potent mitogen for
      epithelial cells, fibroblasts and vascular smooth muscle cells. In the present
      study we have attempted to identify changes in quantity and distribution of HB
      EGF in two models of acute glomerular epithelial cell injury, using Western
      blotting, immunohistochemistry and in situ hybridization. Prior to disease
      induction, Western blots showed some expression of HB-EGF protein within
      glomeruli. Within the first three days in the acute puromycin aminonucleoside
      (PAN) and passive Heymann nephritis (PHN) models, immunohistochemistry and in
      situ hybridization demonstrated an up-regulation of HB-EGF mRNA and protein in
      glomerular epithelial cells (GEC). In both cases, increased protein and mRNA was
      found prior to the onset of proteinuria and continued until day 21 post
      induction, the last time point studied. Early in the course of the models, HB-EGF
      was localized to the cytoplasm of glomerular epithelial cells. At day 21,
      however, HB-EGF protein was distributed in a nodular pattern within GEC and along
      the glomerular basement membrane (GBM) in both models, suggesting that the
      secreted form might bind to the membrane. The increase in HB-EGF protein within
      glomeruli was confirmed by Western blots of glomerular membrane protein which,
      however, demonstrated a single 29 kDa species, consistent with the transmembrane
      form. These data are not consistent with binding of the secreted form of HB-EGF
      to the GBM. The transmembrane form of HB-EGF is able to signal in a juxtracrine
      fashion, so increased expression of HB-EGF mRNA and protein by GEC might
      contribute to the genesis of proteinuria through the initiation of abortive GEC
      mitogenesis.

PMID- 9573531
TI  - DNA binding of activator protein-1 is increased in human mesangial cells cultured
      in high glucose concentrations.
AB  - Human mesangial cells (HMC) grown in high glucose environments synthesize
      excessive amounts of extracellular matrix proteins (ECM). The promoter regions of
      certain ECM genes contain TPA (phorbol ester)-responsive element (TRE) motifs
      that bind the transcription factor, activator protein-1 (AP-1), a complex of Jun
      and other phosphoproteins. AP-1 binding to the TRE promoter is regulated by the
      quantity, composition and post-translational modifications of proteins in the AP
      1 complex. We report an increased binding of AP-1 to TRE oligonucleotides in HMC
      cultured chronically (5 days) in high glucose environments (30 mM d-glucose).
      This increased binding is not due to differences in the nuclear quantity of AP-1
      proteins or in the composition of the AP-1 complex when compared to AP-1 proteins
      from cells grown in normal glucose (5 mM d-glucose). A 30 mM l-glucose
      environment also increased AP-1 binding, but to a degree less than d-glucose. The
      increased AP-1 binding was partly reversed by treatment of HMC with Calphostin C
      or Bisindolylmaleimide I suggesting a partial role of the protein kinase C (PKC)
      pathway in mediating AP-1 binding. AP-1 binding was unaffected by treatment of
      cells with the MEK inhibitor PD 98059. In addition, increased AP-1 binding
      persisted for at least 48 hours after media glucose concentrations were
      normalized. The level of Jun-NH2-terminal kinase (JNK) activity and the
      phosphorylation of the JNK kinase, SEK1, were unchanged by chronic high glucose
      concentrations. These studies suggest that in HMC cultured in chronic high
      glucose, post-translational modifications increase the binding of AP-1 to the TRE
      motif.

PMID- 9573532
TI  - Interstitial fibrosis in hypercholesterolemic rats: role of oxidation, matrix
      synthesis, and proteolytic cascades.
AB  - Uninephrectomized rats with diet-induced hypercholesterolemia develop
      interstitial inflammation and fibrosis after 8 to 12 weeks. Fibrosis has been
      associated with the accumulation of lipid peroxidation products within the
      tubulointerstitium, along with increased renal mRNA levels for transforming
      growth factor beta-1 (TCF-beta 1), some matrix proteins, and the tissue inhibitor
      of metalloproteinases (TIMP-1). However, mRNA levels for urokinase-type
      plasminogen activator (uPA) have been found to be decreased. The purpose of the
      present study was to determine whether antioxidant therapy could attenuate
      interstitial fibrosis in hypercholesterolemic rats and to determine changes in
      the pattern of renal gene expression induced by antioxidant therapy. Three groups
      of uninephrectomized rats were studied after 12 weeks of feeding standard rat
      chow, an atherogenic diet (standard chow plus 4% cholesterol/1% cholic acid), or
      an atherogenic diet supplemented with high doses of the antioxidants probucol and
      vitamin E. Rats fed the atherogenic diet developed hypercholesterolemia and a 56%
      increase in total kidney collagen compared with rats fed standard chow. In
      comparison, the hypercholesterolemic rats treated with antioxidants had normal
      levels of renal lipid peroxidation products and a normal kidney collagen content.
      In contrast, there were no significant differences in urinary albumin excretion
      rates or the number of interstitial macrophages between the two
      hypercholesterolemic groups. Compared with the untreated hypercholesterolemic
      group, antioxidant therapy induced significant reductions in renal mRNA levels
      for procollagen III (to 60% of untreated levels), collagen IV (60%), and TIMP-1
      (20%), while uPA levels were significantly increased (to 210%). Paradoxically,
      antioxidant therapy was associated with a significant increase in renal TGF-beta
      1 mRNA levels (to 150%), although TGF-beta 1 protein expression shifted from
      interstitial to tubular epithelial cells in predominance. The results of the
      present study demonstrate the efficiency of antioxidant therapy in preventing
      renal interstitial fibrosis in hypercholesterolemic rats with a single kidney.
      Based on changes in renal gene expression at the mRNA level, impaired matrix
      protein synthesis and increased intrarenal activity of the metalloproteinases and
      uPA/plasmin may play a role in the attenuation of fibrosis.

PMID- 9573533
TI  - Clinicopathological significance of intratubular giant macrophages in progressive
      glomerulonephritis.
AB  - Very large macrophages, which we have termed "giant macrophages" (G-M phi), have
      been found in renal tubules, some containing cytoplasmic vacuoles. To elucidate
      their pathophysiological roles, we examined renal biopsy tissues from various
      primary glomerulonephritis (GN) and tubulointerstitial nephritis (TIN) using
      immunohistochemistry with monoclonal antibodies against M phi and other cell
      surface markers. Giant macrophages were absent or rare in TIN, minimal change
      nephrotic syndrome, and minor glomerular abnormalities, but G-M phi was plentiful
      in progressive glomerulonephrides such as IgA nephropathy with crescents,
      membranoproliferative GN, focal segmental glomerulosclerosis, and especially in
      crescentic GN. These G-M phi were usually seen in the lumen of renal tubules, but
      occasionally were found in the Bowman's spaces and glomerular tufts, and similar
      cells were also found in urine. Moreover, they frequently made contact with
      tubular epithelial cells expressing intercellular adhesion molecule-1, and the
      tubular epithelial cells in such lesions often had degenerative changes. Giant M
      phi may damage tubular epithelial cells from the luminal side. Phenotypically, G
      M phi showed activated (CD71+) and mature (25F9+) characteristics along with
      features of M phi (CD68+), and the cytoplasm contained a great deal of lipids.
      The numbers of G-M phi in renal tissues closely correlated with the degree of
      hematuria (rho = 0.5, P < 0.001), serum creatinine value (r = 0.63, P < 0.001) in
      GN patients (N = 96) and with proteinuria in IgA nephropathy patients (r = 0.89,
      P < 0.001, N = 27). These data suggest that G-M phi are M phi that were activated
      and matured in certain active inflammatory sites, which flowed into tubules and
      then into urine. Thus, the existence of G-M phi in biopsy tissue or urine reflect
      the activity of GN and may have a predictive value for the progression of GN.

PMID- 9573535
TI  - Urinary protein excretion rate is the best independent predictor of ESRF in non
      diabetic proteinuric chronic nephropathies. "Gruppo Italiano di Studi
      Epidemiologici in Nefrologia" (GISEN).
AB  - We investigated the predictors of the rate of glomerular filtration rate decline
      (delta GFR) and progression to end-stage renal failure (ESRF) in the 352 patients
      with proteinuric non-diabetic chronic nephropathies [urinary protein excretion
      rate (UProt) > or = 1 g/24 hr, creatinine clearance 20 to 70 ml/min/1.73 m2]
      enrolled in the Ramipril Efficacy In Nephropathy (REIN) study. Overall the GFR
      declined linearly by 0.46 +/- 0.05 ml/min/1.73 m2/month (mean rate +/- SEM) over
      a median follow-up of 23 months (range 3 to 64 months), and progression to ESRF
      was 17.3%. Using multivariate analysis, higher UProt and mean arterial pressure
      (MAP) independently correlated with a faster delta GFR (P = 0.0001 and P =
      0.0002, respectively) and progression to ESRF (P = 0.0001 and P = 0.003,
      respectively). Mean UProt and systolic blood pressure during follow-up were the
      only time-dependent covariates that significantly correlated with delta GFR (P =
      0.005 and P = 0.003, respectively) and ESRF (P = 0.006 and P = 0.0001,
      respectively). After stratification for baseline UProt, patients in the lowest
      tertile (UProt < 1.9 g/24 hr) had the slowest delta GFR (0.16 +/- 0.07
      ml/min/1.73 m2/month) and progression to ESRF (4.3%) as compared with patients in
      the middle tertile (UProt 2.0 to 3.8 g/24hr; delta GFR, 0.55 +/- 0.09 ml/min/1.73
      m2/month, P = 0.0002; ESRF, 15.3%, P = 0.0001) and in the highest tertile (UProt
      3.9 to 18.8 g/24 hr; delta GFR, 0.70 +/- 0.11 ml/min/1.73 m2/month, P = 0.0001;
      ESRF, 32.5%, P = 0.0001). Both delta GFR (P = 0.01) and progression to ESRF (P =
      0.01) significantly differed even between the middle and the highest tertiles. On
      the contrary, stratification in tertiles of baseline MAP failed to segregate
      subgroups of patients into different risk levels. Patients with the highest
      proteinuria and blood pressure were those with the fastest progression (delta
      GFR, 0.91 +/- 0.23; ESRF 34.7%). Of interest, at each level of baseline MAP, a
      higher proteinuria was associated with a faster delta GFR and progression to
      ESRF. On the other hand, at each level of proteinuria, a faster delta GFR was
      associated with MAP only in the highest tertile (> 112 mm Hg) and the risk of
      ESRF was independent of the MAP. Thus, in chronic nephropathies proteinuria is
      the best independent predictor of both disease progression and ESRF. Arterial
      hypertension may contribute to the acceleration of renal injury associated with
      enhanced traffic of plasma proteins. Antihypertensive drugs that most effectively
      limit protein traffic at comparable levels of blood pressure are those that most
      effectively slow disease progression and delay or prevent ESRF in proteinuric
      chronic nephropathies.

PMID- 9573534
TI  - Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis
      in rats.
AB  - ONO-5046 is a potent, specific and intravenously active inhibitor of neutrophil
      elastase. To examine the role of elastase in glomerulonephritis, we tested the
      effects of ONO-5046 on nephrotoxic serum (NTS) nephritis in a rat model of the
      disease in humans. Rats were administered ONO-5046 or phosphate-buffered saline
      (PBS) intraperitoneally 24 hours prior to injection of NTS, and they were then
      given equal doses of ONO-5046 or PBS three hours and 1, 2, 3, 4, 5 and 6 days
      later. Compared with the control groups, ONO-5046 significantly reduced
      proteinuria and hematuria, and suppressed the formation of crescentic glomeruli
      in a dose-dependent manner. Our results suggest that neutrophil elastase
      participates in NTS nephritis by degrading glomerular basement membrane proteins,
      and that the elastase inhibitor, ONO-5046, suppresses crescentic formation and
      glomerular injury caused by elastase.

PMID- 9573536
TI  - Infection of human primary renal epithelial cells with HIV-1 from children with
      HIV-associated nephropathy.
AB  - Children affected with human immunodefficiency virus (HIV)-associated nephropathy
      (HIVAN) usually develop significant renal glomerular and tubular epithelial cell
      injury. The pathogenesis of these changes is not clearly understood. Human renal
      tubular epithelial cells (RTEc) do not express CD4 surface receptors, and it is
      not clear whether these cells can be infected by HIV-1. Certain strains of HIV-1,
      however, have been shown capable of infecting CD4-negative epithelial cell lines.
      We hypothesized that the inability of laboratory strains of HIV-1 to infect renal
      epithelial cells may be due to a limited tropism, as opposed to wild-type viruses
      derived from children with HIVAN, and that viruses derived from these children
      are capable of infecting RTEc from the same patient. Here, we have demonstrated
      that HIV-1 isolates from children with HIVAN can productively infect RTEc through
      a CD4 independent pathway, and that infected mononuclear cells can transfer the
      virus to human RTEc. Human RTEc sustained low levels of viral replication and HIV
      1 inhibited the growth and survival of cultured human RTEc. Thus, HIV-1 may
      directly induce degenerative changes in RTEc of children with HIVAN. Infected
      macrophages may play a relevant role in this process by transferring viruses to
      RTEc.

PMID- 9573537
TI  - Clinical evaluation of a capture ELISA for detection of proteinase-3
      antineutrophil cytoplasmic antibody.
AB  - Detection of antineutrophil cytoplasmic antibodies (ANCA) has become a useful
      tool in the diagnosis of Wegener's granulomatosis and microscopic polyangiitis.
      However, the results obtained with indirect immunofluorescence (IIF) and by ELISA
      for ANCA demonstration do not always correlate. A possible explanation for this
      finding could be that proteins are denatured during the process of antigen
      purification or during coating onto the solid phase. To avoid this possibility, a
      monoclonal antibody to PR3 that is precoated on the plate can be used. In the
      present study we have used the monoclonal antibody (MoAb) 4A3 for the capture of
      PR3 in an ELISA, and a clinical evaluation of the diagnostic properties of the
      new capture ELISA has been made. The sensitivity of the capture PR3-ANCA ELISA
      was 85% in a material of c-ANCA positive sera. A specificity of 90% was obtained
      in analyses from patients having various forms of glomerulonephritis. There was a
      significantly higher diagnostic sensitivity of the capture PR3-ANCA ELISA (85%)
      compared to c-ANCA by IIF (58%) in patients with Wegener's granulomatosis with
      renal involvement. Capture PR3-ANCA and direct ELISA for MPO-ANCA together gave a
      diagnostic sensitivity of 98%, versus 75% using IIF. In conclusion, the capture
      PR3-ANCA ELISA seems to be a valuable tool in the diagnosis of Wegener's
      granulomatosis with renal involvement. Preliminary data suggest that the
      technique may have an advantage over direct ELISA for PR3-ANCA, as well as in the
      follow-up of c-/PR3-ANCA associated vasculitides. However, further prospective
      studies are needed to clarify this premise.

PMID- 9573538
TI  - High glucose concentration causes a rise in [Ca2+]i of cardiac myocytes.
AB  - Diabetes mellitus is associated with an elevation in the basal levels of
      cytosolic calcium ([Ca2+]i) of cardiac myocytes. This may be due in part to a
      glucose-induced elevation in [Ca2+]i. The present study examined this issue and
      explored the cellular pathways responsible for such a phenomenon. A total of 30
      mM glucose, mannitol or choline chloride, but not urea, induced a time- and dose
      dependent rise in the [Ca2+]i of cardiac myocytes. G protein inhibition by GDP
      beta S or pertussis toxin produced significant inhibition (> or = 80%) in the
      rise in [Ca2+]i. Incubation of cardiac myocytes in a calcium free medium or in
      media containing verapamil, nifedipine or amlodipine almost completely abolished
      the rise in [CA2+], while ryanodine produced only small reduction (10%) in the
      glucose-induced rise in [Ca2+]i. Rp-cAMP or H-89, inhibitors of the cAMP-protein
      kinase A pathway, produced a modest decrease in the rise in [Ca2+]i, while
      staurosporine (an inhibitor of PKC) and HOE 694 (an inhibitor of the Na(+)-H+
      exchanger) had no effect on the rise in [Ca2+]i. The results indicate that the
      osmotic activity of glucose (cell shrinkage) activates G protein(s), most likely
      through a stretch receptor, which in turn stimulates calcium channels inhibitable
      by verapamil, nifedipine and amlodipine, thus permitting a calcium influx into
      the cardiac myocytes. The increased calcium entry may stimulate a calcium release
      from intracellular stores by a calcium-induced calcium release process. Thus, in
      cardiac myocytes direct activation of calcium channels, and to a small extent
      activation of the cAMP-protein kinase A, and calcium-induced calcium release
      mediate the high glucose-induced acute rise in their [Ca2+]i.

PMID- 9573539
TI  - Impaired aquaporin and urea transporter expression in rats with adriamycin
      induced nephrotic syndrome.
AB  - Nephrotic syndrome is associated with abnormal regulation of renal water
      excretion. To investigate the role of collecting duct water channels and solute
      transporters in this process, we have carried out semiquantitative immunoblotting
      of kidney tissues from rats with adriamycin-induced nephrotic syndrome. These
      experiments demonstrated that adriamycin-induced nephrotic syndrome is associated
      with marked decreases in expression of aquaporin-2, aquaporin-3, aquaporin-4, and
      the vasopressin-regulated urea transporter in renal inner medulla, indicative of
      a suppression of the capacity for water and urea absorption by the inner
      medullary collecting duct. In contrast, expression of the alpha(1)-subunit of the
      Na,K-ATPase in the inner medulla was unaltered. Light and electron microscopy of
      perfusion-fixed kidneys demonstrated that the collecting ducts are
      morphologically normal and unobstructed. Inner medullary expression of the
      descending limb water channel, aquaporin-1, was not significantly altered,
      pointing to a selective effect on the collecting duct. Aquaporin-2 and aquaporin
      3 expression was also markedly diminished in the renal cortex, indicating that
      the effect is not limited to the inner medullary collecting duct. Differential
      centrifugation studies and immunocytochemistry in inner medullary thin sections
      demonstrated increased targeting of aquaporin-2 to the plasma membrane,
      consistent with the expected short-term action of vasopressin on aquaporin-2
      trafficking. The extensive down-regulation of aquaporin and urea transporter
      expression may represent an appropriate renal response to the extracellular
      volume expansion observed in nephrotic syndrome, but may occur at the expense of
      decreased urinary concentrating and diluting capacity.

PMID- 9573540
TI  - Effects of thyroid hormone on the neonatal renal cortical Na+/H+ antiporter.
AB  - The neonatal proximal tubule has a lower rate of bicarbonate absorption than that
      of adults. This is due, in part, to a lower rate of apical membrane Na+/H+
      antiporter activity. The purpose of these studies was to examine if thyroid
      hormone could be a factor in the maturational increase in Na+/H+ antiporter
      activity. Hypothyroid (0.01% propylthiouracil in drinking water starting at day
      14 gestation and throughout the postnatal period), euthyroid, and hyperthyroid
      (intraperitoneal triiodothyronine, 10 micrograms/100 g body wt, once daily on
      days 17 to 20 of postnatal life) rats were all studied at 21 days of life. Renal
      cortical brush border Na+/H+ antiporter activity was 453 +/- 24, 527 +/- 30 and
      608 +/- 25 pmol/mg protein in the hypothyroid, euthyroid and hyperthyroid groups,
      respectively (P < 0.001). Hyperthyroid neonates had approximately twofold greater
      renal cortical NHE-3 mRNA abundance than euthyroid and hypothyroid neonates (P <
      0.05). Brush border membrane NHE-3 protein abundance in hypothyroid and
      hyperthyroid neonates was one-third and twofold that of euthyroid 21-day-old
      rats, respectively (P < 0.001). These data are consistent with a potential role
      of thyroid hormone in the postnatal increase in Na+/H+ antiporter activity.

PMID- 9573542
TI  - Polarized distribution of Na+/H+ exchanger isoforms in rabbit collecting duct
      cells.
AB  - The present study describes two Na+/H+ exchanger (NHE) isoforms in an
      immortalized rabbit renal cortical collecting tubule cell line (RC.SV3). Na+/H+
      exchange activity was assayed using fluorescence measurements of intracellular pH
      (pHi) in monolayers mounted in a cuvette containing two fluid compartments,
      making it possible to independently measure Na+/H+ exchange activity on either
      the apical or basolateral surface. RC.SV3 monolayers express Na+/H+ exchange
      activities in both the apical and basolateral membrane domains. The two
      exchangers have half-saturation constants (Km) for external sodium and
      sensitivities to dimethylamiloride, to HOE-694 and to cimetidine and clonidine
      consistant with the NHE-1 isoform on the basolateral cell surface and the NHE-2
      isoform on the apical surface. Protein kinase A inhibition of basolateral
      exchanger activity was significantly higher than that of the apical exchanger.
      Protein kinase C significantly stimulated both exchangers equally. RT-PCR
      analysis found RNA for only NHE-1 and NHE-2, and immunofluorescence with an
      antibody against NHE-1 demonstrated a basolateral location for this isoform. The
      results suggest that RC.SV3 cells have two Na+/H+ exchange activities separated
      spatially to the two cellular membranes, with the NHE-1 and the NHE-2 isoforms
      located on the basolateral and the apical membranes, respectively.

PMID- 9573541
TI  - Erythropoietin receptor-operated Ca2+ channels: activation by phospholipase C
      gamma 1.
AB  - Erythropoietin (EPO) increases Ca2+ influx in vascular smooth muscle cells and
      acts both as a direct vasoconstrictor and vascular growth factor (that is,
      angiogenesis). However, the mechanism by which EPO promotes extracellular Ca2+
      entry in contractile cells has not been elucidated. In hematopoietic cells, EPO
      induces tyrosine kinase (TK)-dependent activation of phospholipase C (PLC)-gamma
      1 and Ca2+ influx via a voltage-independent Ca2+ conductance. In contractile
      mesangial cells, we have recently characterized a voltage-independent, 1 pS Ca2+
      channel that is dependent on both TK and PLC-gamma 1 activity. Therefore, we
      examined cultured rat glomerular mesangial cells after timed exposure to
      recombinant human EPO (20 U/ml). Erythropoietin increased the tyrosine
      phosphorylation of PLC-gamma 1, promoted membrane complex formation between PLC
      gamma 1 and the EPO receptor itself, and raised the levels of intracellular
      inositol 1,4,5-trisphosphate and intracellular Ca2+. Consistent with our previous
      studies, 1 pS Ca2+ channel activity was extremely low under basal, unstimulated
      conditions in cell-attached patches, but was dramatically increased when EPO was
      present in the patch pipette. Tyrosine kinase inhibition with 100 micron
      genistein or 1 micron PP1 (Src; selective tyrosine kinase inhibitor) prevented
      all of these EPO-induced responses. We conclude that: (1) EPO-induced stimulation
      of 1 pS Ca2+ channels is mediated via a cytosolic Src TK in glomerular mesangial
      cells. (2) Stimulation of this Ca2(+)-activated, Ca2(+)-permeable channel is
      dependent on the tyrosine phosphorylation/activation of PLC-gamma 1. (3) This
      cascade provides a possible mechanism for the vasoconstriction and hypertension
      observed with clinical EPO use for the treatment of chronic anemias.

PMID- 9573543
TI  - Expression of glucose transporters in human peritoneal mesothelial cells.
AB  - Glucose containing solutions, the basis of peritoneal dialysis fluids, affect the
      proliferation and regeneration of peritoneal mesothelial cells (MsC). The aim of
      this study was to examine mechanisms of glucose transport into MsC, that is, the
      expression of facilitative glucose transporters (GLUT) and the Na(+)-dependent
      glucose transporter (SGLT1) in human primary MsC and a transfected MsC line.
      Since expression of both transporters is differentiation dependent, we
      investigated the effects of cell differentiation induced by culturing MsC on
      membranes or by addition of hexamethylene bisacetamide (HMBA; 6 mM), which
      enhances SGLT1 expression in LLC-PK1 cells. Levels of mRNA for GLUT1 through
      GLUT4 and SGLT1 were evaluated by reverse transcriptase-polymerase chain reaction
      (RT-PCR). The presence of the corresponding proteins was examined by Western
      blotting and localized by immunofluorescence. Active, Na(+)-dependent glucose
      transport was assessed by alpha-methyl-D-[14C]glucopyranoside (AMG) with and
      without the SGLT1-specific inhibitor phlorizin and by patch clamp experiments in
      NaCl or choline-chloride, For Na(+) dependent glucose uptake choline chloride
      instead of NaCl served as negative control. Facilitative transport was assessed
      using 2-fluoro-2-deoxy-[14C]-D-glucose (FDG) with and without the inhibitors
      cytochalasin B or phloretin. Primary and transfected MsC express GLUT1 and GLUT3
      mRNA while no transcripts were found for GLUT2 and GLUT4. No SGLT1 transcript was
      detectable in subconfluent cells. Semiquantitative RT-PCR analysis documented
      that the addition of the differentiation inducer HMBA to confluent cultures or
      growth of MsC on membranes for seven days produced a down-regulation of mRNA for
      GLUT1, no change for GLUT3, and a substantial increase for SGLT1 mRNA. Under
      these conditions MsC express SGLT1 protein and possess a Na(+)-dependent glucose
      uptake as assessed by AMG. Phlorizin (1 mM) inhibits AMG uptake by 30 to 40%. In
      patch clamp experiments the addition of extracellular glucose depolarized the
      membrane potential only in the presence of sodium. These results indicate that
      differentiated MsC express GLUT1, GLUT3, and SGLT1. Further characterization of
      these transport mechanisms and their regulation may help to understand the
      cellular effects of glucose on MsC in peritoneal dialysis.

PMID- 9573544
TI  - Regulation of renal phosphate transport by acute and chronic metabolic acidosis
      in the rat.
AB  - Metabolic acidosis results in impaired renal tubular phosphate reabsorption and
      proximal tubular apical brush border membrane (BBM) sodium gradient-dependent
      phosphate transport (Na/Pi cotransport) activity. In the present study we
      investigated the cellular mechanisms responsible for decreased Na/Pi cotransport
      activity following six hours to 10 days of metabolic acidosis induced by
      ingestion of NH4Cl. Urinary Pi excretion was significantly increased and BBM
      Na/Pi cotransport activity was progressively and significantly decreased by 18%
      at six hours, 24% at 12 hours, 32% at 24 hours, and 61% after 10 days of
      metabolic acidosis. The progressive and time-dependent decreases in BBM
      cotransport activity were associated with progressive decreases in BBM NaPi-2
      protein (43% at 12 hr, 54% at 24 hr and 66% at 10 days) and cortical NaPi-2 mRNA
      (22% at 12 hr, 54% at 24 hr and 56% at 10 days) abundance. Interestingly,
      following six hours of metabolic acidosis, there was a significant 29% decrease
      in BBM NaPi-2 protein abundance that was not associated with decreases in either
      cortical homogenate NaPi-2 protein or cortical NaPi-2 mRNA abundance. In
      additional studies we found that the effects of chronic metabolic acidosis on
      Na/Pi cotransport activity were independent of endogenous parathyroid hormone
      activity, but were somewhat dependent on dietary Pi intake. In rats fed a high or
      a normal Pi diet metabolic acidosis caused significant decreases in Na/Pi
      cotransport activity, NaPi-2 protein and NaPi-2 mRNA abundance, however, in rats
      fed a low Pi diet the inhibitory effect of metabolic acidosis on Na/Pi
      cotransport were minimal and not significant. These results indicate that in
      chronic (> or = 12 hr) metabolic acidosis the progressive decrease in BBM Na/Pi
      cotransport activity is most likely mediated by decrease in BBM NaPi-2 protein
      and cortical mRNA abundance. In contrast, in acute (< or = 6 hr) metabolic
      acidosis the decrease in BBM Na/Pi cotransport activity is likely mediated by
      changes in the trafficking of the NaPi-2 protein that is, enhanced
      internalization from and/or impaired delivery of the NaPi-2 protein to the apical
      BBM.

PMID- 9573545
TI  - Salt intake determines the renal response to L-arginine infusion in normal human
      subjects.
AB  - Studies in experimental animals have shown that nitric oxide (NO) generation in
      the kidney from L-arginine participates in adapting renal function to changes in
      salt intake, but similar studies in human subjects are lacking. Therefore, we
      compared the infusion of 30 g of L-arginine to 30 g of branched chain amino acids
      (control), in eight normal human subjects after 5 to 7 days of equilibration to a
      low salt (LS; 20 mumol.24 hr-1) or high salt (HS; 200 mumol.24 hr-1) intake.
      Lithium clearance was used as a marker of proximal tubular reabsorption. Compared
      to the control infusion, L-arginine did not significantly alter blood pressure,
      inulin or paraaminohippurate clearance, but significantly increased (P < 0.05)
      the excretion of NO2 + NO3 (NOx) (LS, 157 +/- 46 to 210 +/- 48 mumol.min-1; HS,
      138 +/- 30 to 182 +/- 70) and cGMP (LS, 253 +/- 63 to 337 +/- 76 pmol.min-1; HS,
      311 +/- 68 to 563 +/- 52). Renal sodium excretion was decreased by L-arginine
      infusion during the low salt intake (45 +/- 5 to 21 +/- 3 mumol.min-1; P < 0.05)
      but was increased by L-arginine during the high salt intake (298 +/- 56 to 537 +/
      84 mumol.min-1; P < 0.05). The calculated fractional reabsorption of sodium in
      the proximal and distal nephrons, as assessed from lithium and sodium clearances,
      was increased by L-arginine during the low salt intake but was decreased by L
      arginine during the high salt intake. L-arginine increased plasma insulin
      concentration significantly (P < 0.05). This effect was independent of salt
      intake (LS, 67 +/- 7 to 92 +/- 13 ng.ml-1; HS, 66 +/- 7 to 76 +/- 9 ng.ml-1). L
      arginine did not significantly after plasma renin activity. In conclusion, L
      arginine increases the excretion of NOx and cGMP and increases plasma insulin,
      but the effect on sodium excretion depends upon salt intake. L-arginine enhances
      Na reabsorption in the proximal and distal nephrons during the low salt intake,
      but inhibits it during the high salt intake. Effects of L-arginine on NO and cGMP
      may contribute to its effects on Na reabsorption.

PMID- 9573546
TI  - Human kallikrein gene delivery protects against gentamycin-induced nephrotoxicity
      in rats.
AB  - The tissue kallikrein-kinin system has been shown to play important roles in
      cardiovascular and renal function. The aim of this study was to investigate
      potential protective effects of kallikrein gene delivery in gentamycin-induced
      nephrotoxicity. Rats were injected subcutaneously with gentamycin daily for 10 to
      14 days. Adenovirus, Ad.CMV-cHK carrying the human tissue kallikrein gene or
      Ad.CMV-LacZ carrying the beta-galactosidase gene under the control of the
      cytomegalovirus promoter, were delivered intravenously on the first day of
      gentamycin administration. The expression of human tissue kallikrein mRNA was
      identified in the kidney, aorta, heart and liver and immunoreactive human
      kallikrein levels were measured in the serum and urine of rats receiving
      kallikrein gene delivery. Adenovirus-mediated kallikrein gene delivery
      significantly increased the renal blood flow, glomerular filtration rates, and
      urine flow while it attenuated renal tubular damage, cellular necrosis, lumenal
      protein casts and reduced ventricular weight and cardiomyocyte size. Kallikrein
      gene delivery caused a decrease in blood urea nitrogen levels and increases in
      urinary kinin and nitrite/nitrate levels. This study shows that kallikrein gene
      delivery exhibits protection against gentamycin-induced nephrotoxicity, and
      raises the potential for kallikrein gene therapy to treat drug-induced renal
      diseases.

PMID- 9573547
TI  - Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of
      rat.
AB  - Prostacyclin (PGI2) is known to have a relaxative action on vascular smooth
      muscle, an inhibitory action against platelet activation and neutrophil function.
      Previous studies showed the preventive effects of PGI2 on lupus nephritis and Thy
      1 nephritis, although the mechanism has not been clarified. Glomerular
      endothelial expression of intercellular adhesion molecule-1 (ICAM-1) is up
      regulated in experimental and human glomerular diseases, and is known to
      facilitate leukocyte infiltration into the glomeruli, which ultimately induces
      the various glomerular injuries. In the present study, we evaluated the
      therapeutic effects of PGI2 on a rat model for crescentic glomerulonephritis and
      investigated its putative mechanism in relation to ICAM-1-mediated leukocyte
      recruitment. Wistar-Kyoto (WKY) rats were injected with nephrotoxic serum and
      received continuous intraperitoneal infusion of PGI2. PGI2 dramatically decreased
      proteinuria (123.0 +/- 18.8 vs. 31.6 +/- 4.5), crescent formation and deposition
      of fibrinogen in the glomeruli, while the deposition of rabbit IgG, rat IgG and
      rat C3 along the capillary walls was not changed. Furthermore, intraglomerular
      expression of ICAM-1 and infiltration of macrophages were significantly
      suppressed by administration with PGI2. In contrast, influx of CD4 or CD8
      positive cells was not altered. The present results suggest that PGI2 shows the
      preventive effects on experimental crescentic glomerulonephritis by inhibiting
      intraglomerular coagulation and ICAM-1-mediated macrophage-glomerular endothelial
      cell adhesive pathway.

PMID- 9573548
TI  - Down-regulation of Fc alpha receptors on blood cells of IgA nephropathy patients:
      evidence for a negative regulatory role of serum IgA.
AB  - IgA nephropathy (IgAN) is associated with increased serum IgA1 and IgA1-immune
      complexes (IC). As Fc alpha receptors (Fc alpha R) are candidate molecules to
      regulate IgA levels, increased receptor occupation by IgA1 prompted us to study
      the expression of Fc alpha R on blood cells of IgAN patients. Surface and
      cytoplasmic Fc alpha R expression were markedly decreased on monocytes, despite
      normal levels of transcripts. Fc alpha R expression on patients' neutrophils was
      slightly decreased, exclusively at the cell surface. However, when autologous
      plasma was removed from the cells Fc alpha R was up-regulated. This observation
      led us to search for circulating regulatory factors. In vitro experiments
      revealed that Fc alpha R was down-regulated on normal monocytes following long
      term culture with control or patient purified serum IgA at high concentrations (5
      mg/ml). Moreover, polymeric myeloma IgA1 induced stronger down-regulation than
      monomeric IgA1. These results point to a negative regulatory role of serum IgA on
      surface Fc alpha R expression. This is also supported by a negative correlation
      between levels of Fc alpha F on blood cells and serum IgA. On the other hand,
      endogenous IgA bound to IgAN cells was significantly higher than IgA bound to
      control cells pre-incubated with patients' plasma, suggesting abnormalities in
      the receptor-ligand interaction. Patient Fc alpha R had a higher Mr (60 to 85
      kDa) than those of controls (55 to 75 kDa) and a decreased binding to a sialic
      acid-specific lectin on blots, indicating post-translational modifications with
      impaired sialylation of surface Fc alpha R molecules that might be involved in
      enhanced IgA binding. Continuous Fc alpha R occupation by IgA, associated with
      receptor down-regulation, might contribute to the enhancement of circulating IgA1
      and IgA1-IC by impairing their binding and degradation. Finally, increased
      receptor occupation by IgA on monocytes was linked to mesangial proliferation and
      glomerular sclerosis, suggesting a role for IgA-bound cells in the pathogenesis
      of mesangial damage.

PMID- 9573549
TI  - Apo(a)-isoform size, nutritional status and inflammatory markers in chronic renal
      failure.
AB  - Atherosclerotic cardiovascular disease and malnutrition are widely recognized as
      leading causes of the increased morbidity and mortality observed in uremic
      patients. Levels of lipoprotein (a) [Lp(a)], an established cardiovascular risk
      factor, are elevated in uremic patients. Moreover, low serum albumin levels
      indicating malnutrition have been associated with elevated plasma Lp(a) levels in
      dialysis patients. However, serum albumin levels are also influenced by an
      inflammatory reaction. The present study was undertaken to further investigate
      the relationship between Lp(a), inflammation and malnutrition in patients with
      chronic renal failure (CRF) prior to the initiation of renal replacement therapy,
      and to investigate the potential relation between these factors and apo(a)
      isoform size, an important determinant of plasma Lp(a) levels. A total of 83
      patients (mean age 52 +/- 1 year) with terminal (creatinine clearance 9 +/- 1
      ml/min) CRF were cross sectionally investigated. In addition to lipid parameters
      and apo(a)-isoform size, C-reactive protein (CRP), nutritional parameters
      including serum levels of albumin and body composition (dual energy x-ray
      absorptiometry), as well as a subjective global assessment (SGA) and the
      prevalence of cardiovascular disease (CVD) were evaluated. Malnourished patients
      (N = 39) had a significantly (P < 0.05) higher median plasma Lp(a) level (19.5
      mg/dl) as compared to 44 well-nourished patients, (11.7 mg/dl). No difference was
      found for other lipid or lipoprotein parameters. A significant relationship was
      found between CRP and plasma Lp(a), whereas no significant relation was observed
      between plasma Lp(a) and serum albumin levels. The apo(a)-isoform distribution
      was similar among malnourished and well-nourished patients. There was no
      difference in nutritional parameters when comparing patients with small- and
      large-size apo(a) isoforms. However, a subgroup of patients (12%) with no
      detectable apo(a)-bands and low Lp(a) levels had significantly higher lean body
      mass. The present study demonstrates elevated plasma Lp(a) levels in CRF patients
      with signs of malnutrition, even though no direct relationships between plasma
      Lp(a) levels and various nutritional parameters were observed. The observed
      relationship between Lp(a) and CRP suggests that inflammatory factors, more
      prevalent in patients with malnutrition, may contribute to the Lp(a) increase in
      malnourished CRF.

PMID- 9573550
TI  - Insulin resistance and hyperinsulinemia are already present in patients with
      incipient renal disease.
AB  - In uremic patients resistance to the action of insulin has been documented, but
      it is not known at what stage of renal disease it appears. We therefore examined
      29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult
      polycystic kidney disease (ADPKD) in different stages of renal failure, and in
      addition, healthy age-matched subjects. Insulin sensitivity and other variables
      of glucose metabolism were assessed using a frequent sampling intravenous glucose
      tolerance test (minimal-model technique). Glomerular filtration rate (GFR) was
      assessed in renal patients using the inulin-clearance technique. Mean insulin
      sensitivity index (SI), that is, insulin sensitivity, was significantly lower (P
      < 0.001) in all patients combined than in matched healthy subjects (N = 16; 14
      males, mean age 42 +/- 3 years; mean SI 8.6 +/- 0.8 min-1 uU/ml). The mean SI was
      not significantly different in patients with renal disease of immune (IgAGN) or
      non-immune (ADPKD) origin, and it was not correlated with GFR (r = 0.01, P <
      0.52), intact PTH (r = -0.23, P < 0.11) or calcitriol concentration (r = -0.03, P
      < 0.82). Consequently, the mean SI was similar in renal patients with GFR within
      the normal range (N = 19; 17 males, mean age 41 +/- 2 years; mean GFR 119 +/- 5
      ml/min/1.73 m2; 5.1 +/- 0.7 min-1 uU/ml), in patients with mild to moderate renal
      failure (N = 16; 15 males, 46 +/- 3 years; 67 +/- 4 ml/min/1.73 m2; 5.1 +/- 0.7
      min-1 microU/ml) and in patients with advanced renal failure (N = 15; 13 males,
      46 +/- 3 years; 25 +/- 2 ml/min/1.73 m2; 4.7 +/- 0.6 min-1 uU/ml). Mean fasted
      plasma insulin concentration, the area under the curve for plasma insulin
      concentration (AUC) and total insulin delivery (TID) during the glucose tolerance
      test were significantly higher in patients than in healthy subjects, reflecting
      hyperinsulinemia in renal patients. Further, fasted plasma insulin concentration
      (r = -0.32, P < 0.009), AUC (r = -0.62, P < 0.0001) and TID (r = -0.34, P <
      0.004) in patients were significantly correlated with insulin sensitivity (SI).
      The present data document that insulin resistance and concomitant
      hyperinsulinemia are present early in the course of renal disease, that is, even
      in patients with GFR within the normal range, irrespective of the type of renal
      disease. This observation may have potential implications with respect to the
      high cardiovascular morbidity and mortality in patients with renal disease.

PMID- 9573551
TI  - Simultaneous determination of oxalate, citrate and sulfate in children's plasma
      with ion chromatography.
AB  - To improve our understanding of both diagnosis and treatment of diseases of
      oxalate metabolism, we first set out to establish a new ion-chromatographic
      method to determine normal plasma levels of oxalate, citrate and sulfate from
      single plasma samples. In 50 infants and children (23 girls, 27 boys, aged 0.2 to
      17 years) with normal renal function, blood was drawn in Li-heparin tubes, placed
      on ice and preserved immediately with 40 microliters M HCl/ml plasma in two
      ultracentrifugation steps. For measurement, plasma was injected onto an ion
      chromatography system with NaOH as the mobile phase, and then run as a linear
      gradient from 5 mM to 52.5 mM over 21 minutes. Analysis yielded measurable and
      reproducible oxalate (6.43 +/- 1.06 microM/liter), citrate (79.3 +/- 27.4
      microM/liter) and sulfate (235.0 +/- 85.3 microM/liter) levels, without any age
      and gender specific differences. The least detectable plasma oxalate level was <
      0.3 microM with a high reliability and reproducibility (coefficient of variance
      1.95 to 4.75%). In conclusion, we established a reproducible, precise method to
      determine the relevant plasma anions involved in mineral metabolism, which
      heretofore have not been easily measurable. Studies of diseases of oxalate and
      citrate metabolism are ongoing on the basis of the normal plasma values achieved
      in this study.

PMID- 9573552
TI  - 1,25-Dihydroxyvitamin D3 corrects insulin and lipid abnormalities in uremia.
AB  - The effect of intravenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] therapy on
      insulin and lipid metabolism was examined in patients on maintenance hemodialysis
      (HD). Eight patients (Group I, 19 +/- 1 years old) were studied before and after
      four weeks of intravenous 1,25 (OH)2D3 therapy (1.8 +/- 0.3 micrograms), during
      which time the serum parathyroid hormone (PTH) concentrations did not change.
      Another eight patients (Group II, 18 +/- 1 years old) were studied before and
      after four weeks of oral dihydrotachysterol (0.8 +/- 0.1 mg). Serum PTH also did
      not change in Group II. Serum glucose concentrations during an oral glucose
      tolerance test (OGTT) were higher in Group I before 1,25(OH)2D3 compared with
      controls and these normalized following four weeks of intravenous 1,25(OH)2D3.
      Serum glucose concentrations during OGTT were also higher in Group II before DHT
      compared with controls and did not change following four weeks of oral DHT.
      Insulin sensitivity during euglycemic clamp studies in Group I before 1,25(OH)2D3
      (223 +/- 20 mg/m2/min; P < 0.01) was low compared with controls (320 +/- 26
      mg/m2/min) and was normalized following therapy (315 +/- 25 mg/m2/min). Insulin
      sensitivity was also low in Group II at the beginning of the study and did not
      change at the end of the four week period. Both early-phase and late-phase
      insulin secretion were low in Group I before 1,25(OH)2D3 compared with controls
      and normalized following intravenous 1,25(OH)2D3 therapy. Both early-phase and
      late-phase insulin secretion were also low in Group II at the beginning of the
      study and did not change at the end of the four week period of DHT treatment.
      Plasma triglycerides were elevated in Group I patients before treatment (198 +/-
      16 mg/dl; P < 0.01) compared with controls (139 +/- 12 mg/dl) and were normalized
      (148 +/- 13 mg/dl) following intravenous 1,25(OH)2D3 therapy. Plasma total
      cholesterol and high density lipoprotein cholesterol were normal before treatment
      compared with controls and did not change following Intravenous 1,25(OH)2D3
      therapy. Plasma triglycerides, total cholesterol and high density lipoprotein
      cholesterol did not change in Group II during the study period. Thus, intravenous
      1,25(OH)2D3 therapy corrected glucose intolerance, insulin resistance,
      hypoinsulinemia as well as hypertriglyceridemia in patients on HD, in the absence
      of PTH suppression.

PMID- 9573553
TI  - Bone disease in children and adolescents undergoing successful renal
      transplantation.
AB  - Little is known about the extent and severity of bone disease in children
      undergoing successful renal transplantation. To address this issue, 47 patients
      with stable renal function 3.2 +/- 1.7 years after transplantation (Tx) underwent
      iliac crest bone biopsy. The mean age of patients was 12 +/- 2.0 years; 36 had
      received cadaveric renal grafts, whereas 11 had undergone living-related Tx.
      Immunosuppressive drugs included cyclosporine 0.17 +/- 0.4 mg/kg/day, prednisone
      7.5 +/- 2.1 mg/kg/day, and either azathioprine 1.6 +/- 0.9 mg/kg/day or
      mycophenolate mofetil 30 +/- 3 mg/kg/day. In addition to quantitative bone
      histomorphometry, the bone mineral content (BMC) of the lumbar spine was measured
      by dual energy X-ray absorptiometry (DXA) in 24/47 patients. Thirty-one
      transplant recipients had normal bone formation (N-Bfr), 11 had mild
      hyperparathyroidism (HPT) and 5 had adynamic skeletal lesions (AD). The interval
      since Tx, duration of dialysis before Tx and cumulative prednisone dose did not
      differ among groups. Trabecular bone area was highest in subjects with HPT.
      Unexpectedly, eroded bone perimeter exceeded normal reference values both in
      patients with AD and in those with N-Bfr; the osteoid area and osteoid perimeter
      were also elevated in these two groups. Hyperparathyroidism improved or resolved
      after Tx in all 14 subjects with this skeletal lesion prior to Tx, but one
      patient developed AD after Tx. Bone histology did not change after Tx in those
      with N-Bfr during regular dialysis, but bone formation increased after Tx in two
      of three patients with AD during regular dialysis. Z-scores for height in pre
      pubertal patients after Tx were below age-appropriate values in each histologic
      subgroup, but values did not differ among groups. Z-scores for bone mineral
      content at the lumbar spine were also less than age-predicted values, -0.67 +/-
      1.2. After adjusting for the degree of growth retardation, height-adjusted z
      scores for lumbar spine BMC after Tx were above normal in all three histologic
      groups (0.68 +/- 1.0). The results suggest that reductions in bone mass and post
      transplant osteoporosis are not prominent findings in pediatric renal transplant
      recipients when the influence of growth retardation on bone mass measurements by
      DXA is carefully considered.

PMID- 9573554
TI  - Beta 2-microglobulin modified with advanced glycation end products modulates
      collagen synthesis by human fibroblasts.
AB  - Beta 2-microglobulin amyloidosis (A beta 2m) is a serious complication for
      patients undergoing long-term dialysis. beta 2-microglobulin modified with
      advanced glycation end products (beta 2m-AGE) is a major component of the amyloid
      in A beta 2m. It is not completely understood whether beta 2m-AGE plays an active
      role in the pathogenesis of A beta 2m, or if its presence is a secondary event of
      the disease. beta 2-microglobulin amyloid is mainly located in tendon and osteo
      articular structures that are rich in collagen, and local fibroblasts constitute
      the principal cell population in the synthesis and metabolism of collagen. Recent
      identification of AGE binding proteins on human fibroblasts lead to the
      hypothesis that the fibroblast may be a target for the biological action of beta
      2m-AGE. The present study demonstrated that two human fibroblast cell lines
      exhibited a decrease in procollagen type I mRNA and type I collagen synthesis
      after exposure to beta 2m-AGE for 72 hours. Similar results were observed using
      AGE-modified albumin. Antibody against the RAGE, the receptor for AGE, attenuated
      this decrease in synthesis, indicating that the response was partially mediated
      by RAGE. In addition, antibody against epidermal growth factor (EGF) attenuated
      the decrease in type I procollagen mRNA and type I collagen induced by beta 2m
      AGE, suggesting that EGF acts as an intermediate factor. These findings support
      the hypothesis that beta 2m-AGE actively participates in connective tissue and
      bone remodeling via a pathway involving fibroblast RAGE, and at least one
      interposed mediator, the growth factor EGF.

PMID- 9573555
TI  - Effects of hepatitis C infection and renal transplantation on survival in end
      stage renal disease. The New England Organ Bank Hepatitis C Study Group.
AB  - Hepatitis C virus (HCV) infection is common among patients with end-stage renal
      disease (ESRD). However, the effect of HCV infection on survival among ESRD
      patients, and the impact of renal transplantation on the course of HCV infection
      has not been adequately defined. Sera from patients on the renal transplant
      waiting list at the New England Organ Bank between November 1986 and June 1990
      were tested for anti-HCV using a third generation ELISA. All anti-HCV positive
      patients and a 1:1 ratio of randomly selected anti-HCV negative patients
      comprised the study sample. Duration of follow-up was calculated from the date of
      the first available serum specimen until death, loss to follow-up or December 31,
      1995, whichever occurred earlier. Multivariate analysis of risk factors for
      mortality was performed using a Cox proportional hazards model which included
      anti-HCV as a time-independent (baseline) variable, transplantation as a time
      dependent (follow-up) variable, and independently significant baseline
      covariates. Anti-HCV was detected in 287 (19%) of 1544 patients in whom sera were
      available, and 286 anti-HCV negative patients served as controls. Complete
      information was available in 496 (87%) of these 573 patients. Median follow-up
      was 73 months (range 1 to 110 months), during which time 302 (61%) patients
      underwent renal transplantation and 154 (31%) patients died. For anti-HCV
      positive patients compared to anti-HCV negative patients, the relative risk of
      death (and 95% confidence intervals) from all causes was 1.41 (1.01 to 1.97) and
      due to liver disease or infection was 2.39 (1.28 to 4.48). For patients who
      underwent transplantation compared to those who remained on dialysis, the
      relative risk of death from all causes between 0 to 3 months, 3 to 6 months,
      seven months to four years, and after four years was 4.75 (2.76 to 8.17), 1.76
      (0.75 to 4.13), 0.31 (0.18 to 0.54) and 0.84 (0.51 to 1.37), respectively. There
      was no interaction between the effect of anti-HCV status as baseline and
      subsequent transplantation (P = 0.93), meaning that the association between
      treatment modality and survival was similar among anti-HCV positive and negative
      patients, at all intervals after transplantation. We conclude that HCV infection
      at the time of referral for transplantation is associated with an increased risk
      of death, irrespective of whether patients remain on dialysis or undergo
      transplantation. Transplantation has a beneficial rather than adverse effect on
      long-term survival in anti-HCV positive patients. Hence, anti-HCV positive status
      alone is not a contraindication for renal transplantation.

PMID- 9573556
TI  - Hemodialysis stimulates hepatocyte growth factor release.
AB  - Studies were performed in 26 patients on regular dialysis treatment with
      cuprophane (CU), polymethylmetacrilate (PMMA) or cuprammonium (CAM) dialyzers.
      Controls were six patients with chronic renal failure but not on regular dialysis
      treatment (CRF) and six healthy subjects (N). Blood was collected at the start
      (T0), and at 15 (T15) and 240 (T240) minutes of dialysis to measure the serum
      hepatocyte growth factor (HGF) concentration and to study HGF production by
      peripheral blood mononuclear cells (PBMC) in vitro. The form of HGF (that is,
      inactive/monomeric, active/dimeric) present in the serum was analyzed by
      immunoblotting. In addition, the ability of serum to stimulate proliferation of
      tubular cells (HK-2) and HGF release by PBMC and fibroblasts (MRC-5) was
      investigated. At T0, serum HGF levels were identical to that of the controls. In
      patients treated with CU, serum HGF rose from 0.24 ng/ml at T0 to 7.44 ng/ml at
      T15, and remained high at T240. PBMC collected at T15 and T240 released
      significantly more HGF in vitro than those collected at T0. Serum at T15
      stimulated proliferation of HK-2 cells and the release of HGF by PBMC and MRC-5
      cells. The PMMA and CAM dialyzers had similar effects as the CU. These results
      indicate that dialysis induces a striking rise in serum HGF and a prompt
      circulation of factor(s) stimulating HGF release. Dialysis-activated PBMC release
      HGF.

PMID- 9573557
TI  - Differential response of glomerular epithelial and mesangial cells after subtotal
      nephrectomy.
AB  - Recent studies in both human and experimental chronic renal disease suggest that
      there is a linkage between glomerular hypertrophy and glomerulosclerosis. To
      further define these relationships, we studied the changes in glomerular
      hypertrophy, procollagen alpha 1(IV) mRNA levels and glomerulosclerosis in rats
      undergoing 1 2/3 nephrectomy (Nx) or sham nephrectomy (SNx). Glomerular
      hypertrophy, measured biochemically by RNA/DNA and protein/DNA ratios, was
      significantly increased in Nx compared to SNx two days after subtotal renal
      ablation (RNA/DNA: Nx = 133 +/- 8%, SNx = 100 +/- 3% of the mean control value, P
      < 0.01; protein/DNA: Nx = 164 +/- 22%, SNx = 100 +/- 10%, P < 0.05) and remained
      elevated after 7 and 15 days (RNA/DNA: seven days Nx = 155 +/- 3%, SNx = 100 +/-
      13%, P < 0.01; 15 days Nx = 303 +/- 21%, SNx = 100 +/- 24%, P < 0.001;
      protein/DNA: seven days Nx = 228 +/- 57%, SNx = 100 +/- 18%, P < 0.05; 15 days Nx
      = 341 +/- 23%, SNx = 100 +/- 18%, P < 0.01). Light microscopic measures of
      glomerular tuft volume (GTV) were too insensitive to detect glomerular
      enlargement until 15 days postoperatively, but GTV measured ultrastructurally
      demonstrated a 20% increment in Nx compared to SNx as early as two days
      postoperatively (P < 0.01). The latter increment in GTV was due exclusively to
      glomerular visceral epithelial cell (GVEC) expansion. Glomerular procollagen
      alpha 1(IV) mRNA levels were significantly elevated only 15 days after
      nephrectomy (Nx = 265 +/- 58% of the mean control value, SNx = 100 +/- 12%, P <
      0.05; corrected for beta-actin mRNA levels). As this time, exuberant mesangial
      expansion measured ultrastructurally contributed to a 1.6 +/- 0.1-fold increase
      in GTV (P < 10(-5)), and to a relative decrement in the GVEC contribution to
      glomerular cells plus matrix (P < 0.01). Segmental sclerosis was observed only 15
      days postoperatively in Nx (Nx = 1.3 +/- 0.4% of glomeruli evaluated, SNx = 0.0%,
      P < 0.05), and there was a strong correlation between the prevalence of segmental
      sclerosis and the procollagen alpha 1(IV) mRNA levels in Nx at 15 days (r = 0.93,
      P < 0.01). There was no significant correlation between the RNA/DNA and
      protein/DNA ratios and procollagen alpha 1(IV) mRNA levels. Thus, glomerular
      regions responded differentially to subtotal nephrectomy. Early epithelial cell
      expansion was followed by later mesangial expansion. Glomerular procollagen alpha
      1(IV) mRNA levels were elevated only during the second (mesangial) phase of
      glomerular hypertrophy, when it correlated with glomerulosclerosis, but not
      during the initial (epithelial) phase, a pattern consistent with a mesangial
      origin of the procollagen alpha 1(IV) mRNA.

PMID- 9573558
TI  - Control of serum phosphate without any phosphate binders in patients treated with
      nocturnal hemodialysis.
AB  - We compared the efficacy and the long-term effects of nocturnal hemodialysis
      (NHD) versus conventional hemodialysis (CHD) in controlling serum phosphate
      levels in patients with end-stage renal disease (ESRD). Patients underwent thrice
      weekly CHD and were subsequently switched to NHD six nights weekly. In the
      "acute" study serum and dialysate phosphate were measured during and after
      dialysis, and the total dialysate was collected to calculate mass solute removal.
      Although pre-dialysis (1.7 +/- 0.6 vs. 1.5 +/- 0.8 mM) serum phosphate levels
      were similar in CHD and NHD, respectively, post-dialysis levels were slightly
      lower with CHD (0.7 +/- 0.2 vs. 0.8 +/- 0.2 mM, P < 0.05). The measured phosphate
      removed per session of CHD or NHD was comparable, 25.3 +/- 7.5 versus 26.9 +/-
      9.8 mumol/session, respectively. On the other hand, the cumulative weekly
      phosphate removal was significantly higher with NHD as compared to CHD, 75.8 +/-
      22.5 versus 161.6 +/- 59.0 mumol/week (P < 0.01). In the "chronic" study serum
      phosphate levels were measured monthly for five months on CHD and for five months
      after the patients were switched to NHD. Dietary phosphate intake and the dosage
      of phosphate binders were tabulated. Serum phosphate levels fell during NHD: 2.1
      +/- 0.5 mM at the beginning of the study and 1.3 +/- 0.2 mM five months after
      being switched to NHD (P < 0.001). At the same time dietary phosphate intake
      increased by 50%. By the fourth month of NHD therapy none of the patients was
      taking any phosphate binders. In conclusion, NHD is more effective in controlling
      serum phosphate levels than CHD, allowing patients to discontinue their phosphate
      binders completely and to ingest a more liberal diet.

PMID- 9573559
TI  - Peritoneal urea and creatinine clearances in continuous peritoneal dialysis
      patients with different types of peritoneal solute transport.
AB  - We studied whether anuric subjects on continuous ambulatory peritoneal dialysis
      (CAPD) who achieve the target Kt/V urea of 2.0 weekly will also achieve the
      target normalized creatinine clearance (NCCr) of 60 liter/1.73 m2 weekly, and the
      reasons of discrepancy between the two clearances in anuric subjects, by
      analyzing 476 clearance studies performed in 309 CAPD patients within 12 months
      of the performance of a peritoneal equilibration test (PET). On the basis of the
      PET, peritoneal solute transport was classified as low (37 clearance studies),
      low-average (199 studies), high-average (186 studies) and high (54 studies). We
      found that weekly values of Kt/V urea in the low transport group (LTG) was 1.74
      +/- 0.51, in the low-average transport group (LATG) was 1.66 +/- 0.41, in the
      high-average transport group (HATG) 1.68 +/- 0.41, and in the high transport
      group (HTG) 1.73 +/- 0.46 (NS, variance analysis). Weekly values for NCCr,
      liter/1.73 m2 were: LTG, 37.8 +/- 9.0; LATG, 44.0 +/- 9.2; HATG, 49.2 +/- 10.0;
      HTG 56.8 +/- 13.3 (P < 0.0001). The ratios of raw (not-normalized) peritoneal
      creatinine clearance to peritoneal urea clearance were: LTG, 0.65 +/- 0.14; LATG,
      0.76 +/- 0.09; HATG, 0.84 +/- 0.09; HTG, 0.91 +/- 0.12 (P < 0.0001). Linear
      regression with Kt/V urea as x and NCcr as y revealed the following results: LTG,
      y = 19.486 + 10.500x, r = 0.591 [if x = 2.0, y = 15.004 + confidence interval
      (95% CI) of y 25.3 to 55.7]; LATG, y = 15.0004 + 17.482x, r = 0.774 (if x = 2.0,
      y = 50.0, 95% CI of y 38.4 to 61.6); HATG, y = 15.285 + 20.162x, r = 0.829 (if x
      = 2.0, y = 55.6, 95% CI of y 44.4 to 66.8); HTG, y = 14.945 + 24.134x, r = 0.839
      (if x = 2.0, y = 63.2, 95% CI of y 48.4 to 78.1). Peritoneal solute transport
      type has a major effect on peritoneal creatinine clearance, but an insignificant
      effect on peritoneal urea clearance. Consequently, the majority of anuric
      patients who achieve a weekly Kt/V urea of 2.0 will have a weekly NC cr lower
      than 60 liter/1.73 m2 and will require a Kt/V urea much higher than 2.0 to
      achieve the target NCcr of 60 liter/1.73 m2 weekly. The current targets of urea
      and creatinine clearance are not compatible in anuric patients on CAPD.

PMID- 9573560
TI  - Crystalluria: a clinically useful investigation in children with primary
      hyperoxaluria post-transplantation.
AB  - Primary hyperoxaluria type I (PH I) is a congenital error of metabolism that can
      be manifested by an increased oxalate production, and ultimately result in kidney
      failure. After a combined liver/kidney transplantation, children with PH I have
      persistent excretion of oxalate that causes crystal formation in the urinary
      tract, and could result in systemic oxalosis and eventual graft failure. We
      speculated that crystalluria may be predictive of this nephrolithogenic tendency
      and thus investigated the effect of an intensive therapeutic strategy to prevent
      crystal formation in 13 children at our hospital. Oxalate crystal volume (OCV)
      measurements were performed at regular intervals for 36 months, and compared with
      urine supersaturation measurements. We found that crystalluria with the OCV
      measurement is non-invasive, easily performed, and gives feedback on the efficacy
      of PH I therapy within one hour. Further study is needed to determine whether
      this method is a better predictor of nephrocalcinosis than is supersaturation
      alone.

PMID- 9573561
TI  - Water channels in health and disease.

PMID- 9573562
TI  - Hepatitis C and renal transplantation: the controversy continues.

PMID- 9573563
TI  - Fibrillary glomerulopathy.

PMID- 9573564
TI  - Does the ob gene product leptin stimulate erythropoiesis in patients with chronic
      renal failure?

PMID- 9573565
TI  - Critical care nephrology: the time has come.

PMID- 9573566
TI  - The critically ill patient.

PMID- 9573567
TI  - Acute renal failure: definition and pathogenesis.
AB  - Acute renal failure (ARF) in the critical care setting is defined as the abrupt
      decline in glomerular filtration rate (GFR) resulting from ischemic or toxic
      injury to the kidney. ARF is often only one of several organ-system failures that
      are present in this patient population. Recent evidence suggests that there are
      four major factors that are the most important in the initiation and maintenance
      of ARF. These include a decrease of glomerular capillary permeability, back-leak
      of glomerular filtrate, tubular obstruction, and intrarenal vasoconstriction.
      Both sub-lethal and lethal cell injury have been found in ARF, with the latter
      related either to necrosis or apoptosis. Intrarenal vasoconstriction, related to
      a shift in the balance between endothelin and endothelium-derived nitric oxide,
      is receiving considerable attention as a major contributor to the pathogenesis of
      ARF, with therapeutic maneuvers targeted at restoring the usual balance, and
      relieving intrarenal vasoconstriction. If such approaches prove to be of value,
      the outcome of patients with this serious condition might be substantially
      improved.

PMID- 9573568
TI  - Role of growth factors in acute renal failure.
AB  - Recovery from ischemic and nephrotoxic acute renal failure (ARF) requires the
      replacement of damaged tubular cells with new ones that restore the continuity of
      the renal epithelium. The repair process involves a number of growth factors
      produced in renal tissue that participate as autocrine or paracrine regulators in
      the repair process. The aim of this review is threefold: (1) to focus on the role
      of local growth factors such as EGF, TGF-alpha, IGF-1, HGF and TGF-beta in renal
      regeneration immediately after an acute renal insult. Receptors for these growth
      factors have been found in renal epithelial cells, medullary interstitial cells
      and glomeruli. These mediators play an important role in renal repair by
      promoting tubular cell proliferation. (2) A review the data supporting the
      administration of these growth factors in animal models of ARF, and the
      possibility of using these mediators in humans for the purpose of accelerating
      renal recovery and decreasing the morbidity and mortality rates, and the costs of
      multidisciplinary medical care, is presented. (3) Finally, the possibilities of
      introducing supportive therapy aimed at specific targets such as RGD peptides to
      reduce intratubular obstruction, atrial natriuretic factor to improve altered
      glomerular hemodynamics, and cell therapy such as bioartificial renal tubule in
      association with dialysis are discussed.

PMID- 9573569
TI  - Acute renal failure as a part of multiple organ failure: the slippery slope of
      critical illness.

PMID- 9573570
TI  - Pathogenesis of renal failure in sepsis.

PMID- 9573571
TI  - Role of soluble mediators in sepsis and renal failure.

PMID- 9573572
TI  - Transfer of endogenous pyrogens across artificial membranes?
AB  - Synthetic high-flux dialyzer membranes used in continuous veno-venous
      hemofiltration are permeable to middle molecular size endogenous pyrogens, the
      pro-inflammatory cytokines IL-1 beta and TNF-alpha. The quantities removed by
      sieving are, however, negligible in vitro as well as in vivo. Adsorption of
      cytokines to the membrane polymer is the major mechanism of pyrogen removal.
      Adsorption seems to be semispecific for pro-inflammatory cytokines because levels
      of anti-inflammatory mediators were not changed or even increased during CVVH.
      Thus, CVVH may change cytokine profiles in septic patients supporting the
      predominance of anti-inflammatory over pro-inflammatory activity in plasma. It
      remains to be demonstrated whether modifications of extracorporeal blood
      purification systems (high-volume CVVH, plasma separation + adsorption) are able
      to amplify the change in cytokine profiles and whether this change influences
      outcome of septic patients.

PMID- 9573573
TI  - Hepatorenal syndrome: definition, pathophysiology, clinical features and
      management.

PMID- 9573575
TI  - The kidney in heart failure.

PMID- 9573574
TI  - The hemolytic uremic syndrome.

PMID- 9573576
TI  - Stress metabolism and nutritional support in acute renal failure.

PMID- 9573577
TI  - Use of diuretics in the acute care setting.
AB  - The use of diuretics in the acute care setting (intensive care units, operating
      rooms and emergency departments) is an area of significant clinical and
      laboratory research. These agents are frequently used to facilitate fluid
      management and in the hopes of protecting the kidneys from injury. The pros and
      cons of continuous infusion of loop diuretics, and albumin supplementation are
      discussed along with the issues related to their use to avoid dialysis or to
      improve outcome. In addition, the evidences is support of the use diuretics to
      prevent or treat acute failure in the acute care setting are reviewed and
      discussed.

PMID- 9573578
TI  - Hemodynamic support and the role of dopamine.
AB  - The armamentarium of the critical care nephrologist contains several vasoactive
      and inotropic drugs with powerful effects on the systemic circulation. The
      physiologically logical use of these drug can be life-saving and have important
      beneficial effects on renal function. Such drug use must absolutely not be based
      on a "fixed dosage," but must instead be goal-directed with the aim of achieving
      those physiological states associated with hemodynamic stability and adequate
      vital organ perfusion. The achievement and maintenance of these goals must be
      prompt and guided by appropriate invasive hemodynamic monitoring and may require
      frequent changes in dosage. When these measures are adhered to, renal protection
      and clinical success are a much more likely outcome than when stereotyped
      approaches are followed.

PMID- 9573579
TI  - Plasma dopamine concentration and effects of low dopamine doses on urinary output
      after major vascular surgery.
AB  - To evaluate plasma dopamine concentration and the effects of low doses infusion
      on urinary output after abdominal vascular surgery in patients with renal
      function impairment we performed a prospective clinical study. Twenty
      hemodynamically stable patients (mean age 66.6 years), with serum creatinine
      concentration < 2 mg %, who undergoing general anesthesia for major vascular
      surgery participated. A low dose of dopamine (3 micrograms/kg/min) was
      administrated to patients with postoperative protracted urinary output < 0.5
      ml/kg/hr for at least eight hours. Plasmatic determinations were taken at T0 (no
      dopamine administration), when urinary output began to increase, or if not, after
      two hours (T1), at eight (T2), and 24 (T3) hours after the beginning of infusion.
      After 24 hours the dopamine infusion was stopped and the patient's plasmatic
      level was measured four hours later (T4). Dopamine plasma concentrations were
      measured using high-performance liquid chromatography. Plasma dopamine
      concentration increased in all patients and reached a steady state at T2 (T2 =
      76.41 +/- 16.84 ng/ml). Dopamine induced a concentration-dependent increase in
      urinary output (T0 = 0.45 +/- 0.14; T1 = 1.49 +/- 1.11; T2 = 2.34 +/- 1.44; T3 =
      1.57 +/- 0.57; T4 = 0.85 +/- 0.7 ml/kg/hr). Three patients did not have an
      enhanced urinary output after dopamine infusion; they did have a prolonged
      clamping time and operation time (162 +/- 24 and 570 +/ 30 min, respectively). We
      conclude that low dose dopamine induces a dose-dependent increase of urinary
      output. This phenomenon also has been found in patients when their plasma
      concentration had not yet reached the steady-state. Lack of responsiveness to
      dopamine suggests a renal function impairment probably due to the prolonged
      aortic clamping time.

PMID- 9573580
TI  - Metabolic acidosis in the critically ill: lessons from physical chemistry.
AB  - There is growing interest in quantitative physical chemical analysis of acid-base
      physiology among intensivists. Acid-base dilemmas seen in the intensive care unit
      are not always well addressed by the traditional approaches. Quantitative
      physical chemical analysis also allows for the exploration of unexplained anion
      induced acidosis where the familiar anion gap is insufficient or inaccurate. This
      approach emphasizes the application of accepted physical chemical principles and
      identification of independent and dependent acid-base variables. In aqueous
      solutions, water dissociation is the major source of free hydrogen ions.

PMID- 9573581
TI  - Antibiotic therapy and microbiologic considerations in the intensive care unit.

PMID- 9573582
TI  - Role of renal biopsy in the diagnosis and prognosis of acute renal failure.

PMID- 9573583
TI  - Coagulation disorders in acute renal failure.

PMID- 9573584
TI  - Imaging techniques in acute renal failure.

PMID- 9573586
TI  - The place of intermittent hemodialysis in the treatment of acute renal failure in
      the ICU patient.

PMID- 9573585
TI  - Indications and criteria for initiating renal replacement therapy in the
      intensive care unit.
AB  - The decision to initiate renal replacement therapy is usually based on a careful
      assessment of conflicting priorities in the care of critically ill patients. It
      is particularly difficult because of the lack of information on what are the
      optimal criteria and indications for the application of renal replacement therapy
      (RRT) in the intensive care unit (ICU). As we will discuss in this paper, even
      though there are several time-honored indications for initiating dialytic therapy
      in patients with near end-stage renal failure, such indications may not apply to
      the management of acute renal failure (ARF). In fact, there are several reasons
      why a more aggressive approach and an earlier intervention may be justified in
      the ICU.

PMID- 9573587
TI  - History and development of continuous renal replacement techniques.
AB  - In 1966 two research groups, one in the United States and the other in Germany,
      were independently evaluating new membranes for renal replacement techniques.
      These filters were characterized by high filtration rates, where solutes up to a
      certain molecular weight were filtered by convection. At the same time the
      understanding of the transport mechanisms through membranes was improving. In
      1976 Burton created the term "hemofiltration" for this new convective technique,
      and the first multicenter trial was initiated to evaluate its effectiveness for
      treating chronic renal failure. In 1977 Kramer in Gottingen (Germany) developed
      the continuous arteriovenous hemofiltration (CAVH) technique, which used a
      systemic arteriovenous pressure difference in an extracorporeal circuit to
      continuously produce an ultrafiltrate. The advantages of this effective method
      for elimination of fluid and solutes were its technical simplicity and the
      hemodynamic stability of even critically ill patients. Therefore, it soon became
      a widely used method for treating acute renal failure in intensive care patients.
      However, its limited capacity to remove nephrotoxins in the presence of high
      catabolism and complications connected to the arterial access lead to the
      development of a venovenous pump-driven technique (CVVH) in order to become
      independent from the systemic circulation and the arterial access. Further
      progress to improve solute clearance was made by combining the convective
      principle of hemofiltration with the diffusive transport of dialysis (continuous
      arteriovenous hemodialysis or hemodiafiltration). Today this combination has
      become the most effective renal replacement technique for treating acute renal
      failure in critically ill patients.

PMID- 9573588
TI  - Continuous versus intermittent renal replacement therapy in the intensive care
      unit.

PMID- 9573589
TI  - Classical and alternative indications for continuous renal replacement therapy.

PMID- 9573590
TI  - Renal replacement therapy in acute renal failure: solute removal mechanisms and
      dose quantification.
AB  - Based on numerous studies demonstrating a direct relationship between survival
      and delivered hemodialysis (HD) dose in end-stage renal disease (ESRD),
      quantification of delivered HD is now routinely performed in this setting.
      Recently, investigators have also begun applying kinetic modeling principles to
      quantify delivered dialysis dose in patients with acute renal failure (ARF). One
      purpose of this article is to review these ARF studies. However, a broader
      objective is to provide an overview of the solute removal capabilities of both
      intermittent and continuous therapies used in ARF. To achieve this goal, the
      dialytic removal mechanisms for solutes over a wide molecular weight spectrum are
      discussed.

PMID- 9573591
TI  - Outcome studies of continuous renal replacement therapy in the intensive care
      unit.

PMID- 9573592
TI  - Temporary vascular access for extracorporeal renal replacement therapies in acute
      renal failure patients.
AB  - Temporary vascular access is an essential component to perform any extracorporeal
      renal replacement therapy (RRT) in the acute renal failure patient. RRT used in
      the acute setting may be categorized in two groups: intermittent (IRRT) and
      continuous (CRRT). Therapeutic indications are based on clinical and technical
      considerations. Continuous modalities are mainly utilized in intensive care units
      for hemodynamically compromised patient. Initially performed spontaneously via an
      arteriovenous circuit, CRRT modalities have progressively become venovenous with
      the circulatory assistance of a blood pump. Since both intermittent and
      continuous RRT modalities are now performed almost exclusively by venovenous
      modalities, this article deals exclusively with temporary venous catheters. At
      present, double-lumen catheters represent the most common vascular access for RRT
      modalities. Semi-rigid polyurethane catheters currently used in case of emergency
      are limited to short term use. Hemocompatible, flexible silicone catheters, less
      aggressive for the vessels, seem better suited for the medium and long term run.
      The tunneled silicone catheters (DualCath type) meet the short and long term
      needs, and allow for blood flow rates up to 400 ml/min. The internal jugular
      vein, particularly the right one, seems to warrant the proper functioning of
      catheters while reducing the risk of stenotic complications. Subclavian access
      should be limited in time and reserved for silicone catheters in order to limit
      the risk of stenosis and/or thrombosis. Femoral access, very useful in cases of
      emergency and respiratory problems, greatly impairs the patient's mobility and
      should be limited by time to prevent thrombosis and/or infection. Late and/or
      delayed dysfunctioning of catheters are indicative of a thrombosis. Performance
      standards of catheters are less of a limiting factor in continuous low flow RRT
      modalities than in the intermittent ones. Finally, careful handling of the
      catheter essential to prevent infectious complications.

PMID- 9573593
TI  - Electrolyte disorders and substitution fluid in continuous renal replacement
      therapy.
AB  - Electrolyte balances during acute renal failure treated with continuous
      convective techniques, such as continuous arteriovenous hemofiltration (CAVH) and
      its pumped variants, are largely dependent on the eloctrolyte plasma
      concentration available for ultrafiltration, the ultrafiltration rate and the
      composition of the replacement solution. As blood sodium concentrations measured
      by potentiometry (Na +P) and the total ultrafiltrate sodium concentration are
      very similar, Na +P can be taken as the value of ultrafilterable sodium when
      choosing the correct sodium concentration in the substitution fluid. In CAVH, the
      ultrafiltrate contains about 3 m Eq/liter of calcium and 1 m Eq/liter of
      magnesium that must be replaced by the substitution fluid in order to prevent
      hypocalcemia and hypomagnesemia. In addition, if plasma potassium levels are
      normal, 3 to 4 mEq/liter of potassium should be added to the replacement fluid to
      avoid hypokalemia. Although convection and diffusion are combined in continuous
      hemodialysis, solute transport is largely mediated by convection; however, the
      net removal of sodium and calcium is significantly influenced by their
      concentrations in the dialysate, and the risk of hypomagnesemia and hypokalemia
      can be attenuated by adjusting magnesium and potassium concentrations in the
      dialysis solution to levels near to the plasma water values. Since critically ill
      patients are prone to developing dialysis-induced hypophosphatemia, phosphorous
      must be monitored and supplemented if necessary, Since CRRT works continuously,
      serious derangement in fluid and electrolyte homeostasis may occur in the absence
      of careful prescription and extremely vigilant monitoring.

PMID- 9573594
TI  - Acid-base balance and replacement solutions in continuous renal replacement
      therapies.

PMID- 9573595
TI  - Continuous renal replacement therapy: evolution in technology and current
      nomenclature.
AB  - The evolution of technology and biomaterials has permitted a parallel development
      of renal replacement therapies in the acute, critically ill patient. From the
      original description of continuous arteriovenous hemofiltration (CAVH), new
      techniques such as continuous venous venous hemofiltration (CVVH),
      hemodiafiltration (HDF) and high flux dialysis (HFD) have been developed and
      clinically utilized. A parallel improvement in efficiency has been achieved with
      daily clearances of urea as high as 50 liters or more. The use of special highly
      permeable dialyzers has also permitted increases in the clearances of larger
      solutes, thus leading to significant removals of chemical substances involved the
      acute inflammation and sepsis. In this field, recent observations have suggested
      the use of hemofiltration with high volumes of fluid exchange. The hardware and
      software of the newer continuous renal replacement therapy (CRRT) systems are
      certainly the key points in achieving these results and in safely performing such
      challenging techniques.

PMID- 9573596
TI  - Drug dosing adjustments during continuous renal replacement therapies.

PMID- 9573597
TI  - Continuous renal replacement therapy in critically ill patients.
AB  - We describe our experience with continuous renal replacement therapy (CRRT) in
      critically ill neonates. From June 1995 to June 1997 36 critically ill oliguric
      or anuric infants and children underwent continuous arterio-venous (N = 17) or
      veno-venous (N = 15) renal support. In addition, four neonates were treated with
      continuous ultrafiltration (CUF) during extracorporeal membrane oxygenation
      (ECMO) because of severe diuretic-resistant hypervolemia. Their mean age was 9.8
      +/- 1.5 days, their mean body weight 3.0 +/- 0.1 kg. The membrane surface area of
      the hemofilters ranged from 0.015 m2 to 0.2 m2 and the priming volume from 3.7 to
      15 ml. For pump-driven hemofiltration a roller pump with pressure alarms, an air
      trap, an air bubble detector, and small blood lines was used. Fluid balance was
      controlled by a microprocessor controlled unit. The ultrafiltrate substitution
      fluid was based on bicarbonate in the majority of the patients and was partially
      or totally replaced according to the clinical situation. The mean duration of
      renal support was 97 +/- 20 hours, ranging from 14 to 720 hours. During arterio
      venous and veno-venous hemofiltration the mean blood flow rates were 7.0 +/- 1.2
      ml/min and 23.1 +/- 2.4 ml/min (P < 0.01), respectively, and the mean
      ultrafiltration rates 3.3 +/- 0.4 and 9.5 +/- 1.9 ml/min/m2 (P < 0.01),
      respectively. During continuous hemodiafiltration urea clearances increased by
      300%. Overall survival rate was 66%. CRRT related complications included local
      bleeding at the catheter entrance site, partial thrombosis of the inferior or
      superior caval veins and transient ischemia due to femoral artery catheters.
      Continuous hemofiltration either driven in the arterio-venous or veno-venous mode
      is a very effective method of renal support for critically ill neonates to
      control fluid balance and metabolic derangement. Urea clearance can be improved
      by adding some dialysate fluid in a countercurrent direction to blood flow.

PMID- 9573598
TI  - Hemofiltration during cardiopulmonary bypass.
AB  - Several factors combine to facilitate the evolution towards heart and multi-organ
      failure following cardiac surgery. Some of these factors are related to pure
      cardiac aspects, for example, the existence of a preoperative heart disease, the
      use of aortic cross clamping or performance of cardiotomy. Cardiopulmonary bypass
      (CPB) also plays an important role in the occurrence of postoperative organ
      dysfunctions by two principal means. It induces a profound hemodilution, which
      impairs oxygen transport through tissues. This phenomenon becomes obvious in the
      postoperative period by the existence of increased transpulmonary O2 gradients,
      extravascular lung water volume and subsequent impairments of O2 transport. (2)
      Cardiopulmonary bypass is deleterious by triggering an important inflammatory
      reaction. This reaction is largely related to the ratio of the circuit area to
      the patient's body surface area and is therefore maximal in children. It has been
      widely demonstrated that the very early paths of this reaction imply several
      humoral factors including kinins, coagulation factor XII and complement
      fragments. The activation of these factors is self-amplified and triggers both
      expression and release of numerous mediators by endothelial cells and leukocytes.
      Finally, these mediators are responsible for the well described "post-bypass
      syndrome," which is, from a clinical viewpoint, very close to hyperkinetic septic
      shock. Several methods have been proposed to reduce the deleterious effects of
      both cardiac surgery and CPB. The older one is hypothermia that considerably
      reduces the triggering of the inflammatory mediator network. Heparin-coated
      circuits may also reduce this reaction to some extent. Hemofiltration has been
      introduced in the 1990s in CPB management. Because of its very high tolerance in
      patients with compromised circulatory status this technique was already used in
      the postoperative period to treat patients with acute renal failure. Initially
      hemofiltration was intended to correct the accumulation of extravascular water
      during or immediately following the surgical procedure. Nevertheless, several of
      its side-effects appeared to be useful, such as the reduction of postoperative
      blood loss and immediate improvement in hemodynamics. Several studies attempted
      to point out the mechanism of action of hemofiltration and although removal of
      inflammatory mediator occurs, there is currently no proof that this removal is
      the actual mechanism by which this technique acts.

PMID- 9573599
TI  - Plasmapheresis in the critically ill patient.
AB  - Despite the wide number of diseases currently or previously treated with plasma
      exchange and plasmapheresis, the clinical effectiveness of these treatments has
      been established by large, controlled clinical trials only in few clinical
      conditions. The firmly accepted and the possible indications for these techniques
      in critically ill patients are reviewed and discussed, as well as their
      complications and possible side effects.

PMID- 9573600
TI  - Preliminary experience with high-volume hemofiltration in human septic shock.

PMID- 9573601
TI  - Continuous plasma filtration coupled with sorbents.
AB  - An in vitro system composed of a plasma separation membrane coupled with natural
      (charcoal) or synthetic (Amberlite, Amberchrome) types of sorbents was evaluated
      for the simultaneous removal of proinflammatory cytokines (TNF-alpha, IL-1 beta
      and IL-8) and cytokine antagonists [interleukin (IL)-1 receptor antagonist (IL
      1Ra), soluble tumor necrosis factor-alpha (TNF-alpha) receptor I and II (sTNFR I
      and II)] in whole blood spiked with bacterial lipopolysaccharide (LPS). These
      studies showed that plasma filtration rather than ultrafiltration significantly
      increased the clearance of all cytokines, particularly TNF-alpha, and the
      synthetic (Amberlite-type of resin) but not natural (uncoated charcoal) membrane
      could extensively absorb almost 100% of plasma filtered IL-Ra, IL-1 beta and IL
      8, but only 40% of TNF-alpha. Other synthetic (Amberchrome) membranes could also
      effectively (80%) remove TNF-alpha. In the complex scenario of sepsis, the
      simultaneous removal of excess proinflammatory and/or immunomodulatory mediators
      may play a role in reducing the hemodynamic alterations, thus resulting in
      enhanced patient survival. Whether this occurs in the human setting awaits the
      results of an ongoing clinical investigation.

PMID- 9573602
TI  - Quo vadis CRRT?

PMID- 9573603
TI  - Cupins: a new superfamily of functionally diverse proteins that include germins
      and plant storage proteins.

PMID- 9573604
TI  - Genetically modified livestock for the production of human proteins in milk.

PMID- 9573605
TI  - Genotypic methods for diagnosis of mycoplasmal infections in humans, animals,
      plants and cell cultures.

PMID- 9573606
TI  - Uses of plant gene silencing.

PMID- 9573607
TI  - Antisense therapeutics.

PMID- 9573608
TI  - Foreign peptides expressed in engineered chimeric self molecules.

PMID- 9573611
TI  - Cell wall proteins of Saccharomyces cerevisiae.

PMID- 9573612
TI  - Interrelationships between protein surface adsorption and bacterial adhesion.

PMID- 9573613
TI  - Diphenol oxidases, enzyme-catalysed browning and plant disease resistance.

PMID- 9573614
TI  - Investigating the performance of intensive mammalian cell bioreactor systems
      using magnetic resonance imaging and spectroscopy.

PMID- 9573615
TI  - Chromatin structure in bands and interbands of polytene chromosomes imaged by
      atomic force microscopy.
AB  - Polytene chromosomes from Drosophila melanogaster, observed from squash
      preparations, and chromosomes from Chironomus thummi thummi, investigated under
      physiological conditions, are imaged using an Atomic Force Microscope. Various
      chromatin fiber structures can be observed with high detail in fixed chromosomes
      and correspond to structures which are also observed in chromosomes of diploid
      cells. Unfixed chromosomes can be imaged in buffer and show less fiber-like
      details because of the inherent soft nature of the chromatin material.

PMID- 9573616
TI  - Three-dimensional reconstruction of metal replicas of the Helicobacter pylori
      vacuolating cytotoxin.
AB  - The Helicobacter pylori vacuolating cytotoxin (VacA) forms high molecular weight
      homooligomers which contain either six or seven copies of a 95-kDa polypeptide.
      Electron microscope visualization of carbon platinum replicas of quick-freeze,
      deepetched, preparations of VacA has revealed that the oligomers are arranged in
      flower-like structures with six- or sevenfold radial symmetry, depending on the
      number of 95-kDa oligomers that they contain. Each monomer is structured in two
      subunits of 37 and 58 kDa connected by an exposed loop which is a site for
      proteolytic cleavage. In preparations of VacA which had undergone extensive
      cleavage at the exposed loop, oligomers of both six- and seven-fold symmetry
      which appeared flatter were observed; these latter were interpreted as molecules
      which had lost a complete set of one of the subunits. We exploited a 3D
      reconstruction of metal replicas of quick-freeze, deep-etched, oligomers,
      representing the four types of molecules described. All the molecules appear to
      adhere with the same face toward the mica. Images of rotary shadowed oligomers
      were processed by multivariate statistical analysis to evidence clusters of
      equivalent and homogeneous oligomers. 3D reconstructions of the replicas so
      classified were performed by random conical tilt tomography. In the case of
      intact molecules (not cleaved) the reconstructions represent both the outer and
      the inner surfaces of the mold; the latter gives a reasonably accurate sense of
      the upper surface of the VacA oligomers. These data support the hypothesis that
      VacA is an AB type toxin and suggest a model in which the smaller of the two
      subunits is arranged in a uniform ring on the surface of the molecule in such a
      way as to contribute to the overall stability of the molecule.

PMID- 9573617
TI  - 26S proteasome structure revealed by three-dimensional electron microscopy.
AB  - In 26S proteasomes, "19S cap complexes" associate with either one or both ends of
      the barrel-shaped 20S core complex. These regulatory complexes which comprise
      about 20 different subunits, including 6 ATPases of the AAA family, are thought
      to recognize ubiquitinated substrate proteins, to dissociate and unfold them
      before threading them into the 20S core where they are degraded. Here, we examine
      the structure of 26S proteasomes from Drosophila embryos and Xenopus oocytes by
      electron microscopy. Image analysis reveals a rather flexible linkage between the
      19S caps and the 20S core, with a peculiar wagging-type movement of the caps
      relative to the core. At this stage of the analysis, it is not clear whether this
      movement is relevant in terms of function. Three-dimensional reconstructions,
      taking this into account, provide first insights into the remarkably complex
      structure of the 19S caps and allows us to put forward a composite model of the
      entire 26S complex.

PMID- 9573618
TI  - Structural changes of the Escherichia coli GroEL-GroES chaperonins upon complex
      formation in solution: a neutron small angle scattering study.
AB  - We applied neutron scattering in conjunction with deuterium (D-) labeling in
      order to obtain information about the domain structure of GroEL and GroES
      isolated and in the complex. Each subunit of the heptameric GroES consists of two
      domains, a core domain (Met1 to Lys15 and Lys34 to Ala97) and an intervening loop
      region (Glu16 to Ala33). Neutron scattering shows that both regions change their
      conformation upon GroEL/GroES complex formation. The interdomain angle between
      the core regions of the heptameric GroES increases from 120 to 140 degrees,
      leading to a less dome-like shape of GroES, and the loop regions turn inwards by
      75 degrees. The 23 C-terminal amino acids of the 14 GroEL subunits (Lys526 to
      Met548), which are unresolved in the crystal structure, are located either at the
      bottom of the cavity formed by the seven-membered GroEL ring or at the inner wall
      of the cavity. Upon complex formation the apical domains of GroEL move outwards,
      which facilitates binding of GroES at a Gro-EL-GroES center-to-center distance of
      (87 +/- 8) A. These structural changes may be important for the dissociation of
      the unfolded protein bound to the central cavity upon GroES binding. The overall
      structure determined by neutron scattering in solution tallies with the
      crystallographic model published after completion of this study. Differences in
      the conformation of GroES observed in the complex by the two methods support the
      view that the chaperonin complex is a flexible molecule which might switch in
      solution between different conformations.

PMID- 9573619
TI  - Three-dimensional structure of HIV-1 Rev protein filaments.
AB  - The HIV-1 Rev protein facilitates the export of incompletely spliced and
      unspliced viral mRNAs from the nucleus. Rev polymerizes into two types of
      filaments in vitro. In the presence of RNA, Rev forms poorly ordered structures,
      while in the absence of RNA it polymerizes into regular hollow filaments. We have
      determined the helical structure of the latter filaments by analysis of cryo
      electron micrographs, taking into account STEM measurements of mass-per-unit
      length. They are made up of Rev dimers, arranged in a six-start helix, with 31
      dimers in 2 turns, a pitch angle of 45 degrees, and an interstrand spacing of 3.8
      nm. Three-dimensional reconstruction at 2.1 nm resolution reveals a smooth outer
      surface and a featured inner surface, with outer and inner diameters of
      approximately 14.8 and approximately 10.4 nm, respectively. The Rev dimer has a
      "top-hat" shape with a cylinder approximately 3.2 nm in diameter and
      approximately 2.2 nm high, pointing inward: the thinner rim areas pack together
      to form the filament wall. Raman spectroscopy shows polymerized Rev to have
      approximately 54% alpha-helix and 20-24% beta-sheet content. Electron
      microdiffraction of aligned filaments reveals a broad meridional reflection at
      approximately (0.51 nm(-1, suggesting approximate alignment of the alpha-helices
      with the filament axis. Based on these data, a molecular model for the Rev
      filament is proposed.

PMID- 9573620
TI  - Evidence for local 32 symmetry in homotrimeric riboflavin synthase of Escherichia
      coli.
AB  - Riboflavin synthase is a trimer of identical 23-kDa subunits. The primary
      structure is characterized by considerable similarity of the C-terminal and N
      terminal parts. Recombinant riboflavin synthase of Escherichia coli and Bacillus
      subtilis was crystallized by the vapor diffusion method. Crystals of E. coli
      riboflavin synthase belong to the orthorhombic system, space group P2(1)2(1)2(1),
      with unit cell dimensions a = 53.2 A, b = 117.6 A, c = 150.9 A, alpha = beta =
      gamma = 90 degrees. They diffract to better than 3.3 A resolution and have
      presumably one trimer in the asymmetric unit. The self rotation function
      indicates local 32 symmetry. Twofold local symmetry is an unexpected result in a
      trimeric protein. In conjunction with primary structure arguments and mechanistic
      considerations, we propose that the protein is a pseudohexamer where each of the
      peptide subunits fold into two topologically similar domains.

PMID- 9573621
TI  - Two-dimensional crystals of protein kinase C.
AB  - Three two-dimensional (2D) crystal forms of protein kinase C (PKC) alpha and
      three of PKC delta have been grown on lipid monolayers composed of
      dioleoylphosphatidylcholine: dioleoylphosphatidylserine: (45:50:5 molar ratio).
      In the absence of DO, two additional 2D crystals of PKC delta are seen,
      suggesting that the presence of diolein (DO) alters the conformation of intact
      PKC at the lipid surface. Reconstructions of electron micrographs of these eight
      lattices show good reproducibility and indicate that several are appropriate for
      three-dimensional reconstruction to 20 A resolution.

PMID- 9573622
TI  - High-resolution crystals of methionine aminopeptidase from Pyrococcus furiosus
      obtained by water-mediated transformation.
AB  - The monoclinic crystal form of methionine amino-peptidase from Pyrococcus
      furiosus (MAP-Pfu) has been crystallized from four different conditions. Native
      crystals belong to space group P2(1) with typical unit-cell dimensions a = 53.4,
      b = 85.1, c = 72.7 A, beta = 107.7 degrees and diffract to 2.9-4.5 A resolution.
      However, there is a problem of nonisomorphism among the crystals. Water-mediated
      transformation to low-humidity form occurs by reduction of the relative humidity
      of crystal environment to 79%. The unit-cell dimensions of transformed crystals
      are a = 51.9, b = 83.3, c = 70.3 A, beta = 105.9 degrees, and the calculated
      solvent content is 3.9% less than in original crystals. Transformation to low
      humidity form is accompanied by 1.7 times reduction of overall temperature
      factors, extension of diffraction resolution up to 1.75 A, without change or
      reduction of crystal mosaicity, and improvement in stability to X-ray radiation.
      The water-mediated transformation also appears to relieve the problem of
      nonisomorphism among the original MAP-Pfu crystals.

PMID- 9573623
TI  - Crystallization and preliminary X-ray analysis of Streptococcus pneumoniae
      hyaluronate lyase.
AB  - A fully active 83-kDa truncated form of recombinant hyaluronate lyase from
      Streptococcus pneumoniae was crystallized by the hanging drop vapor diffusion
      method using ammonium sulfate as a precipitating agent. Crystals grew at room
      temperature using a variety of buffers with pH around 6. The crystals diffract X
      rays beyond 2.0 A resolution using Cu K alpha radiation and a rotating-anode X
      ray source. They belong to the orthorhombic space group P2(1)2(1)2(1) with unit
      cell dimensions, a = 84.2, b = 104.2, c = 104.6 A, and alpha = beta = gamma =
      90.0 degrees. The VM value of 2.9 A3/Da is consistent with only one molecule of
      the enzyme in the asymmetric unit and the solvent content of 57%. Diffraction
      data 94.7% complete to 2.0 A resolution with Rsym of 5.4% were collected from one
      native crystal at room temperature. The search for heavy-atom derivatives to
      solve the structure is in progress.

PMID- 9573625
TI  - Modelling the chemical speciation of trace metals in the surface waters of the
      Humber system
AB  - Calculations have been performed to estimate the chemical speciation at
      equilibrium of six divalent trace metals (Co, Ni, Cu, Zn, Cd, Pb) in riverine,
      estuarine and marine surface waters of the Humber system. The Windermere Humic
      Aqueous Model (WHAM) was used to compute distributions of dissolved metals. In
      the rivers, the free aquo ion (M2+) is a major part of dissolved Co, Ni, Zn and
      Cd, but accounts for less than 1% of Cu and Pb. The main complexes are formed
      with carbonate ligands and dissolved natural organic matter, represented by
      fulvic acid. In the low-salinity region of the estuary and in seawater,
      complexation with fulvic acid is less significant, although most of the Cu is
      still in this form, while the speciation of Cd is dominated by chloride
      complexes. Adsorption of metals by suspended particulate matter was calculated
      with a simple model involving the concentrations of the free aquo ions (M2+) and
      H+, together with a constant for each metal estimated from laboratory adsorption
      data. Calculated adsorbed concentrations were used to predict the partition
      coefficient (KD) for each metal under different circumstances. The values can
      vary by an order of magnitude or more, depending upon solution conditions.
      Typical values for rivers, low-salinity water and seawater are within one order
      of magnitude of observations. However, there is a general tendency to
      underestimate KD, possible reasons being (1) neglect of electrostatic enhancement
      of adsorption at low ionic strengths; and (2) analytical overestimation of
      particulate metal in equilibrium with the solution phase. There is a strong case
      for the development of a more sophisticated adsorption model.

PMID- 9573624
TI  - Purification, crystallization, and preliminary X-ray crystallographic data
      analysis of small heat shock protein homolog from Methanococcus jannaschii, a
      hyperthermophile.
AB  - A gene coding for a small heat shock protein homolog from the hyperthermophilic
      methanogenic Archaeon Methanococcus jannaschii was cloned. This gene was
      overexpressed in Escherichia coli harboring rare codon tRNAs and its protein
      purified and crystallized. Crystals displayed the space group R3 with unit cell
      dimensions a = b = 171.46 A and c = 102.13 A in a hexagonal axis setting. These
      crystals grew in one week and diffracted to 3.2 A resolution. The presence of
      eight molecules in the asymmetric unit gives a Vm value of 2.2 A3/Da and a
      solvent content of 44% by volume. The 24-molecule complex is generated from a
      subunit by a combination of crystallographic threefold symmetry and three types
      of noncrystallographic symmetries (a two-, a three-, and a fourfold).

PMID- 9573626
TI  - Release of heavy metals from European and Asian porcelain dinnerware.
AB  - Samples of porcelain dinnerware manufactured in five European and three Asian
      countries before the mid-1970s and subsequently brought into the US were
      subjected to acid leaching tests to investigate the release of heavy metals.
      Forty-six dishes decorated with decals or hand painted designs applied over the
      glaze were examined. Included in the selection were dishes from major
      manufacturers of fine dinnerware (Haviland Limoges, Rosenthal, Noritake) as well
      as samples from lesser-known or unidentified factories. During 24-h tests with 4%
      acetic acid, half of the samples (23 dishes) released lead in concentrations
      exceeding the US Food and Drug Administration (FDA) allowable maximum of 3.0
      micrograms/ml and another 17 dishes released lead in concentrations ranging from
      0.1 to 2.9 micrograms/ml. Five dishes released cadmium, but only one value
      exceeded the FDA limit of 0.5 microgram/ml. Zinc, cobalt, copper and chromium
      were also released by some of the dishes. None of the acetic acid solutions
      contained measurable concentrations of nickel although this metal, as well as
      those named above, could be extracted from some samples with 6 M nitric acid. The
      FDA has not established dinnerware extraction limits for any metals except lead
      and cadmium. All overglaze-decorated dishes imported into the US before the mid
      1970s should be tested for lead release before they are used in the preparation,
      serving, or storage of food.

PMID- 9573627
TI  - Behavior of 60Co and 134Cs in a Canadian Shield lake over 5 years.
AB  - Radionuclides were added to the anoxic hypolimnion of a Canadian Shield lake to
      simulate the nuclear fuel waste disposal scenario where radionuclides might enter
      the bottom waters of a lake. The radionuclides remained in the hypolimnion until
      lake mixing at autumn turnover after which 60Co was rapidly lost and 134Cs was
      slowly lost from the water. Only 0.4% of the 60Co and 0.6% of the 134Cs remained
      in the water at year 5. Highest concentrations occurred in periphyton and filter
      feeders, Holopedium gibberum and clams (Anodonata grandis grandis). From maximum
      annual concentrations in clam tissues, it was estimated that the availability of
      60Co for uptake had a half-time (t1/2) of 835 days in the lake, whereas that for
      134Cs was 780 days. Loss rate coefficients, k, for the radionuclides from taxa
      ranged from 0.0008 to 0.0043 day-1 (t1/2 = 161-866 days) for 60Co and from 0.0009
      to 0.005 day-1 (t1/2 = 139-770 days) for 134Cs. Cobalt-60 concentrations in
      forage fish were low, whereas 134Cs concentrations increased over the first year
      or two, then slowly declined. On the basis of k values measured for forage fish,
      the biological half-time of 134Cs in forage fish ranged from 428 to 630 days.
      Maximum 134Cs concentrations in forage fish were higher following hypolimnetic
      addition than epilimnetic addition. Relatively high 134Cs concentrations in
      periphyton at year 5 point to the importance of benthic pathways in the recycling
      of contaminants to higher trophic levels. The presence of 134Cs in biota 5 years
      after the addition, long after concentrations were no longer detectable in
      surface waters, is evidence of the persistence of Cs in aquatic systems. The k
      values (or t1/2 values) for the loss of 60Co and 134Cs from water and their
      uptake and loss from biota can be used to establish parameter values for
      assessment models. The results demonstrate that assessment models should account
      for the release of radionuclides from sediment and their subsequent recycling in
      the food chain when modeling over the long term after the end of a radionuclide
      release to the environment.

PMID- 9573628
TI  - Field evaluation of a mathematical model of PCB transfer through the freshwater
      aquatic food chain.
AB  - A mathematical model of the transfer of PCBs through the freshwater aquatic food
      chain is described. The model predicts concentrations of 11 selected individual
      PCB congeners in forage fish and pike, from source terms of atmospheric
      deposition and watershed soil concentrations. Model performance has been
      evaluated using data from a field study conducted in a section of the River
      Severn near Birmingham, UK. Results demonstrate that with the exception of
      congener 52, overall model predictions of individual PCB concentrations in both
      forage fish and pike underestimate measured concentrations by factors of between
      approximately 3 and 25 for individual congeners. Closer examination suggests that
      whilst model equations contribute to these underestimations, a significant factor
      is the lack of knowledge of additional PCB inputs to the waterbody.

PMID- 9573629
TI  - The contamination of birds with organic pollutants in the Lake Baikal region.
AB  - Lake Baikal is considered to be the largest reservoir of fresh natural water in
      the world. Nevertheless industrial enterprises on its banks as well as river
      effluents contaminate this unique basin. In the present study birds' eggs (15
      species) collected in the Baikal region (Selenga river estuary) have been
      analysed. Quantitative determination of more than 40 individual organic
      pollutants (polycyclic aromatic hydrocarbons, phenols, organochlorine compounds)
      has been carried out using GC-MS as an analytical tool. The results obtained
      demonstrated a wide range of toxicant concentrations (2-3 orders of magnitude)
      for various species. Very high levels of polycyclic aromatic hydrocarbons have
      been detected in the eggs of Anas platyrynchos (mallard), Tringa stagnatilis
      (marsh sandpiper) and Podiceps auritus (slavonian grebe). These particular
      species also have the highest levels of other toxicants. Taking into account high
      rate of metabolism of certain of these compounds in birds, it has been proposed
      that the major route of transfer into higher trophic levels is via water and
      aquatic invertebrates.

PMID- 9573630
TI  - Serum selenium levels as indicators of body status in cancer patients and their
      relationship with other nutritional and biochemical markers.
AB  - A cross-sectional study of serum selenium levels in patients (n = 59) with
      different types of cancer from southeastern Spain was carried out using hydride
      generation atomic absorption spectrometry. The subjects were divided into four
      groups according to the cancer location (respiratory, digestive, haematological
      and gynaecological groups). Serum selenium levels in all patients (54.41 +/-
      24.80 mg/l) were significantly lower (P < 0.001) than those determined in control
      groups [healthy subjects from the same area (n = 130) and institutionalized
      elderly people (n = 93)]. Mean serum selenium concentrations were not
      significantly different among the four groups considered (P > 0.05). Linear
      regression analyses performed on serum selenium levels and biochemical markers
      (total cholesterol, triglycerides, transaminases, uric acid and urea) did not
      establish any statistically significant correlation (P > 0.05). No significant
      relationships between serum selenium concentrations and sex or age of patients
      was observed (P > 0.05). Given the marked overlap between the two ranges of the
      populations (the means are within approx. 1/2 S.D.) the predictive values of
      serum selenium are low. Thus, there is indeed a statistical significance between
      the means, but selenium cannot be used to determine whether or not a patient has
      cancer disease.

PMID- 9573631
TI  - Health and environmental benefits from air pollution reductions in Hungary.
AB  - The aim of this study was to assess the cost and benefit of the implementation of
      a specific energy saving program in Hungary. We have considered the possible
      reduced damage to public health, building materials and agricultural crops that
      may be obtained from reducing emissions of important air pollutants and also how
      the program contributes to reduced emissions of greenhouse gases. The measures
      are described in the National Energy Efficiency Improvement and Energy
      Conservation Programs (NEEIECP), elaborated by the Hungarian Ministry of Industry
      and Trade and accepted by the Government in 1994. The energy saving expected from
      the program is approximately 64 PJ/year. The benefits were estimated using
      monitoring data and population/recipient data from urban and rural areas in
      Hungary together with exposure-response functions and valuation estimates mainly
      from western studies. Our analysis indicates that the main benefit from reducing
      the concentrations of pollutants relates to public health and that reduced
      prevalence of chronic respiratory diseases is an important effect. Reduced
      premature mortality is also important and the estimated attributable risk of air
      pollution to excess mortality at present is approximately 6%. The estimated
      annual benefit of improved health conditions alone is likely to exceed the
      investments needed to implement the program. In addition there are significant
      benefits due to reduced replacement and maintenance costs for building materials
      (30-35 million US$ annually in Budapest only). The damage to crops due to ozone
      is large, but a significant improvement in Hungary depends upon concerted actions
      in several countries.

PMID- 9573633
TI  - Another dilemma.

PMID- 9573632
TI  - A Fourier transform infrared spectroscopic study of yeast hexokinase:
      conformational changes under interaction with substrates and inhibitors.

PMID- 9573634
TI  - Treatment models for clients with co-occurring addictive and mental disorders.
AB  - Recent epidemiologic studies conducted by the National Comorbidity Survey have
      indicated that up to 51% of individuals with a serious mental illness are also
      dependent on or addicted to illicit drugs. However, only 50% of these clients
      with cooccurring addictive and mental disorders receive treatment that addresses
      both issues. The author provides a historical overview of treatment philosophies
      and approaches, describes current treatment models, and reports on outcome data
      that describe the efficacy of current treatment. Recommendations are made for
      nurses to incorporate effective treatment models into nursing practice.

PMID- 9573636
TI  - Ethical considerations of video monitoring psychiatric patients in seclusion and
      restraint.
AB  - Video monitoring of psychiatric patients in seclusion and restraint is reviewed
      from ethical and legal perspectives. Video monitoring invades privacy beyond
      patient expectations for routine hospital care and has the potential to harm
      personal dignity. The potential benefit of patient safety through monitoring must
      be balanced with the potential harm of monitoring to provide ethical
      justification. Because involuntary monitoring places patients in a position of
      extreme vulnerability to personal exposure, clinicians are obligated to protect
      these patients. A case illustrating problems with video monitoring along with
      recommendations for ethical use of video monitoring are presented in this
      article.

PMID- 9573635
TI  - Addiction recovery for low-income pregnant and parenting women: a process of
      becoming.
AB  - A naturalistic field study of low-income women (N = 17) in an intensive
      outpatient addiction recovery program addressed the question: What is the nature
      of addiction recovery for pregnant and parenting-women in an addiction treatment
      program? Grounded theory methodology was used to determine the nature of the
      interpersonal and social processes that define addiction recovery for women in
      this study. Over 2 years, audiotaped semi-structured interviews, document reviews
      of medical records, treatment progress and group therapy notes, and participant
      observation notes were collected and analyzed. The constant comparison method of
      analysis involved an ongoing process of theoretical sampling, memoing, and open
      and then axial coding to identify, group, link, and reduce the categories
      produced. A developmental model of addiction recovery in pregnant and parenting
      women emerged that consisted of the dimensions of becoming drug and alcohol free,
      a partner in a relationship, a person, and a parent. These four dimensions
      parallel and transform each other, yielding different outcomes but similar
      patterns over time. This model of addiction recovery provides a beginning
      framework for understanding the transactional nature of addiction recovery for
      low-income women who are adapting to a drug and alcohol-free lifestyle and the
      task and role of parenting a newborn.

PMID- 9573637
TI  - A restraint on restraints: the need to reconsider the use of restrictive
      interventions.
AB  - Children with behavior problems are put in units with milieu therapy for the
      support and guidance of a specialized health care team, supposedly experts in the
      care of children with these unique and urgent needs. The reality of such units,
      however, is that those with the most contact with the children are often
      inadequately prepared, both in terms of knowledge and skills, to manage
      disruptive behaviors. As a result, the milieu that is supposed to provide support
      and structure can actually exacerbate the trauma for the vulnerable child.
      Preliminary data are presented from an ongoing study that is investigating the
      experiences and memories of formerly hospitalized children. Three types of
      traumatic experiences are described: vicarious trauma, alienation from staff, and
      direct trauma. Many of the traumatic events endured by child patients are the
      result of an inappropriate use by staff of power and force. There was a marked
      lack of understanding by the children of why given interventions were used.
      Although coercive interventions are sometimes necessary, ethical, legal, and
      other professional considerations make it clear that more work is needed.
      Research to identify the patterns of lack of knowledge and skills, as well as to
      develop appropriate interventions are recommended.

PMID- 9573638
TI  - Perseverance: the meaning of patient education in psychiatric nursing.
AB  - This phenomenological study was undertaken to discern the meaning psychiatric
      nurses attach to their patient education experiences. Although patient education
      crosses all nursing specialty areas, no studies have attempted to describe how it
      is unique to psychiatric nursing. Hermeneutic analysis of audiotaped,
      semistructured, in-depth interviews revealed three themes, The Teaching Way,
      Being In-Between, and Seeing Inside, which, when taken together, formed one
      constitutive pattern: perseverance. The results indicate that psychiatric nurses
      are very much involved in educating their patients and that the process differs
      from traditional expectations of learning readiness. There is also an apparent
      need to educate students about the realities of health care settings and how to
      deal with them. The researcher, herself a psychiatric nurse, came away from this
      study with a renewed respect for nurses' commitment to patient education, for
      their ability to use themselves as therapeutic tools, and for their ability to
      practice from within political settings which seldom encourage or reward nurses
      for patient education. Further studies are needed to explore how nurses deal with
      the political realities affecting their practices and how they maintain their
      commitment to patient care under such circumstances.

PMID- 9573639
TI  - A comparison of heterosexual and homosexual long-term sexual relationships.
AB  - This is a study of a nonrandom sample of 94 women who are in long-term sexual
      relationships. The women were divided into groups of heterosexual and homosexual
      women who reported childhood sexual abuse, and heterosexual and homosexual women
      who reported no history of childhood sexual abuse. The groups were rated
      according to their levels of sexual satisfaction and relationship satisfaction.
      Results indicate that women who have not been abused are more satisfied with
      their relationships than women who have been abused. Heterosexual and homosexual
      women who have a history of childhood sexual abuse are less satisfied with their
      sexual relationships than women without histories of abuse. However, homosexual
      women who have been abused rated their relationship satisfaction higher than
      heterosexual women who have been abused. By showing that one cannot draw
      conclusions about homosexual women based on research on heterosexual women, this
      study encourages further research to enable nurses to refine their care planning.

PMID- 9573640
TI  - Benzodiazepine-induced persisting amnestic disorder: are older adults at risk?
AB  - Currently there are approximately 31.5 million Americans 65 years and older. This
      number is expected to reach 39.3 million by 2010. This group represents 12% of
      the population, however, they use 25% to 40% of the prescription medications,
      averaging 4.5 medications daily; 75% of them use over-the-counter medications as
      well. This population has also experienced an increase in the prescription of
      central nervous system (CNS) medications. Benzodiazepines are the most widely
      prescribed class of CNS antianxiety/sedative medication. This article examines
      the use of benzodiazepines in relation to physiological, pharmacokintic, and
      pharmacodynamic changes of the older adult. The amnestic properties of these
      drugs in relation to the already decreasing cognitive function of the older adult
      are explored in relationship to the Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition, criteria for substance-induced persisting amnestic
      disorder.

PMID- 9573641
TI  - Preliminary results from a twin study of infant--caregiver attachment.
AB  - Two pilot studies were conducted. First, the validity of a measure of infant
      caregiver attachment for twins was assessed. Sixteen twin pairs from the
      Louisville Twin Study (LTS) were assessed in the Strange Situation (SS) at ages
      19 or 25 months. Concordance between the LTS procedure and the SS procedure for
      assessing attachment was 78.1%, significantly greater than chance. Second, twin
      similarity for attachment as measured by the LTS procedure was assessed.
      Videotapes of 34 MZ pairs and 26 DZ pairs at ages 18 and 24 months were rated in
      terms of attachment behavior. MZ concordance for attachment was 67.6%,
      significantly greater than the DZ concordance rate of 38.5%. Results are
      discussed in the context of current debate in attachment theory.

PMID- 9573642
TI  - Genetic influences on EEG coherence in 5-year-old twins.
AB  - Electroencephalographic (EEG) coherence has been suggested to be an index of the
      connectivity of the brain. It represents the coupling between two EEG signals
      from different brain areas and is mathematically analogous to a cross-correlation
      in the frequency domain. We obtained data from 167 pairs of 5-year-old twins to
      study genetic and environmental influences on individual differences in
      intrahemispheric coherences. Coherence was computed in the theta band (4.0 to 7.5
      cycles/s) between prefrontal, frontal, central, parietal, and occipital regions
      during quiet rest. Univariate genetic analyses of the data showed moderate to
      strong genetic influences for all coherences. Broad heritabilities ranged from 30
      to 71%, with a mean heritability of 49%. With one exception, no sex differences
      were found. Split-half reliabilities varied with interelectrode distances,
      ranging from .91 for the shortest distance to .62 for the longest distance. When
      split-half reliabilities are compared with heritabilities, the data suggest that
      for corticocortical connections between adjacent brain areas, a large part of the
      variance is explained by "true" environmental influences, whereas for longer
      connections, that is, sensory to frontal areas, the variance is mostly genetic in
      origin.

PMID- 9573643
TI  - A comparison of adult female twins from opposite-sex and same-sex pairs on
      variables related to reproduction.
AB  - In several litter-bearing species, prenatal exposure of a female fetus to
      hormones from adjacent male fetuses can lead to later effects on various
      anatomical and behavioral characteristics of the female, including a number
      related to reproduction. To see if such traits are also affected in humans, adult
      female twins from a large Australian sample who had male cotwins were compared to
      females with female cotwins on 90 questionnaire items related to reproductive
      functions. No substantial effects could be clearly demonstrated, although some
      weak effects remained a possibility. Some variables, such as age at first
      menstruation, age at first pregnancy, and height, were consistent in direction
      with results from the animal literature, although the effect sizes were small and
      not statistically significant.

PMID- 9573644
TI  - Effect of within-strain sample size on QTL detection and mapping using
      recombinant inbred mouse strains.
AB  - Increasing the number of mice used to calculate recombinant inbred (RI) strain
      means increases the accuracy of determining the phenotype associated with each
      genotype (strain), which in turn enhances quantitative trait locus (QTL)
      detection and mapping. The purpose of this paper is to examine quantitatively the
      effect of within-strain sample size (n) on additive QTL mapping efficiency and to
      make comparisons with F2 and backcross (BC) populations where each genotype is
      represented by only a single mouse. When 25 RI strains are used, the estimated
      equivalent number of F2 mice yielding the same power to detect WTLs varies
      inversely as a function of the heritability of the trait in the RI population
      (hRI2). For example, testing 25 strains with n = 10 per strain is approximately
      equivalent to 160 F2 mice when hRI2 = 0.2, but only 55 when hRI2 = 0.6. While
      increasing n is always beneficial, the gain in power as n increases is greatest
      when hRI2 is low and is much diminished at high hRI2 values. Thus, hRI2 is high,
      there is little advantage of large n, even when n approaches infinity. A cost
      analysis suggested that RI populations are more cost-effective than conventional
      selectively genotyped F2 populations at hRI2 values likely to be seen in
      behavioral studies. However, with DNA pooling, this advantage is greatly reduced
      and may be reversed depending on the values of hRI2 and n.

PMID- 9573645
TI  - Mapping of provisional quantitative trait loci influencing temporal variation in
      locomotor activity in the LS x SS recombinant inbred strains.
AB  - The finding that stress-induced locomotor activity exhibited a significant strain
      x time interaction in the LS x SS RI strains prompted examination of QTL
      influencing this behavior as a function of time. The degree of genetic
      determination for locomotor activity was 0.26 for the first 5 min and decreased
      to 0.16 for the last 5 min of a 30-min test but the number of genetic factors
      stayed relatively constant (three or four) across time. A QTL point analysis
      revealed a total of 15 QTL, 5-8 per 5-min time block. Few of the QTL were
      detected across all time points and different combinations of QTL were evident
      for each time period. Five of the QTL were in common with those reported by other
      investigators for similar behaviors. The results suggest that locomotor behavior
      is under a greater degree of genetic control during the initial part of the test
      but environmental factors become increasingly important as the test progresses.
      Furthermore, different genetic factors appear to be mediating genetic variation
      in locomotor behavior at any given time point.

PMID- 9573646
TI  - Discovery of a new Pomc1 allele in the LS x SS recombinant inbred strains:
      relationship to locomotor behavior.
AB  - Various lines of evidence suggest that a polymorphism in the gene for
      proopiomelanocortin, Pomc1, might account for some portion of the genetic
      variance for open-field activity in the LS x SS RI strains. To test this
      hypothesis, approximately 1600 bp of Pomc1 was sequenced from genomic DNA of
      seven of the LS x SS strains. Two distinct alleles containing a total of five
      single-base pair differences were detected. A substitution was found in the
      coding region causing a Pro-to-Ser conversion, two substitutions occurred in the
      3' untranslated region of the mRNA, and a substitution and a deletion were
      detected in the 3' untranscribed flanking region. The fragment containing the
      coding region substitution was sequenced in an additional 15 of the LS x SS
      strains. A total of 12 strains contained one form of the allele, while 10 had the
      other. The strain distribution pattern of open-field activity scores between the
      two allels suggests that these alleles do not contribute to the genetic variation
      of open-field activity in the LS x SS RI strains.

PMID- 9573647
TI  - Developmental isolation and subsequent adult behavior of Drosophila paulistorum.
      IV. Courtship.
AB  - Early social experiences play important roles in adult Drosophila paulistorum
      mate selection. Differences in courtship between control males and wholly
      socially isolated males were observed in chambers. Socially isolated males
      displayed more courtship toward virgin females than did controls. Socially
      isolated males were more successful in competing for mates. Yet socially isolated
      males from all six semispecies also displayed notable frequencies of homosexual
      behavior.

PMID- 9573648
TI  - Genetic variability of conditioned probing responses to a fruit odor in
      Leptopilina boulardi (Hymenoptera: Eucoilidae), a Drosophila parasitoid.
AB  - The genetic variability of odor-conditioned probing behavior was investigated in
      a population of Leptopilina boulardi, a parasitoid of Drosophila larvae.
      Ovipositor probing is the final step of host location, leading to the discovery
      of host larvae. It can be triggered by an odor previously experienced during an
      oviposition as a result of associative learning. This study was based on the
      analysis of female probing performance over two generations of isofemale lines
      (using both mother-daughter regressions and one-way analysis of variance).
      Individual performances of the conditioned response to the odor were
      characterized by (1) the latency (i.e., the time elapsed between the onset of the
      odor delivery and the start of the probing response), (2) the duration of the
      first probing phase, and (3) the total probing duration. Results suggested that
      the variability of two characters, the latency and the duration of the first
      probing phase, were under a genetic control in the studied population. This work
      is the first contribution to quantify the genetic component of this variability.

PMID- 9573649
TI  - Pre-discharge outcomes of 22-27 weeks gestational age infants born at tertiary
      care centers in Connecticut implications for perinatal management.
AB  - There is a lack of regional data on survival and morbidity of extremely premature
      infants born and resuscitated at tertiary care centers. This study analyzes such
      data from three tertiary care perinatal centers in Connecticut and provides a
      paradigm for its use in developing guidelines for evidence-based ethical
      considerations in infants at the threshold of viability. Outcomes of inborn
      infants 22 to 27 weeks gestation (based on obstetric estimates) who were actively
      resuscitated at three regional perinatal tertiary-care centers (representing 80%
      of such infants from Connecticut) were studied retrospectively. Survival and
      cumulative major morbidities at discharge, stratified by gestational age, were
      analyzed. Of the 405 infants studied, 278 (69%) survived to discharge. There were
      no survivors beyond three days at 22 weeks gestational age. Unfavorable outcome
      defined as death or major morbidity (> or = grade 2 intraventricular hemorrhage,
      periventricular leukomalacia, > or = Stage 3 retinopathy of prematurity,
      necrotizing enterocolitis > or = Stage 2, and severe bronchopulmonary dysplasia
      at 36 weeks postmenstrual age.) was seen in > 85% of 23 and 24 weeks gestation
      infants. At 25 weeks approximately equal to 30% of infants were discharged
      without an unfavorable outcome. At 26 and 27 weeks gestation 43% and 61%
      respectively escaped unfavorable outcomes with > 85% rates of survival. Current
      regional data such as these would help in developing guidelines for the perinatal
      management of premature infants at the threshold of viability.

PMID- 9573650
TI  - Teaching care of terminally ill patients: a primary care perspective.
AB  - Currently there is a great interest in educating medical students in the care of
      patients with terminal illness. When medical students do encounter patients with
      terminal illness, it is often in the acute care setting. We have designed a
      workshop for fourth-year medical students who are working in general medical,
      family, or pediatrics practices as part of their month-long primary-care
      clerkship. The emphasis of this workshop is on the care of the terminally ill
      patient as a natural extension of the continuum of care offered by a primary-care
      physician. The workshop involves an interactive interview of a patient with a
      terminal illness by a group of four to eight students and the guidance of an
      experienced physician facilitator. Four themes are identified as central to the
      primary care of patients with terminal illness, and emphasis is placed on
      communication skills and the meaning of language to the dying patient.

PMID- 9573651
TI  - Frequency of breast biopsy and breast cancer diagnosis in central Connecticut-
      trends from 1993 to 1997.
AB  - The frequency of diagnosed breast cancer at Hartford Hospital has risen 75% from
      1993 to 1997 (153 vs 87 cases during January-March 1997 as compared to January
      March 1993). During the same intervals the frequency of breast biopsies performed
      also increased 45% (455 vs 312 biopsies). The rate of "positive" biopsies has
      increased slightly (27.9%, 28.3%, 31.5%, 30.7%, and 33.6% for the first three
      months of each year 1993 to 1997, respectively). When stratified into thirds
      based on decreasing practice activity of Hartford Hospital surgeons with regard
      to breast surgery, the "positive" biopsy rates were 28.7%, 31.2%, and 33.0%
      respectively. Local breast cancer incidence is rising, however surgeons are not
      "overusing" breast biopsy as compared to recent past practice despite the fact
      that many more breast biopsies are now being performed.

PMID- 9573652
TI  - Primary health-care physicians: vital roles in organ and tissue donation.
AB  - The involvement of primary-care physicians is integral to the success of organ
      and tissue donation and transplantation. Primary-care physicians have a vital
      role to play in educating patients and encouraging family discussion about organ
      and tissue donation. A study to determine the practice of Connecticut primary
      care physicians relative to providing donation information to patients during
      routine care was conducted in three phases: 1) validation of current practice of
      primary-care physicians regarding educating patients about donation, 2)
      development and distribution of educational materials requested by primary-care
      physicians, 3) evaluation of primary-care physician practice and educational
      materials. Most (69% N = 310) responding primary-care physicians never discuss
      organ/tissue donation with patients during routine care and only 5% (N = 24) had
      donation information available. When provided with donation materials, most
      primary-care physicians left these materials in the waiting room and did not
      personally discuss donation with the patient. Collaboration between primary-care
      physicians and organ procurement staff needs to be increased so that primary-care
      physician's more readily discuss donation with their patients and encourage
      patients to discuss donation decisions with family members.

PMID- 9573653
TI  - Formulary review of the carbapenems: comparison of imipenem/cilastatin and
      meropenem.
AB  - In comparison with imipenem, meropenem exhibits closely similar microbiological
      activity. Although meropenem has slightly greater gram-negative activity against
      organisms, like Pseudomonas aeruginosa and Burkholderia cepacia, imipenem
      demonstrates more intense gram-positive activity, particularly towards
      Enterococcus faecalis which may reduce or even cancel out, the clinical relevance
      of these microbiological differences. However, an aminoglycoside is usually added
      in the treatment of serious infections from these bacteria. The pharmacokinetics
      of these two agents are also closely similar both in normal healthy volunteers
      and in patients with normal or impaired renal function. Moreover, there is
      little, if any, difference in the acquisition costs for meropenem and imipenem in
      most hospitals. Cost-avoidance with meropenem is, therefore, mainly the result of
      less frequent dosing and the ability to administer meropenem by rapid intravenous
      injection. Additionally, meropenem's FDA approved indication for central nervous
      system infection offers an additional advantage when compared to
      imipenem/cilastatin. It was for these reasons that our hospital's Pharmacy and
      Therapeutics Committee replaced imipenem/cilastatin with meropenem.

PMID- 9573654
TI  - Assistance with suicide.

PMID- 9573656
TI  - In response to "outbreak of staphylococcal food poisoning associated with
      precooked ham--Florida, 1997".

PMID- 9573655
TI  - In response to Connecticut College of Emergency Physicians' abstract by Drs. Daly
      and Reiser.

PMID- 9573657
TI  - Is there a place for hospitalists in health-care reform?

PMID- 9573658
TI  - Successful aging.

PMID- 9573659
TI  - A logistic model of the seasonal migration decision for elderly households in
      Arizona and Minnesota.
AB  - While most previous studies of elderly migration have investigated permanent
      migration using Census data, this paper employs household (micro) data from
      statewide surveys conducted in Arizona and Minnesota to analyze seasonal
      migration as an economic decision. Estimation of logistic regression models for
      each state indicate income and age are important determinants, whereas these
      variables have not proven significant in previous studies based on aggregate
      data. The results lead to the conclusion that seasonal migration may be an
      integral part of a life cycle of elderly migration.

PMID- 9573660
TI  - Discretion and service use among older adults: the behavioral model revisited.
AB  - Research applying the behavioral model to the use of services among older adults
      could be enriched by the classification of services along a discretionary
      dimension. Survey responses from 2,178 community-dwelling older adults were used
      to test the hypothesis that predisposing, enabling, and need characteristics are
      better predictors of discretionary than nondiscretionary service use. Logistic
      regression results predicting the use of a variety of community-based and medical
      services categorized as most discretionary, partially discretionary, and least
      discretionary generally support our hypothesis, underscoring the importance of
      need characteristics for least discretionary service use.

PMID- 9573661
TI  - Emerging concerns of older stroke patients about assistive device use.
AB  - Assistive devices minimize limitations from physical impairment and are integral
      to rehabilitation. Little is known about older patients' concerns, perceptions,
      and beliefs about assistive devices. This study used a structured, qualitative
      approach to describe device perceptions of 103 stroke patients in rehabilitation.
      Six dimensions of patient concerns were identified, including the operation and
      utility of devices, social contexts and consequences, and attributions of
      cultural meanings of use. Initial device use posed cultural value dilemmas
      originating in discrepancies between sociocultural beliefs and conflicting
      normative expectations. Knowledge of these dimensions suggests new areas for
      social science research and refinements to clinical practice.

PMID- 9573662
TI  - Characteristics of nursing homes that are restraint free.
AB  - Using nationally representative data from the On-line Survey and Certification of
      Automated Records (OSCAR) and the Area Resource File (ARF), comprising 15,074
      nursing homes, the differences between restraint free and non-restraint free
      nursing homes were examined. Restraint free nursing homes were found more likely
      to have residents with less ADL deficiencies and lower average numbers of
      residents who were bowel or bladder incontinent. They were more likely to be not
      for-profit, smaller, low occupancy facilities that did not belong to nursing home
      chains, and were located in urban and more competitive areas. With regard to
      staffing factors, restraint free facilities had a richer mix of nursing staff,
      although the total number of staff per resident did not differ. Restraint free
      facilities were likely to utilize more full-time equivalent (FTE) registered
      nurses (RNs) per resident, but less FTE nurse aides and licensed practical nurses
      (LPNs) per resident. Psychoactive drug use rates did not differ between the types
      of homes.

PMID- 9573663
TI  - Correlates of disruptive behavior in severely cognitively impaired nursing home
      residents.
AB  - This article provides information about correlates of "disruptive behaviors"
      among nursing home residents with dementia. We used averages of multiple
      observations for a wide range of behaviors (n = 45) across 11 months to gather
      this information. We placed behaviors into four separate categories: physically
      aggressive, physically non-aggressive, vocally agitated, and vocally aggressive.
      Then, we tested associations between these categories and demographic, cognitive,
      and health variables. Cognitive status and selected demographic variables were
      associated with the behavior categories; adding health variables did not improve
      prediction. Lower cognitive status was associated with more disruptive behaviors.
      Our findings suggest that cognitive status, but not health variables, predicts
      disruptive behavior among nursing home residents with dementia.

PMID- 9573665
TI  - The relationship of demographic factors, locus of control and self-efficacy to
      successful nursing home adjustment.
AB  - This study investigated demographic and psychological predictors of 58 older
      adults' successful adjustment to a nursing home. Predictors included demographic
      variables, locus of control, and self-efficacy beliefs. Successful adjustment was
      defined by activity level and by positive and negative affect. Findings suggest
      that demographic variables were not effective predictors of successful
      adjustment. Perceived self-efficacy accounted for more of the unique variance in
      adjustment than locus of control. Results are discussed in the context of
      improving resident adjustment to nursing home environments.

PMID- 9573664
TI  - The effects of an enhanced environment on nursing home residents who pace.
AB  - This study sought to enhance the well-being of older nursing home residents who
      pace and wander by enriching their nursing home environment. Visual, auditory,
      and olfactory stimuli were added to the nursing home unit environment to simulate
      two types of environments: a home environment and an outdoor nature environment.
      Participants seemed to prefer the enhanced environments by choosing to spend more
      time in them, and by sitting on benches in those environments. There was a trend
      toward less trespassing, exit-seeking, and other agitated behaviors being
      exhibited in the enhanced environment, and residents were observed to manifest
      more pleasure in it. Staff members and family members definitely expressed a
      preference for the enhanced environment over the regular one. Although effects on
      residents were limited, this approach offers a low-cost method for making the
      nursing home environment a better place for those residents.

PMID- 9573666
TI  - Stability of preferences for treatment among nursing home residents.
AB  - This study assessed the stability of nursing home residents' preferences for
      medical treatments. Thirty-seven nondemented, nondepressed residents were
      surveyed serially over a six-month period. Preferences were elicited for CPR,
      i.v. antibiotics, mechanical ventilation, and artificial nutrition. Subjects
      preferred more treatment for their current health concerns than for all
      hypothetical conditions (p = .001). Subjects disvalued indefinite artificial
      nutrition and mechanical ventilation compared to time-limited trials (p < .001).
      All preference changes were toward less intervention; residents preferred limited
      treatment. Most preferences remained stable. Residents clearly distinguished
      between time-limited and indefinite treatment, desired i.v. antibiotics and
      limited mechanical ventilation, and rejected most other treatments.

PMID- 9573667
TI  - Differences in the perceived well-being of wives and husbands caring for persons
      with Alzheimer's disease.
AB  - This study aimed to examine differences in subjective psychological well-being
      between husband and wife caregivers of persons with Alzheimer's disease in
      comparison to the psychological states of noncaregiver husbands and wives similar
      in age and ethnicity. The principal comparison of interest was whether
      differences between husband and wife caregivers were greater than those between
      comparison group husbands and wives. Significant interactions for six out of nine
      psychological measures indicate that gender-related differences between spouse
      caregivers were specifically associated with the caregiving role. Possible
      explanations for the discrepancy between husband and wife caregivers as well as
      practice implications are discussed.

PMID- 9573668
TI  - Who supports whom? How age and gender affect the perceived quality of support
      from family and friends.
AB  - This study investigates age and gender differences in the relative perception of
      social support across adulthood. Findings indicate that age and gender do affect
      both the perception of positive support and the perception of demandingness
      across different support relationships. In all age groups, men appear to perceive
      spousal support as the most positive, while women seem to perceive the support
      received from children as being the most positive. However, it is apparent that
      all three relationships studied--those with spouse, children, and friends/other
      relatives--are important sources of support for both men and women.

PMID- 9573669
TI  - The provision of informal support by elderly people residing in assisted living
      facilities.
AB  - This study examined factors facilitating support giving to members of the social
      network by elderly Jewish persons residing in assisted living facilities in
      Israel. A support provision score was regressed on two sets of background control
      variables: personal characteristics and housing factors; social network
      variables; and an exchange measure-perceived available support. The hierarchical
      multivariate results revealed that it was principally the perceived support
      measure along with two personal characteristics (younger age and nonreligious
      orientation) that explained the variance in the support provision score (R2 =
      .52). The findings underscore the importance of reciprocity within the informal
      networks of this population.

PMID- 9573670
TI  - Factors associated with symptoms of depression among informal caregivers of
      demented elders in the community.
AB  - This study assessed variables associated with increased severity of depressive
      symptoms among 321 informal caregivers of demented subjects living in the
      community identified by a Canadian national population-based survey. Measures
      included patient and caregiver demographic variables; patient behavioral
      disturbance, activities of daily living, and cognitive impairment; living
      arrangement, and duration of disease. Depressive symptoms were measured with the
      Center for Epidemiologic Studies Depression Scale (CES-D). Multiple regression
      analyses indicated that a higher CES-D score was significantly associated with
      three caregiver characteristics (being a spouse or child of the patient, self
      identified ethnicity other than English and French Canadian, and lower
      education), and two patient characteristics (greater behavioral disturbance and
      moderate to severe functional impairment).

PMID- 9573671
TI  - Randomized clinical trials in adult acute lymphoblastic leukemia: which is the
      question?

PMID- 9573672
TI  - Flow cytometric characterization of human umbilical cord blood lymphocytes:
      immunophenotypic features.
AB  - BACKGROUND AND OBJECTIVE: One of the most important potential advantages in the
      use of human umbilical cord blood (HUCB) for hematopoietic reconstitution after
      myeloablative therapy seems to be the lower occurrence of acute graft-versus-host
      disease (GvHD) in recipients after allogeneic transplantation. Since mature T
      cells play an important role in GvHD pathogenesis, we tried to verify whether a
      different immunophenotypic pattern exists between HUCB and peripheral blood (PB)
      T cells. DESIGN AND METHODS: An immunophenotypic study on 40 HUCB and 40 PB
      samples from healthy adult volunteers was performed, by means of flow cytometry
      using a large panel of monoclonal antibodies in double labeling. RESULTS: The
      absolute lymphocyte count was greater in HUCB (5233 +/- 1808 microL) than in
      adult PB (1941 +/- 378 microL). Significant differences in percentage were found
      between cord and adult T-cells, respectively (CD3+: 59.9 +/- 12 vs 74.9 +/-
      4.6%), CD3- CD16+ and/or CD56+ natural killer (NK) cells (23.8 +/- 10.1 vs 10.8
      +/- 5.3%) and CD3+CD16+ and/or CD56+ cytotoxic T lymphocyte subset (0.3 +/- 0.3
      vs 10.7 +/- 4.1%). There was no difference in CD4/CD8 ratio (1.7 +/- 0.5 vs 1.6
      +/- 0.2%) between the two groups. In absolute terms, HUCB contained an higher
      number of all lymphocyte subsets, with the exception of CD3+CD16+ and/or CD56+ T
      lymphocyte subpopulation, CD3+CD25+ and CD3+HLADR+ activated T-cells. CD38, a
      marker of activation and immaturity, was present on virtually all cord T cells
      and on approximately half of the adult T cells. The large majority of HUCB T
      cells co-expressed CD45RA naive antigen (CD4+CD45RA+: 87.6 +/- 5.2%, CD8+
      CD45RA+: 93.5 +/- 7.8%; CD4+CD45RO+: 12.3 +/- 5.2%; CD8+CD45RO+: 6.4 +/- 7.8%)
      whereas in adult PB T cells an higher number of CD45RO+ memory cells was detected
      (CD4+CD45RA+: 44.8 +/- 9.6%; CD8+CD45RA: 71.5% +/- 8.1%; CD4+CD45RO+: 55.2 +/-
      9.6%; CD8+ CD45RO+: 28.5 +/- 8.1%). Finally, less than 14% of lymphocytes were
      shown to belong to B lineage in both sources, while, in absolute terms, they were
      more represented in HUCB with respect to adult PB. INTERPRETATION AND
      CONCLUSIONS: In the present study we found significant difference between HUCB
      and adult PB lymphocytes in their immunophenotypic profile. In particular HUCB
      showed T lymphocytes that appeared to be phenotypically immature. Indeed, as a
      likely consequence of poor antigenic experience during pregnancy, the majority of
      HUCB cells were naive, expressing the RA isoform of the CD45 molecule. These
      findings could justify the previously reported reduced cord blood lymphocyte
      alloreactivity when allogeneic transplantation is performed and require further
      functional studies in order to confirm the impairment of HUCB immune system
      response to alloantigens.

PMID- 9573673
TI  - Mobilized peripheral blood CD34+ cells express more amphotropic retrovirus
      receptor than bone marrow CD34+ cells.
AB  - BACKGROUND AND OBJECTIVE: The increased susceptibility to gene transfer by
      amphotropic retroviral vectors of mobilized peripheral blood (PB) CD34+ cells
      compared to their bone marrow (BM) counterparts may depend, among other factors,
      on the level of expression of the amphotropic receptor on the progenitor cell.
      Using a previously described flow cytometry strategy, we have studied retrovirus
      binding to mobilized CD+ cells, derived from cancer patients treated with high
      dose chemotherapy and growth factor(s), that are efficiently transduced by N2
      retrovirus vector. DESIGN AND METHODS: We measured the binding of the retrovirus
      to the cells using a rat monoclonal antibody reactive with the gp70 envelope
      glycoprotein, common to all replication-defective amphotropic retroviruses.
      Antibody-virus-cell complexes were indirectly labeled and analyzed by flow
      cytometry. We compared the binding of PA317-N2 vector to CD34+ cells derived from
      steady-state BM, steady-state PB and mobilized PB from cancer patients treated
      with high-dose chemotherapy and cytokine. RESULTS: The fluorescence intensity of
      mobilized CD34+ cells was approximately one log higher than that of steady-state
      BM or PB CD34+ cells, indicating that the expression of the amphotropic receptor
      was increased. Moreover, the virus binding was proportional to the gene transfer
      rate, as assessed by G418 resistance into mobilized PB-derived CFU-GM. The
      increase in fluorescence intensity appeared to be restricted to CD34+ cell
      subset, neither CD2+ nor CD14+ cells bound the virus in an appreciable amount.
      INTERPRETATION AND CONCLUSIONS: Virus binding, as assessed by indirect
      immunofluorescence assay, is increased in mobilized CD34+ cells. The increased
      binding may contribute to their high susceptibility to retrovirus vector
      infection.

PMID- 9573674
TI  - Detection of single and associated lesions of the Bcl-1, Bcl-2, Bcl-6, c-myc, p53
      and p16 genes in B-cell non-Hodgkin's lymphomas: value of molecular analysis for
      a better assignment of the histologic subtype.
AB  - BACKGROUND AND OBJECTIVE: Molecular genetic abnormalities have been frequently
      described in non-Hodgkin's lymphomas (NHL). These lesions have been associated
      with specific entities, allowing a better categorization of NHL. However, these
      abnormalities are not as specific as initially described and their association is
      still unknown. DESIGN AND METHODS: By Southern blot and polymerase chain
      reaction, we have simultaneously analyzed the proto-oncogenes Bcl-1, Bcl-2, Bcl
      6, c-myc and MLL and the tumor suppressor genes p53 and p16, in 100 unselected B
      cell NHL patients at diagnosis, to establish its incidence throughout the
      different NHL subtypes, defined both by Working Formulation and REAL
      classifications, and to assess the frequency of co-existence of two or more
      genetic lesions within each individual patient. RESULTS: Fifty two cases
      displayed some genetic abnormality. Bcl-1, altered in 12 cases, was highly
      specific to mantle cell lymphomas (57% of them), but 6 cases had a different
      histologic subtype. Bcl-2 was rearranged in 26 cases: 70% in follicular lymphomas
      (FL) and 20% in diffuse large cell lymphomas; these abnormalities were also
      present in other subtypes, i.e. marginal lymphomas (30%). Bcl-6 abnormalities
      were mostly found in diffuse large cell lymphomas (29%) but also found in other
      subgroups, like FL (14%). C-myc rearrangements were specific to Burkitt's
      lymphoma. MLL gene was always germline. Deletions and/or rearrangements of p53
      and p16 genes were rare (4% and 8% of all cases, respectively). Finally,
      association of genetic lesions was a relatively common finding (13% of cases),
      especially in cases with adverse prognostic morphologies according to the REAL.
      INTERPRETATION AND CONCLUSIONS: Molecular abnormalities are frequent in NHL at
      diagnosis, not only as unique lesions but also associated. A relative high
      specificity of some alterations was seen, thereby contributing to a better
      assessment of the histological subtype.

PMID- 9573675
TI  - Weekly administration of vincristine, cyclophosphamide, mitoxantrone and
      bleomycin (VEMB) in the treatment of elderly aggressive non Hodgkin's lymphoma.
      Gruppo Italiano per lo Studio dei Linfomi.
AB  - BACKGROUND AND OBJECTIVE: Aim of the study was to assess the efficacy of VEMB, a
      short-lasting therapeutic regimen (50 days) which alternates two myelotoxic drugs
      (cyclophosphamide and mitoxantrone) every week with two less hematologically
      toxic drugs (vincristine and bleomycin) in the treatment of aggressive NHL in the
      elderly (over 70). DESIGN AND METHODS: Between November 1994 and March 1996, 37
      patients aged more than 70 years, with highly or moderately malignant NHL
      (according to the Working Formulation) have been enrolled into the study. The
      stage of the disease ranged between II and IV according to Ann Arbor. Mean age
      was 77 years; 14 patients (38%) had stage IV; 19 patients (51%) had LDH higher
      than normal; 26 patients (70%) had extranodal and 9 patients (24%) had bulky
      disease at time of diagnosis. RESULTS: Sixty-two percent of patients achieved a
      complete and 22% a partial remission. Non-responders amounted to 5%. Four
      patients (11%) died during the therapy. Nine patients (24%) experienced grade III
      IV neutropenia. The most frequently observed event was mild neurotoxicity (43% of
      cases). The overall survival rate at 30 months was 55%. DFS at 24 months was 66%.
      INTERPRETATION AND CONCLUSIONS: VEMB is a therapeutic regimen whose efficacy is
      comparable to that of the other derived MACOP-B therapeutic regimens used in the
      elderly NHL. It has proved to have a good feasibility, though the number of toxic
      deaths should not be neglected.

PMID- 9573676
TI  - Late intensification chemotherapy has not improved the results of intensive
      chemotherapy in adult acute lymphoblastic leukemia. Results of a prospective
      multicenter randomized trial (PETHEMA ALL-89). Spanish Society of Hematology.
AB  - BACKGROUND AND OBJECTIVE: Intensive induction and post-remission therapies have
      improved the prognosis in adult acute lymphoblastic leukemia (ALL). However,
      different from children, the impact of late intensification therapy in the
      overall results of treatment has not been consistently evaluated. The objective
      of this study was to analyze the results of a multicenter prospective protocol,
      PETHEMA ALL-89, in which, after intensive induction and consolidation therapy,
      randomization to receive delayed intensification treatment was performed. DESIGN
      AND METHODS: One hundred and eight adults (age > or = 15 years) diagnosed with
      ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with
      a five-drug induction therapy, followed by four cycles of early post-remission
      treatment during four months, and maintenance therapy for two years. Patients in
      remission at the end of the first year were randomized to receive one six-week
      cycle of late intensification therapy. Uni- and multivariate analyses of early
      response to treatment, complete remission (CR), leukemia-free survival (LFS) and
      overall survival (OS) were performed. RESULTS: The median (range) age of the
      series was 28 (15-74) years and leukocyte count 26 x 10(9)/L (1-600). ALL L1/L2
      was present in 38/70 patients, early pre-B in 13, common in 53, pre-B in 12 and T
      in 30 cases. The CR rate was 86%, and refractory disease 9%. Median LFS was 34
      months, with a 5-yr probability of 41% (95% CI, 29-53), whereas median OS was 51
      months and 5-year probability 47% (34-59%). There were no differences in either
      LFS and OS between patients who did or did not receive delayed intensification
      therapy. Prognostic factors for CR attainment were advanced age and slow response
      to therapy. These two features were, in addition to high leukocyte counts, the
      parameters with negative influence in both LFS and OS. INTERPRETATION AND
      CONCLUSIONS: The results of PETHEMA ALL-89 are similar to those referred in other
      chemotherapy-based protocols in adult ALL. Delayed intensification has not
      improved the length of remission and survival. Efforts to improve the prognosis
      of adult ALL patients must be mainly focused in early intensification treatment.

PMID- 9573677
TI  - Prior treatment with alpha-interferon does not adversely affect the outcome of
      allogeneic BMT in chronic phase chronic myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVE: Controlled clinical trials have shown that Interferon
      alpha (IFN-alpha) is able to control myeloid proliferation and to suppress the
      Ph+ clonal hemopoiesis in early chronic phase chronic myeloid leukemia (CML): a
      growing number of patients are treated with this agent from diagnosis. However,
      if a CML patient has an HLA-identical sibling, bone marrow transplant (BMT)
      represents the best choice of treatment. Since IFN-alpha is known to modify the
      immunologic response and to increase marrow fibrosis, information is needed on
      the outcome of patients transplanted after IFN-alpha treatment. DESIGN AND
      METHODS: We analyzed retrospectively 32 Ph+ CML patients submitted to BMT in the
      last 6 years in Institute "Seragnoli". All the patients were in 1st chronic
      phase, their median age was 37 years, the donors were HLA-identical (27/32) or 1
      Ag-mismatched (5/32) siblings. Big BuCy was the conditioning regimen employed for
      all and GVHD prophylaxis was based on CsA in 4 patients and Csa+MTX in 28
      patients; all patients received homogeneous pre and post-transplant supportive
      care, antimicrobial and antiviral prophylaxis. These patients were divided into 2
      groups according to the treatment before BMT: 16 received IFN from diagnosis to
      BMT (mean dose 6.9 MU/daily) for at least 6 mos (mean 23 mos, range 8-75) and 16
      received chemotherapy alone (hydroxyurea [HU]). RESULTS: Hematological recovery
      was comparable in the two groups: time to 0.5 x 10(9)/L PMN was 20.5 days (range
      11-32) in the IFN group and 20 days (range 10-32) in the HU group; time to 50 x
      10(9)/L platelets was 28 days (range 20-117) in the IFN group and 27 days (range
      20-112) in the HU group. The incidence of acute GVHD was not different in the two
      groups for any grade of the disease; in patients who survived more than 100 days,
      chronic GVHD occurred in the two groups with the same frequency. Seven patients
      died of transplant related mortality (TRM), 4 in the IFN group and 3 in the HU
      group. Hematological relapse was observed in only one case in the HU group; no
      cytogenetic relapse occurred. Disease free survivals at 7 years are 61% and 72%,
      respectively; the difference is not significant. INTERPRETATIONS AND CONCLUSIONS:
      Notwithstanding the low number of patients included in this study, the data
      reported here confirm that prior treatment with alpha-IFN does not adversely
      affect transplant outcome.

PMID- 9573678
TI  - Study of serum alanine-aminotransferase levels in blood donors in Spain.
AB  - BACKGROUND AND OBJECTIVE: Serum alanine-aminotransferase (ALT) is being used as a
      surrogate test for preventing post-transfusion viral hepatitis. However, ALT
      elevation is influenced by many factors. We have studied ALT levels in 1,036
      consecutive blood donors to determine their association with gender, obesity, and
      hepatitis virus infection markers. DESIGN AND METHODS: In each donation aspartate
      aminotransferase (AST), lactate dehydrogenase (LDH) and gamma-glutamyl
      transferase (gamma GT) activity were also determined and body mass index (BMI)
      was calculated. RESULTS: Five hundred seventy-nine men and 457 women donated
      blood; ALT activity was 25.3 +/- 14.5 IU/L (mean +/- SD) for men and 16.3 +/- 7.9
      IU/L for women (p < or = 0.0005). The upper normal value for men was 56 IU/L and
      34 IU/L for women. On applying this value to the study group 4.8% of the men and
      2% of the women had values greater than the cutoff. Among the men with increased
      ALT levels, 53.5% had a BMI > 27, 7.1% also had an increased level of GGT and
      7.1% had increased levels of AST and LDH. None of them were HBsAg nor anti-HCV
      positive. Among the women with increased ALT, 33.3% had BMI > 27, 33.3% had
      increased levels of LDH and AST, and 11.1% were anti-HCV positive (only 1 donor).
      INTERPRETATION AND CONCLUSIONS: It seems clear that different cutoff values
      should be considered for men and women. Factors such as obesity, may account for
      more than 50% of the cases with increased ALT values, indicating the low
      specificity of the test.

PMID- 9573679
TI  - Hereditary spherocytosis: from clinical to molecular defects.
AB  - Resistance and elastic deformability of red cells are due to a protein network
      (cytoskeleton) that laminates the lipid bilayer and to proteins that span the
      latter. All proteins are interconnected. Their structure as well as the structure
      of the corresponding genes are now well known. Hereditary spherocytosis (HS) is
      the most common hemolytic anemia due to a red cell membrane defect. It derives
      from alterations of the following genes: ANK1, EPB3, ELB42, SPTA1 and SPTB. This
      condition is clinically, biochemically and genetically heterogeneous. The
      osmotically fragile spherocytes are selectively trapped in the spleen and
      destroyed. Increased red blood cell destruction causes the three main clinical
      signs of HS: anemia, jaundice and splenomegaly. In this review we analyze the
      most recent advances concerning the molecular basis and the clinical course of
      HS. In particular, we examine the major individual proteins that constitute the
      skeleton, which are now known to play an essential role in the pathogenesis of
      HS. This paper also includes a review of the therapeutical approach to HS.
      Concerning the diagnosis we provide a flow chart from the clinical aspects to the
      molecular diagnosis.

PMID- 9573680
TI  - Diagnosis, classification, and cytogenetics of myelodysplastic syndromes.
AB  - BACKGROUND AND OBJECTIVE: The diagnosis of myelodysplastic syndromes (MDS) is
      essentially morphological and based on the presence of dysplastic features in the
      peripheral blood and bone marrow. The French-American-British (FAB) Cooperative
      Group proposed a classification based on easily obtainable laboratory
      information. In spite of some limitations, the FAB criteria have been useful for
      a long time. Currently, the recognition of other distinct morphological MDS
      subgroups such as hypocellular MDS and MDS with myelofibrosis, the increasing
      incidence of MDS in children as well as that of therapy-related MDS, and the
      finding of specific chromosomal alterations associated with different
      morphological features, reveal the insufficiency of this classification. The aim
      of the present review is to examine some new aspects of the diagnosis,
      classification, and cytogenetics of MDS. EVIDENCE AND INFORMATION SOURCES: The
      authors of this review have been actively working and contributing original
      papers on MDS for the last 15 years. They also organized or participated in the
      Fourth International Symposium on MDS (Barcelona, April 24-27, 1997). In
      addition, the present review critically examines relevant articles and abstracts
      published in journals covered by the Science Citation Index and Medline. STATE OF
      THE ART AND PERSPECTIVES: Most of investigators working on MDS tend to integrate
      morphology and cytogenetics in the diagnosis and classification of these
      disorders. FAB criteria remain useful particularly for patients with not
      available cytogenetic study. Refractory cytopenia with multilineage dysplasia
      should be considered as a new MDS subtype. Some authors propose considering all
      patients with more than 20% of blast cells in peripheral blood or bone marrow as
      having acute leukemia. Chronic myelomonocytic leukemia with myeloproliferative
      features may be included among chronic myeloproliferative disorders. MDS with
      myelofibrosis is recognized as a new MDS subtype. Therapy-related MDS (t-MDS)
      should be classified according to the involved agents. Finally, besides including
      chromosomal abnormalities in the diagnosis (e.g., RAEB with trisomy 8), several
      cytogenetic abnormalities such as deletion 5q and deletion 17q, associated to
      specific clinical-morphological features, should be of help to identify new MDS
      syndromes.

PMID- 9573681
TI  - The parallel between CD45 expression and extra-medullary evolution in aggressive
      myeloma with high serum lactate dehydrogenase.

PMID- 9573682
TI  - Simultaneous ischemic and hemorrhagic lesions of the brain detected by CT scan in
      a patient with thrombotic thrombocytopenic purpura.

PMID- 9573683
TI  - Fludarabine and cytosine-arabinoside for poor-risk acute myeloid leukemia.
AB  - Thirteen relapsed or refractory AML patients were treated with the FLA regimen. A
      complete remission was observed in 54% of cases but the median duration of
      remission was short (4 months). These results suggest that the FLA regimen is not
      able to induce a durable complete remission in the poor-risk AML patients.

PMID- 9573684
TI  - Therapy-related acute leukemia associated with involvement of 11q23 after high
      grade non-Hodgkin lymphoma.
AB  - Therapy-related acute myeloid leukemias with balanced translocations affecting
      the 11q23 chromosome region are one of the most serious complications of
      treatments with topoisomerase II inhibitor drugs as epipodophillotoxins and
      anthracyclines. 1,2-5 These cases are usually associated with short interval time
      from previous chemotherapies, absence of myeloid dysplastic phase,
      hyperleukocytosis and young age. We and others have recently identified and
      cloned the ALL1 gene at 11q23 band (also named MLL, HRX. Hrxt) which is
      consistently altered in t-AML following therapies with topo II targeting drugs.
      However, there are few reports of cases of t-AML, clinically and biologically
      similar to the subtype of leukemias secondary to exposure to topo II inhibitors
      drugs but without the involvement of the ALL1 gene. These observations suggest
      that genes other than ALL1 which are etiopathogenetically relevant for
      hematological neoplasias are located in this cytogenetic region.

PMID- 9573685
TI  - Achromobacter xylosoxidans bacteremia in patients with hematologic malignancies.
AB  - We report nine cases of Achromobacter xylosoxidans bacteremia diagnosed in
      patients with hematologic malignancies. There was not an obvious epidemiologic
      link between cases and the organism was not isolated from any source. Outcome was
      cure in all nine cases. In our experience, catheter removal is generally required
      for eradication of A. xylosoxidans.

PMID- 9573686
TI  - Primary orbital lymphoma: contralateral relapse after six years in complete
      remission.

PMID- 9573687
TI  - Transfusion-associated red eye syndrome.

PMID- 9573688
TI  - 'I think I can ... I thought I could'.

PMID- 9573689
TI  - Managed care and medicine.

PMID- 9573690
TI  - That other 80 percent.

PMID- 9573691
TI  - Periodontal and cardiovascular diseases.

PMID- 9573692
TI  - Care questioned.

PMID- 9573693
TI  - Access to dental care in the United States.
AB  - The authors analyzed data from the 1994 National Access to Care Survey and
      estimated the extent of dental care wants in the U.S. population and in various
      population subgroups. The authors found that 8.5 percent of the population
      wanted, but did not readily obtain, dental care in 1994. The prevalence of unmet
      dental care wants varied by demographic and socioeconomic characteristics, and
      income and health insurance status. Findings suggest that financial barriers to
      access are significant in explaining the prevalence of wanted dental care.

PMID- 9573695
TI  - Root-surface caries formation: effect of in vitro APF treatment.
AB  - To determine the effect of one and four-minute acidulated phosphate fluoride, or
      APF (Oral-B Minute Gel, Oral-B Laboratories) treatments on artificial caries
      development in root surfaces, an in vitro study was conducted. The authors
      created a window of exposed root surface on extracted teeth by applying acid
      resistant varnish to the remaining surface. APF treatment was administered and
      followed by a 24-hour deionized-distilled water rinse. A window of sound root
      surface that had been protected from the APF treatment was exposed and served as
      a control. Acidified gel was then applied to the exposed root surfaces to create
      the artificial caries. The authors found that APF treatment significantly
      enhanced resistance to demineralization of root surfaces from an in vitro
      acidogenic challenge. However, there was little difference in effectiveness
      between the one- and four-minute APF treatment times.

PMID- 9573694
TI  - Predicting chronicity in acute temporomandibular joint disorders using the
      research diagnostic criteria.
AB  - The authors describe a prospective study designed to examine the clinical utility
      of the Research Diagnostic Criteria for Temporomandibular Disorders, or RDC/TMD,
      in evaluating physical and psychological differences between patients with acute
      TMD that does not become chronic and patients with chronic TMD. A total of 153
      patients with acute TMD participated in the study; the researchers deemed the
      condition of 87 of these patients to be chronic after a six-month follow-up
      period, and that of 66 patients to be nonchronic. Using a multiple logistic
      regression model, the authors found that a number of physical and psychological
      variables differed significantly between the two groups. These results highlight
      the importance of the physical-psychosocial interface that affects the
      development of chronic TMD.

PMID- 9573696
TI  - Dentin-bonded all-ceramic crowns: current status.
AB  - Dentin-bonded all-ceramic crowns employ contemporary techniques to lute the crown
      to the tooth using a resin luting material and dentin-bonding system. The
      advantages of these crowns are that they provide good esthetics and fracture
      resistance and can be used in cases of substantial tooth loss. Their principal
      disadvantages are that the luting procedure is more time-consuming and that these
      crowns should not be used where margins are subgingival. Dentin-bonded all
      ceramic crowns may be a useful addition to the dentist's armamentarium, but long
      term clinical studies are needed to fully assess their performance.

PMID- 9573697
TI  - Interpreting vital sign profiles for maximizing patient safety during dental
      visits.
AB  - Concerns about local anesthetics and dental treatment stress are still prevalent
      in today's medical and dental communities. The authors conducted 24-hour
      monitoring of heart rate and blood pressure for 23 patients undergoing two root
      planing procedures and a single periodontal surgical procedure. Chronobiologic
      analysis of circadian blood pressure and heart rate rhythms revealed that neither
      epinephrine vasoconstrictor in anesthetics nor increased invasiveness of the
      procedure resulted in statistically significant deviations from regular,
      individualized blood pressure rhythms. For surgical appointments, time of day had
      the greatest effect on cardiovascular variables, with the greatest elevations in
      blood pressure seen for surgery at 8 a.m. and the largest blood pressure
      decreases seen for surgery at 2 p.m.

PMID- 9573698
TI  - A case report. Treating localized refractory idiopathic gingivitis with
      Superoxol.
AB  - The authors describe a case of localized refractory idiopathic gingivitis in a 29
      year-old patient that was successfully treated with hydrogen peroxide (Superoxol,
      Sultan Chemists, Inc.). The gingivitis was refractory to previous oral hygiene
      measures and was persistent in the face of meticulous oral hygiene. This case
      illustrates a successful treatment measure for an uncommon clinical challenge.

PMID- 9573699
TI  - Toward increased sensitivity and specificity in the treatment of neoplastic
      diseases.

PMID- 9573700
TI  - Air abrasion tooth cutting: state of the art 1998.

PMID- 9573702
TI  - A simple technique for operatory placement of overdenture attachments.

PMID- 9573701
TI  - Chemical hemostasis for prosthetic recementations.

PMID- 9573703
TI  - What process is due?

PMID- 9573704
TI  - Dental amalgam: update on safety concerns. ADA council on Scientific Affairs.
AB  - This report of the Council on Scientific Affairs reviews and discusses recent
      studies concerning the safety of dental amalgam, with an emphasis on studies that
      have been published since the 1993 review of dental amalgam by the U.S. Public
      Health Service Committee to Coordinate Environmental Health and Related Programs.
      The Council concludes that, based on currently available scientific information,
      amalgam continues to be a safe and effective restorative material.

PMID- 9573705
TI  - Monitoring approved research protocols--a question of balance. National Health
      and Medical Research Council.
AB  - This paper seeks to explore the various problems associated with monitoring
      research protocols that have received ethical approval by an Institutional Ethics
      Committee (IEC). It begins with an outline of the current Australian Guidelines
      on the Monitoring of Research; noting the primary importance of an effective
      monitoring mechanism being to ensure that the conduct of research involving human
      beings does not jeopardise the rights and interests of research subjects. The
      paper provides an outline of the current practice adopted by institutional ethics
      committees in Australia in fulfilling their obligations to monitor approved
      research protocols. The paper gives further consideration to some of the problems
      associated with monitoring, as well as noting the problem concerning the lack of
      sufficient resources for IECs, impacting not only on their ability to fulfill
      their monitoring obligations but equally on their capacity to perform their
      general tasks. Finally, a number of options are proposed, and some attention is
      given to the resource implication for IECs, with a range of options being
      canvassed to ensure that IECs are better resourced and in a position to
      efficiently manage their workload.

PMID- 9573706
TI  - Parental right to determine whether to use aggressive treatment for an early
      gestational age infant: the Messenger case.
AB  - Manslaughter charges were brought against Dr. Gregory Messenger, a Michigan (USA)
      dermatologist, for removing his extremely premature infant son from a ventilator
      in the neonatal intensive care unit. Prior to delivery the neonatologist had told
      the parents that at the infant's age there was a 50-70% mortality and that if the
      child did survive there was a 20-40% chance of severe intraventricular
      hemorrhage. The newborn infant had been placed on mechanical life support despite
      the explicit instructions of the parents that they did not want aggressive or
      resuscitative measures used on their 780g., infant born at 25 weeks gestational
      age. The defendant argued that given the child's precarious medical status, it
      was the right of the parents to determine whether or not to institute aggressive
      medical interventions. The jury acquitted the father of all charges.

PMID- 9573707
TI  - Human research beyond the medical model: legal and ethical issues.
AB  - Advances in medical health depend on non-medical, as well as medical research.
      When research involves human participants, it raises legal and ethical concerns
      that have come to be approached by reference to codes of research ethics. Many of
      these are centered on physician-patient relationships and the pursuit of medical
      science. This article considers a number of issues that arise from research that
      follows non-medical models of research, and applications of rules of ethical
      medical research outside physician-patient settings. In particular, it addresses
      health research in the social sciences, the exclusion of women as participants in
      medical research, studies that depend on incomplete disclosure of information to
      prospective participants and their deception, and public health research based on
      groups and communities rather than participants as individuals.

PMID- 9573708
TI  - The cautious acceptance of informed consent in Japan.
AB  - The Japanese medical profession has come under increasingly intense scrutiny from
      the media and the public. Calls for recasting the traditional paternalistic
      doctor-patient relationship have become sufficiently pervasive that the medical
      profession itself has accepted the need to incorporate "infomudo konsento" (the
      English term is commonly used, for lack of a satisfactory phrase in Japanese)
      into medical practice. The medical establishment is attempting to accomplish this
      endeavor in a tamed and "Japanized" form which preserves professional autonomy.
      This paper attempts to illuminate the distinctive tenacity of Japanese medical
      paternalism. First, the paper presents a descriptive model of cultural
      paternalism characteristic of traditional Japanese medicine, taking as examples
      four specific practices: concealing from patients the diagnosis of cancer;
      withholding from patients information about drugs; requiring patients to sign
      waivers of rights; and refusing patients access to their own medical records.
      Second, the paper describes how the economic structure of Japanese health care
      reinforces these cultural proclivities toward paternalism. Third, the paper
      explores the paradox of the legal system's treatment of informed consent issues.
      The paper then addresses the sources of a gradual transformation in attitudes
      concerning informed consent. Emphasis is given to transformative forces peculiar
      to Japan: the controversy over brain death and organ transplantation, in which
      the rhetoric of informed consent has come to be used by all parties as a weapon
      of convenience and the enforcement (amidst publicity surrounding deaths from
      experimental drugs and international pressures for drug exports to meet accepted
      standards of biomedical ethics) of rules requiring informed consent in clinical
      trials of investigational drugs. The paper finally assesses the impact of the
      1995 report of the prestigious Study Commission on Informed Consent.

PMID- 9573709
TI  - Insight and competence to consent to psychiatric hospitalization.
AB  - Informed consent and insight are among the most important issues in medical
      treatment, especially for psychiatric patients. In this study, we examined the
      competence to consent to psychiatric hospitalization of 113 psychiatric patients
      who were voluntarily admitted to a mental hospital in various psychotic states
      and compared it with their insight. We found a significant correlation between
      the patients' competence and insight into their illnesses. There is a discussion
      of the problematic issues of informed consent, competence and psychosis and the
      importance of insight in the context of mental illness.

PMID- 9573710
TI  - Health nurses: attitudes towards treating AIDS patients.
AB  - Many nurses working in hospitals, especially in the wards, as well as nurses in
      community clinics have been involved in treating AIDS sufferers. In spite of
      clear and widespread information available to professionals, strong apprehensions
      still exist as to the contagious nature of the disease. A survey was carried out
      in order to assess the attitudes of nurses in this regard. Participants were
      drawn from the nursing profession, all were Registered Nurses (R.N.) The survey
      was carried out in the centre of the country and involved 137 participants, 69 of
      whom were hospital nurses and 68 community health nurses. Their average age was
      43 years with an average professional experience of 10 years. A questionnaire was
      issued containing 24 closed questions, based on professional knowledge, clinical
      experience, professional literature, and attitudes towards treatment, as well as
      obligations involving information to family members and other institutions and
      commitment to HIV patients.

PMID- 9573711
TI  - Sexual abuse within the marital relationship.
AB  - The authors aim to characterise sexual abuse within the marital relationship.
      They analyzed the reports of the clinical examinations performed at the Institute
      of Legal Medicine of Oporto on victims of sexual abuse from January 1990 until
      December 1994. They also randomly interviewed victims of physical abuse at the
      Institute to determine if sexual abuse was performed by their partners. This
      study shows that complaints are rarely reported by victims of sexual abuse in
      marital relationships, and in all the cases studied where sexual abuse was
      verified it was accompanied by other forms of abuse.

PMID- 9573712
TI  - Psychotherapy of paraphilic sex offenders.
AB  - The author provides a brief review of the current state of therapy for sex
      offenders in different countries and emphasizes psychotherapeutical models of
      treatment. He describes the course, complications and objectives of this therapy.
      The Czech model of specialized comprehensive treatments of paraphilic sex
      offenders is described. After twenty years of specialized approach in the therapy
      of sex offenders in the Czech Republic, the re-offense rate of 953 treated
      patients was 17.1%.

PMID- 9573713
TI  - Epilepsy and the law.
AB  - Epilepsy, and the treatment thereof, has effects on many aspects of life, with
      far-reaching implications for the patient, his family and the community. Epilepsy
      causes a great deal of social difficulties and restrictions due to the associated
      stigma and prejudice. It is not a rare condition and is associated with many
      other conditions, such as schizophrenia, mental retardation, autism, and terminal
      Alzheimer's disease. Other associated disorders may include cognitive
      difficulties, personality disturbances or psychoses of various types and
      durations. Only by the 1850's was epilepsy defined as a "neurological" disease.

PMID- 9573714
TI  - "Baby oh baby"--advances in assisted reproductive technology.
AB  - It is estimated that one couple in six in the United States has to deal with
      issues of infertility. It is assumed that worldwide rates are comparable. In 35%
      of cases, the infertility is caused by female reproductive problems, in 35% by
      male reproductive problems, in 15% by multiple factors and in 15% the cause is
      unknown. Medical and scientific advances in Assisted Reproductive Technology
      (ART) have created 12 different pregnancy producing options for infertile
      couples. An ART infant could have as many as five parents (i.e. a donor father, a
      donor mother, a surrogate or gestational mother, and the couple actually rearing
      the child). These technical, medical, and moral complexities have resulted in a
      nightmare of accompanying legal complexities: anonymous donors versus those with
      identification disclosed, parental rights, grandparental rights, the rights of
      siblings and of the extended families; sperm, ovum and embryo "ownership",
      custody, visitation and inheritance rights and multiple other issues challenge a
      system of laws that evolves far slower than the technological realities to which
      it applies. This presentation will describe Assisted Reproductive Technology
      advances and the legal implications inherent in them. Case histories will be
      discussed.

PMID- 9573715
TI  - A medico-legal evaluation of the use of assisted reproductive technologies in
      Turkey.
AB  - In Turkey, as possibly in the case of several or even many other countries,
      infertility is generally regarded as a negative phenomenon in women. Assisted
      Reproductive Technologies (ARTs), which provide certain childless couples with
      the possibility of having a baby, are being applied more and more frequently in
      this country, apparently as has been the case in the world at large. From a
      medicolegal point of view, the related applications in Turkey can only be
      realized in the case of married couples. Other forms of application in this area,
      on the other hand, such as sperm banks or surrogate motherhood, are not allowed
      legally. A text which was called "Guidelines Regarding the Centers of In Vitro
      Fertilization and Embryo Transfer" was prepared in 1987 by the Ministry of
      Health. The aim of these Guidelines is to find solutions to the medico-legal
      problems created by the application of ARTs in this country.

PMID- 9573716
TI  - Gamete donation from couple to couple in the new French law.
AB  - In practice, the partners or spouses of gamete donors are frequently asked
      permission for the donation. The new French law on bioethics of 29 July 1994
      requires that: a) the donor should be one of a couple that has already procreated
      and b) the written consent of the partner or spouse is obtained. These conditions
      lead not only to several practical problems in the organisation of donor
      insemination but also reject a large part of the potential donor population. The
      two basic qualities demanded of the donors, e.g., paternity and stable
      relationship, are analyzed. It is proposed that only fatherhood should serve as
      an exclusionary criterion for sperm donation. The donor need not be a part of a
      couple at the moment of the donation but if he has a partner at that time her
      opinion should be heard.

PMID- 9573717
TI  - Euthanasia in England: courts, committees and consistency.
AB  - Part I of this paper considers three competing ethical approaches to the
      valuation of human life: "Vitalism', 'Inviolability', and 'Worth'. Part II argues
      that, largely as a result of the case of Airedale NHS Trust v Bland, English law
      relating to 'euthanasia' (the intentional shortening of a patient's life, by act
      or omission, as part of his/her medical care) is in a morally and intellectually
      inconsistent state, incorporating Inviolability by prohibiting doctors from
      intentionally killing patients by an act but adopting Worth by permitting them
      intentionally to kill certain patients by omission. Part III maintains that the
      recent Report of the House of Lords Select Committee on Medical Ethics missed an
      opportunity to recommend the resolution of this inconsistency.

PMID- 9573718
TI  - Dealing with road rage.

PMID- 9573719
TI  - Religious connectedness among urban African American families who have a child
      with disabilities.
AB  - The role of religion and its relation to adjustment for 52 African American
      caregivers who had a child with mental retardation was examined. Comparative
      studies of cultural/ethnic contexts of families with a child who has disabilities
      often cite religion as a salient factor in family adjustment. This finding was
      expanded upon through (a) a focus on the African American population, (b) the
      relation of adjustment to religious experiences considered relevant to most
      African American families, and (c) documentation of the validity and reliability
      of the participants' responses to the Religious Connectedness Questionnaire.
      Religion in personal and family life and church support were related to positive
      outcomes in adjustment. Analysis of open-ended responses co-validated the
      quantitative outcomes.

PMID- 9573720
TI  - Whose quality of life is it anyway? Some problems with the emerging quality of
      life consensus.
AB  - Two critiques of the emerging consensus in the conceptualization and measurement
      of quality of life were presented. The first suggests that there are insuperable
      problems in assessing subjective indicators of quality of life and that this
      aspect of the quality of life approach should be abandoned. The second critique
      is that the quality of life approach, which claims to liberate people from a
      medical model, may paradoxically serve to extend the license of services to exert
      control over all facets of a person's life. In this view, the quality of life
      approach should be abandoned altogether. The solutions that follow from these two
      critiques were critically discussed with the aim of provoking a debate around the
      quality of life approach.

PMID- 9573721
TI  - Promoting long-term relationships between individuals with mental retardation and
      people in their community: an agency self-evaluation.
AB  - A descriptive analysis was conducted of data from survey instruments completed by
      25 trained volunteers serving for more than one year as companions to people with
      mental retardation. Factors such as a strong orientation process, adequate
      support from staff, appropriate matching with the people with mental retardation,
      positive characteristics of the people with disabilities, and a high perceived
      degree of reciprocity were characteristic of these stable relationships.
      Volunteers and their partners participated in a variety of recreational
      activities together. Although they encountered various logistical barriers to the
      relationships, respondents reported that these barriers did not impede the
      relationships.

PMID- 9573722
TI  - Students' expectations of the future: hopelessness as a barrier to self
      determination.
AB  - The development of self-determination depends on the emergence of positive
      beliefs about oneself and one's future. Research has suggested that these
      positive perceptions are the outcome of a process of learning and using problem
      solving skills and the achievement of perceived or actual control, referred to as
      learned hopefulness. Expectations for the future (e.g., hopefulness/hopelessness)
      of students with mental retardation, learning disabilities, or students without
      disabilities were examined. Students with mental retardation were significantly
      less hopeful than were their peers with learning disabilities or without
      disabilities. Implications from these findings for the development of self
      determination were discussed.

PMID- 9573723
TI  - Attitudes on inclusion of a player with disabilities in a regular softball
      league.
AB  - Although attitudes of sports participants relate significantly to the successful
      inclusion of individuals with disabilities in regular sport programs, there has
      been no published research on attitudes toward inclusion or rule modifications.
      We examined attitudes of girls without disabilities, their parents, and their
      coaches towards inclusion of a child with disabilities in a regular girls' fast
      pitch softball league. They completed the Attitudes Towards Integrated Sports
      Inventory prior to the season. Results suggest that players and parents had a
      favorable attitude towards inclusion and towards modifying the game rules to
      enable this player to have a safe, successful experience. Coaches were undecided
      about inclusion and rule modifications.

PMID- 9573724
TI  - Self-reported fears in Hispanic youth with mental retardation: a preliminary
      study.
AB  - There is a paucity of research on the frequency, intensity, and content of fears
      experienced by Hispanic (or Latino) American youth with mental retardation. We
      assessed fears experienced by 48 Hispanic youth with mental retardation (ages 10
      to 21 years) using the Fear Survey for Children With and Without Mental
      Retardation. Although differences were found in the content of fears across age
      and gender groups, the number and intensity of fears did not differ. Promising
      evidence of the validity of this survey instrument was attained by its
      significant correlations with the Revised Children's Manifest Anxiety Scale.
      Implications for future research were discussed.

PMID- 9573725
TI  - On the outside looking in: attending to waiting lists in systems of services for
      people with developmental disabilities.

PMID- 9573726
TI  - Hope, opportunity, and possibility: supporting people with developmental
      disabilities at the end of the 20th century.

PMID- 9573727
TI  - Decreases continue in out-of-home residential placements of children and youth
      with mental retardation.

PMID- 9573728
TI  - A report not to be taken with a grain of salt.

PMID- 9573729
TI  - Ex parte disclosure of patient medical information to third parties involved in
      litigation with the patient.

PMID- 9573730
TI  - Breast cancer incidence and mortality trends in Missouri.
AB  - Among women in Missouri as in the United States (U.S.), breast cancer is the
      leading site of new cancer cases and the second leading cause of cancer deaths.
      This study examined patterns of breast cancer incidence and mortality among
      Missouri women. Age-adjusted Missouri incidence (1985-1992) and mortality (1985
      1994) data were compared with Surveillance, Epidemiology, and End Results (SEER)
      data (1985-1992) by race and diagnosis year. Missouri Cancer Registry (MCR) data
      indicate that there have been no significant changes in breast cancer incidence
      and mortality rates through the time periods. Incidence rates for Missouri
      females (White, African-American and All) are significantly lower than SEER rates
      for all age groups, with greater differences in all races among women over 65.
      Incidence rates for African-Americans are significantly lower than for whites.
      However, Missouri mortality rates for African-Americans fluctuate over the
      period, but are consistently higher than for whites. In addition, African
      Americans over age 65 have higher mortality rates in Missouri than in the U.S.

PMID- 9573731
TI  - Diagnostic deception experience with melanoma.

PMID- 9573732
TI  - Emergency medicine quiz #5. Delayed labial artery bleeding.

PMID- 9573733
TI  - Thrombolytic therapy in Missouri hospital emergency departments: compliance with
      the National Heart Attack Alert Program guidelines.
AB  - A self-administered questionnaire concerning the current practice of thrombolytic
      administration, and the use of National Heart Attack Alert Program (NHAAP)
      guidelines was mailed to the medical directors of Missouri acute care emergency
      departments (EDs). Responses from 75% of the EDs surveyed were received. There
      were standing orders to perform an electrocardiogram at 92% of the EDs surveyed.
      Thrombolytics were stocked in 80% of EDs and thrombolytics were administered in
      the ED rather than the ICU or CCU at 98%. The emergency physician (EP) was
      authorized to make thrombolytic treatment decisions at 87% of the institutions;
      however, in 24% of the hospitals EPs were required to contact another physician
      prior to giving thrombolytics. An Acute Myocardial Infarction (AMI) Continuous
      Quality Improvement (CQI) program was in place at 67%, and 44% of the
      institutions had an interdepartmental AMI protocol. Less than half of the EDs
      reported a door-to-drug time of less than 30 minutes. The primary delay in
      starting thrombolytic therapy was identified as decision-making on the part of
      the emergency physician and/or consultants. Missouri EDs report that they
      generally follow the NHAAP guidelines for rapid identification and treatment of
      AMI, but, there were still significant delays reported in the administration of
      thrombolytics.

PMID- 9573734
TI  - Births, marriages, divorces, and deaths for August 1997.

PMID- 9573735
TI  - Once-daily aminoglycosides: practical guidelines.
AB  - There is ample evidence that once-daily dosing of aminoglycosides is preferable
      to the conventional regimens during the treatment of serious infections.
      Experimental and clinical studies also provide evidence that this regimen can be
      safely used in children, neutropenic patients and endocarditis. The use of once
      daily tobramycin in cystic fibrosis merits further study, as the pharmacokinetics
      of the aminoglycosides are altered in these patients. The dose-adjustment
      strategy in patients with renal failure is still controversial, but reducing the
      daily dose whilst maintaining the q24-h interval has been demonstrated to be
      safe. Although the value of serum level monitoring in ensuring efficacy and
      avoiding toxicity has been overestimated in the past, especially in patients with
      renal failure, an undesirable accumulation of the aminoglycosides can occur. The
      best way to detect accumulation remains to be defined.

PMID- 9573736
TI  - Four-day lansoprazole-quadruple therapy in the routine treatment of Helicobacter
      pylori infection.
AB  - BACKGROUND: Ulcer patients need to be treated for Helicobacter pylori infection.
      Seven days of quadruple therapy achieves the highest cure rates. In this study a
      4-day quadruple regimen of lansoprazole, bismuth, tetracycline and metronidazole
      is investigated. METHODS: In an open study 66 consecutive infected patients with
      ulcer disease or non-ulcer dyspepsia were treated with 4-day quadruple therapy
      after 3 days of lansoprazole pretreatment. H. pylori status was determined before
      and at least 6 weeks after therapy by endoscopy with antral and corpus biopsies
      for rapid urease test, histology and culture. RESULTS: Sixty-four patients took
      the medication and complete compliance was achieved in 60 (94%). Tolerability was
      excellent and there were no drop-outs due to side-effects. Overall 55 out of 64
      (86%, 95% CI 77.4-94.4%) were cured, including 41/44 with a metronidazole
      sensitive strain 5/8 with a resistant strain. CONCLUSIONS: Four-day quadruple
      therapy is well tolerated and very effective especially in metronidazole
      sensitive strains. This study lends further support for the use of one-week
      quadruple therapy as empiric first line anti-Helicobacter therapy for Dutch ulcer
      patients. If patients suffer from side-effects during this therapy stopping
      treatment at day 4 can be advised.

PMID- 9573737
TI  - Streptococcus pneumoniae, an emerging pathogen in mycotic aneurysms?
AB  - Two patients are described with a mycotic aneurysm caused by streptococcus
      pneumoniae infection. The patients presented with back pain and fever, and had an
      antecedent history of lower respiratory tract infection; neither of them were
      suffering from endocarditis. Mycotic aneurysms are a rare disorder with, over the
      years, a changing spectrum of presentation, localisation and bacterial aetiology.
      S. pneumoniae infection has only very rarely been reported as a cause of mycotic
      aneurysms. Since 1986, 14 patients with a mycotic aneurysm were treated at the
      Leiden University Hospital. Of these patients, 5 had mycotic aneurysms caused by
      S. pneumoniae infection. The mortality in these patients was high. In this
      communication, we would like to draw attention to S. pneumoniae infections as an
      emerging cause of mycotic aneurysms.

PMID- 9573738
TI  - Acquired angio-oedema caused by IgA paraprotein.
AB  - The syndrome of acquired angio-oedema is characterized by late onset of recurrent
      bouts of angio-oedema or abdominal pain and may be caused by an acquired
      deficiency of C1-inhibitor (C1-INH), the inhibitor of the first component of
      complement. Acquired C1-INH deficiency has been described in approximately 50
      patients and is strongly associated with malignant B-cell proliferations. We
      describe a patient with an 8-year history of recurrent abdominal symptoms and
      angio-oedema with acquired C1-INH deficiency, caused by the presence of IgA-kappa
      antibodies that inactivate C1-INH. Analysis of the bone marrow revealed an IgA
      kappa monoclonal population of plasma cells, without evidence of overt myeloma.
      Angio-oedema caused by an autoantibody of the IgA isotype is extremely rare and
      has never been described in a Dutch patient. Recognition of angio-oedema, both
      hereditary and acquired, is important because of the therapeutic consequences, as
      will be discussed.

PMID- 9573739
TI  - Clozapine-induced agranulocytosis: a case report. Immunopathophysiological
      considerations.
AB  - A 46-year-old woman is described with a clozapine-induced agranulocytosis. She
      was treated with a broad-spectrum antibiotic and supportive care was provided
      with granulocyte colony-stimulating factor (G-CSF). Immune-mediated mechanisms of
      clozapine-induced agranulocytosis and the role of haematopoietic growth factors
      are discussed.

PMID- 9573740
TI  - Haematological recovery after high-dose consolidation chemotherapy with
      peripheral blood progenitor cell rescue: the effects of the mobilization regimen
      and post-transplant growth factors.
AB  - PURPOSE: Peripheral blood progenitor cells (PBPC), mobilized by chemotherapy,
      growth factors (GF) or the combination of these modalities are currently used in
      most autologous transplants settings. Patient selection factors and infused cell
      numbers have been related to the rate of haematological recovery after transplant
      (p-Tx). The effect of the mobilization regimen on haematological recovery has
      rarely been reported and is addressed herein. The value of p-Tx GF use is also
      evaluated. METHODS: A literature review identified studies reporting both
      mobilization results and haematological recovery (time to ANC > 0.5 or 1.0 x
      10(9)/1 and PLT > 20 or 50 x 10(9)/1). The studies are listed in tables showing
      the mobilization regimen, disease, infused CD34+ cell and CFU-GM dose, p-TX GF
      use and haematological recovery. The ranges of recovery times for each transplant
      setting are summarized in a figure in addition to the ranges of recovery times
      using GF after autologous bone marrow transplants in controlled studies. RESULTS:
      Transplantation of cells mobilized by G-CSF results in faster haematological
      recovery than transplantation of cells mobilized by GM-CSF. This difference
      disappears when chemotherapy is included in the mobilization regimen. GF have
      minimal effect on haematological recovery after transplantation of PBPC mobilized
      by chemotherapy plus GF and some effect on neutrophil recovery after transplants
      of PBPC mobilized by GF only. CONCLUSIONS: Recovery after PBPC transplantation
      depends on the mobilization method and is best predictable when mobilization
      occurs with chemotherapy plus GF. In this situation, the value of post-transplant
      growth factors is questionable. Careful choice of the mobilization method,
      including optimal timing of leucapheresis and patient selection factors,
      determine the leucapheresis yield and thus the rate of haematological recovery.

PMID- 9573741
TI  - The management of psoriasis.
AB  - A spectrum of treatments is available for patients with psoriasis. It is of
      utmost importance to individualize the selection of treatment for the individual
      patient at the very moment of consultation. The manifestation of psoriasis, the
      extent of the lesions and the subjective discomfort of psoriasis are important
      factors which denominate the selection of treatment. The most important topical
      treatments are calcipotriol, dithranol, tar and corticosteroids. If topical
      treatments are unsuccessful, phototherapy with UVB, photochemotherapy (PUVA),
      methotrexate, cyclosporin and acitretin are the most important therapeutical
      options. The possibilities and limitations of these treatments will be presented
      in this review. In particular, the question will be addressed to what extent
      treatments of psoriasis may have systemic complications.

PMID- 9573742
TI  - Duodenal diverticula: a wide spectrum of complications.

PMID- 9573743
TI  - Effects of inhaled corticosteroids on bone.

PMID- 9573744
TI  - [XLIX Annual meeting of the Spanish Neurological Society. Barcelona, Spain, 10-13
      December 1997. Abstracts].

PMID- 9573745
TI  - Ultrasonic image analysis of the arterial wall in atherosclerosis.
AB  - BACKGROUND: Atherosclerotic carotid artery plaques can be classified on the basis
      of their ultrasound appearance according to the pattern of echolucency and
      echogenicity. The most commonly used classification is the one described by Gray
      Weale who defined 4 plaque types. METHODS: The images of the carotid and femoral
      arteries of 9 healthy volunteers and 21 non-insulin dependent diabetic patients
      were analysed. In this study 16 atherosclerotic carotid artery plaques were
      imaged by B-mode high resolution ultrasonography and then subjected to analysis
      of the digitised images. RESULTS: The results show that the plaques could be
      separated into 3 groups according to their echogenic properties. Gray-Weale
      plaques types 2 and 3 could not be distinguished and it is proposed that these
      should be classified as a single group. CONCLUSIONS: An increased echogenicity in
      the intima-media complex of non-insulin dependent diabetics as well as a
      relationship with risk factors for the development of cardiovascular disease and
      with the ultrasound score could not be determined in this study.

PMID- 9573746
TI  - Health-related physical function and quality of well-being prior to and following
      cardiomyoplasty. A preliminary report.
AB  - OBJECTIVE: The purpose of this study was to obtain preliminary data regarding the
      effects of cardiomyoplasty on health-related physical function and quality of
      well-being. EXPERIMENTAL DESIGN: Quasi-experimental with repeated measures.
      Patients were interviewed prior to surgery, with post-surgical follow-up
      interviews at 6 weeks, 6 months, and 12 months. SETTING: Interviews were usually
      conducted by telephone with patients who were at home at the time of data
      collection. PATIENTS OR PARTICIPANTS: Four patients receiving cardiomyoplasty at
      Allegheny General Hospital in Pittsburgh, Pennsylvania. INTERVENTIONS: Patients
      received cardiomyoplasty between November 1992 and April 1993. Cardiomyoplasty
      using the right latissimus dorsi muscle was performed on the first patient. A
      left muscle-wrap was performed on the subsequent three patients. MEASURES: Self
      reported function and well-being were measured using the Sickness Impact Profile
      (SIP), the Quality of Well-Being Scale (QWB), and the Medical Outcome Study 36
      Item Short-Form Health Survey (SF-36). RESULTS: Patient responses on the SF-36
      demonstrated general improvement in cardiomyoplasty survivors. Results on the QWB
      and SIP are mixed. CONCLUSIONS: Due to the small, incomplete sample and lack of
      any comparison group, extreme caution must be used in drawing any clinical
      conclusions from this preliminary data. Future randomized clinical trials of
      cardiomyoplasty need to include quality of life and health-related physical
      function as dependent variables. Further psychometric study is necessary which
      compares the usefulness of these various methods for assessing the value of
      outcomes for patients with end-stage heart disease.

PMID- 9573747
TI  - GH response to GHRH combined with pyridostigmine or arginine in different
      conditions of low somatotrope secretion in adulthood: obesity and Cushing's
      syndrome in comparison with hypopituitarism.
AB  - BACKGROUND: Diagnosing GH deficiency in adults is difficult due to the age
      related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH
      replacement is allowed for patients with GH peak to provocative stimuli < 3
      micrograms/L. Somatotrope insufficiency is present in hypopituitarism but also in
      obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is
      difficult due to variations of GH and IGF-I levels as function of age and
      nutrition status. METHODS: We aimed to verify the GH response to GHRH (1
      microgram/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine
      (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women
      (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS).
      RESULTS: IGF-l levels in GHD were lower than those in OB (p < 0.01) and in CS (p
      < 0.01) which, in turn, were lower to those in NS (p < 0.02). In NS, the GH peak
      responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak
      was 16.5 micrograms/L. GHD had GH responses similar, lower than those in NS (p <
      0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks <
      3 micrograms/L; conventionally, below this limit severe GH deficiency is shown
      and rhGH replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH +
      ARG were similar, lower (p < 0.01) and higher (p < 0.01) than those in NS and
      GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but
      nobody < 3 micrograms/L. In CS the GH response to GHRH + PD was lower than that
      to GHRH + ARG (p < 0.01); both these responses were lower than those in NS (p <
      0.01) and even in OB (p < 0.01) but higher than those in GHD (p < 0.01). All and
      7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH,
      respectively while 6/8 showed GH peak < 3 micrograms/L after PD + GHRH but only 1
      after ARG + GHRH. CONCLUSIONS: Present data demonstrate that the maximal
      somatotrope secretory capacity is reduced in OB and even more in CS. From a
      diagnostic point of view, PD + GHRH and ARG + GHRH tests distinguish OB from
      severe GHD. As hypercortisolism impairs the activity of cholinesterase
      inhibitors, only ARG + GHRH, but not PD + GHRH is a reliable test to explore the
      maximal somatotrope secretory capacity in CS. Notably, even with the ARG + GHRH
      test, in CS the maximal somatotrope secretory capacity is sometimes so reduced as
      to overlap with that of severe GHD.

PMID- 9573748
TI  - Effects of hormone replacement therapy on glucose metabolism.
AB  - OBJECTIVE: To evaluate the relationship between hormone replacement therapy and
      glucose metabolism, and the possible role played by the administration route.
      DESIGN: Prospective randomized study. MATERIALS AND METHODS: Eighty-four patients
      in either surgical or spontaneous menopause were randomly allocated into four
      groups: 15 patients in surgical menopause were treated with estrogens alone
      administered transdermically (17 beta-estradiol, 50 micrograms/day); 15 patients
      in surgical menopause were treated with oral conjugated equine estrogens (0.625
      mg/day); 18 patients in spontaneous menopause were treated with transdermic
      estrogens plus oral progestagen (17 beta-estradiol 50 micrograms/day, acetate
      medroxyprogestogen 10 mg/day for 12 days per month); 16 patients in spontaneous
      menopause were treated with oral conjugated equine estrogens (0.625 mg/day) plus
      oral progestagen (10 mg/day for 12 days per month). Twenty patients not given any
      medication represented the control group. Before starting the trial and after six
      months of therapy, glucose and insulin levels before and after an oral glucose
      loading test were evaluated. Data analysis was performed by means of Student's
      "t"-test, ANOVA was used to compare mean levels between the groups. Significance
      was set at p < 0.005. RESULTS: Dosages made after 6 months of therapy showed
      comparable basal glucose levels in all the studied group, while basal insuline
      levels in patients taking estrogen alone were lower (76.88 +/- 23.66 vs 95.91 +/-
      24.57 in group 1, 80 +/- 13.34 vs 96.91 +/- 18.97 in group 2) than pretreatment
      values. No significant difference in glucose levels was found after glucose load
      in the four groups. CONCLUSION. Women treated with estrogen alone have a tendency
      to a lower insulin response, which could indicate a greater insulin sensitivity.
      This effect seems to be more evident in transdermic administration than with oral
      administration. The addition of progestagen seems to wane the increase in insulin
      sensitivity induced by estrogens.

PMID- 9573749
TI  - Many factors can affect the prevalence of hypertension in obese patients: role of
      cuff size and type of obesity.
AB  - OBJECTIVE: To determine to what extent methodological errors, including
      measurements taken with inappropriate cuffs and/or inaccuracies in patient
      enrollment, can contribute to overestimating the prevalence of hypertension in
      overweight or obese women. EXPERIMENTAL DESIGN: Randomized and comparative
      investigation in overweight or obese outpatient women of the Obesity Clinic,
      Internal Medicine Institute, Chieti University. PATIENTS: In 1,791 overweight or
      obese women, randomly selected and stratified by age (41-60 years), blood
      pressure (BP) was taken with casual measurement in the morning. The entire study
      group was divided into two subgroups. In the first one, causal BP was measured
      with a standard-size cuff (RCS), while an appropriate large-size cuff was used
      for the second one (LCS). Patients of the latter subgroup were also divided by
      type of obesity (android and gynoid), based on their waist-to-hip ratio. RESULTS:
      In the LCS subgroup, the hypertension prevalence rate was strikingly lower among
      overweight and obese women, as well as in the younger and older age groups, when
      compared with the corresponding RCS subgroups (p < 0.001). The hypertension
      prevalence rate was higher for all android obese subjects (53%), including
      younger (34%) and older (64%) groups, when compared with gynoid obese patients
      (29%, 18% and 42%, respectively). CONCLUSIONS: A comparison of different reports
      on the prevalence of hypertension in obesity reveals considerable differences,
      due mainly to age, sex, race and income level. Nevertheless, our data seem to
      indicate that even after adjusting for the above-mentioned variables, two
      significant confounding factors, cuff hypertension and the prevalence of android
      obesity in the obese study population, could be responsible for over-estimating
      the prevalence of hypertension. It should be noted that for certain groups of
      overweight and obese women, the prevalence of hypertension becomes similar to the
      rate found among the general population, as reported in many large
      epidemiological surveys.

PMID- 9573750
TI  - Persistently low cardiac output predicts high mortality in newborns with
      cardiogenic shock.
AB  - BACKGROUND: Cardiogenic shock is an acute "unstable" state of circulatory
      dysfunction. OBJECTIVE: To evaluate the haemodynamic aspects of 45 newborn
      infants affected by cardiogenic shock, in relation to etiologies and the
      mortality rate. DESIGN: Retrospective, correlation study of etiologies, mortality
      rate and haemodynamic measurements by Doppler ultrasound parameters. PATIENTS: 45
      newborn infants with cardiogenic shock, Gestational Age (GA) 37 (34-41), Birth
      Weight (BW) 2750 (1600-3600) g and and a control group of 20 neonates [GA 38 (34
      40) wks, BW 2960 (1750-3800) g]. MEASUREMENTS: Left ventricular Cardiac Output
      (CO) was measured by a duplex scanner with pulsed Doppler and color flow mapping
      echocardiography in the first 48 hours of life. RESULTS: In healthy newborns CO
      was 240 mL/min/kg (210-280), in newborns with cardiogenic shock CO was 170
      mL/min/kg (f130-200), p < 0.01. The Stroke Volume was 1.80 mL/kg (1.70-1.90) in
      the control group and 1.20 (1.15-1.80) in the shocked group (p < 0.05); Heart
      Rate was 146 beats/min (130-160) and 160 beats/mm (140-194), (p < 0.01)
      respectively. Twenty-nine infants with cardiogenic shock had CO < or = 150
      mL/min/kg and 5 of them (17.2%) died; 16 neonates had CO > 150 mL/min/kg and only
      one (6.2%) died (p < .01). Twenty-six of 36 newborns with perinatal asphyxia had
      CO < or = mL/min/kg and 5 of them died, while only one of 10 infants with CO >
      150 mL/min/kg died. CONCLUSIONS: Our results show that persistently low CO (< or
      = mL/min/kg) during the first 48 hours life, in newborns with cardiogenic shock
      due to perinatal asphyxia is associated with a significantly higher mortality.

PMID- 9573751
TI  - Unilateral arterial reconstruction for aortoiliac occlusive disease.
AB  - METHODS: The outcomes of 234 arterial bypasses for aortoiliac occlusive disease
      were retrospectively analyzed. Surgical procedures included 60 bilateral aorto
      /iliofemoral bypasses, 140 unilateral aorto-/iliofemoral bypasses, and 34
      femorofemoral cross-over bypasses. Nineteen patients (13.6%) showed deterioration
      of the contralateral iliac artery after the initial unilateral operation. Of
      these patients, 11 patients underwent further surgical treatments; including 5
      unilateral aortofemoral operation bypasses, 2 iliac thromboendarterectomies, 2
      iliac PTA's, 1 femorofemoral bypass, and 1 bilateral aortofemoral bypass. The
      remaining 8 patients received conservative treatment because of their risk
      factors. The patency rate of the unilateral reconstruction has improved during
      the last 12 years according to our historical analysis. RESULTS: Our results
      demonstrate that unilateral vascular reconstruction is a valuable alternative to
      conventional bilateral reconstruction in unilateral symptomatic aortoiliac
      occlusive disease. CONCLUSIONS: Accurate preoperative diagnosis and early
      detection of the progression of sclerotic lesions on the contralateral side are
      the keys to successful results.

PMID- 9573752
TI  - Preoperative GnRH analogue in hysteroscopic metroplasty.
AB  - OBJECTIVE: To evaluate the effectiveness of Gonadotropin-Releasing Hormone
      analogue when administered preoperatively in hysteroscopic metroplasty. DESIGN:
      Prospective, comparative study. PATIENTS AND MAIN OUTCOME MEASURES: Sixty
      patients undergoing hysteroscopic metroplasty for septate uterus who were
      randomly allocated to pretreatment with two injections monthly of Gonadotropin
      Releasing Hormone analogue or to no pretreatment. To assess the outcome of
      surgery three parameters were used: operative time (minutes), fluid adsorption
      (ml) and intraoperative bleeding. RESULTS: No significant differences in the
      operating time (21.9 vs 22.9 min), fluid adsorption (395 ml, range 200-550 vs 515
      ml, range 250-650), intraoperative bleeding and failure rate were found between
      pretreated patients and controls. CONCLUSIONS: Preoperative treatment with
      Gonadotropin-Releasing Hormone analogue showed no advantage in hysteroscopic
      treatment of mullerian defects, but only an improvement, not statistically
      significant, in term of reduced operative time and fluid adsorption.

PMID- 9573753
TI  - Tubal patency after laparoscopic treatment of ectopic pregnancy.
AB  - OBJECTIVE: To evaluate operative course, tubal patency and reproductive
      performance after laparoscopic treatment of ectopic pregnancy in relation to
      initial human chorionic gonadotropin (hCG) values and to the kind of operation.
      DESIGN: Retrospective study. PATIENTS: Fourty-five patients affected by ectopic
      pregnancies: thirty-two treated with laparoscopic linear salpingotomy subvided
      into two groups depending on the hCG serum values < 10,000 mUl/ml (twenty
      patients: group 1) or > 10,000 mUl/ml (twelve patients Group 2), thirteen
      patients (Group 3) undergoing laparoscopic salpingectomy. Hysterosalpingographic
      examination was performed two or three months after surgery. MAIN OUTCOME
      MEASURES: Operative time, major surgical complications, tubal patency and
      pregnancy rate after surgery. RESULTS: Operative time was significantly (p <
      0.05) lower in both group 1 and 3 (22.5 +/- 3.2 and 19.1 +/- 6.3, respectively)
      than in group 2 (39.4 +/- 5.6). Bilateral patent tubes were observed in eighteen
      cases of group 1 (90%) and eight cases of group 2 (60%). No statistically
      significant differences were found between the pregnancy rate of both group 1
      (8/18) and 2 (3/8) and of group 3 (3/11). CONCLUSIONS: Reproductive outcome is
      similar in both conservative and destructive laparoscopic management of ectopic
      pregnancy: furthermore it shows a trend of improvement, not statistically
      significant, in conservative treatment.

PMID- 9573754
TI  - Manual lymphatic drainage for chronic post-mastectomy lymphoedema treatment.
AB  - BACKGROUND: The authors evaluated the chronic post-mastectomy lymphoedematous
      tissue and the effects of manual lymphatic drainage (Leduc method) with and
      without compressive bandage. METHODS: The arms were measured before and after
      physical therapy and the results were expressed as a percentage decrease.
      Physical therapy was performed first by manual lymphatic drainage only and after
      by manual lymphatic drainage plus compressive bandage. RESULTS: We observed that
      during manual lymphatic drainage plus compressive bandage the total percentage
      decrease of whole limb was the highest: 41.1 +/- 12.2% versus 30.4 +/- 15.8% (p <
      0.05). Clinical and physiopathological implication are discussed.

PMID- 9573755
TI  - Nitric oxide plasma levels in patients with chronic and acute cerebrovascular
      disorders.
AB  - BACKGROUND: The authors carried out a study on plasma level of nitrites, stable
      end-products of nitric oxide, aimed at investigating some features of the
      cerebral microvascular function in chronic and acute cerebrovascular disorders,
      METHODS: The series consists of 16 patients with chronic cerebral vascular
      disease, 11 patients with TIA, 28 patients with thrombotic stroke and 27 normal
      controls; the diagnosis was done on the basis of clinical, ultrasonographic and
      tomodensitometric findings. For each subject the determination of nitrate plasma
      levels by a method based on the colorimetric reaction (developed by nitrites
      dissolved in an acid solution containing sulfanilamide) was performed; this
      reaction yields quantitative results exactly corresponding to the amount of
      nitric oxide. RESULTS: In chronic cerebrovascular patients NO2-values
      tendentially higher (16.4 +/- 0.52 mumol/l) but not statistically different from
      those of controls (13.2 +/- 0.52) were obtained; also the values found in the
      group with TIA, even if slightly reduced (8.0 +/- 1.4 mumol/l), did not differ
      from controls; in the stroke group a significant (p < 0.05) reduction (6.4 +/-
      0.52 mumol/l), as compared to controls, was found. CONCLUSIONS: On the basis of
      these results and of the literature data on the physiopathological profile of NO,
      the authors suggest a compensatory increase of the basal tone of NO in chronic
      cerebrovascular diseases, while an impaired endothelial synthesis of the marker
      could play a critical role in TIA patients and more evidently in stroke patients,
      presenting a wide microvascular area completely and irreversibly excluded.

PMID- 9573756
TI  - The increased frequency of hypercholesterolemia in southern Italy is induced only
      by changing diet quality?
AB  - BACKGROUND: The purpose of this paper is to evaluate cholesterolemia and
      triglyceridemia in relation to BMI, alimentary habits and physical activity.
      DESIGN: We compare our epidemiological data with those obtained in other studies
      previously carried out in Campania: "CNR-ATS-RF2-OB43". SETTING: Campania
      (Italy). RESULTS: Data show an increase of these risk factors in Southern Italy
      from 1978 to 1989. In males, between 20 and 59 years the prevalence of
      hypercholesterolemia increases from 15.9% in 1978-1979 (CNR-RF2) to 17.8% in 1983
      1984 (ATS-OB43), and 20.6% in our own data (1988-1990). The pattern is similar
      for females: 14.4% (1978-79), 16.7% (1983-1984), and 18.6% (1988-1990). In males
      hypertriglyceridemia increases from 17% in 1978-1979, to 21.3% in 1983-1984 and
      36.2% in 1988-1990. In females from 9.8% to 12.4% and 18% respectively.
      CONCLUSIONS: This reality can be explained through the gradual changing of
      alimentary habits (high consumption of saturated fats and very little intake of
      vegetal fibres) and by reduced physical activity that contributes to the
      progressive BMI increase.

PMID- 9573757
TI  - Physiopathology of the renin-angiotensin system in the ovary.
AB  - The present review confirms the existence of the so-called "ovarian-derived
      prorenin-angiotensin cascade". It also describes the physiopathology of the
      system and, consequently, its role in the genesis of phenomena concerning
      reproductive function such as ovulation, steroid synthesis and folliculogenesis.
      Moreover, the "ovarian-derived prorenin-angiotensin cascade" appears to play an
      important role in the aetiopathogenesis of diseases such as ovarian tumours,
      ovarian hyperstimulation syndrome and ectopic pregnancy.

PMID- 9573758
TI  - Continuous hemodiafiltration during aortic arch aneurysm repair in chronic renal
      failure patient.
AB  - We report the successful repair of a distal aortic arch aneurysm in a patient
      with chronic renal failure following aneurysmectomy for a ruptured abdominal
      aorta. Perioperative use (during and up to 47 hrs after the operation) of
      continuous hemodiafiltration was useful for controlling fluid balance and uremia
      without any complicating hemodynamic instability. However, this should be
      restricted to the first two or three days after the operation, since it poses
      risk of significant thrombocytopenia.

PMID- 9573759
TI  - Acute myositis following autologus bone marrow transplantation (BMT).
AB  - A 4-year-old boy with acute myeloid leukemia developed acute myositis associated
      with refractory thrombocytopenia one month after autologous bone marrow
      transplantation (BMT). Clinical, electromyographic and biohumoral features were
      consistent with the diagnosis of myositis. The patient responded to
      corticosteroids, and 39 months after BMT he is in complete remission and has
      regained good muscle function. Although we could not determine with certainty the
      specific pathophysiologic mechanism of this complication, it should be pointed
      out that acute myositis can occur in the early post-BMT period.

PMID- 9573760
TI  - Undefined CD4 lymphocytopenia without clinical complications. A report of two
      cases.
AB  - A form of idiopathic CD4 lymphocytopenia (ICL) has been recently described. Its
      diagnostic criteria have been defined by the Centers for Disease Control (CDC),
      Atlanta. Associations of ICL with hepatitis C infection have been reported, while
      some ICL patients have presented abnormalities partly similar to those observed
      in common variable immunodeficiency (CVI). This paper illustrates the
      immunological pictures of two subjects with a CD4 deficiency confirmed in a
      series of peripheral blood lymphocyte subset determinations, but not associated
      with other cellular or humoral immunity abnormalities and accompanied by poorly
      significant clinical manifestations (no opportunistic infections). Patient one
      has been observed for a very long period. Her serological picture has been
      negative and she is free from hypergammaglobulinemia. HIV infection can thus be
      ruled out. Patient two has not required any specific treatment so far. The CDC's
      diagnostic criteria for ICL are not fully met in the two cases. Their pictures
      meet many, though not all of the CDC criteria for the diagnosis of ICL. It is to
      be hoped that a protracted follow-up will allow an assessment to be made of the
      natural history of the two cases.

PMID- 9573761
TI  - Imported tropical diseases in subjects with HIV infection.
AB  - The authors report a case of Plasmodium falciparum malaria and a case of
      lymphatic filariasis caused by Brugia malayi, imported by HIV-infected patients
      during trips in endemic countries. The clinical and laboratory picture, as well
      as treatment response of imported malaria and filariasis did not differ
      significantly in patients with HIV infection compared with immunocompetent
      subjects. The exposition to tropical diseases during exotic travels has to be
      taken into account, in the differential diagnosis of infectious disorders
      complicating the course of HIV disease.

PMID- 9573762
TI  - Treatment with colchicine and survival of patients with ascitic cirrhosis: a
      double-blind randomized trial.
AB  - BACKGROUND: In order to assess the role of colchicine in the survival of
      cirrhotic patients, 52 patients were studied. METHODS: The patients were divided
      into two groups, randomized according to age. There were no significant
      differences in age, sex, etiologic factors, or biological data. In addition to
      conventional therapy with diuretics, the first group was treated with colchicine
      of 1 milligram daily for 5 days a week, and the second group with a placebo.
      RESULTS: Under the action of colchicine, the diuretics were discontinued because
      the ascites disappeared in 37.93% of the colchicine group, vs 4.35% of the
      placebo group (p < 0.01). At time of discharge from the clinic, ascitic fluid
      disappeared respectively in 72.41% and 26.09% of cases (p < 0.001), whereas the
      recurrence in the follow-up period was 47.62% vs 83.33% (p < 0.1). CONCLUSIONS:
      Using Kaplan Meier survival curves, and comparing both groups with Logrank test
      during a period of 11 years it was found that survival of the colchicine group
      was 3 times greater than that of the placebo group (p < 0.001).

PMID- 9573764
TI  - Clinton proposes research increases.

PMID- 9573765
TI  - Research community mobilizes to defeat cloning legislation.

PMID- 9573763
TI  - Immunolocalization of fibronectin in recurrent minimal change glomerulonephritis
      kidney biopsy sections of two acute rejected renal transplant recipients.

PMID- 9573766
TI  - Congress to put intellectual property treaty into effect.

PMID- 9573767
TI  - [National Gastroenterology Week. Morelia, Mexico, 2-4 December 1997. Abstracts].

PMID- 9573768
TI  - The role Kentucky's dentists must play in preventing child abuse & neglect.
AB  - Dentistry must become more aware of its moral, legal, and ethical
      responsibilities in recognizing and reporting child abuse and neglect. All dental
      professionals must be aware of the seriousness of the problems of child
      maltreatment, and understand that children do not just get hurt in abuse and
      neglect, they often die as a direct result of their maltreatment. Unfortunately,
      victims of child abuse and neglect fall into only two categories--those who lived
      through it and those who did not.

PMID- 9573770
TI  - Efficacy of topical disinfectants.
AB  - A comparison of bactericidal activity of two surface disinfectants showed that
      both were highly effective. The glutaraldehyde-based disinfectant showed higher
      efficacy on roughed surfaces than the alcohol-based disinfectant. The study used
      a novel, and generally applicable, method to evaluate the surface killing
      potential of disinfectants.

PMID- 9573769
TI  - Ethical dilemma. What would you do?

PMID- 9573771
TI  - Oral health needs among children attending Louisiana public schools with health
      centers: phase I.

PMID- 9573772
TI  - Oral pathology biopsy service at the Louisiana State University School of
      Dentistry: status report 1995.

PMID- 9573773
TI  - Dentistry on the Internet: is there anything you can't find?

PMID- 9573774
TI  - Case presentation. Amyloidosis of the tongue.

PMID- 9573775
TI  - Implant update.

PMID- 9573776
TI  - Implant update.

PMID- 9573777
TI  - Case presentation. Lupus erythematosus with cutaneous and oral manifestations.

PMID- 9573778
TI  - Enameloplasty for esthetics.

PMID- 9573779
TI  - Converting a lower complete denture into an implant overdenture prosthesis.

PMID- 9573781
TI  - In vitro microleakage of CAD/CAM restorations cemented with a microfilled
      composite cement.

PMID- 9573780
TI  - Proliferative periostitis (Garre's osteomyelitis) arising as a result of a
      secondarily infected surgical defect.

PMID- 9573782
TI  - Allergic stomatitis.

PMID- 9573783
TI  - Effect of bleaching agents on chemical composition of enamel.

PMID- 9573784
TI  - Tobacco education for adolescents in Mississippi. A pilot project.

PMID- 9573785
TI  - Comparison of fit of CAD/CAM restorations using a direct and an indirect
      technique.

PMID- 9573786
TI  - Use of panoramic dental radiography as an aid in detection of patients at risk
      for stroke.

PMID- 9573787
TI  - Dental team's role in tobacco cessation.

PMID- 9573788
TI  - Evaluation of curing units used in private dental offices.
AB  - It is well known that numerous factors influence the light output of curing
      units, but many dentists are unaware that the output of their curing lights are
      inadequate. This study was conducted to evaluate the light intensity of visible
      light curing units in private dental offices and to assess their curing
      efficiency by measuring compressive strength of a light-cured resin. Also, in
      order to determine the maximum light intensity of the curing units, lamps,
      filters, and fiber optic bundles were replaced by new ones and curing efficiency
      remeasured. Light intensity was measured by employing a Quantum Radiometer LI-189
      at a wavelength of 470 +/- 40 nm using a bandpass filter. Compressive strength of
      a light-cured resin using the light units was measured employing an Instron
      Testing Machine at a crosshead speed of 1.0 mm/min. From the evaluation of 105
      light units, the light intensity ranged from 28 to 1368 W/m2 (0 approximately 500
      W/m2; 41.9%, 500 approximately 1000 W/ m2; 45.7%, 1000 approximately 1500 W/m2;
      12.4%). Light intensity of the light unit in private offices decreased 15.9
      approximately 82.1% compared to brand-new units. Reduction of light intensity
      impaired compressive strength of the light-cured resin to varying degrees (148.3
      approximately 279.9 MPa) compared with the highest value (317 MPa) obtained from
      brand-new light units. The replacement of the parts increased the light
      intensity, with maximum increases of 36.0% for lamps, 157.7% for filters, 46.2%
      for fiber optics, and 322.7% for all three parts. The results of this study
      indicated that the light intensities of the curing units used in private practice
      were lower than expected.

PMID- 9573789
TI  - Effect of eugenol-containing temporary cements on bond strength of composite to
      dentin.
AB  - The effect of temporary materials on shear bond strength of composite to dentin
      was investigated. Sixty previously impacted (caries-free) human third molars were
      embedded and sectioned horizontally at the pulp chamber and at the half of the
      crown. The samples were covered with ZOE, Temp Bond (eugenol-containing), Fermit,
      (temporary resin material, used without cementing) and Provicol, (eugenol-free,
      calcium hydroxide-containing). All specimens were stored in saline for 10 days.
      After mechanical cleaning the dentin was pretreated with a dentin bonding agent
      (Syntac), and the composite columns were applied. Debonding was performed using a
      Zwick Universal Testing Machine (cross-head speed 1.5 mm/min). The mode of
      failure was noted using a light microscope, and the thickness of the dentin at
      the composite/dentin interface was measured. The median shear bond strength
      values for the treated and control samples were: ZOE 7.46 MPa, Temp Bond 10.22
      MPa, Fermit 6.49 MPa, Provicol 8.43 MPa, and control 10.06 MPa. No two groups
      were significantly different at the 0.05 level (one-way ANOVA and Scheffe test).
      In all groups the predominant mode of failure was adhesive and there was a slight
      tendency towards lower shear bond strength values at lower values for the
      thickness of the dentin. Under the conditions described the use of eugenol
      containing temporary cements had no adverse effect on shear bond strength of a
      dual-curing composite luting cement to dentin.

PMID- 9573790
TI  - Effect of eugenol-containing temporary cements on bond strength of composite to
      enamel.
AB  - The purpose of this study was to find out the degree to which eugenol-containing
      temporary cements or temporary filling materials affected shear bond strength of
      a dual-cure resin luting cement to acid-etched enamel. For this purpose 56 human
      caries-free third molars were embedded in acrylic resin and cross sectioned
      mesiodistally. One of the corresponding halves was covered with Temp-Bond
      (eugenol-containing, Group 1), Provicol (eugenol-free, Group 2), ZOE (Group 3),
      and eugenol (Group 4). The other half of each sectioned tooth was kept clean and
      served as a control. After 1 week the cements were removed; the pure eugenol
      group (Group 4) was terminated after 24 hours. Plastic cylinders were filled with
      Dual Cement and placed on the etched enamel and light cured. Shear bond strength
      data were recorded using a Zwick Universal Testing Machine, and the mode of
      failure was diagnosed using a light microscope. Significant differences in shear
      bond strength could neither be found between the treated halves and the controls
      nor among the four groups pretreated with eugenol-containing or eugenol-free
      temporary cements. Based on the results of this study, no adverse effects of
      eugenol on shear bond strength of a resin luting cement to enamel could be found.

PMID- 9573791
TI  - Shear bond strengths of six bonding systems using the pushout method of in vitro
      testing.
AB  - The newest generation of bonding systems consolidates multiple components into
      fewer containers in order to simplify clinical procedures and save clinicians
      time. Six newer adhesive systems (Scotchbond Multi-Purpose Plus, PROBOND,
      OptiBond FL, Prime & Bond, One Step, and Tenure Quik) were tested for in vitro
      shear bond strength (SBS) of a hybrid composite to both superficial and deep
      dentin at 24 hours and 6 months employing a pushout test method. Results showed
      significant differences in SBS between superficial and deep dentin for both 1-day
      and 6-month values for all adhesive systems except Tenure Quik. The SBS of
      OptiBond FL increased significantly for both superficial and deep dentin after 6
      months' storage in 37 degrees C water. None of the other adhesive systems showed
      a significant change in SBS at 6 months. There appear to be several advantages to
      the testing method.

PMID- 9573792
TI  - Clinical evaluation of a polyacid-modified resin composite (compomer).
AB  - The purpose of this study was to evaluate the clinical performance over 1 year of
      the proprietary polyacid-modified composite resin Dyract (DeTrey Dentsply). Forty
      one restorations (five in interproximal anterior cavities, 36 in noncarious
      cervical cavities) were placed following the manufacturer's instructions. After 1
      year, one of the cervical restorations had been lost, and eight restorations
      showed some degree of marginal discoloration. Overall, Dyract showed mixed
      results as a tooth-colored restorative material in nonstress-bearing areas. The
      long-term clinical performance and reasons for incipient marginal discoloration
      need further investigation.

PMID- 9573793
TI  - Artificial secondary caries around two new F-containing restoratives.
AB  - Replacement of restorations due to secondary caries is a continuing problem in
      restorative dentistry. This investigation evaluated the ability of two new light
      cured fluoride-containing restorative materials to inhibit caries in vitro. Class
      5 cavities were prepared in buccal and lingual surfaces of 20 extracted
      premolars. The occlusal cavosurface margin of each preparation was on enamel and
      the gingival cavosurface margin was on root surface. The four materials used
      were: glass-ionomer cement (Fuji II), composite resin (Silux Plus), light-cured
      glass ionomer (Vitremer), and compomer (Dyract). After 5 weeks in an acid gel for
      caries-like lesion formation, the teeth were sectioned longitudinally and
      examined with polarized light. The results showed that use of a light-cured glass
      ionomer and/or compomer may prevent both secondary caries around restorations and
      primary caries in surface enamel adjacent to the restorations.

PMID- 9573794
TI  - Polymerization of composite resins: argon laser vs conventional light.
AB  - The purpose of this in vitro study was to compare polymerization of composite
      resins, as indicated by microhardness, at increasing depths using an argon laser
      versus a conventional light. For this, a microfill (Silux Plus) and a hybrid
      (TPH) composite resin were used. Five specimens per group were prepared by
      injecting composite into a rectangular split Teflon mold 3 x 3 x 8 mm. Specimens
      were then polymerized by either a 40-second exposure to the conventional visible
      light (VL) or a 30-, 20-, or 10-second exposure to the argon laser (AL).
      Specimens were stored in a light-proof container for 24 hours at 37 degrees C,
      then Knoop hardness was determined. Four measurements were taken for each
      specimen at depths of 0, 1, 2, 3, and 4 mm from the exposed surface. No
      significant differences were found in surface hardness for either the microfill
      or hybrid composite regardless of light source or exposure time. For the
      microfill composite, at 1, 2, 3, and 4 mm depths, VL40 and AL30 exposures
      produced comparable hardness, which was significantly greater than that found for
      AL20 and AL10. At a depth of 4 mm, exposure to VL40 resulted in significantly
      greater hardness compared to AL20. With AL10 exposure, the composite was too soft
      to determine hardness. The hybrid composite had comparable hardness to a depth of
      3 mm for VL40, AL30 and AL20.

PMID- 9573795
TI  - The effect of amalgam overhangs on alveolar bone height as a function of patient
      age and overhang width.
AB  - The purpose of this study was to compare the effects of amalgam restorations with
      and without overhangs on alveolar bone loss via digitized radiographs for
      subjects of varying ages and overhang widths. The first phase of this study
      compared the alveolar bone loss among teeth with clinically acceptable two
      surface amalgam restorations with a control surface on the same tooth. The second
      phase was similar to the first phase with the exception that it compared
      defective amalgam restorations (those containing amalgam overhanging approximal
      margins) with the control surface on the same tooth. The collected data showed a
      significant loss of alveolar bone as a result of amalgam overhang presence (P <
      0.02). However, overhang width and patient age did not affect the significance of
      the detrimental effects of the amalgam overhangs. Overall alveolar bone height
      was seen to decrease with patient age, independent of amalgam restorations.
      Digital radiography was seen to be an accurate method for evaluating alveolar
      bone height changes due to the local environment created by overhanging amalgam
      margins.

PMID- 9573796
TI  - Characterization of serum antibodies to Porphyromonas gingivalis in individuals
      with and without periodontitis.
AB  - Although Porphyromonas gingivalis is a defined pathogen in periodontal disease,
      many subjects control the infection without experiencing loss of attachment.
      Differences in host susceptibility to the disease may be reflected in the pattern
      of humoral antibodies against specific P. gingivalis antigens. The aim of this
      study was to determine the presence of antibodies against immunodominant P.
      gingivalis antigens as well as the isotype and subclass of anti-P. gingivalis
      antibodies against outer membrane antigens in four groups of patients: P.
      gingivalis-positive, 1) with and 2) without periodontitis, and P. gingivalis
      negative, 3) with and 4) without periodontitis. Antigens of molecular weight 92,
      63, and 32 kDa and lipopolysaccharide were found to be immunodominant. Group 1
      subjects showed a significantly higher response to the 92 and 63 kDa antigens
      compared with other groups. The response to lipopolysaccharide was significantly
      higher in group 1, and lower in group 4 than in groups 2, 3. Immunoglobulin G1
      (IgG1), IgG2 and IgM antibodies against P. gingivalis outer membrane were present
      in all subjects, while only some subjects were seropositive for IgG3, IgG4 and
      IgA. There were no differences in concentrations for IgG1, IgG3 and IgM. The IgG2
      concentration in group 4 was significantly higher than in groups 1 and 2, while
      the IgG4 concentration in group 4 was significantly lower than in other groups.
      The frequency of seropositivity for IgG4 and IgA was lowest in group 4, while
      IgG3 seropositivity was almost exclusively seen in healthy patients in groups 2,
      4. These findings suggest that the presence of IgG3 may reflect non
      susceptibility to the disease, while lack of IgG4 may be indicative of
      periodontal health and lack of infection.

PMID- 9573797
TI  - Effect of immune T cells derived from mucosal or systemic tissue on host
      responses to Porphyromonas gingivalis.
AB  - The purpose of this study was to compare the effects of immune T cells derived
      from mucosal and systemic tissues on specific humoral responses to the
      periodontal pathogen Porphyromonas gingivalis and to determine the effect these
      responses have on periodontal bone loss in an experimental rat model. T cells
      were derived from either the spleen or Peyer's patches of conventional Fischer
      rats given live P. gingivalis by the oral route and were adoptively transferred
      into groups of nude Fischer rats. A group of nude rats to which no T cells were
      transferred served as control. Within 24 h of the adoptive cell transfer, animals
      from all groups were orally challenged with live P. gingivalis. Serum and
      salivary responses were seen in rats given immune T cells, whereas a low,
      variable serum IgM and no serum IgG or salivary IgA response was detected in the
      control nude rats, indicating that the major host responses to P. gingivalis
      whole-cell antigens were T-cell dependent. Rats given immune Peyer's patch
      derived T cells exhibited a different serum IgG and salivary IgA immune response
      pattern than animals given immune splenic T cells. A higher serum IgG, especially
      IgG2b, antibody response and less horizontal bone loss was seen in rats given
      splenic than Peyer's patch-derived T cells. Although some differences were seen
      in the levels of salivary IgA early in the study in the two experimental groups,
      the levels of IgA were comparable by the termination of the experimental period.
      Furthermore, no difference was seen in the amount of vertical bone support in
      these two groups, which was greater than in the controls. These results suggest a
      role for serum IgG and salivary IgA in periodontal disease protection. The
      presence of high serum IgG2b antibody activity suggest the involvement of Th1
      like cells in the response, whereas salivary IgA antibodies indicates the
      participation of Th2-like cells. These results suggest that the balance between
      Th1 and Th2-like cells within the systemic and mucosal compartments and the
      humoral immune responses to P. gingivalis they mediate are important in
      determining whether the responses induced are protective against experimental
      bone loss after oral challenge with the periodontal pathogen P. gingivalis.

PMID- 9573798
TI  - Oral immunization with recombinant Salmonella typhimurium expressing a cloned
      Porphyromonas gingivalis hemagglutinin: effect of boosting on mucosal, systemic
      and immunoglobulin G subclass response.
AB  - Live avirulent Salmonella typhimurium are convenient vaccine vectors for the
      delivery of recombinant antigens for the induction of mucosal and systemic
      immunity. The hagB gene encodes a hemagglutinin of Porphyromonas gingivalis, a
      suspected causal agent in human adult periodontal disease. In previous studies,
      we have shown that hagB can be expressed in avirulent S. typhimurium and is
      immunogenic when given orally to mice. In this study, we evaluated recall
      responses in both serum and mucosal secretions after boosting. In addition, we
      have examined the immunoglobulin G (IgG) subclass response in serum to both HagB
      and the Salmonella carrier. Mice were orally immunized with S. typhimurium
      expressing the hagB gene and then boosted 14 weeks later. Responses were measured
      through 27 weeks. Both primary and recall IgG and IgA responses were seen in
      serum to the purified HagB as well as to the Salmonella carrier. Likewise,
      mucosal primary and recall responses were seen in saliva, fecal extracts and
      vaginal washes although the kinetics of the responses differed. The anti-HagB
      response in serum was dominated by IgG2a during the peak of primary response,
      prior to boosting and during the peak of the recall response. The anti-S.
      typhimurium response shifted from predominantly IgG3 following primary
      immunization to IgG2a after boosting. The IgG1 response was minimal against each
      antigen. This pattern of IgG subclass distribution is consistent with a Th1-type
      response. These data indicate that avirulent S. typhimurium is capable of
      delivering a putative virulence factor from P. gingivalis and inducing a primary
      and recall response in both serum and secretions and provides a means of studying
      P. gingivalis virulence factors and for the development of a potential vaccine.

PMID- 9573799
TI  - Structural integrity of infant salivary immunoglobulin A (IgA) in IgA1 protease
      rich environments.
AB  - IgA1 protease-secreting Streptococcus mitis often dominate the oral flora of the
      neonate and young infant at a time when salivary IgA concentrations are low and
      usually enriched in the secretory IgA1 subclass. To study the possible influence
      of these degradative enzymes on emerging host immunity, the presence of IgA1
      protease-secreting streptococci was related to the structural integrity of
      salivary IgA in 24 infants who were between 3 and 18 weeks of age. At least one
      IgA1 protease-secreting strain could be isolated from the oral mucosa of 79% of
      the infants and comprised a mean of 38% of the total streptococcal flora of these
      infants. Chromatographic analyses of resting whole saliva from 16 infants
      revealed, however, that 95% of the secretory IgA (range 88-100%) remained intact,
      indicating that minimal immediate IgA proteolysis occurred in the bulk salivary
      phase. Proteolysis of infant salivary IgA, presumably by indigenous IgA1
      protease, could be observed after extended (more than 7 h) in situ incubation of
      whole saliva at 37 degrees C. Salivary IgA antibody activities to S. mitis
      components were demonstrated by Western blot in infants colonized with an IgA1
      protease-secreting flora. Preliminary evidence suggested that salivary antibody
      activity in some infants may be directed to IgA1 protease. Thus, the infant's
      antibody defenses not only appear very early in life but are substantively intact
      in the bulk salivary phase, even when the oral cavity is colonized with IgA1
      protease-secreting streptococcal flora.

PMID- 9573800
TI  - Identification of hemolytic activity in Prevotella intermedia.
AB  - Hemolysin production was measured in strains of Prevotella intermedia. Zones of
      beta-hemolysis were detected on agar plates supplemented with either sheep,
      rabbit or human erythrocytes. A standard tube assay was performed on cell
      suspensions of the organism to measure hemolytic activity, which was found to be
      dose dependent, eliminated by heat treatment, and saturable with increasing
      concentrations of blood. Growth-phase experiments suggested that hemolysin
      production was increased during logarithmic growth and was reduced during
      stationary phase. Cell fractionation, performed on several strains of P.
      intermedia, localized the activity in the outer membrane and in cell vesicles.
      The biological implication of this study is that P. intermedia, by virtue of its
      hemolytic activity, is capable of liberating the hemoglobin from erythrocytes,
      thereby acquiring an essential nutrient, iron, for its metabolism.

PMID- 9573801
TI  - Effect of red blood cells on the growth of Porphyromonas endodontalis and
      microbial community development.
AB  - Establishment of a microbial community in the root canal system depends on
      numerous factors, of which nutrient availability may be one of the most
      important. We hypothesized that the presence of red blood cells or hemoglobin in
      this environment could cause shifts in microbial composition of communities,
      resulting in organisms such as Porphyromonas endodontalis becoming more dominant.
      An in vitro model system using mixed, batch cultures was performed with the
      bacteria P. endodontalis, Fusobacterium nucleatum, Peptostreptococcus micros and
      Campylobacter rectus. Bacteria were cultured in media with or without the
      addition of washed red blood cells, hemoglobin, or serum. Cyclic growth studies
      revealed that P. endodontalis was lost from the community of organisms after
      three cycles. However, inclusion of red blood cells resulted in establishment of
      this organism. Moreover, red blood cells added to pure cultures of P.
      endodontalis substantially enhanced growth and protected the organisms from
      oxygen. We conclude that the presence of red blood cells could result in shifts
      of microbial communities of organisms within the root canal system.

PMID- 9573802
TI  - Putative heat shock protein 70 gene from Actinobacillus actinomycetemcomitans:
      molecular cloning and sequence analysis of its gene.
AB  - We have cloned and sequenced two overlapping fragments of chromosomal DNA from
      Actinobacillus actinomycetemcomitans. The nucleotide sequence contained two open
      reading frames. The deduced amino acid sequences of the two open reading frames
      showed significant homology with the heat shock proteins hsp70 and hsp40 of other
      organisms respectively. The upstream open reading frame consisted of 1902 bp,
      corresponding to 634-amino-acid residues. The CAA codon for glutamines was
      frequently seen in hsp70, i.e., in 30 of 32 glutamines (93.8%). The spacing
      region between the two open reading frames was unusually long compared with other
      prokaryotic organisms. A number of unique and distinguishing features of the
      sequences in the hsp70 family were verified, and it was found that a particular
      spacing sequence between the hsp70 and hsp40 gene loci can be used to identify A.
      actinomycetemcomitans from the periodontal pocket.

PMID- 9573803
TI  - Differentiation of clinical isolates of Actinobacillus actinomycetemcomitans
      using an insertion sequence, ISAa1.
AB  - We previously identified an IS200-like sequence (ISAa1) in the genome of
      Actinobacillus actinomycetemcomitans FDC Y4. One or more hybridizing bands to the
      ISAa1 probe were detected in each of several reference strains, representing
      three of the serotypes (a through c) of A. actinomycetemcomitans. In this study,
      we examined whether a restriction fragment-length polymorphism (RFLP) with ISAa1
      as a probe could differentiate clinical isolates. One or more hybridizing bands
      were detected in each of the 27 strains examined, which could be divided into
      seven groups according to restriction fragment-length polymorphism pattern.
      Several strains were observed with identical restriction fragment-length
      polymorphism types but with different serotypes. Conversely, strains were also
      observed with differing restriction fragment-length polymorphism types and
      identical serotypes.

PMID- 9573804
TI  - Functional analysis of pVT745, a plasmid from Actinobacillus
      actinomycetemcomitans.
AB  - Plasmid pVT745 is a 25.1-kb replicon isolated from Actinobacillus
      actinomycetemcomitans strain VT745. A previous report described the hybridization
      of pVT745 in 5 strain-specific patterns to chromosomal DNA from 15 other A.
      actinomycetemcomitans strains. However, pVT745 does not share homology with the
      chromosome of the strain from which it was isolated, VT745. It was hypothesized
      that the shared areas of homology might represent insertion sequence elements
      and/or transposons possibly encoding resistance to one or more antibiotics. An
      antibiogram of strain VT745 demonstrated that this strain was uniformly
      susceptible to all antibiotics examined. Because insertion sequence elements and
      transposons are mobile genetic elements, a series of cell passaging experiments,
      followed by Southern hybridization was conducted in a attempt to detect
      transposition of pVT745 homologous DNA within the chromosomes of several A.
      actinomycetemcomitans strains. The results of these experiments suggested
      stability of the homologous DNA both within the chromosome and on the plasmid. It
      was also possible that pVT745 represented a lysogenic bacteriophage. Phage
      induction experiments were conducted under conditions that induced a previously
      described A. actinomycetemcomitans lysogenic phage, but no phage could be induced
      from strain VT745. Attempts to obtain isolates of VT745 cured of pVT745 were also
      unsuccessful.

PMID- 9573805
TI  - Acid tolerance and acid-neutralizing activity of Porphyromonas gingivalis,
      Prevotella intermedia and Fusobacterium nucleatum.
AB  - The tolerance to acid and the acid-neutralizing activity of three important
      periodontopathic bacteria, Porphyromonas gingivalis, Prevotella intermedia and
      Fusobacterium nucleatum were studied. P. gingivalis strains grew only at neutral
      pH and did not utilize glucose, whereas strains of P. intermedia and F. nucleatum
      could grow under acidic conditions and increased their growth by utilizing
      glucose. P. gingivalis tended to raise the culture pH during growth. P.
      intermedia and F. nucleatum raised the culture pH during growth in the absence of
      glucose, while in the presence of glucose they decreased the pH. Resting cell
      suspensions of all the bacteria raised the pH in the presence of tryptone and
      casamino acids. Acid-neutralizing activity was confirmed by measuring base
      production at a fixed pH with a pH-stat. During neutralization, the cells
      produced cytotoxic substrates, ammonia and organic acids (butyric, isobutyric and
      isovaleric acids by P. gingivalis; isovaleric and succinic acids by P.
      intermedia; propionic and butyric acids by F. nucleatum). These findings suggest
      that deamination of amino acids into ammonia and organic acids occurs
      simultaneously with base production, resulting in acid neutralization. These
      results could partially explain the survival of P. intermedia and F. nucleatum in
      both supragingival and subgingival plaque and the apparent restriction of P.
      gingivalis to subgingival plaque. The former bacteria may aid in creation of an
      environment fostering colonization of subgingival plaque by P. gingivalis.

PMID- 9573806
TI  - Nasal immunization of humans with dehydrated liposomes containing Streptococcus
      mutans antigen.
AB  - Five healthy female adult volunteers were intranasally immunized twice (7-day
      interval) with 250 micrograms of a crude glucosyltransferase (GTF) preparation
      from Streptococcus mutans in liposomes. Parotid saliva, nasal wash, and serum
      were collected prior to and at weekly intervals for 6 weeks following the first
      immunization for analysis of anti-GTF activity by enzyme-linked immunosorbent
      assay. The levels of IgA1 anti-GTF activity increased in the nasal wash from all
      five individuals after immunization. Increases in salivary IgA1 and IgA2 anti-GTF
      activities were observed to a lesser extent. Increased serum IgM and IgA (but not
      IgG) anti-GTF activities were seen in immunized subjects. Nasal immunization with
      a dehydrated liposome-protein vaccine was effective in inducing an apparent
      secretory IgA antibody response, which was primarily of the IgA1 subclass. These
      results provide the first evidence of the effective use of a nasal liposome
      protein vaccine in humans.

PMID- 9573807
TI  - Quantitative assessment of inflammatory cytokine gene expression in chronic adult
      periodontitis.
AB  - Adult periodontitis is a chronic destructive disease characterized by an
      interaction between gram-negative bacteria and the host inflammatory response.
      Microbial substances such as lipopolysaccharide can activate host cells, e.g.,
      macrophages, fibroblasts and keratinocytes, to secrete proinflammatory cytokines
      including tumor necrosis factor alpha and interleukin 1 beta (IL-1 beta). This
      study examined the hypothesis that periodontitis tissue contains increased levels
      of cytokines that promote osseous and connective tissue destruction. To test this
      hypothesis, diseased and healthy gingival biopsies were examined for differences
      in the expression of cytokine mRNA for the pro-inflammatory cytokines tumor
      necrosis factor alpha and IL-1 beta and the anti-inflammatory cytokine IL-1ra
      using quantitative reverse transcriptase polymerase chain reaction and in situ
      hybridization methods. The levels of tumor necrosis factor alpha and IL-1ra mRNA
      were shown to be significantly higher in diseased than healthy tissues.
      Additionally, a significantly correlated expression of IL-1 beta and IL-1ra mRNA
      was seen in all tissue examined. Analysis of tissue sections by
      immunohistochemical and in situ hybridization techniques revealed a mononuclear
      cell infiltrate that consisted of a higher average number of cells staining
      positive for tumor necrosis factor alpha mRNA, CD14, and CD3 in the diseased than
      healthy tissues. Although both diseased and healthy tissues expressed IL-1 beta
      and IL-1ra mRNA in the epithelium, the diseased tissue biopsies expressed more IL
      1 beta and IL-1ra mRNA in the connective tissue. These results implicate the
      potential involvement of both the pro- and anti-inflammatory cytokines in the
      regulation of the chronic inflammatory disease adult periodontitis.

PMID- 9573808
TI  - Cytotoxic effects of short-chain carboxylic acids on human gingival epithelial
      cells.
AB  - Previous studies showed that foods that are retained on the dentition can
      accumulate high levels of short-chain carboxylic acids (acetic, formic, lactic
      and propionic). Since gingival epithelium is the first periodontal tissue to be
      challenged by oral factors, a study was undertaken to determine whether short
      chain carboxylic acids can affect epithelial cells in vitro. Immortalized human
      oral epithelial cells were grown in supplemented keratinocyte growth medium at 37
      degrees C, and the effects of short-chain carboxylic acids were determined with
      tetrazolium-based and trypan blue exclusion assays. Low concentrations of short
      chain carboxylic acids inhibited the growth of human oral epithelial cells, while
      higher concentrations led to cell death. The effects of short-chain carboxylic
      acids on the cells were dose-dependent and varied among the individual acids
      (propionate > formate > lactate > acetate). Growth inhibition was partly
      reversible and growth resumed after removal of the acids. However, the time
      needed for recovery of the cells increased with short-chain carboxylic acids
      concentration, consistent with progressively greater damage to the cells at
      higher short-chain carboxylic acids concentrations. The observed effects of short
      chain carboxylic acids on gingival cells in vitro supported our hypothesis that
      short-chain carboxylic acids can damage the integrity of gingival epithelium in
      situ.

PMID- 9573809
TI  - Differentiation of Veillonella atypica, Veillonella dispar and Veillonella
      parvula using restricted fragment-length polymorphism analysis of 16S rDNA
      amplified by polymerase chain reaction.
AB  - Veillonella atypica, Veillonella dispar and Veillonella parvula cannot be
      reliably distinguished by conventional phenotypic tests, including the API ZYM
      test. In this study, restricted fragment-length polymorphism (RFLP) analysis of
      16S rDNA amplified by polymerase chain reaction (PCR) was used to generate
      restriction profiles of the type strains of V. atypica, V. dispar and V. parvula
      and 20 Veillonella strains isolated from oral sites. 16S rRNA gene sequences from
      isolated genomic DNA samples were amplified by PCR. PCR products were purified
      and characterized by single digestion with 13 restriction endonucleases. Among
      them, Mn/I was found to discriminate the respective reference strains, and the
      clinical isolates were assigned to one of the three species on the basis of their
      restriction profiles by digestion with Mn/I. Thus, RFLP analysis of PCR-amplified
      16S rDNA, using Mn/I, is a rapid and reliable method for the differentiation of
      V. atypica, V. dispar and V. parvula.

PMID- 9573810
TI  - High incidence of Staphylococcus aureus from dentures and tongues of maxillary
      resection patients.
AB  - The incidence and virulence of Staphylococcus aureus from upper dentures and
      tongues of maxillary resection and edentulous patients were examined. The
      incidence rates of S. aureus on dentures and tongues from the 8 maxillary
      resection patients were significantly higher than those from the 20 maxillary
      edentulous patients. Some S. aureus strains in both patient groups were resistant
      to antibiotics, and 1 methicillin-resistant S. aureus strain was isolated in each
      group. Exfoliative toxin was not produced, whereas diverse types of enterotoxin
      were detected in 4 of the 8 maxillary resection patients and in 3 of 13 maxillary
      edentulous patients. These findings show that S. aureus inhabits dentures and
      tongues of maxillary resection patients more often than those of maxillary
      edentulous patients and that some strains have potential virulence, suggesting
      that maxillary resection patients are potentially more exposed to a threat from
      S. aureus and would be the carriers.

PMID- 9573811
TI  - Phenotypic and genotypic characterization of oral yeasts from Finland and the
      United States.
AB  - A total of 4-22 isolates of oral yeasts per subjects from 48 yeast-positive
      Finnish and American subjects (25 females and 23 males) were phenotyped and
      genotyped to determine the frequency of simultaneous oral carriage of multiple
      yeast taxa. An oral sample from either periodontal pockets, oral mucosa or saliva
      was obtained. All subjects yielded Candida albicans and 3 subjects an additional
      yeast species (Candida krusei, Candida glabrata or Saccharomyces cerevisiae). The
      API 20C Aux kit distinguished 9 different carbohydrate assimilation profiles
      among the C. albicans isolates. Thirty-eight of 46 C. albicans biotype I isolates
      were categorized in a single numerical profile. PCR analysis, using a random
      primer OPA-03 and a repetitive primer (GACA)4, detected 2 major genotypic groups
      among the C. albicans isolates; 44 subjects showing isolates with a "typical" PCR
      profile and 4 subjects isolates with an "atypical" PCR-profile. The "atypical"
      PCR-profile was similar to that of Candida dubliniensis. All C. albicans isolates
      assimilated xylose, except 5, including the 4 with an "atypical" PCR-profile. No
      difference was found in distribution of oral yeast species, and of C. albicans
      phenotypes and genotypes between Finnish and American subjects. The present PCR
      method may offer a rapid and easy means of distinguishing oral Candida species.

PMID- 9573812
TI  - In vitro antimicrobial susceptibility of periodontopathic Actinobacillus
      actinomycetemcomitans to roxithromycin and erythromycin.
AB  - The in vitro minimal inhibitory concentrations (MIC) and minimal bactericidal
      concentration (MBC) of roxithromycin and erythromycin against Actinobacillus
      actinomycetemcomitans were evaluated. Sixty-seven different A.
      actinomycetemcomitans isolated from periodontal pockets of 101 subjects with
      different forms of early-onset and adult periodontitis and three reference
      strains of A. actinomycetemcomitans (ATCC 29522, ATCC 29523, and NCTC 9710) were
      included in this study. Erythromycin showed poor in vitro activity against A.
      actinomycetemcomitans; roxithromycin, on the contrary, exhibited good in vitro
      activity. Moreover, roxithromycin showed the best in vitro antimicrobial activity
      against 17 serotype a and 12 serotype c subpopulations of A.
      actinomycetemcomitans; against 38 serotype b subpopulation of A.
      actinomycetemcomitans, roxithromycin was consistently active. Roxithromycin
      exhibited MBC values usually equal to, or one-fold higher than MIC values. All
      the MBC values of erythromycin were three- to four-fold higher than the
      respective MIC result. Since roxithromycin is characterized by high
      concentrations in serum and good penetration and diffusion into gingival tissue,
      it could be expected to pass into the gingival crevicular fluid at levels
      sufficiently high to inhibit A. actinomycetemcomitans in vivo. These data
      indicate that roxithromycin might be a potential candidate for therapeutic trials
      in patients with A. actinomycetemcomitans-associated periodontitis.

PMID- 9573813
TI  - An inexpensive solid medium for obtaining colony-forming units of oral
      spirochetes.
AB  - A method for the enumeration of colony-forming units of oral anaerobic
      spirochetes in new oral spirochete agarose (NOS-A) medium was described recently.
      However, the high cost of agarose limits the extent to which large assays can be
      carried out. Accordingly, a search for an inexpensive gelling agent that remains
      molten at 37 degrees C and gels at 25 degrees C was undertaken. Varying amounts
      of Noble agar or Bacto agar (0.5 to 1.5%, w/v) were mixed with varying amounts of
      gelatin (0.5 to 1.0%, w/v) in NOS medium. NOS medium containing 0.5% gelatin-0.5%
      Noble agar (NOS-GN) or 0.5% gelatin-0.5% Bacto agar (NOS-GB) met the above
      criteria. NOS-GN and NOS-GB media yielded higher colony-forming units with
      Treponema denticola than NOS-A medium in that order. However, all three media,
      NOS-GN, NOS-GB and NOS-A, performed equally well in the recovery of viable counts
      of T. vincentii. The NOS-GN medium was not liquefied by subgingival bacteria or
      two gelatinase-producing species of bacteria, Bacillus subtilis and
      Staphylococcus aureus. Thus NOS-GN medium is the recommended medium both in cost
      and performance for obtaining colony counts of spirochetes.

PMID- 9573814
TI  - Absence of Porphyromonas asaccharolytica, Bacteroides fragilis and Chlamydia
      pneumoniae in human subgingival plaque.
AB  - Little is known about the presence of common medical pathogens in the human oral
      cavity. Using a 16S rRNA-based PCR identification method, this study determined
      the occurrence of Porphyromonas asaccharolytica, Bacteroides fragilis and
      Chlamydia pneumoniae in subgingival plaque from 50 adults with advanced
      periodontitis. Each patient contributed samples from 3 deep periodontal pockets
      collected by paper points. The PCR primers were for P. asaccharolytica 5'-CTC TAG
      CTA GAG TGT ACT GG-3' and 5'-ATA GGG TTT ATA GAT TAG CTC TCT-3', for B. fragilis
      5'-AAT GAT TCC GCA TGG TTT CAT TA-3' and 5'-GCG GTG ATT GCT CAC TGA CA-3', and
      for C. pneumoniae 5'- TGA CAA CTG TAG AAA TAC AGC-3' and 5'-CGC CTC TCT CCT ATA
      AAT-3'. The primers yielded a single amplicon with the respective reference
      strains and produced no amplicon with colonies of 25 groups of oral organisms.
      None of the three test species were detected in any of the 50 pooled subgingival
      samples tested. P. asaccharyolytica, B. fragilis and C. pneumoniae do not seem to
      be part of the periodontopathic microbiota in humans.

PMID- 9573815
TI  - Subgingival microbiota of shallow periodontal pockets in individuals after head
      and neck irradiation.
AB  - This study aimed at investigating the subgingival plaque microorganisms of
      shallow pockets (< or = 5 mm) in subjects who previously received irradiation in
      the head and neck region for treatment of nasopharyngeal carcinoma. Direct
      microscopy and anaerobic culture were used. Subgingival paper point samples were
      taken from 6 tooth-sites (one/sextant) per subject for direct microscopy (n =
      108). Another set of paper points was taken from the deepest of the previously
      selected sites (one per subject) with: group A) no bleeding on probing to the
      sulcus depth (n = 9) and group B) bleeding on probing to the sulcus depth (n = 6)
      for microscopic and anaerobic culture study. Under the microscope, the microflora
      was found to be a complex mixture comprising gram-positive and gram-negative
      cocci, rods and filaments, fusiforms, curved rods and spirochetes. Low level of
      fungi were observed and mycelia were occasionally detected. There was no
      significant variation in the plaque bacterial morphotypes observable according to
      sites of isolation and no significant difference between group A and group B in
      morphotypes of the different microflora. The predominant cultivable microflora
      comprised several species of facultative and obligate anaerobic bacteria:
      Gemella, Peptostreptococcus, Staphylococcus, Stomatococcus, Streptococcus,
      Actinomyces, Eubacterium, Lactobacillus, Propionibacterium, Neisseria,
      Veillonella, Bacteroides, Campylobacter, Capnocytophaga, Fusobacterium, Kingella,
      Porphyromonas and Prevotella species. There was no difference between the two
      groups except the significantly higher proportion of Kingella dentrificans
      isolated from group B sites. However, colonization of the gingival sulcus in
      these individuals by microbes that are normal flora of: skin (Peptostreptococcus
      prevotii and Propionibacterium granulosum) and gut (Eubacterium aerofaciens,
      Fusobacterium mortiferum and Fusobacterium varium) was detected. These findings
      appear to suggest that the major components of the subgingival microflora of
      shallow sites in previously head- and neck-irradiated individuals are similar to
      that of gingivitis sites in the normal population although they may contain
      bacterial or fungal species uncommon in normal subjects.

PMID- 9573816
TI  - Rapid isolation of chromosomal DNA from oral streptococci and polymerase chain
      reaction-oriented restriction fragment-length polymorphism analysis for genetic
      heterogeneity.
AB  - We have extensively modified the published method for the lysis of gram-positive
      bacteria to isolate chromosomal DNA from only 1 ml of oral streptococcal
      overnight culture. Cells were incubated with lysozyme and R Nase A in the
      presence of polyethylene glycol. After centrifugation, cells were lysed with
      sodium dodecyl sulfate and proteinase K. Following ethanol precipitation, sodium
      dodecyl sulfate solution was added to the residue, and the pellet was completely
      dispersed by incubating at 65 degrees C. The chromosome was purified by
      extraction over phenol and chloroform. Two regions corresponding to the ribosomal
      RNA (rrn) operon and the glucosyltransferase gene were amplified using the
      chromosome from Streptococcus mutans and Streptococcus sobrinus by polymerase
      chain reaction (PCR). Genetic heterogeneity was assessed by restriction fragment
      length polymorphism (PCR-RFLP). The PCR-RFLP analysis readily allowed us to
      subtype each strain, suggesting that the strategy presented here will provide a
      useful tool to verify epidemiological studies at the molecular level.

PMID- 9573817
TI  - Arbitrarily primed polymerase chain reaction fingerprinting for the genotypic
      identification of mutans streptococci from humans.
AB  - Determining whether two strains of bacteria are unique, identical or clonally
      related depends upon comparisons of phenotypic and/or genotypic traits.
      Individual isolates can then be grouped according to differences or similarities
      among those traits. One method of genotyping strains of bacteria is commonly
      referred to as chromosomal DNA fingerprinting. Previously, we generated
      chromosomal DNA fingerprints of mutans streptococci to study the transmission of
      this organism within families. Here, we developed and evaluated an arbitrarily
      primed polymerase chain reaction (AP-PCR) method for the genotypic
      characterization of mutans streptococci. Results were compared to those derived
      from the more conventional chromosomal DNA fingerprinting method. First, we
      showed that randomly selected clinical isolates displayed a unique banding
      profile by both methods; the mean similarity indices between DNA fragment
      patterns were 0.69 for chromosomal DNA fingerprinting and 0.74 for AP-PCR. This
      indicated that AP-PCR demonstrated less diversity than chromosomal DNA
      fingerprinting. Subsequently, we tested the agreement between chromosomal DNA
      fingerprinting and AP-PCR in determining genotypic similarities among 21 mutans
      streptococci strains obtained from 10 mother-child pairs, and 5 mutans
      streptococci strains from 5 fathers. The Kappa value for agreement was 0.88. We
      conclude that AP-PCR, which generates patterns of 8 to 12 amplicons, is capable
      of distinguishing strains of mutans streptococci among non-related individuals.
      Moreover, AP-PCR can discern both homogeneity and heterogeneity of mutans
      streptococci genotypes among mother and child pairs. Overall, we found that AP
      PCR gave results comparable to those of chromosomal DNA fingerprinting.

PMID- 9573818
TI  - Restriction fragment-length polymorphism analysis of 16S rDNA from oral
      asaccharolytic Eubacterium species amplified by polymerase chain reaction.
AB  - Restriction fragment-length polymorphism (RFLP) analysis of 16S rDNA amplified by
      polymerase chain reaction was used to generate restriction profiles of the type
      strains of oral asaccharolytic Eubacterium species, that is, Eubacterium brachy,
      Eubacterium exiguum, Eubacterium lentum, Eubacterium minutum, Eubacterium
      nodatum, Eubacterium saphenum, Eubacterium timidum and 33 asaccharolytic
      Eubacterium strains isolated from oral sites. The 16S rRNA gene sequences from
      isolated genomic DNA samples were amplified by polymerase chain reaction (PCR).
      PCR products were purified and characterized by single digestions with 7
      restriction endonucleases. Among the 7 endonucleases, HpaII was found to
      discriminate the respective reference strains. Twenty-three isolates, out of 33,
      were assigned to one of the reference species, on the basis of their restriction
      profiles by digestion with HpaII. The remaining 10 isolates could not be assigned
      to any of the established species and constituted 4 distinct groups, each of
      which may be a new species.

PMID- 9573819
TI  - Identification of bacterial species on or in crevicular epithelial cells from
      healthy and periodontally diseased patients using DNA-DNA hybridization.
AB  - The purpose of this investigation was to identify bacterial species present on or
      in crevicular epithelial cells in healthy and diseased sites using DNA probes. In
      order to achieve this aim, further improvements were made in the separation of
      unattached bacteria from those adherent to epithelial cells isolated from the
      human gingival crevice or periodontal pocket. Then the DNA probes were used to
      determine the prevalence of detectable DNA from 15 microbial species on or in
      crevicular epithelial cells. One sample was taken from a single subgingival site
      in each of 51 individuals ranging in age from 19 to 45 years. Samples were taken
      from 27 sites of clinically healthy subjects and 24 samples were taken from
      subjects having periodontally diseased sites. DNA-DNA hybridization indicated
      that a majority of epithelial cells from healthy sites (63%) were in contact with
      or harbored Streptococcus oralis. On the other hand, species such as Bacteroides
      forsythus, Prevotella intermedia, Capnocytophaga ochracea and Campylobacter
      rectus were more frequently detected in elevated numbers in periodontally
      diseased sites. Cluster analysis of the microbial profiles generally aggregated
      subjects with and without periodontitis into separate cluster groups. The cluster
      patterns suggest the possibility that microbial complexes will be, in part,
      determined by the receptors available on the epithelial cells.

PMID- 9573820
TI  - beta-Lactamase-producing strains in the species Prevotella intermedia and
      Prevotella nigrescens.
AB  - A total of 96 strains were collected that included laboratory strains and
      clinical isolates classified Prevotella intermedia sensu lato and the type
      strains of the species P. intermedia sensu stricto and Prevotella nigrescens.
      Susceptibility to amoxicillin and amoxicillin-clavulanic acid was determined by
      the Etest. PCR-DNA probe assays were used to speciate each strain as P.
      intermedia sensu stricto or P. nigrescens. By Etest, 71 strains (74%) were
      susceptible to both amoxicillin and amoxicillin-clavulanic acid with minimum
      inhibitory concentrations in the 0.016-0.064 microgram/ml range. In contrast,
      amoxicillin minimum inhibitory concentrations of 25 strains (26%) were in the
      range of 1.5-96 micrograms/ml with concomitant amoxicillin-clavulanic acid
      minimum inhibitory concentrations in the low range 0.016-0.38 microgram/ml,
      indicating a production of beta-lactamase as confirmed by nitrocefin tests. Of
      these beta-lactamase-producing strains, 20% (5/25) were identified as P.
      intermedia sensu stricto by the PCR-DNA probe assay and 72% (18/25) as P.
      nigrescens. Our results provide support for the major role of P. nigrescens in
      the failure of therapy using beta-lactam antibiotics.

PMID- 9573821
TI  - Differential activation of human neutrophils by Streptococcus mutans isolates
      from root surface lesions and caries-free and caries-active subjects.
AB  - Phagocytosis of bacterial pathogens is an important defense mechanism and may
      contribute to regulating Streptococcus mutans-induced dental caries, particularly
      at root surfaces. This study was undertaken to examine and compare differences in
      polymorphonuclear leukocyte or neutrophil activation by clinical isolates of S.
      mutans collected from the saliva of caries-free or caries-active individuals with
      S. mutans isolates from root surface lesions. S. mutans clinical isolates (5
      caries-free, 5 caries-active, 5 root caries isolates and a laboratory strain)
      were incubated with neutrophils in the presence of normal human serum and the
      luminol dependent chemiluminescence was measured for 1 h at 37 degrees C. Results
      indicated that the caries active and laboratory strains activated neutrophils
      equally. The mean integration stimulated by caries-free strains, however,
      displayed a 25-30% enhanced neutrophil activation over the caries-active and
      laboratory strains. In contrast, neutrophil activation by root caries strains of
      S. mutans was 45-50% lower than all other S. mutans strains, possibly suggesting
      a natural selection for S. mutans strains that can evade neutrophil recognition
      and subsequent phagocytosis. Stimulation of neutrophils with the cell wall and
      membrane surface component preparations indicated that extracts from all four
      groups activated neutrophils significantly. Again, caries-free preparations
      activated neutrophils significantly more than caries active, laboratory strain
      and root caries isolates. This selection may become more important on root
      surfaces due to increased exposure to crevicular fluid and neutrophils. The data
      provide evidence for the presence or onset of mechanisms or biological
      alterations in S. mutans developed to circumvent neutrophil recognition and/or
      phagocytosis, thus increasing S. mutans survival and colonization on tooth
      surfaces, resulting in an enhanced risk of dental caries, particularly at root
      surfaces.

PMID- 9573822
TI  - Characterization of a novel N-acetylneuraminic acid-specific Fusobacterium
      nucleatum PK1594 adhesin.
AB  - Fusobacterium nucleatum has been identified as significantly associated with
      sites with active periodontal disease and, as a group, the oral fusobacteria
      coaggregate with members of all oral bacteria genera tested. Monoclonal
      antibodies were prepared and used in conjunction with other potential inhibitors,
      such as simple sugars and amino acids, to characterize coaggregation
      interactions, of F. nucleatum PK1594. Four unique monoclonal antibodies, 5H11,
      14C7, 19F2 and 29C12, were obtained by their ability to inhibit coaggregation of
      F. nucleatum PK1594 with Actinomyces israelii PK16. They were also capable of
      inhibiting other coaggregations including Streptococcus oralis H1, S. oralis J22,
      Capnocytophaga ochracea ATCC33596, Prevotella denticola PK1277 and Prevotella
      intermedia PK1511. All of these interactions were completely inhibited by N
      acetylneuraminic acid. Neither N-acetylneuraminic acid nor monoclonal antibody
      5H11 had any inhibitory effect on other F. nucleatum PK1594 interactions,
      including all galactose-inhibitable coaggregations. The results indicate that F.
      nucleatum PK1594 expresses upon its surface a distinct type of adhesin that
      mediates coaggregation interactions that are inhibited by N-acetylneuraminic
      acid.

PMID- 9573823
TI  - Helicobacter pylori adheres selectively to Fusobacterium spp.
AB  - Helicobacter pylori strains ATCC 43504 and ATCC 43629 were tested for their
      ability to coaggregate with 79 strains of bacteria representing 16 genera. All
      except two of the strains were of human origin, and most of the strains were
      isolated from the oral cavity. The helicobacters failed to coaggregate with all
      strains except the fusobacteria. Several coaggregations were partially or
      completely inhibited by lactose. Strong coaggregation was seen with each of four
      subspecies of Fusobacterium nucleatum and with Fusobacterium periodonticum ATCC
      33693, all of human dental plaque origin. In contrast, the helicobacters failed
      to coaggregate with non-plaque isolates, Fusobacterium mortiferum ATCC 25557 and
      Fusobacterium ulcerans ATCC 49185. Heat treatment of the fusobacteria inactivated
      their ability to coaggregate, whereas heating of the Helicobacter partners had no
      effect, suggesting the presence of an adhesin on the fusobacteria and a
      corresponding receptor on the helicobacters. The potential ability of H. pylori
      to colonize the oral cavity by adhering selectively to the ubiquitous
      fusobacteria gives credence to the possibility that dental plaque may serve as a
      reservoir for this pathogen outside of the stomach.

PMID- 9573824
TI  - Cross-reactivity of specific antibodies directed to heat shock proteins from
      periodontopathogenic bacteria and of human origin [corrected].
AB  - This study describes the immunological characterization of two different classes
      of heat shock proteins isolated from periodontopathogenic bacteria. Analysis of
      the N-terminal amino acid sequence of a 74-kDa protein from Bacteroides forsythus
      showed a high degree of homology with the DnaK protein from Escherichia coli.
      However, this heat shock protein from B. forsythus reacted very weakly with a
      commercial anti-DnaK polyclonal antibody by dot-blotting. GroEL-like proteins
      isolated from Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and
      B. forsythus showed a high degree of homology of their N-terminal amino acid
      sequences. In general, polyclonal antibodies raised against each GroEL-like
      protein showed a high level of cross-reactivity. The cross-reactivity of
      antibodies to bacterial DnaK-like proteins was much more limited. Our findings
      suggest that DnaK- and GroEL-like proteins from periodontal pathogens are well
      conserved and that the GroEL-like proteins resemble each other more closely.

PMID- 9573825
TI  - Cystatin D, a natural salivary cysteine protease inhibitor, inhibits coronavirus
      replication at its physiologic concentration.
AB  - This study was conducted to examine the effect of cystatin D, a newly discovered
      salivary cysteine protease inhibitor, on human coronavirus replication. When MRC
      5, human diploid lung cells, were incubated with dilutions of recombinant human
      cystatin D from 0.65-10 microM for 1 h prior to, during and after infection with
      coronavirus OC43 and 229e strains, a decrease in virus yield was observed
      resulting in an IC50 of 0.8 microM for both virus strains. This dose is within
      the normal concentration range of cystatin D, 0.12-1.9 microM found in saliva.
      When a single dose, 2.5 microM, was applied, cystatin inhibition of release of
      virus progeny was not overcome until three days post infection whereas inhibition
      by leupeptin, a serine and cysteine protease inhibitor, was completely abrogated
      by two days. When cellular toxicity was measured by 3H-thymidine uptake, cystatin
      D did not markedly affect cell proliferation below a 10 microM dose. The results
      demonstrate that cystatin D is a potent inhibitor of coronavirus replication.

PMID- 9573826
TI  - Prevalence of Peptostreptococcus micros morphotypes in patients with adult
      periodontitis.
AB  - The prevalence of the smooth and rough colonial morphotypes of Peptostreptococcus
      micros was examined with culture technique in 123 patients with adult
      periodontitis (age 24-68 years). Of all subgingival samples, 91% contained the
      smooth morphotype of P. micros. The smooth morphotype constituted a mean
      percentage of the total anaerobic viable biota of 6.0%, with a range of 0.02
      35.7%. Of these samples, 49% contained colonies of the rough morphotype as well,
      with a mean percentage of the total anaerobic viable biota of 2.3% (range 0.01
      16.2%). None of the samples contained only the rough morphotype. The total
      percentage of P. micros varied from 0.02-35.71% with a mean of 7.2%. No
      correlation was found between the prevalence of both morphotypes of P. micros and
      the age of the subjects or with loss of attachment or pocket depth.

PMID- 9573827
TI  - Women in dentistry.

PMID- 9573828
TI  - Advances in home therapy for gingivitis--revolution or evolution?
AB  - The daily use of toothpaste offers the opportunity for additional therapeutic
      benefits beyond caries control. The dental professional must be prepared to
      assist patients in making informed choices about these products to maximize their
      benefits as a supplement to mechanical oral hygiene. Dentifrices containing
      chemotherapeutic agents that are successful in controlling gingivitis, when
      combined with mechanical therapy, have the potential to improve oral health.
      However, the published clinical studies on some of these products do not always
      present a consistent picture with regard to absolute or relative efficacy. In
      this article, the clinical studies on dentifrices containing sodium
      bicarbonate/hydrogen peroxide, chlorhexidine, triclosan, and stannous fluoride
      are reviewed. In addition, suggestions for the analysis of these types of studies
      by practitioners are presented. Ultimately, it is the responsibility of the
      dental professional to provide monitoring and guidance to assist patients in
      making informed decisions about oral health care product use.

PMID- 9573829
TI  - Placement protocol for an anterior fiber-reinforced composite restoration.
AB  - The new classification of metal-free restorative materials provides the clinician
      with a durable, flexible, and aesthetic laboratory-fabricated alternative to
      conventional porcelain-fused-to-metal (PFM) full-coverage crowns, inlay and onlay
      restorations, and single pontic bridges. With exceptional physical and optical
      characteristics, restorations fabricated utilizing the new ceramic optimized
      polymer (Ceromer) (Targis, Ivoclar Williams, Amherst, NY) and fiber-reinforced
      composite (FRC) framework (Vectris, Ivoclar Williams, Amherst, NY) materials can
      also be utilized predictably in the anterior segment. The success of metal-free
      restorations can be achieved by following conventional prosthodontic principles
      for preparation, cementation, and finishing. This article demonstrates the
      appropriate treatment protocol in order to achieve aesthetically acceptable and
      durable anterior results utilizing a metal-free restorative system for "Maryland
      like" bridge restorations.

PMID- 9573830
TI  - A new system for posterior restorations: a combination of ceramic optimized
      polymer and fiber-reinforced composite.
AB  - Due to the need for increased strength characteristics and enhanced aesthetic
      expectations of the patients, metal-free, aesthetic restorative systems for the
      anterior and posterior dentition are currently available. A new "space-age"
      restorative material has been developed that is a combination of a ceramic
      optimized polymer (Ceromer) (Targis/Vectris, Ivoclar Williams, Amherst, NY) and a
      fiber-reinforced composite framework material. The purpose of this article is to
      discuss the qualities that render this material particularly suitable for a
      variety of indications, including laboratory-fabricated restorations for the
      stress-bearing posterior regions. The material lends itself to diversification.
      Its indication for inlays, onlays, full-coverage crown restorations, and
      conservative single pontic inlay bridges is presented.

PMID- 9573831
TI  - Clinical efficacy of the Nd:YAG laser for combination periodontitis therapy.
AB  - Recent results of a limited clinical trial suggest that mechanical root scaling
      and root planing therapy alone may not be the most effective mode of treatment
      for patients affected by moderate to severe adult periodontitis. However, scaling
      and planing combined with laser therapy utilizing a low-powered pulsed Nd:YAG
      laser have been shown to be successful in the elimination of the bacteria
      commonly associated with the development of this oral condition. The double
      blind, split mouth design study involved 10 human subjects randomly assigned to
      one of three treatments: 1) scaling and root planing alone, 2) dental laser plus
      scaling and root planing, and 3) control only. This article presents the clinical
      results of the trial, which suggest that laser therapy is a viable adjunct to
      local, nonsurgical therapy such as scaling and planing.

PMID- 9573832
TI  - Clinical advances of the pulsed Nd:YAG laser in periodontal therapy.
AB  - Since the Nd:YAG laser was first developed in the 1960s, its spectrum of
      capabilities has continued to expand in the medical field. In dentistry,
      treatment of both hard and soft tissue has been affected, with the most
      noticeable change occurring in the management of periodontal disease. The
      learning objective of this article is to review the utilization of the pulsed
      Nd:YAG laser (American Dental Technologies, Southfield, MI) in the management of
      periodontal disease. Cases are presented to document the clinical aspects, and
      directions of future research are indicated.

PMID- 9573833
TI  - Oral lichen planus: parameters affecting accurate diagnosis and effective
      management.
AB  - Oral lichen planus is one of the most common mucosal diseases that require
      management by the dental practitioner. The gingival presentation of this disease
      can be particularly problematic. Accurate diagnosis is of paramount importance
      for effective management, and tissue specimens are often required to distinguish
      this disease from other vesiculo-ulcerative diseases. The lichen planus patient
      can generally be managed with topical steroids. The use of antibiotics may be an
      important adjunctive consideration for patients with a concurrent significant
      periodontal condition. The possibility of carcinoma arising in lichen planus
      lesions is addressed. The learning objective of this article is to define
      specific parameters that contribute to the definitive diagnosis in order to
      promote objective, rather than empirical, treatment and to delineate specific
      points to address in patient education.

PMID- 9573834
TI  - Preservation of a fractured mandibular central incisor.

PMID- 9573835
TI  - Oral candidiasis: clinical manifestations, diagnosis, and treatment.
AB  - Oral candidiasis (candidosis) is an infection with multiple manifestations. To
      prevent prolongation of undiagnosed cases, it is essential that the dental
      clinicians have an understanding of the etiology, pathogenesis, and treatment of
      this disease. The learning objective of this article is the identification of the
      various clinical features of candidiasis. The underlying causes of oral
      candidiasis include antibiotic therapy, poor denture hygiene, xerostomia, immune
      deficiencies, diabetes, and some less common conditions. Candidal infection may
      be superimposed on other mucosal diseases and may disguise the underlying
      disease. The diagnosis is established using clinical appearance and patient
      history, and it may require diagnostic tests. A significant segment of the
      population carries intraoral Candida, without any symptoms of infection,
      complicating the use of diagnostic tests.

PMID- 9573836
TI  - Local anesthetics and vasoconstrictors: myths and facts.

PMID- 9573837
TI  - Bulimia nervosa: dental perspectives.
AB  - Bulimia nervosa and bulimic behavior are among the most common eating disorders,
      affecting up to 13% of female college students. Most health professionals are
      aware of the compulsive overeating, self-induced vomiting, and laxative abuse
      associated with this disease; yet, only a small proportion of affected patients
      are ever diagnosed, generally only after years of abuse. Since the dental changes
      observed in most bulimics are recognizable and usually undeniable, the clinician
      should be aware of the oral and maxillofacial changes of this disease in order to
      arrive at an early diagnosis. Without successful treatment, an estimated 1 in 300
      bulimic cases will have a fatal outcome. Even with treatment, one-third of
      affected individuals suffer early relapse and half of them do not consider
      themselves cured after 5 years of psychologic therapy. The learning objective of
      this article is to discuss the dental and psychologic features of this disorder,
      with focus on the differential diagnosis and treatment of the oral
      manifestations.

PMID- 9573838
TI  - Indirect trauma to the temporomandibular joints.

PMID- 9573839
TI  - Viral infections of the oral mucosa in children: a clinical review.
AB  - The oral cavity is a microcosm of the world around us, exposed to a variety of
      microorganisms present in the local environment. Some of these microorganisms
      establish a permanent presence in the oral tissues, which serve as a suitable
      growth medium. These locations include soft and hard tissue, areas of high and
      low oxygen content, flowing secretions and dryness, and flat or grooved surfaces.
      Most of the normal oral flora does not cause disease; some even provide a
      protective benefit. However, occasionally one or more groups become pathologic,
      producing a disease that may have serious consequences for the host. Many of the
      pathologic microorganisms are viruses, and children are particularly prone to
      such infections, since their immune systems are still in the development stage.
      The learning objective of this article is to review the viral infections of the
      oral mucosa in children, including varicella, herpes zoster, mononucleosis, and
      herpangina.

PMID- 9573840
TI  - Aesthetic all-ceramic restorations: the internal live stain technique.
AB  - The utilization of porcelain as a restorative material began a new era in
      aesthetic dentistry. By today's standards, the early porcelains were rather
      primitive and of low value. However, the potential of all-ceramic material for
      aesthetic dentistry was recognized, and various modifications and enhancements
      followed to render the material applicable for dental restorations. The learning
      objective of this article is to present the history of development, the
      principles, and the laboratory fabrication of ceramic restorations utilizing the
      Internal Live Stain Technique. The technique uses stains with all-ceramic
      material to achieve the optimal simulation of natural dentition. While
      replicating the optical properties inherent in the natural dentition, the
      application of the stain improves the physical characteristics of the all-ceramic
      material. The general principles of the first and second applications are
      disclosed, followed by presentation of two clinical cases--all-ceramic crown and
      laminate veneer restorations in the maxillary anterior segment.

PMID- 9573841
TI  - The use of a pre-impregnated, fiber-reinforced composite in the fabrication of a
      periodontal splint: a preliminary report.

PMID- 9573842
TI  - Fibromyalgia.

PMID- 9573843
TI  - The sinus lift graft: basic technique and variations.
AB  - Following an early controversy concerning its efficacy, the sinus lift and graft
      technique is now considered to be a state-of-the-art surgery. In 1975, Tatum
      introduced the technique that increased maxillary bone height by placing graft
      material under the maxillary sinus and Schneiderian membrane; by the early 1990s,
      a modification of Tatum's original technique had become a standard procedure.
      This article describes and illustrates three variations of the basic sinus lift
      surgery and graft operation--the hinge osteotomy, the elevated osteotomy, and the
      complete osteotomy. Additional considerations affecting the surgical outcome are
      also discussed as is the management of possible complications. The learning
      objective of this article is to obtain up-to-date information regarding the basic
      technique and variations of the sinus lift procedure to the general practitioner
      as well as the specialist.

PMID- 9573844
TI  - Rest in peace, G. V. Black: Part II.

PMID- 9573845
TI  - Single-tooth implant-supported restorations in the anterior maxilla.
AB  - With the development of advanced surgical techniques, implants can now be
      utilized in a variety of applications, including replacement of a single tooth.
      The form of an artificial restoration is determined by the existing tooth
      morphology and periodontal architecture; when placing single-tooth implants, the
      original structure of the tooth and periodontium must be recreated.
      Osseointegrated single-tooth implants have a success rate that is comparable to
      that of implant-supported prostheses in totally edentulous patients; a 98.5%
      success rate has been reported following 3 years in situ. The learning objective
      of this article is to gain an understanding of pretreatment guidelines, such as
      soft tissue considerations, bone dimension, root morphology, and site preparation
      with osteotomes for single-tooth implant placement. The review also includes the
      discussion of the placement of single-tooth implants, flap design, prosthetic
      considerations, and the final restoration. Two case reports are presented to
      document and illustrate the clinical procedure.

PMID- 9573846
TI  - A case report of compromise.

PMID- 9573847
TI  - A combination porcelain/fiber-reinforced composite bridge: a case report.
AB  - In the search for an optimal treatment to restore the aesthetically prominent
      maxillary anterior dentition, new materials are continually introduced. The
      attention of the patients has shifted from function to aesthetics,
      biocompatibility of the materials utilized, and conservative preparation of teeth
      to be restored. To fulfill patient expectations, an advanced treatment modality
      has recently been developed. It combines porcelain with composite resin, thereby
      integrating the strength and resilience of composite resin with the aesthetic
      advantages of porcelain. To achieve this combination, bundles of fibers are
      impregnated with resin in the fabrication phase of the material. The learning
      objective of this article is to briefly review the past methods of fabricating a
      3-unit prosthesis in the maxillary anterior region and describe the recently
      introduced treatment alternative.

PMID- 9573848
TI  - Treatment classifications and sequencing for postextraction implant therapy: a
      review.
AB  - Dental implantology has become an acceptable and effective treatment modality for
      totally and partially edentate alveolar arches. When teeth are extracted due to
      pathology or trauma, bone and soft tissue resorption often occurs. Either an
      immediate implant placement must be performed or a more traditional treatment
      plan must be determined; teeth for extraction or incorporation into the overall
      treatment scheme must also be selected. Selection of the implant site must
      reflect the mesiodistal, buccolingual, and apicocoronal dimensions. The
      responsibility of the implant team is to establish a correct diagnosis, evaluate
      clinical parameters, and design a comprehensive treatment plan, selecting the
      optimal time for implant placement. The learning objective of this article is to
      review three classifications of extraction sites and the time sequences of
      surgical protocols to implant placement following extraction.

PMID- 9573849
TI  - Aesthetics at what cost?

PMID- 9573850
TI  - Mandibular tori as a source for onlay bone graft augmentation: a surgical
      procedure.
AB  - Conventional dentistry has provided acceptable treatment alternatives for the
      partially or fully edentulous patient for decades. Recent innovations have
      provided clinicians with an assortment of new techniques to restore the function
      of these patients. Established treatment alternatives have been significantly
      enhanced, resulting in increased acceptance of predictable dental implant
      restorations. However, implant dentistry cannot be successfully utilized in all
      edentulous patients, and augmentation measures are often necessary to enhance the
      alveolar bone, requiring autogenous donor sites. While bone tissue has been
      harvested from numerous sites, the mandibular tori may provide sufficient graft
      material. The teaching objective of this article is to describe a clinical
      implant placement procedure, utilizing bilateral tori as the donor sites of the
      autogenous grafting material. A clinical case is utilized to document the tori
      removal and the augmentation procedures.

PMID- 9573851
TI  - Aesthetic anterior restorations in medically compromised, low-income patients.

PMID- 9573852
TI  - Aesthetic ridge and extraction site augmentation for anterior implant placement
      without barrier membrane.
AB  - Augmentation of the alveolar ridge to facilitate implant placement in a single
      tooth extraction site or a completely edentulous arch is currently a well
      accepted and routinely performed therapeutic procedure. This article describes a
      method for augmenting extraction sites and ridges, without primary closure or the
      use of barrier membranes over bone grafts. The technique retains or enhances
      gingival architecture while creating bone for placement of an implant in the most
      optimal position. The tooth is extracted, demineralized freeze-dried bone
      allograft or another augmentation material of choice is placed, and a provisional
      mucoadhesion partial denture is delivered. When the implant is uncovered and the
      healing abutment is placed, a flap design is utilized to create papillae and
      proper labial contour. The learning objective is familiarity with this technique,
      which is particularly useful for maxillary anterior implant placement. A case
      report is used to document the clinical procedure.

PMID- 9573853
TI  - Prosthetic considerations in the fabrication of surgical stents for implant
      placement.
AB  - The utilization of surgical stents/templates for implant placement is of
      significant importance to the success of the definitive prosthesis. However,
      major conceptual differences exist between surgical stents designed for implant
      supported crowns and bridges and those designed for implant overdentures. In
      addition, various types of surgical stents exist within each group. In either
      case, optimizing the prosthetic result by customization of the stent should be a
      major consideration in the fabrication process. The design of the stent must
      account for several treatment conditions, including position of the implant, the
      tissue present, and the anticipated prosthesis. The teaching objective of this
      article is to present the prosthetic considerations in the fabrication and
      customization of surgical stents. The article compares the two groups and offers
      specific guidelines for the fabrication of surgical stents for the various types
      of restorations within each group.

PMID- 9573854
TI  - Patient premedication in the prevention of dental-procedure-induced endocarditis.

PMID- 9573855
TI  - Simultaneous hard and soft tissue augmentation for implant-supported single-tooth
      restorations.
AB  - The replication of nature in the rehabilitation of a single missing anterior
      tooth is primarily a surgical challenge, as hard and soft tissue deficiencies
      compromise the achievement of functional and aesthetic implant-supported
      restorations. Bone defects can be treated using guided bone regeneration (GBR),
      with or without bone graft materials. The successful application of the GBR
      technique has been documented in several experimental and clinical studies; the
      primary challenge associated with single tooth replacement is the creation of an
      adequate soft tissue recipient site. However, the increased morbidity and
      prolonged healing period involved in performing hard and soft tissue grafting
      procedures in two consecutive appointments do not achieve patient expectations.
      The learning objective of this article is to master a single-tooth replacement
      technique that allows surgical treatment of bony and soft tissue deficiencies in
      a single procedure, during either an immediate or delayed implant placement.

PMID- 9573856
TI  - Alumina-zirconia machinable abutments for implant-supported single-tooth anterior
      crowns.
AB  - Innovative materials and application techniques are constantly being developed in
      the ongoing search for improved restorations. This article describes a new
      material and the fabrication process of aesthetic machinable ceramic anterior
      implant abutments. The ceramic material utilized is a mixture of alumina
      (aluminum oxide) and ceria (cerium oxide) with partially stabilized zirconia
      (zirconium oxide). The initial core material is a cylinder with a 9-mm diameter
      and a 15-mm height, obtained by ceramic injection and presintering processes. The
      resultant alumina-zirconia core is porous and readily machinable. It is secured
      to the analog, and its design is customized by machining the abutment to suit the
      particular clinical circumstances. The machining is followed by glass
      infiltration, and the crown is finalized. The learning objective of this article
      is to gain a basic knowledge of the fabrication and clinical application of the
      custom machinable abutments.

PMID- 9573857
TI  - Pain management. Biofeedback and relaxation therapy.

PMID- 9573858
TI  - Fixed temporization and bone-augmented ridge stabilization with transitional
      implants.
AB  - Utilization of dental implants in full-mouth restorations is now a well-accepted
      treatment modality, with numerous modifications and implant systems documented in
      the literature. The efficacy of the treatment procedure generally requires an
      extended postplacement healing period prior to loading the implant fixture with
      the stress of mastication. Until recently, clinicians have not been able to
      address patient comfort requirements during the healing period. The teaching
      objective of this article is to present and evaluate a transitional implant
      system used to provide function during the healing phase. The system consists of
      thin titanium transitional implants and a three-component overdenture that is
      intended to absorb the pressure during function and protect the augmented implant
      site and the definitive implant fixtures from the stress of immediate loading.
      Treatment objectives for the transitional and definitive implants are made during
      the initial treatment planning. Three cases are presented to document and
      illustrate the clinical procedure.

PMID- 9573859
TI  - The double guidance concept.
AB  - The function in implant-supported restorations is now predictably achieved, and
      the emphasis has shifted to aesthetics. Simultaneously with this change in focus,
      the direction toward prosthetic restorations as the ultimate objective of implant
      procedures has evolved. The anticipated prosthesis now dictates the placement and
      angulation of the implant, thereby improving the function and, above all, the
      aesthetics of the final result. The purpose of this article is to discuss the
      concept of guidance for optimized management of hard and soft tissues, during the
      surgical procedure and during tissue healing. Particular attention is given to
      the reformation of the papillae.

PMID- 9573860
TI  - Glass-ionomer cements in restorative dentistry.
AB  - This article reviews the current status and future prospects for glass-ionomer
      materials. These materials are of two chemical types: the older, self-hardening
      cements, which set by an acid-base neutralization reaction to give relatively
      brittle materials; and the newer, resin-modified cements, which set partly by
      polymerization and partly by neutralization. Compared with the self-hardening
      cements, the latter materials have improved esthetics, improved resistance to
      moisture, and greater toughness. Both types of glass-ionomer cement bond well to
      enamel and dentin and release a clinically useful amount of fluoride. They have
      been used in a variety of applications: as liners or bases, for luting of
      stainless steel crowns, for Class V restorations in permanent teeth, and for
      Class II and Class III restorations in primary teeth. The resin-modified glass
      ionomers are particularly promising for these latter uses, although it is too
      early to be sure whether their long-term durability is sufficient. Self-hardening
      glass-ionomer materials are likely to retain specific niches of clinical
      application, including in their metal-reinforced and cermet-containing forms.

PMID- 9573863
TI  - Potential of gingival connective tissue to induce keratinization of an alveolar
      mucosal flap: a long-term histologic and clinical assessment. Case report.
AB  - A maxillary canine and premolar showed a 3.0- to 4.0-mm-deep and 3.0- to 4.0-mm
      wide recession defect with 2.0- to 3.0-mm zone of attached gingiva. The denuded
      root surfaces were covered with nonkeratinized alveolar mucosa in a slightly
      modified bridge flap technique. The coronal displacement of a nonkeratinized
      alveolar mucosal flap onto a bed of collagenous gingival connective tissue
      resulted in the development of keratinized epithelium in the previously
      nonkeratinized mucosa. This was caused by the inductive stimuli of the underlying
      tissue and observed in the 6-month specimen. The alveolar mucosa displayed its
      transformed epithelial structural pattern only in segments, achieving full
      differentiation of its basal complex over a 10-year period, as demonstrated
      clinically and histologically.

PMID- 9573862
TI  - Effect of glutaraldehyde cold sterilants on light transmission of curing tips.
AB  - This research examined the effect of immersion in glutaraldehyde-based cold
      sterilizing solutions on the ability of light-curing tips to transmit a
      standardized light intensity. Five commercial cold sterilizing solutions were
      selected, based on their classification: neutral (Cetylcide-G, 3.2%), acidic
      (Banicide, 2.0%), or alkaline (Cidex Plus, 2.5%; Cidex 7, 3.4%; and Sporicidin,
      0.5%). Distilled water was used as the control. The light intensity transmitted
      through 24, 8-mm-diameter curing tips of similar type was determined by applying
      a standardized intensity (500 m W/cm2). Three tips were placed into each type of
      solution. The percentage of preimmersion intensity was determined at periodic
      intervals until all tips had received a total of 1,000 hours of immersion. After
      1,000 hours' immersion, light transmission decreased significantly more in tips
      subjected to Cidex 7 than in tips subjected to all other treatments, which were
      all equivalent to the water control (an average increase of 1.5% over
      preimmersion values). The decrease in intensity seen with Cidex 7 averaged 49%
      and could not be totally recovered after use of conventional tip-polishing
      methods. Reduction in light levels could not be correlated with the pH of the
      sterilizing solutions.

PMID- 9573861
TI  - Methods used in dentin bonding tests: an analysis of 50 investigations on bond
      strength.
AB  - Researchers have carried out a variety of investigations to determine the
      properties of available dentin bonding systems. The test methods and variables
      used in 50 published investigations of bond strength were analyzed. Among the
      studies analyzed, shear tests predominated, being used in 80% of the studies;
      dentin from human molar teeth was used most often (in 88% of investigations); and
      the most prevalent time of testing was 24 hours postcuring. However, a number of
      potential variables were not recorded in a high proportion of articles, among
      these the film thickness, the type of dentin tested, and the surface condition
      (moist or dry). The mode of failure was recorded in only 42% of the
      investigations assessed. It was found that there is little standardization of
      test methods in studies of dentin bond strength and that a number of variables
      are often either not recorded or reported.

PMID- 9573864
TI  - A split-shank prefabricated post system: a critical multidisciplinary review.
AB  - A multidisciplinary panel of senior academics and practitioners has evaluated a
      system of prefabricated threaded split-shank posts (Flexi-Post/Flexi-Flange) from
      published research and their own clinical use. These posts have been compared
      with requirements of an ideal post system in relation to clinical use, stress
      effects, stress distribution, retention, loosening and displacement, provision
      for cores, and biocompatibility. The purpose was to provide this critical review
      to allow interested clinicians to compare this novel design to other available
      post systems.

PMID- 9573865
TI  - Tuberculosis of the oral cavity: a case report.
AB  - Tuberculosis of the oral mucosa was associated with pulmonary tuberculosis in a
      38-year-old white man. The patient presented with multiple oral ulcerations with
      an irregular periphery and a granular vegetative fundus. The oral lesions
      antedated the findings of primary pulmonary tuberculosis, and the diagnosis was
      initially established histologically. Through the differential diagnosis of oral
      ulcerations, the dentist can play a role in the early detection of tuberculosis.

PMID- 9573866
TI  - Rieger's syndrome: a case report.
AB  - Rieger's syndrome is a rare autosomal-dominant disorder characterized by dental,
      ocular, and periumbilical abnormalities. Essential ocular features include
      goniodysgenesis, which leads to increased intraocular pressure and subsequent
      glaucoma and visual loss. Dental findings include midfacial hypoplasia and the
      absence of primary and permanent incisors and second premolars. Comprehensive
      preventive dental care in the form of fluorides and sealants is required,
      especially in patients with severe hypodontia, to increase the resistance of the
      remaining teeth to dental caries. This article describes a case of Rieger's
      syndrome in a 9-year-old child and emphasizes the need for comprehensive oral
      rehabilitation.

PMID- 9573867
TI  - Heterotopia of the mandibular third molar: a case report.
AB  - A rare finding of unilateral heterotopia of a mandibular third molar was most
      probably caused by primary and total dislocation of the tooth base. Other
      possible causative factors, such as a lack of space between the mandibular second
      molar and the mandibular ramus or a disproportion between the base and the
      direction of growth of the third molar, have been considered in similar cases
      reported in the literature.

PMID- 9573869
TI  - Paediatric life support. New resuscitation guidelines.

PMID- 9573868
TI  - In vitro marginal leakage around Class II resin composite restorations with glass
      ceramic inserts.
AB  - The aim of the study was to evaluate in vitro the marginal seal in Class II resin
      composite restorations reinforced with glass-ceramic inserts. Forty Class II
      cavities, with the gingival margins located at the cementoenamel junction, were
      restored with Palfique Estelite light-cured resin composite and one of two
      different bonding agents, All Bond 2 and Tokuso Light Bond, with or without the
      inclusion of glass-ceramic inserts. The extent of dye penetration along the tooth
      restoration interface was measured under an optical microscope. The marginal seal
      of composite restorations placed with All Bond 2 was significantly better than
      that of restorations placed with Tokuso Light Bond. There was significantly less
      microleakage in All Bond 2 restorations without glass-ceramic inserts than in All
      Bond 2 restorations containing glass-ceramic inserts. No significant difference
      in marginal seal was demonstrated between Tokuso Light Bond restorations with
      glass-ceramic inserts and those without inserts.

PMID- 9573870
TI  - Unbiased quantitative testing of conventional orthodontic beliefs.
AB  - This study used a preexisting database to test in hypothesis from the
      appropriateness of some common orthodontic beliefs concerning upper first molar
      displacement and changes in facial morphology associated with conventional full
      bonded/banded treatment in growing subjects. In an initial pass, the author used
      data from a stratified random sample of 48 subjects drawn retrospectively from
      the practice of a single, experienced orthodontist. This sample consisted of 4
      subgroups of 12 subjects each: Class I nonextraction, Class I extraction, Class
      II nonextraction, and Class II extraction. The findings indicate that, relative
      to the facial profile, chin point did not, on average, displace anteriorly during
      treatment, either overall or in any subgroup. Relative to the facial profile,
      Point A became significantly less prominent during treatment, both overall and in
      each subgroup. The best estimate of the mean displacement of the upper molar cusp
      relative to superimposition on Anterior Cranial Base was in the mesial direction
      in each of the four subgroups. In only one extraction subject out of 24 did the
      cusp appear to be displaced distally. Mesial molar cusp displacement was
      significantly greater in the Class II extraction subgroup than in the Class II
      nonextraction subgroup. Relative to superimposition on anatomical "best fit" of
      maxillary structures, the findings for molar cusp displacement were similar, but
      even more dramatic. Mean mesial migration was highly significant in both the
      Class II nonextraction and Class II extraction subgroups. In no subject in the
      entire sample was distal displacement noted relative to this superimposition.
      Mean increase in anterior Total Face Height was significantly greater in the
      Class II extraction subgroup than in the Class II nonextraction subgroup. (This
      finding was contrary to the author's original expectation.) The generalizability
      of the findings from the initial pass to other treated growing subjects was then
      assessed by retesting modified hypotheses against a second database stored sample
      that earlier had been drawn randomly from two other orthodontic practices. The
      implications of the author's study strategy to the design of future shared
      digital databases is discussed briefly.

PMID- 9573871
TI  - Hyperefficient orthodontic treatment using tandem mechanics.
AB  - This article presents an advanced and efficient noncompliance method of therapy
      referred to as tandem treatment. Tandem treatment was devised to harness the
      predictable orthodontic and orthopedic responses elicited by two proven fixed
      Class II correction devices, the pendulum and Herbst appliances. Tandem treatment
      involves two separate actions to resolve certain types of Class II malocclusions.
      First, the upper arch is expanded and the upper molars moved distally into a
      Class I relation. The pendulum appliance uses palatal and tooth-borne anchorage
      to move the upper molars distally. The pendulum is followed by a simplified
      version of the fixed Herbst appliance, which serves as anchorage to retract the
      remainder of the maxillary teeth to previously Class I positioned molars. This
      tandem of "pendex" appliance and fixed anchorage Herbst appliance has the ability
      to greatly improve treatment efficiency when used in appropriately selected
      patients. A case report is used to illustrate the treatment protocol.

PMID- 9573872
TI  - A strategy for nonextraction Class II treatment.
AB  - Class II nonextraction treatment, which commonly includes distal movement of the
      maxillary molars to correct the molar relationship, most often can be successful
      when treatment is started in the late-mixed dentition stage of development. At
      least two factors contribute to this success. One is that the molars can be
      distalized routinely at this age. The second is that the "E" space is available
      and can be used either to help correct the molar relationship or to resolve any
      crowding that may exist. This article describes and illustrates the treatment of
      a late mixed-dentition patient with this type of Class II nonextraction treatment
      that includes distal movement of the maxillary molars with a 100 g NiTi coil
      system and the maintenance of the "E" space with a lip bumper.

PMID- 9573873
TI  - Functional appliance therapy with the Bionator.
AB  - Since the early 20th century, functional appliance therapy has been a significant
      part of orthodontic treatment, especially in Europe, where functional appliances
      have been used to treat many malocclusions, including some skeletal
      discrepancies. Although the success of functional appliance therapy as reported
      in numerous short-term studies from 1930 to 1975 led to an euphoric acceptance of
      this method, the few long-term studies, especially those comparing treated with
      untreated homogeneous control groups, indicated that the specific skeletal and
      dentoalveolar effects depended on the individual growth period and pattern of the
      patient. In this article, a specific functional appliance, the Bionator, is
      presented. Long-term follow-up studies provide indications for its use. At the
      present time, functional orthopedic appliance therapy has a more limited but well
      defined place in our therapeutic approach. The type and character of the
      malocclusion determines the indications and contraindications of the functional
      appliance. Scientific and clinical experience has shown the importance of a
      differential diagnosis for each patient, which integrates etiology and
      morphogenesis in the individual treatment objectives for special skeletal,
      dentoalveolar, and functional regions. Individualization in the construction of
      the appliance, taking the above-mentioned factors into consideration, is
      essential for optimal clinical results.

PMID- 9573874
TI  - An evaluation of two-phase treatment with the Herbst appliance and preadjusted
      edgewise therapy.
AB  - The purpose of this study was to evaluate the skeletal and dentoalveolar changes
      occurring during two-phase orthodontic treatment. A cephalometric study of Class
      II correction was carried out in 40 subjects (20 females, 20 males) who had been
      treated with the acrylic-splint Herbst appliance immediately followed by a second
      phase of preadjusted edgewise therapy. The average age at the start of Herbst
      therapy was 12.5 +/- 0.8 years for females and 13.6 +/- 1.2 years for males.
      Descriptive cephalometric data were compared with the normative values derived
      from the University of Michigan Elementary and Secondary School Growth Study.
      Control values were generated for each of the 40 Herbst patients based on gender,
      initial age, and duration of treatment. The results of this study indicate that
      the Class II correction achieved during Phase I treatment with Herbst appliance
      was due mainly to an increase in mandibular length, as well as distal movement of
      the maxillary molars and mesial movement of the mandibular molars and incisors.
      The accelerated mandibular growth rate observed during Herbst therapy was
      followed by a diminished growth rate during the edgewise phase that was less than
      control values. The overall increase in mandibular length was slight
      (approximately 1 mm), but significantly greater than control data for the whole
      group and the male subgroup; however, it was not significantly different between
      the treatment group and control data in the female subgroup. There were no
      significant treatment effects on lower anterior facial height and the mandibular
      plane angle at the end of either phase of treatment. The skeletal changes
      contributed to 55% of the molar correction during the Herbst therapy, whereas at
      the end of the second phase of treatment, skeletal change accounted for 80%.
      Significant anteroposterior dentoalveolar rebound was seen during the edgewise
      phase.

PMID- 9573875
TI  - Growth and the Class II patient: rendering unto Caesar.
AB  - In the context of Class II treatment, most probably would agree that an excess of
      mandibular growth would be helpful, both to the patient and to the orthodontist.
      The literature features a smattering of evidence that this is precisely the sort
      of pattern one sees in many Class II patients, quite independent of treatment
      strategy. There is, however, a tendency to expect (and perhaps to see) favorable
      growth only in functional-appliance patients. As a result, growth modification
      therapy may receive more credit than it deserves in the world of optimistic,
      albeit uncontrolled, clinical observations and impressions. In the present study,
      the pattern of sagittal maxillo-mandibular growth and/or displacement ("apical
      base change") was examined in 120 Class II patients treated with the edgewise
      appliance. Regardless of treatment (extraction or nonextraction), 9 out of 10
      showed a pattern of change in which the mandible advanced relative to the
      maxilla. It is concluded that an assessment of treatment alternatives, especially
      those designed to modify growth, must employ this favorable pattern as the
      baseline from which the effects of growth modification are judged. Methods of
      factoring out the "good growth" that commonly accompanies fixed-appliance therapy
      are discussed within the context of evaluating the effects of functional
      appliances.

PMID- 9573876
TI  - Orthodontic adhesives and bond strength testing.
AB  - A bracket bond failure is a frustrating occurrence in orthodontic practice.
      Because the location of the bond failure may indicate the probable cause, it is
      important to understand the significance of "bond strength" in a clinical
      application. Bonding in orthodontics can be studied using controlled clinical
      models or in vitro using simulated clinical models or more fundamental, isolated
      substrate models, in which bonding of an adhesive to tooth structure or a bracket
      is studied independently. With numerous adhesives and orthodontic band and
      bracket materials available as well as other orthodontic substrates besides
      enamel, such as esthetic ceramic restorations, in vitro models play an important
      role in characterizing the bonding potential of new systems. This article reviews
      bonding of orthodontic brackets and bands using various orthodontic adhesives to
      dental substrates from the perspective of bond strength and its measurement.

PMID- 9573877
TI  - Orthodontic wire: a continuing evolution.
AB  - Wires have substantial structural presence in active and retentive orthodontic
      therapy. Wires, and auxiliaries fabricated from wire, may deliver force to
      produce dental displacements, they may attempt to prevent unwanted displacements,
      or they may simply carry force from one location to another within the
      dentofacial complex. Wires may have relatively simple or rather convoluted
      geometries. The most prominent wire in clinical orthodontic treatment is the
      "arch wire." Marketed in just two, symmetrical, cross-sectional shapes, its sizes
      are numerous, and arch wires are manufactured of a variety of metallic alloys and
      compositions. The primary objective of this article is to trace the history of
      arch wires over the past century, considering the evolution from the stiff arch
      bow to the wire exhibiting Hookean material behavior, from the precious metal to
      the stainless steel to the titanium alloys, and into the era of the
      "superelastic" wire and a thermomechanical behavior decidedly more complex than
      its predecessors. Timely, relevant questions that are addressed herein pertain to
      the current "state-of-the-art" of orthodontic wires, the extent to which the
      mechanics of the "old" and new wires are understood, and the anticipated arch
      wire advancements in the near future as a new millennium approaches.

PMID- 9573879
TI  - Ceramic brackets: something old, something new, a review.
AB  - This article reviews some of the characteristics of ceramic brackets that are of
      particular interest to the clinician. Various factors that may significantly
      influence bond strength and bracket removal are discussed. The information
      provided should enable the clinician to debond ceramic brackets safely applying
      available scientific information.

PMID- 9573878
TI  - Friction between different wire-bracket configurations and materials.
AB  - Friction opposes tooth motion whenever sliding mechanics is employed.
      Understanding what friction is and how to manage it is of paramount importance to
      the successful practitioner. In this article, the coefficients of friction are
      summarized between different arch wire-bracket couples as a function of material,
      geometric, and external parameters. From this vantage point, friction can then be
      evaluated within the context of other factors that affect sliding-binding and
      notching.

PMID- 9573880
TI  - Force degradation in elastomeric chains.
AB  - Elastomeric chains are a frequent choice for delivering forces required to close
      spaces orthodontically. Unfortunately, these forces degrade over time. Open and
      closed chains from six orthodontic suppliers were evaluated over time. For both
      types and for all suppliers, the greatest loss of force occurred within the first
      hour. During the next 2 to 4 days, forces delivered continued to fall but at a
      slower rate. Beyond that time, in general, forces delivered remain nearly
      constant but at a level lower than originally available. The amount of the force
      delivered at 28 days ranged from 85% to 30% of that available at the time of
      placement. At 28 days, gray chains from all suppliers delivered forces greater
      than 100 g.

PMID- 9573881
TI  - Corrosion of orthodontic devices.
AB  - A brief overview of the theory of corrosion and the formation of galvanic couples
      is presented, followed by a discussion of the metals and alloys used in the
      fabrication of orthodontic appliances and devices. Attention is paid to the
      factors that contribute to establishment of corrosion cells in the mouth.
      Although oral corrosion generally does not cause significant destruction of
      metal, it can elicit in patients adverse physiological responses such as local
      irritation and metal hypersensitivity. There are indications that orthodontic
      treatment may lower the incidence of nickel hypersensitivity. Destructive attack
      on orthodontic appliances does occur, however, when certain types of denture
      cleanser are used to clean appliances that contain soldered joints.

PMID- 9573882
TI  - The need for standardization of test protocols.
AB  - This article reviews the current status of standardization in orthodontic
      products. The role of the American National Standards Institute and the American
      Dental Association is described. A review of laboratory testing for the
      evaluation of frictional forces and bond strength in orthodontics is discussed.
      The need for standardization in test protocols is emphasized to obtain valuable
      interpretation and use of data generated by researchers. Standardization of test
      protocols will lead to improved standards for orthodontic products and ultimately
      higher-quality products for orthodontists and their patients.

PMID- 9573883
TI  - Principles of dentofacial orthopedics.
AB  - The differences in the response of patients to the same orthodontic treatment
      are, to a great extent, the result of variability in the direction and rate of
      craniofacial growth. Furthermore, there is currently little scientific evidence
      that the temporary improvement of skeletal relationships from orthopedic
      appliances will alter the craniofacial skeleton on a permanent basis. However,
      contemporary literature is beginning to show that certain appliances may be more
      effective than others at a specific point in the growth process. Timing of
      treatment in a patient is becoming of increased clinical importance. A review of
      the anatomy of palatal expansion indicates that expansion is much greater in the
      anterior portion of the palate, in both horizontal and vertical planes.
      Assessment of skeletal maturity for treatment timing and growth prediction is
      most commonly performed with the hand/wrist radiograph. A new method is presented
      which uses epiphyseal and diaphyseal widths and fusion of selected phalanges to
      determine the relative position of the individual on the pubertal growth curve.
      Skeletal maturity assessment is a traditional attempt to judge physiological
      development. The future of craniofacial growth assessment lies in the development
      of physiological measurements which are both replicable and valid and clinically
      feasible. The data from these studies provides information to allow better
      quantitative diagnosis and treatment as well as objective assessment of the
      treatment outcome.

PMID- 9573884
TI  - Longitudinal evaluation of growth changes in Class II division 1 subjects.
AB  - Longitudinal records from the Ohio State University Growth Study were used to
      compare the skeletal growth changes between Class II division 1 and Class I
      female subjects between ages 7 and 14. Tensor analysis was used to determine the
      yearly growth rate and direction. No significant difference was found in cranial
      base dimension between the Class I and Class II subjects. In Class II subjects,
      the maxilla (S-N-A) was found to be normally related to the cranial base.
      However, mandibular position (S-N-B and S-N-Pog) was found to be significantly
      more retrusive in Class II when compared with Class I subjects. Mandibular length
      (Ar-Gn) and corpus length (Go-Gn) were found to be shorter in Class II subjects.
      The ratio of PFH to AFH was found to be smaller in Class II subjects. This is
      particularly apparent during the pubertal growth period. The y-axis and
      mandibular plane angle were more open in Class II subjects which also contributed
      to the retrusive position of the mandible. Maxillo-mandibular difference (A-N-B)
      between Class I and II subjects was present at age 7 and persisted through
      puberty, maintaining a greater angle of convexity (A-N-Pg) in Class II subjects.
      These results suggest that Class II malocclusion can be detected early. The
      majority of the Class II cases showed mandibular skeletal retrusion or a
      combination of horizontal and vertical abnormalities of the mandible rather than
      maxillary protrusion. These skeletal differences remain through puberty without
      orthodontic intervention. Individual variations were found within each type of
      malocclusion.

PMID- 9573885
TI  - The effects, limitations, and long-term dentofacial adaptations to treatment with
      the Herbst appliance.
AB  - The purpose of this article is to summarize the existing scientific data with
      respect to the short- and long-term effects of the Herbst appliance on the
      occlusion and on the maxillo/mandibular complex. The article also discusses the
      treatment indications and possible treatment limitations. The Herbst method is
      most effective in the treatment of Class II malocclusions. Long-term stability
      seems to be dependent on a stable cuspal interdigitation. Marked mandibular
      morphological changes occur during therapy and sagittal condylar growth is
      increased. Posttreatment, most of the mandibular morphological changes revert and
      no long-term influence of Herbst treatment on mandibular growth can be verified.
      The appliance effect on the maxillary complex can be compared with that of a high
      pull headgear. Without proper retention, however, this effect is of a temporary
      nature. Herbst treatment is especially indicated in the permanent dentition at or
      just after the pubertal peak of growth. Mixed dentition treatment is not
      recommended, as a stable cuspal interdigitation after therapy is difficult to
      achieve and relapses are prone to occur. In the nongrowing patient, the appliance
      should be used with great caution.

PMID- 9573886
TI  - Facial growth of skeletal Class III malocclusion and the effects, limitations,
      and long-term dentofacial adaptations to chincap therapy.
AB  - This article outlines the authors' research findings on the craniofacial growth
      of untreated skeletal Class III malocclusion, as well as the short-term and long
      term effects of chincap orthopedic force for controlling Class III mandibular
      growth. Skeletal Class III malocclusion is believed to be the result of excessive
      growth of the mandible with respect to the maxilla and/or cranial base. The
      results of the authors' longitudinal studies show similar maxillary and
      mandibular incremental growth change during prepubertal, pubertal, and
      postpubertal periods when compared with Class I subjects. Therefore, it seems
      reasonable to assume that the skeletal framework of the Class III malocclusion
      must have been established before the prepubertal growth period. As for treatment
      with chincap appliances, the study on short-term and long-term effects indicate
      that, on average, the skeletal profile is greatly improved during the initial
      stages of chincap therapy. However, such changes are rarely maintained during
      pubertal growth period. Treatment with chincap appliances seldom alters the
      inherited prognathic characteristics of skeletal Class III profiles after
      completion of growth.

PMID- 9573888
TI  - Combined rapid maxillary expansion and protraction facemask in the treatment of
      Class III malocclusions in growing children: a prospective long-term study.
AB  - A prospective study of 28 growing children (mean age of 8 years 3 months) with
      Class III malocclusions was consecutively treated using rapid maxillary expansion
      and maxillary protraction. All patients were treated from a negative overjet to a
      positive overjet and from a Class III dental malocclusion to a Class I dental
      relationship. For each patient, a lateral cephalogram was taken before treatment
      (T1), immediately posttreatment (T2), and after an observation period (T3)
      averaging 2 years 5 months. Using analysis of variance, the cephalograms were
      analyzed to determine skeletal and dental changes resulting from treatment. Long
      term changes (2 years 5 month observation period) were also evaluated. Results
      showed that immediately posttreatment, the maxilla moved anteriorly a mean of
      1.54 mm and Sella-Nasion-A point increased 0.87 degree. The maxillary teeth moved
      anteriorly 2.73 mm and proclined 5.23 degrees, while the mandible rotated in a
      downward and backward direction. Long-term, the anterior position of the maxilla
      was maintained, but some of the Class III correction was lost because of
      mandibular growth. Comparison of this study's results to Riolo's longitudinal
      Class I data showed that, overall, rapid palatal expansion and maxillary
      protraction produced a small orthopedic effect with a moderate dentoalveolar
      effect which together contributed to the correction of the Class III
      malocclusion.

PMID- 9573887
TI  - Treatment response and long-term dentofacial adaptations to maxillary expansion
      and protraction.
AB  - The purpose of this article is to summarize the short-term and long-term results
      of the authors' clinical prospective study on the treatment of Class III
      malocclusion using the protraction facemask. An attempt is made to answer
      questions pertaining to this treatment modality. Twenty patients with skeletal
      Class III malocclusion were treated consecutively with maxillary expansion and a
      protraction facemask. A positive overjet was obtained in all cases after 6 to 9
      months of treatment. These changes were contributed to by a forward movement of
      the maxilla, backward and downward rotation of the mandible, proclination of the
      maxillary incisors, and retroclination of the mandibular incisors. The molar
      relationship was overcorrected to Class I or Class II dental arch relationship.
      The overbite was reduced with a significant increase in lower facial height. The
      treatment was found to be stable 2 years after removal of the appliances. At the
      end of the 4-year observation period, 15 of the 20 patients maintained a positive
      overjet or an end-to-end incisal relationship. Patients who reverted back to a
      negative overjet were found to have excess horizontal mandibular growth that was
      not compensated by proclination of the maxillary incisors. A review of the
      literature showed that maxillary expansion in conjunction with protraction
      produced greater forward movement of the maxilla. Maxillary protraction with a 30
      degrees forward and downward force applied at the canine region produced an
      acceptable clinical response. The reciprocal force from maxillary protraction
      transmitted to the temporomandibular joint did not increase masticatory muscle
      pain or activity. Significant soft tissue profile change can be expected with
      maxillary protraction including straightening of the facial profile and better
      lip competence and posture. However, one should anticipate individual variations
      in treatment response and subsequent growth changes. Treatment with the
      protraction facemask is most effective in Class III patients with a retrusive
      maxilla and a hypodivergent growth pattern. Treatment initiated at the time of
      initial eruption of the upper central incisors helps to maintain the anterior
      occlusion after treatment.

PMID- 9573889
TI  - Distraction osteogenesis: application to dentofacial orthopedics.
AB  - Distraction osteogenesis is a surgical-orthopedic method for lengthening bone by
      separating or distracting a fracture callus. This technique has a long history in
      limb lengthening and has recently been used to lengthen mandibles and maxillae in
      human patients. Distraction osteogenesis represents a powerful method of
      producing unlimited quantities of living bone which can be formed along any plane
      of space. Because this method uses local host tissue, it offers many advantages
      over bone grafting. In the author's experience, large (10-22 mm) antero-posterior
      and vertical corrections of mandibles can be achieved using this technique. The
      purpose of this article is to review its biological basis and discuss recent
      clinical applications. This article reviews the history, theory, current
      management, and limitations of distraction osteogenesis in treating craniofacial
      anomalies.

PMID- 9573890
TI  - Nurses in the media.

PMID- 9573891
TI  - Beyond pillow fluffing.

PMID- 9573892
TI  - Loss of program?

PMID- 9573893
TI  - Trauma re-enacted.

PMID- 9573894
TI  - Plane crash challenged northern Manitoba RNs.

PMID- 9573895
TI  - Whatever happened to the national forum on health?. Interview by Barbara Sibbald.

PMID- 9573896
TI  - Learning the ropes through mentoring.
AB  - In the past, students entering the first year of a nursing program were often met
      by a "big sister." The role of the big sister was to help a new student adjust to
      residence and hospital life through a friendly attitude and informal
      conversation. As nursing education moved from hospital schools of nursing to
      colleges and universities, the strictly regimented life of students living and
      working in close proximity was eliminated, and the role of big sister was lost.

PMID- 9573897
TI  - Gender differences in work and family life.
AB  - Work. What comes to mind? Most of us think in terms of the work for which we are
      paid or the jobs that we would like to have. Seldom do we also think of the
      things we do at home, the care that we provide for our families. Yet, this unpaid
      work can influence our job, just as the demands of the workplace can affect our
      home life. Together, the expectations of both types of work can sometimes be over
      whelming.

PMID- 9573898
TI  - Hospital to home evidence-based education for CHF.
AB  - Congestive heart failure (CHF) is a significant health problem in Canadian adults
      and continues to be a leading cause of morbidity and mortality. It has been cited
      as the most rapidly growing category of cardiovascular disorder. There is little
      likelihood that patients experiencing CHF will leave the health care system until
      death. Typically, they move between health care sectors, being repeatedly
      admitted and discharged from each. In our system today, where institutional and
      community sectors are separately organized, separately funded and poorly linked
      at the point of service delivery, these patients are at high risk for
      discontinuity of care.

PMID- 9573899
TI  - [The adolescent with cleft lip and palate].
AB  - Research studies afford an in-depth look at the problems experienced by
      adolescents born with a cleft lip, a cleft palate or cleft lip and palate. If not
      addressed, their problems can multiply with each successive stage of development.
      An interdisciplinary team, where the adolescents themselves play an important
      role, is one of the best means of helping them come to terms with the
      consequences of the abnormality. The nurse should be a key member of the team. To
      help adolescents cope with their situation now and in the future, the author
      promotes a holistic and humanistic approach. Here, she sees nurses creating
      therapeutic alliances as educators. She recommends that nurses assert themselves
      more as professionals and as essential resources. Her doctoral thesis proposes a
      training model to this effect.

PMID- 9573900
TI  - A timely risk management resource.
AB  - The Hospital Information Services program and the work of the HLC members has
      resulted in a significant increase in the number of physicians and institutions
      willing to co-operate with bloodless treatment of patients. Over a five-year
      period the number of physicians willing to co-operate in this matter has
      increased from 5,000 to more than 50,000 in 65 countries. This dramatic increase
      in the number of informed co-operative clinicians has also resulted in the
      development of more than 80 bloodless surgery and medical centres in various
      countries.

PMID- 9573901
TI  - Lessons learned.

PMID- 9573902
TI  - Supporting clients with undiagnosed symptoms.
AB  - An investigation for serious illness can be terrifying for the client. While
      diagnostic procedures are a high priority, a supportive interpersonal approach
      for the fear the client is experiencing is also a significant aspect of client
      care. The nurse is in the ideal position to provide such support and have a
      significant impact on the client's psychological state.

PMID- 9573903
TI  - Emergency discharge planning team.

PMID- 9573904
TI  - Does Canada need pharmacare?

PMID- 9573906
TI  - Lymphedema following prostatectomy and radiation therapy.

PMID- 9573905
TI  - Implementing change. A complex phenomenon.

PMID- 9573907
TI  - HOPE. Home Care Outreach for Palliative Care Education.
AB  - PURPOSE: The goal of this project was to develop and test an educational program
      to extend the principles of palliative care into home-care agencies. The specific
      aims were: 1) to assess current practices within select home-care agencies
      regarding care of the dying; 2) to design the educational program, the HOPE (Home
      Care Outreach for Palliative Care Education) curriculum, to include relevant
      content for realistic implementation in home-care agencies; 3) to implement the
      HOPE project in two home-care agencies; and 4) to assess outcomes of the project
      and plan for future dissemination to home-care agencies and organizations.
      DESCRIPTION OF PROGRAM: A pilot project developed and tested five training
      modules including overview of end-of-life care, pain management, symptom
      management, communicating with patients and families, and the death event. A
      needs assessment survey completed by 134 home-care agencies provided input for
      the training course development. The five-part curriculum was developed by an
      interdisciplinary team of investigators and consultants and implemented in two
      agencies with 52 staff members participating. Two agencies then were selected to
      participate in pilot testing the curriculum. Precourse and postcourse surveys
      provided evaluation of the program content. RESULTS: Results from the home-care
      agency survey demonstrated the need for improving end-of-life care. Only 32% of
      nonhospice agencies reporting the availability of specially trained nurses for
      care of the terminally ill, and only 16% of the agencies reported providing such
      training. Pilot testing of the HOPE curriculum suggested that it was well
      received by staff members. Assessment of both self-effectiveness and agency
      effectiveness revealed greater comfort with content such as communication and
      other symptom management followed by the areas of pain management, managing the
      death at home, and cultural issues in end-of-life care. The overall rating of end
      of-life care increased from a mean rating of 5.97 to 7.42 for self-assessment and
      from 6.59 to 7.94 for agency assessment (on a scale of 0 to 10, with 0 = not at
      all effective to 10 = very effective). This project identified areas of education
      needed to improve care at the end of life. The HOPE curriculum will be refined
      and extended to reach other home-care agencies to benefit their staffs and the
      patients they serve. CLINICAL IMPLICATIONS: Home care agencies provide extensive
      care to patients and families facing many physical and psychosocial demands at
      the end of life. Palliative care education is important to support home-care
      professionals across all disciplines in optimum end-of-life care. This education
      should focus on aspects of physical care, such as treatment of pain, dyspnea,
      confusion, and fatigue, and also to address decisions about physical care, such
      as hydration/nutrition at the end of life. Psychosocial dimensions of care at
      home can be improved by attention to issues such as communication with dying
      patients and families, cultural considerations, and the special care required at
      the time of the actual death at home.

PMID- 9573908
TI  - Self-Help Intervention Project. Women receiving breast cancer treatment.
AB  - PURPOSE: The purpose of this study was to determine the efficacy of self
      care/self-help promotion and uncertainty management interventions offered by the
      Self-Help Intervention Project (SHIP) for women receiving chemotherapy, radiation
      therapy, or hormone therapy for breast cancer. DESCRIPTION OF STUDY: One hundred
      ninety-three women were randomly assigned either to one of three intervention
      groups (self-help course, uncertainty management, or self-help course plus
      uncertainty management) or to a control group. Data were analyzed by a repeated
      measures multivariate analysis of variance procedure using a two-level blocking
      factor (high and low resourcefulness) and four outcome variables (self-care, self
      help, psychological adjustment, and confidence in cancer knowledge). Data were
      collected at baseline (T1), which was after initiation of adjuvant therapy,
      allowing for the emergence of treatment-related side effects; 6 to 8 weeks after
      T1 (T2); and 3 months after T2 (T3). RESULTS: At baseline, women having high
      resourcefulness compared with women having low resourcefulness evidenced greater
      self-care, self-help, psychological adjustment, and confidence in cancer
      knowledge. Participation in SHIP interventions resulted in higher levels of self
      care, self-help, psychological adjustment, and confidence in cancer knowledge by
      time effect in a significant number of women regardless of their baseline
      resourcefulness. Women participating in SHIP interventions who had low baseline
      resourcefulness demonstrated the greatest change over time in the outcome
      variables. Post hoc results indicated that the effect primarily was the result of
      changes in psychological adjustment, confidence in cancer knowledge, and self
      care. CLINICAL IMPLICATIONS: The findings of this study address both the
      treatment effect for supportive care interventions and the needs that have
      emerged from review of the last 20 years of supportive care research. Some SHIP
      interventions evidenced more strength than others; data indicated that large
      percentages of women with low resourcefulness who received no SHIP interventions
      experienced a decrement in self-care, self-help, confidence in cancer knowledge,
      and psychological adjustment over the time that they received adjuvant therapy.
      Women's level of confidence in their knowledge about cancer being sufficient for
      self-management and self-help activities was not linked to baseline
      resourcefulness level. Thus, inherent resourcefulness was not a factor in need
      for supportive services that could maintain or increase confidence in cancer
      knowledge usefulness for self-management and self-help. Healthcare providers
      should note that although the women with low resourcefulness benefited the most
      from the interventions, women who evidenced high resourcefulness at baseline
      reported the same level of need for confidence in cancer knowledge and for self
      help.

PMID- 9573909
TI  - Lung cancer in African Americans. A call for action.
AB  - PURPOSE: The authors present information about current trends in the incidence,
      risk factors, types, presentation, and treatment for lung cancer common to all
      Americans and highlight factors that are unique to African Americans. Barriers to
      effective care and strategies for implementing culturally competent programs for
      lung cancer are outlined. OVERVIEW: Disparity in the incidence and mortality
      rates of cancer between African Americans and white Americans has been increasing
      at an alarming rate since 1950. For African-American men and women, lung cancer
      accounted for the largest increase in the incidence of cancer between 1988 and
      1992: African-American men experienced an increase of 170%, and African-American
      women had a dramatic increase of 464%. Lung cancer is by far the most common
      cause of cancer death in this population, accounting for 32% of the mortality
      rate in men and 20% in women. Unfortunately, lung cancer in African Americans has
      received little attention, and culturally competent programs are needed urgently
      to promote lung cancer prevention, early detection, and treatment in this
      population. CLINICAL IMPLICATIONS: Healthcare providers' lack of knowledge about
      cultural influences on care is a barrier to providing adequate healthcare to
      individuals of different ethnic groups. Knowledge about cultural differences,
      respect for individual opinions about health and illness, and ability to
      negotiate differences are essential qualities for health professionals who serve
      culturally diverse populations. Because of the morbidity and mortality rates
      associated with lung cancer in the African-American population, prevention, early
      detection, and treatment programs are needed urgently. However, for these
      programs to succeed, the multidisciplinary cancer care team (nurses, physicians,
      social workers, psychologists, health educators, clergy) must provide information
      and care in culturally appropriate ways. Partnerships with family, extended kin
      networks, and religious and community leaders are essential. Finally, to minimize
      morbidity and maximize quality of life during the illness trajectory,
      comprehensive education and supportive care services are needed for those who
      have been diagnosed with lung cancer.

PMID- 9573910
TI  - Uncertainty in prostate cancer. Ethnic and family patterns.
AB  - PURPOSE: Prostate cancer occurs 37% more often in African-American men than in
      white men. Patients and their family care providers (FCPs) may have different
      experiences of cancer and its treatment. This report addresses two questions: 1)
      What is the relationship of uncertainty to family coping, psychological
      adjustment to illness, and spiritual factors? and 2) Are these patterns of
      relationship similar for patients and their family care givers and for whites and
      African-Americans? DESCRIPTION OF STUDY: A sample of white and African-American
      men and their family care givers (N = 403) was drawn from an ongoing study,
      testing the efficacy of an uncertainty management intervention with men with
      stage B prostate cancer. Data were collected at study entry, either 1 week after
      post-surgical catheter removal or at the beginning of primary radiation
      treatment. Measures of uncertainty, adult role behavior, problem solving, social
      support, importance of God in one's life, family coping, psychological adjustment
      to illness, and perceptions of health and illness met standard criteria for
      internal consistency. Analyses of baseline data using Pearson's product moment
      correlations were conducted to examine the relationships of person, disease, and
      contextual factors to uncertainty. RESULTS: For family coping, uncertainty was
      significantly and positively related to two domains in white family care
      providers only. In African-American and white family care providers, the more
      uncertainty experienced, the less positive they felt about treatment. Uncertainty
      for all care givers was related inversely to positive feelings about the patient
      recovering from the illness. For all patients and for white family members,
      uncertainty was related inversely to the quality of the domestic environment. For
      everyone, uncertainty was related inversely to psychological distress. Higher
      levels of uncertainty were related to a poorer social environment for African
      American patients and for white family members. For white patients and their
      family members, higher levels of uncertainty were related to lower scores on
      adult role behavior (shopping, running errands). For white family members, higher
      levels of uncertainty were related to less active problem solving and less
      perceived social support. Finally, higher levels of uncertainty were related to
      the importance of God for white patients and family care providers. CLINICAL
      IMPLICATIONS: The clearest finding of the present study is that there are ethnic
      differences in the relationship of uncertainty to a number of quality-of-life and
      coping variables. This has immediate implications for the assessment of
      psychosocial responses to cancer and cancer treatment. Much of what is in
      curricula is based on clinical and research experience primarily with white
      individuals. The experience of uncertainty related to cancer and its treatment is
      influenced by the cultural perspectives of patients and their families. To assist
      patients and families with the inevitable uncertainties of the cancer experience,
      healthcare providers need to reconsider their ethnocentric assumptions and
      develop more skill in assessing patient and family beliefs, values, cultural
      perspectives, and the influence of these on patient and family uncertainties.

PMID- 9573911
TI  - An examination of nursing attitudes and pain management practices.
AB  - PURPOSE: The purpose of this evaluation is to examine the relationship among
      nurses' pain management attitudes and pain management practices and to begin to
      explore the theoretical underpinnings that may influence this relationship.
      DESCRIPTION OF STUDY: A convenience sample of 29 female registered nurses working
      in hospice or home health settings participated in an educational program 1 day
      per week for 6 weeks. All participants were asked to complete the Cancer Pain
      Knowledge Inventory and Survey of Expectations and Pain Assessment Questionnaire
      5 weeks before, immediately before, immediately after, 6 months after, and 12
      months after the program. Seventeen participants completed all questionnaires at
      the 6-month follow-up; 16 participants completed all questionnaires at the 1-year
      follow-up. Personal beliefs about pain were evaluated in relation to the
      dimensions and treatment of pain. Intentions and expectations to perform specific
      activities were evaluated in relation to in-depth assessments, equianalgesic
      conversions, demonstration of new ideas, and communication. RESULTS: Nurses'
      attitudes, beliefs, intentions, and expectations about pain and pain management
      influenced nurses' patient care and educational activities. Nurses who believed
      that patients should be pain free and nurses who focused on both the dimensions
      and treatment of pain implemented more pain management activities. In general,
      nurses who had high intentions and expectations performed more pain management
      activities. CLINICAL IMPLICATIONS: Although nurses reported change in attitude,
      and high expectancy for change, feelings of increased credibility, and increased
      motivation as advocates for new approaches to practice, nurses sometimes found it
      difficult to implement new practices because of constraints in time and
      collaborative efforts. To implement new knowledge and achieve individualized
      goals for change, nurses must be allowed adequate time to analyze the
      relationships between their beliefs about pain and the ways that they solve
      patients' pain problems. In addition, more support for multidisciplinary
      collaboration is needed.

PMID- 9573912
TI  - Nutritional resources for patients with cancer and health professionals.

PMID- 9573913
TI  - Partnering to create patient education resources on breast cancer.

PMID- 9573914
TI  - Serotonin antagonists. An update.

PMID- 9573915
TI  - 1997 legislative preview.

PMID- 9573916
TI  - Does the current Illinois Nursing Act address delegation?

PMID- 9573918
TI  - Labor legislation report.

PMID- 9573917
TI  - Nursing Act goes to governor's desk. APRN language on hold because of 11th-hour
      ISMS turnabout. Illinois State Medical Society.

PMID- 9573919
TI  - One of my co-workers talked about INA's new "position paper" on latex allergy.
      What are position papers and how do I use them in my workplace?

PMID- 9573920
TI  - INA decries state subcontracting of nursing positions.

PMID- 9573921
TI  - Cook County Hospital RNs take on restructuring.

PMID- 9573922
TI  - Does the Illinois Nursing Act permit nurses to fill requests for drugs?

PMID- 9573923
TI  - CMH RNs file for INA representation. Children's Memorial Hospital. Illinois
      Nurses Association.

PMID- 9573924
TI  - Professional practice issues. Resources.

PMID- 9573926
TI  - District 10 packs political power!

PMID- 9573927
TI  - Now that I am an RN, can I continue to work as an LPN?

PMID- 9573928
TI  - Nursing Act bills introduced.

PMID- 9573929
TI  - Legislative update.

PMID- 9573930
TI  - Labor legislation.

PMID- 9573931
TI  - Does an RN have the right to refuse to be floated to an area that she/he believes
      they are unqualified for?

PMID- 9573932
TI  - Stop latex sensitization.

PMID- 9573933
TI  - Nursing act measures to be amended into one bill.

PMID- 9573934
TI  - Arbitrator upholds RN's refusal to work unsafe assignment.

PMID- 9573935
TI  - What's arbitration?

PMID- 9573936
TI  - Education funding dominates last week of session.

PMID- 9573937
TI  - INA action stops subcontrator's threats to fire RNs. Illinois Nursing
      Association.

PMID- 9573938
TI  - City clinics threatened with privatization.

PMID- 9573939
TI  - Illinois Nursing Act awaiting governor's signature.

PMID- 9573940
TI  - Governor signs nursing Act. APRN negotiations ongoing with ISMS.

PMID- 9573941
TI  - An open letter to INA nurses.

PMID- 9573943
TI  - Legislative update.

PMID- 9573942
TI  - 1997 INA house of delegates. Proposed reports with recommendations.

PMID- 9573944
TI  - Veto session update.

PMID- 9573946
TI  - INA house of delegates 74th Biennial Convention, October 23-25, 1997.

PMID- 9573947
TI  - APRN licensure bill introduced in the Senate and House.

PMID- 9573948
TI  - Heading back to the workhouse?

PMID- 9573949
TI  - One world, one future.

PMID- 9573950
TI  - Treating dementia.

PMID- 9573951
TI  - Rationing memory.

PMID- 9573952
TI  - Continuing the care debate.

PMID- 9573953
TI  - Assessment of family carers.

PMID- 9573954
TI  - Stroke: the hidden problems.

PMID- 9573956
TI  - Continence care.

PMID- 9573955
TI  - Homeward bound.

PMID- 9573958
TI  - Dementia: serious or not?

PMID- 9573957
TI  - Safe in your hands?

PMID- 9573959
TI  - Role in one.

PMID- 9573960
TI  - Traditional birthing.

PMID- 9573961
TI  - Primary nursing--an alternative approach for midwives.
AB  - In task allocation and team nursing systems the least complex task is given to
      the least trained staff member and the most complex task is given to a more
      skilled worker, registered nurses often do no more than checking up on others.
      Primary nursing is a way of thinking and working with patients that challenges
      outdated and traditional nursing hierarchies and supports the way forward for
      professional nurses. Primary nursing allows nurses to provide consistent
      individualised care and encourages the nurse to practice with greater
      professional autonomy. Task allocation, team nursing and even patient allocation
      methods of nursing are not wholly supportive of individualised and humanistic
      care. In contrast, primary nursing presents a structure in which the care planner
      and principle care giver are the same person. With the focus on helping the
      client to make her own decisions and greater professional autonomy for nurses,
      primary nursing is an ideal method of patient care delivery for the specialty of
      post-natal nursing. The way nursing activities are organised reflects the
      attitude towards holistic care of the patient and primary nursing is an
      unconditional patient-centred method of nursing care delivery and the way forward
      for the professionalism and autonomy of nurses.

PMID- 9573962
TI  - 1997 International Congress of the European Association of Lactation Consultants.

PMID- 9573963
TI  - Service standards for maternal and infant care.

PMID- 9573964
TI  - Parental touch of the neonate: encourage or condemn?
AB  - The available literature regarding parental touch and its use on premature
      infants indicates differing views on whether touch should be encouraged or
      condemned. Findings of this literature review indicate that touch can have a
      detrimental physical effect on the infant, however positive long-term benefits
      for parent and child. The absence of direct guidelines for nursing staff working
      in a neonatal intensive care unit make decisions about parental touch difficult.
      The result from this literature review suggests that guidelines for nursing staff
      need to be established, so that optimum care is provided for both infant and
      parent.

PMID- 9573965
TI  - A review of midwifery legislation in Australia--history, current state & future
      directions.
AB  - The legislative regulation of midwifery in Australia, as elsewhere, governs the
      practice of midwives in the profession and controls the entry of new
      practitioners. Legislation exists in all states of Australia, and since 1992
      there have been marked changes in the nature and scope of legislated control.
      This paper explores the origins of midwifery regulation, the recent changes in
      legislation and reviews the current Acts, Ordinances & Rules governing midwifery.
      In doing so, it examines common themes and areas of discrepancy across the
      country. The implications of both are discussed in terms of present
      implementation and future development.

PMID- 9573966
TI  - Care manager certification--everybody's jumping on the bandwagon.

PMID- 9573967
TI  - Case management: an American's observations of community care in Britain.
AB  - The United States faces a rapidly growing aging population, government reforms,
      and policy shifts to give primary responsibility to the states for programs of
      community-based care for the elderly. At the same time, increasing concern is
      being given to the more effective use of home and community-based services, and
      particularly what role case management might play. Given these changes, much may
      be learned from the 1993 reforms to the British system of community care, which
      made case management the cornerstone of the system and gave primary
      responsibility for community care programs to local social service departments.
      This examination of the programs in Britain, conducted largely through site
      visits and personal interviews with social service staff, describes the successes
      and shortcomings of the implementation of the community care reforms with
      recommendations for program development in the United States.

PMID- 9573968
TI  - Categorical funding to seamless systems of care: the challenge for community
      based primary care providers.
AB  - Integrating categorical funding to design "seamless systems of care" for
      individual patients is a challenge faced by many local community-based providers.
      Providers may choose to develop separate site-specific categorical programs for
      patients with human immunodeficiency virus (HIV) [e.g., specialized treatment
      site or a homeless clinic] or integrate these programs with their general primary
      care population. Regardless of program location, providers have developed
      patterns for finding the most appropriate medical home for a patient with
      multiple categorical risks. Medical records reviews and patient interviews
      indicate the importance of case managers in service coordination, although
      clinical issues appear more readily coordinated than situational ones. Provider
      dependence solely on case managers for service coordination, across sites and
      programs may become problematic in the era of managed care without a supportive
      information system that tracks client use and a records system that integrates
      clinical and social service notes. Local providers have encountered difficulties
      in exchanging essential medical information, even within a single agency, under
      state statutes regarding confidentiality of HIV test results.

PMID- 9573969
TI  - Current applications of case management in schools to improve children's
      readiness to learn.
AB  - Recent interest in case management by elementary and secondary schools has arisen
      out of a growing recognition that schools alone are not prepared to address the
      myriad of health, education, and social service needs of a large number of
      students, particularly children living in poverty. Boys and girls entering
      classrooms hungry, sick, homeless, or otherwise distracted are not ready to
      learn. Improving readiness to learn is a major agenda among educators. Case
      management is one approach many schools are beginning to use to collaboratively
      engage parents, community service agencies, the private sector, and communities
      at large in pursuit of the goal. A promising school-based case management model
      has been developed and successfully field tested by the University of Washington.
      The model operationally defines case management, delineates a delivery structure,
      and includes an evaluation design. Results from a five-year study sponsored by
      the U. S. Department of Education are encouraging. Although several challenges
      persist, the future for school case management use is optimistic. Several
      enhanced variations of the Center for the Study and Teaching of At-Risk Students
      (C-STARS) case management model are now being demonstrated across the country.

PMID- 9573970
TI  - Strategies in a managed care system: one agency's experience.
AB  - On July 1, 1995, the Illinois Department on Aging and Council for Jewish Elderly
      began a 3-year venture called the Managed Community Care Demonstration Project
      (MCCDP). This prospective, capitated system is an offshoot of Illinois Community
      Care Program, the existing fee-for-service program of home and community-based
      services for the poor elderly. The authors describe the genesis of the MCCDP and
      its design as well as the strategies CJE has undertaken to succeed in a managed
      care system. The authors then focus on how the changes have affected the care
      manager's role and responsibilities.

PMID- 9573971
TI  - Case management in the human services. Reflections of public policy.
AB  - One way to examine how case management has become a favored tool of public policy
      is to explore how it has evolved in various human service settings. This article
      compares, describes, and analyzes case management in six program categories: (a)
      for persons suffering from chronic mental illness; (b) in child welfare; (c) in
      community-based long-term care; (d) for children and adolescents suffering from
      severe emotional disturbance; (e) for individuals experiencing substance abuse
      problems; and (f) in the public welfare system. Case management in these settings
      is compared along three dimensions: legislative ad programatic origins; models;
      and outcome measures. The analysis reveals the extent to which case management
      has become a cornerstone of public policy--characterized by cost containment
      accomplished through substantial and continuing reduction in public support for
      human service programs.

PMID- 9573972
TI  - Ethical principles in the enhancement of patient care.

PMID- 9573974
TI  - Improving your bedside manner.
AB  - Positive bedside manners are essential when caring for patients. Positive bedside
      manners should be utilized wherever patients and their significant others are
      encountered. Putting your best foot forward is the first step in establishing a
      therapeutic relationship. Attention to one's professional image is important if
      the client is to see the licensed practical/vocational nurse as someone that can
      be trusted. Next is actively communicating interest and concern. It is also
      important to communicate empathy and respect through words and actions. The LP/VN
      must practice attending skills in order for the patient to experience the
      physical and psychological presence of the nurse. Communicating availability and
      following up on requests promote the establishment of trust. It is important for
      the nurse to avoid defensiveness, maintain a professional manner, answer
      questions honestly, demonstrate integrity, maintain a positive attitude and
      practice intentional encouragement. All the characteristics will demonstrate a
      positive bedside manner and will communicate caring and concern to clients and
      their significant others.

PMID- 9573975
TI  - Nutrition and the client with AIDS.
AB  - The nutritional problems that go along with HIV infection and AIDS are
      significant and in fact contribute to death. Nutrition not only affects overall
      health but one's ability to respond to therapies and quality of life.
      Malnutrition and "wasting syndrome" result from compromised nutritional status.
      Early detection and intervention can decrease the dramatic problems caused by
      these conditions. Regardless of the stage of illness, Medical Nutrition Therapy
      needs to be individualized and prioritized as an integral part of one's total
      care.

PMID- 9573976
TI  - Math skills for nurses.

PMID- 9573977
TI  - Mental health: what do we know, how did we find it out and what does it mean for
      nurses?
AB  - In recent years service providers, practitioners and academics have all moved
      away from the term mental illness in favour of mental health. At the same time
      nurses have been increasingly asked to go beyond work aimed at the alleviation or
      reduction of mental illness and to actively promote mental health. Such a
      perspective acknowledges that those who experience mental illness can equally
      experience and have the potential for mental health. In this paper we review key
      works from within psychology and health promotion (including medical sociology)
      that have shed light on the factors that influence mental health in its positive
      sense. Throughout the review we are careful to reflect on the role that research
      methods have played in constructing our current understanding of mental health.
      The aim of the review is to provide nurses with the knowledge that is necessary
      to undertake the challenge of promoting mental health in a practical but also
      reflective way.

PMID- 9573978
TI  - The ideal role of the nurse teacher in the clinical area: a comparison of the
      perspectives of mental health, learning difficulties and general nurses.
AB  - This paper reports findings from a study that explored trained nurses' and
      student nurses' perceptions of the nurse teachers' ideal role in the clinical
      area. Findings demonstrate a dichotomy of opinion regarding the ideal role of the
      nurse teacher in the clinical area that relates to the nursing specialties in
      which trained nurses work. Trained nurses working in general nursing areas
      favoured a product-focused, inspectorate supervisory role for nurse teachers.
      Conversely, trained nurses working in mental health and learning difficulties
      areas favoured a supportive, supervisory role for the nurse teacher that
      emphasized the learning process and encouraged reflection. The consequence of the
      different models used for student nurses' experience of supervision are discussed
      and the issue of nurse teachers' clinical credibility is explored. It is
      suggested that trained nurses, nurse teachers and student nurses should be
      involved in negotiating and constructing the role that nurse teachers play in the
      clinical area.

PMID- 9573979
TI  - Managed mental health care: problems and possibilities.
AB  - Case management has become an established organizational approach to mental
      health care. However, a recent development of case management, known as 'managed
      care' has received only limited attention in the UK and this has been confined to
      acute medical or surgical hospital care. The potential of managed care as applied
      to mental health care is uncertain. This paper clarifies the nature of managed
      care and discusses its relevance to mental health care, in particular to the care
      of people suffering from schizophrenia. The high incidence and heavy resource
      demands of this user group makes these people an ideal focus for managed care.
      However, there are conceptual and practical problems hindering its development
      and implementation, including: the variability and unpredictability of the
      disease process of schizophrenia; challenges of outcome measurement; and problems
      relating to the current organization of mental health care.

PMID- 9573980
TI  - The mental health experiences of gay men: a research study exploring gay men's
      health needs.
AB  - As part of a qualitative study exploring the health needs of gay men, undertaken
      in the Lothian area of Scotland (Robertson & Hutcheson 1995), the mental health
      needs of gay men were elicited through focus groups and individual interviews. A
      grounded theory approach (Glaser & Strauss 1967) was used to analyse the
      responses from a sample of 37 gay men. This research followed a social
      interactionist approach and examined from the respondents' stance the effects of
      being perceived as deviant and the subsequent impact on self-identity and self
      esteem. The findings were that there is a reluctance amongst gay men to disclose
      their sexuality in health care settings which results in mental health needs
      remaining unrecognized by health professionals. The research also showed that the
      respondents faced profound social difficulties when coming to terms with their
      sexuality, a process that can occur throughout their life time. Those who were
      married faced the strain of living two lives and cited alcohol misuse and
      depression amongst the effects of this stressful lifestyle.

PMID- 9573981
TI  - The changing emphasis of mental health and learning disability nurse education in
      the UK and ideal models of its future development.
AB  - This paper reports the findings of a research study funded by the English
      National Board for Nursing, Midwifery and Health Visiting (ENB), which explored
      the impact of community care reforms on mental health and learning disability
      nurses and their practice. In this study we were struck by the divergent views of
      our respondents about the nature of mental health and learning disability nursing
      as practice disciplines and the implications of these views for the future shape
      of preregistration educational preparation. We noted, in particular, the debate
      between those who advocate what is referred to as specialist educational
      preparation and others who favour generic preparation. The specialist-generic
      debate is relevant to nursing as a whole but was magnified in the context of our
      study because genericism was perceived by many of our respondents as a threat to
      the minority branches and especially to those (arguably mental health and
      learning disability) that are not rooted in the biomedical tradition of general
      nursing. This paper seeks to contribute to this debate as it impinges on the two
      nursing specialties by developing models of future nurse education grounded in
      the empirical data from our research and interrogating them to draw out their
      central features. Two models are clearly independent: the 'specialist' and the
      'generic' models. Another three models are partial in that they draw upon the
      first two: the 'pragmatic' model, the 'unity-of-nursing' model, and the 'social
      care' model. A common feature of the pragmatic and unity-of-nursing models is
      that they support the existing DipHE programme, which is now the dominant form of
      preregistration nurse preparation in the UK. The social care model is applicable
      principally to learning disability nursing.

PMID- 9573982
TI  - The use of leisure activities in a therapeutic community.
AB  - This paper is concerned with the use of social and leisure activities as part of
      nursing work in a therapeutic community. It describes this element in the
      therapeutic programme of the Cassel Hospital. There is a brief introduction to
      the general principles of the therapeutic community and then to the nurses' role
      at the Cassel Hospital. The work in the sphere of social and leisure activities
      is seen as consistent with these principles. The structures enabling social and
      leisure activities to be integrated into the work of the hospital are described.
      Therapeutic opportunities are outlined, which arise when nurses work alongside
      patients in the course of such activities. This also serves to illustrate
      therapeutic community practice. There follows a discussion of the clinical
      significance of the voluntary element in this area of practice and of the related
      problems. Jacques' conceptualization of work and resistance to work are used at a
      number of points to link issues raised in the paper to existing psychodynamic
      theory.

PMID- 9573983
TI  - Community mental health nurses' perceptions of their practice as a factor in the
      reform of community-based mental health services in Nova Scotia.

PMID- 9573984
TI  - Views on community care for people with mental health problems: a discourse
      analysis of argument and accountability in a Scottish community.

PMID- 9573986
TI  - Kansas EMS/trauma plan update.

PMID- 9573985
TI  - Advance decision making for psychiatric care.

PMID- 9573987
TI  - Central America health care delivery.

PMID- 9573988
TI  - CHIP: Child Health Insurance Plan Part II.

PMID- 9573989
TI  - National Council of State Boards of Nursing adopt interstate compact language.

PMID- 9573990
TI  - Task force to study the prescribing of controlled substances by advanced
      registered nurse practitioners.

PMID- 9573991
TI  - Nursing in Bolivia brings rewards, challenges.

PMID- 9573992
TI  - Prevention of human rights abuse takes RN to South Africa.

PMID- 9573993
TI  - Health care in a low-tech society: nursing in rural Zimbabwe.

PMID- 9573995
TI  - Finding the right fit. Podium, poster, paper or publication? (part 1)

PMID- 9573996
TI  - Nurse practitioner SIG takes informal poll.

PMID- 9573997
TI  - Treatment directives and DNR orders saying NO to treatment.

PMID- 9573999
TI  - Volunteerism.

PMID- 9573998
TI  - Legislative update. Patient Safety Act reintroduced in 105th Congress.

PMID- 9574000
TI  - How do you know if your paycheck is correct?

PMID- 9574002
TI  - Rulemaking by the State Board of Nursing.

PMID- 9574003
TI  - Nurses have rights, too.

PMID- 9574005
TI  - Moving into cyberspace.

PMID- 9574004
TI  - A correlational study of variables affecting adolescent pregnancy.

PMID- 9574006
TI  - Code for nurses revisited.

PMID- 9574007
TI  - Nurses have the courage to care.

PMID- 9574008
TI  - Legislative and regulatory agenda. 89th general assembly. 1997.

PMID- 9574009
TI  - A response to "Supervising RNs and advance nurse practitioners: new regulations
      for Missouri".

PMID- 9574010
TI  - A comparison of findings from two checklists for the early detection of skin
      cancer.

PMID- 9574012
TI  - Defending yourself on many fronts. Malpractice isn't all you should worry about
      after a patient care-incident. Here's what you need to know.

PMID- 9574011
TI  - Warning: being gutsy can be habit-forming.

PMID- 9574013
TI  - Legislative update. Governor signs HB 762.

PMID- 9574014
TI  - Midwest baccalaureate nursing education curricular changes in response to health
      care reform.

PMID- 9574015
TI  - Who's afraid of PREP?

PMID- 9574016
TI  - Collaboration and partnership--the trials and successes.

PMID- 9574017
TI  - Thinking about teaching. More learning activities.

PMID- 9574018
TI  - Rights: freedom, free will and the individual.

PMID- 9574019
TI  - Don't hit the writing wall, climb right on over it.

PMID- 9574020
TI  - Are you cut out for a career in research.

PMID- 9574022
TI  - Need to enhance the heritage of Florence Nightingale.

PMID- 9574021
TI  - A hazardous practice.

PMID- 9574023
TI  - Grievance handling do nurses need this skill?

PMID- 9574024
TI  - Hospitalised patients' need for information. A study.

PMID- 9574027
TI  - Asthma, an independent study.

PMID- 9574025
TI  - Quality of Therapeutic Activity Status of coronary heart disease patients at
      ICCU.

PMID- 9574031
TI  - Importance of nursing data.

PMID- 9574030
TI  - Differences among advanced practice nurses, physician assistants, and registered
      nurses.

PMID- 9574032
TI  - Growth demands accountability.

PMID- 9574033
TI  - Invasive Streptococcus pneumoniae: a newly reportable disease.

PMID- 9574034
TI  - Nursing's influence on tobacco intervention.

PMID- 9574036
TI  - Registered nurses and pregnancy: new legal protections in the workplace.

PMID- 9574037
TI  - Patient abuse accusations and the RN.

PMID- 9574038
TI  - Home care: a unique role for mental health nursing.

PMID- 9574039
TI  - Professionals helping professionals.

PMID- 9574040
TI  - Issue: what are some issues that the ONA Council on Practice discussed during its
      1997 meetings?

PMID- 9574041
TI  - Nursing and HIV: changing issues in Ohio.

PMID- 9574042
TI  - [We hoped in vain].

PMID- 9574043
TI  - [Our society needs good Samaritans].

PMID- 9574044
TI  - [Greetings on the 50th anniversary of Pflegezeitschrift. "Working conditions
      ought to improve"].

PMID- 9574045
TI  - [50 years Pflegezeitschrift. When the nurses fell out of the sky].

PMID- 9574046
TI  - [Less fear of contact with alternative measures].

PMID- 9574047
TI  - [One year of hospice hotline in Germany. 10,867 callers needed advice and
      assistance on the topic of dying].

PMID- 9574048
TI  - [The federal board of nursing teachers is being reformed. We are wishing for more
      efficiency].

PMID- 9574049
TI  - [Hospice units. Patients with cancer are being supported to the end. Interview by
      Sibylle Mevenkamp].

PMID- 9574050
TI  - [Local anesthetics and their use: how and where are the various substances
      effective].

PMID- 9574051
TI  - [Assistance in eating and drinking for patients and residents: feeding patients
      may be delegated only after training].

PMID- 9574052
TI  - [Anthroposophic pediatric care. Respecting the patient in his entirety].

PMID- 9574054
TI  - [Lack of communication in medicine: "give and take" might be a way out of the
      crisis].

PMID- 9574053
TI  - [Importance of a nursing model during changes in the hospital: a sweeping
      developmental process has begun within the nursing services].

PMID- 9574055
TI  - [Nursing education and health care system in Nepal. 2. Nurses in Nepal have
      autonomy].

PMID- 9574057
TI  - [The German Alzheimer Society informs. 4: Living in the past].

PMID- 9574056
TI  - [Legal requirements of nursing professionals by nursing insurance: Guidance and
      counseling require extensive professional knowledge from nurses].

PMID- 9574058
TI  - "Gathering our wisdom: American Indian Nursing Summit III".

PMID- 9574059
TI  - Surfing nurses (or fun on the Internet).

PMID- 9574061
TI  - ANA services to "staff nurses". American Nurses Association Board of Directors.

PMID- 9574060
TI  - Check up on your hospital before you check in.

PMID- 9574062
TI  - [Learning to live with seropositivity].

PMID- 9574063
TI  - [Seropositivity. Detection at the Anonymous and Free Screening Center].

PMID- 9574064
TI  - [Seropositivity. Disclosure of seropositivity. A singular discussion with the
      practicing physician].

PMID- 9574065
TI  - [Seropositivity. The seropositive patient in the day hospital. Admission].

PMID- 9574066
TI  - [Seropositivity. Antiretrovirus treatments].

PMID- 9574067
TI  - [Seropositivity. Legislation].

PMID- 9574068
TI  - [Seropositivity. Psychological aspects of HIV infection].

PMID- 9574069
TI  - [Nutrition and seropositivity].

PMID- 9574070
TI  - [Seropositivity. Prospects for the future].

PMID- 9574071
TI  - [Quality: shadows and lights. When quality concerns health].

PMID- 9574072
TI  - [Nurses and grief. Elements for reflection].

PMID- 9574073
TI  - [Professional confidentiality and daily nursing practice].

PMID- 9574074
TI  - [The drug. Composition, Galenic forms and ways of administration].

PMID- 9574076
TI  - [1988, 1998 and tomorrow...].

PMID- 9574077
TI  - [Prenatal diagnosis and surgery].

PMID- 9574078
TI  - [Skin angiomas in children].

PMID- 9574079
TI  - [Angioma. Inherent risks of treatment. Recommendations about the use of lasers].

PMID- 9574080
TI  - [Angioma. Treatment by pulsed dye laser. The nurse's role].

PMID- 9574081
TI  - [The story of Emily. Nursing care plans].

PMID- 9574082
TI  - [The story of Marina. Nursing care plans].

PMID- 9574083
TI  - [Monitoring a newborn at home. Stress and anxiety experienced by the parents].

PMID- 9574084
TI  - [Child therapists--in the plural].

PMID- 9574085
TI  - [The status of children through the ages].

PMID- 9574086
TI  - [Pain in pediatric emergency units].

PMID- 9574089
TI  - Entry-level policy proposed.

PMID- 9574090
TI  - Columbia's problems expose land mines in for-profit health care.

PMID- 9574091
TI  - Green leads local schools, shares experience.

PMID- 9574093
TI  - TNA member prepares tomorrow's nurses.

PMID- 9574094
TI  - [Introductory addresses, honoring the deceased. Opening addresses, honors,
      prizes, membership meeting].

PMID- 9574095
TI  - [Opening address by the president].

PMID- 9574092
TI  - Health improvements.

PMID- 9574096
TI  - [Why doesn't Aphrodite have a nose?].

PMID- 9574097
TI  - [Guidelines from the viewpoint of AWMF (Association of Scientific and Medical
      Societies)].

PMID- 9574098
TI  - [Guidelines in surgery: from the viewpoint of clinical research].
AB  - The concept of clinical practice guidelines is full of sociological conditions
      which cannot be transferred from one country to another without local tailoring.
      The quality of health care emphasizes both individuals and groups, defines the
      probability of desired health outcomes, and requires concordance with
      contemporary professional knowledge. In this context, the experience-based,
      intuitive judgement of experts is heavily underestimated in the Angloamerican
      literature. Clinical guidelines are systematically developed statements which
      assist doctors and patients in finding appropriate health care. They are not
      dictatory in nature. In Germany, a three-phase model is preferred: check lists
      immediately, consensus-processes for intermediate time periods, and finally
      consensus with best-evidence synthesis.

PMID- 9574099
TI  - [Guidelines in surgery: from the viewpoint of the advisory council].
AB  - The Advisory Council for Concerted Action in Health Care recommended 1994 to the
      Association of Scientific and Medical Societies in 1994 that guidelines should be
      established for diagnostics and treatment. The advisory council expects that the
      implementation of such guidelines should improve the quality of medical care.
      Deficits in medical care must be reduced, and unnecessary procedures eliminated.
      Absolute necessities must receive preferential financing from the social health
      insurance as compared with optional procedures. Guidelines are an intelligent
      alternative to undifferentiated cost reduction.

PMID- 9574100
TI  - [Guidelines in surgery: from the viewpoint of health care economics].
AB  - Guidelines support the economic evaluation of surgical procedures. Therefore,
      guidelines should contain cost-benefit information as a basic element. Guidelines
      prompt activities in the health-care system by means of information. Some of the
      information should thus be available and understandable for nonmedical staff,
      too. Guidelines should improve the transparency of surgical outcome to enable
      patients and insured parties to make a more rational choice and thus provide
      their own input into the health care system.

PMID- 9574101
TI  - [Guidelines in surgery: from the viewpoint of the legal process].

PMID- 9574102
TI  - [Guidelines in surgery: from the viewpoint of the surgical expert].

PMID- 9574103
TI  - [Guidelines in surgery: from the viewpoint of quality assurance].
AB  - The German Society for Surgery takes the AWMF's instructions to create effective
      guidelines very seriously. International criteria for guidelines are fully
      accepted, for example, the guidelines for thrombosis prophylaxis. The guide plays
      a very important part in overall quality management, but it cannot replace
      further precautions like risk management, second opinions, or external quality
      control. Despite forensic problems, patients are definitely entitled to
      diagnostic and therapeutic guidelines.

PMID- 9574104
TI  - [Abdominal wall hernias (inguinal hernia, incisional hernia)].
AB  - Within the range of treatment of inguinal hernias, the paper concentrates on the
      following procedures: Shouldice, the "tension-free" repairs of Lichtenstein,
      Rutkow, TIPP, and the laparoscopic procedures TAPP and TEP. An individual,
      selective approach tailored to the type of hernia, as well as the age and
      profession of the patient is recommended. A multicenter study comparing these
      procedures would be useful. Conventional repair of incisional hernias (simple
      closure, Mayo) has a depressing recurrence rate of 30%-40%. Better results are
      obtained by using a synthetic prosthesis, which can be implanted using the sublay
      inlay, or onlay technique.

PMID- 9574105
TI  - [Interdisciplinary guidelines: cholelithiasis].
AB  - Quality management in internal medicine and surgery is especially difficult
      because of the magnitude of these two subjects. Between the years 1994 and 1996,
      the German scientific societies of internal medicine developed the manual
      "Rationelle Diagnostik und Therapie in der Inneren Medizin". The cooperation of
      colleagues was most helpful when the interests of several internal branches were
      involved. An even greater challenge is the development of interdisciplinary
      internal and surgical guidelines, which are presented here for cholelithiasis.

PMID- 9574106
TI  - [Interdisciplinary guidelines: cholecysto- and choledocholithiasis].

PMID- 9574107
TI  - [Interdisciplinary guidelines: inflammatory bowel diseases--Crohn disease,
      ulcerative colitis].
AB  - Guidelines for medical, nutritional, and surgical treatment of Crohn's disease
      have been drawn up recently by gastroenterologists and abdominal surgeons from
      the "Deutsche Gesellschaft fur Verdauungs- und Stoffwechselkrankheiten". These
      data have not yet been published, but are presented here. Medical treatment of
      ulcerative colitis during acute attacks and remission depends widely on the
      extent and activity of the disease. Recently published guidelines for
      surveillance of patients with long-lasting ulcerative colitis to prevent
      colorectal cancer by American gastroenterologists and surgeons are discussed.

PMID- 9574108
TI  - [Interdisciplinary guidelines: inflammatory bowel diseases (Crohn disease,
      ulcerative colitis)].
AB  - Crohn's disease and ulcerative colitis are characterized by common problems and
      findings but also disease-specific differences. The most frequent indication for
      surgery concerns the refractory situation occurring both after and during
      systematic conservative treatment. The aim of surgery in patients with Crohn's
      disease is to induce remission of symptoms by removing the segment of diseased
      bowel. Because of the relatively high rate of postoperative recurrence, extensive
      resections should be avoided. Proctocolectomy with ileal pouch--anal anastomosis
      has become the surgical treatment of choice for most patients with uncontrolled
      ulcerative colitis. This technique offers these patients cure of the disease and
      in most cases a better quality of life.

PMID- 9574109
TI  - [Guidelines in trauma surgery--direction or hindrance?].
AB  - The German Society of Trauma Surgery decided in November 1995 to pass a
      resolution on trauma diagnosis and therapy guidelines. The first eight
      guidelines, dealing with the Diagnosis Related groups relevant for trauma
      patients, have now been completed by the scientific committee of the society and
      is published as a pocket book in July 1997. The content is clearly classified,
      and each guideline is described shortly. This book does not serve as a substitute
      for textbooks and surgical manuals. Guidelines have to be open to new innovative
      trends and should not compel certain diagnostic or therapeutic procedures to be
      used. Instructions may help to reduce costs and to establish necessary
      procedures. Legally these guidelines describe the medical standard and,
      therefore, can not be ignored. They do not replace the medical expert. Guidelines
      require a high degree of expert knowledge. Therefore, they should only be
      published and modified by a scientific society. As guidelines may endanger the
      medical freedom of treatment and development of innovative trends, they need to
      be carefully defined for a wide range of application.

PMID- 9574110
TI  - [Polytrauma and the hospital structure].
AB  - Hospital standards for the care of multiple traumatized patients include certain
      clinical capabilities, special logistics (appraisal of structure), and--even more
      important--algorithms for simultaneous activities in diagnosis and therapy
      (assessment of process). The main goal in the trauma system should be definitive,
      specialized care for the injured in the shortest possible time. Economically
      there is no way of creating a tight network of highly developed trauma centers
      close to every patient. Also primary air-transport by helicopters over some
      distances in every case is not realistic (darkness, weather conditions).
      Therefore, an algorithm that is dependent on regional conditions is needed for
      primary care and stabilization of multiple trauma patients in smaller hospitals
      followed by early transfer to trauma centers. The effectivity of this stepwise
      approach must be compared with primary care in a trauma center. Trauma registers
      are necessary to plan for the future. Quality improvement programs (education,
      system evaluation) should be installed, especially for smaller hospitals bound
      into the trauma system. Financial support is essential for hospitals designated
      for care of multiple traumatized patients in rural areas.

PMID- 9574111
TI  - [Guidelines in trauma surgery--geriatric traumatology].
AB  - The treatment of injuries in elderly patients requires thorough planning.
      Preexisting diseases and the current status determine the priorities and methods
      of treatment. The advantages of extensive preoperative assessment must be judged
      against the risks of a delay in undertaking operative measures. Fracture
      treatment aims at fast, careful and simple fixation, which is nevertheless stable
      and sufficient. Modern methods and implants allow acceptable results to be
      achieved, even under the limitations of modern health care systems.

PMID- 9574112
TI  - [Guidelines in surgery--pediatric traumatology].
AB  - Guidelines for the treatment of fractures in children include social and
      therapeutic parameters, such as adequate hospitalization for children, a
      definitive therapy with a low degree of invasiveness, and a high degree of
      freedom of mobility. The selection of a method is linked to the patient's
      requests. Minimally invasive techniques should be applied in preference.
      Therapeutic strategies should be compared not only with regard to results, but
      also with regard to effectivity and efficiency. There are no strict guidelines in
      therapeutic procedures whatsoever.

PMID- 9574113
TI  - [Guidelines: treatment of distal radius fracture].
AB  - The treatment aim is restoration of adequate length of the radius, adjustment of
      the distal radioulnar joint, alignment of the distal radius joint surface, and
      prevention of reflex dystrophy syndrome. Stable fractures are treated by close
      reduction and a cast for 3-4 weeks, depending on bone stock quality. Instable
      extra-articular fractures are treated by K-wiring using various methods. In case
      of a comminuted dorsal or palmar area, K-wiring is unstable, so additional
      fixation is necessary (autogeneous bone graft + external fixator + plate or
      cast). The external fixator alone or in combination with K-wires is the
      appropriate fixation method all intra- or extra-articular comminuted fractures.
      Palmar or dorsal plate osteosynthesis is highly recommended in palmar or dorsal
      rim fractures (B 3, B 2 type), whereas in C 2 to C 3 fractures additional
      autogeneous graft and/or K-wires or screws are necessary should be used in
      combination with autogeneous graft, according to the fracture pattern. Ligament
      injuries or luxation in the carpal row must be looked for precisely and treated
      according to the injury pattern.

PMID- 9574114
TI  - [Guidelines in oncologic surgery--malignant thyroid tumors].
AB  - Guidelines for a highly effective radical treatment protocol of thyroid cancer
      are based on its histopathological classification. The bases are total
      thyroidectomy, including the central lymph node compartment parathyroidal and
      paratracheal, extended to uni- or bilateral cervical lymph node dissection in
      case of clinical manifestation or very advanced tumor stage. Postoperative
      control or treatment by radioiodine is obligatory for all differentiated thyroid
      carcinoma. Reoperative surgery is useful for locoregional recurrence. Limited
      unilateral thyroid surgery is only justified in selected cases of primary tumors
      less than 1 cm diameter in a low-risk patient group.

PMID- 9574116
TI  - [Guidelines for stomach carcinoma and lymphoma].
AB  - The manual is based on a consensus-conference of the oncological study groups
      surgery, internal medicine and radio therapy. Additionally to gastrectomy and
      exceptionally the high resection it contains lymphdysection of the second
      compartment. When R0 resection seems impossible preoperatively, a neoadjuvant
      therapy under study protocol should take place. Especially in gastric lymphoma
      the therapeutical variety is large. Therefore taking part in clinical studies is
      urgently required.

PMID- 9574115
TI  - [Guidelines in therapy of esophageal carcinoma].
AB  - Tumor stage and tumor localization (suprabifurcal and infrabifurcal) are the two
      decisive criteria referred to in the surgical treatment of esophageal cancer.
      Complete tumor resection (R0 resection) is a prerequisite for curative efforts.
      The thoracic squamous cell tumors are adequately treated by an abdominothoracic
      resection with abdominal and mediastinal lymph node dissection. The
      transmediastinal approach does not meet the requirements of an oncological
      resection and is only indicated under special conditions. In contrast the distal
      adenocarcinomas (Barrett carcinoma) can be curatively resected by both surgical
      approaches, the transthoracic and the transmediastinal. Presently, an adjuvant
      therapy after R0 resection of esophageal cancer is not indicated outside of
      clinical studies. Neoadjuvant methods in case of a local advanced tumor are
      currently being clinically tested.

PMID- 9574118
TI  - [Oncologic surgery of colon carcinoma].
AB  - Surgical oncology of carcinomas of the colon is also surgery of lymph drainage
      compartments, including radicular ligation of the vessels and tissue planes.
      According to tumor localisation and safety margins at the resection lines,
      standardized surgical procedures with the aim of R0 resection can be defined. R
      classification is a strong independent prognostic factor regarding survival
      benefit. Adjuvant chemotherapy in curative resected colonic cancer UICC stage III
      should be recommended in general but modifications of this regimen must be
      investigated in further studies.

PMID- 9574117
TI  - [Guidelines in therapy of pancreatic carcinoma].
AB  - The definition of guidelines as merely describing a "corridor of action" and the
      existence of numerous up-to-date textbooks on the subject raises the question as
      to their purpose and necessity. This paper provides a critical commentary on
      existing guidelines. Above all it points out that the sections on preoperative
      diagnosis and palliative surgery require amendments barely 8 months after
      publication of the guidelines. Thus while the compilation of guidelines is
      laudable, it is both expensive and time-consuming, and this problem is
      potentiated by the need for constant amendment.

PMID- 9574119
TI  - [Guidelines for surgical and multimodal therapy of malignant soft tissue tumors].
AB  - An optimal treatment of soft tissue sarcomas is influenced by multiple factors.
      The high local recurrence rate is often based on inadequate surgical primary
      therapy. An improvement of prognosis which is still unfavourable in some patients
      can be achieved only if guidelines described in this paper gain increasing
      influence in practice. A treatment concept for soft tissue sarcomas must be
      worked out interdisciplinary within the knowledge of all relevant data. Surgery
      is just one but an essential component of therapy to be placed at the right time.
      To achieve a R0-resection is an important requirement for survival free of
      recurrence. However, the influence of a local recurrence on overall survival
      remains controversial. Amputations should be taken into consideration only after
      exhaustion of all reconstructive procedures available.

PMID- 9574120
TI  - [Guidelines and quality assurance in national and international practice in the
      area of plastic surgery].
AB  - Multiple quality assurance activities in the German plastic surgery association
      are outlined, such as the collection of structural data, inspections of units by
      expert commissions, tracer diagnosis, continuous evaluation of health outcome by
      patient questionnaire, training programs for residents and a credit point system
      for congress activities. Interdisciplinary groups are formed for internal quality
      management within hospitals. EBOPRAS is responsible for accreditation of training
      centers and the European (Union) Board certification. EQUAM activities aim for
      quality improvement of biomaterials. Quality management activities within the
      International Confederation of Plastic, Reconstructive and Aesthetic Surgery
      concentrate on the definition of minimal requirements for training units and the
      establishment of a quality management philosophy.

PMID- 9574121
TI  - [Guidelines and quality assurance in plastic breast surgery].
AB  - Guidelines in Plastic Breast Surgery refer to breast-reduction, breast
      augmentation, correction of an asymmetry and reconstruction of an amputated
      breast. Because of the broad variety of the initial findings and treatment
      strategies and the patients specific interests only short and therefore rough
      guidelines can be given, and these are of little use for surgeons and economists.

PMID- 9574122
TI  - [Guidelines in surgical intensive care medicine].
AB  - In a cooperative effort involving each medical society the joint study group of
      the medical research societies in Germany (AWMF) has established guidelines for
      the diagnosis and treatment of various diseases. Special guidelines which pertain
      specifically to operative intensive care medicine do not exist. However, official
      recommendations have been made for intensive care management in general. These
      have been released with the support of the German Interdisciplinary Society for
      Intensive Care and Emergency Medicine (DIVI). Today, 10 such guide lines exist.
      Also yet the value of those guidelines cannot be assessed. It is beyond doubt
      that besides being of benefit, they do present some dangers. One must point out
      that these guide lines are recommendations and not rules upon which medical
      liability may be based.

PMID- 9574123
TI  - [Guidelines in surgical intensive care medicine--central venous catheter].
AB  - Central venous catheterisation (CVC) is an invasive procedure, which needs a
      severe indication. It allows the measurement of central venous pressure, the
      infusion of hypertonic or irritant solutions, the application of vasoactive drugs
      and an access for special purposes (like pulmonary artery catheter or continuous
      haemodiafiltration). There exist some specific compliations associated with
      insertion and also associated with the CVC being in place. Therefore it is
      necessary to document the indication, the control of placement, the duration of
      catheterisation and the complications.

PMID- 9574124
TI  - [Acute renal failure].
AB  - Acute renal failure is defined as a multifactorial syndrome that occurs-
      depending of definition and selection of patients--in 2%-25% of all ICU patients.
      Most frequent in surgery (approximately 70%), ARF is caused by septic
      complications. Renal replacement therapy is managed today by dialysis,
      hemofiltration or the combination of both. Lethality of ARF ranges from 50% to
      80%. High lethality rates are not related to ARF itself, but to uncontrolled
      septic MOF. The consequences for surgical ICU patients are: First of all,
      protective measures are mandatory. If ARF occurs, septic complications have to be
      considered. Renal replacement therapy has to be integrated into the management of
      septic MOF.

PMID- 9574125
TI  - [Acute lung failure].
AB  - Ever-increasing knowledge of the pathomechanisms and the phasic pathogenesis of
      ARDS has increased the demand for adequate monitoring and has modified
      therapeutic strategies. The influence of monitoring by double indicator dilution
      technique (COLD system) with the close measurement of extravascular lung water on
      the diagnosis and therapy of ARDS is presented. Pressure-controlled ventilation
      (< 35 cm H2O) in combination with moderate PEEP, kinetic therapy (prone position)
      and elective CVVH already in the early stages of ARDS can be regarded as the
      standard therapy. The effectiveness of NO inhalation, prostaglandins and radical
      scavengers still has to be improved in controlled clinical trials.

PMID- 9574126
TI  - [Treatment of increased intracranial pressure in craniocerebral trauma].
AB  - The management of trauma patients with increased intracranial pressure is based
      on maintaining a normal "milieu interne", i.e. avoiding posttraumatic hypoxia and
      hypotension and applying specific treatment modalities, if indicated. If there
      are clinical signs of increased intracranial pressure or signs of cerebral edema
      in the CT scan, monitoring of intracranial pressure is indicated. ICP above 20
      mmHg should be treated and the cerebral perfusion pressure should be maintained
      between 60 and 70 mmHg. Accepted treatment modalities of increased ICP are: 1)
      analgosedation, 2) head elevation, 3) hyperventilation, 4) osmotherapy, 5)
      barbiturate therapy, and 6) THAM (tris puffer).

PMID- 9574127
TI  - [Guidelines in pediatric surgery].
AB  - Guidelines are intended to give more structure and transparency to medical
      procedures and to reduce unnecessary medical costs. The aims of guidelines and
      the claims made upon them are defined and their usefulness is discussed, with a
      short review of special problems in pediatric surgery.

PMID- 9574128
TI  - [Guidelines in pediatric traumatology].
AB  - Guidelines for the treatment of fractures in children must meet the specific
      requirements of the growing organism. Diagnosis must be based on X-ray findings,
      but occasionally also on sonography or MRT. Treatment is successful only after
      one-stage exact reduction and safe, conservative or operative fixation. Secondary
      manipulations or a change in treatment have a negative effect. A growth-induced
      correction of a remaining false position cannot be anticipated. The older the
      child, the more must treatment result in perfect anatomic conditions. Especially
      injuries to the epiphysis require excellent reduction and perfect fixation.
      Damage of the growth plate and/or a posttraumatic false growth demand long-term
      follow-up and subsequent corrective surgery.

PMID- 9574129
TI  - [Pediatric urologic guidelines].
AB  - Because of the enormous progress of science and technology and increasing
      possibilities in diagnostics and therapeutics guidelines are also necessary in
      pediatric urology. Guidelines must have the non-committal character of
      recommendations in order not to reduce the freedom of medical action in diagnosis
      and therapy to the detriment of patient interests. The special premises and
      conditions of guidelines must be defined. Due to the large variety of diseases
      and disturbances in pediatric urology, it is important to limit the number of
      guidelines.

PMID- 9574130
TI  - [Guidelines in surgery of the liver and bile ducts].
AB  - The surgery of biliary ducts and malignant liver tumors is formulated
      illustratively in guidelines in order to assist the physician as well as the
      uninformed patient in their orientation concerning diagnostic, therapeutic and
      prognostic questions. Special attention is paid to diagnostics, which is based on
      both rational and empirical verified arguments. Moreover, the examples presented
      in this study show that guidelines can only be formulated if extensive verified
      knowledge exists; for rare diseases and those about which little is yet known
      guidelines cannot (yet) be formulated.

PMID- 9574132
TI  - [Guidelines in vascular surgery--aneurysm of the abdominal aorta].
AB  - The standard treatment of abdominal aortic aneurysm, including diagnosis,
      indication and method of operation, is being extended by the new method of stent
      graft implantation. Currently it is too early to comment on the optimal technique
      and material. There is too much variation among different stent-graft
      combinations and long-term outcome is unknown, especially concerning the
      longevity of the prosthesis.

PMID- 9574131
TI  - [Acute peripheral arterial occlusion].
AB  - Acute embolic occlusion of a normal artery is best treated by simple "Fogarty"
      maneuver. This procedure is mostly successfully performed even by less
      experienced surgeons. However, if atherosclerotic disease is the underlying cause
      for acute occlusion of the vessel, an experienced vascular surgeon and the use of
      interventional techniques is demanded. In this case, deficits in both experience
      and technical equipment in the operating room frequently lead to avoidable limb
      loss.

PMID- 9574133
TI  - [Guidelines in vascular surgery: acute mesenteric artery occlusion].
AB  - Because of the short ischaemic tolerance time of the intestine in case of acute
      intestinal ischaemia, diagnostic and therapeutic decisions have to be made under
      extreme time pressure. Because there are still no reliable and quickly available
      diagnostic criteria for excluding or confirming acute intestinal ischaemia,
      careful exploration of anamnestic history and the angiography remain the
      cornerstones of early diagnosis. Depending on the intraoperative findings and the
      stage of the disease, therapy consists of resection of the diseased bowel,
      revascularisation of the occluded vessel or the combination of both methods.
      Additional conservative therapeutic measures are still in an experimental stage.

PMID- 9574134
TI  - [Guidelines in vascular surgery--occlusion of the femoral artery].
AB  - Indications for reconstructive procedures in femoral artery occlusions depend
      only on the clinical symptoms which the patient presents. Because of the good
      prognosis in this arterial region the patient should be treated as conservatively
      as possible. An invasive therapy is rarely needed. The progressive basic
      character of the disease should be kept in mind, making routine monitoring at
      least twice a year mandatory. Only a well-skilled vascular surgeon in a well
      equipped hospital is allowed to perform reconstructive vascular surgical
      procedures in this region.

PMID- 9574135
TI  - [Guidelines for quality assurance in bronchial carcinoma].
AB  - Quality management in lung cancer needs interdisciplinary cooperation among
      thoracic surgeons, pneumologists, oncologists and radiologists. This requires
      defined standards in the structure, process and outcome quality of the involved
      departments. The German Society for Thoracic Surgery has established a concept
      for internal and external quality assurance of operative treatment of lung
      cancer, according to the requirements for quality management developed by
      Selbmann. The future calls for the integration of nonoperative treatments in
      conjuction with relevant specializations.

PMID- 9574136
TI  - [Surgical information systems as instruments in quality assurance].
AB  - In various aspects, it is important to document medical procedures performed in
      surgical management. These records have become even more relevant because, in
      realizing the German health structure law, new forms of remuneration have been
      established, which are correlated with defined services. This means that data
      from medical documentation records today "rule" on financial compensation and,
      consequently, on the total economy of a hospital. Data are to be gathered
      considering multiple clinical and administrative requests; they have to register
      all pre-, intra- and postoperative details in their complex correlations; and,
      they are subject to strictly limited periods of compulsory availability. To meet
      these demands, data can only be recorded and evaluated by adequate computerized
      information systems. Starting out from a general data profile in response to
      questions from inside and outside of the hospitals, general criteria will be
      presented on what is to be recorded and how data are to be structured by surgery
      information systems. We will also refer to the interfaces required with
      information systems of other clinical departments that are part of the overall
      hospital information system. On this basis, guidelines are set up on how to plan,
      select, introduce and efficiently run these systems.

PMID- 9574137
TI  - [Guidelines in minimal invasive surgery in oncologic thoracic surgery].
AB  - Due to the development of video-assisted thoracoscopic surgery (VATS) over the
      past 7 years, many procedures are now technically feasible. A side from
      indication in benign disease, VATS became important for the presectional staging
      of lung cancer, the biopsy of pulmonary lesions and extrapulmonary intrathoracic
      tumors, wedge resections of isolated pulmonary nodules and the treatment of
      pleural or pericardial effusions, as pleurodesis and pericardial window. The
      current status of VATS metastasectomy, lobectomy and pneumonectomy is
      controversial and there are no clear indications for VATS lobectomy or
      pneumonectomy.

PMID- 9574138
TI  - [Perspectives in applying guidelines].
AB  - Definition, purpose and future fate of guidelines are presented. Special stress
      is placed on the fact that guidelines represent a tool for rationalization by
      which economical capacities are activated and rationing is prevented.

PMID- 9574139
TI  - [Internal quality assurance--Munster experiences].
AB  - Medical data monitoring is an effective tool to insure high quality and efficient
      performance of health care providers. In the Department of Thoracic and
      Cardiovascular Surgery of the University of Muenster this is based on a
      comprehensive data management system. This system has been custom tailored to
      enable optimal monitoring of quality, performance and cost aspects based on
      access to all available data. Data acquisition is achieved online and allows for
      continuous data analysis. This data monitoring is the basis for objective quality
      control of medical performance as well as for the evaluation of the impact of
      politically induced economic restrictions on the quality of care.

PMID- 9574140
TI  - [Internal quality assurance or Hawthorne effect?].
AB  - The tendency of study participation per se to affect outcome is described by the
      term Hawthorne effect. This process defines the first step for internal quality
      assurance. However, whenever an attempt is made to describe the effects of
      quality assurance in more detail specific mathematical tools are required,
      including a database system that allows the calculation of clinical profiles,
      problem profiles, time-related variance of variables, univariate and multivariate
      statistics, calculation of scores and application of the hazard function.
      However, it has to be considered that any mathematical model is a way to present
      a hypothesis and not a proof. Whenever a proof is required, one should not ask
      for internal quality assurance, but design a randomized study.

PMID- 9574141
TI  - [Basic surgical research as an interdisciplinary responsibility].
AB  - Surgical research starts with a disease or a clinical problem of the surgeon's
      and the research has the benefit of the patient as its ultimate goal. Basic
      surgical research, in agreement with this task, must therefore be defined as
      biomedical and clinimetric research. The problem determines the approach. Basic
      surgical research, therefore, is interdisciplinary; it forms a bridge between
      basic science and the clinic. Surgical research compared with other medical
      disciplines, however, is not well funded by current programs of official grant
      giving organisations, such as DFG and BMBF. To encounter this deficiency, it is
      mandatory to support existing concepts of successful surgical research, such as
      institutes/departments of surgical research and theoretical surgery.

PMID- 9574142
TI  - [Regionalization of surgical research in Germany].
AB  - Surgical research can only be effective if there is good cooperation between
      clinical and basic researchers. Surgeons should be given the opportunity to
      practise surgical research as a full-time job for several years. We present part
      of the data obtained from all surgical departments of German universities
      concerning the organisation of their surgical research.

PMID- 9574143
TI  - [Molecular diagnosis and therapy in surgery].
AB  - Efficiency and economy is surgical research exemplified in molecular diagnostics
      and therapy must be looked upon from two view points: 1.) The efficiency of
      molecular diagnostics is relatively easy to assess. It is more difficult to prove
      the therapeutic consequences of new knowledge. To achieve this, long-term
      observations for 3-5 years are necessary. This fact underlines the difficulties
      in clinical research linearly consuming more time and efforts compared with basic
      research. Economists in surgical research must pursue the aim to bring a
      procedure to clinical application having it financed by the insurance companies.
      This involves a long-term approach. Several financing schemes are included in a
      step-wise approach: Third parties for basic research, resources for clinical
      studies from the appreciate institutions, co-operation with industrial partners
      for the evolving clinical application and lastly the clinical recognition by the
      health care organisations.

PMID- 9574144
TI  - [Value of clinical research in Germany in an international comparison].
AB  - Clinical research in Germany, compared with other countries, is not well off.
      There is enough evidence showing that German speakers in international
      conferences are underrepresented as well as German authors in international
      (English-speaking) journals. There are a multitude of reasons why this is so. The
      main problem is an overwhelming clinical workload in university hospitals, which
      does not allow enough time to be saved for research. There is obviously no lack
      of money for research and development.

PMID- 9574145
TI  - [Surgical epidemiology].
AB  - The application of epidemiological principles and methods to problems in surgery
      (Surgical Epidemiology) still plays a minor role in Germany. Different examples
      are presented, demonstrating that an increase of intellectual power can be
      achieved by applying epidemiological methods to surgery. Future developments in
      surgery can be estimated and the role of surgery in comparison with other
      clinical disciplines can be clarified and strengthened. Similar to foreign
      countries, support of Surgical Epidemiology by reference centers is required.

PMID- 9574146
TI  - [Clinical research. Socioeconomic factors exemplified by endoscopic surgery].

PMID- 9574147
TI  - [Evaluation models for therapy planning/standardization exemplified by
      infection].
AB  - Models of evaluation in therapeutic management pathways (practice guidelines,
      clinical algorithms) are demanded today, both by public health research and
      health policy. However, practical achievements are lacking. To overcome this
      controversy, the Lucerne Study Group on Sepsis Research was founded to develop
      guidelines in accordance with a series of official groups. It was shown that
      there was no agreement between the providers and the daily users. However, every
      surgeon has a firm, personal view about sepsis.

PMID- 9574148
TI  - [Evaluation and quality management in multiple trauma care].
AB  - In total quality management of polytraumatised patients, it is necessary to use
      analysis of structure, process and outcome quality to search for problem areas
      and improvement possibilities. The structure includes the attributes of material
      and human resources. The process denotes the real treatment course with the
      demand for treatment guidelines (algorithm) and an exact documentation of
      treatment. To prove the outcome quality, an internal and external judgement is
      possible. Our own results show that quality assessment, concerning the process as
      well as the internal and external quality outcome, brings a significant
      improvement to the care of polytrauma patients.

PMID- 9574150
TI  - [Promoting research from the viewpoint of health insurance].

PMID- 9574149
TI  - [Promoting research from the viewpoint of the German Research Society].
AB  - The Deutsche Forschungsgemeinschaft (DFG) serves all fields of sciences and the
      arts by financing research projects. The DFG can support science by funding of
      individual grants, priority programmes, research groups and collaborative
      research centers. With these mechanisms of funding, clinical research is also
      supported. Some structural aspects of clinical research and a few thoughts for
      the improvement of clinical research are presented.

PMID- 9574151
TI  - [Surgical oncology: possible methods for financing complex oncological therapy
      procedures].
AB  - The AOK Schleswig-Holstein actually finances the evaluation of treatment costs
      for the project "Operative Oncology". After the primary conceptual phase, the
      project will be financed for several years and will be accompanied by quality
      control studies. In addition to the procedure of the BMG, the costs of
      psychological support/therapy as well as for new molecular biological tests for
      the detection of micrometastases are calculated. The reason for this calculation
      is that these additional costs might be included into a specific, oncological
      resource-based value system of payment.

PMID- 9574153
TI  - [Research cooperation with industry from the viewpoint of surgery].

PMID- 9574152
TI  - [Promoting research from the viewpoint of industry].
AB  - Industry sponsors medical research in the fields of pharmaceutical products,
      diagnostics, medical technology, medical equipment, clinical nutrition and
      information systems. In pharmaceutical research, the companies of VFA invested a
      total of DM 4.3 billion in 1995, that means 18% of the turnover. DM 1.4 billion
      were spent mainly on clinical research studies. Beyond this, industry shares the
      costs of academic research institutes and gives support through its foundations.
      The decreasing number of domestic clinical studies, that German clinics complain
      about, is caused by organisational and administrative deficiencies, leading to
      major economic disadvantages. Recommendations of how to improve the situation
      exist and must be implemented.

PMID- 9574154
TI  - [Between bench and bedside: examples of clinically oriented basic surgery
      research].
AB  - Animal experimental studies are an effective modality for testing new therapeutic
      strategies, provided that the animal model and the study protocol simulate the
      clinical situation. This is exemplified by various animal experimental studies on
      the therapy of infectious complications in acute necrotizing pancreatitis that
      were performed preliminary or supplementary to clinical studies. The results show
      that basic surgical research with close clinical orientation can be usefully and
      fruitfully combined with clinical studies and enables the academically active
      young surgeon to overcome the dualism between laboratory work and clinical
      practice.

PMID- 9574155
TI  - [Surgical research and publications in Germany--an analysis of 1984-1994].
AB  - The present study analyses a selection of German and American surgical and cancer
      research journals from the years 1984 and 1994. The aim of the study was to
      evaluate the amount of publications by German surgeons in these journals.
      Furthermore, any influence of the impact factor on the publication criteria was
      analyzed. German surgical journals showed a high percentage increase in the
      impact factor but are, in absolute numbers, still significantly behind the
      American journals. In parallel, German surgeons are still the major contributors
      to German language journals, but increasingly publish in the American ones as
      well. The impact factor is one of the major selection criteria on to which
      journal a paper shall be submitted.

PMID- 9574156
TI  - [Surgical research with limited resources: research concepts and research
      cooperation in a surgical University Clinic].
AB  - The decreasing financial support of surgical research requires new strategies
      and, in particular, an intensive collaboration with basic science and
      biotechnology. This concept of "lean research" includes output-orientated
      research activities, which can be measured, using the "impact factor". Effective
      research requires a well-organized and structured department.

PMID- 9574157
TI  - [Regional cooperation in molecular biology topics].
AB  - Research on rare events, such as the occurrence of port-site metastases, can be
      speeded up by pooling patients from different hospitals. Multidisciplinary
      approaches, involving surgeons, pathologists and molecular biologists, allow more
      detailed experimental results to be obtained. Research costs are kept low by
      using existing infrastructures over a short period of time.

PMID- 9574158
TI  - [Increased incidence of adenocarcinomas in the esophagus and cardia--effect of
      epidemiologic data on developments in surgery].
AB  - Results of this study show an increasing incidence of adenocarcinoma in the
      esophagus and cardia. The reasons of this rise are speculative. Adequate
      diagnostic and therapeutic strategies must be evaluated; these can only be
      performed in specialist centers.

PMID- 9574160
TI  - [Instrumental diagnosis for therapy decision making--what is possible and
      desirable, what is indispensible and what is superfluous in tumors of the
      pancreas?].
AB  - The spectrum of diagnostic procedures in patients with pancreatic malignancies
      today includes the patient's report and history, laboratory parameters, and
      modern techniques ranging from ERCP, EUS, CT, angiography, MRCP, and PET to
      molecular biology and parameters such as the cytological detection of ki-ras
      mutations. Anamnesis, laboratory parameters, tumor markers, ultrasound
      investigation, and ERCP are the relevant procedures for establishing the basic
      diagnosis of a pancreatic malignancy. MRCP will replace ERCP in most cases in
      future. EUS shows the highest accuracy in the diagnosis of vascular involvement
      by a pancreatic tumor.

PMID- 9574159
TI  - [Changes in the epidemiological parameters of radiation-induced illnesses in East
      Hungary 10 years after Chernobyl].
AB  - Ten years after the Chernobyl fall-out, a significant increase was found in the
      number of childhood and adolescent papillary thyroid carcinomas (p < 0.05) and
      Hashimoto thyroiditis (p < 0.01) among the 1226 thyroid patients operated on at
      the 1st Department of Surgery of the University Medical School of Debrecen.

PMID- 9574161
TI  - [Instrumental diagnosis and therapeutic decision making in biliary surgery].
AB  - Preoperative evaluation before cholecystectomy includes detailed history of the
      disease and blood chemistry. Hepatobiliary ultrasonography is the main
      noninvasive preoperative investigation. The decision to evaluate the common bile
      duct for stones prior to planned laparoscopic cholecystectomy by ERC may be
      prompted by clinical suspicion or evidence of jaundice, recent pancreatitis, or a
      dilated common duct on sonography. Preoperative ERC has the advantage of allowing
      the simultaneous treatment of duct stones. Intraoperative cholangiography should
      be available.

PMID- 9574162
TI  - [Instrumental diagnosis for therapeutic decisions--what is possible and
      desirable, what is essential and what is superfluous--in goiter surgery].
AB  - In addition to patient history and clinical examination, the basis of thyroid
      diagnosis consists of bTSH measurement and ultrasound to provide information on
      function and morphology. Solitary nodules have to be differentiated into "cold"
      and "hot" by scintigraphy. For cold nodules, FNA cytology is strongly
      recommended. Immunogenic hyperthyroidism is proven by positive TRAK measurement.
      Thyroidal autonomy requires suppressive scintigraphy for morphologic guidance.
      Special imaging procedures like CT and MRT are reserved for special situations of
      retrosternal extension.

PMID- 9574163
TI  - [Instrumental diagnosis for therapy decision making--what is possible and
      desirable, what is essential and what is superfluous--in breast surgery].

PMID- 9574164
TI  - [Instrumental diagnosis for therapeutic decision making in retroperitoneal
      tumors].
AB  - In cases of retroperitoneal soft tissue tumors, individual diagnostic strategies
      should be chosen. In adrenal gland neoplasias, diagnosis is mainly based on
      clinical evaluation including ultrasonography, hormone tests, and computed
      tomography. Magnetic resonance imaging, scintigraphy of the adrenal medulla, and
      selective adrenal vein sampling are indicated in selected cases. Other procedures
      are not necessary.

PMID- 9574165
TI  - [Instrumental diagnosis for therapy decision making--what is possible and
      desirable, what is essential and what is superfluous--in vascular surgery].
AB  - It is impossible to give a paper on the whole of vascular surgery, which
      represents a broad surgical specialty; so we will concentrate on three typical
      vascular procedures, namely Carotid surgery, abdominal aortic aneurysm, and
      varicose veins. Ultrasound examinations in carotid artery disease are inevitable
      because they are screening examinations. CCT or MRT are necessary, but not
      angiography, particularly in symptomatic patients. In asymptomatic patients, DSA
      may be of value for forensic documentation; MR angiography is now better, but is
      still not so evident as conventional DSA. CBF should be carried out in multiple
      vessel disease. Intraoperatively, quality control can be assured by Doppler or
      flowmetry; other techniques like DSA, EEG, SEP or transcranial Doppler are not
      necessary when a temporary shunt is routinely applied. In AAA, sonography and CT
      (or MRT) are absolutely necessary; angiography may reveal accessory visceral and
      renal vessels. In treatment of varicose veins, sonography (color-coded) is
      indispensible; phlebography can reveal more details, but is not absolutely
      necessary.

PMID- 9574166
TI  - [Instrumental diagnosis for therapy decision making in abdominal injuries].
AB  - The aim of diagnostic procedures following abdominal injuries is rapid assessment
      of the necessity for surgical intervention and specification of the organ lesion,
      thus reducing the number of negative laparotomies. The extent of the diagnostic
      approach must be reduced in unstable patients. Sonography is the standard
      procedure in stable as well as in unstable patients, both in the initial period
      and the subsequent follow-up. CT-scan is complementary to sonography in detecting
      organ lesions. Sonographically guided puncture has replaced diagnostic peritoneal
      lavage. Laparoscopy following blunt abdominal injuries is not useful; however, it
      may be helpful following penetrating abdominal trauma.

PMID- 9574167
TI  - [Instrumental diagnosis for therapy decision making--what is possible and
      desirable, what is essential and what is superfluous?].
AB  - With knowledge of the classical radiological characteristics of benign and
      malignant bone tumors, taking age and localization of lesion into consideration,
      and with the help of classification according to Lodwick, 90% of all cases can be
      diagnosed. Compared with benign lesions, malignant tumors are quite rare, so
      those with less experience are advised--in case of doubt--to carry out a
      reference evaluation, since further imaging, e.g., costly magnetic resonance
      imaging (MRI), is in general not of any help for diagnosis. Only when malignancy
      is suspected or to plan biopsy is MRI, however, not only desirable to outline the
      malignant lesion in bone and soft tissue, but is an absolutely necessary in
      modern interdisciplinary treatment concepts, without which extremity-conserving
      surgery with constantly increasing life expectancy together with the considerable
      success of chemotherapy would be unthinkable.

PMID- 9574168
TI  - [Instrumental diagnosis and therapy decision making--ultrasound diagnosis and
      interventional measures].
AB  - Therapeutic decisions based on ultrasonographic findings afford a high accuracy
      of the diagnosis. Adequate equipment in the department and appropriate training
      of the surgeon are essential prerequisites. It is desirable to have possibilities
      of application which go far beyond routine ultrasonography of the abdomen. It is
      possible to develop a highly specialized ultrasonography which, however, becomes
      unnecessary if the question can more definitely be decided by computed tomography
      or magnetic resonance imaging.

PMID- 9574169
TI  - [Magnetic resonance tomography and interventional measures].
AB  - In contrast to conventional radiography or ultrasonography, magnetic resonance
      imaging (MRI) is influenced by different factors. As a consequence, tissues and
      fluids can be visualized using different techniques. Obviously MR imaging has a
      lot of advantages, but only a small number of disadvantages and
      contraindications. Without using X-rays, interventions can be done under real
      time MR control. An open-configuration MR-system allows vertical access to the
      patient during interventions. The combination of laparoscopy and MR imaging
      enables the surgeon to observe organ surfaces as well as parenchymal structures
      at the same time. Depending on the high temperature sensitivity of MR imaging,
      this technique can be used to guide interstitial laser therapy or cryosurgical
      interventions.

PMID- 9574170
TI  - [Rational diagnosis in primary and recurrent pheochromocytoma].
AB  - Measurement of urine and plasmacatecholamines allows reliable diagnosis of
      primary and recurrent pheochromocytoma. Chromaffin tumors which are thereby not
      identified may safely be operated upon without preoperative high-dosage
      phenoxybenzamine. In more than 80% of patients, ultrasonography suffices for
      localizing adrenal pheochromocytoma as well as paraganglioma. CT or MRI may be
      helpful when malignancy is suspected. Venous catheterization and sampling is only
      indicated when other diagnostic procedures fail to identify the source of a
      proven hypersecretion of catecholamines, and thus adrenal hyperplasia is
      suspected.

PMID- 9574171
TI  - [Effect of modern instrumental diagnosis on surgical indications for resection of
      colorectal liver metastases].
AB  - In order to select those patients with colorectal liver metastases who may have
      benefit from an operation, preoperative detection and localization of tumors in
      the liver is necessary. In this study, the specificity and sensitivity of a CT
      arterial portography and magnetic resonance imaging with contrast media was
      compared with the results of operative findings and intraoperative
      ultrasonography. The combination of both preoperative methods led to an accuracy
      rate of more than 90%, and all patients who underwent laparotomy were resected or
      treated with an arterial infusion port system. Negative laparotomies were
      excluded completely.

PMID- 9574172
TI  - [Value of color Doppler ultrasound in preoperative planning of the resection of
      liver tumors].
AB  - New color Doppler sonography with high resolution improves the detection of liver
      tumors and provides better information on the hepatic vessels. Echo contrast
      agents which pass through the lungs open up new fields of application in the
      investigation of blood flow.

PMID- 9574173
TI  - [Ultra-rapid magnetic resonance tomography: a quantum leap in preoperative
      hepatobiliary diagnosis?].
AB  - The recent improvements in magnetic resonance (MR) imaging using the new
      ultrafast echo-planar technique for diagnosis of hepatobiliary lesions are
      outstanding. Besides the detection and preoperative evaluation of benign and
      malignant hepatobiliary tumors, angiography and cholangiography can be
      simultaneously performed using the techniques of MR angiography or MR
      cholangiography. Looking ahead, further advantages such as three-dimensional
      image reconstruction, no X-ray exposure, and short examination time, this MR
      technique will become the preferred diagnostic procedure for evaluating
      hepatobiliary lesions.

PMID- 9574174
TI  - [A method for nidus localization in osteoid osteomas].
AB  - A method for localization of the nidus of osteoid osteomas using CT-controlled
      needle placement and subperiosteal marking with methylene blue is demonstrated.
      Our clinical experience in 13 patients is reported. This method allows proper
      intraoperative localization of the nidus of osteoid osteomas without problems.
      Thus, osseous resection can be reduced and additional stabilization by internal
      fixation or defect filling by bone graft are not necessary.

PMID- 9574175
TI  - [Use of improved magnetic resonance tomography in vascular surgery with reference
      to efficiency and economy].
AB  - The technique of Gadolinium-enhanced MR-angiography has become much better over
      the past year. The quality of the method is equal to conventional angiography.
      The advantages of MRA in comparison to conventional angiography today are: less
      strenuous for the patient, faster, CT or ERCP can be saved, MRA can be more
      economic.

PMID- 9574176
TI  - [Value of preoperative angiography in surgery of the hemodialysis shunt].
AB  - Contrast angiography is still very important in evaluating the luminal anatomy of
      failing shunts and their venous runoff systems prior to intervention or surgical
      revision. For access monitoring, prior to primary AV fistulas or in case of a
      thrombosed access, angiography can be replaced by less invasive methods (physical
      examination, pressure measurements, color-flow doppler).

PMID- 9574177
TI  - [Detection of the hemodynamic effects of renal artery stenosis with MRI flow
      measurement].
AB  - Data derived from the MR-CINE phase-contrast flow measurement of renal arteries
      correlates well with the angiographically detected degree of stenosis and
      scintigraphic measurements. MR data permit the quantitative analysis of altered
      hemodynamics and MR is a non-invasive substitute for angiography preoperatively
      and during follow-up. Angiography is indicated only for the evaluation of
      morphological criteria.

PMID- 9574178
TI  - [Instrumental diagnosis for therapeutic decision: intra-arterial DSA versus 3D CT
      angiography in abdominal aortic aneurysms].
AB  - Compared to intraarterial DSA, 3D spiral CT-angiography could be an reliable
      alternative method for preoperative evaluation and planning of abdominal aortic
      aneurysms. 3D data reconstruction with new rendering techniques (especially
      "volume rendering") provides unique information about mural thrombus, calcified
      plaques, vessel kinking and renal/visceral arteries. However, the more invasive
      intraarterial DSA should be performed in patients with complex occlusive disease
      of the iliac arteries, renal or visceral artery stenoses, or pathological
      findings in peripheral duplex sonography or if intraluminal exclusion with
      endostent placement is planned.

PMID- 9574179
TI  - ["Necessary" diagnostic procedures in traumatic aortic rupture, acute dissecting
      and chronic aortic aneurysms].

PMID- 9574180
TI  - [Computerized tomography of the thorax as a decision aid in intensive care of
      blunt thoracic trauma].

PMID- 9574181
TI  - [Blunt thoracic trauma--therapeutic relevance of results of roentgen image,
      ultrasound and computerized tomography].
AB  - In 60 patients with severe thoracic trauma the diagnostic procedures--X-ray of
      the chest, sonography and thoracic computed tomography (CT)--were reviewed for
      their incidence of finding all injuries. X-ray of the chest often failed to
      detect lung contusion and injuries in the mediastinal space. Four of five
      ruptures of the diaphragm were incidental findings on the occasion of laparotomy
      because of intraabdominal bleeding.

PMID- 9574182
TI  - [Technology assessment of ultrasound in acute diagnosis of blunt abdominal
      trauma].
AB  - In this article a systematic technology assessment was used for ultrasound in
      blunt abdominal trauma. We found sonography to be a simple, fast and complication
      free method with high sensitivity and specificity. Ruptures of the small bowel
      seemed to be extremely difficult to detect, especially in the early phase after
      blunt abdominal trauma. No basic definitions of significant free fluid and
      maximal limit for non-operative treatment are found in the international
      literature. Only the combination of prognostic factors such as mechanism of the
      accident, clinical examination, and the intuition of the surgeon leads to a
      decision.

PMID- 9574183
TI  - [Value of endosonography in tumors of the upper GI tract in comparison with
      different scanners (Radial 360 degrees and Sector Scanner 120 degrees].
AB  - This comparative study was performed to determine the value of two endosonography
      devices, i.e, the radial and the longitudinal transducer, for staging upper GI
      tract cancer. The accuracy of both methods was comparable in esophageal cancer,
      whereas radial scanning was superior in gastric cancer. Generally radial scanning
      provided better spatial orientation and was easier to assess. An advantage of the
      longitudinal curved array scanner is the feasibility of EUS-guided biopsy.

PMID- 9574184
TI  - [Preoperative staging of stomach carcinoma with endosonography--fact or fancy?].
AB  - From January 1993 till December 1995, a total of 116 consecutive patients with
      gastric carcinoma were evaluated with endosonography and the results were
      compared with the histology of the resected specimen. The accuracy rate of the
      endosonography was 80% for T1 tumors an 83% for T4 tumors, and the sensitivity
      and specificity in the detection of regional involved lymph nodes were 91% and
      84% respectively. Therefore endosonographic staging alone ist not a valuable
      pretherapeutic procedure to decide about endoscopic therapy in limited and
      neoadjuvant chemotherapy in extended gastric carcinoma.

PMID- 9574185
TI  - [PET in pancreatic tumor of unknown origin--luxury or value?].
AB  - 18FDG-positron emission tomography (PET) was performed preoperatively in 159
      patients (89 pancreatic cancers, 48 inflammatory pancreatic tumors, 22 benign
      tumors) with pancreatic mass of unknown origin and its diagnostic value (ROC
      analysis) was compared with ERCP and computed tomography. In patients with normal
      fasted blood glucose level (< 130 mg%) and without active inflammation (n = 126),
      diagnostic value of PET was equal to ERCP (0.94) and higher than CT (0.84; p <
      0.02); PET showed in 88% of cases no prediction of resectability or local tumor
      infiltration, no influence on explorative celiotomies, in 93% no increase of
      preoperative hospital stay, in 4% influence on surgical strategy, in 5%
      metastases as additional information. Though its additional information gain for
      the surgeon remains limited, PET is certainly a diagnostic achievement with high
      diagnostic value in preselected patients.

PMID- 9574186
TI  - [Efficacy and economic aspects of preoperative diagnosis: laparoscopy is useful
      in only 13% of patients with pancreatic carcinoma].
AB  - The value of diagnostic laparoscopy to improve tumor staging in patients with
      pancreatic and periampullary cancer is still a matter of controversial
      discussion, especially with regard to whether diagnostic laparoscopy can identify
      patients in whom a laparotomy can be avoided due to metastases. To answer this
      question, all patients who underwent operations for pancreatic cancer (n = 97) or
      periampullary cancer (n = 30) between 11/1993 and 12/1995 were evaluated. Only
      10% of the patients with periampullary/pancreatic cancer and 13% with pancreatic
      cancer could avoid laparotomy through diagnostic laparoscopy. Due to these low
      numbers, a diagnostic laparotomy cannot be recommended in general in patients
      with pancreatic and/or periampullary cancer on economic grounds and because of
      the risk of trocar metastases.

PMID- 9574187
TI  - [Endosonography, CT and MRI in the diagnostic concept of rectal carcinoma].
AB  - The stage-adapted operative treatment of rectal cancer in the context of adjuvant
      therapy regimes necessitates accurate and, in times of diminishing financial
      resources, cost-effective preoperative staging. From January 1988, 424 patients
      with rectal cancer were examined by endosonography. In the same period 28
      additional patients were staged by hydro-CT within a prospective study as the
      endorectal sonography probe could not be passed through the tumor stenosis.
      Sensitivity and specificity for T and N staging were equal or superior in the
      endosonography group. Compiled data in the literature for MRI staging of rectal
      cancer show results similar to those with endosonography. Therefore we see no
      indication for preoperative rectal staging methods other than endosonography
      unless the latter examination is technically impossible.

PMID- 9574188
TI  - [Preoperative instrumental diagnosis of rectal carcinoma. Value of various
      methods with reference to therapeutic decision making].
AB  - A retrospective analysis of 238 patients with rectal cancer undergoing primary
      surgery was performed in respect of preoperative diagnostic examinations. It is
      shown that stage-adjusted therapeutic approaches (e.g. peranal rectal excision,
      preoperative radiotherapy, or palliative surgery) can be pin-pointed with a high
      degree of certainty using colonoscopy, endorectal ultrasound and abdominal
      ultrasound. With the possible exception of selected patients with far-advanced
      rectal cancer there is no need for intravenous pyelography or computed tomography
      of the abdomen or lower pelvis.

PMID- 9574189
TI  - [Pyogenic infections of the skin and skin appendages].
AB  - In Germany more than 120,000 soft tissue infections are treated in hospital per
      year. Articles about soft tissue infections caused by Strept. pyogenes, presented
      in the lay press as "flesh-eating bacteria", accentuate this picture. Among these
      soft tissue infections, necrotising fasciitis and the associated "toxic shock
      syndrome" and "toxic shock-like syndrome" remain a challenge to the surgeon. The
      most important role of surgery is to achieve the right diagnosis and introduce
      definitive therapy in time. Central to surgical therapy is immediate incision and
      open drainage. Our own experience in animal models underlines the important role
      of abscess pressure and physicochemical parameters in the "abscess compartment"
      for systemic spread. Based on this pathophysiological background, the traditional
      "ubi pus ibi evacua" has lost nothing of its importance.

PMID- 9574190
TI  - [Recurrent sweat gland abscess].
AB  - Hidradenitis suppurativa is of high clinical and social significance,
      particularly if appearing as symptom of acne inversa and if located in the
      genitoanal region. Successful treatment includes early diagnosis together with
      thorough surgical therapy. The latter consists of wide local excision in order to
      remove all infected tissue. Localization and the size of defect as well as the
      experience of the surgeon predict the method of plastic reconstruction. Non
      surgical procedures are only of supporting character either prior to or after
      surgery.

PMID- 9574191
TI  - [Olecranon and pre-patellar bursitis].
AB  - Olecranon and prepatellar bursitis have a prevalence of 3 in 1000 patients; the
      predominant etiology is a traumatic lesion with or without inoculation of
      infectious material, mainly during professional or leisure activities. Separation
      into septic and non-septic bursitis is possible in most cases according to
      clinical parameters and characteristics of the contents of the affected bursa.
      The therapy of acute and chronic bursitis is guided mainly by the nature of the
      aspirate retrieved from the bursa: a serous content justifies conservative
      treatment with compression, immobilization, antiphlogistic medication, and (in
      selected cases) the instillation of corticosteroids; a purulent aspirate
      necessitates bursotomy with incision and drainage, or bursectomy. Only in
      selected cases is a conservative trial with antibiotics, immobilization, and
      antiphlogistic medications justified.

PMID- 9574193
TI  - [Fournier gangrene].
AB  - Fournier's gangrene is a rapidly spreading soft tissue infection. Applying our
      main principles of therapy to the four patients we have treated in the past 4
      years, all patients survived. One case report is presented in detail. Early
      diagnosis is essential. CT plays an important role. Aggressive resuscitation,
      daily surgical exploration and debridement remain the key to the management of
      this disease. The prevention of orchidectomy is one of our aims. Faecal diversion
      is seldom necessary.

PMID- 9574192
TI  - [Infected pilonidal sinus].
AB  - During the past 11 years (1985-1996), 324 patients with pilonidal sinus were
      treated. In 272 cases primary wound closure was performed, in contrast to 52
      cases with secondary wound healing. One hundred and fourteen patients were
      additionally treated with an antibiotic carrier (group 1), 158 were not (group
      2). In group 1 primary healing occurred in only 66% of cases vs 69% in group 2.
      We found wound complications with a lag time of 4 days in comparison with group
      2. Serious wound secretion persisted longer in group 1, resulting in a longer
      hospital stay of 6.5 days on average. We conclude that the application of
      antibiotic carriers does not raise the rate of primary wound healing. Better
      results can be achieved by secondary wound healing appropriate treatment with
      hydrocolloidal moist wound dressings.

PMID- 9574194
TI  - [Necrotizing fasciitis].
AB  - Necrotizing fasciitis has changed considerably over time. The disease used to be
      due to group A streptococci and affected otherwise quite healthy or traumatized
      subjects. Today we see multibacterial infections in polymorbid or
      immunocompromised patients. Rapid and resolute surgery is of critical prognostic
      value. Early clinical recognition may be difficult. Sometimes frozen-section
      biopsy proves helpful. Septic immune response and organ failure develop rapidly
      in these patients. After vigorous staged necrosectomy, extensive plastic
      reconstruction is mostly required.

PMID- 9574195
TI  - [Ulcus cruris venosum].
AB  - The conservative treatment of venous crural ulcer is frustrating, and a
      recurrency rate of 25% is seen. Even after surgical treatment of the underlying
      venous disease, long-lasting septic complications and persistent wound infection
      occur. The combination of ESDP, paratibial fasciotomy and vacuum sealing therapy
      is a modern concept of varicose vein surgery. For the first time we are able to
      present a concept of surgery to cure venous crural ulcer definitely within an
      acceptably short period.

PMID- 9574196
TI  - [Infected decubitus ulcer].
AB  - The treatment of pressure sores, which have a high incidence in hospital
      patients, is a long standing problem. Pathogenesis, treatment modalities and the
      results, including long-term follow-up, are discussed. The value of a step-by
      step concept is emphasized, starting with simple procedures like local flap
      rotation up to musculocutaneous flaps. Furthermore, the reconstructive options,
      especially in patients with pressure sores of the sacral and ischial region, are
      presented.

PMID- 9574198
TI  - [Diabetic foot].
AB  - Diabetics suffer from a high rate of amputation. Unclear terminology is partially
      responsible. We offer a clear classification (type A = PAOD; type B =
      polyneuropathy; type C = combination of A + B). Our classification for plantar
      ulcer is simple and yields clear indications for appropriate therapy. The
      operative principles for type B, foot will be discussed (dorsal incision, distal
      two-thirds resection of metatarsals, proper coverage of bones with soft tissues,
      necrectomy, placement of Gentamycin-bonded collagen sponge, drainage, primary
      wound closure, plantar ulcer left untouched). In a collection of 284 treated type
      B diabetic feet, in only 6% of cases was there secondary wound healing. The
      plantar ulcer was always cured.

PMID- 9574197
TI  - [Treatment strategies in bite injuries].
AB  - Animal and human bites are a extremely common problem. Despite the prevalence of
      this problem, few systematic studies have been done. There is astounding sparsity
      of factual information in the literature to aid the therapeutic decision. Crucial
      questions regarding suturing, antibiotics, and other matters have been left
      unanswered. Therefore the literature was reviewed and therapeutic guidelines
      extracted.

PMID- 9574199
TI  - [Infections of the hand].
AB  - Tendon sheath infections and septic arthritis require early irrigation therapy in
      order to avoid permanent loss of function. In the thumb, infection of the sheath
      often leads to an acute carpal tunnel syndrome, necessitating open median nerve
      decompression. Differential diagnoses have to be taken into consideration:
      tuberculous synovialitis of the tendon sheath or finger joint is not yet extinct.
      The severely painful herpetic whitlow of the finger tip requires virostatic
      therapy. Operative measures are also not indicated in the acute calcium deposit,
      which as a rule resolves spontaneously within several days. Only its chronic
      recurrent form with or without pressure symptoms requires surgical intervention.

PMID- 9574200
TI  - [Vacuum dressing in septic wound treatment].
AB  - During the last 2 years, we used the vacuum-sealing technique in more than 300
      patients. We have seen several advantages: clean and sterile wound dressing and
      safe wound healing. In addition, we have used the technique successfully in
      infected areas in combination with alloplastic material. The only problem we
      found is the dependency on operating theatres and a vacuum. We think the
      technique should be recommended for septic wounds in surgery.

PMID- 9574201
TI  - [Surgical wound consultation].
AB  - Treatment of patients with chronic wounds is characterized by high costs and low
      efficiency. Epidemiologic data are mainly based on retrospective studies. In
      1992, we founded a wound care center and developed a diagnostic and therapeutic
      algorithm. Prospective data on 293 patients revealed an overall healing rate of
      68% (diabetic foot syndrome) and 74% (venous stasis ulcer); mean treatment time
      was 4.5 months. Relevant prognostic factors were localization of ulcer (0.004),
      ischemia (0.002), age (0.02) and compliance (0.003), whereas the ulcer grading
      had no effect on healing.

PMID- 9574202
TI  - [Fistula detection in perianal abscess. Prevention or unnecessary trauma?].
AB  - We analyzed our experience with one-stage treatment of anal abscesses and
      fistulae with regard to recurrence and incontinence in a retrospective study
      including 131 patients with a 100% follow-up. It was shown that one-stage
      treatment is safe, not always easy, and that incontinence was associated with a
      high recurrence rate rather than with fistula excision. We conclude that one
      stage treatment by an experienced surgeon is the safest and most satisfactory
      treatment for patients with anal abscesses and simultaneous fistulae.

PMID- 9574203
TI  - [Advancement flap-plasty in perianal fistulas. A reliable procedure in rectally
      normal and Crohn disease patients].
AB  - The endorectal advancement flap is a safe technique for managing anorectal
      fistulas. The recurrence and incontinence rate (fecal soiling) is low. In Crohn's
      fistulae in a noninflammatory period, the results are also equivalent.

PMID- 9574204
TI  - [Streptococcal toxic shock-like syndrome"--a rare complication of pyogenic skin
      infections].
AB  - In recent years there is an increasing incidence of streptococcal toxic shock
      like syndrome in otherwise healthy adults. It is characterized by feaver, rash,
      hypotension and early shock with consecutive organ failure and a mortality rate
      of about 30%. Only early, aggressive and repeated surgical debridement can reduce
      the bacterial load and decrease circulating exotoxins and thereby in combination
      with antibiotic therapy decrease the high mortality of this entity.

PMID- 9574206
TI  - [Is pyodermia fistulans sinifica of clinical importance?].
AB  - Pyodermia fistulans sinifica is a retention dermatopathy. We report on 12 men and
      2 women with this disease, and our radical surgical treatment. The prognosis is
      favourable.

PMID- 9574205
TI  - [Clostridium myonecrosis as a sequelae of intramuscular injections--description
      of 3 fatal outcomes].
AB  - In three fatal cases of clostridial myonecrosis, the following criteria were
      found: repeated intramuscular injections over several years with anti
      inflammatory substances, delay in diagnosis in outpatient care, and following
      uncontrollable systemic septic complications, despite radical surgical treatment.
      Only early, aggressive surgical interventions can stop the rapid course of
      necrotizing soft-tissue infections.

PMID- 9574207
TI  - [Results of early intervention in acute finger infections].
AB  - In the examination of 66 patients treated for acute felons, we classified the
      infections of fingers as (1.) cutaneous/subcutaneous felons; (2.)
      paronychia/subungual felons, (3.) thecal whitlow; (4.) articular/bony felons.
      Primarily, the therapy was based on early aggressive surgical treatment, and
      secondly on antibiotics. With the management described we achieved a good to very
      good result in 76%.

PMID- 9574208
TI  - [Programmed debridement, combined with jet lavage in extensive hand infections].
AB  - 108 patients with a distinct infection of the hand were treated according to a
      protocol with serial debridements in combination with jet-lavage. In 106 patients
      the infection could be controlled with good functional result (79%) and normal
      neurological findings (85%). Microbial count in different tissues showed a
      significant decrease during the serial debridements.

PMID- 9574209
TI  - [Prognostic factors in treatment of diabetic foot ulcers].
AB  - 138 patients with nonhealing diabetic foot ulcers were treated between 1994 and
      1996. Sixty-nine percent of these foot ulcers healed within 17 weeks. Heel ulcers
      had a significantly lower healing rate, probably because of the difficulty of
      taking weight-bearing off this zone. Ischemia also correlated well with low
      healing rates, underlining the importance of vascular diagnosis and surgery.
      Since compliance is the most significant factor for success, it is mandatory to
      educate the patient about his disease and prevent further complications.

PMID- 9574210
TI  - [Diabetic foot--uncontrollable infections despite successful revascularization].
AB  - We treated foot ulcerations in diabetics with limb-threatening ischemia using
      percutaneous balloon dilatation (44) and popliteodistal vein grafts (94). After
      revascularization, we observed in 12% an increase in the infection which
      necessitated major amputation despite open bypass or successful dilatation. A
      diabetic local immunodeficiency leads to cellular and humoral alterations which
      may cause severe tissue damage although the perfusion has been improved.

PMID- 9574211
TI  - [Pyogenic skin infections of the extremities with vascular involvement. Local
      vascular reconstruction and systemic therapy concepts].
AB  - In a 6-year period, we treated 14 patients with severe groin infections involving
      the femoral artery following drug injection in addicts. In 13 cases, we used
      autologous material for arterial reconstruction; in one case of massive bleeding
      the femoral artery had been embolized. Ten patients were treated with full
      success, two patients had claudication postoperatively, and in two cases above
      knee amputations were necessary.

PMID- 9574213
TI  - [Necrotizing fasciitis of the lower extremity].
AB  - Three cases of a necrotizing fasciitis, a rare but life- and limb-threatening
      infection, were treated in the Department of Surgery at the University Hospital
      of the Ruhr University Bochum (MHH) between October 1992 and January 1994. We
      compare our experiences with regard to bacteriological etiology, risk factors,
      localization, and place of entry, course, therapy and mortality with those in the
      literature.

PMID- 9574212
TI  - [Necrotizing fasciitis--a pathophysiological model].
AB  - Real progress in the treatment of necrotizing fasciitis depends on correct and
      early diagnosis. On the basis of our own experience in treatment of 15 patients
      with necrotising fasciitis and on information from the literature, we sketched
      out a pathophysiology model of this sickness. This model centres around local
      thromboembolic ischemia which makes development of a less invasive radiological
      diagnosis possible.

PMID- 9574214
TI  - [Effectiveness and economics of private practice established surgeons,
      exemplified by ambulatory laparoscopic cholecystectomy in 1994 and 1996].
AB  - Ambulatory laparoscopic cholecystectomy is a safe procedure providing high
      patient satisfaction if performed by an experienced surgeon. These are the
      results of a prospective documentation of 150 outpatients to undergo laparoscopic
      cholecystectomy between 1994 and 1996. Patients returned to work early (mean 13.2
      days off). No patient had to be admitted to hospital following ambulatory
      operation. All patients declared that they would have the operation performed in
      the same way a second time if necessary at all. Looking at the money earned for
      the ambulatory operation compared to the costs, there is a deficit of nearly DM
      800 with each performance. Despite the good results and the great satisfaction on
      the part of the patients, outpatient laparoscopic cholecystectomy will not be
      widely performed until and unless the surgeons costs are at least covered.

PMID- 9574215
TI  - [Is ambulatory surgery at a maximum care clinic justified?].
AB  - It is politically desirable to promote ambulatory surgery in private practice or
      in hospitals as a means to reduce costs. In contrast to this, one has to deal
      with unsatisfactory net profits. Even if a hospital is primarily running at a
      loss, ambulatory surgery should be performed. Offering the service of ambulatory
      surgery can improve the recruitment of patients and may help to compete with
      other hospitals.

PMID- 9574216
TI  - [Efficacy and economics of ambulatory surgery in the hospital].
AB  - Ambulatory surgery in the hospital does not reduce the number of hospital beds.
      Available cases are rare. Patients eligible for office-based surgery are mostly
      already operated in offices and larger outpatient units. The legal situation
      regarding postoperative responsibility is difficult. The fees for ambulatory
      surgery are low and represent no incentive for hospitals and doctors.

PMID- 9574217
TI  - [Analysis of surgical performance and diagnostic spectra in general practice].
AB  - The role of surgery in general medicine education is evaluated. To ensure good
      surgical qualification in general medicine, teaching is advised in the
      outpatient, emergency-room and inpatient contexts.

PMID- 9574218
TI  - [Lichtenstein ambulatory inguinal hernia operation].
AB  - The Lichtenstein tension-free hernioplasty is reported. The benefit of costs in
      ambulatory surgery as well as a low complication rate and 0% recurrence rate is
      emphasized.

PMID- 9574219
TI  - [The Lichtenstein inguinal hernia-plasty: a simple and complication-free
      technique, especially suited for ambulatory surgery].
AB  - A consecutive series of 353 patients who underwent Lichtenstein mesh repair for
      inguinal hernia from the 1st of July 1994 to the 30th of July 1995 were studied.
      We analysed our indication, technique, complications, follow-up and outcome.
      Special consideration was given to the advantages and acceptance of day-case
      surgery. Our results suggest that the Lichtenstein repair should be considered as
      a new standard procedure, especially outside of hernia centres.

PMID- 9574220
TI  - [Brief interdisciplinary oncology: a model for ambulatory, multimodal treatment
      of tumor patients].
AB  - Since 10/1994 the Interdisziplinare Kurzzeit-Onkologie (IKO) is an outpatient
      department for the treatment of patients with cancer used by the departments of
      hematology/oncology and surgery. Between 09/1995 and 02/1997, 818 patients
      received 2024 cytotoxic therapies with neoadjuvant (15%), adjuvant (65%) or
      palliative (20%) intention-mostly within multicenter clinical studies. Ambulatory
      operations like removal of lymph nodes for diagnosis or the implantation of
      venous catheter systems prepared the way for specialized modalities of cancer
      therapy. The high compliance and consent of patients, combined with better
      understanding of cancer therapy, resulted in an enhanced quality of life and
      optimized therapy. Standardization in diagnostics and fast realisation of
      interdisciplinary treatment schedules lead to reduction of costs and to
      enhancement of quality and security in cancer therapy.

PMID- 9574221
TI  - [Ambulatory surgery in the hospital: decision between national health insurance
      responsibility and personal job security].
AB  - The aim of outpatient surgery is to reduce costs in the health service. However,
      the number of surgeons working in a surgical department is dependent upon the
      numbers of occupied beds. This creates an existential conflict in which, by
      reducing the occupancy of beds in order to take on more outpatient cases,
      surgeons are putting their own jobs on the line. Possible solutions are here
      discussed.

PMID- 9574222
TI  - [Evidence-based medicine].
AB  - New instruments are required to allocate the available resources to services
      which are not only effective but also beneficial to the patients. These
      instruments are needed to manage the huge amount of new information in medicine
      and to appraise its quality. Evidence-based medicine (EBM) provides these
      instruments to find the relevant literature, to appraise its quality and to merge
      it with the user's clinical experience. EBM is different from "conventionally
      best medicine (CMB)" of four levels; conditions of clinical action, teaching
      goals, medicine at the patient, and goals of continued medical education. We can
      increase our chances to benefit from medical progress if we use these new
      instruments.

PMID- 9574223
TI  - [Possibilities and limits of evaluation research: development of evaluation
      methods with an example].
AB  - Given limited resources in health care, effectiveness and efficiency of medical
      procedures have to be evaluated logically. Rational decision making for resource
      allocation in health care services is based on medical, ethical and economic
      aspects. Systematic observation and query of medical procedures regarding their
      results delivers important data to this discussion. This study on kidney and
      liver transplantation serves as a model, transferable to other domains of health
      care services, and describes the most essential questions of evaluation research:
      When is the medical procedure necessary, reasonable and justified? How can the
      quality of treatment be described and guaranteed? What represents utility in
      quantitative and qualitative terms?

PMID- 9574224
TI  - [Allocation of resources in surgery--the role of waiting lists and scoring
      systems].
AB  - International authors who have applied scoring systems to reduce waiting lists
      conclude that the hope that scoring systems will help is an illusion. Data on
      queue management are extremely rare.

PMID- 9574225
TI  - [Rationalization versus rationing in surgery].
AB  - In the discussion on cost savings in public health, one can differentiate between
      rationalisation and rationing. In this context rationalisation means increase in
      productivity with reduced resources, or more efficient rationing of the available
      means in order to obtain sufficient room for manoeuvre in the public health
      system. By efficient use of the existing resources and adaptation to medically
      appropriate and necessary options one is able to define medical standards for
      treatment. These treatment standards enable the preservation of medical freedom
      of action as well as participation in scientific-technological progress with the
      help of consequent evaluation of treatment patterns. This process could result in
      the development of a so-called priorisation, i.e. active preference of certain
      indications or therapies, which correspond extensively to the expectations and
      priorities of all concerned persons. From the medical point of view explicit
      rationing of health performances has to be strictly rejected.

PMID- 9574226
TI  - [Socioeconomic aspects as the limiting factor].
AB  - Even a health system is no exception to the rule that resources are scarce, i.e.
      only limited financial means are at the disposal of the health sector and thus of
      medicine. Medically sensible possibilities and needs are constantly growing due
      to technological progress, i.e. a deficit occurs between possibilities and needs
      on one hand and financial resources on the other. This leads to a shift in the
      paradigms of medicine, with functional healthcare being the only feasible
      alternative to maximum care due to financial shortage. The scarceness of
      resources thus makes a sparing use of financial means paramount (rationalization)
      and necessitates the insight that not everything that is medically sensible can
      also be realized (rationing). All participants must be prompted by means of
      individual incentives to save costs. It is important that a provision of hardship
      is established for those who are economically weak. Rationing, i.e. the refusal
      of effective measures, should take place by waiting lists without any special
      arrangements for emergencies. Humanitarian reasons do not permit rationing by
      income or age. "Tight" rationing should occur if the chances of third persons
      within the system will thereby be diminished, whereas "loose" rationing would be
      the obvious thing to do, if the system will be relieved because of that.

PMID- 9574227
TI  - [Techniques in teleconsultation].
AB  - The aim of the new developments in telemedicine is to optimize medical care by
      the use of new communication technologies. Teleconsultation is a basic component
      of telemedicine. Telepresence systems demand high-quality video transmissions and
      interactive communication. Comparison of the quality of the transmitted pictures
      demonstrates that an ISDN connection is not suitable for live video
      transmissions. In contrast to this the SICONET/OP 2000 communication module
      allows the setup of an interactive telepresence system with 3D visualization in
      broadcast quality.

PMID- 9574228
TI  - [Data networks in the surgical clinic].
AB  - In the last 5 years, a powerful local area network was established in the
      Surgical Clinic of the Technical University of Munich. It is based on ATM and
      Ethernet technology. About 70 nodes including approximately 100 peripherals in
      our clinic have access to services around this network.

PMID- 9574229
TI  - [Telesurgery: standards--consultations--continuing education].
AB  - The aim of the TESUS project is to bring together several European university
      hospitals in a federation as well as a certain number of clinical centers in a
      network, the purpose of which is the online and offline transmission of surgical
      procedure imaging and advice. The innovation is threefold: It provides the
      surgeon with online information, diagnostic and therapeutic tools and expert
      advice, the need for which might come up before and during surgical procedures,
      as well as the same services in the context of teaching and training through
      regular staff. The developed services will be a major contribution to EU-wide
      standardisation of health care procedures and therapeutic approaches.

PMID- 9574230
TI  - [Costs and potential values of teleconference systems in routine surgery].

PMID- 9574231
TI  - [Concept and realization of nationally applicable clinic guidelines in the intra-
      and internet--a quality assurance measure in the health care system?].
AB  - This project aimed at the realisation of a database for clinical guidelines in
      abdominal surgery and oncology, which can be used within a hospital network as
      well as from the internet. The "Klinikmanual Chirurgie" (currently in German
      only) can be accessed via http://nt1.chir.med.tu-muenchen.de/manual.h tm
      worldwide and free of charge. An English version is in preparation.

PMID- 9574232
TI  - [Establishing a general surgical thesaurus for a speech recognition system for
      electronic data processing assisted surgical report recording].
AB  - Hand-written or manually typed operation reports which are still in use in most
      hospitals are no longer sufficient to handle the ever-increasing amount of
      reports that need to be processed. We developed a thesaurus for general surgery
      to be used within the speech-recognition system ISSS (IBM Speech Server Series).
      From dictation in the operation theatre, the operation report will be generated
      simultaneously in its written form using a fast PC as interface.

PMID- 9574233
TI  - [Use of information systems for direct surgical patient management].
AB  - The aim of this prospective study was to evaluate the use of a modern computer
      based hospital information system for the management of patients in our surgical
      department. The results showed that the information system was well accepted by
      the medical staff and found to be useful throughout daily work. In addition, they
      justify the effort to install and maintain such a system.

PMID- 9574234
TI  - [Rationale and rational tumor after-care from the viewpoint of a community
      hospital].
AB  - After an operation and once discharged, all patients with tumor diseases have to
      receive follow-up medical supervision and therapeutic/chemotherapeutic
      procedures. Tumorstaging and -grading must be considered. All in-patient
      chemotherapeutic treatment for gastrointestinal-, liver-, breast- and thyroid
      gland tumors generally takes place in the surgical department. We are convinced
      that ethical considerations in the treatment of tumor patients are important.

PMID- 9574235
TI  - [Value of individually risk-adjusted after-care--economic management of oncologic
      effectiveness?].
AB  - The individual risk-adapted follow-up programme after R0-resection of colorectal
      carcinoma is a propatiently and favourable alternative. Controlled economic
      studies are required to examine further quantitative and qualitative
      modifications of the follow-up programme.

PMID- 9574236
TI  - [Quality of life parameters in after-care of esophageal carcinoma].
AB  - Thirty-three patients with a radically resected esophageal carcinoma were
      included in a prospective follow-up study measuring quality of life parameters
      under the condition of continuous postoperative out-patient care. None of the
      perioperatively suspected risk factors, like postoperative complications,
      preoperative risk and weight course or a performed thoracotomy had a predictive
      value for the long-term quality of life parameters. Yet endoscopic interventions
      and conservative treatment of dysphagia and eating restrictions improved the
      quality of life in 12 out of 16 patients with severe symptoms, making the
      postoperative follow-up an important factor for the quality of life for resected
      esophageal cancer patients.

PMID- 9574237
TI  - [Is routine tumor after-care after gastrectomy sensible?].
AB  - Only 22.3% of patients with recurrence after potentially curative gastrectomy are
      discovered in asymptomatic stages. Their prognosis is not different from those
      with symptomatic recurrence. Routine follow-up after gastrectomy can be
      abandoned.

PMID- 9574238
TI  - [Medical education in crisis].
AB  - BACKGROUND: The controversy about the value of current undergraduate medical
      education in Germany. PROBLEM: Are there empirical data about economic evaluation
      undertaken to investigate the value of medical education? METHOD: Case study.
      Literature review with MedLine. ENDPOINTS: Utility of the curriculum, indicated
      by (1) prevalence of vocational demands reflected in the curriculum content; (2)
      students' performance as MDs; (3) student's dissertation rate; (4) synthesis of
      basic sciences, clinical sciences and practical work; (5) mentoring provided by
      faculty; and (6) cost-benefit analyses. RESULTS: 1. Selection bias of clinical
      education: only 3% of the incidence of diseases are seen in university hospitals,
      the main educational experience in Germany. 2. No objective performance data
      available in Germany. 3.91% of the students wish wo write a dissertation, but
      only 38% of the graduates, by their third year, have attained that goal by
      receiving the title Dr. med. 4. Practical education in GP practice in the US and
      UK starts in the students' 1st year; in Germany, in the 4th year. 5. More
      mentoring is desired by 66% of the students. 6. No German cost-benefit analyses
      could be retrieved. CONCLUSION: We face a quantifiably severe crisis in medical
      education. An approach to quality management, of which economic evaluation is an
      integral part, would be suitable to improve teaching quality.

PMID- 9574239
TI  - [Changes in postgraduate education (health policy prerequisites, work schedule
      regulation)].
AB  - Postgraduate training is an integral part of becoming a doctor. Postgraduate
      training in Germany is learning by doing, while working as a doctor. Due to an
      extension of the in-patient sector and intensifying out-patient care as well as
      by new regulations for working time, resources for postgraduate training have
      obviously diminished. There is a clear disproportion between the demand for
      postgraduate-training posts and the corresponding supply. By flexibilisation of
      the regulations for postgraduate training and by complementing methods for
      training and learning, the downward movement of the capacities for postgraduate
      training will be taken care of.

PMID- 9574240
TI  - [Education, postgraduate and continuing education in surgery--data for quality
      control].
AB  - Despite intensive educational training during medical school, there is hardly any
      occupational group like physicians that tries to keep further education on a very
      high level. However, under the aspect of quality control, there is a need for
      different certificates. The education itself needs quality control; the laying
      down of rules as a rational basis is to advance, but facts that deal with quality
      control are not easy to find. The analysis of the committee of education of the
      Ruhr University Bochum must be considered as ideal; the results have to be
      transferred. Objective medical care results and patient satisfaction are
      influenced by many factors.

PMID- 9574241
TI  - [Value of training courses in minimally invasive surgery].
AB  - The actual situation regarding the education fur MIS requires the optimisation
      and standardisation of the training system. This paper presents the results of an
      inquiry about the evaluation of the course of operative laparoscopy. 80-90% of
      those interviewed made the comments "very good" and "good", with regard to the
      imparting of the theoretic foundation of the technique of endoscopic operations,
      for sufficient possibility of manual training and for the realistic setting of
      the animal organ model compared with the clinical operation. Because of our
      experience, we recommend attending such training courses before starting
      laparoscopic operations.

PMID- 9574242
TI  - [Role of the pulsatile organ perfusion surgical simulator in surgery education].
AB  - The operation simulator with pulsatile organ perfusion ("POP trainer") simulates
      the blood supply of organs or organ complexes and was developed for the training
      in both minimally invasive and conventional surgery. With the redesigned new POP
      trainer, even complex operations, such as colorectal and antireflux procedures
      can be practised. Due to perfect quality of simulation, simple handling and
      economic aspects, the POP trainer serves to intensify the training of surgeons,
      simultaneously decreasing the number of animal experiments.

PMID- 9574243
TI  - [Quality assurance in surgical education].
AB  - The authors determine the reliability, validity and usefulness of the "QuaSi"
      test, a test for the evaluation of surgical residents. METHODS: A test with
      multiple-choice (MC) answers was given to 47 surgeons, residents and interns of
      our surgery clinic. The reliability and validity of the tests were determined
      using statistical methods. RESULTS: The reliability of the test was very high.
      Performance varied significantly according to the level of training (postgraduate
      year). Surgeons performed best, then the senior residents; students and interns
      performed worst. CONCLUSION: The QuaSi-test is a highly reliable and valid
      examination that provides unique information about the performance of individual
      residents and the quality of postgraduate-training programs.

PMID- 9574244
TI  - [The status of postgraduate education in the area of surgery--results of a survey
      of the North-Rhine Physicians Group and the Bavarian Regional Physicians Group in
      cooperation with the German Society of Surgery].
AB  - Although in Germany most of the medical procedures have to be documented, there
      are almost no data available focusing on postgraduate training, especially in
      surgery. A retrospective analysis from 1 Jan to 31 Dec 1995 by the Chamber of
      Physicians in Nordrhein (AeK No) and the Bavarian (BLAEK) Chamber of Physicians
      revealed their surgical department's share of postgraduate trainees to be 59.2%
      and 63.6%, respectively. Operations per surgeon numbered approximately 220 p.a.
      (AeK No) and approximately 200 p.a. (BLAEK); mean hospital stay of patient
      equalled 10.3 d (AeK No) and 9.9 d (BLAEK). Especially in AeK No, there was an
      interesting follow-up when comparing 1985 with 1995; there was a decrease in the
      number of beds in the hospitals, a decrease of the length of patients' hospital
      stay, and an increase in the number of operations performed; there was an
      increasing number of surgeons per department, with a moderate increase of
      surgeons with postgraduate training completed.

PMID- 9574245
TI  - [Continuing medical education seminars of the professional society as preparation
      for specialist certification (surgery specialty and subspecialties)].
AB  - The Berufsverband der Deutschen Chirurgen (BDC) established the Academy for
      Surgical Education and Training and started in 1986 a structured educational
      program. It consists of an annual congress (Chirurgentag) and different seminars.
      In the meantime 15 seminars--nine in general surgery and six in surgical
      specialities such as traumatology and vascular, visceral, and thoracic surgery-
      are offered annually in 12 different locations in Germany. The basic seminars
      (since 1986) 5,264 and the specialised seminars (since 1992) have attracted 1,078
      participants. The evaluation of these educational efforts by the BDC in respect
      to the annual certifications by the official authorities (Landesarztekammer,
      Bundesarztekammer) demonstrates a high level of acceptance.

PMID- 9574246
TI  - [Bedside laparoscopy (BSL) for postoperative follow-up of mesenteric infarct and
      diffuse peritonitis].
AB  - Bedside laparoscopy (BSL) for postoperative follow-up in mesenterial infarction
      of the intensive care patient undergoing respiration treatment represents an
      important tool for avoiding second-look operations and/or for precisely securing
      the indication for a relaparotomy. Up until now, nine patients with mesenterial
      infarction have undergone a BSL, allowing five of then to avoid a second-look
      operation in this way. Of these nine patients, three died due to a diffuse
      peritonitis with anastomotic dehiscence, a pulmonary embolism, and a perforation
      of the stomach after PEG tube deplacement, respectively. Thus BSL represents a
      low-complication and simply performed method for postoperative follow-up,
      especially in mesenterial infarction, but also in cases of diffuse peritonitis.

PMID- 9574247
TI  - [Harmonizing European medical education, continuing and postgraduate education].
AB  - The harmonization of medical education, specialist training and continuing
      medical education (CME) in Europe progresses at different levels. University
      exchange programmes like ERASMUS and SOKRATES try to realize the European idea on
      the student and academic level. Specialist training is complicated by differences
      in responsibilities. The UEMS, based on various agreements, coordinates the
      harmonization process. Surgical training is represented by the European Board of
      Surgery (EBS). Its basic care and subspecialties have been described and European
      qualifications are being prepared. The content of education as well as log books,
      trainee qualification and training centers are regulated by position papers.
      Continued medical education is described in the Charter of Continued Medical
      Education of Specialists in which the content of training and requirements are
      defined.

PMID- 9574248
TI  - [European topic--multimodal therapy concept in gastrointestinal tumors-
      colorectal carcinoma].
AB  - Current knowledge of adjuvant treatment of colonic cancer demonstrates the
      influence of the quality of surgery per se on the oncological therapeutic
      outcome. The influence of the tumour stages is equivocal. Chemotherapy (perhaps
      vaccination treatment) exerts influence in Stage III and potentially in Stage IV.

PMID- 9574249
TI  - [Surgical and multimodal therapy of recurrent rectum carcinoma].
AB  - The following guidelines can be recommended for the treatment of recurrent rectal
      cancer: The therapeutical procedure depends on aetiology and shape of the
      recurrence. A surgical approach is worth striving for, if a R0-resection can be
      achieved. Multimodality therapy improves resectability and especially also the
      local recurrence free and overall survival time. Radiochemotherapy, possibly
      combined with hyperthermia or IORT are the most effective treatment strategies in
      combination with surgery.

PMID- 9574250
TI  - [Women physicians in surgery].

PMID- 9574251
TI  - [Women in surgery].
AB  - Women surgeons are also capable of their job as men surgeons. The part time job
      imports the balance between surgical career and family goals of a women
      neverseless respecting economics and efficiency in health care policy. To arrive
      equal conditions it seems to need a growth of the group of women surgeons and to
      get more role modells and mentors.

PMID- 9574252
TI  - [Women in surgery--the status at universities in North-Rhine-Westphalia].
AB  - As a part of the survey of "women in surgery" of the German Association of
      Surgeons data were collected of Nordrhein-Westfalen to characterize the
      participation of women in academic surgery: 1996 only 6 women held a faculty
      appointment, 4 were head physicians, 49 were residents and 14 interns.

PMID- 9574253
TI  - [Women physicians in a surgical university clinic 1980 to 1996].
AB  - From 1980 to 1996 214 male and 51 female physicians were employed at the
      Department of Surgery of the University Hospital of Lubeck (Germany). The
      percentage of female surgeons increased from 13% in 1980 to 20% in 1996.
      Nowerdays female surgeons more often succeed in becoming a specialist, a ward
      physician or senior physician. Female physicians often quit their job in surgery
      because of reasons in their family background (child care, change of place of
      their husband's job).

PMID- 9574254
TI  - [Women in surgery--equal surgeons].
AB  - In the specialty "surgery" women are underrepresented, especially in leading
      positions. The reason for that is not less motivation, less ability or less
      capacity of women, but the working conditions. For women in surgery working
      conditions are so unfavourable that only few women make their career in surgery.

PMID- 9574255
TI  - [Burnout syndrome in women in surgery].
AB  - During the past years the burnout syndrome has internationally gained importance
      especially within the medical professions. With the help of a questionnaire it
      was investigated at German clinics in how far the Burnout Syndrome occurs among
      female surgical interns, leading to the result that 68 percent of the poll
      participants have shown burnout. Reasons that lead to this burnout were among
      other things doing more than nine hours of overtime per week, the feeling of
      psychic and physical burdenings during operations as well as disappointed
      anticipation and unsuitable strategies to assimilate burdenings.

PMID- 9574256
TI  - [Physician-patient relations from the viewpoint of the surgeon].
AB  - The impressive caricatures from Dieter Hanitzsch drew attention to the changes in
      the state of health policy compared to earlier times. Accompanying this,
      different aspects which are relevant for the physician-patient relationship are
      depicted and the conclusion reached that the basic humanity of this relationship
      is always dependent on the initiative of the individual. For the reestablishment
      of medical credibility and medical professionality it is essential that the
      individual physician completes his task in an open, sincere, committed, and,
      above all, patient-oriented manner.

PMID- 9574257
TI  - [Work distribution and cooperation in surgery--horizontal and vertical decision
      and responsibility fields].
AB  - Horizontal delegation of labor in medicine means independent cooperation of
      medical specialties. Careful division and confidence in other physicians is very
      important. Vertical delegation of labor means cooperation between physicians in
      respect to hierarchical systems in the hospital or between physicians and nurses
      or medical technical staff members. Special problems have to be solved in the
      cooperation between the medical staff, on the other hand, and administration or
      nurses, on the other.

PMID- 9574258
TI  - [Cooperating with nursing care].
AB  - The highest standard, humanity in the care of patients, efficiency and budgetary
      responsibility are what is expected of the public health service. Outside
      pressure makes internal coordination more efficient and effective. Restructuring
      of personnel and non-personnel budgets within the limits of precision budgeting
      must be possible. In the interest of the overall goal, professional and
      individual interests must be put aside and subordinated. Coordinated routines
      within the occupational group and extended operational times of X-ray apparatus,
      the laboratory and so on must be possible. We should never forget that the
      patient must be the centre of attention in research, training and medical care.

PMID- 9574259
TI  - [Women in surgery].
AB  - There seem to be no gender-specific qualifications for surgery. Yet a traditional
      role model keeps the number of women involved small. The patriarchal character of
      surgery has hardly changed. Meanwhile, changes in social organisation, planning
      of life and division of labour inside the family have opened up surgery for women
      to a certain degree in recent decades.

PMID- 9574260
TI  - [Experiences and career of the surgeon].

PMID- 9574261
TI  - [Managing position of the surgery executive].
AB  - Recent legislation on health service has once again made the head of the
      department of surgery aware of his managing responsibilities. Cost saving will be
      possible in the areas of laboratory and high-tech diagnoses, surgery materials,
      storage of supplies, and administration of drugs. Since 70% of hospital costs are
      personnel costs, a substantial reduction in the hospital budget can only be
      obtained by reducing staff. In planning for the long term, we will be obliged to
      discuss "total quality management", which demands continuous improvement of the
      quality of our management and our patient treatment.

PMID- 9574262
TI  - [Performance in the tension field of rationalization and rationing].

PMID- 9574263
TI  - [The surgeon and his environment--surgery and the law].

PMID- 9574264
TI  - [Effects of social change on surgery].
AB  - The main social changes that have influenced medicine and surgery since the
      Second World War are growing criticism directed against science and technology,
      the understanding of the limits of economic growth, the institution of a system
      of social security for all, the loss of faith in the omnipotence of science and
      technology following numerous serious technical accidents and, last but not
      least, the invasion of economic ideas into the domain of medical thinking.

PMID- 9574265
TI  - [Performance and cost transparency as quality assurance measures].
AB  - The use of a Hospital Information System--Network Configuration, Information-
      Storage and Retrieval, Medical-Administration and -Documentation--lead in the
      Department of Surgery to positive effects concerning transparency and
      consciousness of costs and allowed an accurate budget planing and controlling of
      proceeds.

PMID- 9574266
TI  - [Unnecessary admission from the surgical social medicine viewpoint].
AB  - Wrongfully inpatient admission means unnecessary treatment of patients with the
      means of a hospital. In a study of the Medical Service (MDK) in the German state
      of Hessen 58% of 954 inpatients were considered wrongfully admitted. 199 patients
      were treated surgically, the wrongful admission rate of 63% is caused by an
      unnecessary duration of pre- and postoperative treatment time as well as by
      organizational deficits.

PMID- 9574267
TI  - [Verifying routine preoperative diagnosis between private practice and the
      surgical university clinic].
AB  - In an attempt to shorten the preoperative in-patient period and to avoid
      unnecessary investigations, a cooperative patient management model was
      established for a number of surgical operations at the University Department of
      Surgery, Anaesthesiology and their referring Specialist and General
      Practitioners. The latter were requested to carry out the previously defined
      preoperative routine investigations, which allowed for a marked reduction in
      hospital diagnostics. Ambulatory preoperative patient management and a new
      admission routine resulted in a 57% decrease of the average preoperative in
      patient stay for the observed procedures.

PMID- 9574268
TI  - [Are diagnostic codes in accordance with the SGB V regulation and classification
      of case fees and special charges a suitable instrument for controlling costs in
      surgery?].
AB  - The German health care system lacks transparency of efficiency and costs. Fixed
      compensations for common diagnoses and treatments were established to lower
      spending and to get better statistics of diagnoses and treatments. It could be
      demonstrated that the expenses are too high while the benefit is too small.

PMID- 9574269
TI  - [Automated data processing of special reimbursements and case fees in general
      surgery].
AB  - Based on the algorithm of defined combinations between diagnosis and surgical
      procedures due to the Gesundheitsstrukturgesetz an automatical detection of
      reimbursement with an electronic hospital information system is presented.

PMID- 9574270
TI  - [Problems in calculating and recalculating case fees and special reimbursements
      exemplified by a general surgery clinic].
AB  - A calculation of costs for the not perforated appendicitis was performed. The
      main costs are the nursing costs on ward. As one of the consequences we have to
      prove the intensity of nursing and the resulting classification to reduce the
      depending more costs of 200 DM.

PMID- 9574271
TI  - [Measures for increasing efficiency in surgical departments of the Hamburg LKB
      with special reference to regional hospital comparisons].
AB  - A comparative study was performed using the medical records of 40,000 inpatients
      undergoing treatment in surgical units of 10 hospitals. The results show that the
      number of patients, the kind of diseases or injuries and the time required for
      their treatment do not correlate with the classification of the hospital or the
      degree of specialization of the surgical unit. Therefore, for every group of
      diseases (expressed as ICD number), standards (mean, median, benchmark) can be
      defined which should be followed in order to reduce the time of treatment and to
      improve the efficiency of the unit.

PMID- 9574272
TI  - [Center management: chance or risk?].

PMID- 9574273
TI  - [Electronic data processing in ward management--possibilities for rationalization
      and cost control].
AB  - Electronic data processing in ward management increases cost and time efficiency.
      Nurses and doctors will have more time to concentrate their genuine rather than
      administrative duties. Therefore the presented model has gained high acceptance.

PMID- 9574274
TI  - [Risk management to control increased and more costly malpractice suits].
AB  - Considerable increase of premium for risk-insurance demands now risk management
      (RM) in German hospitals. RM is more than quality management and has other goals.
      The method we are using to analyse the risk in hospitals is given in detail. By
      this way we cover the main groups of potential personal damage of patients and
      reasons and fundamentals to sue the hospital. There is no total quality
      management (TQM) in hospitals without RM in the medical field. RM can be
      successful only with the awareness of medical and nursing staff for risks and
      liability claims. In our experience there is a lot of potential damages and
      sources of liability demands even in hospitals which seem to be well managed.

PMID- 9574275
TI  - [The physician as manager--medical department coordination as a reaction to
      changed responsibilities].
AB  - As a reaction to the changing situation in the public health service, we have
      changed a senior house officer post into a job for medical management out off our
      own motivation. In the sense of job sharing, the department has now got an expert
      with medical competence for the new business. He is the connecting link between
      the department and the administration of the hospital.

PMID- 9574276
TI  - [Optimal and computer-assisted hospital cost control by the surgeon].
AB  - Considering the legal conditions there is no question that with the health reform
      law (GSG) changes in hospital infrastructure have to be made by the surgeon and
      the administration cojointly. From our experience an efficient budget control
      needs a complete and correct data recording--employing an efficient software--as
      well as strict medical control of profits along with continuous communication
      between the surgeons themselves and with the administration.

PMID- 9574278
TI  - [Profile and structure of future-oriented visceral surgery in a non-university
      environment].
AB  - A nationwide limitation of the total health care budget requires the shutdown of
      certain departments or complete hospitals in order to increase the budget for the
      surviving hospitals. This development involves surgical departments as well,
      which have to be re-designed for an economic future.

PMID- 9574277
TI  - [Rationalizing the organization and structure of a trauma surgery clinic based on
      rationing of personal and financial resources--analysis, simulation and
      conversion using modern data processing techniques].
AB  - With a system of modeling, simulation, animation of information, communication in
      medicine (mosaic-m) the structures of organisation and information in a level 1
      trauma center were analysed and animated as a virtual environment on screen in a
      first step. One result: in existing paper orientated documentation 50% of
      documentation was redundant. In a second step the requirements of the future
      information system were described systematically, user- and organisation
      oriented. All components (hard- and software) were simulated an screen that the
      user could work virtually in the future working place. With mosaic-m the user is
      fully integrated in analysing and developing a new information system in the
      clinic.

PMID- 9574279
TI  - [Cost data of standard surgical interventions].
AB  - Personnel and nonpersonnel costs of seven surgical standard procedures were
      calculated related to the patient. Nonpersonnel costs were up to 57% below to the
      figures of the Ministry of Health. Personnel costs ranged from 3.2% to 30% less.
      The result of a patient related calculation will lead to more efficiency by
      changing a faulty organisation, the management of the personnel, the indication
      for surgical procedures and the surgical technique.

PMID- 9574281
TI  - [Development of treatment guidelines and procedure guidelines within the scope of
      developing case fees and a modular quality management system (MQM)].
AB  - Since 1991 Diagnostic Related Groups (DRGs) are systematically developed for
      standardized operation procedures. They are included in a Quality Management
      System of the DIN EN ISO 9001 ff. norm and are part of the process system. In
      additional the internal and external evaluation of quality completes a Modular
      Quality Management System (MQM). These procedures meet the requirements for a
      Total Quality Management (TQM).

PMID- 9574280
TI  - [Use of the ICPM surgical key: initial experiences in routine clinical
      documentation and reimbursement calculation].
AB  - The German version of the International Classification of Procedures in Medicine
      (ICPM) [3] is used in the Department of General Surgery of Gottingen University
      since 1995. There is full compatibility with the official catalogue of operations
      (OPS-301) [4] for administrative purpose combined with a more sophisticated
      medical classification. The ICPM may become a reference system for scientific
      evaluations of surgical treatment [1].

PMID- 9574282
TI  - [The medical pathway system: a two-dimensional matrix for converting guidelines
      to routine practice].

PMID- 9574283
TI  - [Quality assurance of GSG data, problems and possible solutions].
AB  - Acquisition and controlling of data by our developed knowledge based system
      extensively substitute human manual controlling of basic data. It is absolutely
      necessary because it is the only way to prevent expected high error rates and
      accomplish the lots of data. You have to do it before data transferring to health
      insurance.

PMID- 9574284
TI  - [Evaluation and internal quality assurance in general and abdominal surgery].
AB  - The measuring of perioperative risk, the finding of intraoperative influences and
      the objective rating of quality of treatment were achieved by our program of
      quality assurance. With our system it is possible to measure differences between
      several surgeons and also differences in comparison to national and international
      results. Through optimised therapy the program can lead to an improvement of
      quality.

PMID- 9574285
TI  - [Quality and cost reduction: corresponding goals of strategic reorientation of
      hospitals].
AB  - Industrial quality management has taught that costs are not induced by high
      quality but by non-quality. The medical literature suggests that this might also
      hold true in medicine and furthermore reveals factors directed concurrently at
      lowering costs and at increasing quality: These include personal and
      institutional case load, implementation of guide lines supported by information
      technology as well as innovative organizational structures and principles of
      reimbursement.

PMID- 9574286
TI  - [Itinerary through 125 years of German Surgical Congresses].
AB  - The German Society of Surgery was founded in 1872 with 127 members. Now there are
      more than 5000. The first congress was attended by 81 members. In those days, a
      lively discussion was possible. Meanwhile, many subspecialties have developed
      from general surgery, which articulate themselves in parallel sessions. For these
      reasons, a discussion in the plenary does not exist anymore. The conventions
      predominantly communicate results. No original innovations were recognized
      immediately. This is evident from examples. Today the industrial exhibition is an
      important factor for the progress which is linked to these congresses.

PMID- 9574287
TI  - [Prospects].
AB  - With the warning that the future is always different than you imagine, the
      following considerations were discussed: currents issues; institutionalisation of
      commission of programms; standing order for the congress; publication of
      proceedings; increased engagement in the scientific forum and modern surgery;
      more interdisciplinary participation and involving surgical practitioners in the
      congress; a close cooperation with the German Society of the Profession;
      supporting and protecting innovation; cooperation with the Society of Public
      Health; regular public relations work; overcoming political naivety; discussions
      on "one-week surgery" with the participation of related groups; traditional
      surgical societies; and upholding the sovereignty and necessity of a larger unity
      of surgery.

PMID- 9574288
TI  - [How does the surgeon deal with forensic risks?].

PMID- 9574289
TI  - [Responsible conversion to new technology in surgical practice].
AB  - The continuing rapid increase in medical knowledge with its more complex
      technology together with the experiences we have made during the introduction of
      minimal invasive surgery suggest that the traditional methods of surgical
      teaching and learning do not suffice. The responsible application of new surgical
      technologies must engage a step by step introduction process, including
      standardized training courses at institutions with adequate training facilities.
      Uncontrolled ubiquitous spread of new methods without sufficient evaluation and
      quality control is dangerous and should not be allowed to repeat itself.

PMID- 9574291
TI  - Plenary session. Current ethics in surgery. Introduction.

PMID- 9574290
TI  - [Quality and innovation management in surgery for the patient's benefit].
AB  - While the objective of management of innovations is to move the achievable
      quality in the direction of maximum quality, the purpose of quality management is
      to achieve the achievable quality everywhere. Other than in pharmaceutical and
      medicinal products and in out-patient care, there is no systematic technology
      assessment for hospital care in Germany. Before broadly implementing innovations
      in health care, they have to be embedded in good clinical practice guidelines to
      assure their appropriate indication and performance. Since health insurance funds
      are the greatest profiteers, they should fill the financial gap for the research
      of transferring innovations into daily medical practice.

PMID- 9574293
TI  - [The limits of medical responsibility in surgery].

PMID- 9574292
TI  - Medical ethics in today's society.

PMID- 9574294
TI  - [Functional disorders of the rectum and pelvic floor--surgical diagnosis].
AB  - Pelvic-floor disorders present themselves as isolated entities or, often, in
      combination with other ano-rectal diseases. In each case, the basis for
      individual therapy has to be a precise diagnosis. For differentiation of pelvic
      floor disorders, we use a step by step diagnostic cascade: the first step is a
      basic proctological evaluation, including history, scoring, inspection,
      palpation, proctorectoscopy and anorectal manometry. Secondary special
      diagnostics, such as endosonography, neurological examination, transit-time
      studies and defecography are also used. In special individual problems, CT scan,
      MRI, urological or gynecological examination complete the diagnostic route,
      resulting in the definite coloproctological therapy.

PMID- 9574295
TI  - [Neurophysiologic diagnosis in proctology].
AB  - Functional diagnostic exploration in proctology is ever-expanding and becoming
      more differentiating. Neurophysiologic examinations can take over an essential
      share. They have in part already been introduced into routine diagnostic workup.
      Both afference and efference, as well as the muscular system can be investigated
      in functional neurologic disorders of the pelvic floor. The electromyogram using
      concentric needle electrodes constitutes the most significant tool. It provides
      us with a better verification of the neurogenic lesion, and enables us to
      discriminate between acute and chronic and comment on severity and prognosis. The
      diagnostic program is additionally supplemented by motor and sensory evoked
      potentials, electroneurography of the pudendal nerve, and measurements of
      vegetative nerve paths.

PMID- 9574296
TI  - [Laparoscopic therapy of functional disorders of the rectum and pelvic floor].
AB  - Within 4.5 years, 72 laparoscopic rectopexies were performed. The indications
      included rectal prolapse, morphologic outlet-constipation and a combination of
      both. Using a modified suture rectopexy (according to Sudeck), without taking any
      foreign material we resected the sigmoid in 39 patients. In four cases, a
      resection of the sigmoid colon was carried out. Conversion rate was 2% and
      complications that needed reoperation occurred in 9%. No patient died; laparotomy
      rate was only 4%. In the mean follow up period of 24.1 months (max. 50 months),
      no recurrent prolapse occurred. Incontinence was abolished or improved in 64% and
      outlet-constipation was improved in 85%. Laparoscopic rectopexy with or without
      sigmoid resection seems to be of benefit for the patient: quicker convalescence;
      less pain; small scars; no recurrence; and improvement of constipation and
      incontinence.

PMID- 9574297
TI  - [Open surgical therapy of functional disorders of the rectum and pelvic floor].
AB  - An overview is given of common transabdominal procedures for functional disorders
      of the rectum and pelvic floor which are caused by degenerative morphological
      changes, and termed pelvic floor insufficiency. Only the transabdominal approach
      permits a comprehensive and pathophysiological repair of changes associated with
      the disorder. Own results and a review of the literature confirm a superior
      functional outcome and low recurrence rates with a combined procedure consisting
      of rectopexy, colonic resection and pelvic floor repair.

PMID- 9574298
TI  - [Therapy: perineal operation].
AB  - In most cases, the pelvic floor insufficiency is the result of combined traumas,
      degeneration and functional disorders of the rectum, pelvic floor and the anal
      canal with a great variety of terms and, therefore, unclear indication of special
      operative procedures. The internal or complete rectal prolapse may be removed by
      the Delorme's procedure, without causing damage to the pudendal nerves. The
      increase in defaecatory control is significant and the complication rate is
      tolerable. The best outcome will be achieved by suturing of the traumatic
      dissected sphincter muscles, without neurogenic injury during vaginal delivery in
      about 80 to 90 percent. Parks' post-anal repair, in addition to the other
      procedures, may increase the resistance to the egress of rectal contents.

PMID- 9574299
TI  - [Functional disorders of the rectum and pelvic floor. Ambulatory/conservative
      therapy].
AB  - Early diagnosed functional disorders of the ano-rectum or pelvic floor can be
      treated in the office by conservative treatment or out-patient surgery. The
      normal anatomy of the anal canal must be restituted by reducing enlarged
      haemorrhoids, removing a prolapse of the anterior rectal wall with rubber-band
      ligation, excision of chronic fissures and prolapsing tumours. The basic therapy
      then consists of normalisation of bowel habits and stool consistency. An anal
      stenosis must be dilated. Training of the sphincter, gymnastics of the pelvic
      floor, electrostimulation and biofeedback are the therapy for the sphincter and
      pelvic floor insufficiency.

PMID- 9574300
TI  - [Biofeedback].
AB  - The overall success rate of biofeedback in ano-rectal incontinence and chronic
      constipation is reported to be 50-92% and 35-90%, respectively. In patients with
      neurogenic incontinence, the results are poor. Biofeedback, in case of outlet
      obstruction, seems only to be useful if there is paradoxical contraction of the
      external anal sphincter and/or the puborectalis muscle during straining
      (anismus). Further investigations to select patients who would profit from this
      therapy are, therefore, necessary.

PMID- 9574301
TI  - [Laparoscopic fundoplication--prevention of complications].
AB  - False indications, inadequate procedures and incorrect technique cause
      complications after laparoscopic antireflux procedures. Indication for operative
      treatment are esophagitis grade III and IV. Requirement of life-long treatment as
      well as persisting esophagitis after conservative treatment are indications in
      patients with esophagitis grade I and II. Preoperative evaluation includes
      endoscopy with biopsy, 24-h pH measurement and manometry. Therapy of choice is
      360 degrees Nissen fundoplication analogue to the open procedure. In case of
      impaired esophageal contractility, a Toupet fundoplication is performed.
      Essential steps of the operative technique are prescribed with respect to
      potential peri- and postoperative complications. With crucial indication, careful
      preoperative evaluation and subtle technique, a fundoplication performed by an
      laparoscopic experienced surgeon is safe and efficient.

PMID- 9574302
TI  - [Prevention and therapy of complications in laparoscopic appendectomy].
AB  - It has been verified that laparoscopic appendectomy increases safety. The
      indications for laparoscopic appendectomy depend on the surgeon's confidence in
      diagnosis, his skills and the stage of appendicitis. The complications could be
      prevented by placement of open trocars and (dividing the mesoappendix and
      appendix with sutures, clips or staples. Electrosurgery should never be used.
      Bipolar electrosurgery should be limited to 20 Watt power for 5 s. The appendix
      is removed either though a trocar or in a specimen bag.

PMID- 9574303
TI  - [Laparoscopic hernia repair: prevention and therapy of complications].
AB  - Following the surgical steps in laparoscopic (transperitoneal) hernia repair, the
      corresponding groups of complications relate to: (1) laparoscopy; (2) the
      trocars; (3) the dissection of the inguinal region; (4) the hernia sac
      dissection; (5) the mesh placement; (6) the peritoneal closure. Inadequate
      surgical technique can lead to injuries of the intestine, urinary bladder and
      blood vessels; peri- and postoperative bleeding and hematoma; severing of
      testicular blood vessels, with consecutive testicular atrophy; and nerve lesions
      when fixing the mesh with clips and intestinal obstruction subsequent to
      insufficient peritoneal closure. With an adequate surgical technique,
      complication rate is very low. Preconditions for this are: strict compliance with
      the safety tests, when establishing the pneumoperitoneum; application of blunt
      conical trocars; precise knowledge of the anatomy; gentle dissection in the
      avascular tissue layers; subtle hemostasis; absolutely no diffuse
      electrocoagulation or placement of any clips below or up to 1 cm above the
      ileopubic tract; and safe peritoneal closure by suture under reduced
      intraabdominal pressure.

PMID- 9574304
TI  - [Infection without infection focus--clinical relevance of bacterial
      translocation].
AB  - The passage of bacteria, fungi, and bacterial products through the gut wall,
      which is called microbial translocation, is an experimentally well-defined
      process occurring during burn injury, multiple trauma, and septic diseases. The
      translocation of viable bacteria could be demonstrated in humans as a sporadic
      event, but despite accumulating evidence the clinical relevance remains to be
      elucidated. The same fact is true for the translocation of bacterial products
      such as endotoxin. Although a large body of evidence supports the hypothesis that
      endotoxin of gut origin may play a pathophysiologically important role, general
      acceptance is still lacking because some clinical studies provide disappointing
      results due to unrecognized methodological problems.

PMID- 9574305
TI  - [Abdominal infect--what does radiologic diagnosis contribute? Required and
      superfluous tests].
AB  - Multiple radiological techniques can be employed to search for the source of
      abdominal sepsis. Plain abdominal film can give important direct or indirect
      information about the origin of sepsis. Computer tomography plays the most
      important role. Abscesses with their typical signs (gas within encapsuled
      extraluminal fluid, enhancement of membrane), as well as embolism and thrombosis,
      can be reliably detected as sources of sepsis. Magnet resonance imaging is an
      alternative for patients who would otherwise be regularly exposed to X-rays (e.g.
      in Crohn's disease). Dependent on the clinical setting studies of the
      gastrointestinal tract with water-soluble contrast media are indicated (e.g. for
      detection of fistulas or insufficiency of an anastomosis). Angiography and
      scintigraphic studies are not helpful in the search for the source of abdominal
      sepsis.

PMID- 9574306
TI  - [Aspects of calculated and controlled antibiotic therapy].
AB  - Strategies for selection of antimicrobial agents may include estimation of the
      most appropriate agent (empirical therapy), or planned escalation or de
      escalation therapy. Severe and life-threatening infections such as peritonitis
      have a particularly poor prognosis if the initial therapy fails. Hence, in these
      cases a de-escalation therapy employing broad spectrum agents with proven high
      efficacy should be employed, and selection pressure arguments and cost
      considerations should be immaterial. After 48 to 72 hours, this initial therapy
      should be reconsidered (de-escalated to less powerful agents), especially in
      light of the microbiological test results.

PMID- 9574307
TI  - [Interventional therapy of intra-abdominal abscess: outcome and limits].
AB  - The postoperative course following digestive surgical procedures was
      prospectively analysed in 2985 patients between 6/92 and 12/96. A CT-guided
      percutaneous drainage of intraabdominal abscesses was performed in 144 patients
      (4.8%). In 123 patients (85.4%) percutaneous abscess drainage (PAD) was
      successful, additional surgery was not required. Twenty-one patients (14.6%)
      underwent additional surgery. Reasons for drainage failure were abscesses caused
      by internal fistulas (8 patients), pancreas involvement of the abscesses (5
      patients), infected clots impossible to drain (3 patients), multiple abscesses (3
      patients) and persistent abscess formation despite drainage (2 patients).
      Puncture-related complications were seen in 8 patients (5.5%). Puncture-related
      mortality was 0.7%.

PMID- 9574308
TI  - [Surgical therapy of diffuse peritonitis--staged lavage].
AB  - Better understanding of pathophysiology and improved techniques of intensive
      medical care resulted in new concepts of aggressive treatment for diffuse
      peritonitis. All consider the importance of surgical removal of the infectious
      focus but also the necessity of further treatment following first surgical
      intervention in cases of severe peritonitis. No randomised clinical study yet
      exists. Indication and application of selected therapeutic technique result from
      clinical criteria and experience. Presently used concepts are described and
      evaluated from a clinical viewpoint.

PMID- 9574309
TI  - [A time and priority-oriented algorithm].
AB  - Algorithms represent a graphical display of decision-making by giving clearly
      defined and formalized guidelines. The systematic order of decisions and
      consequent actions is guided by medical priority and regulates the time frame and
      sequence of each single step in a logical manner. With the help of clinical
      algorithms highly complex processes such as the management of the severely
      injured patient can be translated into a clearly structured, logical pathway.
      They delineate a consistent and valid guideline but require aberrations in proven
      exceptions. The use of algorithms allows a systematic search for errors in the
      process of quality management. In emergency situations they suggest a structured
      way of problem-solving to the less experienced user. Algorithms are useful
      instruments in teaching medical decision-making.

PMID- 9574311
TI  - [Responsibilities of the emergency service of the federal army in foreign
      interventions].
AB  - The security environment of our country has undergone a fundamental change since
      the end of the East-West confrontation. This has led to an extension of the
      Federal Armed Forces' mission to include, apart from military national defence,
      participation in multinational and supranational missions abroad. The Medical
      Service must adapt to this new mission. Emphasis is no longer placed on medicine
      with limited means, but rather on field medical support, whose procedures and
      measures guarantee a level of quality in missions abroad which is equal to the
      standard of medical care in Germany. Surgery in field operations comprises the
      entire spectrum of surgical medicine and makes it necessary to have field
      surgeons who have received follow-on training, particularly in traumatology.
      Preclinical care is conducted in rescue stations and rescue centres which fall
      under the responsibility of the Services, while immediate clinical care is
      provided in the hospitals and station hospitals of the central medical service.

PMID- 9574310
TI  - [Shock room management in severe craniocerebral trauma].
AB  - Early clinical management of severe head injury should take place in an emergency
      resuscitation room and be conducted according to the guidelines of the treatment
      of severely injured patients with attention given to time. The first phase (with
      a maximum duration of 30 min) comprises physical examination, stabilisation of
      vital functions and basic technical diagnostics. With pulmonary and circulatory
      functions stabilized, the second phase begins with a craniol computed tomography
      examination followed by adequate therapeutic measures, including, if necessary,
      the CT-controlled implantation of an intracranial pressure catheter.

PMID- 9574312
TI  - [Deployment surgery from the viewpoint of the German Red Cross].
AB  - The German military coinages "deployment medicine" and "deployment surgery" are
      unusual within the Red Cross Germany (DRK). For its (surgical) deployments, the
      DRK complies exclusively with the principles of the International Red Cross and
      Red Crescent Movement. The mobile surgical unit of the DRK's rapid module system
      is an intentionally "low-tech" medical/surgical unit that also does without any
      dispensable medical conveniences. For its purposes and objectives it is optimally
      equipped, and enables the DRK to provide prompt and flexible regionally adjusted
      relief that is compatible with the Red Cross worldwide.

PMID- 9574313
TI  - [Coordination of surgical relief concepts in the international community].
AB  - Concerned by the increasing number and extent of disasters, the international
      community declared the period from 1990-2000 an international decade for natural
      disaster reduction (IDNDR). The "United Nations Disaster Relief Organisation"
      (UNDRO) was restructured into the "Department of Humanitarian Affairs" (DHA) to
      study ways and means of improving the co-ordination of international relief
      operations at the site of a disaster. This included the establishment of the
      "United Nations Disaster Assessment and Co-ordination Stand-by Team" (UNDAC) and
      the "On-site Operations Co-ordination Centre" (OSOCC) concept. Surgical relief
      teams had to implement new concepts regarding mission indication, guidelines,
      ethical code of conduct and measures of improved prevention, rehabilitation,
      reconstruction and sustainable development.

PMID- 9574314
TI  - [Previous deployment of military service--an efficacy analysis].
AB  - Until the reunification of Germany, the medical services had to provide for the
      medical treatment of soldiers during peacetime and initial surgical care for the
      wounded in case of war. Since reunification a new quality of medical treatment
      was required for the support and treatment of German soldiers abroad. This
      resulted in the need to provide treatment similar to the civil standard in
      Germany. (Guidelines of the Surgeon General of the German Army). All personnel
      material and facilities follow these guidelines. An analysis of efficiency and
      efficacy prove this claim demonstrate the justification for these guidelines
      under the changed conditions new prevailing.

PMID- 9574315
TI  - [Experiences as a surgeon in a mobile hospital of the German Red Cross--German
      Referral Hospital/Benaco (Tanzania)].
AB  - The German Red Cross Society participated in the international aid activities for
      the refugees of Ruanda. Among other duties the German Red Cross became
      responsible for the medical care of the refugee camp population of Benaco,
      Tanzania. From 1994 until 1997 the German Red Cross used its so-called Module
      Hospital. This is a transportable hospital, which can be installed within a few
      days. The technical facilities of this hospital are well adapted to the
      conditions of medical work in developing countries. The authors, who are
      surgeons, report about their experiences in this sort of emergency surgery.

PMID- 9574316
TI  - [Treatment of burns in foreign military posts].
AB  - Even under the conditions of operations out-of-area severely burned soldiers have
      to receive a treatment that is in its outcome equivalent to the medical standard
      in Germany. On the bases of equipment and personnel the adequately trained
      members of the medical services of the German Forces are able to meet this high
      standard. Besides the generally accepted and standardised procedures, carbon
      wound dressings, due to their tolerance and easy handling, should be used for the
      topical treatment of burns under out-of-area conditions ("Koblenzer Modell").

PMID- 9574317
TI  - [Femur osteosynthesis in the polytrauma patient--considerations for reasonable
      surgery time frame from the viewpoint of military service medical treatment].
AB  - OBJECT: What are the concepts of secondary osteosynthesis in polytrauma patients?
      What are indicators underlying these concepts? Are there consequences for
      Military Medicine? RESULTS: Conservative stabilization techniques are unsuitable.
      The intramedullary nail is considered to be large-scaled and technically
      demanding. It leads to additional stress for the patient (second hit). The
      following parameters are not suitable: General status, soft-tissue condition,
      lung fluid, thrombocytes, PNM elastase, cathepsine, lactate, CRP, neopterin, AT
      III, t-PA-inhibitor, PFI-index, bilirubin. CONCLUSIONS: An objective parameter
      for the choice of the proper timing of definitive fracture treatment does not
      exist. In the literature, only few parameters are enumerated. Inconsistent
      recommendations are hardly discussed. Therefore, from the viewpoint of Military
      Medicine, we recommend external fixation for primary stabilization. Finally, the
      systemic inflammatory response has eased off after 5-7 days. Then the definitive
      operative procedure--intramedullary nailing--should be planned.

PMID- 9574318
TI  - [Possibilities of telemedicine within the scope of military medical interventions
      at foreign posts].
AB  - Telemedicine is the investigation, monitoring and management of patients and
      staff using systems which allow ready access to expert advice and patient
      information, no matter where the patient or the information is located.
      Telemedicine and teleconsulting have the potential to improve out-of-area
      military medical care by increasing patient/provider access to specialized
      medical facilities, services and talent. Similarly, telemedicine can help reduce
      medical costs by reducing the cost of traveling to and from remotely located
      medical facilities and services. The Army medical telemedicine effort allows
      electronic transmission of medical information from remote sites to a designated
      hub where the transmitted information is available for electronic diagnosis and
      consultation by health care specialists.

PMID- 9574319
TI  - [Military surgery: an additional "emphasis" in surgery?].
AB  - The German armed forces and the civilian help organisations need competent and
      well-trained general surgeons to deal with the specific problems of war or other
      casualties. This is in contrast to the modern training modalities which are going
      into extreme specialisation. The term "mission surgery" comprises a very specific
      training for surgeons under the adverse conditions of war or catastrophe. It is
      not intended to create a new subset within the different surgical specialties,
      but to elucidate the skills which are needed for mission surgery. To achieve
      these objectives, the young surgeon should undergo basic training with a broad
      clinical spectrum. It is recommended that the requirements of trauma or
      orthopedic surgery should be fulfilled.

PMID- 9574320
TI  - [Perioperative antibiotic prophylaxis from the microbiological viewpoint].
AB  - The practice of using antibiotic prophylaxis before surgery has evolved greatly
      in the past 20 years and is regarded as the third cornerstone in the prevention
      of postoperative wound infections. In contrast to asepsis and antisepsis, which
      have been standard techniques for almost a century, perioperative antibiotic
      prophylaxis is all too frequently administered in a suboptimal fashion. During
      the last few years, improvements in the timing of initial administration, the
      appropriate choice of antibiotic agents in each clinical setting, and the
      limitation of the duration of administration have defined more clearly the value
      of this technique in reducing postoperative wound infections. Implementation of
      these guidelines must be regarded as major issues in improving the quality of
      care in surgery.

PMID- 9574321
TI  - [Perioperative antibiotic prophylaxis in visceral surgery--pro and contra].
AB  - Perioperative antibiotic prophylaxis aims at reducing the enormous cost of
      hospital-acquired infections. Primary indications for antibiotic prophylaxis are
      wounds of the clean-contaminated and contaminated category. Use of antibiotic
      prophylaxis in clean surgery is still very controversial. To be effective, the
      antibiotic must be given in the period immediately before incision. A single-dose
      application is at least as effective as a multiple-dose regimen. Second
      generation cephalosporins are still the main stay of antibiotic prophylaxis. In
      colorectal surgery they should be combined with, e.g., Metronidazol.

PMID- 9574322
TI  - [Comprehensive range of services for general hospitals in the area of organ
      donation nearly doubles the number of donors in 2 years with a simultaneously
      economical process].
AB  - To overcome the donor shortage, any potential donor resource must be detected. By
      establishing a professional service for peripheral hospitals, the numbers of
      donors available in small hospitals could be nearly doubled: 85% of all donors in
      our region come from nonuniversity hospitals. By using total quality management
      techniques, the time requirements for organ donation after confirmation of brain
      death and given consent could be reduced to 6 h.

PMID- 9574323
TI  - [Kidney transplantation from living donors].
AB  - Because of the severe shortage of cadaver organs, the transplantation of living
      donated organs from related and also from unrelated donors has been suggested;
      graft survival is similar or better than with cadaver kidneys. Therefore, kidneys
      from living donors are a large and valuable source for transplantation which help
      increase the pool of organs and thus decrease the time spent waiting for organ
      transplantation.

PMID- 9574324
TI  - [Does preoperative corticoid administration reduce the incidence of acute
      rejections after kidney transplantation?].
AB  - Primary immunosuppressive therapy in renal transplantation is mediated by
      glucocorticosteroids with a delay of several hours. Consequence of the common
      practice of using first dose of steroids intraoperatively is a first contact of
      antigens with an unaltered immune system. In a prospective study on 111 renal
      transplant patients, we could show by the parameters of in vitro cytokine
      generation and acute rejection episodes that immunological responsiveness can be
      altered by early (5 h) preoperative use of glucocorticosteroids.

PMID- 9574325
TI  - [Extensive plasma exchange in treatment of acute vascular graft rejection of the
      kidney and pancreas].
AB  - Twenty-eight histologically proven severe acute vascular rejection episodes in
      renal grafts were reversed in 22/28 (78%) cases by extensive plasma exchange,
      which was well-tolerated by all but one patient. CMV infection was the most
      frequent complication. As 1-year survival of 93% (patient) and 71% (graft) is
      considered a good result in this severe immunological complication, the extensive
      plasma exchange can be recommended for the treatment of acute vascular rejection.

PMID- 9574326
TI  - [Long-term outcome of pancreas segment transplantation--obsolete technique or
      possible successful alternative?].
AB  - From January 1987 to August 1995, a total of 89 consecutive segmental pancreas
      transplants with bladder drainage were performed for end-stage diabetic
      nephropathy, the majority of them together with a kidney. One-year patient,
      pancreas, and kidney graft survival was 92%, 82%, and 87%, respectively.
      Rejection accounted for 64%, and thrombosis for 30% of total graft losses. While
      there was an increased risk of pancreas graft thrombosis, compared with duodenal
      pancreas transplantation, we experienced a lower incidence of urinary tract
      infections. In our series, segmental pancreas transplantation gives excellent
      long-term results.

PMID- 9574327
TI  - [Bladder drainage in pancreas transplantation--results of a consecutive series of
      100 transplantations].
AB  - Simultaneous pancreas/kidney transplantation has become a therapeutic approach
      for patients with renal failure resulting from type-I diabetes mellitus. However,
      the appropriate route for drainage of the exocrine secretions of the pancreatic
      gland remains unclear. While bladder drainage is the current state of the art, it
      is associated with a high frequency of urologic complications like urinary tract
      infections, hematuria, metabolic acidosis, and reflux pancreatitis.

PMID- 9574328
TI  - [Prevention of hepatitis B--analysis of cost-effectiveness after liver
      transplantation].
AB  - HBV recurrence, despite immunoprophylaxis which occurred in 67% of our patients,
      remains the main problem following liver transplantation for HBV infection.
      Pretransplant viral replication (HBV-DNA) and probably viral mutation may account
      to some degree for the failures involved in hyperimmunoglobulin prophylaxis. In
      order to improve the cost/benefit relationship, only HBV-DNA and HBeAG-negative
      patients should be selected or preoperatively seroconverted by nucleosides
      (famciclovir, lamivudine); post-operatively a variable HIG prophylaxis should be
      administered.

PMID- 9574329
TI  - [Preoperative routine chest x-ray: expensive and of little value].
AB  - In a retrospective analysis, we examined the findings of 3156 preoperative
      routine chest X-rays to define the indication of this cost-intensive examination.
      Pathological findings were seen only in 4% of all patients with no preexisting
      disease and in about 20% of patients with malignoma. Chest radiography is not
      routinely indicated in otherwise healthy patients, but should be performed if
      malignant disease is present.

PMID- 9574330
TI  - [Roentgen imaging in acute abdominal pain is dispensable].
AB  - Plain abdominal X-ray films are overused in patients with acute abdominal pain.
      Focusing on medical history and physical examination helps to reduce the number
      of plain films used and saves costs.

PMID- 9574331
TI  - [Postoperative complications in abdominal surgery--what do they cost?].
AB  - In this study of 154 patients with major abdominal cancer surgery, 41
      postoperative complications occurred and caused additional total costs of DM
      205.993,-, DM 5.024,- per case, respectively, where the special personnel costs
      were not accounted for. There was a significant difference between single and
      multiple complications as well as for early and late complication costs. Economic
      analyses are necessary to determine budgets of medical departments with extended
      and cost-intensive treatment, such as cancer surgery, to maintain optimal care
      for the patients.

PMID- 9574332
TI  - [Efficient ambulatory and post-discharge thromboprophylaxis with fully automated
      pens].
AB  - Efficient prophylaxis of deep vein thrombosis is very important during and after
      hospitalisation as well as for outpatients. In a prospective randomised trial, a
      new automatic pen for subcutaneous injections of low molecular heparin was
      studied with 489 injections in 51 patients. The automatic pen with a covered
      needle allows a safe and standardised subcutaneous administration of low
      molecular heparin with good patient comfort and at no additional costs.

PMID- 9574333
TI  - [What may surgical therapy of benign thyroid gland diseases cost? Extreme,
      moderate and ethically defensible calculations].
AB  - Since January 1996, Fallpauschalen (fee for case) and Sonderentgelte (fee for
      service) lead up to a new dictatorship of economy over surgeons affairs. A
      detailed economical analysis for the surgical treatment of benign diseases of the
      thyroid gland was made. Comparing the costs and our financial benefits, it is
      evident that there are no reserves for complications or longterm patients.

PMID- 9574334
TI  - [Gastrectomy with radical D2 lymph node excision--effective and economically
      standardized therapy of adenocarcinoma of the stomach].
AB  - In a retrospective single center study, the impact of radical D2-lymph adenectomy
      and splenectomy on operativ course, morbidity, mortality and long-term survival,
      in 243 patients who underwent radical surgical therapy for gastric cancer, was
      analyzed. D2-lymph node dissection during gastrectomy or gastric resection did
      not influence blood loss, artificial respiration time, ICU days or surgical
      morbidity, whereas splenectomy correlated with a higher hospital mortality,
      leakage and abscess rate. Due to routinely performed D2-lymphadenectomy long term
      survival rate (5 years) was 40.6% for all (in detail: 96% in stage IA; 68.5%/IB;
      61.2%/II; 35.8%/IIIA; 17.3%IIIB; and 2.6% in stage IV and 58.1% for curative
      resected patients.

PMID- 9574335
TI  - [Risk of gastrectomy for stomach carcinoma in relation to reconstruction
      methods].
AB  - Between 1982 and 1996 we performed 452 total gastrectomies due to gastric cancer.
      108 patients underwent a pouch reconstruction called Ulm pouch with preservation
      of the duodenal passage. In 251 patients, the reconstruction was made according
      to Hunt-Lawrence-Rodino and in 93 patients, a Roux-en-Y reconstruction without
      pouch was performed. In the Ulm pouch group, the rate of anastomotic leakage as
      well as the 30-day mortality was 0.8% and its relative risk was 2.6 times lower
      than in the other reconstruction groups (n = 452) and therefore, this type of
      reconstruction can be recommended for all curatively resected patients also with
      regard to morbidity and mortality.

PMID- 9574336
TI  - [Prognostic factors in gallbladder carcinoma as a decision aid for reoperation].
AB  - In a retrospective study of patients with gallbladder carcinoma, predictive
      factors for survival were evaluated. TNM stage, according to the UICC and
      complete tumor resection, turned out to be the strongest values in multivariate
      analysis. So it is important to make an early correct diagnosis and to reach
      complete tumor resection during surgical procedure. In case of an incidental
      tumor after simple cholecystectomy, hepatic wedge resection and lymph node
      dissection should be performed in T2 stage and above.

PMID- 9574337
TI  - [Extent of resection in surgical therapy of central bile duct carcinomas].
AB  - The introduction of a radical procedure, the extended bile-duct resection, into
      the surgical treatment of hilar cholangiocarcinoma significantly increased the
      rate of curative resections (92% versus 62% after partial hepatic resection; p <
      0.05). A comparable effect with respect to survival figures after curative
      resections did not become evident. Therefore, the true potential of this extended
      surgical procedure remains to be established.

PMID- 9574338
TI  - [Intrahepatic pressure, oxygen partial pressure and pain in chronic
      pancreatitis].
AB  - We investigated the relationship between pain, intraductal and parenchymal
      pancreatic pressures and oxygen partial pressure in 39 patients who underwent
      surgery for chronic pancreatitis with intractable pain. Acute pain was correlated
      with parenchymal pressure; correlation between pain and oxygen pressure could not
      be found. Since no strong correlation exists between pain and parenchymal
      pressure, we hypothesise that pressure and parenchymal factors contribute to the
      pathogenesis of pain in chronic pancreatitis.

PMID- 9574339
TI  - [Duodenum preserving resection of the head of the pancreas: a new standard
      operation in chronic pancreatitis].
AB  - Between 1972 and 1993, 298 patients with chronic pancreatitis underwent a
      duodenum-preserving pancreatic head resection (DPPHR). The early and late
      outcomes were prospectively analyzed. An operative mortality rate of 1%, a
      postoperative morbidity rate of 28.5% and a relaparotomy rate of 5.7% for the
      DPPHR were competitive with the rates for Whipple resection. After a median late
      follow-up of 6 years (range: 1 to 22 years), late mortality was 9%; 88% of the
      patients had no or infrequent episodes of pain and 63% were completely
      rehabilitated professionally. Only 6 patients developed diabetes mellitus early
      postoperatively. Our study proves that the duodenum-preserving pancreatic head
      resection provides better results than the Whipple resection. Therefore, this
      operation should be adopted as a new standard operation in patients with chronic
      pancreatitis.

PMID- 9574340
TI  - [Left pancreatic resection in chronic pancreatitis--with or without
      splenectomy?].
AB  - We recommend preserving the spleen in distal pancreatic resection for chronic
      pancreatitis, because it has no higher risk for complications, such as bleeding,
      and has the same hospital mortality compared with the distal pancreatic resection
      with splenectomy.

PMID- 9574341
TI  - [Oncologic risk in pylorus preservation in resection of ductal pancreas
      carcinoma].
AB  - We detected peripyloric lymph node metastasis in 2 of 24 patients with ductal
      adenocarcinoma of the pancreas who underwent Kausch-Whipple's procedure. The
      resection would have been palliative if these patients were treated by pylorus
      preserving pancreatoduodenectomy.

PMID- 9574342
TI  - [Phenotypic analysis in colorectal carcinoma: an international interdisciplinary
      project].
AB  - An European research network grouping surgeons, pathologists, biochemists and
      molecular biologists is presented. The aim of this network is to define new
      diagnostic, prognostic and therapeutic markers at protein and RNA levels in
      colorectal cancer. The methodology is based on specific sample preparation
      techniques, allowing the isolation of pure epithelial cells, and on differential
      display techniques, such as two-dimensional polyacrylamide gel electrophoresis
      (2D-PAGE) and reverse arbitrarily-primed polymerase chain reaction (RAP-PCR).

PMID- 9574343
TI  - [Locoregional recurrence of colonic carcinoma: prognosis after surgical therapy].
AB  - In a retrospective study, we analyzed prognostic factors in 143 patients with
      locally recurrent colonic cancer (excluding rectal cancer). We saw no influence
      of primary tumor state on long-term survival. In patients with curative resection
      the 5(3)-year probability of survival was significantly better than in patients
      with local palliative resection [45% (50%) vs. 5% (0%)]. In addition, we found
      striking differences in perioperative mortality which varied with therapeutic
      intention (37% for local palliative operations without resection, 16% in cases
      with palliative surgery with resection). No patient died after curative tumor
      resection.

PMID- 9574344
TI  - [Pelvic exenteration--indications, radical nature and follow-up demonstrated with
      33 clinical cases].
AB  - From March 1983 to March 1997, 24 posterior pelvic exenterations and 9 total
      pelvic exenterations were performed in 18 patients with recurrent cancer and 15
      patients with primary cancer. In 85%, we saw major complications, 78% in primary
      operations and significantly higher--96%--in recurrent cancer operations. R0
      resections we figured out in 67% of primary operations and 40% of recurrent
      operations. We saw recurrent cancer in 45% of the patients with a mean follow-up
      of 18.2 months.

PMID- 9574345
TI  - [The efficacy dilemma].
AB  - Effectivity and efficiency of medical treatment have conflicting aims which
      result in a conflict of interests between a patient, interested in maximal
      effectively and the society, interested in maximal efficiency. The physician
      cannot solve this conflict because he is primarily obliged to the interests of
      the individual patient. If rationing is unavoidable in modern health care
      services, there must be an open discussion in order to reach a broad consensus
      within the society.

PMID- 9574346
TI  - [Multimodal therapy concept in metastatic carcinoid of the gastrointestinal
      tract].
AB  - Carcinoid tumors are very rarely seen. We have treated 10 patients with carcinoid
      tumors in the last 4 years. We used arterial chemo-embolisation, embolisation,
      hepatic arterial ligature and a drug therapy with octreotide and interferon alpha
      after the resection of the primary tumor.

PMID- 9574347
TI  - [Changes in lung function after cholecystectomy--open versus laparoscopic
      cholecystectomy].
AB  - Impairment of respiratory function after open cholecystectomy may cause
      atelectasis and hypoxemia. Clinical experience shows evidence for easier recovery
      after laparoscopic operation. Postoperative respiratory function using
      spirometric tests was assessed in 50 patients with simple symptomatic
      cholecystolithiasis submitted either to open or laparoscopic cholecystectomy and
      revealed less impairment of respiratory function in the laparoscopic group.

PMID- 9574348
TI  - [Does pneumoperitoneum in laparoscopic intervention induce additional stress on
      elderly patients?].
AB  - Although the required pneumoperitoneum for laparoscopic cholecystectomy and
      laparoscopic hernial repair means stress for the elderly, it does not affect them
      negatively from a clinical point of view. On the contrary, the patient profits by
      a low complication rate, a quick recovery and a shorter stay in hospital.

PMID- 9574349
TI  - [Bile duct injuries in laparoscopic cholecystectomy--assessment of current
      status].
AB  - The laparoscopic technique for cholecystectomy is associated with a increased
      rate of bile duct injuries. A conscientious preparation, the excessive
      application of electrocoagulation, anatomical variants and renunciation of
      cholangiography are reasons for injuries. The technique of operative treatment
      depends on type, range and location of injury.

PMID- 9574350
TI  - [Trocar complications and technical aspects for prevention in laparoscopic hernia
      operation (TAPP and TPP)].
AB  - By comparing trocar-related complications in laparoscopic hernia repair in two
      series, we can demonstrate a lower rate of complications if blunt trocars were
      used. In 238 procedures using cutting trocars, we registered 2 major
      complications and 9% of local hematoma.

PMID- 9574351
TI  - [Laparoscopic transperitoneal inguinal hernia repair (TAPP)--complications and
      results of a prospective study].
AB  - Results of a prospective study of 776 TAPP procedures performed on 600 patients
      are reported. We found rates of 0.5% for intraoperative complications and 1.3%
      for early-postoperative complications. Late postoperative complications have been
      observed in an incidence of 4.4% for haematomas, 7.9% for scrotal discomfort,
      1.2% for hyperaesthesia and trocar hernias have occurred in 0.9%. The recurrence
      rate was 3.9%. Results suggest that improvement of the technique of laparoscopic
      hernia repair may prevent complications and may lower future complication rates.

PMID- 9574352
TI  - [Implantation metastases in incidental gallbladder carcinoma after laparoscopic
      cholecystectomy].

PMID- 9574353
TI  - [Intraperitoneal tumor seeding in colorectal carcinoma surgery--follow-up of a
      comparison of laparoscopic versus open procedure].
AB  - Follow-up 71 patients during 20 months (12-29) operated on for colorectal cancer
      by laparoscopic or open surgery demonstrated no correlation between port-side
      metastases (1/35) or tumor recurrences (5/71) and intraperitoneal tumor cells.
      All these patients were cytologic-negative; however, all were initial in an
      advanced tumor stage (pT3-4, N1-3). We conclude from these results that free
      tumor cells during operation do not seem to influence outcome or the development
      of port-side metastases.

PMID- 9574354
TI  - [Standardization in sigmoid diverticulitis surgery planning: indications based on
      evaluation with the Hughes classification].
AB  - Sigmoid diverticulitis accounts for the most frequent colonic disease in Western
      countries. We studied 145 patients with diverticulitis (elective resection in
      105, emergency resection in 40 patients) using the HUGHES classifications-based
      indication of the resection procedure (Stage I, acute diverticulitis/colonic wall
      phlegmonia, continent resection; Stage II, perforated diverticulitis with local
      perotinitis, continent resection, Hartmann's procedure exceptionally; Stage
      III/IV, Hartmann's procedure, continent resection exceptionally). Stage-specific
      morbidity was I: 18%, II: 22%, III/IV: 60%; emergency case mortality was 15%;
      elective case mortality was 0%. Severe local failure was significantly higher in
      stage II/IV than stage II/I class diverticulitis. Early elective resection is
      recommended with regard to morbidity, mortality, and hospitalisation time and
      related costs.

PMID- 9574355
TI  - [Surgery of Crohn disease in the course of time--a retrospective analysis of
      1,044 operations].
AB  - In 591 patients with Crohn's disease, 1044 operations were performed within 16
      years. The aim of this study was to evaluate the changes in treatment time,
      indication for surgery, surgical technique, and postoperative complications.
      There was a significant reduction in treatment time (in-patient), whereas the
      number of operations in general increased. The frequency of emergency operations
      has declined. The postoperative complication rate did not change, but there was a
      correlation between emergency operation and the complication rate. Surgery for
      perforating Crohn's disease, acute intestinal obstruction or intra-abdominal
      abscess also correlated with a significantly higher complication rate.

PMID- 9574356
TI  - [Rectum replacement by colon reservoir: good quality of life thanks to minimal
      morbidity?].
AB  - Surgery of rectal cancer aims at providing satisfactory quality of life at an
      early postoperative stage. Low postoperative morbidity and good defecation
      quality early after rectal reconstruction by means of a colonic reservoir are
      essential conditions for good quality of life.

PMID- 9574357
TI  - [Extraperitoneal, "tension free" inguinal hernia repair with local anesthesia--a
      contribution to effectiveness and economy].
AB  - In this present randomized controlled study, two groups, each consisting of 45
      patients, underwent tension-free inguinal hernia repair under general versus
      local anesthesia. Patients in the local anesthesia group described their pain
      during mobilisation by using the VAS and were found to have a significant pain
      level decrease from the first to the fifth postoperative day. In conclusion, it
      could be shown that tension-free hernia repair under local anesthesia is superior
      to tension-free hernia repair during general anesthesia concerning perception of
      pain and pain management.

PMID- 9574358
TI  - [Extraperitoneal cicatricial hernia repair with implantation of non-resorbable
      synthetic mesh].
AB  - Large incisional hernias and recurrences were treated by extraperitoneal
      implantation of polypropylene mesh using a sublay technique in 37 patients. There
      were 10 minor (5 haematoma, 3 seroma, 2 patients with postoperative increased
      temperature) and 2 major complications (1 case of skin necorsis, 1 deed wound
      infection with fistulation and involvement of mesh). Within a mean follow-up time
      of 17 months, we saw 3 recurrences.

PMID- 9574359
TI  - [Value of preoperative diagnosis in struma surgery].
AB  - To determine the usefulness of so-called routine diagnostic procedures prior to
      thyroid operations, in 2007 consecutive patients undergoing thyroid surgery from
      1976 until 1991, the results of 1833 scintigraphy examinations, 1358 tracheal X
      rays, 773 ultrasound examinations, 302 fine-needle aspiration biopsies (FNAB),
      and 73 frozen sections (FS) performed during operation were evaluated.
      Scintigraphy and ultrasound showed similar positive predictive values, ranging
      between 85% and 95%, in detecting thyroid nodules. The sensitivity of FNAB and FS
      were 44% and 83%, respectively. Mechanical alteration of the trachea was found to
      correlate to a high degree with severe postoperative respiratory disorders,
      requiring prolonged ventilation or tracheotomy either during primary surgery or
      as a secondary procedure.

PMID- 9574360
TI  - [Does decreased preoperative diagnosis in goiter surgery present special
      challenges for the surgeon? What stays indispensible? What is superfluous?].
AB  - Patient history, clinical examination, basal TSH, and ultrasound are the crucial
      factors for the indication of surgical treatment of the goiter. In our study,
      additional scintiscan failed to locate additional nodules found by intraoperative
      digital examination of the thyroid in 10.3%, and therefore leads to no additional
      security in determining the extent of thyroid resection (exception: autonomous
      goiter). Intraoperative inspection and palpation of both thyroid lobes remains
      the most important factor in preventing goiter recurrence.

PMID- 9574361
TI  - [Is preoperative scintigraphy in euthyroid nodular goiter necessary?].
AB  - Preoperative thyroid isotope scan would influence the operative procedure and the
      perioperative management in patients with nontoxic goiter only if it raises
      suspicion of malignancy. However, the scintigram shows significantly lower
      sensitivity and specificity in the detection and prediction of malignant nodules
      in the thyroid gland than the ultrasound examination. Thyroid isotope scan is
      more expensive than ultrasonography, and its routine use in the investigation of
      nontoxic nodular goiter should be abandoned.

PMID- 9574362
TI  - [Value of fine needle puncture cytology, thyroid gland ultrasound and thyroid
      gland scintigraphy in diagnosis of thyroid carcinomas].
AB  - Szintigraphy of the thyroid gland is still one of the most important preoperative
      diagnostic procedures. Ultrasound of the thyroid gland is a highly sensitive, but
      less specific method. Fine-needle aspiration as an additional diagnostic method
      has a higher specificity in the case of a positive result.

PMID- 9574363
TI  - [Intraoperative determination of parathyroid hormone--an alternative to
      preoperative localization diagnosis].
AB  - The results of localization procedures in hyperparathyroidism are not satisfying
      and amount to 65% for ultrasonography, 63% for CT-scan, 75% for MRI, and 74% for
      Tc-Mibi scintigraphy. Since 1994, we have performed intraoperative measurement of
      PTH with a modified immunochemiluminiscence assay in 44 patients. Ten minutes
      after exstirpation of pathological parathyroid glands, the PTH concentration
      decreases to less than 40% of the starting PTH level. We think that
      intraoperative PTH measurement is a rapid and safe method for controlling the
      success of surgery in HPT and makes preoperative localization procedures
      unnecessary.

PMID- 9574364
TI  - [Unilateral neck exploration in primary hyperparathyroidism].
AB  - Within a prospective case control study from 1993 to 1996, in 85 first operations
      for primary hyperparathyroidism the neck exploration was ended unilaterally when
      an adenoma (also histologically proven) and one normally small parathyroid gland
      were found. Otherwise or in case of simultaneous surgery of the thyroid gland, a
      bilateral exploration was performed. The primary success rate with this strategy,
      additionally based on 69.4% correct results of cervical ultrasound, was 95.3%,
      with a significant saving of an average of 30 min. operating time.

PMID- 9574365
TI  - [Calcium metabolism after thyroidectomy with modified radical neck dissection and
      parathyroid gland autotransplantation].
AB  - The issue of parathyroid autotransplantation in oncologic thyroid surgery is
      discussed controversially. In a series of 15 patients who underwent bilateral
      modified radical neck dissection for thyroid malignancy, parathyroid
      autotransplantation was carried out. Six months after surgery only one patient
      was hypoparathyroid, requiring permanent medication, thus autotransplantation is
      a safe procedure for the prevention of accidental hypoparathyroidism.

PMID- 9574366
TI  - [Introduction of laparoscopic cholecystectomy in Albania from an economic
      viewpoint].

PMID- 9574367
TI  - [How expensive is treatment of reflux disease?].
AB  - In a prospective documented series of reflux patients, a retroelective analysis
      of medication cost and duration of conservative therapy as well as the costs for
      surgical therapy including preoperative diagnostic workup, cost during
      hospitalization, and costs for complications with necessary additional treatment
      and readmissions is assessed. Cost-relevant factors are in conservative treatment
      cost-relevant factors are those patients who need increasing dosages, while in
      surgical treatment the cost-relevant patients are those with complications who
      need additional treatment.

PMID- 9574368
TI  - [Use of preoperative infusion cholangiography before laparoscopic
      cholecystectomy].
AB  - In the present study, we intend to evaluate whether intravenous cholangiography,
      performed on a routine basis in the preoperative period, in addition
      ultrasonography, history or elevations of serum bilirubin and alkaline
      phosphatase, provides any supplementary information in detecting patients with
      asymptomatic calculi in the common bile duct before laparoscopic cholecystectomy
      is carried out. Therefore, 513 patients were included in a retrospective
      analysis. From our data, we conclude that preoperative intravenous
      cholangiography cannot be recommended, when costs and risks and a potential
      benefit for the patient are considered.

PMID- 9574369
TI  - [Laparoscopic versus open cholecystectomy in therapy of acute cholecystitis].
AB  - In patients with acute cholecystitis, hospital stay, blood loss, operative time
      and perioperative risk are compared for open and laparoscopic operations. There
      is a trend to wards a reduced hospital stay without any increased risk for
      patients with laparoscopy if critical patients are operated open.

PMID- 9574370
TI  - [Laparoscopic gastrostomy--advantages in comparison with percutaneous endoscopic
      gastrostomy (PEG)].
AB  - Laparoscopic gastrostomy was performed on 70 patients with contraindications to
      PEG. All procedures were performed successfully, even in patients with gastric
      resections, after gallbladder surgery, and in patients with liver cirrhosis and
      ascites. Long-term results comprise a low complication rate of 0.12 in 100
      application days. Laparoscopic gastrostomy is a highly effective procedure with
      low morbidity and good long-term results in patients with contraindications to
      PEG requiring enteral feeding.

PMID- 9574371
TI  - [Laparoscopic palliative gastrointestinal operation in inoperable upper abdominal
      tumors with gastric outlet obstruction].
AB  - In the period from June 1994 to February 1997, a laparoscopic gastroenterostomy
      was carried out without intraoperative complications or mortality. In 12 out of
      13 patients with gastric outlet obstruction due to inoperable tumor of the upper
      GI tract (gastric, gallbladder or pancreas carcinoma). From the above, a total of
      4 patients had postoperative complications (30.7%), three of which could be
      treated without further operation. The average duration of the operation was 130
      min (range 70-285 mins) followed by an approximal postoperative hospital stay of
      17 days (8-41 days).

PMID- 9574372
TI  - [Current status of laparoscopic colorectal surgery--a nationwide survey].
AB  - Fifteen percent of all departments of surgery in Germany have experience with
      laparoscopic colorectal operations. Of the overall number of 143,000 cases, only
      about 1% were performed minimally invasively.

PMID- 9574373
TI  - [Laparoscopic staged lavage in CAPD catheter peritonitis--an alternative to open
      treatment?].
AB  - Three patients suffering from severe CAPD peritonitis underwent laparoscopically
      programmed lavage after removal of the catheter. After an average of four
      laparoscopic lavage operations all patients had to be treated using conventional
      open procedures; a mean of ten programmed lavage procedures were carried out
      because of increasing peritoneal inflammation and worsening of the clinical
      situation during minimal invasive therapy. One patient did not survive.
      Laparoscopic treatment is thus not recommended for diffuse peritonitis.

PMID- 9574374
TI  - [Ulcer hemorrhage: is aggressive surgical therapy still defensible?].
AB  - A total of 155 patients admitted with Forrest 1a/2a peptic ulcer bleeding were
      prospectively recorded. Primarily conservatively treated patients developed
      recurrent bleeding in 27.4% of cases, with a mortality of 10.5% compared to 8.7%
      mortality after early elective surgery. In our opinion, the indication for
      surgery has to be reassessed in patients with Forrest 2a peptic ulcer bleeding.

PMID- 9574375
TI  - [Potential for improvement of combined endoscopic-surgical treatment of bleeding
      gastroduodenal ulcer].
AB  - A total of 119 patients (January 1995-December 1996; 53 women, 66 men) with a
      medium age of 63.1 years were admitted to hospital with bleeding gastroduodenal
      ulcer. Emergency gastroduodenoscopy was performed immediately in all cases,
      sclerotherapy in 94 cases (78.9%). Control endoscopy was done routinely after 12
      24 h; the recurrent bleeding rate amounted to 14.3%, mortality was 5%, and
      surgical intervention was necessary in 8.4% with a mortality of 40% (!).

PMID- 9574376
TI  - [Role of sonography as primary diagnostic method in acute abdomen--a prospective
      study].
AB  - A prospective study of 584 consecutive patients presenting with acute abdominal
      pain was conducted to evaluate the role of ultrasonography as a first-line
      diagnostic tool for differentiating between surgical and nonsurgical diseases.
      The study reveals a high sensitivity and specificity for the diagnosis of
      diverticulitis, cholecystitis, and bowel obstruction. In acute appendicitis the
      method is highly specific, but the sensitivity is rather low. Taking into account
      the high rate of specific results, routine ultrasonography can be recommended as
      a screening method in patients suffering from acute abdominal pain.

PMID- 9574377
TI  - [Is perforating appendicitis a separate disease picture?].
AB  - Large epidemiological studies recently published suggest that perforating
      appendicitis may represent a separate disease entity. To find out whether
      perforating and nonperforating appendicitis may be distinguished by clinical
      features (history and examination, lab tests) data from 519 cases of acute
      appendicitis (17.7% perforations) were analysed, and significant differences were
      recorded in various aspects of history and clinical examination. It was concluded
      that perforating and nonperforating appendicitis may clinically be distinguished
      reliably in the majority of cases.

PMID- 9574378
TI  - [Discontinuity resection in therapy of complicated sigmoid diverticulitis].
AB  - A total of 112 patients were operated on for severe complicated sigmoid
      diverticulitis, Hartmann's procedure was performed due to local or generalised
      peritonitis, 80% to them as emergency surgery. There was a mortality of 18.8% due
      to the sepsis or other complications. Sixty-two of the remaining 80 patients
      underwent a restorative procedure without any mortality and low morbidity (11
      died after discharge not related to the colon disease). Resection and primary
      anastomsis is always the first choice, but in cases of severe peritonitis there
      is no discomfort or risk for the patient if Hartmann's procedure with restorative
      surgery is chosen.

PMID- 9574379
TI  - [Ultrasound-controlled, percutaneous drainage: a safe and simple method for
      treatment of intra-abdominal abscesses].
AB  - Ultrasound-guided percutaneous catheter drainage is useful in the diagnosis and
      treatment of intra-abdominal abscesses. The indication depends on the
      localisation and cause of the abscess. Keeping the indications, we treated 62
      patients with ultrasound-guided percutaneous catheter drainage and recorded a
      primary success of 90% and no severe complications such as bleeding or bowel
      perforation.

PMID- 9574380
TI  - [Surgical therapy of primary breast carcinoma--options and perspectives].
AB  - During the past quarter of the century the management of breast cancer has been
      dramatically influenced by new ideas and discoveries which, after being tested in
      controlled studies, govern current clinical practice. New therapeutic options are
      discussed, and first results are presented. The following procedures are
      illustrated: Van Nuys Classification of DCIS, skin-sparing mastectomy,
      stereotactic biopsy (ABBI), endoscopic axillary dissection, fluorescentic
      detection of positive lymph nodes, sentinel lymph nodes. Neoadjuvant
      chemotherapy, and menstrual cycle-dependent timing.

PMID- 9574381
TI  - [Therapy of the small breast carcinoma--generalized conversion to breast-saving
      treatment in Germany. 8 years results].
AB  - In the prospective nonrandomized observation study "Therapy of Small Breast
      Cancer", which was the first multicenter trial on breast cancer ever conducted in
      Germany, mastectomy (303 cases) was compared with breast-preservation therapy
      (733 cases) in patients with stage pT1N0M0 breast cancer. After a median follow
      up of 8 years, there is no difference between the treatment modalities with
      regard to disease-free and overall survival which compares well with the results
      of international randomized studies. There is no difference in treatment outcome
      between centers specialized in the therapy of breast diseases in comparison to
      less experienced institutions as long as a high standard of treatment performance
      is guaranteed by reference centers.

PMID- 9574382
TI  - [Minimal invasive surgery in clinically occult breast carcinoma].
AB  - The ABBI (Advanced Breast Biopsy Instrumentation) system is a new method of
      breast surgery of nonpalpable tumors which permits intraoperative mammography. In
      a pilot study it was shown that a small carcinoma can be removed by a
      mammographically and stereotactically controlled biopsy (20 mm maximum diameter).
      An indicated breast-conserving therapy can be carried out when using this method.

PMID- 9574383
TI  - [Lymph drainage as prognostic factor in breast carcinoma].
AB  - Lymph stasis detectable by means of breast lymphography and which developed as a
      consequence of axillary lymph node metastases has proved to be a valuable factor
      in the prognosis of breast cancer. As with secondary lymphedema, lymph vessels
      were found to be dilated, which was regarded as a consequence of tumoral
      obstruction, and the elevated pressure in these lymph vessels may cause
      hematogenous spread of the tumors through venous shunts. Significant correlation
      between preoperative lymphographic findings and the incidence of distant forming
      5 years postoperatively was also found, which leads to the conclusion that the
      distant metastases exist prior to the operation can account for the late tumor
      recurrence.

PMID- 9574385
TI  - [Expanding the indications spectrum for breast saving therapy of breast carcinoma
      by oncoplastic operations].
AB  - Esthetically unfavorable results may occur in 15%-20% after breast-conserving
      therapy for breast carcinoma. With increasing experience, plastic reconstructive
      techniques have evolved for reconstructing even large parenchymal defects after
      segmentectomy or in adverse tumor sites with esthetically reliable results. This
      had led to an expansion in the indication for breast-conserving therapy.

PMID- 9574386
TI  - [Simulation of in vivo study conditions for comparing the possibilities and
      limits of mammography in various breast implants].
AB  - Especially in breast reconstruction after mastectomy, subcutaneous mastectomy, or
      extensive lumpectomy, the radiological properties of breast implants play an
      important role. Mammography is still the gold standard for follow-up diagnostics
      as well as for preventive diagnostics, and the interpretation of these films is
      greatly influenced by the type of the implant filler material. In this study, in
      vivo conditions are simulated, and standard mammography techniques applied to
      examine the effects of various types of implants on the readability of
      mammography films using semiquantitative measurements as well as subjective
      judgement by independent radiologists.

PMID- 9574387
TI  - [Optics with natural appearing added illumination].
AB  - Today's endoscopes use a central frontal illumination which creates huge
      contrast, no visible shadows, and gives an unnaturally flat impression. In the
      SIMIC project, a new type of optics has been developed that uses additional
      illumination fibres ending 3 mm behind the front lens. This gives a more natural
      and spatial impression of the body cavity, causes shadows that are an improvement
      when approaching tissue with an instrument, reduces blooming in the foreground,
      and improves detail reproduction in the background.

PMID- 9574384
TI  - [Sentinel node biopsy, a step toward selective axillary dissection].
AB  - We studied sentinel lymph node detection in 69 patients with breast cancer. A
      sentinel node (SN) was detected in 58 patients (83%), and the pathological result
      was compared with the results of the axillary contents. We found a positive
      correlation of the pathological results of the SN in relation to the axillary
      contents in 96% in pT1 and pT2 tumors.

PMID- 9574389
TI  - [Initial experiences with the modular retraction system (VarioLift) for
      laparoscopic surgery without pneumoperitoneum].
AB  - The VarioLift system is an alternative method for abdominal wall lifting to
      create sufficient intra-abdominal space and adequate laparoscopic exposure to the
      operating field. The installation of a CO2 pneumoperitoneum is not necessary,
      which means that technical disadvantages, systemic and local physiological
      effects, or complications related to gas insufflation are not relevant when this
      method is used. The surgeon is allowed to combine the advantages of endoscopic
      surgery, such as magnified video-endoscopic visualisation, with well-known open
      surgical techniques to create a symbiosis of prove methods.

PMID- 9574390
TI  - [Laparoscopic-gastroscopic intragastric stomach surgery].
AB  - In three cases, a new technique for intragastric surgery were used. The ports
      were placed using a step system (blunt trocars) directly into the stomach. In two
      cases, a benign tumor was resected, and we converted one case of bleeding.

PMID- 9574388
TI  - [Laparoscopic instruments in practical clinical tests--prospective study of
      functional aspects and residual contamination].
AB  - Wear, tear, and possible contamination after 100 clinical cycles of three test
      trays were investigated on laparoscopic "tracer" instruments in a prospective
      clinical study. Failure was below 4 per 100 laparoscopies, and remaining
      contamination was detected after passing 100 cycles in 20%, which happened to
      control instruments from open surgery as well. Further clinical data of
      contamination levels for apparently clean instruments must be collected to
      evaluate and correlate to microbiological testing.

PMID- 9574391
TI  - [Strategy and outcome in bowel injuries after blunt abdominal trauma].
AB  - In this retrospective trial, we examined 215 patients with bowel lesions
      following abdominal injuries. We analyzed the diagnostic procedures, the time to
      diagnosis, the subsequent surgical therapy, and complications. The diagnosis of
      bowel lesions remains a diagnostic challenge. All apparative diagnostic
      procedures (sonography, CT-scan, lavage, laparoscopy, X-ray) fail to diagnose
      bowel lesions. In our trial, most patients showed clinical signs of peritonitis
      leading to diagnosis. Ultrasonographically guided puncture was important, if
      clinical signs remained unclear. This study underlines the importance of repeated
      clinical examination for early diagnosis and treatment of bowel injury.

PMID- 9574392
TI  - [Outcome of primary surgical management of liver trauma].
AB  - We evaluated retrospectively 43 patients with liver trauma undergoing laparotomy
      between 1/89 and 12/95. Blunt trauma (27 patients) and penetrating trauma (16
      patients) to the liver had a mortality of 37% and 0%, respectively. The overall
      mortality was 23.3% and was significantly related to concomitant injuries (p =
      0.002), whereas age, severity of the liver trauma as well as the surgical
      treatment had no significant influence on the outcome.

PMID- 9574393
TI  - [Selection criteria for conservative therapy of splenic trauma in adults].
AB  - The safety and effectiveness of nonoperative management of selected adults have
      been confirmed in those patients who meet selection criterias of isolated splenic
      injury and hemodynamic stability. The CT scan is a very precise and the most
      specific diagnostic procedure in splenic trauma. Nonoperative treatment is
      successful in 80% of adults in such selected group of patients.

PMID- 9574395
TI  - [Early infection after surgical fracture treatment: therapy with reference to
      socioeconomic aspects].
AB  - Early postoperative infection following open reduction and internal fracture
      fixation is the most serious complication in orthopedic surgery. The
      transformation of an acute osteitis into a chronic form marks the central
      problem. Every single case of chronic osteitis represents an economic disaster.

PMID- 9574394
TI  - [Measuring epidural intracranial pressure in patients with severe craniocerebral
      trauma].
AB  - In 30 patients with severe head injury (SHI), intracranial pressure (ICP) was
      monitored using epidural transducers. In 22 patients, the measurements were
      reliable, with average values of 19.4 mmHg in the survivors and 64.6 mmHg in
      those who died. It is concluded that epidural measurement of ICP provides a
      helpful method for the management of SHI and to control the indication for CT
      scans.

PMID- 9574396
TI  - [Distal tibial fracture--an indication for osteosynthesis with the unreamed
      intramedullary nail?].
AB  - In a prospective study, 50 fractures of the distal fifth of the tibia with
      additional involvement of the ankle joint in 18 patients were stabilized by
      unreamed nailing. In all, 90% of all fractures healed uneventfully without
      further surgical intervention after unreamed nailing, the highest ratio of
      complications (22%) being seen in all patients with distal fractures of the
      fibula without additional plating (of the fibula). Tibial fractures close to the
      ankle joint can be managed by unreamed nailing; distal fractures of the fibula
      should be additionally stabilized by fibular plating.

PMID- 9574397
TI  - [Acromioclavicular joint injuries: efficient therapy from the economic
      viewpoint].
AB  - The results of surgical treatment with tension band wiring versus conservative
      therapy with bandages are described in a retrospective study. Operative therapy
      is associated with complications in 32.3% and two occasions of hospitalisation.
      The advantages of conservative therapy are obvious: it is easy and comfortable
      for the patient; there are no complications and low costs, and it is associated
      with a shorter temporary disablement. Therefore, conservative therapy is our
      standard, and surgery is performed only for Rockwood IV-VI lesions and in
      exceptional cases.

PMID- 9574398
TI  - [The trauma register of the 'Polytrauma' Committee of the German Society of
      Trauma Surgery as the basis for quality management in the management of severely
      injured patients].
AB  - The data of 1037 severely injured patients (mean ISS = 20) from 15 clinics were
      centrally and prospectively collected in the Trauma Registry of the German
      Society of Trauma Surgery and analyzed anonymously. Significant differences in
      respect to the treatment criteria (i.e., duration of basic diagnostics in severe
      trauma) and quality of outcome (TRISS method and Z statistic) were revealed for
      some clinics. The feedback of their data offers the associated clinics the
      possibility of identification of treatment phases that are worth being optimized.

PMID- 9574399
TI  - ["Score systems as a measure for quality assurance in polytrauma?"].
AB  - Score systems in trauma try to aggregate the severity of injury in a single
      number of formula. They give a common basis to standardize logistics and outcome
      in trauma management. This holds true only if the score is valid, reliable, and
      based on a meticulous documentation of data. As errors cannot be excluded,
      individual decisions in trauma management can never rely on scores alone.

PMID- 9574400
TI  - [Evaluation of the severity of thoracic injuries and their significance for post
      traumatic outcome--a retrospective study of1,326 patients].

PMID- 9574401
TI  - [Value of mediastinoscopy versus thoracic CT for prediction of mediastinal tumor
      lymph nodes].
AB  - The value of mediastinoscopic staging in bronchial carcinoma is evaluated
      controversially. The literature gives a wide range of specificity of CT scans,
      varying from 30%-100% and 29%-95%, respectively [1, 2, 3]. We have reviewed a
      consecutive series of 182 patients who underwent a high-resolution mediastinal CT
      scan followed by mediastinoscopy (MS) because of pulmonary or mediastinal
      disease. The specificity of CT versus MS revealed 32% versus 100% and the
      sensitivity 47% versus 74%. Although we have observed complications and a limited
      histological prediction in the MS within the paratracheal area on the left side,
      we continue to recommend a standard staging MS, taking this area into careful
      consideration.

PMID- 9574402
TI  - [CT angiography of the pulmonary artery in patients with bronchial carcinoma].
AB  - The aim of the study was to evaluate 3D computed tomography (3D-CT) for the
      visualization of tumor extent with respect to the infiltration of the pulmonary
      arteries in patients with locally advanced small and nonsmall-cell lung cancer. A
      total 61 examinations in 40 patients with bronchial carcinoma were performed with
      contrast-enhanced (150 ml injected with 4 ml/s after bolus tracking) 2 mm spiral
      CT (pitch 1.5, increment 1 mm) (Somatom Plus4, Siemens AG, Germany). Using the
      implemented software cine mode, surface shaded display (SSD), and maximum
      intensity projection (MIP), reconstructions of the pulmonary arteries and the
      tumors were generated. In comparison to conventional spiral thoracic CT, the
      optimized cross-sectional images of the mediastium represented a benefit with the
      technique described, and this can help to diagnose vessel infiltration and may
      therefore be of value for pre- and post-therapeutic staging in modern stage
      adapted multimodality treatment programs.

PMID- 9574403
TI  - [Thoracoscopy is a reliable alternative to thoracotomy in peripheral lung coin
      lesion].
AB  - Video-assisted thoracoscopy (VATS) is useful for improving preoperative diagnosis
      and staging in patients with peripheral pulmonary lesions. Additional information
      obtained by VATS had a major influence on the therapeutic strategy in 34% of the
      patients, and in 39% of the patients in the conventional surgery group
      thoracotomy could possibly have been avoided if VATS had been available.

PMID- 9574405
TI  - [Hyperhidrosis of the upper extremity: long-term outcome of endoscopic thoracic
      sympathicotomy].
AB  - A total of 630 endoscopic thoracal sympathicotomies were performed for
      hyperhidrosis of the upper limbs, and complications and success rates were
      analyzed after a median follow-up period of 16 years (83% of patients). In all,
      67.8% of patients were fully satisfied, 25.7% were partially satisfied and would
      again agree to the operation, and 93% the procedure terminated hyperhidrosis
      permanently. Compensatory and gustatory sweating was observed in 67% und 47% of
      cases, respectively, impairing the patients satisfaction. Overall success was
      significantly (p < 0.001) lower in the group with axillary hyperhidrosis.

PMID- 9574404
TI  - [Bilateral video-assisted thoracoscopic volume reduction surgery for treatment of
      advanced pulmonary emphysema].
AB  - In a prospective study, we investigated the functional results, complications,
      and survival of patients who underwent bilateral video-assisted thoracoscopic
      (VAT) lung volume reduction surgery (VRS) for severe, diffuse pulmonary emphysema
      (FEV1 0.77 +/- 0.03 [1], RV/TLC 0.65, 12' walking distance 482 +/- 26 [m]). From
      January 94 to March 97, 67 of 179 candidates underwent the operation, and 58
      patients (mean age 64 +/- 1.1, range 42-78 years; 17 women) fulfilled the study
      criteria. There was no 30-day mortality; hyperinflation decreased to an RV/TLC
      ratio of 0.52 +/- 0.01 after 3 months; FEV1 increased to 1.2 +/- 0.08 [1]; and
      the 12' walking distance was 687 +/- 29 [m].

PMID- 9574406
TI  - [Cost comparison of minimal invasive surgery vs. standard operation exemplified
      by primary pneumothorax].
AB  - In patients with primary spontaneous pneumothorax, the costs for a minimally
      invasive operation were retrospectively compared with the costs for a standard
      operation using lateral thoracotomy. The calculations were based on the direct
      costs for the operation, the expenditures for the in-hospital stay, and the
      socioeconomic costs in terms of working disability. The results demonstrate that
      the high expenses for the minimally invasive operation are compensated by the
      reduction in costs due to a shorter in-hospital stay and a shorter recovery time
      in patients treated by minimally invasive surgery.

PMID- 9574407
TI  - [Can the reliability of sensory evoked potential monitoring during carotid artery
      surgery be improved?].
AB  - Neurological monitoring during endarteriectomy of the internal carotid artery is
      essential, especially while operating without shunt. In our own department, SEP
      monitoring was improved by the introduction of so-called Farfield Analysis of
      evoked potentials. Since the introduction of Farfield Potential Measurement, no
      recognizable neurological deficit has been evident.

PMID- 9574408
TI  - [Quality assurance in carotid artery surgery pre-, intra- and postoperative].
AB  - In our clinic, quality control and the need for safety are an integral part of
      the clinic's daily regime. For every kind of arterial reconstruction, independent
      of its locality, we have developed clinical standards and guidelines, which make
      our procedures transparent, comparable, and evaluable. For every assistant in our
      educational establishment, these standards have become a fixed guideline for
      adequate therapeutic treatment.

PMID- 9574409
TI  - [Carotid endarterectomy in the early phase after a non-disabling stroke: 1980
      1995 results].
AB  - In 56 patients, carotid endarterectomy (CEA) was performed 14 days (median) after
      a non-disabling carotid-related stroke with a perioperative minor stroke rate of
      3.6%. Even large ischemic brain infarcts on CT scan did not exclude patients from
      CEA, as long as the patient had reached a neurologic plateau. The data from this
      study indicate that CEA can be performed safely in properly selected patients,
      and might reduce the high risk of a recurrent stroke (5%-9.5% within 30 days).

PMID- 9574410
TI  - [Paraganglioma of the carotid bifurcation. Diagnostic and therapeutic strategy].
AB  - The carotid body tumors are semimalignant tumors. According to our results, the
      best diagnostic procedure is a combination of Doppler color flow imaging
      ultrasound, computed tomography and selective angiography. In our opinion, the
      treatment of choice is radical resection of the tumor with the carotid
      bifurcation, especially to reduce recurrence of the tumor. Considering the
      problems in recurrent tumors, consequent monitoring of the patients is necessary.

PMID- 9574411
TI  - [Simultaneous intervention in vascular surgery. Risk assessment and cost-benefit
      analysis].
AB  - Thirty-four simultaneous vascular operations were performed from 1993 to 1996.
      Postoperative complications were similar to additive complication rates of
      carotid endarterectomies and other vascular operations undertaken during this
      period. Operation time and postoperative hospital stay was significantly shorter,
      and cost-benefit analysis revealed clear advantages for the simultaneous group.

PMID- 9574412
TI  - [Combined interventions in transfemoral stent implantation in infra-renal
      abdominal aortic aneurysm].
AB  - The transluminally placed endovascular graft (TPEG) is a novel method for the
      treatment of abdominal aortic aneurysms (AAA). Aortobiiliacal application
      requires three anchor sites and can often not be performed in cases of aneurysm,
      occlusion, or elongation of the iliac arteries. Here the aorto-uniiliacal stent
      implantation combined with crossover bypass provides an alternative procedure,
      and thus broadens the therapeutic endovascular spectrum.

PMID- 9574413
TI  - [Intraoperative lysis and neurostimulation as added therapy in surgery of
      popliteal artery aneurysm].
AB  - Additional therapy of symptomatic popliteal artery aneurysm includes
      intraoperative lysis for the treatment of the descending thrombosis and spinal
      cord stimulation for cases of chronic deterioration of the peripheral perfusion
      state. Between 1989 and 1996, we treated 50 patients with 55 symptomatic
      aneurysms using this concept, 18 of them as emergency cases. We reached a
      postoperative amputation rate of 12.7% and good long-term functional results in
      34 of 37 patients.

PMID- 9574414
TI  - [Value of femoral bifurcation transposition for revascularization of the thigh].
AB  - Fifty-seven patients with 60 transpositions of the femoral artery bifurcation
      were prospectively analysed. This operation provided limb salvage in 95% and a
      sufficient revascularisation in 88% after the operation and 81% during follow-up
      18 (6-28) months. The transposition of the femoral artery bifurcation is a
      reasonable operation in patients with a relevant stenosis of the profunda
      femoris. It does not need alloplastic patches, the saphena vein is conserved and,
      in our series, subsequent distal bypass was required in less than 10%.

PMID- 9574415
TI  - [Iatrogenic vascular lesions as sequelae of therapeutic and invasive diagnostic
      measures].
AB  - When studying the etiology of trauma-induced injury, it is apparent that there is
      an increasing incidence of iatrogenic vascular lesions. One reason for this
      phenomenon is that many vascular procedures, including invasive catheteral
      procedures, minimally invasive interventions and osteosynthetic operations, are
      being performed more frequently. In such emergent clinical situations, prompt and
      appropriate diagnostic evaluation and reconstruction of affected vessels are
      required for a successful outcome.

PMID- 9574417
TI  - [Staging mesenteric ischemia based on histopathologic findings in the animal
      model].
AB  - With a minimal invasive access, a segmental intestinal ischemia of different
      duration was established in 25 pigs. After 24 h of reperfusion, the bowel was
      resected and examined by light microscopy. Considering these results, we
      developed a histopathological grading of intestinal ischemia to distinguish
      between viable and necrotic segments.

PMID- 9574416
TI  - [Embolism detection after carotid endarterectomy].
AB  - Embolic phenomena, early after endarterectomy of the internal carotid artery,
      were observed in 8 of 28 cases. No patient suffered from ischemic events. 24 h
      later, no further embolic signals could be detected. These and other observations
      of an increased risk of perioperative thrombosis and cerebral infarction, in the
      case of persistent embolic signals during the early recovery period, confirm the
      probably important role of the transcranial emboli detection in the monitoring of
      carotid surgery.

PMID- 9574418
TI  - [Does MRI compared with ultrasound examination add therapy-relevant knowledge in
      anorectal abnormalities?].
AB  - The topographical situation of the blind end of the recto-anal atresia to the
      musculus levator ani is the main question to ask when deciding on any operative
      procedure and for the prognosis of continence. In neonates, the use of
      preoperative perineal ultrasound is sufficient rather than magnetic resonance
      imaging in establishing the surgical way. In older incontinent children after
      pullthrough procedure, magnetic resonance imaging has benefits over endorectal
      ultrasound, especially in presenting muscular and cicatricial relationships.

PMID- 9574419
TI  - [Endosonographic determination of the volume of anal sphincter muscles as a
      parameter for continence outcome in childhood].
AB  - The volumes of the external and internal anal-sphincter muscles, determined by
      three-dimensional (3d) endosonography, are linear to each other and to the body
      height and body-surface ratios in normal children. In patients with an operation
      of the sphincter muscles, the reduced volume of the external sphincter system
      permits a differentiation of incontinent children; the volume of the internal
      sphincter muscles, however, doesn't give a significant difference nor does the
      muscle-thickness. An acceptable estimation of the sphincter muscles volume can be
      made with conventional endosonography by planimetry of the muscle tissue in four
      representative axial cut-planes and by measuring of the sphincter-length.

PMID- 9574420
TI  - [Value of anorectal manometry in assessment of constipation in childhood].
AB  - We studied retrospectively 210 anorectal manometries of constipated children. Of
      the 87 patients with an anal fissure or a functional constipation, 83 had normal
      sphincter relaxation. All of the 23 patients with Hirschsprung's disease lacked
      the sphincter relaxation, as well as 22 of the patients with a dysganglionosis.
      Eleven patients with innervation defects showed pathologic sphincter
      contractions. Anorectal manometry is a valuable tool to differentiate between
      innervation defects and constipation of other etiologies.

PMID- 9574421
TI  - [Prospective study of the transit time in intestinal neuronal abnormalities].
AB  - In a prospective study 106 children with intestinal neuronal malformations
      underwent intestinal transit-time studies. In only 50% of the children with
      intestinal neuronal dysplasia type B or immature ganglia was the transit time
      prolonged. On the contrary, hypoganglionosis and heterotopia of the submucous
      plexus led to severe transport disorders with subsequent bowel resection.

PMID- 9574422
TI  - [Surgical treatment of chronic pancreatitis in children].
AB  - Chronic relapsing pancreatitis and its hereditary form are very rare in children.
      Our experience with early operative treatment in nine children is presented. The
      good exocrine and endocrine function of the pancreas in these patients justifies
      early operation when typical changes of the pancreatic duct are present since it
      shortens the relapsing clinical course and maintains good function of the
      pancreas.

PMID- 9574423
TI  - [Diagnosis and surgical therapy of thyroid gland diseases in childhood].
AB  - Among children, thyroid disease rarely points to a particular surgical therapy
      and therefore requires a very specific surgical approach as well as close
      interdisciplinary cooperation between pediatricians, pediatric surgeons, and
      nuclear medicine practitioners, in particular regarding the follow-up. As a
      consequence, excellent functional and long-terms results can be achieved. The
      extent of the radical surgery pertaining to the small, encapsulated papillary
      carcinoma is still being discussed and investigated.

PMID- 9574424
TI  - [Pyogenic periproctitis infections in childhood].
AB  - A total of 128 pediatric pyogenic perianal infections were recorded prospectively
      in 1984-1995; over 70% arose in children below the age of 2 years. A quarter of
      all perianal abscesses developed a recurrence between 3 weeks and 3 years after
      the initial operation, while five children had an anal fistula after deroofing of
      anal abscesses. The early age of onset and frequent anomaly of anal crypts (12%)
      suggests a partly congenital etiology due to impaired fusion of the proctodaeal
      membrane or rudimentary anorectal duplications for both conditions.

PMID- 9574425
TI  - [Is primary would closure in septic pediatric surgery contraindicated?].
AB  - Since 1994, 25 children have been treated for abscesses of the soft issue. After
      the incision, a complete debridement was done, followed by implantation of a
      collagen sponge containing gentamicin and primary wound closure. Only two relapse
      were seen, which had to be re-opened.

PMID- 9574426
TI  - [Minimal invasive bypass operations on the beating heart and using mechanical
      stabilization of the heart surface].
AB  - Different minimally invasive techniques are currently being controversially
      discussed among cardiac surgeons. For revascularization of anterior myocardial
      vessels, off-bypass procedures were performed in 64 cases through an
      anterolateral submammary minithoracotomy using the left internal mammary artery.
      Application of mechanical epicardial stabilization facilitated adequate exposure
      of the anastomosis and resulted in good patency rates and a low number of
      complications.

PMID- 9574427
TI  - [Wound infections after heart surgery interventions--a cost analysis].
AB  - Decreasing financial resources in the health care system require effective cost
      management. For this reason and due to special modalities of reimbursement
      regulations for open heart procedures, we analyzed the extent of additional costs
      caused by subsequent deep wound infections requiring surgical revision. The real
      costs of 12 consecutive cases of sternal infections out of a total of 1,124 open
      heart procedures in 1996 were assessed and differentiated.

PMID- 9574428
TI  - [Surgical treatments of aortic dissection (Stanford type A) with retrograde
      cerebral circulation and deep hypothermia].

PMID- 9574429
TI  - [Surgical therapy of chronic atrial fibrillation with the "Cox/Maze-III
      operation"].
AB  - We examined the results of simultaneous surgical treatment of chronic atrial
      fibrillation using a Cox/Maze III operation during mitral valve surgery (n = 12),
      atrial secundum defect closure (n = 1), combined operation (mitral valve and
      atrial secundum; n = 1) and thrombectomy from the left atrium (n = 1). Mean
      preoperative atrial fibrillation was 5.1 years (range 0.5-12 years). In the mean
      follow-up period of 13.1 months (1-24 months), 14 patients (93%) had sinus
      rhythm. CONCLUSION: (1) The surgical treatment of chronic atrial fibrillation
      using a Cox/Maze III operation can be performed without increased perioperative
      or postoperative risks; (2) Cox/Maze III operation represents an effective
      surgical treatment of chronic atrial fibrillation.

PMID- 9574430
TI  - [Surgical treatment of acute infectious endocarditis].

PMID- 9574431
TI  - [Surgical treatment of acute endocarditis--which preoperative diagnosis does the
      surgeon need?].
AB  - In a group of 140 patients undergoing operation for acute infectious endocarditis
      in an 8-year period, the value of preoperative diagnostic procedures was analyzed
      in a retrospective study. Echocardiography was sufficient to establish the
      diagnosis in each case, angiography did not add any information about the
      endocarditis, but detected severe coronary heart disease in 19 patients.
      Abdominal sonography is mandatory to exclude intestinal foci, while CT scan of
      the brain only has to be performed in patients with neurologic deficits.

PMID- 9574432
TI  - [Monitoring growth factors during wound healing as the basic principle of
      effective clinical growth factor therapy?].
AB  - The microenvironment of healing human skin wounds is continuously monitored by a
      cutaneous chamber model. In recent studies in patients, baseline data for barrier
      function, temporal profiles of growth factors, and other mediators of healing
      were established. This model may be useful in clinical research of modulators of
      healing and wound pharmacology.

PMID- 9574433
TI  - [Analysis of cost measures in treatment of severely burned patients].
AB  - An analysis of costs and profit and an evaluation of the different cost
      parameters was performed in our burn centre, which treated 50-80 patients per
      year between 1991 and 1995. The cost-profit relationship (costs 3.7-4.6 million
      DM/year, profit 3.8-5.0 million DM/year) is balanced. The main cost parameters
      are staff costs (1.3-1.9 million DM/year), costs for medical treatment (1.5-1.8
      million DM/year), and costs for internal services (0.6-0.9 million DM/year).

PMID- 9574434
TI  - [Neovascularization of pre-formed tissue flaps in relation to arteriovenous blood
      flow of the implanted vascular pedicle. Experimental study in the rabbit].
AB  - In 45 Chinchilla-Bastard rabbits, a skeletonised arterio-venous pedicle was
      implanted on the subsurface of a 15 x 8 cm abdominal skinflap to create a
      neovascularised axial prefabricated flap. In order to evaluate the potency of
      neovascularisation in relation to the blood flow of the pedicle, we compared
      minimal blood flow by distal ligation (model 1) with maximal blood flow by distal
      microvascular arteriovenous shunt anastomoses (model 2) of the implanted vascular
      pedicle. The results show that 8 and 12 days after pedicle implantation, tissue
      flap perfusion in model 2 is significantly earlier and better in comparison to
      model 1.

PMID- 9574435
TI  - [Analysis of prolonged intensive care after abdominal surgery interventions with
      special reference to quality of life and economy].
AB  - In a retrospective study of 62 surgical patients with at least 30 days of
      intensive care, a hospital mortality rate of 40.3% with a median survival time of
      3.7 years for the discharged patients (n = 37) was found. The median
      gastrointestinal quality of life Index (GLQI) for the surviving patients was 104
      points, and overall 56 quality-adjusted life years (QALYs) were obtained,
      resulting in costs of 68,250 DM per QALY. Although intensive care is one of the
      most expensive treatment modalities in the health system, economic aspects should
      not be the cause for withdrawing or withholding intensive therapy.

PMID- 9574436
TI  - [Surgical interventions in extracorporeal membrane oxygenation (ECMO)].
AB  - Extracorporeal membrane oxygenation is a suitable technique for short-term
      treatment of resistant respiratory failure with a comparably low mortality rate
      of 32%. However, pulmonary complications are quite often encountered during ECMO
      therapy making thoracic interventions necessary. The most frequent of these
      complications is hemorrhage followed by lung fistula, which remain resistant to
      conventional therapy. The indication for operative lung resection during ECMO
      treatment must remain restricted to selected cases, since these procedures have a
      high morbidity.

PMID- 9574437
TI  - [Apache II score and prognosis of intensive care patients after trauma--results
      of a quality assurance study of 939 patients].
AB  - The APACHE II score is a well-known measure of illness severity and widely used
      for prognosis in the ICU. A total of 91 trauma patients were identified among 939
      ICU admissions (18 months), and their actual mortality (11/91; 12.1%) clearly
      exceeds the prognosis due to APACHE II (7.1%). Trauma-specific scores (TRISS,
      ISS, and RTS) revealed much higher estimates: 13%-22% which confirms a systematic
      underestimation of risk of death score in trauma patients in the APACHE system.

PMID- 9574438
TI  - [Electronic data processing of patient performance assessment and nursing care
      documentation on the surgical intensive care unit].
AB  - A software was created that picks up the attainments and procedures of a surgical
      intensive care unit on a computer to control and handle the processes and
      operations. After the data have been obtained, they are used for science and for
      the controlling department to establish what costs are incurred for a patient.

PMID- 9574439
TI  - [Effective costs of intensive care: TISS and TISS-28 for the evaluation of an
      intensive care unit].
AB  - In 1996, Miranda published the TISS-28, a simplified version of the well-known
      Therapeutic Intervention Scoring System (TISS) for the evaluation of intensive
      care. A prospective observational study in 939 patients compared both scores, and
      the TISS-28 was found to show less interobserver variation. A cost analysis based
      on 1995 data revealed a value of 68.70 DM per TISS-28 point, which can be used to
      calculate the average costs for groups of patients, e.g., 1410 DM for 1 day
      postoperative surveillance in the ICU.

PMID- 9574440
TI  - [Does rationing of intensive care beds lead to premature ward return with
      preventable complications?].
AB  - Readmission to the surgical intensive care unit was necessary in 105 of 2269
      patients (4.6%) who were discharged between 1991 and 1995. Mortality was 20%
      Cardiopulmonary reasons during the first 72 h after initial discharge were rare
      [33 patients (1.4%)].

PMID- 9574441
TI  - [The Munich intensive care transport system. Patient transport and intensive care
      conditions].
AB  - In November 1990 a new program for transporting critically ill patients by a 24-h
      specialized intensive care transportation system at the Munich Hospital
      Grosshadern was established. All medical equipment similar to that in the ICU
      allows invasive and non-invasive monitoring, drug administration, and a
      sophisticated respiratory therapy, provided by a Siemens Servo 300 ventilator.
      Even extracorporal lung augmentation (ECLA) and cardiac pump assistance by
      special mobile devices are possible during the transport.

PMID- 9574442
TI  - Role of the matrix in autosomal dominant polycystic kidney disease.
AB  - At present, even though we have accumulated a wealth of knowledge regarding
      structural, and molecular changes in ADPKD, the primary cause of the disease
      remains unknown. Obviously the gap in our understanding of the nature of the
      disease has been narrowed substantially over the past decade. With current
      techniques and efforts, the ultimate mystery of ADPKD should be resolved during
      the next decade.

PMID- 9574443
TI  - Megalin-mediated endocytosis in renal proximal tubule.
AB  - Megalin, a 600 kDa membrane protein belonging to the IDL receptor family is
      highly expressed in the endocytic pathway of renal proximal tubules. In addition,
      this receptor is found in several other epithelia facing transcellular fluids but
      is also expressed in the parathyroid glands. Recent studies have established this
      protein as probably the most important receptor for endocytosis of macromolecules
      filtered in the renal glomeruli. The ligands reported to bind to megalin consist
      of a variety of different substances including albumin, vitamin-carrier
      complexes, proteinases and proteinase-inhibitor complexes, lipoprotein particles,
      receptor associated protein (RAP), different drugs and calcium.

PMID- 9574444
TI  - Inter-regulated balance between gelatinases and tissue inhibitor (TIMP-1) in
      isolated human glomeruli.
AB  - Leukocyte infiltration inside glomeruli necessitates basement membrane collagen
      i.v. breakdown and leads to mesangiolysis, cell proliferation and extracellular
      matrix synthesis during the repair process as observed in the course of acute
      glomerulonephritis, vasculitis and acute graft rejection. Two matrix
      metalloproteinases, MMP-2 and MMP-9 gelatinases, are expressed and co-secreted in
      balance with the tissue inhibitor of metalloproteinases-1 (TIMP-1) by activated
      neutrophils as well as by glomerular cells and are aimed to control basement
      membrane collage i.v. deposition. Using a conventional double mesh sieving
      method, pure populations of glomeruli were isolated from fresh human cortex
      specimen and maintained in short-term cultures. ELISA, zymography and
      immunoblotting of conditioned serum-free media revealed glomerular MMP-2, MMP-9
      and TIMP-1 secretion and activity while reverse transcription-polymerase chain
      reaction amplification of cellular RNA demonstrated glomerular transcripts coding
      for these enzymes and their inhibitor. When purified neutrophils were allowed to
      adhere onto Transwell apparatus in contact with glomerular suspensions,
      neutrophil 92 kDa gelatinase seemed apparently inhibited mainly because the
      production of TIMP-1 was enhanced on both sides of the insert. Glomerular 72 kDa
      and 92 kDa gelatinases were activated shortly (1 to 6 h) after neutrophils had
      interacted with glomeruli and furthermore upon activation by inflammatory or
      vasoactive mediators such as phorbol. Decreased neutrophil MMP-9 activity
      together with reduced MMP-9 mRNA levels and protracted TIMP-1 transcription and
      secretion during cell-cell interaction could participate to cell detachment from
      degraded basement membranes and to increased collagen i.v. deposition leading to
      glomerulosclerosis after initial glomerular injury by inflammatory cells.

PMID- 9574445
TI  - Drug delivery to the kidneys and the bladder with the low molecular weight
      protein lysozyme.
AB  - The low molecular weight protein (LMWP) lysozyme is a suitable drug carrier for
      renal drug targeting. When the tubular reabsorption of a LMWP can be prevented,
      the protein will be excreted in the urine. In this way, lysozyme (LZM) conjugates
      might also be used as carriers for targeting to the urinary tract. Since positive
      domains on the protein surface are important for the interaction with the tubular
      uptake-receptor, we studied the urinary excretion of a drug-LZM conjugate with
      and without positive charge on the LMWP. We synthesized two conjugates with the
      fluorescent compound fluorescein. A positively charged conjugate was obtained by
      reacting fluorescein isothiocyanate (FITC) with LZM at a 1:1 molar to molar
      ratio; this conjugate contained six free primary aminogroups. The conjugate
      without positively charged groups was obtained by reacting the remaining free
      primary aminogroups of the FITC-LZM with succinic anhydride (Suc). The Suc-FITC
      LZM contained only 0.2 free primary aminogroups per molecule. We studied the
      pharmacokinetics of the conjugates in freely moving Wistar rats. The FITC-LZM
      conjugate was excreted intactly into the urine for 29 +/- 4% of the injected
      dose. The Suc-FITC-LZM was excreted into the urine intactly for 45 +/- 4%. These
      data indicate that the excretion of a drug-LMWP conjugate into the urine can be
      increased by decreasing the positive charge on the carrier surface. Such a
      carrier may be an attractive candidate for drug targeting to the bladder.

PMID- 9574446
TI  - Role of renal nerves in hemodynamic and natriuretic responses to saline in
      rabbits with impaired baroreflex sensitivity.
AB  - The hemodynamic and urinary Na+ excretory response to a 2.5-fold increase in NaCl
      by i.v. infusion were assessed in conscious male rabbits with either high (BShi,
      salt-insensitive) or low (BSlo, salt-sensitive) cardiac baroreflex sensitivity,
      before, and 11-14 days after bilateral renal denervation. Effective renal plasma
      flow (ERPF) and proximal tubular Na+ reabsorption were measured by para-amino
      hippurate (PAH) and Li+ clearances, respectively, before and after NaCl infused
      for 2 hr at a rate of 0.11 mL/kg/min. Intact BShi rabbits, showed a significant
      natriuresis within 30 min which was associated with an increase in ERPF and
      inhibition of proximal tubular reabsorption. The Na+ excretion rate was much
      slower in BSlo rabbits, while ERPF and proximal tubular reabsorption remained
      unchanged. Renal denervation reduced MAP, increased basal ERPF, Na+ and Li+
      excretion in both groups, and abolished the difference in the renal hemodynamic
      re-sponse and Li+ excretion to increased NaCl, but not that in the rate of Na+
      excretion. The data suggest that BSlo rabbits do not increase their ERPF and Li+
      in response to saline because of an inability to bring about an inhibition of
      renal sympathetic nerve activity. This could be due to an impairment in the
      sensitivity of their cardiopulmonary baroreceptors. The difference in the rate of
      natriuresis in the two groups of rabbits which remained after renal denervation
      could involve an additional hormonal or a local renal mechanism.

PMID- 9574447
TI  - Stimulation of mitogen activated protein kinase and cellular proliferation in
      renal proximal tubular cells.
AB  - We have studied activation of mitogen-activated protein kinase (MAP kinase) and
      [3H]-thymidine uptake as a marker for cellular proliferation in a proximal
      tubular cell line of the American Opossum kidney (OK cells). Adrenaline,
      serotonin, epidermal growth factor and insulin all stimulated MAP kinase and [3H]
      thymidine uptake. This stimulation of cellular proliferation was markedly reduced
      by an inhibitor of the MAP kinase pathway, PD 98059. Epidermal growth factor
      stimulated MAP kinase activity more effectively than the other agonists, but all
      four had similar effects on OK cellular proliferation. These data indicate that
      amine neurotransmitters may be of similar importance for tubular regeneration as
      classical growth factors.

PMID- 9574448
TI  - Basic fetoprotein in normal and pathologic urine.
AB  - We developed a latex agglutination nephelometric immunoassay for urinary basic
      fetoprotein (BFP) that functioned well and had good specificity, precision, and
      recovery. Reference intervals started below 0.5 microgram/L, the lower limit of
      the range of sensitivity of the assay, and went up to 7.0 micrograms/L at the
      97.5th percentile without age- or sex-related variation, in accordance with the
      NCCLS guidelines. BFP was unstable at pH 5.0 at 4 degrees C and 25 degrees C. The
      western blot method showed BFP found in the semen to be structurally identical to
      purified BFP from hepatoma ascites, in which concentration ranged from 94.2 to
      145.2 micrograms/L and, further, to have the same molecular weight and reactivity
      with a monoclonal antibody. BFP levels were elevated in cases urinary BFP
      concentration included ureter stone, infection, and prostate and bladder cancer.
      Moreover, BFP concentration correlated closely with that of alpha 2
      macroglobulin, indicating that BFP is probably secreted locally in close
      pathophysiologic association with post-renal hemorrhage. We thus conclude that
      BFP is a urinary nonspecific marker for inflammation or tumor. The best
      indication for BFP as a tumor marker may be follow-up when diagnosis of
      genitourinary cancer is definite.

PMID- 9574449
TI  - Which urinary proteins are decreased after angiotensin converting--enzyme
      inhibition?
AB  - It is believed that angiotensin converting-enzyme (ACE) inhibitors lower
      proteinuria by acting on glomerular hemodynamics. This hypothesis predicts that
      the urinary excretion of a tubular protein should be unaffected by ACE
      inhibition. In the present study we have compared the excretion of albumin and
      Tamm-Horsfall Glycoprotein (THGP), a protein secreted only by renal tubules,
      before and after ACE inhibition. Urinary protein excretion was measured with the
      Phast System, a method based on SDS polyacrylamide gel electrophoresis followed
      by silver staining, in 15 essential hypertensives, after at least 4 weeks of wash
      out from any drug and after 2 months of ACE inhibition with oral Quinapril. After
      2 months of ACE inhibition, blood pressure (BP), body weight, urinary output,
      heart rate, plasma glucose, plasma and urinary creatinine, urate and
      electrolytes, and creatinine clearance, were not different from baseline values.
      Plasma ACE activity decreased from 76 +/- 7 to 10 +/- 4 U/mL (mean +/- SEM, 2
      tails paired t test, p = 0.0001). Both albumin and THP urinary excretions
      decreased from 51 +/- 6 to 43 +/- 4 mg/ 24 h (p = 0.05) and from 19 +/- 3 to 12
      +/- 1 mg/24 h (p = 0.02), respectively. This unexpected result suggests that ACE
      inhibitors may act also at the level of renal tubular cells.

PMID- 9574450
TI  - Can continuous intraperitoneal infusion of 125I-iothalamate and 131I-hippuran be
      used for measurement of GFR in conscious rats?
AB  - We previously described a method to measure GFR in conscious spontaneously
      voiding rats. This method circumvents the need for anesthesia and for bladder
      instrumentation. It's main principle is the correction of renal 125I-iothalamate
      clearance for incomplete urine collection by the ratio of plasma and renal
      clearance of co-infused 131I-Hippuran. A disadvantage of this technique is the
      requirement of an intra-arterial catheter for infusion of the renal function
      tracers. We therefore tested whether intraperitoneal infusion of 125I-iothalamate
      and 131I-Hippuran can be used for such a GFR measurement in conscious
      spontaneously voiding rats. We found that during intraperitoneal administration,
      stable plasma levels of 131I-Hippuran could be obtained. However, urinary
      recovery of 131I-Hippuran was incomplete (66 +/- 32%), leading to a significant
      overestimation of GFR by 140 +/- 13% in comparison with the GFR measured by the
      intra-arterial technique. Thus intraperitoneal infusion of renal function tracers
      cannot replace intra-arterial infusion.

PMID- 9574451
TI  - A reappraisal of the bladder cumulative method as a reliable technique for the
      measurement of glomerular filtration rate.
AB  - In order to quantify the decline in renal function, repeated measurements of GFR
      are necessary. The conventional procedure is cumbersome and time expending so
      that alternative clearance techniques are needed. We propose a simple isotopic
      technique for measuring GFR by 99mTc-DTPA and external counting of the bladder by
      gamma camera (bladder cumulative method). This consists in the measurement by
      external counting of the amount of labelled filtration marker accumulated in the
      bladder after intravenous bolus injection. In 36 adult patients with all degrees
      of renal impairment (serum creatinine 0.9-9.3 mg/dL) GFR was measured twice, once
      by the conventional method (continuous i.v. infusion of the filtration marker and
      urine collection by spontaneous voiding) and once by the bladder cumulative
      method. 99mTc DTPA was used in performing both methods. A satisfactory agreement
      was found between GFR measured by bladder cumulative method (BCM) and by
      conventional method (CM). The BCM averaged 60.0 +/- 36.7 mL/min and the CM +/- SD
      averaged 62.8 +/- 36.6 mL/mm. The ratio BCM/CM +/- SD was 0.95 +/- 0.14 (y =
      0.94x + 1.14; r = 0.94). Considering the 17 patients with renal insufficiency
      (GFR < 60 mL/min) an even better agreement between the two methods was found. In
      these patients the BCM averaged 28.4 +/- 17.2 mL/min; the CM averaged 29.1 +/-
      16.6 mL/min; and the ratio BCM/CM was 0.96 +/- 0.08 (y = 1.03x - 1.47; r = 0.99).
      The day-to-day variability of BCM, studied in another 11 patients, was lower than
      that of creatinine clearance (variation coefficient for duplicate measurements:
      7.18 +/- 6.65 SD for BCM, 15.68 +/- 8.80 SD for CM, p < 0.01). The bladder
      cumulative method is a simple procedure for the accurate measurement of GFR, in
      particular in patients with renal insufficiency. It represents a reliable tool
      for estimating the decline in renal function.

PMID- 9574452
TI  - Estimation of glomerular filtration rate by sinistrin clearance using various
      approaches.
AB  - Two protocols for the determination of glomerular filtration rate (GFR) from
      sinistrin clearance are considered: a bolus injection and a bolus followed by
      infusion. On both occasions, serial blood and urine samplings are scheduled up to
      6 h. Four calculation methods are compared for estimating GFR from the data
      obtained during each protocol: classical UV/P (ratio of urinary excretion rate
      over plasma concentration) after bolus or bolus plus infusion; 2-point (log
      linear slope multiplied by apparent volume of distribution); D/AUC (ratio of dose
      over area under the curve) after bolus; and Rin/P (ratio of infusion rate over
      steady-state concentration) during infusion. Some refinements of the calculations
      are devised. Data are simulated by running a bicompartmental pharmacokinetic
      model with renal elimination, and contaminating the values with an array of
      random errors. The statistical performance of the respective calculation methods
      is assessed by graphical means. The UV/P method performs poorly during 2 hours
      following the bolus; on both bolus and infusion data, it suffers from imprecision
      on the urinary volume. The 2-point method is acceptable between 1 and 4 h after
      bolus; later, the estimates become much less precise. The D/AUC method appears
      highly reliable when integrating the concentrations up to 3 h after bolus; it
      requires extrapolation towards infinity. The Rin/P method is satisfactory if
      applied later than 3 to 4 h after the loading dose. The advantages and drawbacks
      of each methods must be evaluated in relation with the particular clinical
      setting in which GFR is to be estimated. D/AUC represents the most advisable
      approach for snapshot renal testing in subjects or patients without important
      renal impairment.

PMID- 9574453
TI  - Iohexol plasma clearance in determining glomerular filtration rate in diabetic
      patients.
AB  - The plasma clearance of iohexol has recently been proposed as a new method for
      estimating GFR. The iohexol plasma clearance was compared with that of 51Cr-EDTA
      in 32 diabetic patients (12 IDDM, 20 NIDDM; age 23-70; diabetes duration 1-35
      years) with normal to impaired renal function (serum creatinine: 0.8-6.4 mg/dL).
      Bolus i.v. injection of 51Cr-EDTA (1 muCi/kg) was followed by 5 mL slow i.v.
      injection of Omnipaque (Nycomed, Oslo, Norway). Samples for radioactivity and
      iohexol analysis were drawn at 0, 5, 10, 15, 30, 60, 90, 120, 150, 180, 210, 240,
      270, 300 min (+360 and 420 min if serum creatinine > 2.0; +1440 min if > 5.0
      mg/dL). Iohexol was assayed in duplicate by HPLC throughout a Nova-Pak C18 column
      (Waters-Millipore, USA). Only the second peak obtained during elution of iohexol
      (about 4.5 min) was used for calculation. Dilution tests show highly linear
      regressions for concentrations between 3.25-650 micrograms/mL (r = 0.99).
      Imprecision of iohexol assay (the whole procedure from deproteinization to
      chromatography) was: intra-assay 1.4 +/- 1.5%, mlsd (95% CI: 1.0-1.8%); inter
      assay 3.0 +/- 2.7% (1.4-4.6%). Iohexol plasma clearance ranged between 12.9 and
      150.9 mL/min, while 51Cr-EDTA plasma clearance between 11.9 and 149.8 mL/min with
      excellent correlation (iohexol = 0.95 51Cr-EDTA + 2.49; r = O.995). Mean CV
      between the two methods was 1.7% (range 0-4.9%) with a significant negative
      correlation (r = 0.5 I, p = 0.007) with the GFR levels. Correlation between
      repeated measurements, performed in eight patients, was excellent (r = O.994, P =
      0.0001). In diabetes, GFR measured by plasma clearance of iohexol shows an
      excellent agreement with plasma clearance of 51Cr-EDTA throughout a wide range of
      renal function. Iohexol provides an accurate alternative method for measuring
      GFR.

PMID- 9574454
TI  - Creatinine clearance can be predicted from plasma creatinine and body composition
      analysis by means of electrical bioimpedance.
AB  - The aim of this study was to evaluate the possibility of predicting creatinine
      clearance (CCr) from plasma creatinine (PCr) and body com-position analysis by
      means of electrical impedance, thereby avoiding urine collection. Fat-free mass
      (FFM) and body cell mass (BCM) were measured in 50 renal patients (M29, F21; aged
      17-74 years; mean 52.6) with different degrees of renal function (PCr 0.8-9.0
      mg/dL, mean 2.13) by using a tetrapolar impedance plethysmograph. The
      relationship between 24 h-urinary creatinine excretion (UCr) and FFM and BCM was
      evaluated in 20 of the above reported patients (MI I, F9; PCr 0.8-9.0 mg/dL, mean
      2.27). The mean ratio of 24 h UCr/FFM was 25.6 mg/kg in males and 22.5 in females
      and that of 24 h UCr/BCM was 51.9 mg/kg in males and 48.1 in females. CCr was
      estimated in the remaining 30 patients (M18, F12; PCr 0.9-8.8 mg/dL, mean 2.04)
      from individual FFM and BCM values and PCr. In the same patients CCr was
      predicted also according to the Cockcroft and Gault formula and, for comparison,
      was measured with the conventional method by collecting 24 h urine, CCr predicted
      from the values of FFM and BCM gave a good estimate of 24 h CCr, more precise
      than that of Cockcroft and Gault CCR. Also, the repeatability of the predicted
      CCr was clearly better than that of 24 h CCr. In conclusion, creatinine clearance
      can be predicted, avoiding urine collection, from plasma creatinine and body
      composition analysis by means of electrical impedance.

PMID- 9574455
TI  - Serum levels of tumor associated trypsin inhibitor (TATI) and glomerular
      filtration rate.
AB  - TATI (tumor associated trypsin inhibitor) is a low molecular weight protein
      employed as a tumor marker. To evaluate the role of the kidney in the clearance
      of TATI, we studied the rat kidney uptake of 125I-TATI. Total body scan
      demonstrated a high radioactivity in the kidneys of the rats and none in other
      organs. The relationship between serum TATI and glomerular filtration rate (GFR)
      was studied in man. For comparison serum beta 2-microglobulin (beta 2M) arid
      plasma creatinine were also determined. The decrease in GFR was accompanied by an
      increase in the other parameters. Serum TATI increased in patients with renal
      failure (GFR < 20 mL/min) 12.4 times with respect to subjects with normal renal
      function (p < 0.001, non-parametric Mann-Whitney test), beta 2M increased 7.6
      times (p < 0.001) and creatinine 4.7 times (p < 0.001). The increase in TATI is
      statistically significant already in patients with GFR 60-40 mL/min (p < 0.005).
      These results suggest that TATI is handled by the kidney. It is a sensitive
      marker of reduction in renal function.

PMID- 9574456
TI  - Is serum cystatin C a sensitive marker of glomerular filtration rate (GFR)? A
      preliminary study on renal transplant patients.
AB  - Human cystatin C is a basic low molecular mass protein (13,359 Dalton) freely
      filtered through the glomerulus and almost completely re-absorbed and catabolized
      by proximal tubular cells. We measured serum cystatin C in 38 kidney transplant
      patients (23 males, 15 females) aged between 6 and 32 years. To assess renal
      function, serum and urinary creatinine were also determined in all patients, and
      creatinine clearance was finally calculated. Cystatin C was determined by a
      particle-enhanced turbidimetric assay, and creatinine was measured by gas
      chromatography-mass spectrometry. To compare the diagnostic efficiency of
      cystatin C with that of creatinine, inulin clearance was performed on 12 renal
      transplant patients, and receiver operating characteristic (ROC) analysis was
      applied. The results of this study demonstrate that serum cystatin C
      significantly increases in renal transplant patients with reduced creatinine
      clearance (< 70 mL/min per 1.73 m2) and that the diagnostic accuracy of serum
      cystatin C is better than of serum creatinine. Cystatin C may be utilized as a
      very marker of reduced GFR.

PMID- 9574457
TI  - Specific determination of PAH and its N-acetyl metabolite by HPLC increases the
      accuracy and precision of PAH clearance measurements.
AB  - PAH (N-(4-aminobenzoyl)-glycin) clearance measurements have been used for 50
      years in clinical research for the determination of renal plasma flow. The
      quantitation of PAH in plasma or urine is generally performed by colorimetric
      method after diazotation reaction. Although straightforward, the measurements
      must be corrected for the nonspecific residual response observed in blank plasma.
      We have therefore developed an HPLC method for the specific determination of PAH
      and its metabolite NAc-PAH using a gradient elution ion-pair reverse-phase
      chromatography with UV detection. The Nacetyltransferase (NAT-1 or NAT-2
      dependent) activity does not seem clinically relevant nor does it affect notably
      PAH clearances, although NAc-PAH represents 10.2 +/- 2.7% of the PAH excreted
      unchanged in 12 healthy subjects. The performance of the HPLC technique has been
      compared with the colorimetric method using urine and plasma samples collected
      from 12 healthy volunteers following a priming dose of PAH followed by a constant
      rate infusion. Good correlations (r = 0.94 and 0.97, for plasma and urine
      respectively) are found between the results obtained with both techniques.
      However, the colorimetric method gives higher concentrations of PAH in urine
      while the concentrations in plasma are lower than those determined by HPLC.
      Hence, both renal (CLR = U x V/P) and systemic (CLS = Rinf/Css) clearances are
      systematically higher (35.1%, resp. 17.8%) with the colorimetric method. The
      fraction of PAH excreted by the kidney CLR/CLS calculated from HPLC data (n =
      143) is, as expected, always < 1 (mean = 0.73 +/- 0.11), whereas the colorimetric
      method gives a mean extraction ratio of 0.87 +/- 0.13 implying unphysio-logical
      values (> 1) in some cases. In conclusion HPLC not only enables the simultaneous
      quantitation of PAH and NAc-PAH, but may also provide more accurate and precise
      PAH clearance measurements.

PMID- 9574458
TI  - Gamma-glutamyltransferase is a reliable marker for tubular effects of contrast
      media.
AB  - The aim of this study was to evaluate the usefulness of the measurement of
      urinary excretion of the brush-border enzyme gamma glutamyl-transferase (GGT), in
      comparison with that of alanine aminopeptidase (AAP), as a marker for tubular
      toxicity due to contrast media (CM). Urinary activities of AAP and GGT were
      measured prior to the administration of CM and 1, 3 and 5 days after in forty
      nine adult renal patients undergoing a radiological examination with
      intravascular administration of CM. The behavior of GGT was similar to that of
      AAP. In fact, urinary activities of both AAP and GGT increased greatly after CM.
      This effect was maximal on the 1st day and statistically significant for both
      enzymes. Furthermore, on the 1st day a relevant increase of enzyme activity (at
      least +50% over the basal value) was observed in the same number of patients
      (67%) for AAP and GGT. The concordance between GGT and AAP variations was high
      and statistically significant. Finally, different variables (osmolarity, dose of
      CM, and baseline renal function of the patients) had a similar effect on urinary
      excretion of AAP and GGT. The repeatability of duplicated determinations of GGT
      resulted better than that of AAP. In conclusion, the good concordance of the
      results of GGT with those of AAP justifies the use of GGT as a marker for tubular
      effects due to CM. Furthermore, the measurement of GGT has a better repeatability
      than that of AAP.

PMID- 9574459
TI  - Urinary excretion rates of multiple renal indicators after kidney
      transplantation: clinical significance for early graft outcome.
AB  - Post-reperfusion inflammation as well as anti-allograft response occur following
      kidney transplantation. We evaluated tissue damage by multiple renal indicators
      and searched for rejection predictors forewarning serum creatinine upturns.
      Twenty recipients (43 +/- 9 y; donors' age 35 +/- 16 y) of first renal grafts
      were studied. All through their hospital stay (35 +/- 18 d, range 17-75 d) we
      measured serum levels of urea, creatinine and electrolytes along with urinary
      excretion rates of total protein, albumin, enzymes (GGT, NAG, AAP) and
      electrolytes. During the period of observation, peaks were seen on the 1st day
      for serum creatinine, serum K+ and urine albumin output; on the 2nd day for urine
      Na+, GGT, AAP and protein excretion rates; on the 4th day for urea and creatinine
      outputs; on the 5th day for NAG output. On the 14th day, serum urea and
      creatinine as well as urine GGT, NAG, AAP, albumin and total protein were still
      elevated compared to 20 healthy control subjects. Delayed/slow graft function was
      observed in six recipients with higher pre-transplantation plasma lipids and
      lower donor HDL cholesterol. Hospital stay time was correlated with need for post
      transplantation dialysis (p = 0.01) and recipient proteinuria by time 0 (TO) to
      day 3 (p = 0.02). Cold ischemia time was positively associated with 0-3 d serum
      creatinine, 0-3 d urinary urea and protein outputs (multiple r 0.9, p < 0.001).
      Multivariate analysis of longitudinal data showed that recipients' serum
      creatinine was positively correlated (p < 0.001) with urine AAP and negatively
      correlated with urine albumin, with diuresis volume and urine creatinine (p <
      0.01). Serum creatinine elevations were preceded (previous 1-7 d) by increases in
      urinary indicators, the probability being higher in the presence of multiple
      simultaneous abnormalities. Useful parameters predictive of favorable graft
      outcome prior to transplantation included a brief cold ischemia time and a normal
      donor/recipient serum lipoprotein profile. Following transplantation, useful
      parameters were a high diuresis volume at time zero along with low urine NAG and
      high albumin outputs; early (first opst-graft 3 d) polyuria, low urea and GGT,
      high K, NAG and total protein excretions.

PMID- 9574460
TI  - Growth factors in metanephric development.
AB  - During embryonic life, renal morphogenesis is characterized by a defined period
      of intense cellular activity, inductive-transformation of undifferentiated cells
      to polarized epithelia, in-growth of capillaries into an intricate parenchymal
      epithelial-mesenchymal mass, and finally the maturation into an organ with
      diverse structural and biological functions. It should be emphasized that the
      interactions between various growth factors and their receptors, FCM
      glycoproteins and proto-oncogenes are required for proper epithelial: mesenchymal
      interactions essential to the process of nephrogenesis. A balance between the
      activities of these macromolecules, whether essential or redundant, is needed to
      orchestrate the proper cell signals and responses to assure the progression of
      normal organogenesis. Finally, in spite of the enormous wealth of data in the
      literature, the process of renal development is so complex that a clear picture
      has yet to emerge of the precise coordinated and sequential events that result in
      the formation of a mature functioning kidney.

PMID- 9574461
TI  - The insulin-like growth factor-I axis in acute renal failure.
AB  - We have examined the response of the renal insulin-like growth factor (IGF-I)
      axis to acute ischemic injury in the rat Key findings included a decrease in IGF
      I mRNA and peptide levels, a decrease in GH receptor gene plus protein expression
      and a decrease in the IGF binding proteins except for IGF binding protein I.
      Administration of GH to compensate for the reduced GH receptor binding corrected
      the IGF-I mRNA levels suggesting a relative GH deficiency. Interestingly, IGF-I
      receptor mRNA levels were unchanged while plasma membrane IGF-I receptor number
      increased two fold. This appeared to be due to a redistribution of receptors to a
      membrane location. IGF-I receptor autophosphorylation and tyrosine kinase
      activity were intact despite severe uremia for up to 6 days. We propose that this
      increase of functional IGF-I receptors following acute tubular necrosis will
      sensitize the kidney to the administration of exogenous IGF-I.

PMID- 9574462
TI  - Insulin-like growth factor-I treatment to enhance renal function in advanced
      chronic renal failure.
AB  - Because of the potential for IGF-I to enhance renal function in advanced chronic
      renal failure (CRF) we set out to determine whether IGF-I can induce a sustained
      increase in renal function in patients with near end-stage renal failure. To this
      end we first examined the impact of CRF on the pharmacokinetics of IGF-I and then
      we examined the effect of prolonged IGF-I treatment on the renal function of
      patients with an average GFR of 17 mL/min/1.73 m2. Interestingly the metabolic
      clearance rate of IGF-I in CRF subjects was similar to that in normal subjects
      even though the total serum IGF-I levels rose to higher maximum levels. This
      increase was due to a reduced volume of IGF-I distribution, a consequence of the
      elevated serum IGF binding proteins in CRF subjects. Treatment with IGF-I (60
      mg/kg twice daily sc) for 31 days resulted in a 14% and 18% increase in the
      inulin and PAH clearances respectively (n = 6 patients). These parameters
      returned to basal levels on stopping treatment. Serum immunoreactive IGFBP-3
      levels fell and IGFBP-2 and -3 levels rose during IGF-I therapy. Adverse effects
      were mild, of short duration and easily manageable. Thus IGF-I pharmacokinetics
      are largely unchanged in CRF and the administration of IGF-I produces a modest
      improvement in the GFR. These results appear to justify more extensive
      examination of the therapeutic role of IGF-I in the treatment of CRF.

PMID- 9574463
TI  - Circulating levels of IGF-I in patients with chronic uremia on conservative
      dietary treatment.
AB  - The assessment of nutritional status is a very important step in the clinical
      management of chronic uremic patients, because of the influences of chronic renal
      failure and of dietary manipulations on the energy and protein metabolism. In
      this study some serum biochemical markers of protein nutrition, including IGF-I
      and pre-albumin, have been measured in chronic renal failure patients treated
      with two different low-protein diets, according to the residual renal function
      for several months. Our results showed no significant changes of IGF-I, pre
      albumin or albumin serum levels in the patients treated with a very low-protein
      diet (0.3 g/Kg b.w. per day) supplemented with essential amino acids and
      ketoacids, in comparison with the patients on a conventional low-protein (0.6
      g/Kg b.w. per day) diet.

PMID- 9574464
TI  - Intracellular processing of transforming growth factor-beta in mesangial cells.
AB  - Transforming growth factor beta 1 (TGF-beta 1) is a multifunctional regulator of
      cell-growth, differentiation and extracellular matrix formation in several
      physiological conditions. It plays a crucial role in the process of
      glomerulosclerosis. Mature TGF-beta 1 is secreted as a latent form associated
      with the latency associated peptide (LAP), and its activation occurs through the
      LAP cleavage. The intracellular localization and the mechanisms of activation of
      TGF-beta 1 protein have not been elucidated in the mesangial cell. In the present
      report we examined the intracellular processing from TGF-beta 1 precursor to the
      latent-TGF-beta 1 in cultured mesangial cells by immunocytochemistry, using three
      rabbit polyclonal antibodies directed against different epitopes of human TGF
      beta 1. The anti-LAP-TGF-beta 1 precursor Ab stained mesangial cells in the
      perinuclear region and in the cytoplasm in the area corresponding to the rough
      endoplasmic reticulum; the anti-COOH-terminal fragment of TGF-beta 1 Ab reacted
      in the same area, in vesicular structures located in the cytoplasm and
      furthermore, in the mesangial cell clusters, so-called hillocks, with an
      extracellular pattern; the anti-NH2-terminal fragment of TGF-beta 1 Ab stained
      only large exocytotic vesicles at the periphery of the cytoplasma. Our
      investigations suggest a conformational rearrangement of pro-TGF-beta 1 molecule
      occurring between the rough endoplasmic reticulum and the TGF-beta 1 secretion
      and support the idea that in mesangial cells the activation of TGF-beta 1 occurs
      during the secretion process. In conclusion, the processing of TGF-beta 1 in
      mesangial cells seems to be similar to that one observed in other mesenchymal
      cells.

PMID- 9574465
TI  - Oral sodium bicarbonate reduces proximal renal tubular peptide catabolism,
      ammoniogenesis, and tubular damage in renal patients.
AB  - Oral sodium bicarbonate (NaHCO3) is widely used to treat acidosis in patients
      with renal failure. However, no data are available in man on the effects on
      proximal renal tubular protein catabolism or markers of tubular injury. We have
      developed methods to allow such studies, and both increased tubular catabolism of
      99mTc-labelled aprotinin (Apr*), as well as tubular damage were found in
      association with increased ammonia (NH3) excretion in patients with nephrotic
      range proteinuria. We now examine the effects of reducing renal ammoniogenesis,
      without altering proteinuria, using oral NaHCO3 in 11 patients with mild/moderate
      renal impairment and proteinuria. Renal tubular catabolism of Apr* was measured
      before and after NaHCO3 by renal imaging (Kidney uptake, K% of dose) and urinary
      excretion of free 99mTcO4- (metabolism, Met% of dose/h) over 26 h. Fractional
      degradation (Frac) was calculated from Met/K (/h). Fresh urine was also analyzed
      for NH3 excretion every fortnight from 6/52 before treatment. Total urinary N
      acetyl-beta-D-glucose-aminidase (NAG) and the more tubulo-specific NAG "A2" were
      measured. 51CrEDTA clearance and 99mTc-MAG 3 TER were also assessed. After NaHCO3
      Met over 26 h was significantly reduced (from 1.3 +/- 0.2% of dose/h to 0.9 +/-
      0.1% dose/hr, p < 0.005), as was Frac of Apr* (from 0.06 +/- .006/h to 0.04 +/-
      0.005/hr, p < 0.003). NH3 excretion also fell significantly (from 0.9 +/- 0.2
      mmol/h to 0.2 +/- 0.05 mmol/h, p < 0.007), as did both total urinary NAG (from
      169 mumol/24 h, 74-642 mumol/24 h to 79 mumol/ 24 h, 37-393 mumol/24 h, p <
      0.01), and the NAG 'A2' isoenzyme (from 81.5 mumol/24 h, 20-472 mumol/24 h to
      35.0 mumol/24 h, 6-388 mumol/24 h, p < 0.001). Proteinuria remained unaltered,
      and there was no change in blood pressure nor in glomerular haemodynamics. Oral
      NaHCO3 may thus pro-tect the proximal renal tubule and help delay renal disease
      progression.

PMID- 9574466
TI  - Patterns of dietary intake and serum lipids interact with proteinuria as risk
      factors for progression of chronic renal failure.
AB  - This prospective study assessed the interactions between patterns of nutrient
      intake and serum lipids with other risk factors for progression of chronic renal
      failure. The study cohort consisted of 52 individuals with documented chronic
      renal failure, 18 women and 34 men, with a mean age of 65 +/- 11 years at the
      time of recruitment. The dependent variable was the rate of progression of
      chronic renal failure, which was determined by the slope of the curve generated
      from five or more values of the reciprocal of serum creatinine (SCr-1) and
      divided by time (in months of follow-up) for each patient, and recorded in
      dung/month. The independent variables included dietary factors (phosphorus,
      protein); serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol,
      triglycerides); proteinuria; serum phosphorus; serum albumin; serum glucose; and
      blood pressure. Serum creatinine was drawn in a fasting state and determined
      using the picric acid technique on five or more occasions for each patient. The
      mean monthly rate of decline in dL/mg/month was calculated for each patient. The
      cohort was followed for 1.5 years. Descriptive statistics were determined for all
      variables. Analysis of principal components was used to generate variables
      representing patterns of nutrient intake and serum lipids. The outcome variable
      was modeled using stepwise linear regression which included principal components
      representing dietary and serum lipid patterns. The Student's t test and the F
      test were used for hypothesis testing. All tests were significant at p < 0.05.
      RESULTS AND CONCLUSIONS: Multicolinearity prevented the inclusion of more than
      one individual dietary or serum lipid variable into the multiple linear
      regression model of rate of decline in kidney function. Principal components
      representing patterns of dietary intake and serum lipids, contributed to the
      prediction of rate of decline in renal function together with proteinuria.

PMID- 9574468
TI  - Source of reactive oxygen species in anti-Thy1 nephritis.
AB  - In proliferative glomerulonephritis, both macrophages and mesangial cells
      generate reactive oxygen species (ROS), contributing to the development of
      glomerular injury. We have attempted to determine which cell produces ROS during
      anti-Thy1 nephritis (ATN) in rats. The generation of ROS was studied using
      luminol amplified chemiluminescence (GCL) on isolated glomeruli.
      Immunohistochemical studies used avidin-biotin complex (ABC) to label macrophages
      and mesangial cells. Immediately after ATN induction, mesangiolysis and
      infiltration with ED-1 positive cells (referred to as macrophage) was noted with
      a peak at day 1. After day 4, mesangial proliferation appeared with a decrease of
      the ED-1 positive cells and a prominent increase of PCNA positive cells (regarded
      as mesangial cells). In the early phase of ATN, GCL, reflecting ROS generation,
      increased along with the appearance of ED-1 positive cells. GCL subsequently
      decreased as mesangial cells increased. This suggested that macrophage were the
      principal participants in ROS generation in the early phase of ATN although
      mesangial cells cannot be completely disregarded in the generation of ROS and
      development of glomerular injury.

PMID- 9574467
TI  - Role of dyslipidemia in the progression of chronic renal disease.
AB  - The connection between lipids and the rate of progression of chronic renal
      disease was retrospectively examined in 70 patients who were divided into 2
      groups according to their baseline creatinine clearance (CCr): Group 1 (Gp1)
      contained 30 patients with CCr 60-40 mL/min followed for 40.0 +/- 13.3 months;
      Group 2 (G2) contained 40 patients with CCr 39-15 mL/min followed for 39.0 +/-
      18.2 months. The following parameters were considered: basal and final CCr
      proteinuria per unit of CCr (UProt/CCr); the difference between final and basal
      UProt/CCr (delta UProt/CCr); the change in CCr/month (delta CCr); baseline
      triglycerides (TG), total (TC), HDL (HDLC) and LDL (LDLC) cholesterol, Apo AI,
      Apo B, Lp(a). Besides in basal CCr the 2 groups significantly differed in the
      final CCr, final UProt/CCr, delta UProt/CCr, delta CCr. No differences were
      observed concerning lipid parameters except for Lp(a) (G1 14.8 +/- 13.6, G2 28.7
      +/- 27.4 mg/dL; p < 0.05). Baseline TG (G1 184.1 +/- 61.3, G2 187.5 +/- 72.1
      mg/dL) and Apo B (only G2 1.05 +/- 0.32 g/L) were significantly higher than
      normal subjects and the Apo AI/Apo B ratio (G1 1.42 +/- 0.43, G2 1.33 +/- 0.45)
      were significantly lower than in normal subjects. delta CCr, while inversely
      correlated in both groups with delta UProt/CCr (p < 0.01), only in G2 did it
      correlate directly with the Apo AI/Apo B ratio (p < 0.05) and inversely with Apo
      B and LDLC (p < 0.05). Although a correlation between Lp(a) and delta CCr was not
      found, 20/22 patients (3/5 G1, 17/17 G2) with a level > 30 mg% ran a progressive
      course. A natural progression of CRI, heralded by an increasing UProt, is highly
      frequent when baseline CCr is < 40 mL/min; only then lipids seem to add a burden
      to the renal damage.

PMID- 9574469
TI  - Genetic control of susceptibility for renal damage in hypertensive fawn-hooded
      rats.

PMID- 9574470
TI  - Detection of mature macrophages in urinary sediments: clinical significance in
      predicting progressive renal disease.
AB  - The ability to predict the rate of progression of renal parenchymal disease may
      help in its clinical management. We undertook characterization of urinary
      macrophages obtained from patients with various renal diseases paying special
      attention to the differentiation from non-progressive to progressive renal
      diseases. A total of 84 patients were divided into one of three categories. A
      highly progressive group included patients with rapidly progressive
      glomerulonephritis, diabetic nephropathy, membranoproliferative
      glomerulonephropathy, primary focal segmental sclerosis and diffuse proliferative
      lupus nephropathy, moderately progressive group included those with IgA
      nephropathy and Alport's syndrome and non-progressive group included patients
      with thin basement membrane nephropathy, minimal change nephrotic syndrome,
      idiopathic renal hematuria and urolithiasis. Urinary sediments were reacted with
      four monoclonal antibodies (CD68/macrophages vimentin, cytokeratin, and
      25F9/mature macrophages). In normal individuals mature macrophages (25F9+ cells)
      were absent in urinary sediments. The number of 25F9+ cells in the urine was
      highest in the highly progressive group, less prominent in the moderately
      progressive group, and virtually absent in the non-progressive group. The 25F9+
      cells reacted with anti-CD68 and antivimentin antibody, whereas the 25F9+ cells
      did not react with anti-cytokeratin antibody. These findings indicate that the
      detection of mature macrophages in urine is useful to estimate the prognosis of
      renal parenchymal diseases and may help to differentiate some glomerular diseases
      (e.g., thin basement membrane disease vs. Alport's syndrome, and minimal change
      nephrotic syndrome vs. primary focal segmental sclerosis).

PMID- 9574471
TI  - Bone mass and breast cancer in postmenopausal women.

PMID- 9574472
TI  - Combinations of second-line drugs for rheumatoid arthritis: is remission
      induction a reasonable goal?

PMID- 9574473
TI  - The expression and localization of Scl-70/DNA topoisomerase I vary throughout the
      cell cycle.
AB  - PURPOSE AND METHODS: We investigated the expression and localization of
      topoisomerase I by Western blot and indirect fluorescent antibody assay,
      respectively, using anti-Scl-70/topo I from patients with diffuse scleroderma.
      The contribution of topoisomerase I to DNA replication was assessed using cells
      treated with the topoisomerase I inhibitor camptothecin. RESULTS: Scl-topo I was
      detected at all cell cycle phases as a single immunoreactive band of 100 kDa.
      Extracts from cells in the S phase contained the largest amount of immunoreactive
      Scl-70/topo I. Variations in the subcellular distribution of Scl-70/topo I were
      seen throughout the cell cycle, with a speckled nucleoplasmic distribution during
      G1 contrasting with concentration within the nucleolus during S. Camptothecin
      exposure blocked topoisomerase I expression and caused a significant decrease in
      DNA production. CONCLUSION: These data suggest (1) that topomerase I is active
      mainly during the S phase and contributes to DNA replication, and (2) that
      topoisomerase I may be involved in ribosomal gene transcription.

PMID- 9574474
TI  - Is spa therapy cost-effective in rheumatic disorders?
AB  - OBJECTIVE: To evaluate the cost-effectiveness of spa therapy for rheumatic
      diseases and sequelae of bone and joint injuries. PATIENTS AND METHODS: A
      prospective randomized, case-control design was used with health care cost
      reimbursements during the year before and after spa therapy as the measure of
      efficacy. Spa therapy is reimbursed by the national health insurance system in
      France, subject to prior agreement. The 220 patients who filed applications for
      spa therapy with the national health insurance payment center for northern France
      during the first half of 1994 were included in the study. Seventy-two patients
      met national health insurance system criteria for spa therapy (Group 1), the
      remaining 148 patients were assigned at random to spa therapy (Group 2, n = 74)
      or no spa therapy (Group 3, n = 74). This method allowed us to avoid selection
      bias during recruitment of our control group. RESULTS: Perceived morbidity was
      evaluated based on health care utilization, expressed as numbers of health care
      investigations or procedures and as days of medication use in mean recommended
      dosages. Health care cost reimbursements by the national health insurance system
      failed to decrease during the year after spa therapy, and increased in those
      patients who had already received spa therapy on one or more occasions. Only in
      the first-ever spa patients were decreases in health care utilization in the area
      of rheumatology seen during the year after spa therapy; the largest decreases
      were for use of nonsteroidal antiinflammatory drugs (from 49 to 26 days) and
      muscle relaxants. No differences in health care utilization were found in
      patients who had received spa therapy on at least one other occasion. Also, when
      criteria for spa therapy were not met, no differences in health care utilization
      were found between patients who did and did not receive spa therapy. CONCLUSION:
      These data suggest that current national health insurance policies regarding the
      reimbursement of spa therapy need to be reevaluated.

PMID- 9574475
TI  - Iliopsoas bursopathies. A review of twelve cases.
AB  - Synovial cysts are far less common at the hip than at the knee and usually occur
      in patients whose hip cavity communicates with the iliopsoas bursa. We report 12
      cases of enlargement of the iliopsoas bursa, nine men and three women, with a
      mean age of 48 years. The six patients with septic bursitis had severe symptoms
      similar to those seen in septic arthritis of the hip. Chronic pain with or
      without a palpable inguinal swelling was the main symptom in the six remaining
      patients, some of whom had compression of neighboring structures making the
      diagnosis more difficult. Ultrasonography is the best first-line investigation in
      patients with an inguinal swelling. Computed arthrotomography with examination of
      the synovial fluid or magnetic resonance imaging should be performed as a
      confirmatory diagnostic test. Our series provides evidence of the efficacy of
      appropriate antimicrobial therapy in septic cases and of corticosteroid
      injections into the bursa or hip cavity in nonseptic cases.

PMID- 9574476
TI  - Computed tomography in primary glenohumeral osteoarthritis without humeral head
      elevation.
AB  - Few studies have evaluated computed tomography in glenohumeral osteoarthritis
      without humeral head elevation. Two recent studies included only ten and 11
      patients, respectively. We evaluated computed tomography findings in 113 cases of
      primary glenohumeral osteoarthritis without humeral head elevation. Glenoid
      retroversion was substantially increased, with a mean of 16 degrees versus 8
      degrees in a control group. The method used to measure this parameter was
      reproducible, with a mean interobserver variability of 4 degrees for a 95%
      confidence interval (P < or = 0.05). Humeral retrotorsion was apparently
      decreased (8 degrees), but osteoarthritis-related changes in the humeral head
      resulted in substantial measurement errors (interobserver variability, 11 degrees
      for a 95% confidence interval; P < or = 0.05). Humeral head subluxation was found
      in 35% of cases and measurement of this parameter was reproducible (interobserver
      variability, 4 degrees for a 95% confidence interval). Changes in the glenoid
      over time were dependent on the position of the humeral head in the glenoid
      fossa, which classified the shape of the glenoid with satisfactory
      reproducibility (intra- and interobserver Kappa, 0.68). The subscapularis and
      infraspinatus muscles were normal (stage 0 or 1) in 98% and 91% of cases,
      respectively and the method of Goutallier and Bernageau used for muscle
      evaluation proved highly reproducible (Kappa, 0.85). Computed tomography is
      invaluable for planning surgical treatment for primary glenohumeral
      osteoarthritis without humeral head elevation.

PMID- 9574477
TI  - Short-term evaluation of periradicular corticosteroid injections in the treatment
      of lumbar radiculopathy associated with disc disease.
AB  - OBJECTIVES: The purpose of this study was to evaluate the feasibility and
      efficacy of periradicular corticosteroid injections performed under fluoroscopic
      guidance in the treatment of pain originating in the lumbosacral nerve roots.
      METHOD: Forty patients presenting with lumbosciatica or femoral neuralgia
      unresponsive to conventional conservative treatment were admitted to the study.
      Patients with nerve root pain due to infectious, tumorous or inflammatory
      diseases were excluded, as were patients who needed immediate surgery. Pain was
      evaluated using a visual analog scale on the day of the injection and ten (D10)
      and ninety (D90) days later. RESULTS: All patients were evaluated as scheduled on
      D10 and D90. The mean visual analog scale score decreased from 53.3 mm at
      baseline to 30.1 mm on D10 and to 21.8 mm on D90. Ninety per cent of patients had
      a visual analog pain score decrease on D10 and 85% on D90. Reported side effects
      were two cases of mild spontaneously regressive acne and one case of radicular
      pain exacerbation of less than one day's duration. CONCLUSION: Periradicular
      injections of corticosteroids done under fluoroscopic guidance as an outpatient
      procedure was effective and safe in our study and may deserve to be used as part
      of the conservative management of lumbar nerve root pain before resorting to more
      invasive methods.

PMID- 9574478
TI  - From polycystic bone angiomatosis to Gorham's disease. Two case-reports and
      literature review.

PMID- 9574479
TI  - Can an osteoporotic vertebral fracture cause compression of the spinal cord or
      cauda equina.
AB  - A 78-year-old woman developed an osteoporotic fracture of L2 followed two months
      later by spinal cord compression. Imaging study findings suggested a malignancy
      but a biopsy showed osteonecrosis, of which there was no evidence on the imaging
      studies. Osteonecrosis may be the cause of neurologic compromise associated with
      osteoporotic vertebral fractures.

PMID- 9574480
TI  - Two new cancer locations accompanied with palmar fasciitis and polyarthritis.
AB  - Only 35 cases of cancer with palmar fasciitis and polyarthritis have been
      published to date. We report two new cases, one with a transitional cell
      carcinoma of the renal pelvis and the other with an adenocarcinoma of the uterus.
      Neither of these locations has been reported in association with palmar fasciitis
      and polyarthritis. Palmar fasciitis with polyarthritis can occur in a wide range
      of cancers and warrants extensive investigations for a malignant tumor.

PMID- 9574481
TI  - Spontaneous infective osteitis pubis in a young woman.

PMID- 9574482
TI  - Anatomic basis for the treatment of aneurysms of the upper cervical segment of
      the internal carotid artery by extra-intracranial cervico-petrous bypass with
      inverted "in situ" saphenous vein graft.
AB  - In the surgical treatment of aneurysms of the upper cervical portion of the
      internal carotid a., exclusion of the affected vascular segment combined with an
      extra-anatomic cervico-petrous bypass using a vein graft (great saphenous v.) may
      be considered. One of the problems specific to these extra-anatomic bypasses is
      associated with the sub-cutaneous positioning of the vein graft, exposing it to
      risks of angulation, torsion or extrinsic compression that may lead to early
      venous thrombosis. We suggest an alternative technique using the principle of
      telescoping and consisting of positioning the vein graft within the cervical
      portion of the artery ("in situ" bypass). The cervical portion of the ICA may be
      used as a tunnel for the vein graft since there are no collateral arterial
      branches at this level. The technical features of such a bypass are defined by
      means of an anatomo-surgical study in the cadaver: exposure of the petrous
      portion of the internal carotid a. in its horizontal segment by subtemporal
      access, exposure of the ICA in the neck, transverse arteriotomies of the ICA,
      angioplasty with a Fogarty balloon, intracarotid telescoping of a saphenous vein
      graft from the cervical to the petrous region, distal end-to-end anastomosis
      between the vein graft and the petrous portion of the ICA, and proximal end-to
      end anastomosis between the vein graft and the cervical portion of the ICA.

PMID- 9574483
TI  - The oculomotor nuclear complex in humans. Microanatomy and clinical significance.
AB  - This study has been performed to define better the anatomical structure of the
      oculomotor nuclear complex and its neuronal components. The oculomotor nuclear
      complex was examined in fixed and serially sectioned midbrains from 12 adult
      subjects free from neurological diseases. The complex included the somatic
      portion, (formed by multipolar motor neurons), and the parasympathetic portion,
      (formed by oval or fusiform preganglionic cells), on each side of the median
      raphe. The somatic portion consisted of the lateral somatic cell column and the
      caudal central nucleus. The somatic column measured from 0.2 x 0.1 mm to 3.4 x
      1.4 mm (X = 2.4 x 1.2 mm) in transverse section. It was divided into the
      principal, intrafascicular and extrafascicular parts. The principal part was
      subdivided into the dorsal, intermediate and ventral portions. Isolated
      multipolar neurons were also found in the periaqueductal gray matter, the
      interstitial nucleus of Cajal, the Edinger-Westphal nucleus and the fibre bundles
      of the oculomotor nerve. These cells most likely represent the displaced motor
      neurons of the oculomotor nerve. The caudal central nucleus was 0.8 x 0.6 mm in
      size. The Edinger-Westphal nucleus consisted of the rostral, ventral and dorsal
      parts; the longest rostrocaudal diameter of this nucleus measured 7.1 mm. The
      anatomical data of our study are relevant clinically and allow explanation of the
      neurologic signs following complete or partial lesions of the oculomotor nuclear
      complex.

PMID- 9574484
TI  - The membranous part of the human interventricular cardiac septum.
AB  - The arrangement of collagen and elastic fibers of the membranous part of the
      interventricular septum (PMS) was studied in hearts from adult humans. Connective
      bundles formed a network of fairly independent tendons arranged in two layers.
      The tendinous bundles consisted essentially of type I collagen fibers while type
      III fibers were visible as a thin network with transversely and longitudinally
      oriented meshes around the muscle bundles. Cranial and caudal to the PMS were
      narrow and irregular bands of collagen fibers that apparently represented zones
      of low resistance to the high blood pressures acting from the left to the right
      heart chambers. The predominance of fiber bundles arranged in an approximately
      transverse direction with regard to the arterial cone axis suggests a resistance
      to enlargement resulting from high aortic blood pressure. Elastic fibers were
      observed in the transitional zone between the cardiac muscle and the PMS. They
      were continuous with elaunin fibers and these with oxytalan fibers closely
      intermingled with the narrow network of type I collagen fibers of the PMS. The
      successive transformation of elastic fibers, which were very numerous in the
      muscle-tendon transition, into elaunin and these into oxytalan fibers toward the
      central portions of the PMS suggests a functional sequence characterized by a
      high elasticity and consequent mobility of the transition region itself and by a
      progressive increase of resistance in this portion.

PMID- 9574485
TI  - Anatomy of the intramural venous sinuses of the right atrium and their
      tributaries.
AB  - A precise knowledge of the mode of opening of the vv. on the anterior wall of the
      right ventricle, i.e., directly or by means of intramural venous sinuses in the
      right atrium, is of fundamental importance for cardiologic methods of examination
      and treatment. We dissected 32 hearts obtained from cadavers belonging to adult
      individuals of unknown age and sex, fixed and stored in formalin. A total of 151
      veins were detected for the 32 cases. The following distribution was observed: 33
      right marginal vv. (m) in 29/32, 59 anterior vv. of the right ventricle (a) in
      29/32, 29 vv. of the arterial cone (c) in 26/32, 17 posterior vv. of the cone (p)
      in 17/32, and 13 Zuckerkandl vv. (z) in 13/32. Of these veins, a) 4 m emptied
      into the right atrium, with one of them forming a bifurcation and emptying twice;
      b) 4 m continued into a small cardiac v.; c) 6 collector vv. present in 4/32
      cases emptied into the right atrium and received 2 m, 5 a, 2 c, 3 p and 2 z; d)
      35 intramural venous sinuses were present in 30/32 or 94% of cases emptied into
      the right atrium and received 15 m, 26 a, 5 c, 4 p, 3 z and 32 collector vv.,
      into which 8 m, 28 a, 22 c, 10 p and 8 z drained. In conclusion, these venous
      sinuses are normal and are very important for venous drainage.

PMID- 9574486
TI  - The recurrent laryngeal nerve (RLN): application to transhiatal oesophagectomy.
AB  - To emphasize the risks of recurrent laryngeal nerve lesions during transhiatal
      oesophagectomy an anatomical study of the course of the recurrent laryngeal nerve
      (RLN) was performed. Twenty RLN were dissected in their thoracic portion. This
      work showed the constancy of the low origin of the nerve in the adult under the
      aortic arch, and its course in the tracheal angle. It confirmed the close
      connections of the nerve with the posterior mediastinal viscera. Lastly, it
      displayed oesophageal nerve branches arising from the RLN and a few anastomoses
      between them and the tracheal nerve branches. This anatomical disposition
      resulted into the difficulty of transhiatal oesophaphagectomies and the risk of
      injury of the recurrent laryngeal nerve. The possibility of nerve lesions can
      explain the respiratory complications of this surgical approach.

PMID- 9574487
TI  - Arterial and lymphatic supply of the knee integuments.
AB  - The surgical approach to the anterior knee region carries a risk for
      postoperative integument infection and skin necrosis. A hypothesis is that
      surgical approach may damage integumental blood supply and additionally the
      lymphatic drainage from the foot and leg. The goal of this study was to describe
      the arteries and lymphatics directly affected by the antero-medial approach.
      Injection of the femoral a. was used to identify the femoral and popliteal aa.
      and their branches distributed to the integument of the anterior, medial and
      lateral aspects of the knee. Lymphatic injection into the plantar aspect of the
      first toe was also performed to identify the subdermal lymphatics traversing the
      area. Our results showed that most of the blood supply arises from the medial
      aspect of the knee integuments. However, subcutaneous arterial anastomoses
      provide a significant blood-supply when there is interruption of the medial
      vessels as seen in the medial surgical approach to the knee. Most of the
      lymphatic drainage originating from the foot crosses the knee region on the
      medial side, opposite or below the tibial tuberosity. Because the subdermal
      arterial network is well-developed, the medial approach for knee surgery does not
      endanger the anterior knee integuments as long as the lateral vascular supply is
      preserved. However, this approach may interrupt the lymphatic circulation,
      particularly in the case of an extended incision, which could explain
      postoperative edema and an increased rate of wound infection.

PMID- 9574488
TI  - Anatomic and functional aspects of the kinetics of the shoulder joint capsule and
      the subacromial bursa.
AB  - This anatomic study was devoted to the kinetics of the shoulder joint and
      especially the subacromial region. Following dissection of the shoulder joint
      capsule and subacromial region of 80 unpreserved shoulder joints, the anatomic
      relationships of the subacromial space in the neutral position and in continuous
      abduction (30 degrees, 60 degrees and 90 degrees with fixed scapulae) were
      examined. These investigations were supplemented by histologic preparations. In
      the course of our examinations we discovered a gliding mechanism of the
      subacromial bursa. Moreover, we found a subcoracoid attachment of the shoulder
      joint capsule and a precoracoid ligamentous connection running between the short
      head of the biceps brachii m. and the coracoacromial ligament. We termed this the
      coracoid aponeurosis, which facilitates gliding behaviour of the shoulder joint
      capsule beneath the coracoid process. In view of this gliding mechanism of the
      subacromial bursa and the coracoid aponeurosis, discovered in the course of our
      investigations, we have to reassess the kinetics of the sub-acromial and
      subcoracoid space. Further, we should reconsider our operative technique in cases
      of the subacromial or subcoracoid impingement syndrome.

PMID- 9574489
TI  - Microsurgical anatomy of the internal vertebral venous plexuses.
AB  - Few studies have been done about the venous vascularization of the spine since
      neuroradiologic studies in the 1960s and 70s. The aim of this study was to
      clarify the topography of the internal vertebral venous plexuses in relation to
      the posterior longitudinal ligament and the dura. The relationships of the vv.
      were studied at different levels of the spine. The internal vertebral venous
      system of seven cadavers was injected with a blue bicomponent silicon rubber. It
      consisted with an anterior and a posterior venous plexus. At the cervical level,
      the anterior longitudinal vv. are located in a dehiscence of the periosteal
      layer, in the lateral part of the spinal canal. At each level, they joined the
      contralateral one at the midline by a retrocorporeal v. located behind the
      posterior longitudinal ligament. No vv. were found in the epidural space. There
      was a major development of the retrocorporeal v. of the axis, but it did not
      receive any venous drainage from the vertebral body. At the thoracic and lumbar
      levels, the anterior venous plexuses remain within a dehiscence of the periosteal
      layer, which is thinner. The retrocorporeal vv. become pre-ligamentous. We did
      not find any posterior venous plexuses at the cervical level, but they were
      evident at the thoracic level and became more voluminous and sinusoidal in the
      lumbar region.

PMID- 9574490
TI  - Kinetic magnetic resonance imaging analysis of swallowing: a new approach to
      pharyngeal function.
AB  - The emergence of turbo-FLASH MR sequences allows us to acquire five 10-mm
      sections each second and thus to catch images of the soft tissues during
      function. One can trace the pathway of a liquid between the tongue, the soft
      palate, the epiglottis and the pharyngeal apparatus and analysis the role of the
      anatomic structures during swallowing. Restricted to the sagittal plane for the
      purpose of this preliminary study, this technique can be extended to the other
      planes to provide a three-dimensional analysis of oropharyngeal function or
      dysfunction.

PMID- 9574491
TI  - Assessment of the superior labrum of the shoulder joint with CT-arthrography and
      MR-arthrography: correlation with anatomical dissection.
AB  - The ability to detect and categorize SLAP (Superior Labrum Anterior to Posterior)
      lesions of the scapular labrum is of practical importance to the orthopedic
      surgeon and the radiologist. The aim of this study, performed on cadaveric
      shoulders, was to determine whether CT arthrography or MR arthrography is able to
      show normal anatomical variation of the glenoid labrum and detect labral
      abnormalities. CT arthrography, MR arthrography followed by anatomical dissection
      were performed on twenty three fresh frozen cadaveric shoulders and analysed by a
      radiologist and two orthopaedic surgeons. As Gadolinium intra-articular injection
      is not allowed in France, we used an iodinated contrast media for both MR
      arthrography and CT arthrography. In this study, the sensitivity of MR
      arthrography seemed higher than CT arthrography (respectively 4 and 3 labral
      lesions diagnosed out of five), although no significant statistical conclusions
      can be made due to the small number of cases. In conclusion, under such specific
      conditions, MR arthrography seems to be the method of choice for the detection
      and classification of labral lesions.

PMID- 9574492
TI  - Effect of normal ageing on the sites of aortic bifurcation and inferior vena cava
      confluence: a CT study.
AB  - The object of this retrospective study was to determine the sites of abdominal
      aortic bifurcation and inferior vena cava confluence in relation to age and sex.
      The study group comprised 180 subjects (90 males and 90 females) divided into 9
      groups by age (in decades). The positions of the aortic bifurcation and the
      inferior vena cava confluence were evaluated by CT, and linear regression models
      were fitted to the data. The positions of the aortic bifurcation and venous
      confluence showed a highly significant downward shift with increasing age (p =
      0.0001). The shift was more pronounced in women. The mean site of the aortic
      bifurcation for the whole group was at lower L4 (range, upper L3 to upper S1); in
      males, it was at upper L4 (range, upper L3 to upper L5), and in females at lower
      L4 (range, upper L3 to upper S1). The mean site of the venous confluence for the
      whole group was at disc L4-L5 (range, lower L3 to upper S1); in males, it was at
      disc L4-L5 (range, upper L4 to disc L5-S1), and in females at disc L4-L5 (range,
      lower L3 to upper S1). Thus, the aorta and the inferior vena cava can extend as
      low as the level of S1. These data are of relevance in laparoscopic procedures,
      especially in laparoscopic lumbar discectomy.

PMID- 9574493
TI  - Unusual origin of the ophthalmic artery and occlusion of the central retinal
      artery.
AB  - Any variations in the origin of the ophthalmic a. are uncommon and well-explained
      by the comparative anatomy and human embryology. A unique case is reported of an
      ophthalmic a. arising from the middle meningeal a. associated with an occlusion
      of the central retinal a. Embryologic variations which can give such an unusual
      origin are discussed. Although this association may be fortuitous, we consider
      that an unusual origin of the ophthalmic a. could be a further factor for an
      occlusion of the central retinal a.

PMID- 9574494
TI  - Anomalous insertional slip of latissimus dorsi muscle: arcus axillaris.
AB  - An anomalous muscular slip arising from the latissimus dorsi m. was encountered
      on the right side of a male cadaver during a dissection in our laboratory. The
      slip left the muscular part of the latissimus dorsi 8 cm distal to its insertion,
      coursed superolaterally anterior to the neurovascular structures and was inserted
      into the coracobrachialis fascia. The morphology of the additional slip and its
      possible clinical implications are discussed.

PMID- 9574495
TI  - HIV/AIDS prevention through community psychology.

PMID- 9574496
TI  - Factors influencing condom use among African American women: implications for
      risk reduction interventions.
AB  - Examined factors associated with condom use in a community-based sample of 423
      sexually active African American women. Measures were selected to reflect the
      components in prevailing models of health behavior. Condom users were higher on
      AIDS health priority, prevention attitudes, stage of change, behavioral
      intentions, reported more frequent and comfortable sexual communication with
      partners, perceived greater partner and peer approval for condom use, and
      reported that peers also used condoms. Women in exclusive relationships evidenced
      earlier stage of change, lower intentions to use condoms, fewer peers who engaged
      in preventive behaviors, perceived themselves to have lower risk, and had lower
      rates of condom use, higher education, and family income. Women in fluid
      relationships were at particularly high risk, with lower rates of condom use
      relative to women not in a relationship and greater sexual risk for HIV.
      Implications for HIV-risk reduction interventions with African American women are
      discussed.

PMID- 9574497
TI  - Partner influences and gender-related factors associated with noncondom use among
      young adult African American women.
AB  - We examined the partner influences and gender-related correlates of noncondom use
      among African American women. The prevalence of noncondom use was 45.3%. Women
      whose sexual partners were noncondom users were four times more likely to believe
      that asking their partner to use a condom implied he was unfaithful, three times
      as likely to have a partner who resisted using condoms, three times more likely
      to receive AFDC, twice as likely to be sexually nonassertive, three times more
      likely to believe that it was not difficult to find an "eligible" African
      American man, and three times as likely to have had one sexual partner. HIV
      prevention tailored towards African American women should address these partner
      influences and gender-related factors.

PMID- 9574498
TI  - Self-efficacy to use condoms in unmarried Latino adults.
AB  - Measures of self-efficacy to use condoms can clarify the barriers to condom use
      Latinos encounter. A 20-item scale, that differed slightly for men and women, and
      was based on extensive elicitation interviews, was used in a random digit dial
      household survey of 1,600 unmarried Latino adults in 10 states with large Latino
      populations. Self-efficacy was related to condom use for both men and women.
      Factor analyses revealed five correlated factors: Regular Partner, Impulse
      Control, Partner Resistance, STD Thoughts, and Condom Discussion. Both men and
      women reported lowest self-efficacy for impulse control and using condoms with a
      regular partner. Less-educated men and women had lower self-efficacy to discuss
      condoms, to manage partner resistance, to use condoms with a regular partner, and
      to control impulses, but there were few other demographic differences in self
      efficacy. The scale can be helpful in the design and evaluation of HIV
      prevention.

PMID- 9574499
TI  - Timing of HIV interventions on reductions in sexual risk among adolescents.
AB  - Examined the effectiveness of an HIV intervention program among 151 adolescents
      ages 13 to 24 years who were randomly assigned to (a) seven sessions of 1.5 hr
      each (10.5 hr); (b) three sessions of 3.5 hr each (10.5 hr); or (c) a no
      intervention condition. Using cognitive-behavioral intervention strategies,
      social skills and HIV-related beliefs, perceptions, and norms were targeted in
      both the three- and seven-session, small-group intervention conditions.
      Regression analysis indicated that over 3 months, the number of unprotected risk
      acts and the number of sexual partners were lower in the seven-session condition
      compared to the other conditions. Factors mediating risk acts changed in a
      complex manner. For example, perceived vulnerability increased for those with
      initially lower vulnerability scores among youths in the seven-session condition
      compared to others. Self-approval of condom use was also higher for those with
      initially low scores in the seven-session compared to the three-session
      condition. Self-efficacy for risk avoidance and condom use was significantly
      higher in the three-session condition for those with initially low scores
      compared to other groups. On the role-play measure, those with higher baseline
      scores in the low-pressure situation improved significantly only in the three
      session intervention; in the high-pressure situation, the participants reported
      significantly higher scores in the seven-session intervention, and those with
      higher scores improved the most. Results suggest the importance of multisession
      HIV intervention programs to be delivered with fidelity in community settings.

PMID- 9574500
TI  - HIV prevention with male prostitutes and patrons of hustler bars: replication of
      an HIV preventive intervention.
AB  - The core objectives of this study were to document the process by which a
      community-based organization replicated and adapted an experimentally developed
      intervention to its own use and to explore the effectiveness of that HIV
      prevention program for male prostitutes and other patrons in New York City
      "hustler" bars. The intervention model employed was based on previous research
      with gay men (Kelly, St. Lawrence, Diaz, et al., 1991; Kelly, St. Lawrence,
      Stevenson, et al., 1992) and inspired by diffusion of innovation theory (Rogers,
      1995). The effects of the current intervention were assessed on a sample of 1,741
      male prostitutes and bar patrons. Analyses indicated significant reductions in
      paid, unprotected sexual intercourse and oral sex following the intervention.
      Analyses further indicated that the data were partially consistent with the
      program's model, which specified that norms were the putative mediator of
      behavior change in the intervention. Also, the intervention's effects varied by
      bar and by participants' race/ethnicity. Data support the utility of the
      intervention model for an urban sample of men at high risk for HIV infection. The
      importance of exploring the mechanisms that underlie the intervention is
      discussed.

PMID- 9574501
TI  - Ecology, community, and AIDS prevention.
AB  - I explore the role that may be played by an ecological view of AIDS prevention
      and AIDS-related social concerns. The study of AIDS risk behavior and
      interventions designed to prevent AIDS have challenged Health Psychology's
      typically individualistic perspective. Issues of empowerment, psychological sense
      of community, interpersonal ties, resources, and culture are central to an
      understanding of risky sexual behavior and helping people to guard themselves
      from the threat of AIDS. However, despite Community Psychology's historical
      expertise in these areas, the field has only recently become involved in AIDS
      prevention efforts. I outline how resource-based, ecological theories may prove
      more helpful in addressing the AIDS pandemic than the individual, cognitive
      theories that have typically been adopted. Sexual behavior and associated risk
      are tied not simply to people's personal behavior and thoughts but to the
      likelihood of disease exposure in their ethnic group, the power and choices
      associated with power in that group, and the alternative means available of
      meeting their overall sexual, romantic, economic, and social goals. As such, AIDS
      research and intervention must simultaneously address the individual, social, and
      cultural spheres if insights that can translate to meaningful change can be
      expected to occur.

PMID- 9574502
TI  - A T-DNA from the Agrobacterium tumefaciens limited-host-range strain AB2/73
      contains a single oncogene.
AB  - Agrobacterium tumefaciens strain AB2/73 isolated from Lippia canescens has been
      described as a limited-host-range strain. Its tumor-inducing (Ti) plasmid has
      been found to lack DNA homology to known T-DNAs (L. Unger, S. F. Ziegler, G. A.
      Huffman, V. C. Knauf, R. Peet, L. W. Moore, M. P. Gordon, and E. W. Nester. J.
      Bacteriol. 164:723-730, 1985). We have isolated a T-DNA from AB2/73 by using a
      heterologous border sequence as a probe. The AB2/73 T-DNA sequence (3,504 bp) is
      flanked by canonical border sequences, has no detectable DNA homology with other
      T-DNAs, and contains only two genes: lsn (Lippia strain nopaline synthaselike
      gene) and lso (Lippia strain oncogene). The lso gene induces nondifferentiating
      tumors on a limited number of hosts when transferred by a Ti plasmid from a wide
      host-range strain. Part of the predicted Lso protein is weakly homologous to
      other Agrobacterium oncoproteins encoded by rolB, rolB, orf13, gene e, gene 5,
      and gene 3'. A 28-kb fragment corresponding to the virA to virE region was cloned
      by using a heterologous vir fragment as probe. The AB2/73 vir region is
      homologous to most of the C58 virulence region; however, the virA gene is most
      related to the virA gene of the Agrobacterium vitis limited-host-range strain
      Ag162.

PMID- 9574504
TI  - Identification of novel putative regulatory genes induced during alfalfa nodule
      development with a cold-plaque screening procedure.
AB  - Until now very few plant genes with possible regulatory functions during nodule
      development have been isolated. We have used a modified cold-plaque screening
      method to identify new transcripts expressed at low levels that are induced
      during nodulation. Several clones were isolated and characterized by their mRNA
      expression patterns during nodule development and in spontaneous nodules.
      Sequence homology with known genes of other organisms indicated that transcripts
      corresponded to (i) "basic" genes probably required during the growth of the
      nodule organ (e.g., structural proteins), (ii) genes related to the metabolic
      adaptations taking place during nodule morphogenesis and function (e.g., carbonic
      anhydrase), and (iii) genes containing regulatory motifs and/or homologies (three
      clones out of the 20 identified). The latter genes encode a zinc-finger
      containing protein, a putative protein kinase, and a Wilm's tumor (WT) suppressor
      homologue, respectively. Expression of the kinase and WT suppressor homologues
      was induced early in nodulation, although the latter was activated transiently.
      Accumulation of the Zn-finger gene transcripts was detected at a later stage of
      development and seems to be regulated in a complex manner. Hence, using a cold
      plaque screening procedure, we could identify genes that may play regulatory
      roles in the signal transduction pathways activated during nodule development.

PMID- 9574507
TI  - Symbiosis-specific expression of two Medicago truncatula nodulin genes, MtN1 and
      MtN13, encoding products homologous to plant defense proteins.
AB  - Two Medicago truncatula nodulin genes putatively encoding proteins structurally
      related to two classes of proteins commonly associated with plant defense
      reactions have been characterized. MtN1 is homologous to two small, cysteine
      rich, pathogen-inducible proteins from pea (pI39 and pI230), whereas MtN13 is
      closely related to the PR10 family of pathogenesis-related proteins. We show that
      neither MtN1 nor MtN13 is induced in leaves in response to pathogenic bacteria,
      and that both are exclusively expressed during nodulation. In situ hybridization
      experiments as well as Northern (RNA) studies of interactions between M.
      truncatula and either wild-type Rhizobium meliloti or mutants deficient in
      infection establish that MtN1 is associated with the infection process, while
      MtN13 represents the first specific marker described for the nodule outer cortex.
      Possible roles for MtN1 and MtN13 are discussed. We also present the
      identification of another member of the PR10 family, designated as MtPR10-1,
      whose regulation is strikingly different from that observed for MtN13, being
      constitutively expressed in roots and pathogen-inducible in leaves.

PMID- 9574508
TI  - Magnaporthe grisea pathogenicity genes obtained through insertional mutagenesis.
AB  - We have initiated a mutational analysis of pathogenicity in the rice blast
      fungus, Magnaporthe grisea, in which hygromycin-resistant transformants, most
      generated by restriction enzyme-mediated integration (REMI), were screened for
      the ability to infect plants. A rapid primary infection assay facilitated
      screening of 5,538 transformants. Twenty-seven mutants were obtained that showed
      a reproducible pathogenicity defect, and 18 of these contained mutations that
      cosegregated with the hygromycin resistance marker. Analysis of eight mutants has
      resulted in the cloning of seven PTH genes that play a role in pathogenicity on
      barley, weeping lovegrass, and rice. Two independent mutants identified the same
      gene, PTH2, suggesting nonrandom insertion of the transforming DNA. These first 7
      cloned PTH genes are described.

PMID- 9574509
TI  - A race-specific insertion of transposable element IS801 in Pseudomonas syringae
      pv. phaseolicola.
AB  - The isolation and cloning of a random amplified polymorphic DNA-polymerase chain
      reaction (RAPD-PCR) band specific for Pseudomonas syringae pv. phaseolicola race
      1 allowed us to design a pair of primers that amplify 1.2-kb race 1-specific and
      2.7-kb race 2-specific fragments, providing a rapid method for the identification
      of races by standard PCR methods. Restriction analysis revealed identical
      endonuclease sites in both fragments but the race 2 fragment contains a 1.5-kb
      insertion, identified as transposable element IS801 by sequence comparison. One
      complete and one partial open reading frame (ORF), each with a high probability
      of encoding a protein, have been identified in the 1.2-kb fragment common to both
      race 1 and race 2 sequences. As IS801 disrupts the partial ORF in the race 2
      fragment, the complete sequence of this ORF has been obtained as well as its
      promoter region. The possibility that it may encode an avirulence gene is
      discussed as well as the role of transposable elements in pathogen evolution.

PMID- 9574510
TI  - The presence and characterization of a virF gene on Agrobacterium vitis Ti
      plasmids.
AB  - Octopine and nopaline strains of Agrobacterium tumefaciens differ in their
      ability to induce tumors on Nicotiana glauca. The presence of a virF locus on the
      octopine Ti plasmid makes N. glauca a host plant for these strains, indicating
      that the VirF protein is a host-range determinant. Here we show the presence of a
      virF locus not only on the Agrobacterium vitis octopine/cucumopine plasmids
      pTiAg57 and pTiTm4, but also on the nopaline Ti plasmids pTiAT1, pTiAT66a, and
      pTiAT66b. On the octopine Ti plasmids from A. tumefaciens the virF gene is
      located between the virE locus and the left border of the T-region. In contrast,
      the virF gene on Ti plasmids of A. vitis is located at the very left end of the
      vir-region near the virA locus. The virF gene of pTiAg57 has been sequenced and
      codes for a protein of 202 amino acids with a molecular mass of 22,280 Da.
      Comparison showed that the virF gene from A. vitis strain Ag57 is almost
      identical to that from A. tumefaciens octopine strains. The transcription of the
      pTiAg57 virF is inducible by the plant phenolic compound acetosyringone through
      the presence of a vir-box consensus sequence in its promoter region. The VirF
      protein from pTiAg57 can complement octopine A. tumefaciens strains deleted for
      virF as shown by tumor formation on N. glauca.

PMID- 9574511
TI  - Mice defective in Fas are highly susceptible to Leishmania major infection
      despite elevated IL-12 synthesis, strong Th1 responses, and enhanced nitric oxide
      production.
AB  - MRL/MP-lpr/lpr (MRL/lpr) mice have a single mutation (lpr) of the fas apoptosis
      gene. The mutant mice developed significantly smaller lesions than the wild-type
      mice at the earlier stage of infection with the intracellular protozoan parasite
      Leishmania major. However, while all the wild-type mice achieved complete lesion
      resolution, the disease in the mutant mice progressed inexorably. The mutant mice
      had more IL-12 and nitrite/nitrate in the serum than wild-type mice following
      infection. Lymphoid cells from infected MRL/lpr mice produced more IFN-gamma but
      less IL-4 and IL-5 than cells from MRL-+/+ mice. Peritoneal macrophages from the
      mutant mice also produced more IL-12 and NO after stimulation with LPS. Thus, Fas
      expression is essential for resistance against leishmaniasis, and Fas-mediated
      apoptosis may form an integral part of the Th1-mediated microbicidal function.

PMID- 9574512
TI  - Characterization of an associated 16-kDa tyrosine phosphoprotein required for Ly
      49D signal transduction.
AB  - Ly-49D is an activating receptor on NK cells that does not become tyrosine
      phosphorylated upon activation. This report demonstrates that immunoprecipitation
      of Ly-49D, following pervanadate treatment or specific Ab cross-linking,
      coprecipitates a 16-kDa tyrosine-phosphorylated protein (pp16). Immunoblotting
      experiments and data from TCR-zeta/Fc epsilonRIgamma double knockout mice confirm
      that pp16 is not TCR-zeta, TCR-eta, or Fc epsilonRIgamma. Association of pp16
      with Ly-49D involves a transmembrane arginine since mutation to leucine (Ly
      49D[R54L]) abolishes association with pp16 in transfected P815 cells. In
      addition, Ly-49D(R54L) transfectants fail to mediate Ca2+ mobilization following
      Ab cross-linking. Therefore, signaling through Ly49D on NK cells depends on
      association with a distinct tyrosine phosphoprotein (pp16) in a manner analogous
      to that of TCR and FcR. Expression of this novel signaling peptide in both the NK
      and myeloid lineages indicates that pp16 is likely involved in the signal
      transduction cascade of additional receptor families.

PMID- 9574513
TI  - IL-4 induces functional cell-surface expression of CXCR4 on human T cells.
AB  - Here we report that IL-4 specifically enhances cell surface expression of CXCR4
      on resting peripheral and cord blood T cells. Whereas polarized Th2 clones
      express variable levels of CXCR4, expression of this receptor is undetectable on
      polarized Th1 clones but can be induced on the latter cells as well, following
      short-term culture in the presence of IL-4. The IL-4-induced CXCR4 is functional
      since interaction with its ligand, stromal-derived factor (SDF)-1, activates the
      p42 MAP-kinase ERK-2. In addition, although CXCR4 expression is down-regulated
      following stimulation of T cells and T cell clones via CD28 or CD3 and CD2 cell
      surface molecules, respectively, it is re-induced by IL-4. These data indicate an
      important role for IL-4 in rendering CD4+ T cells susceptible to infection with
      HIV via CXCR4, as well as in promoting SDF-1-induced migration of these cells.

PMID- 9574514
TI  - Technical note: Aberrant detection of cell surface Fas ligand with anti-peptide
      antibodies.
AB  - Polyclonal rabbit Abs raised against peptides from the C-terminal region (the
      extracellular domain) of human Fas ligand were produced for the detection of the
      molecule in Western blot analysis and immunohistochemistry. These Abs have been
      used by several groups of investigators to assess cell surface Fas ligand via
      flow cytometry, but we show that these polyclonal rabbit Abs do not detect cell
      surface Fas ligand by that technique.

PMID- 9574515
TI  - Hybrid membrane IgM with the transmembrane region of I-A alpha facilitates
      enhanced presentation of distinct epitopes to T cells.
AB  - The role of B cell Ag receptors (membrane Ig or mIg) in the efficient Ag
      presentation to T cells, including the requirement of mIgM-associated Ig
      alpha/Igbeta, remains unclear. We report here that mIgM, substituted with greater
      than two-thirds of the NH2-terminal A alpha transmembrane (TM) regions of the MHC
      class II molecule, are capable of mediating the efficient presentation of
      specific Ag to some (Group 1) but not all (Group 2) T cell hybridomas. In
      contrast, the generation of epitopes recognized by the Group 2 hybridomas can be
      mediated only by the wild-type mIgM. Tyrosine phosphorylation appears to be
      necessary for the enhanced Ag presentation to Group 2 hybridomas, while it does
      not for Group 1 hybridomas. In addition, differential sensitivity of Ag
      processing to leupeptin, different duration required for epitope
      generation/presentation, as well as the involvement of distinct epitopes for
      stimulation of these groups of T cell hybridomas were observed. These results
      suggest that transport of the mIgM/Ag complexes to an endocytic compartment(s)
      for generation of certain T cell epitopes may be mediated by the N-terminal TM
      sequence of mIgM, independent of Ig alpha/Igbeta association. This function can
      be replaced by two-thirds of the NH2-terminal TM region of A alpha chain of class
      II molecules.

PMID- 9574516
TI  - Polymorphism at the HLA-DQ locus determines susceptibility to experimental
      autoimmune myasthenia gravis.
AB  - Studies in myasthenia gravis (MG) patients demonstrate that polymorphism at the
      HLA-DQ locus influences the development of MG. Several studies using the mouse
      models also demonstrate the influence of class II molecules, especially the H2-A,
      which is the mouse homologue of HLA-DQ, in experimental autoimmune myasthenia
      gravis (EAMG). We used transgenic mice expressing two different DQ molecules, DQ8
      (DQA1*0301/B1*0302) and DQ6 (DQA1*0103/B1*0601), to evaluate the role of HLA-DQ
      genes in MG. These mice do not express endogenous mouse class II molecules since
      they contain the mutant H2-A beta0 gene. The mice were immunized with Torpedo
      acetylcholine receptor, and EAMG was assessed by clinical evaluation and was
      confirmed by electrophysiology. Clinical scores for EAMG were highest in HLA-DQ8
      transgenic mice, whereas the scores of HLA-DQ6 mice rarely exceeded grade 1.
      There was no incidence of EAMG in class II-deficient (H2-A beta0) mice. These
      results demonstrate that polymorphism at the HLA-DQ locus affects the incidence
      and the severity of EAMG. The manifestation of susceptibility to EAMG in the
      context of human class II molecules underscores the important roles of these
      molecules in the initiation and perpetuation of EAMG.

PMID- 9574517
TI  - Inhibition of mitogen-activated protein kinase kinase blocks T cell proliferation
      but does not induce or prevent anergy.
AB  - Three mitogen-activated protein kinase pathways are up-regulated during the
      activation of T lymphocytes, the extracellular signal-regulated kinase (ERK), Jun
      NH2-terminal kinase, and p38 mitogen-activated protein kinase pathways. To
      examine the effects of blocking the ERK pathway on T cell activation, we used the
      inhibitor U0126, which has been shown to specifically block mitogen-activated
      protein kinase/ERK kinase (MEK), the kinase upstream of ERK. This compound
      inhibited T cell proliferation in response to antigenic stimulation or cross
      linked anti-CD3 plus anti-CD28 Abs, but had no effect on IL-2-induced
      proliferation. The block in T cell proliferation was mediated by down-regulating
      IL-2 mRNA levels. Blocking Ag-induced proliferation by inhibiting MEK did not
      induce anergy, unlike treatments that block entry into the cell cycle following
      antigenic stimulation. Surprisingly, induction of anergy in T cells exposed to
      TCR cross-linking in the absence of costimulation was also not affected by
      blocking MEK, unlike cyclosporin A treatment that blocks anergy induction. These
      results suggest that inhibition of MEK prevents T cell proliferation in the short
      term, but does not cause any long-term effects on either T cell activation or
      induction of anergy. These findings may help determine the viability of using
      mitogen-activated protein kinase inhibitors as immune suppressants.

PMID- 9574518
TI  - Activation of p21-CDC42/Rac-activated kinases by CD28 signaling: p21-activated
      kinase (PAK) and MEK kinase 1 (MEKK1) may mediate the interplay between CD3 and
      CD28 signals.
AB  - CD28, a T cell costimulatory receptor, provides a signal that induces both
      optimal proliferation and the production of IL-2 by TCR-activated T cells. We
      show that the stimulation of CD28 leads to the activation of p21-activated kinase
      and MEK kinase 1. The same pathway was also stimulated in T cells treated with
      the cell-permeable ceramide analogue, C2-ceramide. The combined stimulation of
      either CD3 and CD28 or CD3 concurrently with C2-ceramide largely enhanced the
      activity of p21-activated kinase and MEK kinase 1. Therefore the Rac1/CDC42
      coupled pathway(s) is a candidate that transduces and facilitates cross-talk
      between the CD28 costimulatory signal and the TCR signal.

PMID- 9574519
TI  - Expression of ADP-ribosyltransferase on normal T lymphocytes and effects of
      nicotinamide adenine dinucleotide on their function.
AB  - ADP-ribosyltransferase (ADPRT) is a glycosylphosphatidylinositol-anchored cell
      surface enzyme on CTL. Expression of this enzyme correlates with suppression of
      CTL functions in the presence of its substrate beta-nicotinamide adenine
      dinucleotide (NAD). To investigate the immunoregulatory importance of ADPRT on
      normal lymphocytes in vivo, NAD was injected into mice and the effects on cell
      mediated and humoral immunity were assessed. Induction of both delayed-type
      hypersensitivity and CTL, but not Ab responses, are shown to be suppressed by
      NAD. Consistent with this, mature T cells, but not B cells or macrophages,
      express ADPRT and are able to ADP-ribosylate cell surface proteins. ADP
      ribosylated molecules were identified as LFA-1, CD8, CD27, CD43, CD44, and CD45.
      Concomitant to ADP-ribosylation of these molecules, T cell trafficking to
      secondary lymphoid organs is suppressed by NAD. To examine whether this is due to
      effects of NAD on cell activation, Ag-stimulated responses were assayed in vitro.
      NAD is shown to inhibit induction of cell proliferation, cytotoxicity, and
      cytokine secretion. It is suggested that ADPRT regulates T cells on the level of
      transmembrane signaling via ADP-ribosylation of cell surface molecules. This
      effect is reported to be indirect, as it involves transmission of signals through
      TCRs, which are not ADP-ribosylated.

PMID- 9574520
TI  - Mechanisms of CD8beta-mediated T cell response enhancement: interaction with MHC
      class I/beta2-microglobulin and functional coupling to TCR/CD3.
AB  - CD8beta expression results in enhanced IL-2 production and/or altered specificity
      in allogeneic MHC class I-restricted T cell hybridomas. Expression of chimeric
      CD8beta-alpha molecules (extracellular CD8beta, transmembrane and cytoplasmic
      CD8alpha) also results in enhancement of T hybridoma responses to alloantigen,
      suggesting that at least part of CD8beta's ability to influence responses similar
      to those of mature CD8+ T cells is mediated by its extracellular domain. Current
      data suggest that CD8beta-mediated response enhancement proceeds through
      mechanisms similar to those mediated by CD8alpha, i.e., interacting with MHC
      class I and stabilizing CD8-associated Lck activity. In this study we present
      evidence that the extracellular portion of CD8beta is capable of independent
      interaction with MHC class I/beta2m dimers in the absence of CD8alpha. In
      addition, CD8beta may enhance interaction with MHC class I/beta2m when associated
      with CD8alpha. We also present evidence from T hybridoma responses suggesting
      that the extracellular portion of CD8beta is uniquely capable of efficient
      interaction with the TCR/CD3 complex and may couple the TCR/CD3 complex to other
      surface components capable of enhancing TCR-mediated signals. This represents the
      first evidence that a critical coreceptor function can be preferentially
      associated with the CD8beta subunit.

PMID- 9574522
TI  - Newborn mice develop balanced Th1/Th2 primary effector responses in vivo but are
      biased to Th2 secondary responses.
AB  - Newborn mice are impaired in their abilities to mount protective immune
      responses. For decades, it was generally held that the poor responses of newborns
      were largely due to the developmentally immature state of the T cells. In vitro
      studies showing that neonatal T cells were deficient in Th1 cytokine production,
      proliferation, and secondary responsiveness strongly supported this idea.
      Recently, several studies have challenged this view; animals exposed to Ag as
      neonates were shown to have mature Th1 responses in adulthood. However, it is not
      clear whether the mature immune responses were actually mounted by T cells
      generated after the neonatal stage. We have reexamined this issue by analyzing
      the capabilities of neonatal lymph node T cells to develop into Ag-specific
      effector cells during the actual neonatal period. Our results demonstrate that
      the capacity to develop a balanced Th1/Th2 primary effector response is fully
      mature within the first week of life. However, while neonatal and adult primary
      cytokine profiles were very similar, Th2 secondary responses predominated in
      animals first immunized as newborns. Moreover, we have observed other differences
      between adults and neonatal responses, including 1) the kinetics of cytokine
      production and responsiveness to adjuvant during the primary response, and 2) the
      contribution of spleen and lymph node to secondary responses. We propose that
      these differences reflect developmental regulation of effector cell function that
      has important consequences to neonatal immune function.

PMID- 9574521
TI  - Differential requirements for LFA-1 binding to ICAM-1 and LFA-1-mediated cell
      aggregation.
AB  - Cellular adhesion through the beta2 integrin lymphocyte function-associated Ag
      (LFA)-1 is a complex event involving activation, ligand binding, and cell shape
      changes that ultimately result in enhanced adhesion. In this report we define
      requirements for ligand binding and post receptor signaling by comparing two
      mechanisms of activation of LFA-1: 1) inside-out signaling and 2) direct
      activation by the beta2 Ab, CBR LFA-1/2. Our results demonstrate that activation
      of LFA-1 binding to ICAM-1 by CBR LFA-1/2, in contrast to inside-out signaling
      mechanisms, does not require protein kinase C activation or protein phosphatase
      2A activity nor is it affected by agents that interfere with reorganization of
      the cytoskeleton. Inhibition of protein tyrosine kinase activity does not affect
      ICAM- binding by either mechanism of activation. However, activation by either
      mode does require the presence of the beta cytoplasmic domain; deletion of the C
      terminal phenylalanine or the five amino acid stretch between 756-762 abolished
      activation of LFA-1. This, combined with the observation that intracellular
      energy pools must be preserved, implicates the beta cytoplasmic domain in a key
      energy-dependent conformational change in LFA-1 that is required to achieve
      enhanced ligand binding. Post ligand binding events induced by both PMA and Ab
      stimulation, as measured by homotypic aggregation, require protein tyrosine
      kinase, phosphatase, and RhoA activities. By examining both ligand binding and
      aggregation, we have been able to dissect the signaling components critical in
      the multistep process of LFA-1-mediated cellular adhesion.

PMID- 9574523
TI  - Involvement of CD40 ligand-CD40 and CTLA4-B7 pathways in murine acute graft
      versus-host disease induced by allogeneic T cells lacking CD28.
AB  - The blockade of B7, using B7 antagonists such as anti-CD80 and/or -CD86 mAbs or
      CTLA4Ig in vivo, has been shown to induce an efficient suppression of T cell
      mediated immune responses in allograft, allergy, and autoimmune models. However,
      this treatment does not result in complete tolerance. In this study, we examined
      CD28-B7-independent activation pathways in the pathogenesis of graft-vs-host
      disease (GVHD) using allogeneic T cells from CD28-deficient mice. Acute GVHD was
      induced in the absence of CD28 on donor T cells and its manifestations were
      obvious in the lymphoid tissues. The CD28-independent GVHD was significantly
      improved by treatment with anti-CD40 ligand (CD40L) mAb. In contrast, treatment
      with anti-CD80 plus anti-CD86 mAbs exacerbated the clinical manifestations of
      GVHD and increased the T cell response against host alloantigen, resulting in the
      expression of CTLA4, CD40L, and CD25 on splenic T cells. These data suggested
      that the CD40L-CD40 pathway significantly contributed to the CD28-independent
      pathogenesis of acute GVHD, whereas the CTLA4-B7 pathway acted protectively in
      the development of GVHD. These results imply that selectively blockading CD28,
      instead of disrupting both CD28 and CTLA4, would be a better therapeutic strategy
      for GVHD. Additionally, the simultaneous use of CD40 antagonists may be
      advantageous.

PMID- 9574524
TI  - Oligoclonal development of B cells bearing discrete Ig chains in chicken single
      germinal centers.
AB  - Chicken single germinal centers enable us to analyze the postbursal
      diversifications of B cells due to their easy isolation. Germinal center
      formation has peaked by day 7 of primary responses and begins to wane 14 days
      after immunization. To detail the kinetics of Ig mutation and selection, we
      analyzed Ig light chain sequences recovered from single germinal centers at 7 and
      11 days postimmunization with an artificial Ag. Our observations show that
      multiple, Ag-activated B cells migrating into single germinal centers are
      diversified by gene conversion in the very early phase of the germinal center
      reaction and are subsequently subjected to point mutations and selection for
      oligoclonality.

PMID- 9574525
TI  - Costimulation via TCR and IL-1 receptor reveals a novel IL-1alpha-mediated
      autocrine pathway of Th2 cell proliferation.
AB  - Previous studies have shown that triggering of Th2 cells via the TCR is
      sufficient for production of IL-4 but not for proliferation of these cells.
      Proliferation of Th2 cells occurs only in the additional presence of a
      costimulatory signal delivered by IL-1. For the majority of Th2 cell clones, this
      type of proliferation was found to be independent of IL-4. Here, we further
      investigated the mechanism of IL-4-independent proliferation. We demonstrate
      that, after costimulation via TCR and IL-1R, but not via either receptor alone,
      Th2 cells are triggered to produce cell-associated IL-1alpha, as detected at the
      level of function, protein, and mRNA expression. In the presence of the TCR
      signal, autocrine IL-1alpha is then able to costimulate IL-4-independent
      proliferation of Th2 cells and to further enhance its own production. Thus, our
      results point to a novel, IL-4-independent, self-amplifying autocrine pathway of
      Th2 cell proliferation that requires a signal via the TCR and a costimulatory
      signal via IL-1R. This pathway may explain frustrating results in experimental
      models that attempted to treat established Th2-mediated diseases in vivo with IL
      4-neutralizing agents alone.

PMID- 9574526
TI  - Matrix metalloproteinases produced by rat IL-2-activated NK cells.
AB  - We have previously documented that adoptively transferred IL-2-activated NK (A
      NK) cells can accumulate within cancer metastases. Electron microscopic studies
      of pulmonary metastases have revealed that adoptively transferred A-NK cells that
      accumulate within metastases bind to endothelial cells and are able to traverse
      basement membranes. We have now extended these morphologic studies. We report
      that rat A-NK cells produce two matrix metalloproteinases: MMP-2 and MMP-9, as
      determined by SDS-PAGE gelatin zymography. These activities are inhibited
      following incubation with BB-94 (batimastat), a specific inhibitor of matrix
      metalloproteinases but not with 3,4-dichloroisocoumarin, an inhibitor of neutral
      serine proteases. The identity of MMP-2 was confirmed by Western blots using a
      polyclonal Ab against human MMP-2, whereas reverse transcriptase-PCR analysis of
      mRNA extracts of A-NK cells has confirmed the presence of MMP-9. In addition, we
      report for the first time that A-NK cells can migrate through a model basement
      membrane-like extracellular matrix. Moreover, the ability of A-NK cells to
      migrate through this model basement membrane was partially inhibited by BB-94;
      however, BB-94 has no effect on A-NK cell-mediated cytotoxicity, suggesting that
      matrix metalloproteinases do not contribute to cytolytic function of A-NK cells.
      In sum, our studies show that A-NK cells employ BB-94-inhibitable matrix
      metalloproteinases to degrade extracellular matrices. This suggests that matrix
      metalloproteinases may play a role in the accumulation of A-NK cells within
      cancer metastases.

PMID- 9574527
TI  - Extensive junctional diversity of Ig heavy chain rearrangements generated in the
      progeny of single fetal multipotent hematopoietic cells in the absence of
      selection.
AB  - We analyzed the progeny of individual multipotent hemopoietic cells, derived from
      the para-aortic splanchopleura, the earliest identified source of lymphocyte
      precursors in pre-liver mouse embryos. Single precursors were expanded in an in
      vitro culture system that permits both commitment and differentiation of B cell
      precursors. We show that from one single multipotent progenitor we could obtain
      large numbers of B cell precursors that rearrange the Ig heavy chain genes and
      generate a repertoire as diverse as that observed in adult populations. N region
      additions are present at V(D)J junctions, showing that terminal deoxynucleotidyl
      transferase expression has been switched on and is not, consequently, an
      intrinsic property of adult stem cells. Throughout the culture period, cells show
      a majority of DJ vs V(D)J rearrangements and a ratio of 2:1 of nonproductive to
      productive V(D)J rearrangements, which is close to the expected frequency in the
      absence of selection. In addition, counterselection for D-J rearrangements in
      reading frame 2 is observed in V(D)J joints, and allelic exclusion was
      consistently observed. We conclude that of the three events associated with heavy
      chain rearrangement, two of them, namely allelic exclusion and counterselection
      of cells in which the D segment is in reading frame 2, are intrinsic to the cell,
      while selection of productive heavy chain rearrangements is induced in the bone
      marrow environment.

PMID- 9574528
TI  - Ultraviolet light-induced immune tolerance is mediated via the Fas/Fas-ligand
      system.
AB  - Hapten sensitization through UV-exposed skin induces tolerance that is mediated
      via the induction of hapten-specific T suppressor cells. However, the detailed
      mechanisms underlying tolerance induction remain unclear to date. We show here
      that the apoptosis-related surface Ag Fas (APO-1, CD95) and its ligand, Fas
      ligand (FasL) are critically involved, since Fas-deficient lpr mice and FasL
      deficient gld mice do not develop UV-induced tolerance. Adoptive transfer
      experiments revealed that the mediation of tolerance does not require the
      expression of Fas or FasL by the T suppressor cells but does require the
      expression of both molecules by the cells of mice receiving the T suppressor
      cells. To identify the mechanisms involved, the effect of suppressor cells on Ag
      presenting dendritic cells (DC) was studied. Coincubation of hapten-pulsed DC
      with T cells that were obtained from UV-tolerized mice resulted in an enhanced
      death rate of DC, and this cell death was dependent upon Fas expression. The
      addition of IL-12, which recently was found to break established tolerance in
      vivo, prevented DC death. Moreover, IL-12 did not only rescue DC from T
      suppressor cell-induced death but also from apoptosis induced by rFasL,
      suggesting that IL-12 may interfere with the Fas/FasL system. Together, these
      data indicate a crucial role for the Fas/FasL system in UV-induced tolerance, and
      suggest that UV-induced T suppressor cells may act by inducing the cell death of
      APCs via the Fas pathway. The ability of IL-12 to break established tolerance may
      be due to the prevention of DC death induced by T suppressor cells.

PMID- 9574529
TI  - Presentation of proteolipid protein epitopes and B7-1-dependent activation of
      encephalitogenic T cells by IFN-gamma-activated SJL/J astrocytes.
AB  - There is controversy regarding the possible role of glial cells as APCs in the
      pathogenesis of central nervous system (CNS) demyelinating diseases such as
      multiple sclerosis and its animal model, experimental autoimmune
      encephalomyelitis (EAE). Microglia have been clearly shown to present Ag in the
      CNS, and due to the proximity of activated astroglial cells to infiltrating T
      cells and macrophages in demyelinating lesions, it is also possible that
      astrocytes positively or negatively regulate disease initiation and/or
      progression. We examined the capacity of IFN-gamma-treated astrocytes from EAE
      susceptible SJL/J mice to process and present myelin epitopes. IFN-gamma
      activation up-regulated ICAM-1, VCAM-1, MHC class II, invariant chain, H2-M,
      CD40, and B7-1 as determined by FACS and/or RT-PCR analyses. B7-2 expression was
      only marginally enhanced on SJL/J astrocytes. Consistent with the expression of
      these accessory molecules, IFN-gamma-treated SJL/J astrocytes induced the B7-1
      dependent activation of Th1 lines and lymph node T cells specific for the
      immunodominant encephalitogenic proteolipid protein (PLP) epitope (PLP139-151) as
      assessed by proliferation and activation for the adoptive transfer of EAE.
      Interestingly, IFN-gamma-activated astrocytes efficiently processed and presented
      PLP139-151, but not the subdominant PLP178-191, PLP56-70, or PLP104-117 epitopes,
      from intact PLP and a recombinant variant fusion protein of PLP (MP4). The data
      are consistent with the hypothesis that astrocytes in the proinflammatory CNS
      environment have the capability of activating CNS-infiltrating encephalitogenic T
      cells specific for immunodominant epitopes on various myelin proteins that may be
      involved in either the initial or the relapsing stages of EAE.

PMID- 9574530
TI  - TNF-alpha messenger RNA and protein expression in the uteroplacental unit of mice
      with pregnancy loss.
AB  - An elevated expression of TNF-alpha in embryonic microenvironment was found to be
      associated with postimplantation loss. In this work, we examined the pattern of
      TNF-alpha expression at both the mRNA and the protein level as well as the
      distribution of TNF-alpha receptor mRNA in the uteroplacental unit of mice with
      induced (cyclophosphamide-treated) or spontaneous (CBA/J x DBA/2J mouse
      combination) pregnancy loss. RNase protection analysis demonstrated an increase
      in TNF-alpha mRNA expression in the placentae of mice with pregnancy loss
      compared with that in control mice. TNF-alpha messages were localized to the
      uterine epithelium and stroma as well as the giant and spongiotrophoblast cells
      of the placenta. The intensity of the hybridization signal in placentae of mice
      with pregnancy loss was substantially higher than that in control mice. The up
      regulation of TNF-alpha mRNA was accompanied by an increase in the expression of
      TNF-alpha receptor I mRNA in the same cell populations. The elevation of TNF
      alpha production was also demonstrated at the protein level. Western blot
      analysis showed an increased level of the 18- and 26-kDa TNF-alpha protein
      species in the uteroplacental unit of mice with pregnancy loss. Immunostaining
      revealed TNF-alpha-positive leukocytes located in the uterus and placenta.
      Finally, we found that immunization of mice with cyclophosphamide-induced
      pregnancy loss while decreasing the resorption rate in these females resulted in
      a decline in TNF-alpha expression at the fetomaternal interface. These data
      clearly suggest an involvement of TNF-alpha in pathways leading to both
      spontaneous and induced placental death.

PMID- 9574532
TI  - Type I IFNs inhibit human dendritic cell IL-12 production and Th1 cell
      development.
AB  - We have investigated the role of type I IFNs (IFN-alpha and -beta) in human T
      cell differentiation using anti-CD3 mAb and allogeneic, in vitro-derived
      dendritic cells (DC) as APCs. DC were very efficient activators of naive CD4+ T
      cells, providing necessary costimulation and soluble factors to support Th1
      differentiation and expansion. Addition of IFN-alphabeta to DC/T cell cultures
      resulted in induction of T cell IL-10 production and inhibition of IFN-gamma, TNF
      alpha, and LT secretion. Diminished T cell IFN-gamma production correlated with
      IFN-alphabeta-mediated inhibition of the p40 chain of the IL-12 heterodimer
      secreted by DC. Suppression of p40 IL-12 and IFN-gamma was not due to increased
      levels of IL-10 in these cultures, and production of IFN-gamma could be restored
      by exogenous IL-12. These data indicate that type I IFNs inhibit DC p40 IL-12
      expression, which is required for development of IFN-gamma-producing CD4+ T
      cells. Furthermore, when T cells were restimulated without IFN-beta, these cells
      induced less p40 IL-12 from DC, suggesting that the functional properties of T
      cells may regulate DC function. Thus, IFN-alphabeta inhibits both IL-12-dependent
      and independent Th1 cytokine production and provides a mechanism for inhibition
      of IL-12-mediated immunity in viral infections.

PMID- 9574531
TI  - Novel glycosylation of HLA-DRalpha disrupts antigen presentation without altering
      endosomal localization.
AB  - The HLA-DR hemizygous B lymphoblastoid cell line, 10.24.6, has a DRA mutation
      (Pro96-->Ser) that creates a novel glycosylation site at Asn94. The mutant DR
      molecules are primarily associated with nested fragments of invariant chain
      (class II-associated invariant chain peptides), and their interaction with HLA-DM
      is impaired. Here we further analyzed the defect in 10.24.6 cells. Expressing
      Ser96 mutant DRA cDNA in DRA-null cells recapitulated the 10.24.6 phenotype,
      indicating that the mutation causes the Ag presentation defect. A mutation to
      Ala96alpha, which does not introduce an extra glycan, generated a normal
      phenotype; the critical role of the glycan was further supported by experiments
      in which N-glycosylation was blocked by tunicamycin. We also evaluated whether
      the 10.24.6 mutation affected DR3 maturation or trafficking. Metabolic labeling
      and subcellular fractionation showed that assembly, endosomal transport, and
      invariant chain proteolysis of mutant DR3 molecules were similar to wild-type. A
      slight delay in export from the endoplasmic reticulum to the Golgi apparatus in
      10.24.6 cells probably did not contribute significantly to the Ag presentation
      defect, because the abundance of DM and mutant DR in peptide-loading compartments
      was normal at steady state. Our results indicate that proper localization of
      these molecules does not depend on their interaction.

PMID- 9574533
TI  - TAP-independent MHC class I peptide antigen presentation to alloreactive CTL is
      enhanced by target cell incubation at subphysiologic temperatures.
AB  - We investigated the peptide dependency of a group of CD8+ anti-HLA-B7
      alloreactive CTL. The CTL killed target cells after acid denaturation of more
      than 98% of target cell surface peptide/MHC class I complexes. The CTL also
      killed TAP- HLA-B7-transfected T2 (T2B7) cells. The killing was enhanced by
      target cell incubation at 26 degrees C. Despite these findings, which suggested
      peptide-independent allorecognition, CTL-mediated cytolysis was reduced or
      abolished by several point mutations affecting the HLA-B7 peptide-binding groove.
      Acid denaturation of HLA complexes on T2B7 cells prohibited CTL recognition. CTL
      recognition was restored by T2B7 cell incubation with beta2-microglobulin and a
      single HPLC fraction containing peptides extracted from TAP+HLA-B7+ cells, but
      not by any of a panel of 17 synthetic HLA-B7-binding peptides. These findings
      indicated that CTL allorecognition was peptide specific. Sensitizing peptide was
      extracted from T2B7 cells only after incubation at 26 degrees C. The amount of
      peptide detected in TAP+ cells was at least 10-fold and 100-fold greater than
      that detected in TAP- cells incubated at 26 degrees C and at 37 degrees C,
      respectively. TAP-independent peptide epitope presentation was sensitive to
      treatment with brefeldin A, but not sensitive to treatment with chloroquine,
      consistent with an endogenous peptide source. We propose that subphysiologic
      temperature incubation can enhance peptide/MHC class I presentation in the total
      absence of TAP function.

PMID- 9574534
TI  - A noncomitogenic CD2R monoclonal antibody induces apoptosis of activated T cells
      by a CD95/CD95-L-dependent pathway.
AB  - Clonal expansion of activated T and B cells is controlled by homeostatic
      mechanisms resulting in apoptosis of a large proportion of activated cells,
      mostly through interaction between CD95 (Fas or Apo-1) receptor and its ligand
      CD95-L. CD2, which is considered as a CD3/TCR alternative pathway of T cell
      activation, may trigger activation-induced cell death, but the role of CD95/CD95
      L interaction in CD2-mediated apoptosis remains controversial. We show here that
      the CD2R mAb YTH 655.5, which does not induce comitogenic signals when associated
      with another CD2 mAb, triggers CD95-L expression by preactivated but not resting
      T cells, resulting in CD95/CD95-L-mediated apoptosis. The critical role of
      CD95/CD95-L interaction was supported by complete inhibition in the presence of
      the antagonist CD95 mAb ZB4 and by blocking CD95-L synthesis and surface
      expression by cycloheximide, cyclosporin A, EGTA, or cytochalasin B. YTH 655.5
      was shown to stimulate p56lck phosphorylation and enzymatic activity. However,
      p56lck activation is not sufficient to trigger apoptosis, because other CD2R and
      CD4 mAbs that activate p56lck do not induce apoptosis. In conclusion, CD2 can
      mediate nonmitogenic signals, resulting in CD95-L expression and apoptosis of
      CD95+ cells.

PMID- 9574536
TI  - Induction of Fas ligand in murine bone marrow NK cells by bacterial
      polysaccharides.
AB  - Bacterial polysaccharides have a wide range of activities in mammals. We have
      studied the effect of LPS and poly-beta-(1-->4)-D-mannuronate (mannuronan, poly
      M), an exopolysaccharide from Pseudomonas aeruginosa, on the cytotoxicity
      mediated by murine bone marrow cells (BMC). Addition of LPS or mannuronan to BMC
      induced a time- and dose-dependent cytotoxicity against Jurkat cells. The LPS- or
      mannuronan-induced cytotoxicity was due to increased Fas ligand (FasL) expression
      by BMC, since 1) Fas-transfected L1210-Fas target cells were more susceptible to
      lysis than the Fas(low)-expressing parent L1210 cells, 2) stimulated BMC from
      FasL-defective gld/gld mice were not cytolytic and, 3) the cytolytic activity of
      normal BMC was inhibited by a Fas-Fc fusion protein. Flow cytometry showed an
      increase in surface FasL in LPS-stimulated BMC. RT-PCR analysis of BMC revealed
      constitutive expression of FasL mRNA, which was increased after LPS stimulation.
      Immunomagnetic depletion of NK1.1-, CD2-, or CD32/16-expressing cells from BMC
      abrogated the LPS-induced BMC cytotoxicity against L1210-Fas cells, suggesting
      that NK cells were the cytotoxic effector cells. Depletion of CD45R/B220-, Gr-1-,
      or CD11b/Mac-1-expressing cells only partially decreased BMC-mediated
      cytotoxicity, and depletion of CD4- or CD8a-expressing cells had no effect. The
      results support the conclusion that LPS and mannuronan induce expression of
      cytotoxic FasL on bone marrow NK cells.

PMID- 9574535
TI  - IL-15 enhances the response of human gamma delta T cells to nonpeptide
      [correction of nonpetide] microbial antigens.
AB  - Human gamma delta T cells have the ability to rapidly expand and produce IFN
      gamma in response to nonpeptide Ags of microbial pathogens, in particular a class
      of compounds known as the prenyl phosphates. We investigated the ability of IL
      15, a T cell growth factor, to modulate prenyl phosphate-induced gamma delta T
      cell proliferation and cytokine production. IL-15 significantly enhanced the
      expansion of gamma delta T cells in the peripheral blood after stimulation in
      vitro with isopentenyl pyrophosphate. Moreover, using gamma delta T cell clones,
      we determined that IL-15-induced T cell proliferation was dependent on the IL-2R
      beta chain but not the IL-2R alpha chain. We therefore studied the IL-15R alpha
      chain expression in human gamma delta T cells in the presence or absence of
      nonpeptide Ags. We found IL-15R alpha mRNA expression in IL-15-stimulated and Ag
      stimulated human gamma delta T cells but not in resting gamma delta T cells.
      Although IL-15 itself had little effect on the production of IFN-gamma, IL-15
      plus IL-12 acted synergistically to augment IFN-gamma production by gamma delta T
      cells. Moreover, we showed that this increase in IFN-gamma could be explained by
      the dual activation of STAT1 and STAT4 by IL-15 and IL-12, respectively. Taken
      together, these results suggest that IL-15 may contribute to activation of human
      gamma delta T cells in the immune response to microbial pathogens.

PMID- 9574537
TI  - Analysis of the IFN-gamma-signaling pathway in macrophages at different stages of
      maturation.
AB  - We previously demonstrated that the macrophage cell lines RAW 264.7 and WEHI-3
      exhibit distinct patterns of gene expression in response to IFN-gamma. This
      difference is controlled at the transcriptional level and results from a specific
      inability of the less mature WEHI-3 cells to utilize either the IFN-stimulated
      response element or the gamma-activated sequence DNA regulatory element in
      response to stimulation with IFN-gamma, while other aspects of IFN-gamma gene
      induction remain intact. In the work described here, we examined the components
      of the IFN-gamma signal transduction pathway in RAW 264.7 and WEHI-3 cells to
      determine whether differences in pathway components or activity exist in WEHI-3
      cells that could give rise to this difference in transcriptional response.
      Reverse transcriptase-PCR (RT-PCR) and flow cytometric analyses indicated that
      the levels of IFN-gamma receptor mRNA accumulation and protein expression are
      comparable for RAW 264.7 and WEHI-3 cells. RT-PCR and immunoblot analyses
      revealed that the principal components of this signaling pathway, including JAK1,
      JAK2, and STAT1, are present in both RAW 264.7 and WEHI-3 cells. However,
      analysis of STAT1 DNA-binding activity by electrophoretic mobility shift assay
      and of STAT1 phosphorylation by immunoblot revealed that this DNA-binding factor
      is active in RAW 264.7, but not in WEHI-3, cells after IFN-gamma stimulation.
      These results demonstrate that the components of the IFN-gamma signal
      transduction pathway are intact in WEHI-3 cells, but stimulation of these cells
      by IFN-gamma does not result in STAT1 activation.

PMID- 9574538
TI  - The TCR-binding region of the HLA class I alpha2 domain signals rapid Fas
      independent cell death: a direct pathway for T cell-mediated killing of target
      cells?
AB  - TCR binding to an MHC class I/peptide complex is a central event in CTL-mediated
      elimination of target cells. In this study, we demonstrate that specific
      activation of the TCR-binding region of the HLA-A2 class I alpha2 domain induces
      apoptotic cell death. mAbs to this region rapidly induced apoptosis of HLA-A2
      expressing Jurkat E11 cells, as determined by morphologic changes,
      phosphatidylserine exposure on the cell surface, and propidium iodide uptake. In
      contrast, apoptosis was not induced following culture with mAbs directed to other
      regions of the class I molecule. Death signaling by class I molecules is
      apparently dependent on coreceptor activation, as apoptosis is also signaled by
      HLA-A2 molecules, where the intracytoplasmic residues were deleted. HLA class I
      alpha2-mediated cell death appeared to proceed independent of the Fas pathway.
      Compared with apoptotic signaling by Fas ligation, HLA class I alpha2-mediated
      responses displayed a faster time course and could be observed within 30 min.
      Furthermore, class I alpha2-induced cell death did not involve observable DNA
      fragmentation. The apoptotic response was not affected significantly by peptide
      inhibitors of IL-1beta converting enzyme (ICE)-like proteases and CPP32. Taken
      together, activation of the TCR-binding domain of the class I alpha2 helix may
      result in apoptotic signaling apparently dependent on a novel death pathway.
      Thus, target HLA class I molecules may directly signal apoptotic cell death
      following proper ligation by the TCR.

PMID- 9574539
TI  - Regulation of transcription of the TATA-less human complement component C4 gene.
AB  - The 5'-sequences flanking the human complement component C4 genes (C4A and C4B)
      have been analyzed for their ability to direct expression of a reporter gene in
      cell lines that constitutively express or do not express C4. No difference in the
      level of reporter gene expression was detected in cells transfected with C4A- or
      C4B-specific constructs. A series of reporter constructs containing progressively
      truncated C4 promoter fragments transfected into the hepatocyte Hep G2 cell line,
      identified the sequence contained within the region -178 to -39 as that
      associated with maximal reporter gene expression. This region contains consensus
      binding motifs for nuclear factor 1 (-110 to -97), Sp1 (-57 to -49), and three
      basic helix-loop-helix (-137 to -132, -98 to -93, and -78 to -73)-like
      transcription factors. Electromobility shift assays and DNase I footprinting
      analysis showed specific DNA-protein interactions of the C4 promoter at the
      nuclear factor 1, two E box (-98 to -93 and -78 to -73), and Sp1 binding domains.
      Site-directed mutagenesis of the Sp1 binding site resulted in total abrogation of
      reporter gene expression and mutation of the E box (-78 to -73) resulted in a 8
      fold reduction in expression. We conclude that the Sp1 binding site at position 
      57 to -49 is critical for accurately initiated, basal transcription of C4.

PMID- 9574540
TI  - The glycosylphosphatidylinositol-anchored form and the transmembrane form of CD58
      associate with protein kinases.
AB  - The significance of the glycosylphosphatidylinositol (GPI) anchor is unknown.
      Since GPI-anchored proteins mediate signaling, it has been suggested that the GPI
      structure serves as a signal-transducing element. However, the division of
      signaling functions between transmembrane and GPI-anchored proteins is unclear.
      Studies of distinct membrane-anchored forms of the same protein may resolve this
      issue. The adhesion molecule CD58 is expressed on the cell surface in both a
      transmembrane and a GPI-anchored form and hence provides a useful model. We
      studied CD58 in the human B lymphoblastoid cell line JY. In addition to mediating
      adhesion, CD58 is involved in signal transduction. Incubation of JY cells with
      immobilized anti-CD58 Abs results in extensive tyrosine phosphorylation and in
      secretion of TNF-alpha. We demonstrate that CD58 is associated with protein
      kinase(s) and with several kinase substrates. We further demonstrate that both
      CD58 isoforms are involved. CD58 in JY variant cells, which express only the
      transmembrane form, as well as CD58 in JY variant cells, which express only the
      GPI-anchored form, are associated with kinase activity. This association results
      in a phosphorylation pattern that is common to the variant and to wild-type JY
      cells. Thus, these findings suggest that the capacity of GPI-anchored proteins to
      interact with kinases is not always dependent on the GPI anchor itself.

PMID- 9574541
TI  - Evidence for sulfate modification of H-2Dd on N-linked carbohydrate(s): possible
      involvement in Ly-49A interaction.
AB  - Murine class I molecules are ligands for Ly-49 molecules, a family of regulatory
      receptors expressed on murine NK cells. Since soluble sulfated mono- and
      polysaccharides interfere with the interaction of Ly-49A, a C-type lectin, and
      its class I ligand, Dd, it is possible that the oligosaccharides on class I
      molecules are sulfated and participate in Ly-49A binding. In this report, we show
      that H-2Dd expressed by activated T cells and various tumor cell lines is
      sulfated, as demonstrated by immunoprecipitation of Dd following Na235SO4
      labeling. The 35SO4(-2) label on Dd expressed by a representative tumor cell,
      NZB1.1, is removed by peptide N-glycosidase F, but is resistant to
      endoglycosidase H treatment, indicating that the sulfate group is located on
      mature N-linked oligosaccharides. Two-dimensional SDS-PAGE analysis revealed that
      all major mature glycosylation variants of the Dd expressed by NZB1.1 are
      sulfated. Sodium chlorate, a potent inhibitor of ATP-sulfurylase, which prevents
      the formation of the sulfate donor, 3'-phosphoadenosine 5'-phosphosulfate,
      inhibited metabolic sulfation of Dd. NZB1.1 binds isolated Ly-49A immobilized on
      solid phase through an interaction by cell surface Dd, since cell adhesion was
      blocked by Abs directed against Dd or Ly-49A. Treatment of the Dd-expressing
      NZB1.1 tumor cells with sodium chlorate reduced their ability to bind immobilized
      Ly-49A, particularly when Ly-49A density was limiting. These results provide
      evidence for sulfation of H-2Dd oligosaccharide moieties, and suggest a role for
      this posttranslational modification in the interaction of Dd with Ly-49A.

PMID- 9574542
TI  - Interaction of HLA-E with peptides and the peptide transporter in vitro:
      implications for its function in antigen presentation.
AB  - The assembly of MHC Ia molecules in the endoplasmic reticulum requires the
      presence of peptide ligands and beta2m and is facilitated by chaperones in an
      ordered sequence of molecular interactions. A crucial step in this process is the
      interaction of the class I alpha-chain/beta2m dimer with TAP, which is believed
      to ensure effective peptide loading of the empty class I molecule. We have
      previously demonstrated impaired intracellular transport of the class Ib molecule
      HLA-E in mouse myeloma cells cotransfected with the genes for HLA-E and human
      beta2m, which is most likely attributable to inefficient intracellular peptide
      loading of the HLA-E molecule. We therefore analyzed the ability of HLA-E in the
      transfectant cell line to bind synthetic peptides by means of their ability to
      enhance cell surface expression of HLA-E. Peptide binding was confirmed by
      testing the effect on the thermostability of soluble empty HLA-E/human beta2m
      dimers. Two viral peptides binding to HLA-E were thus identified, for which the
      exact positioning of the N terminus appeared critical for binding, whereas the
      contribution of the length of the C terminus seemed to be minor, allowing
      peptides as short as seven amino acids and up to 16 amino acids to exhibit
      considerable binding activity. Furthermore, we demonstrate that HLA-E interacts
      with TAP and that this interaction can be prolonged by the proteasome inhibitor N
      acetyl-L-leucyl-L-leucyl-L-norleucinal, which reduces the intracellular peptide
      pool. The presented data indicate that HLA-E is capable of presenting peptide
      ligands similar to the repertoire of HLA class Ia molecules.

PMID- 9574543
TI  - Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules.
AB  - Copolymer 1 (Cop 1) is a random synthetic amino acid copolymer of L-alanine, L
      glutamic acid, L-lysine, and L-tyrosine, effective both in suppression of
      experimental allergic encephalomyelitis and in the treatment of relapsing forms
      of multiple sclerosis. Cop 1 binds promiscuously and very efficiently to living
      APCs of various HLA haplotypes. In the present study, a substantial part of the
      whole mixture of random polypeptides that compose Cop 1 was shown to bind to
      purified human HLA-DR1, DR2, and DR4 with high affinity in a temperature- and
      time (and, in the case of DR4, pH)-dependent manner, and was competitively
      inhibited by DR-restricted peptides, but not by peptide derivatives that bind
      with low affinity. Bacterial superantigens inhibited Cop 1 binding only at very
      high concentrations. The formation of the Cop 1-DR1 complex was also shown by SDS
      PAGE. These findings represent the first direct evidence for interactions of Cop
      1 with purified DR molecules, and suggest that its effectiveness in experimental
      allergic encephalomyelitis and multiple sclerosis may be directly related to its
      binding in the groove of HLA-DR proteins.

PMID- 9574544
TI  - Dominant signals leading to inhibitor kappaB protein degradation mediate CD40
      ligand rescue of WEHI 231 immature B cells from receptor-mediated apoptosis.
AB  - Recently, we demonstrated maintenance of nuclear factor (NF)-kappaB/Rel factors
      plays a major role in B cell survival. Treatment of WEHI 231 immature B cells
      with an Ab against the surface IgM protein (anti-IgM) induces apoptosis that can
      be rescued by engagement of CD40 receptor. The dramatic decrease in high basal
      levels of NF-kappaB/Rel activity induced by anti-IgM treatment led to cell death.
      CD40 ligand (CD40L) treatment prevented the drop in NF-kappaB/Rel factor binding
      by inducing a sustained decrease in inhibitor (I) kappaB-alpha and transient
      decrease in IkappaB-beta protein levels. In this study, we have investigated the
      regulation of these NF-kappaB/Rel-inhibitory proteins. In exponentially growing
      WEHI 231 cells, the IkappaB-alpha and IkappaB-beta proteins decayed with an
      approximate t1/2 of 38 and 76 min, respectively, which was blocked effectively
      upon addition of the proteasome-specific inhibitor (benzylcarbonyl)-Leu-Leu
      phenylalaninal (Z-LLF-CHO). Anti-IgM treatment stabilized IkappaB-alpha and
      IkappaB-beta proteins. CD40L treatment resulted in a dramatic decrease in t1/2 (<
      5 min) for both IkappaB molecules, which was inhibited by addition of Z-LLF-CHO.
      CD40L treatment also caused a delayed increase in IkappaB-beta mRNA levels, most
      likely contributing to the observed recovery of IkappaB-beta levels.
      Microinjection of IkappaB-alpha-glutathione S-transferase fusion protein into
      nuclei of WEHI 231 cells ablated protection by CD40L from receptor-mediated
      killing. Furthermore, CD40L rescued apoptosis induced upon microinjection of a
      vector expressing wild-type IkappaB-alpha, but not a 32A/36A mutant form of
      IkappaB-alpha, unable to be phosphorylated and hence degraded. Thus, control of
      turnover of IkappaB proteins by CD40L plays a major role in maintenance of NF
      kappaB/Rel and resultant rescue of WEHI 231 cells from apoptosis.

PMID- 9574545
TI  - Only selected light chains combine with a given heavy chain to confer specificity
      for a model glycopeptide antigen.
AB  - The M and N human blood group glycopeptide Ags are carried on RBCs by glycophorin
      A. Previous results suggested that the murine humoral immune response against the
      N, but not the M, Ag is restricted. In addition, these results suggested that
      particular highly homologous heavy chains might be able to combine promiscuously
      with various light chains to yield anti-N specificity. To examine this, the
      current study used Fab phage methodology to couple an array of light chains,
      obtained from cDNA libraries isolated from immunized mice, to single Fd obtained
      from N61, N92, and 425/2B hybridomas. Interestingly, for the chimeric Fab to
      retain M or N specificity, the new light chains needed to belong to the same Vk
      gene family as the light chain from the parental, hybridoma-derived mAb. In some
      cases the new light chains modified the Fab affinity and fine specificity. For
      example, library-derived light chains coupled with the N92 Fd yielded chimeric
      Fab with increased affinity. In particular, the affinity of these univalent
      chimeric Fab for the N Ag was equivalent to that of the bivalent parental IgG
      mAb. Taken together, these results demonstrate that particular structures formed
      by the light chain V region are required to cooperate with a particular heavy
      chain V region to create a functional binding site for these glycopeptide Ags.
      They also demonstrate a lack of heavy chain promiscuity in the formation of
      murine anti-M and anti-N Abs.

PMID- 9574546
TI  - The 5' untranslated region, signal peptide, and the coding sequence of the
      carboxyl terminus of IL-15 participate in its multifaceted translational control.
AB  - We previously reported that the AUG-burdened 5' untranslated region (UTR) of IL
      15 mRNA impedes its translation. Here we demonstrate that the nucleotide or
      protein sequences of the IL-15 signal peptide and carboxyl terminus also
      contribute to the poor translation of IL-15 transcripts. In particular, the
      exchange of the IL-15 signal peptide coding sequence with that of IL-2 increased
      cellular and secreted levels of IL-15 protein 15- to 20-fold in COS cells, while
      IL-2 transcripts with the IL-15 signal peptide generated 30- to 50-fold less IL-2
      protein than wild-type IL-2. Furthermore, the addition of an artificial epitope
      tag to the 3' coding sequence of IL-15 increased its protein production 5- to 10
      fold. Combining these two IL-15 message modifications, in addition to removing
      the 5' UTR, increased IL-15 synthesis 250-fold compared with a wild-type
      construct with an intact 5' UTR. These data suggest that IL-15 mRNA, unlike IL-2
      mRNA, may exist in translationally inactive pools. By storing translationally
      quiescent IL-15 mRNA, cells might respond to intracellular infections or other
      stimuli by rapidly transforming IL-15 message into one that can be efficiently
      translated.

PMID- 9574547
TI  - Selective inhibition of IL-5 receptor alpha-chain gene transcription by IL-5, IL
      3, and granulocyte-macrophage colony-stimulating factor in human blood
      eosinophils.
AB  - High affinity receptor for IL-5 (IL-5R), a predominant eosinophil maturation
      factor, is composed of an IL-5-binding alpha-chain (IL-5R alpha) and a signal
      transducing beta-chain that is shared by IL-3 and granulocyte-macrophage CSF (GM
      CSF) receptors (IL-3R and GM-CSFR). By Northern blot analysis of mRNAs obtained
      from normal human blood eosinophils, we show in this report that the
      hematopoietic cytokines IL-5, IL-3, and GM-CSF down-regulate IL-5R alpha mRNA
      while up-regulating alpha-chain mRNAs for both IL-3R and GM-CSFR as well as the
      beta-chain mRNA. More detailed characterization reveals that the down-regulation
      of IL-5R alpha mRNA is specific to IL-3, IL-5, and GM-CSF; occurs very rapidly
      (reaching maximum inhibition within 2 h); is cytokine dose dependent; and does
      not require protein synthesis. Nuclear run-on and mRNA stability experiments
      demonstrate that cytokine-induced inhibition of IL-5R alpha mRNA accumulation
      occurs at the level of IL-5R alpha gene transcription, whereas enhanced
      accumulation of mRNAs for IL-3R alpha and the beta-chain results from reduced
      mRNA degradation. We suggest from these experiments that in human blood
      eosinophils, IL-5R alpha gene transcription and IL-5R alpha mRNA metabolism can
      be regulated by mechanisms that are distinct from those used for IL-3R alpha and
      GM-CSFR alpha.

PMID- 9574549
TI  - MHC class I/peptide stability: implications for immunodominance, in vitro
      proliferation, and diversity of responding CTL.
AB  - Infection of BALB/c mice with Listeria monocytogenes primes CD8+ cytotoxic T
      cells specific for four different H2-Kd-restricted peptides. In vitro
      restimulation of L. monocytogenes immune splenocytes with each of these peptides
      resulted in larger T cell responses to p60 217-225 and mpl 84-92 than to LLO 91
      99 and p60 449-457. Direct frequency analyses of immune splenocytes, however,
      revealed that LLO 91-99 and p60 217-225 elicit dominant T cell responses, while
      p60 449-457 and mpl 84-92 elicit minor, subdominant responses. Restimulation of
      immune splenocytes with a range of peptide concentrations revealed that T cells
      with dominant specificities respond optimally to low peptide concentrations,
      while T cells specific for subdominant epitopes expand maximally to high peptide
      concentrations. This disparity correlates with the stability of H2-Kd/epitope
      complexes: the two dominant epitopes form stable complexes, while the subdominant
      epitopes form less stable complexes with H2-Kd. Interestingly, T cells specific
      for LLO 91-99 and p60 217-225 express more complex TCR-Vbeta repertoires than p60
      449-457- and mpl 84-92-specific T cells. Thus, in our system, dominant T cell
      responses have relatively diverse TCR repertoires and are specific for peptides
      that form stable complexes with MHC class I molecules. Determining the precise
      roles of epitope/MHC class I stability and TCR repertoire in the generation of
      dominant T cell responses will require further investigation.

PMID- 9574548
TI  - Transcriptional repression of the IL-2 gene in Th cells by ZEB.
AB  - Th1- and Th2-type cells mediate distinct effector functions via cytokine
      secretion in response to immunologic challenge. Precursor Th cells transcribe IFN
      gamma, IL-2, and IL-4 upon activation. Repeated stimulation of Th precursor cells
      in the presence of IL-4 leads to terminally differentiated Th2 cells that have
      lost the ability to transcribe the IL-2 gene. We provide evidence that repression
      of IL-2 gene expression in Th2 cells and partial repression in Th1 cells are
      mediated by ZEB, a zinc finger, E box-binding transcription factor. This factor
      binds to a negative regulatory element, NRE-A, in the IL-2 promoter, thereby
      acting as a potent repressor of IL-2 transcription.

PMID- 9574550
TI  - Enhancement of tumor outgrowth through CTL tolerization after peptide vaccination
      is avoided by peptide presentation on dendritic cells.
AB  - Synthetic peptide-based vaccines have been shown to induce potent protective and
      therapeutic T cell-mediated immunity in preclinical animal models and are now
      being evaluated in clinical phase I/II studies for their efficacy against tumors
      or infectious diseases. However, such vaccines might also specifically tolerize T
      cells causing enhanced tumor outgrowth, as shown by vaccination with two CTL
      epitopes derived from the adenovirus type 5 early region 1 (Ad5E1) oncogenes. We
      now report that modification of the Ad5E1 peptide vaccine either through
      incorporation of the peptides into liposomes or by ligation of the peptides to
      lipid tails, another vaccine formulation being tested in the clinic, fails to
      convert immunosuppression into effective antitumor vaccination. Inclusion of a
      helper T cell epitope into the vaccine likewise induces enhanced tumor outgrowth
      and thus does not diminish the capacity of the peptides to tolerize Ad5E1
      specific CTL. In contrast, the Ad5E1-derived peptides evoke a strong tumor
      protective CTL response when presented on dendritic cells (DC), indicating that
      the in vivo CTL-tolerizing potential of these peptides is converted to specific
      immunostimulation when presented on DC. These findings have important
      implications for the development of peptide-based immune intervention strategies
      and emphasize the superior nature of Ag-pulsed DC over other peptide-based
      vaccination protocols as well as the crucial importance of the mode of peptide-Ag
      delivery in setting the balance between T cell stimulation and tolerization.

PMID- 9574551
TI  - In situ cancer vaccination: an IL-12 defective vector/replication-competent
      herpes simplex virus combination induces local and systemic antitumor activity.
AB  - Intratumoral inoculation of replication-competent, attenuated herpes simplex
      virus (HSV) mutants inhibits tumor growth by direct cytotoxic viral replication
      and induction of a tumor-specific immune response. To boost the antitumor
      response, we describe a defective HSV vector encoding IL-12 as an adjuvant to in
      situ vaccination by the replication-competent HSV helper virus. The defective HSV
      vector system consists of defective particles containing tandem repeats of the
      cytokine genes (p40 and p35) in combination with a HSV helper virus.
      Heterodimeric IL-12 was expressed and secreted after IL-12 defective vector
      infection of tumor cells. In a syngeneic, bilateral established tumor model with
      CT26 murine colon carcinoma, unilateral intratumoral inoculation with an IL-12
      defective/replication-competent HSV vector combination significantly reduced
      tumor growth of the inoculated and noninoculated contralateral tumors. This
      antitumor effect was significantly greater than with a lacZ-defective/replication
      competent HSV vector combination, which itself was significantly greater than the
      mock inoculation. Efficacy is associated with enhancement of tumor-specific CTL
      activity, including specificity against the CT26 immunodominant MHC class I
      restricted Ag AH1, and IFN-gamma production. There was no significant tumor
      growth inhibition after intratumoral inoculation of s.c. CT26 tumors in athymic
      mice. We conclude that this defective HSV vector system is an effective method
      for cytokine gene delivery to tumors in situ and IL-12 expression in tumors
      synergizes the antitumor activity mediated by the replication-competent HSV
      helper virus.

PMID- 9574552
TI  - Repeated intratracheal instillations of nonreplicating adenovirus 2 vector
      attenuate CTL responses and IFN-gamma production.
AB  - The proposed usage of replication-deficient adenovirus (Ad) vectors for
      corrective gene therapy or for mucosal immunization has been limited in part by
      the host reactivity to the Ad vector, thus limiting repeated Ad instillations. We
      have recently shown that the reactivity to the Ad vector is in large part due to
      increased CD4+ Th1 and Th2 responses as well as elevated IgG and mucosal IgA
      responses. It has been recently proposed that the diminution of transgene
      expression in respiratory epithelia was due to increased CTL reactivity to
      expressed Ad proteins. Herein, we report that repeated intratracheal delivery of
      a second generation Ad2 vector into mice results in no detectable CTL activity in
      freshly isolated lymphoid cells from lungs, lower respiratory lymph nodes, or
      spleens or after in vitro restimulation. In contrast, a single dose of Ad2 vector
      did elicit a robust CTL response. This attenuation of CTL activity was long lived
      and was not affected by macrophage depletion or due to a reduction in CD4+ or
      CD8+ T cells. Examination of cytokine production via MHC class I or class II
      restimulation by lymphoid cells from three intratracheally treated mice showed an
      attenuation in the production of IFN-gamma by as much as 110-fold. This reduction
      in IFN-gamma could not be attributed to increased IL-4 or IL-10 production. Thus,
      this study shows that the CTL response to Ad vectors is attenuated upon repeated
      administration.

PMID- 9574553
TI  - IL-10 regulates liver pathology in acute murine Schistosomiasis mansoni but is
      not required for immune down-modulation of chronic disease.
AB  - We have used IL-10 gene knockout mice (IL-10T) to examine the role of endogenous
      IL-10 in the down-modulation of hepatic granuloma formation and lymphocyte
      responses that occurs in chronic infection with the helminth parasite Schistosoma
      mansoni. Although IL-10-deficient animals showed 20 to 30% mortality between 8
      and 14 wk postinfection, they displayed no alterations in their susceptibility to
      infection and produced similar numbers of eggs as their wild-type littermates.
      The IL-10T mice displayed a significant increase in hepatic granuloma size at the
      acute stage of infection, which was associated with increased IFN-gamma, IL-2, IL
      1beta, and TNF-alpha mRNA expression in liver and elevated Th1-type cytokine
      production by lymphoid cells. Despite developing an enhanced Th1-type cytokine
      response, the IL-10T mice showed no consistent decrease in their Th2-type
      cytokine profile. Surprisingly, although granulomatous inflammation was enhanced
      at the acute stage of infection, the livers of IL-10T mice displayed no
      significant increase in fibrosis and underwent normal immune down-modulation at
      the chronic stage of infection. Moreover, the down-modulated state could be
      induced in IL-10T mice by sensitizing the animals to schistosome eggs before
      infection, further demonstrating that the major down-regulatory mechanism is not
      dependent upon IL-10. We conclude that while IL-10 plays an important role in
      controlling acute granulomatous inflammation, it plays no essential role in the
      process of immune down-modulation in chronic schistosome infection.

PMID- 9574554
TI  - Thrombopoietin (TPO) knockout phenotype induced by cross-reactive antibodies
      against TPO following injection of mice with recombinant adenovirus encoding
      human TPO.
AB  - Adenovirus vectors have emerged as potent agents for gene transfer. Immune
      response against the vector and the encoded protein is one of the major factors
      in the transient expression following in vivo gene transfer. A single injection
      of an adenovirus encoding human thrombopoietin (TPO) into mice induced transient
      thrombocytosis, followed by a chronic immune thrombocytopenia. Thrombocytopenic
      mice had anti-human TPO Abs of the IgG2a and IgG1 isotypes. Thrombocytopenic mice
      sera neutralized more efficiently human than murine TPO, and exhibited no
      detectable anti-murine TPO Abs. Despite their low affinity for murine TPO, anti
      TPO Abs induced a TPO knockout-like phenotype, i.e., low number of marrow
      megakaryocytes and of all kinds of hemopoietic progenitors. Hybridomas derived
      from a thrombocytopenic mouse revealed cross-reactivity of all of the secreted
      anti-TPO Ab isotypes. Mice subjected to myelosuppression after virus injection
      showed that anti-human TPO of IgG1 and IgG2a isotypes disappeared. Thus,
      sustained human TPO production was responsible for platelet elevation for at
      least 5 mo. Compelling results showed that elevated IgG2a/IgG2b ratios are always
      associated with thrombocytopenia, whereas low ratios are associated with
      tolerance or normal platelet counts. Finally, we hypothesize that in humans some
      chronic thrombocytopenia associated with a low TPO plasma level are due to anti
      TPO Abs.

PMID- 9574555
TI  - Induction of in vitro human macrophage anti-Mycobacterium tuberculosis activity:
      requirement for IFN-gamma and primed lymphocytes.
AB  - Mycobacterium tuberculosis (Mtb) is the world's leading infectious cause of
      mortality. Despite the overwhelming data supporting the critical role of cellular
      immunity, little is known of the early microbial and immune cell interactions and
      whether human macrophages can be activated to express anti-Mtb activity. We
      report the reconstitution of an in vitro system whereby human macrophages express
      anti-Mtb activity only in coculture with PBL and with IFN-gamma. Omission of IFN
      gamma in the cocultures or Mtb lysate/IFN-gamma-primed lymphocytes was associated
      with high growth of Mtb, high IL-10 and IL-12 p40, nearly undetectable IL-12 p70
      levels, and the highest percentages of CD4 and CD8 T cells. In contrast, IFN
      gamma treatment of cocultures containing Mtb lysate/IFN-gamma-primed PBL reduced
      bacilli count by approximately 2.5 log, decreased the production of IL-10 by 5.7
      fold, increased IL-12 p70 by approximately 50-fold, and reduced the percentages
      of CD4 and CD8 T cells. Activation of anti-Mtb activity was time and dose
      dependent. At 2000 U/ml of IFN-gamma, bactericidal activity was achieved (10-fold
      reduction from initial inoculum). Anti-Mtb activity against several strains of M.
      tuberculosis (H37Ra and H37Rv, and C, a clinical isolate) was observed and was
      associated with expression of inducible nitric oxide synthase. These data suggest
      that induction of human macrophage anti-Mtb activity required dual signaling from
      PBL and IFN-gamma. Thus, the development of an in vitro human system may greatly
      facilitate studies to delineate immune cells, cytokines, and effector
      functions/genes critical in controlling Mtb. Defining the mechanisms may also
      provide novel treatment strategies for tuberculosis.

PMID- 9574556
TI  - Cellular mechanisms involved in protection against influenza virus infection in
      transgenic mice expressing a TCR receptor specific for class II hemagglutinin
      peptide in CD4+ and CD8+ T cells.
AB  - Mice transgenic for a TCR that recognizes peptide110-120 of hemagglutinin of PR8
      influenza virus in the context of MHC class II I-Ed molecules express the
      transgenes in both CD4+ and CD8+ T cells. We have found that these TCR
      hemagglutinin (TCR-HA) transgenic mice display a significantly increased
      resistance to the primary infection with PR8 virus compared with the wild-type
      mice. The TCR-HA transgenic mice mounted significant MHC type II and enhanced MHC
      type I-restricted cytotoxicity as well as increased cytokine responses in both
      spleen and lungs after infection with PR8 virus. In contrast, the primary humoral
      response against PR8 virus was not significantly different from that of the wild
      type mice. In vivo depletion and adoptive cell transfer experiments demonstrated
      that both CD4+ and CD8+ TCR-HA+ T cell subsets were required for the complete
      clearance of pulmonary virus following infection with a dose that is 100% lethal
      in wild-type mice. Whereas CD4+ TCR-HA+ T cells were necessary for effective
      activation and local recruitment of CD8+ T cells, CD8+ TCR-HA+ T cells showed a
      Th1-biased pattern and MHC type II-restricted cytotoxicity. However, in the
      absence of in vivo expression of MHC type I molecules on the infected cells, the
      protection conferred by the TCR-HA+ T cells was impaired, indicating that the
      enhanced MHC class I-restricted cytotoxicity due to TCR-HA+ CD4+ Th cells was a
      critical element for clearance of the pulmonary virus by the transgenic mice.

PMID- 9574557
TI  - Analysis of ligand-induced and ligand-attenuated epitopes on the leukocyte
      integrin alpha4beta1: VCAM-1, mucosal addressin cell adhesion molecule-1, and
      fibronectin induce distinct conformational changes.
AB  - The leukocyte integrin alpha4beta1 is a receptor for both cell surface ligands
      (VCAM-1 and mucosal addressin cell adhesion molecule-1 (MAdCAM-1)) and
      extracellular matrix components (fibronectin). Through regulated interactions
      with these molecules, alpha4beta1 mediates leukocyte migration from the
      vasculature at sites of inflammation. Regulation of integrin activity plays a key
      role in controlling leukocyte-adhesive events and appears to be partly determined
      by changes in integrin conformation. Several mAbs that recognize ligand-induced
      binding site epitopes on integrins have been characterized, and a subset of these
      mAbs are capable of stimulating integrin-ligand binding. Conversely, some mAbs
      recognize epitopes that are attenuated by ligand engagement and allosterically
      inhibit ligand binding. To gain insight into ligand-specific effects on integrin
      conformation, we have examined the ability of different ligands to modulate the
      binding of four distinct classes (A, B1, B2, and C) of anti-alpha4 Abs to
      alpha4beta1. VCAM-1 attenuated B (antifunctional) class epitopes via an
      allosteric mechanism and also allosterically inhibited the binding of the
      function-blocking anti-beta1 mAb 13. Additional alpha4beta1 ligands (fibronectin
      fragments, MAdCAM-1, and the CS1 peptide) also inhibited mAb 13-integrin binding;
      however, the epitopes of the class B anti-alpha4 mAbs were attenuated by the
      fibronectin fragments, but not by MAdCAM-1 or the CS1 peptide. Of the two anti
      alpha4 class A mAbs examined, one recognized an epitope that was induced uniquely
      by VCAM-1. Taken together, these data suggest that overlapping but distinct
      binding mechanisms exist for different alpha4beta1 ligands and that distinct
      conformational changes are induced upon integrin engagement by different ligands.

PMID- 9574558
TI  - Down-regulation of CXCR2 expression on human polymorphonuclear leukocytes by TNF
      alpha.
AB  - TNF-alpha is implicated in the initiation of cytokine cascades in various
      inflammatory settings. To assess the interactions of multiple cytokines at the
      level of inflammatory effector cells, we examined the effects of TNF-alpha on the
      expression of two IL-8Rs (CXCR1 and CXCR2) on polymorphonuclear leukocytes
      (PMNs). TNF-alpha decreased the surface expression of CXCR2 in a dose- and time
      dependent manner. In contrast, CXCR1 expression was not affected by TNF-alpha.
      The release of CXCR2 into the supernatant of TNF-alpha-treated PMNs was detected
      by immunoblotting and immuno-slot-blot analyses, suggesting that the down
      regulation of CXCR2 was caused mainly by shedding from the cell surface. The
      CXCR2 down-regulation was inhibited by PMSF and aprotinin, supporting the
      hypothesis that the shedding was mediated by serine protease(s). The
      intracellular Ca2+ mobilization and chemotaxis in response to IL-8 were
      suppressed by the pretreatment of PMNs with TNF-alpha, indicating that the
      decrease in CXCR2 was reflected in the decreased functional responses to IL-8. In
      contrast, the O2- release, which is mediated by CXCR1, was not suppressed by TNF
      alpha. The treatment of whole blood with TNF-alpha also caused a significant
      reduction in CXCR2 and markedly suppressed intracellular Ca2+ mobilization and
      chemotaxis in response to IL-8, while enhancing the O2- release. These findings
      suggest that TNF-alpha down-regulates CXCR2 expression on PMNs and modulates IL-8
      induced biologic responses, leading to the intravascular retention of PMNs with
      an enhanced production of reactive oxygen metabolites.

PMID- 9574559
TI  - Leukotriene B4 activates the NADPH oxidase in eosinophils by a pertussis toxin
      sensitive mechanism that is largely independent of arachidonic acid mobilization.
AB  - Experiments were designed to investigate whether leukotriene (LTB4) receptors can
      couple directly to phospholipase A2 (PLA2) in guinea pig eosinophils and the role
      of endogenous arachidonic acid (AA) in LTB4-induced activation of the NADPH
      oxidase. LTB4 (EC50 approximately 16 nM) and AA (EC50 approximately 6 microM)
      generated hydrogen peroxide (H2O2) in a concentration-dependent manner and at an
      equivalent maximum rate (5-6 nmol/min/10(6) cells). LTB4 stimulated PLA2 over a
      similar concentration range that activated the NADPH oxidase, although kinetic
      studies revealed that the release of [3H]AA (t1/2 approximately 2 s) preceded
      H2O2 generation (t1/2 > 30 s). Pretreatment of eosinophils with pertussis toxin
      abolished the increase in inositol(1,4,5)trisphosphate mass, [Ca2+]c, [3H]AA
      release, and H2O2 generation evoked by LTB4. Qualitatively identical results were
      obtained in eosinophils in which phospholipase C (PLC) was desensitized by 4beta
      phorbol 12,13-dibutyrate with the exception that [3H]AA release was largely
      unaffected. Additional studies performed with the protein kinase C inhibitor, Ro
      31-8220, and under conditions in which Ca2+ mobilization was abolished, provided
      further evidence that LTB4 released [3H]AA independently of signal molecules
      derived from the hydrolysis of phosphatidylinositol(4,5)bisphosphate by PLC.
      Pretreatment of eosinophils with the PLA2 inhibitor, mepacrine, abolished LTB4
      induced [3H]AA release at a concentration that inhibited H2O2 by only 36%.
      Collectively, the results of this study indicate that agonism of LTB4 receptors
      on guinea pig eosinophils mobilizes AA by a mechanism that does not involve the
      activation of PLC. In addition, although LTB4 effectively stimulated PLA2, a
      central role for AA in the activation of the NADPH oxidase was excluded.

PMID- 9574560
TI  - Involvement of CD14 and complement receptors CR3 and CR4 in nuclear factor-kappaB
      activation and TNF production induced by lipopolysaccharide and group B
      streptococcal cell walls.
AB  - This study was undertaken to evaluate the role of CD14 and complement receptors
      type 3 (CR3) and 4 (CR4) in mediating TNF release and NF-kappaB activation
      induced by LPS and cell wall preparations from group B streptococci type III
      (GBS). LPS and GBS caused TNF secretion from human monocytes in a CD14-dependent
      manner, and soluble CD14, LPS binding protein, or their combination potentiated
      both LPS- and GBS-induced activities. Blocking of either CD14 or CD18, the common
      beta-subunit of CR3 and CR4, decreased GBS-induced TNF release, while LPS
      mediated TNF production was inhibited by anti-CD14 mAb only. Chinese hamster
      ovary cell transfectants (CHO) that express human CD14 (CHO/CD14) responded to
      both LPS and GBS with NF-kappaB translocation, which was inhibited by anti-CD14
      mAb and enhanced by LPS binding protein. While LPS showed fast kinetics of NF
      kappaB activation in CHO/CD14 cells, a slower NF-kappaB response was induced by
      GBS. LPS also activated NF-kappaB in CHO cells transfected with either human CR3
      or CR4 cDNA, although responses were delayed and weaker than those of CHO/CD14
      cells. In contrast to LPS, GBS failed to induce NF-kappaB in CHO/CR3 or CHO/CR4
      cells. Both C3H/OuJ (Lps[n]) and C3H/HeJ (Lps[d]) mouse peritoneal macrophages
      responded to GBS with TNF production and NF-kappaB translocation, whereas LPS was
      active only in C3H/OuJ macrophages. Thus, LPS and GBS differentially involve CD14
      and CR3 or CR4 for signaling NF-kappaB activation in CHO cells and TNF release in
      human monocytes, and engage a different set of receptors and/or intracellular
      signaling pathways in mouse macrophages.

PMID- 9574561
TI  - Expression and function of the type 3 complement receptor in tissues of the
      developing mouse.
AB  - Macrophage (Mphi) expression of the leukocyte integrins has been implicated in
      their adhesion and migration in the adult. Little is known, however, of the
      expression or function of these molecules during development. This study defines
      the spatial and temporal sequences of expression of the type 3 complement
      receptor (CR3) in the developing mouse; establishes the functional efficacy of
      this molecule in spreading, adhesion, and phagocytosis; and investigates its role
      in inflammatory and constitutive migration. Expression of CR3 on monocytes
      occurred early compared to Mphi-restricted glycoprotein F4/80, but expression on
      stellate tissue Mphi appeared later than F4/80 and was transient. Expression of
      CR3 on resident tissue Mphi is more widespread during development, being retained
      on only very specific Mphi populations in the adult. Neutrophil polymorphs
      expressed CR3 from day 17 of gestation onward. The anti-CR3 mAb 5C6 was used to
      investigate the role of CR3 in adhesion, spreading, and phagocytosis by neonatal
      Mphi. Neonatal macrophages were found to adhere, spread, and phagocytose by CR3
      dependent mechanisms, and a CR3-independent system was implicated in the
      spreading of neonatal Mphi. The role of CR3 in migration during development was
      then investigated. 5C6 had potent effects on the early stages of the migration of
      myelomonocytic cells to an inflammatory stimulus in vivo. Despite efficient
      transplacental transfer of the Ab from pregnant mother to fetus, the process by
      which monocytes generate populations of resident tissue Mphi was undisrupted,
      indicating the existence of CR3-independent mechanisms of monocyte migration
      during development.

PMID- 9574562
TI  - Blockade of antibody-induced glomerulonephritis with Crry-Ig, a soluble murine
      complement inhibitor.
AB  - A recombinant soluble form of the mouse membrane complement inhibitor Crry
      (complement receptor-related gene y) fused to IgG1 hinge, CH2, and CH3 domains
      has been created and designated Crry-Ig. Crry has been used because, similar to
      human soluble CR1, it demonstrates decay-accelerating activity for both the
      classical and alternative pathways of complement as well as cofactor activity for
      factor I-mediated cleavage of C3b and C4b. The mouse IgG1 isotype was
      incorporated because it is a noncomplement-activating isotype and, when fused to
      Crry, results in a complement inhibitor that should not be recognized as foreign
      when used chronically in murine models. Crry-Ig demonstrated complement
      inhibitory activity in both the fluid phase and on target surfaces. Following in
      vivo injection, Crry-Ig manifested a two-phase serum elimination profile, a rapid
      initial loss most likely reflecting tissue redistribution and a second more
      prolonged decline with a t1/2 of 40 h. Inhibition of complement activation in
      mice following injection of Crry-Ig was demonstrated by a marked decrease in the
      ability of serum from treated mice to be activated by zymosan particles in vitro.
      Finally, in vivo efficacy of Crry-Ig was demonstrated by its ability to
      substantially diminish renal injury induced by complement-fixing nephrotoxic Ab.
      The use of Crry-Ig in vivo in murine models of chronic inflammatory and
      autoimmune disease should allow further insight into the potential therapeutic
      effects and possible untoward complications of continuous blockade of complement
      using inhibitors that act on activation products of C4 and C3.

PMID- 9574563
TI  - Regulation of human mast cell beta-tryptase: conversion of inactive monomer to
      active tetramer at acid pH.
AB  - At neutral pH, human mast cell beta-tryptase is stabilized in its enzymatically
      active, tetrameric form by heparin, and resists inhibition by biologic protease
      inhibitors. After dissociation of beta-tryptase from heparin, active tetramers
      rapidly convert to inactive monomers in an isotonic, neutral pH environment.
      Although reversible transition states probably exist during this conversion, once
      inactive monomers form, addition of heparin fails to reconstitute active tetramer
      at neutral pH. The current study shows that complete reactivation of inactive
      monomers can occur at acidic pH in a heparin-independent manner. The respective
      rate-determining steps for formation of tetramer and active enzyme from inactive
      monomers exhibit second and first order kinetics based on an analysis of initial
      reaction rates. The optimal pH for tetramer formation and reactivation is about
      6, suggesting His residues play a critical role. The optimal ionic strength
      equivalent is 160 mM NaCl; and the optimal temperature range is 22 degrees C to
      37 degrees C. We propose a sequential three-step reactivation process at acidic
      pH, dimerization of monomers (rate-determining second order step), rapid
      formation of inactive tetramers, and slow formation of active tetramers (overall
      rate-determining first order step). Whether reactivation of human beta-tryptase
      occurs at extracellular or intracellular sites, where the pH is acidic in vivo,
      should be considered.

PMID- 9574564
TI  - TNF-alpha convertase enzyme from human arthritis-affected cartilage: isolation of
      cDNA by differential display, expression of the active enzyme, and regulation of
      TNF-alpha.
AB  - A snake venom-like protease isolated by a differential display screen between
      normal and osteoarthritis (OA)-affected cartilage (designated as cSVP) has a cDNA
      sequence identical to TNF-alpha convertase enzyme (TACE). TACE shows the presence
      of an unknown prodomain, a cysteine switch, a catalytic domain, a zinc binding
      region, a disintegrin region, an EGF-like domain, a transmembrane domain, and a
      unique cytoplasmic region. A TACE construct harboring the signal + prodomain +
      catalytic region (TACE-SPCdeltaDETCy), expressed in baculovirus could cleave
      preferentially (approximately 12-fold) the TNF-specific peptide over the matrix
      metalloproteases peptide in vitro. This recombinant protein also cleaved the
      natural substrate GST-ProTNF-alpha to TNF-alpha (17 kDa) in vitro. The mRNA for
      TACE, which is broadly distributed and differentially expressed in a variety of
      human tissues, is up-regulated in arthritis-affected cartilage, but not normal
      cartilage. OA-affected cartilage also expressed TNF-alpha mRNA that was not
      detected in normal cartilage. The OA-affected cartilage (in explant assays)
      spontaneously released TNF-alpha and IL-8 in ex vivo conditions. Addition of TNF
      alphaR fused to IgG Fc fragment (TNF-alphaR:Fc) in the presence or absence of
      soluble IL-1R (with which it acted additively) significantly attenuated the
      spontaneous/autocrine release of articular IL-8 in this assay. These experiments
      demonstrate a functional paracrine/autocrine role of TNF-alpha in OA-affected
      cartilage that may depend, in part, on up-regulated levels of chondrocyte-derived
      TACE.

PMID- 9574565
TI  - Cationic lipids enhance cytokine and cell influx levels in the lung following
      administration of plasmid: cationic lipid complexes.
AB  - Administration of plasmid/lipid complexes to the lung airways may be associated,
      in addition to expression of transgene, with a range of other responses. We
      report here the induction of cytokines and cellular influx in the lung airway
      following intratracheal administration of an N-[1-(2-3-dioleyloxy)propyl]-N,N,N
      trimethylammonium chloride/cholesterol/plasmid positively charged complex in
      mice. We show that 1) the appearance of the Th1-associated cytokines IFN-gamma
      and IL-12 in bronchoalveolar lavage fluid is caused by unmethylated CpG
      dinucleotide sequences present within the plasmid, and is enhanced by the lipid
      formulation; 2) cationic lipids by themselves do not induce IL-12 or IL-12p40; 3)
      TNF-alpha is rapidly induced by cationic lipids and plasmid/lipid complex, but
      not by plasmid alone; 4) an acute cellular influx is induced by cationic lipid
      alone and by a plasmid/lipid complex, but to a much lesser extent by plasmid
      alone; and 5) plasmid methylation does not influence the degree of inflammatory
      cell influx. The induction of the innate immune responses by plasmid/lipid
      complexes may be advantageous to gene therapy of lung diseases. In particular,
      induction of the Th1 cell-promoting cytokines by plasmid/lipid complexes could,
      in conjunction with an expressed transgene, be used to modulate immune responses
      in the lung airways in disease conditions that are deficient in Th1 cell
      responses or that have a dominant Th2 phenotype. Alternatively, the elimination
      of immunostimulatory sequences in plasmids may improve the tolerability and/or
      efficacy of nonviral gene therapy, especially for diseases requiring chronic
      administration.

PMID- 9574566
TI  - Dendritic cells as the terminal stage of monocyte differentiation.
AB  - Monocytes (MO) cultured for > or =5 days with either macrophage-CSF (M-CSF) or
      granulocyte macrophage (GM)-CSF and IL-4 differentiated without concomitant
      proliferation into CD14+ macrophages (Mphi) or CD1a+ dendritic cells (DC),
      respectively. When adherent and nonadherent CD14high Mphi from M-CSF cultures
      were separated and cultured further in cytokine-free medium or with GM-CSF/IL-4,
      most cells from both fractions that were exposed to GM-CSF/IL-4 acquired CD1a
      expression and DC morphology and function. Conversely, GM-CSF/IL-4 withdrawal at
      day 5 and additional culture of sorted CD1a+ DC for 2 to 7 days in cytokine-free
      medium led to cells rapidly becoming adherent CD1a-CD14+ Mphi. Replacing GM
      CSF/IL-4 with M-CSF hastened the conversion of DC to Mphi without increasing cell
      numbers. CD1a+CD14-CD83+ mature DC were induced by a > or =2-day exposure to MO
      conditioned medium, LPS, or TNF-alpha/IL-1beta. Upon cytokine removal or culture
      with M-CSF, DC that had been pushed to maturation by conditioned medium or LPS
      remained stable or died in the new environment. TNF-alpha/IL-1beta-driven DC
      displayed heterogeneous CD83 expression and could thus be sorted into CD83high
      and CD83low/- cells; in cytokine-free medium or in M-CSF, most CD83low/- cells
      converted to Mphi, whereas most CD83high cells remained nonadherent CD1a+CD14- or
      died and thus appeared truly terminally differentiated. Hence, MO are precursors
      of Mphi as well as of DC, with each cell type having the capability to convert
      into the other until late in the differentiation/maturation process. Accordingly,
      the cytokine environment and the presence of differentiation and/or other
      stimulatory signals may be the "final decision-making factors" determining
      whether these cells will acquire DC or Mphi characteristics and function.

PMID- 9574567
TI  - Inducible expression of the alpha1-acid glycoprotein by rat and human type II
      alveolar epithelial cells.
AB  - Alpha1-acid glycoprotein (AGP) is a major acute phase protein in rat and human.
      AGP has important immunomodulatory functions that are potentially important for
      pulmonary inflammatory response. The liver is the main tissue for AGP synthesis
      in the organism, but the expression of AGP in the rat lung has not been
      investigated. We show that AGP mRNA was induced in the lung of dexamethasone-,
      turpentine-, or LPS-treated rats, whereas AGP mRNA was not detected in the lung
      of control rats. In the lung of animals treated intratracheally with LPS, in situ
      hybridization showed that AGP gene expression was restricted to cells located in
      the corners of the alveolus, consistent with an alveolar type II (ATII) cell
      localization. The inducible expression of the AGP gene was confirmed in vitro
      with SV40 T2 cells and rat ATII cells in primary culture: maximal expression
      required the presence of dexamethasone. IL-1 and the conditioned medium of
      alveolar macrophages acted synergistically with dexamethasone. Rat ATII cells
      secreted immunoreactive AGP in vitro when stimulated with dexamethasone or with a
      combination of dexamethasone and the conditioned medium of alveolar macrophages.
      In vivo, in the human lung, we detected immunoreactive AGP in hyperplastic ATII
      cells, whereas we did not detect AGP in the normal lung. We conclude that AGP is
      expressed in the lung in cases of inflammation and that ATII cells are the main
      source of AGP in the lung.

PMID- 9574568
TI  - Monocyte chemoattractant protein-1 synthesis by murine lung fibroblasts modulates
      CD4+ T cell activation.
AB  - This study addressed the role of endogenous monocyte chemoattractant protein-1
      (MCP-1) in Ag-stimulated lymphokine synthesis and proliferation by CD4+ T cells
      during their coculture with purified lung fibroblasts or splenic macrophages.
      Initial experiments showed that fibroblasts exposed to IL-4, TNF alpha, or IL-4
      and TNF-alpha (all at 10 ng/ml) for 24 h released five- to eightfold more MCP-1
      than similarly treated splenic macrophages. In 72-h coculture experiments, the
      synthesis of IL-4 by OVA-activated CD4+ T cells added to lung fibroblasts or
      splenic macrophages was significantly inhibited when endogenous MCP-1 was
      neutralized using polyclonal anti-MCP-1 antiserum. In these same cocultures, IFN
      gamma levels were significantly enhanced. Similarly, IFN-gamma levels were
      significantly enhanced in 72-h cocultures of a purified peptide derivative
      activated CD4+ Th1 clone and lung fibroblasts or splenic macrophages following
      immunoneutralization of MCP-1. In separate experiments, the selective inhibition
      of MCP-1 synthesis by lung fibroblasts and splenic macrophages using an MCP-1
      antisense oligonucleotide significantly enhanced the proliferation of CD4+ T
      cells during a 96-h coculture. Taken together, these data suggest that MCP-1
      exerts an immunomodulatory effect on CD4+ T cell-derived IL-4 and IFN-gamma
      release and CD4+ T cell proliferation during cell-to-cell interactions.

PMID- 9574569
TI  - Transient gene transfer of IL-12 regulates chemokine expression and disease
      severity in experimental arthritis.
AB  - Murine collagen-induced arthritis (CIA) is characterized by pannus formation,
      cell infiltration, and cartilage erosion, and shares histologic and immunologic
      features with rheumatoid arthritis. Numerous cytokines are reportedly associated
      with RA and/or CIA; however, their mechanistic role is not clear. To determine
      the role of IL-12 in CIA, DBA/1 LacJ mice were administered 3 x 10(8) plaque
      forming units of mIL-12 i.p. in a nonreplicating adenoviral vector (AdIL-12) on
      day 25 following primary type II collagen immunization. Our studies demonstrated
      that systemic transient overexpression of IL-12 accelerated disease progression
      and augmented the arthritis severity relative to mice expressing a replication
      deficient, E1-deleted Ad5 construct. A likely mechanism for this increase in
      pathology was the increase in the expression of cytokines and chemokines known to
      play a proinflammatory role in disease. In particular, levels of murine IFN-gamma
      were significantly increased in mice overexpressing AdIL-12 relative to the
      replication-deficient, E1-deleted Ad5 construct. Interestingly, the C-X-C
      chemokine murine macrophage inflammatory protein-2, as well as the C-C chemokines
      murine monocyte chemoattractant protein-1 and murine macrophage inflammatory
      protein-1alpha were up-regulated by AdIL-12 relative to controls. In an
      additional set of studies, neutralization of endogenous IL-12 in CIA mice was
      shown to delay disease onset and attenuate disease severity. IFN-gamma levels in
      the mice receiving anti-IL-12 were significantly decreased in joint homogenates.
      These studies demonstrate that IL-12 is an important cytokine involved in
      controlling the production of chemokines/cytokines leading to the evolution of
      experimental arthritis.

PMID- 9574570
TI  - Enhanced expression of B7.2 (CD86) in patients with atopic dermatitis: a
      potential role in the modulation of IgE synthesis.
AB  - Recent studies have suggested that the accessory molecules B7.1 (CD80) and B7.2
      (CD86) differ in their capacity to generate Th1 vs Th2 responses. Atopic
      dermatitis (AD) is a chronic allergic skin disease associated with increased IgE
      synthesis. To determine the potential role of B7.2 molecules in AD, the present
      study was conducted to compare the expression of B7.1 vs B7.2 on B cells from
      patients with AD vs normal subjects or patients with psoriasis. The expression of
      B7.2 on B cells of AD patients (53.67 +/- 3.10%) was significantly higher than
      normals (38.02 +/- 4.95%; p = 0.02) and psoriasis patients (40.19 +/- 2.70%; p =
      0.006). In contrast, there was no significant difference in B7.1 expression among
      the three subject groups. Interestingly, total serum IgE from AD patients and
      normal subjects correlated significantly with B7.2 expression on B cells (r =
      0.68; p = 0.004), suggesting a role for B7.2+ B cells in IgE synthesis. Indeed,
      purified B7.2+ B cells produced significantly more IgE than B7.2- B cells in
      vitro (p = 0.04). Anti-human B7.2, but not B7.1, mAb significantly (p < 0.05)
      decreased IgE production by PBMC stimulated with IL-4 and anti-CD40 mAb.
      Furthermore, B7.2+ B cells had a significantly higher level of IL-4R and CD23
      expression than B7.1+ B cells. These data demonstrate the predominant expression
      of B7.2 in AD, but not psoriasis, and a novel role for this molecule in IgE
      synthesis.

PMID- 9574571
TI  - An immunodominant epitope from mycobacterial 65-kDa heat shock protein protects
      against pristane-induced arthritis.
AB  - Previous studies showed that mice with pristane-induced arthritis (PIA) and those
      protected from the disease by preimmunization with mycobacterial 65-kDa heat
      shock protein (hsp65) possess raised immune responses to hsp65. Additionally, T
      cells from hsp65-protected mice, but not from pristane-injected or normal mice,
      produced the Th2-associated cytokines IL-4, IL-5, and IL-10 in response to
      stimulation with hsp65. Here we demonstrate that the specificity of the immune
      response to hsp65 and related heat shock protein (hsps) differs between protected
      and PIA mice. T cells from hsp65-protected mice respond to the bacterial hsps
      tested but not to the mammalian homologue, hsp58. Similarly, they exhibit high
      serum titers of anti-hsp65 Abs, yet they have virtually undetectable levels of
      anti-hsp58 IgG. By contrast, both cellular and humoral immune responses are
      detectable to bacterial and mammalian hsps in mice with PIA. An immunodominant T
      cell epitope has been identified in hsp65-protected mice corresponding to amino
      acids 261-271 from hsp65. Immunization of mice, either before or after the
      induction of arthritis, with this bacterial peptide, but not its mammalian
      homologue, protects mice from the development of PIA, and protection is
      associated with the production of Th2-type cytokines. Other experiments revealed
      that T cells primed with bacterial 261-271 or the mammalian homologue do not
      cross-react at the proliferative or cytokine level. These results demonstrate
      that an hsp65 peptide-specific Th2 response confers protection from PIA but do
      not support the idea that protection is mediated by a cross-reaction with self
      hsp58 in the joints.

PMID- 9574572
TI  - Dystrophin acts as a transplantation rejection antigen in dystrophin-deficient
      mice: implication for gene therapy.
AB  - Duchenne muscular dystrophy is a lethal and common X-linked recessive disease
      caused by a defect in dystrophin. Normal myoblast transplantation and dystrophin
      gene transfer have been expected to correct the deficiency in the muscles, but
      their clinical application has been hampered by the limited preservation of
      dystrophin-positive myofibers. In this study we investigated the mechanism for
      immunologic rejection of normal C57BL/10 (B10) myoblasts transplanted into
      dystrophin-deficient mdx mice, an animal model of Duchenne muscular dystrophy. We
      found that mdx mice develop CTL specific for dystrophin itself, which were CD8
      dominant and restricted by H-2Kb. We identified several antigenic peptides
      derived from dystrophin that bind to H-2Kb and are recognized by the mdx anti-B10
      CTL. Immunologic tolerance against dystrophin was successfully induced by i.v.
      injection of these peptides before B10 myoblast transplantation, which resulted
      in sustained preservation of dystrophin-expressing myofibers in mdx mice. These
      results demonstrate that dystrophin is antigenic in dystrophin-deficient mice and
      that immunologic regimen would be necessary to achieve the persistent expression
      of introduced dystrophin in the muscles of dystrophin-deficient individuals.

PMID- 9574573
TI  - In vitro stimulation of C1s proteolytic activities by C1s-presenting
      autoantibodies from patients with systemic lupus erythematosus.
AB  - Anti-C1s autoantibodies (IgG forms), which recognize the conjunction of C1s heavy
      chain and light chain (C1s-presenting autoantibodies) from patients with systemic
      lupus erythematosus (SLE), have been found to stimulate C1s enzymatic activities.
      This is due to acceleration of the proteolytic hydrolysis of the synthetic
      substrate C1-1 by C1s, enhancement of the complex formation of C1s with its
      natural pseudosubstrate, C1 inhibitor (C1 inh), and promotion of proteolytic
      activation of its natural substrate, C4. Seven of fifteen samples from patients
      with SLE were found to contain such autoantibodies. The hydrolysis of the
      synthetic substrate C1-1 catalyzed by C1s in 25 to 27 min in the presence of anti
      C1s autoantibodies was equivalent to the hydrolysis of C1-1 catalyzed by C1s
      alone or C1s with control IgG from healthy sera in 110 min, approximately
      fourfold faster than the reaction in the absence of anti-C1s autoantibodies.
      Densitometry scanning data showed that the formation of the C1s-C1 inh complex in
      the presence of anti-C1s autoantibodies was three to four times greater than that
      with control IgG. It was also noticed that the autoantibodies convert almost all
      of the latent forms of C1s to an active form that binds to C1 inh. Another group
      of Western blots showed that C1s cleaved C4 alpha-chain three times faster in the
      presence of autoantibodies than of control IgG. It is likely that the
      overconsumption of complement components is common in the pathogenesis of tissue
      damage occurring in SLE.

PMID- 9574574
TI  - "On the AJR viewbox": whatever happened to great cases?

PMID- 9574575
TI  - Radiology report times: impact of picture archiving and communication systems.
AB  - OBJECTIVE: We investigated the impact on radiologist reporting time of the change
      from conventional film to hard-copy computerized radiography and of the
      subsequent move to soft-copy images on picture archiving and communication system
      (PACS) workstations. MATERIALS AND METHODS: A controlled before and after
      research design was undertaken. Data were collected on four occasions: two
      relating to conventional film, one relating to hard-copy computerized
      radiography, and one relating to soft-copy PACS images. Data collection was by
      direct observation of radiology reporting sessions by independent health service
      researchers. Data were collected on report times, details of images viewed,
      characteristics of the radiologist, and details of interruptions. To control for
      potential biases in the before and after comparisons, ordinary least squares
      multiple regression analysis was used. The principal comparison was between
      reports with PACS and reports with computerized radiography hard-copy because no
      change was noted in the organization of the reporting process between these two
      data collection rounds other than the introduction of the PACS. RESULTS: Data
      were collected on a total of 5568 report observations. Report time in the PACS
      data collection period was not significantly different (p = .32) than that in the
      computerized radiography hard-copy period. Reporting with the PACS was associated
      with significantly more (p < .01) historical images (i.e., images of the same
      patient obtained in previous examinations) being viewed. CONCLUSION: Report time
      was not lengthened by the introduction of the PACS. The finding that more
      historical images were viewed when the PACS was in use indicates that the PACS
      brought about a positive change in reporting practice.

PMID- 9574576
TI  - Reducing the intussuscepted colon.

PMID- 9574577
TI  - Web-based digital radiology teaching file: facilitating case input at time of
      interpretation.
AB  - OBJECTIVE: Our goal was to develop a software system that allows easy and rapid
      input of digital radiology images and text reports, at the time of
      interpretation, into an easily searchable electronic teaching file database using
      the Internet and the World-Wide Web protocols, servers, and browsers. CONCLUSION:
      Using the Internet, the World-Wide Web, and our software system, we can rapidly
      input digital radiology images and associated text reports into an easily
      searchable database accessed by privileged users. This inexpensive and simple
      method for building a digital teaching file database allows cross-platform access
      for users who have a Web browser.

PMID- 9574578
TI  - A primer on patient management problems in interventional radiology.

PMID- 9574579
TI  - Mechanical thrombolysis of acute occlusion of both the superficial and the deep
      femoral arteries using a thrombectomy device.
AB  - OBJECTIVE: Our objective was to evaluate the efficacy of the Amplatz thrombectomy
      device for recanalization of acute occlusions of both the superficial and the
      deep femoral arteries. MATERIALS AND METHODS: Eighteen patients with acute
      occlusions of the femoral arteries (eight male, 10 female; 10-87 years old) were
      treated using the Amplatz thrombectomy clot macerator. The duration of occlusion
      was 16 +/- 8 hr. Eighteen patients underwent treatment of the deep femoral
      artery, and 16 patients had additional involvement of the superficial femoral
      artery. After primary recanalization of the deep femoral artery, the superficial
      femoral artery was also recanalized using the Amplatz thrombectomy device. Nine
      patients required additional aspiration thrombectomy of the tibial arteries, five
      patients required additional aspiration thrombectomy of side branches of the deep
      femoral artery, and 12 patients required additional local thrombolysis with
      urokinase. RESULTS: In 14 (78%) of 18 patients, recanalization of the deep
      femoral artery was complete without demonstrable residual thrombi. Arterial
      spasms were observed in five patients (28%). The rate of limb salvage was 94% at
      a mean follow-up interval of 8.9 +/- 4.1 months. In the 18 patients, the ankle
      brachial pressure index went from a median value of 0.56 before therapy to a
      median value of 0.91 after therapy. No severe complications occurred. CONCLUSION:
      Mechanical thrombolysis in the deep femoral artery with the Amplatz thrombectomy
      device is an effective, rapid method of treatment and is rarely associated with
      complications. In cases of concomitant occlusion of the tibial arteries,
      recanalization should always be attempted because the deep femoral artery may
      provide a functionally decisive collateral artery between the iliac and tibial
      vasculature.

PMID- 9574580
TI  - Restenosis of peripheral stents and stent grafts as revealed by intravascular
      sonography: in vivo comparison with angiography.
AB  - OBJECTIVE: Our objective was to compare intravascular sonography with digital
      subtraction angiography (DSA) in the assessment of luminal dimension and
      morphologic features of endovascular stents and stent grafts. MATERIALS AND
      METHODS: Thirty-seven pelvic and 24 femoral stents (12 Wall-stents; 27 covered
      and 22 uncovered nitinol stents) in 50 patients were evaluated 15 +/- 10 months
      after implantation by DSA and intravascular sonography. The degree of maximum
      instent restenosis as revealed by DSA and intravascular sonography was compared
      for each location. Morphologic features of the stents and stenoses were also
      assessed. RESULTS: Intravascular sonography and DSA correlated well (R2 = .96) in
      determining in-stent restenosis. In-stent restenosis was underestimated by 13% +/
      6% by DSA compared with intravascular sonography. Differences in determining in
      stent restenosis with intravascular sonography and DSA were not associated with
      severity of stenosis or type of stent. Intravascular sonography revealed
      incomplete expansion of stents in 21 cases, whereas DSA revealed incomplete
      expansion of stents in seven cases. The intra- and interobserver variabilities in
      our study were 4% and 5%, respectively. CONCLUSION: In-stent restenoses are
      underestimated with DSA. Intravascular sonography is superior to DSA for
      detection of incomplete stent expansion.

PMID- 9574581
TI  - Temporary splenic artery balloon occlusion for protection of nonsplenic vascular
      beds during splenic embolization.

PMID- 9574582
TI  - Use of the transgluteal route for percutaneous abscess drainage in acute
      diverticulitis to facilitate delayed surgical repair.

PMID- 9574583
TI  - Radiologic placement of long-term hemodialysis catheters in occluded jugular or
      subclavian veins or through patent thyrocervical collateral veins.

PMID- 9574584
TI  - One-step needle aspiration and lavage for the treatment of abdominal and pelvic
      abscesses.
AB  - OBJECTIVE: This retrospective study was undertaken to show the efficacy and
      safety of one-step needle aspiration and lavage for the treatment of nonenteric,
      nonpancreatic abdominal and pelvic abscesses. MATERIALS AND METHODS: Eighty-two
      nonconsecutive patients (age range, 4-81 years old) with 97 abdominal and pelvic
      abscesses were treated over 16 years with a one-step percutaneous needle
      aspiration and lavage technique. Abscesses were drained with sonographic or CT
      guidance in a single session. An 18-gauge needle was used for aspiration and
      repeated saline lavage; no drainage catheter was left in place. For collections
      that appeared multiloculated, needle repositioning and repeated aspiration and
      lavage were performed during the single session. All patients received i.v.
      antibiotics. RESULTS: Eighty-seven (90%) of 97 abscesses in 72 of 82 patients
      were successfully treated, including 17 (85%) of 20 abscesses that were
      multiloculated. The only two complications were transient sepsis in one patient
      and hemorrhage in one patient that resolved with transfusion and conservative
      treatment. Needle aspiration and lavage failures were associated with diffuse
      peritonitis, occult malignancy, unsuspected enteric communication, and a dropped
      surgical clip. CONCLUSION: Percutaneous needle aspiration and lavage can be a
      safe, effective alternative to the more conventional treatment of prolonged
      catheter drainage. In selected patients, including certain patients with
      multiloculated abscesses, one-step needle aspiration and lavage should be
      considered as the initial method of treatment.

PMID- 9574585
TI  - Arterioportal fistula due to a ruptured pancreatic pseudocyst: diagnosis and
      endovascular treatment.

PMID- 9574586
TI  - MR imaging of knees having isolated and combined ligament injuries.
AB  - OBJECTIVE: Although clinical evaluation and MR imaging both accurately reveal
      injuries in knees with isolated ligament tears, physical examination becomes
      progressively less reliable when multiple lesions exist. We investigated the
      accuracy of MR imaging of knees having varying degrees and numbers of ligament
      injuries. SUBJECTS AND METHODS: We prospectively interpreted the MR images of 340
      consecutive injured knees and compared these interpretations with the results of
      subsequent arthroscopy or open surgery, which served as the gold standard. Our
      interpretations of MR images focused on five soft-tissue supporting structures
      (the two cruciate ligaments, the two collateral ligaments, and the patellar
      tendon) and the two menisci. Patients were divided into three groups: no ligament
      injuries, single ligament injuries, and multiple ligament injuries. RESULTS:
      Using MR imaging, we found overall sensitivity and specificity for diagnosing
      ligament tears to be 94% and 99%, respectively, when no or one ligament was torn
      and 88% and 84%, respectively, when two or more supporting structures were torn.
      The difference in specificity was statistically significant (p < .0001).
      Sensitivity for diagnosing meniscal tears decreased as the number of injured
      structures increased, but the relationship achieved statistical significance (p =
      .001) only for the medial meniscus. For all categories of injury, MR imaging was
      more accurate than clinical evaluation, statistics for which were taken from the
      orthopedic literature. CONCLUSION: In knees with multiple ligament injuries, the
      diagnostic specificity of MR imaging for ligament tears decreases, as does the
      sensitivity for medial meniscal tears.

PMID- 9574587
TI  - Anterior cruciate ligament injury: fast spin-echo MR imaging with arthroscopic
      correlation in 217 examinations.
AB  - OBJECTIVE: Our objective was to evaluate the accuracy of MR imaging strategy that
      uses primarily fast spin-echo sequences for the diagnosis of anterior cruciate
      ligament tears. MATERIALS AND METHODS: The original clinical interpretations of
      MR images of 217 examinations of the knee joint were correlated with subsequent
      arthroscopic results. Each MR examination included a double-echo fast spin-echo
      sequence as the only imaging sequence in the sagittal plane. Subsequent
      discordant MR and arthroscopic examinations were then subjected to reanalysis by
      two observers who were unaware of arthroscopic results to determine if
      misinterpretations were observer or image dependent. Two hundred sixteen patients
      who underwent MR imaging for suspected internal derangement of the knee
      subsequently underwent arthroscopic surgery. Two patients had both knees
      evaluated. One patient was excluded because he was referred for evaluation for
      osteomyelitis, not internal derangement. This yielded a total number of 217 MR
      examinations for suspected internal derangement of the knee. RESULTS: For 56
      arthroscopically proven tears, the sensitivity of MR imaging was 96%. The
      specificity was 98%, yielding an overall accuracy rate of 98%. The positive and
      negative predictive values were 95% and 99%, respectively. These values are
      within the ranges of previously reported MR imaging strategies using conventional
      spin-echo sequences. CONCLUSION: Fast spin-echo MR imaging of the knee can be an
      alternative to conventional spin-echo imaging for the detection of anterior
      cruciate ligament tears.

PMID- 9574588
TI  - An easy linear estimation of the mechanical axis on long-leg radiographs.

PMID- 9574589
TI  - MR imaging of articular cartilage of the knee: new methods using ultrashort TEs.

PMID- 9574590
TI  - Usefulness of MR imaging in the detection of talar dome injuries.
AB  - OBJECTIVE: Patients with significant ankle injuries often have normal findings on
      conventional radiographs despite severe ligament, tendon, and bone injuries. MR
      imaging was used to assess the incidence of talar dome injuries in patients who
      had failed conservative therapy after ankle trauma. SUBJECTS AND METHODS: MR
      images were obtained in 30 patients with persistent ankle pain 6 weeks after an
      injury. All patients had normal findings on conventional radiographs. Patients
      with clinical symptoms suggesting ligamentous instability were excluded from the
      study. Simplified MR sequences using coronal T1-weighted and short inversion time
      inversion recovery images were used. Total scan time for each patient was 11 min.
      RESULTS: On MR imaging, 17 (57%) of 30 patients had injuries at the talar dome
      despite normal findings on conventional radiographs. Early detection resulted in
      cessation of physical therapy and casting of the ankle for 4 weeks. Ten of the
      patients with abnormalities on MR imaging underwent follow-up MR imaging within 1
      year of first MR imaging, with resolution of the previously noted abnormalities.
      The 13 patients with normal findings on MR images 6 weeks after injury continued
      with physical therapy with subsequent resolution of their pain. CONCLUSION:
      Limited MR images of the ankle are useful for detecting talar dome injuries. A
      significant incidence (57%) of talar dome injury occurred despite normal findings
      on conventional radiographs in patients with persistent ankle pain.

PMID- 9574591
TI  - Detection of ankle effusions: comparison study in cadavers using radiography,
      sonography, and MR imaging.
AB  - OBJECTIVE: The purpose of this study was to compare radiography, sonography, and
      MR imaging in revealing ankle effusions in cadaveric specimens. MATERIALS AND
      METHODS: Known quantities of saline solution were instilled in increments into
      the ankle joints of three cadaveric specimens. Imaging was completed after each
      injection with the ankle in dorsiflexion, plantar flexion, and a neutral
      position. Imaging included radiography, sonography, and MR imaging. Three
      observers who were aware of possible joint fluid evaluated the images by
      consensus and determined the presence or absence of joint effusion. RESULTS: MR
      imaging revealed 1 ml of fluid within the anterior recess of the ankle in a
      neutral position and in plantar flexion and within the posterior recess in
      dorsiflexion. Sonography revealed 2 ml of fluid within the anterior recess in a
      neutral position and in plantar flexion. Radiography revealed 5 ml of fluid
      within the anterior recess in a neutral position. CONCLUSION: MR imaging,
      sonography, and lateral radiography, in order of decreasing sensitivity, revealed
      ankle effusion. The power to reveal with each technique is influenced by the
      precise position of the ankle.

PMID- 9574592
TI  - MR imaging of the normal and abnormal retrocalcaneal bursae.
AB  - OBJECTIVE: The aim of this study was to define the MR imaging criteria for normal
      and abnormal retrocalcaneal bursae. SUBJECTS AND METHODS: Fifty ankles in 25
      asymptomatic volunteers and 30 ankles in patients with Achilles tendon disorders
      underwent MR imaging. Increased signal intensity consistent with fluid or
      synovium outlining the retrocalcaneal bursa was measured. RESULTS: Of 80 bursae,
      77 (96%) had measurable fluid or synovial signal intensity revealed by MR
      imaging. Asymptomatic volunteers had average bursal dimensions of 1 mm in the
      anteroposterior dimension, 6 mm in the transverse dimension, and 3 mm in the
      craniocaudal dimension. Bursal dimensions greater than 1 mm, 11 mm, or 7 mm,
      respectively, were not seen in asymptomatic subjects but were seen in 16 (53%) of
      30 ankles of patients with Achilles tendon disorders. CONCLUSION: On MR imaging,
      the asymptomatic retrocalcaneal bursa normally contains detectable high-signal
      intensity fluid or synovium or both. A bursa larger than 1 mm anteroposteriorly,
      11 mm transversely, or 7 mm craniocaudally is abnormal.

PMID- 9574593
TI  - Myxoid liposarcoma of the thigh.

PMID- 9574594
TI  - MR imaging of primary lymphoma of bone: variability of T2-weighted signal
      intensity.
AB  - OBJECTIVE: The purpose of this study was to investigate the MR imaging
      characteristics of primary lymphoma of bone. MATERIALS AND METHODS: Records of 27
      patients with histologic and clinical evidence of primary lymphoma of bone were
      retrospectively reviewed. Nineteen of these patients underwent MR imaging before
      surgical biopsy and initiation of therapy. Fifteen of the 19 patients underwent
      conventional spin-echo T1- and T2-weighted imaging, and the other four patients
      underwent T1-weighted and fast spin-echo T2-weighted imaging with fat saturation.
      MR images were separately and independently reviewed by two observers for signal
      intensity characteristics and homogeneity on T1- and T2-weighted sequences.
      Signal intensity characteristics were correlated with semiquantitative
      histopathologic assessments of tumor fibrosis, maturity of fibrosis, and
      vascularity. RESULTS: T1-weighted signal intensity ranged from isointense to
      hypointense relative to muscle for all lesions. Twelve of 19 cases showed
      heterogeneity of signal intensity on T2-weighted images. Predominant tumor T2
      weighted signal intensities relative to fat for the 19 patients were assessed as
      hypointense (observer 1, n = 3; observer 2, n = 1), isointense (observer 1, n =
      10; observer 2, n = 11), and hyperintense (observer 1, n = 6; observer 2, n = 7).
      No correlation among intralesional fibrosis, maturity of fibrosis, or
      intralesional vascularity and T2-weighted signal intensity characteristics was
      found. CONCLUSION: T2-weighted MR imaging characteristics of primary lymphoma of
      bone vary and do not seem to be a simple reflection of histologic findings of
      intralesional vascularity or fibrosis.

PMID- 9574595
TI  - Late diagnosis of oxalosis in an adult patient: findings on bone radiography.

PMID- 9574596
TI  - Differentiation of benign from malignant musculoskeletal lesions using MR
      imaging: pitfalls in MR evaluation of lesions with a cystic appearance.

PMID- 9574597
TI  - Acute plastic bowing deformation of the forearm in an adult.

PMID- 9574598
TI  - Excretory phase CT urography for opacification of the urinary collecting system.
AB  - OBJECTIVE: The purpose of our study was threefold: to evaluate the ability of
      excretory phase CT urography to opacify the urinary collecting system by
      comparing opacification seen on CT with the opacification seen on a series of
      unmatched IV urography examinations; to determine the optimal CT urography
      technique for ureteral filling by comparing studies of patients who were imaged
      supine, prone, and with abdominal compression; and to assess the possible value
      that reformatted planar images might add to axial excretory phase images.
      SUBJECTS AND METHODS: Seventy patients with hematuria were imaged in one of four
      ways. Twenty-five patients underwent contrast-enhanced excretory phase helical CT
      of the kidneys, ureters, and bladder. All patients were imaged in a supine
      position. Ten other patients underwent a similar CT protocol in which we used
      abdominal compression. Ten further patients underwent excretory phase CT while in
      a prone position. A final 25 patients underwent IV urography. Each patient's
      collecting system was arbitrarily divided into 10 parts (both right and left
      sides of calices; pelvis; upper, mid, and lower ureters) for scoring of images on
      a five-point scale for opacification by contrast material. Opacification scores
      for the four groups of patients were then compared. For patients who underwent
      CT, reformatted images of the collecting systems were generated and evaluated for
      their potential to add value to the conventional axial images. RESULTS: We found
      no significant difference in the ability of CT urography and IV urography to
      yield opacification of the calices, pelvis, and upper or mid ureters.
      Opacification of the distal ureter was less well seen on supine CT urography than
      on IV urography. Prone and compression CT urography resulted in better
      opacification of the collecting system than the supine noncompression technique.
      Opacification of the distal ureter was best seen with compression CT and was as
      good as that seen with IV urography. Reformatted CT urography was judged to be of
      probable or definite additional value to the axial images in 44% of cases. In
      each case, we saw a pathologic finding whose relationship to the kidney and
      collecting system was not as easy to appreciate on the axial CT scans.
      CONCLUSION: CT urography with abdominal compression results in reliable
      opacification of the collecting system that is comparable with opacification seen
      on IV urography. In patients with abnormalities, reformatted images were a useful
      adjunct to axial images. CT urography has potential as an imaging tool for the
      urothelium.

PMID- 9574599
TI  - Sonography of the female urethra.
AB  - OBJECTIVE: The purpose of this study was to explore the role of sonography for
      women with urethral symptoms and a suspected urethral diverticulum. SUBJECTS AND
      METHODS: Nineteen women with urethral symptoms underwent voiding
      cystourethrography (VCUG) and transvaginal, transperineal, and urethral
      sonography (using a catheter-based transducer). VCUGs and sonograms were
      evaluated for diverticula, defined on sonography by direct visualization of the
      neck connecting the periurethral sac with the urethral lumen. The diverticular
      neck, size, location, and shape were noted. Lesions revealed by sonography as not
      connected to the urethra were also noted. RESULTS: Of 19 women, 14 had urethral
      diverticula and one had two diverticula, for a total of 15 diverticula. On
      sonography the diverticula ranged in diameter from 2 mm to 5 cm. Both sonography
      and VCUG showed 13 of the 15 diverticula. In addition, sonography revealed two
      infected periurethral cysts, a periurethral leiomyoma, a diffuse urethritis, and
      scarring or deformity of one patient's urethra from a prior diverticulectomy. On
      sonography, eight of the 13 diverticula wrapped around more than 50% of the
      urethral circumference. The neck was precisely seen (by definition) in 13 of 15
      diverticula on sonography and in two of 13 diverticula on VCUG. CONCLUSION:
      Sonography is useful in this group of women with urethral symptoms and suspected
      urethral diverticula. It provides information on the extent and location of the
      diverticular neck, both of which are important in surgical excision. Also,
      sonography provides information on lesions not connected to the urethra.
      Sonography may prove useful in a broader group of women with urethral
      symptomatology.

PMID- 9574601
TI  - Localized in vivo 1H nuclear MR spectroscopy for evaluation of human uterine
      cervical carcinoma.

PMID- 9574600
TI  - Placement of retrograde nephroureteral stents through ileal conduits.
AB  - OBJECTIVE: Our objective was to evaluate retrograde nephroureteral stent
      placement in patients with ileal conduits. CONCLUSION: In patients with ureteral
      complications after cystectomy and ileal diversion, retrograde nephroureteral
      stent placement should be the treatment of choice to reduce patient morbidity,
      increase patient comfort, and facilitate stent care.

PMID- 9574602
TI  - CT of the ureteral wall.

PMID- 9574603
TI  - Renal artery entrapment by the diaphragmatic crus revealed by helical CT
      angiography.

PMID- 9574604
TI  - Retrocrural loop of the ureter: CT findings.

PMID- 9574605
TI  - Sonographic evaluation of the placental cord insertion site.
AB  - OBJECTIVE: Velamentous and marginal umbilical cords are uncommon abnormalities of
      placental cord insertion that can entail significant fetal risk. We undertook
      this investigation to assess the ability of prenatal sonography to reveal
      abnormal insertions of the umbilical cord into the placenta. SUBJECTS AND
      METHODS: Forty-six patients had both prenatal sonographic evaluation of the
      placental cord insertion site and postnatal pathologic examination. Distance from
      the insertion site to the nearest placental edge was categorized by sonography
      and pathology as normal if greater than 1 cm and abnormal if less than or equal
      to 1 cm. Sonographic and pathologic findings were compared. RESULTS: Thirty-eight
      singleton and eight twin pregnancies, for a total of 54 cord insertions, were
      studied. Of the 43 sonographically normal insertions, 38 had normal pathologic
      findings, and the remaining five insertions had abnormal pathologic findings (all
      marginal cord insertions). All 11 insertions that showed abnormality on
      sonography were abnormal on pathologic examination (seven marginal and four
      velamentous insertions). Sonography was able to reveal a difference between the
      two types of abnormal insertions in only a single patient, in whom the cord
      insertion changed from marginal to velamentous during a 7-week interval.
      Sonography had an overall sensitivity of 69% (11/16), a specificity of 100%
      (38/38), and an accuracy of 91% (49/54) for revealing abnormal placental cord
      insertion sites. CONCLUSION: Targeted sonographic examination of the placental
      site of umbilical cord insertion will reveal abnormal placental cord insertions,
      although distinguishing the specific type of abnormal insertion may require the
      use of color Doppler imaging.

PMID- 9574606
TI  - Sonographic detection of echogenic fluid and correlation with culdocentesis in
      the evaluation of ectopic pregnancy.
AB  - OBJECTIVE: Because the presence of echogenic fluid on transvaginal sonography has
      been shown to correlate well with hemoperitoneum in patients with possible
      ectopic pregnancy, the aim of this study was to compare echogenic fluid on
      sonography with the results of culdocentesis in predicting hemoperitoneum.
      MATERIALS AND METHODS: Free fluid on transvaginal sonography and the results of
      culdocentesis were correlated with the presence or absence of hemoperitoneum in
      46 patients at surgery. Forty ectopic pregnancies and six nonectopic pregnancies
      were found. Echogenic fluid was the criterion used to establish hemoperitoneum on
      sonography. For statistical analysis, negative and nondiagnostic culdocentesis
      results were combined. The sensitivity, specificity, and positive and negative
      predictive values of each diagnostic technique were compared. RESULTS: In 40 of
      46 patients with ectopic pregnancy, the sensitivity and specificity of echogenic
      fluid for establishing hemoperitoneum were 100% and 100%, respectively, compared
      with 66% and 80%, respectively, for culdocentesis. More important, the negative
      predictive value of a nondiagnostic culdocentesis was 25% compared with 100% for
      echogenic fluid in the ectopic subgroup of patients. In two patients with
      incomplete abortions, sonography failed to detect small amounts of hemoperitoneum
      at surgery performed 4 hr and 7 days after sonography. CONCLUSION: Sonography is
      more sensitive than culdocentesis in the detection of hemoperitoneum.
      Culdocentesis is invasive, and nondiagnostic results cannot be used to exclude
      hemoperitoneum. Culdocentesis should play no role in the evaluation of ectopic
      pregnancy except in the unusual circumstance in which high-resolution sonography
      cannot be readily performed.

PMID- 9574607
TI  - Virtual colonoscopy: imaging features with colonoscopic correlation.

PMID- 9574608
TI  - Small-bowel obstruction associated with sigmoid diverticulitis: CT evaluation in
      16 patients.
AB  - OBJECTIVE: The purpose of this study was to identify acute sigmoid diverticulitis
      as a cause of small-bowel obstruction and to describe the CT findings.
      CONCLUSION: CT scanning enabled accurate preoperative diagnosis of colonic
      diverticulitis as the cause of the small-bowel obstruction, thereby allowing
      proper management and surgical planning.

PMID- 9574609
TI  - Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography.
AB  - OBJECTIVE: The purpose of this study was to compare dual-phase helical CT and
      endosonography for the diagnosis and staging of pancreatic tumors. SUBJECTS AND
      METHODS: Thirty patients with suspected pancreatic tumors underwent
      endosonography and dual-phase helical CT. A pathologic diagnosis was obtained in
      all cases with surgery (n = 23) or biopsy (n = 7), resulting in 27 neoplasms.
      Dual-phase helical CT and endosonographic findings were correlated with surgical
      and pathologic findings to determine diagnosis and resectability of pancreatic
      tumors. RESULTS: Overall diagnostic sensitivity was 92% for dual-phase helical CT
      and 100% for endosonography (p = .45). Overall accuracy for staging of pancreatic
      tumors was 93% for both dual-phase helical CT and endosonography. Overall
      accuracy for predicting resectability was 90% for both dual-phase helical CT and
      endosonography. Accuracy of predicting unresectability was 100% for dual-phase
      helical CT and 86% for endosonography (p > .80). Differences were not considered
      statistically significant. CONCLUSION: Dual-phase helical CT and endoscopic
      sonography do not differ significantly for diagnosis and assessment of
      resectability of pancreatic tumors.

PMID- 9574610
TI  - Autoimmune pancreatitis: CT and MR characteristics.
AB  - OBJECTIVE: Our goal was to elucidate the CT and MR imaging characteristics in
      patients with autoimmune pancreatitis, which is a reversible chronic pancreatitis
      with an autoimmune cause. CONCLUSION: On CT and MR imaging, a capsulelike rim,
      which is thought to correspond to an inflammatory process involving
      peripancreatic tissues, appears to be a characteristic finding of autoimmune
      pancreatitis. Also, diffuse pancreatic enlargement along with hypointensity on T1
      weighted MR images and delayed enhancement on dynamic CT and MR studies are other
      features of this disorder.

PMID- 9574612
TI  - Clinical and pathologic variants of appendiceal disease: CT features.

PMID- 9574611
TI  - Meckel's diverticulum: angiographic findings in 16 patients.
AB  - OBJECTIVE: The purpose of this study was to assess the sensitivity of angiography
      in revealing the vitellointestinal artery or other arteriographic abnormalities
      in patients in whom surgery subsequently proved Meckel's diverticulum. MATERIALS
      AND METHODS: From the 36 patients who had undergone a Meckel's diverticulectomy
      between 1980 and 1997 at Hammersmith Hospital or a referring hospital, we
      selected 18 who had undergone preoperative angiography at our institution. Case
      notes and angiograms of these 18 patients were reviewed for the presence of a
      persistent vitellointestinal artery or other angiographic evidence of a Meckel's
      diverticulum. RESULTS: Angiograms of 16 of 18 patients were available for review.
      A striking male preponderance existed (male:female = 13:3). Mean age was 28 years
      (range, 12-65 years). In 11 (69%) of the 16 patients, a persistent
      vitellointestinal artery was seen that had been noted at the time of the study
      and reported before surgery for nine patients. Other angiographic abnormalities
      at the site of the Meckel's diverticulum were present in four patients and
      included a vascular blush, early venous return, and arterial irregularity.
      CONCLUSION: Angiography will show a persistent vitellointestinal artery in most
      individuals with a Meckel's diverticulum who present with chronic
      gastrointestinal bleeding. However, the recognition of a persistent
      vitellointestinal artery may be difficult because of overlying vessels, and
      superselective catheterization of distal ileal arteries may be necessary.

PMID- 9574613
TI  - Helical CT versus CT arterial portography in the detection of hepatic metastasis
      of colorectal carcinoma.
AB  - OBJECTIVE: The study is a prospective comparison of helical CT with nonhelical CT
      arterial portography (CTAP) in the detection of liver metastases from colorectal
      carcinoma, using surgical and histologic findings as the gold standard. SUBJECTS
      AND METHODS: Thirty-five patients with colorectal carcinoma and suspected liver
      metastases were prospectively examined with helical CT and CTAP before surgery.
      In nine cases, surgery was not performed. In the remaining 26 patients, imaging
      results were correlated with surgical and pathologic findings. Three radiologists
      prospectively assessed metastatic involvement with both techniques. The results
      were compared with pathologic and surgical findings on a lesion-by-lesion basis.
      In a second phase, three radiologists not directly concerned in the design of the
      study independently assessed metastatic involvement of the liver as revealed on
      helical CT and CTAP on a segment-by-segment basis with a five-level scale of
      confidence. Results were analyzed by receiver operating characteristic methods.
      RESULTS: The results of the histologic study disclosed 50 metastatic lesions.
      Helical CT had a sensitivity of 76% (38/50) and a positive predictive value of
      90%. CTAP had a sensitivity of 74% (37/50) and positive predictive value of 69%.
      Receiver operating characteristic analysis revealed a greater area under the
      curve (Az index), 0.96, for helical CT than for CTAP (0.86). Differences were
      statistically significant (p < .001). CONCLUSION: Helical CT is superior to
      nonhelical CTAP in the detection of hepatic metastases from colorectal carcinoma.

PMID- 9574614
TI  - Air trapping on expiratory high-resolution CT scans in the absence of inspiratory
      scan abnormalities: correlation with pulmonary function tests and differential
      diagnosis.
AB  - OBJECTIVE: We wish to describe the differential diagnosis and pulmonary function
      correlates of patients with normal findings on inspiratory high-resolution CT
      (HRCT) scans who showed air trapping on expiratory scans. MATERIALS AND METHODS:
      HRCT scans in 273 consecutive patients with suspected diffuse lung disease were
      reviewed. HRCT consisted of inspiratory scans at 1- to 2-cm intervals and
      expiratory scans at three levels. Studies considered to show expiratory air
      trapping were divided into two groups, one having normal findings on inspiratory
      scans and one having abnormal findings on inspiratory scans. Pulmonary function
      test results in these groups were compared with a group of patients who had
      normal findings on inspiratory and expiratory HRCT scans. RESULTS: Forty-five
      patients showed air trapping on expiratory HRCT scans. Of these 45 patients,
      inspiratory high-resolution CT scans showed abnormal findings in 36
      (bronchiectasis, bronchiolitis obliterans, asthma, chronic bronchitis, and cystic
      fibrosis). In the remaining nine patients, inspiratory HRCT had normal findings;
      conditions in these nine patients included bronchiolitis obliterans (n = 5),
      asthma (n = 3), and chronic bronchitis (n = 1). Results of pulmonary function
      tests in patients with air trapping and normal findings on inspiratory scans were
      intermediate, falling between those of patients with normal findings on
      inspiratory and expiratory HRCT scans and those of patients with air trapping and
      abnormal findings on inspiratory scans. CONCLUSION: Air trapping on expiratory
      HRCT scans in patients with normal findings on inspiratory scans is most often
      associated with bronchiolitis obliterans and asthma. Obtaining expiratory scans
      in patients who may have one of these diseases is recommended.

PMID- 9574615
TI  - Three-dimensional volumetric assessment of abnormally low attenuation of the lung
      from routine helical CT: inspiratory and expiratory quantification.
AB  - OBJECTIVE: The purpose of this investigation was to quantitatively assess
      abnormally low attenuation of the lung by use of three-dimensional volumetric
      reconstructions from routine helical CT and to assess their correlation with
      pulmonary function tests. MATERIALS AND METHODS: Helical CT was performed in 100
      patients in full inspiration. Examination was also performed in full expiration
      in 53 of these patients. Three-dimensional volumetric reconstructions were
      performed for total lung volumes at inspiration and at expiration, with a
      threshold of -896 H on inspiratory CT and -790 H on expiratory CT, to quantify
      emphysematous change. Correlation was made with pulmonary function tests in 79
      patients. RESULTS: CT volumetric assessments of abnormally low attenuation of the
      lung at inspiration and expiration had a high correlation (r2 = .84, p < or =
      .0001). In comparison with pulmonary function tests, both inspiratory low
      attenuation of the lung and expiratory low attenuation of the lung correlated
      well with the logarithm of the ratio of the forced expiratory volume in 1 sec
      (FEV1) to the forced vital capacity (r2 = .74, p < or = .0001 and r2 = .74, p <
      or = .0001, respectively) and with the percentage of predicted ratio of the FEV1
      to the forced vital capacity (r2 = .69, p < or = .0001 and r2 = .69, p < or =
      .0001, respectively). Linear correlations were also seen with FEV1, residual
      volume, and forced residual capacity. CONCLUSION: Three-dimensional volumetric
      reconstructions of hypoattenuating lung correlate well with pulmonary function
      tests. In addition, inspiratory and expiratory data are also correlative,
      suggesting that a dedicated expiratory examination is not needed. This easily
      obtainable information will prove useful for patients with obstructive lung
      disease from emphysema, providing a measure of pulmonary function status in this
      population.

PMID- 9574616
TI  - Virtual bronchoscopy for directing transbronchial needle aspiration of hilar and
      mediastinal lymph nodes: a pilot study.
AB  - OBJECTIVE: We conducted a preliminary investigation of virtual bronchoscopy as a
      guide for transbronchial needle aspiration of hilar or mediastinal lymph nodes to
      assess the usefulness of this technique. CONCLUSION: Virtual bronchoscopic images
      derived from routine helical CT scans were useful for directing transbronchial
      needle aspiration in a clinical setting. In addition, virtual bronchoscopy may
      have been responsible for improving the yield of transbronchial needle
      aspirations done by our bronchoscopists when 22-gauge needles were used.

PMID- 9574617
TI  - Anomalies of pulmonary veins: usefulness of spin-echo and gradient-echo MR
      images.
AB  - OBJECTIVE: We compared the value of spin-echo and gradient-echo MR images in the
      evaluation of anomalies of pulmonary veins. MATERIALS AND METHODS: Fourteen
      patients with a variety of developmental anomalies of pulmonary veins underwent
      MR imaging examination. Axial T1-weighted spin-echo and gradient-echo MR images
      were evaluated retrospectively on separate occasions during which visualization
      of normal and anomalous pulmonary veins was determined. RESULTS: Of 52 pulmonary
      veins, 46 (88%) were identified on T1-weighted spin-echo images and 50 (96%) on
      gradient-echo images. Two patients had atresia of both left pulmonary veins. Of
      14 anomalous veins, 11 (79%) were revealed on spin-echo images and 13 (93%) on
      gradient-echo images. CONCLUSION: Both spin-echo and gradient-echo MR images were
      accurate in revealing anomalies of pulmonary veins. In our study, gradient-echo
      images were equal or superior to spin-echo images.

PMID- 9574619
TI  - Apocrine metaplasia: mammographic and sonographic appearances.
AB  - OBJECTIVE: Our objective was to evaluate the mammographic and sonographic
      appearances of apocrine metaplasia and correlate imaging and histopathologic
      findings. MATERIALS AND METHODS: Retrospective review of 408 lesions in 318
      consecutive patients undergoing core needle biopsy (n = 370) or fine needle
      aspiration (n = 38) revealed 46 cases of apocrine metaplasia. In 17 of these
      cases, apocrine metaplasia represented more than 50% of the lesion sampled; these
      17 lesions formed the basis for analysis. RESULTS: On mammography, all 17 cases
      appeared as new or enlarging equal-density (n = 15) or low-density (n = 2) masses
      with an average size of 12.8 mm. Borders were microlobulated in 59% (10/17),
      macrolobulated in 29% (5/17), and circumscribed or oval in 12% (2/17). Sonography
      revealed a lobulated mass containing a cluster of small (2- to 5-mm) anechoic
      foci and intervening septae in 77% (10/13) of cases. A discrete hypoechoic solid
      component was seen in 23% of cases (3/13). Posterior acoustic enhancement was
      seen in 85% of cases (11/13). In 65% of lesions (11/17), we noted a decrease in
      size or total resolution during biopsy or fine needle aspiration. Histopathologic
      examination showed the typical appearance of dilated cystic acini lined by
      apocrine metaplastic epithelium. CONCLUSION: On mammography, the combined
      findings of an equal- or low-density microlobulated or lobulated mass that
      corresponds on sonography to a cluster of small (2- to 5-mm) anechoic foci with
      intervening septae should suggest the diagnosis of focal apocrine metaplasia.
      With radiologists' increasing experience, follow-up, rather than biopsy, of such
      typical-appearing lesions may be adequate.

PMID- 9574618
TI  - Evaluation of primary pulmonary carcinoid tumors using FDG PET.
AB  - OBJECTIVE: The purpose of this study was to determine the spectrum of positron
      emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) findings in patients
      who have primary pulmonary carcinoid tumors. CONCLUSION: On FDG PET imaging,
      pulmonary carcinoid tumors usually have lower FDG uptake than expected for
      malignant tumors. Biopsy or close radiologic follow-up is therefore recommended
      for solitary pulmonary nodules that are clinically suspected of being carcinoid
      tumors and that do not show increased metabolic activity on FDG PET images.

PMID- 9574620
TI  - Effect of patient position on sonographically measured renal length in neonates,
      infants, and children.
AB  - OBJECTIVE: Renal length as measured on sonography is fundamental in the
      evaluation of renal disease in children. Understanding the effect of patient
      position and imaging plane on measured renal length is important for the
      appropriate use of the standards for interpretation. The goal of this study was
      to determine how measurement of renal length on sonograms is affected by changes
      in patient position and imaging plane. SUBJECTS AND METHODS: One hundred seventy
      six neonates, infants, and children who were 2 days to 17 years old underwent
      sonography froin October 1995 through June 1996. The largest long-axis renal
      dimension in sagittal, coronal, and prone planes was obtained for each kidney.
      Data were analyzed separately for each kidney to determine the individual
      variation of renal length. RESULTS: The correlation between maximum renal length
      on coronal, sagittal, and prone sonograms was greater than .95 for both right and
      left kidneys. The coronal plane yielded the largest measured renal length and the
      prone view, the smallest. The median of the absolute value of the differences
      between individual renal lengths as measured on sonograms in the different
      imaging planes was 2-3 mm for both left and right kidneys (mean difference, left
      kidney = 3.34-3.62 mm; mean difference, right kidney = 3.22-3.68 mm). CONCLUSION:
      The coronal and sagittal views yield the longest measurements and prone views,
      the shortest. Therefore, initial measurements should be made in coronal or
      sagittal planes. Prone views should be reserved for situations in which the
      suspicion exists that the kidney was foreshortened on other views. Reference
      standards done in a particular plane should be applicable in most situations
      regardless of the patient position necessary to obtain optimum length.

PMID- 9574621
TI  - Intraperitoneal rhabdomyosarcoma in children: incidence and imaging
      characteristics on CT.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and CT
      imaging features of intraperitoneal rhabdomyosarcoma in children. CONCLUSION:
      Approximately 10% of children with rhabdomyosarcoma may have intraperitoneal
      neoplastic involvement either at the time of diagnosis or subsequently. On CT,
      intraperitoneal rhabdomyosarcomas are associated with ascites, enhancing nodules,
      masses, a pseudomyxoma peritonei-like appearance, and omental caking.

PMID- 9574622
TI  - Neoplastic fixation to the prevertebral compartment by squamous cell carcinoma of
      the head and neck.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy of MR imaging
      in determining fixation of squamous cell carcinomas to the prevertebral space.
      MATERIALS AND METHODS: MR images of 15 patients with large pharyngeal carcinoma
      (n = 13) or laryngeal carcinomas with pharyngeal extension (n = 2) were
      retrospectively reviewed independently by two head and neck radiologists who were
      unaware of the surgical findings. MR images were evaluated for four criteria in
      the prevertebral longus muscle complex: muscle concavity, irregular tumor-muscle
      interface, T2 hyperintensity, and enhancement. All patients underwent
      panendoscopy where fixation or mobility of the tumor relative to the prevertebral
      fascia was assessed by manual manipulation. Tumors in six patients were fixed to
      the prevertebral space and inoperable. In nine patients whose tumors were not
      fixed, open neck explorations were performed and tumors were resected in seven
      patients. MR findings were compared with panendoscopy in all patients and with
      intraoperative assessment in nine patients. RESULTS: Eleven of 15 patients had at
      least two of the MR imaging criteria present. None of the MR findings were both
      sensitive and specific for tumor fixation. Although muscle concavity and
      enhancement each had a sensitivity of 88%, both criteria suffered from low
      specificity (14% and 29%, respectively). An irregular tumor-muscle interface and
      muscle T2 hyperintensity were criteria that suffered from both low sensitivity
      and specificity. Accuracy of the imaging criteria independently ranged from 53%
      to 60%. CONCLUSION: Although abnormal muscle contour, T2 hyperintensity, and
      enhancement are frequently present in neck carcinomas that are fixed to the
      prevertebral space, these findings may also be present in patients in whom the
      tumor is mobile and resectable. MR imaging may not be able to differentiate
      between neoplastic fixation and nonneoplastic changes in the prevertebral space.

PMID- 9574623
TI  - Equal rights for all--except for doctors.

PMID- 9574624
TI  - Imaging of pelvic postpartum complications.

PMID- 9574625
TI  - Imaging of puerperal septic thrombophlebitis: primary role for sonography.

PMID- 9574626
TI  - Fibroglandular breast tissue assessments by mammography and MR imaging.

PMID- 9574627
TI  - Environmentally conscious film masking system for mammography.

PMID- 9574628
TI  - CT of spontaneous hemothorax from intrapleural rupture of a pulmonary
      arteriovenous malformation.

PMID- 9574629
TI  - Bloody nipple discharge after lumpectomy.

PMID- 9574630
TI  - MR imaging of traumatic closed injuries of the biceps brachii muscle in military
      parachutists.

PMID- 9574631
TI  - Multiple endocrine neoplasia syndrome, type 2B.

PMID- 9574632
TI  - Science in neurosurgery: the importance of the scientific method.
AB  - The scientific method offers a way for a neurosurgeon to assess objectively his
      or her professional activities, especially in regard to the results of treatment.
      For this reason, all neurosurgical trainees should be instructed in at least the
      basic tenets of the scientific method, and all neurosurgeons should be guided by
      these tenets in their daily practice.

PMID- 9574633
TI  - Biology of neurological recovery and functional restoration after spinal cord
      injury.
AB  - OBJECTIVE: This article reviews the anatomic and pathophysiological bases for
      recovery of neurological function after experimental or clinical spinal cord
      injury (SCI). METHODS: Current knowledge regarding the recovery of neurological
      function after experimental or clinical SCI was reviewed to determine the
      biological basis of neurological recovery. RESULTS: There is a great propensity
      for recovery after clinical or experimental SCI. An examination of the anatomic
      basis of recovery indicates that there is a potential for both root and cord
      recovery, with the latter involving recovery of both gray and white matter of the
      cord. Resolution of acute injury events, such as hemorrhaging, and resolution of
      secondary pathophysiological processes, such as ischemia and excitotoxicity, can
      each account for recovery. The third recovery mechanism involves regrowth or
      regeneration of nervous tissue, resulting from either inherent or induced
      processes. CONCLUSION: During the Decade of the Brain, there has been a profusion
      of very promising in vitro and in vivo studies that have shown enhanced
      neurological recovery after experimental or clinical SCI.

PMID- 9574635
TI  - Accumulation of p53 and Ki-67 expression do not predict survival in patients with
      fibrillary astrocytomas or the response of these tumors to radiotherapy.
AB  - OBJECTIVE: Although radiotherapy is often used in the treatment of patients with
      low-grade astrocytomas, its value is still uncertain. Radiotherapy carries a risk
      of morbidity for patients and has time and cost implications for health services.
      We have assessed the value of two histological variables, p53 accumulation and Ki
      67 expression, in predicting the response of astrocytomas to radiotherapy. The
      former antigen was assessed because many astrocytic tumors show mutations in the
      p53 gene, the function of which is crucial for mediating cell death after
      radiotherapy, and the latter was assessed because it is expressed only in
      proliferating tumor cells, which may show greater radiosensitivity than
      nonproliferating cells. METHODS: Immunohistochemistry was used to detect the
      accumulation of p53 and expression of Ki-67 in a retrospective series of 96
      patients with supratentorial fibrillary astrocytomas, 58 of whom had received
      postoperative radiotherapy. The immunohistochemical data were correlated with
      survival after radiotherapy. RESULTS: There was no significant difference in
      survival between the patients who did and those who did not receive radiotherapy.
      The p53 and Ki-67 labeling indices did not correlate with survival in either the
      irradiated or the nonirradiated cohort, nor with overall survival in the series
      as a whole. CONCLUSION: Immunohistochemical assessment of p53 accumulation and Ki
      67 expression does not help in predicting the survival of patients with
      supratentorial fibrillary astrocytomas or in predicting whether particular
      patients are likely to benefit from radiotherapy.

PMID- 9574636
TI  - Tumor-related venous obstruction and development of peritumoral brain edema in
      meningiomas.
AB  - OBJECTIVE: The exact pathogenesis of peritumoral brain edema (PTBE) in
      meningiomas is still unknown. A number of different pathophysiological hypotheses
      have been considered. A detrimental effect of tumor-related venous obstruction
      has been suggested as one pathogenetic mechanism. We sought to characterize the
      significance of venous stasis in the development of PTBE in meningiomas. METHODS:
      Angiograms for 134 patients with 136 intracranial meningiomas were analyzed.
      Pathological changes affecting cortical veins, sylvian veins, bridging veins,
      deep veins, transmedullary veins, and dural sinuses were evaluated. From
      preoperative computed tomographic scans, the total tumor volume, the tumor/PTBE
      volume ratio (edema index [EI]), and the location of the edema were determined.
      For statistical evaluation, meningiomas associated with pathological venous
      drainage were compared with size-matched controls. RESULTS: The edema incidence
      and the mean EI were not different for meningiomas with unselected signs of
      obstructed venous drainage, compared with controls. In particular, lesions with
      involvement of cortical veins, bridging veins, and dural sinuses showed no higher
      edema incidence. However, meningiomas associated with venous changes in sylvian
      veins (EI = 4.9 versus EI = 2.7; P < 0.004) and with dysplastic transmedullary
      veins (EI = 3.3 versus EI = 1.7; P < 0.04) showed significantly higher mean EI
      values, compared with meningiomas without involvement of these vessels.
      CONCLUSION: Our data suggest that tumor-related venous obstruction does not play
      an essential role in the development of PTBE for the majority of meningiomas. For
      a small subgroup of meningiomas with involvement of sylvian veins or development
      of dysplastic transmedullary veins, changes in venous drainage may aggravate
      preexisting PTBE.

PMID- 9574634
TI  - Survival and functional status after resection of recurrent glioblastoma
      multiforme.
AB  - OBJECTIVE: To determine the selection factors for and results of second
      resections performed to treat recurrent glioblastoma multiforme (GM), we studied
      301 patients with GM who were treated from the time of diagnosis using two
      prospective clinical protocols. METHODS: The patients were prospectively followed
      from the time of diagnosis, using clinical and radiographic criteria after
      maximal surgical resection and external beam radiotherapy with or without
      adjuvant chemotherapy. Resection of recurrent GM was performed at the
      recommendation of the treating clinicians. The results of the second resections
      were retrospectively reviewed and analyzed using multivariate logistic
      regression, Kaplan-Meier-Turnbull survival analysis, Cox regression, and
      propensity score stratification. RESULTS: Forty-six patients underwent second
      resections during the study period. The actuarial rate of the second resections
      was 15% of the patients 1 year after diagnosis and 31% 2 years after diagnosis.
      Younger age (P = 0.01) and more extensive initial resection (P = 0.02), but not
      Karnofsky Performance Scale (KPS) score at the time of diagnosis or recurrence,
      predicted a higher chance of selection for reoperation after initial tumor
      recurrence. Twenty-eight percent of the patients had improved KPS scores after
      undergoing reoperation, 49% were stable, and 23% had declines in KPS scores of 10
      to 30 points. There was no operative mortality. After reoperation, 85% of the
      patients received chemotherapy, 11% received brachytherapy or underwent
      stereotactic radiosurgery, and 17% underwent third resections. The median
      survival period after reoperation was 36 weeks. Higher preoperative KPS scores
      predicted longer survival periods after reoperation (P = 0.03). Age and interval
      since diagnosis were not significant prognostic factors. The median high-quality
      survival period (KPS score, > or =70) was 18 weeks. The median survival period
      after first tumor progression was 23 weeks for 130 patients treated using the
      same protocols who did not undergo reoperations. Patients who did undergo
      reoperations experienced clinically and statistically significantly longer
      survival periods. However, this was determined to be partially because of
      selection bias. CONCLUSION: Survival after resection of recurrent GM remains poor
      despite advances in imaging, operative technique, and adjuvant therapies. High
      quality survival after resection of recurrence to treat GM seems to have
      increased significantly since an earlier report from our institution.

PMID- 9574637
TI  - Pathological changes in surgically resected angiographically occult vascular
      malformations after radiation.
AB  - OBJECTIVE: The goal of this study was to evaluate the pathological changes
      associated with radiation treatment (stereotactic radiosurgery or conventional
      irradiation) of angiographically occult vascular malformations (AOVMs). METHODS:
      Eleven patients underwent surgical resection of an AOVM in the mesial temporal
      lobe, brain stem, thalamus, or basal ganglia after previous radiation treatment.
      The indications for surgery were recurrent symptomatic bleeding from the lesion
      in 10 patients and recurrent intractable seizures in 1 patient. Radiation was
      used as the initial therapy because the risk of surgical resection was deemed too
      high. Three patients received conventional radiation therapy of 3000 to 5400 rads
      at an outside institution. One patient received radiosurgery with the gamma knife
      at another institution using a dose of 15 Gy to the margin. The remaining 7
      patients received stereotactic radiosurgery with a helium-ion particle beam. The
      dose range was from 18 to 26 Gy equivalents. The interval from radiation to
      surgical resection ranged from 1 to 10 years, with a mean of 3.5 years. These
      lesions were compared with 10 nonirradiated cavernous malformations. RESULTS: One
      irradiated lesion was identified pathologically as a true arteriovenous
      malformation despite being angiographically occult. This lesion did not
      demonstrate significant changes in the vasculature but did have radiation
      necrosis of the surrounding brain 5 years after 25 Gy equivalents of helium-ion
      radiosurgery. Two other specimens were too small to identify the type of vascular
      malformation adequately. Of the remaining eight malformations identified as
      cavernous malformations, six showed a combination of marked fibrosis of the
      vascular channels, fibrinoid necrosis, and ferrugination. However, the fibrinoid
      necrosis was the only finding unique to the irradiated lesions compared with
      nonirradiated controls. All the irradiated lesions still had patent vascular
      channels; none were completely thrombosed. CONCLUSION: Radiosurgery or
      conventional radiation therapy did not cause histologic vascular obliteration in
      intracranial AOVMs evaluated 1 to 10 years (mean 3.5 yr) after radiation
      delivery. It should be recognized that these patients are irradiation failures
      who may not be representative of all irradiated patients. However, recurrent
      bleeding from AOVMs may relate to poor radiation response in some patients.

PMID- 9574638
TI  - Clinically nonsecreting pituitary adenomas in childhood and adolescence.
AB  - OBJECTIVE AND PATIENTS: Clinically nonsecreting pituitary adenomas are rare in
      childhood and adolescence. We analyzed five cases of clinically nonsecreting
      pituitary adenomas in patients (4 male and 1 female patient) under 20 years of
      age at surgery (0.22%), identified by a review of 2288 patients with pituitary
      adenomas treated from 1970 to 1996 at the Hamburg University. CLINICAL
      PRESENTATION AND RESULTS: Patient age at the onset of symptoms ranged from 8 to
      13 years (mean, 10.8 yr), and age at surgery ranged from 12.5 to 19.5 years
      (mean, 15.5 yr). Two patients presented with endocrine symptoms, two with
      headache only, and one with a visual field defect. Endocrinological examinations
      showed pituitary insufficiency in two patients with endocrine symptoms. The serum
      prolactin level was normal in all patients. Radiological investigations
      demonstrated resectable macroadenomas with ring enhancement in four patients and
      a nonresectable macroadenoma with parasellar extension in one. Transnasal
      explorations achieved radical tumor resection except in one patient. The latter
      underwent a transcranial resection and radiotherapy because of parasellar tumor
      rest. Surgical morbidity consisted of left oculomotor nerve palsy after
      transcranial exploration. In two patients, normal pituitary function was
      preserved by transnasal surgery. Follow-up duration was 2 to 23 years (mean, 10.9
      yr). There was no recurrence except for one parasellar adenoma.
      Immunohistological diagnosis was null cell adenoma in two patients, silent
      prolactinoma in two, and silent gonadotroph adenoma in one. The proliferative
      activity measured by Ki-67 (as the antibody MIB-1) and p53 expression revealed a
      positive reaction in one adenoma with parasellar extension. CONCLUSION:
      Clinically nonsecreting pituitary adenomas in childhood and adolescence cause
      different endocrine symptoms from those in adults. They caused pubertal and
      growth delay and/or primary amenorrhea in the patients investigated in this
      study. Transnasal surgery in childhood and adolescence is as safe as in adults.
      The characteristics of nonsecreting pituitary adenomas in this age group,
      including 20 patients cited from the literature, do not differ from those in
      adults.

PMID- 9574639
TI  - Cerebral blood flow measurement as an indicator for an indirect revascularization
      procedure for adult patients with moyamoya disease.
AB  - OBJECTIVE: Some adult patients with moyamoya disease have been treated
      successfully by indirect revascularization alone, although surgical indications
      and hemodynamic changes for these patients have not been fully explored. To
      examine surgical indications for this procedure, we studied the regional cerebral
      blood flow (rCBF) and angiographic findings in adult patients with moyamoya
      disease preoperatively and postoperatively. METHODS: On 17 hemispheric sides of
      12 adult patients with moyamoya disease treated surgically with a combination of
      various indirect procedures, mainly by encephaloduroarteriosynangiosis, we
      retrospectively evaluated changes in rCBF using xenon-133 single photon emission
      computed tomography, angiographic collateral formation, and clinical results.
      RESULTS: Preoperatively, the rCBF values in the cortices at the bypass site at
      rest and after acetazolamide loading were lower than normal. The rCBF values were
      significantly increased after revascularization, approaching normal, except for
      incomplete recovery of vascular reactivity. The extent of postoperative
      neovascularization from implanted tissues fed by the external carotid artery
      system was more developed, in parallel with the preoperative decrease in resting
      and loading rCBF values. One-third of the operated sides exhibiting both a low
      rCBF at rest and impaired vascular reactivity in the noninfarcted cortices
      achieved good revascularization over two-thirds of the middle cerebral artery
      territory, accompanied by rCBF improvement and moyamoya vessel regression. Enough
      potential for neovascularization in the noninfarcted cortices was indicated that
      the resting rCBF was lower than 50 ml/100 g per minute (below the normal value by
      2 standard deviations) and did not increase more than that value after loading,
      even in a 40-year-old patient who presented with a hemorrhage. Clinically, 11
      patients (92%) had good results at the 4-year follow-up, whereas 1 patient (8%)
      with unsatisfactory neovascularization and a lesser extent of moyamoya vessel
      reduction experienced rebleeding. CONCLUSION: We conclude that for the surgical
      treatment of adult patients with moyamoya disease, indirect procedures, mainly
      encephaloduroarteriosynangiosis, are recommended for patients with lower rCBF and
      no or negative vascular reactivity in the noninfarcted cortices, as well as for
      those who have no indication for the direct procedure. It is possible to
      determine these indications by a xenon-133 inhalation single photon emission
      computed tomographic study including an acetazolamide challenge test.

PMID- 9574640
TI  - Effect of 5% albumin solution on sodium balance and blood volume after
      subarachnoid hemorrhage.
AB  - OBJECTIVE: Subarachnoid hemorrhage (SAH) predisposes patients to excessive
      natriuresis and volume contraction. We studied the effects of postoperative
      administration of 5% albumin solution on sodium balance and blood volume after
      SAH. We also sought to identify physiological variables that influence renal
      sodium excretion after SAH. METHODS: Forty-three patients with acute SAH were
      randomly assigned to receive hypervolemia or normovolemia treatment for a period
      of 7 days after aneurysm clipping. In addition to a base line infusion of normal
      saline solution (80 ml/hr), 250 ml of 5% albumin solution was administered every
      2 hours for central venous pressure (CVP) values of < or =8 mm Hg (hypervolemia
      group, n = 19) or < or =5 mm Hg (normovolemia group, n = 24). RESULTS: Both
      groups demonstrated relative volume expansion in base line measurements. The
      hypervolemia group received significantly more total fluid, sodium, and 5%
      albumin solution than did the normovolemia group and had higher CVP values and
      serum albumin levels (all P < 0.02). Cumulative sodium balance was even in the
      hypervolemia group and persistently negative in the normovolemia group, because
      of sodium losses that occurred on Postoperative Days 2 and 3 (P = 0.03). In a
      multiple-regression analysis of all patients, 24-hour sodium balance correlated
      negatively with glomerular filtration rate (GFR) and positively with serum
      albumin levels, after correction for sodium intake (P < 0.0001). Hypervolemia
      therapy seemed to paradoxically lower GFR (P = 0.10) and had no effect on blood
      volume, which declined by 10% in both groups. Pulmonary edema requiring diuresis
      occurred in only one patient in the hypervolemia group. CONCLUSION: Supplemental
      5% albumin solution given to maintain CVP values of >8 mm Hg prevented sodium and
      fluid losses but did not have an impact on blood volume in our patients, who were
      hypervolemic in base line measurements. The natriuresis that occurs after SAH may
      be mediated in part by elevations of GFR. In addition to acting as a colloid
      volume expander, 5% albumin solution lowers the GFR and promotes renal sodium
      retention after SAH. These properties may limit the amount of total fluid
      required to maintain a given CVP value and hence may minimize the frequency of
      pulmonary edema.

PMID- 9574641
TI  - The dilemma of discontinuation of anticoagulation therapy for patients with
      intracranial hemorrhage and mechanical heart valves.
AB  - BACKGROUND: Anticoagulant-related hemorrhage occurs with an incidence of
      approximately 1%/patient-year in mechanical heart valve recipients. Intracranial
      hemorrhage poses a difficult clinical choice; continuing anticoagulation therapy
      may enlarge the volume of the hemorrhage, early reinstitution of anticoagulation
      therapy may predispose patients to recurrence, and reversal of anticoagulation
      therapy may place patients at risk for systemic embolization involving the brain.
      The risk of embolization may also be greater for patients with atrial
      fibrillation, cage-ball valves in the mitral position, and reduced ventricular
      function. This dilemma exists because of a lack of data for a large series of
      patients. METHODS: We reviewed the medical records and neuroimaging studies for a
      consecutive group of patients admitted with intracranial hemorrhage and
      mechanical heart valves. We reviewed neurological presenting data, cardiac risk
      factors for systemic embolization (atrial fibrillation, enlarged atrial chambers,
      reduced ventricular function, and the type and location of the metallic valve),
      and hospital management. RESULTS: We studied 39 patients with intracranial
      hemorrhage and mechanical heart valves (median age, 69 yr). Four patients had
      experienced previous transient ischemic attacks or minor strokes. The time from
      valve replacement to intracranial hemorrhage ranged from 2 months to 19 years
      (median, 6 yr). The type of intracranial hemorrhage was acute subdural hematoma
      (n = 20), lobar hematoma (n = 10), subarachnoid hemorrhage (n = 4), cerebellar
      hematoma (n = 3), or basal ganglionic hematoma (n = 2). Thirteen patients died
      within 2 days of admission. All 26 surviving patients received fresh frozen
      plasma and vitamin K. Fifteen patients underwent evacuation of acute subdural
      hematoma, and in one patient an anterior communicating aneurysm was clipped. The
      duration of discontinuation of anticoagulation therapy varied from 2 days to 3
      months (median, 8 d). None of the patients developed transient ischemic attacks,
      ischemic strokes, valve thrombosis, or systemic embolization. No recurrence of
      intracranial hemorrhaging was observed during hospitalization and reinstitution
      of anticoagulation or antiplatelet agent administration. CONCLUSION: Temporary
      interruption of anticoagulation therapy seems safe for patients with intracranial
      hemorrhage and mechanical heart valves but without previous evidence of systemic
      embolization. For most patients, discontinuation for 1 to 2 weeks should be
      sufficient to observe the evolution of a parenchymal hematoma, to clip or coil a
      ruptured aneurysm, or to evacuate an acute subdural hematoma.

PMID- 9574642
TI  - The posterior approach to a series of glomus (Type II) intramedullary spinal cord
      arteriovenous malformations.
AB  - OBJECTIVE: Intramedullary spinal cord arteriovenous malformations (AVMs) are
      comprised of those AVMs which in either glomus or nidal form are found partially
      or entirely within the substance of the spinal cord. An effort to subdivide these
      lesions into either glomus Type II or juvenile Type III spinal cord AVMs has
      underscored the diffuse, unresectable nature of the latter but has done little to
      suggest a logical management paradigm for the more well-defined, low-flow glomus
      lesion. METHODS: To address this shortcoming, 15 cases of glomus Type II spinal
      AVMs were identified from a larger series of a variety of spinal AVMs. Computed
      tomography, magnetic resonance imaging, and superselective angiography rendered
      the anatomic diagnosis of these lesions accurate in all cases. All lesions were
      approached posteriorly via a standard laminectomy, with the goal of total
      extirpation, and all patients underwent immediate postoperative angiography to
      verify cure. In the vast majority of cases, patients underwent follow-up imaging
      to confirm the durability of this cure, and long-term outcome was determined
      using both a subjective quality of life assay and a functional grading scale.
      Age, sex, mode of presentation, and radiographic features were subsequently
      analyzed with respect to functional outcome. RESULTS: Most glomus spinal AVMs
      presented with a rapid cascade of signs and symptoms (73%), often caused by
      subarachnoid hemorrhage (60%) and often leading to significant neurological
      deficits (47%). Initially, 14 of 15 patients (94%) were angiographically cured of
      their malformations. The remaining patient was neurologically improved after a
      90% resection, and follow-up angiography demonstrated that the residual was
      thrombosed. However, not uncommonly, follow-up angiography and magnetic resonance
      imaging revealed recurrences, with three of the patients who underwent delayed
      imaging (23%) demonstrating new draining veins. Fortunately, in each case, the
      recurrence was asymptomatic. Therefore, the long-term cure rate (mean follow-up,
      8.5 yr; range, 1-17 yr) was 80%, with no subsequent bleeding or progression of
      symptoms. Outcomes were generally good, with six patients (40%) demonstrating
      objective improvement, eight (53%) being neurologically stable, and one (7%)
      being worse. Sixty-six percent were independent, 20% required moderate
      assistance, and 14% remained entirely dependent. There were no deaths. Patients
      possessing lesions with large direct feeders off the anterior spinal artery and
      occupying a primarily anterior position in the cord fared somewhat worse, as did
      those with rapidly progressing symptomatology in the absence of subarachnoid
      hemorrhage. However, even in those with preserved or improved function, chronic
      pain was a significant problem, affecting one-third of all patients. Chronic pain
      was especially common in young women who had presented with significant
      preoperative pain that responded poorly to all subsequent therapeutic
      manipulations. CONCLUSION: With careful evaluation of high-quality superselective
      angiography and the judicious use of preoperative embolization, posterior
      surgical approaches can deliver results comparable with those achieved for other
      benign intramedullary lesions in terms of long-term cure (80%), control of
      symptom progression (100%), and good functional outcome (86%). Despite these
      results, chronic dysesthetic pain syndromes are not uncommon and continue to
      present a significant management problem.

PMID- 9574643
TI  - Cortical excitability of the biceps muscle after intercostal-to-musculocutaneous
      nerve transfer.
AB  - OBJECTIVE: Restoration of volitional control over elbow flexion has been
      demonstrated in patients who have undergone intercostal-to-musculocutaneous nerve
      transfer. We investigated the cortical area involved in the control over elbow
      flexion after intercostal-to-musculocutaneous nerve transfer. METHODS: Maps of
      magnetically excitable cortical areas of the affected arms of five patients were
      compared with maps of their healthy arms and maps of both arms of four healthy
      control subjects. The intercostal cortical area was also studied, requiring
      needle electromyography mapping (n = 1). RESULTS: The cortical areas of affected
      arms were smaller and less excitable than those of healthy arms. The locations of
      these areas could not be distinguished from that of the normal cortical biceps
      area but seemed to differ from that of the intercostal cortical area. CONCLUSION:
      The existence of a biceps-like cortical area related to the reinnervated muscle
      can be explained in two ways. Interneurons from the original biceps area might
      excite the cortical neurons controlling the intercostal muscles. Alternatively,
      corticospinal neurons of the original biceps area may project directly onto
      spinal intercostal motor neurons. Cerebral plasticity does occur in intercostal
      to-musculocutaneous nerve transfers and may be crucial for their clinical
      success.

PMID- 9574644
TI  - Surgical management of high-grade intracranial dural arteriovenous fistulas:
      leptomeningeal venous disruption without nidus excision.
AB  - OBJECTIVE: Of intracranial dural arteriovenous malformations (AVMs), those with
      cortical venous drainage pose the greatest risk of hemorrhaging. Given recent
      advances in endovascular, surgical, and radiosurgical techniques, the optimal
      management of these dural AVMs is controversial. For surgical candidates, the
      choice of intraoperative techniques remains unclear. Several authors have
      suggested that surgical clipping of the draining vein close to the nidus of dural
      AVMs can provide adequate treatment for some lesions. However, recent reports
      have also promoted partial or complete surgical resection of these lesions.
      METHODS: We present five cases of dural AVMs with cortical venous drainage that
      were surgically treated by the senior author between 1993 and 1996, and we review
      their management. Our series includes two frontal, one temporal, and two
      occipital lesions. Three patients presented with intracerebral hemorrhages, one
      with headache and eye pain, and one without symptoms. All five patients
      demonstrated venous aneurysms associated with the AVMs. Two patients underwent
      incomplete endovascular embolization before surgery. Operative management in all
      cases involved clipping of the draining vein as close as possible to the AVMs,
      together with extensive cautery of the surrounding dura. RESULTS: Postoperative
      angiography demonstrated complete angiographic obliteration in all cases. The
      four symptomatic patients all experienced clinical improvement postoperatively.
      The asymptomatic patient remained asymptomatic. With a mean follow-up period of
      29 months, no patient has developed recurrent symptoms. CONCLUSION: Surgical
      clipping of the draining vein close to dural AVMs has proven safe and effective
      in our experience. Given the highly vascular nature of dural AVMs, often near
      major dural sinuses, surgical resection of these lesions may not be indicated.

PMID- 9574645
TI  - Alignment correction algorithm for transformation of stereotactic anterior
      commissure/posterior commissure-based coordinates into frame coordinates for
      image-guided functional neurosurgery.
AB  - OBJECTIVE: The goal was to describe an alignment correction algorithm for the
      transformation of stereotactic atlas-derived anterior commissure/posterior
      commissure-based coordinates into frame coordinates for image-guided functional
      stereotactic neurosurgery. TECHNIQUE: The algorithm was developed for the
      calculation of targets that are referenced to the intercommissural line. It
      corrects for deviations of the axis of the intercommissural line in relation to
      the stereotactic frame (x, y, and z coordinates). The algorithm is easily
      implemented on a personal computer with a spreadsheet program. The calculation is
      fast and effective. CONCLUSION: The procedure is universally applicable for
      functional stereotactic neurosurgery, and it can be used with different
      stereotactic frames, different imaging techniques, and different workstations.

PMID- 9574646
TI  - Prevention of arachnoiditis and postoperative tethering of the spinal cord with
      Gore-Tex surgical membrane: an experimental study with rats.
AB  - OBJECTIVE: Arachnoidal adhesions and inflammation were evaluated in 72 rats after
      spinal dural repair with one of three materials, i.e., Gore-Tex surgical
      membrane, collagen-coated Vicryl mesh, or lyophilized spinal dural allograft.
      METHODS: Laminectomy at L1 was performed, and then a 3- x 4-mm segment of spinal
      dura mater and arachnoid membrane was excised. After implantation of the dural
      substitute, the animals were divided into normal and injured groups. In the
      injured group, a spinal cord injury was produced at the midpoint of the
      duraplasty site by the clip compression technique, with 25-g force for 1 minute.
      Neurological performance was assessed by the inclined plane technique, and groups
      of rats were killed at 8 to 24 weeks after surgery. The spinal column was removed
      en bloc and processed for histological examination. RESULTS: There were no
      differences in neurological function among the three dural substitutes in either
      injured or noninjured rats. However, there were major differences among the
      groups in the incidence and severity of arachnoid adhesions and tethering. The
      neural tissue was bound to a thick neomembrane surrounding the lyophilized dural
      allograft and the collagen-coated Vicryl mesh. In contrast, the Gore-Tex surgical
      membrane induced only a thin membranous adhesion, which was loose and flexible.
      The inflammatory and foreign body response was most pronounced in rats treated
      with collagen-coated Vicryl mesh, at 8 and 24 weeks. CONCLUSION: In the present
      study, Gore-Tex surgical membrane was a very good material for the surgical
      repair of spinal dural defects. Additional experimental studies are required to
      compare Gore-Tex membrane with autologous tissues.

PMID- 9574647
TI  - Adenosine triphosphate causes vasospasm of the rat femoral artery.
AB  - OBJECTIVE: Adenosine 5'-triphosphate (ATP) causes vasoconstriction by activation
      of P2-purinoceptors on vascular smooth muscle cells. Erythrocytes contain ATP at
      a concentration (1.6 mmol/L) that contracts smooth muscle. Previous studies of
      hemoglobin solutions did not assess whether the vasoactivity was caused by ATP
      rather than or in addition to hemoglobin. It was hypothesized that the hemolysis
      of erythrocytes that occurs after subarachnoid hemorrhage releases ATP in
      concentrations that cause vasospasm. METHODS: Thirty-eight rats were randomly
      assigned to undergo placement of one of the following compounds in a silastic
      elastomer cuff around each femoral artery: 1) agarose gel (n = 8); 2) dog
      erythrocyte hemolysate (n = 8); 3) purified human hemoglobin (Hemolink; Hemosol,
      Inc., Toronto, Canada; n = 8); 4) ATP (n = 8); or 5) clotted autologous blood (n
      = 6). The amounts of hemoglobins and adenine nucleotides in the compounds were
      measured by spectrophotometry and high pressure liquid chromatography.
      Hemolysate, purified hemoglobin, and ATP were mixed with agarose gel to create an
      artificial clot. Rats were killed and fixed by perfusion at physiological blood
      pressure 7 days after perivascular cuff and spasmogen placement. Vasospasm was
      assessed by image analysis of cross sections of fixed femoral arteries. Arteries
      were assessed for histopathological changes on 3-point scales. RESULTS: There was
      significant variance in arterial diameters among groups (mean diameter +/-
      standard deviation: agarose gel, 0.29 +/- 0.06; purified hemoglobin, 0.28 +/-
      0.04; hemolysate, 0.24 +/- 0.05; ATP, 0.25 +/- 0.05; clotted blood, 0.24 +/-
      0.01; P < 0.05, analysis of variance, n = 11-20). Animals exposed to clotted
      blood, hemolysate that contained ATP, or ATP, developed vasospasm, whereas
      purified hemoglobin and agarose did not cause vasospasm. Endothelial
      proliferation and perivascular inflammation were more severe (P < 0.05) in
      arteries exposed to clotted blood, purified hemoglobin, and hemolysate.
      CONCLUSION: These results suggest that ATP may be a vasospastic substance
      released by erythrocyte hemolysis. The concentration of ATP in impure solutions
      of hemoglobin is too low to account for the vasoactivity of these solutions. The
      discrepancy between arterial narrowing and histopathological changes suggests
      that either histopathological changes may not be an important correlate of
      arterial vasospasm or that other substances are important in vasospasm.

PMID- 9574648
TI  - Possible role of nitric oxide in autoregulatory response in rat intracerebral
      arterioles.
AB  - OBJECTIVE: Cerebral autoregulation is an important regulatory mechanism that
      maintains a constant cerebral blood flow over a wide range of perfusion
      pressures. The goal of this study was to determine whether nitric oxide
      contributes to the autoregulatory response of cerebral arterioles to altered
      transmural pressure (TMP). METHODS: Seventy-nine intraparenchymal arterioles
      (53.6 +/- 3.5 microm mean diameter) isolated from rats were cannulated with
      micropipettes and pressurized at a TMP of 60 mm Hg (control pressure). Vessel
      diameters were monitored continuously using a video dimensional analyzer. The
      autoregulatory diameter responses to varying intraluminal pressures were observed
      in the presence and absence of a nitric oxide synthase inhibitor, NG-monomethyl-L
      arginine (L-NMMA). The effect of L-NMMA-induced constriction on autoregulatory
      response also was compared with responses after prostaglandin F2alpha and
      alkalosis-induced constrictions. RESULTS: Autoregulatory responses were observed
      over a range from 10 to 90 mm Hg of TMP. Treatment with 10(-4) mol/L L-NMMA
      constricted arterioles and inhibited the autoregulatory vasodilation to TMP
      reductions from 60 mm Hg to 10 or 30 mm Hg. In L-NMMA-treated arterioles,
      elevation in TMP from 60 to 90 mm Hg caused an autoregulatory vasoconstriction.
      Treatment with alkaline pH 7.65 constricted arterioles to a similar degree as
      that induced by L-NMMA at 60 mm Hg, and under these conditions, the
      autoregulatory response remained intact. Arterioles severely constricted with
      prostaglandin F2alpha showed no significant autoregulatory response. CONCLUSION:
      These results suggest that 1) vascular nitric oxide release increases in response
      to a decrease in TMP from 60 mm Hg, thereby contributing to the autoregulatory
      vasodilation intrinsic to the vessel during hypotension, 2) arteriolar nitric
      oxide appears not to be involved in the autoregulatory vasoconstriction induced
      by elevating TMP from 60 to 90 mm Hg, and 3) a marked increase in vascular tone
      may affect autoregulatory response.

PMID- 9574649
TI  - Heat-induced apoptosis in human glioblastoma cell line A172.
AB  - OBJECTIVE: Hyperthermia has been clinically applied to some types of brain
      tumors. However, the detailed mechanisms of this growth inhibition are not clear.
      The effect of mild hyperthermia on cultured human glioblastoma cell line, A172,
      was studied. METHODS: A172 cells were heat treated (43-44.5 degrees C) for 1 hour
      in the growing phase. Cell viability was assessed by trypan blue dye exclusion
      assay. The presence of apoptosis was determined by the morphological changes
      observed using phase contrast microscopy and nuclear changes observed using
      HOECHST 33342 stain. For the evaluation of cellular deoxyribonucleic acid
      fragmentation, the TUNEL method was used. The expression of p53 and bax proteins
      was evaluated by Western blot, and the bax messenger ribonucleic acid was
      detected by Northern blot. RESULTS: Heat treatment induced cell death in time-
      and temperature-dependent manners. The nuclear staining with HOECHST 33342
      demonstrated morphological changes consistent with apoptosis. The TUNEL stain
      also demonstrated damages in the deoxyribonucleic acid. These morphological
      changes were accompanied by the accumulation of p53 protein, bax protein, and
      messenger ribonucleic acid. CONCLUSION: These results indicate that mild
      hyperthermia induces apoptosis in A172 glioblastoma cells.

PMID- 9574650
TI  - Interleukin-12-based immunotherapy against rat 9L glioma.
AB  - OBJECTIVE: Interleukin-12 (IL-12) may be useful for immunotherapy against gliomas
      because it can reverse the glioma-induced suppression of T-cell proliferation and
      interferon-gamma production. We postulated that peripheral infusion of IL-12
      along with irradiated tumor cells can lead to immunological rejection of 9L
      glioma. METHODS: 9L gliosarcoma flank tumors were established in syngeneic
      Fischer 344 rats. Osmotic minipumps delivered IL-12 subcutaneously, and
      irradiated 9L cells were injected on Days 0, 3, 7, 14, and 21. Tumor volumes were
      measured by a blinded observer. For tumor rechallenge, animals initially cured of
      9L flank tumors received either another implantation of flank tumor or a
      stereotactic injection of 10(6) 9L cells into the right striatum. Delayed-type
      hypersensitivity was measured after injecting 10(6) irradiated 9L tumor cells
      into the right pinnae. RESULTS: Tumor growth curves were significantly different
      between treated and control animals. Among the animals that received 1 ng per day
      of IL-12, 40% did not develop any measurable tumors at all. A combination of
      irradiated 9L cells and IL-12 was necessary for optimal effect. Cured animals
      rejected future flank tumors. All animals rechallenged with intraparenchymal
      brain tumors survived, whereas control animals all died by Day 22. Delayed-type
      hypersensitivity measurements showed a specific and long-lasting response against
      9L cells. CONCLUSION: Continuous administration of the lymphokine IL-12, in the
      presence of irradiated tumor cells for antigen presentation, circumvents the need
      for gene transfection for generating tumor cell vaccines. We have demonstrated
      that the combination of IL-12 and irradiated tumor cells can lead to regression
      of 9L flank tumors and resistance to future flank and central nervous system
      tumor challenges.

PMID- 9574651
TI  - Neural stem and progenitor cells: a strategy for gene therapy and brain repair.
AB  - The damaged adult mammalian brain is incapable of significant structural self
      repair. Although varying degrees of recovery from injury are possible, this is
      largely because of synaptic and functional plasticity rather than the frank
      regeneration of neural tissues. The lack of structural plasticity of the adult
      brain is partly because of its inability to generate new neurons, a limitation
      that has severely hindered the development of therapies for neurological injury
      or degeneration. However, a variety of experimental studies, as well as
      moderately successful clinical engraftment of fetal tissue into the adult
      parkinsonian brain, suggests that cell replacement is evolving as a valuable
      treatment modality. Neural stem cells, which are the self-renewing precursors of
      neurons and glia, have been isolated from both the embryonic and adult mammalian
      central nervous system. In the adult human brain, both neuronal and
      oligodendroglial precursors have been identified, and methods for their harvest
      and enrichment have been established. Neural precursors have several
      characteristics that make them ideal vectors for brain repair. They may be
      clonally expanded in tissue culture, providing a renewable supply of material for
      transplantation. Moreover, progenitors are ideal for genetic manipulation and may
      be engineered to express exogenous genes for neurotransmitters, neurotrophic
      factors, and metabolic enzymes. Thus, the persistence of neuronal precursors in
      the adult mammalian brain may permit us to design novel and effective strategies
      for central nervous system repair, by which we may yet challenge the
      irreparability of the structurally damaged adult nervous system.

PMID- 9574652
TI  - Microsurgical anatomy of the dural collar (carotid collar) and rings around the
      clinoid segment of the internal carotid artery.
AB  - OBJECTIVE: To examine the relationship of the clinoid segment of the internal
      carotid artery to the structures in the roof of the cavernous sinus and to
      determine whether this segment is neither intradural nor intracavernous, as
      recently proposed. METHODS: The region of the roof of the cavernous sinus was
      dissected and examined using 3 to 40x magnification and micro-operative
      techniques. RESULTS: The clinoid segment was located within a collar formed by
      the dura lining the medial surface of the anterior clinoid process, the posterior
      surface of the optic strut, and the upper part of the carotid sulcus. The clinoid
      segment and the collar were defined above by the upper ring formed by the dura
      extending medially from the upper surface of the anterior clinoid process to
      surround the artery and below by the lower ring formed by the dura extending
      medially from the lower surface of the anterior clinoid process. The upper ring
      was adherent to the wall of the artery, but the lower dural ring was separated
      from the lower margin of the clinoid segment by a narrow space that admitted
      venous tributaries of the cavernous sinus, called the clinoid venous plexus. This
      venous plexus narrowed as the upper ring was approached and became wider at the
      lower ring, where the plexus communicated with the venous channels of the
      cavernous sinus. The upper and lower dural rings were best defined along the
      lateral and anterior margins of the artery, were less distinct medially, and
      disappeared posteriorly, where the dura forming the upper and lower rings came
      together. CONCLUSION: The clinoid segment is intracavernous, being located within
      a collar of dura in which venous tributaries of the cavernous sinus course. The
      implications of these findings for surgery are reviewed.

PMID- 9574653
TI  - Silicone elastomer cerebrospinal fluid shunt systems. Council on Scientific
      Affairs, American Medical Association.
AB  - A 1995 resolution of the American Medical Association House of Delegates,
      introduced by the American Academy of Neurology, the American Association of
      Neurological Surgeons, and the Congress of Neurological Surgeons, asked the
      American Medical Association Council on Scientific Affairs to add the use of
      hardened silicone shunts to its study of the effects of silicone gel used in
      breast implants. On consideration of the important differences between the two
      materials, silicone elastomer ("hardened silicone") and silicone gel, the Council
      on Scientific Affairs elected to address the subject of silicone elastomer shunt
      systems separately. This report describes the different types of medical-grade
      silicone used in medical devices, the incidence of hydrocephalus and its causes
      and treatment, and the use of cerebrospinal fluid shunt systems made of silicone
      elastomer. Published case reports of possible immunological disease in patients
      who have had silicone elastomer cerebrospinal fluid shunt systems implanted are
      reviewed. The Council on Scientific Affairs concluded that the evidence presented
      does not support the occurrence of immune-mediated systemic reactions to
      implanted silicone elastomer cerebrospinal fluid shunt systems. The local
      granulomatous or inflammatory responses observed in some patients with silicone
      shunt systems have not been shown to be immunologically mediated; similar
      reactions have been described with other implanted foreign bodies.

PMID- 9574654
TI  - The origin and evolution of the University of Pittsburgh Department of
      Neurological Surgery.
AB  - Neurological surgery at the University of Pittsburgh began more than 60 years ago
      with the arrival of Stuart Niles Rowe. During the years, the department has been
      led by four men, each of whom guided the department into the future in his unique
      way. These men and many other dedicated physicians, nurses, and staff members
      have contributed to this organization and created an environment where
      neurosurgery flourishes. This article describes the development of neurosurgery
      within the "Steel City" and outlines the origin and growth of the Department of
      Neurological Surgery at The University of Pittsburgh Medical Center.

PMID- 9574655
TI  - History of the operating microscope: from magnifying glass to microneurosurgery.
AB  - The advent of the microscope in the operating room revolutionized neurosurgery.
      We traced the origin and evolution of this important invention from the first
      magnifying lens to its practical application in neurosurgery. The concept of
      magnification evolved from unexplained observations in ancient times to the
      invention of the microscope by the late 16th century. In the subsequent 3
      centuries, scientists made technical advances that greatly improved the power and
      utility of the microscope. By the early 20th century, otolaryngologists became
      the first surgeons to use the microscope in clinical surgery. After World War II,
      ophthalmologists and vascular and plastic surgeons began using the microscope in
      the operating room, making further technical improvements. It was a relatively
      small group of pioneering neurosurgeons in the late 1950s and 1960s who
      transformed microneurosurgery from a revolutionary and unorthodox "experiment"
      into the standard of care in much of modern neurosurgery.

PMID- 9574656
TI  - The contribution of Davide Giordano (1864-1954) to pituitary surgery: the
      transglabellar-nasal approach.
AB  - This report describes the fundamental contribution made by Davide Giordano,
      proposing the transglabellar surgical approach in a period in which transfacial
      and transbasal operative approaches to the pituitary gland were considered
      inadvisable because of their risk. His idea was to gain access through bilateral
      paranasal and frontal skin incisions, allowing removal of the ethmoid bone and
      the anterior wall of the sphenoidal cube. With the anterior and inferior aspects
      of the sella turcica thus exposed, bone is removed and the gland is exposed by
      incision of the dura mater. The technique proposed by Giordano is undoubtedly a
      forerunner of the transsphenoidal route to the pituitary gland. The importance of
      his contribution was confirmed by Cushing, who reported his first use of the
      approach of Giordano in 1909 in a patient with a pituitary adenoma. The efforts
      of Giordano clearly inspired surgeons of his era to perform this operation
      clinically, giving impetus to the further development of neurosurgery.

PMID- 9574657
TI  - Giant pituitary prolactinoma with falsely low serum prolactin: the pitfall of the
      "high-dose hook effect": case report.
AB  - OBJECTIVE AND IMPORTANCE: We present a case of a giant prolactinoma with a
      falsely low serum prolactin concentration determined by a two-site
      chemiluminometric assay. Awareness of the possibility of the "high-dose hook
      effect" in such cases will prevent preoperative misdiagnosis. CLINICAL
      PRESENTATION: A patient with a giant invasive pituitary tumor was found
      preoperatively to have serum prolactin of 31 ng/ml. Pathological examination of
      the excised tissue, however, demonstrated strong staining for prolactin.
      INTERVENTION: Serial dilutions of the serum disclosed hyperprolactinemia of
      280,000 ng/ml, establishing the presence of the "high-dose hook effect."
      Treatment with pergolide (Permax; Athena Neurosciences, S. San Francisco, CA)
      decreased tumor size and lowered serum prolactin by more than 99%. CONCLUSION: A
      "high-dose hook effect" needs to be suspected in every patient with a giant
      pituitary adenoma (>3 cm) and normal serum prolactin. Subsequently assaying the
      diluted serum will reliably disclose this phenomenon and allow correct diagnosis
      and therapy.

PMID- 9574658
TI  - The syndrome of inappropriate secretion of antidiuretic hormone: an unusual
      presentation for childhood craniopharyngioma: report of three cases.
AB  - OBJECTIVE AND IMPORTANCE: Childhood craniopharyngiomas may present with variable
      endocrine dysfunctions. However, hyponatremia secondary to the syndrome of
      inappropriate secretion of antidiuretic hormone has never been reported. We
      describe three children with craniopharyngioma who presented with hyponatremia.
      CLINICAL PRESENTATION: Three children had hyponatremia at presentation, two of
      whom had experienced generalized seizures. Urine sodium levels measured in two
      patients were abnormally high. Neuroimaging tests, including computed tomography
      and magnetic resonance imaging, showed a large partially calcified and partially
      cystic craniopharyngioma in the sellar/suprasellar location. INTERVENTION: Intake
      of fluids was restricted for each patient, with improvement of hyponatremia, and
      each patient subsequently underwent a successful tumor resection.
      Postoperatively, all patients developed panhypopituitarism, including diabetes
      insipidus, and needed multiple hormonal replacement therapy. CONCLUSION:
      Endocrine dysfunctions at diagnosis are commonly associated with childhood
      craniopharyngiomas, but the association of the syndrome of inappropriate
      secretion of antidiuretic hormone with craniopharyngioma has never been reported.
      Craniopharyngiomas should be included as a possibility in making the differential
      diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone in
      children.

PMID- 9574659
TI  - Visual failure caused by suprasellar extramedullary hematopoiesis in beta
      thalassemia: case report.
AB  - OBJECTIVE AND IMPORTANCE: Small deposits of extramedullary hematopoiesis, acting
      as epileptogenic foci, have been observed near convexity dura and adjacent to
      falx cerebri. These foci could potentially grow and act as space-occupying
      lesions, producing focal neurological deficits. This condition was observed in a
      unique case of thalassemia major, with progressive visual loss caused by
      extramedullary hematopoiesis originating from the base of the cranium and
      extending up to the inferior third ventricle. The patient had been operated on 4
      years earlier to relieve the compressive effects of ectopic marrow in the
      thoracolumbar epidural space. CLINICAL PRESENTATION: A 21-year-old man is
      reported with progressive visual loss caused by compressive optic neuropathy as a
      result of extramedullary hematopoiesis. Computed tomography of the head revealed
      a suprasellar and parasellar enhancing mass originating from the pre-sphenoid
      cranial base and approaching the lower third ventricle. INTERVENTION: Partial
      resection of the tumor was accomplished by a transsphenoidal approach. Monthly
      blood transfusions and low-dose radiotherapy of the appropriate anatomic
      structures were then performed. The patient's visual acuity improved only
      modestly. CONCLUSION: Extramedullary hematopoiesis, although extremely rare,
      could arise from the base of the cranium and act as a parasellar tumor. When any
      patient with thalassemia major requiring multiple transfusions develops visual
      failure, appropriate studies should be performed to rule out compression of
      visual pathways by ectopic marrow, especially if the patient is receiving
      deferoxamine.

PMID- 9574660
TI  - Endolymphatic sac tumors: report of three cases.
AB  - OBJECTIVE AND IMPORTANCE: We present three cases of endolymphatic sac tumors and
      review the previously published cases. Despite frequent extension to the
      cerebellopontine angle, these rare tumors have only recently been recognized by
      neurosurgeons. CLINICAL PRESENTATION: A 26-year-old man developed a progressive
      hearing loss, revealing an intrapetrous retrolabyrinthine tumor on the right
      side. A 28-year-old woman experienced a left cerebellopontine angle syndrome,
      with a lytic intrapetrous mass extending into the cerebellopontine angle. A 38
      year-old woman presented with an intracranial hypertension syndrome caused by a
      tumor of the jugular foramen. INTERVENTION: For the first and second patients,
      the tumors originated from the operculum of the endolymphatic sac. Total removal
      was achieved, via a transpetrosal approach, in these two cases. No recurrence was
      detected after a 20-month follow-up period. For the third patient, the tumor
      originated from the distal part of the sac. Recurrence was observed 8 years after
      subtotal removal via a retrosigmoid route. Histological analysis revealed a
      papillary-cystic adenocarcinomatous pattern in all cases, without features of
      aggressiveness. CONCLUSION: Endolymphatic sac tumors are locally invasive
      neoplasms characterized by bipolar intrapetrous and posterior fossa involvement.
      The anatomic complexity of the endolymphatic sac may explain the distinct
      patterns of extension of these tumors. Early radical surgery is related to good
      outcomes.

PMID- 9574661
TI  - Mycosis fungoides metastasizing to the brain parenchyma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Mycosis fungoides is a rare T-cell lymphoma of the skin
      that can, in one-half to three-quarters of patients suffering from this disease,
      involve the viscera in late stages of the disease. Although autopsy series
      performed more than 2 decades ago showed that the incidence of metastatic mycosis
      fungoides to the central nervous system is approximately one of seven, a total of
      only several dozen cases have been reported to date. As compared to meningeal
      involvement, intraparenchymal metastases are even rarer. We describe a biopsy
      proven case of intraparenchymal central nervous system mycosis fungoides in a
      patient with nonprogressive skin involvement and no detectable visceral
      involvement, and we present a review of the relevant literature. CLINICAL
      PRESENTATION: A 68-year-old man, 3 years after the diagnosis of his skin disease,
      developed fatigue, confusion, and frontal lobe signs without the presence of
      cerebriform cells in the peripheral blood or any other clinical evidence of
      visceral involvement. Magnetic resonance imaging revealed a diffuse area of
      increased T2-weighted signal involving the white matter of both cerebral
      hemispheres as well as a focal area of T2 abnormality along the body of the
      corpus callosum. The radiological differential diagnosis was either
      leukodystrophy caused by chemotherapy, progressive multifocal
      leukoencephalopathy, or glioma with associated white matter changes.
      INTERVENTION: A stereotactic serial brain biopsy revealed diffuse perivascular
      infiltrates of atypical lymphocytes, as well as several large cells with
      cerebriform nuclei consistent with mycosis fungoides. The cells were
      immunoreactive for LCA, MT1, UCHL1, and CD3. CONCLUSION: We stress the importance
      of including mycosis fungoides as part of the differential diagnosis for a brain
      lesion in patients with cutaneous T-cell lymphoma, because treatments do exist,
      and we conclude that a serial stereotactic biopsy may be necessary to provide a
      definitive diagnosis.

PMID- 9574662
TI  - Bilateral (mirror-image) aneurysms at the origin of the posteroinferior
      cerebellar artery: case report.
AB  - OBJECTIVE AND IMPORTANCE: This case demonstrates mirror-image aneurysms at the
      origin of the posteroinferior cerebellar arteries. To the best of our knowledge,
      this location has not been previously described. Identification of this entity is
      important for surgical planning. CLINICAL PRESENTATION: The patient presented
      with a history of a sentinel headache 1 week before his Grade I subarachnoid
      hemorrhage occurred. Before operative intervention, the patient developed acute
      deterioration of his mental status from hydrocephalus. After appropriate
      treatment for the hydrocephalus, he maintained a stable neurological course
      throughout evaluation and therapy. INTERVENTION: The patient underwent bilateral
      clipping of his aneurysms in a prone position without consequence. CONCLUSION:
      This case demonstrates a highly unusual mirror-image aneurysm of the proximal
      posteroinferior cerebellar arteries. Although multiple aneurysms are commonplace,
      to the best of our knowledge, this is the first reported case of bilateral
      posteroinferior cerebellar artery aneurysms at their origin. Also, the surgical
      approach is unique and allows bilateral clipping at the same operative setting.

PMID- 9574664
TI  - Studies in neurology. 1920. Aphasia and kindred disorders of speech. 1926.

PMID- 9574663
TI  - Intraoperative color-coded duplex sonography for localization of a distal middle
      cerebral artery aneurysm: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: We describe the surgical treatment of a small, distal,
      middle cerebral artery (MCA) aneurysm, performed using intraoperative color-coded
      duplex sonography for localization. CLINICAL PRESENTATION: A 55-year-old man
      presented with a sudden intense headache. Computed tomographic scans revealed a
      subarachnoid hemorrhage. Angiography demonstrated two MCA aneurysms, one arising
      from the proximal bifurcation of the right MCA and the other from its distal
      bifurcation. TECHNIQUE: On Day 1, the proximal MCA aneurysm was clipped via the
      standard transsylvian approach. The distal MCA aneurysm was identified with the
      aid of color-coded duplex sonography and was successfully clipped with minimal
      additional dissection of the sylvian fissure. CONCLUSION: Color-coded duplex
      sonography provides a two-dimensional image of the brain parenchyma and color
      coded flow imaging of cerebral vessels in real time. It may be used for rapid
      intraoperative localization of small, distally located, cerebral aneurysms.

PMID- 9574665
TI  - Intraoperative dislocation of the distal lens of a neuroendoscope: a very rare
      complication: technical case report.

PMID- 9574666
TI  - Determining the best cerebrospinal fluid shunt valve design: the pediatric valve
      design trial.

PMID- 9574667
TI  - Complications in patients with palmar hyperhidrosis treated with transthoracic
      endoscopic sympathectomy.

PMID- 9574668
TI  - Lumbar cerebrospinal fluid drainage for symptomatic sacral nerve root cysts: an
      adjuvant diagnostic procedure and/or alternative treatment? Technical case
      report.

PMID- 9574669
TI  - Neurosurgery and the Internet: a critical analysis and a review of available
      resources.

PMID- 9574670
TI  - Panfungal PCR assay for detection of fungal infection in human blood specimens.
AB  - A novel panfungal PCR assay which detects the small-subunit rRNA gene sequence of
      the two major fungal organism groups was used to test whole-blood specimens
      obtained from a series of blood or bone marrow transplant recipients. The 580-bp
      PCR product was identified after amplification by panfungal primers and
      hybridization to a 245-bp digoxigenin-labeled probe. The lower limit of detection
      of the assay was approximately four organisms per milliliter of blood. Multiple
      whole-blood specimens from five patients without fungal infection or colonization
      had negative PCR results. Specimens from 11 infected patients had positive PCR
      results. Blood from three patients with pulmonary aspergillosis had positive PCR
      results: one patient's blood specimen obtained in the week prior to the diagnosis
      of infection by a positive bronchoalveolar lavage fluid culture result was
      positive by PCR, and blood specimens obtained from two patients 1 to 2 days after
      lung biopsy and which were sterile by culture were positive by PCR. The blood of
      four patients with candidemia, three patients with mixed fungal infections, and
      one patient with fusariosis also had positive PCR signals. The panfungal PCR
      assay can detect multiple fungal genera and may be used as an adjunct to
      conventional methods for the detection of fungal infection or for describing the
      natural history of fungal infection. Further studies are needed to define the
      sensitivity and specificity of this assay for the diagnosis of fungal infection
      prior to the existence of other clinical or laboratory indications of invasive
      fungal infection.

PMID- 9574671
TI  - Evaluation of BACTEC MYCO/F lytic medium for recovery of mycobacteria and fungi
      from blood.
AB  - The reliability of MYCO/F Lytic medium in the BACTEC 9240 blood culture system
      was evaluated by comparing its performance to that of the Isolator system for the
      recovery of fungi and to that of the ESP II system for the recovery of
      mycobacteria. Of 717 specimens of blood cultured for fungi, 24 were positive; 12
      samples were positive with both systems, 7 samples were positive with the
      Isolator system only, and 5 samples were positive with MYCO/F Lytic medium only.
      Fourteen samples grew Histoplasma capsulatum; both systems detected H. capsulatum
      in seven samples but the Isolator system alone detected H. capsulatum in seven
      samples. The mean times to the detection of H. capsulatum were 8 days (range, 4
      to 13 days) for MYCO/F Lytic medium and 9 days (range, 6 to 18 days) for the
      Isolator system; the mean times to identification were 20 days (range, 15 to 24
      days) for isolates recovered with MYCO/F Lytic medium and 11 days (range, 6 to 18
      days) for those recovered with the Isolator system (P < 0.05). Cryptococcus
      neoformans was isolated from 10 fungal cultures; five isolates grew in both
      systems, and five isolates grew in MYCO/F Lytic medium only. The mean times to
      detection of C. neoformans were 4 days (range, 2 to 6 days) for MYCO/F Lytic
      medium and 7 days (range, 5 to 7 days) for the Isolator system (P < 0.05); the
      mean times to identification were 15 days (range, 7 to 27 days) for isolates
      recovered with MYCO/F Lytic medium and 8 days (range, 7 to 11 days) for those
      recovered with the Isolator system. Of the 687 samples of blood cultured for
      mycobacteria, 64 blood samples from 42 patients grew mycobacteria (58 grew
      Mycobacterium avium complex, 4 grew Mycobacterium kansasii, and 2 grew
      Mycobacterium tuberculosis); 42 isolates were recovered with both systems, 18
      were isolated with MYCO/F medium only, and 4 were isolated with the ESP II system
      only alone (P < 0.05). The mean time to detection of mycobacteria with MYCO/F
      Lytic medium was 14 days, whereas it was 17 days with the ESP II system (P <
      0.05). In summary, the combination of MYCO/F Lytic medium and the BACTEC 9240
      instrument is an excellent blood culture system for the growth and detection of
      mycobacteria. A valid assessment of MYCO/F Lytic medium with regard to fungal
      isolation, however, was not possible due to the small number of isolates
      recovered.

PMID- 9574672
TI  - Insertion element IS3-based PCR method for subtyping Escherichia coli O157:H7.
AB  - An Escherichia coli O157:H7 subtyping method based on PCR amplification of
      variable DNA sequences between the repetitive element IS3 was developed. Template
      DNA was prepared by boiling cells in Chelex. Two separate IS3 PCR amplifications
      were performed for each isolate: one with a single primer (primer IS3A) and one
      with two primers (primers IS3A and IS3B). The IS3 PCR subtyping method was
      applied to 35 epidemiologically related and unrelated E. coli O157:H7 isolates
      that had been previously characterized by pulsed-field gel electrophoresis
      (PFGE). PFGE identified 25 different subtypes (difference of one or more bands).
      PCR with single primer IS3A and primer pair IS3A-IS3B identified 6 and 14
      different subtypes, respectively. By combining the results of the two PCR
      amplifications, 15 different IS3 PCR subtypes were identified. While not as
      sensitive as PFGE, IS3 PCR subtyping grouped all outbreak-related isolates. IS3
      PCR banding patterns were reproducible between amplifications and between
      subcultures. IS3 PCR could serve as a simple, rapid screening method for the
      identification of unrelated E. coli O157:H7 isolates.

PMID- 9574673
TI  - Two-step PCR-based assay for identification of bacterial etiology of otitis media
      with effusion in infected Lebanese children.
AB  - We developed and evaluated a two-step PCR-based assay with universal primers and
      genus- or species-specific primers for the detection of the most prevalent
      bacterial etiologies of otitis media with effusion (OME) in children from
      Lebanese hospitals. These etiologies included Haemophilus, Streptococcus, and
      Moraxella (Branhamella) catarrhalis, which were detected in middle-ear effusion
      (MEE) samples taken from children with OME. A total of 47 MEE samples were
      aspirated from 36 patients during insertion of a tympanostomy tube performed
      particularly for OME. The duration of effusion in all patients was > or =2
      months. DNA was extracted from MEE samples, and PCR was initially done with DNA
      extracts by using the universal primers RW01 and DG74, which flank an
      approximately 370-bp fragment found in the 16S rRNA gene of all bacterial
      species. For the identification of specific bacteria, we used in three separate
      reaction mixtures the following genus- or species-specific primers: (i) a
      Haemophilus-specific probe (probe RDR125) as a primer along with DG74, (ii) a
      Streptococcus-specific primer (primer STR1; designed by us) along with DG74, and
      (iii) an M. catarrhalis-specific primer pair (primer pair MCA1-MCA2). Thirty-five
      MEE samples (74.5%) gave the expected 370-bp band, indicating the presence of
      bacterial DNA in the tested samples. Of the 35 PCR-positive samples tested, 33
      (94.3%) were positive for Haemophilus, 3 (8.6%) were positive for Streptococcus,
      and 10 (28.6%) were positive for M. catarrhalis. Ten samples (28.6%) exhibited a
      mixed infection and were positive for both Haemophilus and M. catarrhalis.
      Culture was simultaneously performed for all 47 MEE samples. Ten of the 47 MEE
      samples (21.3%) exhibited bacterial growth. These 10 were PCR positive for
      bacterial DNA. The remaining 25 PCR-positive samples were negative by culture,
      thus showing about 53% discordance between PCR results and those of culture. The
      PCR assay proved to be more sensitive than culture, more rapid, less cumbersome,
      and more cost-effective than the available PCR-Southern hybridization-based
      assays.

PMID- 9574674
TI  - Immunoglobulin A-specific capture enzyme-linked immunosorbent assay for diagnosis
      of dengue fever.
AB  - Dengue fever (DF) is usually diagnosed by testing for dengue virus immunoglobulin
      M (IgM) by a capture enzyme-linked immunosorbent assay (ELISA) (MAC-ELISA).
      However, IgM can last for months, and its presence might reflect a previous
      infection. We have tested the use of anti-dengue virus IgA capture ELISA (AAC
      ELISA) for the diagnosis of DF by comparing the results of MAC-ELISAs and AAC
      ELISAs for 178 serum samples taken from patients with confirmed cases of DF. IgM
      appears more rapidly (mean delay of positivity, 3.8 days after the onset of DF)
      than IgA (4.6 days) but lasts longer; the peak IgA titer is obtained on day 8.
      The specificity and the positive predictive value of AAC-ELISA are 100%; its
      sensitivity and negative predictive value (NPV) are also 100% between days 6 and
      25 after the onset of DF, but they decrease drastically when data for tests
      conducted with specimens from the first days of infection are included, because
      the IgA titers, like the IgM titers, have not yet risen. AAC-ELISA is a simple
      method that can be performed together with MAC-ELISA and that can help in
      interpreting DF serology.

PMID- 9574675
TI  - Short-term follow-up by serology of patients given antibiotic treatment for
      Helicobacter pylori infection.
AB  - Helicobacter pylori serology and in particular enzyme-linked immunosorbent assays
      for the measurement of immunoglobulin G (IgG) antibody titers form an accurate
      means of diagnosing H. pylori infection in patients before treatment. H. pylori
      serology is of limited value in monitoring treatment because of the slow decline
      in antibody titers. In the present study we aimed to measure the most suitable
      moment after antibiotic treatment at which serology should be used to monitor
      treatment. Sixty-four patients who had nonulcer dyspepsia and H. pylori infection
      and who underwent upper gastrointestinal endoscopy because of persistent
      dyspeptic symptoms were included in the study. H. pylori cure was confirmed by
      histology and culture 5 weeks after the completion of the antibiotic treatment.
      Serological examination was performed before therapy and at 5 weeks, 10 weeks,
      and 1 year after the completion of antibiotic treatment. Diagnostic performance
      was assessed by receiver-operating characteristic analysis. The areas under the
      receiver-operating characteristic curves of the H. pylori antibody titers at 5
      weeks, 10 weeks, and 1 year after the completion of treatment were 0.53 (95%
      confidence interval [CI], 0.36 to 0.69), 0.60 (95% CI, 0.43 to 0.76), and 0.78
      (95% CI, 0.63 to 0.93), respectively. The areas under the receiver-operating
      characteristic curves of the changes in H. pylori IgG antibody titers at 5 weeks,
      10 weeks, and 1 year after the completion of treatment in comparison with the
      pretreatment titers were 0.85 (95% CI, 0.72 to 0.97), 0.96 (95% CI, 0.89 to 1.0),
      and 1.0 (95% CI, not estimable), respectively. We conclude that serology forms a
      useful means of monitoring treatment in patients with nonulcer dyspepsia and H.
      pylori infection as early as 10 weeks and maybe even sooner after the completion
      of treatment for the infection.

PMID- 9574676
TI  - Limitations of the current microbial identification system for identification of
      clinical yeast isolates.
AB  - The ability of the rapid, computerized Microbial Identification System (MIS;
      Microbial ID, Inc.) to identify a variety of clinical isolates of yeast species
      was compared to the abilities of a combination of tests including the Yeast
      Biochemical Card (bioMerieux Vitek), determination of microscopic morphology on
      cornmeal agar with Tween 80, and when necessary, conventional biochemical tests
      and/or the API 20C Aux system (bioMerieux Vitek) to identify the same yeast
      isolates. The MIS chromatographically analyzes cellular fatty acids and compares
      the results with the fatty acid profiles in its database. Yeast isolates were
      subcultured onto Sabouraud dextrose agar and were incubated at 28 degrees C for
      24 h. The resulting colonies were saponified, methylated, extracted, and
      chromatographically analyzed (by version 3.8 of the MIS YSTCLN database)
      according to the manufacturer's instructions. Of 477 isolates of 23 species
      tested, 448 (94%) were given species names by the MIS and 29 (6%) were
      unidentified (specified as "no match" by the MIS). Of the 448 isolates given
      names by the MIS, only 335 (75%) of the identifications were correct to the
      species level. While the MIS correctly identified only 102 (82%) of 124 isolates
      of Candida glabrata, the predictive value of an MIS identification of unknown
      isolates as C. glabrata was 100% (102 of 102) because no isolates of other
      species were misidentified as C. glabrata. In contrast, while the MIS correctly
      identified 100% (15 of 15) of the isolates of Saccharomyces cerevisiae, the
      predictive value of an MIS identification of unknown isolates as S. cerevisiae
      was only 47% (15 of 32), because 17 isolates of C. glabrata were misidentified as
      S. cerevisiae. The low predictive values for accuracy associated with MIS
      identifications for most of the remaining yeast species indicate that the
      procedure and/or database for the system need to be improved.

PMID- 9574678
TI  - Three cases of Anaerobiospirillum succiniciproducens bacteremia confirmed by 16S
      rRNA gene sequencing.
AB  - We describe three cases of Anaerobiospirillum succiniciproducens bacteremia from
      Australia. We believe one of these cases represents the first report of A.
      succiniciproducens bacteremia in a human immunodeficiency virus (HIV)-infected
      individual. The other two patients had an underlying disorder (one patient had
      bleeding esophageal varices complicating alcohol liver disease and one patient
      had non-Hodgkin's lymphoma). A motile, gram-negative, spiral anaerobe was
      isolated by culturing blood from all patients. Electron microscopy showed a
      curved bacterium with bipolar tufts of flagella resembling Anaerobiospirillum
      spp. Sequencing of the 16S rRNA genes of the isolates revealed no close relatives
      (organisms likely to be in the same genus) in the sequence databases, nor were
      any sequence data available forA. succiniciproducens. This report presents for
      the first time the 16S rRNA gene sequence of the type strain of A.
      succiniciproducens, strain ATCC 29305. Two of the three clinical isolates have
      sequences identical to that of the type strain, while the sequence of the other
      strain differs from that of the type strain at 4 nucleotides.

PMID- 9574677
TI  - Ultrastructure, immunofluorescence, western blot, and PCR analysis of eight
      isolates of Encephalitozoon (Septata) intestinalis established in culture from
      sputum and urine samples and duodenal aspirates of five patients with AIDS.
AB  - Microsporidia are ancient, intracellular, eukaryotic protozoan parasites that
      form spores and that lack mitochondria. Currently, as many as eight species
      included under six genera are known to infect humans, mostly patients with AIDS.
      Among these, Enterocytozoon bieneusi, the agent of gastrointestinal (GI) disease,
      is the most frequently identified microsporidian in clinical laboratories in the
      United States. Encephalitozoon (Septata) intestinalis, the agent that causes a
      disseminated infection including infection of the GI tract, is the second most
      frequently identified microsporidian parasite. In spite of this, not many
      isolates of E. intestinalis have been established in culture. We describe here
      the continuous cultivation of eight isolates of E. intestinalis obtained from
      different samples including the urine, sputum, and duodenal aspirate or biopsy
      specimens from five AIDS patients originating from California, Colorado, and
      Georgia. The specific identification was made on the bases of ultrastructural,
      antigenic, and PCR analyses.

PMID- 9574679
TI  - Use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide for rapid
      detection of rifampin-resistant Mycobacterium tuberculosis.
AB  - We describe a test which uses the ability of viable cells to reduce 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to detect resistance
      to a bactericidal drug, rifampin, in in vitro-cultured Mycobacterium
      tuberculosis. The assay shows a linear relationship between the number of viable
      bacteria and the ability to reduce MTT. Dead mycobacteria were unable to reduce
      MTT. Rifampin-sensitive M. bovis (BCG) and M. tuberculosis exposed to rifampin
      showed a rifampin concentration-dependent inhibition of the ability to reduce
      MTT, while the resistant strains were unaffected. The inhibition of MTT reduction
      after treatment with rifampin paralleled the reduction in the number of CFU. By
      using mixing experiments in which the population percentages of rifampin
      sensitive and -resistant strains were varied, the assay could detect the presence
      of rifampin resistance in the mixture when at least 1% of the bacterial
      population was composed of drug-resistant strains. The assay is cheap, can be
      visually read, and requires less than 3 days to obtain susceptibility results.
      The total time required to obtain results, from the time sputum is received in
      the laboratory, is, in most cases, less than 4 to 5 weeks, which is the time
      required for primary culture of the bacteria. The MTT assay could, in combination
      with a test to detect resistance to isoniazid, be a cheap and rapid screening
      method for multidrug-resistant M. tuberculosis that is affordable even by low
      income countries where tuberculosis is a major public health problem.

PMID- 9574680
TI  - Detection of kanamycin-resistant Mycobacterium tuberculosis by identifying
      mutations in the 16S rRNA gene.
AB  - In Mycobacterium smegmatis and a limited number of Mycobacterium tuberculosis
      strains, the involvement of alterations of the 16S rRNA gene (rrs) in resistance
      to kanamycin has been shown. To investigate the extent to which mutations in a
      specific region of the rrs gene and the kanamycin-resistant phenotype in
      clinically isolated M. tuberculosis strains were correlated, 43 kanamycin
      resistant strains (MICs, > or =200 microg/ml), 71 kanamycin-susceptible strains,
      and 4 type strains were examined. The 300-bp DNA fragments carrying the rrs gene
      and the intervening sequence between the rrs gene and 23S rRNA (rrl) gene
      fragments were amplified by PCR and were subjected to PCR-based direct
      sequencing. By comparing the nucleotide sequences, substitutions were found in 29
      of 43 (67.4%) kanamycin-resistant clinical isolates at positions 1400, 1401, and
      1483 but in none of the 71 sensitive isolates or the 4 type strains. The most
      frequent substitution, from A to G, occurred at position 1400. A substitution
      from C to T at position 1401 was found once. Two clinical isolates carried the
      double mutation from C to A at position 1401 and from G to T at position 1483. In
      addition, we found that these mutants can be distinguished from wild-type strains
      by digestion with the restriction endonucleases TaiI and Tsp45I. Furthermore, we
      found that the genotypes of kanamycin-resistant strains can be discriminated from
      each other by digestion with a restriction endonuclease, BstUI or DdeI.

PMID- 9574681
TI  - Genotypic characterization of seven strains of Mycoplasma fermentans isolated
      from synovial fluids of patients with arthritis.
AB  - We performed a genotypic characterization of seven strains of Mycoplasma
      fermentans which have been isolated from the synovial fluid of patients with
      rheumatoid arthritis (n = 2), spondyloarthropathy (n = 1), and unclassified
      arthritis (n = 4). We compared them to three reference strains (strains PG18 and
      K7 and incognitus strain) and to a clinical isolate from the urethra of a patient
      with nongonococcal urethritis. The characterization methods included
      electrophoresis of native DNA, arbitrarily primed PCR, and restriction fragment
      length polymorphism analysis following conventional and pulsed-field gel
      electrophoresis. Southern blot analysis with a probe internal to an insertion
      sequence was performed with the restriction products produced by the last two
      techniques. No extrachromosomal DNA sequences were detected. The M. fermentans
      strains identified by these methods did not present a unique profile, but they
      could be separated into two main categories: four articular isolates were
      genetically related to PG18 and the three other isolates, the urethral isolate,
      and the incognitus strain were related to K7. We also looked for the presence of
      the bacteriophage MAV1 (associated with the arthritogenic property of Mycoplasma
      arthritidis in rodents) in the M. fermentans strains. MAV1 DNA was not detected
      in either the clinical isolates or the reference strains of M. fermentans.

PMID- 9574682
TI  - Growth and survival of Helicobacter pylori in defined medium and susceptibility
      to Brij 78.
AB  - The gastrointestinal pathogen Helicobacter pylori requires supplementation with
      either fetal calf serum (FCS), bovine serum albumin (BSA), or (2,6-dimethyl)-beta
      cyclodextrin (CD) for growth in a complex or defined medium. Because the
      availability of medium in which all components were chemically defined would
      facilitate metabolic studies of H. pylori, growth of the type strain, ATCC 43504,
      was compared in a defined medium with different growth additives. The dependency
      of H. pylori growth on FCS or BSA in a defined medium could partially be replaced
      by dependency on CD and cholesterol when the last two components were both added
      to the defined medium. Growth and cell yield were not affected by the addition of
      glucose, but the culture viability (numbers of CFU per milliliter was extended.
      Because therapeutic antifoams are used to relieve gastrointestinal symptoms we
      studied whether the unique susceptibility of H. pylori to the emulsifier
      polyoxyethylene-20-stearylether (Brij 78) was growth dependent or medium
      specific. The bactericidal activity exerted in buffer at pH 5 was independent of
      the preculture medium, and a 5-h exposure of the bacteria to 1.28 to 2.56 microg
      of Brij 78 per ml reduced the numbers of viable bacteria by >5 log10. The MICs
      (0.16 to 0.32 microg/ml) were lower than the corresponding minimal bactericidal
      concentrations in different growth media and were affected by FCS or BSA. In
      conclusion, CD plus cholesterol promotes the growth of H. pylori in a serum-free
      defined medium in which glucose enhances cell viability. The antibacterial
      activity exerted by Brij 78 is neither growth dependent nor medium specific.

PMID- 9574683
TI  - Detection of Ureaplasma urealyticum in endotracheal tube aspirates from neonates
      by PCR.
AB  - A PCR-based test was optimized for the detection of Ureaplasma urealyticum from
      neonatal respiratory specimens, with primers directed against the multiple-banded
      antigen gene (L. J. Teng, X. Zheng, J. I. Glass, H. Watson, J. Tsai, and G. H.
      Cassell, J. Clin. Microbiol. 32:1464-1469, 1994). Endotracheal tube aspirates
      (225) from 103 low-birth-weight neonates (<1,250 g) were taken, when possible, at
      days 0, 4, and 14 after birth and examined by culture and by PCR. Of 77 specimens
      positive by either method, 73 were detected by PCR and 60 were detected by
      culture. Overall, 36% of the neonates were positive for U. urealyticum by either
      method. Of 16 patients with PCR-positive-culture-negative results, 13 had
      positive cultures at another sampling point, and one additional patient had a
      twin with positive cultures. Of 11 patients with day 0 specimens positive by PCR
      alone, 9 subsequently became culture positive, demonstrating the utility of this
      test in early detection. Multiple serovars were present in over 50% of positive
      specimens, with serovars 3 and 14 in combination being most prevalent. The
      amplicon size generated from the specimen by PCR correctly predicted the biovars
      isolated in over 85% of positive specimens. Thus, this PCR test was valuable in
      allowing early detection of U. urealyticum in neonatal respiratory specimens, as
      well as in providing biovar information.

PMID- 9574684
TI  - Temporal correlations between tick abundance and prevalence of ticks infected
      with Borrelia burgdorferi and increasing incidence of Lyme disease.
AB  - The abundance of host-seeking Ixodes scapularis nymphs, the principal vector for
      the Lyme disease agent, Borrelia burgdorferi, in Old Lyme, Lyme, and East Haddam,
      Connecticut, was compared with the incidence of reported human Lyme disease in
      the 12-town area around the Connecticut River and the State of Connecticut for
      the period 1989 to 1996. Ticks were sampled from lawns and woodlands by dragging
      flannel over the vegetation and examined for the presence of B. burgdorferi by
      indirect fluorescent antibody staining. The infection rate of the nymphal ticks
      by B. burgdorferi during the 9-year period was 14.3% (of 3,866), ranging from
      8.6% (1993) to 24.4% (1996). The incidence of Lyme disease was positively
      correlated with tick abundance in the 12 town area (r = 0.828) and the State of
      Connecticut (r = 0.741). An entomological risk index based upon the number of I.
      scapularis ticks infected by B. burgdorferi was highest in 1992, 1994, and 1996
      and was highly correlated with the incidence of Lyme disease in Connecticut (r =
      0.944). The number of Lyme disease cases has been influenced, in part, by annual
      changes in population densities of I. scapularis and, presumably, a corresponding
      change in the risk of contact with infected ticks. Based upon tick activity and
      spirochetal infection rates, epidemiologically based Lyme disease case reports on
      a regional scale appear to reflect real trends in disease.

PMID- 9574685
TI  - Specificity of rabbit antisera against lipopolysaccharide of Acinetobacter.
AB  - Acinetobacter has been reported to be involved in hospital-acquired infections
      with increasing frequency. However, clinical laboratories still lack simple
      methods that allow the accurate identification of Acinetobacter strains at the
      species level. For this study, proteinase K-digested whole-cell lysates from 44
      clinical and environmental isolates were investigated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and immunoblotting with hyperimmune rabbit
      sera to examine the possibility of developing a serotyping scheme based on the O
      antigen of Acinetobacter lipopolysaccharide (LPS). The antisera, obtained by
      immunization of rabbits with 13 of the heat-killed isolates investigated, were
      characterized by Western blotting and enzyme immunoassay by using proteinase K
      digested whole-cell lysates and phenol-water-extracted LPS as antigens. In both
      assays, the antisera were shown to be highly specific for the homologous antigen.
      In addition, assignment of Acinetobacter LPS to the smooth or the rough phenotype
      was shown not to be reliable when it was based only on the results obtained with
      silver-stained gels. O-antigen reactivity, determined by Western blot analysis,
      was observed with 11 of the 31 isolates, most of which belonged to the species
      Acinetobacter baumannii (DNA group 2) and the unnamed DNA group 3. Interestingly,
      some O antigens were found in a DNA group different from that of the strain used
      for immunization. The results indicate that O serotyping of Acinetobacter strains
      is feasible and thus may provide a simple method for the routine identification
      of these opportunistic pathogens.

PMID- 9574686
TI  - Use of Roche AMPLICOR Mycobacterium tuberculosis PCR in early diagnosis of
      tuberculous meningitis.
AB  - Several nucleic acid-based amplification tests are available for the detection of
      Mycobacterium tuberculosis, but few data are available on their use in the
      diagnosis of tuberculous meningitis (TBM). We performed a prospective study to
      assess the Roche AMPLICOR Mycobacterium tuberculosis PCR test (TB AMPLICOR) for
      use in the diagnosis of TBM and compared it with direct Ziehl-Neelsen staining of
      smears, radiometric culture for M. tuberculosis, and clinical and cerebrospinal
      fluid (CSF) findings. Eighty-three CSF specimens collected from 69 patients with
      suspected meningitis in South Africa were tested by TB AMPLICOR. On the basis of
      clinical and laboratory findings, 40 of these patients were treated for TBM and
      29 patients were not treated for TBM. Ten CSF samples from 10 patients were
      positive by TB AMPLICOR. Seven of these 10 patients were classified as having
      definite TBM, 2 were classified as having probable TBM, and 1 was classified as
      having possible TBM. The sensitivity of TB AMPLICOR for detecting cases of
      definite and probable TBM in patients from whom CSF specimens had been collected
      less than 10 days into antituberculosis treatment was 60.0%. Specimens from all
      29 patients not treated for TBM were negative by the TB AMPLICOR, giving a 100%
      specificity. TB AMPLICOR is therefore more sensitive than the combination of
      Ziehl-Neelsen staining of smears and radiometric culture for M. tuberculosis and
      is a rapid and highly specific diagnostic test for TBM.

PMID- 9574687
TI  - Nonperinatal nosocomial transmission of Candida albicans in a neonatal intensive
      care unit: prospective study.
AB  - Nosocomial Candida albicans infections have become a major cause of morbidity and
      mortality in neonates in neonatal intensive care units (NICUs). To determine the
      possible modes of acquisition of C. albicans in hospitalized neonates, we
      conducted a prospective study at Grady Memorial Hospital, Atlanta, Ga. Clinical
      samples for fungal surveillance cultures were obtained at birth from infants
      (mouth, umbilicus, and groin) and their mothers (mouth and vagina) and were
      obtained from infants weekly until they were discharged. All infants were culture
      negative for C. albicans at birth. Six infants acquired C. albicans during their
      NICU stay. Thirty-four (53%) of 64 mothers were C. albicans positive (positive at
      the mouth, n = 26; positive at the vagina, n = 18; positive at both sites, n =
      10) at the time of the infant's delivery. A total of 49 C. albicans isolates were
      analyzed by restriction endonuclease analysis and restriction fragment length
      polymorphism analysis by using genomic blots hybridized with the CARE-2 probe. Of
      the mothers positive for C. albicans, 3 of 10 were colonized with identical
      strains at two different body sites, whereas 7 of 10 harbored nonidentical
      strains at the two different body sites. Four of six infants who acquired C.
      albicans colonization in the NICU had C. albicans-positive mothers; specimens
      from all mother-infant pairs had different restriction endonuclease and CARE-2
      hybridization profiles. One C. albicans-colonized infant developed candidemia;
      the colonizing and infecting strains had identical banding patterns. Our study
      indicates that nonperinatal nosocomial transmission of C. albicans is the
      predominant mode of acquisition by neonates in NICUs at this hospital; mothers
      may be colonized with multiple strains of C. albicans simultaneously; colonizing
      C. albicans strains can cause invasive disease in neonates; and molecular biology
      based techniques are necessary to determine the epidemiologic relatedness of
      maternal and infant C. albicans isolates and to facilitate determination of the
      mode of transmission.

PMID- 9574688
TI  - Effects of ammonia inhalation and acetic acid pretreatment on colonization
      kinetics of toxigenic Pasteurella multocida within upper respiratory tracts of
      swine.
AB  - Pigs reared in intensive production systems are continuously exposed to ammonia
      released by the microbial degradation of their excrement. Exposure to this gas
      has been shown to increase the severity of the disease progressive atrophic
      rhinitis by facilitating colonization of the pig's upper respiratory tract by
      Pasteurella multocida. The etiological mechanism responsible for this synergy was
      investigated by studying the colonization kinetics of P. multocida enhanced by
      ammonia and comparing them with those evoked by an established disease model.
      Three-week-old Large White piglets were weaned and allocated to five experimental
      groups (groups A to E). Pigs in groups A and B were exposed continuously to
      ammonia at 20 ppm for the first 2 weeks of the study. Pigs in group C were
      pretreated with 0.5 ml of 1% acetic acid per nostril on days -2 and -1 of the
      study. On day 0 all the pigs in groups A, C, and D were inoculated with 1.4 x
      10(8) toxigenic P. multocida organisms given by the intranasal route. The
      kinetics of P. multocida colonization were established by testing samples
      obtained at weekly intervals throughout the study. The study was terminated on
      day 37, and the extent of turbinate atrophy was determined by using a
      morphometric index. The results of the study showed that exposure to aerial
      ammonia for a limited period had a marked effect on the colonization of toxigenic
      P. multocida in the nasal cavities of pigs, which resulted in the almost total
      exclusion of commensal flora. In contrast, ammonia had only a limited effect on
      P. multocida colonization at the tonsil. The exacerbation of P. multocida
      colonization by ammonia was restricted to the period of ammonia exposure, and the
      number of P. multocida organisms colonizing the upper respiratory tract declined
      rapidly upon the cessation of exposure to ammonia. During the exposure period,
      the ammonia levels in mucus recovered from the nasal cavity and tonsil were found
      to be 7- and 3.5-fold higher, respectively, than the levels in samples taken from
      unexposed controls. Acetic acid pretreatment also induced marked colonization of
      the nasal cavity which, in contrast to that induced by ammonia, persisted
      throughout the time course of the study. Furthermore, acetic acid pretreatment
      induced marked but transient colonization of the tonsil. These findings suggest
      that the synergistic effect of ammonia acts through an etiological mechanism
      different from that evoked by acetic acid pretreatment. A strong correlation was
      found between the numbers of P. multocida organisms isolated from the nasal
      cavity and the severity of clinical lesions, as determined by using a
      morphometric index. The data presented in the paper highlight the potential
      importance of ammonia as an exacerbating factor in respiratory disease of
      intensively reared livestock.

PMID- 9574689
TI  - Detection of bovine torovirus in fecal specimens of calves with diarrhea from
      Ontario farms.
AB  - Breda virus (BRV), a member of the genus Torovirus, is an established etiological
      agent of disease in cattle. BRV isolates have been detected in the stools of
      neonatal calves with diarrhea in both Iowa and Ohio and in several areas of
      Europe. However, this virus has been reported only once in Canada. Therefore, a
      study was performed to determine the extent to which bovine torovirus is present
      in calves with diarrhea from farms in southern Ontario. A total of 118 fecal
      samples from symptomatic calves and 43 control specimens from asymptomatic calves
      were examined by electron microscopy (EM) and reverse transcription-PCR (RT-PCR)
      for the presence of torovirus. Torovirus RNA was detected in 43 of the 118
      diarrheic samples (36.4%) by RT-PCR with primers designed in the conserved 3' end
      of the torovirus genome. By EM, torovirus particles were observed in 37 of the
      118 specimens (31.4%). All but one of these samples were also positive by RT-PCR.
      The incidence of torovirus in the asymptomatic control specimens by RT-PCR was
      only 11.6%. To establish the identity of the particles observed in the diarrheic
      specimens, five of the amplicons from samples positive by both RT-PCR and EM were
      cloned and sequenced. Nucleotide sequence analysis revealed that the bovine
      torovirus found in southern Ontario manifests between 96 and 97% sequence
      identity to the BRV type 1 strain found in Iowa. This study shows that bovine
      torovirus is a common virus in the fecal specimens of calves with diarrhea from
      farms in southern Ontario and thus may be an important pathogen of cattle.

PMID- 9574690
TI  - Typing of Helicobacter pylori vacA gene and detection of cagA gene by PCR and
      reverse hybridization.
AB  - The present report describes an analysis of two virulence genes of Helicobacter
      pylori. Parts of the cagA gene, as well as parts from the signal (s) and middle
      (m) regions of the mosaic vacA gene, were amplified with biotin-labelled PCR
      primers and the products were subsequently analyzed by a single-step reverse
      hybridization line probe assay (LiPA). This assay comprises a strip containing
      multiple specific probes for the vacA s region (sla, slb, and s2 alleles), the
      vacA m region (ml and m2 alleles), and the cagA gene. A total of 103 H. pylori
      positive materials, including cultured isolates, gastric biopsy specimens, and
      surgical specimens from patients living in Portugal (n = 55) and The Netherlands
      (n = 48) were tested by the PCR-LiPA. cagA was detected in 84 and 73% of the
      Portuguese and Dutch patients, respectively. vacA typing results, as determined
      by reverse hybridization, were completely concordant with those of sequence
      analysis. Most Portuguese patients (72%) contained type slb, whereas most Dutch
      patients (61%) contained type sla (P < 0.001). The method is also very effective
      at detecting the presence of multiple genotypes in a single biopsy specimen. The
      prevalence of multiple strains in Portuguese patient samples was significantly
      higher (29%) than that in Dutch patient samples (8%) (P = 0.001). There was a
      significant association between the presence of ulcers or gastric carcinoma and
      the presence of vacA type sl (sla or slb; P = 0.008) and cagA (P = 0.003) genes.

PMID- 9574691
TI  - Recombinant mouse-human chimeric antibodies as calibrators in immunoassays that
      measure antibodies to Toxoplasma gondii.
AB  - In the present study, we examined the feasibility of using recombinant antibodies
      containing murine variable regions and human constant regions as calibrators or
      controls in immunoassays. As a model system, we chose the Abbott IMx Toxo
      immunoglobulin M (IgM) and Toxo IgG assays designed to detect antibodies to
      Toxoplasma gondii. Two mouse monoclonal antibodies were selected based on their
      reactivity to the T. gondii antigens P30 and P66. Heavy- and light-chain variable
      region genes were cloned from both hybridomas and transferred into immunoglobulin
      expression vectors containing human kappa and IgG1 or IgM constant regions. The
      constructs were stably transfected into Sp2/0-Ag14 cells. In the IMx Toxo IgG
      assay, immunoreactivity of the anti-P30 chimeric IgG1 antibody paralleled that of
      the positive human plasma-derived assay calibrators. Signal generated with the
      anti-P66 chimeric IgG1 antibody was observed to plateau below the maximal
      reactivity observed for the assay calibrator. Examination of the IgM chimeric
      antibodies in the IMx Toxo IgM assay revealed that both the anti-P30 and anti-P66
      antibodies matched the assay index calibrator manufactured with human Toxo IgM
      positive plasma. When evaluated with patient samples, the correlation between
      results obtained with the chimeric antibody calibrators and the positive human
      plasma calibrators was > or =0.985. These data demonstrate that chimeric mouse
      human antibodies are a viable alternative to high-titer positive human plasma for
      the manufacture of calibrators and controls for diagnostic assays.

PMID- 9574692
TI  - Identification and analysis of a new vacA genotype variant of Helicobacter pylori
      in different patient groups in Germany.
AB  - The vacuolating cytotoxin of Helicobacter pylori (VacA) is known to cause cell
      damage to mammalian cells and is suspected to give rise to gastric epithelial
      lesions that might lead to peptic ulcer disease. As shown recently, the gene
      encoding VacA exhibits genetic variation, with three different families of signal
      sequences (s1a, s1b, and s2) and two families of midregion sequences (m1 and m2).
      In order to investigate the relationship between the presence of specific vacA
      genotypes and peptic ulceration, the vacA genotypes of 158 clinical isolates of
      H. pylori were determined. The study group consisted of 106 patients with
      duodenal ulceration; 52 patients with nonulcer dyspepsia (NUD) were used as
      controls. H. pylori of genotype s1 was isolated from 96% of the patients with
      ulcerations, whereas genotype s2 was only present in 4%, indicating a strong
      correlation between the vacA genotype and peptic ulceration (P < 0.001). In
      contrast, 31% of the patients from the NUD control group were infected with
      strains of vacA genotype s2. Particular midregion genotypes (m1 and m2) were not
      associated with clinical manifestations. The midregions from 18% of the isolates
      could not be classified by the proposed scheme. DNA sequencing revealed high
      homology between the untypeable midregions and that of genotype m1, with multiple
      base pair exchanges, some affecting the primer annealing site. Compared to those
      of m1 and m2 alleles, the divergent midregions from untypeable strains showed
      clustering, indicating the presence of a further subfamily of sequences in the
      midregion of vacA in German isolates, for which we propose the term "m1a." A new
      specific primer that we designed for typing m1a isolates might be useful in other
      studies.

PMID- 9574693
TI  - Gemella bergeriae sp. nov., isolated from human clinical specimens.
AB  - Six strains of a hitherto-undescribed gram-positive, catalase-negative,
      facultatively anaerobic coccus from human sources were characterized by
      phenotypic and molecular taxonomic methods. Comparative 16S rRNA gene sequencing
      studies demonstrated that the unknown strains are genealogically homogeneous and
      constitute a new subline within the genus Gemella. The unknown bacterium was
      readily distinguished from Gemella haemolysans, the type species of the genus
      Gemella, and from Gemella morbillorum by biochemical tests and electrophoretic
      analysis of whole-cell proteins. On the basis of phylogenetic and phenotypic
      evidence, it is proposed that the unknown bacterium from clinical specimens be
      classified as Gemella bergeriae sp. nov. The type strain of G. bergeriae is CCUG
      37817 (= strain 617-93).

PMID- 9574694
TI  - Molecular epidemiological study of Aspergillus fumigatus in a bone marrow
      transplantation unit by PCR amplification of ribosomal intergenic spacer
      sequences.
AB  - We have developed a PCR-based method for the subspecific discrimination of
      Aspergillus fumigatus types by using two primers designed to amplify the
      intergenic spacer regions between ribosomal DNA transcription units. The method
      permitted the reproducible discrimination of 11 distinct DNA types among a total
      of 119 isolates of A. fumigatus collected from patients and from the environment
      of a bone marrow transplantation (BMT) unit over a three-year period. Ten DNA
      types of A. fumigatus were isolated from patients in the BMT unit; eight of these
      types were also found in the hospital environment, and six of these were present
      in the unit itself. Thirteen BMT patients developed infection with one of three
      DNA types some months after these had first been found in the environment of the
      unit. In other instances, the same DNA types of A. fumigatus were isolated from
      BMT patients that were later recovered from the environment of the unit. Several
      DNA types of A. fumigatus were found in the hospital environment over an 18-month
      period. Molecular typing of multiple isolates of A. fumigatus, obtained from
      postmortem tissue samples, showed that one patient was infected with a single DNA
      type, but two others had up to three different DNA types. Our findings suggest
      that A. fumigatus infection in BMT recipients may be nosocomial in origin and
      underline the need for careful environmental monitoring of units in which high
      risk patients are housed.

PMID- 9574695
TI  - Use of ligase chain reaction with urine versus cervical culture for detection of
      Chlamydia trachomatis in an asymptomatic military population of pregnant and
      nonpregnant females attending Papanicolaou smear clinics.
AB  - Ligase chain reaction (LCR) (Abbott Laboratories, Abbott Park, Ill.) with first
      catch urine specimens was used to detect Chlamydia trachomatis infections in 465
      asymptomatic military women attending clinics for routine Papanicolaou smear
      tests. Results were compared to results of cervical culture to determine the
      sensitivity of the urine LCR and the possible presence of inhibitors of
      amplification in pregnant and nonpregnant women. Discrepant results for LCR and
      culture were resolved by direct fluorescent antibody staining of culture
      sediments, two different PCR assays, and LCR for the outer membrane protein 1
      gene. The prevalence of Chlamydia in specimens by urine LCR was 7.3% compared to
      5% by culture. For 434 women with matching specimens, there were 11 more
      specimens positive by LCR than were positive by culture, of which all but one
      were determined to be true positives. There were four culture-positive, LCR
      negative specimens, all from nonpregnant women. The sensitivity, specificity, and
      positive and negative predictive values of urine LCR after discrepant results
      were resolved were 88.6, 99.7, 96.9, and 99.0%, respectively. The sensitivity of
      culture was 71.4%. From the 148 pregnant women (prevalence by LCR, 6.8%), there
      were no patients who were cervical culture positive and urine LCR negative to
      indicate the presence in pregnant women of inhibitors of LCR. Additionally, a
      subset of 55 of the LCR-negative frozen urine specimens from pregnant women that
      had been previously processed in LCR buffer were inoculated with 5 cell culture
      inclusion forming units of C. trachomatis each and retested by LCR; all tested
      positive, indicating the absence of inhibitors of LCR in urine from these
      pregnant women. The use of LCR testing of urine specimens from asymptomatic
      women, whether pregnant or not, offers a sensitive and easy method to detect C.
      trachomatis infection in women.

PMID- 9574696
TI  - Phylogenetic placement of rickettsiae from the ticks Amblyomma americanum and
      Ixodes scapularis.
AB  - A rickettsial isolate (isolate MOAa) belonging to the spotted fever group (SFG)
      was obtained from the lone star tick Amblyomma americanum. We used PCR to
      characterize the genes for the rickettsial outer membrane proteins rOmpA and
      rOmpB. We sequenced the PCR products (domains I of both the rompA gene and the
      rompB gene) of MOAa and WB-8-2, another rickettsial isolate from A. americanum.
      To place MOAa and WB-8-2 and two other nonpathogenic isolates (Rickettsia
      rickettsii Hip2 and Rickettsia montana M5/6) with respect to their putative
      sister species, we included them in a phylogenetic analysis of 9 Rickettsia
      species and 10 Rickettsia strains. Our phylogenetic results implied three
      evolutionary lineages of SFG rickettsiae and that WB-8-2 and MOAa were most
      closely related to R. montana. New World isolates were not the most closely
      related to each other (they did not form a clade). Rather, our results supported
      four independent origins (introductions) of rickettsiae into North America from
      different Old World regions. The results of our phylogenetic analysis did not
      support the hypothesis of a stable coevolution of rickettsiae and their tick
      hosts. Finally, we examined the rompA gene of a nonpathogenic rickettsial
      symbiont isolated from the tick Ixodes scapularis. In a phylogenetic analysis,
      the symbiont was placed as the sister to R. montana and its isolates. The
      relationship of this symbiont to R. montana raised questions as to the potential
      origin of pathogenic SFG rickettsiae from nonpathogenic tick symbionts, or vice
      versa.

PMID- 9574697
TI  - Computerized analysis of restriction fragment length polymorphism patterns:
      comparative evaluation of two commercial software packages.
AB  - Two computerized restriction fragment length polymorphism pattern analysis
      systems, the BioImage system and the GelCompar system (Molecular Analyst
      Fingerprinting Plus in the United States), were compared. The two systems use
      different approaches to compare patterns from different gels. In GelCompar, a
      standard reference pattern in one gel is used to normalize subsequent gels
      containing lanes with the same reference pattern. In BioImage, the molecular
      sizes of the fragments are calculated from size standards present in each gel.
      The molecular size estimates obtained with the two systems for 12 restriction
      fragments of phage lambda were between 97 and 101% of their actual sizes, with a
      standard deviation of less than 1% of the average estimated size for most
      fragments. At the window sizes used for analysis, the GelCompar system performed
      somewhat better than BioImage in identifying visually identical patterns
      generated by electrophoretic separation of HhaI-restricted DNA of Listeria
      monocytogenes. Both systems require the user to make critical decisions in the
      analysis. It is very important to visually verify that the systems are finding
      all bands in each lane and that no artifacts are being detected; both systems
      allow manual editing. It is also important to verify results obtained in the
      pattern matching or clustering portions of the analysis.

PMID- 9574698
TI  - Rapid diagnosis of extrapulmonary tuberculosis by ligase chain reaction
      amplification.
AB  - A rapid amplification-based test for the diagnosis of extrapulmonary
      tuberculosis, the LCx Mycobacterium tuberculosis Assay from Abbott Laboratories,
      was evaluated. Results from the LCx M. tuberculosis Assay were compared with
      those from culture and the final clinical diagnosis for each patient. A total of
      526 nonrespiratory specimens from 492 patients were tested. The specimens
      included urine; feces; lymph node exudates; pleural, cerebrospinal, articular,
      and ascitic fluids; tissue biopsies; gastric aspirates; purulent exudates; blood;
      and bone marrow aspirates. After combination of the culture results and the
      patient's clinical data, a total of 135 specimens were collected from 122
      patients with a diagnosis of extrapulmonary tuberculosis. The sensitivity,
      specificity, and positive and negative predictive values for the LCx M.
      tuberculosis Assay were 77.7, 98.7, 95.2, and 93.1%, respectively; these values
      rose in resolved cases of TB to 78.5, 100, 100, and 93.1%, respectively. For 37
      (27.4%) specimens from patients smear positive for the disease and 98 (72.6%)
      specimens from patients smear negative for the disease, the sensitivities of the
      LCx M. tuberculosis Assay were 100 and 71.1%, respectively. Statistically
      significant differences (P < 0.01) in sensitivities were found between culture
      and the LCx M. tuberculosis Assay. These differences were even greater among
      smear-negative specimens. The results demonstrate that the LCx M. tuberculosis
      Assay will provide rapid and valuable information for the diagnosis of
      extrapulmonary tuberculosis.

PMID- 9574699
TI  - Comparative evaluation of National Committee for Clinical Laboratory Standards
      broth macrodilution and agar dilution screening methods for testing fluconazole
      susceptibility of Cryptococcus neoformans.
AB  - A simple screening method for fluconazole susceptibility of Cryptococcus
      neoformans using 2% dextrose Sabouraud dextrose agar (SabDex) with fluconazole
      was compared to the National Committee for Clinical Laboratory Standards (NCCLS)
      broth macrodilution method. By this method, fluconazole-susceptible C. neoformans
      isolates are significantly smaller on medium with fluconazole than on fluconazole
      free medium. Isolates with decreased susceptibility have normal-size colonies on
      medium containing fluconazole. The 48-h NCCLS broth macrodilution MICs (NCCLS
      MICs) for isolates with normal-size colonies on 8- or 16-microg/ml fluconazole
      plates were predicted to be > or =8 or > or =16 microg/ml, respectively. On
      medium with 16 microg of fluconazole per ml, all strains (84 of 84) for which the
      NCCLS MICs were <16 microg/ml were correctly predicted, as were all isolates (7
      of 7) for which the MICs were > or =16 microg/ml. Agar dilution appears to be an
      effective screening method for fluconazole resistance in C. neoformans.

PMID- 9574700
TI  - Evaluation of Murex CMV DNA hybrid capture assay for detection and quantitation
      of cytomegalovirus infection in patients following allogeneic stem cell
      transplantation.
AB  - Murex hybrid capture DNA assay (HCS) is a solution hybridization antibody capture
      assay for detection and quantitation of cytomegalovirus (CMV) DNA in leukocytes.
      To determine whether CMV HCS is sensitive enough to initiate and monitor
      antiviral therapy after allogeneic stem cell transplantation (SCT), 51
      consecutive SCT recipients were prospectively screened for the appearance of CMV
      infection by HCS, PCR, and culture assays from blood samples. Preemptive
      antiviral therapy was initiated after the second positive PCR result in all
      patients, as previously reported, and HCS was not considered for clinical
      decision making. A total of 417 samples were analyzed. Of these, 21 samples were
      found to be positive by PCR and HCS, 88 samples were PCR positive but HCS
      negative, and 308 were negative by both assays. Concordance of results between
      PCR and HCS and between HCS and blood culture was observed in 78.9 and 95.9% of
      the samples assayed, respectively. PCR was found to be more sensitive than HCS,
      and HCS was more sensitive than the blood culture assay (P < 0.0001). Four
      patients with symptomatic CMV infection were PCR positive prior to the onset of
      CMV-related symptoms, whereas HCS detected CMV DNA in three patients prior to and
      one at onset of CMV disease. The numbers of genomes per milliliter of blood were
      higher in patients with symptomatic CMV infection than in those with asymptomatic
      CMV infection (P = 0.06). None of the HCS-negative patients developed CMV
      disease. Thus, all patients with CMV disease were correctly identified by HCS;
      however, the lower sensitivity limit of the HCS assay may still be insufficient
      to allow diagnosis of CMV infection early enough to prevent CMV disease in
      patients following allogeneic SCT.

PMID- 9574701
TI  - Comparison of nine commercially available enzyme-linked immunosorbent assays for
      detection of Giardia lamblia in fecal specimens.
AB  - Overall performance, including ease of use, total hands-on time, incubation and
      processing times, sensitivity, and specificity, of each of nine enzyme-linked
      immunosorbent assays (ELISAs) were compared by using 222 individual fecal samples
      submitted for the detection of Giardia lamblia. The assays evaluated were
      manufactured by Alexon, Inc., Cambridge Biotech Corp., Meridian, Inc., and Trend
      Scientific, Inc. All assays used polyclonal antibodies except the "new and
      improved" Microplate (direct and diluted methods) by Alexon, which is a
      monoclonal antibody assay. Seventy specimens were positive for G. lamblia by
      ELISA, ova and parasite test, and/or direct fluorescent-antibody assay. One
      hundred fifty two were negative by all three methods. Sensitivities and
      specificities ranged from 88.6 to 100% and 99.3 to 100%, respectively. The total
      hands-on time needed to run one specimen ranged from 1 min to 2 min 17 s per
      specimen. All except one commercially available ELISA were found to be rapid,
      sensitive, and specific for the detection of G. lamblia in fecal specimens.

PMID- 9574702
TI  - Diagnostic value of monitoring human cytomegalovirus late pp67 mRNA expression in
      renal-allograft recipients by nucleic acid sequence-based amplification.
AB  - The diagnostic value of monitoring human cytomegalovirus (HCMV) late pp67 mRNA
      expression by nucleic acid sequence-based amplification (NASBA) after renal
      allograft transplantation was evaluated. RNAs were isolated from 489 whole-blood
      specimens of 42 patients for the specific amplification of the late pp67 (UL65)
      mRNA. NASBA results were compared to results from the pp65 antigenemia assay,
      virus isolation by cell culture, and serology. The sensitivity value for NASBA
      proved to be higher than that for the antigenemia assay (50 versus 35%) for the
      detection of HCMV infection, while the sensitivity values of cell culture and
      NASBA were comparable (54 and 50%, respectively). NASBA detected the onset of
      HCMV infection simultaneously with cell culture and the antigenemia assay. Both
      the antigenemia assay and NASBA are very specific (100%) and highly predictive
      (100%) for the onset of HCMV infection. Antiviral therapy with ganciclovir
      resulted in negative results for cell culture, the antigenemia assay, and NASBA.
      In conclusion, monitoring HCMV pp67 mRNA expression by NASBA is a highly specific
      method for the detection of HCMV infection in renal-allograft recipients and is
      more sensitive than the antigenemia assay. Furthermore, NASBA can be used to
      monitor the progression of HCMV infections and the effect of antiviral therapy on
      viral activity.

PMID- 9574703
TI  - Persistence of a multidrug-resistant Pseudomonas aeruginosa clone in an intensive
      care burn unit.
AB  - Long-term colonization of various body sites with a multidrug-resistant
      Pseudomonas aeruginosa clone (resistant to piperacillin, cefoperazone,
      ceftazidime, aztreonam, imipenem, cefepime, cefpirome, ofloxacin, ciprofloxacin,
      minocycline, and aminoglycosides) with subsequent severe infections in burn
      patients has not been reported previously. Thirty-nine isolates of multidrug
      resistant P. aeruginosa (resistant to ceftazidime and at least three of the
      agents listed above) recovered from various clinical samples from three patients
      in an intensive care burn unit from April 1997 to May 1997 and seven preserved
      isolates recovered from six patients in other medical wards at National Taiwan
      University Hospital from April 1996 to May 1997 were studied for their
      epidemiological relatedness. The epidemic could be attributed to a multidrug
      resistant P. aeruginosa clone belonging to serogroup O:F (serogroup O:4) by means
      of antimicrobial susceptibility testing, O serogrouping, and analysis of the
      randomly amplified polymorphic DNA patterns generated by arbitrarily primed PCR
      of the isolates. The epidemic strain persisted in the three patients for weeks to
      months; in the meantime, these patients had received multiple antimicrobial
      agents for the management of intervening episodes of invasive infections
      (bacteremia, ventilator-associated pneumonia, and/or catheter-related sepsis)
      caused by this strain, as well as concomitant infections due to other organisms.
      The strain had been isolated only once previously, from a burn patient who was on
      the unit in December 1996. The present report, describing a small outbreak due to
      P. aeruginosa, documents the fact that a single clone of multidrug-resistant P.
      aeruginosa can cause long-term persistence in different body sites of burn
      patients and that the colonization can subsequently result in various severe
      infections.

PMID- 9574704
TI  - Reverse transcription-PCR detection of Mycobacterium leprae in clinical
      specimens.
AB  - A reverse transcription (RT)-PCR assay targeting the 16S rRNA of Mycobacterium
      leprae was developed to detect the organism in clinical specimens. A 171-bp
      fragment was amplified when M. leprae RNA was used as a template but not when a
      panel of RNAs from 28 potentially cross-reacting mycobacterial species, seven
      genera related to Mycobacterium, and three organisms normally found among skin or
      nose flora were tested. As few as 10 organisms isolated from infected tissue
      could be detected, confirming the sensitivity of the assay. When the test was
      applied to clinical specimens, M. leprae was detected in 82% of skin biopsy
      specimens obtained from untreated leprosy patients, while skin biopsy specimens
      from healthy volunteers and patients with other dermatological disorders were
      negative. The sensitivity of the RT-PCR was higher than that of slit skin smear
      staining for acid-fast bacilli or acid-fast staining of fixed biopsy specimens
      since 53% of acid-fast bacillus-negative biopsy specimens were RT-PCR positive.
      Because 16S rRNA is rapidly degraded upon cell death, the assay may detect only
      viable organisms and may prove to be useful in assessing the efficacy of
      chemotherapy.

PMID- 9574705
TI  - Nosocomial outbreak of Klebsiella pneumoniae producing SHV-5 extended-spectrum
      beta-lactamase, originating from a contaminated ultrasonography coupling gel.
AB  - Klebsiella pneumoniae resistant to ceftazidime was isolated from six adult women
      and two neonates hospitalized between July and November 1993 in the Department of
      Obstetrics and Gynecology of Boucicaut Hospital (Paris, France). The
      epidemiological investigation revealed a notably short delay (less than 48 h)
      between admission and contamination of the six adults and peripartum transmission
      to the neonates. The only environmental source of ceftazidime-resistant K.
      pneumoniae was the ultrasonography coupling gel used in the emergency room.
      Phenotypic (biotyping and antibiotyping) and genotypic (plasmid profile and
      pulsed-field gel electrophoresis) analysis of all the clinical isolates indicated
      the spread of a single strain. It produced SHV-5 and TEM-1 beta-lactamases, as
      demonstrated by isoelectric focusing and gene sequencing. The risk of cross
      contamination in ultrasonography procedures is usually low and had not been
      associated so far with bacteria producing an extended-spectrum beta-lactamase
      (ESBL). Furthermore, this is the first time an epidemic of an SHV-5 ESBL
      producing member of the family Enterobacteriaceae has been reported from a French
      hospital.

PMID- 9574706
TI  - Effects of following National Committee for Clinical Laboratory Standards and
      Deutsche Industrie Norm-Medizinische Mikrobiologie guidelines, country of isolate
      origin, and site of infection on susceptibility of Escherichia coli to
      amoxicillin-clavulanate (Augmentin).
AB  - Amoxicillin-clavulanate (Augmentin), as a combination of two active agents, poses
      extra challenges over single agents in establishing clinically relevant
      breakpoints for in vitro susceptibility tests. Hence, reported differences in
      amoxicillin-clavulanate percent susceptibilities among Escherichia coli isolates
      may reflect localized resistance problems and/or methodological differences in
      susceptibility testing and breakpoint criteria. The objectives of the present
      study were to determine the effects of (i) methodology, e.g., those of the
      National Committee for Clinical Laboratory Standards (NCCLS) and the Deutsche
      Industrie Norm-Medizinische Mikrobiologie (DIN), (ii) country of origin (Spain,
      France, and Germany), and (iii) site of infection (urinary tract, intra-abdominal
      sepsis, or other site[s]) upon the incidence of susceptibility to amoxicillin
      clavulanate in 185 clinical isolates of E. coli. Cefuroxime and cefotaxime were
      included for comparison. The use of NCCLS methodology resulted in different
      distribution of amoxicillin-clavulanate MICs than that obtained with the DIN
      methodology, a difference highlighted by the 10% more strains found to be within
      the 8- to 32-microg/ml MIC range. This difference reflects the differing amounts
      of clavulanic acid present. NCCLS and DIN methodologies also produce different
      MIC distributions for cefotaxime but not for cefuroxime. Implementation of NCCLS
      and DIN breakpoints produced markedly different incidences of strains that were
      found to be susceptible, intermediate or resistant to amoxicillin-clavulanate. A
      total of 86.5% strains were found to be susceptible to amoxicillin-clavulanate by
      the NCCLS methodology, whereas only 43.8% were found to be susceptible by the DIN
      methodology. Similarly, 4.3% of the strains were found to be resistant by NCCLS
      guidelines compared to 21.1% by the DIN guidelines. The use of DIN breakpoints
      resulted in a fivefold-higher incidence of strains categorized as resistant to
      cefuroxime. There were no marked differences due to country of origin upon the
      MIC distributions for amoxicillin-clavulanate, cefuroxime, or cefotaxime, as
      determined with the NCCLS guidelines. Isolates from urinary tract and intra
      abdominal infections were generally more resistant to amoxicillin-clavulanate
      than were isolates from other sites of infection.

PMID- 9574707
TI  - Presence of multiple "Helicobacter heilmannii" strains in an individual suffering
      from ulcers and in his two cats.
AB  - Circumstantial evidence suggests that "Helicobacter heilmannii" infection is an
      example of zoonosis. The presence of "H. heilmannii" strains in a human subject
      with acute gastric erosions, in his two cats, and in two unrelated cats was
      analyzed, and the genetic relatedness of the human and feline strains was
      assessed. A 580-bp, PCR-amplified sequence of "H. heilmannii" urease B gene
      (ureB) obtained from biopsies from the human subject and his two cats was
      restricted with AluI and cloned for sequencing. Analysis of the restriction
      fragment length polymorphism of the ureB-amplified product suggested the presence
      of different individual "H. heilmannii" strains in the cats and of three distinct
      strains in the human subject. One of the "H. heilmannii" ureB sequences amplified
      from the human subject's biopsies was identical to that derived from one of his
      cats. The degree of similarity between the other "H. heilmannii" human and feline
      nucleotide sequences was higher than 97%. Most of the base substitutions were
      conservative. We conclude that human and animal "H. heilmannii" strains are
      closely related and that humans can be infected by more than one "H. heilmannii"
      strain, as has been observed for Helicobacter pylori.

PMID- 9574708
TI  - Genotypic and phenotypic analysis of Mycoplasma fermentans strains isolated from
      different host tissues.
AB  - A correlation was found between the expression of a specific Mycoplasma
      fermentans surface antigen (Pra, proteinase-resistant antigen) and the site of
      isolation of the organism from the infected host. Strains which expressed Pra
      were most frequently associated with cells of bone marrow origin, and strains
      which lacked expression of Pra were most commonly isolated from the respiratory
      tract, genital tract, and arthritic joints, i.e., epithelial cell surfaces. Pra
      was previously shown to be resistant to degradation by proteinases and was
      hypothesized to play a protective role at the organism surface and perhaps to
      influence which host tissue site was colonized by the organism. The methods used
      for this phenotyping scheme required isolation and growth of the mycoplasma in
      quantities sufficient for immunoblot analysis using monoclonal antibodies. We
      wanted to determine a more rapid and less cumbersome technique to supplement this
      method for determining the Pra phenotype directly in clinical specimens. Here we
      describe PCR studies to investigate the movement of a previously identified M.
      fermentans insertion sequence (IS)-like element. These data showed a correlation
      between a specific IS genotype and the Pra+ phenotype. Production of a 160-bp
      product using a single set of IS-based primers was associated with expression of
      Pra. The genomic IS location resulting in the 160-bp product was determined by
      using Southern blot analysis and was found to be a stable insertion site
      characteristic of genotype I strains. Additional analyses of sequences within and
      flanking the IS insertion sites revealed another pair of PCR primer sites which
      resulted in the consistent production of a 450-bp amplicon. The stability of this
      site was dependent on the absence of the IS-like element between the primer
      sites. The production of this 450-bp amplicon correlated with the Pra mutant
      phenotype and was characteristic of genotype II strains. The data showed that the
      sequence within the IS may be unstable and that reliable genotyping sequences are
      more easily found in the stable genomic sites which flank the IS element.

PMID- 9574709
TI  - Multicenter comparison of ESP Culture System II with BACTEC 460TB and with
      Lowenstein-Jensen medium for recovery of mycobacteria from different clinical
      specimens, including blood.
AB  - The recently developed ESP Culture System II (AccuMed, Chicago, Ill.) was
      compared with radiometric BACTEC 460TB (Becton Dickinson, Towson, Md.) and with
      Lowenstein-Jensen medium for recovery of mycobacteria from over 2,500 clinical
      specimens both of respiratory and nonrespiratory origin, including blood. The
      majority of the 219 mycobacterial isolates (129) belonged to the Mycobacterium
      tuberculosis complex, followed by 37 isolates of the Mycobacterium avium complex
      (MAC) and 53 isolates of eight other mycobacterial species. Rates of recovery
      obtained with BACTEC, ESP, and Lowenstein-Jensen medium were 89, 79, and 64%,
      respectively, with such differences being statistically significant. Different
      media and systems appeared to behave differently when the more frequently
      detected organisms were considered: M. tuberculosis complex isolates grew better
      with BACTEC, and MAC isolates grew better with ESP. An analysis of the
      combinations of Lowenstein-Jensen medium with BACTEC and with ESP did not reveal
      significant differences in recovery rates. With regard to the times needed for
      the detection of positive cultures, they were significantly longer on Lowenstein
      Jensen medium (average, 28 days) than with the remaining two systems, between
      which there was no difference (average, 18 days). We conclude, therefore, that
      the ESP system, when used in combination with a solid medium, performs as well as
      the thoroughly validated radiometric BACTEC system and offers the advantages of
      full automation and absence of radioisotopes.

PMID- 9574710
TI  - Comparison of methods of identifying Helicobacter hepaticus in B6C3F1 mice used
      in a carcinogenesis bioassay.
AB  - In a long-term rodent bioassay evaluating the carcinogenicity of triethanolamine,
      there was equivocal evidence of carcinogenic activity in male B6C3F1 mice, based
      on a marginal increase in the number of hepatocellular adenomas and
      hepatoblastomas. Interpretation was complicated by the presence of Helicobacter
      hepaticus in selected silver-stained liver sections which also had histological
      evidence of karyomegaly and oval cell hyperplasia. An increase in numbers of
      liver tumors, as evidence of carcinogenic activity, was also noted in female
      mice. However, H. hepaticus was not considered a complicating factor, because the
      livers of the female mice did not have histological features compatible with H.
      hepaticus infection. A retrospective analysis of 51 liver tissue samples from the
      original carcinogenicity study was conducted to determine the incidence of H.
      hepaticus infection and to evaluate different diagnostic approaches for assessing
      the presence of H. hepaticus in livers lacking characteristic lesions. In an
      initial evaluation of seven mice with liver tumors, argyrophilic bacteria
      resembling H. hepaticus were observed in liver sections, associated with
      characteristic liver lesions of hepatocytic karyomegaly and oval cell
      hyperplasia. Frozen liver tissue was available from four of these mice; all were
      confirmed to be infected with H. hepaticus by culture and PCR. In a larger
      subsequent analysis using frozen liver tissues from 44 mice without
      characteristic hepatic lesions, H. hepaticus-specific DNA was amplified from the
      livers of 21 of 44 of the mice (47%), compared to 14 of 44 of the mice (32%)
      having H. hepaticus cultured from their frozen liver tumors. The results of H.
      hepaticus culture and H. hepaticus-specific PCR concurred (i.e., both positive
      and negative results) in 84% of the cases. Microscopic detection of
      immunofluorescence-labeled or silver-stained bacteria in liver sections was
      relatively insensitive compared to either culture or PCR detection. This study
      confirms the widespread prevalence of H. hepaticus in mice, its potential to
      confound experimental results, and the need to include diagnostic testing for H.
      hepaticus in a murine health monitoring program.

PMID- 9574711
TI  - Simultaneous detection and identification of human parainfluenza viruses 1, 2,
      and 3 from clinical samples by multiplex PCR.
AB  - Reverse transcription (RT)-PCR assays have been widely described for use in the
      diagnosis of human parainfluenza viruses (HPIVs) and other respiratory virus
      pathogens. However, these assays are mostly monospecific, requiring separate
      amplifications for each HPIV type. In the present work, we describe multiplex RT
      PCR assays that detect and differentiate HPIV serotypes 1, 2, and 3 in a combined
      reaction. Specifically, a mixture of three pairs of primers to conserved regions
      of the hemagglutinin-neuraminidase gene of each HPIV serotype was used for
      primary amplification, yielding amplicons with similar sizes. For typing, a
      second amplification was performed with a mixture of nested primers, yielding
      amplicons with sizes easily differentiated by agarose gel electrophoresis. A
      modified single-amplification RT-PCR assay with fluorescence-labeled nested
      primers, followed by analysis of the labeled products on an automated sequencing
      gel, was also evaluated. Fifteen temporally and geographically diverse HPIV
      isolates from the Centers for Disease Control and Prevention archives and 26 of
      30 (87%) previously positive nasopharyngeal specimens (8 of 10 positive for HPIV
      serotype 1 [HPIV1], 9 of 10 positive for HPIV2, and 9 of 10 positive for HPIV3)
      were positive and were correctly typed by both assays. Negative results were
      obtained with naso- or oropharyngeal specimens and/or culture isolates of 33
      unrelated respiratory tract pathogens, including HPIV4, enterovirus, rhinovirus,
      respiratory syncytial virus, adenovirus, influenza virus, and Streptococcus
      pneumoniae. Our multiplex RT-PCR assays provide sensitive, specific, and
      simplified tools for the rapid diagnosis of HPIV infections.

PMID- 9574712
TI  - Simplified quantitative assay system for measuring activities of drugs against
      intracellular Legionella pneumophila.
AB  - We developed a new simple assay for the quantitation of the activities of drugs
      against intracellular Legionella pneumophila. The cells of a murine macrophage
      like cell line (J774.1 cells) allowed the intracellular growth and replication of
      the bacteria, which ultimately resulted in cell death. The infected J774.1 cell
      monolayers in 96-well microplates were first treated with antibiotics and were
      further cultured for 72 h. The number of viable J774.1 cells in each well was
      quantified by a colorimetric assay with 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) and an enzyme-linked immunosorbent assay
      reader. The number of growing bacteria in each well was also determined by
      counting the numbers of CFU on buffered charcoal yeast extract-alpha agar plates.
      Viable J774.1 cell counts, determined by the colorimetric assay, were inversely
      proportional to the number of intracellular replicating bacteria. The minimum
      extracellular concentrations (MIECs) of 24 antibiotics causing inhibition of
      intracellular growth of L. pneumophila were determined by the colorimetric assay
      system. The MIECs of beta-lactams and aminoglycosides were markedly higher than
      the MICs in buffered yeast extract-alpha broth. The MIECs of macrolides,
      fluoroquinolones, rifampin, and minocycline were similar to the respective MICs.
      According to their intracellular activities, clarithromycin and sparfloxacin were
      the most potent among the macrolides or fluoroquinolones tested in this study.
      Our results indicated that the MTT assay system allows comparative and
      quantitative evaluations of the intracellular activities of antibiotics and
      efficient processing of a large number of samples.

PMID- 9574713
TI  - Molecular epidemiology of oral treponemes associated with periodontal disease.
AB  - Periodontitis, a disease responsible for tooth loss worldwide, is characterized
      by chronic inflammation of the periodontium, eventually leading to destruction of
      periodontal ligaments and supporting alveolar bone. Spirochetes, identified by
      dark-field microscopy as being the most predominant bacteria in advanced lesions,
      are thought to play a causative role. Various spirochetal morphotypes were
      observed, but most of these morphotypes are as yet uncultivable. To assess the
      role of these organisms we designed oligonucleotide probes for the identification
      of both cultivable and so far uncultivable spirochetes in periodontitis patients.
      Subgingival plaque specimens taken from diseased sites (n = 200) and healthy
      control sites (n = 44) from 53 patients with rapidly progressive periodontitis
      (RPP) were submitted to direct in situ hybridization or dot blot hybridization
      after prior amplification with eubacterial primers. Spirochetes were found in all
      patients, but their distributions varied considerably. Parallel use of
      oligonucleotide probes specific for cultivable or so far uncultivable treponemes
      suggested the presence of novel yet unknown organisms at a high frequency. These
      uncultivable treponemes were visualized by fluorescence in situ hybridization,
      and their morphologies, sizes, and numbers could be estimated. All RPP patients
      included in this study harbored oral treponemes that represent either novel
      species, e.g., Treponema maltophilum, or uncultivable phylotypes. Therefore, it
      is necessary to include these organisms in etiologic considerations and to
      strengthen efforts to cultivate these as yet uncultivable treponemes.

PMID- 9574714
TI  - Identification of acinetobacters on blood agar in presence of D-glucose by unique
      browning effect.
AB  - A positive phenotypic characteristic of glucose-oxidizing acinetobacters was
      demonstrated with blood agar containing D-glucose. Glucose-oxidizing
      Acinetobacter baumannii, Acinetobacter genospecies 3, Acinetobacter lwoffii, and
      Acinetobacter genospecies 13 sensu Tjernberg and Ursing caused a unique brown
      discoloration of media supplemented with 5% blood (of horse, sheep, or human
      origin) and an aldose sugar (0.22 M D-glucose, D-galactose, D-mannose, D-xylose,
      or lactose). The browning effect was not observed when a ketose sugar (D-fructose
      or sucrose) was substituted for the aldose sugar or under high osmolarity in the
      presence of mannitol, glycerol, or sodium chloride. Other gram-negative
      nonfermenters (non-glucose-oxidizing acinetobacters, Pseudomonas aeruginosa,
      other Pseudomonas spp., Stenotrophomonas maltophilia, Flavobacterium spp., and
      Moraxella spp.) did not cause similar discoloration. This novel browning effect
      may serve as an alternative trait for identifying glucose-oxidizing
      acinetobacters.

PMID- 9574715
TI  - Isolation of a nonpathogenic strain of Citrobacter sedlakii which expresses
      Escherichia coli O157 antigen.
AB  - A nonpathogenic strain of Citrobacter sedlakii which expresses the Escherichia
      coli O157 antigen is described. The discovery of this strain emphasizes the
      necessity of additional biochemical and/or toxigenicity testing when isolates
      react with E. coli O157 latex reagents.

PMID- 9574716
TI  - Nonrandom association of IS6110 and Mycobacterium tuberculosis: implications for
      molecular epidemiological studies.
AB  - IS6110 restriction fragment length polymorphism typing is now established as the
      primary typing method for Mycobacterium tuberculosis. It has been assumed that
      the position of bands is random. Thus, the discrimination of the technique
      increases in proportion to the copy number. Two collections of M. tuberculosis
      were investigated to test this hypothesis. We identified 33 positions in isolates
      from a Tanzanian collection and 25 positions in isolates from a London, United
      Kingdom, collection where bands were significantly more likely to be present than
      would be expected by chance. These data suggest that band position is not random,
      and this possibility may have an impact on the interpretation of molecular
      epidemiological studies of M. tuberculosis.

PMID- 9574717
TI  - Novel enzyme-linked immunoassay to determine nanogram levels of pneumocandins in
      human plasma.
AB  - A binding enzyme-linked immunosorbent assay (ELISA) has been developed for
      measuring nanogram concentrations of semisynthetic pneumocandin antifungal agents
      in human plasma. Semisynthetic pneumocandin L-733,560 was conjugated to
      succinylated hemocyanin by water-soluble carbodiimide and was used as an
      immunogen to produce polyclonal antibodies in rabbits. Pneumocandins were used to
      directly coat the wells of a microtiter plate, and quantitation was achieved by
      using rabbit polyclonal antibodies to pneumocandin L-733,560 and goat anti-rabbit
      immunoglobulin G conjugated to either alkaline phosphatase or horseradish
      peroxidase. Maximum binding of L-733,560 and most related analogs to the wells of
      the microtiter plate was found to occur in the first 5 min of incubation at 4
      degrees C. Once bound to the plate, these pneumocandins could not be removed from
      the plate, either by treatment with 4.0 to 6.0 M urea or by treatment with 4.0 to
      6.0 M guanidine hydrochloride for 24 h at 4 degrees C. The binding ELISA is
      linear with drug concentration and can detect levels of L-733,560 as low as 5
      ng/ml in human plasma. The assay is also useful for quantitating plasma levels of
      related semisynthetic pneumocandins including clinical candidate MK-0991.

PMID- 9574719
TI  - Recurrent catheter-related infection caused by a single clone of Mycobacterium
      chelonae with two colonial morphotypes.
AB  - We describe herein a recurrent catheter-related (Port-A-Cath; Smiths Industries
      Medical Systems [SIMS] Deltec, Inc., St. Paul, Minn.) infection caused by
      multidrug-resistant Mycobacterium chelonae with two colonial morphotypes in a 53
      year-old woman with gastric adenocarcinoma. Four isolates recovered from this
      patient within a 3-month period were found to belong to a single clone on the
      basis of the isolates' identical antibiotypes as determined by the E test and
      their identical random amplified polymorphic DNA patterns.

PMID- 9574718
TI  - Apparent increased prevalence of high-level aminoglycoside-resistant Enterococcus
      durans resulting from false identification by a semiautomated software system.
AB  - Identification of enterococci by using a semiautomated system (PASCO; Difco
      Laboratories, Detroit, Mich.) in the AHEPA University Hospital, Thessaloniki,
      Greece, revealed a high proportion of Enterococcus durans, particularly among
      isolates highly resistant to gentamicin and streptomycin. When 14 isolates were
      further tested by a conventional biochemical scheme and by PCR, all were
      reidentified as Enterococcus faecalis. Antibiotic resistance and pulsed-field gel
      electrophoresis patterns showed that unrelated strains were misidentified.

PMID- 9574720
TI  - Buffered plate antigen test as a screening test for diagnosis of human
      brucellosis.
AB  - Brucellosis in Argentina is currently investigated in bank donor blood by the
      standard plate agglutination test (PAT). This study evaluated the buffered plate
      antigen test (BPA), now used to screen for bovine brucellosis, as a screen for
      human disease. Of 57 sera from patients with culture-confirmed brucellosis, 100%
      were detected with the BPA. Of 142 sera positive by rose bengal (RB) and
      complement fixation (CF), from patients with clinical evidence of brucellosis,
      the BPA detected 100%. Of 307 sera from a nonsymptomatic population that were RB
      and CF negative, the BPA detected 99.67% of the negative sera. The data indicate
      that the BPA is satisfactory compared to the other agglutination tests employed.
      It is an inexpensive and practical screening test and reduces the nonspecific
      reactions detected by the PAT.

PMID- 9574721
TI  - Simplification of a locus-specific DNA typing method (Vir typing) for
      Streptococcus pyogenes.
AB  - We describe a simplification of a highly discriminatory molecular typing method,
      called Vir typing, for Streptococcus pyogenes (D. Gardiner, J. Hartas, B. Currie,
      J. D. Mathews, D. J. Kemp, and K. S. Sriprakash, PCR Methods Appl. 4:288-293,
      1995). The procedure can be completed within a day, is reproducible, and can be
      applied directly to colonies growing on primary culture plates, allowing rapid
      establishment of strain identity in an outbreak.

PMID- 9574722
TI  - Identification of Corynebacterium amycolatum and other nonlipophilic fermentative
      corynebacteria of human origin.
AB  - Four identification tests, proposed in addition to conventional methods, were
      evaluated with 320 fermentative nonlipophilic Corynebacterium strains: growth at
      20 degrees C, glucose fermentation at 42 degrees C, alkalinization of sodium
      formate, and acid production from ethylene glycol. These tests were highly
      discriminant. Corynebacterium amycolatum displayed a unique profile, allowing it
      to be distinguished from similar species, such as C. xerosis, C. striatum, and C.
      minutissimum.

PMID- 9574723
TI  - Association of Providencia alcalifaciens with diarrhea in children.
AB  - It has been demonstrated in previous studies that Providencia alcalifaciens can
      produce diarrhea by an invasive mechanism. In the present study, P. alcalifaciens
      was isolated from the stool specimens of 17 of 814 diarrheal children younger
      than 5 years of age (2.1%) and from those of 4 of 814 matched controls (0.49%) (P
      = 0.004), indicating that the organism is significantly associated with diarrhea.
      However, 71% of P. alcalifaciens-positive diarrheal children had simultaneous
      infections with other recognized enteric pathogens.

PMID- 9574724
TI  - Use of voriconazole in treatment of Scedosporium apiospermum infection: case
      report.
AB  - We report a case of disseminated Scedosporium apiospermum infection in a
      neutropenic patient with acute myeloid leukemia. Due to progression of the
      mycosis after 7 days of amphotericin B lipid complex therapy and to high
      susceptibility of the mold to voriconazole in vitro, the patient was treated with
      intravenous voriconazole. After a few days of therapy, fever disappeared and skin
      lesions improved. However, the patient died after 1 month due to intestinal
      bleeding. Despite a negative outcome, this case seems to indicate a promising
      role for voriconazole in the treatment of S. apiospermum infections.

PMID- 9574725
TI  - Evaluation of a membrane filter assay system, Ortho HCV Ab Quick Pack, for
      detection of anti-hepatitis C virus antibody.
AB  - A simple membrane immunoassay assay system, Quik Pack, for the detection of
      hepatitis C virus antibody was compared with two enzyme-linked immunosorbent
      assays (ELISAs) in a study of 600 serum samples. Quik Pack exhibited excellent
      sensitivity and specificity: 96.0 and 99.7%, respectively, versus the ELISA-2 and
      99.7 and 99.4%, respectively, versus the ELISA-3.

PMID- 9574726
TI  - Isolation of influenza C virus during an outbreak of influenza A and B viruses.
AB  - During the winter of 1996 to 1997 two cases of influenza C were confirmed, one by
      isolation and the second by serology (fourfold increase in hemagglutination
      inhibition antibodies). The cases of influenza C occurred during an outbreak of
      influenza A (H3N2) and B viruses. The positive isolation was from one of three
      throat washings sent to the laboratory, and the other case was from a group of 51
      students participating in a study of influenza virus vaccination. It seems,
      therefore, that influenza C virus should also be considered when examining
      patients with respiratory infections during the influenza season.

PMID- 9574727
TI  - Comparison of the rapid yeast plus panel with the API20C yeast system for
      identification of clinically significant isolates of Candida species.
AB  - The RapID Yeast Plus system (Innovative Diagnostic Systems, Norcross, Ga.) is a
      qualitative micromethod employing conventional tests and single-substrate
      chromogenic tests and having a 4-h incubation period. This system was compared
      with the API20C (bioMerieux Vitek, Hazelwood, Mo.) system, a 24- to 72-h
      carbohydrate assimilation method. One hundred thirty-three clinical yeast
      isolates, including 57 of Candida albicans, 26 of Candida tropicalis, 23 of
      Candida glabrata, and 27 of other yeasts, were tested by both methods. When
      discrepancies occurred, isolates were further tested by the Automated Yeast
      Biochemical Card (bioMerieux Vitek). Germ tube production and microscopic
      morphology were used as needed to definitively identify yeast isolates. The RapID
      Yeast Plus system correctly identified 125 yeast isolates, with an overall
      accuracy of 94% (125 of 133). Excellent correlation was found in the recognition
      of the three yeasts most commonly isolated from human sources. The test was 99%
      (105 of 106 isolates) accurate with C. albicans, C. tropicalis, and C. glabrata.
      The RapID Yeast Plus system compares favorably with the API20C system and
      provides a simple, accurate alternative to conventional assimilation methods for
      the rapid identification of the most commonly encountered isolates of Candida
      species.

PMID- 9574728
TI  - Survey of Klebsiella pneumoniae strains producing extended-spectrum beta
      lactamases: prevalence of SHV-12 and SHV-2a in Korea.
AB  - Fifty-three clinical isolates of extended-spectrum beta-lactamase (ESBL)
      producing Klebsiella pneumoniae collected from three hospitals in Korea were
      investigated for phenotypical and genotypical characterizations. Among these, 39
      strains (74%) were shown by isoelectric focusing to carry SHV-type beta
      lactamases: 27 strains showed the pI 8.2 beta-lactamase, and another 12 strains
      showed the pI 7.6 beta-lactamase. The SHV gene of each of these strains was
      amplified by PCR, followed by nucleotide sequencing analysis. The gene of the pI
      8.2 beta-lactamase was found to be identical to the sequences encoding SHV-12,
      and the gene of the pI 7.6 beta-lactamase was identical to the sequences encoding
      SHV-2a. A total of eight cefoxitin-resistant strains were found to have the
      plasmid-mediated AmpC-type beta-lactamase, with a pI of 8.0, and this was
      confirmed to be CMY-1 beta-lactamase by PCR and hybridization analysis.
      Noteworthy in this study is the fact that SHV-12 and SHV-2a have been the most
      commonly identified SHV-type ESBLs in Korea.

PMID- 9574729
TI  - Comparison of a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5
      [(phenylamino)carbonyl]-2H-t etrazolium hydroxide (XTT) colorimetric method with
      the standardized National Committee for Clinical Laboratory Standards method of
      testing clinical yeast isolates for susceptibility to antifungal agents.
AB  - MICs for clinical Candida and Cryptococcus isolates were determined by a method
      incorporating the colorimetric indicator 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)
      5-[(phenylamino)carbonyl] -2H-tetrazolium hydroxide (XTT), and the results were
      compared with MICs obtained by the National Committee for Clinical Laboratory
      Standards approved standard method (M27-A). One hundred percent of all isolates
      demonstrated agreement within 2 dilutions between the MICs of amphotericin B,
      fluconazole, itraconazole, ketoconazole, and flucytosine obtained by the two
      methods. These data suggest that an XTT-based method could provide a useful means
      for the determination of antifungal susceptibility of yeasts.

PMID- 9574730
TI  - Detection of Leptospira DNA in patients with aseptic meningitis by PCR.
AB  - Samples of cerebrospinal fluid from 103 patients with aseptic meningitis were
      tested by PCR for detection of leptospires, and the results were compared with
      those of the microscopic agglutination test (MAT) and an enzyme-linked
      immunosorbent assay for detection of immunoglobulin M (ELISA-IgM). Of these
      samples, 39.80% were positive by PCR and 8.74 and 3.88% were positive by MAT and
      ELISA-IgM, respectively.

PMID- 9574731
TI  - Number of days required for recovery of mycobacteria from blood and other
      samples.
AB  - From 1991 to 1996, 541 blood samples were tested for the presence of
      mycobacteria; 56 were positive (30 patients, 26 human immunodeficiency virus
      positive). The species found were Mycobacterium avium (41 samples from 18
      patients), Mycobacterium tuberculosis (12 samples from 9 patients), and three
      other species (1 sample each). The average time to detection was 25.23 days
      (22.65 for M. avium and 35.33 for M. tuberculosis). For 10 patients, the blood
      isolate was the only mycobacterium detected (4 M. tuberculosis).

PMID- 9574732
TI  - Rapid detection of species of the opportunistic yeast Trichosporon by PCR.
AB  - Trichosporon species are opportunistic pathogens, associated with a high
      mortality rate in immunocompromised patients. Oligonucleotide primers were used
      to amplify a 170-bp fragment of small-subunit ribosomal DNA of all species in the
      genus Trichosporon by PCR. The primers amplify DNAs of all species in the genus
      Trichosporon, including six causative agents of trichosporonosis. DNAs of other
      medically important yeasts, such as Candida albicans and Cryptococcus neoformans,
      are not amplified by this detection system.

PMID- 9574734
TI  - Evaluation of BBL CHROMagar and CPS ID2 media for detection and presumptive
      identification of urinary tract pathogens.

PMID- 9574733
TI  - Comparison of DNA enzyme immunoassay and line probe assays (Inno-LiPA HCV I and
      II) for hepatitis C virus genotyping.
AB  - Two methods for genotyping hepatitis C virus (DNA enzyme immunoassay [DEIA] and
      line probe assay [Inno-LiPA HCV I and II]) were compared on 120 samples and of
      these 87% were assigned to the same subtype by both assays. There were 15
      subtyping discrepancies which involved 5% of type 1 isolates and 90% of type 2
      isolates. Amplified products from the core and 5' untranslated regions (UTR) were
      sequenced to resolve conflicts. Type 1 discordant samples had a guanosine at
      position -99 in the 5' UTR, a characteristic of genotype 1b, and a core region
      typical of subtype 1a. The eight isolates classified as 2a/2c by LiPA and as
      subtype 2c by DEIA belonged to type 2.

PMID- 9574735
TI  - Susceptibility testing of Bordetella pertussis.

PMID- 9574736
TI  - IS200 insertion between gyrA and rcsC genes in Salmonella typhi.

PMID- 9574737
TI  - Distinctive carbohydrate assimilation profiles used to identify the first
      clinical isolates of Candida dubliniensis recovered in the United States.

PMID- 9574738
TI  - High hopes for new FDA law.

PMID- 9574739
TI  - Accuracy of corneal elevation with four corneal topography systems.
AB  - PURPOSE: To compare the elevation accuracy of placido-based videokeratoscopes
      with a rasterphotogrammetry-based topography system using models of an aspheric
      surface and a simulated myopic ablation. METHODS: Test surfaces representative of
      normal corneas and corneas after excimer ablation were fabricated from a material
      measurable using both reflective (placido) and projective (rasterstereographic)
      systems. The "normal" surface was a rotationally symmetric asphere, while the
      simulated photorefractive keratectomy ablation had a central 5.5 mm diameter
      clear zone with a 1 mm blend radius to eliminate surface discontinuity. The
      surfaces were measured with their axes of symmetry aligned with the instrument
      axis, and again with their axes tilted downward by 10 degrees to produce a
      nonsymmetric shape. RESULTS: All of the topography systems performed reasonably
      well in measuring the aspheric surface, with root mean square elevation error
      ranging from 1.2 to 14.3 microm. The rasterstereographic system had a root mean
      square error of 4.7 microm on the simulated ablation, while the placido systems
      had root mean square errors of 10.6 to 29.5 microm. Tilting the surfaces did not
      significantly alter the results. CONCLUSIONS: The tested placido
      videokeratoscopes do not provide reliable elevation data for shapes that have
      nonlinear changes in curvature. This may have serious implications if these
      systems are used for postoperative analysis or contact lens fitting on corneas
      that have been modified by refractive procedures.

PMID- 9574740
TI  - Clear lensectomy and intraocular lens implantation for hyperopia from +7 to +14
      diopters.
AB  - BACKGROUND: Our results of clear lens extraction and intraocular lens
      implantation to correct hyperopia from +6.75 to +13.75 D are presented, as well
      as evaluation of two intraocular lens calculation formulae. METHODS: Clear lens
      extraction and posterior chamber intraocular lens implantation was performed in
      35 normally sighted eyes of 21 patients with a mean baseline hyperopic spherical
      equivalent refraction of +9.19 +/- 0.34 D (range +6.75 to +13.75 D). The
      refractive goal was -1.50 D, using the SRK II formula in 17 eyes and the SRK-T
      formula in 18 eyes. Follow-up was up to 5 years. RESULTS: Mean uncorrected visual
      acuity after surgery was 0.8 (range 0.5 to 1.0). Stability of refraction was
      noted from the second month after surgery. No eyes lost any lines of spectacle
      corrected visual acuity. Using the SRK II formula, 100% of eyes were within +/
      1.00 D of emmetropia and with the SRK-T formula, 83.3% for a combined 91.4% of
      eyes within +/-1.00 D of emmetropia. One eye required intraocular lens exchange
      and another eye required photorefractive keratectomy for myopia. Both procedures
      were necessitated by an intraocular lens miscalculation of more than +/-2.00 D.
      Nineteen eyes (54.2%) developed posterior capsular opacification and were treated
      with Nd:YAG laser capsulotomy. CONCLUSION: Clear lens extraction is a safe,
      effective, and predictable procedure for the treatment of hyperopia from +6.75 to
      +13.75 D. The SRK II formula proved slightly superior to the SRK-T in intraocular
      lens calculation when using the "-1.50 D rule."

PMID- 9574741
TI  - Results and complications of laser in situ keratomileusis by experienced
      surgeons.
AB  - PURPOSE: To identify intraoperative and early postoperative adverse events and
      complications that may be encountered after the laser in-situ keratomileusis
      (LASIK) learning process. METHODS: One hundred sixty-nine consecutive eyes of 108
      patients who had LASIK by a surgeon experienced in LASIK were studied. All
      intraoperative and early postoperative adverse events and complications were
      noted. Patients were examined at 1 day and 1 to 3 months after surgery. Six
      baseline refractive groups were studied: high myopia with astigmatism (-10.25 to 
      17.50 D; 18 eyes), moderate myopia with astigmatism (-6.00 to -9.50 D; 31 eyes),
      low myopia with astigmatism (-0.75 to -5.87 D; 81 eyes), mixed astigmatism (-0.25
      to +0.50 D; 6 eyes), low to moderate hyperopia with astigmatism (+1.00 to +3.75
      D; 19 eyes), and high hyperopia with astigmatism (+4.25 to +7.37 D; 12 eyes).
      Seventy-eight percent (132 eyes) had a primary LASIK procedure; 22% (37 eyes) had
      LASIK after previous refractive surgery. Primary and secondary LASIK procedures
      were analyzed together. The Nidek EC-5000 or the Chiron PlanoScan excimer lasers
      were used. RESULTS: The most commonly observed adverse intraoperative events were
      minor corneal bleeding (3%) and thin flap (1%). The most commonly observed
      postoperative events were punctate epithelial keratopathy (6%) and small
      epithelial defect 1 day after surgery (5%). The most serious complication
      occurred in three eyes with preoperative high hyperopia (spherical equivalent
      refraction greater than +4.00 D) in which corneal topographic abnormalities
      resulted. At last examination, mean postoperative spherical equivalent refraction
      was less than +1.00 D in all groups. Spectacle-corrected visual acuity was 20/20
      in 70 eyes (41%) and 20/25 or better in 119 eyes (70%). Loss of spectacle
      corrected visual acuity of two or more lines occurred in five eyes (3%), three of
      which had preoperative high hyperopia with abnormal postoperative corneal
      topography. CONCLUSION: Our prospective study should help LASIK surgeons gauge
      their expectations of intraoperative and early postoperative complications.
      Surgeons should proceed cautiously when treating patients with high hyperopia,
      because a higher incidence of loss of spectacle-corrected visual acuity may be
      encountered postoperatively.

PMID- 9574742
TI  - Multiple photorefractive keratectomy retreatments for myopia.
AB  - PURPOSE: To examine the outcome of multiple photorefractive keratectomy
      retreatments by the excimer laser on eyes treated for myopia and myopic
      astigmatism. METHODS: We present 980 of 1218 (80%) consecutive eyes treated with
      a VISX 20/20 excimer laser that were available for follow-up. Thirteen eyes of 13
      individuals were retreated twice using the same VISX excimer laser because of
      refractive regression. Epithelium was mechanically removed in the initial
      treatment and subsequent retreatment of all the eyes. No increased difficulty was
      noted upon removing the epithelium on subsequent retreatments. The aim in both
      the initial and subsequent treatments was to correct 100% of the refractive
      error. RESULTS: Eyes with higher amounts of myopia and astigmatism were more
      likely to require multiple retreatments. Seven eyes (54%) attained a spectacle
      corrected visual acuity of 20/20 or better. Twelve eyes (92%) attained a
      spectacle-corrected visual acuity of 20/40 or greater following the second
      retreatment. The amount of astigmatism corrected was improved in 10 of the 13
      eyes with an average improvement of 1.90 D of cylinder. Only one patient
      experienced a haze score of 3 or more following retreatment. CONCLUSION: There is
      a subgroup of patients who require multiple PRK retreatments for myopic
      regression. A good visual outcome may be obtained with minimal haze.

PMID- 9574743
TI  - Treatment of corneal dystrophies with phototherapeutic keratectomy.
AB  - PURPOSE: To evaluate the excimer laser as a surgical instrument for treatment of
      corneal dystrophies. METHODS: Excimer laser photoablation was performed with the
      Summit UV 200 and VISX 20/20 excimer lasers on 30 eyes of 21 patients with
      different types of corneal dystrophies; phototherapeutic keratectomy (PTK) on 28
      eyes (20 patients) and photorefractive keratectomy (PRK) on two eyes (one
      patient). The treatment goals were to improve visual acuity (26 eyes of 18
      patients), heal recurrent corneal erosions (eight eyes of five patients), and
      treat fluctuating refraction and visual acuity (three eyes of two patients). Mean
      follow-up was 37 months (range 24 to 54 mo). The dystrophy groups included: map
      dot-fingerprint (nine eyes of seven patients), lattice type I (five eyes of four
      patients), lattice type II (two eyes of one patient), granular (five eyes of
      three patients), central crystalline (four eyes of three patients), Reis
      Bucklers' (two eyes of one patient), Meesmann's (two eyes of one patient), and
      Fuchs' endothelial (one eye). RESULTS: In 22 of 26 eyes (84.6%) there was an
      improvement in spectacle-corrected visual acuity after 6 to 12 months. This
      improvement remained stable in 18 eyes (69.2%). Pronounced recurrences of
      dystrophic changes with reduction in visual acuity were seen in three eyes of two
      patients: lattice type II (two eyes) and granular (one eye). In one eye with
      Fuchs' endothelial dystrophy, there was a recurrence of subepithelial fibrosis
      which had been previously removed. In eight of eight eyes (100%) treated for
      recurrent corneal erosions (map-dot-fingerprint, Meesmann's, and lattice type I),
      the erosions healed shortly after treatment and did not recur. Preoperative
      fluctuating refraction stabilized in three of three eyes (100%) with mapdot
      fingerprint after treatment. The mean hyperopic refractive shift was +2.55 +/-
      2.16 D. In none of the patients did the treatment per se lead to a decrease in
      spectacle-corrected visual acuity or any corneal surface problems. CONCLUSION: In
      corneal dystrophies with epithelial and anterior stromal opacities, excimer laser
      PTK may be successful in improving vision and healing recurrent corneal erosions
      over the long term.

PMID- 9574744
TI  - Novel approaches to correction of presbyopia with laser modification of the
      crystalline lens.

PMID- 9574745
TI  - Continuous non-contact corneal pachymetry with a high speed reflectometer.
AB  - PURPOSE: We developed an instrument that permits non-contact, continuous, high
      speed and high precision monitoring of corneal thickness and tested the stability
      and reproducibility of measurements made over extended time periods and under
      various conditions of low surface reflectivity encountered during protracted
      exposure of the unmoistened corneal surface to ambient air. METHODS: The optical
      pachymeter (basic component of a broad-band, all-fiber Michelson interferometer)
      was used to monitor changes in the central corneal thickness of enucleated
      porcine eyes. Measurements were performed on three groups of eight eyes, each
      with different surface characteristics: intact epithelium, mechanically abraded
      epithelium, and 90 microm excimer laser keratectomy. Corneal thickness was
      monitored continuously with values recorded every 2 to 3 minutes for periods up
      to 1 hour in the absence of surface rinsing. RESULTS: The thicknesses of all
      unmoistened corneas could be monitored with a precision of 1 microm (ascertained
      using a calibration glass plate and a living human cornea) over the entire
      observation period. Under ambient air conditions, deturgescence occurred in each
      case, and ranged from 1 to 5 microm/min. The rate of corneal thinning was fairly
      constant during the first 15 minutes of monitoring, but was nonlinear thereafter.
      Corneas with an intact epithelium had the lowest thinning rate with only 10% of
      the original thickness lost during the course of 1 hour. Deturgescence increased
      to 25% in corneas that had mechanical removal of the epithelium and to 28.5% in
      those that had an anterior excimer laser keratectomy, during a similar time
      period. CONCLUSION: With this new interferometric method, continuous, non-contact
      measurement of corneal thickness is possible to within a precision of 1 microm
      for periods up to 1 hour, even under the modified surface conditions after
      photoablative keratectomy. This device may be useful for on-line monitoring of
      ablation depths during such procedures.

PMID- 9574746
TI  - Late onset of haze associated with viral keratoconjunctivitis following
      photorefractive keratectomy.
AB  - BACKGROUND: To report a newly recognized cause of late onset of corneal haze
      following photorefractive keratectomy (PRK). METHODS: A 35-year old woman who
      underwent uneventful PRK and subsequently developed viral keratoconjunctivitis 1
      year after treatment. RESULTS: During resolution of the viral
      keratoconjunctivitis, the patient developed extensive central corneal
      subepithelial infiltrates and anterior stromal fibrosis in the PRK ablation zone.
      More than 1 year after the initial infection, the central subepithelial fibrosis
      persisted, complicated by myopic regression, central steep island on
      videokeratography, and loss of five lines of spectacle-corrected visual acuity.
      By the end of the second year after the infection, visual acuity had improved
      with disappearance of the central steep island on videokeratography. However, the
      myopic regression and subepithelial fibrosis remained. CONCLUSION: Patients who
      undergo PRK may be at greater risk of visual loss following viral
      keratoconjunctivitis secondary to persistent subepithelial infiltrates and/or
      stromal fibrosis within the PRK treatment zone.

PMID- 9574747
TI  - Effects of gamma-interferon on keratocyte-induced collagen gel contraction and
      keratocyte proliferation.
AB  - PURPOSE: Gamma-interferon has been shown to be an effective immunoregulatory
      polypeptide that can modulate fibroblastic response. We investigated the effects
      of gamma-interferon on keratocyte proliferation and keratocyte-induced collagen
      gel contraction. METHODS: Gamma-interferon in concentrations of 0.01, 1, 100, and
      1000 U/ml of media was added to keratocytes embedded in polymerized type I
      collagen and the gel area was measured after 5 days with an image analysis
      system. The rate of keratocyte proliferation within and outside the collagen gel
      under the influence of gamma-interferon was also investigated. RESULTS:
      Keratocyte-induced collagen gel contraction was significantly inhibited at all
      concentrations above 0.01 U/ml. The keratocyte proliferation was not affected by
      low and moderate concentrations and was significantly stimulated at concentration
      of 1000 U/ml. CONCLUSION: Keratocyte-induced collagen gel contraction is
      inhibited by gamma-interferon and the mechanism of this effect is not inhibition
      of keratocyte proliferation by gamma-interferon.

PMID- 9574748
TI  - Corneal interface abscess after excimer laser in situ keratomileusis.
AB  - Laser in situ keratomileusis (LASIK) carries the risk of infection. We report a
      case culture-negative interface abscess following LASIK that was successfully
      treated with antibiotics and povidone iodine.

PMID- 9574749
TI  - A 10-year review of a minimally invasive technique for the correction of pectus
      excavatum.
AB  - PURPOSE: The aim of this study was to assess the results of a 10-year experience
      with a minimally invasive operation that requires neither cartilage incision nor
      resection for correction of pectus excavatum. METHODS: From 1987 to 1996, 148
      patients were evaluated for chest wall deformity. Fifty of 127 patients suffering
      from pectus excavatum were selected for surgical correction. Eight older patients
      underwent the Ravitch procedure, and 42 patients under age 15 were treated by the
      minimally invasive technique. A convex steel bar is inserted under the sternum
      through small bilateral thoracic incisions. The steel bar is inserted with the
      convexity facing posteriorly, and when it is in position, the bar is turned over,
      thereby correcting the deformity. After 2 years, when permanent remolding has
      occurred, the bar is removed in an outpatient procedure. RESULTS: Of 42 patients
      who had the minimally invasive procedure, 30 have undergone bar removal. Initial
      excellent results were maintained in 22, good results in four, fair in two, and
      poor in two, with mean follow-up since surgery of 4.6 years (range, 1 to 9.2
      years). Mean follow-up since bar removal is 2.8 years (range, 6 months to 7
      years). Average blood loss was 15 mL. Average length of hospital stay was 4.3
      days. Patients returned to full activity after 1 month. Complications were
      pneumothorax in four patients, requiring thoracostomy in one patient; superficial
      wound infection in one patient; and displacement of the steel bar requiring
      revision in two patients. The fair and poor results occurred early in the series
      because (1) the bar was too soft (three patients), (2) the sternum was too soft
      in one of the patients with Marfan's syndrome, and (3) in one patient with
      complex thoracic anomalies, the bar was removed too soon. CONCLUSIONS: This
      minimally invasive technique, which requires neither cartilage incision nor
      resection, is effective. Since increasing the strength of the steel bar and
      inserting two bars where necessary, we have had excellent long-term results. The
      upper limits of age for this procedure require further evaluation.

PMID- 9574750
TI  - Prenatal magnetic resonance imaging enhances fetal diagnosis.
AB  - BACKGROUND: Ultrasound (US) evaluation of some fetal anomalies provides limited
      information. Anatomic details that affect prognosis and selection for fetal
      therapy, such as liver herniation and pulmonary hypoplasia in congenital
      diaphragmatic hernia (CDH) and airway patency in giant neck masses, may be
      difficult to delineate using conventional sonographic methods. The authors
      evaluated the utility of prenatal magnetic resonance imaging (MRI) with new
      ultrafast imaging sequences in the diagnosis and management of fetal anomalies.
      METHODS: From April 1996 to April 1997 45 MRI scans were performed in 31 pregnant
      women with an US diagnosis of a fetal anomaly. The US diagnoses included CDH,
      giant neck masses, lung masses, abdominal and pelvic abnormalities, twin
      anomalies, and central nervous system (CNS) anomalies. The fetuses ranged in age
      from 18 to 39 weeks' gestation (mean, 28.7 weeks). Using a 1.5-T magnet, a
      variety of ultrafast imaging sequences were performed including fast gradient
      echo, half-fourier single shot turbo spin-echo (Haste) and echo-planar imaging
      yielding images with T1 to T2 type weighting. RESULTS: With CDH, MRI demonstrated
      liver herniation into the chest in 11 of 14 cases. In four cases, US findings had
      not been definitive. In two cases of CDH detected by MRI, the primary diagnosis
      by US had been congenital cystic adenomatoid malformation (CCAM). With lung
      masses, MRI accurately distinguished between CCAM and bronchopulmonary
      sequestration (BPS). For giant neck masses with potential airway obstruction, MRI
      scans permitted differentiation of teratoma from cystic hygroma and allowed
      delineation of fetal airway involvement. The accurate anatomic evaluation
      facilitated planning for the ex utero intrapartum treatment (EXIT) procedure, a
      technique for securing the airway while the term fetus is still on placental
      support. With huge abdominal masses such as enterogenous cyst and lymphangioma,
      MRI scanning clarified the diagnosis. Fourteen of the 31 (45%) patients underwent
      fetal treatment after US and MRI evaluation. CONCLUSIONS: Prenatal MRI enhances
      fetal anatomic evaluation and facilitates perinatal management and family
      counseling. Ultrafast imaging sequence MRI is helpful to corroborate and refine
      US diagnoses. Fetal MRI is a valuable adjunct to US for prenatal diagnosis before
      fetal surgical intervention for selected life-threatening birth defects.

PMID- 9574751
TI  - In vivo growth of transplanted genetically altered intestinal stem cells.
AB  - PURPOSE: Intestinal stem cell transplantation is a potential method of delivering
      genes to the small intestine. The authors have previously demonstrated the
      survival of transfected intestinal stem cells implanted into the rat small
      intestine. This study examines the growth of genetically altered intestinal stem
      cells that were grown on a polycarbonate membrane and implanted into the rat
      small intestine. METHODS: The IEC6 rat intestinal cell line serves as a model for
      intestinal stem cells. A subclone of the IEC6 cells was developed that stably
      expresses the lac Z gene introduced by a retroviral vector. The transfected cells
      were seeded at 500,000 cells/cm2 on a polycarbonate membrane. In 15 male Sprague
      Dawley rats, a 0.75-cm enterotomy was created on the antimesenteric side of the
      small intestine 5 cm distal to the ligament of Treitz. A 0.5-cm2 segment of the
      membrane was sutured over the enterotomy with the cells facing away from the
      intestinal lumen. A segment of the omentum was wrapped around the patched
      enterotomy and sutured to the serosa. Three and 7 days after implantation, the
      implanted cells were retrieved, then fixed and stained with an X-gal solution.
      The number of cells was determined from the intensity of the X-gal staining. In
      five of the rats, frozen sections of the enterotomy sites were examined after
      staining with X-gal. RESULTS: All 15 rats survived the implantation procedure.
      Initially, 0.32 +/- 0.11 million cells were implanted. At both 3 and 7 days, the
      enterotomy site still contained viable transfected cells. The number of viable
      cells increased substantially to 1.52 +/- 0.46 and 3.52 +/- 1.87 million cells at
      3 and seven days, respectively (P < .05). CONCLUSIONS: The polycarbonate membrane
      served as a good vehicle to efficiently deliver genetically altered intestinal
      stem cells to the small intestine. The transplanted cells continued to grow and
      stably expressed the gene product. This ex vivo approach to gene therapy has
      considerable therapeutic potential.

PMID- 9574752
TI  - Hyaluronan induces scarless repair in mouse limb organ culture.
AB  - BACKGROUND/PURPOSE: Wounded fetal mouse limbs harvested from two distinct time
      points in gestation heal differently in organ culture. The healing of a
      gestational day 14 limb is by scarless repair, whereas gestational day 18 (gd 18)
      limbs heal by scarring. The persistence of elevated levels of hyaluronic acid
      (HA) is a major difference in the extracellular matrix of scarless repair. The
      purpose of this study was to demonstrate that chronic additions of HA to
      incisional wounds of gd 18 limbs induces scarless repair. METHODS: Time-dated
      pregnant CD-1 mice (term, 20 days) were killed on gestational day 18 and fetuses
      were harvested via laparotomy. A through and through stab wound was made in each
      forelimb with a 1-mm microscapel, and the wound was closed with a single 10-0
      nylon suture. The forelimbs were amputated at the level of the shoulder and
      placed in organ culture. Daily medium changes with 1 mL of BGJb (devoid of serum)
      were made. Half the cultures received 10 microL of HA (4 mg/mL) directly to the
      wound site with each medium change. The other half of the cultures received 10
      microL of phosphate-buffered saline (PBS-control). At day 7, the limbs were
      harvested, fixed in methyl Carnoys solution, paraffin embedded, and 5-microm
      serial sections cut. The sections were stained with H&E or Sirius red/fast green.
      The sections were viewed in a blinded fashion by two observers. Suture defined
      the wound site, and the sections were graded for healing by scarring. RESULTS:
      Minimal limb growth occurred in both control and HA-treated limbs. Grossly, both
      control and treated limbs healed incisional wounds by 7 days in culture. Limbs
      from both treatment and control groups showed viability by microscopic analysis.
      The limbs treated with HA had no appreciable scar morphologically in sections in
      which epithelial dimpling and suture were evident. The orientation of the
      collagen fiber bundles in the control wounds were in parallel arrays
      perpendicular to the incision. The orientation of the collagen fiber bundles in
      the HA-treated limbs had a basket weave pattern that was indistinguishable from
      unwounded dermis. The direct repeated additions of HA to healing organ cultured
      limb explants of gestational day 18 fetal mice promoted scarless repair.
      CONCLUSIONS: This result demonstrates that chronic elevation of HA in the
      microenvironment of a wound affects healing by promoting the deposition of a more
      dermal-like connective tissue matrix in the wound site. The maintenance of
      elevated levels of HA could have utility in the clinical setting to improve the
      organization of connective tissue, leading to the reduction of scar
      complications.

PMID- 9574753
TI  - TBJ murine neuroblastoma resists dibutyryl cyclic AMP-induced differentiation and
      effects on metalloproteinase secretion.
AB  - BACKGROUND: Nonmetastatic C1300 murine neuroblastoma and TBJ, a metastatic
      variant, exhibit different mechanisms of metastasis and invasion. METHODS: In
      this study, they were examined for response to 1 mmol/L dibutyryl cyclic AMP in
      vitro. RESULTS: (1) dCAMP induced morphological differentiation in 20% to 40% of
      C1300 cells, whereas TBJ resisted differentiation. (2) Untreated TBJ expressed 92
      kDa metalloproteinase, whereas C1300 expressed none. These results were not
      affected by dCAMP. (3) Growth curves of untreated C1300 and TBJ were exponential.
      Dibutyryl CAMP induced a plateau in C1300 growth that was confirmed by increased
      S-phase cells by cell cycle analysis. CONCLUSIONS: TBJ growth was unaffected by
      dCAMP. Apoptosis, as assayed by Hoechst-merocyanine staining test, was not
      involved in the growth plateau.

PMID- 9574754
TI  - Are scintiscans accurate in the selection of reflux patients for pyloroplasty?
AB  - BACKGROUND: Gastric emptying scintiscans are currently used to select reflux
      patients for added pyloroplasty at the time of fundoplication. The accuracy of
      this scan selection approach has been assumed. If preoperative scintiscans do not
      reliably predict postfundoplication gastric emptying, however, the decision to
      add pyloroplasty to the fundoplication operation may be inappropriate and even
      harmful. METHODS: The authors studied 27 children prospectively before and after
      gastric fundoplication. Gastric emptying at 60 minutes was measured by double
      isotopic labeling of liquid (111In) and solid (99mTc) phases of a test meal
      specifically designed for label fixation. The authors' question involved the
      accuracy of preoperative gastric scintiscans in predicting postfundoplication
      delay of gastric emptying (DGE). An evaluation of pyloroplasty as an effective
      treatment for DGE was not part of the study design. Pyloroplasty was performed as
      a secondary operation in three of the study children, however, because they
      persisted with unrelieved symptoms of retching, fullness, and abdominal
      discomfort. Scintiscan-documented postfundoplication delay in gastric emptying
      was present in all three patients at 18, 58, and 12 weeks, respectively.
      Additional scintiscans were performed in these patients after pyloroplasty.
      RESULTS: Gastric emptying of solids at 60 minutes did not show a significant
      change after a gastric fundoplication operation, although the trend was in the
      direction of a decrease (paired t test, P= .13). Liquid emptying at 60 minutes,
      however, was significantly increased (paired t test, P = .01). The variation in
      values between patients was wide, and the correlation between pre- and
      postoperative study results in the same patient was poor (r2 = 0.337 for solids
      and r2 = 0.116 for liquids). Most unexpectedly, scintiscans after
      postfundoplication pyloroplasty in the three patients with persistent symptoms
      showed no improvement in delayed gastric emptying on repeat scintiscan 42 to 117
      weeks later. CONCLUSIONS: The data suggest that preoperative scintiscan evidence
      for postfundoplication DGE is probably accurate for solid emptying but not for
      liquids, at least as measured by the double isotope methodology of our study.
      Preoperative scintiscans that use a liquid phase label only may be highly
      misleading for the prediction of postfundoplication DGE. Furthermore,
      pyloroplasty may not be useful as treatment even when postfundoplication delay in
      gastric emptying can be accurately anticipated or confirmed. A fundamental
      motility disorder of the gastric body seems to be more important than muscular
      resistance at the gastric outlet as a cause for postfundoplication DGE, and the
      most effective treatment approach remains unclear.

PMID- 9574755
TI  - Isolated single umbilical artery anomaly and the risk for congenital
      malformations: a meta-analysis.
AB  - BACKGROUND/PURPOSE: Single umbilical artery (SUA) is an associated finding in
      many chromosomal abnormalities and congenital malformations. However, SUAcan also
      be seen as an isolated finding. The extent of diagnostic investigation and follow
      up needed in infants with SUA as an isolated finding has long been debated. In
      this study the authors examined this issue by an analysis of the published papers
      concerning SUA anomaly. METHODS: A meta-analysis of 37 studies related to SUA
      published over a 40-year period was performed. Eleven of 37 studies were
      considered group 1 because the diagnosis of SUA was made using specimens obtained
      from early abortuses, fetal deaths, or autopsies. The remaining 26 studies were
      considered group 2 because the diagnosis of SUA was made from examining placental
      and umbilical cord specimens obtained from live-born infants or by examination of
      the umbilicus soon after birth. RESULTS: The mean (and 95% CI) SUA incidence was
      2.13% (1.92%, 2.34%) in group 1, and 0.55% (0.44%, 0.66%) in group 2. The mean
      incidence of congenital malformation associated with SUA was 66.3% (67.7%, 70.8%)
      in group 1, and 27% (21.6%, 32.3%) in group 2; these differences were significant
      (P< .05). In 7 of 26 group 2 studies, additional urologic investigations were
      performed in 204 infants who had an isolated SUA anomaly. Thirty-three of these
      204 infants (16.2%, 95% CI, 7.7%, 25.6%) had some form of renal anomaly, but in
      18 of 33 (54.5%) the anomalies were minor or self limiting. A cost-versus-benefit
      analysis showed that 14 isolated SUA cases need to be investigated to detect one
      major renal malformation; however, the value of detecting them early remained
      unclear because most of the anomalies would be apparent with good pediatric
      follow-up. CONCLUSIONS: When SUA is an isolated anomaly in an otherwise healthy
      infant, there is a slight increase in the risk for renal malformations. This
      association is of similar magnitude to the coexistence of another anomaly with
      the presence of one anomaly. Most renal anomalies in isolated SUA cases are minor
      and self limiting, and even major anomalies are no different from those that are
      diagnosed during routine pediatric follow-up in otherwise healthy infants.
      Therefore, unless additional risk factors for malformations exist, the current
      data do not justify extensive urologic radiographic investigations in
      asymptomatic newborns having an isolated SUA anomaly.

PMID- 9574756
TI  - Interstitial hernia: a diagnostic dilemma in infants and children.
AB  - The features of the rare interstitial hernia, as seen in four children, are
      described. All were boys ranging in age from 7 days to 7 years. The presenting
      sign was swelling in the right side of the abdomen associated with undescended
      testis. The hernias arose at the deep inguinal ring and expanded superiorly
      between the internal and external oblique muscles. Repair involved a standard
      herniotomy and orchidopexy through an oblique inguinal incision-except in one
      patient with a vanishing testis. The importance of being aware of this rare type
      of hernia is stressed.

PMID- 9574757
TI  - Firearm ownership in households with children.
AB  - BACKGROUND/PURPOSE: Increased morbidity and mortality rates in children injured
      by firearms has been well documented during this past decade. The aim of this
      study was to determine the socioeconomic factors affecting firearm ownership in
      families with children living in suburban/rural versus inner-city environments,
      and to identify predictors of firearm ownership in these families. METHODS:
      Parents of children less than 19 years old seen in a suburban (n = 751) or inner
      city hospital (n = 406) anonymously completed a questionnaire regarding firearm
      ownership. RESULTS: Firearm ownership was 54% in rural locations, versus 18%
      among inner-city residents (P< .05). Firearm ownership in white households was
      45% versus 20% in African-American households (P< .05). Mean number of all types
      of firearms in white households was 3.38 versus 1.78 in black households (P<
      .001). Firearm ownership was 19% in the less than $20,000 income bracket,
      significantly lower than households with greater incomes, and was significantly
      lower in households in which parents had the least education (19.7%) versus those
      with college degrees (38.5%; P< .05). Firearm owners of rifles and shotguns
      significantly more often cited hunting, collection, and target shooting as
      reasons for owning firearms, in contrast to revolver owners who cited protection
      and collection as reasons for firearm ownership (P < .05). CONCLUSIONS: Firearm
      ownership is higher in rural, caucasian versus inner-city African-American
      residents and is significantly less in households with lower income and
      educational levels. Significant predictors for firearm ownership were number of
      parents in households, educational level of parents, and population of residence.

PMID- 9574758
TI  - What is the relationship between spermatozoa per milliliter at adulthood and the
      tubular fertility index at surgical age for patients with cryptorchidism?
AB  - PURPOSE: The aim of this study was to find out the relationship in the patient
      with cryptorchidism between the number of spermatogonia at surgical age and
      spermiogram data at adulthood. METHODS: Between 1971 and 1996 the authors
      surgically treated 1,550 children for 2,249 undescended testis. In 21 unilateral
      and 41 bilateral cryptorchidism patients, both testis were biopsied at surgical
      procedure during childhood. We currently have spermiogram data for a patient at
      adulthood. RESULTS: By using the best Tubular Fertility Index (TFI) figures of
      both testis, the Sperman correlation index between the two parameters is r =
      0.22, statistically nonsignificant. The TFI test sensitivity is 0.68 and the
      specificity is 0.60. The likehood ratio for a positive test result is 0.84 and
      the likehood ratio for a negative test result is 0.37. CONCLUSION: Although the
      authors have only one spermiogram, and there are few cases, they suspect the TFI
      is not a good index to predict the potential fertility in cryptorchidism
      patients.

PMID- 9574759
TI  - Direct bypassing of extrahepatic portal venous obstruction in children: a new
      technique for combined hepatic portal revascularization and treatment of
      extrahepatic portal hypertension.
AB  - BACKGROUND: Decompression of extrahepatic portal hypertension by directly
      bypassing the thrombosed portal vein has never been reported in cases of children
      with idiopathic (or neonatal) portal vein obstruction and cavernoma. METHODS:
      Seven children (15 years or younger) with portal vein obstruction requiring
      surgical decompression (urgently in two cases), and in whom preoperative Doppler
      had shown that the intrahepatic portal branches were hypoplastic but free of
      thrombus, were included in a pilot study. The cavernoma was bypassed by
      interposing a venous jugular autograft between the superior mesenteric vein and
      the distal portion of the left portal vein. Patients received follow-up using
      routine clinical parameters, upper gastrointestinal endoscopy, and Doppler
      ultrasound. RESULTS: The mesenterico-portal bypass restored a direct
      (physiological) hepatopetal portal flow. The operation resulted in effective
      portal decompression as demonstrated by decrease of the pressure gradient, rapid
      regression of clinical signs of portal hypertension, and definitive control of
      bleeding. CONCLUSIONS: This study shows that direct bypassing of portal cavernoma
      is possible and results in effective portal decompression. Restoration of the
      hepatic portal flow is a major advantage compared with conventional surgical
      shunting procedures. This new technique is potentially applicable to two thirds
      of children with portal vein thrombosis and should be considered when shunting
      procedures are indicated.

PMID- 9574760
TI  - Surgical treatment of diaphragmatic eventration caused by phrenic nerve injury in
      the newborn.
AB  - BACKGROUND: Phrenic nerve palsy in infants and young children usually results
      from birth injury or iatrogenic damage. The newborn almost invariably presents
      with severe respiratory distress, diaphragmatic elevation, and paradoxical
      movement at the affected side. METHODS/RESULTS: In this retrospective analysis a
      group of 23 patients below the age of 1 year with an obstetric or postoperative
      phrenic nerve injury was studied and compared with cases in the literature. All
      patients were admitted between 1986 and 1997 to the Pediatric Surgical Center,
      Amsterdam. Thirteen of 18 patients with an obstetric phrenic nerve injury
      underwent plication of the diaphragm after an average observation period of 100
      days. In the remaining five children with an obstetric phrenic nerve injury,
      spontaneous recovery appeared within 1 month. Only one of five patients with a
      phrenic nerve palsy after a cardiac surgical procedure underwent plication of the
      diaphragm. Fifteen of the 34 patients described in the literature underwent
      plication of the diaphragm after an average of 54 days. CONCLUSIONS: If after 1
      month no spontaneous recovery of the diaphragmatic paralysis caused by a phrenic
      nerve injury occurs, plication of the diaphragm is indicated. This operation
      proved to be successful for relief of symptomatic phrenic nerve injury in all
      cases. If the condition of the patient clinically deteriorates during this first
      month of life, the patient should be operated on immediately.

PMID- 9574761
TI  - Embryology of esophageal atresia in the adriamycin rat model.
AB  - PURPOSE: The aim of this study was to describe the dysmorphogenetic process
      leading to esophageal atresia and tracheoesophageal fistula (EA + TEF) in the
      recently developed Adriamycin model of the malformation. METHODS: Time-mated
      pregnant rats were given either Adriamycin (1.75 mg/kg intraperitoneally) or
      saline on days 6 to 9 of gestation, and their embryos recovered on days 12, 12.5,
      and 13 were serially sectioned in the transversal plane and studied
      microscopically after H&E and PAS staining. The findings were compared with those
      of age-matched untreated embryos. RESULTS: All untreated and saline embryos were
      normal, whereas 49% of Adriamycin embryos had foregut malformations.
      Tracheoesophageal separation was complete on day 12 in control embryos, whereas 9
      of 10 Adriamycin-exposed embryos had a common esophagotrachea with low emergence
      of the bronchi at that stage. This pattern had evolved into that of a regular EA
      + TEF in all nine malformed embryos by day 13. On day 12.5, esophagotrachea was
      found in 6 of 13 and EA + TEF in 5 of 13 embryos. Two had less well-defined
      malformations. CONCLUSIONS: Esophagotrachea equivalent to complete
      tracheoesophageal cleft is the first step leading to EA + TEF in this model. The
      full-blown malformation is finally acquired by partial loss of the posterior wall
      of the foregut, which tapers-off in the mediastinal mesenchyme and respiratory
      differentiation of the anterior wall down to the level of bronchial bifurcation,
      where it constitutes the fistula and the distal esophagus.

PMID- 9574762
TI  - The ontogeny of innervation of the human pylorus.
AB  - PURPOSE: The aim of this study was to document the vagal innervation and
      expression of neuropeptides, neuronal nitric oxide synthase (nNOS), and neural
      cell adhesion molecule (NCAM) in the neuromuscular system of the developing human
      pylorus. METHODS: Specimens of human pylorus (n = 54; age range, 8 weeks'
      gestation to 6 months postnatal) were studied. Vagal innervation was determined
      by Dil autofluorescence. A wide range of neuropeptides, NCAM, and the neural
      isoform of NOS were examined by immunohistochemistry. RESULTS: Vagal innervation
      was first recognized in the myenteric plexus in the 12-week-old fetus as was
      vasoactive intestinal polypeptide (VIP) expression. Neuropeptides were present
      from 8 weeks' gestation and appeared to be expressed progressively from the
      adventitia toward the mucosa and showed an adultlike profile by 23 weeks'
      gestation. A craniocaudal pattern of expression was noted for VIP and nNOS. Alpha
      smooth muscle actin was expressed by muscle fibers of the muscularis propria from
      8 weeks and the muscularis mucosae by 14 weeks. All the isoforms of NCAM examined
      were expressed from 8 weeks in the muscularis propria and by 12 weeks in the
      submucosa. CONCLUSION: The expression of the antigens studied correlated with the
      gestational age and development of the pylorus.

PMID- 9574763
TI  - Morphometric aspects of the submucous plexus in whole-mount preparations of
      normal human distal colon.
AB  - BACKGROUND/PURPOSE: The diagnosis of intestinal neuronal dysplasia (IND) has
      traditionally been based on the finding of hyperplasia of the submucous plexus
      and increased acetylcholinesterase activity in parasympathetic nerve fibers in
      the lamina propria. However, recently it has been suggested that proposed
      diagnostic criteria relating to nerve cell density may overlap with age-related
      changes and that the finding of giant ganglia (ganglia containing more than seven
      ganglion cells) is the most relevant diagnostic parameter of IND. Ganglion cell
      counting is usually performed on conventional histological sections, whereas the
      topology of whole ganglia has been poorly studied. The aim of this study was to
      define the number of ganglion cells per ganglion and the ganglion cell density
      (the number of ganglion cells per surface area) in submucous whole-mount
      preparations of normal human colon. METHODS: Specimens from distal colon were
      obtained during postmortem examination from 14 patients who died of
      nongastrointestinal disease. The submucous layer was prepared as a whole mount
      and stained for NADPH diaphorase (a nitrergic neurotransmitter marker) and
      cuprolinic blue (a general neuronal marker). Ganglion cell density was estimated
      by counting at least 10 mm2. The number of ganglion cells per ganglion was
      counted in at least 20 ganglia per case. RESULTS: Ganglion cell density (NADPH
      diaphorase) fell markedly during the first 5 to 6 years of life (r = -0.60, P <
      .05). Most ganglion cells formed ganglia of 3 to 64 cuprolinic blue staining
      cells. The mean number of ganglion cells per ganglion did not vary with age.
      CONCLUSIONS: The density of NADPH diaphorase-positive ganglion cells in the
      submucous plexus of human distal colon decreases markedly with age. However, the
      number of ganglion cells per ganglion remains constant. These findings indicate
      that the age of the patient has crucial importance for the histolopathologic
      evaluation of enteric nervous system disorders.

PMID- 9574764
TI  - The central venous catheter as a source of medical chaos in Munchausen syndrome
      by proxy.
AB  - PURPOSE: The aim of this study was to determine what percentage of childhood
      central venous catheters (CVC) are placed in victims of Munchausen syndrome by
      proxy (MSBP) and to evaluate the clinical indications and complications of CVCs
      in MSBP. METHODS: Study design was by retrospective chart review. Data were
      obtained from the regional children's hospital and regional child abuse
      consultation network. Patients in the MSBP series were all children who on
      consultation were determined to be victims of MSBP, from 1974 through 1996.
      Patients in the central catheter series were all children who had central venous
      catheters placed 1991 through 1995, excluding children whose catheters were
      placed for cancer chemotherapy or for chronic renal failure. Consultation records
      of MSBP cases were abstracted noting the clinical characteristics of victims and
      perpetrators. Hospital procedure codes were reviewed for children who had CVCs
      placed. Those who had discharge diagnostic codes that commonly require CVC
      placement were not reviewed, but charts of children with diagnoses not usually
      requiring CVCs were evaluated. Descriptive statistics and chi2 and Fisher's Exact
      test were used for comparisons. RESULTS: Sixteen of ninety-three (17%) of MSBP
      victims had central lines, including two deaths caused by assault through the
      lines. Line sepsis occurred in 9 of 16 (56%) patients. Primary reasons for CVC
      were for administration of medicines that can normally be administered orally or
      subcutaneously (7) or for severe nutritional depletion (8). All but one of the
      children had symptoms of multiple organ system involvement. Siblings had
      frequently been victimized. The mean age of symptom onset was 19 months, yet the
      mean age at diagnosis was delayed until 82 months. All perpetrators were the
      mother. Fathers were usually physically or emotionally unavailable. Nearly one
      third of mothers had prior medical training and one third had themselves been
      victims of prior physical or sexual abuse. Ten of fifteen mothers previously
      exhibited Munchausen behavior themselves. Of children at our institution who had
      central venous catheter placement, 8 of 709 (1.1%) were MSBP victims.
      CONCLUSIONS: CVCs are frequently placed in MSBP victims for physiological
      problems, malnutrition, or failure to respond to normal treatments. Surgeons
      should consider requesting systematic evaluation for MSBP in patients seeking CVC
      placement for diagnoses not usually requiring CVCs lest they become unintentional
      collaborators in abuse of these children.

PMID- 9574765
TI  - Diagnosis and current management of penile agenesis.
AB  - Penile agenesis is a rare congenital anomaly in which early gender reassignment
      is recommended. In the past, multiple operations were carried out to form
      feminized external genitalia. The authors performed a definite genital
      reconstruction in a neonate using the posterior sagittal approach.
      Preoperatively, a magnetic resonance imaging (MRI) scan demonstrated erectile
      tissue, which was preserved and incorporated into the genital plasty. The
      operation included bilateral orchiectomy, urethral reconstruction, sigmoid
      vaginal replacement, and formation of the labia. The authors discuss the
      controversy around gender assessment. They emphasize the urethral hypotrophy to
      be a main challenge in this anomaly and conclude that immediate complete
      reconstruction is possible and should be performed in patients with this delicate
      condition.

PMID- 9574766
TI  - Thymic tissue manifesting as a posterior mediastinal mass in two children.
AB  - Two boys, ages 2 and 3 months, underwent a thoracotomy for suspected mediastinal
      mass. Thymic tissue was found. Ectopic thymic tissue should be included in
      differential diagnosis of a posterior mediastinal mass in children.

PMID- 9574767
TI  - Total anatomic urinary tract replacement and renal transplantation: a surgical
      strategy to correct severe genitourinary anomalies.
AB  - During renal transplantation, the donor ureter is normally anastomosed to the
      recipient bladder. However, preexisting anomalies of the lower urinary tract or
      previous surgical interventions may render the recipient bladder unusable.
      Although in such situations urine may be externalized via cutaneous ureterostomy
      or an ileal conduit, both techniques are frequently complicated by bacterial
      colonization or chronic infection. To overcome these problems, the authors have
      been treating such children via extensive, staged, bladder reconstruction
      (augmentation) before transplantation. On rare occasions, however, the absence of
      a usable bladder necessitates the creation of a complete neobladder from other
      visceral tissues. The authors present two cases in which patients underwent
      complete anatomic reconstruction of the lower urinary tract before renal
      transplantation. This approach results in the optimal environment for allograft
      function and leads to a greater rehabilitation than that achieved with urinary
      diversion.

PMID- 9574768
TI  - A case of resection under the IVC-atrial venovenous bypass of a hepatoblastoma
      after intraarterial chemotherapy.
AB  - An 11-month-old infant with a huge hepatoblastoma occupying almost the entire
      liver was admitted to the hospital. Serum alpha fetoprotein (AFP) level was
      elevated to 685,120 ng/mL. Combination chemotherapy with continuous arterial
      infusion of tetrahydropyranyl Adriamycin (THP-Adriamycin) and cisplatin based on
      the 91B1 protocol of the Japanese Study Group For Pediatric Liver Tumor (JPLT)
      was administered as the adjuvant chemotherapy. The tumor responded to three
      courses of chemotherapy and shrank in size, although venocavography showed that
      the inferior vena cava (IVC) was completely occluded below the entry of the
      hepatic veins. Right hepatic trisegmentectomy was performed with an IVC-atrial
      venovenous bypass that prevented massive bleeding. In this case, it was
      recognized that the IVC-atrial venovenous bypass was advantageous in an infant.
      The procedure is very simple and the blood flow obtained by the bypass was
      sufficient. Two weeks postoperatively, three courses of chemotherapy were
      initiated after the protocol. The patient remains well without signs of
      recurrence 39 months postoperatively, and the AFP value has remained within 10
      ng/mL.

PMID- 9574769
TI  - A case of mediastinal cystic hygroma whose only symptom was hoarseness.
AB  - Hoarseness caused by mediastinal cystic hygroma has not been reported before. The
      authors report a case of mediastinal cystic hygroma in which the patient's only
      symptom was hoarseness. A 6-year-old girl had hoarseness. Physical examination
      findings were normal except for indirect laryngoscopy, which showed unilateral
      vocal cord paralysis. The chest radiograph showed an opacification 3 cm wide in
      the left side of the superior mediastinum. Through a median sternotomy, a large
      multicystic mass was resected. During resection, left laryngeal recurrent nerve
      was seen to be intact, and its integrity was preserved. Six months later the left
      vocal cord was moving to a limited extent. A chest radiograph should be
      considered in a case of hoarseness caused by a peripheral nerve lesion to detect
      a mediastinal mass without any cervical component.

PMID- 9574770
TI  - Cushing's syndrome caused by an adrenal adenoma.
AB  - A 10-year-old boy presented with features of Cushing's syndrome. Investigations,
      including ultrasound scan and computed tomography scans, demonstrated a right
      adrenal tumor. The tumor was excised and histologically found to be an
      encapsulated adrenal adenoma. Surgical excision is the treatment of choice for
      adrenal tumors. However, because it is often difficult to differentiate benign
      from malignant lesions on histopathologic grounds, these patients need a regular
      long-term follow-up.

PMID- 9574771
TI  - Successful arterial switch operation in a low-birth-weight neonate who had
      transposition of the great arteries and advanced necrotizing enterocolitis.
AB  - A low-birth-weight (LBW; 1,940 g) girl was born at the gestational age of 36
      weeks without any perinatal insult. Transposition of the great arteries (TGA)
      with a large patent ductus arteriosus (PDA) and interatrial shunt was detected.
      Stage IIIB necrotizing enterocolitis (NEC) developed 46 hours after birth. She
      received ileostomy and drainage. Arterial switch operation was successfully
      performed at 23 days of age when her weight was 1,900 g. The enterostomy was
      successfully repaired at 104 days of age.

PMID- 9574772
TI  - Chylous ascites: a manifestation of blunt abdominal trauma in an infant.
AB  - This report presents an infant in whom a unique case of chylous ascites developed
      after blunt abdominal trauma. Unfortunately, this case was complicated by
      Pseudomonas peritonitis, likely from a distant source. Our patient was treated
      medically and had a good overall outcome.

PMID- 9574773
TI  - Isolated cavernous hemangioma of the stomach in a neonate.
AB  - This is a report of an extremely rare case of isolated cavernous hemangioma of
      the stomach found in a neonate. Hematemesis developed in a 7-day-old baby boy
      weighing 2.8 kg at birth. This was followed by melena. Endoscopic examination
      findings showed a large hemorrhagic mass on the lesser curvature of the stomach.
      During laparotomy, a large vascular tumor was identified and subtotal gastrectomy
      was carried out. On section, the tumor extended through the submucosa to the
      serosal surface. Histological diagnosis was cavernous hemangioma. The authors
      could collect only 10 cases of hemangioma of the stomach diagnosed in childhood
      from the world literature.

PMID- 9574774
TI  - Elective transplant pneumonectomy.
AB  - The use of a single lung transplant, modified with removal of the middle lobe of
      the donor right lung, has been described for a term neonate with respiratory
      distress secondary to right-sided congenital diaphragmatic hernia. The successful
      transplant allowed the patient to be successfully weaned from extracorporeal
      membrane oxygenation. Because of the early age of the patient at transplantation
      (3 weeks), it was unclear how the patient's left lung would develop, and there
      was uncertainty regarding the risk of life-time immunosuppression. By the age of
      4 years, 10 months, she was demonstrating some failure to thrive, hypertension,
      and hirsutism, obvious side effects of chronic immunosuppression. The question
      was raised as to the potential for transplant pneumonectomy. A ventilation
      perfusion scan demonstrated a decrease of right lung ventilation compared with
      the immediate postoperative period (27% versus 43%); right heart catheterization
      with balloon occlusion of the right main pulmonary artery suggested that the
      patient would tolerate right pneumonectomy. After discussion with the family, the
      patient underwent transplant pneumonectomy via a right posterolateral approach.
      Findings at the time of operation included mild to moderate adhesions as well as
      recurrence of the diaphragmatic hernia. She tolerated the procedure well and was
      discharged home on the fifth postoperative day with cessation of her
      immunosuppression. The immediate and medium-term success of this procedure
      suggests the potential for temporizing transplantation as a palliation to promote
      survival until the remaining native lung can provide sufficient ventilation.

PMID- 9574775
TI  - Median sternotomy and use of a pedicled sternocleidomastoid muscle flap in the
      management of recurrent tracheoesophageal fistula.
AB  - Recurrent tracheoesophageal fistula may complicate primary repair of congenital
      tracheoesophageal fistula. Standard treatment involves repair via a right lateral
      thoracotomy and use of adjacent soft tissues to separate the suture lines of the
      fistulous openings. The authors describe an alternative approach via a median
      sternotomy, which improves access, reduces the operating time required to
      identify the recurrent fistula, and enables the use of a pedicled
      sternocleidomastoid muscle flap to decrease the risk of refistulization.

PMID- 9574776
TI  - A case of zinc chloride ingestion.
AB  - Zinc chloride is a powerful corrosive agent. Reports of zinc chloride ingestion
      are uncommon, and there is little information about its toxicity and management.
      The authors report the clinical course of a 10-year-old girl who accidentally
      ingested an acid soldering flux solution (pH, 3.0; zinc chloride, 30% to < 60%).
      Systemic effects after the ingestion were unremarkable except for lethargy. Thus,
      chelation therapy was not considered. Severe gastric corrosion was caused by
      local caustic action. An antral stricture of the stomach approximately 3 weeks
      after the ingestion developed, and she underwent a modified Heineke-Mikulicz
      antropyloroplasty. Postoperatively, she made an uneventful recovery. On follow
      up, although she was tolerating a normal diet, results of a barium meal showed
      her stomach to be totally aperistaltic. Results of a nuclear medicine study
      showed moderately delayed gastric emptying. Careful long-term follow-up is
      necessary, because there is potential risk for malignancy in the damaged stomach.

PMID- 9574777
TI  - Laparoscopic removal of a large gastric trichobezoar.
AB  - A large trichobezoar has been traditionally removed by open surgery, which has
      entailed an upper abdominal incision. With the advent of laparoscopic surgery, it
      became feasible to retrieve a foreign body from the stomach without the necessity
      of a large skin incision in the upper abdomen. A 7-year-old girl presenting with
      abdominal pain, nausea, and appetite loss was admitted and evaluated. Results of
      an upper gastrointestinal series showed a large mass in the stomach that extended
      into the duodenum. Endoscopical removal had been tried twice under general
      anesthesia and resulted only in the retrieval of the small portion of the
      trichobezoar in the duodenum; total removal seemed impossible with endoscopic
      techniques. Laparoscopic removal was then under-taken to avoid the surgical scar
      in the upper abdomen. The trichobezoar was successfully retrieved through a
      gastrotomy and removed via a small suprapubic incision. This approach may be the
      treatment of choice for future cases of trichobezoar when surgery is indicated.

PMID- 9574778
TI  - Congenital short bowel syndrome associated with appendiceal agenesis and
      functional intestinal obstruction.
AB  - Congenital short bowel with functional intestinal obstruction and absence of
      appendix vermiformis is a very rare condition with poor prognosis. Seventeen
      cases of congenital short bowel have been reported previously in the literature.
      The etiology is unknown. In this report, a case of congenital short bowel,
      combined with functional intestinal obstruction, mal-rotation, and absence of the
      appendix vermiformis, is presented and the pathogenesis discussed.

PMID- 9574779
TI  - Laparoscopic appendicostomy for management of fecal incontinence.

PMID- 9574780
TI  - The anterior sagittal approach for high imperforate anus: a simplification of the
      Mollard approach.

PMID- 9574781
TI  - Neutralizing mechanism of a monoclonal antibody against Japanese encephalitis
      virus glycoprotein E.
AB  - The neutralization of Japanese encephalitis virus (JEV) was studied using JEV
      specific neutralizing (NT) monoclonal antibody (MAb) 503 that recognizes the
      envelope glycoprotein. Analysis using radiolabeled JEV and observations by
      confocal laser microscopy and electron microscopy indicated that the NT and
      protection activities of MAb 503 did not result from the prevention of the first
      step of JEV infection, binding of virus to the cell surface. Treatment with MAb
      503 strongly inhibited JEV-induced cell fusion and internalization of JEV into
      the cells, and resulted in enhanced release of JEV-RNA from the cells. These
      observations suggested that the NT activity of MAb 503 is involved in the later
      steps of JEV infection.

PMID- 9574782
TI  - Seasonal variation in agglutination of Plasmodium falciparum-infected
      erythrocytes.
AB  - Agglutination and rosette formation are in vitro characteristics of Plasmodium
      falciparum-infected erythrocytes, which have been associated with host protective
      immune responses and also with parasite virulence. The present study was carried
      out in an area of seasonal and unstable malaria transmission in eastern Sudan.
      Plasma samples were obtained before, during, and after the transmission season
      from a volunteer cohort of 64 individuals seven years of age and older. These
      plasmas were assayed for their ability to agglutinate cultured parasitized
      erythrocytes originally obtained from acute malaria infection samples taken from
      five of the cohort members. Our data show that the capacity of donor plasma
      samples to agglutinate parasitized cells depended largely on the time of sampling
      relative to the transmission season, at least within this epidemiologic setting.
      Thus, although less than half of the pretransmission season samples could
      agglutinate any of the five lines of cultured parasites, all post-transmission
      season samples could agglutinate at least one of the parasite lines, with 74%
      agglutinating two or more lines. This increase in the agglutination capacity of
      individual plasma samples after the transmission season occurred essentially
      regardless of whether an individual had experienced a clinical malaria attack
      during the transmission season. The study thus confirms the acquisition of
      agglutinating antibodies following episodes of clinical malaria, but also
      demonstrates that such acquisition can take place in the absence of disease,
      presumably as a consequence of subclinical infection. This is the first
      demonstration of marked seasonal fluctuations in the capacity of individuals'
      sera to agglutinate parasitized red blood cells. Possible explanations for this
      effect include a decrease in the levels of agglutinating antibodies between
      seasons, or shifts in the antigens being recognized by such antibodies from one
      transmission season to the next. Finally, we showed the existence of marked
      seasonal fluctuation in the levels of agglutinating antibodies, either because
      levels of such antibodies are not sustained between seasons or because the
      antigens recognized change from one season to the next.

PMID- 9574783
TI  - IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2):
      increasing prevalence with age and association with clinical immunity to malaria.
AB  - In a cross-sectional survey carried out in west Africa (The Gambia), where
      Plasmodium falciparum malaria is endemic with seasonal transmission, 178
      individuals 1-75 years of age were assessed for their antibody response to the
      malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to
      recombinant antigens representing full-length, repetitive, and group-specific
      domains of both allelic families of MSP2 was determined by ELISA. The IgG
      subclass profile of IgG-positive sera was assessed. Antibody prevalence was age
      dependent, reaching a peak during adolescence. In MSP2-seropositive individuals,
      there was a predominance of cytophilic antibodies (IgG1 and IgG3); IgG1
      antibodies were prevalent in children less than 10 years of age, whereas in
      adolescents and adults MSP2-specific antibodies were predominantly IgG3. In
      parallel, we conducted a longitudinal study of children (3-8 years of age) from
      the same community; sera collected before the malaria transmission season were
      tested for the presence of anti-MSP2 antibodies. The subsequent susceptibility of
      these children to clinical malaria was monitored and the association between anti
      MSP2 antibodies of different IgG subclasses and resistance to clinical malaria
      was tested. The presence of IgG3 antibodies to MSP2 serogroup A was negatively
      associated with the risk of clinical malaria whereas IgG1 antibodies to MSP2
      serogroup B were associated with an increased risk of clinical infection. Our
      data suggest that age/exposure-related acquisition of IgG3 antibodies to MSP2 may
      contribute to the development of clinically protective immunity to malaria.

PMID- 9574784
TI  - Longitudinal study of the antibody response to recombinant Entamoeba histolytica
      antigens in patients with amebic liver abscess.
AB  - Serology is a critical component in the diagnosis of amebic liver abscess.
      However, in areas endemic for amebiasis there is a high background level of
      seropositivity for amebiasis (owing to previous infection with Entamoeba
      histolytica), which may complicate the interpretation of a positive serologic
      test result. Recently, we reported that serologic tests based on recombinant E.
      histolytica antigens might offer improved diagnosis of current invasive amebiasis
      because they apparently differentiated active infection from past exposure to the
      parasite. To confirm this finding, we have performed a longitudinal study on 20
      patients with amebic liver abscess by examining their seroreactivity over time
      with recombinant versions of two major E. histolytica proteins, the serine rich
      E. histolytica protein (SREHP), and the 170-kD subunit of the galactose-specific
      adhesin. We found that more than 50% of the patients examined had become
      seronegative by one or both recombinant tests within 180 days of their diagnosis
      of amebic liver abscess. In the case of the recombinant SREHP-based tests, 12
      patients had become seronegative 90 days after presentation. In contrast, all
      patients remained seropositive by a standard conventional test, an indirect
      hemagglutination test, at more than six months after presentation. Our study
      shows that patients lose seroreactivity with the recombinant SREHP or 170-kD
      antigen-based tests more rapidly than with a conventional serologic test; this
      may make them useful for the serologic diagnosis of amebiasis in endemic areas.

PMID- 9574785
TI  - Immunodiagnosis of Fasciola hepatica infection (fascioliasis) in a human
      population in the Bolivian Altiplano using purified cathepsin L cysteine
      proteinase.
AB  - Cathepsin L1 (CL1), an immunogenic cysteine proteinase secreted by juvenile and
      adult Fasciola hepatica, was assessed for its potential as a diagnostic agent for
      the serologic detection of human fascioliasis. Using ELISAs, we compared the
      ability of liver fluke homogenates (LFH), excretory/secretory (ES) products, and
      CL1 to discriminate between seropositive (infected) and seronegative
      (noninfected) individuals within a population of 95 patients from the Bolivian
      Altiplano. A high prevalence of human fascioliasis has been reported in this
      region. The division between the seropositive and seronegative individuals was
      poorly defined when LFH was used as the antigen. A greater discrimination between
      these populations was achieved with both ES and CL1. A K-means cluster analysis
      using the combined ES and CL1 ELISA data identified a cluster of seropositive
      individuals. Cathepsin L1 detected a subset (20) of these seropositive
      individuals while ES detected all 26; however, ES detected nine additional
      individuals that were in the seronegative cluster. The ratio of the mean
      absorbance readings between seropositive and seronegative individuals was
      markedly improved by using conjugated second antibodies to IgG4, the predominant
      isotype elicited by infection. In these IgG4-ELISAs, CL1 again identified fewer
      individuals as seropositive than did ES, but improved the discrimination between
      the seropositive and seronegative individuals and thus provided a more conclusive
      diagnosis. Sera obtained from patients infected with schistosomiasis mansoni,
      cysticercosis, hydatidosis, and Chagas' disease were negative in these assays,
      which demonstrated the specificity of the IgG4-ELISA for detecting fascioliasis.
      Twenty of the 95 patients (21%) were seropositive for fascioliasis by the CL1
      IgG4-ELISA, confirming the earlier reports of the high prevalence of disease in
      this region. A standardized diagnostic test for human fascioliasis, based on an
      ELISA that detects IgG4 responses to CL1, could be available to all diagnostic
      centers if sufficient quantities of recombinant CL1 can be produced.

PMID- 9574786
TI  - Experimental pulmonary fibrosis induced by Paracoccidioides brasiliensis conidia:
      measurement of local host responses.
AB  - Pulmonary fibrosis was induced following inoculation of Paracoccidioides
      brasiliensis conidia intranasally in BALB/c mice. Fibrosis was associated with
      formation of granulomas, increase in lung hydroxyproline, and sustained increases
      in tissue tumor necrosis factor-alpha and transforming growth factor-beta. This
      study suggests a role for these cytokines in generation of pulmonary fibrosis
      associated with chronic granulomatous infectious diseases.

PMID- 9574788
TI  - Clinicoepidemiologic characteristics, prognostic factors, and survival analysis
      of patients coinfected with human immunodeficiency virus and Leishmania in an
      area of Madrid, Spain.
AB  - From 1987 to 1995, a retrospective case study was conducted at the Ramon y Cajal
      Hospital in Madrid, Spain, a public teaching hospital with 1,100 beds, to
      determine the clinicoepidemiologic characteristics, survival, and prognostic
      factors of patients with visceral leishmaniasis (VL) and human immunodeficiency
      virus (HIV) infection. The prevalence of VL in HIV+ patients compared with HIV-
      patients was studied. Epidemiologic, clinical, and parasitologic characteristics,
      as well as the effects of treatment, prognosis, and survival in 54 HIV+ patients
      (90 episodes) with VL were defined. Comparative survival studies among patients
      with and without acquired immunodeficiency syndrome (AIDS)-defining criteria and
      multivariate analysis of survival risk factors were performed. The prevalence of
      VL in patients with AIDS was much higher than in immunocompetent individuals. In
      spite of a good initial response to treatment for VL, 60.6% of the patients had
      relapsed by the end of one year. Mortality from the first episode was 18.5%, and
      24% died in the first month after diagnosis of any VL episode. The mean survival
      of the 29 patients who died was 10.27 months. Survival in patients with and
      without AIDS at the time of the first episode of VL was compared at 30 months:
      53.7% versus 20.5% (P = 0.00149). We found no significant difference (P = 0.24)
      in the survival of HIV+ patients who had died of VL without AIDS at the time of
      the first episode of VL compared with those of a control group of 413 dead
      patients with AIDS without VL. A diagnosis of AIDS at the time of the first
      episode of VL and thrombocytopenia were the only risk factors found related to
      survival. We conclude that in AIDS patients, VL is a recurrent disease that is
      highly prevalent and whose clinical course is modified by HIV.

PMID- 9574787
TI  - Intestinal parasitic infections in human immunodeficiency virus (HIV)-positive
      and HIV-negative individuals in San Pedro Sula, Honduras.
AB  - Honduras has at least five-times more human immunodeficiency virus (HIV)-infected
      individuals than any other country in Central America. The relationship between
      HIV status and the presence of intestinal parasites in this part of the world is
      unknown. This study presents the results from a prospective, comparative study
      for the presence of parasites in 52 HIV-positive and 48 HIV-negative persons in
      San Pedro Sula, Honduras. Infection with HIV was determined by microagglutination
      and confirmed by Western blot analysis. Parasites were detected in stools using
      formalin-ether concentration, and Kinyoun and trichrome staining. Age, sex, and
      clinical state of HIV infection were recorded for each study participant. Our
      results indicate that Cryptosporidium parvum and Strongyloides stercoralis, which
      are intracellular or live in the mucosa, were found exclusively in persons
      infected with HIV. In comparison, the prevalence of the extracellular parasites
      Giardia lamblia, Ascaris lumbricoides, and Trichuris trichiura was significantly
      higher (P < 0.05) in persons who were HIV-negative. Trichuris worms are in
      contact with the gut epithelium and less so with the mucosa, whereas
      Strongyloides lives within the gut mucosa. It is possible that changes in the gut
      epithelium due to HIV infection do not affect the mucosa and therefore would not
      affect Strongyloides. We conclude that infection with HIV may selectively deter
      the establishment of certain intestinal parasites. This may be due to the fact
      that HIV-induced enteropathy does not favor the establishment of extracellular
      parasites. Intracellular and mucosal dwelling organisms, however, may benefit
      from pathologic changes and reduced local immune responses induced by the virus,
      which, in turn, may lead to higher prevalence among HIV-infected individuals.

PMID- 9574789
TI  - Isoenzyme characterization of Leishmania isolated from human cases with localized
      cutaneous leishmaniasis from the State of Campeche, Yucatan Peninsula, Mexico.
AB  - Seventy-five isolates from the State of Campeche, Mexico, an area endemic for
      localized cutaneous leishmaniasis (LCL), were characterized by isoenzyme markers
      (glucose phosphate isomerase, mannose phospate isomerase, nucleoside hydrolase,
      phosphoglucomutase, 6-phosphogluconate dehydrogenase, and glucose-6-phosphate
      dehydrogenase). Seventy (93.3%) were identified as Leishmania (Leishmania)
      mexicana and 5 (6.7%) as L. (Viannia) braziliensis. This is the first report of
      authochthonus human LCL caused by L. (V.) braziliensis in the State of Campeche,
      Yucatan Peninsula, Mexico.

PMID- 9574790
TI  - Clinical recovery and limited cure in canine visceral leishmaniasis treated with
      aminosidine (paromomycin).
AB  - Three groups of three, six, and 12 dogs with parasitologically proven clinical
      visceral leishmaniasis (Leishmania chagasi infection) were treated with
      intramuscular aminosidine sulfate at doses of 20 mg/kg/day for 15 days; 80
      mg/kg/day for 20 days, and 40 mg/kg/day for 30 days, respectively. Follow-up was
      by parasitologic examination of bone marrow and skin, serology using the indirect
      immunofluorescent antibody test, and clinical examination for signs of visceral
      leishmaniasis or adverse effects of treatment. In animals treated with 20
      mg/kg/day, for 15 days, there was dramatic clinical improvement with
      disappearance of conjunctivitis, increase in appetite, weight gain, and recovery
      of normal skin condition and a healthy coat, but parasitologic relapse occurred
      between 50 and 100 days after initiation of treatment. Adverse effects were seen
      with treatment with 80 mg/kg/day for 20 days; three dogs died during or just
      after treatment, two showed temporary recovery, and one showed total clinical and
      parasitologic cure that was maintained for four years. Although adverse effects
      and relapses were seen in some dogs treated with 40 mg/kg/day for 30 days, three
      of 12 dogs showed complete parasitologic and clinical cure that was sustained for
      at least four years. Aminosidine treatment cannot be recommended as an
      alternative to the humane destruction of dogs for the control of canine visceral
      leishmaniasis because ineffective treatment may prolong carrier status or
      encourage development of drug resistance. This drug may be a therapeutic option
      if there is no danger of a dog acting as a reservoir of infection. Achievement of
      clinical recovery and limited cure with aminosidine suggests that further trials
      would be of value, possibly in combination with other anti-leishmanial drugs and
      with supportive measures to reduce adverse effects.

PMID- 9574791
TI  - Allopurinol as an additive to quinine in the treatment of acute complicated
      falciparum malaria.
AB  - The emergence of chloroquine resistance, and a world-wide scarcity of quinine,
      have resulted in a search for newer antimalarial drugs directed against
      falciparum malaria. Allopurinol causes virtually complete inhibition of purine
      biosynthesis of malaria parasites, which may prove lethal to the parasites. This
      study was designed to examine if allopurinol is additive to quinine in the
      treatment of acute falciparum malaria. Forty-seven Asian-Indian adults with acute
      complicated falciparum malaria were assigned to a treatment period of five days.
      They were randomly assigned to receive either oral allopurinol (12 mg/kg in three
      divided doses for five days) plus quinine (600 mg intravenously every 8 hr for
      two days, followed by 600 mg orally every 8 hr for three days ) (n = 24), or
      quinine alone (600 mg intravenously every 8 hr for two days, followed by 600 mg
      orally every 8 hr for three days) (n = 23). The responses were assessed by
      parasite clearance time, defervescence time, splenomegaly disappearance time, and
      cure rate. In the allopurinol-quinine (ALLQUIN)-treated group, all the durations
      were significantly shorter than those in the quinine alone (QUIN)-treated group.
      They were ALLQUIN versus QUIN (mean +/- SD = 65.33 +/- 11.47 hr versus 76.78 +/-
      18.20 hr; P = 0.0214; 57.66 +/- 13.01 hr versus 82.52 +/- 23.55 hr, P = 0.0002;
      10 +/- 1.64 days versus 14.65 +/- 2.4 days; P = 0.0002), respectively. The cure
      rate was higher in the ALLQUIN group (91.7%) than in the QUIN group (87%).
      However, this difference was not statistically significant. Therefore, this study
      indicates that allopurinol can be an additive to quinine to bring about both
      faster eradication of Plasmodium falciparum and clinical remission than with
      quinine alone.

PMID- 9574792
TI  - Short- and long-term action of multiple doses of ivermectin on loiasis
      microfilaremia.
AB  - One hundred nine Gabonese patients infected with Loa loa microfilariae were
      treated with ivermectin (200 microg/kg of body weight) at the Parasitology,
      Mycology and Tropical Medicine Department (Faculte de Medecine et des Sciences de
      la Sante, Libreville, Gabon). Each was given one dose per month for six
      consecutive months. The peripheral blood microfilaria (mf) count before and after
      each dose showed an average decrease in the microfilaremia of 87.3% (short-term
      single dose). An annual single-dose mass treatment with 200 microg/kg of
      ivermectin was sufficient to control the parasite in populations with low (<
      400/ml) L. loa mf counts. One month after the sixth dose (short-term-multiple
      doses), the average microfilaremia rate had decreased by 99.2% compared with the
      initial infection (35 patients). Samples were taken from 28 patients one month
      after the first dose and one month after the sixth dose. The average mf count
      decreased by 96.4% after the first dose and by 99.6% after the sixth dose
      (average residual mf counts = 13.7 and 1.5 mf/ml, respectively). The mf count
      after the sixth dose was only 11.2% of the count after the first dose. The low mf
      count persisted for more than six months after the sixth treatment (long-term
      multiple doses). Thus, mass treatment with multiple doses is more appropriate for
      areas where the blood mf count is very high. These results show that the number
      of the annual treatments used in mass chemotherapy with ivermectin can be adapted
      to each population to provide efficient protection.

PMID- 9574793
TI  - Three probable cases of Loa loa encephalopathy following ivermectin treatment for
      onchocerciasis.
AB  - Over the past nine years, more than 12 million people exposed to Onchocerca
      volvulus infection have received at least one dose of ivermectin, almost all
      without serious adverse reactions. Since 1991, however, several cases with
      neurologic manifestations, including coma, have been reported after ivermectin
      treatment of persons infected with O. volvulus who also had concomitant Loa loa
      infection with very high microfilaremia (> 50,000 microfilariae/ml of blood). In
      1995, four criteria were established to define probable cases of Loa
      encephalopathy temporally related to treatment with ivermectin (PLERI). The
      present paper describes three PLERI cases recorded in Cameroon and compares them
      with two others reported previously. Disorders of consciousness began 3-4 days
      after treatment. The objective neurologic signs were variable. The conditions
      improved favorably in three patients who benefited from early hospitalization and
      good nursing; their disorders of consciousness lasted only 2-3 days; the results
      of clinical examination became normal after one month and electroencephalographic
      abnormalities disappeared after 5-7 months. Conversely, late diagnosis and delay
      in proper management in two others probably led to worsening of the condition and
      to fatal outcome related to the usual complications of coma. In addition to these
      cases, patients w with high Loa microfilaremia also developed milder neurologic
      manifestations causing functional impairment lasting for at least one week after
      treatment. Before launching mass ivermectin distribution programs to control
      onchocerciasis in central Africa, communities in which the intensity of
      concomitant L. loa microfilaremia is high need to be identified, and specific
      educational measures and monitoring strategies should be developed and applied
      before they are treated.

PMID- 9574794
TI  - Correlations between intestinal parasitosis, physical growth, and psychomotor
      development among infants and children from rural Nicaragua.
AB  - The correlations between malnutrition, parasitosis (especially helminth
      infections), and child development are complex, and studies of these
      interrelationships will allow health agencies to maximize screening and
      intervention strategies for developing countries. We examined these correlations
      in a cross-sectional program in Carazo State, Nicaragua. Nine hundred sixty-one
      children in two age strata (ages 0-24 months and ages 2-10 years) from one urban
      and three rural communities were screened for intestinal parasites (direct smear
      and ZnSO4 flotation), malnutrition, and developmental delays. Nutritional status
      was determined as weight-for-age (WFA), weight-for-height (WFH), and height-for
      age (HFA). Developmental status (normal, suspect) was determined for the four
      subtests of the Denver II Screening Test. The prevalence of malnutrition was
      14.6% (WFA), 8.4% (WFH), and 36.3% (HFA). Parasitosis was more prevalent in
      children less than 24 months of age with low HFA, whereas in older children low
      WFA was more closely associated with parasitic infections. Ascaris and Trichuris
      were more prevalent in malnourished children. On the Denver II, suspect test
      results in all four categories (language, social, gross motor, and fine motor)
      were associated with low WFA, and suspect language tests were associated with
      both intestinal parasites (P = 0.0003) and Ascaris infection in particular (P =
      0.044). Developmental disabilities are a significant and frequently undetected
      health problem in developing countries, and malnutrition associated with
      intestinal helminth infections may be an important contributory factor for these
      disabilities.

PMID- 9574796
TI  - Genetic control of blood infection levels in human malaria: evidence for a
      complex genetic model.
AB  - There is now accumulating evidence for the involvement of genetic factors in the
      control of immune response against malaria. These arguments come from numerous
      animal models, from population studies showing associations of red blood cell
      genetic defects as well as HLA antigens with severe malaria, and from familial
      studies including a recent segregation analysis, which led to detection of a
      major gene effect predisposing to high infection levels. The heterogeneity and
      complexity of this genetic control is one of the main findings of these previous
      studies, and probably a major cause of the difficulty in developing an effective
      malaria vaccine. A segregation analysis of blood infection levels is performed
      here in 44 pedigrees living in the tropical rain forest of southern Cameroon and
      exposed to high vectorial transmission intensity. The results confirm the
      existence of complex genetic factors controlling blood infection levels in human
      malaria but are not consistent with the parent-offspring transmission of a single
      Mendelian gene. This study also shows the dramatic effect of age on infection
      levels and its interaction with a putative major gene suggesting that genetic
      related differences are much more important in children than in adults. Further
      genetic studies focused on children may help to identify the nature of the
      genetic factors involved in the expression of human malaria, by means of linkage
      analyses using both familial information and genetic markers.

PMID- 9574795
TI  - Effect of low-level pathogenic helminth infection on energy metabolism in Gambian
      children.
AB  - The aim of the present study was to determine whether an increase in resting
      energy expenditure (REE) contributes to the impaired nutritional status of
      Gambian children infected by a low level of infection with pathogenic helminths.
      The REE of 24 children infected with hookworm, Ascaris, Strongyloides, or
      Trichuris (mean +/- SEM age = 11.9 +/- 0.1 years) and eight controls without
      infection (mean +/- SEM age = 11.8 +/- 0.1 years) were measured by indirect
      calorimetry with a hood system (test A). This measurement was repeated after
      treatment with 400 mg of albendazole (patients) or a placebo (controls) (test B).
      When normalized for fat free mass, REE in test A was not different in the
      patients (177 +/- 2 kJ/kg x day) and in the controls (164 +/- 7 kJ/kg x day);
      furthermore, REE did not change significantly after treatment in the patients
      (173 +/- 3 kJ/kg x day) or in the controls (160 +/- 8 kJ/kg x day). There was no
      significant difference in the respiratory quotient between patients and controls,
      nor between tests A and B. It is concluded that a low level of helminth infection
      does not affect significantly the energy metabolism of Gambian children.

PMID- 9574797
TI  - Bancroftian filariasis in Maceio, state of Alagoas, Brazil: Observations on Culex
      quinquefasciatus after blood feeding on individuals with different densities of
      microfilariae in the peripheral blood stream.
AB  - Females of laboratory-reared Culex quinquefasciatus were allowed to take blood
      meals on individuals with low (1-100 microfilariae/ml of peripheral blood),
      moderate (101-500 microfilariae/ml), and high (> 500 microfilariae/ml)
      microfilaremia. The mosquitoes ingested 1.39-3.80 microl of blood and infective
      third-stage (L3) larvae were first recorded 13-14 days after the infecting blood
      meal. The number of microfilariae ingested by mosquitoes was proportional to the
      density of microfilariae in the peripheral blood of the human subjects, but with
      a concentration factor of up to 6.5 times the expected number. Survival of
      mosquitoes was not influenced by the density of microfilariae in the peripheral
      blood of infected individuals. Infectivity indices were proportional to
      microfilaremia in human subjects. The number of L3 larvae/female (intensity of
      infection) was not influenced by individual microfilaremia. The highest vector
      efficiency and the best experimental infection index were recorded in mosquitoes
      that blood fed on individuals with moderate microfilaremia. The results are
      discussed in relation to the transmission on Bancroftian filariasis in the study
      area.

PMID- 9574798
TI  - Risk factors for trichomoniasis among women with human immunodeficiency virus
      (HIV) infection at a public clinic in Los Angeles County, California:
      implications for HIV prevention.
AB  - Persons with human immunodeficiency virus (HIV) infection who subsequently
      develop an acute sexually transmitted disease have an increased probability of
      transmitting HIV. Therefore, characterizing such persons can help direct
      prevention efforts to a group who are likely to be continuing sources of HIV
      transmission. We assessed the incidence and factors associated with
      trichomoniasis in a cohort of HIV-infected women receiving care at a public
      clinic in Los Angeles County, California from 1992 through 1995. Demographic,
      clinical, and behavioral data were available from medical records and from
      patient interviews. Trichomonas infection was the most frequently identified
      sexually transmitted disease and was found in 37 (17.4%) of 212 women
      representing a crude incidence rate of 14.1 per 100 person-years experience. The
      crude rate of trichomoniasis was highest in black women (69.0 per 100 person
      years), women with a history of trading sex for drugs or money (51.0 per 100
      person-years), those using crack or cocaine (35.5 per 100 person-years), women
      with four or more sex partners (43.0 per 100 person years), and those born in the
      United States (23.3 per 100 person-years). Among women with severe
      immunosuppression (CD4+ count < 200), 18.4% (18 of 98) were diagnosed with
      trichomoniasis. After multivariate analysis using a Cox proportional hazards
      approach, black race (adjusted rate ratio [RR] = 5.6, 95% confidence interval
      [CI] = 2.3, 13.3) continued to be strongly associated with Trichomonas infection.
      Trading sex for money or drugs (adjusted RR = 25.2, 95% CI = 4.3, 148.6) and
      single marital status (adjusted RR = 3.7, 95% CI = 1.1, 13.0) were independent
      risk factors for trichomoniasis in nonblack women but not among black women. Data
      from this study indicate that Trichomonas may be a frequently acquired infection
      in HIV-positive women. Our findings suggest that HIV-infected women who are
      black, and nonblack women who trade sex for money or drugs or are unmarried, are
      at increased risk of trichomoniasis and therefore may be more likely to transmit
      HIV infection. Local HIV prevention strategies should target such women for
      intervention efforts.

PMID- 9574799
TI  - Echinostomiasis: a common but forgotten food-borne disease.
AB  - Human echinostomiasis, endemic to southeast Asia and the Far East, is a food
      borne, intestinal, zoonotic parasitosis attributed to at least 16 species of
      digenean trematodes transmitted by snails. Two separate life cycles of
      echinostomes, human and sylvatic, efficiently operate in endemic areas. Clinical
      symptoms of echinostomiasis include abdominal pain, violent watery diarrhea, and
      anorexia. The disease occurs focally and transmission is linked to fresh or
      brackish water habitats. Infections are associated with common sociocultural
      practices of eating raw or insufficiently cooked mollusks, fish, crustaceans, and
      amphibians, promiscuous defecation, and the use of night soil (human excrement
      collected from latrines) for fertilization of fish ponds. The prevalence of
      infection ranges from 44% in the Philippines to 5% in mainland China, and from
      50% in northern Thailand to 9% in Korea. Although the patterns of other food
      borne trematodiases have changed in Asia following changes in habits, cultural
      practices, health education, industrialization, and environmental alteration,
      human echinostomiasis remains a health problem. The disease is most prevalent in
      remote rural places among low-wage earners and in women of child bearing age.
      Echinostomiasis is aggravated by socioeconomic factors such as poverty,
      malnutrition, an explosively growing free-food market, a lack of supervised food
      inspection, poor or insufficient sanitation, other helminthiases, and declining
      economic conditions. Furthermore, World Health Organization control programs
      implemented for other food-borne helminthiases and sustained in endemic areas are
      not fully successful for echinostomiasis because these parasites display
      extremely broad specificity for the second intermediate host and are capable of
      completing the life cycle without involvement of the human host.

PMID- 9574800
TI  - Isolation of Paracoccidioides brasiliensis from armadillos (Dasypus noveminctus)
      captured in an endemic area of paracoccidioidomycosis.
AB  - Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis
      (PCM), was first isolated from armadillos from the Amazonian region where the
      mycosis is uncommon. In the present study, we report on the high incidence of PCM
      infection in armadillos from a hyperendemic region of the disease. Four nine
      banded armadillos (Dasypus novemcinctus) were captured in the endemic area of
      Botucatu, Sao Paulo, Brazil, killed by manual cervical dislocation and autopsied
      under sterile conditions. Fragments of lung, spleen, liver, and mesenteric lymph
      nodes were processed for histology, cultured on Mycosel agar at 37 degrees C, and
      homogenized for inoculation into the testis and peritoneum of hamsters. The
      animals were killed from week 6 to week 20 postinoculation and fragments of
      liver, lung, spleen, testis, and lymph nodes were cultured on brain heart
      infusion agar at 37 degrees C. Paracoccidioides brasiliensis was isolated from
      three armadillos both by direct organ culture and from the liver, spleen, lung,
      and mesenteric lymph nodes of hamsters. In addition, one positive armadillo
      presented histologically proven PCM disease in a mesenteric lymph node. The three
      armadillos isolates (Pb-A1, Pb-A2, and Pb-A4) presented thermodependent
      dimorphism, urease activity, and casein assimilation, showed amplification of the
      gp43 gene, and were highly virulent in intratesticularly inoculated hamsters. The
      isolates expressed the gp43 glycoprotein, the immunodominant antigen of the
      fungus, and reacted with a pool of sera from PCM patients. Taken together, the
      present data confirm that armadillos are a natural reservoir of P. brasiliensis
      and demonstrate that the animal is a sylvan host to the fungus.

PMID- 9574801
TI  - Molecular and serologic survey of Orientia tsutsugamushi infection among field
      rodents in southern Cholla Province, Korea.
AB  - Field rodents were collected from six areas in southern Cholla Province, Korea
      from October to December 1993. Twenty-eight (24%) of the 119 Apodemus agrarius
      were seropositive (> 1:10) for Orientia tsutsugamushi by the passive
      hemagglutination assay (PHA). Of the seropositive cases, 11 specimens had
      antibody titers greater than 1:80. No seropositive specimens were found among the
      eight Crocidura lasiura collected. On the other hand, the polymerase chain
      reaction (PCR) amplified about 520 basepairs of a gene encoding the 56-kD protein
      from the genomic DNA of 12 strains of O. tsutsugamushi tested. This target DNA
      sequence was amplified from the 11 (8.7%) blood specimens of A. agrarius, and one
      of the eight C. lasiura also showed evidence of O. tsutsugamushi infection by
      PCR. Only one of the PCR-positive samples was also PHA-positive. These results
      suggest that the PCR combined with a serologic assay more accurately detects the
      degree of infection of rodents with rickettsiae-causing scrub typhus in
      epidemiologic surveys.

PMID- 9574802
TI  - Epidemic of dengue-4 virus in Yap State, Federated States of Micronesia, and
      implication of Aedes hensilli as an epidemic vector.
AB  - A dengue fever/dengue hemorrhagic fever (DF/DHF) outbreak in Yap State caused by
      dengue-4 virus was confirmed serologically and by virus isolation from serum
      samples collected on each of three island groups. Most DF/DHF cases occurred
      during a three-month period between mid-May and early August 1995. Five fatal
      cases, three of which were in children between the ages of four and 11, occurred
      between June 20 and July 26. A serosurvey conducted in late August revealed anti
      dengue IgM prevalence rates of 18% on Yap, 36% on Eauripik, and 6% on Woleai. The
      majority of residents (93-100%) on the three islands were positive for anti
      dengue IgG antibodies, indicating widespread exposure to dengue viruses. The IgG
      titers indicative of secondary antibody response were noted on Eauripik (6.5%)
      and Woleai (17%), but were rare on Yap (0.7%). Entomologic investigations
      implicated the native mosquito species, Aedes hensilli, a member of the
      Scutellaris Group of Aedes (Stegomyia), as a previously unrecognized epidemic
      vector of dengue viruses. Aedes hensilli was the most abundant and widespread
      member of Ae. (Stegomyia) in Yap State, the only species of Ae. (Stegomyia) on
      Woleai, and the only mosquito species present on Eauripik. New distribution
      records for mosquito species are reported.

PMID- 9574803
TI  - A survey of hantavirus antibody in small-mammal populations in selected United
      States National Parks.
AB  - Hantavirus activity in 39 National Parks in the eastern and central United States
      was surveyed by testing 1,815 small mammals of 38 species for antibody reactive
      to Sin Nombre virus. Antibody-positive rodents were found throughout the area
      sampled, and in most biotic communities. Antibody was detected in 7% of 647 deer
      mice (Peromyscus maniculatus), 2% of 590 white-footed mice (P. leucopus), 17% of
      12 rice rats (Oryzomys palustris), 3% of 31 cotton rats (Sigmodon hispidus), and
      33% of 18 western harvest mice (Reithrodontomys megalotis). Antibody was also
      found in three of six species of voles, and in one of 33 chipmunks (Tamias
      minimus). Prevalence among Peromyscus was highest in the northeast. Although few
      cases of hantavirus pulmonary syndrome have been identified from the eastern and
      central regions, widespread infection in reservoir populations indicates that
      potential exists for human infection throughout much of the United States.

PMID- 9574804
TI  - Polycyclic aromatic hydrocarbons enhance the production of phorbol 12-myristate
      13-acetate-induced superoxide ions in human monocytes.
AB  - Monocytes, separated from peripheral blood, preincubated with a mixture of
      polycyclic aromatic hydrocarbons (PAHs) show an enhanced production of superoxide
      ions (O2-.) when the cells are stimulated with phorbol 12-myristate 13-acetate
      (PMA, direct activator of protein kinase C). When opsonized-zymosan is used as a
      stimulus (receptor-dependent stimulus), no enhanced production of O2-. is
      observed. Superoxide production increases dose dependently up to a PAH
      concentration of 5 microg/ml. Although the effect was rather small (125-145% of
      the control value), it was significant and reproducible. Similar enhancing
      activity was also observed in the production of hydrogen peroxide (H2O2)
      excluding an inhibitory effect of PAHs on the enzyme superoxide dismutase (SOD).
      Since the effect is related to the concentration of PMA and in the absence of
      stimulus, the O2-. is undetectable in both the control and in the PAHs-treated
      cells, it is concluded that the over production of O2-. is due to an increased
      activity of the NADPH oxidase.

PMID- 9574805
TI  - Involvement of macromolecule synthesis, endonuclease activation and c-fos
      expression in cisplatin-induced apoptosis of mouse proximal tubule cells.
AB  - We have previously demonstrated that cisplatin-induced nephrotoxicity is
      associated with the induction of apoptosis using mouse renal cells derived from
      the terminal proximal tubule (S3) which is the major target site of cisplatin
      induced injury. The purpose of this study was to elucidate the intracellular
      mechanisms leading to the cisplatin-induced apoptosis of S3 cells. Actinomycin D
      (an inhibitor of RNA synthesis), cycloheximide (an inhibitor of protein
      synthesis) and aurintricarboxylic acid (an endonuclease inhibitor) reduced the
      extent of DNA fragmentation, a biochemical parameter of apoptosis, in cisplatin
      treated S3 cells. Furthermore, cisplatin-induced apoptosis of S3 cells was
      accompanied by an increase in the level of c-fos mRNA expression, which is
      inhibited by pretreatment of the cells with actinomycin D, but not with
      cycloheximide or aurintricarboxylic acid. In contrast, outer medullary collecting
      duct cells treated with cisplatin exhibited morphological changes characteristic
      of apoptosis and an increase in the level of c-fos mRNA expression, but no
      increase in the extent of DNA fragmentation. In conclusion, the synthesis of
      macromolecules such as RNA and protein, endonuclease activation and c-fos
      expression appear to be involved in the intracellular pathways leading to the
      induction of apoptosis in cisplatin-treated S3 cells. In addition, the response
      to cisplatin may be different in different cells.

PMID- 9574806
TI  - Serum-borne factor(s) of 1,1-dichloroethylene and 1,2-dichlorobenzene-treated
      mice inhibited in vitro antibody forming cell response and natural killer cell
      activity.
AB  - 1,1-Dichloroethylene and 1,2-dichlorobenzene administered to mice produced liver
      and/or kidney damage which was quantified in this study by a histochemical
      method. The in vitro effect of sera obtained from these mice on antibody forming
      cell (AFC) response and natural killer (NK) cell activity was investigated in
      parallel with the assessment of sera tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) levels. 1,1-Dichloroethylene (100, 150 and 200 mg/kg)
      provoked liver and kidney damage. Peak kidney damage occurred 16 h after the dose
      was administered and at 24 h in the case of the liver. During the peak level of
      liver damage, a serum-borne immunosuppressive effect was also at its highest
      level. With respect to sera cytokine levels, an increase of TNF-alpha and IL-6
      was detected earlier, i.e. 6 h after toxic administration, followed by a decrease
      that tended toward a baseline level. There was a relationship between the tissue
      damage induced by 1,1-dichloroethylene and the immunosuppressive effect of mice
      sera on AFC response and NK cell activity. 1,2-Dichlorobenzene (300, 500 and 600
      mg/kg) provoked only liver damage. Peak liver damage severity was observed 48 h
      after toxic administration, whereas the highest serum-borne immunosuppressive
      effect was observed almost immediately, i.e. 6 h after administration. As regards
      sera cytokine levels, only TNF-alpha could be detected 6 h after administering
      500 and 600 mg/kg doses of 1,2 dichlorobenzene. There was a relationship between
      the liver damage induced by 1,2-dichlorobenzene and the immunosuppressive effect
      of mice sera on the AFC response. In view of the above results, this study
      suggests that the immunosuppressive effect in sera of mice treated with 1,1
      dichloroethylene and 1,2-dichlorobenzene may result from tissue damage, and that
      the increased levels of TNF-alpha and IL-6 in sera may contribute to this effect.
      Further studies are needed to clarify the factor(s) responsible, including
      transforming growth factor-beta1 (TGF-beta1) causing immunosuppression.

PMID- 9574807
TI  - Acute oral gallium arsenide exposure and changes in certain hematological,
      hepatic, renal and immunological indices at different time intervals in male
      Wistar rats.
AB  - Male albino rats were given a single oral dose of gallium arsenide (GaAs) (100,
      200 or 500 mg/kg). Erythrocyte delta-aminolevulinic acid dehydratase (ALAD)
      activity was inhibited in all the three GaAs-exposed groups accompanied by
      elevated urinary excretion of ALA. A significant increase in serum aspartate
      aminotransferase (AST) activity, and gamma-glutamyltranspeptidase (gamma-GT) was
      observed. A significant increase in hepatic malondialdehyde (MDA) and a decrease
      in hepatic glutathione contents were also noted. Renal alkaline phosphatase
      activity, urinary ALA and protein excretion increased significantly on GaAs
      exposure. These changes were accompanied by significant alterations in almost all
      the immunological variables, with an increase in gallium and arsenic
      concentration in blood and soft tissues. While most of the above biochemical
      alterations were prominent at day 7 following single exposure to 200 and 500
      mg/kg GaAs, most of the immunological indices altered with all the three doses
      and remained high even at day 21. The results suggest only a moderate effect of
      GaAs on renal and hepatic tissues. By contrast, immunological and haematological
      systems are the most vulnerable to the toxic effects of GaAs.

PMID- 9574808
TI  - Ethylmorphine N-demethylase activity as a marker for cytochrome P450 CYP3A
      activity in rat hepatic microsomes.
AB  - The purpose of this study was to evaluate the selectivity and sensitivity of
      ethylmorphine N-demethylase (EMD) as an indicator of chemically-induced
      cytochrome P450 CYP3A activity in liver microsomes of rats following treatment
      with selective enzyme inducers. Male and female Sprague-Dawley (CD) rats were
      dosed with either pregnenolone-16alpha-carbonitrile (PCN; 50 mg/kg per day for 5
      days), phenobarbital (PB; 100 mg/kg per day for 4 days), beta-naphthoflavone
      (betaNF; 100 mg/kg per day for 3 days), clofibrate (CF; 300 mg/kg per day for 14
      days), isoniazid (ISO; 100 mg/kg per day for 3 days), or dexamethasone (DEX; 50
      mg/kg per day for 4 days). Microsomes were isolated, frozen and subsequently
      assayed for protein, cytochrome P450 content and EMD activity. In males,
      significant elevations (P < 0.01) in EMD activity were observed in microsomes
      from PB-, DEX- and PCN-dosed animals compared with untreated controls. Microsomes
      from ISO- and betaNF-dosed males showed a reduction (P < 0.05) in EMD activity
      when compared with control microsomes, and CF was without effect. In females, EMD
      activities were significantly increased in microsomes from PCN, DEX and PB-dosed
      but not betaNF, ISO, or CF-dosed animals. As expected on the basis of sex-related
      differences in gene expression, EMD activities in untreated animals were
      considerably higher in males than females, attributable to constitutive CYP3A and
      CYP2C11 activities. The selectivity of EMD for induced CYP3A was confirmed on the
      basis of inhibition studies with selected steroid substrates of CYP3A, polyclonal
      anti-CYP3A1 antibodies and triacetyloleandomycin (TAO), a selective inhibitor of
      CYP3A. In conclusion, for both sexes, the greatest elevations (approximately 3-13
      fold) in EMD activity were observed in microsomes from rats dosed with DEX, a
      potent archetypal inducer with lesser but significant increases noted for PCN and
      PB, indicating that EMD is a reliable indicator of induced rat hepatic cytochrome
      P450 CYP3A activity.

PMID- 9574809
TI  - Stereochemical aspects of styrene biotransformation.
AB  - Urine of rats dosed with styrene (240 mg/kg), R-, S- and racemic styrene oxide
      (150 mg/kg) was analysed for mandelic acid enantiomers and for regioisomers and
      diastereomers of mercapturic acids by NMR spectrometry. Enantiomers of mandelic
      acid were converted to diastereomeric Mosher's derivatives prior to analysis. R-
      and S-styrene oxide yielded predominantly R- and S-mandelic acid, respectively,
      racemic styrene oxide gave predominantly the R-enantiomer whereas styrene yielded
      almost racemic mandelate. The regioselectivity of mercapturic acid formation was
      very similar for styrene, R- and S-styrene oxide. These three species yielded a
      2:1 mixture of N-acetyl-S-(1-phenyl-2-hydroxyethyl)cysteine (MA1) and N-acetyl-S
      (2-phenyl-2-hydroxyethyl)cysteine (MA2). R-Styrene oxide gave higher conversion
      to mercapturic acids (28%) than the S-isomer (19% of the dose). However, R
      styrene oxide yielded stereospecifically S,R-MA1 and R,R-MA2 whereas S-styrene
      oxide gave R,R-MA1 and S,R-MA2. Styrene yielded a mixture of diastereomeric
      mercapturic acids. The ratios of R,R-/S,R-isomers were 80:20 and 15:85 for MA1
      and MA2, respectively. These data suggest that styrene is metabolised
      stereoselectively to S-styrene oxide as a major enantiomer in rat in vivo. This
      enantiomer has been reported to be less mutagenic than R-styrene oxide in vitro.

PMID- 9574810
TI  - Ethanolamine stimulates repair processes in acute CCl4 damage of mouse liver.
AB  - Ethanolamine, a positively charged hydrophilic component of the
      phosphatidylethanolamine (PE) which is also a precursor of phosphatidylcholine
      (PC), enhances the repair processes 24 h after carbon tetrachloride (CCl4)
      intoxication of mouse liver. Ethanolamine quickly reduced aminotransferase
      activity released in the serum, increased the hepatocellular nuclear BrdU uptake,
      a marker of S phase, and the epidermal growth factor (EGF) receptor content in
      the liver injured with CCl4. Thus, exogenous administration of ethanolamine may
      function as a liver proliferating factor in CCl4 intoxicated mouse liver.

PMID- 9574811
TI  - S-(1,2-dichlorovinyl)-L-cysteine-induced dedifferentiation and p53 gene mutations
      in LLC-PK1 cells: a comparative investigation with S-(2-chloroethyl)cysteine,
      potassium bromate, cis-platinum and styrene oxide.
AB  - Exposure of cultured renal (LLC-PK1) cells for 7 weeks to non-cytotoxic
      concentrations of S-(1,2-dichlorovinyl)-L-cysteine had resulted in the induction
      of morphologically and biochemically dedifferentiated clones, which retained
      their altered properties after removal of the chemical. In this study we
      investigated by polymerase chain reaction-single strand conformational
      polymorphism (PCR-SSCP) analysis and direct sequencing if S-(1,2-dichlorovinyl)-L
      cysteine-induced LLC-PK1 clones display mutations in the p53 gene in comparison
      with wild-type clones. In addition, the characteristics of S-(1,2-dichlorovinyl)
      L-cysteine-induced clones were compared with clones induced by
      carcinogens/metabolites of carcinogens with different mechanisms of action: (i)
      The potent alkylating agent and bacterial mutagen chloroethylcysteine, the key
      metabolite of the carcinogen dichloroethane; (ii) potassium bromate, a
      nephrocarcinogen inducing reactive oxygen species, which give rise to the
      formation of 8OHdG and DNA strand-breaks; (iii) cis-platinum, a bifunctional
      cross-linking agent and strand-break inducer and (iv) styrene oxide, the main
      intermediate metabolite of styrene, an epoxide whose carcinogenicity is thought
      to be based on cytotoxicity. Three essential markers of the physiological
      integrity and renal tubule origin of the wild-type LLC-PK1 cells were disrupted
      in all chemical-derived clones: (i) the polarisation of the plasma membrane into
      a luminal and basolateral part; (ii) the sodium-dependent glucose uptake and
      (iii) the pH-dependent ammonia production. Compared with the wild-type clones,
      poly(ADP-ribosyl)ation, a posttranslational modification of nuclear proteins, was
      clearly increased in clones induced by S-(1,2-dichlorovinyl)-L-cysteine,
      potassium bromate and cis-platinum. These clones displayed also band shifts of
      p53 exon 7, indicating mutations, which were confirmed by sequencing: a double
      mutation consisting of a base substitution followed by one base insertion in the
      case of S-(1,2-dichlorovinyl)-L-cysteine and potassium bromate and a base
      substitution in the case of cis-platinum. The base insertions both lead to the
      formation of the stop codon UGA resulting in loss of protein function.

PMID- 9574812
TI  - Investigation of the potential interaction between terfenadine and tedisamil in
      human liver microsomes.
AB  - 1. The potential drug-drug interaction of terfenadine and tedisamil has been
      investigated. Terfenadine is a widely used antihistamine drug with the potential
      for QTC prolongation. Tedisamil is a potassium channel blocking agent known to
      produce bradycardia and prolong the effective refractory period in man. 2.
      Tedisamil and terfenadine were incubated with human liver microsomes for 30 min
      at 37 degrees C. No significant inhibition of terfenadine biotransformation was
      seen with 0.1 or 10 microM tedisamil as the formation of the terfenadine alcohol
      and acid metabolites were unaffected. 3. Based on the in vitro results it is
      suggested that tedisamil will not interact pharmacokinetically with terfenadine
      as it does not impair metabolism of terfenadine.

PMID- 9574813
TI  - A rapid and simple method for cryopreservation of human liver slices.
AB  - 1. Precision-cut liver slices represent a suitable and convenient in vitro
      preparation for studying metabolism and toxicity mechanisms of drugs and toxic
      chemicals. Particularly in the case of human liver slices, cryopreservation would
      enable more efficient utilization of this scarce and irregularly available
      tissue. 2. Liver slices from consecutive human livers were cryopreserved using a
      method previously developed for rat and monkey liver slices. This procedure
      involves incubation in 12% dimethyl sulphoxide for 30 min on ice and direct
      immersion into liquid nitrogen. 3. Functional integrity of cryopreserved human
      liver slices, as compared with that of fresh liver slices, was maintained at 66
      +/- 8% (alanine aminotransferase activity retained in the slices), 78 +/- 7%
      (urea synthesis), 88 +/- 14% (testosterone hydroxylation), 84 +/- 7% (N
      deethylation of lidocaine) and 88 +/- 10% (total O-deethylation of 7
      ethoxycoumarin). The ratios of testosterone metabolites did not change on
      cryopreservation. 4. These results show that the cryopreserved human liver slices
      retained the measured drug metabolism activities. Therefore, this
      cryopreservation method is suitable for storing liver slices to be used for
      comparing drug metabolism patterns, at least qualitatively, between species.

PMID- 9574815
TI  - Species differences and mechanism of the epimerization of a new MAO-A inhibitor.
AB  - 1. (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-metho xymethyl-2
      oxazolidinone (E2011) has two chiral centers in its structure. In vivo optical
      inversion of the hydroxy group at one of the chiral centers converts E2011 to a
      diastereoisomer (ER-20593). Pharmacokinetic parameters of E2011 and ER-20593 were
      determined after administration of E2011 to rat at 10 mg/kg, and the plasma
      concentration ratios of E2011 to ER-20593 were almost constant after Tmax of the
      plasma concentrations. 2. E2011 and ER-20593 were separately administered orally
      to six species in addition to rat, and the species differences in both directions
      of epimerization (i.e. from E2011 to ER-20593 and from ER-20593 to E2011) were
      studied by measuring the plasma concentrations of both compounds. In mouse,
      guinea pig, dog, and squirrel monkey, the epimerization of E2011 to ER-20593 did
      not occur, but the epimerization of ER-20593 to E2011 did. In rat, pig and rhesus
      monkey, the inversion of E2011 to ER-20593 occurred, but the ratios of this
      inversion were smaller than those for the inversion in the opposite direction.
      E2011 underwent about 15% inversion to ER-20593 in rat, which was the largest
      inversion in the seven species examined. 3. To study the mechanism of the
      epimerization, deuterium-labelled E2011 and ER-20593 (created by substituting the
      proton at the chiral center of the parent compounds for deuterium) were orally
      administered (separately) to rat and dog, and the concentration ratios and
      molecular weights of E2011 and ER-20593 in the plasma were determined by hplc and
      FAB(+)-mass spectrometry respectively. The results indicated that the major
      mechanism of the epimerization was oxidation to the carbonyl form followed by
      reduction to the original epimer and/or the other epimer. 4. The carbonyl form of
      E2011 (CO-E2011) was reduced to E2011 and ER-20593 (alcohol forms) by liver
      cytosol and microsomes from rat and dog in vitro with NADH or NADPH. The
      resultant epimeric ratios (E2011:ER-20593) were consistent with the in vivo
      results in rat and dog. 5. In conclusion, species differences in the
      epimerization of E2011 would result from product stereoselectivity of the
      reductase activity with the carbonyl intermediate.

PMID- 9574814
TI  - Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19:
      rationalization of substrate specificity and site-directed mutagenesis
      experiments in the CYP2C subfamily.
AB  - 1. The results of molecular modelling of human CYP2C isozymes, CYP2C9 and
      CYP2C19, are reported based on an alignment with a bacterial form of the enzyme,
      CYP102. 2. The three-dimensional structures of the CYP2C enzymes are consistent
      with known experimental evidence from site-directed mutagenesis, antibody
      recognition and regiospecificity of substrate metabolism. 3. The variations in
      substrate specificity between CYP2C9 and CYP2C19 can be rationalized in terms of
      single amino acid residue changes within the putative active site region, of
      which I99H appears to be the most significant.

PMID- 9574816
TI  - Identification of novel metabolites of vinorelbine in rat.
AB  - 1. Vinorelbine produced a dominant metabolite (M1) after incubation with rat
      liver microsomes. 2. Several major metabolites other than M1 were identified by
      HPLC in bile and faeces of rat after intravenous administration. 3. The
      structures of the major metabolites were identified as 15,16-epoxyvinorelbine
      (M1), 11'-hydroxyvinorelbine (M2), 19'-hydroxyvinorelbine (M3a), 15,16-epoxy-10'
      hydroxyvinorelbine (M3b) and 10'-hydroxyvinorelbine (M4) by comparison of HPLC
      retention times and by extensive analyses of two-dimensional NMR and hybrid MS/MS
      spectra.

PMID- 9574817
TI  - Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active
      drugs and non-steroidal anti-inflammatory agents.
AB  - 1. The capacity of a number of antifungal azoles, CNS-active drugs
      (anticonvulsants, antidepressants, antipsychotics and benzodiazepine
      hypnosedative-anxiolytics) and nonsteroidal anti-inflammatory agents (NSAIDs) to
      inhibit human liver microsomal 4-nitrophenol (4NP) hydroxylation, a marker of
      CYP2E1 activity, was investigated. 2. The imidazoles bifonazole, clotrimazole,
      econazole and miconazole were un- or non-competitive inhibitors of 4NP
      hydroxylation, with apparent Ki values ranging from 4 to 25 microM. Fluonazole,
      itraconazole and ketoconazole caused minor or negligible inhibition. 3. Of the
      CNS-active drugs screened, significant inhibition occurred only with tricyclic
      antidepressants, phenothiazine antipsychotics and two benzodiazepines (flurazepam
      and medazepam). Un- or non-competitive inhibition was similarly observed for the
      tricyclic antidepressants, phenothiazines, flurazepam and medazepam, with
      apparent Ki values ranging from 175 to 1000 microM. 4. Diclofenac and flufenamic
      acid were the only NSAIDs found to inhibit 4NP hydroxylation substantially;
      kinetic analysis was suggestive of activation-inhibition phenomena. 5. These data
      indicate that, although not substrates for CYP2E1, some clinically used drugs
      have the capacity to inhibit this enzyme and hence have the potential to modulate
      the toxicity of non-drug xenobiotics metabolized by CYP2E1.

PMID- 9574818
TI  - Pituitary component of the aromatic hydrocarbon-mediated expression of CYP2B and
      CYP2C11.
AB  - 1. The aim was to determine if the ethylbenzene (EB)-mediated expression of CYP2B
      and CYP2C11 involved a hormonally controlled component. 2. The hypophysectomized
      (HX) and intact rats were treated with EB for 1 or 2 days, and the effects on
      specific CYP levels measured. 3. Differences were observed in the inducibility of
      CYP2B by EB in the HX rat when compared with intact controls. Whereas significant
      elevations of CYP2B-dependent activities and protein levels were observed after
      both 1 and 2 days of EB injection in intact controls, CYP2B levels were
      significantly elevated in the HX rat only after 2 days of hydrocarbon treatment.
      4. Both CYP2C11-dependent activities and protein levels were decreased after EB
      administration to the intact rat. In contrast, CYP2C11 levels were unaffected by
      EB in the HX rat at any of the time points indicated. 5. CYP2C11 protein levels
      were unaffected by treatment with EB for 24 h in cultured hepatocytes, also
      supporting the hypothesis that hormones are involved in CYP2C11 expression. 6.
      This study indicates that pituitary input influences the EB-mediated changes in
      both CYP2B and CYP2C11. CYP2C11 is affected by EB administration in a manner
      similar to other xenobiotics such as phenobarbital. On the other hand, the
      smaller induction of CYP2B1/2 in response to EB differs from that observed with
      phenobarbital where HX augmented the response of the inducer.

PMID- 9574819
TI  - Identification of cytochrome P4503A4 as the major enzyme responsible for the
      metabolism of ivermectin by human liver microsomes.
AB  - 1. Ivermectin was extensively metabolized by human liver microsomes to at least
      10 metabolites. The structure of many of them (mostly hydroxylated and
      demethylated) was determined by 1H-NMR and LC/MS. 2. To determine which human
      cytochrome P450 isoform(s) is responsible for the metabolism of ivermectin,
      chemical inhibitors including sulphaphenazole, quinidine, furafylline,
      troleandomycin (TAO) and diethyldithiocarbamate (DDC) were used to evaluate their
      effect on ivermectin metabolism. TAO, a specific inhibitor of cytochrome P4503A4,
      was the most potent inhibitor, inhibiting the total metabolism as well as
      formation of each metabolite. Metabolism was also inhibited by an anti-human
      cytochrome 3A4 antibody by 90%. 3. When ivermectin was incubated with microsomes
      from cells expressing CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 at 4
      mg/ml protein concentrations, metabolic activity was only detected with the
      microsomes containing CYP3A4. The metabolic profile from cDNA-expressed CYP3A4
      microsomes was qualitatively similar to that from human liver microsomes. 4.
      Thus, cytochrome P4503A4 is the predominant isoform responsible for the
      metabolism of ivermectin by human liver microsomes.

PMID- 9574820
TI  - Partial hepatoprotective effects of allylthiobenzimidazole in the absence of
      cytochrome P4502E1 suppression: effects on epoxide hydrolase, rGSTA2, rGSTA3/5,
      rGSTM1 and rGSTM2 expression.
AB  - 1. 2-(Allylthio)pyrazine protects the liver against acetaminophen- and carbon
      tetrachloride-induced injury through inhibition of cytochrome P4502E1 and
      induction of glutathione S-transferases (GSTs). By comparison, the effects of
      allylthiobenzimidazole (ATB) on the levels of several hepatic cytochrome P450,
      microsomal epoxide hydrolase (mEH) and GST expression have been studied in the
      rat herein. 2. Western immunoblotting analyses revealed that ATB treatment (50
      mg/kg/day for 5 days) failed to alter cytochrome P4501A2, P4502B1/2 and P4502E1
      levels in the liver, whereas the expression of P4502C11 was reduced approximately
      50% by ATB. 3. Treatment of rat with a single dose of ATB resulted in 2-21-fold
      increases in mEH mRNA levels at 24 h with an ED50 = 60 mg/kg. mEH mRNA level was
      elevated 9- and 21-fold at 12 and 24 h after treatment at 200 mg/kg respectively
      as compared with control. Western blot analysis revealed that ATB induced mEH
      protein levels by 2-fold relative to control. 4. ATB induced the major GST mRNA
      levels as a function of dose, resulting in rGSTA2, rGSTA3/5 and rGSTM1 mRNA
      levels elevated by 20-, 6- and 8-fold at 24 h respectively. The relative rGSTM2
      mRNA level was minimally affected. Time-course studies showed that mEH, rGSTA2
      and rGSTM1 mRNA levels were significantly increased at 12 and 24 h after ATB
      treatment, returning to control levels by 48 h. Treatment of rat with ATB (20-50
      mg/kg/day for 5 days) resulted in 2-3-fold increases in mEH, rGSTA1/2, rGSTA3/5
      and rGSTM1 mRNA levels with the induction of GST subunits. 5. ATB failed to block
      carbon tetrachloride-induced liver toxicity in rat and mouse. ATB treatment (50
      mg/kg day for 3 days) prior to a lethal dose of acetaminophen significantly
      reduced acetaminophen-induced liver toxicity in mouse, as assessed by both plasma
      alanine aminotransferase activity and histopathological examination. The 30-day
      survival rate of mouse gamma-irradiated at 8 Gy failed to be improved by ATB
      pretreatment (100 mg/kg/day for 2 days). 6. These results provided evidence that
      ATB stimulated mEH and GST gene expression at early times and reduced the
      P4502C11 level in the absence of P4502E1 suppression. ATB was only partially
      effective in protecting the liver against toxicant-induced injury despite the
      presence of allylthio moiety in its chemical structure.

PMID- 9574821
TI  - The amyloid precursor protein gene: a neuropeptide gene with diverse functions in
      the central nervous system.
AB  - The amyloid precursor protein (APP) is a member of a family of proteins found in
      the central nervous system with a fundamental role in the pathogenesis of
      Alzheimer's disease. This review describes the experimental evidence that has
      provided functional insights into this protein and emphasizes the importance of
      APP in many neurobiological processes.

PMID- 9574822
TI  - The tachykinin NK1 receptor. Part I: ligands and mechanisms of cellular
      activation.
AB  - The tachykinin NK1 receptor is widely expressed in the mammalian central and
      peripheral nervous system. Powerful pharmacological tools (agonists and
      antagonists) are now available to elucidate the physiological role of NK1
      receptors at these levels, as well as to understand their role in diseases and
      establish the possible therapeutic usefulness of NK1 receptor antagonists for
      treatment of human diseases. The structure-activity studies that have led to the
      development of potent peptide and non-peptide ligands for the tachykinin NK1
      receptor are here reviewed. Among the peptide agonists and antagonists, linear
      and cyclic sequences have been developed. The non peptide antagonists belong to
      different chemical classes, i.e. steroids, perhydroisoindolones, quinuclidines,
      piperidines and tryptophane derivatives. The first non peptide antagonists for
      NK1 receptors have been obtained by random screening of chemical compounds large
      collections. The resulting leads were optimized with 'classic' structure activity
      approaches, aiming at identifying 'common' motifs for interaction with the
      receptor by ligands of different chemical classes. The results derived from the
      recent application of molecular biology techniques were useful to drive the
      design of new ligands toward a precise structural definition of ligand-receptor
      bi-molecular interactions. Studies on mutant receptors have established that the
      sites of interaction of peptide agonists and non peptide antagonists with the
      tachykinin NK1 receptor are largely non overlapping. Moreover, data obtained from
      mutagenesis of the NK1 receptor further indicate that some amino acid residues in
      the NK1 receptor sequence are critical for determining the binding affinity of
      some but not all ligands. Therefore, different antagonists discovered from random
      screening may not possess common points of interaction or common structural and
      conformational characteristics for their interaction with the tachykinin NK1
      receptor. The tachykinin NK1 receptor couples with G-proteins to determine its
      biological effects in target cells. Several G-proteins both sensitive (Go, Gi)
      and insensitive (Gq, G11) to pertussis toxin can mediate the action of NK1
      receptors. Moreover, several second messanger signalling systems (elevation of
      intracellular calcium, stimulation of phosphoinositol turnover, arachidonic acid
      mobilization, cAMP accumulation) have to be activated following NK1 receptor
      signalling. Also a direct modulation of certain ion channels at membrane level
      has been proposed. The NK1 receptor undergoes prompt and significant
      tachyphylaxis upon exposure to the agonist: this has been shown to be linked with
      receptor internalization which also occurs physiologically when the NK1 receptor
      is stimulated by endogenous tachykinins.

PMID- 9574823
TI  - Characterization of the binding of MSH-B, HB-228, GHRP-6 and 153N-6 to the human
      melanocortin receptor subtypes.
AB  - We determined the binding affinities of the MSH analogues MSH-B, HP-228 and 153N
      6 and of the enkephalin analogue GHRP-6 on a single eukaryotic cell line
      transiently expressing the human MC1, MC3, MC4 and MC5 receptors. Moreover, we
      tested the binding and cAMP response of MSH-B in comparison with alpha-MSH on
      murine B16 melanoma cells. Our results indicate that MSH-B has a potency similar
      to that of alpha-MSH and that these two peptides induce similar cAMP responses in
      murine B16 melanoma cells. HP-228 has its highest affinity for the MC1 receptor.
      For the other receptors, it has slightly higher affinity for the MC5 receptor
      than for the MC3 and MC4 receptors. 153N-6 was found to be selective for the MC1
      receptor. GHRP-6 was found to bind to the MC1 and the MC5 receptors despite its
      low structural homology with alpha-MSH. [D-Lys3]GHRP-6 bound to all the four MC
      receptors with similar affinities. The structurally related Met-enkephalin and
      the functionally related GHRH, as well as LHRH and somatostatin-14 did not bind
      to these MC receptors. The low affinity of the GH-releasing/enkephalin peptides
      may indicate that they do not interact with the MC receptors at pharmacologically
      relevant concentrations.

PMID- 9574824
TI  - Cholecystokinin B-type receptor signaling is involved in human pancreatic cancer
      cell growth.
AB  - Cholecystokinin (CCK) is known to stimulate pancreatic cancer cell growth, but no
      detailed CCK receptor subtype characterization and investigation of CCK receptor
      mediated cellular responses in human pancreatic cancer cells have been reported
      thus far. In this study, CCK binding sites were identified in human pancreatic
      cancer cells (MIA-PaCa-2) using radioligand binding studies. Pharmacological
      characterization demonstrated a single class of high-affinity CCK sites on MIA
      PaCa-2 cells (326 +/- 18 pM, receptor density 16.9 +/- 2.3 fmol/mg protein).
      These CCK binding sites displayed a typical CCKB binding profile as shown in
      competition studies by using different CCK-related compounds and non-peptide CCK
      antagonists discriminating between CCKA and CCKB sites. CCKB receptor-connected
      effector systems have been characterized in MIA-PaCA-2 cells, and their
      involvement in CCK-8S-induced proliferative effects on MIA-PaCa-2 cells has been
      demonstrated.

PMID- 9574825
TI  - Hip-Arg-Phe-, Hip-Phe-Arg- and Hip-His-Leu-cleaving dipeptidyl carboxypeptidases
      in human adrenal tumors.
AB  - Hip-Arg-Phe-, Hip-Phe-Arg- and Hip-His-Leu-cleaving dipeptidyl carboxypeptidase
      activities were measured in the supernatant (S2) and pellet (P2) fractions
      obtained by ultracentrifugation of human adrenal tumor preparations. Negligible
      enzyme activity was found in cortical tumor whereas highly significant activities
      were present in the P2 fractions of the two pheochromocytoma specimens. The
      hydrolysis rates, expressed in terms of the percent of added substrate were 58
      66%/60 min for Hip-Phe-Arg, 55-58%/60 min for Hip-Arg-Phe and 19-30%/60 min for
      Hip-His-Leu. The angiotensin-converting enzyme inhibitor, captopril,
      differentially inhibited the enzyme splitting Hip-His-Leu versus the one cleaving
      Hip-Arg-Phe; Hip-Phe-Arg is probably the substrate of both. It is concluded that
      the Hip-Arg-Phe-cleaving enzyme in adrenomedullary tumor is probably identical to
      the purportedly novel dipeptidyl carboxypeptidase that we detected earlier in
      rabbit ear artery wall, which converts (Met5)-enkephalin-Arg6,Phe7 to (Met5)
      enkephalin.

PMID- 9574826
TI  - Substance P released in the rostral brainstem of cats interacts with NK-1
      receptors during muscle pressor response.
AB  - The release of immunoreactive substance P-like substances (irSP) was measured
      from sites in the rostral brainstem (at a level 1.3 mm anterior to the obex) of
      anesthetized cats in response to fatiguing isometric contractions using SP
      antibody-coated glass microprobes. The contractions caused a pressor and
      tachycardic response. irSP were released from sites in the medial subnucleus of
      the nucleus tractus solitarius (mNTS), the solitary tract and lateral tegmental
      field at this level of the brainstem. Injections of the specific NK-1 receptor
      antagonist, GR 82334, bilaterally into the mNTS significantly reduced the muscle
      pressor response, while bilateral injections of the SP NK-1 agonist, GR 73632,
      into the mNTS significantly increased the pressor and tachycardic responses
      during the contractions. Neither the antagonist nor the agonist, at the doses
      tested, affected the resting arterial pressure or heart rate. These data indicate
      that irSP are released from sites in the mNTS during the reflex pathways
      activated by isometric contractions and that they interact with NK-1 receptors in
      the area of the mNTS to affect the cardiovascular responses during the muscle
      pressor reflex.

PMID- 9574827
TI  - Intrathecal CGRP(8-37) results in a bilateral increase in hindpaw withdrawal
      latency in rats with a unilateral thermal injury.
AB  - The present study was performed to explore the effects of intrathecal
      administration of calcitonin gene-related peptide8-37 (CGRP(8-37)) on the hindpaw
      withdrawal latency (HWL) to pressure in rats with one thermally injured hindpaw.
      Furthermore, the interaction of CGRP(8-37)and naloxone was studied. Thermal
      injury was performed by dipping the left paw into 60 degrees C for 20 s. This
      induced a significant increase in the volume of the left hindpaw (P<0.001) and
      significant bilateral decreases of the latency of hindpaw withdrawal response to
      mechanical stimulation (Left: P<0.001; right: P<0.05). Intrathecal administration
      of 10, 20 and 40 nmol of CGRP(8-37), but not of 1 or 5 nmol, induced a
      significant bilateral increase in HWLs (P<0.001). The effect of CGRP(8-37) was
      partly reversed by intrathecal injection of naloxone at a dose of 32 and 64
      microg respectively. Using radioimmunoassay, we found a significant bilateral
      increase in the concentration of CGRP-like immunoreactivity in the perfusate of
      both hindpaws 24 h after unilateral thermal injury (left: P< 0.001; right: P<
      0.05). There was also an increase in the amount of CGRP-like immunoreactivity in
      the cerebrospinal fluid (P< 0.001), but not in plasma. The results indicate that
      CGRP plays a role in the transmission of nociceptive information in the spinal
      cord of thermally injured rats. Furthermore, our findings suggest that opioids
      can modulate CGRP-related effects in the spinal cord.

PMID- 9574828
TI  - Differential modulation of mu- and delta-opioid antinociception by neuropeptide
      FF receptors in young mice.
AB  - The ability of neuropeptide FF (NPFF) to modulate mu- and delta-opioid-induced
      analgesia by intracerebroventricular administration was compared in adults and 14
      day-old mice. In adults, opioid-induced analgesia was predominantly mediated by
      mu-receptors whereas mu- and delta-receptors were equally involved in pups. An
      NPFF analog, 1 DMe, reduced the analgesic effect of DAGO and [D.Ala2]deltorphin
      I, mu and delta selective agonists respectively. However, a high dose of 1DMe (22
      nmol) increased both morphine and [D.Ala2]deltorphin-I-induced analgesia. Dose
      response curves for 1DMe in the presence of naltrindole or naltrexone, delta- and
      mu-opioid selective antagonists respectively, indicate that 1DMe preferentially
      reversed mu-receptor-mediated but increased delta-receptor-mediated analgesia.
      These findings demonstrate differences in control of mu- and delta-induced
      analgesia by NPFF receptors.

PMID- 9574829
TI  - Neurotensin stimulates CRH and ACTH release by rat adrenal medulla in vitro.
AB  - Neurotensin (NT) is a 13-amino acid peptide, widely distributed in the central
      and peripheral nervous system, which is able to stimulate the activity of the
      hypothalamo-pituitary CRH-ACTH system. We investigated by RIA the effect of NT on
      the release of CRH and ACTH immunoreactivities (ir) by rat adrenal medulla in
      vitro. NT enhanced the release of both CRH-ir and ACTH-ir, the maximal effective
      concentration being 10(-8) M. [D-Trp11]-NT, a specific NT receptor antagonist,
      abrogated the effects of NT. The stimulatory effect of 10(-8) M NT on ACTH-ir
      release was blocked by alpha-helical-CRH (an antagonist of CRH receptors),
      thereby suggesting that the enhancement in ACTH secretion is consequent to the
      stimulation of CRH release. These findings suggest that NT is a stimulator not
      only of the central (hypothalamo-pituitary), but also of the peripheral
      (intramedullary), branch of the CRH-ACTH system.

PMID- 9574830
TI  - Neuropeptide Y-like immunoreactivity in lumbar cerebrospinal fluid of patients
      after severe head trauma.
AB  - We studied head-injured patients assessed after admission to the hospital
      according to the Glasgow coma scale (3-8 points). All of them underwent surgical
      procedure after neuroradiological examination. Due to therapeutic problems, some
      of these patients had lumbar puncture on the fourth day following surgery. The
      control group consisted of patients with lumbosacral discopathy in whom lumbar
      puncture was performed during radiculography. The level of neuropeptide Y (NPY)
      was examined in 5 ml of cerebrospinal fluid (CSF). The concentration of NPY in
      CSF was assayed radioimmunologically. Taking into account our results and the
      clinical course of disease we suggest that high concentration of NPY in lumbar
      fluid in severe head-injured patients may contribute to poor clinical outcome.

PMID- 9574831
TI  - Time-dependent alterations in corticotropin-releasing factor-like
      immunoreactivity in different brain regions after acute cocaine administration to
      rats.
AB  - Recent data from various laboratories suggest that the activation of endogenous
      corticotropin-releasing factor (CRF) may contribute to the behavioral and
      neuroendocrine effects of cocaine. In the present study, the time-dependent
      variations in CRF-like immunoreactivity (CRF-LI) in the hypothalamus and several
      extrahypothalamic brain regions were determined after acute cocaine
      administration to handled rats. The intraperitoneal injection of 7.5 mg/kg
      cocaine led to a significantly decreased CRF-LI level in the basal forebrain and
      to a significantly increased CRF-LI level in the amygdala 60 min after
      administration, while the CRF-LI content was decreased in the hypothalamus and in
      the hippocampus 180 min after cocaine treatment. These results suggest that the
      durations of the effects of cocaine on CRF-LI are in the brain region-specific,
      which might contribute to the mediation of the diverse behavioral and
      neuroendocrine effects of cocaine.

PMID- 9574832
TI  - Isolation and identification of CGRP C-terminal fragments in the rat spinal cord.
AB  - In this study, we have used a liquid chromatography micropurification system in
      combination with fast atom bombardment mass spectrometry (FAB-MS) and N-terminal
      sequencing to characterize 3 calcitonin gene-related peptide (CGRP)
      immunoreactivities present in the rat spinal cord. Full-length CGRP contributed
      to approximately 68% of the total immunoreactive material, while approximately
      23% consisted of 2 C-terminal fragments, CGRP(18-37) and CGRP(19-37). Synthetic C
      terminal fragments of CGRP, e.g. CGRP(19-37), have been shown to antagonize CGRP
      effects in vitro. We show that such fragments exist in relatively substantial
      amounts in the rat spinal cord.

PMID- 9574833
TI  - Effects of single and repeated morphine administration on the prodynorphin,
      proenkephalin and dopamine D2 receptor gene expression in the mouse brain.
AB  - Effects of single (20 mg/kg i.p.) and repeated morphine administration
      (increasing doses: from 10 to 50 mg/kg i.p. twice daily for 7 days) on the
      proenkephalin (PENK), prodynorphin (PDYN) and dopamine D2 receptor (D2) mRNA
      levels in the nucleus accumbens and striatum of the mouse were investigated. As
      shown by an in situ hybridization, a single dose of morphine had no significant
      effect on the PDYN, PENK and D2 mRNA levels in the nucleus accumbens and
      striatum. Repeated treatment with morphine increased the PDYN mRNA level in both
      those structures after 2 and 72 h. In contrast to PDYN, the PENK mRNA level was
      reduced in the nucleus accumbens and remained unchanged in the striatum following
      repeated morphine administration. Repeated morphine had no effect on the D2 mRNA
      level in the nucleus accumbens and striatum after 2 h, and decreased it in the
      nucleus accumbens after 72 h only. The above results indicate that repeated
      morphine leads to long-lasting upregulation of the PDYN gene expression in the
      mouse nucleus accumbens and striatum; on the other hand, the PENK and D2 mRNA
      gene expressions are either inhibited or remain unchanged, significant changes
      being observed in the nucleus accumbens only.

PMID- 9574835
TI  - A suppressive effect of dexamethasone (DEX) on adrenocorticotropin (ACTH)
      response to vasoactive intestinal peptide (VIP) in Cushing's disease: a parallel
      modulation by DEX of ACTH responses to VIP and corticotropin-releasing hormone.
AB  - We have previously reported and confirmed that vasoactive intestinal peptide
      (VIP) is a significant stimulator of ACTH and cortisol secretion in at least some
      patients with Cushing's disease. We have also found that the hormonal responses
      to corticotropin-releasing hormone (CRH) in VIP-responsive patients with
      Cushing's disease were higher than those in VIP non-responders, which suggested a
      linkage between the actions of CRH and VIP in this disorder. Therefore, in the
      present study we examined whether this linkage also exists after glucocorticoid
      treatment by testing the effect of dexamethasone (DEX) pretreatment (1.0 mg,
      intravenous bolus, 60 min before) on ACTH and cortisol responses to CRH (100
      microg, i.v. bolus) and VIP (100 microg, i.v. bolus) in 7 patients with Cushing's
      disease who were responsive to both neuropeptides while under no DEX
      pretreatment. The results were that in 5 patients, DEX was able to significantly
      suppress the ACTH and cortisol responses to both CRH and VIP, and in the
      remaining 2 patients, DEX did not significantly affect the action of either CRH
      or VIP. This study is the first to demonstrate the parallel inhibition by DEX of
      ACTH and cortisol responses to CRH and VIP in Cushing's disease. Although the
      possibility cannot be excluded that VIP may act on CRH receptors in
      corticotropinomas as a partial agonist, it seems more likely that specific
      receptors for CRH and VIP, respectively, may concurrently express in substantial
      quantity in those corticotropinomas that are responsive to both neuropeptides.

PMID- 9574834
TI  - Stimulatory and inhibitory effects of neuropeptide Y on growth hormone secretion
      in acromegaly in vivo.
AB  - It has been reported that neuropeptide Y (NPY) affects growth hormone (GH)
      secretion in several animal species. With respect to the role of NPY in
      regulating GH release in humans, one previous study has reported that NPY
      inhibited GH secretion from cultured GH-secreting pituitary adenoma cells in
      vitro. However, since it has yet to be explored whether NPY affects GH secretion
      in acromegaly in vivo, in this study we attempted to examine the effect of
      intravenous (i.v.) bolus injection of 100 microg of human NPY on plasma GH levels
      in 15 patients with active acromegaly, trying to find a possible correlation
      among GH responses to NPY, thyrotropin-releasing hormone (TRH;500 microg, i.v.),
      luteinizing hormone-releasing hormone (LHRH;100 microg, i.v.), and bromocriptine
      (Br;2.5 mg, per os). NPY significantly increased GH secretion (more than twice
      the basal level) in 4 (27%) patients, and all of them were responsive to LHRH and
      non-responsive to Br. In contrast, 3 (20%) acromegalics showed a significant
      decrease in GH levels (less than half the baseline) after NPY, and all these
      patients were responsive to both TRH and Br. From these results, we hypothesize
      that the NPY-induced increase in GH release may be a feature of somatotroph-like
      pituitary adenoma causing acromegaly, whereas the NPY-induced decrease in GH
      secretion may be a feature of lactotroph-like adenoma.

PMID- 9574836
TI  - Effects of the CLIP fragment ACTH 20-24 on the duration of REM sleep episodes.
AB  - Substances acting upon rapid eye movement (REM) sleep or paradoxical sleep (PS)
      can affect the number and/or the duration of PS episodes. In the present study,
      we investigated the effects of the proopiomelanocortin-derived peptide CLIP
      (corticotropin-like intermediate lobe peptide, ACTH 18-39) and its N-terminal
      fragments ACTH 18-24 and ACTH 20-24 on the duration of PS episodes in rats.
      Intracerebroventricular injection of ACTH 20-24 caused a pronounced prolongation
      of PS episodes (up to 7 min duration, never seen under baseline conditions),
      whereas ACTH 18-24 acted in a similar way but without reaching statistical
      significance. We suggest that short N-terminal CLIP fragment(s) may represent
      endogenous hypnogenic factor(s) involved in the regulation of paradoxical sleep.

PMID- 9574837
TI  - Pituitary folliculo-stellate-like cell line produces a cytokine-induced
      neutrophil chemoattractant.
AB  - In previous studies, we reported that cytokine-induced neutrophil chemoattractant
      (CINC) was produced in the pituitary gland. Here we investigated the possibility
      of detection of CINC immunoreactivity in the pituitary folliculo-stellate (FS)
      like cell line (TtT/GF). Intense immunoreactivity was observed by
      immunocytochemistry in the cytoplasm and cell processes of TtT/GF cells. CINC
      immunoreactivity was detected by an enzyme-linked immunosorbent assay in as
      little as 3 h after conditioning the medium with TtT/GF cells, and it increased
      significantly in a time-dependent manner during the first 24 h of the culture.
      This immunoreactivity could be induced by lipopolysaccharide and tumor necrosis
      factor-alpha in a time- and dose-dependent manner. We also observed the
      expression of CINC mRNA in TtT/GF cells and LPS increased CINC mRNA accumulation
      in TtT/GF cells. These findings indicate that CINC produced by FS cells may play
      a role as a paracrine factor of the anterior pituitary gland, and TtT/GF will
      provide a useful model system for studying the regulation of CINC secretion by FS
      cells.

PMID- 9574838
TI  - Affinity labelling of frog brain opioid receptors by dynorphin(1-10) chloromethyl
      ketone.
AB  - It has been previously found that chloromethyl ketone derivatives of enkephalins
      bind irreversibly to the opioid receptors in vitro. Recently a novel affinity
      reagent, Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Gly chloromethyl ketone
      (Dynorphin(1-10)-Gly11 chloromethyl ketone, DynCMK) was synthesized, and its
      binding characteristics to frog (Rana esculenta) brain membranes were evaluated.
      In competition experiments, the product shows a relatively high affinity for the
      kappa-opioid binding sites labelled by [3H]ethylketocyclazocine (Ki is
      approximately equal to 200 nM), whereas its binding to the 1
      ([3H]dihydromorphine) and to the delta sites ([3H]D-Ala2-Leu5]enkephalin) is
      weaker. Preincubation of the frog brain membranes with DynCMK at micromolar
      concentrations results in a washing-resistant and dose-dependent inhibition of
      the [3H]ethylketocyclazocine binding sites. Saturation binding analysis of the
      membranes preincubated with 50 microM DynCMK reveals a significant decrease in
      the number of specific binding sites for [3H]ethylketocyclazocine compared to the
      control values. The kappa-preferring binding properties of the compound suggest
      that it could serve as an affinity label for the kappa-type of opioid receptors.

PMID- 9574839
TI  - Behavioral effects of angiotensin II microinjected into CA1 hippocampal area.
AB  - The behavioral responses of rats to bilateral microinjections of angiotensin II
      (ATII) at doses of 0.1, 0.5 and 1.0 microg into the hippocampal CA1 area of male
      Sprague-Dawley rats were studied. ATII affected locomotor activity (the number of
      horizontal and vertical movements) in a dose-related U-shaped manner. In the
      elevated plus-maze experiments, ATII at a dose of 0.1 microg microinjected
      bilaterally into the CA1 hippocampal area increased the number of entries into
      the open arms, suggesting some anxiolytic effect.

PMID- 9574841
TI  - Effect of several bicyclic peptide and cyclic pseudopeptide tachykinin NK2
      receptor antagonists in the human isolated ileum and colon.
AB  - The affinities of the monocyclic pseudopeptides MEN10,508, MEN10,573, MEN10,581,
      MEN10,612, MEN10,619 and MEN10,677, and the bicyclic peptides MEN10,627,
      MEN10,692, MEN10,771, MEN10,882 and MEN10,993 were evaluated at the tachykinin
      NK2 receptors of the human isolated ileum and colon circular muscle preparations,
      by using [betaAla8]neurokinin A(4-10) as an agonist. All of the antagonists
      tested produced a concentration-dependent and competitive antagonism of
      [betaAla8]neurokinin A(4-10)-mediated contractions in both preparations.
      MEN10,612 (pKB = 8.1) and MEN10,627 (pKB = 8.4-8.8) were among the most potent
      analogs within their chemical classes. In general, the bicyclic peptide
      antagonists were more potent than the monocyclic peptide compounds, showing a
      nanomolar affinity for the human NK2 receptor. By comparing the affinities shown
      by the antagonists under study at NK2 receptors of the human gut with the
      affinities measured at NK2 receptors of the rabbit isolated pulmonary artery and
      hamster isolated trachea, a high degree of pharmacological homology was found
      between human and rabbit NK2 receptors. The present results point out the class
      of NK2 receptor antagonists bearing a bicyclic peptide structure, like MEN10,627,
      as candidates for testing in pathological conditions characterized by exaggerated
      gut motility, in which tachykinins might play a role as non-cholinergic
      excitatory neurotransmitters.

PMID- 9574840
TI  - Involvement of tachykinin NK1 receptors in plasma protein extravasation induced
      by tachykinins in the guinea pig upper airways.
AB  - Plasma protein extravasation in the upper airways of anesthetized guinea pigs was
      measured with the FITC (Fluorescein isothiocyanate)-dextran technique. The effect
      of selective tachykinin (NK1 and NK2) receptor agonists and antagonists,
      capsaicin or antigen was studied. The tachykinin NK1 receptor agonist,
      [Sar9]substance P sulfone, induced an increase in FITC-dextran extravasation
      which was blocked by the nasal application (30-100 nmol/kg) of the tachykinin NK1
      receptor antagonist FK888, but not by 1 micromol/kg of the tachykinin NK2
      receptor antagonist, MEN10,627. The tachykinin NK2 receptor agonist,
      [betaAla8]neurokinin A-(4-10), had no effect on dye leakage. FK888 (30 nmol/kg
      intranasal) abolished the increase in the tracer recovery induced both by antigen
      and capsaicin. Conversely, the intranasal administration of MEN10,627 (0.1-1.0
      micromol/kg) significantly reduced capsaicin-induced and only marginally
      inhibited antigen-induced increase in plasma protein extravasation. Pretreatment
      with the neutral endopeptidase inhibitor, phosphoramidon, increased the effect of
      all inflammatory agents. These findings show that the plasma extravasation of the
      upper airways induced by exogenous or endogenous tachykinins is primarily
      mediated by tachykinin NK1 receptors. This inflammatory response could be
      controlled by locally applied tachykinin NK1 receptor antagonist.

PMID- 9574842
TI  - Concentration of enkephalins in cerebrospinal fluid of patients after severe head
      injury.
AB  - We studied head-injured patients treated at the Department of Neurosurgery,
      Silesian University School of Medicine, Katowice. The patients underwent lumbar
      puncture on days 1, 4 and 7 for diagnostic reasons. The levels of leu-enkephalin
      (LENK) and met-enkephalin (MENK) were examined in 4.5 ml of cerebrospinal fluid
      (CSF). The control group included patients with lumbar discopathy from whom CSF
      fluid was collected during myelography. Enkephalins were extracted by column
      chromatography and their levels were assayed radioimmunologically. The results
      indicate that enkephalins may play a certain role in the pathophysiological
      response of nervous tissue to traumatic injury. Constantly elevated MENK levels
      together with decreasing LENK levels in patients with a Glasgow coma scale score
      < or = 8 may be useful as a poor prognostic factor. It is also suggested that
      LENK and MENK play different pathophysiological roles.

PMID- 9574843
TI  - Cholecystokinin increases extracellular dopamine overflow in the anterior nucleus
      accumbens via CCK(B) receptors in the VTA assessed by in vivo voltammetry.
AB  - Differential pulse voltammetry was used to investigate the extracellular dopamine
      (DA) and DOPAC signal in the anterior part of nucleus accumbens (N.acc.) after
      microinjection of cholecystokinin (CCK) derivatives into the ventral tegmental
      area (VTA). Both the mixed CCK(A)/CCK(B) receptor agonist CCK-8s and the
      selective CCK(B) receptor agonist CCK-4 caused a dose-dependent increase in the
      DA signal after doses of 10 ng and 100 ng while CCK-8s had no effect on the DOPAC
      signal. The CCK(A) receptor antagonist L 364,718 (25 microg/kg i.p.) as well as
      the CCK(B) receptor antagonist L 365,260 (25 microg/kg i.p.) were administered
      prior to microinjection of 100 ng CCK-8s and L 365,260, but not L 364,718,
      completely inhibiting the DA increase produced by CCK-8s. Analysis of the tissue
      levels of DA and its main metabolites in the anterior part of N.acc. revealed no
      changes after CCK-8s microapplication into VTA. The presented data indicate a
      CCK(B) receptor-mediated increase in extracellular DA in the anterior N.acc.
      after microapplication of CCK derivatives into the VTA.

PMID- 9574844
TI  - In vitro exposure to peptidic delta opioid receptor antagonists results in
      limited immunosuppression.
AB  - Previous studies by our group have demonstrated that in vitro exposure to delta
      opioid receptor agonists results in a significant immunostimulation, whereas in
      vitro exposure to non-peptidic delta-opioid receptor antagonists results in
      significant suppression of various immune functions. The present study assessed
      potential immunomodulation by the peptidic delta-opioid receptor antagonists
      TIPP, D-TIPP, and ICI 174864 using a panel of in vitro immune function assays.
      Splenocytes from female B6C3F1 mice were cultured with the peptides at
      concentrations of 0.00001-10 microM. B cell proliferation was quantified
      following cellular activation, T cell function was assessed by cytokine
      production following stimulation with anti-CD3 monoclonal antibody, natural
      immunity was assessed by quantitating natural killer (NK) cell activity following
      a 24-h exposure, and macrophage function was assessed by quantification of
      interleukin-6 (IL-6) production. None of the peptides examined significantly
      affected B cell proliferation. Production of IL-2 by T cells was not consistently
      affected by exposure to either TIPP or D-TIPP, but was significantly suppressed
      at 10 microM ICI 174864. Production of IL-4, however, was significantly
      suppressed by low concentrations of either TIPP or D-TIPP, and by 10 microM ICI
      174864. IL-6 production by macrophages was unaffected except for sporadic
      incidents of enhanced production in cells exposed to ICI 174864. NK cell function
      exhibited a differential pattern of suppression, with the greatest degree of
      suppression observed following exposure to TIPP and only slight suppression in
      cells exposed to either D-TIPP or ICI 174864. These data suggest that peptidic
      delta-opioid receptor antagonists do not exhibit the same pattern or degree of
      immunosuppressive activity as the non-peptidic antagonists at equivalent in vitro
      concentrations.

PMID- 9574845
TI  - Interactions of oxytocin and vasopressin with CRF on the rat colon.
AB  - Corticotropin-releasing factor (CRF), a primary mediator of stress responses,
      produces changes in the gastrointestinal tract identical to those induced by
      stress. CRF is tenfold more potent in females than in males, but gonadectomy
      reverses this difference. We postulated that positive modulators of CRF, such as
      oxytocin (OT) and vasopressin (AVP), may act in females to potentiate effects of
      CRF and thus could account for the gender-related differences in colonic
      sensitivity to CRF and stress. Given with CRF, neither OT, peripheral AVP, nor
      central AVP increased colonic transit any more than CRF alone, suggesting that OT
      and AVP do not potentiate CRF's actions in the colon. These data indicate that
      endogenous OT and AVP do not directly affect colonic transit, and that OT and AVP
      do not account for the gender-related differences in the effects of stress and
      CRF on colonic transit.

PMID- 9574846
TI  - Differential effects of guanine nucleotides on [125I]-hCGRP(8-37) binding to
      porcine lung and human neuroblastoma cell membranes.
AB  - Calcitonin gene-related peptide (CGRP) mediates its effects by binding to
      specific receptors which are positively coupled to adenylyl cyclase. CGRP(8-37),
      a CGRP fragment devoid of the N-terminal region, was shown to be a competitive
      CGRP receptor antagonist. Only a limited amount of data exists on the usefulness
      of this ligand in studying CGRP receptors. In the present study, we used [125I]
      hCGRP(8-37) to characterize CGRP receptors in porcine lung and human
      neuroblastoma cell (SK-N-MC) membranes. [125I]-hCGRP(8-37) displayed specific and
      high affinity binding in both membrane preparations. Displacement studies using
      [125I]-hCGRP(8-37) and the agonist CGRP revealed the presence of high and low
      affinity CGRP binding sites in SK-N-MC cell and porcine lung membranes. Addition
      of guanylimidodiphosphate [Gpp(NH)p] shifted the competition curve to the right
      and changed the two affinity states of the receptor to a single affinity in SK-N
      MC cell membranes. On the other hand, in porcine lung membranes, the whole
      competition curve was shifted to the right while maintaining the two affinity
      states. Thus, our data indicate that the new radioligand [125I]-hCGRP(8-37) is a
      useful tool for characterizing CGRP receptors and their coupling to guanine
      nucleotide binding proteins.

PMID- 9574847
TI  - Patient satisfaction: ethnic origin or explanatory model?
AB  - Despite concern over their psychiatric treatment, little is known about black and
      ethnic minority patient satisfaction with psychiatric services and whether
      perceived 'ethnicity' or discrepant understanding of illness experience is most
      relevant. Twenty-one white British and 63 ethnic minority patients were
      interviewed for their opinions on psychiatric in-patient care, their treatment
      preferences and their explanatory models of their illness. The most significant
      association with satisfaction was not ethnic origin but the patient's explanatory
      model of their illness which showed little association with ethnicity whether
      patients were voluntary or involuntary. Satisfaction is most likely when there is
      concordance between the patient's and psychiatrist's explanatory model.

PMID- 9574848
TI  - Service utilisation by former long-stay psychiatric patients in Northern Ireland.
AB  - The shift from hospital to community care for people with mental health problems
      places continuing demands on community-based services. However, comparatively
      little is known about the patterns of service use among those previously resident
      in psychiatric hospitals. In this study, a total of 145 former long-stay
      psychiatric patients in Northern Ireland (NI) - most with a diagnosis of
      schizophrenia and aged under 60 - were followed up one year after discharge to
      identify the type and frequency of service use during the previous six months.
      Although a wide range of services was used, GPs, CPNs and social workers
      respectively were central to client care outside hospital. However, access to,
      and use of, services influenced, in part, by the unique integrated health and
      social services structure in NI - varied widely across types and sectors of
      accommodation. The findings have implications both for the successful management
      of community placement for former long-stay patients and for the planning and
      implementation of services for future more dependent cohorts.

PMID- 9574849
TI  - The treated prevalence of mental disorder amongst immigrants and the Australian
      born: community and primary-care rates.
AB  - The objective of the study was to explore the relationship between birthplace and
      the treated prevalence of mental disorder in Australia. Treated prevalence rates
      were derived from two surveys. These were the 1989-1990 National Health Survey,
      carried out by the Australian Bureau of Statistics, and the general practice
      component of a one-day mental health census carried out in the state of Victoria
      by the authors in 1993. Differences due to the age and sex composition of
      birthplace groups were controlled statistically. Treated rates of mental
      disorder, and the use of psychotropic medication, were consistently high amongst
      those born in Greece, and low amongst those born in the U.K./Ireland or in South
      East Asia, compared to the Australian-born. Country of birth has a significant
      effect on the treated prevalence of mental disorder, as reported by patients or
      their doctor. Further research is needed to reveal the underlying causes of these
      differences.

PMID- 9574850
TI  - Psychological distress among Ethiopian and Russian Jewish immigrants to Israel: a
      cross-cultural study.
AB  - A community survey was conducted examining the differences in levels of
      psychological distress and its symptomatology, comparing 110 Ethiopian-Jewish and
      400 Russian-Jewish immigrants to Israel. Psychological distress was measured by
      the Talbieh Brief Distress Inventory. Russian immigrants were found to be more
      distressed than their Ethiopian counterparts and this between-group difference
      can be attributed to the greater relative number of females, older immigrants and
      those with longer duration of stay in Israel in the Russian sample. The highest
      levels of distress were observed for paranoid ideation in the Ethiopian sample
      and anxiety and hostility in the Russian sample. These symptoms were independent
      of gender and time since immigration. Russians with longer duration of stay
      demonstrated higher scores signifying adjustment difficulties than their
      Ethiopian counterparts. These results suggest that the differences in levels and
      symptom expression of psychological distress are determined, to a considerable
      extent, by demographic factors (sex, age) and the differing cultural backgrounds
      of the two immigrant groups.

PMID- 9574851
TI  - A historical review of mental health services in Hong Kong (1841 to 1995).
AB  - This paper is a historical review of mental health services in Hong Kong. The
      development of mental health services in Hong Kong can be roughly divided into
      several stages: the pre-asylum period (1841-1924), the asylum period (1925-1948),
      the organization period (1 948-1965), the initial rehabilitation period (1966
      1973), the centralized rehabilitation period (1974-1981) and the civic control vs
      community care period (1982-1995). From the development of mental health services
      in Hong Kong, it is clearly demonstrated that the aims and the trends of mental
      health services had gradually progressed from a detention model, to a treatment
      model and finally to a rehabilitation model. Nevertheless, under a shortage of
      governmental resources and the severe opposition of public stigmatization,
      community based rehabilitation existed in the form of institution-like service
      units. In comparison with the international de-institutionalization and community
      care movement, mental health services in Hong Kong are not affected by any de
      institutionalization movement. Instead, the unique political and social context
      nurtured a parallel development of both institutional care and community care for
      mental patients.

PMID- 9574852
TI  - Social support and adjustment to a novel social environment.
AB  - The present article aims to examine the ways in which social support may affect
      the adaptation of individuals to a novel social environment. A distinctive
      feature of this research was the assessment of social support both before and
      after entering a completely new network of social relationships. A cohort of
      international exchange high school students (N = 242) was administered a battery
      of self-report questionnaires dealing with personality traits, perceived social
      support, coping behaviors and emotional distress before leaving Japan and six
      months after living with a host family in a foreign community. Perceived social
      support abroad contributed to less emotional distress. This health-promoting
      effect of social support was found to be mediated by adaptive coping behaviours,
      and was not due to confounding by personality traits. Perceived social support at
      home was predictive of more emotional distress abroad. Subjects who reported high
      levels of social support at home were particularly vulnerable when they entered
      the completely new environment and found that such support was no longer
      available.

PMID- 9574853
TI  - Brief report. Social self-concept of educated employed and educated unemployed
      women.

PMID- 9574854
TI  - Seasonal affective disorder among primary care consulters in January: prevalence
      and month by month consultation patterns.
AB  - BACKGROUND: Little is known about the prevalence or the consultation patterns of
      patients with seasonal affective disorder (SAD) in primary care settings.
      METHODS: Patients aged 16-64 years consulting a general practitioner (G.P.)
      during a three week period in January were screened with the Seasonal Pattern
      Assessment Questionnaire (SPAQ). Interview-confirmed cases of SAD (N = 33) were
      matched by age and sex to controls without seasonal morbidity and primary care
      consultation patterns were compared over a 5 year period. RESULTS: Of 692
      patients screened, 64 (9.3%) satisfied SPAQ criteria for winter SAD. Patients
      with SAD showed no winter excess of consultations but were high year round
      consulters, averaging 1.8 times more consultations than controls. CONCLUSIONS:
      High levels of SAD caseness on the SPAQ were found among patients consulting in
      primary care during January. Possible explanations for the high non-seasonal
      consultation patterns among SAD patients include somatisation and diagnostic
      inaccuracies. LIMITATIONS: Diagnostic criteria for SAD, and the SPAQ in
      particular, may be over-inclusive. The SPAQ completion rate (about 39% of
      eligible patients consulting a G.P.) was relatively low. CLINICAL RELEVANCE:
      Patients with SAD (using SPAQ criteria) commonly consult their G.P.s in winter
      but frequency, rather than seasonality, of consultation may be a better guide to
      diagnosing SAD in primary care.

PMID- 9574855
TI  - Positive and negative acute phase proteins in affective subtypes.
AB  - BACKGROUND: Patients with affective disorders show evidence of increased positive
      acute phase proteins (e.g., C-reactive protein [CRP], alpha-1-acid glycoprotein,
      haptoglobin) and decreased negative acute phase proteins (e.g., albumin,
      transferrin [TFN]). CRP reductions have been reported to be greater in patients
      who later respond to lithium augmentation, and these patients also demonstrate
      higher CRP levels on the failed antidepressant, prior to the addition of lithium.
      However, association of such systemic immune changes with affective subtypes,
      mood state, psychotropic medications, age and gender has not been extensively
      explored. METHODS: The present study assessed levels of CRP and TFN in 79 bipolar
      I, 24 bipolar II, and 46 unipolar depressed outpatients in comparison to 22
      healthy controls. RESULTS: Patients on lithium monotherapy were significantly
      less likely to demonstrate elevated CRP, and a similar trend was noted in those
      patients taking lithium in combination with an antidepressant. The frequency of
      elevated CRP levels did not significantly vary for different psychotropic
      medications, affective subgroups, or mood states. TFN levels were not influenced
      by diagnosis, affective state or psychotropic medications. LIMITATIONS: Due to
      the retrospective nature of this analysis, the affective subgroups were
      heterogeneous with regard to medications and affective state, and differed
      significantly in age. Due to limitations in subgroup sample size, significant
      effects of clinical variables may have been masked by interactions of
      medications, age, affective subtype, and mood state. CONCLUSIONS: The results
      imply that lithium may play a role in normalizing systemic immune activation
      associated with depression. Whether such immune changes may be restricted to
      lithium-responsive subgroups deserves further evaluation.

PMID- 9574856
TI  - Which patients receive antidepressants? A 'real world' telephone study.
AB  - INTRODUCTION: The use of antidepressants has been questioned with respect to both
      undertreatment and inadequate prescription. The present investigation was
      therefore launched to assess the psychopathology profiles of antidepressant
      users. METHODS: A representative sample was constituted on the basis of usual
      antidepressant consumption, and ICD 10 compatible diagnoses were obtained after
      telephone administration of a structured psychiatric interview. RESULTS: The most
      often used drugs were fluoxetine, followed by tricyclic antidepressants.
      Coprescription existed in slightly less than two thirds of antidepressant users.
      ICD 10 diagnoses were compared to currently available prescription guidelines.
      Fluoxetine prescription, as compared to other drugs, was found to be
      significantly more compliant with these guidelines; conversely, in 22% of
      antidepressant users, no complete ICD 10 diagnosis could be documented. These
      results are discussed in the light of report accuracy and anecdotal or
      'heterodox' indications of antidepressants. CONCLUSION: Altogether, the present
      study confirms previous doubts regarding appropriate use of antidepressants and
      stresses the need for more explicit and comprehensive clinical guidelines. It
      does not substantiate, however, any evidence for a 'recreational' use of these
      products.

PMID- 9574857
TI  - Psychiatric and polysomnographic evaluation of sleep disturbances.
AB  - BACKGROUND: We evaluated psychiatrically 100 subjects, who were referred to a
      sleep laboratory in a general hospital because of sleep complaints. METHODS: All
      subjects were interviewed using a Structured Clinical Interview for DSM-III-R and
      underwent one night of standard polysomnography (PSG) examination. RESULTS: Forty
      three percent of the population had at least one Axis I DSM-III-R disorder. High
      rate of depressive mood disorder (24%) was observed in our sample, in contrast to
      low prevalence of alcohol and drug abuse (4%). Our results of a Israeli
      population are different from the United States studies in respect to alcohol and
      drug abuse. Furthermore, 11% of patients with PSG diagnosis exhibited comorbid
      psychiatric disorder. CONCLUSION: it appears that individuals with sleep
      complaints have high rate of psychiatric morbidity, especially mood disorders.
      LIMITATION: The rapid eye movement (REM) latency, a biological marker for
      depression, was not investigated. CLINICAL RELEVANCE: it seems that both PSG and
      psychiatric evaluation of sleep disturbance are of importance for appropriate
      therapeutic strategy for individuals with sleep complaints, especially in those
      with features of suspected depressive mood disorders.

PMID- 9574858
TI  - Maintenance strategies for unipolar depression: an observational study of levels
      of treatment and recurrence.
AB  - BACKGROUND: This paper analyses data from a large observational study of the
      course of affective illness to provide insight into the duration and dose of
      effective maintenance therapies. METHODS: The data are 236 unipolar patients who
      had received antidepressants during recovery and were followed for affective
      recurrence for up to 5 years. Using data on the naturally selected somatic
      treatments, we have conducted analyses that adjust for the potential confounding
      effects of prognosis and treatment intensity to estimate the causal effect of
      level of medication on the course of recurrence. RESULTS: The results of these
      analyses show that it is important for patients to remain on the level of
      somatotherapy used to treat the acute episode for the initial 8 months after
      symptoms have abated. After that time, the rate of recurrence for patients with
      fewer than five previous episodes is approximately 1% per week or less at all
      levels of medication (including discontinuation). Patients who had experienced
      more than several recurrences are at greater risk of recurrence and continue to
      benefit from any level of medication during the first year after recovery.
      CONCLUSIONS: The CDS analyses reported here suggest that effective maintenance
      strategies for all but highly recurrent patients may be a middle road, opting for
      full-dose strategies of limited duration. These results have implications at both
      the policy and the clinical level, given the need to consider both monetary and
      nonmonetary costs (side-effects) associated with continued pharmacotherapy during
      remission. LIMITATIONS: The observational design of the CDS limits the degree to
      which cause and effect relationships can be inferred from the observed
      associations.

PMID- 9574859
TI  - Correlations between plasma-neuropeptides and temperament dimensions differ
      between suicidal patients and healthy controls.
AB  - BACKGROUND: Decreased plasma levels of plasma-neuropeptide Y (NPY) and plasma
      corticotropin releasing hormone (CRH), and increased levels of plasma delta-sleep
      inducing peptide (DSIP) in suicide attempters with mood disorders have previously
      been observed. This study was performed in order to further understand the
      clinical relevance of these findings. METHODS: Examination of correlates between
      temperament dimensions (Karolinska Scales of Personality (KSP), the Eysenck
      Personality Questionnaire together with the IVE- impulsiveness scale (EPQI), and
      the Marke-Nyman Temperament (MNT)) and NPY, CRH and DSIP and serum-cortisol in
      the dexamethasone suppression test (DST) in 38 suicidal patients and matched
      controls. RESULTS: NPY correlated significantly and positively with
      psychasthenia, irritability, and stability and significantly and negatively with
      validity in patients, but significantly and negatively with muscular tension,
      psychasthenia, verbal aggression and irritability in controls. DSIP correlated
      significantly and positively with impulsiveness (EPQI) in controls. CRH
      correlated negatively with lie in controls. Cortisol correlated significantly and
      positively with validity, extraversion and verbal aggression and significantly
      and negatively with inhibition of aggression in controls. CONCLUSION: NPY may be
      related to stress tolerance. DSIP seems to be associated with
      impulsivity/antisocial traits. LIMITATIONS: Non-suicidal patients were not
      included in the examination. CLINICAL RELEVANCE: The state of depression or
      stress seems to influence the correlations studied.

PMID- 9574860
TI  - Lack of insight in mood disorders.
AB  - BACKGROUND: The study's aim was to examine insight in mood disorders in relation
      to type of mood episode, psychotic state, and insight change over the episode.
      METHODS: Fifty four patients with a manic or major depressive episode were
      interviewed for insight assessment at admission and discharge. RESULTS: At
      admission, mania patients had more severe insight impairment that depressive
      ones, depressive patients with psychosis had poorer insight than those without
      psychosis, and mania patients had poor insight irrespective of the presence of
      psychotic symptoms. At discharge some insight impairment was observed in mania.
      CONCLUSION: Lack of insight was a prevalent condition in psychotic depression and
      mania. LIMITATIONS: A global insight measure was used. Ratings of insight were
      not blind to the ratings of other symptoms. CLINICAL RELEVANCE: Considering
      residual insight impairment in mania may be important to maximize compliance and
      to prevent relapse.

PMID- 9574861
TI  - A meta-analysis of the effects of cognitive therapy in depressed patients.
AB  - BACKGROUND: Cognitive therapy (CT) has been studied in 78 controlled clinical
      trials from 1977 to 1996. METHOD: The meta-analysis used Hedges and Olkin d+ and
      included 48 high-quality controlled trials. The 2765 patients presented non
      psychotic and non-bipolar major depression, or dysthymia of mild to moderate
      severity. RESULTS: At post-test CT appeared significantly better than waiting
      list, antidepressants (P < 0.0001) and a group of miscellaneous therapies (P <
      0.01). But, CT was equal to behaviour therapy. As between-trial homogeneity was
      not met, the comparisons of CT with waiting-list or placebo, and other therapies
      should be taken cautiously. In contrast, between-trial homogeneity was high for
      the comparisons of CT with behaviour therapy and antidepressants. A review of
      eight follow-up studies comparing CT with antidepressants suggested that CT may
      prevent relapses in the long-term, while relapse rate is high with
      antidepressants in naturalistic studies. CONCLUSION: CT is effective in patients
      with mild or moderate depression.

PMID- 9574862
TI  - A controlled study of folate levels in Chinese inpatients with major depression
      in Hong Kong.
AB  - BACKGROUND: Although Western and, in particular, British studies have revealed a
      substantial rate of hypofolatemia in patients with depression, few such studies
      have been conducted in Asian populations. METHODS: A group of 117 newly admitted
      inpatients with DSM-III-R major depression and 72 healthy controls underwent
      blood investigations and psychometric assessments. RESULTS: Patients had a
      significantly lower mean serum folate level (24.6+/-10.2 vs. 30.3+/-11.4 nmol/l,
      P < 0.001) but a higher mean erythrocyte folate level (801.8+/-284.6 nmol/l vs.
      699.5+/-248.7 nmol/l, P < 0.01) than control subjects. No patient or control
      subjects had low folate, while only four patients (3.4%) and six control subjects
      (8.3%) had low erythrocyte folate. Folate levels were not related to patients'
      age, duration of illness, Hamilton Depression Rating Scale, Beck Depression
      Inventory and Global Assessment Scale scores, and prior psychotropic drug usage.
      Both patients and control subjects revealed a high intake of green vegetables.
      CONCLUSION: Patients' lower serum folate level was likely to be secondary to
      their depression but, being well in the normal range, should not have aggravated
      their depressive symptoms. Culturally patterned health beliefs and dietary
      practices can influence the connection between folate status and depression in
      different societies. LIMITATIONS: Patients were not drug-free, while the lack of
      detailed dietary analysis and longitudinal data on folate level and psychiatric
      outcome tempered the above conclusion. CLINICAL RELEVANCE: Since normofolatemia
      is normative in Hong Kong, the routine screening of folate levels in Chinese
      depressive patients is not indicated. However, a double-blind, placebo-controlled
      trial may be useful for finding out whether Chinese patients will still benefit
      from folate pharmacotherapy.

PMID- 9574863
TI  - Use of the selective serotonin reuptake inhibitor citalopram in the treatment of
      generalized social phobia.
AB  - BACKGROUND: There is increasing evidence that social phobia responds to treatment
      with selective serotonin reuptake inhibitors (SSRIs). However, the efficacy of
      citalopram, the most selective of the SSRIs, in social phobia has not been well
      documented. METHODS: Citalopram was used on an open-label naturalistic basis in
      22 social phobia patients presenting for treatment (40 mg daily for 12 weeks).
      Patients were rated with the Liebowitz Social Anxiety Scale and the Clinical
      Global Impressions (CGI) scale. RESULTS: Ratings on the Liebowitz Social Anxiety
      Scale and the CGI were significantly improved after treatment. A total of 86% of
      patients were responders at week 12. LIMITATION: Open, uncontrolled study.
      CONCLUSIONS: Citalopram appears to be effective in the treatment of social
      phobia. A controlled trial is warranted to confirm these data. The role of
      serotonin in social phobia deserves further study.

PMID- 9574864
TI  - Responses of laryngeal capsaicin-sensitive receptors to volatile anesthetics in
      anesthetized dogs.
AB  - The responses of laryngeal capsaicin (CAPS)-sensitive receptors to halothane,
      enflurane, isoflurane and sevoflurane were evaluated in anesthetized
      spontaneously breathing dogs from the afferent activity of the internal branch of
      the superior laryngeal nerve. The CAPS-sensitive receptors were clearly
      distinguished from irritant receptors by their responsiveness to CAPS and their
      lack of responsiveness to water. All the CAPS-sensitive receptors were
      significantly stimulated by all volatile anesthetics in a concentration-related
      manner, and the activation by halothane, enflurane, and isoflurane was
      significantly greater than by sevoflurane. In contrast, responses of irritant
      receptors to the volatile anesthetics were divided into three types (stimulation,
      inhibition or non-response), and did not differ among anesthetics. In conclusion,
      the present study demonstrated that the CAPS-sensitive receptors were
      consistently stimulated by halogenated volatile anesthetics and especially by
      halothane, enflurane, and isoflurane, and that these responses were dissimilar to
      the variable responses of irritant receptors.

PMID- 9574865
TI  - A possible role for protein kinase C in CO2/H+-induced c-fos mRNA expression in
      PC12 cells.
AB  - Recently we have found that hypercapnia induces nuclear protein (FOS) expression
      in the brainstem chemosensitive neurons, including catecholamine-containing
      cells. In the present studies we examined the role of protein kinase C (PKC)
      pathway in CO2-induced c-fos expression. Because of the complexity of the CNS
      system, experiments were performed in pheochromocytoma cells (PC12 cells). These
      cells originate from neuronal crest and express catecholaminergic traits. We
      depleted PKC from PC12 cells by prolonged (48 h) exposure to high concentration
      of phorbol 12-myristate, 13-acetate (PMA, 100 nM), and then determined the
      expression of: (1) c-fos mRNA by Northern blot (2) PKC isoforms, tyrosine
      phosphorylated and unphosphorylated MAP (mitogen activated protein) kinases by
      Western blot. Depletion of PKC abolished the effect of CO2 on c-fos mRNA
      expression, inhibited MAP kinases tyrosine phosphorylation and suppressed the
      expression of PKC(alpha) and PKC(zeta). These results suggest that MAP kinases,
      PKC(alpha) and/or PKC(beta) might be involved in CO2-induced c-fos mRNA
      expression.

PMID- 9574866
TI  - CO2-sensitive neurons in organotypic cultures of the fetal rat medulla.
AB  - Medullary slices of the fetal rat at gestational day 16 were cultivated
      (organotypic culture) for up to 20 days and current clamp experiments were
      performed on outgrowing neurons. CO2-sensitivity was tested by changing the
      P(CO2) in the bath solution (equilibrating CO2 fraction from 0.02 to 0.09). Two
      groups of CO2-sensitive neurons were found; one with and the other without
      intrinsic CO2-chemosensitivity. Neurons with intrinsic CO2-sensitivity maintained
      their spontaneous activity and chemosensitivity after blockade of synaptic
      transmission. These neurons exhibited action potentials that were preceeded by a
      spontaneous interspike depolarization and followed by an afterhyperpolarization
      (beating neurons). Increasing P(CO2) either decreased (inhibited neurons, n = 55)
      or increased the spike frequency of these neurons (stimulated neurons, n = 31).
      The reduced activity of CO2-inhibited neurons was associated with membrane
      hyperpolarization and/or decreases in the slope of interspike depolarization. In
      contrast CO2-stimulated neurons were depolarized and the slope of their
      interspike depolarization was augmented during acidosis. In addition, we
      demonstrated a strong voltage dependence of CO2-induced effects on membrane
      potential and spike frequency. Neurons with non-beating activity did not show a
      spontaneous interspike depolarization and their spike generation and CO2
      sensitivity appeared to be entirely produced through synaptic inputs. The CO2
      mediated changes in electrical properties of these neurons closely resemble those
      of various CNS neurons, including respiratory neurons, in whole animal or
      neonatal brainstem-spinal cord preparations.

PMID- 9574867
TI  - Diaphragmatic activity during biphasic ventilatory response to hypoxia in rats.
AB  - To determine its role in the biphasic ventilatory response to hypoxia, we
      examined the diaphragmatic activity at its peak (DI), at the end of expiration
      (DE), and ventilation in adult anesthetized rats: (1) after 10 min of graded
      levels of poikilocapnic hypoxia (16, 14, 12, 10% O2); (2) at 1, 5 and 10 min of
      steady hypoxia (10% O2) in intact and vagotomized rats. (1) Gradual hypoxia
      progressively increased VE and DE but DI only at 10% O2; (2) 10% O2 induced an
      initial increase in ventilation followed by its consistent decline. VT, DI and DE
      at first increased, then VT and DI decreased, while DE remained augmented. VT and
      phasic activation of the diaphragm (DI - DE) decreased in parallel. Bilateral
      vagotomy did not affect the biphasic response of Ve. These results suggest that
      (1) the increased end-expiratory activity of the diaphragm limits its phasic
      inspiratory activation and thus contributes to the biphasic character of the
      ventilatory response to sustained hypoxia; (2) vagal input does not play a major
      role in this phenomenon.

PMID- 9574868
TI  - Skeletal muscle microcirculatory structure and hemodynamics in diabetes.
AB  - Within skeletal muscle, insulin-dependent (Type 1) diabetes produces straighter,
      narrower capillaries. To test the hypothesis that these microvascular alterations
      would be associated with impaired capillary hemodynamics, intravital microscopy
      techniques were used to study the in vivo spinotrapezius muscle microcirculation
      of age-matched control (C) and streptozotocin (STZ) induced diabetic (D) rats. D
      rats exhibited a marked reduction in body weight (C, 266 +/- 5 g; D, 150 +/- 6 g;
      P < 0.001). At resting sarcomere lengths (i.e. approximately 2.7 microm), the
      additional capillary length arising from tortuosity and branching was less in D
      muscle (C, 10.5 +/- 0.8%; D, 5.3 +/- 1.0%, P < 0.01). Capillary diameter was
      reduced in D muscle (C, 5.4 +/- 0.1 microm; D, 4.6 +/- 0.1 microm; P < 0.001),
      and was positively correlated (r = 0.71) with the decreased proportion of
      capillaries sustaining flow (C, 85 +/- 5%; D, 53 +/- 3%; P < 0.001). Within those
      'flowing' capillaries, red blood cell (RBC) velocity and flux were reduced 29 and
      43%, respectively in D muscle (both P < 0.05). This reduced calculated O2
      delivery by 57% per unit tissue width and 41% per unit muscle mass. Capillary
      'tube' hematocrit was unchanged from control values (C, 0.22 +/- 0.02; D, 0.22 +/
      0.02). We conclude that, in the diabetic state, microvascular remodeling is
      associated with a reduced proportion of 'flowing' capillaries and a reduction in
      RBC velocity and flux in these vessels such that skeletal muscle O2 delivery is
      markedly reduced.

PMID- 9574869
TI  - Morphometric estimate of gas-exchange tissue in the new-born tammar wallaby,
      Macropus eugenii.
AB  - The lung of the new-born marsupial is at the terminal air sac stage of
      development. The maturational status of the lung of new-born tammar wallaby was
      assessed using established morphometric techniques and the results were compared
      with data from a morphometric study of the lung of the rat. Volume densities of
      the parenchyma and non-parenchyma, conducting airways and blood vessels, the
      relative volumes of airspace and tissue, the thickness and the composition of the
      septa differed between the two species. In addition the volume of capillaries and
      the surface area of the effective gas-exchange tissue was greater in the new-born
      rat than in the new-born tammar pouch young. The lung of the new-born tammar
      appears to be at an earlier phase of the terminal air sac stage than that of the
      new-born rat. Lung development up to birth appears to be commensurate to the
      metabolic needs of the organism at birth.

PMID- 9574870
TI  - Increased fiber capillarization in flight muscle of finch at altitude.
AB  - We examined fiber capillarization and ultrastructure in the highly aerobic flight
      muscle of six gray crowned rosy finches (Leucosticte arctoa; mass 22.9 +/- 0.5
      (SE) g) living at altitude (A; White Mountains of Eastern California; 4000 m)
      compared to eight sea-level (SL) house finches (Carpodacus mexicanus, mass, 19.8
      +/- 0.6 g) of the same subfamily, Carduelinae. Capillary length per fiber volume
      (A, 10,400 +/- 409 mm(-2); SL, 7513 +/- 423; P < 0.001) and capillary-to-fiber
      ratio (A, 2.32 +/- 0.07; SL, 1.85 +/- 0.06; P < 0.001) were significantly greater
      in A, with no difference in fiber cross-sectional area compared to SL. Capillary
      geometry was significantly different in A, yielding a greater contribution of
      tortuosity and branching to capillary length than in SL. Capillary-to-fiber
      surface ratio and fiber mitochondrial volume were both greater in A, but their
      ratio was similar to SL, indicating a proportional increase in the size of the
      capillary to fiber interface and fiber mitochondrial volume in A to sustain high
      levels of aerobic capacity while living at altitude.

PMID- 9574871
TI  - Vascular remodeling and growth factor gene expression in the rat lung during
      hypoxia.
AB  - Recent studies suggest that the vasoactive peptides endothelin-1 and -3 and the
      mitogens VEGF and PDGF-A and -B could be involved in the pathogenesis of hypoxic
      pulmonary hypertension. We were interested to investigate whether these peptides
      could also be involved in the vascular remodeling occurring during chronic
      hypoxia (10% oxygen; 1 and 3 weeks) in the rat. Hypoxia increased significantly
      systolic right ventricular pressure and typical morphological signs of vascular
      remodeling were found. This was accompanied by increased ET-1 and the ET-3 mRNA
      expression after acute (6 h; P < 0.05) and chronic hypoxia of 1 (P < 0.05) and 3
      weeks (P < 0.05). In contrast, we found no effects of hypoxia on the gene
      expression of VEGF and PDGF-A and -B in the lung. Our findings indicate that ET-3
      in addition to ET-1 could be involved in the process of hypoxia-induced vascular
      remodeling, whereas it appears less likely that the mitogens VEGF and PDGF-A and 
      B are essentially involved in the pathogenesis of hypoxic pulmonary hypertension.

PMID- 9574872
TI  - Pulmonary vascular resistance in dogs and minipigs--effects of hypoxia and
      inhaled nitric oxide.
AB  - The pig has been reported to present with a stronger hypoxic pulmonary
      vasoconstriction than many other species, including the dog, but it is not known
      whether this is associated with a different longitudinal partitioning of
      pulmonary vascular resistance (PVR). We investigated the relationships between
      cardiac output (Q) and mean pulmonary artery pressure (Ppa) minus occluded Ppa
      (Ppao), and effective pulmonary capillary pressure (Pc') minus Ppao, in seven
      minipigs and in seven dogs in hyperoxia (FI(O2) 0.4) and hypoxia (FI(O2) 0.1),
      first without, then with the inhalation of 80 ppm nitric oxide (NO) to inhibit
      any reversible component of PVR. Pc' was estimated from the Ppa decay curve
      following pulmonary artery balloon occlusion. In hyperoxia, minipigs compared to
      dogs had (Ppa - Ppao)/Q and (Pc' - Ppao)/Q plots shifted to higher pressures.
      Hypoxia at each level of Q increased Ppa - Ppao in minipigs more than in dogs,
      and Pc' - Ppao in minipigs only. Inhaled NO reversed hypoxia-induced changes in
      (Ppa - Ppao)/(Q and (Pc' - Ppao)/Q plots. We conclude that the minipig, compared
      to the dog, presents with higher PVR and reactivity including vessels downstream
      to the site of Pc' as determined by the arterial occlusion technique.

PMID- 9574873
TI  - Respiratory and metabolic responses of the spiny rats Proechimys yonenagae and P.
      iheringi to CO2.
AB  - The recently described burrow-dwelling Proechimys yonenagae from the Brazilian
      semiarid caatinga was compared to P. iheringi from the Brazilian rain forest of
      Mata Atlantica in terms of interactions between body temperature (Tb),
      ventilation (VE) and oxygen consumption (V(O2)) during hypercapnia (5 or 10%
      CO2). Wistar rats were also used as a control. VE was measured by
      plethysmography, Tb by inserting a probe into the colon, and V(O2) by a close
      flow system. During air breathing, VE did not differ between the rodents, Wistar
      Tb was elevated compared to P. yonenagae, and the V(O2) values of P. yonenagae
      and P. iheringi were significantly lower than those of Wistar rats. Hypercapnia
      caused hyperventilation in the three rodents, hypothermia in P. yonenage and
      Wistar rats, but no change in V(O2) was observed in any of the rodents. The
      hypercapnia-induced hyperventilation may be a major factor producing heat loss.
      This effect was independent of V(O2). Comparisons of the two spiny rat species
      suggest little adaptation of P. yonenagae to hypercapnia in burrows.

PMID- 9574874
TI  - Allergen/irritant interaction--its role in sensitization and allergic disease.

PMID- 9574875
TI  - Respiratory symptoms, bronchial responsiveness, and cellular characteristics of
      induced sputum in elite swimmers.
AB  - To investigate respiratory symptoms, increased bronchial responsiveness, and
      signs of airway inflammation in elite swimmers, we examined 29 swimmers from the
      Finnish national team and 19 healthy control subjects (nonasthmatic, symptom
      free). They answered a questionnaire and were interviewed for respiratory
      symptoms. Lung volumes were measured and bronchial responsiveness assessed by a
      histamine challenge test. Induced sputum samples were also collected. Fourteen
      (48%) of the swimmers and three (16%) of the control subjects showed increased
      bronchial responsiveness (P<0.05). The sputum cell differential counts of
      eosinophils (mean 2.7% vs 0.2%) and neutrophils (54.7% vs 29.9%) from swimmers
      were significantly higher than those from controls (P<0.01). Eosinophilia (sputum
      differential eosinophil count of >4%) was observed in six (21%) of the swimmers
      and in none of the controls (P<0.05). Symptomatic swimmers had significantly more
      sputum eosinophils than did the symptom-free. The concentrations of sputum
      eosinophil peroxidase (EPO) and human neutrophil lipocalin (HNL) were
      significantly higher in swimmers than control subjects (P<0.001 and P=0.05). We
      conclude that elite swimmers had significantly more often increased bronchial
      responsiveness than control subjects. Sputum from swimmers contained a higher
      percentage of eosinophils and neutrophils, and higher concentrations of EPO and
      HNL than sputum from controls. Long-term and repeated exposure to chlorine
      compounds in swimming pools during training and competition may contribute to the
      increased occurrence of bronchial hyperresponsiveness and airway inflammation in
      swimmers.

PMID- 9574876
TI  - Reproducibility of skin prick test results in epidemiologic studies: a comparison
      of two devices.
AB  - The reproducibility of skin prick tests under field conditions is essential for
      comparing prevalences between centers in epidemiologic multicenter studies. This
      study aimed to evaluate and compare the reproducibility of two widely used skin
      prick test devices: the Multi-Test and the ALK lancet. The subjects were 28
      children, aged 6-14 years, with known sensitivities to Dermatophagoides
      pteronyssinus (D. pter.). Both devices were applied to each subject on two
      occasions, 1 week apart, by different, randomly assigned fieldworkers, using
      histamine, negative control, and the D. pter. allergen extract. For all three
      tested solutions, mean wheal sizes were larger for the Multi-Test than for the
      ALK lancet. The coefficient of variation for histamine was 21.8% for the Multi
      Test and 17.3% for the ALK lancet. The coefficients of variation for the allergen
      D. pter. amounted to 47.4% for the Multi-Test and to 24.6% for the ALK lancet.
      The percentage of concordant test results was 92.6% for the Multi-Test and 100.0%
      for the ALK lancet for a cutoff point of wheal size equal to or greater than 1
      mm. The results of this study suggest that the single ALK lancet performs
      slightly better than the Multi-Test device with respect to reproducibility under
      conditions of epidemiologic field studies.

PMID- 9574877
TI  - In-house reference (IHR) preparation of Candida albicans allergen extract. A
      standardized extraction procedure.
AB  - A standardized, controlled procedure for preparation of an in-house reference
      (IHR) preparation of an allergen extract of Candida albicans is described. The
      procedure, based on previous studies of allergens of C. albicans, is designed to
      yield a maximum of allergens in optimum extraction conditions and to provide a
      reference preparation for further extract production. The SDS-PAGE, IgE
      immunoblotting, and crossed radioimmunoelectrophoresis (CRIE) analyses showed
      that the procedure is reproducible with acceptable batch-to-batch variation. The
      variation in the content of the most important allergens, namely, proteins with
      molecular weights of 46, 29, and 27 kDa in the pooled final batches, is
      acceptable (coeff. of variation < 15%), although in the intermediate batches of
      different strains, the coefficient of variation may occasionally exceed 20%. A
      comparison with other C. albicans allergen preparations used in our previous
      studies is also presented. The resulting extract can be used as a reference in
      further extract production and also in experimental in vitro and in vivo studies.

PMID- 9574878
TI  - Effects of topical budesonide and levocabastine on nasal symptoms and plasma
      exudation responses in seasonal allergic rhinitis.
AB  - This study compares the effects of two topical nasal treatments for allergic
      rhinitis, budesonide and levocabastine, on symptom development during seasonal
      pollen exposure. Additionally, the protective effects of drug treatments on
      allergen-challenge-induced responses (symptoms and microvascular exudation of
      plasma) are examined late into the pollen season. Forty-four patients with
      seasonal allergic rhinitis to birch pollen participated in this single-blind,
      randomized, and placebo-controlled study. Topical nasal treatment with either
      levocabastine (200 microg b.i.d.; n = 16), budesonide (200 microg b.i.d.; n =
      16), or placebo (n = 12) was instituted before the start of the pollen season and
      continued for 5 weeks until the end of the birch pollen season. The participants
      kept diaries for scores of nasal and ocular symptoms. Nasal allergen challenges
      with increasing doses of a birch pollen extract (10[2], 10[3], and 10[4] SQ-U)
      were carried out both before, when patients were asymptomatic and without
      treatment, and late into the pollen season. A nasal lavage followed each
      challenge, and the lavage fluid levels of albumin were measured as an index of
      the acute inflammatory response of the allergic mucosa. The birch pollen season
      was rather mild, producing only small increases in nasal symptoms. Budesonide
      treatment reduced the total nasal symptoms compared to placebo (P<0.01) and to
      levocabastine (P<0.05), while levocabastine treatment did not differ
      significantly from placebo. Ocular symptoms and use of rescue medication did not
      differ between placebo and the active treatments. At the end of the pollen
      season, both treatments reduced allergen-challenge-induced nasal symptoms
      compared to placebo (P<0.01). Only budesonide reduced allergen-challenge-induced
      increments of albumin levels in postchallenge nasal lavage fluids (P<0.05, in
      comparison with placebo). The results suggest that budesonide reduces both
      seasonal and allergen-challenge-induced nasal symptoms, while levocabastine is
      effective against allergen-challenge-induced symptoms also during the season. In
      addition, the topical steroid treatment, but not the antihistamine, inhibits the
      inflammatory exudation evoked by allergen challenge in patients with active
      seasonal disease.

PMID- 9574879
TI  - Efficacy and onset of action of fluticasone propionate aqueous nasal spray on
      nasal symptoms, eosinophil count, and mediator release after nasal allergen
      challenge in patients with seasonal allergic rhinitis.
AB  - We studied the effect and onset of action of fluticasone propionate aqueous nasal
      spray (FPANS) on mediator release and eosinophil accumulation in nasal secretions
      and on nasal symptoms of patients with seasonal allergic rhinitis after nasal
      allergen challenge (NAC). At the end of the pollen season, 28 patients were
      randomized in a double-blind and crossover design to receive 7 days' treatment
      with FPANS (200 microg, once daily) and matching placebo. NACs were performed
      before and at 6 h and 1, 2, 3, and 7 days during treatment with FPANS or placebo.
      Nasal secretions were collected for a quantitative determination of mediators and
      eosinophil count before and 5 min after each challenge. Nasal symptoms were
      assessed by scales grading the severity of symptoms at the same time. Results
      showed that for mediator concentrations there was a significant decrease of
      leukotriene C4 (P<0.001) at 7 days after the first administration of FPANS as
      compared to placebo. Two days after FPANS, both eosinophil counts and eosinophil
      cationic protein (ECP) concentrations were lower than those of placebo
      (eosinophils: P=0.032; ECP: P=0.038). The onset became even more important at day
      7 (eosinophils: P=0.001; ECP: P=0.009) during the FPANS treatment period. For the
      subjective nasal symptoms, a significant reduction of symptom scores for nasal
      obstruction occurred also at day 3 (P=0.017) and for sneezing at day 7 (P=0.003).
      There was not yet any significant improvement of the objective nasal airway
      resistance after the different NACs during the study period. In conclusion, this
      study demonstrated that topical fluticasone propionate is effective in the
      treatment of mucosal inflammation induced by NAC. For optimal control of nasal
      symptoms induced by repeated maximal allergen challenges, a treatment period of
      more than 1 week is required.

PMID- 9574880
TI  - Nasal inhalation of budesonide from a spacer in children with perennial rhinitis
      and asthma.
AB  - The standard treatment of allergic rhinitis and asthma consists of topical
      corticosteroids administered intranasally and inhaled through the mouth. Although
      this therapy is highly effective, and side-effects are few and mild, it may be
      possible further to improve the therapeutic index and patient compliance with the
      treatment. In the present study, we evaluated a nasal inhalation system used for
      the simultaneous treatment of rhinitis and asthma. In principle, it results in an
      airway deposition of the corticosteroid similar to that of inhaled allergens.
      Twenty-four children with perennial rhinitis and asthma inhaled budesonide
      through the nose from a pressurized aerosol, attached to a spacer device, in a
      double-blind, placebo-controlled, crossover study. Compared with placebo,
      budesonide treatment resulted in a significant reduction of nasal symptoms
      (P<0.01) and of asthma symptoms (P<0.05), and in an increase of nasal peak
      inspiratory flow (P < 0.001) and of oral peak expiratory flow (P=0.01). There
      were no differences between budesonide and placebo in local side-effects, such as
      dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a
      corticosteroid from a spacer offers a simple and effective treatment for both
      rhinitis and asthma in children, but it is an open question whether the nasal
      inhalation system can improve the ratio of antirhinitis/antiasthma effects to
      side-effects.

PMID- 9574881
TI  - Indoor allergen levels and other environmental risk factors for sensitization in
      Estonian homes.
AB  - The prevalence of allergic disease is low in Eastern Europe for reasons that are
      poorly understood. Our study aimed to investigate the levels of exposure to
      indoor allergens and living conditions among Estonian infants in relation to
      sensitization. Dust samples were collected during four winter months in 1993/94
      from the homes of 197 infants participating in a prospective study of
      sensitization. Information about living conditions was collected through a home
      visit and interviewing the mothers when the children were 6 weeks old. Three dust
      samples were collected from each home; i.e., from the infant's mattress, bedroom
      floor, and living-room carpet. The levels of allergens were determined by ELISA
      with monoclonal antibodies. The highest allergen level in a home was regarded as
      the peak value. The peak geometric mean values (+/-SD) of Der p 1 and Der f 1
      were 0.3 (0.07-1.4) microg/g dust, of Can f 1, 0.86 (0.23-3.12) microg/g dust,
      and of Fel d 1, 0.1 (0.01-0.9) microg/g dust. In 12 homes (9%), the peak value of
      house-dust mite (HDM) allergens exceeded 2 microg/g dust, with Der p 1 as the
      dominating allergen. Multivariate analyses indicated that high levels of HDM
      allergens were more common in apartments that were on the ground floor or first
      floor, that were heated with stoves, and/or that had a dampness problem. The mean
      allergen levels at home were similar in children sensitized to HDM (n=17, 0.29 vs
      0.3 microg/ g dust), dog (n=5, 0.55 vs 1.06 microg/g dust, and cat (n=18, 0.21 vs
      0.09 microg/g dust) and in children who were not sensitized to these allergens.
      Most of the sensitized children were exposed to relatively low allergen levels at
      home; i.e., below 1 microg/g dust. This level was exceeded in the homes of 4/17
      mite-, 5/18 cat-, and 0/5 dog-sensitized children. The similar levels of the
      major indoor allergens in Estonia and in Scandinavia indicate that the large
      differences in atopy prevalence among children and young adults in the two
      regions are not due to differences in allergen exposure. No allergen threshold
      level for sensitization was identified.

PMID- 9574882
TI  - Analysis of the relationships between environmental factors (aeroallergens, air
      pollution, and weather) and asthma emergency admissions to a hospital in Mexico
      City.
AB  - There have been several studies of the relationships between environmental
      factors, particularly air pollution, and attacks of asthma. Most of these studies
      have ignored the potential confounding effects of aeroallergens such as pollens
      and fungal spores. We report a statistical analysis of the relationships between
      emergency admissions for asthma to a hospital in Mexico City and daily average
      airborne concentrations of pollen, fungal spores, air pollutants (O3, NO2, SO2,
      and particulates) and weather factors. Asthma admissions had a seasonal pattern
      with more during the wet season (May-October) than the dry season (November
      April). There were few statistical associations between asthma admissions and air
      pollutants for the three age groups studied (children under 15 years, adults, and
      seniors [adults over 59 years]) in either season. Grass pollen was associated
      with child and adult admissions for both the wet and dry seasons, and fungal
      spores were associated with child admissions during both the wet and dry seasons.
      The analysis was done with environmental data averaged over the day of admission
      and the 2 previous days. Our results suggest that aeroallergens may be
      statistically associated more strongly with asthma hospital admissions than air
      pollutants and may act as confounding factors in epidemiologic studies.

PMID- 9574883
TI  - Cross-reactivity between Ficus benjamina (weeping fig) and natural rubber latex.
AB  - The importance of hypersensitivity to Ficus allergens is reported. Cross
      sensitization between fig (Ficus carica), weeping fig (F. benjamina [Fb]), and
      natural rubber latex (NRL) was confirmed by RAST inhibition. We performed skin
      prick tests with fresh Fb tree sap and NRL extracts in 346 consecutive patients
      and in 151 patients with immediate-type hypersensitivity to NRL. Total serum IgE
      and IgE antibodies to NRL and Ficus spp. were analyzed in sera. By the RAST
      inhibition method, we studied cross-reactivity among latex, fig, and weeping fig.
      Sensitization to Fb was diagnosed in 23 of the 346 consecutive patients, and the
      simultaneous presence of latex-specific IgE was highly significant. Of 151 NRL
      allergic patients, 35 were also sensitized to Fb. Cross-reacting IgE antibodies
      recognizing latex and Ficus allergens were demonstrated by RAST inhibition. The
      present study reinforces the importance of Fb as an indoor allergen. Cross
      reacting IgE antibodies to NRL and Ficus spp. allergens are frequently found in
      the sera of atopic patients. Development of commercially available standardized
      extracts for skin tests is urgently necessary.

PMID- 9574884
TI  - The in vivo effect of isocyanate-induced asthma on basophil histamine release.
AB  - In vitro studies have suggested that basophils are involved in the asthmatic
      response to isocyanate. Classified by the type of airway response, three groups
      of patients exposed to isocyanate were studied: 1) nonreactive (n=3), 2)
      immediate responders (n=4), and 3) late responders (n=4). Basophil histamine
      release to concanavalin A (conA), FMLP, and anti-IgE was evaluated before and
      during the airway response. Histamine release significantly (P=0.009 for conA and
      0.03 for anti-IgE) increased after exposure to isocyanate only in the group which
      had late bronchial response. Additionally, good correlation was found between
      baseline FEV1/FVC% and degree of histamine release of basophils stimulated with
      conA. These findings support a role for basophils in the late asthmatic response
      to isocyanate.

PMID- 9574885
TI  - Effects of various vacuum cleaners on the airborne content of major cat allergen
      (Fel d 1).
AB  - BACKGROUND: It has been shown that a vacuum cleaner (VC) can increase airborne
      cat allergen levels. This study aimed to compare the degree of leakage of
      airborne Fel d 1 levels among five different VCs, both under laboratory
      conditions and in an apartment with cats. METHODS: Three of the VCs were marketed
      as antiallergic: a HEPA filter VC (VC A), a water impingement and HEPA filter VC
      (VC B), and a foam fabric filter VC (VC C). The other two were standard VCs: VC D
      and VC E. VCs were tested in a 20 m3, airtight, experimental room and in a 53 m3
      living room in an apartment with three cats. Air was sampled with a glass-fiber
      filter and an impinger at 20 l/min for 30 min before, during, and after
      vacuuming. Airborne Fel d 1 was measured with a two-site monoclonal ELISA assay.
      RESULTS: In the experimental room, no airborne Fel d 1 level was measured before
      using the VCs. After introducing a dust sample containing Fel d 1 in the VCs, we
      found that VCs A, B, and E did not provoke any increase in airborne Fel d 1. In
      contrast, VCs C and D significantly increased airborne Fel d 1 levels (GM: 4.9
      and 5.3 ng/m3, respectively). In the apartment, all VCs induced an increase in
      airborne Fel d 1, which was carried by particles greater than 5 microm. However,
      VCs C and D provoked significantly greater increases in airborne Fel d 1 than VCs
      A, B, and E (P=0.0001). CONCLUSIONS: Our results suggest that: 1) The two VCs
      with leakage in the experimental room had greater leakages in the apartment. 2)
      In the apartment with cats, all VCs provoked increases in airborne Fel d 1,
      primarily carried by large particles. 3) Given the increased marketing of
      "antiallergic" VCs, further studies are needed to standardize methods for testing
      airborne allergen leakage by VCs.

PMID- 9574886
TI  - Serum eosinophil cationic protein in the evaluation of asthma severity in
      children.
AB  - To assess the sensitivity and specificity of serum eosinophil cationic protein
      (ECP) in the diagnosis of asthma and evaluation of asthma severity, we conducted
      a prospective study to compare parameters of asthma severity, peripheral blood
      eosinophilia, and serum ECP concentrations in 88 children presenting to a
      university hospital outpatient clinic with suspected (n=59) or recently diagnosed
      asthma (n=29). Serum ECP correlated significantly (r[s]=0.676, P = 0.0001) with
      peripheral eosinophil counts, but only weakly with asthma severity (r[s]=0.21,
      P=0.046). Serum ECP was significantly higher in atopic children (25+/-11
      microg/l) than in nonatopic children (16+/-15 microg/l) (P=0.01). Bronchial
      hyperresponsiveness had no significant correlation (r[s]= -0.21, P=0.30) with
      serum ECP. Lung function test results had no (peak flow) or only a weak (FEV1)
      correlation with serum ECP. In distinguishing between children with and without
      asthma or in assessing asthma severity, serum ECP is not superior to the
      peripheral blood eosinophil count. The diagnostic sensitivity and specificity of
      ECP in serum for detecting symptomatically active asthma, evaluated against the
      cutoff level of ECP in serum of 16 mg/l, were 54% and 71%, respectively.

PMID- 9574887
TI  - Prevalence of sensitization to the storage mites Acarus siro, Tyrophagus
      putrescentiae, and Lepidoglyphus destructor in allergic patients with different
      degrees of sensitization to the house-dust mite Dermatophagoides pteronyssinus.
AB  - The prevalence of sensitization to the storage mites Acarus siro (AS), Tyrophagus
      putrescentiae (TP), and Lepidoglyphus destructor (LD) was studied in 250 sera of
      patients with different degrees of sensitization to the house-dust mite
      Dermatophagoides pteronyssinus (DP) by measuring IgE binding to extracts of the
      storage mites. Additionally, allergenic cross-reactivity between DP and the
      storage mite species was studied by RAST inhibition with five individual sera
      (and a pool of these sera) with moderate IgE levels to all three storage mites
      and to DP. Increased serum IgE to storage mites was found in 46% of the 200
      patients sensitized to DP. Increased prevalence rates of IgE titers to storage
      mites were associated with higher IgE levels to DP. In 50 sera without
      sensitization to DP, only five sera showed increased IgE to one of the storage
      mites. Extracts of TP almost completely inhibited the IgE binding to AS, and vice
      versa. DP inhibited IgE binding to all storage mites up to 60%, whereas IgE
      binding to DP was only minimally inhibited by extracts of storage mites. In
      conclusion, cosensitization to storage mites is a frequent finding in patients
      sensitized to DP. Although this is largely the result of cross-reactivity between
      different mite species, it may nevertheless be of clinical significance in
      patients exposed to storage mites.

PMID- 9574888
TI  - Growth inhibition of fibroblasts from nasal polyps and normal skin by lysine
      acetylsalicylate.
AB  - Some authors have shown that lysine acetylsalicylate (LAS) may help prevent nasal
      polyp relapses. As some anti-inflammatory drugs have been found to regulate cell
      growth, we investigated the antiproliferative effect of LAS on fibroblasts
      derived from nasal polyps. Moreover, we studied the effect of LAS on the growth
      of fibroblasts derived from normal skin to determine whether the response was
      similar to that obtained in the above-mentioned cells. Fibroblasts were obtained
      from tissue samples of nasal polyps from two aspirin-tolerant and two aspirin
      intolerant patients, and from the normal skin of a healthy donor. The cells were
      treated with LAS (20-2000 microg/ml of culture medium). Cell growth and viability
      were evaluated after 3 and 6 days of culture. LAS had a growth-inhibitory effect
      on cells independently of their derivation. A reduction in cell growth was seen
      at the concentrations of LAS tested, which correspond to those used in the local
      treatment of nasal polyposis.

PMID- 9574889
TI  - Clinical effects of benzyl benzoate in the prevention of house-dust-mite allergy.
      Results of a prospective, double-blind, multicenter study.
AB  - The efficacy of the acaricide benzyl benzoate as an additive to a chemically and
      technically defined cleaning substance (Acarosan) was tested in a multicentric,
      prospective, randomized, controlled study on 118 outpatients with bronchial
      asthma due to house-dust-mite allergy. Subjective reports from patients and
      doctors revealed an improvement in clinical complaints in more than 50%, with
      only small differences between the verum and the placebo group. Objective
      parameters such as titrated skin tests, RAST, and bronchial challenge tests with
      histamine and Dermatophagoides pteronyssinus (D. pt.) did not reveal any
      significant changes either during the year of testing or between the two groups.
      A clinical improvement as observed in either group could not be assessed by
      objective parameters. Additional questions as to the merits of the possible
      prophylactic use of benzyl benzoate over more than 1 year remain unanswered.

PMID- 9574890
TI  - Results of wearing test with two different latex gloves with and without the use
      of skin-protection cream.
AB  - A total of 109 subjects reporting symptoms indicating type I hypersensitivity
      reactions to natural rubber latex (NRL) gloves was included in this study, and 66
      of them had latex-specific IgE antibodies. They underwent provocation tests by
      wearing two types of NRL gloves with high (n=103) and low (n=75) allergen
      contents. The first glove type caused positive skin reactions in 30% of IgE
      positive and in 3% of IgE-negative subjects. After application of a commercially
      available skin protection (barrier) cream, the frequencies of positive skin
      responses in wearing tests increased to 41% and 7%, respectively. The gloves with
      low allergen content did not cause hypersensitivity without skin-protection cream
      but induced responses in 5% of IgE-positive subjects when this cream was applied.
      Corresponding findings were obtained in intraindividual comparisons of test
      results, which were possible in 69 cases. Of all wearing-test responders, 92% had
      latex-specific IgE antibodies. Our results demonstrate that high allergen
      contents in latex gloves frequently elicit skin responses in NRL-sensitized
      subjects, and that skin-protection creams may favor the uptake of allergens from
      gloves, thus increasing allergic reactions. The stipulation of a legally binding
      threshold limit value (TLV) for allergens in NRL products is urgently needed.
      This TLV should not be set above 2 microg allergen/g rubber.

PMID- 9574891
TI  - Natural rubber-latex allergy in patients not intensely exposed.
AB  - Immediate-type allergy to natural rubber latex (NRL) is common in highly exposed
      groups, particularly in health-care workers and patients with spina bifida. The
      occurrence of NRL allergy was investigated in subjects not belonging to such risk
      groups. A total of 493 patients presenting with various diseases for allergologic
      evaluation was studied. A questionnaire-based history was taken, skin prick tests
      with NRL milk and common aeroallergens were done, and NRL-specific serum IgE
      antibodies were measured. A total of 317 subjects (64.3%) was atopic. There were
      skin prick test reactions to NRL in 80 (16.2%) and NRL-specific IgE in the serum
      in 79 (16.0%) subjects; both were found in 25 patients (5.1%). Altogether, NRL
      sensitization was found in 134 patients (27.2%). By history and/or challenge
      tests, 13 subjects (2.6%) were diagnosed as having clinically relevant NRL
      allergy. In five of these, anaphylactic reactions had occurred during dental
      procedures, and in four during general anesthesia; 10 subjects reported immediate
      type reactions to NRL products in daily life. All patients with clinically
      relevant NRL allergy had a skin prick test reaction to NRL milk (sensitivity
      100%). Nine had specific IgE antibodies in the serum (sensitivity 69.2%);
      respective specificity was 86.0% or 85.4%. Nine of the 13 patients (69.2%) with
      NRL allergy were atopic. Despite exclusion of those at risk, many patients had
      clinically relevant allergy to NRL, and many of these had had severe reactions.
      NRL allergy is an important health issue also beyond the known risk groups.

PMID- 9574892
TI  - Escribano-Rodriguez et al. present an interesting report of a boy who had
      allergic symptoms, mainly urticaria, due to maggots when fishing (AllergyNet
      1997;52:1038)

PMID- 9574893
TI  - Oral allergy syndrome to grapes.

PMID- 9574894
TI  - Anaphylaxis to curry powder.

PMID- 9574895
TI  - Latex allergy among nurses in an operating unit.

PMID- 9574896
TI  - Latex/chlorhexidine-induced anaphylaxis in pregnancy.

PMID- 9574897
TI  - Paracetamol sensitivity without aspirin intolerance.

PMID- 9574898
TI  - IgM to Bartonella henselae in cat-scratch disease and during acute Epstein-Barr
      virus infection.
AB  - The diagnostic value of IgM to Bartonella henselae was evaluated in 20 children
      with cat-scratch disease (CSD) and controls consisting of 20 blood donors and 20
      children with enlarged lymph nodes without CSD by two indirect immunofluorescence
      assays (IFA). One was based on B. henselae cocultivated with Vero cells (host
      cell-associated IFA), and the other on B. henselae grown on agar (host cell-free
      IFA). With the host cell-associated IFA, 18 of 20 children with CSD revealed IgM,
      whereas only 14 did so with the host cell-free IFA. Sera of two blood donors as
      well as sera from three children with enlarged lymph nodes without CSD showed
      also positive IgM to cell-associated B. henselae. This study reveals that the IFA
      applied had sensitivities of 70-90% and specificities of 87.5-100% for detecting
      IgM to B. henselae. Additionally, 20 patients with IgM to Epstein-Barr virus
      (EBV) capsid antigen were tested for IgM to B. henselae. Sera of 16 and 9 of
      these patients revealed IgM to B. henselae with the host cell-associated and the
      host cell-free IFA, respectively. Using Western blot these sera were demonstrated
      to react against linearized proteins of Vero cells and of B. henselae. Thus,
      since acute EBV infection may substantially reduce the specificity of B. henselae
      specific IgM tests, we conclude that diagnosis of CSD should be confirmed by a
      significant IgG titer to B. henselae or by detection of this pathogen.

PMID- 9574899
TI  - First characterization of Borrelia burgdorferi sensu lato from ticks and skin
      biopsy in Bulgaria.
AB  - Lyme borreliosis is the most frequent tick-borne disease in the Northern
      hemisphere. Here we describe the first isolation of Borrelia burgdorferi sensu
      lato in Bulgaria: the midguts of 47 Ixodes ricinus obtained by flagging from the
      Central park in Sofia, Bulgaria were cultivated for borreliae in BSK medium. The
      eight isolates obtained from the ticks and one skin isolate from a Bulgarian
      patient with erythema migrans were subjected to phenotypic [outer surface protein
      A (OspA) serotyping] and genotypic analysis (pulsed-field gel electrophoresis
      typing followed by large restriction fragment pattern analysis after MluI
      digestion, polymerase chain reaction with 16S rRNA-directed oligonucleotide
      probes, and restriction fragment length polymorphism analysis of rrf-rrl
      intergenic spacer amplicons). The skin isolate was B. burgdorferi sensu stricto,
      as were four of the tick isolates; the other four tick isolates were B. garinii
      representing three different OspA serotypes (types 3, 5 and 7). These findings
      confirm the wide geographic distribution of the different B. garinii-associated
      OspA serotypes in Europe (shown here for the first time for the Southeastern part
      of Europe) and of B. burgdorferi sensu stricto in the Western hemisphere. These
      findings have implications for development of diagnostic tests and a borrelia
      vaccine in Southeastern Europe.

PMID- 9574901
TI  - Persistent parvovirus B19 infections in immunocompromised children.
AB  - Immunocompromised patients have been shown to suffer from prolonged viral
      infections often without detectable immune response. Here chronic infections with
      low virus levels can be frequently observed. In these patients viral DNA can be
      detected over long periods by polymerase chain reaction (PCR). In this study
      parvovirus B19 presence was assessed by PCR, immunoblot and enzyme-linked
      immunosorbent assay in sera from children with mainly oncological and
      hematological diseases. In 45% of sera B19 DNA was observed. Of the children 25%
      had IgG antibodies to viral protein 1 and 2 (VP1/2) and 15% to nonstructural
      protein 1 (NS1). In 6% of children IgM antibodies to VP1/2 were detected. These
      results indicate that the number of children with immune response to B19 proteins
      is distinctly lower than the number of children with B19 DNA. Transfusions of
      blood products might have been a possible route for B19 infection. Establishment
      and maintenance of a persistent parvovirus B19 infection with or without immune
      response are enhanced in the analyzed immunocompromised children in comparison
      with immunocompetent children. A persistence of B19 DNA was demonstrated up to 10
      months in patients sera.

PMID- 9574900
TI  - Hemolytic properties and riboflavin synthesis of Helicobacter pylori: cloning and
      functional characterization of the ribA gene encoding GTP-cyclohydrolase II that
      confers hemolytic activity to Escherichia coli.
AB  - Various strains of Helicobacter pylori were able to lyse erythrocytes from sheep,
      horse, and human when grown on blood agar. The hemolysis did not depend on the
      production of the vacuolating cytotoxin VacA as demonstrated by the hemolytic
      behavior of an isogenic vacA-negative mutant strain. The hemolytic activity could
      be detected in cell-free supernatants and was not regulated by iron. To isolate
      genes coding for proteins involved in the destruction of erythrocytes, a plasmid
      based DNA library was screened for expression of lytic activity on blood agar.
      This approach revealed that the H. pylori ribA gene confers hemolytic properties
      to Escherichia coli. The ribA gene encodes the enzyme GTP-cyclohydrolase II [EC
      3.5.4.25] that catalyzes the initial step in the synthesis of riboflavin. The
      predicted amino acid sequence of the H. pylori RibA protein showed a high degree
      of similarity to equivalent enzymes from microorganisms and from plants. The
      single gene on a plasmid restored riboflavin synthesis in a ribA mutant of E.
      coli and induced hemolytic activity. Furthermore, ribA overexpression was
      associated with the production of a fluorescent yellow molecule that was not
      identical with riboflavin. Hemolysis was also seen for the ribA gene from E.
      coli, indicating that this feature was not specific for the H. pylori gene. The
      presence of ribA in various H. pylori strains was confirmed by Southern blot
      hybridization and by polymerase chain reaction with specific primers. This
      analysis revealed that microdiversity exists within the DNA region upstream from
      ribA, which was further confirmed by nucleotide sequence analysis.

PMID- 9574902
TI  - Lack of antiviral effect of amantadine in Borna disease virus infection.
AB  - The antiviral effect of amantadine (1-aminoadamantane) was tested in vitro as
      well as in vivo. Treatment of persistently Borna disease virus (BDV)-infected
      cell lines of different origin and for various length of time did not result in a
      general reduction of virus titer or clearance of virus from infected cells. In
      vivo, rats were treated with amantadine by daily oral application or by use of
      osmotic pumps, and in both cases treatment was started before infection. Neither
      route of application of the drug had any influence on the time of onset of
      disease, on antiviral antibody titers, on virus titer in the brain, on the
      severity of the inflammatory reaction in the brain, or on the severity of
      neurological symptoms. These experiments, although revealing negative results and
      obtained using a virus from a natural case of Borna disease grown after isolation
      in vitro for a long period of time, should caution from the general use of
      amantadine as a curative agent against BDV infection as has been implicated
      recently [Bode et al. (1997) Lancet 349:178-179].

PMID- 9574904
TI  - Genetic polymorphism of Leishmania species using kinetoplast DNA restriction
      fragment length polymorphism and cDNA probe of Leishmania donovani.
AB  - Leishmaniasis represents a group of diseases that range from simple cutaneous
      lesions through metastasizing diffused cutaneous to severe systemic infection
      depending upon the taxon to which the causative parasite belongs. Therefore, it
      is important to identify the infecting Leishmania. Methods presently being used,
      including immunology, biochemistry and molecular biology have one or the other
      limitations, leaving scope for the search for newer probes. This study reports
      the characterization of leishmania isolates both by restriction fragment length
      polymorphism of kinetoplast DNA (kDNA) and genomic DNA. The genomic DNA was
      probed with a cDNA probe B2a1. Using a kDNA restriction pattern technique,
      different isolates of Leishmania donovani could be differentiated from the UR6
      strain of L. tropica, but it was not possible to differentiate between newer
      local isolates of L. donovani with most of the restriction enzymes except AluI.
      However, the B2a1 cDNA probe was able to differentiate these isolates
      effectively. Both of these techniques could differentiate newer local isolates of
      L. donovani from the older isolates of L. donovani from India, i.e., DD8, RMRI
      and SS. The Indian isolates of L. donovani could also be differentiated from
      isolates of L. donovani from Jeddah and Germany using both techniques. The
      present study indicates that the cDNA probe B2a1 can be used as an important
      adjunct to kDNA restriction analysis for the characterization of Leishmania
      species.

PMID- 9574903
TI  - HIV-1 Nef binding protein expressed on the surface of murine blood cells.
AB  - The Nef protein of HIV-1 binds to and induces apoptotic cytolysis of a broad
      spectrum of uninfected blood cells of humans and mice independently of CD95
      (Fas). A 24-kDa glycoprotein responsible for Nef binding and the Nef-induced
      apoptosis has been identified on the surface of human CD4+ T cells. Using mouse
      monoclonal antibodies (mAbs) against the human Nef-binding protein and flow
      cytometry, we analyzed the expression of a corresponding protein on murine cells.
      The mAbs were shown to bind to the surface of various murine cell lines including
      T and B lymphocytes and macrophages, in a fashion similar to the binding by
      soluble Nef protein. The mAbs competed with the Nef protein in binding to the
      cell surfaces. Immunoprecipitation of cell membranes revealed a 25-kDa protein
      recognized by the mAbs. Treatment of the soluble Nef protein with anti-Nef (C
      terminus) mAb, but not anti-Nef (N terminus) mAb, deprived the Nef of the cell
      binding activity, indicating that binding site is located in the C-terminal
      domain. Cross-linking of the cell-bound mAbs with secondary antibodies induced
      apoptotic cytolysis, which occurred independently of CD95 (Fas). On the other
      hand, neither the mAbs nor the soluble Nef protein reacted with primary
      lymphocytes in a resting stage obtained from lymph nodes, thymus and spleen of 5
      week-old mice. However, some of the cells, predominantly comprising CD4+ T cells,
      became positive for the both reactions after mitogenic stimulation with
      phytohemagglutinin, concanavalin A or lipopolysaccharide of Escherichia coli.
      These results suggest that the 25-kDa protein on murine cell surfaces corresponds
      to the human Nef binding protein and is responsible for the Nef-induced
      apoptosis, and that its expression on the cell surface depends on cellular
      activation.

PMID- 9574905
TI  - Expression of the mammalian calcium signaling response to Trypanosoma cruzi in
      Xenopus laevis oocytes.
AB  - Infective stages of the protozoan parasite Trypanosoma cruzi contain a soluble
      factor that induces elevation in the intracellular free Ca2+ concentration
      ([Ca2+]i) of mammalian cells. The process is pertussis toxin (PTx)-sensitive, and
      involves phospholipase C (PLC) activation, inositol 1,4,5-trisphosphate (IP3)
      formation and Ca2+ release from intracellular stores (Tardieux I, et al. J Exp
      Med 1994;179:1017-1022; Rodriguez A, et al. J Cell Biol 1995;129:1263-1273). We
      now report that a molecule exposed on the surface of the target cells is required
      to trigger the signaling cascade, and that a response with identical
      characteristics can be induced in Xenopus laevis oocytes injected with mRNA from
      normal rat kidney (NRK) fibroblasts. Xenopus oocytes do not show an endogenous
      response to the trypomastigote Ca2+ signaling factor, but a vigorous response in
      the form of a propagating Ca2+ wave is expressed after injection of NRK cell
      mRNA. As previously demonstrated for mammalian cells, the response is inhibited
      when injected oocytes are pretreated with PTx, implicating Galphai or Galphao
      trimeric G-proteins, and with thapsigargin, which depletes intracellular Ca2+
      stores. Moreover, the [Ca2+]i transients triggered by the T. cruzi soluble factor
      in mRNA-injected oocytes are blocked by the same inhibitors of the parasite
      oligopeptidase B that abolish the [Ca2+]i response in NRK cells (Burleigh B,
      Andrews NW. J Biol Chem 1995;270:5172-5180; Burleigh BA et al. J Cell Biol
      1997;136:609-620). The NRK mRNA fraction that induces expression of the [Ca2+]i
      response to the T. cruzi signaling factor contains messages from 1.5 to 2.0 kb, a
      size range consistent with the family of seven-transmembrane G-protein-coupled
      receptors.

PMID- 9574907
TI  - Subunit 9 of the mitochondrial ATP synthase of Trypanosoma brucei is nuclearly
      encoded and developmentally regulated.
AB  - We have previously shown that the mitochondrial ATP synthase is developmentally
      regulated through the life cycle of Trypanosoma brucei. The mechanism of this
      regulation is as yet unknown. We are currently examining regulation of expression
      of several key subunits of the ATP synthase to investigate this mechanism. In the
      work presented here, we have cloned, sequenced, and confirmed the identity of the
      ATPase subunit 9 homologue from T. brucei. The ATPase subunit 9 gene that we have
      identified from T. brucei has between 40 and 600% identity with subunit 9 from a
      variety of organisms. This gene possesses a putative mitochondrial import
      sequence at the N terminus of the encoded protein sequence. The protein expressed
      from this gene by in vitro transcription/translation comigrates with native
      protein isolated from inner mitochondrial membrane vesicles from T. brucei. We
      have shown that the cDNA identifies a copy of this gene in the nuclear genome,
      but does not identify a similar gene in kinetoplast DNA (kDNA) prepared from T.
      brucei. This gene does not show homology to any published sequence data from
      maxicircle DNA or edited maxicircle derived sequences. Steady state transcripts
      of a single size have been identified by Northern analysis and demonstrate
      significant developmental regulation through the T. brucei life cycle. Northern
      analysis and quantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) results show that the transcript is 10-14-fold higher in procyclic form than
      in early and late bloodstream forms.

PMID- 9574906
TI  - Differentially expressed genes in the Trypanosoma brucei life cycle identified by
      RNA fingerprinting.
AB  - RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR) was
      used to identify genes that were differentially expressed during the life cycle
      of Trypanosoma brucei, as well as in response to heat shock. The standard RAP-PCR
      protocol was varied in two ways. First, the PCR reactions sometimes included a
      primer derived from the 5' mini-exon sequence, to ensure that most of the
      products contained the 5' end of mRNAs. Second, differentially amplified products
      were reamplified, isolated on single strand conformation polymorphism (SSCP)
      gels, cloned, and sequenced. Clones representing 32 different expressed sequence
      tags (ESTs) were obtained. Twenty-four ESTs were confirmed as differentially
      expressed by RT-PCR between different stages of the parasite cycle, or in
      response to temperature elevation. Nine clones had significant similarities to
      sequences already in the database. These transcripts included genes encoding cell
      surface proteins, metabolic enzymes, and heat shock proteins, either from
      trypanosomes or other organisms. Of particular interest, ESAG1 was shown to be
      heat-inducible in the procyclic stage. Most of the transcripts were unrelated to
      any other sequences in the database, and were deposited as new ESTs. The
      identification of stage-specific and heat shock-regulated transcripts will
      complement the growing T. brucei database. In addition, this experimental
      approach allows previous entries in the sequence database to be annotated with
      regulatory information.

PMID- 9574908
TI  - Intraerythrocytic expression of topoisomerase II from Plasmodium falciparum is
      developmentally regulated.
AB  - The stage-specific relationship between promoter activity, transcript production,
      protein expression and enzyme activity has been investigated for the gene
      encoding Plasmodium falciparum topoisomerase II (PfTopoII). Nuclear run-on
      experiments have shown that the P. falciparum topoisomerase II gene (PfTOP2)
      promoter is active at low levels in ring stage parasites, but reaches high levels
      of activity as the parasites progress into trophozoite/schizont asexual stages.
      Steady-state PfTOP2 transcripts are present at low levels in rings, accumulate in
      trophozoites, but are completely undetectable in schizonts. An antiserum raised
      against the species-divergent carboxy-terminus of PfTopoII, which neutralised the
      decatenation activity in parasite extracts, was used to probe Western blots of
      ring, trophozoite and schizont stage parasite extracts. Relatively low levels of
      PfTopoII were seen in rings compared with those in trophozoite and schizont
      preparations. Parasite extracts were also used to compare the patterns of protein
      accumulation and enzyme activity at these stages. Complete decatenation of
      kinetoplast substrate DNA (KDNA) was found in schizont stages, very low levels of
      activity were observed in rings and trophozoites showed intermediate levels.
      These finding show that, as parasites progress towards the stages where DNA
      replication occurs, there is a concomitant increase in both topoisomerase II
      production and activity.

PMID- 9574909
TI  - Characterization and cloning of the gene encoding the vacuolar membrane protein
      EXP-2 from Plasmodium falciparum.
AB  - As a contribution to the characterization of the parasitophorous vacuolar
      membrane from Plasmodium falciparum we have begun the identification of vacuolar
      membrane proteins. Exported protein-2 (EXP-2) is a vacuolar membrane protein
      exposed into the vacuolar space. To further characterize EXP-2, it was purified,
      and the 45 N-terminal amino acids were determined by micro-sequencing. Based on
      this information, partial cDNA and genomic fragments were amplified by PCR and
      used as probes for the isolation of complete cDNA and genomic DNA clones. The
      single copy gene is located on chromosome 14, and is transcribed during the ring
      stage of parasite development. The open reading frame encodes an N-terminal
      signal sequence which is cleaved from the mature protein. The amino acid
      composition of EXP-2 is characterized by charged amino acids, with a high
      abundance of aspartate residues in the C-terminal portion of the protein. In
      contrast to EXP-1, an integral protein of the vacuolar membrane, EXP-2 lacks a
      typical hydrophobic transmembrane domain. We suggest that EXP-2 may associate
      with the vacuolar membrane via an amphipathic helix located in the N-terminal
      half of the protein.

PMID- 9574910
TI  - Episomal and integrated maintenance of foreign DNA in Giardia lamblia.
AB  - Giardia lamblia is an early diverging eukaryote which causes gastrointestinal
      disease throughout the world. Different subgroups of Giardia have been defined
      based on several biochemical and genetic criteria. We have developed a method for
      stably introducing DNA into the nuclei of the parasite using puromycin
      acetyltransferase (pac) as a dominant selectable marker. Transfected circular
      DNAs were maintained as episomes in the isolate WB, a representative of one
      Giardia subgroup. When input DNAs were linearized, integration was observed to
      occur by homologous recombination producing gene replacements in this isolate. In
      isolate GS, which represents a different subgroup, both linear and circular
      transfected DNAs were integrated into the genome by homologous recombination. In
      GS, linear DNA again produced gene replacements, while circular DNA produced
      duplicative integration events. The failure of GS to replicate episomes may
      reflect differences in the structure or recognition of DNA replication origins
      between these subgroups. A plasmid shuttle vector was also developed for
      expression of other genes in Giardia lamblia. Utilizing the green fluorescent
      protein as a reporter gene in the WB isolate, we show that gene expression from
      this vector correlated with plasmid copy number over a range of two orders of
      magnitude. Together these tools should greatly enhance our ability to study both
      the basic biology and the pathogenesis of this ubiquitous parasite.

PMID- 9574911
TI  - Heterogeneity in the circumsporozoite protein gene of Plasmodium malariae
      isolates from sub-Saharan Africa.
AB  - Polymorphism of the circumsporozoite protein (CSP) of Plasmodium malariae was
      characterized by comparing gene sequences of twelve field isolates obtained in
      Yaounde, Cameroon, Central Africa, and one clinical isolate originating from Cote
      d'Ivoire, West Africa. The length of the CSP gene ranged from 1266 to 1302 bp.
      The size polymorphism was due to variation in the number of tandem repeat units.
      All P. malariae isolates displayed a highly conserved 5' non-repeat region. Seven
      non-synonymous and two synonymous nucleotide variations were observed in the 3'
      non-repeat region. In the deduced amino acid sequence the repetitive sequences
      consisted of a varying number of major (Asn Ala Ala Gly (NAAG); range between 42
      and 46 units) and minor (Asn Asp Ala Gly (NDAG) or Asn Asp Gln Gly (NDEG); n =
      six or seven units) tetrapeptide units. None of the isolates had an identical
      sequence at nucleotide level. These findings suggest that polymorphism in CSP is
      essentially limited to the tandem repeat domain.

PMID- 9574912
TI  - Developmental regulation of two nuclear RNA binding proteins, p34 and p37, from
      Trypanosoma brucei.
AB  - We have previously reported the purification of two closely related nucleic acid
      binding proteins, p34 and p37, from Trypanosoma brucei and the cloning and
      sequencing of the two genes encoding these two proteins. The predicted primary
      structures of the two proteins are nearly identical with one major and several
      minor differences. Three sequence motifs have been identified in both proteins:
      an N-terminal alanine, proline, and lysine rich domain, one and a half internal
      consensus RNA binding domains, and a C-terminal KKDX repeat region. p34 and p37
      bind preferentially to heterogeneous RNA as compared with other nucleic acids.
      Here, we report the developmental regulation of the expression of these two
      highly related proteins and their intracellular localization in T. brucei. The
      results indicate that these two RNA binding proteins are differently regulated
      through the Trypanosoma brucei life cycle. The steady state level of p34
      transcript and protein are highest in the procyclic form. In bloodstream form,
      however, the p34 message is readily detectable, while the protein is not
      detectable. The p37 transcript level is nearly as high as that for p34 in
      procyclic form, while the p37 protein level is low. In bloodstream form p37
      protein does correlate with the relative abundance of the steady state mRNA
      level. The two proteins have been localized to the nucleus by immunofluorescent
      confocal microscopy and subcellular fractionation.

PMID- 9574914
TI  - Proton-ATPase activities involved in the uptake of an S-adenosylmethionine
      analogue.
AB  - Characteristics of the transport of sinefungin (SF) were studied in Leishmania
      donovani promastigotes grown in vitro in a semi-defined medium. The uptake is
      time and pH dependent, temperature sensitive, saturable and independent of the
      growth phase. Metabolic inhibitors decrease the influx, indicating that
      sinefungin uptake is an energy requiring process. The presence of Na+ is
      unnecessary for activity. The uptake is sensitive to valinomycin and nigericin
      and to the H+-ATPases inhibitors such as N'N'-dicyclohexylcarbodiimide,
      bafilomycin A and oligomycin. Sulfhydryl group(s) are involved in carrier
      activity. Use of SF analogues shows, stereospecificity of the transporter,
      recognition of the 6'-amino group and to a lesser degree of the 9'-amino group of
      the lateral chain, whereas the 9'-carboxyl group of the lateral chain is not
      implicated in the recognition. Adenosine and ornithine do not interfere with the
      uptake. No significant amount of SF is tightly bound to macromolecules. In a SF
      resistant clone, though the uptake of SF is reduced (the apparent Vmax is 276
      pmoles mg protein(-1) 30 min(-1) compared with 2061 pmoles mg protein(-1) 30 min(
      1) for the wild-type clone), the apparent affinity for SF is similar to that of
      wild-type cells (Km 0.7 and 0.6 microM respectively). This lower uptake activity
      is not the reflection of an increased efflux of the drug. In these resistant
      cells, the susceptibility of SF uptake to variation of the external pH, as well
      as to azide, NaF, and valinomycin are decreased, that to nigericin is lost.

PMID- 9574913
TI  - Characterisation of PfSec61, a Plasmodium falciparum homologue of a component of
      the translocation machinery at the endoplasmic reticulum membrane of eukaryotic
      cells.
AB  - Plasmodium falciparum secretes several proteins that cause changes in the
      erythrocyte membrane enabling it to survive within red blood cells. Little is
      known of the mechanisms involved in the secretion and targeting of parasite
      polypeptides to the various cell compartments. The P. falciparum gene homologous
      to the mammalian Sec61alpha, gene, which encodes a component of the translocation
      pore in the endoplasmic reticulum of eukaryotic cells, was characterised to
      investigate the translocation process in the parasite. PfSec61 is present as a
      unique copy in the parasite genome and was mapped to chromosome 13. It encodes a
      40 kDa polypeptide, as shown by immunoblotting and immunoprecipitation of
      [35S]methionine metabolically-labelled parasite extracts. The deduced amino acid
      sequence of PfSec61 is 87% similar to the mammalian polypeptide, and the two
      proteins give similar hydropathy plots. These results strongly suggest that
      PfSec61 has the same topological orientation and functional role as Sec61alpha.
      Anti-PfSec61 antibodies were used to investigate the cellular location and
      kinetics of expression of the polypeptide in the parasite. Immunofluorescence
      confocal microscopy showed that PfSec61 was located in the parasite cytoplasm,
      close to the nucleus, in a position consistent with its being in the endoplasmic
      reticulum.

PMID- 9574915
TI  - Analysis of the processing of Plasmodium falciparum rhoptry-associated protein 1
      and localization of Pr86 to schizont rhoptries and p67 to free merozoites.
AB  - The processing and localization of Plasmodium falciparum rhoptry-associated
      protein 1 (RAP-1) products were examined using polyclonal and monoclonal
      antibodies raised to a recombinant protein containing residues 1-294 of RAP-1.
      Immunoblot and epitope mapping results with antibodies that selectively bound
      epitopes in the RAP-1 products Pr86, p82, and p67 showed that p82 and p67 are
      formed from Pr86 by progressive removal of epitopes from the amino-terminus of
      the RAP-1 coding sequence. The capacity of Pr86 to form complexes was revealed
      after size fractionation of parasite proteins radiolabeled in the presence of
      brefeldin A to prevent processing of Pr86. Fractions containing complexed Pr86
      also contained the RAP-2 product p39 and the RAP-3 product p37, suggesting that
      Pr86, p39 and p37 may form complexes similar to complexes previously reported for
      p82 and p67 with p39 or p37. Immunofluorescence localization and immunoblot
      studies revealed that Pr86 is present in the rhoptries, but only transiently, and
      that it is not detected in segmenting schizonts or extracellular merozoites. p67
      and p82, on the other hand, were shown to be major RAP-1 components in purified
      merozoites. Neither p67 nor p82 were relocalized from the intracellular rhoptries
      to the merozoite surface under conditions that promoted relocalization of the
      rhoptry protein PF83/apical membrane antigen 1. These results suggest that
      processing of Pr86 begins after Pr86 complexes are transported to the forming
      rhoptries and that two site-selective processing reactions occur in the
      rhoptries, a rapid cleavage of Pr86 to p82 and a delayed cleavage of p82 to p67.
      Since p67 is missing from ring-stage parasites (Howard et al., Am J Trop Med Hyg,
      1984;33:1055 59), the present results indicate there is a narrow time during
      which p67 may play a role in merozoite invasion of erythrocytes.

PMID- 9574916
TI  - Stable DNA transfection of the primitive protozoan pathogen Giardia lamblia.
AB  - We have developed a stable DNA transfection vector pRANneo for genetic
      manipulation of the primitive protozoan Giardia lamblia. pRANneo was constructed
      by replacing the protein coding region of a Giardia ran gene with a bacterial
      neomycin phosphotransferase gene (neo). This plasmid was electroporated into G.
      lamblia, and the transfectants were selected by G418. pRANneo replicated
      episomally to approximately 80 copies per G. lamblia trophozoite as demonstrated
      by dot hybridizations, Southern hybridizations and transformations of the DpnI
      treated plasmids into Escherichia coli. pRANneo/GDHluc was then constructed by
      incorporation of a luciferase expression system into pRANneo to persistently
      express firefly luciferase in G. lamblia under G418 selection. The NEO and
      luciferase proteins were detected in the transfected G. lamblia cells by Western
      blottings. The level of luciferase activity and the plasmid copy number
      correlated with the concentration of G418. Removal of G418 from the transfectant
      culture resulted in gradual loss of the plasmid and luciferase activity. The
      stable DNA transfection system should provide a valuable tool for genetic studies
      of G. lamblia.

PMID- 9574918
TI  - Molecular cloning and expression analysis of a Cryptosporidium parvum gene
      encoding a new member of the thrombospondin family.
AB  - The apicomplexan parasite Cryptosporidium parvum invades and multiplies primarily
      in the brush border cells of the intestinal mucosa causing in AIDS patients a
      severe diarrhoea that represents a significant contributing factor leading to
      death. Morphological analysis indicates that the invasion machinery of C. parvum
      is similar to the apical complex of other parasites of the phylum Apicomplexa. We
      provide here evidence indicating that C. parvum also shares with these parasites
      a molecule crucial for the invasion of host cells. We have cloned a 3894 bp-long
      C. parvum cDNA encoding a protein characterised by sequence and structural
      similarities with members of the thrombospondin (TSP) family previously described
      in apicomplexan parasites of the genera Toxoplasma, Eimeria and Plasmodium. This
      novel C. partum molecule, the TSP-related adhesive protein of Cryptosporidium-1
      (TRAP-C1), is encoded by a single copy gene containing no introns. TRAP-C1 is
      localised in the apical end of C. parvum sporozoites and is structurally related
      to the micronemal proteins MIC2 of Toxoplasma and Etp100 of Eimeria, which are
      involved in host-cell attachment and/or invasion. The identification of TRAP-C1
      sheds new light on the molecules possibly involved in the invasion process of
      intestinal cells by C. parvum. We have also analysed the sequence variation of
      TRAP-C1 among C. parvum isolates and in the closely related species C. wrairi.

PMID- 9574917
TI  - The Trypanosoma cruzi immunosuppressive factor (TIF) targets a lymphocyte
      activation event subsequent to increased intracellular calcium ion concentration
      and translocation of protein kinase C but previous to cyclin D2 and cdk4 mRNA
      accumulation.
AB  - Many immunosuppressive effects of Trypanosoma cruzi can be reproduced in vitro by
      a preparation consisting of molecules spontaneously released by this protozoan
      (termed trypanosomal immunosuppressive factor (TIF)). In this work, we attempted
      to establish whether TIF-induced inhibition of lymphoproliferation results from
      preventing lymphocyte activation or impairing a post-activation process. Although
      [3H]thymidine uptake and expression of CD25 by normal human T lymphocytes
      stimulated with a phorbol ester were markedly reduced by T. cruzi or TIF,
      translocation of cytosolic protein kinase C (PKC) to the cell membrane was not
      affected. Lymphoproliferation induced by ionomycin was also inhibited by T. cruzi
      or TIF but the typical elevation of intracellular calcium ions [Ca2+]i caused by
      this calcium ionophore was not altered. The increase in [Ca2+]i induced with anti
      CD3 antibody was also unaffected by TIF. TIF did not preclude lymphocytes
      stimulated with phytohemagglutinin from accumulating normal mRNA levels of NFAT1
      (also known as NFATp) and NFATc. NFAT1 and NFATc are components of the NFAT
      complex that controls transcription of genes coding for several cytokines and
      whose translocation to the nucleus is dependent upon PKC activation and increased
      [Ca2+]i. In contrast, the mRNA levels of cyclin D2 and cdk4, which form a
      holoenzyme complex known to regulate cell progression through the G1 phase, were
      markedly reduced by TIF. These results indicated that TIF did not inhibit
      lymphocyte activation leading to early secondary signaling but curtailed a
      mechanism controlling cell progression through G1 and necessary for reaching S
      phase.

PMID- 9574919
TI  - Identification of a developmentally regulated Trichinella spiralis protein that
      inhibits MyoD-specific protein: DNA complexes in vitro.
AB  - Development of the infective L1 larva of Trichinella spiralis occurs as an
      intracellular parasite of skeletal muscle and leads to the dedifferentiation of
      the host cell. A novel Trichinella gene, tsJ5, has been identified from a cDNA
      library screen for sequences encoding Trichinella proteins related to the
      myogenic bHLH factors. The tsJ5 gene is developmentally regulated, showing
      preferential expression in the infective muscle stage larva. The product of the
      tsJ5 gene is not a bHLH protein but represents a novel protein with properties in
      common with some myogenic repressors. A recombinant TsJ5 protein affects the
      formation of MyoD:DNA complexes in vitro.

PMID- 9574920
TI  - Implications of mycoplasma contamination in Plasmodium falciparum cultures and
      methods for its detection and eradication.

PMID- 9574921
TI  - Evidence for ADP-ribosylation and G protein in Theileria parva-transformed bovine
      lymphocytes.

PMID- 9574922
TI  - Merozoite surface protein 2 of Plasmodium reichenowi is a unique mosaic of
      Plasmodium falciparum allelic forms and species-specific elements.

PMID- 9574923
TI  - Expression and function of surface proteins in Trypanosoma brucei.

PMID- 9574924
TI  - The molecular phylogeny of trypanosomes: evidence for an early divergence of the
      Salivaria.
AB  - Chronic infections with trypanosomes dwelling extracellularly in the blood and
      tissues of their hosts are observed in all vertebrate classes. We present here a
      molecular phylogenetic reconstruction of trypanosome evolution based on
      nucleotide sequences of small subunit rRNA genes. The evolutionary tree suggests
      an ancient split into one branch containing all Salivarian trypanosomes and a
      branch containing all non-Salivarian lineages. The latter branch splits into a
      clade containing bird, reptilian and Stercorarian trypanosomes infecting mammals
      and a clade with a branch of fish trypanosomes and a branch of
      reptilian/amphibian lineages. The branching order of the non-Salivarian
      trypanosomes supports host-parasite cospeciation scenarios, but also suggests
      host switches, e.g. between bird and reptilian trypanosomes. The tree is
      discussed in relation to the modes of adaptation that allow trypanosomes to
      infect immunocompetent vertebrates. Most importantly, the early divergence of the
      Salivarian lineages suggests that the presence of a dense proteinaceous surface
      coat that is subject to antigenic variation is a unique invention of this group
      of parasites.

PMID- 9574925
TI  - Multiple mechanisms of immune evasion by African trypanosomes.
AB  - During infection of a mammalian host, African trypanosomes are in constant
      contact with the host's immune system. These protozoan parasites are infamous for
      their ability to evade the immune responses by periodically switching their major
      variant surface glycoprotein (VSG), a phenomenon called antigenic variation.
      Antigenic variation, however, is likely to be only one of several mechanisms
      enabling these organisms to thrive in the face of the immune defenses. The
      ability to grow in high levels of interferon-gamma (IFN-gamma) and to avoid
      complement-mediated destruction may also facilitate the parasite's survival. In
      this review we summarize (i) the activation of trypanosome genes for three
      different VSGs during antigenic variation, (ii) the secretion of a trypanosome
      protein that induces host CD8 T cells to produce IFN-gamma, and (iii) the
      evidence for trypanosome protein similar to a surface protease of Leishmania that
      plays a role in resistance to complement-mediated lysis.

PMID- 9574926
TI  - Control of VSG gene expression sites in Trypanosoma brucei.
AB  - Antigenic variation in African trypanosomes continues to be one of the most
      elaborate and intriguing strategies ever devised by a protozoan parasite to avoid
      complete destruction by the immune defense of its mammalian host. Here we review
      some of the recent advances in our understanding of this strategy, concentrating
      on (unpublished) work from our laboratory.

PMID- 9574927
TI  - Regulation of vsg expression site transcription and switching in Trypanosoma
      brucei.
AB  - Current understanding of expression-site transcription in Trypanosoma brucei, has
      been refined by recent results of promoter manipulations at vsg expression sites
      (ES) and examination of the behavior of ES promoters in ectopic locations both
      within the ES and at other loci. In summary, ES promoter sequences inserted into
      non-transcribed rRNA spacers are generally inactive, or have low activity, in
      bloodstream and procyclic forms. Some mechanism apparently operates to ensure
      full activation of a single ES in bloodstream-form trypanosomes and the
      inactivity of all ES promoters in procyclic forms. As previously shown, a rRNA
      promoter can replace an ES promoter. In bloodstream forms, the replacement rRNA
      promoter was down-regulated in a 'silent' ES but it was active in procyclic
      forms. In addition to manipulations of endogenous promoters, we have recently
      shown that, when an ES promoter is replaced by a T7 promoter, the T7 promoter is
      unregulated but transcription is attenuated before the vsg, and another ES
      switches on to maintain cell viability. However, T7 transcription is repressed in
      the context of core ES-promoter sequences in both stages, particularly in
      procyclic forms. These observations strongly argue that sequences in the vicinity
      of the ES core promoter play a role in ES control by nucleating critical events
      in silencing as well as in activation. Deletions of sequences surrounding the ES
      core promoter, in situ, did not affect its activity or regulation. In bloodstream
      forms, rRNA or ES promoters inserted adjacent to silent telomeres or to a non
      telomeric 'basic-copy' vsg were > 98% repressed. After transformation to
      procyclic forms, the sub-telomeric rRNA promoter regained about 10% of its
      maximal activity but the 'basic-copy' rRNA promoter was fully active. Similarly
      positioned ES promoters remained silent in procyclic forms. These results suggest
      that telomere-proximal or vsg-proximal sequences might mediate suppression of
      transcription via position-effects that could be sufficient to suppress the
      expression of chromosome-internal vsgs or telomeric metacyclic vsgs, in
      bloodstream-form trypanosomes. Recent experiments with T7 promoters indicate that
      sequences within the ES core promoter might be responsible for silencing ES
      promoters in procyclic forms. Precedents for regulatory mechanisms that modulate
      transcription over large chromatin domains are reviewed and possible models for
      ES regulation are presented.

PMID- 9574928
TI  - VSG gene control and infectivity strategy of metacyclic stage Trypanosoma brucei.
AB  - As the metacyclic trypanosome stage develops in the tsetse fly salivary glands,
      it initiates expression of variant surface glycoproteins (VSGs) and does so by
      each cell activating, at random, one from a small subset of metacyclic VSG (M
      VSG) genes. Whereas differential activation of individual VSG genes in the
      bloodstream occurs as a function of time, to evade waves of antibody, it is
      believed that the aim in the metacyclic stage is simultaneously to generate
      population diversity. M-VSG genes are activated in their telomeric loci and
      belong to monocistronic transcription units, unlike all other known trypanosome
      protein-coding genes, which appear to be transcribed polycistronically. The
      promoters of these metacyclic expression sites (M-ESs) have the unique property,
      in this organism, of being switched on and off in a life-cycle stage specific
      pattern. We have found that the 1.22 M-ES promoter is regulated according to life
      cycle stage, differential control being exerted through different elements of the
      promoter and under the influence of its genomic locus. We have characterized in
      detail the telomeres containing the 1.22 and 1.61 M-ESs. Upstream of the M-ES is
      a possibly haploid, non-transcribed region with some degenerate sequences
      homologous with expression site associated genes (ESAGs) that occur in
      bloodstream VSG expression sites. Further upstream (respectively, 22 and 13 kb
      upstream of the 1.22 and 1.61 VSG genes) are alpha-amanitin sensitive
      transcription units that may be polycistrons and are transcribed in all examined
      life cycle stages. They contain a number of genes. The differences between
      metacyclic and bloodstream ESs may have important consequences for life cycle
      regulation, genetic stability, phenotype complexity and adaptability of the
      metacyclic stage as it infects different host species.

PMID- 9574929
TI  - Controls of the expression of the Vsg in Trypanosoma brucei.
AB  - We present an overview of the regulation of vsg expression, focusing on
      initiation and elongation of transcription as well as processing and
      stabilization of the transcripts. We propose a model where common factors are
      involved in the reverse controls of the genes for the two main stage-specific
      antigens, the Vsg and procyclin: a cross-talk between the two transcription units
      would allow a fast rerouting of limiting factors at differentiation, thereby
      allowing the expression of only one type of antigen at a time. A similar
      mechanism would ensure that only one vsg ES is fully expressed at a time in
      bloodstream forms.

PMID- 9574930
TI  - Unravelling the procyclin coat of Trypanosoma brucei.

PMID- 9574931
TI  - PARP gene expression: control at many levels.

PMID- 9574932
TI  - The glycosylation of the variant surface glycoproteins and procyclic acidic
      repetitive proteins of Trypanosoma brucei.
AB  - Trypanosoma brucei, in common with the other African trypanosomes, exhibits
      unusual cell-surface molecular architecture. The bloodstream form of the parasite
      is coated with a continuous layer of approximately five million variant surface
      glycoprotein (VSG) dimers that provide the parasite with a macromolecular
      diffusion barrier to guard against lysis by the alternative complement pathway.
      The procyclic form of the parasite has a more diffuse cell-surface coat made up
      of approximately 2.5 million copies of procyclic acidic repetitive protein
      (PARP). Within the VSG and PARP coats exist lower-abundance surface glycoproteins
      such as receptors and nutrient transporters. Both the VSG molecules and the PARP
      molecules are attached to the membrane via glycosylphosphatidylinositol (GPI)
      membrane anchors and the VSGs and one form of PARP are N-glycosylated. In this
      article, the structures of the N-glycans and the GPI anchors of T. brucei VSGs
      and PARPs are reviewed and simple models of the surfaces of bloodstream and
      procyclic trypomastigotes are presented.

PMID- 9574934
TI  - Both IgM and IgG anti-VSG antibodies initiate a cycle of aggregation
      disaggregation of bloodstream forms of Trypanosoma brucei without damage to the
      parasite.
AB  - Bloodstream forms of Trypanosoma brucei, when aggregated in the presence of
      either acute immune plasma, acute immune serum, purified IgM anti-VSG antibodies
      or purified IgG anti-VSG antibodies, subsequently disaggregated with a t1/2 for
      disaggregation of 15 min at 37 degrees C as long as the trypanosomes were
      metabolically active at the beginning of the experiment and maintained during the
      experiment in a suitable supporting medium. The t1/2 for disaggregation was found
      to be directly dependent upon temperature and inversely proportional to the
      antibody concentration. The trypanosomes were always motile and metabolically
      active during aggregation and after disaggregation and were fully infective for a
      mammalian host following disaggregation as well as able to grow and divide
      normally during axenic culture. The disaggregation was strictly energy dependent
      and was inhibited when intracellular ATP levels were reduced by salicylhydroxamic
      acid or following addition of oligomycin while respiring glucose. In addition the
      process of disaggregation was dependent upon normal endosomal activity as
      evidenced by its sensitivity to a wide variety of inhibitors of various endosomal
      functions. Disaggregation was not due to separation of immunoglobulin chains by
      either disulphide reduction or disulphide exchange reactions and gross
      proteolytic cleavage of the immunoglobulins attached to the surface of the
      parasite was not detected. In addition, gross cleavage or release of the VSG from
      the surface of the cell did not occur during disaggregation but proteolytic
      cleavage of a small proportion of either the VSG or the immunoglobulins could not
      be eliminated from consideration. Finally the mechanism of disaggregation was
      found to be a regulated process, independent of Ca2+ movements but dependent upon
      the activity of protein kinase C or related kinases and inhibited by the activity
      of protein kinase A as evidenced by the effects of a panel of inhibitors and cAMP
      analogues on the process of disaggregation. The mechanism of disaggregation
      displayed by trypanosomes aggregated by anti-VSG antibody is proposed to form
      part of the parasite's defence against the host immune system and functions to
      aid survival of trypanosomes in the presence of antibody in the host prior to the
      occurrence of a VSG switching event.

PMID- 9574933
TI  - The properties and function of the glycosylphosphatidylinositol-phospholipase C
      in Trypanosoma brucei.
AB  - The purpose of this review is to consider recent results obtained concerning the
      properties and function of the glycosylphosphatidylinositol-phospholipase C (GPI
      PLC) in Trypanosoma brucei. A mutagenesis study that provides evidence that the
      GPI-PLC is more closely related to bacterial PI-PLCs than previously realised is
      described. The variant specific glycoprotein (VSG), which dominates the surface
      of the mammalian stages of the trypanosome, is almost certainly the major
      substrate of the GPI-PLC. The hydrolysis of the GPI-anchor of the VSG under
      stress conditions and hypotonic lysis is well established. To investigate whether
      this hydrolysis of the GPI-anchor plays any role during the life cycle a GPI-PLC
      null mutant has been made. The phenotype indicates that the gene is non
      essential, but its absence alters the course of infection in mice.

PMID- 9574935
TI  - Trypanosome glucose transporters.

PMID- 9574936
TI  - Is lichen planus really premalignant?

PMID- 9574937
TI  - Malignant transformation of leukoplakia.

PMID- 9574938
TI  - Mercury poisoning and acrodynia.

PMID- 9574939
TI  - Calcium pyrophosphate dihydrate crystal deposition disease of the
      temporomandibular joint.

PMID- 9574940
TI  - Obstructive sleep apnea: a review of the pathophysiology and surgical management.

PMID- 9574941
TI  - Presence of impacted teeth as a determining factor of unfavorable splits in 1256
      sagittal-split osteotomies.
AB  - OBJECTIVES: The purpose of this study was to determine the incidence of
      unfavorable mandibular fracture in sagittal-split osteotomies in the presence or
      absence of impacted third molar teeth. STUDY DESIGN: This retrospective study
      evaluated 1256 mandibular sagittal-split osteotomies in two groups of patients:
      Group I had impacted third molar teeth removed during sagittal-split osteotomy;
      in Group II, the third molar teeth had been removed at least 6 months before the
      sagittal-split osteotomy. Statistical testing consisted of chi-square analysis of
      contingency table for p < 0.05. RESULTS: In 1256 mandibular sagittal-split
      osteotomies there were 24 (1.9%) with unfavorable fractures. Five of 24 occurred
      when third molar teeth were removed at the time of osteotomy and 19 of 24
      mandibular fractures occurred when no impacted third molar tooth was present at
      the time of osteotomy. However, no significant difference was demonstrated
      between the groups. CONCLUSION: The result of this study suggests that mandibular
      fractures may occur with greater frequency when the impacted third molar teeth
      have been removed at least 6 months before sagittal-split osteotomy as compared
      with that when third molar teeth are removed concomitant with sagittal-split
      osteotomy.

PMID- 9574942
TI  - Is short-term neurosensory testing after removal of mandibular third molars
      efficacious?
AB  - OBJECTIVE: The purpose of this study was the validation of two-point
      discrimination, Semmes-Weinstein, and pinprick tests of possible sensory
      disturbance of the inferior alveolar nerve after the surgical removal of lower
      wisdom teeth. STUDY DESIGN: Forty-two patients who had undergone elective
      unilateral lower wisdom tooth removal and 30 control subjects were given two
      point discrimination, Semmes-Weinstein, and pinprick tests bilaterally in the
      dermatome of the mental nerve. Test results were compared to the patients
      subjective experiences of sensory disturbance. Statistical analysis was done with
      multivariate analysis of variance. RESULTS: Untreated sides in patients and test
      sides in control subjects agreed well for all tests. Five of the 42 patients
      mentioned sensory disturbance, which was confirmed objectively in 3 (by pinprick
      and two-point discrimination tests). Testing revealed that 16 of the 42 patients
      had abnormal pinprick and two-point discrimination tests without subjective
      sensory disturbance. No abnormal values were found for Semmes-Weinstein tests in
      any of the patients. Multivariate analysis of variance identified a univariately
      significant effect of the two-point discrimination test (p = 0.027); all other
      interactions were multivariately insignificant. CONCLUSION: The value of
      neurosensory testing after third molar removal is limited because of
      inconsistency between objective test results and subjective findings.

PMID- 9574943
TI  - Three-dimensional computed tomography evaluation of postsurgical condylar
      displacement after mandibular osteotomy.
AB  - OBJECTIVE: The purpose of this study was to examine both condylar displacement of
      the temporomandibular joint after sagittal split ramus osteotomy with rigid
      osteosynthesis and intraoral vertical ramus osteotomy without osteosynthesis in
      patients with mandibular prognathism by means of three-dimensional computed
      tomography. STUDY DESIGN: In this pilot study, five patients treated with
      sagittal split ramus osteotomy and 5 patients treated with intraoral vertical
      ramus osteotomy were evaluated. A technique to superimpose a postoperative three
      dimensional computed tomography image on its corresponding preoperative image was
      designed. Postoperative condylar displacement, rotation, and tilting were
      measured in three-dimensional computed tomography images. RESULTS: Within 3 to 6
      months after surgery, changes in the inclination of the condylar axes were
      distinctly seen, although changes in the position of the condyles within the
      joints were minimal. In particular, outward rotation of the condylar long axes
      after intraoral vertical ramus osteotomy was a frequent finding. CONCLUSIONS: The
      three-dimensional computed tomography superimposition technique was a practical
      method of evaluating postsurgical condylar displacement after mandibular
      osteotomy.

PMID- 9574944
TI  - Evaluation of disk capture with a splint repositioning appliance: clinical and
      critical assessment with MR imaging.
AB  - OBJECTIVE: The purpose of this study was to evaluate disk repositioning
      clinically and through use of magnetic resonance imaging after the insertion of a
      disk repositioning appliance. STUDY DESIGN: Seventy-four patients with 82
      temporomandibular joints showing middle to late opening movement click and
      closing movement click near maximum intercuspation were treated with a mandibular
      full-coverage repositioning splint. These joints were assessed clinically and by
      means of magnetic resonance imaging for disk recapture. RESULTS: According to
      clinical assessment, 75.6% (62/82) of the joints were treated successfully; no
      click was observed from the splinted mandibular position. When compared with the
      results of magnetic resonance imaging assessment, clinical assessment showed an
      accuracy rate of 91.5%, although the incidence of the false negatives was high
      (40%). CONCLUSIONS: The results of this study showed that about 70% of reducing
      displaced disks were captured with use of the disk repositioning appliance. And
      it was also suggested that magnetic resonance imaging is helpful to evaluate disk
      repositioning therapy.

PMID- 9574946
TI  - Obstructive sleep apnea: oral appliance therapy and severity of condition.
AB  - OBJECTIVE: The purpose of this study was to determine whether an oral appliance
      can effectively treat severe obstructive sleep apnea. DESIGN: The study was
      conducted at a tertiary care military facility with an accredited sleep
      laboratory. Results of the treatment of the first 25 patients with obstructive
      sleep apnea referred for oral appliance therapy were retrospectively analyzed.
      Each patient received a mandibular advancement appliance and underwent
      polysomnography 2 weeks after delivery of the appliance. Patients were divided
      into two groups: those with slight-to-mild obstructive sleep apnea who had a
      respiratory disturbance index less than 21, and those with more severe disease.
      Treatment was considered to be successful if the posttreatment respiratory
      disturbance index was less than 5. RESULTS: Nine (90%) of the 10 patients with
      slight-to-moderate disease were successfully managed with the oral appliance. Of
      the 15 patients in the moderate-to-severe group, 9 (60%) were successfully
      managed. CONCLUSION: Oral appliances have commonly been recommended only for mild
      obstructive sleep apnea. This study indicates that they may also have a role to
      play in selected cases in which the condition is more severe. There is a paucity
      of information about long-term success. This short-term (2-week) study should be
      followed by others evaluating the effect over longer periods.

PMID- 9574945
TI  - Perioperative use of 0.12% chlorhexidine gluconate for the prevention of alveolar
      osteitis: efficacy and risk factor analysis.
AB  - OBJECTIVES: The purposes of this study were to evaluate the use of 0.12%
      chlorhexidine gluconate as a prophylactic therapy for the prevention of alveolar
      osteitis and to further examine subject-based risk factors associated with
      alveolar osteitis. STUDY DESIGN: The trial was a randomized, double-blind,
      placebo-controlled, parallel-group study conducted among 279 subjects, each of
      whom required oral surgery for the removal of a minimum of one impacted
      mandibular third molar. Subjects were instructed to rinse twice daily with 15 ml
      of chlorhexidine or placebo mouthrinse for 30 seconds for 1 week before and 1
      week after the surgical extractions. This regimen included a supervised
      presurgical rinse. Alveolar osteitis diagnosis was based on the subjective
      finding of increasing postoperative pain at the surgical site that was not
      relieved with mild analgesics, supported by clinical evidence of one or more of
      the following: loss of blood clot, necrosis of blood clot, and exposed alveolar
      bone. RESULTS: In comparison with use of the placebo mouthrinse, prophylactic use
      of the chlorhexidine mouthrinse resulted in statistically significant (p < 0.05)
      reductions in the incidence of alveolar osteitis. With chlorhexidine therapy, the
      subject- and extraction-based incidences of alveolar osteitis in the evaluable
      subset (271 subjects) were reduced, relative to placebo, by 38% and 44%,
      respectively. The corresponding odds ratios that describe the increased odds of
      experiencing alveolar osteitis in the placebo group were 1.87 and 2.05 for
      subject- and extraction-based analyses, respectively. In comparison with nonuse
      of oral contraceptives, the use of oral contraceptives in female subjects was
      related to a statistically significant increase in the incidence of alveolar
      osteitis (odds ratio = 1.92, p = 0.035). Relative to male subjects, the observed
      incidence of alveolar osteitis for female subjects not using oral contraceptives
      was not statistically significant (odds ratio = 1.18, p = 0.64). Smoking did not
      increase the incidence of alveolar osteitis relative to not smoking (odds ratio =
      1.20, p = 0.33). CONCLUSIONS: These data confirm that the prophylactic use of
      0.12% chlorhexidine gluconate mouthrinse results in a significant reduction in
      the incidence of alveolar osteitis after the extraction of impacted mandibular
      third molars. In addition, oral contraceptive use in females was confirmed to be
      a risk factor for the development of alveolar osteitis.

PMID- 9574947
TI  - Permeation of 17beta-estradiol through human vaginal and buccal mucosa.
AB  - Because of the relative scarcity of fresh human oral mucosa specimens for
      permeability studies, we investigated the use of human vaginal mucosa as a model
      of the former. In a previous study we demonstrated the comparable diffusion rate
      of water across human vaginal and buccal mucosa and proposed the use of the
      former as a suitable model of the latter for in vitro drug permeability studies.
      To further evaluate the human vaginal/buccal mucosa model, we decided to compare
      these two tissues with respect to their permeability to 17beta-estradiol.
      Clinically healthy human vaginal and buccal mucosa specimens were obtained during
      vaginal hysterectomies and different oral surgical procedures. The permeability
      of each tissue specimen to 17beta-estradiol was determined through the use of a
      continuous flow-through diffusion system. Specimens were examined histologically
      before and after experiments. Mean flux values for 17beta-estradiol across human
      buccal mucosa tended to be slightly higher than those observed for vaginal
      tissue, but no statistically significant differences could be demonstrated. The
      results from this study further support our hypothesis that human vaginal mucosa
      may be a suitable model of human buccal mucosa for in vitro drug permeability
      studies.

PMID- 9574948
TI  - Herpes B virus infection.
AB  - Herpes B virus (B virus) infection is common in macaques. Primary infection of B
      virus in primates is similar to herpes simplex virus 1 infection in human beings,
      but B virus generally produces only mild localized lesions in its natural host.
      In human beings, however, B virus can cause severe infection that may lead to
      death from encephalitis. Contact with monkey saliva, tissues, or tissue fluids is
      the most commonly reported route of transmission of B virus; a single case of
      person-to-person transmission has been reported. Airborne transmission is
      postulated to have occurred as a result of clinical circumstances in two reported
      cases, but there is no strong evidence to support the hypothesis of aerosol
      infection. Because B virus infection in human beings is often fatal, awareness of
      the risk of B virus infection should be emphasized. Although B virus infection in
      human beings is rare, it is an occupational health risk in exposed health care
      workers and laboratory personnel. This review of the literature of B virus
      infection includes case reports and a discussion of the nature of the B virus,
      characteristics of B virus infection in primates and human beings, the treatment
      of human infection, and the implications for dental health care providers. This
      report also serves as an introduction of the disease to the dental literature.

PMID- 9574949
TI  - Fibrosarcoma misdiagnosed as a temporomandibular disorder: a cautionary tale.
AB  - Because of the abundance of articles on temporomandibular disorders in the dental
      literature, other sources of facial pain and mandibular dysfunction do not
      receive adequate diagnostic attention. The case report in this article describes
      a female patient who appeared for treatment with symptoms and signs similar to
      those encountered in subsets of temporomandibular disorders. Her condition was
      misdiagnosed, and she was treated for a temporomandibular disorder over an
      extended period before the correct diagnosis of high-grade pharyngeal
      fibrosarcoma was established. Once diagnosed, the tumor was treated aggressively
      with preoperative and postoperative combinations of chemotherapy and radiation.
      Despite the intensive therapy, the patient died. This case should remind the
      clinician that nonmusculoskeletal sources of persistent facial pain and
      dysfunction, including tumors, may be masked by or mimic temporomandibular
      disorders. If therapy does not produce the expected outcome, the diagnosis should
      be reexamined.

PMID- 9574950
TI  - Dental changes in hypervitaminosis D.
AB  - Vitamin D is required for the normal development of teeth and bones. When there
      is excess vitamin D, systemic and dental changes may occur. This is a case report
      of a girl who experienced hypercalcemia secondary to excess vitamin D derived
      from the consumption of milk that was incorrectly fortified. The changes in the
      permanent dentition to date are enamel hypoplasia and focal pulp calcification.
      These changes correspond to the timing of the toxemia caused by hypervitaminosis
      D.

PMID- 9574951
TI  - Immunochemical and biochemical characteristics of enamel proteins in
      hypocalcified amelogenesis imperfecta.
AB  - Amelogenesis imperfecta is a hereditary disease of the enamel that is
      unassociated with generalized defects. Cases of the condition are clinically
      classified into three groups: hypoplastic, hypomaturation, and hypocalcified. In
      this study, soluble protein fractions of the enamel from three patients with
      hypocalcified amelogenesis imperfecta were examined through the use of
      immunochemical and biochemical techniques. In immunochemical analyses done with a
      polyclonal anti-amelogenin antibody, all samples from enamel in which there was
      amelogenesis imperfecta were found to contain considerable amounts of amelogenin
      peptides. When an enamel sample from one patient was examined by Western-blot
      transfer and immunobinding analysis, the amelogenin fraction was found to consist
      of a 26-kDa molecule thought to be normally present in the outer layer of
      secretory-stage enamel. This enamel was also found to contain albumin as one of
      the major constituents of the protein fraction. These results suggest that
      hypocalcified amelogenesis imperfecta may in part be caused by a disturbance in
      matrix protein degradation during the maturation phase.

PMID- 9574952
TI  - Tubulopapillary hidradenoma-like tumor of the mandible: clinicopathologic and
      immunohistochemical features.
AB  - Tubulopapillary hidradenoma is a benign sweat gland tumor that appears as a well
      defined, superficially located dermal nodule. It combines ductal as well as
      apocrine and eccrine glandular differentiation. Microscopically, the tumor is
      composed of tubular structures that characteristically show intraluminal non
      villous papillary projections and a peripheral myoepithelial cell layer. A tumor
      that is histologically and immunohistochemically identical to tubulopapillary
      hidradenoma occurred in the mandible of a 73-year-old man and resulted in
      considerable diagnostic difficulty. The neoplasm developed in a mandibular cyst
      and recurred 5 years after initial enucleation. This is the first report of a
      central (intraosseous) sweat gland adenoma of the mandible. The differential
      diagnosis and possible histogenesis are discussed.

PMID- 9574953
TI  - Cytokeratin expression in squamous cell carcinoma of the lung and oral cavity: an
      immunohistochemical study with possible clinical relevance.
AB  - OBJECTIVE: Serologic identification of the fragment of cytokeratin 19 known as
      CYFRA 21-1 has been used for early detection of squamous cell carcinoma of the
      lung. The sensitivity of the CYFRA 21-1 assay in detecting oral cancers is lower
      than that in detecting lung cancers. To clarify the reason for this, we compared
      the cytokeratin expression in these cancers, with special reference to
      cytokeratin 19. STUDY DESIGN: Oral squamous cell carcinomas and lung squamous
      cell carcinomas were immunostained with cytokeratin 19, cytokeratin 10, and
      cytokeratin 13 antibodies. Staining intensity was scored on a graduated scale
      from 0 to 4. RESULTS: With respect to cytokeratin 19, the stainings of all lung
      cancers were scored as 4, which indicates a greater expression of cytokeratin 19
      than is seen in oral cancers (p < 0.01). With an average cytokeratin 19 staining
      score of 1.67, oral cancers ranked lowest among the antibodies. Squamous cell
      carcinomas of the maxillary sinus arising from pseudostratified ciliated
      epithelium were highly expressive of cytokeratin 19. A marker for keratinizing
      cells (cytokeratin 10) and a marker for squamous cells (cytokeratin 13) were
      expressed more frequently and intensely in oral cancers (p < 0.01) than in lung
      cancers (p = 0.019). CONCLUSIONS: From the viewpoint of immunohistochemistry,
      cytokeratin 19 was found to be a tumor marker with low specificity and
      sensitivity in oral cancers. The staining results suggested that poor expression
      of cytokeratin 19 by oral squamous cell carcinoma may result in a low serum value
      of CYFRA 21-1 in patients with this condition.

PMID- 9574954
TI  - The application of toluidine blue as a diagnostic adjunct in the detection of
      epithelial dysplasia.
AB  - The detection of premalignant lesions of the oral mucosa allows for treatment
      that may be sufficiently early to prevent their progression to invasive
      carcinoma. Although a number of techniques for supplementing clinical examination
      have been described, on the whole they rely on laboratory-based investigations
      with variable false-negative rates. Toluidine blue vital staining, on the other
      hand, has been advocated as a simple, inexpensive, and sensitive chairside test.
      Most of the clinical series investigating its efficacy, however, have relied on
      clinically abnormal mucosa or tissue that stained. For the purpose of quantifying
      the true sensitivity of toluidine blue, the present study involved the
      examination of clinically normal mucosa as well as abnormal tissue and compared
      it with the presence or absence of staining. With this technique the false
      negative rates of 42% and 58% obtained for carcinoma-in-situ and mild-to-moderate
      dysplasia, respectively, suggest restricting the use of vital staining to
      selective cases.

PMID- 9574955
TI  - Primary squamous cell carcinoma of accessory parotid gland duct epithelium:
      report of a case.
AB  - A rare case of primary squamous cell carcinoma surrounding Stensen's duct in a 75
      year-old man is presented. The tumor was a relatively well-defined, hard,
      subcutaneous mass, measuring 18 x 14 x 9 mm and situated in the right cheek.
      Microscopic examination of an excisional biopsy specimen revealed tumor cells
      showing squamous differentiation, a papillary growth pattern, and ductal
      structures with comedo necrosis. Immunohistochemical studies showed positive
      reactivity for KL-1 (cytokeratin, monoclonal), epithelial membrane antigen, and
      carcinoembryonic antigen in some tumor cells. The origin of the tumor was thought
      to be the accessory parotid gland duct epithelium.

PMID- 9574956
TI  - The odontogenic keratocyst: a potential endodontic misdiagnosis.
AB  - Odontogenic keratocysts manifest themselves as radiolucencies that can appear
      anywhere in the maxilla or mandible, including periradicular areas; they may thus
      masquerade as lesions of endodontic origin. This retrospective study examined 239
      odontogenic keratocysts received by the Oral Pathology Laboratory at Temple
      University School of Medicine over a 3-year period. Twenty-one (9%) of the cysts
      received were located periradicularly; of these 21, 12 (57%) were associated with
      nonvital or endodontically treated teeth and thus mimicked lesions of endodontic
      origin. Because of its aggressive nature and tendency to recur, the periradicular
      odontogenic keratocyst should be included in the differential diagnosis of
      lesions that are refractory to endodontic treatment.

PMID- 9574957
TI  - Position of the mental foramen in a North American, white population.
AB  - Knowledge of the position of the mental foramen is important both when
      administering regional anesthesia and performing periapical surgery in the
      mandible. Although it is often possible to identify the mental foramen by
      palpation and radiographically, knowing the normal range of possible locations is
      essential. Standard anatomic texts have data collected from dried skulls, but
      often of unknown origin or from an ethnic group that does not represent the North
      American population. OBJECTIVES: This study identified the position of the mental
      foramen in a more representative sample of the North American population. Ethnic
      and gender differences were also investigated and the symmetry of location within
      individuals analyzed. STUDY DESIGN: Regional dissections of 105 human cadavers
      were carried out to identify the normal range of position of the mental foramen.
      The vertical and horizontal position was recorded with the two adjacent teeth
      used as references. If the two adjacent teeth were not present the foramen was
      not included in the study. RESULTS: The results indicated that the mental foramen
      was, on average, between the premolars, therefore not statistically different
      from previous studies. However, there appears to be a greater range than
      generally reported, which is of considerable clinical significance. Examples of
      dissections of unusually positioned mental foramina are given.

PMID- 9574958
TI  - Intracoronal radiolucency in an incompletely erupted permanent molar with a
      diagnosis of pericoronitis: importance of radiographic examination.
AB  - Because of clinical signs and symptoms, a diagnosis of pericoronitis in a
      partially erupted, partially impacted first molar was made. A more thorough
      diagnosis was made with the help of a periapical radiograph that showed caries
      and thus revealed an irreversible pulpitis. Appropriate treatment was the result.

PMID- 9574959
TI  - Quantitative digital subtraction radiography for the determination of small
      changes in bone thickness: an in vitro study.
AB  - OBJECTIVE: The objective of this study was to determine the ability of
      quantitative digital subtraction radiography to detect small changes in bone
      thickness adjacent to tooth roots. STUDY DESIGN: A series of cortical or
      cancellous bone slices with a 50 microm-stepwise increasing thickness were
      attached to 4 porcine mandible sections covering buccal and interproximal
      "defect" regions. Standardized radiographs were quantitatively evaluated for
      radiographic density changes with the use of digital subtraction radiography.
      Furthermore, all radiographs were conventionally evaluated by 10 clinicians. The
      Wilcoxon signed-rank test and the Mann-Whitney U test were used for statistical
      analysis (alpha = 0.05). RESULTS: A high linear correlation was found between the
      actual thickness of bone slices and radiographic density changes (cortical bone:
      r2 = 0.89 to 0.99; cancellous bone r2 = 0.61 to 0.86, p < or = 0.001). A certain
      increase in bone thickness caused a 3 times higher increase in radiographic
      density for cortical bone than for cancellous bone (p < or = 0.05). The detection
      limits of digital subtraction radiography were 200 microm for cortical and 500
      microm for cancellous bone, whereas the detection limits of conventional
      radiography were 600 microm and 2850 microm, respectively. CONCLUSIONS: This in
      vitro study demonstrated a very high correlation between the objective,
      quantitative assessment of subtle changes in alveolar bone by digital subtraction
      radiography and the true changes in bone thickness.

PMID- 9574960
TI  - Semiautomated image registration for digital subtraction radiography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the semiautomatic alignment
      and correction of affine geometric discrepancies for digital subtraction
      radiography. STUDY DESIGN: Algorithms were tested in vitro to determine their
      ability to semiautomatically select reference points on a second image based on
      points selected on a first (reference) image. A preserved human mandible was
      imaged with and without bone-equivalent material chips at varying degrees of
      angulation. Each chip had a mass of less than 10 mg and was no more than 0.3 mm
      thick. High levels of specificity and sensitivity for chip detection were
      achieved with 6 degrees of angular discrepancy or less. The algorithms were then
      applied to radiographs from six human subjects through use of the bone-chip
      validation model. RESULTS: Sensitivity was 89% and 100% for the three-point and
      four-point affine warp algorithms, respectively. Specificity for both algorithms
      was 100%. CONCLUSIONS: The data indicate that semiautomated alignment algorithms
      may enhance the efficacy of digital subtraction radiography while maintaining
      diagnostic efficacy in clinical trials.

PMID- 9574961
TI  - Radiographic image of the hard palate and nasal fossa floor in panoramic
      radiography.
AB  - OBJECTIVE: The aim of this investigation was to report on the radiographic
      interpretation of the hard palate and nasal fossa floor in panoramic radiographs
      by studying different skulls, x-ray machines, and head positions in relationship
      to the Frankfort plane before and after ostectomy. STUDY DESIGN: Twenty dry human
      skulls were radiographed with three different panoramic x-ray machines in three
      different positions. Three of the skulls were submitted to different ostectomies.
      RESULTS: Multiple images of the hard palate and nasal fossa floor were present in
      96.12% of the radiographs. Single images (3.88%) occurred only in the "chin up"
      position. CONCLUSIONS: The lower image represents the nasal fossa floor,
      especially its lateral and anterior limits. The upper images are double real
      images mainly formed by the junction of the nasal septum with the nasal fossa
      floor and possibly by posterior parts of the hard palate and nasal fossa floor.
      All images overlap in the "chin up" position becoming a single image. The most
      common shape of the anatomic landmark was wide angle "W" (58.33%). Other shapes
      present in positions "chin up" and "chin down" indicate patient positioning
      errors. The x-ray machines did not influence the results.

PMID- 9574962
TI  - A perceptibility curve comparison of Ultra-speed and Ektaspeed Plus films.
AB  - OBJECTIVE: The purpose of this study was to evaluate the subjectively assessed
      contrast difference between Kodak's Ultra-speed and Ektaspeed Plus dental
      radiography films (Eastman Kodak, Rochester, N.Y.) through the use of
      perceptibility curves. DESIGN: Four series of 22 radiographs were exposed at 70
      and 90 kVp with each film type by means of a Gendex 1000 dental radiography unit
      (Gendex Corp., Milwaukee, Wis.) for times ranging from 0.05 to 5 seconds at 10
      ma. The test object consisted of a 7-mm-thick rectangular aluminum block with 10
      circular depth cuts, each 2 mm in diameter, which created wells varying in depth
      from 50 to 500 microns. The corresponding films were processed concurrently (for
      4.5 minutes) in total darkness with fresh Kodak Readymatic solutions (Eastman
      Kodak) held at a constant temperature of 28 degrees C. The resulting radiographs
      were viewed in a predetermined random order under ideal conditions by 10
      dentists. The evaluators recorded the maximum number of perceptible images on
      each film. A pair of perceptibility curves were generated at 70 and 90 kVp by
      plotting the log relative exposure versus the mean number of perceptible images.
      RESULTS: There was no statistical difference between the two film types with
      respect to the mean number of perceptible images, as analyzed by Wilcoxon's
      signed rank test (p = 0.22; p = 0.44). CONCLUSIONS: There is no subjectively
      assessed contrast difference between Kodak s Ultra-speed and Ektaspeed Plus films
      at 70 and 90 kVp.

PMID- 9574963
TI  - Proceedings and abstracts of the Manchester meeting of the Society for Research
      into Hydrocephalus and Spina Bifida, 1997.

PMID- 9574964
TI  - [Lectures of the annual meeting of the German Society of Biomedical Techniques.
      Munich, 22-24 October 1997].

PMID- 9574965
TI  - A penalized likelihood approach for arbitrarily censored and truncated data:
      application to age-specific incidence of dementia.
AB  - The Cos model is the model of choice when analyzing survival data presenting only
      right censoring and left truncation. There is a need for methods that can
      accommodate more complex observation schemes involving general censoring and
      truncation. In addition, it is important in many epidemiological applications to
      have a smooth estimate of the hazard function. We show that the penalized
      likelihood approach gives a solution to these problems. The solution of the
      maximum of the penalized likelihood is approximated on a basis of splines. The
      smoothing parameter is estimated using approximate cross-validation; confidence
      bands can be given. A simulation study shows that this approach gives better
      results than the smoothed Nelson-Aalen estimator. We apply this method to the
      analysis of data from a large cohort study on cerebral aging. The age-specific
      incidence of dementia is estimated and risk factors of dementia studied.

PMID- 9574966
TI  - Survival analysis with uncertain endpoints.
AB  - In some survival analysis applications, the endpoint of interest has a degree of
      uncertainty associated with it. These events are typically classified by the
      investigator or by an endpoint committee as true or false according to some
      decision rule, and the analysis proceeds using only the true endpoints. This
      procedure has two drawbacks: The cut point for the decision rule is somewhat
      arbitrary, and the information contained in the level of certainty is lost. This
      paper introduces a modification of the Cox regression model that allows all
      potential endpoints to be included in the analysis along with the level of
      certainty of each. Simulation results show this procedure to considerably
      increase the power of the standard procedure in a wide range of situations.

PMID- 9574967
TI  - Pattern formation in a generalized chemotactic model.
AB  - Many models have been proposed for spatial pattern formation in embryology and
      analyzed for the standard case of zero-flux boundary conditions. However,
      relatively little attention has been paid to the role of boundary conditions on
      the form of the final pattern. Here we investigate numerically, the effect of
      nonstandard boundary conditions on a model pattern generator, which we choose to
      be of a cell-chemotactic type. We specifically focus on the role of boundary
      conditions and the effects of scale and aspect ratio, and study the
      spatiotemporal dynamics of pattern formation. We illustrate the properties of the
      model by application to the spatiotemporal sequence of skeletal development.

PMID- 9574968
TI  - A mathematical model for fibroblast and collagen orientation.
AB  - Due to the increasing importance of the extracellular matrix in many biological
      problems, in this paper we develop a model for fibroblast and collagen
      orientation with the ultimate objective of understanding how fibroblasts form and
      remodel the extracellular matrix, in particular its collagen component. The model
      uses integrodifferential equations to describe the interaction between the cells
      and fibers at a point in space with various orientations. The equations are
      studied both analytically and numerically to discover different types of
      solutions and their behavior. In particular we examine solutions where all the
      fibroblasts and collagen have discrete orientations, a localized continuum of
      orientations and a continuous distribution of orientations with several maxima.
      The effect of altering the parameters in the system is explored, including the
      angular diffusion coefficient for the fibroblasts, as well as the strength and
      range of the interaction between fibroblasts and collagen. We find the initial
      conditions and the range of influence between the collagen and the fibroblasts
      are the two factors which determine the behavior of the solutions. The
      implications of this for wound healing and cancer are discussed including the
      conclusion that the major factor in determining the degree of scarring is the
      initial deposition of collagen.

PMID- 9574969
TI  - A stochastic two-phase growth model.
AB  - This article proposes a stochastic growth model that starts as a Yule process and
      is subsequently joined with a Prendiville process when the population attains
      certain prescribed critical size. In other words, the model assumes a exponential
      growth in an early stage and logistic growth later on to reflect growth
      retardation caused by overcrowding. In the case that the population starts with a
      single unit, closed form expressions are given for the distribution of the
      population size and for the mean and variance functions of the process. Numerical
      solutions are briefly discussed for the process that starts with more than one
      unit.

PMID- 9574970
TI  - A continuum mechanics approach to determining the cellular velocity field with a
      wool follicle.
AB  - A model, based on the principles of continuum mechanics, is presented for the
      analysis of cell-velocity fields within wool follicles. The model requires
      specification of three follicle characteristics in the form of spatially varying
      fields: viscosity, cell density and cell production rate. The viscosity is
      introduced as an attempt to model both complex intercellular interactions and
      individual cell deformation as the cells move. It is demonstrated that the
      distribution of cell production is more important than axial variation in
      viscosity in determining the overall flow pattern.

PMID- 9574971
TI  - Preventing throwing injuries.

PMID- 9574972
TI  - Systemic and topical antimicrobial therapy in periodontics.

PMID- 9574973
TI  - Aesthetics and plastic surgery in periodontics.

PMID- 9574974
TI  - Supportive periodontal treatment and retreatment in periodontics.

PMID- 9574975
TI  - Biological structure of the normal and diseased periodontium.

PMID- 9574976
TI  - The pathogenesis of periodontitis.

PMID- 9574977
TI  - Diagnostic techniques in periodontology.

PMID- 9574978
TI  - Mechanical and chemical supragingival plaque control.

PMID- 9574979
TI  - Surgical, nonsurgical, occlusal and furcation therapies.

PMID- 9574980
TI  - Official satellite symposium of the 2nd Congress of the European Association for
      Clinical Pharmacology and Therapeutics (EACPT): Clinical pharmacology of P
      glycoprotein and related transporters. Part II. Berlin, Germany, September 16,
      1997.

PMID- 9574981
TI  - [Occupational health of oil and gas industry workers in Russia].

PMID- 9574983
TI  - [Environmental impact on the formation of the public opinion among the urban
      population with developed oil refining industry, chemical petroleum industry and
      chemical industry].
AB  - The research proved oil-processing, petrochemical and chemical enterprises to be
      potent releasers of chemical hazards containing in industrial waste. The
      petrochemical and oil enterprises pollute environment and deteriorate sanitary
      conditions in populated area. The residents evaluate actual ecologic danger
      adequately. Sociologic analysis of how city dwellers assess quality of their
      environment and health is quate objective indicator of urban ecology and could be
      assigned to priority methods of ecologic and hygienic studies.

PMID- 9574982
TI  - [Characteristics of affect in chronic intoxication by non-symmetrical
      dimethylhydrazine, hydrocarbons and nitroglycols].
AB  - The authors analyze emotional features in workers with occupational exposure to
      hydrazines, hydrocarbons and nitroglycols. Chronic occupational poisoning with
      those chemicals induce numerous emotional symptoms that are specific and varying
      in severity. The materials presented by authors could be interesting for
      occupational therapist, internist and psychiatrist for early diagnosis of chronic
      occupational intoxications, treatment of emotional disorders in workers and
      better occupational safety.

PMID- 9574984
TI  - [The impact of industrial factors of oil processing plant on serum lipoproteins].
AB  - The study covered serum lipoproteins in workers engaged into production of higher
      fatty alcohols at oil-processing plant. The industrial factors appeared to induce
      changes in serum lipoproteins composition: lower share of High Density
      Lipoproteins and higher share of Very Low Density Lipoproteins. On the background
      of cardiovascular and gastrointestinal diseases, the occupational hazards may
      precipitate and aggravate alterations of serum lipoproteins composition in the
      workers.

PMID- 9574985
TI  - [Morbidity with temporary disability in workers at nickel industry with carbonyl
      based methods].
AB  - Morbidity levels in carbonyl method of nickel production are proved to depend
      mostly on occupational conditions rather than on age and length of service. The
      highest morbidity with transitory disablement is seen in the main occupational
      group, so sanitary, technical, therapeutic and prophylactic measures are required
      to eliminate causes of the high morbidity.

PMID- 9574986
TI  - [Chronic intoxication by fluor manifesting as pathological changes in connective
      tissues resulting in premature aging (analytical review)].

PMID- 9574987
TI  - [The use of pupillometry for the timely diagnosis of the intoxication by
      cholinesterase inhibitors].
AB  - The article deals with diagnostic potential of new generation pupillometers
      having hi-tech units and using up-to-date methods of information processing.
      Those pupillometers proved to be effective for express diagnosis of
      intoxications.

PMID- 9574988
TI  - [The use of color sensometry for the detection of early signs of exposure to
      nitric ethers].
AB  - The article deals with changes in color sensation under exposure to nitroesther
      vapors. Lower sensitivity to blue color is an early sign of exposure to the
      chemical hazards.

PMID- 9574989
TI  - [On the regeneration of transforming reagents in the spray method for the
      determination of ammonium concentration].
AB  - Aerosol method detecting low concentrations of ammonium involves passage of the
      analysed gas over crystal hydrate of iron nitrate with consequent registration of
      the aerosol obtained. The method is sensitive and precise due to direct
      correlation between concentration of the dispersed substance and ammonium level.
      For precise evaluation and its effectiveness, the crystal hydrate of iron nitrate
      should be kept over 55-65% nitric acid solution before the analysis.

PMID- 9574990
TI  - [Experimental data for the substantiation of allowable levels of several new
      herbicides (basta, furore-super) in the air of working area].

PMID- 9574991
TI  - [The time of the effect as the criterion for the degree of the effect].

PMID- 9574992
TI  - [Epidemiological aspects of joint diseases in coal miners].

PMID- 9574993
TI  - [Psychophysiological signs in workers exposed to chemicals].

PMID- 9574994
TI  - [Chronic methanol poisoning].

PMID- 9574995
TI  - [Disease characteristics of the population on the territory of the city of Kirovo
      Chepetsk].
AB  - Medical and ecologic evaluation of ecologic situation in Kirovo-Tchepetsk (Kirov
      region) included study of morbidity in the town and referent territories. Levels
      and dynamics of morbidity, prevalence, number of pathologic processes in children
      and other parameters could characterize the town as an ecologically unfavorable
      territory.

PMID- 9574996
TI  - Cultural literacy: is it important?

PMID- 9574997
TI  - Clinical research as community outreach.

PMID- 9574998
TI  - Treatment of attention-deficit hyperactivity disorder by different physician
      specialties.

PMID- 9574999
TI  - A "classic" case of borderline personality disorder.

PMID- 9575000
TI  - Antipsychotic medications and fertility.

PMID- 9575001
TI  - Medical necessity: its impact in managed mental health care.

PMID- 9575002
TI  - Predictors of being expelled from and dropping out of alcohol treatment.

PMID- 9575003
TI  - Implementing a statewide outcomes management system for consumers of public
      mental health services.
AB  - The authors describe the development and implementation of an outcomes management
      system designed to measure outcomes and processes of care for public mental
      health consumers in Arkansas. The public-academic project was implemented in 1995
      and is based on the Shewhart-Deming model of continuous quality improvement. All
      15 community mental health centers (CMHCs) in the state participate in the
      project, which prospectively measures longitudinal outcomes of care for the
      tracer conditions of major depression and schizophrenia. Multiperspective
      measurement tools are used to measure patients' psychiatric status and general
      health status at periodic intervals; information is gathered on functioning,
      symptoms, severity of illness, social factors, demographic characteristics, and
      quality of life. A problem encountered during implementation was the relatively
      low rate of referral of patients with the tracer conditions for monitoring.
      Voluntary rather than mandatory participation in the outcomes management system
      by the CMHCs as well as clinicians' misperceptions about the system's purpose and
      concerns about confidentiality may have partly accounted for the low rate.

PMID- 9575004
TI  - Compliance with medication regimens for mental and physical disorders.
AB  - OBJECTIVE: The authors reviewed research on medication compliance in psychiatric
      treatment and compared compliance rates with compliance rates in treatment of
      physical disorders. METHODS: MEDLINE was used to locate reports in the literature
      on medication compliance in psychiatric treatment for the years 1975 through
      1996. These reports and studies cited in the reports were reviewed to determine
      the methods used to assess compliance and the compliance rates reported. Ten
      reports describing assessment methods and including medication compliance rates
      for antidepressant medication and 24 reports for antipsychotic medication were
      selected. They were compared with 12 reports that used microelectronic monitoring
      to assess medication compliance of patients with a range of nonpsychiatric
      disorders. RESULTS: Studies of psychiatric patients used various methods of
      estimating medication compliance, including interviews with patients, clinicians'
      judgment, and pill counts, but overall showed low rates of compliance. Patients
      receiving antipsychotics took an average of 58 percent of the recommended amount
      of the medications, with a range from 24 to 90 percent. Patients receiving
      antidepressants took 65 percent of the recommended amount, with a range from 40
      to 90 percent. The mean compliance rate for patients with physical disorders was
      76 percent, with a range from 60 to 92 percent, although the microelectronic
      monitoring showed frequent omission of doses and discontinuation of medication.
      CONCLUSIONS: Compliance with medication regimens among patients with psychiatric
      disorders may be lower than among patients with physical disorders. However, the
      difference may be largely attributable to the methods used for estimating
      compliance. The findings suggest the need for new and improved methods for
      monitoring compliance and increasing patients' compliance with pharmacotherapy.

PMID- 9575005
TI  - Changes in questions about psychiatric illness asked on medical licensure
      applications between 1993 and 1996.
AB  - OBJECTIVE: This study examined the nature of questions about previous mental
      illness, physical illness, and substance abuse asked on applications for state
      medical licensure, partly to determine if questions focused more appropriately on
      any current, rather than past, disability. METHODS: In 1993 and 1996 the 66
      members of the Federation of State Medical Boards of the United States, Inc.,
      were asked to provide copies of the forms they used for medical licensure
      applications and renewal. The forms were reviewed to determine the presence of
      questions about previous mental illness, physical illness, and substance abuse
      and whether the questions specifically addressed the effects of the condition on
      the ability to practice medicine. RESULTS: On initial licensure applications,
      medical boards commonly asked questions about mental illness. Seventy-five
      percent of responding boards did so in 1993, and 80 percent did so in 1996. The
      proportion of boards that inquired about whether the mental illness might affect
      the applicant's ability to practice medicine increased from 42 percent in 1993 to
      75 percent in 1996. Applicants were asked about substance abuse by 83 percent of
      the boards in 1993 and by 94 percent in 1996. Boards asked about physical
      conditions less often than mental conditions but were more likely to ask about
      physical conditions in 1996 (65 percent) than in 1993 (49 percent). Questions
      about physical illness almost always addressed the effect of the condition on
      medical practice. On license renewal requests, medical boards were less likely to
      ask questions about mental conditions, substance abuse, and physical illnesses
      than on the original applications. Among boards that asked about mental illness
      on renewal forms, the proportion of boards that asked about the effect of mental
      conditions on ability to practice medicine increased from 60 percent in 1993 to
      90 percent in 1996. CONCLUSIONS: Medical boards commonly ask questions about
      mental illness on licensure application and renewal forms. In many states, such
      questions changed between 1993 and 1996 to emphasize impairment resulting from
      mental illness and to use similar wording for mental disorders and physical
      conditions.

PMID- 9575006
TI  - Effect of staff debriefing on posttraumatic stress symptoms after assaults by
      community housing residents.
AB  - OBJECTIVE: The study examined the efficacy of critical incident stress debriefing
      in ameliorating the impact of posttraumatic stress on direct care psychiatric
      workers after a traumatic event at work. METHODS: Sixty-three direct care workers
      from two areas in Sydney, Australia, who worked in community residences for
      persons with developmental and psychiatric disabilities were surveyed about
      symptoms of intrusive thoughts, avoidance, and hyperarousal one week after they
      experienced an assault or another type of work-related trauma. Survey respondents
      included 14 workers who requested and attended a one-session critical incident
      stress debriefing during the week after the incident, 18 workers from the same
      area of Sydney who had access to the intervention but chose not to attend, and 31
      who worked in an area where the intervention was not available. RESULTS: Sixty
      two workers reported symptoms of posttraumatic stress. Lower levels were reported
      by workers in the area where the intervention was available. When other factors
      were controlled, the lowest levels of stress were reported by workers to whom the
      debriefing was available but who chose not to attend. No significant difference
      in overall stress reduction in the week after the incident was found between the
      workers who received the intervention and those who did not. CONCLUSIONS:
      Although critical incident stress debriefing was evaluated positively by the
      majority of participants, aspects of the intervention such as its timing and the
      work environment in which it is offered may affect the degree to which
      participants benefit from it.

PMID- 9575008
TI  - Delusions and symptom-consistent violence.
AB  - OBJECTIVE: The study examined the extent to which delusions motivate violent
      behavior among psychiatric patients with a history of delusions. METHODS: Fifty
      four psychiatric inpatients identified by hospital staff as having delusions were
      interviewed about their history of delusions and incidents of violence that were
      concurrent with delusions. Raters used a 5-point scale to estimate the degree to
      which each reported incident of violence was motivated by a concurrent delusion.
      A second set of raters used a 5-point scale to estimate the severity of the
      violent incidents. RESULTS: Raters' mean estimate indicated overall that violent
      incidents were probably not motivated by concurrent delusions. However, a
      significant minority of violent subjects (40 percent) reported at least one
      violent incident that was judged to be probably or definitely motivated by a
      concurrent delusion. A smaller subgroup of violent subjects (17.5 percent)
      reported at least one incident that was judged to be both extremely violent and
      definitely motivated by a concurrent delusion. CONCLUSIONS: Delusional motivation
      of violence is rare, but a moderate risk exists that delusions will motivate
      violence at some time during the course of a violent patient's illness.

PMID- 9575007
TI  - Women's safety in recovery: group therapy for patients with a history of
      childhood sexual abuse.
AB  - The literature on group therapies for women with histories of childhood sexual
      abuse has focused on outpatient treatments. A model of group treatment for
      inpatients and partial hospital patients is described here. "Women's Safety in
      Recovery" is a first-stage trauma recovery group that promotes mastery of current
      life stressors and prevents regression through the use of psychoeducation about
      abuse effects, the practice of problem-solving skills, and supportive, topic
      focused discussion. The group is structured in three one-week modules that
      patients can begin or leave at any time.

PMID- 9575009
TI  - Low cholesterol and violence.
AB  - OBJECTIVE: The association between violent behavior and low serum total
      cholesterol levels was examined in a psychiatric inpatient population with
      diverse diagnoses. METHODS: The study used a case-control design to compare the
      cholesterol levels of patients in a long-term psychiatric hospital who had a
      history of seclusion or restraints (N = 20) and those who did not (N = 20). A low
      cholesterol level was defined as less than 180 mg/dL. RESULTS: A strong
      association was found between low cholesterol levels and violent behavior (odds
      ratio = 15.49), an association that was not due to age, race, sex, or diagnosis.
      The finding was consistent whether mean levels or dichotomized levels of
      cholesterol were examined. Physical health, cholesterol-lowering medication,
      current alcohol use, or unusual diets could not explain the results. However, the
      raw frequency of episodes of seclusion or restraint as an indicator of the
      frequency of violent behavior was not associated with cholesterol level.
      Dichotomizing cholesterol levels at 180 mg/dL yielded high sensitivity (90
      percent) for predicting violent behavior but at the cost of low specificity (65
      percent). CONCLUSIONS: The results support the hypothesis that an association
      exists between low cholesterol and violent behavior among psychiatric patients
      but argue against using cholesterol level as a screening tool for predicting
      violent behavior.

PMID- 9575010
TI  - The child advocacy team in legal actions.
AB  - This paper provides a general description of child advocacy teams, which are
      formed in difficult child custody or abuse and neglect cases. They are created
      when a judge asks that a team assist in determining the child's psychological
      status and developmental needs, assessing parenting capacities, developing a
      treatment plan, and monitoring the family's progress. The team consists of
      representatives from the legal, social service, mental health, and educational
      systems. The author describes the principles and techniques of child advocacy,
      characteristics of the professional systems involved, and phases of the team's
      operation, such as the planning conference, the therapeutic-evaluation process,
      team meetings, report preparation, and courtroom participation. Outcomes of 77
      cases handled by a University of Wisconsin child advocacy team over the past 20
      years are presented to show that a team is an effective means of integrating
      professional and volunteer activities for a family during a child protection or
      divorce action.

PMID- 9575011
TI  - Mental illness and nursing home reform: OBRA-87 ten years later. Omnibus Budget
      Reconciliation Act.
AB  - OBJECTIVE: This literature review examined data on the effects of nursing home
      reform initiated by the Omnibus Budget Reconciliation Act of 1987 (OBRA), with
      particular attention to use of antipsychotic medications, use of physical
      restraints, and preadmission screening. METHODS: Data on the outcomes of the
      nursing home reform were obtained from a MEDLINE search of peer-reviewed articles
      from January 1985 through January 1997 and from PsycINFO from 1967 through 1997.
      RESULTS AND CONCLUSIONS: Survey and observational data suggest that the reform
      legislation is having the intended impact, especially in reducing the use of
      antipsychotic medications and physical restraints in nursing homes. Preadmission
      screening of nursing home residents with mental illness is the most widely
      criticized component of the reform, and the component that has been the subject
      of the fewest data-based studies. More data are needed to describe the economic
      costs of the reform and to link the reform to improvements in nursing home
      residents' quality of life.

PMID- 9575012
TI  - CT scans of first-break psychotic patients in good general health.
AB  - A computed tomography (CT) scan of the head is often routine for patients with
      new-onset psychosis to rule out somatic causes. Charts of 127 such patients
      admitted to a major military medical center were examined. Most patients were
      young and otherwise in good health. Relationships were examined between CT scan
      findings and demographic variables, seizure history, neurological abnormalities,
      and discharge diagnosis. None of the 127 patients had an abnormal scan; four had
      incidental findings. Incidental findings were strongly associated with ethnic
      minority status but not with neurologic abnormalities, seizure history, or
      diagnosis. Findings suggest that routine CT scans for all newly psychotic
      military patients may not be warranted.

PMID- 9575013
TI  - Interagency collaboration in services for people with co-occurring mental illness
      and substance use disorder.
AB  - Historically the divisions between the mental health and substance abuse fields
      have been so deep that attempts to provide coordinated treatment across service
      sectors for people with dual diagnoses of psychiatric disorder and substance use
      disorder have failed. The authors describe a program in Maine designed to develop
      collaboratives, or communities of providers, who work together to offer
      coordinated mental health and substance abuse treatment and support. Surveys of
      provider agencies in one collaborative conducted one year and two years after the
      collaborative was established showed an increase in interagency referrals, joint
      assessments of clients, and jointly sponsored training and client services.

PMID- 9575014
TI  - Ethnic differences in response to fluoxetine in a controlled trial with depressed
      HIV-positive patients.
AB  - This study examined ethnic differences in response to antidepressant treatment.
      One hundred eighteen depressed HIV-positive patients entered an eight-week
      controlled trial of fluoxetine. Nineteen percent were black and 14 percent were
      Latino; the remaining two-thirds were white. Attrition was greater among Latinos
      than either blacks or whites. Black patients were more likely than whites to be
      nonresponders to fluoxetine. Latinos were more likely to respond to placebo
      compared with blacks and whites. Ethnic groups did not differ in the presence of
      treatment-emergent side effects.

PMID- 9575015
TI  - Replicated declines in assault rates after implementation of the Assaulted Staff
      Action Program.
AB  - A program to address the psychological sequelae of patients' assaults on
      psychiatric health care staff--the Assaulted Staff Action Program (ASAP)--was
      previously shown to be associated with a notable decline in the assault rate at
      the state hospital where it was implemented. This study examined whether these
      findings would be replicated when ASAP was introduced at three additional state
      hospitals. Assault rates during the three months before implementation were
      compared with rates in the first four quarters after implementation. Each
      facility reported a similar significant decline in rates during the first quarter
      after implementation and no additional declines in the next three quarters.

PMID- 9575017
TI  - Family caregivers and confidentiality.

PMID- 9575018
TI  - Risperidone in PTSD.

PMID- 9575016
TI  - Informed consent in schizophrenia research.

PMID- 9575019
TI  - Residential treatment for patients in crisis.

PMID- 9575020
TI  - Employers must comply with Parity Act before seeking exemption, Clinton
      Admininstration rules.

PMID- 9575021
TI  - Rural mental health work group calls for better training, more flexibility in
      provision of services.

PMID- 9575022
TI  - New guide helps primary care clinicians identify and treat patients with
      substance abuse problems.

PMID- 9575023
TI  - [Activities of the Kharbinsk plague control station in 1903-1925].

PMID- 9575024
TI  - Hand in Hand with Rett Syndrome. Proceedings of the World Congress on Rett
      Syndrome. Gothenburg, Sweden, August 30-September 1, 1996.

PMID- 9575025
TI  - Helping health professionals deal with violence.
AB  - Violence towards health professionals is defined as any incident in which a
      health professional experiences abuse, threat, fear or the application of force
      arising out of the course of his or her work, whether or not they are on duty. It
      emerges that no single theory can adequately explain the phenomenon, and
      perceptions about incidence and prevalence are distorted by the media. There is
      consistent and variable reporting but a high incidence and prevalence undoubtedly
      exists within health care. Health professionals and less experienced nurses in
      particular have been found to be most at risk. A strategic approach is needed to
      the development and implementation of workplace-specific solutions. Health
      professionals have a right to expect that violence at work is minimized but it
      would be unrealistic to expect it to be eradicated.

PMID- 9575026
TI  - Phenotypic identification of Aeromonas genomospecies from clinical and
      environmental sources.
AB  - A collection of 983 Aeromonas isolates from environmental and clinical sources
      have been identified to the genomospecies level. A phenotypic method identified
      93% of the strains. The use of citrate and the production of acid from sorbitol
      enabled the members of the Aeromonas hydrophila complex to be separated. The most
      common genomospecies from intestinal sources were Aeromonas veronii biotype
      sobria and Aeromonas caviae. The former, together with A. hydrophila, was the
      most frequently isolated species of extraintestinal origin. Most pathogenic
      species were very prevalent in environmental samples, with A. veronii biotype
      sobria being the most common in lakes and reservoirs (41.5%) and in treated
      drinking water (25.0%), and A. caviae was the most common in sea water (26.0%)
      and milk products (35.5%). Aeromonas hydrophila (18.1%) was the second most
      prevalent species isolated in untreated drinking water. Since Aeromonas
      infections are generally regarded as a water- and food-borne diseases, the high
      environmental prevalence of these pathogenic genomospecies should be regarded as
      an important threat to public health.

PMID- 9575027
TI  - Chemically emulsified crude oil as substrate for bacterial oxidation: differences
      in species response.
AB  - Four bacterial species were tested for their abilities to oxidize alkanes in
      crude oil in water emulsions. The emulsions were prepared by nonionic sorbitan
      ester and polyoxyethylene ether surfactants. The oxidation rates were measured as
      initial attack on the emulsions by resting cells pregrown in crude oil media. The
      bacteria responded differently and both positive and negative effects of
      surfactant amendment were observed. The same surfactant affected various bacteria
      differently and the response to the surfactant amendment depended on the
      physiological state of the bacteria, i.e., exponential versus stationary growth
      phase. The surfactants caused a marked decrease in cell adhesion to the oil phase
      for all the bacteria, irrespective of the growth phase and any positive effect on
      the oil oxidation rates. The response of Deleya salina 128 to polyoxyethylene
      surfactant emulsified crude oil depended on the length and structure of the
      hydrophobic tail, the number of hydrophilic ethoxy groups, and the relative
      proportion of the hydrophobic and hydrophilic constituents in the individual
      surfactant.

PMID- 9575028
TI  - [The Grade-of Membership analysis: an approach to the psychiatric
      classification].

PMID- 9575029
TI  - [The patient and family satisfaction with the department of mental health in
      Rome].
AB  - OBJECTIVE: Satisfaction's measurement with Mental Health Services in patients and
      their relatives. DESIGN: Satisfaction scale administration to the patients who
      were treated in community-based psychiatric service from 1.1.1996 to 31.3.1996
      and the relatives who were primarily involved in caring for the patient. SETTING:
      The ASL Rome "C" community-based psychiatric service. MAIN OUTCOME MEASURES:
      Verona Service Satisfaction Scale-54, a multidimensional instrument which measure
      satisfaction with community-based psychiatric service. RESULTS: Main results (301
      scales for patients, 163 scales for relatives), pointed out for patients a higher
      satisfaction for the technical and interpersonal skills of psychiatrists and
      psychologists (score of specific items > 4). Lowest scores of satisfaction were
      towards the appearance, comfort level and physical layout of the facility (score
      2.95) and towards the response of the service to emergencies during the night,
      weekend and Bank Holidays (score 2.87). Relatives were not particularly keen for
      the item regarding help to find open employment (score 2.76). Furthermore
      patients and their relatives gave a negative evaluation of the publicity and
      information offered by Mental Health Services. Dimension's analysis reaches the
      same conclusions deduced items's average score. The result of this study
      emphasizes the patients higher degree of satisfaction than the relatives.
      CONCLUSIONS: The above results point out three aspects to be improved by the
      Mental Health Service in order to satisfy the demands of the patients and
      relatives: 1. appearance, comfort level and physical layout of the facility, 2.
      publicity and information, 3. social activities and social skills.

PMID- 9575030
TI  - [Psychotherapies in psychosocial centers in Lombardia: a point of view of
      psychiatrists and psychologists].
AB  - OBJECTIVE: The purpose of this study is the systematic analysis of operators'
      points of view about psychotherapies concretely performed in the Public
      Psychiatric Public Services and inside the global operating mode of the
      assistance. SETTING: The study has involved 26 CPS selected randomly in
      Lombardia. The sample has been built with 73 psychiatrists and 42 psychologists.
      MAIN OUTCOME MEASURES: All the therapeutists involved in this research have been
      submitted to a question-form querying socio-anagraphic data, professional
      training, orientations, operating modes in their CPS, rules and objectives of
      their psycotherapies, observations and evaluations about psychoterapic treatments
      and their effects. RESULTS AND CONCLUSIONS: Psychiatrists and psycologists
      working in CPS, mostly the younger ones (less than 45 years old), followed a
      personal training in over the 70% of the cases. The prevalent orientation is the
      psycoanalityc one in both the categories. The most part of therapeutists deems
      that there has been an evolution in their way of conceiving psychiatry inside the
      public service. The lines at these evolutions have been mentioned explicitly in
      the article. Psychiatrists and psycologists, even with some concrete differences;
      seems to have mostly homogeneous points of view: psychiatrists have a more
      flexible vision of which practices can be considered as a psychotherapy, whereas
      psycologists are more rigorously linked to theoric reference models and to rules
      learnt during their training. They are both slightly favourable to the use of
      psychotherapies in their services, even if, as a matter of fact, they are used by
      just a few patients. No contrast between psycotherapy and psycopharmacology has
      been detected from operators' answers. These practices seem to be both considered
      useful and integrable.

PMID- 9575031
TI  - [Life skills profile (LSP). Presentation].

PMID- 9575032
TI  - [A training course of SCAN use (Schedules for Clinical Assessment in
      neuropsychiatry)].

PMID- 9575033
TI  - Literature watch.

PMID- 9575034
TI  - Reflux esophagitis in duodenal ulcer patients.

PMID- 9575035
TI  - Experimental Biology 1997. Symposium on pathophysiology of cardiorenal systems in
      obesity. A symposium in memory of A. Clifford Barger.

PMID- 9575036
TI  - VIII Annual meeting of the GSIPC (Gruppo di Studio Italiano di Patologia
      Cardiovasculare). Pavia, Italy, November 21-22, 1997. Abstracts.

PMID- 9575037
TI  - Training-induced alterations in glucose metabolism during exercise.

PMID- 9575038
TI  - Premature polypsychopharmacology.

PMID- 9575039
TI  - Ultrastructural localization of glycolytic enzymes on sarcoplasmic reticulum
      vesticles.
AB  - We have previously obtained indirect evidence that sarcoplasmic reticulum (SR)
      vesicles from cardiac and skeletal muscle contain the complete chain of
      glycolytic enzymes from aldolase to pyruvate kinase. To investigate directly
      whether pyruvate kinase and other glycolytic enzymes are anatomically associated
      with the SR, electron microscopic immunogold++ labeling studies were carried out
      in isolated SR vesicles using specific primary antibodies against selected
      glycolytic enzymes and Ca2+-ATPase, and appropriate secondary antibodies labeled
      with 6-nm or 12-nm gold particles. Pyruvate kinase was broadly dispersed on the
      cytoplasmic side of the SR membrane of both cardiac and skeletal muscle vesicles.
      With 6-nm gold particles, density of binding to pyruvate kinase was 2522 +/- 445
      and 4171 +/- 1379 particles/microm2 for cardiac and skeletal muscle SR,
      respectively. Binding densities to Ca2 +/- ATPase were similar (2550 +/- 639
      particles/ microm2 for cardiac SR, 3877 +/- 408 particles/microm2 for skeletal
      muscle SR). Immunogold labeling of ultrathin sections indicated that pyruvate
      kinase was attached to the SR membrane and located immediately adjacent to the
      Ca2+-ATPase. Aldolase and glyceraldehyde phosphate dehydrogenase were also found
      to be attached to the cytoplasmic side of SR vesicles and located in close
      proximity to Ca2+-ATPase. These results provide the first ultrastructural
      evidence that glycolytic enzymes are anatomically associated with SR membranes
      and located near the SR C2+-ATPase. The results further support the hypothesis
      that ATP generated by SR-associated glycolytic enzymes is coupled to SR Ca2+
      active transport.

PMID- 9575040
TI  - Tyramide amplification allows anterograde tracing by horseradish peroxidase
      conjugated lectins in conjunction with simultaneous immunohistochemistry.
AB  - Current protocols for a combined approach of anterograde tracing with
      carbocyanine dyes or horseradish peroxidase (HRP) conjugates and
      immunohistochemistry represent a compromise between sensitive detection of the
      tracer and the immunohistochemical procedure. Therefore, it was investigated
      whether the use of tyramide amplification allows sensitive anterograde tracing
      with wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in
      conjunction with simultaneous immunohistochemistry. Vagal afferents were
      anterogradely labeled by injection of WGA-HRP into the nodose ganglion of rats.
      By use of tyramide-biotin amplification, a dense fiber plexus of vagal afferents
      was visualized centrally in the nucleus of the solitary tract and in retrogradely
      labeled neurons in the dorsal vagal nucleus. In the esophagus and duodenum, large
      and small-caliber vagal fibers and terminals could be demonstrated comparably to
      conventional tracing technique using carbocyanine dyes or WGA-HRP and TMB
      histochemistry. Combination with immunohistochemistry could easily be done,
      requiring only one more incubation step, and did not result in loss of
      sensitivity of the tracing. With this method and confocal microscopy, the
      presence of Ca binding proteins in vagal afferent terminals could be
      demonstrated. Tyramide amplification allows sensitive anterograde tracing with
      low background staining in conjunction with immunohistochemistry of a-axonal
      markers.

PMID- 9575041
TI  - A new method for intense staining of myelin.
AB  - We describe a new method for intense staining of myelin. The stain involves
      immersing frozen or vibratome sections of 4% normal horse serum. A DAB reaction
      is then carried out, which results in the deposition of reaction product in
      myelin sheaths. On intensification of this reaction product using the silver
      enhancement technique described by Gorcs, myelin stains an intense black color,
      making the preparations suitable for photography. The stain is especially useful
      for determining the distribution of myelinated fibers in gray matter.

PMID- 9575042
TI  - Immunocytochemical localization of Fos in perfused nonhuman primate brain tissue:
      fixation and antisera selection.
AB  - Immunocytochemical localization of immediate early gene proteins, such as Fos,
      provides a powerful tool with which to demonstrate activated neuronal populations
      in response to specific stimuli. In contrast to studies using rat brain tissue
      that consistently show good Fos detection with a variety of antisera, studies
      using brain tissue from other species yield variable Fos detection. This may be
      partly due to differences in Fos protein sequences among species or to perfusion
      and fixation methods. To determine the ability of various Fos antisera to detect
      neuronal activation in nonhuman primate tissue, we tested nine Fos antisera and
      compared these antibodies under conditions of intense or physiological
      stimulation. Monkey brain tissue was either perfused and postfixed with 4%
      paraformaldehyde or perfused with 4% paraformaldehyde and postfixed with 2.5%
      acrolein in 4% paraformaldehyde. In rat tissue, stained for comparison, several
      antisera resulted in good to excellent Fos detection. However, few antisera
      tested in monkey tissue resulted in excellent Fos staining. We demonstrate that
      detection of Fos in monkey brain tissue perfused with 4% paraformaldehyde can be
      improved by postfixation in a dilute acrolein solution. Our findings emphasize
      the importance of choosing appropriate antisera and perfusion-fixation procedures
      to optimize Fos detection in nonhuman primate tissue.

PMID- 9575043
TI  - Conversion of aminonitrotoluenes by fungal manganese peroxidase.
AB  - Preparations of extracellular manganese peroxidase from the white-rot fungus
      Nematoloma frowardii and the litter decaying fungus Stropharia rugosoannulata
      converted rapidly the main intermediates of the explosive 2,4,-trinitrotoluene-
      the aminonitrotoluenes. In a cell-free system, 2-amino-4,6-dinitrotoluene, 4
      amino-2,6-dinitrotoluene and 2,6-diamino-4-nitrotoluene were degraded without
      formation of identifiable metabolites. Radioactive experiments using a complex
      mixture of uniform ring-labeled 14C-TNT reduction products demonstrated the
      partial direct mineralization of these compounds by manganese peroxidase. The
      extent of aminonitrotoluene conversion as well as the release of 14CO2 from TNT
      reduction products were considerably enhanced in the presence of thiols like
      reduced glutathione or the amino acid L-cystein, which probably act as secondary
      mediators.

PMID- 9575045
TI  - Illiteracy as an adverse side effect of the computer age.

PMID- 9575046
TI  - Release of endogenous glutamate and gamma-aminobutyric acid from rat striatal
      tissue slices measured by an improved method of high performance liquid
      chromatography with electrochemical detection.
AB  - The release of endogenous glutamate and gamma-aminobutyric acid (GABA) from rat
      brain tissue slices was studied using a tissue slice assay in which detectable
      amounts of the amino acids were released from 1-2 mg of tissue. An improved
      method of high performance liquid chromatography (HPLC) with electrochemical
      detection was employed to measure both glutamate and GABA after derivatization
      with o-phthalaldehyde and sulphite in a single isocratic HPLC analysis. The non
      endogenous amino acid, homoglutamine, was used as an internal standard in
      verifying the consistent derivatization of amino acids and in quantifying amounts
      of glutamate and GABA released from the caudate-putamen tissue. The derivatized
      amino acids (1-30 pmol) were detected as chromatographic peaks eluting at
      baseline level and free of significant interfering co-eluates in a 25-30 min
      analysis time.

PMID- 9575047
TI  - [Croatian terminology in AIDS].

PMID- 9575044
TI  - Design, synthesis, and antiviral activity of alpha-nucleosides: D- and L-isomers
      of lyxofuranosyl- and (5-deoxylyxofuranosyl)benzimidazoles.
AB  - Several 2-substituted alpha-D- and alpha-L-lyxofuranosyl and 5-deoxylyxofuranosyl
      derivatives of 5,6-dicholro-2-(isopropylamino)-1-(beta-L-ribofuranosyl)
      benzimidazole (1263W94) and 2,5,6-trichloro-1(beta-D-ribofuranosyl)benzimidazole
      (TCRB) were synthesized and evaluated for activity against two herpesviruses (HSV
      1 and HCMV) and for their cytotoxicity against HFF and KB cells. Condensation of
      1,2,3,5-tetra-O-acetyl-L-lyxofuranose (2a) with 2,5,6-trichlorobenzimidazole (1)
      yielded the alpha-nucleoside 3a. The 2-bromo derivative and 2-methylamino
      derivative were prepared by treatment of 3a with HBr followed by deprotection or
      from methylamine, respectively. Compound 3a was deprotected and the resultant
      nucleoside used to prepare the 2-cyclopropylamino and 2-isopropylamino
      derivatives. The 2-alkylthio nucleosides were prepared by condensing 2a with 5,6
      dichlorobenzimidazole-2-thione followed by deprotection. Alkylation of this
      adduct gave the 2-methylthio and 2-benzylthio derivatives. Condensation of 5
      deoxy-1,2,3-tri-O-acetyl-L-lyxofuranosyl, prepared from L-lyxose, with 1 or 2
      bromo-5,6-dichlorobenzimidazole (15), followed by deprotection, gave the 2-chloro
      or 2-bromo-5'-deoxylyxo-furanosyl derivative, respectively. The cyclopropylamino
      derivative was prepared from the 2-chloro derivative. All D-isomers were prepared
      in an analogous fashion from D-lyxose. Either compounds were inactive against HSV
      1 or weak activity was poorly separated from cytotoxicity. In contrast, the 2
      halogen derivatives in both the alpha-lyxose and 5-deoxy-alpha-lyxose series were
      active against the Towne strain of HCMV. The 5-deoxy alpha-L analogues were the
      most active, IC50's = 0.2-0.4 microM, plaque assay; IC90's = 0.2-2 microM, yield
      reduction assay. All of the 2-isopropylamino or 2-cyclopropylamino derivatives
      were less active (IC50's = 60-100 microM, plaque assay; IC90's = 17-100 microM,
      yield reduction assay) and were not cytotoxic. The methylamino, thio, and
      methylthio derivatives were neither active nor cytotoxic. The benzylthio
      derivatives were weakly active, but this activity was poorly separated from
      cytotoxicity. The alpha-lyxose L-isomers were more active in a plaque assay
      against the AD169 strain of HCMV compared to the Towne strain, thereby providing
      additional evidence of antiviral specificity.

PMID- 9575048
TI  - Amiodarone prophylaxis for atrial fibrillation after cardiac surgery.

PMID- 9575049
TI  - Amiodarone prophylaxis for atrial fibrillation after cardiac surgery.

PMID- 9575050
TI  - Amiodarone prophylaxis for atrial fibrillation after cardiac surgery.

PMID- 9575051
TI  - Alcohol consumption and mortality in U.S. adults.

PMID- 9575052
TI  - Alcohol consumption and mortality in U.S. adults.

PMID- 9575053
TI  - Interferon for hepatitis C virus-negative type II mixed cryoglobulinemia.

PMID- 9575054
TI  - Antiplatelet therapy and patency of saphenous-vein bypass grafts in the legs.

PMID- 9575055
TI  - Noninvasive ventilation.

PMID- 9575056
TI  - Noninvasive ventilation.

PMID- 9575057
TI  - The rule of double effect.

PMID- 9575058
TI  - The rule of double effect.

PMID- 9575059
TI  - The rule of double effect.

PMID- 9575060
TI  - The rule of double effect.

PMID- 9575061
TI  - Tick-borne infection caused by Rickettsia africae in the West Indies.

PMID- 9575062
TI  - Case of propylthiouracil-induced ANCA associated small vessel vasculitis.

PMID- 9575063
TI  - Prescribing costs.

PMID- 9575064
TI  - False hope.

PMID- 9575065
TI  - [Proceedings of the 1st Congress of the Military Otolaryngologists and the Xth
      Jubilee Conference of the Military Health Service Otolaryngologists. 10 June
      1995].

PMID- 9575067
TI  - [Hepatitis C, diagnosis and treatment. 16-17 January 1007. Cite des Sciences et
      de Industrie, La Villette-75019 Paris].

PMID- 9575066
TI  - [New trends in transplantation. Wednesday 4 June 1997. Hotel Meridien
      Montparnasse-75014 Paris. Symposium].

PMID- 9575068
TI  - More on the history of pediatrics.

PMID- 9575070
TI  - Symposium on Nutrition, Brain Function, and Eating Disorders. Tel Aviv, Israel, 3
      4 November 1997. Abstracts.

PMID- 9575069
TI  - Telepresence and the practice of medicine. Look for machines to assist you, not
      replace you.

PMID- 9575071
TI  - [Underestimated consequences].

PMID- 9575072
TI  - [Dental deontology].

PMID- 9575073
TI  - [The patient in the center. The 27th annual meeting of the Swiss Society for
      Periodontology (SGP) in Bern of the 11th to 13th September 1997].

PMID- 9575074
TI  - [The implant-anchored overdenture examined by specialists. The 8th Update
      Congress on Clinical Prosthodontics. Turin 24-26 October 1997].

PMID- 9575075
TI  - Owls and early learning.

PMID- 9575076
TI  - Owls and early learning.

PMID- 9575077
TI  - Kaposi's sarcoma and protection from HIV dementia.

PMID- 9575079
TI  - Bailout for drug research institute.

PMID- 9575078
TI  - Kansas City institute's big plans.

PMID- 9575080
TI  - Listening in on the brain.

PMID- 9575081
TI  - A water generator in the Orion Nebula.

PMID- 9575082
TI  - A possible new approach to combating Staph infections.

PMID- 9575083
TI  - Anthropologists probe genes, brains at annual meeting.

PMID- 9575084
TI  - Signaling path may lead to better heart-failure therapies.

PMID- 9575085
TI  - Proteases, processing, and thymic selection.

PMID- 9575086
TI  - The future of human longevity: a demographer's perspective.

PMID- 9575087
TI  - Synthetic protease switch.

PMID- 9575088
TI  - Beauty in simplicity.

PMID- 9575089
TI  - Origin of the eukaryotic nucleus.

PMID- 9575091
TI  - Neither inbred nor extinct.

PMID- 9575090
TI  - The brain's normal function.

PMID- 9575092
TI  - UC fights tobacco company subpoena.

PMID- 9575093
TI  - Research drought looms afer Neurolab mission.

PMID- 9575094
TI  - A blow to the 'grandmother theory'.

PMID- 9575095
TI  - Tracking insulin to the mind.

PMID- 9575097
TI  - Versatile gene uptake system found in cholera bacterium.

PMID- 9575096
TI  - Genes may link ancient Eurasians, Native Americans.

PMID- 9575098
TI  - The interdependence of science and law.

PMID- 9575099
TI  - Sieves in sequence.

PMID- 9575100
TI  - Archael means and extremes.

PMID- 9575101
TI  - [Aleksandr Fedorovich Bilibin (on the centenary of his birth)].

PMID- 9575102
TI  - [Ia. V. Villie as a surgeon].

PMID- 9575103
TI  - [Laryngo-tracheal stenoses].

PMID- 9575104
TI  - 50 years of meetings. The Southwestern Surgical Congress.

PMID- 9575105
TI  - [Pseudotumors of salivary glands. Laryngeal oncocytosis. A case report].
AB  - We show briefly an update information covering a group of conditions affecting
      the salivary glands. The group is difficult to classify and even have originate
      controversial diagnoses. The group is denominated as pseudotumors of the salivary
      glands. Next in the article is reported the discovery of one case of laryngeal
      oncocytosis.

PMID- 9575106
TI  - [Malignant melanoma of the pinna].

PMID- 9575107
TI  - [Histochemical study with lectins in nasal polyposis].
AB  - Histochemical study done with lectins is useful in order to differentiate between
      several carbohydrates from glycoproteins and glycolipides present in cellular
      membranes. Plasma cells and eosinophils are very frequent findings in nose mucous
      of patients with nasal polyposis. Histochemistry with lectins of plasma cells
      show a reactivity of the cellular cytoplasma to ConA while the external cellular
      membrane stains with PNA.

PMID- 9575108
TI  - [The anamnesis in old people with equilibrium disorder].
AB  - Equilibratory troubles in aged individuals are the consequence of changes in
      vestibular, visual, proprioceptive, neuro-muscular and skeletal systems. Often
      related as well, to iatrogenic effects induced by pharmacological treatments. Its
      assessment is not easy at all because elderly population undergo physiological
      inability and so offer great difficulties in both diagnosis and management. At
      least informative data related to the equilibration must be collected: feelings,
      positional and postural unleashing factors, evolutive pattern, intercrises
      symptoms, cochlear and neurologic findings. Pharmacological treatments,
      associated pathologies and psycho-affective conditions as well. In the anamnestic
      model proposed by the AA. other helpful data in order to arouse clinical
      suspicion on vasculocerebral and vertebrobasilaris pathologies are contemplated.
      A sample concerning 51 patients more than 70-year-old with the gained descriptive
      results in detailed.

PMID- 9575109
TI  - [Cholesteatoma of the cerebellopontine angle. A case report].
AB  - In the paper is reported the case of a patient carrying a cholesteatoma located
      at the cerebellopontine angle. Firstly he came by us because of his auditive
      impairment and equilibratory troubles, as well. These are the reasons of this
      text: to review all aspects clinical, diagnostic and therapeutical of the
      disease.

PMID- 9575110
TI  - [Complete regression of a Warthin's tumor following the aspiration cytopuncture].
AB  - This paper reports a rare case of a 69-year-old man bearing a right parotid lump,
      measuring near 5 cm diameter, which diagnosis resulted a Warthin's tumor. The
      used procedure to reach the diagnosis was aspiration through a fine needle. Two
      months after the laboratory diagnosis--so within the preoperative term--we can
      corroborate the clinical and radiological missing of the growth. Review and
      analysis of etiologic and pathogenic mechanisms.

PMID- 9575111
TI  - [Auditory changes in spontaneous intracranial hypotension].
AB  - Descriptive report dealing with the auditive disturbances of 3 patients with
      spontaneous intracranial hypotension, disorder typified for orthostatic cephalea
      without a know ground explaining the descent of the cerebrospinal fluid pressure.
      The patients presented with hypoacusis, hyperacusis, feeling of plenitude,
      blockade and ear pressure. The clinical picture is supposed to be linked to a low
      endolabyrinthine pressure, secondary to an intracranial hypotension. Review of
      auditive symptoms reported in the bibliography among individuals showing benign
      intracranial hypertension and intracranial hypotension owing to several causes.

PMID- 9575112
TI  - [Kikuchi and Fujimoto disease ].
AB  - Kikuchi-Fujimoto disease (KF) is a new and uncommon malady of unknown etiology,
      first described in Japan. Clinically runs with neck adenopathies no larger than 2
      cm diameter. Young women are more frequently affected. Main features are fever
      and nocturnal swelling in half of cases. Laboratory findings are not
      diagnostically helpful and positive diagnosis is only reliable upon ganglion's
      histology. Be unaware of this sickness can arise confusion with a malignant
      lymphoma. The illness is harmless and autolimited in a few months term. We report
      a new case of KF disease, diagnosed through excision biopsy, after a previous
      needle biopsy had awakened one's suspicion about a non Hodgkin lymphoma.

PMID- 9575113
TI  - [Frontal ethmoidal mucocele. Clinical and therapeutic considerations].
AB  - In this paper are recalled the most important features of this sinusal condition,
      its behaviour, complications and so on. Regarding the management the A. recall to
      the classic surgery, well done, orderly and systematically planed, which give him
      always good outcomes. By the way accordingly to the promising it could be, he
      refers to endoscopic functional sinusal approach.

PMID- 9575114
TI  - [The treatment of congenital errors of metabolism].

PMID- 9575115
TI  - [Idiopathic hypercalciuria. How does one find exit from the labyrinth?].

PMID- 9575116
TI  - [Parvovirus B19 as infectious agent in infants].
AB  - OBJECTIVE: Since its casual discovery and implication as a human pathogen that
      provokes transitory aplastic crises and infectious erythema, the B19 parvovirus
      has been related to a wide spectrum of diseases. To better understand this
      clinical diversity, we reviewed the cases of a serology positive infants admitted
      to the hospital. PATIENTS AND METHODS: From January 1992 to June 1995, all
      clinical charts were reviewed and we obtained 15 patients that had positive IgM
      antibodies by immunoenzyme assay. RESULTS: The mean age was 12.2 months. No sex
      differences were seen. The incidence was higher in winter months. Over 50% of the
      patients belong to the last year studied. Clinical findings included 5 cases of
      arthritis (one juvenile rheumatoid arthritis, one polyarticular syndrome and 3
      nonspecific forms), hematology disturbances in 5 cases (1 case of
      erythrophagocytosis, 1 of thrombocytopenic purpura, 2 of anemia and 1 chronic
      neutropenia), 3 cases of febrile syndrome, 1 liver dysfunction, and 1
      neuromyelitis. Complementary exams were not significant and follow-up in all
      infants was satisfactory. CONCLUSIONS: The B19 parvovirus, a poorly understood
      virus, is related to many clinical situations where is true significance remains
      unknown.

PMID- 9575117
TI  - [Neuroblastoma in children under than 1 year of age].
AB  - OBJECTIVE: Our objective was to carry out a prospective multicenter study of
      neuroblastoma patients diagnosed between 0 and 12 months of age. PATIENTS AND
      METHODS: Diagnostic procedures included histology, catecholamine excretion, bone
      marrow cytology and MIBG-scan. Staging was evaluated according to the INSS
      classification. After 1992, Simada criteria were used and also N-myc
      amplification, DNA index and P-glycoprotein determinations in tumoral tissue. The
      surgical technique employed and complications derived from it were also
      evaluated. The patients were treated according to stage with multicenter Spanish
      protocols N-I-87 and N-II-92. Overall survival and event free survival were
      calculated by actuarial methods. RESULTS: Between October 1987 and June 1992, a
      total of 140 infants less than one year of age were registered and diagnosed of
      neuroblastoma, representing 40% of all neuroblastoma cases. Median age was 0.3
      years and 73% were less than 6 months of age at diagnosis. The most frequent
      stage was 1 (35%) followed by 4-S (20%). The frequency of unfavorable prognostic
      factors was the following: LDH (21%), NSE (14%), ferritin (18%), Shimada (7%),
      DNA (35%), NMA (3%), TrakA (23%), P-glycoprotein (19%). Surgery was performed in
      133 children: total resection was reported in 94 and > 90% in another 22 cases.
      Complications attributed to surgery occurred in 12% of the cases. Chemotherapy
      was given in 73 cases and radiotherapy in 7. The five year total survival is 91%
      and the event free survival 88%. Survival by stages: Stage 1 = 91%, stage 2A =
      88%, stage 2B = 100%, stage 3 = 84%, stage 4 = 56% and stage 4-S = 100%.
      CONCLUSIONS: 1) The majority of neuroblastoma cases in infants less than one year
      old are diagnosed before six months of age. 2) For this age group stages 1 and 4
      S are the most frequently observed. 3) Unfavorable biological factors are less
      frequent than for children over one year of age and are associated with
      disseminated disease (advanced stage). 4) The outcome is excellent, except for
      stage 4 patients. The cases in stage 1 and 2 may be treated by surgery alone.
      Chemotherapy may be of benefit for stage 3 patients.

PMID- 9575118
TI  - [Accuracy of the methods for height prediction in patients treated for congenital
      primary hypothyroidism].
AB  - OBJECTIVE: The objective of this study was to determine how accurately three
      methods of height prediction (the Bayley-Pinneau, Tanner-Whitehouse Mark 1 and
      Roche-Wainer-Thissen methods) estimate adult height in a group of 17 girls and 7
      boys treated for congenital primary hypothyroidism. PATIENTS AND METHODS: The
      patients were diagnosed at a mean chronological age of 1.2 years. Their thyroxine
      treatment dose ranged between 3.1 and 8.6 micrograms/kg/day. Height predictions
      at various chronological ages were retrospectively compared to final adult
      height. The first prediction was made at a chronological age of 7.3(1.1) years,
      corresponding to the sixth year of treatment. Heights were expressed in
      centimeters and standard deviation scores (SDS) and related to Tanner
      standardized curves. RESULTS: The final heights reached were significantly higher
      than the target heights (-0.5 (0.7) SDS vs -1.1 (0.9) SDS, p < 0.01). The three
      methods accurately estimated adult height. Tanner and Bayley-Pinneau height
      predictions were similar. The Roche method over-predicted height at all
      chronological ages with a mean error which ranged between +2 (3.2) centimeters
      and +2.8 (2.1) centimeters. CONCLUSIONS: 1) The patients who were diagnosed and
      treated early for congenital primary hypothyroidism reach an adult height in the
      normal range, which is probably related to the total recovery of their retarded
      bone age. 2) In this pathological condition, the Bayley-Pinneau and Tanner
      Whitehouse Mark 1 are the most reliable methods of height prediction.

PMID- 9575119
TI  - [Hypoxic-ischemic coma in children. Factors related to the prognosis].
AB  - OBJECTIVE: The purpose of this study was to analyze the etiology, evolution and
      predictive value of clinical variables and complementary explorations in children
      admitted to a PICU with hypoxic-ischemic coma. PATIENTS AND METHODS: A
      retrospective review (1991-1996) of 24 children with hypoxic-ischemic coma
      admitted to the pediatric ICU of a reference hospital was performed. Clinical
      data on admission and results of complementary explorations (EEG and neuroimaging
      techniques) were collected and the findings compared according to the evolution
      and underlying pathophysiological mechanism. RESULTS: Non-reactive and dilated
      pupils, existence of neurohypophyseal disorders and isoelectric EEGs were
      exclusively found in dead patients. A score of 3-4 on the Glasgow Coma Score was
      obtained more frequently in groups with the worse evolution (exitus and surviving
      with sequelae), as well as positive findings with neuroimaging techniques and the
      appearance of seizures, though without meaningful differences. More significant
      was the existence of associated problems, which was more frequent in groups with
      a negative evolution. The differences among the pathophysiological groups were
      not meaningful. Global mortality in the series studied was 41.6%, with 29.2% of
      the survivors having neurological sequelae and 29.2% being healthy. CONCLUSIONS:
      Hypoxic-ischemic coma in children has a high mortality and morbility. The
      prognosis for each patient is based on the clinical facts and complementary
      explorations. No isolated data allows the establishment of the final outcome with
      certainty.

PMID- 9575120
TI  - [Prognostic value and accuracy of crisis indicators in severe asthma].
AB  - OBJECTIVE: The objective of this study was to evaluate the predictive index of
      several scores such as the Scarfone score. Wood-Downes modified by Ferres and
      transcutaneous oxygen saturation. (Stc,O2) for the detection of severe asthma
      exacerbations. PATIENTS AND METHODS: A transverse study design was used. Sixty
      patients under 15 years of age admitted consecutively with acute asthma were
      included in the study. We evaluated the relation (Pearson "r" correlation),
      precision (sensibility and specificity) and odds ratio (logistic regression) of
      the scores and Stc,O2 with the number of salbutamol doses required by the
      patients during their hospitalization. RESULTS: The number of doses of
      bronchodilator needed to revert acute asthma relates to the hospital stay (r =
      0.74, p < 0.0002), to all the scores taken into account (r > 0.65, 0 < 0.001) an
      to the Stc,O2 (r = -0.66, p < 0.001). The evaluated scores are prognostic factors
      for severe acute asthma, while heart rate and respiratory rate did not predict
      severe acute asthma. CONCLUSIONS: We have to identify, treat and classify as
      having severe acute asthma those patients who after receiving three doses of
      inhaled bronchodilator show a Scarfone score over 10 or a Ferres score over 8,
      these being situations related to an increased need of bronchodilator therapy and
      a longer hospital stay.

PMID- 9575121
TI  - [Acquired aphasic epilepsy (Landau-Kleffner syndrome). Report of 10 cases].
AB  - OBJECTIVE: The association of a language disorder with epilepsy is observed in
      some circumstance, with or without a causal relationship. In Landau-Kleffner
      syndrome (LKS), it is estimated that the aphasia is directly caused by epileptic
      discharges in language areas. PATIENTS AND METHODS: Ten children with LKS are
      studied. The clinical and electroencephalographic characteristics in these ten
      cases were analyzed. RESULTS: Aphasia was present between 3 years and 6 years 5
      months of age (X: 4 years 8 months) in a progressive form in 8 cases and abruptly
      in 2 cases. The epileptic seizures present in nine children began between 22
      months and 7 years 3 months of age (X: 4 years 1 month). Focal, multifocal and/or
      generalized discharges, unstable and variable, were frequently noted during awake
      state EEG records and on EEGs during the sleep state in four children continuous
      spike waves during 75-80% of slow sleep were observed. CONCLUSIONS: We discuss
      the importance of the different clinical and EEG findings in the evolution of
      aphasia which condition the longterm prognosis, emphasizing the value of the
      discharges on the sleep EEGs. This suggests that LKS could be the severe form of
      a more widespread age-dependent epileptic syndrome that also includes the CSWS
      (epilepsy with continuous spike and waves during slow sleep) and the atypical
      benign partial epilepsy. Three syndromes have cognitive and behavioral
      manifestations and continuous spike waves during slow sleep.

PMID- 9575122
TI  - [The environment in neonatal intensive care units].

PMID- 9575123
TI  - [Vertical transmission of hepatitis C virus].
AB  - OBJECTIVE: The objectives of this study were to know the prevalence of hepatitis
      C virus (HCV) in a population of pregnant women, to evaluate the vertical
      transmission rates of HCV in a prospective study and to determine the
      repercussions and consequences in children born to infected mothers. PATIENTS AND
      METHODS: A total of 6556 pregnant women were tested for HCV antibodies from
      January 1993 to August 1995. We followed 50 babies born to infected mothers for
      at least 12 months (mean 15 months). Serological assays employed included a
      screening ELISA II confirmed with immunoblot. Viral detection was performed by
      qualitative and quantitative PCR for HCV-RNA. RESULTS: Fifty-nine pregnant women
      were AcHCV(+). This represents a seroprevalence of 0.9%. Of the 50 babies
      followed, 6 were PCR(+) and 44 were PCR(-). The risk of transmission is
      correlated with the titer of HCV-RNA in the mother. All mothers of infected
      babies were HIV (-). CONCLUSIONS: The rate of prevalence in our pregnant women
      population is 0.9%. We found a vertical transmission rate of 12%. The high serum
      HCV-RNA titers in the mothers are a risk factor of transmission of HCV. The
      viremia in the children does not predict the apparition of the clinical disease,
      although they can exhibit intermittent increases of transaminases.

PMID- 9575124
TI  - [Transposition of the great arteries and pulmonary hypertension: inhaled nitric
      oxide as a therapy and early surgical correction].
AB  - OBJECTIVE: The objective of this study is to present our preliminary experience
      with pulmonary hypertension inhaled nitric oxide therapy with two newborns
      presenting with transposition of the great arteries, as well as the usefulness of
      the Doppler in pulmonary hypertension diagnosis. PATIENTS AND METHODS: Revision
      of the variations of the hypoxic parameters according to the therapy and revision
      of the diagnostic procedures in both cases was carried out. RESULTS: Nitric oxide
      therapy was followed by an evident improvement of the hypoxia and the patient's
      hemodynamic stabilization, which allowed surgical correction in optimal
      conditions. The ductal flow pattern allowed recognition of the presence of
      pulmonary hypertension. CONCLUSIONS: Inhaled nitric oxide must be taken into
      account as a very useful option in the treatment of this kind of patient and the
      Doppler examination allows the evaluation of the presence of pulmonary
      hypertensions.

PMID- 9575125
TI  - [Schamberg's disease. An infrequent occurrence in pediatrics].

PMID- 9575127
TI  - [Hydrocele and testicular tumors in infancy].

PMID- 9575126
TI  - [Syndrome of contiguous gene deletions in Xp-21 (deficiency of the glycerol
      kinase complex). The association of Duchenne muscular dystrophy, glycerol kinase
      deficiency and congenital suprarenal hypoplasia].

PMID- 9575128
TI  - [High risk cerebellar medulloblastoma: the use of high doses of chemotherapy].

PMID- 9575129
TI  - [An increase in incidence of scarlet fever].

PMID- 9575130
TI  - [Hinman syndrome: an entity to keep in mind].

PMID- 9575131
TI  - [Congenital oculomotor apraxia and partial deficiency of pyruvate carboxylase].

PMID- 9575132
TI  - Failure to differentiate Cryptosporidium parvum from C. meleagridis based on PCR
      amplification of eight DNA sequences.
AB  - In order to determine the specificities of PCR-based assays used for detecting
      Cryptosporidium parvum DNA, eight pairs of previously described PCR primers
      targeting six distinct regions of the Cryptosporidium genome were evaluated for
      the detection of C. parvum, the agent of human cryptosporidiosis, and C. muris,
      C. baileyi, and C. meleagridis, three Cryptosporidium species that infect birds
      or mammals but are not considered to be human pathogens. The four Cryptosporidium
      species were divided into two groups: C. parvum and C. meleagridis, which gave
      the same-sized fragments with all the reactions, and C. muris and C. baileyi,
      which gave positive results with primer pairs targeting the 18S rRNA gene only.
      In addition to being genetically similar at each of the eight loci analyzed by
      DNA amplification, C. parvum and C. meleagridis couldn't be differentiated even
      after restriction enzyme digestion of the PCR products obtained from three of the
      target genes. This study indicates that caution should be exercised in the
      interpretation of data from water sample analysis performed by these methods,
      since a positive result does not necessarily reflect a contamination by the human
      pathogen C. parvum.

PMID- 9575133
TI  - Fluorescent pseudomonad pyoverdines bind and oxidize ferrous ion.
AB  - Major pyoverdines from Pseudomonas fluorescens 2-79 (Pf-B), P. aeruginosa ATCC
      15692 (Pa-C), and P. putida ATCC 12633 (Pp-C) were examined by absorption and
      fluorescence spectroscopic techniques to investigate the interaction between
      ferrous ion and the pyoverdine ligand. At physiological pH, ferrous ion quenched
      the fluorescence of all three pyoverdines much faster than ferric ion did. Also,
      increased absorbance at 460 nm was observed to be much faster for Fe2+ 
      pyoverdine than for Fe3+ -pyoverdine. At pH 7.4, about 90% of Fe3+ was bound by
      pyoverdine Pa-C after 24 h whereas Fe2+ was bound by the pyoverdine completely in
      only 5 min. The possibility that Fe2+ underwent rapid autoxidation before being
      bound by pyoverdine was considered unlikely, since the Fe2+ concentration in
      pyoverdine-free samples remained constant over a 3-min period at pH 7.4.
      Incubating excess Fe2+ with pyoverdine in the presence of 8-hydroxyquinoline, an
      Fe3+ -specific chelating agent, resulted in the formation of a Fe3+ 
      hydroxyquinoline complex, suggesting that the iron in the Fe2+ -pyoverdine
      complex existed in the oxidized form. These results strongly suggested that
      pyoverdines bind and oxidize the ferrous ion.

PMID- 9575134
TI  - Analysis of stable low-molecular-weight RNA profiles of members of the family
      Rhizobiaceae.
AB  - Staircase electrophoresis in polyacrylamide gels was used to analyze the stable
      low-molecular-weight (LMW) RNA profiles of 24 type strains belonging to the
      family Rhizobiaceae. This new electrophoretic technique results in good
      separation of the molecules forming the LMW RNA profiles. Differences in the
      number and distribution of the RNA bands in these profiles allowed us to identify
      differences among the 24 strains assayed. Species assignments based on LMW RNAs
      proved to be consistent with the established taxonomic classification. Analysis
      of the data obtained and the corresponding dendrograms revealed relationships
      between genera and species; these relationships were essentially the same as
      those obtained with other techniques, such as DNA hybridization and 16S rRNA
      sequencing. Use of the technique described here, with which it is possible to
      analyze a large number of strains in a short time, permits rapid identification
      of species belonging to the family Rhizobiaceae and should in the future
      facilitate biodiversity studies and detection of new species.

PMID- 9575135
TI  - Chemotaxis of pathogenic Vibrio strains towards mucus surfaces of gilt-head sea
      bream (Sparus aurata L.).
AB  - Vibrio anguillarum and Vibrio alginolyticus exhibited significant adhesion to and
      chemotactic abilities towards mucus collected from the skin, gills, and intestine
      of gilt-head sea bream. Quadratic polynomial models for chemotaxis designed to
      estimate the influence of temperature demonstrated a differential bacterial
      chemotaxis depending of the source of the mucus, with the chemotaxis towards
      intestinal mucus being the least influenced.

PMID- 9575136
TI  - Autoregulatory mechanisms in protein-tyrosine kinases.

PMID- 9575137
TI  - Distinct nuclear localization and activity of tissue transglutaminase.
AB  - Tissue transglutaminase is a calcium-dependent transamidating enzyme that has
      been postulated to play a role in the pathology of expanded CAG repeat disorders
      with polyglutamine expansions expressed within the affected proteins. Because
      intranuclear inclusions have recently been shown to be a common feature of many
      of these codon reiteration diseases, the nuclear localization and activity of
      tissue transglutaminase was examined. Subcellular fractionation of human
      neuroblastoma SH-SY5Y cells demonstrated that 93% of tissue transglutaminase is
      localized to the cytosol. Of the 7% found in the nucleus, 6% copurified with the
      chromatin-associated proteins, and the remaining 1% was in the nuclear matrix
      fraction. In situ transglutaminase activity was measured in the cytosolic and
      nuclear compartments of control cells, as well as cells treated with the calcium
      mobilizing agent maitotoxin to increase endogenous tissue transglutaminase
      activity. These studies revealed that tissue transglutaminase was activated in
      the nucleus, a finding that was further supported by cytochemical analysis.
      Immunofluorescence studies revealed that nuclear proteins modified by
      transglutaminase exhibited a discrete punctate, as well as a diffuse staining
      pattern. Furthermore, different proteins were modified by transglutaminase in the
      nucleus compared with the cytosol. The results of these experiments clearly
      demonstrate localization of tissue transglutaminase in the nucleus that can be
      activated. These findings may have important implications in the formation of the
      insoluble nuclear inclusions, which are characteristic of codon reiteration
      diseases such as Huntington's disease and the spinocerebellar ataxias.

PMID- 9575138
TI  - p53 inhibits hypoxia-inducible factor-stimulated transcription.
AB  - p53 is required for hypoxia-induced apoptosis in vivo, although the mechanism by
      which this occurs is not known. Conversely, induction of the hypoxia-inducible
      factor-1 (HIF-1) transactivator stimulates transcription of a number of genes
      crucial to survival of the hypoxic state. Here we demonstrate that p53 represses
      HIF-1-stimulated transcription. Although higher levels of p53 are required to
      inhibit HIF than are necessary to transcriptionally activate p53 target genes,
      these levels of p53 are similar to those that stimulate cleavage of poly(ADP
      ribose) polymerase, an early event in apoptosis. Transfection of full-length p300
      stimulates both p53-dependent and HIF-dependent transcription but does not
      relieve p53-mediated inhibition of HIF. In contrast, a p300 fragment, which binds
      to p53 but not to HIF-1, prevents p53-dependent repression of HIF activity.
      Transcriptionally inactive p53, mutated in its DNA binding domain, retains the
      ability to block HIF transactivating activity, whereas a transcriptionally
      inactive double point mutant defective for p300 binding does not inhibit HIF.
      Finally, depletion of doxorubicin-induced endogenous p53 by E6 protein attenuates
      doxorubicin-stimulated inhibition of HIF, suggesting that a p53 level sufficient
      for HIF inhibition can be achieved in vivo. These data support a model in which
      stoichiometric binding of p53 to a HIF/p300 transcriptional complex mediates
      inhibition of HIF activity.

PMID- 9575139
TI  - D-peptide ligands for the co-chaperone DnaJ.
AB  - The molecular chaperone DnaK, the Hsp70 homolog of Escherichia coli, binds
      hydrophobic polypeptide segments in extended conformation. The co-chaperone DnaJ
      (Hsp40) has been reported to bind native and denatured proteins as well as
      peptides. We tested pseudo-peptides of D-amino acids as ligands for both
      chaperones. In comparison to the parent all-L peptide, these mimetics had either
      enantiomorphic side chain positions combined with retained main chain direction
      (normal all-D peptide) or unchanged side chain topology together with reverse
      direction of the peptide backbone (retro all-D peptide). The peptides were
      labeled with acrylodan (a), and their binding to DnaK and DnaJ was monitored by
      the accompanying increase in fluorescence intensity. The parent all-L peptide a
      CALLLSAARR bound to both DnaK (Kd = 0.1 microM) and DnaJ (Kd = 9.2 microM). In
      contrast, the normal all-D and retro all-D peptides did not bind to DnaK; they
      bound, however, to DnaJ with Kd values of 6.8 microM and 0.9 microM,
      respectively. The emission spectra of the DnaJ-bound peptides suggests that DnaJ
      bound both D-peptides with the same main chain direction as L-peptides. Binding
      of the normal all-D and all-L peptides inhibited the DnaJ-induced stimulation of
      DnaK ATPase. However, binding of the retro all-D analog to DnaJ did not impair
      the stimulation, indicating the existence of separate binding sites for peptides
      and DnaK.

PMID- 9575140
TI  - Xanthurenic acid induces gametogenesis in Plasmodium, the malaria parasite.
AB  - A small, heat stable chromophore extracted from mosquitoes has recently been
      implicated as the signal that induces mating of Plasmodium, the malaria parasite.
      We have used high resolution electrospray mass spectrometry to determine that
      this gamete activation factor (GAF) has a m/z = 205.0450, suggesting a molecular
      species composition of C10H7NO4. Xanthurenic acid (XA), a product of tryptophan
      catabolism, was determined to have an elemental composition, ultraviolet
      absorbance maxima, and mass spectrum consistent with those characteristics of
      GAF. XA activated gametogenesis of Plasmodium gallinaceum and P. falciparum in
      vitro at concentrations lower than 0.5 microM in saline buffered to pH 7.4. A
      structural analog of XA, kynurenic acid (C10H6NO3), also activated gametogenesis
      but only at higher concentrations and with less effect. We propose that XA is
      GAF. This is the first evidence that XA has induction activity.

PMID- 9575141
TI  - Cloning and expression in Escherichia coli of the cytochrome c552 gene from
      Thermus thermophilus HB8. Evidence for genetic linkage to an ATP-binding cassette
      protein and initial characterization of the cycA gene products.
AB  - We report sequence of Thermus thermophilus HB8 DNA containing the gene (cycA) for
      cytochrome c552 and a gene (cycB) encoding a protein homologous with one subunit
      of an ATP-binding cassette transporter. The cycA gene encodes a 17-residue N
      terminal signal peptide with following amino acid sequence identical to that
      reported by (Titani, K., Ericsson, L. H., Hon-nami, K., and Miyazawa, T. (1985)
      Biochem. Biophys. Res. Commun. 128, 781-787). A modified cycA was placed under
      control of the T7 promoter and expressed in Escherichia coli. Protein identical
      to that predicted from the gene sequence was found in two heme C-containing
      fractions. Fraction rC552, characterized by an alpha-band at 552 nm, contains
      approximately 60-70% of a protein highly similar to native cytochrome c552 and
      approximately 30-40% of a protein that contains a modified heme. Cytochrome rC552
      is monomeric and is an excellent substrate for cytochrome ba3. Cytochrome rC557
      is characterized by an alpha-band at 557 nm, contains approximately 90% heme C
      and approximately 10% of non-C heme, exists primarily as a homodimer, and is
      essentially inactive as a substrate for cytochrome ba3. We suggest that rC557 is
      a "conformational isomer" of rC552 having non-native, axial ligands to the heme
      iron and an "incorrect" protein fold that is stabilized by homodimer formation.

PMID- 9575142
TI  - Cloning and functional characterization of a Brassica napus transporter that is
      able to transport nitrate and histidine.
AB  - A full-length cDNA for a membrane transporter was isolated from Brassica napus by
      its sequence homology to a previously cloned Arabidopsis low affinity nitrate
      transporter. The cDNA encodes a predicted protein of 589 amino acid residues with
      12 putative transmembrane domains. The transporter belongs to a multigene family
      with members that have been identified in bacteria, fungi, plants, and animals
      and that are able to transport a range of different nitrogen-containing
      substrates, including amino acids, peptides, and nitrate. To identify the
      substrates of this plant gene, we have expressed the protein in Xenopus oocytes.
      The properties of the transporter are consistent with a proton cotransport
      mechanism for nitrate, and the voltage dependence of the Km for nitrate was
      determined. The Km for nitrate was shown to increase from 4 to 14 mM as the
      membrane voltage became more negative from -40 to -180 mV. Oocytes expressing the
      gene could accumulate internal nitrate to concentrations higher than those
      measured in water-injected controls. A range of different substrate molecules for
      the transporter was tested, but of these, histidine gave the largest currents,
      although the affinity was in the millimolar range. The pH dependence of the
      activity of the transporter was different for the substrates, with histidine
      transport favored at alkaline and nitrate at acid external pH. Kinetic analysis
      of the mechanism of histidine transport suggests a cotransport of protons and the
      neutral form of the amino acid, with the Km for histidine decreasing at more
      negative membrane voltages. This gene is the first member of this family of
      transporters for which the transport of two very different types of substrate,
      nitrate and histidine, has been demonstrated.

PMID- 9575143
TI  - Nocodazole inhibits signal transduction by the T cell antigen receptor.
AB  - The potential role of the cytoskeleton in signaling via the T cell antigen
      receptor (TCR) was investigated using pharmacological agents. In Jurkat T cells,
      disruption of the actin-based cytoskeleton with cytochalasin D or disruption of
      the microtubules with colchicine did not affect TCR induction of proximal
      signaling events triggered by CD3 mAb. Polymerized actin and tubulin, therefore,
      were not required for TCR-mediated signal transduction. Nocodazole, however, was
      found to inhibit dramatically TCR signaling, independently of its ability to
      depolymerize microtubules. This effect was TCR-specific, because signaling via
      the human muscarinic acetylcholine receptor 1 in the same cells was unaffected. A
      mechanism for the inhibition of TCR signaling by nocodazole was suggested by in
      vitro assays, which revealed that the drug inhibited the kinase activity of LCK
      and, to a lesser extent, FYN. The kinase activity of ZAP-70 in vitro, however,
      was unaffected. These results, therefore, suggested that nocodazole prevented
      initial phosphorylation of the TCR by LCK after stimulation, and as a result, it
      blocked activation of downstream signaling pathways. Immunofluorescence analyses
      also revealed that nocodazole and the specific SRC-family kinase inhibitor PP1
      delocalized ZAP-70 from its constitutive site at the cell cortex. These effects
      did not require the SH2 domains of ZAP-70. The localization of ZAP-70 to the cell
      cortex is, therefore, regulated by the activity of SRC-family kinases,
      independently of their ability to phosphorylate immunoreceptor tyrosine-based
      activation motifs of the TCR.

PMID- 9575145
TI  - The multisubunit IkappaB kinase complex shows random sequential kinetics and is
      activated by the C-terminal domain of IkappaB alpha.
AB  - The multisubunit IkappaB kinase (IKK) catalyzes the signal-inducible
      phosphorylation of N-terminal serines of IkappaB. This phosphorylation is the key
      step in regulating the subsequent ubiquitination and proteolysis of IkappaB,
      which then releases NF-kappaB to promote gene transcription. As measured by 33P
      incorporation into a GST-IkappaB alpha fusion protein, varying both the
      concentration of GST-IkappaB alpha and [gamma-33P]ATP resulted in a kinetic
      pattern consistent with a random, sequential binding mechanism. Values of 55 nM
      and 7 microM were obtained for the dissociation constants of GST-IkappaB alpha
      and ATP, respectively. The value of alpha, a factor by which binding of one
      substrate changes the dissociation constant for the other substrate, was
      determined to be 0.11. This indicates that the two substrates bind in a
      cooperative fashion. Peptides corresponding to either amino acids 26-42 (N
      terminal peptide) or amino acids 279-303 (C-terminal peptide) of IkappaB alpha
      inhibited the IKK-catalyzed phosphorylation of GST-IkappaB alpha; the C-terminal
      peptide, unexpectedly, was more potent. The inhibition by the C-terminal peptide
      was competitive with respect to GST-IkappaB alpha and mixed with respect to ATP,
      which verified the sequential binding mechanism. The C-terminal peptide was also
      a substrate for the enzyme, and a dissociation constant of 2.9-6.2 microM was
      obtained. Additionally, the N-terminal peptide was a substrate (Km = 140 microM).
      Competitive inhibition of the IKK-catalyzed phosphorylation of the C-terminal
      peptide by the N-terminal peptide indicated that the peptides are phosphorylated
      by the same active site. Surprisingly, the presence of the C-terminal peptide
      greatly accelerated the rate of phosphorylation of the N-terminal peptide as
      represented by a 160-fold increase in the apparent second-order rate constant
      (kcat/Km). These results are consistent with an allosteric site present within
      IKK that recognizes the C terminus of IkappaB alpha and activates the enzyme.
      This previously unobserved interaction with the C terminus may represent an
      important mechanism by which the enzyme recognizes and phosphorylates IkappaB.

PMID- 9575144
TI  - Cytochrome b558/566 from the archaeon Sulfolobus acidocaldarius. A novel highly
      glycosylated, membrane-bound b-type hemoprotein.
AB  - In this study we re-examined the inducible cytochrome b558/566 from the archaeon
      Sulfolobus acidocaldarius (DSM 639), formerly thought to be a component of a
      terminal oxidase (Becker, M., and Schafer, G. (1991) FEBS Lett. 291, 331-335). An
      improved purification method increased the yield of the protein and allowed more
      detailed investigations. Its molecular mass and heme content have been found to
      be 64,210 Da and 1 mol of heme/mol of protein, respectively. It is only
      detectable in cells grown at low oxygen tensions. The composition of the growth
      medium also exerts significant influence on the cytochrome b558/566 content of S.
      acidocaldarius membranes. The cytochrome exhibits an extremely high redox
      potential of +400 mV and shows no CO reactivity; a ligation other than a His/His
      coordination of axial ligands appears likely. It turned out to be highly
      glycosylated (more than 20% of its molecular mass are sugar residues) and is
      probably exposed to the outer surface of the plasma membrane. The sugar moiety
      consists of several O-glycosidically linked mannoses and at least one N
      glycosidically linked hexasaccharide comprising two glucoses, two mannoses, and
      two N-acetyl-glucosamines. The gene of the cytochrome (cbsA) has been sequenced,
      revealing an interesting predicted secondary structure with two putative alpha
      helical membrane anchors flanking the majority of a mainly beta-pleated sheet
      structure containing unusually high amounts of serine and threonine. A second
      gene (cbsB) was found to be cotranscribed. The latter displays extreme
      hydrophobicity and is thought to form a functional unit with cytochrome b558/566
      in vivo, although it did not copurify with the latter. Sequence comparisons show
      no similarity to any entry in data banks indicating that this cytochrome is
      indeed a novel kind of b-type hemoprotein. A cytochrome c analogous function in
      the pseudoperiplasmic space of S. acidocaldarius is discussed.

PMID- 9575146
TI  - nolO and noeI (HsnIII) of Rhizobium sp. NGR234 are involved in 3-O-carbamoylation
      and 2-O-methylation of Nod factors.
AB  - Loci unique to specific rhizobia direct the adjunction of special groups to the
      core lipo-oligosaccharide Nod factors. Host-specificity of nodulation (Hsn) genes
      are thus essential for interaction with certain legumes. Rhizobium sp. NGR234,
      which can nodulate >110 genera of legumes, possesses three hsn loci and secretes
      a large family of Nod factors carrying specific substituents. Among them are 3-O
      (or 4-O)- and 6-O-carbamoyl groups, an N-methyl group, and a 2-O-methylfucose
      residue which may bear either 3-O-sulfate or 4-O (and 3-O)-acetyl substituents.
      The hsnIII locus comprises a nod box promoter followed by the genes
      nodABCIJnolOnoeI. Complementation and mutation analyses show that the disruption
      of any one of nodIJ, nolO, or noeI has no effect on nodulation. Conjugation of
      nolO into Rhizobium fredii extends the host range of the recipient to the non
      hosts Calopogonium caeruleum and Lablab purpureus, however. Chemical analyses of
      the Nod factors produced by the NodI, NolO, and NoeI mutants show that the nolO
      and noeI gene products are required for 3 (or 4)-O-carbamoylation of the
      nonreducing terminus and for 2-O-methylation of the fucosyl group, respectively.
      Confirmation that NolO is a carbamoyltransferase was obtained from analysis of
      the Nod factors produced by R. fredii containing nolO; all are carbamoylated at O
      3 (or O-4) on the nonreducing terminus. Since mutation of both nolO and nodU
      fails to completely abolish production of monocarbamoylated NodNGR factors, it is
      clear that a third carbamoyltransferase must exist. Nevertheless, the
      specificities of the two known enzymes are clearly different. NodU is only able
      to transfer carbamate to O-6 while NolO is specific for O-3 (or O-4) of NodNGR
      factors.

PMID- 9575147
TI  - Differential use of very late antigen-4 and -5 integrins by hematopoietic
      precursors and myeloma cells to adhere to transforming growth factor-beta1
      treated bone marrow stroma.
AB  - The very late antigen (VLA)-4 and VLA-5 integrins mediate hematopoietic
      progenitor cell attachment to bone marrow (BM) stroma. Transforming growth factor
      beta1 (TGF-beta1) is a cytokine present in the BM microenvironment that has been
      shown to regulate the synthesis of adhesion elements in several cell types. We
      have investigated whether TGF-beta1 action on human BM stromal cells affected the
      adhesion of progenitor cells involving integrins VLA-4 and VLA-5. Two precursor
      cell lines, pre-B Nalm-6 and the multipotential UT-7, attached to untreated
      primary stroma and to the human BM stromal cell line Str-5 preferentially using
      VLA-4. However, treatment of the stroma with TGF-beta1 resulted in a significant
      reduction in the participation of VLA-4 in mediating precursor cell adhesion to
      stroma and a concomitant increase in the utilization of VLA-5. This effect was
      not exclusive of normal BM stroma. Treatment with TGF-beta1 of stroma from
      multiple myeloma BM samples produced a substantial increase in VLA-5 use by the
      myeloma cell line NCI-H929 to adhere to this stroma. The differential use of VLA
      4 and VLA-5 correlated with an increase in fibronectin surface expression by
      stromal cells in response to TGF-beta1. Adhesion assays to purified fibronectin
      using Nalm-6 cells showed a predominant utilization of VLA-4 at low
      concentrations of this ligand, whereas higher concentrations resulted in a
      preferential use of VLA-5. These results indicate that regulation of fibronectin
      expression on BM stromal cells by TGF-beta1 results in a modulation of the
      pattern of integrins used by the precursor and myeloma cells to adhere to BM
      stroma, which could have important consequences on the proliferation and
      differentiation of hematopoietic precursor cells as well as on the localization
      and growth of myeloma cells.

PMID- 9575148
TI  - Insulin receptor-mediated dissociation of Grb2 from Sos involves phosphorylation
      of Sos by kinase(s) other than extracellular signal-regulated kinase.
AB  - The Ras signaling pathway is rapidly activated and then down-regulated following
      stimulation of multiple cell-surface receptors including the insulin receptor
      (IR). Much recent attention has focused on elucidating the mechanism of Ras
      inactivation following IR engagement. Previous data suggest that IR-mediated
      serine/threonine phosphorylation of the Ras guanine nucleotide exchange factor
      Sos correlates with its decreased affinity for the adapter protein Grb2. This
      phosphorylation-induced disassembly of the Grb2.Sos complex is thought to be
      responsible, at least in part, for diminishing Ras activity in Chinese hamster
      ovary cells. In this report, we confirm the causal relationship between Sos
      phosphorylation and Grb2/Sos dissociation. We then examine several putative
      phosphorylation sites of Sos that could potentially regulate this event. Since a
      number of reports suggest that extracellular signal-regulated kinase (ERK)
      phosphorylates Sos, we generated a Sos mutant lacking all seven canonical
      phosphorylation sites for ERK. This mutant is a poor substrate of activated ERK
      in vitro and fails to undergo a change in its electrophoretic mobility following
      IR stimulation. It is, however, phosphorylated after IR stimulation when
      expressed in Chinese hamster ovary cells. Interestingly, the mutant protein still
      dissociates from Grb2 following insulin stimulation, suggesting that ERK is not
      the kinase responsible for regulating the stability of the Grb2.Sos complex.

PMID- 9575149
TI  - Developmental changes in the glycosylation of glycoprotein hormone free alpha
      subunit during pregnancy.
AB  - Glycoprotein hormone alpha subunit, in its free form (free alpha), is a major
      placental product. Its glycosylation was found to change dramatically during the
      advancement of pregnancy. In this study, we have analyzed these glycosylation
      changes in five normal pregnancies. Binding to Lens culinaris lectin increased
      dramatically in all subjects between weeks 14 and 17 from the last menstrual
      period, indicating more core fucosylation as well as possible changes in
      branching of glycans. Studies using Datura stramonium agglutinin confirmed that
      the type of triantennary branching changed in this period of pregnancy. The
      precise structural nature of these changes was determined by high-pH anion
      exchange chromatography and electrospray ionization mass spectrometry. Amounts of
      core fucosylation and of triantennary glycans increased substantially from early
      to late second trimester, and a shift was observed from 1-->4/1-->3- toward
      predominantly 1-->6/1-->6-branched triantennary structures. The glycosylation
      changes occurred in all five individuals at the same time period in gestation,
      suggesting developmental regulation of N-acetylglucosaminyltransferases IV and V
      and alpha6-fucosyltransferase during normal pregnancy. These enzymatic activities
      also appear to be affected in malignant transformation of the trophoblast. Our
      findings have important implications for the proposed use of specific forms of
      glycosylation as markers for cancer, as the relative amounts of these glycans in
      normal pregnancy will be determined by gestational age.

PMID- 9575150
TI  - Expression of the receptor tyrosine kinase Ret on the plasma membrane is
      dependent on calcium.
AB  - Mutations in the Ret receptor tyrosine kinase are responsible for a variety of
      human syndromes, including multiple endocrine neoplasia 2 and Hirschsprung's
      disease. Ret is expressed as a 150-kDa precursor form in the endoplasmic
      reticulum and a 170-kDa mature form at the plasma membrane. Here we show that
      expression of p170(ret) is dependent on calcium. Depletion of extracellular
      calcium completely blocks p170(ret) expression, which is not caused by a decrease
      in half-life of p170(ret) at the plasma membrane but by a defect in processing of
      p150(ret) into p170(ret). This processing defect can be mimicked by treating the
      cells with thapsigargin, a drug that releases calcium from internal stores,
      indicating that reduction in luminal calcium is responsible for the processing
      defect. We propose that a relatively high concentration of luminal calcium is
      necessary for the proper folding of Ret in the endoplasmic reticulum.

PMID- 9575151
TI  - Diocleinae lectins are a group of proteins with conserved binding sites for the
      core trimannoside of asparagine-linked oligosaccharides and differential
      specificities for complex carbohydrates.
AB  - The seed lectin from Dioclea grandiflora and jack bean lectin concanavalin A
      (ConA) are both members of the Diocleinae subtribe of Leguminosae lectins. Both
      lectins have recently been shown to possess enhanced affinities and extended
      binding sites for the trisaccharide, 3,6-di-O-(alpha-D-mannopyranosyl)-D-mannose,
      which is present in the core region of all asparagine-linked carbohydrates
      (Gupta, D., Oscarson, S., Raju, S., Stanley, P. Toone, E. J. and Brewer, C. F.
      (1996) Eur. J. Biochem. 242, 320-326). In the present study, the binding
      specificities of seven other lectins from the Diocleinae subtribe have been
      investigated by hemagglutination inhibition and isothermal titration
      microcalorimetry (ITC). The lectins are from Canavalia brasiliensis, Canavalia
      bonariensis, Cratylia floribunda, Dioclea rostrata, Dioclea virgata, Dioclea
      violacea, and Dioclea guianensis. Hemagglutination inhibition and ITC experiments
      show that all seven lectins are Man/Glc-specific and have high affinities for the
      core trimannoside, like ConA and D. grandiflora lectin. All seven lectins also
      exhibit the same pattern of binding to a series of monodeoxy analogs and a
      tetradeoxy analog of the trimannoside, similar to that of ConA and D. grandiflora
      lectin. However, C. bonariensis, C. floribunda, D. rostrata, and D. violacea,
      like D. grandiflora, show substantially reduced affinities for a biantennary
      complex carbohydrate with terminal GlcNAc residues, while C. brasiliensis, D.
      guianensis, and D. virgata, like ConA, exhibit affinities for the oligosaccharide
      comparable with that of the trimannoside. Thermodynamic data obtained by ITC
      indicate different energetic mechanisms of binding of the above two groups of
      lectins to the complex carbohydrate. The ability of the lectins to induce
      histamine release from rat peritoneal mast cells is shown to correlate with the
      relative affinities of the proteins for the biantennary carbohydrate.

PMID- 9575152
TI  - Changing residue 338 in human factor IX from arginine to alanine causes an
      increase in catalytic activity.
AB  - This study was designed to identify functionally important factor IX (FIX)
      residues. Using recombinant techniques and cell culture, we produced a mutant FIX
      with arginine at 338 changed to alanine (R338A-FIX). This molecule had
      approximately 3 times greater clotting activity than that of wild type FIX (wt
      FIX) in the activated partial thromboplastin assay. R338A-FIX reacted normally
      with a panel of three FIX specific monoclonal antibodies and migrated on sodium
      dodecyl sulfate-polyacrylamide gels indistinguishably from wt-FIX. Using
      functional assays, we determined that R338A-FIXa's Kd for factor VIIIa (FVIIIa)
      was similar to that of wt-FIXa. Our kinetic analysis, using factor X as
      substrate, indicated that the mutation's major effects were a 3-fold increase in
      kcat and a 2-fold decrease in Km both manifested only in the presence of FVIIIa.
      R338A-FIXa's increased catalytic efficiency did not result from ablation of a
      thrombin sensitive site, reported to occur at arginine 338, since in our assays
      the thrombin inhibitor, hirudin, had no effect on activity of either wt-FIXa or
      R338A-FIXa. R338A-FIXa and wt-FIXa had equal activity, with or without FVIIIa,
      toward the synthetic substrate, methylsulfonyl-D-cyclohexylglycyl-arginine-p
      nitroanilide. Interestingly, R338A-FIXa had reduced affinity for heparin.
      Therefore, we propose that R338A-FIXa's increased activity is not due to an
      allosteric effect on the active site, but that the Arg-338 residue is part of an
      exosite that binds both factor X and the mucopolysaccharide, heparin.

PMID- 9575153
TI  - Serine 13 is the site of mitotic phosphorylation of human thymidine kinase.
AB  - It has been reported that the polypeptide of thymidine kinase type 1 (TK1) from
      human and mouse cells can be modified by phosphorylation. Our laboratory has
      further shown that the level of human TK phosphorylation increases during mitotic
      arrest in different cell types (Chang, Z.-F., Huang, D.-Y., and Hsue, N.-C.
      (1994) J. Biol. Chem. 269:21249-21254). In the present study, we demonstrated
      that a mutation converting Ser13 to Ala abolished the mitotic phosphorylation of
      native TK1 expressed in Ltk- cells. Furthermore, we expressed recombinant
      proteins of wild-type and mutated human TK1 with fused FLAG epitope in HeLa
      cells, and confirmed the occurrence of mitotic phosphorylation on Ser13 of hTK1.
      By using an in vitro phosphorylation assay, it was shown that wild-type hTK1, but
      not mutant TK1(Ala13), could serve as a good substrate for Cdc2 or Cdk2 kinase.
      Coexpression of p21(waf1/cip1), which is a universal inhibitor of Cdk kinases, in
      Ltk- fibroblasts also suppressed mitotic phosphorylation of hTK1 expressed in
      this cell line. Thus, Cdc2 or related kinase(s) is probably involved in mitotic
      phosphorylation on Ser13 of the hTK1 polypeptide. We also found that mutation on
      Ser13 did not affect the functional activity of hTK1. As the sequences around
      Ser13 are highly conserved in vertebrate TK1s, we speculate that phosphorylation
      of Ser13 may play a role in the regulation of TK1 expression in the cell cycle.

PMID- 9575154
TI  - The steroid receptor coactivator-1 contains multiple receptor interacting and
      activation domains that cooperatively enhance the activation function 1 (AF1) and
      AF2 domains of steroid receptors.
AB  - Steroid receptors are ligand-inducible transcription factors, and their
      association with steroid receptor coactivators (SRCs) upon binding to DNA is
      necessary for them to achieve full transcriptional potential. To understand the
      mechanism of SRC-1 action, its ability to interact and enhance the
      transcriptional activity of steroid receptors was analyzed. First, we show that
      SRC-1 is a modular coactivator that possesses intrinsic transcriptional activity
      when tethered to DNA and that it harbors two distinct activation domains, AD1 and
      AD2, needed for the maximum coactivation function of steroid receptors. We also
      demonstrate that SRC-1 interacts with both the amino-terminal A/B or AF1
      containing domain and the carboxyl-terminal D/E or AF2-containing domain of the
      steroid receptors. These interactions are carried out by multiple regions of SRC
      1, and they are relevant for transactivation. In addition to the inherent histone
      acetyltransferase activity of SRC-1, the presence of multiple receptor
      coactivator interaction sites in SRC-1 and its ability to interact with
      components of the basic transcriptional machinery appears to be, at least in
      part, the mechanism by which the individual activation functions of the steroid
      receptors act cooperatively to achieve full transcriptional activity.

PMID- 9575156
TI  - Mechanosensitive ion channels of the archaeon Haloferax volcanii.
AB  - Mechanosensitive (MS) ion channels have been documented in a variety of cells
      belonging to Eukarya and Eubacteria. We report the novel finding of two types of
      MS ion channels in the cell membrane of the halophilic archaeon Haloferax
      volcanii, a member of the Archaea that comprise the third phylogenetic domain.
      The two channels, MscA1 and MscA2, differed in their kinetic properties with
      MscA1 exhibiting more frequent open-closed transitions than MscA2. Both channels
      have large conductances that rectify between -40 mV and +40 mV where the
      conductance of MscA1 ranged from 380 to 680 picosiemens, whereas MscA2 ranged
      from 850 to 490 picosiemens. Both channels were blocked by submillimolar
      gadolinium. In addition, the channels of either membrane vesicles or detergent
      solubilized membrane proteins remained functional upon reconstitution into
      artificial liposomes, a result that indicates that these channels are activated
      by mechanical force transmitted via the lipid bilayer alone. Subsequently a 37
      kDa protein corresponding to the MscA1 channel activity was purified. With the
      possible functional similarity to bacterial MS channels, our finding of MS
      channels in Archaea emphasizes the ubiquity and importance of these channels in
      all domains of the evolutionary tree.

PMID- 9575155
TI  - Characterization of the C-terminal propeptide involved in bacterial wall spanning
      of alpha-amylase from the psychrophile Alteromonas haloplanctis.
AB  - The antarctic psychrophile Alteromonas haloplanctis secretes a Ca2+- and Cl-
      dependent alpha-amylase. The nucleotide sequence of the amy gene and the amino
      acid sequences of the gene products indicate that the alpha-amylase precursor is
      a preproenzyme composed by the signal peptide (24 residues), the mature alpha
      amylase (453 residues, 49 kDa), and a long C-terminal propeptide or secretion
      helper (192 residues, 21 kDa). In cultures of the wild-type strain, the 70-kDa
      precursor is secreted at the mid-exponential phase and is cleaved by a
      nonspecific protease into the mature enzyme and the propeptide. The purified C
      terminal propeptide displays several features common to beta-pleated
      transmembrane proteins. It has no intramolecular chaperone function because
      active alpha-amylase is expressed by Escherichia coli in the absence of the
      propeptide coding region. In E. coli, the 70-kDa precursor is directed toward the
      supernatant. When the alpha-amylase coding region is excised from the gene, the
      secretion helper can still promote its own membrane spanning. It can also accept
      a foreign passenger, as shown by the extracellular routing of a beta-lactamase
      propeptide fusion protein.

PMID- 9575157
TI  - The role of negative superhelicity and length of homology in the formation of
      paranemic joints promoted by RecA protein.
AB  - Escherichia coli RecA protein pairs homologous DNA molecules to form paranemic
      joints when there is an absence of a free end in the region of homologous
      contact. Paranemic joints are a key intermediate in homologous recombination and
      are important in understanding the mechanism for a search of homology. The
      efficiency of paranemic joint formation depended on the length of homology and
      the topological forms of the duplex DNA. The presence of negative superhelicity
      increased the pairing efficiency and reduced the minimal length of homology
      required for paranemic joint formation. Negative superhelicity stimulated joint
      formation by favoring the initial unwinding of duplex DNA that occurred during
      the homology search and was not essential in the maintenance of the paired
      structure. Regardless of length of homology, formation of paranemic joints using
      circular duplex DNA required the presence of more than six negative supercoils.
      Above six negative turns, an increasing degree of negative superhelicity resulted
      in a linear increase in the pairing efficiency. These results support a model of
      two distinct kinds of DNA unwinding occurring in paranemic joint formation: an
      initial unwinding caused by heterologous contacts during synapsis and a later one
      during pairing of the homologous molecules.

PMID- 9575158
TI  - Arterial blood pressure responses to cell-free hemoglobin solutions and the
      reaction with nitric oxide.
AB  - Changes in mean arterial pressure were monitored in rats following 50% isovolemic
      exchange transfusion with solutions of chemically modified hemoglobins. Blood
      pressure responses fall into three categories: 1) an immediate and sustained
      increase, 2) an immediate yet transient increase, or 3) no significant change
      either during or subsequent to exchange transfusion. The reactivities of these
      hemoglobins with nitric monoxide (.NO) were measured to test the hypothesis that
      different blood pressure responses to these solutions result from differences in
      .NO scavenging reactions. All hemoglobins studied exhibited a value of 30 microM
      1 s-1 for both .NO bimolecular association rate constants and the rate constants
      for .NO-induced oxidation in vitro. Only the .NO dissociation rate constants and,
      thus, the equilibrium dissociation constants varied. Values of equilibrium
      dissociation constants ranged from 2 to 14 pM and varied inversely with
      vasopressor response. Hemoglobin solutions that exhibited either transient or no
      significant increase in blood pressure showed tighter .NO binding affinities than
      hemoglobin solutions that exhibited sustained increases. These results suggest
      that blood pressure increases observed upon exchange transfusion with cell-free
      hemoglobin solutions can not be the result of .NO scavenging reactions at the
      heme, but rather must be due to alternative physiologic mechanisms.

PMID- 9575159
TI  - Activation of thrombin-activable fibrinolysis inhibitor requires epidermal growth
      factor-like domain 3 of thrombomodulin and is inhibited competitively by protein
      C.
AB  - Thrombomodulin is a cofactor protein on vascular endothelial cells that inhibits
      the procoagulant functions of thrombin and enhances thrombin-catalyzed activation
      of anticoagulant protein C. Thrombomodulin also accelerates the proteolytic
      activation of a plasma procarboxypeptidase referred to as thrombin-activable
      fibrinolysis inhibitor (TAFI). In this study, we describe structures on
      recombinant membrane-bound thrombomodulin that are required for human TAFI
      activation. Deletion of the N-terminal lectin-like domain and epidermal growth
      factor (EGF)-like domains 1 and 2 had no effect on TAFI or protein C activation,
      whereas deletions including EGF-like domain 3 selectively abolished
      thrombomodulin cofactor activity for TAFI activation. Provided that
      thrombomodulin EGF-like domain 3 was present, TAFI competitively inhibited
      protein C activation catalyzed by the thrombin-thrombomodulin complex. A
      thrombomodulin construct lacking EGF-like domain 3 functioned normally as a
      cofactor for protein C activation but was insensitive to inhibition by TAFI.
      Thus, the anticoagulant and antifibrinolytic cofactor activities of
      thrombomodulin have distinct structural requirements: protein C binding to the
      thrombin-thrombomodulin complex requires EGF-like domain 4, whereas TAFI binding
      also requires EGF-like domain 3.

PMID- 9575160
TI  - Selective uptake of low density lipoprotein-cholesteryl ester is enhanced by
      inducible apolipoprotein E expression in cultured mouse adrenocortical cells.
AB  - Apolipoprotein (apo) E is expressed at high levels by steroidogenic cells of the
      adrenal gland, ovary, and testis. The cell surface location of apoE in
      adrenocortical cells suggests that apoE may facilitate the uptake of lipoprotein
      cholesterol by either the endocytic or the selective uptake pathways, or both. To
      examine these possibilities, the human apoE gene was expressed in murine Y1
      adrenocortical cells under control of an inducible tetracycline-regulated
      promoter. The results show that induction of apoE yielded a 2-2.5-fold increase
      in the uptake of low density lipoprotein-cholesteryl ester (LDL-CE) but had
      little effect on high density lipoprotein-CE uptake. Analysis of lipoprotein
      uptake pathways showed that apoE increased LDL-CE uptake by both endocytic and
      selective uptake pathways. In terms of cholesterol delivery to the adrenal cell,
      the apoE-mediated enhancement of LDL-CE selective uptake was quantitatively more
      important. Furthermore, the predominant effect of apoE expression was on the low
      affinity component of LDL-CE selective uptake. LDL particles incubated with apoE
      expressing cells contained 0.92 +/- 0.11 apoE molecules/apoB after gel filtration
      chromatography, indicating stable complex formation between apoE and LDL. ApoE
      expression by Y1 cells was necessary for enhanced LDL-CE selective uptake. This
      result may indicate an interaction between apoE-containing LDL and cell surface
      apoE. These data suggest that apoE produced locally by steroidogenic cells
      facilitates cholesterol acquisition by the LDL selective uptake pathway.

PMID- 9575161
TI  - Characterization of human hect domain family members and their interaction with
      UbcH5 and UbcH7.
AB  - The hect domain protein family was originally identified by sequence similarity
      of its members to the C-terminal region of E6-AP, an E3 ubiquitin-protein ligase.
      Since the C terminus of E6-AP mediates thioester complex formation with
      ubiquitin, a necessary intermediate step in E6-AP-dependent ubiquitination, it
      was proposed that members of the hect domain family in general have E3 activity.
      The hect domain is approximately 350 amino acids in length, and we show here that
      the hect domain of E6-AP is necessary and sufficient for ubiquitin thioester
      adduct formation. Furthermore, the human genome encodes at least 20 different
      hect domain proteins, and in further support of the hypothesis that hect domain
      proteins represent a family of E3s, several of these are shown to form thioester
      complexes with ubiquitin. In addition, some hect domain proteins interact
      preferentially with UbcH5, whereas others interact with UbcH7, indicating that
      human hect domain proteins can be grouped into at least two classes based on
      their E2 specificity. Since E3s are thought to play a major role in substrate
      recognition, the presence of a large family of E3s should contribute to ensure
      the specificity and selectivity of ubiquitin-dependent proteolytic pathways.

PMID- 9575162
TI  - Receptor subtype-specific regulation of muscarinic acetylcholine receptor
      sequestration by dynamin. Distinct sequestration of m2 receptors.
AB  - Sustained stimulation of muscarinic acetylcholine receptors (mAChRs) and other G
      protein-coupled receptors usually leads to a loss of receptor binding sites from
      the plasma membrane, referred to as receptor sequestration. Receptor
      sequestration can occur via endocytosis of clathrin-coated vesicles that bud from
      the plasma membrane into the cell but may also be accomplished by other, as yet
      ill-defined, mechanisms. Previous work has indicated that the monomeric GTPase
      dynamin controls the endocytosis of plasma membrane receptors via clathrin-coated
      vesicles. To investigate whether mAChRs sequester in a receptor subtype-specific
      manner via dynamin-dependent clathrin-coated vesicles, we tested the effect of
      overexpressing the dominant-negative dynamin mutant K44A on m1, m2, m3, and m4
      mAChR sequestration in HEK-293 cells. The m1, m2, m3, and m4 mAChRs sequestered
      rapidly in HEK-293 cells following agonist exposure but displayed dissimilar
      sequestration pathways. Overexpression of dynamin K44A mutant fully blocked m1
      and m3 mAChR sequestration, whereas m2 mAChR sequestration was not affected.
      Also, m4 mAChRs, which like m2 mAChRs preferentially couple to pertussis toxin
      sensitive G proteins, sequestered in a completely dynamin-dependent manner.
      Following agonist removal, sequestered m1 mAChRs fully reappeared on the cell
      surface, whereas sequestered m2 mAChRs did not. The distinct sequestration of m2
      mAChRs was also apparent in COS-7 and Chinese hamster ovary cells. We conclude
      that the m2 mAChR displays unique subtype-specific sequestration that
      distinguishes this receptor from the m1, m3, and m4 subtypes. These results are
      the first to demonstrate that receptor sequestration represents a new type of
      receptor subtype-specific regulation within the family of mAChRs.

PMID- 9575163
TI  - Dietary supplementation with vitamin E reverses the age-related deficit in long
      term potentiation in dentate gyrus.
AB  - Long term potentiation (LTP) in dentate gyrus is impaired in aged rats, and this
      has been associated with an age-related decrease in membrane arachidonic acid
      concentration. In this study, we considered whether the trigger for this age
      related decrease in arachidonic acid might be increased lipid peroxidation
      stimulated by the proinflammatory cytokine, interleukin-1beta. Groups of aged and
      young rats were fed on a control diet or a diet supplemented with alpha
      tocopherol and assessed for their ability to sustain LTP. Aged rats fed on the
      control diet exhibited an impaired ability to sustain LTP and analysis of tissue
      prepared from these rats exhibited increased interleukin-1beta, increased lipid
      peroxidation, and decreased membrane arachidonic acid concentration compared with
      young rats fed on either diet. Aged rats fed on the supplemented diet sustained
      LTP in a manner indistinguishable from young rats, and the age-related increases
      in interleukin-1beta and lipid peroxidation and the decrease in membrane
      arachidonic acid concentration were all reversed. We propose that interleukin
      1beta may be the trigger that induces these age-related changes and may therefore
      be responsible for the deficit in long term potentiation in aged rats. The
      observation that alpha-tocopherol reverses these changes is consistent with the
      hypothesis that some age-related changes in hippocampus might derive from
      oxidative stress.

PMID- 9575164
TI  - The transferrin receptor cytoplasmic domain determines its rate of transport
      through the biosynthetic pathway and its susceptibility to cleavage early in the
      pathway.
AB  - The soluble human transferrin receptor (TfR) found in blood is the result of a
      proteolytic cleavage occurring in the ectodomain of the receptor close to the
      transmembrane domain at Arg-100. We have discovered another cleavage site between
      Gly-91 and Val-92 even closer to the transmembrane domain. Cleavage at Gly-91
      differs markedly from the normal cleavage site. It occurs when the entire
      cytoplasmic portion or the proximal 31 amino acids of the transmembrane domain
      are deleted. A soluble disulfide-bonded dimer of the TfR is released into the
      medium in contrast to the cleavage at Arg-100 where a dimer lacking intersubunit
      disulfide bonds is released. Whereas the cleavage at Arg-100 is generated by
      cycling through the endosomal system, pulse-chase experiments indicate that
      cleavage at Gly-91 occurs predominantly during the biosynthesis of the receptor.
      Pulse-chase analysis of the biosynthesis of mutant TfRs that lack the membrane
      proximal cytoplasmic domain show that they exit the endoglycosidase H-sensitive
      compartment at a slower rate than the wild type TfR. These results suggest that
      the cytoplasmic domain influences the trafficking of the TfR either by
      influencing the folding of the ectodomain or by providing a positive signal for
      its transport through the biosynthetic pathway.

PMID- 9575165
TI  - Structure-function relationships among ryanodine derivatives. Pyridyl ryanodine
      definitively separates activation potency from high affinity.
AB  - Ryanodine derivatives are differentially effective on the two limbs of the
      ryanodine concentration-effect curve. This study comparing ryanodine, ryanodol,
      and pyridyl ryanodine and nine C10Oeq esters of them focuses on structure
      function relations underlying their differential effectiveness. Ryanodol and
      pyridyl ryanodine had significantly lower affinities than ryanodine, but their
      EC50act values (concentration of ryanoid that induces one-half of full efficacy),
      potencies, and efficacies were not diminished in like fashion. Ryanodine and
      ryanodol were partial agonists, whereas pyridyl ryanodine was a full agonist,
      having a diminished deactivation potency. C10Oeq esterifications enhanced
      affinities and efficacies of the base ryanoids. The C10-Oeq ester derivatives of
      ryanodine and pyridyl ryanodine, but not those of ryanodol, lost their capacity
      to deactivate RyR1s. Thus, affinity differences among ryanoids clearly do not
      predicate functional differences as regards activation of Ca2+ release channels.
      The pyrrole carboxylate on the C3 of ryanodine is dispensable to ryanoid
      activation of Ca2+ release channels. Ryanodol lacks this ring, but it
      nevertheless effects substantial activation. Moreover, its C10-Oeq esters display
      full efficacy. The increased ability of all the C10-Oeq derivatives to release
      Ca2+ from the vesicles strengthens their role in directly impeding deactivation
      of RyR1, perhaps by interaction with some component within the transmembrane
      ionic flux pathway.

PMID- 9575166
TI  - In vivo 13C NMR measurements of hepatocellular tricarboxylic acid cycle flux.
AB  - A combined isotopic steady state and in vivo isotopic non-steady state analysis
      was used to calculate tricarboxylic acid cycle flux in livers of anesthetized
      rats infused with ethanol. In vivo 13C NMR spectroscopy was used to non
      invasively observe label turnover of [4-13C]glutamate, [4-13C]glutamine, and [2
      13C]glutamate/glutamine in liver following a bolus intravenous infusion of [2
      13C]ethanol. The isotopic steady state analysis of [2-13C], [3-13C], and [4
      13C]glutamate isotopomers (Malloy, C. R., Sherry, A. D., and Jeffrey, F. M. H.
      (1988) J. Biol. Chem. 263, 6964-6971) in liver extracts was used to indirectly
      calculate the anaplerotic flux (0.90 +/- 0.07 x citrate synthase flux) and [2
      13C]acetyl-CoA fractional enrichment (51.4 +/- 3.4%). The [4-13C]glutamate, [4
      13C]glutamine, and [2-13C]glutamate fractional enrichments determined in liver
      extracts were 23.0 +/- 1.1, 17.2 +/- 1.5, and 7.7 +/- 0.5%, respectively. These
      data in addition to blood [2-13C]acetate and [4-13C]glutamine enrichment time
      course data were used in conjunction with a metabolic steady state mathematical
      analysis designed to account for liver glutamate and glutamine label dilution as
      a consequence of glutamine exchange with blood to calculate the tricarboxylic
      acid (tca) cycle flux (Vtca = 0.33 +/- 0.09 micromol/g wet weight/min) in liver.
      In summary, It is possible to detect 13C labeling of glutamate and glutamine in
      liver via non-invasive 13C NMR. Additionally, the in vivo 13C labeling kinetics
      of glutamate and glutamine in liver and glutamine in blood may be used to
      calculate the liver tricarboxylic acid cycle flux.

PMID- 9575167
TI  - Activation of phospholipase D by phosphatidic acid. Enhanced vesicle binding,
      phosphatidic acid-Ca2+ interaction, or an allosteric effect?
AB  - The activity of bacterial phospholipase D (PLD), a Ca2+-dependent enzyme, toward
      phosphatidylcholine bilayers was enhanced 7-fold by incorporation of 10 mol %
      phosphatidic acid (PA) in the vesicle bilayer. Addition of other negatively
      charged lipids such as phosphatidylinositol, phosphatidylmethanol, and oleic acid
      either inhibited or had no effect on enzyme activity. Only negatively charged
      lipids with a free phosphate group, phosphatidylinositol 4-phosphate and lyso-PA,
      had the same effect as PA on enzyme activity. Changes in vesicle curvature and
      fusion were not the reason for PA activation; rather, a metal ion-induced lateral
      segregation of PA in the vesicle bilayer correlated with PLD activation.
      Significant PA activation was also observed with monomer phosphatidylcholine
      substrate upon the addition of PA vesicles. The PA activation was caused by
      Ca2+.PA interacting with PLD at an allosteric site other than active site.

PMID- 9575168
TI  - MyD88, an adapter protein involved in interleukin-1 signaling.
AB  - MyD88 has a modular organization, an N-terminal death domain (DD) related to the
      cytoplasmic signaling domains found in many members of the tumor necrosis factor
      receptor (TNF-R) superfamily, and a C-terminal Toll domain similar to that found
      in the expanding family of Toll/interleukin-1-like receptors (IL-1R). This dual
      domain structure, together with the following observations, supports a role for
      MyD88 as an adapter in IL-1 signal transduction; MyD88 forms homodimers in vivo
      through DD-DD and Toll-Toll interactions. Overexpression of MyD88 induces
      activation of the c-Jun N-terminal kinase (JNK) and the transcription factor NF
      kappaB through its DD. A point mutation in MyD88, MyD88-lpr (F56N), which
      prevents dimerization of the DD, also blocks induction of these activities. MyD88
      induced NF-kappaB activation is inhibited by the dominant negative versions of
      TRAF6 and IRAK, which also inhibit IL-1-induced NF-kappaB activation.
      Overexpression of MyD88-lpr or MyD88-Toll (expressing only the Toll domain) acted
      to inhibit IL-1-induced NF-kappaB and JNK activation in a 293 cell line
      overexpressing the IL-1RI. MyD88 coimmunoprecipitates with the IL-1R signaling
      complex in an IL-1-dependent manner.

PMID- 9575169
TI  - A single position in the third transmembrane domains of the human B1 and B2
      bradykinin receptors is adjacent to and discriminates between the C-terminal
      residues of subtype-selective ligands.
AB  - In order to identify agonist- and antagonist-binding epitopes in the human B1 and
      B2 bradykinin (BK) receptors, we exploited the ability of these receptors to
      discriminate between peptide ligands that differ only by the absence (B1) and
      presence (B2) of a C-terminal Arg. This was done by constructing chimeric
      proteins in which specific domains were exchanged between these receptors as
      recently described by us (Leeb, T., Mathis, S. A., and Leeb-Lundberg, L. M. F.
      (1997) J. Biol. Chem. 272, 311-317). The constructs were then expressed in HEK293
      and A10 cells and assayed by radioligand binding and by agonist-stimulated
      inositol phospholipid hydrolysis and intracellular Ca2+ mobilization.
      Substitution of the third transmembrane domain (TM-III) of the B1 receptor in the
      B2 receptor (B2(B1III)) dramatically reduced the affinities of B2-selective
      peptide ligands including both the agonist BK and the antagonist NPC17731. High
      affinity binding of both ligands to B2(B1III) was fully regained when one
      residue, Lys111, in TM-III of this chimera was replaced with the corresponding
      wild-type (WT) B2 receptor residue, Ser (B2(B1IIIS111)). Replacement of Ser111
      with Lys in the WT B2 receptor decreased the affinities of BK and NPC17731 and
      increased the affinity of the B1-selective des-Arg10 analog of NPC17731,
      NPC18565. The results show that the C-terminal residue of peptide agonists and
      antagonists when bound to the B2 receptor is adjacent to Ser111 in the receptor.
      A Lys at this position, as is the case in the WT B1 receptor, provides a positive
      charge that repels the C-terminal Arg in B2-selective peptides and attracts the
      negative charge of the C terminus of B1-selective peptides, which lack the C
      terminal Arg. Therefore, the residues at this one single position are crucial in
      determining the peptide selectivity of B1 and B2 BK receptors.

PMID- 9575170
TI  - Inhibitors of protein phosphatase 1 and 2A differentially regulate the expression
      of inducible nitric-oxide synthase in rat astrocytes and macrophages.
AB  - Nitric oxide produced by inducible nitric-oxide synthase (iNOS) in different
      cells including brain cells in response to proinflammatory cytokines plays an
      important role in the pathophysiology of stroke and other neurodegenerative
      diseases. The present study underlines the importance of protein phosphatase (PP)
      1 and 2A in the regulation of the differential expression of iNOS in rat primary
      astrocytes and macrophages. Compounds (calyculin A, microcystin, okadaic acid,
      and cantharidin) that inhibit PP 1 and 2A were found to stimulate the
      lipopolysaccharide (LPS)- and cytokine-mediated expression of iNOS and production
      of NO in rat primary astrocytes and C6 glial cells. However, these inhibitors
      inhibited the LPS- and cytokine-mediated expression of iNOS and production of NO
      in rat resident macrophages and RAW 264.7 cells. Similarly, okadaic acid, an
      inhibitor of PP 1/2A, stimulated the iNOS promoter-derived chloramphenicol
      acetyltransferase activity in astrocytes and inhibited the iNOS promoter-derived
      chloramphenicol acetyltransferase activity in macrophages, indicating that
      okadaic acid also differentially regulates the transcription of the iNOS gene in
      astrocytes and macrophages. The observed stimulation of the expression of iNOS in
      astrocytes and the inhibition of the expression of iNOS in macrophages with the
      inhibition of PP 1/2A activity clearly delineate a novel role of PP 1/2A in the
      differential regulation of iNOS in rat astrocytes and macrophages. Because the
      activation of NF-kappaB is necessary for the induction of iNOS and the expression
      of tumor necrosis factor (TNF)-alpha also depends on the activation of NF-kappaB,
      we examined the effect of okadaic acid on the LPS-mediated activation of NF
      kappaB and production of TNF-alpha in rat primary astrocytes and macrophages.
      Interestingly, in both cell types, okadaic acid stimulated the LPS-mediated DNA
      binding as well as transcriptional activity of NF-kappaB and production of TNF
      alpha. This study suggests that the stimulation of iNOS expression in astrocytes
      by inhibitors of PP 1/2A is possibly due to the stimulation of NF-kappaB
      activation; however, activation of NF-kappaB is not sufficient for the induction
      of iNOS in macrophages and that apart from NF-kappaB some other signaling
      pathway(s) sensitive to PP 1 and/or PP 2A is/are possibly involved in the
      regulation of iNOS in macrophages. This differential induction of iNOS as
      compared with similar activation of NF-kappaB by inhibitors of PP 1/2A indicates
      the involvement of different intracellular signaling events for the induction of
      iNOS in two cell types of the same animal species.

PMID- 9575171
TI  - Allosteric regulation of pyruvate kinase M2 isozyme involves a cysteine residue
      in the intersubunit contact.
AB  - Pyruvate kinase M2 isozyme mutants with amino acid substitutions in the subunit
      interface were prepared and characterized. The substitutions were made in the
      allosteric M2 isozyme by the corresponding residues of the nonallosteric M1
      isozyme to identify the residue involved in the allosteric effects. The
      replacement of Cys-423 by Leu led to substantial loss of both homotropic and
      heterotropic allosteric effects while the substitutions at Phe-389, Arg-398, Ala
      401, Pro-402, Thr-408, and Ile-427 did not. The altered kinetic properties of the
      Cys-423-substituted mutant resulted from the shift of the allosteric transition
      toward the active R-state since the mutant exhibits the allosteric properties in
      the presence of an allosteric inhibitor, L-phenylalanine. The inverse correlation
      between the hydrophobicity of residue 423 and the extent of stabilization of the
      R-state was found by analysis of mutants with un-ionizable amino acids at
      position 423. Furthermore, the modification of Cys-423 with methyl
      methanethiosulfonate led to a shift of the allosteric transition toward the R
      state, probably the result of increased hydrophobicity of the residue. These
      results suggest that Cys-423 is involved in the allosteric regulation of the
      enzyme through hydrophobic interactions.

PMID- 9575172
TI  - Mutational analysis of invariant arginines in the IIAB(Man) subunit of the
      Escherichia coli phosphotransferase system.
AB  - The mannose transporter of bacterial phosphotransferase system mediates uptake of
      mannose, glucose, and related hexoses by a mechanism that couples translocation
      with phosphorylation of the substrate. It consists of the transmembrane IIC(Man)
      IID(Man) complex and the cytoplasmic IIAB(Man) subunit. IIAB(Man) has two
      flexibly linked domains, IIA(Man) and IIB(Man), each containing a phosphorylation
      site (His-10 and His-175). Phosphoryl groups are transferred from the phosphoryl
      carrier protein phospho-HPr to His-10, hence to His-175 and finally to the 6' OH
      of the transported hexose. Phosphate-binding sites and phosphate-catalytic sites
      frequently contain arginines, which by their guanidino group can stabilize
      phosphate through hydrogen bonding and electrostatic interactions. IIB(Man)
      contains five arginines which are invariant in the homologous IIB subunits of
      Escherichia coli, Klebsiella pneumoniae and Bacillus subtilis. The IIA domains
      have no conserved arginines. The five arginines were replaced by Lys or Gln one
      at a time, and the mutants were analyzed for transport and phosphorylation
      activity. All five IIB mutants can still be phosphorylated at His-175 by the IIA
      domain. R172Q is completely inactive with respect to glucose phosphotransferase
      (phosphoryltransfer from His-175 to the 6' OH of Glc) and hexose transport
      activity. R168Q has no hexose transport and strongly reduced phosphotransferase
      activity. R204K has no transport but almost normal phosphotransferase activity.
      R304Q has only slightly reduced transport activity. R190K behaves like wild-type
      IIAB(Man). Arg-168, Arg-172, and Arg-304 are part of the hydrogen bonding network
      on the surface of IIB, which contains the active site His-175 and the interface
      with the IIA domain (Schauder, S., Nunn, R.S., Lanz, R., Erni, B. and Schirmer,
      T. (1998) J. Mol. Biol. 276, 591-602) (Protein Data Bank accession code 1BLE).
      Arg-204 is at the putative interface between IIB(Man) and the IIC(Man)-IID(Man)
      complex.

PMID- 9575173
TI  - The glucose transporter of the Escherichia coli phosphotransferase system. Mutant
      analysis of the invariant arginines, histidines, and domain linker.
AB  - The glucose transporter of the bacterial phosphotransferase system (PTS) consists
      of a hydrophilic (IIAGlc) and a transmembrane subunit (IICBGlc). IICBGlc has two
      domains (C and B), which are linked by a highly invariant sequence. Transport of
      glucose by IIC and phosphorylation by IIB are tightly coupled processes. Three
      motifs that are strongly conserved in 12 homologous PTS transporters, namely two
      invariant arginines (Arg-424 and Arg-426) adjacent to the phosphorylation site
      (Cys-421), the invariant interdomain sequence KTPGRED, and two conserved
      histidines (His-211 and His-212) in the IIC domain were mutated and the mutant
      proteins characterized in vivo and in vitro for transport and phosphorylation
      activity. Replacement of the strongly beta-turn favoring residues Thr and Gly of
      the linker by alpha-helix favoring Ala results in strong reduction of activity,
      whereas the substitutions of the other residues have only minor effects. The
      R424K and R426K mutants can be phosphorylated by IIAGlc but can no longer donate
      the phosphoryl group to glucose. The H211Q and H212Q mutants continue to
      phosphorylate glucose at a reduced rate but H212Q can no longer transport
      glucose. Mixtures of purified R424K/H212Q and R426K/H212Q have 10% of wild-type
      phosphorylation activity and when coexpressed in Escherichia coli support glucose
      transport.

PMID- 9575174
TI  - Interactions of type IV collagen and its domains with human mesangial cells.
AB  - Type IV collagen (COL-IV) interacts with a variety of cell types. We present
      evidence that human mesangial cells (HMC) bind directly to COL-IV, its major
      triple helical domain, and the main non-collagenous, NC1 domain. A synthetic
      peptide, HEP-III, and its triple helical counterpart (THP-III), previously
      reported to be a heparin-binding domain, also promoted approximately 15% adhesion
      of HMC. HMC bound to solid-phase-immobilized, intact COL-IV (approximately 75%),
      isolated NC1 domain (approximately 15%), and a pepsin-derived triple helical
      fragment,which lacks Hep-III (approximately 65%). We further examined inhibition
      of HMC adhesion to COL-IV and its domains by using anti-integrin antibodies.
      Blocking monoclonal antibodies against the alpha2 integrin resulted in 70%
      inhibition of adhesion to COL-IV and 80% inhibition to HEP-III. Moderate
      inhibition was observed on the NC1 and triple helical fragments. Anti-alpha1
      antibodies inhibited the binding of HMC to COL-IV, the NC1, and triple helical
      domains, but not to peptide HEP-III. Anti-beta1 antibodies inhibited almost
      completely (>95%) the adhesion to COL-IV, the NC1, and triple helical fragments;
      inhibition on HEP-III was approximately 30%. Affinity chromatography studies with
      solid-phase HEP-III and mesangial cell lysate also demonstrated the presence of
      integrin alpha2 beta1 along with alpha3 beta1. We conclude that alpha2 beta1 and
      alpha1 beta1 integrins mediate HMC adhesion to COL-IV. Peptide HEP-III is a
      major, specific site for alpha2 integrin-mediated binding of mesangial cells to
      COL-IV. Both the alpha1 beta1 and alpha2 beta1 integrins interact with the NC1
      and triple helical fragments of COL-IV. Therefore, we demonstrate that several
      sites for integrin-mediated interactions exist on several collagenous and non
      collagenous domains of COL-IV.

PMID- 9575175
TI  - Serine/threonine protein phosphatase type 5 acts upstream of p53 to regulate the
      induction of p21(WAF1/Cip1) and mediate growth arrest.
AB  - Understanding how alterations in growth control pathways are translated into
      changes in the cell cycle regulatory machinery is a major challenge for
      understanding the development of human cancers. The ability of both tumor
      suppressor proteins, p53 and BRCA1, to induce the expression of p21(WAF1/Cip1) in
      combination with the inhibitory activity of p21(WAF1/Cip1) against cyclin
      dependent kinases suggests that the regulation of p21(WAF1/Cip1) expression is an
      important aspect of mammalian cell cycle growth control. To elucidate the role of
      serine/threonine protein phosphatase type 5 (PP5) in processes regulating cell
      cycle progression, we developed antisense oligodeoxynucleotides targeted against
      PP5 (e.g. ISIS 15534) that specifically inhibit PP5 gene expression. Employing
      ISIS 15534, we demonstrate that the specific inhibition of PP5 gene expression
      has a marked antiproliferative effect on cells, characterized by induction of
      p21(WAF1/Cip1) and the subsequent arrest of cell growth. Investigations into the
      mechanisms leading to growth arrest reveal that, in the absence of PP5, the
      expression of p21(WAF1/Cip1) is induced in p53-competent A549 cells but not in
      p53 protein-deficient T-24 cells. Employing a stable cell line derived from p53
      deficient human fibroblast that contains tetracycline-regulated transactivator
      and operator plasmids to control the expression of wild-type p53 (TR9-7 cells),
      we then show that the induction of p21(WAF1/Cip1), which occurs in response to
      the inhibition of PP5 expression, requires the p53 protein. Additional studies
      indicate that PP5 acts upstream of p53, influencing both the phosphorylation
      state and the ability of p53 to bind DNA, without causing an increase in p53 gene
      transcription. Together these studies suggest that PP5 is a regulatory component
      of a signaling pathway that affords replicating cells G1 checkpoint growth
      control and that it is the regulation of PP5 that, in turn, controls p53-mediated
      expression of p21(WAF1/Cip1) and growth arrest in this pathway. In addition,
      since the inhibition of PP5 gene expression has marked antiproliferative activity
      and the overexpression of p21(WAF1/Cip1) blocks the growth of tumor cells, these
      studies suggest that compounds that inhibit of PP5 gene expression may be useful
      in the treatment of human cancers.

PMID- 9575176
TI  - Expression and characterization of the catalytic core of tryptophan hydroxylase.
AB  - Wild type rabbit tryptophan hydroxylase (TRH) and two truncated mutant proteins
      have been expressed in Escherichia coli. The wild type protein was only expressed
      at low levels, whereas the mutant protein lacking the 101 amino-terminal
      regulatory domain was predominantly found in inclusion bodies. The protein that
      also lacked the carboxyl-terminal 28 amino acids, TRH102-416, was expressed as
      30% of total cell protein. Analytical ultracentrifugation showed that TRH102-416
      was predominantly a monomer in solution. The enzyme exhibited an absolute
      requirement for iron (ferrous or ferric) for activity and did not turn over in
      the presence of cobalt or copper. With either phenylalanine or tryptophan as
      substrate, stoichiometric formation of the 4a-hydroxypterin was found. Steady
      state kinetic parameters were determined with both of these amino acids using
      both tetrahydrobiopterin and 6-methyltetrahydropterin.

PMID- 9575177
TI  - Inositol 1,3,4,5-tetrakisphosphate binding activities of neuronal and non
      neuronal synaptotagmins. Identification of conserved amino acid substitutions
      that abolish inositol 1,3,4,5-tetrakisphosphate binding to synaptotagmins III, V,
      and X.
AB  - Synaptotagmins I and II are essential for Ca2+-regulated exocytosis of synaptic
      vesicles from neurons, probably serving as Ca2+ sensors. This Ca2+-sensing
      function is thought to be disrupted by binding of an inositol 1,3,4,5
      tetrakisphosphate (IP4) to the C2B domain of synaptotagmin I or II (Fukuda, M.,
      Moreira, J. E., Lewis, F. M. T., Sugimori, M., Niinobe, M., Mikoshiba, K., and
      Llinas, R. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 10708-10712). Recently,
      several synaptotagmin isoforms, expressed outside the nervous system, have been
      identified in rats and proposed to be involved in constitutive vesicle traffic.
      To test whether the inositol high polyphosphates also regulate constitutive
      vesicle traffic by binding to the non-neuronal synaptotagmins, we examined the
      IP4 binding properties of the recombinant C2 domains of both neuronal (III, V, X,
      and XI) and non-neuronal (VI-VIII and IX) synaptotagmins. The C2B domains of
      synaptotagmins VII-IX and XI had strong IP4 binding activity, but the C2B domain
      of synaptotagmin VI showed very weak IP4 binding activity. In contrast, there was
      no significant IP4 binding activity of the C2B domains of synaptotagmins III, V,
      and X or any of the C2A domains. A phylogenetic tree of the C2 domains of 11
      isoforms revealed that synaptotagmins III, V, VI, and X (IP4-insensitive or very
      weak IP4-binding isoforms) belong to the same branch. Based on the sequence
      comparison between the IP4-sensitive and -insensitive isoforms, we performed site
      directed mutagenesis of synaptotagmin III and identified several amino acid
      substitutions that abolish IP4 binding activity. Our data suggest that the
      inositol high polyphosphates might also regulate constitutive vesicle traffic via
      binding to the IP4-sensitive non-neuronal synaptotagmins.

PMID- 9575178
TI  - DNA strand invasion promoted by Escherichia coli RecT protein.
AB  - The RecT protein of Escherichia coli is a DNA-pairing protein required for the
      RecA-independent recombination events promoted by the RecE pathway. The RecT
      protein was found to bind to both single-stranded DNA (ssDNA) and double-stranded
      DNA (dsDNA) in the absence of Mg2+. In the presence of Mg2+, RecT binding to
      dsDNA was inhibited drastically, whereas binding to ssDNA was inhibited only to a
      small extent. RecT promoted the transfer of a single-stranded oligonucleotide
      into a supercoiled homologous duplex to form a D (displacement)-loop. D-loop
      formation occurred in the absence of Mg2+ and at 1 mM Mg2+ but was inhibited by
      increasing concentrations of Mg2+ and did not require a high energy cofactor.
      Strand transfer was mediated by a RecT-ssDNA nucleoprotein complex reacting with
      a naked duplex DNA and was prevented by the formation of RecT-dsDNA nucleoprotein
      complexes. Finally, RecT mediated the formation of joint molecules between a
      supercoiled DNA and a linear dsDNA substrate with homologous 3'-single-stranded
      tails. Together these results indicate that RecT is not a helix-destabilizing
      protein promoting a reannealing reaction but rather is a novel type of pairing
      protein capable of promoting recombination by a DNA strand invasion mechanism.
      These results are consistent with the observation that RecE (exonuclease VIII)
      and RecT can promote RecA-independent double-strand break repair in E. coli.

PMID- 9575179
TI  - Suramin is an active site-directed, reversible, and tight-binding inhibitor of
      protein-tyrosine phosphatases.
AB  - The effect of suramin, a well known antitrypanosomal drug and a novel
      experimental agent for the treatment of several cancers, on protein-tyrosine
      phosphatases (PTPases) has been examined. Suramin is a reversible and competitive
      PTPase inhibitor with Kis values in the low microM range, whereas the Kis for the
      dual specificity phosphatase VHR is at least 10-fold higher. Although suramin can
      also inhibit the activity of the potato acid phosphatase at a slightly higher
      concentration, it is 2-3 orders of magnitude less effective against the protein
      Ser/Thr phosphatase 1alpha and the bovine intestinal alkaline phosphatase.
      Suramin binds to the active site of PTPases with a binding stoichiometry of 1:1.
      Furthermore, when suramin is bound to the active site of PTPases, its
      fluorescence is enhanced approximately by 10-fold. This property has allowed the
      determination of the binding affinity of suramin for PTPases and several
      catalytically impaired mutant PTPases by fluorescence titration techniques. Thus,
      the active site Cys to Ser mutants bind suramin with similar affinity as the wild
      type, while the active site Arg to Ala mutant exhibits a 20-fold reduced affinity
      toward suramin. Interestingly, the general acid deficient Asp to Ala mutant
      PTPases display an enhanced affinity toward suramin, which is in accord with
      their use as improved "substrate-trapping" agents. That suramin is a high
      affinity PTPase inhibitor is consistent with the observation that suramin
      treatment of cancer cell lines leads to an increase in tyrosine phosphorylation
      of several cellular proteins. Given the pleiotropic effects of suramin on many
      enzyme systems and growth factor-receptor interactions, the exact in vivo actions
      of suramin require further detailed structure-activity investigation of suramin
      and its structural analogs.

PMID- 9575180
TI  - Binding of retinoic acid receptor heterodimers to DNA. A role for histones NH2
      termini.
AB  - The retinoic acid signaling pathway is controlled essentially through two types
      of nuclear receptors, RARs and RXRs. Ligand dependent activation or repression of
      retinoid-regulated genes is dependent on the binding of retinoic acid receptor
      (RAR)/9-cis-retinoic acid receptor (RXR) heterodimers to retinoic acid response
      element (RARE). Although unliganded RXR/RAR heterodimers bind constitutively to
      DNA in vitro, a clear in vivo ligand-dependent occupancy of the RARE present in
      the RARbeta2 gene promoter has been reported (Dey, A., Minucci, S., and Ozato, K.
      (1994) Mol. Cell. Biol. 14, 8191-8201). Nucleosomes are viewed as general
      repressors of the transcriptional machinery, in part by preventing the access of
      transcription factors to DNA. The ability of hRXRalpha/hRARalpha heterodimers to
      bind to a nucleosomal template in vitro has therefore been examined. The assembly
      of a fragment from the RARbeta2 gene promoter, which contains a canonical DR5
      RARE, into a nucleosome core prevented hRXRalpha/hRARalpha binding to this DNA,
      in conditions where a strong interaction is observed with a linear DNA template.
      However, histone tails removal by limited proteolysis and histone
      hyperacetylation yielded nucleosomal RAREs able to bind to hRXRalpha/hRARalpha
      heterodimers. These data establish therefore the role of histones NH2 termini as
      a major impediment to retinoid receptors access to DNA, and identify histone
      hyperacetylation as a potential physiological regulator of retinoid-induced
      transcription.

PMID- 9575181
TI  - RICK, a novel protein kinase containing a caspase recruitment domain, interacts
      with CLARP and regulates CD95-mediated apoptosis.
AB  - Signaling through the CD95/Fas/APO-1 death receptor plays a critical role in the
      homeostasis of the immune system. RICK, a novel protein kinase that regulates
      CD95-mediated apoptosis was identified and characterized. RICK is composed of an
      N-terminal serine-threonine kinase catalytic domain and a C-terminal region
      containing a caspase-recruitment domain. RICK physically interacts with CLARP, a
      caspase-like molecule known to bind to Fas-associated protein with death domain
      (FADD) and caspase-8. Expression of RICK promoted the activation of caspase-8 and
      potentiated apoptosis induced by Fas ligand, FADD, CLARP, and caspase-8. Deletion
      mutant analysis revealed that both the kinase domain and caspase-recruitment
      domain were required for RICK to promote apoptosis. Significantly, expression of
      a RICK mutant in which the lysine of the putative ATP-binding site at position 38
      was replaced by a methionine functioned as an inhibitor of CD95-mediated
      apoptosis. Thus, RICK represents a novel kinase that may regulate apoptosis
      induced by the CD95/Fas receptor pathway.

PMID- 9575182
TI  - Physical and functional association between thymic shared antigen-1/stem cell
      antigen-2 and the T cell receptor complex.
AB  - Thymic shared antigen-1 (TSA-1)/stem cell Ag-2 (Sca-2) is a
      glycosylphosphatidylinositol (GPI)-anchored antigen expressed on lymphocytes. We
      have previously demonstrated that a signal via TSA-1/Sca-2 inhibits T cell
      receptor (TCR)-mediated T cell activation and apoptosis. To elucidate a molecular
      mechanism for TSA-1-mediated modulation of the TCR-signaling pathway, we examined
      whether TSA-1 is physically coupled to the TCR in the present study. TSA-1 was
      clearly associated with CD3zeta chains in T cell hybridomas, activated T cells,
      and COS-7 cells transfected with TSA-1 and CD3zeta cDNA. The physical association
      was confirmed on the surface of T cells in immunoprecipitation and confocal
      microscopy. The analysis using stable and transient transfectants expressing a
      transmembrane form of TSA-1 revealed that the association of CD3zeta did not
      require the GPI anchor of TSA-1. Finally, tyrosine phosphorylation of CD3zeta
      chains was induced after stimulation with anti-TSA-1, suggesting that a
      functional association between these two molecules also exists. These results
      imply that the physical association to CD3zeta underlies a regulatory role of TSA
      1/Sca-2 in the TCR-signaling pathway.

PMID- 9575183
TI  - Functional analysis of diastrophic dysplasia sulfate transporter. Its involvement
      in growth regulation of chondrocytes mediated by sulfated proteoglycans.
AB  - Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene
      constitute a family of recessively inherited osteochondrodysplasias including
      achondrogenesis type 1B, atelosteogenesis type II, and diastrophic dysplasia.
      However, the functional properties of the gene product have yet to be elucidated.
      We cloned rat DTDST cDNA from rat UMR-106 osteoblastic cells. Northern blot
      analysis suggested that cartilage and intestine were the major expression sites
      for DTDST mRNA. Analysis of the genomic sequence revealed that the rat DTDST gene
      was composed of at least five exons. Two distinct transcripts were expressed in
      chondrocytes due to alternative utilization of the third exon, corresponding to
      an internal portion of the 5'-untranslated region of the cDNA. Injection of rat
      and human DTDST cRNA into Xenopus laevis oocytes induced Na+-independent sulfate
      transport. Transport activity of the expressed DTDST was markedly inhibited by
      extracellular chloride and bicarbonate. In contrast, canalicular Na+-independent
      sulfate transporter Sat-1 required the presence of extracellular chloride in the
      cRNA-injected oocytes. The activity profile of sulfate transport in growth plate
      chondrocytes was studied in the extracellular presence of various anions and
      found substantially identical to DTDST expressed in oocytes. Thus, sulfate
      transport of chondrocytes is dominantly dependent on the DTDST system. Finally,
      we demonstrate that undersulfation of proteoglycans by the chlorate treatment of
      chondrocytes significantly impaired growth response of the cells to fibroblast
      growth factor, suggesting a role for DTDST in endochondral bone formation.

PMID- 9575184
TI  - The G protein-coupled receptor kinase 2 is a microtubule-associated protein
      kinase that phosphorylates tubulin.
AB  - The G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase that
      phosphorylates and desensitizes agonist-occupied G protein-coupled receptors
      (GPCRs). Here we demonstrate that GRK2 is a microtubule-associated protein and
      identify tubulin as a novel GRK2 substrate. GRK2 is associated with microtubules
      purified from bovine brain, forms a complex with tubulin in cell extracts, and
      colocalizes with tubulin in living cells. Furthermore, an endogenous tubulin
      kinase activity that copurifies with microtubules has properties similar to GRK2
      and is inhibited by anti-GRK2 monoclonal antibodies. Indeed, GRK2 phosphorylates
      tubulin in vitro with kinetic parameters very similar to those for
      phosphorylation of the agonist-occupied beta2-adrenergic receptor, suggesting a
      functionally relevant role for this phosphorylation event. In a cellular
      environment, agonist occupancy of GPCRs, which leads to recruitment of GRK2 to
      the plasma membrane and its subsequent activation, promotes GRK2-tubulin complex
      formation and tubulin phosphorylation. These findings suggest a novel role for
      GRK2 as a GPCR signal transducer mediating the effects of GPCR activation on the
      cytoskeleton.

PMID- 9575185
TI  - Molecular recognition of cyclic urea HIV-1 protease inhibitors.
AB  - As long as the threat of human immunodeficiency virus (HIV) protease drug
      resistance still exists, there will be a need for more potent antiretroviral
      agents. We have therefore determined the crystal structures of HIV-1 protease in
      complex with six cyclic urea inhibitors: XK216, XK263, DMP323, DMP450, XV638, and
      SD146, in an attempt to identify 1) the key interactions responsible for their
      high potency and 2) new interactions that might improve their therapeutic
      benefit. The structures reveal that the preorganized, C2 symmetric scaffolds of
      the inhibitors are anchored in the active site of the protease by six hydrogen
      bonds and that their P1 and P2 substituents participate in extensive van der
      Waals interactions and hydrogen bonds. Because all of our inhibitors possess
      benzyl groups at P1 and P1', their relative binding affinities are modulated by
      the extent of their P2 interactions, e.g. XK216, the least potent inhibitor (Ki
      (inhibition constant) = 4.70 nM), possesses the smallest P2 and the lowest number
      of P2-S2 interactions; whereas SD146, the most potent inhibitor (Ki = 0.02 nM),
      contains a benzimidazolylbenzamide at P2 and participates in fourteen hydrogen
      bonds and approximately 200 van der Waals interactions. This analysis identifies
      the strongest interactions between the protease and the inhibitors, suggests ways
      to improve potency by building into the S2 subsite, and reveals how
      conformational changes and unique features of the viral protease increase the
      binding affinity of HIV protease inhibitors.

PMID- 9575186
TI  - Evidence from transgenic mice that interferon-beta may be involved in the onset
      of diabetes mellitus.
AB  - A number of cytokines have been shown to alter the function of pancreatic beta
      cells and thus might be involved in the development of type 1 diabetes.
      Interferon-beta (IFN-beta) expression is induced in epithelial cells by several
      viruses, and it has been detected in islets of type 1 diabetic patients. Here we
      show that treatment of isolated mouse islets with this cytokine was able to alter
      insulin secretion in vitro. To study whether IFN-beta alters beta-cell function
      in vivo and leads to diabetes, we have developed transgenic mice (C57BL6/SJL)
      expressing IFN-beta in beta-cells. These mice showed functional alterations in
      islets and impaired glucose-stimulated insulin secretion. Transgenic animals
      presented mild hyperglycemia, hypoinsulinemia, hypertriglyceridemia, and altered
      glucose tolerance test, all features of a prediabetic state. However, they
      developed overt diabetes, with lymphocytic infiltration of the islets, when
      treated with low doses of streptozotocin, which did not induce diabetes in
      control mice. In addition, about 9% of the transgenic mice obtained from the N3
      back-cross to outbred albino CD-1 mice spontaneously developed severe
      hyperglycemia and hypoinsulinemia and showed mononuclear infiltration of the
      islets. These results suggest that IFN-beta may be involved in the onset of type
      1 diabetes when combined with either an additional factor or a susceptible
      genetic background.

PMID- 9575187
TI  - Secreted beta-amyloid precursor protein counteracts the proapoptotic action of
      mutant presenilin-1 by activation of NF-kappaB and stabilization of calcium
      homeostasis.
AB  - Mutations in the presenilin-1 (PS-1) gene account for approximately 50% of the
      cases of autosomal dominant, early onset, inherited forms of Alzheimer's disease
      (AD). PS-1 is an integral membrane protein expressed in neurons and is localized
      primarily in the endoplasmic reticulum (ER). PS-1 mutations may promote neuronal
      degeneration by altering the processing of the beta-amyloid precursor protein
      (APP) and/or by engaging apoptotic pathways. Alternative processing of APP in AD
      may increase production of neurotoxic amyloid beta-peptide (Abeta) and reduce
      production of the neuroprotective alpha-secretase-derived form of APP
      (sAPPalpha). In differentiated PC12 cells expressing an AD-linked PS-1 mutation
      (L286V), sAPPalpha activated the transcription factor NF-kappaB and prevented
      apoptosis induced by Abeta. Treatment of cells with kappaB decoy DNA blocked the
      antiapoptotic action of sAPPalpha, demonstrating the requirement for NF-kappaB
      activation in the cytoprotective action of sAPPalpha. Cells expressing mutant PS
      1 exhibited an aberrant pattern of NF-kappaB activity following exposure to
      Abeta, which was characterized by enhanced early activation of NF-kappaB followed
      by a prolonged depression of activity. Blockade of NF-kappaB activity in cells
      expressing mutant PS-1 by kappaB decoy DNA was associated with enhanced Abeta
      induced increases of [Ca2+]i and mitochondrial dysfunction. Treatment of cells
      with sAPPalpha stabilized [Ca2+]i and mitochondrial function and suppressed
      oxidative stress by a mechanism involving activation of NF-kappaB. Blockade of ER
      calcium release prevented (and stimulation of ER calcium release by thapsigargin
      induced) apoptosis in cells expressing mutant PS-1, suggesting a pivotal role for
      ER calcium release in the proapoptotic action of mutant PS-1. Finally, a role for
      NF-kappaB in preventing apoptosis induced by ER calcium release was demonstrated
      by data showing that sAPPalpha prevents thapsigargin-induced apoptosis, an effect
      blocked by kappaB decoy DNA. We conclude that sAPPalpha stabilizes cellular
      calcium homeostasis and protects neural cells against the proapoptotic action of
      mutant PS-1 by a mechanism involving activation of NF-kappaB. The data further
      suggest that PS-1 mutations result in aberrant NF-kappaB regulation that may
      render neurons vulnerable to apoptosis.

PMID- 9575188
TI  - Induced activation of the Toxoplasma gondii nucleoside triphosphate hydrolase
      leads to depletion of host cell ATP levels and rapid exit of intracellular
      parasites from infected cells.
AB  - The nucleoside triphosphate hydrolase of Toxoplasma gondii is a potent apyrase.
      The protein is synthesized in large amounts and transported through the secretory
      pathway of the parasite and into the vacuolar space in an oxidized and thereby
      enzymatically inactive form. Complete activation of the purified enzyme is known
      to require dithiols (e.g. DTT); subcellular fractionation demonstrates that
      little if any (<5%) of the enzyme in the vacuolar space is active in the absence
      of DTT. Both native and epitope-tagged nucleoside triphosphate hydrolase (NTPase)
      were partially activated during immunoprecipitation, precluding precise
      assessment of enzyme activity in the vacuolar space but suggesting that protein
      protein interactions may trigger activation. When infected cells were treated
      with DTT, the NTPase was activated in a dose-response fashion, as assessed by
      migration on SDS-polyacrylamide gel electrophoresis and by an increase in
      enzymatic activity. After activation, enzyme activity decreased with time in the
      presence of DTT; this inactivation was slowed by the presence of excess ATP. A
      rapid fall in host cell ATP was accompanied by an abrupt exit of parasites from
      cells. These results demonstrate that the oxidation/reduction status of the
      NTPase, the only parasite dense granule protein that contains disulfide bonds, is
      tightly controlled within the vacuolar space and may influence parasite exit from
      cells.

PMID- 9575189
TI  - Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle
      sarcoplasmic reticulum Ca2+-ATPase.
AB  - The 31-amino acid proteolipid, sarcolipin (SLN), is associated with the fast
      twitch skeletal muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA1). Constructs of
      human and rabbit SLN and of rabbit SLN with the FLAG epitope at its N terminus
      (NF-SLN) or its C terminus (SLN-FC) were coexpressed with SERCA1 in HEK-293 T
      cells. Immunohistochemistry was used to demonstrate colocalization of NF-SLN and
      SERCA1 in the endoplasmic reticulum membrane and to demonstrate the cytosolic
      orientation of the N terminus of SLN. Coexpression of native rabbit SLN or NF-SLN
      with SERCA1 decreased the apparent affinity of SERCA1 for Ca2+ but stimulated
      maximal Ca2+ uptake rates (Vmax). The N terminus of SLN is not well conserved
      among species, and the addition of an N-terminal FLAG epitope did not alter SLN
      function. Anti-FLAG antibody reversed both the inhibition of Ca2+ uptake by NF
      SLN at low Ca2+ concentrations and the stimulatory effect of NF-SLN on Vmax.
      Addition of the FLAG epitope to the highly conserved C terminus decreased the
      apparent affinity of SERCA1 for Ca2+ relative to native SLN and decreased Vmax
      significantly. Mutations in the C-terminal domain showed that this sequence is
      critical for SLN function. Mutational analysis of the transmembrane helix,
      together with the additive regulatory effects of coexpression of both SLN and
      phospholamban (PLN) with SERCA1, provided evidence for different mechanisms of
      interaction of SLN and PLN with SERCA molecules. Ca2+ uptake rates in
      sarcoplasmic reticulum vesicles, isolated from rabbit fast-twitch muscle
      (tibialis anterior) subjected to chronic low frequency stimulation, were reduced
      by approximately 40% in 3- and 4-day stimulated muscle, with a marginal increase
      in apparent affinity of SERCA1 for Ca2+. SERCA1 mRNA and protein levels were
      unaltered after stimulation. In contrast, SLN mRNA was decreased by 15%, and SLN
      protein was reduced by 40%. Reduced SLN expression could explain the decrease in
      SERCA1 activity observed in these muscles and might represent an early functional
      adaptation to chronic low frequency stimulation.

PMID- 9575190
TI  - Potato carboxypeptidase inhibitor, a T-knot protein, is an epidermal growth
      factor antagonist that inhibits tumor cell growth.
AB  - Epidermal growth factor (EGF) and its receptor (EGFR) are involved in many
      aspects of the development of carcinomas, including tumor cell growth,
      vascularization, invasiveness, and metastasis. Because EGFR has been found to be
      overexpressed in many tumors of epithelial origin, it is a potential target for
      antitumor therapy. Here we report that potato carboxypeptidase inhibitor (PCI), a
      39-amino acid protease inhibitor with three disulfide bridges, is an antagonist
      of human EGF. It competed with EGF for binding to EGFR and inhibited EGFR
      activation and cell proliferation induced by this growth factor. PCI suppressed
      the growth of several human pancreatic adenocarcinoma cell lines, both in vitro
      and in nude mice. PCI has a special disulfide scaffold called a T-knot that is
      also present in several growth factors including EGF and transforming growth
      factor alpha. PCI shows structural similarities with these factors, a fact that
      can explain the antagonistic effect of the former. This is the first reported
      example of an antagonistic analogue of human EGF.

PMID- 9575191
TI  - T lymphocyte activation signals for interleukin-2 production involve activation
      of MKK6-p38 and MKK7-SAPK/JNK signaling pathways sensitive to cyclosporin A.
AB  - p38/CSBP, a subgroup member of mitogen-activated protein kinase (MAPK)
      superfamily molecules, is known to be activated by proinflammatory cytokines and
      environmental stresses. We report here that p38 is specifically activated by
      signals that lead to interleukin-2 (IL-2) production in T lymphocytes. A p38
      activator MKK6 was also markedly activated by the same stimulation. Pretreatment
      of cells with SB203580, a specific inhibitor of p38, as well as expression of a
      dominant-negative mutant of MKK6, suppressed the transcriptional activation of
      the IL-2 promoter. We also demonstrated that MKK7, a recently described MAPK
      kinase family member, plays a major role in the activation of stress-activated
      protein kinase (SAPK)/c-Jun NH2-terminal kinase (JNK) in T lymphocytes. Moreover,
      a dominant-negative mutant of MKK7 abrogated the transcriptional activation of
      the distal nuclear factor of activated T cells response element in the IL-2
      promoter. Cyclosporin A, a potent immunosuppressant, inhibited activation of both
      p38 and SAPK/JNK pathways but not the MAPK/extracellular signal-regulated kinase
      (ERK) pathway. Our results indicate that both MKK6 to p38 and MKK7 to SAPK/JNK
      signaling pathways are activated in a cyclosporin A-sensitive manner and
      contribute to IL-2 gene expression in T lymphocytes.

PMID- 9575192
TI  - DNA duplexes containing 3'-deoxynucleotides as substrates for DNA topoisomerase I
      cleavage and ligation.
AB  - The DNA cleavage-ligation reaction of DNA topoisomerase I was investigated
      employing synthetic DNA substrates containing 3'-deoxyadenosine or 3'
      deoxythymidine at specific sites and acceptor oligonucleotides of different
      lengths. The modified nucleotides were substituted systematically within the
      putative enzyme-binding domain and also next to the high efficiency cleavage site
      to determine the effect of single base changes on enzyme function. Depending on
      the site of substitution, the facility of the cleavage and ligation reactions
      were altered. The bases at positions -1 and -2 on the noncleaved strand were
      found to be important for determining the site of cleavage. Inclusion of 3'
      deoxythymidine in the scissile strand at position -1 permitted the demonstration
      that topoisomerase I can cleave and form a 2' --> 5'-phosphodiester linkage.
      Partial duplexes doubly modified at positions -4 or -6 in the noncleaved strand
      and at positions +1 or -1 within scissile strand were not good substrates for
      topoisomerase I, showing that cleavage can depend importantly on binding
      interactions based on structural alterations at spatially separated sites.
      Substitution of a 3'-deoxynucleotide on the scissile strand at position -6
      enhanced formation of the ligation product resulting from cleavage at site 1 and
      suppressed cleavage at site 2.

PMID- 9575193
TI  - Membrane topology of NHE3. Epitopes within the carboxyl-terminal hydrophilic
      domain are exoplasmic.
AB  - Experimental data indicate that the relatively hydrophilic carboxyl-terminal
      domains of Na+-H+ exchangers mediate the regulation of transporter activity
      through interactions with cytoskeletal effectors. It has therefore been assumed
      that this entire domain lies on the cytoplasmic surface of the plasma membrane.
      The purpose of the present study was to determine the membrane orientation of the
      COOH-terminal 131 amino acids of Na+-H+ exchanger isoform NHE3 by use of three
      monoclonal antibodies that recognize at least two distinct epitopes within this
      region. Enzyme-linked immunosorbent assay studies demonstrated binding of these
      monoclonal antibodies (mAbs) to intact right-side-out renal brush border membrane
      vesicles in the absence of detergent. Moreover, when coupled to an affinity
      matrix to isolate membrane vesicles, the anti-NHE3 mAbs bound structures that
      were morphologically identical to intact microvilli. To confirm the identity of
      the exoplasmic antigen bound by the antibodies, immunoprecipitation studies were
      performed. Intact right-side-out brush border membrane vesicles were incubated
      with the mAbs in the absence of detergent. The membranes were pelleted,
      supernatant with unbound antibody was removed, the pellet was solubilized, and
      then immunoprecipitation with secondary antibody was performed. Immunoblot
      analysis indicated that NHE3 was precipitated after binding of the mAbs to intact
      membranes. Finally, the localization of the mAb epitopes was determined using
      high resolution immunocytochemistry. Ultrathin cryosections of rat kidney were
      labeled with the mAbs and bound antibody detected with the colloidal gold
      technique. Labeling was restricted to the exoplasmic surface of microvilli of the
      proximal tubule. Taken together, these findings indicate that epitopes within the
      carboxyl terminus of the Na+-H+ exchanger isoform NHE3 are exposed to the outside
      of the plasma membrane.

PMID- 9575194
TI  - Electromagnetic field-induced stimulation of Bruton's tyrosine kinase.
AB  - Here we present evidence that exposure of DT40 lymphoma B-cells to low energy
      electromagnetic fields (EMF) results in activation of phospholipase C-gamma 2
      (PLC-gamma2), leading to increased inositol phospholipid turnover. PLC-gamma2
      activation in EMF-stimulated cells is mediated by stimulation of the Bruton's
      tyrosine kinase (BTK), a member of the Src-related TEC family of protein tyrosine
      kinases, which acts downstream of LYN kinase and upstream of PLC-gamma2. B-cells
      rendered BTK-deficient by targeted disruption of the btk gene did not show
      enhanced PLC-gamma2 activation in response to EMF exposure. Introduction of the
      wild-type (but not a kinase domain mutant) human btk gene into BTK-deficient B
      cells restored their EMF responsiveness. Thus, BTK exerts a pivotal and mandatory
      function in initiation of EMF-induced signaling cascades in B-cells.

PMID- 9575195
TI  - A mitogen-activated protein kinase pathway is required for mu-opioid receptor
      desensitization.
AB  - The mu-opioid receptor mediates not only the beneficial painkilling effects of
      opiates like morphine but also the detrimental effects of chronic exposure such
      as tolerance and dependence. Different studies have linked tolerance to opioid
      receptor desensitization. Agonist activation of the mu-opioid receptor stimulates
      a mitogen-activated protein kinase (MAPK) activity, but the functional
      significance of this pathway remains unclear. We have focused on the MAPK
      signaling cascade to study mu-opioid receptor desensitization. We report that
      inhibition of the MAPK pathway blocks desensitization of mu-opioid receptor
      signaling as well as the loss of receptor density due to internalization. Our
      results suggest that a feedback signal emanating from the MAPK cascade is
      required for mu-opioid receptor desensitization.

PMID- 9575196
TI  - Structural and functional properties of complement-activating protein M161Ag, a
      Mycoplasma fermentans gene product that induces cytokine production by human
      monocytes.
AB  - Human malignant cells are targeted by homologous complement C3b if they express
      M161Ag, a 43-kDa protein with C3-activating property. cDNA of M161Ag cloned from
      human leukemia cell lines predicted M161Ag as a novel secretory protein comprised
      of 428 amino acids including 5 amino acids encoded by TGA codons (Matsumoto M.,
      Takeda, J., Inoue, N., Hara, T., Hatanaka, M., Takahashi, K., Nagasawa, S.,
      Akedo, H., and Seya, T. (1997) Nat. Med. 3, 1266-1270), although the origin of
      this gene was obscure. Here we clarified this point through genomic and
      biochemical analysis: 1) 5'-UT and genomic sequences represented the prokaryote
      promoter and ribosomal binding site; 2) the TGA codons in M161Ag cDNA were
      translated not into selenocysteines but into tryptophans; 3) M161Ag anchored onto
      the membrane secondary to its N-terminal palmitoylation like prokaryote
      lipoproteins; 4) genomic and cDNA clones of M161Ag were highly homologous to
      Mycoplasma fermentans gene encoding P48, a monocytic differentiation/activation
      factor, recently released in the data base, although the resultant proteins were
      different in the amino acid sequences. Additionally, purified soluble M161Ag
      efficiently provoked IL-1beta, tumor necrosis factor alpha, and IL-6 like P48,
      and further IL-10 and IL-12 in human peripheral blood monocytes. Thus, M161Ag
      originates from M. fermentans, and latently infected M. fermentans allows human
      cells to produce M161Ag. The liberated protein serves as a potent modulator of
      innate and cellular immune responses via its complement-activating and cytokine
      producing activities.

PMID- 9575197
TI  - Adenovirus E1B-19K/BCL-2 interacting protein BNIP3 contains a BH3 domain and a
      mitochondrial targeting sequence.
AB  - Adenovirus E1B-19K and BCL-2 anti-apoptosis proteins interact with certain BCL-2
      family pro-apoptotic proteins. A conserved domain, BH3, present in these proteins
      is essential for their pro-apoptotic activity and for heterodimerization with
      anti-apoptosis proteins. Cellular protein BNIP3 (previously NIP3) interacts with
      E1B-19K, BCL-2, BCL-xL, and EBV-BHRF1. BNIP3 contains a motif similar to the BH3
      domain. Deletion of the BH3-like motif in BNIP3 abrogates its ability to
      heterodimerize with E1B-19K and BCL-xL. Substitution of the BH3 domain of BNIP3
      for the corresponding sequences of BAX functionally restores the pro-apoptotic
      and protein heterodimerization activities of BAX. BNIP3 exhibits a delayed cell
      death activity that is partially relieved by deletion of the BH3 domain. BNIP3
      suppresses the anti-apoptosis activity of BCL-xL in a BH3-dependent manner. BNIP3
      contains a C-terminal trans-membrane (TM) domain similar to other BCL-2 family
      proteins and BNIP1 (previously NIP1). The TM domains of BNIP3 and BNIP1 can
      functionally substitute for the TM domain of a BCL-2 family member EBV-BHRF1. The
      BNIP3 TM domain exclusively targets the heterologous green fluorescent protein
      (GFP) to mitochondria. These results suggest that BNIP3 is a member of the BH3
      contaning BCL-2 family of pro-apoptotic proteins and functions in mitochondria.

PMID- 9575198
TI  - A yeast recombinant aquaporin mutant that is not expressed or mistargeted in
      Xenopus oocyte can be functionally analyzed in reconstituted proteoliposomes.
AB  - We have recently identified AQPcic (for aquaporin cicadella), an insect aquaporin
      found in the digestive tract of homopteran insects and involved in the
      elimination of water ingested in excess with the dietary sap (Le Caherec, F.,
      Deschamps, S., Delamarche, C., Pellerin, I., Bonnec, G., Guillam, M. T.,
      Gouranton, J., Thomas, D., and Hubert, J. F. (1996) Eur. J. Biochem. 241, 707
      715). Like many other aquaporins, AQPcic is inhibited by mercury reagents. In
      this study, we have demonstrated that residue Cys82 is essential for mercury
      inhibition. Another mutant version of AQPcic (AQP-C134S), expression of which in
      Xenopus laevis failed to produce an active molecule, was successfully expressed
      in Saccharomyces cerevisiae. Using stopped-flow analysis of reconstituted
      proteoliposomes, we demonstrated that the biological activity and Hg sensitivity
      of yeast-expressed wild type and mutant type AQPcic was readily assessed.
      Therefore, we propose that the yeast system is a valid alternative to Xenopus
      oocytes for studying particular mutants of aquaporin.

PMID- 9575199
TI  - High level expression and dimer characterization of the S100 EF-hand proteins,
      migration inhibitory factor-related proteins 8 and 14.
AB  - The phenotypical and functional heterogeneity of different macrophage
      subpopulations are defined by discrete changes in the expression of two S100
      calcium-binding proteins, migration inhibitory factor-related proteins (MRPs) 8
      and 14. To further our understanding of MRP8 and MRP14 in the developmental
      stages of inflammatory responses, overexpression of the MRPs was obtained through
      a combination of a T7-based expression vector and the Escherichia coli BL21 (DE3)
      cell line. An efficient, two-step chromatographic protocol was then developed for
      rapid, facile purification. Extensive biophysical characterization and chemical
      cross-linking experiments show that MRP8 and MRP14 form oligomers with a strong
      preference to associate as a heterodimer. Heteronuclear NMR experiments indicate
      that a specific well packed dimer is formed only in equimolar mixtures of the two
      proteins. Our results suggest that there is a unique complementarity in the
      interface of the MRP8/MRP14 complex that cannot be fully reproduced in the MRP8
      and MRP14 homodimers.

PMID- 9575201
TI  - Identification of a novel AMP-activated protein kinase beta subunit isoform that
      is highly expressed in skeletal muscle.
AB  - The AMP-activated protein kinase (AMPK) is a member of a growing family of
      related kinases, including the SNF1 complex in yeast, which respond to
      nutritional stress. AMPK is a heterotrimeric complex of a catalytic subunit
      (alpha) and two regulatory subunits (beta and gamma), and proteins related to all
      three subunits have been identified in the SNF1 complex. We have used the two
      hybrid system in order to identify proteins interacting with the catalytic
      subunit (alpha2). Using this approach, we have isolated a novel AMPKbeta isoform,
      which we designate AMPKbeta2. The N-terminal region of beta2 differs
      significantly from that of the previously characterized isoform (beta1),
      suggesting that this region could play a role in isoform-specific AMPK activity.
      Comparison of the C-terminal sequences of beta1 and beta2 with their related
      proteins in yeast identifies two highly conserved regions predicted to be
      involved in binding of the alpha and gamma subunits. The expression of beta1 and
      beta2 was examined in a number of tissues, revealing that the beta1 isoform is
      highly expressed in liver with low expression in skeletal muscle, whereas the
      opposite pattern is observed for the beta2 isoform. These results suggest that
      the beta isoforms have tissue-specific roles, which may involve altered responses
      to upstream signaling and/or downstream targeting of the AMPK complex.

PMID- 9575200
TI  - Subcellular distribution and turnover of presenilins in transfected cells.
AB  - The mechanisms by which mutations in presenilin-1 (PS1) and presenilin-2 (PS2)
      result in the Alzheimer's disease phenotype are unclear. Full-length PS1 and PS2
      are each processed into stable proteolytic fragments after their biosynthesis in
      transfected cells. PS1 and PS2 have been localized by immunocytochemistry to the
      endoplasmic reticulum (ER) and Golgi compartments, but previous studies could not
      differentiate between the full-length presenilin proteins and their fragments. We
      carried out subcellular fractionation of cells stably transfected with PS1 or PS2
      to determine the localization of full-length presenilins and their fragments.
      Full-length PS1 and PS2 were principally distributed in ER fractions, whereas the
      N- and C-terminal fragments were localized predominantly to the Golgi fractions.
      In cells expressing the PS1 mutant lacking exon 9 (DeltaE9), we observed only
      full-length molecules that were present in the ER and Golgi fractions. The
      turnover rate was considerably slower for the DeltaE9 holoprotein, apparently due
      to decreased degradation within the ER. Our results suggest that that full-length
      presenilin proteins are primarily ER resident molecules and undergo
      endoproteolysis within the ER. The fragments are subsequently transported to the
      Golgi compartment, where their turnover rate is much slower than that of the full
      length presenilin in the ER.

PMID- 9575202
TI  - A mutation in the Escherichia coli secY gene that produces distinct effects on
      inner membrane protein insertion and protein export.
AB  - E. coli strains that contain the secY40 mutation are cold-sensitive, but protein
      export defects have not been observed even at the nonpermissive temperature. Here
      we describe experiments designed to explain the conditional phenotype associated
      with this allele. We found that combining the secY40 mutation with defects in the
      signal recognition particle targeting pathway led to synthetic lethality. Since
      the signal recognition particle is required for the insertion of inner membrane
      proteins (IMPs) into the cytoplasmic membrane but not for protein export, this
      observation prompted us to examine the effect of the secY40 mutation on IMP
      biogenesis. The membrane insertion of all IMPs that we tested was impaired at
      both permissive and nonpermissive temperatures in secY40 cells grown in either
      rich or minimal medium. The magnitude of the insertion defects was greatest in
      cells grown at low temperature in rich medium, conditions in which the growth
      defect was most pronounced. Consistent with previous reports, we could not detect
      protein export defects in secY40 cells grown in minimal medium. Upon growth in
      rich medium, only slight protein export defects were observed. Taken together,
      these results suggest that the impairment of IMP insertion causes the cold
      sensitivity of secY40 strains. Furthermore, these results provide the first
      evidence that the protein export and membrane protein insertion functions of the
      translocon are genetically separable.

PMID- 9575203
TI  - Accumulation of a lipid A precursor lacking the 4'-phosphate following
      inactivation of the Escherichia coli lpxK gene.
AB  - The lpxK gene has been proposed to encode the lipid A 4'-kinase in Escherichia
      coli (Garrett, T. A., Kadrmas, J. L., and Raetz, C. R. H. (1997) J. Biol. Chem.
      272, 21855-21864). In cell extracts, the kinase phosphorylates the 4'-position of
      a tetraacyldisaccharide 1-phosphate precursor (DS-1-P) of lipid A, but the enzyme
      has not yet been purified because of instability. lpxK is co-transcribed with an
      essential upstream gene, msbA, with strong homology to mammalian Mdr proteins and
      ABC transporters. msbA may be involved in the transport of newly made lipid A
      from the inner surface of the inner membrane to the outer membrane. Insertion of
      an Omega-chloramphenicol cassette into msbA also halts transcription of lpxK. We
      have now constructed a strain in which only the lpxK gene is inactivated by
      inserting a kanamycin cassette into the chromosomal copy of lpxK. This mutation
      is complemented at 30 degreesC by a hybrid plasmid with a temperature-sensitive
      origin of replication carrying lpxK+. When this strain (designated TG1/pTAG1) is
      grown at 44 degreesC, the plasmid bearing the lpxK+ is lost, and the phenotype of
      an lpxK knock-out mutation is unmasked. The growth of TG1/pTAG1 was inhibited
      after several hours at 44 degreesC, consistent with lpxK being an essential gene.
      Furthermore, 4'-kinase activity in extracts made from these cells was barely
      detectable. In accordance with the proposed biosynthetic pathway for lipid A, DS
      1-P (the 4'-kinase substrate) accumulated in TG1/pTAG1 cells grown at 44
      degreesC. The DS-1-P from TG1/pTAG1 was isolated, and its structure was verified
      by 1H NMR spectroscopy. DS-1-P had not been isolated previously from bacterial
      cells. Its accumulation in TG1/pTAG1 provides additional support for the pathway
      of lipid A biosynthesis in E. coli. Homologs of lpxK are present in the genomes
      of other Gram-negative bacteria.

PMID- 9575205
TI  - Enzymatic and structural similarities between the Escherichia coli ATP-dependent
      proteases, ClpXP and ClpAP.
AB  - Escherichia coli ClpX, a member of the Clp family of ATPases, has ATP-dependent
      chaperone activity and is required for specific ATP-dependent proteolytic
      activities expressed by ClpP. Gel filtration and electron microscopy showed that
      ClpX subunits (Mr 46, 000) associate to form a six-membered ring (Mr
      approximately 280, 000) that is stabilized by binding of ATP or nonhydrolyzable
      analogs of ATP. ClpP, which is composed of two seven-membered rings stacked face
      to-face, interacts with the nucleotide-stabilized hexamer of ClpX to form a
      complex that could be isolated by gel filtration. Electron micrographs of
      negatively stained ClpXP preparations showed side views of 1:1 and 2:1 ClpXP
      complexes in which ClpP was flanked on either one or both sides by a ring of
      ClpX. Thus, as was seen for ClpAP, a symmetry mismatch exists in the bonding
      interactions between the seven-membered rings of ClpP and the six-membered rings
      of ClpX. Competition studies showed that ClpA may have a slightly higher affinity
      (approximately 2-fold) for binding to ClpP. Mixed complexes of ClpA, ClpX, and
      ClpP with the two ATPases bound simultaneously to opposite faces of a single ClpP
      molecule were seen by electron microscopy. In the presence of ATP or
      nonhydrolyzable analogs of ATP, ClpXP had nearly the same activity as ClpAP
      against oligopeptide substrates (>10,000 min-1/tetradecamer of ClpP). Thus, ClpX
      and ClpA interactions with ClpP result in structurally analogous complexes and
      induce similar conformational changes that affect the accessibility and the
      catalytic efficiency of ClpP active sites.

PMID- 9575204
TI  - Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid
      A and phospholipid biosynthesis.
AB  - The Escherichia coli msbA gene, first identified as a multicopy suppressor of
      htrB mutations, has been proposed to transport nascent core-lipid A molecules
      across the inner membrane (Polissi, A., and Georgopoulos, C. (1996) Mol.
      Microbiol. 20, 1221-1233). msbA is an essential E. coli gene with high sequence
      similarity to mammalian Mdr proteins and certain types of bacterial ABC
      transporters. htrB is required for growth above 32 degreesC and encodes the
      lauroyltransferase that acts after Kdo addition during lipid A biosynthesis
      (Clementz, T., Bednarski, J., and Raetz, C. R. H. (1996) J. Biol. Chem. 271,
      12095-12102). By using a quantitative new 32Pi labeling technique, we demonstrate
      that hexa-acylated species of lipid A predominate in the outer membranes of wild
      type E. coli labeled for several generations at 42 degreesC. In contrast, in htrB
      mutants shifted to 42 degreesC for 3 h, tetra-acylated lipid A species and
      glycerophospholipids accumulate in the inner membrane. Extra copies of the cloned
      msbA gene restore the ability of htrB mutants to grow at 42 degreesC, but they do
      not increase the extent of lipid A acylation. However, a significant fraction of
      the tetra-acylated lipid A species that accumulate in htrB mutants are
      transported to the outer membrane in the presence of extra copies of msbA. E.
      coli strains in which msbA synthesis is selectively shut off at 42 degreesC
      accumulate hexa-acylated lipid A and glycerophospholipids in their inner
      membranes. Our results support the view that MsbA plays a role in lipid A and
      possibly glycerophospholipid transport. The tetra-acylated lipid A precursors
      that accumulate in htrB mutants may not be transported as efficiently by MsbA as
      are penta- or hexa-acylated lipid A species.

PMID- 9575206
TI  - Genetic and biochemical studies establish that the fungicidal effect of a fully
      depeptidized inhibitor of Cryptococcus neoformans myristoyl-CoA:protein N
      myristoyltransferase (Nmt) is Nmt-dependent.
AB  - Cryptococcus neoformans is a fungal pathogen that causes chronic meningitis in
      10% of patients with AIDS. Genetic and biochemical studies were conducted to
      determine whether myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a target
      for development of a new class of fungicidal drugs. A single copy of a
      conditional lethal C. neoformans NMT allele was introduced into the fungal genome
      by homologous recombination. The allele (nmt487D) produces temperature-sensitive
      myristic acid auxotrophy. This phenotype is due, in part, to under-myristoylation
      of a cellular ADP ribosylation factor (Arf) and can be rescued by forced
      expression of human Nmt. Two isogenic strains with identical growth kinetics at
      35 degreesC were used to test the biological effects of an Nmt inhibitor. CPA8
      contained a single copy of wild type C. neoformans NMT. HMC1 contained nmt487D
      plus 10 copies of human NMT. Since a single copy of nmt487D will not support
      growth at 35 degreesC, survival of HMC1 depends upon its human Nmt. ALYASKLS-NH2,
      an inhibitor derived from an Arf, was fully depeptidized: p-[(2-methyl-1-imidazol
      1-yl)butyl]phenyl-acetyl was used to represent the GLYA tetrapeptide, whereas
      SKLS was replaced with a chiral tyrosinol scaffold. Kinetic studies revealed Ki
      (app) values of 1.8 +/- 1 and 9 +/- 2.4 microM for purified fungal and human
      Nmts, respectively. The minimal inhibitory concentration of the compound was 2
      fold lower for CPA8 compared with HMC1. A single dose of 100 microM produced a 5
      fold greater inhibition of protein synthesis in CPA8 versus HMC1. The strain
      specificity of these responses indicates that the fungicidal effect was Nmt
      dependent. These two strains may be useful for screening chemical libraries for
      Nmt-based fungicidal compounds with relatively little activity against the human
      enzyme.

PMID- 9575207
TI  - Properties of PC4 and an RNA polymerase II complex in directing activated and
      basal transcription in vitro.
AB  - A human RNA polymerase II (pol II) complex was isolated from a HeLa-derived cell
      line that conditionally expresses an epitope-tagged RPB9 subunit of human pol II.
      The isolated FLAG-tagged pol II complex (f:pol II) contains a subset of general
      transcription factors but is devoid of TFIID and TFIIA. In conjunction with TATA
      binding protein (TBP) or TFIID, f:pol II is able to mediate both basal and
      activated transcription by Gal4-VP16 when a transcriptional coactivator PC4 is
      also provided. Interestingly, PC4, in the absence of a transcriptional activator,
      actually functions as a repressor to inhibit basal transcription. Remarkably, TBP
      is able to mediate activator function in this transcription system. The presence
      of TBP-associated factors, however, helps overcome PC4 repression and further
      enhance the level of activation mediated by TBP. Alleviation of PC4 repression
      can also be achieved by preincubation of the transcriptional components with the
      DNA template. Sarkosyl disruption of preinitiation complex formation further
      illustrates that PC4 can only inhibit transcription prior to the assembly of a
      functional preinitiation complex. These results suggest that PC4 represses basal
      transcription by preventing the assembly of a functional preinitiation complex,
      but it has no effect on the later steps of the transcriptional process.

PMID- 9575208
TI  - Identification and characterization of a tannic acid-responsive negative
      regulatory element in the mouse mammary tumor virus promoter.
AB  - Tannic acid, which comprises polyphenolic compounds from tea leaves, suppresses
      the glucocorticoid-induced gene expression of mouse mammary tumor virus (MMTV)
      integrated into 34I cells. To investigate whether this suppression is due to
      promoter responsiveness to tannic acid, we performed chloramphenicol
      acetyltransferase analysis transfecting a MMTV promoter containing a
      chloramphenicol acetyltransferase expression vector into mouse fibroblast L929
      cells. Deletion analysis of the promoter region revealed that a 50-base pair (bp)
      region located downstream of the TATA element is responsible for the suppressive
      effect of tannic acid. The tannic acid-sensitive suppressibility was introduced
      into a thymidine kinase promoter by inserting the 50-bp region into the region on
      the 5'-upstream side of the promoter. Detailed point mutation analyses revealed
      that two elements, a 13-bp element and an ACTG motif in the 50-bp region,
      contribute to tannic acid sensitivity and promoter repressibility, respectively.
      Interestingly, this repressive ACTG motif is found in the human immunodeficiency
      virus promoter, the activity of which is also suppressed by tannic acid (Uchiumi,
      F., Maruta, H., Inoue, J., Yamamoto, T., and Tanuma, S. (1996) Biochem. Biophys.
      Res. Commun. 220, 411-417). Furthermore, electrophoretic mobility shift analysis
      revealed that a protein factor(s) in nuclear extracts from L929 cells binds to
      the 50-bp region in a sequence-specific manner and that the amount of DNA-protein
      complex is increased by tannic acid treatment. Moreover, the negative regulatory
      sequence ACTG and the tannic acid-sensitive 13-bp element in this region were
      shown to be responsible for the formation of the DNA-protein complex by
      electrophoretic mobility shift analysis and footprint analyses. These findings
      suggest that the suppressive effect of tannic acid on MMTV gene expression is
      mediated by a protein factor(s) that binds to the negative regulatory element
      containing the common ACTG motif in a cooperative manner with the tannic acid
      sensitive 13-bp element.

PMID- 9575209
TI  - Complementation analysis of mutants of 1-aminocyclopropane- 1-carboxylate
      synthase reveals the enzyme is a dimer with shared active sites.
AB  - The pyridoxal phosphate-dependent enzyme 1-aminocyclopropane-1-carboxylate
      synthase (ACS, EC 4.4.1.14) catalyzes the rate-limiting step in the ethylene
      biosynthetic pathway. ACS shares the conservation of 11 invariant residues with a
      family of aminotransferases that includes aspartate aminotransferase. Site
      directed mutagenesis on two of these residues, Tyr-92 and Lys-278, in the tomato
      isoenzyme Le-ACS2 greatly reduces enzymatic activity, indicating their importance
      in catalysis. These mutants have been used in complementation experiments either
      in vivo in Escherichia coli or in an in vitro transcription/translation assay to
      study whether the enzyme functions as a dimer. When the Y92L mutant is
      coexpressed with the K278A mutant protein, there is partial restoration of enzyme
      activity, suggesting that the mutant proteins can dimerize and form active
      heterodimers. Coexpressing a double mutant with the wild-type protein reduces
      wild-type activity, indicating that inactive heterodimers are formed between the
      wild-type and the double mutant protein subunits. Furthermore, hybrid
      complementation shows that another tomato isoenzyme, Le-ACS4, can dimerize and
      that Le-ACS2 and Le-ACS4 have limited capacity for heterodimerization. The data
      suggest that ACS functions as a dimer with shared active sites.

PMID- 9575210
TI  - Function-structure studies and identification of three enzyme domains involved in
      the catalytic activity in rat hepatic squalene synthase.
AB  - Rat hepatic squalene synthase (RSS, EC 2.5.1.21) contains three conserved
      sections, A, B, and C, that were proposed to be involved in catalysis (McKenzie,
      T. L., Jiang, G., Straubhaar, J. R., Conrad, D., and Shechter, I. (1992) J. Biol.
      Chem. 267, 21368-21374). Here we use the high expression vector pTrxRSS and site
      directed mutagenesis to determine the specific residues in these sections that
      are essential for the two reactions catalyzed by RSS. Section C mutants F288Y,
      F288L, F286Y, F286W, F286L, Q293N, and Q283E accumulate presqualene diphosphate
      (PSPP) from trans-farnesyl diphosphate (FPP) with reduced production of squalene.
      F288L, which retains approximately 50% first step activity, displays only
      residual activity (0.2%) in the production of squalene from either FPP or PSPP.
      Substitution of either Phe288 or Phe286 with charged residues completely
      abolishes the enzyme activity. Thus, F288W, F288D, F288R, F286D, and F286R cannot
      produce squalene from either FPP or PSPP. All single residue mutants in Section
      A, except Tyr171, retain most of the RSS activity, with no detectable
      accumulation of PSPP in an assay mixture complete with NADPH. Y171F, Y171S, and
      Y171W are all inactive. Section B, which binds the diphosphate moieties of the
      allylic diphosphate subtrates, contains four negatively charged residues: Glu222,
      Glu226, Asp219, and Asp223. The two Glu residues can be replaced with neutral or
      with positively charged residues without signficantly affecting enzyme activity.
      However, replacement of either Asp residues with Asn eliminates all but a
      residual level of activity, and substitution with Glu abolishes all activity.
      These results indicate that 1) Section C, in particular Phe288, may be involved
      in the second step of catalysis, 2) Tyr171 of Section A is essential for
      catalysis, most likely for the first reaction, 3) the two Asp residues in Section
      B are essential for the activity and most likely bind the substrate via magnesium
      salt bridges. Based on these results, a mechanism for the first reaction is
      proposed.

PMID- 9575211
TI  - Differential transcriptional regulation of the human squalene synthase gene by
      sterol regulatory element-binding proteins (SREBP) 1a and 2 and involvement of 5'
      DNA sequence elements in the regulation.
AB  - Transcription of the human squalene synthase (HSS) gene is regulated by
      variations in the level of cellular cholesterol. Three regulatory elements in the
      HSS promoter region are known to be involved in the regulation: 1) a modified
      sterol regulatory element (SRE) 1 (HSS-SRE-1), 2) an inverted SRE-3 (Inv-SRE-3),
      3) an inverted Y box (Inv-Y-Box). We report here the regulatory role of distinct
      cis-elements in the HSS promoter by using mutants of an HSS-luciferase promoter
      reporter. The activity of a wild-type promoter reporter transiently transfected
      into HepG-2 cells is increased by sterol depletion of the cells or by
      coexpression of mature forms of the SRE-binding proteins (SREBP) 1a and SREBP-2.
      Differential activation by SREBP-1a and SREBP-2 of the reporter gene mutated at
      various regions of the promoter is observed. Mutation of either the HSS-SRE-1 or
      the Inv-SRE-3 sequence diminished the activation by SREBP-1a and by sterol
      depletion but did not affect the activation by SREBP-2. Simultaneous mutations of
      both of these sequences almost completely abolished activation of the promoter by
      SREBP-1a or by sterol depletion, but activation by SREBP-2 was retained at 70%.
      Mutation of the Inv-Y-Box sequence element decreased the activity of the promoter
      by 50% or more, and if mutated together with both SREs, the activation was almost
      completely abolished. Mutation of any single GC box of the two located at -40 to 
      57 did not affect activity, whereas simultaneous mutation of the two decreased
      activation by SREBP-2 by 60%, by lipid depletion by 20%, and had no effect on the
      activation by SREBP-1a. A Y box motif at -159 to -166 and an SRE-like sequence
      element (SRE-1(8/10)) at position -101 to -108 are also involved in the sterol
      regulation. These results indicate that the complex sterol-mediated
      transcriptional regulation of the HSS gene is due to the presence of multiple
      copies of diverse cis elements in the HSS promoter. The differential activation
      of the HSS promoter may point to specific role of the SREBPs in
      cholesterogenesis.

PMID- 9575212
TI  - Cloning and expression of cDNA encoding rat liver 60-kDa lysophospholipase
      containing an asparaginase-like region and ankyrin repeat.
AB  - Mammalian tissues contain small form and large form lysophospholipases. Here we
      report the cloning, sequence, and expression of cDNA encoding the latter form of
      lysophospholipase using antibody raised against the enzyme purified from rat
      liver supernatant (Sugimoto, H., and Yamashita, S. (1994) J. Biol. Chem. 269,
      6252-6258). The 2,539-base pair cDNA encoded 564 amino acid residues with a
      calculated Mr of 60,794. The amino-terminal two-thirds of the deduced amino acid
      sequence significantly resembled Escherichia coli asparaginase I with the
      putative asparaginase catalytic triad Thr-Asp-Lys and was followed by leucine
      zipper motif. The carboxyl-terminal region carried ankyrin repeat. When the cDNA
      was transfected into HEK293 cells, not only lysophospholipase activity but also
      asparaginase and platelet-activating factor acetylhydrolase activities were
      expressed. Reverse transcription-polymerase chain reaction revealed that the
      transcript occurred at high levels in liver and kidney but was hardly detectable
      in lung and heart from which large form lysophospholipases had been purified,
      suggesting the presence of multiple forms of large form lysophospholipase in
      mammalian tissues.

PMID- 9575213
TI  - Role for the Salmonella flavohemoglobin in protection from nitric oxide.
AB  - Hemoglobin homologs are being identified in an expanding number of unicellular
      prokaryotic and eukaryotic organisms. Many of these hemoglobins are twodomain
      proteins that possess a flavin-containing reductase in their C terminus.
      Determination of a function for these flavohemoglobins has been elusive. A
      Salmonella typhimurium strain harboring a deletion in the flavohemoglobin gene
      shows no difference in growth under oxidative stress conditions but displays an
      increased sensitivity to acidified nitrite and S-nitrosothiols, both of which
      produce nitric oxide. The effect is seen aerobically or anaerobically, indicating
      that oxygen is not required for flavohemoglobin function. These results suggest a
      role for the bacterial flavohemoglobins that is independent of oxygen metabolism
      and provide evidence for a bacterial route of protection from nitric oxide that
      is distinct from oxidative stress responses.

PMID- 9575214
TI  - Amyloid protein precursor stimulates excitatory amino acid transport.
      Implications for roles in neuroprotection and pathogenesis.
AB  - Excitatory neurotransmitters such as glutamate are required for the normal
      functioning of the central nervous system but can trigger excitotoxic neuronal
      injury if allowed to accumulate to abnormally high levels. Their extracellular
      levels are controlled primarily by transmitter uptake into astrocytes. Here, we
      demonstrate that the amyloid protein precursor may participate in the regulation
      of this important process. The amyloid protein precursor has been well conserved
      through evolution, and a number of studies indicate that it may function as an
      endogenous excitoprotectant. However, the mechanisms underlying this
      neuroprotective capacity remain largely unknown. At moderate levels of
      expression, human amyloid protein precursors increased glutamate/aspartate uptake
      in brains of transgenic mice, with the 751-amino acid isoform showing greater
      potency than the 695-amino acid isoform. Cerebral glutamate/aspartate transporter
      protein levels were higher in transgenic mice than in non-transgenic controls,
      whereas transporter mRNA levels were unchanged. Amyloid protein precursor
      dependent stimulation of aspartate uptake by cultured primary astrocytes was
      associated with increases in protein kinase A and C activity and could be blocked
      by inhibitors of these kinases. The stimulation of astroglial excitatory amino
      acid transport by amyloid protein precursors could protect the brain against
      excitotoxicity and may play an important role in neurotransmission.

PMID- 9575215
TI  - Involvement of heme in the degradation of iron-regulatory protein 2.
AB  - Iron-regulatory proteins (IRPs) recognize and bind to specific RNA structures
      called iron-responsive elements. Mediation of these binding interactions by iron
      and iron-containing compounds regulates several post-transcriptional events
      relevant to iron metabolism. There are two known IRPs, IRP1 and IRP2, both of
      which can respond to iron fluxes in the cell. There is ample evidence that IRP1
      is converted by iron to cytoplasmic aconitase in vivo. It has also been shown
      that, under certain conditions, a significant fraction of IRP1 is degraded in
      cells exposed to iron or heme. Studies have shown that the degradation of IRP1
      that is induced by iron can be inhibited by either desferrioxamine mesylate (an
      iron chelator) or succinyl acetone (an inhibitor of heme synthesis), whereas the
      degradation induced by heme cannot. This suggests that heme rather than iron is
      responsible for this degradation. Several laboratories have shown that IRP2 is
      also degraded in cells treated with iron salts. We now show evidence suggesting
      that this IRP2 degradation may be mediated by heme. Thus, in experiments
      analogous to those used previously to study IRP1, we find that IRP2 is degraded
      in rabbit fibroblast cells exposed to heme or iron salts. However, as shown
      earlier with IRP1, both desferrioxamine mesylate and succinyl acetone will
      inhibit the degradation of IRP2 induced by iron but not that induced by heme.

PMID- 9575216
TI  - Irreversible inactivation of protein kinase C by glutathione.
AB  - The tripeptide glutathione (GSH) is the predominant low molecular weight thiol
      reductant in mammalian cells. In this report, we show that at concentrations at
      which GSH is typically present in the intracellular milieu, GSH and the oxidized
      GSH derivatives GSH disulfide (GSSG) and glutathione sulfonate each irreversibly
      inactivate up to 100% of the activity of purified Ca2+- and phosphatidylserine
      (PS)-dependent protein kinase C (PKC) isozymes in a concentration-dependent
      manner by a novel nonredox mechanism that requires neither glutathiolation of PKC
      nor the reduction, formation, or isomerization of disulfide bridges within PKC.
      Our evidence for a nonredox mechanism of PKC inactivation can be summarized as
      follows. GSSG antagonized the Ca2+- and PS-dependent activity of purified rat
      brain PKC with the same efficacy (IC50 = 3 mM) whether or not the reductant
      dithiothreitol was present. Glutathione sulfonate, which is distinguished from
      GSSG and GSH by its inability to undergo disulfide/thiol exchange reactions, was
      as effective as GSSG in antagonizing Ca2+- and PS-dependent PKC catalysis. The
      irreversibility of the inactivation mechanism was indicated by the stability of
      the inactivated form of PKC to dilution and extensive dialysis. The inactivation
      mechanism did not involve the nonspecific phenomena of denaturation and
      aggregation of PKC because it obeyed pseudo-first order kinetics and because the
      hinge region of PKC-alpha remained a preferential target of tryptic attack
      following GSH inactivation. The selectivity of GSH in the inactivation of PKC was
      also indicated by the lack of effect of the tripeptides Tyr-Gly-Gly and Gly-Ala
      Gly on the activity of PKC. Furthermore, GSH antagonism of the Ser/Thr kinase
      casein kinase 2 was by comparison weak (<25%). Inactivation of PKC-alpha was not
      accompanied by covalent modification of the isozyme by GSH or other irreversible
      binding interactions between PKC-alpha and the tripeptide, but it was associated
      with an increase in the susceptibility of PKC-alpha to trypsinolysis. Treatment
      of cultured rat fibroblast and human breast cancer cell lines with N
      acetylcysteine resulted in a substantial loss of Ca2+- and PS- dependent PKC
      activity in the cells within 30 min. These results suggest that GSH exerts
      negative regulation over cellular PKC isozymes that may be lost when oxidative
      stress depletes the cellular GSH pool.

PMID- 9575218
TI  - Purification and characterization of rat kidney sphingosine kinase.
AB  - Sphingosine kinase catalyzes the formation of the bioactive sphingolipid
      metabolite sphingosine 1-phosphate, which plays important roles in numerous
      physiological processes, including growth, survival, and motility. We have
      purified rat kidney sphingosine kinase 6 x 10(5)-fold to apparent homogeneity.
      The purification procedure involved ammonium sulfate precipitation followed by
      chromatography on an anion exchange column. Partially purified sphingosine kinase
      was found to be stabilized by the presence of high salt, and thus, a scheme was
      developed to purify sphingosine kinase using sequential dye-ligand chromatography
      steps (since the enzyme bound to these matrices even in the presence of salt)
      followed by EAH-Sepharose chromatography. This 385-fold purified sphingosine
      kinase bound tightly to calmodulin-Sepharose and could be eluted in high yield
      with EGTA in the presence of 1 M NaCl. After concentration, the calmodulin eluate
      was further purified by successive high pressure liquid chromatography
      separations on hydroxylapatite, Mono Q, and Superdex 75 gel filtration columns.
      Purified sphingosine kinase has an apparent molecular mass of approximately 49
      kDa under denaturing conditions on SDS-polyacrylamide gel, which is similar to
      the molecular mass determined by gel filtration, suggesting that the active form
      is a monomer. Sphingosine kinase shows substrate specificity for D-erythro
      sphingosine and does not catalyze the phosphorylation of phosphatidylinositol,
      diacylglycerol, ceramide, DL-threo-dihydrosphingosine, or N,N
      dimethylsphingosine. However, the latter two sphingolipids were potent
      competitive inhibitors. With sphingosine as substrate, the enzyme had a broad pH
      optimum of 6.6-7.5 and showed Michaelis-Menten kinetics, with Km values of 5 and
      93 microM for sphingosine and ATP, respectively. This study provides the basis
      for molecular characterization of a key enzyme in sphingolipid signaling.

PMID- 9575217
TI  - Jak2-Stat5 interactions analyzed in yeast.
AB  - Many cytokine receptors employ Janus protein tyrosine kinases (Jaks) and signal
      transducers and activators of transcription (Stats) for nuclear signaling. Here,
      we have established yeast strains in which an autoactivated Jak2 kinase induces
      tyrosine phosphorylation, dimerization, nuclear translocation, and DNA binding of
      a concomitantly expressed Stat5 protein. Transcriptional activity of Stat5 on a
      stably integrated, Stat-dependent reporter gene required the C-terminal fusion of
      the VP16 transactivation domain. In such yeast strains, the interaction between
      Jak2 and Stat5 was analyzed without interference by other mammalian proteins
      involved in regulating Jak-Stat signaling, and mutant versions of both proteins
      were analyzed for their ability to productively interact. Complexes between Jak2
      and Stat5 were found to be stable under stringent co-immunoprecipitation
      conditions. Deletion of the Jak homology regions 2-7 (JH2-JH7) of Jak2, leaving
      only the kinase domain (JH1) intact, reduced the ability of the kinase to
      phosphorylate Stat5, whereas deletion of the JH2 domain caused an increased
      enzymatic activity. A site-directed R618K mutation in the Stat5 SH2 domain
      abolished the phosphorylation by Jak2, while deletion of the C terminus led to
      Stat5 hyperphosphorylation. A single phosphotyrosine-SH2 domain interaction was
      sufficient for the dimerization of Stat5, but such dimers bound to DNA very
      inefficiently. Together, our data show that yeast cells are appropriate tools for
      studying Jak-Stat or Stat-Stat interactions. Our mutational analysis suggests
      that the Stat5 SH2 domain is essential for the interaction with Jak2 and that the
      kinase domain of Jak2 is sufficient for Jak2-Stat5 interaction. Therefore, the
      Jak kinase domain may be all that is needed to cause Stat phosphorylation in
      situations where receptor docking is dispensable.

PMID- 9575219
TI  - Endothelin-induced apoptosis of A375 human melanoma cells.
AB  - Endothelin-1 (ET-1) inhibited serum-dependent growth of asynchronized A375 human
      melanoma cells, and the growth inhibitory effect was markedly enhanced when ET-1
      was applied to the cells synchronized at G1/S boundary by double thymidine
      blocks. Flow cytometric analysis revealed that ET-1 did not inhibit the cell
      cycle progression after the release of the block but caused a significant
      increase of the hypodiploid cell population that is characteristic of apoptotic
      cell death. ET-1-induced apoptosis was confirmed by the appearance of chromatin
      condensation on nuclear staining and DNA fragmentation on gel electrophoresis.
      The increase in the hypodiploid cell peak was manifest within 16 h of exposure to
      5 nM ET-1. Within the same time range, ET-1 caused actin reorganization and
      drastic morphological changes of the surviving cells from epithelioid to an
      elongated bipolar shape. These phenotypical changes were preceded by ET-1-induced
      increase and nuclear accumulation of the tumor suppressor protein p53. All of
      these effects of ET-1 were mediated by ETB via a pertussis toxin-sensitive G
      protein. Flow cytometric analysis with fluorescent dye-labeled ET-1 revealed up
      regulation of ETB expressed by the cells in G1/early S phases, and overexpression
      of the receptor protein by cDNA microinjection conferred the responsiveness (both
      apoptosis and morphological changes) to ET-1 irrespective of the position of the
      cell in the cell cycle. These results indicated the presence of ETB-mediated
      signaling pathways to apoptotic cell machinery and cytoskeletal organization.
      Furthermore, the densities of ETB expressed by individual A375 melanoma cells
      appeared to be regulated by a cell cycle-dependent mechanism, and the receptor
      density can be a limiting factor to control the apoptotic and cytoskeletal
      responses of the cells to ET-1. Although the molecular mechanisms remain to be
      elucidated, these findings added a new dimension to the diverse biological
      activities of ETs and also indicated a novel mechanism to control the
      responsiveness of the cell to the peptides.

PMID- 9575220
TI  - Activation of the cytochrome c gene by electrical stimulation in neonatal rat
      cardiac myocytes. Role of NRF-1 and c-Jun.
AB  - Activation of cytochrome c (cyt c) transcription in electrically stimulated
      neonatal rat cardiac myocytes is preceded by transient expression of the
      activating protein-1 family of transcription factors, c-Fos, c-Jun, and JunB, as
      well as nuclear respiratory factor-1 (NRF-1). Mutations in either the NRF-1 or in
      the two cyclic AMP response elements on the cyt c promoter significantly reduce
      cyt c promoter activation produced either by electrical stimulation (Xia, Y.,
      Buja, L. M., Scarpulla, R. C., and McMillin, J. B. (1997) Proc. Natl. Acad. Sci.
      U. S. A. 94, 11399-11404) or by transfection of c-jun into nonpaced cardiac
      myocytes. Electrical stimulation of cardiac myocytes activates the c-Jun N
      terminal kinase (McDonough, P. M., Hanford, D. S., Sprenkle, A. B., Mellon, N.
      R., and Glembotski, C. C. (1997) J. Biol. Chem. 272, 24046-24053) so that the
      fold-activation of the cyt c promoter is increased by pacing when either c-jun or
      c-fos/c-jun were cotransfected. Physical association of NRF-1 protein with the
      NRF-1 enhancer element and of c-Jun with the cyclic AMP response element binding
      sites on the cyt c promoter was demonstrated by gel shift competition assays and
      by antibody super shifts. This is the first demonstration that induction of NRF-1
      and c-Jun by pacing of cardiac myocytes directly mediates cyt c gene expression
      and mitochondrial proliferation in response to hypertrophic stimuli in the heart.

PMID- 9575221
TI  - HAT1 and HAT2 proteins are components of a yeast nuclear histone
      acetyltransferase enzyme specific for free histone H4.
AB  - We have analyzed the histone acetyltransferase enzymes obtained from a series of
      yeast hat1, hat2, and gcn5 single mutants and hat1,hat2 and hat1,gcn5 double
      mutants. Extracts prepared from both hat1 and hat2 mutant strains specifically
      lack the following two histone acetyltransferase activities: the well known
      cytoplasmic type B enzyme and a free histone H4-specific histone
      acetyltransferase located in the nucleus. The catalytic subunits of both
      cytoplasmic and nuclear enzymes have identical molecular masses (42 kDa), the
      same as that of HAT1. However, the cytoplasmic complex has a molecular mass (150
      kDa) greater than that of the nuclear complex (110 kDa). The possible functions
      of HAT1 and HAT2 in the yeast nucleus are discussed. In addition, we have
      detected a yeast histone acetyltransferase not previously described, designated
      HAT-A4. This enzyme is located in the nucleus and is able to acetylate free and
      nucleosome-bound histones H3 and H4. Finally, we show that the hat1, gcn5 double
      mutant is viable and does not exhibit a new phenotype, thus suggesting the
      existence of several histone acetyltransferases with overlapping functions.

PMID- 9575222
TI  - Novel hydrogen peroxide metabolism in suspension cells of Scutellaria baicalensis
      Georgi.
AB  - We identified a rapid and novel system to effectively metabolize a large amount
      of H2O2 in the suspension cells of Scutellaria baicalensis Georgi. In response to
      an elicitor, the cells immediately initiate the hydrolysis of baicalein 7-O-beta
      D-glucuronide by beta-glucuronidase, and the released baicalein is then quickly
      oxidized to 6,7-dehydrobaicalein by peroxidases. Hydrogen peroxide is effectively
      consumed during the peroxidase reaction. The beta-glucuronidase inhibitor,
      saccharic acid 1,4-lactone, significantly reduced the H2O2-metabolizing ability
      of the Scutellaria cells, indicating that beta-glucuronidase, which does not
      catalyze the H2O2 degradation, plays an important role in the H2O2 metabolism. As
      H2O2-metabolizing enzymes, we purified two peroxidases using ammonium sulfate
      precipitation followed by sequential chromatography on CM-cellulose and
      hydroxylapatite. Both peroxidases show high H2O2-metabolizing activity using
      baicalein, whereas other endogenous flavones are not substrates of the peroxidase
      reaction. Therefore, baicalein predominantly contributed to H2O2 metabolism.
      Because beta-glucuronidase, cell wall peroxidases, and baicalein pre-exist in
      Scutellaria cells, their constitutive presence enables the cells to rapidly
      induce the H2O2-metabolizing system.

PMID- 9575223
TI  - ATPase and multidrug transport activities of the overexpressed yeast ABC protein
      Yor1p.
AB  - The Saccharomyces cerevisiae genome encodes 15 full-size ATP binding cassette
      transporters (ABC), of which PDR5, SNQ2, and YOR1 are known to be regulated by
      the transcription factors Pdr1p and Pdr3p (pleiotropic drug resistance). We have
      identified two new ABC transporter-encoding genes, PDR10 and PDR15, which were up
      regulated by the PDR1-3 mutation. These genes, as well as four other ABC
      transporter-encoding genes, were deleted in order to study the properties of
      Yor1p. The PDR1-3 gain-of-function mutant was then used to overproduce Yor1p up
      to 10% of the total plasma membrane proteins. Overexpressed Yor1p was
      photolabeled by [gamma-32P]2', 3'-O-(2,4,6-trinitrophenyl)-8-azido-ATP (K0.5 = 45
      microM) and inhibited by ATP (KD = 0.3 mM) in plasma membranes. Solubilization
      and partial purification on sucrose gradient allowed to detect significant Yor1p
      ATP hydrolysis activity (approximately 100 nmol of Pi.min-1.mg-1). This activity
      was phospholipid-dependent and sensitive to low concentrations of vanadate (I50 =
      0.3 microM) and oligomycin (I50 = 8.5 microg/ml). In vivo, we observed a
      correlation between the amount of Yor1p in the plasma membrane and the level of
      resistance to oligomycin. We also demonstrated that Yor1p drives an energy
      dependent, proton uncoupler-insensitive, cellular extrusion of rhodamine B.
      Furthermore, cells lacking both Yor1p and Pdr5p (but not Snq2p) showed increased
      accumulation of the fluorescent derivative of 1-myristoyl-2-[6
      (NBD)aminocaproyl]phosphatidylethanolamine. Despite their different topologies,
      both Yor1p and Pdr5p mediated the ATP-dependent translocation of similar drugs
      and phospholipids across the yeast cell membrane. Both ABC transporters exhibit
      ATP hydrolysis in vitro, but Pdr5p ATPase activity is about 15 times higher than
      that of Yor1p, which may indicate mechanistic or regulatory differences between
      the two enzymes.

PMID- 9575224
TI  - Distinct involvement of beta3 integrin cytoplasmic domain tyrosine residues 747
      and 759 in integrin-mediated cytoskeletal assembly and phosphotyrosine signaling.
AB  - We have investigated the structural requirements of the beta3 integrin subunit
      cytoplasmic domain necessary for tyrosine phosphorylation of focal adhesion
      kinase (FAK) and paxillin during alphav beta3-mediated cell spreading. Using CHO
      cells transfected with various beta3 mutants, we demonstrate a close correlation
      between alphav beta3-mediated cell spreading and tyrosine phosphorylation of FAK
      and paxillin, and highlight a distinct involvement of the NPLY747 and NITY759
      motifs in these signaling processes. Deletion of the NITY759 motif alone was
      sufficient to completely prevent alphav beta3-dependent focal contact formation,
      cell spreading, and FAK/paxillin phosphorylation. The single Y759A substitution
      induced a strong inhibitory phenotype, while the more conservative, but still
      phosphorylation-defective, Y759F mutation restored wild type receptor function.
      Alanine substitution of the highly conserved Tyr747 completely abolished alphav
      beta3-dependent formation of focal adhesion plaques, cell spreading, and
      FAK/paxillin phosphorylation, whereas a Y747F substitution only partially
      restored these events. As none of these mutations affected receptor-ligand
      interaction, our results suggest that the structural integrity of the NITY759
      motif, rather than the phosphorylation status of Tyr759 is important for beta3
      mediated cytoskeleton reorganization and tyrosine phosphorylation of FAK and
      paxillin, while the presence of Tyr at residue 747 within the NPLY747 motif is
      required for optimal beta3 post-ligand binding events.

PMID- 9575225
TI  - Transcriptional regulation of interleukin-1beta gene by interleukin-1beta itself
      is mediated in part by Oct-1 in thymic stromal cells.
AB  - Interleukin (IL)-1 is involved in many processes, including thymic development.
      However, control of IL-1 expression in thymic-derived stromal cells (TSC) has not
      been reported. We found that IL-1beta increased steady-state mRNA levels for IL
      1alpha and IL-1beta in TSC-936 and TSC-2C4 cells; stability was not a major
      determinant of this effect. To study transcriptional regulation of IL-1beta, we
      functionally characterized 4 kilobase pairs of the 5'-flanking region and first
      intron of the bovine IL-1beta gene. The -470/+14 fragment was sufficient to
      confer maximal responsiveness to IL-1beta upon transfection into these cell
      lines. Progressive 5' deletions identified several IL-1beta-responsive regions,
      including -308 to -226, which we further characterized. Electrophoretic mobility
      shift and supershift analyses showed that IL-1beta induced the ability to form
      multiple protein complexes with -261/-226 and that one of these contained nuclear
      factor Oct-1. A competitor containing a mutated Oct consensus site failed to
      compete not only for this complex but others as well, suggesting that this
      sequence regulates binding of other proteins to this region. Functional analysis
      confirmed that this element was essential for maximal induction of transcription.
      These findings document a heretofore undescribed mechanism utilized by TSC for
      regulation of IL-1beta transcription by IL-1beta itself.

PMID- 9575227
TI  - Stability determinants are localized to the 3'-untranslated region and 3'-coding
      region of the neurofilament light subunit mRNA using a tetracycline-inducible
      promoter.
AB  - The tetracycline-responsive expression system of Bujard was used to compare rates
      of decay of wild-type and mutant neurofilament (NF) light subunit (NF-L) mRNAs.
      Optimal conditions for activation and inactivation of the target transgene were
      determined using a luciferase reporter gene. Analyses of mRNA stability were
      thereupon conducted on cells that were doubly transfected with transactivator and
      inducible target genes and derived from pooled clones of transfected cells. Rates
      of mRNA decay were compared upon inactivation of the transgenes after high levels
      of mRNA had been induced. Deletion of the 445-nucleotide (nt) 3'-untranslated
      region (3'-UTR) (L/++(+)-) or 527 nt of the 3'-coding region (3'-CR) (L/++-+)
      increased the stability of NF-L mRNA compared with the full-length (L/++(++))
      transcript in neuronal (N2a and P19 cells) and non-neuronal (L cells) lines.
      Deletion of both the 3'-UTR and 3'-CR (L/++--) led to a further stabilization of
      the transcript. A major stability determinant was then localized to a 68-nt
      sequence that forms the junction between the 3'-CR and 3'-UTR of NF-L and is the
      binding site of a unique ribonucleoprotein complex (Canete-Soler, R., Schwartz,
      M. L., Hua, Y., and Schlaepfer, W. W. (1998) J. Biol. Chem. 273, 12655-12661).
      The studies establish a novel system for mapping determinants of mRNA stability
      and have applied the system to localize determinants that regulate the stability
      of the NF-L mRNA.

PMID- 9575226
TI  - Glycosaminoglycan sulfation in human osteoarthritis. Disease-related alterations
      at the non-reducing termini of chondroitin and dermatan sulfate.
AB  - Chondroitin lyase products of aggrecan and small proteoglycans from normal and
      osteoarthritic cartilages were analyzed for chain internal Deltadisaccharides and
      terminal mono- or disaccharides. Chondroitin and dermatan sulfate chains from
      arthritic cartilages were of essentially normal size and internal sulfation but
      had significantly altered sulfation of the terminal residues. Whereas in normal
      cartilage, approximately 60% of terminal GalNAc4S was 4, 6-disulfated, it was
      reduced to approximately 30% in osteoarthritic cartilage. This is most likely due
      to a lower terminal GalNAc4, 6S-disulfotransferase activity and reveals that
      metabolic changes in osteoarthritis can affect this distinct sulfation step
      during chondroitin and dermatan sulfate synthesis. GlcAbeta1,3GalNAc6S-, the
      mimotope for antibody 3B3(-), was present on approximately 8 and approximately
      10% of chains from normal and osteoarthritic cartilages, respectively. 3B3(-)
      assayed by immunodot blot was within the normal range for most osteoarthritic
      samples, with only 5 of 24 displaying elevated reactivity. This resulted not from
      a higher content of mimotope, but possibly from other structural changes in the
      proteoglycan that increase mimotope reactivity. In summary, chemical
      determination of sulfation isomers at the non-reducing termini of chondroitin and
      dermatan sulfate provides a reliable assay for monitoring proteoglycan metabolism
      not only during normal growth of cartilage but also during remodeling of
      cartilage in osteoarthritis.

PMID- 9575228
TI  - Characterization of ribonucleoprotein complexes and their binding sites on the
      neurofilament light subunit mRNA.
AB  - Levels of neurofilament (NF) gene expression are important determinants of basic
      neuronal properties, but overexpression can lead to motoneuron degeneration in
      transgenic mice. In a companion study (Canete-Soler, R., Schwartz, M. L., Hua,
      Y., and Schlaepfer, W. W. (1998) J. Biol. Chem. 273, 12650-12654), we show that
      levels of NF expression are regulated by altering mRNA stability and that
      stability determinants are present in the 3'-coding region (3'-CR) and 3'
      untranslated region (3'-UTR) of the NF light subunit (NF-L) transcript. This
      study characterizes the ribonucleoprotein complexes that bind to the NF-L mRNA
      when cytoplasmic brain extracts are incubated with radioactive probes. Gel
      retardation assays reveal ribonucleoprotein complexes that are selectively
      competed with poly(C) or poly(U))/poly(A) homoribopolymers and are referred to as
      C-binding and U/A-binding complexes, respectively. The C-binding complex forms on
      the proximal 45 nucleotides of 3'-UTR, but its assembly is markedly enhanced by
      23 nucleotides of flanking 3'-CR sequence. U/A-binding complexes form at multiple
      binding sites in the 3'-CR and 3'-UTR. A pattern of reciprocal binding suggests
      that the C-binding and U/A-binding complexes interact and may compete for common
      components or binding sites. Cross-linking studies reveal unique polypeptides in
      the C-binding and U/A-binding complexes. The findings provide the basis for
      probing mechanisms regulating NF-L mRNA stability and the relationship between NF
      overexpression and motoneuron degeneration in transgenic mice.

PMID- 9575229
TI  - Regulation of the permeability transition pore in skeletal muscle mitochondria.
      Modulation By electron flow through the respiratory chain complex i.
AB  - We have investigated the regulation of the permeability transition pore (PTP), a
      cyclosporin A-sensitive channel, in rat skeletal muscle mitochondria. As is the
      case with mitochondria isolated from a variety of sources, skeletal muscle
      mitochondria can undergo a permeability transition following Ca2+ uptake in the
      presence of Pi. We find that the PTP opening is dramatically affected by the
      substrates used for energization, in that much lower Ca2+ loads are required when
      electrons are provided to complex I rather than to complex II or IV. This
      increased sensitivity of PTP opening does not depend on differences in membrane
      potential, matrix pH, Ca2+ uptake, oxidation-reduction status of pyridine
      nucleotides, or production of H2O2, but is directly related to the rate of
      electron flow through complex I. Indeed, and with complex I substrates only, pore
      opening can be observed when depolarization is induced with uncoupler (increased
      electron flow) but not with cyanide (decreased electron flow). Consistent with
      pore regulation by electron flow, we find that PTP opening is inhibited by
      ubiquinone 0 at concentrations that partially inhibit respiration and do not
      depolarize the inner membrane. These data allow identification of a novel site of
      regulation of the PTP, suggest that complex I may be part of the pore complex,
      and open new perspectives for its pharmacological modulation in living cells.

PMID- 9575230
TI  - Chemical modification of arginines by 2,3-butanedione and phenylglyoxal causes
      closure of the mitochondrial permeability transition pore.
AB  - We have investigated the role of arginine residues in the regulation of the
      mitochondrial permeability transition pore, a cyclosporin A-sensitive inner
      membrane channel. Isolated rat liver mitochondria were treated with the arginine
      specific chemical reagent 2, 3-butanedione or phenylglyoxal, followed by removal
      of excess free reagent. After this treatment, mitochondria accumulated Ca2+
      normally, but did not undergo permeability transition following depolarization, a
      condition that normally triggers opening of the permeability transition pore.
      Inhibition by 2,3-butanedione and phenylglyoxal correlated with matrix pH,
      suggesting that the relevant arginine(s) are exposed to the matrix aqueous phase.
      Inhibition by 2,3-butanedione was potentiated by borate and was reversed upon its
      removal, whereas inhibition by phenylglyoxal was irreversible. Treatment with 2,3
      butanedione or phenylglyoxal after induction of the permeability transition by
      Ca2+ overload resulted in pore closure despite the presence of 0.5 mM Ca2+. At
      concentrations that were fully effective at inhibiting the permeability
      transition, these arginine reagents (i) had no effect on the isomerase activity
      of cyclophilin D and (ii) did not affect the rate of ATP translocation and
      hydrolysis, as measured by the production of a membrane potential upon ATP
      addition in the presence of rotenone. We conclude that reaction with 2,3
      butanedione and phenylglyoxal results in a stable chemical modification of
      critical arginine residue(s) located on the matrix side of the inner membrane,
      which, in turn, strongly favors a closed state of the pore.

PMID- 9575231
TI  - Determination of external loop topology in the serotonin transporter by site
      directed chemical labeling.
AB  - The transmembrane topology of the serotonin transporter (SERT) has been examined
      by measuring the reactivity of selected lysine and cysteine residues with
      extracellular reagents. An impermeant biotinylating reagent, sulfosuccinimidyl 2
      (biotinamido)ethyl-1, 3-dithiopropionate (NHS-SS-biotin), was shown to label SERT
      transiently expressed in cultured cells. Replacement of four lysine residues that
      were predicted to lie in external hydrophilic loops (eK-less) largely prevented
      the biotinylation reaction. Likewise, the cysteine-specific biotinylation reagent
      N-biotinylaminoethylmethanethiosulfonate (MTSEA-biotin) labeled wild type SERT
      but not a mutant in which Cys-109, predicted to lie in the first external loop,
      was replaced with alanine. These two mutant transporters reacted with the
      biotinylating reagents in digitonin-permeabilized cells, demonstrating that the
      abundant lysine and cysteine residues predicted to lie in intracellular
      hydrophilic domains were reactive but not accessible in intact cells. Mutants
      containing a single external lysine at positions 111, 194, 243, 319, 399, 490,
      and 571 reacted more readily with NHS-SS-biotin than did the eK-less mutant.
      Similarly, mutants with a single cysteine at positions 109, 310, 406, 489, and
      564 reacted more readily with MTSEA-biotin than did the C109A mutant. All of
      these mutants were active and therefore likely to be folded correctly. These
      results support the original transmembrane topology and argue against an
      alternative topology proposed recently for the related glycine and gamma
      aminobutyric acid transporters.

PMID- 9575232
TI  - The phylogeny of unicellular, extremely halotolerant cyanobacteria.
AB  - We examined the morphology, physiology, and 16S rRNA gene sequences of three
      culture collection strains and of ten novel isolates of unicellular cyanobacteria
      from hypersaline environments. The strains were morphologically diverse, with
      average cell widths ranging from 2.8 to 10.3 micron. There were single-celled,
      colonial, and baeocyte-forming strains. However, morphological traits were
      markedly variable with culture conditions. In contrast, all strains displayed
      extreme halotolerance (growing close to optimally at above 12% salinity); all
      were obligately marine, euryhaline, and moderately thermophilic; and all shared a
      suite of chemotaxonomic markers including phycobilins, carotenoids, and
      mycosporine-like amino acids. 16S rRNA gene sequence analysis indicated that the
      strains were related to each other. Sequence similarity analysis placed the
      strains in a monophyletic cluster (which we named the Halothece cluster) apart
      from all cultured or uncultured, not extremely halotolerant cyanobacteria whose
      16S rRNA gene sequences are available in public nucleotide sequence databases.
      This represents the first case in which a phylogenetically coherent group of
      cyanobacteria can be defined on the basis of physiology. The Halothece cluster
      contained two subclusters that may be divergent at the generic level, one
      encompassing 12 strains (spanning 5% 16S rRNA gene sequence divergence and named
      the Euhalothece subcluster), and a single deep-branching isolate. Phenotypic
      characterization of the isolates, including morphological, physiological, and
      chemotaxonomic traits, did not distinguish these subclusters and only weakly
      suggested the existence of two separate clades, one encompassing strains of small
      cell size (cell width < 5 m) and another one encompassing strains of larger cell
      size.

PMID- 9575233
TI  - Iron regulates transcription of the Escherichia coli ferric citrate transport
      genes directly and through the transcription initiation proteins.
AB  - Ferric citrate induces transcription of the ferric citrate transport genes
      fecABCDE in Escherichia coli by binding to the outer-membrane receptor protein
      FecA without entering the cell. Replete iron concentrations inhibit transcription
      of the fec transport system via the iron-loaded Fur repressor. Here we show that
      the Fur repressor activated by Mn2+ (used instead of Fe2+) binds to the promoter
      of the regulatory genes fecIR and to the promoter of fecABCDE. DNase I footprint
      analysis revealed that Mn2+-Fur (50 nM) protected 30 nucleotides of the coding
      strand and 24 nucleotides of the noncoding strand of the fecIR promoter. Higher
      amounts of Mn2+-Fur (100 nM) covered 41 nucleotides of the coding strand of the
      fecIR promoter and 38 nucleotides of the coding strand of the fecA promoter. The
      corresponding region of the noncoding strand of the fecA promoter was
      hypersensitive to DNase I. The results of a deletion analysis of the fecA
      promoter supported the previously assigned -35 and -10 regions and nucleotide
      position +11 for FecI-RNA polymerase interaction. Induction of fecIR
      transcription by iron limitation increased fecB-lacZ transcription 3.5-fold,
      whereas under constitutive fecIR transcription, iron limitation increased fecB
      lacZ transcription twofold. The two iron-regulated sites of fec transport gene
      transcription suggest a fast response to sufficient intracellular iron
      concentrations by repression of fecABCDE transcription and a slower adaptation as
      the result of fecIR transcription inhibition.

PMID- 9575234
TI  - Exponential growth of Escherichia coli B/r during its division cycle is
      demonstrated by the size distribution in liquid culture.
AB  - The Collins and Richmond equation was used to analyze the growth of individual
      bacterial cells. Birth size was derived from the size of deeply constricted cells
      in the sample. The analysis was applied to normalized and pooled data from
      electron micrographs of Escherichia coli showing that cellular length, surface,
      and volume do not grow linearly as reported before. We present evidence that
      bacteria grow exponentially during the division cycle, which is consistent with
      previous proposals. Our results confirm previous incorporation studies that
      demonstrate basically exponential growth patterns for cell mass during the
      division cycle.

PMID- 9575235
TI  - Purification and characterization of the tetrachloroethene reductive dehalogenase
      of strain PCE-S.
AB  - The membrane-associated tetrachloroethene reductive dehalogenase from the
      tetrachloroethene-reducing anaerobe, strain PCE-S, was purified 165-fold to
      apparent homogeneity in the presence of the detergent Triton X-100. The purified
      dehalogenase catalyzed the reductive dechlorination of tetrachloroethene to
      trichloroethene and of trichloroethene to cis-1,2-dichloroethene with reduced
      methyl viologen as the electron donor, showing a specific activity of 650 nkat/mg
      protein. The apparent Km values of the enzyme for tetrachloroethene,
      trichloroethene, and methyl viologen were 10 microM, 4 microM, and 0.3 mM,
      respectively. SDS-PAGE revealed a single protein band with an apparent molecular
      mass of 65 kDa. The apparent molecular mass of the native enzyme was 200 kDa as
      determined by gel filtration. Tetrachloroethene dehalogenase contained 0.7 +/-
      0.3 mol corrinoid, 1.0 +/- 0.3 mol cobalt, 7.8 +/- 0.5 mol iron, and 10.3 +/- 2.0
      mol acid-labile sulfur per mol subunit. The pH optimum was approximately 7.2, and
      the temperature optimum was approximately 50 degrees C. The dehalogenase was
      oxygen-sensitive with a half-life of approximately 50 min. The N-terminal amino
      acid sequence of the enzyme was determined, and no significant similarity was
      found to any part of the amino acid sequence of the tetrachloroethene (PCE)
      reductive dehalogenase from Dehalospirillum multivorans.

PMID- 9575236
TI  - Purification and characterization of a catalase from the nonsulfur phototrophic
      bacterium Rhodobacter sphaeroides ATH 2.4.1 and its role in the oxidative stress
      response.
AB  - When challenged with reactive oxidants, the nonsulfur phototrophic bacterium
      Rhodobacter sphaeroides ATH 2.4.1 exhibited an oxidative stress response during
      both phototrophic and chemotrophic growth. Upon preincubation with 100 microM
      H2O2, catalase activity increased fivefold. Catalase was also induced by other
      forms of oxidative stress, heat-shock, ethanol treatment, and stationary-phase
      conditions. Only one band of catalase activity was detected after native and
      denaturing PAGE. The enzyme was purified 304-fold with a yield of 7%. The
      purified enzyme displayed a heterodimeric structure with subunits of 75 and 68
      kDa, corresponding to a molecular mass of approximately 150 kDa for the native
      enzyme. The subunits had almost identical amino-terminal peptide sequences,
      sharing substantial similarity with other bacterial catalases. The enzyme
      exhibited an apparent Km of 40 mM and a Vmax of 285,000 U (mg protein)-1.
      Spectroscopic analysis indicated the presence of protoheme IX. The heme content
      calculated from pyridine hemochrome spectra was 0.43 mol per mol of enzyme. The
      enzyme had a broad pH optimum and was inhibited by cyanide, azide, hydroxylamine,
      2-mercaptoethanol, and sodium dithionite. These data indicate that this catalase
      belongs to the class of monofunctional catalases.

PMID- 9575237
TI  - Phenylacetyl-CoA:acceptor oxidoreductase, a new alpha-oxidizing enzyme that
      produces phenylglyoxylate. Assay, membrane localization, and differential
      production in Thauera aromatica.
AB  - Anaerobic oxidation of phenylalanine and phenylacetate proceeds via alpha
      oxidation of phenylacetyl-CoA to phenylglyoxylate. This four-electron oxidation
      system was studied in the denitrifying bacterium Thauera aromatica. It is
      membrane-bound and was solubilized with Triton X-100. The system used
      dichlorophenolindophenol as an artificial electron acceptor; a spectrophotometric
      assay was developed. No other products besides phenylglyoxylate and coenzyme A
      were observed. The enzyme was quite oxygen-insensitive and was inactivated by low
      concentrations of cyanide. Enzyme activity was induced under denitrifying
      conditions with phenylalanine and phenylacetate, it was low in cells grown with
      phenylglyoxylate, and it was virtually absent in cells grown with benzoate and
      nitrate or after aerobic growth with phenylacetate.

PMID- 9575238
TI  - The two 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase isoenzymes from
      Saccharomyces cerevisiae show different kinetic modes of inhibition.
AB  - Activity of the tyrosine-inhibitable 3-deoxy-d-arabino-heptulosonate-7-phosphate
      synthase (EC 4.1.2.15) from Saccharomyces cerevisiae that was encoded by the ARO4
      gene cloned on a high-copy-number plasmid was enhanced 64-fold as compared to the
      wild-type. The enzyme was purified to apparent homogeneity from the strain that
      harbored this recombinant plasmid. The estimated molecular weight of 42,000 of
      the enzyme corresponded to the calculated molecular mass of 40 kDa deduced from
      the DNA sequence. The enzyme could be inactivated by EDTA in a reaction that was
      reversed by several bivalent metal ions; presumably a metal cofactor is required
      for enzymatic catalysis. The Michaelis constant of the enzyme was 125 microM for
      phosphoenolpyruvate and 500 microM for erythrose 4-phosphate. The rate constant
      was calculated as 6 s-1, and kinetic data indicated a sequential mechanism of the
      enzymatic reaction. Tyrosine was a competitive inhibitor with phosphoenolpyruvate
      as substrate of the enzyme (Ki of 0.9 microM) and a noncompetitive inhibitor with
      erythrose 4-phosphate as substrate. This is in contrast to the ARO3-encoded
      isoenzyme, where phenylalanine is a competitive inhibitor with erythrose 4
      phosphate as a substrate of the enzyme and a noncompetitive inhibitor with
      phosphoenolpyruvate as substrate.

PMID- 9575239
TI  - Acetyl-CoA decarbonylase/synthase complex from Archaeoglobus fulgidus.
AB  - The acetyl-CoA decarbonylase/synthase (ACDS) multienzyme complex catalyzes the
      reversible cleavage and synthesis of acetyl-CoA in methanogens. This report of
      the enzyme complex in Archaeoglobus fulgidus demonstrates the existence of a
      functional ACDS complex in an organism that is not a methanogen. The A. fulgidus
      enzyme complex contained five subunits of 89, 72, 50, 49.5, and 18.5 kDa, and it
      catalyzed the overall synthesis of acetyl-CoA according to the following
      reaction: CO2 + 2 Fdred(Fe2+) + 2 H+ + CH3 - H4SPt + CoA <==> acetyl-CoA + H4SPt
      + 2 Fdox(Fe3+) + H2O where Fd is ferredoxin, and CH3-H4SPt and H4SPt denote N5
      methyl-tetrahydrosarcinapterin and tetrahydrosarcinapterin, respectively.

PMID- 9575240
TI  - A temperature-sensitive DNA adenine methyltransferase mutant of Salmonella
      typhimurium.
AB  - A temperature-sensitive mutant of Salmonella typhimurium was isolated earlier
      after transposon mutagenesis with Tn10d Tet. The mutant D220 grows well at 28
      degreesC but has a lower growth rate and forms filaments at 37 degreesC.
      Transposon-flanking fragments of mutant D220 DNA were cloned and sequenced. The
      transposon was inserted in the dam gene between positions 803 and 804 (assigned
      allele number: dam-231 : : Tn10d Tet) and resulted in a predicted ten-amino-acid
      shorter Dam protein. The insertion created a stop codon that led to a truncated
      Dam protein with a temperature-sensitive phenotype. The insertion dam-231 : :
      Tn10d Tet resulted in a dam "leaky" phenotype since methylated and unmethylated
      adenines in GATC sequences were present. In addition, the dam-231 : : Tn10d Tet
      insertion rendered dam mutants temperature-sensitive for growth depending upon
      the genetic background of the S. typhimurium strain. The wild-type dam gene of S.
      typhimurium exhibited 82% identity with the Escherichia coli dam gene.

PMID- 9575241
TI  - Monoamine oxidase B single-photon emission tomography with [123I]Ro 43-0463:
      imaging in volunteers and patients with temporal lobe epilepsy.
AB  - Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various
      neurological diseases. In the past non-invasive assessment of MAO B has only been
      possible with positron emission tomography (PET) ligands. Given the limited
      availability of PET, a single-photon emission tomography (SPET) ligand would be
      desirable. In this study SPET imaging with the new MAO B inhibitor [123I]Ro 43
      0463 was performed in five volunteers and nine patients with temporal lobe
      epilepsy (TLE). In two volunteers a second study was performed 12 h following
      blockade with deprenyl. In the TLE patients the tracer was administered as bolus
      (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated
      well with the known distribution of MAO B. In the two blocking studies ligand
      uptake was substantially reduced compared with baseline. In the TLE patients
      increased uptake was found in the ipsilateral mesial temporal lobe and,
      surprisingly, in the ipsilateral putamen. This study indicates the potential of
      the new SPET ligand [123I]Ro 43-0463 to map MAO B concentration in the human
      brain. The new finding of increased MAO B in the putamen of TLE patients needs
      further studies to elucidate its exact pathophysiology.

PMID- 9575242
TI  - In vivo evaluation of a lead-labeled monoclonal antibody using the DOTA ligand.
AB  - The aim of this study was to assess the utility of a radioimmunoconjugate
      containing a lead radionuclide for therapy and scintigraphy applications. The
      radioimmunoconjugate evaluated consisted of a bifunctional DOTA ligand and
      monoclonal antibody (MAb) B72.3 using athymic mice bearing LS-174T tumors, human
      colon carcinoma xenografts. In the studies reported here, the lead-203-DOTA
      complex itself was first demonstrated to have in vivo stability. MAb B72.3 was
      then conjugated with the DOTA ligand and labeled with 203Pb, and the
      immunoreactivity of B72.3 was maintained. The localization of the
      radioimmunoconjugate to tumor tissue and other select organs paralleled that of
      DOTA-125I-B72.3, suggesting a similar metabolic pattern of the two
      radioimmunoconjugates. Thus, the DOTA-metal complex does not alter the behavior
      of the radioimmunoconjugate. Tumor localization of the 203Pb-DOTA-B72.3 conjugate
      was demonstrated with biodistribution studies as well as immunoscintigraphy
      studies. Such data highlight the stability of a lead radionuclide in the DOTA
      ligand. The suitability of this chelation chemistry for labeling
      radioimmunoconjugates with a lead radionuclide now makes its application in
      nuclear medicine a feasible proposition.

PMID- 9575243
TI  - Unsulfated DTPA- and DOTA-CCK analogs as specific high-affinity ligands for CCK-B
      receptor-expressing human and rat tissues in vitro and in vivo.
AB  - Receptors for regulatory peptides such as somatostatin or vasoactive intestinal
      polypeptide are expressed by a number of human neoplasms and can be visualized in
      vivo with peptide receptor scintigraphy. Recently, the CCK-B receptor, which
      binds both gastrin and cholecystokinin with high affinity, was shown using in
      vitro methods to be overexpressed in a number of human tumor tissues, including
      medullary thyroid carcinomas, small cell lung cancers, astrocytomas,
      gastrointestinal tumors, and stromal ovarian cancers. In the present study, we
      have designed novel, unsulfated CCK octapeptide analogs linked to the metal
      chelating DTPA and DOTA, and have tested them for their binding affinity to CCK-B
      receptor-positive tissue from human tumors: The most potent compounds assayed
      were DTPA-[Nle28, 31]-CCK(26-33) (MP2286) and DTPA-[d-Asp26,Nle28,31]-CCK(26-33)
      (MP2288) with an IC50 of 1.5 nM. For comparison, analogs with C-terminal DTPA,
      such as [Nle28,31,Aphe33(p-NH-DTPA)]-CCK(26-33) and CCK-(26-33)-NH(CH2)2 NH-DTPA,
      had an IC50 of >100 nM. DOTA-[D-Asp26, Nle28,31]-CCK(26-33) had an IC50 of 3.9
      nM. The compounds were selective for CCK-B receptors as they did not bind with
      high affinity to CCK-A receptors expressed in human tumors (meningiomas or
      gastroenteropancreatic tumors). In vivo rat biodistribution studies with indium
      111 labeled MP2286 and MP2288 showed that the primary mode of clearance was
      renal, and the primary sites of uptake (% ID/g 24 h p.i.) were kidneys (0.270 and
      0.262, respectively) and the gastrointestinal tract. The CCK-B receptor
      expressing gastric mucosa showed specific in vivo accumulation of 111In-labeled
      MP2288 which could be blocked in the presence of excess unlabeled MP2288. 111In
      labeled MP2286 and MP2288 were also found to be stable in human plasma whereas
      both compounds were degraded in urine (>40% after 3 h at 37 degrees C). The
      affinity, specificity, biodistribution, and stability of these two DTPA-CCK
      analogs indicate that these compounds have substantial promise for use in the in
      vivo visualization of CCK-B receptor-expressing tumors.

PMID- 9575244
TI  - Optimization of X-ray mammography and technetium-99m methoxyisobutylisonitrile
      scintimammography in the diagnosis of non-palpable breast lesions.
AB  - The purpose of this study was to evaluate the contribution of technetium-99m
      methoxyisobutylisonitrile (MIBI) scintimammography to the early diagnosis of
      breast cancer in 78 patients with non-palpable breast lesions detected by
      mammography. In all cases biopsy was indicated and they were classified into
      three groups according to the mammographic findings: high (28), intermediate (30)
      and low (20) mammographic probability of malignancy. Histological diagnosis
      confirmed 37 benign and 41 malignant lesions. In the high-probability group 99mTc
      MIBI scintimammography changed the four false-positives into true negatives at
      the expense of two false-negatives; in the intermediate group it changed nine of
      the 17 false-positives into true-negatives at the expense of one false-negative,
      and in the low-probability group it changed five of the 16 false-positives into
      true-negatives without false-negatives. Applying scintimammography to patients
      included in the intermediate and low-probability groups together, 14 of the 33
      mammographic false-positives were changed into true-negatives with 1 false
      negative; thus, 41% of the unnecessary biopsies would have been avoided. When
      MIBI scintimammography was applied to the low-probability group, the negative
      predictive value was 100% and the unnecessary biopsies would have been reduced by
      31%.

PMID- 9575245
TI  - Quantification of iodine-131 in tumors using a threshold based on image contrast.
AB  - Accurate and reproducible quantification of tumor radioactivity by imaging
      requires definition of a region of interest (ROI) for the tumor. The use of a
      threshold for creating the tumor ROI based on tumor-to-background image contrast
      (image contrast) was examined. Quantification of iodine-131 in spheres in a
      phantom that simulated tumors in patients was investigated using planar imaging
      and geometric-mean and effective-point-source methods. Thresholds that provided
      the least quantitative error for spheres with different diameters (1-5 cm) and
      locations (0-11 cm deep in the body), 131I concentrations (0.037-3.2 MBq/ml), and
      sphere-to-background concentration ratios (1:0, 14:1 and 7:1) were investigated.
      The correlation between threshold and sphere image contrast was examined. The
      phantom study showed that an appropriate threshold value for quantification of
      tumor radioactivity could be determined using image contrast for a single view,
      provided that image contrast was >/=1.5. The error of quantification was less
      than 10% for spheres with high image contrast (>/=1.5) but was greater than 17%
      for spheres with low image contrast (<1.5). When image contrast-dependent
      thresholds were applied to patient studies, 131I concentrations determined by
      imaging were in good agreement with the concentrations determined by counting
      biopsy samples. Additionally, reproducibility was improved when compared with a
      visual boundary method. It is concluded that accurate and reproducible
      quantification of radioactivity in tumors is achievable using thresholds based on
      image contrast if image contrast is greater than or equal to 1.5. Optimal
      thresholds for quantification of tumor radioactivity were similar if image
      contrast was similar despite differing tumor diameters, locations and 131I
      concentrations. Under certain circumstances, the effective-point-source method
      was preferable to the geometric-mean method.

PMID- 9575246
TI  - Prognostic relevance of pancreatic uptake of technetium-99m labelled human
      polyclonal immunoglobulins in patients with type 1 diabetes.
AB  - Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction
      of insulin-producing beta cells. Approximately 10%-20% of patients may benefit
      from adjuvant immunotherapy upon diagnosis of the disease in order to protect
      residual beta-cell function. It has been suggested that this subgroup of patients
      differs from others by virtue of the presence of residual pancreatic inflammation
      and beta-cell function. In this study we have investigated to what extent
      technetium-99m-labelled human polyclonal immunoglobulins (99mTc-HIG) accumulate
      in the pancreas of IDDM patients at the time of diagnosis and 1 year thereafter,
      with a view to ascertaining whether HIG scintigraphy is useful for the
      identification of IDDM patients with residual pancreatic inflammation. Patients
      with recent-onset IDDM (n=15) were investigated at the time of diagnosis and 1
      year later, and ten age- and sex-matched normal subjects were also studied. Gamma
      camera imaging and target to background ratio, analysed blind by three
      independent readers, were used to quantify the radioactivity in the pancreatic
      region and findings were correlated with metabolic, immunological and clinical
      parameters. Seven out of 15 newly diagnosed IDDM patients showed a significant
      accumulation of radiolabelled HIG in the pancreas (pancreas/bone ratio higher
      than the mean +2SD of normal subjects). One year after diagnosis, pancreatic
      accumulation of HIG was still detectable in most IDDM patients who were positive
      at the time of diagnosis. Six out of seven patients with positive scintigraphy
      had a partial clinical remission. These results indicate that HIG scintigraphy at
      the time of onset of diabetes identifies a subset of patients with residual beta
      cell function who may benefit from adjuvant immunotherapy.

PMID- 9575247
TI  - Is there any advantage to the acquisition of 24-hour thallium images, in the
      presence of persistent perfusion defects at 4 h after reinjection?
AB  - We determined the incidence of delayed 24-h reversibility post thallium-201
      reinjection and imaging at 4 h, as well as the prognostic and significance of
      such delayed reversibility. We studied 46 consecutive patients with persistent
      thallium-201 perfusion or incompletely reversible single-photon emission
      tomography (SPET) perfusion defects acquired within 10 min after reinjection
      performed 4 h after stress. In 38 of 46 patients (82%) 24-h images showed no
      further reversibility beyond the post-reinjection 4-h study (group A). Eight of
      46 patients (17%) demonstrated reversibility on 24-h imaging (group B). Of these
      eight, three patients showed no improvement compared with the post-stress images,
      with a mean perfusion score of the abnormal segments of 1. 25+/-0.50 on the 4-h
      images, and of 3.00 on the 24-h images, where normal is 4. Four patients
      presented with nine mixed regions. Four of these regions showed an improvement in
      the mean perfusion score of 2.50+/-0.58 on 4- and 24-h images. Two of them, with
      moderate/severe defects, demonstrated complete reversibility at 4-h post
      reinjection imaging. In addition, five other regions presented no improvement at
      4-h imaging, but showed an improvement in the mean perfusion score from 0.80+/
      0.84 at 4-h to 3.30+/-0.89 at 24-h imaging. Two of these regions in one patient
      showed a severe perfusion score of 0 at 4 h, and complete reversibility at 24
      hours, with a mean score improvement of 4. Another patient had three severe
      perfusion defects; two of them redistributed partially at 4 h and completely at
      24 h. The remaining segment with a perfusion score of 0 at 4 h, presented
      complete reversibility with a score of 4 at 24 h. Two (4%) patients revealed
      significant reversibility at 24 h in a region that was severely underperfused
      after post-reinjection imaging at 4 h. Among group B patients, 75% (6/8) had
      recent acute ischemic syndrome, compared with only 13% (5/38) in group A (P = 0.
      001). Among 11 patients with unstable angina, six (55%) had evidence of delayed
      24-h reversibility, compared with 2 of 35 (6%) patients without clinically acute
      ischemia (P = 0.001). On follow-up, there were seven (17%) cardiac deaths among
      the 38 group A patients but three (38%) among the eight group B patients (P =
      0.3). These findings suggest that although the presence of delayed 24-h 201Tl,
      post-reinjection reversibility is infrequent, it has potential clinical
      importance. Thus, delayed 24-h imaging should be considered in the context of
      unstable angina or other acute coronary syndromes.

PMID- 9575248
TI  - Evaluation of global and regional left ventricular function using technetium-99m
      sestamibi ECG-gated single-photon emission tomography.
AB  - We evaluated a method for the assessment of left ventricular (LV) function with
      technetium-99m sestamibi ECG-gated single-photon emission tomography (GSPET).
      GSPET was performed at rest in 21 patients. Images were reconstructed to obtain
      end-diastolic (ED) and end-systolic (ES) images. Endocardial and epicardial edges
      of the left ventricle for the ED and ES images were defined using the gradient
      images and the algorithm developed. LV wall thickness was measured for the mid
      ventricular slices of ED and ES images at 10 degrees intervals. The systolic
      thickening (ST) and the LV ejection fraction [LVEF(GSPECT)] could be determined.
      These values were compared with the LV ejection fraction (LVEF) estimated using
      the gated blood pool method. There was a linear correlation between LVEF and ST
      (r=0.79), and LVEF and LVEF(GSPET) (r=0.87). Histograms of LV thicknesses were
      generated. Agreement for evaluation of regional wall motion between the method
      using histograms of LV thicknesses and the gated blood pool study was 92.8%
      (kappa=0.75). It is concluded that with an appropriate method for LV edge
      detection, GSPET with 99mTc-labelled perfusion agents is of use for simultaneous
      evaluation of myocardial perfusion and assessment of LV function.

PMID- 9575249
TI  - Regional myocardial wall thickening and global ejection fraction in patients with
      low angiographic left ventricular ejection fraction assessed by visual and
      quantitative resting ECG-gated 99mTc-tetrofosmin single-photon emission
      tomography and magnetic resonance imaging.
AB  - We investigated the use of visual and quantitative technetium 99m tetrofosmin ECG
      gated single-photon emission tomography (SPET) for the assessment of regional
      myocardial wall thickening (WT) and left ventricular (LV) ejection fraction (EF)
      in comparison with gated magnetic resonance imaging (MRI) in patients with a low
      angiographic LVEF. Gated SPET using 99mTc-labelled flow tracers offers potential
      for simultaneous assessment of myocardial perfusion and LV function. Few data are
      available on the use of visual and quantitative gated SPET in patients with low
      LVEF. In this study 21 patients with low angiographic LVEF (mean 37%+/-5%) were
      studied. Resting gated 99mTc-tetrofosmin SPET and gated MRI were performed within
      48 h. WT was assessed by visual interpretation (five point score) and
      quantitative analysis based on count increase. There was good agreement for EF
      measurements by MRI and gated SPET (mean EF: 33%+/-12% vs 35%+/-11%, r = 0.86,
      P<0.001). Areas under receiver operator characteristic curves (AUC) for
      differentiation between MRI WT score points ranged from 0.60 to 0.66 for visual
      SPET WT analysis, from 0.59 to 0.71 for delta count increase values and from 0.46
      to 0.60 for % WT, indicating substantial overlap between WT categories. Absolute
      agreement for visual WT between MRI and gated SPET ranged from 25% to 57% (kappa
      0.03-0.25) depending on tracer uptake, and was limited in areas with moderate to
      severe perfusion defects (kappa 0.03-0.13). It is concluded that gated SPET
      provided reliable estimates of regional WT and global function in patients with
      low angiographic LVEF.

PMID- 9575251
TI  - Scintigraphic detection of infection and inflammation: new developments with
      special emphasis on receptor interaction.
AB  - Various conventional radiopharmaceuticals are currently available for
      scintigraphic imaging of infection and inflammation. Although a wide variety of
      infectious and inflammatory foci can be detected with these agents, several
      disadvantages limit their application. These limitations have stimulated the
      search for new radiopharmaceuticals. In the past decade a new class of
      radiopharmaceuticals has emerged: radiolabelled receptor-specific small proteins
      and peptides. These proteins and peptides are naturally occurring inflammatory
      mediators which specifically bind to receptors abundantly present in the area of
      inflammation. In addition, owing to their small size, they rapidly clear from all
      non-target tissues. This paper provides an overview of these newly developed
      agents, focussing on imaging characteristics and in vivo uptake mechanisms.

PMID- 9575250
TI  - Pharmacokinetics and dosimetry of iodine-123 labelled PE2I in humans, a
      radioligand for dopamine transporter imaging.
AB  - The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2-beta
      carbomethoxy-3beta-(4-methylphenyl) nortropane ([123I]PE2I) was evaluated as a
      probe for in vivo dopamine transporter imaging in the human brain. Six healthy
      subjects were imaged with a high-resolution single-photon emission tomography
      scanner. Striatal radioactivity peaked at 1 h after injection. The background
      radioactivity was low. The volume of distribution in the striatum was 94+/-24
      ml/ml. The results were compared with those of [123I]beta-CIT imaging. There was
      no significant uptake of [123I]PE2I in serotonin-rich regions such as the
      midbrain, hypothalamus and anterior gingulus, suggesting that in vivo binding is
      specific for the dopamine transporter. One main polar metabolite of [123I]PE2I
      was found in plasma, and the parent plasma concentration decayed rapidly.
      Radiation exposure to the study subject is 0.022+/-0.004 mSv/MBq (effective
      dose). The preliminary results suggest that [123I]PE2I is a selective SPET ligand
      for imaging striatal dopamine transporter density.

PMID- 9575252
TI  - The epidemiology of sports-related traumatic brain injuries in the United States:
      recent developments.
AB  - We examined recent population-based data from the National Health Interview
      Survey, Consumer Product Safety Commission, and state-based traumatic brain
      injury (TBI) surveillance programs that provide estimates of the overall
      incidence of sports-related TBI in the United States. Available data indicate
      that sports-related TBI is an important public health problem because of the
      large number of people who incur these injuries each year (approximately
      300,000), the generally young age of patients at the time of injury (with
      possible long-term disability), and the potential cumulative effects of repeated
      injuries. The importance of this problem indicates the need for more effective
      prevention measures. The public health approach can guide efforts in injury
      prevention and control. The steps in this approach are (1) identifying the
      problem, (2) identifying risk factors, (3) developing and testing interventions,
      and (4) implementing programs and evaluating outcomes. Each of these steps
      requires adequate data. This article examines the limitations of current sports
      related TBI data and suggests ways to improve data in order to develop more
      effective injury prevention strategies. The impact of sports-related TBI on the
      public indicates that this task deserves a high priority.

PMID- 9575253
TI  - Neuropsychological assessment of the college football player.
AB  - The application of neuropsychological assessment procedures to the evaluation of
      athletes has recently become an area of intense interest and debate and has led
      to the development of research initiatives at both the amateur and the
      professional level. However, to date, only a handful of research studies have
      been completed that have addressed the special issues that accompany the use of
      neuropsychological assessment instruments with athletes. This article reviews the
      past use of psychological testing in sports and presents a model of
      neuropsychological assessment that is currently being utilized in the National
      Football League. In addition, the extension of this approach to major college
      football is discussed and test-retest data from a sample presented to provide the
      basis for comparison of athletes who have suffered a concussion. Recommendations
      of a national panel of neuropsychologists who are involved in the evaluation of
      athletes are presented in hopes of encouraging new research initiatives in this
      area.

PMID- 9575254
TI  - Standardized assessment of concussion (SAC): on-site mental status evaluation of
      the athlete.
AB  - OBJECTIVE: This study investigated the clinical utility of the Standardized
      Assessment of Concussion (SAC) in detecting concussion in athletes. METHOD:
      Athletic trainers administered the SAC to 568 nonconcussed high school and
      college football players prior to the 1995 and 1996 football seasons. Thirty
      three of these players experienced concussion and were tested immediately
      following injury; 28 of the 33 underwent additional follow-up testing 48 hours
      after the injury. RESULTS: Concussed players scored significantly below
      nonconcussed controls on all SAC measures and significantly below their own pre
      injury baseline performance. Follow-up testing documented return to preinjury
      baseline. CONCLUSION: These findings support the SAC's effectiveness in detecting
      concussion and tracking recovery in order to determine a player's fitness to
      return to play.

PMID- 9575255
TI  - Future directions for the neuropsychological assessment of sports concussion.
AB  - This article argues in favor of using newly developed computerized, complex
      reaction time (RT)-based neuropsychological procedures for the study of sports
      related concussion. Recent studies show that by using these complex RT
      procedures, significant differences between concussed and control samples can be
      observed. The magnitude of RT differences is 110 ms or less, levels that are not
      meaningfully measured with stopwatch-based procedures. RT-based procedures also
      have the advantage of permitting analysis of variability of RT, and several
      recent studies have shown that brain dysfunction is accompanied by erratic and
      inconsistent RT. A currently ongoing sports concussion study using measures of
      complex RT and variability of RT is described.

PMID- 9575256
TI  - Is heading a soccer ball injurious to brain function?
AB  - With the growing popularity of soccer both in the United States and worldwide,
      reports of adverse effects of 'heading' on brain function are a source of
      concern. This article reviews the related research literature on neurologic and
      neuropsychological findings. Neurologic and neuropsychological abnormalities have
      been reported in a significant minority of older former professional players in
      Norway. Purportedly unrelated to age, the most prominent findings were cerebral
      atrophy and impairment on intelligence test abilities that are particularly
      vulnerable to brain damage. Also noteworthy in these retired players were
      persistent physical, cognitive, and emotional complaints consistent with a
      postconcussive syndrome. Younger amateur players appear to be free of major
      abnormalities, although some report persistent difficulties with memory and
      concentration. The severity of these complaints may be related to a history of
      soccer-related head injuries and not necessarily specific to heading. Research
      findings specific to heading are not more than suggestive at best, and
      clarification of the risks of heading a soccer ball awaits more definitive
      studies.

PMID- 9575258
TI  - TBI state demonstration grants.
AB  - In 1996, the Congress enacted Public Law 104-166, known as the Traumatic Brain
      Injury (TBI) Act, "to provide for the conduct of expanded studies and the
      establishment of innovative programs with respect to traumatic brain injury."1 As
      part of this Act, the Health Resources and Services Administration (HRSA)
      Maternal and Child Health Bureau (MCHB) is responsible for implementing the TBI
      State Demonstration Program and issuing demonstration grants to improve health
      and other services regarding persons with TBI and their families.

PMID- 9575257
TI  - The development of guidelines for the management of concussion in sports.
AB  - Concussion in sports has caught the attention of the news media in recent years,
      primarily due to the high profile of certain athletes who have sustained
      traumatic brain injuries. Even though the management of concussion remains
      somewhat controversial, certain principles of neuroscience regarding mental
      status alterations and other symptoms resulting from concussion are well accepted
      by medical experts. Several authors have previously published management
      strategies for sports-related concussion based on their own experiences, but this
      article will describe the formal process of developing guidelines for the
      diagnosis and management of concussion in sports. The processes of literature
      review, evidence-based analysis, and consensus building are described. This
      article includes the grading scale, sideline evaluation, and management strategy
      adopted as a practice parameter by the American Academy of Neurology. Emphasis is
      placed on the need to detect mild forms of concussion through detailed
      observation and examination of athletes.

PMID- 9575259
TI  - The politics of FDA reform.

PMID- 9575260
TI  - Internet resources in traumatic brain injury: getting started.

PMID- 9575261
TI  - Enthusiasm in rehabilitation in the era of managed care.

PMID- 9575262
TI  - Ethical and quasi-ethical issues in medical editing and publishing.
AB  - The peer review system is a complex, delicately balanced, and dynamic system by
      which most new medical information is made known. The participants in the process
      - authors, reviewers, and editors - all have responsibilities to shoulder and
      rights that need to be protected. An ethical structure has evolved over time to
      accomplish these two goals. This paper discusses six of these ethical or quasi
      ethical issues. Authorship is currently a contentious matter, in part because
      authors see it as a credit, whereas editors view it as responsibility. Conflict
      of interest, usually financial, which seems to be increasing with the growing
      commercialization of medicine, can undermine the credibility and integrity of
      publication. Confidentiality is an essential component of peer review to protect
      an author's creative work from exploitation or misappropriation and to protect
      reviewers from retribution. Redundant publication, publishing or attempting to
      publish essentially the same work more than once, is regarded seriously because
      it wastes a journal's resources, confuses later literature reviews, and
      depreciates the value of authorship. Advertising is a necessary fact of life for
      most medical journals, but safeguards must be in place to prevent its influencing
      editorial decisions. When fraud or plagiarism is alleged about something a
      journal has published, the journal is not equipped to undertake the kind of
      investigation needed, and should refer the matter to the institution that
      sponsored the research.

PMID- 9575263
TI  - Should all pregnant women have an ultrasound examination?
AB  - This paper addresses the question whether all pregnant women should have an
      ultrasound examination. We used the methods of ethical analysis and argument to
      show that the principle of respect for autonomy creates an obligation to inform
      every pregnant woman about the availability of obstetric ultrasound in settings
      in which quality ultrasound is available. We considered two objections to this
      position, lack of benefit and excessive costs, and showed that these objections
      did not succeed. Obstetricians throughout the world should be advocates for
      informing pregnant women about the availability of routine obstetric ultrasound.

PMID- 9575264
TI  - Transient patterns of organization of the human fetal brain.
AB  - Fetal development of the human brain is characterized by continuous
      transformations and reorganization of the fetal telencephalic wall which consists
      of transient, cytoarchitectonically defined cellular compartments, the so-called
      embryonic/fetal zones. The cellular and fiber content of these zones is
      permanently changing, so that fetal neuronal circuitry elements (afferent fibers,
      synapses, and postsynaptic neurons) display transient patterns of areal, laminar,
      and modular organization. In the late human fetus and preterm infant, transient
      patterns of structural and physiological organization form the basis of transient
      behavioral states and patterns of activity. The transient subplate zone is a key
      compartment for transient fetal neuronal circuitry, and competitive cellular
      interactions within the subplate zone are crucial for the areal specification of
      the cerebral cortex and the formation of cortical connectivity. The subplate zone
      may also have a key role in cortical repair and plasticity after perinatal brain
      lesions.

PMID- 9575265
TI  - Prenatal diagnosis using fetal cells enriched from maternal blood.
AB  - The ability to use fetal cells enriched from the blood of pregnant women for
      prenatal diagnosis has been a long-sought goal for those pursuing a non-invasive
      alternative to current methods, such as amniocentesis or chorionic villus
      sampling. Several new developments, which rely either on fluorescence in situ
      hybridization or the combination of single-cell manipulation and subsequent
      polymerase chain reaction practices, which are common to the field of
      preimplantation genetics, have been tested. We discuss the significance of these
      developments and the obstacles that still have to be surmounted before this
      technology becomes available in a broad diagnostic use. The research in the field
      yielded important observations regarding the traffic of cells between the fetus
      and the mother, which may provide a new insight into the development of disorders
      such as preeclampsia and the associated HELLP (hemolysis, elevated liver enzymes,
      low platelets) syndrome.

PMID- 9575266
TI  - Chromosome analysis of human preimplantation embryos.
AB  - Although karyotyping is the ideal method for diagnosing chromosome anomalies in
      the human embryo, the detection of chromosome anomalies in preimplantation human
      embryos by classical cytogenetics is extremely difficult. Nowadays, fluorescent
      in situ hybridization (FISH) in interphase nuclei is the method of choice. Both
      karyotype studies and FISH analysis of human preimplantation embryos obtained
      after in vitro fertilization (IVF) treatment revealed a high rate (25-51%) of
      chromosomally abnormal embryos. FISH analysis showed that chromosome mosaicism
      (22-24%) and chaotic embryos (7-26%) were the most frequent chromosome anomalies.
      Therefore, it seems that natural selection may be the reason for the low
      implantation rates of human preimplantation embryos in IVF programs. Although it
      is not possible to carry out such studies on embryos from natural conceptions,
      frequent occurrence of chromosome mosaicism and chaotically dividing embryos may
      apply to in vivo conception and explain the low fecundity rates in humans.

PMID- 9575267
TI  - Advances in the imaging of the embryonic brain.
AB  - AIM: Description of the development of the human embryonic brain visualized by
      transvaginal ultrasound. Methods. In two studies, healthy pregnant women without
      any pregnancy complications and normal outcomes were examined by transvaginal
      ultrasound in the early pregnancy between seven and twelve weeks of gestation.
      The hypoechogenic brain cavities were described and measured. RESULTS: Initially,
      the rhombencephalic cavity was the largest brain cavity. It did not increase its
      size significantly during the first trimester. The mesencephalic cavity was
      rather large throughout the first trimester. The dimension of the future third
      ventricle decreased gradually. The hemispheres were the smallest cavities at the
      beginning of week seven. They grew fast and dominated the appearance of the
      embryonic brain from the week nine onwards. CONCLUSION: Size and shape of the
      brain structures showed fast changes during the observation period. The
      ultrasound description of the brain development corresponded to that of classical
      embryology.

PMID- 9575268
TI  - Magnetic resonance of the neonatal brain.
AB  - We discuss the advantages of magnetic resonance (MR) technique in the study of
      the neonatal brain. Major results have been obtained concerning the understanding
      of the normal appearance of the developing brain. Bands of cells migrating to the
      cortex have been identified in the frontal periventricular white matter up to
      late gestation. MR can also identify the disappearance of the subependymal
      germinal matrix with increasing gestational age. With respect to the lesions of
      prematurity, subependymal germinal matrix hemorrhages were for the first time
      identified by MR underneath the posterior horns of the lateral ventricles. Subtle
      ischemic lesions of the periventricular white matter, not detected by brain
      ultrasound scan, are also described. Analysis of the lesions of the term neonates
      showed the role of MR in defining a more precise prognosis of infants who have
      sustained "birth asphyxia". The lesions can affect the basal ganglia, watershed
      areas of the white matter, and cortex. MR scans performed in the second week of
      life seem to show a stronger association with the outcome. Brain ischemic areas
      of the term neonates presenting with focal or multifocal seizures can also be
      detected by MR. These infarcted zones are usually located in the perfusion
      territory of the middle cerebral artery, more often in the left hemisphere. The
      timing of the scan is an important factor as the conventional MR can be negative
      in the first two-three days after the seizures. The diffusion-weighted imaging
      (DWI) is a new MR technique very sensitive to acute ischemic injury, and it may
      solve the problem of the scan timing.

PMID- 9575269
TI  - Clinical neurology in neonatal units.
AB  - Clinical assessment is often neglected in neonatal intensive care units due to
      technical difficulties. When a child is in a more stable situation and when
      maturation progresses with postnatal weeks, neurologic assessment becomes more
      and more important, as it is related to the upper hemispheric functions. Several
      aspects are discussed here: 1) identification of maturation stages measured at 2
      week intervals; 2) assessment of optimal central nervous system function in
      fullterm neonates at 40 corrected weeks; and 3) identification of neurologic
      signs and symptoms, evolutive profile, and estimation of severity. Early
      intervention programs and follow-up have to be based on these clinical findings
      in order to focus on the infants who really need these services.

PMID- 9575271
TI  - Contemporary treatment options for meconium aspiration syndrome.
AB  - The presence of meconium in the respiratory tract causes atelectasis, hypoxemia,
      hypercapnia, persistent pulmonary hypertension, inflammatory changes, and
      surfactant inactivation. Prevention is the most important factor in the
      management of meconium aspiration syndrome and it includes both prenatal and
      postnatal care. Prenatal procedures include constant fetal heart rate monitoring
      during labor, examination of acid-base equilibrium in the capillary blood from
      the fetal scalp, and eventually amnioinfusion. Amnioinfusion is not a widely
      accepted care and further studies to confirm its benefits are required. Postnatal
      procedures include obligatory suction of the oral-pharyngeal cavity and nose
      before the first breath, and selective endotracheal suction only in depressed
      neonates or neonates born from thick meconium-stained amniotic fluid.
      Conventional therapy of meconium aspiration syndrome includes monitoring of vital
      functions, chest physiotherapy, site drainage, airway suction, oxygen supply,
      respiratory support, antibiotics, sedation, normal fluid balance and calories
      intake, and when indicated, agents stabilizing blood pressure and heart rate. New
      management methods of meconium aspiration syndrome, not recommended as standard
      procedures at present include high-frequency oscillatory or jet ventilation as a
      lifesaving therapy, the use of exogenous surfactant, surfactant lavage of the
      bronchial tree, liquid ventilation, and inhalation of nitric oxide.
      Extracorporeal membrane oxygenation is of considerable importance in the
      treatment of the most severe meconium aspiration syndrome, but its role is
      diminishing with the development of other therapeutic methods.

PMID- 9575270
TI  - Transvaginal sonography of the fetal brain: detection of abnormal morphology and
      circulation.
AB  - AIM: To analyze the incidence, transvaginal detection age, sonographic
      appearance, clinical course, and outcomes of pregnancy in cases with abnormal
      fetal brain structure and/or circulation, and to evaluate the clinical
      significance of sonographic abnormalities. METHODS: Serial observation of the
      fetal brain and intracranial Doppler assessment by transvaginal approach at four
      week intervals were performed in 306 singleton fetuses from the first trimester
      and 13 referral cases at our ultrasound units from January 1996 to December 1997.
      Detection of abnormalities was followed by subsequent serial scans every one or
      two weeks. RESULTS: Morphological abnormalities were found in 66 cases: open
      neural tube defect (9 cases), disorders of prosencephalic development (2),
      ventriculomegaly with cerebellar hypoplasia (1), hydrocephalus (1),
      craniosynostosis (1), unclassified brain anomaly (1), brain atrophy (1), isolated
      choroid plexus cysts (19), choroid plexus cysts with cerebellar hypoplasia (2),
      lateral ventricular asymmetry (26), and subependymal cyst (3). Chromosomal
      aberration was found in 4 cases. Artificial abortion was performed in 10 cases
      and fetal demise occurred in 2 cases. Isolated choroid plexus cysts, isolated
      ventricular asymmetry and subependymal cyst were not clinically significant. Two
      abnormal flow patterns of superior sagittal sinus, sharp doubled pulsatile
      pattern, and disappearance of normal pulsatile pattern were found in different
      situations. CONCLUSION: Serial transvaginal observation of the fetal brain
      provided evidence of hitherto unreported intracranial abnormalities: subependymal
      cyst, craniosynostosis, medullary kink in Chiari malformation, brain damage, and
      abnormal venous flows. Venous flow assessment may be of great potential in
      predicting fetal neurological well-being.

PMID- 9575272
TI  - Which interventions for neonatal respiratory failure are effective?
AB  - AIM: To review the evidence from clinical trials of various interventions to
      treat and prevent respiratory failure in the neonate and to determine which
      interventions are effective and which require further study. METHODS: Randomized
      controlled trials and/or meta-analyses of trials of interventions for neonatal
      respiratory failure were sought from databases including the Cochrane
      Collaboration. The results were synthesized as typical relative risks and typical
      risk differences, with 95% confidence intervals (CI). RESULTS: The following
      interventions were effective: conventional mechanical ventilation (absolute
      reduction in mortality 12%, 95% CI 4-21%), continuous positive airway pressure
      (absolute reduction in mortality 15%, 95% CI 1-28%), surfactant therapy (absolute
      reduction in mortality 4 to 9%, 95% CI 1-13%), and extracorporeal membrane
      oxygenation (absolute reduction in mortality 29%; 95% CI 15-42%). High frequency
      oscillatory ventilation with a volume recruitment strategy and inhaled nitric
      oxide appeared promising, but have not yet reduced mortality. Prenatal
      corticosteroids (absolute reduction in mortality 4%; 95% CI 2-6%) and
      amnioinfusion (effect on mortality not yet possible to estimate) prevented
      respiratory failure, but routine endotracheal intubation and suctioning of the
      airways at birth in vigorous meconium-stained term babies did not prove
      effective. CONCLUSIONS: Assisted ventilation, surfactant therapy, and extra
      corporeal membrane oxygenation are effective, but it is uncertain how each should
      be applied in an individual infant. More research is needed to evaluate
      combinations of effective interventions, and effectiveness of high frequency
      oscillation and inhaled nitric oxide. Routine intubation and suctioning of the
      airways at birth in meconium-stained vigorous neonates is not recommended.

PMID- 9575273
TI  - Cummulative pregnancy and live birth rates after assisted conception.
AB  - Within the last 15 years in vitro fertilization (IVF) has become an established
      treatment modality. Its results compare favorably with that of spontaneous
      conception in the natural menstrual cycle in fertile women. The possibility of a
      success for any couple undergoing treatment will, however, depend on their
      characteristics. Over the past several years, the importance of these individual
      factors has been subjected to an extensive research. Our group has performed a
      number of studies that relate the cumulative conception rate (CCR) and cumulative
      live birth rate (CLR) with the age of the patient, the cause of infertility, and
      the type of ovarian stimulation used. We have also analyzed the effect of
      previously successful in vitro fertilization treatment upon the results of a
      subsequent treatment course, and the obstetric outcome of in vitro fertilization
      pregnancies when compared to those that are naturally conceived. In this review
      article, the importance of the above mentioned factors will be discussed in view
      of our research results and other recently available evidence.

PMID- 9575274
TI  - Correlation of serum estrogen levels with uterine and carotid arteries flow in
      postmenopausal women on hormone replacement therapy.
AB  - OBJECTIVE: To determine the pattern of blood flow in the patients compliant and
      non-compliant to hormone replacement therapy. METHODS: In the period of 12
      months, 106 postmenopausal women were examined by the color and pulsed Doppler
      ultrasonography of the blood flow through uterine, common, and internal carotid
      arteries (Resistance Index, RI). The study was retrospective-descriptive.
      Patients were divided into three groups: (1) 38 patients compliant with hormone
      replacement therapy and daily using Premarin/Provera, (2) 27 patients non
      compliant with the treatment because of discontinuation of the therapy and/or
      irregular use of medicine, and (3) control group of 41 women who never used
      hormone replacement therapy. Results were compared with serum estrogen (E2) drawn
      on the day of the blood flow assessment. RESULTS: Mean E2 serum concentration in
      the hormone replacement therapy-compliant group was 90.1 pg/mL, 45.5 pg/mL in the
      non-compliant group, and 26.6 pg/mL in the control group (p<0.01). Serum E2
      concentration correlated with the decrease in resistance to blood flow in the
      uterine artery (p=0.001), but did not in the common carotid (p=0.34) and internal
      carotid arteries (p=0.66). The compliant group and control group differed in the
      uterine artery blood flow (RI 0.78 vs. 0.87, respectively). CONCLUSION:
      Differences in E2 serum concentration between the groups are related to the
      hormone replacement therapy and the patients' compliance to the therapy. Small
      peripheral arteries readily respond to the serum E2 levels, whereas large
      peripheral arteries (common and internal carotid) are too "rigid" to respond to
      E2-induced vasodilatation.

PMID- 9575275
TI  - Diagnosis and treatment outcome of the septate uterus.
AB  - AIM: To compare the accuracy of transvaginal ultrasound, transvaginal color
      Doppler, hysterosonography, and three-dimensional ultrasound in the detection of
      septate uteri. To evaluate obstetrical prognosis of the septate uterus and to
      assess the reproductive outcome following operative hysteroscopy. PATIENTS AND
      METHODS: Four hundred and twenty infertile patients undergoing hysteroscopy were
      evaluated prospectively during a 4 year period. Transvaginal ultrasound and color
      Doppler were performed in all patients, whereas hysterosonography and three
      dimensional ultrasound were used in 76 and 86 patients, respectively. RESULTS:
      The sensitivity of transvaginal ultrasound and transvaginal color Doppler in the
      identification of the septate uterus was 95.0% and 99.3%, respectively. Color and
      pulsed Doppler studies of the septal area revealed vascularity in 71.2%. The
      sensitivity of hysterosonography and three-dimensional ultrasound in the
      detection of the septate uterus were 100% and 93.6%, respectively. However, the
      latter method predicted the existence of a congenital uterine defect in all the
      patients with septate uterus, but was inaccurate in differentiating it from other
      fusion anomalies. The pregnancy rate in 116 patients following the operative
      hysteroscopy for an intrauterine septum in a prospective follow-up period of 24
      months was 50.9%: 44 patients (74.6%) had term deliveries, 11 (18.6%) had first
      trimester abortion, and 4 (6.8%) had preterm delivery. CONCLUSIONS: Transvaginal
      color Doppler and hysterosonography are highly accurate diagnostic tools for
      preoperative evaluation of the uterine cavitary defects. Three-dimensional
      ultrasound increases the accuracy of conventional two-dimensional transvaginal
      scan, allowing precise reconstruction of the uterine cavity. Removing the
      intrauterine septum in patients suffering from infertility and recurrent
      pregnancy wastage is beneficial.

PMID- 9575276
TI  - Sonographic assessment of chorionicity and amnionicity in twin pregnancies: how,
      when and why?
AB  - During the first trimester, chorionicity can be assessed as early as five weeks
      post-conception, but a reliable detection of amnionicity cannot be performed
      before the 8th week when the amnion can be clearly imaged. The late second and
      third trimesters twin pregnancies are a true challenge to the imaging specialist
      because the detection of chorionicity and amnionicity has to rely upon
      sonographic clues, such as placenta location, fetal gender, membrane origin,
      thickness, and layer. Sonographic methods used to determine chorionicity and
      amnionicity in twins can be extrapolated to any multifetal pregnancy, regardless
      of the number of fetuses present.

PMID- 9575277
TI  - How to lower perinatal mortality? Perinatal care in Japan.
AB  - OBJECTIVE: To review the 30-year history of perinatal medical care in Japan, and
      the recently initiated regionalization system of perinatal centers, new
      technologies and treatments in obstetric and neonatal medicine developed in
      Japan. STATISTICAL DATA: Maternal and neonatal health statistics of Japan
      released by the Ministry of Health and Welfare, Japanese Society of Obstetrics
      and Gynecology, Japanese Pediatric Society, and Tokyo Women's Medical University.
      LABORATORY DATA: Serological assay and immunohistochemical staining employing TKH
      2 antibody for the diagnosis of amniotic fluid embolism, and assaying granulocyte
      elastase as a specific inflammatory marker in mucous samples from the uterine
      cervical canal for the prediction of preterm labor or premature rupture of
      membranes. TREATMENTS: Urinary trypsin inhibitor (Urinastatin) for the prevention
      of preterm delivery, and a double-blind, placebo-controlled, randomized trial of
      antithrombin-III therapy in severe preeclampsia. CONCLUSION: Over the last 30
      years, the statistical data of perinatal health care, such as maternal and
      perinatal mortality rates, have markedly improved in Japan. These results are
      supported by the advanced technologies and newly developed treatments in
      obstetric and neonatal medicine. The regionalization of perinatal centers, a
      national project in order to assure a systematic collaboration among primary,
      secondary, and tertiary centers, has just started in Japan. It also aims at
      systematization of the function of perinatal centers on the national level
      through the informative promoting action.

PMID- 9575278
TI  - Assisted reproduction technology, multiple births, and adverse perinatal outcome.
AB  - The increase in the rate of multiple pregnancies in Australia in recent years is
      primarily due to the use of assisted reproduction technology. Compared to
      singleton births, fetal, neonatal, and perinatal mortality rates are 3-6 times
      higher in twins and 5-15 times higher in multiple births of a higher order.
      Cerebral palsy rates among survivors are six times higher in twins and twenty
      times higher in triplets. The increased risks in multiple pregnancies are not
      entirely explained by their higher prematurity and low birthweight rates. In
      Australia, the practice of transferring more than three embryos in any one
      assisted reproduction technology cycle has declined in recent years and, as a
      result, the number of multiple pregnancies from assisted reproduction technology
      has also declined. Nevertheless, assisted reproduction technology pregnancies
      remain to have poorer than normal outcome with regards to spontaneous abortion,
      ectopic pregnancy, preterm birth, low birthweight, and perinatal mortality.
      Infants born after assisted reproduction technology have a higher neonatal
      morbidity rate, including a greater requirement for assisted ventilation, and a
      higher long-term neurodevelopmental disability rate. These adverse outcomes
      following assisted reproduction technology are partly due to the increased risk
      of multiple pregnancy and partly due to preterm and low birthweight. This fact
      and the lack of evidence that the transfer of more than two embryos improves
      pregnancy rates, make it advisable to limit the number of embryos transferred to
      no more than one or two per cycle.

PMID- 9575279
TI  - Partial trisomy 13 in an infant with a mild phenotype: application of
      fluorescence in situ hybridization in cytogenetic syndromes.
AB  - We report on a month-old infant with dysmorphic face and several anomalies known
      to be associated with trisomy 13. Fluorescence in situ hybridization (FISH)
      studies performed on metaphase cells allowed us to identify an extra material on
      the short arm of the chromosome 13 as a duplication of 13q22-qter.

PMID- 9575280
TI  - Transvaginal color doppler ultrasound in the conservative treatment and
      surveillance of three ectopic pregnancies.
AB  - We evaluated the role of transvaginal color Doppler ultrasound in the treatment
      and follow-up after transvaginal instillation of methotrexate in ectopic
      pregnancy. Three patients diagnosed with ectopic pregnancies were treated with a
      single 50 mg dose of methotrexate, transvaginally instilled, under direct color
      sonographic guidance. Inclusion criteria required a gestational age of less than
      8 weeks, non-ruptured ectopic pregnancy, gestational sac of less than 4 cm, and
      compliant patient. b-hCG titers, gestational sac sizes, and Doppler flow waveform
      analyses were followed at regular intervals. All three patients had falling b-hCG
      titers, shrinkage of the gestational sacs, and normalization of Doppler flow
      waveform indices. Transvaginal color Doppler ultrasound appears to be an
      effective adjunct in the treatment and follow-up of ectopic pregnancies treated
      with transvaginal instillation of methotrexate.

PMID- 9575281
TI  - In utero stem cell transplantation.
AB  - AIM: To investigate feasibility, safety, and efficacy of in utero transplantation
      of hemopoietic stem cells. METHODS: A 10-week fetus was found to have b
      thalassemia major after prenatal diagnosis by chorionic villus sampling and DNA
      analysis. The couple asked for prenatal treatment and, after extensive genetic
      counseling and local Ethical Committee approval, CD34+ hematopoietic progenitor
      cells purified from paternal bone marrow were injected to the fetus
      intraperitoneally, under ultrasound guidance. RESULTS: A healthy 3.5 kg fetus was
      spontaneously delivered with no clinical or laboratory signs of graft-versus-host
      disease. Analysis of the cord blood by high-pressure liquid chromatography
      revealed the absence of adult HbA, typical of b-thalassemic patients. Analysis of
      the Hb chain synthesis showed no clear signs of b-chain presence. CONCLUSIONS: In
      utero transplantation of hematopoietic progenitor cells was not successful for b
      thalassemia. Caution should be taken when considering other applications than
      immunodeficiency diseases.

PMID- 9575283
TI  - Pore mutations alter closing and opening kinetics in Shaker K+ channels.
AB  - 1. We have studied the effects of mutations of amino acids in the pore (positions
      447 and 449) and the elevation of extracellular [K+] on the closing and opening
      kinetics of Shaker B K+ channels transiently expressed in Chinese hamster ovary
      (CHO) cells. 2. Mutant D447E had closing and C-type inactivation kinetics which
      were faster than the wild-type channel. These processes were slowed by increasing
      extracellular [K+] and in these conditions the channels exhibited linear
      instantaneous current-voltage relationships. Thus, the mutation seems to produce
      uniform decrease of occupancy by K+ in sites along the channel pore where the
      cation competes with closing and C-type inactivation. 3. In other mutants also
      showing K+-dependent fast C-type inactivation, closing was found to be slower
      than in the wild-type channel and insensitive to variations in external [K+].
      These characteristics were particularly apparent in mutant T449K which even in
      high [K+] has a non-linear instantaneous current-voltage relationship with marked
      saturation of the inward current recorded at negative membrane potentials. Hence,
      in this channel type occupation by K+ of the pore appears to be non-uniform with
      low occupancy of sites near the outer entrance and saturation of the sites
      accessible from the internal solution. 4. The results show that channel closing
      is influenced by changes in the pore structure leading to alterations in the
      occupation of the channels by permeant cations. The differential effects of pore
      mutations and high external [K+] on closing and C-type inactivation indicate that
      the respective gates are associated with separate domains of the molecule. 5.
      Point mutations in the pore sequence can also lead to modifications in channel
      opening. In general, channels with fast C-type inactivation also show a fast
      rising phase of activation. However, these effects appear not to be due to
      primary modifications of the activation process but to arise from the coupling of
      activation and C-type inactivation. 6. These data, demonstrating that the pore
      structure influences most of the gating parameters of K+ channels, give further
      insight into the mechanisms underlying the modulation of K+ channel function by
      changes in the ionic composition in the extracellular milieu.

PMID- 9575282
TI  - Hypoxia and smooth muscle function: key regulatory events during metabolic
      stress.
AB  - Hypoxia rapidly reduces force in many smooth muscles and we review recent data
      that shed light on the mechanisms involved. As many regulated cellular processes
      are integrated to co-ordinate smooth muscle contractility, the processes
      responsible for decreased force output with altered metabolism are also likely to
      be many, acting in concert, rather than the actions of one altered parameter.
      Nevertheless the aim of this study is to elucidate the hierarchical series of
      events that contribute to reduced smooth muscle force production during altered
      metabolism. We conclude that in many phasic smooth muscles the decrease in force
      can be attributed to impaired electro-mechanical coupling whereby the Ca2+
      transient is reduced. A direct effect of hypoxia on the Ca2+ channel may be of
      key importance. In tonic vascular smooth muscles KATP channels may also play a
      role in the integrated functional responses to hypoxia. There are also many
      examples of force being reduced, in tonically activated preparations, without a
      fall in steady-state Ca2+; indeed it usually increases. We examine the roles of
      altered [ATP], pH, myosin phosphorylation, inorganic phosphate and proteolytic
      activity on the [Ca2+]-force relationship during hypoxia. We find no defining
      force-inhibitory role for any one factor acting alone, and suggest that force
      most probably falls as a result of the combination of myriad factors.

PMID- 9575284
TI  - KATP channel formation by the sulphonylurea receptors SUR1 with Kir6.2 subunits
      in rat dorsal vagal neurons in situ.
AB  - 1. Functional and molecular properties of ATP-sensitive K+ (KATP) channels were
      studied in dorsal vagal neurons (DVNs) of rat brainstem slices using patch-clamp
      and single-cell antisense RNA amplification-polymerase chain reaction (PCR)
      techniques. 2. In the cell-attached configuration, 1 mM cyanide resulted in block
      of spontaneous firing and concomitant opening of single channels with a mean
      single open time of 2-3 ms and a burst duration of up to several hundred
      milliseconds. Inhibition of such single-channel activity with 200 microM
      tolbutamide led to the reappearance of spontaneous discharge. 3. Whole-cell
      recordings during anoxia revealed a hyperpolarization of the DVNs. Harvesting of
      cytoplasm, antisense RNA amplification and subsequent PCR showed coexpression for
      single DVNs of mRNA for the sulphonylurea receptor SUR1 isoform and for the
      inwardly rectifying K+ channel subunit Kir6.2, but not for the SUR2 or Kir6.1
      isoforms of these channel/receptor subclasses. 4. Upon anoxia, a stable
      depolarization by less than 10 mV was observed in non-excitable cells in the
      dorsal vagal nucleus. These cells, which expressed glial fibrillary acidic
      protein (GFAP), showed a high level of mRNA for Kir6.2, a weak signal for SUR1,
      whereas SUR2 or Kir6.1 were not detected. 5. The results suggest that functional
      KATP channels in DVNs are constituted by the formation of Kir6.2 subunits with
      SUR1 receptors.

PMID- 9575285
TI  - Metabotropic glutamate group II receptors activate a G protein-coupled inwardly
      rectifying K+ current in neurones of the rat cerebellum.
AB  - 1. The effects of the group II metabotropic glutamate receptor (mGluR) agonists
      DCG-IV and LY354740 were examined in neurones freshly dissociated from the rat
      cerebellum and olfactory bulb, using the whole-cell configuration of the patch
      clamp technique. 2. Under experimental conditions in which K+ currents would be
      inward, rapid application of DCG-IV and LY354740 to interneurones expressing the
      group II mGluRs induced an inward current in a subpopulation of interneurones of
      the cerebellum, the unipolar brush cells. 3. The currents induced by DCG-IV and
      LY354740 had the major characteristics of a G protein-coupled inwardly rectifying
      K+ channel (GIRK) current; namely, rapid activation and deactivation upon agonist
      application and removal, G protein dependence, strong inward rectification, Cs+
      and Ba2+ sensitivity, and K+ selectivity. 4. In Golgi cells of the cerebellum and
      interneurones of the accessory olfactory bulb, which also express group II
      mGluRs, LY354740 did not induce GIRK activation but inhibited voltage-gated Ca2+
      channel currents. 5. These results demonstrate that, in unipolar brush cells,
      native group II mGluRs can functionally couple to activation of GIRKs. Thus, the
      absence of coupling in the majority of CNS neurones examined to date may be due
      to restricted cellular co-localization or co-expression of the appropriate
      proteins.

PMID- 9575286
TI  - Characterization of a Ca2+-activated K+ current in insulin-secreting murine
      betaTC-3 cells.
AB  - 1. The whole-cell perforated-patch recording mode was used to record a Ca2+
      dependent K+ current (IK(Ca)) in mouse betaTC-3 insulin-secreting cells. 2.
      Depolarizing voltage steps (to potentials where Ca2+ currents are activated)
      evoked a slowly activating, outward current, which exhibited a slow deactivation
      (in seconds) upon subsequent hyperpolarization. 3. This current was shown to
      increase with progressively longer depolarizing voltage steps. It could be
      reversibly abolished by the removal of Ca2+ from the external medium or by
      application of Ca2+ channel blockers, such as Cd2+ and nifedipine. It was
      concluded that the depolarization-evoked current was activated by Ca2+. 4.
      Variations in external K+ concentration led to shifts in the reversal potential
      of the Ca2+-dependent current as predicted by the Nernst equation for a K+
      selective current. 5. The Ca2+-activated K+ current was insensitive to external
      TEA (10 mM), a concentration sufficient to block the large-conductance Ca2+
      dependent (maxi-KCa) channel in beta-cells. It was also insensitive to apamin,
      tubocurarine and scyllatoxin (leiurotoxin I), specific blockers of small
      conductance KCa channels. 6. The current was blocked by quinine, a non-specific
      KCa channel blocker and, surprisingly, by charybdotoxin (ChTX; 100 nM) but not
      iberiotoxin, a charybdotoxin analogue, which blocks the maxi-KCa channel. It was
      sensitive to block by clotrimazole and could be potently and reversibly
      potentiated by micromolar concentrations of niflumic acid. Thus, the current
      exhibited unique pharmacological characteristics, not conforming to the known KCa
      channel classes. 7. The ChTX-sensitive KCa channel was permeable to Tl+, K+, Rb+
      and NH4+ but not Cs+ ions. 8. The ChTX-sensitive IK(Ca) could be activated by the
      muscarinic agonists in the presence or absence of external Ca2+, presumably by
      releasing Ca2+ from internal stores. 9. Acutely isolated porcine islet cells also
      exhibited a slow IK(Ca) resembling that described in betaTC-3 cells in kinetic
      properties, insensitivity to TEA (5 mM) and sensitivity to quinidine, an analogue
      of quinine. The porcine IK(Ca), however, was not sensitive to block by 100-200 nM
      ChTX. It is likely, that species differences account for pharmacological
      differences between the mouse and porcine slow IK(Ca).

PMID- 9575287
TI  - Inhibition of N- and P/Q-type calcium channels by postsynaptic GABAB receptor
      activation in rat supraoptic neurones.
AB  - 1. Voltage-dependent Ca2+ currents of dissociated rat supraoptic nucleus (SON)
      neurones were measured using the whole-cell configuration of the patch-clamp
      technique to examine direct postsynaptic effects of GABAB receptor activation on
      SON magnocellular neurones. 2. The selective GABAB agonist baclofen reversibly
      inhibited voltage-dependent Ca2+ currents elicited by voltage steps from a
      holding potential of -80 mV to depolarized potentials in a dose-dependent manner.
      The ED50 of baclofen for inhibiting Ca2+ currents was 1.4 x 10-6 M. Baclofen did
      not inhibit low threshold Ca2+ currents elicited by voltage steps from -120 to 
      40 mV. 3. Inhibition of high threshold Ca2+ currents by baclofen was rapidly and
      completely reversed by the selective GABAB antagonists, CGP 35348 and CGP 55845A,
      when the antagonists were added at the molar ratio vs. baclofen of 10 : 1 and
      0.01 : 1, respectively. It was also reversed by a prepulse to +150 mV lasting for
      100 ms. 4. The inhibition of Ca2+ currents was abolished when the cells were
      pretreated with pertussis toxin for longer than 20 h or with N-ethylmaleimide for
      2 min. It was also abolished when GDPbetaS was included in the patch pipette.
      When GTPgammaS was included in the patch pipette, baclofen produced irreversible
      inhibition of Ca2+ currents and this inhibition was again reversed by the
      prepulse procedure. 5. The inhibition of N-, P/Q-, L- and R-type Ca2+ channels by
      baclofen (10-5 M) was 24.1, 10.5, 3.1 and 3. 6 %, respectively, of the total Ca2+
      currents. Only the inhibition of N- and P/Q-types was significant. 6. These
      results suggest that GABAB receptors exist in the postsynaptic sites of the SON
      magnocellular neurones and mediate selective inhibitory actions on voltage
      dependent Ca2+ channels of N- and P/Q-types via pertussis toxin-sensitive G
      proteins, and that such inhibitory mechanisms may play a role in the regulation
      of SON neurones by the GABA neurones.

PMID- 9575288
TI  - Developmental changes in the expression of low-voltage-activated Ca2+ channels in
      rat visual cortical neurones.
AB  - 1. The functional properties of low-voltage-activated (LVA) Ca2+ channels were
      studied in pyramidal neurones from different rat visual cortical layers in order
      to investigate changes in their properties during early postnatal development.
      Ca2+ currents were recorded in brain slices using the whole-cell patch-clamp
      technique in rats from three age groups: 2, 3 and 12 days old (postnatal day (P)
      2, P3 and P12). 2. It was demonstrated that LVA Ca2+ currents are present in
      neurones from superficial (I-II) and deep (V-VI) visual cortex layers of P2 and
      P3 rats. No LVA Ca2+ currents were observed in neurones from the middle (III-IV)
      layers of these rats. The LVA Ca2+ currents observed in P2 and P3 neurones from
      both superficial and deep layers could be completely blocked by nifedipine (100
      microM) and were insensitive to Ni2+ (25 microM). 3. The density of LVA Ca2+
      currents decreased rapidly during the early stages of postnatal development,
      while the density of high-voltage-activated (HVA) Ca2+ currents progressively
      increased up to the twelfth postnatal day. No LVA Ca2+ currents were found in P12
      neurones from any of the layers. Only HVA Ca2+ currents with high sensitivity to
      F- applied through the patch pipette were observed. 4. The kinetics of LVA Ca2+
      currents could be well approximated by the m2h Hodgkin-Huxley equation with an
      inactivation time constant of 24 +/- 6 ms. The steady-state inactivation curve
      fitted by a Boltzmann function had the following parameters: membrane potential
      at half-inactivation, -86.9 mV; steepness coefficient,3.4 mV. 5. It is concluded
      that, in visual cortical neurones, LVA Ca2+ channels are expressed only in the
      neurones of deep and superficial layers over a short period during the earliest
      postnatal stages. These channels are nifedipine sensitive and similar in
      functional properties to those in the laterodorsal (LD) thalamic nucleus.
      However, the cortical neurones do not express another ('slow') type of LVA Ca2+
      channel, which is permanently present in LD thalamic neurones after the second
      postnatal week, indicating that the developmental time course of cortical and
      thalamic cells is different.

PMID- 9575289
TI  - Multiple modulatory effects of dopamine on calcium channel kinetics in adult rat
      sensory neurons.
AB  - 1. The aim of this research was to study the modulatory effects induced on high
      voltage-activated (HVA) calcium channels and pharmacologically isolated subtypes
      through dopamine receptor activation. 2. The experiments were carried out on
      acutely isolated adult rat sensory neurons, recorded by means of the whole-cell
      patch-clamp technique. 3. At saturating concentrations dopamine was effective in
      inducing: (a) a voltage-dependent prolongation of activation kinetics, (b) a
      voltage-independent scaling down of the currents without any changes in
      activation and inactivation kinetics, and (c) an acceleration of inactivation
      kinetics, not affected by a positive conditioning prepulse. 4. These three
      inhibitory effects were observed on N- and P/Q-type currents, whereas only a
      voltage-independent scaling up and/or scaling down was observed on L-type
      current. 5. The inhibitory effects were sometimes observed in isolation in
      different neurons, but more frequently they were variously combined in the same
      cell. A correlation analysis of these effects shows no relationship between them,
      corroborating the conclusion that they are mechanistically distinct. 6. The
      existence of an inactivating effect accounts for the occurrence of a voltage
      dependent inhibitory effect in some cells without an apparent slowing down of
      activation kinetics, since the increased inactivation may mask the slow component
      of the activation. 7. The multiple modulatory effects on calcium channels, even
      on pharmacologically separated N-, L- and P/Q-currents, suggest that
      pharmacological and functional classifications do not necessarily match
      completely. 8. The multiple modulatory effects on HVA calcium currents may play a
      prominent role both in controlling the integrative properties of neurons and in
      regulating output at a presynaptic level.

PMID- 9575291
TI  - Developmental changes in calcium channel types mediating synaptic transmission in
      rat auditory brainstem.
AB  - 1. Calcium channel blockers were tested on excitatory postsynaptic currents
      (EPSCs) at the synapse formed by the calyx of Held on the principal cells in the
      medial nucleus of trapezoid body (MNTB) in brainstem slices of 4- to 14-day-old
      rats. 2. At postnatal day 4-9 (P4-9), EPSCs were irreversibly suppressed by the
      P/Q-type Ca2+ channel blocker omega-agatoxin-IVA (omega-Aga-IVA, 200 nM) and also
      by the N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CgTx, 2 microM). A
      small fraction of EPSCs was resistant to both toxins but abolished by Cd2+ (100
      microM). 3. After P7, the omega-CgTx-sensitive EPSC fraction diminished and
      eventually disappeared after P10. Concomitantly the fraction insensitive to both
      toxins decreased and became undetectable after P10. 4. In contrast, the omega-Aga
      IVA-sensitive EPSC fraction increased with development and became predominant
      after P10. All through the developmental period examined, the L-type Ca2+ channel
      blocker nicardipine (10 microM) had no effect. 5. We conclude that presynaptic
      Ca2+ channel types triggering transmitter release undergo developmental switching
      during the early postnatal period.

PMID- 9575290
TI  - The antagonist trinitrophenyl-ATP reveals co-existence of distinct P2X receptor
      channels in rat nodose neurones.
AB  - 1. Whole-cell recordings were made from rat nodose ganglion neurones in culture
      and from human embryonic kidney (HEK293) cells stably transfected to express
      P2X2, P2X3 or both receptor subunits. We examined the blocking actions of 2',3'-O
      trinitrophenyl-ATP (TNP-ATP) on currents evoked by the agonists ATP and alpha,
      beta-methylene ATP. 2. In cells expressing only P2X2 or P2X3 receptor subunits,
      the inhibition by TNP-ATP was fitted by a single binding site model with half
      maximal concentrations of about 3 microM and 3 nM, respectively. In cells
      expressing both P2X2 and P2X3 receptor subunits, currents showed little or no
      desensitization, thus excluding contributions from homomeric P2X3 receptors. When
      alpha,beta-methylene ATP was the agonist (activating heteromeric P2X2/3
      receptors), the inhibition by TNP-ATP conformed to a single binding site (half
      maximal concentration about 3 nM). When ATP (30 microM) was the agonist,
      activating both heteromeric P2X2/3 as well as homomeric P2X2 receptors, the
      inhibition curve was biphasic (half-maximal concentrations about 3 nM and 3
      microM); the proportion of high affinity sites in all six cells tested was about
      40 %. 3. In nodose ganglion neurones, the inhibition by TNP-ATP of currents
      evoked by ATP (30 microM) was also clearly biphasic. In this case, individual
      neurones showed more variability in the proportion of high and low affinity sites
      for TNP-ATP. 4. We conclude that more than one form of multimeric P2X receptor
      channels are functionally expressed on the cell bodies of individual nodose
      ganglion neurones. On the basis of sensitivity to TNP-ATP, and other properties,
      one of these may correspond to the homomeric P2X2 receptor and the other(s) to
      heteromeric P2X2/3 receptors.

PMID- 9575292
TI  - Presynaptic calcium channels mediating synaptic transmission in submucosal
      neurones of the guinea-pig caecum.
AB  - 1. Intracellular recording techniques were used to examine the voltage-activated
      calcium channels mediating neurotransmitter release from nerve terminals of
      extrinsic, sympathetic origin and intrinsic (enteric) origin innervating
      submucosal neurones of the guinea-pig caecum. 2. The noradrenergic slow
      inhibitory postsynaptic potential (IPSP) was abolished by superfusion of omega
      conotoxin (omega-CTX) GVIA (3-300 nM), with an apparent IC50 of 8.6 nM.
      Superfusion of omega-CTX MVIIC (500 nM) also suppressed the amplitude of slow
      IPSPs, but both omega-agatoxin IVA (100 nM) and nicardipine (1-10 microM) were
      ineffective. The hyperpolarization induced by exogenous noradrenaline was not
      affected by omega-CTX GVIA (100 nM). 3. In contrast to the slow IPSP, the
      amplitude of the cholinergic fast excitatory postsynaptic potential (EPSP) was
      partially inhibited, but not abolished, by omega-CTX GVIA (0.1-1 microM).
      Furthermore, omega-agatoxin IVA (0.1-1 microM) or omega-CTX MVIIC (0.1-1 microM)
      also affected the fast EPSP, but nicardipine (1-10 microM) was ineffective. In
      combination, omega-CTX GVIA (100 nM) and omega-agatoxin IVA (100 nM) inhibited
      the fast EPSP by 74 +/- 6 %; the residual fast EPSP was not affected by omega-CTX
      MVIIC (100 nM). The fast EPSP was completely abolished by low Ca2+, high Mg2+
      Krebs solution or Krebs solution containing Co2+ (2 mM) and Cd2+ (400 microM).
      The depolarization induced by exogenous acetylcholine was not affected by either
      omega-CTX GVIA (100 nM), omega-agatoxin IVA (100 nM) or omega-CTX MVIIC (100 nM).
      4. Taken together, these results suggest that, in the submucosal plexus of the
      guinea-pig caecum, release of noradrenaline from extrinsic nerve terminals is
      regulated by N-type calcium channels, whereas release of acetylcholine from
      intrinsic nerve terminals involves several types of calcium channel.

PMID- 9575293
TI  - Dissociation between electrical and mechanical responses to nitrergic stimulation
      in the canine gastric fundus.
AB  - 1. We examined the relationships between membrane potential, intracellular [Ca2+]
      ([Ca2+]i), and tension in muscles of the canine gastric fundus in response to
      nitrergic stimulation by NO donors and electrical field stimulation (EFS) of
      intrinsic enteric inhibitory neurons when adrenergic and cholinergic responses
      were blocked. 2. NO donors reduced [Ca2+]i and tension in a concentration
      dependent manner. A close relationship was noted between these parameters. 3. In
      terms of the [Ca2+] vs. force relationship, relaxation responses to EFS differed
      from responses to NO donors. EFS resulted in smaller decreases in [Ca2+]i to
      produce a given relaxation compared with responses to NO donors. Thus, muscles
      stimulated with EFS were less sensitive to [Ca2+]i than muscles stimulated with
      exogenous NO. 4. When membrane potential, [Ca2+]i and tension were monitored
      simultaneously in the same muscles, a temporal dissociation was noted between the
      electrical responses and changes in [Ca2+]i and tension. Brief electrical
      responses were associated with more sustained changes in [Ca2+]i and tension. 5.
      Further dissociation between electrical and mechanical effects was noted. Changes
      in [Ca2+]i and tension caused by sodium nitroprusside and EFS were blocked by
      arginine analogues and by oxyhaemoglobin, but electrical responses were
      unaffected. 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ), an inhibitor of
      soluble guanylyl cyclase, also blocked the effects of nitrergic stimulation on
      [Ca2+]i and tension, without affecting hyperpolarization. Thus, in the presence
      of continued hyperpolarization, the reductions in [Ca2+]i and tension caused by
      nitrergic stimulation were blocked. 6. Block of hyperpolarization in response to
      nitrergic stimulation with tetrapentylammonium chloride (TPEA) had relatively
      little effect on the [Ca2+]i and tension responses. Thus, hyperpolarization is
      not required for nitrergic effects on [Ca2+]i and tension. 7. In summary,
      reduction in [Ca2+]i and tension in response to nitrergic stimulation of the
      canine gastric fundus does not depend upon electrical hyperpolarization. Non
      electrical mechanisms such as enhanced uptake of Ca2+ by the sarcoplasmic
      reticulum or reduction in the Ca2+ sensitivity of the contractile apparatus may
      be the primary mechanisms mediating nitrergic responses in these muscles.

PMID- 9575294
TI  - Intracellular recordings in thalamic neurones during spontaneous spike and wave
      discharges in rats with absence epilepsy.
AB  - 1. In vivo extracellular and intracellular recordings were performed from
      thalamocortical (TC) neurones in a genetic model of absence epilepsy (genetic
      absence epilepsy rats from Strasbourg) during spontaneous spike and wave
      discharges (SWDs). 2. Extracellularly recorded single units (n = 14) fired either
      a single action potential or a high frequency burst of up to three action
      potentials, concomitantly with the spike component of the spike-wave complex. 3.
      Three main events characterized the intracellular activity of twenty-six out of
      twenty-eight TC neurones during SWDs: a small amplitude tonic hyperpolarization
      that was present throughout the SWD, rhythmic sequences of EPSP/IPSPs occurring
      concomitantly with the spike-wave complexes, and a small tonic depolarization at
      the end of the SWD. The rhythmic IPSPs, but not the tonic hyperpolarization, were
      mediated by activation of GABAA receptors since they reversed in polarity at -68
      mV and appeared as depolarizing events when recording with KCl-filled electrodes.
      4. The intracellular activity of the remaining two TC neurones consisted of
      rhythmic low threshold Ca2+ potentials, with a few EPSP/IPSP sequences present at
      the start of the SWD. 5. These results obtained in a well-established genetic
      model of absence epilepsy do not support the hypothesis that the intracellular
      activity of TC neurones during SWDs involves rhythmic sequences of GABAB IPSPs
      and low threshold Ca2+ potentials.

PMID- 9575295
TI  - Interaction of the Na+-K+ pump and Na+-Ca2+ exchange via [Na+]i in a restricted
      space of guinea-pig ventricular cells.
AB  - 1. The whole-cell Na+-K+ pump current (INa-K) and Na+-Ca2+ exchange current (INa
      Ca) were recorded in guinea-pig ventricular myocytes to study the interaction
      between the two Na+ transport mechanisms. 2. INa-K was isolated as an external K+
      induced current, and INa-Ca as an external Ca2+- induced or Ni2+-sensitive
      current. The experimental protocol used for one ion carrier did not affect the
      other. 3. The amplitude of INa-K decreased to 54 +/- 17 % of the initial peak
      during continuous application of K+ with 20 mM Na+ in the pipette. The outward
      INa-Ca, which was intermittently activated by brief applications of Ca2+,
      decreased during activation of INa-K, and recovered after cessation of INa-K
      activation. These findings revealed a dynamic interaction between INa-K and INa
      Ca via a depletion of Na+ under the sarcolemma. 4. To estimate changes in Na+
      concentration ([Na+]i) under the sarcolemma, the reversal potential (Vrev) of INa
      Ca was measured. Unexpectedly, Vrev hardly changed during activation of INa-K.
      However, when INa-Ca was blocked by Ni2+ at the same time that INa-K was
      activated, Vrev changed markedly, maximally by +100 mV, immediately after the
      removal of Ni2+ and K+. 5. Subsarcolemmal [Na+]i was calculated from the Vrev of
      INa-Ca on the assumption that the subsarcolemmal Ca2+ concentration ([Ca2+]i) was
      fixed with EGTA, and mean [Na+]i was calculated from both the time integral of
      INa-K and the cell volume. The subsarcolemmal [Na+]i was about seven times
      greater than the mean [Na+]i. 6. The interaction between the Na+-K+ pump and Na+
      Ca2+ exchange was well simulated by a diffusion model, in which Na+ diffusion was
      restricted to one-seventh (14 %) of the total cell volume.

PMID- 9575296
TI  - Out-of-equilibrium pH transients in the guinea-pig ventricular myocyte.
AB  - 1. Following an intracellular alkali load (imposed by acetate prepulsing in
      CO2/HCO3- buffer), intracellular pH (pHi) of the guinea-pig ventricular myocyte
      (recorded from intracellular SNARF fluorescence) recovers to control levels.
      Recovery has two phases. An initial rapid phase (lasting up to 2 min) is followed
      by a later slow phase (several minutes). Inhibition of sarcolemmal acid-loading
      carriers (by removal of extracellular Cl-) inhibits the later, slow phase but the
      initial rapid recovery phase persists. It also persists in the absence of
      extracellular Na+ and in the presence of the HCO3- transport inhibitor DIDS (4,4
      di-isothiocyanatostilbene-2, 2-disulphonic acid). 2. The rapid recovery phase is
      not evident if the alkali load has been induced by reducing PCO2 (from 10 to 5
      %), and it is inhibited in the absence of CO2/HCO3- buffer (i.e. Hepes buffer).
      It is also slowed by the carbonic anhydrase (CA) inhibitor acetazolamide (ATZ).
      We conclude that it is caused by buffering of the alkali load through the
      hydration of intracellular CO2 (CO2-dependent buffering). 3. The time course of
      rapid recovery is consistent with an intracellular CO2 hydration rate constant
      (k1) of 0.36 s-1 in the presence of CA activity, and 0.14 s-1 in the absence of
      CA activity. This latter k1 value matches the literature value for uncatalysed
      CO2 hydration in free solution. Natural CO2 hydration is accelerated 2.6-fold in
      the ventricular myocyte by endogenous CA. 4. The rapid recovery phase represents
      a period when the intracellular CO2/HCO3- buffer is out of equilibrium (OOE).
      Modelling of the recovery phase using our k1 value, indicates that OOE conditions
      will normally extend for at least 2 min following a step rise in pHi (at constant
      PCO2). If CA is inactive, this period can be as long as 5 min. During normal pHi
      regulation, the recovery rate during these periods cannot be used as a measure of
      sarcolemmal acid loading since it is a mixture of slow CO2-dependent buffering
      and transmembrane acid loading. The implication of this finding for
      quantification of pHi regulation during alkalosis is discussed.

PMID- 9575297
TI  - Sarcolemmal mechanisms for pHi recovery from alkalosis in the guinea-pig
      ventricular myocyte.
AB  - 1. The mechanism of pHi recovery from an intracellular alkali load (induced by
      acetate prepulse or by reduction/removal of ambient PCO2) was investigated using
      intracellular SNARF fluorescence in the guinea-pig ventricular myocyte. 2. In
      Hepes buffer (pHo 7.40), pHi recovery was inhibited by removal of extracellular
      Cl-, but not by removal of Na+o or elevation of K+o. Recovery was unaffected by
      the stilbene drug DIDS (4,4-diisothiocyanatostilbene-disulphonic acid), but was
      slowed dose dependently by the stilbene drug DBDS (dibenzamidostilbene
      disulphonic acid). 3. In 5 % CO2/HCO3- buffer (pHo 7.40), pHi recovery was faster
      than in Hepes buffer. It consisted of an initial rapid recovery phase followed by
      a slow phase. Much of the rapid phase has been attributed to CO2-dependent
      buffering. The slow phase was inhibited completely by Cl-o removal but not by
      Na+o removal or K+o elevation. 4. At a test pHi of 7.30 in CO2/HCO3- buffer, the
      slow phase was inhibited 70 % by DIDS. The mean DIDS-inhibitable acid influx was
      equivalent in magnitude to the HCO3--stimulated acid influx. Similarly, the DIDS
      insensitive influx was equivalent to that estimated in Hepes buffer. 5. We
      conclude that two independent sarcolemmal acid-loading carriers are stimulated by
      a rise of pHi and account for the slow phase of recovery from an alkali load. The
      results are consistent with activation of a DIDS-sensitive Cl--HCO3- anion
      exchanger (AE) to produce HCO3- efflux, and a DIDS-insensitive Cl--OH- exchanger
      (CHE) to produce OH- efflux. H+-Cl- co-influx as the alternative configuration
      for CHE is not, however, excluded. 6. The dual acid-loading system (AE plus CHE),
      previously shown to be activated by a fall of extracellular pH, is thus activated
      by a rise of intracellular pH. Activity of the dual-loading system is therefore
      controlled by pH on both sides of the cardiac sarcolemma.

PMID- 9575298
TI  - Release of acetylcholine from embryonic myocytes in Xenopus cell cultures.
AB  - 1. Acetylcholine (ACh) is important as the transmitter responsible for
      neuromuscular transmission. Here we report the non-quantal release of ACh from
      embryonic myocytes. 2. Co-cultures of spinal neurons and myotomal muscle cells
      were prepared from 1-day-old Xenopus embryos. Single channel currents were
      recorded in the non-innervated myocytes. When the patch pipette was filled with
      Ringer solution alone, spontaneous single channel currents occurred, which were
      inhibited by d-tubocurarine (d-Tc). 3. The channel conductance appearing in
      Ringer solution (37.3 pS) was similar to that of an embryonic-type ACh channel
      (36.9 pS), indicating that ACh is probably released from myocytes in normal
      Ringer solution. 4. When the patch pipette was filled with anticholinesterase
      alone to prevent hydrolysis of ACh released from myocytes, both physostigmine and
      neostigmine in a concentration-dependent manner increased channel open
      probability; it was reduced by d-Tc or alpha-bungarotoxin. 5. Vesamicol and
      quinacrine, vesicular transporter inhibitors, reduced the channel open
      probability caused by ACh released from myocytes in the presence of neostigmine
      or physostigmine. 6. Intracellular alkalinization with NH4Cl inhibited the ACh
      release from myocytes, whereas, extracellular alkalinization, brought about by
      replacing normal Ringer solution, with pH 8.6 Ringer solution enhanced ACh
      release. 7. The immunocytochemistry of choline acetyltransferase (ChAT) showed
      that ChAT exists in both myocytes and neuronal cells but not in fibroblasts. 8.
      These results suggest that embryonic myocytes are capable of synthesizing and
      releasing ACh in a non-quantal manner. Extracellular alkalinization enhanced and
      intracellular alkalinization inhibited ACh release from myocytes.

PMID- 9575300
TI  - Chemoafferent degeneration and carotid body hypoplasia following chronic
      hyperoxia in newborn rats.
AB  - 1. To define the role of environmental oxygen in regulating postnatal maturation
      of the carotid body afferent pathway, light and electron microscopic methods were
      used to compare chemoafferent neurone survival and carotid body development in
      newborn rats reared from birth in normoxia (21 % O2) or chronic hyperoxia (60 %
      O2). 2. Four weeks of chronic hyperoxia resulted in a significant 41 % decrease
      in the number of unmyelinated axons in the carotid sinus nerve, compared with age
      matched normoxic controls. In contrast, the number of myelinated axons was
      unaffected by hyperoxic exposure. 3. Chemoafferent neurones, located in the
      glossopharyngeal petrosal ganglion, already exhibited degenerative changes
      following 1 week of hyperoxia from birth, indicating that even a relatively short
      hyperoxic exposure was sufficient to derange normal chemoafferent development. In
      contrast, no such changes were observed in the vagal nodose ganglion,
      demonstrating that the effect of high oxygen levels was specific to sensory
      neurones in the carotid body afferent pathway. Moreover, petrosal ganglion
      neurones were sensitive to hyperoxic exposure only during the early postnatal
      period. 4. Chemoafferent degeneration in chronically hyperoxic animals was
      accompanied by marked hypoplasia of the carotid body. In view of previous
      findings from our laboratory that chemoafferent neurones require trophic support
      from the carotid body for survival after birth, we propose that chemoafferent
      degeneration following chronic hyperoxia is due specifically to the loss of
      target tissue in the carotid body.

PMID- 9575299
TI  - Role of adenosine and its receptors in the vasodilatation induced in the cerebral
      cortex of the rat by systemic hypoxia.
AB  - 1. In anaesthetized rats, we have examined the role of adenosine in
      vasodilatation evoked in the cerebral cortex by systemic hypoxia (breathing 8 %
      O2). Red cell flux was recorded from the surface of the exposed parietal cortex
      (CoRCF) by a laser Doppler probe, cortical vascular conductance (CoVC) being
      computed as CoRCF divided by mean arterial blood pressure. All agonists and
      antagonists were applied topically to the cortex. 2. Systemic hypoxia or
      adenosine application for 5 or 10 min, respectively, induced an increase in CoRCF
      and CoVC. These responses were substantially reduced by 8-phenyltheophylline (8
      PT), an adenosine receptor antagonist which is non-selective between the
      adenosine A1 and A2A receptor subtypes. By contrast, the adenosine receptor
      antagonist 8-sulphophenyltheophylline (8-SPT) which is similarly non-selective,
      but unlike 8-PT, does not cross the blood-brain barrier, reduced the increases in
      CoRCF and CoVC induced by adenosine, but had no effect on those induced by
      hypoxia. 3. The A2A receptor agonist CGS21680 produced a substantial increase in
      CoRCF and CoVC, but the A1 receptor agonist 2-chloro-N6-cyclopentyladenosine had
      minimal effects. 4. The A2A receptor antagonist ZM241385 reduced the increase in
      CoRCF and CoVC induced by adenosine and reduced the increase in CoRCF induced by
      hypoxia. 5. We propose that exogenous adenosine that is topically applied to the
      cerebral cortex produces vasodilatation by acting on A2A receptors on the
      vascular smooth muscle. However, during systemic hypoxia, we propose that
      adenosine is released from endothelial cells and acts on endothelial A2A
      receptors to produce the major part of the hypoxia-induced dilatation in the
      cerebral cortex.

PMID- 9575301
TI  - Multiple pathways for L-methionine transport in brush-border membrane vesicles
      from chicken jejunum.
AB  - 1. The intestinal transport of L-methionine has been investigated in brush-border
      membrane vesicles isolated from the jejunum of 6-week-old chickens. L-Methionine
      influx is mediated by passive diffusion and by Na+-dependent and Na+-independent
      carrier-mediated mechanisms. 2. In the absence of Na+, cis-inhibition experiments
      with neutral and cationic amino acids indicate that two transport components are
      involved in L-methionine influx: one sensitive to L-lysine and the other
      sensitive to 2-aminobicyclo[2.2. 1]heptane-2-carboxylic acid (BCH). The L-lysine
      sensitive flux is strongly inhibited by L-phenylalanine and can be broken down
      into two pathways, one sensitive to N-ethylmaleimide (NEM) and the other to L
      glutamine and L-cystine. 3. The kinetics of L-methionine influx in Na+-free
      conditions is described by a model involving three transport systems, here called
      a, b and c: systems a and b are able to interact with cationic amino acids but
      differ in their kinetic characteristics (system a: Km = 2.2 +/- 0.3 microM and
      Vmax = 0.13 +/- 0.005 pmol (mg protein)-1 (2 s)-1; system b: Km = 3.0 +/- 0.3 mM
      and Vmax = 465 +/- 4.3 pmol (mg protein)-1 (2 s)-1); system c is specific for
      neutral amino acids, has a Km of 1.29 +/- 0.08 mM and a Vmax of 229 +/- 5.0 pmol
      (mg protein)-1 (2 s)-1 and is sensitive to BCH inhibition. 4. The Na+-dependent
      component can be inhibited by BCH and L-phenylalanine but cannot interact either
      with cationic amino acids or with alpha-(methylamino)isobutyrate (MeAIB). 5. The
      kinetic analysis of L-methionine influx under a Na+ gradient confirms the
      activity of the above described transport systems a and b. System a is not
      affected by the presence of Na+ while system b shows a 3-fold decrease in the
      Michaelis constant and a 1.4-fold increase in Vmax. In the presence of Na+, the
      BCH-sensitive component can be subdivided into two pathways: one corresponds to
      system c and the other is Na+ dependent and has a Km of 0.64 +/- 0. 013 mM and a
      Vmax of 391 +/- 2.3 pmol (mg protein)-1 (2 s)-1. 6. It is concluded that L
      methionine is transported in the chicken jejunum by four transport systems, one
      with functional characteristics similar to those of system bo, + (system a); a
      second (system b) similar to system y+, which we suggest naming y+m to account
      for its high Vmax for L-methionine transport in the absence of Na+; a third
      (system c) which is Na+ independent and has similar properties to system L; and a
      fourth showing Na+ dependence and tentatively identified with system B.

PMID- 9575302
TI  - Mediation by 5_hydroxytryptamine of the femoral vasoconstriction induced by acid
      challenge of the rat gastric mucosa.
AB  - 1. Gastric mucosal barrier disruption in the presence of luminal acid causes
      femoral vasoconstriction via a pathway that appears to be stimulated by
      messengers generated in the injured gastric mucosa. This study was undertaken to
      analyse the gastric factors that are responsible for the femoral vasoconstrictor
      response. 2. Gastric mucosal barrier disruption in the presence of luminal acid
      was induced by perfusing the stomach of urethane-anaesthetized rats with ethanol
      (15 %) in 0.01-0.15 M HCl. Blood flow in the left gastric and right femoral
      artery was estimated by the ultrasonic transit time shift technique. 3. Gastric
      perfusion of ethanol in HCl caused loss of H+ ions from the gastric lumen,
      decreased the HCO3- concentration in hepatic portal vein blood, induced
      macroscopic histological damage to the gastric mucosa, dilated the left gastric
      artery and constricted the femoral artery. These responses were related to the
      HCl concentration in the ethanol-containing perfusion medium. 4. The femoral
      vasoconstriction was also seen when, instead of ethanol, taurocholate (20 mM) was
      used to disrupt the gastric mucosal barrier in the presence of 0.15 M HCl. 5. The
      femoral vasoconstriction evoked by gastric perfusion of ethanol in HCl was left
      unaltered by pharmacological blockade of gastrin and histamine receptors. In
      contrast, the 5-hydroxytryptamine 5-HT1/2 receptor antagonist methiothepin, but
      not the 5-HT2A receptor antagonist ketanserin or the 5-HT3 receptor antagonist
      granisetron, inhibited the ability of both 5-hydroxytryptamine and gastric acid
      back-diffusion to constrict the femoral artery. 6. Gastric acid back-diffusion
      caused release of 5-hydroxytryptamine into the gastric lumen, which was related
      to the HCl concentration in the ethanol-containing perfusion medium. 7. These
      data show that femoral vasoconstriction evoked by gastric mucosal barrier
      disruption depends on back-diffusion of acid into the mucosa. The acid-induced
      damage results in release of 5-hydroxytryptamine from the gastric mucosa, and the
      pathway leading to constriction of the femoral artery involves 5
      hydroxytryptamine acting via 5-HT1/2 receptors as a messenger molecule.

PMID- 9575303
TI  - Effect of transverse-tubular chloride conductance on excitability in skinned
      skeletal muscle fibres of rat and toad.
AB  - 1. The influence of the transverse-tubular (T-) system Cl- conductance on
      membrane excitability in skeletal muscle fibres of toad and rat was examined
      because of conflicting conclusions of previous studies on Cl- conductance. A
      mechanically skinned fibre preparation was used that permitted investigation of
      Ca2+ release via the normal T-system voltage-sensor mechanism after complete
      removal of the surface membrane, which thereby allowed estimation of the T-system
      potential from force measurements. 2. When a skinned fibre was bathed in a high
      [K+] solution, the sealed T-system became polarized and could be rapidly
      depolarized by replacing the K+ with Na+, thereby eliciting Ca2+ release from the
      sarcoplasmic reticulum. In rat skinned fibres, addition of 20 mM Cl- to the
      'myoplasm' (i.e. bathing solution) partially depolarized the T-system, inducing
      Ca2+ release and subsequent voltage-sensor inactivation. These effects were
      completely abolished with 100 microM of the Cl- channel blocker 9-anthracene
      carboxylic acid (9-AC). Voltage-sensor inactivation increased in a graded manner
      over the range 3-20 mM myoplasmic Cl-. 3. In toad fibres, voltage-sensor
      inactivation was only detectable at > 10 mM myoplasmic Cl-, and 20 mM Cl- was
      only able to depolarize the T-system sufficiently to trigger Ca2+ release if the
      myoplasmic [K+] was reduced by 50 %. In toad fibres, 100 microM 9-AC caused
      little if any block of the T-system Cl- conductance. 4. It was also found that
      when skinned fibres were obtained from muscles that had been bathed in a zero Cl-
      extracellular solution, the initial Na+ substitutions were more effective at
      depolarizing the T-system. This is consistent with Cl- trapped in the sealed T
      system exerting a polarizing effect on T-system potential. 5. These results
      unequivocally demonstrate that there is a large 9-AC-sensitive Cl- conductance in
      the T-system of rat fibres, and a smaller, though still appreciable, Cl-
      conductance in the T-system of toad fibres, which is relatively insensitive to 9
      AC. The results are important for understanding the basis of the Cl- channel
      aberration in myotonia.

PMID- 9575304
TI  - Effect of hydrogen peroxide and dithiothreitol on contractile function of single
      skeletal muscle fibres from the mouse.
AB  - 1. We used intact single fibres from a mouse foot muscle to study the role of
      oxidation-reduction in the modulation of contractile function. 2. The oxidant
      hydrogen peroxide (H2O2, 100-300 microM) for brief periods did not change
      myoplasmic Ca2+ concentrations ([Ca2+]i) during submaximal tetani. However, force
      increased by 27 % during the same contractions. 3. The effects of H2O2 were time
      dependent. Prolonged exposures resulted in increased resting and tetanic [Ca2+]i,
      while force was significantly diminished. The force decline was mainly due to
      reduced myofibrillar Ca2+ sensitivity. There was also evidence of altered
      sarcoplasmic reticulum (SR) function: passive Ca2+ leak was increased and Ca2+
      uptake was decreased. 4. The reductant dithiothreitol (DTT, 0.5-1 mM) did not
      change tetanic [Ca2+]i, but decreased force by over 40 %. This was completely
      reversed by subsequent incubations with H2O2. The force decline induced by
      prolonged exposure to H2O2 was reversed by subsequent exposure to DTT. 5. These
      results show that the elements of the contractile machinery are differentially
      responsive to changes in the oxidation-reduction balance of the muscle fibres.
      Myofibrillar Ca2+ sensitivity appears to be especially susceptible, while the SR
      functions (Ca2+ leak and uptake) are less so.

PMID- 9575306
TI  - Induction of histidine decarboxylase in skeletal muscle in mice by electrical
      stimulation, prolonged walking and interleukin-1.
AB  - 1. In normal non-exercised skeletal muscles in mice, the activity of histidine
      decarboxylase (HDC), the enzyme which forms histamine, was very low. 2. HDC
      activity in the quadriceps femoris muscle was markedly elevated following
      contractions evoked by even a few minutes of direct electrical stimulation,
      peaking at 8-12 h following contraction lasting 10 min, and gradually decreasing
      during the 24 h following contraction. The elevation in HDC activity depended on
      the duration and strength of stimulation. 3. Direct electrical stimulation
      induced a quantitatively similar elevation of HDC activity in the muscles of mast
      cell-deficient mice (W/Wv mice). 4. Prolonged walking at a speed of 6 m min-1 for
      up to 6 h with a 30 min rest period at 3 h also elevated muscle HDC activity, the
      magnitude of the elevation being related to the duration of the walking. Repeated
      exercise (training) for several days diminished the elevation of muscle HDC
      activity induced by walking. In contrast, starvation augmented the elevation of
      muscle HDC activity induced by walking. 5. Intraperitoneal injection of
      interleukin-1beta (IL-1beta) also elevated muscle HDC activity in a dose
      dependent manner, as little as 1 microg kg-1 of IL-1 producing a significant
      elevation of muscle HDC activity. 6. IL-1beta was immunohistochemically detected
      in normal non-exercised quadriceps femoris muscle. We could not detect a
      significant increase in IL-1beta after exercise in the muscle or in serum: it may
      be below the level of detection. 7. On the basis of these results, together with
      those reported previously and the known actions of histamine, we propose that an
      elevation of HDC activity and generation of histamine occur in skeletal muscle
      following muscle contraction possibly as a result of induction by IL-1beta and
      that the histamine may be involved in fatigue in skeletal muscle as part of a
      defence mechanism preventing damage to the muscle.

PMID- 9575305
TI  - Effect of nitric oxide on single skeletal muscle fibres from the mouse.
AB  - 1. Single skeletal muscle fibres from a mouse foot muscle were used to
      investigate the effects of nitric oxide on contractile function. 2. We measured
      force production and myoplasmic free Ca2+ concentration ([Ca2+]i) in single
      fibres exposed to the nitric oxide donors S-nitroso-N-acetylcysteine (SNAC) and
      nitroprusside. 3. The nitric oxide donors reduced myofibrillar Ca2+ sensitivity,
      whereas [Ca2+]i transients were increased during submaximal tetani. Force was
      largely unchanged. SNAC did not change maximum shortening velocity, the rate of
      force redevelopment, or force production at saturating [Ca2+]i. 4. The guanylyl
      cyclase inhibitor LY83583 increased tetanic [Ca2+]i but had no effect on Ca2+
      sensitivity. LY83583 did not prevent the decrease in myofibrillar Ca2+
      sensitivity in response to SNAC. The oxidizer sodium nitrite increased tetanic
      [Ca2+]i and decreased myofibrillar Ca2+ sensitivity. 5. We conclude that under
      our experimental conditions nitric oxide impairs Ca2+ activation of the actin
      filaments which results in decreased myofibrillar Ca2+ sensitivity.

PMID- 9575307
TI  - Antioxidant-oxidant balance in the glomerulus and proximal tubule of the rat
      kidney.
AB  - 1. Antioxidant and oxidative enzymes were examined in renal glomeruli and
      proximal tubules of healthy young rats (10-12 weeks old), and results were
      related to the superoxide anion generation of these tissues. 2. Activities of
      superoxide dismutases, catalase, and glutathione peroxidase were 3- to 6-fold
      higher in proximal tubules than in glomeruli. Similarly, enzyme levels and mRNA
      levels of superoxide dismutases and catalase were significantly higher in
      proximal tubules. 3. NADH- and NADPH-dependent oxidase activity and xanthine
      oxidase activity were not different in glomeruli and proximal tubules. 4.
      Measurements with lucigenin-enhanced chemiluminescence in vital tissues indicated
      10-fold higher rates of superoxide anion in glomeruli than in tubules. 5.
      Compared with the young rats, tubules of 8-month-old rats had significantly
      higher superoxide anion rates and lower superoxide dismutase activity, whereas
      NADH- and NADPH-dependent oxidase activities were unchanged. 6. We conclude that
      considerable differences in the antioxidant-oxidant balance exist between the
      glomerulus and proximal tubule. Results from experiments using chemiluminescence
      in vital tissues suggest that changes in the antioxidant-oxidant balance have an
      effect on oxygen radical levels. The relevance of the observed differences to
      glomerular and tubulo-interstitial disease remains to be determined, but a
      greater susceptibility of the glomerulus to oxidant stress might be anticipated.

PMID- 9575308
TI  - Paired-pulse magnetic stimulation of the human motor cortex: differences among I
      waves.
AB  - 1. In paired-pulse cortical stimulation experiments, conditioning subthreshold
      stimuli suppress the electromyographic (EMG) responses of relaxed muscles to
      suprathreshold magnetic test stimuli at short interstimulus intervals (ISIs) (1-5
      ms) and facilitate them at long ISIs (8-15 ms). 2. We made paired-pulse magnetic
      stimulation studies on the response of the first dorsal interosseous muscle (FDI)
      produced by I1 or I3 waves using our previously reported method which
      preferentially elicits one group of I waves when subjects make a slight voluntary
      contraction. In some experiments the conditioning and test stimuli were
      oppositely directed, in the others they were oriented in the same direction.
      Single motor unit responses were recorded with a concentric needle electrode, and
      surface EMG responses with cup electrodes. 3. In post-stimulus time histograms
      (PSTHs) of the firing probability of motor units, the peaks produced by I3 waves
      were decreased by a subthreshold conditioning stimulus that preferentially
      elicited I1 or I3 waves at an ISI of 4 ms. The amount of decrement depended on
      the intensity of the conditioning stimulus. The stronger the conditioning
      stimulus, the greater the suppression. In contrast, the peaks produced by I1
      waves were little affected by any type of subthreshold conditioning stimulus,
      given 4 ms prior to the test stimulus. At an ISI of 10 ms, a subthreshold
      conditioning stimulus slightly decreased the size of the peak produced by the I3
      waves, but did not affect the peaks evoked by I1 waves. 4. Surface EMGs showed
      that a subthreshold conditioning stimulus suppressed the responses produced by I3
      waves irrespective of its current direction (anterior or posterior). Both the
      amount and duration of suppression depended on the intensity of the conditioning
      stimulus, but not on its current direction. Both parameters increased when the
      intensity increased. At a high intensity conditioning stimulus, suppression was
      evoked at ISIs of 1-20 ms, compatible with the duration of GABA-mediated
      inhibition found in animal experiments. Responses produced by I1 waves were
      little affected by any type of subthreshold conditioning stimulus. 5. We conclude
      that a subthreshold conditioning stimulus given over the motor cortex moderately
      suppresses I3 waves but does not affect I1 waves. The duration of suppression of
      the I3 waves supports the idea that this is an effect of GABAergic inhibition
      within the motor cortex.

PMID- 9575310
TI  - Letter: The correctness of neuropathological diagnoses in clinical practice

PMID- 9575309
TI  - In vivo observations of the intramural arterioles and venules in beating canine
      hearts.
AB  - 1. To evaluate the effects of cardiac contraction on intramyocardial (midwall)
      microvessels, we measured the phasic diameter change of left ventricular
      intramural arterioles and venules using a novel needle-probe videomicroscope with
      a CCD camera and compared it with the diameter change in subepicardial and
      subendocardial vessels. 2. The phasic diameter of the intramural arterioles
      decreased from 130 +/- 79 im in end-diastole to 118 +/- 72 micron (mean +/- S.D.)
      in end-systole by cardiac contraction (10 +/- 6 %, P < 0.001, n = 21). 3. The
      phasic diameter in the intramural venules was almost unchanged from end-diastole
      to end-systole (85 +/- 44 vs. 86 +/- 42 micron, respectively, 2 +/- 6 %, n. s., n
      = 14). 4. Compared with intramural vessels, the diameters of subendocardial
      arterioles and venules decreased by a similar extent (arterioles: 10 +/- 8 %, P <
      0. 001; venules: 12 +/- 10 %, P < 0.001) from end-diastole to end-systole,
      respectively, whereas the diameter of the subepicardial arterioles changed little
      during the cardiac cycle, and subepicardial venule diameter increased by 9 +/- 8
      % (P < 0.01) from end-diastole to end-systole. These findings are consistent with
      our previous report. 5. We suggest that the almost uniform distribution of the
      cardiac contractility effect and arteriolar transmural pressure between the
      subendocardium and the midmyocardium, which together constitute the systolic
      vascular compressive force, accounts for the similarity in the arteriolar
      diameter changes in both myocardial layers. The smaller intravascular pressure
      drop from deep to superficial myocardium relative to the larger intramyocardial
      pressure drop explains the difference in the phasic venular diameter changes
      across the myocardium.

PMID- 9575311
TI  - Intracranial cavernous malformations - natural history and management
AB  - Thirteen papers on different aspects of cerebral cavernomas are reviewed;
      interest in this condition has increased since magnetic resonance imaging (MRI)
      became widely available. The prevalence of cavernomas is uncertain, but they are
      the most common of the angiographically occult vascular malformations. Some are
      isolated occurrences, and some are familial, with a dominant inheritance.
      Screening with MRI of first-degree relatives is justified. The reported annual
      risk of haemorrhage varies widely and is probably between 1 and 3%, with a
      possible increase in risk after a first haemorrhage; the risk may also be higher
      in deep or brain stem cavernomas. Opinions on when surgery should be offered
      vary, with prophylactic surgery not usually recommended. After symptomatic
      haemorrhages, surgery may be more justified for easily accessible lesions. For
      those that are more difficult to approach safely, especially in the brain stem,
      operation is not usually recommended unless there has been at least one
      clinically significant haemorrhage. Epilepsy owing to hemisphere cavernomas can
      often be successfully managed medically, with surgery reserved for intractable
      seizures. In children with epilepsy, there is a stronger argument for surgery.
      Radiosurgery has been used for symptomatic cavernomas that are surgically
      inaccessible. Strong arguments have been advanced both for and against this
      treatment, and the risks probably outweigh the benefits. Suggestions for a
      randomised trial have been made.

PMID- 9575312
TI  - Fibrinolytic agents in the treatment of intraventricular hemorrhage in adults
AB  - This paper aims to review current literature on the treatment of acute
      intraventricular hemorrhage in adults with intraventricular infusion of
      fibrinolytic agents. A literature search on the topics of "intraventricular
      hemorrhage" or "intracerebral hemorrhage" with "thrombolytic therapy",
      "fibrinolytic therapy", "urokinase", "streptokinase", "tissue plasminogen
      activator" or "tPA" covering the years 1966-1997 was carried out electronically.
      This was supplemented by searching the reference lists of the identified
      articles. Articles regarding exclusively intracerebral hemorrhage or hematoma,
      neonatal intraventricular hemorrhage, non-therapeutic issues, and laboratory
      research were excluded. The included articles are summarized in evidence and
      evaluation tables. Six articles evaluating the treatment of intraventricular
      hemorrhage in adults with intraventricular fibrinolytic agents were identified.
      One reports a small randomized clinical trial including 16 patients and appears
      to show a statistically insignificant preference for urokinase treatment. Five
      other reports present case series for which a total of 58 patients were exposed
      to either streptokinase, urokinase, or recombinant tissue plasminogen activator
      (rt-PA) and suggest good outcome. Two of them were with non-randomized
      retrospective or prospective controls, and three have no controls. Despite
      important limitations, all reports suggest that blood is more rapidly cleared
      from the ventricles and outcome is better when administering a fibrinolytic agent
      intraventricularly. While the experience presented in these papers suggests that
      intraventricular administration of fibrinolytic agents may be associated with
      fewer complications, more rapid clearing of blood from the ventricles, less late
      hydrocephalus, and better long-term outcome than is seen in patients treated with
      ventricular drainage alone, it is insufficient to recommend such treatment as a
      matter of policy. Substantial methodologic flaws render these findings suggestive
      at best. If the suggestive findings of these studies were confirmed in well
      designed randomized clinical trials, an important impact on clinical practice
      could be expected.

PMID- 9575313
TI  - Various pathogenetic factors revolving around the central role of protein kinase
      C activation in the occurrence of cerebral vasospasm
AB  - Accumulating evidence indicates that protein kinase C (PKC)-dependent, Ca2+
      independent smooth muscle contraction plays the central role in the occurrence of
      chronic vasospasm following aneurysmal subarachnoid hemorrhage. As far as we
      know, the nitric oxide/ cyclic guanosine monophosphate (cGMP)/protein kinase G
      (PKG) system comprises the most efficacious inhibitory mechanism against the PKC
      dependent contractile mechanism, and the myogenic tonus of normal cerebral
      arteries is thought to be maintained on the balance between these systems. Recent
      studies indicate that in spastic cerebral arteries, the rise in the intracellular
      diacylglycerol level causes PKC activation presumably owing to the overexpression
      of endothelin (ET)-1 as well as the generation of free radicals, whereas the cGMP
      level is inversely reduced owing to the inactivation of soluble guanylate cyclase
      through some as yet unknown mechanism. The resultant loss of balance between the
      two systems is considered to culminate in the occurrence of chronic vasospasm
      lasting for nearly 2 weeks. Based on the above concept, recent papers concerning
      the effects of reactive oxygen species on the arterial smooth muscle, alterations
      of various membrane ion channels, particularly of adenosine triphospate (ATP)
      activated potassium channels in spastic arteries, the preventive effects of ET
      antagonists on vasospasm, and the causative role of ET-1 were reviewed in the
      present article. The roles of the above spasmogenic factors or mechanisms may be
      more clearly understood on the basis of the antagonistic interrelation between
      the PKC and the PKG systems, which exert diverse influences on the force
      generating system as well as on its multifarious regulatory mechanisms in smooth
      muscle cells.

PMID- 9575314
TI  - Recent advances in MR imaging: FLAIR imaging
AB  - Fluid-attenuated inversion recovery (FLAIR) imaging is a technique that increases
      the sensi-tivity of magnetic resonance imaging to detect central nervous system
      (CNS) diseases characterized by an increase in interstitial water con-tent such
      as brain tumors, cerebral infarcts, and gliotic scars. A role for this technique
      in subarchnoid disease processes such as hemorrhage and epidermoid tumor is also
      being revealed.

PMID- 9575315
TI  - Treatment options for spasticity in children
AB  - Partial dorsal root rhizotomy and intrathecal administration of baclofen are two
      modalities used to treat spasticity in children. Each has its own inclusion
      criteria and mechanism of action. Both have been proven to relieve spasticity,
      and both have their particular side effects and complications. Programmable pumps
      for the accurate and reliable administration of intrathecal baclofen are
      expensive and demand a lifelong commitment to medication refill and hardware
      reimplantation. Partial dorsal root rhizotomy is a one-time surgical procedure,
      which differs from one center to another. It requires a team approach for patient
      selection and to determine whether other treatment options should take
      precedence. It also requires a period of postoperative reeducation in the form of
      physiotherapy. While some centers use intraoperative nerve root stimulation and
      muscle response recording as a guidance tool for rootlet sectioning, others claim
      equally good results without the added time-consuming technology.

PMID- 9575316
TI  - Effects of exercise on pregnancy.

PMID- 9575317
TI  - Current immunization recommendations.

PMID- 9575318
TI  - Herpes esophagitis in an immunocompetent host.

PMID- 9575319
TI  - Use of melatonin for insomnia.

PMID- 9575320
TI  - Hyperparathyroidism.
AB  - Hyperparathyroidism is a common cause of hypercalcemia. The hypercalcemia usually
      is discovered during a routine serum chemistry profile. Often, there has been no
      previous suspicion of this disorder. In most patients initially believed to be
      asymptomatic, previously unrecognized symptoms resolve with surgical correction
      of the disorder. The symptoms of hyperparathyroidism are vague and often similar
      to symptoms of depression, irritable bowel syndrome, fibromyalgia or stress
      reaction. Complications of primary hyperparathyroidism include peptic ulcers,
      nephrolithiasis, pancreatitis and dehydration. Surgical management is usually
      indicated. When medical management is used, routine monitoring for clinical
      deterioration is recommended. Preoperative localization of adenomas with
      technetium Tc 99m sestamibi scan is possible but may be unnecessary. An
      experienced surgeon should perform the parathyroidectomy.

PMID- 9575321
TI  - Head and neck manifestations of AIDS in adults.
AB  - Head and neck manifestations of acquired immunodeficiency syndrome (AIDS) are
      among the most common complications of this disease. Some of these manifestations
      are the initial signs of human immunodeficiency virus (HIV) infection, and others
      are associated with full-blown AIDS. Otologic manifestations include otitis
      externa, otitis media, Kaposi's sarcoma and sensorineural hearing loss. Nasal and
      oral manifestations of AIDS are more common than otologic manifestations and
      range from infections, caused by both opportunistic and nonopportunistic
      organisms, to malignancies. We address common manifestations and current
      treatment recommendations.

PMID- 9575322
TI  - Lumbar spine stenosis: a common cause of back and leg pain.
AB  - Lumbar spine stenosis most commonly affects the middle-aged and elderly
      population. Entrapment of the cauda equina roots by hypertrophy of the osseous
      and soft tissue structures surrounding the lumbar spinal canal is often
      associated with incapacitating pain in the back and lower extremities, difficulty
      ambulating, leg paresthesias and weakness and, in severe cases, bowel or bladder
      disturbances. The characteristic syndrome associated with lumbar stenosis is
      termed neurogenic intermittent claudication. This condition must be
      differentiated from true claudication, which is caused by atherosclerosis of the
      pelvofemoral vessels. Although many conditions may be associated with lumbar
      canal stenosis, most cases are idiopathic. Imaging of the lumbar spine performed
      with computed tomography or magnetic resonance imaging often demonstrates
      narrowing of the lumbar canal with compression of the cauda equina nerve roots by
      thickened posterior vertebral elements, facet joints, marginal osteophytes or
      soft tissue structures such as the ligamentum flavum or herniated discs.
      Treatment for symptomatic lumbar stenosis is usually surgical decompression.
      Medical treatment alternatives, such as bed rest, pain management and physical
      therapy, should be reserved for use in debilitated patients or patients whose
      surgical risk is prohibitive as a result of concomitant medical conditions.

PMID- 9575323
TI  - Exercise during pregnancy.
AB  - Exercise has become a vital part of many women's lives. However, theoretic
      concerns have been raised about the safety of some forms of exercise during
      pregnancy. Because of the physiologic changes associated with pregnancy, as well
      as the hemodynamic response to exercise, some precautions should be observed. The
      physician should screen for any contraindications to exercise and encourage
      patients to avoid overly vigorous activity, especially in the third trimester,
      when most pregnant women have a decreased tolerance for weight-bearing exercise.
      Adequate hydration and appropriate ventilation are important in preventing the
      possible teratogenic effects of overheating. Pregnant women should avoid exercise
      that involves the risk of abdominal trauma, falls or excessive joint stress, as
      in contact sports and vigorous racquet sports. In the absence of any obstetric or
      medical complications, most women can maintain a regular exercise regimen during
      pregnancy. Some studies have found a greater sense of well-being, shorter labor
      and fewer obstetric interventions in physically well-conditioned women as
      compared with other women.

PMID- 9575324
TI  - Axillary basal cell carcinoma: a need for full cutaneous examination.
AB  - Basal cell carcinoma is the most common skin malignancy. While this lesion most
      often occurs in sun-exposed areas of the skin, it can also develop in sites that
      are not usually exposed to sunlight or artificial ultraviolet radiation, such as
      the breast, palm or groin. A periodic complete examination of the skin should be
      performed to ensure that atypical presentations of basal cell carcinoma are not
      overlooked or misdiagnosed. Treatment options include curettage and desiccation,
      cryosurgery, surgical excision, radiotherapy and Mohs micrographic surgery.

PMID- 9575325
TI  - Practical steps to smoking cessation for recovering alcoholics.
AB  - Smoking rates among persons with a history of alcohol abuse are triple that of
      the general public. Strong evidence indicates that the risk of cancer and
      cardiovascular disease is higher in recovering alcoholics than in peers who
      smoke, but do not drink alcohol. Yet these persons often receive less than
      optimal tobacco counseling out of fear that attempts at smoking cessation will
      jeopardize their sobriety. Recent research, however, does not support this
      belief; rather, it suggests that smoking cessation may actually enhance alcohol
      abstinence. A model for more effective counseling of smokers in recovery is
      presented, including an algorithm for assessing stages of readiness to change,
      with activities tailored for each stage. Specific motivational counseling
      techniques may be useful in encouraging recovering alcoholics to progress to the
      point that they are ready to change their smoking behavior.

PMID- 9575326
TI  - Use of immunotherapy in a primary care office.
AB  - Immunotherapy has been used for over 80 years. It is a safe and effective
      therapeutic intervention for allergic rhinitis, but its use in the treatment of
      asthma is more controversial. Patients with unstable asthma are at increased risk
      of adverse effects from immunotherapy; therefore, if immunotherapy is used in
      such patients, it should be instituted cautiously. Indications for immunotherapy
      include evidence of IgE-mediated disease and positive results on skin tests or
      radioallergosorbent test (RAST). In addition, before immunotherapy is considered,
      measures to avoid exposure to offending agents and drug therapy should have
      failed to provide relief of symptoms. Before administering immunotherapy in the
      office, physicians should be knowledgeable about the use of immunotherapy and the
      treatment of anaphylaxis, and should have ready access to the equipment needed to
      avert anaphylaxis.

PMID- 9575327
TI  - Preventing congestive heart failure.
AB  - The morbidity, mortality and health care costs associated with congestive heart
      failure make prevention a more attractive public health strategy than treatment.
      Aggressive management of etiologic factors, including hypertension, coronary
      artery disease, valvular disease and excessive alcohol intake, can prevent the
      left ventricular remodeling and dysfunction that lead to heart failure. Early
      intervention with angiotensin converting enzyme inhibitors in patients with
      chronic left ventricular dysfunction can prevent, as well as treat, the syndrome.
      Several intervention strategies in patients with acute myocardial infarction can
      slow or prevent the left ventricular remodeling process that antedates congestive
      heart failure. The primary care physician must be alert to the need for
      aggressive intervention to reduce the burden of heart failure syndrome on the
      patient and on society.

PMID- 9575328
TI  - High-altitude medicine.
AB  - As more people enjoy the outdoors, high-altitude illness is increasingly becoming
      a problem that family physicians across the country must treat. High-altitude
      illness, which usually occurs at altitudes of over 1,500 m (4,921 ft), is caused
      primarily by hypoxia but is compounded by cold and exposure. It presents as one
      of three forms: acute mountain sickness (AMS), high-altitude pulmonary edema
      (HAPE) and high-altitude cerebral edema (HACE). But high-altitude illness can
      have many other manifestations. Cardinal symptoms include dyspnea on exertion and
      at rest, cough, nausea, difficulty sleeping, headache and mental status changes.
      Treatment requires descent, and gradual acclimatization provides the most
      effective prevention. Acetazolimide is an effective preventive aid and can be
      used in certain conditions as treatment.

PMID- 9575329
TI  - CDC releases the 1998 Guidelines for the Treatment of Sexually Transmitted
      Diseases.

PMID- 9575330
TI  - [Immunologic aspects of allergic and non-allergic asthma].
AB  - METHODS: The peripheral blood lymphocytes and lung function have been studied in
      25 patients: 12 affected by atopic asthma and 13 affected by non atopic asthma.
      RESULTS: The results obtained indicate that peripheral blood CD3 and CD4 cell as
      well as HLA-DR marker are higher in the extrinsic asthma group. CONCLUSIONS:
      These findings confirm that an active inflammatory process exists in the group of
      non-atopic and functionally more compromised patients.

PMID- 9575331
TI  - [Validity and reliability of a new questionnaire on patient satisfaction in
      rehabilitative therapy].
AB  - BACKGROUND: The aim of this study was to examine some psychometric properties of
      a new questionnaire measuring patients' satisfaction with respect to the quality
      of care during stay in a rehabilitation unit. The instrument (called SAT-16) is
      composed of 16 four-level items and 2 open-ended questions. The construct
      validity of the 16-item section was already demonstrated in a previous study
      based on factorial analysis. In this study the concurrent validity, further
      aspects of the construct validity and test-retest reliability were analyzed.
      METHODS: The SAT-16 was administered to 339 inpatients, admitted consecutively to
      a Rehabilitation Center. RESULTS: 262 questionnaires (77%) were returned, of
      which 221 with all items filled in. The SAT-16 correlated well with two other
      measures of satisfaction (CSQ-8 and global satisfaction regarding the hospital
      stay). The answers to two open-ended questions came out to be consistent with
      those to the 16 closed-ended questions. The high values for the indices of test
      retest reliability (ICC and kappa) are evidence of the stability of the scores in
      two repeated administrations. CONCLUSIONS: The SAT-16 was found to be provided
      with good psychometric characteristics. It can be proposed as a valid instrument
      for use in clinical practice for the continuous quality improvement of inpatient
      medical rehabilitation programmes.

PMID- 9575332
TI  - [The "age factor" in ovarian cancer. Clinical, therapeutic and prognostic
      aspects].
AB  - 115 patients affected by ovarian tumors, were studied retrospectively, each with
      a follow-up of a minimum of 5 years. These cases were subdivided into two
      subgroups according to the age (younger or older than 65 years) to value the
      differences, from a prognostic and therapeutic point of view about the age of
      neoplasm onset. In patients older than 65 years, there were prevalent cases with
      worse prognosis, linked both to the neoplasm (greater incidence of advanced
      stages at the moment of the diagnosis; prevalence of tumours of low degree of
      differentiation), and to the treatment given (less destroying intervention, with
      a higher frequency of non optimal residual disease; fewer chemotherapeutic cycles
      for every patient, with lower doses and fewer times of administration of drugs;
      higher incidence of phenomena of resistance and rejection of the I line therapy).
      The survival curves were significantly different in the two groups of patients,
      proving a worse prognosis for older women. At last, a multivaried statistical
      analysis, revealed that age, like stage, residual disease and the number of
      chemotherapeutic cycles performed, represent an independent prognostic factor.

PMID- 9575333
TI  - [Components of complement in patients with immediate hypersensitivity].
AB  - BACKGROUND: This prospective study was undertaken to assess the differences
      between the levels of the main plasma components of complement in allergic
      subjects and in those with pseudoallergic clinical manifestations. METHODS:
      Plasma C3 and C4 were evaluated in a total of 256 subjects examined consecutively
      at the allergology outpatients clinic of the Internal Medicine Division B,
      University of Turin. Total IgE and C1-inhibitor levels were also determined in
      128 and 44 subjects respectively. RESULTS: C3 and C4 levels were not
      significantly different (p = 0.398 and p = 0.497) in 123 subjects with a positive
      and 133 with a negative prick test, nor in allergic subjects with respiratory as
      opposed to skin symptoms (p = 0.293 and p = 0.462), whereas the C-1 inhibitor was
      significantly lower (p = 0.046) in the respiratory subgroup. Total IgE was
      positively correlated with the C3 level (p = 0.036) in 75 allergic subjects.
      CONCLUSIONS: These findings suggest that plasma C3 and C4 values are not
      sufficient to discriminate IgE inflammation (positive prick test) and
      pseudoallergy (negative prick test) in the assessment of subjects with clinically
      suspected allergy. The positive correlation between IgE synthesis and C3 also
      points to an interaction between IgE synthesis and C3 regulation proteins in
      patients with IgE mediated diseases. Further investigation of other acute phase
      proteins (C reactive protein, fibrinogen) and the cytokines regulating their
      synthesis (IL-6) in such patients will help to clarify this correlation.

PMID- 9575334
TI  - [Voice pathology in the history of medicine].
AB  - This article, which will be followed by others dealing with the same subject, is
      mainly concerned with the outstanding figures of Ippocrathes of Cos and Galenus
      as far as voice treatment in Greek medicine and under the Roman Empire is
      concerned. But apart from them, many writers and scientists such as Homer,
      Democritus, Plato, Celsius Scribonius Largus, not to mention Plinius, Discorides
      and Martialis dealt with this topic. In addition, the article will briefly deal
      with the ancient Egyptian medicine as well as with the Indian one.

PMID- 9575335
TI  - The mechanism of glutamine-dependent amidotransferases.
AB  - Glutamine-dependent amidotransferases have been known for more than 30 years. The
      mechanism by which these enzymes generate ammonia from the glutamine amide
      nitrogen and transfer it to seven different chemical classes of acceptors has
      been the subject of intense scrutiny for the last 5 years. The increasing number
      of biochemical and structural studies dealing with amidotransferases and with
      mechanistically related enzymes has disclosed the dichotomy of the mechanisms
      within these enzymes for achieving the glutamine amide bond cleavage. Some of
      them use a catalytic Cys/His/Glu triad similar to serine protease, whereas the
      aminoterminal cysteine of the others is believed to play the same function. The
      transfer of ammonia from the glutamine site to the acceptor site which must
      operate in a concerted manner has been demonstrated in two cases to involve
      channelling but is still matter of investigation.

PMID- 9575336
TI  - Enzyme action in glycoprotein synthesis.
AB  - Just a few decades ago, the saccharides bound to glycoproteins were considered
      little more than an irritation. They increased the difficulty of purifying and
      characterizing proteins, making proteins run as several bands on gels and
      smearing them on columns. They were considered a nuisance and were typically
      cleaved away to reveal the 'important part', the protein moiety, for structural
      (e.g. via X-ray crystallography or nuclear magnetic resonance) and functional
      studies. We now realize that that the saccharide is often as important as the
      protein itself, and that glycosylation can have many effects on the function,
      structure, physical properties and targeting of a protein. There are a myriad of
      reviews and books on this subject, reflecting the nearly overwhelming number of
      articles in print discussing saccharide structures, glycoprotein processing
      enzymes and the biological implication of glycosylation. This review discusses,
      in turn, the extent and biological relevance of glycosylation; the structures
      observed; how glycosylated proteins are formed in vivo; the clinical relevance of
      glycosylation, in terms of the correlations between disease states and unusual
      glycosylation patterns; and, finally, the molecules, both natural and synthetic,
      that can be used to study the role of carbohydrates in glycoprotein structure and
      function or to disrupt various carbohydrate recognition processes and enzymatic
      reactions in the glycoprotein synthetic pathway.

PMID- 9575337
TI  - Structure and assembly of the 20S proteasome.
AB  - The barrel-shaped 20S proteasome is one of the two components of a larger 26S
      particle, the multicatalytic 2000-kDa protease complex. The proteolytic sites are
      located in the inner chamber of the 20S particle and are only accessible via
      narrow entrances. This paper reviews the current knowledge concerning proteasome
      formation, proteolytic activities, structural aspects and assembly. Eukaryotic
      proteasomes are made up by four rings each of which contains seven different
      subunits occurring at fixed positions. While the outer rings contain alpha-type
      subunits, the inner ones comprise beta-type subunits. The current assembly model
      for eukaryotic 20S proteasomes is based upon the detection of 13S and 16S
      intermediates, respectively, in addition to previous findings with
      archaebacterial and eubacterial proteasome assembly. The available data suggest a
      cooperative assembly of the alpha-type and beta-type subunits into half
      proteasome-like complexes followed by dimerization into proteasomes. During or
      after dimerization of half proteasomes, the beta-type subunits are processed. The
      prosequence of the beta-type subunits is essential for the assembly proves and
      prevents protease activity of immature proteasomes.

PMID- 9575338
TI  - Activation of cytotoxic T cells by solid tumours?
AB  - Tumour-specific cytotoxic T cells (CTLs) are among the best-defined biological
      anticancer weapons. Nevertheless, they often fail to control tumour growth in
      vivo. Many reasons for this have been evoked: tumours may actively inhibit CTLs,
      or may protect themselves from CTL recognition by various means. However, one
      does not necessarily need to postulate such active immune evasion mechanisms
      specifically acquired by tumour cells. In this review we argue that the failure
      of immune protection is due to the intrinsic inability of tumours to activate an
      effective immune response, and that many tumours are similar to normal tissues in
      this respect. It is striking to see that the majority of the so-called immune
      escape mechanisms are not specifically acquired by selected tumour cells, but are
      common mechanisms shared between solid tumours and normal, healthy tissues.
      Immune responses are poor because tumour antigens do not efficiently localize to
      lymph follicles in lymphoid tissues, and are not efficiently presented to CTLs in
      an immunogenic context. The fact that tumours do not induce CTLs but are often
      susceptible to lymphocyte-mediated cytotoxicity indicates that more intensified
      immunization protocols should result in improved clinical outcome.

PMID- 9575340
TI  - Central IL-1 differentially regulates peripheral IL-6 and TNF synthesis.
AB  - Centrally given interleukin (IL)-1 is known to induce a rapid rises in blood IL
      6. To extend this and to examine the mechanism by which this occurs, the effects
      of intracerebroventricular (i.c.v.) injection of human recombinant IL-1 beta on
      mRNA expression of IL-6 and tumour necrosis factor (TNF) in the spleen and liver
      were examined in rats. I.c.v. injection of IL-1 produced a rapid rise of the
      tissue mRNA levels of Il-6 and TNF in both organs, prior to and/or in parallel
      with an increase in their serum levels. Pretreatment with chlorisondamine, a
      ganglionic blocking agent, inhibited the Il-6 responses, while it had little
      influence on the TNF responses. The results suggest that brain IL-1 induces
      peripheral production of IL-6, but not of TNF, through autonomic nervous system
      activation.

PMID- 9575339
TI  - Stomatal guard cell responses to kinetin and natriuretic peptides are cGMP
      dependent.
AB  - Immunological evidence suggest that plants contain natriuretic peptides (NPs) and
      furthermore (3-[I]iodotyrosol) rat atrial NP (rANP) binds specifically to plant
      membranes. rANP and immunoaffinity-purified plant NP analogues also promote
      concentration-dependent stomatal opening. Here we report that kinetin, a
      synthetic cytokinin, and rANP induce stomatal opening in Tradescantia albiflora
      and that the effect of rANP is critically dependent on the secondary structure of
      the peptide hormone. The native circular molecule is active, whereas the
      linearized molecule shows no biological activity. Furthermore, kinetin- and rANP
      induced stomatal opening is reversibly inhibited by two inhibitors of guanylate
      cyclase, LY 83583 and methylene blue. Stomatal opening is also induced in a
      concentration-dependent manner by the cell-permeant cyclic guanosine-3',5'
      monophosphate (cGMP) analogue 8-Br-cGMP, and this effect is prevented by the
      stomatal closure promoting plant hormone abscisic acid (ABA). We conclude that in
      guard cells kinetin and rANP pathways operate via guanylate cyclase upregulation,
      and we propose that ABA-induced closure is not cGMP-dependent.

PMID- 9575341
TI  - Gonadotrophin-releasing activity of histones H2A and H2B.
AB  - We report that histones H2A and H2B possess gonadotrophin-releasing activity in
      vitro and assess the signal transduction pathways involved in these effects.
      Perifused and incubated rat anterior pituitary (AP) cells were used, and
      luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by
      RIA. Perifusion of cells with histone H2A (30 muM) or histone H2B (30 muM),
      markedly stimulated LH release but failed to elicit any FSH response. Cells
      incubated with 6 or 30 muM histone H2A showed a dose- and time-dependent
      stimulatory effect on bot LH and FSH release which was blocked by 1 muM peptide
      MB35, an 86-120 amino acid fragment of histone H2A. Incubation of pituitary cells
      with gonadotrophin-releasing hormone (GnRH) and histones H2A or H2B showed a
      stimulatory effect on LH and FSH release which was similar to the sum of the
      separate effects. Trifluoperazine as well as ethylene glycol bis(b-aminoethyl
      ether) N,N,N',N'-tetraacetic acid (EGTA), alone or in the presence of the calcium
      ionophore A23187, significantly reduced the response of AP cells to histones.
      Various cyclic adenosine monophosphate (cAMP) enhancers had no effect on histone
      stimulated release of gonadotrophins in incubated AP cells. Our results confirm
      previous evidence that histones may act as hypophysiotrophic signals. Calcium-
      and diacylglycerol-associated pathways, but not cAMP, appear to participate in
      these effects.

PMID- 9575342
TI  - Structure-function correlation and biostability of antibody CDR-derived peptides
      as tumour imaging agents.
AB  - Based on the CDR3 V(H) sequence of a monoclonal antibody (ASM2) raised against
      epithelial cancer cells, the synthetic peptide YCAREPPTRTFAYWG (EPPT1) has been
      found to have an appreciable affinity (Kd = 20 microM) for the deglycosylated
      mucin-derived peptide antigen YVTSAPDTRPAPGST (PDTRP). The technetium
      radiolabelled form of this peptide has been found to be a good tumour-imaging
      candidate for diagnosis of breast carcinoma. Several EPPT1 peptide analogues were
      synthesised. A differential biostability was obtained blocking the end groups of
      EPPT1. The susceptibility to proteolytic degradation was significantly decreased
      for the C-amidated form of EPPT1 than the N-acetylated form. Using resonant
      mirror biosensor technique, the EPPT1 analogues were classified as active and non
      active peptides according to their PDTRP-binding properties. The binding of EPPT1
      to PDTRP in free solution was also determined unambiguously by CD spectroscopy.
      CD spectra of both active and non-active peptides showed the presence of
      irregular conformations in H2) and SDS above cmc. In TFE, significant degree of
      ordered conformations of alpha-helix or beta-turn type were induced but did not
      correlate well with their binding properties. In SDS below cmc a conformational
      difference was observed between the active and non-active peptides. The active
      peptides exhibited CD spectra of aggregation of beta-strand type whilst the non
      active showed CD spectra similar to those in H2O and SDS above cmc, critical
      micelle concentration. A good correlation between the extended conformation of
      beta-strand type and the binding affinity of the active peptides suggests this
      conformation as the binding feature of the EPPT tumour-imaging peptides. These
      information are vital for the design of novel EPPT analogues. Any modification to
      improve binding affinity must retain the ability of the peptides to adopt the
      extended conformation of beta-strand type.

PMID- 9575343
TI  - Binding pockets on the surface of human leukocyte elastase and human leukocyte
      cathepsin G. Implications to the design of inhibitors derived from human C
      reactive protein.
AB  - Analogs of the peptide Val-Thr-Val-Ala-Pro-Val-His-Ile, derived from the primary
      sequence of the acute phase reactant CRP, i.e. amino acid residues 89-96, were
      optimized to inhibit the enzymatic activities of human leukocyte elastase (hLE)
      and human leukocyte cathepsin G (hCG), which are associated with tissue damage
      occurring in the course of several chronic inflammatory conditions. hLE's major
      S1 pocket, lined mostly by hydrophobic amino acid residues, was shown by
      theoretical electrostatic potential calculations to possess some negative charge.
      This pocket was found to be extremely sensitive towards modifications in the P1
      position of CRP derived inhibitors, with valine being the preferred amino acid.
      In contrast, the corresponding S1 pocket of hCG is large and accepts the
      positively charged 'aromatic' side chain of histidine, which increases most
      significantly the capability of CRP derived inhibitors. A prominent positive
      pocket was observed in the distant S7 region of hLE, which is generated by two
      exposed positive residues, Arg177 and Arg217, on the enzymes surface. This long
      range subsite was utilized to increase the hLE inhibitory activity of CRP derived
      peptide using the natural sequence of CRP, which contains a unique glutamic acid
      moiety in the P7 position. In contrast to the charged nature of hLE's S7 pocket,
      the corresponding pocket on the surface of hCG appears to be less prominent.
      Additional hydrophobic N-terminus modifications of CRP89-96 increased the
      inhibitory activity towards both enzymes, provided that residues P1 and p7, were
      designed according to the individual preferences of hLE and hCG. The unique
      interaction between the negative amino acid side chain of CRP with the positive
      S7 pocket of hLE as elucidated in this study, and additional subsite preferences
      may now be used in the design of novel therapeutic substances.

PMID- 9575344
TI  - Effect of serum amyloid A, HDL-apolipoprotein, on endothelial cell proliferation.
      Implication of an enigmatic protein to atherosclerosis.
AB  - The possible contribution of apo-HDL serum amyloid A (SAA) to the protective
      effect of HDL against atherosclerosis was studied by evaluating its effect on
      bovine aortic endothelial cell (BAEC) proliferation. Our results suggest that
      human SAA, both purified and recombinant, in concentrations relevant to mild
      acute phase events, significantly inhibit endothelial cell proliferation in a
      dose-dependent manner (e.g., 50 micrograms/ml causes approximately 88%
      inhibition; p < 0.001). This inhibition was attenuated by addition of fibroblast
      growth factor (FGF), which antagonized the SAA-mediated effect. As levels of TNF
      may be highly elevated during the acute phase response, its effect on BAEC
      proliferation was evaluated and found, at concentrations of > 1 pg/ml, to be
      substantially inhibitory Co-incubation of cells with both SAA and TNF was
      inhibitory, albeit neither additive nor synergistic. FGF antagonized the effect
      of both proteins. Amyloidic deposit (AA, i.e. SAA 1-76), derived from
      pathological proteolysis of SAA, practically retains the inhibitory activity
      (e.g. 50 micrograms/ml causes approximately 66% inhibition; p < 0.001) but
      apparently lacks the regulatory site towards FGF. In contrast to the above
      inhibitory effect, synthetic SAA-related peptide corresponding to the sequence 29
      33 of SAA enhances BAEC proliferation (50 micrograms/ml causes approximately 64%
      increase; p < 0.001). The present data, coupled with our previous observations in
      which SAA was found to induce endothelial PGI2 formation and to inhibit
      overproduction of PGI2 by TNF and LPS as well as platelet aggregation, may
      suggest that SAA contributes to the protective effect of HDL against
      atherosclerosis. This, by means of its modulatory effect on endothelial cell and
      platelet activation, primarily in the presence of other regulatory proteins. SAA
      derived peptides may, potentially, be used as therapeutic agents in the treatment
      of atherosclerosis and cardiovascular diseases.

PMID- 9575345
TI  - Binding kinetics and bioassay of RRE mRNA fragments to a peptide containing the
      recognition domain of HIV-1 Rev.
AB  - Surface plasmon resonance techniques have been used to examine the kinetics of
      binding for two RNA fragments to an RNA binding domain of HIV-1 REv. RBE3 RNA
      elicited an apparent dissociation constant (KD) of 121 nM while RREIIB41-79 RNA
      exhibited an apparent dissociation constant (KD) of 2.5 nM. The dissociation
      rates for both RNA fragments were comparable. However, the shorter sequence,
      RBE3, exhibited considerably slower association kinetics. A series of known
      inhibitors were assayed against these RNA' and the derived K1's were consistent
      with those reported in the literature, validating the method for routine
      inhibitor assays.

PMID- 9575346
TI  - Solid phase synthesis and biological activity of rat relaxin.
AB  - The peptide hormone relaxin was isolated in good yield from the ovaries of the
      pregnant rodent Rattus rattus using a simplified purification schedule. It was
      subjected to comprehensive chemical characterization to confirm both its purity
      and predicted composition. The peptide was also chemically synthesized by the
      solid phase procedure. The two chains comprising the hormone were each assembled
      by the Boc-polystyrene method and, following conventional purification, combined
      in solution to form the single intramolecular and two intermolecular disulfide
      bonds. Following purification, the synthetic rat relaxin was fully chemically
      characterized and shown to be indistinguishable from the native peptide including
      by secondary structure analysis using circular dichroism spectroscopy. The native
      and synthetic rat relaxins were shown to be equally biologically active in the in
      vitro rat uterine relaxation assay and had pEC50 values that were comparable to
      synthetic human H2 relaxin.

PMID- 9575347
TI  - Identification of a mouse orthologue of the human ras-GAP-SH3-domain binding
      protein and structural confirmation that these proteins contain an RNA
      recognition motif.
AB  - Human ras-GTPase-activating protein (GAP120) SH3-domain-binding protein (G3BP)
      has recently been identified on the basis of its specific binding to the GAP120
      SH3 binding domain. Here we report the identification of a mouse G3BP cDNA and
      the confirmation by three dimensional modelling of an RNA recognition motif (RRM)
      in the encoded protein. Mouse G3BP also contains an RGG domain, an acid-rich
      amino acid domain, and several SH3 domain-binding consensus sequences, indicating
      that mammalian G3BPs represent a new family of signal transduction proteins which
      connect tyrosine kinase-linked receptors to cellular RNA metabolism.

PMID- 9575348
TI  - In vitro and in vivo comparison of a randomly coupled antibody fragment-enzyme
      conjugate with a site-specific conjugate.
AB  - Two antibody fragment-enzyme conjugates, one obtained by random coupling of the
      two protein component, the other by site-specific ligation of the same component,
      were compared in vitro and in vivo for their usefulness in antibody directed
      enzyme prodrug therapy (ADEPT). The in vitro studies have shown that the site
      specific conjugate has a higher antigen binding capacity, while both conjugates
      had similar specific enzymic activities. In vivo, the site-specific conjugate was
      cleared more rapidly. When correction was made for this faster clearance, both
      conjugates showed similar antitumor efficacy in a mouse xenograft system upon
      administration of a prodrug.

PMID- 9575349
TI  - Synthesis, purification and biological activity of (Ser10-phosphatidyl)
      urodilatin (phosphourodilatin).
AB  - Based on the global phosphorylation approach, a selective synthesis of (Ser10
      phosphatidyl)-urodilatin (phosphourodilatin), which contains 32 amino acid
      residues and a disulfide loop is described. The peptide was assembled stepwise on
      a polyethyleneglycol-polystyrene support using Fmoc-chemistry. The
      phosphorylation was performed on-resin by phosphitylation with a large excess of
      di-tert-butyl-N,N-diethylphosphoramidite within 1 hour, followed by oxidation
      with tert-butylhydroperoxide to the protected phosphopeptide. After cleavage and
      deprotection the disulfide bridge was introduced without side reactions by iodine
      titration of the mono-acetamidomethyl protected crude peptide. During the
      synthetic pathway, the acylation with side chain-unprotected Fmoc-serine and the
      phosphitylation satisfactorily yielded the expected intermediates. In some
      phosphorylation experiments a by-product having a reduced mass corresponding to
      the H-phosphonate was observed. Illustrated with the synthesis of
      phosphourodilatin, this type of by-product, which could not be separated by HPLC,
      and the difficult amino acid sequence make the synthesis of a large
      phosphopeptide a more delicate task than the synthesis of short phosphopeptides,
      which do not contain oxidation-sensitive amino acids, difficult sequences or
      additional structural elements such as disulfide loops. The biological activity
      of phosphourodilatin was compared with non-phosphorylated urodilatin in two assay
      systems. Both peptides revealed a vasorelaxant effect on aortic smooth muscle
      strips and induced a cGMP-generation in RFL-6 cells with increasing dose
      dependency.

PMID- 9575350
TI  - Modulation of prostaglandin I2 production from bovine aortic endothelial cells by
      serum amyloid A and its N-terminal tetradecapeptide.
AB  - The study was aimed to explore the possible involvement of the acute phase HDL
      apolipoprotein, serum amyloid A (SAA) in the regulation of PGI2 production by
      endothelial cells. This, in view of the recent detection of SAA mRNA in
      endothelial cells of human atherosclerotic lesions. Human SAA induces PGI2
      formation in bovine aortic endothelial cells culture in a concentration relevant
      to moderate acute phase events. 50 micrograms/ml of purified human SAA increases
      PGI2 production from a mean basal level of 2,490 +/- 330 pg/ml by 1.80 +/- 0.1
      fold (n = 10; p < 0.01). The PGI2 inducing activity resides apparently in the N
      terminal, i.e. amino acid residues 1-14, of the SAA molecule, 50 micrograms/ml of
      the peptide induces 2.9 +/- 0.5 fold increase of PGI2 production (n = 4; p <
      0.03). TNF and LPS each induce PGI2 production in a concentration and time
      dependent manner. TNF in concentration of 10 ng/ml induces, in the presence of
      calf serum, an increase of 24.9 +/- 2.3 fold (n = 4; p < 0.001) and LPS in
      concentration of 1 microgram/ml causes a 18.3 +/- 1.3 fold increase, (n = 4; p <
      0.01). In serum-free cultures, only a 2.5 +/- 0.3 fold increase was detected by
      10 ng/ml TNF (n = 4), and a 5.9 +/- 0.4 by 1 microgram/ml of LPS. Thus, serum has
      a strong effect on PGI2 induction. When 50 micrograms/ml SAA is coadministered
      with 1 ng/ml TNF it reduces the TNF-induction of PGI2 from 7.7 +/- 2.8 to 3.3 +/-
      1.2 fold (n = 4; p < 0.01). SAA attenuates, as well, LPS-mediated activity,
      although in a less pronounced manner. Our finding suggest a potential
      physiological function for SAA in regulation of basal and cytokine-induced PGI2
      production by vascular endothelium. The capacity of SAA to markedly moderate PGI2
      induction by TNF and LPS suggest that it may play a role in defending against
      vessel damage, in cases of atherosclerosis, bacterial infection or septic shock.
      The induction of PGI2 by SAA through its N-terminal domain, which also exhibits
      an anti-platelet aggregation activity, suggests a potential therapeutical use for
      this peptide as an anti-hypertensive and an anti-aggregatory agent.

PMID- 9575352
TI  - The search for inhibitors of interleukin-1 based on the sequence of interleukin-1
      receptor antagonist.
AB  - In order to find the low-molecular-weight interleukin-1 (IL-1) inhibitors, we
      synthesised a series of peptides, derived from three regions of interleukin-1
      receptor antagonist (IL-1ra): N-terminal (residues 5-9), central (90-98) and C
      terminal (143-148). The decision was based on the thorough analysis of structural
      and functional properties of IL-1 proteins and the resemblance of some fragments
      of IL-1ra to well-known immunomodulators, like thymopentin and tuftsin. The
      competition between our peptides and IL-1 were measured as the inhibition of IL-1
      induced IL-2 production in LBRM/CTLL cell line system. All peptides presented
      some activity, although the most interesting results (when the range of activity
      and dose-dependence were taken into account) were obtained for tuftsin and
      peptide VTKFYF from the C-terminal part of IL-1ra.

PMID- 9575351
TI  - Triple helical DNA.

PMID- 9575353
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1995). I.
      Susceptibility distribution].
AB  - The frequencies of isolation and susceptibilities to antimicrobial agents were
      investigated on 704 bacterial strains isolated from patients with urinary tract
      infections (UTIs) in 11 hospitals during the period of June 1995 to May 1996. Of
      the above bacterial isolates, Gram-positive bacteria accounted for 29.8% and a
      majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for
      70.2% and most of them were Escherichia coli. Susceptibilities of several
      isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus
      faecalis Ampicillin (ABPC) and imipenem (IPM) showed the highest activities
      against E. faecalis isolated from patients with UTIs. The MIC90S of them were 1
      microgram/ml. Vancomycin (VCM) and piperacillin (PIPC) were also active with the
      MIC90S of 2 micrograms/ml and 4 micrograms/ml, respectively. The others had low
      activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus
      including MRSA VCM showed the highest activities against S. aureus isolated from
      patients with UTIs. Its MIC90 was 1 microgram/ml against both S. aureus and MRSA.
      Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The other
      except minocycline (MINO) had very low activities with the MIC90S of 64
      micrograms/ml or above. 3. Staphylococcus epidermidis ABK and MINO showed the
      strongest activities against S. epidermidis isolated from patients with UTIs. The
      MIC90S of them were 0.25 microgram/ml. VCM was also active with the MIC90 of 1
      microgram/ml. The MIC90S of cephems ranged from 2 micrograms/ml to 16
      micrograms/ml in 1994, but they ranged from 8 micrograms/ml to 128 micrograms/ml
      in 1995. These results indicated that some resistances existed among S.
      epidermidis to cephems. 4. Streptococcus agalactiae All drugs except gentamicin
      (GM) were active against S. agalactiae. ABPC, cefmenoxime (CMX), IPM,
      erythromycin (EM), clindamycin (CLDM) and clarithromycin (CAM) showed the highest
      activities. The MICs for all strains were lower than 0.125 microgram/ml. The
      MIC90S of the others were 2 micrograms/ml or below. 5. Citrobacter freundii IPM
      showed the highest activity against C. freundii isolated from patients UTIs. Its
      MIC90 was 1 microgram/ml. GM was also active with the MIC90 of 2 micrograms/ml.
      Cefpirome (CPR), cefozopran (CZOP) and amikacin (AMK) were also active with the
      MIC90S of 4 micrograms/ml. Penicillins and cephems except CMX, CPR and CZOP
      showed low activities with MIC90S of 256 micrograms/ml or above. 6. Enterobacter
      cloacae IPM showed the highest activity against E. cloacae. The MICs for all
      strains were equal to or lower than 1 microgram/ml. MINO and tosufloxacin (TFLX)
      were also active with the MIC90S of 8 micrograms/ml. Penicillins and cephems
      except CPR and CZOP showed lower activities with the MIC90S of 256 micrograms/ml
      or above. 7. Escherichia coli. Most of the antimicrobial agents were active
      against E. coli. Particularly CPR, CZOP and IPM showed the highest activities
      against E. coli. The MICs for all strains were equal to or lower than 0.5
      microgram/ml. CMX and TFLX were also active with the MIC90S of 0.125 microgram/ml
      or below. Penicillins were slightly active with MIC90S of 128 micrograms/ml or
      above. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except
      penicillins, with MIC90S of 2 micrograms/ml or below. Carumonam (CRMN) had the
      strongest activity against K. pneumoniae, the MICs for all strains were equal to
      or lower than 0.125 microgram/ml. Comparing with the result of 1994, the
      sensitivities of K. pneumoniae against all drugs had obviously changed into a
      better state. For example, the MIC90S of cephems ranged from 0.25 microgram/ml to
      16 micrograms/ml in 1994, but they were all lower than 2 micrograms/ml in 1995.
      9. Proteus mirabilis P. mirabilis was susceptible to a majority of drugs. CMX,
      ceftazidime (CAZ), cefixime (CFIX), and CRMN showed the highest activities
      against P. mirabilis isolated from patients with UTIs. MICs of CRMN for all

PMID- 9575354
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1995). II.
      Background of patients].
AB  - Clinical background was investigated on patients with urinary tract infections
      (UTIs) from whom 785 bacterial strains were isolated in 11 hospitals during the
      period from June, 1995 through May, 1996. 1. Distributions of age and sex of
      patients and type of infections. Among the patients examined, those with ages 50
      years or older were the most frequent (males: 80.5%, females: 69.7%), and, among
      females, those with ages in the 20's were 12.6%. With regard to types of
      infections, more than a half of infections among males were of complicated types,
      but most of infections among females were of uncomplicated types, especially
      among females of ages less than 60 years. 2. Ages of patients and types of
      pathogens. The higher the ages of patients, the lesser became the isolation
      frequencies of Proteus spp. and Serratia spp., but the higher were those of
      Klebsiella spp. and Pseudomonas spp. 3. Effect of antibiotic use on isolation
      frequencies of pathogens. Use of antibiotics decreased pathogens isolated from
      patients with uncomplicated UTIs drastically (237 isolates before antibiotics
      compared to 33 after). Even isolated pathogens from patients with complicated
      UTIs decreased drastically with the use of antibiotics when indwelling catheters
      were not in use (200 isolates before antibiotics compared to 83 after), but when
      indwelling catheters were in use, antibiotics apparently failed to decrease the
      isolation frequency. 4. Surgical procedures and types of causative organisms for
      UTIs. Escherichia coli was the most frequently isolated organism from
      uncomplicated cases of UTIs. From cases of complicated UTIs without indwelling
      catheters, Enterococcus faecalis was the most frequently isolated, followed by E.
      coli, P. aeruginosa and Klebsiella spp. When a surgical procedures were not done,
      E. coli was isolated most frequently. From cases of complicated UTIs with
      indwelling catheters, P. aeruginosa, E. faecalis and S. aureus were the organisms
      that were mainly isolated, with isolation frequencies of 23.9%, 17.3% and 12.7%,
      respectively. When no surgical procedures were used, isolation frequencies of P.
      aeruginosa, Klebsiella spp. and E. faecalis were 25.7%, 14.3% and 14.3%,
      respectively.

PMID- 9575355
TI  - [Clinical evaluation of a new macrolide antibiotic, azithromycin, in the
      pediatric field].
AB  - Azithromycin (AZM) preparations in fine granules and capsules were evaluated in
      36 pediatric patients with various infections. In patients with pneumonia caused
      by Moraxella catarrhalis, Haemophilus influenzae or Mycoplasma pneumoniae,
      bronchitis, pharyngitis, scarlet fever, whooping cough, or campylobacter
      enteritis, AZM was found effective in 94.4% (34/36). As for the bacteriological
      efficacy of AZM, all of 12 strains identified were found eradicated by the
      treatment. Plasma T 1/2(24 approximately 48 hrs.) of AZM in fine granules, given
      two patients at 10 mg/kg body weight once daily for 3 days, were 41.5 and 51.4
      hours, while AUC0 approximately infinity was 7.45 and 13.44 mg.hr/ml. The rates
      of AZM recovered in the urine samples from two pediatrics patients in the first
      81 hours of treatment, when it is given in fine granules at 10 mg/kg body weight
      once daily for 3 days, were 6.27% and 11.0%. Data from 43 patients were included
      for drug safety evaluation. Neither adverse reactions nor abnormal laboratory
      changes were observed. In conclusion, AZM was found useful in treatment of
      pediatric infections.

PMID- 9575356
TI  - Overview: functional implications of the design of skeletal muscles.

PMID- 9575357
TI  - Estimation of active force-length characteristics of human vastus lateralis
      muscle.
AB  - The length and angles of fascicles were determined for the vastus lateralis
      muscle (VL) using ultrasonography in 6 subjects performing ramp isometric knee
      extension. The subject increased torque from zero (relax) to maximum (MVC) with
      the knee positioned every 15 degrees, from 10 degrees to 100 degrees flexion (0
      degrees = full extension). As the knee was positioned closer to extension,
      fascicle length was shorter [116 +/- 4.7 (mean +/- SEM) mm at 100 degrees vs. 88
      +/- 4.1 mm at 10 degrees (relax)]. The fascicle length of the VL decreased with
      increasing torque at each knee position [116 +/- 4.7 (relax) to 92 +/- 4.3 mm
      (MVC) at 100 degrees]. On the other hand, fascicle angles increased with an
      increase in torque. These changes reflected the compliance of the muscle-tendon
      complex which increased as the knee reached a straight position. The estimated
      muscle force of the VL was maximal (2,052 +/- 125 N) for a fascicle length of 78
      +/- 2.7 mm (i.e. optimum length) with the knee positioned at 70 degrees of
      flexion. The relationship between muscle force and fascicle length indicated that
      the VL uses the ascending (knee < 70 degrees), plateau (70 degrees), and
      descending regions (> 70 degrees) of the force-length curve.

PMID- 9575358
TI  - Muscle fiber length and moment arm coordination during dorsi- and plantarflexion
      in the mouse hindlimb.
AB  - The purpose of this study was to test the hypothesis that muscle fiber length and
      joint moment arm are combined in such a way that maximum muscle force is produced
      during locomotion. Plantarflexor (soleus, SOL and medial gastrocnemius, MG) and
      dorsiflexor (extensor digitorum longus, EDL and tibialis anterior, TA) muscle
      architecture in the mouse was measured along with their associated moment arms.
      Fiber length varied significantly between muscles ranging from 5.7 +/- 0.2 mm
      (MG) to 7.6 +/- 0.2 mm (TA). Plantarflexor moment arms were over twice as large
      as dorsiflexor moment arms (1.88 +/- 0.06 mm vs. 0.84 +/- 0.03 mm) suggesting a
      greater muscle length change with joint angle for plantarflexors compared to
      dorsiflexors. Using a simple muscle-joint model, the active sarcomere length
      range in these muscle groups was calculated and proved to be quite similar
      between functional groups. The active range for dorsiflexors was 2.2-2.4 microns,
      while the active range for plantarflexors was 2.2-2.5 microns, indicating that
      both muscle groups operate primarily near the plateau of their length tension
      relation. Finally, when calculating force produced by muscles during locomotion,
      the combination of moment arm and fiber length measured in all muscle groups
      yielded muscle-joint systems that produced near maximal forces at the velocities
      modeled. These data indicate that fiber length and moment arm appear to be
      coordinated to yield the greatest possible force production during locomotion.

PMID- 9575359
TI  - Effects of muscle length on the response to unloading.
AB  - Muscle mass, distribution of fiber types, fiber cross-sectional areas (CSA) and
      selected enzyme activities were determined in rats hindlimb-suspended free of
      immobilization (Susp-Free), suspended with the ankle dorsiflexed (Susp-DF, soleus
      stretched) or plantarflexed (Susp-PF, soleus shortened) for 10 days and compared
      to cage-control (Con) rats. Reduction of muscle weight associated with suspension
      was prevented in Susp-DF rats. The mean CSAs of slow fibers were Con = Susp-DF >
      Susp > PF > Susp-Free and of fast and intermediate fiber tended to be Susp-DF >
      Con > Susp-PF = Susp-Free. Mean activities of succinate dehydrogenase (SDH),
      alpha-glycerophosphate dehydrogenase (GPD) and myofibrillar adenosine
      triphosphatase (mATPase) in slow and fast fibers were similar in Con and Susp
      Free rats. Mean SDH activity in slow fibers was higher in Susp-DF and Susp-PF
      than in Con and Susp-Free. No significant differences in SDH activities of fast
      fibers were observed among groups. GPD activity was higher in slow fibers of Susp
      DF and Susp-PF compared to Con. The mATPase activity was higher in slow fibers of
      Susp-DF compared to Con and Susp-Free rats and lower in fast fibers of Susp-DF
      compared to Con rats. Thus, when compared to control, the patterns of adaptation
      were more similar in the Susp-DF and Susp-PF than in the Susp-Free. Although
      these results are consistent with previous studies demonstrating that the load
      placed on a muscle can affect protein metabolism, the direction and magnitude of
      the adaptive responses observed in the present study were closely associated with
      the chronically imposed changes in muscle length, i.e. fixed at either a
      shortened or a lengthened position.

PMID- 9575360
TI  - Functional morphology of serially linked skeletal muscle fibers.
AB  - In the skeletal muscle fiber organization of many vertebrate muscles, serial
      arrangements or linkages of muscle fibers along the muscle or fascicle are
      commonly found. These serially linked muscle fibers employ distinct junctional
      morphologies from muscle to muscle. Notable are the end-to-end linkages of muscle
      fibers through tendinous intersections (TIs), where many fibers end onto a
      continuous connective tissue plate with folded terminations similar to
      myotendinous junctions. Besides this end-to-end linkage, overlapping linkages or
      arrangements occur among nonspanning fibers terminating intrafascicularly. These
      nonspanning fibers bear tapering terminations with direct cell-cell (myomuscular)
      junctions or without any specialized junctions. Despite their overlapping
      linkages or tapering profiles, nonspanning fibers maintain a uniform sarcomere
      length along the linked fibers, suggesting that the overlapping-linked
      nonspanning fibers are equivalent to the end-to-end linked fibers in their
      mechanical capacity. However, the junctional compliance could differ in their
      extracellular elastic components and their organization at junctional sites,
      e.g., direct mechanical (myomuscular) junctions vs. indirect linkages through
      connective tissue. Increasing evidence suggests that the elastic components,
      including muscle fibers as well as connective tissues, are more critical than
      previously thought for the mode and/or the efficiency of tension transmission
      among serially arranged fibers and thus for the mechanical properties of the
      muscle.

PMID- 9575361
TI  - Appearance of complex branched muscle fibers is associated with a shift to slow
      muscle characteristics.
AB  - To examine the effects of numerous complex branched fibers (CBF) on whole muscle
      contractile properties, we established a model of myopathic muscles containing a
      large number of CBF by repeated local injection of bupivacaine hydrochloride
      (Marcaine) into the plantaris (PLA) muscle. Marcaine injections were administered
      once weekly for 10 weeks into the right PLA muscles of Wistar male rats. The in
      situ contractile properties of Marcaine-injected PLA muscles (I-PLA) were
      examined under urethane anesthesia, and compared with the contralateral (control)
      PLA muscle (C-PLA). Numerical and morphological examination using the modified
      nitric acid fiber digestion method and scanning electron microscopy showed that
      Marcaine resulted in an 8-fold increase in the number of branched fibers in the I
      PLA muscles and about 70% of these fibers were CBF. The latter were composed of
      ten or more muscle fibers fused together along with many thin and thick, long and
      short daughter branches. The time to peak tension of twitch and tetanus, and 1/2
      relaxation time were significantly longer in I-PLA muscles, representing a shift
      to slow muscle characteristics. However, the total area of slow fibers/muscle
      cross-sectional area was similar in I-PLA and C-PLA muscles. Aggregates of same
      type fibers (slow fibers) with small and large diameters were observed,
      reflecting an expected cross-sectional property of CBF. Our results suggest that
      the appearance of several CBF in a muscle is associated with a shift towards
      slower contractile properties in the affected muscle.

PMID- 9575362
TI  - Spindle representation relative to distribution of muscle fiber types in the cat
      capsularis muscle.
AB  - The spatial representation of muscle spindles (Sps) in the small (approximately
      0.2 g), simply structured capsularis muscle that crosses anterior to the cat's
      hip joint was compared with the distribution of the slow oxidative (SO) and few
      (< 10%) fast oxidative-glycolytic (FOG) fibers of which it is composed to see if
      their distributions were consistent with a hypothesis that sensory input from Sps
      influences the incidence of extrafusal fiber types. In frozen sections from 4
      muscles, FOG fibers were enumerated along 1-mm strips across the muscle's maximum
      width, and between the 'superficial' surface and the 'deep' one that contacts the
      joint. The locations of Sps in complete serial sections of 2 paraffin-embedded
      muscles, one perfused with the hip joint flexed and the other with it extended,
      were plotted on an outline of each muscle at its midlength, and their numbers and
      density in horizontal and sagittal 'strata' determined. In general, the incidence
      of Sps increased down the superficial-to-deep axis, while FOG fibers became
      fewer, as is consistent with support of SO status by Sp input. Along the
      craniocaudal axis, i.e. width, the numbers of FOG fibers rose toward the hip
      joint, but this was not associated with a monomodal gradient of Sps. In the
      extended muscle, however, the lengths of the axial bundle and capsular space of
      Sps in the half of the muscle next to the joint exceeded those in the longer,
      cranial half, implying that under stretch the input from Sps became higher toward
      the joint. In the non-extended muscle these lengths did not differ, although the
      lengths of extrafusal fibers isolated from 2 macerated muscles and normalized
      according to sarcomere length decreased linearily by approximately 50% along
      craniocaudal axis. It is explained that if elastic resistance of a Sp's sensory
      region exceeded that of an equivalent length of septal tissue in-series, the
      progressive shift in the ratio of compliances across this trapezoidally-shaped
      muscle should result in relatively greater lengthening of Sps at the shorter
      border as the muscle was extended. Levels of discharge conducive to transition of
      some motor units to the FOG type might be attained. Thus, gradients in the
      discharge of Sps (but not necessarily incidence) along both transverse and
      superficial-to-deep axes may be consistent with Sp sensory input influencing the
      distribution of at least these types of motor units.

PMID- 9575363
TI  - Architecture and the division of labor in the extensor carpi radialis muscle of
      horses.
AB  - The extensor carpi radialis muscle of the horse is deceptive at first appearance.
      It has a fusiform shape similar to other forearm extensor muscles. The fiber
      arrangement also appears long and relatively parallel. However, it may contain
      two or more compartments that correlate with differing functional roles.
      Histochemical and immunocytochemical analysis of proximal and distal regions of
      the muscle (n = 9) demonstrate that the proximal portion of the muscle is
      composed of a mean of 13% type I, presumed slow twitch, and 61% type IIb,
      presumed fast twitch fibers. In contrast, the distal compartment is composed of a
      mean of about 43% type I and only 22% type IIB fibers. The type I and IIa fibers
      are all highly aerobic based on nicotinamide dinucleotide tetrazolium reductase
      reactions. Correlative data regarding the myosin isoforms has been obtained with
      4% SDS-PAGE analysis of myosin heavy chain isoforms which demonstrate isoforms
      migrating at rates similar to rat type I, IIa, and IIx. The latter has been
      referred to as type IIB/X in a study of the horse's gluteus medius muscle. We
      propose that the in-series 'compartmentalization' of the muscle, while not
      conforming strictly to the definitions of neuromuscular compartments, relates to
      the insertion of the lacertus fibrosus, a distal slip of the biceps brachii, upon
      the extensor carpi radialis. Earlier studies demonstrated a high proportion of
      type I fibers in the equine lateral biceps brachii which were thought to
      stabilize the shoulder during long periods of quiet standing. Because of action
      imposed on the distal compartment by the biceps brachii, slow and fatigue
      resistant functions are part of the limb's passive stay apparatus to effect long
      term standing by the horse. Thus, the fatigue-resistant compartments of biceps
      brachii and extensor carpi radialis may constitute an in-series arrangement of
      the two muscles. The proximal compartment is suited to provide powerful, more
      fatigable contractions during locomotion and likely affects stress or strain
      within the distal postural compartment.

PMID- 9575364
TI  - Architectural and histochemical properties of cat hip 'cuff' muscles.
AB  - The architectural properties and fiber-type composition of the cat hip 'cuff'
      muscles, i.e. the deep layer of muscles encircling the hip joint, were
      determined. The muscles studied included the gluteus minimus, obturator internus
      and externus, gemellus superior and inferior, pyriformis, quadratus femoris and
      capsularis. In addition, the fiber-type composition was determined for the
      iliacus muscle. Compared to other lower limb muscles, the cuff muscles were small
      (approximately 0.2 to 2.7 g) and short (approximately 15 to 40 mm long) and had
      short mean fiber lengths (approximately 7 to 12 mm long), small angles of fiber
      pinnation (< or = 12 degrees), and small physiological cross-sectional areas
      (approximately 0.2 to 2.8 cm2). The percentage of the cross-sectional area
      comprised of slow fibers ranged from 24 to 95% with this value being over 50% in
      5/9 muscles studied. The small angle of pinnation and short fiber lengths
      optimize force production and the relatively high percentage of slow fibers
      suggest a high level of activation. Both of these properties are consistent with
      a hip stabilization role for these muscles. In addition, the high percentage of
      slow fibers suggests a high spindle density and a possible role of these muscles
      in providing proprioceptive feedback to the central nervous system for the
      control of posture and locomotion.

PMID- 9575365
TI  - Skeletal muscle architecture and fiber-type distribution with the multiple
      bellies of the mouse extensor digitorum longus muscle.
AB  - The purpose of this study was to describe the extent to which architectural and
      fiber-type characteristics of the four bellies of the mouse extensor digitorum
      longus (EDL) suggest specialization of the digits, and to mathematically model
      the functional effects of the structural properties. Six mice were perfused in
      situ with glutaraldehyde while the lower limb was positioned approximately in the
      neutral position. After perfusion, lower limbs were removed and placed in
      glutaraldehyde until the EDL was dissected from the limb and separated into
      individual muscle bellies corresponding to each digit for architectural
      determination. The results showed that the muscle belly of digit 5 tended to be
      different from the muscle bellies of digits 2-4 for many architectural
      characteristics. Muscle mass, physiological cross-sectional area, muscle length,
      and fiber length were all significantly greater in digit 5. Proximal tendon
      length was also significantly longer in digit 5, and distal tendon length, as
      well as total tendon length, were significantly shorter in digit 5. Sarcomere
      length was shortest at the proximal end of the muscle and longest, 60-80%, toward
      the distal end. Fiber type distribution was about 60% FOG, 39% FG with only 1% SO
      fibers in all muscle bellies. Muscle-tendon modeling illustrated that peak force
      and maximal shortening velocity were greatest in digit 5. Inclusion of the tendon
      in the model resulted in a 10% shift of the force-length curve to longer lengths.
      Assuming muscle structure is matched to function, we speculate that digit 5 of
      the mouse EDL bears higher loads over a greater excursion during locomotion
      compared to the remaining digits.

PMID- 9575366
TI  - Perineal muscles and their innervation: metabolic and functional significance of
      the motor unit.
AB  - Cross-sectional areas and succinate dehydrogenase (SDH) activities of muscle
      fibers in the rat levator ani (LA) and bulbocavernosus (BC) were determined and
      compared with those of the soleus (SOL) and superficial (TAs) and deep (TAd)
      portions of the tibialis anterior (TA). In addition, cell body sizes and SDH
      activities of spinal motoneurons innervating the LA and BC were examined.
      Histochemical myofibrillar adenosine triphosphatase (mATPase) staining reactions
      following alkaline and acid preincubations revealed that all the muscle fibers in
      the LA and BC were type IIB. Gel electrophoresis, however, showed that the LA and
      BC contained 2.9 and 2.4% type IIx myosin heavy chain (MHC) isoform,
      respectively. Immunohistochemical analyses using MHC antibodies showed that the
      muscle fibers in the LA and BC had types IIx / IIa (approximately 3%) or type IIb
      MHC isoforms. The mean fiber cross-sectional areas in the LA and BC were
      significantly smaller than those in the SOL, TAs, or TAd. The mean fiber SDH
      activities in the LA and BC were significantly lower than those in the SOL or
      TAd, and similar to TAs. The population of alpha motoneurons innervating the LA
      and BC had similar SDH activities, irrespective of their cell body sizes. These
      data indicate that the LA and BC are comprised of a relatively homogeneous
      population of small, fast and low oxidative fibers innervated by a relatively
      homogeneous population of spinal motoneurons. These characteristics of the muscle
      fibers and motoneurons are consistent with their function in short, high
      intensity activities.

PMID- 9575367
TI  - Primary thymic epithelial neoplasms: current concepts and controversies.

PMID- 9575368
TI  - Nomenclature of chronic hepatitis: the new look.
AB  - The new recommendations for nomenclature, grading, and staging of chronic
      hepatitis and related biliary and other disorders are attempts to standardize the
      criteria and simplify the terminology used in making these diagnoses. It is hoped
      that an emphasis on the etiology as part of the diagnosis will eliminate the
      previous association with poor prognosis that was implied with a diagnosis of
      CAH. The inclusion of a system of grading and staging, whether it is numerical or
      descriptive, simple or complex, matters less than the need for it to communicate
      important information about the degree of necroinflammatory activity (grade) and
      the extent of the disease (stage of fibrosis) that are likely factors of
      prognostic and therapeutic significance.

PMID- 9575369
TI  - Prognostic indicators in breast cancer and who needs them.
AB  - In the prognosis of breast cancer, pathologists are facing a time of
      consolidation. Widely accepted guidelines have been gained only recently, with
      expectations that further developments are soon to come. Prognostic data
      influence systemic treatment decisions that are largely dependent on stage
      criteria of lymph nodes and tumor size as well as menopausal status. Some
      researchers propose that lymph node removal has no therapeutic consequences and
      may not be necessary if the majority of women are to be treated by chemotherapy.
      Some pathologists take this information as gospel for simplifying the management
      of a complex disease, whereas others take information available at different
      levels of certainty and set treatment threshold probabilities on an individual
      patient basis. With regard to invasive carcinoma and systemic therapy, I believe
      that combined histologic grade, including an emphasis on mitotic counts and other
      proliferation indicators, provides information at either end of the staging
      spectrum. Thus, high-grade, small tumors are likely to recur and low-grade, large
      tumors are unlikely to recur, at least within a 2- to 5-year period. Whether use
      of this information can be extended and verified for use in therapeutic decision
      making for neoadjuvant chemotherapy or various escalated chemotherapy regimens
      remains to be established. However, this use of prognostic indicators or
      predictors to indicate therapeutic responsiveness represents the field's
      immediate future. There are separate and important indicators of local treatment
      failure in the breast following conservation. It is likely that the extensiveness
      of DCIS is the major determinant of local recurrence and that its interaction
      with extensiveness, type of carcinoma in situ, and the branching ductal anatomy
      of the breast are of primary importance. Finally, the groups of conditions
      recognized as DCIS continue to provide a fertile field of questioning and
      discovery. Unassailable at the present time is the evidence that small, low-grade
      lesions may be treated effectively by planned wide local excision. Precise
      guidelines and further information are necessary from planned trials stratified
      by size and histologic criteria. Prognostic considerations have only become
      important in guiding treatment decisions in the past few decades. The escalating
      importance of prognostic categories derives from the availability of more varied
      treatment options, which have applications in the different clinical settings
      discussed in this chapter.

PMID- 9575370
TI  - Uterine pathology in tamoxifen-treated patients with breast cancer.
AB  - In the last 20 years, tamoxifen has become the drug of choice in the treatment of
      breast carcinoma in both advanced and early stages. Furthermore, the ability of
      tamoxifen to prevent mammary carcinoma in the contralateral breast has prompted
      the creation of trials that include healthy patients with an increased risk of
      developing breast cancer with the purpose of verifying the drug's prophylactic
      action. As a consequence, a large number of healthy women or women with a long
      life expectancy are being treated with tamoxifen for long periods, making it
      crucial to study the possible long-term effects associated with this therapy. A
      weak estrogen-like effect of tamoxifen on the endometrium has been documented.
      This is supported by the increased incidence of glandular hyperplasia, polyps,
      carcinoma, and sarcoma in tamoxifen-treated patients. Some studies have shown
      that not all endometrial carcinomas arising in tamoxifen-treated patients have
      the favorable histologic and prognostic features typical of estrogen-associated
      endometrial cancers. This, in conjunction with the demonstrated carcinogenicity
      of tamoxifen in some animal models, indicates the need for caution in the use of
      this drug and makes strict gynecologic surveillance of tamoxifen-treated patients
      imperative.

PMID- 9575371
TI  - A symposium on controversies in the pathology of transitional cell carcinomas of
      the urinary bladder, Part II.

PMID- 9575372
TI  - Benign mimics of prostatic adenocarcinoma on needle biopsy.
AB  - Various benign processes can mimic prostatic adenocarcinoma on needle biopsy.
      These processes include glandular lesions such as adenosis, atrophy, VMGH, and
      BCH; inflammatory conditions such as acute and chronic or granulomatous
      prostatitis; and the effects of therapy such as external beam radiation or
      androgen deprivation. Normal benign prostate tissues including seminal vesicles,
      paraganglia, and ganglion cells may also be confused histologically with
      prostatic adenocarcinoma in needle biopsy specimens. With careful attention to
      architectural and cytologic features, these lesions can be readily distinguished
      from prostatic adenocarcinoma in most cases. In difficult cases,
      immunohistochemical studies using antibodies to PSA and high molecular weight
      cytokeratin (34 beta E12) have proved to be an invaluable adjunct in the
      differential diagnosis of prostatic adenocarcinoma on needle biopsy.

PMID- 9575373
TI  - Drug-induced vascular lesions of the liver.

PMID- 9575374
TI  - Malignant mesothelioma in women.
AB  - About 8% of our cases of mesothelioma occur in women, with a median age of 59
      years. Our percentage is lower than other series reported in the literature
      because of the large number of occupationally exposed men referred to our
      laboratory. Tumor arose in the pleura in 86% of the women in our study, and the
      majority were epithelial. Pleural plaques were found in half of the women for
      which this information was available, and asbestosis was found in only 16%. A
      history of exposure to asbestos was identified in three quarters of the women,
      more than half of whom were household contacts of asbestos workers. Occupational
      exposure to asbestos was identified in only 19% of patients. An elevated tissue
      asbestos burden was noted in 70% of women from whom lung tissue was available for
      analysis. The main fiber type identified was amosite, followed by tremolite and
      chrysotile. These findings and those from other countries suggest a need for
      reassessment of the background rate of mesothelioma in industrialized nations.

PMID- 9575375
TI  - The role of fine-needle aspiration cytology and core biopsy in the diagnosis of
      proliferative and atypical breast lesions.

PMID- 9575376
TI  - Pseudomyxoma peritonei: new concepts in diagnosis, origin, nomenclature, and
      relationship to mucinous borderline (low malignant potential) tumors of the
      ovary.
AB  - For many years the clinical syndrome of PMP has been enigmatic. Based on recent
      studies reevaluating the condition, tumors previously designated PMP can now be
      viewed as two pathologically and prognostically distinct disease processes.
      Disseminated peritoneal adenomucinosis is characterized by copious mucinous
      ascites (the classical clinical syndrome of PMP) and histologically bland
      peritoneal mucinous tumors. The condition can be attributed to a ruptured
      appendiceal mucinous adenoma in the vast majority of cases. It has an indolent
      clinical course when surgically treated but may recur over months to years.
      Peritoneal mucinous carcinomatosis is characterized by abundant peritoneal
      mucinous tumor, similar to the clinical presentation of adenomucinosis. However,
      microscopically, the peritoneal tumors have the architectural and cytologic
      features of carcinoma, are derived from gastrointestinal mucinous
      adenocarcinomas, and are associated with a significantly worse prognosis than
      cases of adenomucinosis. A third group of tumors displays intermediate or
      discordant histologic features but manifests a clinical course very similar to
      cases of pure peritoneal carcinomatosis. Women often have concomitant ovarian
      mucinous tumors that suggest primary ovarian neoplasia. Morphologic,
      immunohistochemical, and molecular studies support the interpretation that the
      ovarian tumors are secondary and that adenomucinosis is of appendiceal origin in
      women as well as men. The recognition that the ovarian tumors in nearly all of
      the cases of DPAM and mucinous carcinomatosis are secondary seriously calls into
      question the existence of a borderline group of ovarian mucinous tumors.
      Therefore, primary ovarian mucinous tumors should be classified as either benign
      or malignant. Tumors exhibiting the features currently interpreted as borderline
      should be included in the benign group and designated atypical proliferative
      mucinous tumors.

PMID- 9575377
TI  - Introduction to molecular oncology.

PMID- 9575378
TI  - Subdivisions of auditory cortex and levels of processing in primates.
AB  - In a series of experiments on New World and Old World monkeys, architectonic
      features of auditory cortex were related to tone frequency maps and patterns of
      connections to generate and evaluate theories of cortical organization. The
      results suggest that cortical processing of auditory information involves a
      number of functionally distinct fields that can be broadly grouped into four or
      more levels of processing. At the first level, there are three primary-like
      areas, each with a discrete pattern of tonotopic organization, koniocortical
      histological features, and direct inputs from the ventral division of the medial
      geniculate complex. These three core areas are interconnected and project to a
      narrow surrounding belt of perhaps seven areas which receive thalamic input from
      the major divisions of the medial geniculate complex, the
      suprageniculate/limitans complex, and the medial pulvinar. The belt areas connect
      with a lateral parabelt region of two or more fields that are almost devoid of
      direct connections with the core and the ventral division of the medial
      geniculate complex. The parabelt fields connect with more distant cortex in the
      superior temporal gyrus, superior temporal sulcus, and prefrontal cortex. The
      results indicate that auditory processing involves 15 or more cortical areas,
      each of which is interconnected with a number of other fields, especially
      adjoining fields of the same level.

PMID- 9575379
TI  - Parallel processing in the auditory cortex of primates.
AB  - Evidence from anatomical tracer studies as well as lesions of the primary
      auditory cortex (AI) indicate that the principal relay nucleus of the auditory
      thalamus, the ventral part of the medial geniculate (MGv), projects in parallel
      to AI and the rostral area on the supratemporal plane of the macaque monkey. The
      caudomedial area, by contrast, receives input from MGv only indirectly via AI,
      and neurons in this area are often tuned to the spatial location of a complex
      sound. The belt areas on the lateral surface of the superior temporal gyrus
      receive input from the primary areas. Neurons in these areas respond better to
      more complex stimuli, such as band-pass noise pulses of frequency-modulated
      sweeps, than to pure tones. Often neurons in the lateral belt respond well to
      species-specific communication calls. The hypothesis is put forward that the
      central auditory pathways in the macaque monkey are organized into parallel
      streams, similar to the visual system, one for the processing of spatial
      information, the other for the processing of auditory "patterns". Evidence from
      neuroimaging studies in humans with MRI and PET are consistent with this
      hypothesis. Virtual auditory space stimuli lead to selective activation of an
      inferior parietal region, whereas speech-like stimuli activate superior temporal
      regions.

PMID- 9575380
TI  - Spatial distribution of responses to simple and complex sounds in the primary
      auditory cortex.
AB  - The basic functional organization of the cat primary auditory cortex is discussed
      as it is revealed by electrophysiological studies of the distribution of
      elementary receptive field (RF) parameters. RFs of cortical neurons have been
      shown to vary considerably from neuron to neuron; additionally, specific RF
      properties vary independently. Furthermore, some of the RF properties are
      nonhomogeneously distributed across the auditory cortex and can be interpreted as
      forming "maps" that represent specific stimulus information in a topographic way.
      Accordingly, the functional organization of the primary auditory cortex is
      interpreted as a series of superimposed independent parameter maps. The
      consequences of such a layout for the spatial and temporal coding of pure tones
      and speech sounds is illustrated and ramifications for the interpretation of far
      field event-related potentials are discussed.

PMID- 9575381
TI  - Neuronal responses across cortical field A1 in plasticity induced by peripheral
      auditory organ damage.
AB  - The adult auditory cortex is capable of a plastic reorganization of its tonotopic
      map after damage to restricted parts of the cochlear sensory epithelium. We
      examine the precise conditions of cochlear damage required to demonstrate such
      plasticity in the primary auditory cortex (A1) of the cat and the changes
      observed in neuronal responses in the A1 which has reorganized in plasticity of
      the tonotopic map. From these data we attempt to predict the conditions required
      for similar plasticity to occur in humans after cochlear damage.

PMID- 9575382
TI  - Learning-induced physiological memory in adult primary auditory cortex: receptive
      fields plasticity, model, and mechanisms.
AB  - It is well established that the functional organization of adult sensory
      cortices, including the auditory cortex, can be modified by deafferentation,
      sensory deprivation, or selective sensory stimulation. This paper reviews
      evidence establishing that the adult primary auditory cortex develops
      physiological plasticity during learning. Determination of frequency receptive
      fields before and at various times following aversive classical conditioning and
      instrumental avoidance learning in the guinea pig reveals increased neuronal
      responses to the pure tone frequency used as a conditioned stimulus (CS). In
      contrast, responses to the pretraining best frequency and other non-CS
      frequencies are decreased. These opposite changes are often sufficient to shift
      cellular tuning toward or even to the frequency of the CS. Learning-induced
      receptive field (RF) plasticity (i) is associative (requires pairing tone and
      shock), (ii) highly specific to the CS frequency (e.g., limited to this frequency
      +/- a small fraction of an octave), (iii) discriminative (specific increased
      response to a reinforced CS+ frequency but decreased response to a nonreinforced
      CS- frequency), (iv) develops extremely rapidly (within 5 trials, the fewest
      trials tested), and (v) is retained indefinitely (tested to 8 weeks). Moreover,
      RF plasticity is robust and not due to arousal, but can be expressed in the
      deeply anesthetized subject. Because learning- induced RF plasticity has the
      major characteristics of associative memory, it is therefore referred to as
      "physiological memory". We developed a model of RF plasticity based on
      convergence in the auditory cortex of nucleus basalis cholinergic effects acting
      at muscarinic receptors, with lemniscal and nonlemniscal frequency information
      from the ventral and magnocellular divisions of the medial geniculate nucleus,
      respectively. In the model, the specificity of RF plasticity is dependent on
      Hebbian rules of covariance. This aspect was confirmed in vivo using
      microstimulation techniques. Further, the model predicts that pairing a tone with
      activation of the nucleus basalis is sufficient to induce RF plasticity similar
      to that obtained in behavioral learning. This prediction has been confirmed.
      Additional tests of the model are described. RF plasticity is thought to
      translate the acquired significance of sound into an increased frequency
      representation of behaviorally important stimuli.

PMID- 9575383
TI  - Speech sound representation, perception, and plasticity: a neurophysiologic
      perceptive.
AB  - Historically, auditory research has focused predominately upon how relatively
      simple acoustic signals are represented in the neuronal responses of the auditory
      periphery. However, in order to understand the neurophysiology underlying speech
      perception, the ultimate objective is to discover how speech sounds are
      represented in the central auditory system and to relate that representation to
      the perception of speech as a meaningful acoustic signal. This paper reviews
      three areas that pertain to the central auditory representation of speech: (1)
      the differences in neural representation of speech sounds at different levels of
      the auditory system; (2) the relation between the representation of sound in the
      auditory pathway and the perception/misperception of speech, and (3) the training
      related plasticity of speech sound neural representation and speech perception.

PMID- 9575384
TI  - Study of the human auditory cortices using a whole-head magnetometer: left vs.
      right hemisphere and ipsilateral vs. contralateral stimulation.
AB  - Structural and functional asymmetries of the temporal lobe affect language
      development and may also play a role in a variety of disorders, ranging from
      specific language impairment to schizophrenia. Whole-head neuromagnetometers
      allow the noninvasive measurement of functional asymmetries since activity from
      both hemispheres is recorded simultaneously. In the present study, the location
      of the auditory cortices and their responsiveness to pure tones was compared
      between hemispheres in healthy human subjects. Data suggest a greater
      contralateral than ipsilateral activation. In line with previous findings,
      sources of responses for the right hemisphere seem to be more anterior than for
      the left one.

PMID- 9575385
TI  - High-precision neuromagnetic study of the functional organization of the human
      auditory cortex.
AB  - Previous studies have proven that a dipole source analysis of the auditory evoked
      field is capable of providing evidence of the tonotopic organization of the human
      auditory cortex. To explore the nature of the estimated dipoles in greater
      detail, a single subject was extensively studied, and the estimated sources were
      registered in a three-dimensional reconstruction of the cortical surface derived
      from magnetic resonance images. The stimuli were 500-ms tone bursts with
      frequencies of 250, 500, 1,000, and 2,000 Hz (mean intensity of 60 dB SL). The
      total number of stimuli presented per condition was about 3,600 (36 independent
      experiments spread over 4 days). Using special postprocessing techniques, the
      relative localization accuracy could be enhanced to such an extent that
      differences in the dipole locations of 1 mm could be clearly distinguished. The
      results suggest that peak N1m (latency around 100 ms) arises from the planum
      temporale, whereas peak P2m (latency around 170 ms) appears to correspond to a
      center of activity in (or close to) Heschl's gyrus. The tonotopic organization
      found for the generator of N1m was consistent with earlier studies ("the higher
      the frequency the deeper the source"). However, additional findings (time
      dependence of the estimated sources; slightly different tonotopy obtained for
      field change; dependence of the estimated sources on the estimation technique)
      indicate that multiple areas are involved in the generation of N1m. Evidence of a
      frequency-dependent source location was found also for P2m.

PMID- 9575386
TI  - Optical imaging of intrinsic signals in chinchilla auditory cortex.
AB  - We have assessed sound frequency and intensity responses in primary auditory
      cortex of the (ketamine) anesthetized chinchilla using optical imaging of
      intrinsic signals. Temporal cortex was exposed via a 10-mm craniotomy and a
      windowed chamber was mounted. A 4-second period of gated tones (10 ms rise/fall;
      50 ms plateau; 10/s) was presented to the contralateral ear at levels between 0
      and 80 dB SPL. The cortical surface was illuminated with 540 nm light and video
      images captured in 0.5-second bins for 7.5 s (Imager 2001; Optical Imaging).
      Intrinsic signals were first apparent 0.5-1 s after stimulus onset, and were
      maximal after 3-4 s; they decayed over several seconds. The cortical area in
      which intrinsic activity was detected corresponded closely with
      electrophysiologically defined AI cortex. Intrinsic signals can reliably be
      detected to stimuli at 30-40 dB SPL, and in general, the area of intrinsic signal
      activity tends to expand with increasing stimulation level. Using stimulation
      levels of 80 dB SPL, we show that low-frequency stimuli (0.5-1 kHz) evoke
      intrinsic signals in anterior areas whilst posterior areas are activated by high
      frequency stimuli (e.g. 16 kHz). Thus a low- to high-frequency tonotopic
      organization is seen along this axis.

PMID- 9575387
TI  - Coping and appraisal of daily stressors predict heart rate and blood pressure
      levels in young women.
AB  - An anger-provocation paradigm was used to assess the effects of coping processes
      and appraisal of daily stressors on stress reactivity in 33 normotensive
      undergraduate women. Participants performed a mental arithmetic and an
      interpersonal conflict task during the pre- and postmenstrual phases of their
      menstrual cycles. Increased use of the emotion-focused coping processes of
      tension reduction and positive reappraisal was correlated with lower levels of
      baseline heart rate, whereas distancing was associated with higher levels of
      systolic blood pressure reactivity during the conflict task. Perceiving daily
      stressors as more stressful was associated with higher baseline diastolic blood
      pressure levels. The authors concluded that the transactional model of stress is
      useful for generating hypotheses about factors that predict heart rate and blood
      pressure levels in women.

PMID- 9575388
TI  - LEIPAD, an internationally applicable instrument to assess quality of life in the
      elderly.
AB  - A questionnaire to assess quality of life in the elderly was developed under the
      auspices of the European office of the World Health Organization. Stages in
      construction of the instrument, which was designed for international application,
      particularly at the primary level, are described. The latest version of the
      questionnaire is composed of 49 self-assessment item, 31 of which can be grouped
      into 7 subscales: Physical Function, Self-Care, Depression and Anxiety, Cognitive
      Functioning, Sexual Functioning, and Life Satisfaction. The remaining 18 items
      serve as moderators for assessing the influence of social desirability factors
      and personality characteristics on the individual scores for the 7 core
      instrument subscales. The questionnaire has been administered to 586 individuals
      aged 65 years and over recruited in communities in Italy (Padua and Brescia), the
      Netherlands (Leiden), and Finland (Helsinki). The main psychometric
      characteristics of the instrument, together with its concurrent validity with the
      Rotterdam Questionnaire, are illustrated.

PMID- 9575389
TI  - Coping with pain produced by physical activity in persons with chronic low back
      pain: immediate assessment following a specific pain event.
AB  - Coping with chronic pain during exposure to pain produced by activity was
      examined in 30 patients with chronic low back pain referred to a university pain
      management center. Patients' range of motion, autonomic responses, and
      anticipatory anxiety ratings before exposure and ratings of pain and anxiety
      after exposure were assessed, and the number of repetitions of the activities
      that produced the pain was recorded. Analyses showed that using coping self
      statement was associated with lower skin conductance during anticipation and
      greater range of motion. Praying, hoping, and catastrophizing were associated
      with greater anticipatory anxiety, greater anxiety during the painful activity,
      and less range of motion from the onset of increased pain to the point of pain
      tolerance. Praying and hoping were associated with higher pain ratings and fewer
      repetitions of the activity. Assessment of coping during an incident of pain and
      multiple methods to measure pain and distress provided convincing evidence that
      patients' self-management responses influence the consequences of pain exposure.

PMID- 9575390
TI  - Adherence to a prophylactic medication regimen in patients with symptomatic
      versus asymptomatic ischemic heart disease.
AB  - Although angina pectoris is the most common symptom of coronary artery disease,
      some patients do not experience angina during ischemic episodes. The effects of
      asymptomatic (silent) heart disease on patient self-management have rarely been
      studied. Studies of other patient populations with asymptomatic illnesses
      indicate that patients with silent myocardial ischemia might adhere less well to
      a prophylactic medication regimen than would those with symptomatic ischemia.
      Depression, a state associated with poor adherence to medical regimens is more
      common among patients with symptomatic ischemia. For prevention of thromboembolic
      events, 37 patients with documented ischemic heart disease who denied having
      anginal symptoms and 28 patients who reported almost daily symptoms were given a
      3-week supply of low-dose aspirin packaged in an unobtrusive electronic adherence
      monitor. All other medications were provided in standard pill bottles. The
      symptomatic patients removed their prescribed aspirin on 62.4% of the days; the
      patients with silent ischemia took their medication on 77.3% of the days.
      Possible explanations for these results, their clinical implications, and
      directions for future research are discussed.

PMID- 9575391
TI  - Self-reported coping behavior in health and disease: assessment with a card sort
      game.
AB  - The authors tested the hypothesis that individuals with a variety of severe
      chronic illnesses and the healthy elderly exhibit a loss of flexibility in their
      response to a variety of stressors, compared with healthy adults. A card sort
      game designed to assess self-reported coping behavior under different stressful
      life situations was used to compare healthy adults with individuals with multiple
      sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and the elderly.
      The healthy adults were found to exhibit more variability than any of the illness
      groups or the elderly. Healthy function is marked by a complex type of
      variability.

PMID- 9575392
TI  - Outcome of coronary artery bypass surgery in diabetic transplant candidates.
AB  - Insulin-dependent diabetic (IDDM) patients with end-stage renal disease and
      coronary artery stenoses > or = 75% have a poor prognosis. However, information
      is lacking on the morbidity and mortality of the coronary artery bypass operation
      in this group. We studied 30 consecutive IDDM transplant candidates undergoing a
      bypass operation to determine the incidence of complications and long-term
      outcome. Perioperative mortality was 3% and the complication rate was 60%. During
      follow-up, five patients experienced six myocardial infarctions, the majority
      within six months of operation. Twenty-one patients underwent successful kidney
      transplantation after the bypass operation. Overall patient survival was 80%,
      73%, and 66% at 1, 2 and 4 yr. In summary, the coronary artery bypass procedure
      in IDDM transplant candidates has a high morbidity, but the long-term outcome is
      good. Appropriately counseled IDDM transplant candidates with coronary artery
      disease should be considered for coronary revascularization and subsequent
      transplantation.

PMID- 9575393
TI  - Experience of ABO-incompatible living kidney transplantation after double
      filtration plasmapheresis.
AB  - We achieved success in ABO-incompatible renal allografting after removing anti-A
      and/or anti-B antibodies from the recipient's plasma using double filtration
      plasmapheresis (DFPP). We report here the results of our initial 2 cases. Case 1
      was a 40-yr-old female whose blood group was A+. The donor was her younger
      brother, a 37-yr-old male, whose blood group was B+. The human lymphocyte
      antigens (HLAs) were one haplotype identical, and the stimulation index of the
      mixed lymphocyte culture (MLC-SI) was 34. Case 2 was a 28-yr-old male whose blood
      group was B+. The donor was his father, a 58-yr-old male, whose blood group was
      AB+. The HLAs were one-haplo-type identical as well, and the MLC-SI was 71. We
      carried out 4 sessions of DFPP pre-operatively; i.e. on days -6, -4, -2 and -1.
      2.5 1 of plasma were treated with 500 ml of 4.4% plasma protein fraction in each
      procedure. The pre-operative target titer of anti-A/B antibody, measured by the
      saline tube test, was set at less than x 8. We also used 5 kinds of
      immunosuppressants. Cyclosporine was administered on day -2 beginning with 8
      mg/kg/d, and its dose was modified according to the trough level. 500 mg of
      methylprednisolone were administered intravenously during the operation, and
      prednisolone was started on day 1 with 60 mg/d and tapered. Azathioprine was
      started on day -2 with 2 mg/kg/d for 7 d and 1 mg/kg/d thereafter. 5 mg/kg/d of
      gusperimus was given intravenously from day 0 for 5 d. 30 mg/kg/d of ALG was
      given intravenously from day 0 for 14 d. Along with these immunosuppressants, 0.1
      mg/kg/h of nafamostat mesilate was administered intravenously from day 0 for 3 d,
      and 4 mg/kg/d of ticlopidine was given orally from day 3. X-Ray irradiation to
      the renal graft was not done. Following splenectomy standard renal allografting
      was performed. In Case 1, the titer of anti-B antibody was reduced from x 16 to x
      4. In Case 2, the titer of anti-A antibody was reduced from x 32 to x 4. The post
      operative courses of these 2 cases were satisfactory. Although our experience is
      limited, ABO incompatible kidney transplantation can safely be performed using
      DFPP.

PMID- 9575394
TI  - Risk factors in bone marrow transplant recipients with leukaemia. Increased
      relapse risk in patients treated with ciprofloxacin for gut decontamination.
AB  - Three hundred and six patients with low- and intermediate-risk leukaemias
      undergoing allogeneic BMT between 1980 and March 1996 were studied regarding
      transplantation-related mortality (TRM), relapse, and leukaemia-free survival
      (LFS). Among the patients were 262 recipients of marrow from HLA-identical
      siblings and 44 patients receiving marrow from HLA-A, -B, and -DR identical
      unrelated donors. Between 1986 and 1993, 153 adult patients received
      ciprofloxacin continuously during Cy conditioning, but since November 1993
      ciprofloxacin has not been given until after Cy treatment. TRM at 5 yr showed an
      incidence of 30%. Significant risk factors in Cox regression multivariate
      analysis comprised acute GVHD grades II-IV (p < 0.0001), seropositivity for 3-4
      herpes viruses prior to BMT (p = 0.002), intermediate risk disease (p = 0.008),
      female donor to male recipient (p = 0.015), and a donor age over 17 yr (p =
      0.025). The risk of relapse was studied from 90 d after BMT, and the overall 5-yr
      incidence was 32%. Significant risk factors comprised acute leukaemia, as
      compared to CML (p = 0.003), total body irradiation (TBI) compared to busulphan
      treatment (p = 0.011), gram-negative prophylaxis with ciprofloxacin during
      cyclophosphamide (Cy) conditioning (p = 0.024), GVHD prophylaxis using a
      combination of methotrexate (MTX) and cyclosporine (CSA), compared to monotherapy
      (p = 0.037) and absence of chronic GVHD (p = 0.050). The 5-yr probability of
      relapse in patients receiving ciprofloxacin prophylaxis during Cy conditioning
      was 40%, compared to 24% in patients not receiving this treatment (p = 0.01).
      Overall, LFS at 5 yr was 49%. LFS was evaluated from day 30 after BMT until
      relapse or death of the patient. We found no difference in TRM, relapse or LFS
      between recipients of HLA-identical sibling or unrelated bone marrow, risk
      factors significantly associated with an inferior LFS included acute GVHD grades
      II-IV (p = 0.0002), intermediate risk disease (p = 0.003), donor seropositivity
      for 3-4 herpes viruses (p = 0.046), and TBI conditioning (p = 0.048).

PMID- 9575395
TI  - Assessment of function and survival as measures of renal graft outcome following
      kidney and kidney-pancreas transplantation in type I diabetics.
AB  - Reports on renal graft outcome after kidney-alone (KA) and simultaneous pancreas
      kidney (SPK) transplants have focused on graft survival instead of function. The
      aim of this study is to compare renal graft outcome after KA and SPK using graft
      function and survival as the measures of outcome. The records of 102 transplants
      performed in type I diabetics from 10/90 to 9/96 were reviewed (SPK 42, KA 60).
      Serum creatinine (Cr) and calculated glomerular filtration rate (GFR) were used
      as estimates of graft function. Cr were similar in SPK and KA on day 3 (4.8 +/-
      2.9 vs. 4.8 +/- 2.8 mg/dl, P = 0.9) and day 7 (2.5 +/- 1.8 vs. 3.0 +/- 2.5 mg/dl,
      P = 0.3). GFR was higher KA at 6 months (57 +/- 18 vs. 51 +/- 12 ml/min, P =
      0.08), 1 yr (55 +/- 23 vs. 51 +/- 11 ml/min, P = 0.4) and 3 yr (60 +/- 22 vs. 42
      +/- 16 ml/min, P = 0.03). Kidney graft survival was similar in KA and SPK at 1
      and 5 yr (87% vs. 89% and 44% vs. 47%, P = 0.8). Immunologic failure of the renal
      graft occurred more frequently in SPK (58% vs. 48%, P = 0.04) whereas death with
      function was more common in KA (33% vs. 17%, P = 0.04). In KA, risk factors for
      failure of the renal graft included acute rejection (P = 0.008, relative risk or
      rr = 3.4) and African American recipient (P = 0.06, rr = 2.8). In SPK, risk
      factors included donor age > 40 yr (P = 0.05, rr = 5.3) and African American
      donor (P = 0.03, rr = 4.5). Logistic regression analysis revealed the following
      risk factors for GFR < 50 ml/min at 1 yr: acute rejection (P = 0.03, rr = 2.2)
      and Cr > 3 mg/dl on day 7 (P = 0.06, rr = 2.3). In conclusion, although renal
      graft survival was similar after KA and SPK, better graft function was observed
      in KA at 3 yr. Assessment of renal graft function allows us to evaluate outcome
      from a different perspective than graft survival, and these two measures of
      outcome complement each other.

PMID- 9575396
TI  - Effect of postoperative complications on health and employment following liver
      transplantation.
AB  - The influence of postoperative complications on employment and health status
      following orthotopic liver transplantation (OLT) remains elusive. Postoperative
      complications were scored prospectively using a standardized medical outcome
      classification in each patient transplanted at Duke University from October 1992
      to January 1995. Functional status was evaluated by using the Karnofsky score.
      Between 12 and 18 months following transplantation, patients were asked to
      complete mailed questionnaires to assess employment and health status (SF-36).
      The response rate was 86% (42 of 49 eligible patients). The mean patient age was
      48 yr. Sixteen of 42 patients (38%) exhibited minimal or no postoperative
      complications, and 62% exhibited moderate to severe postoperative complications.
      Age, gender, education, UNOS status for severity of disease, insurance status,
      and Karnofsky score did not correlate with postoperative complications.
      Postoperative complications did not predict employment post-transplantation.
      Paradoxically, patients with minimal or no postoperative complications perceived
      that their health status was significantly impaired post-transplantation, as
      evidenced by a median score of 0 in the role-physical subscale of the SF-36, in
      contrast to those patients with moderate or severe postoperative complications
      who exhibited a median score of 25 (p < 0.01). Similarly, patients with minimal
      or no postoperative complications had significantly lower scores on the mental
      health subscale than those with moderate or severe complications, with median
      score of 60 vs. 78 (p < 0.03). The physical functioning subscale was not affected
      by postoperative complications. Thirteen of 42 (31%) respondents returned to full
      employment post-transplantation. Health perceptions differed with respect to
      employment status post-transplantation. Patients unemployed post-transplantation
      exhibited a median score of 55 in the physical functioning subscale, a value much
      lower than the median score of 80 in the patients who were employed post
      transplantation (p < 0.02). No differences in the role physical or mental health
      subscales were noted with respect to employment status post-transplantation.
      Employment status was unaffected by Karnofsky status, indicating that functional
      status does not predict employment. In conclusion, patients exhibited very poor
      health perceptions post-transplantation, irrespective of postoperative
      complications. Prospective evaluation of patients undergoing liver
      transplantation revealed that medical complications did not affect employment
      post-transplantation.

PMID- 9575398
TI  - Successful treatment of post-transplant lymphoproliferative disorder with
      interferon-alpha and intravenous immunoglobulin.
AB  - We report on the use of interferon-alpha (INF-a) and high-dose non-specific
      intravenous immunoglobulin (IVIg) in 2 patients (a 60-yr-old female and a 65-yr
      old male) who developed post-transplant lymphoproliferative disorder (PTLD) 2 and
      8 months after heart and liver transplantation, respectively. Both patients had
      received immunosuppression with ATG, CsA, azathioprine, and prednisone. The first
      patient did not receive additional immunosuppression with biological agents. The
      second patient developed 3 steroid-resistant acute rejection episodes requiring
      OKT3 (cumulative dose 100 mg) and ATG (cumulative dose 3450 mg). The first
      patient presented with nodules involving the liver, spleen, lungs and nasophar,
      ynx. The second patient presented with subcutaneous and liver nodules, as well as
      pert-portal and para-aortic lymphadenopathies. The histological diagnosis was
      diffuse B-cell PTLD in both patients. Despite reduction of immunosuppression, a
      progression of lesions was observed in both patients over 5 months and 2 months,
      respectively. The first patient received INF-alpha (2 x 10(6) IU, s.c. 3
      times/wk) and IVIg (0.5 g/kg i.v. every 15 d) for.4 months, while the second
      patient received the same therapy for 12 and 7 months, respectively. Complete
      disappearance of all lesions was observed after 3 months of therapy in the first
      patient and after 7 months of therapy in the second patient, as assessed by CT
      scan. PTLD remains in remission 47 and 33 months after therapy, respectively. Our
      preliminary results suggest that the combination of INF-alpha and IVIg can be an
      effective therapy for PTLD which does not respond to reduction of
      immunosuppression.

PMID- 9575397
TI  - Is kidney graft biopsy indicated in recipients with newly developed, microscopic
      hematuria?
AB  - We actively performed renal allograft biopsies on 87 living donor renal
      transplant recipients presenting with stable serum creatinine but showing newly
      developed recurrent microscopic hematuria with a small amount of proteinuria
      during the maintenance phase of immunosuppression and found definite pathological
      lesions in 56 cases (64%). Chronic rejection of a mild grade (n = 27) and various
      kinds of glomerulonephritis (n = 27) were the major pathological diagnoses, and
      from 14 cases singular or complicated cyclosporine (CsA) toxicity was found.
      Twenty-four out of the 27 glomerulonephritis cases were IgA nephropathy, which is
      the most common glomerulonephritis in Korea. Through this study, the authors
      found chronic rejection or glomerulonephritis even in grafts which are generally
      considered to be normal. CsA nephrotoxicity, which was not expected clinically,
      could be found. In summary, renal allograft biopsy on patients, even with stable
      graft function when they start to show microscopic hematuria with or without a
      small amount of proteinuria, should be performed to document the early intragraft
      events if there are no medical contraindications.

PMID- 9575399
TI  - Application of in situ hybridization technique for quantitative assessment of
      ongoing symptomatic Epstein-Barr virus infection after living related liver
      transplantation.
AB  - For quantitative assessment of ongoing symptomatic Epstein-Barr virus (EBV)
      infection in pediatric recipients of liver transplantation, we determined the
      number of peripheral blood mononuclear cells (PBMC) infected by EBV by in situ
      hybridization (ISH) and related the results with clinical courses of those
      patients. Twenty-four patients had symptomatic EBV infection between February
      1995 and March 1996. Blood samples were obtained from these 24 patients at the
      time of acute phase, from 13 of them during convalescence, and 37 pediatric
      patients before transplantation. ISH was performed on the PBMC and polymerase
      chain reaction (PCR) on DNA from whole blood. Oligonucleotide probes for ISH were
      chosen from coding sequences of EBV-encoded small nuclear RNA 1 (EBER1). Results
      of ISH were reported in a number of cells expressing EBER1/5 x 104 PBMC (#EBER1).
      Fever, diarrhea, upper respiratory symptoms, pleural effusion, ascites,
      lymphadenopathy, and lymphoproliferative disease (LPD) accompanied with EBV
      infection proven by serology, viral-specific stain or PCR were regarded as EBV
      related diseases (EBVD). All samples with positive #EBER1 were accompanied by
      positive EBV PCR. #EBERI was 68.2 +/- 144.9 (mean +/- SD) ranging from 0 to 621
      in the acute phase, 0.20 +/- 0.41 ranging from 0 to 2 in the convalescence phase,
      0.27 +/- 0.77 in 23 preoperative patients with positive serology, and 0 in all 14
      preoperative patients with negative serology. The #EBER1 in ongoing EBVD was
      significantly greater than that of patients in convalescence or before
      transplantation. Patients with #EBERI greater than 10 had a significantly lower
      chance of convalescence and a higher mortality than patients with #EBER 1 less
      than 10. We conclude that #EBER1 could be a specific and quantitative marker of
      EBVD and might predict progression to LPD.

PMID- 9575400
TI  - Risk factors for acute renal failure requiring dialysis after liver
      transplantation.
AB  - Acute renal failure (ARF) is a common and severe complication after liver
      transplantation (LT). The aim of this study was to ascertain the impact of ARF
      requiring dialysis in the outcome of LT and to analyze the risk factors leading
      to this event in the early post-operative period. From October 1988 to December
      1994, 172 LT were performed in 158 patients. Postoperative ARF occurred in 88
      transplants (51.1%) during the early postoperative period: mild ARF was found in
      46 (serum creatinine 1.5-3 mg/dl), moderate ARF in 12 (serum creatinine > 3
      mg/dl) and severe ARF in 30 (serum creatinine > 3 mg/dl with dialysis
      requirement). Preoperative, intraoperative, and postoperative variables were
      studied, comparing patients presenting severe ARF with the remaining patients.
      Postoperative mortality in the dialysed group was much higher than in the non
      dialysis group (50% vs. 13.4%)(p < 0.001) and 1-yr actuarial graft survival was
      73.4% for the non-dialysed group compared with 40.9% for the dialysed group (p <
      0.05). Among 38 variables investigated, only two factors had independent
      prognostic value in multivariate analysis: preoperative serum creatinine > 1.5
      mg/dl (OR = 4.4, p = 0.006) and graft dysfunction grades III-IV (OR = 8.9, p =
      0.001). In conclusion, ARF is a severe complication post-LT; its appearance could
      be predicted in patients with pre-transplant renal dysfunction, severe graft
      dysfunction, or both. However, in many cases renal function may revert to normal
      if treated aggressively with early dialysis support.

PMID- 9575401
TI  - Prognostic value of dipyridamole thallium-201 screening to minimize perioperative
      cardiac complications in diabetics undergoing kidney or kidney-pancreas
      transplantation.
AB  - To minimize perioperative cardiac events, we utilize a screening protocol
      consisting of intravenous dipyridamole thallium-201 myocardial imaging (DPT),
      with the selective use of coronary angiography based on the presence of
      reversible defect(s) on DPT test. A retrospective study was performed to
      determine the prognostic value of this protocol and to identify any clinical
      parameters predictive of an abnormal DPT test. To accomplish this, a detailed
      chart analysis of 176 consecutive kidney (n = 89) and kidney-pancreas (n = 87)
      transplant recipients who had undergone pretransplant DPT testing was performed.
      The results of the DPT test were interpreted as normal in 111, fixed defect in
      15, and reversible defect(s) in 50 patients. Forty-two of the 50 patients with
      reversible defect(s) underwent coronary angiography. Twelve of the 27 patients
      with significant coronary artery disease (CAD, > 50% stenosis in one or more
      coronary arteries) underwent pretransplant revascularization and the remaining 15
      were treated medically. Cardiac events (documented acute myocardial infarction or
      sudden cardiac death) within 6 wk of transplant were stratified by the results of
      this protocol. Also, various clinical parameters were compared between patients
      with normal and abnormal (fixed and reversible defect) DPT tests. Only one of the
      111 (0.9%) transplant recipients with a normal DPT test had a perioperative
      cardiac event. None of the 15 (0%) patients with a fixed defect and none of the
      15 (0%) patients with reversible defect(s), but a nonsignificant (< 50%
      narrowing) coronary angiogram, had a perioperative cardiac event. Three of the 27
      (11.1%) patients with reversible defect(s) and significant disease on coronary
      angiography, who had undergone pre-transplant revascularization or were managed
      medically, had a perioperative coronary event. Of 14 recipients parameters
      analyzed, age > 50 yr was the only variable predictive of an abnormal DPT test.
      We conclude that the incidence of perioperative cardiac events in patients with a
      normal or fixed defect, or reversible defect(s) but a nonsignificant (< 50%
      narrowing) coronary angiogram is very low, indicating the high correlation of
      these findings on DPT and an uneventful (cardiac) post-transplant course. The
      incidence of perioperative cardiac complications amongst the high-risk transplant
      recipients with reversible defect(s) and significant CAD on coronary angiogram
      may be minimized by appropriate preoperative medical management or
      revascularization. None of the clinical variables except age > 50 yr was
      predictive of an abnormal DPT test.

PMID- 9575402
TI  - Lipoprotein abnormalities in long-term stable liver and renal transplanted
      patients. A comparative study.
AB  - Hyperlipidemia is a common feature after organ transplantation. Most studies have
      evaluated the lipid profile in recipients of a particular graft, usually renal.
      In the present work, we studied the lipid profiles of 30 long-term stable liver
      transplant patients (LTP) and compared their pattern with 40 long-term stable
      renal transplant patients (RTP) matched for gender, age, and time from
      transplantation. There were no significant differences between both groups in
      body mass index, serum glucose, serum creatinine, or urinary protein excretion.
      In contrast, RTP had higher pre-transplant total cholesterol and triglycerides,
      received higher doses of steroids (both average and cumulative) and had higher
      cycosplorine blood levels. After a mean time of 60 months after transplantation,
      RTP exhibited higher levels of total serum cholesterol (226 +/- 26 vs. 180 +/- 39
      mg/dl; p = 0.000 002) and low-density lipoprotein (LDL) cholesterol (152 +/- 22
      vs. 112 +/- 37 mg/dl; p = 0.00001). In contrast, there were no differences
      between RTP and LTP in high density lipoprotein (HDL) cholesterol, very low
      density lipoprotein (VLDL) cholesterol, total triglycerides, VLDL triglycerides,
      or lipoprotein (a) [Lp(a)]. By univariate analysis in the whole group, renal
      graft, prednisone daily dose, cyclosporine blood levels, pre-transplant
      cholesterol, and triglycerides were associated with increased post-transplant
      cholesterol levels. By multivariate analysis, prednisone daily dose was the only
      independent variable predicting increased post-transplant serum cholesterol
      levels. The present data show that hypercholesterolemia is more frequent among
      RTP than among LTP. In addition, our data suggest that corticosteroid therapy,
      rather than the transplanted organ, may be the major contributor to this
      difference.

PMID- 9575403
TI  - [The pharmacological correction of factors limiting human work capacity].
AB  - The problem of pharmacological correction of working capacity and rehabilitation
      after exhausting physical exertion is discussed from the standpoint of current
      advances and detection of factors limiting man's working capacity. The removal of
      factors interfering with the development of optimal possibilities of man through
      the effect of medicinal drugs is considered. The article discusses the energy
      sources providing for the performance of physical work differing in power and
      duration in accordance with the specificity of a type of sports as a most
      convenient model for studying adaptation to physical exertion. Factors limiting
      the working capacity of athletes are classified on the basis of current advances
      in biochemistry and physiology. All pharmacological agents influencing human
      working capacity are classified according to the potency zones determining the
      supply of energy. Pharmacological monitoring of man's capacity for work is in
      fact disclosure of factors limiting it and their pharmacological correction. This
      allows planning of the means for excluding the use of dope drugs in sports
      medicine and scientifically substantiated use of drugs in heavy branches of
      industry, for promoting climato-zone adaptation, and in extreme conditions. It is
      shown that the use of strongly active drugs is not necessary because a large
      reserve is available of drugs of plant and animal origin possessing much lesser
      side effects.

PMID- 9575405
TI  - [The delivery of loperamide to the brain by using polybutyl cyanoacrylate
      nanoparticles].
AB  - The possibility of using polysorbate 80-coated nanoparticles for the delivery of
      the water insoluble opioid (lyonist loperamide across the blood-brain barrier was
      investigated. The analgesic effect after i.v. injection of the preparations was
      used as the indication of drug transport through this barrier. Intravenous
      injection of the particulate formulation resulted in a long and significant
      analgesic effect. A polysorbate 80 loperamide solution induced a much less
      pronounced and very short analgesia. Uncoated nanoparticles loaded with
      loperamide were unable to produce analgesia. Polysorbate 80-coated PBCA
      nanoparticles loaded with loperamide led to the transport of loperamide to the
      brain.

PMID- 9575404
TI  - [The seizures induced by N-methyl-D,L-aspartate administration are accompanied by
      an enhancement of nitric oxide generation and of lipid peroxidation processes in
      the rat brain].
AB  - EPR-spectrometry was performed to study the nitrous oxide (NO) content and the
      intensity of lipid peroxidation (LPO) in the brain cortex of rats during
      convulsions induced by intracerebral injection of N-methyl-D,L-aspartate (NMDLA).
      It was shown that the convulsions were attended with a fourfold increase in the
      NO content and activation of LPO in the rat brain cortex. Disocilpin injection
      fully prevented the development of convulsions as well as increase in the NO
      level and LPO activation caused by NMDLA injection. N-nitro-L-arginine had an
      anticonvulsive effect and prevented increase in the NO content but did not cause
      any noticeable effect on LPO intensity in the brain cortex.

PMID- 9575407
TI  - [The mechanism of the action of opiate receptor antagonists in acute shock
      induced blood loss].
AB  - Experiments on 81 rabbits showed that intravenous infusion of naloxone and
      nalorphine in different periods of hemorrhagic shock promoted the death of
      animals. It is concluded that in hypoxia only the antagonistic activity of the
      drugs is manifested as total inactivation of the endogenous opioid system
      depriving it of its protective functions. Nalorphine infused after blood
      reinfusion exhibits agonistic activity and additional activation of the
      endogenous opioid system promotes the use of the biological reserves by the
      organism, which saves some of the animals from death or essentially prolongs the
      survival of the others. Infusion of naloxone after blood transfusion has no
      effect on the outcome.

PMID- 9575406
TI  - [Morphine antibodies in the mechanisms of morphine resistance, morphine tolerance
      and of the action of an antagonist].
AB  - It was found that the absence of the analgesic effect of morphine, as determined
      by the tail-flick test, in morphine-resistant and morphine-tolerant rats, as well
      as in naloxane blockade of morphine analgesia in morphine-sensitive rats was
      attended with a four- to eight-fold increase in morphine antibodies in the
      plasma, as determined by the ELISA method. It is suggested that a pharmacokinetic
      factor mediated through immune reactions of morphine antibodies formation is one
      of the mechanisms of such conditions.

PMID- 9575408
TI  - [The effect of gidazepam on the cardiovascular system function in patients with
      neurotic reactions and in healthy subjects under aggravated conditions].
AB  - Administration of 0.05 g gidazepam once or twice daily for 7 days increased the
      stroke volume (SV) and circulation volume (CV) and reduced total peripheral
      resistance in neurotic patients. In healthy individuals 0.05 g gidazepam
      administered 60 min before an important examination stabilized CV. In subjects
      kept for 60 min in a microclimate with increasing temperature (55 +/- 2 degrees
      C, relative humidity 75-80%, rate of movement 1.5 m/min, rectal temperature at
      the end of exposure 39 degrees C) 0.05 g gidazepam administered 60 min before
      overheating optimally reorganized the reaction of the cardiovascular system,
      stabilized the SV at the initial level, which together with the growing heart
      rate increased the CV and provided sufficient perfusion of the vital organs. In
      healthy subjects working as operators for 4 h under conditions of hypercapnia
      (1.5% CO2), a single administration of 0.05 g gidazepam one hour before the
      beginning of work reduced the pulse pressure and increased the SV. The results
      obtained are evidence of the safety of using gidazepam as a corrector of emotion
      induced disorders in operator performance under extreme conditions.

PMID- 9575409
TI  - [The action of Essentiale and its combination with cordiamine and vitamin E on
      the processes of xenobiotic biotransformation and lipid peroxidation and on liver
      structure in rats with cholestasis].
AB  - Intensive regeneration of cholangia and cholangioles, fibrosis, microglobular
      cirrhosis, vacuolar and granular dystrophy, and necrosis of hepatocytes were
      found in the liver of rats 36 days after ligation of the common bile duct. Lipid
      peroxidation was activated, the activity of the mono-oxidase system was inhibited
      in maintained function of glucuro- and glutathione transferase. Essentiale (per
      os in starch mucilage, 1 ml/kg. for 35 days) increased the activity of cytosol
      glutathione-S-transferase and normalized the decreased blood plasma antioxidant
      activity. Combination of essentiale with cordiamin (nikethamide) and viatmin E
      (50 mg/kg for 35 days) considerably activated the mono-oxigenase, glucoro- and
      glutathione transferase systems of the liver: the free-radical processes became
      less intense. The structure of the liver improves insignificantly in both methods
      of treatment.

PMID- 9575410
TI  - [The modulating effects of preparations of Baikal skullcap (Scutellaria
      baicalensis) on erythron reactions under conditions of neurotic exposures].
AB  - Preparations of Scutellaria baicalensis, namely its dry extract and the
      bioflavonoid baicalin stimulate erythropoiesis depressed in deprivation of the
      paradoxical phase of sleep. After a conflict situation, when hemopoiesis is
      activated, both drugs normalize it. The modulating effect of drugs on hemopoiesis
      in exposure to neurotic factors is a consequence of their influence on the
      functional state of the cell elements of the hemopoiesis-inducing
      microenvironment. The capacity of the Scutellaria baicalensis drugs for reducing
      the effect of psychoemotional stress on the blood system is apparently related to
      their influence on the adrenergic structures.

PMID- 9575411
TI  - [The effect of pyrimidine derivatives on the sulfhydryl status of immunocompetent
      cells in vivo: the interrelationship with Ca2(+)-ATPase and antimutagenic
      activity].
AB  - It was demonstrated in experiments on guinea pigs that a 30 mg/kg dose of ximedon
      changes the content of SH-groups in immunocompetent cells depending on the
      duration of drug administration and the organ to which the cells under test
      belong. Maximum increase of the SH-groups was recorded in the thymocytes. The
      dynamics of changes in Ca(2+)-ATPase activity repeated the fluctuations in the SH
      group content in the splenic and bone marrow cells. In the bone marrow cells of
      CBA x C57B1 mice 3 mg/kg ximedon suppressed the induction of chromosome
      aberrations caused by cyclophosphane. The interrelationship of changes in the
      cell sulfhydryl status with Ca(2+)-ATPase activity and the antimutagenic effect
      of ximedon is discussed.

PMID- 9575412
TI  - [A new property of aspirin and other salicylates. Their capacity for radical
      generation at the expense of chelating-oxidizing action on iron cations].
AB  - It was demonstrated that salicylic acid, by binding ions of ferrous iron, induces
      its oxidation to the oxide form by molecular oxygen with generation of active
      forms of oxygen. Salicylic acid may therefore form stable ferrosalicylic
      complexes only with iron oxide, in which case the affinity of salicylic acid for
      iron oxide is higher than that of o-phenanthroline and lower than that of EDTA.
      In the presence of ascorbate in the system with salicylic acid and iron ions
      continuous radical formation may take place due to alternating cycles of
      oxidation-reduction iron ions through the combined effect of salicylic acid and
      ascorbate on them. The initial salicylic acid content in commercial aspirin
      preparations and its intensive formation at pH values close to the physiological
      parameters were determined by colorimetry and the inner standard method. After
      incubation of aspirin preparations at pH close to the physiological values,
      accelerated oxidation of ferrous iron with formation of active oxygen forms was
      recorded, which was evidently due to salicylic acid produced as the result of
      aspirin breakdown under such conditions.

PMID- 9575413
TI  - [Iodoantipyrine--an agent for treating and preventing tick-borne encephalitis].
AB  - The antiviral activity of iodantipyrine was studied in outbred [correction of
      inbred] albino mice (weight 10-12 g) infected with the Absettarov strain of the
      tick-borne encephalitis virus. Iodantipyrine was administered per os or
      parenterally and the animals were observed for 21 days. A reliable therapeutic
      effect was produced in 60% of mice infected with 10 DL50 of tick-borne
      encephalitis virus which were given the drug per os in a dose of 50 mg/kg.
      Preventive administration of the drug was effective in 47% of the animals.

PMID- 9575414
TI  - [The mechanisms of the hepatotoxic action of the antitumor preparation vepesid].
AB  - It was shown in experiments on rats that intravenous infusion of the antitumor
      drug vepesid in a maximum tolerated dose causes stimulation of free-radical
      oxidation and changes in the fractional composition of lipids and phospholipids
      in the hepatic tissue. Changes in the activity of aminotransferases and alkaline
      phosphatase in the blood were recorded.

PMID- 9575415
TI  - [The mechanism of the effect of the cholinesterase reactivator diethyxime on
      different models of the development of delayed hypersensitivity in acute
      dichloroethane poisoning].
AB  - Formation of DTH to sheep red blood cells was studied in CBA mice on different
      models in acute DCE poisoning (0.75 LD50). The effect of the reactivator
      cholinesterase diethyxime on this reaction in acute poisoning, and the relation
      of the reactions under study in various experimental series with the activity of
      alpha-naphthyl-AS-acetatesterase in the spleen cells and popliteal lymph nodes
      were also studied. Acute DCE poisoning (0.75 LD50) lowered cellular immunity
      which was assessed according to DTH formation in various models due to decrease
      of alpha-naphthyl-AS-acetatesterase activity in the splenocytes and cells of the
      of the suppressor cells in the DTH reaction. The reaction was attended with
      decrease of alpha-naphthyl-AS-acetatesterase in the splenocytes of the donors and
      the popliteal lymph nodes of the recipients apparently due to relative prevalence
      in the spleen cells of T-suppressors which are distinguished by poor esterase
      activity. Diethyxime restored completely the formation of DTH studied in
      different models (with the exception of the reaction in which the effect of
      transfer of the suppressor cells was assessed) due to restoration of alpha
      naphthyl-AS-acetatesterase activity in the cells of the lymphoid organs.

PMID- 9575416
TI  - [The effect of the antioxidants elton and leveton on the physical work capacity
      of athletes].
AB  - Study of 44 athletes of various sport skill undergoing training for endurance
      showed the chemiluminescence method to be an important parameter indicating that
      a person is trained for physical exertion. The broad-spectrum adaptogenic agents
      elton and leveton reduced in in-vitro experiments the superweak luminescence of
      urine, which is evidence of their direct antioxidant effect. Twenty-day
      administration of elton and leveton reduced chemiluminescence and the level of
      malonic dialdehyde in the urine of highly skilled athletes and increased their
      physical working capacity tested by bicycle ergometry with gradually increasing
      physical loads.

PMID- 9575417
TI  - [Dopamine receptors. Their role in regulating the activities of the heart and
      vessels].

PMID- 9575418
TI  - [The current possibilities for the pharmacological regulation of myocardial
      metabolism in experimental catecholamine-induced necroses].
AB  - Catecholamine-induced myocardial necroses have their own peculiarities but the
      disorders in myocardial metabolism occurring in them do not differ in quality
      from those encountered in necroses caused by occlusion of the coronaries.
      Pharmacological regulation of the metabolism of a myocardium damaged by
      catecholamines may be accomplished by the same drugs which are used in necroses
      caused by coronary occlusion, but agents with antihypoxic and antioxidant
      activity are preferable.

PMID- 9575419
TI  - [Antioxidants in the combined therapy of diabetic angiopathies].
AB  - The participation of free-radical oxidation of lipids and polymers in the
      pathogenesis of diabetic angiopathies is analysed. The structure of the system of
      antioxidant protection and the mechanisms of damage to the vascular wall
      macromolecules in diabetic angiopathies is suggested. The protective effects of
      antioxidants in experimental studies and clinical practice are discussed. The
      conditions for and the principles of applying antioxidants in complex therapy of
      diabetic angiopathies are suggested.

PMID- 9575420
TI  - Anti-neoplastic properties of human corticotropin releasing factor: involvement
      of the nitric oxide pathway.
AB  - We report a series of the in vivo and in vitro studies that evaluate the anti
      neoplastic potential of hCRF in W256 rat mammary carcinoma. Using magnetic
      resonance imaging (MRI) and direct measurements of tumor and peritumoral brain
      water content we found that hCRF treatment (100 micrograms/kg subcutaneously
      twice a day for 3 days) caused significant inhibition of growth and vascular
      permeability of the i.c. W256 tumors. hCRF also exhibited antiproliferative and
      differentiation-inducing effects in W256 cells in vitro. The calculated IC50
      values were 70 nM and 100 nM of hCRF, as measured by digital videomicroscopic
      quantitation of tumor cell population growth rate and by [3H]-thymidine
      incorporation assay, respectively. The observed effects in W256 cells were CRF
      receptor mediated. This was shown in two ways: by the presence of relatively high
      levels of CRF1 receptor mRNA in W256 cells, and by the fact that the tumor growth
      inhibitory and differentiation inducing effects of hCRF in vitro were abolished
      by the CRF receptor antagonist a-helical CRF (9-41). Antiproliferative and
      differentiation inducing effects of hCRF in W256 cells involve activation of
      nitric oxide synthase (NOS) and L-arginine-NO pathway. This was shown by using
      the inhibitor of NOS, the L-nitro-arginine methyl esther (L-NAME), which
      prevented the antiproliferative and differentiation inducing effects of hCRF in
      vitro. The cytotoxicity of NO in W256 cells was assessed by the addition of
      sodium nitroprusside (SNP) to the media. SPN exhibited dose-dependent
      cytotoxicity in W256 cells with IC50 of 100 muM SNP as measured by [3H]-thymidine
      incorporation assay. We conclude, that hCRF has substantial anti-neoplastic
      effects which include inhibition of proliferation and induction of
      differentiation of the tumor cells in vitro, and a decrease in tumor vascular
      permeability (and possibly neo-angiogenesis) in vivo.

PMID- 9575421
TI  - Improving the tumor specificity and retention of antibody-based molecules.
AB  - A number of novel strategies have been employed to enhance the degree and
      specificity of tumor-targeting by antibody-based molecules. These fall into three
      overlapping categories. The augmentation of the interaction between the antibody
      and target antigen (e.g., through increased affinity or valence), the enhancement
      of targeting specificity (e.g., by altering the clearance of unbound antibody or
      radiolabel), and the selection of radioisotopes and labeling methods which are
      more stable in vivo or better suited to the target application.

PMID- 9575423
TI  - Angiogenic molecules and cancer metastasis.
AB  - The progressive growth of primary neoplasms and metastases depends on the
      development of adequate vasculature, i.e., angiogenesis. The extent of
      vascularization in different malignancies correlates directly with their
      metastatic potential and, hence, inversely with the survival of the patient. The
      induction of neovascularization is mediated by both tumor cells and host cells
      and the interaction of the two. The balance of positive and negative regulatory
      molecules released by tumor cells and host cells determines the biological
      outcome which, in the case of tumor growth, favors angiogenesis.

PMID- 9575422
TI  - Individuals at high risk for lung cancer have airway epithelial cells with
      chromosome aberrations frequently found in lung tumor cells.
AB  - Identification of individuals at greatest risk of developing lung cancer could
      enhance the efficacy of intervention modalities, thereby greatly reducing
      mortality from this disease. One strategy for identifying these people is to
      establish molecular markers which reflect the severity of their cancerization
      field. Thus, investigations were initiated to determine of cells with chromosome
      aberrations frequently exhibited by lung tumor cells, i.e., trisomy 7, trisomy
      20, and deletion of 9p23, are prevalent within the uninvolved airways of cancer
      patients. As a result, cells containing these aberrations were consistently found
      at significantly elevated levels by using fluorescence in situ hybridization
      (FISH). In contrast, cells collected from non-smokers who had never smoked were
      normal by this assay. The next objective was to determine of cells exhibiting
      these alterations are also present in upper airways of exposed, but cancer-free
      smokers and ex-uranium miners. The results showed that, although only a subset of
      these people will develop lung cancer in their lifetimes, they universally harbor
      increased numbers of abnormal cells within their airway epithelium. However, the
      number of sites with multiple verities of abnormal cells tended to be fewer
      compared with the cancer patients. Thus, quantifying cells with molecular
      alterations within the cancerization field of a smoker may delineate those with a
      lesser grade of damage, and these individuals may be at a lesser risk of
      developing disease. However, differences in the extent of genetic damage afforded
      by these assays may not clearly define individuals with pending disease, and
      additional molecular assays must be devised.

PMID- 9575424
TI  - Novel molecular and cellular strategies in cancer therapy.
AB  - Tumor initiation and progression results from several subsequent mutations in
      genes that control cellular proliferation and differentiation. Neoplasia may lead
      to the expression of antigens that may be derived from such oncogenes or the
      activation of other cellular or viral genes that may represent tumor associated
      antigens. This review summarizes the present understanding of these mechanisms in
      an effort to design new therapeutic strategies.

PMID- 9575425
TI  - Molecular epidemiology of breast cancer.
AB  - Molecular epidemiology evaluates cancer risk based upon environmental exposures
      and genetically determined susceptibilities. Biomarkers, molecular indicators of
      exposure or disease state, are used to stake out the progression of a disease
      along plausible mechanistic pathways. Connecting biomarkers of exposure, (e.g.,
      carcinogen DNA adducts), effect (e.g., mutations in tumor suppressor genes), or
      disease (e.g., histological abnormalities) can clarify the etiology of cancer,
      improve risk estimates, and lead to better preventive strategies. In this review,
      the following evidence is used to evaluate the possible contribution of
      environmental carcinogens to breast cancer: a) genetic predispositions in
      familial breast cancer, b) mutational spectra of the p53 tumor suppressor gene,
      c) chemical carcinogenesis in breast cancer models, and d) genetic polymorphisms
      in sporadic breast cancer.

PMID- 9575426
TI  - Prostate cancer metastasis-suppressor genes: a current perspective.
AB  - Prostate cancers account for 43% of all cancers diagnosed in American men. It is
      estimated that in 1996, 317,000 new cases of prostate cancer were diagnosed and
      41,000 men died of the disease. The challenge of treating prostate cancer lies in
      accurately distinguishing those histologically-localized cancers which will
      complete metastatic progression from those that will remain indolent. At this
      time, we lack appropriate histological markers to make such distinctions,
      therefore, it is often difficult to accurately predict the clinical course of an
      individual patient's disease. There is growing evidence that a critical event in
      the progression of a tumor cell from a non-metastatic to metastatic phenotype is
      the loss of function of metastasis-suppressor genes. These genes specifically
      suppress the ability of a cell to metastasize. Work from several groups has
      demonstrated that human chromosomes 8, 10, 11 and 17 encode prostate cancer
      metastasis suppressor activities. As a result of these efforts the first prostate
      cancer metastasis-suppressor gene, KAI1, was identified and mapped to the p11-2
      region of chromosome 11. In subsequent studies, an additional gene encoded by the
      same region, CD44 was also determined to have metastasis-suppressor activity.
      Recent studies have shown a correlation between decreased expression of KAI1 and
      CD44 and an increased malignant potential of prostate cancers. It is anticipated
      that the identification of other metastasis suppressor genes may allow for the
      development of diagnostic markers useful in the clinical substaging of individual
      tumors. This manuscript is intended to present our perspective on the importance
      of these genes in the understanding of prostate cancer progression. More
      importantly, we present new findings from our laboratory's effort to identify the
      metastasis-suppressor genes encoded by human chromosome 17. Specifically we
      report the strategy currently being used to evaluate a series of candidate genes
      and the approach being utilized to pinpoint the metastasis-suppressor region on
      human chromosome 17.

PMID- 9575427
TI  - Recent advances, prospects and problems in designing new strategies for
      oligonucleotide and gene delivery in therapy.
AB  - The field of gene therapy has been in rapid expansion since the first submissions
      of gene therapy trials in the early 1990s which provided encouraging results.
      Since then, many gene therapy protocols have been approved for phase I clinical
      trials for the treatment of inherited genetic diseases and cancer. The
      possibility of employing gene transfer technology to treat AIDS and neurologic
      diseases is currently under evaluation. Many gene delivery systems have been
      developed for in vivo studies and therapy. The efficiency of in vivo gene
      transfer, however, still needs to be optimized, even though significant advances
      have recently been achieved in improving gene delivery, gene regulation and
      avoidance of immune responses. This review provides a general outline focusing on
      the description of the most common gene delivery systems and on their current
      applications in therapeutics.

PMID- 9575428
TI  - Studies on circadian periodicity of urinary corticoids in carcinoma of the
      breast.
AB  - The circadian periodicity of urinary 17-ketogenic steroids (17-KGS), 17
      ketosteroids (17-KS) and creatinine (Cr) was studied preoperatively and on the
      9th postoperative day in 25 histopathologically proved breast cancer patients and
      in 15 healthy Indian women under tropical conditions. A statistically significant
      rhythm was observed in healthy participants for all three variables. Urinary
      corticoids were markedly elevated in breast cancer patients irrespective of the
      stage of the disease in comparison with healthy controls. The degree of elevation
      was more pronounced preoperatively in advanced stage breast cancer in comparison
      with other groups. After mastectomy, the values of all three variables declined
      markedly, approaching usual values with a circadian rhythm resembling the pattern
      found in clinical health.

PMID- 9575429
TI  - Inhibition of glioma invasion of fetal brain aggregates.
AB  - Glioblastoma multiforme is a malignant primary brain tumor associated with short
      patient survival in part because of the ability of individual cells to migrate
      significant distances into brain tissue. Invasion is a difficult process to
      model, because many such human tumors do not invade immunologically competent
      animal tissue, tumors grown in animals do not invade human tissue, and relevant
      human tissue substrates are not easily reproduced. We discuss models for
      examining invasion in vitro, and in particular review work using the tumor
      spheroid--fetal rat brain aggregate co-culture model, assessed with confocal
      microscopy and four-dimensional imaging. Quantitation of invasion in this model
      is discussed, as well as the invasion-inhibitory properties of tyrosine kinase
      (TK) inhibitors. The effects of receptor-specific tyrphostins strongly support a
      dominant role for Epidermal Growth Factor Receptor activation in this process and
      show that invasion can be effectively inhibited at much lower concentrations of
      TK inhibitors than is necessary for growth suppression. Inhibition of activation
      of the purported growth factor receptor second messenger phospholipase C- gamma
      1, by pharmacological means and gene transfection, also profoundly inhibits the
      invasive properties of human glioblastoma and rat C6 glioma cells. We have
      assessed invasiveness in several human tumor specimens, which may provide
      information relative to prognosis and recurrence risk. Our data supports the
      concept of differential control of invasion and proliferation, and points to
      possible strategies for anti-invasive therapy for glioblastoma multiforme.

PMID- 9575430
TI  - Prognostic role of proliferating cell nuclear antigen in lung cancer: an
      immunohistochemical analysis.
AB  - Proliferating cell nuclear antigen (PCNA) is a 36 kDa protein acting as a subunit
      of DNA polymerase delta, and is therefore associated with DNA replication. Its
      involvement in DNA excision repair after DNA sub-lethal damage has been reported.
      We assessed the immunohistochemical expression of PCNA in 94 lung cancer
      specimens in order to evaluate its potential relationship with clinical history
      and the outcome of the evaluated patients. We found PCNA protein expressed in all
      the evaluated neoplastic specimens, but with different expression levels. In
      addition, our results showed a subgroup of patients (high expressors) having a
      statistically significant worse outcome compared to the other two groups of
      patients, independently of' any other clinico-pathological feature. In
      conclusion, our data highlight the central role of PCNA and estimation of the
      proliferation rate in the prediction of the prognosis of lung cancer patients.

PMID- 9575431
TI  - The etiology of second primary neoplasms.
AB  - Neoplasms are derived from normal tissues of the body by cellular transformation.
      Tumors often represent a less differentiated or an undifferentiated version of
      the histology of the neoplasms original tissue. Primary tumor(s) may spread by
      direct extension or by metastasis. For the purpose of this review, second primary
      tumors will be defined to exclude metastatic lesions or recurrences from an
      original primary tumor. Second primary tumors arise in several different clinical
      situations that basically are the result of either inherited or acquired genetic
      mutations. Second primary tumors may develop soon or very late after treatment of
      the first primary tumor and may reflect an underlying genetic or immunologic
      defect in the patient, treatment related genetic damage, or environmental
      exposure to carcinogens. With the greater success of modern chemotherapy and
      radiotherapy in achieving long-term remissions in many patients, second primary
      tumors are a rapidly developing disease-category. This paper will review the
      clinical circumstances associated with a significantly higher incidence of second
      primary tumors in patients with an initial primary tumor.

PMID- 9575432
TI  - Mechanisms of hormone independence in human breast cancer.
AB  - The progression of human breast cancer from a hormone dependent to a hormone
      independent phenotype is a clinical problem which limits the long term usefulness
      of the relatively nontoxic endocrine therapies. It is also associated with a more
      aggressive form of the disease. Since expression of estrogen receptor-alpha
      appears to be relatively stable phenotype during breast cancer progression, the
      majority of breast tumors that develop hormone independence and resistance to
      endocrine therapies do so despite the continued expression of estrogen receptor
      alpha. Several possible mechanisms that may contribute to the progression of
      breast cancer from hormone dependence to independence, either alone or in
      combination with other mechanisms, are reviewed. These include variant or mutated
      estrogen receptor-alpha, ligant independent activation of estrogen receptor
      alpha, altered expression of down-stream estrogen target genes, post receptor and
      pharmacological alterations.

PMID- 9575433
TI  - The spontaneous regression of neoplasms in mammals: possible mechanisms and their
      application in immunotherapy.
AB  - In mammalian cells, neoplastic transformation is directly associated with the
      expression of oncogenes, with the mutation, loss or simple inactivation of the
      function of tumor suppressor genes, and the production of certain growth factors.
      Genes for suppression of the development of the malignant immunophenotype, as
      well as inhibitory growth factors have regulatory functions within the normal
      processes of cell division and differentiation. Telomerase (a ribonucleoprotein
      polymerase) activation is frequently observed in various cancers. Telomerase
      activation is regarded as essential for cell immortalization and its inhibition
      may result in the spontaneous regression (SR) of neoplasms. SR of neoplasms
      occurs when the malignant tumor mass partially or completely disappears without
      any treatment or as a result of a therapy considered inadequate to influence
      systemic neoplastic disease. This definition makes it clear that the term SR
      applies to neoplasms in which the malignant disease is not necessarily cured, and
      to cases where the regression may be neither complete nor permanent. A number of
      possible mechanisms of SR are reviewed, with the understanding that no single
      mechanism can completely account for this phenomenon. The application of the
      newest immunological, molecular biological and genetic insights for more
      individualized anticancer immunotherapy (biotherapy) is also discussed.

PMID- 9575434
TI  - Apoptosis in the mammalian thymus during normal histogenesis and under various in
      vitro and in vivo experimental conditions.
AB  - Programmed cell death (PCD), also known as apoptosis, is a genetically controlled
      cellular response, manifested in morphologically distinct non-necrotic cellular
      destruction: cell shrinkage, cytoplasmic "boiling", condensation of chromatin,
      loss of nuclear membrane followed by DNA fragmentation and cell membrane
      blebbing, all of which initiate the formation of apoptotic bodies. During the
      early stages of PCD, cell membrane phospholipid asymmetry is altered, resulting
      in the dislocation of phosphatidylserine (PS) to the cell surface. During
      apoptosis, DNA is cut by endonucleases at DNA-linked sites between nucleosomes,
      producing a number of multimers of nucleosomal DNA units in the cell nuclei. The
      mechanism of apoptosis and the cellular signals involved in its induction have
      been studied during thymic prenatal ontogenesis and postnatal development, mainly
      in immature thymocytes and in the cells of the reticulo-epithelial (RE) network.
      In thymocytes or resting T lymphocytes, p53 tumor suppressor protein was
      identified to be a critical mediator of apoptosis in response to DNA damage. The
      cellular interaction of immature, cortical thymocytes (characterized by a double
      positive CD4+CD8+TCRlow immunophenotype) with thymic RE cells induces positive
      selection of T lymphocytes that recognize, but are not activated by self-MHC
      molecules (tolerance induction). Double positive CD4+CD8+CD3- thymocytes undergo
      Fas-mediated apoptosis, while CD4+CD8+CD3+ cells use the CD3 mediated pathway of
      PCD. Two step, apoptotic cell death is mainly restricted to the CD4+CD8+TCRdull
      thymocyte subpopulation. T-lymphocytes which do not undergo positive selection
      are killed by apoptosis in response to a number of intrinsic and extrinsic
      factors, such as chemical toxins, viral infections, X- and UV irradiation, mild
      hyperthermia, the actions of various hormones, extracellular survival factors,
      calcium ionophores (such as A23187), various chemotherapeutic drugs (adriamycin,
      actinomycin D, etc) and antibodies directed to the CD3-TCR (T cell receptor)
      complex. Immature thymocytes also undergo a second selective process, so-called
      negative selection, when thymic stromal cells eliminate autoreactive T
      lymphocytes. This process has been termed clonal deletion and also involves
      apoptosis. In addition to the two intrathymic T lymphocyte selection mechanisms,
      Immunocompetent, but autoreactive T lymphocytes which have already reached the
      periphery are also eliminated by apoptosis. All the divers stimuli of PCD are
      associated with an increase in the concentration of cytosolic calcium ions
      (Ca+2), which activate an endogenous endonuclease. This trigger for PCD results
      in rapid cleavage of DNA, a hallmark of apoptosis. Despite the diversity of the
      signals that can trigger apoptosis, the changes in cellular morphology
      characteristic of PCD are very similar. The uniformity of the morphological
      changes suggests the existence of a predetermined, final and common cell suicide
      pathway. Apoptosis requires energy in the form of ATP, indicating that PCD, as
      opposed to necrosis, is an energy dependent, active physiological and
      pathophysiological phenomenon.

PMID- 9575435
TI  - Metalloproteases and urokinase in angiogenesis and tumor progression.
AB  - Following malignant transformation, tumor cells and their surrounding stroma
      produce a variety of growth factors and proteolytic enzymes to induce new
      capillary formation (angiogenesis) and matrix degradation to promote tumor
      development. Two key families of proteases, matrix metalloproteases (MMPs) and
      urokinase (uPA) are now strongly implicated in this process of angiogenesis and
      matrix degradation. Both MMPs and uPA are abundantly produced by various tumors
      where their level of expression can serve as prognostic markers. Using gene
      transfer techniques, overexpression of these proteases and their receptors
      enhances the invasive and metastatic potential of tumor cells. Furthermore,
      blockage of actions of MMPs and uPA by molecular and chemical approaches results
      in a marked decrease in tumor growth to further validate the significance of
      these enzymes as targets for anti-cancer therapy.

PMID- 9575436
TI  - [Survey of the sensitivities of clinical isolates to antibacterial agents (annual
      report)].
AB  - Research groups were formed in 21 institutions nationwide to investigate
      carbapenem resistance. The activities of various antibacterial agents,
      principally carbapenems were tested against clinical isolates collected from
      these institutions. The broth microdilution method was used to determine the
      minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,282
      strains of 11 bacterial species isolated at all institutions between October and
      December 1995. The results were as follows: 1. Carbapenems exhibited strong
      antibacterial activities against MSSA and Streptococcus pneumoniae. Their
      activities against Enterococcus faecalis were comparable to that of ABPC.
      Carbapenems showed low activities against MRSA. 2. OFLX exhibited the greatest
      antibacterial activity against Haemophilus influenzae, followed by MEPM. The
      antibacterial activities of the other carbapenems were comparable to those of
      FMOX and CTM. 3. The carbapenems showed high activities against Escherichia coli,
      Klebsiella pneumoniae, Enterobacter cloacae, and Bacteroides fragilis group.
      Their activities were greater than that exhibited by other beta-lactam
      antibacterial agents. The carbapenems also exhibited greater antibacterial
      activities against Serratia marcescens than the other beta-lactam antibacterial
      agents, but some resistant strains were detected. 4. The antibacterial activities
      of carbapenems against Pseudomonas aeruginosa were comparable to those of CAZ,
      AZT, AMK.

PMID- 9575437
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1996). I.
      Susceptibility distribution].
AB  - The frequencies of isolation and susceptibilities to antimicrobial agents were
      investigated on 680 bacterial strains isolated from patients with urinary tract
      infections (UTIs) in 10 hospitals during the period of June 1996 to May 1997. Of
      the above bacterial isolates, Gram-positive bacteria accounted for 30.4% and a
      majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for
      69.6% and most of them were Escherichia coli. Susceptabilities of several
      isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus
      faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis
      isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM)
      and vancomycin (VCM) were also active with the MIC90S of 2 micrograms/ml. The
      others had low activities with the MIC90S of 16 micrograms/ml or above. 2.
      Staphylococcus aureus including MRSA Arbekacin (ABK) and VCM showed the highest
      activities against both S. aureus and MRSA isolated from patients with UTIs. The
      MIC90S of them were 1 or 2 micrograms/ml. The others except minocycline (MINO)
      had low activities with the MIC90S of 32 micrograms/ml or above. 3.
      Staphylococcus epidermidis ABK and VCM showed the strongest activities against S.
      epidermis isolated from patients with UTIs. The MICs for all strains were equal
      to or lower than 2 micrograms/ml. Cefazolin (CEZ), cefotiam (CTM) and cefozopran
      (CZOP) were also active with the MIC90S of 4 micrograms/ml. Compared with
      antimicrobial activities of cephems is 1995, the MIC90S of them had changed into
      a better state. They ranged from 4 micrograms/ml 16 micrograms/ml in 1996. 4.
      Streptococcus agalactiae All drugs except MINO were active against S. agalactiae.
      ABPC, CZOP, IPM, and clarithromycin (CAM) showed the highest activities. The MICs
      for all strains were equal to or lower than 0.125 micromilligrams. Tosufloxacin
      (TFLX) and VCM were also active with the MIC90S of 0.5 micromilligrams. 5.
      Citrobacter freundii Gentamicin (GM) showed the highest activity against C.
      freundii isolated from patients with UTIs. Its MIC90 was 0.5 micrograms/ml. IPM
      and amikacin (AMK) were also active with the MIC90S of 1 microgram/ml and 2
      micrograms/ml, respectively. Cefpirome (CPR) and CZOP were also active with the
      MIC90S of 8 micrograms/ml. The MIC90S of the others were 16 micrograms/ml or
      above. 6. Enterobacter cloacae IPM showed the highest activity against E.
      cloacae. The MICs for all strains were equal to or lower than 0.5 microgram/ml.
      The MIC90S of ciprofloxacin (CPFX) and TFLX were 1 microgram/ml, the MIC90 of AMK
      was 2 micrograms/ml, the MIC90S of CZOP, GM and ofloxacin (OFLX) were 4
      micrograms/ml. The MIC50S of cephems except CEZ, cefmetazole (CMZ) and cefaclor
      (CCL) had changed into a better state in 1996, compared with those in 1995. 7.
      Escherichia coli All drugs except penicillins and MINO were active against E.
      coli. Particularly CPR, CZOP and IPM showed the highest activities against E.
      coli. The MIC90S of them were 0.125 microgram/ml or below. Among E. coli strains,
      those with low susceptibilities to cephems except CEZ, cefoperazone (CPZ),
      latamoxef (LMOX) and CCL have increased in 1996, compared with those in 1995. 8.
      Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except
      penicillins, with the MIC90S of 2 micrograms/ml or below. CPR had the strongest
      activity, the MICs for all strains were equal to or lower than 0.25 microgram/ml.
      Flomoxef (FMOX), cefixime (CFIX), CZOP and carumonam (CRMN) were also active with
      the MIC90S of 0.125 microgram/ml or below. 9. Pseudomonas aeruginosa All drugs
      except quinolones were not so active against P. aeruginosa with the MIC90S were
      32 micrograms/ml or above. Quinolones were more active in 1996 than 1995. The
      MIC90S of them were between 4 micrograms/ml and 8 micrograms/ml, and the MIC50S
      of them were between 1 microgram/ml and 2 micrograms/ml. 10. Serratia marcescens
      GM showed the highest activity against S. marcescens. Its MIC90 was 1 micro

PMID- 9575438
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1996). II.
      Background of patients].
AB  - Clinical background was investigated on patients with urinary tract infections
      (UTIs) from whom 752 bacterial strains were isolated in 10 hospitals during the
      period from June, 1996 through May, 1997. 1. Distribution of age and sex of
      patients and type of infections. Among males, those with ages 40 years or older
      were more frequent, the higher the ages of them. Among females, those with ages
      in the 60's were the most frequent (24.6%), and those with ages in the 20's, 40's
      and 50's were about 13%. With regard to type of infections, more than a half of
      infections among males with ages 30 years or older were of complicated types, but
      most of infections among females were of uncomplicated types, especially among
      females of ages less than 60 years. 2. Ages of patients and types of pathogens.
      The higher the ages of patients, the lesser became the isolation frequencies of
      Escherichia coli, but the higher were those of Pseudomonas aeruginosa and
      Klebsiella spp. 3. Effect of antibiotic use on isolation frequencies of
      pathogens. Use of antibiotics decreased pathogens isolated from patients with
      uncomplicated UTIs drastically (231 isolates before antibiotics compared to 60
      after). Even isolated pathogens from patients with complicated UTIs decreased
      drastically with the use of antibiotics when indwelling catheters were not in use
      (193 isolates before antibiotics compared to 75 after), but when indwelling
      catheters were in use, antibiotics apparently failed to decrease the isolation
      frequency. 4. Surgical procedures and types of causative organisms for UTIs. From
      cases of uncomplicated UTIs, E. coli was the most frequently isolated, followed
      by Enterococcus Faecalis and Klebsiella spp. E. coli was the most frequently
      isolated organism from complicated UTIs without indwelling catheters. When a
      surgical procedures were not done, E. coli was isolated most frequently. From
      cases of complicated UTIs with indwelling catheters, P. aeruginosa, E. coli and
      E. faecalis were the organisms that were mainly isolated, with isolation
      frequencies of 23.2%, 15.2, 12.2, respectively. When no surgical procedures were
      used, isolation frequencies of P. aeruginosa, E. faecalis and Enterobacter spp.
      were 17.2%, 13.8%, 13.8%, respectively.

PMID- 9575440
TI  - [JFR '97 book of abstracts].

PMID- 9575439
TI  - [Fundamental studies on antibacterial activity of clindamycin against
      Propionibacterium acnes].
AB  - Antibacterial activity of clindamycin against Propionibacterium acnes (P. acnes)
      was evaluated in comparison with nadifloxacin in vitro. Using a burned-infected
      mouse model, topical application of 1% gel form of clindamycin phosphate on P.
      acnes was also evaluated in in vivo. (1) The MIC of clindamycin measured by agar
      dilution method was 0.02 microgram/ml, and this value was smaller than that of
      nadifloxacin (0.3 microgram/ml). (2) At concentrations on 1-, 2- and 4- times the
      MIC clindamycin demonstrated bacteriostatic activity on P. acnes and showed
      bactericidal activity at 5-times the MIC. Nadifloxacin showed bacteriostatic
      activity at one half the MIC and bactericidal activity at the MIC. (3) Against
      acquired resistant strains of P. acnes, the highest concentrations of clindamycin
      and nadifloxacin that did not inhibit growth of the organism increased 5-fold
      higher than those against sensitive strain during 25 successive cultures in
      vitro. Therefore, the resistance of P. acnes was found to be emerged at almost
      the same ratio against both agents. (4) The chemotherapeutic effects of 1% gel
      form of clindamycin phosphate and 1% cream of nadifloxacin were evaluated for
      given subcutaneously to infected P. acnes at the burned site in mice. The topical
      application of either agents showed a significant reduction of number of bacteria
      and this result predicted clinical efficacy of topical application of
      clindamycin.

PMID- 9575441
TI  - The immunological system in hemochromatosis.

PMID- 9575442
TI  - Iron, oxidative stress and liver fibrogenesis.

PMID- 9575443
TI  - Hemochromatosis after the gene discovery: revisiting the diagnostic strategy.

PMID- 9575444
TI  - Iron overload in viral and alcoholic liver disease.

PMID- 9575445
TI  - Iron and neoplasia.

PMID- 9575446
TI  - Revisiting various iron overload syndromes after the haemochromatosis gene
      discovery.
AB  - The discovery of the gene responsible for most cases of genetic haemochromatosis
      has made it possible to re-evaluate the role of haemochromatosis in causing iron
      accumulation in porphyria cutanea tarda and various inherited anaemias. Recent
      studies of these associations are reviewed.

PMID- 9575447
TI  - Wilson disease in 1998: genetic, diagnostic and therapeutic aspects.

PMID- 9575448
TI  - Should we screen for factor V Leiden?

PMID- 9575450
TI  - Voluntary registration of unreported randomised trials: an initiative from
      medical editors.

PMID- 9575449
TI  - Down's syndrome screening in twins.

PMID- 9575451
TI  - A comparative study of routine versus selective fetal anomaly ultrasound
      scanning.
AB  - OBJECTIVES: To evaluate the cost-benefit of changing from selective (high risk)
      to routine ultrasound screening for fetal anomaly. SETTING: Women booked by
      general practitioners for primary antenatal care at their local hospital.
      METHODS: Prospective study of the 12 months before and after introduction of
      routine second trimester ultrasound for fetal anomaly at our institution. All
      congenital abnormalities, mode of detection, and outcome were recorded and a cost
      analysis of the programme attempted. RESULTS: In the 12 months of selective (high
      risk) ultrasound policy, detailed second trimester scans were performed in 1007
      (26%) pregnancies. In the 12 months of routine ultrasound anomaly screening,
      scans were performed in 3529 (93%) pregnancies. Routine ultrasound was the sole
      method of detection for 11 major and 18 less severe congenital abnormalities
      found in low risk pregnancies which would not previously have qualified for high
      risk ultrasound. In seven of these cases the parents opted for termination of
      pregnancy, with estimated savings on treatment and long term care of 1,015,546
      pounds. The financial cost of providing the ultrasound screening service at our
      hospital for 12 months was calculated at 57,573 pounds and the resulting
      financial benefit for the year was estimated at 957,973 pounds. CONCLUSION:
      Although it is recognised that many of the emotional and psychological costs and
      benefits of the service are difficult to evaluate, routine fetal anomaly
      ultrasound would seem to be economically justifiable. The financial savings
      achieved at our hospital would translate into a potential annual saving for the
      National Health Service of nearly 170 million pounds if screening were offered in
      all hospitals in England and Wales.

PMID- 9575452
TI  - Attitudes of general practitioners to screening for cystic fibrosis.
AB  - OBJECTIVE: To ascertain the views of general practitioners (GPs) about screening
      for cystic fibrosis. To find out whether and under what conditions they might
      play a part in the delivery of such programmes. SETTING: All GP practices within
      the Lothian Health Board area. METHODS: A self administered questionnaire was
      sent to each of the 532 GPs in the area. RESULTS: 334 (63%) GPs participated in
      the study. Only 23% of these claimed to have no professional or personal
      experience of the disorder. 77% of GPs were aware of the existence of a programme
      of antenatal screening for cystic fibrosis (CF), which had been running in
      Edinburgh for the past six years, with only 2% unfavourably disposed to it.
      However, when asked to rank CF screening against antenatal screening for spina
      bifida and Down's syndrome, or cervical and breast screening, 55% gave it the
      lowest priority. There was fairly equal support for the screening site being an
      antenatal clinic, a genetic centre, a family planning clinic, or a GP surgery,
      but little enthusiasm for programmes in schools or the workplace. Surprisingly,
      only 13% of GPs thought that screening should be offered to those with a negative
      family history of the disorder. Although the idea of involvement in screening was
      favoured, GPs claimed that any aspect of delivery that they undertook would need
      to be supported. There were no significant differences between the responses of
      fundholding GPs and non-fundholders. CONCLUSIONS: The low ranking by GPs of CF
      screening against other programmes, together with the need for support if they
      were to be involved, suggests that it is currently impractical to move the
      programme from its existing site in antenatal clinics.

PMID- 9575453
TI  - Neonatal screening for the cystic fibrosis main mutation delta F508 in Estonia.
AB  - In this pilot study the frequency of delta F508 mutation carriers, their
      geographic distribution, and the prevalence of cystic fibrosis (CF) in Estonia
      were investigated. During the screening programme 7396 newborns were tested for
      delta F508 mutation and 88 were found to carry this deletion. The mean frequency
      of delta F508 mutation carriers in Estonia was thus estimated as 1 out of 84 live
      births. In eight separate districts of Estonia the heterozygote frequencies
      differed significantly (p = 0.0369), with the highest incidence (1:36) on the
      Baltic Sea islands and western coastal region and with the lowest in south
      eastern parts of Estonia.

PMID- 9575454
TI  - Neonatal screening for congenital hypothyroidism in Estonia.
AB  - Screening for congenital hypothyroidism was carried out by measuring thyroid
      stimulating hormone (TSH) on dried blood spots (mean + 2SD cut off value 12
      microU/ml) by fluoroimmunoassay using DELFIA kits. A total of 20,021 infants were
      screened, and seven cases with congenital hypothyroidism were detected, giving an
      incidence of congenital hypothyroidism of 1:2860 (female:male ratio 6:1). In four
      of seven infants with congenital hypothyroidism (57%) the mother also had thyroid
      disease, supporting the importance of genetic factors as a cause of congenital
      hypothyroidism. Transient hyperthyrotropinaemia occurred in 654 infants (recall
      rate 3.3%). There was a significant association of transient
      hyperthyrotropinaemia only with cardiac failure at birth or caesarean section (p
      < 0.01). Family studies showed no predisposition to thyroid diseases associated
      with a transient increase of TSH.

PMID- 9575455
TI  - Development of the phenylketonuria screening programme in Estonia.
AB  - OBJECTIVE: To develop the phenylketonuria (PKU) screening programme in Estonia.
      METHOD: All data about patients with PKU, born during 1980-92, were documented to
      establish its prevalence at birth in Estonia. Newborn screening for the diagnosis
      and treatment of PKU was started in Estonia in 1993 and the prevalence at birth
      established by screening. Phenylalanine was determined from filter paper blood by
      a modified fluorometric method based on enhancement of the fluorescence of a
      phenylalanine-ninhydrin reaction product by L-leucyl-L-alanine. RESULTS: During
      three years (1993-5) 36,074 newborns (85% of the total) were screened for PKU.
      PKU was diagnosed in six cases during the first four to six weeks of life. All
      investigated cases could be classified as classical PKU. No cases of mild forms
      of hyperphenylalaninaemia were diagnosed. The retrospective study showed an
      average incidence of PKU of 1 in 8090, the prospective study identified a
      comparable incidence of 1 in 6010 live births. CONCLUSION: The prevalence at
      birth of classic PKU in Estonia is higher than the average in Europe and similar
      to that of some eastern and middle European countries.

PMID- 9575456
TI  - Compound heterozygosity Hb S/Hb Hope (beta 136 Gly-->Asp): a pitfall in the
      newborn screening for sickle cell disease.
AB  - The presence of Hb Hope associated with Hb S may represent a pitfall (false
      positive) in the neonatal detection of sickle cell disease by two of the most
      widely used analytical methods in screening programmes-isoelectric focusing (IEF)
      and high performance liquid chromatography (HPLC). This example illustrates the
      need to improve analytical strategies to avoid unnecessary anxiety and summoning
      of families often from a cultural background in which testing of the father is
      difficult to obtain. It is suggested that using two independent HPLC procedures
      might improve the specificity of the screening strategies. Additionally, simple
      procedures for detection of the most common mutations of the beta globin gene of
      DNA extracted from dried blood specimens could be easily developed for the
      control of abnormal samples. These procedures could be introduced into the
      analytical strategy.

PMID- 9575457
TI  - Prevalence and molecular basis of alpha thalassaemia in British South Asians.
AB  - OBJECTIVES: To determine the prevalence and molecular basis of alpha thalassaemia
      in the British South Asian population, and the implications for genetic screening
      for haemoglobin disorders. METHODS: 397 South Asian Subjects were screened for
      haemoglobinopathy with measurement of bull blood count, haemoglobin
      electrophoresis, haemoglobin A2 quantification, and plasma ferritin
      determination. alpha Globin gene mapping was successfully performed on 266 stored
      buffy coat samples using a Southern blot technique after hybridisation with Bg/II
      and BamHI. RESULTS: Of the 266 subjects in whom gene mapping was performed, 28
      had a single alpha+ thalassaemia deletion and one was homozygous for this
      deletion (gene frequency 0.056). Half of the heterozygotes had normal mean cell
      haemoglobin (MCH) values. A further 16 subjects had probable non-deletional
      alpha+ thalassaemia. None had alpha 0 thalassaemia. CONCLUSIONS: alpha
      Thalassaemia is by far the commonest haemoglobinopathy in British South Asian
      subjects, but is not a cause of serious genetic risk. Screening and counselling
      should focus on subjects with more marked red cell hypochromia (MCH < 25 pg),
      thus concentrating resources on subjects of different ethnic origins who may
      carry the alpha 0 thalassaemia gene.

PMID- 9575458
TI  - Hereditary haemochromatosis mutation frequencies in the general population.
AB  - OBJECTIVES: This study aims to expand our knowledge of the general population
      frequency of two mutations, C282Y and H63D, identified in the candidate gene for
      hereditary haemochromatosis, and to determine whether the testing can be
      performed using routinely obtained cheek-brush (buccal) samples. SETTING: Banked
      buccal lysate samples, randomised and coded for anonymity, from a cohort of
      couples who underwent prenatal cystic fibrosis screening in Maine. METHODS: A
      multiplex ARMS test was performed on buccal cell lysates to identify the two
      mutations. RESULTS: Genotype frequencies found among the 1001 subjects studied
      (502 women, 499 men) were: seven C282Y homozygotes, 22 C282Y/H63D compound
      heterozygotes, 97 C282Y heterozygotes, 17 H63D homozygotes, 246 H63D
      heterozygotes, and 612 individuals with no detectable mutation. The allele
      frequencies for C282Y and H63D were 0.066 and 0.151, respectively. CONCLUSIONS:
      Observed genotype frequencies in Maine are consistent with expectations and with
      consensus data from five smaller studies. Combined mutational analysis data
      indicate that homozygosity for C282Y (the genotype found in about 85% of subjects
      with diagnosed hereditary haemochromatosis) occurs in 51 per 10,000 white
      subjects of northern European heritage; the corresponding total hereditary
      haemochromatosis prevalence of about 60 per 10,000 is consistent with previous
      estimates. The study also confirms that H63D would not be useful in general
      population screening for hereditary haemochromatosis.

PMID- 9575459
TI  - Evaluation of the effect of breast cancer screening by record linkage with the
      cancer registry, The Netherlands.
AB  - OBJECTIVE: To evaluate the effect of a breast cancer screening programme by
      record linkage with the cancer registry. SETTING: Breast cancer screening
      programme in mid- and southern Limburg, the Netherlands. METHODS: The data files
      of the breast cancer screening programme and the Maastricht Cancer Registry were
      linked in order to evaluate the effect of breast cancer screening. Only the first
      primary breast tumour was included in the evaluation. RESULTS: From 1990 until
      1995 90 001 women participated in the first round of the breast cancer screening
      programme and 64 637 in subsequent rounds. After the introduction of screening
      the annual number of breast cancer diagnoses increased by almost 50%. The
      incidence decreased to previous levels after completion of the first screening
      round. Record linkage detected 219 interval cancers (within two and a half years
      of a screening), a proportionate incidence of 31% in the first year and 60% in
      the second year of the two-year interval between screenings. The incidence of
      node positive breast cancer was 1% lower in 1994 and 15% lower in 1995 than the
      incidence in the period 1987-90. CONCLUSIONS: Evaluation of the effect of breast
      cancer screening in the Netherlands can be performed using routinely available
      cancer registry data. The results of this evaluation seem promising, but further
      studies are necessary to find ways to reduce the incidence of interval cancer.

PMID- 9575460
TI  - Breast cancer in East Anglia: the impact of the breast screening programme on
      stage at diagnosis.
AB  - OBJECTIVES: To assess the impact of the National Health Service breast screening
      programme on overall and stage-specific incidence of breast cancer in East
      Anglia; also, to predict the magnitude of the screening induced reduction in
      breast cancer mortality. SETTING: Women resident in East Anglia aged 50-69,
      diagnosed between 1976 and 1995. METHODS: Comparison of numbers and incidence of
      breast cancer by age, stage, and mode of detection; investigation of relative
      contributions of advanced (stages II, III, and IV) cancers to total incidence by
      detection mode; estimation of the reduction in advanced cancer incidence.
      RESULTS: There has been a large increase in early stage incidence in the age
      group 50-64 targeted by the screening programme. By 1995, the estimated decrease
      in advanced cancer incidence was between 7 and 19%. In 1995, of all breast
      cancers arising in the age group 50-69 years, 33% were screen detected, 27% were
      interval cancers, 15% were in non-attenders, 9% were in lapsed attenders, 7%
      occurred before invitation, and 4% arose in women outside the birth year range
      for invitation. Of the advanced cancers diagnosed in 1995, 31% were interval
      cancers, 20% were screen detected, 19% were in non-attenders, 12% were in lapsed
      attenders, 8% occurred before invitation, and 4% presented in women outside the
      birth year range for invitation. CONCLUSIONS: Screening has brought about a large
      increase in detection of early stage cancers. This increase has not yet been
      fully matched by a corresponding deficit in advanced cancers, possibly because
      the full effect of screening has not yet been achieved. Reducing the proportion
      of interval cancers is necessary to increase the effect of screening on
      mortality.

PMID- 9575461
TI  - Can postal prompts from general practitioners improve the uptake of breast
      screening? A randomised controlled trial in one east London general practice.
AB  - OBJECTIVE: To determine the effect on the uptake of breast screening of a
      personalized letter from the general practitioner recommending mammography, sent
      to coincide with an invitation from the NHS breast screening programme. DESIGN:
      Randomised control trial with stratification of prognostic variables. SETTING: A
      group practice in Hackney, east London. SUBJECTS: 473 women invited for breast
      screening by the City and East London Breast Screening Service. OUTCOME MEASURE:
      Attendance for mammography. RESULTS: All women in the randomised trial were
      followed up; 134 of 236 (57%) randomly allocated to receive the prompting letter
      attended for mammography compared with 120 of 234 (51%) controls This difference
      was not significant (chi 2 = 1.43, p = 0.23) CONCLUSION: Personal recommendation
      by a letter prompting attendance for mammography from the general practitioner
      known best to women due to be screened did not improve uptake of breast screening
      in this east London practice. Other strategies are needed to increase uptake of
      mammography in inner cities.

PMID- 9575462
TI  - Antenatal screening for hepatitis B.

PMID- 9575463
TI  - Antenatal screening for hepatitis B.

PMID- 9575464
TI  - Psychological aspects of Turner syndrome.
AB  - Turner syndrome (TS) is a sex-chromosome disorder, occurring in 1 in 2500 female
      births. The principal features of TS are short stature and dysfunctional gonads,
      resulting in a lack of sex hormones, incomplete pubertal development and impaired
      fertility. The aim of this paper is to review the literature on the psychological
      effects of TS. The main areas covered relate to well-being and psychopathology,
      self-esteem, social functioning, gender identity, partner relations and sexual
      functioning, coping, family aspects and clinical aspects of cognitive impairment.
      Research on the psychological effects of medical intervention is described, and
      the methods used for psychological and educational support are presented.
      Finally, methodological issues are discussed and areas for future research are
      proposed.

PMID- 9575465
TI  - Parenthood motives in IVF-mothers.
AB  - This is an exploratory study to answer two questions: (1) does in-vitro
      fertilization (IVF)-mothers' motivation for parenthood differ from the naturally
      conceiving mothers' motivation for parenthood? and (2) are IVF-mothers'
      parenthood motives correlated with their adjustment to parenthood (in the same
      way as they are for naturally conceiving mothers)? The study sample consisted of
      31 mothers with a 24-30 month old, single-born child conceived by homologous IVF
      and a comparison group of 31 mothers with a naturally conceived child. Self
      rating questionnaires were used. Overall, the parenthood motivation pattern was
      quite similar for IVF-mothers and mothers by natural conception. However,
      'identity', 'motherhood' and 'social control' were significantly more important
      motives for IVF-mothers than for the naturally conceiving mothers. The two former
      motives remained more important for IVF-mothers when findings were adjusted for
      the influence of the mothers' age and educational level. Possible explanations
      for these findings refer to the infertility history. Overall, few correlations
      between parenthood motives and the adjustment to parenthood were significant,
      both for the IVF-mothers and for the mothers by natural conception. Further
      (hypothesis-testing) research is needed to support these findings.

PMID- 9575466
TI  - A prospective study of the impact of psychosocial and lifestyle variables on
      pregnancy complications.
AB  - This prospective study examines the influence of maternal stress, social support
      and lifestyle variables reported over the course of pregnancy on subsequent
      gestational and intrapartum complications. Demographic and biomedical factors
      were also studied. One hundred and two women were followed on a monthly basis
      beginning in the third month of pregnancy. Measures of daily stress (hassles),
      state-anxiety (STAI-state) and pregnancy-specific stress were taken monthly.
      Pregnancy progress and lifestyle behaviors such as smoking, caffeine and alcohol
      intake were assessed by trimester. One month following delivery, a telephone
      interview was conducted to inquire about the labor/delivery and infant status.
      Sixty-three per cent of the women experienced a pregnancy complication. Three
      groups consisting of women who experienced gestational complications, intrapartum
      complications only, and no complications were formed. Women who subsequently
      experienced gestational complications reported over the course of their pregnancy
      higher levels of state-anxiety, daily hassles and pregnancy-specific stress
      beginning in the third month of pregnancy. Women who experienced complications
      during the intrapartum period only reported higher daily hassles during pregnancy
      and consumed more caffeinated beverages compared to the other groups. Primiparous
      women were more likely to experience gestational and/or intrapartum complications
      than multiparous women. These findings support a role for psychosocial variables
      in pregnancy complications. The results indicate that certain psychosocial and
      lifestyle variables may be differentially associated with complications occurring
      at various phases of pregnancy.

PMID- 9575467
TI  - Contents of childbirth-related fear among couples wishing the partner's presence
      at delivery.
AB  - In order to explore the contents of childbirth-related fears, a survey was
      carried out among 216 pairs of prospective parents who opted for the presence of
      the partner at delivery. Each couple took part in a three-class parentcraft
      course during the third trimester. During the first antenatal class, couples were
      asked to fill in a questionnaire with inquiries about specific contents of fear
      they might have in relation to pregnancy, childbirth and relationship with their
      partner after childbirth. Each item of the questionnaire called for an answer
      from a five-grade scale of fear such as 'absolutely not', 'slightly', 'quite',
      'quite strongly' and 'very much'. Their worries were ranked according to the
      weighted average of the frequency of positive answers. More than 80% of both men
      and women had some fears relating to childbirth. Women were most worried about,
      in order of significance, having a malformed or injured baby, assisted or
      operative delivery, being lonely in a strange environment, doing something wrong,
      and facing the uncertainties of how the delivery was going to happen. The wife
      having severe pain and suffering, operative delivery, fetal birth injuries,
      helplessness, powerlessness and the wife's death in childbirth were the most
      significant subjects of men's fears. Eighty per cent of women and 76% of men felt
      that the presence of the partner at delivery would have no adverse effect on
      their future personal relationship.

PMID- 9575468
TI  - Parental behavior after perinatal death: twelve years of observations.
AB  - Perinatal death is a tragic occurrence, and parents vary in their needs and how
      they express grief. This prospective study describes choices parents made
      regarding contact with their baby following stillbirth or immediate neonatal
      death. Between 1 January 1979 and 1 March 1991, 808 consecutive families were
      enrolled in the Perinatal Mortality Counseling Program at the University of
      Florida. Following perinatal death, most parents wanted contact with their baby
      to personalize the event, information about the death and follow-up from their
      health care providers. However, no option was chosen by all parents. This large
      study strongly supports offering choices to all parents. Providers should neither
      bias parents nor make presumptions that would limit parental choices.

PMID- 9575469
TI  - Oxytocin, prolactin, milk production and their relationship with personality
      traits in women after vaginal delivery or Cesarean section.
AB  - The aim of the present study was to investigate if personality profiles
      reflecting anxiety and social interaction of mothers who delivered by Cesarean
      section (CS) or by the vaginal route (VD) differed in early postpartum and to
      investigate whether these personality traits were correlated with hormonal data.
      Seventeen women delivered by emergency CS and 20 by the vaginal route were
      selected for this study. The amount of milk transferred to the baby was measured.
      Blood samples were collected during the second breast-feeding on the second day
      after delivery. The samples were analysed for oxytocin and prolactin. After
      breastfeeding, the mothers were asked to fill in the personality inventory,
      Karolinska Scales of Personality (KSP). The scores were compared between the two
      groups and with a normative group of women. Each scale on the personality
      inventory was correlated with hormonal parameters. The KSP showed significant
      differences between the delivered mothers and the normative group in variables
      related to anxiety and socialization. The VD mothers deviated more than the CS
      mothers from the normative group. Correlations with hormonal data indicated that
      anxiety was inversely related with basal levels of oxytocin and prolactin in the
      CS mothers, whereas the pulsatility of oxytocin was related to social
      desirability in both groups. Social desirability and oxytocin pulsativity were
      also correlated with the amount of milk transferred from the mother to the baby.
      The correlations indicate that central oxytocin, as reflected by basal plasma
      levels and patterns, may be involved in behavioral adaptations to the maternal
      role.

PMID- 9575471
TI  - Copper and zinc determination in plasma and corpuscular components of peripheral
      blood of patients with preterminal and terminal renal failure.
AB  - Homeostasis of trace elements is an essential condition for the activation and
      regulation of metabolic processes. Its disturbance results in clinical symptoms.
      Since most trace elements are eliminated via the renal system, their balance is
      disturbed in patients with preterminal or terminal renal insufficiency. However,
      only a low percentage of trace elements can be detected in plasma, so that the
      intracellular determination of trace elements in corpuscular components in
      peripheral blood cells might be of interest. After blood was taken from the shunt
      vessel, the cells were isolated by density gradient centrifugation media. The
      concentrations of the trace elements copper and zinc in peripheral blood cells
      and plasma were determined by means of electrothermal atomic absorption
      spectrometry. Compared with healthy blood donors, in patients with preterminal
      and terminal renal insufficiency concentrations in plasma and peripheral blood
      cells were altered but in different directions. In renal insufficiency copper
      concentration in plasma (median: 13.9 mumol/l) and erythrocytes (median: 0.8
      mumol/ 10(9) cells) was normal and in the lower reference range, respectively,
      whereas copper concentration in the platelets was elevated (median of 20 mumol/1
      10(9) cells). As regards zinc, patients with preterminal and terminal renal
      insufficiency both suffered from low values in plasma (median: 8.6 mumol/l). In
      contrast, the concentration in erythrocytes and thrombocytes was elevated
      (medians: 17.9 mumol/10(9) cells and 14.0 mumol/10(9) cells, respectively)). In
      conclusion, the intracellular determination of the trace elements copper and zinc
      is of value for diagnosis and monitoring of the trace element deficiency status.

PMID- 9575470
TI  - Maternal selenium status influences the concentration and binding pattern of zinc
      in human milk.
AB  - To study the health effects of high dietary maternal selenium intake breast milk,
      blood and toe-nails were collected from 143 women (20-24 days of lactation)
      living in Venezuelan states of Yaracuy and Portuguesa. Depending on the regional
      selenium intake level three regions were defined within the total range of 90-980
      microgram per day. The samples were analyzed by means of INAA for the
      determination of trace elements, including selenium and zinc. The significant
      inverse correlation between Se and Zn in breast milk found in former studies was
      confirmed. Investigation of the Zn-binding pattern in milk whey was carried out
      by an on-line combination HPLC (SEC) for protein separation and ICP-AES for
      element detection. Six Zn-binding compounds including citrate were detected. A
      highly significant negative correlation was found between the citrate, which is
      the main low-molecular Zn-binding compound, and the maternal daily selenium
      intake. We determined that the decrease in zinc concentration is due to a
      decrease in the citrate level, which depends on the selenium concentration in
      breast milk. The selenium concentration in breast milk is, in turn, proportional
      to the dietary intake. In addition, significant changes in the UV- and Zn
      profiles were observed in the milk whey with the highest selenium content,
      indicating that above a certain maternal intake level substantial changes in the
      composition of mammary secretory cells occur. This effect can be of interest for
      estimation of the safe dietary intake level of selenium.

PMID- 9575472
TI  - Concentrations of copper, zinc and selenium in brain and kidney of second
      trimester fetuses and infants.
AB  - The concentrations of copper (Cu), zinc (Zn) and selenium (Se) in the brain and
      kidneys of second trimester fetuses (abortion cases) and infants (deceased before
      three months of age) were determined. Concentrations of Cu in brain, 0.31-1.6
      mg/kg wet weight, increased with age, and were, on the average, three times
      higher in the brains of infants than of fetuses. In kidneys, Cu concentrations
      ranged between 0.34 and 2.9 mg/kg, and increased with age after birth.
      Concentrations of Zn in the brain decreased significantly with age in the
      fetuses, from about 7 mg/kg at post-conceptional week 12 to less than 5 mg/kg at
      week 20, but increased again postnatally. In kidneys, Zn concentrations (12-37
      mg/kg) increased in parallel with the increase in tissue density. Concentrations
      of Se in brain, 0.072-0.14 mg/kg, decreased with age in the fetuses, but
      increased with age postnatally. Kidney Se concentrations (0.16-0.55 mg/kg) did
      not change significantly with age during the fetal period, but increased about
      2.5 times during the postnatal period. There was a significant association
      between the concentrations (on molar basis) of Zn and Cu in kidneys, but not in
      brain. There was no correlation between the concentrations of Cu, Zn or Se and
      those of mercury, cadmium and lead, previously determined in the same samples,
      with the exception of mercury and Se in kidneys.

PMID- 9575473
TI  - Fish oil effects on tissular fatty acids and plasma lipid peroxidation in zinc
      deficient rats.
AB  - Zinc has been reported to play a key role in lipid metabolism as well as in
      defences against oxidative stress. The aim of this work was to investigate the
      fatty acid distribution (plasma, heart, kidney, liver) and peroxidation (plasma)
      in zinc-deficient rats fed with n-6 fatty acids (10% corn oil) or n3 fatty acid
      fish oil (10% Maxepa). Zinc deficiency led to a decreased tissular and plasma n
      6/n-3 ratio both in triglycerides and phospholipids. This effect was more marked
      in the Maxepa group than in the corn oil group. In plasma, the TBARs/TG + PL
      ratio was significantly enhanced in zinc-deficient animals, especially in rats
      receiving Maxepa. With regard to these results, zinc deficiency could appear as
      an aggravating factor of oxidative risk when associated with a n-3 fatty acid
      rich diet. This work draws attention to the harmful oxidative risk associated
      with patients' intake of fish oil concentrate, without taking into account their
      antioxidant dietary intakes and status.

PMID- 9575475
TI  - Mechanisms of absorption of As2O5 from rat small intestine: the effect of
      different parameters.
AB  - The main purpose of this research was to study the effects of water movement on
      arsenic absorption. In order to appreciate and measure the interaction between
      these two variables we investigated the perfusion of isotonic and hypotonic
      buffers (containing 3.2 microgram/ml As2 O5 into rat small intestines. The As (V)
      depended on osmolarity sensitive. This implied the presence of a saturable uptake
      kinetic mechanism and suggested the participation of some kind of carrier
      mediated transport system. An increase in arsenate absorption and its
      accumulation in organs was detected in the presence of an Na+ gradient. The same
      technique, combining isotonic buffers with different pH values and buffers
      containing valinomycin, was used in order to study the effects of intraluminal pH
      on membrane potential. A significant decrease in arsenic levels and As(V)
      absorption in organs was detected as a result of an increase in the pH. This
      influence of pH on the As(V) absorption mechanism indicated dependence on a
      proton (H+) gradient. An inside negative potassium potential induced by
      valinomycin increased significantly the uptake of arsenate, suggesting an
      electrogenic transport of arsenate. In conclusion, the As(V) might be absorbed
      from the small intestine through a carrier-mediated mechanism, which would depend
      on the Na+(-) and H+(-)gradients and the membrane potential differential from
      both sides of the intestinal epithelial cells.

PMID- 9575474
TI  - Trace elements in pleural effusions.
AB  - When the secretion of pleural fluids exceeds their resorption, liquid (pleural
      effusion ) will accumulate between the visceral and parietal pleura. Pleural
      effusions derived from the liquid components of blood are expected to contain
      trace elements and may, as a sink for trace elements, deprive the body of needed
      essential elements upon their removal by medical intervention. Consequently,
      patients may be at risk of drifting into trace-element deficiencies. Because the
      literature is almost devoid of data about trace elements in effusions, the
      concentrations of 14 trace elements (Ba, Ca, Cd, Co, Cs, Cu, Mg, Mn, Mo, Pb, Rb,
      Sn, Sr, Zn) were determined simultaneously by inductively-coupled argon-plasma
      mass spectrometry (ICP-MS) in effusions from 17 patients. The median values for
      the concentrations of Rb (209 microgram/kg, range 104-334 microgram/kg) and Cs
      (1.5 micrograms/kg, range 0.8-2.4 microgram/kg) in the effusions were almost the
      same as in the sera. The concentrations of Mg (range 15-22 mg/kg), Ca range 52-91
      mg/kg), Sr (range 12-37 micrograms/kg), and Ba (range 1.4-18.2 micrograms/kg)
      were consistently lower in the effusions than in the sera by 18% for Mg, 26% Ca
      14% for Sr, and 88% for Ba (percentages based on median in serum as 100%). The
      concentrations of the essential trace elements Co (range 0.16-0.5 microgram/kg),
      Cu (130-902 micrograms/kg), Mn (0.2-2.2 micrograms/kg), Mo (0.4-1.5
      micrograms/kg), Sn (0.4-1.2 micrograms/kg), and Zn (27-1931 micrograms/kg) in the
      effusions are generally lower (25-55% based on median) than in the corresponding
      sera, although a few effusions have higher concentrations of Co, Mn Mo, or Zn
      than in the sera. The concentrations of Cd (range 0.2-0.5 microgram/kg) in the
      effusions were approximately the same as in the sera for three patients,
      considerably lower than in the sera for four patients, and considerably higher
      for three patients. The concentrations for lead (range 0.6-45 micrograms/kg) in
      the effusions were generally much higher than in the sera. The effusions were not
      significantly contaminated with lead-rich erythrocytes. The concentrations of Ca,
      Cu, and Zn in the effusions correlated positively with the protein concentrations
      in the effusions. One kilogram of the effusions contain from 10-30% of the trace
      elements present in the entire volume of serum in circulation.

PMID- 9575476
TI  - Relationship of calcium, magnesium, zinc and copper concentrations in the
      arterial wall and serum in atherosclerosis obliterans and aneurysm.
AB  - Changes in copper concentration in the arterial wall are important because of
      cross-linkage formation in collagen and elastin. The breakdown of the elastic
      layer is characteristic for aneurysm and is affected by the abnormalities in
      copper metabolism. This study was undertaken to evaluate Ca, Mg, Zn and Cu
      concentrations and their relationships in the arterial wall, serum and calcified
      plaque in atherosclerosis obliterans (AO) and abdominal aortic aneurysm (AA).
      Samples of the aorta wall were obtained at the endarterectomy in AO and the
      vascular reconstruction in AA. Elements were determined by means of atomic
      absorption spectrometry. Serum concentrations of Zn and Cu were higher and that
      of Ca lower in AO as compared to AA and the controls. Arterial concentrations of
      Zn, Cu and Mg were higher in AO as compared to AA. The ratios of element
      concentrations in serum (Ca/Mg, Ca/Zn and Mg/Cu) were higher in serum in AA than
      in AO. Positive correlations were calculated for Ca and Mg (r > or = 0.74), Ca
      and Zn (r > or = 0.73), Mg and Zn (r > or = 0.90) in the arterial wall in AO and
      AA. Low but significant correlation was calculated for Cu concentrations between
      serum and the arterial wall in AA (r = 0.43). Concentrations of Ca, Mg, Zn and Cu
      were higher in plaque than in the surrounding tissue. The results indicate
      differences in arterial and serum concentrations of Ca, Mg, Zn and Cu between AO
      and AA and the accumulation of these elements in the plaque rather than in the
      surrounding vascular tissue.

PMID- 9575477
TI  - Effects of single and repeated administrations of Toki-shakuyaku-san on the
      concentrations of brain neurotransmitters in mice.
AB  - The amounts of monoamine-related substances (NE, MHPG, DA, DOPAC, HVA, 5-HT, and
      5-HIAA and acetylcholine (ACh) in the cerebral cortex, corpus striatum and
      hippocampus of mice treated orally with a powdered extract of Toki-shakuyaku-san
      (TSS) were measured using the HPLC-ECD method. Single administration of TSS at 50
      mg/kg decreased the content of NE in the hippocampus, but increased the contents
      of DA, DOPAC and HVA. Single administration of TSS at 50 mg/kg increased the
      contents of DA and HVA in the cerebral cortex and those of DA, DOPAC and HVA in
      the hippocampus, but decreased the content of NE. Repeated administration (twice
      a day, for 14 days) of TSS at 50 mg/kg increased the contents of DA, DOPAC and 5
      HIAA in the cerebral cortex, while 500 mg/kg increased the contents of NE, MHPG,
      DOPAC, 5-HT and 5-HIAA in the cerebral cortex, and the NE and DA in the corpus
      striatum. With regard to ACh content, single and repeated administrations of TSS
      at 50 and 500 mg/kg had no influence in the three regions of mouse brain. These
      results suggest that single administration of TSS stimulates the function of the
      dopaminergic nervous system in the hippocampus in mice and inhabits the function
      of the adrenergic nervous system, and that repeated administration of TSS
      stimulates the function of the adrenergic, dopaminergic and serotonergic nervous
      systems in the cerebral cortex. TSS, however, did not show any influence on the
      brain ACh content in mice.

PMID- 9575478
TI  - Effects of Saiko-ka-ryukotsu-borei-to on irritable characteristics in El mice.
AB  - In the present study, we attempted to characterize the circadian rhythm of
      locomotor activity of El mice and to examine the duration of sodium pentobarbital
      induced sleep during the light and dark periods. The effect of Saiko-ka-ryukotsu
      borei-to, a representative Kampo medicine used for treating insomnia, was studied
      on the locomotor activity and on the duration of sodium pentobarbital-induced
      sleep in El mice. The spontaneous locomotor activity of El mice during the dark
      period was not so different from that of ddY mice, whereas the activity during
      the light period was significantly higher in the El mice, and the duration of
      sodium pentobarbital-induced sleep of El mice was very short during the light
      period, nearly equal to that during the dark period. The administration of Saiko
      ka-ryukotsu-borei-to caused marked reduction in the locomotor activity during the
      light period, and dose-dependent prolongation in the duration of sodium
      pentobarbital-induced sleep time during the light period, but that during the
      dark period was unaffected. These findings suggest that the El mouse is a model
      with a tendency to be easily excitable during the light period compared to ddY
      mice. Furthermore, it was confirmed that Saiko-ka-ryukotsu-borei-to reduced the
      excitation in El mice and might be useful against sleep disorder due to
      excitation.

PMID- 9575479
TI  - Increase in monoamine levels caused by emotional stress in mice brain regions is
      attenuated by Saiko-ka-ryukotsu-borei-to.
AB  - The effect of Saiko-ka-ryukotsu-borei-to (SRBT) on the stress-induced increase of
      monoamines in brain regions was investigated in three mouse emotional stress
      models. Dopamine (DA) and 3,4-dihydroxy-phenyl acetic acid (DOPAC) contents were
      elevated significantly by electric shock stress, psychological stress and
      conditioned fear stress in thalamus, hypothalamus and amygdala. The DA and DOPAC
      levels were decreased by preadministration of SRBT (600 mg/kg, p.o.) in the last
      two models, but were not altered in electric shock stress. Therefore, this
      compound seems to be effective in stress involving emotional factors. These
      results indicate that SRBT affects the brain monoamine neurons leading to
      psychological change in mice.

PMID- 9575480
TI  - Protective effects of Hange-shashin-to on water-immersion restraint stress
      induced gastric ulcers.
AB  - Hange-shashin-to (HST) is a traditional Chinese herbal prescription (Banxia
      Xiexin Tang) which has long been used in the therapy of gastric functional
      disorders. In this report, the effect of HST extract on water-immersion restraint
      stress-induced gastric ulcer based on the changes in gastric mucin content and
      the variations of monoamine contents in hypothalamus were investigated. Ulcer
      index was microscopically measured by the sum total of the lengths of ulcers in
      glandular stomach. Gastric mucin content was determined by a PAS-staining methods
      and the monoamine contents were detected by HPLC-ECD method. HST extract was
      orally administered at 1, 2 and 3 g/kg for three consecutive days before stress
      exposure. Water-immersion restraint stress decreased the mucin content and
      produced gastric ulcers in a restraint time-dependent manner. Pretreatment with
      HST extract markedly inhibited the reduction of gastric mucin content and the
      development of gastric ulcer with significant differences (p < or = 0.01). The
      remarkable decrease of NE and 5-HT contents but prominent increases of MHPG and 5
      HIAA contents were observed in hypothalamus after water-immersion restraint
      stress (p < or = 0.01). Those changes in monoamine contests in hypothalamus were
      also significantly inhibited by the pretreatment with HST extract at higher
      dosage (p < or = 0.05). These results indicate that the changes in gastric mucin
      content and the variation of monoamines in hypothalamus relate to the
      pathogenesis of water-immersion restraint stress-induced gastric ulcers, and it
      is suggested that the prophylactic effects of HST extract on stress induced
      gastric ulcers may be associated with an increase in gastric mucin content,
      although the prevention of HST extract on the extraordinary changes in monoamine
      contents in hypothalamus due to stress cannot be ruled out.

PMID- 9575481
TI  - Effects of Toki-shakuyaku-san on electric footshock stress in ovariectomized
      mice.
AB  - In the present study, ovariectomized mice were exposed to electric footshock
      stress for 7 days, and the duration of sodium pentobarbital-induced sleep was
      measured on the day following the last stress exposure. In ovariectomized mice,
      the duration of sodium pentobarbital-induced sleep before exposure to stress did
      not differ markedly from that in the sham-operation group. After exposure to
      stress, however, the duration of sodium pentobarbital-induced sleep in
      ovariectomized mice was shortened significantly, compared to the ovariectomized
      mice without stress. When the effect of Toki-shakuyaku-san on the stress-induced
      shortening of sleep time was studied, it was found that the shortening of the
      sleep time was suppressed by treatment with Toki-shakuyaku-san. In ovariectomized
      mice, the increase in hypothalamic noradrenaline (NA) turnover in response to
      stress was significantly greater than that in mice with intact ovaries. The
      stress-induced enhancement of NA turnover was suppressed significantly by Toki
      shakuyaku-san in a dose-dependent manner, beginning with a low dose level. When
      effect of 17Beta-estradiol on the stress induced-shortening of sleep time was
      examined in ovariectomized mice, by high doses of 17Beta-estradiol the shortening
      of the sleep time was prolonged. A major difference between 17Beta-estradiol and
      Toki-shakuyaku-san was the marked uterine weight gain observed following 17Beta
      estradiol treatment despite no effect of Toki-shakuyaku-san on uterine weight.
      The results in this study suggest that Toki-shakuyaku-san may reduce menopausal
      symptoms by a mechanism different from that of estrogen.

PMID- 9575482
TI  - Effects of Hochu-ekki-to, Yoku-kan-san and Saiko-ka-ryukotsu-borei-to on
      behavioral despair and acetic acid-induced writhing in mice.
AB  - Effects of the Kampo (Chinese herbal) medicines Hochu-ekki-to Yoku-kan-san and
      Saiko-ka-ryukotsu-borei-to, on behavioral despair and acetic acid-induced
      writhing were studied in mice. The Kampo medicines were administered for 14
      consecutive days in the drinking water. In a behavioral despair study, mice were
      placed in a water tank containing a water wheel from which there was no escape
      for 15 min and the number of wheel rotations was counted as escape attempts. In
      accord with previous studies, imipramine (10 mg/kg i.p.) given daily for 3 days
      10 min before testing markedly increased the number of wheel rotations. Hochu
      ekki-to (60, 150 and 300 mg/kg/day) similarly increased the number of wheel
      rotations but the effect was not dose-dependent. Yoku-kan-san markedly increased
      the number of wheel rotations at lower doses (60 and 150 mg/kg/day), but
      decreased the number at the highest dose (300 mg/kg/day). Saiko-ka-ryukotsu-borei
      to also increased the number of wheel rotations at the lowest does (60 mg/kg/day)
      but decreased the number at higher doses (150 and 300 mg/kg/day). In an
      antinociception study, all these Kampo medicines reduced the number of acetic
      acid-induced writhings, although the effect of Saiko-ka-ryukotsu-borei-to were
      not dose-dependent. These results suggests that these Kampo medicines may have
      antidepressive and antinociceptive properties.

PMID- 9575483
TI  - Central action of 9-methyl-7-bromoeudistomin D (MBED), a derivative of eudistomin
      D isolated from Eudistoma olivaceum.
AB  - The behavioral responses of mice following intracerebroventricular (i.c.v.)
      injection of 9-methyl-7-bromoeudistomin D (MBED) were studied. Head-twitches were
      produced 20-90 min after the injection of 2, 20 and 200 nmol/mouse but such
      twitches were not significantly induced by caffeine (1000 nmol/mouse). The
      locomotor activity, as assessed by the Animex autometer, increased 0-120 min
      after the injection with doses of 2, 20 and 200 nmol/mouse, whereas a large dose
      of caffeine (500 nmol/mouse also increased the activity counts. Simultaneous
      injection of picrotoxin (3 mg/kg, s.c.) and MBED (50, 100 and 200 nmol/mouse)
      produced clonic and tonic extensive convulsions, but caffeine (1000 nmol/mouse)
      in combination with picrotoxin did not cause any type of convulsion.

PMID- 9575484
TI  - Preventive effects of various ginseng saponins on the development of copulatory
      disorder induced by prolonged individual housing in male mice.
AB  - Recently, we found that virtually all male mice failed to display copulatory
      behavior following prolonged individual housing. The present study was conducted
      to investigate whether or not ginseng saponin components prevent the development
      of this copulatory disorder. ICR male mice were housed individually for 5 weeks
      after weaning, followed by a 10-min encounter with an estrous female mouse. The
      following constituents of red ginseng powder were administered intraperitoneally
      once per day throughout the individual housing period: crude ginseng saponins and
      pure ginsenoside Rb1, Rb2, Rg1, and Ro. Three elements of copulatory behavior
      (mounting, intromission and penis licking) were determined. Following prolonged
      individual housing only one mouse in the vehicle-treated group displayed
      mounting. Chronic treatment with crude ginseng saponins (25, 50 and 100 mg/kg)
      significantly lessened the severity of copulatory disorder in a dose-dependent
      manner. Ginsenoside Rg1 (2.5, 5 and 10 mg/kg) also resulted in a significantly
      higher incidence of copulatory behavior as compared to the individually housed
      vehicle-treated group, whereas ginsenoside Rb1, Rb2 and Ro were ineffective. This
      evidence indicates that ginsenoside Rg1 is one of the ingredients of red ginseng
      root that acts on male copulatory behavior.

PMID- 9575485
TI  - The antistress effect of majonoside-R2, a major saponin component of Vietnamese
      ginseng: neuronal mechanisms of action.
AB  - Majonoside-R2 (MR2), an ocotillol-type saponin, is a dominant saponin component
      of Vietnamese ginseng. We have investigated the effect of MR2 on behavioral and
      pathophysiological changes caused by psychological stress such as the
      communication box paradigm-induced psychological stress (CBP stress), conditioned
      fear stress and social isolation stress in laboratory animals, and elucidated the
      possible neuronal mechanisms underlying the action of this compound. MR2
      attenuated CBP stress- and conditioned fear stress-induced antinociception, had a
      protective effect against CBP stress-induced gastric lesions, and restored the
      hypnotic activity of pentobarbital decreased by CBP stress or social isolation
      stress to the level of the unstressed controls. Accumulating evidence strongly
      suggests the involvement of the central opioid, GABAA receptor and corticotropin
      releasing factor mechanisms in the effect of MR2. Here we review the antistress
      effect of Vietnamese ginseng, especially focusing on the effect of MR2 on
      psychosomatic disorders caused by psychological stress.

PMID- 9575486
TI  - Pharmacological and physiological effects of ginseng on actions induced by
      opioids and psychostimulants.
AB  - Pharmacological and physiological effects of ginseng on actions induced by
      opioids and psychostimulants are summarized. Analgesic effects of opioids, such
      as morphine and U-50, 488H, were blocked by ginseng in a nonopioid dependent
      manner. Furthermore, ginseng inhibited the tolerance to and dependence on
      morphine, and eliminated the suppressive effect of the development of morphine
      tolerance by coexposure to footshock stress, but not psychological stress. On the
      other hand, behavior sensitization (reverse tolerance to their ambulation
      accelerating effect) to morphine, methamphetamine and cocaine was also inhibited
      by ginseng. Interestingly, ginseng also inhibited the appearance of the recurrent
      phenomenon (reappearance of the sensitized state was observed at the time of
      readministration of methamphetamine and cocaine even after a 30-day
      discontinuation of drug administration) of the effect of methamphetamine and
      cocaine. The conditioned place preference of methamphetamine and cocaine was
      completely blocked by ginseng. These findings provide evidence that ginseng may
      be useful clinically for the prevention of abuse and dependence of opioids and
      psychostimulants.

PMID- 9575487
TI  - Targeting toxins to brain tumors.

PMID- 9575488
TI  - Say NO to anal fissures.

PMID- 9575490
TI  - Tuberculosis: milking the genome for drug targets and vaccines. Novartis
      Foundation Symposium: Genetics and Tuberculosis. Cape Town, South Africa, 18-20
      November 1997.

PMID- 9575489
TI  - The role of epigenetics in cancer. DNA Methylation, Imprinting and the
      Epigenetics of Cancer--an American Association for Cancer Research Special
      Conference. Las Croabas, Puerto Rico, 12-16 1997 December.

PMID- 9575491
TI  - Brushing up on immunological tolerance. Immunologic Tolerance for Immune System
      Mediated Diseases, Bethesda, MD, USA, 8 December 1997.
AB  - While nonspecific immunosuppressive agents have had major impact both on
      autoimmune disease and transplantation, the development of specific immunological
      tolerance holds great promise for the future. Studies of tolerance thus have both
      theoretical and practical implications for biology and medicine.

PMID- 9575492
TI  - Does antiperspirant use increase the risk of aluminium-related disease, including
      Alzheimer's disease?
AB  - Aluminium salts are the major constituent of many widely used antiperspirant
      products. The use of such antiperspirants has been linked with the systemic
      accumulation of aluminium and an increased risk of Alzheimer's disease. But can
      the frequent use of aluminium-based antiperspirants lead to the accumulation of
      toxic levels of aluminium? And are there measures that we can take to reduce such
      accumulation without reducing the effectiveness of antiperspirants?

PMID- 9575493
TI  - Insulin-like growth factor 2 and overgrowth: molecular biology and clinical
      implications.
AB  - The insulin-like growth factors, IGF1 and IGF2, play a fundamental role in human
      fetal growth. Of the growth disorders that involve excessive growth, many could
      be attributable to overexpression of IGF2. Because one copy of the IGF2 gene is
      silenced by genomic imprinting, several different molecular errors can double the
      number of active copies of the IGF2 gene. Although not formally demonstrated,
      each of these errors is expected to double the level of IGF2 expression. The
      nature and severity of the overgrowth might be dependent on the number and
      location of cells that carry the molecular defect.

PMID- 9575494
TI  - Soluble HLA class I molecules: biological significance and clinical implications.
AB  - Soluble class I human leukocyte antigens (sHLAs) have been detected in serum,
      sweat, lymphatic fluid, urine and cerebrospinal fluid. Their biological function
      has, however, remained a puzzle. The physiological concentration of sHLA varies
      more than tenfold depending on the phenotype of the individual, and is
      significantly upregulated in various diseases and during inflammation. This
      suggests that sHLAs might serve as a marker of pathological changes. Recent
      experiments have shown that, in vitro, sHLAs can modulate T-cell reactivity and
      induce cell-activated apoptosis, implicating sHLAs in the induction and
      maintenance of peripheral tolerance. Therefore, sHLAs have the therapeutic
      potential to induce tolerance to transplants.

PMID- 9575495
TI  - Hypoxia and the regulation of gene expression.
AB  - The optimal delivery of oxygen to tissues is essential both to ensure adequate
      energy provision and to avoid the toxic effects of higher oxygen concentrations.
      For this to occur, organisms must be able to sense oxygen and respond to changes
      in oxygen tension by altering gene expression. The analysis of the regulation of
      erythropoiesis has provided important insights into the mechanisms of oxygen
      regulated gene expression. These mechanisms have a role in the regulation of many
      genes, in many cell types and appear to be of relevance to many common
      pathologies in which disturbances of oxygen supply are central.

PMID- 9575496
TI  - Matrix metalloproteinases and TIMPs: properties and implications for the
      rheumatic diseases.
AB  - The matrix metalloproteinases (MMPs) are a unique family of metalloenzymes,
      which, once activated, can destroy all the components of cartilage. MMPs are
      found in resorbing cartilage, bone, rheumatoid and osteoarthritic synovial fluid,
      and adjacent soft tissues. The active enzymes are all inhibited by tissue
      inhibitors of metalloproteinases (TIMPs). The relative amounts of active MMPs and
      TIMPs are important in determining whether cartilage is broken down in joint
      diseases. Conventional treatments for arthritis do little to affect the
      underlying joint destruction, but new drugs are now available that can
      specifically block active MMPs. These potent inhibitors prevent the destruction
      of cartilage both in vitro and in animal models of arthritis. Future trials in
      patients will test their effectiveness in the prevention of cartilage
      destruction.

PMID- 9575497
TI  - [Re-sternotomy].
AB  - The indications and techniques for an pitfalls to avoid which might result in
      complications after resternotomy are reviewed. The relationship between anterio
      mediastinal structures and the posterior aspect of the sternum (as visualized on
      chest, films, CT, or tomography), and other approach(es) including the pros and
      cons of the contemplated procedure must be assessed carefully. Preparations for
      emergency F-F cardiopulmonary bypass must be completed before resternotomy. The
      Wires of the previous operation are undone, but kept in place as safeguards
      during sternal division using an oscillating (not reciprocating) bone saw. After
      their removal, the pericardium or other mediastinal structures adhering to the
      posterior aspect of the sternum are freed before applying a small sternal
      retractor. The pericardial dissection plane is developed at the cardiophrenic
      angle, advanced cephalad and laterally on the surface of the right ventricle and
      atrium. Cephalad dissection starts with imnominate vein identification down the
      superior vent cave, keeping in mind the location of the right phyenic nerve, and
      toward the anterior aspect of the great vessels. Repairing small ventricular or
      aerial lacerations should not be attempted before releasing the tension by sharp
      dissection of the adhesions surrounding the laceration, and repair of great
      vessel injuries is best done under cardiopulmonary bypass.

PMID- 9575498
TI  - [Myocardial protection for cardiac reoperations in patients with valvular
      disease].
AB  - In cardiac reoperations, the less dissection needed, the less potential blood
      loss from divided epicardial adhesions and the less trauma to the heart. However,
      minimal cardiac dissection may result in inadequate topical cooling. Therefore
      the optimal delivery of cardiac solution has a great influence upon postoperative
      myocardial function in cardiac reoperations. We have examined the effect of the
      modified Buckberg's method compared to that of simple cold blood cardioplegia in
      valvular reoperations. In the cases of redo aortic valve procedures, antegrade
      retrograde delivery of cardioplegic solution was done in the modified Buckberg's
      method. It was superior to simple cold blood cardioplegia in terms of the doses
      of dopamine needed when weaning from cardiopulmonary bypass and the ratio of
      spontaneous beating after aortic declamping. Nevertheless, myocardial protection
      measures for hypertrophied myocardium have not yet been established. In
      particular, reoperations for hypertrophied hearts pose many problems for cardiac
      surgeons. To achieve better cardiac function postoperatively, further
      investigations of hypertrophied myocardium are needed at the cellular or
      molecular level.

PMID- 9575499
TI  - [Reoperation after corrective surgery for tetralogy of Fallot].
AB  - Thirty-six patients (7.6%) underwent reoperation after total correction of
      tetralogy of Fallot in our institution from 1955 to 1997. Eight patients
      underwent a second reoperation in the same follow-up period. The indications for
      surgical repair were recurrent or residual lesions alone (Qp/Qs > or = 2.0, right
      ventricule-pulmonary artery pressure gradient > or = 50 mmHg, tricuspid
      regurgitation: (TR) > or = grade 3, pulmonary regurgitation (PR) > or grade 3),
      or in combination with other lesions. The reoperation consisted of closure of a
      residual VSD in 12 patients (33.3%), relief of right ventricular outflow
      obstruction in 12 (33.3%), tricuspid valve repair or replacement for TR in 11
      (30.6%), and pulmonary valve repair or replacement for PR in 10 (27.8%). The
      indications for second reoperation consisted of mainly residual or recurrent TR
      or infections endocarditis. There was one operative death (2.8%) in the
      reoperation group and one death (12.5%) in the second reoperation group. Five
      patients (14.7%) died during a follow-up period of 1-25 years (mean 11.6 years).
      Twenty-none patients (80.6 %) survived surgery, and 25 (86.2%) are now in NYHA
      class I and 4 in class II. Reoperation and second reoperation are associated with
      a low mortality rate and good long-term results in our surgical experience.

PMID- 9575500
TI  - [Reoperation after repair of complete transposition of the great arteries].
AB  - Atrial switch operation (Mustard operation, Senning operation). Rastelli
      operation, and arterial switch operation (Jatene operation) have been performed
      as definitive methods for the repair of complete transportation of the great
      arteries (TGA). Obstruction of the superior vena cavae and the pulmonary venous
      tract are common reasons for reoperation after the atrial switch operation.
      Stenosis of the extracardiac conduit is inevitable after the Rastelli operation
      is performed. Reconstruction of the right ventricular outflow tract using
      Danielson's procedures may eliminate the need for reoperation. The REV procedure
      at the time of initial operation may decrease the incidence of reoperation after
      the repair of TGA with a ventricular septal defect and left ventricular outflow
      tract obstruction. Pulmonary stenosis is the most common reason for reoperation
      after the arterial switch operation. Reconstruction of the pulmonary artery using
      pacifico's method or the single pantaloon patch technique with autologous
      pericardium is expected to reduce the occurrence rate of postoperative pulmonary
      stenosis. Postoperative aortic regurgitation is uncommon and is usually mild in
      grade. However, because the pulmonary sinus is shallow and fragile compared with
      the aortic sinus of Valsalva, the durability of neoaortic valves remains to be
      elucidated during long-term follow-up.

PMID- 9575501
TI  - [Reoperation after the Fontan operation in single ventricle and tricuspid
      atresia].
AB  - The outcome of the Fontan-type operation for complex heart disease has been
      significantly improved, and low morbidity and mortality rates are reported.
      However, some problems still occur in late follow-up, including ventricular
      failure, hepatic congestion, supraventricular arrhythmia, cerebrovascular events,
      exercise intolerance, and residual or new cardiac lesions. Reinterventions after
      the Fontan-type operation for complex cardiac defects in 43 patients are
      reviewed. In addition to catheter interventions, the main reasons for reoperation
      were subaortic stenosis, pulmonary artery and vein obstructions, and interatrial
      shunt. Early intervention, particularly for subaortic obstruction, is
      recommended, and the Damus-Kay--Stansel anastomosis appears to be the procedure
      of choice. Reoperation was required in 6 of the 43 patients, with one operative
      death. The total event-free survival rate after 10 years of follow-up was 53%.
      The need for reoperation appears to be reduced after performing the total
      cavopulmonary shunt procedure compared to that after atriopulmonary connection.
      However, late arrhythmia remains a significant problem in this group of patients,
      and further assessment of the results of reintervention for arrhythmia is
      required.

PMID- 9575502
TI  - [Reoperation for pediatric valvular diseases].
AB  - Grown-up children (GUCH) are one of the major concerns in the field of cardiac
      surgery in children with valvular diseases. In particular, an artificial valve of
      adequate size is sometimes difficult to insert without annular enlargement. In
      cases with complex anomalies such as an univentricular atrioventricular
      connection, the atrioventricular valve should be repaired without the use of an
      artificial valve as often as possible. However, those patients occasionally
      require valve replacement at the initial operation or redo. The specific anatomy
      of the atrioventricular conduction system should be taken into account during
      valve replacement or plasty, particularly during reoperation. In the setting of
      valve replacement in GUCH, the Ross operation or homograft is better than the
      Konno operation or artificial valve replacement.

PMID- 9575503
TI  - [Surgical results and long-term outcome after mitral and/or tricuspid valve re
      replacement].
AB  - Based on the STS/AATS guidelines of 1996, we compared the long-term results after
      mitral (Re-MVR) and/or tricuspid valve re-replacement (Re-TVR) in a total 324
      patients (Re-MVT 299.Re-MVT+TVR 19, and Re-TVR 6 patients) with those after
      initial valve replacement in 763 patients (MVR 741, MVR+TVR 6 and TVR 16
      patients). The actuarial survival (AS), reoperation-free (RF), thromboembolism
      free (TF), and freedom from all valve-related events (EF) rates at the 15th
      postoperative year were 69.3%, 82.4% 86.6%, and 48.9% after Re-MVR and 87.2%,
      92.2%, 83.9%, and 61.4% after initial MVR, respectively. The only significant
      difference between the two MVR groups occurred in the RF proportion. Similarly,
      the incidence of valve-related events after Re-MVR+TVR or Re-TVR was the same as
      that after the initial operation for the respective valve lesions. These long
      term results suggest that valve re-replacement for mitral and/or tricuspid valve
      lesions should be encouraged to the same extent as the initial operation.

PMID- 9575504
TI  - [Reoperation after aortic valve replacement and root reconstruction].
AB  - Between 1984 and 1997, 127 patients in our institution underwent single aortic
      valve replacement (AVR) with the St. Jude Medical valve (group S) and 11 patients
      with a porcine pericardial valve (group T). In the same period, 45 patients
      underwent aortic root reconstruction, among which 39 patients underwent the
      Bentall procedure using Carrel patch coronary reanastomosis (group B). The other
      6 patients were treated with valve-sparing aortic root reconstruction (group V),
      among which the reimplantation method was used in 4 patients and the remodeling
      method in 2. The mean and total follow-up periods of the AVR and aortic root
      reconstruction groups were 6.9 +/- 1.9 year/735 patient-years and 4.9 +/-
      3.9/years/196 patient-years respectively. The actuarial overall survival rates in
      group S and T at 10 years were; 73.8 +/- 7.0% and 85.7 +/- 13.0%, respectively
      The probabilities of freedom from reoperation at 12 years in group S and T were
      97.7 +/- 2.3% and 62.5 +/- 21.3%, respectively. Only one patient in group S
      required reoperation because of valve thrombosis, while 2 patients in group T
      underwent reoperation for prosthetic valve endocarditis. The actuarial overall
      survival rate after aortic root reconstruction at 10 years was 62.6 +/- 9.6%,
      while that of patients with acute aortic dissection and those who did not were
      44.4 +/- 15.7% and 71.7 +/- 11.5%, respectively. The event-free rate at 12 years
      after aortic root reconstruction (group V+B) was 79.1% +/- 20/9%. The reason for
      reoperation in the 2 patients who underwent the Bentall procedure were prosthetic
      valve endocarditis in one and psuedoaneurysm at the right coronary anastomosis in
      the other. The reason for reoperation in one patient who formed a pseudoaneurysm
      was likely due to an oversized conduit hole for the Carrel patch coronary
      anastomosis. One patient in whom the native valve was preserved using the David
      reimplantation procedure required reoperation because of valve degeneration 17
      months after the initial surgery, possibly due to valve rubbing on the vascular
      conduit because of a modified geometry of the Valsalva sinuses. In conclusion,
      because of the low rate of long-term mortality and reoperation, the St. Jude
      Medical valve is an excellent prosthesis for AVR. AVR with a porcine pericardial
      valve yields favorable results in terms of the low long-term mortality although
      the incidence of reoperation remains high. Aortic root reconstruction with the
      Bentall procedure using the Carrel patch method yields acceptable results in
      terms of long-term mortality and low rate of reoperation, although acute aortic
      dissection is an incremental preoperative risk factor. The early results of
      aortic valve-sparing root reconstructive surgery are encouraging, with excellent
      clinical outcomes and patient quality of life. Nevertheless, the indications for
      the procedure must be carefully considered.

PMID- 9575505
TI  - [Coronary reoperation].
AB  - From 1884 to 1997, 24 patients (1.3%) underwent coronary reoperation in a mean of
      10.18 +/- 3.35 ears after the first operation at Juntendo University. The mean
      age of the patients at reoperation was 60.7 +/- 8.0 years. Although 2 patients
      had received a left internal thoracic artery graft at the primary operation, both
      grafts were already occluded. At reoperation, 19 patients received at least one
      internal thoracic artery, and 2 received a gastroepiploic artery graft. The mean
      number of grafts was 1.96 +/- 0.67 at reoperation. One patient underwent
      reoperation combined with pseudoaneurysmectomy at the proximal anastomosis site,
      and one patient reoperation combined with mitral valve replacement. There were 2
      in-hospital deaths. The use of an arterial graft to the LAD is recommended at
      reoperation because of its long-term superiority. Since transmyocardial laser
      revascularization (TMLR) and minimally invasive direct coronary artery bypass
      (MIDCAB) at reoperation have recently been reported, these strategies may be
      considered as useful methods in future.

PMID- 9575506
TI  - [Organ transplantation--approaching the 21st century].
AB  - The first clinical kidney transplantation in a chronic renal failure patient in
      Japan was carried out in March 1964. As of the end of 1997, 12,408
      transplantations had been performed; grafts from living donors were used in
      8,908, while cadaveric grafts were used in 3,500 recipients. As the next step
      after enactment of the law concerning human organ transplants, we must endeavor
      to distribute donor cards and educate people to accept the concept death. At the
      same time, every effort must be made to establish method for induction of graft
      tolerance in the clinical setting.

PMID- 9575507
TI  - [Postgraduate surgical training: what should it be like?].
AB  - Postgraduate training in Japan and board certification by the Japanese Surgical
      Society are reviewed by comparing them with those in other countries to clarify
      the inherent problems and possible solutions. The following are pointed out as
      some of the problems: there is no subjective way to evaluate facilities and
      doctors for certification; the scope of the training curriculum varies among
      institutions, and there is no consistent continuity between education at medical
      schools and postgraduate training. The current system of board certification
      conducted by the medical societies is one major factor in the chaos in
      postgraduate education. The lack of social appreciation and of extra stipends for
      board-certified specialists who expend enormous effort are other problem areas.
      Unless those problems are resolved, the postgraduate surgical training system in
      Japan will remain far from ideal, and it is feared that if the situation persists
      titles will be without substance.

PMID- 9575508
TI  - [Graft-versus-host disease after organ transplantation: donor and host factors].
AB  - Graft-versus-host disease (GVHD) induced by organ transplantation is dependent on
      both the quality and quantity of lymphocytes included in the graft. Changes in
      the host immune function after surgery are also important factors in the
      development of this disease. Based on our experimental data, GVHD after organ
      transplantation is reviewed To test the reactivity of graft lymphocytes in in
      vivo, small bowel, liver pancreas/spleen, and heart/lung transplantations were
      performed using a rat in parent-to-F 1 hybrid combination. All of the lymphoid
      organ transplants induced lethal GVHD, while liver graft did not accelerated the
      disease after the transplantation procedure. Lymphocytes in liver grafts had a
      unique population and showed a low response against alloantigens in vivo.
      Surgical treatments also increased the susceptibility to GVHD, especially the
      ischemic-reperfusion procedure; Endogenous endotoxemia triggered by reperfusion
      promoted the development of lethal GVHD.

PMID- 9575509
TI  - [Asymptomatic pancreatic islet cell tumor (glucagonoma): case report].
AB  - A case of asymptomatic pancreatic islet cell tumor (glucagonoma) is reported. A
      36-year-old woman undergoing a ultrasonic scan was found to have two masses in
      the body and tail of the pancreas measuring 5 cm and 4 cm in diameter,
      respectively. Investigations of serum peptide hormones revealed an elevated
      glucagon level of 27,500 pg/ml (normal < 100 pg/ml), suggesting the possibility
      of an islet cell tumor (glucagonoma). The patient, however, was asymptomatic
      although high levels of glucagon were present. The patient underwent distal
      pancreatectomy to remove the lesions in the body and tail of the pancreas.
      Histological findings revealed islet cell tumors of the pancreas, and immuno
      histochemical staining of the tumor cells demonstrated a positive reaction for
      chromogranin and glucagon.

PMID- 9575510
TI  - [A case of rectal cancer metastatic to the tonsil].
AB  - Metastatic tumors of the tonsils are rarer than primary tumors. Few cases of
      metastatic tonsillar tumor have been reported. A 51-year-old man expectorated a
      portion of a tumor from the left side of the pharynx after an operation for
      cancer metastatic to the lung. Biopsy revealed that the pharyngeal tumor was
      rectal cancer (adenocarcinoma) metastatic to the tonsil. To our knowledge, this
      is the first case of primary rectal cancer metastatic to the tonsil to be
      reported in Japan. The clinical features of metastatic tonsillar tumor are
      discussed.

PMID- 9575511
TI  - PhD graduates and the demands of faculty roles.

PMID- 9575512
TI  - Advanced practice nursing: is the physician's assistant an accident of history or
      a failure to act?

PMID- 9575513
TI  - Building a better system of care for children.

PMID- 9575514
TI  - Managed care: moral conflicts for primary health care nurses.

PMID- 9575515
TI  - Nursing interventions core to specialty practice.

PMID- 9575516
TI  - An alliance for academic home care: integrating research, education, and
      practice.

PMID- 9575517
TI  - Learning along the way: cyberspacial quests.

PMID- 9575520
TI  - ONS position on the care of individuals with HIV infection announced.

PMID- 9575518
TI  - Building community: developing skills for interprofessional health.

PMID- 9575519
TI  - Capitalizing on our currency.

PMID- 9575521
TI  - Proposed national tobacco deal is flawed from public health perspective, new
      report concludes.

PMID- 9575522
TI  - Scientists shed light on anticancer effects of soybeans.

PMID- 9575523
TI  - Congressman honored by Society of Surgical Oncology for support of cancer
      research.

PMID- 9575524
TI  - Contemporary hormonal management of advanced prostate cancer.
AB  - The traditional definition of "advanced" prostate cancer includes only patients
      with widespread osteoblastic or soft-tissue metastases (clinical or pathologic
      stage T any N any M1; or stage D2). Current evidence indicates that this
      definition should be broadened. Because many patients with T3 disease or local
      lymph node metastases progress to distant metastases, the concept of advanced
      prostate cancer should also include stages C and D1 (T3, T4, and any T N1).
      Furthermore, based on pretreatment prostate-specific antigen (PSA) levels, many
      men treated for clinically localized disease will progress rapidly and, depending
      on their age and general health, should be included in the advanced-disease
      category. Also, using prognostic marker modeling with PSA, tumor grade, and other
      factors, recurrences can be predicted even earlier in many cases. This may be
      particularly significant in light of recent clinical data indicating that early
      androgen ablation therapy delays disease progression and improves survival in
      patients with advanced (M0 or M1) disease. The luteinizing hormone-releasing
      hormone (LHRH) agonists have become the preferred method of androgen ablation in
      patients with advanced prostate cancer. Use of an LHRH agonist, alone or combined
      with an antiandrogen, is more acceptable to many patients than orchiectomy and
      lacks the potential cardiotoxicity associated with estrogens. Combined hormonal
      therapy remains controversial but may provide a modest survival benefit,
      especially in men with minimal metastatic disease. Intermittent hormonal therapy
      has great appeal, particularly because of the potentially deleterious effects of
      long-term hormonal therapy; however, its efficacy has yet to be proven.

PMID- 9575525
TI  - Substance abuse issues in cancer patients. Part 1: Prevalence and diagnosis.
AB  - Although rare, drug abuse problems present a complex set of physical and
      psychosocial issues that complicate cancer treatment and pain/ symptom
      management. Most oncologists are not be well versed in either the conceptual or
      practical issues related to addiction. As a result, they often struggle in their
      attempts to effectively treat patients who are or have been substance abusers,
      and they find it difficult to understand issues of addiction in patients with
      pain who have no history of substance abuse. In the first installment of a two
      part series, the authors explore the epidemiology of substance abuse. An
      examination of the distinctions between abuse and dependence leads to definitions
      of these terms appropriate for the oncology setting. Guidelines for assessing
      aberrant drug-taking behavior are also offered. Part 2, which will appear in the
      next issue of ONCOLOGY, will discuss the clinical management of cancer patients
      with a history of substance abuse.

PMID- 9575526
TI  - Clinical trails referral resource. Metastatic breast cancer.

PMID- 9575527
TI  - Chemotherapy for brain tumors.
AB  - Traditionally, cytotoxic drugs have played a limited role in the treatment of
      brain tumors, but important advances in chemotherapy have occurred during the
      past decade. Certain central nervous system (CNS) malignancies are remarkably
      chemosensitive. These include primary CNS lymphoma, medulloblastoma,
      oligodendroglioma, and intracranial germ-cell tumors. This review focuses on
      advances in the chemotherapy of these chemosensitive tumors and also discusses
      the potential use of chemotherapeutic agents, both cytotoxic and cytostatic, in
      other brain tumors, such as glioblastomas and anaplastic astrocytomas. In
      addition, a brief description of future directions that may hold promise,
      including high-dose chemotherapy with stem-cell rescue, blood-brain barrier
      disruption, and regional treatment using controlled-release biodegradable
      polymers, is included.

PMID- 9575528
TI  - Cancer and male factor infertility.
AB  - With the increasing success of multimodality anticancer therapy, most men of
      reproductive age will survive their malignancy. Reproductive function is a
      principal concern of these men. Health-care providers are shifting the focus of
      oncologic care toward improving the quality of life in cancer patients,
      particularly with regard to fertility. For unknown reasons, fertility and sexual
      function are adversely affected in men with germ cell tumors and Hodgkin's
      disease prior to the initiation of therapy. Despite these pretreatment
      abnormalities, fertility potential remains good. Cancer therapy utilizing
      physical and chemical treatment methods can temporarily or permanently damage
      spermatogonia, resulting in azoospermia and infertility. Recovery of
      spermatogenesis can take up to 10 years after therapy. Alternative treatment
      regimens can preserve reproductive function while maintaining high therapeutic
      efficacy. Surgical treatment should be directed toward maintaining the
      neurovascular mechanisms responsible for seminal emission and ejaculation. With
      new developments in assisted reproductive techniques, even cancer patients with
      severe oligoasthenospermia can father children. These techniques have not been
      found to increase the incidence of major or minor birth defects.

PMID- 9575529
TI  - Management of pain in special populations of cancer patients.

PMID- 9575530
TI  - Roles of advanced practice nurses in oncology.
AB  - Managed care is a process of health-care management that integrates financing,
      cost-containment strategies, and business principles with the delivery of health
      care. Managed care's rapid transformation of specialty practices, such as
      oncology, is redirecting classic nursing functions toward market initiatives that
      value the design of care/case management systems and the implementation of
      multidisciplinary "patient-centered" care models. As health-care systems continue
      to evolve, advanced practice nurses (APNs) are redefining their roles and
      enhancing their skills to meet the demands of the marketplace. Advanced practice
      nurses are defined as registered nurses who have met advanced educational and
      practice requirements and are prepared at the graduate level. This paper will
      identify the four established APN roles: nurse practitioner (NP), nurse
      anesthetist, nurse midwife, and clinical nurse specialist (CNS), as well as
      highlight the nurse practitioner and clinical nurse specialist as the leadership
      APN roles within oncology practice. The adaption to managed care has identified
      new functions and created opportunities for these APN specialties that are being
      viewed both competitively by other oncology health-care providers and creatively
      by managed-care organizations. The integration of these emerging roles within the
      new advanced nursing market and their contributions to oncology care are also
      discussed.

PMID- 9575531
TI  - Measurement of visual performance.

PMID- 9575532
TI  - Incidence of corneal ulceration in south India.

PMID- 9575533
TI  - Etiology of pediatric perforating eye injuries in southern Turkey.
AB  - In the present study, the records of 242 children, aged 1-14 years, admitted with
      perforating ocular injury were reviewed retrospectively over a 5-year period.
      There were 175 boys and 67 girls in the study group. The patients were divided
      into 3 groups according to their ages. Perforating injuries occurred most
      frequently in the street in all groups. The second most common place of the
      injury was at home in the 1-9 year-olds and in the fields in the 10-14 year-olds.
      The cause of the perforation was a metallic substance in 32.6%, wood in 15.3%,
      stone in 12.0%, glass in 12.3%, pellets in 12%, and injection needles in 8.3%.
      Most of the perforations occurred during unsupervised play, while all
      perforations with glass occurred during traffic accidents. Surgery was performed
      in 234 patients, while 8 patients in whom spontaneous closure had already
      occurred during admission received only medical treatment. In 28.9% the visual
      acuity was undetermined, in 25.7% the visual acuity was 0.1 or more, in 22.7% the
      visual acuity was between 0.06 and light perception, and in 22.7% there was no
      light perception on final evaluation. It is emphasized that educative and
      legislative measures such as informing the parents, teachers and children about
      the causative factors and potential hazards of perforating ocular injuries and
      restricting the availability of dangerous items to children, should be taken into
      consideration in order to prevent perforating ocular injuries in children.

PMID- 9575534
TI  - Visual function among corneal disease patients waiting for penetrating
      keratoplasty in British Columbia.
AB  - PURPOSE: We sought to test the applicability of a well-documented visual function
      assessment (VF-14) in corneal disease patients wait-listed for penetrating
      keratoplasty to determine if it would be a valuable addition to a priority
      scheme. METHODS: A systematic random sample of patients wait-listed for
      penetrating keratoplasty in British Columbia was selected and administered the VF
      14. RESULTS: The mean VF-14 score was 67.2; it was correlated with best corrected
      vision. Immigrants had lower VF-14 scores and they considered fewer of the
      questions applicable to them. There was a correlation between the number of
      questions considered applicable and the VF-14 score. CONCLUSIONS: As currently
      constituted the VF-14 is probably not a useful tool in a multi-cultural
      population in North America. We propose revisions to the visual function
      assessment and suggest its inclusion in a priority scheme for penetrating
      keratoplasty that also includes pain and other clinical indices.

PMID- 9575535
TI  - A new approach to visual acuity screening for pre-school children.
AB  - The Melbourne Initial Screening Test (MIST) is a vision screening technique which
      combines the features of an established procedure, the five-letter Sheridan
      Gardiner Single (SGS) test, with a pass/fail method of assessment. It is a simple
      screening test for children aged 3.5-4.5 years, which is designed to be easy to
      use. This paper reports on the preliminary results of a comparison of threshold
      acuity using the 5-letter single-optotype Sheridan Gardiner (SG) test and the
      MIST results obtained by orthoptists, and a comparison of MIST results obtained
      by orthoptists and child health nurses. The orthoptists tested 225 children and
      the nurses tested 868 children. The MIST results obtained by the orthoptists were
      similar to the SGS in that there was agreement between the test results in 202
      (94%) cases. The MIST has a similar rate of subject compliance (95%) as the SGS
      test (96%). The rate of compliance for orthoptists' and nurses' use of the MIST
      was similar, with 97% of children being compliant for the nurses and 96% for the
      orthoptists. The results suggest that the MIST, using a pass/fail method of
      assessing visual acuity compared to an assessment of threshold visual acuity, may
      be useful as part of pre-school vision screening since it is easier than the
      traditional testing of threshold visual acuity and gives similar results to the
      SG single-optotype test.

PMID- 9575536
TI  - Annual predictions of adverse outcomes after glaucoma surgery in the United
      States.
AB  - PURPOSE: To predict the number of adverse outcomes or additional ocular surgeries
      after glaucoma surgery in each year from 1990 to 1994 with ordinary and
      hierarchical logistic regression models developed with 1989 Medicare data.
      METHODS: We obtained data on all intraocular and laser glaucoma surgery claims
      (for example, laser trabeculoplasty, full-thickness and partial-thickness
      procedures, and cycloablation) to the Health Care Finance Administration (HCFA)
      in 1989 and developed an ordinary (non-hierarchical) logistic regression model
      and two hierarchical logistic regression models. The two hierarchical models
      smoothed state-level effects to different degrees in an effort to improve the
      precision of model predictions. RESULTS: The hierarchical logistic regression
      models predicted the number of adverse outcomes or additional ocular surgeries,
      including repeat glaucoma surgery, from 1990 to 1994 significantly better than
      the ordinary model. None of the models predicted the downward trend in adverse
      outcomes in 1990 and 1992, although all three models were able to predict the
      increase in adverse outcomes in 1991 and the downward trend in adverse outcomes
      in 1993 and 1994. CONCLUSION: Although systematic changes over time in physician
      practice or billing patterns affected the ability of both ordinary and
      hierarchical regression models to predict the number of adverse outcomes in 1990
      and 1992, hierarchical logistic regression provides a useful framework for
      analyzing adverse event rates when the model contains many covariates with
      imprecisely estimated coefficients. The greater accuracy of predicted adverse
      event rates from ophthalmic surgeries obtained with hierarchical logistic
      regression will be useful for future planning and budgeting purposes.

PMID- 9575537
TI  - Standardized measurement of visual acuity.
AB  - The authors reviewed the main aspects of visual acuity evaluation such as the
      characteristics of the test devices, the notation employed in recording the
      visual acuity level and the procedures for V.A. assessment, in both distance and
      near tests. In addition, new ten-letter charts, that tend to follow strictly the
      standardization guideline suggested by NAS-NRC, are described.

PMID- 9575538
TI  - One-parent families and their dependent children in Great Britain.
AB  - This article analyses a number of aspects of lone parenthood. First, it updates
      the estimated national numbers of one-parent families and dependent children
      living in them. The article then considers the composition of lone parents by
      their marital status and examines the family sizes of lone parent families and
      couple families, as well as contrasting the different age profiles of the
      different kinds of lone parent. Specially commissioned survey data on the marital
      and cohabitational histories of lone mothers, married mothers and cohabiting
      mothers are analysed to give a picture of their differing patterns of past
      partnerships. The article also investigates the people present in lone parent
      households in terms of their relationship to the lone parent.

PMID- 9575539
TI  - Mortality of migrants from outside England and Wales by marital status.
AB  - It is well known that men and women who are married have lower mortality rates
      than those who are not. It is also known that some migrants from abroad have
      higher mortality rates than people in England and Wales and that they have
      different patterns of family formation and dissolution. In this article the
      authors investigate the patterns of mortality by country of birth, marital status
      and cause of death to see if the overall differences in mortality among migrants
      can be explained by their different marital patterns.

PMID- 9575540
TI  - Differences in urban and rural Britain.
AB  - Almost 90 per cent of people in Britain live in urban areas and just over half
      the population are resident in 66 urban areas with populations of 100,000 or
      more. These and a wide range of key results from the 1991 Census have been
      published for all urban areas in Great Britain, updating information that was
      prepared for the first time after the 1981 Census. This article summarises the
      socio-demographic characteristics and distributions of urban and rural
      populations in Great Britain and describes how the distribution of urban
      population has changed in the decade 1981-91.

PMID- 9575541
TI  - Research implications of improvements in access to the ONS Longitudinal Study.
AB  - In this article we outline significant changes in the way the ONS Longitudinal
      Study data are stored, accessed and analysed. The data were held previously on
      mainframe computers. Recent technological changes have made it possible to
      introduce PC-based systems without compromising confidentiality. The advantages
      of this new computing environment are illustrated with recent findings on
      geographic inequalities in health.

PMID- 9575542
TI  - 1996-based national population projections for the United Kingdom and constituent
      countries.
AB  - The 1996-based national population projections, carried out by the Government
      Actuary in consultation with the Registrars General, show the population of the
      United Kingdom rising from 58.8 million in 1996 to over 62 million by 2021. The
      population will become gradually older with the mean age expected to rise from
      38.4 years in 1996 to nearly 42 years by 2021. The number of children aged under
      16 is projected to fall by 1.0 million (9 per cent) by 2021, while the number
      aged 65 and over is projected to increase by 2.7 million (29 per cent). Longer
      term projections suggest the population will peak around 2031 and then gradually
      start to fall.

PMID- 9575543
TI  - Enzymes of lipid A biosynthesis: targets for the design of new antibiotics.

PMID- 9575544
TI  - Biosynthesis of Escherichia coli O9 polysaccharide and its evolution.

PMID- 9575545
TI  - Core structures of enterobacterial lipopolysaccharides.

PMID- 9575546
TI  - Unique structural and biological features of Helicobacter pylori
      lipopolysaccharides.

PMID- 9575547
TI  - What we know and don't know about the chemical and physical structure of
      lipopolysaccharide in relation to biological activity.

PMID- 9575548
TI  - Roles for LBP and soluble CD14 in cellular uptake of LPS.
AB  - Roles for LBP and CD14 in the LPS dependent activation of a wide variety of cells
      have been established. In the work described here, we describe roles for these
      proteins in the binding and uptake of LPS by cells which express membrane CD14
      and those which do not. Surprisingly, cell activation and LPS uptake appear to be
      independent phenomena with different protein requirements.

PMID- 9575549
TI  - Structure-function analysis of soluble and membrane-bound CD14.

PMID- 9575550
TI  - Roles of CD14 in LPS signaling and scavenging: analysis of CD14-transgenic and
      non-transgenic mice and rats in response to LPS.

PMID- 9575551
TI  - The role of scavenger receptors in LPS-induced macrophage activation.

PMID- 9575552
TI  - The CD11/CD18 integrins: characterization of three novel LPS signaling receptors.

PMID- 9575553
TI  - The role of tyrosine kinases and map kinases in LPS-induced signaling.

PMID- 9575554
TI  - CD14 dependent and independent signaling pathways in murine macrophages from
      normal and CD14 "knockout" (CD14KO) mice stimulated with LPS or taxol.

PMID- 9575555
TI  - ADP-ribosylation: role in LPS-induced phosphorylation of two cytosolic proteins
      (p36/38) in monocytes.
AB  - Human monocytes respond to LPS by releasing proinflammatory cytokines such as TNF
      alpha, IL-1 and IL-6. Here we show that inhibitors of ADP-ribosylation namely
      nicotinamide and meta-iodobenzylguanidine prevent production of TNF-alpha and IL
      6 at the protein and mRNA level. The inhibitors also influence the LPS-induced
      phosphorylation pattern of cytosolic proteins. They consistently lead to changes
      of the phosphorylation state of two proteins with an apparent molecular mass of
      36 kDa and 38 kDa. The changes are both time and dose dependent. The data suggest
      that the conditions leading to altered phosphorylation of p36/38 may correlate
      with conditions initiating and regulating TNF-alpha and IL-6 production.

PMID- 9575556
TI  - CD14 dependent mechanisms of cell activation.

PMID- 9575558
TI  - Detoxification of lipopolysaccharide by lysozyme.

PMID- 9575557
TI  - Cytokine regulation of inducible nitric oxide synthase in vascular smooth muscle
      cells.
AB  - NO is an important mediator in sepsis. It has been unequivocally established that
      it is the major determinant in the vasodilatation and consequent hypotension in
      experimental animals following the administration of LPS. It is cytotoxic,
      particularly in combination with superoxide anions, and exerts negative inotropic
      and chronotropic effects on the heart. The exact role that these functions play
      in sepsis, however, remain unclear. Similarly, its immunomodulatory and cerebral
      effects, although potentially important, remain of uncertain significance in
      sepsis. Regulation of such a pivotal molecule is clearly extremely important: the
      data described here show that not only is this regulation extremely complex, but
      it appears to vary in different cell types. The implication of this finding for
      future clinical work is clear. NO production is not all bad: in some
      circumstances, it may be desirable to differentially regulate iNOS activity such
      that production is restricted in some cell types but not in others. The work
      described here begins to offer the possibility of identifying new molecular
      targets which allow this kind of differential regulation.

PMID- 9575559
TI  - Role of hepatocytes in the clearance of lipopolysaccharide and its clinical
      significance.

PMID- 9575560
TI  - Antibiotic-mediated release of endotoxin and the pathogenesis of gram-negative
      sepsis.
AB  - Since the earliest days of antibiotic chemotherapy to treat infection with Gram
      negative microbes, investigators have recognized that such treatments may result
      in the release of microbial constituents that might, in turn, exacerbate the
      pathophysiological manifestations of disease. Both in vitro studies and in vivo
      animal experiments have over the years provided evidence in support of this
      concept; however, the actual clinical importance of this phenomenon to patients
      with Gram-negative sepsis is unclear. Recently published reports from a number of
      laboratories have shown that cell wall-active antibiotics that differ in their
      fundamental mechanisms of action in disrupting microbial growth (via selective
      interactions with various penicillin binding proteins) also differ in their
      relative ability to induce the release of biologically active endotoxin both in
      vitro and in vivo. Further, quantitative differences in total endotoxin release
      correlate well with antibiotic-initiated morphological changes in the microbe. Of
      potential significance is the finding that these differences are also reflected
      in differential production of cytokines from endotoxin-stimulated mononuclear
      phagocytes and other host target cells, including 11-6 and TNF. Since these
      immunologic hormones have been strongly implicated as contributing factors to the
      pathogenesis of Gram-negative sepsis, interest in the potential use of this
      chemotherapeutic approach as a means of controlling the host immunopathologic
      response has increased. Carefully controlled clinical trials in which different
      antibiotic treatments are correlated with production of cytokines will be of
      significant potential value in evaluating the actual significance of this
      phenomenon in the Gram-negative septic patient.

PMID- 9575561
TI  - Molecular mechanisms responsible for endotoxin tolerance.
AB  - Bacterial lipopolysaccharide endotoxin (LPS) is a potent activator of a number of
      inflammatory genes, including interleukin-1 (IL-1). IL-1 and other cytokines such
      as tumor necrosis factor alpha (TNF alpha) are essential mediators in inducing
      severe sepsis syndromes (SS). Major cellular targets of LPS are blood or tissue
      leukocytes, such as macrophages and neutrophils. These cells can respond and
      adapt to LPS, the latter phenomenon is known as LPS tolerance. In animals, LPS
      tolerance is a highly effective mechanism of protection against the lethal
      syndrome of severe sepsis. Two models are used to investigate the molecular basis
      of LPS tolerance. The first model employs blood leukocytes isolated from patients
      with SS. The second model employs the promonocytic cell line, THP-1 in vitro. In
      the SS model, LPS tolerance of involves repression at the level of IL-1 beta
      mRNA. Suppression of IL-1 beta mRNA is under the control of a labile repressor
      protein. In contrast to suppression of IL-1 beta, mRNA is under the control of a
      labile repressor protein. In contrast to suppression of IL-1 beta, there is
      increased expression of the Type 2 IL-1 receptor mRNA and protein in leukocytes
      from patients with SS. The THP-1 model of LPS tolerance also involves repression
      of LPS induction of IL-1 beta gene expression. The repression of THP-1 cell IL-1
      beta expression is at the level of transcription, and like the SS model is under
      the control of a labile protein. LPS tolerance in both models is stimulus
      specific. We further find that transcription factors such as NF kappa B and AP-1
      may participate in regulating LPS tolerance.

PMID- 9575562
TI  - Endotoxin tolerance alters macrophage membrane regulatory G proteins.
AB  - Administration of sublethal doses of endotoxin (LPS) or tumor necrosis factor
      alpha (TNF alpha) renders rats tolerant to supralethal doses of LPS. Peritoneal
      macrophages from tolerant rats are refractory to LPS induced arachidonic acid
      (AA) metabolism and cytokine production in vivo, and exhibit reduced membrane
      GTPase activity and GTP gamma S binding. Since LPS stimulated AA metabolism is
      mediated by Gi alpha proteins, we sought to determine whether Gi alpha and/or
      other G proteins are reduced in LPS tolerance. Rats were rendered tolerant by two
      daily sublethal doses of Salmonella enteritidis LPS, 100 micrograms/kg and 500
      micrograms/kg administered intraperitoneally. Animals were allowed to rest for 72
      hours. Alternatively, tolerance to LPS was induced by sublethal administration of
      human recombinant TNF alpha (10 micrograms/kg) intraperitoneally 24 hrs before
      the experiments. Macrophage membrane G protein content was determined by
      immunoblot analysis with specific antisera to Gi1,2 alpha, Gi3 alpha, Gs alpha
      and the G protein beta subunits (G beta). Membrane G proteins were differentially
      decreased in tolerant macrophages. In macrophages from rats rendered tolerant by
      sublethal doses of LPS, Gi3 alpha was reduced the most to 48 +/- 8% of control (n
      = 3, P < 0.05) and this reduction was significant compared to those of other G
      proteins. Gi1,2 alpha and G beta were reduced to 73 +/- 5% (n = 3, P < 0.05) and
      65 +/- 4% (n = 3, P < 0.05) of control respectively. Gs alpha(L) and Gs alpha(H)
      were also reduced to 61 +/- 5% (n = 3, P < 0.05) and 68 +/- 3% (n = 3, P < 0.05)
      of control, respectively. In contrast, only Gi3 alpha was reduced in macrophage
      membranes from rats pretreated with TNF alpha. Gi3 alpha was reduced to 57 +/-
      11% of control (n = 4, P < 0.05) whereas Gi1,2 alpha and G beta were not
      significantly affected. These results demonstrate selective changes in tolerant
      macrophage membrane G proteins and suggest a potential role for Gi3 alpha in
      mediating LPS tolerance. The molecular mechanisms underlying these changes and
      their significance in LPS tolerance merit further investigation.

PMID- 9575563
TI  - Lipopolysaccharide (LPS) antibodies regulate cellular uptake of LPS and LPS
      induced proinflammatory responses.

PMID- 9575564
TI  - Apoptotic cell death in response to LPS.

PMID- 9575565
TI  - Stimulation of human T lymphocytes by lipopolysaccaride (LPS) in the presence of
      autologous and heterologous monocytes.

PMID- 9575566
TI  - Role of CD14 in infection: studies in CD14-deficient mice.

PMID- 9575567
TI  - Reconciling the concepts of endotoxin sensitization and tolerance.

PMID- 9575568
TI  - Production of nontoxic lipid A by chemical modification and its antagonistic
      effect on LPS activity.

PMID- 9575569
TI  - The protective effect of prostaglandin E1 on endotoxin-induced hepatocyte injury.

PMID- 9575570
TI  - Natural and synthetic LPS and lipid a analogs or partial structures that
      antagonize or induce tolerance to LPS.

PMID- 9575571
TI  - The molecular basis for therapeutic concepts utilizing CD14.
AB  - The CD14 molecule is a key receptor on myeloid lineage cells involved in the
      recognition of lipopolysaccharide (LPS) and Gram-negative bacteria. The
      application of its soluble form, sCD14, has been shown to protect mice from
      lethality in LPS-induced shock. Therefore the protein or its derivatives may be
      considered as a possible therapeutic alternative for the treatment of patients
      suffering from Gram-negative septic shock. In this study we performed an alanine
      scan of amino acids 1 to 152 of human CD14. Twenty-three substitution mutants
      were generated and stably transfected into CHO-cells. In each mutant five amino
      acids were substituted by alanine. We analyzed (a) whether mutant proteins
      expressed on the surface of transfectants were recognized by a panel of anti-CD14
      monoclonal antibodies (mAb's), (b) the ability of mCD14-mutants to bind LPS and
      E. coli in a serum- or LBP-dependent manner, and (c) the capacity of soluble
      mutants to mediate the LPS-induced IL 6 release of U 373 astrocytoma cells.
      Twenty-one CD14-mutants were expressed on the surface of transfectants and 18
      were present as soluble forms in the culture supernatants. We demonstrated that
      only CD14(39-41,43-44)A completely lacked the ability to bind LPS and E. coli. In
      addition, a combined mutant CD14(9-13/57,59,61-63)A had very limited capacity to
      interact with LPS indicating that the LPS-binding site of human CD14 is a
      conformational epitope. Analysis of LPS-induced activation of CD14-negative U 373
      cells revealed that the regions 9-13 and 91-101 are most important for sCD14
      mediated signalling.

PMID- 9575572
TI  - Natural and synthetic polypeptides that recognize the conserved lipid a binding
      site of lipopolysaccharides.

PMID- 9575573
TI  - Prevention of endotoxin shock through targeting leukocyte adhesion molecules.

PMID- 9575574
TI  - Suppression of TNF and other proinflammatory cytokines by the tetravalent
      guanylhydrazone CNI-1493.

PMID- 9575575
TI  - Interaction of lipopolysaccharide with a mammalian lyso-phosphatidate
      acyltransferase (LPAAT) transfected into E. coli, and effect of lisofylline on
      LPAAT transfected into mammalian cells.
AB  - 1. Lipid A and LPS stimulate LPAAT activity (and hence unsaturated PA formation)
      in RMC membranes and whole cells. 2. This correlates with cell phenotypic and
      membrane changes associated with small G proteins. 3. Unsaturated PA and Lipid A
      have similar effects on cells when given exogenously. 4. Human LPAAT-alpha and 
      beta isoforms were cloned and transfected into E. coli, demonstrating the ability
      to restore PA synthesis and reduce lyso-PA accumulation in plsC strains (LPAAT
      deficient mutants), as well as restoring growth at high temperatures. 5. LPAAT
      transfection into E. coli plsC (JC201) strains results in an increase in LPS
      content, suggesting stimulation of LPS synthesis. 6. LPAAT transfection into
      human A549 lung epithelial carcinoma and endothelial ECV304 cells results in
      increased cytokine mRNA transcription at baseline, and a significant increase in
      stimulated cytokine mRNA transcription. In addition, LPAAT transfection also
      results in increased cytokine release in response to IL-1 beta. 7. LSF, which
      reduces rodent deaths in sepsis models, reduces unsaturated acyl incorporation
      into PA in monoblastic cell lines, and reduces serum FFA increase in human
      sepsis, also reduces unsaturated acyl incorporation into PA in ECV304 cells.
      LPAAT-alpha transfection increases linolenate incorporation into PA at the
      expense of linoleate incorporation, which is reversed by LSF. LPAAT-beta
      increases both linoleate and linolenate incorporation into PA, which is also
      reduced by LSF. We conclude that LPAAT and PA remodeling may play a role in
      diffuse renal toxicity in sepsis due to induction of cellular phenotype changes
      associated with PA induction by Lipid A and/or LPS. Two human isoforms of LPAAT
      have been cloned, and apparently address C18 unsaturated acyl chains somewhat
      selectively. LSF causes functional reduction in LPAAT activity in transfected
      systems. This does not yet imply a direct effect of LSF on LPAAT. LPAAT and LPS
      may interact in the membrane in a not-yet-understood manner.

PMID- 9575576
TI  - Role of nitric oxide and reactive oxygen species in endotoxin shock.

PMID- 9575577
TI  - The role of interleukin 6 in endotoxin-induced inflammatory responses.

PMID- 9575578
TI  - The pathogenic role of LBP in gram-negative sepsis and septic shock.

PMID- 9575579
TI  - [Lung diseases in the smoker].

PMID- 9575580
TI  - [Nitric-oxidergic mechanisms in the regulation of the bronchi and their
      significance in the pathogenesis of bronchial asthma].
AB  - AIM: Assessment of NO-synthase (NOS) activity in bronchial asthma (BA) basing on
      cytochemical identification and quantitation of NADPN-diaphorase. MATERIALS AND
      METHODS: Operative samples from 12 BA patients and biopsies from 8 patients free
      of bronchial inflammation or obstruction. Experimental data on control and BA rat
      males injected either with NOS agonist acetyl choline (AC) or beta-2-agonist
      fenoterol (F). RESULTS: A direct relationship was found between BA severity and
      activity of NADPN-diaphorase resultant from activation of inducible NOS (iNOS)
      mediating constrictive effect via different cellular and humoral mechanisms. AC
      treatment caused bronchial relaxation and severe constriction in control and BA
      rats, respectively, though NADPN-diaphorase activity was enhanced in both groups.
      Introduction of F brought about bronchial relaxation in both groups. However,
      there were some cases of constriction in the bronchi with impaired epithelium and
      high baseline iNOS activity. CONCLUSION: In intact bronchial epithelium,
      administration of cholino- and adrenoreceptors agonists induced bronchial myocyte
      relaxation due to activation of constitutive NOS. In impaired bronchial
      epithelium, AC stimulates iNOS induction provoking severe constriction of small
      bronchi.

PMID- 9575581
TI  - [Risk factors and ways to avert early unfavorable outcomes in bronchial asthma].
AB  - AIM: Study of late outcomes of bronchial asthma (BA) and factors of risk of
      rapidly progressive BA course. MATERIALS AND METHODS: A 10-year retrospective
      trial. Examination of 118 patients with BA aged 17-74 years. RESULTS: A rapid
      progression of BA observed in 17(14%) patients led to an unfavorable outcome
      (death, life-threatening conditions, invalidism) as early as the first year of
      the observation. Relevant factors of risk were active eosinophil endobronchitis
      found at fibrobronchoscopy, concomitant active nonspecific infection in the
      bronchi, unjustified use of oral corticosteroids when inhalation steroids were
      possible, family problems. CONCLUSION: Active secondary prophylaxis is necessary
      in patients at high risk of rapidly progressive BA.

PMID- 9575582
TI  - [A complex evaluation of the efficacy of aldecin in treating bronchial asthma
      patients].
AB  - AIM: Study of efficiency of inhalation glucocorticosteroid Aldecine. MATERIALS
      AND METHODS: A 4-week trial of 30 patients with bronchial asthma. Treatment
      results were evaluated by clinical symptoms, demand of inhalation
      sympathomimetics, external respiration, viscosity and elasticity of bronchial
      secretion, concentrations of hydrocortisone and thyroid hormones. RESULTS:
      Aldecine produced a good clinical effect, improved external respiration, allowed
      to reduce doses of inhalation beta-adrenomimetics. No deterioration of either
      bronchial secretion rheology or inhibition of adrenal and thyroid function was
      seen. Candidiasis was clinically negligible. CONCLUSION: Aldecine proved highly
      effective and tolerable in patients with bronchial asthma.

PMID- 9575583
TI  - [The inhalational glucocorticosteroid Inhacort in the treatment of bronchial
      asthma: the efficacy of long-term therapy].
AB  - AIM: The study of efficacy and safety of ingacort in severe and moderate asthma.
      MATERIALS AND METHODS: Clinical response to ingacort, frequency of its
      recurrences, hospitalizations, duration of hospital stay were assessed on the
      treatment month 12, 24 and 36 in 58, 30 and 11 patients with bronchial asthma
      (BA), respectively. RESULTS: 12 months of ingacort treatment promoted a decline
      in BA symptoms: day and night episodes became less frequent, requirement of beta
      2-agonists decreased, bronchial obstruction regressed. Doses of systemic steroids
      were reduced twice or discontinued. Asthmatic statuses occurred 10 times less
      frequently. This effect persisted throughout the following 2 years. Side effects
      were registered within the first year of the treatment and emerged after local
      use of the drug. CONCLUSION: Long-term administration of ingacort in bronchial
      asthma is safe and effective.

PMID- 9575584
TI  - [The effect of salben on the rheological properties of the bronchial secretion].
AB  - AIM: Assessment of the effect of a new Russian selective sympathomimetic salben
      (powder for inhalations) on bronchial secretion viscosity and adhesion. MATERIALS
      AND METHODS: Salben or placebo (sodium bensoate) were given to 82 and 30 patients
      (control) with bronchial asthma, respectively. The response was assessed by
      clinical, laboratory and instrumental findings. RESULTS: A statistically
      significant (p < 0.05) reduction of the viscosity and adhesion (by 15 and 20%,
      respectively) was noted in the salben group which also demonstrated improved
      external respiration. CONCLUSION: Salben induced positive effect on bronchial
      secretion viscosity and adhesion.

PMID- 9575585
TI  - [The adaptive reactions of the cardiorespiratory system in chronic bronchitis and
      its premorbid forms].
AB  - AIM: Investigation of pulmonary ventilation, blood flow and cardiodynamics in
      subjects at risk of chronic nonspecific pulmonary disease (CNPD), prebronchitis
      (PB) and chronic bronchitis (CB). MATERIALS AND METHODS: 118 workers exposed to
      toxico-chemical factors underwent zonal rheography. RESULTS: At early stages of
      CB marked disorders of pulmonary ventilation and blood flow in the lungs were
      revealed. These disorders in subjects with threatened CNPD were regional and
      accompanied by a moderate increase in power inputs of the cardiorespiratory
      system. The maintenance of adequate pulmonary exchange in patients with PB
      entailed functional tension of the respiratory and cardiovascular systems that
      contributed to decompensation of adaptive mechanisms and occasionally to
      development of rheographic signs of pneumosclerosis in the lung zones with
      damaged ventilation and low perfusion of the pulmonary vessels. CONCLUSION:
      Overloading and decompensation of respiratory and cardial mechanisms of gas
      exchange regulation in the lungs in response to external damage may lead to
      development of myocardiodystrophy and pneumosclerosis which appear to be the
      "price of adaptation".

PMID- 9575586
TI  - [Lipid peroxidation processes in chronic bronchitis].
AB  - AIM: Comparison of the levels of lipid peroxidation (LPO) products in condensate
      of the exhaled air (CEA) and in the biopsy samples from the inflammation focus.
      MATERIALS AND METHODS: Extraction spectrophotometry was used to measure LPO
      products in CEA and biopsies from 30 males aged 30-60 years suffering from
      chronic bronchitis and 30 healthy controls of the same age. RESULTS: There was
      activation of local accumulation of isopropanol-soluble LPO products in the
      bronchopulmonary system accompanied by lowered content of lipoperoxides and high
      antioxidant activity in CEA. CONCLUSION: Chronic bronchitis is characterized by
      multidirectional shifts in LPO in the inflammation focus and CEA.

PMID- 9575587
TI  - [The clinico-immunological efficacy of the likopid treatment of chronic
      bronchitis patients].
AB  - AIM: Elucidation of likopid effect on clinical and immunological pictures in
      patients with chronic bronchitis (CB). MATERIALS AND METHODS: A trial of 52 CB
      patients in remission and exacerbation. 2 schemes of likopid treatment were used:
      1 mg/day for 10 days (a course dose 10 mg); 10 mg/day for 6 days (a course dose
      60 mg). Clinical and laboratory parameters, systemic immunity (measurement of
      lymphocyte subpopulations, levels of serum IgA, IgM and IgG, functional activity
      of peripheral blood phagocytes). RESULTS: The 10 mg and 60 mg courses of likopid
      produced prolongation of remission to 5-6 months in 66% of CB patients in
      exacerbation and in 80% of patients in remission, respectively. 10 mg of likopid
      in exacerbation and 60 mg in remission promoted normalization of functional
      activity of blood phagocytes. CONCLUSION: Likopid administration for CB in a 10
      mg course dose in exacerbation and 60 mg course in remission prolongs CB
      remission to 5-6 months and promoted normalization of phagocytic functional
      activity.

PMID- 9575588
TI  - [Risk factors and the molecular cellular mechanisms of a protracted course in
      pneumonia].
AB  - AIM: Investigation of risk factors and molecular-cellular. mechanisms of
      development of lingering pneumonia (LP). MATERIALS AND METHODS: Examination
      covered 202 patients with acute pneumonia and 199 patients with LP. RESULTS: LP
      was characterized by deeper suppression of immunity, restructuring of the lipid
      bilayer, changed microviscosity and enzymic activity of red cell membranes as a
      result of infectious-toxic factor, activation of lipid peroxidation, suppression
      of the antioxidant defense. CONCLUSION: The findings contribute to design of more
      detailed principles of pathogenetic therapy and prevention of LP.

PMID- 9575589
TI  - [The cardiological manifestations of the obstructive sleep apnea syndrome.
      Clinical cases].
AB  - Two cases of sick sinus syndrome with asystole in patients with obstructive sleep
      apnea syndrome are reported. Management of such patients using CPAP therapy is
      detailed. The apnea symptoms and somnological history are important in evaluation
      of the condition of patients with sleep cardiac arrhythmia especially in patients
      with day sleepiness, night snore and obesity.

PMID- 9575590
TI  - [The initial experience of using extracorporeal plasmoimmunosorption with protein
      A in the combined treatment of patients with small-cell lung cancer].

PMID- 9575591
TI  - [Chronic nonspecific lung diseases in workers in the gold-mining industry].
AB  - AIM: Assessment of prevalence, specific characteristics of chronic nonspecific
      pulmonary diseases (CNPD) in gold-miners. MATERIALS AND METHODS: The examination
      of a therapist, otorhinolaryngologist, ophthalmologist, total blood count,
      urinalysis, computer spirography, chest fluorography and ECG were included in the
      survey covering 1110 gold miners 18-65 years of age. 78.56% of them were exposed
      to occupational hazards. RESULTS: CNPD were diagnosed in 362 (33.62%) examinees,
      279 (25.14%) demonstrated symptoms of prebronchitis. Most of CNPD patients were
      at the age from 30 to 59 years. The majority of them worked in detrimental
      conditions 10 years and longer. Among CNPD-free subjects were those exposed to
      the risk factors for up to 5 years. Prebronchitis developed in those who worked
      at least 5 years. Such risk factors as occupational hazards, smoking,
      bronchopulmonary lesions in close relatives, frequent acute respiratory
      infections, allergy, abnormalities of the upper respiratory tracts contributed to
      the onset of CNPD. Combination of 3 and more risk factors led to CNPD most often.
      45 patients (20 with prebronchitis and 25 with chronic bronchitis) were treated
      with a positive effect. Rehabilitation measures comprised physiotherapy, massage,
      respiratory exercise, inhalation of anticholinergic and mucolytic drugs.
      CONCLUSION: In gold miners examined CNPD occurred in 32.62%. CNPD occurrence
      correlated with duration of service. 25% of the examinees had prebronchitis which
      arose after 5-6 years of work in detrimental conditions. This is just the time
      for measures to prevent chronic bronchitis.

PMID- 9575592
TI  - [Tumor diseases of the blood system: age, cholesterol level and erythrocyte
      count].
AB  - AIM: Illustration of potentialities of computer technologies in processing data
      from case histories MATERIALS AND METHODS: Routine clinical and laboratory data
      on 263 hemoblastosis patients were processed with the use of the exploring
      system. RESULTS: A paradoxical negative relationship was discovered between blood
      cholesterol and age (R = -0.345, p < 0.00001), and a positive correlation between
      cholesterol and number of red cells (R = 0.379, p < 0.00001). In comparison of
      groups with low and high cholesterol, the latter group showed more favourable
      values of hemoglobin, red cells, other hematological and biochemical parameters.
      It seems that among hemoblastosis patients and healthy subjects there are
      subjects with standard age-related changes of cholesterol and paradoxical changes
      (a negative correlation). The conception about high level of cholesterol as a
      factor stimulating proliferation of normal and affected cells in patients with
      hemoblastoses appears doubtful. At least it is not correct to connect a
      combination hypocholesterolemia + anemia with low pool of dividing cells. On the
      contrary, hypocholesterolemia in hemoblastoses indicates active tumor process
      with consequent anemia. CONCLUSION: Investigation of paradoxical relationships
      between age, cholesterol and red cell count (hemoglobin) will help understand
      general mechanisms of regulation of hemo- and immunogenesis in blood
      malignancies.

PMID- 9575593
TI  - [Leukocyte and thrombocyte glycosaminoglycans in hemophilia A and von
      Willebrand's disease].
AB  - AIM: The study of glycosaminoglycanes (GAG) in leukocytes and platelets of
      patients with hereditary coagulopathy. MATERIALS AND METHODS: GAG concentration,
      composition and fraction identification were made in 25 patients with hemophilia
      A and 10 patients with Willebrand disease. RESULTS: In hemophiliacs, leukocytes
      contained low concentrations of GAG. In those with bleeding and synovitis GAG
      levels were lower than the average, in those with extensive hematomas in the
      absence of locomotor disorders the above levels were close to normal.
      Chondroitinsulphate dominated in GAG composition though it was less polydisperse.
      Heparin sulphate levels were elevated. Platelet GAG characteristics were close to
      normal. In Willebrand disease leukocyte GAG content and composition was similar
      to those in hemophilia A except some differences in electrophoretic properties of
      small GAG components. CONCLUSION: Metabolism and/or release of GAG from blood
      cells may be involved in pathogenesis of hemophilia A and Willebrand disease.

PMID- 9575595
TI  - [The diagnosis and drug therapy of allergic dermatoses].

PMID- 9575594
TI  - [A trial of the use of the low-molecular heparin sulodexide in the therapy of
      diabetic nephropathy].
AB  - AIM: Investigation of sulodexide effects on renal function, hemostasis and lipid
      metabolism in patients with diabetes mellitus. MATERIALS AND METHODS: 20
      diabetics (diabetes mellitus type I and II) received sulodexide (Vessel due F)
      for 3 weeks. This mixture of low molecular heparin and dermatan sylphate was
      injected i.m. once a day for 5 days a week with a 2-day interval. Micro- and
      macro-albuminuria diminished after treatment but further returned to baseline
      levels. The rate of glomerular filtration, blood levels of glucose and
      cholesterol, hemostatic parameters remained unchanged. Blood triglycerides fell.
      CONCLUSION: Sulodexide may be useful in pathogenetic treatment of diabetic
      nephropathy.

PMID- 9575596
TI  - [Current concepts of liposomes and the outlook for their use in pulmonology].

PMID- 9575597
TI  - [The efficacy and unsafeness of using antiasthmatic drug agents].

PMID- 9575599
TI  - Randomized controlled trial of antioxidants in intermittent claudication.
AB  - Epidemiological evidence suggests that antioxidants protect against the
      development of atherosclerosis. To determine the effectiveness of antioxidant
      therapy in patients with lower limb atherosclerosis, a randomized placebo
      controlled trial was performed in 120 men and women with intermittent
      claudication and an ankle/brachial pressure index (ABPI) < or = 0.9. The study
      was analysed on an intention-to-treat basis. After 2 years, there were no
      significant differences between antioxidant and placebo groups in plasma
      cholesterol, lipoproteins, haemostatic or rheological factors. However, after 6
      months, low density lipoprotein cholesterol was significantly lower in those
      taking antioxidant (108.0 mg/dl compared with 120.1 mg/dl, p < 0.05). There were
      no differences in the ABPI or walking distance, although both groups improved
      slightly with time. The incidence of cardiovascular events and death was
      nonsignificantly lower in the antioxidant compared with the placebo group: event
      rates per year were 5.5% (95% CI 2.4-8.6) in the first year and 9.6% (95% CI 6.8
      12.4) in the second year for those on antioxidants; and 7.7% (95% CI 5.1-10.3)
      and 13.3% (95% CI 8.9-17.7) respectively for those on placebo. Significantly
      fewer serious adverse events occurred in the antioxidant than the placebo group:
      21.8% (95% CI 16.2-27.4) compared with 40.0% (95% CI 33.9-46.1). This study
      therefore suggests that although antioxidants may prevent cardiovascular events
      in patients with peripheral atherosclerosis, they do not improve lower limb
      function.

PMID- 9575600
TI  - The relationship between free-living daily physical activity and the severity of
      peripheral arterial occlusive disease.
AB  - The purposes of this study were to assess the magnitude of the reduction in free
      living daily physical activity of claudicants compared with age-matched controls,
      and to examine the relationship between the severity of peripheral arterial
      occlusive disease (PAOD) and free-living daily physical activity. Eighty-five
      PAOD patients with intermittent claudication and 59 non-PAOD subjects with a
      resting ankle/brachial index (ABI) of 0.63 +/- 0.20 and 1.21 +/- 0.08,
      respectively, were monitored for 2 consecutive weekdays with an accelerometer and
      pedometer worn on each hip. The times to onset and to maximal claudication pain
      were also measured in the claudicants during a graded treadmill test to assess
      the functional limitations imposed by PAOD. The PAOD group had a 42% lower energy
      expenditure as measured from the accelerometer (357 +/- 238 kcal/day versus 616
      +/- 363 kcal/day; p < 0.001) and a 45% lower pedometer reading (4737 +/- 2712
      steps/day versus 8672 +/- 4235 steps/day; p < 0.001) than the non-PAOD group.
      Furthermore, the relationship between free-living daily physical activity and ABI
      in PAOD patients was significant for both the accelerometer (r = 0.41; p < 0.001)
      and the pedometer (r = 0.41; p < 0.001). The rate of decline in free-living daily
      activity was 42 kcal/day and 612 steps/day per 0.10 drop in ABI. The correlation
      between free-living daily physical activity and time to maximal claudication pain
      (6:25 +/- 3:30 min:s) in the PAOD group was significant for both the
      accelerometer (r = 0.30; p = 0.05) and the pedometer (r = 0.36; p = 0.03).
      However, the time to onset of claudication pain (3:02 +/- 2:22 min:s) in the PAOD
      group was not related to either the accelerometer (r = -0.02; p = 0.86) or the
      pedometer (r = 0.18; p = 0.28) activity values. In conclusion, free-living daily
      physical activity was 42% to 45% lower in PAOD patients with intermittent
      claudication than in apparently healthy subjects of similar age. Moreover,
      claudicants were progressively more sedentary with an increase in PAOD severity.

PMID- 9575601
TI  - Antiaggregatory effects of picotamide in long-term treatment: a 2-year, double
      blind placebo-controlled trial.
AB  - The ex vivo antiaggregatory activity of picotamide, a dual antithromboxane agent,
      was assessed to find whether it was maintained in long-term treatment. In a
      double-blind, placebo-controlled 2-year study, 50 type 2 diabetic patients (35
      men and 15 women; mean age 66 +/- 5 years) were enrolled and randomly given
      picotamide, 300 mg t.i.d. or the corresponding placebo. Platelet aggregation
      studies were performed at baseline and after 1, 3, 6, 12, 18 and 24 months.
      Compliance to the treatment was assessed by pill count at each visit. Forty-nine
      patients concluded the study. Starting from month 1, compared with placebo,
      picotamide-treated patients showed a significant inhibition of agonist-induced
      (ADP, arachidonic acid and collagen) platelet aggregation (-41%). The
      antiaggregatory effect was maintained throughout the study. At month 24, in the
      picotamide group, platelet aggregation was significantly lower compared with
      placebo (-30%). After 24 months of treatment, 20 out of 23 (86%) picotamide
      treated patients showed a significant inhibition of platelet aggregation, whereas
      the remaining three patients had a normal platelet response. During the study, 12
      patients suffered from thrombotic events of death: nine in the placebo group and
      three in the picotamide group, respectively. It was concluded that picotamide
      maintains its antiaggregatory effect, in long-term treatment, in more than 85% of
      patients.

PMID- 9575602
TI  - The occurrence of Raynaud's phenomenon in a general population: the Framingham
      Study.
AB  - The prevalence and predisposing conditions for primary and secondary Raynaud's
      phenomenon (RP) were examined in The Framingham Study based on 16 years of follow
      up of a cohort of 4182 men and women. The association with atypical chest pain
      and migraine headache was also investigated. Over the 16 years of follow-up there
      were 130 men and 171 women who developed primary RP. The prevalence in women
      (9.6%) was somewhat higher than in men (8.1%) and 81.4% of the RP was primary.
      Secondary RP was equally prevalent in men (18.6%) and women (19.7%). The most
      common causes of secondary RP were beta-blocker use (34.2%), carpal tunnel
      syndrome (10.5%) and rheumatoid arthritis (7.2%). Primary RP cases differed from
      noncases by having lower systolic blood pressure (p < or = 0.001) and diastolic
      blood pressure (p < 0.0001), and more coronary disease (p = 0.009), smoking (p <
      or = 0.01) and higher blood sugars (p < or = 0.009). Atypical chest pain was
      present more often than noted previously in The Framingham Study general
      population survey, and was equally prevalent in primary and secondary RP and in
      the two sexes. Associated migraine was more prevalent in women (14.4%) than men
      (5.0%). Vibrating tool use with associated RP occurred in 14.6%.

PMID- 9575603
TI  - Basal nitric oxide production is not reduced in patients with noninsulin
      dependent diabetes mellitus.
AB  - Vascular disease is the leading cause of morbidity, disability and death in
      patients with noninsulin-dependent diabetes mellitus. Abnormalities in
      endothelium-derived nitric oxide (NO) have been demonstrated to be involved in
      the pathogenesis of vascular disease. By measuring hemodynamic responses to a NO
      synthase agonist or antagonist, previous studies have shown the presence of NO
      deficiency in patients with noninsulin-dependent diabetes mellitus, a method of
      assessing bioactive NO formation. However, direct biochemical evidence that this
      is the case, has not been produced. In vivo NO is metabolized into nitrate, an
      end breakdown product of NO, which can be used as an index of endogenous NO
      formation. To investigate further whether decreased basal synthesis of NO may be
      a major cause of endothelium-mediated vascular dysfunction in patients with
      noninsulin-dependent diabetes mellitus, the plasma nitrite/nitrate levels of 15
      patients were examined and compared with 13 normal controls. The results showed
      that in basal conditions plasma nitrite/nitrate levels were not reduced in
      diabetic patients compared with normal controls (37.3 +/- 14.7 versus 29.4 +/-
      8.6 mumol/l). It was concluded that in noninsulin-dependent diabetes mellitus
      patients, endothelium-derived basal NO formation is not impaired. This study,
      taken with previous observations, suggests that factors other than diminished
      basal NO production, such as reduced bioavailability of NO probably due to the
      augmented production of superoxide anion with subsequently increased inactivation
      of NO, contribute to the high incidence of vascular disease in patients with
      noninsulin-dependent diabetes mellitus.

PMID- 9575604
TI  - Hemostatic/fibrinolytic predictors of allograft coronary artery disease after
      cardiac transplantation.
AB  - Allograft coronary artery disease (CAD) remains the leading cause of morbidity
      and mortality affecting the long-term survival of patients after cardiac
      transplantation. Because there is increasing evidence that imbalances in
      hemostatic and fibrinolytic pathways are associated with graft failure, we
      hypothesized that atherothrombotic risk factors may contribute to allograft CAD.
      This study sought to determine if plasma hemostatic and fibrinolytic parameters
      are associated with the severity of allograft CAD. The extent of allograft CAD
      was investigated by angiography and intravascular ultrasound (IVUS) in 16 cardiac
      transplant recipients. Intimal thickening was quantified using IVUS by measuring
      the intimal index (li = intimal area/[intimal area + luminal area]) in two to
      five segments of the left anterior descending (LAD) coronary artery. The maximal
      li per patient was calculated and index to the time post-transplant (Mxli/Yr).
      Plasma fibrinogen (FGN), tissue-type plasminogen activator (t-PA), plasminogen
      activator inhibitor-1 (PAI-1), lipoprotein(a) (Lp(a)), and net fibrinolytic
      activity of plasma were assayed 6-24 months after transplant as indicators of the
      fibrinolytic system and then correlated with the IVUS measurements. The FGN level
      correlated with the severity of intimal thickening, Mxli/Yr (r2 = 0.41, p =
      0.008), and was inversely correlated with angiographic tertiary vessel filling
      (r2 = 0.25, p = 0.051). In patients with lower plasma fibrinolytic activity
      (lytic zone less than 100 mm2), Mxli/Yr was increased eightfold (0.218 +/- 0.137
      versus 0.025 +/- 0.021, p = 0.001). t-PA (r2 = 0.0004, p = 0.94), PAI-1 (r2 =
      0.008, p = 0.75) and Lp(a) levels (r2 = 0.11, p = 0.21) did not predict Mxli/Yr.
      Thus, we demonstrate that plasma FGN and net fibrinolytic activity correlate with
      the degree of intimal thickening measured by IVUS after cardiac transplantation.
      These data suggest that fibrin deposition may play a role in allograft CAD after
      cardiac transplantation.

PMID- 9575606
TI  - Lymphedema: anatomy, physiology and pathogenesis.
AB  - The authors review the current understanding of lymphatic anatomy and physiology,
      and the pathophysiology of lymphedema. The skin lymphatic system consists of the
      initial lymphatics, which converge into lymphatic precollectors, collectors and
      lymphatic ducts; these in turn convey the lymph to the regional lymph nodes.
      Interstitial fluid and particles enter the initial lymphatics through
      interendothelial openings and by vesicular transport. Lymphatic uptake is
      enhanced by external compression. Lymphatic transport depends greatly on
      contraction of lymphangions, which generate the suction force that promotes
      absorption of interstitial fluid and expels lymph to collecting ducts. In
      lymphedema, various types of congenital and acquired abnormalities of lymphatic
      vessels and lymph nodes have been observed. These often lead to lymphatic
      hypertension, valvular insufficiency and lymphostasis. Accumulation of
      interstitial and lymphatic fluid within the skin and subcutaneous tissue
      stimulates fibroblasts, keratinocytes and adipocytes eventuating in the
      deposition of collagen and glycosaminoglycans within the skin and subcutaneous
      tissue together with skin hypertrophy and destruction of elastic fibers.

PMID- 9575605
TI  - Inherited hypercoagulable states.
AB  - Hypercoagulable states are a group of conditions associated with increased
      predisposition to thromboembolic events. Most of the inherited abnormalities
      recognized to date are associated with venous thromboembolism (VTE) rather than
      arterial thrombosis. The well-recognized inherited hypercoagulable states are the
      deficiencies of antithrombin, protein C and protein S, and the resistance to APC
      (factor V Leiden). These entities represent aberrations in the natural
      anticoagulant systems that exist in plasma. Other causes of inherited
      thrombophilia include abnormalities in the proteins of the fibrinolytic system,
      dysfibrinogenemias, deficiency of heparin cofactor II, abnormal thrombomodulin,
      elevated levels of histidine-rich glycoprotein, and the recently described
      variation in the prothrombin gene. One entity that has become firmly established
      as a predisposing factor for recurrent VTE is hyperhomocysteinemia. About half of
      VTE episodes in patients with inherited thrombophilias occur in relation to
      events that are generally recognized as predisposing states, such as surgery,
      pregnancy (particularly puerperium) and immobilization. In this review, the risks
      of VTE associated with inherited risk factors are discussed, and guidelines for
      the diagnosis and management are presented.

PMID- 9575608
TI  - Images in vascular medicine. Jugular vein thrombosis.

PMID- 9575607
TI  - Primary angioplasty for acute myocardial infarction.
AB  - The use of thrombolytic therapy has been widely accepted for the treatment of
      acute myocardial infarction. Despite improving mortality, thrombolytic therapy
      may be contraindicated in many patients presenting with myocardial infarction and
      is associated with a small, yet significant risk of hemorrhagic sequelae. This
      article outlines the rationale behind reperfusion therapy, the use of
      pharmacological thrombolysis and the role of adjunctive angioplasty. The
      potential advantages of a therapeutic strategy of primary angioplasty, instead of
      thrombolysis, are discussed. These include anatomical definition, risk
      stratification, reduced recurrent ischemia, enhanced coronary perfusion and
      improved coronary patency. The randomized trials in which primary angioplasty and
      thrombolytic therapy were compared are reviewed. We conclude that angioplasty
      results in a reduction of short-term mortality and nonfatal reinfarction and
      therefore advocate the routine use of coronary angioplasty as a primary
      reperfusion strategy for acute myocardial infarction. The potential limitations
      of primary angioplasty in the community hospital setting are discussed. Finally,
      we examine the roles of adjunctive mechanical (e.g. stents) and pharmacological
      (e.g. Abciximab) means of further enhancing outcomes after primary angioplasty.

PMID- 9575609
TI  - [Oxidative modification of cytochrome P450 and other macromolecules during its
      turnover].
AB  - Possible mechanisms of cytochrome P4502B4 modification by H2O2 formed during
      catalytic turnover have been studied. Oxidative self-inactivation of cytochrome
      P4502B4 in monooxygenase system, reconstituted from highly purified membrane
      proteins: cytochrome P4502B4, NADDPH-cytochrome P450 reductase and cytochrome b5
      in the presence of detergent Emulgen 913, involves the heme destruction and
      apoenzyme modification. The cytochrome P450 self-inactivation is accompanied by
      protein aggregation, oxidation of SH-groups and changes of the surface charge.
      H2O2 and non-specific radical reactions may be responsible for the intermolecular
      cross-linking. Oxidative modification of cytochrome P4502B4 may be initial stage
      of the protein decay in the cell.

PMID- 9575610
TI  - [Alzheimer's disease: beta amyloid and lipid metabolism].
AB  - Amyloid deposits found in brains of Alzheimer's disease. Down's syndrome and
      normal aged individuals are composed mainly of aggregated amyloid beta (Ab),
      soluble form which is a normal protein. We previously reported that soluble Ab
      (sAb) in normal human plasma and cerebrospinal fluid is complexed to high density
      lipoprotein (HDL). Consequences of sAb association with the HDL and Ab
      involvement in the lipid turnover are discussed herein.

PMID- 9575611
TI  - [Cathepsins L and B and their endogenous inhibitors in embryonal fibroblasts
      transformed by different genes].
AB  - Expression of cysteine proteinases, cathepsins L and B, and their inhibitors was
      studied out in three model systems of rat embryo fibroblasts, sequentially
      immortalized and transformed by different genes. In Model I rat embryo
      fibroblasts were immortalized with DNA of early region of simian adenovirus SA7
      (clone REF-1) and then transformed by c-Ha-ras oncogene (REF-2EJ; malignant
      transformation). In Model II and III, the immortalized fibroblasts (clone IE5)
      were obtained by transfection with the polyoma virus LT gene and the clone IE5
      used lost this gene; the malignant transformation was achieved by transfection
      with the E7 gene (clone trF8; Model II) and E6/E7 genes ?clone A5E5(pC7-1); Model
      III]? of human papilloma virus types 16 and 18 respectively. In Model I, the
      increase in the total cathepsin L and B activity was correlated with the stages
      of transformation, at the same time, in Models II and III, this activity in
      immortalized IE5 fibroblasts was higher than at transformation stage. The
      activity of cathepsin L in lysates of transformed fibroblasts--REF-2EJ,
      significantly exceeded this activity both in transformed cells trF8 and A5E5(pC7
      1)(6- and 10-fold, respectively). In cell cultures of Models I and II, the
      increases in secreted activity of cathepsins L and B were correlated with the
      stages of fibroblasts transformation, but in cultures of Model III, this activity
      at the stage of malignant transformation was lower than that the stage of
      immortalization. Therefore, the activities of cathepsins L and B were expressed
      to varying degrees at different stages of oncogenic transformation and the
      expression of their activities were dependent on type of transforming gene. It
      was established that changes in proteolytic potential were correlated with
      differences in the transforming phenotype of cell clones. An endogenous
      inhibitor(s) of cysteine proteinases was found in conditioned media of all type
      cell cultures. Expression and inhibitory properties of this inhibitor(s) were
      different at distinct stages of transformation.

PMID- 9575613
TI  - [The hormone-metabolic changes in the diabetic angiopathy].
AB  - Biochemical, morphological and electron-microscopic readings of blood serum,
      liver, aorta and brain vessels, and in crystalline lens were investigated in
      intact and experimental animals during the process of experimental diabetes
      mellitus formation. The experimental diabetes mellitus was induced by L
      adrenaline implementation and atherogenous load. Characteristics of lipid
      metabolism, peroxide lipid oxidation, sorbitol way of glucose metabolism, glucose
      and insulin levels conform to diabetes mellitus. Diabetic lipid metabolism
      impairments were accompanied with changes in microcirculation--a cause of
      diabetes mellitus complications. These data were supported by morphological and
      electron-microscopic readings. The results of the study confirm the hormone
      hypothesis of diabetic complications and stress (high adrenaline level) factors
      of Diabetes Mellitus pathogenesis.

PMID- 9575612
TI  - [The effect of oxidized low density lipoproteins on ADP-induced platelet
      aggregation in plasma].
AB  - The investigation of the effect of oxidized lipoproteins on platelet activity is
      important for the understanding of the plague formation under atherosclerosis. In
      the present work, we examined the influence of low density lipoproteins (LDL) on
      ADP-induced platelet aggregation in the platelet rich plasma. In was demonstrated
      that mixing of plasma and LDL was accompanied by the decrease of ADP-induced
      aggregation parameters as compared to control (mixing with buffer). After 1 h
      incubation, platelet ADP-aggregation in the sample containing oxidized LDL
      (oxLDL) exceeded the ADP-aggregation in the control sample. The dependence of the
      aggregation parameters on the incubation time and on the degree of LDL oxidation
      were obtained. No difference in the cholesterol and phospholipid content was
      observed between cells incubated with buffer, native or oxidized LDL. Therefore,
      the possible oxLDL-induced accumulation of cholesterol in platelet membranes is
      excluded as a reason for the increased cell aggregation.

PMID- 9575614
TI  - [Protein-protein recognition: testing of some hypotheses of binding site's
      structure using Brookhaven data bank].
AB  - Four amino acid's complementarity hypotheses have been checked using the data on
      the structure of 122 protein complexes taken from protein Brookhaven Data Bank.
      No one of hypotheses was conformed at the analysis of the contact region
      structures of the protein complexes examined.

PMID- 9575615
TI  - [The measuring of blood plasma antioxidant activity by the hemoglobin-hydrogen
      peroxide-luminol system].
AB  - The method of valuation of the blood plasma antioxidant activity (AOA) by the
      hemoglobin-hydrogen peroxide-luminol chemiluminescence system has been proposed.
      The method is based on the measuring the induction time of chemiluminescence that
      is directly proportional to the added volume of plasma or concentration of
      standard antioxidant. The ascorbate was taken as a standard. Blood plasma AOA has
      been expressed through the concentration of equivalent ascorbate solution
      (ascorbate equivalent). The influence of hemolysis and storage conditions of
      plasma on its detected AOA was investigated. The change of human blood plasma AOA
      after single administration of 2 g the ascorbate and its dynamics in patients
      with acute pancreatitis was studied.

PMID- 9575616
TI  - [Expression of integrins in human intestinal carcinoma cells differing in
      substrate specificity of apoptosis].
AB  - A cell population, characterized by a capacity to survive in the absence of cell
      attachment to a substrate (anoikis-independent cells), was selected from the
      original anoikis-dependent human gut carcinoma line Caco-2. In cell-adhesion
      assays, anoikis-independent cells demonstrated much lower affinity to fibronectin
      compared to their anoikis-dependent counterparts. No differences were found
      between the cell types in their surface expression of integrins alpha 1 beta 1,
      alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1, while
      integrins alpha v beta 1 and alpha v beta 3 appeared to be much more actively
      expressed by the anoikis-dependent population. The procedure we have proposed for
      obtaining of cell populations having closely similar origination, while differing
      in anchorage-dependent apoptosis, provides a suitable model for investigation of
      apoptotis and the role of integrins in its mechanism.

PMID- 9575617
TI  - [Effect of growth factors (BFGF and PDGF) on urokinase secretion by smooth muscle
      cells].
AB  - The dependence of urokinase (uPA) secretion on basic fibroblast growth factor
      (bFGF) and platelet-deprived growth factor (PDGF BB) was investigated by using of
      cultured rat aortic smooth muscle cells (SMC). Growth factors stimulated
      secretion of urokinase with two-phase kinetics within 1-60 minutes. Namely,
      "apparent" concentration of uPA in the conditioned media rised to 12.5 nM within
      the first 1-2 min and 5.8 nM after 30 min of cell stimulation by growth factors,
      and decreased to basal level at 5 min after stimulation of the cells. The
      character of uPA-secretion kinetics was similar in response to both growth
      factors, but the level of secreted uPA was higher in case of PDGF BB. We have
      shown that this decrease of uPA content in conditioned media is not related to
      the binding of uPA to the cell surface receptors or extracellular matrix
      proteins. One can suppose that urokinase secreted within 5 minutes could bind to
      secretory protein which nature has to be identified. But it was established that
      this secretory protein, complexing urokinase in cultured media, is not identical
      to the plasminogen activator inhibitor type 1 (PAI-1).

PMID- 9575618
TI  - [The effect of extracorporeal thermal-modified autologous plasma exchanges on
      dynamics of hormone-metabolic homeostasis indices in patients with acute
      myocardial infarction].
AB  - Changes of biochemical indexes in the blood of 56 patients with acute myocardial
      infarction against the background of conventional and complex treatment using
      plasma exchange of extracorporeal-termally modified autoplasma have been
      analysed. The findings show that complex treatment of patients with AMI, using
      plasma exchange of extracorporal-thermally modified autoplasma, leads to much
      earlier decrease of KPK, LDH, LDH-1 enzyme activity in blood; it indicates the
      reduction of the period of myocardiocyte function restoration. The usage of
      plasma exchange of extracorporeal-thermally modified autoplasma in patients with
      acute myocardial infarction is accompanied by the absence of increase of glucose
      concentration in blood (owing to the normalization of insulin production),
      favourable influence on stress-reaction of biological systems of organism
      decrease of atherogenity index. Optimisation and efficiency of AMI therapy during
      treatment in the hospital is possible, with plasma exchange of extracorporeal
      thermally modified autoplasma included in complex therapy.

PMID- 9575619
TI  - [Analysis of molecular microheterogeneity of plasma glycoproteins in a patient
      with sialidosis 1].
AB  - Using specific polyclonal monovalent antibodies, the molecular microheterogeneity
      of acute phase proteins: orosomucoid, alpha1-antitrypsin and ceruloplasmin,
      circulating in peripheral blood of a healthy donor and a patient with a
      hereditary deficiency of lysosomal neuraminidase (syalidosis I or the cherry
      stone syndrome), was analyzed by use of 2D electrophoresis. The specific
      distinctions due to a deficiency [caused by a deficiency] of lysosomal
      neuraminidase were revealed in the population of ceruloplasmin molecules, but not
      in the molecules of alpha1-antitrypsin and orosomucoid (alpha 1-acid
      glycoprotein). The molecular genetic bases of molecular microheterogeneity of
      some plasma glycoproteins and the possible use of natural models in studies of
      GP's functional role and the pathways of its transfer after internalization into
      non-hepatocytic (?) cells are discussed.

PMID- 9575620
TI  - [Two-dimensional electrophoresis of myocardial proteins in human cardio-vascular
      diseases].
AB  - The protein composition of human myocardium at some cardiovascular pathologies
      was studied by use of 2D electrophoresis. It was found that dilitation(al)
      cardiomyopathy and ischemia are both characterized by transferrin accumulation in
      myocardium and by enhanced expression of a protein with Mm 3 kD/pI 5. Besides
      that, at ischemic disease there was seen an elevation of the fetal isoform in the
      light chain of myosin. For one of the polymorphous protein systems, the
      occurrence rate changes were also recorded.

PMID- 9575622
TI  - [The clinical characteristics of panic attacks in adolescents with the cardiac
      form of the autonomic dystonia syndrome].
AB  - Peculiarities of paroxysmal course of autonomic dystonia of cardiac type were
      studied in 148 juveniles aged 14-15 years. It was found that frequency of panic
      attacks was very high, i.e. they occurred in 67-92.4% of the cases in dependence
      on severity of the disease. Panic attacks had no definite clinical picture at the
      onset. However, as the intensity of the main clinical manifestation of the
      disease (chest-pain syndrome) increased they acquired clear-cut sympatho-adrenal
      or vago-insular direction. Short duration and incomplete nels are typical for
      panic attacks in these patients.

PMID- 9575621
TI  - [Central regulatory disorders in the clinical picture of the early postoperative
      period in patients with tumors of the midbrain].
AB  - Neurological, clinical, biochemical examinations, electroencephalography,
      computer and magnetic resonance tomography of the brain of 336 patients with
      brain stem and para-brain stem tumors resulted in conclusion that nonspecific
      autonomic-endocrine reaction caused by disorders in central regulation was the
      main component of early postoperative period. The first type of such disorders
      included cases with rather stable indices of both hemodynamics and ionic-osmotic
      homeostasis characterized by favourable course. Unstable hemodynamics and
      tendency to increase of osmolarity and serum levels of sodium and glucose as well
      as unfavourable course of this period were typical for the second type.

PMID- 9575623
TI  - [The development of alcohol dependence in adolescents with personalities of the
      affective-excitable type].
AB  - Ten 13-17-year-old boys with pathocharacterologic peculiarities in premorbid
      period were examined. Syndrome of affective excitability was observed in pure
      form in 5 juveniles, while it was combined with hysteric features in 3 patients
      and with affective instability in 2 ones. These peculiarities of personality
      resulted in behavioral deviations which promoted the development of alcoholism
      and exaggerated of disorders conditioned by this disease. Course of alcoholism in
      the studied cases was unfavourable (binges, intake of large doses of alcohol and
      of the substitutes, etc) with pronounced disorders of behaviour up to aggression
      and delinquency. It was established that psychologic motivation (search of
      psychologic comfort, satisfaction of the need of actualization of personality,
      etc) played an important role both in development of the disease and in forming
      its clinical peculiarities.

PMID- 9575624
TI  - [The efficacy of lithium carbonate and Contemnol in preventing affective and
      schizoaffective psychoses].
AB  - Two groups of patients (30 patients in each group) were treated by lithium
      carbonate and contemnol. High preventive efficiency of both drugs was found:
      average annual duration of manic and depressive exacerbation as well as their
      frequency decreased practically by equal value--40-50%. The efficiency was
      somewhat higher in the group of patients treated by contemnol (80%) as compared
      with the group on lithium carbonate (70%). Total number of side-effects and
      spontaneous complaints was twice as much in prophylaxis by lithium carbonate.
      Wide application of contemnol in psychiatric practice for prophylaxis of
      aggravations (fits) of affective and schizoaffective psychoses is recommended.

PMID- 9575625
TI  - [Molecular genetic testing in the diagnosis of sporadic cases of Huntington's
      chorea].
AB  - Huntington's disease is characterized by autosomal dominant transmission and a
      complete penetrance of the mutant gene. Mutation in Huntington's disease consists
      in expansion of the unstable tandem CAG-trinucleotide repeats. This discovery
      allowed to perform a precise DNA diagnosis of the mutant gene carriers. Direct
      DNA diagnosis has a special importance in sporadic cases of the disease. We
      performed direct DNA diagnosis in 4 patients with sporadic choreic hyperkinesis,
      and elaborated a modified protocol for DNA amplification. The obtained results
      are discussed from the viewpoint of current knowledge about the nature of the
      Huntington's disease gene.

PMID- 9575626
TI  - [The dynamic changes in the cytochemical and morphological indices of erythrocyte
      function in cerebral circulatory disorders in hypertension patients].
AB  - 20 healthy individuals and 129 hypertensive patients with acute and chronic
      disorders of cerebral circulation of ischemic type were examined. It was
      established that the disease was accompanied by changes of the levels of insulin
      and cathecholamines and of cytochemical structure of erythrocytes as well as by
      alterations of carbohydrate metabolism. These changes depended on the stage of
      disorder of cerebral circulation. As far as the disease developed the changes
      became undulating reversible at first and irreversible at the late stages.

PMID- 9575627
TI  - [The indices of the thrombocyte serotonin system and of the nerve growth factor
      system in children with hereditary disorders of neuropsychic development].
AB  - Indices of both platelet serotoninergic system and the system of nerve growth
      factor (NGF) were examined in children with neurofibromatosis (15 patients),
      polygenic oligophrenia (24 patients) and Rett's syndrome (14 ones). There was an
      increase of both the level of blood serum autoantibodies (aAB) to NGF and the
      value of specific binding of 3H-imipramine (Bmax) in platelets of patients with
      oligophrenia. For this group of patients a significant negative correlation
      exists between the rate of platelet uptake of serotonin (Vmax value) and the
      degree of mental retardation (r = -0.425, p < 0.03). Decrease of both Vmax and
      activity of platelet NGF receptors was revealed in patients with
      neurofibromatosis. In such patients there was positive correlation between
      sensitivity of platelet NGF receptors to NGF (during their stimulation by test
      dose of purified NGF) and the degree of mental retardation (r = 0.697, p < 0.04).
      In patients with Rett's syndrome a significant increase of activity of platelet
      NGF receptors to NGF was observed. The conclusion was made on the existence of
      some general mechanism of intellectual defect development. Autoimmune processes
      considered to be such mechanism.

PMID- 9575628
TI  - [Changes in the level of autoantibodies to the nerve growth factor in the blood
      serum of schizophrenia patients].
AB  - A study was made of 54 patients with different forms of schizophrenia: paranoid
      (8), shift-like (30), slow-progredient (16). According to ICD-10 the rubrics
      were: F20.00 and F20.01; F20.22 and F20.02; F21 respectively. Elevation of the
      level of autoantibodies (aAB) to nerve growth factor (NGF) 1,5-fold was
      registered in blood serum of schizophrenic patients by means of enzyme
      immunoassay as compared with 70 healthy controls. The dependence of aAB level
      upon the stage of the disease development was found: in the active phase there
      was a significant increase of aAB level as compared with the patients in
      remission (1.38 +/- 0.26 and 0.92 +/- 0.25 units of optical density,
      respectively). There were no differences in respect of different forms of
      disease. The authors suggest to use aAB level as the index of the disease
      activity.

PMID- 9575629
TI  - [The epidemiological aspect of the problem of diagnosing borderline mental
      disorders].
AB  - The range of prevalence rates for borderline mental disorders is very wide: from
      17 to 210 cases per 1000 population. Considerable differences are explained both
      by a problem of detection of such patients and by certain diagnostic
      difficulties. Most clinical notions concerning borderline states are
      insufficiently definite and this has considerable influence on the results of
      epidemiologic researches. Analysis of the frequency of clinical diagnoses in two
      Moscow primary care out-patient clinics showed considerable differences which has
      disappeared under ICD-10 diagnosis.

PMID- 9575630
TI  - [The contribution of the histologist V. A. Pavlov to the study of brain
      structure].

PMID- 9575631
TI  - [A. M. Grinshtein].

PMID- 9575632
TI  - [The neuropsychological analysis of disorders of visual-gnostic functions].

PMID- 9575633
TI  - [The pathogenesis of Alzheimer's disease: the effect of aluminum ions on the
      cytoskeletal protein tubulin].

PMID- 9575635
TI  - [The plasticity of the neuromuscular synapse in pathology].

PMID- 9575634
TI  - [Peripheral nervous system function in the late period of closed craniocerebral
      trauma in Afghanistan veterans].

PMID- 9575636
TI  - [The interaction of the nervous, endocrine and immune mechanisms of the brain].

PMID- 9575637
TI  - ["Understanding", "touching" and "accompaniment" in psychiatry].

PMID- 9575639
TI  - Influence of sweet suppressing agent on gustatory brain evoked potentials
      generated by taste stimuli.
AB  - A measurement system was employed to detect gustatory evoked potentials from
      human scalp by stimulus of a taste solution with the use of a laser beam device.
      The evoked potentials for four taste qualities (i.e., sweet-sucrose, salty-sodium
      chloride, sour-tartaric acid, and bitter-quinine-HCl) were measured before and
      after treatment with a sweet suppressing agent (i.e., gymnema sylvestre extract)
      to the tongue of a human. The solution was given to the chorda tympani nerve
      located 20 mm from the apex of the tongue and 15 mm from the left side of the
      center line. The maximum potential level and its latency were evaluated.
      Artificial saliva was used as a control solution. The evoked potentials obtained
      were averaged by eight evoked potentials to detect the peak of the evoked
      potential more clearly. The latencies for taste stimuli were found on two kinds
      of peaks at approximately 50 ms and 180 ms. These peaks are P1 and P2. The
      purpose of this study is to investigate the influence of sweet suppressing agent
      on P1 and P2. The influence of the sweet suppressing agent to evoked potential by
      salty, sour, and bitter taste stimuli was not recognized, but the responses to
      sweet (sucrose) were abolished after treatment with a sweet suppressing agent. It
      was recognized that the peak P2 originated from the taste stimulus. The peak P1
      did not suffer the influence of the sweet suppression, so it was considered that
      the response to P1 was due to sensations other than the gustatory response, such
      as somatosense.

PMID- 9575638
TI  - Renal function in hyperbaric environment.
AB  - During mixed gas saturation diving (to 3-49.5 ATA) daily urine flow increases by
      about 500 ml/day, with no changes in fluid intake and glomerular filtration rate.
      The diuresis is accompanied by a significant decrease in urine osmolality and
      increase in excretion of such solutes as urea, K+, Na+, Ca2+ and inorganic
      phosphate (Pi). The fall in urine osmolality is mainly due to a reduction of free
      water reabsorption which is associated with a suppression of insensible water
      loss and the attendant inhibition of antidiuretic hormone (ADH) system. The
      increase in urea excretion may be associated with a reduction of urea
      reabsorption at the collecting duct as a consequence of ADH suppression. The rise
      in K+ excretion is due to a facilitated K+ secretion at the distal tubule as a
      result of increased aldosterone, urine flow and excretion of impermeable anions
      such as Pi. The activation of aldosterone system is partly attributed to a
      transient dehydration induced by early hyperbaric diuresis. The increase in Na+
      excretion in the face of enhanced aldosterone secretion indicates that the Na+
      transport in the proximal tubule is markedly inhibited (by unknown mechanism).
      The Pi excretion increases with no changes in plasma level of parathyroid hormone
      (PTH), thus it may be due to an inhibition of Na(+)-Pi cotransport in the
      proximal tubule. The increase in Ca2+ excretion may be secondary to the
      inhibition of Na+ transport at the proximal tubule. Precise information on the
      proximal tubular Na+ transport is important to understand the mechanisms of
      impaired solute transport under hyperbaric conditions.

PMID- 9575640
TI  - Thermophysiological significance and the role of local clothing in ambient 10
      degrees C environments.
AB  - In order to understand the role of clothing covering and uncovering the hands,
      feet, legs, thighs, buttocks and hypogastric region for human thermoregulation at
      an ambient temperature of 10 degrees C, two series of experiments were conducted
      on six healthy male subjects wearing three different kinds of clothing in Expt. 1
      and four different kinds of clothing in Expt. 2. The three kinds of clothing used
      in Expt. 1 were, clothing A covering the whole body surface area except the head,
      clothing B covering the whole body surface area except the head and feet, and
      clothing C covering the whole body surface area except the head, hands and feet.
      The four kinds of clothing used in Expt. 2 were clothing C used in Expt. 1,
      clothing D covering the whole body surface area except the head, hands, feet and
      legs, clothing E covering the whole body surface area except the head, hands,
      feet, legs and thighs, and clothing F covering the whole body surface area except
      the head, hands, feet, legs, thighs, buttocks and hypogastric regions. The
      starting time of the experiment, the subject measurement variables and the
      garments used were all kept constant throughout the experiment. The subjects were
      instructed to enter a chamber at room-temperature and various sensors were
      attached. The subjects were then instructed to relax until a quasisteady
      temperature state was reached. The subjects were then moved into a chamber at 10
      +/- 0.2 degrees C, 50 +/- 5% RH. for two hours. The main results can be
      summarized as follows: 1) The level of rectal temperatures of subjects wearing
      clothing C were maintained significantly better than the temperatures of subjects
      wearing clothing A and B who experienced a significant drop in temperature in the
      10 degrees C chamber in Experiment 1. 2) In Experiment 2, the rectal temperatures
      of subjects wearing clothing E were maintained significantly better than subjects
      wearing clothing C, D, and F, who also experienced significant drops in
      temperature in the 10 degrees C chamber. These different behavior patterns of
      rectal temperatures were discussed in terms of the counter-current heat exchange
      system.

PMID- 9575641
TI  - Oxygen kinetics in response to impulse work.

PMID- 9575642
TI  - [10th Spring meeting of the Japanese Society of Allergology. Nagoya, Japan. April
      23-25, 1998. Abstracts].

PMID- 9575643
TI  - Therapeutic efficacy of "Milgamma" in patients with painful diabetic neuropathy.
AB  - Forty-five diabetes patients with painful peripheral polyneuropathy were enrolled
      in a 3-month observational study comparing the therapeutic efficacy of Milgamma
      tablets (50 mg benfothiamine and 0.25 mg cyancobalamine) with parallel randomized
      treatment assignment with the conventional vitamin B complex treatment regimen
      Neurobex. Thirty patients in group one were randomized to receive two Milgamma
      tablets qid for three weeks followed by 1 Milgamma tablet tid for 9 weeks. In
      group two 15 patients received two Neurobex tablets tid for the entire 3-month
      study period. Therapeutic efficacy was assessed on the basis of within-patient
      differences in pain severity between Milgamma and Neurobex-treated patients and
      in vibration perception thresholds using the Rydel-Seiffer biothesiometer at
      baseline and at the end of the study. Statistically significant relief of both
      background and peak neuropathic pain was achieved in all of the Milgamma-treated
      patients and vibration perception thresholds dramatically improved with a median
      of 1.56 measured on the biothesiometer scale (t = 3.24, P < 0.01). The sensory
      symptoms improvement was insignificant in the Neurobex-treated patient group and
      the changes in the vibration perception thresholds failed to reach statistical
      significance. The therapeutic efficacy of Milgamma was greater in patients with
      early-stage diabetes as compared with those with advanced diabetic neuropathy. No
      adverse reactions were observed following the administration of the medication.
      Our results underscore the importance of Milgamma tablets as an indispensable
      element in the therapeutic regimen of patients with painful diabetic
      polyneuropathy.

PMID- 9575644
TI  - Our experience in the imaging diagnostics of abdominal aortic aneurysms.
AB  - The present study focuses on the use of imaging methods for diagnosing aneurysms
      of the abdominal aorta. We performed ultrasound tomography, computed tomography
      and digital subtraction angiography in 42 patients (17 men, 45 women, aged 25 to
      64 years) with clinically suspected aneurysm of the abdominal aorta. The results
      obtained are discussed determining the proper sequence in using these imaging
      methods in the overall diagnostic approach. The high percentage of true positive
      results (100%) achieved in digital subtraction angiography makes it the leading
      diagnostic method. It is recommended that ultrasound and computed tomography
      examinations should precede the digital subtraction angiography.

PMID- 9575645
TI  - A study on some immunological parameters in infants with salmonellosis.
AB  - The phagocytic activity of polymorphonuclears from peripheral blood (PMN) and the
      qualitative characteristic of lymphocyte populations and circulating immune
      complexes (CIC) were studied dynamically in 35 infants with salmonellosis. The
      phagocytic activity of PMNs was evaluated by phagocytic index, phagocytic number,
      the absolute phagocytic index and the nitroblue tetrazolium test. Lymphocyte
      populations were determined by immunofluoroscent assay with monoclonal
      antibodies, and CIC by precipitation with polyethylene glycol. Decreased level of
      the PMNs phagocytic activity was found in the acute phase of salmonellosis. Both
      B- and T-lymphopenia with subset dysbalance associated with greater decrease of
      T4 lymphocytes were identified. During the convalescent period the immunological
      parameters of the bacteriologically healthy infants were close to normal whereas
      the Salmonella bacteria carriers demonstrated deviations which persisted in the
      acute phase of the disease. The immunological parameters studied can be used as
      additional diagnostic and prognostic criteria in infants with salmonellosis.

PMID- 9575646
TI  - Video-assisted thoracic surgery in patients with spontaneous pneumothorax.
AB  - Following the development of video-assisted technologies and the principle of
      minimally-invasive surgery thoracoscopy has finally established itself as an
      integral part of the surgeon's armamentarium in the treatment of spontaneous
      pneumothorax. This procedure was performed on 18 patients at the Department of
      Cardio-Thoracic Surgery of the Medical University in Vienna from October 1995 to
      April 1996 and on 5 patients at the Department of Thoraco-Abdominal Surgery of
      the Medical University in Plovdiv from October 1996 to January 1997, all of which
      had been diagnosed as having complicated spontaneous pneumothorax. The main
      indications were: recurrent spontaneous pneumothorax or persistent pneumothorax
      following a five-day unsuccessful drainage of the pleural cavity. All our
      patients underwent partial parietal pleurectomy down to the level of the third
      intercostal space. Apical blebs were found in 14 patients and atypical wedge
      resection was performed. The authors used three trocars 5-12 mm in diameter. The
      thoracoscope was inserted in the fifth intercostal space in the midaxillary line.
      The other two operative trocars were inserted in the anterior and posterior
      axillary lines, respectively. The mean postoperative stay was 6 days. Our results
      support the view that video-assisted thoracic surgery is technically feasible and
      safe, associated with decreased perioperative pain and opiate requirements,
      shorter hospital stay, excellent cosmetic results, low recurrence rate, early
      return to routine activity and minimal morbidity and is therefore superior to
      conventional thoracotomy.

PMID- 9575647
TI  - Detection of Chlamydia trachomatis in first-void urine from men and women as an
      alternative to swabs.
AB  - BACKGROUND: Ideally, an effective preventive strategy for the control of
      Chlamydia trachomatis infection should take into account the following
      attributes: rapid and simple specimen collection, low cost and noninvasive test
      processing. Therefore, we compared the performance profile of urine-based
      detection of C. trachomatis antigen in first-void urine with that of testing
      urethral and endocervical samples in men and women. MATERIAL AND METHODS:
      Urethral and endocervical samples and first-void urine from 285 men and 192 women
      attending the Sexually Transmitted Diseases Outpatient Clinic at the Medical
      University in Plovdiv, Bulgaria were tested using direct immunofluorescence assay
      (DFA) (MicroTrak, Syva, Palo Alto, CA, USA). RESULTS: Seventy (25%) of all men
      tested were positive for C. trachomatis antigen in either urethral or urine
      samples. 65 men (93%) had both a positive urethral and urine sample, three men
      (4%) had only a positive urethral sample and two (3%) had only a positive urine
      sample. Thirty-five women (18%) had C. trachomatis infection. Twenty-six women
      (74%) had both a positive endocervical and urethral sample, 6 (17%) had only a
      positive endocervical sample and 3 (8%) had only a positive urethral sample. All
      women with positive urethral samples tested positive on their urine samples. Two
      of the women with a negative urethral sample and a positive endocervical sample
      had a positive urine sample. CONCLUSIONS: These results show that using direct
      immunofluorescence assay on first-void urine samples is a reliable noninvasive
      method which can replace urethral swabs in the diagnosis of C. trachomatis
      infection in symptomatic men. Urine-based strategies are also an acceptable
      alternative for the diagnosis of C. trachomatis infection in symptomatic women
      when it is not possible to obtain an urogenital sample.

PMID- 9575648
TI  - Computed tomography evaluation and three-dimensional reconstruction of facial
      trauma.
AB  - The recent development of sophisticated new techniques and the emerging of new
      therapeutic modalities underscore the limitations of conventional radiologic
      methods in the evaluation of facial trauma. The aim of this study was to evaluate
      the performance and feasibility of contemporary CT techniques in the quantitative
      assessment of soft tissue and bone injuries in patients with complex facial
      trauma. We performed examinations on 13 patients, aged 15-73 years, with complex
      facial trauma employing Sytec 3000 CT scan equipment with modern densoprofile
      software for three-dimensional reconstruction. Anatomic details--changes in
      fragment size, direction and degree of dislocation-were comprehensively
      demonstrated. Soft tissue interpositions between the fragments and luxation of
      the body of Bichat were also visualized. Three-dimensional reconstruction using
      bone and soft-tissue windowing techniques yielded valuable quantitative
      information regarding the changes in bone and soft-tissue. The process of forming
      synostosis was followed in time using densoprofile techniques. Our results
      indicate that the quantitative information gained from computed tomography with
      three dimensional reconstruction is a valuable diagnostic tool in facial trauma
      and holds promise as a cornerstone of future therapeutic strategies.

PMID- 9575649
TI  - A computed tomography method for studying the degree of postoperative aeration of
      maxillary sinuses.
AB  - Most patients with chronic odontogenic sinusitis experience aeration problems
      which remain unresolved even after classic radical antrotomy has been performed.
      The aim of this study was to create a high-yield diagnostically feasible and
      accurate CT technique which would allow the evaluation of the degree of
      postoperative changes of maxillary sinus aeration and overcome the limited value
      of traditional imaging modalities. We studied the aeration sequelae in the
      maxillary sinus following antrotomy in thirty-five patients employing Sytec 3000
      CT scan equipment with modern densoprofile software. We found a prevalence of
      62.92% for minor complications following antrotomy--a reduction in the volume of
      the maxillary sinus up to 25%, whereas the more serious complications accounted
      for 5.72%. Conventional radiologic modalities demonstrated only 25% of these
      changes. Our results underscore the importance of the densoprofile CT technique
      as a valuable and accurate diagnostic tool in detecting the changes consistent
      with the postantrotomy syndrome.

PMID- 9575650
TI  - Percutaneous ethanol sclerotherapy of autonomous thyroid nodules: preliminary
      results.
AB  - Percutaneous ethanol sclerotherapy was applied to 20 patients (17 women and 3
      men, aged 30 to 77 yrs) with autonomous thyroid nodules. The patients either were
      contraindicated because of hazardous concomitant diseases or refused surgical or
      131I treatment. Ethanol (95 alc%) was injected in 4 to 6 sessions at a mean dose
      of 0.63 ml/cc nodular tissue. Physical examination, T3, T4 and TSH assays,
      thyroid scintigraphy, sonography, and fine needle aspiration biopsy were used to
      evaluate the treatment results within a 12-month follow-up. Two months after
      ethanol injection all patients showed an improvement; in six patients the
      symptoms recurred in the 6th month. Two of them underwent a second cycle of
      ethanol injection. 12 months later an euthyroid state was maintained in 16 (80%)
      patients, while 4 (20%) did not respond to the treatment. The treatment results
      were markedly determined by the nodule size as no effect was achieved in nodules
      larger than 15-20 ml in volume. This method appears to be an appropriate and
      harmless alternative to the surgical and 131I treatment of autonomous thyroid
      nodules less than 15-20 ml in volume, especially in patients with grave
      concomitant diseases.

PMID- 9575651
TI  - Feasibility for evaluation of the efficacy of conventional ventilatory support in
      very low birth weight infants.
AB  - Morbidity and mortality analysis in prematurely born low birth weight (LBW)
      neonates, very low birth weight (VLBW) neonates and extremely low birth weight
      (ELBW) neonates forms the cornerstone in current pediatric decision-making from
      both medical and socioeconomic point of view. The successful introduction of
      artificial ventilation for neonatal respiratory failure treatment has changed
      tremendously the prognosis of many diseases with a fatal outcome. This
      retrospective observational longitudinal study was designed to evaluate the
      changes in the following main indices: mean airway pressure (MAP), oxygenation
      index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2), alveolar
      arterial oxygen gradient (A-a)DO2, ventilation index and VEI in VLBW infants
      treated with conventional ventilatory support (CV), assess the information yield
      of these indices as indicators of gas exchange at each and every one moment of
      CV, and to analyze their feasibility, accuracy and real-time convenience as
      indicators of the adequacy of inhalation therapy and their role as an
      indispensable tool in constructing the optimal treatment regimen in VLBW infants.
      Forty-seven VLBW infants requiring ventilatory support within 24 hours of birth
      were enrolled in the study. Four of the infants survived and the remaining 43
      died. The data collected were entered into a high-yield Neonatal Intensive
      Computer File and the indices were followed up sequentially and thoroughly
      analyzed as the primary outcome measures of the study. Our results show that: 1.
      The combination of indices we propose is a useful high-yield discriminating
      method for evaluating the efficacy of neonatal ventilatory support, arterial
      blood gas exchange and clinical status. 2. These indices allow early diagnosis of
      the changes in pulmonary mechanics, hemodynamics and blood saturation. 3. Using
      the combination of indices improves the diagnostic reliability and information
      yield of each one of them. 4. The twofold pattern of change of the indices in
      VLBW infants is well-recognized:--whereas a/A and OI change rapidly in the group
      of non-survivors reflecting the delicate balance in optimal gas-exchange using
      conventional methods in the survivors group there is a sustained tendency towards
      an increase in a/A values with a concomitant decrease in OI values. The airway
      pressure is constant in the presence of great fluctuations in OI values
      reflecting the breakdown in oxygenation at the high price paid for its sustenance
      in the nonsurvivors group whereas the mean airway pressure showed a gradual
      decrease in the survivors group and allowed early weaning from mechanical
      ventilation. (A-a)DO2 remained high in the non-survivors group thus reflecting a
      high-degree, practically constant shunting whereas the same index showed a
      tendency towards decrease in the survivors group. 5. These indices allow optimal
      management of neonatal ventilation and oxygenation and timely correction or a
      change of the ventilatory or/and oxygenation strategy. 6. This information forms
      the basis for prognostic conclusions regarding the current status or the survival
      of the neonates.

PMID- 9575652
TI  - Population morbidity in a community with nitrate contamination of drinking water.
AB  - The population morbidity assessed according to ICD-9 was studied in the village
      of Karadzhalovo, the district of Plovdiv, where concentration of nitrates in
      drinking water was constantly above the tolerable level. The observation was
      carried out within a 5-year period (1990-94). The data were compared with those
      from a control village in the same district. Nonparametrical analysis was used to
      make a comparative analysis of the disease incidence in both communities for the
      observed period. Significant statistical differences were found between the
      morbidity in the experimental and the control villages.

PMID- 9575653
TI  - An algorithm of diagnostic-therapeutic invasive sonography.
AB  - The present study describes an algorithm of diagnostic-therapeutic invasive
      sonography that was used in 276 patients. 276 manipulations using ultrasound
      guidance were performed on 371 objects. These include therapeutic punctures
      (evacuations and drug applications), percutaneous nephrostomies and dilatational
      minilaparatomy with drainage system. We achieved complete therapeutic success in
      77.5%, partial therapeutic success in 14.1% and failures only in 8.4%. These
      satisfactory results indicate that the developed algorithm makes possible the
      individual approach to the patient, allows correct choice of technique, method,
      and strategy; it helps to achieve the therapeutic target as well to include a
      diagnostic element at a certain stage of the therapeutic process.

PMID- 9575654
TI  - A method for polyvalent analysis of preventive motivations.
AB  - The article presents a method for polyvalent analysis of preventive motivations
      (MPAPM). The method is applied by using the survey technique with a specially
      designed for the purpose questionnaire. Four types of data are gathered and
      analyzed: social-adaptive indicators, health status, attitude toward prevention
      and actual choice. MPAPM provides the opportunity to achieve fundamental
      scientific results in the study of the motivations underlying risk behaviour.
      Another application of the method is the detailed study of the theoretical and
      practical aspects of preventive motivations, both in the community and on an
      individual level--for evaluating the eventual success rate of a particular
      individual attending preventive programs. It is possible to analyze the
      potentials of prevention compared to alternative methods of improving one's
      health status. Juxtaposing conscious motives and actual behaviour, MPAPM enables
      the researcher to analyze the role of the unconscious aspects of preventive and
      risk behaviour. MPAPM employs new types of concepts which define the adaptive
      aspects of disease, health, social status and prevention. In its essence this is
      a method for marketing study of the polyvalent nature of the need for prevention
      (combined and concurrent interaction of social, psychological, epidemiological
      and biological factors).

PMID- 9575655
TI  - A study on the aerobic intestinal microflora in patients with salmonellosis and
      shigellosis.
AB  - Human intestinal microflora provides substantial protection of the body against
      intestinal pathogens and affects the course and outcome of intestinal infections
      with diarrheal syndrome. We studied the aerobic intestinal microflora in 120
      patients with salmonellosis and 60 patients with shigellosis. Intestinal
      microflora was determined qualitatively assessing the relative share of E. coli
      and other aerobic representatives of the potentially pathogenic microorganisms.
      Disturbances of the aerobic intestinal microflora were found in 76% of the
      patients with salmonellosis and 80% of the patients with shigellosis in the acute
      stage of the disease. They occurred more commonly and were graver in the severe
      clinical forms of intestinal infections. Their frequency in convalescent
      bacterial carriers was greater.

PMID- 9575656
TI  - Acute renal failure--etiologic and therapeutic considerations. A five-year
      experience at a single institution.
AB  - In the present study we highlight the epidemiology, etiologic spectrum, and
      evaluation of ARF in adults. We then expand on the pathophysiologic mechanisms of
      renal failure and discuss the rationale for current therapeutic strategies in ARF
      patients. A total of 79 patients (45 male, female 34), aged 18-75 years (median
      age 51.2 +/- 17.7 years) with acute renal failure were studied in 5 years
      (January 1990 through October 1995). Emergency hemodialysis sessions following an
      acute anuric episode were instituted in 39 cases (49.3% of all patients). The
      median number of hemodialysis procedures per patient treated at our institution
      was 3.2 +/- 1.9. The total number of acute interstitial nephritis-associated ARF
      was 40. In 30 of them (75%) the acute renal insult included a combination of
      several therapeutic antimicrobial agents, in 2 cases (5%) ARF followed the
      administration of nonsteroidal anti-inflammatory drugs, in 1 (2.5%) it resulted
      from a combined therapeutic regimen and in the remaining 5 (12.5%) from the
      application of a single drug. Acute interstitial nephritis developed in 2
      patients following a viral infection. In the hemodialysis-treated ARF group 12
      patients (29.77%) had interstitial nephritis and 2 patients (5.13%) presented
      with renal impairment for an unspecified period of time preceding the development
      of overt ARF. In a subset of this group of patients, ARF occurred in 7 patients
      (17.95%) following an urologic intervention, in 8 patients (20.51%) as a
      consequence of thermal or mechanical trauma or intoxication and in 3 cases
      (7.69%) it resulted from fever of unknown origin. Three patients with
      postoperative peritonitis and 4 other (10.26%) with postoperative complications
      were encountered in our series. No cases of septic abortion-related or obstetric
      related ARF were recorded. 92.3% of all hemodialysis-treated patients seen at our
      Institution had received a combination of antibiotics and only 2 patients had
      been pre-treated with a single antimicrobial agent. Our results underscore the
      strong tendency towards diversity in the etiologic spectrum of clinical entities
      causing ARF and the increase in the number of acute interstitial nephritis. These
      factors highlight the importance of precise dosing and administration of drugs,
      especially antibiotics, as well as the duration of antibiotic treatment.

PMID- 9575657
TI  - [Polymorphism of group specific component (Gc) in nine Han subpopulations in
      China].
AB  - Isoelectric focusing (IEF) followed by immunofixation in thin layer
      polyacrylamide gels (pH4-6) was used to analyse the Gc subtypes of 1841
      individuals from nine Han geographically distributed populations in China. The
      Gc1F gene frequencies in these Han subpopulations from Lanzhou, Huhhot, Harbin,
      Xi'an, Zhengzhou, Chengdu, Guiyang, Zhangzhou and Harras in Guangdong Province
      were 0.3905, 0.4333, 0.4193, 0.4146, 0.4182, 0.4035, 0.4045, 0.4381 and 0.4347
      respectively; Gc1S were 0.3071, 0.2190, 0.2734, 0.2261, 0.2182, 0.2871, 0.2889,
      0.2738 and 0.2764 respectively; Gc2 were 0.2786, 0.3357, 0.2917, 0.3367, 0.3295,
      0.2896, 0.3065, 0.2667, and 0.2814 respectively. GcV were 0.0238, 0.0119, 0.0156,
      0.0226, 0.0341, 0.0198, 0.0000, 0.0214 and 0.0075 respectively. The results of
      present study indicated a clear cline of linear change from north to south China
      in allelic frequency at the Group-Specific Component (Gc) locus among nine
      Chinese populations. Three alleles, Gc1F, Gc2 and GcV, showed frequencies varying
      from 0.3905 to 0.4381, from 0.2786 to 0.3367 and from nil to 0.0341,
      respectively, over these geographical subpopulations. In addition, some rare
      variant phenotypes of Gc in Chinese populations were discussed.

PMID- 9575658
TI  - [Novel mutations identified in exon 7 of phenylalanine hydroxylase gene in
      Chinese].
AB  - Exon 7 of the phenylalanine hydroxylase (PAH) gene was analyzed in 45 children
      affected with classic phenylketonuria (PKU) from northern China by using PCR
      single strand conformation polymorphism (PCR-SSCP) technique and DNA direct
      sequencing. Six missense mutations (i.e. R243Q, R241H, G247V, L249H, P254I and
      G257V) and one silent mutation (V245V) were identified. The latter three missense
      mutations were demonstrated as novel mutations in comparison with the PAH
      mutation Database. One missense mutation (R241H) was first documented in Chinese.
      Our results showed population and regional differences in the PAH mutation
      distribution and suggest that there is more than one founding population for PKU
      in China. The finding of novel mutations will enhance our capability in molecular
      diagnosis of PKU.

PMID- 9575659
TI  - [A new karyotype of Drosophila albomicans].
AB  - In the paper, we present a new karyotype of D. albomicans found in the
      populations from Southeast China. Short chromosome IV of D. albomicans has been
      reported in Thailand populations while long type was discovered in Taiwan
      populations. However, we found that long and short chromosome IV coexisting in
      the same somatic cells. The individuals which contained the "hybrid" cells were
      collected from Shanghai, Fuzhou, Xiamen and Shenzhen, China. Moreover, the three
      karyotypes could be detected in each population mentioned above in other words,
      the populations showed a pattern of karyotype polymorphism. Furthermore, our
      observation disclosed that the new karyotype was unstable. Its frequency
      decreased with increasing breeding generation. Since the geographic locations of
      these populations just lies between the regions of double long and double short
      type's populations, this new karyotype seems a intermediate transitional type
      during the variance process of D. albomicans.

PMID- 9575660
TI  - [Construction of yeast ADH2-SUC2 hybrid promoter and its regulation in gene
      expression].
AB  - By fusing the upstream activation sequence (UAS) of ADH2 gene to the 5' end of a
      series of deletions in the upstream region of SUC2 gene, 4 expression plasmids
      YFD110 delta 1, YFD110 delta 9, YFD110 delta 17 and YFD110 delta 11 were
      constructed. They contained different hybrid promoters for transcription of SUC2
      gene. After transforming them together with two control plasmids YFD26 delta 1,
      YFD25 into yeast. S. cerevisiae Y33 respectively, the transformants were grown in
      the repression or derepression media and the invertase produced by each
      transformants were analyzed by colormetry and gel electrophoresis. The results
      were as follow is: (1) UASSUC2 and UASADH2 in the hybrid plasmid YFD110 delta 1
      worked synergically under derepression condition. Under repression condition,
      Y33/YFD110 delta 1 produced very low level of glycosylation invertase. (2)
      Compared with three different derepression media, the medium containing low
      concentration glucose gave higher derepression efficiency of glycosylated
      invertase than the media containing glycerol and ethanol.

PMID- 9575661
TI  - Some historical notes and remarks on prevention in environmental and occupational
      health.
AB  - Throughout history, there are many illustrations showing more or less rational
      efforts to avoid disease, but preventive measures have often been, and still are,
      neglected or even counteracted for economic reasons. Some examples of early
      preventive actions are given along with illustrations of how the increasing
      knowledge through epidemiological and other research has created a foundation for
      adequate decisions to the benefit of health protection, although frequently taken
      after much discussion and considerable time-lag from the first evidence of a
      particular health risk. There is also an inherent problem in successful health
      protection since both public and political support for the issue might get lost
      along with the scientific activity and knowledge in the field.

PMID- 9575662
TI  - The effect of depletion of the earth ozone layer on the human health condition.
AB  - Development of economic human activity has caused many harmful side effects which
      constitute an important danger for the biological life of our planet. This review
      discusses some aspects of the atmospheric changes and their influence on UV
      radiation reaching a man. The ozone-layer depletion is the result of emissions to
      the atmosphere chemical substances containing chlorine and bromine. Ozone, which
      absorbs the solar ultraviolet radiation, is a basic bio-protective filter.
      Degradation of the atmospheric ozone layer leads to increase of UV-level in our
      environment. The harmful effects of UV-radiation on live organisms constitute a
      danger for health of the whole human population. There is no doubt that
      cumulative exposure to UV radiation is important in the aetiology of skin cancer.
      A strong cataractogenic effect of UV radiation has been also evidenced. It is
      also known that the increase of UV radiation may be capable of activating viruses
      and reduce immunological response. The recent and predicted increase in these
      menaces are discussed.

PMID- 9575663
TI  - The distribution and excretion of hexabromobenzene after a single administration
      in rat.
AB  - The aim of this study was to investigate the disposition of [1-14C]
      hexabromobenzene (HBB) in rats. The experiments were performed on 76 female
      Outbred IMP: Wist rats with body weight of 200 g +/- 20%. The compound was given
      orally in a single dose of 600 mg/kg and 4500 mg/kg. 14C radioactivity was traced
      in selected tissues, blood, urine and faeces, 0-72 hours following the
      administration. Maximum concentration of the 14C in blood was observed during the
      2nd hour after the compound administration. The accretion of 14C in plasma
      proceeded with kinetic constant of 1.35/hour, whereas 14C-decline was biphasic.
      Half-lives for phase I and II were 1.2- and 440 hours, respectively. No
      substantial differences were noted in relation to the HBB dose. In tissues the
      highest radioactivity was observed in the fat tissue, adrenals and sciatic nerve.
      About 16 to 24% of the administered radioactivity was still retained in the rat
      body, 72 hours after administration of the compound. Faeces turned out to be the
      main route of excretion (about 75% of the given dose); only 1% was excreted in
      urine. Following on the literature data and our total balance of 14C elimination
      with faeces, we concluded, that almost 70% of 14C found in the faeces were
      composed of other metabolites than HBB and its lower-brominated derivatives. The
      above data indicate that HBB, especially in the case of chronic exposure, might
      accumulate in the body.

PMID- 9575664
TI  - Persisting behavioural and electroencephalographic effects of exposure to
      chlorphenvinphos, an organophosphorous pesticide, in laboratory animals.
AB  - Organophosphorous compounds (OPs) constitute a large proportion of insecticides
      used all over the world. Their insecticidal properties and acute toxicity in
      nontarget species derive from the inhibition of acetylcholinesterase (AChE) which
      disturbs the cholinergically mediated neurotransmission. OPs do not accumulate in
      living organisms and the acute signs and symptoms disappear as the AChE activity
      returns to normal level. Therefore, they are regarded as relatively safe.
      However, as some literature data suggest, after either acute or prolonged
      exposure to OPs subtle neurobehavioral impairments may persist long after
      normalization of AChE activity. The possibility that OPs exposure may induce such
      long-term effects is nowadays a problem of great concern for the regulatory
      agencies. Here we present a review of studies from our laboratory aimed at
      detecting neurobehavioural effects of exposure to chlorphenvinphos, an OP
      pesticide ((2-chloro-1-(2,4-dichlorophenyl) vinyl diethyl phosphate)--CVP)) in
      laboratory animals. In Poland, CVP is manufactured (250 tons/year) and used for
      crop protection. In a series of experiments we have demonstrated that: a) in
      rabbits, two i.p. exposures to CVP at the same sublethal dose at three-month
      interval resulted in a similar inhibition of blood AChE activity but the effect
      of the second exposure on body temperature and hippocampal EEG was smaller and
      less consistent than that of the first one. This would indicate that some
      permanent changes within the CNS may occur even after a single exposure to CVP;
      b) in rats, under conditions of repeated i.p. exposure to CVP (one injection/day
      for ten days) at a symptomatic (3.0 mg/kg) dose inhibiting blood and brain AChE
      activity by about 80%, the tolerance to CVP, assessed from the spontaneous
      locomotor behaviour, developed within four to five days. However, single exposure
      to CVP at a symptomatic (3.0 mg/kg) or subsymptomatic (1.0 mg/kg, less than 50%
      AChE inhibition) dose, or repeated exposure (one injection/day, for ten days) at
      subsymptomatic doses (1.0 mg/kg or 0.5 mg/kg) resulted in subtle changes in
      complex behaviours detectable after AChE activity in blood and in the brain had
      returned to the normal level. The changes--neophobia in the open field, an
      increased and more persistent emotional response to a stressful stimulus, and
      increased EEG arousal response to an external pain signalling stimulus--suggest
      an increased reactivity of the system or systems responsible for the induction of
      fear; c) direct intrahypothalamic injections of CVP, unlike those of
      oxotremorine, a direct stimulant of cholinergic muscarinic receptors, did not
      induce overt changes in the animal (rabbit) behaviour and EEG. This would
      indicate that the changes in the CNS functions after CVP exposure may be the
      consequence of increased cholinergic activity due to AChE inhibition rather than
      to a direct stimulation of cholinergic muscarinic receptors by CVP. The above
      findings provide experimental evidence that health effects of exposure to CVP,
      may persist after recovery of AChE activity in blood and in the brain.

PMID- 9575665
TI  - Influence of tobacco smoking on metallothionein isoforms contents in human
      placenta, amniotic fluid and milk.
AB  - SDS-PAGE was used for separation of heat-stable proteins in placenta, amniotic
      fluid and milk of women who smoke actively and those exposed to tobacco smoke
      (passive smokers). In the number of protein bands stained with Coomassie
      brilliant blue R-250, several bands were stained with silver nitrate. The
      presence of low-molecular band with molecular weight of 6.5 kDa, corresponding to
      the mobility of electrophoretic MT-1 was detected in placenta, amniotic fluid and
      milk. The involvement of MT-2 isoform was much lower, although more evident in
      amniotic fluid and milk of active smokers. In this group of women an enhanced
      concentration of the band with molecular weight of 25-30 kDa was observed in
      placenta, colostrum and milk on the second day after delivery; several protein
      bands emerged in the area of the same mobility in amniotic fluid; the presence of
      the band with molecular weight of 12.5 kDa and the absence of protein bands of 25
      30 kDa were found in milk excreted on the third day post partum. Our results show
      the apparent differences between proteingrams of placenta, amniotic fluid and
      milk of active and passive smokers.

PMID- 9575666
TI  - Death at sea: certain factors responsible for occupational hazard in Polish
      seamen and deep-sea fishermen.
AB  - Deaths at sea, namely work-related fatal cases, are registered in all fleets
      throughout the world. Considering the medical and legal aspects, they are subject
      to notification, inquest, and possible indemnity. The aim of the study was to
      identify causes, circumstances, and mortality rates among Polish seamen and deep
      see fishermen. The group studied comprised 113,260 employees of one shipping
      company and two fishing enterprises. Out of this number 148 fatal cases (109
      seamen and 39 fishermen) registered during the years 1985-94 were investigated
      thoroughly. Mean annual rates of mortality (130.6) and fatal accidents (67.8)
      were calculated per 100,000 employees. They occurred to be higher than those
      among fishermen and the male population of the same age group (20-59 years)
      employed in various branches of the land economy, yet remaining lower compared to
      data on British and American seamen and fishermen. The risk of death was
      particularly high in persons above 40 years of age. It was demonstrated that
      unlike in the general population, 52% of deaths were due to external causes;
      primarily sea catastrophes, injuries, poisoning and missing. Among internal
      causes, circulatory diseases accounted for over 80% of deaths, including one
      fifth of cases due to acute myocardial infarction. In one third of these cases,
      cardiac failure had been already diagnosed before the voyage. The following
      circumstances were specific to deaths occurring during the voyage: deaths at open
      sea, frequently in the state of being alone in the cabin, no possibility of
      evacuating sick person to land medical institution, limited access to qualified
      medical assistance and effective rescue from outside, poor life-saving facilities
      and difficult communication. It was indicated that in a substantial percentage of
      fatal cases an adverse effect of the work performed, navigation and weather
      conditions proved to be hazardous, life-threatening and responsible for the fatal
      outcome. Sixty per cent of deaths were acknowledged by the shipowners as work
      related or equivalent accidents with legal and economic consequences. The
      countermeasures proposed by the authors to minimize health hazards and life
      threat at sea are of rather limited value for both organizational and economic
      reasons. The ship is still considered as one of the most dangerous workplaces.

PMID- 9575667
TI  - Pulmonary manifestations in cement workers in Jordan.
AB  - Respiratory symptoms and pulmonary function were studied in a cross-sectional
      survey of 348 Portland cement workers in Jordan. The workers were differently
      exposed to dust for at least 3 years. The geometric means +/- SE of respiratory
      cement dust concentrations were 0.5 +/- 2.1, 1.6 +/- 2.61 and 3.9 +/- 4.02 mg/m3
      in the three determined levels of exposure, respectively. About 42% of the
      workers reported various chronic respiratory symptoms, but cough, dyspnea, and
      asthma were most prevalent (18.7%, 17.5% and 15.8%, respectively). The prevalence
      of respiratory symptoms did not tend to increase with tenure. Asthma was
      significantly associated with the age of 30-39 years and showed a proportionate
      association with exposure level. Smokers had higher rates of symptoms than non
      smokers. Rates of cough, phlegm, and wheeze increased proportionally to the
      number of cigarettes smoked per day. Overall pulmonary function indices were
      normal. When the independent variables were fit into a regression model, age
      significantly affected FEV1/FVC and current smoking affected FEF25-75%. It is
      concluded that inhalation of cement dust irritates the respiratory tree without
      markedly affecting lung function, and smoking aggravates this effect.

PMID- 9575668
TI  - Rhythm patterns of basic brain bioelectric activity in workers chronically
      exposed to carbon disulfide.
AB  - The work aimed at defining the pattern and frequency of rhythm disturbances in
      basic brain bioelectric activity in EEG recordings, routinely regarded as normal,
      in workers exposed to chronic carbon disulfide (CS2) poisoning, without detected
      symptoms of organic lesions in the nervous system. The study covered 188 viscose
      spinners occupationally exposed to changing concentrations of CS2 vapours whose
      mean annual results of measurements ranged between 10 and 35 mg/m3, and the mean
      individual exposure fell within the range of 9.9-41.6 mg/m3 (mean--25.8 mg/m3).
      The frequency of alpha rhythm was analysed in EEG recordings with exclusive or
      nearly exclusive alpha rhythm in two groups studied. The presence or absence of
      subjective symptoms was taken as a criterion for the selection of subjects. Group
      I was composed of 116 subjects with subjective symptoms. Group II consisted of 72
      workers with neither subjective nor objective symptoms. The age in group I ranged
      from 26 to 65 years (mean, 48.7 years), and the duration of employed from 5 to 39
      years (mean, 23.3 years). The complaints reported were of neurasthenic and
      polyneuropathic type. The age in group II ranged from 28 to 63 years (mean, 49.4
      years), the duration of occupational exposure accounted for 8-43 years (mean,
      25.6 years). The control group included 194 persons with EEG routinely regarded
      as normal, matched by gender, age and work shift distribution. The subjects in
      Group I reported most frequently the following complaints: headache (72.4%),
      vertigo (48.3%), increased emotional irritability (42.2%), dysmnesia (36.2%),
      sleep disorders (27.6%), concentration difficulties (25.9%), limb pains (36.2%)
      and paraesthesia (27.6%). In the groups of subjects chronically exposed to CS2,
      both with subjective neurological symptoms, and without subjective or objective
      neurological symptoms, EEG recordings, routinely regarded as normal, did not
      reveal constant and symmetrical frequency of alpha rhythm waves. EEC recordings
      in the CS2 exposed workers with subjective neurological symptoms revealed almost
      constant frequency (12.9%) or slightly fluctuating frequency (41.4%) in 54.3% of
      subjects. In 45.7% of subjects considerable fluctuation of alpha rhythm frequency
      at the range of 3-4 Hz was found. Frequency disturbances applied to both sides,
      however, they were more pronounced in the leftside leads. Statistical analysis
      showed, neither in Group I nor in Group II, significant relationship between the
      pattern of alpha rhythm frequency fluctuations, the duration of CS2 exposure and
      the cumulative exposure index. Substantial and asymmetric fluctuations of alpha
      rhythm frequency found in the exposed group of subjects with subjective symptoms
      were considered as subclinical disturbances in the function of the central
      nervous system.

PMID- 9575669
TI  - Measurements of click-evoked otoacoustic emission in industrial workers with
      noise-induced hearing loss.
AB  - Click-evoked otoacoustic emission (c-EOAE) was analysed in a group of 122 males
      (= 244 ears) occupationally exposed to industrial noise levels of 89-94 dB (A).
      The highest intensity of cochlear responses was observed at 1 and 2 kHz, while at
      the higher frequencies (3-4 kHz), c-EOAE spectrum was contracted proportionally
      to the level of the hearing loss and duration of occupational exposure to noise.
      If hearing loss in pure-tone audiometry exceeded 30 dB HL at 1 kHz and 40 dB at 2
      and 4 kHz, c-EOAE was absent. The analysis of the relationship between c-EOAE
      spectrum and hearing threshold in pure-tone audiogram showed correlation (R =
      0.43 to 0.48, at p < 0.01) between distribution of emission energy and hearing
      threshold at the same range of frequencies. It was found that the c-EOAE
      amplitudes as well as the values of c-EOAE energy in the noise-exposed people
      were lower by about 3 dB SPL than in the controls, especially at 4 kHz even in
      cases of pure-tone hearing thresholds < or = 20 dB HL. This study indicates that,
      owing to c-EOAE, it is possible to detect a slight noise-induced cochlear lesion
      which may be overlooked in pure-tone audiometry.

PMID- 9575670
TI  - Environmental and occupational health during social transition in central and
      eastern Europe. Selected fragments of the eighth annual symposium. May 26-31,
      1997, Blagoevgrad, Bulgaria.

PMID- 9575671
TI  - British-Polish symposium on noise induced hearing loss. November 20-22 1997, Slok
      n/Lodz, Poland.

PMID- 9575672
TI  - Occupational medicine in Polish journals of 1996. Part 2.

PMID- 9575673
TI  - Occupational medicine in eastern journals of 1996. Part 2.

PMID- 9575674
TI  - The vascular space-like structure in melanocytic nevus is not an injection
      artifact: report of a case and an experimental study.
AB  - Melanocytic nevi may microscopically associate with clefts or slits of the nests
      resembling lymphatic or vascular spaces. This unique histologic feature has been
      known as an artifact of injection or tissue-processing. We present a case of
      melanocytic nevus with a prominent vascular space-like structure. We also studied
      whether intralesional injection of local anesthetic could reproduce similar
      histologic findings. A 45-year-old Japanese female visited us with a solitary,
      brownish papule on the chest. Histology revealed numerous nests composed of round
      to oval-shaped nevus cells throughout the entire dermis. In the mid-dermis, nevus
      cells were lined up in a layer anastomosing and forming a vascular space-like
      structure. These nevus cells were uniformly stained with vimentin and S100
      protein but not with factor VIII-related antigen. They were also positively
      immunoreactive with anti-type IV collagen and anti-fibronectin. There were no
      significant differences in staining intensity in the nevus cells between the
      solid portion and the vascular space-like structure. In the experimental study,
      eight melanocytic nevi were removed under local anesthesia. The local anesthetic
      solution was then injected into the excised nevus. Intralesional injection of a
      considerable volume of local anesthetic was capable of causing slits or clefts of
      the nests and dermal edema; however, it failed to reproduce a vascular space-like
      structure similar to that in the present case. These findings suggest that a
      vascular space-like structure in melanocytic nevus is not caused by the injection
      alone. Some other factor(s) may play a major role in the development of such
      structures in melanocytic nevus.

PMID- 9575675
TI  - A large number of tandem repeats in the polymorphic epithelial mucin gene is
      associated with severe acne.
AB  - Polymorphic epithelial mucin (PEM) or MUC1 is a glycoprotein secreted from
      various epithelial gland tissues. In skin, PEM is detected in sweat glands and
      sebaceous glands by the DF3 monoclonal antibody. The gene of PEM includes an
      allele exhibiting length polymorphism due to a variable number of tandem repeats
      (VNTR); this is expressed co-dominantly, which may influence the microenvironment
      of the skin. The allelic size variation of the PEM gene was investigated in
      Japanese acne patients, atopic dermatitis patients, and healthy controls. The
      frequency of longer length alleles was significantly higher in severe acne
      patients.

PMID- 9575676
TI  - Pruritic skin diseases in the elderly.
AB  - A total of 149 elderly men and women with pruritic skin problems were selected
      for study at the dermatological clinic in the Department of Medicine, Rajavithi
      General Hospital, Bangkok, Thailand, from 26 November 1996 to 10 January 1997.
      There were 62 men (41.6%) and 87 women (58.4%). The average age was seventy
      years. Among these elderly patients, pruritic skin disease was the most common
      problem, found in about 41%. Xerosis (senile pruritus) was the most common
      problem at 38.9%. Other pruritic skin diseases found were inflammatory eczema
      (22.8%), lichen simplex chronicus (12.1%), skin infections (11.4%), psoriasis
      vulgaris (6.7%), urticaria (4.7%), drug rash (2%), insect bite (0.7%), and
      anogenital pruritus (0.7%). Xerosis usually occurred with increased bathing
      frequency and use of strong soaps and detergents. The causes of inflammatory
      eczema were seborrheic dermatitis, allergic contact dermatitis, dyshidrosis, and
      stasis dermatitis. Statistical analysis of xerosis and inflammatory eczema by
      gender showed no difference, but there was more inflammatory eczema among
      females.

PMID- 9575677
TI  - HLA antigens and linkage disequilibrium patterns in Turkish Behcet's patients.
AB  - Behcet's disease (BD) is a multisystem disorder featuring mucocutaneous, ocular,
      articular, vascular, intestinal, pulmonary, and neurologic involvement. Although
      the pathogenesis of the disease is still unknown, most studies have proposed that
      immunologic factors may play a major role in its development in genetically
      predisposed individuals. Seventy-one Turkish patients with BD, diagnosed
      according to the International Study Group for Behcet's Disease criteria, were
      studied and compared with 600 healthy controls to determine not only frequencies
      of HLA-A, B, and DR antigens but also whether BD shows any distinct linkage
      disequilibrium (LD) patterns. In addition, three-point linkage disequilibrium and
      relative risk (RR) values were determined. Of the HLA-A, B, and DR antigens
      examined, only B5 (51) was significantly increased in the patient group (X2 =
      55.4; p < 0.05; RR = 6.44). DR7 was significantly decreased in the patient group
      (X2 = 6.9; p > 0.05; RR = 0.31). HLA haplotype B5-DR5 was found to be in negative
      LD in the control group, but Behcet's patients showed a strong positive LD
      between these two antigens. HLA haplotypes A2-B12, B5-DR2, and B12-DR4 showed
      negative LD in the patients; A1-B5 and B5-DR5 had positive LD in the patients.
      HLA haplotype A2-B5-DR5 was found to be more frequent than expected in both
      patients and control groups. A2-B12-DR4 showed a negative LD in the patients. The
      strong LD patterns between HLA-B and DR antigens in BD suggest that the
      susceptibility gene to BD could reside between the these two antigens.

PMID- 9575678
TI  - A Japanese case of Neu-Laxova syndrome.
AB  - A 5-day-old Japanese female with Neu-Laxova syndrome was presented. The patient
      had severe edema throughout the body, desquamation, and erosion of the skin. She
      also exhibited microcephaly, exophthalmos, and rocker-bottom feet. Histologic
      examinations of a cutaneous specimen showed atrophy of the dermis and absence of
      the sebaceous glands. These represent embryonic abnormalities. Even though there
      was no hypoplasia of the cerebellum and lungs or hydramnios, we evaluated this
      patient as the first Japanese case of this sporadic disease. With intensive care,
      including dermatological treatment, the patient survived for 134 days.

PMID- 9575679
TI  - Recurrent annular erythema in a case of seronegative Sjogren's syndrome.
AB  - We describe a case of Sjogren's syndrome who repeatedly developed annular
      erythema on her extremities. Her anti-nuclear antibody, anti-SSA/Ro antibody, and
      anti-SSB/La antibody were all negative. Characteristics of the annular erythema
      included a tendency to appear on the extremities especially in summer,
      spontaneous regression after 1-2 weeks, and residual slight pigmentation. The
      histological findings revealed dermal perivascular lymphocytic infiltration
      admixed with some neutrophils. Slight exsudative changes were found in the upper
      dermis. There were no epidermal changes. This case suggests the existence of
      annular erythema which may not be related to the anti-SSA/Ro or anti-SSB/La
      antibody. Unknown factors other than those antibodies may be involved in the
      pathogenesis of the annular erythema.

PMID- 9575680
TI  - The analysis of mRNA expression of cytokines from skin lesions in Churg-Strauss
      syndrome.
AB  - We report our recent clinical experience with a patient suffering from Churg
      Strauss syndrome and the results of our investigation into the mRNA expression of
      cytokines in the patient's lesions as well as in the frozen sections from a
      previous patient. In both cases, blood IgG was at a high level. Cytokine mRNA
      expression differed according to the degree of cellular infiltration. In the
      presence of marked infiltration, counteracting Th1 and Th2 cytokines were
      simultaneously detected; the former included IL-12 and IFN-gamma, and the latter,
      IL-6 and IL-10. The concurrence of both types of cytokine could be attributed to
      several factors. For example, IL-6 is involved through some mechanism in the
      formation of immune complexes by IgG, and IL-12 and IFN-gamma appeared to
      participate in the development of granuloma. These suppositions support the
      suggested immunological etiology of the disease. It is also inferred that the
      dominance of one of the two types of cytokines depends on the clinical phase of
      the disease.

PMID- 9575681
TI  - HIV-associated eosinophilic pustular folliculitis: successful treatment of a
      Japanese patient with UVB phototherapy.
AB  - We report the successful treatment with ultraviolet B phototherapy of a patient
      with HIV-associated eosinophilic pustular folliculitis. We were able to observe
      the clinical and therapeutic course for about one year and three months. This 35
      year-old homosexual Japanese man presented with disseminated, discrete,
      follicular, erythematous papules with intense pruritus over his face, neck, chest
      wall, and upper back. Initially, the eruption responded to therapy with topical
      or oral indomethacin and oral H1 antihistamine. However, the eruption was highly
      prone to recurrence, and it gradually failed to respond to these therapies. The
      eruption became chronic and persistent and manifested the excoriated, prurigo
      like nodules that are typical of reported pruritic papular eruption, suggesting
      that this skin disease and HIV-associated eosinophilic pustular folliculitis are
      two forms of the same disease entity. UVB phototherapy in small doses was very
      effective for the persistent eruption, and no recurrence of the eruption was
      noted during or since the six-month maintenance therapy (once a week at a dose
      equivalent to 0.75 of the minimal erythema dose) (9 months total). No unfavorable
      side effects have been observed during or after the UVB phototherapy (cumulative
      UVB doses of 2,320 mJ/cm2).

PMID- 9575682
TI  - Ofuji papuloerythroderma associated with follicular mucinosis in mycosis
      fungoides.
AB  - Ofuji papuloerythroderma is a distinctive clinical entity of unknown etiology,
      which may occasionally be associated with B cell and T cell lymphoma or visceral
      malignancy. We report a case of papuloerythroderma associated with follicular
      mucinosis in mycosis fungoides (MF) that raises the possibility of
      papuloerythroderma as a form of prelymphomatous skin eruption. This specific
      papuloerythroderma responded well to the Re-PUVA treatment, which is a
      combination of etretinate and PUVA photochemotherapy.

PMID- 9575683
TI  - A case of cutaneous Ki-1 positive anaplastic large cell lymphoma in a
      hemodialysed patient.
AB  - A 66-year-old woman who suffered from chronic glomerulonephritis had been
      undergoing hemodialysis for about 10 years. A reddish papule on her waist
      developed gradually into a nodule (1.9 x 1.4 cm). Histopathological findings
      showed that the tumor cells had oval to reniform nuclei; multinucleated
      neoplastic cells and erythrophagocytosis were also present. Immunohistochemical
      analyses revealed that the membranes of the tumor cells stained for Ber-H2 (Ki-1)
      and epithelial membrane antigen (EMA), Vimentin was partially positive, but
      keratin, S-100, chromogranin, leukocyte common antigen (LCA), UCHL-1, MT-1, L-26,
      MB-1 and C3D-1 were all negative. Anti-human T-cell leukemia virus-1 (HTLV-1) was
      also negative. No gene rearrangement of the T-cell receptors beta-, gamma- and
      delta-chain could be detected. From these results, we diagnosed cutaneous Ki-1
      anaplastic large cell lymphoma (ALCL), but the origin could not be determined.
      The relationship between lymphoma and chronic renal failure and/or hemodialysis
      was far from clear.

PMID- 9575684
TI  - Pemphigus vegetans involving the esophagus.
AB  - A 44-year-old man with pemphigus vegetans had severe odynophagia. He received an
      endoscopic examination for esophageal involvement. Many white plaque-like lesions
      with an erythematous base were seen on the esophageal mucosa. Biopsy from the
      mucosal epithelial layer showed rounded epidermal cells with large nuclei and
      numerous inflammatory cells including eosinophils.

PMID- 9575685
TI  - Neutrophil eccrine hidradenitis in a patient with AIDS.
AB  - Neutrophilic eccrine hidradenitis (NEH), first described as a rare, transient,
      and benign complication of various chemotherapy regimens for acute leukemia, has
      also been observed in other conditions, including three HIV-positive patients and
      even in otherwise healthy individuals (1-3). A similar histological pattern was
      described after intradermal bleomycin injections into normal human skin (4). We
      report the first case of NEH in a hemophilic HIV infected patient treated with
      stavudine, a new reverse transcriptase inhibitor.

PMID- 9575686
TI  - Four cases of pustulotic arthro-osteitis.
AB  - We describe four cases of pustulotic arthro-osteitis. All of them suffered from
      anterior chest wall symptoms, such as swelling and pain on the sternoclavicular
      joint, sternal angle area, sternocostal joint, and costochondral junction.
      Although chest X-ray findings were all normal, 99mTc-scintigraphy revealed
      increased uptake in the affected areas in all cases. Laboratory examinations
      including rheumatoid factor were negative or normal except for elevation of the
      erythrocyte sedimentation rate and C-reactive protein in 2 cases. After treatment
      with non-steroidal anti-inflammatory drugs and etretinate or topical PUVA, the
      skin lesions on the palms and soles and the arthro-osteitis were moderately
      improved. Pustulotic arthro-osteitis should be considered when a patient with
      pustulosis palmoplantaris complains of anterior chest wall pain and other joint
      pain.

PMID- 9575687
TI  - Subcorneal pustular dermatosis: a follicular variant.

PMID- 9575688
TI  - A case-control study on male hepatocellular carcinoma based on hospital and
      community controls.
AB  - A case control study on male primary hepatocellular carcinoma(HCC) and hepatitis
      B or C virus and some potential risk factors, e.g. blood transfusion, aldehyde
      dehydrogenase 2(ALDH2) genotype and drinking habits, was performed using two
      controls, i.e. a hospital control(HC) and a community control(CC) in Fukuoka and
      Saga Prefectures. Cases were obtained from the Second Department of Internal
      Medicine, Kurume University Hospital. The HCs were obtained from inpatients of
      two general hospitals in Kurume and the CCs were randomly sampled from the Kurume
      citizens being matched with age and sex to each case. Based on the HCs, odds
      ratios(ORs) of developing male HCC were statistically significant due to HBsAg or
      anti-HCV antibody positive status. Some discrepancies were observed between the
      two controls, i.e. higher proportions of past histories of diabetes or
      hypertension, of ALDH2 typical homozygote(ALDH2(1)/ALDH2(1)), and of heavy
      drinkers among the HCs, suggesting slight deviation of the HCs from the CCs in
      alcohol related aspects. Although ORs regarding accumulated amount of alcohol
      intake by age 40 based on the HCs were insignificant, two of the three
      corresponding ORs based on the CCs were statistically significant. Judging from
      alcohol related aspects between the two controls, the ORs for alcohol based on
      the HCs seems to be underestimated.

PMID- 9575689
TI  - Smoking and dietary risk factors for cervical cancer at different age group in
      Japan.
AB  - The importance of the major risk and protective factors for cervical cancer in
      women by age group was evaluated with the use of data from the Hospital-based
      Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. This
      study included 416 cervical cancer cases and 20,985 referents confirmed as free
      of cancer. Cases and referents were divided into three age groups: the younger,
      middle and older age groups (30-44, 45-54 and 55-69 years old, respectively).
      Logistic model was applied separately to the three groups to estimate odds ratios
      (ORs) of smoking, beverage and dietary habits with adjustment for marital and
      reproductive factors. The elevated OR of current smokers was observed
      consistently in all age groups, while alcohol intake did not show any increased
      ORs. Dietary control for health lowered ORs for all three age groups, and the
      effect appeared to be more pronounced among the older age group (OR = 0.49, 95%
      confidence interval: 0.30-0.80). Higher frequency intake of green-yellow
      vegetables consistently afforded lower ORs among all three age groups. This risk
      increment of smoking and risk reduction by dietary control were consistent in all
      age groups. These findings suggested practicable prevention strategy for the
      cervical cancer by modifying general life style.

PMID- 9575690
TI  - A comparative epidemiological study of the effects of regular exercise on health
      level.
AB  - STUDY OBJECT: To reveal the relationship between regular exercise and physical
      fitness, life style, mental health, and other cardiovascular risk factors among
      the Japanese. DESIGN: cross-sectional study. SUBJECTS: Three thousands, one
      hundred and thirty-two individuals (1,795 men and 1,336 women) over 40 years old
      who were examinees at one of seven centers for health promotion. METHODS: A
      questionnaire survey on the life style, a physical fitness tests and clinical
      laboratory tests were performed. RESULTS: Continuing regular exercise was
      associated with high levels of physical strength and their odds ratio (OR) was
      2.09 (95% confidence interval(CI) 1.74-2.50). Many individuals in this group had
      good mental health: the OR for their sensation of fatigue (swift recovery) was
      1.40(95% CI; 1.17-1.68) and that for mood recovery (fast) was 1.44(95% CI; 1.20
      1.72). Thinness and obesity were scarce in this group. CONCLUSIONS: High physical
      fitness level, good mental health, standard body weight are more common in
      regular exercise group.

PMID- 9575691
TI  - The utility of Hayashi's quantification theory type 2 for the rapid assessment of
      the epidemiological survey in the developing countries--in a case of the vaccine
      coverage survey in Yunnan Province, China.
AB  - It is difficult to conduct the epidemiological survey with accurate statistical
      theory in the developing countries due to the problems especially emerged in the
      developing countries such as no availability of the accurate population data,
      limitation of the time for survey, geographical obstacle and financial problems.
      In the consideration of the health needs in those countries, results of the
      epidemiological survey should be reflected in the present health projects as
      rapidly as possible. The authors conducted the survey for the immunization
      coverage of oral poliomyelitis vaccine(OPV) in China by the questionnaire and
      interview. The data was analyzed by using the Hayashi's quantification theory
      type 2 and made clear about the relationship between the health behaviors for
      immunization among residents and several factors. It is considered that this
      theorem can provide the obvious numeral materials about multi-factorial cause
      effect relationship for the decision making and is useful for the rapid
      assessment or initial survey in the developing countries.

PMID- 9575692
TI  - Relationship between exercise and bone mineral density among over 5,000 women
      aged 40 years and above.
AB  - An epidemiological survey was conducted to clarify the relationship between bone
      mineral density(BMD) and exercise at 14 health centers in Ibaraki Prefecture,
      Japan from September 1994 through March 1995. More than 5,000 women participated
      in this survey. Second metacarpal BMD was measured by CXD(Computed X-ray
      Densitometry) method. Information about past history of exercise was obtained by
      questionnaire. sigma GS/D < 2.3(sigma GS/D: a parameter of BMD) was used to
      estimate the suspicion of osteoporosis. Data on 5,124 women aged 40 years and
      above were analyzed. Subjects were categorized into two groups according to the
      presence(n = 1,687) or absence(n = 3,437) of past history of regular exercise.
      sigma GS/D values were significantly (p < or = 0.05) higher in women who have had
      regular exercise in the past than those of the non-exercise group except those
      aged over 70 years. Ball game, foot sports and gymnastics were the main
      exercises. When osteoporosis was suspected based on the measurements of bone
      mineral density, the odds ratio (exercise present/absent) was 0.27 (95%
      confidence limits: 0.08-0.94), 0.82 (0.65-1.04), 0.78 (0.61-0.99), and 1.25 (0.67
      2.35) at 40-49, 50-59, 60-69, and over 70 years, respectively. The results of the
      present study suggest the beneficial influence of exercise on bone mineral
      density and its utility for preventing osteoporosis.

PMID- 9575693
TI  - Epidemiological study of sarin poisoning in Matsumoto City, Japan.
AB  - On the night of June 27, 1994, about 12 liters of sarin were released by
      terrorists in Matsumoto City, Japan. In order to investigate the epidemic,
      community-based questionnaire surveys were conducted. The subjects were all
      inhabitants (2052 people) living and staying in an area of 1050 meters from north
      to south and 850 meters from east to west including the sarin release site.
      Participants included 1743 people who answered the questionnaire at the first
      survey; those with symptoms were contacted for follow-up at four months and one
      year after the episode. The number of sarin victims were 471 persons. Muscarinic
      signs were common to all victims; nicotinic signs were only seen in severely
      affected victims. The geographical distribution of sarin victims was closely
      related to the direction of the wind. Three weeks after the intoxication, 129
      victims still had some symptoms such as dysesthesia of the extremities. At that
      time, many victims had begun to experience asthenopia, which was even more
      frequent at four months. Although victims who felt sarin-related symptoms had
      decreased by a year, some still had symptoms such as asthenopia. Sarin released
      in a suburban area affected approximately 500 inhabitants living nearby; some
      still had symptoms a year after the intoxication.

PMID- 9575694
TI  - Associations of individuals' health-related behavior with their own or their
      spouses' smoking status.
AB  - BACKGROUND: Many studies indicated that smokers have poor health habits such as
      high alcohol consumption and imbalanced nutrient intakes. These habits could
      affect the health-related behavior of smokers' families. METHODS: To investigate
      the relationship between an individual's health-related behavior (nutrient
      intakes and participation in cancer screening) and their spouses' smoking status,
      we analyzed data collected using a self-administered questionnaire during a
      cohort study. We compared nutrient intakes and cancer screening participation
      rates between subjects grouped according to their spouses' smoking status, using
      a multivariate linear regression model to adjust for each subject's age and
      alcohol consumption. RESULTS: There was an association between husbands' and
      wives' smoking status (never and current only). Poor micronutrient intakes and
      cancer screening participation rates were associated with both the subjects' and
      their spouses' smoking habits. This tendency was most apparent among male smokers
      and nonsmoking women. However, among nonsmoking men and female smokers, there
      were no statistically significant differences between groups classified according
      to their spouses' smoking status. CONCLUSION: Spouses' smoking habits were
      associated with poor health-related behavior in their partners.

PMID- 9575695
TI  - A retrospective cohort study on retirement and mortality for male employees of a
      local government of Japan.
AB  - This retrospective cohort study describes the mortality pattern after retirement
      and examines associations of the last job position and work status immediately
      after retirement with the mortality for male employees who retired from Kochi
      prefectural government. The subjects include 514 retirees over the 1977-1981
      period, who were followed for 9.8 years after retirement, and 721 retirees over
      the 1982-1986 period, who were followed for 5.8-9.8 years. All subjects were
      hypothesized to have retired at a normal retirement age. Mortality risk was
      stable through the follow-up period subdivided into two-year intervals in both
      cohorts of retirees. In both cohorts, men who did not work immediately after
      retirement had increased mortality within the first two years of retirement
      compared with those who worked immediately after retirement. This finding is
      consistent with the mortality pattern explained by health related selection into
      working after retirement. The present study does not show a meaningful mortality
      fluctuation over the post-retirement period among male employees of the local
      government. Lack of information on ages and health status at retirement of
      individual subjects hampers discussion about causality of observed associations
      between two study variables concerning pre- and post-retirement characteristics
      and post-retirement mortality.

PMID- 9575696
TI  - Descriptive epidemiology of pancreatic cancer in Japan.
AB  - This paper aimed to explore descriptive epidemiological features of pancreatic
      cancer in Japan, by examining secular trends in mortality (1950-1995) and
      incidence rates (1975-1991), and also to discuss background factors possibly
      ascribable to the recent variation in mortality and incidence rates. The age
      adjusted mortality rate (adjusted by the 1985 model population) has increased by
      approximately 9-fold in both males (from 1.4 to 12.5 per 100,000 population) and
      females (from 0.8 to 6.8 per 100,000 population) between 1950 and 1995. But it
      began to level off in both sexes since 1985. The age-adjusted incidence rate has
      remained plateau in both sexes, but likely showed a downward trend since 1988 in
      females. The older age groups showed the most steep increasing gradient in both
      age-specific mortality and incidence rates in both sexes, whereas a little or no
      apparent increase was observed in young age groups. Diagnostic improvement and
      increased cigarette consumption were believed to be the two major factors
      contributing to the increased mortality and incidence rates in Japan, but further
      epidemiological studies will be required to clarify possible background factors
      for the recent levelling-off of the mortality and incidence rates.

PMID- 9575697
TI  - The estimation of cancer incidence in Aichi Prefecture, Japan: use of degree of
      completeness of registration.
AB  - This study was conducted to estimate true incidence of the total number of cancer
      cases and of cancers at selected sites in the population of Aichi Prefecture,
      Japan, using the degree of completeness of registration (CR). Information on
      incidence (I), death (D), and cases first notified via death certificate (DCN)
      was based on the data from 1976 to 1993. Using this information, CR for each
      cancer site was calculated by gender and a 3-year period of diagnosis [CR = (1
      PDCN l/D)/(1-PDCN), PDCN: proportion of DCN cases]. The true number of incident
      cases and incidence rates (estimated incidence rate: EIR) were then estimated
      from the number of cases observed and from CR. CR for all sites of cancer was 62
      78 percent in males and 54-72 percent in females, and CR was higher in cancers
      with low I/D ratios than those with high I/D ratios. Annually, about 2,500-3,000
      cases in each gender were unreported. The EIR of all sites was estimated at 252
      280 in males and 213-207 in females compared with the incidence rates observed
      (observed incidence rate: OIR) as 157.0-218.6 in males and 115.3-149.2 in
      females. OIR was closer to the EIR for cancers with low I/D ratios than those
      with high I/D ratios. These values are important for planning and evaluating
      cancer control strategies in the population.

PMID- 9575698
TI  - Mortality in relation to the type of household among elderly people living in a
      community.
AB  - The objective of this study was to determine whether there is an association of
      mortality with the type of household in elderly people. A cohort of 1,352 elderly
      people aged 65 years and over at baseline in October 1992 was followed for 42
      months. Follow-up was completed for 1,266 (93.6%) (172 deceased and 1,094 alive).
      From the analysis using the Kaplan-Meier method and the log-rank test, male sex,
      older age group (75 years and over), no satisfaction with present dwelling,
      disability, no use of health checks, no practices of daily preventive health
      promotion, no participation in social activities, and no finding life worth
      living (no Ikigai) were univariately statistically significantly related to
      mortality. Furthermore, elderly people living with their spouse only or living
      alone had higher survival rates than those living with their spouse and children
      or living with their children, and the curves among the four subclasses of
      household were significantly different. From the Cox proportional hazards model,
      living with a spouse only remained as an independent predictor for survival, and
      living alone was not an increased risk factor for mortality, controlling for sex,
      age, housing conditions, disability, use of health management, and psychosocial
      conditions.

PMID- 9575699
TI  - Prevalence of Helicobacter pylori infection in Bangladeshi population.

PMID- 9575700
TI  - Howard Waitzkin: intellectual for the disadvantaged.

PMID- 9575701
TI  - Is our work dangerous? Should it be?
AB  - Three case histories show how work in the medical social sciences--to the extent
      that such work reveals the origins of health problems in social structures of
      wealth and power--can become dangerous enough to threaten one's livelihood and in
      some instances one's very life. In this presentation, I encourage critical and
      engaged scholarship by referring to examples of dangerous work that should
      receive more attention: social medicine in Latin America and the critique of
      managerial ideology in the United States. Although social medicine has become a
      widely respected field of research, teaching, and clinical practice in Latin
      America, its accomplishments remain little known in the English-speaking world.
      For centuries, indigenous cultures in Latin America have held belief systems
      linking social conditions to patterns of illness and death. Latin American
      accounts of social medicine's history emphasize its European origins, especially
      in the contributions of Rudolf Virchow. In the United States, with the impact of
      the Flexner Report (1910) and its supporters, Virchow's vision of social medicine
      went into decline. On the other hand, in Latin America, social medicine
      flourished as a focus of education and research. Since social medicine's "golden
      age" during the 1930s, teachers, researchers, and practitioners have produced
      major achievements despite the dangers of this work, which in several instances
      have included torture, imprisonment, or death. An ideology favoring managerial
      decision making in the United States has influenced crucial policy decisions, and
      the justifications for these decisions have manifested symbolic politics in
      addition to the evaluation of factual evidence. With ambiguous empirical support,
      managerial ideology has fostered the general growth of managed care, the
      implementation of Medicaid managed care by state governments, the expansion of
      managed care in rural areas, and the impact of "evidence-based medicine" on
      policy and clinical decisions. If the occupational risks of critical work in the
      medical social sciences are not taken, we forfeit some of the most important
      gifts offered by "the sociological imagination."

PMID- 9575702
TI  - Community-level socioeconomic status effects on adult health.
AB  - Do the socioeconomic characteristics of a community affect one's health? This
      research examines whether the socioeconomic characteristics of communities are
      associated with the health of community residents, over and above the socio
      economic characteristics of individual residents and their families. This is the
      first study to examine the independent associations between community-level socio
      economic status (SES) and individual-level health using a nationally
      representative sample of adults in the United States. Results indicate that a
      person's health is associated with SES characteristics of the community over and
      above one's own income, education, and assets. However, individual-level and
      family-level SES indicators are stronger predictors of health than community
      level SES indicators. This research suggests that improving individual-level and
      family-level socioeconomic circumstances may be the more direct way to improve
      the health of individuals, but that understanding the community context in which
      a person lives may also ultimately be important to improving health.

PMID- 9575703
TI  - Assessing sex differences in vulnerability among employed parents: the importance
      of marital status.
AB  - Despite earlier claims that women are generally more vulnerable than men to
      stressors, recent research on mental health indicates that sex differences in
      vulnerability are highly specific and depend on the type of stressor and disorder
      considered. My paper extends previous work on this topic by suggesting that
      gender variation in stress-reactivity is also contingent upon people's marital
      status. To illustrate the importance of marital status for differential
      vulnerability, my study assesses sex differences in the impact of work and family
      role strains on depression and alcohol use-abuse among married and unmarried
      employed parents who participated in the second wave of the National Survey of
      Households and Families (N = 2937). My analyses indicate that mothers generally
      are not more vulnerable than fathers, but that sex differences in parents'
      response to stress depend on the type of stressor and disorder involved. My
      analyses also reveal significant marital status contingencies in the effects of
      stress on mothers' compared to fathers' symptoms of distress. Finally, although
      married and unmarried mothers do not differ in their response to work or family
      stress, my analyses show that parental strain is more harmful to unmarried than
      married fathers. Overall, my research identifies an important, though previously
      overlooked, factor influencing sex differences in vulnerability and further
      specifies the types of stressors which are etiologically important for married
      and unmarried mothers and fathers. I interpret findings from the contextual
      approach to differential vulnerability, arguing that the circumstances in which
      stressors occur influence their meaning, emotional significance, and
      psychological impact.

PMID- 9575704
TI  - The quality of adolescent friendships: long-term effects?
AB  - While differing in etiological emphasis, a variety of theoretical perspectives
      seem to coalesce around the notion that youthful friendships are "good" for
      development. Sociometric studies have documented that low status youth are at
      risk for a variety of negative outcomes, but there has been little longitudinal
      research focused on the qualities of youths' relations with peers. We conducted
      interviews focusing on adolescents' relations with their friends with 942
      adolescents in 1982. In 1992, follow-up interviews (N = 620) allowed us to
      determine whether level of intimacy with friends was associated with a range of
      adult outcomes, once sociodemographic characteristics and level of family
      intimacy were taken into account. Adolescents who reported greater levels of
      intimacy with friends do not, as adults, indicate that they have significantly
      higher self-esteem, better relations with their parents, or increased marital
      satisfaction. In addition, the level of intimacy is not related to adult reports
      of psychological distress, involvement in criminal activity, or use of violence
      against one's spouse. In contrast, sociodemographic characteristics and level of
      attachment to parents are related to many of these kinds of outcomes. We also
      discuss implications for attachment or relational perspectives on youthful
      friendship.

PMID- 9575706
TI  - On hope: a recollection.

PMID- 9575705
TI  - The long arm of the farm: how an occupation structures exposure and vulnerability
      to stressors across role domains.
AB  - We examine how the occupation of farming structures the stress experiences of
      individuals through the timing and placement of actions. Further, we show how
      occupations have effects that spillover into family and friendship relationships.
      We find that farming affects both exposure and vulnerability to stressors.
      Specifically, farm men are more exposed to financial and job-related stressors,
      while less prone to marital conflict, than non-farmers. Given the importance of
      cohesion in farm family operations, farm men are more vulnerable to such conflict
      when it occurs. However, farm men are unaffected, if not consoled, by knowledge
      of undesirable events in the lives of their friends. We explore this finding and
      conclude that farm men use downward social comparisons to cope with the high
      levels of uncertainty characteristic of farming in the aftermath of the 1980s
      farm crisis.

PMID- 9575707
TI  - A good death.

PMID- 9575708
TI  - Striving for balance: palliative care patients' experiences of making everyday
      choices.
AB  - A fundamental principle of palliative care is the provision of patient-centred
      care, an approach explicitly based on the patient's perspective. Although much
      attention has been given to determining patients' preferences for involvement in
      medical decisions, choices related to personal and nursing care routines have
      been largely ignored in the literature. Data from participant observations of
      nurse-patient interactions involving 16 palliative care patients and their nurses
      as well as 10 in-depth open-ended interviews with patients were analyzed using
      grounded theory methods. Although the choices made by patients appeared
      uncomplicated on the surface, the context of unfamiliarity, uncertainty, and
      unpredictability in palliative care increased the underlying complexity of
      decision making. Through a process of deliberation and trade-offs, patients
      attempted to regain or maintain some balance in their lives. This process of
      striving for balance consisted of three overlapping phases: weighing things up,
      communicating choice, and living with one's choices.

PMID- 9575709
TI  - Assessment and management of medically ill patients who refuse life-prolonging
      treatments: two case reports and proposed guidelines. Capital Health Authority
      Regional Palliative Care Program.
AB  - Patients who have chosen to have treatment withdrawn because of debilitating
      conditions pose a special problem for palliative care. We report on two such
      patients: patient 1 refused amputation of a gangrenous leg and patient 2 refused
      food and hydration after a series of strokes. The management of these patients
      through the dying process is discussed and guidelines are suggested. The criteria
      for competency include both a general cognitive and psychiatric assessment as
      well as a specific evaluation of the patient's ability to make the treatment
      withdrawal decision. Treatable symptoms which impair the patient's quality of
      life and have an impact on the decision should be corrected. If a proxy decides
      to withdraw therapy in an incompetent patient, this decision should accord with
      the patient's known wishes and values as far as possible. The beneficence of the
      decision may be assessed according to the disease process, degree of suffering,
      and risks of accepting treatment. The complexity of these cases calls for a
      multidisciplinary approach, and the palliative care team should work in
      collaboration with the primary care treatment team.

PMID- 9575710
TI  - Capacity to choose place of residence: autonomy vs beneficence?
AB  - Health care workers often perceive a conflict between autonomy and beneficence
      when dealing with clients living at risk in the community. Respect for personal
      freedom and the desire to help and protect vulnerable people frequently appear to
      demand opposite interventions. The assessment of decision-making capacity is a
      vital part of any process that deals with these complicated situations and can
      resolve some of the apparent conflict. Standardized assessment tools which are
      flexible enough to deal with the complexities of capacity assessment are needed.
      Health care workers aim to maximize the safety of people incapable of making
      decisions while protecting the freedom and autonomy of the capable. Some limits
      to autonomy must be accepted, especially where others' interests are threatened.

PMID- 9575711
TI  - Community physicians describe management issues for patients expected to live
      less than twelve months.
AB  - We examine management issues experienced by community physicians providing care
      to patients they expect to die within a year. In a case series, 61 physicians in
      northern New England enrolled 182 consecutive dying patients. Important
      management issues for these patients were recorded at enrollment and eight months
      later. The patients' average age was 74 years; most had cancer (48%) or
      cardiovascular disease (38%). Almost two-thirds of the patients died within eight
      months of enrollment. Major management issues for the physicians in care of these
      patients were deficits in basic self-care, emotional support, pain control, and
      nutrition. Pain control and family need for support were reported most
      frequently. Although demand for physician time was seldom a major management
      issue, when it occurred it correlated with patients' emotional needs or their
      desire to extend life (p < 0.01). Two barriers to optimum care commonly cited by
      physicians were (a) the differences in treatment expectations between family
      members, patients, and physicians and (b) the incurable, progressive nature of
      the patients' diseases. Efforts to improve care for patients who have limited
      life expectancy should further explore the perceptions of community physicians.

PMID- 9575712
TI  - On the nature of hope in palliative care.

PMID- 9575713
TI  - Is there hope, doctor?

PMID- 9575714
TI  - Reflections on breathing the same air.

PMID- 9575715
TI  - Use of sedation by a hospital palliative care support team.

PMID- 9575716
TI  - World Health Organization. Guidelines for counselling people about Human
      Immunodeficiency Virus.

PMID- 9575717
TI  - All bull and proud of it.

PMID- 9575719
TI  - Clinicopathological images. Gastric polyps.

PMID- 9575718
TI  - Intracytoplasmic sperm injection into oocytes of severe male infertility
      patients: UAMS experience. University of Arkansas for Medical Sciences.

PMID- 9575721
TI  - Tuberculous pericarditis?

PMID- 9575722
TI  - Risk factor profile: men who have sex with men.
AB  - From 1983 through January 12 of this year, the cumulative number of HIV-positive
      persons reported is 3,919. Of that number, 2,369 meet AIDS case definition. For
      the 30-day period ending January 12, 27 new cases of HIV and 16 new cases of AIDS
      were reported. Of the 2,369 AIDS cases reported since 1983, 1,200 (51%) are
      living and 1,169 (49%) are decreased.

PMID- 9575723
TI  - Radiological case of the month. Epiploic appendagitis.

PMID- 9575724
TI  - [Metabolism of purine compounds in psoriasis].
AB  - The pool of free purine derivatives and activities of the key enzymes of purine
      metabolism (adenosine deaminase, purine nucleoside phosphorylase, and 5'
      nucleotidase) in lymphocytes, erythrocytes, and epidermis homogenates were
      measured in 20 normal subjects and 15 patients with psoriasis by high-performance
      liquid chromatography. The levels of AMP, GMP, and IMP purine monophosphates are
      decreased in the epidermis and red cells of psoriasis patients, whereas the final
      products of hypoxanthine, xanthine, and uric acid metabolism are accumulating,
      and the activities of ADA and PNP are increased double in the skin, all this
      indicating purine derivatives catabolism.

PMID- 9575725
TI  - [A simple method of studying oxidation resistance of heparin-precipitated blood
      beta lipoproteins].
AB  - Decrease of beta-lipoprotein resistance to copper-dependent oxidation is an
      important diagnostic criterion of risk of atherosclerosis. We developed a simple
      method for assessing resistance of heparin-precipitated beta-lipoproteins to
      oxidation induced by 50 microM copper ions. A strong positive correlation between
      the oxidation of precipitated and ultracentrifuged beta-lipoproteins in the
      presence of 50 and 10 microM copper ions, respectively, was revealed. In coronary
      patients oxidation resistance of precipitated beta-lipoproteins was decreased in
      comparison with that in healthy donors. The method is simple, informative, and
      easily available for clinical biochemical laboratories.

PMID- 9575726
TI  - [Forms of hemostasis disorders in the postoperative period].

PMID- 9575727
TI  - [Determination of the activity of Willebrand's factor by laser analyzer of
      platelet aggregation].
AB  - A modification of von Willebrand' factor/ristocetin cofactor activity test is
      proposed. Agglutination of formalin-treated platelets is monitored in the
      aggregation analyzer from changes in the light transmission in the specimen. The
      test is sensitive and reproducible. It is intended for clinical laboratories to
      be used in patients with hematological diseases and the endotheliopathy syndrome
      of different etiology.

PMID- 9575728
TI  - [Beta-thalassemia and Hb D in patients with anemia].
AB  - Twelve patients with anemias and their close relatives were examined: 8 adults (3
      men and 5 women) and 4 children (3 boys and 1 girl). Six of them were Armenians,
      1 woman was Russian, and the rest were of mixed origin: 3 Russian-Azerbaijan
      Ukrainian, 1 child Russian-Ukrainian-African, and 1 woman Russian-Ukrainian.
      Hemoglobinopathies were detected in 10 subjects from 4 families (3 families from
      Donetsk and 1 from Moscow). Homozygotic beta-thalassemia major (Hb F 98.9%) was
      diagnosed in a 2-year-old Armenian girl from Donetsk. The girl lags behind in
      development and suffers from anemia with hepatosplenomegaly and jaundice.
      Heterozygotic beta-thalassemia minor with increased levels of Hb A2 and Hb F was
      diagnosed in her parents (Armenians from Azerbaijan). A 15-year-old Russian
      Azerbaijan-Ukrainian boy from another family in Donetsk had beta-thalassemia with
      HbD (94%). The boy suffers from anemia with hepatosplenomegaly, jaundice, and
      chronic hepatitis. Heterozygotic beta-thalassemia with increased levels of Hb A2
      and Hb F was revealed in proband's mother and brother; the father was not
      examined. alpha-Thalassemia is suspected in a 3-year-old boy from a Russian
      Ukrainian-African family in Donetsk; he presented with a very small "fast"
      abnormal hemoglobin fraction. The boy suffers from anemia with splenomegaly and
      systolic murmur. Blurred form of thalassemia minor is diagnosed in the mother.
      The father, an African from Zaire, was not examined. Heterozygotic beta
      thalassemia with increased Hb A2 level was revealed in a 20-year-old Armenian boy
      from Moscow. He presented with manifest splenomegaly, chronic gastritis, and
      mitral valve prolapse. His mother suffers from thalassemia minor, was anemic
      during pregnancy, and there are cases of anemia in the family. No hematologic
      disorders were found in the father. No hemoglobinopathies were detected in a 59
      year-old Russian women from the town of Tver with very grave anemia; apparently,
      her condition was acquired, but not hereditary. Data on patients in the city of
      Donetsk are of special interest, for there are virtually no reports about
      hemoglobinopathies in the Ukraine.

PMID- 9575729
TI  - [New methods of assessing intoxication and blood cell response in patients with
      infectious toxicoses].
AB  - The microviscosity indexes of cell membranes of erythrocytes, neutrophils, and
      lymphocytes were estimated in children with acute respiratory diseases with and
      without infectious toxicosis. The erythrocyte microviscosity most completely
      reflects the degree of toxicosis. The ratio of membrane microviscosity indexes of
      neutrophils to that of lymphocytes demonstrates the specific response of blood
      cells to infectious toxic exposure.

PMID- 9575730
TI  - [Clinical pharmacokinetics: the basis of laboratory monitoring of drugs
      (lecture)].

PMID- 9575731
TI  - [Tasks and possibilities of bacteriological laboratories in computer-assisted
      control of hospital infections].
AB  - The authors discuss the organization of epidemiological surveillance of hospital
      infections, carried out by bacteriological laboratories. The principal tasks of
      epidemiological surveillance of pyoseptic infections in surgical hospitals are
      formulated. The potentialities of using the data of computer monitoring of
      nosocomial infections are discussed. This method helps adopt epidemiologically
      justified decisions.

PMID- 9575732
TI  - [Method of quantitative determination of staphylococcal hyaluronidase activity].
AB  - The proposed method for measuring hyaluronidase activity of microorganism is
      based on prevention of hyaluronic acid clot formation with rivanol under the
      effect of hyaluronidase. This made possible the quantitative and qualitative
      detection of hyaluronidase activities of different staphylococcus species and
      strains. The maximum level of the enzyme and highest rate of its detection were
      typical of St. aureus. Its strains producing hyaluronidase in quantities of at
      least 0.5 IU are significantly (p < 0.01) more often isolated from medical staff.

PMID- 9575733
TI  - [Study of antibiotic sensitivity of microorganisms by the method of diffusion in
      agar layers].
AB  - The proposed method for assessing microorganism sensitivity in solid and
      semisolid liquid nutrient media provides more accurate results and permits
      isolation of resistant forms of bacteria and studies of antibiotic interactions.
      Bacteriological study of latent growth zones of bacteria, although rather long,
      makes the results more reliable. The method can be used for assessing the
      microflora sensitivity in patients without resorting to isolation of pure
      cultures and in biotechnology for isolation of new antibiotics.

PMID- 9575734
TI  - [Method of collecting duodenal bile specimens for determination of lipid
      contents].

PMID- 9575735
TI  - [Clearance characteristics of carbon hemosorbents].

PMID- 9575736
TI  - [Assessment of DNA and RNA synthesis in T- and B-lymphocytes].

PMID- 9575737
TI  - [Improved method of preparing neuroendocrine and endocrine tissue samples for
      radiometry].

PMID- 9575738
TI  - [Nutrition and healthy life style in prevention and treatment of osteoporosis].

PMID- 9575739
TI  - [DIC syndrome in clinical medicine].

PMID- 9575740
TI  - [Melatonin production in patients with duodenal ulcer at different stages of
      disease].
AB  - Melatonin secretion was measured in patients with duodenal ulcer in exacerbation
      and remission. Melatonin production was found abnormal both in duodenal ulcer
      remission and exacerbation. It is suggested that melatonin may participate in
      pathogenesis of duodenal ulcer.

PMID- 9575741
TI  - [Pneumonia in young males in extreme conditions].

PMID- 9575742
TI  - [Clinico-diagnostic role of ferritin and lactoferrin assays in benign and
      malignant affections of lungs and pleura].
AB  - Immunochemical tests of blood sera from 160 healthy residents of the town of
      Astrakhan were performed to determine standard quantities of ferritin and
      lactoferrin in the serum. Examinations of the saliva from 280 healthy subjects
      provided the frequency of occurrence and levels of excretory lactoferrin. These
      iron-containing proteins were also assessed in different biosubstrates (blood
      serum, sputum, saliva, pleural fluid, lung tissues) from 550 patients with benign
      and malignant lesions of the lungs and pleura. Tests for ferritin and lactoferrin
      proved useful in evaluation of bronchopulmonary inflammation activity, early
      detection of pulmonary and intrapleural supputation, differential diagnosis of
      chronic nonspecific pulmonary diseases and lung cancer. The excretory salivary
      lactoferrin provided sufficient information on the condition of adaptive
      mechanisms of local defense of the lungs in premorbid state in 420 workers of the
      gas-processing plant exposed to aggressive occupational pollutants.

PMID- 9575743
TI  - [Prevention of ischemic stroke and conception of hemodynamic reserve].
AB  - Central and cerebral hemodynamics was studied using echocardiography and
      transcranial dopplerography in 200 poststroke patients over 60 in the course of 5
      year follow-up. It was established that cardiac hypodynamic syndrome, i.e.
      continuous or paroxysmal fall of minute blood volume below 3 l, is the most
      significant contributing factor in the onset of cerebral ischemia. Drugs are
      recommended for prevention of ischemic stroke. Those lowering cardiac hemodynamic
      reserve should be excluded in patients at high risk of acute failure of cerebral
      circulation.

PMID- 9575744
TI  - [Impulse barotraining in the regimen of daily atmospheric pressure fluctuation as
      a method of body resistance stimulation after aortocoronary bypass surgery].

PMID- 9575745
TI  - [Role of geomagnetic field in development of biorhythm profile of ventricular
      arrhythmia onset].
AB  - To clarify the role of geomagnetic field (GMF) on development of circadian
      profile of life-threatening ventricular tachycardia 13 children aged 9-14 years
      underwent 24-h Holter monitoring (Oxford Medilog Optima, Great Britain). 8
      children had Romano-Ward syndrome, catecholaminergic bidirectional ventricular
      tachycardia (group 1), 5 children had sick sinus syndrome (group 2). In patients
      from group 1 "torsade de pointes", episodes of polymorphic bidirectional and
      monomorphic ventricular tachycardia, frequent ventricular extrasystole were
      recorded in 1, 5 and 2 patients, respectively. Patients of group 2 had asystole
      up to 5 seconds. Circadian pattern of arrhythmia and heart rate variability BPC
      (mean, SDNN, SDAN-N-i, SDNN-i, rMSSD, pNN50) were compared to 3-hour values of
      Ap(Ar)-index of geomagnetic activity in the examination day in Moscow with
      estimation of the correlation coefficient (r). Changes in GMF were not correlated
      with BPC in group 1 children. Frequency of arrhythmia and Ap-index were related
      in 5 of 8 children in group 1: r from +0.67 (p < 0.05) to +0.97 (p < 0.01). 2
      children from group 1 had no correlation between frequency of tachyarrhythmia and
      dynamics of GMF but demonstrated relation between frequency of arrhythmia and
      mean value of RR interval (Mean): r-0.73 (p < 0.05) and 0.71 (p < 0.05). Patients
      of group 2 exhibited no significant correlation between the frequency and
      duration of rhythmic pauses and GMF changes. This may be due to strong dependence
      of bradyarrhythmia circadian profile on endogenic circadian endocrine rhythms of
      parasympathetic regulation. The conclusion was made on possible effect of GMF on
      provocation and formation of circadian profile of life-threatening ventricular
      tachyarrhythmia in children and adolescents. Sympathetic activation may
      participate in realization of this effect.

PMID- 9575746
TI  - [Antibodies to beta2-glycoprotein I in systemic lupus erythematosus: new
      laboratory marker of antiphospholipid syndrome].
AB  - Antibodies to beta 2-glycoprotein in the serum of patients with antiphospholipid
      syndrome (APS) were found by many investigators, but their results appeared
      contraversional. We studied clinical significance of antibodies to beta 2
      glycoprotein I (anti-beta 2-GPI) in patients with SLE. 69 patients with verified
      SLE were examined for lupus anticoagulant (LA), antibodies to cardiolipin (aCL)
      and anti-beta 2-GPI. 44(65%), 46(67%), 49(71%), 19(28%), 16(23%) patients were
      positive for LA, IgG-aCL, IgM-aCL, IgG-anti-beta 2-GPI and IgM-anti-beta 2-GPI,
      respectively. Hyperproduction of IgG-anti-beta 2-GPI correlated with APS
      development as a whole, its separate clinical symptoms (venous and arterial
      thromboembolism, obstetric pathology and thrombocytopenia) and some comcomitant
      clinical signs (trophic crural ulcer, hemolytic anemia, valvular heart
      disorders). Moreover, an increase in concentration of IgM-anti-beta 2-GPI was
      associated with habitual abortion. Both isotypes of anti-beta 2-GPI occurred more
      frequently in the sera positive by LA and aCL. It is interesting that we
      discovered IgG-anti-beta 2-GPI more often in early than late postthrombolytic
      period. Thus, anti-2b2-GPI is a new serological marker of APS. Its detection is
      clinically important for upgrading diagnosis of APS.

PMID- 9575749
TI  - [Distinguishing features of infectious endocarditis in geriatric practice].

PMID- 9575747
TI  - [Comparative efficacy of and tolerance to prestarium and lomir in long-term
      treatment of hypertensive subjects].
AB  - An antihypertensive action and tolerance of prestarium and lomir were studied in
      31 and 33 hypertensive patients, respectively. They had hypertension stage I-II
      and took the drug for 12 months. Monotherapy with prestarium in a dose 8 mg/day
      and lomir (10 mg/day) given twice a day provides a complete hypotensive effect
      for a year in 56 and 62% of patients, respectively. Combinations prestarium +
      ariphon, lomir + anapriline or verapamil increased the above number to 100%. The
      occurrence of side effects of long-term lomir monotherapy was 4 times higher than
      due to prestarium therapy (39.4 versus 9.7%, respectively).

PMID- 9575750
TI  - [Factors underlying gastroduodenal pathology in children].
AB  - Correlation analysis conducted in 106 children with chronic gastroduodenitis
      enabled us to distinguish leading factors in the onset of this disease, to
      estimate the strength of connection between clinicoanamnestic and laboratory
      instrumental methods of investigation. A strong correlation was found in children
      with gastroduodenitis between changes of sialo-containing compounds, secretory
      IgA in the saliva and inflammation severity.

PMID- 9575751
TI  - [Bronchopulmonary syndrome in differential diagnosis of infectious diseases].

PMID- 9575752
TI  - [Terminological problems in cardiology and other fields of medicine].

PMID- 9575753
TI  - [Is it valid for clinicians to reject functional pathology?].

PMID- 9575755
TI  - [Role of I.A. Kassirskii in development of clinical medicine (on the 100th
      anniversary of his birth)].

PMID- 9575756
TI  - [Herman Burgave: the twilight of teaching clinical medicine in Leiden
      university].

PMID- 9575757
TI  - [Calendar of historical events in the history of medicine in 1998].

PMID- 9575759
TI  - Utilization of combat stress control detachments.

PMID- 9575760
TI  - A generic drug primer: regulatory aspects and scientific concepts.
AB  - The regulatory aspects of generic drug substitution and the scientific concepts
      that serve as the basis for generic drug approval are discussed, with emphasis on
      the source of therapeutic equivalence information compiled by the Food and Drug
      Administration in Approved Drug Products with Therapeutic Equivalence
      Evaluations. The Food and Drug Administration's determination of bioequivalence
      for immediate-release and extended-release dosage forms is summarized, with a
      discussion of the underlying assumptions and current issues regarding
      bioequivalence testing. Medical practitioners must comply with the regulations
      stated in each state's Pharmacy Practice Act when allowing generic substitution
      and should ensure that the substituted product is therapeutically equivalent to
      the prescribed product.

PMID- 9575761
TI  - Biological warfare training: infectious disease outbreak differentiation
      criteria.
AB  - The threat of biological terrorism and warfare may increase as the availability
      of weaponizable agents increases, the relative production costs of these agents
      decrease, and, most importantly, there exist terrorist groups willing to use
      them. Therefore, an important consideration during the current period of
      heightened surveillance for emerging infectious diseases is the ability to
      differentiate between natural and intentional outbreaks. Certain attributes of a
      disease outbreak, although perhaps not pathognomonic for a biological attack when
      considered singly, may combine to provide convincing evidence of intentional
      causation. These potentially differentiating criteria include proportion of
      combatants at risk, temporal patterns of illness onset, number of cases, clinical
      presentation, strain/variant, economic impact, geographic location,
      morbidity/mortality, antimicrobial resistance patterns, seasonal distribution,
      zoonotic potential, residual infectivity/toxicity, prevention/therapeutic
      potential, route of exposure, weather/climate conditions, incubation period, and
      concurrence with belligerent activities of potential adversaries.

PMID- 9575762
TI  - Multidisciplinary treatment of persistent symptoms after Gulf War service.
AB  - Research suggests that individuals commonly describe persistent symptoms or
      syndromes after a war. After the Persian Gulf War, the Department of Veterans
      Affairs and the Department of Defense initiated registries and expedited health
      care for those with Gulf War-related health concerns. At Walter Reed Army Medical
      Center, the Gulf War Health Center was created in mid-1994 to contribute a
      continuum of care for those with Gulf War-related health problems. The purpose of
      this report is to describe the Gulf War Health Center's Specialized Care Program,
      a 3-week intensive outpatient multidisciplinary treatment program for people with
      persistent, disabling Gulf War-related symptoms. The program uses an evidence
      based model of multidisciplinary care employed at chronic pain centers
      internationally and shown to yield stable improvements in pain, mood, health care
      use, and return to work rates. A patient is described to illustrate how the
      program works. Finally, a Deployment Medicine Treatment Center is proposed, a
      multidisciplinary treatment center like the Specialized Care Program that would
      offer care to those with persistent, disabling symptoms after all future
      deployments.

PMID- 9575763
TI  - Prevalence of premilitary adult sexual victimization and aggression in a Navy
      recruit sample.
AB  - U.S. Navy recruits (n = 3,776) were surveyed for premilitary histories of adult
      sexual assault. They completed a survey designed to estimate rates for
      experiences as victims (women) and perpetrators (men) of attempted and completed
      rape since the age of 14. The results show that 45.5% of the women reported being
      the victim of attempted (9.4%) or completed rape (36.1%) before entering the
      Navy. Male recruits' self-reports indicated that 14.8% admitted perpetrating
      attempted (3.5%) or completed rape (11.3%) before entering the Navy. A high
      percentage of recruits in this study reported histories of sexual assault. Female
      victims of sexual assault are at high risk of incurring somatic and/or
      psychological problems that require treatment by health care professionals. Male
      perpetrators of sexual assault are at high risk of repeating their behavior. The
      results of this study suggest that it may be cost-effective to develop treatment
      education, and prevention programs for military recruits.

PMID- 9575765
TI  - Economic consequences of tobacco use for the Department of Defense, 1995.
AB  - This study used Centers for Disease Control and Prevention methodology to analyze
      the costs of smoking-attributable mortality and morbidity within the Department
      of Defense (DoD) based on health care costs, characteristics of the beneficiary
      population, and disease characteristics. Direct health care costs attributed to
      smoking were estimated at $584 million. Smoking-attributable disease accounted
      for 16% of the deaths as well as approximately 10% of all hospital bed days and
      1.5% of all active duty hospitalizations. Lost productivity among active duty
      personnel for hospitalization and smoke breaks was valued at $346 million. A
      significant portion of DoD health care resources is spent caring for smoking
      attributable disease, which is preventable. This report reinforces the benefits
      possible from the new emphasis on wellness promotion within the DoD. Efforts are
      needed to prevent the initiation of smoking and encourage smoking cessation in
      order to reduce health care costs and increase the probability for long and
      healthy lives for DoD beneficiaries.

PMID- 9575764
TI  - Prevalence and timing of sexual assaults in a sample of male and female U.S. Army
      soldiers.
AB  - OBJECTIVE: This study was designed to assess the prevalence and timing of sexual
      assault experiences in a sample of U.S. Army soldiers. METHODS: Self-administered
      surveys were completed by 555 male and 573 female soldiers in combat service and
      combat service support units. RESULTS: One-fifth of the women reported a
      completed rape (22.6%), and 50.9% of women and 6.7% of men reported any sexual
      assault. The majority of sexual assaults occurred before the soldiers entered the
      military, and 25% of women and 1% of men reported an attempted or completed rape
      during childhood. Sexual assault history also varied by sociodemographic
      characteristics. CONCLUSION: Results suggest that a history of childhood sexual
      abuse may be more widespread among female soldiers than among civilian women, and
      that ascribed and achieved status characteristics may differentially expose
      soldiers to sexual assaults both before and after they enter the military. Health
      care assessments should include details of a soldier's sexual assault history.

PMID- 9575766
TI  - Psychosocial factors associated with smoking in Air Force recruits.
AB  - The ability to identify modifiable risk factors associated with smoking in U.S.
      Air Force recruits may prove useful in developing smoking prevention programs. We
      assessed 257 recruits for selected psychosocial factors previously found to be
      associated with smoking in young adults in the general population. Cross
      sectional analysis revealed significant differences between smokers and
      nonsmokers for six of the eight factors addressed. Implications for the
      development of smoking prevention programs are discussed.

PMID- 9575767
TI  - Polymerase chain reaction: a link to the future.
AB  - Polymerase chain reaction (PCR) is a multi-faceted technology that is advancing
      disease detection. For pathology and clinical laboratories, PCR will be the tool
      of choice into the next century as scientists continue to develop and refine new
      uses. An amazingly simple process that amplifies nucleic acid sequences, PCR will
      change the practice of medicine because it will play a role in all aspects of the
      patient care continuum from diagnosis to treatment monitoring. Some striking
      applications range from detecting infectious and inherited diseases to assessing
      pharmacologic interventions. Additionally, the remarkable sensitivity of PCR will
      allow determination of a patient's genetic predisposition to diseases, thereby
      improving prevention modalities. Thus, medical practitioners should gain a basic
      understanding of this phenomenal cornerstone of molecular diagnostics. This
      article briefly reviews the history, theory, and uses of PCR and discusses
      relevant applications for military medicine.

PMID- 9575768
TI  - Musculoskeletal injuries in officer training: one-year follow-up.
AB  - This study attempts to map the incidence and types of musculoskeletal injury
      during officer training. Officer cadets from three training schools (N = 321)
      were monitored through a 1-year training course. A total of 278 injuries were
      sustained by 194 of the 321 cadets (60%). The incidence was highest during an
      introductory 5- or 6-week period of intensive basic training. During this period,
      rates at various training schools ranged from 26.7 to 45.5 injuries per 100 cadet
      months, which was five to nine times higher than during the rest of the year. The
      most common types of injury were overuse knee injuries, periostitis or
      compartment syndromes, Achilles tendinitis, and sprains of joint capsules or
      ligaments. Women and older cadets sustained more injuries than their respective
      male (p = 0.02) or younger (p = 0.02) counterparts. The study shows that
      musculoskeletal injuries occur frequently during officer training, especially
      during the first weeks. Recommendations for injury prevention include a more
      gentle start with slower progression in strain, slow introduction of combat
      boots, and differentiation of strain according to individual risk factors such as
      age and gender.

PMID- 9575770
TI  - A system for tracking dental readiness in the Air Force Reserve.
AB  - The potential of dental emergencies to reduce combat effectiveness is a major
      concern of military planners. The dental fitness classification is teh primary
      measure of an airman's dental readiness. A dental class 3 identification means
      that the airman has a dental condition that is likely to cause a dental emergency
      within 12 months. With few exceptions, Air Force Reserve command units are using
      only nonstandardized, manual tracking systems to ensure that identified members
      get needed dental treatment completed in a timely manner. The reliability and
      effectiveness of this process has been questioned in recent years. The importance
      of accurately recording the dental class status and having a reliable means to
      track dental treatment compliance of members designated dental class 3 is
      essential to maintaining a high state of dental readiness. A computerized
      tracking system called the Reserve Dental Data System was designed and developed
      to address this problem.

PMID- 9575769
TI  - Computer-assisted training program for simulation of triage, resuscitation, and
      evacuation of casualties.
AB  - The purpose of this paper is to introduce a multimedia computer software package
      that has been developed for the Federal Armed Forces of Germany to train military
      physicians in trauma management. The program presents different groups of
      casualties with characteristic wounds and multiple injuries on a CD-ROM and
      provides many clinical options at each decision point. Automatically evaluating
      the decisions for accuracy, the objective of the program is to train for triage,
      resuscitation, and evacuation of wounded in combat under pressure of time. The
      computer-assisted instruction program is inexpensive and allows easily accessible
      self-instruction as a supplement to formal classroom training. Using this
      teaching software, it may be possible to teach a standardized emergency case
      management algorithm for battlefield trauma. There was a high level of acceptance
      for this type of instruction. This is encouraging for medical educators involved
      in producing multimedia packages for teaching emergency medicine.

PMID- 9575771
TI  - An unusual case of Plasmodium vivax infection from Korea with delayed
      presentation.

PMID- 9575772
TI  - Parathyroid carcinoma: report of three cases and review of the literature.
AB  - Parathyroid carcinoma is a rare endocrine malignancy characterized by the
      exaggerated metabolic effects of the parathyroid glands. The preoperative
      differential diagnosis between parathyroid carcinoma and primary
      hyperparathyroidism is often difficult because many of the signs and symptoms are
      very similar. Intraoperative differentiation is obscured by the strict anatomic
      and histologic criteria required for diagnosis of parathyroid carcinoma. We have
      encountered three patients with parathyroid carcinoma during the last 10 years
      and managed them successfully. Two of them presented with recurrence of
      hypercalcemia, one 11 years after and the other 3 years after the primary
      operation for hyperparathyroidism; both patients were eventually diagnosed with
      parathyroid carcinoma. The third case was suspected as primary
      hyperparathyroidism preoperatively but confirmed as carcinoma subsequent to
      histologic examination.

PMID- 9575773
TI  - Mary J. Nielubowicz Award. Sexual risk behaviors among ship- and shore-based Navy
      women.
AB  - It is appropriate to study sexual risk behaviors among ship- and shore-based
      active duty Navy women. Morbidity and mortality associated with sexually
      transmitted diseases and human immunodeficiency virus/acquired immunodeficiency
      syndrome (HIV/AIDS), the increasing number of HIV/AIDS cases among heterosexual
      women, and the limited information regarding Navy women's sexual health are
      justification for identifying the determinants of sexual risk behavior(s) among
      this group of women of childbearing age. This study provides an integrated
      perspective in which demographic characteristics, motivation, problem-solving,
      self-esteem, and sexual risk behaviors are used to explore determinants of sexual
      risk behavior among ship- and shore-based Navy women. The subjects in the study
      (N = 165) consisted of 53 (32.5%) African-American and 88 (54%) white women whose
      average age was 26.89 years (SD = 6.10 years); the remaining 13.5% were from four
      other ethnic/racial groups. Sexual risk behaviors were defined as having more
      than one sex partner (n = 68) and the partner not using a condom (n = 75). Single
      women whose partners did not use condoms were observed to have lower self-esteem
      scores than single women whose partners used condoms (t = 3.37, df = 70.85, p =
      0.001). A knowledge of the factors that influence sexual risk behavior(s) will
      provide direction for the development of interventions to reduce risk.

PMID- 9575774
TI  - New York-Tidewater Chapters History of Military Medicine Essay Award. Surgical
      resection of the proximal humerus in the American Civil War.

PMID- 9575775
TI  - Sustaining membership lecture award. Dogma, the shade that blinds.
AB  - At the heart of medical science is the responsibility for investigators and
      practitioners to use the scientific method to seek and apply new knowledge to
      better understand the mechanisms, diagnosis, treatment, and prevention of
      disease. At times it is difficult to differentiate hypothesis or speculation from
      documented fact. This essay describes an episode in human biology and medicine in
      which authoritative speculation evolved into dogma and impeded investigators'
      proper interpretation of data about the pathogenesis of respiratory syncytial
      virus (RSV) bronchiolitis in infants. Speculation-turned-dogma regarding RSV
      seriously impeded scientific progress regarding RSV disease for nearly a
      generation. Teachers, biomedical scientists, and medical practitioners must
      remain vigilant for unsubstantiated dogma that can seriously impede progress in
      the medical sciences.

PMID- 9575776
TI  - Military disaster relief needs recognition.

PMID- 9575777
TI  - How was psychiatry offered?

PMID- 9575778
TI  - Questionnaire does not allow for accuracy.

PMID- 9575779
TI  - Living and dying with reactive species. Focus on "peroxynitrite induces apoptosis
      of HL-60 cells by activation of a caspase-3 family protease".

PMID- 9575780
TI  - Peroxynitrite induces apoptosis of HL-60 cells by activation of a caspase-3
      family protease.
AB  - Apoptosis is an active process critical for the homeostasis of organisms. Enzymes
      of the caspase family are responsible for executing this process. We have
      previously shown that peroxynitrite (ONOO-), a biological product generated from
      the interaction of nitric oxide and superoxide, induces apoptosis of HL-60 cells.
      The aim of this study was to elucidate the mechanisms involved in the execution
      process of peroxynitrite-induced apoptosis. Proteolytic cleavage of poly(ADP
      ribose) polymerase, an indication of caspase-3 family protease activation and an
      early biochemical event accompanying apoptosis, was observed in a time-dependent
      manner during peroxynitrite-induced apoptosis of HL-60 cells. Activation of
      caspase-3 during peroxynitrite-induced apoptosis was substantiated by monitoring
      proteolysis of the caspase-3 proenzyme and by measuring caspase-3 activity with a
      fluorogenic substrate. Furthermore, pretreatment of HL-60 cells with N-acetyl-Asp
      Glu-Val-Asp-aldehyde, a specific inhibitor of caspase-3, but not N-acetyl-Tyr-Val
      Ala-Asp-aldehyde, a specific inhibitor of caspase-1, decreased peroxynitrite
      induced apoptosis. These results suggest that the activation of a caspase-3
      family protease is essential for initiating the execution process of
      peroxynitrite-induced apoptosis of HL-60 cells.

PMID- 9575781
TI  - Elevated growth hormone increases the Ca2+ sensitivity of slow- and fast-twitch
      skeletal muscle of female rats.
AB  - To determine the effect of plasma growth hormone (GH) on skeletal muscle
      function, we measured the free Ca2+ concentration-tension relationship of slow
      twitch (soleus) and fast-twitch (peroneus longus) muscles isolated from rats
      undergoing acromegaly in response to implanted, GH-secreting tumors. Muscles from
      adult (9 mo) and aged rats (24 mo) were studied after the tumor-bearing rats
      weighted over 50% more than their age-matched controls. Ca(2+)-activated
      isometric tension was recorded from skinned muscle fibers. For soleus muscles,
      the free Ca2+ concentration producing 50% of maximal tension ([Ca2+]50) was 2.0
      microM for rats with tumors and 3.4-3.6 microM for controls. For peroneus longus
      fibers, [Ca2+]50 shifted from 6.1-6.7 microM in controls to 3.5 microM after
      tumors were introduced into either adult or aged rats. Soleus muscle fibers from
      neonatal rats (14 days) were less sensitive to Ca2+ than those isolated from
      adult rats, having a [Ca2+]50 of 7.3 microM. The Ca2+ sensitivity of peroneus
      longus fibers did not change with age. We conclude that significant increases in
      myofibrillar Ca2+ sensitivity occur in skeletal muscles undergoing rapid growth
      induced by GH-secreting tumors.

PMID- 9575782
TI  - Taurine synthesis and cysteine metabolism in cultured rat astrocytes: effects of
      hyperosmotic exposure.
AB  - We investigated mechanisms controlling taurine synthesis in cultured rat cerebral
      astrocytes. The mean +/- SE rate of taurine synthesis from extracellular cysteine
      was 21.2 +/- 2.0 pmol.mg protein-1.min-1, whereas taurine degradation was < 1.3%
      of this rate. Eliminating cellular glutathione and inhibiting glutathione
      biosynthesis increased taurine synthesis from extracellular cysteine by 39%. In
      cell homogenates, cysteine dioxygenase (CDO) and cysteine-sulfinate decarboxylase
      activities were 2.4 +/- 0.2 and 8.3 +/- 2.8 nmol.mg protein-1.min-1,
      respectively. CDO activity was strongly dependent on cysteine concentration over
      physiological and pathophysiological ranges of intracellular cysteine
      concentration. Growth in hyperosmotic medium caused a greater increase in culture
      medium taurine content than that measured from cells in isosmotic growth medium.
      Hyperosmotic treatment transiently increased the rate of cysteine accumulation
      and cellular cysteine and glutathione contents but had no effect on the synthesis
      rate of taurine from extracellular cysteine. Thus cysteine is accumulated and
      then metabolized to taurine through CDO, whose activity depends on the
      intracellular cysteine concentration and appears to be rate limiting for taurine
      synthesis. Hyperosmotic exposure increases net taurine production yet has no
      effect on taurine synthesis from exogenously applied cysteine. Availability of
      substrate from intracellular pools must contribute to maintenance of high
      intracellular taurine during hyperosmotic exposure.

PMID- 9575783
TI  - Bioelectric properties of human cystic fibrosis and non-cystic fibrosis fetal
      tracheal xenografts in SCID mice.
AB  - We measured, the bioelectric properties of 14 cystic fibrosis (CF) and 33 non-CF
      human fetal tracheal xenografts in severe combined immunodeficiency (SCID) mice.
      All xenografts exhibited a mature airway-type epithelium irrespective of their
      gestational age, duration of engraftment, and genotype. The in vivo potential
      difference and the in vitro baseline short-circuit current (Isc) were
      significantly higher in non-CF than in CF xenografts. In non-CF xenografts,
      sequential addition of amiloride, forskolin, and ATP resulted in a 39.4%
      decrease, a 24.1% increase, and a 43.6% increase in Isc, respectively. In CF
      xenografts, forskolin had no significant effect on Isc, whereas amiloride- and
      ATP-induced changes in Isc were proportionally higher than in non-CF xenografts (
      60.0 and +68.8%, respectively). These results indicate that the bioelectric
      properties of non-CF xenografts are similar to those of postnatal airways and
      that CF xenografts exhibit lower baseline electrogenic activity than non-CF
      xenografts but similar regulation of ion transport processes to postnatal CF
      airways. This model of mature human fetal tracheal mucosa may help gain insight
      into early CF airway pathogenesis.

PMID- 9575784
TI  - Intracellular acidification induced by passive and active transport of ammonium
      ions in astrocytes.
AB  - We describe an unconventional response of intracellular pH to NH4Cl in mouse
      cerebral astrocytes. Rapid alkalinization reversed abruptly to be replaced by an
      intense sustained acidification in the continued presence of NH4Cl. We
      hypothesize that high-velocity NH4+ influx persisted after the distribution of
      ammonia attained steady state. From the initial rate of acidification elicited by
      1 mM NH4Cl in bicarbonate-buffered solution, we estimate that NH4+ entered at a
      velocity of at least 31.5 nmol.min-1.mg protein-1. This rate increased with NH4Cl
      concentration, not saturating at up to 20 mM NH4Cl. Acidification was attenuated
      by raising or lowering extracellular K+ concentration. Ba2+ (50 microM) inhibited
      the acidification rate by 80.6%, suggesting inwardly rectifying K+ channels as
      the primary NH4+ entry pathway. Acidification was 10-fold slower in rat
      hippocampal astrocytes, consistent with the difference reported for K+ flux in
      vitro. The combination of Ba2+ and bumetanide prevented net acidification by 1 mM
      NH4Cl, identifying the Na(+)-K(+)-2Cl- cotransporter as a second NH4+ entry
      route. NH4+ entry via K+ transport pathways could impact "buffering" of ammonia
      by astrocytes and could initiate the elevation of extracellular K+ concentration
      and astrocyte swelling observed in acute hyperammonemia.

PMID- 9575785
TI  - Actions of substance P on membrane potential and ionic currents in guinea pig
      stellate ganglion neurons.
AB  - Neuropeptides are known to modulate the excitability of mammalian sympathetic
      neurons by their actions on various types of K+ and Ca2+ channels. We used whole
      cell patch-clamp recording methods to study the actions of substance P (SP) on
      dissociated adult guinea pig stellate ganglion (SG) neurons. Under current-clamp
      conditions, SG neurons exhibited overshooting action potentials followed by
      afterhyperpolarizations (AHP). The K+ channel blocker tetraethylammonium (1 mM),
      the Ca2+ channel blocker Cd2+ (0.1-0.2 mM), and SP (500 nM) depolarized SG
      neurons, decreased the AHP amplitude, and increased the action potential
      duration. In the presence of Cd2+, the effect of SP on membrane potential and AHP
      was reduced. Under voltage-clamp conditions, several different K+ currents were
      observed, including a transient outward K+ conductance and a delayed rectifier
      outward K+ current (IK) consisting of Ca(2+)-sensitive [IK(Ca)] and Ca(2+)
      insensitive components. SP (500 nM) inhibited IK. Pretreatment with Cd2+ (20-200
      microM) or the high-voltage-activated Ca2+ channel blocker omega-conotoxin (10
      microM) blocked SP's inhibitory effects on IK. This suggests that SP reduces IK
      primarily through the inhibition of IK(Ca) and that this may occur, in part, via
      a reduction of Ca2+ influx through voltage-dependent Ca2+ channels. SP's actions
      on IK were mediated by a pertussis toxin-insensitive G protein(s) coupled to NK1
      tachykinin receptors. Furthermore, we have confirmed that 500 nM SP reduced an
      inward Cd(2+)- and omega-conotoxin-sensitive Ba2+ current in SG neurons. Thus the
      actions of SP on IK(Ca) may be due in part to a reduction in Ca2+ influx
      occurring via N-type Ca2+ channels. This study presents the first description of
      ionic currents in mammalian SG neurons and demonstrates that SP may modulate
      excitability in SG neurons via inhibitory actions on K+ and Ca2+ currents.

PMID- 9575786
TI  - Basal chloride currents in murine airway epithelial cells: modulation by CFTR.
AB  - We have isolated ciliated respiratory cells from the nasal epithelium of wild
      type and cystic fibrosis (CF) null mice and used the patch-clamp technique to
      investigate their basal conductances. Current-clamp experiments on unstimulated
      cells indicated the presence of K+ and Cl- conductances and, under certain
      conditions, a small Na+ conductance. Voltage-clamp experiments revealed three
      distinct Cl- conductances. Itv-indep was time and voltage independent with a
      linear current-voltage (I-V) plot; Iv-act exhibited activation at potentials
      greater than +/- 50 mV, giving an S-shaped I-V plot; and Ihyp-act was activated
      by hyperpolarizing potentials and had an inwardly rectified I-V plot. The current
      density sequence was Ihyp-act = Iv-act >> Itv-indep. These conductances had Cl(-)
      to-N-methyl-D-glucamine cation permeability ratios of between 2.8 and 10.3 and
      were unaffected by tamoxifen, flufenamate, glibenclamide, DIDS, and 5-nitro-2-(3
      phenylpropylamino) benzoic acid but were inhibited by Zn2+ and Gd3+. Itv-indep
      and Iv-act were present in wild-type and CF cells at equal density and frequency.
      However, Ihyp-act was detected in only 3% of CF cells compared with 26% of wild
      type cells, suggesting that this conductance may be modulated by cystic fibrosis
      transmembrane conductance regulator (CFTR).

PMID- 9575787
TI  - Sulfhydryls associated with H2O2-induced channel activation are on luminal side
      of ryanodine receptors.
AB  - The mechanism underlying H2O2-induced activation of frog skeletal muscle
      ryanodine receptors was studied using skinned fibers and by measuring single
      Ca(2+)-release channel current. Exposure of skinned fibers to 3-10 mM H2O2
      elicited spontaneous contractures. H2O2 at 1 mM potentiated caffeine contracture.
      When the Ca(2+)-release channels were incorporated into lipid bilayers, open
      probability (Po) and open time constants were increased on intraluminal addition
      of H2O2 in the presence of cis catalase, but unitary conductance and reversal
      potential were not affected. Exposure to cis H2O2 at 1.5 mM failed to activate
      the channel in the presence of trans catalase. Application of 1.5 mM H2O2 to the
      trans side of a channel that had been oxidized by cis p
      chloromercuriphenylsulfonic acid (pCMPS; 50 microM) still led to an increase in
      Po, comparable to that elicited by trans 1.5 mM H2O2 without pCMPS. Addition of
      cis pCMPS to channels that had been treated with or without trans H2O2 rapidly
      resulted in high Po followed by closure of the channel. These results suggest
      that oxidation of luminal sulfhydryls in the Ca(2+)-release channel may
      contribute to H2O2-induced channel activation and muscle contracture.

PMID- 9575788
TI  - Sertoli cell expression of the cystic fibrosis transmembrane conductance
      regulator.
AB  - Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene
      have been associated with a number of male reproductive problems, including
      testis abnormalities and a reduction in germ cell quality and number. To
      establish at least one site of functional CFTR expression in the testis, we
      subjected cultured Sertoli cells to analysis of message, protein, and channel
      activity for CFTR. With reverse transcription-polymerase chain reaction, we
      obtained evidence for the presence of CFTR RNA when CFTR primers were used with
      RNA from cultured Sertoli cells. Western analysis performed with both anti-R and
      anti-C domain CFTR antibodies revealed immunoreactive material in extracts from
      primary Sertoli cell cultures that seemed consistent with CFTR previously
      identified in other cells and tissues. This led us to perform more detailed
      studies using the whole cell arrangement of the patch-clamp technique.
      Application of the membrane-soluble cAMP analog, 8-chlorophenyl-thio-cAMP,
      resulted in the activation of a Cl- current that displayed a permeability
      sequence of Br- > I- > or = Cl- and was blocked by diphenylamine-2-carboxylate
      and glibenclamide. In addition, a 13-pS conductance Cl- channel was measured in
      excised membrane patches exposed to the catalytic subunit of protein kinase A.
      When taken together, our findings of evidence of CFTR message, immunoreactive
      material that appeared consistent with CFTR, and Cl- channels with properties
      similar to those reported for CFTR provide strong evidence that Sertoli cells
      express a functional CFTR-like protein. The presence of CFTR in these cells may
      be needed to maintain the specific nutritional and fluid balance in the
      seminiferous tubule that is vital for normal spermatogenesis.

PMID- 9575789
TI  - Nerve growth factor regulates HCO3- absorption in thick ascending limb: modifying
      effects of vasopressin.
AB  - Growth factors stimulate Na+/H+ exchange activity in many cell types but their
      effects on acid secretion via this mechanism in renal tubules are poorly
      understood. We examined the regulation of HCO3- absorption by nerve growth factor
      (NGF) in the rat medullary thick ascending limb (MTAL), which absorbs HCO3- via
      apical membrane Na+/H+ exchange. MTAL were perfused in vitro with 25 mM HCO3-
      solutions (pH 7.4; 290 mosmol/kgH2O). Addition of 0.7 nM NGF to the bath
      decreased HCO3- absorption from 13.1 +/- 1.1 to 9.6 +/- 0.8 pmol.min-1.mm-1 (P <
      0.001). In contrast, with 10(-10) M arginine vasopressin (AVP) in the bath,
      addition of NGF to the bath increased HCO3- absorption from 8.0 +/- 1.6 to 12.5
      +/- 1.3 pmol.min-1.mm-1 (P < 0.01). Both effects of NGF were blocked by
      genistein, consistent with the involvement of tyrosine kinase pathways. However,
      the AVP-dependent stimulation required activation of protein kinase C (PKC),
      whereas the inhibition was PKC independent, indicating that the NGF-induced
      signaling pathways leading to inhibition and stimulation of HCO3- absorption are
      distinct. Hypertonicity blocked the inhibition but not the AVP-dependent
      stimulation, suggesting that hypertonicity and NGF may inhibit HCO3- absorption
      via a common mechanism. These data demonstrate that NGF inhibits HCO3- absorption
      in the MTAL under basal conditions but stimulates HCO3- absorption in the
      presence of AVP, effects that are mediated through distinct signal transduction
      pathways. They also show that AVP is a critical determinant of the response of
      the MTAL to growth factor stimulation and suggest that NGF can either inhibit or
      stimulate apical Na+/H+ exchange activity depending on its interactions with
      other regulatory factors. Locally produced growth factors such as NGF may play a
      role in regulating renal tubule HCO3- absorption.

PMID- 9575790
TI  - Evidence for Na+/Ca2+ exchange in intact single skeletal muscle fibers from the
      mouse.
AB  - The myoplasmic free Ca2+ concentration ([Ca2+]i) was measured in intact single
      fibers from mouse skeletal muscle with the fluorescent Ca2+ indicator indo 1.
      Some fibers were perfused in a solution in which the concentration of Na+ was
      reduced from 145.4 to 0.4 mM (low-Na+ solution) in an attempt to activate reverse
      mode Na+/Ca2+ exchange (Ca2+ entry in exchange for Na+ leaving the cell). Under
      normal resting conditions, application of low-Na+ solution only increased [Ca2+]i
      by 5.8 +/- 1.8 nM from a mean resting [Ca2+]i of 42 nM. In other fibers, [Ca2+]i
      was elevated by stimulating sarcoplasmic reticulum (SR) Ca2+ release with
      caffeine (10 mM) and by inhibiting SR Ca2+ uptake with 2,5-di(tert-butyl)-1,4
      benzohydroquinone (TBQ; 0.5 microM) in an attempt to activate forward-mode
      Na+/Ca2+ exchange (Ca2+ removal from the cell in exchange for Na+ influx). These
      two agents caused a large increase in [Ca2+]i, which then declined to a plateau
      level approximately twice the baseline [Ca2+]i over 20 min. If the cell was
      allowed to recover between exposures to caffeine and TBQ in a solution in which
      Ca2+ had been removed, the increase in [Ca2+]i during the second exposure was
      very low, suggesting that Ca2+ had left the cell during the initial exposure.
      Application of caffeine and TBQ to a preparation in low-Na+ solution produced a
      large, sustained increase in [Ca2+]i of approximately 1 microM. However, when
      cells were exposed to caffeine and TBQ in a low-Na+ solution in which Ca2+ had
      been removed, a sustained increase in [Ca2+]i was not observed, although [Ca2+]i
      remained higher and declined slower than in normal Na+ solution. This suggests
      that forward-mode Na+/Ca2+ exchange contributed to the fall of [Ca2+]i in normal
      Na+ solution, but when extracellular Na+ was low, a prolonged elevation of
      [Ca2+]i could activate reverse-mode Na+/Ca2+ exchange. The results provide
      evidence that skeletal muscle fibers possess a Na+/Ca2+ exchange mechanism that
      becomes active in its forward mode when [Ca2+]i is increased to levels similar to
      that obtained during contraction.

PMID- 9575791
TI  - Time-dependent stimulation by aldosterone of blocker-sensitive ENaCs in A6
      epithelia.
AB  - To study and define the early time-dependent response (< or = 6 h) of blocker
      sensitive epithelial Na+ channels (ENaCs) to stimulation of Na+ transport by
      aldosterone, we used a new modified method of blocker-induced noise analysis to
      determine the changes of single-channel current (iNa) channel open probability
      (Po), and channel density (NT) under transient conditions of transport as
      measured by macroscopic short-circuit currents (Isc). In three groups of
      experiments in which spontaneous baseline rates of transport averaged 1.06, 5.40,
      and 15.14 microA/cm2, stimulation of transport occurred due to increase of
      blocker-sensitive channels. NT varied linearly over a 70-fold range of transport
      (0.5-35 microA/cm2). Relatively small and slow time-dependent but aldosterone
      independent decreases of Po occurred during control (10-20% over 2 h) and
      aldosterone experimental periods (10-30% over 6 h). When the Po of control and
      aldosterone-treated tissues was examined over the 70-fold extended range of Na+
      transport, Po was observed to vary inversely with Isc, falling from approximately
      0.5 to approximately 0.15 at the highest rates of Na+ transport or approximately
      25% per 3-fold increase of transport. Because decreases of Po from any source
      cannot explain stimulation of transport by aldosterone, it is concluded that the
      early time-dependent stimulation of Na+ transport in A6 epithelia is due
      exclusively to increase of apical membrane NT.

PMID- 9575793
TI  - Determinants of slow gating in ClC-0, the voltage-gated chloride channel of
      Torpedo marmorata.
AB  - Membrane hyperpolarization normally activates the slow gate of the Torpedo
      voltage-gated chloride channel (ClC-0). To elucidate the structural basis of this
      process, carboxy terminus truncation mutants and chimeras were constructed,
      expressed in Xenopus oocytes, and evaluated using a two-microelectrode voltage
      clamp. Introduction of stop codons at several positions between transmembrane
      domains 12 and 13 (D12 and D13) showed no expression, whereas a truncation just
      after D13 yielded wild-type currents. A chimera (022) entailing the substitution
      of the carboxy-terminal cytoplasmic tail after Lys-520 with the corresponding
      region of ClC-2 lacked slow gating, whereas a more conservative construct
      (chimera 002), in which D13 was replaced with its ClC-2 analog, retained its
      capacity to slow gate. These findings suggest that important structures reside
      within the interdomain stretch (IDS) between D12 and D13. Unlike ClC-2, in which
      transplantation of "ball" structures could restore gating to constitutively open
      mutants, transplantation of the ClC-0 IDS to the amino terminus of chimera 022
      did not restore gating. Surprisingly, replacement of the IDS by the analogous
      regions of either ClC-1 or ClC-2 showed slow voltage-activated gating, although
      the gating was altered. Our findings lead us to conclude that both the functional
      expression and the slow voltage gating of ClC-0 rely on structures at the carboxy
      terminus of the channel.

PMID- 9575792
TI  - Inhibition of Ca(2+)-dependent Cl- secretion in T84 cells: membrane target(s) of
      inhibition is agonist specific.
AB  - Previous studies have indicated that Ca(2+)-dependent Cl- secretion across
      monolayers of T84 epithelial cells is subject to a variety of negative influences
      that serve to limit the overall extent of secretion. However, the downstream
      membrane target(s) of these inhibitory influences had not been elucidated. In
      this study, nuclide efflux techniques were used to determine whether inhibition
      of Ca(2+)-dependent Cl- secretion induced by carbachol, inositol 3,4,5,6
      tetrakisphosphate, epidermal growth factor, or insulin reflected actions at an
      apical Cl- conductance, a basolateral K+ conductance, or both. Pretreatment of
      T84 cell monolayers with carbachol or a cell-permeant analog of inositol 3,4,5,6
      tetrakisphosphate reduced the ability of subsequently added thapsigargin to
      stimulate apical 125I-, but not basolateral 86Rb+, efflux. These data suggested
      an effect on an apical Cl- channel. Conversely, epidermal growth factor reduced
      Ca(2+)-stimulated 86Rb+ but not 125I- efflux, suggesting an effect of the growth
      factor on a K+ channel. Finally, insulin inhibited 125I- and 86Rb+ effluxes. Thus
      effects of agents that inhibit transepithelial Cl- secretion are also manifest at
      the level of transmembrane transport pathways. However, the precise nature of the
      membrane conductances targeted are agonist specific.

PMID- 9575795
TI  - Activation of Ca(2+)-activated K+ (maxi-K+) channel by angiotensin II in myocytes
      of the guinea pig ileum.
AB  - We investigated the regulation of the Ca(2+)-activated K+ (maxi-K+) channel by
      angiotensin II (ANG II) and its synthetic analog, [Lys2]ANG II, in freshly
      dispersed intestinal myocytes. We identified a maxi-K+ channel population in the
      inside-out patch configuration on the basis of its conductance (257 +/- 4 pS in
      symmetrical 150 mM KCl solution), voltage and Ca2+ dependence of channel opening,
      low Na(+)-to-K+ and Cl(-)-to-K+ permeability ratios, and blockade by external Cs+
      and tetraethylammonium chloride. ANG II and [Lys2]ANG II caused an indirect,
      reversible, Ca(2+)- and dose-dependent activation of maxi-K+ channels in cell
      attached experiments when cells were bathed in high-K+ solution. This effect was
      reversibly blocked by DUP-753, being that it is mediated by the AT1 receptor.
      Evidences that activation of the maxi-K+ channel by ANG II requires a rise in
      intracellular Ca2+ concentration ([Ca2+]i) as an intermediate step were the shift
      of the open probability of the channel-membrane potential relationship to less
      positive membrane potentials and the sustained increase in [Ca2+]i in fura 2
      loaded myocytes. The preservation of the pharmacomechanical coupling of ANG II in
      these cells provides a good model for the study of transmembrane signaling
      responses to ANG II and analogs in this tissue.

PMID- 9575794
TI  - Differential translocation of protein kinase C isozymes by phorbol esters, EGF,
      and ANG II in rat liver WB cells.
AB  - The protein kinase C (PKC) family represents an important group of enzymes whose
      activation is associated with their translocation from the cytosol to different
      cellular membranes. In this study, the spatial distribution of PKC-alpha, -delta
      and -epsilon in rat liver epithelial (WB) cells has been examined by Western blot
      analysis after subcellular fractionation. Cytosolic, membrane, nuclear, and
      cytoskeletal fractions were obtained from cells stimulated with phorbol 12
      myristate 13-acetate (PMA), angiotensin II (ANG II), or epidermal growth factor
      (EGF). PMA caused most of the PKC-alpha, -delta and -epsilon initially present in
      the cytosol to be transported to the membrane and nuclear fractions. In contrast,
      both ANG II and EGF induced only a minor translocation of PKC-alpha to the
      membrane fraction but caused a statistically significant membrane-directed
      movement of PKC-delta and -epsilon. Translocation of PKC-delta and -epsilon to
      the nucleus induced by ANG II and EGF was transient and quantitatively smaller
      than that induced by PMA. PKC-delta and -epsilon were present in the cytoskeleton
      of resting cells, but although PMA, ANG II, and EGF caused some changes in their
      content, these were variable, suggesting that the cytoskeleton fraction was
      heterogeneous. PKC depletion inhibited ANG II-induced mitogenesis and the
      sustained activation of Raf-1 and extracellular regulated protein kinase (ERK).
      However, although PKC depletion inhibited EGF-induced mitogenesis, the maximum
      EGF-induced activation of the ERK pathway was only slightly retarded. We
      hypothesize that PKC-delta and -epsilon are involved in mitogenesis via both ERK
      dependent and ERK-independent mechanisms. These results support the notion that
      specific PKC isozymes exert spatially defined effects by virtue of their directed
      translocation to distinct intracellular sites.

PMID- 9575796
TI  - Regulation of cardiac AMP-specific 5'-nucleotidase during ischemia mediates ATP
      resynthesis on reflow.
AB  - The ability to resynthesize ATP during recovery from ischemia is limited to the
      size of endogenous pool of adenine nucleotides. Cytosolic AMP-specific 5'
      nucleotidase (5'-NT) plays a key role in ATP degradation and hence the capacity
      for ATP resynthesis. We have suggested (J. Clin. Invest. 93: 40-49, 1994) that
      intracellular acidosis [intracellular pH (pHi)] is a potent inhibitor of 5'-NT
      under in vivo conditions. To test this hypothesis further, we used the
      hyperthyroid rat heart because we could alter pHi during ischemia and determine
      the consequences of lower pHi on AMP accumulation (by chemical assay) and ATP
      resynthesis (by 31P nuclear magnetic resonance spectroscopy) during reperfusion.
      Global no-flow ischemia caused pHi to decrease from 7.1 under well-oxygenated
      control perfusion to 6.7. We found that decreasing pHi further from pH 6.7 to 6.4
      leads to increased accumulation (30%) of AMP during ischemia and to a 2.5-fold
      increase in ATP resynthesis during reperfusion. Analysis of all known substrates,
      products, activators, and inhibitors of the 5'-NT suggests that 5'-NT is
      activated primarily by Mg2+ and ADP and is inhibited by H+. Thus these
      observations provide evidence for a salutary effect of intracellular acidosis on
      preserving the AMP pool due to inhibition of 5'-NT and suggest a novel role of H+
      in protecting ischemic tissue.

PMID- 9575797
TI  - A volume-sensitive protein kinase regulates the Na-K-2Cl cotransporter in duck
      red blood cells.
AB  - When Na-K-2Cl cotransport is activated in duck red blood cells by either osmotic
      cell shrinkage, norepinephrine, fluoride, or calyculin A, phosphorylation of the
      transporter occurs at a common set of serine/threonine sites. To examine the
      kinetics and regulation of the activating kinase, phosphatase activity was
      inhibited abruptly with calyculin A and the subsequent changes in transporter
      phosphorylation and activity were determined. Increases in fractional
      incorporation of 32P into the transporter and uptake of 86Rb by the cells were
      closely correlated, suggesting that the phosphorylation event is rate determining
      in the activation process. Observed in this manner, the activating kinase was 1)
      stimulated by cell shrinkage, 2) inhibited by cell swelling, staurosporine, or N
      ethylmaleimide, and 3) unaffected by norepinephrine or fluoride. The inhibitory
      effect of swelling on kinase activity was progressively relieved by calyculin A,
      suggesting that the kinase itself is switched on by phosphorylation. The kinetics
      of activation by calyculin A conformed to an autocatalytic model in which the
      volume-sensitive kinase is stimulated by a product of its own reaction (e.g., via
      autophosphorylation).

PMID- 9575798
TI  - Circadian regulation of CREB transcription factor in mouse esophagus.
AB  - Very little is known about the circadian regulation of cell entry into the S and
      M phases of the cell cycle. Yet, in the mouse esophagus, a seven- to ninefold
      increase in DNA synthesis coincides with nocturnal feeding. The phosphorylation
      of the cAMP response element binding protein (CREB), a transcriptional factor,
      may regulate hypothalamic circadian rhythms in the brain. Here, we investigate
      the circadian regulation of CREB and Ser-133-phospho-CREB (PCREB) in the mouse
      esophagus by immunocytochemical and biochemical methods. We found that, during
      the dark phase, coincident with the onset of feeding and increased DNA synthesis,
      esophageal CREB and PCREB expression decreased. Although CREB-like
      immunoreactivity (CREB-lir) was expressed in many different cell types, it was
      concentrated in the mucosa, particularly in the replicating basal cell layer. The
      injection of epidermal growth factor, at a dosage known to maximally stimulate
      esophageal DNA synthesis in a 4- to 8-h period, rapidly decreased PCREB levels
      within 10 min of injection. We speculate that PCREB-lir may be involved in the
      circadian regulation of cell cycle events in the intact mouse esophagus.

PMID- 9575799
TI  - Identification of clathrin and clathrin adaptors on tubulovesicles of gastric
      acid secretory (oxyntic) cells.
AB  - gamma-Adaptin and clathrin heavy chain were identified on tubulovesicles of
      gastric oxyntic cells with the anti-gamma-adaptin monoclonal antibody (MAb) 100/3
      and an anti-clathrin heavy chain MAb (MAb 23), respectively. In Western blots,
      crude gastric microsomes from rabbit and rat and density gradient-purified, H-K
      ATPase-rich microsomes from these same species were immunoreactive for gamma
      adaptin and clathrin. In immunofluorescent labeling of isolated rabbit gastric
      glands, anti-gamma-adaptin and anti-clathrin heavy chain immunoreactivity
      appeared to be concentrated in oxyntic cells. In primary cultures of rabbit
      oxyntic cells, the immunocytochemical distribution of gamma-adaptin
      immunoreactivity was similar to that of the tubulovesicular membrane marker in
      oxyntic cells, the H-K-ATPase. Further biochemical characterization of the
      tubulovesicular gamma-adaptin-containing complex suggested that it has a subunit
      composition that is typical of that for a clathrin adaptor: in addition to the
      gamma-adaptin subunit, it contains a beta-adaptin subunit and other subunits of
      apparent molecular masses of 50 kDa and 19 kDa. From solubilized gastric
      microsomes from rabbit, gamma-adaptin could be copurified with the major cargo
      protein of tubulovesicles, the H-K-ATPase. Thus this tubulovesicular coat may
      bind directly to the H-K-ATPase and may thereby mediate the regulated trafficking
      of the H-K-ATPase at the apical membrane of the oxyntic cell during the gastric
      acid secretory cycle. Given the similarities of the regulated trafficking of the
      H-K-ATPase with recycling of cargo through the apical recycling endosome of many
      epithelial cells, we propose that tubulovesicular clathrin and adaptors may
      regulate some part of an apical recycling pathway in other epithelial cells.

PMID- 9575800
TI  - Inhibition of cell differentiation by G alpha q in the renal epithelial cell line
      LLC-PK1.
AB  - LLC-PK1, an epithelial cell line derived from the kidney proximal tubule, was
      used to study the ability of the G protein alpha-subunit, G alpha q, to regulate
      cell differentiation. A constitutively active mutant protein, alpha qQ209L, was
      expressed using the LacSwitch-inducible mammalian expression system. Induction of
      alpha qQ209L expression with isopropyl-beta-D-thiogalactopyranoside (IPTG)
      enhanced phospholipase C activity maximally by 6- to 7.5-fold. Increasing
      concentrations of IPTG progressively inhibited the activity of two
      differentiation markers, Na(+)-dependent hexose transport and alkaline
      phosphatase activity. Induction of alpha qQ209L expression also caused a change
      from an epithelial to a spindle-shaped morphology. The effects of alpha qQ209L
      expression on cell differentiation were similar to those observed with 12-O
      tetradecanoylphorbol 13-acetate (TPA) treatment. However, protein kinase C (PKC)
      levels were downregulated in TPA-treated cells but not in alpha qQ209L-expressing
      cells, suggesting that the regulation of PKC by G alpha q may be different from
      regulation by TPA. Interestingly, the PKC inhibitor GF-109203X did not inhibit
      the effect of IPTG on the development of Na(+)-dependent hexose transport in
      alpha qQ209L-expressing cells. These data implicate PKC delta and PKC epsilon in
      the pathway used by G alpha q to block the development of Na(+)-dependent hexose
      transport in IPTG-treated cells.

PMID- 9575801
TI  - Oxidant-induced arachidonic acid release and impairment of fatty acid acylation
      in vascular smooth muscle cells.
AB  - Oxidative damage, which plays a major role in the early stages of
      atherosclerosis, is associated with arachidonic acid (AA) release in vascular
      smooth muscle cells (VSMC) as in other cell types. In this study, H2O2 was used
      to investigate mechanisms of AA release from VSMC on oxidative stress. Cell
      treatment with H2O2 inhibited AA incorporation in an inverse relationship to
      prolonged H2O2-induced AA release. Identical kinetics of inhibition of AA
      incorporation and AA release were observed after cell treatment with AlF4-, a
      process not involving phospholipase A2 (PLA2) activation as recently described
      (A. Cane, M. Breton, G. Bereziat, and O. Colard. Biochem. Pharmacol. 53: 327-337,
      1997). AA release was not specific, since oleic acid also increased in the
      extracellular medium of cells treated with H2O2 or AlF4- as measured by gas
      chromatography-mass spectrometry. In contrast, AA and oleic acid cell content
      decreased after cell treatment. Oleoyl and arachidonoyl acyl-CoA synthases and
      acyltransferases, assayed using a cell-free system, were not significantly
      modified. In contrast, a good correlation was observed between decreases in AA
      acylation and cell ATP content. The decrease in ATP content is only partially
      accounted for by mitochondrial damage as assayed by rhodamine 123 assay. We
      conclude that oxidant-induced arachidonate release results from impairment of
      fatty acid esterification and that ATP availability is probably responsible for
      free AA accumulation on oxidative stress by preventing its reesterification
      and/or transmembrane transport.

PMID- 9575802
TI  - ANG II controls Na(+)-K+(NH4+)-2Cl- cotransport via 20-HETE and PKC in medullary
      thick ascending limb.
AB  - Cell pH was monitored in medullary thick ascending limbs to determine effects of
      ANG II on Na(+)-K+(NH4+)-2Cl- cotransport. ANG II at 10(-16) to 10(-12) M
      inhibited 30-50% (P < 0.005), but higher ANG II concentrations were stimulatory
      compared with the 10(-12) M ANG II level cotransport activity; eventually, 10(-6)
      M ANG II stimulated 34% cotransport activity (P < 0.003). Inhibition by 10(-12) M
      ANG II was abolished by phospholipase C (PLC), diacylglycerol lipase, or
      cytochrome P-450-dependent monooxygenase blockade; 10(-12) M ANG II had no effect
      additive to inhibition by 20-hydroxyeicosatetranoic acid (20-HETE). Stimulation
      by 10(-6) M ANG II was abolished by PLC and protein kinase C (PKC) blockade and
      was partially suppressed when the rise in cytosolic Ca2+ was prevented. All ANG
      II effects were abolished by DUP-753 (losartan) but not by PD-123319. Thus < or =
      10(-12) M ANG II inhibits via 20-HETE, whereas > or = 5 x 10(-11) M ANG II
      stimulates via PKC Na(+)-K+(NH4+)-2Cl- cotransport; all ANG II effects involve
      AT1 receptors and PLC activation.

PMID- 9575803
TI  - Age-dependent reductions in A1 adenosine receptor expression in rat testes.
AB  - The rat testis expresses high levels of A1 adenosine receptors (A1 AR) that
      couple to the inhibition of adenylyl cyclase activity. However, the physiological
      role of these receptors in the testis is not clear. Previous studies have
      documented a number of changes in the testis associated with the aging process.
      The goal of this study was to assess whether alteration in the expression and
      function of the testicular A1 AR occurs in aging, using the Fischer 344 rats as
      an aging model. Quantitation of A1 AR expression by radioligand binding of
      [3H]1,3-dipropyl-8-cyclopentylxanthine, an antagonist radioligand, indicates
      reductions in receptor number by 35 +/- 13.3 and 53 +/- 18.2% in 18- and 25-mo
      old rats, respectively, compared with 3-mo-old rats. Similar reductions in A1 AR
      expression were determined using Western blotting and receptor autoradiography.
      Quantitation of the Gi proteins using selective antibodies indicate age-dependent
      reductions in the levels of alpha i-1,2-, alpha i-3- and beta-subunits.
      Furthermore, the modulatory influences of guanosine 5'-O-(3-thiotriphosphate) on
      the binding of agonist and antagonist radioligands to the A1 AR were
      substantially reduced. Northern blotting analysis of rat testicular poly(A)+ RNA
      indicates both a 3.4-kb transcript and a 5.6-kb transcript that hybridized to the
      canine A1 AR cDNA probe. The levels of the 5.6-kb transcript were decreased by 24
      +/- 18 and 52 +/- 3% in the 18- and 25-mo-old rats, respectively, compared with
      the 3-mo-old rats. These results indicate age-dependent deficits in the A1 AR
      signal transduction pathway in the testes and predict concomitant reductions in
      the action of adenosine.

PMID- 9575805
TI  - Inhibition of proximal tubular fluid absorption by nitric oxide and atrial
      natriuretic peptide in rat kidney.
AB  - Atrial natriuretic factor (ANF) and nitric oxide (NO) stimulate production of
      guanosine 3',5'-cyclic monophosphate (cGMP) and are natriuretic. Split-drop
      micropuncture was performed on anesthetized rats to determine the effects of ANF
      and the NO donor sodium nitroprusside (SNP) on proximal tubular fluid absorption
      rate (Jva). Compared with control solutions, SNP (10(-4) M) decreased Jva by 23%
      when administered luminally and by 35% when added to the peritubular perfusate.
      Stimulation of fluid uptake by luminal angiotensin II (ANG II; 10(-9) M) was
      abolished by SNP (10(-4) and 10(-6) M). In proximal tubule suspensions, ANF (10(
      6) M) increased cGMP concentration to 143%, whereas SNP (10(-6), 10(-5), 10(-4),
      10(-3) M) raised cGMP to 231, 594, 687, and 880%, respectively. S-nitroso-N
      acetylpenicillamine (SNAP) also raised cGMP concentrations with similar dose
      response relations. These studies demonstrate inhibition by luminal and
      peritubular NO of basal and ANG II-stimulated proximal fluid absorption in vivo.
      The ability of SNP to inhibit basal fluid uptake whereas ANF only affected ANG II
      stimulated transport may be because of production of higher concentrations of
      cGMP by SNP.

PMID- 9575804
TI  - Growth factor-like phospholipids generated after corneal injury.
AB  - The present study provides evidence that growth factor-like glycerophosphate
      mediators of the lysophosphatidic acid (LPA) family are present in the aqueous
      humor and the lacrimal gland fluid of the rabbit eye. By use of a combination of
      HPLC, two-dimensional TLC, mass spectrometry, and the Xenopus oocyte bioassay,
      the LPA-like phospholipids LPA, cyclic PA, alkenyl-glycerophosphate (GP),
      lysophosphatidylserine, and phosphatidic acid were detected as physiological
      constituents of the fluids bathing the cornea. Corneal injury resulted in an
      increased production of some of these mediators. Alkenyl-GP, a novel member of
      the LPA family, has been identified in postinjury aqueous humor, establishing
      that it is generated endogenously. LPA and its homologues were found to be
      mitogenic in freshly dissociated keratocytes from uninjured corneas. There
      appears to be a link between the occurrence of LPA responsiveness in keratocytes
      activated by injury and the increase in LPA-like activity in aqueous humor. These
      data suggest that LPA and its homologues are involved in maintaining the
      integrity of the normal cornea and in promoting cellular regeneration of the
      injured cornea.

PMID- 9575806
TI  - Cloning and functional studies of splice variants of the alpha-subunit of the
      amiloride-sensitive Na+ channel.
AB  - The alpha-subunit of the amiloride-sensitive epithelial Na+ channel (alpha ENaC)
      is critical in forming an ion conductive pore in the membrane. We have identified
      the wild-type and three splice variants of the human alpha ENaC (h alpha ENaC)
      from the human lung cell line H441, using RT-PCR. These splice variants contain
      various structures in the extracellular domain, resulting in premature truncation
      (h alpha ENaCx), 19-amino acid deletion (h alpha ENaC-19), and 22-amino acid
      insertion (h alpha ENaC + 22). Wild-type h alpha ENaC and splice variants were
      functionally characterized in Xenopus oocytes by coexpression with hENaC beta-
      and gamma-subunits. Unlike wild-type h alpha ENaC, undetectable or substantially
      reduced amiloride-sensitive currents were observed in oocytes expressing these
      splice variants. Wild-type h alpha ENaC was the most abundantly expressed h alpha
      ENaC mRNA species in all tissues in which its expression was detected. These
      findings indicate that the extracellular domain is important to generate
      structural and functional diversity of h alpha ENaC and that alternative splicing
      may play a role in regulating hENaC activity.

PMID- 9575807
TI  - Reversible effects of acute hypertension on proximal tubule sodium transporters.
AB  - Acute hypertension provokes a rapid decrease in proximal tubule sodium
      reabsorption with a decrease in basolateral membrane sodium-potassium-ATPase
      activity and an increase in the density of membranes containing apical membrane
      sodium/hydrogen exchangers (NHE3) [Y. Zhang, A. K. Mircheff, C. B. Hensley, C. E.
      Magyar, D. G. Warnock, R. Chambrey, K.-P. Yip, D. J. Marsh, N.-H. Holstein
      Rathlou, and A. A. McDonough. Am. J. Physiol. 270 (Renal Fluid Electrolyte
      Physiol. 39): F1004-F1014, 1996]. To determine the reversibility and specificity
      of these responses, rats were subjected to 1) elevation of blood pressure (BP) of
      50 mmHg for 5 min, 2) restoration of normotension after the first protocol, or 3)
      sham operation. Systolic hypertension increased urine output and endogenous
      lithium clearance three- to fivefold within 5 min, but these returned to basal
      levels only 15 min after BP was restored. Renal cortex lysate was fractionated on
      sorbitol gradients. Basolateral membrane sodium-potassium-ATPase activity (but
      not subunit immunoreactivity) decreased one-third to one-half after BP was
      elevated and recovered after BP was normalized. After BP was elevated, 55% of the
      apical NHE3 immunoreactivity, smaller fractions of sodium-phosphate cotransporter
      immunoreactivity, and apical alkaline phosphatase and dipeptidyl-peptidase
      redistributed to membranes of higher density enriched in markers of the
      intermicrovillar cleft (megalin) and endosomes (Rab 4 and Rab 5), whereas density
      distributions of the apical cytoskeleton protein villin were unaltered. After 20
      min of normalized BP, all the NHE3 and smaller fractions of the other apical
      membrane proteins returned to their original distributions. These findings
      suggest that the dynamic regulation of proximal tubule sodium transport by acute
      changes in BP may be mediated by rapid reversible regulation of sodium pump
      activity and relocation of apical sodium transporters.

PMID- 9575808
TI  - Retinoids modulate P2U purinergic receptor-mediated changes in transcervical
      paracellular permeability.
AB  - In human cervical cells, extracellular ATP induces an acute decrease in the
      resistance of the lateral intercellular space, the phase I response, followed by
      a delayed increase in tight junctional resistance, the phase II response. These
      responses depend on vitamin A because incubation of cells in retinoid-free medium
      (RFM) abolished both responses. Treatment with retinoic acid restored the phase I
      response in full, but the amplitude of the phase II response was restored only
      partly. Shorter incubations and lower concentrations of retinoic acid [half
      maximal effective concentrations (K 1/2) = 0.1 microM] were required for
      restoring the phase I response than were required for reversing the phase II
      response (K 1/2 = 1 microM). The phase I response could be restored by ligands
      that bind to either retinoic acid receptors (RARs) or retinoid X receptors, but
      only RAR agonists had an effect on phase II response. RFM had no effect on
      decreases in resistance induced by ionomycin, but it attenuated phase II-like
      increases in resistance induced by KCl or by 1,2-dioctanoyl-sn-diglycerol (diC8).
      Actinomycin D blocked phase II response but not phase I response or the responses
      to ionomycin, KCl, or diC8. These results suggest that retinoids act on cervical
      cells via distinct retinoid receptor mechanisms and modulate phase I and phase II
      changes in resistance by regulating distinct signal mechanisms.

PMID- 9575810
TI  - Norepinephrine stimulates arachidonic acid release from vascular smooth muscle
      via activation of cPLA2.
AB  - The mechanism of agonist-activated arachidonate release was studied in segments
      of rat tail artery. Tail artery segments were prelabeled with [3H]arachidonate
      and then stimulated with norepinephrine (NE), and the radioactivity of the
      extracellular medium was determined. NE stimulated arachidonate release from the
      tissue without increasing arachidonic acid levels within cellular cytosol or
      crude membranes. About 90% of the extracellular radioactivity was shown to be
      unmetabolized arachidonate by TLC. Arachidonic acid release was not inhibited by
      the removal of the endothelium from the artery. NE exerted a half-maximal effect
      at a concentration of 0.2 microM. NE-stimulated arachidonate release was not
      inhibited by blockers of phospholipase C (U-73122), diacylglycerol lipase (RHC
      80267), secretory phospholipase A2 (manoalide), calcium-insensitive phospholipase
      A2 (HELSS), or beta-adrenergic receptors (propranolol). NE-stimulated arachidonic
      acid release was inhibited by blockers of cytosolic phospholipase A2 (cPLA2)
      (AACOCF3), alpha 1-adrenergic receptors (prazosin), and specific G proteins
      (pertussis toxin). This indicated that NE stimulated arachidonate release from
      vascular smooth muscle via activation of alpha-adrenergic receptors, either Gi or
      Go, and cPLA2. NE-activated arachidonic acid release from vascular smooth muscle
      may play a role in force generation by the tissue. Perhaps arachidonic acid
      extends the effect of NE on one specific smooth muscle cell to its nearby
      neighbor cells.

PMID- 9575809
TI  - Time-dependent modulation of capacitative Ca2+ entry signals by plasma membrane
      Ca2+ pump in endothelium.
AB  - In vascular endothelial cells, depletion of intracellular Ca2+ stores elicited
      capacitative Ca2+ entry (CCE) that resulted in biphasic changes of intracellular
      Ca2+ concentration ([Ca2+]i) with a rapid initial peak of [Ca2+]i followed by a
      gradual decrease to a sustained plateau level. We investigated the rates of Ca2+
      entry, removal, and sequestration during activation of CCE and their respective
      contributions to the biphasic changes of [Ca2+]i. Ca2+ buffering by mitochondria,
      removal by Na+/Ca2+ exchange, and a fixed electrical driving force for Ca2+
      (voltage-clamp experiments) had little effect on the CCE signal. The rates of
      entry of Mn2+ and Ba2+, used as unidirectional substitutes for Ca2+ entry through
      the CCE pathway, were constant and did not follow the concomitant changes of
      [Ca2+]i. Pharmacological inhibition of the plasma membrane Ca2+ pump, however,
      abolished the secondary decay phase of the CCE transient. The disparity between
      the biphasic changes of [Ca2+]i and the constant rate of Ca2+ entry during CCE
      was the result of a delayed, Ca(2+)-dependent activation of the pump. These
      results suggest an important modulatory role of the plasma membrane Ca2+ pump in
      the net cellular gain of Ca2+ during CCE.

PMID- 9575811
TI  - Contractile function and low-intensity exercise effects of old dystrophic (mdx)
      mice.
AB  - Old mdx mice display a severe myopathy almost identical to Duchenne's muscular
      dystrophy. This study examined the contractile properties of old mdx muscles and
      investigated any effects of low-intensity exercise. Isometric contractile
      properties of the extensor digitorum longus (EDL) and soleus muscles were tested
      in adult (8-10 mo) and old (24 mo, split into sedentary and exercised groups) mdx
      mice. The EDL and soleus from old mdx mice exhibited decreased absolute twitch
      and tetanic forces, and the soleus exhibited a > 50% decrease in relative forces
      (13.4 +/- 0.4 vs. 6.0 +/- 0.9 N/cm2) compared with adult mice. Old mdx muscles
      also showed longer contraction times and a higher percentage of type I fibers.
      Normal and mdx mice completed 10 wk of swimming, but mdx mice spent significantly
      less time swimming than normal animals (7.8 +/- 0.4 vs. 15.8 +/- 1.1 min,
      respectively). However, despite their severe dystrophy, mdx muscles responded
      positively to the low-intensity exercise. Relative tetanic tensions were
      increased (approximately 25% and approximately 45% for the EDL and soleus,
      respectively) after the swimming, although absolute forces were unaffected. Thus
      these results indicate that, even with a dystrophin-deficient myopathy, mdx
      muscles can still respond to low-intensity exercise. This study shows that the
      contractile function of muscles of old mdx mice displays many similarities to
      that of human dystrophic patients and provides further evidence that the use of
      non-weight-bearing, low-intensity exercises, such as swimming, has no detrimental
      effect on dystrophic muscle and could be a useful therapeutic aid for sufferers
      of muscular dystrophy.

PMID- 9575812
TI  - Myogenic NOS in canine lower esophageal sphincter: enzyme activation, substrate
      recycling, and product actions.
AB  - Depolarization elicited outward K+ currents from canine lower esophageal
      sphincter (LES) muscle cells, primarily through iberiotoxin (IbTX)- and
      tetraethylammonium-sensitive Ca(2+)-dependent K+ channels. Current magnitudes
      varied with pipette Ca2+ concentration (EC50 = 108.5 nM). NG-nitro-L-arginine (L
      NNA, 10(-4)M), IbTX (10(-8)M), or buffering intracellular Ca2+ to 8 nM decreased
      outward currents > 80%. Sodium nitroprusside (NaNP, 10(-4)M) restored L-NNA
      inhibited or low intracellular Ca2+ concentration (not IbTX)-inhibited currents.
      L-NNA or IbTX application depolarized LES cells from -43 to -35 mV. NaNP restored
      the membrane potential to -46 mV after L-NNA but not after IbTX application.
      Nifedipine (30 microM) reduced outward currents and abolished or reduced L-NNA or
      NaNP effects, respectively. Immunocytochemistry revealed the presence of both
      argininosuccinate synthetase and argininosuccinate lyase in LES muscle cells. L
      Citrulline, like L-arginine, reversed L-NNA inhibition of outward currents; only
      L-arginine reversed inhibition of outward currents by an antibody to
      argininosuccinate synthetase. Therefore, endogenous nitric oxide production,
      activated by Ca2+ entrance involving L-type Ca2+ channels, may continuously
      enhance outward currents to modulate LES muscle cell membrane potential and
      excitability.

PMID- 9575813
TI  - Model of beta-cell mitochondrial calcium handling and electrical activity. I.
      Cytoplasmic variables.
AB  - We continue our development of a kinetic model of bursting electrical activity in
      the pancreatic beta-cell (J. Keizer and G. Magnus. Biophys. J. 56: 229-242,
      1989), including the influence of Ca2+ handling by the mitochondria. Our minimal
      model of mitochondrial Ca2+ handling [G. Magnus and J. Keizer. Am. J. Physiol.
      273 (Cell Physiol. 42): C717-C733, 1997] is expanded to include the D-glucose
      dependence of the rate of production of mitochondrial reducing equivalents. The
      Ca2+ dependence of the mitochondrial dehydrogenases, which is also included in
      the model, plays only a small role in the simulations, since the dehydrogenases
      appear to be maximally activated when D-glucose concentrations are sufficient to
      produce bursting. A previous model of ionic currents in the plasma membrane is
      updated using a recent experimental characterization of the dependence of the
      conductance of the ATP-sensitive K+ (KATP) current on adenine nucleotides. The
      resulting whole cell model is complex, involving 12 dynamic variables that couple
      Ca2+ handling in the cytoplasm and the mitochondria with electrical activity in
      the plasma and inner mitochondrial membranes. Simulations with the whole cell
      model give rise to bursting electrical activity similar to that seen in
      pancreatic islets and clusters of pancreatic beta-cells. The full D-glucose dose
      response of electrical activity is obtained if the cytosolic rate of ATP
      hydrolysis is a sigmoidal function of glucose. The simulations give the correct
      shape, period, and phase of the associated oscillations in cytosolic Ca2+,
      predict that the conductance of the KATP current oscillates out of phase with
      electrical activity [as recently observed in ob/ob mice (O. Larsson, H. Kindmark,
      R. Branstrom, B. Fredholm, and P.-O. Berggren. Proc. Natl. Acad. Sci. USA 93:
      5161-5165, 1996)], and make other novel predictions. In this model, bursting
      results because Ca2+ uptake into mitochondria during the active phase reduces the
      mitochondrial inner membrane potential, reducing the rate of production of ATP,
      which in turn activates the KATP current and repolarizes the plasma membrane.

PMID- 9575814
TI  - Model of beta-cell mitochondrial calcium handling and electrical activity. II.
      Mitochondrial variables.
AB  - In the preceding article [Am. J. Physiol. 274 (Cell Physiol. 43): C1158-C1173,
      1998], we describe the development of a kinetic model for the interaction of
      mitochondrial Ca2+ handling and electrical activity in the pancreatic beta-cell.
      Here we describe further results of those simulations, focusing on mitochondrial
      variables, the rate of respiration, and fluxes of metabolic intermediates as a
      function of D-glucose concentration. Our simulations predict relatively smooth
      increases of O2 consumption, adenine nucleotide transport, oxidative
      phosphorylation, and ATP production by the tricarboxylic acid cycle as D-glucose
      concentrations are increased from basal to 20 mM. On the other hand, we find that
      the active fraction of pyruvate dehydrogenase saturates, due to increases in
      matrix Ca2+, near the onset of bursting electrical activity and that the
      NADH/NAD+ ratio in the mitochondria increases by roughly an order of magnitude as
      glucose concentrations are increased. The mitochondrial ATP/ADP ratio increases
      by factor of < 2 between the D-glucose threshold for bursting and continuous
      spiking. According to our simulations, relatively small changes in mitochondrial
      membrane potential (approximately 1 mV) caused by uptake of Ca2+ are sufficient
      to alter the cytoplasmic ATP/ADP ratio and influence ATP-sensitive K+ channels in
      the plasma membrane. In the simulations, these cyclic changes in the
      mitochondrial membrane potential are due to synchronization of futile cycle of
      Ca2+ from the cytoplasm through mitochondria via Ca2+ uniporters and Na+/Ca2+
      exchange. Our simulations predict steady mitochondrial Ca2+ concentrations on the
      order of 0.1 microM at low glucose concentrations that become oscillatory with an
      amplitude on the order of 0.5 microM during bursting. Abrupt increases in
      mitochondrial Ca2+ concentration > 5 microM may occur during continuous
      electrical activity.

PMID- 9575815
TI  - Unphysiological effects contributing to asparaginase toxicity in vitro.

PMID- 9575816
TI  - Properties and purification of a glucose-inducible human fatty acid synthase mRNA
      binding protein.
AB  - Glucose stabilizes the mRNA for human fatty acid synthase (FAS), an enzyme
      relevant to diverse human disorders, including hyperlipidemia, obesity, and
      malignancy. To determine the underlying mechanisms, RNA gel mobility shift assays
      were used to demonstrate that human Hep G2 cells contain a cytoplasmic factor
      that binds specifically to the 3'-terminus of the human FAS mRNA. D-Glucose
      increased RNA-binding activity by 2.02-fold (P = 0.0033), with activity peaking 3
      h after glucose feeding. Boiling or treatment of extracts with proteinase K
      abolished binding. Ultraviolet cross-linking of the FAS mRNA-binding factor
      followed by SDS-PAGE resolved a proteinase K-sensitive band with an apparent
      molecular mass of 178 +/- 7 kDa. The protein was purified to homogeneity using
      nondenaturing polyacrylamide gels as an affinity matrix. Acid phosphatase
      treatment of the protein prevented binding to the FAS mRNA, but binding activity
      was unaffected by modification of sulfhydryl groups and was not Mg2+ or Ca2+
      dependent. Deletion and RNase T1 mapping localized the binding site of the
      protein to 37 nucleotides characterized by the repetitive motif ACCCC and found
      within the first 65 bases of the 3'-UTR. Hybridization of the FAS transcript with
      an oligonucleotide antisense to this sequence abolished binding. These findings
      indicate that a 178-kDa glucose-inducible phosphoprotein binds to an (ACCCC)n
      containing sequence in the 3'-UTR of the FAS mRNA within the same time frame that
      glucose stabilizes the FAS message. This protein may participate in the
      posttranscriptional control of FAS gene expression.

PMID- 9575817
TI  - Measurement of dermal collagen synthesis rate in vivo in humans.
AB  - Accumulation of collagen produces organ dysfunction in many pathological
      conditions. We measured the fractional synthesis rate (FSR) of dermal collagen in
      five human volunteers from the increment of [13C]proline in detergent-soluble
      dermal collagen hydroxylated to hydroxyproline during a continuous infusion of L
      [1-13C]proline. In these and eight other volunteers, we measured [13C]proline
      enrichment in skin aminoacyl-tRNA, skin tissue fluid amino acid, and plasma. The
      prolyl-[13C]tRNA enrichment was one-half that in tissue fluid proline and more
      than threefold less than in plasma. The FSR of dermal collagen was 0.076 +/-
      0.063%/h (mean +/- SD), similar to previously reported rates for skeletal muscle
      contractile proteins and substantially slower than hepatically derived
      circulating proteins such as albumin or fibrinogen. We conclude that the FSR of
      human dermal collagen resembles that of other human proteins considered to
      display slow turnover. The current method for its measurement may be used to
      determine the regulation of collagen synthesis in other organs and disease
      states.

PMID- 9575818
TI  - Insulin sensitivity and glucose effectiveness: minimal model analysis of regular
      and insulin-modified FSIGT.
AB  - The minimal model is widely used to evaluate insulin action on glucose
      disappearance from frequently sampled intravenous glucose tolerance tests
      (FSIGT). The common protocols are a regular (rFSIGT, single injection of 0.3 g/kg
      of glucose) and an insulin-modified test (mFSIGT, with an additional insulin
      administration at 20 min). This study compared the insulin sensitivity index (SI)
      and glucose effectiveness (SG) obtained in the same individual (16 normal
      subjects) with the two tests. SI was 7.11 +/- 0.80 10(-4).min-1.microU-1.ml in
      rFSIGT and 6.96 +/- 0.83 in mFSIGT (P = 0.656), regression r = 0.92, P < 0.0001;
      SG was 0.0260 +/- 0.0028 min-1 and 0.0357 +/- 0.0052, respectively, statistically
      different (P = 0.013) but still with a good regression (r = 0.66, P = 0.0051). SG
      and insulin amount during the early period correlated (r = 0.6, P = 0.015 in
      rFSIGT and r = 0.76, P = 0.0006 in mFSIGT). In summary, both FSIGTs with minimal
      model analysis provide the same SI, which is a very robust index. SG was
      different by 28% due probably to the relationship between SG and the amount of
      circulating insulin. In studies comparing groups, the simpler rFSIGT can still be
      used with the advantage of accounting for endogenous insulin, thus offering the
      possibility of direct inferences on the beta-cell activity.

PMID- 9575819
TI  - Urate uptake and lowered ATP levels in human muscle after high-intensity
      intermittent exercise.
AB  - The exchange of purines in exercised and rested muscle and their relation to
      muscle ATP levels after intense intermittent exercise were investigated. Seven
      subjects performed one-legged knee extensor exercise on the following two
      occasions: without (control; C) and with (high purines; HP) additional arm
      exercise. There was a greater net release of hypoxanthine by the exercised muscle
      during the recovery period in HP compared with C [185 +/- 44 vs. 101 +/- 30 (SE)
      mumol/kg muscle; P < 0.05]. During recovery, the arterial urate concentration was
      higher in HP compared with C (peak: 585 +/- 48 vs. 355 +/- 20 mumol/l; P < 0.05).
      The exercised but not the rested muscle extracted a marked amount of urate (330
      mumol/kg muscle) from plasma in the HP trial. Muscle ATP levels after 90 min of
      recovery in HP were lower than at rest (24.3 +/- 0.6 vs. 20.1 +/- 1.1 mmol/kg dry
      wt). The present data suggest that a single session of long-term high-intensity
      intermittent exercise causes a significant release of purines from the muscle
      into blood, which contributes to a sustained lowered level of the muscle ATP
      concentration. Furthermore, intensely exercised muscle extracts urate when plasma
      urate is elevated, an event that may be of importance for the replenishment of
      oxidized muscle urate stores.

PMID- 9575820
TI  - The large variability in melatonin blood levels in ewes is under strong genetic
      influence.
AB  - The present study was conducted to assess the degree of genetic determination of
      the variability in the mean nocturnal plasma concentration of melatonin in sheep.
      Three hundred twelve ewes born from 18 males and with known genealogy were
      sampled at the summer and the winter solstices. The nocturnal plasma melatonin
      concentration was defined as the mean of four plasma samples taken at hourly
      intervals in the middle of the night (2200-0200). Identity of the father (P <
      0.001) and the solstice (P < 0.05) were significant. Melatonin concentrations
      varied considerably among individuals [338.4 +/- 197.5 (SD) pg/ml; range 26.6
      981.3 pg/ml] and between rams regarding the melatonin concentrations of their
      daughters (range from 202.9 to 456.3 pg/ml). Inheritance was analyzed by a
      statistical model that allows discrimination of genetic effects from nongenetic
      effects and that estimates repeatability and heritability coefficients. Both the
      repeatability coefficient between solstices (0.60) and heritability coefficient
      [0.45 +/- 0.07 (SE)] were high. These results demonstrate that the variability in
      plasma melatonin concentration in ewes is under strong genetic control.

PMID- 9575821
TI  - Phosphatidylinositol 3-kinase activation is required for insulin-stimulated
      sodium transport in A6 cells.
AB  - Insulin stimulates amiloride-sensitive sodium transport in models of the distal
      nephron. Here we demonstrate that, in the A6 cell line, this action is mediated
      by the insulin receptor tyrosine kinase and that activation of
      phosphatidylinositol 3-kinase (PI 3-kinase) lies downstream of the receptor
      tyrosine kinase. Functionally, a specific inhibitor of PI 3-kinase, LY-294002,
      blocks basal as well as insulin-stimulated sodium transport in a dose-dependent
      manner (IC50 approximately 6 microM). Biochemically, PI 3-kinase is present in A6
      cells and is inhibited both in vivo and in vitro by LY-294002. Furthermore, a
      subsequent potential downstream signaling element, pp70 S6 kinase, is activated
      in response to insulin but does not appear to be part of the pathway involved in
      insulin-stimulated sodium transport. Together with previous reports, these
      results suggest that insulin may induce the exocytotic insertion of sodium
      channels into the apical membrane of A6 cells in a PI 3-kinase-mediated manner.

PMID- 9575822
TI  - Ovine fetal leucine kinetics and protein metabolism during decreased oxygen
      availability.
AB  - The fetus depends on an uninterrupted supply of oxygen to provide energy, not
      only for basal metabolism but also for the metabolic costs of growth. By
      curtailing the metabolically expensive processes of protein turnover, the fetus
      could conserve energy when oxygen availability is limited. Therefore, this
      investigation was performed to find whether protein synthesis and breakdown are
      diminished during decreased fetal oxygen availability. Furthermore, if these
      conditions reduce fetal growth, protein synthesis should be affected more than
      breakdown so that protein accretion, an important component of fetal growth, also
      falls. In eight chronically prepared fetal lambs, we compared leucine kinetics
      (reciprocal pool model) during control conditions with measurements made during
      maternal hypoxia, a condition that limits fetal oxygen availability. Decreased
      fetal oxygen availability (-43%; P < 0.001) reduced fetal oxygen consumption (
      16%; P < 0.01), as well as both the uptake of leucine across the placenta (-48%;
      P < 0.001) and its rate of decarboxylation (-30%; P < 0.001). Fetal protein
      synthesis decreased (-32%; P < 0.001) to a greater extent than proteolysis (-22%;
      P < 0.001). Consequently, fetal protein accretion, an important component of
      fetal growth, also decreased (-62%; P < 0.001). We calculate that the reduction
      in fetal protein synthesis and breakdown, both processes that require
      intracellular expenditure of ATP, decreased fetal energy needs sufficiently to
      account for most, if not all, of the decrease measured in fetal oxygen
      consumption.

PMID- 9575823
TI  - Melanin-concentrating hormone: a functional melanocortin antagonist in the
      hypothalamus.
AB  - Melanin-concentrating hormone (MCH) and alpha-melanocyte-stimulating hormone
      (alpha-MSH) demonstrate opposite actions on skin coloration in teleost fish. Both
      peptides are present in the mammalian brain, although their specific
      physiological roles remain largely unknown. In this study, we examined the
      interactions between MCH and alpha-MSH after intracerebroventricular
      administration in rats. MCH increased food intake in a dose-dependent manner and
      lowered plasma glucocorticoid levels through a mechanism involving ACTH. In
      contrast, alpha-MSH decreased food intake and increased glucocorticoid levels.
      MCH, at a twofold molar excess, antagonized both actions of alpha-MSH. alpha-MSH,
      at a threefold molar excess, blocked the orexigenic properties of MCH. MCH did
      not block alpha-MSH binding or the ability of alpha-MSH to induce cAMP in cells
      expressing either the MC3 or MC4 receptor, the principal brain alpha-MSH receptor
      subtypes. These data suggest that MCH and alpha-MSH exert opposing and
      antagonistic influences on feeding behavior and the stress response and may
      function in a coordinate manner to regulate metabolism through a novel mechanism
      mediated in part by an MCH receptor.

PMID- 9575824
TI  - ERK2 mediates oxytocin-stimulated PGE2 synthesis.
AB  - Oxytocin (OT) induces PG synthesis by both uterine endometrial and amnion cells.
      We showed previously that CHO cells stably transfected with the rat oxytocin
      receptor (CHO-OTR cells) also synthesize PGE2 in response to OT. In the present
      work we have demonstrated that OTRs are coupled to both Gi and Gq/11, using
      immunoprecipitation of solubilized OTR complexes and ADP ribosylation. OT
      treatment caused the rapid phosphorylation of extracellular signal-regulated
      protein kinase 2 (ERK2 or p42MAPK), which was partially inhibited by pertussis
      toxin (PTX), consistent with OTR-Gi coupling. The PTX-insensitive portion of ERK2
      phosphorylation was linked to Gq, as inhibitors of both phospholipase C (U-73122)
      and protein kinase C (GF-109203X) blocked OT-induced ERK2 phosphorylation. OT
      stimulated c-fos expression was also mediated by ERK2 phosphorylation. The ERK-c
      fos pathway has been shown to be associated with cell proliferation, but OT had
      no effect on [3H]thymidine uptake by CHO-OTR cells. However, inhibition of OT
      induced ERK2 phosphorylation with an ERK kinase inhibitor (PD-98059) markedly
      reduced OT-stimulated PGE2 synthesis, pointing to the importance of ERK2
      activation in OT action.

PMID- 9575825
TI  - Time course of insulin action on tissue-specific intracellular glucose metabolism
      in normal rats.
AB  - We investigated the time course of insulin action in conscious rats exposed to
      constant physiological hyperinsulinemia (approximately 100 mU/l) while
      maintaining euglycemia (approximately 100 mg/dl) for 0, 0.5, 2, 4, 8, or 12 h. [3
      3H]glucose was infused to quantitate whole body glucose disposal (rate of
      disappearance, Rd), glycolysis (generation of 3H2O in plasma), hepatic glucoses
      production (HGP), and skeletal muscle and liver glycogen synthesis ([3-3H]glucose
      incorporation into glycogen and time-dependent change in tissue glycogen
      concentration). The basal Rd, which equals HGP, was 6.0 +/- 0.3 mg.kg-1.min-1.
      With increased duration of hyperinsulinemia from 0 to 0.5 to 2 to 4 h, Rd
      increased from 6.0 +/- 0.3 to 21.0 +/- 1.1 to 24.1 +/- 1.5 to 26.6 +/- 0.6 mg.kg
      1.min-1 (P < 0.05 for 2 and 4 h vs. 0.5 h). During the first 2 h the increase in
      Rd was explained by parallel increases in glycolysis and glycogen synthesis. From
      2 to 4 h the further increase in Rd was entirely due to an increase in glycolysis
      without change in glycogen synthesis. From 4 to 8 to 12 h of hyperinsulinemia, Rd
      decreased by 19% from 26.6 +/- 0.6 to 24.1 +/- 1.1 to 21.6 +/- 1.8 mg.kg-1.min-1
      (P < 0.05 for 8 h vs. 4 h and 12 h vs. 8 h). The progressive decline in Rd, in
      the face of constant hyperinsulinemia, occurred despite a slight increase (8-14%)
      in glycolysis and was completely explained by a marked decrease (64%) in muscle
      glycogen synthesis. In contrast, liver glycogen synthesis increased fourfold,
      indicating an independent regulation of muscle and liver glycogen synthesis by
      long-term hyperinsulinemia. In the liver, during the entire 12-h period of
      insulin stimulation, the contribution of the direct (from glucose) and the
      indirect (from C-3 fragments) pathways to net glycogen formation remained
      constant at 77 +/- 5 and 23 +/- 5%, respectively. HGP remained suppressed
      throughout the 12-h period of hyperinsulinemia.

PMID- 9575826
TI  - Adipose tissue metabolism in the postprandial period: microdialysis and
      arteriovenous techniques compared.
AB  - We investigated whether two different methods of studying metabolism in adipose
      tissue, microdialysis and the arteriovenous technique, produced comparable
      results during the postprandial period. Interstitial glycerol concentrations
      measured by microdialysis are usually used as an index of intracellular
      lipolysis, and it is not known whether they also reflect the intravascular action
      of lipoprotein lipase in the postprandial period. The two techniques were
      compared in 10 healthy subjects fed mixed meals. Interstitial glycerol
      concentrations reflected those measured in adipose tissue venous plasma. However,
      the calculation of the rate of glycerol release from adipose tissue using the
      microdialysis data differed systematically from that using arteriovenous
      difference measurement. The former method gave, on average, 40% lower values than
      the latter one. The difference is probably due to the assumptions that had to be
      made for the calculation of glycerol release. The two techniques have
      complementary places in the study of postprandial adipose tissue metabolism, with
      microdialysis reflecting intracellular hormone-sensitive lipase action rather
      than intravascular lipoprotein lipase.

PMID- 9575827
TI  - The cAMP-response element mediates induction of secretogranin II by CHX and FSK
      in GH4C1 cells.
AB  - The effect of cAMP on secretogranin II (SgII) gene transcription in GH4C1 (GH)
      cells is not observed unless protein synthesis is inhibited. We have defined
      elements in the SgII promoter that mediate regulation by cycloheximide (CHX) and
      forskolin (FSK) and characterized the nuclear proteins that interact with them.
      GH cells were transfected with p2774Luc, p351Luc, p242Luc, and p223Luc containing
      2,612, 189, 80, and 61 bp of the SgII promoter upstream of the luciferase gene,
      respectively. Treatment with CHX and FSK increased promoter activity 8- to 12
      fold in cells transfected with p2774Luc, p351Luc, and p242Luc but had not effect
      in cells transfected with p223Luc. The same 19-bp element (-80 to -62) mediates
      regulation by CHX alone, as CHX caused a 3.8-fold increase in activity in GH
      cells transfected with p242Luc but not p223Luc. Gel mobility shifts using
      sequences -84 to -53 resulted in three complexes, which contained cAMP response
      element-binding protein heterodimerized with cAMP response element modulator or
      activating transcription factor-1. No differences were observed in complex
      formation when cells were treated with either CHX, FSK, or CHX and FSK. Thus CHX
      affects the response to FSK in GH cells by inhibiting the synthesis of a protein,
      which does not itself interact with DNA or affect the binding of CRE-binding
      proteins with the SgII promoter, but likely interferes with the interaction of
      CRE-binding proteins with the general transcriptional machinery.

PMID- 9575828
TI  - On the mechanism of lactational anovulation in the rhesus monkey.
AB  - The relative roles of infant suckling and of maternal prolactin (PRL) secretion
      in lactational anovulation were studied in ovary-intact and ovariectomized rhesus
      monkeys nursing young that had been removed from their natural mothers.
      Hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity was
      monitored electrophysiologically in freely behaving animals by radiotelemetry.
      Serum luteinizing hormone, PRL, estradiol, and progesterone were also measured.
      Suckling inhibited GnRH pulse generator activity and ovarian cyclicity in all
      ovary-intact females but had no such effect on the pulse generator in long-term
      ovariectomized animals. When PRL secretion was suppressed by daily bromocriptine
      administration, GnRH pulse generator activity remained significantly inhibited
      and ovulation was prevented in four monkeys (6 trials), whereas in two females (6
      trials) a rapid increase in pulse generator frequency and the resumption of
      ovarian cyclicity were observed although suckling activity was maintained. One
      monkey displayed both response types. Although these results indicate that
      suckling per se is able to restrain GnRH pulse generator activity in the absence
      of PRL, they also suggest that the relative importance of these determinants is
      variable depending on factors that remain to be determined. The present study
      also confirms the permissive role of the ovary in the lactational suppression of
      GnRH pulse generator activity.

PMID- 9575829
TI  - High-protein meals do not enhance myofibrillar synthesis after resistance
      exercise in 62- to 75-yr-old men and women.
AB  - This study tested the hypothesis that increasing the protein content of
      isocaloric meals increases the rate of myofibrillar synthesis in muscle of
      healthy subjects over 60 yr old and enhances the stimulation of myofibrillar
      synthesis induced by resistance exercise. Myofibrillar synthesis of sedentary and
      exercised quadriceps muscle was determined by incorporation of L-[1-13C]leucine.
      During the tracer infusion, subjects consumed meals with a low (7% of energy, n =
      6)-, normal (14%, n = 6)-, or high (28%, n = 6)-protein content. In sedentary
      muscle, the mean (+/- SE) myofibrillar synthesis was 1.56 +/- 0.13%/day in the
      low-protein group, 1.73 +/- 0.11 %/day in the normal-protein group, and 1.76 +/-
      0.10%/day in the high-protein group (P = 0.42). Myofibrillar synthesis was faster
      in exercised muscle (mean 27%, P < 10(-6) in all groups (2.10 +/- 0.14%/day in
      low protein; 2.18 +/- 0.10%/day in normal protein; 2.11 +/- 0.09%/day in high
      protein; P = 0.84). The stimulation of myofibrillar synthesis by exercise was not
      significantly different among low-protein [0.54 +/- 0.12%/day (37 +/- 9%)],
      normal-protein [0.46 +/- 0.08%/day (28 +/- 5%)], and high-protein groups [0.34 +/
      0.04%/day (20 +/- 3%); P = 0.31]. We conclude that high-protein meals do not
      enhance the stimulation of myofibrillar protein synthesis induced by resistance
      exercise.

PMID- 9575830
TI  - Whole body and splanchnic metabolic, circulatory, and thermal effects of oral vs.
      intravenous fat administration.
AB  - Relatively few studies on the physiological effects of fat administration have
      been published. In the present study, whole body and splanchnic oxygen
      consumption, blood flow, blood temperature, glucose and insulin economy, and
      arterial and hepatic venous concentrations of hemoglobin, free fatty acids (FFA),
      and glycerol were measured by indirect calorimetry and catheterization technique
      in seven healthy men before and during 2.5 h after oral ingestion of 850 kJ of
      fat and in five healthy men before and during a 2.5-h intravenous (i.v.) infusion
      of 850 kJ of fat. Oral fat increased the splanchnic blood flow by 57 +/- 25%,
      reduced the plasma volume by 6 +/- 1%, reduced the arterial concentrations of FFA
      and glycerol by 33 +/- 7 and 50 +/- 16%, respectively, and increased arterial
      insulin concentration by 52 +/- 12% despite a simultaneous reduction in
      splanchnic insulin release, thus suggesting a reduction of the extrasplanchnic
      extraction of insulin. None of these effects occurred during intravenous fat
      infusion, and it is suggested that intestinal hormones might elicit these
      effects. Body heat content, unaffected after oral fat, increased by 67 +/- 20 kJ
      during intravenous fat infusion.

PMID- 9575831
TI  - Insulin stimulation of glucose uptake in skeletal muscles and adipose tissues in
      vivo is NO dependent.
AB  - The purpose of this study was to investigate whether in vivo nitric oxide
      synthase (NOS) inhibition influences insulin-mediated glucose disposal in rat
      peripheral tissues. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME)
      or saline was infused constantly during a hyperinsulinemic-euglycemic clamp in
      normal rats. Glucose utilization rates of insulin-sensitive tissues (individual
      muscles, heart, and adipose tissues) were simultaneously determined using tracer
      infusion of 2-deoxy-D-[3H]glucose (2-[3H]DG). NOS blockade with L-NAME resulted
      in significant (P < 0.05) reduction in both whole body glucose disposal (-16%, P
      < 0.01) and plasma 2-[3H]DG disappearance rate (-30%, P < 0.05) during hyper
      insulinemic-euglycemic clamp. L-NAME significantly decreased insulin-stimulated
      glucose uptake in heart (-62%, P = 0.01), soleus (-42%, P = 0.05), red (-53%, P <
      0.001) and white (-62%, P < 0.001) gastrocnemius, tibialis (-57%, P < 0.01), and
      quadriceps (-33%, P < 0.05) muscles. The NOS inhibitor also decreased insulin
      action in brown interscapular (-47%, P < 0.01), retroperitoneal (-52%, P = 0.07),
      and gonadal (-66%, P = 0.06) adipose tissues. In contrast to in vivo NOS
      blockade, L-NAME failed to affect basal or insulin-stimulated 2-[3H]DG transport
      in isolated soleus or extensor digitorum longus muscles in vitro. These results
      support the hypothesis that the action of insulin to augment glucose uptake by
      skeletal muscles and other peripheral insulin-sensitive tissues in vivo is NO
      dependent.

PMID- 9575832
TI  - Epinephrine translocates GLUT-4 but inhibits insulin-stimulated glucose transport
      in rat muscle.
AB  - We examined the effects of epinephrine (25, 50, and 150 nM) on 1) basal and
      insulin-stimulated 3-O-methylglucose (3-MG) transport in perfused rat muscles and
      2) GLUT-4 in skeletal muscle plasma membranes. Insulin increased glucose
      transport 330-600% in three types of skeletal muscle [white (WG) and (RG)
      gastrocnemius and soleus (SOL)]. Glucose transport was also increased by
      epinephrine (22-48%) in these muscles (P < 0.05). In contrast, the insulin
      stimulated 3-MG transport was reduced by epinephrine in all three types of
      muscles; maximal reductions were observed at 25 nM epinephrine in WG (-25%) and
      RG (-32.5%). A dose-dependent decrease occurred in SOL (-27% at 25 nM; -55% at
      150 nM, P < 0.05). Insulin (20 mU/ml) and epinephrine (150 nM) each translocated
      GLUT-4 to the plasma membrane, and no differences in translocation were observed
      between insulin and epinephrine (P > 0.05). In addition, epinephrine did not
      inhibit insulin-stimulated GLUT-4 translocation, and the combined epinephrine and
      insulin effects on GLUT-4 translocation were not additive. The increase in
      surface GLUT-4 was associated with increases in muscle cAMP concentrations, but
      only when epinephrine alone was present. No relationship was evident between
      muscle cAMP concentrations and surface GLUT-4 in the combined epinephrine and
      insulin-stimulated muscles. These studies indicate that epinephrine can
      translocate GLUT-4 while at the same time increasing glucose transport when
      insulin is absent, or can inhibit glucose transport when insulin is present.

PMID- 9575833
TI  - Ca(2+)-induced loss of Ca2+/calmodulin-dependent protein kinase II activity in
      pancreatic beta-cells.
AB  - Elevations in intracellular Ca2+ in electrically permeabilized islets of
      Langerhans produced rapid insulin secretory responses from beta-cells, but the
      Ca(2+)-induced secretion was not maintained and was irrespective of the pattern
      of administration of elevated Ca2+. Ca(2+)-insensitive beta-cells responded
      normally to activators of protein kinase C or cAMP-dependent kinase with
      increased insulin secretion. The loss of secretory responsiveness to Ca2+ was
      paralleled by a reduction in Ca(2+)-induced protein phosphorylation. This was
      caused by a reduction in Ca2+/calmodulin-dependent protein kinase II (CaMK II)
      activity in the desensitized cells, as assessed by measuring the phosphorylation
      of a CaMK II-specific exogenous substrate, autocamtide-2. The Ca(2+)-induced
      reductions in kinase activity and protein phosphorylation were not dependent on
      the activation of Ca(2+)-dependent protein kinases and were not caused by the
      activation of phosphoprotein phosphatases or of Ca(2+)-activated proteases. The
      concomitant reductions in CaMK II activity and Ca(2+)-induced insulin secretion
      suggest that the activation of CaMK II is required for normal insulin secretory
      responses to increased intracellular Ca2+ concentrations.

PMID- 9575834
TI  - Insulin secretion rates estimated by two mathematical methods in pancreas-kidney
      transplant recipients.
AB  - After pancreas-kidney transplantation, it is difficult to obtain an accurate
      estimate of the insulin secretion of the pancreas graft, since several pitfalls
      are involved using peripheral C-peptide and/or insulin measurements in this
      determination. In this study, the individual kinetic parameters of C-peptide and
      then the rates of insulin secretion were estimated by two mathematical methods,
      the deconvolution method and the "combined model" during slow (oral glucose) and
      fast (intravenous glucagon) changes in insulin secretion in six successful
      pancreas-kidney transplant recipients with systemic delivery of insulin (Px), six
      nondiabetic kidney-transplant recipients with portal insulin secretion (Kx), six
      nondiabetic controls (NS), and six C-peptide-negative insulin-dependent diabetes
      mellitus patients (IDDM). Decreased C-peptide clearance and basal and
      poststimulatory hyperinsulinemia were found in both Px and Kx compared with NS (P
      < 0.05). Similar glucose responses were observed after intravenous glucagon in
      all groups, whereas the responses after oral glucose were 30% higher in Px and Kx
      than in NS (P < 0.05). During oral glucose and after intravenous glucagon, both
      mathematical methods resulted in significantly lower maximal and incremental
      insulin secretion rates (ISR) in Px than in Kx (P < 0.05). In contrast,
      calculations of incremental ISR in NS and Px induced by the two beta-cell stimuli
      were about the same but significantly higher in Kx than in NS (P < 0.05). These
      results differed markedly from those obtained using peripheral measurements of
      insulin and C-peptide alone. In conclusion, when C-peptide clearance and insulin
      metabolism change, such as in pancreas-kidney transplant recipients, accurate
      evaluation of insulin secretion from the graft can be obtained only by using
      individual kinetics of the peptides before calculating the ISR. This study also
      clearly demonstrates that insulin secretion after pancreas transplantation is
      still defective.

PMID- 9575835
TI  - Effects of age, gender, and senescence on beta-adrenergic responses of isolated
      F344 rat brown adipocytes in vitro.
AB  - We previously reported greater age-related attenuation of cold-induced
      thermoregulation and brown adipose tissue thermogenic capacity in male vs. female
      F344 rats. With onset of the rapid weight loss that occurs near the end of the
      lifespan, this age-related attenuation becomes severe. We refer to this "end-of
      life" physiological state of older rats as senescence. Here, we measured oxygen
      consumption of isolated brown adipocytes and found no age (6 vs. 12 vs. 26 mo) or
      gender effects on maximal norepinephrine (NE)- or CL-316,243 (beta 3-adrenergic
      agonist)-induced responses. In contrast, brown adipocytes from 22- to 26-mo-old
      senescent rats (males and females) consumed 51-60% less oxygen during maximal
      stimulation with NE and CL-316,243 than did cells from 26-mo-old presenescent
      rats. This attenuation was associated with lower (65-72%) uncoupling protein 1
      concentrations but no alterations in NE-induced cAMP levels or lipolysis. Our
      data indicate that senescence, but not chronological age, significantly impacts
      NE-/beta 3-mediated thermogenesis of isolated brown adipocytes and that this
      effect involves altered mitochondrial rather than altered membrane or cytosol
      events.

PMID- 9575836
TI  - Effect of insulin on glycerol production in obese adolescents.
AB  - Impaired stimulation of glucose metabolism and reduced suppression of lipolytic
      activity have both been suggested as important defects related to the insulin
      resistance of adolescent obesity. To further explore the relationship between
      these abnormalities, we studied seven obese [body mass index (BMI) 35 +/- 2
      kg/m2] and seven lean (BMI 21 +/- 1 kg/m2) adolescents aged 13-15 yr and compared
      them with nine lean adults (aged 21-27 yr, BMI 23 +/- 1 kg/m2) during a two-step
      euglycemic-hyperinsulinemic clamp in combination with 1) a constant [2H5]glycerol
      (1.2 mg.m-2.min-1) infusion to quantify glycerol turnover and 2) indirect
      calorimetry to estimate glucose and net lipid oxidation rates. In absolute terms,
      basal glycerol turnover was increased and suppression by insulin was impaired in
      obese adolescents compared with both groups of lean subjects (P < 0.01). However,
      when the rates of glycerol turnover were adjusted for differences in body fat
      mass, the rates were similar in all three groups. Basal plasma free fatty acid
      (FFA) concentrations were significantly elevated, and the suppression by
      physiological increments in plasma insulin was impaired in obese adolescents
      compared with lean adults (P < 0.05). In parallel with the high circulating FFA
      levels, net lipid oxidation in the basal state and during the clamp was also
      elevated in the obese group compared with lean adults. Net lipid oxidation was
      inversely correlated with glucose oxidation (r = -0.50, P < 0.01). In conclusion,
      these data suggest that lipolysis is increased in obese adolescents (vs. lean
      adolescents and adults) as a consequence of an enlarged adipose mass rather than
      altered sensitivity of adipocytes to the suppressing action of insulin.

PMID- 9575837
TI  - Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation
      of the IGFBP-5 receptor.
AB  - The finding that insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5)
      binding to mouse osteoblasts was capable of being downregulated by IGFBP-5
      suggested that the 420-kDa membrane protein, which interacted with IGFBP-5, may
      be a signaling receptor (Andress, D. L. J. Biol. Chem. 270: 28289-28296, 1995).
      In the current study, a carboxy-terminal IGFBP-5 peptide, IGFBP-5-(201-218),
      which was found to competitively inhibit 125I-IGFBP-5 binding and to specifically
      bind to osteoblast monolayers, was used to affinity-purify the 420-kDa membrane
      protein. Co-incubation of the affinity-purified membrane protein with [32P]ATP
      resulted in autophosphorylation at serine residues. Serine phosphorylation of the
      420-kDa protein was enhanced by intact IGFBP-5, IGFBP-5-(1-169), and IGFBP-5-(201
      218). When the IGFBP-5 receptor was incubated with dephosphorylated casein in the
      presence of [32P]ATP, casein became phosphorylated on serine residues. These data
      indicate that IGFBP-5 stimulates the phosphorylation of the IGFBP-5 receptor and
      suggest that serine/threonine kinase activation may be important in mediating
      some of the IGF-independent effects of IGFBP-5.

PMID- 9575838
TI  - Signaling and sites of interaction for RX-871024 and sulfonylurea in the
      stimulation of insulin release.
AB  - The objective of this study was to compare effects of RX-871024, a compound with
      imidazoline structure, and the sulfonylurea glibenclamide, representatives of two
      groups of ATP-dependent potassium channel (KATP) blockers, on insulin secretion
      and cytoplasmic free calcium concentration ([Ca2+]i). Furthermore, we studied the
      interaction of the compounds on these two parameters. The experiments were
      performed in the perfused rat pancreas, isolated rat pancreatic islets, and
      dispersed beta-cells. At maximal effective concentrations of the compounds, RX
      871024 had a more pronounced insulinotropic effect than glibenclamide, but the
      increase in [Ca2+]i was similar. Glibenclamide enhanced the insulinotropic effect
      of suboptimal concentrations of RX-871024 at 3.3 and 16.7 mM glucose. Notably,
      glibenclamide and RX-871024 also stimulated insulin secretion under Ca(2+)
      clamped conditions, i.e., during plasma membrane depolarization with KCl and
      glucose or in permeabilized islets. The magnitudes of insulin stimulation under
      the latter types of conditions were similar for both compounds. It is concluded
      that RX-871024 and the sulfonylurea glibenclamide promote insulin secretion by
      two mechanisms, namely closure of KATP channels and a direct stimulation of
      exocytosis. At a similar increase in [Ca2+]i, the maximal stimulatory effect of
      RX-871024 on insulin secretion was stronger than that of glibenclamide, implying
      that RX-871024 also affects insulin secretion by a signal transduction pathway
      that is not activated by glibenclamide.

PMID- 9575839
TI  - Population-based modeling to demonstrate extrapancreatic effects of tolbutamide.
AB  - Tolbutamide is used increasingly as an investigative tool in in vivo studies of
      the physiology of glucose tolerance. Its hypoglycemic effect in nondiabetic
      subjects is widely variable, reflecting possible variability in its
      pharmacokinetics, an insulinergic response, an extrapancreatic effect of the
      drug, or the hypoglycemic effect of insulin itself. Using population-based
      modeling, we have investigated the kinetics and dynamics of tolbutamide and
      assessed covariates in two groups of healthy subjects. The results indicate a
      high variability in insulinergic effect, measured by the area under of the curve
      of insulin (0-60 min), in response to tolbutamide injection (coefficient of
      variation = 29-96%). However, it appears that impaired insulin sensitivity is
      compensated by higher insulin secretion in response to tolbutamide. Thus the
      hypoglycemic effect of high insulin secretion is minimal in insulin-resistant
      subjects. Application of the model indicated that tolbutamide has appreciable
      extrapancreatic effects mediated by prolongation of the residence time of insulin
      in a remote effect and by enhancement of glucose effectiveness. An effect in
      increasing the insulin sensitivity index is also possible but could not be
      confirmed statistically for all groups of subjects studied. These observations
      may explain inconsistencies between the results of tolbutamide and insulin
      injection in the frequently sampled intravenous glucose tolerance test and call
      for further study of insulin- vs. tolbutamide-modified frequently sampled
      intravenous glucose tolerance tests in the assessment of the insulin sensitivity
      and glucose effectiveness indexes.

PMID- 9575840
TI  - G protein-coupled receptors in gastrointestinal physiology. I. CCK receptors: an
      exemplary family.
AB  - The CCK and gastrin families of peptides act as hormones and neuropeptides on
      central and peripheral receptors to mediate secretion and motility in the
      gastrointestinal tract in the physiological response to a normal meal. Thus far,
      two CCK receptors have been molecularly identified to mediate the actions of CCK
      and gastrin, CCK-A and CCK-B receptors (CCK-AR and CCK-BR, respectively). The
      regulation of CCK-AR and CCK-BR affinity by guanine nucleotides and the receptor
      activation of G protein-dependent stimulation of phospholipase C and adenylyl
      cyclase suggested that they were guanine nucleotide-binding protein-coupled
      receptors [G protein-coupled receptors (GPCRs)]; however, the eventual cloning of
      their cDNAs revealed their heptahelical structure and confirmed their membership
      in the GPCR superfamily. The gastrointestinal system is a rich source of
      neuroendocrine hormones that interact with a large number of GPCRs to regulate
      the complex tasks of digestion, absorption, and excretion of a meal. This article
      focuses on the CCK family of GPCRs, and its activities in the gastrointestinal
      system.

PMID- 9575841
TI  - Current concepts in mucosal immunity. IV. How epithelial transport of IgA
      antibodies relates to host defense.
AB  - The humoral arm of the mucosal immune system is principally composed of locally
      synthesized polymeric IgA, whose Fc portion is adapted for binding to the
      polymeric immunoglobulin receptor that is expressed on the basolateral surface of
      mucosal epithelial cells, including enterocytes. This receptor mediates the
      endocytosis and transcytosis of polymeric IgA, which allows IgA to function in
      host defense at three anatomic levels in relation to mucosal epithelium: IgA
      antibodies in the lamina propria can bind antigens and excrete them through the
      epithelium into the lumen; antiviral IgA antibodies in transit through epithelial
      cells can inhibit virus production by an intracellular action; and IgA antibodies
      secreted into the lumen can prevent antigens and microbes from adhering to and
      penetrating the epithelium. The ways in which IgA antibodies function in mucous
      membranes provide challenging investigative opportunities for cell physiologists
      and cell biologists.

PMID- 9575842
TI  - In vivo signal-transduction pathways to stimulate phasic contractions in normal
      and inflamed ileum.
AB  - We investigated the in vivo signal-transduction pathways to stimulate phasic
      contractions in normal and inflamed ileum by close intra-arterial infusions of
      test substances. Methacholine stimulated phasic contractions dose dependently.
      This response was suppressed during inflammation. Verapamil inhibited the
      response to methacholine dose dependently in both normal and inflamed ileum.
      Neomycin inhibited the response partially in normal ileum and almost completely
      in inflamed ileum. H-7 and chelerythrine partially inhibited the methacholine
      response in normal ileum but had no significant effect in inflamed ileum.
      Ryanodine stimulated phasic contractions that were blocked by TTX, hexamethonium,
      atropine, or ruthenium red. Ruthenium red, however, had no significant effect on
      the contractile response to methacholine. CONCLUSIONS: 1) Ca2+ influx through the
      L-type channels may be the primary source of Ca2+ to stimulate in vivo phasic
      contractions. 2) Phosphatidylinositol hydrolysis enhances the stimulation of in
      vivo phasic contractions in the normal ileum. In the inflamed ileum,
      phosphatidylinositol hydrolysis may be essential to stimulate phasic
      contractions. 3) Inflammation may downregulate the protein kinase C pathway. 4)
      Ryanodine stimulates phasic contractions by the release of ACh.

PMID- 9575843
TI  - Dietary fatty acids are possible key determinants of cellular retinol-binding
      protein II gene expression.
AB  - We previously found that dietary unsaturated fatty acids increase cellular
      retinol-binding protein type II (CRBP II) mRNA and its protein levels in rat
      jejunum. To obtain insight into mechanisms for its gene induction, we
      investigated the effect of depletion of dietary fat on CRBP II mRNA levels and we
      further examined whether dietary retinol is necessary for dietary fat-induced
      CRBP II gene expression. Feeding the fat-free diet, which contained a sufficient
      amount of vitamin A, repressed CRBP II mRNA accumulation by 50% within 1 day, and
      this low level was sustained over the next 9 days. Parallel to the decreased CRBP
      II mRNA level, the peroxisomal proliferator-activated receptor-alpha (PPAR-alpha)
      mRNA level in rat jejunum was decreased by long-term (7 days) feeding of an
      isocaloric low-fat diet compared with the control. Oral administration of corn
      oil in the animals fed vitamin A-free diet elicited approximately threefold
      accumulation of CRBP II mRNA within 6 h. However, the administration of 9-cis
      retinoic acid brought about no accumulation of CRBP II mRNA. Even when rats were
      vitamin A-deficient, oral administration of corn oil, but not 9-cis-retinoic
      acid, caused an increase in jejunal CRBP II mRNA level. These results suggest
      that CRBP II gene expression in rat jejunum may be regulated predominantly by
      dietary fatty acids but little by dietary retinoids.

PMID- 9575844
TI  - Regulation of intestinal Cl- and HCO3-secretion by uroguanylin.
AB  - Uroguanylin is an intestinal peptide hormone that may regulate epithelial ion
      transport by activating a receptor guanylyl cyclase on the luminal surface of the
      intestine. In this study, we examined the action of uroguanylin on anion
      transport in different segments of freshly excised mouse intestine, using voltage
      clamped Ussing chambers. Uroguanylin induced larger increases in short-circuit
      current (Isc) in proximal duodenum and cecum compared with jejunum, ileum, and
      distal colon. The acidification of the lumen of the proximal duodenum (pH 5.0
      5.5) enhanced the stimulatory action of uroguanylin. In physiological Ringer
      solution, a significant fraction of the Isc stimulated by uroguanylin was
      insensitive to bumetanide and dependent on HCO3- in the bathing medium.
      Experiments using pH-stat titration revealed that uroguanylin stimulates serosal
      to-luminal HCO3- secretion (Js-->lHCO3-) together with a larger increase in Isc.
      Both Js-->lHCO3- and Isc were significantly augmented when luminal pH was reduced
      to pH 5.15. Uroguanylin also stimulated the Js-->lHCO3- and Isc across the cecum,
      but luminal acidity caused a generalized decrease in the bioelectric
      responsiveness to agonist stimulation. In cystic fibrosis transmembrane
      conductance regulator (CFTR) knockout mice, the duodenal Isc response to
      uroguanylin was markedly reduced, but not eliminated, despite having a similar
      density of functional receptors. It was concluded that uroguanylin is most
      effective in acidic regions of the small intestine, where it stimulates both HCO3
      and Cl-secretion primarily via a CFTR-dependent mechanisms.

PMID- 9575846
TI  - In vivo endotoxin enhances biliary ethanol-dependent free radical generation.
AB  - Endotoxemia is associated with alcoholic liver diseases; however, the effect of
      endotoxin on the oxidation of ethanol is not known. We tested the hypothesis that
      endotoxin treatment enhances hepatic ethanol radical production. The generation
      of free radicals by the liver was studied with spin-trapping technique utilizing
      the primary trap ethanol (0.8 g/kg) and the secondary trap alpha-(4-pyridyl-1
      oxide)-N-t-butylnitrone (4-POBN; 500 mg/kg). Electron paramagnetic resonance
      (EPR) spectra of bile showed six-line signals, which were dependent on ethanol,
      indicating the trapping of ethanol-dependent radicals. Intravenous injections of
      Escherichia coli lipopolysaccharide (0.5 mg/kg) 0.5 h before 4-POBN plus ethanol
      treatment caused threefold increases of biliary radical adducts. EPR analyses of
      bile from [1-13C]ethanol-treated endotoxic rats showed the presence of species
      attributable to alpha-hydroxyethyl adduct, carbon-centered adducts, and ascorbate
      radical. The generation of endotoxin-induced increases of ethanol-dependent
      radicals was suppressed by 50% on GdCl3 (20 mg/kg i.v.) or desferrioxamine
      mesylate (1 g/kg i.p.) treatment. Our data show that in vivo endotoxin increases
      biliary ethanol-dependent free radical formation and that these processes are
      modulated by Kupffer cell activation and catalytic metals.

PMID- 9575845
TI  - Effect of glucose supplementation on appetite and the pyloric motor response to
      intraduodenal glucose and lipid.
AB  - The effects of different macronutrients on appetite and pyloric motility and the
      impact of short-term dietary glucose supplementation on these responses were
      evaluated. Ten males (aged 19-38 yr) received isocaloric (2.9 kcal/min)
      intraduodenal infusions of glucose and lipid while antropyloroduodenal motility
      and appetite were assessed by manometry and visual analog scales, respectively.
      Effects of each intraduodenal nutrient on appetite and motility were evaluated
      before and after 7 days of dietary supplementation with glucose (400 g daily).
      Initially, both nutrients caused a similar rise in pyloric tone, but
      intraduodenal lipid was a more potent stimulus of phasic pyloric motility (P =
      0.05) and suppressed appetite more (P = 0.013) than intraduodenal glucose. After
      dietary glucose supplementation, the increase in pyloric tone during
      intraduodenal glucose was attenuated. Although intraduodenal lipid remained a
      more potent stimulant of phasic pyloric motility (P = 0.016), it no longer
      decreased appetite. We conclude that in healthy young males 1) intraduodenal
      infusion of lipid is a more potent stimulus of phasic pyloric motility and
      suppresses appetite more than intraduodenal glucose and 2) dietary glucose
      supplementation alters both the appetite suppressant effect of intraduodenal
      lipid and the pyloric motor response to intraduodenal glucose infusion.

PMID- 9575847
TI  - Regulation of hepatic neutral cholesteryl ester hydrolase by hormones and changes
      in cholesterol flux.
AB  - To understand molecular events in regulation of hepatic neutral cholesteryl ester
      hydrolase (EC3.1.1.13; CEH), catalytic activity, protein mass, and mRNA levels
      were measured in rats with various perturbations of hepatic cholesterol
      metabolism. Cholesterol feeding decreased activity (56 +/- 2%), mass (44 +/- 2%),
      and mRNA (14 +/- 3%). The cholesterol precursor mevalonate also decreased
      activity (42 +/- 6%), mass (76 +/- 3%), and mRNA (23 +/- 16%). Inhibition of
      cholesterol biosynthesis by lovastatin increased activity (65 +/- 12%) and mRNA
      (31 +/- 24%). Stimulation of cholesterol efflux by chronic biliary diversion
      increased activity (138 +/- 34%), mass (29 +/- 7%), and mRNA (146 +/- 28%).
      Chenodeoxycholate feeding decreased activity (46 +/- 6%) and mRNA (26 +/- 12%).
      These data suggest rational regulation of CEH in response to changes in
      cholesterol flux through the liver. In primary hepatocytes, steady-state mRNA
      markedly decreased during 72-h cultures and addition of L-thyroxine and
      dexamethasone synergistically maintained mRNA levels near control values.
      Lovastatin increased mRNA levels by 103 +/- 15%. Taurocholate and phorbol 12
      myristate 13-acetate suppressed mRNA (61 +/- 4% and 49 +/- 13%, respectively),
      suggesting that protein kinase C mediated effects of bile acids on CEH mRNA
      levels. These data suggest regulation of CEH by hormones and signal transduction
      in addition to changes in cholesterol flux.

PMID- 9575848
TI  - Estrogen increases sensitivity of hepatic Kupffer cells to endotoxin.
AB  - The relationship among gender, lipopolysaccharide (LPS), and liver disease is
      complex. Accordingly, the effect of estrogen on activation of Kupffer cells by
      endotoxin was studied. All rats given estrogen intraperitoneally 24 h before an
      injection of a sublethal dose of LPS (5 mg/kg) died within 24 h, whereas none of
      the control rats died. Mortality was prevented totally by pretreatment with
      gadolinium chloride, a Kupffer cell toxicant. Peak serum tumor necrosis factor
      alpha (TNF-alpha) values as well as TNF-alpha mRNA in the liver after LPS were
      twice as high in the estrogen-treated group as in the untreated controls. Plasma
      nitrite levels and inducible nitric oxide synthase in the liver were also
      elevated significantly in estrogen-treated rats 6 h after LPS. Furthermore,
      Kupffer cells isolated from estrogen-treated rats produced about twice as much
      TNF-alpha and nitrite as controls did in response to LPS. In addition, Kupffer
      cells from estrogen-treated rats required 15-fold lower amounts of LPS to
      increase intracellular Ca2+ than controls did, and Kupffer cells from estrogen
      treated animals expressed more CD14, the receptor for LPS/LPS binding protein,
      than controls. Moreover, estrogen treatment increased LPS binding protein mRNA
      dramatically in liver in 6-24 h. It is concluded that estrogen treatment in vivo
      sensitizes Kupffer cells to LPS, leading to increased toxic mediator production
      by the liver.

PMID- 9575849
TI  - Effect of cerebroventricular perfusion of bombesin on gastrointestinal
      myoelectric activity.
AB  - The effect of intracerebroventricular (i.c.v.) perfusion of bombesin (BBS) on the
      interdigestive migrating myoelectric complex (MMC) activity was examined in
      conscious dogs with electrodes implanted on the stomach and small intestine.
      Cannulas and a catheter were chronically positioned in the lateral and fourth
      cerebral ventricles, respectively. i.c.v. perfusion of BBS, which failed to
      increase plasma BBS levels, replaced phase I activity in the stomach and duodenum
      by intense irregular spike activity and decreased the occurrence rate of MMCs,
      whereas intravenous infusion of BBS evoked phase II-like activity, mainly in the
      jejunum and ileum, and suppressed phase III activity. These data suggest that the
      effect of i.c.v. administration of BBS was mediated by direct activation of
      central brain structures. During i.c.v. perfusion of BBS, cycling in plasma
      levels of motilin persisted even when phase III activity was absent and plasma
      levels of epinephrine rose significantly. Epinephrine infusion, however, did not
      affect myoelectric gastrointestinal activity except for prolonging phase II. Thus
      it is unlikely that the central action of BBS is exerted by motilin or
      epinephrine.

PMID- 9575850
TI  - Voltage-dependent K+ currents in smooth muscle cells from mouse gallbladder.
AB  - The ionic mechanisms associated with the control of gallbladder contractility are
      incompletely understood. One type of K+ current, the voltage-dependent K+ (KV)
      current, is relatively uncharacterized in gallbladder cells and may contribute to
      muscular excitability. The main focus of this study was therefore to determine
      the voltage dependence and pharmacological nature of this K+ current in isolated
      myocytes from mouse gallbladder, using the patch-clamp technique. Currents
      through Ca(2+)-activated K+ channels were minimized by buffering of intracellular
      Ca2+ (20 nM free Ca2+) and by inclusion of 1 mM tetraethylammonium (TEA+) in the
      bathing solution. With 140 mM symmetrical K+, membrane depolarization increased
      K+ currents, independent of driving force, as assessed by tail current analysis.
      Half-maximal activation of K+ currents occurred at approximately 1 mV and
      increased e-fold per 9 mV. Inactivation also increased on depolarization, with a
      midpoint of -24 mV. Single KV channels were recorded in the cell-attached
      configuration, exhibiting a single-channel conductance of 4.9 pS. TEA+ at 10 mM
      reduced KV currents by 36%. At +50 mV, 1 mM and 10 mM 4-aminopyridine inhibited
      currents by 18% and 35%, respectively, whereas 1 and 10 mM 3,4-diaminopyridine
      inhibited currents by 11% and 21%, respectively. Quinine inhibited KV currents
      (at +50 mV, 100 microM and 1 mM quinine inhibited current by 24% and 70%,
      respectively). In summary, we describe voltage-activated K+ currents from the
      mouse gallbladder that are likely to contribute to the control of muscular
      excitability.

PMID- 9575851
TI  - Developmental differences in response of mesenteric artery to acute hypoxia in
      vitro.
AB  - Studies were conducted to determine if the response of in vitro mesenteric artery
      from 3- and 35-day-old swine to acute hypoxia was age dependent. Isometric
      tension developed by mesenteric artery rings was measured using a standard
      myograph apparatus. When the buffer aeration gas was changed from 95% O2-5% CO2
      to 95% N2-5% CO2, phenylephrine-precontracted rings from both age groups
      consistently demonstrated a triphasic response, consisting of, in order, an
      initial, brief dilation, a sharp contraction, and a sustained loss of tone. The
      only portion of the triphasic response that was age dependent was the constrictor
      response, hypoxic vasoconstriction (HVC), which was significantly greater in
      rings from younger animals. HVC appeared to be mediated by a hypoxia-induced loss
      of constitutive nitric oxide production. Thus HVC was eliminated by endothelial
      removal, significantly attenuated by pretreatment with NG-monomethyl-L-arginine
      (L-NMMA), but not with NG-monomethyl-D-arginine, restored by coadministration of
      L-arginine, and accentuated by pretreatment with superoxide dismutase. Blockade
      of endothelin A receptors with BQ-610 or inhibition of cyclooxygenase or
      lipoxygenase activities with indomethacin or phenidone had no effect on HVC in
      either group. HVC appeared to be dependent on reduction in PO2, not on reduced
      ATP secondary to hypoxia, as it did not occur in rings administered 2,4
      dinitrophenol, an agent that uncouples oxidative phosphorylation. The magnitude
      of HVC, which appears to be mediated by hypoxia-induced supression of NO
      production, is greater in mesenteric artery from 3-day-old swine than from 35-day
      old swine.

PMID- 9575852
TI  - Cytosolic ionized Ca2+ modulates chemical hypoxia-induced hyperpermeability in
      intestinal epithelial monolayers.
AB  - We reported previously that ATP depletion induced by glycolytic inhibition or
      cellular hypoxia increases the permeability of intestinal epithelial monolayers
      [N. Unno, M. J. Menconi, A. L. Salzman, M. Smith, S. Hagen, Y. Ge, R. M. Ezzell,
      and M. P. Fink. Am. J. Physiol. 270 (Gastrointest. Liver Physiol. 33): G1010
      G1021, 1996]. In the present study, we examined the effects of the Ca2+ ionophore
      A-23187 or the intracellular ionized Ca2+ concentration ([Ca2+]i) chelator 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM on the
      permeability of enterocytic (T84) monolayers depleted of ATP by metabolic
      inhibition. Permeability was assessed by measuring transepithelial electrical
      resistance and the transepithelial flux of fluorescein sulfonic acid. Although
      neither A-23187 nor BAPTA-AM affected ATP depletion, A-23187 augmented, whereas
      BAPTA-AM ameliorated, chemical hypoxia-induced hyperpermeability. BAPTA-AM
      ameliorated chemical hypoxia-induced cytoskeletal derangements. Monolayers
      subjected to chemical hypoxia but incubated in a low (i.e., 100 microM) [Ca2+]
      environment showed preservation of junctional integrity, whereas voltage
      dependent Ca2+ channel blockers (NiCl2 or verapamil) failed to ameliorate
      chemical hypoxia-induced hyperpermeability. ATP depletion induces
      hyperpermeability in intestinal epithelial monolayers via a [Ca2+]i-dependent
      mechanism. Increased [Ca2+]i under these conditions reflects leakage of Ca2+ from
      the extracellular milieu via a mechanism unrelated to voltage-dependent Ca2+
      channels.

PMID- 9575853
TI  - CCK regulates nonselective cation channels in guinea pig gastric smooth muscle
      cells.
AB  - CCK has widespread effects in the gastrointestinal tract, stimulating pancreatic
      secretion and contraction of smooth muscles. The cellular mechanisms by which CCK
      causes smooth muscle contraction are poorly understood. We investigated the
      effects of CCK on guinea pig gastric smooth muscle cells using patch-clamp
      techniques. CCK caused contraction of cells accompanied by inward current. The
      conductance activated by CCK was nonselective for cations and showed little
      voltage dependence. Because ACh also activates nonselective cation current, we
      examined interactions between CCK and ACh. When CCK activated inward current, ACh
      caused no further effect. When CCK failed to activate current, subsequent ACh
      activated current was larger and no longer exhibited its characteristic voltage
      dependence. Intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate)
      caused similar changes in the voltage dependence of the ACh-activated current,
      suggesting a role for G proteins in regulation of the current. Activation of
      nonselective cation current would depolarize muscle and may contribute to the
      excitation mediated by CCK in tissues. These findings provide evidence that
      multiple types of receptors converge to regulate nonselective cation current.

PMID- 9575854
TI  - Dual role of CFTR in cAMP-stimulated HCO3- secretion across murine duodenum.
AB  - The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in
      cAMP-stimulated HCO3- secretion across the murine duodenum was investigated.
      Serosal-to-mucosal flux of HCO3- (Js-->m, in mu eq.cm-2.h-1) and short-circuit
      current (Isc; in mu eq.cm-2.h-1) were measured by the pH stat method in duodenum
      from CFTR knockout [CFTR(-)] and normal [CFTR(+)] mice. Under control conditions,
      forskolin increased Js-->m and Isc (+1.7 and +3.5, respectively) across the
      CFTR(+) but not CFTR(-) duodenum. Both the forskolin-stimulated delta Js-->m and
      delta Isc were abolished by the CFTR channel blocker 5-nitro-2-(3
      phenylpropylamino)benzoate, whereas inhibition of luminal Cl-/HCO3- exchange by
      luminal Cl- removal or DIDS reduced the Js-->m by approximately 18% without a
      consistent effect on the delta Isc. Methazolamide also reduced the Js-->m by 39%
      but did not affect the delta Isc. When carbonic anhydrase-dependent HCO3-
      secretion was isolated by using a CO2-gassed, HCO3(-)-free Ringer bath, forskolin
      stimulated the Js-->m and Isc (+0.7 and +2.0, respectively) across CFTR(+) but
      not CFTR(-) duodenum. Under these conditions, luminal Cl- substitution or DIDS
      abolished the Js-->m but not the delta Isc. It was concluded that cAMP-stimulated
      HCO3- secretion across the duodenum involves 1) electrogenic secretion via a CFTR
      HCO3- conductance and 2) electroneutral secretion via a CFTR-dependent Cl-/HCO3-
      exchange process that is closely associated with the carbonic anhydrase activity
      of the epithelium.

PMID- 9575855
TI  - Production and elimination of sulfur-containing gases in the rat colon.
AB  - Highly toxic sulfur-containing gases have been pathogenetically implicated in
      ulcerative colitis. Utilizing a rat model, we studied the production and
      elimination of sulfur-containing gases within the unperturbed colon. The major
      sulfur-containing gases were hydrogen sulfide (H2S), methanethiol, and dimethyl
      sulfide with cecal accumulation rates of 2.6, 0.096, and 0.046 microliter/min,
      respectively. The dependence of H2S production on dietary components was
      demonstrated via a sixfold reduction with fasting and a fivefold increase with
      carrageenan (a nonabsorbable, sulfur compound) feeding. Zinc acetate reduced
      cecal H2S by fivefold, indicating the importance of H2S binding by divalent
      cations. During passage from the cecum to the rectum, > 90% of the sulfur gases
      were absorbed or metabolized. An H2 35S turnover of 97%/min was observed in the
      isolated cecum. Thus mucosal exposure is > 10 times the measured accumulation
      rate. Cecal mucosal tissue very rapidly metabolized H2S and methanethiol via a
      nonmethylating reaction.

PMID- 9575856
TI  - Telenzepine-sensitive muscarinic receptors on rat pancreatic acinar cells.
AB  - To identify the muscarinic subtype present on the rat pancreatic acinar cell, we
      examined the effects of different muscarinic receptor antagonists on amylase
      secretion and proteolytic zymogen processing in isolated rat pancreatic acini.
      Maximal zymogen processing required a concentration of carbachol 10- to 100-fold
      greater (10(-3) M) than that required for maximal amylase secretion (10(-5) M).
      Although both secretion and conversion were inhibited by the M3 antagonist 4
      diphenylacetoxy-N-methyl-piperidine (4-DAMP) (50% inhibition approximately 6 x
      10(-7) M and 1 x 10(-8) M, respectively), the most potent inhibitor was the M1
      antagonist telenzepine (50% inhibition approximately 5 x 10(-10) M and 1 x 10(
      11) M, respectively). Pirenzepine, another M1 antagonist, and the M2 antagonist
      methoctramine did not reduce amylase secretion or zymogen processing in
      concentrations up to 1 x 10(-5) M. Analysis of acinar cell muscarinic receptor by
      PCR revealed expression of both m1 and m3 subtypes. The pancreatic acinar cell
      has a distinct pattern of muscarinic antagonist sensitivity (telenzepine >> 4
      DAMP > pirenzepine) with respect to both amylase secretion and zymogen
      conversion.

PMID- 9575857
TI  - Regulation of fundic and antral somatostatin secretion by CCK and gastrin.
AB  - CCK and gastrin stimulate somatostatin (SOM) secretion and thus modulate their
      direct effects on the parietal cell. Although SOM is stored in D cells of the
      fundus and antrum, the nature of the cell type differs, and it is not known
      whether both regions respond to the stimulatory effects of CCK and gastrin. The
      objectives of the present study were to determine the separate effects of CCK and
      gastrin on fundic and antral SOM secretion and to assess the type of receptor
      involved, using CCK-A (L-364,718) and CCK-B/gastrin (L-365,260) receptor
      antagonists. Changes in SOM were measured in plasma collected from cannulas
      draining blood from the fundus (gastric vein) and antrum (gastroepiploic vein) in
      anesthetized sheep. Both CCK and gastrin significantly stimulated SOM from the
      fundus and antrum. Sulfated CCK-8 (CCK-8S) increased SOM secretion from the
      fundus and antrum through interaction with both type A and B receptors. In
      contrast to CCK-8S, sulfated gastrin-17 (G-17S) stimulated SOM from the fundus
      via the type B receptor alone, whereas in the antrum G-17S stimulated SOM
      secretion independent of the A and B receptors. Histamine mediated, at least in
      part, the SOM-stimulatory effects; an H2-receptor antagonist blocked CCK
      stimulated SOM secretion in both the fundus and antrum and reduced gastrin
      stimulated SOM secretion in the fundus. The present study demonstrates regionally
      distinct regulatory mechanisms for gastric SOM secretion by CCK and gastrin.

PMID- 9575858
TI  - Active immunization against somatostatin alters regulation of gastrin in response
      to gastric acid secretagogues.
AB  - We have examined the coupling between somatostatin, gastrin, and gastric acidity,
      using sheep chronically immunized against somatostatin. All immunized sheep had
      high-titer (3.2 x 10(5) +/- 1.1 x 10(4) M), high-affinity (1.5 x 10(11) +/- 1.2 x
      10(10) l/mol) antibodies. However, basal gastrin and gastric acidity were similar
      to those in control animals, indicating that an inhibitory somatostatin tone was
      not required for the maintenance of normal basal gastrin and gastric acidity.
      Omeprazole (a proton pump inhibitor) increased gastric pH to a similar extent in
      both the control and immunized groups but resulted in a smaller increase in
      plasma gastrin in the immunized sheep, thus calling into question the assumption
      that hypergastrinemia associated with hypochlorhydria is the result of
      somatostatin withdrawal. Pentagastrin- or histamine-stimulated somatostatin
      secretion reversed or attenuated the omeprazole-induced hypergastrinemia in
      control but not immunized sheep, demonstrating a functional role for somatostatin
      and the biological efficacy of the somatostatin immunization. In a separate
      series of omeprazole-treated sheep, restoration of an acidic gastric pH with
      intragastric HCl reversed the hypergastrinemia in both control and immunized
      animals. We conclude that somatostatin is not essential for the acid-mediated
      regulation of gastrin. The use of a chronically immunized model as opposed to the
      acute administration of somatostatin antibodies has important advantages in
      determining the steady-state regulatory role of somatostatin.

PMID- 9575859
TI  - Ethanol-induced alterations of the microtubule cytoskeleton in hepatocytes.
AB  - Ethanol has been predicted to alter vesicle-based protein traffic in hepatocytes,
      in part, via a disruption of the microtubule (MT) cytoskeleton. However,
      information on the effects of chronic ethanol exposure on MT function in vivo is
      sparse. Therefore the goal of this study was to test for ethanol-induced changes
      in rat liver tubulin expression, assembly, and cellular organization, using
      molecular, biochemical and morphological methods. The results of this study
      showed that tubulin mRNA and protein levels were not altered by ethanol. Tubulin,
      isolated from control and ethanol-fed rats, showed similar polymerization
      characteristics as assessed by calculation of the critical concentration for
      assembly and morphological structure. In contrast, the total amount of assembly
      competent tubulin was reduced in livers from ethanol-fed rats compared with
      control rats when assessed by quantitative immunoblot analysis using a tubulin
      antibody. In addition, we observed that MT regrowth and organization in cultured
      hepatocytes treated with cold and nocodazole was markedly impaired by chronic
      ethanol exposure. In summary, these results indicate that tubulin levels in liver
      are not reduced by ethanol exposure. While there is a substantial amount of
      tubulin protein capable of assembling into functional MTs in ethanol-damaged
      livers, a marked portion of this tubulin is polymerization incompetent. This may
      explain why these hepatocytes exhibit a reduced number of MTs with an altered
      organization.

PMID- 9575860
TI  - Heterogeneity of the proliferative capacity of rat cholangiocytes after bile duct
      ligation.
AB  - We previously introduced the concept that intrahepatic bile duct epithelial
      cells, or cholangiocytes, are functionally heterogeneous. This concept is based
      on the observation that secretin receptor (SR) gene expression and secretin
      induced cAMP synthesis are present in cholangiocytes derived from large (> 15
      microns in diameter) but not small (< 15 microns in diameter) bile ducts. In work
      reported here, we tested the hypothesis that cholangiocytes are heterogeneous
      with regard to proliferative capacity. We assessed cholangiocyte proliferation in
      vivo by measurement of [3H]thymidine incorporation and in vitro by both
      [3H]thymidine incorporation and H3 histone gene expression in small (fraction 1)
      and large (fraction 2) cholangiocytes isolated from rats after bile duct ligation
      (BDL). In the two cholangiocyte subpopulations, we also studied basal
      somatostatin receptor (SSTR2) gene expression as well as the effects of
      somatostatin on 1) SR gene expression and secretin-induced cAMP synthesis and 2)
      [3H]thymidine incorporation and H3 histone gene expression. In normal rat liver,
      cholangiocytes, unlike hepatocytes, were mitotically dormant; after BDL,
      incorporation of [3H]thymidine markedly increased in cholangiocytes but not
      hepatocytes. When subpopulations of cholangiocytes were isolated after BDL, DNA
      synthesis assessed by both techniques was limited to large cholangiocytes, as was
      SSTR2 steady-state gene expression. In vitro, somatostatin inhibited SR gene
      expression and secretin-induced cAMP synthesis only in large cholangiocytes.
      Moreover, compared with no hormone, somatostatin inhibited DNA synthesis solely
      in large cholangiocytes. These results support the concept of the heterogeneity
      of cholangiocytes along the biliary tree, extend this concept to cholangiocyte
      proliferative activity, and imply that the proliferative compartment of
      cholangiocytes after BDL is located principally in the cholangiocytes lining
      large (> 15 microns) bile ducts.

PMID- 9575861
TI  - Role of PECAM-1 (CD31) in neutrophil transmigration in murine models of liver and
      peritoneal inflammation.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1) is thought to be critical
      for transendothelial migration of leukocytes, including neutrophils. Because
      neutrophil-mediated liver injury during endotoxemia is dependent on
      transmigration, we investigated the role of PECAM-1 in the pathophysiology of
      endotoxin-induced liver injury. Male C3Heb/FeJ mice were treated with
      galactosamine (Gal) and endotoxin (ET) (700 mg/kg Gal/100 micrograms/kg ET), and
      liver sections were stained for PECAM-1 expression. Control livers showed the
      presence of PECAM-1 on endothelial cells of large vessels but not in sinusoids.
      Gal/ET treatment did not change the expression pattern of PECAM-1. Gal/ET-induced
      liver injury (area of necrosis: 38 +/- 3%) was not attenuated by treatment with 3
      mg/kg of the antimurine PECAM-1 antibody 2H8. The antibody had no effect on
      sequestration and transmigration of neutrophils in sinusoids or the margination
      of neutrophils in large vessels. In contrast, 2H8 inhibited glycogen-induced
      neutrophil migration into the peritoneum by 74%; this effect correlated with
      PECAM-1 expression in the intestinal vasculature. Thus PECAM-1 is neither
      expressed nor inducible in hepatic sinusoids and is consequently not involved in
      neutrophil transmigration in the liver during endotoxemia. On the other hand,
      expression of PECAM-1 in mesenteric veins is critical for peritoneal neutrophil
      accumulation.

PMID- 9575862
TI  - One hundred years of journal publication.

PMID- 9575864
TI  - Carl J. Wiggers and the pulmonary circulation: a young man in search of
      excellence.
AB  - Oddly, Carl Wiggers (1883-1962), who is remembered for his work on the systemic
      circulation, may be considered the "American father of the pulmonary
      circulation." In nearly-20 papers published in the American Journal of Physiology
      between 1909 and 1925, he reported the first reliable pressure contours in the
      pulmonary artery, inquired into the relationship between respiration and
      pulmonary arterial pressure, examined right atrial and right ventricular
      function, and demonstrated how right and left heart dynamics relate to heart
      sounds. He also stimulated direct visualization of the lung microcirculation.
      Method and concept are inextricably linked in the progress of science. His
      contributions to the pulmonary circulation were based on his high-fidelity
      pressure and sound recording instruments, which he ultimately applied in the left
      heart. Wiggers' search for excellence in method brought him well-deserved fame in
      the systemic circulation, but the search began in the lung.

PMID- 9575865
TI  - Nitric oxide inhibits lung sodium transport through a cGMP-mediated inhibition of
      epithelial cation channels.
AB  - We used the patch-clamp technique to study the effect of nitric oxide (NO) on a
      cation channel in rat type II pneumocytes [alveolar type II (AT II) cells].
      Single-channel recordings from the apical surface of AT II cells in primary
      culture showed a predominant cation channel with a conductance of 20.6 +/- 1.1
      (SE) pS (n = 9 cell-attached patches) and Na(+)-to-K+ selectivity of 0.97 +/-
      0.07 (n = 7 cell-attached patches). An NO donor, S-nitrosoglutathione (GSNO; 100
      microM), inhibited the basal cation-channel activity by 43% [open probability
      (Po), control 0.28 +/- 0.05 vs. GSNO 0.16 +/- 0.03; P < 0.001; n = 16 cell
      attached patches], with no significant change in the conductance. GSNO reduced
      the Po by reducing channel mean open and increasing mean closed times. GSNO
      inhibition was reversed by washout. The inhibitory effect of NO was confirmed by
      using a second donor of NO, S-nitroso-N-acetylpenicillamine (100 microM; Po,
      control 0.53 +/- 0.05 vs. S-nitroso-N-acetylpenicillamine 0.31 +/- 0.04; -42%; P
      < 0.05; n = 5 cell-attached patches). The GSNO effect was blocked by methylene
      blue (a blocker of guanylyl cyclase; 100 microM), suggesting a role for cGMP. The
      permeable analog of cGMP, 8-bromo-cGMP (8-BrcGMP; 1 mM), inhibited the cation
      channel in a manner similar to GSNO (Po, control 0.38 +/- 0.06 vs. 8-BrcGMP 0.09
      +/- 0.02; P < 0.05; n = 7 cell-attached patches). Pretreatment of cells with 1
      microM KT-5823 (a blocker of protein kinase G) abolished the inhibitory effect of
      GSNO. The NO inhibition of channels was not due to changes in cell viability.
      Intracellular cGMP was found to be elevated in AT II cells treated with NO
      (control 13.4 +/- 3.6 vs. GSNO 25.4 +/- 4.1 fmol/ml; P < 0.05; n = 6 cell
      attached patches). We conclude that NO suppresses the activity of an Na(+)
      permeant cation channel on the apical surface of AT II cells. This action appears
      to be mediated by a cGMP-dependent protein kinase.

PMID- 9575866
TI  - Neonatal Clara cell toxicity by 4-ipomeanol alters bronchiolar organization in
      adult rabbits.
AB  - Nonciliated bronchiolar (Clara) cells metabolize environmental toxicants, are
      progenitor cells during development, and differentiate postnatally. Because
      differentiating Clara cells of neonatal rabbits are injured at lower doses by the
      cytochrome P-450-activated cytotoxicant 4-ipomeanol than are those of adults, the
      impact of early injury on the bronchiolar epithelial organization of adults was
      defined by treating neonates (3-21 days) and examining them at 4-6 wk.
      Bronchiolar epithelium of 6-wk-old animals treated on day 7 was most altered from
      that of control animals. Almost 100% of the bronchioles were lined by zones of
      squamous epithelial cells. Compared with control animals, the distal bronchiolar
      epithelium of 4-ipomeanol-treated animals had more squamous cells (70-90 vs. 0%)
      with a reduced overall epithelial thickness (25% of control value), fewer
      ciliated cells (0 vs. 10-20%), a reduced expression of Clara cell markers of
      differentiation (cytochrome P-4502B, NADPH reductase, and 10-kDa protein), and
      undifferentiated nonciliated cuboidal cell ultrastructure. We conclude that early
      injury to differentiating rabbit Clara cells by a cytochrome P-450-mediated
      toxicant inhibits bronchiolar epithelial differentiation and greatly affects
      repair.

PMID- 9575867
TI  - Dexamethasone activates expression of the PDGF-alpha receptor and induces lung
      fibroblast proliferation.
AB  - Corticosteroids (CSs) are commonly used for anti-inflammatory therapy in asthma
      and in interstitial lung diseases. In attempting to understand the mechanisms
      through which CSs control cell proliferation, we have carried out experiments to
      test the effects of dexamethasone (Dex) on the growth of lung fibroblasts. Using
      mouse 3T3 fibroblasts as well as early-passage rat lung fibroblasts (RLFs), we
      show that the quiescent cells in 1% serum or in serum-free media proliferate
      significantly in response to the addition of 10(-7) to 10(-9) M Dex. Increases as
      high as fourfold in cell numbers were recorded for the RLFs after 48 h in
      culture. A polyclonal antibody to the AB isoform of human platelet-derived growth
      factor (PDGF) blocked the proliferative response. As expected, the fibroblasts
      produced primarily PDGF-A chain, and the RLFs exhibited few PDGF-alpha receptors
      (PDGF-R alpha), the receptor type necessary for binding the AA isoform.
      Accordingly, we determined that Dex upregulated PDGF-R alpha mRNA and protein.
      Therefore, we can postulate that Dex-induced fibroblast proliferation is
      mediated, at least in part, by PDGF-AA, which binds to the PDGF-R alpha.

PMID- 9575868
TI  - H2O2 causes endothelial barrier dysfunction without disrupting the arginine
      nitric oxide pathway.
AB  - We have previously demonstrated that nitric oxide (.NO) donors attenuate and that
      inhibition of endogenous nitric oxide synthase (NOS) enhances hydrogen peroxide
      (H2O2)-mediated porcine pulmonary artery endothelial cell (PAEC) injury. The
      current study investigates the hypothesis that oxidant-mediated inhibition of NOS
      contributes to PAEC injury. PAEC barrier function, measured as the transmonolayer
      clearance of albumin, was significantly impaired by H2O2 (10-100 microM) in the
      absence of cytotoxicity. Treatment with H2O2 did not alter NOS activity, measured
      as the conversion of [3H]arginine to [3H]citrulline in PAEC lysates, either
      immediately after treatment with 0-250 microM H2O2 for 30 min or for up to 120
      min after treatment with 100 microM H2O2. H2O2 had little effect on NOS activity
      in intact PAECs, measured as 1) the formation of [3H]citrulline in [3H]arginine
      loaded PAECs, 2) PAEC guanosine 3',5'-cyclic monophosphate content, and 3)
      PAEC.NO release to the culture media. These results indicate that the arginine
      .NO pathway remains intact after exposure to oxidant conditions sufficient to
      promote functional derangements of vascular endothelial cells.

PMID- 9575869
TI  - Chronic hypoxia decreases nitric oxide production and endothelial nitric oxide
      synthase in newborn pig lungs.
AB  - To examine the effect of chronic hypoxia on nitric oxide (NO) production and the
      amount of the endothelial isoform of nitric oxide synthase (eNOS) in lungs of
      newborn piglets, studies were performed using 1- to 3-day-old piglets raised in
      room air (control) or 10% O2 (chronic hypoxia) for 10-12 days. Exhaled NO output
      and plasma nitrites and nitrates (collectively termed NOx-) were measured in
      anesthetized animals. NOx- concentrations were measured in the perfusate of
      isolated lungs. eNOS amounts were assessed in whole lung homogenates. In the
      intact piglets, exhaled NO outputs and plasma NOx- were lower in the chronically
      hypoxic (exhaled NO output = 0.2 +/- 0.1 nmol/min; plasma NOx- = 10.3 +/- 3.7
      nmol/ml) than in control animals (exhaled NO output = 0.8 +/- 0.2 nmol/min;
      plasma NOx- = 22.3 +/- 4.3 nmol/ml). In perfused lungs, the perfusate
      accumulation of NOx- was lower in chronic hypoxia (1.0 +/- 0.3 nmol/min) than in
      control (2.6 +/- 0.6 nmol/min) piglets. The amount of whole lung homogenate eNOS
      from the chronic hypoxia piglets was 40 +/- 8% less than that from the control
      piglets. The reduced NO production observed in anesthetized animals or perfused
      lungs of chronically hypoxic newborn piglets is consistent with the finding of
      reduced lung eNOS protein amounts. Decreased NO production might contribute to
      the development of chronic hypoxia-induced pulmonary hypertension in newborns.

PMID- 9575870
TI  - Myosin heavy chain gene expression changes in the diaphragm of patients with
      chronic lung hyperinflation.
AB  - In striated muscle, chronic increases in workload result in changes in myosin
      phenotype. The aim of this study was to determine whether such changes occur in
      the diaphragm of patients with severe chronic obstructive pulmonary disease, a
      situation characterized by a chronic increase in respiratory load and lung
      volume. Diaphragm biopsies were obtained from 22 patients who underwent thoracic
      surgery. Myosin was characterized with electrophoresis in nondenaturing
      conditions, SDS-glycerol PAGE, and Western blotting with monoclonal antibodies
      specific for slow and fast myosin heavy chain (MHC) isoforms. Flow volume curves,
      total lung capacity, and functional residual capacity were measured before
      surgery in 20 patients. We found that the human diaphragm is composed of at least
      four myosin isoforms, one slow and three fast, resulting from the combination of
      three MHC species. Chronic overload was associated with an increase in the slow
      beta-MHC species at the expense of the fast species (beta-MHC, 78.2 +/- 4.6 and
      50.0 +/- 6.5% in emphysematous and control patients, respectively; P < 0.005).
      Linear correlations were found between beta-MHC percentage and forced expiratory
      volume in 1 s (r = -0.52; P < 0.02), total lung capacity (r = 0.44; P < 0.05),
      and functional residual capacity (r = 0.65; P < 0.003). The human adult diaphragm
      is composed of a balanced proportion of slow and fast myosin isoforms. In
      patients with chronic obstructive pulmonary disease, the proportion of fast
      myosins decreases, whereas that of slow myosin increases. This increase appears
      to be closely related to lung hyperinflation and may reflect an adaptation of the
      diaphragm to the new functional requirements.

PMID- 9575871
TI  - Increased lung preproET-1 and decreased ETB-receptor gene expression in fetal
      pulmonary hypertension.
AB  - Endothelin (ET)-1, a potent vasoconstrictor and smooth muscle mitogen, is
      produced from its precursor, preproET-1, by endothelin-converting enzyme (ECE)-1
      activity. ET-1 may bind to two receptors, ETA and ETB, that mediate
      vasoconstriction and vasodilation in the ovine fetal lung, respectively. ET-1
      contributes to high pulmonary vascular resistance in experimental perinatal
      pulmonary hypertension induced by ligation of the ductus arteriosus in the fetal
      lamb. Physiological studies in this model have demonstrated enhanced ETA- and
      diminished ETB-receptor activities and a threefold increase in lung
      immunoreactive ET-1 protein content. We hypothesized that increased ET production
      and an imbalance in receptor expression would favor vasoconstriction and smooth
      muscle cell hypertrophy in pulmonary hypertension and may be partially due to
      alterations in gene expression. To test this hypothesis, we studied lung mRNA
      expression of preproET-1, ECE-1, and the ETA and ETB receptors in normal and
      hypertensive fetal lambs. Total RNA was isolated from whole lung tissue in normal
      late-gestation fetuses (135 +/- 3 days; 147 days = term) and from animals with
      pulmonary hypertension after ductus arteriosus ligation for 8 days (134 +/- 4
      days). Ductus arteriosus ligation increased right ventricular hypertrophy
      [control 0.56 +/- 0.02 vs. hypertension 0.85 +/- 0.05; right ventricle/(left
      ventricle + septum); P < 0.05]. Northern blot analysis was performed using cDNA
      probes and was normalized to the signal for 18S rRNA. We found a 71 +/- 24%
      increase in steady-state preproET-1 mRNA (P < 0.05) and a 62 +/- 5% decrease in
      ETB mRNA (P < 0.05) expression in ductus arteriosus ligation. ECE-1 and ETA
      receptor mRNA expression did not change. We conclude that chronic intrauterine
      pulmonary hypertension after ductus arteriosus ligation increases steady-state
      preproET-1 mRNA and decreases ETB-receptor mRNA without changing ECE-1 mRNA or
      ETA-receptor mRNA expression. These findings suggest that increased ET-1
      production and decreased ETB-receptor expression may contribute to increased
      vasoconstrictor tone in this experimental model of neonatal pulmonary
      hypertension.

PMID- 9575873
TI  - Hypoxic exposure time dependently modulates endothelin-induced contraction of
      pulmonary artery smooth muscle.
AB  - Endothelins (ETs) have been implicated in the pathogenesis of hypoxia-induced
      pulmonary hypertension. We determined whether hypoxic exposure of rats (10% O2
      90% N2, 1 atm, 1-48 days) altered contraction to ET in isolated segments of
      endothelium-denuded extralobar branch pulmonary artery (PA) and aorta. Hypoxic
      exposure increased hematocrit, right ventricular hypertrophy, and ET-1 plasma
      concentration. Hypoxia also caused a sustained decrease in PA but not in aorta
      sensitivity to ET-1. In comparison, hypoxic exposure throughout 12 days decreased
      time dependently the maximum contraction of PA to ET-1, BaCl2, and KCl. The
      hypoxia-induced decrease in maximum contraction of PA to ET-1 returned toward
      normal levels by 21 days and approximated control levels by 48 days. After 14
      days of hypoxia, right ventricular hypertrophy correlated with decreased
      sensitivity of PA to ET-1. After 21 days of hypoxia, PA sensitivity to ET-2 and
      ET-3 was decreased, and sarafotoxin S6c-induced contraction was abolished. In
      conclusion, hypoxic exposure time dependently modulates the responsiveness of PA
      smooth muscle to ETs, BaCl2, and KCl. The hypoxia-induced changes in tissue
      responsiveness to ET-1 may be associated with increased plasma concentrations of
      this peptide.

PMID- 9575872
TI  - Effect of tyrosine kinase inhibition on surfactant protein A gene expression
      during human lung development.
AB  - Epidermal growth factor (EGF) stimulates surfactant protein (SP) A synthesis in
      human fetal lung explants. Ligand binding to the EGF receptor stimulates an
      intrinsic receptor tyrosine kinase with subsequent activation of second
      messengers. We hypothesized that inhibition of EGF-receptor tyrosine kinase
      activity would block SP-A expression in spontaneously differentiating cultured
      human fetal lung tissue. Midtrimester fetal lung explants were exposed for 4 days
      to genistein (a broad-range inhibitor of tyrosine kinases) and tyrphostin AG-1478
      (a specific inhibitor of EGF-receptor tyrosine kinase). Genistein significantly
      decreased SP-A and SP-A mRNA levels without affecting either tissue viability or
      the morphological differentiation of alveolar type II cells. Tyrphostin AG-1478
      also decreased SP-A content and SP-A mRNA levels in cultured fetal lung explants.
      Treatment with EGF could not overcome the inhibitory effects of either genistein
      or tyrphostin on SP-A; however, only tyrphostin inhibited EGF-receptor tyrosine
      phosphorylation. We conclude that specific inhibition of EGF-receptor tyrosine
      kinase with tyrphostin AG-1478 blocks the expression of SP-A during spontaneous
      differentiation of cultured human fetal lung tissue. Furthermore, exposure to
      genistein also decreases SP-A expression and blocks the effects of EGF in human
      fetal lung tissue without inhibiting EGF-receptor tyrosine phosphorylation. These
      findings support the importance of tyrosine kinase-dependent signal transduction
      pathways in the regulation of SP-A during human fetal lung development.

PMID- 9575874
TI  - Mechanism of all trans-retinoic acid and glucocorticoid regulation of surfactant
      protein mRNA.
AB  - The surfactant proteins (SPs) are required for the normal function of pulmonary
      surfactant, a lipoprotein substance that prevents alveolar collapse at end
      expiration. We characterized the effects of cortisol and all trans-retinoic acid
      (RA) on SP-A and SP-B gene expression in H441 cells, a human pulmonary
      adenocarcinoma cell line. Cortisol, at 10(-6) M, caused a significant inhibition
      of SP-A mRNA to levels that were 60-70% of controls and a five- to sixfold
      increase in the levels of SP-B mRNA. RA alone (10(-6) M) had no effect on SP-A
      mRNA levels and modestly reduced the inhibitory effect of cortisol. RA alone and
      the combination of cortisol and RA both significantly increased SP-B mRNA levels.
      RA had no effect on the rate of SP-A gene transcription or on SP-A mRNA
      stability. Cortisol alone and the combination of cortisol and RA significantly
      inhibited the rate of SP-A gene transcription but had no effect on SP-A mRNA half
      life. RA at 10(-6) M had no effect on the rate of SP-B gene transcription but
      prolonged SP-B mRNA half-life. Cortisol alone and the combination of cortisol and
      RA caused a significant increase in the rate of SP-B gene transcription and also
      caused a significant increase in SP-B mRNA stability. We conclude that RA has no
      effect on SP-A gene expression and increases SP-B mRNA levels by an effect on SP
      B mRNA stability and not on the rate of SP-B gene transcription. In addition, the
      effects of the combination of RA and cortisol were generally similar to those of
      cortisol alone.

PMID- 9575876
TI  - Acrolein-induced MUC5ac expression in rat airways.
AB  - Acrolein, a low-molecular-weight aldehyde found in photochemical smog and tobacco
      smoke, can induce mucus hypersecretion, inflammation, and airway hyperreactivity.
      To determine whether changes in steady-state mucin gene expression (MUC2 and
      MUC5ac) are associated with histological signs of mucus hypersecretion, rats were
      exposed to acrolein (3.0 parts/million, 6 h/day, 5 days/wk, 2 wk), and the
      trachea with the main stem bronchi was separated from the intrapulmonary airways
      (lung). The temporal expression of MUC2 and MUC5ac mRNA was determined by RT-PCR,
      and acidic mucin glycoproteins were detected by Alcian blue histochemical
      analysis. MUC5ac protein content in the airways was determined by
      immunohistochemical analysis. Tracheal MUC5ac mRNA increased within 2 days and
      was accompanied by an increase in MUC5ac immunostaining on the surface of the
      airways and in submucosal gland epithelium. By comparison, increases in lung
      MUC5ac mRNA and mucin glycoproteins were delayed and were elevated after
      exposures on days 5 and 9, respectively. Increased MUC5ac immunostaining was
      detected within the lumen and airway epithelium of the lung on day 12. In
      contrast, MUC2 mRNA levels were not significantly changed in the trachea or lung.
      These findings indicate that acrolein-induced mucus hypersecretion is due, in
      part, to increases in MUC5ac rather than to MUC2 gene expression. These findings
      suggest that aldehyde-induced increases in MUC5ac may play a role in chronic
      mucus hypersecretion, a pathognomonic feature of chronic obstructive pulmonary
      disease.

PMID- 9575875
TI  - G protein-coupled prostaglandin receptor modulates conductive Na+ uptake in lung
      apical membrane vesicles.
AB  - Because G protein-regulated cation channels in type II pneumocytes constitute the
      most likely pathway for alveolar Na+ entry, we explored the hypothesis that a G
      protein-coupled prostaglandin (PG) E2 receptor controls perinatal lung alveolar
      Na+ transport. [3H]PGE2 binding to the alveolar apical membrane was trypsin
      sensitive and showed a rank order of competitive inhibition: PGE2 = PGE1 > PGD2 >
      PGF2 alpha. Kinetic analysis demonstrated both high-affinity [dissociation
      constant (KD) = 2.1 +/- 0.7 nM; maximal binding (Bmax) = 27 +/- 7 fmol/mg
      protein] and low-affinity (KD = 28 +/- 2 nM; Bmax = 265 +/- 29 fmol/mg protein)
      binding sites. Modulation of high-affinity GTPase activity identified a similar
      potency order (IC50 = 11 mM for PGF2 alpha vs. 10-50 microM for other PGs),
      suggesting that the receptors are G protein coupled. Finally, 1 microM PGE2
      (approximately IC25) increased conductive 22Na+ uptake into membrane vesicles
      only in the presence of 100 microM intravesicular GTP. The KD value for the high
      affinity binding site together with the rank order of PG effect on ligand binding
      and G protein function places this PG receptor in the EP3 subtype, whereas Na+
      uptake studies suggest that it helps maintain perinatal lung Na+ homeostasis.

PMID- 9575877
TI  - Lung-specific induction of heme oxygenase-1 and hyperoxic lung injury.
AB  - Heme oxygenase (HO)-1, which catalyzes heme breakdown, is induced by oxidative
      stress and may protect against oxidative injury. We hypothesized that induction
      of HO-1 by hemoglobin (Hb) in the lung would protect the rat from pulmonary O2
      toxicity. Rats given intratracheal (i.t.) Hb showed lung-specific induction of HO
      1 by 8 h by Western analysis. Rats were then pretreated for 8 h before 60 h of
      exposure to 100% O2 with either IT normal saline, HB, or Hb plus the HO-1
      inhibitor tinprotoporphyrin (SnPP). Both the Hb + O2 and Hb + O2 + SnPP animals
      had less lung injury than normal saline controls as indicated by lower pleural
      fluid volumes and wet-to-dry weight ratios (P < 0.01). The improvement in injury
      in the two Hb-treated groups was the same despite a 61% decrease in HO enzyme
      activity in the Hb + SnPP group after 60 h of O2. In addition, inhibition of HO
      activity with SnPP alone before O2 exposure did not augment the extent of
      hyperoxic lung injury. These results demonstrate that IT Hb induces lung HO-1 in
      the rat and protects against hyperoxia; however, the protection is not mediated
      by increased HO enzyme activity.

PMID- 9575878
TI  - Cigarette smoke extract inhibits fibroblast-mediated collagen gel contraction.
AB  - Cigarette smoking, the major cause of pulmonary emphysema, is characterized by
      destruction of alveolar walls. Because tissue destruction represents a balance
      between injury and repair, we hypothesized that cigarette smoke exposure may
      contribute to the development of emphysema through the inhibition of tissue
      contraction during the repair process. To partially evaluate this hypothesis, we
      investigated the effects of cigarette smoke extract (CSE) on the ability of
      cultured fibroblasts to mediate collagen gel contraction in vitro: CSE inhibited
      fibroblast-mediated gel contraction in a concentration-dependent manner (P <
      0.01). Production of prostaglandin E2, a known inhibitor of fibroblast
      contraction, was unchanged by CSE as was cell surface integrin expression. In
      contrast, fibronectin production by fibroblasts was inhibited (P < 0.01), and
      addition of exogenous fibronectin partially restored the contractile activity,
      thus suggesting at least one mechanism to explain inhibition of gel contraction
      by CSE. When CSE was treated to remove volatile components, it showed less
      inhibitory activity on fibroblast-mediated gel contraction. Therefore, we also
      examined the effects of acrolein and acetaldehyde, two volatile components of
      cigarette smoke. Inhibition of contraction was observed at 5 microM acrolein and
      at 0.5 mM acetaldehyde. In conclusion, cigarette smoke inhibited fibroblast
      mediated gel contraction, and this inhibition was due, at least in part, to the
      volatile components of cigarette smoke and may be mediated, at least in part, by
      a decrease in fibroblast fibronectin production. By inhibition of repair, these
      smoke components may contribute to the development of pulmonary emphysema.

PMID- 9575879
TI  - Cell-specific expression of fibronectin and EIIIA and EIIIB splice variants after
      oxygen injury.
AB  - Cellular fibronectin (cFN) expression is characteristic of injured tissues.
      Unlike plasma FN, cFN mRNA often contains the EIIIA or EIIIB domains. We examined
      the lung cell-specific expression of total cFN mRNA and the EIIIA and EIIIB
      splice variants in rabbits after acute oxygen injury. By in situ hybridization,
      control lung had low cFN mRNA. After exposure to > 95% oxygen, mRNAs for total
      cFN and EIIIA were noted primarily in alveolar macrophages and large-vessel
      endothelial cells. By 3-5 days recovery, cFN and EIIIA mRNA abundance was
      increased in alveolar septal cells (i.e., alveolar epithelial, interstitial, or
      endothelial cells) and in some large-vessel endothelial cells but was low in
      bronchial epithelial cells. During recovery, EIIIB mRNA was low in alveolar
      septal cells but was noted mainly in chondrocytes. Immunostaining for EIIIA
      increased during recovery, paralleling the in situ hybridizations. Because FN may
      modulate alveolar type II cell phenotype, we investigated type II cell cFN mRNA
      expression in vivo. During recovery, neither isolated type II cells nor cells
      with surfactant protein C mRNA in vivo contained FN mRNA. In summary, these data
      suggest that cFN with the EIIIA domain has a role in alveolar cell recovery from
      oxygen injury and that type II cells do not express cFN during recovery.

PMID- 9575880
TI  - Growth factors and dexamethasone regulate Hoxb5 protein in cultured murine fetal
      lungs.
AB  - Studies on lung morphogenesis have indicated a role of homeobox (Hox) genes in
      the regulation of lung development. In the present study, we attempted to
      modulate the synthesis of Hoxb5 protein in cultured murine fetal lungs after
      mechanical or chemical stimuli. Murine fetuses at gestational day 14 (GD14) were
      removed from pregnant CD-1 mice, and lungs were excised and cultured for 7 days
      in BGJb media. The experimental groups were 1) untreated, unligated; 2) tracheal
      ligation; 3) supplemented media with either epidermal growth factor (EGF; 10
      ng/ml), transforming growth factor (TGF)-beta 1 (2 ng/ml), dexamethasone (10 nM),
      EGF + TGF-beta 1, or EGF + TGF-beta 1 + dexamethasone. After 3 or 7 days, the
      cultured lungs were compared with in vivo lungs. Immunoblotting signals at 3 days
      in culture were stronger than those at 7 days. Western blot analyses showed that
      ligation, EGF, TGF-beta 1, and EGF + TGF-beta 1 downregulated Hoxb5 protein to
      approximately 20-70% of Hoxb5 protein levels in unligated, untreated cultured
      lungs. Furthermore, dexamethasone alone or in combination with EGF and TGF-beta 1
      downregulated Hoxb5 protein by > 90% (P < 0.05) signal strength, similar to that
      seen in GD19 or in neonatal lungs. Immunostaining showed that Hoxb5 protein was
      expressed strongly in the lung mesenchyme at early stages in gestation. However,
      by GD19 and in neonates, it was present only in specific epithelial cells. A
      persistent level of Hoxb5 protein in the mesenchyme after EGF or TGF-beta 1
      treatments or tracheal ligation was noted. Hoxb5 protein was significantly
      downregulated by EGF + TGF-beta 1, and it was least in lungs after dexamethasone
      or EGF + TGF-beta 1 + dexamethasone treatment. The decrease in Hoxb5 protein was
      significant only in the groups with dexamethasone added to the media. Thus
      immunostaining results parallel those of immunoblotting. The degree of Hoxb5
      downregulation by dexamethasone or EGF + TGF-beta 1 + dexamethasone was similar
      to that seen in vivo in very late gestation, which correlated to the advancing
      structural development of the lung.

PMID- 9575881
TI  - Molecular basis and function of voltage-gated K+ channels in pulmonary arterial
      smooth muscle cells.
AB  - K(+)-channel activity-mediated alteration of the membrane potential and
      cytoplasmic free Ca2+ concentration ([Ca2+]cyt) is a pivotal mechanism in
      controlling pulmonary vasomotor tone. By using combined approaches of patch
      clamp, imaging fluorescent microscopy, and molecular biology, we examined the
      electrophysiological properties of K+ channels and the role of different K+
      currents in regulating [Ca2+]cyt and explored the molecular identification of
      voltage-gated K+ (KV)- and Ca(2+)-activated K+ (KCa)-channel genes expressed in
      pulmonary arterial smooth muscle cells (PASMC). Two kinetically distinct KV
      currents [IK(V)], a rapidly inactivating (A-type) and a noninactivating delayed
      rectifier, as well as a slowly activated KCa current [IK(Ca)] were identified.
      IK(V) was reversibly inhibited by 4-aminopyridine (5 mM), whereas IK(Ca) was
      significantly inhibited by charybdotoxin (10-20 nM). K+ channels are composed of
      pore-forming alpha-subunits and auxiliary beta-subunits. Five KV-channel alpha
      subunit genes from the Shaker subfamily (KV1.1, KV1.2, KV1.4, KV1.5, and KV1.6),
      a KV-channel alpha-subunit gene from the Shab subfamily (KV2.1), a KV-channel
      modulatory alpha-subunit (KV9.3), and a KCa-channel alpha-subunit gene (rSlo), as
      well as three KV-channel beta-subunit genes (KV beta 1.1, KV beta 2, and KV beta
      3) are expressed in PASMC. The data suggest that 1) native K+ channels in PASMC
      are encoded by multiple genes; 2) the delayed rectifier IK(V) may be generated by
      the KV1.1, KV1.2, KV1.5, KV1.6, KV2.1, and/or KV2.1/KV9.3 channels; 3) the A-type
      IK(V) may be generated by the KV1.4 channel and/or the delayed rectifier KV
      channels (KV1 subfamily) associated with beta-subunits; and 4) the IK(Ca) may be
      generated by the rSlo gene product. The function of the KV channels plays an
      important role in the regulation of membrane potential and [Ca2+]cyt in PASMC.

PMID- 9575882
TI  - Inhibition of vascular and epithelial differentiation in murine nitrofen-induced
      diaphragmatic hernia.
AB  - Neonates with congenital diaphragmatic hernia (DH) die of pulmonary hypoplasia
      and persistent pulmonary hypertension. We used immunohistochemical localization
      of alpha-smooth muscle actin (alpha-SMA), platelet endothelial cell adhesion
      molecule (PECAM)-1, thyroid transcription factor (TTF)-1, surfactant protein (SP)
      A, SP-C, and competitive RT-PCR quantitation of TTF-1, SP-A, SP-C, and alpha-SMA
      mRNA expression to characterize the epithelial and vascular phenotype of lungs
      from ICR fetal mice with a nitrofen-induced DH. Nitrofen (25 mg) was gavage fed
      to pregnant mice on day 8 of gestation. Fetal mice were delivered on day 17. The
      diaphragm was examined for a defect, and the lungs were either fixed, sectioned,
      and immunostained or processed for mRNA isolation. In comparison with control
      lungs, DH lungs showed increased expression of alpha-SMA mRNA, fewer and more
      muscular arterioles (alpha-SMA), less well-developed capillary networks (PECAM
      1), delayed epithelial development marked by a persistence of TTF-1 in the
      periphery, and decreased SP-A mRNA and SP-A expression. These data suggest that
      in the murine nitrofen-induced DH, as in human congenital DH, pulmonary
      insufficiency is due to an inhibition of peripheral pulmonary development
      including terminal airway and vascular morphogenesis.

PMID- 9575883
TI  - Insulin-like growth factor binding proteins in air- and 85% oxygen-exposed adult
      rat lung.
AB  - Expression of insulin-like growth factor (IGF) I and its type I receptor is
      increased in the adult rat lung exposed to 85% O2. We hypothesized that there
      would be a parallel up- and downregulation of growth-stimulating and growth
      inhibiting IGF binding proteins (IGFBPs), respectively. The normal adult rat lung
      expresses mRNAs for IGFBP-2, -3, -4, -5, and -6 but not for IGFBP-1. O2 exposure
      for 6 or 14 days reduced IGFBP-3 and -6 and increased IGFBP-4 mRNA abundance.
      IGFBP-5 mRNA was reduced at 6 days but increased at 14 days. IGFBP-4 mRNA was
      localized to perivascular and peribronchial interstitial cells and IGFBP-5 mRNA
      to airway and alveolar epithelial cells. IGFBP-2, -4, and -5 immunolocalized to
      airway epithelial cells in normal lung and to perivascular exudates after 6 days
      in 85% O2. IGFBP-2 was diffusely increased throughout the lung tissue only after
      a 6-day exposure. IGFBP-5 was reduced after a 6-day exposure but was increased
      and widely distributed after 14 days. IGFBP-4 increased over airway epithelium
      and subepithelial cells after 6 days and over perivascular interstitial cells
      after 14 days of 85% O2. These data are consistent with the predicted changes for
      IGFBPs on O2 exposure except that the generally growth-inhibitory IGFBP-4 was
      increased at sites of active cell proliferation.

PMID- 9575884
TI  - Hypoxic pulmonary endothelial cells release a diffusible contractile factor
      distinct from endothelin.
AB  - Hypoxia (0% O2) evokes a late-phase, endothelium-dependent contractile response
      in porcine isolated pulmonary arteries that may be caused by a cyclooxygenase
      independent, endothelium-derived contractile factor. The aim of this study was to
      further analyze the mechanism underlying this hypoxic response. Proximal porcine
      pulmonary arterial rings were suspended for isometric tension recording in organ
      chambers. Hypoxia (0% O2) caused a late-phase, endothelium-dependent contractile
      response that was not inhibited by the endothelin (ET)A-receptor antagonist BQ
      123 (10(-6) M), by the ETB-receptor antagonist BQ-788 (10(-7) M), or by their
      combination. In contrast, ET-1 caused a concentration-dependent contraction of
      arterial rings that was inhibited by BQ-123 (10(-6) M) and a relaxation that was
      abolished by BQ-788 (10(-7) M) or by endothelial cell removal. Therefore, the
      endothelium-dependent contraction to hypoxia is not mediated by ET. Hypoxia
      caused only relaxation in endothelium-denuded rings. However, when a pulmonary
      valve leaflet, a rich source of pulmonary endothelial cells, was placed into the
      lumen of endothelium-denuded rings, hypoxia caused a late-phase contractile
      response that was similar to that observed in arterial rings with native
      endothelium. This hypoxic contraction persisted in the presence of indomethacin
      (10(-5) M) and N-nitro-L-arginine methyl ester (3 x 10(-5) M) to block
      cyclooxygenase and nitric oxide synthase, respectively. These results suggest
      that hypoxic contraction of pulmonary arteries is mediated by a diffusible,
      contractile factor released from hypoxic endothelial cells. This contractile
      mediator is distinct from ET.

PMID- 9575885
TI  - Dietary salt modulates renal production of transforming growth factor-beta in
      rats.
AB  - Transforming growth factors (TGF) are potent multifunctional polypeptides that
      are involved in renal function and glomerular sclerosis. We postulated that
      dietary salt modified renal production of TGF-beta. An increase in dietary salt
      produced sustained increases in steady-state levels of mRNA for TGF-beta 1, -beta
      2, and -beta 3 in the rat kidney. While serum concentration of TGF-beta 1 did not
      change, the 8.0% NaCl diet increased urinary excretion of TGF-beta 1, indicating
      enhanced renal production was the source of TGF-beta 1. Increasing urinary flow
      rates with diuretics did not further increase synthesis of TGF-beta 1 in animals
      receiving the 8.0% NaCl diet. The 8.0% NaCl diet increased production of TGF-beta
      1 in both glomeruli and tubules, although active TGF-beta 1 was secreted in
      greater amounts only from glomeruli. Enhanced glomerular production of both
      inactive and active TGF-beta 1 induced by the 8.0% NaCl diet was inhibited by
      tetraethylammonium (TEA) and not glybenclamide. Cardiac production of TGF-beta 1
      also increased on the 8.0% NaCl diet but was not affected by TEA. The results
      demonstrated that increased dietary salt augmented glomerular TGF-beta production
      by a mechanism that included a TEA-sensitive potassium channel. Dietary salt, by
      facilitating glomerular expression of TGF-beta, may directly promote development
      of glomerulosclerosis.

PMID- 9575887
TI  - Effect of growth hormone on renal and systemic acid-base homeostasis in humans.
AB  - The effects of recombinant human growth hormone (GH, 0.1 U.kg body wt-1.12 h-1)
      on systemic and renal acid-base homeostasis were investigated in six normal
      subjects with preexisting sustained chronic metabolic acidosis, induced by NH4Cl
      administration (4.2 mmol.kg body wt-1.day-1). GH administration increased and
      maintained plasma bicarbonate concentration from 14.1 +/- 1.4 to 18.6 +/- 1.1
      mmol/l (P < 0.001). The GH-induced increase in plasma bicarbonate concentration
      was the consequence of a significant increase in net acid excretion that was
      accounted for largely by an increase in renal NH+4 excretion sufficient in
      magnitude to override a decrease in urinary titratable acid excretion. During GH
      administration, urinary pH increased and correlated directly and significantly
      with urinary NH4+ concentration. Urinary net acid excretion rates were not
      different during the steady-state periods of acidosis and acidosis with GH
      administration. Glucocorticoid and mineralocorticoid activities increased
      significantly in response to acidosis and were suppressed (glucocorticoid) or
      decreased to control levels (mineralocorticoid) by GH. The partial correction of
      metabolic acidosis occurred despite GH-induced renal sodium retention (180 mmol;
      gain in weight of 1.8 +/- 0.2 kg, P < 0.005) and decreased glucocorticoid and
      mineralocorticoid activities. Thus GH (and/or insulin-like growth factor I)
      increased plasma bicarbonate concentration and partially corrected metabolic
      acidosis. This effect was generated in large part by and maintained fully by a
      renal mechanism (i.e., increased renal NH3 production and NH+4/net acid
      excretion).

PMID- 9575886
TI  - Downregulation of nitric oxide synthase in chronic renal insufficiency: role of
      excess PTH.
AB  - The available data on the effect of chronic renal failure (CRF) on nitric oxide
      (NO) metabolism are limited and contradictory. We studied rats with CRF 6 wk
      after a five-sixths nephrectomy and compared the results with those in the sham
      operated controls, felodipine-treated CRF, and parathyroidectomized (CRF-PTX)
      animals. CRF was produced by surgical resection of the upper and lower thirds of
      the left kidney, followed by contralateral nephrectomy. We chose this model, as
      opposed to that produced by renal artery branch ligation, because the latter
      causes exuberant hypertension (HTN), which independently affects NO metabolism.
      The CRF group exhibited a mild HTN coupled with elevated basal platelet cytosolic
      Ca2+ concentration ([Ca2+]i), blunted hypotensive response to L-arginine,
      decreased hypertensive response to NO synthase (NOS) inhibitor, NG-monomethyl-L
      arginine, and normal hypotensive response to NO donor, sodium nitroprusside. This
      was associated with a significant reduction in urinary excretion of stable NO
      metabolites (NOX) and depressed NOS activity, as well as endothelial and
      inducible NO synthase (eNOS and iNOS, respectively) protein contents of thoracic
      aorta and the remnant kidney in the CRF animals. Calcium channel blockade and PTX
      lowered blood pressure, increased urinary NOX, and enhanced vascular NOS
      activity, as well as eNOS and iNOS protein expressions in the tested tissues.
      Thus CRF animals exhibited significant reductions in vascular NOS activity and
      eNOS and iNOS expressions. These abnormalities were reversed by calcium channel
      blockade and PTX, suggesting the possible causal role of CRF-induced
      dysregulation of [Ca2+]i.

PMID- 9575888
TI  - Arachidonic acid potentiates the feedback response of mesangial BKCa channels to
      angiotensin II.
AB  - The influence of arachidonic acid (AA) on the feedback regulation of mesangial
      contraction by large Ca(2+)-activated K+ channels (BKCa) was determined through
      single-channel analysis using the patch clamp method. The mesangial BKCa is a low
      gain negative feedback inhibitor of contraction that is activated in response to
      agonist-induced Ca2+ transients and membrane depolarization. AA activated BKCa in
      cell-attached patches in a dose-dependent manner with a maximal effect at 400 nM
      and a half-maximal response at 49 nM. In inside-out patches, AA directly
      activated BKCa with a maximal effect at 400 nM. BKCa was activated significantly
      in response to addition of 100 nM ANG II in the presence but not the absence of
      AA. Since it was shown previously that fatty acids stimulated both soluble and
      membrane-bound guanylyl cyclase, we determined whether AA activated BKCa by
      interfering with cGMP-mediated signal transduction pathways. It was previously
      shown that 10 microM cGMP, via cGMP-dependent protein kinase, activated BKCa in a
      biphasic manner with an early increase in probability of a channel existing in an
      open state (Po) and a subsequent inactivation mediated by protein phosphatase 2A
      (PP2A). We found that 10 microM dibutyryl-cGMP enhanced BKCa activity in an
      additive manner with saturating concentrations (400 nM) of AA. Moreover, the
      inactivation phase mediated by PP2A was not abolished. Thus AA does not affect
      the phosphorylation/dephosphorylation regulatory cycle for BKCa. It is concluded
      that AA potentiates the ANG II feedback response of BKCa by a mechanism that is
      independent of the phosphorylation cycle.

PMID- 9575889
TI  - K depletion stimulates in vivo HCO3 reabsorption in surviving rat distal tubules.
AB  - To evaluate whether K depletion enhances in vivo bicarbonate reabsorption (JtCO2)
      in surviving distal tubules (DT), we compared DT JtCO2 in five-sixths
      nephrectomized rats (Nx) with and without dietary K depletion (Nx-K).
      Furthermore, to identify possible mechanisms of increased JtCO2, we perfused
      inhibitors of proton secretion in both Nx and Nx-K rats. JtCO2 (102 +/- 8
      pmol.min-1.mm-1) was significantly increased in Nx-K vs. Nx rats (65 +/- 7
      pmol.min-1.mm-1, P < 0.05) but unaffected by 10(-6) M losartan perfusion (94 +/-
      6 pmol.min-1.mm-1, P = not significant). Although 10(-5) M Sch-28080 also had no
      significant effect, 5 x 10(-9) M concanamycin A perfusion significantly decreased
      JtCO2 in Nx-K rats to 65 +/- 8 pmol.min-1. mm-1 (P < 0.05). Morphometric
      evaluation and H(+)-ATPase immunogold labeling of Nx-K A-type intercalated cells
      revealed cellular hypertrophy, elaborated apical microplicae, and enhanced H(+)
      ATPase apical polarization. Accordingly, these combined studies confirm that K
      depletion enhances JtCO2 in surviving DT by stimulating H(+)-ATPase activity,
      independent of the AT1 receptor.

PMID- 9575890
TI  - IGF-I and insulin amplify IL-1 beta-induced nitric oxide and prostaglandin
      biosynthesis.
AB  - The inflammatory cytokine interleukin-1 beta (IL-1 beta) induces both
      cyclooxygenase-2 (Cox-2) and the inducible nitric oxide synthase (iNOS) with
      concomitant release of PGs and nitric oxide (NO) by glomerular mesangial cells.
      In our current studies, we determine whether insulin and IGF-I are involved in
      the signal transduction mechanisms resulting in IL-1 beta-induced NO and PGE2
      biosynthesis in renal mesangial cells. We demonstrate that both insulin and IGF-I
      increase IL-1 beta-induced Cox-2 and iNOS protein expression, which in turn
      enhance PGE2 and NO production. Our data also indicate that both insulin and IGF
      I enhance IL-1 beta-induced p38 mitogen-activated protein kinase (MAPK)
      phosphorylation and SAPK activation. These findings implicate the possible role
      of the MAPK pathway in mediating the effects of insulin and IGF-I on the
      upregulation of cytokine-stimulated NO and PG biosynthesis. Together, our results
      indicate that IGF-I and insulin may function to modulate the renal inflammatory
      process.

PMID- 9575891
TI  - Blood pressure variability and urine flow in the conscious dog.
AB  - Pressure-dependent urine production is considered to be a major factor in long
      term blood pressure control. The phenomenon has been well characterized for fixed
      levels of renal perfusion pressure (RPP), but the influence of physiological
      fluctuations in RPP and spontaneous variations in renal blood flow (RBF) on short
      term urine flow (UV) remain unclear. To clarify this issue, we studied the
      interdependence of RPP, RBF, and UV in 13 conscious foxhounds during a single
      step pressure reduction, under normal conditions, and with induced pressure
      changes. Reducing RPP in a single step to approximately 80 mmHg revealed short
      response times of RBF (0.4 +/- 0.1 s, n = 7) as well as of UV (8.1 +/- 0.8 s, n =
      7). Under control conditions, UV was coupled with spontaneous variations of RBF
      (r = 0.94, P < 0.001), in contrast to RPP, which showed no significant
      correlation with UV (r = 0.09, P = NS). To discern the pressure and blood flow
      dependency of UV at a reduced RPP, we induced 0.9-mHz blood pressure oscillations
      (80 +/- 10 mmHg), which phase shifted RPP and RBF. Conversely, under these
      conditions, UV was dependent on RPP (r = 0.95, P < 0.001). These results suggest
      that spontaneous fluctuations in RBF around a normal baseline level lead to
      concomitant changes in urine production, in contrast to physiological short-term
      oscillations in RPP, which are not correlated to changes in UV. However, during
      induced oscillations of perfusion pressure, the blood flow dependence was no
      longer observed and UV was entirely pressure dependent.

PMID- 9575893
TI  - A decrease in renal medullary tonicity stimulates anion transport in Henle's loop
      of rat kidneys.
AB  - To investigate the effect of reduction in renal medulla osmolality on loop of
      Henle (LOH) net bicarbonate reabsorption, clearance and microperfusion
      experiments were performed on Sprague-Dawley rats. The decrease of renal medulla
      osmolality was induced by intravenous infusion of either a large dose of mannitol
      (mannitol protocol) or a hypotonic solution (hypotonic protocol) delivered at a
      rate to match the sodium and bicarbonate load of the control period. During the
      mannitol protocol, clearance data demonstrated a rise in glomerular filtration
      rate (GFR), renal plasma flow, urine pH, and fractional bicarbonate excretion. On
      the contrary, microperfusion experiments, performed in the absence of mannitol in
      the tubular perfusate, revealed a significant increase both in the absolute and
      fractional LOH bicarbonate transport. During the hypotonic protocol, there was a
      decrease in GFR, associated with an increase in fractional excretion of
      bicarbonate. In the microperfusion experiments, hypotonic saline, similar to
      mannitol, stimulated absolute and fractional LOH bicarbonate transport. Net
      reabsorption of chloride, measured under the same experimental conditions, was
      also found to be activated. Therefore, the intravenous infusion of hypotonic
      solution affected the LOH transepithelial net reabsorption of both bicarbonate
      and chloride. We hypothesize that the increase in the transport rate of these two
      anions, along the same segment and in similar experimental conditions, may be
      mediated, at least in part, by decreased medullary tonicity, which is one factor
      common both to hypertonic mannitol and hypotonic saline infusion.

PMID- 9575892
TI  - K+ depletion increases HCO3- reabsorption in OMCD by activation of colonic H(+)
      K(+)-ATPase.
AB  - To probe the role of the isoforms of H(+)-K(+)-ATPase (HKA) in potassium
      depletion (KD), rats were placed on a KD diet for 2 wk. Colonic HKA (cHKA) mRNA
      levels increased approximately 30-fold in outer medulla, and net HCO3-flux
      (JtCO2) in outer medullary collecting duct (OMCD) increased (13.1 pmol.min-1.mm
      tubule length-1 in control to 17.7 pmol.min-1.mm tubule length-1 in KD; P <
      0.01). In normal rats, 1 mM ouabain in perfusate had no effect on JtCO2, whereas
      10 microM Sch-28080 decreased JtCO2 to 5.1 pmol.min-1.mm tubule length-1 (P <
      0.001). In KD rats, ouabain 1 mM decreased JtCO2 to 6.3 pmol.min-1.mm tubule
      length-1 (P < 0.001). Although 10 microM Sch-28080 also decreased JtCO2 to 4.6
      pmol.min-1.mm tubule length-1 (P < 0.001), the inhibitory effects of Sch-28080
      and ouabain were not additive. Removal of K+ from perfusate blocked Sch-28080
      sensitive JtCO2 in both normal and KD tubules. The data suggest that, in KD, cHKA
      is induced and mediates increased HCO3-reabsorption in OMCD, cHKA in vivo is
      sensitive to both Sch-28080 and ouabain, and cHKA activity is dominant.

PMID- 9575894
TI  - Anomalous decrease in dextran sulfate clearance in the diabetic rat kidney.
AB  - The anomalous increase in charge selectivity as previously observed with reduced
      dextran sulfate clearances in diabetic rats (L. D. Michels, M. Davidman, and W.
      F. Keane. Kidney Int. 21: 699-705, 1982) was confirmed in 4-wk streptozotocin
      (STZ) diabetic Sprague-Dawley rats using the isolated perfused kidney technique.
      The apparent charge selectivity in both control and diabetic rats could be
      abolished by increasing the dextran sulfate concentration to 200 micrograms/ml in
      the perfusate. This was demonstrated by a high rate of processing of dextran
      sulfate (approximately 1,700 ng.min-1.kidney-1) by glomeruli in both control and
      diabetic kidneys and by the fact that charge interaction could not explain the
      concentration dependence. The amount of urinary desulfation of dextran sulfate
      was also found to be significantly less in the diabetic kidney as was glomerular
      sulfatase activity compared with controls. Dextran sulfate glomerular processing
      is therefore altered in the STZ diabetic rat kidney but could be rationalized in
      terms of previous models of endothelial cell receptor-mediated uptake of dextran
      sulfate. The results are consistent with recent work demonstrating that there is
      little or no electrostatic charge interaction operating on dextran sulfate or
      other negatively charged molecules at the glomerular capillary wall.

PMID- 9575895
TI  - Stimulation of renin secretion by NO donors is related to the cAMP pathway.
AB  - This study aimed to characterize the cellular pathways along which nitric oxide
      (NO) influences the secretion of renin from the kidney. Using the isolated
      perfused rat kidney model, we found that the NO donor sodium nitroprusside (SNP)
      (1-30 mumol/l) induced a prompt, concentration-dependent fourfold increase of
      basal renin secretion. The membrane-permeable cGMP analogs 8-bromo-cGMP and 8-(4
      chlorophenylthio)-cGMP (8-pCPT-cGMP; each 5-50 mumol/l) inhibited basal renin
      secretion and attenuated the stimulation of renin secretion by SNP. Conversely,
      the renin stimulatory effect of SNP was enhanced in the presence of the G kinase
      inhibitor Rp-8-CPT-cGMPS (10 mumol/l). The renin stimulatory effect of SNP was
      amplified in nominally calcium-free perfusate and was abolished in the presence
      of angiotensin II (1 nmol/l). Renin secretion stimulated by SNP was clearly
      attenuated by the A kinase inhibitor Rp-8-CPT-cAMPS (25 mumol/l). These findings
      indicate that the renin stimulatory effect of NO donors in renal juxtaglomerular
      cells cannot be explained by activation of G kinase and is also less likely to be
      causally related to the regulation of renin secretion by calcium. Because A
      kinase activity is required for the stimulation of renin secretion by SNP, it
      appears as if the renin stimulatory effect is causally related to the cAMP
      pathway controlling renin secretion.

PMID- 9575896
TI  - Direct assessment of renal microvascular responses to P2-purinoceptor agonists.
AB  - Studies were performed to determine the responsiveness of rat juxtamedullary
      afferent arterioles to receptor-selective P2-purinoceptor agonists. Experiments
      were performed in vitro using the blood perfused juxtamedullary nephron
      technique, combined with videomicroscopy. Renal perfusion pressure was set at 110
      mmHg and held constant. Basal afferent arteriolar diameter averaged 22.0 +/- 0.6
      microns (n = 69). Stimulation with 0.1, 1.0, 10, and 100 microM ATP (n = 10)
      elicited a concentration-dependent vasoconstriction averaging 8 +/- 2, 17 +/- 2,
      21 +/- 4, and 23 +/- 5%, respectively. A nearly identical afferent arteriolar
      vasoconstriction was observed in response to the P2X-selective agonist beta,gamma
      methylene ATP (n = 10); however, another P2X agonist, alpha,beta-methylene ATP,
      evoked marked receptor desensitization (n = 10). Vessel diameter decreased by
      approximately 7 +/- 2, 16 +/- 2, 23 +/- 3, and 22 +/- 3%, respectively, over the
      same concentration range. The P2Y-selective agonist, 2-methylthio-ATP, evoked
      only a modest vasoconstriction, whereas UTP and adenosine 5'-O-(3
      thiotriphosphate) (ATP gamma S) reduced afferent diameter markedly at
      concentrations > 1.0 microM. Afferent arteriolar diameter decreased by 5 +/- 4,
      31 +/- 8, and 72 +/- 8% during UTP administration (n = 7) at concentrations of
      1.0, 10, and 100 microM, respectively. Similarly, ATP gamma S (n = 6) decreased
      afferent diameter by 16 +/- 2, 58 +/- 8, and 98 +/- 3%, respectively, over the
      same concentration range. Nitric oxide synthesis inhibition with N omega-nitro-L
      arginine did not significantly alter the afferent arteriolar response to ATP but
      did potentiate ATP-mediated arcuate artery vasoconstriction. The following data
      suggest the presence of multiple P2 receptors on juxtamedullary afferent
      arterioles and are consistent with classification of those receptors as members
      of the P2X- and P2Y2 (P2U)-receptor subtypes.

PMID- 9575897
TI  - A role for PKC epsilon and MAP kinase in bradykinin-induced arachidonic acid
      release in rabbit CCD cells.
AB  - Arachidonic acid (AA) release is the rate-limiting step in the production of
      prostaglandins, an important class of autocrine/paracrine factors that modulate
      collecting duct function. Previous results from this laboratory have established
      cytosolic phospholipase A2 (cPLA2) as the enzyme responsible for bradykinin (BK)
      stimulated AA mobilization in rabbit cortical collecting duct (RCCD) cells, and
      the present study pursues the intracellular signaling mechanisms responsible for
      its activation. Pretreatment of cells with Ro-31-8220, an inhibitor of protein
      kinase C (PKC), or PD-98059, an inhibitor of the mitogen-activated protein kinase
      (MAPK) cascade, resulted in a 50-60% reduction in BK-stimulated AA release.
      Incubation of RCCD cells with a combination of both Ro-31-8220 and PD-98059 did
      not achieve a greater inhibition of either BK-stimulated AA release or cPLA2
      activity, possibly indicating that MAPK activation was dependent upon prior
      activation of PKC. This was supported by the observation that BK-induced MAPK
      activation could be reversed by either inhibitor. Additional experiments dealing
      with immunoblots for PKC isozymes revealed that RCCD cells express PKC species
      alpha, gamma, epsilon, and zeta. Following BK stimulation, only PKC epsilon
      translocated to the particulate fraction. Based on these results, it appears that
      PKC is activated and involved in the sequential activation of MAPK and cPLA2
      following BK treatment. The results also suggest that PKC epsilon may be the
      isozyme implicated in the process.

PMID- 9575898
TI  - Adenosine-stimulated Ca2+ reabsorption is mediated by apical A1 receptors in
      rabbit cortical collecting system.
AB  - Confluent monolayers of immunodissected rabbit connecting tubule and cortical
      collecting duct cells, cultured on permeable supports, were used to study the
      effect of adenosine on net apical-to-basolateral Ca2+ transport. Apical, but not
      basolateral, adenosine increased this transport dose dependently from 48 +/- 3 to
      110 +/- 4 nmol.h-1.cm-2. Although a concomitant increase in cAMP formation
      suggested the involvement of an A2 receptor, the A2 agonist CGS-21680 did not
      stimulate Ca2+ transport, while readily increasing cAMP. By contrast, the A1
      agonist N6-cyclopentyladenosine (CPA) maximally stimulated Ca2+ transport without
      significantly affecting cAMP. Adenosine-stimulated transport was effectively
      inhibited by the A1 antagonist 1,3-dipropyl-8-cyclopenthylxanthine but not the A2
      antagonist 3,7-dimethyl-1-propargylxanthine, providing additional evidence for
      the involvement of an A1 receptor. Both abolishment of the adenosine-induced
      transient increase in intracellular Ca2+ concentration by 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and downregulation of protein
      kinase C (PKC) by prolonged phorbol ester treatment were without effect on
      adenosine-stimulated Ca2+ transport. The data presented suggest that adenosine
      interacts with an apical A1 receptor to stimulate Ca2+ transport via a hitherto
      unknown pathway that does not involve cAMP formation, PKC activation, and/or Ca2+
      mobilization.

PMID- 9575899
TI  - Effect of modifying O2 diffusivity and delivery on glomerular and tubular
      function in hypoxic perfused kidney.
AB  - Is O2 diffusivity within renal capillaries rate limiting for O2 delivery to
      hypoxic renal tubules? Equations based on diffusion theory and developed here
      predict that soluble hemoglobin (Hb) increases O2 diffusivity by a factor of 1 +
      [442 Hb%/(P50 + PO2)], where P50 is the partial pressure of O2 at which the Hb is
      half saturated. To examine the effect of P50 and Hb concentrations on renal
      function, we perfused isolated rat kidneys with Hb-P35 (P50 = 35 mmHg) and Hb-P11
      (P50 = 11 mmHg). Venous PO2 was lower with Hb-P11 (10 +/- 1 vs 16 +/- 1 mmHg with
      arterial PO2 = 35 mmHg and 28 +/- 2 vs. 40 +/- 2 mmHg with arterial PO2 = 140
      mmHg; P < 0.001). Perfusate P50 did not influence vascular resistance, glomerular
      filtration rate, O2 consumption, Na reabsorption, protein excretion, or free
      water clearance. Percent glucose and phosphate excretion were lower with Hb-P11
      than with Hb-P35 (P < 0.001). Urine glucose was 0.17 mmol/l with Hb-P11 and 0.77
      mmol/l with Hb-P35 (P < 0.001). Hb-P35 (2%) doubled O2 delivery and lowered
      glucose and phosphate excretion to the level obtained with 1% Hb-P11. Thus Hb-P11
      delivered O2 twice as effectively as Hb-P35 to high-affinity sodium glucose and
      phosphate cotransporters in the late proximal tubule (S3 segment). Hb-P11 may
      also have shunted O2 from the outer cortex to the outer medulla and facilitated
      O2 diffusion where PO2 was low. We conclude that diffusivity is a limiting factor
      in delivery of O2 to hypoxic tubules.

PMID- 9575900
TI  - Cis- and trans-acting factors regulating transcription of the BGT1 gene in
      response to hypertonicity.
AB  - We have previously identified a tonicity-responsive enhancer (TonE) in the
      promoter region of the canine BGT1 gene. TonE mediates hypertonicity-induced
      stimulation of transcription. Here, we characterize TonE and TonE binding
      proteins (TonEBPs) to provide a biochemical basis for cloning of the TonEBPs.
      Mutational analysis applied to both hypertonicity-induced stimulation of
      transcription and TonEBP binding reveals that TonE is 11 base pairs in length,
      with the consensus sequence of (C/T)GGAAnnn(C/T)n(C/T). Activity of the TonEBPs
      increases in response to hypertonicity with a time course similar to that of
      transcription of the BGT1 gene. Studies with inhibitors indicate that
      translation, but not transcription, is required for activation of the TonEBPs.
      Phosphorylation is required for the stimulation of transcription but not for
      activation of DNA binding by the TonEBPs. In vivo methylation by dimethyl sulfate
      reveals that the TonE site of the BGT1 gene is protected with a time course like
      that of activity of the TonEBPs and activation of transcription. Ultraviolet
      cross-linking indicates that the TonEBPs share a DNA binding subunit of 200 kDa.

PMID- 9575901
TI  - Effects of glycine betaine and glycerophosphocholine on thermal stability of
      ribonuclease.
AB  - Urea in renal medullas is sufficiently high to perturb macromolecules, yet the
      cells survive and function. The counteracting osmolytes hypothesis holds that
      methylamines, such as glycine betaine (betaine) and glycerophosphocholine (GPC)
      in renal medullas, stabilize macromolecules and oppose the effects of urea.
      Although betaine counteracts effects of urea on macromolecules in vitro and
      protects renal cells from urea in tissue culture, renal cells accumulate GPC
      rather than betaine in response to high urea both in vivo and in tissue culture.
      A proposed explanation is that GPC counteracts urea more effectively than
      betaine. However, we previously found GPC slightly less effective than betaine in
      counteracting inhibition of pyruvate kinase activity by urea. To test another
      macromolecule, we now compare GPC and betaine in counteracting reduction of the
      thermal stability of Rnase A by urea. We find that urea decreases the thermal
      transition temperature and that betaine and GPC increase it, counteracting urea
      approximately equally. Therefore, the preference for GPC in response to high urea
      presumably has some other basis, such as a lower metabolic cost of GPC
      accumulation.

PMID- 9575902
TI  - Regulation of intrarenal blood flow in experimental heart failure: role of
      endothelin and nitric oxide.
AB  - Congestive heart failure(CHF) is associated with a marked decrease in cortical
      blood flow and preservation of medullary blood flow. In the present study we
      tested the hypothesis that changes in the endothelin (ET) and nitric oxide (NO)
      systems in the kidney may contribute to the altered intrarenal hemodynamics in
      rats with aortocaval fistula, an experimental model of CHF. Cortical and
      medullary blood flow were measured simultaneously by laser-Doppler flowmetry in
      controls and rats with compensated and decompensated CHF. As previously reported
      [K. Gurbanov, I. Rubinstein, A. Hoffman, Z. Abassi, O. S. Better, and J. Winaver.
      Am. J Physiol. 271 (Renal Fluid Electrolyte Physiol. 40): F1166-F1172, 1996],
      administration of ET-1 in control rats produced a sustained cortical
      vasoconstriction and a transient medullary vasodilatory response. In rats with
      decompensated CHF, cortical vasoconstriction was severely blunted, whereas ET-1
      induced medullary vasodilation was significantly prolonged. This prolonged
      response was mimicked by IRL-1620, a specific ETB agonist, and partially
      abolished by NO synthase (NOS) blockade. In line with these findings, expression
      of ET-1, ETA and ETB receptors, and endothelial NOS (eNOS), assessed by RT-PCR,
      and eNOS immunoreactivity, assessed by Western blotting, was significantly higher
      in the medulla than in the cortex. Moreover, expression of ET-1 mRNA in the
      cortex and eNOS mRNA in the cortex and the medulla increased in proportion to the
      severity of heart failure. These findings indicate that CHF is associated with
      altered regulation of intrarenal blood flow, which reflects alterations in
      expression and activity of the ET and NO systems. It is further suggested that
      exaggerated NO activity in the medulla contributes to preservation of medullary
      blood flow in the face of cortical vasoconstriction in CHF.

PMID- 9575903
TI  - Isolation and characterization of the lower portion of the thin limb of Henle in
      primary culture.
AB  - To further characterize cells of the lower portion of the thin limb of Henle
      (TLH1p) under defined conditions in vitro, we developed a technique to enrich
      this cell population in suspension. TLH1p cells were isolated by enzymatic
      digestion of rat inner medulla, elimination of collecting ducts by lectin-coated
      beads, and differential centrifugation. Immunohistochemical staining of primary
      cultures of TLH1p cells with various markers revealed the preparations to be >
      90% pure. The hormonal stimulation pattern of PGE2 and cAMP production by
      arginine vasopressin, angiotensin II, and dopamine in the isolated cells also
      argued against significant contamination by other cell types. Staining with an
      antibody against the aquaporin-1 water channel showed the distribution of cells
      from the ascending and descending limbs to be approximately equal in the isolated
      population. This technique allows the enrichment of cells from the lower portion
      of the thin limb of Henle in suspension to a very high degree of purity with the
      option to start primary cultures. Because these segments of the tubular system in
      particular are relatively inaccessible for microdissection, the presented method
      renders the possibility of addressing new questions regarding these tubular
      segments under defined conditions in vitro.

PMID- 9575904
TI  - Copper metabolism in the kidney of rats administered copper and copper
      metallothionein.
AB  - To gain a greater understanding of the mechanism of Cu metabolism in kidneys of
      rats, using autofluorescence of Cu-metallothioneins (Cu-MTs) we revealed the
      behavior of Cu-MT in the kidneys of rats administered Cu-MT. Yellow and orange
      fluorescent signals of Cu-MT were observed in the cortex. By microscopic studies,
      Cu-MT was dominant in the proximal convolute tubular cells of the cortex. A high
      concentration of Cu-MT presented in the lysosome-like organelles of the proximal
      convolute tubular adjacent to the glomeruli. During the time course after the
      injection, the orange signal in lysosome-like organelles gradually converted to a
      yellow signal, indicating that the Cu-MT was involved in a degradation process in
      lysosomes by oxidation, and the MT mRNA increased in the cortex, although the
      immunoreactivity of MT was almost constant in the same region. These results
      suggested that Cu bound to the injected MT was released in lysosomes and became a
      new inducer of MT biosynthesis in the cortex. In conclusion, the biosynthesis and
      degradation of Cu-MT occur repeatedly in the proximal convolute tubular cells.

PMID- 9575905
TI  - Role of NO in cyclosporin nephrotoxicity: effects of chronic NO inhibition and NO
      synthases gene expression.
AB  - The role of nitric oxide (NO) during cyclosporin renal vasoconstriction was
      evaluated by glomerular hemodynamic and histological changes produced by chronic
      NO synthesis inhibition and neuronal (nNOS), inducible (iNOS), and endothelial
      (eNOS) NO syntheses mRNA expression in renal cortex and medulla.
      Uninephrectomized rats treated during 7 days with vehicle (Veh), cyclosporin A
      (CsA) 30 mg/kg, CsA + nitro-L-arginine methyl ester (L-NAME), and Veh + L-NAME
      (10 mg/dl) in the drinking water were studied. Increase in arterial pressure and
      afferent and efferent resistances, as well as decrease in glomerular plasma flow,
      ultrafiltration coefficient, and single-nephron glomerular filtration rate were
      significantly greater with CsA + L-NAME than with CsA alone. The increase in
      afferent resistance was higher with CsA + L-NAME than with Veh + L-NAME. In
      addition, glomerular thrombosis, proximal tubular vacuolization, and arteriolar
      thickening were more prominent. In renal cortex, eNOS mRNA expression exhibited a
      2.7-fold increase in CsA, whereas, in medulla, nNOS and iNOs expression were
      lower in CsA than in Veh, while eNOS tended to increase. Our results support the
      hypothesis that NO synthesis is enhanced at cortical level during CsA
      nephrotoxicity, counterbalancing predominantly preglomerular vasoconstriction.
      Higher NO production could be the result of increased eNOS mRNA expression.

PMID- 9575906
TI  - Localization of P2X1 purinoceptors by autoradiography and immunohistochemistry in
      rat kidneys.
AB  - P2 receptors have been identified in rat kidney by autoradiography, using the
      radioligand [3H] alpha, beta-methylene ATP, and by immunohistochemistry, using a
      polyclonal antibody to the P2X1 purinoceptor. They have been localized to the
      vascular smooth muscle of intrarenal arteries, including arcuate and interlobular
      arteries, and afferent arterioles, but not glomeruli, postglomerular efferent
      arterioles, or renal tubules. We conclude that at least some of the P2 receptors
      present on vascular smooth muscle are of the P2X1 subtype. The functional
      significance of these findings in the vascular control of the kidney is
      discussed.

PMID- 9575907
TI  - Tyrosine phosphorylation and association of p130Cas and c-Crk II by ANG II in
      vascular smooth muscle cells.
AB  - In cultured vascular smooth muscle cells (VSMC), angiotensin II (ANG II)
      stimulated tyrosine phosphorylation of multiple proteins including a 130-kDa
      protein. This 130-kDa protein was identified as a Crk-associated substrate,
      p130Cas. ANG II-stimulated tyrosine phosphorylation of p130Cas was rapid,
      concentration dependent, and inhibited by the AT1-receptor antagonist CV-11974.
      Neither downregulation of protein kinase C by long exposure of cells to phorbol
      12,13-dibutyrate nor blockade of Ca2+ mobilization by 1,2-bis(2-aminophenoxy)
      ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester had an effect on ANG II
      stimulated tyrosine phosphorylation of p130Cas. Stimulation with ANG II enhanced
      the specific association of p130Cas with c-Crk II. The time course of the
      association of p130Cas and c-Crk II was similar to that of tyrosine
      phosphorylation of p130Cas. c-Crk II was also tyrosine phosphorylated in response
      to ANG II. These results indicate that ANG II induces tyrosine phosphorylation of
      p130Cas and c-Crk II and their specific association, suggesting a potential role
      of the p130Cas-c-Crk II complex in ANG II signal transduction in VSMC.

PMID- 9575908
TI  - Hemodynamic effects of L-glutamate in NTS of conscious rats: a possible role of
      vascular nitrosyl factors.
AB  - This study examined peripheral mechanisms responsible for changes in mean
      arterial blood pressure, heart rate, and renal, mesenteric, and hindquarter
      vascular resistances produced by microinjections of L-glutamate (L-Glu) into the
      nucleus tractus solitarii (NTS) of conscious rats. Microinjection of L-Glu
      produced an initial pressor response, bradycardia, and vasoconstriction in each
      vascular bed. Subsequent hindquarter vasodilation was observed. After prazosin
      was administered, L-Glu produced initial hypotension that was probably due to
      reduced cardiac output. This hypotension was followed by hindquarter
      vasodilation. Inhibition of nitric oxide synthesis did not affect the initial
      hypotension or bradycardia in rats treated with prazosin, but the first
      microinjection of L-Glu after administration of prazosin and NG-nitro-L-arginine
      methyl ester (L-NAME) produced significantly greater hindquarter vasodilation
      than after administration of prazosin alone. Second and third microinjections of
      L-Glu produced significantly smaller hindquarter vasodilation. We conclude that
      1) hemodynamic effects produced by microinjection of L-Glu into the NTS of
      conscious rats involves activation of the sympathetic nervous system and 2)
      release of preformed nitrosyl factors may mediate vasodilation in the hindquarter
      vascular bed.

PMID- 9575909
TI  - Monkey corpus cavernosum relaxation mediated by NO and other relaxing factor
      derived from nerves.
AB  - Isolated monkey corpus cavernosum muscle strips contracted with prostaglandin F2
      alpha and treated with prazosin responded to transmural electrical stimulation
      with frequency-related relaxations that were abolished by tetrodotoxin. The
      nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) significantly
      attenuated but did not abolish the response; L-arginine reversed the inhibition.
      The neurogenic relaxation was not influenced in the strips treated with atropine
      or calcitonin gene-related peptide (CGRP)-(8-37), a CGRP-receptor antagonist, and
      those desensitized to vasoactive intestinal polypeptide (VIP) or pituitary
      adenylate cyclase-activating polypeptide (PACAP). Nerve fibers containing NADPH
      diaphorase were histochemically demonstrated in cavernous tissues. The relaxant
      response resistant to the NO synthase inhibitor was abolished by high K+ and
      tetrabutylammonium but was unaffected by glibenclamide, charybdotoxin, apamin,
      ouabain, SKF-525a, a cytochrome P-450 inhibitor, and oxyhemoglobin. It is
      concluded that neurogenic relaxations of monkey corpus cavernosum muscle is
      associated partly with NO released as a neurotransmitter and that other relaxing
      factor(s) possibly responsible for K+ channel opening also participates; however,
      the type of K+ channel involved is not determined. Acetylcholine, VIP, CGRP,
      PACAP, and the Na+ pump do not seem to be involved in the neurogenic relaxation.

PMID- 9575910
TI  - Metabolic inhibition in the perfused rat heart: evidence for glycolytic
      requirement for normal sodium homeostasis.
AB  - Subcellular compartmentalization of energy stores to support different myocardial
      processes has been exemplified by the glycolytic control of the ATP-sensitive K+
      channel. Recent data suggest that the control of intracellular sodium (Nai) may
      also rely on glycolytically derived ATP; however, the degree of this dependence
      is unclear. To examine this question, isolated, perfused rat hearts were exposed
      to hypoxia, to selectively inhibit oxidative metabolism, or iodoacetate (IAA, 100
      mumol/l), to selectively inhibit glycolysis. Nai and myocardial high-energy
      phosphate levels were monitored using triple-quantum-filtered (TQF) 23Na and 31P
      magnetic resonance spectroscopy, respectively. The effects of ion exchange
      mechanisms (Na+/Ca2+, Na+/H+) on Nai were examined by pharmacological
      manipulation of these channels. Nai, as monitored by shift reagent-aided TQF 23Na
      spectral amplitudes, increased by approximately 220% relative to baseline after
      45 min of perfusion with IAA, with or without rapid pacing. During hypoxia, Nai
      increased by approximately 200% during rapid pacing but did not increase in
      unpaced hearts or when the Na+/H+ exchange blocker ethylisopropylamiloride (EIPA,
      10 mumol/l) was used. Neither EIPA nor a low-Ca2+ perfusate (50 mumol/l) could
      prevent the rise in Nai during perfusion with IAA. Myocardial function and high
      energy phosphate stores were preserved during inhibition of glycolysis with IAA
      and continued oxidative metabolism. These results suggest that glycolysis is
      required for normal Na+ homeostasis in the perfused rat heart, possibly because
      of preferential fueling of Na-K-adenosinetriphosphatase by glycolytically derived
      ATP.

PMID- 9575912
TI  - Entropy measures of heart rate variation in conscious dogs.
AB  - Our goal was to determine the contributions of sympathetic and parasympathetic
      activity to entropy measures of heart rate variability (HRV). We compared our
      results with two commonly used methods to analyze HRV: standard deviation (SDNN)
      and power spectral analysis (HF norm). Beat-by-beat analysis of R-R intervals was
      performed in conscious dogs. The R-R intervals were analyzed with approximate
      entropy (ApEn) and entropy of symbolic dynamics (SymDyn) to assess the effects of
      reducing system complexity. This was achieved by pharmacologically inhibiting
      sympathetic, parasympathetic, and total autonomic nervous system regulation of
      heart rate. Three conditions were examined: rest, standing, and systemic
      hypotension. At rest or standing, sympathetic inhibition (propranolol) had no
      effect on ApEn or SymDyn, whereas parasympathetic (atropine) and combined
      (propranolol + atropine) inhibition reduced both entropy measures to near zero.
      Systemic hypotension reduced both entropy measures in intact dogs. When
      hypotension was induced after sympathetic inhibition, ApEn was increased compared
      with hypotension alone, whereas parasympathetic inhibition with hypotension
      resulted in near-zero ApEn. Changes in the entropy measures of HRV were
      directionally similar to changes in SDNN and HF norm. These results indicate that
      the entropy of R-R intervals reflects parasympathetic modulation of heart rate.

PMID- 9575911
TI  - Does postsynaptic alpha 1-adrenergic receptor supersensitivity contribute to
      autonomic dysreflexia?
AB  - Quadriplegics often experience periods of severe hypertension known as autonomic
      dysreflexia. Clinically, these events have been well documented, but the
      mechanisms for mediating autonomic dysreflexia remain unclear. We used a chronic
      rat model to investigate the potential development of supersensitivity at
      postsynaptic alpha 1-adrenergic receptors as a contributing factor to the
      exaggerated sympathetic response characteristic of autonomic dysreflexia. Adult
      male Wistar and Sprague-Dawley rats were anesthetized and given spinal
      transection at T5. After 30 days, rats were reanesthetized and arterial and
      venous catheters implanted. Twenty-four hours later, colorectal distension (CRD)
      was used to evoke autonomic dysreflexia in conscious, spinalized rats. To gauge
      changes in alpha 1-receptor sensitivity, we assessed mean arterial pressure (MAP)
      in response to intravenous phenylephrine (PE) infusions. No consistent
      differences were observed between intact and spinalized rats. Therefore,
      supersensitivity of alpha 1-receptors cannot completely account for the
      hypertensive bouts associated with autonomic dysreflexia. In addition, while
      attempting to develop an appropriate model for autonomic dysreflexia, we
      discovered that spinalized Wistar rats exhibited MAP responses characteristic of
      autonomic dysreflexia, whereas lesioned Sprague-Dawley rats did not, when
      subjected to CRD. Thus Wistar rats provide a better animal model for autonomic
      dysreflexia.

PMID- 9575913
TI  - KATP channels are common mediators of ischemic and calcium preconditioning in
      rabbits.
AB  - Calcium preconditioning (CPC), like ischemic preconditioning (IPC), reduces
      myocardial infarct size in dogs and rats. ATP-sensitive potassium (KATP) channels
      induce cardioprotection of IPC in these animals. To determine whether KATP
      channels mediate both IPC and CPC, pentobarbital sodium-anesthetized rabbits
      received 30 min of coronary artery occlusion followed by 180 min of reperfusion.
      IPC was elicited by 5 min of occlusion and 10 min of reperfusion, and CPC was
      elicited by two cycles of 5 min of calcium infusion with an interval period of 15
      min. Infarct size expressed as a percentage of the area at risk was 38 +/- 3%
      (mean +/- SE) in controls. IPC, CPC, and pretreatment with a KATP channel opener,
      cromakalim, all reduced infarct size to 13 +/- 2, 17 +/- 2, and 12 +/- 3%,
      respectively (P < 0.01 vs. controls). Glibenclamide, a KATP channel blocker
      administered 45 min (but not 20 min) before sustained ischemia, attenuated the
      effects of IPC and CPC (31 +/- 4 and 41 +/- 6%, respectively). Thus KATP channel
      activation appears to contribute to these two types of cardioprotection in
      rabbits.

PMID- 9575914
TI  - High-dose lidocaine does not affect defibrillation efficacy: implications for
      defibrillation mechanisms.
AB  - This study assessed the effect of low (10 mg.kg-1.h-1) and very high (18 mg.kg
      1.h-1) doses of lidocaine on defibrillation energy requirements (DER) to relate
      changes in indexes of sodium-channel blockade with changes in DER values using a
      dose-response study design. In group 1 (control; n = 6 pigs), DER values were
      determined at baseline and during treatment with 5% dextrose in water (D5W) and
      with D5W added to D5W. In group 2 (n = 7), DER values were determined at baseline
      and during treatment with low-dose lidocaine followed by high-dose lidocaine. In
      group 3 (n = 3), DER values were determined at baseline and high-dose lidocaine.
      Group 3 controlled for the order of lidocaine treatment with the addition of high
      dose lidocaine after baseline. DER values in group 1 did not change during D5W.
      In group 2, low-dose lidocaine increased DER values by 51% (P = 0.01), whereas
      high-dose lidocaine added to low-dose lidocaine reduced DER values back to within
      6% of baseline values (P = 0.02, low dose vs. high dose). DER values during high
      dose lidocaine in group 3 also remained near baseline values (16.2 +/- 2.7 to
      12.9 +/- 2.7 J), demonstrating that treatment order had no impact on group 2.
      Progressive sodium-channel blockade was evident as incremental reduction in
      ventricular conduction velocity as the lidocaine dose increased. Lidocaine also
      significantly increased ventricular fibrillation cycle length as the lidocaine
      dose increased. However, the greatest increase in DER occurred when ventricular
      fibrillation cycle length was minimally affected, demonstrating a negative
      correlation (P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose
      response curve. At very high lidocaine doses, DER values are similar to baseline
      and tend to decrease rather than increase. Increased refractoriness during
      ventricular fibrillation may be the electrophysiological mechanism by which high
      dose lidocaine limits the adverse effects that low-dose lidocaine has on DER
      values. However, there is a possibility that an unidentified action of lidocaine
      is responsible for these effects.

PMID- 9575916
TI  - Molecular characterization of rabbit CPP32 and its function in vascular smooth
      muscle cell apoptosis.
AB  - Vascular remodeling in atherogenesis is marked not only by cellular proliferation
      and migration but is also impacted by apoptotic cell death. Extensive studies
      have focused on the signal transduction events leading to apoptosis. CPP32, a
      member of the caspase/interleukin-1 beta-converting enzyme (ICE) protease family,
      has emerged as a central player in several reports of apoptosis pathways.
      Vascular smooth muscle cells (SMC) undergo apoptosis after treatment with various
      stimuli, including nitric oxide (NO) donors, such as sodium nitroprusside (SNP,
      0.1-1 mM). The aim of the present study was to evaluate the role of CPP32 in SNP
      induced apoptosis of SMC. We isolated a rabbit CPP32 cDNA by using degenerate
      primers and polymerase chain reaction technique. The predicted protein encoded by
      this cDNA contains the conserved sequence (QACRG) necessary for covalent linkage
      to poly(ADP-ribose) polymerase (PARP) as well as the three amino acids
      responsible for substrate recognition and catalysis reported in other caspase
      members. Using a segment of this cDNA as a probe, we found no change of CPP32
      mRNA in cultured arterial SMC before and after SNP treatment. We also measured
      the protease activity of CPP32 against a chromophore p-nitroaniline (pNA)-labeled
      substrate, DEVD-pNA. Our results showed a dose-dependent increase of CPP32
      activity in SMC, with a maximal 10-fold increase after SNP treatment. Addition of
      a competitive CPP32 inhibitor, DEVD-CHO, produced a 50% reduction in maximal
      stimulation. Immunoblot analysis illustrated that SNP treatment induced
      proteolytic cleavage of CPP32 into its enzymatically active subunit p17 as well
      as the degradation of PARP into a 85-kDa fragment. We further demonstrated that
      incubation of cultured SMC with DEVD-CHO significantly reduced SNP-induced DNA
      fragmentation. DNA fragmentation analysis was carried out using several methods
      including a cell death detection enzyme-linked immunosorbent assay kit, in situ
      end labeling, and DNA electrophoresis in agarose gel. Our data indicate that
      CPP32 mRNA is constitutively expressed in rabbit SMC and activation of CPP32
      protein has a pivotal role in SNP-induced SMC apoptosis.

PMID- 9575915
TI  - Reduction in arterial compliance alters carotid baroreflex control of cardiac
      output in a model of hypertension.
AB  - Baroreflex regulation of cardiac output is determined by the performance of the
      heart as well as the available blood flow returning to the heart (i.e., venous
      return). We hypothesized that a decrease in arterial compliance (C(a)) would
      affect carotid baroreflex control of cardiac output by altering the slope of the
      venous return curve (VR curve). Baroreflex control of systemic arterial pressure
      (Pa), central venous pressure (Pv), heart rate, cardiac output (CO), and
      peripheral vascular resistance (R) were determined during bilateral carotid
      occlusion (BCO) in spontaneously hypertensive (hypertensive, HT) and Sprague
      Dawley (normotensive, NT) rats. C(a) was determined from the rate of arterial
      pressure decay when CO was transiently stopped, and the VR curve was obtained
      during graded inflation of a vascular balloon positioned in the right atrium. The
      inverse slope of the VR curve was used as an index of the resistance to venous
      return (RVR). The baseline slope of the VR curve was -50.5 +/- 3.3 vs. -35.5 +/-
      2.6 ml.kg-1.min-1.mmHg-1 in NT vs. HT, respectively (P < 0.05). Control values of
      Pa (96 +/- 5 vs. 124 +/- 8 mmHg) and R [0.43 +/- 0.04 vs. 0.80 +/- 0.07
      peripheral resistance units (PRU)] were reduced in NT, whereas Ca (0.062 +/- 0010
      vs. 0.036 +/- 0.003 ml.kg-1.mmHg-1) was elevated in NT vs. HT, respectively (P <
      0.05). Analysis of the pressure dependence of C(a) demonstrated that C(a) was a
      nonlinear function of Pa, and the exponential decay constant for the C(a)-Pa
      relationship was reduced in HT (0.0055 +/- 0.0012 vs. 0.0012 +/- 0.0002 min, NT
      vs. HT, P < 0.05). Baroreflex activation by BCO significantly increased Pa (delta
      Pa, 20 +/- 4 vs. 28 +/- 3 mmHg) and R (delta R, 0.16 +/- 0.04 vs. 0.24 +/- 0.06
      PRU) in NT vs. HT, respectively. However, BCO significantly decreased CO in NT
      but not HT (delta CO, -24 +/- 5 vs. -4 +/- 6 ml.kg-1.min-1, P < 0.05). In NT, RVR
      was increased 39 +/- 9% during BCO (P < 0.05), whereas RVR increased 8 +/- 3% in
      HT (P = NS). From these findings, we conclude that the difference in baroreflex
      control of CO is mediated, in part, by the reduction in C(a), which minimized the
      baroreflex-evoked increase in RVR.

PMID- 9575917
TI  - Myocardial contractile depression from high-frequency vibration is not due to
      increased cross-bridge breakage.
AB  - Experiments were conducted in 10 isolated rabbit hearts at 25 degrees C to test
      the hypothesis that vibration-induced depression of myocardial contractile
      function was the result of increased cross-bridge breakage. Small-amplitude
      sinusoidal changes in left ventricular volume were administered at frequencies of
      25, 50, and 76.9 Hz. The resulting pressure response consisted of a depressive
      response [delta Pd(t), a sustained decrease in pressure that was not at the
      perturbation frequency] and an infrequency response [delta Pf(t), that part at
      the perturbation frequency]. delta Pd(t) represented the effects of contractile
      depression. A cross-bridge model was applied to delta Pf(t) to estimate cross
      bridge cycling parameters. Responses were obtained during Ca2+ activation and
      during Sr2+ activation when the time course of pressure development was slowed by
      a factor of 3. delta Pd(t) was strongly affected by whether the responses were
      activated by Ca2+ or by Sr2+. In the Sr(2+)-activated state, delta Pd(t) declined
      while pressure was rising and relaxation rate decreased. During Ca2+ and Sr2+
      activation, velocity of myofilament sliding was insignificant as a predictor of
      delta Pd(t) or, when it was significant, participated by reducing delta Pd(t)
      rather than contributing to its magnitude. Furthermore, there was no difference
      in cross-bridge cycling rate constants when the Ca(2+)-activated state was
      compared with the Sr(2+)-activated state. An increase in cross-bridge detachment
      rate constant with volume-induced change in cross-bridge distortion could not be
      detected. Finally, processes responsible for delta Pd(t) occurred at slower
      frequencies than those of cross-bridge detachment. Collectively, these results
      argue against a cross-bridge detachment basis for vibration-induced myocardial
      depression.

PMID- 9575918
TI  - Opposing effects of alpha 1-adrenergic receptor subtypes on Ca2+ and pH
      homeostasis in rat cardiac myocytes.
AB  - We examined the effect of alpha 1-adrenergic receptor (AR) subtypes on
      contraction, cytosolic Ca2+ concentration ([Ca2+]i), and cytosolic pH (pHi) of
      rat ventricular myocytes loaded with the Ca2+ indicator indo 1 or the pH
      indicator carboxyseminaphthorhodafluor-1. Nonselective alpha 1-AR stimulation was
      effected with phenylephrine plus nadolol. alpha 1-AR subtype stimulation was
      achieved with alpha 1-AR and chloroethylclonidine (CEC) or with alpha 1-AR and WB
      4101. Cells were in bicarbonate buffer with 0.5 mM Ca2+ and were electrically
      stimulated at 0.5 Hz. Results show that 1) nonselective alpha 1-AR stimulation
      increased twitch and [Ca2+]i transient amplitudes, myofilament response to Ca2+,
      and pHi; 2) alpha 1-AR plus CEC increased twitch and [Ca2+]i transient amplitudes
      and also enhanced myofilament response to Ca2+ via cytosolic alkalinization; 3)
      alpha 1-AR plus WB-4101 decreased twitch and [Ca2+]i transient amplitudes and
      also pHi; and 4) cytosolic acidification due to alpha 1-AR plus WB-4101 was
      abolished by protein kinase C inhibition (staurosporine pretreatment) or
      downregulation (prolonged exposure to phorbol esters). In summary, the net
      effects of alpha 1-adrenergic stimulation on contraction, [Ca2+]i, and pHi are
      due to opposing WB-4101- and CEC-sensitive alpha 1-AR subtype signaling pathways.

PMID- 9575919
TI  - Conduction between isolated rabbit Purkinje and ventricular myocytes coupled by a
      variable resistance.
AB  - Conduction at the Purkinje-ventricular junction (PVJ) demonstrates unidirectional
      block under both physiological and pathophysiological conditions. Although this
      block is typically attributed to multidimensional electrotonic interactions, we
      examined possible membrane-level contributions using single, isolated rabbit
      Purkinje (P) and ventricular (V) myocytes coupled by an electronic circuit. When
      we varied the junctional resistance (Rj) between paired V myocytes, conduction
      block occurred at lower Rj values during conduction from the smaller to larger
      myocyte (115 +/- 59 M omega) than from the larger to smaller myocyte (201 +/- 51
      M omega). In Purkinje-ventricular myocyte pairs, however, block occurred at lower
      Rj values during P-to-V conduction (85 +/- 39 M omega) than during V-to-P
      conduction (912 +/- 175 M omega), although there was little difference in the
      mean cell size. Companion computer simulations, performed to examine how the
      early platea currents affected conduction, showed that P-to-V block occurred at
      lower Rj values when the transient outward current was increased or the calcium
      current was decreased in the model P cell. These results suggest that intrinsic
      differences in phase 1 repolarization can contribute to unidirectional block at
      the PVJ.

PMID- 9575921
TI  - Alterations in dynamic heart rate control in the beta 1-adrenergic receptor
      knockout mouse.
AB  - beta 1-Adrenergic receptors (beta 1-ARs) are key targets of sympathetic nervous
      system activity and play a major role in the beat-to-beat regulation of cardiac
      chronotropy and inotropy. We employed a beta 1-AR gene knockout model to test the
      hypothesis that beta 1-AR function is critical for maintenance of resting heart
      rate and baroreflex responsiveness and, on the basis of its important role in
      regulating chronotropy and inotropy, is also required for maximal exercise
      capacity. Using an awake unrestrained mouse model, we demonstrate that resting
      heart rate and blood pressure are normal in beta 1-AR knockouts and that the
      qualitative responses to baroreflex stimulation are intact. Chronotropic reserve
      in beta 1-AR knockouts is markedly limited, with peak heart rates approximately
      200 beats/min less than wild types. During graded treadmill exercise, heart rate
      is significantly depressed in beta 1-AR knockouts at all work loads, but despite
      this limitation, there are no reductions in maximal exercise capacity or
      metabolic indexes. Thus, in mice, the beta 1-AR is not essential for either
      maintenance of resting heart rate or for maximally stressed cardiovascular
      performance.

PMID- 9575920
TI  - Continuous release of vasodilator prostanoids contributes to regulation of
      resting forearm blood flow in humans.
AB  - Continuous release of nitric oxide contributes to the maintenance of resting tone
      in the human forearm and coronary circulations; however, evidence for a similar
      role of vasodilator prostanoids such as prostacyclin is lacking. We examined
      whether continuous release of prostacyclin contributes to basal forearm blood
      flow. Flow was measured using venous occlusion plethysmography in 38 healthy
      volunteers [mean age 21.3 +/- 2.5 yr (+/- SD); 13 female, 25 male] at rest, after
      administration of three incremental intra-arterial infusions of either the
      cyclooxygenase inhibitor aspirin or placebo, and before and after administration
      of the endothelium-dependent and -independent dilators acetylcholine (30
      micrograms/min) and nitroprusside (1 microgram/min). To assess the effect of
      aspirin on the production of prostacyclin, plasma 6-keto prostaglandin F1 alpha
      (6-keto-PGF1 alpha; the stable metabolite of prostacyclin) was measured by
      simultaneous arterial and venous sampling. Aspirin produced a time- and dose
      dependent reduction in forearm blood flow, resulting in a 32% decrease at the
      highest dose. The effect was maximal after 10 min. Flow at rest and after aspirin
      doses of 1, 3, and 10 mg/min was 2.6 +/- 0.2, 2.3 +/- 0.2, 2.1 +/- 0.2, and 1.8
      +/- 0.2 ml.100 ml forearm tissue-1.min-1, respectively (means +/- SE, P < 0.001).
      Commensurate with these data, the net forearm production of 6-keto-PGF1 alpha was
      52.9 +/- 16.4, 11.7 +/- 8.6, 18.7 +/- 8.5, and 12.0 +/- 12.5 pg.100 ml forearm
      tissue-1.min-1 for the respective doses (P = 0.04). No time-dependent reduction
      in flow was seen in subjects with vehicle infusion. Aspirin did not affect the
      responses to acetylcholine or nitroprusside. These data suggest that continuous
      release of prostacyclin plays a role in the maintenance of resting forearm blood
      flow. There appears to be a direct link between the reduction in flow with
      aspirin and inhibition of prostacyclin production.

PMID- 9575922
TI  - Low-frequency arterial pressure fluctuations do not reflect sympathetic outflow:
      gender and age differences.
AB  - Low-frequency arterial pressure oscillations (Mayer waves) have been proposed as
      an index of vascular sympathetic outflow. However, cross-sectional differences in
      these pressure oscillations may not reflect different levels of sympathetic
      nervous outflow in humans. Three groups of healthy subjects with
      characteristically different sympathetic nervous outflow were studied: young
      females (n = 10, 18-28 yr), young males (n = 11, 18-29 yr), and older males (n =
      13, 60-72 yr). Average R-R interval, arterial pressures, and systolic pressure
      variability at the Mayer wave frequency (0.05-0.15 Hz) did not differ among the
      three groups. Diastolic pressure Mayer wave variability was similar in young
      females vs. young males (39 +/- 10 vs. 34 +/- 5 mmHg2) and lower in older males
      vs. young males (14 +/- 2 mmHg2; P < 0.05). In contrast, muscle sympathetic
      activity was lowest in young females (892 +/- 249 total activity/min) and highest
      in older males (3,616 +/- 528 total activity/min; both P < 0.05 vs. young males:
      2,505 +/- 285 total activity/min). Across the three groups, arterial pressure
      Mayer wave variability did not correlate with any index of sympathetic activity.
      Our results demonstrate that arterial pressure Mayer wave amplitude is not a
      surrogate measure of vascular sympathetic outflow.

PMID- 9575923
TI  - A multiunit model of solute and water removal by inner medullary vasa recta.
AB  - A recent model of volume and solute microcirculatory exchange in the renal
      medulla based on a single descending vasa rectum (DVR) was extended to account
      for the varying number of vessels along the corticomedullary axis. The assumption
      that concentration polarization at the walls of ascending vasa recta (AVR) during
      volume uptake eliminates transmural oncotic pressure gradients was examined. In
      this limiting case, small hydrostatic pressure gradients can drive AVR volume
      uptake if the pressure in the interstitium exceeds that in the AVR lumen. The
      calculated hydraulic pressure difference across AVR yielding agreement between
      predicted and measured values of AVR-to-DVR blood flow rate ratios was found to
      be smaller than the reported maximum pressure difference AVR can sustain.
      Simulations also confirmed previous conclusions suggesting that the presence of
      urea transporters in DVR counterbalances that of water channels that would
      otherwise decrease the efficiency of small solute trapping in the renal medulla.

PMID- 9575924
TI  - Spectral analysis of heart rate, arterial pressure, and muscle sympathetic nerve
      activity in normal humans.
AB  - We investigated the frequency components of fluctuations in heart rate, arterial
      pressure, respiration, and muscle sympathetic nerve activity (MSNA) in 11 healthy
      women using an autoregressive model and examined the relation among variables
      using Akaike's relative power contribution analysis with multivariate
      autoregressive model fitting. Power spectral analysis of MSNA revealed two peaks,
      with low-frequency (LF) and high-frequency (HF) components. The LF component of
      MSNA was a major determinant of the LF component of arterial pressure and R-R
      interval variability (0.70 +/- 0.07 and 0.18 +/- 0.05, respectively). The effect
      of the LF component of MSNA on arterial pressure showed no change in response to
      propranolol but was diminished (0.35 +/- 0.08) by phentolamine (P < 0.02). The
      effect of the LF component of MSNA on R-R interval was not altered by
      pharmacological sympathetic nerve blockade. The HF component of MSNA did not
      influence other variables but was influenced by R-R interval, arterial pressure,
      and respiration. These findings indicate that the LF component of MSNA reflects
      autonomic oscillations, whereas the HF component is passive and influenced by
      other cardiovascular variables.

PMID- 9575925
TI  - Novel catheterization technique for the in vivo measurement of pulmonary vascular
      responses in rats.
AB  - A novel cardiac catheterization technique was devised to investigate the
      pulmonary arterial pressure-blood flow relationship in intact spontaneously
      breathing rats (ISBR) under physiological conditions with constant left atrial
      pressure and controlled blood flow within the normal range. Observations using
      this new technique in vivo were contrasted with data derived with isolated
      perfused rat lungs in vitro. Unlike results in in vitro isolated perfused rat
      lungs, the pressure-flow curves in vivo were curvilinear, with pulmonary artery
      pressure increasing more rapidly at low pulmonary blood flows of 4-8 ml/min and
      less rapidly at higher flow rates. Pressure-flow curves were reproducible and
      were not altered by 1-1.5 h of arrested perfusion, cyclooxygenase blockade, or
      perfusion with aortic or mixed venous blood. In contrast to results in in vitro
      isolated perfused rat lungs, NG-nitro-L-arginine methyl ester (L-NAME) increased
      pulmonary arterial pressure at all but the lowest flow rates with a slight effect
      on the curvilinear pressure-flow relationship. L-NAME reversed pulmonary
      vasodilator responses to acetylcholine and bradykinin and enhanced the pulmonary
      vasodilator response to nitroglycerin. The present data suggest that actively
      induced pulmonary hypertension is under greater control by endothelium-derived
      relaxing factor (EDRF). Unlike previous results in in vitro perfused rat lungs,
      results in ISBR demonstrate that the pulmonary vasodilator response to
      adrenomedullin-(13-52) is not mediated by calcitonin gene-related peptide
      receptors, which are not coupled to the release of EDRF. These results indicate
      that this novel technique may provide a useful model for the study of the
      pulmonary circulation in the intact chest rat.

PMID- 9575927
TI  - Energy provision from glycogen, glucose, and fatty acids on adrenergic
      stimulation of isolated working rat hearts.
AB  - We postulated that glycogen is a significant energy substrate compared with fatty
      acids and glucose in response to adrenergic stimulation of working rat hearts.
      Oxidation rates were determined at 1-min intervals by release of 3H2O from [9,10
      (3)H]oleate (0.4 mM, 1% albumin) and 14CO2 from exogenous [U-14C]glucose (5 mM)
      or, by a pulse-chase method, from [14C]glycogen. We estimated the 14C enrichment
      of glycogen metabolized at each time point to determine true rates of glycogen
      use. Based on the pattern of glycogen enrichment over time, glycogenolysis did
      not exhibit a high degree of preference for newly synthesized glycogen.
      Epinephrine (1 microM) increased contractile performance 86% but did not
      stimulate oleate oxidation. The increased energy demand was supplied by
      carbohydrates, initially by a burst of glycogenolysis (contributing 35% to total
      ATP synthesis for 5 min) and followed by delayed increase in the use of exogenous
      glucose (eventually contributing 29% to ATP synthesis). On the basis of the
      release of 14CO2 and [14C]lactate specifically from glucose or glycogen, we found
      that a larger portion of glycogen was oxidized compared with exogenous glucose,
      augmenting the yield of ATP from glycogen. Thus the heart responds to an acute
      increase in energy demand by selective oxidation of glycogen.

PMID- 9575926
TI  - Preconditioning and adenosine in I/R-induced leukocyte-endothelial cell
      interactions.
AB  - Recently, it was reported that preconditioning reduced leukocyte adhesion
      following ischemia-reperfusion (I/R). We further examined the effects of
      preconditioning and adenosine not only on neutrophil adhesion but also on
      neutrophil rolling and vascular dysfunction. Intravital microscopy revealed a
      decrease in neutrophil rolling velocity; a profound increase in neutrophil
      rolling, adhesion, and microvascular dysfunction; and a reduction in venular
      shear rates associated with 60 min ischemia and 60 min reperfusion in the feline
      mesentery. Preconditioning (5 min ischemia/10 min reperfusion) prevented
      subsequent I/R-induced slow neutrophil rolling, neutrophil adhesion, and
      microvascular dysfunction but did not affect the flux of rolling neutrophils.
      Adenosine deaminase A1 and A2 adenosine-receptor antagonists had only minor
      effects on the preconditioning responses. Pretreatment of vessels with exogenous
      adenosine reduced neutrophil adhesion and microvascular permeability and improved
      neutrophil rolling velocity and shear forces associated with I/R, but the flux of
      rolling neutrophils was not affected. Finally, in vitro experiments revealed that
      adenosine had absolutely no direct effect on neutrophil-endothelial cell
      interactions. In conclusion, our data suggest that adenosine plays only a minor
      role in preconditioned vessels and that adenosine per se may not directly affect
      neutrophil-endothelial cell interactions.

PMID- 9575928
TI  - Dissociation between volume blood flow and laser-Doppler signal from rat muscle
      during changes in vascular tone.
AB  - Although the laser-Doppler flowmetry (LDF) signal from skeletal muscle has been
      shown to provide a good measure of blood flow under some conditions, its behavior
      during administration of vasoactive substances has never been addressed. The aims
      of this study were to compare 1) changes in LDF signal with those in total muscle
      blood flow measured with radioactive microspheres after ganglionic blockade
      (chlorisondamine) and during administration of angiotensin II (ANG II),
      phenylephrine (PE), and isoproterenol (Iso) and 2) changes in vascular resistance
      estimated by the two techniques. The LDF signal from the biceps femoris muscle
      was investigated in anesthetized male Wistar rats. Ganglionic blockade led to a
      significant (P < 0.05) fall in mean arterial pressure (MAP) [medians (lower,
      upper quartiles): 78 (72, 83) vs. 127 (114, 138) mmHg under basal conditions],
      muscle blood flow (MBF, microsphere technique; 61%), and the LDF signal (29%).
      Muscle vascular resistance (MVR = MAP/MBF) was increased (64%, P < 0.05), but
      vascular resistance estimated as MAP/LDF signal (MVRLDF) was unchanged. During
      ANG II and PE infusions, MAP rose (P < 0.05) to 178 (155, 194) and 127 (124, 142)
      mmHg, respectively; MBF did not change compared with the preinfusion
      (postganglionic blockade) level and remained significantly (P < 0.05) lower than
      baseline, whereas the LDF signal increased up to a level not different from
      baseline. MVR rose and was significantly (P < 0.05) higher than baseline, whereas
      MVRLDF did not differ significantly from baseline. During Iso infusion, MAP fell
      [58 (56, 60) vs. 94 (92, 102) mmHg, P < 0.05], the LDF signal was reduced (49%, P
      < 0.05) despite a large increase in MBF (139%, P < 0.05), and MVR fell (74%, P <
      0.05), whereas MVRLDF did not change vs. preinfusion level. Our results suggest
      that 1) changes in the LDF signal from muscle may not correlate with changes in
      total muscle blood flow measured by the microsphere technique during infusion of
      vasoactive substances and 2) the use of LDF data for estimation of MVR during
      changes in vascular tone in rat skeletal muscle is probably not appropriate.

PMID- 9575929
TI  - Analysis of responses to adrenomedullin-(13-52) in the pulmonary vascular bed of
      rats.
AB  - The effects of human adrenomedullin-(13-52) [hADM-(13-52)] were investigated in
      the rat pulmonary vascular bed and in isolated rings from the rat pulmonary
      artery (PA). Under conditions of controlled blood flow and constant left atrial
      pressure when tone was increased with U-46619, injection of hADM-(13-52) produced
      dose-related decreases in lobar arterial pressure. Pulmonary vasodilator
      responses in the intact rat and vasorelaxant responses to hADM-(13-52) in rat PA
      rings were inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and L-N5-(1
      iminoethyl)-ornithine hydrochloride (L-NIO). Vasorelaxant responses to hADM-(13
      52) were also inhibited by methylene blue, endothelium removal, hADM-(26-52), and
      iberiotoxin, whereas meclofenamate, calcitonin gene-related peptide-(8-37) [CGRP
      (8-37)], glibenclamide, and apamin were without effect. Because vasorelaxant
      responses to NS-1619, a large-conductance Ca(2+)-activated K+ channel agonist,
      were not altered by L-NAME and vasorelaxant responses to acetylcholine and CGRP
      were not altered by hADM-(26-52), the present data suggest that ADM-(13-52) acts
      on a receptor in the pulmonary vascular bed that is coupled to endothelial nitric
      oxide release. These data suggest that this nitric oxide release may lead to
      guanosine 3',5'-cyclic monophosphate-dependent K+ channel activation, which
      produces a pulmonary vasorelaxant response through hyperpolarization of vascular
      smooth muscle cells. The present data suggest that ADM-(13-52) modulates receptor
      mediated, but not voltage-dependent, pulmonary vascular contraction by
      influencing Ca2+ influx. These results suggest that the ADM fragment, hADM-(13
      52), acts as an endothelium-dependent vasodilator agent in the pulmonary vascular
      bed of the rat.

PMID- 9575930
TI  - Local L-NAME decreases blood flow and increases leukocyte adhesion via CD18.
AB  - Local inhibition of nitric oxide (NO) synthesis with L-arginine analogs such as
      NG-nitro-L-arginine methyl ester (L-NAME) decreased red blood cell velocity
      (VRBC) in capillaries and increased leukocyte adhesion in postcapillary venules
      in rat skeletal muscle. The goal of the present study was to determine the
      mechanism of this response to L-NAME. Using intravital videomicroscopy, we
      examined blood flow in the surface microvasculature of rat extensor digitorum
      longus muscle. L-NAME (30 mM in the pipette) locally applied to capillaries (300
      microns from feeding arteriole) reduced VRBC [control VRBC = 244 +/- 53 (SE)
      microns/s; delta VRBC = -52 +/- 8%] and increased leukocyte adhesion (from 0.2 +/
      0.01 to 1.3 +/- 0.3 cells/100 microns) in control animals. Systemic pretreatment
      with fucoidan (selectin binder), superoxide dismutase and catalase (extracellular
      antioxidants), dimethylthiourea (intracellular antioxidant), or ketotifen (mast
      cell stabilizer) did not alter this response. Pretreatment with CL26, an anti
      CD18 antibody, abolished the L-NAME response. Our results suggest that L-NAME
      increased leukocyte-endothelial interactions via an effect on CD11/CD18 or its
      ligand, intercellular adhesion molecule.

PMID- 9575931
TI  - Brain "ouabain," ANG II, and sympathoexcitation by chronic central sodium loading
      in rats.
AB  - Both brain ouabain-like activity ("ouabain") and brain angiotensin II (ANG II)
      contribute to the sympathoexcitatory and pressor responses to high sodium intake
      in spontaneously hypertensive (SHR) and Dahl salt-sensitive (Dahl S) rats. To
      assess whether increases in cerebrospinal fluid (CSF) sodium can mimic this
      pattern of changes, Wistar rats were chronically infused with artificial CSF
      (aCSF) or sodium-rich aCSF (0.8 or 1.2 M sodium) intracerebroventricularly
      through osmotic minipumps for 14 days. Sodium-rich aCSF (0.8 M) was also infused
      intracerebroventricularly for 2 wk concomitantly with either antibody Fab
      fragments that bind ouabain and related steroids with high affinity, gamma
      globulins as control (200 micrograms/day for both), or the AT1 blocker losartan
      (1 mg.kg-1.day-1). Sodium-rich aCSF increased CSF sodium from 146 +/- 2 to 152 +/
      2 (0.8 M) and 160 +/- 3 (1.2 M) mmol/l, and increased brain "ouabain" in the
      hypothalamus, pituitary, and pons. In conscious rats, sodium-rich aCSF increased
      baseline mean arterial pressure (MAP), enhanced MAP, heart rate (HR), and renal
      sympathetic nerve activity (RSNA) responses to intracerebroventricular alpha 2
      adrenoceptor agonist guanabenz and air stress, and desensitized arterial and
      cardiopulmonary baroreflex control of HR and RSNA. These effects were largely
      prevented by intracerebroventricular Fab fragments or losartan. Thus, in Wistar
      rats, both brain "ouabain" and the brain renin-angiotensin system contribute to
      sympathoexcitation, impairment of baroreflexes, and hypertension caused by
      chronically increased CSF sodium. The similar patterns of changes caused by CSF
      sodium in Wistar rats and by high sodium intake in SHR and Dahl S rats indicate
      that if high sodium intake increases central sodium, such changes may contribute
      to sympathoexcitation and hypertension.

PMID- 9575932
TI  - Frequency response characteristics of sympathetically mediated vasomotor waves in
      humans.
AB  - In a recent study, we demonstrated that transmission from peripheral sympathetic
      nerves to vascular smooth muscles is strongest in the frequency band from 0.2 to
      0.5 Hz in conscious rats. In contrast, sympathetic modulation of vasomotor tone
      in humans is suggested to be reflected in the power spectrum of arterial blood
      pressure in a frequency range centered around approximately 0.1 Hz. Therefore, we
      addressed whether frequency response characteristics of sympathetic transmission
      from peripheral sympathetic nerves to vascular smooth muscles in humans differ
      from those in rats. In 12 male subjects, skin-sympathetic fibers of the left
      median nerve were electrically stimulated via microneurography needles with
      stimulation frequencies ranging from 0.01 to 0.5 Hz. Simultaneously, blood flow
      in the innervated skin area at the palm of the ipsilateral hand was recorded by a
      laser-Doppler device. The skin blood flow in the same area of the contralateral
      hand was recorded as a control. Median nerve stimulation produced transient
      decreases in skin blood flow in the ipsilateral hand. At frequencies ranging from
      0.025 to 0.10 Hz, median nerve stimulation evoked high-power peaks at the same
      frequencies in the skin blood flow power spectra of the ipsilateral but not of
      the contralateral hand. The greatest responses were found in the frequency range
      from 0.075 to 0.10 Hz. Therefore, these data indicate that the transmission from
      peripheral sympathetic nerves to cutaneous vascular smooth muscles in humans is
      slower than in rats. In addition, the frequency range believed to be most
      important in sympathetic modulation of vasomotor activity in humans corresponds
      to the frequency band of the greatest response of cutaneous vascular smooth
      muscle contraction to sympathetic nerve stimulation.

PMID- 9575933
TI  - Noradrenergic neurotransmission at PVN in locus ceruleus-induced baroreflex
      suppression in rats.
AB  - We investigated the role of ascending noradrenergic projections from the locus
      ceruleus (LC) to the paraventricular nucleus (PVN) of the hypothalamus in LC
      induced suppression of the baroreceptor reflex (BRR) response in adult Sprague
      Dawley rats maintained under pentobarbital anesthesia. On the basis of in vivo
      microdialysis and high-performance liquid chromatography-electrochemical
      detection, microinjection of L-glutamate (5 nmol) into the LC resulted in a site
      specific increase in norepinephrine (NE) concentration in the dialysate collected
      from the parvocellular subnucleus of the PVN. The temporal course of this
      increase in extracellular NE concentration in the PVN coincided with the time
      course of inhibition elicited by the LC on the BRR response. Microinfusion of NE
      (10, 50, or 100 nM) into the parvocellular subnucleus of the PVN by reverse
      microdialysis also promoted a parallel increase in NE at the PVN and a reduction
      in the BRR response. Inhibition of the BRR response induced by microinjection
      into the PVN of the alpha 1-adrenoceptor agonist phenylephrine (10 nmol) or
      chemical activation of the LC was reversed by bilateral PVN microinjection of
      prazosin (100 pmol). However, local application to the PVN of the alpha 2- or
      beta-adrenoceptor agonist guanabenz (10 nmol) or isoproterenol (10 nmol) was
      ineffective. Our results suggest that NE released from the LC-PVN noradrenergic
      projection may participate in LC-induced suppression of the BRR response by
      activating the alpha 1-adrenoceptors at the parvocellular subnucleus of the PVN.

PMID- 9575934
TI  - Incomplete global cerebral ischemia alters platelet biology in neonatal and adult
      sheep.
AB  - Platelets are implicated as etiologic agents in cerebral ischemia and as
      modulators of neural injury following an ischemic insult. We examined the effects
      of severe, transient global ischemia on platelet aggregation during 45-min
      ischemia and 30-, 60-, and 120-min reperfusion in adult and neonatal lambs. We
      also examined postischemic platelet deposition in brain and other tissues (120
      min reperfusion) using indium-111-labeled platelets. Ischemic cerebral blood flow
      fell to 5 +/- 1 and 5 +/- 2 ml.min-1.100 g-1 in lambs and sheep, respectively.
      During ischemia, platelet counts fell to 47.5 +/- 5.1% of control (P < 0.05) in
      lambs and 59 +/- 4.9% of control in sheep (P < 0.05). Ischemia depressed platelet
      aggregation response (P < 0.01) to 4 micrograms collagen in lambs and sheep (20.4
      +/- 29.2 and 26 +/- 44.7% of control, respectively). Marked platelet deposition
      occurred in brain and spleen in sheep, whereas significant platelet entrapment
      occurred only in brain in lambs. Our findings suggest that ischemia causes
      platelet activation and deposition in brain and noncerebral tissues.

PMID- 9575935
TI  - Vasomotor responses in chronically hyperperfused and hypoperfused rat mesenteric
      arteries.
AB  - We evaluated the reactivity of small arteries after remodeling induced by
      elevated or reduced blood flow. In 6-wk-old rats, every other first-order side
      branch of the superior mesenteric artery was ligated near the bifurcation of
      second-order branches. Four weeks after surgery, vessels that had been exposed to
      high flow (HF) or low flow (LF) were isolated and mounted in a pressure myograph
      at 100 mmHg and were compared with vessels from sham-operated rats (Sham). In HF:
      1) basal lumen diameter was increased; 2) sensitivity to norepinephrine, arginine
      vasopressin, and perivascular nerve stimulation was not modified; 3) maximal
      constrictor responses (delta diameter) to these stimuli and 125 mM K+ were
      increased; and 4) sensitivity and maximal dilator responses to sodium
      nitroprusside, acetylcholine, and flow were not modified. In LF: 1) basal
      diameter was reduced; 2) sensitivity to constrictor stimuli was not altered; 3)
      maximal responses to all vasoconstrictors except arginine vasopressin were
      reduced; and 4) sensitivity but not maximal dilator responses to sodium
      nitroprusside and acetylcholine was reduced. During acute flow-induced
      dilatations, lower shear stress was maintained in HF (48 +/- 7 dyn/cm2) than in
      Sham (63 +/- 10 dyn/cm2), but no shear stress regulation was observed in LF.
      These observations indicate that arterial structural responses to altered blood
      flow are accompanied by modified reactivity of the arterial smooth muscle, which
      entails changes in responsiveness to neurogenic and endothelium-dependent
      stimuli.

PMID- 9575936
TI  - Do beta 2-adrenergic receptors modulate Ca2+ in adult rat ventricular myocytes?
AB  - We examined the role of beta 2-adrenergic receptors (ARs) in modulating calcium
      homeostasis in rat ventricular myocytes. Zinterol (10 microM), an agonist with a
      25-fold greater affinity for beta 2-ARs over beta 1-ARs, modestly enhanced L-type
      calcium current (ICa) magnitude by approximately 30% and modestly accelerated the
      rate of Ca2+ concentration ([Ca2+]) decline (approximately 35%) but had little
      effect on the magnitude of the [Ca2+] transient (a nonsignificant 6% increase).
      However, 1 microM of the highly selective beta 1-AR antagonist CGP-20712A
      completely blocked the ICa increase induced by 10 microM zinterol. Pretreatment
      of cells with pertussis toxin (PTX) did not alter ICa enhancement by 10 microM
      zinterol, although it did abolish the ability of acetylcholine to block the
      forskolin-induced enhancement of ICa. Zinterol (10 microM) approximately doubled
      adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, although one-half of
      this increase was blocked by CGP-20712A. In contrast, 1 microM of the
      nonselective beta-agonist isoproterenol increased cAMP production 15-fold. Thus
      we found no evidence that activation of beta 2-ARs modulates calcium homeostasis
      in rat ventricular myocytes, even after treatment with PTX.

PMID- 9575937
TI  - Simplification of the quasiperiodic route to chaos in agonist-induced vasomotion
      by iterative circle maps.
AB  - We have shown that the patterns of vasomotion induced by histamine in isolated
      rabbit ear resistance arteries can be described in terms of iterative circle maps
      that model the dynamics of coupled nonlinear oscillators. Cyclopiazonic acid
      (CPA), an inhibitor of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase
      pump, consistently transformed chaotic behavior into characteristic periodic
      oscillations known as mixed-mode responses, which consist of mixtures of large-
      and small-amplitude excursions and represent frequency-locked states.
      Quasiperiodicity, which reflects the interaction of oscillators with
      incommensurate frequencies, was also observed, although in a smaller number of
      experiments. The patterns of mixed-mode complexes found at different CPA
      concentrations allowed the derivation of firing numbers, i.e., number of large
      oscillations/sum of number of small and large oscillations, and the sequences in
      which they emerged conformed to Farey arithmetic. Two-dimensional return maps
      derived by Poincare section of phase space representations of the dynamics were
      used to compute the mean number of rotations per iteration on the circle, i.e.,
      the winding number. Plots of winding number against firing number revealed a
      devil's staircase-type structure. Experiments with verapamil, a voltage-operated
      L-type Ca(2+)-channel antagonist, confirmed that influx of extracellular Ca2+ was
      essential to sustain chaos, quasiperiodicity, and mixed-mode responses. Nonlinear
      coupling between cytosolic and membrane events in rabbit ear arteries thus
      results in a self-organized dynamics that collapses to that predicted by the
      theory of simple circle maps.

PMID- 9575938
TI  - Pressure-permeability relationships in basement membrane: effects of static and
      dynamic pressures.
AB  - The glomerular basement membrane (GBM) is an important component of the
      filtration barrier that is the glomerular capillary wall. Previously GBM
      permeability has been investigated only under static pressures and often within a
      supraphysiological range. We used Matrigel as a model of GBM and formed membranes
      at the base of filtration chamber. We measured membrane permeability under static
      and dynamic pressures. Matrigel membranes were size and charge selective toward
      neutrally and negatively charged dextrans. Their permeability (as measured by
      hydraulic conductivity) was found to decrease from 1.61 +/- 0.06 to 0.75 +/- 0.07
      x 10(-6) cm.s-1.cmH2O-1 as static pressure increased from 6 to 78 cmH2O, an
      effect attributed to membrane compression. In comparison to static pressure,
      sinusoidal pressure waves with a mean pressure of 50 cmH2O decreased membrane
      permeability, e.g., fluid flux was reduced by a maximum of 2% to a value of 5.47
      +/- 0.38 x 10(-5) cm/s; albumin clearance was reduced by a maximum of 5.2% to a
      value of 9.63 +/- 1.06 x 10(-6) ml.cm-2.s-1. Such changes were affected by the
      frequency of pressure wave application and could be attributed to a switching on
      and off of the membrane compression effect.

PMID- 9575939
TI  - Cardiac myocyte calcium transport in phospholamban knockout mouse: relaxation and
      endogenous CaMKII effects.
AB  - Increases in heart rate are accompanied by acceleration of relaxation. This
      effect is apparent at the single myocyte level and depends on sarcoplasmic
      reticulum (SR) Ca transport and Ca/calmodulin dependent protein kinase [CaMKII;
      see R. A. Bassani, A. Mattiazzi, and D. M. Bers. Am. J. Physiol. 268 (Heart Circ.
      Physiol. 37): H703-H712, 1995]. Because phosphorylation of phospholamban (PLB) by
      CaMKII can stimulate SR Ca transport, it is a plausible candidate mechanism. We
      examined this issue using ventricular myocytes isolated from wild-type (WT) mice
      and those in which the PLB gene was ablated by gene targeting (PLB-KO). During
      steady-state (SS) stimulation, twitch relaxation and intracellular Ca
      concentration ([Ca]i) decline were significantly faster than after a rest in both
      WT and PLB-KO myocytes. Furthermore, the CaMKII inhibitor KN-93 (1 microM)
      abolished the stimulation-dependent acceleration of twitch [Ca]i decline in PLB
      KO. This indicates that neither PLB nor its phosphorylation are required for the
      CaMKII-dependent acceleration of the SS twitch [Ca]i decline and relaxation.
      Other quantitative aspects of Ca transport in WT and PLB-KO myocytes were also
      examined. As expected, the time constant (tau) of [Ca]i decline during the SS
      twitch is much faster in PLB-KO than in WT myocytes (112 +/- 6 vs. 188 +/- 14 ms,
      P < 0.0001). There was also an increase in SS SR Ca load, based on the change of
      [Ca]i during rapid caffeine-induced contractures (CafC) with Na/Ca exchange
      blocked (565 +/- 74 nM for WT, 1118 +/- 133 nM for PLB-KO, P < 0.01). Accounting
      for cytosolic Ca buffering, this implies a 37% increase in SR Ca content. The tau
      for [Ca]i decline of the cafC with Na present indicated slower extrusion by Na/Ca
      exchange in the PLB-KO mouse (2.2 +/- 0.2 s in WT vs. 3.2 +/- 0.2 in PLB-KO, P <
      0.01), although exchanger protein expression was unchanged. Integrated Ca flux
      analysis in WT and PLB-KO myocytes, respectively, shows that 90 and 96% of Ca
      during twitch relaxation is removed by the SR Ca-ATPase, 9 and 3.4% by Na/Ca
      exchange, and 0.5 and 0.1% by slow mechanisms (mitochondria Ca uniporter and
      sarcolemmal Ca-ATPase). We conclude that the PLB-KO myocytes retain a CaMKII
      dependent acceleration of SS twitch [Ca]i decline. The PLB-KO (vs. WT) myocytes
      also have higher SR Ca pump activity, higher SR Ca load, and reduced Na/Ca
      exchange activity.

PMID- 9575940
TI  - Ca flux, contractility, and excitation-contraction coupling in hypertrophic rat
      ventricular myocytes.
AB  - Left ventricular hypertrophy (approximately 40%) was induced in rats by banding
      of the abdominal aorta. After 16 wk, ventricular homogenates were prepared for
      biochemical measurements and ventricular myocytes were isolated for functional
      studies. In myocytes, the effects of banding on intracellular Ca handling,
      contraction, and excitation-contraction (E-C) coupling were determined using indo
      1 fluorescence and whole cell voltage clamp. After steady-state field or voltage
      clamp stimulation to load the sarcoplasmic reticulum (SR), SR Ca content assessed
      by caffeine-induced Ca transients was the same in sham and banded groups. Despite
      this, cell shortening amplitudes were significantly depressed in the banded
      group, suggesting altered contractile properties. In banded rats, the SR Ca
      adenosinetriphosphatase (Ca-ATPase) mRNA level was reduced, as was homogenate
      thapsigargin-sensitive SR Ca-ATPase, but cytosolic free Ca concentration ([Ca]i)
      decline attributed to SR Ca-ATPase activity in intact cells was not slowed.
      Banding also reduced Na/Ca exchange mRNA level but did not affect either Na
      dependent sarcolemmal 45Ca transport in homogenate or the rate of [Ca]i decline
      in intact cells attributed to Na/Ca exchange (during caffeine-induced
      contractures). Banding also did not change the rate of [Ca]i decline mediated by
      the combined function of the mitochondrial Ca uptake and sarcolemmal Ca-ATPase in
      intact cells. Ca current (ICa) density and voltage dependence were the same in
      sham and banded groups. Ryanodine receptor mRNA, protein content, and ryanodine
      affinity were also unchanged in the banded group. At 1 mM extracellular Ca
      concentration ([Ca]o), banding did not affect E-C coupling efficacy in intact
      cells under voltage clamp (i.e., same contraction for given ICa and SR Ca load).
      However, when [Ca]o was reduced to 0.5 mM, the efficacy of E-C coupling was
      greatly depressed in the banded group (even though ICa and SR Ca content were
      matched). In summary, unloaded myocyte contraction was depressed in these
      hypertrophic hearts, but Ca transport was little altered, at 1 mM [Ca]o. However,
      reduction of [Ca]o to 0.5 mM appears to unmask a depressed fractional SR Ca
      release in response to a given ICa trigger and SR Ca load.

PMID- 9575942
TI  - Correction of hypovolemic hypotension by centrally administered naloxone in
      conscious rabbits.
AB  - Our goal was to test directly whether the vasoconstrictor action of naloxone
      during hypovolemic hypotension is centrally mediated. In eight chronically
      instrumented rabbits, progressive central hypovolemia and fall in cardiac output
      (CO) were produced by gradually inflating a cuff on the thoracic vena cava.
      Central hypovolemia was then sustained for 8 min by holding CO constant. In the
      main experiment (n = 4), each rabbit was studied eight times over 4 experimental
      days. Saline or naloxone treatment commenced 10 min before progressive
      hypovolemia (early treatment) or 2 min after the onset of sustained hypovolemia
      (late treatment), given by intravenous infusion or into the fourth ventricle
      (V4). With saline treatment, there was spontaneous recovery of systemic
      vasoconstriction and arterial pressure during sustained hypovolemia. Late
      treatment with naloxone (4 mg/kg i.v.; 4-37 micrograms/kg V4) accelerated and
      exaggerated these changes. Thus, under conditions of constant CO and central
      blood volume, the vasodilatation of the decompensatory phase of acute hypovolemia
      is not sustained, and intravenous nalox one's vasoconstrictor action is via a
      brain stem mechanism.

PMID- 9575941
TI  - Effects of left ventricular hypertrophy on force and Ca2+ handling in isolated
      rat myocardium.
AB  - To study the effect of left ventricular (LV) hypertrophy on force and Ca2+
      handling in isolated rat myocardium, LV hypertrophy was induced in rats by
      banding of the abdominal aorta. After 16 wk, arterial pressure was assessed by
      catheterization. LV trabeculae were isolated and loaded with indo 1 salt by
      iontophoretic injection. Isometric force and intracellular free Ca2+
      concentration ([Ca2+]i) were measured at stimulation frequencies between 0.25 and
      3 Hz and rest intervals between 2 and 240 s. Sarcoplasmic reticulum (SR) Ca2+
      content was also investigated using rapid cooling contractures (RCC). Systolic
      and diastolic pressure as well as heart weight-to-body weight ratios were
      significantly elevated in banded compared with control animals (167 vs. 117 mmHg,
      108 vs. 83 mmHg, and 4.6 vs. 4.0 mg/g, respectively). At high frequencies, twitch
      relaxation and [Ca2+]i decline rates were significantly slower in banded compared
      with control rats, and diastolic [Ca2+]i was higher in the banded rat muscles (at
      3 Hz, force half-time = 83 vs. 68 ms; time constant of [Ca2+]i decline = 208 vs.
      118 ms; and diastolic [Ca2+]i = 505 vs. 353 nM). These differences could not be
      ascribed to altered Na+/Ca2+ exchange, since twitch relaxation and Ca2+ handling
      were not different between groups in the presence of caffeine (or cyclopiazonic
      acid plus ryanodine), where relaxation depends primarily on Na+/Ca2+ exchange.
      After long rest intervals (> or = 120 s), control rats showed a significant rest
      potentiation of force and Ca2+ transients, whereas banded rats did not. In
      addition, RCC amplitudes increased with rest in control but were unaltered in
      banded rats. In summary, pressure-overload hypertrophy was associated with slower
      twitch relaxation and [Ca2+]i decline but also with blunted rest potentiation of
      twitches and SR Ca2+ content of LV trabeculae. The decrease in SR Ca(2+)-ATPase
      function in banded rats may contribute to the observed diastolic dysfunction
      associated with pressure-overload hypertrophy.

PMID- 9575943
TI  - Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac
      arrest in infant piglets.
AB  - Using infant piglets, we studied the effects of nonspecific inhibition of nitric
      oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg) on
      vascular pressures, regional blood flow, and cerebral metabolism before 8 min of
      cardiac arrest, during 6 min of cardiopulmonary resuscitation (CPR), and at 10
      and 60 min of reperfusion. We tested the hypotheses that nonspecific NO synthase
      inhibition 1) will attenuate early postreperfusion hyperemia while still allowing
      for successful resuscitation after cardiac arrest, 2) will allow for
      normalization of blood flow to the kidneys and intestines after cardiac arrest,
      and 3) will maintain cerebral metabolism in the face of altered cerebral blood
      flow after reperfusion. Before cardiac arrest, L-NAME increased vascular
      pressures and cardiac output and decreased blood flow to brain (by 18%), heart
      (by 36%), kidney (by 46%), and intestine (by 52%) compared with placebo. During
      CPR, myocardial flow was maintained in all groups to successfully resuscitate 24
      of 28 animals [P value not significant (NS)]. Significantly, L-NAME attenuated
      postresuscitation hyperemia in cerebellum, diencephalon, anterior cerebral, and
      anterior-middle watershed cortical brain regions and to the heart. Likewise,
      cerebral metabolic rates of glucose (CMRGluc) and of lactate production (CMRLac)
      were not elevated at 10 min of reperfusion. These cerebral blood flow and
      metabolic effects were reversed by L-arginine. Flows returned to baseline levels
      by 60 min of reperfusion. Kidney and intestinal flow, however, remained depressed
      throughout reperfusion in all three groups. Thus nonspecific inhibition of NO
      synthase did not adversely affect the rate of resuscitation from cardiac arrest
      while attenuating cerebral and myocardial hyperemia. Even though CMRGluc and
      CMRLac early after resuscitation were decreased, they were maintained at baseline
      levels. This may be clinically advantageous in protecting the brain and heart
      from the damaging effects of hyperemia, such as blood-brain barrier disruption.

PMID- 9575945
TI  - Apparent arterial compliance.
AB  - Recently, there has been renewed interest in estimating total arterial
      compliance. Because it cannot be measured directly, a lumped model is usually
      applied to derive compliance from aortic pressure and flow. The archetypical
      model, the classical two-element windkessel, assumes 1) system linearity and 2)
      infinite pulse wave velocity. To generalize this model, investigators have added
      more elements and have incorporated nonlinearities. A different approach is taken
      here. It is assumed that the arterial system 1) is linear and 2) has finite pulse
      wave velocity. In doing so, the windkessel is generalized by describing
      compliance as a complex function of frequency that relates input pressure to
      volume stored. By applying transmission theory, this relationship is shown to be
      a function of heart rate, peripheral resistance, and pulse wave reflection.
      Because this pressure-volume relationship is generally not equal to total
      arterial compliance, it is termed "apparent compliance." This new concept forms
      the natural counterpart to the established concept of apparent pulse wave
      velocity.

PMID- 9575944
TI  - Physical basis of pressure transfer from periphery to aorta: a model-based study.
AB  - We propose a new method to derive aortic pressure from peripheral pressure and
      velocity by using a time domain approach. Peripheral pressure is separated into
      its forward and backward components, and these components are then shifted with a
      delay time, which is the ratio of wave speed and distance, and added again to
      reconstruct aortic pressure. We tested the method on a distributed model of the
      human systemic arterial tree. From carotid and brachial artery pressure and
      velocity, aortic systolic and diastolic pressure could be predicted within 0.3
      and 0.1 mmHg and 0.4 and 1.0 mmHg, respectively. The central aortic pressure wave
      shape was also predicted accurately from carotid and brachial pressure and
      velocity (root mean square error: 1.07 and 1.56 mmHg, respectively). The pressure
      transfer function depends on the reflection coefficient at the site of peripheral
      measurement and the delay time. A 50% decrease in arterial compliance had a
      considerable effect on reconstructed pressure when the control transfer function
      was used. A 70% decrease in arm resistance did not affect the reconstructed
      pressure. The transfer function thus depends on wave speed but has little
      dependence on vasoactive state. We conclude that central aortic pressure and the
      transfer function can be derived from peripheral pressure and velocity.

PMID- 9575946
TI  - A new method to measure regional myocardial time-varying elastance using minute
      vibration.
AB  - We developed a new technique to evaluate regional myocardial elastance using
      minute vibration. In 13 isolated cross-circulated canine hearts, we applied small
      sinusoidal vibrations of displacement to the left ventricular surface at various
      frequencies (50-100 Hz). Using the measured displacement and force between the
      vibrator head and myocardium, we derived myocardial elastance on the basis of the
      equation of motion for a given moment of the cardiac cycle. Simultaneous solution
      of the equations of motion at different frequencies yielded a unique value of
      elastance. Time-varying myocardial elastance increased from diastole (0.028 +/-
      0.211 x 10(6) dyn/cm) to systole (0.833 +/- 0.391 x 10(6) dyn/cm). The end
      systolic elastance (ees) linearly correlated with end-systolic left ventricular
      elastance (r = 0.717, P < 0.001) and also with the end-systolic Young's modulus
      (r = 0.874, P < 0.0001). We also measured ees at both ischemic and nonischemic
      regions during coronary occlusion. Young's modulus, estimated by normalizing ees
      by the wall thickness and by the estimated mass, did not change significantly at
      the nonischemic regions, whereas it decreased significantly from 2.303 +/- 0.556
      to 1.173 +/- 0.370 x 10(6) dyn/cm2 at the ischemic region after coronary
      occlusion (P < 0.005). We conclude that this technique is useful for the
      quantitative assessment of regional myocardial elastance.

PMID- 9575947
TI  - In vivo murine left ventricular pressure-volume relations by miniaturized
      conductance micromanometry.
AB  - The mouse is the species of choice for creating genetically engineered models of
      human disease. To study detailed systolic and diastolic left ventricular (LV)
      chamber mechanics in mice in vivo, we developed a miniaturized conductance
      manometer system. alpha-Chloralose-urethan-anesthetized animals were instrumented
      with a two-electrode pressure-volume catheter advanced via the LV apex to the
      aortic root. Custom electronics provided time-varying conductances related to
      cavity volume. Baseline hemodynamics were similar to values in conscious animals:
      634 +/- 14 beats/min, 112 +/- 4 mmHg, 5.3 +/- 0.8 mmHg, and 11,777 +/- 732 mmHg/s
      for heart rate, end-systolic and end-diastolic pressures, and maximum first
      derivative of ventricular pressure with respect to time (dP/dtmax), respectively.
      Catheter stroke volume during preload reduction by inferior vena caval occlusion
      correlated with that by ultrasound aortic flow probe (r2 = 0.98). This maneuver
      yielded end-systolic elastances of 79 +/- 21 mmHg/microliter, preload-recruitable
      stroke work of 82 +/- 5.6 mmHg, and slope of dP/dtmax-end-diastolic volume
      relation of 699 +/- 100 mmHg.s-1.microliter-1, and these relations varied
      predictably with acute inotropic interventions. The control normalized time
      varying elastance curve was similar to human data, further supporting comparable
      chamber mechanics between species. This novel approach should greatly help assess
      cardiovascular function in the blood-perfused murine heart.

PMID- 9575948
TI  - Development of ingestive behavior.
AB  - Swallowing represents a primary physiological function that provides for the
      ingestion of food and fluid. In precocial species, swallowing activity likely
      develops in utero to provide for a functional system during the neonatal period.
      The chronically instrumented ovine fetal preparation has provided the opportunity
      for recent advances in understanding the regulation of in utero swallowing
      activity. The near-term ovine fetus swallows fluid volumes (100-300 ml/kg) that
      are markedly greater, per body weight, than that of the adult (40-60 ml/kg).
      Spontaneous in utero swallowing and ingestive behavior contribute importantly to
      the regulation of amniotic fluid volume and composition, the acquisition and
      potential recirculation of solutes from the fetal environment, and the maturation
      of the fetal gastrointestinal tract. Fetal swallowing activity is influenced by
      fetal maturation, neurobehavioral state alterations, and the volume of amniotic
      fluid. Furthermore, intact dipsogenic mechanisms (osmolality, angiotensin II)
      have been demonstrated in the near-term ovine fetus. It remains unknown to what
      degree, if any, fetal swallowing may be influenced by nutrient appetite, salt
      appetite, or taste. Nevertheless, the development of dipsogenic and additional
      regulatory mechanisms for ingestive behavior occurs during fetal life and may be
      susceptible to changes in the pregnancy environment. This review describes what
      is currently known regarding the in utero development of ingestive behavior and
      the importance of this activity for fetal and perhaps ultimately adult fluid
      homeostasis.

PMID- 9575949
TI  - Effects of increased fat availability on fat-carbohydrate interaction during
      prolonged exercise in men.
AB  - The study examined the existence and regulation of fat-carbohydrate interaction
      during low- and moderate-intensity exercise. Eight males cycled for 10 min at 40%
      and 60 min at 65% maximal O2 uptake (VO2max) while infused with either Intralipid
      and heparin (Int) or saline (Con). Before exercise, plasma arterial free fatty
      acid (FFA) was 0.69 +/- 0.04 mM (Int) vs. 0.25 +/- 0.04 mM (Con). Muscle biopsies
      were taken at rest and at 10, 20, and 70 min of exercise. Arterial and femoral
      venous blood samples and expired gases were collected simultaneously throughout
      exercise, and blood flow was estimated from pulmonary O2 uptake and the leg
      arterial-venous O2 difference. Respiratory exchange ratio was higher in Con (0.94
      +/- 0.01) compared with Int (0.91 +/- 0.01). Mean net leg FFA uptake was higher
      in Int (0.16 +/- 0.03 vs. 0.04 +/- 0.01 mmol/min), and net lactate efflux was
      reduced (Int, 1.55 +/- 0.36 vs. Con, 3.07 +/- 0.47 mmol/min). Leg net glucose
      uptake was unaffected by Int. Muscle glycogen degradation was 23% lower in Int
      [230 +/- 29 vs. 297 +/- 36 mmol glucosyl units/kg dry muscle (dm)]. Pyruvate
      dehydrogenase activity in the a form (PDHa) was lower during Int (1.61 +/- 0.17
      vs. 2.22 +/- 0.24 mmol.min-1.kg wet muscle-1), and muscle citrate was higher
      (0.59 +/- 0.04 vs. 0.48 +/- 0.04 mmol/kg dm). Muscle lactate, phosphocreatine,
      ATP, acetyl-CoA, acetyl-carnitine, and P(i) were unaffected by Int. Calculated
      free AMP was significantly lower in Int compared with Con at 70 min of exercise
      (3.3 +/- 0.8 vs. 1.5 +/- 0.3 mumol/kg dm). The high FFA-induced reduction in
      glycogenolysis and carbohydrate oxidation at 65% VO2max appears to be due to
      regulation at several sites. The reduced flux through phosphorylase and
      phosphofructokinase during Int may have been due to reduced free AMP accumulation
      and increased cytoplasmic citrate. The mechanism for reduced PDH transformation
      to the a form is unknown but suggests reduced flux through PDH.

PMID- 9575950
TI  - Neurosteroid modulation of arterial baroreflex-sensitive neurons in rat rostral
      ventrolateral medulla.
AB  - The major metabolite of progesterone, 3 alpha-OH-dihydroprogesterone (3 alpha-OH
      DHP), is the most potent endogenous positive modulator of central nervous system
      GABAA receptors. Acute intravenous administration of 3 alpha-OH-DHP to virgin
      female rats potentiates arterial baroreflex sympathoinhibitory responses. The
      current experiments tested the possibility that circulating 3 alpha-OH-DHP
      potentiates central GABAergic influences in the rostral ventrolateral medulla
      (RVLM). The unit activity of spontaneously active, spinally projecting, and
      arterial pressure-sensitive neurons was recorded in the RVLM of urethan
      anesthetized rats. Arterial pressure sensitivity of RVLM neurons was tested
      before (control) and 10 min after bolus injection (44 microliters i.v.) of 3
      alpha-OH-DHP (1.12 micrograms/kg, n = 19) or vehicle (40% beta-cyclodextrin, n =
      8). Both threshold pressure and saturation pressure for inhibition of RVLM
      neurons were decreased after acute administration of a physiological dose of 3
      alpha-OH-DHP (1.12 micrograms/kg i.v.), which produces plasma concentrations
      similar to those seen during pregnancy (20-30 ng/ml), suggesting potentiated
      responsiveness to endogenously released GABA. Following suppression by 3 alpha-OH
      DHP, high doses of the inactive stereoisomer 3 beta-OH-DHP (112-224 micrograms/kg
      i.v.; n = 8) restored unit activity, presumably by displacing 3 alpha-OH-DHP from
      the neurosteroid binding site on GABAA receptors.

PMID- 9575951
TI  - IGF-I alters lymphocyte survival and regeneration in thymus and spleen after
      dexamethasone treatment.
AB  - Insulin-like growth factor I (IGF-I) is a growth factor for the immune system,
      increasing lymphocyte number and function via greater lymphocyte generation
      and/or survival. We investigated the effects of IGF-I on lymphocyte survival and
      regeneration in the thymus and spleen after dexamethasone (Dex) treatment in rats
      maintained with parenteral nutrition and given recombinant human IGF-I (800
      micrograms/day) for 12 h, 48 h, and 5 days. IGF-I did not prevent Dex-induced
      apoptosis of thymocytes but reduced cell death in the spleen at 12 and 48 h. IGF
      I exerted a modest protective effect (10-15% reduction in cell loss) on all
      splenic T and B cell subsets examined by flow cytometry. IGF-I enhanced recovery
      of CD4+8+ immature T cells in the thymus and decreased the proportion of CD8+
      (cytotoxic/suppressor) T cells in the spleen. In rats not treated with Dex, IGF-I
      significantly increased total lymphocyte number and the number of CD4+8+ T cells
      in thymus and spleen. Our results suggest that IGF-I may alter homeostasis in the
      immune system by modulating lymphocyte generation and survival.

PMID- 9575952
TI  - Contribution of hypercapnia and trigeminal stimulation to cerebrovascular
      dilation during simulated diving.
AB  - We investigated the relative contribution of humoral (carbon dioxide) and neural
      (trigeminal stimulation) inputs in the cerebrovasodilatory response to simulated
      diving in the rat. The cerebral hemodynamic profile of rats was determined using
      the brain blood flow tracer N-[14C]isopropyl-p-iodoamphetamine. During a
      simulated dive response, cerebral vascular resistance (CVR) decreased 63.1%,
      resulting in a 1.5-fold increase in cerebral blood flow (CBF). To investigate the
      contribution of hypercapnia to the decrease in CVR during simulated diving, we
      measured CBF during simulated diving in rats with preexisting hypocapnia. To
      investigate the contribution of trigeminal input, we measured CBF during periods
      of trigeminal stimulation alone with continued ventilation. Preexisting
      hypocapnia abolished the cerebrovasodilatory response to simulated diving.
      Trigeminal stimulation alone did not produce a significant increase in CBF from
      control values in any brain region, suggesting that trigeminal input does not
      contribute to the cerebrovascular response to simulated diving in rats. These
      results suggest that the cerebrovasodilatory response observed during diving in
      small mammals is driven primarily by progressive hypercapnia associated with
      asphyxia.

PMID- 9575953
TI  - Prevention of reflex natriuresis after acute unilateral nephrectomy by
      melanocortin receptor antagonists.
AB  - gamma-Melanocyte-stimulating hormone (gamma-MSH), atrial natriuretic peptide
      (ANP), and oxytocin have been identified as candidate hormonal mediators of the
      reflex natriuresis that follows acute unilateral nephrectomy (AUN).
      Pharmacological characterization of the third melanocortin receptor (MC3-R)
      indicates that it uniquely responds to physiological concentrations of gamma-MSH.
      We tested the roles of gamma-MSH, ANP, and oxytocin in the postnephrectomy
      natriuresis by carrying out AUN during continuous intrarenal infusion of specific
      antagonists for their cognate receptors. In anesthetized Sprague-Dawley rats,
      urinary sodium excretion (UNaV) increased from 0.34 +/- 0.04 to 1.12 +/- 0.11 mu
      eq/min 90 min after AUN (P < 0.001). No change in UNaV occurred in rats
      undergoing a sham AUN procedure. Plasma immunoreactive gamma-MSH concentration
      was 53 +/- 8 fmol/ml after sham AUN but 112 +/- 17 fmol/ml after AUN (P < 0.01).
      SHU-9119 and SHU-9005 are substituted derivatives of alpha-MSH with potent
      antagonism at the MC3-R in vitro. Infusion of these compounds at 5 pmol/min
      completely blocked the natriuretic response to AUN despite a similar elevation in
      plasma gamma-MSH (111 +/- 12 vs. 49 +/- 8 fmol/ml in sham rats, P < 0.01).
      Intrarenal infusion of the ANP receptor antagonist A-71915 (5 pmol/min) or the
      oxytocin receptor antagonist [d(CH2)(5)1, Tyr(Me)2,Orn8] vasotocin (10 pmol/min)
      effectively inhibited the natriuresis induced by intravenous infusion of ANP or
      oxytocin (each at 1 pmol/min), respectively, but did not block the natriuresis
      after AUN. Plasma immunoreactivity of these peptides was not increased after AUN.
      These results indicate that reflex natriuresis after AUN is accompanied by an
      increase in plasma gamma-MSH but not ANP or oxytocin concentration and is
      prevented by intrarenal infusion of receptor antagonists with selectivity for MC3
      R. The data indicate that gamma-MSH or a closely related peptide mediates
      postnephrectomy natriuresis and provide further support for the possibility that
      gamma-MSH may play a wider role in sodium homeostasis.

PMID- 9575954
TI  - Differential selectivity of cardiac neurons in separate intrathoracic autonomic
      ganglia.
AB  - Analyses of activity generated by neurons in middle cervical or stellate ganglia
      versus intrinsic cardiac ganglia were performed to determine how neurons in
      different intrathoracic ganglia, which are involved in cardiac regulation,
      interact. Discharges of 19% of intrathoracic extracardiac neurons and 32% of
      intrinsic cardiac neurons were related to cardiodynamics. Epicardial touch
      increased the activity generated by approximately 80% of intrinsic cardiac
      neurons and approximately 60% of extracardiac neurons. Both populations responded
      similarly to epicardial chemical stimuli. Activity generated by neurons in
      intrinsic cardiac ganglia demonstrated no consistent short-term relationships to
      neurons in extracardiac ganglia. Myocardial ischemia influenced extracardiac and
      intrinsic cardiac neurons similarly. Carotid artery baroreceptors influenced
      neurons in ipsilateral extracardiac ganglia. After decentralization from the
      central nervous system, intrinsic cardiac neurons received afferent inputs
      primarily from cardiac chemosensitive neurites, whereas middle cervical ganglion
      neurons received afferent inputs primarily from cardiac mechanosensory neurites.
      It is concluded that the populations of neurons in different intrathoracic
      ganglia can display differential reflex control of cardiac function. Their
      redundancy in function and noncoupled behavior minimizes cardiac dependency on a
      single population of intrathoracic neurons.

PMID- 9575955
TI  - Behaviors of hypoglossal hyoid motoneurons in laryngeal and vestibular reflexes
      and in deglutition and emesis.
AB  - Reflex responses of hypoglossal motoneurons innervating the geniohyoid (GH) and
      thyrohyoid (TH) muscles from the superior laryngeal (SLN) and vestibular nerves
      and their behaviors during fictive swallowing and vomiting were examined by
      recording both the extracellular activities of 11 single cells in the hypoglossal
      nucleus and GH and TH muscle nerve activity in eight decerebrate, paralyzed, and
      artificially ventilated cats. The majority of TH motoneurons were either active
      and/or exhibited shortened antidromic latencies during early expiration. In
      contrast, GH motoneurons did not exhibit any respiratory-related activity.
      Electrical single-shock stimulation of the SLN never evoked an excitatory reflex
      response on GH or TH motoneurons but rather evoked inhibitory responses on the
      THs. Unlike other hypoglossal motoneurons, GH and TH motoneurons do not appear to
      receive vestibular inputs. However, they can exhibit robust activities during
      fictive swallowing and vomiting, particularly during expulsion. Thus these
      motoneurons may play an important role in airway protection during swallowing and
      vomiting but not in controlling upper airway patency regulated by vestibular
      afferents.

PMID- 9575956
TI  - Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and
      sepsis.
AB  - Inflammatory cytokines may mediate the host response to infection via central
      nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms.
      Previous studies have shown that intravenous administration of interleukin (IL)-1
      beta alters the concentration of the anabolic hormone insulin-like growth factor
      (IGF)-I in plasma and various tissues. The purpose of the present study was to
      determine 1) whether the intracerebroventricular injection of IL-1 beta can
      influence peripheral IGF-I levels in control animals and 2) whether the central
      administration of a IL-1 receptor antagonist (IL-1ra) can prevent the changes in
      peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis
      produced by cecal ligation and puncture. In the first experiment, injection of IL
      1 beta (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius
      muscle 28-36% by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at
      3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus,
      kidney, spleen, intestine, or whole brain after IL-1 beta. In the second series
      of experiments, LPS injected intravenously decreased IGF-I levels in plasma,
      liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and
      6 h in these tissues (59, 57, and 48%, respectively). Moreover, the IGF-I content
      was also decreased in soleus (30-35%) and increased in kidney (2- to 3-fold)
      after LPS. In the third experiment, changes in IGF-I levels in plasma and
      tissues, similar to those seen in LPS-treated rats, were detected 24 h after
      induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not
      alter any of the changes in IGF-I produced by either LPS or sepsis, although it
      did attenuate the concomitant changes in growth hormone levels. These data
      suggest that, although central IL-1 beta is capable of modulating peripheral IGF
      I levels, central administration of IL-1ra was unable to modulate the changes in
      peripheral IGF-I in blood and tissues produced by either endotoxemia or
      peritonitis.

PMID- 9575957
TI  - Seasonal differences in resting oxygen consumption, respiratory quotient, and
      free thyroxine in woodchucks.
AB  - The relationships among seasonal differences in body weight, food intake,
      metabolism, and thyroid hormone in woodchucks were investigated in 12 woodchucks.
      Six woodchucks had been maintained on a photoperiod simulating that found at 42
      degrees N (boreal woodchucks). The other group of six animals had been maintained
      similarly in all respects except that the light simulated that found at 42
      degrees S (austral woodchucks). An openflow respirometer, calibrated using the N2
      dilution method, was used to determine metabolism twice in a 2-wk period near the
      September equinox, while at the same time food intake, body weight, and free
      thyroxine concentrations (fT4) were measured. Body weight was the same for both
      groups of woodchucks. However, compared with boreal animals near their autumnal
      equinox, austral woodchucks near their vernal equinox had significantly higher (P
      < 0.01) daily food intake (5 +/- 2 vs. 35 +/- 2 g.kg-1.day-1), oxygen consumption
      (4.4 +/- 0.3 vs. 7.3 +/- 0.3 ml.min-1.kg-1), carbon dioxide production (2.8 +/-
      0.2 vs. 6.0 +/- 0.2 ml.min-1.kg-1), respiratory quotient (0.65 +/- 0.01 vs. 0.82
      +/- 0.02), and fT4 (0.21 +/- 0.01 vs. 0.65 +/- 0.05 ng/dl). It was concluded that
      photoperiod has a strong effect on resting metabolism in the woodchuck and that
      there is an association between fT4 and changes in food intake and metabolic
      rate.

PMID- 9575958
TI  - Hemodynamic effect of 17 beta-estradiol in absence of NO in ovariectomized rats:
      role of angiotensin II.
AB  - Previous reports correlate plasma levels of estrogen with increased nitric oxide
      (NO) production. To investigate whether the hemodynamic effects of estrogens are
      mediated by NO, we compared the hemodynamic changes induced by 17 beta-estradiol
      (100 micrograms/kg) in the absence and presence of the NO synthesis inhibitor N
      omega-nitro-L-arginine methyl ester (L-NAME). All protocols were performed in
      ovariectomized, conscious rats. Estradiol alone resulted in no significant
      changes in cardiac index (CI) or mean arterial pressure (MAP). However, in the
      presence of L-NAME, estradiol induced a significant increase in total peripheral
      resistance (TPR) of 37.3 +/- 11.7% and a decrease in CI of 27 +/- 4.9%, without
      changes in MAP. Previous blockade of angiotensin II AT1 receptors with losartan
      prevented any change in CI and TPR induced by 17 beta-estradiol in the presence
      of L-NAME. These observations suggest that NO is necessary to offset a
      vasoconstrictor action of angiotensin II, which is stimulated by estradiol
      administration.

PMID- 9575959
TI  - Central actions of adrenomedullin on cardiovascular parameters and sympathetic
      outflow in conscious rats.
AB  - Adrenomedullin (ADM) is reported to be a peripherally acting hypotensive peptide,
      but its central actions are unclear. We investigated the effects of centrally
      administered ADM on blood pressure (BP), heart rate (HR), and renal sympathetic
      nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. We
      also investigated the receptors interacting with ADM using two putative
      antagonists. Intracerebroventricular administration of ADM in doses of 0.1 and
      0.5 nmol/kg caused tachycardia and early inhibition of RSNA. Central ADM (1.0
      nmol/kg) induced hypertension, tachycardia, and a decrease followed by an
      increase in RSNA. In SAD rats, increases in BP, HR, and RSNA at the late phase
      were enhanced by central ADM (1.0 nmol/kg), whereas the early decrease in RSNA
      remained. Thus the inhibition of RSNA via central ADM may be unrelated to the
      arterial baroreceptor reflex. Pretreatment with antagonists human calcitonin gene
      related peptide-(8-37) and human ADM-(22-52) significantly suppressed the central
      actions of ADM. The findings suggest that ADM is involved as a neuropeptide in
      the receptor-mediated central regulation of the cardiovascular system and RSNA.

PMID- 9575960
TI  - Heterozygosity for Lep(ob) or Lep(rdb) affects body composition and leptin
      homeostasis in adult mice.
AB  - In an effort to understand the genetics of human obesity, we have studied the
      physiology and molecular genetics of rodent models with monogenetic forms of
      obesity including the leptin gene-defective (Lep(ob)/Lep(ob)) and leptin receptor
      gene-defective (Lep(rdb)/Lep(rdb)) mouse. In the experiments reported here, we
      investigated the effects of heterozygosity at Lep(ob) and Lep(rdb) on body
      composition and circulating leptin concentration in +/+, Lep(rdb)/+, and
      Lep(ob)/+ adult mice to identify possible gene dosage effects of these mutations
      that might elucidate their physiology. Adult mice heterozygous for the Lep(ob) or
      Lep(rdb) allele had equivalent fat mass and percentage body fat, which was
      increased 27-47% and 23-35%, respectively, relative to +/+ littermates. Plasma
      leptin concentrations adjusted for fat mass were 6.5 ng/ml in the Lep(ob)/+, 9.6
      ng/ml in the +/+, and 11.5 ng/ml in the Lep(rdb)/+ mice. Sex had no effect on
      plasma leptin after controlling for fat mass. These data, and data from a small
      number of mice heterozygous at both Lep(ob) and Lep(rdb) (compound
      heterozygotes), suggest that leptin protein produced per mass of body fat is
      reduced in Lep(ob)/+ mice and that body fat is increased in Lep(ob)/+ mice until
      plasma leptin concentrations reach that of a normal +/+ mouse. The elevated
      plasma leptin concentration in the Lep(rdb)/+ mice suggests that LEPR may mediate
      autocrine suppression of Lep expression. These results raise the possibility that
      human mutations that have even subtle effects on the leptin/leptin receptor
      system in either the homozygous or heterozygous state may have significant
      effects on adiposity.

PMID- 9575961
TI  - Nonphotic entrainment of the human circadian pacemaker.
AB  - In organisms as diverse as single-celled algae and humans, light is the primary
      stimulus mediating entrainment of the circadian biological clock. Reports that
      some totally blind individuals appear entrained to the 24-h day have suggested
      that nonphotic stimuli may also be effective circadian synchronizers in humans,
      although the nonphotic stimuli are probably comparatively weak synchronizers,
      because the circadian rhythms of many totally blind individuals "free run" even
      when they maintain a 24-h activity-rest schedule. To investigate entrainment by
      nonphotic synchronizers, we studied the endogenous circadian melatonin and core
      body temperature rhythms of 15 totally blind subjects who lacked conscious light
      perception and exhibited no suppression of plasma melatonin in response to ocular
      bright-light exposure. Nine of these fifteen blind individuals were able to
      maintain synchronization to the 24-h day, albeit often at an atypical phase angle
      of entrainment. Nonphotic stimuli also synchronized the endogenous circadian
      rhythms of a totally blind individual to a non-24-h schedule while living in
      constant near darkness. We conclude that nonphotic stimuli can entrain the human
      circadian pacemaker in some individuals lacking ocular circadian photoreception.

PMID- 9575962
TI  - Tonic neurogenic inhibition of interleukin-6 secretion from murine spleen caused
      by opioidergic transmission.
AB  - The peripheral nervous system and the immune system were shown to have
      neurohumoral interactions. This study extends observations that demonstrated
      neuronal modulation of spontaneous interleukin-6 (IL-6) secretion in the spleen
      by norepinephrine (NE) and beta-endorphin. Spontaneous IL-6 secretion in vivo was
      markedly reduced by removal of macrophages with the clodronate technique.
      Furthermore, spontaneous IL-6 secretion was significantly inhibited at
      physiological concentrations of cortisol (10(-7) M). In the presence of 10(-7) M
      cortisol, addition of norepinephrine (NE; 10(-5) M) and isoproterenol (10(-6) and
      10(-5) M) significantly increased spontaneous IL-6 secretion (+20%; P = 0.0280, P
      = 0.0005, and P = 0.0050, respectively). In contrast, addition of beta-endorphin
      significantly inhibited spontaneous IL-6 secretion in the presence of 10(-7) M
      cortisol (-40%; 10(-11) M, P = 0.0410; 10(-10) M, P = 0.0005). To study the
      effect of endogenously released transmitters on spontaneous IL-6 secretion,
      spleen slices were electrically stimulated with 1, 5, 10, 50, and 100 Hz.
      Spontaneous IL-6 secretion was markedly reduced at a frequency of 10 Hz with 10(
      7) M cortisol present (P < 0.0001). This indicates that the combination of nerve
      firing at 5-10 Hz and physiological cortisol conditions inhibits spontaneous IL-6
      secretion. Inhibition of spontaneous IL-6 secretion from spleen macrophages is
      most probably due to a net inhibitory effect of opioidergic transmission under
      these conditions.

PMID- 9575963
TI  - Seasonality and role of SCN in entrainment of lizard circadian rhythms to daily
      melatonin injections.
AB  - To establish whether the capability of daily melatonin injections to entrain
      circadian rhythms varies with season, we examined in constant conditions the
      locomotor behavior of lizards Podarcis sicula collected and subjected to daily
      melatonin injections at different times of the year. Although in summer locomotor
      rhythms of both pineal-intact and pinealectomized lizards became entrained to the
      24-h injection period, in the other seasons their rhythms did not entrain to the
      injection period. To establish whether the suprachiasmatic nuclei (SCN) mediate
      summer entrainment of locomotor rhythms to melatonin, we examined the behavioral
      effects of daily melatonin injections in lizards subjected to either bilateral
      (SCN-X) or unilateral (USCN-X) ablation of the SCN. SCN-X lizards became
      behaviorally arrhythmic, and daily melatonin injections did not restore
      rhythmicity. USCN-X lizards remained rhythmic, and their locomotor rhythms did
      entrain to the injections. Besides demonstrating for the first time in a
      vertebrate that daily melatonin injections are capable of entraining circadian
      rhythmicity in only one season (summer), the present results support the view
      that the SCN (and not the pineal gland) are the primary target sites of melatonin
      in the circadian system of P. sicula.

PMID- 9575964
TI  - Discharge patterns of Botzinger complex neurons during cough in the cat.
AB  - This study was carried out on pentobarbital sodium-anesthetized, spontaneously
      breathing cats to address the hypothesis that Botzinger complex (BotC) neurons
      are involved in the production of the cough motor pattern induced by mechanical
      stimulation of the tracheobronchial tree. Phrenic nerve and abdominal muscle
      activities as well as intratracheal pressure were monitored; single-unit
      extracellular recordings from BotC neurons (n = 87) were performed. The majority
      of augmenting expiratory (E-Aug) neurons encountered (n = 47) displayed
      excitatory responses during the expulsive phases of coughing in parallel with the
      main components of the abdominal bursts and the corresponding increases in
      tracheal pressure. We also encountered E-Aug neurons markedly depressed up to
      complete inhibition during coughing (n = 14) as well as E-Aug neurons assuming a
      decremental pattern without any increase or even with some reduction in their
      peak activity (n = 15). During the expiratory thrusts, most decrementing
      expiratory neurons (n = 7) presented excitatory responses, whereas others were
      depressed (n = 3) or completely inhibited (n = 1). The results are consistent
      with the view that these neurons are involved in the generation of the cough
      motor pattern and, in particular, that some BotC E-Aug neurons convey excitatory
      drive to caudal expiratory neurons and, hence, to expiratory motoneurons.

PMID- 9575965
TI  - Interindividual variation in total and carrier-mediated lactate influx into red
      blood cells.
AB  - To study in standardbred horses interindividual variation in the influx of
      lactate into red blood cells, venous blood samples were collected from 89 horses
      from 2 wk to 9 yr of age. For 62 horses, the rate of influx was normally
      distributed with a mean rate of 4.09 nmol.mg protein-1.min-1 at a lactate
      concentration of 10 mM, and the respective value for the other 27 horses was 0.58
      nmol.mg protein-1.min-1. At 30 mM of lactate, the rates were 8.71 and 1.97
      nmol.mg protein-1.min-1, respectively. This bimodal distribution was independent
      of age. In horses with high transport activity, the monocarboxylate transporter
      (MCT) appears to be the major carrier, whereas, in those with low transport
      activity, no activity of the MCT could be detected. The band 3 protein may
      account for 18-39% of transport activity. With all age groups combined, the
      transport activity tended to be higher in mares than in stallions. Lactate
      transport into red blood cells seems thus to be an inherent property in which
      participation of various transporters varies interindividually.

PMID- 9575966
TI  - Functional role of ecto-ATPase activity in goldfish hepatocytes.
AB  - Extracellular [gamma-32P]ATP added to a suspension of goldfish hepatocytes can be
      hydrolyzed to ADP plus gamma-32Pi due to the presence of an ecto-ATPase located
      in the plasma membrane. Ecto-ATPase activity was a hyperbolic function of ATP
      concentration ([ATP]), with apparent maximal activity of 8.3 +/- 0.4 nmol
      P(i).(10(6) cells)-1.min-1 and substrate concentration at which a half-maximal
      hydrolysis rate is obtained of 667 +/- 123 microM. Ecto-ATPase activity was
      inhibited 70% by suramin but was insensitive to inhibitors of transport ATPases.
      Addition of 5 microM [alpha-32P]ATP to the hepatocyte suspension induced the
      extracellular release of alpha-32P(i) [8.2 pmol.(10(6) cells)-1.min-1] and
      adenosine, suggesting the presence of other ectonucleotidase(s). Exposure of cell
      suspensions to 5 microM [2,8-3H]ATP resulted in uptake of [2,8-3H]adenosine at
      7.9 pmol.(10(6) cells)-1.min-1. Addition of low micromolar [ATP] strongly
      increased cytosolic free Ca2+ (Ca2+i). This effect could be partially mimicked by
      adenosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable analog of ATP. The
      blockage of both glycolysis and oxidative phosphorylation led to a sixfold
      increase of Ca2+i and an 80% decrease of intracellular ATP, but ecto-ATPase
      activity was insensitive to these metabolic changes. Ecto-ATPase activity
      represents the first step leading to the complete hydrolysis of extracellular
      ATP, which allows 1) termination of the action of ATP on specific purinoceptors
      and 2) the resulting adenosine to be taken up by the cells.

PMID- 9575967
TI  - Hormonally controlled chloride movement across Drosophila tubules is via ion
      channels in stellate cells.
AB  - Anion conductance across the Drosophila melanogaster Malpighian (renal) tubule
      was investigated by a combination of physiological and transgenic techniques.
      Patch-clamp recordings identified clusters of 4, 4'-diisothiocyanostilbene-2,2'
      disulfonic acid (DIDS)-sensitive "maxi-chloride" channels in a small domain of
      the apical membrane. Fluid secretion assays demonstrated sensitivity to the
      chloride channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid,
      diphenylamine-2-carboxylate, anthracene-9-carboxylic acid, and niflumic acid.
      Electrophysiological analysis showed that the calcium-mediated increase in anion
      conductance was blocked by the same agents. Vibrating probe analysis revealed a
      small number of current density hot spots, coincident with "stellate" cells, that
      were abolished by low-chloride saline or the same chloride channel blockers. GAL
      4-targeted expression of an aequorin transgene revealed that the neurohormone
      leucokinin elicits a rapid increase in intracellular calcium levels in stellate
      cells that precedes the fastest demonstrable physiological effect. Taken
      together, these data show that leucokinins act on stellate cells through
      intracellular calcium to increase transcellular chloride conductance through
      channels. As electrogenic cation conductance is confined to principal cells, the
      two pathways are spatially segregated in this tissue.

PMID- 9575968
TI  - A prostaglandin, not NO, mediates endothelium-dependent dilation in ventral aorta
      of shark (Squalus acanthias).
AB  - In mammals, the vascular endothelium releases a variety of paracrine factors,
      including the vasodilatory prostaglandin (PG)I2 and nitric oxide (NO), which is
      generally accepted as the major endothelium-derived relaxing factor (EDRF) in
      mammals. Current evidence for the vascular NO-EDRF system in fishes is
      contradictory. In addition, the role of PGs in the control of fish vascular
      tension is also unclear. We have utilized isolated rings of the ventral aorta of
      the spiny dogfish shark to examine the ability of various components of the NO
      system to dilate this vessel. Neither the NO precursor L-arginine, the NO donor
      sodium nitroprusside, nor NO itself dilated the rings. The Ca2+ ionophore A-23187
      did produce an endothelium-dependent dilation that was not inhibited by the NO
      synthase inhibitor NG-nitro-L-arginine methyl ester but was inhibited by the
      cyclooxygenase inhibitor indomethacin, suggesting that PGs are involved. PGE1 and
      carbaprostacyclin, but not PGI2, produced concentration-dependent dilation, and
      intact aortic rings secreted five times as much PGI2 as PGE in both the
      unstimulated state and after stimulation with A-23187. Our data suggest strongly
      that a PG, most probably PGI2, is the EDRF in the ventral aorta of this shark
      species.

PMID- 9575970
TI  - Roles of cardiac output and peripheral resistance in mediating blood pressure
      response to stress in rats.
AB  - The change in arterial blood pressure (BP) in response to presentation of an
      acute behavioral stress (i.e., classical conditioning) in rat includes an initial
      rapid rise (C1) followed by a delayed, but more sustained, pressor response (C2).
      The purpose of this experiment is to determine the patterns of change in cardiac
      output (CO) and total peripheral vascular resistance (TPR) that are associated
      with the behaviorally induced pressor response. A blood flow probe was implanted
      around the ascending aorta, and a catheter was implanted in a femoral artery in
      10 male Sprague-Dawley rats. The rats were trained by a 15-s tone (CS+) followed
      by a 0.5-s tail shock; another tone (CS-), never followed by shock, served as a
      behavioral control. BP responded to the stressful stimulus (CS+) by a rapid C1
      increase (8 +/- 1 mmHg; mean +/- SE) followed by the delayed C2 response (2 +/-
      0.3 mmHg); the unconditioned response to shock was a 9 +/- 2 mmHg increase in BP.
      The C1 BP increase produced a significant increase in TPR (10 +/- 1 dyn.s/cm5);
      CO was not significantly changed. TPR decreased during C2 (-4 +/- 2 dyn.s/cm5),
      whereas CO was significantly increased (2 +/- 1 ml/min). These data contribute to
      our understanding of how the autonomic nervous system organizes the
      cardiovascular response to a suddenly perceived behavioral stress.

PMID- 9575969
TI  - Chloroquine inhibits proinflammatory cytokine release into human whole blood.
AB  - Excessive synthesis and release of proinflammatory cytokines during endotoxemia
      causes severe pathophysiological derangements and organ failure. Because the
      lysosomotropic agent chloroquine has been effective in the treatment of diseases
      associated with increased secretion of proinflammatory cytokines such as malaria
      or rheumatoid arthritis, this study evaluates the potential effect of chloroquine
      on endotoxin-induced cytokinemia using human whole blood from healthy volunteers.
      Chloroquine revealed a dose-dependent inhibitory effect on endotoxin-induced
      secretion of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6
      that was associated with reduced cytokine mRNA expression. Moreover, ammonia and
      methylamine, which react as weak bases like chloroquine, reduced synthesis and
      secretion of proinflammatory cytokines. These data indicate a potent anti
      inflammatory effect of chloroquine on endotoxin-induced synthesis of
      proinflammatory cytokines that may be due to its weak base effect. Thus
      chloroquine may be of therapeutic benefit not only, during chronic inflammation
      but also in diseases that are related to bacteria-induced inflammation.

PMID- 9575971
TI  - Effects of L-NAME on cerebral metabolic, vasopressin, oxytocin, and blood
      pressure responses in hemorrhaged rats.
AB  - NG-nitro-L-arginine methyl ester (L-NAME; 250 micrograms/5 microliters), an
      inhibitor of NO synthase, or the vehicle artificial cerebrospinal fluid (aCSF; 5
      microliters) was administered intracerebroventricularly to conscious rats
      hemorrhaged (0.7 ml/min) to a 20% volume depletion. Hypotension was maximal 5 min
      after hemorrhage ended, with compensatory recovery to basal levels 20 min later,
      regardless of drug treatment. L-NAME, however, elevated (P < 0.05) blood pressure
      (vs. aCSF controls) 40-45 min after intracerebroventricular administration. In
      normovolemic rats, L-NAME produced a significant pressor response and increased
      plasma levels of vasopressin (VP) and oxytocin (OT). After hemorrhage, both
      hormone levels increased, but only OT was further enhanced by L-NAME. Thus
      centrally produced NO tonically inhibits OT and VP secretion under basal
      normovolemic conditions and selectively inhibits OT release during hypovolemia.
      Hemorrhage increased the rates of glucose utilization in the neural lobe,
      indicative of enhanced efferent neural functional activity. L-NAME further
      enhanced the metabolic activity in the entire hypothalamoneurohypophysial system
      of hemorrhaged animals. Several other brain structures involved in the regulation
      of blood pressure and the stress response were also metabolically affected by the
      hemorrhage and L-NAME.

PMID- 9575972
TI  - Phosphorylation of beta-adrenergic receptor leads to its redistribution in rat
      heart during sepsis.
AB  - The role of receptor phosphorylation on the redistribution of beta-adrenergic
      receptors (beta-ARs) in rat hearts during different phases of sepsis was
      investigated. Sepsis was induced by cecal ligation and puncture (CLP). Changes in
      the distribution of beta-ARs in the sarcolemmal and light vesicle fractions were
      studied using (-)-[4,6-propyl-3H]dihydroalprenolol ([3H]DHA). Phosphorylation of
      beta-ARs was studied by perfusing hearts with [32P]H3PO4 followed by
      identification of the phosphorylated beta-ARs with immunoprecipitation using anti
      beta 1-AR antibody. The results show that septic rat hearts exhibit an initial
      hypercardiodynamic (9 h after CLP; early sepsis) and a subsequent
      hypocardiodynamic (18 h after CLP; late sepsis) state. [3H]DHA binding studies
      show that, during early sepsis, the maximum binding capacity (Bmax) was increased
      by 26% in sarcolemma but was decreased by 30% in light vesicles, whereas, during
      late sepsis, the Bmax was decreased by 39% in sarcolemma but increased by 31% in
      light vesicles. These data indicate that beta-ARs in the rat heart were
      externalized from light vesicles to sarcolemma during early sepsis but were
      internalized from surface membranes to intracellular sites during late sepsis.
      The immunoprecipitation studies reveal that the externalization of beta-ARs
      during early sepsis was coupled with a concomitant decrease (-28.5 to -30.6%, P <
      0.01) in the receptor phosphorylation, whereas the internalization of beta-ARs
      during late sepsis was accompanied by a simultaneous increase (30.3 to 33.8%, P <
      0.01) in the receptor phosphorylation. Because the
      phosphorylation/dephosphorylation of beta 1-ARs regulate their functional
      coupling and may reflect their subcellular distribution, it is suggested that the
      increase in receptor phosphorylation seen in late sepsis leads to the receptor
      internalization observed in late sepsis; similarly, externalization of
      (dephosphorylated) receptors in early sepsis may give rise to the apparent
      decrease in sarcolemmal receptor phosphorylation observed during this interval.

PMID- 9575973
TI  - Effects of temperature on sleep in the developing rat.
AB  - In altricial species, such as humans and rats, much of the development of
      autonomic systems occurs postnatally. Consequently, vulnerabilities exist early
      in postnatal development when immature autonomic functions are challenged by
      external factors such as variations in ambient temperature (Ta). Ta profoundly
      influences sleep/wake state structure in adult animals and humans, and exposure
      to excessive warmth has been implicated as a risk factor in sudden infant death
      syndrome. To better understand the relationship between temperature and sleep
      during development, we investigated the effect of Ta variation on sleep/wake
      state structure and sleep intensity in developing rats. In this experiment, sleep
      intensity was measured by the intensity of slow-wave activity during slow-wave
      sleep. Neonatal Long-Evans hooded rat pups were surgically prepared for chronic
      sleep/wake state and brain temperature (Tbr) recording. Two-hour recordings of
      sleep/wake state and Tbr were obtained from rats on postnatal day 12 (P12), P14,
      P16, P18, and P20 at a Ta of either 28.0-30.0, 33.0-35.0, or 38.0-40.0 degrees C.
      Ta significantly influenced sleep/wake state structure but had little, if any,
      effect on sleep intensity in developing rats.

PMID- 9575974
TI  - Insulin-induced repartitioning of metabolic fuels inhibits hamster estrous
      behavior: role of area postrema.
AB  - Excessive diversion of metabolic fuels away from oxidation and into adipose
      tissue storage depots, such as underfeeding or extraordinary levels of energy
      expenditure, can induce nutritional infertility. Treatment with pharmacological
      doses of insulin reduces metabolic fuel availability and suppresses both
      ovulatory cyclicity and pulsatile luteinizing hormone release in females of
      several mammalian species, but little attention has been paid to the effects of
      insulin treatments on reproductive behaviors. Ovariectomized Syrian hamsters were
      injected with long-acting insulin every 12 h for 72 h and were prevented from
      overeating by limiting their intake to approximately 110% of pretreatment levels.
      When given estradiol and progesterone, insulin-treated hamsters exhibited
      significantly reduced levels of sexual receptivity compared with saline-treated
      controls. This insulin-induced inhibition of estrous behavior was prevented by
      lesions of the area postrema. Insulin treatments also caused changes in the
      number of detectable estrogen receptor immunoreactive cells in the hypothalamus
      and preoptic area. Therefore, insulin-induced repartitioning of metabolic fuels
      induces changes in estrous behavior and neural estrogen receptors that are
      indistinguishable from those caused by food deprivation, cold exposure, or
      treatment with metabolic inhibitors.

PMID- 9575975
TI  - Whole cell patch-clamp study of putative vasomotor neurons isolated from the
      rostral ventrolateral medulla.
AB  - A distinct subpopulation of neurons in the rostral and ventrolateral part of the
      medulla oblongata (RVL) plays a key role in controlling sympathetic vasomotor
      tone. To characterize these neurons under conditions in which all cell-to-cell
      interactions are eliminated, RVL neurons were acutely dissociated from 13- to 19
      day old rats. Cells projecting to the upper thoracic segments were retrogradely
      labeled with fluorescent beads. Fifty-two percent (17/33) of examined spinally
      projecting neurons were catecholaminergic, as demonstrated by single-cell reverse
      transcription-polymerase chain reaction or immunocytochemistry. No spontaneous
      (capacitive) spikes were revealed in the tight seal cell-attached configuration.
      Whole cell recordings were made from 54 spinally projecting neurons using Cs(+)-
      or K(+)-containing pipettes. No spontaneous firing was observed in current-clamp
      mode with K(+)-based pipettes (membrane potential, -61.5 +/- 2.3 mV). Step
      depolarizations (300- or 400-ms pulses, up to 100 pA) evoked regular firing or
      one to four spikes. Several voltage-gated currents, resembling the transient and
      persistent Na+, delayed rectifier and low- and high-threshold Ca2+, were revealed
      in voltage-clamp mode. These results show that isolated spinally projecting RVL
      neurons display no pacemaker-like activity. Because data from the literature
      indicate that these neurons are capable of generating such activity under
      different experimental conditions, the factors responsible for different behavior
      need to be determined. Dissociated RVL neurons provide a useful new model for
      studying biophysical and other properties of neurons involved in blood pressure
      control.

PMID- 9575976
TI  - Role of the liver in long-term control of drinking behavior, Na+ balance, and
      arterial pressure in Dahl rats.
AB  - The role of postabsorptive mechanisms in long-term control of drinking behavior,
      Na+ balance, and arterial pressure was examined in Dahl salt-sensitive (DS) and
      salt-resistant (DR) rats. NaCl (0.15 M) was infused (0.5 ml/h) into either the
      inferior vena cava (IVC) or the portal vein (PV) for 7 days, and then 1.5 M NaCl
      was infused for 10 days. During 1.5 M infusion, the IVC group retained more Na+
      than the PV group. Furthermore, in DS rats, mean arterial pressure was higher in
      the IVC group than in the PV group. Regardless of the strain and infusion route,
      1.5 M infusion had no effect on volume of daily saline consumption. However, when
      the data for light and dark periods were analyzed separately, dark period saline
      consumption in the PV group was decreased by 1.5 M infusion but was not changed
      in the IVC group. These results indicate that, in Dahl rats, the postabsorptive
      mechanism plays a significant role in controlling long-term saline drinking
      behavior and Na+ balance and has a significant role in controlling arterial
      pressure in DS, but not DR, rats.

PMID- 9575977
TI  - Contribution of alpha 2-adrenoceptors in caudal ventrolateral medulla to
      cardiovascular regulation in rat.
AB  - The inhibitory action of alpha 2-agonists on the cardiovascular neurons has been
      elucidated in the rostral ventrolateral medulla (RVLM) but not in the caudal
      ventrolateral medulla (CVLM). Our study aimed to clarify whether microinjection
      of clonidine into the CVLM elicits any cardiovascular effect and whether
      endogenous alpha 2-adrenoceptor-mediated mechanisms contribute to the tonic
      activity of the CVLM neurons. In male Sprague-Dawley rats (7-9 wk old, 270-320 g)
      anesthetized with urethan, unilateral microinjection of 8 nmol of clonidine into
      the CVLM (n = 10) increased mean arterial pressure (MAP) and renal sympathetic
      nerve activity (RSNA) by 12.1 +/- 1.8 mmHg (mean +/- SE, P < 0.01) and 25.8 +/-
      4.8% (P < 0.01), while heart rate (HR) remained unaltered. Unilateral
      microinjection of 2 nmol of SKF-86466, a selective blocker of the alpha 2
      adrenoceptors, into the CVLM (n = 10) decreased MAP, HR, and RSNA (-11.6 +/- 2.6
      mmHg, -26 +/- 7 beats/min, and -15.3 +/- 1.7%, respectively, P < 0.01 for each).
      Artificial cerebrospinal fluid caused neither a cardiovascular effect nor a
      sympathetic response. Prior injection of SKF-86466 into the ipsilateral CVLM
      attenuated the effects of clonidine. Bilateral microinjection of muscimol into
      the RVLM abolished the effects of both clonidine and SKF-86466 injected into the
      CVLM. The pressor and sympathoexcitatory effects of clonidine injected into the
      CVLM suggest a neuroinhibitory action of the drug on the CVLM neurons. In
      addition, the depressor and sympathoinhibitory effects of SKF-86466 injected into
      the CVLM indicated that activation of alpha 2-adrenoceptors by endogenous ligand
      inhibits CVLM neurons. The effects of clonidine and the alpha 2-adrenoceptor
      antagonist in the CVLM require the integrity of the RVLM.

PMID- 9575978
TI  - Role of K+ channels in adrenal catecholamine secretion in anesthetized dogs.
AB  - We examined the role of K+ channels in the secretion of adrenal catecholamine
      (CA) in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), 1,1
      dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. K+
      channel blockers and the cholinergic agonists were infused and injected,
      respectively, into the adrenal gland. The voltage-dependent K+ channel (KA type)
      blocker mast cell degranulating (MCD) peptide infusion (10-100 ng/min) enhanced
      increases in CA output induced by SNS (1-3 Hz), but it did not affect increases
      in CA output induced by ACh (0.75-3 micrograms), DMPP (0.1-0.4 microgram), or
      muscarine (0.5-2 micrograms). The small-conductance Ca(2+)-activated K+ (SKCa)
      channel blocker scyllatoxin infusion (10-100 ng/min) enhanced the ACh-, DMPP-,
      and muscarine-induced increases in CA output, but it did not affect the SNS
      induced increases in CA output. These results suggest that KA channels may play
      an inhibitory role in the regulation of adrenal CA secretion in response to SNS
      and that SKCa channels may play the same role in the secretion in response to
      exogenously applied cholinergic agonists.

PMID- 9575979
TI  - Temperature-dependent feeding: lack of role for leptin and defect in brown
      adipose tissue-ablated obese mice.
AB  - The objective was to characterize the ability of control and transgenic brown
      adipose tissue (BAT)-ablated uncoupling protein diphtheria toxin A chain (UCP
      DTA) mice to adjust food intake in relation to changes in environmental
      temperature and to assess the involvement of leptin in this adjustment. We
      measured serum leptin in mice from a previous study of UCP-DTA mice raised at
      thermoneutrality (35 degrees C) or at the usual rearing temperature (24 degrees
      C) from weaning [Melnyk, A., M. -E. Harper, and J. Himms-Hagen. Am. J. Physiol,
      272 (Regulatory Integrative Comp. Physiol. 41): R1088-R1093, 1997] and extended
      the study by acclimating control and obese UCP-DTA mice at 18 wk of age to cold
      (14 degrees C) for up to 14 days. Leptin levels did not change in control mice at
      14 degrees C; however, food intake increased threefold within 1 day and remained
      at this level. Serum leptin level was elevated in UCP-DTA mice at 24 degrees C
      compared with control mice at 24 degrees C; this elevated level decreased within
      1 day at 14 degrees C and was not different from the level in control mice by 14
      days. Food intake of UCP-DTA mice that were hyperphagic at 24 degrees C did not
      change during 7 days at 14 degrees C, then increased slowly. Similar low leptin
      levels were present in control mice raised at 24 or 35 degrees C and in UCP-DTA
      mice raised at 35 degrees C. Food intake of control mice raised at 24 degrees C
      was two times that of control mice raised at 35 degrees C. UCP-DTA mice raised at
      35 degrees C ate the same low amount as control mice raised at 35 degrees C. UCP
      DTA mice at 24 degrees C were hyperphagic relative to control mice at 24 degrees
      C yet had elevated leptin levels in their serum. Two principal conclusions are
      drawn. First, adjustment of food intake over a fourfold range by control mice
      acclimated to temperatures from 35 down to 14 degrees C is independent of changes
      in serum leptin levels. Second, this adjustment of food intake in relation to
      temperature is defective in the UCP-DTA mouse; the defect leads to hyperphagia at
      24 degrees C and a failure to increase food intake as rapidly as control mice
      when exposed to 14 degrees C. Because lack of UCP-1-mediated thermogenesis in BAT
      of knockout mice is known not to induce hyperphagia, we propose that deficiency
      of UCP-1-expressing brown adipocytes in BAT of UCP-DTA mice results in lack of a
      satiety factor, secreted by these cells in BAT of control mice in inverse
      relationship to sympathetic nervous system activity.

PMID- 9575980
TI  - Primary vagally mediated decelerations in heart rate during tonic rapid eye
      movement sleep in cats.
AB  - Rapid eye movement (REM) sleep results in profound state-dependent alterations in
      heart rate. The present study describes a novel phenomenon of a primary
      deceleration in heart rate that is not preceded or followed by increases in heart
      rate or arterial blood pressure and occurs primarily during tonic REM sleep. The
      goals were to characterize the primary decelerations and to provide insights on
      the underlying central and peripheral autonomic mechanisms. Cats were chronically
      implanted with electrodes to record electroencephalogram, pontogeniculooccipital
      wave activity in lateral geniculate nucleus, hippocampal theta rhythm,
      electromyogram, electrooculogram, respiration (diaphragm), and electrocardiogram.
      Arterial blood pressure was monitored from a carotid artery catheter. R-R
      interval fluctuations were continuously tracked using customized software. The
      muscarinic blocking agent glycopyrrolate (0.1 mg/kg i.v.) and the beta-adrenergic
      blocking agent atenolol (0.3 mg/kg i.v.) were administered in alternating
      sequence with a 90- to 120-min interval. Glycopyrrolate immediately eliminated
      the decelerations during REM sleep. Atenolol alone had no effect on their
      frequency. These findings suggest that a change in the centrally induced pattern
      of autonomic activity to the heart is responsible for the primary decelerations,
      namely, a bursting of cardiac vagal efferent fiber activity.

PMID- 9575981
TI  - Central nitric oxide attenuates the baroreceptor reflex in conscious rabbits.
AB  - We examined the role of central nitric oxide (NO) in the baroreceptor reflex in
      conscious rabbits. Intracerebroventricular infusion of 20 mumol of N omega-nitro
      L-arginine methyl ester (L-NAME) to block central NO resulted in increases in
      arterial pressure, renal sympathetic nerve activity (RSNA), and plasma
      catecholamine levels, and the pressor response was suppressed by pretreatment
      with pentolinium (5 mg/kg i.v.). On the other hand, a subpressor dose of
      intracerebroventricular L-NAME (10 mumol/h) caused significant increases in
      baroreflex sensitivities assessed by RSNA and heart rate compared with vehicle
      infusion [maximum gain: -18.2 +/- 0.9 vs. -9.6 +/- 0.9%/mmHg (P < 0.001) and 
      14.3 +/- 2.3 vs. -5.7 +/- 0.4 beats.min-1.mmHg-1 (P < 0.05), respectively].
      Conversely, an intracerebroventricular infusion of Et2N[N(O)NO]Na, an NO donor (1
      mumol/h) significantly attenuated the baroreflex sensitivities. However,
      intracerebroventricular infusion of N omega-nitro-D-arginine methyl ester (10
      mumol/h), an enantiomer of L-NAME, failed to alter the baroreflex sensitivities.
      These results suggest that 1) the pressor response induced by inhibition of
      central NO synthesis is mainly mediated by the enhanced sympathetic outflow and
      2) central NO attenuates the baroreflex control of RSNA and heart rate in
      conscious rabbits.

PMID- 9575982
TI  - Renal neutral alpha-D-glucosidase has no role in transport of D-glucose derived
      from maltose hydrolysis.
AB  - To reinvestigate the "hydrolase-related transport" concept, neutral alpha-D
      glucosidase, a membrane-bound disaccharidase of renal proximal tubule, was first
      purified from brush-border membranes and then asymmetrically reincorporated into
      egg phosphatidylcholine vesicles. Proteolytic treatments and immunotitration
      studies demonstrated that this enzyme was integrated in native and artificial
      membrane vesicles with a similar topology. The uptake of free glucose and glucose
      produced by maltose hydrolysis was studied using 1) proteoliposomes containing
      integrated neutral alpha-D-glucosidase, in combination with other membrane
      proteins, and 2) proteoliposomes containing only the other membrane proteins but
      incubated in a medium containing neutral alpha-D-glucosidase in its hydrophilic
      form. No modification was observed in the uptake of free D-glucose or D-glucose
      produced by maltose hydrolysis, regardless of enzyme localization. In contrast to
      previous findings on the hydrolase-related transport concept, these results rule
      out any participation of neutral alpha-D-glucosidase in the transport of free
      glucose or glucose produced by maltose hydrolysis. Hydrolytic activity and
      transmembrane transport appear to be two independent and sequential steps.

PMID- 9575983
TI  - Cerebral cortex does not modulate "regulated" decrease in core temperature during
      hypoxemia in rats.
AB  - In newborns and adults of a number of species including humans, exposure to acute
      hypoxemia produces a "regulated" decrease in core temperature, the mechanism of
      which is unknown. Considering that various cortical areas participate in
      autonomic regulation including thermoregulation, the present experiments were
      carried out to test the hypothesis that the cerebral cortex plays a role in
      modulating the regulated decrease in core temperature during acute hypoxemia.
      This hypothesis was tested by determining the core temperature response to acute
      hypoxemia in chronically instrumented adult Sprague-Dawley rats before and after
      cortical spreading depression (i.e., functional decortication) was produced by
      the local application of potassium chloride to the dura overlying the cerebral
      hemispheres. There was no effect of cortical spreading depression on baseline
      core temperature. Core temperature decreased during acute hypoxemia in a similar
      fashion when the cerebral cortex was intact as well as during functional
      decortication. Thus our data do not support the hypothesis that the cerebral
      cortex modulates the regulated decrease in core temperature that occurs in adult
      rats during acute hypoxemia.

PMID- 9575984
TI  - Experimental separation of time of day and homeostatic influences on sleep.
AB  - The purpose of the present study was to evaluate the simultaneous effects on
      sleep of prior time awake (PRW) and time of day (TOD). Eight male subjects spent
      13 days in an isolated sleep lab and had three 8-h baseline sleeps and then 18 4
      h sleeps, distributed to provide three sleeps starting at 2400, 0400, 0800, 1200,
      1600, and 2000. The three sleeps were preceded by 4, 8, and 12 h of PRW,
      respectively. ANOVA showed that TST and subjective sleepiness increased with PRW
      and with closeness to the trough of the circadian rhythm of rectal temperature,
      whereas sleep latency showed the opposite pattern, and rapid eye movement sleep
      (REM) latency strongly decreased with PRW and with closeness to the trough. Slow
      wave sleep (SWS) increased with PRW, whereas SWS latency and final time awake
      decreased. REM sleep increased with closeness to the circadian trough, and time
      awake decreased. Multiple-regression analysis showed that REM latency was closely
      related to increased SWS in the first sleep cycle, reduced SWS latency, and
      increased PRW [a short PRW before sleep at noon yielded an extremely short (14
      min) REM latency]. Sleep latency and final time awake showed almost exactly the
      same relationship to TOD and PRW. It is concluded that both homeostatic and
      circadian influences simultaneously affect sleep, that REM latency is very
      sensitive to the need for SWS, and that the circadian acrophase strongly
      interferes with sleep. It should be emphasized that the conclusions should not be
      extrapolated to longer (> 12 h) wake spans.

PMID- 9575985
TI  - Direct fetal glucocorticoid treatment alters postnatal adaptation in premature
      newborn baboons.
AB  - Abnormalities of premature newborn adaptation after preterm birth result in
      significant perinatal mortality and morbidity. We assessed the effects of short
      term (24 h) fetal betamethasone exposure on preterm newborn baboon pulmonary and
      cardiovascular regulation and renal sodium handling during the first 24 h after
      birth. Male fetal baboons (Papio) (124-day gestation, term 185 days) received
      ultrasound-guided intramuscular injections of saline (n = 5) or betamethasone
      (0.5 mg/kg; n = 5). Fetuses were cesarean delivered 24 h later, treated with 100
      mg/kg surfactant, and ventilated by adjusting peak inspiratory pressures to
      maintain PCO2 values of 35-50 mmHg for 24 h. Betamethasone- vs. saline-treated
      mean +/- SE newborn body weights (0.45 +/- 0.02 vs. 0.41 +/- 0.01 kg) were
      similar. Although prenatal betamethasone did not affect postnatal lung function
      (PCO2, arterial/alveolar O2 gradient, or dynamic compliance), plasma hormone
      (cortisol or thyroxine), or catecholamine levels, mean arterial pressure (25 +/-
      1 vs. 32 +/- 1 mmHg), plasma sodium concentration (132 +/- 2 vs. 138 +/- 1
      meq/l), glomerular filtration rate (0.07 +/- 0.02 vs. 0.16 +/- 0.02 ml.min-1.kg
      1), and renal total sodium reabsorption (1.5 +/- 0.5 vs. 16.0 +/- 3.0 mu eq.min
      1.kg-1) values were significantly lower in saline-treated than in betamethasone
      treated newborns at 24 h. We conclude that despite the fact that there are no
      pulmonary and endocrine effects, antenatal glucocorticoid exposure alters
      premature newborn baboon vascular and renal glomerular function and improves
      sodium reabsorption after preterm delivery.

PMID- 9575986
TI  - Stanniocalcin in the seawater salmon: structure, function, and regulation.
AB  - Stanniocalcin (STC) is a homodimeric glycoprotein hormone that was first
      discovered in fish, where it is produced by unique endocrine glands known as the
      corpuscles of Stannius (CS). In freshwater salmon, STC plays an integral role in
      Ca2+ and phosphate homeostasis. High levels of extracellular Ca2+ promote the
      synthesis and release of STC, which on entering the bloodstream reduces the
      levels of gill and gut Ca2+ transport and renal phosphate excretion to restore
      normocalcemia. In this report, we have examined STC in seawater salmon. We have
      studied the distribution of STC protein and mRNA in marine Atlantic salmon CS
      cells, the responsiveness of these cells to Ca2+, and some physical properties of
      the hormone. Our results demonstrated that all Atlantic salmon CS cells expressed
      the STC gene. Furthermore, these cells exhibited a Ca2+ sensitivity that was
      remarkably similar to those in freshwater salmon in terms of its ability to
      stimulate STC secretion and gene expression. When Atlantic salmon glands were
      fractionated by concanavalin A (ConA)-Sepharose chromatography, two distinct
      forms of the hormone were identified, both of which were recognized by sockeye
      salmon STC antiserum, and designated as STC1 and STC2. STC1 was a glycosylated,
      42-kDa disulfide-linked dimer, with a high affinity for ConA. STC2 did not bind
      to ConA, was 44 kDa in size, and had a different subunit structure. STC2 was also
      a less effective inhibitor of gill Ca2+ transport in fish. Collectively, the
      results suggest that there is a second form of STC in salmon.

PMID- 9575987
TI  - Selective REM sleep deprivation in humans: effects on sleep and sleep EEG.
AB  - To investigate rapid eye movement (REM) sleep regulation, eight healthy young men
      were deprived of REM sleep for three consecutive nights. In a three-night control
      sleep deprivation (CD) session 2 wk later, the subjects were repeatedly awakened
      from non-REM sleep in an attempt to match the awakenings during the REM sleep
      deprivation (RD) nights. During the RD nights the number of sleep interruptions
      required to prevent REM sleep increased within and across consecutive nights. REM
      sleep was reduced to 9.2% of baseline (CD nights: 80.7%) and rose to 140.1% in
      the first recovery night. RD gave rise to changes in the EEG power spectra of REM
      sleep. Power in the 8.25- to 11-Hz range was reduced in the first recovery night,
      an effect that gradually subsided but was still present in the third recovery
      night. The rising REM sleep propensity, as reflected by the increase of
      interventions within and across RD nights, and the moderate REM sleep rebound
      during recovery can be accounted for by a compensatory response that serves REM
      sleep homeostasis. The changes in the electroencephalogram power spectra, which
      were observed during enhanced REM sleep propensity, may be a sign of an altered
      quality of REM sleep.

PMID- 9575989
TI  - Between a rock and a hard place. The plight of surgeons advocating progress
      through new technology.

PMID- 9575988
TI  - Catecholaminergic regulation of venous function in the rainbow trout.
AB  - The significance of the sympathetic nervous system (SNS) in regulating peripheral
      vascular resistance and cardiac function in fish has been well established,
      whereas its effect on venous function in vivo is unknown. Two protocols were
      employed in the present study to evaluate SNS effects on the venous system in
      intact, unanesthetized trout. In the first, trout were instrumented with pressure
      cannulas in the ventral (PVA) and dorsal (PDA) aortas and ductus Cuvier (PVEN),
      and cardiac output (CO) was measured with a flow probe around the ventral aorta.
      Heart rate, stroke volume, and gill and systemic resistances were calculated from
      the measured parameters. In the second group, vascular capacitance curves were
      obtained by monitoring mean circulatory filling pressure (PVEN) during transient
      interruption of CO and while blood volume was adjusted between 80 and 120% of
      normal. Unstressed blood volume (USBV) and vascular compliance (C) were derived
      from the capacitance curves. Infusion of epinephrine (Epi; 3.3 nmol.min-1.kg body
      wt-1) increased PVA, PDA, and PVEN, whereas norepinephrine (NE) infusion (3.3
      nmol.min-1.kg body wt-1) increased PVA and PDA but did not affect PVEN. Epi (1.0
      nmol.min-1.kg body wt-1), but not NE (2.6 or 10.4 nmol.min-1.kg body wt-1),
      displaced the capacitance curve to the right and significantly decreased USBV.
      Inhibition of alpha 1-adrenoceptors with prazosin, or ganglionic nicotinic
      receptor blockade with hexamethonium, produced a left shift in the capacitance
      curve, and both treatments increased USBV and C. Conversely, the alpha
      adrenoceptor antagonist phentolamine did not effect vascular capacitance. These
      results show that Epi has potent effects on trout veins in vivo and that it
      mobilizes blood from the unstressed into the stressed vascular compartment and
      augments central venous pressure by decreasing venous compliance. These results
      also show that the SNS is an active effector of venous tone and compliance in
      trout; this is the first demonstration of tonic regulation of vascular
      capacitance in any fish.

PMID- 9575990
TI  - Surgical images. Aortoduodenal fistula.

PMID- 9575991
TI  - Radiology for the surgeon. Case 20. Obstruction secondary to extrinsic
      compression of the rectosigmoid junction against the sacrum by a distended
      bladder.

PMID- 9575992
TI  - Host response to laparoscopic surgery: mechanisms and clinical correlates.
AB  - Minimal access surgery has revolutionized the treatment of a variety of surgical
      diseases, partly because it is associated with less patient morbidity than
      nonlaparoscopic surgical procedures. Emerging evidence suggests that alteration
      in the host response after laparoscopic procedures has significantly contributed
      to the improved postoperative course. Laparoscopy modulates both afferent stimuli
      (including tissue trauma, pain and wound size) and efferent responses (via
      neuroendocrine, metabolic, immunologic and cardiorespiratory systems). These
      effects lead to a decrease in postoperative pain, fever and disability.
      Laparoscopy mediates these effects through reduced wound size, the activities of
      endotoxin and immunomodulatory actions of the insufflated gas, resulting in
      impaired macrophage activity. Although clearly beneficial in reducing
      postoperative morbidity after elective surgery, this immunosuppression could
      increase the risk of complications during procedures for infection or neoplasia.

PMID- 9575993
TI  - An analysis of open reduction of irreducible supracondylar fractures of the
      humerus in children.
AB  - OBJECTIVES: To review experience with irreducible supracondylar fractures
      requiring open reduction in children, and to propose guidelines for an open
      approach to supracondylar fractures. DESIGN: A chart review. SETTING: The
      Children's Hospital of Eastern Ontario (CHEO), a pediatric centre with a large
      referral base. PATIENTS: Forty-one children (18 boys 23 girls, average age 7
      years), who had open reduction of irreducible supracondylar fractures at the CHEO
      over a 10-year period (1985 to 1995). Of these 41 children, 7 were lost to direct
      follow-up. INTERVENTIONS: After closed reduction of displaced supracondylar
      fractures of the humerus failed, all patients underwent open reduction and
      percutaneous fixation in the operating room. Before operation, 6 had no radial
      pulse, 5 lost their pulse with flexion after reduction and 4 had unstable
      fracture patterns. MAIN OUTCOME MEASURES: Assessment of elbow range of motion and
      carrying angle, distal neurovascular status and radiographic measurement of the
      Baumann angle and the humerocapitellar angle. RESULTS: In 25 children, the
      humerus was found to have "buttonholed" through the brachialis muscle; 1 had
      entrapment of the common flexor muscle at its origin and 1 had entrapment of the
      triceps. In 15 children there was entrapment or tethering of the median nerve and
      radial nerve or brachial artery, or both, but this was not predictive of
      preoperative neurovascular deficit, which was recorded in 21 patients (fully
      recovered). At follow-up, the Baumann angle and the humerocapitellar angle
      differed by an average of 2 degrees and 5.3 degrees respectively compared with
      the unaffected arm. Range of motion was satisfactory in 94% of patients, and
      there was no significant cubitus varus. CONCLUSION: Open reduction of
      supracondylar fractures is a safe and effective procedure, for which orthopedists
      should should lower their threshold, given certain appropriate indicators.

PMID- 9575994
TI  - The carpal stretch test.
AB  - OBJECTIVE: To compare the sensitivity of traditional motion studies, bone
      scintigraphy and radiocarpal arthrography to a "carpal stretch test," for
      evaluation of dynamic dissociative carpal instability. DESIGN: Experimental study
      comparing the results of the tests to the findings of arthroscopy, the "gold
      standard." SETTING: A university hospital-based upper extremity practice.
      PATIENTS: Six patients with chronic wrist pain, arthroscopically confirmed
      proximal row ligamentous disruption and radiographs not suggestive of proximal
      row instability. INTERVENTIONS: The carpal stretch test: both affected and
      unaffected wrists were subjected to the same testing, wherein the wrist was
      suspended from finger traps for 10 minutes by a 4.5-kg weight. Standardized
      posteroanterior radiographs were taken of the suspended wrists. MAIN OUTCOME
      MEASURES: Disruption of Gilula's arcs I and II, and sensitivity of the carpal
      stretch test compared with other investigations. MAIN RESULTS: Step deformities
      ranging from 2.5 to 6 mm (average 3.7 mm) were recorded in the affected wrists
      and 0 to 4 mm (average 1.5 mm) in the "unaffected" wrists. The test was more
      sensitive than traditional radiography, arthrography and scintigraphy in defining
      both presence and site of proximal carpal row ligamentous tears and was almost as
      sensitive as arthroscopy. CONCLUSION: In patients with chronic wrist pain and
      dynamic dissociative wrist instability, the carpal stretch test may prove to be a
      valuable screening tool for detecting ligamentous tears of the proximal carpal
      row.

PMID- 9575995
TI  - The role of diagnostic block in the management of Morton's neuroma.
AB  - OBJECTIVE: To determine the outcome of surgical excision of Morton's neuroma
      after a local anesthetic diagnostic block into the neuroma has relieved symptoms.
      DESIGN: A cohort study. SETTING: A university affiliated hospital. PATIENTS: A
      sequential series of 37 patients who underwent 41 excisions with at least 2
      years' follow-up. Seven patients had undergone repeat excision of a neuroma, and
      34 primary excisions were performed. Surgery was performed by a specialist in
      orthopedic surgery of the foot and ankle. INTERVENTION: Excision of the Morton's
      neuroma after a positive diagnostic block. MAIN OUTCOME MEASURES: Grade of
      symptoms at follow-up done by independent review on a 4-point scale. RESULTS: Of
      41 procedures, 11 had an unfavourable outcome: 4 procedures were graded 3, and 7
      procedures were graded 4. Eight (24%) of the 34 primary procedures were reported
      as failures, and 3 (43%) of the 7 revision procedures were reported as failures.
      Most patients reported poor results owing to persistent pain. CONCLUSIONS:
      Diagnostic blocks do not improve the results of surgery for excision of Morton's
      neuroma and are not recommended. Because failure rates are greater than 20%,
      surgery for Morton's neuroma should only be offered after a full course of
      nonoperative management.

PMID- 9575996
TI  - Surgical treatment of hydatid cysts of the lung: analysis of 405 patients.
AB  - OBJECTIVE: The choice of operation, postoperative success and complications of
      surgery in patients with pulmonary hydatid cysts. DESIGN: A series of patients
      seen over 15 years. SETTING: A university clinic. PATIENTS: Four hundred and five
      patients (209 male, 196 female) ranging in age from 4 to 72 years (mean 29
      years). Most (367 patients) had isolated lung cysts; 38 had both liver and lung
      cysts. INTERVENTIONS: A variety of procedures to remove cysts, including
      enucleation and capitonnage, wedge resection, segmentectomy, lobectomy and
      pneumonectomy. Six patients with bilateral cysts were operated on through a
      median sternotomy approach. Others underwent posterolateral thoracotomy. MAIN
      OUTCOME MEASURES: Value of diagnostic tests, the most efficacious approach for
      cyst removal and recurrence and death rates. RESULTS: Chest radiography gave a
      correct diagnosis in 99% of patients. The Casoni and Weinberg tests were
      discontinued because of high false-negative rates (up to 35%). Hospital mortality
      was 1.2% and postoperative complications occurred in 5.2%. The recurrence rate
      was 1.5%. CONCLUSIONS: Lung-preserving surgical interventions are the treatment
      of choice for pulmonary hydatid disease. In patients with bilateral cysts, the
      median sternotomy approach is preferred, and in the patients with right lung
      disease and coexisting liver cysts the transdiaphragmatic approach is the one of
      choice to remove cysts in 1 stage.

PMID- 9575997
TI  - A prospective comparison of the costs of reusable and limited-reuse laparoscopic
      instruments.
AB  - OBJECTIVE: To compare the cost and performance of 2 types of laparoscopic
      instrumentation: reusable laparoscopic hook cautery instruments and curved
      scissors, or limited-reuse laparoscopic hook cautery instruments and curved
      scissors. DESIGN: A randomized trial. SETTING: The operating room of a tertiary
      care hospital. METHOD: All general surgeons performing laparoscopic procedures at
      the hospital were randomized to be supplied with either reusable or limited-reuse
      hook cautery and curved scissors. Instrument use was recorded, together with
      principal outcome measures. OUTCOME MEASURES: Life expectancy of the instruments,
      the number of cases for which they were used, the number, nature and cost of
      repairs, their purchase cost and surgeon satisfaction. RESULTS: Reusable hook
      cautery instruments were less expensive than their limited-reuse counterparts.
      Excellent surgeon satisfaction was reported with the use of this type of
      instrument. The limited-reuse curved scissors arm of the study was terminated
      early because of a breach in study protocol. CONCLUSIONS: Reusable hook cautery
      instruments were better than their limited-reuse counterparts. Rigorous attempts
      to compare the cost of laparoscopic instruments may be limited by their rapid
      evolution in design and the availability of many types of instruments on the
      market.

PMID- 9575998
TI  - Metabolic monitoring during continuous warm- and cold-blood cardioplegia by means
      of myocardial tissue pH and PO2.
AB  - OBJECTIVES: To study the changes in myocardial tissue pH and PO2 during cold- and
      warm-blood cardioplegic arrests. DESIGN: An experimental study in dogs. METHODS:
      Nine dogs underwent the following procedures: 30 minutes with an empty heart
      beating under cardiopulmonary bypass (control period); 30 minutes of warm (33
      degrees C) cardioplegic arrest with a 1:4 mix of crystalloid in blood solution
      administered continuously at 150 mL/min; 30 minutes of cold (15 degrees C)
      cardioplegic arrest; and 30 minutes of myocardial reperfusion. The cardioplegic
      blood solution was administered antegradely through the ascending aorta. MAIN
      OUTCOME MEASURES: Tissue pH and PO2. Arterial and coronary sinus oxygen content
      and myocardial consumption calculated. RESULTS: There was a modest but
      significant increase in the left anterior descending (LAD) and circumflex (Cx)
      tissue pH throughout the experiment. PmO2 in the LAD territory averaged 44 (7) mm
      Hg (mean and standard error of the mean) during the bypass period, 123 (23) mm Hg
      at the termination of warm cardioplegic arrest, 146 (28) mm Hg at the end of cold
      arrest and 66 (17) mm Hg after reperfusion. Oxygen consumption averaged 0.65
      (0.15) mL/min during the bypass period, 0.3 (0.18) mL/min at the end of warm
      arrest, 0.25 (0.16) mL/min at the end of cold arrest and 0.45 (0.08) mL/min after
      reperfusion (p < 0.05). Oxygen delivery to the LAD territory was greater than
      myocardial oxygen consumption by an average of 2.02 (0.4) mL/min during bypass,
      2.02 (0.62) mL/min after warm arrest, 2.12 (0.5) mL/min after cold arrest and
      1.55 (0.25) mL/min after reperfusion (p > 0.05). CONCLUSIONS: During cardioplegic
      arrest, tissue PO2 increased and oxygen consumption decreased significantly,
      whereas tissue pH remained normal, suggesting that continuous warm- and cold
      blood cardioplegia maintained aerobic glycolysis during myocardial arrest. Thus,
      the increase in myocardial tissue PmO2 during cardioplegic arrest reflects the
      decrease in myocardial oxygen consumption while maintaining oxygen supply.

PMID- 9575999
TI  - Balloon pyloroplasty in children with delayed gastric emptying.
AB  - OBJECTIVE: To evaluate initial experience with balloon pyloroplasty for delayed
      gastric emptying in children. DESIGN: A retrospective review. SETTING: A tertiary
      care pediatric hospital. PATIENTS: Seven children with scintiscan-proven delayed
      gastric emptying that was refractory to maximal medical therapy. INTERVENTIONS:
      Balloon pyloroplasty under fluoroscopic guidance, mostly on an outpatient basis.
      For 1 child, the procedure was endoscopically monitored also. OUTCOME MEASURES:
      Postoperative symptoms and physical findings, gastric emptying and complications.
      RESULTS: Of the 7 children who underwent balloon pyloroplasty, 3 were rendered
      asymptomatic and 2 more were symptomatically improved. Four of the original 7
      patients underwent postdilation scintigraphy, and all 4 showed normalization of
      the gastric emptying time. There were no complications. CONCLUSIONS: Initial
      experience with fluoroscopically-guided balloon pyloroplasty indicates that it is
      a safe and easily tolerated procedure, worthy of further study.

PMID- 9576000
TI  - Necrotizing fasciitis of the retroperitoneum: an unusual presentation of group A
      Streptococcus infection.
AB  - A 14-year-old girl presented with symptoms resembling acute appendicitis. Five
      days after appendectomy and continued fever and severe abdominal pain, blood
      cultures were found positive for Streptococcus pyogenes. Two days later a
      diagnosis of group A streptococcal peritonitis with necrotizing retroperitoneal
      fasciitis was confirmed by retroperitoneal cultures obtained at laparotomy.
      Although multiple organ systems showed impaired functioning, including hepatic,
      renal and respiratory changes, she did not meet the criteria for streptococcal
      toxic shock syndrome. She was treated with a combination of high-dose parenteral
      penicillin and clindamycin, followed by prolonged treatment with clindamycin
      orally. Recovery was complicated by persistent hydronephrosis, which was slow to
      resolve.

PMID- 9576001
TI  - Laparoscopic resection of an intra-abdominal cystic mass: a cystic mesothelioma.
AB  - The clinical features of a patient with an intra-abdominal cystic mass do not
      lead to a specific diagnosis. Aspiration is usually ineffective because the mass
      recurs and cytologic investigation is often non-diagnostic. Conservative
      management is unsuccessful because symptoms often persist. Surgical management of
      cystic masses is required for definitive management and pathologic diagnosis. A
      laparoscopic approach to the diagnosis and treatment can provide essential
      anatomic information and a complete resection with minimal morbidity. A
      laparoscopic technique using 3 trocars and maintaining the integrity of the mass
      allows complete excision and removal of large intra-abdominal cystic masses as
      reported in a 43-year-old patient with a large intra-abdominal cystic mass
      identified as a benign cystic mesothelioma.

PMID- 9576002
TI  - The utility of the surgical clerkship elective.

PMID- 9576003
TI  - Ethical allocation of surgical resources.

PMID- 9576004
TI  - Role of Fas/FasL interaction in physiology and pathology: the good and the bad.

PMID- 9576006
TI  - Nasal tolerance to experimental autoimmune myasthenia gravis: tolerance reversal
      by nasal administration of minute amounts of interferon-gamma.
AB  - Tolerance to B cell-mediated experimental autoimmune myasthenia gravis (EAMG), an
      animal model for myasthenia gravis (MG) in humans, can be achieved by nasal
      administration of the autoantigen acetylcholine receptor (AChR). Nasal tolerance
      induction requires only 1/1000 of the amount of AChR used for oral tolerance
      induction, but is as effective in preventing EAMG. To investigate whether nasally
      induced tolerance to EAMG can be influenced by nasal administration of cytokines,
      recombinant rat IFN-gamma (total 5000 U/rat), a combination of AChR and IFN-gamma
      or AChR alone was given nasally to Lewis rats before immunization with AChR and
      complete Freund's adjuvant (CFA). One additional group of rats received the same
      amount of AChR nasally in conjunction with IFN-gamma (total 5000 U/rat)
      intraperitoneally. AChR given alone nasally induced effective tolerance to EAMG
      whereas rats receiving AChR + IFN-gamma by the nasal route exhibited a similar
      disease pattern, and similarly escalated T and B cell responses to AChR when
      compared to control EAMG rats. In contrast, administration of IFN-gamma i.p.
      together with AChR nasally did not affect the induction of tolerance to EAMG. IFN
      gamma given alone nasally did not affect clinical EAMG. This study demonstrates
      that nasal tolerance can be modulated by nasal administration of minute amounts
      of IFN-gamma. Nasal administration of certain cytokines with beneficial effects
      might broaden the effectiveness of applying nasal tolerance as a potential
      therapeutic means of preventing autoimmune diseases.

PMID- 9576005
TI  - CD1--a new paradigm for antigen presentation and T cell activation.
AB  - Despite identification of the CD1 family of molecules in the late 1970s, the
      function of CD1 was undetermined for more than a decade. Recent evidence has
      established that CD1 molecules comprise a novel lineage of antigen-presenting
      molecules, distinct from major histocompatibility complex (MHC) class I and class
      II molecules. Unlike the MHC molecules, which bind short peptides in their
      antigen-binding groove for presentation to either CD4+ or CD8+ T cells bearing
      alpha beta T cell receptors, the CD1 molecules appear to accommodate lipid and
      glycolipid antigens in their hydrophobic cavity for presentation to a wide
      variety of T cells, including double-negative alpha beta and gamma delta T cells
      and CD8+ alpha beta T cells. By using a unique cytoplasmic signal, some CD1
      molecules traffic to endosomal compartments for sampling mycobacteria-derived
      lipid antigens, and subsequently lipid antigen-loaded CD1 molecules are expressed
      on the cell surface to activate specific T cells. These CD1-restricted T cells
      kill mycobacteria-infected cells and secrete interferon-gamma, indicating a
      potential role of CD1-mediated T cell responses in clearing mycobacterial
      infection. The identification of an MHC-independent antigen presentation pathway
      for nonpeptide antigens provides new insights into immunoregulation and host
      defense.

PMID- 9576007
TI  - Enhanced lymphoproliferation and diminished autoimmunity in CD4-deficient MRL/lpr
      mice.
AB  - MRL/lpr mice spontaneously develop an autoimmune disease with features of
      systemic lupus erythematosus. They also develop a lymphoproliferative disorder
      characterized by a massive accumulation of double-negative (DN) T cells that lack
      both CD4 and CD8. To clarify the role of CD4 in autoimmunity and
      lymphoproliferation in these mice, CD4-deficient MRL/lpr mice were generated. CD4
      deficient MRL/lpr mice developed massive expansion of DN T cells in the blood,
      spleen, and lymph nodes, which significantly exceeded the degree of
      lymphoproliferation in CD4-expressing control MRL/lpr mice. Despite this
      lymphoproliferation, CD4-deficient MRL/lpr mice produced little, if any,
      antibodies to double-stranded DNA, and they had prolonged survival relative to
      CD4-expressing littermates. However, they eventually developed moderately severe
      nephritis, characterized by immunoglobulin and complement deposition in
      glomeruli, vasculitis, and renal infiltration by CD8+ T cells. These findings
      indicate that (1) lymphoproliferation in MRL/lpr mice does not require the
      expression of CD4; (2) autoantibody production in MRL/lpr mice is dependent on
      the expression of CD4 and not on the accumulation of DN T cells; and (3) the
      development of nephritis in MRL/lpr mice involves both CD4-dependent and CD4
      independent mechanisms.

PMID- 9576009
TI  - Selective response of CD5+ B cell malignancies to activation of the CD72 antigen.
AB  - The function of the simultaneous expression of CD5 and its ligand CD72 on B cell
      malignancies like chronic lymphocytic leukemia and mantle cell lymphoma was
      assessed. It is unknown if reciprocal interactions between CD72 and CD5 exert an
      autocrine growth-promoting or -inhibiting effect. CD5+ (n = 13) and CD5- (n = 9)
      B cell malignancies were cultured with the anti-CD72 mAb WL225. For comparison,
      five other anti-CD72 mAbs were tested. Only CD5+ B cell malignancies proliferated
      upon CD72 activation (9 out of 13 cases). A strong suppressive effect of IL-4 on
      the anti-CD72-induced [3H]thymidine incorporation, partially caused by
      downmodulation of the CD72 expression, was seen. Stimulation of the CD5 antigen
      by L cells transfected with human CD72 (LhCD72) and the anti-CD5 mAb 1C12 exerted
      no (n = 9) or a minor effect (2 out of 8 cases), respectively. Finally, the
      results of CD72 stimulation were compared with CD40 stimulation, as this "CD40
      system" is an effective method for stimulating B cell malignancies. In 4 of the 7
      anti-CD72 responsive cases a costimulatory effect was seen.

PMID- 9576008
TI  - CD95 expression and apoptosis during pediatric HIV infection: early upregulation
      of CD95 expression.
AB  - Pediatric HIV infection is characterized by a progressive decline in CD4 T
      lymphocytes and faster disease progression than is typically seen in adults.
      Apoptosis, possibly mediated through the CD95 antigen, has been proposed as a
      mechanism for cell loss which eventually leads to immune dysfunction. In this
      study of peripheral blood lymphocytes from HIV-infected children, classified
      according to CDC immunologic categories, we found that the percentage of CD4 and
      CD8 T cells expressing CD95 and the percentage of lymphocytes undergoing
      apoptosis were increased in children with HIV infection and were greater in
      children from immunologic Category III as compared to those in Category I. Most
      striking was our observation that an increased percentage of CD95-positive cells
      appeared as early as 3 months of age, at a time when these children did not have
      elevated levels of apoptosis. These data demonstrate early upregulation of CD95
      expression in HIV-infected infants, an abberation which may have profound
      implications for the pathogenesis of perinatally acquired HIV disease.

PMID- 9576010
TI  - Detection of a soluble form of B7-1 (CD80) in synovial fluid from patients with
      arthritis using monoclonal antibodies against distinct epitopes of human B7-1.
AB  - The costimulatory molecule B7-1 (CD80) has been shown to be an important
      component for T cell immune responses. We have generated several monoclonal
      antibodies (PSRM-1, -2, -3, -6, and -7) against B7-1 using a human
      glycosylphosphatidylinositol-anchored B7-1 (GPI-B7-1) as an antigen. These
      monoclonal antibodies are able to detect B7-1 by flow cytometry, ELISA, and
      Western blotting. One antibody in particular, PSRM-3, blocks the CD28/CTLA-4
      interaction with B7-1 and consequently blocks costimulation of T cells. The other
      PSRM monoclonal antibodies did not compete with PSRM-3 for recognition of B7-1
      and also failed to block B7-1 interaction with CTLA-4 and CD28, indicating that
      these antibodies bind to different epitopes. PSRM-3 and -7 detect
      phosphatidylinositol-specific phospholipase C-released soluble GPI-B7-1 in a
      sandwich ELISA. We used this sandwich ELISA to assay for the presence of a
      soluble form of B7-1 in synovial fluids of arthritis patients. By sandwich ELISA,
      B7-1 was detected in the synovial fluid of 5/11 patients with rheumatoid
      arthritis, 5/5 patients with osteoarthritis, and 2/6 patients with other forms,
      including crystalline-induced arthritis. The presence of soluble B7-1 was
      confirmed by immunoprecipitation using PSRM-3-coupled Sepharose beads. The source
      and function of soluble B7-1 are unknown at present; it is possible, however,
      that the soluble form of B7-1 molecule may play a local immunoregulatory role
      which may suppress or induce inflammation depending upon whether it interacts
      with the T cell costimulatory CD28 molecule or the negative signaling CTLA-4
      molecule.

PMID- 9576012
TI  - A newly discovered function for C1 inhibitor, removal of the entire C1qr2s2
      complex from immobilized human IgG subclasses.
AB  - A new function for C1 inhibitor (C1 INH) is reported. C1 inhibitor dislodged the
      entire activated C1 complex (C1qr2s2) from immobilized human IgG. C1 binding to
      doses of immobilized human IgG3, IgG1, or IgG2 was quantified as a function of
      time. When human serum, as a source of C1qr2s2, was added to relatively low doses
      of immobilized IgG, C1q binding peaked at 1.0 min then gradually decreased.
      However when purified C1q was applied to immobilized IgG, C1q binding did not
      diminish with time. The removal of C1q was duplicated by adding purified C1 INH
      to C1qr2s2 which had been bound to immobilized IgG. The dislodgement of C1q from
      immobilized IgG required the presence of intact C1qr2s2 and of C1 INH. This
      removal of C1q by purified C1 INH was prevented when activated C1s was used to
      neutralize C1 INH function or when relatively high levels of IgG were
      immobilized.

PMID- 9576011
TI  - A study of the immunology of the chronic fatigue syndrome: correlation of
      immunologic parameters to health dysfunction.
AB  - Surface and intracellular immunologic and apoptotic markers and functional
      lymphocyte assays after stimulation with anti-CD3/anti-CD28 antibodies or
      phytohemagglutinin (PHA) were studied in 44 patients fulfilling the Oxford
      criteria for chronic fatigue syndrome (CFS). Results were then correlated to
      scores for the Short Form-36 health questionnaire (SF-36), which assesses eight
      aspects of patient's well-being, and for the general health questionnaire (GHQ),
      which detects current psychiatric disorder. Patients had significantly increased
      mean fluorescence intensity readings of HLA-DR in CD4 and CD8 cells (P < 0.05).
      Expression of the costimulatory receptor CD28 in CD8 cells was significantly
      reduced, and the apoptosis repressor ratio of bcl-2/bax in both CD4 and CD8 was
      increased in patients (P < 0.05). Patients with increased HLA-DR expression had
      significantly lower SF-36 total scores, worse body pains, and poorer general
      health perception and physical functioning scores. Increased spontaneous
      lymphocyte proliferation was associated with poor general health perception. PHA
      proliferative responses were lower in patients with poor emotional and mental
      health scores, and the anti-CD3/anti-CD28 response was low in those with low
      general health perception scores. Higher spontaneous proliferation and reduced
      PHA responses correlated with higher GHQ scores. Similarly, GHQ scores were
      significantly higher, indicating worse mental health, in those with lower total
      SF-36 scores and worse general and mental health scores in the SF-36
      questionnaire. Finally, higher expression of the costimulatory molecule CD28
      correlated with higher total SF-36 scores, general health perception and social
      functioning scores, and with lower role limitation due to physical health. The
      increased expression of class II antigens and the reduced expression of the
      costimulatory receptor CD28, which is a marker of terminally differentiated
      cells, lend further support to the concept of immunoactivation of T-lymphocytes
      in CFS and may be consistent with the notion of a viral etiopathogenesis in the
      illness. We report, for the first time, increased expression of the apoptosis
      repressor protein bcl-2, which may contribute to enhanced survival of activated
      lymphocytes. Using the SF-36 health assessment questionnaire and the GHQ, we
      demonstrated changes in different immunological parameters, each of which
      correlated with particular aspects of disease symptomatology.

PMID- 9576013
TI  - A novel murine model of allergic conjunctivitis.
AB  - Allergic conjunctivitis affects over 40 million patients per year in the United
      States. Here we present the first murine model that incorporates the clinical,
      cellular, and humoral parameters of allergic conjunctivitis, including a ragweed
      induced Th2-type cytokine production by lymphocytes. SWR/J mice were immunized
      with short ragweed pollen in aluminum hydroxide. Ten days after immunization,
      allergic conjunctivitis was induced by one topical application of ragweed pollen
      onto the eye. Immediate response was characterized by chemosis, redness of the
      conjuctiva, and lid edema. Histopathology and immunohistochemistry showed dense
      conjunctival infiltration with polymorphonuclear leukocytes, macrophages, and
      CD4+ T lymphocytes. In addition, ragweed-specific IgG1 and IgE serum levels were
      significantly higher in immunized animals, and high levels of IL-4 and IL-5 were
      detected in supernatants from ragweed-activated lymphocytes. This reproducible
      model is a well-suited instrument for testing the pathophysiology and future
      therapies of allergic conjunctivitis.

PMID- 9576014
TI  - Oral administration of schistosome egg antigens and insulin B-chain generates and
      enhances Th2-type responses in NOD mice.
AB  - In murine Schistosoma mansoni, parenteral administration of parasite eggs or
      saline-soluble egg antigens (SEA), generates Th2 T-cell responses to both
      schistosome-specific and unrelated third-party antigens. Oral administration of
      insulin to NOD mice suppresses or delays the onset of diabetes by skewing the
      response toward CD4+ Th2 cells and TGF-beta producing cells. From these two
      independent sets of observations, we initiated the present study to determine if
      oral administration of SEA would stimulate Th2-type cytokine responses when mice
      were fed SEA alone or in tandem with insulin B-chain. Our results show that
      feeding NOD mice with either insulin B-chain or SEA alone significantly inhibits
      proliferation to the immunizing antigen. When cytokine profiles were examined,
      feeding led to a predominance of IL-10 and TGF-beta production. Furthermore,
      feeding SEA in combination with insulin B-chain augmented the level of IL-10
      production to insulin. T-cell lines established from SEA-fed and -immunized mice
      secreted IL-4 and IL-10 cytokines whereas the T-cell lines from control-fed mice
      immunized with SEA secreted predominantly IL-2 and IFN-gamma. These results
      demonstrate that orally administered insulin can induce regulatory T-cells
      secreting IL-4, IL-10, and TGF-beta and that Th2 responses to oral insulin could
      be augmented in a synergistic way by feeding SEA and insulin B-chain together.

PMID- 9576015
TI  - Reduced CD4 and HLA-DR expression in neonatal monocytes.
AB  - Three-color flow cytometry was used to assess the immunophenotypic
      characteristics of normal cord blood monocytes after labeling with a variety of
      antibodies against myeloid/monocyte-specific markers. Monocytes both in cord
      blood and in peripheral blood from normal adults were defined in a backgating
      procedure as cells with the light-scattering characteristics of monocytes that
      also expressed CD14. The percentage of monocytes, defined in this fashion, that
      also displayed CD4 receptors was significantly lower in cord blood (mean +/- SD =
      29.3 +/- 13.9%) than in peripheral blood from normal adult controls (mean +/- SD
      = 68.9 +/- 13%) (P < 0.005). Similarly, HLA-DR expression was found on only 86 +/
      6.6% of monocytes in cord blood but on 99 +/- 1% of monocytes in adults (P <
      0.005). The percentage of monocytes displaying CD16 receptors in cord blood did
      not show any significant difference in comparison with adult monocytes. When
      coexpression of CD14, CD16, and CD4 was assessed, cord blood showed a predominant
      population of monocytes bearing the phenotype CD14+/CD16-/CD4-. Similarly,
      approximately 10% of CD14+ monocytes in cord blood expressed neither CD4 nor HLA
      DR. Cytochemically, monocytes from cord blood revealed intense granular staining
      for PAS and marginal or absent staining for nonspecific esterase (NSE). These
      results raise the possibility that reduced expression of CD4 and HLA-DR receptors
      on cord blood monocytes may contribute to their impaired immune response.
      Additionally, the high percentage of CD14+/CD16-/CD4- cells in cord blood
      suggests that these cells may represent a phenotypically immature population of
      monocytes. Likewise, the unusual cytochemical staining patterns suggest that
      these cells are biochemically immature as well.

PMID- 9576016
TI  - Suppression of viral replication in a long-term nonprogressing rhesus macaque
      experimentally infected with pathogenic simian immunodeficiency virus (SIV).

PMID- 9576018
TI  - [Value of inflammation and bone scintigraphy in differential diagnosis of painful
      affections of small joints].
AB  - It was the aim of this study to evaluate different markers of inflammation such
      as 99mTc-labelled human immunoglobulin G and 99mTc-nanocolloid with respect to
      their ability to detect inflammatory or degenerative affections of small joints
      of hand and fingers. While conventional bone scanning reveals good agreement with
      clinical findings it is not well suited for screening of inflammatory processes
      due to its poor specificity. In small joints conventional three-phase bone scan
      with information of perfusion, bloodpool and accumulation is not suitable due to
      the small ROI, low count rate with high statistics. Therefore we used
      inflammatory markers to overcome this problem. Immunoglobulin G was true positive
      in case of inflammatory lesions in 69%, and false positive in case of
      degenerative lesions in 24%, while nanocolloid was true positive in 72% and false
      positive in 14%, respectively. Significant differences were found between markers
      of inflammation and the bone scanning agent while both inflammatory markers,
      immunoglobulin G and nanocolloid demonstrated significant correlation. While bone
      scanning tracers detect all kinds of joint affections, immunoglobulin G and
      nanocolloid accumulate preferentially in inflammatory joints and therefore might
      be useful to differentiate between inflammatory and degenerative lesions.

PMID- 9576017
TI  - [Toxicity and radiation dosage of 2-(18F)-2-desoxy-D-glucose in positron emission
      tomography].
AB  - 2-[18F]-FDG, a non-physiological glucose analogue, is the most important positron
      emission- tomography (PET) radiopharmaceutical. As an example we refer to the
      production of 2-[18F]-FDG at the research center in Karlsruhe. 2-[18F]-FDG is
      synthesized in a "no carrier added" process. It is delivered at a maximal filling
      volume of 10 ml from a 14.5 ml batch with a batch-to-batch yield fluctuation from
      5075 to 50,750 MBq and a specific activity from 1 to 10 GBq/mumol. The residual
      remaining synthesis reagents like solvents or catalysts have no toxicological
      relevance. The applicated dose per patient is in a range from 185 to 370 MBq and
      1000 times lower than the correlating concentrations of stable FDG which can be
      regarded harmless in animals. 2-[18F]-FDG does not interfere with normal glucose
      metabolism. It is taken up by cells and phosphorylated to 2-[18F]-FDG-6
      phosphate. The following dephosphorylation step is slow and the labeled compound
      is retained over several hours within the cells. Non-metabolized 2-[18F]-FDG is
      excreted rapidly in the urine to an extent of about 16% after 60 min, and 50%
      after 135 min, respectively. Fluorine-18F decays by emission of 511 KeV gamma
      photons. The whole body effective dose is reported to be 21 to 27 microSv/MBq. In
      case of an intravenous injection of 370 MBq this leads to a total dose of 7.8 to
      10 mSv. The critical organ is the bladder wall (radiation dose 120 to 170
      microSv/MBq or 80 to 100 mrem/mCi). The risk of a radiation induced late
      malignoma at 10 mSv can be estimated to be 1:2000. The genetical risk as a
      consequence of FDG-PET diagnostics would be 1:100,000 to 2:100,000 for dominant,
      and 5 times higher for recessive mutations.

PMID- 9576019
TI  - Lung diffusion estimated by oxygen and carbon monoxide.
AB  - The study was objected to the comparison of the results of lung diffusion
      estimated by oxygen to those of routinely used single breath carbon monoxide
      method. The method described is based on the analysis of the speed of response of
      arterial partial oxygen pressure (paO2) to increasing inspiratory fraction of
      oxygen (Fi). The transcutaneous oximetry was used to follow paO2 by means of
      transcutaneous oxygen pressure (ptCO2). The study was performed on 35 patients of
      both sexes with interstitial lung involvement with normal or only slightly
      decreased FVC and FEV1. The close correlation between the results of both methods
      was proved (r = 0.848, p < 0.0001).

PMID- 9576020
TI  - First description of the effect of a non-sulfonylurea compound,
      tetramethylpyrazine, on coronary response to desoxyglucose-induced ischemia.
AB  - The compound 2,3,5,6-Tetramethylpyrazine (TMP; Ligustrazine), a flavouring
      component and sweetness enhancer for beverages constitutes a commonly used food
      additive. Now we studied the effect of TMP on coronary artery dilation during
      ischemia: In our experiments we used isolated, Langendorff-perfused guinea pig
      hearts, arrested with K(+)-rich Normal Tyrode solution (in mM: NaCl 129.5, KCl
      15, MgCl2 0.8, CaCl2 1.0, glucose 10), buffered with 10 mM HEPES to pH 7.4 at 37
      degrees C, equilibrated with 100% O2. Ischemia was simulated by equimolar
      replacement of glucose by 2-deoxyglucose (DOG), an inhibitor of oxydative
      phosphorylation. We found that coronary perfusion pressure (CPP) decreased by 20
      +/- 1.2 cm H2O (from initially 90 cm H2O; n = 6, +/- SEM) within 15 min from the
      onset of DOG. In the presence of 1 mM TMP the decrease in CPP was largely
      attenuated and CPP declined by 1.4 +/- 1.0 cm H2O (n = 6, +/- SEM; p < 0.01). In
      2 out of the 6 TMP experiments even as light increase in CPP (< 2 cm H2O) could
      be seen. We conclude that TMP, a blocker of ATP-dependent K(+)-channels in
      pancreatic beta-cells and possibly in arterial smooth muscle cells, prevents
      coronary dilation in response to ischemia. The possible suppression of this vital
      mobilization of coronary reserve during ischemia in patients with coronary artery
      disease certainly merits further attention and may question the use of this
      compound as a food additive.

PMID- 9576021
TI  - [Management of HIV infected patients: applicability of guidelines. Results of an
      nationwide Austrian survey].
AB  - BACKGROUND: Antiretroviral treatment and prophylaxis in HIV-infected patients
      follows guidelines. Aim of the study was to evaluate to what extent guidelines
      are useful. We used a cohort of patients (I) and a nationwide audit (II).
      SUBJECTS AND METHODS: Over a 48-month period demographic data, immunologic
      function and stage of HIV-infection of 433 patients were recorded (I).
      Questionnaires about the practicability of antiretroviral therapy according to
      recently published guidelines were mailed to experienced hospital departments and
      private offices (II). RESULTS: I. In 307 of 433 (70.9%) patients antiretroviral
      therapy and in 107 of these 433 (24.7%) patients primary prophylaxis against PC
      infection could be initiated according to the guidelines. In 21 of 433 patients
      (4.8%) Ganciclovir prophylaxis was applicated using Port-a-Cath systems in a
      homecare setting. II. In Austria 118 questionnaires were mailed in June 1996, 43
      (36.4%) were returned and 38 could be evaluated. 1450 patients were treated by
      physicians, who answered the questionnaires, 78.1% of these worked in hospitals
      and 78.9% were specialists. 75% of the physicians had experience with HIV
      infected patients exceeding 5 years. CD4+ lymphocyte count was routinely done in
      73.7% of the physicians, viral load only in 42.1%. These examinations were
      predominantly performed in hospitals (in 64.3% and 81.2%, respectively). Only
      13/36 of the physicians prescribed the recommended combination therapy consisting
      of 2 nucleosides and 1 protease-inhibitor. 5/6 hospitals and 4/8 private offices
      in Vienna and 6/12 hospitals outside of Vienna used proteaseinhibitors.
      CONCLUSIONS: Antiretroviral treatment according to the guidelines published
      recently, is only possible in centres for the treatment of HIV-infected patients
      at the moment.

PMID- 9576022
TI  - [Clinical gait analysis--methods, limitations and possible applications].
AB  - Human gait is a complex and cyclic movement. Gait analysis of human walking can
      be done either without any technical support, or in combination with complex and
      expensive equipment. Modern gait analysis is based on the integration of multiple
      components to derive a complete analysis of gait. These methods may include
      observation, videotaping, electromyography, kinematics, kinetics and energetics.
      The results gained from these methods may then be used to determine the treatment
      course of a subject with gait abnormalities or to document the effects of
      therapeutical intervention. The purpose of this article is to provide an overview
      of the most common used methods in gait analysis. Emphasis will be placed on the
      type of information that can be derived from each component and how this
      information can be used clinically.

PMID- 9576023
TI  - [Thymopentin in alopecia areata].
AB  - Alopecia areata is a common cause of hair loss which leads to localized bald
      areas predominantly on the scalp. Etiological factors are not clear yet, but it
      is generally considered as a consequence of an autoimmune process. Histological
      findings revealed perifollicular infiltration of T-cells and antigen-presenting
      cells. Autoreactive T-cells are reported to amplify this abnormality by
      interacting with follicular epithelium. There is no effective treatment available
      at the moment. We report on a 53-year old climacteric woman who developed a bald
      lesion on her scalp spontaneously in november 1995. Alopecia areata was
      documented before and after therapy. Treatment with thymopentin 50 mg
      subcutaneously was offered successfully for 10 weeks, while continuing hormone
      replacement therapy. Other therapeutical strategies did not proof to be
      successful before.

PMID- 9576025
TI  - Effects of hepatic HDL-related mRNAs on plasma prebeta HDL in cholesterol-fed
      rabbits.
AB  - This study was undertaken to determine; 1) the effect of cholesterol enriched
      diet on prebeta-migrating (prebeta) HDL levels, 2) the effect of the diet on
      plasma proteins and/or activities likely associated with prebeta HDL (cholesteryl
      transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT) and
      apolipoprotein (apo)A-I), 3) the effect of the diet on the corresponding hepatic
      mRNAs and 4) the correlation between the hepatic mRNAs and prebeta HDL. Rabbits
      were fed 0.1% (low) cholesterol (LC group, n = 6) or 0.5% (high) cholesterol diet
      (HC group, n = 6) for 6 weeks. Plasma CETP activities, plasma total apoA-I and
      prebeta apoA-I concentrations in the HC group were significantly increased (58.95
      +/- 2.37%, 191.52 +/- 13.93 mg/dl, 44.21 +/- 1.14 mg/dl, respectively) compared
      with the LC group (39.36 +/- 3.62%, 152.85 +/- 8.61 mg/dl, 30.12 +/- 2.79 mg/dl,
      respectively)(p < 0.05). Plasma LCAT activities did not differ significantly
      (56.65 +/- 7.19 vs 57.41 +/- 8.21; HC vs LC). Hepatic CETP, LCAT and apoA-I mRNA
      levels were determined using reverse transcription polymerase chain reaction (RT
      PCR). Hepatic CETP mRNA levels, compared to GAPDH mRNA levels as a control, were
      increased in the HC group (2.226 +/- 0.115) compared with the LC group (1.649 +/-
      0.170) (p < 0.05), while hepatic LCAT and apoA-I mRNA levels were unchanged.
      Thus, plasma concentration of prebeta HDL, CETP activity and the amount of
      hepatic CETP mRNA were increased in response to the dietary intake of
      cholesterol. Multiple regression analyses showed that only hepatic CETP mRNA
      levels had a positive correlation with plasma prebeta HDL concentration (p =
      0.04). These results indicate that individual variations in hepatic CETP mRNA
      levels in rabbits fed a cholesterol diet probably has a major influence on the
      determination of plasma prebeta HDL concentration.

PMID- 9576024
TI  - Drug induced contraction and relaxation in mouse isolated aorta.
AB  - Possibility of using mouse isolated aorta to evaluate the effect of vasoactive
      agents was demonstrated. The results suggested that aortic contraction induced by
      the alpha adrenoceptor agonist norepinephrine was sensitive to prazosin, and the
      contraction induced by the membrane depolarization agent KCl was sensitive to
      verapamil. Clonidine acting as a partial agonist attenuated the norepinephrine or
      methoxamine induced contraction. Both IBMX and nitroprusside relaxed the aortic
      contraction. These vascular changes induced by the above vasoactive agents in
      mouse isolated aorta were similar to those of rat described elsewhere. The
      present findings suggested that mouse isolated aorta can be used as a tool to
      test the effect of vasoactive agents.

PMID- 9576026
TI  - Lipoprotein abnormalities in non-insulin dependent diabetic patients with
      ischemic heart disease.
AB  - Plasma lipoproteins and clinical characteristics of non-insulin-dependent
      diabetic mellitus (NIDDM) patients with (n = 50) and without (n = 108) ischemic
      heart disease (IHD) were compared. The patients with IHD were older (64 +/- 9 vs
      59 +/- 9 years, mean +/- SD, P < 0.01) and had a longer duration of diabetes (14
      +/- 9 vs 11 +/- 8 years, P < 0.05). Lipids, lipoproteins and apolipoproteins were
      comparable in the two groups. The percent distribution of triglycerides (TG) in
      the very low density lipoprotein (VLDL) fraction was significantly higher (55 +/-
      16 vs 50 +/- 17%, P < 0.05). The level of low density lipoprotein (LDL) (33 +/-
      14 vs 39 +/- 15%, P < 0.05) and the apo E/VLDL-TG ratio (0.085 +/- 0.045 vs
      0.12070.097, P < 0.01), however, was significantly lower in patients with IHD
      than in those without IHD. Multiple regression analysis also indicated that age,
      duration of diabetes, percent distribution of TG in VLDL, percent distribution of
      TG in LDL and the apo E/VLDL-TG ratio were significantly related to the presence
      of IHD. Hypertriglyceridemia, particularly when characterized by abnormalities of
      TG distribution, may play an important role in the development of IHD in NIDDM
      patients.

PMID- 9576027
TI  - [The status of trauma surgery management in Germany. Position of the Covenant of
      Chief Hospital Physicians in Surgery on the intended changes in professional
      treatment].

PMID- 9576028
TI  - [Surgical emergency aid in civil war areas].

PMID- 9576029
TI  - [The new transplantation law. What must hospital physicians observe?].

PMID- 9576030
TI  - [Decreased medical performance or lowering the standard? From the view point of
      the German Hospital Society].

PMID- 9576031
TI  - [The confusing track of Helicobacter].

PMID- 9576032
TI  - [Helicobacter '98--epidemiology and significance in carcinogenesis].
AB  - Gastritis caused by infection with Helicobacter pylori is one of the most common
      infectious diseases worldwide. There are data on the epidemiology,
      pathophysiology and histology of this disease that show that Helicobacter pylori
      gastritis plays an important role in gastric carcinogenesis. However, we must
      remember that only a very few among those infected with Helicobacter pylori will
      develop gastric cancer. Hence, one of the main targets of future research will be
      to identify individuals who carry a greater risk for developing gastric cancer
      and may therefore benefit from eradication of Helicobacter pylori in terms of
      gastric cancer prevention.

PMID- 9576033
TI  - [Helicobacter pylori infection and ulcer].
AB  - Our understanding of ulcer pathogenesis has dramatically changed since the
      discovery of Heliobacter pylori. Peptic ulcer is now recognized as a chronic
      gastric infectious disease. H. pylori can be considered the pacemaker, with other
      known risk factors ultimately contributing to the ulcer formation. Treatment of
      H. pylori in peptic ulcer disease cures the acute lesion and prevents relapse and
      complications. In clinical management a positive diagnosis of H. pylori is
      required and other potential causes for ulcer formation must be excluded before
      starting treatment. The standard treatment in H. pylori positive ulcer consists
      of PPI in standard dose and two antibiotics either clarithromycin 2 x 500 mg and
      amoxycillin 2 x 1 g or metronidazole 2 x 400 mg and clarithromycin 2 x 250 mg (or
      500 mg) for 7 days. The simultaneous presence of H. pylori and NSAID intake
      requires distinct management. Following bleeding complication a PPI needs to be
      given beyond 7 days until ulcer healing is endoscopically confirmed.

PMID- 9576034
TI  - [Helicobacter and lymphoma].
AB  - The gastrointestinal tract represents the most common extranodal site of
      malignant non-Hodgkin's lymphoma. Epidemiological, histomorphological, molecular
      biological and experimental animal studies undoubtedly underline the important
      role of Helicobacter pylori for the development and progression of primary
      gastric lymphoma of MALT (mucosa-associated lymphoid tissue). Eradication of
      Helicobacter pylori is an important therapeutic option in low-grade gastric, MALT
      lymphoma of localized stage E I.

PMID- 9576035
TI  - [Radiotherapy in surgical and nonsurgical patients. Therapy expectations, quality
      of life and physician assessment].
AB  - The present study investigates patients' expectations toward radiotherapy and
      their associations to quality of life and physician judgements. Fifty-five
      patients with tumors of different sites (30 with previous tumor-related surgery,
      25 without surgery) admitted to the department of radiotherapy filled out a
      standardized questionnaire (EORTC QLQ-C30, PLC by Siegrist et al., therapy
      related expectations and success) before and after inpatient radiotherapy. The
      corresponding physician ratings were collected. Fifty-eight percent of the
      patients expected the therapeutic goal "healing", whereas from the physician's
      standpoint this was realistic in only 7% of cases. The specific radiotherapy
      related expectations "tumor control" and "pain relief" reached almost the same
      levels in patients and physician (71% vs 71% and 40% vs 44%). Patients with
      healing expectancy reported higher quality of life at the beginning of the
      therapy (53.4% vs 39.9%); patients expecting pain relief reported lower quality
      of life (37.1% vs 54.5%). Surgical patients who had been operated on within the
      past year (n = 18) showed a particularly high healing expectancy (83%), whereas
      patients whose operation dated back more than 1 year focused on pain relief as
      therapeutic goal (83%). The surgeon, as the primary contact person for patients,
      can influence patients' therapy-related expectations. In explaining the overall
      therapeutic strategy, surgeons should also mention the scope and limits of
      adjuvant therapies.

PMID- 9576036
TI  - [Early stomach carcinoma--pathologic-anatomic findings and prognosis].
AB  - BACKGROUND: The therapy for early gastric cancer (endoscopy, gastric resection,
      D1/2 dissection) is controversial. MATERIALS AND METHODS: In a retrospective
      study (4/86-12/95) we analyzed the prognosis of 57 early gastric cancer patients
      with respect to pathological findings and surgical therapy. RESULTS: The R0
      resection rate was 100%. In 7% multifocal tumor growth was seen. The 5-year
      survival rate was 70%. LN-metastases were found in 12% of all cases, more often
      in pT1b than in pT1 a tumors (17 vs 9%) and more often in large carcinomas than
      in small carcinomas (> 1000 mm2: 27%; < 300 mm2: 0%). Long-term survival was
      significantly better in pN0 patients than in patients with LN metastasis (P =
      0.020). CONCLUSION: Prognosis of early gastric cancer after curative resection is
      good.

PMID- 9576037
TI  - [Clinical and imaging aspects of gallstone ileus. Experiences with 108 individual
      observations].
AB  - Cases of gallstone ileus (108) were analyzed retrospectively over 30 years. Even
      today, when laparoscopic cholecystectomy is done, the incidence of this rare
      disease remains the same. History, clinical and X-ray findings are non-specific.
      Aerobilia was seen in 17% of the patients. Since 1992 sonography has provided an
      exact diagnosis in 10 of 15 cases. In the triad of known gallstone, non-specific
      epigastric pain with assumed small intestinal obstruction, and impossible
      detection of a stone in the gallbladder, there is strong suspicion of a gallstone
      ileus. The evidence is given if the gallstone is seen in the bowels.
      Intraoperatively more than one stone was found in the intestines in 20%, and
      cholecystoduodenal fistulas were encountered in 83%. Other fistulas are rare.
      There has been no significant change in mortality for 30 years.

PMID- 9576038
TI  - [Ultrasound criteria of gallstone ileus].
AB  - During a 4-year period we treated four patients with gallstone ileus by
      enterotomy and extraction of the impacted concrement. Diagnosis was quickly
      established by abdominal ultrasound examination in all cases. Lacking visibility
      of the gallbladder in the clinical setting of ileus and subileus proved to be a
      sonographic clue of gallstone ileus and prompted a thorough search for the
      obturating gallstone which could definitely be demonstrated as an intraluminal
      semicircular reflex with strong echos and a sonic shadow in all patients. Thus,
      due to early diagnosis and timely surgical intervention, even in the absence of
      full-blown ileus, all of our elderly patients and those with a multitude of
      diseases still had a favorable outcome.

PMID- 9576039
TI  - [Artifactual illness in plastic surgery].
AB  - The therapy of factitious disorders is a challenge for the treating surgeon. Only
      a clear understanding of the underlying causes and a good doctor-patient
      relationship make a successful outcome possible. Discussion about a confrontation
      of the patient with the diagnosis and the best made of treatment is still in
      progress. Early diagnosis and the cooperation between surgeons and psychiatrists
      are the most important parts of dealing with factitious disorders. This article
      gives an overview of symptoms and therapies. Six case reports demonstrate
      possibilities of the disorder's appearance.

PMID- 9576040
TI  - [Open pelvic fracture--an indication for laparotomy?].
AB  - Open pelvic fractures are rare and account for 1-5% of all pelvic fractures.
      Mortality rates of 50% and even more have been reported. Bleeding and septic
      complications are the major causes of death. In our retrospective study from 1974
      to 1996 the data of 40 patients were analyzed. Five patients died (12.5%); 28
      survivors could be investigated with a mean follow-up of 10 years. It is
      concluded that the comparably low mortality rate is due to a standardized
      treatment protocol. The main principles of management are emergency stabilization
      of the unstable pelvis and early laparotomy.

PMID- 9576041
TI  - [Pigmented villonodular synovitis. Case reports and review of the literature].
AB  - Because this disease is so rare the optimum treatment of pigmented villonodular
      synovitis (PVNS), in particular the diffuse form differs in the literature. The
      most important surgical procedures are arthroscopic and open synovectomy. The
      prevention of disease progression, as well as joint destruction and dysfunction,
      depends upon the early diagnosis of PVNS. During 1994 and 1995, we treated four
      cases of PVNS surgically and followed the patients for a time period of more than
      12 months. Two patients were treated with complete synovectomy, one patient
      underwent partial synovial resection, and in the final case an arthrodesis was
      performed. Our results indicate that an MRI is essential for diagnosis and
      treatment planning. For the localized form of PVNS, it appears that a partial
      synovectomy is appropriate. However, in the event of diagnostic uncertainty or
      obvious diffuse involvement of the synovium, a total synovectomy is indicated
      because of the high recurrence rate. In our study, all four patients had disease
      involving secondary bony lesions and, in one case, joint destruction. Based on
      our findings, it is clear that early surgical therapy is the only recommended
      curative intervention. The decision regarding the surgical approach, arthroscopic
      versus open, depends on the form of PVNS, the extent of the disease and secondary
      changes of the joint.

PMID- 9576043
TI  - [Monstrous pseudocyst of the adrenal gland].
AB  - We report on a 64-year-old patient with a huge adrenal pseudocyst. These are rare
      cystic lesions of the adrenal gland with an unclear etiology. Recent studies
      suggest that the majority of adrenal pseudocysts are of vascular origin. All
      cystic masses in the epigastric region have to be considered in the differential
      diagnosis. The treatment of choice is surgical removal.

PMID- 9576042
TI  - [Pancreas transplantation with bladder and intestinal drainage technique with
      systemic-venous and initial experiences with portal venous drainage. Which
      technique can be recommended today?].
AB  - The experience worldwide with pancreas transplantation includes more than 9000
      cases. In the most popular patient group (simultaneous pancreas-kidney
      transplantation, SPK) the graft-function rate at 1 year now reaches more than
      80%. More than 90% of all pancreas transplants were performed using the bladder
      drainage technique (BD) with systemic venous anastomosis. Late problems with the
      BD require enteric conversion in 10-20% in the long term. In the present study we
      report the results of 40 SPK using the BD (n = 20) and enteric drainage (ED)
      techniques (n = 20). After 3 months, the patients pancreas and kidney survival
      rates in the BD group were 100, 95 and 100% and in the ED group 100, 100 and
      100%, respectively. No anastomosis leakage occurred in either group. In two cases
      of the ED group the pancreas grafts were drained portal venously via the superior
      mesenteric vein without surgical complications. With growing experience,
      excellent SPK results can be reached with both the BD and ED techniques.

PMID- 9576045
TI  - [Rupture of a Baker cyst with compartment syndrome. A rare complication of knee
      arthroscopy].
AB  - We report a case of leakage of irrigation fluid into the extra-articular soft
      tissue, due to rupture of a Baker's cyst during arthroscopy of the knee joint. A
      four-quadrant fasciotomy of the calf musculature was performed to prevent the
      devasting ischemic complications of an imminent compartment syndrome. A survey of
      the literature reveals no consensus regarding the treatment of such
      complications. On the contrary, some authors recommend avoiding fasciotomy and
      waiting for spontaneous reabsorption of the irrigation fluid.

PMID- 9576044
TI  - [Primary non-Hodgkin lymphoma of the pancreas].
AB  - A 71-year-old patient had been suffering from pain-free obstructive jaundice for
      8 weeks. Ultrasonography and computed tomography revealed an inhomogeneous mass
      (diameter 7 x 6 cm) in the head of the pancreas. In combination with a CA 19-9 of
      329 U/l, the findings were highly suggestive of a pancreatic carcinoma.
      Endoscopic implantation of a pigtail drain into the dilated choledochal duct was
      performed. A partial duodenopancreatectomy (Whipple's procedure) became necessary
      because of continuous bleeding with hemodynamic disorders after endoscopic
      papillotomy. In the histopathological examination a low-grade malignant non
      Hodgkin lymphoma of the pancreas (follicular centroblastic-centrocytic) was
      diagnosed. The differential diagnosis of primary pancreatic lymphoma from
      pancreatic carcinoma is usually impossible. Neither clinical nor laboratory nor
      imaging methods indicate to the correct diagnosis. In cases of relatively large
      pancreatic tumor masses and impression of the pancreatic duct without
      infiltration, a primary pancreatic lymphoma should be considered and a
      histological diagnosis by biopsy should be performed.

PMID- 9576046
TI  - [Fundus rotation gastroplasty].

PMID- 9576047
TI  - [Ambulatory laparoscopic cholecystectomy].

PMID- 9576048
TI  - Epidemiology of HIV and AIDS. A retrospective look.
AB  - This retrospective look at literature and information regarding the epidemiology
      of HIV and its progression to AIDS is based on many worldwide sources to
      determine with some certainty the true severity of the epidemic. The purpose of
      this article is to permit the reader to become more informed concerning the
      epidemic, based on a global outlook.

PMID- 9576049
TI  - Molecular biology of HIV.
AB  - This article describes the molecular aspects of the life cycle of HIV. Evolution
      theories of HIV origin, specific steps in the infection cycle, and regulation of
      expression are discussed. The article concludes with a summary of the current
      theories of the pathogenesis of HIV infection and the breakdown of the immune
      system.

PMID- 9576050
TI  - Legal implications of treating HIV patients.
AB  - A patient's HIV status often has significant impact on a physician's willingness
      and ability to provide quality medical care. A physician may face substantial
      penalties for refusing to treat a patient who has HIV. Even the referral of a
      patient with HIV to an HIV specialist may constitute a discriminatory act. The
      law provides certain guidelines that, if followed, may keep a physician out of
      the courtroom.

PMID- 9576051
TI  - Antiretroviral therapies.
AB  - The use of a combination of more potent antiretroviral agents has resulted in
      suppression of HIV replication to undetectable levels in many patients. Three
      classes of antiretroviral drugs are currently available: nucleoside reverse
      transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and
      protease inhibitors. A new class of agents, nucleotide reverse transcriptase
      inhibitors, is expected to be available soon. Clinical studies and indications
      providing the rationale for use of these agents, contraindications, drug
      interactions, and adverse reactions are discussed.

PMID- 9576052
TI  - Medications in the treatment of HIV: associated conditions.
AB  - The current focus of HIV care is on maximizing the efficacy of drugs that inhibit
      HIV replication. Unlike the simpler and less effective antiviral regimens used
      until recently, these multiagent cocktails are more effective yet pose greater
      risk for drug interactions. Because of the complexity of these drug interaction
      issues, it is critical that podiatric consultants communicate with the primary
      care physician when medication changes are anticipated. In addition,
      pharmacologic consultation is readily available [see Antivirals section] via an
      800 number to assist all medical providers in adjusting medication regimens to
      prevent adverse drug interactions. As the majority of patients infected with HIV
      live longer, they likely are to be maintained on complex, multidrug regimens. For
      those patients who do not respond to current antiviral therapies and, hence, are
      at risk for opportunistic malignancies and infections, multiagent regimens often
      used with antiviral therapy will continue to be necessary.

PMID- 9576053
TI  - The podiatric examination.
AB  - With the evolution of the AIDS epidemic into a relatively chronic disease,
      practitioners will continue to see an increase in the number of patients infected
      with HIV for the diagnosis and management of podiatric pathology. A thorough
      history and physical examination, taken with a complete knowledge base of HIV
      implications, will enhance the ability to form the strategies required to treat
      the manifestations of this disease and to request appropriate referrals.
      Laboratory studies and other diagnostic techniques have been developed and
      increased in specificity to allow for earlier and more precise identification of
      the presenting pathology. A continuously expanding choice of medications is
      available for treatment. The clinical presentations of HIV infection in the foot
      involve nearly all organ systems. This article reviews the podiatric role as part
      of the medical team in the diagnosis and treatment of patients infected with HIV.

PMID- 9576054
TI  - Neurologic problems of the lower extremity associated with HIV and AIDS.
AB  - Lower extremity symptoms are caused by lesions at any level of the neuraxis, from
      cortex to muscle. HIV affects virtually every level of the nervous system, either
      directly or indirectly. The presence of pathology at multiple levels and by
      multiple processes further complicates the bedside diagnosis of a patient with
      AIDS and neurologic symptoms. Many neuropathies and other conditions that affect
      the lower extremities can be identified with careful history and physical
      examination, confirmed with limited testing, and can be treated successfully.
      Distal symmetric polyneuropathy is the most common lower extremity disorder, but
      it must be distinguished from similar-appearing neuropathies caused by
      medications, B12 deficiency, or vasculitis. Diffuse infiltrative lymphocytosis
      syndrome also causes a painful peripheral neuropathy that must be distinguished
      from distal symmetric polyneuropathy. Inflammatory demyelinating polyneuropathies
      are characterized by muscle weakness. They occur in early, asymptomatic HIV
      infection and respond to plasmapheresis or steroids. Mononeuropathies in patients
      with CD4 counts more than 200 often resolve on their own. Multiple
      mononeuropathies, which occur in patients with CD4 counts less than 50, are often
      associated with cytomegalovirus infection and may follow a rapidly progressive
      course unless treated promptly and aggressively. Progressive polyradiculopathy
      occurs late in the course of AIDS, is often caused by cytomegalovirus, is rapidly
      progressive, and generally is fatal unless recognized and treated promptly.
      Muscle weakness, myalgia, and fatigue are common in HIV and have multiple causes.
      Lower extremity spasticity may be caused by treatable etiologies such as spinal
      cord abscess, tumor, disc compression, B12 deficiency, or ischemia. Gait
      disturbances are common but nonspecific and may be caused by treatable neurologic
      disorders at any level of the neuraxis.

PMID- 9576055
TI  - Onychomycosis in HIV-positive patients.
AB  - Onychomycosis is a common podiatric condition that has become an increasing
      problem as the number of patients with HIV infection has grown. Although it is
      not among the most severe infections that affect HIV-positive patients, it tends
      to be more extensive, refractory to treatment, and has a unique clinical
      presentation in this patient population. It is important for the podiatric
      physician to be aware of the epidemiology, clinical presentation, diagnosis, and
      treatment of onychomycosis in HIV-positive patients.

PMID- 9576056
TI  - Plantar verrucae and HIV infection.
AB  - No single treatment of plantar verrucae has proven to be effective in all
      situations, which represents a greater challenge when treating patients infected
      with HIV. In this patient population, plantar verrucae appear to be more
      aggressive, and recurrence is frequently observed. Mosaic-type plantar verrucae,
      which are usually more resistant to treatment, are common in this population.
      Factors including the patient's general health, number of warts, location of
      warts, effect of lesions on daily activities, and sensitivity should be carefully
      analyzed before deciding on a treatment option. Among the many treatment
      modalities available for plantar verrucae, three frequently are used by
      podiatrists for patients infected with HIV: Histofreezer cryotherapy, bleomycin
      sulfate intralesional injections, and surgical intervention by curettage. These
      three modalities are recommended; however, all approaches described in this
      article should be kept as viable options. The patient population infected with
      HIV represents a unique group of patients, and choices in treatments for these
      patients should be made by taking into account all ramifications of HIV
      infection.

PMID- 9576057
TI  - Physical therapy management for the patient with HIV. Lower extremity challenges.
AB  - Disability assessment and rehabilitation intervention have implications for
      specific stages of HIV disease, with the intention of maximizing overall function
      and decreasing the burden of care. The AIDS epidemic has challenged communities
      to develop and to mobilize care networks for persons infected with HIV. A major
      part of that mobilization has been a push toward community and home-based
      services. Reliable and valid functional assessment data are necessary to evaluate
      HIV-related disability changes over time for patients in the hospital and at
      home. Epidemiologic data also hold implications for rehabilitation healthcare
      workers in terms of expertise in HIV-specific areas and on the staffing level.
      Access to rehabilitation services will need to be considered by public
      policymakers and financial concerns will need to be explored. Because individuals
      with HIV and AIDS are living longer and with greater levels of health, the
      chronicity of the disease warrants community support and long-term care. Various
      functional and quality-of-life measures can assist in the development of
      resources and medical interventions. As survival increases, rehabilitation
      professionals can anticipate more referrals for the assessment and management of
      physical disability in persons with HIV infection. A critical task for health
      service research is to ensure that HIV healthcare settings deliver optimum
      services at reasonable costs. Optimal care requires maximizing autonomous
      functioning and reducing periods of disability and dependence.

PMID- 9576058
TI  - Prevention of exposure to bloodborne pathogens.
AB  - This article is an overview of the bloodborne pathogen standard for podiatric
      practice. Included are the history of regulation, prevention measures to be
      undertaken in medical practice for the transmission of bloodborne pathogens, and
      measures for appropriate follow-up, should exposure occur. Physical, chemical,
      thermal, and procedural barriers against transmission and recommendations for the
      development of an office infection-control program are discussed.

PMID- 9576059
TI  - Occupational exposure to HIV, hepatitis B, hepatitis C, and tuberculosis.
AB  - This article reviews risk of occupational exposure to bloodborne pathogens,
      specifically HIV, hepatitis B, and hepatitis C to healthcare workers. Information
      regarding assessing the risk of exposure, appropriate actions to take if an
      exposure occurs, the most recent recommendations for treatment and follow-up
      postexposure, and prevention strategies for avoiding exposure are presented.
      Additionally, current recommendations for the prevention of the transmission of
      tuberculosis in healthcare workers and the regulatory guidelines governing this
      topic are discussed.

PMID- 9576060
TI  - Cytokines, growth factors and osteoclasts.
AB  - Osteoclasts, the main protagonists involved in bone resorption mechanisms, are
      generally considered to be of haematopoietic origin, although the exact nature of
      the primary osteoclastic stem cells is still unknown. In vitro cellular models
      developed to study the different events of osteoclastic differentiation have
      revealed that not only several cell types (osteoblasts, monocytes, lymphocytes,
      etc.) but also many soluble factors (cytokines, hormones, vitamins, ions, etc.)
      and extracellular matrix elements (osteopontin, osteocalcin, etc.) are involved
      in osteoclastic differentiation and activation. This article provides an
      exhaustive review of recent knowledge on the origin of the osteoclast and the
      main substances involved in the osteoclastogenesis and activation of these cells.

PMID- 9576061
TI  - Gene structure, cDNA cloning, and expression of the rat cytokine-induced
      neutrophil chemoattractant-2 (CINC-2) gene.
AB  - Cytokine-induced neutrophil chemoattractant-2 (CINC-2) belongs to the CXC
      chemokine family and consists of two isoforms, CINC-2 alpha and CINC-2 beta. We
      have studied the genomic organization and expression of the CINC-2 gene. The gene
      spans approximately 14 kb and is composed of three common exons, one CINC-2 alpha
      specific exon and two CINC-2 beta specific exons. This finding suggests that two
      isoforms of CINC-2 are encoded by mRNAs produced by alternative splicing. Each
      isoform is encoded in four exons, and exon-intron boundaries are placed
      identically within the aligned sequences of CXC chemokines. The CINC-2 alpha
      specific exon encodes an extra C-terminal serine residue, in addition to three
      amino acid residues (DKS) which were determined from amino acid sequence analysis
      of CINC-2 alpha previously. The 5' flanking region of the gene contains a TATA
      box and putative binding sites for NF-kappa B and AP-1. Northern blot analyses
      showed that the mRNA level for CINC-2 was very low in rat peritoneal macrophages
      without stimulation and increased up to 4 h after lipopolysaccharide stimulation,
      similar to that for CINC-1 or CINC-3. Thereafter, the mRNA expression decreased
      gradually. However, the mRNA level of CINC-2 remained high 24 h after
      stimulation, in contrast to that of CINC-1 or CINC-3. These data indicate the
      expression of CINC-2 is regulated differently among the CINCs.

PMID- 9576062
TI  - Tumour necrosis factor-alpha-dependent regulation of prostaglandin endoperoxide
      synthase-2.
AB  - Tumour necrosis factor alpha (TNF-alpha)-mediated regulation of prostaglandin
      endoperoxide synthase-2 (PGHS-2) mRNA levels was examined in murine fibrosarcoma
      MCA-101 cells. We demonstrated that the formation of prostaglandin E2 (PGE2) is
      highly dependent on the expression of PGHS-2 enzyme in these cells. TNF-alpha
      induced PGE2 production was evident after 12 h and was associated with a
      significant TNF-alpha-mediated increase in PGHS-2 immunoreactive protein. A
      specific PGHS-2 inhibitor, NS-398, completely abolished the TNF-alpha-mediated
      increase in PGE2 production, suggesting that the PGE2 formed in response to TNF
      alpha was derived from PGHS-2. TNF-alpha-mediated PGHS-2 mRNA accumulation was
      observed at 1 h, remained elevated for 24 h, and was blocked by actinomycin D,
      indicating that TNF-alpha increases PGHS-2 gene transcription. A significant post
      transcriptional mechanism also contributed to the increased PGHS-2 mRNA
      accumulation as the mRNA half-life was approximately 4-5 h in TNF-alpha
      stimulated cells. Inhibition of protein tyrosine phosphatases (PTPs) and protein
      tyrosine kinases (PTKs) inhibited the TNF-alpha-mediated increase in PGHS-2 mRNA
      levels. We suggest that PTPs and PTKs play a role in the transcriptional and/or
      post-transcriptional mechanisms that contribute to the regulation of the PGHS-2
      gene by TNF-alpha.

PMID- 9576063
TI  - Interferon alpha primes early proliferative response of bone marrow cells in
      vivo.
AB  - Using colony-forming assays, a number of previous studies established that
      interferon alpha (IFN-alpha) could cause bone marrow cell (BMC) suppression. In
      this study, the suppressive effect of IFN-alpha is however shown to be time
      dependent, occurring only 7-8 days after transfer of BMC obtained from IFN-alpha
      treated mice to growth factor-containing culture medium. In contrast, in the
      interval before suppression is observed, BMC obtained from IFN-alpha-treated mice
      initially proliferated more rapidly than BMC from placebo-treated mice. These
      findings suggest that IFN-alpha acts in vivo to prime the proliferative responses
      of BMC, a hitherto unexpected action which may have clinical relevance.

PMID- 9576064
TI  - Lack of IL-10 and IL-13 production by human polymorphonuclear neutrophils.
AB  - The ability of polymorphonuclear neutrophils (PMN) to produce and release
      numerous pro-inflammatory cytokines is now established and play an important role
      in triggering and maintaining the inflammatory response. We studied the autocrine
      downregulation of this process by investigating the potential production by human
      PMN of two major anti-inflammatory cytokines, interleukin 10 (IL-10) and IL-13.
      The authors' PMN purification method, based in part on immunomagnetic depletion,
      allows the elimination of all cells known to produce those two cytokines. A wide
      range of activation conditions were tested and kinetic studies were done. IL-10
      and IL-13 proteins were not detected in culture supernatants or cell lysates of
      PMN from 13 healthy volunteers. This was confirmed by the absence of IL-10 and IL
      13 mRNA expression, as shown by RT-PCR. Human PMN thus seem unable to produce or
      release two of the most potent anti-inflammatory cytokines, IL-10 and IL-13. This
      could partly account for the persistence of local inflammation, where PMN are the
      main infiltrating cells.

PMID- 9576065
TI  - Identification of macrophage migration inhibitory factor (MIF) in human vascular
      endothelial cells and its induction by lipopolysaccharide.
AB  - Cytokines play an important role in inflammation and immunity. In this study, the
      authors examined expression of macrophage migration inhibitory factor (MIF) in
      vascular endothelial cells, using human umbilical vein endothelial cells (HUVEC),
      by reverse transcription-polymerase chain reaction (RT-PCR)/Southern blot,
      Western blot analysis, and immunohistochemistry. The RT-PCR/Southern blot showed
      that MIF mRNA was exceedingly upregulated by the stimulation of
      lipopolysaccharide (LPS) and reached the maximum 12 h after the stimulation. At
      the range of 10 pg/ml to 10 ng/ml of LPS, the MIF mRNA expression was induced in
      a dose-dependent manner, but drastically decreased at doses of more than 100
      ng/ml. Western blot analysis and immunohistochemistry using an anti-human MIF
      antibody revealed the presence of MIF protein in cytoplasm of the unstimulated
      cells. The precise pathophysiological role of MIF in HUVEC has not been fully
      understood; however, the upregulation of MIF mRNA expression in vascular
      endothelial cells by LPS stimulation suggests the possibility that the cytokine
      plays an important role in systemic inflammatory events such as endotoxaemia.

PMID- 9576066
TI  - Local expression of cytokine mRNA in spleen and Peyer's patches of rats is
      involved in resistance against infection with Yersinia enterocolitica.
AB  - The immune-response against infection with Yersinia enterocolitica was studied in
      a rat model which resembles yersiniosis in humans. Lewis, Fischer and Brown
      Norway rats were inoculated with Y. enterocolitica and the cytokine mRNA
      expression in spleen and Peyer's patches was determined. In Brown Norway rats the
      infection was mild and Yersinia enterocolitica was fully cleared. In these rats
      the highest anti-inflammatory cytokine expression was found probably resulting in
      a protective host defence against the infection. In both the Lewis and Fischer
      rats Y. enterocolitica persisted. The anti-inflammatory cytokine expression was
      less pronounced in these two rat strains. The authors conclude that progression
      of disease, persistence of infection and development of reactive arthritis, may
      be related to the local expression of specific cytokines.

PMID- 9576067
TI  - Production and in situ localization of cutaneous tumour necrosis factor alpha
      (TNF-alpha) and interleukin 6 (IL-6) following skin sensitization.
AB  - The induction of contact sensitization and other cutaneous immune responses is
      dependent upon the activity of epidermal cytokines. One such, keratinocyte
      derived tumour necrosis factor alpha (TNF-alpha), is thought to provide the
      stimulus for the migration of Langerhans cells from the epidermis and their
      accumulation as immunocompetent dendritic cells in draining lymph nodes. In these
      investigations we have examined the stimulation by allergen of cutaneous TNF
      alpha production and the induced epidermal expression of mRNA for TNF-alpha.
      Topical exposure of mice to oxazolone, a skin-sensitizing chemical, resulted in
      cutaneous TNF-alpha protein production that was maximal 2-h following treatment
      and then declined markedly. The same treatment resulted in highly localized and
      transient expression of epidermal TNF-alpha mRNA as judged by in situ
      hybridization. Epidermal mRNA for TNF-alpha was apparent 10 min following
      exposure to oxazolone, but was no longer detectable at 20 min. A similar pattern
      of TNF-alpha mRNA expression in the epidermis was provoked by intradermal
      exposure to interleukin 1 beta, a cytokine shown previously to induce TNF-alpha.
      Such rigorous regulation of temporal and spatial expression was shown not to be a
      characteristic of all epidermal cytokines induced by chemical allergen. Exposure
      to oxazolone under the same conditions resulted in a more widespread and more
      persistent expression of epidermal mRNA for interleukin 6. These data demonstrate
      that during skin sensitization the induced expression of epidermal TNF-alpha is
      finely controlled in space and time. It is proposed that such regulation
      facilitates the initiation of cutaneous immune responses while preventing
      excessive inflammation that would result from more persistent TNF-alpha
      production.

PMID- 9576068
TI  - Modulation of cartilage proteoglycan metabolism by LIF binding protein.
AB  - Leukaemia inhibitory factor (LIF) and oncostatin M (OSM) exhibit pleiotropic
      biological activities, share many structural and genetic features and bind with
      high affinity to the same receptor (LIF/OSM receptor). A soluble form of the LIF
      R alpha, called LIF binding protein (LBP) has been isolated from mouse serum. LIF
      and OSM stimulate proteoglycan (PG) release and inhibit PG synthesis in cultured
      pig articular cartilage explants. The aim of this study was to determine whether
      LBP can block PG resorption and or reverse the inhibition of PG synthesis induced
      by LIF and OSM. In cultured pig cartilage explants LBP was found to dose
      dependently inhibit LIF stimulated release of PGs and reverse the suppression of
      PG synthesis. LBP was found to substantially attenuate the effects of LIF. In
      contrast only partial inhibition of the stimulatory effect of OSM was observed at
      the highest concentration of LBP available. At maximal concentrations, LBP
      produced minimal reversal of OSM mediated inhibition of PG synthesis. When tested
      in combination LIF and OSM had no additive effects on PG metabolism, but the
      combination of LIF and IL-1 and also OSM and IL-1 did show additive effects in
      respect to stimulation of PG catabolism and inhibition of PG synthesis. These
      effects were significantly greater than those observed for LIF, OSM and IL-1
      alone. The results suggest that pig articular chondrocytes possess the LIF/OSM
      receptor, but possibly not an independent OSM receptor. The actions of mLBP
      indicate that rhLBP could be a clinically useful antagonist for LIF and perhaps
      OSM.

PMID- 9576069
TI  - Contrasting effects of inflammatory cytokines and glucocorticoids on the
      production of activin A in human marrow stromal cells and their implications.
AB  - Human marrow stromal cells were analysed with immunocytochemical staining,
      Northern blot, and functional bioassay for production of activin A. Although
      Northern blot and immunocytochemical staining did not detect the alpha subunit of
      inhibin in human marrow stromal cells, RT-PCR analyses confirmed its presence,
      along with the expected activin beta A PCR products. Present studies showed that
      human marrow fibroblastoid cells were reactive with anti-activin A antibodies and
      that the production of beta A RNA was upregulated by pro-inflammatory
      cytokines/regulators like interleukin 1 alpha (IL-1 alpha), tumour necrosis
      factor-alpha (TNF-alpha), lipopolysaccharide (LPS) or 12-O-tetradecanoylphorbol
      13-acetate (TPA). IL-1 alpha or TNF-alpha stimulated-marrow stromal cells
      accumulated beta A RNA after 2 h of incubation, reaching a peak stimulation at
      approximately 8 h. Biologically active activin A molecules were detected in the
      conditioned media by a bioassay, and their activity was specifically inhibited by
      a blocking antibody or an activin-binding protein, follistatin. Accumulation of
      bioactive activin A in conditioned medium of human marrow stromal cells increased
      after incubation with IL-1 alpha or TNF-alpha. Nuclear run-off assays with TNF
      alpha stimulated marrow stromal cells showed that the enhanced expression of
      activin A was related to an increase in its rate of transcription. In contrast to
      the stimulatory effect of pro-inflammatory cytokines, hydrocortisone and
      dexamethasone at 1 x 10(-7) to 1 x 10(-6) M inhibited both the constitutive and
      the cytokine-stimulated expression of activin beta A RNA, and also the production
      of bioactive activin A protein. The upregulation of activin A production by
      cytokines and its suppression by glucocorticoids imply that activin A may also
      act as a moderator in diverse functions including host defences.

PMID- 9576070
TI  - Effect of age and hormonal state on cytokine synthesis in the monkey.
AB  - The authors studied plasma cytokine activity using cross reactive polyclonal
      antibodies to human cytokines in young and old female monkeys to determine if age
      had any effect on cytokine secretion, and compared hormonal effects as well.
      While interleukin 1 (IL-1) was not higher in aged cycling monkeys, it was after
      menopause. Menopause depressed IL-2 activity also. Variable results were seen
      with the other cytokines.

PMID- 9576071
TI  - A randomized study on eversion versus standard carotid endarterectomy: study
      design and preliminary results: the Everest Trial.
AB  - PURPOSE: The EVEREST Trial was designed to determine whether the surgical
      technique influences the durability and complications of carotid endarterectomy
      (CEA). The current report focuses on the study design and preliminary results.
      METHODS: EVEREST is a randomized multicenter trial. A total of 1353 patients with
      carotid stenosis requiring surgical treatment were randomly assigned to received
      standard (n = 675) or eversion (n = 678) CEA. Primary end points included carotid
      occlusion, major stroke, death, and restenosis rate. RESULTS: The rate of
      perioperative major stroke and death (1.3 for each study group) and the incidence
      of early carotid occlusion (0.6% for eversion vs 0.4% for standard) were similar.
      No significant differences were found between eversion and standard CEA with
      respect to incidence of perioperative transient ischemic accident, minor stroke,
      cranial nerve injuries, neck hematoma, myocardial infarction, or surgical defects
      as detected with intraoperative quality controls. Clamping time was significantly
      shorter for eversion CEA compared with patch standard procedures (31.7 +/- 15.9
      vs 34.5 +/- 14.4 minutes, p = 0.02). A shunt was inserted in 11% of patients
      undergoing eversion CEAs and in 16% of patients undergoing standard procedures.
      Overall 30-day events occurred in 13.3% of the eversion group and in 11.4% of the
      standard group (p = 0.3). At a mean follow-up of 14.9 months (range, 1 to 38
      months), 16 (2.4%) restenoses occurred in the eversion group and 28 (4.1%)
      occurred in the standard group (odds ratio, 0.56; 95% confidence interval, 0.3 to
      1.1; p = 0.08). CONCLUSION: The preliminary results of the EVEREST Trial suggest
      that eversion CEA is a safe and rapid procedure with low major complication
      rates. No significant differences in restenosis rates were observed between
      eversion and standard CEA at the available follow-up. Longer-term results are
      necessary to assess whether the eversion technique influences the durability of
      CEA.

PMID- 9576072
TI  - Clinical consequences of periprosthetic leak after endovascular repair of
      abdominal aortic aneurysm. Endovascular Technologies Investigators.
AB  - PURPOSE: The study was conducted to evaluate risk factors, natural history, and
      clinical consequences of a periprosthetic leak after endovascular repair of an
      abdominal aortic aneurysm. METHODS: We reviewed the initial and follow-up data,
      including angiograms, contrast-enhanced computed tomography (CT) scans, abdominal
      duplex scans, and plain abdominal films for all patients undergoing tube graft
      repair using the endovascular graft system (early prototype) between February 10,
      1993, and January 24, 1995. RESULTS: Sixty-eight patients underwent placement or
      attempted placement of a tube graft implant in 13 centers in the United States.
      Nine patients required conversion to open repair, leaving 59 patients with
      functioning grafts for evaluation. The mean follow-up time was 27 +/- 8 months
      (range, 2 to 48 months). Twenty-eight (47%) of 59 patients had initial
      periprosthetic leaks (6 proximal, 14 distal, 3 proximal and distal, 5
      indeterminate) on their first postoperative CT scans. Fourteen (50%) of the
      initial 28 leaks sealed spontaneously. Two other patients had their leaks sealed
      by endovascular means, leaving 12 patients with persistent leaks for follow-up
      evaluation. Four patients developed late leaks between 18 and 24 months of follow
      up: one who had a spontaneously sealed initial leak, one with a second leak, and
      two who developed late leaks. Of the 16 patients with sealed leaks, 10 had
      aneurysm size reduction during follow-up. Three aneurysm sacs enlarged before
      spontaneous sealing but have not had sufficient follow-up time to document the
      size change since the seal. One patient died of respiratory failure 5 months
      after graft implantation. One patient whose leak was sealed by intervention has
      not yet had a CT scan for evaluation. In one patient with a sealed leak and whose
      aneurysm had initially shrunk, the area reopened and progressed to a nonfatal
      rupture that was surgically corrected. There were two late deaths from unrelated
      causes. Twelve patients in the sealed group are alive and well. Of the 12
      patients with persistent leaks, five underwent open surgical repair without
      complication, and one underwent successful endovascular repair with a second
      graft. Six patients continue to live with their initial grafts and have an
      average aneurysm sac enlargement of 0.1 cm per year. CONCLUSIONS: Although
      initial periprosthetic leaks were common with the use of this early prototype,
      50% spontaneously sealed. The subsequent clinical course of patients with
      persistently sealed leaks was no different from that of patients who had no
      leaks. However, continued CT surveillance is warranted, because in one patient
      with an initially sealed leak, the area reopened and progressed to nonfatal
      rupture. Another two patients without initial leaks developed late leaks. In a
      small group of selected patients with continued leaks, their aneurysms appeared
      to enlarge at a rate considerably slower than would have been expected in
      patients with untreated aneurysm, suggesting that even a person after
      endovascular repair with a persistent leak may have had some beneficial
      hemodynamic modification.

PMID- 9576073
TI  - Use of intravascular ultrasound improves long-term clinical outcome in the
      endovascular management of atherosclerotic aortoiliac occlusive disease.
AB  - PURPOSE: This study was undertaken to determine whether the use of intravascular
      ultrasound (IVUS) during balloon angioplasty and stenting of atherosclerotic
      aortoiliac occlusive lesions improved long-term clinical outcome. IVUS has been
      previously shown to be more accurate than arteriography in evaluating the
      deployment of stents in both peripheral and coronary arteries. Incomplete stent
      deployment has been anecdotally identified as a cause of restenosis or occlusion
      of a treated lesion. To our knowledge, there have been no previous studies that
      demonstrate whether the use of IVUS will affect the long-term patency rate of
      stented arterial lesions. METHODS: Between March 1992 and October 1995, 52
      patients with symptomatic aortoiliac occlusive disease underwent balloon
      angioplasty and stenting of their lesions. We retrospectively reviewed these
      cases to determine whether the use of IVUS influenced the long-term patency rate
      of these interventions. Follow-up ranged from 1 to 4 years with a mean of 28
      months. RESULTS: Fifty-two patients had confirmation of adequate stent deployment
      by arteriography. IVUS was used in conjunction with arteriography in 36 patients
      to evaluate stent deployment. Patients in the IVUS-assisted group were slightly
      younger than those patients who were evaluated solely by arteriography (p <
      0.01). No statistical differences were noted between the two groups with respect
      to coronary artery disease, diabetes mellitus, obstructive pulmonary disease,
      hypertension, or obesity. Length of hospital stay, number of stents used, and
      preoperative ankle brachial indexes were comparable in both groups. In the
      arteriography plus IVUS group, 40% of patients had underdeployed stents by IVUS
      evaluation, though they appeared adequately expanded by arteriography. No
      restenoses or occlusions were seen in the arteriography plus IVUS group.
      Restenosis or occlusion of the stented lesion occurred in 25% of patients
      evaluated by arteriography alone (p < 0.01). These failures were treated by
      either thrombolysis or catheter thrombectomy and were then evaluated with IVUS.
      All were found to have underdeployed stents. Subsequent treatment consisted of
      adequate redeployment of existing stents using IVUS criteria. These salvaged
      reconstructions have continued to remain patent. CONCLUSIONS: The use of IVUS may
      be the best means for assessing adequacy of arterial stent deployment. Our study
      suggests that the use of IVUS improves the long-term clinical outcome of balloon
      angioplasty and stented aortoiliac occlusive lesions.

PMID- 9576074
TI  - Reduced pulsatile wall motion of abdominal aortic aneurysms after endovascular
      repair.
AB  - PURPOSE: The reduced size of abdominal aortic aneurysms (AAAs) after endovascular
      repair suggests lowered intraaneurysmal pressure. In the presence of endoleaks,
      the size is not decreased. Although postoperative intraaneurysmal pressure is
      difficult to record, the pulsatile wall motion (PWM) of aneurysms can be measured
      noninvasively. The aim of this study was to assess the PWM of AAAs before and
      after endovascular repair and to relate the change in the PWM to aneurysmal size
      and presence of endoleaks. METHODS: Forty-seven patients underwent endovascular
      repair of an AAA. The aneurysm diameter and PWM were measured with the use of
      ultrasonic echo-tracking scans preoperatively; at 1, 3, and 6 months; and
      thereafter biannually. Fifteen aneurysms developed endoleaks, whereas 32 were
      completely excluded. The leaks were characterized with the use of computed
      tomographic scanning and angiography. Median follow-up was 12 months
      (interquartile range, 5 to 24 months). RESULTS: The preoperative PWM of the
      aneurysms was 1.0 mm (range, 0.8 to 1.3 mm). After complete endovascular
      exclusion, the PWM was 25% (range, 16% to 37%) of the preoperative value (p <
      0.001), and aneurysm diameter decreased by 8 mm (range, 6 to 14 mm) (p < 0.001).
      After 18 months, no further diameter reduction occurred. In three patients
      without endoleaks but with enlarging aneurysms, the postoperative PWM showed less
      reduction (p < 0.05). Aneurysms with endoleaks showed no diameter decrease, and
      the postoperative PWM was 50% higher than that in the totally excluded cases (p <
      0.01). In five patients with transient endoleaks, the PWM was reduced after
      leakage ceased (p < 0.05). Leaks of various sources displayed similar PWM.
      CONCLUSION: The size and PWM of aneurysms are reduced after endovascular repair.
      The diameter reduction may cease after 1.5 years. Endoleaks are associated with
      higher PWM than expected. Pressure may be transmitted without evidence of leaks.

PMID- 9576075
TI  - Mechanical wall stress in abdominal aortic aneurysm: influence of diameter and
      asymmetry.
AB  - PURPOSE: Risk for rupture of an abdominal aortic aneurysm is widely believed to
      be related to its maximum diameter. From a biomechanical standpoint, however,
      risk is probably more precisely related to mechanical wall stress. Many abdominal
      aortic aneurysms are asymmetric (for example because of anterior bulging with
      posterior expansion limited by the vertebral column). The purpose of this work
      was to investigate the effect of maximum diameter and asymmetric bulge on wall
      stress. METHODS: Three-dimensional computer models of abdominal aortic aneurysms
      were generated. In one protocol, maximum diameter was held constant while bulge
      shape factor was varied. The shape factor took into account the asymmetric shape
      of the bulge. In a second protocol, the shape of the aneurysmal wall was held
      constant while maximum diameter was varied. Wall stress was computed in each
      instance with a commercial software package and assumption of physiologic
      intraluminal pressure. RESULTS: Both maximum diameter and the shape factor were
      found to have substantial influence on the distribution of wall stress within the
      aneurysm. In some instances the maximum stress occurred at the midsection, and in
      others it occurred elsewhere. The magnitude of peak stress acting on the aneurysm
      increased nonlinearly with increasing maximum diameter or increasing asymmetry.
      CONCLUSIONS: Our computer models showed that the stress within the wall of an
      abdominal aortic aneurysm and possibly the potential for rupture are as dependent
      on aneurysm shape as they are on maximum diameter. This information may be
      important in determining severity of individual abdominal aortic aneurysms and in
      improving understanding of the natural history of the disease.

PMID- 9576076
TI  - A ten-year experience of Brescia-Cimino arteriovenous fistula in children:
      technical evolution and refinements.
AB  - PURPOSE: The arteriovenous fistula (AVF) of Brescia-Cimino fulfills nearly all of
      the criteria for an optimal access for chronic hemodialysis, such as long-term
      patency rate, low complication rate, and respect of vascular morphologic
      features. Alternative dialytic methods (i.e., external shunts and vascular
      grafts) cannot easily be applied to pediatric patients, and in addition, these
      methods are responsible for higher complication rates. METHODS: From January 1985
      to December 1994, 112 Brescia-Cimino AVFs were performed in 90 children (average
      age, 5.5 years; range, 5 months to 18 years). The average weight of the children
      was 28 kg (range, 6.5 to 54 kg); 16% of AVFs were performed in children who were
      less than 5 years old, and 18% in children who were less than 15 kg in body
      weight. RESULTS: Chronic renal failure was caused by a nephropathy in 53 cases
      (14 with a nephrotic syndrome), and 37 cases had a uropathy. In all cases a
      phlebography was performed before the microsurgical treatment. Since 1994 an
      inflatable tourniquet has been placed on the selected upper arm because of an
      optimal exsanguination of the operating field. The primary patency rate was
      obtained in all but six of the children; 35% of AVFs had either immediate or late
      complications. Thrombosis was the most frequent complication that we observed. In
      comparison with 79% of late thrombosis, 60% of early thrombosis was cured. Of the
      80 AVFs, 63.5% with a 4-year follow-up are still patent. CONCLUSION: We emphasize
      the following two conclusions: first, microsurgery is essential to create AVFs
      with good results in children as well as in adult patients; and second, the
      results improved after the adoption of an upper-arm exsanguination and ischemia
      (pressure range, 400 mm Hg to 600 mm Hg) that avoided spasm of the vessels with a
      final 35% reduction in surgical time.

PMID- 9576077
TI  - Progressive intermittent claudication is associated with impaired fibrinolysis.
AB  - PURPOSE: Acute complications of atherosclerosis such as stroke and myocardial
      infarction are caused by thrombosis and may be associated with impaired
      fibrinolytic activity. The current study was performed to determine whether
      peripheral arterial disease (PAD) and its progression are also associated with
      impaired fibrinolysis, by measurement of tissue plasminogen activator (tPA, the
      activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1
      (PAI-1). METHODS: The study group consisted of 80 men with a mean age of 69
      years. This included 18 patients with mild intermittent claudication (MC, pain
      free walking distance > or = 200 meters) and 51 patients with severe claudication
      (SC, walking distance <200 meters). Eleven age- and sex-matched patients without
      PAD served as controls. All patients had measurements of serum tPA antigen using
      an enzyme-linked immunoadsorbent assay. Serum levels of tPA and PAI-1 activity
      were assayed with an amidolytic method. Mean +/- SEM levels of the enzyme levels
      in patients with progressively more severe PAD were compared with normal
      controls. RESULTS: Serum PAI-1 activity levels were significantly elevated in
      both PAD groups compared with normal controls (p < 0.02). There were no
      significant differences in the PAI-1 activity levels in groups with worsening
      degrees of PAD. There was a significant decrease in tPA activity levels in
      patients with SC (p = 0.01) relative to those with MC and the normal subjects.
      There was also a significant increase in tPA antigen level in the patients with
      SC compared with those with MC and the control subjects, as well as a significant
      inverse correlation between tPA antigen levels and pain-free walking time in
      patients with claudication (p = 0.001). CONCLUSIONS: All patients with PAD in
      this study had significant reductions in endogenous fibrinolytic activity.
      Patients with SC had more impaired fibrinolytic activity than those with MC and
      the control subjects, suggesting that the progression to more severe levels of
      PAD may be associated with worsening endogenous fibrinolysis.

PMID- 9576078
TI  - Axial transformation of the profunda femoris vein.
AB  - PURPOSE: To highlight a special subset of cases of venous stasis in which the
      profunda femoris vein enlarges to a variable extent (axial transformation) to
      compensate for severe postthrombotic changes in the accompanying superficial
      femoral vein. METHODS: Among 500 consecutively treated patients with severe
      venous stasis, 57 patients had axial transformation of the profunda femoris vein.
      Venous obstruction and reflux were assessed by means of arm-foot pressure
      differential, ambulatory venous pressure measurement, air plethysmography, and
      duplex examination. Ascending and descending venograms also were obtained. A
      variety of valve reconstruction techniques were useful in correcting reflux in
      the enlarged profunda femoris vein and the companion postthrombotic superficial
      femoral vein. RESULTS: In 55% of patients the profunda femoris vein was larger
      than normal and provided partial outflow from the leg through a profunda
      popliteal connection, but the superficial femoral vein was still the dominant
      outflow tract (grades I and II). In 36% of patients the profunda femoris was the
      dominant outflow tract from the leg, and in another 9% it was the sole axial
      outflow tract (grades III and IV). The skin changes of advanced venous stasis
      were present among 92% of patients and frank ulceration among 88%. Antireflux
      operations on the profunda femoris vein and companion superficial femoral vein,
      including ligation and division in some instances, were well tolerated. Despite a
      postthrombotic cause, obstruction did not worsen after surgical treatment, and
      reflux improved according to most laboratory measurements. Complete ulcer healing
      was obtained with the surgical techniques described. The actuarial recurrence
      free survival rates were 90% 1 year and 66% 5 years after treatment. CONCLUSION:
      Axial transformation of the profunda femoris vein is present in a subset of
      instances in which severe postthrombotic changes are present in the companion
      superficial femoral vein. Profunda femoris reflux is invariably present in these
      instances because of compensatory dilatation and enlargement of this vessel.
      Simultaneous valve repair of the axially transformed profunda femoris vein and
      companion superficial femoral vein to abolish reflux yields excellent long-term
      results and healing of stasis ulceration.

PMID- 9576079
TI  - The role of air plethysmography in the diagnosis of chronic venous insufficiency.
AB  - PURPOSE: The role of air plethysmography (APG) in the diagnosis of venous disease
      is not well defined. We conducted this study to investigate the value of APG in
      the diagnosis of chronic venous insufficiency and to determine its correlation
      with the clinical severity of disease and the anatomic distribution of reflux.
      METHODS: We studied 186 lower extremities with duplex scanning and venography and
      measured the venous volume, venous filling index (VFI), ejection fraction, and
      residual volume fraction with APG. Limbs were categorized according to the
      Society for Vascular Surgery and International Society for Cardiovascular Surgery
      classification of clinical severity of disease and according to the anatomic
      distribution of valvular incompetence. RESULTS: Sixty-one limbs had no evidence
      of disease (class 0), 60 limbs had mild disease (classes 1, 2, and 3), and 65
      limbs had severe disease (classes 4, 5, and 6). According to the results of
      duplex scanning and venography, there was no evidence of reflux in 56 limbs.
      Isolated superficial venous reflux occurred in 52 limbs, and perforator reflux,
      alone or in conjunction with superficial reflux, occurred in 30. Deep reflux,
      with or without superficial reflux, was found in 25 limbs. Deep and perforator
      reflux, with or without superficial reflux, was found in 19 limbs. The VFI had a
      sensitivity of 80% and 99% positive predictive value for any type of reflux. The
      VFI was significantly different between groups of limbs with different clinical
      severities of disease or different types of reflux. The incidence of deep or
      perforator reflux in limbs with a normal VFI value was 7%, and it was 82% in
      limbs with a VFI of more than 5. Among 86 limbs with VFI values not corrected
      with use of a thigh tourniquet, 28% did not have evidence of deep or perforator
      reflux, and among 15 limbs with VFI values corrected with the use of a
      tourniquet, 33% had perforator reflux, deep reflux, or both. All APG parameters
      had low positive predictive values for severe disease or ulceration. The ejection
      fraction and residual volume fraction did not influence the clinical severity of
      disease, did not discriminate between types of reflux, and in combination with
      the VFI did not improve the predictive value of APG. CONCLUSIONS: The VFI
      measured by APG is an excellent predictor of venous reflux, provides an estimate
      of the clinical severity of disease, and at high levels predicts deep reflux,
      perforator reflux, or both. Correction of an abnormal VFI with a thigh tourniquet
      is an unreliable predictor of the absence of deep or perforator incompetence. The
      predictive value of APG for severe disease or ulceration is poor. The ejection
      fraction and residual volume fraction, individually or in combination with the
      VFI, add little to the diagnostic value of APG, and their routine performance may
      not be clinically justified.

PMID- 9576080
TI  - Foot venous pressure measurement for evaluation of lower limb venous
      insufficiency.
AB  - PURPOSE: Foot venous pressure measurement is considered to be useful for
      assessing lower limb venous insufficiency, because venous hypertension is the
      main factor predisposing to venous insufficiency. In this study, we investigated
      the utility of foot venous pressure measurement in the evaluation of venous
      insufficiency. METHODS: A total of 148 limbs of 101 patients with venous
      insufficiency associated with varicose veins and treated over 5 years were
      studied. The measurements assessed were percentage decrease in foot venous
      pressure with manual calf compression (%drop), rate of increase in foot venous
      pressure during a 4-second period after release of compression (4SR%), and time
      to 50% recovery of foot venous pressure (RT50). RESULTS: A higher incidence of
      skin changes (clinical, etiologic, anatomic, and pathophysiologic classification
      classes 4 to 6) caused by venous insufficiency was associated with %drop, 4SR%,
      and RT50 values. Skin changes were found in more than 50% of the limbs with a
      %drop less than 50%, 4SR% more than 50%, or RT50 less than 4 seconds. After
      tourniquets were applied to occlude the superficial veins, limbs with severe
      below-knee deep venous reflux (%drop 60.3 +/- 14.6, 4SR% 36.7 +/- 30.2, RT50 13.9
      +/- 14.7) showed significantly worse values than those with no reflux (%drop 79.9
      +/- 3.2, 4SR% 8.1 +/- 3.1, RT50 48.9 +/- 17.9) or with mild above-knee reflux
      (%drop 77.0 +/- 5.0, 4SR% 7.1 +/- 3.2, RT50 46.9 +/- 26.7). After sclerotherapy
      or surgical treatment, including deep venous reconstruction for severe below-knee
      reflux, all limbs showed significant improvement in clinical manifestations and
      foot venous pressure values (%drop 68.1 +/- 7.5 to 76.5 +/- 5.8, 4SR% 33.1 +/-
      12.9 to 12.7 +/- 7.6, RT50 7.5 +/- 4.2 to 20.1 +/- 6.5). CONCLUSION: Foot venous
      pressure measurements showed a good correlation with clinical severity and degree
      of venous reflux and were very useful for evaluating the outcome of therapy for
      venous insufficiency.

PMID- 9576081
TI  - Saphenous vein thrombophlebitis (SVT): a deceptively benign disease.
AB  - PURPOSE: The association between deep vein thrombosis (DVT) and the
      hypercoagulable state is a well-established entity. However, the association
      between saphenous vein thrombophlebitis and coagulation abnormalities has not
      been investigated. Although thrombosis of varicose veins typically runs a benign
      course, phlebitis of the saphenous system may propagate to the deep system or
      saphenofemoral junction that requires more aggressive therapy. Given the
      potential similarity in clinical outcome between saphenous vein thrombophlebitis
      (SVT) and DVT, we have investigated the coagulation profile of patients
      presenting with isolated SVT. METHODS: Seventeen consecutive patients who
      presented to our vascular laboratory with isolated SVT had a coagulation profile
      performed that included antithrombin III (AT III), protein C (PC), protein S (PS)
      antigen and activity levels, activated protein C (APC) resistance, factor V DNA
      mutation, and coagulation factors II and X. All patients had duplex scans
      performed on both the superficial and deep venous systems. Patients with SVT only
      were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and warm soaks as
      outpatients, whereas those patients found to have DVT or a clot at the
      saphenofemoral junction were fully anticoagulated with heparin and coumadin
      therapy. All 17 patients had at least one repeat coagulation profile performed up
      to 5 months after their SVT occurrence to ensure that the results of
      hypercoagulability were not transient. RESULTS: Ten (59%) of the 17 patients with
      SVT had abnormal coagulation profiles on initial presentation. All 10 patients
      who were hypercoagulable had repeat tests and 6 (35%) remained abnormal. Four
      patients who had abnormal results converted to normal values. Seven patients with
      normal coagulation profiles on initial presentation had repeat tests and all
      remained normal. CONCLUSION: The incidence of the hypercoagulable state in
      patients with SVT is high. Thirty-five percent of patients with isolated SVT had
      consistently abnormal coagulation profiles. Patients with SVT may be prone to the
      development of DVT or saphenofemoral junction thrombophlebitis and should be
      closely followed after the initial diagnosis of hypercoagulability.

PMID- 9576082
TI  - In vitro evaluation of multiple arterial stenoses using three-dimensional power
      Doppler angiography.
AB  - PURPOSE: The study was done to improve quantification of multiple arterial
      stenoses and to investigate a new imaging technique for lower limb arteries.
      Three-dimensional power Doppler angiography was used to quantify in vitro
      arterial stenoses. METHODS: We built two types of artery phantoms containing
      multiple stenoses. One used stenotic porcine arteries, and the other was designed
      to control the proximal and distal stenoses while we assessed central stenosis of
      a wall-less agar lumen. Three-dimensional power Doppler angiograms of the flow
      lumens were generated at different flow rates under steady and pulsatile flow
      conditions with a PowerPC 8500 computer-based three-dimensional ultrasound
      imaging system. This experimental system works off-line, performs three
      dimensional acquisition, reconstruction, and display of ultrasound images. Images
      of flow lumens were compared with the measured B-mode images or the true
      geometry. RESULTS: This technique produces good three-dimensional angiographic
      images of the flow lumen, and multiple stenoses do not affect the diagnosis of
      arterial stenoses. With this technique, the average errors for estimating 80% and
      50% area reduction stenoses were -10% and 4%, respectively. CONCLUSIONS: Three
      dimensional power Doppler angiography has the potential to quantitatively grade
      multisegmental stenoses in lower limbs and generate a map for vasculature surgery
      planning.

PMID- 9576083
TI  - Treatment of vascular graft infection by in situ replacement with cryopreserved
      aortic allografts: an experimental study.
AB  - PURPOSE: The purposes of this study were to prove the efficacy of cryopreserved
      aortic allografts to treat an established vascular graft infection by in situ
      replacement in an animal model and to evaluate the role of the antibiotics
      normally used to decontaminate the allografts. METHODS: Twenty-three dogs
      underwent infrarenal aortic replacement with a gelatin-sealed knitted polyester
      graft contaminated in vitro by Staphylococcus epidermidis RP-62. One week later,
      the 18 surviving animals underwent reoperation for graft removal and were
      randomized into three groups for in situ replacement: group I (control, n = 6)
      received a new gelatin-sealed graft; group II (n = 6) received a non-antibiotic
      treated cryopreserved allograft; and group III (n = 6) received an antibiotic
      treated cryopreserved allograft. Control grafts and allografts were removed 4
      weeks after the initial intervention for quantitative bacteriologic analysis and
      histologic analysis. Bacteriologic results were expressed as colony-forming units
      per square centimeter of graft material. Qualitative bacteriologic analysis was
      also obtained from perigraft fluid and tissue. RESULTS: All of the initially
      implanted grafts and all of the control grafts (group I) were infected at the
      time of removal. In group II, three out of six allografts were not totally
      incorporated, whereas in group III incorporation was always complete, with a
      significantly decreased inflammatory reaction. All of the antibiotic-treated
      allografts were sterile, whereas three untreated allografts grew bacteria.
      CONCLUSIONS: In this model, cryopreserved aortic allografts were more resistant
      to reinfection than synthetic grafts after in situ replacement of an infected
      prosthetic graft. However, the antibiotic loading of the cryopreserved aortic
      allograft appears to be essential to obtain optimal therapeutic effects.

PMID- 9576084
TI  - Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular
      endothelial growth factor protects against ischemic vascular occlusion.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a potent stimulator of
      angiogenesis, and transgene expression from adenovirus vectors can provide in
      vivo delivery of proteins. On the basis of this knowledge, we hypothesized that
      local administration of a replication-deficient adenovirus vector expressing
      complementary DNA for VEGF (AdVEGF) would induce collateral vessel formation in
      the setting of ischemia that could protect against subsequent acute vascular
      occlusion. METHODS: Hindlimb ischemia was induced in Sprague-Dawley rats by means
      of unilateral ligation of the common iliac artery immediately followed by
      administration of 4 x 10(9)-plaque-forming units VEGF, the control vector AdNull,
      or phosphate-buffered saline solution into the iliofemoral adipose tissue and
      thigh muscles. Untreated rats with common iliac ligation were used as an
      additional control group. RESULTS: Local VEGF expression was observed for 5 days
      in AdVEGF-treated rats but not in controls. Three weeks after ligation and vector
      administration, the ipsilateral femoral artery was ligated for a model of an
      acute vascular occlusion in the setting of preexisting ischemia. Blood flow to
      the ischemic hindlimb relative to the contralateral hindlimb evaluated with color
      microspheres demonstrated significantly increased blood flow in the AdVEGF
      treated rats compared with each control group (p < 0.0001). Relative blood flow
      assessed by means of 99mTc-sestamibi radionuclide scans also demonstrated
      increased blood flow to the ligated hindlimb of AdVEGF-treated rats compared with
      each control group (p < 0.002). AdVEGF-treated rats also demonstrated increased
      vascularity in the ligated limb compared with each control group as assessed by
      means of angiography (p < 0.0001) and histologic quantification of blood vessels
      less than 80 microm diameter in local adipose tissue and capillaries per muscle
      fiber (p < 0.0002). AdVEGF treatment prevented a rise in femoral venous lactate
      femoral venous concentrations 1 hour after femoral artery ligation in control
      rats (p < 0.04). CONCLUSIONS: An adenovirus vector expressing VEGF complementary
      DNA is capable of stimulating an angiogenic response that protects against acute
      vascular occlusion in the setting of preexisting ischemia, suggesting that in
      vivo gene transfer of VEGF complementary DNA might be useful in prophylaxis of
      advancing arterial occlusive disease.

PMID- 9576085
TI  - Biochemical composition of human peripheral arteries examined with near-infrared
      Raman spectroscopy.
AB  - PURPOSE: Near-infrared Raman spectroscopy provides an important new means of
      analyzing the chemical composition of the arterial wall. The objective of this
      study was to show that Raman spectroscopy can be used to evaluate the lipid and
      calcium salt contents of human peripheral arteries. The results extend a recently
      developed Raman-based method for analyzing the chemical composition of coronary
      arteries. METHODS AND RESULTS: We studied 167 segments of carotid and femoral
      artery wall in various pathologic states. The Raman spectra from these samples
      was accurately modeled. The resulting chemical concentrations were compared with
      the amounts of cholesterol and calcium mineral determined at histologic
      evaluation by an experienced cardiovascular pathologist. Strong correlations
      between spectroscopic measurements and morphologic findings were demonstrated and
      validated the applicability of the method to peripheral arteries. CONCLUSIONS:
      Raman spectroscopy can provide reliable histochemical information about
      peripheral and coronary arteries. Such information may help identify rupture
      prone plaques before the onset of symptoms and allow aggressive and directed
      intervention. Accurate knowledge of the chemical composition of a lesion may be
      useful in selecting the most appropriate treatment.

PMID- 9576086
TI  - Enhancement of heat shock protein expression after transient ischemia in the
      preconditioned spinal cord of rabbits.
AB  - PURPOSE: This investigation was designed to evaluate the mechanism used to
      acquire a tolerance to spinal ischemia. We investigated inductions of the heat
      shock protein (HSP) 70 gene and protein in rabbit spinal cord with or without
      preconditioning. METHODS: Neurologic function, morphologic changes, and
      inductions of HSP70 messenger RNA (mRNA) and protein were compared in the cases
      of a 15-minute ischemia 2 days after sham treatment and a 15-minute ischemia 2
      days after 10-minute preconditioning. RESULT: HSP70 mRNA was induced at 8 hours
      of reperfusion after a 15-minute ischemia 2 days after sham treatment. HSP70
      protein was induced slightly in selective motor neuron cells at 8 hours of
      reperfusion, and about 70% of motor neuron cells showed selective cell death
      after 7 days of reperfusion (p < 0.01). On the other hand, large populations of
      the motor neuron cells survived at 7 days after the 15-minute ischemia that was
      applied at 2 days after preconditioning (p < 0.01). HSP70 mRNA was induced
      persistently as compared with the case of a 15-minute ischemia 2 days after sham
      treatment. The motor neuron cells strongly produced immunoreactive HSP70 from 8
      hours to 2 days. CONCLUSION: Preconditioning with 10-minute ischemia enhanced and
      prolonged the HSP70 gene expression at both mRNA and protein levels and saved the
      motor neuron cells from subsequent lethal ischemia. These changes of HSP70 gene
      expression may play an important role in the acquisition of ischemic tolerance of
      motor neuron cells in rabbit spinal cord.

PMID- 9576087
TI  - Direct in vivo measurement of flow-dependent nitric oxide production in
      mesenteric resistance arteries.
AB  - PURPOSE: To determine whether the concentration of nitric oxide (NO) at the
      arterial wall is increased subsequent to the abrupt elevation of blood flow in
      resistance arteries. METHODS: Eight dogs underwent laparotomy with anesthesia,
      and their small bowels were exteriorized. NO concentration was measured with NO
      specific electrodes (200-micro-tip diameter) at the outer wall of the mesenteric
      arteries. Flow was increased by occlusion of the adjacent mesenteric arteries. In
      four animals, flow and NO concentration were measured after the administration of
      Nomega-nitro-L-arginine-methyl ester (L-NAME) to inhibit NO production. RESULTS:
      As arterial flow was increased from a baseline of 5.4 +/- 1.3 ml/min to 10.9 +/-
      1.8 ml/min (p = 0.001), NO electrode current was elevated in every animal. With
      repetition of the flow stimulus, the response tended to be attenuated. In the
      first experimental trial, NO electrode current measured at the arterial wall
      increased from 2.86 +/- 0.56 to 3.00 +/- 0.60 nA (p = 0.02). L-NAME (10 mg/kg
      intravenous) effectively inhibited NO synthase as indicated by the elevation of
      mean arterial pressure (11 +/- 1.7 mm Hg; p = 0.04). After administration of L
      NAME, NO electrode current measured at the outer arterial wall fell 0.23 +/- 0.05
      nA (p = 0.02). CONCLUSIONS: The data indicate that a doubling of blood flow in
      the canine mesenteric resistance arteries is associated with an increase in NO
      concentration of at least 100 nm at the outer arterial wall. This association is
      probably a substantial underestimation of the actual concentration because of the
      geometry of the electrode tip. To our knowledge, ours is the first report of
      direct in vivo measurement of flow-dependent NO release in resistance arteries.

PMID- 9576088
TI  - Evidence of apoptosis in human carotid atheroma.
AB  - PURPOSE: Apoptosis is a morphologically distinct form of programmed cell death
      that plays a major role in cellular development and homeostasis. In this study,
      we examined the role that apoptosis may have in the pathogenesis of
      atherosclerosis. METHODS: We examined immunohistochemically 20 normal carotid
      arteries and the carotid arteries of 86 patients (mean age, 68 years; range, 52
      to 80 years) who underwent atherectomy for primary atherosclerosis. The
      expression of two genes, BCL2, which inhibits apoptosis, and BAX, which induces
      apoptosis, was examined and correlated to the presence of risk factors that
      included hypertension, smoking, hyperlipidemia, and diabetes mellitus. RESULTS:
      BAX expression was found in 26 of 86 cases (30%), and no immunoreactivity was
      found in the normal carotid specimens. BCL2 expression was not seen in any
      examined tissues (atherosclerotic or normal carotid arteries). Of the 26 patients
      who expressed the BAX gene, 22 were hypertensive (85%), and hypertension (>160/95
      mm Hg) was present in 25 of 60 patients (41%) who did not express the BAX gene (p
      < 0.01). No significant correlation was found between the expression of the BAX
      gene and other risk factors (smoking, hyperlipidemia, diabetes mellitus) or
      presenting symptoms. CONCLUSIONS: In a significant number of stenosed carotid
      arteries (30%), we found no evidence of apoptosis suggested by the presence of
      BAX expression. Hypertension was more prevalent in those patients with BAX gene
      expression than in those patients without BAX gene expression. BCL2 expression,
      which inhibits apoptosis, was not found. Further study of this phenomenon may
      contribute to the discovery of new treatments for atherosclerosis.

PMID- 9576090
TI  - Mesenteric shunting decreases visceral ischemia during thoracoabdominal aneurysm
      repair.
AB  - PURPOSE: A technique to decrease visceral ischemic time during thoracoabdominal
      aneurysm (TAA) repair is reported. METHODS: A 10 mm Dacron side-arm graft is
      attached to the aortic prosthesis and positioned immediately distal to the
      planned proximal thoracic aortic anastomosis. On completion of the anastomosis, a
      16 to 22 Fr perfusion catheter is attached to the side-arm graft and inserted
      into the orifice of the celiac axis or superior mesenteric artery. The cross
      clamp is then placed on the aortic graft distal to the mesenteric side-arm graft.
      Pulsatile arterial perfusion is thus established to the visceral circulation
      while intercostal anastomoses or reconstruction of celiac, superior mesenteric,
      and right renal arteries is performed. Visceral ischemic time and the rise in end
      tidal Pco2 after reconstruction of the visceral vessels in patients with
      mesenteric shunting was compared with a control group matched for aneurysm extent
      and treated immediately before use of the mesenteric shunt technique. RESULTS:
      Between July and Oct, 1996, the technique was applied in 15 patients undergoing
      type I, II, or III TAA repair with a clamp and sew technique. The mean decrease
      in systolic arterial pressure was 12.5 +/- 8.5 mm Hg, with a concomitant rise in
      end-tidal Pco2 (mean, 6.9 +/- 5.8 mm Hg), after perfusion was established through
      the mesenteric shunt. Mean time to establishment of visceral perfusion through
      the shunt was 25.5 +/- 4.4 minutes; the resultant decrement in visceral ischemic
      time averaged 31.3 minutes (i.e., until celiac, superior mesenteric, and right
      renal arteries were reconstructed). Compared with controls, patients with shunts
      had a significantly decreased (6.9 +/- 5.8 versus 21.6 +/- 8.4 mm Hg; p = 0.0003)
      rise in end-tidal CO2 on completion of visceral vessel reconstruction.
      CONCLUSIONS: In-line mesenteric shunting is a simple method to decrease visceral
      ischemia during TAA repair, and it is adaptable to clamp and sew or partial
      bypass and distal perfusion operative techniques.

PMID- 9576089
TI  - Surgical treatment for transvenous tumor extension into the heart: four cases.
AB  - From 1984 to 1996, four patients with transvenous intracardiac tumor extension
      underwent operations in the Kobe University Hospital. The primary tumors of two
      were intravenous leiomyomatoses originating from the uterus; a third patient had
      invasive thymoma, and the fourth patient had clear cell sarcoma of the kidney. In
      1985, one patient had a curative, staged resection. One-stage operations were
      carried out in three patients, and all intracardiac tumors were successfully
      resected en bloc with the primary tumors under conditions of electrical
      ventricular fibrillation and mild hypothermia. Combined venous reconstructions
      were necessary for en bloc resection in three cases. Two patients with malignancy
      received postoperative chemoradiotherapy, and all four patients were discharged
      uneventfully from our hospital. We consider radical resection with curative
      intent only for patients with tumors extending into the heart. In these cases, a
      one-stage operation is preferable, and electrical ventricular fibrillation with
      mild hypothermia is a recommended method of circulatory assist because of its
      simplicity.

PMID- 9576092
TI  - A late complication of internal carotid artery stenting.
AB  - Carotid angioplasty and stenting is gaining in popularity as an alternative to
      carotid endarterectomy for the treatment of symptomatic critical stenoses of the
      internal carotid artery. However, the durability of this technique and the
      incidence of recurrent stenoses has not yet been fully evaluated. It has been
      reported that mechanical factors may cause deformity of a Palmaz stent, negating
      the initial benefits of the procedure. We describe successful carotid
      endarterectomy after distortion of a Strecker balloon-expandable stent.

PMID- 9576091
TI  - Evoked thrill: a simple intraoperative maneuver predicts early patency of
      arteriovenous fistulas.

PMID- 9576093
TI  - Percutaneous stenting for symptomatic stenosis of aberrant right subclavian
      artery.
AB  - Aberrant origin of the right subclavian artery is the most common abnormality of
      the aortic arch vessels and occurs in approximately 0.5% to 1% of the population.
      Symptoms can result from compression of the esophagus by the aberrant vessel,
      aneurysm formation, or atherosclerotic occlusion. Occlusive symptoms are
      typically relieved by surgical revascularization (i.e., transposition or carotid
      subclavian bypass) through a cervical approach. An alternative approach to the
      management of stenosis of normal subclavian arteries is percutaneous angioplasty
      and stenting, an approach not previously used for occlusive disease of an
      aberrant right subclavian artery. We describe a case of focal stenosis of an
      aberrant right subclavian artery causing dizziness and arm claudication in a
      patient who underwent successful percutaneous angioplasty and stenting.

PMID- 9576094
TI  - Restoration of the pelvic circulation in patients with abdominal aortic aneurysms
      receiving aortobifemoral grafts.
AB  - When operating on abdominal aortic aneurysms associated with stenoses or
      occlusions of iliac vessels, surgeons may face the problem of reestablishing
      circulation to pelvic or gluteal territories. A new technique consists of
      anastomosing a posterior opening in the body or one of the branches of a
      bifurcated graft, distally sutured to the femoral artery, to the distal aortic
      stump, which contains all the patent vessels arising from the end of the aorta,
      such as inferior mesenteric and lumbar arteries. This technique, successfully
      performed in two cases, has the advantages of avoiding closure of the distal
      aortic stump and a possible backflow leak and of ensuring adequate pelvic
      circulation.

PMID- 9576095
TI  - A serpentine and hypoplastic infrarenal aorta associated with aneurysm: a case
      report.

PMID- 9576096
TI  - Preaortic iliac confluence: a rare anomaly of the inferior vena cava.

PMID- 9576097
TI  - Aortic stump closure with a titanium permanent clamp: a useful emergency method.
AB  - Successful aortic stump closure in a patient with Behcet's disease was
      accomplished with a permanent titanium clamp. In May 1990, a saccular infrarenal
      abdominal aortic aneurysm was detected in this patient, and prosthetic graft
      replacement was carried out. One year later, this graft was removed because of
      perigraft fluid collection; the aortic stump was sutured closed, and a right
      axillobifemoral bypass was done. In November 1994, the patient was admitted to
      the hospital because of an aortoenteric fistula. An emergency operation was
      performed, and the aortic stump was managed successfully with a permanent clamp.
      In patients with Behcet's disease, use of a permanent clamp may offer an
      alternative to traditional methods for closing blown-out aortic stumps.

PMID- 9576098
TI  - Self-limited spontaneous dissection of the main trunk of the superior mesenteric
      artery.
AB  - Spontaneous dissection of the splanchnic arteries is rare and reportedly carries
      a high risk of mortality. Two cases with spontaneous dissection of the main trunk
      of the superior mesenteric artery followed by a self-limited clinical course are
      presented. Current management strategies, including bypass operation, patch
      angioplasty, and conservative treatments, are discussed. Emphasis is placed on
      the role of nonsurgical management with careful follow-up with the use of new
      technologies such as duplex and computed tomography scanning.

PMID- 9576099
TI  - Cystic, myxomatous adventitial degeneration of a saphenous vein.
AB  - We describe the case of a 75-year-old woman with adventitial cystic degeneration
      of the great saphenous vein. Involvement of the great saphenous vein has been
      unreported previously. Intravenous cysts containing mucinous material were found
      in the great saphenous vein. Histopathologic examination revealed mucus-filled
      cysts in the adventitia of the vein, and myxomatous degeneration of the
      adventitial connective tissue was found.

PMID- 9576101
TI  - Scientific evidence demonstrating the safety of carotid angioplasty and stenting:
      do we have enough to draw conclusions yet?

PMID- 9576100
TI  - Ruptured popliteal artery aneurysm.
AB  - Popliteal artery aneurysms rarely rupture. We treated a 91-year-old man who
      presented with a deep venous thrombosis and anemia; rupture of a popliteal artery
      aneurysm was suspected only after compartment syndrome isolated to the thigh
      developed as the result of bleeding. Although fasciotomy was required on the
      basis of the clinical examination alone, the cause of the problem, operative
      strategy, and definitive treatment (i.e., resection and bypass) were clarified by
      the preoperative computed tomography scan. Ruptured popliteal aneurysm can
      manifest as a massively swollen leg with anemia and should be suspected if no
      other cause is evident.

PMID- 9576102
TI  - Status of carotid angioplasty and stenting trials.

PMID- 9576103
TI  - Timing is everything in life: conditional transgene expression in the
      cardiovascular system.
AB  - Manipulation of the mouse genome by traditional transgenic approaches has
      facilitated studies of gene function within the context of the intact organism
      and allowed for the creation of useful animal models of human disease. However,
      the timing of gene activation or repression is a critical determinant of
      phenotype, and the ability to regulate the temporal profile of transgene
      expression remains an important experimental goal. In this Mini Review, we
      describe the current status of systems to tightly regulate target gene expression
      in vivo, focusing on binary systems using chimeric transcription factors.
      Although experimental difficulties persist, regulated expression systems are
      beginning to produce conditional phenotypes with exciting experimental
      implications. We review the experience to date and examine the potential utility
      of these approaches within the context of cardiovascular medicine.

PMID- 9576106
TI  - Overexpression of human endothelial nitric oxide synthase in rat vascular smooth
      muscle cells and in balloon-injured carotid artery.
AB  - Endothelial cells in normal blood vessels might prevent the unscheduled
      proliferation of smooth muscle cells (SMCs) by the expression of cell migration
      and growth inhibitors. NO, a potent vasodilator, generated by endothelium
      specific constitutive NO synthase (ecNOS) might be such an inhibitor. To test
      this hypothesis, we overexpressed human ecNOS in syngeneic rat arterial SMCs
      using retrovirus-mediated gene transfer. Compared with SMCs transduced with
      vector alone (LXSN SMCs), DNA synthesis and cell proliferation were inhibited in
      the ecNOS-expressing SMCs (LCNSN SMCs). Basal and stimulated (by the calcium
      ionophore A23187) secretion of NO and intracellular cGMP were increased in LCNSN
      SMCs. Nomega-Nitro-L-arginine (L-NA), an inhibitor of NO synthesis, enhanced the
      proliferation of LCNSN SMCs but had no effect on LXSN SMCs. LCNSN SMCs seeded
      onto the luminal surface of balloon-injured rat carotid arteries inhibited
      neointimal formation by 37% and induced marked dilatation (3-fold increase in
      vessel diameter) at 2 weeks compared with LXSN SMC-seeded arteries. Orally
      administered L-NA blocked these changes. Phosphorylation of vasodilator
      stimulated phosphoprotein, which is regulated in part by NO, was elevated in
      LCNSN SMCs and in LCNSN SMC-seeded arteries. This study demonstrates that NO
      generation by ecNOS inhibits SMC proliferation in vitro and modulates vascular
      tone locally in vivo.

PMID- 9576104
TI  - Thy-1, a novel marker for angiogenesis upregulated by inflammatory cytokines.
AB  - We identified the cell surface glycoprotein Thy-1 on the endothelium of newly
      formed blood vessels in four models of angiogenesis in adult rats. Anti-Thy-1
      staining showed that Thy-1 was upregulated in adventitial blood vessels after
      balloon injury to the carotid artery. Preabsorption with a rat Thy-1-Ig fusion
      construct eliminated all immunoreactivity and thus confirmed the specificity of
      the Thy-1 staining. Thy-1 was also expressed in the endothelium of small blood
      vessels formed after tumor implantation in the cornea, in periureteral vessels
      formed after ligation of the renal artery, and in small blood vessels of the
      uterus formed during pregnancy. In contrast with its expression during adult
      angiogenesis, Thy-1 was not expressed in the endothelium of blood vessels during
      embryonic angiogenesis. In vitro, the inflammatory cytokines interleukin-1beta
      and tumor necrosis factor-alpha upregulated Thy-1 mRNA by 8- and 14-fold,
      respectively. Vascular endothelial growth factor, basic fibroblast growth factor,
      transforming growth factor-beta, and platelet-derived growth factor-BB had no
      effect on Thy-1 mRNA. Thus, Thy-1 appears to be a marker of adult but not
      embryonic angiogenesis. The upregulation of Thy-1 by cytokines but not growth
      factors indicates the importance of inflammation in the pathogenesis of adult
      angiogenesis.

PMID- 9576105
TI  - Synergistic inhibition of vascular smooth muscle cell migration by
      phosphodiesterase 3 and phosphodiesterase 4 inhibitors.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) hydrolyze cAMP or cGMP and terminate
      their signaling. Two important families of PDEs that regulate cAMP signaling in
      cardiovascular tissues are the cGMP-inhibited PDEs (PDE3) and the cAMP-specific
      PDEs (PDE4). In this study, we have used a combination of an in vitro motility
      assay and a sensitive method for the measurement of cAMP in order to determine
      the relative roles of PDE3 and of PDE4 in the regulation of cAMP-mediated
      inhibition of VSMC migration. Our data demonstrate that forskolin, an activator
      of adenylyl cyclases, causes concentration-dependent inhibition of platelet
      derived growth factor-induced VSMC migration. Incubation of cultured VSMCs with a
      PDE4-selective inhibitor, Ro 20-1724, markedly potentiated both the antimigratory
      effect and the increase in cAMP caused by forskolin. Cilostamide, a PDE3
      selective compound, did not affect either the antimigratory activity of forskolin
      or its ability to increase cAMP. Cilostamide and Ro 20-1724 interacted
      synergistically to potentiate the inhibition of VSMC migration by forskolin and
      caused a supra-additive increase in cAMP. These data are consistent with an
      important role for both PDE3 and PDE4 in the regulation of cAMP-mediated
      inhibition of VSMC migration.

PMID- 9576107
TI  - Protection of the arterial internal elastic lamina by inhibition of the renin
      angiotensin system in the rat.
AB  - Spontaneous rupture of the internal elastic lamina (IEL) occurs in some arteries
      of the rat during growth and aging. Inbred, normotensive, Brown Norway (BN) rats
      are particularly susceptible to rupture of the IEL, especially in the abdominal
      aorta (AA). Preliminary experiments showed that different angiotensin-converting
      enzyme (ACE) inhibitors protect against rupture of the IEL in the BN rat to a
      greater extent than hydralazine, suggesting a role of the renin-angiotensin
      system (RAS) in this phenomenon. To explore this possibility, we have treated
      male BN rats from 4.5 to 14 weeks of age with either enalapril or losartan (both
      at 1, 3, and 10 mg x kg(-1) x d(-1)) or with the calcium antagonists mibefradil
      (at 3, 10, 30, and 45 mg x kg(-1) x d(-1)) and amlodipine (at 30 mg x kg(-1) x d(
      1)). Systolic blood pressure (SBP) was measured weekly, and at the end of
      treatment we (1) recorded body and heart weights, (2) measured various parameters
      of the RAS in plasma, (3) quantified interruptions in the IEL on "en face"
      preparations of AA, and (4) quantified elastin, collagen, and cell proteins in
      the media of the thoracic aorta. Results showed that enalapril and losartan
      similarly decrease SBP and rupture of the IEL in the AA, suggesting that
      enalapril inhibits the latter via a decrease in the production of angiotensin II
      (Ang II) and not via another effect on ACE. The decrease in IEL rupture and in
      SBP, as well as the modifications in the parameters of the RAS, were all dose
      dependent. Mibefradil had little effect on the RAS and, at the highest doses,
      decreased SBP to an extent similar to that for enalapril at 3 mg x kg(-1) x d(-1)
      but did not significantly inhibit IEL rupture. Amlodipine decreased SBP,
      increased plasma renin concentration, and was without effect on IEL rupture. All
      treatments at the highest doses had a hypotrophic effect on the aortic media but
      differed in their effects on the heart, with enalapril and losartan decreasing
      and mibefradil and amlodipine increasing heart weight, suggesting that the
      inhibition of IEL rupture may be related to a cardiac hypotrophic effect. All
      these results, taken together, suggest that Ang II plays a role in the rupture of
      the IEL that is, in part, independent of SBP.

PMID- 9576108
TI  - Inhibition of rat cardiac muscle contraction and mitochondrial respiration by
      endogenous peroxynitrite formation during posthypoxic reoxygenation.
AB  - This study was designed to investigate the potential role of endogenous
      peroxynitrite (ONOO-) formation in the inhibition of cardiac muscle contractility
      and mitochondrial respiration during posthypoxic reoxygenation. Isometric
      contraction of isolated rat left ventricular posterior papillary muscle was
      virtually eliminated at the end of an exposure to 15 minutes of hypoxia and
      remained 40+/-5% depressed an hour after the reintroduction of O2. O2 uptake by
      rat left ventricular cardiac muscle, measured by a Clark-type O2 electrode, was
      also inhibited by 24+/-2% at 10 minutes after reoxygenation. The inhibition of
      contractility and respiration during posthypoxic reoxygenation was markedly
      attenuated by the NO synthase inhibitor nitro-L-arginine, exogenous superoxide
      dismutase, and the ONOO- scavenger urate but not by the hydroxyl radical
      scavenger mannitol. Generation of ONOO- with the NO donor S-nitroso-N
      acetylpenicillamine (SNAP) plus the superoxide-releasing agent pyrogallol caused
      an irreversible inhibition of cardiac contractile and respiratory function.
      Unlike ONOO-, exogenous (SNAP) and endogenous (bradykinin) sources of NO
      inhibited contractility in a reversible manner. Under conditions of comparable
      amounts of respiratory inhibition in unstimulated incubated muscle, the NO
      dependent agents and the mitochondrial antagonist NaCN produced a smaller degree
      of suppression of contractility compared with ONOO- and posthypoxic
      reoxygenation. These results are consistent with a contributing role for
      endogenous ONOO- formation in the inhibition of cardiac muscle contractility and
      mitochondrial respiration during posthypoxic reoxygenation.

PMID- 9576109
TI  - Impaired cardiac energetics in mice lacking muscle-specific isoenzymes of
      creatine kinase.
AB  - Our purpose was to determine whether hearts from mice bioengineered to lack
      either the M isoform of creatine kinase (MCK-/- mice) or both the M and
      mitochondrial isoforms (M/MtCK-/- mice) have deficits in cardiac contractile
      function and energetics, which have previously been reported in skeletal muscle
      from these mice. The phenotype of hearts with deleted creatine kinase (CK) genes
      is of clinical interest, since heart failure is associated with decreased total
      CK activity and changes in the relative amounts of the CK isoforms in the heart.
      We measured isovolumic contractile performance in isolated perfused hearts from
      wild-type, MCK-/-, and M/MtCK-/- mice simultaneously with cardiac energetics (31P
      nuclear magnetic resonance spectroscopy) at baseline, during increased cardiac
      work, and during recovery. Hearts from wild-type, MCK-/-, and M/MtCK-/- mice had
      comparable baseline function and responded to 10 minutes of increased heart rate
      and perfusate Ca2+ with similar increases in rate-pressure product (48+/-5%, 42+/
      6%, and 51+/-6%, respectively). Despite a similar contractile response, M/MtCK-/-
      hearts increased [ADP] by 95%, whereas wild-type and MCK-/- hearts maintained
      [ADP] at baseline levels. The free energy released from ATP hydrolysis decreased
      by 3.6 kJ/mol in M/MtCK-/- hearts during increased cardiac work but only slightly
      in wild-type (1.7 kJ/mol) and MCK-/- (1.5 kJ/mol) hearts. In contrast to what has
      been reported in skeletal muscle, M/MtCK-/- hearts were able to hydrolyze and
      resynthesize phosphocreatine. Taken together, our results demonstrate that when
      CK activity is lowered below a certain level, increases in cardiac work become
      more "energetically costly" in terms of high-energy phosphate use, accumulation
      of ADP, and decreases in free energy released from ATP hydrolysis, but not in
      terms of myocardial oxygen consumption.

PMID- 9576110
TI  - Smooth muscle-specific expression of the smooth muscle myosin heavy chain gene in
      transgenic mice requires 5'-flanking and first intronic DNA sequence.
AB  - The smooth muscle myosin heavy chain (SM-MHC) gene encodes a major contractile
      protein whose expression exclusively marks the smooth muscle cell (SMC) lineage.
      To better understand smooth muscle differentiation at the transcriptional level,
      we have initiated studies to identify those DNA sequences critical for expression
      of the SM-MHC gene. Here we report the identification of an SM-MHC promoter
      intronic DNA fragment that directs smooth muscle-specific expression in
      transgenic mice. Transgenic mice harboring an SM-MHC-lacZ reporter construct
      containing approximately 16 kb of the SM-MHC genomic region from -4.2 to + 11.6
      kb (within the first intron) expressed the lacZ transgene in all smooth muscle
      tissue types. The inclusion of the intronic sequence was required for transgene
      expression, since 4.2 kb of the 5'-flanking region alone was not sufficient for
      expression. In the adult mouse, transgene expression was observed in both
      arterial and venous smooth muscle, in airway smooth muscle of the trachea and
      bronchi, and in the smooth muscle layers of all abdominal organs, including the
      stomach, intestine, ureters, and bladder. During development, transgene
      expression was first detected in airway SMCs at embryonic day 12.5 and in
      vascular and visceral SMC tissues by embryonic day 14.5. Of interest, expression
      of the SM-MHC transgene was markedly reduced or absent in some SMC tissues,
      including the pulmonary circulation. Moreover, the transgene exhibited a
      heterogeneous pattern between individual SMCs within a given tissue, suggesting
      the possibility of the existence of different SM-MHC gene regulatory programs
      between SMC subpopulations and/or of episodic rather than continuous expression
      of the SM-MHC gene. To our knowledge, results of these studies are the first to
      identify a promoter region that confers complete SMC specificity in vivo, thus
      providing a system with which to define SMC-specific transcriptional regulatory
      mechanisms and to design vectors for SMC-specific gene targeting.

PMID- 9576111
TI  - Virtual electrode-induced phase singularity: a basic mechanism of defibrillation
      failure.
AB  - Delivery of a strong electric shock to the heart remains the only effective
      therapy against ventricular fibrillation. Despite significant improvements in
      implantable cardioverter defibrillator (ICD) therapy, the fundamental mechanisms
      of defibrillation remain poorly understood. We have recently demonstrated that a
      monophasic defibrillation shock produces a highly nonuniform epicardial
      polarization pattern, referred to as a virtual electrode pattern (VEP). The VEP
      consists of large adjacent areas of strong positive and negative polarization. We
      sought to determine whether the VEP may be responsible for defibrillation failure
      by creating dispersion of postshock repolarization and reentry. Truncated
      exponential biphasic and monophasic shocks were delivered from a bipolar ICD lead
      in Langendorff-perfused rabbit hearts. Epicardial electrical activity was mapped
      during and after defibrillation shocks and shocks applied at the plateau phase of
      a normal action potential produced by ventricular pacing. A high-resolution
      fluorescence mapping system with 256 recording sites and a voltage-sensitive dye
      were used. Biphasic shocks with a weak second phase (<20% leading-edge voltage of
      the second phase with respect to the leading-edge voltage of the first phase)
      produced VEPs similar to monophasic shocks. Biphasic shocks with a strong second
      phase (>70%) produced VEPs of reversed polarity. Both of these waveforms resulted
      in extra beats and arrhythmias. However, biphasic waveforms with intermediate
      second-phase voltages (20% to 70% of first-phase voltage) produced no VEP,
      because of an asymmetric reversal of the first-phase polarization. Therefore,
      there was no substrate for postshock dispersion of repolarization. Shocks
      producing strong VEPs resulted in postshock reentrant arrhythmias via a mechanism
      of phase singularity. Points of phase singularity were created by the shock in
      the intersection of areas of positive, negative, and no polarization, which were
      set by the shock to excited, excitable, and refractory states, respectively.
      Shock-induced VEPs may reinduce arrhythmias via a phase-singularity mechanism.
      Strong shocks may overcome the preshock electrical activity and create phase
      singularities, regardless of the preshock phase distribution. Optimal
      defibrillation waveforms did not produce VEPs because of an asymmetric effect of
      phase reversal on membrane polarization.

PMID- 9576112
TI  - Angiogenesis is coming of age.

PMID- 9576113
TI  - Review of alterations in endothelial nitric oxide production in diabetes:
      protective role of arginine on endothelial dysfunction.

PMID- 9576114
TI  - Role of nitric oxide in adenosine-induced vasodilation in humans.
AB  - Vasodilation is one of the most prominent effects of adenosine and one of the
      first to be recognized, but its mechanism of action is not completely understood.
      In particular, there is conflicting information about the potential contribution
      of endothelial factors. The purpose of this study was to explore the role of
      nitric oxide in the vasodilatory effect of adenosine. Forearm blood flow
      responses to intrabrachial adenosine infusion (125 microg/min) were assessed with
      venous occlusion plethysmography during intrabrachial infusion of saline or the
      nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (12.5 mg/min).
      Intrabrachial infusions of acetylcholine (50 microg/min) and nitroprusside (3
      microg/min) were used as a positive and negative control, respectively. These
      doses were chosen to produce comparable levels of vasodilation. In a separate
      study, a second saline infusion was administered instead of L-NMMA to rule out
      time-related effects. As expected, pretreatment with L-NMMA reduced acetylcholine
      induced vasodilation; 50 microg/min acetylcholine increased forearm blood flow by
      150+/-43% and 51+/-12% during saline and L-NMMA infusion, respectively (P<.01,
      n=6). In contrast, L-NMMA did not affect the increase in forearm blood flow
      produced by 3 microg/min nitroprusside (165+/-30% and 248+/-41% during saline and
      L-NMMA, respectively) or adenosine (173+/-48% and 270+/-75% during saline and L
      NMMA, respectively). On the basis of our observations, we conclude that adenosine
      induced vasodilation is not mediated by nitric oxide in the human forearm.

PMID- 9576115
TI  - Enhanced vascular reactivity during inhibition of nitric oxide synthesis in
      pregnant rats.
AB  - Pregnancy-induced hypertension has been suggested to be mediated by several
      mechanisms, including reduced nitric oxide (NO) synthesis. In this study, the
      effects of chronic treatment with the NO synthase inhibitor NG-nitro-L-arginine
      methyl ester (L-NAME) on blood pressure and the underlying changes in vascular
      reactivity were investigated in virgin and late-pregnancy Sprague-Dawley rats.
      The systolic blood pressure was 120+/-2, 124+/-5, 116+/-4, and 171+/-5 mm Hg in
      untreated virgin, virgin treated with L-NAME, untreated pregnant, and pregnant
      treated with L-NAME rats, respectively. The rats were killed, and the thoracic
      aorta was cut into strips for measurement of active stress in response to alpha1
      adrenergic stimulation with phenylephrine and membrane depolarization by high
      KCl. In pregnant rats, the maximal active stress to phenylephrine (0.31+/-0.03 x
      10(4) N/m2) and the high-KCl-induced active stress (0.55+/-0.09 x 10(4) N/m2)
      were smaller than those in virgin rats. By contrast, in the L-NAME-treated
      pregnant rats, the maximal phenylephrine-induced active stress (0.76+/-0.1 x
      10(4) N/m2) was greater than that in virgin rats (0.52+/-0.1 x 10(4) N/m2),
      whereas the high-KCl-induced active stress (1.08+/-0.14 x 10(4) N/m2) was
      indistinguishable from that in virgin rats (1.03+/-0.14 x 10(4) N/m2). Treatment
      with L-NAME did not affect the phenylephrine-releasable Ca2+ stores in pregnant
      rats and had minimal effect on active stress in virgin rats. Thus, reduction of
      NO synthesis during late pregnancy is associated with a significant increase in
      blood pressure and vascular responsiveness to alpha-adrenergic stimulation, which
      can possibly be explained in part by enhanced Ca2+ entry from extracellular
      space. However, other mechanisms such as increased myofilament force sensitivity
      to Ca2+ and/or activation of a completely Ca2+-independent mechanism cannot be
      excluded.

PMID- 9576116
TI  - Hypertensive vascular disease as a cause of death in blacks versus whites:
      autopsy findings in 587 adults.
AB  - Cardiovascular disease is the major cause of excess mortality among urban US
      blacks, but autopsy data comparing black-white differences in underlying
      pathological causes of cardiovascular death are lacking. We reviewed all 720
      adult cases autopsied in 1991 in the New York City Medical Examiner's Office in
      which the coded cause of death was cardiovascular disease (International
      Classification of Diseases, 9th Revision, codes 391, 393 to 398, 401 to 404, 410,
      411, 414 to 417, 420 to 438, and 440 to 444). After exclusion of 133 cases
      because race was missing or coded as other than black or white, gender was not
      coded, or there was an unusual circumstances of death or extreme obesity, 587
      cases were available for analysis. There were 314 black and 273 white subjects.
      Black women were younger than white women at time of death (mean age, 54.7 versus
      61.5 years; P<.001), whereas black and white men did not differ in mean age at
      death. Hypertensive vascular disease was the autopsy cause of death in 42% of
      blacks compared with 23% of whites (P<.001). Conversely, atherosclerotic heart
      disease was the autopsy cause of death in 64% of white subjects but only 38% of
      blacks. These patterns were consistent in both sexes and after adjustment for
      age. Hypertensive vascular disease was far more common than atherosclerotic heart
      disease as the cause of death at autopsy among blacks compared with whites in New
      York City, whereas atherosclerotic heart disease was more common in whites. These
      findings suggest that ineffective control of hypertension is a major factor
      contributing to excess cardiovascular mortality among urban blacks.

PMID- 9576117
TI  - Interaction between body size and cardiac workload: influence on left ventricular
      mass during body growth and adulthood.
AB  - The development of the left ventricle parallels body growth. During infancy, the
      relation between body size and left ventricular (LV) mass is very close. With
      advancing age, variability of LV mass in relation to body size markedly
      increases. To test the hypothesis that the age-related increase in variability of
      LV mass is due to the progressive impact of hemodynamic stimuli on LV growth,
      quantitative M-mode echocardiograms were obtained in 766 normal-weight,
      normotensive individuals over a range of ages from 1 day to 85 years (330 female
      subjects, 373 subjects younger than 18 years). LV mass was linearly related to
      height2.7 (r2=.69). Prediction of values of LV mass by body size was more
      accurate at birth and progressively less precise with increasing age. Stroke work
      (stroke volume times systolic pressure) was closely related to LV mass (r2=.74).
      The explained variance of LV mass increased from 69% in the univariate regression
      with height2.7 to 82% in a multivariate model including height2.7, stroke work,
      and gender. In children and adolescents (younger than 18 years), height2.7 was
      the main determinant of LV mass, whereas during adulthood stroke work and gender
      were more important predictors of LV mass than height2.7. Thus (1) the influence
      of body growth on development of LV mass decreases after early infancy because of
      both the variability of hemodynamic load and the increasing effect of gender; (2)
      after adolescence, during adulthood, in normotensive, normal-weight individuals,
      the impact of hemodynamic load and male gender on LV mass is greater than the one
      of body size; and (3) an appreciable proportion of variability of LV mass remains
      unexplained with the studied models. This might be due to genotypic variations
      and/or measurement error.

PMID- 9576118
TI  - Sodium induces hypertrophy of cultured myocardial myoblasts and vascular smooth
      muscle cells.
AB  - The mechanisms of sodium-induced myocardial hypertrophy and vascular hypertrophy
      are poorly understood. We tested the hypothesis that a high sodium concentration
      can directly induce cellular hypertrophy. Neonatal rat myocardial myoblasts
      (MMbs) and vascular smooth muscle cells (VSMCs) were cultured in a 50:50 mixture
      of DMEM and M199 supplemented with 10% fetal bovine serum. When the monolayers
      reached approximately 80% confluence, normal sodium medium (146 mmol/L) was
      replaced with high sodium media (152 mmol/L, 160 mmol/L, and 182 mmol/L) for up
      to 5 days. Increasing sodium from a baseline concentration of 146 mmol/L to the
      higher concentrations for 5 days caused dose-related increases in cell mean
      diameter, cell volume, and cellular protein content in both MMbs and VSMCs.
      Increasing the sodium concentration by only 4% (from 146 mmol/L to 152 mmol/L)
      caused the following respective changes in MMbs and VSMCs: 8.5% and 8.7% increase
      in cell mean diameter, 27.6% and 27.0% increase in cell volume, and 55.7% and
      46.7% increase in cellular protein content. The rate of protein synthesis,
      expressed as [3H]leucine incorporation, increased by 87% and 99% in MMbs after
      exposure to 152 mmol/L and 160 mmol/L sodium, respectively, compared with the 146
      mmol/L sodium control group. Exposure of MMbs to medium with a sodium
      concentration of 10% above normal, ie, 160 mmol/L, caused a significant decrease
      (range, 26% to 44%) in the rate of protein degradation at multiple time points
      over a 48-hour period compared with normal sodium control cells. The increase in
      cellular protein content caused by 160 mmol/L sodium returned to normal within 3
      days after MMbs were returned to a normal sodium medium. These findings support
      the hypothesis that sodium has a direct effect to induce cellular hypertrophy and
      may therefore be an important determinant in causing myocardial and/or vascular
      hypertrophy in subjects with increased sodium concentration in the extracellular
      fluid.

PMID- 9576119
TI  - Influence of race and dietary salt on the antihypertensive efficacy of an
      angiotensin-converting enzyme inhibitor or a calcium channel antagonist in salt
      sensitive hypertensives.
AB  - Dietary salt restriction is a recommended adjunct with antihypertensive therapy.
      There may be racial differences in blood pressure response to salt restriction
      while on antihypertensive therapy. We performed a multicenter, randomized, double
      blind, placebo-controlled, parallel-group clinical trial (black, n=96; Hispanic,
      n=63; white, n=232). Participants were initially preselected for stage I to III
      hypertension and then further selected for salt sensitivity (> or = 5 mm Hg
      increase in diastolic blood pressure after 3 weeks of low salt [< or = 88 mmol/d
      Na+] and high salt [>190 mmol/d Na+] diet). We compared the antihypertensive
      effect of an angiotensin-converting enzyme inhibitor (enalapril 5 or 20 mg BID)
      or a calcium channel antagonist (isradipine 5 or 10 mg BID) during alternating
      periods of high and low salt intake. The main outcome measure was blood pressure
      change and absolute blood pressure level achieved with therapy. During the high
      salt diet (314.7+/-107.5 mmol/d urinary Na+) there was greater downward change in
      blood pressure with both enalapril and isradipine compared with the low salt diet
      (90.1+/-50.8 mmol/d Na+); however, the absolute blood pressure achieved in all
      races was consistently lower on a low salt diet for both agents. Black, white,
      and Hispanic isradipine-treated salt-sensitive hypertensives demonstrated a
      smaller difference between high and low salt diets (black, -3.6/-1.6 mmHg; white,
      -6.2/-3.9 mmHg; Hispanic, -8.1/-5.3 mm Hg) than did enalapril-treated patients
      (black, -9.0/-5.3 mm Hg; white, -11.8/-7.0 mm Hg; Hispanic, -11.1/-5.6 mm Hg). On
      the low salt diet, blacks, whites, and Hispanics had similar blood pressure
      control with enalapril and isradipine. On the high salt diet, blacks had better
      blood pressure control with isradipine than with enalapril, whereas there was no
      difference in the blood pressure control in whites and Hispanics treated with
      either drug. Dietary salt reduction helps reduce blood pressure in salt-sensitive
      hypertensive blacks, whites, and Hispanics treated with enalapril or isradipine.
      These data demonstrate that controlling for salt sensitivity diminishes race
      related differences in antihypertensive activity.

PMID- 9576120
TI  - Characterization of a urinary bufodienolide Na+,K+-ATPase inhibitor in patients
      after acute myocardial infarction.
AB  - Recent evidence suggests the existence of several endogenous Na+,K+-ATPase
      inhibitors in mammals. Previously, we have shown that the amphibian Na+,K+-ATPase
      inhibitor marinobufagenin (3,5-dihydroxy-14,15-epoxy bufodienolide) acts as a
      vasoconstrictor in isolated rat and human arteries. Mammalian plasma was shown to
      contain marinobufagenin-like immunoreactive material, which is responsive to
      saline volume expansion. The present study describes purification of a
      bufodienolide, which is similar to marinobufagenin, from the urine of patients
      after acute myocardial infarction with the use of thin-layer chromatography and
      reverse-phase high-performance liquid chromatography (HPLC). The purified
      substance cross-reacted with marinobufagenin antibody, demonstrated maximal UV
      absorbance at 300 nm characteristic of bufodienolides, and eluted from HPLC
      columns with the same retention time as marinobufagenin. Mass spectrometry of
      purified material revealed the presence of a substance indistinguishable from
      amphibian marinobufagenin and having molecular mass of 400 D. The present studies
      show that one of the human digitalis-like factors may have a bufodienolide
      structure and is likely to represent marinobufagenin or its isomer, and they
      suggest a role for this substance in the pathogenesis of myocardial ischemia.

PMID- 9576121
TI  - Kallikrein gene delivery attenuates hypertension and cardiac hypertrophy and
      enhances renal function in Goldblatt hypertensive rats.
AB  - To demonstrate potential therapeutic effects of kallikrein gene delivery, we
      delivered adenovirus (Ad.CMV-cHK) carrying the human tissue kallikrein gene into
      two-kidney, one-clip Goldblatt hypertensive rats. A single intravenous injection
      of the recombinant adenovirus caused a delay of blood pressure increase that
      began 1 day after injection and continued for 24 days. A maximal blood pressure
      reduction was observed in rats receiving kallikrein gene delivery compared with
      control rats receiving Ad.CMV-LacZ (160+/-5 versus 186+/-7 mm Hg, n=6, P<.01).
      The expression of human tissue kallikrein mRNA was identified in the kidney,
      heart, aorta, and liver of rats receiving kallikrein gene delivery.
      Immunoreactive human kallikrein levels were measured in rat serum and urine in a
      time-dependent manner. Adenovirus-mediated kallikrein gene delivery caused a
      significant reduction in the left ventricular mass and cardiomyocyte size, as
      well as an increase in renal blood flow, urine flow, glomerular filtration rates,
      electrolyte output, and urine excretion. Enhanced renal responses were
      accompanied by significant increases in urinary kinin, nitrite/nitrate, and
      cyclic GMP levels. These findings show that the expression of human tissue
      kallikrein via gene delivery has protective effects against renovascular
      hypertension and cardiovascular and renal dysfunction.

PMID- 9576122
TI  - Localization and production of angiotensin II in the isolated perfused rat heart.
AB  - We used a modification of the isolated perfused rat heart, in which coronary
      effluent and interstitial transudate were separately collected, to investigate
      the localization and production of angiotensin II (Ang II) in the heart. During
      combined renin (0.7 to 1.5 pmol Ang I/mL per minute) and angiotensinogen (6 to 12
      pmol/mL) perfusion (4 to 8 mL/min) for 60 minutes (n=3), the steady-state levels
      of Ang II in interstitial transudate in two consecutive 10-minute periods were
      4.3+/-1.5 and 3.6+/-1.5 fmol/mL compared with 1.1+/-0.4 and 1.1+/-0.6 fmol/mL in
      coronary effluent (mean+/-half range). During perfusion with Ang II (n=5), steady
      state Ang II in interstitial transudate was 32+/-19% of arterial Ang II compared
      with 65+/-16% in coronary effluent (mean+/-SD, P<.02). During perfusion with Ang
      I (n=5), Ang II in interstitial transudate was 5.1+/-0.6% of arterial Ang I
      compared with 2.2+/-0.3% in coronary effluent (P<.05). The tissue concentration
      of Ang II in the combined renin/angiotensinogen perfusions (per gram) was as high
      as the concentration in interstitial transudate (per milliliter). Addition of
      losartan (10(-6) mol/L) to the renin/angiotensinogen perfusion (n=3) had no
      significant effect on the tissue level of Ang II, whereas losartan in the
      perfusions with Ang I (n=5) or Ang II (n=5) decreased tissue Ang II to
      undetectably low levels. The results indicate that the heart is capable of
      producing Ang II and that this can lead to higher levels in tissue than in blood
      plasma. Cardiac Ang II does not appear to be restricted to the extracellular
      fluid. This is in part due to AT1-receptor-mediated cellular uptake of
      extracellular Ang II, but our results also raise the possibility of intracellular
      Ang II production.

PMID- 9576123
TI  - Mutations and variants of the epithelial sodium channel gene in Liddle's syndrome
      and primary hypertension.
AB  - Liddle's syndrome is a rare monogenic form of hypertension caused by truncating
      or missense mutations in the C termini of the epithelial sodium channel beta- or
      gamma-subunits. These mutations delete or alter a conserved proline-rich amino
      acid sequence referred to as the PY-motif. We report here a Liddle's syndrome
      family with a betaArg564X mutation with a premature stop codon deleting the PY
      motif of the beta-subunit. This family shows marked phenotypic variation in blood
      pressure, serum potassium levels, and age of onset of hypertension. Given the
      similarity with primary hypertension, changes in the C termini of the beta- or
      gamma-subunits may contribute to the development of primary hypertension or to
      hypertension associated with diabetic nephropathy. Accordingly, the coding
      sequences for the cytoplasmic C termini of the beta- and gamma-subunits were
      screened for mutations with the use of polymerase chain reaction, single-strand
      conformation polymorphism, and direct DNA sequencing in 105 subjects with primary
      hypertension and 70 subjects with diabetic nephropathy. One frequent polymorphism
      was identified, but its frequency did not differ among subjects with primary
      hypertension, subjects with diabetic nephropathy, or control subjects. Two of the
      175 subjects with primary hypertension or diabetic nephropathy showed variants
      that were not present in 186 control subjects. None of the variants changed the
      PY-motif sequence. In conclusion, a betaArg564X mutation is the likely cause of
      Liddle's syndrome in this Swedish family, but it is unlikely that mutations in
      the beta- and gamma-subunit genes of the epithelial sodium channel play a
      significant role in the pathogenesis of primary hypertension or diabetic
      nephropathy.

PMID- 9576124
TI  - Single L-type calcium channels in smooth muscle cells from resistance arteries of
      spontaneously hypertensive rats.
AB  - The amplitude of the whole-cell L-type Ca2+ channel current recorded from
      vascular smooth muscle cells is reportedly greater in spontaneously hypertensive
      rats (SHR) than in Wistar-Kyoto rats (WKY). However, no study has examined
      properties of single Ca2+ channels in arterial cells from these strains. To
      further test the hypothesis that activation of L-type Ca2+ channels in arterial
      smooth muscle cells would be enhanced in SHR, we recorded single Ca2+ channel
      currents in resistance mesenteric artery cells from SHR and WKY (8 to 9 weeks of
      age) using a cell-attached patch clamp technique. With 50 mmol/L Ba2+ in the
      recording pipette, the depolarizing pulse from a holding potential of -40 mV
      evoked the single L-type Ca2+ channel current. Opening of the single channels was
      more frequent in cells from SHR than from WKY. Single-channel conductance (20 pS)
      and open time (1 ms at 0 mV) did not differ in the two strains. The results
      suggest that an increased amplitude of the whole-cell current can be attributed
      to the enhanced opening of single Ca2+ channels in the arterial smooth muscle
      cells from SHR compared with WKY.

PMID- 9576125
TI  - Seven-year incidence of hypertension in a cohort of middle-aged African Americans
      and whites.
AB  - Many studies have suggested that African Americans have a higher prevalence of
      hypertension than whites. The authors conducted a prospective study of
      hypertension incidence from 1987-1988 to 1994-1995 in 140 African American and
      237 white adults aged 30 to 54 years at baseline. The study participants were
      screened for participation in the Trials of Hypertension Prevention, phase 1, an
      18-month lifestyle modification intervention trial aimed at lowering blood
      pressure, at the Baltimore Clinical Center. Baseline age, blood pressure, body
      mass index, and heart rate were similar in the two groups. Compared with whites,
      however, African Americans had a lower percentage of men, college graduates, and
      households with an income > or = $40,000 per year. African Americans also had
      lower mean urinary sodium to creatinine ratio and potassium to creatinine ratio,
      but a similar sodium to potassium ratio. The incidence of hypertension (blood
      pressure > or = 160/95 mm Hg and/or taking antihypertensive medication) over 7
      years of follow-up was nearly identical: 25.7% in African Americans and 25.3% in
      whites. Baseline age, gender, blood pressure, and heart rate were all associated
      with the incidence of hypertension. Even after adjustment for these covariables,
      the risk of hypertension was not higher in African Americans compared with
      whites. These results indicate that middle-aged African Americans and whites have
      a similar risk of developing hypertension given the same age, initial blood
      pressure, and body mass index at baseline.

PMID- 9576126
TI  - Knowledge, attitudes, and practices on hypertension in a country in
      epidemiological transition.
AB  - Assessment of knowledge, attitudes, and practices (KAP) is a crucial element of
      hypertension control, but little information is available from developing
      countries where hypertension has lately been recognized as a major health
      problem. Therefore, we examined KAP on hypertension in a random sample of 1067
      adults aged 25 to 64 years from the Seychelles Islands (Indian Ocean). KAP were
      assessed from an administered structured questionnaire. The age-standardized
      prevalence of hypertension (screening blood pressure [BP] > or = 160/95 mm Hg or
      taking antihypertensive medication) was 36% in men and 25% in women aged 25 to 64
      years. Among hypertensive persons, 50% were aware of the condition, 34% were
      treated, and 10% had controlled BP (ie, BP <160/95 mm Hg). Most persons, whether
      nonhypertensive, unaware hypertensive, or aware hypertensive, had good basic
      knowledge related to hypertension determinants and consequences, possibly an
      effect of a nationwide cardiovascular disease prevention program over the last
      years. However, favorable outcome expectation, positive attitudes, and
      appropriate practices for hypertension and relevant healthy lifestyles were found
      in smaller proportions of participants, with little difference between aware
      hypertensives, unaware hypertensives, and nonhypertensives. Furthermore,
      hypertensive persons with other concurrent cardiovascular risk factors affecting
      the overall heart risk knew well the detrimental effects of these other factors
      but reported making little actual change to control them (particularly regarding
      overweight and sedentary habits). These data point to the need to maximize the
      efficiency of hypertension prevention and control programs so that delay in
      achieving effective hypertension control is minimized in countries experiencing
      recent emergence of hypertension as a major public health problem.

PMID- 9576127
TI  - Treatment with enalapril modifies the pain perception pattern in hypertensive
      patients.
AB  - The cardiovascular system shares numerous anatomic and functional pathways with
      the antinociceptive network. The aim of this study was to investigate whether
      angiotensin-converting enzyme (ACE) inhibitor treatment could affect hypertension
      related hypalgesia. Twenty-five untreated hypertensive patients, together with a
      control group of 14 normotensive subjects, underwent dental pain perception
      evaluation by means of a pulpar test (graded increase of test current applied to
      healthy teeth). After the evaluation of the dental pain threshold (occurrence of
      pulp sensation) and tolerance (time when the subjects asked for the test to be
      stopped), all the subjects underwent a 24-hour ambulatory blood pressure
      monitoring. The hypertensive group then was treated with 20 mg/d enalapril,
      whereas the normotensive subjects remained without any treatment. After a time
      interval of 6+/-2 months, the dental pain sensitivity was retested in all the
      subjects, and ambulatory blood pressure was recorded during treatment in the
      hypertensive patients. At the first assessment, hypertensive patients showed a
      higher pain threshold than normotensive subjects (P<.001). On retesting of pain
      sensitivity in hypertensive patients, a significant decrease of both pain
      threshold and tolerance, leading to their normalization, was observed during
      treatment (P<.001 and P<.005, respectively), in the presence of reduced 24-hour
      and office blood pressure values. A slight, though significant, correlation was
      observed between variations in pain tolerance and baseline blood pressure changes
      occurring during treatment. During follow-up, the normotensive subjects did not
      show any significant pain perception or office blood pressure changes.
      Hypertension-related hypalgesia was confirmed. Mechanisms acting both through
      lowering of blood pressure and specific pharmacodynamic properties may account
      for the normalization of pain sensitivity observed in hypertensive patients
      during treatment with ACE inhibitors.

PMID- 9576128
TI  - Role of mitogen-activated protein kinase in the angiotensin II-induced DNA
      synthesis in vascular smooth muscle cells.
AB  - The activation of mitogen-activated protein (MAP) kinase and increase in
      intracellular free calcium concentration ([Ca2+]i) are discussed in reference to
      activation of different protein kinases and growth of vascular smooth muscle
      cells (VSMCs). The aim of the present study was to investigate the role of
      angiotensin (Ang) II-induced increase in [Ca2+]i for activation of 44-kD/42-kD
      MAP kinase (p44mapk/p42mapk) and DNA synthesis in VSMCs. Experiments were
      performed by chelation of [Ca2+]i by the intracellular chelator 1,2-bis-(o-amino
      5-methylphenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester
      (MAPTAM). Ca2+ was measured by the fura 2 method. MAP kinase activation was
      determined by the Western blotting method. DNA synthesis was determined by
      measurement of [3H]thymidine incorporation into the cell DNA. Treatment of VSMCs
      with 20 micromol/L MAPTAM for 30 minutes resulted in a complete abolishment of
      the maximal Ang II-induced increase at 10 seconds. Ang II phosphorylated the
      p44mapk/p42mapk in a time-dependent manner, showing a maximum at 3 minutes. In
      MAPTAM-treated cells, the maximal phosphorylation of MAP kinase isoforms was
      shifted to 5 minutes, and dephosphorylation was delayed compared with untreated
      cells. In concordance with this finding, the induction of the MAP kinase
      phosphatase-1 was markedly impaired in MAPTAM-treated cells. Ang II induced a 2.3
      fold increase in [3H]thymidine incorporation into DNA synthesis in untreated
      cells. This effect was not reduced in MAPTAM-treated cells. Treatment of the
      cells with PD 98059 (10 micromol/L), a MAP kinase kinase inhibitor, caused 85%
      inhibition of the Ang II-induced activation of MAP kinases but did not inhibit
      the Ang II-induced DNA synthesis. In conclusion, the Ang II-induced stimulation
      of the MAP kinase is a Ca2+-dependent process. Furthermore, blockade of the Ang
      II-induced stimulation of the early intracellular events, such as increase in
      [Ca2+]i or phosphorylation of the MAP kinase, is not accompanied by an inhibition
      of the Ang II-induced DNA synthesis.

PMID- 9576129
TI  - Vascular beta-adrenergic receptor adenylyl cyclase system from renin-transgenic
      hypertensive rats.
AB  - In transgenic rats harboring the mouse Ren-2d gene [TG(mREN2)27], downregulation
      of the myocardial beta-adrenergic receptor adenylyl cyclase system has been
      demonstrated previously. Because a reduced vasodilatory reactivity may
      significantly contribute to hypertension in this model of an activated tissue
      renin-angiotensin system, the present study investigated alterations of the
      vascular beta-adrenergic receptor adenylyl cyclase system. In freshly harvested
      aortas from transgenic rats, the activity of adenylyl cyclase was reduced
      significantly (P<.05) in the presence of isoprenaline (10 micromol/L; -28+/
      4.5%), guanosine 5'-triphosphate, 5'-guanylylimidodiphosphate [Gpp(NH)p] (100
      micromol/L; -29+/-4.7%), and forskolin (100 micromol/L) with (-42+/-6%) and
      without (-40+/-4.3%) MnCl2. Densities of beta-adrenoceptors were similar in both
      strains. In situ hybridization demonstrated the expression of the transgene in
      aortic smooth muscle cells. These data indicate a reduced catalyst function as a
      major contributing factor involved in the maintenance of high blood pressure in
      TG(mREN2)27. However, in cultivated aortic smooth muscle cells, cAMP production
      after stimulation with isoprenaline, forskolin, and Gpp(NH)p in the presence or
      absence of MnCl2 was not different. Affinities and densities of beta
      adrenoceptors and amounts of immunochemically detected inhibitory and stimulatory
      G-protein alpha-subunits were unchanged. Desensitization after incubation with 10
      micromol/L isoprenaline for 72 hours was identical in smooth muscle cells from
      both strains. Cell cultivation and isoprenaline treatment had no effect on
      transgene expression. We concluded that in transgenic rats the downregulation of
      the aortic beta-adrenergic adenylyl cyclase system is due to humoral and
      hemodynamic factors present in vivo rather than to transgenicity itself.

PMID- 9576130
TI  - Intravenous injection with antisense oligodeoxynucleotides against
      angiotensinogen decreases blood pressure in spontaneously hypertensive rats.
AB  - In the renin-angiotensin system, renin is known to cleave angiotensinogen to
      generate angiotensin I, which is the precursor of angiotensin II. Angiotensin II
      is a vasoactive peptide that plays an important role in blood pressure. On the
      other hand, the liver is the major organ responsible for the production of
      angiotensinogen in spontaneously hypertensive rats (SHR). To test the hypothesis
      that a reduction of angiotensinogen mRNA in the liver by antisense
      oligodeoxynucleotides (ODNs) may affect both plasma angiotensinogen and
      angiotensin II levels, as well as blood pressure, we intravenously injected
      antisense ODNs against rat angiotensinogen coupled to asialoglycoprotein carrier
      molecules, which serve as an important regulator of liver gene expression, into
      SHR via the tail vein. The SHR used in the present study were studied at 20 weeks
      of age and were fed a standard diet throughout the experiment. Plasma
      angiotensinogen, angiotensin II concentrations, and blood pressure all decreased
      from the next day until up to 5 days after the injection of antisense ODNs. These
      concentrations thereafter returned to baseline by 7 days after injection. A
      reduction in the level of hepatic angiotensinogen mRNA was also observed from the
      day after injection until 5 days after injection with antisense ODNs. However, in
      the SHR injected with sense ODNs, plasma angiotensinogen, angiotensin II
      concentrations, and blood pressure, as well as hepatic angiotensinogen mRNA, did
      not significantly change throughout the experimental period. Although the exact
      role of angiotensinogen in hypertension still remains to be clarified, these
      findings showed that intravenous injection with antisense ODNs against
      angiotensinogen coupled to asialoglycoprotein carrier molecules targeted to the
      liver could thus inhibit plasma angiotensinogen levels and, as a result, induce a
      decrease in blood pressure in SHR.

PMID- 9576131
TI  - Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle
      cells of AT1A receptor-deficient mice.
AB  - Our studies on angiotensin II receptor subtype 1A (AT1A) knockout mice define how
      endogenous receptors other than AT1A receptors stimulate changes in cytosolic
      calcium concentration ([Ca2+]i) in cultured aortic vascular smooth muscle cells
      (VSMCs). Wild-type cells have a 1.7 ratio of AT1A/AT1B receptor mRNA as
      determined by semiquantitative reverse transcriptase-polymerase chain reaction.
      Mutant cells express AT1B receptor mRNA but not that for the AT1A receptor. In
      wild-type cells with AT1A present, Ang II (10(-7) mol/L) produces a
      characteristic rapid peak increase in [Ca2+]i of 150 to 180 nmol/L, followed by a
      plateau phase characterized by a sustained 70 to 80 nmol/L increase in [Ca2+]i.
      An unexpected finding was that the magnitude and time-dependent pattern of
      [Ca2+]i changes produced by Ang II were similar in cells that lacked AT1A
      receptors but possessed AT1B receptors. The response in mutant cells indicates
      effective coupling of an Ang II receptor to one or more second messenger systems.
      The similarity of response patterns between cells with and without AT1A receptors
      suggests that non-AT1A receptors are functionally linked to similar signal
      transduction pathways in mutant cells. The fact that mutant and wild-type cells
      exhibit similar patterns of calcium mobilization and entry supports the notion
      that AT1A and non-AT1A receptors share common signal transduction pathways. The
      AT2 receptor ligands PD-123319 and CGP-42112 do not alter Ang II effects in
      either VSMC type, suggesting a paucity of AT2 receptors and/or an absence of
      their linkage to [Ca2+]i pathways. The nonpeptide AT1 receptor blocker losartan
      antagonizes Ang II-induced [Ca2+]i increases in both cell groups, supporting
      mediation by native AT1B receptors and effective coupling of this subtype to
      second messenger systems leading to calcium entry and mobilization. Our results
      demonstrate that Ang II causes calcium signaling in AT1A-deficient VSMCs that is
      mediated by an endogenous losartan-sensitive AT1B receptor.

PMID- 9576132
TI  - N(N)-nicotinic blockade as an acute human model of autonomic failure.
AB  - Pure autonomic failure has been conceptualized as deficient sympathetic and
      parasympathetic innervation. Several recent observations in chronic autonomic
      failure, however, cannot be explained simply by loss of autonomic innervation, at
      least according to our current understanding. To simulate acute autonomic
      failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6+/
      0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32+/-3 years, 68+/-4 kg,
      171+/-5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete
      interruption of sympathetic and parasympathetic efferents as indicated by a
      battery of autonomic function tests. With trimethaphan, small postural changes
      from the horizontal were associated with significant blood pressure changes
      without compensatory changes in heart rate. Gastrointestinal motility, pupillary
      function, saliva production, and tearing were profoundly suppressed with
      trimethaphan. Plasma norepinephrine level decreased from 1.1+/-0.12 nmol/L (180+/
      20 pg/mL) at baseline to 0.23+/-0.05 nmol/L (39+/-8 pg/mL) with trimethaphan
      (P<.001). There was a more than 16-fold increase in plasma vasopressin (P<.01)
      and no change in plasma renin activity. We conclude that blockade of N(N)
      cholinergic receptors is useful to simulate the hemodynamic alterations of acute
      autonomic failure in humans. The loss of function with acute N(N)-cholinergic
      blockade is more complete than in most cases of chronic autonomic failure. This
      difference may be exploited to elucidate the contributions of acute denervation
      and chronic adaptation to the pathophysiology of autonomic failure. N(N)
      Cholinergic blockade may also be applied to study human cardiovascular physiology
      and pharmacology in the absence of confounding baroreflexes.

PMID- 9576133
TI  - Difference between clinic and daytime blood pressure is not a measure of the
      white coat effect.
AB  - The purpose of the present study was to evaluate whether the difference between
      blood pressure measured in the clinic or physician's office and the average
      daytime blood pressure accurately reflects the blood pressure response of the
      patient to the physician ("white coat effect" or "white coat hypertension"). We
      studied 28 hypertensive outpatients (mean age, 41.8+/-11.2 years; age range, 21
      to 64 years) of 35 consecutive patients attending our hypertension clinic, in
      whom (1) continuous noninvasive finger blood pressure was recorded before and
      during the visit, (2) blood pressure was measured according to the Riva-Rocci
      Korotkoff method (mercury sphygmomanometer) with the patient in the supine
      position, and (3) daytime ambulatory blood pressure was monitored with a
      SpaceLabs 90207 device. The peak blood pressure increase recorded directly during
      the visit was compared with the difference between clinic and daytime average
      ambulatory blood pressures. Compared with previsit values, peak increases in
      finger systolic and diastolic blood pressures during the visit to the clinic were
      38.2+/-3.1 and 20.7+/-1.6 mm Hg, respectively (mean+/-SEM, P<.01 for both).
      Daytime average systolic and diastolic blood pressures were 135.5+/-2.5 and
      89.2+/-1.9 mm Hg, with both lower than the corresponding clinic blood pressure
      values (146.6+/-3.6 and 94.9+/-2.2 mm Hg, P<.01). These differences, however,
      were <30% of the peak finger blood pressure increases during the physician's
      visit, to which these increases showed no relation. Although the visit to the
      physician's office was associated with tachycardia (9.0+/-1.6 bpm, P<.01), there
      was no difference between clinic and daytime average heart rates. These data
      indicate that the clinic-daytime average blood pressure difference does not
      reflect the alerting reaction and the pressure response elicited by the
      physician's visit and thus is not a reliable measure of the white coat effect.

PMID- 9576134
TI  - Ethnic differences in the hypertensive heart and 24-hour blood pressure profile.
AB  - Black hypertensive persons have been observed to have a greater degree of left
      ventricular hypertrophy than white hypertensives. However, previous studies have
      matched groups for blood pressure (BP) measured in the clinic, and it has been
      demonstrated that black hypertensives have an attenuated nocturnal BP dip. Clinic
      BPs may thus underestimate mean 24-hour BP in this group. To investigate whether
      the differences in left ventricular hypertrophy can be accounted for by the
      greater mean 24-hour BP in black hypertensives, 92 previously untreated
      hypertensives were studied with 24-hour ambulatory BP monitoring and
      echocardiography. The 46 black hypertensives (24 men and 22 women) were matched
      with the 46 white hypertensives for age, gender, and mean 24-hour BP. Despite
      similar mean 24-hour BPs (blacks, 142/93 mm Hg; whites, 145/92 mm Hg; P=.53/.66),
      the black group had a smaller mean nocturnal dip than the white group (blacks,
      8/8 mm Hg; whites, 16/13 mm Hg; P<.01). In addition, mean left ventricular mass
      index (LVMI) was greater (blacks, 130 g/m2; whites, 107 g/m2; P<.001). Mean 24
      hour systolic BP was significantly related to LVMI in both groups (blacks, r=.45,
      P<.01; whites, r=.56, P<.01). However, systolic BP dip correlated inversely with
      LVMI only in the black group (blacks, r=-.30, P<.04; whites, r=.05, P=.76). In a
      multiple regression model, LVMI was independently related to both mean daytime BP
      and mean nocturnal BP dip in black subjects but only to mean daytime BP in white
      subjects. In conclusion, the increased left ventricular hypertrophy observed in
      black hypertensives compared with white hypertensives is not accounted for by
      differences in mean 24-hour BP. However, LVMI in black hypertensives appears to
      be more dependent on nocturnal BP than that in white hypertensives; this, coupled
      with the attenuated BP dip in black hypertensives, suggests that the BP profile
      rather than 24-hour BP may be important in determining the differences in left
      ventricular hypertrophy.

PMID- 9576135
TI  - Effects of a novel antihypertensive drug, cilnidipine, on catecholamine secretion
      from differentiated PC12 cells.
AB  - Effects of a novel dihydropyridine type of antihypertensive drug, cilnidipine, on
      the regulation of the catecholamine secretion closely linked to the intracellular
      Ca2+ were examined using nerve growth factor (NGF)-differentiated rat
      pheochromocytoma PC12 cells. By measuring catecholamine secretion with high
      performance liquid chromatography coupled with an electrochemical detector, we
      showed that high K+ stimulation evoked dopamine release from PC12 cells both
      before and after NGF treatments. Cilnidipine depressed dopamine release both from
      NGF-treated and untreated PC12 cells in a concentration-dependent manner. In
      contrast, inhibition by nifedipine was markedly decreased in the differentiated
      PC12 cells. With intracellular Ca2+ concentration ([Ca2+]i) measurements using
      fura 2, the elevation of high K+-evoked [Ca2+]i was separated into nifedipine
      sensitive and -resistant components. The nifedipine-resistant [Ca2+]i increase
      was also blocked by cilnidipine, as well as omega-conotoxin-GVIA. By the use of
      the conventional whole-cell patch-clamp technique, the compositions of the high
      voltage-activated Ca2+ channel currents in the NGF-treated PC12 cells were
      divided into types: L-type, N-type, and residual current components. It was also
      estimated that cilnidipine at 1 and 3 micromol/L strongly blocked the N-type
      current without affecting the residual current. These results suggest that
      cilnidipine inhibits catecholamine secretion from differentiated PC12 cells by
      blocking Ca2+ influx through the N-type Ca2+ channel, in addition to its well
      known action on the L-type Ca2+ channel.

PMID- 9576136
TI  - Noninvasive assessment of flow-mediated vasodilation with 30-MHz transducer in
      pregnant women.

PMID- 9576137
TI  - Is plasma Ac-SDKP level a reliable marker of chronic angiotensin-converting
      enzyme inhibition in hypertensive patients?

PMID- 9576138
TI  - A wheeze by any other name is (not) the same: the role of symptom perception in
      asthma.

PMID- 9576139
TI  - Symptom perception in asthma: a multidisciplinary review.
AB  - Clinical observations and research show that symptom perception in asthma is, at
      worst, inaccurate or often biased in two directions: (1) blunted perception, (2)
      overperception (both involving airway obstruction manifested in low or high
      breathlessness). Theoretically breathlessness occurs during respiratory labor or
      blood gas changes. However, pathophysiological factors and asthma severity are
      inconsistently related to perceptual accuracy. Consequently, symptom perception
      within the biomedical perspective is not well understood. Possible psychological
      influences, varying from the stimulus level to emotions and high-order reasoning,
      are discussed.

PMID- 9576140
TI  - Comparison of a new multidose powder inhaler (Diskus/Accuhaler) and the
      Turbuhaler regarding preference and ease of use.
AB  - Many patients with asthma or chronic obstructive pulmonary disease (COPD) use
      their inhaler ineffectively. Several studies revealed that inhaler-specific
      design features contributed significantly to the failure rate, which clearly
      demonstrates the need for developing more "foolproof" inhalers. This study
      compared ease of use and patient preference of the Diskus/Accuhaler (DA) with the
      Turbuhaler (TH). Fifty patients with asthma or COPD aged 15 years and older were
      included in a randomized, crossover comparison of DA with TH regarding patient
      preference and ease of use. All had to be naive to DA and TH, but currently had
      to be using inhaled medication with another device. Inhalation technique was
      assessed using inhaler-specific checklists and patients had to state a preference
      for DA or TH regarding various aspects, as well as overall preference. With DA 46
      patients (92%) made no errors regarding essential inhalation maneuvers, compared
      to 37 patients (74%) using TH (p = 0.023). This difference is exclusively caused
      by not loading the TH properly. When patients were asked which inhaler they would
      prefer, 17 wanted the DA, 25 the TH, and 8 did not state a preference. The
      difference was not significant. TH was favored over DA regarding factors related
      to size and the number of available dosages. The counting mechanism of the DA was
      preferred over the TH. It seems that patients have a clear, although not
      statistically significant, preference for TH, but with the DA fewer patients make
      crucial errors.

PMID- 9576142
TI  - Outcomes analysis of a summer asthma camp.
AB  - Forty children with moderate to severe asthma were enrolled in an asthma camp.
      Changes in peak flow meter (PFM) and metered-dose inhaler (MDI) technique, health
      care utilization, and school absenteeism were evaluated. The mean post-PFM score
      at the end of camp (8.9 +/- 0.3) was significantly higher (p < .0001) than the
      pre PFM score (6.0 +/- 3.4). The mean post-MDI score (6.5 +/- 1.5) was
      significantly higher (p < 0.0001) than the pre-MDI score (4.1 +/- 1.8). Emergency
      room visits decreased by 59%, hospitalizations decreased by 83%, and school
      absenteeism decreased from 266 to 188 days. Health care savings totaled $2014 per
      child enrolled.

PMID- 9576143
TI  - Evaluation of aerosol drug output from the OptiChamber and AeroChamber spacers in
      a model system.
AB  - Metered-dose inhalers (MDIs) are an effective means of generating drug-containing
      aerosols targeted for delivery to intrapulmonary airways. Many problems
      associated with incorrect patient use of MDIs are mitigated by adding a valved
      spacer device to the inhaler mouthpiece. This in vitro study compared the
      efficiency of drug output through a new spacer device, OptiChamber (HealthScan
      Products Inc., Cedar Grove, NJ), to that of a device commercially available since
      the 1980s, AeroChamber (Monaghan Medical, Plattsburgh, NY). Testing utilized MDI
      formulations of albuterol, beclomethasone dipropionate, and cromolyn sodium.
      OptiChamber equaled or, in the majority of cases, exceeded AeroChamber in output
      of the three drugs at two simulated inspiratory flow rates. Drug output from
      OptiChamber was found to be less sensitive to changes in flow rate than that from
      AeroChamber. OptiChamber also showed less decrease in drug output than
      AeroChamber when time delays were introduced between MDI actuation and the start
      of a simulated inhalation. Mass median aerodynamic diameters of drugs exiting the
      two spacers were generally similar to those of drugs exiting the MDI alone.
      However, spacers were shown to nearly eliminate the output of large-size drug
      particles (>5.8 microm), which can result in oropharyngeal drug deposition.
      Emitted fine-particle drug (<5.8 microm) doses from OptiChamber were greater than
      those from AeroChamber with or without a delay between canister actuation and the
      start of a simulated inhalation. The results suggest that OptiChamber may provide
      more efficacious aerosol drug delivery than AeroChamber under both ideal and
      suboptimal conditions.

PMID- 9576141
TI  - Dose-related response to inhaled fluticasone propionate in patients with
      methacholine-induced bronchial hyperresponsiveness: a double-blind, placebo
      controlled study.
AB  - Dose-response relationships with inhaled corticosteroids in the treatment of
      asthma have been difficult to establish. A multicenter, double-blind, parallel
      group study was conducted to evaluate the clinical efficacy and safety of low
      doses of inhaled fluticasone propionate (FP) in patients with mild to moderate
      asthma. Methacholine challenge testing was conducted in addition to measurement
      of traditional efficacy variables. After a single-blind screening period, 138
      patients > or = 12 years of age were randomly assigned to receive placebo, FP 50
      microg, or FP 100 microg, twice daily for 8 weeks. The results of methacholine
      challenge testing averaged over all visits favored FP 200 microg/day over placebo
      and FP 100 microg/day (p < 0.05); there were no significant differences between
      placebo and FP 100 microg/day. Mean changes from baseline to endpoint favored
      each dose of FP over placebo based on forced expiratory volume in 1 sec (FEV1),
      patient-measured peak expiratory flow (PEF), total symptom scores, and rescue
      bronchodilator use (p < 0.05); there were no differences in these parameters
      between the two doses of FP. The addition of methacholine challenge testing
      allowed definition of a dose-response relationship that was not apparent with
      traditional efficacy variables.

PMID- 9576144
TI  - Functional activity of bronchi from an organ donor with fatal asthma: studies on
      cryopreserved bronchi.
AB  - Human bronchi were taken from the lungs of a single asthmatic and 5 nonasthmatic
      organ donors. The tissues were slowly frozen to -70 degrees C and stored for 1-28
      months in liquid nitrogen (-196 degrees C) while suspended in Krebs-Henseleit
      solution containing 1.8 M dimethyl sulfoxide and 0.1 M sucrose as
      cryoprotectants. After thawing, bronchial rings were suspended in 10 ml organ
      baths for isometric tension recording. Spontaneously developed tone (1.13 +/-
      0.12, n = 22, vs. 0.56 +/- 0.07 g, n = 33, p < 0.001) and maximal contractile
      responses to histamine (1.93 +/- 0.12, n = 34, vs. 1.02 +/- 0.14 g, n = 30, p <
      0.001) were significantly stronger in asthmatic than in nonasthmatic bronchi. The
      potency of histamine was 4 times less in asthmatic than in nonasthmatic bronchi
      (p < 0.001). Comparison of the maximal responses to histamine after storage at 
      196 degrees C for up to 28 months revealed no significant reduction of the
      contractile function by time of cryostorage. Salbutamol and the potassium channel
      opener SDZ PCO 400 were 3-4 times less potent in asthmatic than in nonasthmatic
      bronchi. For antagonism of histamine by ketotifen in asthmatic bronchi (pD'2 =
      8.04 +/- 0.13, n = 5) 4 times higher concentrations were necessary than in
      nonasthmatic bronchi (pD'2 = 8.63 +/- 0.06, n = 15, p < 0.001). These data
      support the contention that in spite of a diminished sensitivity to histamine
      after fatal asthma, isolated bronchi show enhanced spontaneous and agonist
      induced contractile responses whereas relaxant responses appear to be impaired.

PMID- 9576145
TI  - The profile of the cytokines secreted during the generation of T-helper cells
      from atopic asthmatic subjects.
AB  - This study investigated cytokine release by T-cell lines from atopic and
      nonatopic individuals in the presence of specific aeroallergen. Cell lines from
      atopic and nonatopic individuals secreted IL-2 for less than 14 and more than 21
      days, respectively. All of the atopic, but not the nonatopic, cell lines
      exhibited a biphasic peak in IL-4 and IL-5 secretion. Flow cytometry revealed
      that, after 35 days, 89.3% of the atopic cells were T helpers and 73.2% were
      activated. Only 7.4% of the nonatopic cells displayed activation markers. In
      conclusion, T-cell differentiation may be controlled by other factors in addition
      to stimulation by aeroallergens.

PMID- 9576146
TI  - Asthma prevalence and risk factors in selected Head Start sites in Chicago.
AB  - Prevalence of and risk factors for asthma were examined in 1085 Head Start
      families at 18 Head Start sites in four high-risk community areas in 1994. A
      total of 13.9% of the families reported diagnosed asthma in their Head Start
      child and 18.8% reported that their child wheezed in the last 12 months. A total
      of 26.9% of respondents reported asthma in the immediate family of the child. Low
      birth weight (1500-2499 g), very low birth weight (<1500 g), and self-reported
      exposure to dampness or mold in the last 12 months were significantly associated
      with self-reported diagnosed asthma (OR = 1.93; 95% CI 1.17-8.73), (OR = 4.5; 95%
      CI 1.25-16.3), and (OR = 1.94; 95% CI 1.23-3.04), respectively. The young age of
      the children in Head Start, as well as the high prevalence of asthma in their
      families, suggest that the Head Start programs offer an unusual opportunity for
      asthma prevention programs.

PMID- 9576147
TI  - Age and the impacts of triggers in childhood asthma.
AB  - This study examined the relationships among age (2-20 years) and the impacts of
      12 common triggers in episodes of childhood asthma. The triggers were: air
      pollution, allergy problems, cigarette smoke, stress or worry, anger, excitement,
      laughter, high/low environmental temperature, high humidity, respiratory
      infection, nighttime hours, and physical activity. Data were analyzed from
      families with asthmatic children (n = 119) as part of a larger study of
      biological and psychosocial factors in asthma and other illnesses. Positive
      correlations were found for age and the trigger impacts of allergy problems (p =
      0.025) and physical activity (p = 0.004); negative correlations were found for
      age and the trigger impacts of nighttime hours (p = 0.002) and respiratory
      infection (p = 0.002). Age was also negatively correlated with the frequency of
      recent respiratory infections (p = 0.000) and positively correlated with the
      intensity of hay fever episodes (p = 0.047). These findings indicate that as
      children with asthma get older, their asthma episodes are more likely to be
      influenced by allergy problems and physical activity, and less likely to be
      associated with nighttime hours and respiratory infections.

PMID- 9576148
TI  - Serum level of eosinophil cationic protein in patients with chronic cough:
      relationship to blood eosinophils and airway hyperresponsiveness.
AB  - We measured the serum level of eosinophil cationic protein (ECP), determined the
      blood eosinophil count, and assessed pulmonary function by spirometry and airway
      responsiveness to methacholine in 80 patients with a cough lasting longer than 3
      weeks without an obvious cause. The serum level of ECP was above the cutoff value
      of 15.7 ng/mL (mean + 2 SD in 105 healthy control adults) in 30 (37.5%) of 80
      patients (high-serum-ECP group). The blood eosinophil count was significantly
      higher in the high-serum-ECP group than in the normal-serum-ECP group (p < 0.01).
      The cumulative dose of methacholine causing a 35% decrease in respiratory
      conductance (PD35Grs) was significantly lower in the high-serum-ECP group than in
      the normal-serum-ECP group (p < 0.001). The serum concentration of ECP was
      correlated with the blood eosinophil count and the PD35Grs (r = 0.59, p < 0.001
      and r = -0.48, p < 0.001, respectively). These findings suggest a possible role
      for serum level of ECP in management of patients with chronic cough.

PMID- 9576149
TI  - Diurnal variation of peak expiratory flow in children with cough variant asthma.
AB  - Cough variant asthma (CVA) is thought to be a variant form of asthma in which
      cough is the sole clinical manifestation of airways hyperresponsiveness, a
      characteristic feature of asthma. Another characteristic feature of asthma
      includes an increased diurnal variation of peak expiratory flow (PEF) compared to
      normal subjects. To examine whether diurnal variation of PEF might also increase
      in children with CVA, we have examined the degree of diurnal variation of PEF in
      these children (n = 7) by measuring peak flow serially for a week, and compared
      it with those in mild to moderate asthma (n = 17) and in control children without
      cough (n = 8). In control children without cough, the average value of the mean
      diurnal variation of PEF was 10.4 +/- 0.8%. In both groups of children with
      asthma and with CVA, there was a significant increase in the value (20.5 +/- 1.3%
      and 23.6 +/- 3.6%, respectively) compared to that in control children (p < 0.01
      in both groups), although there was no significant difference between these 2
      groups. These results show that mild, but significant airway obstruction is
      occurring in children with CVA, although clinical wheezing is not recognized.
      Serial measurements of diurnal variation of PEF may be helpful for the diagnosis
      of CVA in children.

PMID- 9576150
TI  - Heparin is more effective than inogatran, a low-molecular weight thrombin
      inhibitor in suppressing ischemia and recurrent angina in unstable coronary
      disease. Thrombin Inhibition in Myocardial Ischemia (TRIM) Study Group.
AB  - Thrombin has been suggested as one of the main pharmacologic targets in unstable
      coronary syndromes. Electrocardiographic signs of ischemia during continuous
      monitoring convey prognostic information in these patients. This study assessed
      the anti-ischemic and clinical effects of the novel low-molecular weight thrombin
      inhibitor inogatran in patients with unstable angina and non-Q-wave infarction
      without persistent ST-segment elevation on hospital admission. Within 24 hours of
      the last episode of chest pain, 324 patients were randomized to 72 hours of
      treatment with inogatran or heparin. Continuous ST-segment analysis with
      computerized vectorcardiography was used to monitor ischemia for 24 hours. The
      occurrence of cardiac events during the first 7 days were studied and compared
      with ischemic episodes during the initial 24 hours. The heparin-treated patients
      had less episodes of ischemia (ST vector magnitude [ST-VM]: 1 +/- 2.6 vs 2 +/-
      4.5, p < 0.001 and ST change vector magnitude [STC-VM]: 3 +/- 4.7 vs 6 +/- 7.6, p
      < 0.001) than the patients receiving inogatran. This was paralleled by a lower
      incidence of the combined end point of death, nonfatal infarction, refractory or
      recurrent angina during the first 7 days for the heparin-treated patients (35%)
      compared with the inogatran-treated patients (50%) (p < 0.05). Patients who had
      episodes of ischemia in spite of anti-ischemic therapy were at increased risk of
      all events studied. Heparin is more effective than inogatran in suppressing
      myocardial ischemia and clinical events at short-term follow-up. Continuous ST
      segment monitoring with vectorcardiography identifies nonresponders who are at an
      increased level of risk.

PMID- 9576151
TI  - Relation of heart rate variability and serum lipoproteins in type 1 diabetes
      mellitus and chronic stable angina pectoris.
AB  - This investigation examines whether serum lipoprotein levels in patients with
      diabetes mellitus and in those with coronary artery disease are associated with
      lower heart rate variability (HRV). The study group consisted of 58 subjects
      divided into 3 groups: normal subjects, chronic stable angina, and type 1
      diabetes. Twenty-four-hour ambulatory electrocardiographic recordings were
      analyzed in the time and frequency domains; standard instantaneous autonomic
      testing was also performed. On 24-hour ambulatory recordings, patients with
      chronic stable angina had significantly lower HRV than normals, and diabetics had
      a more marked reduction in HRV than both normals and anginal patients. When
      anginal patients and diabetics were stratified by total serum and low-density
      lipoprotein (LDL) cholesterol levels, diabetics with elevated total and LDL
      cholesterol had an additional, significant decrease in HRV parameters. No such
      difference was demonstrated in patients with stable angina. No significant
      correlations were noted for high-density lipoprotein (HDL) cholesterol,
      triglycerides, or total cholesterol/HDL ratio and HRV in diabetics or patient
      with angina. Diabetics with markedly abnormal peripheral reflexes had
      significantly higher triglycerides and total cholesterol/HDL ratios. Finally,
      standard tests of autonomic function did not correlate with total, LDL, HDL
      cholesterol levels, total cholesterol/HDL ratio, or triglycerides. Thus, we found
      a relation between atherogenic lipid levels and reduced HRV in diabetic patients
      that has not been previously identified.

PMID- 9576152
TI  - Circadian variation of the QT interval in patients with sudden cardiac death
      after myocardial infarction.
AB  - To evaluate the potential prognostic value of the circadian variation of QT
      intervals in predicting sudden cardiac death (SCD) in patients after myocardial
      infarction (MI), 15 pairs of post-MI patients (15 died suddenly within 1 year
      after MI [SCD victims] and 15 remained event-free [MI survivors]) were studied
      (mean age 60 +/- 8 years; 24 men and 6 women). The pairs were matched for age,
      gender, infarct site, presence of Q wave, left ventricular ejection fraction,
      thrombolytic and beta-blocker therapy. Fourteen normal subjects served as
      controls (mean age 55 +/- 9 years; 12 men). A 24-hour Holter electrocardiographic
      (ECG) recording was obtained from each subject. All recordings were analyzed
      using a Holter ECG analyser. QT, RR, and heart rate-corrected QT intervals (QTc)
      were automatically calculated by the analyzer, and hourly and 24-hour mean values
      of each measurement were derived from each recording. There was a pronounced
      circadian variation in the QT interval in parallel with the trend in the RR
      interval in normal subjects and in MI survivors. Circadian variation in both
      indexes was blunted in SCD victims. The QT interval was significantly longer at
      night than during the day in normal subjects (388 +/- 28 vs 355 +/- 21 ms, p =
      0.001) and in MI survivors (358 +/- 25 vs 346 +/- 15 ms, p = 0.008), but not in
      SCD victims (357 +/- 32 vs 350 +/- 31 ms, p = 0.6). The 24-hour mean value of the
      QT interval in SCD victims did not differ significantly from that in normal
      subjects or MI survivors. The QT interval at night was significantly shorter in
      SCD victims than in normal subjects (357 +/- 32 vs 388 +/- 28 ms, p = 0.02), but
      daytime values were similar. The QT interval in SCD victims did not differ
      significantly from that of MI survivors at any time. The QTc interval exhibited a
      small circadian variation in normal subjects. This variation was abolished in SCD
      victims and MI survivors. The 24-hour mean value of QTc was significantly longer
      in SCD victims than in normal subjects (424 +/- 25 vs 402 +/- 21 ms, p = 0.02),
      and in MI survivors (424 +/- 25 vs 404 +/- 32 ms, p < 0.05). The QTc interval of
      SCD victims differed from that of normal subjects during both the day (421 +/- 25
      vs 400 +/- 17 ms, p = 0.02) and night (424 +/- 26 vs 403 +/- 23 ms, p = 0.03).
      Thus, blunted circadian variation in QT intervals, abolished circadian variation
      in QTc intervals, and prolonged QTc intervals may suggest an increased risk of
      SCD in patients after MI.

PMID- 9576153
TI  - Comparison of primary coronary stenting to primary balloon angioplasty with stent
      bailout for the treatment of patients with acute myocardial infarction.
AB  - This study compares the immediate and long-term outcomes of a primary coronary
      stenting strategy with primary balloon angioplasty with stent bailout in the
      treatment of patients with acute myocardial infarction (AMI). One hundred forty
      seven consecutive patients who underwent primary balloon angioplasty with stent
      bailout (n = 94) or primary stenting (n = 53) for AMI were clinically followed
      for 8.1 +/- 5.7 and 8.5 +/- 4.5 months, respectively. Immediate results, as well
      as in-hospital and long-term ischemic events (death, reinfarction, and repeat
      revascularization) were compared between both groups. Angiographic success was
      91.5% in the balloon angioplasty group and 94% in the stent group. In-hospital
      and late follow-up combined ischemic events were 22 of 94 (23%) versus 0 of 53
      (0%); p < 0.001 and 33 of 78 (42%) versus 13 of 53 (25%), p = 0.04 for the
      balloon angioplasty and stent groups, respectively. At 6 months, the cumulative
      probability of repeat target lesion revascularization was higher in the balloon
      angioplasty group (47% vs 18%, p = 0.0006) as was the probability of late target
      revascularization (36% vs 18%, p = 0.046); the cumulative event-free survival
      after 6 months was significantly lower in the balloon angioplasty group (44% vs
      80%, p = 0.0001). This study demonstrates that a primary stent placement strategy
      in patients with AMI is safe, feasible, and superior to primary balloon
      angioplasty with stent bailout. Primary stenting results in a larger
      postprocedural minimal luminal diameter, a lower early and late recurrent
      ischemic event rate, and a lower incidence of target lesion revascularization at
      follow-up.

PMID- 9576154
TI  - Correct utilization of exercise electrocardiographic leads in differentiation of
      men with coronary artery disease from patients with a low likelihood of coronary
      artery disease using peak exercise ST-segment depression.
AB  - In this study we compared the diagnostic characteristics of the individual
      exercise electrocardiographic leads, 3 different lead sets comprising standard
      leads and the effect of the partition value in the detection of coronary artery
      disease (CAD). The diagnostic variable used was ST-segment depression at peak
      exercise, and the study population consisted of 101 patients with CAD and 100
      patients with a low likelihood of the disease. The lead system used was the Mason
      Likar modification of the standard 12-lead system and exercise tests were
      performed on a bicycle ergometer. The comparisons were performed by means of
      receiver-operating characteristic analysis and by determining sensitivities at a
      fixed 95% specificity. These properties, defined here as diagnostic capacity,
      were the most efficacious in leads I, -aVR, V4, V5, and V6. Diagnostic capacities
      in leads aVL, aVF, III, V1, and V2 were quite poor; statistical comparisons
      indicated significant differences between these leads and lead V5 (p < or =
      0.0001 in each case). Use of the maximum value of ST-segment depression at peak
      exercise derived from all 12 leads produced a considerable decrease in the
      diagnostic capacity of the exercise electrocardiogram compared with lead V5. The
      exclusion of leads aVL, V1, and III improved the diagnostic capacity compared
      with the 12-lead set, but it was still smaller than that of lead V5. With use of
      a lead set with the 5 best leads increased the diagnostic capacity over other
      lead sets and over any individual lead. Further improvement was noted when a 50%
      smaller partition value was applied to leads I and -aVR than for the other leads
      (p = 0.041). In conclusion, this study suggests that use of leads I, -aVR, V4,
      V5, and V6 is the most influential when differentiating between patients with CAD
      and patients with a low likelihood of disease using peak exercise ST-segment
      depression. The effective use of leads I and -aVR requires the partition value
      applied for these leads to be 50% smaller than that used for the lateral
      precordial leads.

PMID- 9576155
TI  - A randomized trial of vascular hemostasis techniques to reduce femoral vascular
      complications after coronary intervention.
AB  - This report details a prospectively randomized clinical trial comparing
      mechanical clamp compression to hand applied pressure for attaining vascular
      hemostasis after coronary intervention. Effectiveness was determined by comparing
      the incidence of femoral vascular complications resulting from each of the 2
      techniques. Eligible participants included 778 consecutive patients scheduled for
      percutaneous coronary intervention over an 8-month period. An unselected cohort
      of the eligible patients (n = 592), determined by the availability of cross
      trained clinicians, underwent follow-up serial physical examinations by blinded
      observers for the duration of their hospital stay. A second, similarly determined
      cohort (n = 390), underwent color-duplex ultrasonography within 24 hours of
      sheath removal. Baseline demographic and clinical characteristics, sheath removal
      parameters, and subsequent outcomes were collected prospectively. The primary end
      point was a composite of ultrasound-defined femoral vascular complications:
      femoral artery thrombosis, echogenic hematoma, pseudoaneurysm, or arteriovenous
      fistulae formation. Complications diagnosed by physical examination constituted
      the second fundamental end point and included: persistent oozing, ecchymosis,
      hematoma, bruit, and pulsatile mass. Compared to manual compression, mechanical
      clamp hemostasis reduced the primary adverse end point by 63% (p = 0.041).
      Physical examination detected ecchymosis, oozing, and hematomas at equally high
      frequencies in the two cohorts. Although 65% of the patients in both treatment
      groups encountered at least one of these cosmetic complications, the diagnoses
      made by physical examination did not correlate with ultrasound-defined pathology.
      Multivariable stepwise logistic regression analysis identified a relationship of
      advanced age and lower body weight to vascular complications. Utilization of a
      mechanical clamp rather than conventional hand pressure to attain vascular
      hemostasis significantly reduces ultrasound-defined femoral vascular pathology.
      Discrepancies between physical examination and ultrasound diagnoses challenge the
      utility of clinical assessment alone and establish ultrasound as the diagnostic
      modality of choice.

PMID- 9576156
TI  - Intravascular ultrasound evaluation of plaque distribution at curved coronary
      segments.
AB  - Although the distribution of atherosclerosis at the curved coronary segments has
      implications for atherogenesis and interventional procedures, few data exist
      regarding the plaque distribution in these sites. Therefore, we prospectively
      analyzed the intravascular ultrasound images of 55 coronary sites from 37
      patients where the atherosclerotic plaque and pericardium were simultaneously
      demonstrated by intravascular ultrasound. The pericardial images were defined as
      a high-intensity linear echo image moving during cardiac cycles outside the
      vessel wall. By the line that was parallel to the pericardial image, the vessel
      area was divided into 2 semicircles with the same area, namely myocardial and
      pericardial sides. In each side, the maximal thickness, area, and percent area of
      plaque were measured. The plaque thickness and area of the myocardial side were
      significantly greater (1.5 +/- 0.5 mm, 4.9 +/- 2.1 mm or 66%, mean +/- SD) than
      those of the pericardial side (1.1 +/- 0.4 mm, 3.5 +/- 2.1 mm2 or 45%, p < 0.01).
      The maximal plaque thickness was positioned at the point with a mean angle of 139
      +/- 37 degrees from the point just facing the pericardial image, indicating that
      atherosclerosis was eccentrically located on the opposite side of the pericardium
      in these coronary segments, and suggesting that the side of the pericardial image
      represents the outer curvature of the coronary artery. These results indicate
      that the pericardial images can be seen by intravascular ultrasound, facilitating
      the recognition of the disease distribution in situ. The eccentric plaque located
      on the inner wall at the curved coronary segments, probably due to uneven local
      shear stress, may have implications for the interventional procedures for these
      segments.

PMID- 9576157
TI  - Impact of race and age on the effects of regionalization of cardiac procedures in
      the Department of Veterans Affairs Health Care System.
AB  - Previous studies have demonstrated that regionalization of resources for cardiac
      catheterization, percutaneous coronary artery angioplasty (PTCA), and coronary
      artery bypass graft surgery (CABG) reduces the rate of procedure use. It was
      hypothesized that the impact of regionalization would be greater for the elderly
      and for African-Americans than for other populations. Discharge medical records
      of 30,901 patients admitted to a Veterans Affairs (VA) medical center between
      October 1, 1993, and September 30, 1994, with a diagnosis of coronary artery
      disease were analyzed. The presence of a cardiac catheterization laboratory in
      the patients' local VA facility significantly increased the likelihood of
      undergoing catheterization, PTCA, and CABG, as determined by odds ratios and
      associated confidence limits estimated by logistic regression techniques. The
      presence of a cardiac surgical facility also significantly increased the
      likelihood of having the procedures. The odds ratios estimating the effects of
      resource availability were significantly greater for the subgroup of patients
      aged > or =70 years than for the younger subgroup for catheterization, PTCA, and
      CABG and for African-Americans than for white patients for PTCA and CABG. Thus,
      within the VA health care system, regionalization of cardiac procedures has a
      significant impact on utilization rates of tertiary cardiac procedures. These
      differences are significantly greater for the elderly and for African-Americans
      than for the general population.

PMID- 9576158
TI  - Cardiovascular events and mortality in newly and chronically depressed persons >
      70 years of age.
AB  - The role of duration of depressed mood in the prediction of cardiovascular
      disease (CVD) requires further study, as it has been suggested that emerging
      depressive symptoms may be a better predictor than persistent depressive
      symptoms. This prospective cohort study of 3,701 men and women aged > 70 years
      uses 3 measurement occasions of depressive symptomatology (Center for
      Epidemiologic Studies-Depression Scale) during a 6-year period to distinguish
      persons who were newly (depressed at baseline but not at 3 and 6 years before
      baseline) and chronically depressed (depressed at baseline and at 3 or 6 years
      before baseline). Their risk of subsequent CVD events and all-cause mortality was
      compared with that of subjects who were never depressed during the 6-year period.
      Outcome events were based on death certificates and Medicare hospitalization
      records. During a median follow-up of 4.0 years, there were 732 deaths
      (46.2/1,000 person-years) and 933 new CVD events (64.7/1,000 person-years). In
      men, but not in women, newly depressed mood was associated with an increased risk
      of CVD mortality (relative risk 1.75, 95% confidence interval [CI] 1.00 to 3.05),
      new CVD events (relative risk 2.07, 95% CI 1.44 to 2.96), and new coronary heart
      disease events (relative risk 2.03, 95% CI 1.28 to 3.24) after adjustment for
      traditional CVD risk factors. The association between newly depressed mood and
      all-cause mortality was smaller (relative risk 1.40, 95% CI 0.95 to 2.07).
      Chronic depressed mood was not associated with new CVD events or all-cause
      mortality. Our findings suggest that newly depressed older men, but not women,
      were approximately twice as likely to have a CVD event than those who were never
      depressed. In men, recent onset of depressed mood is a better predictor of CVD
      than long-term depressed mood.

PMID- 9576159
TI  - Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic
      atrial fibrillation.
AB  - To compare the safety and efficacy of amiodarone and sotalol in the treatment of
      patients with recurrent symptomatic atrial fibrillation (AF), 70 patients were
      entered into a randomized, double-blind study. Of these, 35 received amiodarone
      and 35 sotalol. There were no significant differences in baseline clinical
      characteristics between groups. Patients with ejection fraction < 40% or
      clinically significant heart disease were excluded. Patients randomized to
      amiodarone began with 800 to 1,600 mg/day for 7 to 14 days orally. After the
      initial loading phase, the drug dose was tapered to maintenance levels over 7 to
      12 days; thereafter, therapy was generally maintained at a dosage of 200 mg/day.
      The sotalol dosage was 80 to 360 mg twice daily, as tolerated. Follow-up clinical
      evaluations were conducted at 1, 2, 4, 6, 9, and 12 months. The proportion of
      patients remaining in sinus rhythm on each agent was calculated for the 2 groups
      using the Kaplan-Meier method. Ten of the 35 patients who were taking amiodarone
      developed AF during the 12-month observation period, compared with 21 of the 35
      who were taking sotalol (p = 0.008). No significant effect of sex, age, left
      atrial size, or type of AF could be detected that increased the risk of
      development of AF. We conclude that both amiodarone and sotalol can be used for
      the maintenance of normal sinus rhythm in patients with recurrent symptomatic AF
      but that amiodarone is the more effective of the 2 drugs for this purpose.

PMID- 9576160
TI  - Late outcome of survivors of idiopathic ventricular fibrillation.
AB  - This report describes clinical, hemodynamic, and electrophysiologic
      characteristics of 18 consecutive survivors of sudden cardiac arrest due to
      idiopathic ventricular fibrillation (VF) between 1986 and 1996. Long-term data in
      relation to the prescribed therapy are presented. The mean age of the 18 patients
      was 48 +/- 14 years (median 49). Electrophysiologic studies showed a low
      inducibility of sustained ventricular tachyarrhythmias in 4 patients (22%).
      Treatment consisted of class III agents, beta blockers, or implantable
      cardioverter-defibrillators. Two patients were discharged without any therapy.
      Therapy control was undertaken either by serial drug testing or by the empirical
      approach. Serious complications of therapy occurred in 2 patients: 1 patient
      experienced a proarrhythmic effect of antiarrhythmic drug therapy, and the other
      patient received multiple inadequate defibrillator discharges due to a defect in
      the transvenous lead. All but 1 patient (94%) remained free of recurrences of
      sudden cardiac arrest during a follow-up time of 45 +/- 29 months (median 41).
      One patient died 2 weeks after surviving cardiac arrest due to intractable VF
      while receiving sotalol treatment. Therapy guided by electrophysiologic studies
      did not have any impact on survival. Adverse effects or noncompliance led to
      discontinuation of drug therapy in 7 patients after a mean period of 31 +/- 30
      months. Without any treatment 9 patients remained without recurrences over 45 +/-
      33 months. Because of the absence of risk factors for arrhythmia recurrence and
      criteria to select therapy, randomized prospective studies are warranted to
      assess the optimal therapies in these young, ostensibly healthy patients.

PMID- 9576161
TI  - Comparative accuracy of three automated techniques in the noninvasive estimation
      of central blood pressure in men.
AB  - Automated devices have regularly replaced manual sphygmomanometry for the
      determination of blood pressure not only in homes and clinics, but also in
      emergency and critical care settings. Few studies exist that correctly assess the
      accuracy of these devices, and even fewer that specifically compare commercially
      available units that rely on different physiologic events for measurement. Six
      hundred pressure measurements were obtained from 120 subjects using 1 of 3
      randomly selected blood pressure monitors. In addition, central arterial pressure
      measurements were obtained simultaneously and directly from the ascending aorta
      of each subject. Overall, these devices tended to overestimate diastolic (+2.5 mm
      Hg, p < 0.0001) and mean (+3.8 mm Hg, p < 0.0001) pressures, but not systolic
      (+0.7 mm Hg, p = NS) pressure. Compared with the other 2 devices, device I,
      relying on oscillometric detection, demonstrated a significantly smaller mean
      absolute error for diastolic pressure (4.9 +/- 3.0 vs 7.0 +/- 4.8 and 6.2 +/- 5.3
      mm Hg, p < 0.0001) and mean pressure (4.0 +/- 3.2 vs 7.8 +/- 5.9 and 8.6 +/- 7.5
      mm Hg, p < 0.0001), and a trend toward smaller error with systolic pressure (6.8
      +/- 6.5 vs 7.3 +/- 6.8 and 8.0 +/-5.6 mm Hg, p = 0.19). Clinically significant
      (+/-10 mm Hg) errors were common with each device (24.8% overall), but serious
      (+/-20 mm Hg) errors were unusual (3.2%) and did not occur at all with device I
      during diastolic and mean pressure measurement. All of the devices tested could
      be expected to perform satisfactorily in most clinical settings provided that an
      average error of 4.0 to 8.6 mm Hg is tolerable. This level of accuracy typically
      extended throughout the range of pressures anticipated in most noncritical
      clinical situations. As implemented in the devices tested, noninvasive
      measurement by oscillometry with stepped deflation is more accurate than
      automated auscultation.

PMID- 9576162
TI  - Long-term follow-up of rheumatic patients undergoing left-sided valve replacement
      with tricuspid annuloplasty--validity of preoperative echocardiographic criteria
      in the decision to perform tricuspid annuloplasty.
AB  - Between September 1989 and December 1991, modified De Vega tricuspid annuloplasty
      was performed in 43 patients who survived surgery for mitral or mitral plus
      aortic valve replacement. The preoperative indications for tricuspid annuloplasty
      were moderate to severe tricuspid regurgitation (TR) in 33 patients and mild or
      no TR but with a dilated tricuspid annulus (> or =30 mm) as measured by 2
      dimensional echocardiography at end-diastole in 10 patients. The mean age was 31
      +/- 13 years. The mean duration of follow-up was 57 +/- 18 months. Overall long
      term mortality was 12%. On Doppler color flow mapping, postoperative severe TR
      was present in 1 patient and moderate TR in 4 patients at latest follow-up. The
      tricuspid annulus diameter decreased from 37 +/- 5 mm preoperatively to 24 +/- 6
      mm at latest follow-up. During the study period, an additional 77 patients
      underwent mitral valve replacement or double valve replacement, but without
      tricuspid annuloplasty. Within this group, 38 patients had a preoperative
      tricuspid annulus diameter of > or =30 mm, and 5 of these patients (13%)
      developed moderate or severe TR in the postoperative period, which may have been
      prevented had clinicians adhered to the preoperative indications for tricuspid
      annuloplasty. Thus, preoperative echocardiographically documented moderate or
      severe TR or a tricuspid annulus diameter of > or =30 mm are valid indications
      for performing tricuspid annuloplasty; modified De Vega tricuspid annuloplasty is
      a durable procedure in rheumatic patients; it appears that reducing the diastolic
      tricuspid annulus diameter to 24 mm is adequate to prevent residual TR in the
      long term.

PMID- 9576163
TI  - Influence of myocardial infarction, coronary artery bypass surgery, and stroke on
      cognitive impairment in late life.
AB  - Relations between cognitive test scores in later life and prior myocardial
      infarction (MI), coronary artery bypass graft surgery (CABG), and stroke were
      examined for this study. Subjects were 3,734 Japanese-American men (80% of
      surviving Honolulu Heart Program cohort) aged 71 to 93 years at the time of
      cognitive testing. Impairment was defined as scoring below the 16th percentile on
      a validated cognitive assessment scale. Prior MI, stroke, and CABG were
      established using hospital surveillance, history, and record review. After
      adjustment for age, years of education, and years of childhood spent in Japan,
      men with prior stroke were significantly more likely than others to have poor
      cognitive performance (odds ratio 4.4, 95% confidence limits 3.0 to 6.7). History
      of > 1 stroke was associated with an odds ratio of 50 (95% confidence limits 10.5
      to 238.3). There was no significant association between cognitive performance and
      > or = 1 prior MI or history of CABG. Time between events and cognitive function
      testing did not affect results. Analyses support a significant association
      between clinical stroke and persistent cognitive impairment, but fail to
      implicate CABG or MI.

PMID- 9576164
TI  - Midazolam premedication improves tolerance of transesophageal echocardiography.
AB  - Patient premedication for transesophageal echocardiography (TEE) is still under
      debate, especially the use of sedatives. We performed a double-blind, placebo
      controlled study to clarify the efficacy of low-dose intravenous midazolam as
      premedication for TEE. Placebo or midazolam (< or =50 kg, 2.0 mg intravenously;
      50 to 80 kg, 2.5 mg; and > or =80 kg, 3.0 mg intravenously) was given in addition
      to topical anesthesia to 200 consecutive in- and outpatients. Blood pressure,
      heart rate, and oxygen saturation were monitored. Patients were interviewed
      immediately, and 2 to 10 days after TEE. Sixteen patients received an additional
      dose of midazolam, and in 12 follow-up was incomplete. Patients taking midazolam
      reported less gag reflex at probe introduction and during TEE, as did the
      examiners (p < 0.05 to 0.0001). Probe manipulations were found to produce less
      discomfort after midazolam administration (p < 0.005). Midazolam patients
      experienced less dyspnea (p < 0.01) despite a minimal decrease in oxygen
      saturation of 2% (p < 0.0001). The following day patients taking midazolam
      reported less sore throats, and painful swallowing was less frequent (p < 0.01 to
      0.001). Systolic blood pressure decreased slightly in the midazolam group (132 +/
      24 to 121 +/- 20 mm Hg, p < 0.0001). The rate of minor complications showed no
      difference. Thus, TEE probe introduction and manipulation was tolerated better
      after low-dose midazolam premedication, and patients experienced less pharyngeal
      discomfort the day after. Midazolam was well tolerated and the complication rate
      did not increase. Thus low-dose, short-acting benzodiazepine premedication
      improves patient comfort during and after TEE and generous use can be
      recommended.

PMID- 9576165
TI  - John Webster Kirklin, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 9576166
TI  - On the statins, correcting plasma lipid levels, and preventing the clinical
      sequelae of atherosclerotic coronary heart disease.
AB  - The statins correct plasma lipid levels optimally, yet the real magnitude of
      their benefits is marginal and certainly not better than attained with agents
      that do not affect plasma lipid levels. It is suggested that some of our
      recommendations and actions relating to plasma cholesterol levels and to
      atherosclerosis are based on concepts that are fundamentally flawed and need to
      be revised.

PMID- 9576168
TI  - Do stress echocardiography and myocardial perfusion imaging have the same ability
      to identify the low-risk patient with known or suspected coronary artery disease?
AB  - Although both stress myocardial perfusion imaging and echocardiography may have
      significant prognostic value, the annual death/myocardial infarction rate appears
      to be much higher in patients with a negative stress echocardiogram. This may
      greatly limit its ability to act as a "gatekeeper" for additional invasive and
      interventional procedures.

PMID- 9576167
TI  - The worth of controlling plasma lipids.
AB  - The worth of controlling plasma lipids is well established; clearly, it is better
      to prevent atherosclerosis than wait to treat it after it has reached an advanced
      stage.

PMID- 9576169
TI  - Two-year follow-up in pediatric and adult patients with single-pass lead VDD
      pacing system.
AB  - VDD pacing follow-up is similar in pediatric and adult patients. Atrial and
      ventricular pacing parameters are stable during 2-year follow-up in children, and
      single-pass lead VDD pacing is recommended when the sinus node function is
      normal.

PMID- 9576170
TI  - Influence of altered loading conditions on left atrial appendage function in
      vivo.
AB  - This study sought to examine the influence of heart failure treatment on left
      atrial (LA) appendage function in 10 patients with left ventricular dysfunction.
      After treatment of heart failure, LA appendage function markedly improved, less
      dependent on LA and left ventricular functions, which suggests that with altered
      loading conditions, LA appendage function changes chiefly through its intrinsic
      contractile property.

PMID- 9576171
TI  - Normal fetal cardiac dimensions obtained by perpendicular imaging.
AB  - This study provides normal fetal cardiac dimensional data in a large patient
      group over a wide range of gestational ages. Perpendicular imaging decreased
      lateral resolution error, resulting in normal values with narrower confidence
      limits than in prior studies.

PMID- 9576172
TI  - Size of ventricular structures influences surgical outcome in Down syndrome
      infants with atrioventricular septal defect.
AB  - To evaluate the relation between ventricular structure size and surgical outcome
      in Down versus non-Down syndrome infants with an atrioventricular septal defect,
      we reviewed the charts and echocardiograms of 44 consecutive infants (34 with
      Down syndrome) who underwent atrioventricular septal defect repair. Children with
      Down syndrome had significantly greater aortic valve diameters, left ventricular
      valve areas, and left/right atrioventricular valve area ratios as well as fewer
      adverse outcomes than non-Down syndrome children.

PMID- 9576173
TI  - Additional ST-segment elevation after reperfusion: a beneficial sign in patients
      with acute myocardial infarction?

PMID- 9576174
TI  - The protease-activated receptors and their cellular expression and function in
      blood-related cells.

PMID- 9576175
TI  - Lack of sequence variations in the C4b-BP beta-chain in patients with type III
      protein S deficiency bearing the Ser 460 to Pro mutation: description of two new
      intragenic isomorphisms in the C4b-BP beta-chain gene (C4BPB).
AB  - Type III protein S (PS) deficiency, characterized by low levels of free PS and
      normal total PS levels, is often associated with the Ser 460 to Pro substitution.
      However, some patients bearing this mutation have normal PS levels, suggesting
      that another gene defect may account for this phenotype. We postulated that this
      defect was located in the C4b-BP beta-chain gene (C4BPB) and searched for a
      mutation in the coding regions of this gene in 35 propositi with type III PS
      deficiency and bearing the Ser 460 to Pro mutation. No mutations explaining the
      phenotype of type III PS deficiency were identified. We did, however, find two
      frequent nucleotide changes, one being located in the donor splice site of intron
      d and the second in the codon corresponding to Asn 137. We used these two
      polymorphisms to establish C4BPB gene haplotype in five informative type III PS
      deficient families and exclude a role of the C4BPB gene in this phenotype of
      three of them. Finally, increased C4b-BP beta-chain levels were not responsible
      for the phenotype of type III PS deficiency as the C4BPB haplotype did not
      correlate with C4b-BP beta-chain levels.

PMID- 9576176
TI  - Humic acid reduces protein-C-activating cofactor activity of thrombomodulin of
      human umbilical vein endothelial cells.
AB  - Humic acid in the drinking water of blackfoot disease endemic areas in Taiwan has
      been implicated as one of the aetiological factors of the disease. For this
      report we examined the effects of humic acid on the expression of thrombomodulin
      (TM) cofactor activity by cultured human umbilical vein endothelial cells
      (HUVEC). Incubation of HUVEC with humic acid (HA) isolated from the drinking
      water, as a synthetic humic acid polymer (SHA) or with commercial HA, resulted in
      a dose-dependent reduction of cell surface thrombomodulin activity.
      Characterization of the mechanism by which humic acid reduced the protein C
      activation indicated that inhibition was not caused by production or release of a
      protein C inhibitor. Kinetic analysis showed that binding affinities of TM to
      thrombin and of TM-thrombin complex to protein C was unchanged upon humic acid
      treatment. However, the cell surface TM activity was reduced by humic acid, which
      functions as an irreversible noncompetitive inhibitor of thrombin binding. Down
      regulation of TM was inhibited by non-selective protein kinase C inhibitors and a
      selective inhibitor. These results suggest that protein kinase C is intricately
      involved in HA-induced TM down-regulation. Down-regulation of TM was also
      inhibited by free radical scavengers. All these changes occurred in the absence
      of significant cytotoxic effect. In conclusion, our results suggest that HA
      induces down-regulation of TM by directly increasing permeability of the cell
      membrane, thus causing elevation in [Ca2+]i. This species functions as a second
      messenger to activate protein kinase C, and/or Ca-dependent enzymes eventually
      inducing down-regulation of TM. Attenuation of vascular endothelial cell TM
      cofactor activity by humic acid may play a role in the humic acid-induced
      thrombotic vascular disorders of blackfoot disease.

PMID- 9576177
TI  - Electrospray ionization mass spectrometry identification of fibrinogen Banks
      Peninsula (gamma280Tyr-->Cys): a new variant with defective polymerization.
AB  - Fibrinogen Banks Peninsula was identified in the mother of a patient referred for
      investigation following recurrent epistaxis. Coagulation tests revealed prolonged
      thrombin and reptilase times and a decreased functional fibrinogen level.
      Thrombin-catalysed release of fibrinopeptides A and B was normal, and no
      abnormalities were detected by DNA sequencing of the regions encoding the
      thrombin cleavage sites in the Aalpha and Bbeta genes. Reducing SDS-PAGE and
      reverse-phase HPLC analysis of purified fibrinogen chains were normal, as was
      electrospray ionization mass spectrometry (ESI-MS) analysis of isolated Aalpha
      and Bbeta chains. However ESI-MS revealed a mass of 48345 D for the isolated
      gamma chains, 31 D less than the measured mass of control chains (48376 D). Since
      normal and abnormal gamma chains were not resolved, this implies a 60-62 D mass
      decrease in 50% of the molecules. A 60 D decrease was confirmed when DNA
      sequencing indicated heterozygosity for a mutation of Tyr-->Cys at codon 280 of
      the gamma chain gene. Fibrin monomer polymerization revealed a delayed lag phase
      and reduced final turbidity and although factor XIIIa crosslinking of fibrinogen
      was normal, it is likely that this delay is due to impaired D:D self association.
      Recent crystallographic studies show residues gamma280 and gamma275 make contact
      across the D:D interface, suggesting a similar mechanism for the polymerization
      defects in fibrinogens Banks Peninsula and Tokyo II (gamma275Arg-->Cys).

PMID- 9576178
TI  - Severe coagulation factor V deficiency caused by a 4 bp deletion in the factor V
      gene.
AB  - Factor V (FV) deficiency (parahaemophilia) is an autosomal recessive bleeding
      disorder with an incidence of 1:10(6). We have studied a young girl with very
      mild bleeding symptoms and undetectable levels of plasma factor V antigen and
      activity (<0.3% and <1.6% of normal, respectively). Both parents showed plasma
      levels of factor V activity of about 50% of normal. Sequence analysis of the 5'-
      and 3'-untranslated, coding and adjacent regions of the factor V gene revealed
      the presence of a 4 bp deletion in exon 13. Subsequent screening of members of
      the family for the mutation showed that both parents were heterozygous for the
      mutation, that one healthy sister carried only normal alleles, and that the
      patient was homozygous for the mutated allele. The mutation introduced a
      frameshift and a novel premature stop codon in codon 1303, and would predict the
      synthesis of a truncated factor V molecule that lacks part of the B domain and
      the complete light chain. However, no factor V heavy chain could be detected in
      the plasma of the patient. Furthermore, factor V activity could not be detected
      in the patients' platelets. This is the first reported mutation in the factor V
      gene that predicts a type I quantitative factor V deficiency. Surprisingly, the
      patient, who is homozygous for the mutation, so far has only a very mild bleeding
      tendency.

PMID- 9576179
TI  - Direct activation of factor X by monocytes occurs during cardiopulmonary bypass.
AB  - We hypothesized that monocyte procoagulant activity, which includes up-regulation
      of tissue factor and direct activation of factor X by CD11b. is an activator of
      coagulation during cardiopulmonary bypass (CPB), because recent studies have cast
      doubt on the presumption that the surfaces of CPB activate the intrinsic pathway.
      Sequential samples were taken from 17 patients undergoing cardiac surgery. During
      CPB a significant increase in thrombin-antithrombin complexes occurred (P <
      0.0005). Factor XIIa levels increased (P < 0.005) but remained within the normal
      range. Total monocyte procoagulant activity was measured and a functional assay
      was developed to detect direct activation of factor X alone. There was a
      significant increase in total procoagulant activity on circulating monocytes from
      the start of CPB (P < 0.005) to which direct factor X activation was a major
      contributor (P < 0.005). Direct activation of factor X was inhibited by CD11b
      blocking peptides. Using flow cytometry, up-regulation of monocyte CD11b (P <
      0.0005). but not up-regulation of tissue factor, was found on circulating
      monocytes. Monocytes adherent on the oxygenator fibres showed increased CD11b
      expression (P < 0.0001), but no tissue factor when assessed by fluorescent image
      analysis. In conclusion, direct activation of factor X through monocyte CD11b
      occurs during CPB and appears to contribute to thrombin generation during CPB.

PMID- 9576180
TI  - Factor VII Morioka (FVII L-26P): a homozygous missense mutation in the signal
      sequence identified in a patient with factor VII deficiency.
AB  - We investigated the molecular basis of factor VII deficiency in a Japanese
      patient and identified a novel missense mutation in the signal sequence of the
      gene. Factor VII activity and antigen level measured in the patient were 10.7%
      and 11% of normal, respectively. All exons except 1B and the 5'-flanking region
      containing promoter region were amplified by polymerase chain reaction (PCR) from
      genomic DNA. Sequencing analysis of the PCR fragments revealed that the patient
      was a homozygote for a T to C substitution at nucleotide position 38. This
      mutation predicts an amino acid replacement of leucine to proline at codon -26 in
      the hydrophobic core of the signal peptide, which probably affects translocation
      of the protein into endoplasmic reticulum and subsequently causes reduction in
      plasma factor VII level.

PMID- 9576181
TI  - Impaired redistribution of aminophospholipids with distinctive cell shape change
      during Ca2+-induced activation of platelets from a patient with Scott syndrome.
AB  - We have investigated phospholipid redistribution, membrane vesicle shedding,
      shape change, and granule release following A23187 activation of platelets from a
      patient with Scott syndrome, characterized by impaired transmembrane migration of
      phosphatidylserine (PS) accompanied by haemorrhagic complications, and two of her
      children. Electron spin resonance spectroscopy measurement of phospholipids
      redistribution showed that the internalization of PS was unaffected by the
      disorder but, after activation, PS exposure was significantly reduced in
      platelets from the homozygous-type patient. Vesicle shedding was also reduced in
      these platelets. However, the slow redistribution of phosphatidylcholine was
      similar to that observed in normal platelets. When treated with calpeptin,
      platelets from the homozygous-type patient, unlike normal or heterozygous Scott
      syndrome platelets, showed a smoothly rounded shape without filopods after
      activation. Following A23187 activation of normal platelets, filopod formation
      was consecutive to the re-exposition of aminophospholipids on the outer leaflet
      of the plasma membrane, and the existence of a floppase (outward aminoPLs
      translocase) has been suggested. In homozygous Scott syndrome platelets the
      deficiency in PS re-exposition, the absence of filopod formation, and low vesicle
      shedding are correlated with each other, and argue in favour of a disruption of
      the proposed floppase activity.

PMID- 9576182
TI  - Characterization of the thromboxane synthase pathway product 12-oxoheptadeca-5(Z)
      8(E)-10(E)-trienoic acid as a thromboxane A2 receptor antagonist with minimal
      intrinsic activity.
AB  - Thromboxane synthase forms thromboxane (TX) A2 and 12(S)-hydroxyheptadeca-5(Z)
      8(E)-10(E)-trienoic acid (HHT) at equimolar amounts. Twelve-oxoheptadeca-5(Z)
      8(E)-10(E)-trienoic acid (Oxo-HT) is the primary metabolite of HHT and has been
      described to be an inhibitor of platelet aggregation. Functional studies, Schild
      analysis and competitive binding studies were performed to clarify its mode of
      action. Oxo-HT was prepared biosynthetically as well as chemosynthetically,
      purified and characterized by gas chromatography and mass spectrometry. Platelet
      activation was assessed by determination of shape change, aggregation, fibrinogen
      binding and P-selectin expression using optical aggregometry and flow cytometry.
      Oxo-HT 0.1 nM to 50 microM did not induce platelet activation. Furthermore, it
      had no effect on platelet activation induced by thrombin, ADP or PAF. In
      contrast, Oxo-HT inhibited platelet aggregation, fibrinogen binding and P
      selectin expression induced by U46619 in a competitive manner. Schild analysis
      for U146619-induced fibrinogen binding and P-selectin expression revealed pA2
      values of 6.1 and 6.6, respectively, which correspond to Kd values of
      approximately 0.8 microM and 0.3 microM, respectively. Oxo-HT also inhibited
      U46619 induced shape change (IC50 is approximately equal to 10 microM). However,
      Oxo-HT over a concentration range of 0.1-1 microM enhanced the partial shape
      change induced by low concentrations of U46619. Thus Oxo-HT seems to possess a
      minimal agonistic potential, which alone is not sufficient to trigger a platelet
      activation but can enhance low levels of platelet activation. Oxo-HT blocked the
      binding of [3H]SQ 29548 in a concentration-dependent manner, whereas HHT did not
      displace [3H]SQ 29548. The Kd of Oxo-HT determined from competition binding
      studies was 7.7 microM, about 10-25-fold higher than the apparent Kd determined
      by Schild analysis. This discrepancy might be due to a desensitization of the
      TXA2 receptor triggered by the minimal intrinsic activity of Oxo-HT. We conclude
      that Oxo-HT is a naturally occurring specific TXA2 receptor antagonist with
      minimal intrinsic activity. Oxo-HT may contribute to the regulation of TXA2
      induced platelet activation in vivo.

PMID- 9576183
TI  - Rapid heterozygote detection in Glanzmann's thrombasthenia.
AB  - To assess the potential of using flow cytometric analysis of platelet
      glycoprotein IIb in the detection of heterozygotes in Glanzmann's thrombasthenia
      (GT) we compared the fluorescence intensity of anti-CD41-labelled platelets of
      obligatory heterozygotes with that of normal subjects. This study showed that
      normal subjects had relative fluorescences occasionally overlapping with
      heterozygotes. Use of an independent factor, the mean platelet volume, as a
      correction factor for platelet size differences eliminated this overlap. This
      study indicates that it is possible to confidently and rapidly predict the
      carrier status of family members of GT sufferers, both type I and type II, by
      flow cytometric means.

PMID- 9576184
TI  - The Platelet Function Analyzer (PFA-100): a novel in-vitro system for evaluation
      of primary haemostasis in children.
AB  - The PFA-100 system provides an in-vitro method of assessing primary platelet
      related haemostasis by measuring the time (the closure time, or CT) taken for a
      platelet plug to occlude a microscopic aperture cut into a membrane coated with
      collagen and either epinephrine or ADP. We used the system to establish normal
      ranges for CTs in healthy children, adults and neonates. Mean CTs of healthy
      children were independent of the needle gauge used (21G or 23CG) for blood
      sampling; they were very similar to the mean CTs of healthy adults, but longer
      than mean CTs of healthy neonates. Although children with haemophilia had normal
      CTs, the PFA-100 system was found to be potentially useful in screening for von
      Willebrand disease in children.

PMID- 9576185
TI  - CD3-CD4-CD8-CD56-CD19-CD14- cells and CD3+CD8 dull-positive cells produce IL-4 in
      AIDS patients.
AB  - We used flow cytometry to identify the presence of intracellular cytokines
      (cytoflow) and analyse the production of IL-4 in peripheral blood from AIDS
      patients who have practically no CD4+ T cells. We found that IL-4 was produced by
      CD3-CD4-CD8-CD56-CD19-CD14- cells and CD3+CD8 dull-positive cells in AIDS
      patients. Moreover, CD3-CD4-CD8-CD56-CD19-CD14- cells had helper activity for
      immunoglobulin synthesis. These findings indicate that instead of CD4+ T helper
      cells, C3-CD4-CD8-CD56-CD19-CD14- cells and CD3+CD8 dull-positive cells may be an
      important source of IL-4 in a variety of immune responses for AIDS patients.

PMID- 9576186
TI  - A CD4+ proliferation of large granular lymphocytes expresses the protease
      activated receptor-1.
AB  - The platelet-type thrombin receptor was the first member to be identified in a
      family of protease activated receptors (PARs) and has been designated PAR-1. We
      recently reported that the large granular lymphocytes (LGLs) in patients with
      proliferations of CD8+ cells co-expressed PAR-1 and the expression of PAR-1
      correlated with the expression of CD57. Here we show, by three-colour
      immunofluorescence, that the LGLs from a patient with a rare CD4+ CD57+
      monoclonal expansion also expressed PAR-1. Northern blot analysis confirmed the
      presence of high levels of mRNA for PAR-1 in these LGLs.

PMID- 9576187
TI  - Differentiation-linked changes in granulocyte-macrophage colony-stimulating
      factor receptor mediated signalling in the HL-60 promyelocytic cell line.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the
      proliferation and maturation of immature myeloid progenitor cells and primes
      mature cell function in phagocytes. To investigate whether the biochemical events
      following the binding of GM-CSF to its receptor are differentiation dependent we
      analysed GM-CSF mediated activation of the JAK 2-STAT 5 and MAP kinase pathways
      in undifferentiated HL-60 cells and HL-60 cells induced to differentiate with
      dimethyl sulphoxide (DMSO) or retinoic acid (RA). GM-CSF stimulated MAP kinase
      activation in both the undifferentiated and differentiated HL-60 cells.
      Activation of MAP kinase (expressed as a proportion of total cellular MAP kinase)
      was maximal at 5 min and of similar magnitude in both cell types. There was,
      however, a marked difference in the later kinetics of activation, with the
      response being transient in the undifferentiated cells and disappearing within 15
      min, whereas it was prolonged and persisted for at least 60 min in the
      differentiated cells. GM-CSF mediated activation of STAT 5 was markedly increased
      (15-20-fold) after differentiation of HL-60 cells but the kinetics of activation
      did not change. The increase in STAT 5 activation was not due to a change in
      total cellular STAT 5 expression but correlated with increased JAK-2 protein
      levels. These data show that in the HL-60 cell model, differentiation modulates
      the activation of signalling molecules downstream of the GM-CSF receptor.

PMID- 9576189
TI  - Comparison of bone marrow transplant and chemotherapy for relapsed childhood
      acute lymphoblastic leukaemia: the MRC UKALL X experience. Medical Research
      Council Working Party on Childhood Leukaemia.
AB  - We examined the outcome of the 489 children with acute lymphoblastic leukaemia
      (ALL) who relapsed in the UKALL X trial, and produced graphical displays of
      adjusted comparisons of event-free survival (EFS) for chemotherapy versus bone
      marrow transplantation (BMT) from a sibling or volunteer unrelated donor, and
      autologous BMT (ABMT). EFS at 5 years was only 3% (95% CI 0-6%) for children who
      relapsed in the bone marrow (BM) within 2 years of diagnosis, irrespective of
      type of post-relapse treatment, whereas for those with late extramedullary
      relapse it was 66% (95% CI 48-85%). Comparison of the types of treatment did not
      show benefit for ABMT. For allogeneic BMT the overall reduction in the odds of an
      event was 26% (95% CI 1-51%) (2P= 0.05), resulting in an absolute increase in 5
      year event-free survival of 14% (from 26.4% to 40.7%). New approaches are needed
      for children with early BM relapses whose prognosis is virtually hopeless with
      current therapy; however, a conventional chemotherapy approach may be justifiable
      for late extramedullary relapses. For the remaining patients (71%), with later BM
      or early extramedullary relapses, the optimal treatment is still not clear. This
      uncertainty warrants a formal randomized comparison of BMT and chemotherapy, to
      avoid the biases due to unmeasurable selection factors.

PMID- 9576188
TI  - Deficiency of glycosylphosphatidyl inositol-anchored proteins in patients with
      aplastic anaemia does not affect response to immunosuppressive therapy.
AB  - Deficient expression of glycosylphosphatidyl inositol (GPI)-anchored proteins in
      aplastic anaemia (AA) patients has previously been reported to be associated with
      a poor response to immunosuppressive (IS) therapy. Here we report the response to
      IS therapy of 111 patients with AA and correlate this with GPI-anchored protein
      expression on peripheral blood cells by flow cytometry. A GPI-anchored protein
      deficient population was identified in 15% (17/111) of patients with AA who had a
      negative Ham's test and no laboratory evidence of haemolysis. Patients were
      treated with antilymphocyte globulin and/or cyclosporin A, or oxymetholone. Bone
      marrow transplantation was performed in 12 patients, seven of whom had not
      responded to IS therapy. In patients tested for CPI-anchored protein expression
      prior to IS therapy there was no difference in response rate to IS therapy
      between AA patients with a GPI-anchored protein deficiency and those with normal
      GPI-anchored protein expression (50% response rate versus 75%, respectively).
      Survival in these two groups was similar at 90% with follow-up over 140 months
      from diagnosis. Eight of the 17 AA patients who developed a GPI-anchored protein
      deficient population later went on to develop a positive Ham's test. From this
      study we demonstrate a lower incidence of GPI-anchored protein deficiency in AA
      patients compared with previous reports. In addition we have shown that the
      presence of a GPI-anchored protein-deficient cell population in patients with AA
      who have a negative Ham's test is not a poor prognostic factor in terms of
      response and survival after IS therapy.

PMID- 9576190
TI  - Progenitor cell subsets and engraftment kinetics in children undergoing
      autologous peripheral blood stem cell transplantation.
AB  - The main objective of the present study was to determine the role of CD34+ cell
      subsets in the haemopoietic recovery of children undergoing peripheral blood stem
      cell transplantation. For this purpose, 38 leukaphereses from 33 children with
      malignancies mobilized with G-CSF were analysed. Using dual-colour flow
      cytometry, different subpopulations of CD34+ cells were quantified and the number
      of each reinfused subsets correlated with haemopoietic resurgence. Multivariate
      analysis showed that the number of CD34+CD38- cells and CD34+CD38+ cells
      correlated better with time to neutrophil and platelet recovery, respectively,
      than the total number of CD34+ cells. Threshold values for rapid haemopoietic
      recovery, determined by the receiver operating characteristic analysis, were
      found to be 0.5 X 10(6) CD34+CD38- cells for neutrophil engraftment, and
      2.0x10(6) CD34+CD38+ cells for platelet recovery. It is suggested that the
      analysis of CD34+ cell subsets could increase understanding of the repopulation
      capacity of a given leukapheresis product in peripheral blood stem cell
      transplantation procedures in children. In particular, this procedure could be
      extremely useful when low numbers of CD34+ cells are collected.

PMID- 9576192
TI  - Selective expansion of normal haemopoietic progenitors from chronic myelogenous
      leukaemia marrow.
AB  - CD34+ and CD34+ DR- cells from the bone marrow (BM) of chronic-phase chronic
      myelogenous leukaemia (CML) patients at diagnosis were tested for their colony
      forming ability in response to early and intermediate-late colony stimulating
      factors (CSFs). Molecular analysis revealed that 55.6+/-9% SD of CD 34+ DR-
      colonies, in which actin and ABL mRNA were detectable, expressed the product of
      the BCR-ABL gene. The percentage and the clonogenic efficiency of CML DR- cells
      were significantly lower than those of comparable DR- cells from normal donors.
      However, clonogenic assays using recombinant human CSFs demonstrated a remarkable
      proliferation of CML cells when stimulated by SCF, IL-11 and IL-3, used as single
      factors in the presence of erythropoietin (EPO) and was almost entirely due to
      erythroid progenitors. Conversely, optimal stimulation of CD34 +DR- cells from
      normal donors required co-incubation with three or more CSFs. Stroma-noncontact
      long-term cultures were then established in the presence of exogenous CSFs and
      human irradiated allogeneic stromal layers or the murine stromal cell line M2
      10B4, engineered to produce G-CSF and IL-3. In these cultures the combination of
      SCF and IL-3 induced a 25.4 +/- 5 SD, 40 +/- 6 SD and 20.5 +/- 6 SD fold increase
      of colony-forming unit cells (CFU-C), at weeks 2, 4 and 5, respectively. At the
      same time-points the number of primitive long-term culture initiating cells (LTC
      IC) showed a 4 +/- 2 SD, 3.3 +/- 1.5 SD and 2.3 +/-1 SD fold increase compared to
      baseline values. BCR-ABL mRNA analysis of single colonies demonstrated that 27 +/
      9% SD and 7 +/- 3% SD CFU-C at weeks 4 and 5, respectively, expressed the fusion
      gene, whereas leukaemic LTC-IC disappeared from the culture by week 2. These
      results suggest that leukaemic CD34+ DR- cells have a different pattern of
      response to CSFs than normal cells. In addition, we established culture
      conditions which allow selective expansion of benign haemopoietic cells
      coexisting with leukaemic progenitors.

PMID- 9576191
TI  - Mobilization of Philadelphia-negative peripheral blood progenitor cells with
      chemotherapy and rhuG-CSF in chronic myelogenous leukaemia patients with a poor
      response to interferon-alpha.
AB  - The purpose of this cooperative study was to evaluate the quantity and quality of
      Ph1-negative progenitor cells mobilized in the peripheral blood of patients with
      chronic myelogenous leukaemia soon after aplasia induced by chemotherapy. 32
      patients ineligible for allografting who were cytogenetically refractory to
      interferon-alpha (IFN-alpha) were entered into this study. The chronic phase
      varied widely, with a median duration of 17 months (range 3-90 months). All
      patients were treated with intensive conventional chemotherapy regimens and
      recombinant human granulocyte colony-stimulating factor (rhuG-CSF, lenograstim).
      Peripheral blood progenitor cells (PBPC) were harvested by leukaphereses during
      early recovery from chemotherapy-induced aplasia. A total of 119 leukaphereses
      were performed. Median numbers of CD34+ cells and CFU-GM collected were 2.04 x
      10(6)/kg and 2 9 x 10(4)/kg, respectively. There was a significant correlation
      between white cell count and number of CD34+ cells in the leukaphereses (P =
      0.0001, r2 = 0.41, n = 104). A strict correlation between the number of CD34+
      cells and CFU-GM in the leukapheretic product (P = 0.0001, r2 = 0.39, n = 110)
      was observed. 21% of evaluable patients (6/29) achieved a complete cytogenetic
      remission in the leukapheretic product and the other four patients achieved a
      major cytogenetic response for an overall response of 35% (10/22 patients). To
      date, 16 patients have been autografted and are alive. Five of them are Ph1
      negative (three patients) or partially Ph1-negative (two patients). In
      conclusion, despite the high-risk characteristics of this study population, Ph1
      negative PBPC were successfully mobilized in more than one-quarter of patients
      using a chemotherapy plus rhuG-CSF regimen. The importance of this achievement is
      increased by the current lack of other practical methods of rescuing Ph-negative
      cells in such patients.

PMID- 9576193
TI  - Marked improvements in outcome with chemotherapy alone in paediatric acute
      myeloid leukemia: results of the United Kingdom Medical Research Council's 10th
      AML trial. MRC Childhood Leukaemia Working Party.
AB  - 359 eligible children with acute myeloid leukaemia (AML) entered the MRC AML 10
      trial between May 1988 and March 1995. Patients received four courses of
      intensive induction and consolidation chemotherapy, with or without subsequent
      autologous (A-BMT) or allogeneic (allo-BMT) bone marrow transplant. There were
      randomized comparisons of thioguanine versus etoposide in induction and of A-BMT
      versus not. Allo-BMT was recommended for patients with a HLA-matched sibling and
      was evaluated by donor versus no donor comparison. The complete remission rate
      was 92%. In first remission there were 20 deaths during consolidation
      chemotherapy and 11 after BMT (8/61 allo-BMTs. 1/60 A-BMTs and 2/4 matched
      unrelated donor transplants). The relapse rate was low, decreasing from 26% in
      the first year to 2% in the fourth. Long-term outcome was excellent with survival
      at 7 years from entry of 56% and event-free survival of 48%. There were no
      significant differences between thioguanine and etoposide, whereas both A-BMT and
      allo-BMT reduced relapse risk but did not produce a significant survival benefit.
      It appears that over half the children entered into AML 10 are cured, a result
      which compares favourably with other reported series. We conclude that four
      courses of intensive chemotherapy are an effective approach to the treatment of
      paediatric AML, which avoids the acute toxicity and long-term side-effects of BMT
      and also avoids the need for prolonged maintenance therapy or cranial
      irradiation.

PMID- 9576194
TI  - Mutations of the granulocyte-colony stimulating factor receptor in patients with
      severe congenital neutropenia are not required for transformation to acute
      myeloid leukaemia and may be a bystander phenomenon.
AB  - Point mutations of the granulocyte-colony stimulating factor receptor (G-CSFR)
      resulting in an abnormally truncated receptor have been implicated in the
      pathogenesis of some cases of severe congenital neutropenia (SCN) and in the
      transformation of SCN to acute myeloid leukaemia (AML). We report here studies in
      11 patients with SCN. No mutations were detected in the one patient who developed
      AML indicating that development of such mutations is not a prerequisite for
      transformation. Truncation mutations were detected in a minor percentage of
      transcripts from two other patients. In one patient the mutation has been
      constant at a low level (5-10% of total mRNA and 2/40 myeloid colonies) for 2
      years. In the other patient the mutation was acquired, remained present at low
      levels for nearly 3 years and then spontaneously disappeared. Both patients had
      polyclonal haemopoiesis. We hypothesize that these mutations do not cause SCN,
      are randomly acquired with the mutant clone being expanded to detectable levels
      by high levels of exogenous or endogenous G-CSF, and may disappear by clonal
      succession. In a pre-leukaemic marrow the mutated subclone could achieve high
      levels, but this does not necessarily indicate a primary role of the mutant
      receptor in the leukaemogenic process.

PMID- 9576195
TI  - Cytotoxic effectors activated by low-dose IL-2 plus IL-12 lyse IL-2-resistant
      autologous acute myeloid leukaemia blasts.
AB  - We have investigated the susceptibility of primary acute myeloid leukaemia (AML)
      samples to the lytic action of normal peripheral blood mononuclear cells (PBMC),
      as well as of the patients' autologous and allogeneic PBMC collected at the time
      of remission following stimulation with different concentrations of interleukin
      (IL)-2 and IL-12, both alone and in variable combinations. Primary AML blasts
      were resistant to IL-2-activated PBMC effectors generated from normal
      individuals, allogeneic and autologous patients in five, six and eight of the 10
      AML samples tested, respectively, IL-12 alone proved ineffective in generating
      anti-leukaemic activity, whereas, in combination, the two cytokines induced anti
      leukaemic killing in all five cases resistant to normal PBMC, in 4/6 samples
      resistant to allogeneic AML effectors and in 5/8 cases resistant to autologous
      effectors. In each case the lytic effect was maintained at the lowest cytokine
      combination (10 + 10 IU/ml) utilized. The suggestion of a synergistic effect was
      further strengthened by the evidence that at the lowest doses of IL-2 and IL-12
      the degree of killing was greater than that promoted by each cytokine
      independently. The results of this study suggest that two major limitations
      associated with the administration of IL-2 to AML patients, the resistance of the
      blasts to IL-2-generated killing and the toxicity associated with high-dose IL-2,
      may be overcome by the combined use of very low doses of IL-2 and IL-12. As IL-2
      resistant blasts may be lysed by a low-dose combination of IL-2/IL-12,
      feasibility studies with this cytokine combination are worthy of exploration in
      vivo.

PMID- 9576196
TI  - Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia
      by quantitative flow cytometry.
AB  - The clinical significance of detecting minimal residual disease (MRD) in B
      lineage acute lymphoblastic leukaemia (ALL) was evaluated by quantitative flow
      cytometry using a combination of TdT with CD10 and CD19. 53 patients with B-cell
      precursor ALL were followed during and after completion of treatment (median
      follow-up 23 months). Nine patients relapsed and MRD had been detected in six of
      them, 5-15 weeks before relapse despite morphological complete remission. 43
      patients remain in clinical remission and in none of these was MRD detected.
      Disease-free survival based on the detection of MRD by flow cytometry showed a
      statistically significant difference between both groups (P<0.0001). The absence
      of MRD correlates with a low relapse rate, whereas the presence of MRD predicted
      early relapse. This study has shown that flow cytometry can improve the
      morphologic assessment of bone marrow (BM) remission status in B-lineage ALL. The
      finding of < 5% blasts in BM aspirates did not correlate with 'true' remission in
      a proportion of cases as residual leukaemic blasts were detected by flow
      cytometry in nine samples from six patients. On the other hand, the presence of >
      5% blasts assessed by morphology was not necessarily a feature of relapse in five
      patients as these cells were shown to have a phenotype identical to normal TdT
      negative B-cell precursors. Quantitative flow cytometry was more informative than
      conventional morphology to assess remission status and showed a strong
      correlation with clinical outcome. This methodology is useful to define MRD in
      the majority of patients with B-lineage ALL and should be tested in prospective
      clinical trials.

PMID- 9576198
TI  - VH gene expression in hairy cell leukaemia.
AB  - Hairy cells are characterized by their typical morphology and expression of
      specific surface antigens. Although their B-cell origin is now confirmed, their
      exact position in B-cell development remains unclear. To better define the origin
      of hairy cells, we analysed the immunophenotype and the Ig VH nucleotide sequence
      of seven cases of hairy cell leukaemia (HCL). Six of them were typical HCL and
      the remaining case corresponded to a variant HCL. Analysis of sequenced VH genes
      revealed that the VH1 family was used in one case, VH2 in one, VH3 in two, VH4 in
      two and VH5 in one. No preferential usage of VH genes was observed in this small
      series. In five cases high rates of somatic mutations were observed, with a
      predominance of mutations and replacements in CDR regions for three. indicating
      that these cells originate from cells that have been exposed to the hypermutation
      mechanism. The distribution of mutations in our small series provides some
      evidence of a selective mutational process.

PMID- 9576197
TI  - Trisomy 12 is seen within a specific subtype of B-cell chronic
      lymphoproliferative disease affecting the peripheral blood/bone marrow and co
      segregates with elevated expression of CD11a.
AB  - In order to delineate the specific morphological and immunophenotypic features of
      B-cell lymphoproliferative disorders associated with trisomy 12, 172 sequential
      unselected cases of CD19+CD5+ B-cell disorders, primarily affecting the
      peripheral blood and bone marrow, were studied. Trisomy 12 was found in 24 cases
      (13.9%), with all cases morphologically classified as either CLL-PL or CLL-mixed
      by FAB criteria. Trisomy 12 was not found in any cases of typical CLL. Trisomy 12
      cases demonstrated a significant higher expression of CD11a (P<0.0001) and CD20
      (P<0.0006) when compared to cases with the equivalent morphology and
      immunophenotype, but without the chromosomal abnormality. Trisomy 12 cases also
      demonstrated a higher frequency of FMC7, CD38 expression and moderate to strong
      surface immunoglobulin staining. However, no correlation was detected between the
      percentages of trisomy 12 cells and cells expressing CD11a, CD38, FMC7 or sIg
      mean fluorescent intensity. Cells from trisomy 12 positive cases were sorted
      according to their CD11a expression using fluorescent activated cell sorting.
      There was a significant increase in the percentage of trisomy 12 cells within the
      CD11a+ sorted fraction compared to the unsorted population (P < 0.05), implying
      that trisomy 12 is associated with increased expression of CD11a. With the highly
      specific morphological and immunophenotypic features demonstrated by trisomy 12
      cases in this study, it is highly likely that these cases constitute a specific
      group of B-cell lymphoproliferative disorders.

PMID- 9576199
TI  - Evaluation of immunotoxins containing single-chain ribosome-inactivating proteins
      and an anti-CD22 monoclonal antibody (OM124): in vitro and in vivo studies.
AB  - Immunotoxins were prepared with three ribosome-inactivating proteins (RIP),
      momordin, pokeweed antiviral protein from seeds (PAP-S) and saporin-S6, linked to
      the anti-CD22 monoclonal antibody OM124. These immunotoxins inhibited protein
      synthesis by CD22-expressing cell lines Daudi, EHM, BJAB, Raji and BM21 with IC50
      (concentration causing 50% inhibition) ranging from < 5 x 10(-15) to 7.6 x 10(
      11) M as RIP, and IC90 (concentration causing 90% inhibition) ranging from 5 x
      10(-14) to 5 x 10(-8)M, with no effect on a CD22-negative HL60 cell line at the
      highest concentration tested (5 x 10[-8] M). Apoptosis was induced in sensitive
      cells. The formation of bone marrow colonies was inhibited by no more than 40% by
      the immunotoxins at concentrations up to 10(-9) M. Treatment with the
      immunotoxins, alone or in combination, significantly extended the survival time
      of mice bearing transplanted Daudi cells. A treatment with cyclophosphamide and
      OM124/saporin immunotoxin was particularly effective in SCID mice transplanted
      with a low number of cells (3 x 10[-6]), when 60% of the animals remained tumour
      free.

PMID- 9576200
TI  - Prognostic value of cytogenetics in multiple myeloma.
AB  - Karyotypic studies of bone marrow were conducted in 79 previously untreated
      patients with multiple myeloma who received a standard programme of chemotherapy.
      An abnormal karyotype was observed in 46% of patients, virtually all showing
      multiple abnormalities consistent with a long period of preclinical clonal
      evolution. Patients with an abnormal pattern showed various aberrations with
      hyperdiploidy in 64%, pseudodiploidy in 5% and hypodiploidy in 31%. The number of
      chromosomes affected ranged from two to 19 (median 10), with at least one trisomy
      in 83%, one monosomy in 75%, and one translocation in 42% of patients. Lymphoma
      like karyotypes were present in 17% of patients with an abnormality but were not
      associated with atypical clinical features, such as an extramedullary mass,
      leukaemia, or increased serum lactate dehydrogenase. Monosomy or deletion of
      chromosome 13 was present in 47% of patients with an abnormal pattern, who lived
      for a shorter duration (median 10 months) than patients with other abnormalities
      (median 34 months) or with diploidy (median 35 months). The cause of the short
      survival of patients with monosomy or deletion of chromosome 13 was not clear,
      but further studies on the relationship with specific oncogenes are indicated.

PMID- 9576201
TI  - MRC trial of alpha2b-interferon maintenance therapy in first plateau phase of
      multiple myeloma. MRC Working Party on Leukaemia in Adults.
AB  - Plateau phase has been achieved in 64% of all newly diagnosed patients with
      multiple myeloma treated with the ABCM (adriamycin, BiCNU, cyclophosphamide and
      melphalan) regimen in the Medical Research Council (MRC) trials; this stable
      clinical stage of the disease is associated with no more than minimal symptoms.
      Several studies have found that alpha-interferon (alpha-IFN) maintenance therapy
      increases the duration of plateau phase, but it is less clear if this translates
      into prolonged survival. We report the effect of alpha-IFN on the duration of
      plateau phase and overall survival in a trial with 284 patients who were
      randomized to receive alpha2b-IFN (Intron-A) or no maintenance therapy during
      first plateau phase. The minimum follow-up after randomization was 21 months.
      There was no significant difference in the overall survival between the two
      treatment groups (X2=0.32, P=0.57). There was a trend towards longer relapse-free
      survival in the patients allocated alpha-IFN, but this trend to longer plateau
      phase was not statistically significant (X2 = 1.62, P = 0.2). Disease progression
      at relapse on alpha-IFN appears to be more severe with greater elevations from
      plateau levels of serum paraprotein (P = 0.06) and beta2-microglobulin (P= 0.03)
      levels. Physicians tended to start chemotherapy sooner after diagnosis of relapse
      when patients had received alpha-IFN (P = 0.16). Although, in common with most
      other studies, there is a trend for patients treated with alpha-IFN to have a
      longer plateau phase, this is counteracted by morbidity attributable to the
      treatment and a somewhat shortened survival post relapse. Meta-analysis of
      interferon trials is required to assess whether the minor trend for longer
      survival in patients maintained on alpha-IFN found in some studies is significant
      and, if so, the extent of this advantage.

PMID- 9576202
TI  - Promising activity of gemcitabine in refractory high-grade non-Hodgkin's
      lymphoma.
AB  - Three patients (aged 68-75 years) with histologically confirmed relapsed or
      refractory high-grade non-Hodgkin's lymphoma were entered in this pilot study in
      which gemcitabine 800 mg/m2 was given as a 30 min i.v. infusion once a week for 3
      weeks. One patient responded with complete remission and the other two with
      partial remission and stable disease for 2 and 3 months, respectively.
      Haematological toxicity was modest with grade 4 leucopenia (one cycle) and grade
      4 thrombocytopenia (two cycles). The activity and mild toxicity seen with
      gemcitabine suggest that this agent should be further evaluated in the treatment
      of high-grade non-Hodgkin's lymphoma.

PMID- 9576203
TI  - A phase II trial of interleukin-2 in myelodysplastic syndromes.
AB  - Patients with myelodysplastic syndromes (MDS) show a decrease in the number and
      function of natural killer (NK) cells, including lymphokine activated killer
      (LAK) cell activity. Interleukin-2 (IL-2) stimulates the proliferation and
      activity of these lymphocytes. Anecdotal clinical experience has shown
      haematological and cytogenetic improvement in myelodysplasia by low-dose IL-2
      treatment. A total of 10 patients with MDS were treated with 1 million units of
      IL-2 subcutaneously daily for 12 weeks. Even though improvement in CD16+/CD56+
      cell numbers was seen in a majority of the patients, the haematological status
      and transfusion requirements remained unchanged. There was minimal toxicity from
      this therapy.

PMID- 9576204
TI  - A case of hypereosinophilic syndrome associated with factor V Leiden mutation and
      thrombosis.

PMID- 9576205
TI  - A case of pseudolymphoma leukaemia syndrome following cefixime.

PMID- 9576206
TI  - Venous infarction of a testicle following factor IX concentrate (DEFIX)

PMID- 9576207
TI  - A case of neonatal alloimmune thrombocytopenia complicated by preceding maternal
      idiopathic thrombocytopenic purpura.

PMID- 9576208
TI  - Midterm results after minimally invasive coronary surgery (LAST operation)
AB  - BACKGROUND: Our experience with a left internal thoracic artery graft to the left
      anterior descending artery via a left anterior small thoracotomy is reviewed to
      evaluate midterm results. METHODS: From November 1994 to April 1997, four hundred
      sixty patients were scheduled to undergo a left internal thoracic artery graft to
      the left anterior descending coronary artery via a left anterior small
      thoracotomy; 26 of these patients (5.7%) were converted and 434 of them had the
      operation. Two hundred fourteen patients (49.3%) had isolated disease of the left
      anterior descending artery, and 220 patients (50.7%) had multiple vessel disease.
      A sufficient length of the left internal thoracic artery was harvested to reach
      the left anterior descending artery. RESULTS: Three hundred nine patients (71.2%)
      underwent extubation by hour 2. Mean intensive care unit stay was 4.2 +/- 4.5
      hours; mean postoperative hospital stay was 66 +/- 29 hours; the 30-day mortality
      rate was 1.1%; the late mortality rate was 1.4%. Eighteen patients underwent
      reoperation early (< or = 30 days), and eight patients underwent reoperation late
      (> 30 days) because of conduit/anastomotic malfunction. Four patients underwent
      reoperation with patent anastomosis for progression of disease (n = 3) or
      pericarditis (n = 1). Three patients had a percutaneous transluminal coronary
      angioplasty. Cumulating angiographic and stress Doppler flow assessment results,
      a patent anastomosis was obtained in 417 patients and a nonrestrictive
      anastomosis in 404 patients. Twenty-nine months after surgery, survival was 97.1%
      +/- 0.7% (95% confidence interval 90.5% to 100%) and event-free survival 89.4% +/
      1.2% (95% confidence interval 78.2% to 100%). In the last 190 patients, with our
      increased experience and better instruments, we obtained a patent anastomosis in
      188 patients (98.9%) and a nonrestrictive anastomosis in 185 (97.4%).
      CONCLUSIONS: Left anterior small thoracotomy gives acceptable midterm results.
      Incidence of patent and nonrestrictive anastomoses was satisfactory, especially
      in the most recent part of our experience, when the learning curve ended.

PMID- 9576210
TI  - Short-course thrombolysis as the first line of therapy for cardiac valve
      thrombosis.
AB  - OBJECTIVE: To retrospectively evaluate the clinical and echocardiographic
      criteria of thrombolytic therapy for mechanical heart valve thrombosis. METHODS:
      Nineteen consecutive patients with 22 instances of prosthetic heart valve
      thrombosis (14 mitral, 2 aortic, 3 tricuspid, and 3 pulmonary) were treated with
      short-course thrombolytic therapy as first option of treatment in absence of
      contraindications. The thrombolytic therapy protocol consisted of streptokinase
      (1,500,000 IU in 90 minutes) (n = 18) in one (n = 7) or two (n = 11) cycles or
      recombinant tissue-type plasminogen activator (100 mg in 90 minutes) (n = 4).
      RESULTS: Overall success was seen in 82%, immediate complete success in 59%, and
      partial success in 23%. Six patients without total response to thrombolytic
      therapy underwent surgery, and pannus was observed in 83%. Six patients showed
      complications: allergy, stroke, transient ischemic attack, coronary embolism,
      minor bleeding, and one death. At diagnosis, 10 patients evidenced atrial
      thrombus by transesophageal echocardiography, 3 of whom experienced peripheral
      embolism during thrombolysis. Four episodes of rethrombosis were observed (16%).
      The survivorship was 84% with a mean follow-up of 42.6 months. CONCLUSIONS: A
      short-course of thrombolytic therapy may be considered first-line therapy for
      prosthetic heart valve thrombosis. The risk of peripheral embolism may be
      evaluated for the presence of atrial thrombus by transesophageal echocardiography
      at diagnosis.

PMID- 9576209
TI  - Less invasive techniques for mitral valve surgery.
AB  - OBJECTIVE: Minimally invasive surgical techniques aim at reducing the
      consequences of currently used large incisions, such as bleeding, pain, and risk
      of infection. Although this new approach developed rapidly in coronary surgery,
      it remains questionable in mitral valve surgery. This article reports the longest
      experience with minimally invasive mitral valve surgery, with particular
      attention to approach and techniques. METHODS: From February 1996, the date of
      the first case of minimally invasive mitral valve reconstruction, to April 1997,
      22 patients with a mean age of 54 +/- 2.7 years were subjected to mitral valve
      surgery performed with less invasive techniques. Exposure of the mitral valve was
      achieved through a minithoracotomy (n = 12) or a ministernotomy (n = 10). Video
      assistance was used in all cases. Peripheral arterial cannulation (n = 21) and
      venous drainage (n = 22) were used in most cases. RESULTS: In this series, valve
      surgery consisted in 19 repairs, two replacements, and one closure of a
      periprosthetic leak. In two cases it was necessary to convert to a larger
      incision. The average duration of cardiopulmonary bypass was 157 +/- 8.2 minutes,
      ventilatory assistance 16 +/- 4.6 hours, and intensive care unit stay 2.1 +/- 0.4
      days. Two patients required reoperation for bleeding and another for early
      recurrence of mitral valve regurgitation. There were no deaths and all patients
      were discharged with normal valve function. At most recent follow-up, all
      patients were in functional class I, with resumption of normal activity.
      CONCLUSION: Mitral valve surgery can be performed safely by means of less
      invasive techniques, but with increased technical difficulty. A low asymmetric
      median sternotomy seems preferable to an anterior thoracotomy.

PMID- 9576211
TI  - Systematic clinical and angiographic follow-up of patients undergoing minimally
      invasive coronary artery bypass.
AB  - OBJECTIVE: We herein analyze the results of the systematic clinical and
      angiographic control performed in a series of 77 consecutive patients undergoing
      minimally invasive coronary artery bypass. METHODS AND RESULTS: From January 1995
      to June 1997, 77 patients underwent minimally invasive coronary artery bypass at
      our institution. There was one inhospital death, one noncardiac late death, and
      five patients had to be reoperated for graft malfunction. A total of 76 patients
      underwent postoperative angiographic follow-up. In 66 cases (86.8%) the thoracic
      artery graft, the target vessel, and the anastomosis were patent and functioning
      normally. In one case the graft was occluded. In the remaining nine cases the
      thoracic artery graft was patent but with major anomalies of either the
      anastomosis, the target vessel, or the course of the thoracic artery. Patients
      operated using especially designed instruments had angiographic results clearly
      superior to those of patients operated using conventional instrumentation
      (perfect patency rate 100% vs 81.8%). At a mean follow-up of 18 months, 98.5% of
      the surviving patients are asymptomatic with negative myocardial scintigraphy.
      CONCLUSIONS: The perfect patency rate of minimally invasive revascularization
      performed without the use of dedicated instruments is unacceptably low. The use
      of specific devices is likely to result in a substantial improvement in the
      angiographic results.

PMID- 9576212
TI  - Coronary artery bypass surgery as treatment for ischemic heart failure: the
      predictive value of viability assessment with quantitative positron emission
      tomography for symptomatic and functional outcome.
AB  - OBJECTIVES: To determine the predictive value of quantitative evaluation of
      myocardial viability on changes in left ventricular function, exercise capacity,
      and quality of life after coronary artery bypass grafting in patients with
      ischemic heart failure (congestive heart failure, New York Heart Association
      class > or = III) with and without angina. METHODS: Thirty-five patients, 14 with
      congestive heart failure and angina (CHF-angina) and 21 with congestive heart
      failure without angina (CHF-no angina) were studied at baseline and 6 months
      after coronary bypass grafting. Left ventricular function was evaluated with
      transthoracic echocardiography and radionuclide ventriculography. Myocardial
      viability was assessed with [18F]-2-fluoro-2-deoxy-D-glucose using positron
      emission tomography. Peak aerobic capacity (peak oxygen consumption) and
      anaerobic threshold were assessed with treadmill exercise test and quality of
      life with a questionnaire. RESULTS: A total of 286 of 336 dysfunctional left
      ventricular segments were viable. There were two perioperative deaths (5.7%) and
      three late deaths. Left ventricular ejection fraction increased from 23% +/- 7%
      to 32% +/- 9% (p < 0.0001), and a linear correlation was found between the number
      of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001).
      Receiver operating characteristics curve identified eight viable segments as the
      best predictor for increase of ejection fraction more than 5 percentage points.
      Peak oxygen consumption increased from 15 +/- 4 to 22 +/- 5 ml/kg per minute (p <
      0.0001). Preoperatively, anaerobic threshold was identified in one patient from
      the CHF-angina group and in all from the CHF-no angina group and increased from
      13 +/- 4 to 19 +/- 4 ml/kg per minute (p < 0.0001). Quality of life scores
      improved significantly in both groups. No correlation was found between the
      amount of viable dysfunctional myocardium and changes in exercise capacity or
      quality of life. CONCLUSIONS: In patients with postischemic congestive heart
      failure the amount of viable myocardium dictates the degree of improvement in
      left ventricular function after revascularization.

PMID- 9576213
TI  - Partial left ventriculectomy with mitral valve preservation in the treatment of
      patients with dilated cardiomyopathy.
AB  - OBJECTIVE: This study reports initial results of partial left ventriculectomy
      performed with preservation of the mitral valve in the treatment of 27 patients
      with idiopathic dilated cardiomyopathy. METHODS: Patients were in New York Heart
      Association class III or IV. Partial ventriculectomy was performed as an isolated
      procedure in four patients and associated with mitral annuloplasty in 23
      patients. There were four hospital deaths (14.8%) and the remaining patients were
      followed for 11.2 +/- 6 months. RESULTS: Decrease of left ventricular diastolic
      diameter (81.8 +/- 8.7 to 68.5 +/- 7.6 mm, p < 0.001) and improvement of left
      ventricular wall shortening (12% +/- 3.1% to 18.1% +/- 3.9%, p < 0.001) were
      demonstrated by echocardiography after the operation. Left ventricular
      radioisotopic angiography showed reduction of diastolic volume (495 +/- 124 ml to
      352 +/- 108 ml, p < 0.001) and increase of ejection fraction (17.7% +/- 4.6% to
      23.7% +/- 8.8%, p < 0.001). Right-sided heart catheterization demonstrated
      improvement of stroke index (24.3 +/- 7.7 ml/m2 to 28.3 +/- 7.6 ml/m2, p < 0.01)
      and decrease of pulmonary wedge pressure (23.2 +/- 8.8 mm Hg to 17 +/- 7 mm Hg, p
      < 0.01). Similar results were documented at 6 and 12 months of follow-up.
      Functional class improved from 3.6 +/- 0.5 to 1.4 +/- 0.6 (p < 0.001). However,
      seven patients died at midterm follow-up because of heart failure progression or
      arrhythmia-related events, and survival rate was 59.2% +/- 9.4% from 6 to 24
      months of follow-up. CONCLUSIONS: Partial left ventriculectomy performed with
      preservation of the mitral valve improves left ventricular function and
      congestive heart failure in patients with dilated cardiomyopathy. Nevertheless,
      the high incidences of heart failure progression and arrhythmia-related deaths
      observed after this procedure preclude its wide clinical application.

PMID- 9576214
TI  - Further evidence of gaseous embolic material in patients with artificial heart
      valves.
AB  - OBJECTIVE: We undertook this study to evaluate the hypothesis that most
      microemboli signals in patients with artificial heart valves are gaseous,
      assuming that microemboli counts in cerebral arteries would progressively decline
      with increasing distance from the generating heart valve. METHODS: A total of 10
      outpatients with CarboMedics (Sulzer Carbomedics Inc., n = 5) and ATS prosthetic
      heart valves (n = 5) in the aortic (n = 8), mitral (n = 1), or both aortic and
      mitral positions (n = 1) were recruited. Monitoring was performed simultaneously
      over the middle and anterior cerebral arteries and the common carotid artery for
      30 minutes with the 2 MHZ transducers of a color duplex scanner (common carotid
      artery) and pulsed-wave Doppler ultrasonography (intracranial arteries). All data
      were harvested in an eight-channel digital audio tape recorder, and microembolic
      signal counts were evaluated online by two separate observers. RESULTS:
      Significantly higher microembolic signal counts were recorded in the common
      carotid artery (112 [75 to 175]) compared with the middle and anterior cerebral
      arteries (30 [18 to 36], p < 0.0001). Interobserver variability was satisfactory
      (k = 0.81). CONCLUSIONS: Our results strongly argue for gaseous underlying
      embolic material in patients with artificial heart valves because bubbles are
      bound to implode with time.

PMID- 9576215
TI  - Preliminary report on prediction of spinal cord ischemia in endovascular stent
      graft repair of thoracic aortic aneurysm by retrievable stent graft.
AB  - OBJECTIVE: To predict spinal cord ischemia after endovascular stent graft repair
      of descending thoracic aortic aneurysms, temporary interruption of the
      intercostal arteries (including the aneurysm) was performed by placement of a
      novel retrievable stent graft (Retriever) in the aorta under evoked spinal cord
      potential monitoring. METHODS: From February 1995 to October 1997, endovascular
      stent graft repair of descending thoracic aortic aneurysms was performed in 49
      patients after informed consent was obtained. In 16 patients with aneurysms
      located in the middle and distal segment of the descending aorta, the Retriever
      was placed temporarily before stent graft deployment. The Retriever consisted of
      two units of self-expanding zigzag stents connected in tandem with stainless
      steel struts. Each strut was collected in a bundle fixed to a pushing rod, and
      the stent framework was lined with an expanded polytetrafluoroethylene sheet. The
      Retriever was delivered beyond the aneurysm through a sheath and was retracted
      into the sheath 20 minutes later. A stent graft for permanent use was deployed in
      patients whose predeployment test results with the Retriever were favorable.
      Evoked spinal cord potential was monitored throughout placement of the Retriever
      and stent grafting until the next day. RESULTS: The Retriever was placed in 17
      aneurysms in 16 patients. There were no changes in amplitude or latency of evoked
      spinal cord potential records obtained before or during Retriever placement.
      After withdrawal of the Retriever, all aneurysms were excluded from circulation
      immediately after permanent stent grafting. There were no changes in evoked
      spinal cord potential, nor were neurologic deficits seen after stent graft
      deployment in any patient. CONCLUSIONS: These results suggest that predeployment
      testing with the Retriever under evoked spinal cord potential monitoring is
      promising as a predictor of spinal cord ischemia in candidates for stent graft
      repair of thoracic aortic aneurysms.

PMID- 9576216
TI  - Intracoronary adenovirus-mediated transfer of immunosuppressive cytokine genes
      prolongs allograft survival.

PMID- 9576217
TI  - A novel charcoal-induced model of obliterative bronchiolitis-like lesions:
      implications of chronic nonspecific airway inflammation in the development of
      posttransplantation obliterative bronchiolitis.
AB  - OBJECTIVES: In this study, we describe the development of a nonallogeneic animal
      model of obliterative bronchiolitis-like lesions. Furthermore, we examined
      whether chronic rejection alone can lead to the development of obliterative
      bronchiolitis or whether additional nonspecific airway inflammation is required.
      METHODS: Part I: Rats were intratracheally injected with 0.2 ml of activated
      charcoal or sorbitol solution (carrier for charcoal control). Animals were put to
      death beginning at 2 weeks up to 20 weeks. Part II: Animals were divided into
      three groups: group I, underimmunosuppressed Brown Norway to Lewis lung
      allografts; group II, charcoal-treated underimmunosuppressed allografts; and
      group III, charcoal-treated rats. Animals were put to death at 3 months after
      transplantation. RESULTS: Part I: In charcoal-laden bronchioles, subacute
      nonspecific airway inflammation was detected at 2 weeks. Slow, subclinical
      fibroproliferation ensued during the following weeks. Obliterative bronchiolitis
      like lesions were observed in 80% of charcoal-treated animals at 12 weeks. Part
      II: Allografts developed extensive vascular lesions consistent with acute and
      chronic vascular rejection. Obliterative bronchiolitis-like lesions were scarcely
      detected. Charcoal-treated allografts demonstrated evidence of diffuse and severe
      obliterative bronchiolitis-like lesions. CONCLUSIONS: Transtracheal injection of
      activated charcoal into native lungs results in slowly progressive airway injury
      and inflammation leading to obliterative airway lesions. Inadequate
      immunosuppression primarily results in chronic vascular rejection but not
      obliterative bronchiolitis. Underimmunosuppressed allografts subjected to
      nonspecific airway inflammation develop obliterative airway lesions that are more
      prominent than in native lungs. This suggests that a cofactor to chronic
      rejection is likely necessary for the development of lung transplant obliterative
      bronchiolitis.

PMID- 9576218
TI  - Massive hiatal hernias: the anatomic basis of repair.
AB  - OBJECTIVES: In the repair of giant hiatal hernias, controversy persists as to
      whether an antireflux repair is required and whether a Collis gastroplasty is
      necessary. This study was undertaken to determine the location of the
      gastroesophageal junction in giant hiatal hernias with an intrathoracic stomach,
      as well as the outcome after repair without a Collis gastroplasty. METHODS: Fifty
      two patients were evaluated for a giant hiatal hernia, of whom 47 underwent
      surgical correction. Preoperative evaluation included esophagoscopy (n = 45),
      gastrointestinal series (n = 40), esophageal manometry (n = 20), and 24-hour pH
      testing (n = 13). The dominant clinical features were acute chest or abdominal
      pain (72%), heartburn (53%), and gastrointestinal bleeding (49%). The
      gastroesophageal junction was located in the mediastinum in 77% of patients, in
      the abdomen in 17%, and was not determined in 6%. Twenty-eight patients (59%) had
      clinical or objective evidence of reflux. Reduction with an antireflux repair
      without a gastroplasty was done in 47 (Belsey, n = 28; Nissen, n = 19). An
      excellent or good result was achieved in 38 patients (90%) with a median follow
      up of 45 months. CONCLUSIONS: These results, obtained without a Collis
      gastroplasty, are equivalent to those obtained by an antireflux repair with an
      esophageal lengthening procedure. The frequent location of the gastroesophageal
      junction in the mediastinum suggests that these massive hernias often are the
      result of progressive enlargement of a sliding component. An antireflux repair is
      therefore necessary in the majority of patients.

PMID- 9576220
TI  - Neurophysiologic assessment of nerve impairment in posterolateral and muscle
      sparing thoracotomy.
AB  - OBJECTIVE: This study was aimed at analyzing the degree of intercostal nerve
      impairment in posterolateral and muscle-sparing thoracotomy and at correlating
      the nerve damage to the severity of long-lasting postthoracotomy pain. METHODS:
      Neurophysiologic recordings were performed 1 month after either posterolateral or
      muscle-sparing thoracotomy to assess the presence of the superficial abdominal
      reflexes (mediated in part by the intercostal nerves), the somatosensory-evoked
      responses after electrical stimulation of the surgical scar, and the electrical
      thresholds for tactile and pain sensations of the surgical incision. RESULTS: The
      patients who underwent a posterolateral thoracotomy showed a higher degree of
      intercostal nerve impairment than the muscle-sparing thoracotomy patients as
      revealed by the disappearance of the abdominal reflexes, a larger reduction in
      amplitude of the somatosensory-evoked potentials, and a larger increase of the
      sensory thresholds to electrical stimulation for both tactile perception and
      pain. In addition, these neurophysiologic parameters were highly correlated to
      the postthoracotomy pain experienced by the patients 1 month after surgery,
      indicating a causal role for nerve impairment in the long-lasting postoperative
      pain. CONCLUSIONS: This study shows for the first time the pathophysiologic
      differences between posterolateral and muscle-sparing thoracotomy and suggests
      that the minor long-lasting postthoracotomy pain in muscle-sparing thoracotomy
      patients is partly due to a minor nerve damage. In addition, because nerve
      impairment is responsible for the long-lasting neuropathic component of
      postoperative pain, it is necessary to match specific treatments to the
      neuropathic pain-generating mechanisms.

PMID- 9576219
TI  - Operative approach for multiple primary lung carcinomas.
AB  - Of 908 patients who underwent operation for primary lung cancer between January
      1985 and June 1996, we considered 57 (6.3%) to have a second primary lung cancer,
      which was synchronous in 28 cases (3.1%) and metachronous in 29 cases (3.2%).
      Five-year survival for patients with synchronous and metachronous disease from
      initial treatment of cancer was 70.3% and 66.0%, respectively. Survival after the
      development of a metachronous lesion was 32.9% at 5 years. Sixteen of the
      synchronous second tumors (57%) were detected on preoperative radiography or
      bronchoscopy and 11 (39%) at the time of operation. Survival of patients at stage
      I or II from treatment of a synchronous lesion (p = 0.002) and of a metachronous
      second lesion (p = 0.028) was significantly better compared with those at stage
      III or IV. Therefore it is important to carefully examine a synchronous lesion
      before and during the operation of a primary lung cancer and to perform close
      follow-up surveillance for early detection of a metachronous lesion. In treating
      multiple lung carcinomas consideration should always be given to performing
      precise staging, aggressive operative approach for early stage, and oncologically
      sound parenchymal sparing procedures.

PMID- 9576221
TI  - Techniques and results in the management of multiple ventricular septal defects.
AB  - OBJECTIVE: The management of patients with multiple ventricular septal defects
      remains controversial. Primary closure, interventional catheter techniques, and
      palliative surgery all may have a role, and specific management guidelines remain
      undefined. METHODS: We reviewed the records of all 33 patients with multiple
      ventricular septal defects undergoing repair between January 1988 and October
      1996. Pulmonary artery hypertension was present in 21 patients (group 1), and
      pulmonary stenosis was present in the remaining 12 (group 2). Closure was
      accomplished from a right atriotomy alone in most patients, although an apical
      left ventriculotomy was used for apical defects. Among group 1 patients, the mean
      age at repair was 5.9 +/- 0.9 months. Major associated anomalies included
      coarctation (n = 6), straddling tricuspid valve (n = 1), and critical aortic
      stenosis (n = 1). Reoperation was performed in two patients for residual
      ventricular septal defects. Among group 2 patients, the mean age at repair was
      6.6 +/- 3.2 years. Major associated anomalies included tetralogy of Fallot (n =
      2), pulmonary stenosis (n = 4), double-outlet right ventricle with hypoplastic
      left ventricle (n = 1), and isolated left ventricular hypoplasia (n = 1). Three
      required reoperation for residual ventricular septal defect. RESULTS: There were
      no early or late deaths, no episodes of heart block, and no significant residual
      ventricular septal defects among group 1 patients. All group 1 patients remain
      free of significant residual cardiovascular conditions at a mean of 23.4 +/- 5.1
      months. Among group 2 patients, there was one early death in a patient with
      double-outlet right ventricle and left ventricular hypoplasia. Complete heart
      block occurred in two patients and one required late mitral valve replacement.
      There were no late deaths, seven remain alive without significant residual
      defects at a mean of 36.2 +/- 8.0 months, and two required transplantation for
      left ventricular failure. CONCLUSIONS: Primary repair for infants with multiple
      ventricular septal defects is associated with good late outcomes. The right
      atrial approach is satisfactory for most muscular defects, although limited
      apical left ventriculotomy was used for apical defects. Pulmonary artery banding
      should be limited to patients with complex associated defects.

PMID- 9576222
TI  - A modified repair technique for tricuspid incompetence in Ebstein's anomaly.
AB  - OBJECTIVE: A modified technique for tricuspid valve repair in Ebstein's anomaly
      restructures the valve mechanism at the level of the true tricuspid anulus by
      using the most mobile leaflet for valve closure without plication of the
      atrialized chamber. Midterm results of this therapeutic approach for patients
      with Ebstein's anomaly and tricuspid valve incompetence are reported. METHODS:
      Between October 1988 and April 1997, the incompetent tricuspid valve was repaired
      with our technique in 19 patients (12 female, 7 male; 2 to 54 years, mean 21
      years). The indication for operation was congestive heart failure of various
      degrees in all patients. Tricuspid incompetence was grade II in two patients,
      grade III in 14, and grade IV in three. Associated congenital malformations were
      simultaneously repaired (interatrial communication in 18, ventricular septal
      defect in two, pulmonary stenosis in two, mitral valve prolapse in one). Follow
      up ranged between 10 and 103 months (median 28 months) and was complete for all
      patients. RESULTS: There were no operative deaths. One patient with active
      endocarditis and pulmonary abscess died 2 months after the operation of recurrent
      sepsis; there were no late deaths. During follow-up, New York Heart Association
      functional class improved from 2.8 before the operation to 1.9 without recurrent
      cyanosis, and tricuspid incompetence decreased from a mean grade of 3.1 to one of
      0.9, without any echocardiographic deterioration of the tricuspid valve function
      or right ventricular dilation. CONCLUSIONS: Our technique allows tricuspid valve
      repair in patients with Ebstein's anomaly, even in cases usually reserved for
      primary valve replacement, without late functional deterioration.

PMID- 9576223
TI  - Repair of congenital tracheal stenosis with a free tracheal autograft.
AB  - OBJECTIVES: Evaluate the results of a technique for repair of congenital tracheal
      stenosis by use of a free tracheal autograft. METHODS: Between January 1996 and
      July 1997, six infants with congenital tracheal stenosis resulting from complete
      tracheal rings underwent repair with a free tracheal autograft. Mean age at the
      time of repair was 4.9 months; mean weight was 5.4 kg. The approach was through a
      median sternotomy with cardiopulmonary bypass for respiratory support. The
      trachea was incised anteriorly through the area of stenosis, the midportion of
      the stenotic trachea was excised, and an end-to-end anastomosis was carried out
      posteriorly. The excised tracheal segment (1.3 to 2.2 cm long) was used as a free
      autograft to patch the lower trachea anteriorly. In four infants the autograft
      was augmented in the upper trachea with pericardium; in two patients with a
      shorter length of stenosis, the autograft completed the repair. Simultaneous
      pulmonary artery sling repair (4), ligation and division of patent ductus
      arteriosus (3), cricoid split (2), atrial and ventricular septal defect repair
      (1), and complete atrioventricular canal repair (1) were performed at the time of
      tracheal repair. RESULTS: The infants were extubated and discharged at a mean of
      13 and 23 days postoperatively, respectively. One infant had recurrent tracheal
      stenosis related to the pericardial patch and required a tracheal stent and
      tracheostomy 4 months postoperatively. Our mean follow-up is 11 months.
      Bronchoscopic findings currently show widely patent tracheal lumina in all
      infants. CONCLUSIONS: The technique of free tracheal autograft with and without
      pericardial augmentation was successful in opening the airway of six infants with
      congenital tracheal stenosis and is currently our procedure of choice for
      children with this diagnosis.

PMID- 9576225
TI  - Fibrin sealant, aprotinin, and immune response in children undergoing operations
      for congenital heart disease.
AB  - OBJECTIVE: Most commercially available fibrin sealants contain aprotinin in doses
      of 1500 kallikrein inactivator units per milliliter. They are used in many
      operative disciplines. An elevated risk of hypersensitivity reactions exists at
      reexposure to aprotinin. Our aim was to examine the immunogenic potency of
      aprotinin as a fibrin sealant content. METHODS: We investigated 49 children with
      operatively treated congenital heart disease. All patients received aprotinin
      only topically as contained in fibrin sealant. Serum samples were drawn
      preoperatively, 1 week, 2 weeks, 6 weeks, and approximately 1 year after
      operation. They were analyzed for aprotinin-specific immunoglobulin G antibodies
      with a standard enzyme-linked immunosorbent assay and a fluorescence enzyme
      immunoassay for aprotinin-specific immunoglobulin E antibodies. RESULTS: At 1
      week, 2 weeks, 6 weeks, and 1 year, we found prevalences of 8% (2 of 26), 8% (2
      of 24), 6% (3 of 49), and 0% for aprotinin-specific Immunoglobulin E, and for
      aprotinin-specific immunoglobulin G 8% (2 of 26), 17% (4 of 24), 39% (19 of 49),
      and 12% (5 of 41). The doses of aprotinin given did not differ significantly in
      antibody-negative and antibody-positive patients; no significant factors could
      predict the immune response. CONCLUSIONS: Our findings show the existence of a
      subgroup of patients who had aprotinin-specific antibodies develop after topical
      aprotinin application. Any use of aprotinin must be carefully documented. If
      aprotinin use is planned in patients who previously underwent a surgical
      procedure, preexposure to aprotinin in any form must be sought to avoid
      unexpected anaphylactic reactions. The necessity itself and alternatives for
      aprotinin as a stabilizing agent in fibrin sealants merit consideration.

PMID- 9576224
TI  - Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide
      withdrawal in postoperative congenital heart disease.
AB  - OBJECTIVE: Inhaled nitric oxide therapy causes selective and sustained pulmonary
      vasodilation in patients with pulmonary hypertension; however, attempts to
      discontinue inhaled nitric oxide therapy may be complicated by abrupt life
      threatening events. Dipyridamole, a cyclic guanosine monophosphate-specific
      phosphodiesterase inhibitor, blocks the hydrolysis of cyclic guanosine
      monophosphate in vascular smooth muscle cells. METHODS: We studied 23 consecutive
      children who were treated with inhaled nitric oxide because of clinically
      significant pulmonary hypertension after surgery for congenital heart disease.
      Inhaled nitric oxide therapy was withdrawn before and after dipyridamole
      treatment of children in whom sustained elevations of pulmonary artery pressure
      developed for over 30 minutes. RESULTS: In 7 of 23 children, inhaled nitric oxide
      withdrawal caused a 40% increase in pulmonary artery pressure, a 17% decrease in
      systemic venous oxygen saturation, and a 46% increase in the ratio of mean
      pulmonary artery pressure to aortic pressure. Compared with children who had no
      significant increase in pulmonary artery pressure, children who experienced the
      development of prolonged pulmonary hypertension after inhaled nitric oxide
      therapy withdrawal had higher mean pulmonary artery pressure immediately before
      inhaled nitric oxide withdrawal (22 +/- 1 mm Hg versus 27 +/- 2 mm Hg; p = 0.04)
      and received inhaled nitric oxide for a longer duration (2 +/- 1 days versus 4 +/
      1 days; p = 0.01). Dipyridamole therapy attenuated the rise in pulmonary artery
      pressure and fall in systemic venous oxygen saturation in all six patients
      studied with rebound pulmonary hypertension after withdrawal of inhaled nitric
      oxide. CONCLUSION: We conclude that dipyridamole therapy acutely attenuates the
      adverse hemodynamic effects of rapid withdrawal of inhaled nitric oxide therapy.
      Children with higher pulmonary artery pressure and who are treated with inhaled
      nitric oxide for a longer duration may be at increased risk for adverse
      hemodynamic effects of inhaled nitric oxide therapy withdrawal. We speculate that
      dipyridamole therapy may sustain elevations of smooth muscle cyclic guanosine
      monophosphate induced by inhaled nitric oxide and that phosphodiesterase activity
      contributes to acute pulmonary hypertension after inhaled nitric oxide
      withdrawal.

PMID- 9576226
TI  - Esmolol for the management of pediatric hypertension after cardiac operations.
AB  - OBJECTIVE: Hypertension frequently occurs during the immediate postoperative
      period in children after repair of aortic coarctation but may also occur after
      repair of other congenital heart defects. Nitroprusside has often been used to
      control blood pressure in this setting. Because hypertension after coarctation
      repair is frequently associated with elevations in catecholamines, esmolol, a
      short-acting beta-blocking agent, may be an effective alternative. Therefore we
      undertook the first systematic investigation to determine the efficacy and
      disposition of esmolol in pediatric patients with acute hypertension after
      cardiac operations. METHODS: Twenty patients aged 1 month to 12 years (median
      25.6 months) with acute hypertension after cardiac operations received esmolol in
      an opened-labeled trial. Esmolol was titrated to a blood pressure less than or
      equal to the 90th percentile for age. RESULTS: Ten patients had coarctation
      repair and the remaining patients underwent repair of other congenital heart
      defects. On final esmolol dose (mean +/- standard deviation dosage 700 +/- 232
      microg/kg/min) there was a significant percent decrease in heart rate and
      systolic and diastolic blood pressures from postoperative values. Esmolol dose
      was significantly associated with percent reduction in systolic blood pressure.
      Final esmolol dose and total body clearance were significantly higher in patients
      after coarctation repair. There were significant associations between esmolol
      dose and esmolol blood concentrations at steady state. CONCLUSIONS: The dosage
      required to control hypertension in patients after repair of aortic coarctation
      was higher than patients who underwent repair of other congenital heart defects.
      Esmolol was effective in controlling blood pressure in 19 of 20 patients without
      adverse effects.

PMID- 9576227
TI  - Experimental right ventricle to pulmonary artery discontinuity: outcome of
      polyurethane valved conduits.
AB  - OBJECTIVE: The ideal substitute for the treatment of ventricle-pulmonary artery
      discontinuity remains a topic of controversy, because of calcifications and
      degeneration of biologic substitutes leading to subsequent reoperations. Because
      polyurethane valves used in ventricular assist devices show a satisfactory
      biocompatibility, the aim of this study was to evaluate a valved conduit composed
      of a Dacron graft incorporating a trileaflet 25 mm polyurethane valve. METHODS:
      The conduit was implanted between the right ventricle and the main pulmonary
      artery in adult sheep, with ligation of the proximal pulmonary artery. The
      animals received no medications. Serial hemodynamic data were collected at the
      time of implantation and at postoperative intervals of 6 and 12 months. RESULTS:
      The peak pressure gradient across the valve increased significantly between
      implantation (0.17 +/- 5.6 mm Hg) and 6 months after operation (7.3 +/- 3 mm Hg,
      p = 0.0007) and remained stable thereafter (6.7 +/- 3 mm Hg at 12 months),
      whereas the cardiac output remained unchanged (4.6 +/- 0.6 L/min at implantation,
      4 +/- 0.6 L/min at 6 months, and 3.9 +/- 1.1 L/min at 12 months). At the
      completion of the study, valve samples were processed and vapor coated with
      carbon for microscopic examination. There was one instance of nonadherent
      thrombus formation inside a cusp but no structural failures. The other valves
      were free of calcium deposits and no significant amounts of phosphorus could be
      detected by scanning electron microscopy and energy dispersive spectrometry.
      CONCLUSIONS: These data demonstrate the good hemodynamic performance, low
      thrombogenicity, and acceptable durability of the polyurethane valves implanted
      in the right side of the heart in a chronic sheep model.

PMID- 9576228
TI  - One hundred patients with the HeartMate left ventricular assist device: evolving
      concepts and technology.
AB  - BACKGROUND: Implantable left ventricular assist devices are common as a bridge to
      transplantation but are just reaching their goal as an alternative to
      transplantation. METHODS: From December 1991 until December 1996, 97 left
      ventricular assist devices were implanted as a bridge to transplantation, one as
      an alternative to transplantation, and two as a bridge to recovery. Included were
      64 pneumatic devices and 36 electric devices. Most patients (69%) had ischemic
      cardiomyopathy and most (53%) had had previous cardiac surgery. Preoperative
      circulatory support (extracorporeal membrane oxygenation) was used in 25.
      RESULTS: Perioperative insertion of a right ventricular assist device was unusual
      (11%). The mean duration of support with a left ventricular assist device (bridge
      to transplantation) was 70 +/- 41 days (up to 206 days). Survival to
      transplantation was 76%. Cause of death included multiple organ failure (n = 13),
      perioperative stroke (n = 5), device failure (n = 5), and controller disconnect
      (n = 1). Significant risk factors for death included (1) preoperative need for
      ventilator or extracorporeal membrane oxygenation, (2) elevated blood urea
      nitrogen, creatinine, or bilirubin, and (3) low pulmonary artery pressures. Risks
      after insertion of the left ventricular assist device were reoperation for
      bleeding, support with a right ventricular assist device, dialysis, or device
      failure. Catastrophic failure of the device occurred 14 times in 12 patients and
      was treated by emergency pump exchange in six instances. Only two device-related
      thromboembolic episodes were detected. Positive blood cultures were found in 59%
      of patients, driveline infection in 28%, and pump infection in 11%. CONCLUSIONS:
      The HeartMate device provided excellent hemodynamic support with low device
      related thromboembolic events. Infection and reliability of the device
      contributed to the high cost of therapy. These areas need to be improved for the
      left ventricular assist device to attain its goal as a viable alternative to
      transplantation.

PMID- 9576229
TI  - Does simultaneous antegrade/retrograde cardioplegia improve myocardial perfusion
      in the areas at risk? A magnetic resonance perfusion imaging study in isolated
      pig hearts.
AB  - OBJECTIVE: This study was designed to determine whether simultaneous
      antegrade/retrograde cardioplegia improves myocardial perfusion in areas supplied
      by occluded vessels. METHODS: Isolated pig hearts placed in a Langendorff
      preparation were divided into two groups. The left anterior descending coronary
      artery was occluded at its origin. In group 1 (n = 7), simultaneous
      antegrade/retrograde cardioplegia was conducted with use of a single perfusion
      unit with tubing in a Y-shaped configuration at the end, joined to the aorta and
      the coronary sinus. In group 2 (n = 8) simultaneous antegrade/retrograde
      cardioplegia was performed with two separate units, one for antegrade delivery of
      cardioplegic solution and the other for retrograde cardioplegic solution
      delivery. Myocardial perfusion in the region supplied by the left anterior
      descending artery and the region not supplied by this artery was assessed by
      magnetic resonance imaging, with use of a magnetic resonance contrast agent. The
      contrast agent was introduced into the common perfusion line in group 1 and into
      the aortic line only in group 2. RESULTS: Magnetic resonance images showed that
      the myocardium in the region supported by the left anterior descending artery
      could not be perfused with antegrade cardioplegic solution because of occlusion
      of the artery. During simultaneous antegrade/retrograde cardioplegia, however,
      the myocardium in the left anterior descending region was perfused by
      approximately 40% to 50% (group 1) or 20% to 30% (group 2) of the degree of
      perfusion in the region not perfused by the left anterior descending artery
      (100%). Almost no cardioplegic solution was delivered to the heart through the
      coronary sinus route during simultaneous antegrade/retrograde cardioplegia in
      both groups of hearts. Myocardial perfusion in the region supported by the left
      anterior descending artery was heterogeneous during simultaneous
      antegrade/retrograde cardioplegia. CONCLUSIONS: Simultaneous antegrade/retrograde
      cardioplegia significantly improved myocardial perfusion in jeopardized areas of
      the myocardium. The jeopardized myocardium was mainly perfused by the solution
      drained from the adjacent normal tissue. Elevated pressure at the coronary sinus
      during simultaneous antegrade/retrograde cardioplegia is responsible for the
      redistribution of antegradely delivered cardioplegic solution.

PMID- 9576230
TI  - The effect of nitric oxide synthase inhibitor on reperfusion injury of the brain
      under hypothermic circulatory arrest.
AB  - OBJECTIVE: The objective of this study was to investigate the protective effects
      of nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester
      hydrochloride, on reperfusion injury of the brain under hypothermic circulatory
      arrest. METHODS: After cardiopulmonary bypass was established using 12 piglets
      each weighing about 30 kg, the animals were cooled to a brain temperature of 20
      degrees C and circulatory arrest was performed for 90 minutes followed by
      reperfusion for 120 minutes. The level of nitric oxide within the brain was
      measured with a needle electrode inserted into the brain. In the treatment group,
      N(G)-nitro-L-arginine methyl ester hydrochloride was administered with an
      intravenous injection of 1.5 mg/kg at the onset of the reperfusion followed by a
      60-minute continuous venous infusion of 1.5 mg/kg/hr. RESULTS: In the control
      group, nitric oxide levels within the brain increased not during ischemia but
      during reperfusion, and the level after 120 minutes of reperfusion increased
      significantly compared with that of before circulatory arrest. But in the
      treatment group, N(G)-nitro-L-arginine methyl ester hydrochloride administered at
      the onset of reperfusion inhibited nitric oxide production during reperfusion. A
      significant difference was observed between the groups regarding the nitric oxide
      level after 120 minutes of reperfusion. Regarding cerebral blood flow, excess
      lactate, and cerebral tissue water content, no significant difference was
      observed between the groups. However, recovery of somatosensory evoked potential
      after 120 minutes of reperfusion was detected in all six animals in the treatment
      group, but none in the control group (p = 0.001). CONCLUSION: These data suggest
      that N(G)-nitro-L-arginine methyl ester hydrochloride protects the brain against
      reperfusion injury under hypothermic circulatory arrest.

PMID- 9576231
TI  - L-arginine, a nitric oxide precursor, attenuates ischemia-reperfusion injury by
      inhibiting inositol-1,4,5-triphosphate.
AB  - OBJECTIVE: We evaluated the effect of pretreatment with nitric oxide precursor
      before ischemia on recovery with reperfusion in rat hearts. METHODS: Isolated rat
      hearts were perfused with Krebs-Henseleit buffer without (C group) or with 3
      mmol/L L-arginine (A group) before 30 minutes of ischemia. The left ventricular
      function, including heart rate, developed pressure, maximal dp/dt, and coronary
      flow, were measured before pretreatment and after 10 and 30 minutes of
      reperfusion. Cyclic guanosine monophosphate (by radioimmunoassay), calcium (by
      absorption spectrophotometry), and inositol 1,4,5-triphosphate synthesized from
      tritiated myo-inositol (by ion-exchange chromatography preceding counting) were
      measured at the same times and immediately after ischemia. RESULTS: Recovery of
      ventricular function was significantly greater in the A group than in the C
      group. Pretreatment increased postischemic cyclic guanosine monophosphate content
      compared with the preischemic level (from 1.06 +/- 0.12 to 1.94 +/- 0.09 pmol/mg
      protein, p < 0.05). No change in cyclic guanosine monophosphate was evident in
      the C group. In the C group, inositol triphosphate content increased after 10
      minutes of reperfusion beyond the preischemic level (from 0.53 +/- 0.023 to 1.15
      +/- 0.045 cpm x 10(-3)/gm, p < 0.05) as did calcium at 30 minutes (from 4.12 +/-
      0.164 to 6.86 +/- 0.544 mmol/gm dry weight). In the A group, both of these
      increases were significantly attenuated. CONCLUSION: These data suggest that L
      arginine pretreatment may reduce calcium overload by increasing cyclic guanosine
      monophosphate production, which in turn downregulates inositol triphosphate
      synthesis during reperfusion.

PMID- 9576233
TI  - Abdominal aorta and visceral arteries visualized with transesophageal
      echocardiography during operations on the aorta.

PMID- 9576232
TI  - Microhemodynamics and leukocyte sequestration after pulmonary ischemia and
      reperfusion in rabbits.
AB  - OBJECTIVE: Investigation of leukocyte sequestration in alveolar capillaries and
      of microhemodynamic changes after pulmonary ischemia/reperfusion injury. METHODS:
      The kinetics of leukocyte passage and the hemodynamics in pulmonary
      microcirculation were investigated in 16 rabbits by intravital microscopy. Mean
      red blood cell velocity and the number of sticking leukocytes were measured in
      pulmonary arterioles, venules, and capillaries after 1 hour of tourniquet
      ischemia and 10 minutes and 1 hour after reperfusion. RESULTS: The decrease of
      red blood cell velocity after reperfusion was associated with a largely increased
      heterogeneity of blood flow. Immediately after the onset of blood flow,
      sequestered leukocytes were found in all microvascular segments. An increased
      number of leukocytes was present in arterioles, venules, and alveolar capillaries
      10 minutes and 1 hour after reperfusion. Concomitantly, width of alveolar septa
      was increased while arterial oxygen tension was reduced, indicating the
      development of interstitial pulmonary edema. CONCLUSION: Leukocytes are
      sequestered after pulmonary ischemia and reperfusion not only in alveolar
      capillaries but also in arterioles and venules, and they may contribute to the
      development of reperfusion edema.

PMID- 9576234
TI  - Delayed iatrogenic aortic dissection from coronary bypass managed with
      extraanatomic bypass.

PMID- 9576235
TI  - Biphasic release of secretory phospholipase A2 during and after cardiopulmonary
      bypass.

PMID- 9576236
TI  - Synchronous patent foramen ovale and bronchopleural fistula after right
      pneumonectomy: nonoperative management with survival.

PMID- 9576237
TI  - Influence of low-intensity anticoagulation and low-dose antiplatelet agent on
      coagulation-fibrinolysis system after mechanical prosthetic valve replacement.

PMID- 9576238
TI  - Assessment of long-term left internal thoracic artery graft patency by exercise
      Doppler echocardiography.

PMID- 9576239
TI  - Axillocoronary bypass for severely atherosclerotic aorta in coronary artery
      bypass grafting.

PMID- 9576240
TI  - Thoracoscopic approach for biopsy of the latissimus dorsi cardiomyoplasty wrap.

PMID- 9576241
TI  - Should the anticalcification effect of epoxy compound in vascular bioprostheses
      be judged after implantation in mongrel dogs?

PMID- 9576243
TI  - Minimally invasive coronary artery surgery.

PMID- 9576242
TI  - Early failure of freehand aortic stentless xenograft valves.

PMID- 9576244
TI  - Right heart bypass with an extracardiac conduit: a cautionary tale!

PMID- 9576245
TI  - Proton magnetic resonance spectroscopy for detection of axonal injury in the
      splenium of the corpus callosum of brain-injured patients.
AB  - OBJECT: This study was conducted to determine whether proton magnetic resonance
      spectroscopy (MRS) is a sensitive method for detecting diffuse axonal injury,
      which is a primary sequela of traumatic brain injury (TBI). Diffuse axonal injury
      is characterized by selective damage to white matter tracts that is caused in
      part by the severe inertial strain created by rotational acceleration and
      deceleration, which is often associated with motor vehicle accidents. This axonal
      injury is typically difficult to detect by using conventional imaging techniques
      because it is microscopic in nature. The splenium was selected because it is a
      site vulnerable to shearing forces that produce diffuse axonal injury. METHODS:
      The authors used proton MRS to evaluate the splenium, the posterior commissure of
      the corpus callosum, in normal control volunteers and in patients with TBI.
      Proton MRS provided an index of neuronal and axonal viability by measuring levels
      of N-acetyl aspartate (NAA). CONCLUSIONS: A majority of mildly brain injured
      patients, as well as those more severely injured, showed diminished NAA/creatine
      (Cr) levels in the splenium compared with normal control volunteers. The patients
      displaying lowered NAA/Cr in the splenium were also likely to exhibit lowered
      NAA/Cr in lobar white matter. Also, the levels of NAA/Cr in the splenium of
      normal volunteers were higher compared with those found in lobar white matter.
      Decreases in NAA/Cr levels in the splenium may be a marker for diffuse injury. A
      proton MRS examination may be particularly useful in evaluating mildly injured
      patients with unexplained neurological and cognitive deficits. It is concluded
      that MRS is a sensitive tool in detecting axonal injury.

PMID- 9576246
TI  - Cerebral perfusion pressure in head-injured patients: a noninvasive assessment
      using transcranial Doppler ultrasonography.
AB  - OBJECT: The authors studied the reliability of a new method for noninvasive
      assessment of cerebral perfusion pressure (CPP) in head-injured patients in which
      mean arterial blood pressure (ABP) and transcranial Doppler middle cerebral
      artery mean and diastolic flow velocities are measured. METHODS: Cerebral
      perfusion pressure was estimated (eCPP) over periods of continuous monitoring (20
      minutes-2 hours, 421 daily examinations) in 96 head-injured patients (Glasgow
      Coma Scale score < 13) who were admitted to the intensive care unit. All patients
      were sedated, paralyzed, and ventilated. The eCPP and the measured CPP (ABP minus
      intracranial pressure, measured using an intraparenchymal microsensor) were
      compared. The correlation between eCPP and measured CPP was r=0.73; p < 10(-6).
      In 71% of the examinations, the estimation error was less than 10 mm Hg and in
      84% of the examinations, the error was less than 15 mm Hg. The method had a high
      positive predictive power (94%) for detecting low CPP (< 60 mm Hg). The eCPP also
      accurately reflected changes in measured CPP over time (r > 0.8; p < 0.001) in
      situations such as plateau and B waves of intracranial pressure, arterial
      hypotension, and refractory intracranial hypertension. A good correlation was
      found between the average measured CPP and eCPP when day-by-day variability was
      assessed in a group of 41 patients (r=0.71). CONCLUSIONS: Noninvasive estimation
      of CPP by using transcranial Doppler ultrasonography may be of value in
      situations in which monitoring relative changes in CPP is required without
      invasive measurement of intracranial pressure.

PMID- 9576247
TI  - The persistent vegetative state after closed head injury: clinical and magnetic
      resonance imaging findings in 42 patients.
AB  - OBJECT: In this retrospective study, the authors analyzed the frequency,
      anatomical distribution, and appearance of traumatic brain lesions in 42 patients
      in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic
      resonance (MR) imaging was used to detect the number of lesions, which ranged
      from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases
      there was evidence on MR imaging of diffuse axonal injury, and injury to the
      corpus callosum was detected in all patients. The second most common area of
      diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem
      (74% of patients). In addition, 65% of these patients exhibited white matter
      injury in the corona radiata and the frontal and temporal lobes. Lesions to the
      basal ganglia or thalamus were seen in 52% and 40% of patients, respectively.
      Magnetic resonance imaging showed some evidence of cortical contusion in 48% of
      patients in this study; the frontal and temporal lobes were most frequently
      involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in
      this subgroup there was an 80% incidence of contralateral peduncular lesions in
      the midbrain. The most common pattern of injury (74% in this series) was the
      combination of focal lesions of the corpus callosum and the dorsolateral
      brainstem. In patients with no evidence of diffuse axonal injury in the upper
      brainstem (26% in this series), callosal lesions were most often associated with
      basal ganglia lesions. Lesions of the corona radiata and lobar white matter were
      equally distributed in patients with or without dorsolateral brainstem injury.
      Moreover, cortical contusions and thalamic, parahippocampal, and cerebral
      peduncular lesions were also similarly distributed in both groups. CONCLUSIONS:
      The data indicate that diffuse axonal injury may be the major form of primary
      brain damage in the posttraumatic persistent vegetative state. In addition, the
      authors demonstrated in this study that MR imaging, in conjunction with a precise
      clinical correlation, may provide useful supportive information for the accurate
      diagnosis of a persistent vegetative state after traumatic brain injury.

PMID- 9576248
TI  - Endoscopic treatment of carpal tunnel syndrome: a critical review.
AB  - OBJECT: The goal of this paper is to present a critical review of the endoscopic
      procedures currently in use for the treatment of carpal tunnel syndrome.
      Endoscopic techniques and outcomes are discussed. METHODS: An extensive review of
      published articles on the subject of endoscopic carpal tunnel release surgery is
      presented, encompassing six endoscopic techniques used to treat carpal tunnel
      syndrome. Since the first report in 1987, 7091 patients have undergone 8068
      operations. The overall success rate has been 96.52%, with a complication rate of
      2.67% and a failure rate of 2.61%. The mean time to return to work in patients
      not receiving Workers' Compensation was 17.8 days, ranging between 10.8 and 22.3
      days. The most common complications were transient paresthesias of the ulnar and
      median nerves. Other complications included superficial palmar arch injuries,
      reflex sympathetic dystrophy, flexor tendon lacerations, and incomplete
      transverse carpal ligament division. In many studies in which open and endoscopic
      techniques were compared, it was reported that patients in the the latter group
      experienced significantly less pain and returned to work and activities of daily
      living earlier. CONCLUSIONS: Success and complication rates of endoscopic carpal
      tunnel release surgery are similar to those for standard open procedures.

PMID- 9576250
TI  - Factors associated with survival in patients with meningioma.
AB  - OBJECT: To explore factors affecting the survival rate in patients with
      meningiomas, the authors used the National Cancer Data Base (NCDB), which
      includes tumors from approximately 1000 hospitals participating in the American
      College of Surgeons tumor registry program. METHODS: Analysis included over 9000
      cases diagnosed from 1985 to 1988 and 1990 to 1992. Survival estimates were
      computed and prognostic factors were identified using a proportional hazards
      model. The overall 5-year survival rate was 69% and it declined with patient age.
      This rate was 81% in patients aged 21 to 64 years and 56% for patients 65 years
      of age or older. When patients were grouped by the histological type of their
      tumors, those with benign tumors had an overall 5-year survival rate of 70%,
      whereas the overall 5-year survival rates in patients with atypical and malignant
      meningiomas were 75% and 55%, respectively. Prognostic factors for benign tumors
      included age at diagnosis, tumor size, whether treated surgically, hospital type,
      and radiation therapy; for malignant tumors, the prognostic factors included: age
      at diagnosis, whether treated surgically, and radiation therapy. These factors
      were statistically significant. The 5-year rate for recurrence of symptoms
      (regardless of the method of treatment) was 19.2% for those with benign tumors
      and 32.4% for those with malignant tumors. In patients whose benign tumor had
      been completely removed, the 5-year rate of tumor recurrence was 20.5%.
      CONCLUSIONS: Although not population-based, the NCDB has the potential for
      providing pertinent information regarding patient characteristics and methods of
      treatment for benign, as well as malignant, brain tumors.

PMID- 9576249
TI  - Catamenial mononeuropathy and radiculopathy: a treatable neuropathic disorder.
AB  - OBJECT: The aim of this study was to investigate the indications and treatment
      options in patients with lower-extremity neuropathies and radiculopathies caused
      by endometriosis. METHODS: The authors identified five patients whose symptoms
      included catamenial pain, weakness, and sensory loss involving the sciatic and
      femoral nerves and multiple lumbosacral nerve roots. Radiographic studies
      supported the diagnosis of catamenial neuropathy or radiculopathy, but definitive
      diagnosis depended on surgical and pathological examination. Treatment of
      symptoms, including physical therapy and a course of antiinflammatory or
      analgesic medication, was not helpful. Patients responded favorably to hormonal
      therapy. Laparoscopy or open exploration for extrapelvic lesions was performed
      for diagnosis or for treatment when hormone therapy failed. Pain and sensory
      symptoms responded well to therapy. Weakness improved, but never recovered
      completely. CONCLUSIONS: Catamenial neuropathy or radiculopathy should be
      considered when evaluating reproductive-age women with recurring focal
      neuropathic leg pain, weakness, and sensory loss.

PMID- 9576251
TI  - Hearing preservation in patients undergoing vestibular schwannoma surgery:
      comparison of middle fossa and retrosigmoid approaches.
AB  - OBJECT: The goal of this retrospective study was to evaluate hearing preservation
      after surgery for vestibular schwannoma in which the middle fossa (MF) or
      retrosigmoid (RS) approaches were used. Hearing preservation in vestibular
      schwannoma surgery can be achieved by using either the MR or RS approach.
      Comparative outcome data between these approaches are lacking, and, as a result,
      selection has generally been determined by the surgeon's preference. METHODS: The
      authors have compared removal of small vestibular schwannomas via MF and RS
      approaches with regard to hearing preservation and facial nerve function. The
      study group was composed of consecutively treated patients with vestibular
      schwannoma, 48 of whom underwent operation via an MF approach and 50 of whom
      underwent the same number of RS operations. Tumors were divided into size-matched
      groups. Hearing results were recorded according to the American Academy of
      Otolaryngology-Head and Neck Surgery criteria, and facial nerve outcome was
      recorded as the House-Brackmann grade. Overall, 26 (52%) of the patients treated
      via the MF approach achieved a Class B or better hearing result compared with
      seven (14%) of the RS group. Some hearing was preserved in 32 (64%) of the
      patients in the MF group and in 17 (34%) of the RS group. The results obtained by
      using the MF approach were superior for intracanalicular tumors (p=0.009, t
      test), and for tumors with a cerebellopontine angle (CPA) component measuring 0.1
      to 1 cm (p=0.006, t-test). For tumors in the CPA that were 1.1 to 2 cm in size,
      our data were inconclusive because of the small sample size. Facial weakness was
      seen more frequently after MF surgery in the early postoperative period, but
      results were equal at 1 year. CONCLUSIONS: The results of this study have
      demonstrated a more favorable hearing outcome for patients with intracanalicular
      tumors and tumors extending up to 1 cm into the CPA that were removed via the MF
      when compared with the RS approach.

PMID- 9576252
TI  - Does the size of intracranial aneurysms change with intracranial pressure?
      Observations based on color "power" transcranial Doppler ultrasound.
AB  - OBJECT: The authors sought to determine whether the increased pulsatility of
      aneurysms, compared with normal intracranial arteries, on color "power"
      transcranial Doppler (TCD) ultrasound was due to a true change in aneurysm size
      and whether aneurysm dimensions change with intracranial pressure (ICP). METHODS:
      The authors studied nine patients who had suffered recent subarachnoid
      hemorrhages complicated by hydrocephalus requiring intraventricular cerebrospinal
      fluid drainage, in whom the presence of an aneurysm was confirmed on angiographic
      examination. Color "power" TCD studies of the intracranial arteries and aneurysm
      were obtained through the temporal bone window before and after insertion of the
      ventricular drain and then at different known ICPs. Of the nine patients studied,
      four were examined both before and after insertion of a ventricular drain. At
      high ICPs, aneurysms appeared very "pulsatile" and the maximum cross-sectional
      area was small, whereas at low ICPs, aneurysms appeared larger and were much less
      pulsatile. The normal arteries did not change significantly in terms of
      pulsatility or maximum cross-sectional area at different levels of ICP.
      CONCLUSIONS: The change in aneurysm size visualized with the aid of color power
      TCD is likely to be real. Aneurysm dimensions vary with ICP levels; the lesions
      are larger and less pulsatile at low ICPs and smaller but more pulsatile at high
      ICPs.

PMID- 9576253
TI  - Terson's syndrome in subarachnoid hemorrhage and severe brain injury accompanied
      by acutely raised intracranial pressure.
AB  - OBJECT: The syndrome of retinal or vitreous hemorrhage in association with
      subarachnoid hemorrhage (SAH) is known as Terson's syndrome. The authors' purpose
      was to determine whether intraocular hemorrhage occurs with similar incidence
      when caused by severe brain injury accompanied by acutely raised intracranial
      pressure (ICP). METHODS: Prospective ophthalmological examination was performed
      in 22 consecutive patients with SAH or severe brain injury and elevated ICP.
      Thirteen patients were admitted for SAH (World Federation of Neurological
      Surgeons Grades II-IV) and nine for severe brain injury (Glasgow Coma Scale
      scores 3-10). Monitoring of ICP was performed at the time of admission via a
      ventricular catheter. Initial ICP exceeded 20 mm Hg in all patients. Indirect
      ophthalmoscopy without induced mydriasis was performed within the 1st week after
      the acute event. Retinal or vitreous hemorrhage was seen in six (46%) of 13
      patients with SAH and in four (44%) of nine patients with severe brain injury.
      Ocular bleeding was found bilaterally in three patients with SAH and in one
      patient with severe brain injury (18%). Six of the 10 patients with Terson's
      syndrome died as a result of their acute event. CONCLUSIONS: The present results
      indicate that Terson's syndrome may be related to acute elevation of ICP,
      independent of its causes, and may occur with similar incidence in patients with
      severe brain injury and those with SAH. Because recognition and treatment of
      Terson's syndrome may prevent visual impairment and associated secondary damage
      to the eye, increased awareness of this entity in all patients with acute raised
      intracranial hypertension is recommended.

PMID- 9576254
TI  - Modified approach for the selective treatment of temporal lobe epilepsy:
      transsylvian-transcisternal mesial en bloc resection.
AB  - OBJECT: The authors propose a novel surgical approach for amygdalohippocampectomy
      (AH) in patients with temporal lobe epilepsy. Via a transsylvian-transcisternal
      route, the parahippocampal gyrus is directly exposed from its medial aspect, thus
      allowing a standardized en bloc resection of the temporomesial epileptogenic
      structures--the amygdala, anterior hippocampus, parahippocampal gyrus, and
      subiculum. Additional anatomical studies have been performed for standardization
      of this approach. METHODS: From 1990 to 1996, 32 patients presenting with
      medically intractable mesial temporal lobe epilepsy underwent AH via the
      transsylvian-transcisternal approach. Preoperative computerized tomography and
      magnetic resonance imaging revealed temporomesial lesions in 16 patients.
      Histopathological examination revealed cavernous malformations in seven patients,
      low-grade astrocytomas in four, hamartomas in three, and gangliogliomas in two
      patients. Specimens obtained in patients with no lesions were diagnosed as
      hippocampal sclerosis in all cases. No patient experienced permanent morbidity.
      Nine percent of the patients developed a temporary partial oculomotor nerve
      palsy. Only one patient developed a postoperative visual field deficit with a
      contralateral quadrantanopsia. With respect to seizure outcome, all patients
      benefited from surgery. At follow-up evaluation (mean 26.4 months), 80% of the
      patients were free from seizures (Engel Class I). Eight patients in this group
      were no longer receiving medication. Seventeen percent had experienced only one
      to several seizures since surgery (Engel Class II) and 3% reported a worthwhile
      improvement (Engel Class III). CONCLUSIONS: In contrast to previously described
      standard techniques for AH, the transsylvian-transcisternal approach presented in
      this study offers improved anatomical orientation and intraoperative control over
      the mesial temporal lobe and preserves the lateral as well as the laterobasal
      temporal lobe.

PMID- 9576255
TI  - Clinical application of functional magnetic resonance imaging in presurgical
      identification of the central sulcus.
AB  - OBJECT: The authors sought to evaluate the advantages and limitations of
      functional magnetic resonance (fMR) imaging when it was used regularly in the
      clinical context to identify the central sulcus. METHODS: A 1.5-tesla MR system
      comprising a spoiled gradient recalled acquisition in the steady-state functional
      sequence and a cross-hand cancellation analysis method were used to evaluate 50
      surgical candidates with centrally located space-occupying lesions in the brain.
      Three-dimensional (3-D) models of the patient's head and brain showing the
      relative position of the tumor and the eloquent cortex were obtained in each
      case. A selective and reproducible focal activation was found, indicating the
      probable central sulcus position in 41 patients (82%). Direct cortical
      stimulation confirmed the fMR findings in 100% of 22 intraoperatively assessed
      patients. Failure to identify the central sulcus occurred in 18% of cases and was
      mainly a consequence of intrinsic damage in the primary sensorimotor region that
      resulted in severe hand paresis. CONCLUSIONS: Although specific factors were
      identified that contributed to reduced sensitivity of fMR imaging in the clinical
      context, the present study supports functional assessment and 3-D representation
      of specific surgical situations as generally feasible in common practice.

PMID- 9576256
TI  - Selective intraarterial gene delivery into a canine meningioma.
AB  - OBJECT: The goal of this study was to evaluate gene delivery to a benign brain
      tumor. METHODS: A recombinant adenovirus vector bearing the Escherichia coli beta
      galactosidase reporter gene was selectively injected into the vascular supply of
      a spontaneously occurring canine olfactory groove meningioma. The tumor and a
      small amount of peritumoral brain tissue were removed 5 days after viral
      injection and stained with X-Gal to assess gene delivery. The authors noted
      significant beta-galactosidase gene expression by the tumor, but not by
      surrounding brain tissue. No obvious viral-related cytotoxicity was noted.
      CONCLUSIONS: The authors found that meningiomas can be successfully transduced by
      adenovirus vectors by using endovascular techniques.

PMID- 9576257
TI  - The presence of 4-hydroxynonenal/protein complex as an indicator of oxidative
      stress after experimental spinal cord contusion in a rat model.
AB  - OBJECT: The authors tested the hypothesis that breach of the blood-spinal cord
      barrier (BSCB) will produce evidence of oxidative stress and that a similar
      staining pattern will be seen between 4-hydroxynonenal (HNE)/protein complexes
      and extravasated immunoglobulin G (IgG). METHODS: Adult female Fischer 344 rats,
      each weighing 200 to 225 g, were subjected to a spinal cord contusion at T-10 by
      means of a weight-drop device. Spinal cord tissue was assessed for oxidative
      stress by localizing extravasated plasma contents with a monoclonal antibody for
      rat IgG and protein conjugation with HNE, which is an aldehyde byproduct of lipid
      peroxidation. The animals were killed at 1 and 6 hours, and 1, 2, and 7 days
      after surgery. Maximum HNE/protein staining was observed at 2 days postinjury,
      and HNE/protein and IgG manifested similar staining patterns. Analysis revealed a
      graduated but asymmetrical rostral-caudal response relative to the T-10 injury
      site. Both HNE/protein complex and IgG staining revealed that the caudal levels T
      11 and T-12 stained significantly more intensely than the rostral levels T-9 and
      T-8, respectively. A higher percentage of neurons positive for HNE/protein
      immunostaining was observed in spinal cord levels caudal to the injury site
      compared with equidistant rostral regions. Protein dot-blot assays also revealed
      a similar asymmetrical rostral-caudal HNE/protein content. To analyze the timing
      of the BSCB breach, another group of animals received identical contusions, and
      horseradish peroxidase (HRP) was injected 10 minutes before or at various times
      after injury (1, 3, and 6 hours, and 1, 2, and 7 days). Maximum HRP permeability
      was seen immediately after injury, with a significant decrease occurring by 1
      hour and a return to control levels by 2 days posttrauma. CONCLUSIONS: Data from
      this study indicate possible compromise of neuronal, axonal, glial, and synaptic
      function after trauma, which may be a factor in motor deficits seen in animals
      after spinal cord contusion. The colocalization of the IgG stain with the
      HNE/protein stain is consistent with the hypothesis of a mutual cause-effect
      relationship between BSCB and oxidative stress in central nervous system trauma.

PMID- 9576259
TI  - Spinal meningeal melanocytoma presenting with superficial siderosis of the
      central nervous system. Case report and review of the literature.
AB  - Meningeal melanocytoma is a benign melanocytic tumor that originates most
      frequently from the melanocytes in the posterior fossa or along the spinal cord.
      This tumor generally occurs as an extraaxial mass that compresses adjacent neural
      structures to produce various neurological signs. The authors describe an unusual
      case in which a patient with a meningeal melanocytoma located at the thoracic
      spinal cord presented with superficial siderosis of the central nervous system
      (CNS). Extensive neuroradiological studies identified the presence of a spinal
      cord tumor, and postsurgical histological examination revealed the meningeal
      melanocytoma as a bleeding source. After surgery, lumbar puncture demonstrated
      normalization of the patient's cerebrospinal fluid; however, no neurological
      improvement occurred. The neurological deficits seem irreversible. Meningeal
      melanocytoma is biologically benign and can be cured by complete surgical
      resection; therefore, this tumor should be included in the differential diagnosis
      of pigmented lesions of the CNS. The authors reviewed 14 cases of well-documented
      meningeal melanocytoma in the literature and discuss the clinical, radiological,
      and pathological features of the present case to emphasize the importance of
      early diagnosis and identification of the source of bleeding in patients with
      superficial siderosis.

PMID- 9576258
TI  - Antagonist effect of insulin-like growth factor I on protein kinase inhibitor
      mediated apoptosis in human glioblastoma cells in association with bcl-2 and bcl
      xL.
AB  - OBJECT: Tamoxifen (TAM) has been found to be effective in inhibiting
      proliferation of glioblastoma cells in vitro, but clinical studies have been
      disappointing. The purpose of this study was to determine whether insulin-like
      growth factor I (IGF-I), a potential autocrine/paracrine mitogen produced by
      glioblastomas, interferes with the antimitogenic actions of TAM. METHODS: Human
      glioblastoma cells were treated with or without TAM and/or IGF-I in vitro and
      evaluated for: viability by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol
      tetrazolium bromide cleavage assay; apoptosis by histochemical analysis of
      nuclear morphology and 3'-OH DNA fragments; and expression of the IGF-I receptor,
      and the bcl-2, bcl-xL, and bax proteins by immunoblot analysis. In addition, p53
      status was determined by DNA sequencing and by transient transfection with
      luciferase reporter plasmids containing wild-type or mutant p53. Results
      indicated that after 72 hours of exposure to 2 mg/ml TAM in vitro, 56.3% of WITG3
      and 43.8% of U87-MG glioblastoma cells contained apoptotic nuclei (p < 0.01
      compared with untreated cells). Apoptosis was independent of the presence of p53
      because the WITG3 cells, in contrast to the U87-MG cells, expressed a mutant,
      nonfunctional p53. The WITG3 cells expressed IGF-I receptor proteins and
      demonstrated IGF-I binding. Exogenous IGF-I stimulated WITG3 cell proliferation
      and significantly (p < 0.05) antagonized the cytotoxic effects of TAM in a dose
      dependent fashion; IGF-I, but not TAM, enhanced expression of bcl-2 and bcl-xL
      proteins; however, bax protein expression was unchanged by either treatment.
      CONCLUSIONS: Because many gliomas secrete large amounts of IGF-I in
      autocrine/paracrine growth pathways, these data may, in part, explain the failure
      of TAM to achieve clinical results as dramatic as those in vitro.

PMID- 9576260
TI  - Abscess formation within a parasagittal meningioma. Case report.
AB  - The authors present the case of a 78-year-old woman who developed right lower
      extremity paralysis after a focal seizure. Neuroradiological studies revealed a
      small parasagittal meningioma, which at the time of resection was found to
      contain a bacterial intratumoral abscess secondary to Proteus mirabilis. This is
      only the second reported case of intratumoral abscess formation in a meningioma
      and the first such occurrence to be reported in an otherwise healthy,
      immunocompetent individual.

PMID- 9576261
TI  - Thoracoscopic microsurgical excision of a thoracic schwannoma. Case report.
AB  - A 6-cm-diameter schwannoma located at T-2 was resected completely by using
      transthoracic microsurgical endoscopy. The partially cystic tumor widened the
      neural foramen and extended into the apex of the right thoracic cavity but did
      not extend intradurally. The tumor was accessed by means of three 15-mm incisions
      made in the intercostal spaces. The operative blood loss was only 200 ml, and
      there were no complications. The patient was discharged on the 2nd postoperative
      day and returned to full activity 1 week after surgery. Thoracoscopy provides an
      excellent alternative to thoracotomy for peripheral thoracic nerve sheath tumors
      that originate within the neural foramen or more distally along the intercostal
      nerves within the thorax. An anterior approach is required for intrathoracic
      tumors but is not suited for intradural tumors. An open posterior or
      posterolateral approach to the thoracic spine is required for intradural tumors
      to allow the dura to be closed adequately.

PMID- 9576263
TI  - Spinal epidural vascular malformation presenting in association with a
      spontaneously resolved acute epidural hematoma. Case report.
AB  - A 16-year-old boy developed acute neck pain and severe quadriparesis after mild
      rotatory movement of his neck. Magnetic resonance imaging revealed a cervical
      epidural hematoma that resolved spontaneously within a few days. Vertebral
      angiography demonstrated a small vascular malformation in the upper cervical
      epidural space. The vascular mass on the dural surface was totally resected and
      confirmed to be an arteriovenous malformation. This case represents the
      importance of including routine angiography in designing therapeutic strategy for
      cases of spinal epidural hematoma with spontaneous resolution.

PMID- 9576262
TI  - Spinal epidural cavernous hemangiomas. Report of three cases and review of the
      literature.
AB  - Epidural cavernous hemangiomas are increasingly identified as a cause of acute or
      chronic progressive spinal cord syndrome and local back pain or radiculopathy.
      The authors present three cases of spinal epidural cavernous hemangiomas
      manifesting as spinal cord syndrome, thoracic radiculopathy, and lumbar
      radiculopathy. Based on the imaging characteristics of these three cases and a
      review of the literature, the clinical signs and symptoms and their implications,
      the role of preoperative neuroradiological diagnosis, and the need for complete
      surgical resection are discussed. Epidural cavernous hemangiomas display
      consistent magnetic resonance imaging properties: T1-weighted images most
      commonly show a homogeneous signal intensity similar to those of spinal cord and
      muscle, and contrast enhancement is homogeneous or slightly heterogeneous. On T2
      weighted images the signal of the lesion is consistently high and slightly less
      intense than that of cerebrospinal fluid. Frequently, the lesion is characterized
      by its extension through the intervertebral foramen. Awareness of these
      characteristics facilitates diagnosis and treatment of the lesions. Despite the
      risk of bleeding, in all three cases complete surgical excision was achieved.

PMID- 9576264
TI  - Spinal dural enhancement on magnetic resonance imaging associated with
      spontaneous intracranial hypotension. Report of three cases and review of the
      literature.
AB  - This report offers a description of typical changes seen on gadolinium-enhanced
      magnetic resonance (MR) imaging of the entire spine that indicate spontaneous
      intracranial hypotension (SIH). To the authors' knowledge, this is the first
      report of its kind. They describe three cases of SIH that were accompanied by
      dural enhancement throughout the neuraxis on imaging, with the evolution of
      associated subdural and epidural fluid collections in the spine. Recognition of
      this disorder is important to be able to distinguish it from an infectious or
      neoplastic process in which surgical intervention might be warranted. Evaluation
      using gadolinium-enhanced cranial and spinal MR imaging in patients with postural
      headaches and an (111)In-labeled cerebrospinal fluid leak study are discussed.
      Treatment with an epidural blood patch is shown to be particularly effective,
      with resolution of the radiological and clinical findings.

PMID- 9576266
TI  - Tumor devascularization by intratumoral ethanol injection during surgery.
      Technical note.
AB  - Preoperative reduction in tumor vascularity has been accomplished previously by
      selective catheterization of tumor vessels and delivery of occlusive materials.
      The results of percutaneous infusion of vertebral hemangiomas and other vascular
      lesions led the authors to speculate that rapid devascularization of tumors by
      direct injection of ethanol (ETOH) could be used to reduce bleeding and
      facilitate resection during surgery. Thus, the use of intratumoral injection of
      ETOH and its effects on tumor hemostasis and resectability were examined. Four
      patients received direct injection of ETOH into either a spinal epidural (two
      renal cell carcinomas and one rhabdomyosarcoma) or a large cerebellar neoplasm
      (hemangioblastoma). Intraoperative perfusion of the tumors with ETOH produced
      immediate blanching and devascularization and enhanced visualization and
      resection. Incremental tumor devascularization is achieved by careful injection
      of small amounts of ETOH directly into the lesion, producing immediate and
      complete regional tumor devascularization. Use of this technique reduces
      intratumoral bleeding and enhances the ease and effectiveness of resection.

PMID- 9576265
TI  - Thrombolysis and angioplasty for acute occlusion of intracranial vertebrobasilar
      arteries. Report of three cases.
AB  - Three cases of intracranial vertebrobasilar occlusion were successfully treated
      in the acute stage by thrombolysis and angioplasty. All three patients were
      admitted to the hospital because of consciousness disturbance and other brainstem
      signs. Initial angiography revealed intracranial vertebrobasilar occlusions. At
      first, a microcatheter was introduced into the distal site of the occlusion and
      thrombolysis was attempted by using urokinase. Recanalization was achieved in all
      cases but severe stenosis of the intracranial vertebral and basilar arteries was
      found. The recanalization was followed by transluminal balloon angioplasty and
      the stenosis was successfully resolved. Marked neurological improvement was
      achieved in each case. Follow-up cerebral angiography demonstrated sufficient
      patency at the angioplasty site after 3 to 6 months. Residual severe stenosis of
      vertebrobasilar arteries after thrombolytic therapy carries the possibility of
      reocclusion. Combining angioplasty with thrombolysis to avoid rethrombosis and
      obtain sufficient distal blood flow is of significant benefit in treating
      vertebrobasilar occlusion.

PMID- 9576267
TI  - High-flow bypass using nonocclusive excimer laser-assisted end-to-side
      anastomosis of the external carotid artery to the P1 segment of the posterior
      cerebral artery via the sylvian route. Technical note.
AB  - In a patient with a giant aneurysm of the basilar artery trunk, a vein graft was
      interposed between the external carotid artery in the neck and the P1 segment of
      the posterior cerebral artery. Balloon occlusion of both vertebral arteries was
      performed 3 days later. The sylvian route was used for the grafting procedure and
      the connection to the posterior cerebral artery was made by using the excimer
      laser-assisted nonocclusive anastomosis technique.

PMID- 9576268
TI  - Magnetic resonance image of postcraniotomy retained cotton or rayon. Case
      illustration.

PMID- 9576269
TI  - Hemorrhagic skull pseudotumor associated with idiopathic thrombocytopenic
      purpura. Case illustration.

PMID- 9576270
TI  - Abdominal pseudohernia following intradural tumor excision. Case illustration.

PMID- 9576271
TI  - Treatment of vasospasm.

PMID- 9576272
TI  - Arteriovenous malformations and vasospasm.

PMID- 9576273
TI  - Diagnosis of ganglioglioma.

PMID- 9576274
TI  - Chronic subdural hematoma.

PMID- 9576276
TI  - Total pelvic exenteration.

PMID- 9576275
TI  - Hydroxyurea for treatment of meningioma.

PMID- 9576277
TI  - Revision of TNM classification for oropharyngeal carcinoma.

PMID- 9576278
TI  - Clinical staging of oropharyngeal carcinoma: a critical evaluation of a new stage
      grouping proposal.
AB  - BACKGROUND: An alternative to the International Union Against Cancer/American
      Joint Committee on Cancer (UICC/AJCC) stage grouping system was proposed for
      patients with oropharyngeal carcinoma by Hart et al. (1995) on behalf of the
      Dutch Head and Neck Oncology Cooperative Group. The system was created by
      regrouping the T, N, and M categories without redefining the categories
      themselves. METHODS: Data related to epidemiology, treatment, and survival from
      224 previously untreated patients with oropharyngeal carcinoma were analyzed.
      Staging was performed according to the 1992 UICC/AJCC criteria and according to
      the proposed stage grouping system. Kaplan-Meier estimates of overall survival
      were compared for both staging systems; and in a Cox proportional hazards
      regression analysis, the influence of the variables age, gender, subsite and side
      of tumor location, histopathologic grade, form of treatment, and stage
      distribution (according to 1992 UICC criteria and that proposed by Hart et al.)
      on overall survival was determined. RESULTS: The proposed staging system showed a
      more balanced distribution of patients (16% in Stage I, 37% in Stage II, 14% in
      Stage III, and 33% in Stage IV compared with 5% in Stage I, 7% in Stage II, 21%
      in Stage III, and 67% in Stage IV according to UICC/AJCC 1992 staging).
      Furthermore, the proposed staging system showed better prognostic discrimination
      for overall survival (5-year survival rates according to the staging system of
      Hart et al. were 59% in Stage I, 31% in Stage II, 28% in Stage III, and 16% in
      Stage IV, vs. 61% in Stage I, 59% in Stage II, 32% in Stage III, and 24% in Stage
      IV according to UICC/AJCC 1992 staging). CONCLUSIONS: The results are in
      concordance with the results published by the Dutch Head and Neck Oncology
      Cooperative Group. It is possible to improve the current staging system by
      regrouping the T, N, and M categories. [See editorial on pages 1611-2, this
      issue.]

PMID- 9576279
TI  - Phenotype 2 of deoxyribonuclease I may be used as a risk factor for gastric
      carcinoma.
AB  - BACKGROUND: Human deoxyribonuclease I (DNase I) (EC3.1.21.1) is one of the
      candidate nucleases that acts in mammalian cells during apoptosis. Genetic
      polymorphism of DNase I has been classified into 15 phenotypes controlled by 5
      autosomal codominant alleles. The purpose of this study was to determine whether
      DNase I polymorphism is closely related to the incidence of gastric carcinoma.
      METHODS: The phenotype distribution was examined using urine samples obtained
      from unrelated Japanese patients with gastric carcinoma (n = 97) and benign
      gastric diseases (n = 76). Phenotyping was performed using isoelectric focusing
      electrophoresis in thin polyacrylamide gel and immunoblotting with an antihuman
      DNase I antibody. RESULTS: A close statistical association was found between
      patients with gastric carcinoma and a high frequency of DNase I phenotype 2.
      However, there was no significant difference in the phenotype distribution
      between the group of patients with benign gastric diseases and the controls.
      CONCLUSIONS: The findings of the current study suggest that DNase I phenotype 2
      may be a marker for gastric carcinoma. Therefore, compared with other phenotypes,
      DNase I phenotype 2 may have potential for identifying patients who are at risk
      of harboring or developing gastric carcinoma.

PMID- 9576280
TI  - High expression of thymidylate synthase is associated with the drug resistance of
      gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy.
AB  - BACKGROUND: In the past 4 years, the weekly 24-hour infusion of high dose 5
      fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced
      gastric carcinoma has been prospectively studied at the authors' institution.
      This has enabled them to explore the possibility that the level of expression of
      thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug
      sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS: To be
      eligible for this study, patients were required to have received high dose 5-FU
      and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and
      leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma
      tissues for immunohistochemical study. TS106 monoclonal antibody was used to
      detect the expression of TS. A visual scoring system, which ranged from 0 to 3+,
      was adopted by 2 independent pathologists to semiquantitate the intensity of TS
      expression. RESULTS: Between 1993 and 1996, a total of 30 patients, 18 men and 12
      women, with a median age of 61.5 years, were enrolled. Of these patients, 16
      (53.3%) and 14 (46.7%) had high and low expression of TS, respectively. Two of
      the 16 patients (12.5%) with high expression of TS and 13 of the 14 patients
      (92.9%) with low expression of TS responded to chemotherapy (P < 0.001, chi
      square test). The median overall survival was 10 months for patients with low TS
      expression and 4 months for patients with high TS expression (P < 0.01, log rank
      test). CONCLUSIONS: The data from this study suggest that the expression of TS,
      as determined by immunohistochemistry, is a relatively reliable indicator of
      whether 5-FU should be used in the treatment of patients with gastric carcinoma.

PMID- 9576281
TI  - A cost-effectiveness analysis of colorectal screening of hereditary nonpolyposis
      colorectal carcinoma gene carriers.
AB  - BACKGROUND: It has been estimated that the prevalence of carriers of a mutated
      mismatch repair (MMR) gene among the general population in Western countries is
      between 5 and 50 per 10,000. These carriers have a risk of >85% of developing
      colorectal carcinoma (CRC) and therefore need careful follow-up. The objective of
      this study was to analyze the cost-effectiveness of CRC surveillance of carriers
      of a mutated MMR gene. METHODS: The authors constructed a model to estimate the
      potential health effects (life expectancy) and healthcare costs of two
      strategies: 1) surveillance, with colonoscopy every 2-3 years, and 2) no CRC
      surveillance. Estimates of the lifetime risk of developing CRC and the stage
      distribution of CRC for symptomatic patients were derived from the Dutch
      hereditary nonpolyposis colorectal carcinoma (HNPCC) registry. The CRC stage
      specific relative survival rates and the effectiveness of surveillance in
      preventing or detecting cancer early were based on Finnish studies. The costs of
      surveillance and treatment were derived from recent American studies. RESULTS:
      The results showed that 1) surveillance of gene carriers led to an increase in
      life expectancy of 7 years, and 2) the costs of surveillance under a wide range
      of assumptions are less than the costs of no CRC surveillance. CONCLUSIONS: CRC
      surveillance of HNPCC gene carriers appears to be effective and considerably less
      costly than no CRC surveillance and therefore deserves to be supported by
      governmental agencies and health insurance organizations.

PMID- 9576282
TI  - Needle tract implantation of hepatocellular carcinoma after percutaneous ethanol
      injection.
AB  - BACKGROUND: Percutaneous ethanol injection (PEI) therapy currently is widely used
      for small hepatocellular carcinoma (HCC). However, only limited information is
      available regarding needle tract implantation after PEI treatment. METHODS:
      Records of HCC patients who underwent PEI between March 1990 and April 1997 at
      the National Cancer Center Hospital (n = 177) were reviewed to clarify the
      incidence, risk factors, and outcome of needle tract implantation of HCC.
      RESULTS: PEI was performed for 348 HCC patients with a median tumor size of 20
      mm. Needle tract implantation was found in 4 patients (10, 13, 15, and 46 months,
      respectively, after PEI). The size of the PEI-treated HCC tumors in these
      patients was 20, 27, 28, and 30 mm, respectively, in greatest dimension. All
      tumors were enhanced in the early phase on dynamic computed tomography (CT), and
      were found to have moderate tumor cell differentiation on biopsied specimens. Of
      the four implanted tumors, three were resected and the remaining tumor was
      treated with extrabeam radiotherapy. At last follow-up, 2 of the 4 patients had
      died (1 of variceal bleeding 60 months after PEI and the other from cancer 61
      months after PEI) and 2 were still alive (14 and 20 months, respectively, after
      PEI) with no evidence of active tumor. CONCLUSIONS: Needle tract implantation
      after PEI is not unusual, especially when HCC tumors are > or =2 cm in greatest
      dimension, enhanced in the early phase on dynamic CT, and/or moderately
      differentiated on biopsied specimens.

PMID- 9576283
TI  - The usefulness of determining des-gamma-carboxy prothrombin by sensitive enzyme
      immunoassay in the early diagnosis of patients with hepatocellular carcinoma.
AB  - BACKGROUND: Measurements of serum concentrations of des-gamma-carboxy prothrombin
      (DCP) are widely used for diagnosing hepatocellular carcinoma (HCC). However, the
      DCP is not always sensitive enough to detect small HCCs. In the current study,
      the authors investigated the usefulness of DCP in the early diagnosis of HCC,
      using a more sensitive enzyme immunoassay than is conventionally employed.
      METHODS: The authors examined 148 serum samples with DCP concentrations from a
      conventional assay of less than 100 mAU (arbitrary unit)/mL from 91 patients with
      HCC and 57 with cirrhosis. DCP concentrations were determined by a more sensitive
      enzyme immunoassay (ED-036 kit, Eisai Laboratory, Tokyo, Japan) with a minimal
      detection level of 10 mAU/mL. Ninety-one HCC patients had 43 solitary small HCCs
      (with a greatest dimension of less than 2 cm). Of these 43 HCCs, 12 were well
      differentiated. RESULTS: The mean serum concentration of DCP in HCC (48.3 +/-
      24.3, mean +/- standard deviation [SD]) was higher than in cirrhosis (20.3 +/-
      10.3); this difference was statistically significant. When the tentative cutoff
      level of 40 mAU/mL (almost corresponding to the mean value + 2SD in patients with
      cirrhosis) was used as the level of discriminating HCC from cirrhosis, 62% of
      patients (56 of 91) with HCC had DCP values above this level (sensitivity).
      However, only three patients with cirrhosis had higher DCP levels. Thus, the
      specificity of this test was 95% (54 of 57 patients). The total accuracy was 74%
      (56 + 54/91 + 57). Twenty-three of 43 solitary small HCCs (53%) had DCP values
      above the cutoff level. Furthermore, 7 of 12 (58%) small, well-differentiated
      HCCs less than 2 cm in greatest dimension had higher DCP values. CONCLUSIONS: The
      results of this study indicate that DCP determination by sensitive enzyme
      immunoassay is useful in the early diagnosis of HCC because a high specificity is
      maintained.

PMID- 9576284
TI  - Pancreatic carcinoma: correlation between E-cadherin and alpha-catenin expression
      status and liver metastasis.
AB  - BACKGROUND: Dysfunction of the E-cadherin/catenin-mediated cell-cell adhesion
      system has been associated with invasiveness and poor differentiation of human
      carcinomas. However, its importance in the genesis of liver metastasis has not
      been examined sufficiently. METHODS: A series of 26 primary pancreatic carcinomas
      and the concomitant liver metastases from 15 of them, obtained at autopsy, were
      analyzed for E-cadherin and alpha-catenin protein expression by
      immunohistochemistry. RESULTS: Both E-cadherin and alpha-catenin expression were
      preserved in 15 (58%) and reduced in 11 (32%) of the 26 primary pancreatic
      carcinomas. In the former 15 primaries, carcinoma cells were attached to each
      other tightly, whereas the latter 11 primaries showed isolated or loosely
      connected attachments. The metastatic ratio was higher in tumors exhibiting tight
      adhesion than in those with loose adhesion: 73% and 36%, respectively (P =
      0.059). E-cadherin and alpha-catenin expression patterns in liver metastases
      basically followed those in the corresponding primaries (P < 0.01). CONCLUSIONS:
      Reduced E-cadherin and alpha-catenin expression in primary pancreatic carcinoma
      has no significant predictive value regarding the presence of liver metastasis.
      Rather, there is a greater tendency for liver metastasis in cases in which the
      integrity of the E-cadherin/catenin-mediated cell-cell adhesion system is intact.

PMID- 9576285
TI  - Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal
      loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary
      osteochondromas.
AB  - BACKGROUND: Osteochondroma most frequently arises sporadically and as a solitary
      lesion, but also may arise as multiple lesions characterizing the autosomal
      dominant disorder hereditary multiple exostoses (HME) and the contiguous gene
      syndromes Langer-Giedion and DEFECT-11 syndromes. HME is genetically
      heterogeneous with association of three loci including 8q24.1 (EXT1), 11p11-12
      (EXT2), and 19p (EXT3). Constitutional chromosomal microdeletions of 8q24.1 and
      11p11-12 are features of the Langer-Giedion and DEFECT-11 syndromes,
      respectively. Cytogenetic studies of osteochondroma are rare. METHODS:
      Cytogenetic analysis was performed on 34 osteochondroma specimens from 22
      patients with sporadic lesions and 4 patients with HME utilizing standard
      methodologies. Fluorescence in situ hybridization with chromosome specific probes
      was performed on three cases to define structural rearrangements further.
      RESULTS: Clonal abnormalities were detected in ten cases. Notably, deletion of
      11p11-13 was observed in one case (a sporadic tumor) and loss or rearrangement of
      8q22-24.1 in eight cases (seven sporadic and one hereditary tumor). CONCLUSIONS:
      These findings: 1) confirm previous observations of 8q24.1 karyotypic anomalies
      in sporadic osteochondroma, 2) reveal the presence of somatic chromosomal
      anomalies in hereditary osteochondromata, 3) suggest that similar to hereditary
      lesions, sporadic osteochondromas also are genetically heterogeneic (involvement
      of both 8q24.1 and 11p11-12), and 4) support the hypothesis that loss or mutation
      of EXT1 and EXT2, two putative tumor suppressor genes, may be important in the
      pathogenesis of sporadic as well as hereditary osteochondromata.

PMID- 9576286
TI  - Primary staging and follow-up of high risk melanoma patients with whole-body 18F
      fluorodeoxyglucose positron emission tomography: results of a prospective study
      of 100 patients.
AB  - BACKGROUND: Positron emission tomography (PET) has been retrospectively reported
      to be a sensitive method for detecting malignant melanoma metastases. METHODS:
      One hundred consecutive patients with high risk melanoma (tumor thickness > 1.5
      mm) were prospectively evaluated (52 at primary diagnosis, comprising Group A,
      and 48 during follow-up, comprising Group B) by whole-body PET and conventional
      diagnostics (CD). RESULTS: In Group A, the sensitivity of PET was 100% and the
      specificity was 94%, whereas CD did not identify any of the 9 lymph node
      metastases and demonstrated a lower specificity (80%). In Group B, 121 lesions
      were detected, 111 by PET and 69 by conventional imaging. On the basis of
      patients, the sensitivity, specificity, and accuracy of PET were 100%, 95.5%, and
      97.9%, respectively (91.8%, 94.4%, and 92.1%, respectively, on the basis of
      single metastases). Prospectively, CD did not identify all patients with
      progression (sensitivity, 84.6%) and detected significantly fewer metastases
      (sensitivity, 57.5%) with much lower specificity (68.2% on the basis of patients,
      45% on the basis of single lesions); therefore, the accuracy of CD was 77.1% on
      the basis of patients and only 55.7% on the basis of single metastases. Results
      also depended on specific sites: while PET yielded a higher sensitivity in
      detecting cervical metastases (100% vs. 66.6%) and abdominal metastases (100% vs.
      26.6%), computed tomography proved to be superior in detecting small lung
      metastases (87% vs. 69.6%). CONCLUSIONS: PET is a highly sensitive and specific
      technique for melanoma staging. With the exception of the brain, one single whole
      body 18F-fluorodeoxyglucose-PET scan could replace the standard battery of
      imaging tests currently performed on high risk melanoma patients.

PMID- 9576287
TI  - The risk of subsequent primary carcinoma of the pancreas in patients with
      cutaneous malignant melanoma.
AB  - BACKGROUND: Carcinoma of the pancreas is the fifth leading cancer in the U.S. and
      has the poorest survival rate of the major malignancies. Recent studies have
      reported an increased risk of carcinoma of the pancreas in malignant melanoma
      prone kindreds and have suggested a link between malignant melanoma and pancreas
      carcinoma and mutations in the p16INK4 gene. This study evaluates the risk of
      carcinoma of the pancreas in a population-based cohort of patients with malignant
      melanoma. METHODS: The malignant melanoma patients were identified from the
      Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer
      Institute. The cohort was followed within the SEER system to ascertain the
      occurrence of subsequent microscopically confirmed primary carcinoma of the
      pancreas from January 1973 through December 1993. The time of follow-up was
      expressed as person-years of observation. Standardized incidence ratios (SIR) and
      95% confidence intervals (95% CI) were calculated. RESULTS: There were 43,781
      malignant melanoma patients providing 263,528 person-years of follow-up. A nearly
      2-fold increased risk of subsequent carcinoma of the pancreas in patients
      diagnosed with malignant melanoma before age 50 years was observed (SIR = 1.76;
      95% CI = 0.80-3.34) and the greatest estimated risk occurred in young white
      females (SIR = 2.27; 95% CI = 0.73-5.30). CONCLUSIONS: These results provide some
      evidence in support of observations in recent studies that not only a family
      history of malignant melanoma but also malignant melanoma diagnosed at an early
      age may be associated with the subsequent development of carcinoma of the
      pancreas. Further research with larger numbers of melanoma patients is necessary
      to explore these potential associations.

PMID- 9576288
TI  - Interferon-alpha and chemohormonal therapy for patients with advanced melanoma:
      final results of a phase I-II study of the Cancer Biotherapy Research Group and
      the Mid-Atlantic Oncology Program.
AB  - BACKGROUND: The treatment of metastatic melanoma remains unsatisfactory despite
      encouraging results with biotherapy and combination chemotherapy. Combining these
      two modalities may improve outcomes for such patients. METHODS: Patients who were
      eligible for this study had metastatic melanoma and were in good medical
      condition. The following regimen was used: dacarbazine 220 mg/m2 and cisplatin 25
      mg/m2 administered intravenously (i.v.) daily x 3 days every 3 weeks, carmustine
      150 mg/m2 i.v. every 6 weeks, tamoxifen 10 mg administered orally twice a day,
      and interferon-alpha2b 3.0 thousandths of an International Unit (mIU)/m2
      administered subcutaneously on Days 1, 3, and 5 of each week a patient was on
      study. Patients were analyzed for toxicity, tumor response, and survival. Because
      of severe toxicity, partway through the trial the regimen was modified as
      follows: dacarbazine and cisplatin were given at the same dose every 4 weeks, and
      carmustine was reduced to 100 mg/m2 every 8 weeks. RESULTS: Forty-two patients
      with a median age of 61 years were enrolled. Twenty had liver metastases and 18
      had lung metastases. Forty patients were evaluable for toxicity, 17 at the
      original dose and 23 at the new dose; of these, 35 were evaluable for response.
      Hematologic toxicity was severe at the original dose: 10 patients had a nadir <
      500/microL, 10 had platelets < 25,000/microL, and 2 discontinued treatment
      because of toxicity. At the reduced dose, 5 had a nadir absolute neutrophil count
      < 500, and 10 had platelets < 25,000. Of the 35 patients evaluable for response,
      there were 10 partial responses (29%) and 2 minimal responses. Median duration of
      disease control was 4 months. Median survival was 8.9 months. One partial and one
      minimal responder were removed from the study because they experienced toxicity
      while still responding. CONCLUSIONS: The addition of interferon-alpha to this
      chemohormonal therapy regimen greatly increased toxicity without improving the
      response rate or survival for patients with metastatic melanoma.

PMID- 9576289
TI  - Hot flashes in postmenopausal women treated for breast carcinoma: prevalence,
      severity, correlates, management, and relation to quality of life.
AB  - BACKGROUND: Research on hot flashes (HFs) after the diagnosis and treatment of
      breast carcinoma (BC) is scarce. To our knowledge, this research represents the
      second study of HF prevalence and severity in women with BC and the first study
      of 1) correlates of HF prevalence and severity, 2) use of HF management
      strategies, and 3) the relation between HFs and quality of life (QOL) among women
      with BC. METHODS: Eligible women (n = 136) participated in structured telephone
      interviews. RESULTS: Of the 114 postmenopausal women interviewed, 65% reported
      HFs, with 59% of women with HFs (n = 74) rating the symptom as severe.
      Multivariate analysis revealed that 1) HFs were most common in women with a high
      school education or less and those who were younger at diagnosis and 2) HFs were
      most severe in women with a higher body mass index, those who were younger at
      diagnosis, and those receiving tamoxifen. Among women with HFs, 37% were not
      using any HF management strategies and 63% expressed interest in learning more
      regarding > or = 1 strategy. HFs marginally were related to decreased mental and
      physical QOL using the SF-12 Health Survey (P < 0.10). CONCLUSIONS: The results
      of the current study significantly contribute to knowledge regarding HFs in women
      with BC and support the need for carefully controlled clinical trials evaluating
      interventions for relieving HFs in this population.

PMID- 9576290
TI  - A comparison of screening mammography results from programs for women of
      different socioeconomic status.
AB  - BACKGROUND: The ability of screening mammography programs serving women of
      different socioeconomic status (SES) to diagnose early stage breast carcinoma in
      a comparably effective fashion has been questioned. METHODS: Results of screening
      50,653 women of lower SES were compared with those of screening 45,923 more
      socioeconomically advantaged women during the same period in New York State.
      Results were compared with those reported for the general population to the New
      York State cancer registry. RESULTS: Additional workup was required for
      approximately 12% of the women in each group. Although more women of lower SES
      underwent biopsy, the positive predictive value of a biopsy recommendation was
      almost the same for the two populations (27% for women of higher SES vs. 25% for
      women of lower SES). Among women with breast carcinoma, ductal carcinoma in situ
      was diagnosed in 27% of more affluent women and 15% of women of lower SES, a
      considerable improvement from the 10% rate of diagnosis in the general population
      in New York State. Minimal cancers accounted for 54% of those diagnosed in more
      affluent women and at least 31% of those diagnosed in women of lower SES.
      CONCLUSIONS: Screening mammography programs can be effective for women of lower
      SES and can be conducted as efficiently as they are for more affluent women.
      Differences in diagnosis of small cancers in the two groups reported in this
      article may reflect differences in age and patterns of prior screening experience
      in the two populations.

PMID- 9576291
TI  - The incidence of subsequent endometrial carcinoma with tamoxifen use in patients
      with primary breast carcinoma.
AB  - BACKGROUND: Tamoxifen commonly is used as adjuvant therapy for all stages of
      breast carcinoma. However, several studies have suggested an association between
      the use of tamoxifen in breast carcinoma patients and the subsequent development
      of endometrial carcinoma. The objective of this study was to determine the
      relation between long term tamoxifen usage and the risk of endometrial carcinoma
      in patients with breast carcinoma and to determine whether the increase in the
      cumulative incidence of endometrial carcinoma observed in previous studies is a
      true increase. METHODS: Eight hundred and twenty-five patients with primary
      breast carcinoma who underwent annual gynecologic examination and cancer
      screening were reviewed. None of the patients had undergone hysterectomy or
      received any prior estrogen replacement therapy. These patients underwent a
      pelvic examination and cytologic and/or histologic screening of the cervix and
      endometrium every year even if they had no gynecologic symptoms. The dose of
      tamoxifen, length of tamoxifen treatment, and potential confounding variables
      were recorded. The relative risk of subsequent endometrial carcinoma in patients
      with primary breast carcinoma was analyzed by the Cox proportional hazards model.
      RESULTS: Thirteen of the 825 patients developed a subsequent endometrial
      carcinoma. The cumulative incidence of endometrial carcinoma was 1.58%. Four of
      13 patients who subsequently developed endometrial carcinoma received tamoxifen
      and 9 had not received tamoxifen. The relative risk of endometrial carcinoma by
      total dose of tamoxifen exposure was 1.0001 (P = 0.0145). There was no
      statistically significant correlation between the cumulative dose of tamoxifen or
      the length of tamoxifen treatment and the histologic type and grade of
      endometrial carcinoma. In addition, there was no statistical difference in the
      prognosis of endometrial carcinoma between the patients who received tamoxifen
      and patients who did not. CONCLUSIONS: The results of this study show that
      tamoxifen use does not appear to increase the incidence of subsequent endometrial
      carcinoma in patients with primary breast carcinoma who underwent annual
      screening for gynecologic carcinoma.

PMID- 9576292
TI  - Minimally invasive breast carcinoma staging using lymphatic mapping with
      radiolabeled dextran.
AB  - BACKGROUND: The sentinel lymph node is defined as the first lymph node to receive
      drainage from a primary tumor. Based on this concept, the authors set out to
      evaluate whether the status of the sentinel lymph node can accurately predict
      whether breast tumor cells have metastasized to the axillary lymphatic basin.
      METHODS: Radiolabeled dextran was injected into the site of the breast tumor. In
      the operating room, a portable gamma detector probe was used to identify the
      exact location of the sentinel lymph node(s). After identifying and excising the
      radioactive sentinel lymph node specimens, a routine axillary lymph node
      dissection was performed. All lymph nodes were then subjected to hematoxylin and
      eosin (H & E) staining, and the sentinel lymph nodes were subjected to additional
      cytokeratin immunohistochemistry. RESULTS: Of the 41 patients who participated in
      the study, 18 had tumor metastasis to their axillary lymph nodes. In all 18 of
      these cases, the sentinel lymph node(s) contained cancer detected by either H & E
      staining or cytokeratin immunohistochemistry. CONCLUSIONS: The status of the
      sentinel lymph node(s) appears to predict accurately whether breast tumor cells
      have metastasized to the axillary lymphatic basin. This new, minimally invasive
      technique for staging breast carcinoma should be further validated in a large,
      multi-institutional clinical trial.

PMID- 9576293
TI  - Immunohistochemical detection of sex steroid receptors, cyclins, and cyclin
      dependent kinases in the normal and neoplastic squamous epithelia of the uterine
      cervix.
AB  - BACKGROUND: Malignant transformation of sex steroid-dependent tissues has been
      reported to be associated with abnormal expression of sex steroid receptors. In
      addition, abnormalities of cell cycle-related molecules have been demonstrated in
      various malignancies. However, expression of steroid receptors and cell cycle
      related molecules in the process of malignant transformation of the ectocervical
      squamous epithelium, which also is a sex steroid-dependent tissue, has not been
      elucidated fully. METHODS: Immunohistochemical staining was performed on formalin
      fixed, paraffin embedded tissue sections of normal squamous epithelia (30 cases),
      cervical intraepithelial neoplasia (CIN) (21 cases), and invasive squamous
      carcinoma (SCC) (33 cases), using antibodies against estrogen receptors (ER),
      progesterone receptors (PR), cyclins (E, A, and B1), cyclin-dependent kinases
      (cdk2 and cdc2), and p53 protein. In addition, growth activity of SCC was
      evaluated by Ki-67 labeling. RESULTS: In the normal epithelia, diffuse
      proportionate to regional expression of ER/PR and sporadic expression of
      cyclins/cdks were observed mainly in the parabasal cells irrespective of the
      menstrual cycle. In the neoplastic lesions, the expression of ER markedly
      decreased; however, the expression of PR increased. The expression of cyclins,
      cdks, and p53 was increased in a considerable number of these neoplastic cases.
      In addition, cyclin A positive SCC had elevated Ki-67 labeling, whereas cyclin E
      positive SCC cases had lower Ki-67 labeling. CONCLUSIONS: These findings suggest
      that malignant transformation of ectocervical epithelia is associated with loss
      of normal growth control by steroid hormones as well as with the acquisition of
      abnormal cell cycle regulatory mechanisms.

PMID- 9576294
TI  - CA 125 may not reflect disease status in patients with uterine serous carcinoma.
AB  - BACKGROUND: Although CA 125 level correlates with response to therapy in patients
      with serous carcinoma of the ovary, the utility of CA 125 in patients with high
      risk or metastatic endometrial carcinoma has not been established. METHODS: CA
      125 was tested as a marker of disease status in patients with endometrial serous
      carcinoma (SC) undergoing adjuvant chemotherapy. All patients received monthly
      intravenous chemotherapy with cisplatin, cyclophosphamide, and doxorubicin at
      standard doses (median number of courses, 6; range, 2-8 courses). Serum CA 125
      was measured at diagnosis and before each course. After the completion of
      chemotherapy, patients were examined every 3 months and the CA 125 level was
      measured. RESULTS: A total of 220 serum specimens from 15 patients with invasive
      SC were analyzed. All five patients who died of disease had clinical or
      radiographic evidence of tumor, which CA 125 elevation did not precede or
      predict. One patient with advanced disease at staging never had an elevated CA
      125 level but died of disseminated disease 14 months after diagnosis. At last
      follow-up, 3 patients who were without evidence of disease > 36 months from
      diagnosis had significant false-positive elevations in their CA 125 level (>50
      u/mL) lasting 1, 2, and 4 months, respectively, during therapy. The sensitivity
      for advanced disease was only 57% at presentation. CONCLUSIONS: CA 125 may
      reflect advanced stage disease and portend a poor prognosis, but may not add
      information to that gained by history and physical examination, preoperative
      studies, or surgery that already is mandated by this high risk histology. This
      circulating marker appears to have limited utility in monitoring the effects of
      adjuvant therapy for SC, and may not predict recurrence in the absence of other
      clinical findings.

PMID- 9576295
TI  - 1H-magnetic resonance spectroscopy: a new technique to discriminate benign from
      malignant ovarian tumors.
AB  - BACKGROUND: Currently used techniques such as ultrasound, computed tomography,
      and magnetic resonance imaging are not fully capable of differentiating benign
      from malignant ovarian tumors. Magnetic resonance spectroscopy (MRS) may help
      solve this clinical problem by analyzing the composition of fluid from ovarian
      cysts. METHODS: The authors studied fluid samples from 28 different ovarian
      cysts. Nine patients were found to have a malignant ovarian tumor whereas 19
      patients had benign cysts. Single pulse 1H-Nuclear Magnetic Resonance spectra
      were obtained in all fluid samples. RESULTS: Compared with the group of benign
      epithelial cysts (n = 17) the 8 malignant epithelial ovarian cysts had
      significantly higher levels of lactate, isoleucine, valine, 3-hydroxybutyric
      acid, methionine, and alanine (P < 0.05). In two benign cysts (endometrioma and
      mature teratoma) surprisingly high levels were found for a large number of
      compounds. Values were as high as 100-fold the values in fluid from benign cysts.
      CONCLUSIONS: 1H-NMR spectroscopy demonstrates significant differences in
      metabolite concentration between benign and malignant ovarian cysts. This
      ultimately may lead to the noninvasive differential diagnosis of ovarian tumors
      by in vivo MRS.

PMID- 9576296
TI  - Primary ovarian sarcoma: analysis of prognostic variables and the role of
      surgical cytoreduction.
AB  - BACKGROUND: Data regarding the value of cytoreduction and cell histology in
      ovarian sarcomas are limited. The goal of this study was to assess the value of
      surgical cytoreduction, preoperative CA 125 levels, stage, histology, and
      platinum-based chemotherapy in the primary treatment of ovarian sarcomas.
      METHODS: A retrospective analysis of 47 women with primary ovarian sarcomas was
      performed. RESULTS: Forty-one patients (87%) presented with advanced stage
      disease (International Federation of Gynecology and Obstetrics Stage III or IV).
      Optimal surgical cytoreduction (< 1 cm residual tumor burden) was achieved in 25
      patients (53%). Forty patients (85%) had a malignant mixed mullerian tumor
      whereas 7 patients had a pure sarcoma. Eighteen women with mixed mullerian tumors
      had homologous tumors and 22 had heterologous elements. Patients treated with
      platinum-based chemotherapy were significantly more likely to have a response (P
      = 0.008) compared with those treated with other regimens. Treatment with platinum
      based chemotherapy also showed a survival advantage (P = 0.03). Preoperative CA
      125 levels were elevated (> 35 U/mL) in 93% of patients with ovarian sarcomas. A
      preoperative CA 125 level < 75 U/mL was significantly associated with better
      survival (P = 0.01). In univariate analysis, other significant predictors of
      improved survival were early stage (P = 0.04), homologous tumors (P < 0.05), and
      optimal surgical cytoreduction (P < 0.001). In multivariate analysis of various
      prognostic variables, optimal surgical cytoreduction (P < 0.001) was the most
      significant factor, followed by histologic subtype (P < 0.02). CONCLUSIONS:
      Ovarian sarcomas are rare malignancies with a poor prognosis. All women with
      suspected ovarian carcinoma or sarcoma should have a preoperative CA 125 level
      taken. Surgical cytoreduction to a residual tumor burden of < or = 1 cm improves
      outcome and should be the goal of surgery. Although the optimal consolidation
      chemotherapy regimen remains unknown, platinum should be included as part of the
      regimen.

PMID- 9576297
TI  - Image analysis combined with visual cytology in the early detection of recurrent
      bladder carcinoma.
AB  - BACKGROUND: Early detection of recurrent transitional cell carcinoma of the
      bladder (TCC) is important to permit early treatment, which produces maximal
      preservation of the bladder and maximum survival. METHODS: This retrospective
      cohort study attempted to determine the period of time over which urinary DNA
      image analysis combined with visual cytology is useful in the early detection of
      recurrent TCC of the bladder. The authors believe this study is unique in that it
      measured the effectiveness of this test (image analysis plus visual cytology
      combined) at varying times before clinical diagnosis of recurrence was made. The
      cohort was comprised of 175 urologic patients from urologic practices across the
      U.S. Data, collected between January 1991 and February 1994, included cystoscopy,
      biopsy, DNA image analysis, and visual cytologic reports. RESULTS: Sixty patients
      in the cohort were found to have active TCC whereas 115 patients had a history
      of, but no active, disease during the follow-up period. As expected, the
      sensitivity and specificity of DNA image analysis in combination with visual
      cytology, and DNA image analysis alone, were greatest when urinary samples were
      obtained close to the time of diagnosis. In general, the longer the interval from
      the combined tests to the time of diagnosis, the lower the sensitivity. The
      combined tests had predictive value up to 3 months prior to clinical diagnosis
      when any detectable cytologic abnormality was considered positive. At the optimal
      cutoff points as determined from receiver operating characteristic curves,
      sensitivity increased when DNA image analysis was supplemented with visual
      cytology. CONCLUSIONS: The combination of DNA image analysis and visual cytology
      provides a better method for the early detection of recurrent TCC than DNA image
      analysis alone. This test potentially may be useful in providing information
      regarding bladder tumor recurrence up to 3 months prior to clinical evidence of
      disease.

PMID- 9576298
TI  - The safety and efficacy of stereotactic biopsy for intracranial lesions.
AB  - BACKGROUND: Stereotactic brain biopsy is considered by many physicians to have
      significant morbidity and mortality rates with a high risk of sampling error
      resulting in misdiagnosis. The technical aspects necessary to perform the
      procedure safely and effectively are unfamiliar to most physicians. METHODS:
      After reporting his initial results with stereotactic brain biopsy, several
      modifications were implemented by the author to improve the morbidity, mortality,
      and diagnostic yield rates, including complex surgical planning with regard to
      patient selection, biopsy trajectory, imaging technique, target choice, and
      intraoperative pathologic review. The results of implementing these modifications
      were examined retrospectively in 134 consecutive brain biopsies. RESULTS: One
      hundred and thirty-four stereotactic brain biopsies were performed in 122
      patients. Computed tomography guidance was used in 85 patients (63%) and magnetic
      resonance imaging was used in 49 patients (37%). Sixty-four lesions (48%) were
      located in the right hemisphere, 61 (45%) in the left, and 9 (7%) in the midline.
      The most common diagnoses included 62 malignant brain tumors (46%), 24 benign
      brain tumors (18%), 23 neurologic disorders (17%), and 20 infections (15%). Five
      biopsies (4%) did not demonstrate a pathologic process for an overall diagnostic
      yield of 96%. Reasons for diagnostic failure included lesion location adjacent to
      the ventricular system, inaccurate targeting, and the inability to penetrate the
      tumor. One patient sustained a neurologic deficit after the biopsy for a
      morbidity rate of 0.7% and one sustained a fatal hemorrhage during the biopsy of
      a vascular tumor for a mortality rate of 0.7%. These results are comparable to
      those reported in 7471 biopsies (current series included) in which the morbidity
      rate was 3.5%, the mortality rate was 0.7%, and the diagnostic yield was 91%.
      CONCLUSIONS: Stereotactic brain biopsy is an extremely safe and effective
      procedure for evaluating intracranial lesions. Complex surgical planning can
      decrease the risk of potential complications and the use of intraoperative
      pathologic examination can improve the diagnostic yield for this procedure.

PMID- 9576299
TI  - Leptomeningeal metastases from solid tumors: a comparison of two prospective
      series treated with and without intra-cerebrospinal fluid chemotherapy.
AB  - BACKGROUND: It has been suggested that an aggressive treatment of patients with
      leptomeningeal metastases (LM) that groups radiotherapy and intra-cerebrospinal
      fluid (intra-CSF) chemotherapy has improved treatment outcomes. Based on their
      previous series of 137 patients treated with such an intensive standard protocol,
      the authors expected 20% of the patients to maintain their responses for at least
      6 months after withdrawal of therapy. They also observed that, in patients with
      solid tumors, a partial response was compatable with sustained off-therapy
      response and that the maximal response was reached soon after completion of
      radiotherapy. The authors concluded that the role of intra-CSF chemotherapy, with
      its associated high rate of complications, is unclear. In this study, which was a
      further evaluation of this dilemma, they compared the outcomes of two prospective
      treatment protocols that were identical in their use of radiotherapy and systemic
      chemotherapy and varied only in their inclusion or exclusion of intra-CSF
      chemotherapy. METHODS: Adult patients with LM from systemic solid tumors were
      prospectively included in the treatment protocol active at the time of their
      diagnosis. Group 1 comprised 54 patients treated by radiotherapy, intra-CSF
      chemotherapy, and systemic therapy, whereas Group 2 comprised 50 patients treated
      with radiotherapy, and systemic chemotherapy but no intra-CSF chemotherapy.
      RESULTS: The analysis of treatment outcomes was performed retrospectively. The
      median patient age and distribution of primary neoplasms did not differ between
      the two groups. The proportion of early deaths that occurred during radiotherapy
      was similar for the two groups, as was the overall rate of response to treatment.
      The two groups also had the same median survival, which was 4 months for both
      groups, as well as the same proportion of long term survivors. Thirty-one percent
      of patients in Group 1 developed early complications related to intra-CSF
      chemotherapy, whereas patients in Group 2 were spared these complications.
      Delayed symptomatic leukoencephalopathy was observed in 20% of Group 1 patients
      compared with none in Group 2 (P = 0.02). CONCLUSIONS: The exclusion of intra-CSF
      chemotherapy from the treatment schedule of patients with LM does not change
      their overall response to treatment, their median survival, or the proportion of
      long term survivors. It does, however, significantly reduce the rate of early and
      delayed treatment-related complications.

PMID- 9576300
TI  - Acquired Glanzmann's thrombasthenia associated with Hodgkin's lymphoma: a case
      report and review of the literature.
AB  - BACKGROUND: Acquired Glanzmann's thrombasthenia is a rare hemorrhagic diathesis
      resulting from impaired adhesive function of the platelet receptor GPIIb/IIIa
      (alpha(IIb)beta3). Typically, this disorder develops during adulthood, with
      patients manifesting fluctuating clinical and laboratory findings. To date, the
      underlying defect of most if not all cases of acquired Glanzmann's thrombasthenia
      results from an autoantibody or plasma protein inhibitor directed toward a
      demonstrably normal GPIIb/IIIa glycoprotein. METHODS: In this report, a patient
      with a history of treated Hodgkin's lymphoma presented with a severe hemorrhagic
      diathesis characterized by mild thrombocytopenia, a prolonged bleeding time, and
      defective platelet aggregation. RESULTS: Examination of the patient's platelet
      GPIIb/IIIa by Western blot analysis revealed no abnormality. Mixing studies
      demonstrated a non-immunoglobulin G plasma inhibitory factor, whereas flow
      cytometry analysis revealed elevated platelet-associated immunoglobulin (Ig) M.
      After an emergency colectomy for severe hemorrhage, the patient's qualitative and
      quantitative platelet parameters significantly improved. Pathology of the
      resected colonic segment demonstrated atypical lymphoid hyperplastic lesions.
      CONCLUSIONS: To the authors' knowledge, this is the first reported case of
      acquired Glanzmann's thrombasthenia associated with a putative IgM autoantibody.
      Furthermore, this report verifies the association of acquired thrombasthenia with
      lymphoproliferative disease. Although rare, awareness of this hemorrhagic
      diathesis as a possible sequelae of active or treated lymphoid disorders should
      encourage clinical vigilance of these patients.

PMID- 9576301
TI  - Trends in the survival of American Indian, Hispanic, and Non-Hispanic white
      cancer patients in New Mexico and Arizona, 1969-1994.
AB  - BACKGROUND: The burden of cancer mortality falls disproportionately on cancer
      patients belonging to ethnic minority groups. In the U.S., African American,
      Hispanic, and American Indian cancer patients are diagnosed at a more advanced
      stage and receive less appropriate treatment, resulting in poorer outcomes and
      higher mortality, than white cancer patients. The authors hypothesized that
      cancer control strategies based on earlier detection and more effective treatment
      may be most effective in increasing survival in groups with more advanced disease
      at diagnosis, less appropriate treatment, and lower survival. METHODS: Data
      collected by the New Mexico Tumor Registry, a member organization of the
      Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer
      Institute, afforded the authors an opportunity to investigate this hypothesis by
      studying trends in cancer survival for American Indians, Hispanics, and non
      Hispanic whites. The authors examined temporal trends and ethnic disparities in
      survival for in situ and invasive incident cancer cases at 25 sites diagnosed
      from 1969 through 1994 in New Mexico residents and in American Indians residing
      in Arizona. RESULTS: The distribution of stage became more favorable and the
      percentage of patients receiving appropriate treatment increased for all three
      ethnic groups during the study period. Survival improved for patients with cancer
      at most sites in each ethnic group; however, because the increase in survival was
      greater for non-Hispanic whites than for American Indians or Hispanics, the
      number of sites associated with disparities in survival among non-Hispanic
      whites, American Indians, and Hispanics increased. Differences in the
      distribution of age, gender, stage at diagnosis, histologic grade, and treatment
      did not completely explain the improved survival or the ethnic disparities
      regarding survival. CONCLUSIONS: Increased cancer control efforts were associated
      with earlier diagnosis, more patients receiving appropriate therapy, and improved
      survival for non-Hispanic whites, American Indians, and Hispanics. However, the
      improvement was greatest for non-Hispanic whites, and disparities in survival
      results for the different ethnic groups widened over the period of study. Cancer
      control strategies need to address the specific social, cultural, and biologic
      prognostic factors that affect different ethnic groups if disparities in outcomes
      are to be reduced.

PMID- 9576302
TI  - Long term use of megestrol acetate by cancer survivors for the treatment of hot
      flashes.
AB  - BACKGROUND: Hot flashes are often a troublesome symptom in breast carcinoma
      survivors and men with prostate carcinoma who have undergone androgen deprivation
      therapy. A previous clinical study demonstrated that, on a short term basis, low
      dose megestrol acetate markedly reduced hot flashes and was well tolerated.
      Little information has been available regarding the long term use of low dose
      megestrol acetate for hot flashes. METHODS: Patients previously enrolled on a
      randomized placebo-controlled trial that evaluated the short term use of
      megestrol acetate for hot flashes were contacted and interviewed by telephone.
      RESULTS: A total of 132 persons were contacted. Nine percent of the patients
      discontinued megestrol acetate after resolution of their hot flashes. Forty-five
      percent of the patients contacted were continuing to utilize megestrol acetate
      approximately 3 years beyond the conclusion of the 1992 study. Three-quarters of
      these patients were utilizing < or =20 mg of megestrol acetate per day. Potential
      toxicities attributed to megestrol acetate included episodes of chills, appetite
      stimulation/weight gain, vaginal bleeding, and carpal tunnel syndrome symptoms.
      CONCLUSIONS: A substantial proportion of patients continue to use megestrol
      acetate for periods of up to 3 years or longer with continued control of hot
      flashes. This treatment appears to be relatively well tolerated.

PMID- 9576303
TI  - Development of unfavorable hepatoblastoma in children of very low birth weight:
      results of a surgical and pathologic review.
AB  - BACKGROUND: The incidence of hepatoblastoma in children of very low birth weight
      (< 1500 g) is increasing in Japan. The authors reviewed surgical and pathologic
      aspects of the tumor to clarify the characteristics of the patients. METHODS:
      Fifteen patients (9 boys and 6 girls) who were diagnosed between the ages of 6-77
      months (median, 16 months) were identified from the data in the Japan Children's
      Cancer Registry and the data base of medical journals. The patients' birth
      weights ranged from 560-1380 g (median, 826 g) and the gestational age ranged
      from 23-33 weeks (median, 25 weeks). The medical records of all patients were
      reviewed and the patient's stage of disease according to the classification of
      the Japanese Society of Pediatric Surgeons, treatment, and outcome were analyzed.
      RESULTS: Ten tumors (67%) were classified as Stage II or IIIA and 5 (33%) were
      classified as Stage IIIB or IV. There was a significant correlation between the
      gestational age and tumor stage (correlation coefficient - 0.6851; P = 0.0048).
      The gestational age of the 5 patients with Stage IIIB or IV tumors was 23-25
      weeks (median, 24 weeks), whereas it was 25-33 weeks (median, 27.5 weeks) for the
      10 patients with Stage II or IIIA tumors (P = 0.0036). Birth weight ranged from
      560-826 g (median, 734 g) in Stage IIIB and IV patients, which was significantly
      lower than that in Stage II and IIIA patients (range, 607-1380 g, median, 909 g;
      P = 0.0500). Complete tumor resection was achieved in 7 patients (47%). The
      actuarial 2-year survival of all patients was 0.42, and the 2-year survival of
      patients who underwent complete tumor resection was 0.69, which was significantly
      better than the 2-year survival of those who underwent incomplete resection
      (0.17; P = 0.0211). The 2-year survival of the patients with tumors of well
      differentiated histology was 0.60, which also was significantly better than the 2
      year survival of those with tumors of poorly differentiated histology (0.19; P =
      0.0453). CONCLUSIONS: These results indicate that children of very low birth
      weight (< 1500 g) are at high risk of developing advanced hepatoblastomas and
      that hepatoblastoma with unfavorable biologic behavior develops in children who
      are extremely premature at birth. These new findings suggest the presence of
      etiologic factors relevant to the patient's immaturity and the development of
      unfavorable hepatoblastoma.

PMID- 9576304
TI  - Multivariate analysis of occult lymph node metastasis as a prognostic indicator
      for patients with squamous cell carcinoma of the oral cavity.

PMID- 9576305
TI  - Ultra-late recurrence (15 years or longer) of cutaneous melanoma.

PMID- 9576306
TI  - Fatal pulmonary toxicity resulting from treatment with gemcitabine.

PMID- 9576307
TI  - A hinged flange radiation carrier for the scalp: a clinical report.

PMID- 9576308
TI  - Color stability of dental composites as a function of shade.
AB  - STATEMENT OF PROBLEM: The selection of shade of composites for restorative
      applications may have a significant effect on color degradation through
      environmental exposure. PURPOSE: This study characterized the color changes in
      composites as a function of shade through environmental effects such as
      ultraviolet light exposure. MATERIAL AND METHODS: Five shades of two composites
      were subjected to ultraviolet light exposure at 37 degrees C for 24 hours after
      initial storage for 24 hours in distilled water at 37 degrees C. The lightness
      and chromaticity values of color were measured both before and after ultraviolet
      light exposure with a Minolta Chromameter. The total color change as well as
      changes in the lightness and chromaticity values were measured in the CIE L*a*b*
      scale and analyzed to monitor color degradation, if any. RESULTS: Color
      degradation was a significant function of shade and occurred primarily as an
      increase in yellowness. Color changes increased with the lightness of the shade
      in both composite systems. CONCLUSION: The lighter shades of composites were
      likely to be subject to higher color degradation through environmental effects of
      ultraviolet light exposure.

PMID- 9576309
TI  - Microscopic and energy dipersive x-ray analysis of surface adaptation of dental
      cements to dental ceramic surfaces.
AB  - STATEMENT OF PROBLEM: Clinical failure rates reported for acid etched/resin
      bonded ceramic restorations are significantly lower than those reported for
      restorations luted with traditional cements. This improved clinical performance
      may be associated with greater adaptation of the resin cements to the ceramic
      surfaces. PURPOSE: The objective of this study was to determine whether the use
      of resin cements accompanied by acid etching results in improved adaptation when
      compared with the use of zinc phosphate or glass ionomer cements. RESULTS: The
      results of this experiment indicate that superior adaptation of cement to ceramic
      is produced by acid etching and luting with resin cement. In addition, the
      results lead to the hypothesis that the high clinical failure rates reported for
      zinc phosphate or glass ionomer luted restorations are due either to incomplete
      adaptation or to failure within the cement. CONCLUSION: The findings indicate
      that the use of resin cements accompanied by acid etching of the ceramic surface
      is the preferred technique for clinical placement of all-ceramic restorations.

PMID- 9576310
TI  - Phosphate and thiophosphate primers for bonding prosthodontic luting materials to
      titanium.
AB  - STATEMENT OF PROBLEM: When resin-bonded prostheses are constructed with titanium,
      they must be strongly bonded with luting materials for the prostheses to
      withstand the oral environment over the long term. However, limited information
      is available about the bond durability between luting materials and titanium.
      PURPOSE: This study determined whether a phosphate and two thiophosphate primers
      increase bond strength and durability between a commercially available pure
      titanium and four luting agents. MATERIAL AND METHODS: Three primers and four
      luting agents were divided into three groups according to the type of acidic
      monomers: carboxylic acid derivatives (4-META, 4-AET, and MAC10), a phosphoric
      acid derivative (MDP), and a thiophosphoric acid derivative (MEPS). Disk
      specimens were bonded with 16 combinations of 3 primers and 4 luting agents,
      including 4 controls. Shear bond strengths were determined after 1-day immersion
      in water and after thermocycling for 100,000 cycles. RESULTS: Bond strengths were
      influenced by thermocycling, primer, luting agent, and their combinations. After
      thermocycling, the groups that demonstrated the highest bond strengths were six
      combinations of two primers (Cesead Opaque Primer and Metal Primer II) and three
      luting agents (Imperva Dual, Panavia 21, and Super-Bond C&B).

PMID- 9576311
TI  - Study on the surface of resins that burn without residues in the lost-wax
      procedure.
AB  - STATEMENT OF PROBLEM: When compared with waxes and prefabricated components made
      of dental alloys, processing resins is difficult and often results in a less
      accurate fit. The exact linear dimension is hard to realize, as the materials
      required for a dental casting are adjusted to dental waxes, and usually there are
      no special processing instructions for these resins. PURPOSE: The surface
      structure of 16 residue-free burning resins was determined to find which could
      enlarge the range of application for waxes in the dental casting technique.
      MATERIAL AND METHODS: A total of 480 specimens (30 castings for each of 16
      resins) were marked with an individually cut pyramid, which left an impression in
      the resin. This was distinctly visible in the metal after casting in "the lost
      form." The surfaces of these 480 specimens were measured in three dimensions with
      a positioning aid "before casting in resin" and "after casting in metal" by the
      Perthometer micrometer. All specimens were treated identically by the lost-wax
      process by using the rotation symmetry of the muffle. The differences in the
      surface data before casting in resin and after casting in metal characterize the
      quality of the particular resin. RESULTS: Surface roughness differed between the
      16 resins in the range of micrometer. CONCLUSIONS: With the dental casting
      technique, it is recommended that some resins replace waxes or wax-resin
      compositions.

PMID- 9576312
TI  - Intraoral repair of fiber-reinforced composite fixed partial dentures.
AB  - STATEMENT OF THE PROBLEM: Fractured composite facings may result in replacement
      of a fixed partial denture unless a reliable intraoral repair method can be
      provided. PURPOSE: This in vitro study tested the quality of an intraoral repair
      method for fractured facings of fixed partial dentures made of a fiber-reinforced
      composite system. MATERIAL AND METHODS: Shear bond strengths of a light-curing
      composite to a fiber-reinforced composite material were determined after
      different mechanical surface treatments. Aluminum oxide air abrading provided the
      most reliable bond strength values and therefore was used as a pretreatment for
      the facing repair of three-unit posterior fixed partial dentures. Facing repair
      was performed with the tested light-curing hybrid composite. Facing fracture
      strengths of repaired and original fixed partial dentures were determined after
      thermocycling and mechanical loading. RESULTS: Median facing fracture strength of
      the original fixed partial dentures was 1450 N after a simulated clinical service
      of 5 years. Facing fracture strengths of the repaired fixed partial dentures were
      significantly lower compared with the control group after an additional simulated
      2-year interval. However, the median fracture force was still 1000 N.
      CONCLUSIONS: The facing repair of a fiber-reinforced fixed partial denture with a
      hybrid composite in combination with aluminum oxide air-abrading pretreatment and
      silanization provided sufficient fracture strength. Therefore the replacement of
      the complete restoration may be avoided.

PMID- 9576313
TI  - Dimensional stability of record bases fabricated from light-polymerized composite
      using two methods.
AB  - STATEMENT OF PROBLEM: Record bases fabricated from resin-based composite, which
      undergoes polymerization shrinkage during curing, can distort during curing to
      produce significant gaps along the posterior border. PURPOSE: This study
      evaluated the pattern of gap formation that occurs over the palatal area of a
      maxillary record base fabricated from light-cured composite (Triad), and
      determined whether changes in the fabrication method affects the size and pattern
      of gap formation. Effects of composite width and passage of time on gap formation
      were also analyzed. MATERIAL AND METHODS: Twenty record bases were fabricated
      with two methods: (1) according to the manufacturer's directions, the entire
      surface of the record base was exposed to the curing light; and (2) the palatal
      area of the record base was covered with foil to prevent light penetration, and
      the base was light cured in three stages with readaptation of the uncured
      composite between stages. Ten record bases from each group were tested 1 hour
      after fabrication; the remaining 10 from each group were tested 7 days after
      fabrication. Measurements of adaptation were made at three points representing
      the right and left ridge crests and midpalatal areas. The first measurement was
      taken at the posterior border and subsequent measurements were made at 5 mm
      increments after reduction of the posterior border of the cast and record base
      with a model trimmer. RESULTS: Dimensional changes were observed in both
      procedures. The largest discrepancy occurred at the posterior border of record
      bases fabricated using method 1. Mean gap formation at the posterior border in
      this group after 1 hour was 454, 729, and 334 microm and 483, 841, and 330 microm
      after 7 days at points A, B, and C, respectively. Record bases fabricated with
      procedure 2 demonstrated mean gap sizes at the posterior border after 1 hour of
      219, 421, and 208 microm and 267, 403, and 192 microm after 7 days at points A,
      B, and C, respectively. No significant influence of composite width on gap size
      was found. CONCLUSION: The average gap size due to stage curing (method 2) was
      never greater than the corresponding gap that arose from the use of the
      manufacturer's recommendations (method 1). Limiting the amount of surface area
      exposed to the curing light and readapting the uncured composite to the cast
      between curing episodes can significantly reduce the mean gap size occurring at
      the posterior border.

PMID- 9576314
TI  - Evaluating the effect of soft lining materials on the growth of yeast.
AB  - STATEMENT OF PROBLEM: Soft lining materials continue to have a place in clinical
      removable prosthodontics. However, there is an increased probability of yeast
      colonization on soft lining materials. PURPOSE: This study (1) assessed a method
      of evaluating the effect of long-term soft lining materials on the growth of
      yeast and (2) investigated the effect five soft lining materials had on the
      growth of three species of yeast. MATERIAL AND METHODS: Coe Supersoft, Novus, and
      three experimental soft lining materials were investigated together with Candida
      albicans, Candida tropicalis, and Issatchenkia orientalis (formerly Candida
      krusei) yeasts. Strips of soft lining material incubated on blood agar plates
      were examined for inhibition of the growth of yeast. Soft lining materials soaked
      in sterile trypticase soya broth or water were inoculated with yeast and
      incubated. The change in colony forming units per milliliter from the initial
      load of yeast at 3 days was measured. Statistical analysis was performed with an
      independent paired Student t test. RESULTS: Inhibition of yeast growth occurred
      for two soft lining materials. Despite the presence of sufficient viable
      organisms, differences between the initial load of yeast and the 3-day results
      were mostly small, both for the test and control groups, suggesting that the
      material does not support the growth of the tested yeast during this period.
      CONCLUSIONS: The often described increased prevalence of yeast associated with
      soft lining materials in the oral environment is likely related to readily
      available nutrients in the mouth and the difficulty in maintaining and cleaning
      these materials.

PMID- 9576315
TI  - A retrospective multicenter evaluation of single tooth implant experience at
      three centers in the United Kingdom.
AB  - STATEMENT OF PROBLEM: Implant treatment in the United Kingdom has been provided
      mainly in specialist, regional dental hospitals. However, increasingly, general
      dentists are providing implant-supported prostheses in a private office setting.
      PURPOSE: This study investigated the nature, timing, and frequency of
      complications associated with single tooth implant therapy in a dental hospital
      and two dental offices. METHODS: The dental records of 58 patients provided with
      76 implants during the period of 1989-95 were reviewed retrospectively. Fifty
      three single tooth crowns on implants were placed by general dentists and 23 by
      specialists in the dental hospital. RESULTS: Implant survival rate was 96%.
      Twenty-eight guided bone regeneration procedures were required, including 13
      unplanned ones. Prosthodontic complications included the need for recontouring of
      three crowns and the recementation of three crowns. Only two abutment screws
      required retightening. Peri-implant soft tissue inflammation occurred around six
      crowns and recession around two. CONCLUSION: The single tooth implant-supported
      crown appears to be an effective and durable restorative treatment with a
      relatively low prevalence of postoperative complications.

PMID- 9576316
TI  - Retrospective review of 1170 endosseous implants placed in partially edentulous
      jaws.
AB  - STATEMENT OF PROBLEM: Implant-supported restorations in the partially edentulous
      jaw have been performed at the Mayo Clinic for more than 10 years. Clinical
      performance of the implants and the prostheses should be reported to ensure
      effectiveness of this procedure. PURPOSE: This retrospective study described
      results for implant survival, implant fracture rate, prosthetic complications,
      and design changes that may impact these results. MATERIAL AND METHODS: A
      retrospective chart review was conducted of all registered implant patients in a
      large multispecialty medical center. Patients with a partially edentulous jaw who
      had received endosseous implants to support and retain dental prostheses were
      included in this review. Implant survival and fracture, prosthetic complications,
      and demographic data were recorded and analyzed through Kaplan-Meier methods.
      RESULTS: A total of 1170 implants were placed in four anatomic locations:
      anterior maxilla, posterior maxilla, anterior mandible, or posterior mandible.
      Location of implants was shown to have no effect on implant survival (p =
      0.7398), implant fracture rates (p = 0.2385), screw loosening (p = 0.8253), or
      screw fracture (p = 0.2737). Development of new restorative components has
      resulted in significantly better rates of implant survival without fracture (p =
      0.0054), screw function without loosening (p < 0.0001) and screw function without
      fracture (p = 0.0013). Implant survival seems to have been improved with the new
      components (p = 0.0513). CONCLUSIONS: Implant survival in this study was
      independent of anatomic location of implants. Virtually all clinical performance
      factors were improved by design changes in implant restorative components that
      were brought to market in early 1991.

PMID- 9576317
TI  - A comparison of the effect of different occlusal forms in mandibular implant
      overdentures.
AB  - STATEMENT OF PROBLEM: Posterior tooth form selection for implant overdentures is
      made according to personal preference and experience using the concepts of
      conventional complete denture prosthodontics. PURPOSE: This study (1) compared
      the masticatory efficiency of three occlusal forms, 0 degrees, 30 degrees, and
      lingual contact (lingualized occlusion), in subjects with mandibular implant
      overdentures, and (2) determined their effects on the implant supporting tissues.
      MATERIAL AND METHODS: Eight patients who had four root form implants in the
      mandibular symphysis area connected with a Hader bar were selected. Maxillary and
      mandibular dentures were constructed for each patient with interchangeable
      posterior segments and the three occlusal forms were tested. The masticatory
      efficiency for each posterior tooth form was assessed with objective food tests
      and a subjective patient preference questionnaire. Periodic evaluation of implant
      supporting tissues also was performed. RESULTS: Reliability analysis showed that
      all R1 coefficients were > or =0.80 (<0.001), indicating high subject consistency
      between multiple chewing efficiency trials. MANOVA analysis indicated a
      significant difference in chewing efficiency among the three occlusal forms (p <
      0.001). The 0 degree occlusal form was associated with a significantly higher
      number of chewing strokes compared with 30 degrees or lingualized occlusal forms.
      The different occlusal forms were not found to have a clinically detrimental
      effect on the peri-implant soft or hard tissues. CONCLUSION: Chewing efficiency
      tests and patient preference ratings showed that 30 degree teeth and lingual
      contact provided better chewing efficiency than 0 degree teeth. None of the
      tested occlusal forms showed any clinical or radiographic detrimental effect on
      the implant-supporting tissues.

PMID- 9576318
TI  - Evaluation of the effectiveness of a technique to prevent screw loosening.
AB  - STATEMENT OF PROBLEM: Abutment screw loosening of single and multiple fixed
      partial dentures attached to external hexagonal implants is commonly encountered.
      PURPOSE: A technique that has been reported to prevent abutment screw loosening
      was tested with cyclic loading to determine its effectiveness. MATERIAL AND
      METHODS: A sample using identical components and test protocol, with the abutment
      screw tightened to 20 Ncm, was used as control. RESULTS: On the basis of the data
      obtained, the recommended technique does not increase resistance to screw
      loosening. The control sample sustained a mean number of cycles to screw
      loosening of more than twice that of the technique evaluated.

PMID- 9576319
TI  - Occlusal adjustment and the incidence of demand for temporomandibular disorder
      treatment.
AB  - STATEMENT OF PROBLEM: Contrary to clinical opinion, the structural risk from
      dental occlusion in temporomandibular disorders has been questioned or considered
      to be insignificant in clinical practice. PURPOSE: This study tested the effect
      of elimination of occlusal interference through occlusal adjustment, on the
      incidence of temporomandibular disorders. MATERIAL AND METHODS: In a controlled
      clinical trial of 146 healthy children and adolescents, half of the subjects
      underwent occlusal adjustment aimed at elimination of the presumed structural
      risk, and the other half underwent mock adjustment. Adjustments were repeated
      every 6 months over a period of 4 years. The outcome variable was the incidence
      of temporomandibular disorders, operatively defined as request for treatment of
      symptoms characteristic of the disorders with presence of clinical signs
      demonstrated in the muscles of mastication and/or jaw joint. RESULTS: The
      cumulative incidence rate was 9/67 in the mock adjustment group and 1/60 in the
      real adjustment group, for a relative risk of 8.06. The difference between groups
      was statistically significant (p = 0.019). CONCLUSIONS: Elimination of the
      presumed structural risk from the dental occlusion appeared to significantly
      reduce the incidence of temporomandibular disorders in a select group of young
      subjects.

PMID- 9576320
TI  - The effect of musculoskeletal facial pain on registration of maxillomandibular
      relationships and treatment planning: a synthesis of the literature.
AB  - STATEMENT OF PROBLEM: A significant number of patients exist who are in need of
      prosthodontic rehabilitation and who at the same time report musculoskeletal pain
      in the facial area. PURPOSE: This article, which is based on an assessment of
      both the past and the most recent basic science and clinical literature,
      evaluates the effect of musculoskeletal facial pain on two static (physiologic
      rest position and centric relation) and two dynamic (protrusive border and
      lateral border movements) maxillomandibular relationships. MATERIAL AND METHODS:
      To find the relevant studies addressing the association between musculoskeletal
      facial pain and maxillomandibular relationships, a MEDLINE search was conducted,
      which was complemented by a hand search in selected journals. RESULTS AND
      CONCLUSIONS: Musculoskeletal facial pain seems to variably affect the
      aforementioned positions and movements. Hence, the validity of maxillomandibular
      registrations in patients with existing facial pain is questioned. In those
      patients with facial pain who simultaneously are in need of a prosthodontic
      rehabilitation, clinicians should be cautious with regard to the timing of the
      restorative procedures.

PMID- 9576321
TI  - Dimensional stability and detail reproduction of irreversible hydrocolloid and
      elastomeric impressions disinfected by immersion.
AB  - STATEMENT OF PROBLEM: Because irreversible hydrocolloid impressions imbibe blood
      and saliva, immersion rather than spray disinfection may be more effective.
      Polyether has been shown to be dimensionally sensitive to immersion disinfection.
      PURPOSE: The aim of this study was to determine whether irreversible hydrocolloid
      and polyether impressions could be disinfected by immersion without sacrificing
      accuracy and surface quality. MATERIAL AND METHODS: Impressions were made of a
      master mandibular arch containing a crown preparation. Changes between the master
      and working casts were assessed. Irreversible hydrocolloids (Jeltrate;
      Palgaflex), a polyether (Impregum F), and an addition silicone (President) were
      used. Disinfectants were an iodophor (Biocide), a glyoxal glutaraldehyde
      (Impresept de), and a phenol glutaraldehyde (Sporicidin). The control was without
      disinfection. Casts were formed in Type IV gypsum. The roughness of working dies
      was also recorded and an analysis of variance was used for statistical
      evaluation. Results. Casts from disinfected irreversible hydrocolloid and
      elastomeric impressions maintained accuracy for anteroposterior and cross arch
      dimensions where differences from the master was less than 0.1%. Buccolingual and
      mesiodistal dimensions of working dies (disinfected and control) were 6 to 8
      microm larger than the master for addition silicones and 11 to 16 pm for
      polyethers. The occlusogingival dimension of dies for control and disinfected
      polyether was 9 pm longer than the master compared with -3 microm for addition
      silicone. The range of mean surface roughness of working dies made from
      irreversible hydrocolloids was 1.4 to 1.7 microm and ranged from 0.5 to 0.7
      microm for elastomeric impressions. Conclusion. Immersion disinfection of
      Jeltrate material with iodophor and Palgaflex material with glyoxal
      glutaraldehyde produced casts and dies as accurate as the control. Control and
      disinfected elastomeric impression produced dies as clinically accurate and
      smooth as the master. Disinfection of irreversible hydrocolloid impressions with
      the glyoxal and phenol glutaraldehyde produced a surface smoother than controls.

PMID- 9576322
TI  - Use of microwave energy to disinfect a long-term soft lining material
      contaminated with Candida albicans or Staphylococcus aureus.
AB  - STATEMENT OF PROBLEM: Soft lining materials have been found to be more
      susceptible to microbial adhesion than acrylic resin base materials. Denture
      hygiene is essential to maintain the serviceability of the denture, and microwave
      energy has been suggested for denture disinfection. PURPOSE: The purpose of this
      study was to determine the effectiveness of microwave energy in the disinfection
      of a long-term soft lining material. MATERIAL AND METHODS: A long-term soft
      lining material was contaminated with known microorganisms and the reduction of
      organism counts after test disinfection regimes calculated. The disinfection
      regimes were microwaving for 5 minutes, leaving dry overnight, and soaking
      overnight in a dilute sodium hypochlorite solution. The test microorganisms were
      Candida albicans or Staphylococcus aureus. RESULTS: For both organisms, soaking
      in sodium hypochlorite reduced the number of viable adherent microorganisms
      recovered significantly more than exposure to microwave energy, which led to
      greater reduction than leaving the lining material dry overnight (p < 0.001,
      Wilcoxon nonparametric signed rank test). CONCLUSION: With reference to the
      tested microorganisms, disinfection of Molloplast-b soft lining material in
      dilute sodium hypochlorite solution proved to be more effective than exposure to
      microwave energy, which in turn was more effective than leaving the lining dry
      overnight.

PMID- 9576323
TI  - Meta-analysis of fixed partial denture survival: prostheses and abutments.
AB  - STATEMENT OF PROBLEM: Few estimates of the probability of various outcomes
      associated with replacement of missing teeth with fixed partial dentures have
      been reported. Existing longitudinal studies have reported widely disparate
      results for the survival of fixed partial dentures, but these studies have used
      different definitions of failure and varying periods of follow-up. PURPOSE: This
      study used meta-analysis to formulate annual probability estimates for three
      categories of fixed partial denture or abutment survival. METHODS: A systematic
      review of the English language literature since 1960 identified eight studies
      that met the preset inclusion criteria. Estimated annual survival proportions
      were back-calculated based on the Kaplan-Meier model and these proportions were
      combined through a fixed effects model meta-analysis. The probabilities and
      corresponding 95% confidence intervals at 5, 10, and 15 years for the three
      categories of survival are reported. RESULTS: For the aggregate population
      represented by the limited longitudinal studies available, this meta-analysis
      indicated that less than 15% of fixed partial dentures were removed or in need of
      replacement at 10 years; whereas, nearly one third were removed or in need of
      replacement at 15 years. Less than 5% of abutments were removed at 10 years.

PMID- 9576324
TI  - Effects of periodontal support and fixed splinting on load transfer by removable
      partial dentures.
AB  - STATEMENT OF PROBLEM: Periodontally compromised abutment teeth complicate the
      design of bilateral distal extension removable partial dentures. PURPOSE: This
      study investigated the stress induced in the remaining oral structures by a
      bilateral distal extension I-bar-retained RPD with periodontally involved
      abutments in a photoelastic simulation model. MATERIAL AND METHODS: Composite
      photoelastic models were used as a simulation model in determining the stress
      generating characteristics of I-bar RPDs with varying degrees of periodontal
      involvement of the distal abutments. Effects of fixed splinting were considered.
      RESULTS AND CONCLUSIONS: Under the same load conditions, the highest stresses
      developed in the model with the largest osseous defect. Increasing the number of
      splinted teeth did not provide a proportional decrease in maximum stress levels.
      The more severe the osseous defect, the greater assistance was provided by
      splinting to periodontally sound teeth. This simulation study suggests that
      routine cross-arch splinting may not be appropriate.

PMID- 9576325
TI  - Retentive strengths of cast gold crowns using glass ionomer, compomer, or resin
      cement.
AB  - PURPOSE: The retention forces of a newly developed compomer cement (Dyract Cem),
      a glass ionomer cement (Ketac Cem Aplicap), and a resin cement (F21) were
      examined. MATERIAL AND METHODS: Cemented cast gold crowns were removed along the
      path of insertion with a Zwick universal testing device. The impact of both a
      cured and a noncured additional bonding layer that were applied to the inner
      surface of the crowns was examined across the Dyract Cem group. RESULTS: The mean
      adhesive strength was measured at 2.36 +/- 0.69 N/mm2 in the Ketac Cem group, at
      0.60 +/- 0.28 N/mm2 in the F21 group, and at 1.85 +/- 0.94 N/mm2 in the Dyract
      Cem group, respectively. The application of an additional bonding layer to the
      inner surface of the crowns did not significantly improve the retentive strength
      of Dyract Cem; the respective mean strengths were observed at 1.46 +/-0.33 N/mm2
      for the uncured and at 1.70 +/- 0.76 N/mm2 for the cured bonding layers.
      CONCLUSIONS: Dyract Cem and Ketac Cem showed significantly higher retentive
      strengths than F21 (p < 0.001, Wilcoxon test, 5% level). No significant
      difference was found in bond strength between Ketac Cem and Dyract Cem.

PMID- 9576326
TI  - Mechanical properties of laser-welded cast titanium joints under different
      conditions.
AB  - STATEMENT OF THE PROBLEM: Data on optimal conditions for laser welding commercial
      pure cast titanium used in dental restorations are sparse and not well
      established. PURPOSE: The mechanical properties of laser-welded cast commercially
      pure titanium under different laser welding conditions were evaluated to find the
      optimal parameters in terms of duration and voltage (energy level). MATERIAL AND
      METHODS: Fifty-seven cast pure titanium specimens according to ISO specification
      6871 were divided into nine experimental groups and one control group. The
      sectioned titanium bars were laser-welded under different duration (8, 10, and 12
      ms) and energy (290, 300, and 310 V) levels and evaluated for ranges of ultimate
      tensile strength (374 to 562 MPa), 0.2% yield strength (206 to 338 MPa), and
      percentage elongation (2.49% to 10.58%). RESULTS: Under a suitable laser-welding
      setting parameter the ultimate tensile strength and 0.2% yield strength of
      experimental groups were weaker than the unsectioned control specimens (control
      group ultimate tensile strength 540 +/- 11 MPa, 0.2% yield strength 258 +/- 49
      MPa) or too brittle (control group percentage elongation 12.41% +/- 1.83%). Two
      way ANOVA, nonparametric tests showed that voltage was the only significant
      factor for all parameters studied (p < 0.01). Optimal conditions were determined
      with three-dimensional response curves (305 V, 12 ms ultimate tensile strength;
      310 V, 10 ms 0.2% yield strength; 300 V, 12 ms percentage elongation).
      CONCLUSION: Optimal duration and voltage (energy level) used in laser welding for
      cast CP grade I titanium bar was superior to or comparable with and produced
      properties that were superior to or comparable with the unsectioned control
      specimens.

PMID- 9576327
TI  - Processed acrylic resin provisional restoration with lingual cast metal
      framework.
AB  - Fixed provisional prostheses are fabricated to maintain, improve, and/or change
      oral function and esthetics for varying periods. It is important to know when to
      provide a provisional prostheses and how to make one so that it will meet the
      needs of the patient. This article describes a modification of the design of a
      cast metal reinforced processed acrylic resin provisional restoration for
      extensive, long-term reconstruction with implants, because some of the treatments
      rendered to patients require temporization for up to 2 years. This design has
      been used by the authors since 1991, and has resulted in fewer problems of
      fracture of the provisional restorations. In addition, removable partial dentures
      are rarely needed, even when large spans exist between remaining abutments in
      serial extractions. This procedure also permits performing guided bone
      regeneration for deficient ridges without the problem of transmucosal loading,
      while still maintaining the patient's esthetics and function after surgery.

PMID- 9576328
TI  - Recombinant hemoglobin variants.

PMID- 9576329
TI  - Access to a syllabus of human hemoglobin variants (1996) via the World Wide Web.
AB  - Information on mutations in human hemoglobin is important in many efforts,
      including understanding the pathophysiology of hemoglobin diseases, developing
      therapies, elucidating the dynamics of sequence alterations inhuman populations,
      and dissecting the details of protein structure/function relationships.
      Currently, information is available on a large number of mutations and variants,
      but is distributed among thousands of papers. In an effort to organize this
      voluminous data set, two Syllabi have been prepared compiling succinct
      information on human hemoglobin abnormalities. In both of these, each entry
      provides amino acid and/or DNA sequence alterations, hematological and clinical
      data, methodology used for characterization, ethnic distribution, and functional
      properties and stability of the hemoglobin, together with appropriate literature
      references. A Syllabus of Human Hemoglobin Variants (1996) describes 693 abnormal
      hemoglobins resulting from alterations in the alpha-, beta-, gamma-, and delta
      globin chains, including special abnormalities such as double mutations, hybrid
      chains, elongated chains, deletions, and insertions. We have converted this
      resource to an electronic form that is accessible via the World Wide Web at the
      Globin Gene Server (http://globin.cse.psu.edu). Hyperlinks are provided from each
      entry in the tables of variants to the corresponding full description. In
      addition, a simple query interface allows the user to find all entries containing
      a designated word or phrase. We are in the process of converting A Syllabus of
      Thalassemia Mutations (1997) to a similar electronic format.

PMID- 9576330
TI  - HB Les Andelys [alpha83(F4)LEU-->PRO]: a new moderately unstable variant.
AB  - Hb Les Andelys [alpha83(F4)Leu-->Pro] is a mildly unstable variant that was found
      during glycated hemoglobin measurement in a French family. In this hemoglobin
      molecule the affected site, in the alpha chain, and the amino acid substitution
      are identical to those of Hb Santa Ana, an unstable beta chain variant. The
      structural abnormality was demonstrated by protein chemistry methods, involving,
      in addition to the classical techniques, a selective precipitation of the
      abnormal hemoglobin by isopropanol and a mass spectrometry analysis of the alphaT
      9 peptide following carboxypeptidase digestion. DNA sequencing demonstrated that
      the mutation was CTG-->CCG at codon 83 of the alpha2 gene.

PMID- 9576332
TI  - HB S-HB Monroe; a sickle cell-beta-thalassemia syndrome.

PMID- 9576331
TI  - Molecular basis of beta-thalassemia in the Maldives.
AB  - We have systematically analyzed beta-thalassemia genes using polymerase chain
      reaction-related techniques, dot-blot hybridization with oligonucleotide probes,
      allele specific-polymerase chain reaction, and sequencing of amplified DNA
      fragments from 41 unrelated patients, including 37 beta-thalassemia homozygotes,
      three with beta-thalassemia/Hb E, and one with beta-thalassemia/Hb S. Four
      different beta-thalassemia mutations were detected in 78 alleles. These are the
      IVS-I-5 (G-->C), codon 30 (AGG-->ACG) [also indicated as IVS-I (-1)], IVS-I-1 (G-
      >A), and codons 41/42 (-TTCT) mutations. The distribution of the beta-thalassemia
      mutations in the Maldives is 58 alleles (74.3%) with the IVS-I-5 (G-->C)
      mutation, 12 (15.4%) with the codon 30 (AGG-->ACG) mutation, seven (9%) with the
      IVS-I-1 (G-->A) mutation, and one with the codons 41/42 (-TTCT) mutation. The
      first three mutations account for 98.7% of the total number of beta-thalassemia
      chromosomes studied. These mutations are clustered in the region spanning 6 bp
      around the junction of exon 1 and the first intervening sequence of the beta
      globin gene. These observations have significant implications for setting up a
      thalassemia prevention and control program in the Maldives. Analysis of
      haplotypes and frameworks of chromosomes bearing each beta-thalassemia mutation
      suggested that the origin and spread of these mutations were reflected by the
      historical record.

PMID- 9576333
TI  - HB H disease with homozygosity for red cell G6PD deficiency in a Turkish female.

PMID- 9576334
TI  - HB Taybe: description of genetics and laboratory findings in an Israeli Arab
      family.

PMID- 9576336
TI  - The beta- and delta-thalassemia repository (Ninth Edition; Part I).

PMID- 9576335
TI  - A further note on the combination of an alpha chain variant with beta
      thalassemia.

PMID- 9576337
TI  - Detection of bovine viral diarrhea virus in the ovaries of cattle acutely
      infected with bovine viral diarrhea virus.
AB  - Bovine viral diarrhea virus (BVDV) is recognized worldwide as a major cause of
      economic loss in cattle. Infection with BVDV can result in several clinical
      outcomes. However, the reproductive consequences may be the most important.
      Infertility, early embryonic death, abortion, and congenital anomalies have all
      been reported following acute infection with BVDV. The cause of infertility
      following acute BVDV infection is not known. BVDV has been isolated from the
      bovine ovary and has been associated with chronic oophoritis. The purpose of this
      study was to identify the ovarian cell types infected with BVDV following acute
      infection. Twelve heifers were acutely infected with noncytopathic BVDV, and
      ovariectomies were performed between 4 and 60 days postinfection. BVDV was
      isolated on days 6 and 8 postinfection. Viral antigen was detected in macrophage
      like cells and stromal cells in the ovarian cortex and oophoritis was evident
      from 6 to 60 days postinfection. These findings indicate that acute infection
      with BVDV may result in changes in ovarian function that could lead to reduced
      fertility.

PMID- 9576338
TI  - Detection of cytopathic bovine viral diarrhea virus in the ovaries of cattle
      following immunization with a modified live bovine viral diarrhea virus vaccine.
AB  - Economic loss from infection with bovine viral diarrhea virus (BVDV) is of
      worldwide concern. The unique pathogenesis and antigenic variability of BVDV have
      made this virus challenging to control. Vaccination programs are a major
      component of control and prevention strategies. Both killed and modified live
      vaccines are commercially available. Choice between killed and modified live
      vaccines is controversial. Of major concern is the safety of modified live
      vaccines. Little information is available on their tissue tropism and potential
      for causing pathology, especially with respect to the reproductive system. The
      objective of this study was to determine if BVDV could be detected in the ovary
      of cattle following immunization with a modified live BVDV vaccine. In 2 separate
      trials, 6 heifers and 4 mature cows were immunized with a modified live BVDV
      vaccine and ovaries were removed between 7 and 30 days postvaccination.
      Cytopathic BVDV was isolated from ovaries removed on days 8, 10, and 12. BVDV
      antigen was detected using immunohistochemistry on days 10-30. These findings are
      significant because replication of virus in the ovary could cause ovarian
      dysfunction, resulting in reduced fertility.

PMID- 9576339
TI  - Prevalence of bovine viral diarrhea virus genotypes and antibody against those
      viral genotypes in fetal bovine serum.
AB  - One thousand lots of pooled fetal bovine serum (FBS) were tested for
      contamination with bovine viral diarrhea virus (BVDV) and/or for contamination
      with neutralizing antibody against BVDV. Noncytopathic or cytopathic BVDV was
      isolated from 203 lots of FBS. Analysis of the viral isolates identified 115 type
      1 and 65 type 2 BVDV isolates. An additional 23 virus isolates were mixtures of >
      or = 2 BVDV isolates and were not classified to viral genotype. Further
      characterization of the type 1 viruses identified 51 subgenotype 1a and 64
      subgenotype 1b BVDV isolates. Viral neutralizing antibody was detected in 113
      lots of FBS. Differential viral neutralization indicated that type 1 BVDV induced
      the antibody detected in 48 lots of FBS and type 2 BVDV induced the antibody
      detected in 16 lots of FBS.

PMID- 9576340
TI  - Differentiation of a porcine reproductive and respiratory syndrome virus vaccine
      strain from North American field strains by restriction fragment length
      polymorphism analysis of ORF 5.
AB  - The suitability of restriction fragment length polymorphism (RFLP) analysis for
      differentiating a porcine reproductive and respiratory syndrome virus (PRRSV)
      vaccine strain from other North American field strains was investigated. Open
      reading frame 5 nucleotide sequence data of the vaccine virus, its parent strain
      VR-2332, and 22 other strains of PRRSV included in this study indicated that 3
      restriction enzyme gel patterns characterize the vaccine virus and the parent
      strain genotype. The combined 3 RFLP patterns differentiate the vaccine and
      parent virus from other PRRSV strains. This test will be a valuable tool in
      epidemiologic studies and will be useful in identifying individual strains in
      cases of multistrain PRRSV infections.

PMID- 9576341
TI  - Gastrointestinal pathogenicity of adenoviruses and reoviruses isolated from
      broiler chickens in Alabama.
AB  - Adenoviruses and reoviruses isolated from commercial broiler chickens were
      evaluated for gastrointestinal pathogenicity in specific-pathogen-free Leghorn
      chickens. The viruses were originally isolated from either the proventriculus or
      a gastrointestinal pool of tissues of broiler chickens with proventriculitis or
      enteritis. Isolates were cloned by terminal dilution. Day-old chickens were
      inoculated by oral and ocular routes with undiluted tissue culture fluids (titers
      of 10[2]-10[4] TCID50/ml) and then examined at necropsy on days 5, 10, and 15
      postinoculation. Chickens in all virus groups (but not the control group)
      developed wet, unformed fecal droppings that persisted for the duration of the
      study. Mild lesions occurred in reovirus-inoculated chickens and included
      hyperplasia of lymphocyte aggregates in various organs and mild gizzard erosions.
      Chickens inoculated with adenovirus isolates developed marked gizzard erosions
      and necrotizing pancreatitis as well as mild proventriculitis. Intranuclear viral
      inclusion bodies occurred in gizzard epithelium and pancreatic acinar cells at
      the sites of lesions. Lymphocytic atrophy occurred in the bursa of Fabricius.
      Respective viruses were reisolated from proventriculus and duodenum collected
      from chickens of each group; no viruses were isolated from controls. Under the
      conditions of this study, adenovirus isolates were more pathogenic than the
      reovirus isolates in the digestive system.

PMID- 9576342
TI  - Comparison of immunohistochemistry, electron microscopy, and direct fluorescent
      antibody test for the detection of bovine coronavirus.
AB  - Bovine coronavirus (BCV) is 1 of the major causes of calf diarrhea and has also
      been implicated in respiratory infections of young calves and winter dysentery of
      adult cattle. Currently, transmission electron microscopy (TEM), direct
      fluorescent antibody (DFA), and enzyme-linked immunosorbent assay (ELISA)
      techniques are considered standard methods for the diagnosis of BCV infection.
      However, these techniques are not useful if fresh tissues and intestinal contents
      are not available for examination. The detection of viral antigens in formalin
      fixed, paraffin-embedded tissues using immunohistochemistry (IHC) is a suitable
      alternative. In the present study, 166 tissue specimens were tested by IHC for
      the presence of BCV. These tissues were from animals whose feces were positive
      for rotavirus and/or coronavirus by TEM. Some of these samples were also tested
      by DFA. Thus, TEM, DFA, and IHC were compared for the detection of BCV. There was
      56% agreement among the 3 methods (overall kappa = 0.368). When IHC was compared
      with TEM, 78% agreement was observed (kappa = 0.475). Similarly, IHC and DFA had
      64% agreement (kappa = 0.277). These kappa values indicate a moderate degree of
      agreement between IHC and TEM; agreement between IHC and DFA was fair. The
      results of this study indicate that IHC may be a suitable adjunct for the
      detection of BCV because of its simplicity, ease of use, and relatively close
      correlation with TEM results.

PMID- 9576343
TI  - Use of muscle fluid as a source of antibodies for serologic detection of
      Salmonella infection in slaughter pig herds.
AB  - Fluid drained from a muscle tissue sample was used as an alternative to serum for
      the detection of specific anti-Salmonella antibodies in an indirect LPS enzyme
      linked immunosorbent assay (ELISA). In the first study, serum and muscle fluid
      from 3 pigs experimentally infected with Salmonella typhimurium showed parallel
      dilution-response relationships when ELISA optical density (OD) values were
      plotted against sample dilution. ELISA results obtained with serum diluted 1:400
      corresponded to those from muscle fluid diluted 1:30. In a second study, using
      the predetermined dilutions of individually paired serum and muscle fluid samples
      from 103 pigs, a high degree of concordance between the serum ELISA and the
      muscle fluid ELISA was observed. Limits of agreement between the 2 methods were
      calculated as -8.9 to 12.3 OD%, which was considered acceptable. The muscle fluid
      ELISA had specificities of 0.91-1.0 and sensitivities of 0.80-0.89 at various
      cutoff values as compared with the serum ELISA. Muscle fluid is a useful
      postmortem alternative to serum when used with an ELISA to detect anti-Salmonella
      antibodies.

PMID- 9576344
TI  - Evaluation of a computerized antimicrobial susceptibility system with bacteria
      isolated from animals.
AB  - The BIOMIC is a computerized system used to calculate the minimal inhibitory
      concentration (MIC) of an antimicrobial agent from a zone of inhibition generated
      by a disk diffusion test. This system was developed using bacterial pathogens of
      human origin. This study investigated the use of the BIOMIC system for
      determining MICs for bacterial pathogens from animals. The MICs generated by the
      BIOMIC system were compared with the MICs generated using a broth microdilution
      testing method. A total of 663 drug-organism combinations was tested. These
      combinations included 3 species of gram-positive bacteria, 5 species of gram
      negative bacteria, and the antimicrobial agents ampicillin, gentamicin,
      cephalothin, ciprofloxacin, enrofloxacin, trimethoprim/sulfamethoxazole,
      tetracycline, and erythromycin. Overall, the MICs generated by the BIOMIC system
      correlated with the broth microdilution MICs for 72% of the total drug-organism
      combinations tested. The Pseudomonas aeruginosa strains tested showed the highest
      agreement between the 2 systems, with 100% for all antibacterial agents tested,
      whereas Pasteurella haemolytica, Pasteurella multocida, and enterococci showed
      the least agreement (76%, 57%, and 47%, respectively). Among these organisms,
      trimethoprim-sulfa showed the least agreement (31%) and ciprofloxacin showed the
      greatest (91%). These results indicate that the BIOMIC system could be a useful
      tool in veterinary medicine for producing quantitative antimicrobial
      susceptibility results. However, it is currently unreliable for some drug
      bacteria combinations. This discrepancy possibly could be corrected by
      modification of the software using data points generated by a large-scale study.

PMID- 9576345
TI  - Evaluation of techniques for the detection of toxigenic Pasteurella multocida
      strains from pigs.
AB  - Recently acquired field isolates and archived isolates from our collection of
      Pasteurella multocida were analyzed for production of dermonecrotic toxin.
      Detection of the toxin was carried out using a fetal lung feline (FLF) cell line
      and a commercial enzyme-linked immunosorbent assay (ELISA) kit. The dermonecrotic
      toxin gene (ToxA) was also detected using a polymerase chain reaction (PCR)
      technique. Results from the 3 methods were compared. Field isolates (group 1)
      came from a commercial herd that had clinical signs of atrophic rhinitis. Fifty
      six (17.9%) strains were isolated from 312 nasal swabs. Thirty-five of these
      strains belonged to serotype A and the rest (21/56), although probably serotype
      D, were not characterized further. All of these strains were toxin negative based
      on both the ELISA and FLF cell culture results. Five isolates gave faint bands in
      the PCR reaction, and the rest (51/56) were PCR negative. PCR and ELISA were also
      performed from the initial swab cultures (mixed cultures); 7 samples gave faint
      PCR bands, but ELISA results were all negative. Archived strains (group 2) had
      been isolated from clinical cases of atrophic rhinitis and from cases of
      pulmonary pasteurellosis. A total of 76 strains were analyzed; 46 were serotype
      A, and the rest (30) were serotype D. ELISA and FLF cell culture tests were
      negative for all serotype A strains; however, 3 strains showed faint bands in the
      PCR reaction. Fourteen serotype D strains showed positive results in both the
      ELISA and the FLF cell culture tests. PCR from these samples also gave positive
      results showing a strong band in the gel. However, 4 strains that were ELISA and
      FLF cell culture negative showed a faint band in the PCR reaction. The 3 methods
      gave similar results in the detection of the P. multocida dermonecrotic toxin.
      However, complete agreement among the tests was achieved only when strong PCR
      bands were considered positive. This is the first report that demonstrates the
      use of FLF cell line for the detection of toxigenic P. multocida.

PMID- 9576346
TI  - Normal reference intervals and the effects of time and feeding on serum bile acid
      concentrations in llamas.
AB  - Fifty clinically healthy llamas, 0.5-13 years of age (22 intact males, 10
      neutered males, 18 females), with no biochemical evidence of liver disease or
      hematologic abnormalities, were selected to establish serum bile acid reference
      intervals. Serum samples submitted to the clinical pathology laboratory were
      analyzed using a colorimetric enzymatic assay to establish bile acid reference
      intervals. A nonparametric distribution of llama bile acid concentrations was 1
      23 micromol/liter for llamas >1 year of age and 10-44 micromol/liter for llamas <
      or = 1 year of age. A significant difference was found between these 2 age
      groups. No correlation was detected between gender and bile acid concentrations.
      The reference intervals were 1.1-22.9 micromol/liter for llamas >1 year of age
      and 1.8-49.8 micromol/liter for llamas < or = 1 year of age. Additionally, a
      separate group of 10 healthy adult llamas (5 males, 5 females, 5-11 years of age)
      without biochemical or hematologic abnormalities was selected to assess the
      effects of feeding and time intervals on serum bile acid concentrations. These 10
      llamas were provided fresh water and hay ad libitum, and serum samples were
      obtained via an indwelling jugular catheter hourly for 11 hours. Llamas were then
      kept from food overnight (12 hours), and subsequent samples were taken prior to
      feeding (fasting baseline time, 23 hours after trial initiation) and
      postprandially at 0.5, 1, 2, 4, and 8 hours. In feeding trials, there was no
      consistent interaction between bile acid concentrations and time, feeding, or 12
      hour fasting. Prior feeding or time of day did not result in serum bile acid
      concentrations outside the reference interval, but concentrations from individual
      llamas varied within this interval over time.

PMID- 9576347
TI  - Aural polyp associated with cryptosporidiosis in an iguana (Iguana iguana).

PMID- 9576348
TI  - Determination of genotypic frequency of caprine mucopolysaccharidosis IIID.

PMID- 9576349
TI  - Distribution of antibody titers to bovine viral diarrhea virus in infected,
      exposed, and uninfected beef cattle.

PMID- 9576350
TI  - Serotyping of Chlamydia psittaci isolates from ratites.

PMID- 9576351
TI  - Ribotyping of Salmonella poona in iguana-associated zoonotic salmonellosis.

PMID- 9576352
TI  - Wesselsbron disease virus associated with abortions in goats in Botswana.

PMID- 9576353
TI  - Atrial adipofibrosis in a dog.

PMID- 9576354
TI  - Concurrent rabies and canine distemper encephalitis in a raccoon (Procyon lotor).

PMID- 9576355
TI  - Viable Borrelia burgdorferi in the urine of two clinically normal horses.

PMID- 9576356
TI  - Concurrent trichinosis and oral squamous cell carcinoma in a cat.

PMID- 9576357
TI  - Phaeohyphomycotic ependymitis in a cat.

PMID- 9576358
TI  - Australian tea tree (Melaleuca alternifolia) oil poisoning in three purebred
      cats.

PMID- 9576359
TI  - Lasalocid toxicosis in neonatal calves.

PMID- 9576360
TI  - Enhanced immunohistochemical detection of infectious agents in formalin-fixed,
      paraffin-embedded tissues following heat-mediated antigen retrieval.

PMID- 9576361
TI  - Nature and disposition of intracavity and intramembranous phospholipid surface
      active material and its role in peritoneal dialysis.

PMID- 9576362
TI  - Quality process initiatives can help dialysis centers improve patient outcomes
      and reduce costs.

PMID- 9576363
TI  - Surfactant barrier lining peritoneal mesothelium: lubricant and release agent.
AB  - OBJECTIVE: Five studies are described to determine whether there is an outermost
      lining of surface-active phospholipid (SAPL) adsorbed to the peritoneum and to
      quantify its ability to act as a release (antistick) agent and boundary lubricant
      by standard tests. METHODS: Using a hydrophobic probe (phosphin E),
      epifluorescence microscopy was used to demonstrate an outermost lining of
      oligolamellar SAPL by spectral analysis of the emitted light, a finding
      consistent with the appreciable hydrophobicity demonstrated on canine peritoneal
      mesothelium and its virtual elimination by incubation with bile salt. Good
      release and excellent lubricating capabilities of human peritoneal SAPL have been
      quantified as the release factor and coefficient of friction, respectively, by
      standard tests from the physical sciences. RESULTS: A well-defined outermost
      layer was clearly visible on peritoneal mesothelium whose color spectrum was
      identical to that produced by pure phosphatidylcholine ultrasonicated into its
      oligolamellar state. Further evidence for a SAPL lining was demonstrated by a
      parietal contact angle of 43 degrees (47 degrees visceral) on this surface and
      its virtual elimination by incubation with dilute bile salt. Human SAPL from
      continuous ambulatory peritoneal dialysis (CAPD) effluent proved an effective
      release agent, reducing adhesion by 67%, and an excellent lubricant as quantified
      by a coefficient of friction of 0.091 under load (1.9 kg/cm2). CONCLUSIONS: The
      good release and excellent lubricating properties of SAPL adsorbed to mesothelial
      surfaces are highly desirable in reducing wear and exfoliation of epithelial
      cells. In spanning epithelial cells, the same lining might also serve to render
      tight junctions tight and reduce macromolecular escape while compatible with many
      aspects of CAPD, including lipid permeability and conflicting results obtained
      from administering exogenous SAPL.

PMID- 9576364
TI  - Increase of intra-abdominal fat in patients treated with continuous ambulatory
      peritoneal dialysis.
AB  - OBJECTIVE: To evaluate changes in amount and distribution of body fat in patients
      treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN:
      Prospective study. Computed tomography (CT) and dual energy x-ray absorptiometry
      (DEXA) were used for determination of body composition at commencement of CAPD,
      and after a mean of 7.2 months of dialysis treatment. SETTING: CAPD unit at an
      academic teaching hospital. PATIENTS: The study included 19 consecutive patients
      who started CAPD during a 15-month time frame. Of these 19 patients, 12 (8 males)
      with a mean initial age of 60 years completed the study. MAIN OUTCOME MEASURES:
      Siemens Somatom HiQ (Erlangen, Germany) was used for CT of the abdomen and of the
      right thigh. Fat and muscle areas were expressed as square centimeters. The
      proportion of total fat mass was determined by body composition analysis using
      DEXA (DPX-L densitometer) (Lunar, Madison, WI, U.S.A.) and expressed as
      percentage of total body weight (FA%). RESULTS: Body weight changed from 67.1 to
      68.4 kg (p = 0.20), and the intra-abdominal fat area increased 22.8% (p = 0.02).
      This increase was predominantly seen in male patients (p = 0.007). The FAT%
      changed from 27.8% to 30.9% (p = 0.25), without difference between sexes.
      CONCLUSION: The increase of intra-abdominal fat found in this study may suggest a
      mechanism by which the established risk for CAPD patients to develop
      cardiovascular morbidity and mortality may be at least partially explained.

PMID- 9576365
TI  - Inflammatory demyelinating neuropathy in patients with end-stage renal disease
      receiving continuous ambulatory peritoneal dialysis (CAPD)
AB  - OBJECTIVE: To report on 3 patients with inflammatory demyelinating peripheral
      neuropathy in strong temporal coincidence with the initiation of peritoneal
      dialysis (PD) therapy. SETTING: Nephrology and Neurology Department of the
      University Hospital, Munich, Germany. PATIENTS: Three patients with end-stage
      renal failure presented with the clinical picture of inflammatory demyelinating
      peripheral neuropathy within 4 to 10 weeks after start of continuous ambulatory
      peritoneal dialysis (CAPD). They had acute or subacute onset of lower extremity
      or generalized weakness, diminished reflexes, elevated spinal fluid protein
      levels, and signs of demyelinating neuropathy on electrophysiological testing.
      MEASURES: Clinical follow-up, nerve conduction studies, cerebral spinal fluid
      (CSF). RESULTS: All patients did not improve under intensified PD therapy but
      took profit from immunomodulatory therapy. One bed-bound patient improved after
      change to hemodialysis and showed complete remission after renal transplantation.
      CONCLUSION: Because of strong temporal coincidence, a causal relationship between
      CAPD and inflammatory demyelinating peripheral neuropathies can be suspected in
      these 3 patients.

PMID- 9576366
TI  - Intraperitoneal pulse calcitriol in the treatment of secondary
      hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To determine whether it is practicable to use intraperitoneal
      calcitriol to treat continuous ambulatory peritoneal dialysis (CAPD) patients
      with secondary hyperparathyroidism and whether this form of therapy is effective
      and safe. DESIGN: A prospective, nonrandomized study. SETTING: Division of
      Nephrology, Tertiary Hospital. METHOD: Eight patients from our CAPD population
      were recruited (5 F, 3 M), aged 24 to 63 years (mean 38.9 +/- 7.6 yr). They had
      been on CAPD for 8 to 84 months (mean 47.6 +/- 24.6 months). All the patients had
      bone biopsy-proven secondary hyperparathyroidism with 2 patients showing mixed
      lesions. The CAPD system was changed to the twin-bag system (Ultrabag, Baxter
      Healthcare, McGaw Park, IL, U.S.A.) in all 8 patients, who were taught to inject
      the calcitriol directly through the short transfer set and the Tenckhoff catheter
      into the peritoneal cavity, twice per week before bedtime. Calcium carbonate or
      calcium acetate was used as the main phosphate binder. Intact parathyroid hormone
      level (iPTH), serum ionized calcium (iCa), serum phosphate, and serum total
      alkaline phosphatase (alk. phos.) levels were measured at baseline and then every
      4 weeks. The mean duration of follow-up was 10.5 months +/- 1.9 months. RESULTS:
      There was a significant drop of iPTH level from the pretreatment level of 100.6
      +/- 35.8 pmol/L to a level of 63.8 +/- 48.7 pmol/L at 24 weeks (p = 0.036). The
      lowest level of iPTH attained was 43.4 +/- 27.0 pmol/L at 48 weeks. Serum total
      alk. phos. also dropped from 232.4 +/- 83.3 IU/L pretreatment to 147.9 +/- 52.0
      IU/L at 24 weeks (p = 0.017). The decrease in alk. phos. level paralleled the
      decrease in iPTH level. The mean serum iCa level did not show any significant
      rise throughout the study period. The maximum dose of calcitriol used was 6.6 +/-
      1.5 microg/week and the average dose of calcitriol was 5.4 +/- 1.2 microg/week.
      One patient did not respond satisfactorily and she subsequently had a
      parathyroidectomy. Two episodes of peritonitis occurred during the study period,
      giving a peritonitis rate of one episode per 42 patient-months. There was no
      significant change in the urea clearance tests or the peritoneal equilibration
      tests before and after the study. CONCLUSION: Intraperitoneal calcitriol is
      practicable, effective, and safe in the treatment of secondary
      hyperparathyroidism in CAPD patients.

PMID- 9576367
TI  - Swan neck presternal peritoneal dialysis catheter: five-year experience in
      children.
AB  - OBJECTIVES: To reduce the incidence of exit-site infection (ESI) a new peritoneal
      dialysis (PD) catheter, the Swan neck presternal catheter (SNPC), composed of
      abdominal and presternal parts joined by a titanium connector, with the exit site
      located on the chest wall, was designed. DESIGN: A prospective study was
      undertaken to estimate the usefulness of the SNPC for continuous ambulatory
      peritoneal dialysis (CAPD) in children. SETTING: University Children's Hospital,
      Medical Academy, Warsaw, Poland. PATIENTS: From December 1991 to June 1997, 11
      SNPCs were implanted in 10 children for the following reasons: recurrent ESI in
      3, the presence of ureterocutaneostomies in 3, obesity in 3, the use of diapers
      in 2, young age in 1, and fecal incontinence in 1. More than one indication was
      present in some patients. In 7 patients the SNPC was the first PD catheter
      inserted. INTERVENTION: In all children the presternal catheter was implanted
      surgically by the modification of the technique described by Twardowski et al.
      RESULTS: The observation period ranged from 1-60 months. The rate of ESI was
      1/162 patient-months. The major complication was trauma of the exit site (4 times
      in 3 of 10 patients). In spite of leaving an extra length of the catheter in the
      entire subcutaneous tunnel at the time of implantation, the two parts of the SNPC
      became disconnected in 2 children (after 7 and 33 months respectively).
      CONCLUSION: Our results achieved with the SNPC in children are very good. The
      presternal catheter reduces the risk of ESI. However, the chest localization of
      the exit site does not help to prevent trauma in children. This type of PD
      catheter should be reserved for patients with specific indications.

PMID- 9576368
TI  - The effect of a nitric oxide inhibitor (L-NAME) on peritoneal transport during
      dialysis in rats.
AB  - OBJECTIVE: To assess the effect of an inhibitor of nitric oxide synthesis [N(G)
      nitro-L-arginine methyl ester (L-NAME)] on peritoneal transport during peritoneal
      dialysis (PD) and peritonitis in rats. METHODS: The authors studied peritoneal
      transport of small and large solutes, and net ultrafiltration (UF) in rats during
      PD with Dianeal 3.86 (Baxter, McGaw Park, IL, U.S.A.). They evaluated the effect
      of L-NAME used as an additive to dialysis fluid in concentrations 0.5-5 mg/mL on
      peritoneal transport of small and large molecules and on transperitoneal UF. In
      addition, they studied the effect of L-NAME (5 mg/mL) during acute peritonitis
      induced by lipopolysaccharides (5 microg/mL) given intraperitoneally. RESULTS:
      The addition of L-NAME to dialysis fluid increased the selectivity of the
      peritoneum and net UF during dialysis. Lipopolysaccharides used as an additive to
      the dialysis fluid, together with L-NAME, did not induce changes in
      transperitoneal transport of small and large solutes and did not cause a
      significant decline in net UF. L-NAME given intraperitoneally reduced both local
      and systemic production of nitric oxide, which might explain its effects on
      peritoneal transport. CONCLUSIONS: Nitric oxide is an important mediator of
      changes in peritoneal transport and its effect is especially significant during
      peritonitis.

PMID- 9576369
TI  - Peritoneal fluid and solute transport with different polyglucose formulations.
AB  - OBJECTIVE: To study peritoneal fluid and solute transport characteristics using
      different polyglucose solutions with and without the addition of glucose. DESIGN:
      Thirty-one rats were divided into three groups. A 4-hour dwell study with
      frequent dialysate and blood samples was performed in each rat using 25 mL of
      7.5% polyglucose solution (PG, n = 11), 7.5% polyglucose + 0.35% glucose solution
      (PG1, n = 12), or 3.75% polyglucose + 1.93% glucose solution (PG2, n = 8).
      Radiolabeled human albumin (RISA) was added to the solutions as an
      intraperitoneal volume (i.p.V) marker. In addition, polyglucose degradation was
      evaluated ex vivo over 24 hours. EXPERIMENTAL ANIMALS: Thirty-one male Sprague
      Dawley rats (300 g) were used. MAIN OUTCOME MEASURES: Fluid and solute (glucose,
      urea, sodium, potassium, and total protein) transport characteristics as well as
      changes in dialysate osmolality were evaluated. RESULTS: The i.p.V was higher in
      the PG1 and PG2 groups than in the PG group during the first 2 hours of the
      dwell. The i.p.V, in fact, decreased during the first hour of the dwell in the PG
      group. However, the net ultrafiltration at 4 hours tended to be lower in the PG2
      (3.2 +/- 1.5 mL) group compared to the PG (5.1 +/- 2.3 mL) and the PG1 groups
      (5.2 +/- 2.1 mL) (p = 0.07), and no significant difference was found between the
      PG and PG1 groups. Adding glucose to the PG solution increased the RISA
      elimination rate (KE, representing the fluid absorption rate from the peritoneal
      cavity): 25.5 +/- 8.2, 37.5 +/- 12.2, and 42.5 +/- 8.9 microL/min for the PG,
      PG1, and the PG2 group, respectively, p < 0.01. Dialysate osmolality (D[OS])
      increased with the dwell time in the PG and PG1 groups but decreased in the PG2
      group.The increase in D(OS) was partially due to the degradation of glucose
      polymer, which was supported by the marked increase in osmolality over 24 hours
      of incubation of PG solution with peritoneal fluid, ex vivo. The diffusive mass
      transport coefficient for the investigated solutes did not differ among the three
      groups (except for glucose, which was significantly lower in the PG group). The
      sieving coefficient for sodium was significantly higher in the PG group compared
      to the PG1 group (p < 0.05). CONCLUSION: Our results suggest that, although there
      was an initial decrease in the intraperitoneal dialysate volume, significant
      amounts of fluid can be removed by polyglucose solution during a single 4-hour
      dwell in rats, despite the low osmolality of the solution. The positive fluid
      removal induced by the PG solution is partially due to the lower fluid absorption
      rate associated with this solution and may, to some extent, also be due to the
      degradation of glucose polymer within the peritoneal cavity, resulting in
      increased dialysate osmolality. The addition of glucose to the polyglucose
      solution does not seem to improve ultrafiltration in a 4-hour dwell in the rat
      model. However, the peritoneal fluid absorption rate may be increased, and
      peritoneal transport of glucose and sodium may be altered, by adding glucose to
      the polyglucose solution.

PMID- 9576370
TI  - Pharmacokinetics of clodronate in peritoneal dialysis patients.
AB  - OBJECTIVE: To study the pharmacokinetics of clodronate in patients on continuous
      ambulatory peritoneal dialysis (CAPD). DESIGN: A single intravenous dose
      pharmacokinetic study. SETTING: University hospital. PATIENTS: Ten CAPD patients
      (3 female, 7 male, age 39-79 year, median 55). METHODS: Clodronate disodium in
      serum, urine, and dialysate was collected for 24 hours and analyzed by capillary
      gas chromatography with mass-selective detection. RESULTS: Only 7% of the infused
      dose of clodronate was eliminated through peritoneal dialysis during 24 hours.
      Clearance via CAPD (CL[CAPD]) was 2.4 +/- 0.6 mL/min, which was less than 10% of
      the total serum clearance (CL(tot), 26.0 +/- 19.3 mL/min). Even the kidneys were
      a more important route of elimination than CAPD in those patients with residual
      diuresis of more than 500 mL/24 hr. However, in all patients most of the
      clodronate serum clearance (77% +/- 13%) took place via routes other than
      peritoneal dialysis or kidneys, that is, via nonrenal-non-CAPD clearance
      (CL[NRD]). CL(NRD) most likely represents the part of the drug deposited in the
      skeleton. There was a positive correlation between CL(NRD) and the plasma intact
      parathyroid hormone concentration. CONCLUSIONS: CAPD removed clodronate poorly
      from the circulation. Most clearance took place via routes other than CAPD or
      kidneys. This CL(NRD) most likely represents the skeletal deposition of the drug,
      and this is related to the severity of hyperparathyroidism. When treating CAPD
      patients with hyperparathyroid bone disease, the administration of clodronate
      should be adjusted as in those subjects with severe renal failure.

PMID- 9576371
TI  - Replacement of amino acid and protein losses with 1.1% amino acid peritoneal
      dialysis solution.
AB  - OBJECTIVE: Losses of nutrients into dialysate may contribute to malnutrition.
      Peritoneal dialysis (PD) patients are reported to lose 3-4 g/day of amino acids
      (AAs) and 4-15 g/day of proteins. The extent to which one exchange with a 1.1% AA
      dialysis solution (Nutrineal, Baxter, Deerfield, IL, U.S.A.) offsets these losses
      was investigated in a 3-day inpatient study in 20 PD patients. DESIGN: Simple,
      open-label, cross-over study on consecutive days in a clinical research unit. On
      day 1 all patients were given a peritoneal equilibration test (PET). On day 2
      they received 1.5% dextrose Dianeal (Baxter) as the first exchange of the day and
      their usual regimen thereafter. On day 3, the first exchange of the day was the
      1.1% AA solution in place of 1.5% Dianeal and the usual PD regimen thereafter. On
      days 2 and 3 all dialysate effluent was collected and analyzed for AAs and
      proteins. Patients were maintained on a constant diet. RESULTS: Losses of AAs and
      total proteins on day 2 were 3.4 +/- 0.9 g and 5.8 +/- 2.4 g, respectively,
      totaling 9.2 +/- 2.7 g. The net uptake of AAs on day 3 was 17.6 +/- 2.6 g (80 +/-
      12% of the 22 g infused). Mean gains of AAs on day 3 exceeded losses of proteins
      and AAs on day 2, p < 0.001. Losses of total proteins, but not losses of AAs, and
      the net absorption of AAs from the dialysis solution were correlated directly
      with peritoneal membrane transport characteristics, obtained from the PET.
      CONCLUSION: Daily losses of AAs and proteins into dialysate are more than offset
      by gains of AAs absorbed from one exchange with 1.1% AA-based dialysis solution.
      Net gains of AAs exceeded losses of proteins and AAs in all patients studied. The
      difference was relatively constant across a wide range of membrane transport
      types. Net AA gains were approximately two times the total AA and protein losses.

PMID- 9576372
TI  - N-acetylglucosamine changes permeability of peritoneum during chronic peritoneal
      dialysis in rats.
AB  - OBJECTIVE: To evaluate the effect of supplementation of dialysis fluid with N
      acetylglucosamine (NAG) on the permeability of peritoneum during chronic
      peritoneal dialysis in rats. DESIGN: Experiments were performed on rats with
      surgically implanted peritoneal catheters. Dialysis solution [Dianeal 1.5%
      (Baxter, Deerfield, IL, U.S.A.) supplemented with either NAG 50 mmol/L or glucose
      50 mmol/L (control)] was infused intraperitoneally twice, every day, for 8 weeks.
      Peritoneal equilibration tests (PET) were performed in all animals at the
      beginning of the study and after 8 weeks of dialysis. Additionally, at the end of
      each week, dialysis solution infused in the morning was drained after 4 hours of
      intraperitoneal dwell. White blood cell count, creatinine, and total protein
      concentrations were measured in the effluent dialysate. After 8 weeks of
      dialysis, the morphology of the peritoneum was studied. RESULTS: In rats exposed
      to dialysis fluid supplemented with NAG, peritoneal permeability to creatinine
      and proteins was reduced when compared to animals dialyzed with glucose solution.
      In NAG treated animals, staining with alcian blue for polyanions in the
      peritoneal interstitium was significantly stronger than in rats dialyzed with
      glucose solution. CONCLUSIONS: Chronic peritoneal dialysis with dialysis solution
      supplemented with N-acetylglucosamine causes accumulation of glycosaminoglycans
      in the peritoneal interstitium, which results in a change of peritoneal
      permeability.

PMID- 9576373
TI  - Proteolipid in peritoneal effluent of CAPD patients.

PMID- 9576374
TI  - Formaldehyde in heat sterilized peritoneal dialysis solutions: scavenging system
      for its removal.

PMID- 9576375
TI  - Subcutaneous swelling during CAPD.

PMID- 9576377
TI  - Indium-111 oxine leukocyte scan in the diagnosis of peritoneal catheter tunnel
      infections.

PMID- 9576376
TI  - Treatment of CAPD peritonitis with intraperitoneal ampicillin/sulbactam
      aminoglycoside combination.

PMID- 9576378
TI  - Literature. March-April 1998.

PMID- 9576379
TI  - Nursing application: studies of peritoneal absorption and membrane
      characteristics.

PMID- 9576380
TI  - A survey about management of febrile children without source by primary care
      physicians.
AB  - BACKGROUND: The management of young children with fever without source is
      controversial, and differences between physician specialties have been noted
      previously. The emergence of penicillin-resistant Streptococcus pneumoniae, the
      sharp decline in invasive Haemophilus influenzae infections in immunized
      populations and publication of practice guidelines have potentially altered
      physician practices. OBJECTIVE: To determine the present practice preferences of
      pediatricians, family medicine physicians (FP) and emergency medicine physicians
      (EP). METHODS: We mailed a checklist survey to 1600 randomly selected
      pediatricians, family medicine practitioners (FP) and emergency medicine
      physicians (EP) in the United States and replicated the methodology of a
      1991/1992 survey. Physicians were asked about their evaluation and management of
      children of various ages (3 weeks, 7 weeks, 4 months and 16 months) with fever
      without source. RESULTS: Most primary care physicians would admit the 3- and 7
      week-old infants. For the 4-month-old infant 59% of EP, 45% of pediatricians and
      28% of FP would give empiric antibiotic(s) as an outpatient (P=0.005 for FP
      compared with pediatricians and P=0.02 for EP compared with pediatricians). The
      majority of physicians would manage the 16-month-old child as an outpatient
      without antibiotic therapy. Ceftriaxone was the preferred antibiotic for
      outpatient empiric therapy. There was a 3-fold increase (28% vs. 9%) for
      pediatricians in the use of empiric outpatient antibiotics for the 7-week-old
      infant in the present survey compared with the 1991/1992 survey. CONCLUSIONS:
      Physicians in the United States generally agree in their management of the young
      febrile infant, but with increasing patient age there is considerable variation.
      FP were the least aggressive in their evaluation and EP were the most aggressive.

PMID- 9576381
TI  - The use of Streptococcus pneumoniae nasopharyngeal isolates from healthy children
      to predict features of invasive disease.
AB  - BACKGROUND: The role of sampling nasopharyngeal carriage isolates of
      Streptococcus pneumoniae to determine characteristics of isolates causing
      invasive disease has not been established. METHODS: Data were compared from two
      1995 studies of S. pneumoniae in Metropolitan Toronto and Peel Region
      (population, 3.1 million). The first was a prospective survey of nasopharyngeal
      (NP) carriage in child care centers. The second was a prospective surveillance
      for all cases of invasive disease. RESULTS: There were 545 NP S. pneumoniae
      isolates obtained from 532 children and 96 cases of invasive S. pneumoniae
      disease in children. The prevalences of reduced antibiotic susceptibility in the
      NP carriage and invasive studies, respectively, were: penicillin (16% vs. 11%,
      P=0.29); erythromycin (12% vs. 7%, P=0.25); and multiresistant (16% vs. 12%,
      P=0.34). The power to rule out a difference between the groups was <30% for each
      comparison. Trimethoprim/sulfamethoxazole resistance was more common in NP
      carriage isolates than invasive isolates (38% vs. 23%, P=0.02). Serotype 14 was
      more common in invasive isolates, whereas serogroup 6 was more common in NP
      carriage isolates. Antibiotic-resistant isolates were predominantly serogroups 6,
      19 and 23 in both studies. CONCLUSIONS: Nasopharyngeal carriage isolates of S.
      pneumoniae reflect the antibiotic susceptibility rates of invasive isolates found
      in the same period for most antibiotics. However, even a large study like this
      may have limited power to detect a difference. The most common NP carriage
      serotypes are the same as the invasive isolates, although the rank order of
      specific serotypes is different. Routine surveys of S. pneumoniae NP carriage are
      not feasible because of the cost of serotyping and limited power of the
      observations, unless sample sizes are extremely large.

PMID- 9576382
TI  - Epidemiology of invasive pneumococcal infections in infants and young children in
      Metropolitan Santiago, Chile, a newly industrializing country.
AB  - AIM: To study the epidemiology of invasive pneumococcal infections in infants and
      young children in Santiago, Chile, as a representative pediatric population in a
      newly industrializing country where pneumococcal conjugate vaccines may be used
      in the future. METHODS: A 5-year retrospective laboratory-based review (1989 to
      1993) was followed by a 3-year prospective laboratory and hospital surveillance
      study in two of the six health administrative areas of Santiago to detect all
      hospitalized cases of invasive pneumococcal disease (defined as Streptococcus
      pneumoniae isolated from blood, cerebrospinal fluid or another normally sterile
      site) among infants and children (0 to 23 months of age in the retrospective and
      0 to 59 months of age in the prospective study). RESULTS: During the 5-year
      retrospective survey the incidence of invasive pneumococcal disease was 90.6
      cases per 10(5) infants 0 to 11 months old and 18.5 cases per 10(5) toddlers 12
      to 23 months old. Similar rates (60.2 per 10(5) infants and 18.1 per 10(5)
      toddlers) were recorded during the 3 years of prospective surveillance. Among the
      110 cases in children 0 to 59 months of age detected during the 3-year
      prospective surveillance, 2 clinical forms, pneumonia and meningitis, accounted
      for 87.2% of all cases; 13 of the 49 pneumonia patients (26%) had empyema as a
      complication. Notably 40 of the 110 cases (36.4%) occurred before 6 months of age
      (63.4% of the 63 infant cases). Serotypes 1, 14, 5 and 6B were the most
      prevalent. Overall 76 and 69%, respectively, of S. pneumoniae isolates were
      antigenic types that would be covered by the 11- or 9-valent conjugate vaccines
      under development. CONCLUSIONS: Invasive pneumococcal infections in Santiago,
      Chile, exhibit an epidemiologic pattern intermediate between that of developing
      and industrialized countries. The high burden of disease in early infancy
      dictates that an accelerated immunization schedule (beginning in the perinatal
      period) or maternal immunization with pneumococcal vaccines should be explored.

PMID- 9576384
TI  - Microbiology of acute arthropathies among children in Argentina: Mycoplasma
      pneumoniae and hominis and Ureaplasma urealyticum.
AB  - OBJECTIVE: To describe the isolation of mycoplasmas and ureaplasmas from synovial
      fluid in pediatric patients with joint disorders. METHODS: During 1 year 45
      samples of synovial fluid, blood and urine were collected from 33 hospitalized
      pediatric patients up to 17 years old who had joint disorders. Mycoplasmas and
      ureaplasmas were isolated in joint fluid by culture methods. RESULTS: Of the 33
      patients 12 (36%) had joint disorders associated with pathogens (bacteria,
      Mycoplasma/Ureaplasma, Chlamydia) present at the site of inflammation. Mycoplasma
      hominis and Ureaplasma urealyticum were isolated from 3 and 1% of joint fluid
      samples, respectively. M. pneumoniae was isolated from nasopharyngeal secretion
      in a patient with evidence of a reactive arthritis. CONCLUSION: Our results raise
      the question of the possible role of Mycoplasma as a cofactor in the triggering
      of inflammatory joint disease, as well as the hypothesis that arthropathies may
      be caused by chronic local infection. These findings may contribute to early
      diagnosis of the disease and initiation of specific treatment.

PMID- 9576383
TI  - Clinical acceptability and immunogenicity of a pentavalent parenteral combination
      vaccine containing diphtheria, tetanus, acellular pertussis, inactivated
      poliomyelitis and Haemophilus influenzae type b conjugate antigens in two-, four-
      and six-month-old Chilean infants.
AB  - BACKGROUND: In recent years additional parenteral vaccines have been recommended
      for routine immunization of infants in the US and elsewhere. The ability to
      administer multiple vaccines as a single injection without unacceptably
      increasing reactogenicity or decreasing immunogenicity of any component would
      offer many practical advantages. METHODS: A randomized, open, controlled trial
      was conducted to assess the tolerance profile and immunogenicity, as well as to
      identify potential antigenic interferences, resulting from administration of a
      parenteral combination vaccine for infants. The vaccine contains diphtheria and
      tetanus toxoids, acellular pertussis antigens (DTaP), enhanced inactivated
      poliovirus (eIPV) and Haemophilus influenzae type b-tetanus toxoid conjugate (PRP
      T). Infants (n=711) were randomly assigned to receive 1 of 5 regimens as the
      primary series at 2, 4 and 6 months of age, by group: (1) DTaP plus oral polio
      vaccine (OPV); (2) DTaP plus eIPV (separate injections); (3) DTaP-eIPV combined
      as a single injection; (4) DTaP-eIPV combined, plus a separate injection of PRP
      T; or (5) DTaP-eIPV combined and reconstituting PRP-T, as a single injection. At
      3, 5 and 7 months Groups 1, 2 and 3 received PRP-T. At 12 months all infants
      received a booster dose of DTaP reconstituting PRP-T as a single injection, plus
      a separate injection of measles, mumps and rubella vaccine. Groups 2, 3, 4 and 5
      received OPV at 7 months, and all infants received OPV at 13 months. Serum immune
      responses were measured to the primary series at 2 and 7 months and to the
      booster dose at 12 and 13 months. RESULTS: Reaction rates were similar among
      groups. In the primary series combining eIPV with DTaP decreased geometric mean
      titers (GMTs) to diphtheria, tetanus and pertussis. In addition concomitant PRP-T
      (either simultaneous or combined) with DTaP-eIPV lowered anti-PRP and further
      decreased tetanus GMTs. Nonetheless in 100% of infants protective titers were
      achieved against diphtheria and tetanus (>0.01 IU/ml each) and against the
      poliovirus types 1, 2 and 3 after eIPV (Groups 2 to 5); 99% of infants (Groups 4
      and 5) had protective titers against PRP (> or = 0.15 microg/ml). After boosting
      with DTaP/PRP-T decreased GMTs to diphtheria and PRP antigens were observed in
      the groups that received DTaP and eIPV combined. Nonetheless protective titers to
      diphtheria, tetanus and PRP occurred consistently. In contrast concomitant PRP-T
      with DTaP-eIPV enhanced the pertussis GMTs. CONCLUSIONS: We conclude that
      combined DTaP, eIPV and PRP-T in a single injection is well-tolerated and elicits
      an acceptable immune response to each component.

PMID- 9576385
TI  - A polymerase chain reaction for the diagnosis of Haemophilus influenzae type b
      disease in children and its evaluation during a vaccine trial.
AB  - BACKGROUND: Determination of the etiology of pneumonia in young children is
      difficult because blood culture, the usual method of diagnosis, is positive in
      only a small proportion of cases. For this reason vaccine trials that include
      bacterial pneumonia as an endpoint must be large. OBJECTIVES: To determine
      whether a diagnostic test based on a polymerase chain reaction could be used as
      an alternative to conventional blood culture for diagnosis of invasive
      Haemophilus influenzae type b (Hib) infections in young children investigated
      during the course of a large vaccine trial. METHODS: DNA was extracted from blood
      culture supernatants and probed for the presence of Hib DNA with a PCR assay with
      primers derived from the cap gene locus of Hib. Results of the PCR assay were
      compared with those obtained by conventional culture techniques. RESULTS: Blood
      cultures were obtained from 1544 children with suspected pneumonia, meningitis or
      septicemia and from 31 healthy control children who were contacts of cases. Blood
      culture supernatants were tested for Hib DNA in the PCR test. The sensitivity and
      specificity of a positive PCR test in blood culture supernatant as against
      culture of Hib from any normally sterile site were 100 and 99%, respectively.
      Eleven children had positive Hib PCR tests on blood culture supernatants but were
      negative by culture. In one of these cases Hib was isolated from a lung aspirate
      and in two other patients H. influenzae strains other than Hib were obtained from
      the cerebrospinal fluid. Eight of these 11 children were in the control group.
      When the results of the PCR assay were used to determine vaccine efficacy, a
      value of 86% was obtained compared with a figure of 95% obtained when
      conventional culture techniques were used. CONCLUSIONS: An Hib PCR assay on blood
      culture supernatants proved to be sensitive and specific for the diagnosis of Hib
      disease in children. The distribution of PCR-positive, culture-negative cases
      between Hib-vaccinated and control groups paralleled that of culture-positive
      cases, suggesting that most of these children had been infected with Hib. A trial
      of a highly efficacious vaccine provides a novel way for evaluating new
      diagnostic tests for which there is no standard diagnostic test of 100%
      reliability.

PMID- 9576386
TI  - Loss maternally derived measles immunity in Argentinian infants.
AB  - BACKGROUND: Measles immunization of children at 1 year of age with a single dose
      of the current vaccine has successfully reduced measles incidence in Argentina.
      However, the optimal schedule of measles vaccination of young infants would
      balance the risk of early loss of maternal antibody in the majority of infants
      with the risk of primary vaccine failure because of passive measles immunity.
      This study is the first to document a significant association between loss of
      passive measles antibody and age among infants born in 1995 and 1996 in Cordoba
      City, Argentina. METHODS: This is a seroprevalence study of 340 infants to
      investigate the duration of transplacentally derived measles antibody, assayed by
      a neutralization test, during the first 8 months of age in Cordoba City,
      Argentina. RESULTS: The proportion with detectable neutralizing measles
      antibodies decreased from 85% at 1 month of age to 8% at 8 months of age. The
      simple logistic model with age (in weeks) as the only variable showed that the
      decline in the proportion of infants with a positive antibody titer was sharpest
      during the second and fifth months of age (6.6 and 6.8% per week during a 4-week
      period, respectively). CONCLUSIONS: These findings suggest that 80% of infants
      are susceptible to measles infection for at least 3 months before routine
      immunization at 12 months of age.

PMID- 9576387
TI  - Effectiveness of prenatal tetanus toxoid immunization against neonatal tetanus in
      a rural area in India.
AB  - BACKGROUND: Neonatal tetanus is the cause of 23 to 73% of neonatal deaths in
      developing countries and continues to be an important killer in many parts of
      India. METHODS: In this nonrandomized cohort study in a rural area in India,
      tetanus toxoid immunization status was recorded for 1688 pregnant women. Liveborn
      children were followed up for 30 days for the occurrence of neonatal tetanus.
      Nonimmunized and partially immunized women were asked their reasons for not
      receiving tetanus toxoid vaccine. RESULTS: Complete prenatal immunization with
      tetanus toxoid during pregnancy (two doses 1 month apart) was associated with an
      88% reduction in the risk of neonatal tetanus among the newborn children [95%
      confidence interval (CI) 59 to 98%]. In multivariable analysis only complete
      immunization and the use of clean instruments for cutting the umbilical cord were
      independently associated with a reduction in risk of neonatal tetanus.
      Registration by the health care provider before 29 weeks of gestation, being 5 km
      or less from the vaccination facility, having two or more contacts with the
      health provider and having some school education were independently associated
      with complete immunization. CONCLUSIONS: Immunization of pregnant women with
      tetanus toxoid was the single most effective intervention against neonatal
      tetanus independent of other interventions.

PMID- 9576388
TI  - Ureaplasma urealyticum respiratory tract colonization is associated with an
      increase in interleukin 1-beta and tumor necrosis factor alpha relative to
      interleukin 6 in tracheal aspirates of preterm infants.
AB  - OBJECTIVE: To determine whether Ureaplasma urealyticum respiratory tract
      colonization in very low birth weight infants during the first week of life is
      associated with changes in tracheal aspirate concentrations of the cytokines
      interleukin 1-beta (IL-1-beta), tumor necrosis factor alpha (TNF-alpha) and IL-6.
      METHODS: Infants with birth weights < or =1250 g were prospectively enrolled.
      Samples were obtained from the endotracheal tube or nasopharynx on Day 1 and
      again between Days 7 and 10 for U. urealyticum culture. The concentrations of IL
      1-beta, TNF-alpha and IL-6 were measured in tracheal aspirate samples by enzyme
      linked immunosorbent assay. RESULTS: There were 18 positive cultures for U.
      urealyticum from 15 of 96 infants (15.6%). IL-1-beta in tracheal aspirates
      expressed as concentration per volume or as a ratio of IL-1-beta to IL-6 were 7-
      and 14.9-fold higher, respectively, in Ureaplasma-positive infants than in
      Ureaplasma-negative infants (P < 0.05). The TNF-alpha/IL-6 ratio was 18.9 and
      15.5 times higher in the Ureaplasma-positive aspirates than in the Ure aplasma
      negative aspirates on Day 1 and Days 7 to 10 (P < 0.05). Concentrations of IL-1
      beta and TNF-alpha were significantly correlated on Day 1 and Days 7 to 10.
      Although there was no clinical association demonstrated between U. urealyticum
      colonization and the development of bronchopulmonary dysplasia (BPD) in this
      study, infants who developed BPD had significantly higher IL-1-beta
      concentrations and ratios of IL-1-beta to IL-6 in Day 1 aspirates than infants
      who did not develop BPD. Conclusions. Isolation of U. urealyticum from the
      respiratory tract is associated with increased IL-1-beta concentrations and IL-1
      beta-IL-6 ratios on Day 1 and increased TNF-alpha-IL-6 ratios on Days 1 and 7 to
      10 in tracheal aspirates of colonized infants. Infants who developed BPD had
      higher IL-1-beta concentrations and IL-1-beta-IL-6 ratios, suggesting that these
      may be early markers of lung inflammation.

PMID- 9576389
TI  - Molecular epidemiology of staphylococcal scalded skin syndrome in premature
      infants.
AB  - BACKGROUND: Outbreaks of nosocomial staphylococcal scalded skin syndrome (SSSS)
      in infants have been well-described associated with the well baby nursery or
      delivery room. We describe two cases of SSSS in very low birth weight infants in
      a neonatal intensive care unit (NICU) and the success of infection control
      strategies used to prevent an outbreak. METHODS: Staphylococcal scalded skin
      syndrome was diagnosed in two infants in the NICU: Case I (a 47-day-old, formerly
      530-g female); and Case II diagnosed 48 h later (a 41-day old, formerly 706-g
      female). Multiple infection control measures were implemented: (1) isolation and
      intravenous antibiotic treatment of cases; (2) placement of exposed infants into
      a cohort; (3) prophylactic mupirocin treatment of the anterior nares of all
      infants in the NICU and staff colonized with Staphylococcus aureus; and (4)
      personnel hand washing with hexachlorophene. Detection of exfoliative toxin A and
      studies to determine the genetic relatedness of S. aureus strains isolated from
      patients and staff were performed. RESULTS: In addition to the two SSSS cases, S.
      aureus was isolated from 2 of 12 (17%) exposed asymptomatic infants, 2 of 20
      (10%) ancillary staff, 8 of 30 (27%) nurses and 6 of 24 (25%) physicians.
      Exfoliative toxin A-producing strains were isolated from both cases and one
      asymptomatic infant. No toxin was expressed by strains isolated from staff. Pulse
      field gel electrophoresis demonstrated genetically identical strains of S. aureus
      from the two SSSS cases and the asymptomatic infant, whereas three staff members
      harbored strains genetically related to the case strain. Unexpectedly two
      additional unique clusters of genetically related S. aureus strains were
      identified from the surveillance cultures. CONCLUSIONS: This report documents the
      rare occurrence of nosocomial SSSS attributed to transmission in the NICU among
      extremely low birth weight infants. Multiple infection control strategies were
      effective in limiting the outbreak. Molecular epidemiology investigation
      supported a unique S. aureus strain responsible for this event and the presence
      of bidirectional spread between staff and patients of non-toxin-producing
      strains.

PMID- 9576390
TI  - Symptoms associated with rhesus-human reassortant rotavirus vaccine in infants.
AB  - BACKGROUND: Severe rotavirus gastroenteritis is potentially preventable by oral
      rhesus-human reassortant tetravalent (RRV-TV) vaccine, which may soon be licensed
      in the US and Europe. The objective of this study was to evaluate symptoms
      associated with the high titer RRV-TV vaccine given concurrently with routine
      childhood immunizations. METHODS: In a randomized placebo-controlled double blind
      trial of RRV-TV vaccine titer 4 x 10(5) plaque-forming units vs. placebo, 2282
      children received all 3 doses of study vaccine between ages 2 and 7 months.
      Symptoms were followed by parents who also took daily rectal temperatures.
      RESULTS: On Days 3 to 5 after the first dose of vaccine fever 38.0 degrees C or
      greater was detected in 387 of 1182 (33%) infants in the RRV-TV vaccine group vs.
      27 of 1194 (2.3%) infants in the placebo group (P < 0.001) and fever 39.0 degrees
      C or greater was detected in 40 (3.4%) and 3 (0.2%) infants in the vaccine and
      placebo groups, respectively (P < 0.001). Irritability, decreased appetite and
      abdominal cramping on Days 3 to 5 postvaccination were also more common in the
      RRV-TV vaccine recipients than in the placebo recipients. One child in the RRV-TV
      group was hospitalized and 2 more infants seen in the clinic, vs. none in the
      placebo group, within the 5-day period after the first dose for a reason probably
      related to the RRV-TV vaccine. After the second and third doses of RRV-TV
      vaccine, there were only minor differences between the vaccine and placebo
      recipients in fever on Days 3 to 5 postvaccination. CONCLUSIONS: The first dose
      of RRV-TV vaccine is associated with a relatively high rate of febrile and other
      reactions, which may require a physician visit and, rarely, hospitalization.

PMID- 9576391
TI  - Adjunctive therapy in cystic firbrosis (CF).

PMID- 9576392
TI  - Malaria: update on treatment.

PMID- 9576393
TI  - Neurologic manifestations of infection with HIV.

PMID- 9576394
TI  - Cytomegalovirus retinitis after transplantation of positively selected CD34+
      cells from HLA-mismatched donors.

PMID- 9576395
TI  - Infected stingray injury.

PMID- 9576396
TI  - Rapid detection of group A streptococcal antigen with a new optical immunoassay.

PMID- 9576397
TI  - Monitoring serum vancomycin concentrations in children: is it necessary?

PMID- 9576398
TI  - Concomitant viral and Bordetella pertussis infections in infants.

PMID- 9576399
TI  - Pneumatosis intestinalis in pediatric acquired immunodeficiency syndrome.

PMID- 9576400
TI  - Properdin deficiency: rare presentation with meningococcal bone and joint
      infections.

PMID- 9576402
TI  - The clinical philosophy of internal medicine.

PMID- 9576401
TI  - Isolation of group A streptococci from children with perianal cellulitis and from
      their siblings.

PMID- 9576403
TI  - The clinical philosophy of family medicine.

PMID- 9576404
TI  - The clinical philosophy of medicine-pediatrics.

PMID- 9576405
TI  - Anticardiolipin antibodies predict early recurrence of thromboembolism and death
      among patients with venous thromboembolism following anticoagulant therapy.
      Duration of Anticoagulation Study Group.
AB  - PURPOSE: To compare the risk of recurrent venous thromboembolism in patients with
      and without antiphospholipid antibodies. PATIENTS AND METHODS: Anticardiolipin
      antibodies were tested 6 months after a first or second episode of venous
      thromboembolism. Of the patients with a first episode of venous thromboembolism
      only the 412 who received 6 months of anticoagulation were studied. Two hundred
      and eleven patients with a second episode received oral anticoagulation for 6
      months or indefinitely. The therapy was targeted at an international normalized
      ratio (INR) of 2.0 to 2.85. All patients were followed up for 4 years after
      enrollment. RESULTS: Among the 412 patients with a first episode of venous
      thromboembolism the risk of recurrence was 29% in patients with anticardiolipin
      antibodies and 14% in those without antibodies (P = 0.0013). In those with
      antibodies, there was an increased risk during the first 6 months after cessation
      of anticoagulation. The risk of recurrence increased with the titer of the
      antibodies. Four-year mortality rate was 15% in those with antibodies and 6% in
      those without (P = 0.01). Among 34 patients with a second event of venous
      thromboembolism and anticardiolipin antibodies, there were no recurrences during
      anticoagulant therapy versus 20% in those who received only 6 months of treatment
      (P = 0.08). CONCLUSIONS: The presence of elevated titers of anticardiolipin
      antibodies 6 months after an episode of venous thromboembolism is a predictor for
      an increased risk of recurrence and of death. Patients with anticardiolipin
      antibodies and venous thromboembolism seem to benefit from prolonged oral
      anticoagulation.

PMID- 9576406
TI  - A randomized trial of captopril for microalbuminuria in normotensive adults with
      sickle cell anemia.
AB  - PURPOSE: Nephropathy is a common complication of sickle cell anemia and is often
      preceded by proteinurea. Our aim was to evaluate the effect of angiotensin
      converting enzyme inhibition on microalbuminuria in sickle cell patients.
      PATIENTS AND METHODS: We performed a randomized, double-blind, placebo-controlled
      trial in 22 normotensive patients with sickle cell anemia and persistent
      microalbuminuria. Patients received captopril (25 mg/day) or placebo and were
      followed up for 6 months. Albuminuria, blood pressure, and serum creatinine and
      hemoglobin concentrations were measured at baseline and at 1, 3, and 6 months.
      The primary outcome variable was the 6-month change in albuminuria between the
      two groups. RESULTS: Baseline albuminuria was 121 (SD 66) mg per 24 hours in the
      captopril group and 107 (SD 86) mg per 24 hours in the placebo group.
      Microalbuminuria decreased from baseline in the captopril group but increased in
      the placebo group. The mean absolute change and the mean percentage change in
      microalbuminuria were significantly different between the two groups at 6 months
      (absolute change -45 mg per 24 hours in the captopril group versus +18 mg per 24
      hours in the placebo group, P <0.01; and percentage change -37% in the captopril
      group versus +17% in the placebo group, P <0.01). The 95% confidence intervals
      (CI) for the difference in albuminuria between the two groups were 63 (CI 40 to
      86) mg per 24 hours for the mean absolute change and 54% (CI 22% to 85%) for the
      mean percentage change. Blood pressure decreased slightly from baseline in
      captopril-treated patients and did not change in the placebo group. The change
      was significantly different between the two groups only for diastolic blood
      pressure at 6 months (P <0.01). CONCLUSION: Captopril reduces albuminuria and
      slightly decreases blood pressure in patients with sickle cell anemia. More
      studies are required to demonstrate the sustained benefit on protein excretion.

PMID- 9576407
TI  - Independent association between acute renal failure and mortality following
      cardiac surgery.
AB  - PURPOSE: To determine whether there is an independent association of acute renal
      failure requiring dialysis with operative mortality after cardiac surgery.
      PATIENTS AND METHODS: The 42,773 patients who underwent coronary artery bypass or
      valvular heart surgery at 43 Department of Veterans Affairs Medical Centers
      between 1987 and 1994 were evaluated to determine the association between acute
      renal failure sufficient to require dialysis and operative mortality, with and
      without adjustment for comorbidity and postoperative complications. Crude and
      adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were derived from
      logistic regression analysis. RESULTS: Acute renal failure occurred in 460 (1.1%)
      patients. Overall operative mortality was 63.7% in these patients, compared with
      4.3% in patients without this complication. The unadjusted OR for death was 39
      (95% CI 32 to 48). After adjustment for comorbid factors related to the
      development of acute renal failure (surgery type, baseline renal function,
      preoperative intraaortic balloon pump, prior heart surgery, NYHA class IV status,
      peripheral vascular disease, pulmonary rales, left ventricular ejection fraction
      below 35%, chronic obstructive pulmonary disease, systolic blood pressure, and
      the cross-product of systolic blood pressure and surgery type), the OR was 27
      (95% CI 22 to 34). Further adjustment was made for seven postoperative
      complications (low cardiac output, cardiac arrest, perioperative myocardial
      infarction, prolonged mechanical ventilation, reoperation for bleeding or repeat
      cardiopulmonary bypass, stroke or coma, and mediastinitis), that were
      independently associated with operative mortality. The OR adjusted for
      comorbidity and postoperative complications associated with acute renal failure
      was 7.9 (95% CI 6 to 10). CONCLUSIONS: Acute renal failure was independently
      associated with early mortality following cardiac surgery, even after adjustment
      for comorbidity and postoperative complications. Interventions to prevent or
      improve treatment of this condition are urgently needed.

PMID- 9576408
TI  - Gastrointestinal bleeding in the hospitalized patient: a case-control study to
      assess risk factors, causes, and outcome.
AB  - PURPOSE: To determine the risk factors, etiology, and outcome of clinically
      important gastrointestinal bleeding that occurs after hospital admission
      (nosocomial gastrointestinal bleeding). PATIENTS AND METHODS: Cases consisted of
      consecutive patients who developed gastrointestinal bleeding more than 24 hours
      after admission to the hospital. Cases were compared with two control
      populations: a set of hospitalized patients without gastrointestinal bleeding
      matched with cases for age, gender, and length of stay; and all patients admitted
      to the hospital with clinically important gastroduodenal ulcer bleeding during
      the study period. Case and controls were compared with respect to risk factors
      for gastrointestinal bleeding and outcomes. Data were obtained through a
      comprehensive review of medical records. RESULTS: Clinically important nosocomial
      gastrointestinal bleeding occurred in 67 inpatients after a mean hospital length
      of stay of 14 +/- 10 days. The majority (64%) of the patients were not
      hospitalized in the intensive care unit at the onset of the bleeding. Seventy-two
      percent of the patients who developed bleeding had been receiving some form of
      bleeding prophylaxis. In a multivariate analysis, a prior intensive care unit
      stay (odds ratio 2.5; 95% confidence interval 1.0 to 6.1; P <0.05) and mechanical
      ventilation (OR 3.4; 95% CI 1.1 to 10.7; P = 0.03) were independent risk factors
      for the onset of bleeding. Nosocomial gastrointestinal bleeding was associated
      with poor outcome, with an associated mortality of 34%. Duodenal ulcer disease
      was the most common source of nosocomial gastrointestinal bleeding, accounting
      for 36% of cases overall. Nosocomial ulcer bleeders were less likely to have a
      previous history of ulcer disease (13% versus 50%; P <0.05) Helicobacter pylori
      infection (14% versus 62%; P <0.0001), chronic active gastritis (29% versus 91%;
      P <0.0001), or to be taking NSAIDs (48% versus 68%; P <0.08) than patients
      admitted to the hospital with ulcer bleeding. CONCLUSIONS: Gastrointestinal
      bleeding remains an important complication of hospitalization, with a high
      associated mortality. Our current approaches to prevention of this complication
      are imperfect. Bleeding tends to occur after a prolonged hospital stay and is
      more likely to occur in patients with more severe underlying illnesses. Duodenal
      ulcer disease is the most common source of this bleeding. Nosocomial
      gastroduodenal ulcer disease is distinct in etiology from the ulcer disease that
      occurs in outpatients.

PMID- 9576409
TI  - Thrombocytopenia, giant platelets, and leukocyte inclusion bodies (May-Hegglin
      anomaly): clinical and laboratory findings.
AB  - PURPOSE: May-Hegglin anomaly is a rare hereditary condition characterized by the
      triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes.
      Clinical features and the pathogenesis of bleeding in this disease are poorly
      defined. PATIENTS AND METHODS: From 1988 to 1996 we studied 15 new May-Hegglin
      anomaly patients from 7 unrelated Italian families. In addition to clinical
      examination and routine laboratory testing, we measured bleeding time, platelet
      aggregation and release reaction, and platelet staining for tubulin, and
      performed ultrastructural study of polymorphonuclear leukocytes. RESULTS:
      Although the mean age of our patients was 33 years, May-Hegglin anomaly had not
      been previously recognized in any of them. Bleeding diatheses ranged from severe
      to absent, and platelet count from 26 to 178 x 10(9)/L. No correlation was found
      between bleeding tendency and platelet count. Previous therapy with
      corticosteroids, high-dose immunoglobulins, and splenectomy had no effect on
      platelet count or bleeding diathesis. Desmopressin infusion greatly shortened the
      bleeding time in the most severely affected patient. The in vitro function of
      platelets was normal except for the absence of shape change in all subjects and
      defective response to epinephrine in 8 of 15 patients. Platelet tubulin was
      distributed unevenly instead of being organized in a circumferential band at the
      cell periphery. CONCLUSION: The diagnosis of May-Hegglin is easily missed, and
      its frequency is probably underestimated. A qualitative defect of platelets may
      be responsible for mild bleeding diathesis even in the absence of
      thrombocytopenia, while severe bleeding results from both qualitative and
      quantitative platelet defects. May-Hegglin anomaly should be suspected whenever a
      patient has a low platelet count or a bleeding diathesis of unknown origin.

PMID- 9576410
TI  - What proportion of common diagnostic tests appear redundant?
AB  - PURPOSE: To identify ancillary tests for which there are criteria defining the
      earliest interval at which a repeat test might be indicated, to determine how
      often each test is repeated earlier than these intervals and, if repeated,
      provides useful information. SUBJECTS AND METHODS: We performed a retrospective
      cohort study of 6,007 adults discharged from a large teaching hospital during a 3
      month period in 1991. We measured the proportion of commonly performed diagnostic
      tests that were redundant, and their associated charges. RESULTS: Of the 6,007
      patients discharged, 5,289 (88%) had at least one of 12 target tests performed.
      Overall, 78,798 of the target tests were performed during the study period, of
      which 22,237 (28%) were repeated earlier than test-specific predefined intervals.
      This percentage varied substantially by test (range, 2% to 62%). To assess how
      many early repeats were justified, we performed chart reviews in a random sample
      stratified by test. For two tests, nearly all the initial results in the sample
      were abnormal, and all repeats were considered justified. Of early repeats
      following a normal initial result for the remaining 10 tests, chart review found
      no clinical indication for 92%, and a weighted mean of 40% appeared redundant.
      Overall, 8.6% of these 10 tests appeared redundant; if these were not performed,
      the annual charge reductions would be $930,000 at our hospital, although the
      impact on costs would be much smaller. CONCLUSIONS: For some tests, an important
      proportion are repeated too early to provide useful clinical information. Most
      such tests might be eliminated using computerized reminder systems.

PMID- 9576411
TI  - The influence of chronic prearrest health conditions on mortality and functional
      neurological recovery in cardiac arrest survivors.
AB  - PURPOSE: To study the impact of chronic prearrest health conditions on mortality
      and neurological recovery in patients after witnessed cardiac arrest and primary
      successful resuscitation. PATIENTS AND METHODS: The study was set in the
      community of Vienna, Austria. Data concerning cardiopulmonary resuscitation of
      adult patients who survived a witnessed cardiac arrest were collected according
      to an internationally recommended protocol (Utstein-Style). Chronic prearrest
      health conditions and New York Heart Association (NYHA) functional classes were
      evaluated. All patients were followed up for 6 months after the event or death.
      Adverse outcome was defined as death or severe neurological impairment. A forward
      stepwise logistic regression model was applied to assess the impact of pre-arrest
      morbidity on unfavorable outcome, expressed as odds ratio (OR) with 95%
      confidence intervals (CI). RESULTS: Of 411 patients, 269 (66%) had one or more of
      the following pre-arrest diseases: coronary heart disease (45%), hypertension
      (26%), congestive heart failure (20%), diabetes mellitus (14%), chronic pulmonary
      disease (6%), and cerebrovascular disease (5%). In 22% a NYHA class of III or IV
      was present before cardiac arrest. At 6-month follow-up, 161 (40%) of the
      patients were alive with favorable neurological recovery; overall mortality was
      57% (n = 233). Increasing NYHA classes (OR 1.4 per NYHA class increase; CI 1.1 to
      1.7) and increasing age were independent predictors of adverse outcome (OR 1.03
      per 10-year increase; CI 1.01 to 1.05), as were durations of cardiac arrest (OR
      1.10 per 5-minute increase; CI 1.07 to 1.12) and the presence of ventricular
      fibrillation or tachycardia (OR 0.3; CI 0.2 to 0.5). The remaining health
      conditions, as listed above, were not independently associated with outcome.
      CONCLUSIONS: A large proportion of patients with cardiac arrest had chronic
      diseases before the event. The presence of impaired functional performance in
      patients with structural heart disease increased unfavorable outcome within 6
      months in primary cardiac arrest survivors. However, the impact of chronic
      prearrest conditions on outcome seems to be very small, and should not influence
      decisions whether to withhold or withdraw therapy.

PMID- 9576412
TI  - Academic calculations versus clinical judgments: practicing physicians' use of
      quantitative measures of test accuracy.
AB  - PURPOSE: To determine how often practicing physicians use the customarily
      recommended quantitative methods that include sensitivity, specificity, and
      likelihood ratio indexes; receiver operator characteristic (ROC) curves; and
      Bayesian diagnostic calculations. PARTICIPANTS AND METHODS: A random sample of
      300 practicing physicians (stratified by specialty to include family physicians,
      general internists, general surgeons, pediatricians, obstetrician/gynecologists,
      and internal medicine subspecialists) were briefly interviewed in a telephone
      survey. They were asked about the frequency with which they used the formal
      methods, the reasons for non-use, and if they employed alternative strategies
      when appraising tests' diagnostic accuracy. RESULTS: Of the 300 surveyed
      physicians, 8 (3%) used the recommended formal Bayesian calculations, 3 used ROC
      curves, and 2 used likelihood ratios. The main reasons cited for non-use included
      impracticality of the Bayesian method (74%), and nonfamiliarity with ROC curves
      and likelihood ratios (97%). Of the 174 physicians who said they used sensitivity
      and specificity indexes, 165 (95%) did not do so in the recommended formal
      manner. Instead, the physicians directly estimated tests' diagnostic accuracy by
      determining how often the test results were correct in groups of patients later
      found to have, or to be free of, the selected disease. CONCLUSIONS: The results
      indicate that most practicing physicians do not use the formal recommended
      quantitative methods to appraise tests' diagnostic accuracy, and instead report
      using an alternative direct approach. Although additional training might make
      physicians use the formal methods more often, the physicians' direct method
      merits further evaluation as a potentially pragmatic tool for the determination
      of tests' diagnostic accuracy in clinical practice.

PMID- 9576414
TI  - Cholera.

PMID- 9576413
TI  - Thrombotic storm: when thrombosis begets thrombosis.
AB  - Patients with hypercoagulability may present with a single thrombosis and
      subsequently develop progressive thromboses at other sites. With inadequate
      therapy, the thrombotic process may self-perpetuate, leading to multiple
      thromboses and even death. Six cases are presented demonstrating key features of
      what may be termed thrombotic storm: (1) an underlying hypercoagulable disorder;
      (2) a provocation to initiate thrombosis; (3) rapid development of new
      thromboses; (4) response to prompt use of thrombolytic agent or anticoagulant
      therapy; and (5) remarkable good long-term prognosis if the cycle of thrombosis
      is interrupted. Continued activation of coagulation by fresh thrombosis is
      hypothesized as the cause of the syndrome, which may explain its control by
      anticoagulants. Whereas these unusual patients' courses most likely represent
      only an extreme of hypercoagulability and not a new disorder, their
      characteristic behavior warrants attention.

PMID- 9576415
TI  - QT prolongation and Torsades de Pointes associated with clarithromycin.

PMID- 9576416
TI  - Diarrhea with ileal and hepatic abnormalities in a 52-year-old man.

PMID- 9576417
TI  - Stress ulcer bleeding: hopeful optimism.

PMID- 9576418
TI  - Diagnostic dilemma.

PMID- 9576419
TI  - Defibrillation aboard a commercial aircraft.

PMID- 9576420
TI  - Xenotransplantation.

PMID- 9576421
TI  - Success in failure: modeling cardiac decompensation in transgenic mice.

PMID- 9576422
TI  - Statin trials and goals of cholesterol-lowering therapy.

PMID- 9576423
TI  - Influence of pravastatin and plasma lipids on clinical events in the West of
      Scotland Coronary Prevention Study (WOSCOPS).
AB  - BACKGROUND: The West of Scotland Coronary Prevention Study was a primary
      prevention trial that demonstrated the effectiveness of pravastatin (40 mg/d) in
      reducing morbidity and mortality from coronary heart disease (CHD) in moderately
      hypercholesterolemic men. The present analysis examines the extent to which
      differences in LDL and other plasma lipids both at baseline and on treatment
      influenced CHD risk reduction. METHODS AND RESULTS: Relationships between
      baseline lipid concentrations and incidence of all cardiovascular events and
      between on-treatment lipid concentrations and risk reduction in patients taking
      pravastatin were examined by use of Cox regression models and by division of the
      cohort into quintiles. Variation in plasma lipids at baseline did not influence
      the relative risk reduction generated by pravastatin therapy. Fall in LDL level
      in the pravastatin-treated group did not correlate with CHD risk reduction in
      multivariate regression. Furthermore, maximum benefit of an approximately 45%
      risk reduction was observed in the middle quintile of LDL reduction (mean 24%
      fall); further mean decrements in LDL (up to 39%) were not associated with a
      greater decrease in CHD risk. Comparison of event rates between placebo- and
      pravastatin-treated subjects with the same LDL cholesterol level provided
      evidence for an apparent treatment effect that was independent of LDL.
      CONCLUSIONS: We conclude that the treatment effect of 40 mg/d of pravastatin is
      proportionally the same regardless of baseline lipid phenotype. There is no CHD
      risk reduction unless LDL levels are reduced, but a fall in the range of 24% is
      sufficient to produce the full benefit in patients taking this dose of
      pravastatin. LDL reduction alone does not appear to account entirely for the
      benefits of pravastatin therapy.

PMID- 9576424
TI  - Relationship between plasma LDL concentrations during treatment with pravastatin
      and recurrent coronary events in the Cholesterol and Recurrent Events trial.
AB  - BACKGROUND: Although LDL lowering has been shown to reduce recurrent coronary
      events in patients with coronary heart disease, little direct information is
      available on the extent of LDL lowering required to achieve this outcome. METHODS
      AND RESULTS: The Cholesterol and Recurrent Events (CARE) trial compared
      pravastatin and placebo in patients who had experienced myocardial infarction
      (MI) who had average concentrations of total cholesterol <240 mg/dL (baseline
      mean, 209 mg/dL) and LDL cholesterol (LDL) 115 to 174 mg/dL (mean, 139 mg/dL).
      Pravastatin reduced coronary death or recurrent MI by 24%. In multivariate
      analysis, the LDL concentration achieved during follow-up was a significant,
      although nonlinear, predictor of the coronary event rate (P=.007), whereas the
      extent of LDL reduction was not significant, whether expressed as an absolute
      amount (P=.97) or a percentage (P=.76). The coronary event rate declined as LDL
      decreased during follow-up from 174 to approximately 125 mg/dL, but no further
      decline was seen in the LDL range from 125 to 71 mg/dL. In multivariate analysis,
      triglyceride but not HDL concentrations during follow-up were weakly but
      significantly associated with the coronary event rate. CONCLUSIONS: The LDL
      concentrations achieved during treatment with pravastatin or placebo were
      associated with reduction in coronary events down to an LDL concentration of
      approximately 125 mg/dL. LDL concentrations <125 mg/dL during treatment were not
      associated with further benefit. Absolute or percentage reduction in LDL had
      little relationship to coronary events.

PMID- 9576425
TI  - Lipoprotein changes and reduction in the incidence of major coronary heart
      disease events in the Scandinavian Simvastatin Survival Study (4S)
AB  - BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444
      patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0
      mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to
      simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period
      of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of
      the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the
      simvastatin group (34% risk reduction, P<.00001). Simvastatin produced
      substantial changes in several lipoprotein components, which we have attempted to
      relate to the beneficial effects observed. METHODS AND RESULTS: The Cox
      proportional hazards model was used to assess the relationship between lipid
      values (baseline, year 1, and percent change from baseline at year 1) and MCEs.
      The reduction in MCEs within the simvastatin group was highly correlated with on
      treatment levels and changes from baseline in total and LDL cholesterol,
      apolipoprotein B, and less so with HDL cholesterol, but there was no clear
      relationship with triglycerides. We estimate that each additional 1% reduction in
      LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001).
      CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in
      individual patients in 4S was determined mainly by the magnitude of the change in
      LDL cholesterol, and they are consistent with current guidelines that emphasize
      aggressive reduction of this lipid in CHD patients.

PMID- 9576426
TI  - Association between body iron stores and the risk of acute myocardial infarction
      in men.
AB  - BACKGROUND: Epidemiological evidence concerning the role of iron, a lipid
      peroxidation catalyst, in coronary heart disease (CHD) is inconsistent. We
      investigated the association of the concentration ratio of serum transferrin
      receptor to serum ferritin (TfR/ferritin), a state-of-the-art measurement of body
      iron stores, with the risk of acute myocardial infarction (AMI) in a prospective
      nested case-control study in men from eastern Finland. METHODS AND RESULTS:
      Transferrin receptor assays were carried out for 99 men who had an AMI during an
      average 6.4 years of follow-up and 98 control men. Both the cases and the
      controls were nested from the Kuopio Ischemic Heart Disease Risk Factor Study
      (KIHD) cohort of 1931 men who had no clinical CHD at the baseline study. The
      controls were matched for age, examination year, and residence. AMIs were
      registered prospectively. Soluble transferrin receptors were measured by
      immunoenzymometric assay and ferritin concentration by radioimmunoassay from
      frozen baseline serum samples. The mean TfR/ferritin ratio was 15.1 (SE, 2.0)
      among cases and 21.3 (SE, 2.2) among controls (P=.035 for difference). In
      logistic regression models adjusting for other strongest risk factors for AMI and
      indicators of inflammation and alcohol intake, men in the lowest and second
      lowest thirds of the TfR/ferritin ratio had a 2.9-fold (95% CI, 1.3 to 6.6,
      P=.011) and 2.0-fold (0.9 to 4.2, P=.081) risk of AMI compared with men in the
      highest third (P=.010 for trend). CONCLUSIONS: These data show an association
      between increased body iron stores and excess risk of AMI, confirming previous
      epidemiological findings.

PMID- 9576427
TI  - Blood viscosity and elevated carotid intima-media thickness in men and women: the
      Edinburgh Artery Study.
AB  - BACKGROUND: Several hemostatic and rheological factors have been associated with
      incident cardiovascular events. However, there have been no reports on the
      relationship of rheological factors with early atherosclerosis and very few on
      hemostatic factors. We therefore studied the relationship between these factors
      and carotid intima-media thickness (IMT). METHODS AND RESULTS: The Edinburgh
      Artery Study measured fibrinogen, tissue plasminogen activator (tPA), fibrin D
      dimer, von Willebrand factor (vWF), blood and plasma viscosities, and hematocrit
      as part of its baseline examination during 1988-1989. At the 5-year follow-up,
      valid measurements of IMT had been recorded in 1106 men and women 60 to 80 years
      old. In men, blood viscosity (P< or =.001) and its major determinants, plasma
      viscosity, fibrinogen (both P< or =.01), and hematocrit (P< or =.05), were all
      linearly related to IMT. Furthermore, blood viscosity, fibrinogen (both P< or
      =.01), and plasma viscosity (P< or =.05) remained significantly associated on
      multivariate analysis. Correcting blood viscosity to a standard hematocrit of 45%
      had little effect on its association. In men, there was a significantly increased
      risk of having an IMT above versus below the upper quartile of its distribution
      (1.05 mm) for SD increases in blood viscosity (P< or =.01), fibrinogen, corrected
      blood viscosity, and plasma viscosity (all P< or =.05). With the exception of
      plasma viscosity, these risks were unaffected by adjustment for other common
      cardiovascular risk factors. No significant associations were found between any
      of the hemorheological factors and IMT in women or for tPA, fibrin D-dimer, or
      vWF in either sex. CONCLUSIONS: These findings suggest that in men, blood
      viscosity and its major determinants are associated not only with incident
      cardiovascular events but also with the early stages of atherosclerosis. This may
      be one explanation for the link between rheological factors and events.

PMID- 9576428
TI  - Role of dobutamine stress echocardiography in predicting outcome in 860 patients
      with known or suspected coronary artery disease.
AB  - BACKGROUND: Increasingly, dobutamine stress echocardiography has been used for
      detection of coronary artery disease. Less information exists regarding the
      incremental prognostic value of the test, including semiquantitative wall
      scoring, compared with clinical and rest echocardiographic variables. METHODS AND
      RESULTS: Follow-up information was obtained from 860 patients who underwent
      dobutamine stress echocardiography over a 2-year period. To determine the value
      of dobutamine stress echocardiography in predicting cardiac events, including
      cardiac death and myocardial infarction, clinical and rest and stress
      echocardiographic data were considered in a stepwise Cox multivariate regression
      model. During follow-up of up to 52 months, 72 patients underwent coronary
      revascularization before any cardiac event and were censored. Eighty-six patients
      had cardiac events, including nonfatal myocardial infarction in 36 and cardiac
      death in 50. In a multivariate model, a history of congestive heart failure, the
      percentage of abnormal segments at peak stress, and an abnormal left ventricular
      end-systolic volume response to stress were independent predictors of cardiac
      events. The model that best predicted subsequent cardiac events included clinical
      and stress echocardiographic data. CONCLUSIONS: Dobutamine stress
      echocardiography with semiquantitative segmental wall scoring provides important
      incremental information in predicting subsequent cardiac events.

PMID- 9576429
TI  - Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression,
      and fibrinogen binding in vitro and in vivo.
AB  - BACKGROUND: Recent data suggest that inhaled NO can inhibit platelet aggregation.
      This study investigates whether inhaled NO affects the expression level and
      avidity of platelet membrane receptors that mediate platelet adhesion and
      aggregation. METHODS AND RESULTS: In 30 healthy volunteers, platelet-rich plasma
      was incubated with an air/5% CO2 mixture containing 0, 100, 450, and 884 ppm
      inhaled NO. ADP- and collagen-induced platelet aggregation, the membrane
      expression of P-selectin, and the binding of fibrinogen to the platelet
      glycoprotein (GP) IIb/IIIa receptor were determined before (t0) and during the
      240 minutes of incubation. In addition, eight patients suffering from severe
      adult respiratory distress syndrome (ARDS) were investigated before and 120
      minutes after the beginning of administration of 10 ppm inhaled NO. In vitro, NO
      led to a dose-dependent inhibition of both ADP-induced (3+/-3% at 884 ppm versus
      70+/-6% at 0 ppm after 240 minutes; P<.001) and collagen-induced (13+/-5% versus
      62+/-5%; P<.01) platelet aggregation. Furthermore, P-selectin expression (36+/-7%
      of t0 value; P<.01) and fibrinogen binding (33+/-11%; P<.01) were inhibited. In
      patients with ARDS, after two who did not respond to NO inhalation with an
      improvement in oxygenation had been excluded, an increase in plasma cGMP,
      prolongation of in vitro bleeding time, and inhibition of platelet aggregation
      and P-selectin expression were observed, and fibrinogen binding was also
      inhibited (19+/-7% versus 30+/-8%; P<.05). CONCLUSIONS: NO-dependent inhibition
      of platelet aggregation may be caused by a decrease in fibrinogen binding to the
      platelet GP IIb/IIIa receptor.

PMID- 9576430
TI  - Decompensation of pressure-overload hypertrophy in G alpha q-overexpressing mice.
AB  - BACKGROUND: Receptor-mediated activation of myocardial Gq signaling is postulated
      as a biochemical mechanism transducing pressure-overload hypertrophy. The
      specific effects of Gq activation on the functional and morphological adaptations
      to pressure overload are not known. METHODS AND RESULTS: To determine the effects
      of intrinsic myocyte G alpha q signaling on the left ventricular hypertrophic
      response to experimental pressure overload, transgenic mice overexpressing G
      alpha q specifically in the heart (G alpha q-25) and nontransgenic siblings
      underwent microsurgical creation of transverse aortic coarctation and the
      morphometric, functional, and molecular characteristics of these pressure
      overloaded hearts were compared at increasing times after surgery. Before aortic
      banding, isolated G alpha q-25 ventricular myocytes exhibited contractile
      depression (depressed +dl/dt and -dl/dt) and G alpha q-25 hearts showed a pattern
      of fetal gene expression similar to the known characteristics of nontransgenic
      pressure-overloaded mice. Three weeks after transverse aortic banding, G alpha q
      25 left ventricles hypertrophied to a similar extent (approximately 30% increase)
      as nontransgenic mice. However, whereas nontransgenic mice exhibited concentric
      left ventricular remodeling with maintained ejection performance (compensated
      hypertrophy), G alpha q-25 left ventricles developed eccentric hypertrophy and
      ejection performance deteriorated, ultimately resulting in left heart failure
      (decompensated hypertrophy). The signature hypertrophy-associated progress of
      fetal cardiac gene expression observed at baseline in G alpha q-25 developed
      after aortic banding of nontransgenic mice but did not significantly change in
      aortic-banded G alpha q-25 mice. CONCLUSIONS: Intrinsic cardiac myocyte G alpha q
      activation stimulates fetal gene expression and depresses cardiac myocyte
      contractility. Superimposition of the hemodynamic stress of pressure overload on
      G alpha q overexpression stimulates a maladaptive form of eccentric hypertrophy
      that leads to rapid functional decompensation. Therefore G alpha q-stimulated
      cardiac hypertrophy is functionally deleterious and compromises the ability of
      the heart to adapt to increased mechanical load. This finding supports a
      reevaluation of accepted concepts regarding the mechanisms for compensation and
      decompensation in pressure-overload hypertrophy.

PMID- 9576431
TI  - Electrocardiographic imaging: Noninvasive characterization of intramural
      myocardial activation from inverse-reconstructed epicardial potentials and
      electrograms.
AB  - BACKGROUND: A recent study demonstrated the ability of electrocardiographic
      imaging (ECGI) to reconstruct, noninvasively, epicardial potentials,
      electrograms, and activation sequences (isochrones) generated by epicardial
      activation. The current study expands the earlier work to the three-dimensional
      myocardium and investigates the ability of ECGI to characterize intramural
      myocardial activation noninvasively and to relate it to the underlying fiber
      structure of the myocardium. This objective is motivated by the fact that cardiac
      excitation and arrhythmogenesis involve the three-dimensional ventricular wall
      and its anisotropic structure. METHODS AND RESULTS: Intramural activation was
      initiated by pacing a dog heart in a human torso tank. Body surface potentials
      (384 electrodes) were used to compute epicardial potentials noninvasively.
      Accuracy of reconstructed epicardial potentials was evaluated by direct
      comparison to measured ones (134 electrodes). Protocols included pacing from five
      intramural depths. Epicardial potentials showed characteristic patterns (1) early
      in activation, central negative region with two flanking maxima aligned with the
      orientation of fibers at the depth of pacing; (2) counterclockwise rotation of
      positive potentials with time for epicardial pacing, clockwise rotation for
      subendocardial pacing, and dual rotation for midmyocardial pacing; and (3)
      central positive region for endocardial pacing. Noninvasively reconstructed
      potentials closely approximated these patterns. Reconstructed epicardial
      electrograms and epicardial breakthrough times closely resembled measured ones,
      demonstrating progressively later epicardial activation with deeper pacing.
      CONCLUSIONS: ECGI can noninvasively estimate the depth of intramyocardial
      electrophysiological events and provides information on the spread of excitation
      in the three-dimensional anisotropic myocardium on a beat-by-beat basis.

PMID- 9576432
TI  - Effects of total replacement of atrial myosin light chain-2 with the ventricular
      isoform in atrial myocytes of transgenic mice.
AB  - BACKGROUND: In contrast to their well-known and critical role in excitation
      contraction coupling of vascular smooth muscle, the effects of the myosin light
      chains on cardiomyocyte mechanics are poorly understood. Accordingly, we designed
      the present experiment to define the cardiac chamber-specific functional effects
      of the ventricular isoform of the regulatory myosin light chain (MLC2v). METHODS
      AND RESULTS: Postnatal transgenic cardiac-specific overexpression of MLC2v was
      achieved by use of the alpha-myosin heavy chain promoter. Enzymatically
      disaggregated atrial and ventricular mouse myocytes were field-stimulated at
      multiple frequencies, and mechanical properties and calcium kinetics were studied
      by use of video edge detection and FURA 2-AM, respectively. MLC2v overexpression
      resulted in complete replacement of the atrial with the ventricular isoform of
      the regulatory myosin light chain at the steady-state mRNA and protein levels in
      the atria of transgenic mice. Mechanical properties of transgenic atrial myocytes
      were enhanced to the level of ventricular myocytes of control animals in
      association with modest decreases in the amplitude of the calcium transient.
      CONCLUSIONS: MLC2v modulates chamber-specific contractility by enhanced calcium
      sensitivity and/or improved cross-bridge cycling of the thin and thick filaments
      of the cardiomyocyte.

PMID- 9576433
TI  - Interpretation of outcomes of antiarrhythmic clinical trials: design features and
      population impact.

PMID- 9576434
TI  - Images in cardiovascular medicine. Cholesterol embolization: unrecognized
      complication of thrombolysis.

PMID- 9576435
TI  - Images in cardiovascular medicine. Intrapericardial teratoma.

PMID- 9576436
TI  - The Working Group report on Science-Based Categories for Abstracts: submitted to
      the annual Scientific Sessions. The Committee on Scientific Sessions Program
      (CSSP), American Heart Association.

PMID- 9576437
TI  - Gallstone pancreatitis, associated cholangitis, clinical predictors of persistent
      common duct stones, and ERCP or endoscopic sphincterotomy.

PMID- 9576438
TI  - Endoscopic management of esophagorespiratory fistulas: expanding our options with
      expandable stents.

PMID- 9576439
TI  - Renal and urologic complications of inflammatory bowel disease.
AB  - Renal and urologic complications are not uncommon in patients with inflammatory
      bowel disease, and can be directly or indirectly related to the underlying
      disease process or its treatment. Many of these patients have asymptomatic
      disease, or the urinary symptoms are nonspecific or overshadowed by bowel
      symptoms. By the time a urinary complication is considered, significant disease
      progression or renal damage may have occurred. These risks necessitate a high
      degree of diligence and periodic urologic evaluation as part of the long-term
      management of patients with inflammatory bowel disease.

PMID- 9576440
TI  - Primary sclerosing cholangitis: a clinical review.
AB  - Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized
      by fibro-obliterative inflammation of the entire biliary tree. It is a slowly
      progressive disease with an undulating course, resulting in terminal biliary
      cirrhosis after a median period of about 12 years after diagnosis. The etiology
      of the disease is unknown and there is no effective therapy that can halt disease
      progression. Around 8% of PSC patients develop cholangiocarcinoma, which, by the
      time it is diagnosed, cannot be treated curatively. The purpose of this article
      is to review the current knowledge about primary sclerosing cholangitis and to
      speculate on future strategies to address the issues of etiology and therapy.

PMID- 9576441
TI  - Microscopic colitis--no longer an appropriate term?

PMID- 9576442
TI  - Gallstone pancreatitis: a prospective study on the incidence of cholangitis and
      clinical predictors of retained common bile duct stones.
AB  - OBJECTIVE: The aim of this study was to define the incidence of cholangitis in
      gallstone pancreatitis, in the absence of cholangitis, to identify the clinical
      predictors of persistent common bile duct (CBD) stones at endoscopic retrograde
      cholangiography (ERCP) or at intraoperative cholangiography (IOC). METHODS: A
      total of 122 consecutive patients with acute gallstone pancreatitis were
      prospectively evaluated for the presence of CBD stones as determined by elective
      ERCP or IOC. Urgent ERCP was restricted to patients with concomitant cholangitis.
      APACHE II scores and serial laboratory data were obtained. RESULTS: Four (3%)
      patients had cholangitis and all underwent urgent ERCP successfully. Eighteen
      (15%) patients without cholangiogram were excluded. The remaining 100 patients
      underwent elective ERCP or IOC on a mean of hospital day 6.8. Twenty-one (21%)
      patients had persistent CBD stones. Univariate analysis detected significant
      differences in serum total bilirubin, ALT, and alkaline phosphatase levels
      between patients with and without persistent CBD stones. On multivariate
      analysis, serum total bilirubin on hospital day 2 was the best predictor of CBD
      stones. A serum total bilirubin level > 1.35 mg/dl had a sensitivity of 90.5% and
      specificity of 63%. Age, gender, mean APACHE II score, amylase, and presence of
      CBD dilation on ultrasound were not predictive of CBD stones. CONCLUSION: In
      patients with gallstone pancreatitis, 1) cholangitis is uncommon, and 2) the best
      clinical predictor of persistent CBD stones is serum total bilirubin on hospital
      day 2.

PMID- 9576443
TI  - Palliative treatment of malignant esophagorespiratory fistulas with Gianturco-Z
      stents. A prospective clinical trial and review of the literature on covered
      metal stents.
AB  - OBJECTIVE: Esophagorespiratory fistulas, especially in the upper third of the
      esophagus, are a complication of malignant esophageal tumors, which are difficult
      to manage. The efficacy of polyurethane-covered, self-expanding metal stents for
      palliation of malignant esophagorespiratory fistulas was investigated
      prospectively. METHODS: Eleven patients with malignant esophagorespiratory
      fistulas resp. perforations were treated with Gianturco-Z stents. In five
      patients the lesion was located in the proximal part of the esophagus. Because of
      the fistula all patients suffered from dysphagia even for liquids. RESULTS: No
      technical problems during the implantation procedure of the stents occurred. In
      the control radiography with water-soluble contrast media, the fistulas were
      completely sealed in 10 of 11 patients. Therefore the dysphagia score improved
      from 3.0 to 0.6. Nearly all Gianturco-Z stents (10/11) showed a sufficient
      expansion within 24 h after placement. Severe early or late complications were
      not encountered, with the exception of tumor overgrowth in one patient about 9
      months after stent placement. In five patients, short term (3-6 days)
      retrosternal pain was observed, and one patient complained of slight foreign body
      sensation. By August 1997 all 11 patients had died of advanced disease, with a
      median survival time of 121 days (range, 22-300 days). CONCLUSIONS: Gianturco-Z
      stents are highly effective for palliative treatment of esophagorespiratory
      fistula resp. perforations and have a low complication rate. Due to the fact that
      this stent shows no retraction during the release, a precise positioning is
      possible, especially in the case of tumors and fistulas in the upper third of the
      esophagus. It seems that use of the Gianturco-Z stent can be considered a good
      therapeutic method for palliative endoscopic treatment of this high risk patient
      group.

PMID- 9576444
TI  - The development of dysplasia and adenocarcinoma during endoscopic surveillance of
      Barrett's esophagus.
AB  - OBJECTIVE: Periodic endoscopic surveillance is generally recommended for patients
      with Barrett's esophagus. The optimal follow-up strategy for uncomplicated
      Barrett's esophagus is controversial, in part because of limited data on the rate
      of neoplastic progression (through the sequence of metaplasia-dysplasia
      carcinoma) during endoscopic surveillance. This study aims to quantify the
      development of dysplasia in patients with uncomplicated Barrett's esophagus and
      to explore clinical risk factors associated with the development of dysplastic
      lesions. METHODS: We identified 102 patients with endoscopic evidence of
      Barrett's esophagus and the presence of specialized columnar epithelium who had
      received endoscopic surveillance for adenocarcinoma at our medical center between
      1970 and 1994. We abstracted endoscopic and histologic data from the medical
      record. All specimens that showed any degree of atypia (per report) were
      reexamined in blinded fashion by a team of study pathologists who indicated the
      grade of dysplasia. Time to first diagnosis of dysplasia was plotted using Kaplan
      Meier survival curves, and risk factors for development of dysplasia were
      assessed using Cox regression. RESULTS: During 563 patient-yr of endoscopic
      follow-up, three patients developed adenocarcinoma at least 4 yr after initial
      diagnosis (one developed adenocarcinoma of the cardia, which was incidentally
      detected during surveillance for Barrett's esophagus). At some point during
      follow-up, 19 patients developed new onset, low grade dysplasia and four
      developed high grade dysplasia. None of the patients who had received antireflux
      surgery developed dysplasia. CONCLUSION: If confirmed by larger follow-up
      studies, our results suggest that surveillance endoscopy can be safely deferred
      for at least 2 yr following an initial biopsy that is negative or indeterminate
      for dysplasia. Adoption of this approach would substantially reduce the cost of
      surveillance for adenocarcinoma. Future trials should explore the role of
      antireflux surgery in protecting against neoplastic transformation of Barrett's
      esophagus.

PMID- 9576445
TI  - Barrett's esophagus and the presence of Helicobacter pylori.
AB  - OBJECTIVE: Although the role of Helicobacter pylori in the pathogenesis of peptic
      ulcer disease and antral gastritis has been well documented, the role of H.
      pylori in esophageal disease has not been clearly defined. To clarify this issue,
      we analyzed 141 patients with histologically confirmed esophageal disease.
      METHODS: The study group consisted of 82 patients with Barrett's esophagus, 19
      with adenocarcinoma of the esophagus arising in columnar epithelium and 40
      patients with reflux esophagitis without columnar metaplasia of the esophagus. In
      each of these cases the presence or absence of H. pylori was assessed
      histologically. RESULTS: H. pylori was present in 19 of 82 patients (23%) with
      Barrett's esophagus, but was absent in all patients with adenocarcinoma of the
      esophagus and in patients with reflux esophagitis without Barrett's metaplasia.
      H. pylori was found only in areas of gastric type metaplasia in the patients with
      Barrett's esophagus. All of the 19 Barrett's esophagus group with H. pylori had
      chronic inflammation, and in 16 the inflammation was severe. H. pylori was
      significantly associated with severity of inflammation in patients with Barrett's
      esophagus (p < 0.001). Members of the Barrett's group with evidence of moderate
      to severe dysplasia were negative for H. pylori. CONCLUSION: These data confirm
      that the presence of gastric type mucosa within the esophagus is a prerequisite
      for H. pylori colonization, and that H. pylori may contribute to the severity of
      inflammation in Barrett's epithelium.

PMID- 9576446
TI  - Cisapride 20 mg b.i.d. provides symptomatic relief of heartburn and related
      symptoms of chronic mild to moderate gastroesophageal reflux disease. CIS-USA-52
      Investigator Group.
AB  - OBJECTIVE: We evaluated the efficacy and safety of a twice-daily dosage regimen
      of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal
      reflux disease (GERD) in patients with moderate intensity heartburn and no
      history of erosive esophagitis. METHODS: After a 2-wk, single-blind, placebo run
      in period, 398 patients who continued to experience moderate intensity heartburn
      were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice
      daily for 4 wk. RESULTS: Compared with placebo, cisapride significantly reduced
      scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p <
      0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg
      b.i.d. was also superior to placebo in reducing total use of rescue antacid
      medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime
      heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn
      free days and antacid-free nights (p < 0.5); and increasing the percentage of
      patients self-rated as having minimal or better symptomatic improvement (p =
      0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event
      in the cisapride group was diarrhea, reported by 10% of patients, compared with
      an incidence of 4% in the placebo group. CONCLUSION: Cisapride 20 mg b.i.d. was
      shown to be effective and safe for the short-term treatment of daytime and
      nighttime heartburn and for other symptoms associated with mild-moderate GERD.

PMID- 9576447
TI  - How do clinicians practicing in the U.S. manage Helicobacter pylori-related
      gastrointestinal diseases? A comparison of primary care and specialist
      physicians.
AB  - OBJECTIVES: We sought to examine the extent to which physicians recognize H.
      pylori as a causal agent in peptic ulcer disease or as a potential cofactor in
      other gastrointestinal diseases, and to observe how this knowledge has influenced
      diagnostic and therapeutic practices. METHODS: We used a national mail survey in
      the U.S. between February and May of 1996, querying 5994 U.S. physicians
      (family/general practitioners [FPs], internists [IMs], and gastroenterologists)
      selected at random from three different membership databases of professional
      associations. RESULTS: The response rate was 52%. More than 95% of physicians who
      treat symptoms empirically would prescribe acid suppressant therapy rather than
      anti-H. pylori therapy. Between 43% and 66% of physicians, varying in frequency
      by medical specialty, would treat the infection in H. pylori-positive patients
      with nonulcer dyspepsia. In confirmed peptic ulcer disease, between 88% and 100%
      of physicians would treat the H. pylori infection, depending on the physician
      group and whether or not the presentation of an ulcer was recurrent. Although 103
      distinct anti-H. pylori regimens were reported, 89% of the gastroenterologists
      and 70% of the primary care physicians (PCPs) used combinations of antimicrobials
      with reported cure rates of at least 80%. CONCLUSIONS: General knowledge
      regarding H. pylori-associated diseases was widespread among primary care
      physicians and gastroenterologists. However, anti-H. pylori therapies judged
      ineffective were reported as the first choice regimen by 5% of
      gastroenterologists and 18% of primary care physicians. Gastroenterologists
      appear to implement the latest scientific developments in the field rapidly
      whereas PCPs manifest a delayed response, due to either insufficient knowledge or
      to other factors influencing their approach to treatment.

PMID- 9576448
TI  - Cost-effectiveness of noninvasive testing and treatment strategies for H. pylori
      infection in children with dyspepsia.
AB  - OBJECTIVE: We sought to model the cost-effectiveness of endoscopy, noninvasive
      testing and treatment strategies for Helicobacter pylori infection in children
      with recurrent abdominal pain in two health care systems, those of the United
      States and Finland. METHODS: Initial serological testing and treatment was
      compared to empirical treatment with antimicrobials, endoscopy with rapid urease
      testing, and 13C urea breath testing. Key assumptions and ranges were obtained
      from the published literature. Costs were determined for the acquisition of
      various tests and actual reimbursement figures were used for procedural costs.
      RESULTS: The disease management costs were very similar for both endoscopy
      ($643.00) and serology ($646.00) in the United States. In Finland, endoscopy
      ($173.00) was less expensive than serology ($192.00). The 13C urea breath test
      was the most expensive procedure in the United States. Sensitivity analysis
      demonstrated that serological testing became the preferred path if its cost was <
      $42 in the United States. Empirical treatment of children with dyspepsia was not
      cost-effective in either country. Sensitivity analysis showed that when
      prevalence of infection was > 53% in children with recurrent abdominal pain,
      empirical therapy with endoscopy reserved for failures was the optimal path.
      CONCLUSIONS: In developed countries like the United States and Finland,
      significant cost savings are unlikely with an initial test and treat strategy
      based on serology. Noninvasive testing and treatment of H. pylori infection can
      be cost-effective in populations with highly prevalent rates of infection.

PMID- 9576449
TI  - Biopsy sites suitable for the diagnosis of Helicobacter pylori infection and the
      assessment of the extent of atrophic gastritis.
AB  - OBJECTIVES: We performed this study to determine which biopsy sites in the
      stomach are suitable for the diagnosis of Helicobacter pylori infection and the
      assessment of the extent of atrophic gastritis. METHODS: Endoscopy was performed
      in 76 H. pylori-positive patients with histologically confirmed chronic
      gastritis. Biopsies were taken from the following six sites: the lesser
      curvatures of the mid-antrum (site 1), the angulus (site 2), the middle body
      (site 3), and the greater curvatures of the mid-antrum (site 4), the angulus
      (site 5), and the middle body (site 6) of the stomach. The extent of atrophic
      gastritis was assessed endoscopically as well as histologically, and patients
      were classified into five groups according to its extent. H. pylori status was
      assessed histologically. The histological severity of inflammation, activity,
      atrophy, and intestinal metaplasia was assessed according to the Updated Sydney
      System. The grades of these items were compared among the six biopsy sites in
      each group of patients. RESULTS: Site 6 was most reliable for the diagnosis of H.
      pylori infection, and site 4 was suitable for examining the status of H. pylori
      colonization in the antrum. Site 1, site 3, and site 6 were suitable for the
      assessment of the extent of atrophic gastritis. CONCLUSIONS: Our results indicate
      that for an accurate diagnosis and assessment, biopsies should be taken from the
      following four sites: the lesser curvatures of the mid-antrum (site 1) and middle
      body (site 3), and the greater curvatures of the mid-antrum (site 4) and middle
      body (site 6) of the stomach.

PMID- 9576450
TI  - Prevalence of Helicobacter pylori in peptic ulcer patients in greater Rochester,
      NY: is empirical triple therapy justified?
AB  - OBJECTIVES: Among patients with peptic ulcer disease, the prevalence of
      Helicobacter pylori has been reported to range from 80% to 90%. Thus empirical
      cost-effective therapy has been suggested. We surveyed patients with peptic ulcer
      disease in Rochester, NY. METHODS: From two teaching hospitals all patients who
      had duodenal ulcers (DU) and/or gastric ulcers (GU) on esophagogastroduodenoscopy
      (EGD) with antral biopsy for histology for H. pylori and for rapid urease (CLO)
      test were included in the study. We examined a total of 160 patients with DU and
      145 patients with GU, age range 18-92 yr, obtaining clinical data, race,
      medication profile, and history of use of nonsteroidal antiinflammatory drugs
      (NSAIDs). An ulcer was defined if the lesion with loss of mucosal integrity was >
      or = 0.5 cm, with apparent depth. H. pylori was considered present if CLO test
      and/or histology were positive for H. pylori. To confirm the reliability of
      nonuse of NSAIDs, we randomly checked blood samples of 90 such patients from the
      ambulatory clinic for the presence of salicylates. To identify the sensitivity of
      the CLO test, we performed a serology test for H. pylori antibody in 100 subjects
      to compare the CLO test results. Also, 500 CLO test results were compared to the
      histology results for H. pylori. RESULTS: Among 160 DU patients, 16 were NSAID
      users with negative H. pylori and excluded from the prevalence study. Of the
      remaining 144 patients with DU, H. pylori was present in 88 patients (61%). When
      these data were analyzed according to race, H. pylori was present in 54 (52%) of
      104 whites compared to 34 of 40 (85%) nonwhites (blacks, Hispanics, Asians) (p <
      0.01). Among 145 GU patients 18 were NSAID users with negative H. pylori and
      excluded from the prevalence analysis. Of the remaining 127 patients with GU, H.
      pylori was present in 87 patients (61%). Among them, H. pylori was present in 46
      of 87 (53%) whites, whereas 31 of 40 nonwhites (78%) were H. pylori-positive (p <
      0.01). Antral histology and CLO test for H. pylori were in agreement in 92% of
      cases. Serology and CLO test for H. pylori were in agreement in 87% of cases.
      None of the randomly screened patients, including 16 ulcer patients with negative
      H. pylori, showed presence of salicylate in blood. CONCLUSION: In greater
      Rochester, NY, where the majority of our patients with EGD were whites, the
      prevalence of H. pylori among ulcer patients was lower compared to other regions,
      particularly among whites. This suggests that an additional causative factor or
      factors for peptic ulcers may be present. Hence, empirical antibiotic therapy of
      ulcer patients without confirming the presence of H. pylori may not be justified.

PMID- 9576451
TI  - An increased number of follicles containing activated CD69+ helper T cells and
      proliferating CD71+ B cells are found in H. pylori-infected gastric mucosa.
AB  - OBJECTIVE: An immune response occurring in Helicobacter pylori-infected gastric
      mucosa could have a direct implication for associated pathologies. In the present
      study we analyzed the expression of the immune activation, proliferation, and
      phenotype markers by immune cell subpopulations in H. pylori-infected and
      uninfected gastric samples. METHODS: Antral gastric biopsies from both H. pylori
      positive and -negative patients were processed by immunohistochemistry; gastric
      epithelial cells were isolated from biopsy tissue and analyzed by flow cytometry.
      RESULTS: Ten of the 13 biopsies that contained follicles were H. pylori positive.
      Follicular CD69 was expressed mainly by CD4+ T cells and the central core of
      follicles showed double immunopositivity for the B-cell marker CD19 and
      transferrin receptor. Also detected was an increase in the percentage of
      epithelial cells from H. pylori-positive samples expressing HLA-DR and beta2
      microglobulin, compared to negative samples (61 +/- 15% vs 9 +/- 9%, p = 0.003
      and 93 +/- 7% vs 52 +/- 18%, p = 0.002, respectively), whereas no variation on
      class I HLA was detected. CONCLUSIONS: These results suggest that chronic H.
      pylori infection could facilitate the persistence of follicles on which
      continuous follicular helper T-cell activation could lead to uncontrolled
      follicular B-cell proliferation. Furthermore, beta2 microglobulin expression by
      epithelial cells in a nonparallel way to class I HLA may indicate the possibility
      of nonclassical class I MHC expression on the basal surface of the epithelium.

PMID- 9576453
TI  - Hepatitis C infection risk analysis: who should be screened? Comparison of
      multiple screening strategies based on the National Hepatitis Surveillance
      Program.
AB  - OBJECTIVES: Hepatitis C, an infection of high prevalence worldwide, is
      insidiously progressive in many. Reduction of person-to-person spread is
      possible, and treatment is possible for many, particularly if offered before
      cirrhosis develops. Screening for hepatitis C (HCV) would be appropriate if
      strategies could be developed to afford adequate sensitivity and specificity at
      reasonable cost. We evaluated the performance characteristics of several
      screening strategies to determine the best balance between cost and performance.
      METHODS: The database of a national hepatitis screening program was used to
      define risk factors for HCV. Features associated with increased risk for HCV by
      multivariable analysis were combined in various ways to construct HCV screening
      models. Screening Model 1 employed a mathematical model constructed to predict
      the probability of hepatitis C. Using this model, testing for HCV was done if the
      probability of HCV was determined to be higher than 7%. Models 2 and 3 called for
      HCV testing if certain risk factors, stratified as socially intrusive, or
      nonintrusive in nature, were present. Model 4 calls for testing for HCV only when
      ALT values are elevated. Costs per case discovered were calculated for each
      model. RESULTS: Nine thousand two-hundred sixty-nine individuals from a database
      of 13,997 has sufficient information to be included in the modeling studies. Risk
      factors considered socially intrusive were intravenous (i.v.) drug use and sex
      with an i.v. drug user. Risk factors considered not socially intrusive were:
      history of blood transfusion, age 30-49 yrs, and male gender. The sensitivity of
      Models 1-4 were 65%, 69%, 53%, and 63%, respectively. Specificities were 84%,
      74%, 77%, and 92%, respectively. The cost per case detected was lowest when
      Models 1 or 2 were used ($357 and $439, respectively) and higher for models 3 and
      4 ($487 and $1047, respectively). CONCLUSIONS: The yield and cost of screening
      for HCV compares favorably with accepted current screening practices for other
      diseases. Models 1, 2, and 3 may be appropriate in certain clinical and
      epidemiological settings. Selective screening by a risk factor questionnaire
      (first three models) is more cost-effective than blood testing with ALT (Model
      4).

PMID- 9576452
TI  - Triple versus dual therapy for eradicating Helicobacter pylori and preventing
      ulcer recurrence: a randomized, double-blind, multicenter study of lansoprazole,
      clarithromycin, and/or amoxicillin in different dosing regimens.
AB  - OBJECTIVE: The efficacy and safety of dual and triple therapies with a proton
      pump inhibitor and antibiotic(s) for therapy of Helicobacter pylori-associated
      duodenal ulcer disease have been compared using results from independent studies
      using different methods and regimens, making interpretation difficult. In a
      large, double-blind, multicenter study conducted in the United States, we
      compared a triple therapy regimen with four dual therapy and one monotherapy
      regimens in the eradication of H. pylori and the prevention of ulcer recurrence.
      METHODS: Patients with active duodenal ulcer disease or history of duodenal ulcer
      disease within the past year and H. pylori infection were randomized to receive
      one of six 14-day treatment regimens: lansoprazole 30 mg, clarithromycin 500 mg,
      and amoxicillin 1 gm b.i.d.; lansoprazole 30 mg b.id. and either clarithromycin
      500 mg b.i.d. or t.i.d.; lansoprazole 30 mg b.i.d. or t.i.d. with amoxicillin 1
      gm t.i.d.; or lansoprazole 30 mg t.i.d. alone. No additional acid suppression
      therapy followed eradication therapy. Primary efficacy endpoints were eradication
      of H. pylori and ulcer recurrence. RESULTS: Of 396 patients enrolled in the
      study, 352 met the entry criteria for duodenal ulcer status and H. pylori
      positivity. At 4-6 wk after the end of therapy, H. pylori was eradicated from 94%
      (44 of 47) of patients receiving lansoprazole, clarithromycin, and amoxicillin
      triple therapy, 77% (39 of 51) of those receiving lansoprazole t.i.d./amoxicillin
      t.i.d., 75% (36 of 48) of those receiving lansoprazole b.i.d./clarithromycin
      t.i.d., 57% (28 of 49) of those receiving lansoprazole b.i.d./clarithromycin
      b.i.d., 53% (26 of 49) of those receiving lansoprazole b.i.d./amoxicillin t.i.d.,
      and 2% (1 of 53) of those receiving lansoprazole monotherapy (p < or = 0.05,
      triple therapy vs each dual therapy and each dual therapy vs monotherapy). Of
      those patients who were documented as free of ulcer at 4-6 wk after treatment,
      ulcers recurred within 6 months in 7% of patients receiving triple therapy, as
      compared with 13-23% of patients receiving dual therapy, and 69% of patients
      receiving lansoprazole monotherapy. Patients who were H. pylori negative at 4-6
      wk after treatment were less likely to have an ulcer recurrence than were
      patients who were H. pylori positive (11% [10 of 95] vs 47% [20 of 43],
      respectively, across treatment groups). For triple therapy and dual therapy, a
      similar proportion of patients reported a drug-related adverse event (23% vs 17
      33%, respectively). CONCLUSIONS: In patients with active or a recent history of
      duodenal ulcer, a 14-day course of lansoprazole-based triple therapy without
      additional acid suppression therapy is highly effective in the eradication of H.
      pylori and in preventing ulcer recurrence. Among the dual therapies, higher
      eradication rates occurred when lansoprazole (with amoxicillin) or clarithromycin
      (with lansoprazole) was administered t.i.d. vs b.i.d., but the rates were still
      significantly lower than with lansoprazole triple therapy with all three drugs
      administered b.i.d.

PMID- 9576454
TI  - Risk factors associated with chronic hepatitis C virus infection: limited
      frequency of an unidentified source of transmission.
AB  - OBJECTIVES: Risk factors have been studied in patients with acute non-A, non-B
      hepatitis, and approximately 40-50% have no known risk factor for viral
      acquisition. A significant undefined source of viral transmission has been
      suggested. We sought to clearly delineate the risk factors in a population of
      patients with documented chronic hepatitis C virus (HCV) infection to assess the
      magnitude of HCV transmission without known risk factors. METHODS: Risk factor
      profiles were carefully assessed in 301 consecutive patients with chronic HCV
      infection. Patients were classified by gender and age. Overall risk factor
      distributions were calculated and comparisons were made between groups to detect
      differences in mode of HCV acquisition. RESULTS: One hundred ninety-six men and
      105 women were studied; 223 were age < or = 45 yr and 78 were > 45 yr. Overall,
      25% of patients had a history of transfusion and 49% had a history of intravenous
      drug use (i.v.DU). Only 12% had no history of risk factor exposure. Men were more
      likely to have a history of i.v.DU and less likely to have a history of blood
      transfusion or sexual exposure/household contact. Younger patients were more
      likely to have a history of i.v.DU and older patients were more likely to have a
      history of blood transfusion and to deny all risk factor exposure. CONCLUSIONS: A
      careful history delineated a potential risk factor for HCV acquisition in 88% of
      patients with chronic HCV infection. Men and younger patients had different risk
      factor profiles than women and older patients, respectively. It is likely that an
      important unknown mode of HCV transmission occurs in a significant minority of
      patients.

PMID- 9576455
TI  - The changes in quantitative HCV RNA titers during interferon alpha 2B therapy in
      patients with chronic hepatitis C infection.
AB  - OBJECTIVE: Our aim was to analyze the outcomes and the patterns of response to
      interferon treatment in patients with chronic hepatitis C using serum HCV RNA as
      the primary endpoint of therapy. METHODS: Seventy anti-HCV-positive patients were
      treated with 3 million U of interferon-alpha-2b thrice weekly for 24 wk and
      followed for an additional 24 wk after cessation of therapy (wk 48). Serum HCV
      RNA was measured by a reverse transcriptase-polymerase chain reaction method that
      has a sensitivity of < 100 viral copies per ml. RESULTS: The mean pretreatment
      HCV RNA was 2.8 +/- 2.2 x 10(6) viral copies per ml. Genotype 1 patients had
      significantly higher mean baseline viral titers than those with genotype 2 (p =
      0.03). At wk 48, 12 (17%) patients were HCV RNA negative and considered
      virological complete responders (CR) to treatment. The remaining patients were
      HCV RNA positive at wk 48 and were considered nonresponders to therapy. There
      were two types of virological nonresponder patients, responder relapse (RR) and
      no response (NR). The mean baseline HCV RNA level was significantly lower in the
      virological CR patients (p = 0.0004). At wk 12 and 24 of interferon treatment,
      both the virological CR and RR patients had lower serum HCV RNA concentrations
      than the patients in the NR category (p = 0.0001), while at wk 48, only. the
      virological CR patients had undetectable HCV RNA when compared to the RR and NR
      patients (p = 0.04). Transient decreases in the HCV RNA titers of > or = 1 log in
      magnitude were observed in 49% of the NR patients, which rose to pretreatment
      levels either during or after interferon therapy. CONCLUSIONS: Our findings
      indicate that measurement of serum HCV RNA precisely defined the responses to
      interferon therapy. Because the goal is to eliminate virus in patients with
      chronic hepatitis C infection, then HCV RNA should be used as the primary
      endpoint of treatment.

PMID- 9576456
TI  - Intestinal tuberculosis: clinicopathologic analysis and diagnosis by endoscopic
      biopsy.
AB  - OBJECTIVES: Tuberculosis is still an important cause of granulomatous colitis in
      developing countries. If we can diagnose tuberculosis using endoscopic biopsy
      material, clinicians can avoid invasive diagnostic procedures and needless
      operations. For this purpose, we evaluated clinical manifestations, pathological
      findings, and diagnostic methods in endoscopically biopsied intestinal
      tuberculosis patients. METHODS: From January 1991 to December 1996, 42 patients
      with intestinal tuberculosis were endoscopically examined and tissue culture,
      immunohistochemical stain, Ziehl-Neelsen stain, and polymerase chain reaction in
      fresh and fixed tissue were applied. The pathological findings were analyzed and
      compared with the results of the other diagnostic methods. RESULTS: In
      tuberculosis patients, transverse ulcers with surrounding hypertrophic mucosa and
      multiple erosions were usual colonoscopic findings. The granulomas were found in
      74% of the cases. The positivity ranged from 30-45%. There were no significant
      differences in the positivity among those diagnostic methods (p > 0.05). The
      positivity of Ziehl-Neelsen stain in fixed tissue was higher in the group having
      granulomas and it was reversed in PCR (p < 0.05). The increasing number of biopsy
      particles raised the positivity of Ziehl-Neelsen stain and PCR in fixed tissue (p
      < 0.05). CONCLUSIONS: Transverse ulcers were the most characteristic colonoscopic
      finding and granulomas were frequent pathological findings in intestinal
      tuberculosis. Higher positivity and reliable results were found in tissue
      culture, Ziehl-Neelsen stain, and polymerase chain reaction. To increase the
      diagnostic rate, the endoscopist should take enough tissue and deep biopsy
      material from ulcer bases and diseased mucosae.

PMID- 9576457
TI  - Significance of diminished factor XIII in Crohn's disease.
AB  - OBJECTIVE: Coagulation factor XIII is a plasma transglutaminase involved in
      crosslinking of fibrin, the last step of the coagulation system and a connective
      tissue factor contributing to the wound healing process. It circulates as a
      heterotetrameric molecule consisting of two identical proenzyme subunits (factor
      XIIIA) and two carrier protein subunits (factor XIIIS). The aim of this study was
      to determine the disease features associated with the diminution of factor XIII
      in Crohn's disease. METHODS: Factor XIIIA and factor XIIIS levels were assessed
      in patients presenting with Crohn's disease, ulcerative colitis, infectious
      colitis, or diverticulitis, in patients with rheumatoid arthritis, and in control
      subjects. Prothrombin fragment 1 + 2 assay, as a marker of the generation of
      thrombin and measurement of C-terminal telopeptide of type I collagen as an
      estimate of degradation of collagen type I, were performed. RESULTS: Factor XIIIA
      was significantly decreased in Crohn's disease, in ulcerative colitis, and in
      infectious colitis by comparison with subjects presenting with diverticulitis,
      normal, and rheumatoid subjects p = 0.0001). Factor XIIIS was unmodified in
      patients with Crohn's disease by comparison with controls but was reduced in
      those presenting with intestinal bleeding (p = 0.0002). In Crohn's disease, the
      lowest level of factor XIIIA was observed in patients with intestinal bleeding (p
      = 0.0003). Factor XIIIA was correlated with the Van Hees index (r = -0.5661; p =
      0.0001) and with the C-terminal telopeptide of type I collagen (r = -0.4110; p =
      0.0011) but not with prothrombin fragment 1 + 2. The multiple regression analysis
      showed that only Van Hees index and intestinal bleeding were independent
      variables for explaining the diminution of Factor XIIIA in Crohn's disease.
      CONCLUSIONS: Factor XIIIA subunit is an indicator of Crohn's disease activity.
      Our study suggests that a low factor XIIIA level is related to the presence of
      intestinal lesions and might be linked to intestinal repair mechanisms; loss in
      intestinal lumen could be also involved, especially in patients with intestinal
      bleeding.

PMID- 9576458
TI  - Colonic polyps: experience of 236 Indian children.
AB  - OBJECTIVES: We studied the clinical spectrum, histology, and malignant potential
      of colonic polyps in Indian children (< or =12 yr). METHODS: Two hundred thirty
      six children with colonic polyps were studied from January 1991 to October 1996.
      They were evaluated clinically and colonoscopic polypectomy was done. Children
      with five or more juvenile polyps were labeled as having juvenile polyposis and
      serial colonoscopic polypectomies were done every 3 wk. Colectomy was performed
      when there were intractable symptoms or clearing of the polyps by colonoscopy was
      not possible. Histological examination of the polyps was done. Follow-up
      colonoscopy was done in children with juvenile polyposis only. RESULTS: The mean
      age of these children was 6.12 +/- 2.7 yr, with a male preponderance (3.5:1).
      Rectal bleeding of a mean duration of 14 +/- 16 months was the presenting symptom
      in 98.7%. Solitary polyps were seen in 76%, multiple polyps in 16.5%, and
      juvenile polyposis in 7% (n = 17) of the children. A majority (93%) of the polyps
      were juvenile and 85% were rectosigmoid in location. Adenomatous changes, seen in
      11%, were more common in juvenile polyposis (59%) than in juvenile polyps (5%).
      Among those with juvenile polyposis, colon clearance was achieved in eight, six
      required colectomy for intractable symptoms, and three were still on the
      polypectomy program. Polyps recurred in 5% of children with juvenile polyps and
      37.5% of those with juvenile polyposis. CONCLUSIONS: Juvenile polyps remain the
      most common colonic polyps in children. A significant number of cases of polyps
      are multiple and proximally located, which emphasizes the need for total
      colonoscopy in all. Juvenile polyps should be removed even if asymptomatic
      because of their neoplastic potential. Colonoscopic polypectomy is effective even
      in juvenile polyposis. Surveillance colonoscopy is required in juvenile polyposis
      only.

PMID- 9576459
TI  - Colonic chicken skin mucosa: an endoscopic and histological abnormality adjacent
      to colonic neoplasms.
AB  - OBJECTIVES: We recently described an endoscopic finding of pale yellow-speckled
      mucosa adjacent to colonic neoplasms. This resembled the appearance of chicken
      skin and was named chicken skin mucosa (CSM). CSM differs from previously
      reported gastrointestinal xanthelasmas in that this entity always occurs in
      association with colonic neoplasms. The prevalence, endoscopic characteristics,
      clinical significance, and possible etiology were investigated. METHODS: Eight
      hundred fifty-two consecutive colonoscopies were prospectively evaluated for the
      presence of CSM associated with either cancer or adenomas > or = 1 cm. Electron
      microscopy and histopathology using hemotoxylin and eosin, mucicarmine, and oil
      red O stains were performed. Twelve consecutive colon cancer resection specimens
      were prospectively examined to determine the presence of histologic CSM. RESULTS:
      CSM was adjacent to eight of 10 distal colorectal cancers, one of four proximal
      colon cancers, 16 of 42 distal adenomas, and three of 44 proximal adenomas. Four
      of seven resected distal cancers demonstrated histological evidence of CSM.
      Biopsies of the CSM revealed that lipid-filled macrophages in the lamina propria
      were responsible for this endoscopic appearance. Electron microscopy showed that
      the surface epithelial cells had small intestine-like microvilli. CSM was not
      seen with other colonic conditions and was not associated with the laxative
      preparation. In four instances, identification of the CSM alerted the endoscopist
      to the presence of polyps in locations difficult to visualize. CONCLUSIONS: CSM
      is an endoscopic entity that occurs as a result of fat accumulation in
      macrophages in the lamina propria of the mucosa adjacent to colonic neoplasms.
      Small intestine-like microvilli were present in CSM and the pathophysiological
      implications remain to be elucidated.

PMID- 9576460
TI  - Accelerated right colonic emptying after simulated upper gut hemorrhage.
AB  - OBJECTIVE: Upper gastrointestinal hemorrhage delays gastric emptying. Our aim was
      to evaluate the effect of gastrointestinal hemorrhage on small intestinal,
      ileocecal, and proximal colonic transit. METHODS: Healthy volunteers were
      randomized to receive either a duodenal infusion of heparinized autologous blood
      (n = 7) or egg white, acting as a control substance with similar composition; 1.5
      mCi99mTc-DTPA was added to the infused substances. We infused 30 ml at an
      infusion rate of 1 ml/min. Gamma-camera images were taken for 4 h or until all
      radioactivity had entered the colon. Arrival of radiolabels in the colon and also
      counts in the ascending and transverse colon were quantified. RESULTS: Small
      intestinal and ileocecal transit were not significantly different between blood
      and egg white infusions. However, ascending colonic emptying was significantly
      faster after blood infusion compared to egg white. Four hours after the start of
      blood infusion a median of 30% of counts were in the transverse colon (11-50%;
      25th-75th percentile) versus 0% (0-7%) after egg white infusion (p < 0.001).
      CONCLUSION: We concluded that simulated upper gastrointestinal bleeding hastens
      proximal colonic transit, but does not alter small intestinal transit and colonic
      filling.

PMID- 9576461
TI  - Contrast-enhanced endoscopic ultrasonography in pancreatic diseases: a
      preliminary study.
AB  - OBJECTIVE: The purpose of this study was to clarify the usefulness of contrast
      enhanced endoscopic ultrasonography in pancreatic diseases. METHODS: The subjects
      comprised 37 patients with pancreatic diseases: 11 with ductal cell carcinoma, 10
      with mucin-producing tumor, five with pseudo-cyst, four with islet cell tumor,
      four with chronic pancreatitis, and three with serous cystadenoma. After
      endoscopic ultrasonography, Albunex (0.22 ml/kg) was injected intravenously at a
      rate of 1 ml/s into the right median vein, and observation was continued for 10
      min. The presence or absence of enhancement of the lesion was determined in each
      disease. Because all the patients with ductal cell carcinoma, islet cell tumor,
      chronic pancreatitis, and serous cystadenoma, as well as five with mucin
      producing tumor and three with pseudo-cyst, underwent angiography, vascularity
      was compared between angiographic images and those of contrast-enhanced
      ultrasonography. RESULTS: Enhancement of the lesion was observed in all patients
      with islet cell tumor and serous cystadenoma, in eight with mucin-producing
      tumor, and in three with chronic pancreatitis. However, no enhancement effect was
      observed in the patients with ductal cell carcinoma and those with pseudo-cyst.
      Comparison between the images of contrast-enhanced endoscopic ultrasonography and
      angiographic images showed three patients in whom angiograms were hypovascular,
      but enhancement effect was observed on ultrasonographic images. CONCLUSION: The
      combined evaluation of plain and enhanced images of endoscopic ultrasonography
      may be useful for the diagnosis of pancreatic diseases.

PMID- 9576462
TI  - Enterococcal bacteremia after transjugular intrahepatic portosystemic shunts
      (TIPS).
AB  - The objective of this study was to analyze a series of patients with Enterococcus
      faecium infection following transjugular intrahepatic portosystemic shunts (TIPS)
      in order to define the risk factors, outcome, and role of treatment including
      hepatic transplantation. This study is a case series from a tertiary referral
      center for liver transplantation. The medical records of four patients referred
      to one teaching hospital in San Francisco between 1990 and 1995 for evaluation or
      management of Enterococcal infection following TIPS were reviewed. A review of
      the microbiology records of all 314 patients who underwent TIPS at that
      institution and a MEDLINE search were performed to assess whether any other cases
      existed. The effect of therapy on survival was assessed, in particular, the
      repeated use of TIPS and prolonged courses of antibiotics. All four patients had
      thrombosis of their TIPS at the time of diagnosis of enterococcal bacteremia. All
      were treated with prolonged courses of intravenous antibiotics. One patient had
      echocardiographic evidence of subacute bacterial endocarditis with chronic aortic
      insufficiency. In all cases, liver transplantation was contraindicated in the
      acute setting because of uncontrolled endovascular infection. Two of four
      patients survived; these were the only two patients who had had a successful
      repeat TIPS. Enterococcal bacteremia is a rare complication following TIPS but
      carries a high mortality. It usually occurs in the setting of technically
      difficult TIPS with shunt thrombosis. Management should be focused on long term
      antibiotics and attempts at reestablishment of portal decompression with another
      TIPS. Liver transplantation should not be considered until the infection is
      cleared. Prophylaxis for Enterococcus species should be considered in technically
      difficult or unsuccessful TIPS.

PMID- 9576463
TI  - Diffuse pancreatic fibrosis: an uncommon feature of multifocal idiopathic
      fibrosclerosis.
AB  - Multifocal idiopathic fibrosclerosis (MIF) is a rare syndrome characterized by
      exuberant fibrosis involving diverse organ systems. MIF is manifest by varying
      combinations of the following conditions: mediastinal fibrosis, retroperitoneal
      fibrosis, orbital pseudotumor, Riedel's thyroiditis, and sclerosing cholangitis.
      Less common features of MIF include Dupuytren's contractures, lymphoid
      hyperplasia, Peyronie's disease, vasculitis, testicular fibrosis, and
      pachymeningitis. Fibrosis arising from the pancreas has been previously described
      in two patients with MIF. We report a 58-yr-old white man with MIF manifest as
      orbital pseudotumor, sclerosing cholangitis, lymph node hyperplasia, and diffuse
      pancreatic fibrosis.

PMID- 9576465
TI  - Pneumatosis intestinalis and AIDS: a case report and review of the literature.
AB  - We report five AIDS patients who developed pneumatosis intestinalis and review
      the pertinent literature to clarify the contributory importance of underlying
      infections, to suggest a management plan, and to determine whether pneumatosis
      intestinalis alters prognosis. Of the five patients reported, three had
      concurrent infections including cryptosporidiosis (one patient), presumptive CMV
      (one patient), and toxoplasmosis of the central nervous system (one patient). One
      patient also had neutropenia. Another patient was immunosuppressed during
      treatment for lymphoma, and the fifth patient had been taking corticosteroids
      before the diagnosis of CNS lymphoma. In four of five patients pneumatosis
      involved the right colon. Pneumatosis was linear in all five patients and also
      was cystic in two of the five. All patients were followed conservatively without
      short term adverse events, despite the known association of linear pneumatosis
      with bowel necrosis. We advocate conservative management and an attempt to avoid
      surgery whenever possible.

PMID- 9576464
TI  - Metal stents for the palliation of inoperable upper gastrointestinal stenoses.
AB  - We sought to determine the efficacy of metal stents in the palliation of
      malignant upper gastrointestinal stenoses. Six patients with inoperable malignant
      obstruction of the upper gastrointestinal tract, intractable nausea and vomiting,
      and an inability to maintain an oral intake were studied. A metal stent was
      inserted under endoscopic control and deployed in the stenosis. Stents were
      successfully deployed in all patients, and there were no immediate complications.
      All patients were able to eat after the procedure and parenteral nutrition was
      discontinued in all. Mean survival was 23 +/- 8.6 days. We conclude that metal
      stents represent a promising approach to the management of selected patients with
      malignant upper gastrointestinal stenoses and that their use warrants further
      study.

PMID- 9576466
TI  - Budd-Chiari syndrome related to factor V Leiden mutation.
AB  - We here describe a young patient who presented with chronic Budd-Chiari syndrome.
      An exhaustive etiological investigation to detect a procoagulable state was
      negative except for factor V mutation (factor V Leiden), a factor associated with
      resistance to activated protein C. Factor V Leiden is known to be a common, high
      risk factor for thrombosis. This factor should be routinely investigated in
      patients with Budd-Chiari syndrome, as factor V Leiden mutation is probably the
      procoagulable state responsible for many cases of "idiopathic" Budd-Chiari
      syndrome.

PMID- 9576467
TI  - Immunoblastic lymphadenopathy presenting as an acute abdomen and mixed bacteremia
      with Eikenella corrodens and group C streptococci.
AB  - Eikenella corrodens and group C streptococci have been noted to occur with
      increased frequency in patients with underlying malignancies and
      immunosuppressive states. We report a case where these organisms were isolated
      from a patient with immunoblastic lymphadenopathy and discuss the possible
      association between these two conditions.

PMID- 9576468
TI  - Painless small bowel ischemia presenting with diarrhea and weight loss.
AB  - Chronic ischemia of the small bowel is classically described as presenting with
      abdominal pain associated with eating (intestinal angina). Here we describe the
      cases of two patients with chronic small bowel ischemia who presented atypically
      with painless watery diarrhea and weight loss. These cases suggest that the
      clinical spectrum of chronic small bowel ischemia may be wider than previously
      appreciated. Chronic ischemia of the small bowel should be included in the
      differential diagnosis for painless watery diarrhea in the context of weight
      loss.

PMID- 9576469
TI  - Gallbladder carcinoma in an asymptomatic biliary typhoid carrier: report of a
      case.

PMID- 9576470
TI  - Fournier's gangrene: an unusual presentation for rectal carcinoma.
AB  - We report a case of a large perforated adenocarcinoma of the rectum manifesting
      as an ischiorectal abscess progressing to Fournier's gangrene in an insulin
      dependent diabetic man. Recognition and management of this rare syndrome in the
      setting of a common disease is discussed.

PMID- 9576471
TI  - EUS and rectal cancer staging.

PMID- 9576472
TI  - Inhalation of N2O/O2 versus conscious sedation for colonoscopy.

PMID- 9576473
TI  - Ethanol-acetaminophen cocktail: the debate continues!

PMID- 9576474
TI  - A bone hepatocellular carcinoma metastasis without hepatic tumor: a long-term
      follow-up.

PMID- 9576475
TI  - Re: Is endoscopic common bile duct stenting useful in patients with suspected
      sphincter of Oddi dysfunction?

PMID- 9576476
TI  - High levels of endotoxin antibodies contribute to hyperglobulinemia of cirrhotic
      patients.

PMID- 9576477
TI  - Metabolic features and nutritional status in chronic alcoholics.

PMID- 9576478
TI  - Role of single-stranded DNA regions and Y-box proteins in transcriptional
      regulation of viral and cellular genes.
AB  - Single-stranded regions, known to be important for optimal rates of
      transcription, have been observed in the promoters of several cellular genes as
      well as in the promoters of many pathogenic viruses. Several host-encoded, single
      stranded DNA binding proteins capable of binding these regions have been purified
      and their genes isolated. In this review, information available about single
      stranded regions present within various promoters and the interaction of a novel
      class of single-stranded DNA binding transcription factors belonging to the Y-box
      family of proteins is reviewed. Mechanisms by which these proteins influence
      transcription of both cellular and viral genes are proposed.

PMID- 9576479
TI  - Phosphotransfer reactions in the regulation of ATP-sensitive K+ channels.
AB  - ATP-sensitive K+ (K(ATP)) channels are nucleotide-gated channels that couple the
      metabolic status of a cell with membrane excitability and regulate a number of
      cellular functions, including hormone secretion and cardioprotection. Although
      intracellular ATP is the endogenous inhibitor of K(ATP) channels and ADP serves
      as the channel activator, it is still a matter of debate whether changes in the
      intracellular concentrations of ATP, ADP, and/or in the ATP/ADP ratio could
      account for the transition from the ATP-liganded to the ADP-liganded channel
      state. Here, we overview evidence for the role of cellular phosphotransfer
      cascades in the regulation of K(ATP) channels. The microenvironment of the K(ATP)
      channel harbors several phosphotransfer enzymes, including adenylate, creatine,
      and pyruvate kinases, as well as other glycolytic enzymes that are able to
      transfer phosphoryls between ATP and ADP in the absence of major changes in
      cytosolic levels of adenine nucleotides. These phosphotransfer reactions are
      governed by the metabolic status of a cell, and their phosphotransfer rate
      closely correlates with K(ATP) channel activity. Adenylate kinase catalysis
      accelerates the transition from ATP to ADP, leading to K(ATP) channel opening,
      while phosphotransfers driven by creatine and pyruvate kinases promote ADP to ATP
      transition and channel closure. Thus, through delivery and removal of adenine
      nucleotides at the channel site, phosphotransfer reactions could regulate ATP/ADP
      balance in the immediate vicinity of the channel and thereby the probability of
      K(ATP) channel opening. In this way, phosphotransfer reactions could provide a
      transduction mechanism coupling cellular metabolic signals with K(ATP) channel
      associated functions.

PMID- 9576480
TI  - Differential expression of the Kell blood group and CD10 antigens: two related
      membrane metallopeptidases during differentiation of K562 cells by phorbol ester
      and hemin.
AB  - The erythroleukemic cell line K562 can undergo further differentiation in
      erythroid or megakaryocytic lineage depending on the nature of the stimulus.
      Phorbol ester (PMA) stimulates megakaryocytic development whereas hemin promotes
      erythroid differentiation of these cells. We have examined the effect of PMA and
      hemin on the expression of the Kell blood group and CD10 antigens, two related
      proteins that belong to a family of membrane-bound neutral metalloendopeptidases.
      We show here that differentiation of K562 cells by PMA in the megakaryocytic
      lineage results in abolishment of Kell mRNA accumulation and protein expression
      and, in parallel, the induction of CD10 mRNA accumulation, protein expression,
      and enzymatic activity. Conversely, differentiation of these cells by hemin in
      the erythroid lineage is accompanied by an up-regulation of Kell mRNA and protein
      expression, with no changes in CD10 mRNA and protein expression. Thus, CD10 and
      Kell can be regarded as specific markers of the differentiation of K562 cells in
      the megakaryocytic and erythroid lineages, respectively.

PMID- 9576481
TI  - The secondary alcohol metabolite of doxorubicin irreversibly inactivates
      aconitase/iron regulatory protein-1 in cytosolic fractions from human myocardium.
AB  - Anticancer therapy with doxorubicin (DOX) is limited by severe cardiotoxicity,
      presumably reflecting the intramyocardial formation of drug metabolites that
      alter cell constituents and functions. In a previous study, we showed that NADPH
      supplemented cytosolic fractions from human myocardial samples can enzymatically
      reduce a carbonyl group in the side chain of DOX, yielding a secondary alcohol
      metabolite called doxorubicinol (DOXol). Here we demonstrate that DOXol
      delocalizes low molecular weight Fe(II) from the [4Fe-4S] cluster of cytoplasmic
      aconitase. Iron delocalization proceeds through the reoxidation of DOXol to DOX
      and liberates DOX-Fe(II) complexes as ultimate by-products. Under physiologic
      conditions, cluster disassembly abolishes aconitase activity and forms an
      apoprotein that binds to mRNAs, coordinately increasing the synthesis of
      transferrin receptor but decreasing that of ferritin. Aconitase is thus converted
      into an iron regulatory protein-1 (IRP-1) that causes iron uptake to prevail over
      sequestration, forming a pool of free iron that is used for metabolic functions.
      Conversely, cluster reassembly converts IRP-1 back to aconitase, providing a
      regulatory mechanism to decrease free iron when it exceeds metabolic
      requirements. In contrast to these physiologic mechanisms, DOXol-dependent iron
      release and cluster disassembly not only abolish aconitase activity, but also
      affect irreversibly the ability of the apoprotein to function as IRP-1 or to
      reincorporate iron within new Fe-S motifs. This damage is mediated by DOX-Fe(II)
      complexes and reflects oxidative modifications of -SH residues having the dual
      role to coordinate cluster assembly and facilitate interactions of IRP-1 with
      mRNAs. Collectively, these findings describe a novel mechanism of cardiotoxicity,
      suggesting that intramyocardial formation of DOXol may perturb the homeostatic
      processes associated with cluster assembly or disassembly and the reversible
      switch between aconitase and IRP-1. These results may also provide a guideline to
      design new drugs that mitigate the cardiotoxicity of DOX.

PMID- 9576482
TI  - Influence of heat shock on cell volume regulation: protection from hypertonic
      challenge in a human monocyte cell line.
AB  - Heat shock response provides cells with higher tolerance against a variety of
      insults such as heavy metals, reperfusion injury, and endotoxin. In addition,
      heat treatment is known to affect ion transport mechanisms associated with vital
      cellular processes, including cell volume regulation. However, there has been no
      reports to date of a heat shock effect on cellular volume regulation itself. The
      aim of our study was to investigate whether the heat shock response influences
      volume regulation of cells. Human promonocytic U937 cells display an increase in
      volume in response to osmotic shrinkage. This regulatory volume increase (RVI) is
      mediated mainly by ion antiporters. U937 cells exposed to a temperature of 45
      degrees C for 10 min (heat shock) show an enhancement of RVI after hypertonic
      challenge compared with untreated cells. Also, heat-treated cells display a lower
      intracellular pH (pHi) than untreated cells; similar control mechanisms are
      believed to be involved in regulating both pHi and RVI. In agreement with this,
      heat-shocked cells demonstrated increased activity of an HCO3(-)-independent/DIDS
      sensitive pHi down-regulator, postulated to be a Cl-/HCO3- exchange. We suggest
      that heat shock-mediated RVI enhancement is at least partially mediated by an
      increased Cl-/HCO3- exchange. Our results indicate that heat shock of U937 cells
      activates a hitherto unknown cytoprotective effect that may help cells to
      overcome hypertonic challenge.

PMID- 9576483
TI  - Redox regulation of ubiquitin-conjugating enzymes: mechanistic insights using the
      thiol-specific oxidant diamide.
AB  - The ubiquitin-proteasome pathway (UPP) regulates critical cell processes,
      including the cell cycle, cytokine-induced gene expression, differentiation, and
      cell death. Recently we demonstrated that this pathway responds to oxidative
      stress in mammalian cells and proposed that activities of ubiquitin-activating
      enzyme (E1) and ubiquitin-conjugating enzymes (E2s) are regulated by cellular
      redox status (i.e., GSSG:GSH ratio). To test this hypothesis, we altered the
      GSSG:GSH ratio in retinal pigment epithelial cells with the thiol-specific
      oxidant, diamide, and assessed activities of the UPP. Treatment of cells with
      diamide resulted in a dose-dependent increase in the GSSG:GSH ratio resulting
      from loss of GSH and a coincident increase in GSSG. Increases in the GSSG:GSH
      ratio from 0.02 in untreated cells to > or = 0.5 in diamide-treated cells were
      accompanied by dose-dependent reductions in the levels of endogenous Ub-protein
      conjugates, endogenous E1-ubiquitin thiol esters, and de novo ubiquitin
      conjugating activity. As determined by the ability to form E1-ubiquitin and E2s
      ubiquitin thiol esters, E1 and E2s were both inhibited by elevated GSSG:GSH
      ratios. Inhibition of E1 was associated with the formation of E1-protein mixed
      disulfides. Activities of E1 and E2s gradually recovered to preoxidation levels,
      coincident with gradual recovery of the GSSG:GSH ratio. These data support S
      thiolation/dethiolation as a mechanism regulating E1 and E2 activities in
      response to oxidant insult. Ubiquitin-dependent proteolytic capacity was
      regulated by the GSSG:GSH ratio in a manner consistent with altered ubiquitin
      conjugating activity. However, ubiquitin-independent proteolysis was unaffected
      by changes in the GSSG:GSH ratio. Potential adaptive and pathological
      consequences of redox regulation of UPP activities are discussed.

PMID- 9576484
TI  - Swelling detection for volume regulation in the primitive eukaryote Giardia
      intestinalis: a common feature of volume detection in present-day eukaryotes.
AB  - It is increasingly evident that cell swelling is associated with the triggering
      of many biological processes, including progression of the cell cycle, hormonal
      response, and gene expression. However, the mechanism by which cell swelling is
      initially sensed and converted into intracellular signals is still ill-defined.
      We report here an early event in the detection of cell swelling and initiation of
      the volume regulatory response in Giardia intestinalis, an ancient representative
      of the eukaryotic kingdom. Giardial cell swelling, irrespective of the extent,
      was sensed at a cell volume of 1.06 x isosmotic volume (the threshold volume), at
      which the transition of the volume regulatory transport system from the 'resting'
      to the 'open' state occurred. Irreversible modification by p
      chloromercuribenzoate (pCMB) and N-ethylmaleimide (NEM) of reduced thiols
      affected the threshold volume, but in opposing manners: pCMB increased the
      threshold volume to 1.14 x and NEM decreased to 0.85 x isosmotic volume. The
      simple modification of the threshold volume by NEM caused a drastic reduction of
      giardial cell volume under isosmotic conditions, with a process strikingly
      similar to the opening of mitochondrial permeability transition pore, a causative
      event in stress-induced programmed cell death. Substantial evidence supports the
      hypothesis that modulation of the membrane thiol moieties at the threshold
      volume, causing the 'all-or-nothing' type of swelling detection, represents the
      event linking cell swelling to the second messenger systems for volume regulation
      in present eukaryotes. Pathophysiological implications of alteration of the
      threshold volume are discussed.

PMID- 9576485
TI  - CD38 is functionally dependent on the TCR/CD3 complex in human T cells.
AB  - One of the functions of surface CD38 is the induction of phosphorylation of
      discrete cytoplasmic substrates and mobilization of cytoplasmic calcium (Ca2+).
      The present work addresses the issue of whether the signaling mediated via CD38
      operates through an independent pathway or, alternatively, is linked to the
      TCR/CD3 signaling machinery. We studied the signals elicited through CD38 by the
      specific agonistic IB4 monoclonal antibody (mAb) by monitoring the levels of
      cytoplasmic Ca2+ and the induced phenotypic and functional variations in T cell
      growth. IB4 mAb presented the unique ability to increase cytoplasmic Ca2+ levels,
      which correlated with the phosphorylation of the PLC-gamma1. These effects were
      blocked by phorbol 12-myristate 13-acetate (PMA) and were dependent on the
      presence of a functional TCR/CD3 surface complex, no effects being recorded on
      mutant Jurkat cells lacking part of the CD3 structures. CD38 signaling appeared
      to share with TCR/CD3 the ability to induce apoptotic cell death in Jurkat T
      cells, an event paralleled by specific up-regulation of the Fas molecule and
      inhibited by cyclosporin A. CD28, a costimulatory molecule, is synergized by
      increasing CD38-induced apoptotic cell death. The results indicate the existence
      of a strong functional interdependence between CD38 and TCR/CD3.

PMID- 9576486
TI  - L-type calcium channel expression depends on the differentiated state of vascular
      smooth muscle cells.
AB  - Despite intensive interest in understanding the differentiation of vascular
      smooth muscle cells (VSMC), no information is available about differential
      regulation of ion channels in these cells. Since expression of the L-type Ca2+
      channel can be influenced by differentiation in other cell types, we tested the
      hypothesis that the L-type (C class) channel is a specific differentiation marker
      of VSMC and that expression of these channels depends on the state of cell
      differentiation. We used rat aortic (A7r5) VSMC, which express functional L-type
      Ca2+ channels, and induced dedifferentiation by cell culture in different media.
      Treatment with retinoic acid was used to redifferentiate the VSMC. We
      characterized the differentiated state of the cells by using immunohistochemistry
      and Western blot analysis for smooth muscle (SM) alpha-actin and SM-myosin heavy
      chain (MHC). The number of functional Ca2+ channels was significantly decreased
      in dedifferentiated VSMC and increased upon differentiation with retinoic acid.
      Ca2+ channel function was assessed by whole-cell voltage clamp techniques. Using
      Western blot and dihydropyridine binding analysis, we found that the expression
      of the Ca2+ channel alpha1 subunit, and to a lesser extent the beta2 subunit, was
      directly correlated with the expression of SM alpha-actin and SM-MHC. We conclude
      that expression of L-type Ca2+ channel alpha1 subunits, and thus a functional
      Ca2+ channel, is highly coordinated with expression of the SM-specific proteins
      required for specialized smooth muscle cell functions. Furthermore, our results
      demonstrate that the L-type Ca2+ channel is a novel marker for differentiation of
      VSMC. The data suggest that regulation of ion channel expression during
      differentiation may have physiological importance for normal smooth muscle
      function and may influence VSMC behavior under pathophysiological conditions.

PMID- 9576487
TI  - Sulfation in high endothelial venules: cloning and expression of the human PAPS
      synthetase.
AB  - High endothelial venules (HEVs) are specialized postcapillary venules found in
      lymphoid organs and chronically inflamed tissues that support high levels of
      lymphocyte extravasation from the blood. Studies with chlorate, a metabolic
      inhibitor of sulfation, had previously revealed that production of PAPS (3'
      phosphoadenosine-5'-phosphosulfate), the high-energy donor of sulfate, is
      required for sulfation and high-affinity recognition of HEV sialomucins GlyCAM-1
      and CD34 by the lymphocyte homing receptor L-selectin. Here, we report the
      molecular characterization of a novel 2.5 kb human cDNA from MECA-79+ HEV-derived
      endothelial cells that encodes the target of chlorate, PAPS synthetase, a
      multifunctional enzyme containing domains for both ATP sulfurylase and adenosine
      5'-phosphosulfate kinase. Functional expression of the isolated cDNA in Chinese
      hamster ovary cells results in high levels of PAPS synthesis, which is abolished
      by treatment of the transfected cells with chlorate. Northern blot analysis
      reveals a wide tissue distribution of PAPS synthetase mRNA in the human body,
      suggesting that human PAPS synthetase may be important for sulfation not only of
      HEV sialomucins, but also of many other molecules, including mucins such as the P
      selectin ligand PSGL-1, proteoglycans, hormones, neurotransmitters, drugs, and
      xenobiotics.

PMID- 9576488
TI  - Environmental estrogenic pollutants induce acute vascular relaxation by
      inhibiting L-type Ca2+ channels in smooth muscle cells.
AB  - There is an ongoing scientific debate concerning the potential threat of
      environmental estrogenic pollutants to animal and human health (1-5). Pollutants
      including the detergents 4-octylphenol and p-nonylphenol and chlorinated
      insecticides have recently been reported to modulate sexual differentiation by
      interacting with nuclear steroid receptors (6-8). So far, the focus has been on
      reproductive organs, but sex steroids have far more widespread actions. The lower
      incidence of cardiovascular disease in women has been attributed to estrogens (9
      14), yet no information is available on the vascular actions of environmental
      estrogenic pollutants. In the present study we have investigated the effects of
      acute exposure to 17beta-estradiol, the antiestrogen ICI 182,780, and estrogenic
      pollutants on coronary vascular tone as well as on intracellular Ca2+ levels
      ([Ca2+]i) and Ca2+ and K+ channel activity in vascular smooth muscle cells. We
      report here that 4-octylphenol, p-nonylphenol, o.p'-DDT, and the antiestrogen ICI
      182,780 inhibit L-type Ca2+ channels in vascular smooth muscle cells and evoke a
      rapid and endothelium-independent relaxation of the coronary vasculature similar
      to that induced by 17beta-estradiol. Thus, inhibition of Ca2+ influx via L-type
      Ca2+ channels in vascular smooth muscle cells may explain the acute, nongenomic
      vasodilator actions of environmental estrogenic pollutants.

PMID- 9576489
TI  - Trichinella spiralis: vascular endothelial growth factor is up-regulated within
      the nurse cell during the early phase of its formation.
AB  - The L1 larval stage of Trichinella spiralis induces modification in a portion of
      striated skeletal muscle cell resulting in the formation of the nurse cell. This
      specialized host cell is completely encased in a capsule composed mainly of
      collagen type IV and type VI, which, in turn, is surrounded by a unique rete of
      vessels whose formation begins on around day 12 after intracellular infection. We
      investigated the possibility that vascular endothelial growth factor (VEGF) may
      be up-regulated during nurse cell formation by employing immunohistochemistry and
      in situ hybridization on synchronously infected mouse muscle tissue. Both VEGF
      mRNA and VEGF peptide were detected in the developing nurse cell cytoplasm from
      day 7 up to 16 mo after infection. In addition, VEGF was also detected in cells
      in the area immediately surrounding the nurse cell on days 15 and 17. On the
      basis of these results, we propose that hypoxia is induced by T. spiralis within
      the developing nurse cell some time prior to the up-regulation of VEGF, perhaps
      as early as day 7. We further propose, on the basis of the continued presence of
      VEGF in nurse cell cytoplasm, that a constant state of hypoxia cell is
      maintained.

PMID- 9576490
TI  - Influence of culture method on Steinernema glaseri lipids.
AB  - Entomopathogenic nematodes can be mass produced in artificial media for use as
      biological insecticides. Nematode in vitro media have been primarily developed on
      the basis of yield without fully considering nematode nutritional requirements.
      We investigated the quality and quantity of lipids in the entomopathogenic
      nematode Steinernema glaseri when grown in vivo in Popillia japonica (a natural
      host), Galleria mellonella (a factitious host), and in solid and liquid media.
      Nematode yield (infective juveniles per mg dry organic material) was 4 times
      higher in the in vivo compared with the in vitro cultures. Nematodes produced in
      vivo using P. japonica accumulated a significantly higher amount of lipids
      compared with nematodes grown using G. mellonella or in vitro solid and liquid
      methods, respectively. Fractionation of S. glaseri total lipids revealed that
      nematodes produced using P. japonica accumulated significantly higher
      phospholipids and sterols compared with other methods. C:18 fatty acids were the
      predominant class of lipids in S. glaseri irrespective of production method. In
      vivo-produced nematodes had oleic 18:1 acid as the major fatty acid, whereas in
      vitro-produced S. glaseri had a mixture of oleic 18:1 and linoleic 18:2 acids as
      the predominant fatty acids. We conclude that the lipid composition of
      entomopathogenic nematode is host or medium dependent. We suggest that adjusting
      the in vivo medium by addition of components similar to a natural host
      nutritional composition should improve nematode production.

PMID- 9576491
TI  - Metabolic changes in Giardia intestinalis during differentiation.
AB  - The oxygen uptake rate and metronidazole (MTZ) sensitivity in Giardia spp. cysts
      is greatly reduced from that in trophozoites. Thus, this project was undertaken
      to assess when in the encystation process these phenomena occur. Oxygen uptake
      rates approximately doubled (from approximately 4.9 to 8.3 microM O2 min(-1) 10(
      6) cells) during the first 5 hr into encystation. This increase was followed by a
      marked decrease to 2.3 microM O2 min(-1) 10(-6) by 12 hr. By 50 hr into
      encystation, oxygen uptake was 0.7 microM O2 min(-1) 10(-6) cells. Glucose
      stimulated oxygen uptake by 89% in trophozoites but did not demonstrably
      stimulate oxygen uptake in cells after 12 hr into encystment. Deoxy-D-glucose
      uptake dropped by more than an order of magnitude in encysting cells compared to
      nonencysting cells. In contrast, aspartate uptake remained relatively constant
      regardless of whether cells were encysting or not. This suggests that there is a
      change in the parasite's ability to transport glucose during cyst formation; a
      similar change in the parasite's ability to transport aspartate was not observed
      after 40 hr into encystation. MTZ inhibited oxygen uptake by 77% in trophozoites,
      but there was no detectable inhibition of oxygen uptake 8 hr after trophozoites
      were transferred to encystation medium. We propose that this resistance to MTZ
      may be due to a change in metabolic flux away from the pyruvate ferredoxin
      oxidoreductase pathway. Oxygen uptake by noninduced cysts increased exponentially
      during the 30 min following the induction of excystation. Likewise, MTZ
      sensitivity returned within 15 min after the induction of excystation, and by 30
      min into excystation full sensitivity had returned.

PMID- 9576492
TI  - Comparison of Echinostoma caproni mother sporocyst development in vivo and in
      vitro using Biomphalaria glabrata snails and a B. glabrata embryonic cell line.
AB  - Biomphalaria glabrata embryonic (Bge) cells have previously been shown to permit
      a successful cocultivation of Schistosoma mansoni and Schistosoma japonicum from
      miracidia to mother sporocysts (MS) and then to the production of daughter
      sporocysts (DS). To investigate further the properties of the Bge culturing
      system we used Echinostoma caproni under identical in vitro conditions. In vitro
      derived miracidia were used either for experimental infections of B. glabrata
      snails, or for in vitro cultivation with Bge cells. Histological analysis showed
      that the development of MS in B. glabrata was similar to the previously described
      development in Biomphalaria pfeifferi in terms of final site of infection,
      development dynamics, growth dynamics, reproduction intensity, and life spans.
      Only short delays in migration dynamics were observed in B. glabrata. When
      cultivated under in vitro conditions, E. caproni MS could live for up to 17 wk in
      the presence of Bge cells, as compared with 2 wk in cell-free Bge medium. The
      presence of Bge cells also permitted significant growth of MS and development
      through complete embryogenesis of the next intramolluscan stage (embryos of 100
      110 cells). However, degeneration of MS consistently occurred before production
      of this second generation. During the entire cultivation period, no visible
      contact was observed between MS and Bge cells, suggesting that development of MS
      was only triggered by soluble factors released by Bge cells.

PMID- 9576493
TI  - Gill parasites of mummichogs, Fundulus heteroclitus (Teleostei: Cyprinodontidae):
      effects of season, locality, and host sex and size.
AB  - I investigated the prevalences and densities of gill parasites in 4 seasonal
      samples of mummichog, Fundulus heteroclitus (n=242), from 2 creeks differing in
      salinity in central Chesapeake Bay. The parasites (and overall prevalence ranges)
      were: mobile (12-88%) and sessile (0-50%) peritrichs (Ciliophora); Myxobolus
      funduli (58-94%) (Myxozoa); Gyrodactylidae (0-94%) (includes Gyrodactylus sp. and
      Fundulotrema sp.) and Salsuginus sp. (74-100%) (Monogenea); metacercariae of
      Phagicola diminuta (75-100%) and Echinochasmus schwartzi (79-100%) (Digenea);
      Ergasilus manicatus (25-100%) (Copepoda); Lironeca ovalis (0-11%) (Isopoda); and
      cysts of unknown etiology, or CUEs (64-94%) (unknown taxon). CUEs were more
      abundant in fall and gyrodactylids in winter. The myxozoan, copepod, and 1
      species of digenean were most abundant in spring. Except for gyrodactylids and
      CUEs, densities were greater in the less saline creek for all taxa. There were no
      significant differences between sexes except in 1 sample; digenean densities
      increased with host length for females but not males. There was a strong positive
      relationship of CUE density with host length and weaker positive associations of
      gyrodactylid and Salsuginus sp. densities with host length.

PMID- 9576494
TI  - Niche overlap among three species of pinworm parasitic in the hindgut of the
      American cockroach, Periplaneta americana.
AB  - Individual American cockroaches, Periplaneta americana, often harbor 3 species of
      pinworm (Oxyurida: Nematoda) Thelastoma bulhoesi, Leidynema appendiculatum, and
      Hammerschmidtiella diesingi, simultaneously. We looked for evidence of trophic
      niche segregation based on differences in size preference among the 3 species.
      Fluorescent beads of 1, 3, 6, and 10 microm diameter were mixed in agar and fed
      to individual hosts. Adult female worms of each species were removed from hosts,
      and the number of each size of bead in each worm was assessed. Horn's R0 and
      Hurlbert's L indices of niche overlap were calculated for infracommunities
      containing at least 1 of each species. Hurlbert's index extends the information
      given by Horn's index to include the effects of proportional availability of each
      resource. Both indices indicated a lack of trophic segregation based on particle
      size among the 3 species. Species did, however, differ in consumption rate: L.
      appendiculatum ate more than T. bulhoesi, which ate more than H. diesingi.

PMID- 9576495
TI  - Composition and structure of helminth communities of the salamanders, Aneides
      lugubris, Batrachoseps nigriventris, Ensatina eschscholtzii (Plethodontidae), and
      Taricha torosa (Salamandridae) from California.
AB  - Component helminth communities of Aneides lugubris (N=31), Batrachoseps
      nigriventris (N=63), Ensatina eschscholtzii (N=30), and Taricha torosa (N=68)
      from California were determined. The compound helminth community consisted of 1
      species of cestode, Bitegmen gerrhonoti and 6 species of nematodes,
      Batracholandros salamandrae, Cosmocercoides variabilis, Falcaustra pretiosa,
      Megalobatrachonema gigantica, Oswaldocruzia pipiens, and Rhabdias joaquinensis.
      The least diverse infracommunities were associated with Batrachoseps nigriventris
      while T. torosa had the most diverse fauna. Only B. salamandrae occurred in each
      of the 4 component communities. Each of the other helminth species was harbored
      by a single host species. New host records for B. salamandrae in B. nigriventris
      and T. torosa; O. pipiens in A. lugubris; C. variabilis in E. eschscholtzii; F.
      pretiosa and M. gigantica in T. torosa are established.

PMID- 9576496
TI  - Transmission and natural regulation of infection with Ascaris lumbricoides in a
      rural community in China.
AB  - A longitudinal study on a cohort of 215 people who remained untreated from June
      1993 to June 1994 was carried out using fecal egg counts to examine the course of
      transmission and aspects of the natural regulation of the infection with Ascaris
      lumbricoides. The results indicate that the parasite population remained
      relatively stable during the years since overall prevalence remained steady above
      60%. About 40% of the people in the cohort retained their infection intensity
      status throughout the year, in terms of light, medium, and heavy infections. The
      regulation of infection in the population could be attributed to the tendency for
      the loss of worms from people with initial light infections and the movement to
      medium infection intensity status of people with both light and heavy infections.
      Compared with adults, children showed a stronger tendency of retaining initial
      medium infections but weaker tendencies for keeping initial light infections and
      clearing themselves of infection. Predisposition to light and medium infections
      was detected in people who had experienced an uninfected period of 4-12 mo before
      reinfection was established.

PMID- 9576497
TI  - Larval trematode assemblages in the snail Lymnaea stagnalis from southeastern
      Wisconsin.
AB  - From May through November 1993 and 1994, Lymnaea stagnalis appressa were
      collected from a stream adjacent to Cedarburg Bog, Ozaukee County, Wisconsin.
      Observations of cercarial shedding and subsequent dissection of snails revealed a
      relatively depauperate digenean component community consisting primarily of 3
      common species. The most frequently occurring form was the metacercaria of
      Cotylurus flabelliformis. Sporocysts and cercariae of this species were rarely
      observed. Snails also harbored sporocysts and shed cercariae of Schistosomatium
      douthitti and a plagiorchid. Seasonal and yearly dynamics of the component
      trematode community reflect the apparent inability of sporocysts to overwinter in
      snails at this location. They also seem to be associated closely with snail life
      histories in terms of the availability of large snails, most often infected by
      the sporocysts of S. douthitti and the plagiorchid. Analyses of double infections
      revealed the occurrence of a negative interspecific interaction between the
      tetracotyles of C. flabelliformis and sporocysts of S. douthitti. Other
      combinations of trematode species did not reveal negative interactions.
      Competition does not seem to play a major role in the structure of the component
      community at this location.

PMID- 9576498
TI  - Growth and structural features of the adult stage of Ascaris suum (Nematoda,
      Ascaridoidea) from experimentally infected domestic pigs.
AB  - For studying the morphogenesis of the adult stage of Ascaris suum, worms were
      obtained from experimentally infected domestic pigs. Structural and morphometric
      features of A. suum are analyzed by light and scanning electron microscopy. It
      was shown that the increase in length of the worm from days 35 to 56 is based on
      a region-specific lengthening of individual transverse annuli in the cuticle. An
      increased worm size also results in an increased diameter of different cuticular
      sense organs. It is shown that a pair of lateral midbody papillae, the centrids,
      are prominent sensilla in the adult male and female worm. The centrids have an
      asymmetric placement, the right centrid being more anterior on the worm than the
      left.

PMID- 9576499
TI  - Plasmodium inui is not closely related to other quartan Plasmodium species.
AB  - Plasmodium inui (Halberstaedter and von Prowazek, 1907), a malarial parasite of
      Old World monkeys that occurs in isolated pockets throughout the Celebes,
      Indonesia, Malaysia, and the Philippines, has traditionally been considered to be
      related more closely to Plasmodium malariae of humans (and its primate
      counterpart Plasmodium brasilianum), than to other primate Plasmodium species.
      This inference was made in part because of the similarities in the periodicities
      or duration of the asexual cycle in the blood, the extended sporogonic cycle, and
      the longer period of time for development of the pre-erythrocytic stages in the
      liver. Both P. inui and P. malariae have quartan (72 hr) periodicities associated
      with their asexual cycle, whereas other primate malarias, such as Plasmodium
      fragile and Plasmodium cynomolgi, are associated with tertian periodicities (48
      hr), and Plasmodiumn knowlesi, with a quotidian (24 hr) periodicity. Phylogenetic
      analyses of portions of orthologous small subunit ribosomal genes reveal that P.
      inui is actually more closely related to the Plasmodium species of the "vivax
      type" lineage than to P. malariae. Ribosomal sequence analysis of many different,
      geographically isolated, antigenically distinct P. inui isolates reveals that the
      isolates are nearly identical in sequence and thus members of the same species.

PMID- 9576500
TI  - Characterization of a relatively rare class B, type 2 trypanosome variant surface
      glycoprotein gene.
AB  - The variant surface glycoprotein (VSG) gene of Trypanosoma brucei rhodesiense
      LouTat 1.5, a defined African trypanosome variant antigenic type, was cloned and
      sequenced. Southern blot analysis revealed 2 DNA restriction fragments in both
      VSG 1.5 expressor and nonexpressor populations, suggesting that there are 2
      genomic copies of the VSG 1.5 gene and no expression-linked copies. Pulsed-field
      gel electrophoresis followed by Southern blot analysis showed that each copy of
      the VSG 1.5 gene exists on a separate large chromosome in both the expressor
      (approximately 3.5- and 4-megabase (Mb) chromosomes) and nonexpressor
      (approximately 4- and 5.7-Mb chromosomes) populations. Thus, VSG genes may be
      present on larger chromosomes than previously reported. Sequence analysis and
      alignments revealed that the VSG 1.5 molecule is a class B VSG with 12 cysteine
      residues in the N-terminus and is classified as a type 2 VSG based on C-terminus
      motifs. This classification shows that the VSG 1.5 molecule represents a
      relatively rare VSG class and type. Taken together, these studies provide
      additional information on VSG genes and proteins and supply the foundation for
      structure-function analysis of the VSG 1.5 surface antigen expressed by
      trypanosomes of the LouTat 1 serodeme.

PMID- 9576501
TI  - The sequence of Giardia small subunit rRNA shows that voles and muskrats are
      parasitized by a unique species Giardia microti.
AB  - The small subunit ribosomal RNA (eukaryotic 16S rRNA) gene from Giardia
      trophozoites, isolated from 8 different prairie voles and 8 different muskrats,
      was amplified by the polymerase chain reaction. The 16S rDNA was sequenced in its
      entirety for 2 prairie vole and 2 muskrat Giardia. In addition, the 5' 500
      nucleotides of the 16S rDNA from Giardia isolates from each of 6 voles and 6
      muskrats were amplified and sequenced. The results show that Giardia from voles
      and muskrats are very similar to each other but differ substantially from Giardia
      isolated from humans. We believe that the Giardia isolate from voles and muskrats
      constitutes a distinct species, which will be referred to as Giardia microti.
      These results suggest that both voles and muskrats are parasitized by the same
      species of Giardia, that this species is different from the Giardia that
      parasitizes humans, and that voles and muskrats do not contribute to the zoonotic
      character of human giardiasis.

PMID- 9576503
TI  - Identification of a new fluke allergen identified by monoclonal IgE antibodies
      for Paragonimus miyazakii.
AB  - IgE-producing hybridomas were acquired from fusing splenic cells to myeloma cells
      of BALB/c mice infected with Paragonimus miyazakii. With the use of the
      monoclonal antibody (mAb)xIgE obtained, the localization of the allergen in P.
      miyazakii, as well as its molecular weight, was evaluated. The allergen was
      present in the gut epithelium and luminal contents of adult flukes. Because this
      allergen was absent in the related species Paragonimus westermani and Paragonimus
      ohirai, we believe that it is specific to P. miyazakii. The allergen was
      estimated to be less than 14,400 daltons and was 1 of the smallest components
      that appeared after electrophoresis.

PMID- 9576502
TI  - Immunochemical purification and characterization of a 74.0-kDa Schistosoma
      mansoni antigen.
AB  - A polypeptide antigen of 74.0 kDa molecular weight was detected in the antigenic
      extracts of the 3 developmental stages of Schistosoma mansoni (eggs, cercariae,
      and adult worms) by western blotting using BRL4 monoclonal antibody (mAb) that
      significantly protected mice at the levels of 51.6%, 42%, and 53.8% against
      challenge S. mansoni infection in 3 separate experiments. This antigen was
      isolated and purified from crude soluble worm antigen preparation by
      immunoaffinity chromatography using CNBr-activated sepharose-4B beads coupled
      with the BRL4 mAb. The purified antigen showed a single peak when analyzed by
      both high-performance liquid chromatography and high-performance capillary
      electrophoresis. The 74-kDa antigen was characterized as a protein in nature with
      56.9% hydrophilic amino acids and 43.1% hydrophobic amino acids. This antigen was
      detected in 93% of urine samples from infected cases with specificity of 89%
      among noninfected cases using an enzyme immunoassay-fast dot-enzyme-linked
      immunosorbent assay based on BRL4 mAb.

PMID- 9576504
TI  - Vaccination of mice with Neospora caninum: response to oral challenge with
      Toxoplasma gondii oocysts.
AB  - Neospora caninum is a protozoan parasite that can cause severe disease in
      mammals. Two experiments were conducted to examine the effects of subcutaneous
      (s.c.) vaccination with Hank's balanced salt solution (HBSS), 1 x 10(5) N.
      caninum NC-1 strain tachyzoites or 1 x 10(5) Toxoplasma gondii TS-4 strain
      tachyzoites on challenge oral infections in mice with sporulated VEG strain T.
      gondii oocysts (1 X 10(3) oocysts exp. 1 and 5 x 10(3) oocysts exp. 2). An
      additional study, experiment 3, evaluated s.c. challenge with 2.5 X 10(3)
      tachyzoites of the highly virulent RH strain of T. gondii after vaccination with
      HBSS, NC-1 tachyzoites, or TS-4 tachyzoites. Mice vaccinated with NC-1 strain
      tachyzoites survived significantly (P < 0.05) longer than mice given HBSS in
      experiment 1, but not in experiments 2 and 3. Mice vaccinated with TS-4 strain
      tachyzoites survived significantly longer than HBSS-vaccinated mice in
      experiments 1, 2, and 3 and significantly longer than mice vaccinated with the NC
      1 strain in experiments 2 and 3. Toxoplasma gondii tissue cyst numbers were
      significantly lower for mice vaccinated with TS-4 strain tachyzoites than mice
      vaccinated with HBSS or the NC-1 strain tachyzoites in experiment 1. No
      difference was observed in tissue cyst numbers in mice vaccinated with HBSS or NC
      1 strain tachyzoites in experiment 1. No HBSS-vaccinated mice survived experiment
      2, and the numbers of T. gondii tissue cysts were significantly lower for mice
      vaccinated with the TS-4 strain tachyzoites compared to NC-1 strain tachyzoites.
      No HBSS- or NC-1-vaccinated mice survived RH strain challenge in experiment 3.
      Results of these experiments indicate that infection with N. caninum provides
      some protection against fatal oral infection with T gondii oocysts of a
      moderately pathogenic strain but not tachyzoites of a highly pathogenic strain.
      The protection provided by N. caninum is much less than that provided by previous
      exposure to T. gondii, and the numbers of tissue cysts in the brains of mice are
      not significantly (P > 00.5) lowered.

PMID- 9576505
TI  - Comparison of intracerebral parasite load, lesion development, and systemic
      cytokines in mouse strains infected with Neospora caninum.
AB  - Neospora caninum, an apicomplexan parasite closely related to Toxoplasma gondii,
      causes abortion, stillbirths, and congenital neurologic disease in multiple
      animal species. The present study focuses on the development of encephalitis and
      intracerebral parasite load that occurs 6 wk postinfection (PI). Utilizing
      BALB/c, C57BL/6, and B10.D2 mice, an initial investigation was undertaken to
      determine the relative resistance of inbred strains to N. caninum-induced
      encephalitis. Relative resistance was defined in terms of central nervous system
      lesion development and parasite load. Based on other protozoal infections in
      mice, it was hypothesized that BALB/c and C57BL/6 should be contrasting in their
      relative resistance to N. caninum, with BALB/c and congenic B10.D2 mice less
      susceptible than C57BL/6 mice. Contrary to expectation, BALB/c and C57BL/6 were
      both highly susceptible to the development of N. caninum-induced encephalitis,
      whereas B10.D2 mice were resistant. Both BALB/c mice and C57BL/6 mice had
      significantly higher numbers of brain lesions and intracerebral tachyzoites than
      B10.D2 mice. Resistance in B10.D2 was associated with a high interferon (IFN)
      gamma: interleukin (IL)-4 ratio from antigen-stimulated splenocytes, whereas
      susceptibility in C57BL/6 and BALB/c mice corresponded with a low splenocyte IFN
      gamma: IL-4 ratio. In vivo measurement of Neospora-specific isotype antibodies
      demonstrated predominately IgG2a in serum from B10.D2 mice and IgG1 in serum from
      BALB/c and C57BL/6 mice. In conclusion, susceptibility of mice to N. caninum is
      unique compared to other protozoal diseases. The present study also demonstrates
      that parasite load is a fundamental measurement for evaluating disease induced by
      N. caninum and that a type 1 cytokine response may be necessary for regulation of
      this parameter.

PMID- 9576506
TI  - Genital and systemic immune responses in a murine model of Tritrichomonas foetus
      infection.
AB  - A reliable laboratory animal model would be useful for the study of immune
      responses to trichomoniasis, a sexually transmitted disease of human beings and
      cattle. Murine models are available, but pretreatment with estrogen is used,
      which may influence immune responses. To evaluate whether vaginal trichomoniasis
      could be established in nonestrogenized mice and to define the immune responses
      associated with the infection, CD1 and BALB/c mice were studied with or without
      estrogen treatment prior to inoculation with Tritrichomonas foetus.
      Tritrichomonas Foetus was cultured from the vagina and uterus of both estrogen
      treated and untreated control mice for up to 26 wk. The infection was sustained
      better in BALB/c than in CD1 mice, suggesting that the former strain was most
      susceptible. In CD1 mice, infection was sustained less well in estrogen-treated
      than in untreated control mice, but there was no difference between treatment
      groups of BALB/c mice. IgA and IgG antibodies in vaginal secretions, uterine
      secretions, and serum specific for a surface antigen of T. foetus (TF1.17) were
      measured by enzyme-linked immunosorbent assay. In infected CD1 mice, vaginal IgA
      and IgG antibodies were detected by 8 wk postinoculation (PI). In infected BALB/c
      mice, vaginal IgA and IgG antibodies were detected by 12 wk PI. Uterine IgG
      responses predominated over IgA in estrogen-treated and untreated CD1 and BALB/c
      mice. There were high levels of IgG, but relatively no IgA in the sera of CD1 and
      BALB/c mice. Overall, the highest IgA response was in the vaginal secretions of
      infected CD1 mice, and some animals of this strain cleared the infection. These
      results show that a chronic trichomonad infection was established in mice without
      prior treatment with estrogen. The infection was associated with antibody
      responses in reproductive secretions and serum. This animal model will be useful
      in studying immunization to protect against trichomoniasis in mice not
      immunocompromised by estrogen.

PMID- 9576507
TI  - Cellular dynamics and cytokine responses in BALB/c mice infected with Eimeria
      papillata during primary and secondary infections.
AB  - BALB/c mice were infected with the intestinal intracellular parasite Eimeria
      papillata to characterize lymphocyte responses and cytokine profiles throughout
      primary and secondary infections. Lymphocytes from the mesenteric lymph node
      (MLN) and the gastrointestinal tract (GIT) of infected mice were phenotypically
      analyzed using flow cytometry and immunofluorescence microscopy, respectively.
      Lymphocytes isolated from the MLN during primary infections of BALB/c mice with
      E. papillata do not proliferate, compared to day 0 uninfected controls, when
      stimulated in vitro with conconavalin A and express TH2-type cytokines
      (interleukin [IL]-4 and IL-10) on day 3 PI followed by the release of TH1-type
      cytokines (IL-2 and interferon-gamma) during patency. In the small intestine,
      significantly more T cells and their subsets were observed during primary
      infection. During secondary infections, IL-2 was the only 1 of the 4 cytokines
      that was expressed earlier and at higher levels in the MLN when compared to
      primary infections. In the small intestine, significantly more alphabeta+ and
      CD8+ T lymphocytes were observed in mice during secondary infection. Oocyst
      antigens did not induce cellular proliferation at any time point during primary
      or secondary infections. We conclude that primary oral infection of BALB/c mice
      with E. papillata is associated with localized immunosuppression that may be
      mediated, in part, by early TH2-type cytokines. Immunity to secondary infection
      may be mediated by intestinal alphabeta+ CD8+ T lymphocytes through an IL-2
      dependent mechanism.

PMID- 9576508
TI  - Resistance of Acanthamoeba species to complement lysis.
AB  - Acanthamoeba species were evaluated for susceptibility to complement lysis as
      determined by release of radiolabeled uridine. The 3 Acanthamoeba species tested,
      A. culbertsoni (ATCC 30171), A. castellanii (ATCC 30010), and A. polyphaga (ATCC
      30461), depleted hemolytic complement activity from normal human serum (NHS), yet
      were resistant to its lytic effects. Examination of microtiter plates containing
      amoebae incubated in NHS demonstrated formation of a pellet in the wells. Pellet
      formation was not observed when amoebae were incubated in human cord serum, heat
      inactivated serum, or C1q-deficient serum. Ultrastructural examination of serum
      treated amoebae revealed the presence of a finely granular substance that
      surrounded the amoebae. Treatment of amoebae with enzymes or metabolic inhibitors
      prior to incubation in NHS was performed to investigate the mechanism of
      complement resistance. Cycloheximide or cytochalasin D pretreatment increased the
      susceptibility of A. culbertsoni and A. castellanii to complement lysis.
      Cytochalasin D treatment also increased the susceptibility of A. polyphaga to
      complement lysis. Inhibition of serine protease activity by
      phenylmethylsulfonylfluoride increased complement susceptibility of all 3 species
      of Acanthamoeba. Enzymatic removal of surface components from A. polyphaga or A.
      castellanii, with trypsin, neuraminidase, or phosphatidylinositol-specific
      phospholipase C (PIPLC), did not affect serum resistance. In contrast, PIPLC
      treatment of A. culbertsoni significantly increased lysis by complement. The
      ability of Acanthamoeba species to activate the alternative complement pathway
      yet resist complement-mediated cellular lysis can be attributed to both the
      release of a transport-dependent extracellular matrix as well as the presence of
      complement inhibitory surface proteins.

PMID- 9576509
TI  - Cercarial production of the trematode Rhipidocotyle fennica in clams kept in the
      field.
AB  - The numbers of cercariae that trematodes produce have been previously
      investigated in the laboratory but not in the field. I studied cercarial
      production of the bucephalid trematode Rhipidocotyle fennica in the freshwater
      unionid clam Anodonta piscinalis kept under natural conditions. Naturally
      infected clams (n=180) were collected and marked in early June 1996. Every 14
      days, starting from the collection date and ending in October, these clams were
      taken to the laboratory where they were monitored for the emergence of trematode
      cercariae. Between monitoring dates, the clams were returned to the collection
      site. From a random subsample of infected clams (n=12), the number of cercariae
      produced was counted during every monitoring. Cercarial production started in
      late July. The proportion of infected clams releasing cercariae increased from
      late July to late August. The mean daily production also increased during that
      period from 140 to 10,400 cercariae, decreasing thereafter. The mean annual
      production was 290,000+/-26,000 (160,000-440,000) cercariae. Daily production in
      late August and early September was positively correlated with annual production.
      Two of the 12 clams appeared to be infected with both R. fennica and
      Rhipidocotyle campanula. The average annual productions of R. fennica and R.
      campanula cercariae in double infections were 181,000+/-58,000 and 73,000+/
      29,000, respectively.

PMID- 9576511
TI  - Cloning and characterization of cDNAs encoding beta-tubulin from Dirofilaria
      immitis and Onchocerca volvulus.
AB  - Beta-Tubulin is the target for the benzimidazole anthelmintics. Unfortunately,
      none of these drugs is clinically useful against adult filariae. However, beta
      tubulin has been shown to be a target for antibody-based toxicity to Brugia
      pahangi. We cloned and characterized cDNAs encoding beta-tubulin from 2 filariae,
      Dirofilaria immitis and Onchocerca volvulus, to explore possible explanations for
      benzimidazole insensitivity among adult filariae and the likelihood that epitopes
      of beta-tubulin could be used as antigens for a broad-spectrum filarial vaccine.
      The proteins predicted by these cDNAs were almost identical to the beta-tubulin
      previously reported from B. pahangi but were less similar to a beta-tubulin cDNA
      from Onchocerca gibsoni. We cloned the genomic locus for the O. volvulus beta
      tubulin cDNA and compared its organization to the reported genomic loci for beta
      tubulin in B. pahangi and O. gibsoni. The comparison reinforces the conclusion
      that the published O. gibsoni gene is in a different family, possibly the beta2
      family previously described in B. pahangi. The substitution of tyr for phe at
      position 200 of beta-tubulin is associated with benzimidazole resistance. All 4
      filarial beta-tubulins are predicted to encode phe at this position, suggesting
      that filarial beta-tubulin is not inherently insensitive to the benzimidazoles. A
      monoclonal antibody that recognizes the COOH terminus of B. pahangi beta-tubulin
      is lethal to this parasite in culture. The COOH terminal region is the most
      variable among the different isotypes of beta-tubulin and distinguishes mammalian
      from nematode tubulins. This region is highly conserved in 3 of the filarial beta
      tubulins.

PMID- 9576510
TI  - Purification and characterization of a 16-kDa cysteine proteinase of
      Gymnophalloides seoi (Gymnophallidae) metacercariae.
AB  - Gymnophalloides seoi, a new human intestinal trematode transmitted by oysters, is
      highly prevalent in southwestern coastal areas of Korea. The aim of this
      preliminary study was to acquire an understanding of the pathogenesis of G. seoi
      infection, and, to this end, we followed 2 consecutive steps, Sephacryl S-300 HR
      and CM-Trisacryl M chromatography, to purifiy a 16-kDa proteinase from crude
      extract of G. seoi metacercariae. Enzyme activities were completely inhibited by
      L-trans-epoxysuccinylleucylamide (4-guanidino) butane (E-64) and iodoacetic acid,
      cysteine proteinase inhibitors, strongly suggesting that the enzyme is a cysteine
      proteinase. Activity of the proteinase was maximal at pH 5.0 in 0.1 M of buffer
      and potentiated in the presence of 5 mM dithiothreitol. The proteinase showed
      differential abilities to hydrolyze macromolecules and immunoglobulins; it
      completely degraded extracellular matrix proteins such as collagen and
      fibronectin during overnight incubation but digested hemoglobin very slowly. The
      proteinase also cleaved human immunoglobulins IgG2a and sIgA; heavy chains were
      more susceptible than light chains to its digestive activity. The proteinase
      showed no antigenicity on both enzyme-linked immunosorbent assay and immunoblots,
      however. Our results strongly suggest that the cysteine proteinase of G. seoi
      metacercariae is potentially significant in nutrient uptake and evasion by the
      worm of the host immune response.

PMID- 9576512
TI  - Identification of electrophoretically separated proteases from midgut and
      hemolymph of adult Anopheles stephensi mosquitoes.
AB  - Digestion of blood within the mosquito midgut is mediated primarily by a series
      of proteases, and several previous studies have described protease activity
      within homogenates of the midgut of the malaria vector Anopheles stephensi. We
      have expanded on these previous data by resolving protease isoforms from the
      midgut as well as the hemolymph of adult An. stephensi mosquitoes via gel
      electrophoresis and zymography. Using this procedure, we have been able to
      identify multiple isozymes of trypsin, chymotrypsin, and aminopeptidase. We were
      able to detect an increase in the intensity of some of these protease bands plus
      the appearance of new bands 24 hr after mosquitoes had taken a blood meal.
      Furthermore, we detected 2 endogenous trypsin isozymes within the hemolymph.
      There was no upregulation of these hemolymph isozymes after a blood meal, thus
      suggesting that they may not be involved in digestion of the blood meal by the
      mosquito.

PMID- 9576513
TI  - Hastospiculum spiralis n. sp. (Nematoda: Diplotriaenoidea: Dicheilonematinae),
      from an Indonesian mangrove monitor, Varanus indicus (Reptilia: Sauria:
      Varanidae).
AB  - While examining an imported Indonesian mangrove monitor, Varanus indicus
      (Reptilia: Sauria: Varanidae), for helminths, a new species of Hastospiculum was
      collected and is described as Hastospiculum spiralis n. sp. This species differs
      from all other members of the genus in caudal papillae number and arrangement, a
      pair of large cephalic papillae, and a spirally twisted left spicule in males.
      Additionally, H. spiralis n. sp. differs from certain Hastospiculum species by
      the right and left spicule lengths, egg shape, and the final host.

PMID- 9576514
TI  - Species of Myxobolus (Myxozoa) from the bulbus arteriosus of centrarchid fishes
      in North America, with a description of two new species.
AB  - Three species of Myxobolus (Myxozoa, Myxosporea) occur in heart tissue of
      centrarchids. Myxobolus paralintoni Li and Desser, 1985 from Lepomis gibbosus in
      Algonquin Park and in Lake Erie, Ontario, has subcircular spores (in plane of
      spore length) in frontal view (11-13 microm long, 9-10 microm wide, and 5 microm
      thick) with a width-to-length ratio of 1:1.2. Myxobolus jollimorei n. sp. from
      Lepomis macrochirus in Lake Erie and in the Pascagoula River System, Mississippi,
      has subcircular spores (in plane of spore width) in frontal view (10.0-11.5
      microm long, 12.0-14.5 microm wide, and 6.5-8.0 microm thick) with a width-to
      length ratio of 1:0.8. Myxobolus manueli n. sp. from Pomoxis nigromaculatus in
      Lake Erie has spores (10-11 microm long, 8-10 microm wide, and 6.5-7.0 microm
      thick) that are nearly circular in frontal view but that have 2 distinct
      sublateral knobs along the sutural ridge and a width-to-length ratio of 1:1.2.
      All 3 species occur in the bulbus arteriosus of their hosts where they form
      small, saucer-shaped pseudocysts. Free spores were found free in the lumen of the
      heart and bulbus arteriosus, in bile, and in kidney tissue presses.

PMID- 9576515
TI  - Hapalotrema (Digenea: Spirorchidae) in the green turtle (Chelonia mydas) in
      Australia.
AB  - Hapalotrema mehrai Rao, 1976 and Hapalotrema postorchis Rao, 1976 (Digenea:
      Spirorchidae) are redescribed from the heart and pulmonary arteries of the green
      turtle, Chelonia mydas, from Moreton Bay in south-eastern Queensland. Hapalotrema
      pambanensis Gupta and Mehrotra, 1981 from C. mydas in India is made a synonym of
      H. mehrai. Hapalotrema dorsopora Dailey, Fast and Balazs, 1993 from C. mydas from
      Hawaii was described with a dorsally opening uterine pore, but this is found to
      be the opening of Laurer's canal; therefore H. dorsopora is also made a synonym
      of H. mehrai. In addition to differences in the numbers of testes and general
      dimensions, H. mehrai and H. postorchis differ in the development of Laurer's
      canal and in the absence of a canalicular seminal receptacle in H. postorchis.

PMID- 9576516
TI  - The phylogenetic placement of Taenia cestodes that parasitize humans.
AB  - We estimated phylogenetic relationships among 12 species or variants of the
      cestode genus Taenia, including all 3 species that typically use humans as the
      definitive host, using published sequences of cytochrome c oxidase subunit I
      (COI) and 28s rDNA. Analyses of all the data combined using maximum parsimony,
      neighbor-joining, and maximum likelihood methods give well resolved trees. The
      trees are similar regardless of the analytical method used. Most of the
      phylogenetically informative characters are contained in the COI sequence, and
      trees obtained from analyses of COI alone are similar to the combined data trees.
      All of the phylogeny estimates suggest that Taenia tapeworms have switched from
      carnivore definitive hosts to human definitive hosts twice in their history. This
      result is also supported by bootstrap analyses using all 3 of the above methods
      of phylogeny estimation.

PMID- 9576517
TI  - Spermatozoa as phylogenetic characters for the Eucestoda.
AB  - Spermatozoon ultrastructure and spermiogenesis are significant characters for
      phylogenetic inference. Sperm ultrastructure is reviewed from the literature in
      56 species of Eucestoda. Data are available for 11 of the 12 orders of Eucestoda
      (Lecanicephalidea excepted), but in some orders data are scarce and often limited
      to a single species. Spermiogenesis and sperm ultrastructure in the Eucestoda is
      compared to that of other parasitic Platyhelminthes, with emphasis on structures
      of phylogenetic interest. Not only the descriptions of sperm structure, but those
      of the process of spermiogenesis, are necessary to define characters.
      Synapomorphies based on sperm ultrastructure for the Eucestoda include the
      absence of a mitochondrion in mature sperm and the presence of a crested body. A
      proposed synapomorphy for the Cyclophyllidea + Tetrabothriidea is the twisting of
      the peripheral microtubules; the absence of intercentriolar body and the absence
      of striated roots in the spermatid may constitute additional synapomorphies for
      this assemblage. Absence of flagellar rotation during spermiogenesis is
      synapomorphic for the Cyclophyllidea, and absence of proximodistal fusion could
      be synapomorphic for a part of the Cyclophyllidea. Several other characters could
      be useful for understanding phylogeny within the Eucestoda. The polarity of these
      characters could in several cases be determined, but diagnoses for taxa or
      relationships based on synapomorphies cannot be specified unequivocally due to
      putative convergence. Such characters and their putative polarity include: (1)
      the number of axonemes in mature spermatozoon (plesiomorphic=2; apomorphic=1);
      (2) size and number of crested bodies (p=1; a=several); and (3) angle of twisted
      microtubules; shape of nucleus (p=compact cord; a=crescent and annulus).
      Additional apomorphic attributes include (1) presence of a periaxonemal sheath (a
      putative synapomorphy for the Cyclophyllidea + Tetrabothriidea if reversals are
      postulated in certain cyclophyllideans); (2) presence of proteinaceous transverse
      walls; (3) presence of dense granules; and (4) shape of apical cones and
      posterior structures. Studies of sperm structure in the poorly known orders and
      additional comparative studies in the Cyclophyllidea are expected to provide new
      information for elucidation of phylogenetic relationships.

PMID- 9576519
TI  - Babesia bennetti n. sp. from the yellow-legged gull (Larus cachinnans, Aves,
      Laridae) on Benidorm Island, Mediterranean Sea.
AB  - Babesia bennetti sp. nov. is described as a new species of piroplasm parasitizing
      the yellow-legged gull Larus cachinnans. This is the first report of Babesia for
      this family of birds. Double infections in the erythrocytes were common. The
      udder cow forms described in Babesia peircei also were found in this species. The
      typical "X" forms are rarely seen, with merozoites commonly found in pairs as
      tetrads.

PMID- 9576518
TI  - Three new genera and species of tapeworms from the longnose sawshark,
      Pristiophorus cirratus, with comments on their modes of attachment to the spiral
      intestine.
AB  - The spiral intestines of 18 specimens of the longnose sawshark Pristiophorus
      cirratus, collected from southeastern Australia, were examined for parasites.
      Three new genera and species of tetraphyllidean tapeworms belonging to the
      Phyllobothriinae within the Phyllobothriidae were discovered as a result of these
      necropsies. Flexibothrium ruhnkei n. g., n. sp. differs from all other
      phyllobothriine tapeworms in its possession of bothridia that each bear an apical
      sucker and a posterior margin that is flexed anteriorly and fused along the
      median line of the distal bothridial surface, forming 2 essentially open-faced
      grooves. Light and scanning electron microscopy of worms attached to the mucosal
      surface suggest that this species uses the open-faced bothridial grooves, the
      outermost surface of the anteriorly flexed portion of each bothridium, and the
      interbothridial surfaces to grasp up to a total of 16 mucosal villi and/or
      ridges. Cardiobothrium beveridgei n. g., n. sp. is unique among the
      phyllobothriids in its possession of bothridia each with an apical sucker,
      marginal loculi, and 4 facial loculi arranged in 2 tandem pairs. This taxon is
      provisionally placed within the Phyllobothriinae, and the subfamilial diagnosis
      is emended to include species with facial loculi. Examination of specimens fixed
      in situ and then removed from the mucosal surface suggests that this species uses
      the larger, posterior pair of facial loculi of each bothridium to grasp the tips
      of a pair of adjacent villi in order to attach to the mucosal surface.
      Bibursibothrium gouldeni n. g., n. sp. also appears to belong in the
      Phyllobothriinae. Within this subfamily it most closely resembles species of
      Marsupiobothrium in its possession of pouchlike bothridia. However, it
      conspicuously differs from species in this genus in that its bothridial pouches
      are subdivided internally into 2 distinct compartments. Cross sections of
      individuals of this taxon attached to the mucosal surface indicate that each
      bothridium is used to grasp 2 adjacent mucosal elements such that the scolex has
      the ability to attach to up to a total of 8 villi and/or ridges. The discovery of
      3 new genera of tapeworms from this host species is not unexpected given the high
      degree of host specificity generally exhibited by the phyllobothriids, and that
      this is the first report of tapeworms from a shark of the order
      Pristiophoriformes.

PMID- 9576520
TI  - Crocodylocapillaria longiovata n. gen., n. sp. (Nematoda: Capillariidae) from the
      stomach of crocodiles in Australia and New Guinea.
AB  - A new nematode, Crocodylocapillaria longiovata n. gen. and n. sp., is described
      from the stomach of wild and farmed young crocodiles, Crocodylus johnstoni
      Krefft, and Crocodylus porosus Schneider, from northern Australia and Papua New
      Guinea; it is undoubtedly identical with the nematodes previously reported as
      Capillaria sp. from Crocodylus novaequineae Schmidt from Irian Jaya, Indonesia.
      This capillariid species represents a new genus, being characterized mainly by
      the presence of elongate eggs with unusually long protruding polar plugs, a well
      developed vulvar appendage, a weakly sclerotized spicule, proximal and distal
      parts of the spicular sheath with spines, and the male posterior end with 2 large
      lateral caudal lobes and a pair of papillae near the cloacal opening. The body
      length of C. longiovara males and females is 5,576-7,208 microm and 8,609-14,008
      microm, respectively, the spicule is 276-369 microm long; the size of the egg
      proper is 48-60 x 15-21 microm, length of polar plugs 15-18 microm. Neocapillaria
      Yi and Guitang, 1994, a junior homonym of Neocapillaria Moravec, 1987, is re
      named Sinocapillaria nom. n. and placed as a synonym of Pseudocapillaria Freitas,
      1959. Indocapillaria De and Maity, 1995 is retained as a subgenus of
      Pseudocapillaria because of the possession of a vulvar appendage in the type
      species. Neocapillaria Moravec, 1987 remains a subgenus of Capillaria Zeder,
      1800. A key to genera of the Capillariidae from poikilotherm vertebrates is
      provided; C. longiovata is the first capillariid species described from the
      digestive tract of crocodiles.

PMID- 9576521
TI  - Occurrence and morphological comparisons of Campula oblonga (Digenea:
      Campulidae), including a report from an atypical host, the thresher shark,
      Alopias vulpinus.
AB  - New host records for Campula oblonga Cobbold, 1858 from the common dolphin,
      Delphinus delphis L., and from the thresher shark, Alopias vulpinus (Bonnaterre),
      are reported herein. Campulids have not been reported previously from a host that
      was not a marine mammal. The excellent condition and small size of the gravid
      specimen and the diet and natural history of the thresher shark lead us to
      conclude that the digene was acquired from the consumption of infected fish.
      Specimens of C. oblonga from these 2 hosts and from harbor porpoises, Phocoena
      phocoena (L.), and from Dall's porpoises, Phocoenoides dalli (True), are
      compared, and a wide variation in ranges and values for characters is noted. The
      synonymy of Campula folium Ozaki, 1935 with C. oblonga is further supported by
      the apparent effect of the host on the size of the trematodes. Due to the degree
      of variation in measurements and the numerous factors that may impact these
      values, we recommend the use of qualitative morphologic characters for the
      identification of C. oblonga.

PMID- 9576522
TI  - Toxoplasma gondii in Vancouver Island cougars (Felis concolor vancouverensis):
      serology and oocyst shedding.
AB  - One of 12 necropsied cougars (Felis concolor vancouverensis) from Vancouver
      Island, British Columbia, Canada, shed Toxoplasma gondii oocysts confirmed by
      mouse bioassay. Eleven of the 12 cougars (92%) had antibodies to T. gondii by the
      modified agglutination test with titers of <1:25 (1 cougar), 1:50 (8 cougars),
      and 1:500 (3 cougars). One additional cougar fecal sample collected from the
      Victoria watershed environment also contained T. gondii oocysts. In 1995, the
      largest reported outbreak of human toxoplasmosis was linked to municipal drinking
      water in Victoria, British Columbia. This study supports the initial hypothesis
      at the time of the outbreak that not only domestic cats, but also cougars, pose a
      risk to Victoria's water supply.

PMID- 9576523
TI  - Strongyloides stercoralis host-adapted third-stage larvae are the target of
      eosinophil-associated immune-mediated killing in mice.
AB  - Host-adapted, transformed, Strongyloides stercoralis third-stage larvae (L3+)
      were previously found to be antigenically different from free-living, infective,
      third-stage larvae (L3). These antigenic differences were reproduced by
      transformation of free-living larvae in tissue culture medium at 37 C over 24 hr.
      Transformed L3 of both derivations were given as challenge infections in
      diffusion chambers to naive mice and mice immunized with S. stercoralis L3.
      Within 12 hr, the challenge infections were killed regardless of whether the L3+
      were generated in vitro or in vivo. Eosinophils, previously found to be important
      in the immune response to S. stercoralis larvae, were recruited into the L3+
      microenvironment within 12 hr of challenge infection in immune mice, which
      supports the previously proposed mechanisms of S. stercoralis larval killing.
      Thus, S. stercoralis L3+ appear to be targets of the immune response in mice
      instead of being involved in immune evasion.

PMID- 9576524
TI  - Taxonomic status of the Japanese triploid forms of Fasciola: comparison of
      mitochondrial ND1 and COI sequences with F. hepatica and F. gigantica.
AB  - Because it is difficult to identify morphologically the Japanese forms of
      Fasciola, additional taxonomic criteria are required. In order to clarify the
      genetic relationships between Fasciola hepatica, Fasciola gigantica, and the
      Japanese triploid forms of Fasciola, we compared nucleotide sequences of
      mitochondrial NADH dehydrogenase subunit 1 (ND1) and cytochrome c oxidase subunit
      I (COI) genes. Intraspecific variation in the ND1 and COI sequences was low,
      except for 1 specimen of F. gigantica in the ND1 sequence. The ND1 and COI
      sequences of Japanese triploid forms of Fasciola were nearly identical to those
      found in F. gigantica but were different from those of F. hepatica. Thus, the
      Japanese triploid forms of Fasciola are thought to be categorized as F.
      gigantica.

PMID- 9576526
TI  - Muscular Sarcocystis infection in a bear (Ursus americanus).
AB  - Sarcocysts of an unidentified Sarcocystis species were found in sections of
      skeletal muscles of a black bear (Ursus americanus) from North Carolina. Two
      sarcocysts in a section measured 45 x 37.5 microm and 67.5 x 50 microm and had a
      thin (<2 microm) sarcocyst wall. The villar protrusions on the cyst wall were up
      to 2 microm long and up to 0.7 microm wide. The bradyzoites were approximately 6
      X 2.5 microm in size. This is the first report of muscular Sarcocystis in a bear.

PMID- 9576525
TI  - Persistence of antibodies against epitopes encoded by a single gene copy of the
      Babesia bovis merozoite surface antigen 1 (MSA-1).
AB  - The Babesia bovis merozoite surface antigen-1 (MSA-1) is an immunodominant,
      neutralization-sensitive merozoite surface antigen encoded by a polymorphic gene
      family. MSA-1 antigenic polymorphism results in a complete lack of immunologic
      cross-reactivity among strains. It is unknown how rapidly this antigenic shift
      occurs, or whether it evolves in the mammalian host. To determine whether the
      dominant epitopes encoded by a single msa-1 gene copy vary during the course of a
      single infection, the antibody response to these epitopes was measured after
      infection of cattle with the Mo7 biologically cloned strain of B. bovis using an
      Mo7 gene copy-specific enzyme-linked immunosorbent assay. Antibodies against MSA
      1 encoded by this gene copy were detected by postinoculation (PI) day 15 in each
      of 5 experimentally infected animals. Importantly, detectable antibody persisted
      in all carrier animals without a significant decrease in optical density through
      12 mo PI, at which time the experiment was terminated. The results indicate that
      immunodominant epitopes expressed by a single gene copy of msa-1 do not undergo
      marked antigenic shift typical of the gene family during the course of a single
      infection in the mammalian host. The results are compatible with the limited MSA
      1 polymorphism reported in some geographically defined endemic populations.

PMID- 9576527
TI  - Fish as paratenic hosts of Serpinema trispinosum (Leidy, 1852) (Nematoda:
      Camallanidae).
AB  - Third-stage larvae of the nematode Serpinema trispinosum (Leidy, 1852) were
      collected from the intestine of the freshwater cichlid, Cichlasoma urophthalmus
      (Gunther), from a small lake in Yucatan, Mexico. This is the first record of
      Serpinema larvae from fishes, and their presence may reflect the importance of
      fishes as paratenic hosts of turtle parasites in this genus.

PMID- 9576528
TI  - Improvement in the identification of intestinal parasites by a concentrated
      merthiolate-iodine-formaldehyde technique.
AB  - To increase the sensitivity of the merthiolate-iodine formaldehyde (MIF)
      technique in detecting various stages of intestinal parasites in stool specimens,
      a concentration step was added before preserving the stool specimen with MIF
      solution. This step involved mixing the stool specimen in 10% formalin, filtering
      the mixture through a double-layered cotton filter, and removing most of the
      liquid content. This modification was evaluated in a large screening program. Its
      positive identification of 10 helminths and 2 protozoa was comparable to formalin
      ethyl acetate (FEA) sedimentation and hookworm eggs were readily recognizable.
      Although the modified MIF technique requires an overnight drying procedure, only
      a few simple procedures are involved in the concentrating step. This technique is
      relatively simple and suitable for large-scale screening programs or
      epidemiologic studies.

PMID- 9576529
TI  - The molecular genetics of the dystonias.

PMID- 9576530
TI  - The importance of mental fatigue.

PMID- 9576531
TI  - Relation between neuropsychological impairment and functional disability in
      patients with chronic fatigue syndrome.
AB  - OBJECTIVES: To examine the relation between neuropsychological impairment and
      functional disability in patients with chronic fatigue syndrome, and determine
      whether the relation is independent of psychiatric factors. METHODS: The subjects
      were 53 patients with chronic fatigue syndrome and 32 healthy controls who did
      not exercise regularly. Subjects were administered a structured psychiatric
      interview and completed questionnaires focusing on depression and functional
      disability. They also completed a battery of standardised neuropsychological
      tasks focusing on the cognitive domains that patients with chronic fatigue
      syndrome experience as particularly difficult: memory (verbal and visual), and
      attention/concentration. A test score was defined as failing when it was > or =2
      SD below the mean of the healthy controls after controlling for demographic
      factors. RESULTS: Those patients with chronic fatigue syndrome with higher
      numbers of failing neuropsychological test scores reported significantly more
      days of general inactivity in the past month than those with fewer failing
      scores. This result remained significant even after partialling out the
      contribution of the presence of a comorbid axis I psychiatric episode and the
      overall level of depressive symptomology. Patients with failing verbal memory
      scores were particularly functionally disabled compared with those with passing
      scores. CONCLUSION: A relation was found between cognitive impairment and
      functional disability which could not be explained entirely on the basis of
      psychiatric factors.

PMID- 9576532
TI  - Transient epileptic amnesia: a description of the clinical and neuropsychological
      features in 10 cases and a review of the literature.
AB  - OBJECTIVES: To clarify the clinical and neuropsychological aspects of transient
      epileptic amnesia (TEA) based on 10 personally studied cases as well as review of
      21 previously published cases; and to propose tentative diagnostic criteria for
      the diagnosis of TEA. METHODS: All 10 patients and informants underwent a
      standardised clinical interview. The radiological and neurophysiological (EEG)
      data were also reviewed in all cases. The diagnosis of transient epileptic
      amnesia was made on the basis of the following criteria: (1) there was a history
      of recurrent witnessed episodes of transient amnesia; (2) cognitive functions
      other than memory were judged to be intact during typical episodes by a reliable
      witness; (3) there was evidence for a diagnosis of epilepsy. This evidence was
      provided by either (a) wake or sleep EEG, or (b) the co-occurrence of other
      seizure types (if their roughly concurrent onset or close association with
      episodes of transient amnesia suggested a connection), or (c) a clear cut
      response to anticonvulsant therapy, or by a combination of these three factors.
      In addition all patients were administered a comprehensive neuropsychological
      test battery designed to assess verbal and non-verbal anterograde memory and
      retrograde memory for famous personalities and personal events. Their results
      were compared with those of 25 age and IQ matched normal controls. RESULTS: TEA
      usually begins in later life, with a mean age of 65 years in this series.
      Episodes are typically brief, lasting less than one hour, and recurrent, with a
      mean frequency of three a year. Attacks on waking are characteristic. Repetitive
      questioning occurs commonly during attacks. The anterograde amnesia during
      episodes is, however, often incomplete so that patients may later be able to
      "remember not being able to remember". The extent of the retrograde amnesia
      during attacks varies from days to years. Most patients experience other seizure
      types compatible with an origin in the temporal lobes, but transient amnesia is
      the only manifestation of epilepsy in about one third of patients. Epileptiform
      abnormalities arising from the temporal lobes are most often detected on
      interictal sleep EEG. Despite normal performance on tests of anterograde memory,
      many patients complain of persistent interictal disturbance of autobiographical
      memory, involving a significant but variable loss of recall for salient personal
      episodes. The epochs affected may predate the onset of epilepsy by many years.
      CONCLUSIONS: TEA is an identifiable syndrome and comprises episodic transient
      amnesia with an epileptic basis, without impairment of other aspects of cognitive
      function. Future studies should consider the question of whether TEA reflects
      ictal activity or a postictal state, and the mechanism of the persistent
      autobiographical amnesia. It is hypothesised that the latter may result in part
      from impairment of very long term memory consolidation as a result of epileptic
      activity in mesial temporal structures.

PMID- 9576533
TI  - Utilisation and cost of professional care and assistance according to disability
      of patients with multiple sclerosis in Flanders (Belgium)
AB  - OBJECTIVES: To assess the utilisation of medical services and social (community)
      assistance in patients with multiple sclerosis of different disability and to
      calculate the direct healthcare costs to society. METHODS: (1) One hundred and
      eighty four patients with multiple sclerosis were classified into four grades of
      disability according to a simplified Kurzke disability status scale. (2) Patients
      were interviewed with a structured questionnaire containing questions on their
      sociodemographic status, the use of inpatient and outpatient medical services and
      pharmaceutical products during the previous year, the use of social assistance,
      and the purchase of prosthetics and charges for house adaptations during the
      previous five years. (3) Data were also prospectively collected by means of four
      week diary annotations of all medical and social acts and their duration.
      RESULTS: After correction for the disability distribution the yearly costs for
      the 5500 patients with multiple sclerosis in Flanders was estimated to be ECU
      13106000 for ambulatory care including rehabilitation and district nursing and
      ECU 3234000 for pharmaceutical products. To these direct medical costs ECU
      3491000 for social assistance and ECU 4938000 for prosthetics and adaptations
      should be added. The yearly costs for admissions to hospital including permanent
      residence in an institution and pharmacy was ECU 26581000 . Home nursing and long
      term or permanent residence in an institution of the most severely disabled, 17%
      of the multiple sclerosis population, are responsible for 50% of the total direct
      healthcare costs and care for the 6.5% institutionalised patients accounts for
      23%. Direct costs for medical care and social assistance for patients with
      multiple sclerosis, who account for about 0.1 % of the total population, amounts
      to 1% of the total healthcare budget in Flanders. CONCLUSION: This information on
      utilisation of medical services and social assistance can be used for good
      healthcare planning and cost effectiveness studies.

PMID- 9576534
TI  - Clinical study of primary progressive multiple sclerosis in Northern Ireland, UK.
AB  - OBJECTIVE: To investigate the clinical and demographic characteristics of primary
      progressive multiple sclerosis (PPMS) in Northern Ireland and to establish a
      database of such patients for genetic and immunological studies and future
      therapeutic trials. METHODS: Diagnosis and categorisation were performed by two
      neurologists, potential cases being identified from the following sources:
      neurology outpatient clinics; neurology inpatients; a review of hospital
      discharges; and an ongoing epidemiological study of multiple sclerosis in
      Northern Ireland. Only those with a progressive course from onset and a clear
      history of no prior relapses were accepted. Potential cases were invited for
      interview and assessment, the minimal record of disability (MRD) being
      established. RESULTS: One hundred and eleven cases of PPMS have been identified,
      63 women and 48 men (ratio 1.3:1), with a mean age at onset of 39.5 (SD 11.0)
      (range 17-66)years, and mean disease duration of 13.6 (SD 9.3)years. The mean
      interval between onset and diagnosis was 4.7 (SD 4.2) years. Nineteen patients
      (17.1%) did not satisfy the requirements for any category in the Poser criteria.
      Motor disturbance was the commonest mode of onset (67.6%) with visual loss
      occurring only rarely at onset (3.6%). Kurtzke EDSS scores were concentrated at
      the upper end of the scale with a median of 6.0 and levels of unemployment and
      financial dependence were high. CONCLUSIONS: PPMS in Northern Ireland has a
      generally later age at onset, lower female preponderance, and predominantly motor
      onset compared with other subgroups of multiple sclerosis. The delay to diagnosis
      reflects the often insidious onset and the nature of the clinical course makes
      application of the Poser criteria difficult. Levels of neurological impairment,
      disability, and handicap as measured by the MRD are high.

PMID- 9576535
TI  - Computer assisted retraining of attentional impairments in patients with multiple
      sclerosis.
AB  - OBJECTIVE: To evaluate the efficacy of a computer based retraining of specific
      impairments of four different attentional domains in patients with multiple
      sclerosis. METHODS: Twenty two outpatients with multiple sclerosis received
      consecutively a specific training comprising 12 sessions in each of the two most
      impaired attention functions. The baseline of attentional deficits, the
      performance after each training period, and the course of performance in the next
      nine weeks was assessed by a computerised attention test battery. Additionally,
      the impact of the training on daily functioning was evaluated with a self rating
      inventory. RESULTS: Subgroups of patients with multiple sclerosis showing
      different patterns of attentional impairment could be separated. Significant
      improvements of performance could almost exclusively be achieved by the specific
      training programmes. The increase of performance remained stable for at least
      nine weeks. For quality of life patients reported less attention related problems
      in everyday situations. CONCLUSIONS: In patients with multiple sclerosis it seems
      worthwhile to assess attentional functions in detail and to train specific
      attention impairments selectively.

PMID- 9576536
TI  - Poisoning by organophosphorus insecticides and sensory neuropathy.
AB  - OBJECTIVES: Poisoning by organophosphate insecticides causes cholinergic
      toxicity. Organophosphate induced delayed polyneuropathy (OPIDP) is a sensory
      motor distal axonopathy which usually occurs after ingestion of large doses of
      certain organophosphate insecticides and has so far only been reported in
      patients with preceding cholinergic toxicity. Surprisingly, it was recently
      reported by other authors that an exclusively sensory neuropathy developed in
      eight patients after repeated unquantified exposures to chlorpyrifos, which did
      not cause clear-cut cholinergic toxicity. The objective was to assess whether an
      exclusively sensory neuropathy develops in patients severely poisoned by various
      OPs. METHODS: Toxicological studies and electrophysiological measurements were
      performed in peripheral motor and sensory nerves in 11 patients after acute
      organophosphate poisoning among which two subjects were poisoned with
      chlorpyrifos. RESULTS: Three patients developed OPIDP, including one poisoned by
      chlorpyrifos. Exclusively sensory neuropathy was never seen after either single
      or repeated acute organophosphate poisoning. A mild sensory component was
      associated with a severe motor component in two of the three cases of OPIDP, the
      other was an exclusively motor polyneuropathy. CONCLUSION: A sensory-motor
      polyneuropathy caused by organophosphate insecticides might occur after a severe
      poisoning and the sensory component, if present, is milder than the motor one.
      Bearing in mind the toxicological characteristics of these organophosphate
      insecticides, other causes should be sought for sensory peripheral neuropathies
      in patients who did not display severe cholinergic toxicity a few weeks before
      the onset of symptoms and signs.

PMID- 9576537
TI  - Clinical similarities of hereditary progressive/dopa responsive dystonia caused
      by different types of mutations in the GTP cyclohydrolase I gene.
AB  - OBJECTIVE: Hereditary progressive dystonia with pronounced diurnal fluctuation
      [(HPD)/dopa responsive dystonia (DRD)] is a childhood onset dystonia which
      responds to levodopa. Various clinical signs and symptoms of HPD/DRD have been
      recognised to date. Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were
      recently identified as the cause of HPD/ DRD. In the present study, the GTP-CH-I
      gene and the clinical features of eight HPD/DRD patients from six families were
      analysed to determine the correlations between clinical expression and the
      mutations in the GTP-CH-I gene. METHODS: The exons, exon-intron junctions, and an
      indispensable part of the 5' flanking region of the GTP-CH-I gene were sequenced
      in the eight clinically diagnosed patients with HPD/DRD and their asymptomatic
      parents. RESULTS: Three independent mutations in the GTP-CH-I gene were found in
      three patients. One of the patients and her asymptomatic mother were heterozygous
      for a novel mutation at the initiation codon. The three patients with dissimilar
      GTP-CH-I mutations exhibited similar clinical features. The other five patients
      with normal sequences presented several features not manifested by the three
      patients with the mutations. No mutation was found in the 5' flanking region of
      any patients or their parents. CONCLUSIONS: A novel initiation codon mutation was
      found in a Japanese patient with HPD/DRD. The clinical manifestations common to
      the patients with HPD/ DRD with a mutated GTP-CH-I gene were also identified.
      Although focal manifestations of HPD/DRD associated with the mutations of this
      gene will be broadened, it is inferred that these clinical features are
      fundamental to HPD/DRD caused by mutations in this gene.

PMID- 9576538
TI  - Magnetic resonance angiographic and clinical features of extracranial vertebral
      artery dissection.
AB  - OBJECTIVES: Clinical data and neuroradiological findings of 19 patients with 20
      vertebral artery dissections were analysed to describe the features of time of
      flight magnetic resonance angiography (MRA) for the diagnosis and follow up of
      this vascular disorder. METHODS: All patients underwent a combined MRI and MRA
      protocol with 1.5 T scanners, using a three dimensional flow compensated gradient
      echo sequence for MRA. Duplex sonography was performed on all patients and
      selective angiography was available from 17 vertebral artery dissections.
      RESULTS: MRI showed ischaemic lesions of the brain in 18 of 19 patients (95%). In
      the acute and subacute stage, MRA detected signal abnormalities within the
      dissected vertebral artery in 94% (16/17) and MRI was specific for a dissection
      in 29% (5/17). Sensitivity of selective angiography was 100% and specificity was
      35% (6/17). Combination of the results of both methods increased the specificity
      to 50%. Duplex sonography was sensitive in 79% (15/19), but lacked specific
      results. Follow up magnetic resonance in 16 patients showed recanalisation of the
      dissected vessel in 10 (63%), persistent occlusion in five (31%), and a
      dissecting aneurysm in one (6%) patient. CONCLUSIONS: Magnetic resonance improves
      the triage for selective angiography and discloses complementary information for
      the diagnosis of vertebral artery dissection. If magnetic resonance identifies a
      double lumen or a mural haematoma with a stenosis or aneurysmal dilatation,
      invasive procedures can be omitted.

PMID- 9576539
TI  - Dysprosody after severe closed head injury: an acoustic analysis.
AB  - OBJECTIVES: Neurological speech disorders (dysarthria and dysprosody) are known
      to be frequent sequelae after severe closed head injury. These disorders may
      dramatically alter communicative intent and accentuate social isolation. The aim
      was to provide an instrumental evaluation for prosodic production in a group of
      patients with severe closed head injury and to determine the correlations between
      prosodic production and neurobehavioural status. METHODS: Fifteen patients, at
      the subacute stage after severe closed head injury, were studied and compared
      with 11 controls, matched for age, sex, and duration of education. Each subject
      was required to read aloud a French sentence "Je m'en vais samedi matin" (I am
      leaving saturday morning) under six different prosodic intonations (neutral,
      affirmation, interrogation, happiness, sadness, anger). The recorded sentences
      were analysed using a sound signal analysis software (Signalyse) allowing the
      measurement of signal intensity and fundamental frequency. Statistical analyses
      were carried out using repeated measures analysis of variance (ANOVA). RESULTS:
      Patients with closed head injury were significantly less able than controls to
      modulate speech output (pitch and intensity) according to prosodic context. This
      deficit was particularly pronounced for the intonation feature of anger,
      question, and statement. No consistent correlations could be found between
      prosodic production and cognitive or behavioural data. CONCLUSIONS: Acoustic
      analysis of pitch and intensity may show impairments of prosodic production after
      severe closed head injury, which may be useful in rehabilitation planning. This
      impairment does not seem to reflect the eventual cognitive and behavioural
      deficits of the patients, but rather a specific disorder of modulation of speech
      output.

PMID- 9576540
TI  - Interstitial glycerol as a marker for membrane phospholipid degradation in the
      acutely injured human brain.
AB  - OBJECTIVE: Brain interstitial glycerol was studied as a potential marker for
      membrane phospholipid degradation in acute human brain injury. METHODS: Glycerol
      was measured in microdialysis samples from the frontal lobe cortex in four
      patients in the neurointensive care unit, during the acute phase after severe
      aneurysmal subarachnoid haemorrhage. Microdialysis probes were inserted in
      conjunction with a ventriculostomy used for routine intracranial pressure
      monitoring. Clinical events involving hypoxia/ischaemia were diagnosed by
      neurological signs, neuroimaging (CT and PET), and neurochemical changes of the
      dialysate-for example, lactate/pyruvate ratios and hypoxanthine concentrations.
      RESULTS: Altogether 1554 chemical analyses on 518 microdialysis samples were
      performed. Clinical events involving secondary hypoxia/ischaemia were generally
      associated with pronounced increases (up to 15-fold) of the dialysate glycerol
      concentration. In a patient with a stable condition and no signs of secondary
      hypoxia/ischaemia the glycerol concentration remained low. Simultaneous
      determination of glycerol in arterial plasma samples showed that the changes in
      brain interstitial glycerol could not be attributed to systemic changes and an
      injured blood brain barrier. CONCLUSIONS: This study suggests that membrane
      phospholipid degradation occurs in human cerebral ischaemia. Interstitial
      glycerol harvested by microdialysis seems to be a promising tool for monitoring
      of membrane lipolysis in acute brain injury. The marker may be useful for studies
      on cell membrane injury mechanisms mediated by for example, Ca2+ disturbances,
      excitatory amino acids, and reactive oxygen species; and in the evaluation of new
      neuroprotective therapeutic strategies.

PMID- 9576541
TI  - Functional magnetic resonance imaging of human brain activity in a verbal fluency
      task.
AB  - OBJECTIVES: Functional MRI (fMRI) holds the promise of non-invasive mapping of
      human brain function in both health and disease. Yet its sensitivity and
      reliability for mapping higher cognitive function are still being determined.
      Using verbal fluency as a task, the objective was to ascertain the consistency of
      fMRI on a conventional scanner for determining the anatomic substrate of language
      between subjects and between sexes. Comparison was made with previous PET
      studies. METHODS: Using a 1.5 Tesla magnet and an echoplanar pulse sequence,
      whole brain fMRI was obtained from 12 normal right handed subjects (6 males and 6
      females) as they performed a verbal fluency task. RESULTS: A broadly consistent
      pattern of response was seen across subjects. Areas showing activation changes
      included the left prefrontal cortex and right cerebellum, in agreement with
      previous PET 15O-H2O studies. In addition, significantly decreased responses were
      seen in the posterior cingulate and over an extensive area of mesial and
      dorsolateral parietal and superior temporal cortices. The male cohort showed a
      slight asymmetry of parietal deactivation, with more involvement on the right,
      whereas the female cohort showed a small region of activation in the right
      orbitofrontal cortex. There were individual task related regional changes in all
      12 subjects with the area showing the most significant change being the left
      prefrontal cortex in all cases. CONCLUSIONS: Magnetic resonance scanners of
      conventional field strength can provide functional brain mapping data with a
      sensitivity at least that of PET. Activation was seen in left prefrontal and
      right cerebellar regions, as with PET. However, decremental responses were seen
      over a much larger area of the posterior cortex than had been anticipated by
      prior studies. The ability to see a response in each subject individually
      suggests that fMRI may be useful in the preinterventional mapping of pathological
      states, and offers a non-invasive alternative to the Wada test for assessment of
      hemispheric dominance. There were no gross differences in the pattern of
      activation between male and female subjects.

PMID- 9576542
TI  - Positron emission tomography in asymptomatic gene carriers of Machado-Joseph
      disease.
AB  - OBJECTIVES: The metabolic changes in the brain of symptomatic subjects affected
      with Machado-Joseph disease have been previously documented using PET with
      fluorine-18-fluorodeoxyglucose (FDG). The aim of this study was to evaluate these
      changes in asymptomatic Machado-Joseph disease gene carriers. METHODS: Seven
      asymptomatic Machado-Joseph disease gene carriers, identified using a molecular
      test, and 10 normal control subjects were recruited for PET studies using FDG.
      Regional uptake ratios of FDG were calculated from the radioactivity of the
      cerebellar hemispheres, brainstem, and the temporal, parietal and occipital
      cortices, divided by the activity in the thalamus. RESULTS: In comparison with
      data obtained from normal control subjects, there was significantly decreased FDG
      utilisation in the cerebellar hemispheres, brainstem, and occipital cortex, and
      increased FDG metabolism in the parietal and temporal cortices of asymptomatic
      Machado-Joseph disease gene carriers, suggesting preclinical disease activity.
      Discriminant analysis of regional FDG uptake correctly classified genetic status
      (Machado-Joseph disease mutation carriers v mutation negative subjects) in 25 of
      25 subjects (100% sensitivity and 100% specificity), and clinical status
      (asymptomatic mutation carriers v symptomatic patients) in 14 of 15 subjects
      (100% sensitivity and 85.7% specificity). CONCLUSION: Subclinical changes of FDG
      consumption, as measured by noninvasive PET, can act as an objective marker of
      preclinical disease activity in Machado-Joseph disease.

PMID- 9576543
TI  - Albrecht von Graefe (1828-70).

PMID- 9576544
TI  - Measurement of the retinal nerve fibre layer with scanning laser polarimetry in
      patients with previous demyelinating optic neuritis.
AB  - OBJECTIVES: Subjective visual deficits are common after demyelinating optic
      neuritis despite the frequent return of normal visual acuity. Visual and
      electrodiagnostic tests have demonstrated evidence of these persisting functional
      abnormalities, which are thought to be secondary to demyelination and variable
      axonal loss in the optic nerve. Scanning laser polarimetry (SLP) is a new image
      analysis technique which uses the polarising properties of the retinal nerve
      fibre layer (RNFL) to produce a quantitative measure of its thickness. This study
      was carried out to assess the prevalence, extent, and pattern of RNFL loss after
      demyelinating optic neuritis using SLP. METHODS: Twenty four patients with a
      history of previous demyelinating optic neuritis were re-examined. Examination
      included measurement of logmar visual acuity, Pelli-Robson contrast sensitivity,
      and the presence of a relative afferent pupil defect and optic atrophy. SLP was
      performed and a mean RNFL profile from a series of three images from each eye was
      constructed. This was compared with normative data from 20 age matched normal
      subjects. The lower 99.9% confidence limit of the normal data was calculated and
      used as the cut off criterion for abnormality. RESULTS: There were a total of 31
      eyes with a history of demyelinating optic neuritis and SLP disclosed an
      abnormality in 29 (94%) of these. Twenty three eyes recovered an acuity of 0.0 or
      better, 21 of which had evidence of RNFL loss on polarimetry. Scanning laser
      polarimetry was the only abnormality found in nine of the 31 eyes (29%). The
      pattern and extent of RNFL loss was very variable and there was no significant
      difference in these indices between patients with multiple sclerosis compared
      with those with isolated demyelinating optic neuritis. CONCLUSION: Scanning laser
      polarimetry can provide a quantitative measure of RNFL loss after demyelinating
      optic neuritis, demonstrating its occurrence in a high percentage of patients
      recovering normal visual acuity.

PMID- 9576545
TI  - Apathy and hypersomnia are common features of myotonic dystrophy.
AB  - OBJECTIVES: Myotonic dystrophy is a disease characterised by myotonia and muscle
      weakness. Psychiatric disorder and sleep problems have also been considered
      important features of the illness. This study investigated the extent to which
      apathy, major depression, and hypersomnolence were present. The objective was to
      clarify if the apathy reported anecdotally was a feature of CNS involvement or if
      this was attributable to major depression, hypersomnolence, or a consequence of
      chronic muscle weakness. METHODS: These features were studied in 36 adults with
      non-congenital myotonic dystrophy and 13 patients with Charcot-Marie-Tooth
      disease. By using patients with Charcot-Marie-Tooth disease as a comparison group
      the aim was to control for the disabling effects of having an inherited chronic
      neurological disease causing muscle weakness. Standardised assessment instruments
      were used wherever possible to facilitate comparison with other groups reported
      in the medical literature. RESULTS: There was no excess of major depression on
      cross sectional analysis in these patients with mild myotonic dystrophy. However,
      apathy was a prominent feature of myotonic dystrophy in comparison with a
      similarly disabled group of patients with Charcot-Marie-Tooth disease (clinician
      rated score; Mann Whitney U test, p=0.0005). Rates of hypersomnolence were
      greater in the myotonic dystrophy group, occurring in 39% of myotonic dystrophy
      patients, but there was no correlation with apathy. CONCLUSION: These data
      suggest that apathy and hypersomnia are independent and common features of
      myotonic dystrophy. Apathy cannot be accounted for by clinical depression or
      peripheral muscle weakness and is therefore likely to reflect CNS involvement.
      These features of the disease impair quality of life and may be treatable.

PMID- 9576548
TI  - Neuropsychological deficits in multiple sclerosis after acute relapse.
AB  - OBJECTIVES: To examine cognitive and neurological changes and their relation to
      brain pathology in patients with multiple sclerosis during acute relapse.
      METHODS: Thirteen patients with multiple sclerosis were examined with a battery
      of neuropsychological tests during acute relapse and six weeks later. Their
      performance was compared with the performance of 10 controls matched for age and
      premorbid IQ. Gadolinium (Gd) enhanced MRI was also performed in patients on both
      occasions. RESULTS: The patients with multiple sclerosis performed significantly
      worse than controls on most tests of attention and memory during acute relapse
      and in remission. At follow up there was a significant or trend of improvement in
      performance on some tests of attention for patients in whom the Gd enhanced
      lesion load had decreased. In this subgroup of patients, their improvement also
      correlated significantly with the reduction in acute lesion load. CONCLUSIONS:
      The findings suggest that certain neuropsychological deficits detected during an
      acute relapse may be reversible, particularly in patients who initially have mild
      cognitive impairment.

PMID- 9576549
TI  - Auditory hallucinations in Parkinson's disease.
AB  - Whereas visual hallucinations are often found among patients with Parkinson's
      disease, the occurrence of auditory hallucinations has never been systematically
      documented. The occurrence, past and present, of auditory hallucinations has been
      studied in 121 consecutive patients with Parkinson's disease attending a movement
      disorders clinic. The cognitive state was evaluated using the short mental test
      (SMT). Hallucinations were reported for 45 patients (37%); 35 (29%) had only
      visual hallucinations and 10 (8%) both visual and auditory hallucinations. No
      patient reported auditory hallucinations unaccompanied by visual hallucinations.
      The auditory hallucinations occurred repeatedly, consisting of human voices. They
      were non-imperative (n=9), non-paranoid (n=9), and often incomprehensible (n=5).
      They were not obviously influenced by the patients' age, duration of disease, or
      treatment with levodopa. Cognitive impairment was more common among hallucinating
      patients (64%, 50%, and 25% among patients with visual hallucinations, auditory
      hallucinations, and nonhallucinating parkinsonian patients respectively).
      Depression necessitating antidepressants was present in five of 10 and other
      psychotic features in six patients with auditory hallucinations. It is concluded
      that auditory hallucinations occur in Parkinson's disease, particularly in
      patients who also have visual hallucinations and are cognitively impaired.

PMID- 9576547
TI  - Akinetic mutism as a classification criterion for the diagnosis of Creutzfeldt
      Jakob disease.
AB  - OBJECTIVES: Among the classification criteria for the diagnosis of Creutzfeldt
      Jakob disease, akinetic mutism is described as a symptom which helps to establish
      the diagnosis as possible or probable. Akinetic mutism has been anatomically
      divided into two forms--the mesencephalic form and the frontal form. The aim of
      this study was to delimit the symptom of akinetic mutism in patients with
      Creutzfeldt-Jakob disease from the complex of symptoms of an apallic syndrome and
      to assign it to the individual forms. METHODS: Between April and December 1996,
      25 akinetic and mute patients with Creutzfeldt-Jakob disease were consecutively
      examined. The patients were classified according to the definition of akinetic
      mutism by Cairns and secondly in accordance with the features constituting the
      complete picture of an appalic syndrome (defined by Gerstenbrand). RESULTS: From
      25 patients with definite Creutzfeldt-Jakob disease, 24 patients showed
      impoverishment of speech and, after a mean duration of four (range 1.1-11.2)
      months, almost complete absence of voluntary movements and speech. Seven patients
      were classified as being mute and akinetic and assigned to the mesencephalic form
      whereas 13 patients were classified as apallic. One patient was mute without
      being akinetic and four patients were comatose. CONCLUSION: Diffuse brain damage
      underlies akinetic mutism in patients with Creutzfeldt-Jakob disease. The term
      can be used as a classification criterion for the diagnosis of Creutzfeldt-Jakob
      disease; however, it should be applied very carefully and delimited clearly from
      the apallic syndrome.

PMID- 9576546
TI  - Localised 1H-MR spectroscopy for metabolic characterisation of diffuse and focal
      brain lesions in patients infected with HIV.
AB  - OBJECTIVES: To evaluate the role of proton MR spectroscopy (1H-MRS) in detecting
      metabolic changes in diffuse or focal lesions in the brain of patients infected
      with HIV. METHODS: Sixty HIV seropositive patients (25 with HIV related
      encephalopathies, 20 with toxoplasmosis, eight with progressive multifocal
      leukoencephalopathies (PMLs), and seven with lymphomas) and 22 HIV seronegative
      neurological controls were examined with a combined MRI and 1H-MRS technique
      using a Siemens 1.5 Tesla Magnetom. Spectra (Spin Echo sequence, TE 135 ms) were
      acquired by single voxel, localised on focal lesions in toxoplasmosis, PML,
      lymphomas, and HIV encephalopathies and on the centrum semiovale of neurological
      controls. Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate, and
      lipids were evaluated in each spectrum and NAA/Cr, NAA/Cho, and Cho/Cr ratios
      were calculated. RESULTS: A significant decrease in NAA/Cr and NAA/Cho ratios
      were found in all HIV diagnostic groups in comparison with neurological controls
      (p<0.003), suggesting neuronal or axonal damage independent of brain lesion
      aetiology. However, the NAA/Cr ratio was significantly lower in PML and lymphomas
      than in HIV encephalopathies (p<0.02) and toxoplasmosis (p<0.05). HIV
      encephalopathies, lymphomas, and toxoplasmosis showed a significant increase in
      the Cho/Cr ratio in comparison with neurological controls (p<0.03) without
      between group differences. The presence of a lipid signal was more frequent in
      lymphomas (71%) than in other HIV groups (Fisher's test, p=0.00003). The presence
      of mobile lipid resonance together with a high Cho/Cr ratio in lymphomas may be
      related to an increased membrane synthesis and turnover in tumour cells. A
      lactate signal (marker of inflammatory reaction), was found in all but one
      patient with PML lesions (75%), but had a lower incidence in the other HIV
      diagnostic groups (Fisher's test, p=0.00024). CONCLUSION: 1H-MRS shows a high
      sensitivity in detecting brain involvement in HIV related diseases, but a poor
      specificity in differential diagnosis of HIV brain lesions. Nevertheless, the
      homogeneous metabolic pattern that characterises PML suggests the usefulness of
      1H-MRS as an adjunct to MRI in differentiating CNS white matter lesions, such as
      HIV encephalopathies, from PML.

PMID- 9576550
TI  - High frequency of unruptured intracranial aneurysms in female patients with
      ischaemic heart disease.
AB  - OBJECTIVES: Concurrence of coronary atherosclerotic lesions and intracranial
      aneurysms has been pointed out in several postmortem and clinical studies.
      However, the relative risk for intracranial aneurysms in patients with ischaemic
      heart disease remains uncertain. The aim of this study is to elucidate clinically
      whether ischaemic heart disease is a risk factor for intracranial aneurysms.
      METHODS: Between October 1993 and May 1995, 84 patients with ischaemic heart
      disease with angiographically established coronary artery stenoses who had no
      history of stroke (ischaemic heart disease group; men:women=58:26, mean (SD)
      age=61.1 (9.6) years) and 200 age matched subjects with minor neurological
      disorders who had no history of ischaemic heart disease (control group;
      men:women=117:83, mean (SD) age=62.0 (9.2) years) were screened with magnetic
      resonance angiography (MRA) for the presence of unruptured intracranial
      aneurysms. For all MRA positive patients, selective angiography was then
      undertaken. RESULTS: In the ischaemic heart disease group, the frequency of
      unruptured intracranial aneurysms established angiographically was 3.4% for men
      and 15.4% for women, compared with 2.6% and 3.6% respectively in the control
      group. Multiple logistic regression analyses disclosed that ischaemic heart
      disease was a significant and independent predictor for intracranial aneurysms in
      women. CONCLUSIONS: These results suggest that in women ischaemic heart disease
      is a risk factor for intracranial aneurysms. Coexistence of intracranial
      aneurysms should be suspected in women patients with ischaemic heart disease.

PMID- 9576551
TI  - Altered antibody pattern to Epstein-Barr virus but not to other herpesviruses in
      multiple sclerosis: a population based case-control study from western Norway.
AB  - OBJECTIVE: The prevalence of anti-EBV antibodies was studied in a group of 144
      patients with multiple sclerosis and 170 age, sex, and area matched controls from
      the county of Hordaland, western Norway. The prevalence of three other
      herpesviruses, herpes simplex virus (HSV), varicella zoster virus (VZV), and
      cytomegalovirus (CMV), were also included. METHODS: Antibodies to various virus
      antigens were determined by enzyme linked immunosorbent assay (ELISA) and
      indirect immunfluorescence (IIF) in serum samples from 144 patients with multiple
      sclerosis and 170 controls. RESULTS: All of the 144 patients with multiple
      sclerosis had IgG antibodies to EBV compared with 162 of 170 controls (p=0.008).
      The frequency of IgG antibodies to EBV capsid antigen (VCA), nuclear antigen
      (EBNA), and early antigen (EA) was significantly higher in patients with multiple
      sclerosis compared with the controls (p<0.000001, p=0.01, and p<0.0001
      respectively). The presence of antibodies was independent of the initial course
      of the disease and the disease activity at the time of blood sampling. The
      prevalence of IgG antibodies to HSV, CMV, and VZV did not differ between cases
      and controls. CONCLUSION: The results suggest a role for EBV in the aetiology of
      multiple sclerosis.

PMID- 9576552
TI  - A note on the origins of syphilis.

PMID- 9576553
TI  - Dominantly inherited proximal myotonic myopathy and leukoencephalopathy in a
      family with an incidental CLCN1 mutation.
AB  - A two generation family of Greek origin with mild myotonia, predominantly
      proximal muscle weakness, and cataracts compatible with the syndrome of proximal
      myotonic myopathy, is reported. In addition, brain MRI showed a diffuse
      leukoencephalopathy in the propositus. Molecular genetic studies showed the R894X
      mutation in exon 23 of the muscle chloride channel gene in the propositus but in
      only one of her two clinically affected offspring, indicating that it is not the
      mutation causing disease in this family.

PMID- 9576554
TI  - Presenilin 1 intronic polymorphism is not associated with Alzheimer type
      neuropathological changes or sporadic Alzheimer's disease.
AB  - BACKGROUND: A genetic association between the presenilin 1 (PS-1) intronic
      polymorphism and sporadic Alzheimer's disease has been a matter of controversy.
      Recent findings have suggested that the PS-1 polymorphism is not associated with
      Alzheimer's disease or amyloid beta-protein (Abeta) deposition in brains from
      patients with Alzheimer's disease. OBJECTIVES: To elucidate the influence of the
      PS-1 polymorphism on Alzheimer type neuropathological changes and the development
      of Alzheimer's disease, the relation between the PS-1 polymorphism and
      quantitative severity of Alzheimer type neuropathological changes in the brains
      from patients with Alzheimer's disease and non-demented subjects was studied.
      METHODS: The PS-1 and apolipoprotein E (ApoE) genotypes, were examined, together
      with the densities of the senile plaques, senile plaques with dystrophic
      neurites, and neurofibrillary tangles in the brains from 36 postmortem confirmed
      patients with sporadic Alzheimer's disease and 86 non-demented subjects.
      Association of the PS-1 polymorphism with sporadic Alzheimer's disease and ages
      at onset and duration of illness in Alzheimer's disease was also examined.
      RESULTS: The PS-1 polymorphism was not associated with the senile plaques, senile
      plaques with dystrophic neurites, or neurofibrillary tangles in Alzheimer's
      disease or non-demented subjects. There was no association of the PS-1 intronic
      polymorphism with Alzheimer's disease, ages at onset, or durations of illness in
      Alzheimer's disease. The results remained nonsignificant even when the PS-1
      genotype groups were divided into the subgroups with different ApoE epsilon4
      status. CONCLUSIONS: The PS-1 intronic polymorphism does not itself have a direct
      causal role in the formation of Alzheimer type neuropathological changes or in
      the development of sporadic Alzheimer's disease.

PMID- 9576555
TI  - Hypofunction in the posterior cingulate gyrus correlates with disorientation for
      time and place in Alzheimer's disease.
AB  - The relation between orientation for time and place and regional cerebral glucose
      metabolism was examined in 86 patients with probable Alzheimer's disease of
      minimal to moderate severity. Regional glucose metabolic rates in the posterior
      cingulate gyri and in the right middle temporal gyrus were significantly
      correlated with temporal orientation, and the glucose metabolic rate in the right
      posterior cingulate gyrus was significantly correlated with locational
      orientation irrespective of age, sex, education, and memory impairment. The
      results suggest that dysfunction of these structures plays an important part in
      producing disorientation in patients with Alzheimer's disease.

PMID- 9576556
TI  - Recovery from visuospatial neglect in stroke patients.
AB  - OBJECTIVES: To describe the natural recovery of visuospatial neglect in stroke
      patients and the distribution of errors made on cancellation tests using a
      standardised neuropsychological test battery. METHOD: A prospective study of
      acute (< seven days) patients with right hemispheric stroke. Patients identified
      with visuospatial neglect were followed up for three months with monthly clinical
      and neuropsychological testing RESULTS: There were 66 patients with acute right
      hemispheric stroke assessed of whom 27 (40.9%) had evidence of visuospatial
      neglect. Patients with neglect, on admission, had a mean behavioural inattention
      test (BIT) score of 56.3, range 10-126 (normal>129). Three of the subtests
      identified errors being made in both the right and left hemispaces. During follow
      up, recovery occurred across both hemispaces, maximal in the right hemispace.
      Recovery from visuospatial neglect was associated with improvement in function as
      assessed by the Barthel score. At the end of the study period only six (31.5%)
      patients had persisting evidence of neglect. On admission the best predictor of
      recovery of visuospatial neglect was the line cancellation test (Spearman's rank
      correlation r=-0.4217, p=0.028). CONCLUSION: The demonstration of errors in both
      hemispaces has implications for the theory that neglect is a lateralised
      attentional problem and is important to recognise in planning the rehabilitation
      of stroke patients.

PMID- 9576557
TI  - Posterior communicating artery aneurysm presenting with haemorrhage into an
      arachnoid cyst.
AB  - A patient is reported on with a subarachnoid haemorrhage (SAH) from an aneurysm
      of the posterior communicating artery, who initially presented with a sentinel
      bleed into an arachnoid cyst and normal magnetic resonance angiography (MRA) of
      the intracranial vasculature which led to a delay in diagnosis. Although this is
      a very rare presentation of a relatively common condition, it is important to
      recognise the importance of intracystic haemorrhage in such circumstances as well
      as the limitations of MRA, as a delay in diagnosis may have serious clinical
      consequences.

PMID- 9576558
TI  - Subacute autonomic and sensory ganglionopathy: a postmortem case.

PMID- 9576559
TI  - Intracranial calcification with IgG lambda M-proteinaemia: a case report.

PMID- 9576560
TI  - Subacute combined degeneration of the spinal cord after nitrous oxide
      anaesthesia: role of magnetic resonance imaging.

PMID- 9576562
TI  - Endovascular electroencephalography during an intracarotid amobarbital test with
      simultaneous recordings from 16 electrodes.

PMID- 9576561
TI  - Acute polyneuropathy with chronic lymphocytic leukaemia and paraproteinaemia:
      response to chlorambucil and prednisolone.

PMID- 9576563
TI  - Standardising care and clinical trials.

PMID- 9576564
TI  - Hepatic iron overload in the age of hereditary hemochromatosis mutation analysis.

PMID- 9576565
TI  - Hepatitis C virus and non-Hodgkin's lymphoma.

PMID- 9576566
TI  - Free prostate-specific antigen: does it measure up?

PMID- 9576567
TI  - Teaching the clinical interpretation of peripheral blood smears to a second-year
      medical school class using the PeripheralBlood-Tutor computer program.
AB  - The interpretation of peripheral blood smears has an important role in the
      diagnosis of hematologic diseases and is, therefore, part of the education of
      physicians and technologists. We describe a computer program, PeripheralBlood
      Tutor (Lippincott-Raven, Philadelphia, Pa), that teaches the morphologic features
      of normal and abnormal peripheral blood smears; we also describe the evaluation
      of the effectiveness of the program in 133 second-year medical students who were
      required to use the program in their hematology course. The version of the
      PeripheralBlood-Tutor used in the study had 2 distinct but equivalent 20-question
      examinations; one examination, the pretest, was taken before the students viewed
      the contents of the program, and the other examination, the posttest, was taken
      after completing the program. The mean score on the pretest was 61% (SD, 14%),
      the mean on the posttest was 91% (SD, 10%), and the improvement was significant.
      In addition, 4 questions about peripheral blood smears, which were based on
      printed images, were administered at the end of the hematology course. The
      students scored an average of 2.75 (SD, 0.86), and a positive correlation was
      found between these scores and the scores on the Tutor posttest. The results of
      the study suggest that PeripheralBlood-Tutor is feasible to implement, and it
      helps students learn to interpret peripheral blood smears. The use of
      PeripheralBlood-Tutor is now a requirement in the medical school curriculum, the
      medical technology program, and the pathology residency at the University of
      Washington, Seattle.

PMID- 9576568
TI  - Familial adenomatous polyposis: from bedside to benchside.
AB  - Familial adenomatous polyposis (FAP) is a dominantly inherited cancer
      predisposition syndrome with an incidence of between 1:17,000 and 1:5,000. The
      condition has been causally linked to mutation of the adenomatous polyposis coli
      (APC) gene located at 5q21. Virtually all mutations in the APC gene are
      truncating mutations, resulting in loss of function of the APC protein.
      Spontaneous germline mutation of this gene occurs frequently and accounts for the
      high incidence of FAP. The gene is somatically mutated at an early point in the
      colorectal adenoma-carcinoma progression. Somatic mutations of the APC gene are
      also frequently observed in a variety of other human carcinomas. Isolation of the
      APC gene has led to the recognition of genotype-phenotype correlations and,
      together with protein studies, has helped to elucidate the structure and function
      of the APC protein. This report aims to take the reader from a clinical
      appreciation to a molecular understanding of FAP.

PMID- 9576569
TI  - A rapid novel derivatization of amphetamine and methamphetamine using 2,2,2
      trichloroethyl chloroformate for gas chromatography electron ionization and
      chemical ionization mass spectrometric analysis.
AB  - Amphetamine and methamphetamine are commonly abused central nervous system
      stimulants. We describe a rapid new derivatization of amphetamine and
      methamphetamine using 2,2,2-trichloroethyl chloroformate for gas chromatography
      mass spectrometric analysis. Amphetamine and methamphetamine, along with N-propyl
      amphetamine (internal standard), were extracted from urine using 1-chlorobutane.
      The derivatization with 2,2,2-trichloroethyl chloroformate can be achieved at
      room temperature in 10 minutes. The electron ionization mass spectrum of
      amphetamine 2,2,2-trichloroethyl carbamate showed two weak molecular ions at m/z
      309 and 311, but showed diagnostic strong peaks at m/z 218, 220, and 222. In
      contrast, chemical ionization of the mass spectrum of amphetamine 2,2,2
      trichloroethyl carbamate showed strong (M + 1) ions at m/z 310 and 312 and other
      strong diagnostic peaks at m/z 274 and 276. The major advantages of this
      derivative are the presence of a diagnostic cluster of peaks due to the isotopic
      effect of three chlorine atoms (isotopes 35 and 37) in the derivatized molecule
      and the relative ease of its preparation. We also observed strong molecular ions
      for derivatized methamphetamine in the chemical ionization mass spectrum, but the
      molecular ions were very weak in the electron ionization mass spectrum. We used
      the scan mode of mass spectrometry in all analyses. When using a urine standard
      containing 1,000 ng/mL of amphetamine (a 7.4-micromol/L concentration) and
      methamphetamine (a 6.7-micromol/L concentration), the within-run precisions were
      4.8% for amphetamine and 3.6% for methamphetamine. The corresponding between-run
      precisions were 5.3% for amphetamine and 6.7% for methamphetamine. The assay was
      linear for amphetamine and methamphetamine concentrations of 250 to 5,000 ng/mL
      (amphetamine, 1.9-37.0 micromol/L; methamphetamine, 1.7-33.6 micromol/L). The
      detection limit was 100 ng/mL (amphetamine, 0.74 micromol/L; methamphetamine,
      0.67 micromol/L) using the scan mode of electron ionization mass spectrometry. We
      observed good a correlation between the concentrations of amphetamine and
      methamphetamine in five urine specimens positive for amphetamines using the more
      conventional pentafluoropropionyl derivative and our new derivative using 2,2,2
      trichloroethyl chloroformate.

PMID- 9576570
TI  - Serum percent-free PSA does not predict extraprostatic spread of prostate cancer.
AB  - Percent-free prostate-specific antigen (proportion of free prostate-specific
      antigen [PSA] to total PSA) has been shown recently in studies on frozen serum
      samples to be more useful than total PSA alone in distinguishing prostate cancer
      from benign conditions of the prostate gland. The primary purpose of our study
      was to determine whether percent-free PSA could predict extraprostatic spread of
      prostate cancer. We also sought to evaluate the freeze-thaw stability of free
      PSA. Percent-free PSA values in fresh serum samples were compared with those in
      aliquots subjected to one to five freeze-thaw cycles. Percent-free PSA values in
      frozen serum samples from 130 men undergoing radical prostatectomy for clinically
      localized prostate cancer were compared across pathologic stages. Free PSA levels
      remained stable for up to five freeze-thaws. Great overlap was found in percent
      free PSA values for men with organ-confined disease and those with extraprostatic
      spread. These results indicate that multiple freeze-thaw cycles do not
      significantly affect free PSA levels and percent-free PSA is not useful in
      identifying ideal candidates for radical prostatectomy.

PMID- 9576572
TI  - Evaluation of esophageal cytology using a neural net-based interactive scanning
      system (the PAPNET system): its possible role in screening for esophageal and
      gastric carcinoma.
AB  - A neural net-based, semiautomated, interactive computerized cell analysis system
      (The PAPNET system, Neuromedical Systems, Suffern, NY) was used to examine cells
      from 138 esophageal smears obtained by lavage, brushings, or balloon from as many
      patients. From each smear, trained human observers examined 128 cell images
      selected by the machine. Abnormal cells were identified in all 35 patients with
      cancer, whether esophageal, gastric, oral, or metastatic. Further, in 11 smears,
      the displayed images allowed the recognition of effects of radiotherapy and, in
      14 smears, the diagnosis of a specific tumor type, such as squamous cell
      carcinoma (8 patients) or adenocarcinoma (6 patients). In 3 additional cases, the
      diagnosis of "carcinoma, not further specified," was established. One case of
      esophageal carcinoma in situ, not previously recognized on a smear or in the
      biopsy specimen, and one case of gastric adenocarcinoma, not recognized in the
      smear, were identified in PAPNET-generated images. The possible application of
      the apparatus to the triage of smears and population screening for esophageal and
      gastric carcinoma precursors is discussed.

PMID- 9576571
TI  - Diagnostic value of brush cytology in the diagnosis of duodenal, biliary, and
      ampullary neoplasms.
AB  - Endoscopy is a valuable tool in the diagnosis and management of duodenal lesions
      and biliary strictures. We assessed the value of cytology in the evaluation of
      these lesions and analyzed the causes of discrepancy among clinical, histologic,
      and cytologic parameters. The study included 118 patients with duodenal ulcers,
      ampullary neoplasms, or biliary strictures who were examined between 1975 and
      1995; 120 cytologic examinations were performed. The specimens included brushings
      of the duodenum (DB, n = 50), ampulla (AB, n = 32), and biliary ducts (BB, n =
      38). Endoscopic biopsies performed concurrently included the duodenum (n = 37),
      the ampulla (n = 22), and the biliary ducts (n = 23). Comparison of cytologic and
      histologic results showed the following sensitivity and specificity: DB, 40% and
      97%, respectively; AB, 100% each; BB, 75% and 93%, respectively. The DB, AB, and
      BB revealed malignant neoplasms in 2 of 5, 7 of 7, and 6 of 8 cases,
      respectively. Twenty-three duodenal neoplasms were diagnosed by either modality
      and included 11 adenocarcinomas, 9 villous tumors, 2 metastatic renal cell
      carcinomas, and 1 large cell non-Hodgkin's lymphoma. Endoscopic brush cytology is
      an effective means of diagnosing ampullary neoplasms, and it complements tissue
      biopsy in cases of bile duct stricture. Location, predominance of tumor-induced
      stroma, an extramucosal growth pattern, sampling error, and interpretative
      experience influence the diagnostic evaluation. Cytologic diagnosis of an adenoma
      does not exclude an underlying malignant neoplasm in ampullary tumors. In some
      instances, it may be difficult to distinguish between villous tumors with severe
      dysplasia and adenocarcinomas by cytology alone.

PMID- 9576573
TI  - Histopathologic changes are not specific for diagnosis of gastric antral vascular
      ectasia (GAVE) syndrome: a review of the pathogenesis and a comparative image
      analysis morphometric study of GAVE syndrome and gastric hyperplastic polyps.
AB  - We studied the nonspecific nature of the histologic findings in the gastric
      antral vascular ectasia (GAVE) syndrome by using a morphometric comparison with
      common gastric lesions including hyperplastic polyps and gastritis. Five
      clinicopathologically confirmed cases of GAVE syndrome and 41 cases of gastric
      hyperplastic polyps were diagnosed during a 5-year interval at Summa Health
      Systems (Akron, Ohio). These cases, as well as 16 randomly selected cases of
      nonspecific gastritis and 9 normal gastric antral biopsy specimens, were
      evaluated. A semiquantitative comparison of the light microscopic findings
      believed to be essential in diagnosis of GAVE syndrome, including vascular
      hyperplasia, mucosal vascular ectasia, intravascular fibrin thrombi, and
      fibromuscular hyperplasia, was performed. Image analysis morphometric measures of
      the area ratio (vascular area/total biopsy area), mean vascular area, and number
      of ectatic vessels per square millimeter of tissue were performed on the CAS 200
      Image Analyzer (Becton Dickinson, San Jose, Calif). By morphometric and
      statistical parametric analysis, several histopathologic variables, including
      area ratio, mean vascular area, mucosal vascular ectasia, and fibromuscular
      hyperplasia, did not confidently differentiate the histologic features of gastric
      hyperplastic polyp from those of GAVE syndrome, but did apparently differentiate
      GAVE syndrome from gastritis and normal gastric mucosa. The propensity of gastric
      hyperplastic polyps to undergo prolapse changes and prolapse as one proposed
      mechanism for development of the GAVE syndrome lesion probably accounts for this
      morphologic similarity. Specific diagnostic histopathologic changes probably do
      not exist for the GAVE syndrome.

PMID- 9576574
TI  - Genetic changes associated with primary Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a malignant tumor of the skin with a well
      established neuroendocrine phenotype but an unknown histogenetic origin.
      Cytogenetic and molecular studies have shown evidence for genetic changes on the
      distal portion of chromosome 1p in different tumors with well-established
      neuroendocrine origins, specifically neuroblastomas, malignant melanomas, and
      pheochromocytomas. Involvement of chromosome 1 in MCC recently has been
      demonstrated by cytogenetic analysis and analysis of loss of heterozygosity (LOH)
      in metastatic tumor tissue. We performed analysis of LOH of the distal portion of
      chromosome 1p in paraffin material of 10 primary MCCs after tissue
      microdissection, using the polymorphic markers D1S160, D1S243, D1S468, D1S1646,
      and D1S1598. Seven of 10 analyzed MCCs shared a distal deletion involving 1p35
      36. None of the cases showed 1p involvement proximal to 1p35. The findings are
      similar to those described for malignant melanoma, pheochromocytoma, and
      neuroblastoma, tumors known to originate from neural crest cells. In conjunction
      with previous cytogenetic data, we conclude that Merkel cell carcinogenesis
      shares pathogenetic mechanisms with other neoplasms of neural crest derivation.

PMID- 9576575
TI  - A half a node or a whole node: a comparison of methods for submitting lymph
      nodes.
AB  - For many neoplasms, the status of regional lymph nodes is a critical prognostic
      factor with direct therapeutic implications. Despite the importance of lymph node
      status, there is no consensus on whether lymph nodes from node dissections should
      be submitted in their entirety. To study this issue, for a 4-month period, all
      lymph nodes from node dissections were submitted in their entirety. The larger
      nodes were submitted systematically to determine whether the additional tissue
      blocks contained metastases that were not identified in the initial tissue block.
      We also analyzed the cost of submitting, processing, and interpreting these extra
      blocks. During the study period, 149 patients underwent lymph node dissections,
      yielding a total of 2,915 lymph nodes. Submitting the larger nodes in their
      entirety resulted in processing 808 additional tissue blocks that demonstrated a
      total of 9 additional metastases in 7 patients. In 2 of these patients, the
      additional metastases changed the stage of the neoplasm and may have contributed
      to an alteration in therapy. By using median salary figures, the estimated cost
      for submitting, processing, and interpreting the additional blocks was $5,935.62.
      Whether the additional positive nodes justify this cost should be determined by
      individual pathology practices.

PMID- 9576576
TI  - Hepatic iron overload: direct HFE (HLA-H) mutation analysis vs quantitative iron
      assays for the diagnosis of hereditary hemochromatosis.
AB  - Among patients with hepatic iron overload, the distinction between hereditary
      hemochromatosis (HH), a common yet treatable genetic disease, and other causes of
      siderosis remains problematic. The recent discovery of a specific homozygous
      mutation (C282Y) in a novel major histocompatibility complex class I-like gene
      (named HLA-H or HFE) in 80% to 100% of well-characterized cases of HH suggests
      that direct DNA-based mutation analysis may help resolve this dilemma. To assess
      the clinical utility of direct HLA-H mutation analysis in a typical diagnostic
      setting, we measured genotypic and phenotypic parameters of iron overload in 37
      subjects with biopsy-proven hepatic siderosis (2+ or greater) and in 127 healthy
      control subjects. The prevalence of C282Y homozygotes was significantly greater
      in the hepatic siderosis group (32%) than in the control group (0%), confirming
      the association between this homozygous mutation and hepatic iron overload. In
      the hepatic siderosis group, C282Y homozygotes had significantly higher hepatic
      iron and ferritin levels, a significantly lower prevalence of hepatitis C virus
      or alcoholic liver disease, but no significant difference in the saturation of
      serum transferrin. Of the 20 subjects with a hepatic iron index (HII) in the
      previously defined "hemochromatosis range" (>1.9), 9 (45%) were C282Y
      homozygotes. Of the 11 nonhomozygous subjects with an HII greater than 1.9
      (presumed false-positive HIIs), 10 (91%) had hepatic cirrhosis compared with 3 of
      9 (33%) homozygotes with an HII greater than 1.9 who had cirrhosis (P<.02). The
      HII thus has poor diagnostic specificity for predicting genotypic HH in patients
      with cirrhosis. We conclude that direct determination of the HLA-H C282Y genotype
      may be the single best diagnostic test for HH, particularly in patients with
      cirrhosis, for whom the HII is quite nonspecific.

PMID- 9576577
TI  - Detection of oligoclonal bands in cerebrospinal fluid by immunofixation
      electrophoresis.
AB  - Multiple sclerosis is a severe demyelinating disease, the diagnosis of which is
      aided by biochemical tests, such as detection of oligoclonal immunoglobulin bands
      in the cerebrospinal fluid (CSF). Because interpretation of agarose gel
      electrophoresis (AGE) of CSF for oligoclonal bands is often equivocal, we
      compared immunofixation electrophoresis (IFE) with AGE for 124 consecutive CSF
      specimens submitted to the Parkland Memorial Hospital Clinical Chemistry
      Laboratory (Dallas, Tex) for detection of oligoclonal bands. Both methods used
      the Paragon Electrophoresis Systems (Beckman Instruments, Brea, Calif). Anti-IgG
      antisera was used exclusively on all specimens. Oligoclonal bands were identified
      in 23 specimens (18.5%), while the other 101 (81.5%) were interpreted as negative
      by both methods. Of the positive specimens, 17 (74%) were positive by both
      methods, 5 (22%) by IFE alone, and 1 (4%) by AGE alone. Of the 23 patients with
      positive specimens represented, 17 (74%) had been given a diagnosis of multiple
      sclerosis. The patient whose specimen was positive by AGE alone had a diagnosis
      of HIV infection with Guillain-Barre syndrome. The sensitivities (with 95%
      confidence intervals) of IFE and AGE were 73.9% (51.3-88.9) and 56.5% (34.9
      76.1), respectively. The specificities of both methods were identical at 95.0%
      (88.3-98.2). Subjective assessment of the gels demonstrated that the IFE method
      is consistently easier to interpret than AGE. The IFE method seems to be superior
      in identifying oligoclonal bands and thus aiding in diagnosis of demyelinating
      disorders.

PMID- 9576578
TI  - INR reporting in Canadian medical laboratories: an update. Thrombosis Interest
      Group of Canada.
AB  - A written survey of all licensed medical laboratories performing coagulation
      testing in Canada was undertaken in 1996 as a follow-up to a study performed in
      1992. The an overall response rate was 77.4% of the laboratories surveyed. During
      the 4-year period between surveys, the percentage of responding laboratories
      using some format for international normalized ratio (INR) reporting increased
      from 57% to 98%. The mean International Sensitivity Index (ISI) of the various
      thromboplastins used had decreased from 2.07 to 1.63. However, only 35% of
      responding laboratories used a thromboplastin with an ISI of 1.2 or less as
      recommended by the American College of Chest Physicians. In 92% of cases, the ISI
      was said to be specified for the type of instrument, ie, optical density vs
      mechanical. However, in only 52% of cases was the ISI known to be specific for
      the particular reagent-analyzer combination used in the individual laboratory.
      Nine percent of the laboratories were still using an inappropriate denominator
      for the INR calculation. While 87% of laboratories quoted a therapeutic INR range
      of 2.0 to 3.0 for venous thromboembolism, there was much greater variation in the
      range reported for patients undergoing heart valve replacement. The situation in
      Canada has improved in using the INR system for prothrombin time reporting.
      However, additional education is required, as is greater use of thromboplastins
      with a lower ISI.

PMID- 9576579
TI  - Minimum specimen volume requirements for routine coagulation testing: dependence
      on citrate concentration.
AB  - We evaluated the effect of sample volume and citrate concentration on results of
      routine coagulation assays (prothrombin time [PT] and activated partial
      thromboplastin time [APTT]). The study was performed on samples obtained from
      healthy persons and patients receiving oral anticoagulant therapy. Standard
      evacuated tubes (3.2% and 3.8% sodium citrate) were filled to varying total
      sample volumes ranging from 3.0 to 5.0 mL, and results of routine coagulation
      tests were compared. Underfilling may significantly affect the APTT and PT,
      resulting in artifactual prolongation of results. This effect is most pronounced
      in samples drawn into 3.8% citrate. By using 3.8% citrate, there is a
      statistically significant difference in the results of PT assays in the samples
      less than 80% filled compared with those that are 100% filled. For APTT assays
      performed on samples drawn into 3.8% citrate, a statistical difference occurred
      at less than 90% filled. This effect was less pronounced when samples were drawn
      into 3.2% sodium citrate. We found no statistically significant difference in PT
      results from a 3.2% citrate tube between fill volumes of 60% and 100% and none
      for APTT results between fill volumes of 70% and 100%. This study further
      supports the recommendation to use 3.2% sodium citrate concentration, because 60%
      of the optimum filled volume for PT and 70% of the optimum filled volume for APTT
      are acceptable.

PMID- 9576580
TI  - Extranodal lymphomas associated with hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma.
      We describe eight cases of B-cell extranodal non-Hodgkin's lymphoma occurring
      during the course of chronic HCV-related hepatic disease (low-grade of mucosa
      associated lymphoid tissue [MALT]-type; diffuse large cell; Burkitt; diffuse
      small cell). Some were localized to the liver (2), liver and spleen (1), spleen
      (1), peritoneal cavity (1), parotid gland (1); others manifested in the
      nasopharynx (1) and eyelid (1) but were accompanied by nodal disease. Four
      lymphomatous specimens available for molecular analysis exhibited clonal
      immunoglobulin gene rearrangements, lacked bcl-2, bcl-6, c-myc genes and p53
      alterations, and did not contain replicative intermediate HCV RNA, as documented
      by a strand-specific reverse transcriptase-polymerase chain reaction. Low levels
      of positive-strand HCV RNA were detected in a single hepatic lymphoma, suggesting
      the presence of the virus in residual hepatocytes. The antigen-driven properties
      of HCV-associated B-cell malignant neoplasms may be considered for hepatic MALT
      type lymphoma, which probably originated from lymphoid tissue acquired during
      long-standing HCV infection.

PMID- 9576581
TI  - T-cell subset analysis of peripheral T-cell lymphomas by paraffin section
      immunohistology and correlation of CD4/CD8 results with flow cytometry.
AB  - Peripheral T-cell lymphomas (PTCLs) are often diagnosed after demonstration of T
      lineage-related antigen expression on neoplastic lymphocytes by paraffin
      immunoperoxidase (PIP). However, complete T-cell subset analysis for helper,
      suppressor/cytotoxic, alphabeta, and gammadelta phenotypes has not been examined
      by PIP. Therefore, PIP was performed for CD4, CD8, T-cell intracellular antigen
      (TIA)-1, and betaF1 expression in 31 PTCLs previously studied for CD4 and CD8 by
      flow cytometry. The CD4 and CD8 results from both methods were compared. All
      betaF1- PTCLs were studied for T-cell receptor (TCR)gammadelta by PIP. PIP showed
      71% correlation with the 21 PTCLs that had distinct CD4+ CD8- or CD4- CD8+
      phenotypes by flow cytometry, with 64% and 90% sensitivity for CD4 and CD8
      expression, respectively. Tumor cells in four of six PTCLs that had no clear CD4
      or CD8 predominance or coexpression of these antigens by flow cytometry were
      shown to be CD4+ CD8- or CD4- CD8+ by PIP. Twelve (39%) PTCLs demonstrated a
      cytotoxic (TIA-1+) phenotype by PIP, including eight CD4- CD8+, one CD4+ CD8- and
      three CD4- CD8- cases. Of 30 immunoreactive PTCLs, 26 (87%) were alphabeta
      (betaF1+) by PIP. Both large cell cases among four betaF1- PTCLs were
      TCRgammadelta+ by PIP, including one gammadelta+ case confirmed by flow
      cytometry. We conclude that CD4 and CD8 T-cell subsets can be assigned for most
      PTCLs by PIP, with CD4 showing moderate and CD8 showing strong correlation with
      flow cytometric results. PIP can also define CD4 or CD8 expression on tumor cells
      in the PTCLs in which flow cytometry produces inconclusive results. Cytotoxic
      PTCLs can be identified easily with TIA-1, which can also distinguish cytotoxic
      from "suppressor" CD8+ PTCLs. Most PTCLs are derived from alphabeta T-cells,
      however some large cell gammadelta PTCLs may be identified by PIP.

PMID- 9576582
TI  - Hodgkin's disease in Costa Rica: a report of 40 cases analyzed for Epstein-Barr
      virus.
AB  - We studied 40 cases of Hodgkin's disease (HD) from Costa Rica for evidence of
      Epstein-Barr virus (EBV) in the Reed-Sternberg and Hodgkin (RS-H) cells. We also
      compared the epidemiologic features of these patients with previous reports of HD
      in industrialized and developing nations. Because Costa Ricans enjoy a relatively
      higher standard of living than the residents of other developing Central American
      nations yet live in the same general geographic region and are genetically
      similar, we believed that this comparison might shed additional light on the
      hypothesis that the prevalence of EBV in HD and the epidemiologic factors of HD
      are influenced by socioeconomic factors. In 16 (40%) of 40 cases,
      immunohistochemical studies demonstrated that the RS-H cells were positive for
      EBV latent membrane protein (LMP), including 1 case of lymphocytic depletion
      analyzed, 12 (86%) of 14 cases of mixed cellularity, and 3 (15%) of 20 cases of
      nodular sclerosis. All five cases of lymphocytic predominance were negative. In
      the 16 EBV LMP-positive cases, polymerase chain reaction studies revealed that
      the virus was type A in 12 cases and type B in 4 cases. Nodular sclerosis was the
      most common type of HD, accounting for 20 cases (50%), followed by mixed
      cellularity, with 14 cases (35%). The relatively low prevalence of EBV in the RS
      H cells of HD and the high incidence of nodular sclerosis in Costa Rica are
      similar to industrialized nations and are unlike HD in neighboring Central
      American countries. These findings further support the hypothesis that the
      prevalence of EBV in HD and the epidemiologic features of HD are most closely
      linked with socioeconomic conditions, and geographic location or ethnic heritage
      are of relatively less importance.

PMID- 9576583
TI  - Combining morphology and flow cytometric immunophenotyping to evaluate bone
      marrow specimens for B-cell malignant neoplasms.
AB  - For this study, 188 bone marrow core biopsy specimens and aspirates analyzed
      morphologically and by flow cytometric immunophenotyping (FCI) in patients with a
      previous or new diagnosis of B-cell non-Hodgkin's lymphoma or mature B-cell
      leukemia were retrospectively reviewed to evaluate patterns of involvement and
      the usefulness of FCI. The morphologic and FCI results were categorized as
      follows: positive by morphologic examination and by FCI (39.9%); negative by
      morphologic examination and by FCI (41.5%); positive by morphologic examination
      and negative by FCI (11.7%); negative by morphologic examination and positive by
      FCI (2.6%); suggestive of malignant neoplasm by morphologic examination and
      positive by FCI (2.1%); and suggestive of malignant neoplasm by morphologic
      examination and negative by FCI (2.1%). Thus, in 81.4% of cases the morphologic
      and FCI findings were completely concordant. In 11.7% of cases, the morphologic
      examination alone detected involvement, and in 4.7% of cases, the FCI data
      detected involvement in a morphologically negative or "suggestive" bone marrow
      core. Combining these modalities is essential to evaluate bone marrow specimens
      for involvement by B-cell non-Hodgkin's lymphoma or B-cell leukemia.

PMID- 9576584
TI  - Comparison of virus culture and direct immunofluorescent staining of
      cytocentrifuged virus transport medium for detection of varicella-zoster virus in
      skin lesions.
AB  - Direct immunofluorescent staining of centrifuged viral transport medium (CVTM)
      was compared with conventional cell culture for the detection of varicella-zoster
      virus (VZV) in 87 dermal lesions from 84 patients. A total of 21 (24%) were
      positive for VZV; 8 (38%) of these were positive by culture and CVTM, 13 (62%) by
      CVTM alone, and none by culture only. Virus cultures were positive for VZV in an
      average of 9.1 days (range, 4-20 days). CVTM, using cytocentrifugation, is more
      sensitive and rapid than conventional cell culture for the detection of VZV in
      cutaneous specimens.

PMID- 9576585
TI  - Comparison of two rapid latex agglutination tests for detection of cryptococcal
      capsular polysaccharide.
AB  - The Murex Cryptococcus Test was compared with the Cryptococcal Antigen Latex
      Agglutination System (CALAS) for detecting cryptococcal polysaccharide in 173
      cerebrospinal fluid (CSF) specimens and 117 serum samples with 99% and 97%
      concordance, respectively. Eighteen CSF samples and 17 serum samples were
      positive in both assays, and 249 were negative. The sensitivity and specificity
      of the Murex relative to the CALAS were 90% and 100%, respectively, for CSF, and
      81% and 100%, respectively, for serum. Six discrepancies were arbitrated by
      retesting, using a third analytic method, review of other laboratory and clinical
      data, or both. The reaction in 1 CSF specimen was considered false positive by
      the CALAS, and the reactions in 2 serum samples were false negatives by the
      Murex. For 3 patients with previous cryptococcal meningitis but no active
      disease, only the CALAS detected antigen, suggesting that the Murex has less
      analytic sensitivity in this context. Titer differences dictate that direct
      comparisons between the 2 tests are not feasible. There were no false-positive
      reactions in limited testing with either method using specimens from patients
      with concurrent noncryptococcal infections or in rheumatoid factor-positive serum
      samples. Infections caused by Cryptococcus neoformans serotypes A or AD were
      detected equally by both assays. Based on our study, we have elected to continue
      to use the CALAS for routine testing for cryptococcal antigen.

PMID- 9576586
TI  - Polymerase chain reaction assay for the detection and identification of
      Mycobacterium leprae in patients in the United States.
AB  - The differentiation of leprosy from other cutaneous granulomatous diseases is
      routinely based on characteristic histopathologic features and the demonstration
      of Mycobacterium leprae by acid-fast staining. Increased ascertainment of other
      mycobacterial infections in the skin has made this task more difficult, but the
      distinction remains fundamental for the selection of appropriate treatment.
      Experience with formalin-fixed, paraffin-embedded tissues, frozen tissues, and
      tissue lysates referred for detection of M. leprae DNA by a polymerase chain
      reaction (PCR) assay during the past 4 years was reviewed. This assay was done by
      using primers and probes previously developed in our laboratory to amplify a 360
      base-pair fragment of the gene for an 18-kD protein of M. leprae. Among biopsy
      samples obtained from 37 patients, PCR results were positive for 10 of 20 samples
      diagnosed as leprosy by histopathologic criteria and in 0 of 17 not diagnosed as
      leprosy. The specificity of the assay was 100% in this clinical referral
      material; sensitivity ranged from 50% to 83%. The PCR assay also identified M.
      leprae in one third of samples in which acid-fast organisms were seen and the
      histopathologic features were consistent with but not definitive of leprosy. In a
      nonendemic population, the sensitivity and specificity of PCR assay recommend its
      use primarily to identify M. leprae when acid-fast organisms are discernible but
      atypical clinical or histopathologic features obscure the diagnosis. The assay is
      not highly informative when acid-fast bacilli are not detectable by light
      microscopy.

PMID- 9576587
TI  - Leiomyosarcoma of the female breast.

PMID- 9576588
TI  - The effect of carbon tetrachloride on the detection of hemoglobin H using various
      commercially available electrophoresis products.

PMID- 9576589
TI  - A comparison between horizontal splint and repositioning splint in the treatment
      of 'disc dislocation with reduction'. Literature meta-analysis.
AB  - We reviewed the literature from 1985 to 1996 concerning the preliminary treatment
      of disc dislocation with reduction (DDWR) by means of occlusal splints,
      pinpointing two main methods. The conflicting results of many papers induced us
      to make a literature meta-analysis of those articles with the necessary
      requirements in order to verify the effectiveness of the two therapeutic means
      more frequently used in DDWR; the repositioning splint and the bite plane. A
      statistical comparison between the two kinds of treatment has demonstrated that
      the repositioning splint is more effective both in the resolution of the
      articular click and of the pain at a level of P < or = 0.00001, which is
      noteworthy and highly significant.

PMID- 9576590
TI  - Long-term strength of aesthetic restoratives.
AB  - Glass-ionomer cements have established an important role in clinical dentistry
      since their introduction over 20 years ago. More recently, in an attempt to
      enhance the strength of the material, resin additions have been made to
      conventional glass-ionomer cements. This study established the long term flexural
      strength of two hybrid glass-ionomer cements, by use of a bi-axial flexural
      strength test (Shell test), and compared the values with those obtained for a
      light curing composite resin and a conventional glass-ionomer cement. The results
      demonstrated that those materials with a high resin component relying on
      polymerization as the main method of setting had a greater initial flexural
      strength than those with little or no resin addition. Those materials where the
      glass-ionomer acid-base reaction provided a substantial contribution to the
      setting reaction showed an increase in strength as they matured, whereas a
      decline in strength with time was observed for those materials where the resin
      setting reaction predominated.

PMID- 9576591
TI  - Component release from light-activated glass ionomer and compomer cements.
AB  - The purpose of this study was to identify and quantify any component released
      from seven commercially available light-cured or resin-modified glass ionomer and
      compomer cements. Twenty-one separate cylindrical stainless steel moulds 6 mm in
      diameter and 1.0 mm deep were filled with one of seven glass ionomer or compomer
      cements, light activated and then immediately immersed in separate containers of
      distilled water. Water samples were retrieved over a time period of up to 30 days
      and retained for analysis. An occlusal cavity 6 mm in diameter was prepared in
      extracted human third molar teeth with a remaining dentin thickness of 1.6-2.0
      mm. A polypropylene chamber was attached to the cemento-enamel junction of each
      tooth to contain 1 mL of distilled water. Ten teeth were each filled with one of
      three cements and light activated. Water samples (eluates) were retrieved over a
      period of time. All samples were analysed by high performance liquid
      chromatography. Only one component, hydroxyethyl methacrylate (HEMA), was
      detected in the eluates from both tooth and mould samples. Analysis of diffusion
      of the HEMA through dentin showed a relatively sustained movement into the pulp
      space during the first day, with exponential decline thereafter. Our data show
      that HEMA was released from all of the light activated glass ionomer cements
      studied and from the compomer, both directly into water and through dentin. This
      release may be relevant both to the risk of adverse pulpal responses in patients
      and to the risk of allergy in patients and dental personnel.

PMID- 9576592
TI  - Some aspects of the tensile strength of undirectional glass fibre-polymethyl
      methacrylate composite used in dentures.
AB  - The aim of this study was to determine the tensile strength and E-modulus of
      unidirectional denture glass fibre-polymethyl methacrylate (GF-PMMA) composite
      with various fibre contents. The experimental values of tensile strength and E
      modulus were compared with values obtained by a theoretical calculation.
      Autopolymerized PMMA test specimens (n = 6, per group) were reinforced with
      unidirectional E-glass fibres which had been wetted in a mixture of PMMA powder
      and monomer liquid. After storing the test specimens for 40 days in water at 37
      degrees C, the tensile strength and E-modulus of the test specimens were
      measured. The increased amount of fibres in the PMMA matrix (up to 14.8% by
      weight) increased the mean tensile strength of the test specimens from 40.5 MPa
      to 91.2 MPa (P < 0.001) and the E-modulus from 2057 MPa to 3751 MPa (P < 0.001).
      The experimental tensile strength and Emodulus values were considerably lower
      than those based on the theoretical calculations. This was assumed to be due to
      the percentage of glass fibres unimpregnated with the PMMA resin. The presence of
      unimpregnated glass fibres was determined using light microscopy. The results of
      this study suggest that a new method of incorporating the glass fibres into the
      PMMA resin matrix should be developed in order to obtain a well-impregnated fibre
      composite reinforcement with high durability.

PMID- 9576593
TI  - The effect of dental alloys on mouse lymphocyte subpopulations.
AB  - The aim of the present study was to determine the effect of nickel-containing
      alloys on lymphocyte subsets in an experimental setting. Plates of alloys
      containing nickel (Ceramalloy, Talladium, Cerillium, Rexillium) or gold (Orion)
      were implanted subcutaneously into mice. The levels of CD4+ and CD8+ T-lymphocyte
      subpopulations and of Smig+ B lymphocytes were determined at various intervals
      following implantation, using monoclonal antibodies and flow cytometry. No
      changes were detected in the proportion of the lymphocyte subsets tested. One
      month after implantation, the mean fluorescence intensity of CD4, CD8 or Smig, in
      the peripheral blood lymphocytes (PBL) of the nickel alloy-implanted animals, was
      significantly higher than that prior to this procedure. Only a mild increase in
      CD4 and CD8 was noted after implantation of the gold alloy. The observed effects
      are most likely attributable to the surgical trauma, and do not indicate that
      nickel-containing dental alloys influence T cell subsets in this murine model.

PMID- 9576594
TI  - Analysis of residual ridges and ridge relationship by three-dimensional
      reconstruction method.
AB  - The purpose of this study was to develop a diagnostic system with which to
      determine the adequate area for artificial tooth arrangement on the posterior
      residual ridge. Edentulous plaster models and occlusion rims were measured by a
      non-contact type shape measurement system. Three trigonal pyramids and their
      impressions on the occlusion rims were used as landmarks for the analysis and
      superimposition of the analysis results for the upper and lower ridges. The data
      points were obtained at intervals of 0.5 mm in the lateral direction and of 0.25
      mm in the anteroposterior direction, and were interpolated by cubic spline curves
      in the lateral direction. When the ridge contour of the reconstructed image came
      in contact with the tangent line inclined at 30 degrees to the tentative plane of
      occlusion at the buccal and lingual sides in the frontal section, the area
      between their points of contact on both sides was comparatively flat and was
      regarded as adequate for the artificial posterior tooth arrangement in this
      study. This diagnostic system seems to be useful in determining the adequate area
      for the artificial tooth arrangement on the posterior residual ridges of
      edentulous plaster models and in displaying their horizontal relationship.

PMID- 9576595
TI  - Self-assessed masticatory ability in relation to maximal bite force and dental
      state in 80-year-old subjects.
AB  - By means of a questionnaire, clinical examination and force recordings, the
      relationships between self-assessed masticatory ability, dental state and bite
      force were studied in 160 80-year-old persons, 74 men and 86 women. The subjects
      were in general satisfied with their masticatory ability and 70% had no problems,
      while 6% reported three or more problems with mastication. Half of the subjects
      were dentate without removable prostheses and almost one-third had 20 or more
      natural teeth. The edentulous persons (about one-fifth of all) reported more
      problems related to mastication than the other dentition groups. The maximal bite
      force varied much and exhibited a significant correlation to the number of
      remaining teeth and dental state. The self-assessed masticatory ability was only
      weakly correlated with dental state and bite force. It was concluded that many
      subjects with few or no remaining teeth and/or removable dentures had only few
      complaints of impaired masticatory function and showed a good adaptation to an
      impaired dental status and small maximal bite force.

PMID- 9576596
TI  - In vitro adherence of Streptococcus constellatus to dense hydroxyapatite and
      titanium.
AB  - Bacterial adherence to dense hydroxyapatite (HA) and titanium (Ti) rods was
      examined in vitro using Streptococcus constellatus ATCC27832. Streptoccus
      constellatus is associated with dental abscess and was isolated from the peri
      implantitis. The dense HA was etched with 5% hydrofluoric acid for 0, 10, 20, 30,
      40, and 50 s Adherence to the untreated dense HA was twice as high as the
      adherence to the Ti. The adherence to saliva-treated Ti was 13% higher than that
      to untreated Ti. The adherence was increased by acid-treatment of the dense HA,
      following a sigmoid curve from 20 to 50 s of treatment time. The dense HA has the
      capacity to receive more bacterial adherence than Ti and furthermore, the etched
      dense HA becomes more adherent.

PMID- 9576597
TI  - Trigeminal responses evoked by painful electrical stimulation.
AB  - Trigeminal sensory and motor responses to high-intensity electrical stimuli were
      studied in 10 healthy male subjects. During contraction at 10% of maximal bite
      force, late exteroceptive suppression periods assessed by EMG and bite force from
      masseter muscles were recorded together with evoked vertex potentials. Electrical
      stimuli were either delivered as 1 ms single pulses or as 21 ms (5 x 1 ms, 200
      Hz) train pulses at two different intensities above the pain threshold. Three
      different perioral regions were stimulated in random order. The duration of the
      masseter suppression period was significantly longer and its latency
      significantly shorter at higher stimulus intensities whereas the amplitude of the
      evoked vertex potentials remained unchanged. Both the evoked potentials and the
      exteroceptive suppression period in the masseter muscle differed significantly
      between stimulation at the three perioral regions. The present results from
      combined measurements of sensory and motor responses in the trigeminal system may
      be explained by the function of trigeminal polysynaptic reflex circuits and the
      central cerebral processing of afferent inputs.

PMID- 9576598
TI  - In vivo and in vitro study of fungal presence and growth on three tissue
      conditioning materials on implant supported complete denture wearers.
AB  - In this study three type of tissue conditioning materials were used in vitro and
      in vivo to investigate the presence and growth of Candida albicans, considered to
      be the pathogenic member of the genus. In vitro test results of different tissue
      conditioners showed that they have a tendency to have an inhibiting effect on C.
      albicans at the third day of incubation. For the in vivo tests tissue
      conditioners were placed in existing maxillary prosthesis of 21 patients who had
      been treated with endosseous dental implants (seven in each group). The results
      showed that yeast forms were observed after 3 days in two patients' dentures
      which were relined with Fitt. Yeasts forms were also seen in three patients'
      dentures after 6 days, two of them relined with Fixo-gel and the other one
      relined with Visco-gel. The hyphal form of Candida was seen in four patients'
      dentures, relined with Fitt, and also in three patients' dentures, relined with
      Fixo-gel and Visco-gel.

PMID- 9576599
TI  - The analysis of frequency of occlusal sounds in patients with periodontal
      diseases and gnathic dysfunction.
AB  - A study is presented of occlusosonograms obtained from healthy subjects and
      patients with periodontal diseases and gnathic problems. Gnathosonic examinations
      were carried out by means of a set of equipment whose basic elements were two
      piezoceramic transducers mounted on a specially made holder and an IBM PC with an
      ADC card. The evaluation of occlusosonograms was by means of mathematical
      analysis of the frequency pattern. In pathological stages, the occlusosonograms
      exhibit more high frequency components. In the case of healthy subjects, the
      recorded signal took the form of a strong impact of low frequencies and its
      subsequent exponential decay.

PMID- 9576600
TI  - Lengths of condylar pathways measured with computerized axiography (CADIAX) and
      occlusal index in patients and volunteers.
AB  - The lengths of the condylar pathways during protrusive and opening movements were
      investigated with computerized axiography in 100 individuals. Forty-two patients
      suffering from anterior disk displacement with reduction (ADD) in one or both
      temporomandibular joints (TMJ) and 28 patients with anterior overrotation
      clicking (AOC) of the TMJ were compared with 30 asymptomatic volunteers. Patients
      suffering from ADD showed significantly shorter tracings than did the two other
      groups. A significant difference of length of TMJ movement between men and women
      was found only in one group. The occlusal indices (OI) of the three groups were
      assessed and compared with each other. Here, a significant difference was found
      between volunteers and patients suffering ADD and between volunteers and patients
      with AOC. Between men and women a significant difference of the OI was found in
      the group with AOC, women presenting higher scores than men. Except for the group
      of patients with ADD, who showed shorter average lengths, volunteers as well as
      patients with AOC, were within the normal limits given in the literature for TMJ
      movement lengths recorded with axiography. The results of this examination
      therefore indicate that when considering movement length alone no discrimination
      between healthy and diseased TMJ can be made.

PMID- 9576601
TI  - Speech intelligibility following maxillectomy with and without a prosthesis: an
      analysis of 54 cases.
AB  - To statistically evaluate the factors that influenced speech following
      maxillectomy, the speech intelligibility (SI) in 54 patients was measured with
      and without a prosthesis. The mean SI score without a prosthesis in all patients
      was 35.7 +/- 22.7% and that with a prosthesis was 84.9 +/- 12.7%. The results of
      the postmaxillectomy SI statistical analysis revealed that an oro-nasal
      communication was one of the factors that influenced SI without a prosthesis. The
      resection of the anterior portion of the soft palate was one of the factors that
      influenced SI with a prosthesis, which suggested that for some of these patients
      we should consider specific surgical treatment, aimed at the reconstruction in
      the deep defect extending to the intratemporal fossa. A new classification of
      maxillary defects has been proposed which will help to predict the grade of post
      maxillectomy speech disorder following surgery.

PMID- 9576602
TI  - Effects of a bite-raising splint on the duration of the chewing cycle and the EMG
      activities of masticatory muscles during chewing in freely moving rabbits.
AB  - Metal bite-raising splints of 0.5 mm thickness were attached to the upper molar
      teeth on both sides of the jaw in rabbits. The effects of these splints on
      masticatory behaviour during the chewing of soft food (bread) by freely moving
      rabbits were investigated. We recorded electromyograms (EMGs) of the masseter and
      digastric muscles. The animals exhibited prolongation of the chewing cycle,
      decreased EMG activity of the masseter muscle and increased EMG activity of the
      digastric muscle during chewing after introduction of the bite-raising splints.
      The effects of the splints on the activities of masticatory muscles were
      abolished by bilateral sectioning of the maxillary and inferior alveolar nerves.
      It seems likely that afferents from oral sensory receptors were responsible for
      the changes in masticatory behaviour after the introduction of the occlusal
      splint.

PMID- 9576603
TI  - Estrogen down-regulates mRNA encoding the exocytotic protein SNAP-25 in the rat
      pituitary gland.
AB  - Exocytosis is dependent on specific proteins that are located at the secretory
      granule membrane, in the cytoplasm or at the plasma membrane. The mRNA expression
      of synaptosomal-associated protein of 25 kDa (SNAP-25) isoforms SNAP-25a and SNAP
      25b, vesicle associated membrane protein (VAMP) 2, mammalian homologue of unc-18
      (munc-18) and Hrs-2 was studied in the pituitary of ovariectomized rats after
      subcutaneous insertion of capsules containing estrogen or placebo using in situ
      hybridization. Estrogen treatment (0.25 mg estradiol) significantly decreased
      SNAP-25a (32%; 10%) and SNAP-25b (25%; 22%) mRNA levels in the anterior and
      intermediate lobes, respectively, whereas VAMP-2, munc-18 and Hrs-2 mRNA levels
      remained unchanged. The results suggest that estrogen selectively regulates SNAP
      25 transcription in the pituitary gland, but leaves VAMP-2, munc-18 and Hrs-2
      mRNA levels unaffected.

PMID- 9576604
TI  - Multiple peptides infrequently coexist in progesterone receptor-containing
      neurons in the ventrolateral hypothalamic nucleus of the guinea-pig: an
      immunocytochemical triple-label analysis of somatostatin, neurotensin and
      substance P.
AB  - Progesterone plays an important role in regulating reproductive behaviour in
      guinea-pigs through actions exerted at the ventrolateral nucleus (VL), an area of
      the brain that contains progesterone receptors (PR) and neuroactive peptides,
      somatostatin (SOM), neurotensin (NT) and substance P (SP). Previous double-label
      analyses provided evidence that a substantial proportion of these
      neuropeptidergic cells contain PR. By means of triple-label immunofluorescence
      histochemistry, we examined whether PR are colocalized with two neuropeptides
      (SOM + NT or SP + SOM or SP + NT) within the same neurons in the VL.
      Ovariectomized guinea-pigs were primed with estradiol to induce PR
      immunoreactivity, and treated with colchicine to visualize immunoreactive (IR)
      neuropeptidergic cells. Both monoclonal mouse PR and polyclonal rabbit
      neuropeptide antibodies were used in double staining and in elution-restaining
      experiments. In the whole VL, the proportion of each coexisting peptide with PR
      obtained after double immunofluorescence appeared in decreasing order as: SOM
      (34%)>NT (25%)>SP (20%). Occasional colocalization was seen between PR and two
      neuropeptides throughout the rostrocaudal extent of the VL. Combining our various
      quantitative observations, we found that, of the total population of PR-IR
      neurons containing any combination of SOM, NT and SP, only about 1.5% contained
      SOM and NT, 2% contained SP and SOM and 1.6% contained SP and NT. These results
      indicate that while many PR-IR neurons also contain SOM or NT or SP in the guinea
      pig VL, there may be very few PR-IR neurons that express more than one of these
      three peptides.

PMID- 9576605
TI  - Dopamine-D2 actions on voltage-dependent calcium current and gonadotropin-II
      secretion in cultured goldfish gonadotrophs.
AB  - Dopamine D2-receptor activation directly inhibits GnRH-induced gonadotropin-II
      (maturational gonadotropin, GTH-II) secretion from goldfish pituitary cells. In
      this study, we show that dopamine and its D2 agonist, quinpirole, reduced GTH-II
      secretion induced by either high extracellular K+ concentration or the voltage
      gated Ca2+ channel agonist, Bay K 8644. These actions of dopamine were blocked by
      addition of the dopamine D2-receptor antagonist, spiperone. The actions of
      dopamine on Ca2+ current in single identified goldfish gonadotrophs were assessed
      in voltage-clamp experiments using Ba2+ as the charge carrier through voltage
      gated Ca2+ channels. Dopamine caused a concentration-dependent reduction in Ba2+
      current amplitude with an EC50 of 1.0+/-0.3 nM, but did not shift the current
      voltage relationship. The D2 agonist quinpirole also caused a dose-dependent
      reduction in the Ba2+ current amplitude with an EC50 of 2.7+/-1.4 nM. Quinpirole
      slowed the activation and inactivation kinetics, as well as removing the steady
      state inactivation properties of the Ba2+ current. In contrast to the actions of
      quinpirole, the dopamine D1-receptor agonist, SKF 38393, did not affect the Ba2+
      current. The inhibitory action of dopamine on voltage-dependent Ca2+ currents was
      reversed by spiperone, but not by the D1 antagonist SKF 83566. Voltage-dependent
      Na+ and K+ currents were not affected by dopamine or dopamine agonists. These
      data indicate that dopamine D2-receptor activation reduces Ca2+ influx through
      voltage-dependent Ca2+ channels to inhibit GTH-II secretion.

PMID- 9576606
TI  - Effects of the two somatostatin variants somatostatin-14 and [Pro2,
      Met13]somatostatin-14 on receptor binding, adenylyl cyclase activity and growth
      hormone release from the frog pituitary.
AB  - Two isoforms of somatostatin from frog brain have been recently characterized,
      namely somatostatin-14 (SS1) and [Pro2, Met13]somatostatin-14 (SS2). The genes
      encoding for the precursors of these two somatostatin variants are expressed in
      hypothalamic nuclei involved in the control of the frog pituitary. The aim of the
      present study was to investigate the effect of SS1 and SS2 on adenohypophysial
      cells. Autoradiographic studies using [125I-Tyr, D-Trp8] SS1 as a radioligand
      revealed that somatostatin binding sites are evenly distributed in the frog pars
      distalis. The SS2 variant was significantly (P < 0.01) more potent than SS1 in
      competing with the radioligand (IC50= 1.2 +/- 0.2 and 5.6 +/- 0.6 nM,
      respectively). Both SS1 and SS2 induced a modest but significant reduction in
      cAMP formation in dispersed distal lobe cells but did not affect spontaneous
      growth hormone (GH) release. Synthetic human GRF (hGRF) induced a significant
      increase in cAMP accumulation and GH release in this system. Both SS1 and SS2
      inhibited the stimulatory effects of hGRF on cAMP formation and GH secretion.
      These data show that the SS1 and SS2 variants can regulate adenohypophysial
      functions. The fact that GH cells are exclusively located in the dorsal area of
      the frog adenohypophysis, while somatostatin receptors are present throughout the
      pars distalis, indicates that the two somatostatin isoforms may control the
      secretion of pituitary hormones additional to GH in amphibians.

PMID- 9576607
TI  - Influence of adrenal glands on the modulation of prolactin gene expression by the
      endogenous benzodiazepine ligand octadecaneuropeptide in the male rat pituitary
      gland.
AB  - Recently, an 86-amino acid polypeptide with high affinity for diazepam binding
      sites, termed diazepam-binding inhibitor (DBI), has been found in the rat brain.
      DBI, as well as a peptide derived from DBI, the octadecaneuropeptide DBI[33-50]
      (ODN), interacts with the GABA(A) receptor complex. To investigate the role of
      these endogenous ligands for GABA(A) receptors on prolactin gene expression, we
      studied the effects of acute intracerebroventricular administration (4 h before
      sacrifice) of ODN on prolactin mRNA levels in the male rat. Because, in some
      neuropeptidergic systems, glucocorticoids play a role in the response to ODN, we
      also studied the influence of adrenal glands and the effect of dexamethasone
      administration in the response of prolactin gene expression to ODN. ODN injection
      produced an increase in prolactin mRNA levels. Adrenalectomy performed 5 days
      before sacrifice resulted in an increase in prolactin gene expression and also
      potentiated the stimulating effect of ODN. Because castration has been shown to
      decrease prolactin gene expression in the male rat, we used castrated and
      adrenalectomized animals to study the role of dexamethasone in the response of
      lactotrophs to ODN. In these steroid-deprived animals, dexamethasone treatment
      (for 4 days) decreased prolactin mRNA levels but did not modify the response to
      ODN. These data indicate that an endogenous neuropeptide interacting with the
      GABA(A) receptor complex can stimulate prolactin gene expression and suggest that
      the adrenal glands may produce factor(s) capable of decreasing prolactin mRNA. On
      the other hand, it does not appear that glucocorticoid hormones play a role in
      the effect of ODN on lactotroph activity.

PMID- 9576608
TI  - Multiple hypothalamic factors regulate pyroglutamyl peptidase II in cultures of
      adenohypophyseal cells: role of the cAMP pathway.
AB  - In the adenohypophysis, thyrotrophin-releasing hormone (TRH) is inactivated by
      pyroglutamyl peptidase II (PPII), a TRH-specific ectoenzyme localized in
      lactotrophs. TRH slowly downregulates surface PPII activity in adenohypophyseal
      cell cultures. Protein kinase C (PKC) activation mimics this effect. We tested
      the hypothesis that other hypothalamic factors controlling prolactin secretion
      could also regulate PPII activity in adenohypophyseal cell cultures. Incubation
      for 16 h with pituitary adenylate cyclase activator peptide 38 (PACAP; 10(-6) M)
      decreased PPII activity. Bromocryptine (10(-8) M), a D2 dopamine receptor
      agonist, or somatostatin (10(-6) M) stimulated enzyme activity and blocked the
      inhibitory effect of [3-Me-His2]-TRH, a TRH receptor agonist. Bromocryptine and
      somatostatin actions were suppressed by preincubation with pertussis toxin (400
      ng ml(-1)). Because these hypophysiotropic factors transduce some of their
      effects using the cAMP pathway, we analysed its role on PPII regulation. Cholera
      toxin (400 ng ml(-1)) inhibited PPII activity. Forskolin (10(-6) M) caused a time
      dependent decrease in PPII activity, with maximal inhibition at 12-16 h
      treatment; ED50 was 10(-7) M. 3-isobutyl-1-methylxanthine or dibutiryl cAMP,
      caused a dose-dependent inhibition of PPII activity. These data suggest that
      increased cAMP down-regulates PPII activity. The effect of PACAP was blocked by
      preincubation with H89 (10(-6) M), a protein kinase A inhibitor, suggesting that
      the cAMP pathway mediates some of the effects of PACAP. Maximal effects of
      forskolin and 12-O-tetradecanoylphorbol 13-acetate were additive. PPII activity,
      therefore, is independently regulated by the cAMP and PKC pathways. Because most
      treatments inhibited PPII mRNA levels similarly to PPII activity, an important
      level of control of PPII activity by these factors may be at the mRNA level. We
      suggest that PPII is subject to 'homologous' and 'heterologous' regulation by
      elements of the multifactorial system that controls prolactin secretion.

PMID- 9576609
TI  - Anterior pituitary cell population control: basal cell turnover and the effects
      of adrenalectomy and dexamethasone treatment.
AB  - We have used an extremely accurate, dedicated, real time computerized image
      analysis system to facilitate the manual quantification of changes in the
      prevalence of mitotic figures and apoptotic bodies in male rat pituitary
      following surgical adrenalectomy and, 14 days later, dexamethasone treatment.
      Under basal conditions, the prevalence of mitotic figures and apoptotic bodies
      was 0.066+/-0.016% and 0.030+/-0.012% (mean+/-SE) respectively. Dexamethasone
      treatment reduced the prevalence of mitotic figures and, in adrenalectomized
      animals, produced a highly significant and reproducible burst of apoptotic
      activity that peaked 48 h after the beginning of treatment (0.261+/-0.022%)
      before falling sharply to control levels within a further 8 h. Two weeks after
      the start of dexamethasone treatment, total pituitary cell numbers continued to
      decline. The rate of accumulation of mitotic figures in vivo after colchicine
      treatment indicates that mitosis is histologically overt in 2 microm thick
      hematoxylin and eosin stained sections under the light microscope for around 80
      min; that apoptosis--identified as classical apoptotic bodies--is overt for 44
      min and that, on average, a young, adult, male rat anterior pituitary cell either
      dies or divides as frequently as once every 60-70 days. These data show that
      transient and apparently trivial fluctuations in the prevalence of apoptotic and
      mitotic events have a profound effect on pituitary cell population dynamics, and
      demonstrate that dexamethasone treatment of adrenalectomized rats produces a
      decline in total anterior pituitary cell numbers that continues for at least 2
      weeks after the start of glucocorticoid treatment.

PMID- 9576610
TI  - Stimulation of Ca2+ entry in lactotrophs and somatotrophs from immature rat
      pituitary by N-terminal fragments of proopiomelanocortin.
AB  - We have previously shown that 10-12 kDa N-terminal fragments of rat
      proopiomelanocortin (POMC) and human POMC1-76 stimulate mitosis and/or
      differentiation in lactotrophs of early postnatal rat pituitary. A truncated
      form, POMC1-26, mimics the differentiation-inducing but not the mitogenic action
      of the former peptides. To further characterize these two biological responses,
      the present study compared changes in the intracellular free calcium
      concentration ([Ca2+]i) in response to POMC1-76 and POMC1-26 in isolated
      pituitary cells from 14-day-old female rats. Calcium (Ca2+) responses were also
      used as a guide to determine whether the responsive cells belong to the
      lactosomatotroph lineage. Application of POMC1-76 or POMC1-26 induced a
      maintained oscillating [Ca2+]i increase in a small population of cells.
      Increasing doses of the peptides did not affect the magnitude and the frequency
      of [Ca2+]i oscillations but clearly augmented the number of responding cells.
      Approximately 2% of the cells responded at 0.1 nM POMC1-76 or 5 nM POMC1-26, and
      11-13% of the cells responded at 10 nM and 500 nM of the respective peptides.
      About one-third of the cells responsive to these peptides also showed a [Ca2+]i
      increase in response to growth hormone-releasing peptide-6 (GHRP-6) while, in a
      small number of responsive cells, [Ca2+]i was depressed by dopamine, suggesting
      that the former cells are somatotrophs and the latter lactotrophs. This
      interpretation was confirmed by immunocytochemical identification of prolactin
      and growth hormone (GH) in the cells. Of the cells showing Ca2+ response to POMC1
      76, approximately one-third contained GH and another third prolactin. The
      remainder contained neither GH nor prolactin. Comparable results were obtained
      with POMC1-26. The rise of [Ca2+]i induced by the N-terminal POMC peptides
      persisted after depletion of intracellular Ca2+ stores by thapsigargin. Removal
      of Ca2+ from the extracellular medium or addition of cadmium completely abolished
      both the POMC1-76- and POMC1-26-induced [Ca2+]i increase. Nifedipine inhibited
      the Ca2+ response to both peptides, although only in 55% of the responsive cells.
      Depletion of some isoforms of protein kinase C by preincubation with the phorbol
      ester PMA for 24 h did not modify the Ca2+ responses. In contrast, blockade of
      the protein kinase A pathway with Rp-cAMPs partially inhibited the POMC1-76- or
      POMC1-26-induced [Ca2+]i increase. The present data show that, in immature
      pituitary cells, POMC1-76 induces an increase in [Ca2+]i through extracellular
      Ca2+ influx, possibly mediated in part by protein kinase A activation. The active
      domain of POMC1-76 seems to comprise its N-terminal moiety. The data support the
      hypothesis that POMC1-76 exerts a specific function in the development of
      different members of the lactosomatotroph lineage and that the peptide mobilizes
      different subsets of cells within this lineage, by a mechanism determined by its
      concentration.

PMID- 9576611
TI  - Electrochemical stimulation of the median eminence evokes FSH but not LH release
      after LHRH antagonist treatment in vivo and in vitro.
AB  - Experimental data suggest that a follicle stimulating hormone-releasing factor
      (FSH-RF) distinct from luteinizing hormone-releasing hormone (LHRH) exists. In
      the present study, we investigated, in short-term ovariectomized (OVX) rats,
      whether FSH-RF(s) can be released from nerve terminals by electrochemical
      stimulation (ECS) of the median eminence. To prevent the effect of LHRH liberated
      by ECS, 100 microg of a potent LHRH antagonist (MI-1544) was administered to one
      group of OVX rats 60 min before ECS. Two groups of OVX rats were used as
      controls. One group was treated with the solvent of the LHRH antagonist 60 min
      before the ECS; the other group received sham-ECS only. In-vitro experiments
      using a hypothalamus-pituitary coperifusion system were also performed to
      investigate the direct effect of ECS of the median eminence on LH and FSH release
      from pituitary cells. ECS in vivo induced 4.6-fold (P<0.01) and 10.2-fold
      (P<0.01) elevation of serum LH concentration, measured by RIA at 10 min and 60
      min after ECS, respectively. Serum FSH concentrations increased 1.35-fold at 10
      min (P<0.01) and 1.50-fold at 60 min (P<0.01) after ECS, compared with sham
      stimulated controls. Administration of LHRH antagonist attenuated the ECS-induced
      release of LH by 44% at 10 min and prevented it entirely at 60 min after ECS.
      However, the ECS-induced release of FSH was not modified by the antagonist at 10
      min and was diminished by only 17% at 60 min after ECS, compared with solvent
      treated and stimulated controls. Immunohistological examination of the
      hypothalami showed that LHRH-immunoreactivity was depleted in the region of ECS.
      In the study in vitro, substances released from the fragments of mediobasal
      hypothalami bearing ECS in the median eminence induced significant release of
      both LH and FSH, and the induced release of LH, but not FSH, was prevented by the
      LHRH antagonist. The present study suggests that FSH-releasing factor(s)
      different from LHRH can be released from the median eminence and that a
      significant portion of FSH secretion is independent of the control of LHRH.

PMID- 9576612
TI  - Regulation of T cell immunity and tolerance in vivo by CD4.
AB  - Previous experiments showed that peptides corresponding to a major CD4-binding
      site on the beta2 domain of MHC class II molecules, IAbeta134-148, enhance
      responses by CD4+ T lymphocytes to antigen, allo-antigen and bacterial
      superantigen in vitro, and to soluble protein in vivo. To determine whether
      peptide IAbeta134-148 acted by inhibiting antigen-induced T cell tolerance,
      ovalbumin-specific CD4+ lymph node (LN) T cells from TCR transgenic DO.11.10 mice
      were adoptively transferred into H-2 syngeneic BALB/c recipients. Tolerance was
      then induced by injecting antigen i.v. When peptide IAbeta134-148 was used to
      interfere with CD4-MHC class II interactions, accumulation of clonotype-positive
      T lymphocytes in the LN and induction of T cell tolerance in vivo were delayed.
      The mechanism by which peptide IAbeta134-148 inhibited T cell tolerance included
      the peptide's ability to block activation-induced cell death. Further, antigen
      specific splenic T lymphocytes were not tolerized in IAbeta134-148-treated mice,
      providing a reservoir of T cells that could respond to a secondary immunization.
      The results reported here suggest that participation of the T cell co-receptor,
      CD4, in TCR signaling differentially affected both T cell migration and the
      induction of antigen-specific tolerance. Therefore, in this in vivo model system,
      the combined strength of all signals received (e.g. via TCR, co-receptors and co
      stimulators) determined whether T cell immunity or apoptosis and tolerance
      resulted from antigenic stimulation. These findings are potentially important for
      the development of reagents to enhance vaccine efficacy and tumor immunity.

PMID- 9576613
TI  - Relationship between peptide binding and T cell epitope selection: a study with
      subtypes of HLA-B27.
AB  - The effect of HLA-B27 polymorphism on antigen presentation was analysed by
      comparing the binding of three Epstein-Barr virus-derived peptide epitopes to HLA
      B27 subtypes with their immunogenicity and antigenicity in the context of these
      subtypes. The effect of altering the major anchor residue Arg2 on binding or on
      recognition by peptide-specific cytotoxic T lymphocytes (CTL) was also examined.
      The three peptides bound significantly to all the B*2701-B*2706 subtypes. This
      did not correlate with the peptides being immunogenic or recognized by specific
      CTL in the context of only particular subtypes. In addition, of the three viral
      epitopes tested, those that were immunogenic in B*2702- or B*2705-restricted
      responses bound to these subtypes less efficiently than one peptide that was
      immunogenic only in the B*2704 context. Thus, among several potentially
      immunogenic peptides from the same virus, the antiviral response is not
      necessarily directed against the one that binds best to the restricting subtype.
      These results indicate that HLA-B27 polymorphism influences antigen presentation
      in ways other than simply peptide affinity. Synthetic analogues lacking the
      canonical Arg2 motif of HLA-B27-bound peptides, even when binding much worse to
      the restricting subtype, were recognized equally by CTL specific for the parental
      peptide. This indicates that Arg2 is not required to maintain the structure of
      the epitope. The implications of these results for pathogenetic models of HLA-B27
      associated disease are discussed.

PMID- 9576614
TI  - Myoblasts produce IL-6 in response to inflammatory stimuli.
AB  - Muscle fibers are the target of T cell-mediated cytotoxic reactions in
      polymyositis and inclusion body myositis, while the success of myoblast
      transplantation depends on the absence of an immune rejection against the
      myofibers. In order to study the behaviour of muscle cells in an inflammatory
      milieu, we investigated the production of IL-6 and its modulation, including the
      second messenger pathways controlling it, in in vitro highly purified human
      myoblast cultures. We found that IL-1beta, tumor necrosis factor (TNF)-alpha and
      lipopolysaccharide (LPS) stimulated myoblast IL-6 secretion in a dose- and time
      dependent manner, whereas forskolin and cholera toxin did not. HA1004 at 10
      microM did not significantly affect the IL-1beta- and TNF-alpha-induced IL-6
      secretion, suggesting that cAMP and protein kinase A are not sufficient to
      stimulate this process. To investigate the role of protein kinase C (PKC) in this
      signal transduction, we employed the inhibitor calphostin C, and the activators
      phorbol-12-myristate-13-acetate (PMA) and calcium ionophore A23187. Calphostin C
      blocked IL-6 secretion, PMA had a small stimulatory effect and A23187 had no
      effect; moreover, PKC down-regulation by PMA did not inhibit IL-1beta
      stimulation, while it reduced TNF-alpha stimulation. These data indicate that
      different PKC isoforms may be involved in TNF-alpha and IL-1beta signal
      transduction. Such a difference can distinguish the action of two traditionally
      'overlapping' inflammatory cytokines. Our data suggest that muscle cells, like
      myoblasts, satellite cells and in vivo regenerating myofibers, may discriminate
      between different stimuli and produce IL-6 when activated in response to muscle
      injury.

PMID- 9576615
TI  - Cloning and characterization of the guinea pig C5a anaphylatoxin receptor:
      interspecies diversity among the C5a receptors.
AB  - The anaphylatoxin C5a receptor (C5aR, CD88 in man) plays a prominent role in
      mediating inflammatory and host defense processes. Direct evidence of C5aR
      involvement in host defense mechanisms was demonstrated recently using C5aR
      knockout mice. Mice deficient in C5aR were unable to clear intrapulmonary
      instilled bacteria. The guinea pig system is perhaps unique for exhibiting cross
      reactivity with human complement components and its high sensitivity to
      anaphylatoxins. Therefore, we cloned the guinea pig C5aR from a megakaryocyte
      cDNA library. The deduced amino acid sequence of guinea pig C5aR is 67% identical
      to human, 61.6% to dog, 60.2% to mouse and 63.6% to rat C5aR. Transient
      expression of guinea pig C5aR in COS-7 cells and stable expression on L cell
      fibroblasts were confirmed by FACS analysis. Competitive binding studies using
      [125I]C5a and stimulation of calcium mobilization by C5a proved that functional
      C5aR was expressed on these stably transfected L cells. The N-terminal
      extracellular region of guinea pig C5aR was five to seven residues shorter than
      the same region in C5aR from other species and sequence homology was limited to
      11%. Other outer membrane loops were also poorly conserved (8-33%) when compared
      across five species. Transmembrane segments were highly conserved between these
      various species (46-86%). Guinea pig C5aR binds human C5a, therefore residues
      critical for C5a binding have been conserved between these species. Sequence
      comparison of C5aR from multiple species permits conserved elements of the ligand
      binding sites to be elucidated.

PMID- 9576616
TI  - Receptor-specific induction of NF-kappaB components in primary B cells.
AB  - The NF-kappaB transcription factor complex plays a key role in the expression of
      genes involved in immune responses. Nuclear NF-kappaB is induced in B lymphocytes
      by engagement of either the antigen receptor (sIg) or the CD40 receptor for a T
      cell activation antigen, although different intracellular pathways appear to be
      involved. In the present study the protein composition of NF-kappaB complexes
      triggered by sIg and CD40 was probed by electrophoretic mobility shift,
      supershift, shift-Western, and Western blot analyses. At the time of peak NF
      kappaB induction (2 h), the NF-kappaB components detected in the complexes
      induced through sIg and through CD40 were the same. However, with continued
      stimulation RelB completely disappeared from anti-Ig-stimulated kappaB binding
      material, but remained a component of CD40L-induced NF-kappaB. The loss of DNA
      binding RelB from anti-Ig-induced NF-kappaB did not result from depletion of RelB
      from B cell nuclei, suggesting specific regulation of RelB function which is not
      directly attributed to IkappaB function. These results indicate that NF-kappaB
      complexes may undergo protein-specific alterations in a time- and receptor
      dependent fashion that may be associated with differences in the outcomes of B
      cell stimulation through sIg and CD40.

PMID- 9576617
TI  - The immune response induced in vivo by dendritic cells is dependent on B7-1 or B7
      2, but the inhibition of both signals does not lead to tolerance.
AB  - Dendritic cells (DC) can be used as physiological adjuvant in vivo. Indeed, a
      single injection of DC, pulsed in vitro with antigen, induces activation of
      specific T and B lymphocytes in syngeneic mice. The unique capacity of DC to
      sensitize naive T lymphocytes correlates with elevated expression of MHC antigens
      as well as co-stimulatory molecules. The aim of this work was to evaluate the
      functional role of the individual CD28 ligands in the induction of primary
      humoral and cellular responses, and to characterize the nature of the immune
      response induced in the presence of selected co-stimulatory molecules. Our data
      show that the primary response is strictly B7 dependent, and that B7-1 and B7-2
      mediate overlapping co-stimulatory functions, as either molecule alone is
      sufficient to initiate an immune reaction. Inhibition of B7-1 and B7-2, however,
      does not lead to tolerance as predicted by the two-signal hypothesis. Rather,
      recognition of antigen in the absence of B7 appears as a null event, since
      subsequent immunogenic stimulation results in a primary response. Blockade of B7
      2 co-stimulatory molecules significantly inhibits antigen-specific IgG1 but not
      IgG2a production, suggesting that B7-2 may direct the development of Th2 cells.
      These data emphasize the critical role of the CD28/B7 pathway in the induction of
      the immune response by DC, which appear to be the initiating antigen-presenting
      cells in situ.

PMID- 9576618
TI  - TCR-MHC class II interaction is required for peripheral expansion of CD4 cells in
      a T cell-deficient host.
AB  - It is well established that T cell-deficient nude and SCID mice can be
      reconstituted by i.v. injection of small numbers of purified peripheral CD4+ T
      cells; however, the requirements for expansion of the transferred T cells in such
      systems are not clear. We show here that blood and lymphoid organs of MHC class
      II-deficient mice (which selectively lack mature CD4+ T cells) cannot be
      reconstituted by transfer of purified splenic CD4+ T cells, whereas TCRalpha
      deficient mice (which lack both CD4+ and CD8+ mature T cells) are readily
      reconstituted. The failure of CD4+ T cell reconstitution in MHC class II
      deficient mice was not due to the presence of CD8+ T cells, since similar results
      were obtained in TCRalpha-MHC class II double-deficient mice. Consistent with
      most previous studies CD4+ T cells in reconstituted TCRalpha-deficient mice had a
      diverse TCR Vbeta repertoire and were predominantly of an activated/memory
      (CD44high) phenotype. Collectively our data demonstrate that the expansion of
      peripheral CD4+ T cells in a T cell-deficient host is dependent upon interactions
      of the TCR with MHC class II.

PMID- 9576619
TI  - CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of
      down-modulating cytotoxic activity.
AB  - Major expansions of CD8hi+CD57+ T lymphocytes frequently occur during human
      immunodeficiency virus (HIV) infection and after transplantation. To investigate
      mechanisms of such cell expansion, we compared the activation and functional
      status of CD8hi+CD57+ and CD57-peripheral blood lymphocytes (PBL) from normal,
      bone marrow transplantation (BMT) and HIV+ donors. The CD8hi+CD57+ PBL from BMT
      and HIV+ donors preferentially displayed CD38 and HLA-DR activation markers
      without correlation between CD8hi+CD57+ percentages and HIV load, the CD45RA+
      isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion,
      CD11b and CD11c in BMT and HIV+ donors but decreased expression of CD62-L, VLA-2
      and VLA-6. The CD8hi+CD57+ cells were positive for perforin and granzyme B and
      spontaneously mediated cytolytic activity in a CD3-redirected assay. In contrast
      the inhibitor of cytolytic functions (ICF) produced by CD8hi+CD57+ cells down
      modulated the CD3-redirected cytolytic activity but only at low levels of CD3
      cross-linking. While CD3-triggering induced a low, if any, short-term
      proliferation of CD8+CD57+ cells, this subset could be amplified after long-term
      stimulation either with mitogens or with HIV antigens, thereby enriched in HIV
      specific T cells producing tumor necrosis factor-alpha. Altogether these data
      suggest that CD8hi+CD57+ cells represent a terminal differentiation state of
      activated effector cytotoxic T lymphocytes which are enriched in antigen-specific
      T cells and down-modulate their own cytolytic potential, thus participating in a
      negative control of effector cell functions during persistent viral infections or
      transplantations.

PMID- 9576620
TI  - Ig heavy chain class switching in Rag-deficient mice.
AB  - To investigate potential roles of the RAG-1 and RAG-2 gene products in Ig heavy
      chain class recombination (CSR), we have generated RAG-1(-/-) and RAG-2(-/-) mice
      which contain both a rearranged Ig HC V(D)J gene (referred to as B1-8) inserted
      into the endogenous Ig heavy chain (HC) locus in place of the JH segments, and a
      rearranged lambda1 light chain (LC) transgene (which are referred to as RAG-1(-/
      )B1-8lambda and RAG-2(-/-)B1-8lambda mice respectively). The B1-8 HC gene and
      lambda LC genes encode proteins that associate to form a complete Ig molecule,
      the expression of which leads to substantial reconstitution of the peripheral B
      cell compartments of RAG-1(-/-)B1-8lambda and RAG-2(-/-)B1-8lambda mice. Both RAG
      1(-/-)B1-8lambda and RAG-2(-/-)B1-8lambda mice have relatively normal levels of
      the various IgG isotypes, but greatly reduced levels of serum IgM and IgA
      compared to normal littermates. Furthermore, RAG-1(-/-)B1-8lambda and RAG-2(-/
      )B1-8lambda B cells activated in vitro with lipopolysaccharide (LPS) or LPS plus
      IL-4 responded similarly to control B cells with respect to surface expression
      and secretion of IgG3, IgG1, IgG2b, IgG2a and IgE, but again were deficient in
      the secretion of IgM. Together, these findings indicate that neither RAG-1 nor
      RAG-2 expression is required for efficient class switching to most HC isotypes in
      B cells.

PMID- 9576621
TI  - Genetic influence on disease course and cytokine response in relapsing
      experimental allergic encephalomyelitis.
AB  - A protracted and relapsing form of experimental allergic encephalomyelitis (EAE)
      develops in the DA rat after immunization with rat spinal cord homogenate (SCH)
      emulsified in incomplete Freund's adjuvant (IFA). The genetic influence on this
      model has been analyzed by immunizing MHC congenic strains on both LEW and DA
      genetic backgrounds, and recombinant inbred strains between DA and E3 rats. An in
      situ hybridization assay was used to examine the expression of mRNA for IFN
      gamma, IL-4, IL-10 and transforming growth factor (TGF)-beta both in sections of
      spinal cords and the antigen-induced expression for these cytokines by
      splenocytes after in vitro stimulation with encephalitogenic MBP peptides. The
      susceptibility of relapsing EAE after immunization with SCH in IFA in the DA
      strain, but not the E3 strain, was correlated with a lack of expression for TGF
      beta in the spinal cord. The recombinant inbred DXEB rats developed a severe EAE
      while surprisingly no signs of disease were observed in the DXEA strain, which
      shares the MHC region with the DXEB strain, after immunization with the MBP 63-87
      peptide. Resistance to relapsing EAE in the DXEA strain correlated with increased
      non-MHC controlled expression for TGF-beta and lack of IFN-gamma in the spinal
      cord. The same pattern of cytokine expression was seen in splenocytes after
      stimulation in vitro with the MBP 63-87 peptide. A spreading of the immune
      response to the MBP 87-110 peptide was seen. Non-MHC genes controlled the quality
      of this response: splenocytes from MBP 63-87 immunized DXEB rats responded in
      vitro towards the MBP 87-110 peptide by expressing mRNA for IFN-gamma, IL-10 and
      IL-4, whereas in the DXEA strain the corresponding response involved IL-4 and TGF
      beta. Taken together these data show that non-MHC controlled expression of mRNA
      for TGF-beta is associated with resistance to EAE.

PMID- 9576622
TI  - Effect of amino acid substitutions in the heavy chain CDR3 of an autoantibody on
      its reactivity.
AB  - In this study, we applied site-directed mutagenesis to the Fab fragment of a
      mouse IgM (IE12) that was previously shown to inhibit the binding of IgG to
      autoantigens by interacting with their variable regions. Its native structure was
      very similar to that of a polyreactive natural IgM (ppc15-30). Indeed, they both
      use the same light chain and the same VH, D and JH segments. However, the N
      regions differ and the D is translated in two different reading frames, giving
      different amino acid compositions of the heavy chain CDR3 (HCDR3). Site-directed
      mutagenesis modified the HCDR3 of IE12 compared to that of the natural antibody
      and the resulting effects on its reactivity were analyzed. Because the HCDR3 of
      IE12 is very rich in aliphatic residues, which are hydrophobic, we replaced them
      with the more hydrophilic residues of the HCDR3 of the polyreactive IgM. In
      addition, we evaluated the impact of the proline residues in the HCDR3 of IE12 on
      its activity, because they are known to restrict backbone flexibility. We found
      that a more hydrophilic HCDR3 conferred to the IE12 Fab a polyreactive profile.
      Prolines seem to play an important role in this context, because when they were
      replaced by glycines, the resulting Fab fragments were highly polyreactive. Our
      results suggest that, for polyreactivity, hydrophilicity and a certain plasticity
      of the HCDR3 seem to be necessary. Greater flexibility of the CDR, particularly
      the HCDR3, might be an important characteristic for polyreactive antibodies.

PMID- 9576623
TI  - In vivo stimulation of polymeric Ig receptor transcytosis by circulating
      polymeric IgA in rat liver.
AB  - Binding of human polymeric IgA ligand to its epithelial cell polymeric Ig
      receptor, pIgR, has been shown to stimulate pIgR apical transcytosis in an in
      vitro system, based on polarized confluent MDCK cells expressing rabbit pIgR. The
      present study aimed at testing whether such a stimulation also occurs in vivo.
      Transcytosis of pIgR was monitored by rat liver output of total secretory
      component (SC) into bile, measured by radial immunodiffusion as the sum of free
      SC and pIgA-bound SC. Whereas in the perfused rat liver system addition of pIgA
      to the perfusate showed no effect, i.v. injection of human and rat pIgA, but not
      of monomeric IgA nor PBS, in living rats significantly increased total bile SC
      output for more than 1 h. Furthermore, depletion of the normal pIgA level
      circulating in the liver before injecting more pIgA was not required to show the
      stimulation. Our data thus strongly suggest that stimulation of liver pIgR
      transcytosis by pIgA ligand binding is physiologically relevant, helping to
      quickly adjust pIgA transport into bile to increase circulating pIgA levels,
      without need for increased SC/pIgR synthesis.

PMID- 9576624
TI  - B lymphocytes secreting IgG linked to latent transforming growth factor-beta
      prevent primary cytolytic T lymphocyte responses.
AB  - B lymphocytes secreting IgG linked to latent transforming growth factor (TGF)
      beta (IgG-TGF-beta) prevent cytolytic T lymphocyte (CTL) responses to unrelated
      antigens in mixed lymphocyte cultures (MLC) so long as resting resident
      macrophages and functional Fc receptors are present. This was shown using IgG
      secreting plaque-forming cells (PFC) to sheep erythrocytes (SRBC) obtained from
      popliteal lymph nodes of mice injected repeatedly in foot pads with SRBC.
      Remarkably, as few as approximately 300 PFC prevented CTL responses of 5 x 10(5)
      normal syngeneic spleen cells in MLC. Supranatants of short-term cultures of PFC
      also prevented CTL responses, and suppression was prevented by eliminating or
      dissociating IgG and TGF-beta present in supranatants or by antibody against
      active TGF-beta. Furthermore, the latency-associated peptide of latent TGF-beta
      was detected in approximately 10% of foci of IgG captured from single PFC,
      indicating that at least some B lymphocytes secrete IgG-TGF-beta as a complex.
      Resting resident macrophages (which do not produce latent TGF-beta) and
      functional Fc receptors were required for suppression, consistent with idea that
      IgG-TGF-beta is taken up through Fc receptors for IgG and that active TGF-beta,
      cleaved from latent TGF-beta of the complex, is delivered directly to potentially
      responding CTL. If CTL responses in man are similarly regulated by B lymphocytes,
      then an ongoing B cell response in patients with chronic viral infections or
      bearing immunogenic cancers may prevent effective therapeutic vaccination.

PMID- 9576625
TI  - T cell unresponsiveness in vitro can be due to activation in vivo.
AB  - During investigations into the behaviour and fate of ovalbumin (OVA)-specific
      CD8+ T cells in a TCR transgenic system, cytotoxic T lymphocyte (CTL) activity
      (as measured by classical in vitro stimulation followed by 51Cr-release assay)
      was found to be reduced after OVA peptide administration. This paradoxically
      occurred even during the peak of activation and expansion of these T cells. The
      reduced responsiveness occurred for both classical CTL assays and in vitro
      proliferation assays, and would apparently be consistent with induction of
      anergic or suppressor T cells. Instead, we provide evidence that in vivo peptide
      treatment generated activated killers which consequently killed the stimulator
      cells during in vitro culture, thus resulting in the unresponsive phenotype. In
      co-culture experiments, the proliferation and classical CTL activity were
      severely reduced when naive OVA-specific CD8+ T cells (OT-I) cells were co
      cultured with cells from OVA peptide-treated mice. Moreover, cells obtained after
      peptide injection did not require in vitro stimulation to be able to kill target
      cells. Therefore, activation of killers in vivo should be considered as one
      pathway whereby unresponsiveness is found in assays requiring in vitro
      stimulation.

PMID- 9576626
TI  - The Eph family receptors and ligands.
AB  - The Eph family is the largest of all known tyrosine kinase receptor-ligand
      systems. They are expressed in distinct, but overlapping, spatial and temporal
      patterns during embryonic development and postnatal life, and function in a
      variety of morphogenic events. The best known function is their role in the
      guidance of migration of axons and cells in the nervous system through repulsive
      interactions. They may also play a role in angiogenesis, tissue patterning, and
      tumor formation.

PMID- 9576627
TI  - Calcium-dependent desensitizing function of the postsynaptic neuronal-type
      nicotinic acetylcholine receptors at the neuromuscular junction.
AB  - Several subunits that commonly have been regarded as neuronal-type nicotinic
      acetylcholine receptor (nAChR) subtypes, have been found in the postjunctional
      endplate membrane of adult skeletal muscle fibres. The postsynaptic function of
      these neuronal-type nAChR subtypes at the neuromuscular junction has been
      investigated by using aequorin luminescence and fluorescence confocal imaging. A
      biphasic elevation of intracellular Ca2+ is elicited by prolonged nicotinic
      action at the mouse muscle endplates. The fast and slow Ca2+ components are
      operated by a postsynaptic muscle- and colocalized neuronal-type nAChR,
      respectively. Neuromuscular functions may be regulated by a dual nAChR system to
      maintain the normal postsynaptic excitability. Certain neuronal-type nAChR may be
      endowed with the same functional role in the central nervous system also.

PMID- 9576628
TI  - Presynaptic facilitation of synaptic transmission in the hippocampus.
AB  - Biochemical and genetic characterization of proteins in presynaptic axon
      terminals have led to models of the biochemical pathways underlying synaptic
      vesicle docking, activation, and fusion. Several studies have attempted recently
      to assign a precise physiological role to these proteins. This review deals with
      some of these studies, concentrating on those performed with hippocampal
      synapses. It is shown that changes in the state of these presynaptic proteins,
      together with modifications in Ca2+ dynamics in axon terminals, functionally
      determine the level of basal synaptic transmission, and underlie
      pharmacologically induced and activity-dependent facilitation of transmitter
      release in the central nervous system.

PMID- 9576629
TI  - Apoptosis, cancer and cancer therapy.
AB  - Apoptosis is a specific process that leads to programmed cell death through the
      activation of an evolutionary conserved intracellular pathway leading to
      pathognomic cellular changes distinct from cellular necrosis. Apoptosis is
      essential in the homeostasis of normal tissues of the body, especially those of
      the gastrointestinal tract, immune system and skin. There is increasing evidence
      that the processes of neoplastic transformation, progression and metastasis
      involve alterations in the normal apoptotic pathways. Furthermore, the majority
      of chemotherapeutic agents as well as radiation utilize the apoptotic pathway to
      induce cancer cell death. Resistance to standard chemotherapies also seems to be
      determined by alterations in the apoptotic pathways of cancer cells. Therefore,
      understanding the signals of apoptosis and the mechanism of apoptosis may allow
      the development of better chemo- or radiotherapeutic regimens for the treatment
      of cancer. Finally, components of the apoptotic pathway may represent potential
      therapeutic targets using gene therapy techniques.

PMID- 9576630
TI  - Molecular advances in the etiology and treatment of colorectal cancer.
AB  - The diagnosis and treatment of colorectal cancer remains a formidable health care
      problem. Colorectal cancer is the second most frequently diagnosed cancer in both
      men and women in Western countries and accounts for over 55,000 deaths annually
      in the United States alone. Cancer of the colon and rectum is eminently curable
      by surgical resection if identified early; however, despite our best efforts,
      patient survival from this disease has changed little over the past 50 years.
      With the advent of molecular and genetic techniques, a number of novel
      discoveries have been made in the last decade which have greatly expanded our
      understanding of the etiology and cellular mechanisms contributing to the
      development and subsequent progression of colorectal cancer. This review
      summarizes the recent molecular advances in the understanding of both familial
      (HNPCC and FAP) and sporadic colorectal cancers. The numerous scientific advances
      described in this review offer the promise of the development of novel
      chemotherapeutic agents, more accurate prognostic indicators and better screening
      techniques.

PMID- 9576631
TI  - Advances in the early detection, diagnosis, and staging of pancreatic cancer.
AB  - Pancreatic cancer is an aggressive disease with a dismal prognosis. It has long
      been regarded as one of the most difficult cancers to accurately diagnose and
      stage preoperatively. The purpose of this review is to provide an update of the
      state-of-the-art for early detection, diagnosis, and staging of pancreatic
      cancer. These methods include spiral CT scans, magnetic resonance imaging,
      positron emission tomography (PET) imaging, laparoscopy, endoscopic ultrasound,
      CA 19-9 serology, fine needle aspiration cytology, ERCP brush cytology, and
      screening for p53 and ras oncogenes. These advanced techniques should help us to
      detect pancreatic cancers in high-risk populations at a curative stage and to
      decrease pancreaticoduodenectomies for benign disease which could otherwise be
      treated with less morbid procedures. In addition, these tests will help reliably
      diagnose pancreatic cancer preoperatively.

PMID- 9576632
TI  - Principles of chronic venous access: recommendations based on the Roswell Park
      experience.
AB  - At Roswell Park Cancer Institute, we have seen a dramatic increase in the need
      for long-term venous access. Chronic venous catheters are an indispensible part
      of the treatment provided to oncology patients. Cancer patients are often at
      higher risk for complications secondary to their underlying disease and
      treatments. These risks may be minimized by paying close attention to several
      important aspects of central line placement. These include matching individual
      patient needs with the access device most suited to those needs, a thorough
      preoperative assessment, and the safest and most appropriate operative approach
      for placement. Likewise, the prompt recognition and treatment of complications
      when they do occur is crucial to the care of these patients. In order to optimize
      the care of patients with long-term venous access devices, we have reviewed our
      experience of over 700 vascular access consultations and offer the following
      recommendations.

PMID- 9576633
TI  - Cellular effects of hypercholesterolemia in modulation of cancer growth and
      metastasis: a review of the evidence.
AB  - Hypercholesterolemia and increased cancer risk have been associated, particularly
      with the high fat diets characteristic of Western societies. We were interested
      in the possible association between preexisting hypercholesterolemia and the
      rapidity and extent of tumor metastases in these patients. To date there has been
      only a few studies that have suggested and explored this determinant of cancer
      metastases although it may play a role in a subset of patients who develop
      cancers. This article will review the literature on the effects of LDL
      cholesterol on cell proliferation and differentiation and speculate on mechanisms
      of involvement of a hypercholesterolemic milieu on cancer progression and
      enhancement of metastatic potential.

PMID- 9576634
TI  - CD4 and CD8 lymphocyte subsets in cerebrospinal fluid and peripheral blood from
      patients with multiple sclerosis, meningitis and normal controls.
AB  - OBJECTIVES: To study the distribution of CD4+ and CD8+ T-cell subsets in
      cerebrospinal fluid (CSF) and peripheral blood from patients with multiple
      sclerosis (MS), meningitis, other neurological diseases and healthy controls.
      MATERIAL AND METHODS: The expression of markers for naive and memory cells
      (CD45RA+ and CD45R0+), and helper/inducer cells (CD29+) on CD4+ cells as well as
      CD45R0+ and killer/effector (S6F1+) on CD8+ cells was investigated in
      cerebrospinal fluid (CSF) and peripheral blood from patients with multiple
      sclerosis (n=28), meningitis (n=13), other neurological diseases (n=16), and
      healthy controls (n=16) by 2-color flow cytometry. RESULTS: The majority of T
      cells in the CSF of the 4 groups exhibited the phenotype of memory cells
      (CD45R0+) on both CD4+ and CD8+ cells. The proportion of helper/inducer
      (CD29+CD4+ in CD4+) cells was also larger in the CSF compared to peripheral blood
      in the 3 patient groups and controls investigated. In contrast, CD8+ cells with
      killer/effector (S6F1+) phenotype were fewer in CSF compared to peripheral blood
      in all 4 groups. There were no significant differences between patients and
      controls regarding the distribution of these activation markers in the CSF or
      peripheral blood. CONCLUSION: Our observations support the notion that activated
      T cells of both CD4+ and CD8+ phenotype selectively pass the blood-brain barrier
      under both pathological and normal conditions.

PMID- 9576635
TI  - Increased expression of adhesion molecule CD18 (LFA-1beta) on the leukocytes of
      peripheral blood in patients with acute ischemic stroke.
AB  - OBJECTIVES: The aim of this study was to investigate whether adhesion molecules
      play a role in acute ischemic stroke. MATERIAL AND METHODS: Using
      immunofluorescence phenotyping and flow cytometry, the expression of leukocyte
      adhesion molecules CD54, CD11a, CD11b and CD18 in peripheral blood were measured
      within 12 h after onset of ischemia in 20 patients with stroke. Follow-up
      measurements were performed at 7 and 30 days after ictus. RESULTS: CD18
      immunofluorescence was significantly increased on the leukocytes within 12 h
      after onset in patients with stroke compared with the age-matched control group
      (20 patients with other neurological diseases). Follow-up measurement of CD18
      revealed normal results as found in the control group. CONCLUSION: Our data
      support the idea that adhesion molecules are involved in tissue injury in
      ischemic stroke.

PMID- 9576636
TI  - The anterior inferior cerebellar artery infarcts: a clinical-magnetic resonance
      imaging study.
AB  - Acute infarcts of the anterior inferior cerebellar artery (AICA) are unusual. We
      report 15 cases of AICA infarcts and their correlation with the topography of the
      lesion by brain MRI. During 2 years we prospectively identified 7 cases of AICA
      infarcts among 770 acute strokes (0.9% of the acute strokes seen in our
      department). We studied these cases and also another 8 that we found
      retrospectively. Most patients (8/15) had a unilateral affectation of both middle
      cerebellar peduncle (MCP) and inferior lateral pontine area (ILP), in these cases
      the main symptoms were vertigo, ataxia, peripheral facial palsy and hypoacusia.
      Two other patients had isolated MCP infarcts and were characterized by peripheral
      vertigo and ataxia, without hypoacusia or facial palsy. Another 2 patients had
      isolated ILP territory infarct characterized by vertigo, left peripheral facial
      palsy without hypoacusia and mild or no ataxia. One patient had a Gasperini
      syndrome. Finally 3 patients had bilateral AICA infarcts due to basilar
      thrombosis. The etiology was atherosclerosis in 9 patients, lacunar due to
      hypertension in 1, cardiac embolism in 1, migraine in 1 and unknown in 3. Among
      the 15 patients only 2 died, both with AICA plus infarcts. In the remaining
      patients a follow-up during a mean of 31 months (3 months to 12 years) showed no
      recurrences.

PMID- 9576637
TI  - Dye dilution and oximetry for detection of patent foramen ovale.
AB  - OBJECTIVES: Patent foramen ovale (PFO) is a risk factor for stroke of
      undetermined (cryptogenic) origin. Low cost and non-invasive bedside tests for
      detection of PFO are needed as alternatives to contrast transesophageal
      echocardiography. We investigated whether dye dilution curves and oximeter
      recordings are useful for detecting PFO and what is the prevalence of PFO in
      patients with cryptogenic stroke determined with these bedside methods. We also
      studied whether stroke risk factors, number of brain lesions, and stroke
      recurrence rates were different in patients with an unexplained stroke with and
      without PFO. MATERIAL AND METHODS: Dye dilution curves and oximeter recordings
      with non-invasive earpiece apparatus were obtained in 59 patients aged under 50
      years who had had a cryptogenic brain infarction. The number of ischemic lesions
      in the brain was counted by MRI. RESULTS: PFO was found in 24 (41%) of 59
      patients. There was a 100% concordance in results obtained by dye dilution and by
      oximetry. Risk factors for stroke were similar in subjects with PFO and those
      without PFO. No significant association was found between PFO and Valsalva-like
      activity at stroke onset. Those with PFO did not have more ischemic lesions
      detected by MRI nor did they have more recurrent ischemic episodes. CONCLUSION:
      Dye dilution and oximetry are cheap and useful methods for detection of PFO and
      could be used for screening of the risk of paradoxical embolism. Because these 2
      methods were not compared with the golden standard, transesophageal
      echocardiography, the specificity and sensitivity of the tests remain unsettled.

PMID- 9576638
TI  - Kanji-predominant alexia in advanced Alzheimer's disease.
AB  - OBJECTIVES: Oral reading is preserved until the late stage of Alzheimer's disease
      (AD). However, it is unknown whether reading of kanji and kana is differentially
      impaired in Japanese AD patients. The purpose of this study was to examine alexic
      pattern in AD as related to two script systems. MATERIAL AND METHODS: In 18
      severe AD patients, reading performance was compared among kana characters,
      monographic kanji words, and kana-transcribed words. Auditory comprehension was
      also examined. RESULTS: With increased severity of dementia, kanji reading was
      clearly more impaired than kana reading, which was relatively unaffected. Graphic
      complexity and frequency of the kanji influenced the performance variously among
      the patients. Dissociation between kanji reading and comprehension was also
      noted. CONCLUSION: As a result of multiple cognitive deficits, kanji reading is
      more impaired than kana reading in AD, but the difference is apparent only in the
      very late stage. Our findings suggest that kanji can be read correctly without
      meaning.

PMID- 9576639
TI  - Dose-dependent CSF acetylcholinesterase inhibition by SDZ ENA 713 in Alzheimer's
      disease.
AB  - INTRODUCTION: This study evaluates the activity of SDZ ENA 713, a centrally
      selective acetylcholinesterase (AChE) inhibitor, in the cerebral spinal fluid
      (CSF) of patients with Alzheimer's disease (AD), and its relationship to central
      and peripheral pharmacokinetic parameters. METHODS: Eighteen AD patients were
      enrolled in this open-label, multiple-dose study. Patients were titrated in 1 mg
      bid/week increments to target doses of 1, 2, 3, 4, 5, or 6 mg bid SDZ ENA 713.
      After patients had been maintained at their target dose for at least 3 days,
      continuous CSF samples were obtained via a lumbar catheter for 12.5 h, beginning
      0.5 h prior to the final dose of SDZ ENA 713. RESULTS: Dose-dependent inhibition
      of CSF AChE was significantly correlated (P < 0.05) with plasma drug and
      metabolite concentrations. The 6 mg bid treatment group showed a maximum mean
      inhibition of 62% at 5.6 h post-dose. CONCLUSION: Rapid, sustained, dose
      dependent inhibition of CSF AChE suggests that SDZ ENA 713 has therapeutic
      potential in AD patients.

PMID- 9576640
TI  - Subclinical cerebral lesion accumulation on serial magnetic resonance imaging
      (MRI) in patients with hypertension: risk factors.
AB  - OBJECTIVES: We investigated the occurrence in hypertensive patients of new
      subclinical changes in the brain by serial magnetic resonance imaging (MRI).
      METHODS: MRI was performed serially in 98 hypertensive subjects without
      neurologic deficits at least once a year for 3 years. All received
      antihypertensive medicines Blood pressure, serum lipids, diabetes mellitus, body
      mass index (BMI), and other clinical factors were correlated with results.
      RESULTS: Seventy-nine patients had unchanged MRI findings, while 19 developed new
      lesions (silent lacunar infarct and etat crible in 3, silent lacunar infarct in
      9, and etat crible in 7). Follow-up systolic blood pressures were significantly
      higher than individual baselines in the unchanged group, while the follow-up
      diastolic blood pressures in the new lesion group were significantly lower than
      in the unchanged group. BMI was significantly lower in the new lesion group.
      Follow-up HbA1c levels in both groups were significantly higher than at baseline.
      Diabetes mellitus was significantly more frequent in the new lesion group than in
      the unchanged group. No significant differences were apparent in serum lipids
      level, prescribed antihypertensive medications, and other potential risk factors.
      CONCLUSIONS: New subclinical MRI changes in hypertensive subjects occurred
      relatively frequently (19 of 98 subjects, or 19.4%). An excessive fall in
      diastolic blood pressure, diabetes mellitus, and low BMI emerged as candidate
      risk factors for these changes.

PMID- 9576641
TI  - Clinical presentation and therapeutic outcome in 26 patients with primary CNS
      lymphoma.
AB  - This retrospective study analyzes clinical features and therapeutic outcome in 26
      immunocompetent patients with primary central nervous system lymphoma (PCNSL).
      Most patients presented with personality changes. PCNSL lesions were mainly iso-
      or hyperdense, enhancing lesions on CT scan, hypointensive on T1-, and
      hyperintensive on T2-weighted MRI. Multiple lesions were found in about 60% of
      patients. Nine of 11 patients receiving radiotherapy alone showed complete
      remission (CR). Median survival time after diagnosis (MST) was 13 months. Seven
      patients received intravenous and intrathecal methotrexate, radiotherapy, and
      postirradiation intravenous cytarabine. Six of these patients had CR and 5
      patients are alive in CR after a median follow-up of 12 months. Five patients
      received various other radiochemotherapy regimens (MST 6 months), and 3 patients
      died before receiving any radio- or chemotherapy. Our preliminary treatment
      results show a tendency to improved survival with radiochemotherapy. This is
      consistent with pertinent data from the literature which favors radiochemotherapy
      for patients with PCNSL.

PMID- 9576642
TI  - Recognition of neurologic diseases in geriatric inpatients.
AB  - OBJECTIVES: To determine the prevalence of neurologic disease and the diagnostic
      impact of neurologic consultation on a geriatric inpatient unit. MATERIAL AND
      METHODS: Consecutively admitted patients were prospectively assessed by a
      neurologist and by medical house staff on a geriatrics unit over a 4-month
      period. Neurologic diagnoses were compared. RESULTS: Fifty-eight men, aged 76.4+/
      8.7 years old (mean+/-SD), had 1.4+/-1.1 new or revised neurologic diagnoses made
      by the neurologist. The prevalence of neurologic disorder was: gait or balance
      disorder (90%); cognitive disorders (71%); neuromuscular disorder (59%);
      cerebrovascular disorder (38%); and extrapyramidal disorders (22%). New diagnoses
      were made by the neurologist among the cognitive (40%), neuromuscular (36%) and
      cerebrovascular disorders (19%). CONCLUSIONS: Neurologic disease is highly
      prevalent in geriatric inpatients. A neurologist's assessment resulted in altered
      diagnoses suggesting that neurologists should play a role in geriatric assessment
      and in education of health professionals caring for the elderly.

PMID- 9576643
TI  - The effect of human leukocyte antigen disparity on cyclosporine neurotoxicity
      after allogeneic bone marrow transplantation.
AB  - PURPOSE: We examined the relationship between human leukocyte antigen (HLA)
      matching and the development of cyclosporine (CyA) neurotoxicity in patients
      undergoing allogeneic bone marrow transplantation, and determined the frequency
      and imaging characteristics of CyA neurotoxicity in these patients. METHODS:
      Records of 87 patients who underwent allogeneic bone marrow transplantation were
      reviewed. Eight patients who presented with visual disturbance and/or seizures
      and had MR imaging within 24 hours were identified. Transplant donor relatedness
      was examined, and patients' imaging studies were reviewed. Clinical parameters,
      including blood pressure, CyA, creatinine, and magnesium levels, and the presence
      of graft-versus-host disease were reviewed. RESULTS: CyA neurotoxicity was seen
      more frequently in HLA-mismatched and unrelated donor transplants. The frequency
      of CyA neurotoxicity was 4% for patients with a 5/6 or 6/6 HLA match, 13% for
      matched unrelated donor transplants, and 50% for haplotypic 3/6 or 4/6
      transplants. Patients with matched unrelated donor transplants and haplotypic
      transplants presented earlier in the posttransplant time course and had decreased
      survival time relative to patients with HLA-matched transplants. Imaging
      abnormalities most commonly affected the occipital lobes and the posterior
      cerebral hemispheres; both cortical and white matter involvement was identifiable
      as T1 hypointense and T2 hyperintense signal with associated gyral swelling and
      sulcal effacement on the initial MR studies. Hypodensity in the affected areas
      was noted on CT scans. Contrast enhancement was seen in HLA-mismatched and
      unrelated transplants only. Follow-up imaging showed interval decreases in
      subcortical edema; however, residual signal abnormality, primarily affecting the
      cortex, was present in all cases and seen best on proton density-weighted MR
      images. CONCLUSION: The frequency of severe CyA neurotoxicity increases with
      increasing HLA disparity, suggesting that immune factors may play a role. CyA
      neurotoxicity appears to represent a spectrum of disease processes. Disruption of
      the blood-brain barrier as well as hypoxic or vasculitic cortical injury
      resulting in MR-detectable cortical signal abnormalities may occur in severe
      cases.

PMID- 9576644
TI  - Antiphospholipid antibodies: findings at arteriography.
AB  - PURPOSE: The purpose of this study was to determine the frequency and types of
      abnormalities at arteriography in patients with antiphospholipid antibodies (APA)
      and ischemic cerebrovascular events. METHODS: Twenty-three patients with APA and
      ischemic cerebrovascular events who underwent arteriography were identified.
      Patients over the age of 65 years were excluded. No patients met diagnostic
      criteria for systemic lupus erythematosus. All angiograms were reviewed by two
      neuroradiologists. RESULTS: Seventeen patients (74%) between the ages of 28 and
      64 years (average age, 40 years) had abnormal angiograms. Sixteen patients had
      arterial abnormalities and one had dural sinus thrombosis. Ten had solely
      intracranial abnormalities (nine arterial and one venous), six had solely
      extracranial arterial abnormalities, and one had both intracranial and
      extracranial arterial abnormalities. Intracranial arterial abnormalities included
      stem or branch occlusions of the cerebral or basilar arteries, which were
      generally solitary (six patients), and findings suggestive of vasculitis (four
      patients). Four patients had stenoses of the origins of two or more great
      vessels. Two patients had extracranial internal carotid artery stenoses or
      occlusions that were not typical of atheromatous disease, considered to be
      embolic in one patient. In another patient, a stenosis of the origin of the
      internal carotid artery was present that appeared typical of atheromatous
      disease. Infarctions were seen on CT or MR studies in 13 of 17 patients with
      abnormal angiograms. CONCLUSION: In our group of patients, typical atheromatous
      lesions at the common carotid artery bifurcation were rare. Some lesions that are
      infrequent in the general stroke population (eg, vasculitis-like findings and
      stenoses at the origin of great vessels) were common. Patients with APA and
      cerebrovascular events appear to differ from the general stroke population with
      regard to types of arterial abnormalities seen at arteriography.

PMID- 9576645
TI  - Tributary venosinus occlusion and septic cavernous sinus thrombosis: CT and MR
      findings.
AB  - PURPOSE: In autopsy reports of patients who died of septic cavernous sinus
      thrombosis, tributary venosinus occlusion has been a common finding related to
      intracranial inflammatory complications. The purpose of this article is to
      illustrate the MR and CT appearance of septic cavernous sinus thrombosis and
      tributary venous occlusion. METHODS: Over a period of 7 years, eight patients
      with septic cavernous sinus thrombosis were examined by contrast-enhanced thin
      section CT. The CT scans of these eight patients and those of 30 healthy control
      subjects were assessed independently and subjectively by two blinded readers to
      ascertain the presence, size, and density of areas of nonopacification within the
      cavernous sinus and the presence of filling defects and dilation of tributary
      veins and venous sinuses. In six subjects, MR images supplemented by a contrast
      enhanced spoiled gradient-recalled acquisition in the steady state (SPGR)
      sequence were assessed with respect to the presence of filling defects,
      expansion, and signal abnormalities within the cavernous sinus and tributary
      veins and sinuses. The MR and CT findings were compared. RESULTS: The CT studies
      of the eight patients were consistently differentiated from those of the control
      subjects by the two readers. Contrast-enhanced CT findings in patients included
      areas of nonopacification that were present within the cavernous sinus
      bilaterally in six cases and unilaterally in two. The size of the filling defects
      exceeded 7 mm in 76% of thrombosed cavernous sinuses compared with 9% of control
      subjects. The mean density of filling defects in patients differed significantly
      from those in control subjects. Comparison of the MR and CT findings in six cases
      showed the contrast-enhanced SPGR sequence to be equivalent to CT with respect to
      delineation of filling defects. CONCLUSION: Contrast-enhanced high-resolution CT
      findings indicate that venosinus thrombosis associated with septic cavernous
      sinus thrombosis is not restricted to the superior ophthalmic vein and is more
      common than previously assumed. A contrast-enhanced SPGR MR sequence may be used
      as a reliable alternative to establish the diagnosis of cavernous sinus and
      tributary venosinus thrombosis.

PMID- 9576646
TI  - Cerebrospinal fluid fistula: detection with MR cisternography.
AB  - PURPOSE: Our goal was to assess the role of MR cisternography in the examination
      of patients with suspected CSF rhinorrhea. METHODS: MR cisternography was
      performed as a heavily T2-weighted fast spin-echo study with fat suppression and
      video reversal of the images in 37 patients over a 3-year interval. Twenty-four
      of the patients subsequently had exploratory surgery for fistula. Statistical
      analysis of the surgical results was compared with the findings at MR
      cisternography. RESULTS: MR cisternography showed significant correlation with
      surgical findings, with sensitivity, specificity, and accuracy of 0.87, 0.57, and
      0.78, respectively. CONCLUSION: MR cisternography proved to be an accurate
      diagnostic imaging technique in the evaluation of suspected CSF rhinorrhea.

PMID- 9576647
TI  - Evaluation of high-resolution CT and MR cisternography in the diagnosis of
      cerebrospinal fluid fistula.
AB  - PURPOSE: We undertook this study to determine the accuracy of MR cisternography
      and plain high-resolution CT as a noninvasive alternative to CT cisternography in
      the diagnosis of CSF fistula in patients with clinically suspected CSF
      rhinorrhea. METHODS: Forty-five consecutive patients with clinically suspected
      CSF rhinorrhea were examined prospectively for CSF fistula with MR cisternography
      and plain high-resolution CT. Twenty-one patients also underwent CT
      cisternography. The MR imaging technique included 3-mm thin-section T1-weighted
      coronal sequences and fast spin-echo T2-weighted coronal, axial, and sagittal
      sequences in the supine position. The plain high-resolution CT study included 3
      mm and sometimes 1- to 1.5-mm thin coronal sections in the prone position.
      Similar sequences were used after injecting nonionic contrast material
      intrathecally via lumbar puncture for the CT cisternographic study. The plain
      high-resolution CT and MR cisternographic studies were compared with results of
      CT cisternography; surgical findings were used as the standard of reference.
      RESULTS: Plain high-resolution CT successfully depicted the presence or absence
      of CSF fistula in 42 of 45 patients, whereas MR cisternography was correct in 40
      patients. MR cisternography or plain high-resolution CT correctly showed the
      site(s) of CSF fistula leakage in 36 of the 38 cases proved surgically. The
      combined techniques also correctly indicated the absence of CSF leakage in seven
      cases, six of which were confirmed at CT cisternography. Both MR cisternography
      and high-resolution CT failed to definitively locate the CSF fistula in two
      patients. High-resolution CT was accurate in 93% of patients, whereas MR
      cisternography was accurate in 89% of patients. The combination of high
      resolution CT and MR cisternography was accurate in 96% of patients. CONCLUSION:
      In the presence of clinically diagnosed CSF leakage, the combination of MR
      cisternography and plain high-resolution CT is highly accurate in locating the
      site and extent of CSF fistula and should be considered a viable noninvasive
      alternative to CT cisternography.

PMID- 9576648
TI  - Diagnosis of brain death using two-phase spiral CT.
AB  - PURPOSE: The purpose of this study was to determine the utility of spiral CT in
      the diagnosis of brain death. METHODS: Spiral CT was evaluated prospectively in
      14 brain-dead patients and in 11 healthy subjects. A two-phase protocol was used.
      Twenty seconds after intravenous injection of a nonionic iodinized contrast
      medium, the CT table was drawn through the gantry at a rate of 10 mm/s while
      scanning was in progress. The second scanning phase was started automatically a
      mean of 54 seconds later, using the same parameters. Opacification or absence of
      opacification of carotid, vertebral, and basilar arteries and intracerebral veins
      was ascertained for each image in both phases. The diagnosis of brain death was
      confirmed by elecroencephalography (n = 7), angiography (n = 5), or both (n = 2).
      Statistical analysis with the Fisher exact test enabled us to compare the brain
      dead patients with the healthy control subjects. RESULTS: In brain death, the
      pericallosal and terminal arteries of the cortex did not opacify during the two
      phases of spiral CT, whereas the superficial temporal arteries were always
      visible. The internal cerebral veins, the great cerebral vein, and the straight
      sinus did not opacify, whereas the superior ophthalmic veins were visible on both
      sides 13 times. For each vessel type, specificity was 100% for nonvascular
      opacification criteria on the right and left sides. CONCLUSION: Two-phase spiral
      CT can demonstrate the absence of intracerebral blood flow in brain death.

PMID- 9576649
TI  - Progressive brain failure after diffuse hypoxic ischemic brain injury: a serial
      MR and proton MR spectroscopic study.
AB  - The findings at sequential MR imaging and proton MR spectroscopy of a patient
      with profound hypoxic-ischemic brain injury are reported. The pattern of
      structural and biochemical changes observed closely reflected the known evolution
      of postasphyxic brain degeneration. Particularly noteworthy were the sharp
      decrease of cortical N-acetylaspartate in the acute phase, suggesting the
      severity of the neuronal insult, and the subsequent progressive increase of
      choline, paralleling the delayed degeneration of white matter.

PMID- 9576650
TI  - In vivo three-dimensional MR microscopy of mice with chronic relapsing
      experimental autoimmune encephalomyelitis after treatment with insulin-like
      growth factor-I.
AB  - PURPOSE: The purpose of this study was to determine the ability of three
      dimensional in vivo MR microscopy to depict the treatment effects of insulin-like
      growth factor-I (IGF-I) in SJL mice with chronic relapsing experimental
      autoimmune encephalomyelitis (crEAE). METHODS: The experiments were performed at
      4.7-T on 10 crEAE mice and on one set of control animals. Five crEAE mice were
      treated with IGF-I and five were treated with a placebo. RESULTS: In the crEAE
      mice treated with the placebo, in vivo MR microscopy showed areas of abnormal
      signal throughout the cerebrum, brain stem, and cerebellum. These findings were
      not present in either the IGF-I-treated mice or the normal control animals. The
      diffuse alterations in signal intensity in the placebo-treated crEAE mice were
      not identified on histologic sections of the same areas. CONCLUSION: Differences
      between the IGF-I- and placebo-treated groups may reflect changes in
      stabilization or permeability of cell membranes and/or of the blood-brain
      barrier, although other alternative contrast mechanisms could be playing a role.
      In vivo MR microscopy depicted changes resulting from treatment of crEAE with IGF
      I.

PMID- 9576651
TI  - MR volumetric analysis of the human entorhinal, perirhinal, and temporopolar
      cortices.
AB  - PURPOSE: Our purpose was to investigate the normal volumes of the human
      entorhinal, perirhinal, and temporopolar cortices on MR imaging studies using a
      customized program. METHODS: We designed a protocol in which the volumes of the
      entorhinal, perirhinal, and temporopolar cortices were determined from coronal MR
      images using anatomic landmarks defined on the basis of cytoarchitectonic
      analyses of 49 autopsy cases. MR volumetry of these cortical areas was performed
      in 52 healthy volunteers. RESULTS: The overall mean volumes were 1768 +/- 328
      mm3/1558 +/- 341 mm3 (right/left) for the entorhinal cortex, 2512 +/- 672
      mm3/2572 +/- 666 mm3 for the perirhinal cortex, and 2960 +/- 623 mm3/3091 +/- 636
      mm3 for the temporopolar cortex. The right entorhinal cortex was 12% larger than
      the left. The volume of the temporopolar cortex was reduced bilaterally by 13% in
      the older age group compared with younger subjects, while the volumes of the
      entorhinal and perirhinal cortices were unaffected by age. There were no
      differences between men and women in the volumes of any of the three cortices.
      CONCLUSION: Our method provides a tool by which to measure volumes of the
      entorhinal, perirhinal, and temporopolar cortices on coronal MR images.

PMID- 9576652
TI  - Proton MR spectroscopy in Lesch-Nyhan disease.
AB  - In vivo proton spectra for four patients with Lesch-Nyhan disease and four
      control subjects matched for age and sex were acquired from voxels (1.5 x 1.5 x
      1.5 cm3) placed in the prefrontal cortex and striatum. The patients with Lesch
      Nyhan disease had decreased metabolites, especially N-acetylaspartate and
      glutamate/glutamine, only in the prefrontal cortex as compared with the control
      group. These findings suggest axonal loss in the prefrontal area of this
      population. The cortical glutamate/glutamine peak decrement does not confirm
      cytopathologic studies of Lesch-Nyhan disease and deserves further investigation.

PMID- 9576653
TI  - Patterns of lesion development in multiple sclerosis: longitudinal observations
      with T1-weighted spin-echo and magnetization transfer MR.
AB  - PURPOSE: We evaluated the appearance of enhancing multiple sclerosis (MS) lesions
      on unenhanced T1-weighted MR images and the natural course of enhancing MS
      lesions on serial unenhanced T1-weighted and magnetization transfer (MT) MR
      images. METHODS: One hundred twenty-six enhancing lesions were followed up
      monthly for 6 to 12 months to determine their signal intensity on unenhanced T1
      weighted and MT MR images. At the time of initial enhancement, the size of the
      lesion and the contrast ratio of enhancement were calculated for each enhancing
      lesion. During follow-up, the contrast ratio on the corresponding unenhanced T1
      weighted image was measured, and an MT ratio (MTR) was calculated. RESULTS:
      Twenty-five enhancing lesions (20%) appeared isointense and 101 lesions (80%)
      appeared hypointense relative to normal-appearing white matter on unenhanced T1
      weighted images. During 6 months of follow-up, four MR patterns of active lesions
      were detected: initially isointense lesions remained isointense (15%); initially
      isointense lesions became hypointense (5%, most of which reenhanced); initially
      hypointense lesions became isointense (44%); and initially hypointense lesions
      remained hypointense (36%). MTR was significantly lower for hypointense lesions
      as compared with isointense lesions at the time of initial enhancement. For
      lesions that changed from hypointense to isointense, MTR increased significantly
      during 6 months of follow-up. Multiple regression analysis showed that strongly
      decreased MTR at the time of initial enhancement and enhancement duration of more
      than one scan were predictive of a hypointense appearance on unenhanced T1
      weighted images at 6 months' follow-up. Ring enhancement was found to be the only
      (weak) predictor of persistently hypointense signal intensity. CONCLUSION: Most
      enhancing lesions appear slightly to significantly hypointense on unenhanced T1
      weighted images. Although most hypointensities are reversible, only those lesions
      that fail to recover on unenhanced T1-weighted and MT images may have
      considerable irreversible structural changes.

PMID- 9576654
TI  - Intraobserver and interobserver variability in measuring changes in lesion volume
      on serial brain MR images in multiple sclerosis.
AB  - PURPOSE: We evaluated the intraobserver and interobserver variability in
      measuring long-term changes in the volume of brain lesions on 5- and 3-mm-thick
      MR sections in patients with multiple sclerosis. METHODS: Eighteen 18 patients
      were scanned on two separate occasions with a mean interval of 16.4 months
      between the two examinations. In each session, a scan with 24 contiguous 5-mm
      thick axial sections and another with 40 contiguous 3-mm-thick axial sections was
      acquired consecutively without moving the patient. We assessed MR lesion load by
      using a semiautomated local thresholding technique. RESULTS: Lesion volume was
      significantly higher on images with 3-mm-thick sections than on those with 5-mm
      thick sections both at baseline and at follow up. Significant increases in total
      lesion volume were observed during the follow-up period on images obtained with
      both 5- and 3-mm-thick sections. The intra- and interobserver variability in
      measurements of changes in lesion volume was significantly higher on images with
      5-mm-thick sections than on those with 3-mm-thick sections. CONCLUSION: Our data
      indicate that the acquisition of thinner sections increases the reliability of
      the assessment of changes in brain lesion load on MR images in patients with
      multiple sclerosis.

PMID- 9576655
TI  - Three-dimensional contrast-enhanced MR angiography of the extracranial carotid
      arteries: two techniques.
AB  - Two methods of contrast-enhanced dynamic 3-D MR angiography of the head and neck
      are demonstrated. In the first, arterial and arteriovenous phases are temporally
      resolved by timing contrast injection such that maximum arteriovenous signal
      intensity difference is matched to acquisition of central k-space. A second,
      faster sequence allows for temporal resolution of arterial, early arteriovenous,
      late arteriovenous, and washout arteriovenous phases without a need for precise
      injection timing.

PMID- 9576656
TI  - Velocity-coded color MR angiography.
AB  - We developed a method of velocity-coded color MR angiography using a color code
      from the data obtained from velocity-phase images of phase-contrast MR
      angiography in order to add flow direction information to MR angiograms. Phase
      contrast MR angiography with reconstruction of velocity-phase images was
      performed in 30 patients. Two projection images from velocity-phase images of
      each phase-contrast MR angiogram were obtained and assigned color according to
      flow direction. We then superimposed the two color images onto the maximum
      intensity projection image of the MR angiogram. The velocity-coded color MR
      angiogram clearly showed flow direction from the data on the phase-contrast MR
      angiogram of the neck. Veins were readily distinguishable from arteries, and flow
      changes, such as a subclavian steal, were also identified.

PMID- 9576657
TI  - The size of lymph nodes in the neck on sonograms as a radiologic criterion for
      metastasis: how reliable is it?
AB  - PURPOSE: A definition of cut-off points for nodal size is essential to determine
      whether cervical lymph nodes are metastatic or not. Because the currently used
      size criteria are defined for random populations of patients with head and neck
      cancer, we set out to study whether these criteria are optimal for patients
      without palpable metastases in different levels of the neck We defined optimal
      size criteria for sonography by calculating the sensitivity and specificity of
      different size cut-off points. METHODS: We compared the sensitivity and
      specificity of different size cut-off points as measured on sonograms for various
      levels in the neck in a series of 117 patients with and 131 patients without
      palpable neck metastases. RESULTS: A minimum axial diameter of 7 mm for level II
      and 6 mm for the rest of the neck revealed the optimal compromise between
      sensitivity and specificity in necks without palpable metastases. For all necks
      together (with and without palpable metastases), the criteria were 1 to 2 mm
      larger. CONCLUSION: Our findings indicate that the current sonographic size
      criteria used for random patient populations are not optimal for necks without
      palpable metastases, nor can the same cut-off points be used for all levels in
      the neck.

PMID- 9576658
TI  - Perineural spread of head and neck tumors: how accurate is MR imaging?
AB  - PURPOSE: Our aim was to determine the precision of MR imaging evaluation of
      perineural spread of head and neck tumors. METHODS: Nineteen patients had
      complete extirpation of head and neck tumors (10 squamous cell carcinomas, four
      adenoid cystic carcinomas, one poorly differentiated carcinoma, one salivary duct
      carcinoma, one mucoepidermoid carcinoma, one chordoma, and one meningioma) with
      histologic confirmation of perineural spread. Findings at presurgical contrast
      enhanced MR imaging were compared with findings at pathologic examination.
      RESULTS: The sensitivity of MR imaging for detection of perineural spread was
      95%; however, the sensitivity for mapping the entire extent of perineural spread
      fell to 63%. CONCLUSION: MR imaging may fail to depict microscopic foci of
      perineural tumor infiltration, leading to underestimation of the extent of
      perineural spread. Nevertheless, with careful analysis of foraminal architecture
      and MR enhancement patterns, one can reliably identify the presence if not the
      extent of perineural spread.

PMID- 9576659
TI  - Madelung disease: distribution of cervical fat and preoperative findings at
      sonography, MR, and CT.
AB  - PURPOSE: Our goal was to document the distribution of excess fat in the neck and
      to determine the preoperative role of sonography, CT, and MR imaging in patients
      with Madelung disease. METHODS: Eight patients with Madelung disease were
      examined preoperatively with sonography, CT, and MR imaging of the neck, and the
      extent to which each technique provided answers to the surgeons' questions--such
      as distribution of fat, course of the major vessels within the fat, and presence
      of tracheal compression and nonlipomatous lesions--was studied. RESULTS: Excess
      fat was seen predominantly in the posterior part of the neck (eight patients),
      under the trapezius (eight patients) and sternomastoid (six patients) muscles, in
      the supraclavicular fossa (five patients), between the paraspinal muscles (five
      patients), in the anterior part of the neck (suprahyoid in seven patients and
      infrahyoid in three patients), in the superior mediastinum (three patients), and
      in the prevertebral space (two patients). Excess fat deposition was also seen in
      the pretracheal space (one patient), extrapleural space (two patients), and over
      the cheeks (one patient), sites previously not described. CONCLUSION: As a
      preoperative investigative tool for Madelung disease, both MR imaging and
      noncontrast CT provide the surgeon with adequate information; sonography is less
      helpful.

PMID- 9576660
TI  - CT findings in chondroradionecrosis of the larynx.
AB  - PURPOSE: Our goal was to describe the CT findings before and after radiation
      therapy in a series of patients with laryngeal chondroradionecrosis. METHODS: The
      CT studies obtained before and after radiation therapy in nine patients with the
      diagnosis of laryngeal chondroradionecrosis were reviewed retrospectively.
      RESULTS: CT scans revealed abnormalities in all patients. A variable degree of
      laryngeal soft-tissue swelling was seen in eight of the patients. In four
      patients, cartilaginous abnormalities were visible initially, and appeared in
      three of four other patients who had further follow-up CT studies. Six patients
      had involvement of the thyroid cartilage; collapse of the thyroid cartilage was
      seen in two cases and gas bubbles were visible adjacent to the thyroid cartilage
      in three cases. Four patients with involvement of the thyroid cartilage
      eventually underwent total laryngectomy, and one died suddenly in severe
      respiratory distress. In all three patients with arytenoidal involvement,
      anterior dislocation of this cartilage was seen; in two of these patients, the
      adjacent part of the cricoid cartilage showed some sclerosis. Two patients with
      arytenoidal necrosis (both with cricoidal sclerosis) kept a functional larynx. In
      one case, cricoidal sclerosis was seen in association with lysis of the thyroid
      cartilage. CONCLUSION: The CT appearance of laryngeal chondroradionecrosis is
      nonspecific, but the diagnosis can be strongly suggested in cases of sloughing of
      the arytenoid cartilage, fragmentation and collapse of the thyroid cartilage,
      and/or in the presence of gas bubbles around the cartilage.

PMID- 9576661
TI  - Arytenoid cartilage sclerosis: normal variations and clinical significance.
AB  - PURPOSE: Our purpose was to determine the variation in location, distribution,
      and sex predilection of arytenoid cartilage sclerosis in a population of patients
      without laryngeal cancer as an aid to understanding the significance of this
      entity when seen in patients with laryngeal cancer. METHODS: One hundred CT
      examinations of patients of different ages and with no history of laryngeal
      cancer or radiation therapy were evaluated for the presence of arytenoid
      cartilage sclerosis. The arytenoid cartilage was subdivided into three regions:
      superior process, body, and vocal process. Each region was assessed on each side
      separately on bone window scans. RESULTS: Arytenoid cartilage sclerosis was seen
      in 16% (n = 16) of the patients. Sclerosis was most common in the body (n = 12)
      and least common in the true vocal process (n = 2); the left side was the
      preferred location for all three regions. In 50% of the patients, at least two
      regions were affected. Eighty-one percent of sclerotic arytenoid cartilage was
      seen in women. CONCLUSION: Knowledge of the frequency and distribution of
      arytenoid cartilage sclerosis as a normal variant can aid in determining the risk
      of arytenoid cartilage involvement in patients with laryngeal cancer.

PMID- 9576662
TI  - Malignant lymphoma of the gingiva: MR evaluation.
AB  - PURPOSE: Our purpose was to document the MR imaging findings of malignant
      lymphoma of the gingiva. METHODS: Five patients with histologically proved
      malignant lymphoma of the gingiva were studied by MR imaging. The MR images were
      analyzed for tumor size, extent, and signal characteristics, bone involvement,
      and associated cervical lymph node enlargement. RESULTS: Clinical examination
      tended to underestimate the size of lymphomatous lesions. The signal intensity of
      the lesions was isointense to hyperintense relative to muscle on noncontrast T1
      weighted images and showed variable contrast enhancement patterns. On T2-weighted
      images, signal intensity was isointense to hypointense relative to the oral
      mucosa. In one case, the mass extended to the submandibular space; in the
      remaining cases, the masses were limited to the gingiva and the adjacent bone. MR
      imaging revealed that gingival lymphomatous masses were broad-based along the
      mandible or maxilla and eroded through the cortex into the marrow space, but the
      cortex was still recognizable. No nodal involvement was noted in any of the
      patients with malignant lymphoma. CONCLUSION: The signal characteristics of
      gingival lymphoma overlap those of other tumors. The cortex separating marrow
      involvement from the broad-based gingival mass generally appears to be permeated
      with small erosions but is still recognizable.

PMID- 9576663
TI  - The buccal space: a doorway for percutaneous CT-guided biopsy of the
      parapharyngeal region.
AB  - We performed percutaneous CT-guided needle biopsies with a transfacial approach
      in the diagnosis of lesions of the parapharyngeal region. Via the buccal space,
      core needle biopsy specimens were obtained in eight patients with known
      parapharyngeal abnormalities identified by CT and/or MR imaging. In all cases,
      sufficient tissue was obtained to provide a definitive histologic diagnosis.
      There were no significant complications. This approach provides a reliable method
      for evaluation of parapharyngeal lesions.

PMID- 9576664
TI  - 'Leave me alone' lesions of the petrous apex.
AB  - PURPOSE: When troublesome MR imaging findings are noted in the petrous apex, the
      radiologist must determine if the area in question needs surgical therapy. Two
      nonsurgical entities, asymmetric fatty marrow and fluid-filled petrous air cells
      (trapped fluid), can be noted on conventional brain MR images and confused with
      pathologic lesions. Our observation that radiologists do not always confidently
      define the nonsurgical petrous apex lesions precipitated this investigation.
      METHODS: Twenty-three patients with either asymmetric fatty marrow (six) or
      unilateral effusion in a pneumatized petrous apex (17) on MR images were studied.
      Eighteen patients underwent high-resolution temporal bone CT. For all patients,
      the medical charts were reviewed retrospectively and/or the surgical and clinical
      follow-up findings were reviewed with the referring physician. RESULTS: In the
      patients with asymmetric fatty marrow, MR signal intensity followed fat on all
      sequences. The questioned apex in the patients with trapped fluid showed mixed MR
      signal characteristics (low to high T1 signal, high T2 signal). CT scans
      confirmed nonexpansile air-cell opacification. CONCLUSION: Asymmetric fatty
      marrow in the petrous apex and petrous air-cell effusions have characteristic MR
      and CT features that facilitate their correct diagnosis. Effusions with
      intermediate or high T1 signal are most frequently confused with cholesterol
      granulomas. In those patients, long-term CT follow-up may be helpful to confirm
      their stability.

PMID- 9576665
TI  - Three-dimensional fast spin-echo MR of the inner ear: ultra-long echo train
      length and half-Fourier technique.
AB  - We compared the image quality of the newly developed ultra-long echo train length
      (ETL) 3-D fast spin-echo (FSE) and half-Fourier technique, which is performed in
      less than 3 minutes, with the conventional 3D-FSE imaging technique, which takes
      15 minutes, in assessing MR examinations of the inner ear. The new method's
      images were almost comparable to the conventional 3D-FSE images in depicting
      anatomic details and pathologic findings. Implementation of the ultra-long ETL
      and half-Fourier 3D-FSE imaging technique enables acquisition of inner ear MR
      studies in a vastly reduced time and with high spatial resolution without
      significant penalty, opening the possibility for low-cost screening of acoustic
      tumors without contrast enhancement in less than 3 minutes.

PMID- 9576666
TI  - Terson syndrome: CT evaluation in 12 patients.
AB  - PURPOSE: Terson syndrome may be overlooked in the acute setting and often
      requires ophthalmologic intervention to prevent long-term visual loss. In this
      syndrome, vitreous or retinal hemorrhage results from an abrupt rise in
      intracranial pressure, leading to retinal venous hypertension and intraocular
      hemorrhage. Our objective was to determine whether imaging findings could be
      discovered that might facilitate an earlier diagnosis. METHODS: Our inpatient
      medical record data base for 1991-1996 listed 11 patients with Terson syndrome.
      The medical records of these 11 patients were reviewed retrospectively and
      compared with their noncontrast head CT scans and with scans of 10 control
      subjects. One additional case was discovered prospectively, for a total of 12
      patients. Three radiologists unaware of the patients' history evaluated CT scans
      of the orbits for evidence of intraocular hemorrhage. RESULTS: CT findings in
      eight patients were suggestive of retinal hemorrhage manifested by a retinal
      crescent or nodule that was slightly hyperdense relative to the vitreous humor.
      There was a high degree of concordance between the retrospective and independent
      reviews. CONCLUSION: Retinal nodularity and crescentic hyperdensities are evident
      on CT scans in the majority of patients with Terson syndrome. Although findings
      are subtle and not present in all cases, in the setting of subarachnoid
      hemorrhage they suggest retinal hemorrhage and warrant detailed fundoscopic
      evaluation.

PMID- 9576667
TI  - In vivo CT and MR appearance of prosthetic intraocular lens.
AB  - PURPOSE: We present the first in vivo CT and MR imaging description of
      intraocular lenses (IOLs), which are commonly encountered in elderly patients who
      have undergone cataract surgery. METHODS: A retrospective review was done of the
      imaging studies of 20 patients (22 eyes) with IOLs and of three patients (four
      eyes) with aphakia. CT and MR studies were performed with standard clinical
      protocols. RESULTS: Sixteen patients with 18 posterior IOLs underwent six CT and
      43 MR studies. Four patients with four anterior IOLs had one CT and eight MR
      studies. The exact position of the optic portion of the IOL could be optimally
      determined on CT scans with 1-mm-thick sections and on fat-saturated fast T2
      weighted MR orbital coil studies performed on a 1.5-T imager. The haptics could
      not be distinguished from the ciliary body. Three patients with aphakia had eight
      MR and two CT studies. Aphakia was difficult to identify if the image thickness
      was greater than the diameter of the pupil (2.5 to 4.0 mm). CONCLUSION: The optic
      portion of an IOL is visible on either high-quality CT or MR studies. However,
      the haptic portion is not visible on clinical in vivo images.

PMID- 9576668
TI  - Telangiectatic osteosarcoma of the skull base.
AB  - We present a patient with a distinctive lesion of the skull base, which, at
      imaging, showed expansile destruction of the sphenoid bone, hemorrhage with fluid
      fluid levels, and contrast enhancement of a solid portion. These features
      ordinarily suggest either giant cell tumor or aneurysmal bone cyst; however,
      pathologic examination confirmed instead a rare variant of osteosarcoma of the
      telangiectatic type. Although imaging findings can indicate any of these
      possibilities, biopsy is an essential step in arriving at the diagnosis.

PMID- 9576669
TI  - Transcranial sonographic monitoring during thrombolytic therapy.
AB  - Two patients with acute occlusion of the middle cerebral artery (MCA) were
      treated with intravenous alteplase. Neurovascular monitoring, which was performed
      simultaneously via transcranial sonography, enabled precise documentation of MCA
      recanalization. This information was used to tailor the dosage and duration of
      alteplase treatment. Sonographic information concerning the arterial segments
      involved in the occlusive process, the actual hemodynamic status, and the
      collateral blood supply may help to identify those patients most likely to
      benefit from thrombolysis.

PMID- 9576670
TI  - Why do ulcerated atherosclerotic carotid artery plaques embolize? A flow dynamics
      study.
AB  - PURPOSE: We describe and analyze flow dynamics and pressure relationships in an
      ulcerated atherosclerotic human carotid bulb. METHODS: Replicas of an ulcerated
      atherosclerotic human carotid bulb were created using the lost wax technique. The
      resulting replicas were placed in a circuit of pulsating non-Newtonian fluid and
      flows were adjusted to replicate human physiological flow profiles. Common
      carotid artery total flow volumes of 400, 600, and 800 mL/min were studied.
      Slipstreams were opacified with isobaric dyes. Images were recorded on 35 mm film
      and on super VHS video. A pressure recording device was calibrated; data were
      received from needles placed radially and longitudinally in the common carotid
      artery, narrowed bulb/ulcer, and internal carotid artery. Multiple pressure
      recordings were obtained in the replicas. RESULTS: Measurements of the replica
      showed a 59% diameter stenosis and an 88% area stenosis of the carotid bulb with
      a shallow 3.3-mm ulcer. Analysis of flow in the common carotid artery showed
      undisturbed slipstreams, but as these streams entered the narrowed carotid bulb
      they crowded together and accelerated significantly. This accelerated jet
      continued for at least two vessel diameters into the more normal portions of the
      internal carotid artery, where flow remained disturbed peripherally and often
      assumed a helical pattern but was nonturbulent. As fluid entered the narrowed
      bulb, radial pressures decreased. Most important, at peak systole, lower radial
      pressure with a vortex circulation was found at the ulceration. CONCLUSION: This
      combination of events (ie, slowly swirling fluid within the ulcer, allowing
      platelet aggregates to form, and the intermittent Bernoulli effect, pulling the
      aggregates into the rapidly flowing blood) may help explain how ulcerated carotid
      plaques lead to embolic stroke.

PMID- 9576672
TI  - Preliminary experience with an electrolytically detachable fibered coil.
AB  - We report our preliminary experience with a new embolic device, the
      electrolytically detachable fibered coil, in the treatment of four patients with
      high-flow arteriovenous shunting.

PMID- 9576671
TI  - Direct percutaneous transluminal angioplasty for acute middle cerebral artery
      occlusion.
AB  - PURPOSE: We review our initial experience with direct percutaneous transluminal
      angioplasty (PTA) as a reperfusion treatment for acute occlusion of the middle
      cerebral artery. METHODS: Ten patients in whom successful thrombolysis might not
      be expected because of the risk of hemorrhagic complications or reocclusion were
      treated with direct PTA. When early ischemic findings were present on the initial
      CT scans and/or when lenticulostriate arteries were involved, we performed direct
      PTA rather than thrombolytic therapy. Direct PTA was also performed when
      superselective local angiography via a Tracker catheter advanced just distal to
      the occlusion site showed the presence of a large embolus or high-grade stenosis
      suggestive of thrombosis. Angioplasty was performed with a Stealth balloon
      catheter with a maximum diameter of 2.0 to 2.5 mm. The balloon catheter was
      advanced into the site of occlusion and inflated to 2 atm initially, and
      subsequently up to 3 atm. Two to six inflations, each of 30 seconds' duration,
      were performed. RESULTS: Although the rate of initial recanalization was 100% (10
      of 10), reocclusion occurred in two patients with atherothrombotic M2 occlusion.
      The final angiographic success rate of direct PTA was 80% (8 of 10). There were
      no hemorrhagic or technical complications, and five of 10 patients showed marked
      clinical improvement. In two of seven patients with cardioembolic M1 trunk
      occlusion, crushed fragments of the embolus obstructed M2 portions after direct
      PTA, necessitating local thrombolysis. CONCLUSION: Direct PTA may be performed
      safely as an alternative to thrombolytic therapy in patients with acute occlusion
      of the middle cerebral artery when early CT findings and/or lenticulostriate
      artery involvement are present or when superselective local angiography shows the
      presence of a large embolus or high-grade stenosis.

PMID- 9576673
TI  - Advancing loop technique for endovascular access to the anterior cerebral artery.
AB  - Direct endovascular access to the anterior cerebral artery (ACA) with a guidewire
      and catheter is not always possible. A C-shaped guidewire advanced as a loop into
      the middle cerebral artery and then withdrawn to advance the guidewire into the
      ACA is a way to gain endovascular access to the ACA when the direct approach is
      unsuccessful.

PMID- 9576674
TI  - Recurrent acute transverse myelopathy associated with anticardiolipin antibodies.
AB  - In three patients with recurrent episodes of acute transverse myelopathy, spinal
      MR imaging during each episode showed areas of hyperintensity on proton density-
      and T2-weighted images with inconsistent contrast enhancement. Cranial MR
      imaging, laboratory screenings, and CSF analysis showed only increased titers of
      anticardiolipin antibodies. Although a causative role in neurologic conditions
      has not been established conclusively, an association between these antibodies
      and acute transverse myelopathy and its recurrences cannot be ignored.

PMID- 9576675
TI  - Exophytic primitive neuroectodermal tumor of the spinal cord.
AB  - We present a case of an exophytic spinal primitive neuroectodermal tumor that,
      radiologically, simulated an extramedullary nerve sheath tumor, meningioma, or
      metastatic tumor deposit. MR imaging provided discrete anatomic localization of
      the tumor, enabling exclusion of multicentricity in the brain and spinal cord.

PMID- 9576676
TI  - Atretic parietal cephaloceles revisited: an enlarging clinical and imaging
      spectrum?
AB  - PURPOSE: We describe imaging features that are clues to the diagnosis of atretic
      cephaloceles and discuss clinical findings and a possible mechanism by which
      these lesions develop. METHODS: Eight children (five girls and three boys)
      ranging in age from 1 day to 3 years 4 months with midline subscalp lesions
      underwent radiologic examination with CT or MR imaging. In all cases, the lesions
      were surgically excised and subjected to pathologic examination. Imaging studies
      and medical records were reviewed retrospectively. RESULTS: Six of eight children
      had vertical embryonic positioning of the straight sinus with a prominent
      superior cerebellar cistern. A "spinning-top" configuration of the tentorial
      incisura, a "cigar-shaped" CSF tract within the interhemispheric fissure,
      fenestration of the superior sagittal sinus, and "peaking" of the tentorium were
      associated findings helpful in making this diagnosis. Two of the eight children
      had findings indistinguishable from focal dermoid, six were developmentally
      normal, one had mild motor delay, and one died at the age of 3 years. Pathologic
      examination revealed glial, meningeal (arachnoid), fibrous, and dermal elements.
      CONCLUSION: Characteristic findings on MR images and CT scans provide clues to
      the diagnosis of atretic cephalocele. However, even in the presence of abnormal
      imaging findings, these children may be developmentally normal.

PMID- 9576677
TI  - Neuroimaging in brain death.

PMID- 9576678
TI  - Cervical nodal metastases: another look at size criteria.

PMID- 9576679
TI  - Transcranial Doppler sonography: adding to the toolbox.

PMID- 9576680
TI  - Anticardiolipin antibodies and transverse myelopathy: expanding our understanding
      of an elusive clinical problem.

PMID- 9576681
TI  - The Alzheimer's plaques, tangles and memory deficits may have a common origin;
      part I; a calcium deficit hypothesis.
AB  - Review of the literature reveals that several biochemical events implicated in
      the pathology of Alzheimer's disease (AD) are calcium dependent processes. These
      processes include normal processing of beta-amyloid precursor protein,
      dephosphorylation and degradation of tau, neurotransmitter release and memory
      formation. Since all of these processes appear to be inactivated during
      progression of AD, we propose that a "deficit" of intracellular calcium levels
      may occur in the early phase of the disease. We also propose several experiments
      to test this hypothesis. The hypothesis predicts that presenilins most likely act
      as calcium channels in vivo and that their gene mutations may cause the disease
      by diminishing the Ca2+ channeling function.

PMID- 9576682
TI  - The aging of the NMDA receptor complex.
AB  - N-methyl-D-aspartate (NMDA) receptors are present at high density in the cerebral
      cortex and hippocampus and play an important role in learning and memory. These
      receptors are negatively affected by the aging process, but this effect does not
      appear to be uniform throughout the cortex and hippocampus. This review discusses
      the age-associated changes that occur in the different binding sites of the NMDA
      receptor complex, in the expression of subunits that comprise the complex, in the
      electrophysiological properties of the receptor, and in the ability of NMDA to
      stimulate the release of other transmitters. Spatial memory and some types of
      passive avoidance memory tasks have been shown to involve NMDA receptors. Aged
      animals show deficiencies in the performance of these tasks, as compared to
      young, and some studies have identified an association between lower densities of
      NMDA receptor binding and poor memory performance. A number of drug and diet
      interventions have shown potential for reversing or slowing the effects of aging
      on the NMDA receptor. These studies suggest that the development of treatments
      that are aimed at preventing or reversing the effects of aging on the NMDA
      receptor will aid in preventing the memory declines that are associated with
      aging.

PMID- 9576742
TI  - Can inhibition of apoptosis rescue ischemic brain?

PMID- 9576743
TI  - Stable expression of manganese superoxide dismutase (MnSOD) in insulinoma cells
      prevents IL-1beta- induced cytotoxicity and reduces nitric oxide production.
AB  - The fact that insulin-producing islet beta-cells are susceptible to the cytotoxic
      effects of inflammatory cytokines represents a potential hinderance to the use of
      such cells for transplantation therapy of insulin-dependent diabetes mellitus
      (IDDM). In the current study, we show that IL-1beta induces destruction of INS-1
      insulinoma cells, while having no effect on a second insulinoma cell line RIN1046
      38 and its engineered derivatives, and that this difference is correlated with a
      higher level of expression of manganese superoxide dismutase (MnSOD) in the
      latter cells. Stable overexpression of MnSOD in INS-1 cells provides complete
      protection against IL-1beta-mediated cytotoxicity, and also results in markedly
      reduced killing when such cells are exposed to conditioned media from activated
      human or rat PBMC. Further, overexpression of MnSOD in either RIN- or INS-1
      derived lines results in a sharp reduction in IL-1beta-induced nitric oxide (NO)
      production, a finding that correlates with reduced levels of the inducible form
      of nitric oxide synthase (iNOS). Treatment of INS-1 cells with L-NMMA, an
      inhibitor of iNOS, provides the same degree of protection against IL-1beta or
      supernatants from LPS-activated rat PBMC as MnSOD overexpression, supporting the
      idea that MnSOD protects INS-1 cells by interfering with the normal IL-1beta
      mediated increase in iNOS. Because NO and its derivatives have been implicated as
      critical mediators of beta-cell destruction in IDDM, we conclude that well
      regulated insulinoma cell lines engineered for MnSOD overexpression may be an
      attractive alternative to isolated islets as vehicles for insulin replacement in
      autoimmune diabetes.

PMID- 9576744
TI  - Protection from reoxygenation injury by inhibition of rac1.
AB  - We demonstrate that adenoviral-mediated gene transfer of a dominant negative rac1
      gene product (N17rac1) inhibits the intracellular burst of reactive oxygen
      species (ROS) that occurs after reoxygenation of vascular smooth muscle cells. In
      contrast, expression of a dominant negative ras gene (N17ras) had no effect.
      Challenge of control cells and cells expressing N17rac1 with a direct oxidant
      stress produced an equivalent increase in intracellular ROS levels and subsequent
      cell death. This suggests that N17rac1 expression appears to block production of
      harmful oxygen radicals and does not act directly or indirectly to scavenge ROS
      generated during reoxygenation. Expression of N17rac1 results in protection from
      hypoxia/reoxygenation-induced cell death in a variety of cell types including
      vascular smooth muscle cells, fibroblasts, endothelial cells, and ventricular
      myocytes. These results suggest that reoxygenation injury requires the activation
      of rac proteins, and that inhibition of rac-dependent pathways may be a useful
      strategy for the prevention of reperfusion injury in ischemic tissues.

PMID- 9576745
TI  - Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model
      of chronic renal disease.
AB  - Chronic renal disease (CRD) is generally thought to be incurable, except through
      renal transplantation, and the number of patients with CRD is on the increase.
      Glomerulosclerosis and tubulointerstitial fibrosis represent the morphological
      equivalent of end-stage CRD. In this study, we demonstrated the preventive effect
      of hepatocyte growth factor (HGF) on the progression of renal dysfunction and
      fibrosis, using a spontaneous mouse model for CRD (ICGN strain). The mice
      progressively developed glomerular sclerotic injury, tubular atrophy, and renal
      dysfunction until they were 17 wk of age. When recombinant HGF was injected into
      these mice during a 4-wk-period (from weeks 14-17 after birth), DNA synthesis of
      tubular epithelial cells was found to be 4.4-fold higher than in mice without HGF
      injection, thereby suggesting tubular parenchymal expansion promoted by HGF.
      Notably, HGF suppressed the expression of transforming growth factor-beta and of
      platelet-derived growth factor as well as myofibroblast formation in the affected
      kidney. Consequently, the onset of tubulointerstitial fibrosis was almost
      completely inhibited by HGF, while HGF attenuated the progression of
      glomerulosclerosis, both leading to preventing manifestation of renal
      dysfunction. From our results, supplement therapy with HGF may be taken into
      consideration as a novel option for prevention and treatment of CRD.

PMID- 9576746
TI  - Suppression of graft-versus-host disease and amplification of graft-versus-tumor
      effects by activated natural killer cells after allogeneic bone marrow
      transplantation.
AB  - Bone marrow transplantation (BMT) is currently used for the treatment of a
      variety of neoplastic diseases. However, significant obstacles limiting the
      efficacy of allogeneic BMT are the occurrence of graft-versus-host disease (GvHD)
      and tumor relapse. Natural killer (NK) cells exert a variety of immunologic and
      homoeostatic functions. We examined whether adoptive transfer of activated NK
      cells of donor type would prevent GvHD after allogeneic BMT in mice. Lethally
      irradiated C57BL/6 (H-2(b)) mice, were transplanted with MHC incompatible BALB/c
      (H-2(d)) bone marrow cells and spleen cells and rapidly succumbed to acute GvHD.
      In contrast, mice that also received activated NK cells of donor type exhibited
      significant increases in survival. In determining the mechanism by which the NK
      cells prevented GvHD, mice were concurrently treated with a neutralizing
      antibodies to the immunosuppressive cytokine TGFbeta. Anti-TGFbeta completely
      abrogated the protective effects of the activated donor NK cells indicating that
      TGFbeta plays an important role in the prevention of GvHD by NK cells. We then
      examined whether activated NK cells of donor type after allogeneic BMT would
      induce graft-versus-tumor (GvT) effects without GvHD in mice bearing a murine
      colon adenocarcinoma (MCA-38). 10 d after receiving the tumor, in which the mice
      had demonstrable lung metastases, recipients received an allogeneic BMT with or
      without activated NK cells. Administration of activated NK cells resulted in
      significant GvT effects after allogeneic BMT as evidenced by increases in median
      survival and fewer lung metastasis. No evidence of GVHD was detected compared
      with recipients receiving spleen cells alone which also developed fewer lung
      metastases but in which all had succumbed to GVHD. Thus, our findings suggest
      that adoptive immunotherapy using activated donor NK cells combined with
      allogeneic BMT inhibits GvHD and promotes GvT in advanced tumor-bearing mice.
      These results also suggest that GvT and GvHD can be dissociable phenomena.

PMID- 9576747
TI  - Virulence of catalase-deficient aspergillus nidulans in p47(phox)-/- mice.
      Implications for fungal pathogenicity and host defense in chronic granulomatous
      disease.
AB  - Chronic granulomatous disease (CGD) is a rare genetic disorder in which
      phagocytes fail to produce superoxide because of defects in one of several
      components of the NADPH oxidase complex. As a result, patients develop recurrent
      life-threatening bacterial and fungal infections. The organisms to which CGD
      patients are most susceptible produce catalase, regarded as an important factor
      for microbial pathogenicity in CGD. To test the role of pathogen-derived catalase
      in CGD directly, we have generated isogenic strains of Aspergillus nidulans in
      which one or both of the catalase genes (catA and catB), have been deleted. We
      hypothesized that catalase negative mutants would be less virulent than the wild
      type strain in experimental animal models. CGD mice were produced by disruption
      of the p47(phox) gene which encodes the 47-kD subunit of the NADPH oxidase. Wild
      type A. nidulans inoculated intranasally caused fatal infection in CGD mice, but
      did not cause disease in wild-type littermates. Surprisingly, wild-type A.
      nidulans and the catA, catB, and catA/catB mutants were equally virulent in CGD
      mice. Histopathological studies of fatally infected CGD mice showed widely
      distributed lesions in the lungs regardless of the presence or absence of the
      catA and catB genes. Similar to the CGD model, catalase-deficient A. nidulans was
      highly virulent in cortisone-treated BALB/c mice. Taken together, these results
      indicate that catalases do not play a significant role in pathogenicity of A.
      nidulans in p47(phox)-/- mice, and therefore raise doubt about the central role
      of catalases as a fungal virulence factor in CGD.

PMID- 9576748
TI  - Inhibition of platelet function by recombinant soluble ecto-ADPase/CD39.
AB  - Excessive platelet accumulation and recruitment, leading to vessel occlusion at
      sites of vascular injury, present major therapeutic challenges in cardiovascular
      medicine. Endothelial cell CD39, an ecto-enzyme with ADPase and ATPase
      activities, rapidly metabolizes ATP and ADP released from activated platelets,
      thereby abolishing recruitment. Therefore, a soluble form of CD39, retaining
      nucleotidase activities, would constitute a novel antithrombotic agent. We
      designed a recombinant, soluble form of human CD39, and isolated it from
      conditioned media from transiently transfected COS-1 cells and from stably
      transfected Chinese hamster ovary (CHO) cells. Conditioned medium from CHO cells
      grown under serum-free conditions was subjected to anti-CD39 immunoaffinity
      column chromatography, yielding a single approximately 66-kD protein with ATPase
      and ADPase activities. Purified soluble CD39 blocked ADP-induced platelet
      aggregation in vitro, and inhibited collagen-induced platelet reactivity. Kinetic
      analyses indicated that, while soluble CD39 had a Km for ADP of 5.9 microM and
      for ATP of 2.1 microM, the specificity constant kcat/Km was the same for both
      substrates. Intravenously administered soluble CD39 remained active in mice for
      an extended period of time, with an elimination phase half-life of almost 2 d.
      The data indicate that soluble CD39 is a potential therapeutic agent for
      inhibition of platelet-mediated thrombotic diatheses.

PMID- 9576749
TI  - Pathogen-induced chemokine secretion from model intestinal epithelium is
      inhibited by lipoxin A4 analogs.
AB  - Enteric pathogens induce intestinal epithelium to secrete chemokines that direct
      movement of polymorphonuclear leukocytes. Mechanisms that might downregulate
      secretion of these proinflammatory chemokines and thus contain intestinal
      inflammation have not yet been elucidated. The antiinflammatory activities
      exhibited by the arachidonate metabolite lipoxin A4 (LXA4) suggests that this
      eicosanoid, which is biosynthesized in vivo at sites of inflammation, might play
      such a role. We investigated whether chemokine secretion could be regulated by
      stable analogs of LXA4. Monolayers of T84 intestinal epithelial cells were
      infected with Salmonella typhimurium, which elicits secretion of distinct apical
      (pathogen-elicited epithelial chemoattractant) and basolateral (IL-8) chemokines.
      Stable analogs of LXA4 inhibited S. typhimurium-induced (but not phorbol ester
      induced) secretion of both IL-8 and pathogen-elicited epithelial chemoattractant.
      LXA4 stable analogs did not alter bacterial adherence to nor internalization by
      epithelia, indicating that LXA4 stable analogs did not block all signals that
      Salmonella typhimurium activates in intestinal epithelia, but likely led to
      attenuation of signals that mediate chemokine secretion. Inhibition of S.
      typhimurium-induced IL-8 secretion by LXA4 analogs was concentration- (IC50
      approximately 1 nM) and time-dependent (maximal inhibition approximately 1 h). As
      a result of these effects, LXA4 stable analogs inhibited the ability of bacteria
      infected epithelia to direct polymorphonuclear leukocyte movement. These data
      suggest that LXA4 and its stable analogs may be useful in downregulating active
      inflammation at mucosal surfaces.

PMID- 9576750
TI  - Fatty acid-induced beta cell hypersensitivity to glucose. Increased
      phosphofructokinase activity and lowered glucose-6-phosphate content.
AB  - Diabetic states are characterized by a raised serum/islet level of long chain
      fatty acids and a lowered ED50 for glucose-induced insulin secretion. Prolonged
      culture (> 6 h) of islets with long chain fatty acids replicates the basal
      insulin hypersecretion. We examined this effect in rat islets cultured for 24 h
      with 0.25 mM oleate. Insulin secretion at 2.8 mM glucose was doubled in
      combination with a 60% lowered islet content of glucose-6-phosphate (G6P).
      Investigation of the lowered G6P showed: (a) increased glucose usage from 0.5 to
      100 mM glucose with identical values measured by [2-3H]glucose and [5-3H]glucose,
      (c) indicating little glucose- 6-phosphatase activity, (b) unchanged low pentose
      phosphate shunt activity, (c) 50% increased phosphofructokinase (PFK) Vmax, (d) a
      normal ATP/ADP ratio, and (e) unchanged fructose 2,6 bisphosphate content.
      Triacsin C, an inhibitor of fatty acyl-CoA synthetase, prevented the increase in
      PFK activity and the lowered G6P content. These results suggest that long chain
      acyl-CoA mediates the rise in PFK activity, which in turn lowers the G6P level.
      We speculate that the inhibition of hexokinase by G6P is thus attenuated, thereby
      causing the basal insulin hypersecretion.

PMID- 9576751
TI  - Blockade of CC chemokine receptor 5 (CCR5)-tropic human immunodeficiency virus-1
      replication in human lymphoid tissue by CC chemokines.
AB  - The CC chemokines MIP-1alpha, MIP-1beta, and RANTES suppress replication of
      certain HIV-1 strains in cultured PBMC and T cell lines by blocking interaction
      of gp120 with CC chemokine receptor 5 (CCR5). However, the same chemokines can
      enhance HIV-1 replication in cultured macrophages. The net effect of chemokines
      on HIV-1 infection in intact lymphoid tissue, the major reservoir of HIV-1 in
      vivo, is unknown and unpredictable since the tissue contains both T lymphocytes
      and macrophages. Here we show that exogenous MIP-1alpha, MIP-1beta, and RANTES
      markedly suppressed replication of CCR5-tropic HIV-1 strains in blocks of human
      lymphoid tissue infected ex vivo. Moreover, endogenous MIP-1alpha, MIP-1beta, and
      RANTES were upregulated in tissues infected ex vivo with CXC chemokine receptor 4
      tropic but not CCR5-tropic HIV-1. Such an upregulation may contribute to the
      virus phenotype shift in the course of HIV disease in vivo.

PMID- 9576752
TI  - Bone marrow transplantation prolongs life span and ameliorates neurologic
      manifestations in Sandhoff disease mice.
AB  - The GM2 gangliosidoses are a group of severe, neurodegenerative conditions that
      include Tay-Sachs disease, Sandhoff disease, and the GM2 activator deficiency.
      Bone marrow transplantation (BMT) was examined as a potential treatment for these
      disorders using a Sandhoff disease mouse model. BMT extended the life span of
      these mice from approximately 4.5 mo to up to 8 mo and slowed their neurologic
      deterioration. BMT also corrected biochemical deficiencies in somatic tissues as
      indicated by decreased excretion of urinary oligosaccharides, and lower
      glycolipid storage and increased levels of beta-hexosaminidase activity in
      visceral organs. Even with neurologic improvement, neither clear reduction of
      brain glycolipid storage nor improvement in neuronal pathology could be detected,
      suggesting a complex pathogenic mechanism. Histological analysis revealed beta
      hexosaminidase-positive cells in the central nervous system and visceral organs
      with a concomitant reduction of colloidal iron-positive macrophages. These
      results may be important for the design of treatment approaches for the GM2
      gangliosidoses.

PMID- 9576753
TI  - Evidence for a role of collagen synthesis in arterial smooth muscle cell
      migration.
AB  - Migration of smooth muscle cells (SMCs) and collagen synthesis by SMCs are
      central to the pathophysiology of vascular disease. Both processes can be induced
      shortly after vascular injury; however, a functional relationship between them
      has not been established. In this study, we determined if collagen synthesis was
      required for SMC migration, using ethyl-3,4-dihydroxybenzoate (EDHB), an
      inhibitor of prolyl-4-hydroxylase, and 3,4-DL-dehydroproline (DHP), a proline
      analogue, which we demonstrate inhibit collagen elaboration by porcine arterial
      SMCs. SMCs exposed to EDHB or DHP attached normally to collagen- and vitronectin
      coated substrates; however, spreading on collagen but not vitronectin was
      inhibited. SMC migration speed, quantified by digital time-lapse video
      microscopy, was significantly and reversibly reduced by EDHB and DHP. Flow
      cytometry revealed that expression of beta1 integrins, through which SMCs
      interact with collagen, was unaffected by EDHB or DHP. However, both inhibitors
      prevented normal clustering of beta1 integrins on the surface of SMCs, consistent
      with a lack of appropriate matrix ligands for integrin engagement. Moreover,
      there was impaired recruitment of vinculin into focal adhesion complexes of
      spreading SMCs and disassembly of the smooth muscle alpha-actin-containing
      cytoskeleton. These findings suggest that de novo collagen synthesis plays a role
      in SMC migration and implicates a mechanism whereby newly synthesized collagen
      may be necessary to maintain the transcellular traction system required for
      effective locomotion.

PMID- 9576754
TI  - Tissue factor expression by endothelial cells in sickle cell anemia.
AB  - The role of the vascular endothelium in activation of the coagulation system, a
      fundamental homeostatic mechanism of mammalian biology, is uncertain because
      there is little evidence indicating that endothelial cells in vivo express tissue
      factor (TF), the system's triggering mechanism. As a surrogate for vessel wall
      endothelium, we examined circulating endothelial cells (CEC) from normals and
      patients with sickle cell anemia, a disease associated with activation of
      coagulation. We find that sickle CEC abnormally express TF antigen (expressed as
      percent CEC that are TF-positive), with 66+/-13% positive in sickle patients in
      steady-state, 83+/-19% positive in sickle patients presenting with acute
      vasoocclusive episodes, and only 10+/-13% positive in normal controls. Repeated
      samplings confirmed this impression that TF expression is greater when sickle
      patients develop acute vasoocclusive episodes. Sickle CEC are also positive for
      TF mRNA, with excellent concurrence between antigen and mRNA expression. The TF
      expressed on the antigen-positive CEC is functional, as demonstrated by a binding
      assay for Factor VIIa and a chromogenic assay sensitive to generation of Factor
      Xa. By establishing that endothelial cells in vivo can express TF, these data
      imply that the vast endothelial surface area does provide an important
      pathophysiologic trigger for coagulation activation.

PMID- 9576755
TI  - Leukocyte-endothelial interaction is augmented by high glucose concentrations and
      hyperglycemia in a NF-kB-dependent fashion.
AB  - We addressed the role of hyperglycemia in leukocyte-endothelium interaction under
      flow conditions by exposing human umbilical vein endothelial cells for 24 h to
      normal (5 mM), high concentration of glucose (30 mM), advanced glycosylation end
      product-albumin (100 microg/ml), or hyperglycemic (174-316 mg/dl) sera from
      patients with diabetes and abnormal hemoglobin A1c (8.1+/-1.4%). At the end of
      incubation endothelial cells were perfused with total leukocyte suspension in a
      parallel plate flow chamber under laminar flow (1.5 dyn/cm2). Rolling and
      adherent cells were evaluated by digital image processing. Results showed that 30
      mM glucose significantly (P < 0. 01) increased the number of adherent leukocytes
      to endothelial cells in respect to control (5 mM glucose; 151+/-19 versus 33+/-8
      cells/mm2). A similar response was induced by endothelial stimulation with IL
      1beta, here used as positive control (195+/-20 cells/mm2). The number of rolling
      cells on endothelial surface was not affected by high glucose level. Stable
      adhesion of leukocytes to glucose-treated as well as to IL-1beta-stimulated
      endothelial cells was preceded by short interaction of leukocytes with the
      endothelial surface. The distance travelled by leukocytes before arrest on 30 mM
      glucose, or on IL-1beta-treated endothelial cells, was significantly (P < 0.01)
      higher than that observed for leukocytes adhering on control endothelium (30 mM
      glucose: 76.7+/-3.5; IL1beta: 69.7+/-4 versus 5 mM glucose: 21.5+/-5 microm).
      Functional blocking of E-selectin, intercellular cell adhesion molecule-1, and
      vascular cell adhesion molecule-1 on endothelial cells with the corresponding
      mouse mAb significantly inhibited glucose-induced increase in leukocyte adhesion
      (67+/-16, 83+/-12, 62+/-8 versus 144+/-21 cells/ mm2). Confocal fluorescence
      microscopy studies showed that 30 mM glucose induced an increase in endothelial
      surface expression of E-selectin, intercellular cell adhesion molecule-1, and
      vascular cell adhesion molecule-1. Electrophoretic mobility shift assay of
      nuclear extracts of human umbilical vein endothelial cells (HUVEC) exposed for 1
      h to 30 mM glucose revealed an intense NF-kB activation. Treatment of HUVEC
      exposed to high glucose with the NF-kB inhibitors pyrrolidinedithiocarbamate (100
      microM) and tosyl-phe-chloromethylketone (25 microM) significantly reduced (P <
      0.05) leukocyte adhesion in respect to HUVEC treated with glucose alone. A
      significant (P < 0.01) inhibitory effect on glucose-induced leukocyte adhesion
      was observed after blocking protein kinase C activity with staurosporine (5 nM).
      When HUVEC were treated with specific antisense oligodesoxynucleotides against
      PKCalpha and PKCepsilon isoforms before the addition of 30 mM glucose, a
      significant (P < 0.05) reduction in the adhesion was also seen. Advanced
      glycosylation end product-albumin significantly increased the number of adhering
      leukocytes in respect to native albumin used as control (110+/-16 versus 66+/-7,
      P < 0.01). Sera from diabetic patients significantly (P < 0.01) enhanced
      leukocyte adhesion as compared with controls, despite normal levels of IL-1beta
      and TNFalpha in these sera. These data indicate that high glucose concentration
      and hyperglycemia promote leukocyte adhesion to the endothelium through
      upregulation of cell surface expression of adhesive proteins, possibly depending
      on NF-kB activation.

PMID- 9576756
TI  - Overexpression of myocardial Gsalpha prevents full expression of catecholamine
      desensitization despite increased beta-adrenergic receptor kinase.
AB  - Inotropic and chronotropic responses to catecholamines in young adult transgenic
      mice overexpressing myocardial Gsalpha are enhanced. One might predict that over
      the life of the animal, this chronically enhanced beta-adrenergic receptor
      stimulation would result in homologous catecholamine desensitization. To test
      this hypothesis, old transgenic Gsalpha mice and age-matched controls were
      studied physiologically in terms of responsiveness of left ventricular function
      (ejection fraction) to isoproterenol in vivo and in vitro in terms of beta
      adrenergic receptor signaling. Old transgenic mice still responded to
      isoproterenol with augmented (P < 0.05) left ventricular ejection fraction (+44+/
      3%) compared with age-matched controls (+24+/-1%). Although total beta-adrenergic
      receptor density was reduced in the old transgenic mice, and G protein receptor
      kinase 2 (beta-adrenergic receptor kinase) levels were increased, the fraction of
      receptors binding agonist with high affinity as well as isoproterenol- and G
      protein-stimulated adenylyl cyclase activities were enhanced. Thus, classical
      catecholamine desensitization is not effective in attenuation of persistently
      enhanced responses to sympathetic stimulation in mice overexpressing myocardial
      Gsalpha. To support this conclusion further, experiments were performed with
      chronic isoproterenol, which elicited effective desensitization in wild-type
      controls, but failed to elicit desensitization in overexpressed Gsalpha mice. The
      results of this study suggest that the lack of protective desensitization
      mechanisms may be responsible in part for the dilated cardiomyopathy which
      develops with chronic sympathetic stress over the life of these animals.

PMID- 9576758
TI  - The agent of Human Granulocytic Ehrlichiosis resides in an endosomal compartment.
AB  - The composition of cytoplasmic vacuoles containing the agent of Human
      Granulocytic Ehrlichiosis (HGE) was studied to investigate how this pathogen
      exists within infected host cells. Electron microscopy demonstrated that the HGE
      organism resides in a membrane-bound compartment within HL-60 cells: early forms
      of the HGE agent have a round reticular appearance while later structures are
      small and dense. Vacuoles containing HGE bacteria incorporated endocytosed
      colloidal gold particles, suggesting that they are part of the endocytic pathway.
      Antibodies directed to the mannose-6-phosphate receptor labeled vacuole
      membranes. Antibodies to the transferrin receptor and to the lysosomal membrane
      glycoprotein LAMP 1 did not. Moreover, 3-(2,4-dinitroanilino)-3'-amino-N
      methyldipropylamine, which normally accumulates in compartments with low pH, was
      not present inside these vacuoles. These results suggest that vacuoles containing
      the agent of HGE fail to mature into phagolysosomes. We conclude that the agent
      of HGE appears to enter and modify part of the endocytic pathway.

PMID- 9576757
TI  - Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major
      autoantigen and C3 complement-binding protein in the pathogenesis of multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is characterized by intra-blood-brain barrier
      immunoglobulin synthesis that persists lifelong. Subcellular fractionation and
      two-dimensional electrophoresis were used in conjunction with immune
      precipitation and immunoblotting to identify antigenic determinants for this
      immunoglobulin. We report that 2', 3'-cyclic nucleotide 3'-phosphodiesterase
      (CNP), a protein associated with oligodendrocyte/myelin membranes, also present
      in lymphocytes and retina, is one major target for the humoral response.
      Antibodies to CNP are detected in sera of 74% of MS patients. The antibodies are
      IgM and are present in serum in high titer as well as in cerebrospinal fluid. The
      antibody response is temporally persistent, consistent with systemic immune
      activation and persistent antigenic stimulation. Moreover, CNP is isolated as an
      immune complex from MS brain. CNP is expressed as two isoforms, with CNPII
      identical to CNPI but with a 20-amino acid extension at the amino terminus of
      CNPII; however, the antibody response is exclusively restricted to CNPI. In
      contrast, both isoforms bind the C3 complement, providing a plausible mechanism
      in MS central nervous system (CNS) for opsonization of myelin membrane CNP,
      mediated via the C3 receptor, and phagocytosis of CNP-Ig immune complexes,
      mediated by membrane Ig Fc receptors of macrophages and CNS microglia.

PMID- 9576759
TI  - Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow.
      Evidence for autonomy from factors released during bone resorption.
AB  - Loss of sex steroids causes an increase in both the resorption and formation of
      bone, with the former exceeding the latter. Based on evidence that the increased
      bone resorption after estrogen loss is due to an increase in osteoclastogenesis,
      we hypothesized that estrogen loss also stimulates osteoblastogenesis. We report
      that the number of mesenchymal osteoblast progenitors in the murine bone marrow
      was increased two- to threefold between 2 and 8 wk after ovariectomy and returned
      to control levels by 16 wk. Circulating osteocalcin, as well as
      osteoclastogenesis and the rate of bone loss, followed a very similar temporal
      pattern. Inhibition of bone resorption by administration of the bisphosphonate
      alendronate led to a decrease of the absolute number of osteoblast progenitors;
      however, it did not influence the stimulating effect of ovariectomy on
      osteoblastogenesis or osteoclastogenesis. These observations indicate that the
      increased bone formation that follows loss of estrogen can be explained, at least
      in part, by an increase in osteoblastogenesis. Moreover, they strongly suggest
      that unlike normal bone remodeling, whereby osteoblast development is stimulated
      by factors released from the bone matrix during osteoclastic resorption, estrogen
      deficiency unleashes signals that can stimulate the differentiation of osteoblast
      progenitors in a fashion that is autonomous from the need created by bone
      resorption, and therefore, inappropriate.

PMID- 9576760
TI  - Localization of the apoptosis-inducing activity of lupus anticoagulant in an
      annexin V-binding antibody subset.
AB  - Lupus anticoagulant (LAC) is associated with arterial and venous thrombosis,
      thrombocytopenia, and recurrent fetal loss. We have reported previously that
      plasma with LAC activity induces apoptosis in endothelial cells and binds annexin
      V (Nakamura, N., Y. Shidara, N. Kawaguchi, C. Azuma, N. Mitsuda, S. Onishi, K.
      Yamaji, and Y. Wada. 1994. Biochem. Biophys. Res. Commun. 205:1488-1493). In this
      study, we separated two IgG antibody fractions, one with and one without affinity
      for annexin V, from 10 patients with LAC. LAC and apoptotic activities were
      localized in the annexin V-binding fraction in all 10 patients. DNA fragmentation
      was dose-dependent, paralleling the amount of IgG added to the human umbilical
      vein endothelial cell culture medium, and was inhibited by preincubation with
      annexin V. Removal of the antiphospholipid antibodies from patient IgG with
      phospholipid liposomes did not abolish the apoptosis-inducing activities or
      binding to annexin V. These results imply that patients with LAC often have
      antibodies that do not bind phospholipids and are responsible for the induction
      of apoptosis in endothelial cells.

PMID- 9576761
TI  - Concanavalin A-induced liver injury triggers hepatocyte proliferation.
AB  - Concanavalin A (Con A) injection into mice leads to immune-mediated liver injury.
      We studied whether after Con A-induced liver injury, TNF- and IL-6-dependent
      signaling pathways known to be related to hepatocyte proliferation are activated.
      2 h after Con A injection, maximum TNF-alpha, and after 4-8 h, maximum IL-6 serum
      levels were found. The rise in aminotransferases and DNA fragmentation started
      after 4 h; maximum levels were evident after 8 h. 5-Bromo-2'-deoxyuridine
      staining and nuclear cyclin A expression as markers of the S-phase were first
      detected in hepatocyte nuclei after 24 h, peaking after 48 h. An increase in TNF
      dependent nuclear expression of CCAAT/enhancer-binding protein-beta (C/EBP
      beta)/liver-enriched activating protein (LAP) was detected after 1 h, whereas an
      increase in RNA expression was evident only after 4 h. C/EBP-beta/LAP expression
      returned to normal values before progression into the S-phase. DNA binding of
      signal transducer and activator of transcription (STAT) 3/acute phase response
      factor (APRF) increased for up to 8 h. As found by supershift experiments, in
      addition to STAT3/APRF, STAT1 also binds to the same sequence. During the course
      of time gel shift experiments, DNA binding of the apoptosis-related STAT1 started
      earlier than DNA binding of STAT3/APRF, which regulates hepatocyte proliferation.
      However, the subsequent decrease in DNA binding of both factors was comparable.
      This study demonstrates that after Con A injection, TNF- and IL-6- dependent
      signals trigger nuclear events regulating hepatocyte apoptosis and proliferation
      during liver injury.

PMID- 9576762
TI  - Targeted lung expression of interleukin-11 enhances murine tolerance of 100%
      oxygen and diminishes hyperoxia-induced DNA fragmentation.
AB  - Acute lung injury is a frequent and treatment-limiting consequence of therapy
      with hyperoxic gas mixtures. To determine if IL-11 is protective in oxygen
      toxicity, we compared the effects of 100% O2 on transgenic mice that overexpress
      IL-11 in the lung and transgene (-) controls. IL-11 markedly enhanced survival in
      100% O2 with 100% of transgene (-) animals dying within 72-96 h and > 90% of
      transgene (+) animals surviving for more than 10 d. This protection was
      associated with markedly diminished alveolar-capillary protein leak, endothelial
      and epithelial membrane injury, lipid peroxidation, and pulmonary neutrophil
      recruitment. Significant differences in copper zinc superoxide dismutase and
      catalase activities were not noted and the levels of total, reduced and oxidized
      glutathione were similar in transgene (+) and (-) animals. Glutathione reductase,
      glutathione peroxidase, and manganese superoxide dismutase activities were
      slightly higher in transgene (+) as versus (-) mice after 100% O2 exposure, and
      IL-11 diminished hyperoxia-induced expression of IL-1 and TNF. Hyperoxia also
      caused cell death with DNA fragmentation in the lungs of transgene (-) animals
      and IL-11 markedly diminished this cell death response. These studies demonstrate
      that IL-11 markedly diminishes hyperoxic lung injury. They also demonstrate this
      protection is associated with small changes in lung antioxidants, diminished
      hyperoxia-induced IL-1 and TNF production, and markedly suppressed hyperoxia
      induced DNA fragmentation.

PMID- 9576763
TI  - A targeted point mutation in thrombomodulin generates viable mice with a
      prethrombotic state.
AB  - The activity of the coagulation system is regulated, in part, by the interaction
      of thrombin with the endothelial cell receptor thrombomodulin with subsequent
      generation of activated protein C and suppression of thrombin production. Our
      previous investigation demonstrated that ablation of the thrombomodulin gene in
      mice causes embryonic lethality before the assembly of a functional
      cardiovascular system, indicating a critical role for the receptor in early
      development. In the current study, we show that a single amino acid substitution
      in thrombomodulin dissociates the developmental function of the receptor from its
      role as a regulator of blood coagulation. Homozygous mutant mice with severely
      reduced capacity to generate activated protein C or inhibit thrombin develop to
      term, and possess normal reproductive performance. The above animals exhibit
      increased fibrin deposition in selected organs, which implies tissue specific
      regulation of the coagulation system that is supported by further evidence from
      the examination of mice with defects in fibrinolysis. The thrombomodulin
      deficient animals provide a murine model to examine known or identify unknown
      genetic and environmental factors that lead to the development of thrombosis.

PMID- 9576764
TI  - Caspase inhibitor affords neuroprotection with delayed administration in a rat
      model of neonatal hypoxic-ischemic brain injury.
AB  - Programmed cell death (apoptosis) is a normal process in the developing nervous
      system. Recent data suggest that certain features seen in the process of
      programmed cell death may be favored in the developing versus the adult brain in
      response to different brain injuries. In a well characterized model of neonatal
      hypoxia-ischemia, we demonstrate marked but delayed cell death in which there is
      prominent DNA laddering, TUNEL-labeling, and nuclei with condensed chromatin.
      Caspase activation, which is required in many cases of apoptotic cell death, also
      followed a delayed time course after hypoxia-ischemia. Administration of boc
      aspartyl(OMe)-fluoromethylketone, a pan-caspase inhibitor, was significantly
      neuroprotective when given by intracerebroventricular injection 3 h after
      cerebral hypoxia-ischemia. In addition, systemic injections of boc-aspartyl(OMe)
      fluoromethylketone also given in a delayed fashion, resulted in significant
      neuroprotection. These findings suggest that caspase inhibitors may be able to
      provide benefit over a prolonged therapeutic window after hypoxic-ischemic events
      in the developing brain, a major contributor to static encephalopathy and
      cerebral palsy.

PMID- 9576765
TI  - Exogenous amino acids stimulate net muscle protein synthesis in the elderly.
AB  - We have investigated the response of amino acid transport and protein synthesis
      in healthy elderly individuals (age 71+/-2 yr) to the stimulatory effect of
      increased amino acid availability. Muscle protein synthesis and breakdown, and
      amino acid transport were measured in the postabsorptive state and during the
      intravenous infusion of an amino acid mixture. Muscle-free amino acid kinetics
      were calculated by means of a three compartment model using data obtained by
      femoral arterio-venous catheterization and muscle biopsies from the vastus
      lateralis during the infusion of stable isotope tracers of amino acids. In
      addition, muscle protein fractional synthetic rate (FSR) was measured. Peripheral
      amino acid infusion significantly increased amino acid delivery to the leg, amino
      acid transport, and muscle protein synthesis when measured either with the three
      compartment model (P < 0.05) or with the traditional precursor-product approach
      (FSR increased from 0. 0474+/-0.0054 to 0.0940+/-0.0143%/h, P < 0.05). Because
      protein breakdown did not change during amino acid infusion, a positive net
      balance of amino acids across the muscle was achieved. We conclude that, although
      muscle mass is decreased in the elderly, muscle protein anabolism can nonetheless
      be stimulated by increased amino acid availability. We thus hypothesize that
      muscle mass could be better maintained with an increased intake of protein or
      amino acids.

PMID- 9576766
TI  - A primary malarial infection is composed of a very wide range of genetically
      diverse but related parasites.
AB  - To address the question of how many distinct parasites are injected when a
      mosquito bites, we have characterized isolates resulting most probably from a
      single sporozoite inoculum. We describe the direct and immediate cloning on
      hepatocyte feeder layers of a Thai and an African Plasmodium falciparum primary
      isolate and the characterization of 67 independent clones by four techniques
      totaling nine different markers. This led to three main conclusions: (a) both the
      phenotypic and genotypic markers revealed an unexpectedly large degree of
      diversity within the clones from a single isolate; (b) the clones are nonetheless
      genetically related; and (c) a single mosquito inoculum would most likely be
      sufficient to generate considerable isolate complexity in the absence of repeated
      exposure. This diversity, which has been greatly underestimated in previous
      studies, does not bode well for the development of successful malaria control
      means.

PMID- 9576767
TI  - The C-C chemokine receptor CCR3 participates in stimulation of eosinophil arrest
      on inflammatory endothelium in shear flow.
AB  - Chemokines are widely hypothesized to stimulate firm adhesion of leukocytes on
      endothelium in shear flow. Thus far, this has been demonstrated experimentally
      for exogenously added chemoattractants, but not for those released by
      endothelium. We found that human umbilical cord endothelial cells (HUVEC)
      stimulated with TNF-alpha and IFN-gamma secreted eosinophil chemoattractants into
      the culture supernatant. This material induced transendothelial chemotaxis,
      stimulated eosinophil binding to purified intercellular adhesion molecule 1, and
      augmented binding to purified vascular cell adhesion molecule 1 in a 3-min static
      assay. Chemotaxis and stimulation of adhesion were abrogated completely by the
      pretreatment of eosinophils with an mAb to the C-C chemokine receptor 3 (CCR3).
      Eosinophils accumulated efficiently on HUVEC stimulated with TNF-alpha and IFN
      gamma in shear flow at 1.5 dyn/cm2. CCR3 mAb slightly but significantly reduced
      eosinophil arrest and accumulation, by preventing development of firm adhesion by
      some of the tethered eosinophils, so that they detached within 30 s after the
      initial tethering. In the presence of mAb to the alpha4 integrin subunit, the
      effect of CCR3 mAb was more prominent, and approximately half of eosinophil
      arrest and accumulation was abolished. Inhibition by CCR3 mAb in the presence of
      beta2 integrin mAb was similar to that in control eosinophils. This is the first
      evidence that endothelial cell-derived chemokines can activate firm adhesion
      through alpha4 and beta2 integrins even in the presence of shear flow.

PMID- 9576770
TI  - Aluminum resistance in the Arabidopsis mutant alr-104 is caused by an aluminum
      induced increase in rhizosphere pH.
AB  - A mechanism that confers increased Al resistance in the Arabidopsis thaliana
      mutant alr-104 was investigated. A modified vibrating microelectrode system was
      used to measure H+ fluxes generated along the surface of small Arabidopsis roots.
      In the absence of Al, no differences in root H+ fluxes between wild type and alr
      104 were detected. However, Al exposure induced a 2-fold increase in net H+
      influx in alr-104 localized to the root tip. The increased flux raised the root
      surface pH of alr-104 by 0.15 unit. A root growth assay was used to assess the Al
      resistance of alr-104 and wild type in a strongly pH-buffered nutrient solution.
      Increasing the nutrient solution pH from 4.4 to 4.5 significantly increased Al
      resistance in wild type, which is consistent with the idea that the increased net
      H+ influx can account for greater Al resistance in alr-104. Differences in Al
      resistance between wild type and alr-104 disappeared when roots were grown in pH
      buffered medium, suggesting that Al resistance in alr-104 is mediated only by pH
      changes in the rhizosphere. This mutant provides the first evidence, to our
      knowledge, for an Al-resistance mechanism based on an Al-induced increase in root
      surface pH.

PMID- 9576769
TI  - Aluminum-resistant Arabidopsis mutants that exhibit altered patterns of aluminum
      accumulation and organic acid release from roots.
AB  - Al-resistant (alr) mutants of Arabidopsis thaliana were isolated and
      characterized to gain a better understanding of the genetic and physiological
      mechanisms of Al resistance. alr mutants were identified on the basis of enhanced
      root growth in the presence of levels of Al that strongly inhibited root growth
      in wild-type seedlings. Genetic analysis of the alr mutants showed that Al
      resistance was semidominant, and chromosome mapping of the mutants with
      microsatellite and random amplified polymorphic DNA markers indicated that the
      mutants mapped to two sites in the Arabidopsis genome: one locus on chromosome 1
      (alr-108, alr-128, alr-131, and alr-139) and another on chromosome 4 (alr-104).
      Al accumulation in roots of mutant seedlings was studied by staining with the
      fluorescent Al-indicator dye morin and quantified via inductively coupled argon
      plasma mass spectrometry. It was found that the alr mutants accumulated lower
      levels of Al in the root tips compared with wild type. The possibility that the
      mutants released Al-chelating organic acids was examined. The mutants that mapped
      together on chromosome 1 released greater amounts of citrate or malate (as well
      as pyruvate) compared with wild type, suggesting that Al exclusion from roots of
      these alr mutants results from enhanced organic acid exudation. Roots of alr-104,
      on the other hand, did not exhibit increased release of malate or citrate, but
      did alkalinize the rhizosphere to a greater extent than wild-type roots. A
      detailed examination of Al resistance in this mutant is described in an
      accompanying paper (J. Degenhardt, P.B. Larsen, S.H. Howell, L. V. Kochian [1998]
      Plant Physiol 117: 19-27).

PMID- 9576771
TI  - Phytochrome B affects the levels of a graft-transmissible signal involved in
      tuberization 
AB  - Grafting experiments between phytochrome B antisense and wild-type potato
      (Solanum tuberosum L. subsp. andigena [line 7540]) plants provide evidence that
      phytochrome B is involved in the production of a graft-transmissible inhibitor of
      tuberization, the level of which is reduced in the antisense plants, allowing
      them to tuberize in noninducing photoperiods.

PMID- 9576773
TI  - Expression pattern of the carrot EP3 endochitinase genes in suspension cultures
      and in developing seeds 
AB  - Carrot (Daucus carota) extracellular protein 3 (EP3) class IV endochitinases were
      previously identified based on their ability to rescue somatic embryos of the
      temperature-sensitive cell line ts11. Whole-mount in situ hybridization revealed
      that a subset of the morphologically distinguishable cell types in embryogenic
      and nonembryogenic suspension cultures, including ts11, express EP3 genes. No
      expression was found in somatic embryos. In carrot plants EP3 genes are expressed
      in the inner integumentary cells of young fruits and in a specific subset of
      cells located in the middle of the endosperm of mature seeds. No expression was
      found in zygotic embryos. These results support the hypothesis that the EP3
      endochitinase has a "nursing" function during zygotic embryogenesis and that this
      function can be mimicked by suspension cells during somatic embryogenesis.

PMID- 9576772
TI  - Molecular characterization of the oxalate oxidase involved in the response of
      barley to the powdery mildew fungus.
AB  - Previously we reported that oxalate oxidase activity increases in extracts of
      barley (Hordeum vulgare) leaves in response to the powdery mildew fungus
      (Blumeria [syn. Erysiphe] graminis f.sp. hordei) and proposed this as a source of
      H2O2 during plant-pathogen interactions. In this paper we show that the N
      terminus of the major pathogen-response oxalate oxidase has a high degree of
      sequence identity to previously characterized germin-like oxalate oxidases. Two
      cDNAs were isolated, pHvOxOa, which represents this major enzyme, and pHvOxOb',
      representing a closely related enzyme. Our data suggest the presence of only two
      oxalate oxidase genes in the barley genome, i.e. a gene encoding HvOxOa, which
      possibly exists in several copies, and a single-copy gene encoding HvOxOb. The
      use of 3' end gene-specific probes has allowed us to demonstrate that the HvOxOa
      transcript accumulates to 6 times the level of the HvOxOb transcript in response
      to the powdery mildew fungus. The transcripts were detected in both compatible
      and incompatible interactions with a similar accumulation pattern. The oxalate
      oxidase is found exclusively in the leaf mesophyll, where it is cell wall
      located. A model for a signal transduction pathway in which oxalate oxidase plays
      a central role is proposed for the regulation of the hypersensitive response.

PMID- 9576774
TI  - Family of MADS-Box genes expressed early in male and female reproductive
      structures of monterey pine 
AB  - Three MADS-box genes isolated from Monterey pine (Pinus radiata), PrMADS1,
      PrMADS2, and PrMADS3, are orthologs to members of the AGL2 and AGL6 gene
      subfamilies in Arabidopsis. These genes were expressed during early stages of
      pine shoot development in differentiating seed- and pollen-cone buds. Their
      transcripts were found within a group of cells that formed ovuliferous scale and
      microsporophyll primordia. Expression of PrMADS3 was also detected in a group of
      cells giving rise to needle primordia within differentiated vegetative buds, and
      in needle primordia.

PMID- 9576775
TI  - The diageotropica gene differentially affects auxin and cytokinin responses
      throughout development in tomato.
AB  - The interactions between the plant hormones auxin and cytokinin throughout plant
      development are complex, and genetic investigations of the interdependency of
      auxin and cytokinin signaling have been limited. We have characterized the
      cytokinin sensitivity of the auxin-resistant diageotropica (dgt) mutant of tomato
      (Lycopersicon esculentum Mill.) in a range of auxin- and cytokinin-regulated
      responses. Intact, etiolated dgt seedlings showed cross-resistance to cytokinin
      with respect to root elongation, but cytokinin effects on hypocotyl growth and
      ethylene synthesis in these seedlings were not impaired by the dgt mutation.
      Seven-week-old, green wild-type and dgt plants were also equally sensitive to
      cytokinin with respect to shoot growth and hypocotyl and internode elongation.
      The effects of cytokinin and the dgt mutation on these processes appeared
      additive. In tissue culture organ regeneration from dgt hypocotyl explants showed
      reduced sensitivity to auxin but normal sensitivity to cytokinin, and the effects
      of cytokinin and the mutation were again additive. However, although callus
      induction from dgt hypocotyl explants required auxin and cytokinin, dgt calli did
      not show the typical concentration-dependent stimulation of growth by either
      auxin or cytokinin observed in wild-type cells. Cross-resistance of the dgt
      mutant to cytokinin thus was found to be limited to a small subset of auxin- and
      cytokinin-regulated growth processes affected by the dgt mutation, indicating
      that auxin and cytokinin regulate plant growth through both shared and separate
      signaling pathways.

PMID- 9576776
TI  - A common position-dependent mechanism controls cell-type patterning and GLABRA2
      regulation in the root and hypocotyl epidermis of Arabidopsis.
AB  - A position-dependent pattern of epidermal cell types is produced during root
      development in Arabidopsis thaliana. This pattern is reflected in the expression
      pattern of GLABRA2 (GL2), a homeobox gene that regulates cell differentiation in
      the root epidermis. GL2 promoter::GUS fusions were used to show that the TTG
      gene, a regulator of root epidermis development, is necessary for maximal GL2
      activity but is not required for the pattern of GL2 expression. Furthermore, GL2
      promoter activity is influenced by expression of the myc-like maize R gene
      (35S::R) in Arabidopsis but is not affected by gl2 mutations. A position
      dependent pattern of cell differentiation and GL2-promoter activity was also
      discovered in the hypocotyl epidermis that was analogous to the pattern in the
      root. Non-GL2-expressing cell files in the hypocotyl epidermis located outside
      anticlinal cortical cell walls exhibit reduced cell length and form stomata. Like
      the root, the hypocotyl GL2 activity was shown to be influenced by ttg and 35S::R
      but not by gl2. The parallel pattern of cell differentiation in the root and
      hypocotyl indicates that TTG and GL2 participate in a common position-dependent
      mechanism to control cell-type patterning throughout the apical-basal axis of the
      Arabidopsis seedling.

PMID- 9576777
TI  - Tomato fructokinases exhibit differential expression and substrate regulation 
AB  - Two divergent genes encoding fructokinase, Frk1 and Frk2, have been previously
      shown to be expressed in tomato (Lycopersicon esculentum L.) and have now been
      further characterized with regard to their spatial expression and the enzymic
      properties of the encoded proteins. Frk1 and Frk2 mRNA levels were coordinately
      induced by exogenous sugar, indicating that both belong to the growing class of
      sugar-regulated genes. However, in situ hybridization indicated that Frk1 and
      Frk2 were expressed in a spatially distinct manner, with Frk2 mRNA primarily
      localized in cells of the fruit pericarp, which store starch, and Frk1 mRNA
      distributed ubiquitously in pericarp tissue. To evaluate the biochemical
      characteristics of the products of the Frk1 and Frk2 genes, each cDNA was
      expressed in a mutant yeast (Saccharomyces cerevisiae) line defective in hexose
      phosphorylation and unable to grow on glucose or fructose (Fru). Both Frk1 and
      Frk2 proteins expressed in yeast conferred the ability to grow on Fru and
      exhibited fructokinase activity in vitro. Although both Frk1 and Frk2 both
      utilized Fru as a substrate, only Frk2 activity was inhibited at high Fru
      concentrations. These results indicate that Frk2 can be distinguished from Frk1
      by its sensitivity to substrate inhibition and by its temporal and spatial
      pattern of expression, which suggests that it plays a primary role in plant cells
      specialized for starch storage.

PMID- 9576778
TI  - Tomato flower abnormalities induced by low temperatures are associated with
      changes of expression of MADS-Box genes 
AB  - Flower and fruit development in tomato (Lycopersicon esculentum Mill. ) were
      severely affected when plants were grown at low temperatures, displaying homeotic
      and meristic transformations and alterations in the fusion pattern of the organs.
      Most of these homeotic transformations modified the identity of stamens and
      carpels, giving rise to intermediate organs. Complete homeotic transformations
      were rarely found and always affected organs of the reproductive whorls. Meristic
      transformations were also commonly observed in the reproductive whorls, which
      developed with an excessive number of organs. Scanning electron microscopy
      revealed that meristic transformations take place very early in the development
      of the flower and are related to a significant increase in the floral meristem
      size. However, homeotic transformations should occur later during the development
      of the organ primordia. Steady-state levels of transcripts corresponding to
      tomato MADS-box genes TM4, TM5, TM6, and TAG1 were greatly increased by low
      temperatures and could be related to these flower abnormalities. Moreover, in
      situ hybridization analyses showed that low temperatures also altered the stage
      specific expression of TM4.

PMID- 9576779
TI  - Suppression of O-methyltransferase gene by homologous sense transgene in quaking
      aspen causes red-brown wood phenotypes 
AB  - Homologous sense suppression of a gene encoding lignin pathway caffeic acid O
      methyltransferase (CAOMT) in the xylem of quaking aspen (Populus tremuloides
      Michx.) resulted in transgenic plants exhibiting novel phenotypes with either
      mottled or complete red-brown coloration in their woody stems. These phenotypes
      appeared in all independent transgenic lines regenerated with a sense CAOMT
      construct but were absent from all plants produced with antisense CAOMT. The
      CAOMT sense transgene expression was undetectable, and the endogenous CAOMT
      transcript levels and enzyme activity were reduced in the xylem of some
      transgenic lines. In contrast, the sense transgene conferred overexpression of
      CAOMT and significant CAOMT activity in all of the transgenic plants' leaves and
      sclerenchyma, where normally the expression of the endogenous CAOMT gene is
      negligible. Thus, our results support the notion that the occurrence of sense
      cosuppression depends on the degree of sequence homology and endogene expression.
      Furthermore, the suppression of CAOMT in the xylem resulted in the incorporation
      of a higher amount of coniferyl aldehyde residues into the lignin in the wood of
      the sense plants. Characterization of the lignins isolated from these transgenic
      plants revealed that a high amount of coniferyl aldehyde is the origin of the red
      brown coloration-a phenotype correlated with CAOMT-deficient maize (Zea mays L.)
      brown-midrib mutants.

PMID- 9576780
TI  - Indole-3-acetic acid controls cambial growth in scots pine by positional
      signaling 
AB  - The vascular cambium produces secondary xylem and phloem in plants and is
      responsible for wood formation in forest trees. In this study we used a
      microscale mass-spectrometry technique coupled with cryosectioning to visualize
      the radial concentration gradient of endogenous indole-3-acetic acid (IAA) across
      the cambial meristem and the differentiating derivatives in Scots pine (Pinus
      sylvestris L.) trees that had different rates of cambial growth. This approach
      allowed us to investigate the relationship between growth rate and the
      concentration of endogenous IAA in the dividing cells. We also tested the
      hypothesis that IAA is a positional signal in xylem development (C. Uggla, T.
      Moritz, G. Sandberg, B. Sundberg [1996] Proc Natl Acad Sci USA 93: 9282-9286).
      This idea postulates that the width of the radial concentration gradient of IAA
      regulates the radial number of dividing cells in the cambial meristem, which is
      an important component for determining cambial growth rate. The relationship
      between IAA concentration in the dividing cells and growth rate was poor,
      although the highest IAA concentration was observed in the fastest-growing
      cambia. The radial width of the IAA concentration gradient showed a strong
      correlation with cambial growth rate. The results indicate that IAA gives
      positional information in plants.

PMID- 9576781
TI  - Cytochrome P450 monooxygenases for fatty acids and xenobiotics in marine
      macroalgae.
AB  - The metabolism of xenobiotics has mainly been investigated in higher plant
      species. We studied them in various marine macroalgae of the phyla Chlorophyta,
      Chromophyta, and Rhodophyta. Microsomes contained high oxidative activities for
      known cytochrome (Cyt) P450 substrates (fatty acids, cinnamic acid, 3- and 4
      chlorobiphenyl, 2, 3-dichlorobiphenyl, and isoproturon; up to 54 pkat/mg
      protein). The presence of Cyt P450 (approximately 50 pmol/mg protein) in
      microsomes of the three algal families was demonstrated by CO-difference
      absorption spectra. Intact algal tissue converted 3-chlorobiphenyl to the same
      monohydroxy-metabolite formed in vitro. This conversion was 5-fold stimulated
      upon addition of phenobarbital, and was abolished by the known P450 inhibitor, 1
      aminobenzotriazole. It is concluded that marine macroalgae contain active species
      of Cyt P450 and could act as a metabolic sink for marine pollutants.

PMID- 9576782
TI  - The regulation of photosynthetic electron transport during nutrient deprivation
      in Chlamydomonas reinhardtii.
AB  - The light-saturated rate of photosynthetic O2 evolution in Chlamydomonas
      reinhardtii declined by approximately 75% on a per-cell basis after 4 d of P
      starvation or 1 d of S starvation. Quantitation of the partial reactions of
      photosynthetic electron transport demonstrated that the light-saturated rate of
      photosystem (PS) I activity was unaffected by P or S limitation, whereas light
      saturated PSII activity was reduced by more than 50%. This decline in PSII
      activity correlated with a decline in both the maximal quantum efficiency of PSII
      and the accumulation of the secondary quinone electron acceptor of PSII
      nonreducing centers (PSII centers capable of performing a charge separation but
      unable to reduce the plastoquinone pool). In addition to a decline in the light
      saturated rate of O2 evolution, there was reduced efficiency of excitation energy
      transfer to the reaction centers of PSII (because of dissipation of absorbed
      light energy as heat and because of a transition to state 2). These findings
      establish a common suite of alterations in photosynthetic electron transport that
      results in decreased linear electron flow when C. reinhardtii is limited for
      either P or S. It was interesting that the decline in the maximum quantum
      efficiency of PSII and the accumulation of the secondary quinone electron
      acceptor of PSII nonreducing centers were regulated specifically during S-limited
      growth by the SacI gene product, which was previously shown to be critical for
      the acclimation of C. reinhardtii to S limitation (J.P. Davies, F.H. Yildiz, and
      A.R. Grossman [1996] EMBO J 15: 2150-2159).

PMID- 9576783
TI  - Characterization of recombinant rhamnogalacturonan alpha-L-rhamnopyranosyl-(1,4)
      alpha-D-galactopyranosyluronide lyase from Aspergillus aculeatus. An enzyme that
      fragments rhamnogalacturonan I regions of pectin.
AB  - The four major oligomeric reaction products from saponified modified hairy
      regions (MHR-S) from apple, produced by recombinant rhamnogalacturonan (RG) alpha
      L-rhamnopyranosyl-(1, 4)-alpha-D-galactopyranosyluronide lyase (rRG-lyase) from
      Aspergillus aculeatus, were isolated and characterized by 1H-nuclear magnetic
      resonance spectroscopy. They contain an alternating RG backbone with a degree of
      polymerization of 4, 6, 8, and 10 and with an alpha-Delta-(4,5)-unsaturated D
      galactopyranosyluronic acid at the nonreducing end and an L-rhamnopyranose at the
      reducing end. L-Rhamnopyranose units are substituted at C-4 with beta-galactose.
      The maximum reaction rate of rRG-lyase toward MHR-S at pH 6.0 and 31 degreesC was
      28 units mg-1. rRG-lyase and RG-hydrolase cleave the same alternating RG I
      subunit in MHR. Both of these enzymes fragment MHR by a multiple attack
      mechanism. The catalytic efficiency of rRG-lyase for MHR increases with
      decreasing degree of acetylation. Removal of arabinose side chains improves the
      action of rRG-lyase toward MHR-S. In contrast, removal of galactose side chains
      decreased the catalytic efficiency of rRG-lyase. Native RG-lyase was purified
      from A. aculeatus, characterized, and found to be similar to the rRG-lyase
      expressed in Aspergillus oryzae.

PMID- 9576784
TI  - Rhamnogalacturonan alpha-d-galactopyranosyluronohydrolase. An enzyme that
      specifically removes the terminal nonreducing galacturonosyl residue in
      rhamnogalacturonan regions of pectin 
AB  - A new enzyme, rhamnogalacturonan (RG) alpha-d-galactopyranosyluronohydrolase (RG
      galacturonohydrolase), able to release a galacturonic acid residue from the
      nonreducing end of RG chains but not from homogalacturonan, was purified from an
      Aspergillus aculeatus enzyme preparation. RG-galacturonohydrolase acted with
      inversion of anomeric configuration, initially releasing beta-d
      galactopyranosyluronic acid. The enzyme cleaved smaller RG substrates with the
      highest catalytic efficiency. A Michaelis constant of 85 &mgr;m and a maximum
      reaction rate of 160 units mg-1 was found toward a linear RG fragment with a
      degree of polymerization of 6. RG-galacturonohydrolase had a molecular mass of 66
      kD, an isoelectric point of 5.12, a pH optimum of 4.0, and a temperature optimum
      of 50 degreesC. The enzyme was most stable between pH 3.0 and 6.0 (for 24 h at 40
      degreesC) and up to 60 degreesC (for 3 h).

PMID- 9576785
TI  - Galactosylononitol and stachyose synthesis in seeds of adzuki bean. Purification
      and characterization of stachyose synthase.
AB  - Stachyose synthase (STS) (EC 2.4.1.67) was purified to homogeneity from mature
      seeds of adzuki bean (Vigna angularis). Electrophoresis under denaturing
      conditions revealed a single polypeptide of 90 kD. Size-exclusion chromatography
      of the purified enzyme yielded two activity peaks with apparent molecular masses
      of 110 and 283 kD. By isoelectric focusing and chromatofocusing the protein was
      separated into several active forms with isoelectric point values between pH 4. 7
      and 5.0. Purified STS catalyzed the transfer of the galactosyl group from
      galactinol to raffinose and myo-inositol. Additionally, the enzyme catalyzed the
      galactinol-dependent synthesis of galactosylononitol from D-ononitol. The
      synthesis of a galactosylcyclitol by STS is a new oberservation. Mutual
      competitive inhibition was observed when the enzyme was incubated with both
      substrates (raffinose and ononitol) simultaneously. Galactosylononitol could also
      substitute for galactinol in the synthesis of stachyose from raffinose. Although
      galactosylononitol was the less-efficient donor, the Michaelis constant value for
      raffinose was lower in the presence of galactosylononitol (13.2 mm) compared with
      that obtained in the presence of galactinol (38.6 mm). Our results indicate that
      STS catalyzes the biosynthesis of galactosylononitol, but may also mediate a
      redistribution of galactosyl residues from galactosylononitol to stachyose.

PMID- 9576786
TI  - Ultraviolet-B radiation effects on water relations, leaf development, and
      photosynthesis in droughted pea plants 
AB  - The effects of ultraviolet-B (UV-B) radiation on water relations, leaf
      development, and gas-exchange characteristics in pea (Pisum sativum L. cv Meteor)
      plants subjected to drought were investigated. Plants grown throughout their
      development under a high irradiance of UV-B radiation (0.63 W m-2) were compared
      with those grown without UV-B radiation, and after 12 d one-half of the plants
      were subjected to 24 d of drought that resulted in mild water stress. UV-B
      radiation resulted in a decrease of adaxial stomatal conductance by approximately
      65%, increasing stomatal limitation of CO2 uptake by 10 to 15%. However, there
      was no loss of mesophyll light-saturated photosynthetic activity. Growth in UV-B
      radiation resulted in large reductions of leaf area and plant biomass, which were
      associated with a decline in leaf cell numbers and cell division. UV-B radiation
      also inhibited epidermal cell expansion of the exposed surface of leaves. There
      was an interaction between UV-B radiation and drought treatments: UV-B radiation
      both delayed and reduced the severity of drought stress through reductions in
      plant water-loss rates, stomatal conductance, and leaf area.

PMID- 9576787
TI  - Fruit development in trillium. Dependence On stem carbohydrate reserves 
AB  - Leaves are the main source of carbon for fruit maturation in most species.
      However, in plants seeing contrasting light conditions such as some spring
      plants, carbon fixed during the spring could be used to support fruit development
      in the summer, when photosynthetic rates are low. We monitored carbohydrate
      content in the rhizome (a perennating organ) and the aboveground stem of trillium
      (Trillium erectum) over the entire growing season (May-November). At the
      beginning of the fruiting stage, stems carrying a developing fruit were
      harvested, their leaves were removed, and the leafless stems were maintained in
      aqueous solution under controlled conditions up to full fruit maturation. These
      experiments showed that stem carbohydrate content was sufficient to support fruit
      development in the absence of leaves and rhizome. This is the first reported
      case, to our knowledge, of complete fruit development sustained only by a
      temporary carbohydrate reservoir. This carbohydrate accumulation in the stem
      during the spring enables the plant to make better use of the high irradiances
      occurring at that time. Many other species might establish short-term
      carbohydrate reservoirs in response to seasonal changes in growing conditions.

PMID- 9576788
TI  - Light-regulated transcription of genes encoding peridinin chlorophyll a proteins
      and the major intrinsic light-harvesting complex proteins in the dinoflagellate
      amphidinium carterae hulburt (Dinophycae). Changes In cytosine methylation
      accompany photoadaptation 
AB  - In the dinoflagellate Amphidinium carterae, photoadaptation involves changes in
      the transcription of genes encoding both of the major classes of light-harvesting
      proteins, the peridinin chlorophyll a proteins (PCPs) and the major a/c
      containing intrinsic light-harvesting proteins (LHCs). PCP and LHC transcript
      levels were increased up to 86- and 6-fold higher, respectively, under low-light
      conditions relative to cells grown at high illumination. These increases in
      transcript abundance were accompanied by decreases in the extent of methylation
      of CpG and CpNpG motifs within or near PCP- and LHC-coding regions. Cytosine
      methylation levels in A. carterae are therefore nonstatic and may vary with
      environmental conditions in a manner suggestive of involvement in the regulation
      of gene expression. However, chemically induced undermethylation was insufficient
      in activating transcription, because treatment with two methylation inhibitors
      had no effect on PCP mRNA or protein levels. Regulation of gene activity through
      changes in DNA methylation has traditionally been assumed to be restricted to
      higher eukaryotes (deuterostomes and green plants); however, the atypically large
      genomes of dinoflagellates may have generated the requirement for systems of this
      type in a relatively "primitive" organism. Dinoflagellates may therefore provide
      a unique perspective on the evolution of eukaryotic DNA-methylation systems.

PMID- 9576789
TI  - Purification and characterization of a low-molecular-weight phospholipase A2 from
      developing seeds of elm.
AB  - Phospholipase A2 (PLA2) was purified about 180,000 times compared with the
      starting soluble-protein extract from developing elm (Ulmus glabra) seeds. On
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis the purified fraction
      showed a single protein band with a mobility that corresponded to 15 kD, from
      which activity could be recovered. When analyzed by matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry, the enzyme had a deduced
      mass of 13,900 D. A 53-amino acid-long N-terminal sequence was determined and
      aligned with other sequences, giving 62% identity to the deduced amino acid
      sequence of some rice (Oryza sativa) expressed sequence tag clones. The purified
      enzyme had an alkaline pH optimum and required Ca2+ for activity. It was
      unusually stable with regard to heat, acidity, and organic solvents but was
      sensitive to disulfide bond-reducing agents. The enzyme is a true PLA2, neither
      hydrolyzing the sn-1 position of phosphatidylcholine nor having any activity
      toward lysophosphatidylcholine or diacylglycerol. The biochemical data and amino
      acid sequence alignments indicate that the enzyme is related to the well
      characterized family of animal secretory PLA2s and, to our knowledge, is the
      first plant enzyme of this type to be described.

PMID- 9576790
TI  - Estimating photosynthesis and concurrent export rates in C3 and C4 species at
      ambient and elevated CO21,2 
AB  - The ability of 21 C3 and C4 monocot and dicot species to rapidly export newly
      fixed C in the light at both ambient and enriched CO2 levels was compared.
      Photosynthesis and concurrent export rates were estimated during isotopic
      equilibrium of the transport sugars using a steady-state 14CO2-labeling
      procedure. At ambient CO2 photosynthesis and export rates for C3 species were 5
      to 15 and 1 to 10 &mgr;mol C m-2 s-1, respectively, and 20 to 30 and 15 to 22
      &mgr;mol C m-2 s-1, respectively, for C4 species. A linear regression plot of
      export on photosynthesis rate of all species had a correlation coefficient of
      0.87. When concurrent export was expressed as a percentage of photosynthesis,
      several C3 dicots that produced transport sugars other than Suc had high efflux
      rates relative to photosynthesis, comparable to those of C4 species. At high CO2
      photosynthetic and export rates were only slightly altered in C4 species, and
      photosynthesis increased but export rates did not in all C3 species. The C3
      species that had high efflux rates relative to photosynthesis at ambient CO2
      exported at rates comparable to those of C4 species on both an absolute basis and
      as a percentage of photosynthesis. At ambient CO2 there were strong linear
      relationships between photosynthesis, sugar synthesis, and concurrent export.
      However, at high CO2 the relationships between photosynthesis and export rate and
      between sugar synthesis and export rate were not as strong because sugars and
      starch were accumulated.

PMID- 9576791
TI  - Two structurally similar maize cytosolic superoxide dismutase genes, Sod4 and
      Sod4A, respond differentially to abscisic acid and high osmoticum.
AB  - The maize (Zea mays) superoxide dismutase genes Sod4 and Sod4A are highly similar
      in structure but each responds differentially to environmental signals. We
      examined the effects of the hormone abscisic acid (ABA) on the developmental
      response of Sod4 and Sod4A. Although both Sod4 and Sod4A transcripts accumulate
      during late embryogenesis, only Sod4 is up-regulated by ABA and osmotic stress.
      Accumulation of Sod4 transcript in response to osmotic stress is a consequence of
      increased endogenous ABA levels in developing embryos. Sod4 mRNA is up-regulated
      by ABA in viviparous-1 mutant embryos. Sod4 transcript increases within 4 h with
      ABA not only in developing embryos but also in mature embryos and in young
      leaves. Sod4A transcript is up-regulated by ABA only in young leaves, but neither
      Sod4 nor Sod4A transcripts changed in response to osmotic stress. Our data
      suggest that in leaves Sod4 and Sod4A may respond to ABA and osmotic stress via
      alternate pathways. Since the Sod genes have a known function, we hypothesize
      that the increase in Sod mRNA in response to ABA is due in part to ABA-mediated
      metabolic changes leading to changes in oxygen free radical levels, which in turn
      lead to the induction of the antioxidant defense system.

PMID- 9576792
TI  - Transcriptional and posttranscriptional control of mRNA from lrtA, a light
      repressed transcript in Synechococcus sp. PCC 7002.
AB  - Transcription regulation and transcript stability of a light-repressed
      transcript, lrtA, from the cyanobacterium Synechococcus sp. PCC 7002 were studied
      using ribonuclease protection assays. The transcript for lrtA was not detected in
      continuously illuminated cells, yet transcript levels increased when cells were
      placed in the dark. A lag of 20 to 30 min was seen in the accumulation of this
      transcript after the cells were placed in the dark. Transcript synthesis
      continued in the dark for 3 h and the transcript levels remained elevated for at
      least 7 h. The addition of 10 microM rifampicin to illuminated cells before dark
      adaptation inhibited the transcription of lrtA in the dark. Upon the addition of
      rifampicin to 3-h dark-adapted cells, lrtA transcript levels remained constant
      for 30 min and persisted for 3 h. A 3-h half-life was estimated in the dark,
      whereas a 4-min half-life was observed in the light. Extensive secondary
      structure was predicted for this transcript within the 5' untranslated region,
      which is also present in the 5' untranslated region of lrtA from a different
      cyanobacterium, Synechocystis sp. PCC 6803. Evidence suggests that lrtA
      transcript stability is not the result of differences in ribonuclease activity
      from dark to light. Small amounts of lrtA transcript were detected in illuminated
      cells upon the addition of 25 microg mL-1 chloramphenicol. The addition of
      chloramphenicol to dark-adapted cells before illumination allowed detection of
      the lrtA transcript for longer times in the light relative to controls without
      chloramphenicol. These results suggest that lrtA mRNA processing in the light is
      different from that in the dark and that protein synthesis is required for light
      repression of the lrtA transcript.

PMID- 9576793
TI  - Association of ferredoxin-NADP oxidoreductase with the chloroplastic pyridine
      nucleotide dehydrogenase complex in barley leaves 
AB  - Barley (Hordeum vulgare L.) leaves were used to isolate and characterize the
      chloroplast NAD(P)H dehydrogenase complex. The stroma fraction and the thylakoid
      fraction solubilized with sodium deoxycholate were analyzed by native
      polyacrylamide gel electrophoresis, and the enzymes detected with NADH and
      nitroblue tetrazolium were electroeluted. The enzymes electroeluted from band S
      from the stroma fraction and from bands T1 (ET1) and T2 from the thylakoid
      fraction solubilized with sodium deoxycholate had ferredoxin-NADP oxidoreductase
      (FNR; EC 1.18.1.2) and NAD(P)H-FeCN oxidoreductase (NAD[P]H-FeCNR) activities.
      Their NADPH-FeCNR activities were inhibited by 2'-monophosphoadenosine-5'
      diphosphoribose and by enzyme incubation with p-chloromercuriphenylsulfonic acid
      (p-CMPS), NADPH, and p-CMPS plus NADPH. They presented Michaelis constant NADPH
      values that were similar to those of FNRs from several sources. Their NADH-FeCNR
      activities, however, were not inhibited by 2'-monophosphoadenosine-5'
      diphosphoribose but were weakly inhibited by enzyme incubation with NADH, p-CMPS,
      and p-CMPS plus NADH. We found that only ET1 contained two polypeptides of 29 and
      35 kD, which reacted with the antibodies raised against the mitochondrial complex
      I TYKY subunit and the chloroplast ndhA gene product, respectively. However, all
      three enzymes contained two polypeptides of 35 and 53 kD, which reacted with the
      antibodies raised against barley FNR and the NADH-binding 51-kD polypeptide of
      the mitochondrial complex I, respectively. The results suggest that ET1 is the
      FNR-containing thylakoidal NAD(P)H dehydrogenase complex.

PMID- 9576795
TI  - Substrate specificity of barley cysteine endoproteases EP-A and EP-B.
AB  - The cysteine endoproteases (EP)-A and EP-B were purified from green barley
      (Hordeum vulgare L.) malt, and their identity was confirmed by N-terminal amino
      acid sequencing. EP-B cleavage sites in recombinant type-C hordein were
      determined by N-terminal amino acid sequencing of the cleavage products, and were
      used to design internally quenched, fluorogenic peptide substrates. Tetrapeptide
      substrates of the general formula 2-aminobenzoyl-P2-P1-P1'-P2'-tyrosine(NO2)
      aspartic acid, in which cleavage occurs between P1 and P1', showed that the
      cysteine EPs preferred phenylalanine, leucine, or valine at P2. Arginine was
      preferred to glutamine at P1, whereas proline at P2, P1, or P1' greatly reduced
      substrate kinetic specificity. Enzyme cleavage of C hordein was mainly determined
      by the primary sequence at the cleavage site, because elongation of substrates,
      based on the C hordein sequence, did not make them more suitable substrates. Site
      directed mutagenesis of C hordein, in which serine or proline replaced leucine,
      destroyed primary cleavage sites. EP-A and EP-B were both more active than
      papain, mostly because of their much lower Km values.

PMID- 9576794
TI  - Cloning, expression in Escherichia coli, and characterization of Arabidopsis
      thaliana UMP/CMP kinase.
AB  - A cDNA encoding the Arabidopsis thaliana uridine 5'-monophosphate (UMP)/cytidine
      5'-monophosphate (CMP) kinase was isolated by complementation of a Saccharomyces
      cerevisiae ura6 mutant. The deduced amino acid sequence of the plant UMP/CMP
      kinase has 50% identity with other eukaryotic UMP/CMP kinase proteins. The cDNA
      was subcloned into pGEX-4T-3 and expressed as a glutathione S-transferase fusion
      protein in Escherichia coli. Following proteolytic digestion, the plant UMP/CMP
      kinase was purified and analyzed for its structural and kinetic properties. The
      mass, N-terminal sequence, and total amino acid composition agreed with the
      sequence and composition predicted from the cDNA sequence. Kinetic analysis
      revealed that the UMP/CMP kinase preferentially uses ATP (Michaelis constant [Km]
      = 29 microM when UMP is the other substrate and Km = 292 microM when CMP is the
      other substrate) as a phosphate donor. However, both UMP (Km = 153 microM) and
      CMP (Km = 266 microM) were equally acceptable as the phosphate acceptor. The
      optimal pH for the enzyme is 6.5. P1, P5-di(adenosine-5') pentaphosphate was
      found to be a competitive inhibitor of both ATP and UMP.

PMID- 9576796
TI  - Isolation of the ornithine-delta-aminotransferase cDNA and effect of salt stress
      on its expression in Arabidopsis thaliana.
AB  - To evaluate the relative importance of ornithine (Orn) as a precursor in proline
      (Pro) synthesis, we isolated and sequenced a cDNA encoding the Orn-delta
      aminotransferase (delta-OAT) from Arabidopsis thaliana. The deduced amino acid
      sequence showed high homology with bacterial, yeast, mammalian, and plant
      sequences, and the N-terminal residues exhibited several common features with a
      mitochondrial transit peptide. Our results show that under both salt stress and
      normal conditions, delta-OAT activity and mRNA in young plantlets are slightly
      higher than in older plants. This appears to be related to the necessity to
      dispose of an easy recycling product, glutamate. Analysis of the expression of
      the gene revealed a close association with salt stress and Pro production. In
      young plantlets, free Pro content, Delta1-pyrroline-5-carboxylate synthase mRNA,
      delta-OAT activity, and delta-OAT mRNA were all increased by salt-stress
      treatment. These results suggest that for A. thaliana, the Orn pathway, together
      with the glutamate pathway, plays an important role in Pro accumulation during
      osmotic stress. Conversely, in 4-week-old A. thaliana plants, although free Pro
      level also increased under salt-stress conditions, the delta-OAT activity
      appeared to be unchanged and delta-OAT mRNA was not detectable. Delta1-pyrroline
      5-carboxylate synthase mRNA was still induced at a similar level. Therefore, for
      the adult plants the free Pro increase seemed to be due to the activity of the
      enzymes of the glutamate pathway.

PMID- 9576797
TI  - Dimethylsulfoniopropionate biosynthesis in Spartina alterniflora1. Evidence that
      S-methylmethionine and dimethylsulfoniopropylamine are intermediates.
AB  - The osmoprotectant 3-dimethylsulfoniopropionate (DMSP) occurs in Gramineae and
      Compositae, but its synthesis has been studied only in the latter. The DMSP
      synthesis pathway was therefore investigated in the salt marsh grass Spartina
      alterniflora Loisel. Leaf tissue metabolized supplied [35S]methionine (Met) to S
      methyl-l-Met (SMM), 3-dimethylsulfoniopropylamine (DMSP-amine), and DMSP. The 35S
      labeling kinetics of SMM and DMSP-amine indicated that they were intermediates
      and, consistent with this, the dimethylsulfonium moiety of SMM was shown by
      stable isotope labeling to be incorporated as a unit into DMSP. The identity of
      DMSP-amine, a novel natural product, was confirmed by both chemical and mass
      spectral methods. S. alterniflora readily converted supplied [35S]SMM to DMSP
      amine and DMSP, and also readily converted supplied [35S]DMSP-amine to DMSP;
      grasses that lack DMSP did neither. A small amount of label was detected in 3
      dimethylsulfoniopropionaldehyde (DMSP-ald) when [35S]SMM or [35S]DMSP-amine was
      given. These results are consistent with the operation of the pathway Met --> SMM
      --> DMSP-amine --> DMSP-ald --> DMSP, which differs from that found in Compositae
      by the presence of a free DMSP-amine intermediate. This dissimilarity suggests
      that DMSP synthesis evolved independently in Gramineae and Compositae.

PMID- 9576798
TI  - Drought-induced effects on nitrate reductase activity and mRNA and on the
      coordination of nitrogen and carbon metabolism in maize leaves 
AB  - Maize (Zea mays L.) plants were grown to the nine-leaf stage. Despite a
      saturating N supply, the youngest mature leaves (seventh position on the stem)
      contained little NO3- reserve. Droughted plants (deprived of nutrient solution)
      showed changes in foliar enzyme activities, mRNA accumulation, photosynthesis,
      and carbohydrate and amino acid contents. Total leaf water potential and CO2
      assimilation rates, measured 3 h into the photoperiod, decreased 3 d after the
      onset of drought. Starch, glucose, fructose, and amino acids, but not sucrose
      (Suc), accumulated in the leaves of droughted plants. Maximal extractable
      phosphoenolpyruvate carboxylase activities increased slightly during water
      deficit, whereas the sensitivity of this enzyme to the inhibitor malate
      decreased. Maximal extractable Suc phosphate synthase activities decreased as a
      result of water stress, and there was an increase in the sensitivity to the
      inhibitor orthophosphate. A correlation between maximal extractable foliar
      nitrate reductase (NR) activity and the rate of CO2 assimilation was observed.
      The NR activation state and maximal extractable NR activity declined rapidly in
      response to drought. Photosynthesis and NR activity recovered rapidly when
      nutrient solution was restored at this point. The decrease in maximal extractable
      NR activity was accompanied by a decrease in NR transcripts, whereas Suc
      phosphate synthase and phosphoenolpyruvate carboxylase mRNAs were much less
      affected. The coordination of N and C metabolism is retained during drought
      conditions via modulation of the activities of Suc phosphate synthase and NR
      commensurate with the prevailing rate of photosynthesis.

PMID- 9576799
TI  - Overexpression of nitrate reductase in tobacco delays drought-induced decreases
      in nitrate reductase activity and mRNA 
AB  - Transformed (cauliflower mosaic virus 35S promoter [35S]) tobacco (Nicotiana
      plumbaginifolia L.) plants constitutively expressing nitrate reductase (NR) and
      untransformed controls were subjected to drought for 5 d. Drought-induced changes
      in biomass accumulation and photosynthesis were comparable in both lines of
      plants. After 4 d of water deprivation, a large increase in the ratio of shoot
      dry weight to fresh weight was observed, together with a decrease in the rate of
      photosynthetic CO2 assimilation. Foliar sucrose increased in both lines during
      water stress, but hexoses increased only in leaves from untransformed controls.
      Foliar NO3- decreased rapidly in both lines and was halved within 2 d of the
      onset of water deprivation. Total foliar amino acids decreased in leaves of both
      lines following water deprivation. After 4 d of water deprivation no NR activity
      could be detected in leaves of untransformed plants, whereas about 50% of the
      original activity remained in the leaves of the 35S-NR transformants. NR mRNA was
      much more stable than NR activity. NR mRNA abundance increased in the leaves of
      the 35S-NR plants and remained constant in controls for the first 3 d of drought.
      On the 4th d, however, NR mRNA suddenly decreased in both lines. Rehydration at d
      3 caused rapid recovery (within 24 h) of 35S-NR transcripts, but no recovery was
      observed in the controls. The phosphorylation state of the protein was unchanged
      by long-term drought. There was a strong correlation between maximal extractable
      NR activity and ambient photosynthesis in both lines. We conclude that drought
      first causes increased NR protein turnover and then accelerates NR mRNA turnover.
      Constitutive NR expression temporarily delayed drought-induced losses in NR
      activity. 35S-NR expression may therefore allow more rapid recovery of N
      assimilation following short-term water deficit.

PMID- 9576800
TI  - In vitro reconstitution of electron transport from glucose-6-phosphate and NADPH
      to nitrite 
AB  - An NADPH-dependent NO2--reducing system was reconstituted in vitro using
      ferredoxin (Fd) NADP+ oxidoreductase (FNR), Fd, and nitrite reductase (NiR) from
      the green alga Chlamydomonas reinhardtii. NO2- reduction was dependent on all
      protein components and was operated under either aerobic or anaerobic conditions.
      NO2- reduction by this in vitro pathway was inhibited up to 63% by 1 mm NADP+.
      NADP+ did not affect either methyl viologen-NiR or Fd-NiR activity, indicating
      that inhibition was mediated through FNR. When NADPH was replaced with a glucose
      6-phosphate dehydrogenase (G6PDH)-dependent NADPH-generating system, rates of NO2
      reduction reached approximately 10 times that of the NADPH-dependent system.
      G6PDH could be replaced by either 6-phosphogluconate dehydrogenase or isocitrate
      dehydrogenase, indicating that G6PDH functioned to: (a) regenerate NADPH to
      support NO2- reduction and (b) consume NADP+, releasing FNR from NADP+
      inhibition. These results demonstrate the ability of FNR to facilitate the
      transfer of reducing power from NADPH to Fd in the direction opposite to that
      which occurs in photosynthesis. The rate of G6PDH-dependent NO2- reduction
      observed in vitro is capable of accounting for the observed rates of dark NO3-
      assimilation by C. reinhardtii.

PMID- 9576801
TI  - Adaptation of active proton pumping and plasmalemma ATPase activity of corn roots
      to low root medium pH 
AB  - Corn (Zea mays L.) root adaptation to pH 3.5 in comparison with pH 6. 0 (control)
      was investigated in long-term nutrient solution experiments. When pH was
      gradually reduced, comparable root growth was observed irrespective of whether
      the pH was 3.5 or 6.0. After low-pH adaptation, H+ release of corn roots in vivo
      at pH 5.6 was about 3 times higher than that of control. Plasmalemma of corn
      roots was isolated for investigation in vitro. At optimum assay pH, in comparison
      with control, the following increases of the various parameters were caused by
      low-pH treatment: (a) hydrolytic ATPase activity, (b) maximum initial velocity
      and Michaelis constant (c) activation energy of H+-ATPase, (d) H+-pumping
      activity, (e) H+ permeability of plasmalemma, and (f) pH gradient across the
      membranes of plasmalemma vesicles. In addition, vanadate sensitivity remained
      unchanged. It is concluded that plasmalemma H+-ATPase contributes significantly
      to the adaptation of corn roots to low pH. A restricted net H+ release at low pH
      in vivo may be attributed to the steeper pH gradient and enhanced H+ permeability
      of plasmalemma but not to deactivation of H+-ATPase. Possible mechanisms
      responsible for adaptation of plasmalemma H+-ATPase to low solution pH during
      plant cultivation are discussed.

PMID- 9576802
TI  - Purification and characterization of phosphoribulokinase from the marine
      chromophytic alga Heterosigma carterae.
AB  - In this study we characterized phosphoribulokinase (PRK, EC 2.7.1. 19) from the
      eukaryotic marine chromophyte Heterosigma carterae. Serial column chromatography
      resulted in approximately 300-fold purification of the enzyme. A polypeptide of
      53 kD was identified as PRK by sequencing the amino terminus of the protein. This
      protein represents one of the largest composite monomers identified to date for
      any PRK. The native holoenzyme demonstrated by flow performance liquid
      chromatography a molecular mass of 214 +/- 12.6 kD, suggesting a tetrameric
      structure for this catalyst. Because H. carterae PRK activity was insensitive to
      NADH but was stimulated by dithiothreitol, it appears that the enzyme may require
      a thioredoxin/ferredoxin rather than a metabolite mode of regulation. Kinetic
      analysis of this enzyme demonstrated Michaelis constant values of ribulose-5
      phosphate (226 microM) and ATP (208 microM), respectively. In summary, H.
      carterae PRK is unique with respect to holoenzyme structure and function, and
      thus may represent an alternative evolutionary pathway in Calvin-cycle kinase
      development.

PMID- 9576803
TI  - Cascade liposomal triggering: light-induced Ca2+ release from diplasmenylcholine
      liposomes triggers PLA2-catalyzed hydrolysis and contents leakage from DPPC
      liposomes.
AB  - We have previously reported a direct triggering approach [Thompson, D. H., et al.
      (1996) Biochim. Biophys. Acta 1279, 25-34; Gerasimov, O. V., et al. (1997)
      Biochim. Biophys. Acta 1324, 200-214] based on the facile degradation of
      plasmenylcholine and diplasmenylcholine vinyl ether linkages by either
      photooxidation or low-pH environments. This report describes a novel, cascade
      type triggering technique that utilizes liposome photooxidation and contents
      release to activate an enzyme capable of destabilizing conventional
      phosphatidylcholine liposomes. Our application of this concept employs a mixture
      of two different liposome populations, one composed of synthetic
      diplasmenylcholine (1, 2-dihexadec-1'-enyl-sn-glycero-3-phosphocholine, DPPlsCho)
      containing Ca2+ as a signaling agent for phospholipase A2 (PLA2) and the second
      composed of 1, 2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC) with
      encapsulated calcein as the reporter molecule. Bacteriochlorophyll (BChl)
      sensitized photorelease of Ca2+ from PLA2-resistant DPPlsCho liposomes activates
      extravesicular PLA2, thereby promoting catalyzed DPPC hydrolysis in a secondary
      triggering reaction, leading to calcein release. BChl/DPPlsCho/DHC/DPPE
      PEG5000/Ca2+IN (0.5:85:10:5) liposomes can be phototriggered using 800 nm
      excitation, resulting in Ca2+ release (t50% release = 15 min) that cocatalyzes
      the release of calcein (t50% release = 40 min) from DPPC liposomes (1.5 mM total
      lipid in DPPlsCho liposomes, 0.18 mM DPPC, 210 micro M final Ca2+ concentration,
      90 units of PLA2/ml, 50 mM calcein, and 36 micro M EDTA). No appreciable calcein
      release occurs in the absence of either PLA2 or BChl/DPPlsCho/DHC/DPPE
      PEG5000/CaIN liposomes. The implications of this cascade triggering technique on
      drug delivery approaches are briefly discussed.

PMID- 9576804
TI  - Application of cystamine and N,N'-Bis(glycyl)cystamine as linkers in
      polysaccharide-protein conjugation.
AB  - Pneumococcal polysaccharide type 6B, 14, or 23F (35-70 kDa) was activated with
      cyanogen bromide and modified with cystamine. After reduction of the spacer, the
      thiol-containing (i.e. cysteamine-modified) polysaccharide obtained was added in
      a 5-10-fold molar excess to bromoacetylated tetanus toxoid to give thioether
      linked polysaccharide-protein conjugates in a yield of 10-20%. This approach
      failed for preparing a type 19F polysaccharide-protein conjugate, possibly due to
      intramolecular elimination of cysteamine from the reduced 19F polysaccharide.
      When N,N'-bis(glycyl)cystamine was introduced as a spacer molecule, the
      elimination of the reduced spacer was suppressed, thus allowing preparation of a
      19F polysaccharide-tetanus toxoid conjugate (15%).

PMID- 9576805
TI  - Detection of oligonucleotide hybridization on a single microparticle by time
      resolved fluorometry: quantitation and optimization of a sandwich type assay.
AB  - Uniformly sized (50 micro m) porous glycidyl methacrylate/ethylene dimethacrylate
      particles (SINTEF) were used as the solid phase in a sandwich type mixed-phase
      hybridization assay based on time-resolved fluorescence detection on a single
      particle. These particles were coated with oligodeoxyribonucleotide probes by
      conventional phosphoramidite chain assembly. An oligodeoxyribonucleotide bearing
      a photoluminescent europium(III) chelate, ?2,2',2",2"'-??4'-?4"'-[(4, 6-dichloro
      1,3,5-triazin-2-yl)amino]phenyl?-2,2':6',2"-terpyrid ine-6, 6"
      diyl?bis(methylenenitrilo)?tetrakis(acetato)?eur opi um(III), was hybridized to a
      complementary sequence of the target oligonucleotide, and the resulting duplex
      was further hybridized to the particle-bound probes. The latter binding was
      quantified by time-resolved measurement of the emission signal of a single
      particle. Kinetics of hybridization and the effect of the concentration of the
      target oligomer and the fluorescently tagged probe on the efficiency of
      hybridization were studied. The intensity of the emission signal was linearly
      related to the concentration of the target oligomer over a range of 5 orders of
      magnitude. The length of the complementary region between the target oligomer and
      the particle-bound probe was varied, and the effect of point mutations and
      deletions on the hybridization efficiency was determined in each case. The
      maximal selectivity was observed with 10-16-base pair complementary sequences,
      the optimal length depending on the oligonucleotide loading on the particle.
      Discrimination between the complete matches and point mismatches was unequivocal,
      a single point mutation and/or deletion decreasing the efficiency of
      hybridization by more than 2 orders of magnitude.

PMID- 9576807
TI  - Solution structure of a DNA complex with the fluorescent bis-intercalator TOTO
      modified on the benzothiazole ring.
AB  - We have used two-dimensional 1H NMR spectroscopy to determine the solution
      structure of the DNA oligonucleotide d(5'-CGCTAGCG-3')2 complexed with the bis
      intercalating dye 1,1'-(4,4,8,8-tetramethyl-4, 8-diazaundecamethylene)bis-4-[3
      ethyl-2,3-dihydro(benzo-1, 3-thiazolyl)-2-methylidene]quinolinium tetraiodide
      (TOTOEt). The determination of the structure was based on a total relaxation
      matrix analysis of the NOESY cross-peak intensities. DQF-COSY spectra were used
      to obtain coupling constants for the deoxyribose ring protons. The coupling
      constants were transformed into angle estimates. The NOE-derived distance and
      dihedral restraints were applied in restrained molecular dynamics calculations.
      Twenty final structures each were generated for the TOTOEt complex from both A
      form and B-form double-stranded (ds) DNA starting structures, giving a total of
      40 final structures. Since many NOE contacts were observed between TOTOEt and
      dsDNA, the resulting structure has a fairly high resolution and allows
      determination of local features in the dsDNA structure after TOTOEt binding. The
      root-mean-square (rms) deviation of the coordinates for the 40 structures of the
      complex was 0.52 A. The local DNA structure is distorted in the complex. The
      helix is unwound by 80 degrees and has an overall helical repeat of 12 base
      pairs, caused by bis-intercalation of TOTOEt. The benzothiazole ring system is
      twisted relative to the quinoline in the uncomplexed TOTOEt molecule. The site
      selectivity of TOTOEt for the CTAG.CTAG site is explained by its ability to adapt
      to the base pair propeller twist of dsDNA to optimize stacking and the
      hydrophobic interaction between the thymidine methyl group and the benzothiazole
      ring. The polypropylene amine linker chain is located in the minor groove of
      dsDNA. The N-ethyl group on the benzothiazole of TOTOEt is placed in the major
      groove pointing toward the center of the oligonucleotide and the dyad symmetry
      axis of the complex. This orientation seems to make it feasible to create a TOTO
      analogue with a linker connecting the two chromophores in the major groove. The
      design of such an analogue and a macrocyclic analogue with a linker in both the
      major groove and the minor groove seems to be straightforward.

PMID- 9576806
TI  - Streptavidin in antibody pretargeting. 2. Evaluation Of methods for decreasing
      localization of streptavidin to kidney while retaining its tumor binding
      capacity.
AB  - An investigation has been conducted to determine if the kidney localization of
      recombinant streptavidin can be decreased to improve its characteristics in
      pretargeting protocols. Three different methods of accomplishing this were
      evaluated. The first method, blocking kidney uptake with a preadministration of
      recombinant streptavidin in which biotin occupied all of the binding sites, was
      unsuccessful. In a second method, l-lysine administration was used to block
      kidney localization. This method worked well, decreasing the concentration to 29%
      of the unmodified amount at 8 h postinjection. However, this method suffered from
      a requirement for constant infusion of lysine during the period of observation. A
      third method, use of succinylated recombinant streptavidin, was found to be the
      best approach. Succinylation of streptavidin was readily accomplished with very
      good protein recovery. With the succinylated streptavidin, the kidney
      concentration was only 14% of that of nonmodified streptavidin at 4 h
      postinjection. While these results demonstrated that the concentration of
      streptavidin could be decreased in the kidney, it was important to assess whether
      the tumor colocalization of streptavidin with biotinylated antibody was affected
      under those conditions. As part of our continuing investigation of pretargeting,
      a new water-solubilized biotinidase-stabilized biotinylation reagent was
      prepared. Using that reagent in a pretargeting experiment, an equivalent quantity
      of succinylated recombinant streptavidin as biotinylated antibody Fab' was
      localized in a tumor xenograft model. In that experiment, the kidney
      concentration was decreased to less than 10% of that obtained with unmodified
      recombinant streptavidin at 24 h postinjection. The results of our investigation
      have demonstrated that succinylation of streptavidin improves its distribution
      characteristics for pretargeting applications. The fact that succinylated
      streptavidin has no specific tissue localization should allow its use as a
      carrier of radioactivity in "two-step" pretargeting protocols.

PMID- 9576808
TI  - Preparation of conjugates of oligodeoxynucleotides and lipid structures and their
      interaction with low-density lipoprotein.
AB  - The high expression level of receptors for low-density lipoprotein (LDL) on tumor
      cells makes LDL an attractive carrier for selective delivery of drugs to these
      cells. The aim of this study is to allow incorporation of oncogene-directed
      antisense oligodeoxynucleotides (ODNs) into the lipid moiety of LDL. Therefore,
      ODNs were conjugated with oleic acid, cholesterol, and several other steroid
      lipids. These latter steroid lipids were synthesized starting from bile acids and
      were varied in lipophilicity by attaching oleic acid ester structures. The lipid
      structures, activated as pentafluorophenyl esters, were conjugated in solution
      phase to 3'-amino-tailed ODNs. The ODNs conjugated with lithocholic acid, oleic
      acid, and cholesterol could easily be purified by reversed phase (RP)-HPLC.
      However, the ODNs conjugated with the oleoyl steroid ester structures
      irreversibly bound to the column material. These highly lipidic ODNs were
      separated from the nonconjugated ODN by electrophoresis in a 1% low-melting
      agarose gel containing 0.1% Tween 20. This method was found to be very effective
      in isolating the ODNs conjugated to the oleoyl steroid ester structures. The ODNs
      conjugated with cholesterol and the oleoyl esters of lithocholic and cholenic
      acid associated readily and nearly completely with LDL. However, the less lipidic
      ODNs and the ODN conjugated with the dioleoyl ester of chenodeoxycholic acid did
      not and did incompletely associate, respectively. Lithocholic acid and oleic acid
      are probably not sufficiently lipophilic to induce association with LDL, whereas
      the dioleoyl ester structure is probably too bulky and extended to allow
      partitioning into the lipid moiety of LDL. We conclude that several of the lipid
      ODNs can associate readily with LDL, enabling delivery of oncogene-directed
      antisense ODNs via the LDL receptor pathway.

PMID- 9576809
TI  - Terbium chelate membrane label for time-resolved, total internal reflection
      fluorescence microscopy of substrate-adherent cells.
AB  - A chelating agent conjugated to a lipid was synthesized by reacting the
      dianhydride form of diethylenetriaminepentaacetic acid sequentially with 4
      aminosalicylate and dioleoylphosphatidylethanolamine. The product, DOPE-YAS-Tb,
      exhibits photophysical properties characteristic of a chelated Tb3+ ion bound to
      an organic triplet donor: an excitation maximum at 310 nm, narrow emission bands
      at 490, 545, 590, and 625 nm, and a lifetime of 1.57 ms. The suitability of DOPE
      YAS-Tb as a membrane-staining agent for morphological studies of cultured cells
      using total internal reflection fluorescence microscopy (TIRFM) was investigated.
      Swiss albino mouse 3T3 cells were cultured on silica and polystyrene substrates.
      Time-resolved detection was employed to reject short-lived background emission
      (autoemission from the cells and/or the polymer substrate), which allowed the
      long-lived Tb3+ emission to be selectively imaged. The results show that time
      resolved TIRFM of cells stained with DOPE-YAS-Tb is an effective method of
      quantitatively examining the cell morphology in situations where background due
      to autoemission from cells and/or the substrate material is problematic.

PMID- 9576810
TI  - A series of 6-(omega-methanesulfonylthioalkoxy)-2-N-methyl- 1,2,3, 4
      tetrahydroisoquinolines: cysteine-reactive molecular yardsticks for probing
      alpha2-adrenergic receptors.
AB  - A series of 6-(omega-methanesulfonylthioalkoxy)-2-N-methyl-1,2,3, 4
      tetrahydroisoquinolines (7a-d) was prepared and characterized as SH-reactive
      molecular yardsticks useful in probing alpha2-adrenergic receptors. Rapid
      displacement of the methanesulfonyl group by a cysteine residue in dilute aqueous
      solution with concomitant formation of a disulfide conjugate was verified by
      MALDI-TOF mass spectrometric analysis of the reaction of 7a with a cysteine
      containing decapeptide. 7a-d all showed a marked affinity for the three different
      variants of human alpha2-adrenergic receptors: H alpha(2A)wt, H alpha(2B)wt, and
      mutant H alpha(2A)Ser201Cys197. However, only the mutated receptor (H
      alpha(2A)Ser201Cys197) was irreversibly inactivated, and the extent of
      inactivation in this case was linearly dependent on the length of the side chain
      of 7a-d. These results show that the molecular yardstick approach tested here can
      provide useful information for modeling receptor proteins.

PMID- 9576811
TI  - Disulfide-tethered solid supports for synthesis of photoluminescent
      oligonucleotide conjugates: hydrolytic stability and labeling on the support.
AB  - Several new disulfide-tethered solid supports (S1-S5) were synthesized, and their
      resistance against ammonolysis was tested. Among these supports, only the one
      bearing an N-[15-[(4, 4'-dimethoxytrityl)oxy]-12,13-dithiapentadecanoyl] linker
      (S4b) tolerated ammonolysis and exhibited properties compatible with the
      oligonucleotide synthesis by phosphoramidite strategy. The applicability of this
      disulfide linker structure in postsynthetic oligonucleotide labeling on the
      support was demonstrated by introduction of two photoluminescent lanthanide
      chelates or two dansyl groups to the N4-(6-aminohexyl) amino-modified cytosine
      residues at the 5' end of the oligonucleotide sequence. Subsequent release of the
      resulting conjugates as their 3'-phosphates was achieved by reductive cleavage of
      the disulfide bond and precipitation of the conjugate from the solution with
      ethanol. The fluorescently tagged oligomer obtained showed hybridization
      properties similar to those of oligonucleotides labeled in solution.

PMID- 9576812
TI  - Role of cross-linking agents in determining the biochemical and pharmacokinetic
      properties of Mgr6-clavin immunotoxins.
AB  - Several immunotoxins (ITs) were synthesized by the attachment of clavin, a
      recombinant toxic protein derived from Aspergillus clavatus, to the monoclonal
      antibody Mgr6 that recognizes an epitope of the gp185(HER-2) extracellular domain
      expressed on breast and ovarian carcinoma cells. Conjugation and purification
      parameters were analyzed in an effort to optimize the antitumor activity and
      stability of the ITs in vivo. To modulate the in vitro and in vivo properties of
      the immunotoxins, different coupling procedures were used and both disulfide and
      thioether linkages were obtained. Unhindered and hindered disulfide with a methyl
      group linkage ethyl S-acetyl 3-mercaptopropionthioimidate ester hydrochloride
      (AMPT) or ethyl S-acetyl 3-mercaptobutyrothioimidate ester hydrochloride (M-AMPT)
      were obtained by reaction with recombinant clavin, while the monoclonal antibody
      Mgr6 was derivatized with ethyl 3-[(4-carboxamidophenyl)dithio]propionthioimidate
      ester hydrochloride (CDPT). To achieve higher hindrance (a disulfide bond with a
      geminal dimethyl group), Mgr6 was derivatized with the N-hydroxysuccinimidyl 3
      methyl-3-(acetylthio)butanoate (SAMBA) and clavin with CDPT. To evaluate the
      relevance of the disulfide bond in the potency and pharmacokinetic behavior of
      the ITs, a conjugate consisting of a stable thioether bond was also prepared by
      derivatizing Mgr6 with the N-hydroxysuccinimidyl ester of iodoacetic acid (SIA)
      and clavin with AMPT. The immunotoxins were purified and characterized using a
      single-step chromatographic procedure. Specificity and cytotoxicity were assayed
      on target and unrelated cell lines. The data indicate that the introduction of a
      hindered disulfide linkage into ITs has little or no effect on antitumor activity
      and suggest that disulfide cleavage is essential for activity; indeed, the
      intracellularly unbreakable thioether linkage produced an inactive IT. Analysis
      of IT stability in vitro showed that the release of mAb by incubation with
      glutathione is proportional to the presence of methyl groups and increases
      exponentially with the increase in steric hindrance. Analysis of the
      pharmacokinetic behavior of ITs in Balb/c mice given intravenous bolus injections
      indicated that ITs with higher in vitro stability were eliminated more slowly;
      i.e., the disulfide bearing a methyl group doubled the beta-phase half-life (from
      3.5 to 7.1 h) compared with that of the unhindered, while a geminal dimethyl
      protection increased the elimination phase to 24 h. The thioether linkage showed
      its intrinsic stability with a beta-phase half-life of 46 h. The thioether
      linkage also increased the distribution phase from 17 to 32 min. The in vitro
      characteristics and in vivo stability of Mgr6-clavin conjugates composed of a
      methyl and dimethyl steric hindered disulfide suggest clinical usefulness.

PMID- 9576813
TI  - Temperature-dependent associating property of liposomes modified with a
      thermosensitive polymer.
AB  - Novel temperature-sensitive liposomes having surface properties that can be
      controlled by temperature were designed as liposomes coated with poly(N
      isopropylacrylamide), which exhibits a hydrated coil to dehydrated globule
      transition at ca. 32 degrees C. To obtain the polymer with anchoring groups to
      the liposome, a copolymer of N-isopropylacrylamide and octadecyl acrylate (99:1,
      mol/mol) was synthesized by radical copolymerization. The copolymer revealed the
      transition near 30 degrees C. Liposomes made from various phospholipids were
      prepared by sonication and coated with the copolymer. When
      dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine were used as
      liposome lipids, remarkable aggregation and fusion of the copolymer-modified
      liposomes took place between the transition temperature of the copolymer and the
      gel-liquid-crystalline transition temperature (Tc) of the lipid membranes.
      However, above the Tc, association between the liposomes was much less
      significant, although the copolymer is still hydrophobic. In the case of the
      copolymer-modified dilauroylphosphatidylcholine liposome, the membrane of which
      takes on a liquid-crystalline state under the experimental conditions,
      association between the liposomes also hardly occurred even when the copolymer
      became hydrophobic. On the other hand, below the transition temperature of the
      copolymer, the copolymer-modified liposomes were very stable and aggregation of
      the liposomes was not observed, irrespective of membrane lipid. Results obtained
      in this study demonstrate that the copolymer chains fixed on the surface of the
      liposome with a solid membrane promote aggregation and fusion of the liposomes by
      hydrophobic interactions between the copolymer chains and/or between the
      copolymer chains and the liposome membranes above the transition temperature of
      the copolymer.

PMID- 9576814
TI  - Alkaline phosphatase activatable polymeric cross-linkers and their use in the
      stabilization of proteins.
AB  - We report the synthesis of polymeric cross-linking agents, poly(glutamic acid)
      poly(phosphorothioates), and their use in the cross-linking and stabilization of
      proteins upon treatment with alkaline phosphatase. We have shown that
      poly(phosphorothioates) are excellent substrates of alkaline phosphatase,
      yielding thiolated polymers which react covalently with electrophilic groups
      introduced into the proteins. Three proteins of different structure and function
      were cross-linked using this method: calf intestinal alkaline phosphatase,
      glucose oxidase (Aspergillus niger), and (R)-phycoerythrin. The cross-linking of
      alkaline phosphatase is self-catalyzed since this enzyme catalyzes the hydrolysis
      of phosphates, unmasking thiolates which react with the maleimide prederivatized
      alkaline phosphatase. Incubation of buffered solutions of native alkaline
      phosphatase at 45 degreesC for 7-14 days resulted in a 35% higher loss of
      enzymatic activity compared to that of cross-linked enzyme. The effect of cross
      linking glucose oxidase is even more notable, ranging from 800% stabilization at
      37 degrees C and pH 9.0 to 3000% at 37 degrees C and pH 7.4. (R)-Phycoerythrin
      cross-linked with 1-3 equiv of poly(phosphorothioates) and incubated at 45
      degrees C for 45 days was 20% more fluorescent than the native (R)-phycoerythrin
      subjected to the same conditions. The stabilizing effect of cross-linking was
      confirmed by comparing the rate of loss of quaternary structure of the cross
      linked (R)-phycoerythrin with that of the native protein.

PMID- 9576816
TI  - Synthesis of 6beta-[(2'-Aminoethyl)carboxamidomethyl]estradiol and preparation of
      estradiol probes.
AB  - Reformatsky reaction of 3, 17beta-bis[(2-trimethylsilyl)ethoxymethyl]-1,3, 5(10)
      estratrien-6-one (2) with bromoethyl acetate and zinc gave the ester (3) in 60%
      yield which upon treatment with methanesulfonyl chloride in pyridine afforded the
      olefinic esters (4 and 5) as an endo and exo mixture (67:33 ratio) in 81% yield.
      Hydrolysis of the SEM protective groups in compounds 4 and 5 followed by
      hydrogenation of the resulting hydroxy compounds 6 and 7 using 10% Pd/C afforded
      an epimeric mixture (beta:alpha = 79:21) of 6-[(ethoxycarbonyl)methyl]estradiol
      (8a and 8b) in 95% yield. Hydrolysis of the ethyl esters (8a and 8b) using sodium
      hydroxide gave the acid (9a and 9b) in 81% yield. The epimeric mixture of acids
      (9a and 9b) was activated, treated with tert-butyl-N-(2-aminoethyl)carbamate
      (10), and purified by HPLC to afford 6beta-[[[(2-tert
      butoxycarbonyl)amino]ethyl]carboxamidomethyl] estradiol (11) in 39% yield as the
      major isomer. Hydrolysis of the BOC group in compound 11 using TFA afforded the
      desired 6beta-[(2-aminoethyl)carboxamidomethyl]estradiol 12 in 50% yield. The
      biotinylated estradiol probe 14, fluorescent probe 16, and chemiluminescent probe
      18 were prepared from 6beta-[(2'-aminoethyl)carboxamidomethyl]estradiol (12) and
      the corresponding biotin, 5-carboxyfluorescein, and 10-(3-sulfopropyl)-N-tosyl-N
      (3-carboxypropyl)acridinium-9-carboxamide N-succinimidyl esters (13, 15, and 17)
      in 65-74% yield and 99% purity.

PMID- 9576815
TI  - Thermally stabilized immunoconjugates: conjugation of antibodies to alkaline
      phosphatase stabilized with polymeric cross-linkers.
AB  - A method of conjugating poly(glutamic acid) poly(phosphorothioate)-cross-linked
      alkaline phosphatase to maleimide-derivatized immunoglobulin is described.
      Intramolecular autocatalyzed cross-linking of alkaline phosphatase at 2:1 to 4:1
      polymer:enzyme ratios introduced 32-68 thiolates on the surface of the enzyme.
      Depending on the stoichiometry of polymer to enzyme, the cross-linked alkaline
      phosphatase retained 75-90% of its native catalytic activity. The cross-linked
      thiolate-functionalized alkaline phosphatase was conjugated to maleimide
      derivatized immunoglobulin. Compared to a control prepared using non-cross-linked
      alkaline phosphatase, these conjugates were smaller in size and more stable to
      heat. The enzymatic activity of the cross-linked conjugates after incubation at
      45 degrees C and pH 7.5 for 25 days was 35% higher than those of the highest
      activity control conjugates. The conjugation process could be controlled by
      varying the stoichiometries of poly(glutamic acid) poly(phosphorothioate),
      alkaline phosphatase, and immunoglobulin.

PMID- 9576818
TI  - Synthesis of new d-propoxyphene derivatives and the development of a
      microparticle-based immunoassay for the detection of propoxyphene and
      norpropoxyphene 

PMID- 9576817
TI  - Photostable chlorophyll a conjugated with poly(vinylpyrrolidone)-smectite
      catalyzes photoreduction and hydrogen gas evolution by visible light.
AB  - Chlorophyll a was adsorbed to a synthetic smectite intercalated by
      poly(vinylpyrrolidone) (PVP) to form the chlorophyll-PVP-smectite conjugate (Chl
      PVP-SME) having an absorption maximum at 677 nm. The conjugate was found to be
      stable toward light illumination in comparison with chlorophyll-smectite,
      chlorophyll-PVP, and free chlorophyll a. Chl-PVP-SME had a photoinduced activity
      for catalyzing the reduction of methyl viologen. Furthermore, the evolution of
      hydrogen gas was observed when an aqueous suspension containing Chl-PVP-SME,
      methyl viologen (an electron carrier), 2-mercaptoethanol (an electron donor), and
      hydrogenase was illuminated by visible light.

PMID- 9576819
TI  - Levels of sentence constraint and lexical decision in the two hemispheres.
AB  - This study used a lexical decision-priming paradigm to investigate the relative
      sensitivity of the two cerebral hemispheres to linguistic constraint. Level of
      constraint of syntactically and semantically correct priming sentences was
      determined by the Cloze procedure and constraint was manipulated by means of
      these sentences. High-, medium-, and low-constraining as well as neutral
      incomplete sentences were presented centrally prior to the appearance of a target
      word or nonword either to the left or to the right visual field of sixteen
      righthanded subjects. The hypothesis tested was that the left hemisphere benefits
      more from linguistic constraint than the right hemisphere. Although reaction time
      data generally supported this hypothesis, the right hemisphere also seemed to
      benefit from the constraint produced by high-constraint sentences. The relevance
      of these findings to the manner in which the two hemispheres process different
      kinds of linguistic material is discussed.

PMID- 9576820
TI  - Event-related brain potentials elicited during phonological processing
      differentiate subgroups of reading disabled adolescents.
AB  - Visual and auditory rhyme judgment tasks were administered to adolescent
      dyslexics and normal readers while event-related brain potentials were recorded.
      Reading disabled subjects were split into two groups based on a median split of
      scores on a visual non-word decoding test. The better decoders were called
      Phonetics and the poorer decoders were referred to as Dysphonetics. Single
      syllable, real word stimuli were used, and both rhyming and non-rhyming targets
      had a 50% chance for matching orthography. In the visual paradigm the normal
      readers exhibited a left frontal CNV before targets, a large reduction in frontal
      N400 for matching orthography (orthographic priming), and a large reduction in
      parietal N400 for rhyming targets (phonological priming). Dysphonetics had an
      intact CNV and orthographic priming, but the group's phonological priming was
      very reduced. Phonetics showed both orthographic and phonological priming but had
      a marked reduction in their CNV. In the auditory task, controls showed a left
      parietal N400 priming effect for rhyming targets. Dysphonetics showed a similar
      bilateral effect. The Phonetics did not show a normal priming effect, but
      produced evidence for priming at a longer latency. Additionally, the Phonetic
      group responded more slowly than either of the other two groups, who responded
      with similar latencies. These results support the separation of the reading
      disabled into a group that has difficulty translating orthography into phonology,
      and a group that is slower functioning and has reduced capacity in preparing for
      a response.

PMID- 9576821
TI  - Sentence comprehension in Alzheimer's disease.
AB  - We asked 22 patients with Alzheimer's disease (AD) to respond to simple probes of
      sentences where we manipulated grammatical factors, semantic factors, and
      cognitive resource demands associated with a sentence. The results demonstrated
      limitations in the cognitive resources needed to appreciate atypical syntactic
      thematic mapping relations and difficulty processing selection restrictions
      associated with a verb. By comparison, comprehension in AD was not influenced by
      the active or passive voice of a sentence. These findings are consistent with the
      hypothesis that impaired sentence comprehension in AD is multifactorial in
      nature, including difficulty processing cognitive resource and semantic aspects
      of sentences.

PMID- 9576822
TI  - Knowledge inhibition and N400: a study with words that look like common words.
AB  - In addition to their own representations, low frequency words, such as BRIBE, can
      covertly activate the representations of higher frequency words they look like
      (e.g., BRIDE). Hence, look-alike words can activate knowledge that is
      incompatible with the knowledge corresponding to accurate representations.
      Comparatively, eccentric words, that is, low frequency words that do not look as
      much like higher frequency words, are less likely to activate incompatible
      knowledge. This study focuses on the hypothesis that the N400 component of the
      event-related potential reflects the inhibition of incompatible knowledge. This
      hypothesis predicts that look-alike words elicit N400s of greater amplitudes than
      eccentric words in conditions where incompatible knowledge is inhibited. Results
      from a single item lexical decision experiment are reported which support the
      inhibition hypothesis.

PMID- 9576823
TI  - Syntactic facilitation in agrammatic sentence production.
AB  - Recently, proposals have been made to relate processing difficulties in aphasic
      language performance to limitations in resources for grammatical processing
      (Carpenter et al., 1994; Hagiwara, 1995; Kolk, 1995; Martin & Romani, 1994). Such
      proposals may account for a defining characteristic of agrammatic sentence
      production: reduced syntactic complexity. Syntactic structures that require deep
      hierarchical processing or reversals of canonical word order make demands
      exceeding limited resources. In the present study, we investigate the possibility
      of counteracting hypothesized resource limitations by increasing the availability
      of relatively complex sentences (i.e., datives and passives). The phenomenon of
      "syntactic priming" has been observed in a number of studies with healthy adults
      (e.g., Bock, 1986). With respect to Broca's aphasia, we hypothesized that
      increased availability of a syntactic structure, due to syntactic priming,
      results in a lesser demand on (limited) resources for sentence production. We
      elicited speech from 12 Broca's aphasics and 12 control subjects in three
      different conditions: spontaneous speech, picture description without priming,
      and picture description with priming. In addition, we varied instructions, in
      order to determine the role of strategies. The main findings were that (a) Brocas
      show stronger syntactic priming effects than controls; (b) the effects are
      automatic rather than strategic; and (c) in conditions with priming, Brocas
      produce relatively complex sentences (e.g., passives). We discuss these results
      in relation to capacity theories.

PMID- 9576824
TI  - Semantic influences on thematic role assignment: evidence from normals and
      aphasics.
AB  - We report two studies that examine the role of semantic influences in the
      assignment of thematic roles. Semantic factors were manipulated by contrasting
      sentences in which one noun argument was a plausible filler of only one thematic
      role (e.g., the painting in The artist disliked the painting) with sentences in
      which both noun arguments were plausible fillers of both thematic roles (e.g.,
      The robin ate the insect). Subjects were required to make plausibility judgments
      to sentences presented auditorily. Experiment 1 examined RTs of normal subjects
      on the plausibility judgment task. In Experiment 2, the same sentences were
      presented to aphasic patients identified as "asyntactic" comprehenders. In
      Experiment 1, RTs were speeded by semantic constraints on thematic assignment,
      particularly when the role-constrained NP occurred early in the sentence (as in
      The painting was disliked by the artist). The aphasic performance patterns in
      Experiment 2 paralleled those of normal subjects, but in greatly exaggerated
      fashion. The patients exhibited high error rates on sentences where semantic
      constraints conflicted with the syntactically based assignments, even on
      sentences with canonical (S-V-O) word order (e.g., #The deer shot the hunter).

PMID- 9576825
TI  - Different neural circuits subserve reading before and after therapy for acquired
      dyslexia.
AB  - Rehabilitative measures for stroke are not generally based on basic
      neurobiological principles, despite evidence from animal models that certain
      anatomical and pharmacological changes correlate with recovery. In this report,
      we use functional magnetic resonance imaging (fMRI) to study in vivo human brain
      reorganization in a right handed patient with an acquired reading disorder from
      stroke. With phonological dyslexia, her whole-word (lexical) reading approach
      included inability to read nonwords and poor reading of function words. Following
      therapy, she was able to read nonwords and function words, and preferred a
      decompositional (sub-lexical) strategy in general. fMRI was performed during a
      reading task before and after treatment. Prior to therapy, her main focus of
      brain activation was in the left angular gyrus (area 39). After therapy, it was
      instead in the left lingual gyrus (area 18). This result suggests first that it
      is possible to alter brain physiology with therapy for acquired language
      disorders, and second, that two reading strategies commonly used in normal
      reading use distinct neural circuits, possibly reconciling several conflicting
      neuroimaging studies of reading.

PMID- 9576827
TI  - Cardiac neural crest cells provide new insight into septation of the cardiac
      outflow tract: aortic sac to ventricular septal closure.
AB  - A great deal is unclear about the process of cardiac outflow septation. Much
      controversy exists regarding the precise details of tissue origins and movements
      of various components. The contribution of the cardiac neural crest to
      aorticopulmonary and distal truncal septation has been described; however, the
      distribution of the neural crest in the proximal outflow and heart is unknown.
      The present study describes the movement of cardiac neural crest cells from the
      caudal pharyngeal arches into the outflow tract and base of the heart during the
      period of outflow septation. Using quail-chick chimeras we found that the cardiac
      neural crest was distributed to all levels of the outflow tract and into the base
      of the heart. Septation of the outflow tract lumen occurred by two different
      processes that involved the cardiac neural crest directly. Cardiac neural crest
      cells were also distributed to regions of the outflow tract that correlated with
      sites of remodeling, such as the aortic sac as it was remodeled into the base of
      the ascending aorta and pulmonary trunk, the distal truncus that was patterned
      into the two semilunar valves and in the proximal conotruncus where
      muscularization of the ridges and septum occurred. Additionally, cardiac neural
      crest cells were found at the site of closure of the ventricular septum, in the
      wall of the pulmonary infundibulum, and transiently in the wall of the aortic
      vestibule. Contrary to current thinking, not all of the condensed mesenchyme in
      the outflow tract during septation was derived from neural crest.

PMID- 9576828
TI  - Spontaneous transdifferentiation of quail pigmented epithelial cell is
      accompanied by a mutation in the Mitf gene.
AB  - An ectopic neural retina is formed at the outer layer of the retina in the silver
      homozygote (B/B) of the Japanese quail. In situ hybridization and
      immunohistochemical analysis revealed that cells in the outer layer of retina
      first expressed a pigment-cell-specific gene, mmp115, and then began to express a
      neural marker in B/B embryos, indicating that the ectopic neural retina is formed
      via transdifferentiation of differentiated pigmented epithelial cells (PECs). An
      in vitro study revealed that cultured retinal PECs (rPECs) from B/B embryos
      exhibit less pigment granule and a higher growth rate than cells from
      heterozygotes (B/+). B/+ PECs stopped proliferating when confluency was reached,
      while B/B PECs continued to proliferate. Some B/B cells overlaid other B/B cells
      and formed lentoid bodies. Immunological analysis revealed that B/B rPECs
      transdifferentiated to lens cells and neural cells in vitro with no addition of
      basic FGF (bFGF), while B/+ rPECs required bFGF to transdifferentiate. Expression
      of PEC-specific genes, mmp115, tyrosinase, and TRP-1, was downregulated, but that
      of Mitf and pax6 was upregulated in B/B PECs. Antibody against Mitf stained the
      nucleus of B/+ PECs but not that of B/B cells, suggesting that the normal Mitf is
      not present in the silver homozygote due to mutation. Sequence analysis revealed
      that Mitf from the silver homozygote has an amino acid substitution in the basic
      region and is truncated in the C-terminal region. Transient transfection analysis
      revealed that Mitf from the silver homozygote exhibits a lower level of activity
      than wild-type Mitf with respect to transactivation of the mmp115 promoter.
      Furthermore, overexpression of chicken Mitf induced normal pigmentation in B/B
      rPECs. These results strongly suggest that the silver phenotype is caused by the
      mutation of Mitf and that Mitf plays a critical role in rPEC differentiation and
      transdifferentiation.

PMID- 9576829
TI  - The cell cycle program in germ cells of the Drosophila embryo.
AB  - The germ cells of metazoans follow a program of proliferation that is distinct
      from proliferation programs of somatic cells. Despite their developmental
      importance, the cell proliferation program in the metazoan primordial germ cells
      is not well characterized and the regulatory controls are not understood. In
      Drosophila melanogaster, germ cell precursors (called pole cells) proliferate
      early in embryogenesis and then enter a prolonged quiescence. We found that polar
      nuclear divisions are asynchronous and lag behind somatic nuclear divisions
      during syncytial cycles 9 and 10. Thus, the polar division program deviates from
      the somatic division program when pole nuclei and somatic nuclei still share a
      common cytoplasm, earlier than previously thought. The lag in polar nuclear
      divisions is independent of grapes, which is required for lengthening somatic
      cell cycles 10-13. Mapping of the last S phase in pole cells and measurement of
      their DNA content indicate that pole cells become quiescent in G2 phase of the
      cell cycle. We were able to drive quiescent pole cells into mitosis by induction
      of either an activator of Cdc2 (Cdc25string phosphatase) or a mutant form of Cdc2
      that cannot be inhibited by phosphorylation. In contrast, induction of wild-type
      Cdc2 with a mitotic cyclin did not induce mitosis in pole cells. We propose that
      inhibition of Cdc2 by phosphorylation contributes to G2 arrest in pole cells
      during embryogenesis. Furthermore, pole cells enter G1 following induced mitoses,
      indicating that entry into both mitosis and S phase is blocked in quiescent pole
      cells. These studies represent the first molecular characterization of
      proliferation in embryonic germ cells of Drosophila.

PMID- 9576831
TI  - Ectoderm cell--ECM interaction is essential for sea urchin embryo skeletogenesis.
AB  - Paracentrotus lividus sea urchin nectin (Pl-nectin) is an extracellular matrix
      (ECM) protein of the sea urchin embryo on the apical surface of the ectoderm and
      has been shown to be an adhesive substrate for embryonic cells. A monoclonal
      antibody (McAb) to Pl-nectin was generated that inhibits the adhesion of blastula
      cells to Pl-nectin-coated substrates in an in vitro functional assay. To examine
      for possible in vivo functions of Pl-nectin, Fab fragments (Fabs) of Pl-nectin
      McAb were added to early blastulae. Ingression of primary mesenchyme cells was
      not affected by Fabs. As control embryos reached the pluteus stage, treated
      embryos showed a severe inhibition of skeletal elongation and patterning. When
      the Fabs were injected directly into the blastocoel, even at higher concentration
      than was applied externally, skeletogenesis was normal. Therefore, the effect of
      the antibody on spiculogenesis was indirect. The treatment was partially
      reversible as embryos eventually seemed to recover and elongate spicules,
      although with an incorrect patterning. Migration of pigment cells was also
      affected by the Fabs, since they did not disperse throughout the ectoderm but
      remained clustered in ectopic areas. In contrast, the development of endoderm
      structures was not affected. Our results indicate that in the sea urchin embryo
      the appropriate contact of ectodermal cells with outer ECM components is
      essential for the correct morphogenesis of inner mesodermal structures.

PMID- 9576830
TI  - The hybrid histidine kinase dhkB regulates spore germination in Dictyostelium
      discoideum.
AB  - Spore germination is a defined developmental process that marks a critical point
      in the life cycle of Dictyostelium discoideum. Upon germination the environmental
      conditions must be conducive to cell growth to ensure survival of emerged
      amoebae. However, the signal transduction pathways controlling the various
      aspects of spore germination in large part remain to be elucidated. We have used
      degenerate PCR to identify dhkB, a two-component histidine kinase, from D.
      discoideum. DhkB is predicted to be a transmembrane hybrid sensor kinase. The
      dhkB-null cells develop with normal timing to give what seem to be mature
      fruiting bodies by 22 to 24 h. However, over the next several hours, the
      ellipsoidal and encapsulated spores proceed to swell and germinate in situ within
      the sorus and thus do not respond to the normal inhibitors of germination present
      within the sorus. The emerged amoebae dehydrate due to the high osmolarity within
      the sorus, and by 72 h 4% or less of the amoebae remain as spores, while most
      cells are now nonviable. Precocious germination is suppressed by ectopic
      activation of or expression of cAMP-dependent protein kinase A. Additionally, at
      24 h the intracellular concentration of cAMP of dhkB- spores is 40% that of dhkB+
      spores. The results indicate that DHKB regulates spore germination, and a
      functional DHKB sensor kinase is required for the maintenance of spore dormancy.
      DHKB probably acts by maintaining an active PKA that in turn is inhibitory to
      germination.

PMID- 9576832
TI  - Fiber apoptosis in developing rat muscles is regulated by activity, neuregulin.
AB  - Motor neurons are thought to critically regulate the survival of a subset of
      developing muscle fibers. In muscles that develop in the absence of innervation,
      primary muscle fibers appear to form in normal numbers, but their long-term
      survival is thought to require innervation-induced suprathreshold activity. Here
      I examine interactions between motor neurons and muscle fibers in newborn rats. I
      report that a small fraction of muscle fibers in developing muscles undergo
      apoptosis. Many, if not all, of these fibers appear to have lost innervation
      owing to the retraction of nerve terminals. That the apoptosis is initiated by
      the loss of functional innervation is suggested by a severalfold increase in the
      magnitude of fiber apoptosis following denervation and muscle paralysis. Finally,
      both naturally occurring and denervation-induced muscle fiber apoptosis can be
      prevented by exogenous administration of neuregulin. These results argue that the
      survival of all or a subset of developing muscle fibers is ultimately regulated
      by neuregulin. Furthermore, these results suggest a model in which innervation
      induced suprathreshold activity indirectly regulates muscle fiber survival by
      modulating the levels of neuregulin at developing neuromuscular junctions.

PMID- 9576833
TI  - Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary
      epithelial cells in an opposing fashion.
AB  - Elongation and branching of epithelial ducts is a crucial event during the
      development of the mammary gland. Branching morphogenesis of the mouse mammary
      epithelial TAC-2 cell line was used as an assay to examine the role of Wnt, HGF,
      TGF-beta, and the Notch receptors in branching morphogenesis. Wnt-1 was found to
      induce the elongation and branching of epithelial tubules, like HGF and TGF-beta
      2, and to strongly cooperate with either HGF or TGF-beta 2 in this activity. Wnt
      1 displayed morphogenetic activity in TAC-2 cells as it induced branching even
      under conditions that normally promote cyst formation. The Notch4(int-3) mammary
      oncoprotein, an activated form of the Notch4 receptor, inhibited the branching
      morphogenesis normally induced by HGF and TGF-beta 2. The minimal domain within
      the Notch4(int-3) protein required to inhibit morphogenesis consists of the CBF-1
      interaction domain and the cdc10 repeat domain. Coexpression of Wnt-1 and
      Notch4(int-3) demonstrates that Wnt-1 can overcome the Notch-mediated inhibition
      of branching morphogenesis. These data suggest that Wnt and Notch signaling may
      play opposite roles in mammary gland development, a finding consistent with the
      convergence of the wingless and Notch signaling pathways found in Drosophila.

PMID- 9576834
TI  - Knock-in mutation of transcription factor GATA-3 into the GATA-1 locus: partial
      rescue of GATA-1 loss of function in erythroid cells.
AB  - Transcription factors of the GATA-family are essential for proper development of
      diverse tissues or cell types. GATA-1 is required for differentiation of two
      hematopoietic lineages (red blood cells and megakaryocytes), whereas GATA-3 is
      essential for T-cell development. Functional studies suggest that many properties
      of the GATA-family of proteins are shared and largely interchangeable. To test
      whether the function of GATA-1 in erythroid differentiation can be replaced by
      another GATA-factor, we generated a knock-in mutation of the GATA-1 locus in
      which GATA-3 cDNA was introduced by gene targeting. Mutant embryos (designated
      G1G3ki), though embryonic lethal, exhibit partial rescue, characterized by
      increased survival of erythroid precursor cells and improved hemoglobin
      production. The basis for the incomplete extent of rescue is likely to be
      complex, but may be accounted for, in part, by insufficient accumulation of GATA
      3 protein (compared with the normal level of GATA-1). Our findings suggest that
      GATA-3 protein is functional when expressed in an erythroid environment and is
      competent to act on at least a subset of erythroid-expressed target genes in
      vivo.

PMID- 9576835
TI  - The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac
      ventricles independent of left-right sidedness.
AB  - dHAND and eHAND are basic helix-loop-helix transcription factors that play
      critical roles in cardiac development. The HAND genes have a complementary left
      right cardiac asymmetry of expression with dHAND predominantly on the right side
      and eHAND on the left side of the looped heart tube. Here we show that although
      eHAND is asymmetrically expressed along the anterior-posterior and dorsal-ventral
      embryonic axes, it is symmetrically expressed along the left-right axis at early
      stages of embryonic and cardiac development. After cardiac looping, dHAND and
      eHAND are expressed in the right (pulmonary) and left (systemic) ventricles,
      respectively. The left-right (LR) sidedness of dHAND and eHAND expression is
      demonstrated to be anatomically reversed in situs inversus (inv/inv) mouse
      embryos; however, dHAND expression persists in the pulmonary ventricle and eHAND
      in the systemic ventricle regardless of anatomic position, indicating chamber
      specificity of expression. Previously we showed that dHAND-null mice fail to form
      a right-sided pulmonary ventricle. Here mice homozygous for the dHAND and inv
      mutations are demonstrated to have only a right-sided ventricle which is
      morphologically a left (systemic) ventricle. These data suggest that the HAND
      genes are involved in development of segments of the heart tube which give rise
      to specific chambers of the heart during cardiogenesis, rather than controlling
      the direction of cardiac looping by interpreting the cascade of LR embryonic
      signals.

PMID- 9576837
TI  - The Development and Validation of Scales Assessing Students' Achievement Goal
      Orientations
AB  - Achievement goal theory has emerged as a major new direction in motivational
      research. A distinction is made among conceptually different achievement goal
      orientations including the goal to develop ability (task goal orientation), the
      goal to demonstrate ability (ability-approach goal orientation), and the goal to
      avoid the demonstration of lack of ability (ability-avoid goal orientation).
      Scales assessing each of these goal orientations were developed over an eight
      year period by a group of researchers at the University of Michigan. The results
      of studies conducted with seven different samples of elementary and middle school
      students are used to describe the internal consistency, stability, and construct
      validity of the scales. Comparisons of these scales with those developed by
      Nicholls and his colleagues provide evidence of convergent validity. Confirmatory
      factor analysis attests to the discriminant validity of the scales. Copyright
      1998 Academic Press.

PMID- 9576836
TI  - Specific arrest of cardiogenesis in cultured embryonic stem cells lacking Cripto
      1.
AB  - The molecular events of cardiac lineage specification and differentiation are
      largely unknown. Here we describe the involvement of a growth factor with an EGF
      like domain, Cripto-1 (Cr-1), in cardiac differentiation. During embryonic
      development, Cr-1 is expressed in the mouse blastocyst, primitive streak, and
      later is restricted to the developing heart. To investigate the role of Cr-1, we
      have generated Cr-1-negative embryonic stem (ES) cell lines by homologous
      recombination. The resulting double "knockout" ES cells have selectively lost the
      ability to form beating cardiac myocytes, a process that can be rescued by
      reintroducing Cr-1 gene back into the Cr(-/-) cells. Furthermore, the lack of
      functional Cr-1 is correlated with absence of expression of cardiac-specific
      myosin light and heavy chain genes during differentiation. Differentiation into
      other cell types including skeletal muscle is not disrupted. These results
      suggest that Cr-1 is essential for contractile cardiomyocyte formation in vitro.

PMID- 9576838
TI  - Inductive Reasoning in Third Grade: Intervention Promises and Constraints
AB  - The results of two evaluation studies with respect to a programme for enhancing
      inductive reasoning ability of third grade students are presented. The programme
      is a classroom version of the German programme 'Denktraining fur Kinder 1'
      (Cognitive training for children; Klauer, 1989). In the first formative
      evaluation study, two experimental groups with 30 students in total and one
      control group with 9 students were involved. Observations during the lessons, and
      teachers' reports showed that teachers were able to implement the programme. Both
      experimental groups significantly outperformed the control group on a posttest
      immediately after the programme and on a follow-up test 3 1/2 months later.
      Further analyses of the data revealed tentative evidence of the superiority of a
      direct teaching method. In the second summative evaluation study, the same
      programme was applied to a larger sample (experimental groups: n = 99 in total;
      and control groups: n = 232 in total) of third grade students. On the basis of
      Study 1, the programme instructions were slightly changed. The experimental
      groups scored significantly higher on a posttest three months after completion of
      the programme. Copyright 1998 Academic Press.

PMID- 9576839
TI  - Facilitating Knowledge-Based Inferences in Less-Skilled Readers
AB  - The present study replicated Long, Oppy, and Seely's (1994) finding that skilled
      readers make knowledge-based inferences spontaneously during reading whereas less
      skilled readers do not. However, the study also showed that less-skilled readers
      can make knowledge-based inferences with appropriate textual support. Evidence
      for knowledge-based inferences was obtained by examining whether readers were
      faster to make lexical decision responses to theme-appropriate targets (e.g.,
      burglar) than to theme-inappropriate targets (e.g., blueprint), when reading
      short passages (e.g., The old woman awoke to a sound from downstairs. She reached
      into her purse and found only a file.). Whereas skilled readers generated
      knowledge-based inferences under all text conditions, less-skilled readers only
      showed evidence of having generated knowledge-based inferences when the text
      incorporated a question inviting the inference (e.g., The old woman awoke and
      said, 'Why is there a sound downstairs?' She reached into her purse and found
      only a file.) and text-presentation speed was slower. Copyright 1998 Academic
      Press.

PMID- 9576840
TI  - Productivity of Educational Psychologists in Educational Psychology Journals,
      1991-1996
AB  - The scholarly productivity of educational psychologists, indexed in terms of the
      number of papers published in professional journals in the field was the focus of
      this investigation. Five journals considered to be among the "core journals" in
      the field and, thus, those in which educational psychologists are likely to
      publish their scholarship were examined for the years 1991-1996. Both
      institutions (i.e., universities) and individuals were identified. The top-rated
      institution, in terms of educational psychology productivity, was the University
      of Maryland and the most prolific individual contributor to the journals was
      Herbert Marsh. The findings partially replicate several previous productivity
      studies in psychology and educational psychology. The most productive scholars in
      the field include both seasoned, established leaders in the discipline, as well
      as younger individuals who are making their mark. Copyright 1998 Academic Press.

PMID- 9576841
TI  - The Relationship between Motivational Beliefs and Learning Strategy Use among
      Norwegian College Students
AB  - We studied how motivational beliefs were related to learning strategy use in 176
      Norwegian college students who were in the second year of their teacher training.
      Students' implicit theories of intelligence, self-efficacy beliefs, and learning
      strategy use were assessed by self-report instruments. It was found that students
      who conceived of intelligence as a relatively modifiable quality reported using
      more strategies than students who had doubts about the modifiability of
      intelligence. However, the relation between students' theories of intelligence
      and their learning strategy use varied with the way their theories of
      intelligence were assessed, with only indirect questions about the modifiability
      of intelligence yielding a positive relation. Regression analysis and group
      comparisons suggested that beliefs in the modifiability of intelligence may
      override the contribution of self-efficacy to students' use of learning
      strategies. With this study, relations previously emphasized within American
      theory and research are extended to college students in a different cultural
      context. Copyright 1998 Academic Press.

PMID- 9576842
TI  - The Relationship of Psychosocial Maturity to Parenting Quality and Intellectual
      Ability for American and Korean Adolescents
AB  - Psychosocial maturity, gender, intellectual ability, and parenting practices were
      examined with a group of 344 Korean and 214 American adolescents. American
      adolescents reported greater self-reliance, work-orientation, and self-identity
      than did Korean adolescents. In addition, American girls described themselves as
      more mature in work orientation than did American boys, a trend reversed in the
      Korean culture. Intellectual ability was associated with adolescents'
      psychosocial maturity. Differences in parenting style were predictive of
      psychosocial maturity regardless of ethnic group membership. Authoritative
      parenting, compared to all other styles, was related to significantly higher
      means in adolescent maturity. Authoritarian and neglectful styles were almost
      always associated with lower psychosocial maturity, whereas permissive and mixed
      parenting styles were more advantageous than either authoritarian or neglectful
      parenting. Copyright 1998 Academic Press.

PMID- 9576844
TI  - Neuropathy target esterase and a homologous Drosophila neurodegeneration
      associated mutant protein contain a novel domain conserved from bacteria to man.
AB  - The N-terminal amino acid sequences of proteolytic fragments of neuropathy target
      esterase (NTE), covalently labelled on its active-site serine by a biotinylated
      organophosphorus ester, were determined and used to deduce the location of this
      serine residue and to initiate cloning of its cDNA. A putative NTE clone,
      isolated from a human foetal brain cDNA library, encoded a 1327 residue
      polypeptide with no homology to any known serine esterases or proteases. The
      active-site serine of NTE (Ser-966) lay in the centre of a predicted hydrophobic
      helix within a 200-amino-acid C-terminal domain with marked similarity to
      conceptual proteins in bacteria, yeast and nematodes; these proteins may comprise
      a novel family of potential serine hydrolases. The Swiss Cheese protein which,
      when mutated, leads to widespread cell death in Drosophila brain [Kretzschmar,
      Hasan, Sharma, Heisenberg and Benzer (1997) J. Neurosci. 17, 7425-7432], was
      strikingly homologous to NTE, suggesting that genetically altered NTE may be
      involved in human neurodegenerative disease.

PMID- 9576845
TI  - Rac1, and not Rac2, is involved in the regulation of the intracellular hydrogen
      peroxide level in HepG2 cells.
AB  - In order to elucidate the components of the oxygen sensory complex in HepG2 cells
      which regulates the production of erythropoietin, we have microinjected
      recombinant variants of the human small GTP-binding protein hRac1 and measured
      their effects on the production of reactive oxygen species (ROS) by the
      dihydrorhodamine-123 technique. The dominant-negative mutant hRac1(T17N) inhibits
      the NADH-stimulated production of ROS in HepG2 cells, whereas the constitutively
      activated hRac1(G12V) leads to an increase in intracellular ROS concentration.
      Reverse transcriptase PCR analysis showed that the hRac1, but not the hRac2, gene
      is expressed in HepG2 cells. These results demonstrate that hRac1, and not hRac2,
      is involved in the regulation of ROS production in HepG2 cells and suggest that
      hRac1 specifically functions in the non-phagocytic NAD(P)H oxidase complex.

PMID- 9576846
TI  - Reactions of nitric oxide with mitochondrial cytochrome c: a novel mechanism for
      the formation of nitroxyl anion and peroxynitrite.
AB  - The aerobic reactions of nitric oxide with cytochrome c were analysed. Nitric
      oxide (NO) reacts with ferrocytochrome c at a rate of 200 M-1 s-1 to form
      ferricytochrome c and nitroxyl anion (NO-). Ferricytochrome c was detected by
      optical spectroscopy; NO- was detected by trapping with metmyoglobin (Mb3+) to
      form the EPR-detectable Mb-nitrosyl complex, and by the formation of dimers in
      yeast ferrocytochrome c via cross-linking of the free cysteine residue. The NO-
      formed subsequently reacted with oxygen to form peroxynitrite, as measured by the
      oxidation of dihydrorhodamine 123. NO binds to ferricytochrome c to form the
      ferricytochrome c-NO complex. The on-rate for this reaction is 1.3+/-0.4x10(3) M
      1.s-1, and the off-rate is 0.087+/-0.054 s-1. The dissociation constant (Kd) of
      the complex is 22+/-7 microM. These reactions of NO with cytochrome c are likely
      to be relevant to mitochondrial metabolism of NO. Ferricytochrome c can act as a
      reversible sink for excess NO in the mitochondria. The reduction of NO to NO- by
      ferrocytochrome c may play a role in the irreversible inhibition of mitochondrial
      oxygen consumption by peroxynitrite. It is generally assumed that peroxynitrite
      would be formed in mitochondria via the reaction of NO with superoxide. The
      finding that NO- is formed from the reaction of NO and ferrocytochrome c provides
      a means of producing peroxynitrite in the absence of superoxide, via the reaction
      of NO- with oxygen.

PMID- 9576847
TI  - Molecular cloning, expression and catalytic activity of a human AKR7 member of
      the aldo-keto reductase superfamily: evidence that the major 2
      carboxybenzaldehyde reductase from human liver is a homologue of rat aflatoxin B1
      aldehyde reductase.
AB  - The masking of charged amino or carboxy groups by N-phthalidylation and O
      phthalidylation has been used to improve the absorption of many drugs, including
      ampicillin and 5-fluorouracil. Following absorption of such prodrugs, the
      phthalidyl group is hydrolysed to release 2-carboxybenzaldehyde (2-CBA) and the
      pharmaceutically active compound; in humans, 2-CBA is further metabolized to 2
      hydroxymethylbenzoic acid by reduction of the aldehyde group. In the present
      work, the enzyme responsible for the reduction of 2-CBA in humans is identified
      as a homologue of rat aflatoxin B1-aldehyde reductase (rAFAR). This novel human
      aldo-keto reductase (AKR) has been cloned from a liver cDNA library, and together
      with the rat protein, establishes the AKR7 family of the AKR superfamily. Unlike
      its rat homologue, human AFAR (hAFAR) appears to be constitutively expressed in
      human liver, and is widely expressed in extrahepatic tissues. The deduced human
      and rat protein sequences share 78% identity and 87% similarity. Although the two
      AKR7 proteins are predicted to possess distinct secondary structural features
      which distinguish them from the prototypic AKR1 family of AKRs, the catalytic-
      and NADPH-binding residues appear to be conserved in both families. Certain of
      the predicted structural features of the AKR7 family members are shared with the
      AKR6 beta-subunits of voltage-gated K+-channels. In addition to reducing the
      dialdehydic form of aflatoxin B1-8,9-dihydrodiol, hAFAR shows high affinity for
      the gamma-aminobutyric acid metabolite succinic semialdehyde (SSA) which is
      structurally related to 2-CBA, suggesting that hAFAR could function as both a SSA
      reductase and a 2-CBA reductase in vivo. This hypothesis is supported in part by
      the finding that the major peak of 2-CBA reductase activity in human liver co
      purifies with hAFAR protein.

PMID- 9576848
TI  - Hydroxylated naphthoquinones as substrates for Escherichia coli anaerobic
      reductases.
AB  - We have used two hydroxylated naphthoquinol menaquinol analogues, reduced
      plumbagin (PBH2, 5-hydroxy-2-methyl-1,4-naphthoquinol) and reduced lapachol
      [LPCH2, 2-hydroxy-3-(3-methyl-2-butenyl)-1, 4-naphthoquinol], as substrates for
      Escherichia coli anaerobic reductases. These compounds have optical, solubility
      and redox properties that make them suitable for use in studies of the enzymology
      of menaquinol oxidation. Oxidized plumbagin and oxidized lapachol have well
      resolved absorbances at 419 nm (epsilon=3.95 mM-1. cm-1) and 481 nm (epsilon=2.66
      mM-1.cm-1) respectively (in Mops/KOH buffer, pH 7.0). PBH2 is a good substrate
      for nitrate reductase A (Km=282+/-28 microM, kcat=120+/-6 s-1) and fumarate
      reductase (Km=155+/-24 microM, kcat=30+/-2 s-1), but not for DMSO reductase.
      LPCH2 is a good substrate for nitrate reductase A (Km=57+/-35 microM, kcat=68+/
      13 s-1), fumarate reductase (Km=85+/-27 microM, kcat=74+/-6 s-1) and DMSO
      reductase (Km=238+/-30 microM, kcat=191+/-21 s-1). The sensitivity of enzymic
      LPCH2 and PBH2 oxidation to 2-n-heptyl-4-hydroxyquinoline N-oxide inhibition is
      consistent with their oxidation occurring at sites of physiological quinol
      binding.

PMID- 9576849
TI  - Molecular analysis of H2O2-induced senescent-like growth arrest in normal human
      fibroblasts: p53 and Rb control G1 arrest but not cell replication.
AB  - Human diploid fibroblasts lose the capacity to proliferate and enter a state
      termed replicative senescence after a finite number of cell divisions in culture.
      When treated with sub-lethal concentrations of H2O2, pre-senescent human
      fibroblasts enter long-term growth arrest resembling replicative senescence. To
      understand the molecular basis for the H2O2-induced growth arrest, we determined
      the cell cycle distribution, levels of p53 tumour suppressor and p21 cyclin
      dependent kinase inhibitor proteins, and the status of Rb phosphorylation in H2O2
      treated cells. A 2-h pulse of H2O2 arrested the growth of IMR-90 fetal lung
      fibroblasts for at least 15 days. The arrested cells showed a G1 DNA content. The
      level of p53 protein increased 2- to 3-fold within 1.5 h after H2O2 exposure but
      returned to the control level by 48 h. The induction of p53 protein was dose
      dependent, beginning at 50-75 microM and reaching a maximum at 100-250 microM.
      The induction of p53 did not appear to correlate with the level of DNA damage as
      measured by the formation of 8-oxo-2'-deoxyguanosine in DNA. The level of p21
      protein increased about 18 h after H2O2 exposure and remained elevated for at
      least 21 days. During this period, Rb remained underphosphorylated. The induction
      of p53 by H2O2 was abolished by the iron chelator deferoxamine and the protein
      synthesis inhibitor cycloheximide. The human papillomavirus protein E6, when
      introduced into the cells, abolished the induction of p53, reduced the induction
      of p21 to a minimal level and allowed Rb phosphorylation and entry of the cells
      into S-phase. The human papillomavirus protein E7 reduced the overall level of Rb
      and also abolished H2O2-induced G1 arrest. Inactivating G1 arrest by E6, E7 or
      both did not restore the replicative ability of H2O2-treated cells. Thus H2O2
      treated cells show a transient elevation of p53, high level of p21, lack of Rb
      phosphorylation, G1 arrest and inability to replicate when G1 arrest is
      inactivated.

PMID- 9576850
TI  - Characterization of the UDP-glucuronosyltransferase isoenzyme expressed in rat
      ovary and its regulation by gonadotropins.
AB  - Earlier studies have demonstrated that phenol UDP-glucuronosyltransferase (UGT)
      activity is up-regulated by pregnant mare's serum gonadotropin (PMSG) in rat
      ovary, but not liver. This phenomenon was investigated in more detail in the
      present study. Ovaries and livers of immature rats, rats synchronized with
      respect to their preovulatory and corpus luteal phases by treatment with PMSG,
      and mature rats hyperstimulated with PMSG were compared. Under all of these
      conditions, only one immunoreactive band of UGT, shown to be phenol UGT, was
      detected in the rat ovary. The effects of oestradiol, progesterone and/or human
      chorionic gonadotropin (hCG) on the level of phenol UGT in immature rat ovary
      were also examined. Partial up-regulation was caused by progesterone or
      oestradiol, together with hCG, whereas progesterone or oestradiol alone had no up
      regulating effect. Follicle-stimulating hormone also seemed to be required for
      the up-regulation in ovaries enriched in corpus luteum. The present findings
      demonstrate that progesterone is involved in the regulation of phenol UGT in rat
      ovary by gonadotropins. Regulation by both progesterone and oestradiol was
      dependent on induction of ovulation and steroidogenesis by luteinizing hormone.

PMID- 9576851
TI  - High-density lipoprotein (HDL3)-associated alpha-tocopherol is taken up by HepG2
      cells via the selective uptake pathway and resecreted with endogenously
      synthesized apo-lipoprotein B-rich lipoprotein particles.
AB  - alpha-Tocopherol (alphaTocH) is transported in association with lipoproteins in
      the aqueous milieu of the plasma. Although up to 50% of circulating alphaTocH is
      transported by high-density lipoproteins (HDLs), little is known about the
      mechanisms of uptake of HDL-associated alphaTocH. During the current study, human
      apolipoprotein (apo)E-free HDL subclass 3 (HDL3) labelled with [14C]alphaTocH was
      used to investigate uptake mechanisms of HDL3-associated alphaTocH by a permanent
      hepatoblastoma cell line (HepG2). HDL3-associated alphaTocH was taken up
      independently of HDL3 holoparticles in excess of apoA-I comparable with the non
      endocytotic delivery of cholesteryl esters to cells termed the 'selective'
      cholesteryl ester uptake pathway. Experiments with unlabelled HDL3 demonstrated
      net mass transfer of alphaTocH to HepG2 cells. Time-dependent studies with
      [14C]alphaTocH-labelled HDL3 revealed tracer uptake in 80-fold excess of apoA-I
      and in 4-fold excess of cholesteryl linoleate. In addition to HLDs, low-density
      lipoprotein (LDL)-associated alphaTocH was also taken up in excess of
      holoparticles, although to a lesser extent. These findings were confirmed with
      unlabelled lipoprotein preparations, in which HDL3 displayed a 2- to 3-fold
      higher alphaTocH donor efficiency than LDLs (lipoproteins adjusted for equal
      amounts of alphaTocH). An important factor affecting particle-independent uptake
      of alphaTocH was the cellular cholesterol content (a 2-fold increase in cellular
      cholesterol levels resulted in a 2.3-fold decrease in uptake). Pulse-chase
      studies demonstrated that some of the HDL3-associated alphaTocH taken up
      independently of holoparticle uptake was resecreted along with a newly
      synthesized apoB-containing lipoprotein fraction.

PMID- 9576852
TI  - Structural and spectroscopic studies of azide complexes of horse heart myoglobin
      and the His-64-->Thr variant.
AB  - The high-resolution X-ray crystallographic structures of horse heart
      azidometmyoglobin complexes of the wild-type protein and the His-64-->Thr variant
      have been determined to 2.0 and 1.8 A respectively. Azide binds to wild-type
      metmyoglobin in a bent configuration with an Fe-N-1-N-3 angle of 119 degrees and
      is oriented into the distal crevice in the direction of Ile-107. The proximity of
      the His-64 NE2 atom to the N-1 atom of the bound azide indicates stabilization of
      the ligand by the His-64 side chain through hydrogen bonding. In addition,
      structural characterization of wild-type horse heart azidometmyoglobin
      establishes that the only structural change induced by ligand binding is a small
      movement of the Leu-29 side chain away from the azide ligand. EPR and Fourier
      transform infrared spectroscopy were used to characterize the myoglobin azide
      complexes further. EPR spectroscopy revealed that, in contrast with wild-type
      azidometmyoglobin, two slightly different low-spin species are formed by azide
      bound to the His-64-->Thr variant both in solution and in a polycrystalline
      sample. One of these low-spin species has a greater relative intensity, with g
      values very similar to those of the azide complex of the wild-type protein. These
      EPR results together with structural information on this variant indicate the
      presence of two distinct conformations of bound azide, with one form
      predominating. The major conformation is comparable to that formed by wild-type
      myoglobin in which azide is oriented into the distal crevice. In the minor
      conformation the azide is oriented towards the exterior of the protein.

PMID- 9576853
TI  - An esterase from Escherichia coli with a sequence similarity to hormone-sensitive
      lipase.
AB  - An esterase from Escherichia coli that is a member of the hormone-sensitive
      lipase (HSL) family was overproduced, purified and characterized. It is encoded
      by the ybaC gene and composed of 319 amino acid residues with an Mr of 36038. The
      enzymic activity was determined by using various p-nitrophenyl esters of fatty
      acids as a substrate at 25 degreesC and pH 7.1. The enzyme showed hydrolytic
      activity towards substrates with an acyl chain length of less than 8, whereas it
      showed little hydrolytic activity towards those with an acyl chain length of more
      than 10. In addition, it showed little hydrolytic activity towards
      trioleoylglycerol and cholesterol oleate. Determination of the kinetic parameters
      for the hydrolyses of the substrates from C2 to C8 indicates that C4 and C5
      substrates are the most preferred. Close agreement between the Mr determined by
      SDS/PAGE (37000) and column chromatography (38000) suggests that the enzyme
      exists in a monomeric form. It is an acidic protein with a pI value of 4.1. The
      far-UV CD spectrum suggests that its helical content is 26.1%. Comparison of the
      amino acid sequence of this enzyme with those involved in the HSL family allows
      us to propose that Ser165, Asp262 and His292 constitute the catalytic triad of E.
      coli esterase.

PMID- 9576854
TI  - Spectrin self-association site: characterization and study of beta-spectrin
      mutations associated with hereditary elliptocytosis.
AB  - Most of hereditary elliptocytosis (HE) cases are related to a spectrin dimer
      (SpD) self-association defect. The severity of haemolysis is correlated with the
      extent of the SpD self-association defect, which itself depends on the location
      of the mutation regarding the tetramerization site. This site is presumed to
      involve the first C helix of the alpha chain and the last two helices, A and B,
      of the beta chain to reconstitute a triple helical structure (A, B and C), as
      observed along spectrin. Using recombinant peptides, we demonstrated that the
      first C helix of the alpha chain and the last two helices of the beta chain alone
      are not sufficient to establish interactions, which only occurred when a complete
      triple-helical repeat was added to each partner. One adjacent repeat is necessary
      to stabilize the conformation of both N- and C-terminal structures directly
      involved in the interaction site and is sufficient to generate a binding affinity
      similar to that observed in the native molecule. Producing peptides carrying a
      betaHE mutation, we reproduced the tetramerization defect as observed in
      patients. Therefore, the betaW2024R and betaW2061R mutations, which replace the
      invariant tryptophan and a residue located in the hydrophobic core, respectively,
      affect alpha-beta interactions considerably. In contrast, the betaA2013V
      mutation, which modifies a residue located outside any presumed interacting
      regions, has a minor effect on the interaction.

PMID- 9576855
TI  - Reactivation of triosephosphate isomerase from three trypanosomatids and human:
      effect of suramin.
AB  - The reactivation of the homodimeric triosephosphate isomerases (TIMs) from
      Trypanosoma brucei, T. cruzi, Leishmania mexicana and humans was determined after
      their denaturation with guanidine hydrochloride. In the range of 2-32 microg of
      T. brucei TIM per ml and 0.2-5 microg of the other enzymes per ml, the rate and
      extent of TIM reactivation depended on protein concentration, indicating that at
      these protein concentrations, the rate-limiting step of reactivation is monomer
      association and not monomer folding. The rate of monomer association was more
      than one order of magnitude lower in the T. brucei enzyme than in the other three
      enzymes. Suramin is a drug of choice in the treatment of sleeping sickness, but
      its mechanism of action is not known. At micromolar concentrations, Suramin
      inhibited the reactivation of the four enzymes, but the extent of inhibition by
      Suramin decreased with increasing protein concentration as consequence of a
      diminution of the life time of the folded monomer. Since the life time of the
      monomer of T. brucei TIM is longer than that of the other enzymes, Suramin is a
      more effective inhibitor of the reactivation of TIM from T. brucei, particularly
      at monomer concentrations above 1 microg of protein per ml (monomer concentration
      approx. 37 nM). Compounds that are structurally related to Suramin also inhibit
      TIM reactivation; their effect was about five times more pronounced in the enzyme
      from T. brucei than in human TIM.

PMID- 9576856
TI  - Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione
      transferases.
AB  - Human glutathione transferases (GSTs) from Alpha (A), Mu (M) and Theta (T)
      classes exhibited glutathione peroxidase activity towards phospholipid
      hydroperoxide. The specific activities are in the order: GST A1-1>GST T1-1>GST M1
      1>GST A2-2>GST A4-4. Using a specific and sensitive HPLC method, specific
      activities towards the phospholipid hydroperoxide,1-palmitoyl-2-(13-hydroper oxy
      cis-9, trans-11 -octadecadienoyl)-l-3-phosphatidylcholine (PLPC-OOH) were
      determined to be in the range of 0.8-20 nmol/min per mg of protein. Two human
      class Pi (P) enzymes (GST P1-1 with Ile or Val at position 105) displayed no
      activity towards the phospholipid hydroperoxide. Michaelis-Menten kinetics were
      followed only for glutathione, whereas there was a linear dependence of rate with
      PLPC-OOH concentration. Unlike the selenium-dependent phospholipid hydroperoxide
      glutathione peroxidase (Se-PHGPx), the presence of detergent inhibited the
      activity of GST A1-1 on PLPC-OOH. Also, in contrast with Se-PHGPx, only
      glutathione could act as the reducing agent for GST A1-1. A GST A1-1 mutant
      (Arg15Lys), which retains the positive charge between the GSH- and hydrophobic
      binding sites, exhibited a decreased kcat for PLPC-OOH but not for CDNB,
      suggesting that the correct topography of the GSH site is more critical for the
      phospholipid substrate. A Met208Ala mutation, which gives a modified hydrophobic
      site, decreased the kcat for CDNB and PLPC-OOH by comparable amounts. These
      results indicate that Alpha, Mu and Theta class human GSTs provide protection
      against accumulation of cellular phospholipid hydroperoxides.

PMID- 9576857
TI  - Release of the glycosylphosphatidylinositol-anchored enzyme ecto-5'-nucleotidase
      by phospholipase C: catalytic activation and modulation by the lipid bilayer.
AB  - Many hydrolytic enzymes are attached to the extracellular face of the plasma
      membrane of eukaryotic cells by a glycosylphosphatidylinositol (GPI) anchor.
      Little is currently known about the consequences for enzyme function of anchor
      cleavage by phosphatidylinositol-specific phospholipase C. We have examined this
      question for the GPI-anchored protein 5'-nucleotidase (5'-ribonucleotide
      phosphohydrolase; EC 3.1.3.5), both in the native lymphocyte plasma membrane, and
      following purification and reconstitution into defined lipid bilayer vesicles,
      using Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (PI
      PLC). Membrane-bound, detergent-solubilized and cleaved 5'-nucleotidase all
      obeyed Michaelis-Menten kinetics, with a Km for 5'-AMP in the range 11-16 microM.
      The GPI anchor was removed from essentially all 5'-nucleotidase molecules,
      indicating that there is no phospholipase-resistant pool of enzyme. However, the
      phospholipase was much less efficient at cleaving the GPI anchor when 5'
      nucleotidase was present in detergent solution, dimyristoyl phosphatidylcholine,
      egg phosphatidylethanolamine and sphingomyelin, compared with the native plasma
      membrane, egg phosphatidylcholine and a sphingolipid/cholesterol-rich mixture.
      Lipid molecular properties and bilayer packing may affect the ability of PI-PLC
      to gain access to the GPI anchor. Catalytic activation, characterized by an
      increase in Vmax, was observed following PI-PLC cleavage of reconstituted 5'
      nucleotidase from vesicles of several different lipids. The highest degree of
      activation was noted for 5'-nucleotidase in egg phosphatidylethanolamine. An
      increase in Vmax was also noted for a sphingolipid/cholesterol-rich mixture, the
      native plasma membrane and egg phosphatidylcholine, whereas vesicles of
      sphingomyelin and dimyristoyl phosphatidylcholine showed little activation. Km
      generally remained unchanged following cleavage, except in the case of the
      sphingolipid/cholesterol-rich mixture. Insertion of the GPI anchor into a lipid
      bilayer appears to reduce the catalytic efficiency of 5'-nucleotidase, possibly
      via a conformational change in the enzyme, and activity is restored on release
      from the membrane.

PMID- 9576858
TI  - Proteasome and thiol involvement in quality control of
      glycosylphosphatidylinositol anchor addition.
AB  - Improperly processed secretory proteins are degraded by a hydrolytic system that
      is associated with the endoplasmic reticulum (ER) and appears to involve re
      export of lumenal proteins into the cytoplasm for ultimate degradation by the
      proteasome. The chimaeric protein hGHDAF28, which contains a crippled
      glycosylphosphatidylinositol (GPI) C-terminal signal peptide, is degraded by a
      pathway highly similar to that for other ER-retained proteins and is
      characterized by formation of disulphide-linked aggregates, failure to reach the
      Golgi complex and intracellular degradation with a half life of approximately 2
      h. Here we show that N-acetyl-leucinal-leucinal-norleucinal, MG-132 and
      lactacystin, all inhibitors of the proteasome, protect hGHDAF28; hGHDAF28 is
      still proteolytically cleaved in the presence of lactacystin or MG-132, by the
      removal of approximately 2 kDa, but the truncated fragment is not processed
      further. We demonstrate that the ubiquitination system accelerates ER-degradation
      of hGHDAF28, but is not essential to the process. Overall, these findings
      indicate that GPI quality control is mediated by the cytoplasmic proteasome. We
      also show that the presence of a cysteine residue in the GPI signal of hGHDAF28
      is required for retention and degradation, as mutation of this residue to serine
      results in secretion of the fusion protein, implicating thiol-mediated retention
      as a mechanism for quality control of some GPI signals. Removal of the cysteine
      also prevents inclusion of hGHDAF28 in disulphide-linked aggregates, indicating
      that aggregate formation is an additional retention mechanism for this class of
      protein. Therefore our data suggest that an unpaired terminal cysteine is the
      retention motif of the hGHDAF28 GPI-processing signal and that additional
      information may be required for efficient engagement of ER quality control
      systems by the majority of GPI signals which lack cysteine residues.

PMID- 9576859
TI  - Functional studies of the rabbit intestinal Na+/glucose carrier (SGLT1) expressed
      in COS-7 cells: evaluation of the mutant A166C indicates this region is important
      for Na+-activation of the carrier.
AB  - We have exploited two mutants of the rabbit intestinal Na+/glucose carrier SGLT1
      to explore the structure/function relationship of this Na+/glucose transporter in
      COS-7 cells. A functional N-terminal myc-epitope-tagged SGLT1 protein was
      constructed and used to determine the plasma-membrane localization of SGLT1. The
      kinetic and specificity characteristics of the myc-tagged SGLT1 mutant were
      identical with those of wild-type SGLT1. Immunogold labelling and electron
      microscopy confirmed the topology of the N-terminal region to be extracellular.
      Expression of the SGLT1 A166C mutant in these cells showed diminished levels of
      Na+-dependent alpha-methyl-d-glucopyranoside transport activity compared with
      wild-type SGLT1. For SGLT1 A166C, Vmax was 0.92+/-0.08 nmol/min per mg of protein
      and Km was 0.98+/-0.13 mM; for wild-type SGLT1, Vmax was 1.98+/-0.47 nmol/min per
      mg of protein and Km was 0.36+/-0.16 mM. Significantly, phlorrhizin (phloridzin)
      binding experiments confirmed equal expression of Na+-dependent high-affinity
      phlorrhizin binding to COS-7 cells expressing SGLT1 A166C or wild-type SGLT1
      (Bmax 1.55+/-0.18 and 1.69+/-0.57 pmol/mg of protein respectively); Kd values
      were 0.46+/-0.15 and 0.51+/-0.11 microM for SGLT1 A166C and wild-type SGLT1
      respectively. The specificity of sugar interaction was unchanged by the A166C
      mutation. We conclude that the replacement of an alanine residue by cysteine at
      position 166 has a profound effect on transporter function, resulting in a
      decrease in transporter turnover rate by a factor of 2. Taken as a whole the
      functional changes observed by SGLT1 A166C are most consistent with the mutation
      having caused an altered Na+ interaction with the transporter.

PMID- 9576860
TI  - Polyclonal antibody catalytic variability.
AB  - We have performed a systematic variability study of polyclonal antibody catalysis
      by using five rabbits immunized with the same hapten. Important results from this
      work are the following. (1) Similarities were observed in the catalytic
      polyclonal antibodies derived from all five rabbits. Four of the five rabbits
      produced polyclonal samples that were nearly the same in terms of catalytic
      activity, whereas the fifth rabbit, designated as rabbit 2, displayed a somewhat
      higher level of catalytic activity. The catalytic activities (as kcat/kuncat) of
      these polyclonal samples were similar to that from the best murine monoclonal
      antibody that had been previously elicited by the same hapten. (2) Titre was not
      an accurate indicator of polyclonal antibody catalytic activity. (3) A
      mathematical analysis to describe a distribution of Michaelis-Menten catalysts
      was performed to help interpret our results. (4) Kinetic analysis indicated that
      the binding parameters of the different samples were remarkably homogeneous,
      because one or two components were all that were required to fit the on-rate and
      off-rate data satisfactorily. Interestingly, the most active catalytic polyclonal
      sample, that from rabbit 2, displayed the slowest off-rate (so slow it could not
      be measured) and thus the highest overall affinity. (5) Catalytic analysis of
      eluted fractions of antibody from a substrate column indicated that each
      polyclonal sample was also relatively homogeneous in terms of catalytic
      parameters. The main conclusion of our study is that for this hapten-animal
      system, the overall catalytic immune response is relatively consistent at two
      levels. Consistent catalytic activity was observed between the polyclonal samples
      elicited in the different animals, and the elicited hapten-specific polyclonal
      antibodies were relatively homogeneous in terms of binding and catalytic
      parameters within each immunized animal. The observed similarities of the
      catalytic activity in the different animals is surprising, because the immune
      response is based on specific binding of antibodies to hapten. There is no known
      selective pressure to maintain consistent levels of catalytic activity. Our
      results can therefore be interpreted as providing evidence that for this hapten
      there is a fixed relationship between hapten structure and catalytic activity
      and/or consistent genetic factors that dominate the catalytic immune response.

PMID- 9576861
TI  - Structural/functional properties of a mammalian multi-component structure
      containing all major spliceosomal small nuclear ribonucleoprotein particles.
AB  - An approx. 40 S multi-component structure, consisting of all major spliceosomal
      small nuclear ribonucleoprotein particles (snRNP) (U1, U2, U4/U6 and U5) in
      stable association with a large number of polypeptides, mainly in the range 50
      210 kDa, has been reported to exist within rat liver nuclear extracts [Guialis,
      Moraitou, Patrinou-Georgoula and Dangli (1991) Nucleic Acids Res. 19, 287-296].
      Using a new polyclonal antibody recognizing a 63 kDa protein component of the
      complex, this multi-snRNP assembly was detected within rat liver nuclear extracts
      as efficiently as with the antibody for the U2 snRNP-specific B' polypeptide. The
      63 kDa protein was found to correspond to the 66 kDa subunit of the splicing
      factor SF3a, a known integral component of the HeLa 17 S U2 snRNP. Anti-2,2,7
      trimethylguanosine affinity chromatography was an easy and efficient way of
      purifying the multi-snRNP complex from rat liver 40 S heterogeneous nuclear
      ribonucleoprotein particle (hnRNP)-containing sucrose gradient fractions. By
      subsequent glycerol-gradient sedimentation, all known snRNP forms active in RNA
      splicing were identified among its constituents. A complex structurally similar
      to the rat multi-snRNP was also identified in HeLa nuclear extracts. Preservation
      of hnRNP-snRNP interactions was observed within HeLa 40 S fractions. Moreover,
      these fractions were capable of restoring splicing activity when applied in
      reconstitution studies to supplement a micrococcal nuclease-treated splicing
      extract.

PMID- 9576862
TI  - Characterization and sequence of the Chryseobacterium (Flavobacterium)
      meningosepticum carbapenemase: a new molecular class B beta-lactamase showing a
      broad substrate profile.
AB  - The metallo-beta-lactamase produced by Chryseobacterium (formerly Flavobacterium)
      meningosepticum, which is the flavobacterial species of greatest clinical
      relevance, was purified and characterized. The enzyme, named BlaB, contains a
      polypeptide with an apparent Mr of 26000, and has a pI of 8.5. It hydrolyses
      penicillins, cephalosporins (including cefoxitin), carbapenems and 6-beta
      iodopenicillanate, a mechanism-based inactivator of active-site serine beta
      lactamases. The enzyme was inhibited by EDTA, 1-10 phenanthroline and pyridine
      2,6-dicarboxylic acid, with different inactivation parameters for each chelating
      agent. The C. meningosepticum blaB gene was cloned and sequenced. According to
      the G+C content and codon usage, the blaB gene appeared to be endogenous to the
      species. The BlaB enzyme showed significant sequence similarity to other class B
      beta-lactamases, being overall more similar to members of subclass B1, which
      includes the metallo-enzymes of Bacillus cereus (Bc-II) and Bacteroides fragilis
      (CcrA) and the IMP-1 enzyme found in various microbial species, and more
      distantly related to the metallo-beta-lactamases of Aeromonas spp. (CphA, CphA2
      and ImiS) and of Stenotrophomonas maltophilia (L1).

PMID- 9576863
TI  - Saccharomyces cerevisiae GPI10, the functional homologue of human PIG-B, is
      required for glycosylphosphatidylinositol-anchor synthesis.
AB  - An increasing number of plasma membrane proteins have been shown to be attached
      to the membrane via a glycosylphosphatidylinositol (GPI) moiety. All eukaryotes
      share a highly conserved GPI-core structure EthN-P-Man3-GlcN-PI, where EthN is
      ethanolamine. We have identified a protein encoded by the yeast open reading
      frame YGL142C that shares 33% identity with the human Pig-B protein. Deletion of
      this essential gene leads to a block in GPI anchor biosynthesis. We therefore
      named the gene GPI10. Gpi10p and Pig-B are functional homologues and the lethal
      deletion of GPI10 can be rescued by expression of the PIG-B cDNA. As found for
      PIG-B mutant cells, gpi10 deletant cells cannot attach the third mannose in an
      alpha-1,2 linkage to the GPI core-structure intermediate. Overexpression of GPI10
      gives partial resistance to the GPI-synthesis inhibitor YW3548, suggesting that
      this gene product may affect the target of the inhibitor.

PMID- 9576864
TI  - Complementation studies with co-expressed fragments of human red cell band 3
      (AE1): the assembly of the anion-transport domain in xenopus oocytes and a cell
      free translation system.
AB  - We examined the assembly of the membrane domain of the human red cell anion
      transporter (band 3; AE1) by co-expression of recombinant N- and C-terminal
      fragments in Xenopus oocytes and in cell-free translation with canine pancreatic
      microsomes. Co-immunoprecipitation was performed in non-denaturing detergent
      solutions using antibodies directed against the N- and C-termini of the membrane
      domain. Eleven of the twelve fragments were expressed stably in oocytes in the
      presence or absence of their respective partners. However, the fragment
      containing from putative span nine to the C-terminus could be detected in oocytes
      only when co-expressed with its complementary partner containing the first eight
      spans. Co-expression of pairs of fragments divided in the first, second, third
      and fourth exofacial loops and in the fourth cytoplasmic loop resulted in a
      concentration-dependent association, but a pair of fragments divided in the sixth
      cytoplasmic loop did not co-immunoprecipitate. When two complementary fragments
      were translated separately in the cell-free system and the purified microsomes
      were then mixed, co-immunoprecipitation was observed only if the membranes were
      first fused using polyethylene glycol. This shows that co-immunoprecipitation
      results from specific interactions within the membrane and is not an artefact of
      detergent solubilization or immunoprecipitation. We demonstrate that band 3
      assembly can occur within the membrane after translation, insertion and initial
      folding of the individual fragments have been completed. We conclude that most
      band 3 fragments contain the necessary information to fold in the membrane and
      adopt a structure that is sufficiently similar to the native protein that it
      permits correct assembly with its complementary partner.

PMID- 9576866
TI  - Molecular basis of bovine red-cell protein 4.2 polymorphism in Japanese black
      cattle.
AB  - Cattle were divided into three groups according to the red cell-protein 4.2
      (P4.2) phenotypes P4.2(76), P4.2(75) and P4. 2(76/75), whose red cells contained
      Mr 76000 (P4.2/76), 75000 (P4. 2/75) and both 76000 and 75000 isoforms
      respectively. To elucidate the molecular basis that underlies the diversity of
      P4.2, the gene structures of bovine P4.2/76 and P4.2/75 were investigated. Two
      P4.2 cDNA clones were isolated from bone-marrow cDNAs of the animal with the
      P4.2(76/75) phenotype. These were identical in size (2.2 kb), encoding major
      erythroid P4.2 with 687 amino acids, but were different in three nucleotides,
      resulting in changes of amino acids at the 599th, 601st and 627th residues.
      Analysis of genomic DNA from the three phenotypes demonstrated that these two
      clones were derived from gene transcripts by which P4.2/76 and/or P4.2/75 were
      produced. In vitro transcription and translation of P4.2/76 and P4.2/75 cDNAs
      indeed generated P4.2/76 and P4.2/75 identical in size to the red-cell proteins.
      These findings demonstrated that polymorphism of the P4.2 gene at codons 599, 601
      and 627 of P4.2 cDNA was the cause of the molecular diversity of bovine red-cell
      P4.2. Although distinct electrophoretic mobilities suggested a structural
      difference in the two isoforms, this polymorphism appeared to have little effect
      at least on P4.2 association with band 3, since no significant difference was
      observed in the amount of P4.2 relative to total membrane proteins despite the
      phenotype difference for P4.2.

PMID- 9576865
TI  - Platelet sarco/endoplasmic reticulum Ca2+ATPase isoform 3b and Rap 1b:
      interrelation and regulation in physiopathology.
AB  - Platelet Ca2+ signalling involves intracellular Ca2+ pools, whose content is
      controlled by sarco/endoplasmic reticulum Ca2+ATPases (SERCAs). Among these, a
      key role is played by the inositol trisphosphate-sensitive Ca2+ pool, associated
      with the SERCA 3b isoform. We have investigated the control of this Ca2+ pool
      through the cAMP-dependent phosphorylation of the GTP-binding protein, Rap (Ras
      proximate) 1b. We first looked for this Ca2+ pool target of regulation by
      studying the expression of the different SERCA and Rap 1 proteins in human
      platelets and various cell lines, by Western blotting and reverse transcription
      PCR. Since co-expression of Rap 1b and SERCA 3b was obtained, we looked for their
      protein-protein interaction as a function of the cAMP-dependent phosphorylation
      of Rap 1b. Co-immunoprecipitations of SERCA 3b and Rap 1b proteins were found in
      the absence of phosphorylation, induced by the catalytic subunit of the cAMP
      dependent protein kinase (csPKA). In contrast, upon pre-treatment of platelet
      membranes with csPKA, the SERCA 3b dissociated from the Rap 1b protein, in
      agreement with a role of its phosphorylated state in their interaction. Finally,
      we looked for adaptation of this complex in a platelet pathological model of
      hypertension. We investigated the expression of both proteins, as well as the
      cAMP-dependent phosphorylation of Rap 1b and SERCA 3b activity in platelets from
      control normotensive Wistar-Kyoto rats and from spontaneously hypertensive rats
      (SHRs). A decrease in SERCA 3b activity was associated with a decrease in Rap 1b
      endogenous phosphorylation in SHR platelets, consistent with a functional role in
      the regulation of the SERCA 3b-associated Ca2+ pool.

PMID- 9576867
TI  - Enzymic, cysteine-specific ADP-ribosylation in bovine liver mitochondria.
AB  - NAD+ glycohydrolase (NADase) and non-enzymic ADP-ribosylation have been thought
      to be involved in the regulation of mitochondrial Ca2+ fluxes. In this study it
      was found that several conditions (5 mM nicotinamide, 5 mM 3-aminobenzamide, 2 mM
      EDTA, 1 mM ATP, 10 mM dithiothreitol) known to strongly inhibit the NADase
      decreased ADP-ribosylation in bovine liver mitochondrial membranes with [32P]NAD+
      as substrate to only a limited extent, if at all. The reaction led to the
      specific modification of two proteins with apparent molecular masses of approx.
      26 and 53 kDa. An excess of added free ADP-ribose diminished the incorporation of
      label from [32P]NAD+ only slightly. Dithiothreitol inactivated the NADase,
      whereas ADP-ribosylation was unaffected. At low concentrations (25 microM) ADP
      ribosylation was efficient with NAD+, but not ADP-ribose, as substrate. Under
      these conditions mitochondrial ADP-ribosylation seems to occur as an enzymic
      reaction rather than a non-enzymic transfer of ADP-ribose previously liberated
      from NAD+ by NAD+ glycohydrolase. The chemical stability of the protein-ADP
      ribose bonds in the mitochondrial membranes indicated that cysteine residues are
      the predominant acceptors. Moreover, yeast aldehyde dehydrogenase, known to be a
      substrate for thiol-associated ADP-ribosylation, was efficiently ADP-ribosylated
      by using the mitochondrial activity and NAD+ as substrate. The modification of a
      cysteine residue in the aldehyde dehydrogenase was verified by the observation
      that pretreatment of this acceptor protein with N-ethylmaleimide substantially
      decreased its modification. It is therefore concluded that bovine liver
      mitochondria contain a cysteine-specific ADP-ribosyltransferase.

PMID- 9576868
TI  - Nitroarginine and tetrahydrobiopterin binding to the haem domain of neuronal
      nitric oxide synthase using a scintillation proximity assay.
AB  - Nitric oxide synthases (NOS) have a bidomain structure comprised of an N-terminal
      oxygenase domain and a C-terminal reductase domain. The oxygenase domain binds
      haem, (6R)-5,6,7,8-tetrahydro-l-biopterin (tetrahydrobiopterin) and arginine, is
      the site where nitric oxide synthesis takes place and contains determinants for
      dimeric interactions. A novel scintillation proximity assay has been established
      for equilibrium and kinetic measurements of substrate, inhibitor and cofactor
      binding to a recombinant N-terminal haem-binding domain of rat neuronal NOS
      (nNOS). Apparent Kd values for nNOS haem-domain-binding of arginine and Nomega
      nitro-L-arginine (nitroarginine) were measured as 1.6 microM and 25 nM
      respectively. The kinetics of [3H]nitroarginine binding and dissociation yielded
      an association rate constant of 1.3x10(4) s-1.M-1 and a dissociation rate
      constant of 1.2x10(-4) s-1. These values are comparable to literature values
      obtained for full-length nNOS, suggesting that many characteristics of the
      arginine binding site of NOS are conserved in the haem-binding domain.
      Additionally, apparent Kd values were compared and were found to be similar for
      the inhibitors, L-NG-monomethylarginine, S-ethylisothiourea, N-iminoethyl-L
      ornithine, imidazole, 7-nitroindazole and 1400W (N-[3-(aminomethyl) benzyl]
      acetamidine). [3H]Tetrahydrobiopterin bound to the nNOS haem domain with an
      apparent Kd of 20 nM. Binding was inhibited by 7-nitroindazole and stimulated by
      S-ethylisothiourea. The kinetics of interaction with tetrahydrobiopterin were
      complex, showing a triphasic binding process and a single off rate. An
      alternating catalytic site mechanism for NOS is proposed.

PMID- 9576869
TI  - Overexpression and properties of a new thermophilic and thermostable esterase
      from Bacillus acidocaldarius with sequence similarity to hormone-sensitive lipase
      subfamily.
AB  - We previously purified a new esterase from the thermoacidophilic eubacterium
      Bacillus acidocaldarius whose N-terminal sequence corresponds to an open reading
      frame (ORF3) reported to show homology with the mammalian hormone-sensitive
      lipase (HSL)-like group of the esterase/lipase family. To compare the biochemical
      properties of this thermophilic enzyme with those of the homologous mesophilic
      and psychrophilic members of the HSL group, an overexpression system in
      Escherichia coli was established. The protein, expressed in soluble and active
      form at 10 mg/l E. coli culture, was purified to homogeneity and characterized
      biochemically. The enzyme, a 34 kDa monomeric protein, was demonstrated to be a
      B'-type carboxylesterase (EC 3.1.1.1) on the basis of substrate specificity and
      the action of inhibitors. Among the p-nitrophenyl (PNP) esters tested the best
      substrate was PNP-exanoate with Km and kcat values of 11+/-2 microM (mean+/-S.D.,
      n=3) and 6610+/-880 s-1 (mean+/-S.D., n=3) respectively at 70 degreesC and pH7.1.
      In spite of relatively high sequence identity with the mammalian HSLs, the
      psychrophilic Moraxella TA144 lipase 2 and the human liver arylacetamide
      deacetylase, no lipase or amidase activity was detected. A series of substrates
      were tested for enantioselectivity. Substantial enantioselectivity was observed
      only in the resolution of (+/-)-3-bromo-5-(hydroxymethyl)-Delta2-isoxazoline,
      where the (R)-product was obtained with an 84% enantiomeric excess at 36%
      conversion. The enzyme was also able to synthesize acetyl esters when tested in
      vinyl acetate and toluene. Inactivation by diethylpyrocarbonate, diethyl-p
      nitrophenyl phosphate, di-isopropylphosphofluoridate (DFP) and physostigmine, as
      well as labelling with [3H]DFP, supported our previous suggestion of a catalytic
      triad made up of Ser-His-Asp. The activity-stability-temperature relationship is
      discussed in relation to those of the homologous members of the HSL group.

PMID- 9576871
TI  - Enzyme-mediated cytosine deamination by the bacterial methyltransferase M.MspI.
AB  - Most prokaryotic (cytosine-5)-DNA methyltransferases increase the frequency of
      deamination at the cytosine targeted for methylation in vitro in the absence of
      the cofactor S-adenosylmethionine (AdoMet) or the reaction product S
      adenosylhomocysteine (AdoHcy). We show here that, under the same in vitro
      conditions, the prokaryotic methyltransferase, M.MspI (from Moraxella sp.),
      causes very few cytosine deaminations, suggesting a mechanism in which M.MspI may
      avoid enzyme-mediated cytosine deamination. Two analogues of AdoMet, sinefungin
      and 5'-amino-5'-deoxyadenosine, greatly increased the frequency of cytosine
      deamination mediated by M.MspI presumably by introducing a proton-donating amino
      group into the catalytic centre, thus facilitating the formation of an unstable
      enzyme-dihydrocytosine intermediate and hydrolytic deamination. Interestingly,
      two naturally occurring analogues, adenosine and 5'-methylthio-5'-deoxyadenosine,
      which do not contain a proton-donating amino group, also weakly increased the
      deamination frequency by M.MspI, even in the presence of AdoMet or AdoHcy. These
      analogues may trigger a conformational change in the enzyme without completely
      inhibiting the access of solvent water to the catalytic centre, thus allowing
      hydrolytic deamination of the enzyme-dihydrocytosine intermediate. Under normal
      physiological conditions the enzymes M.HpaII (from Haemophilus parainfluenzae),
      M. HhaI (from Haemophilus hemolytica) and M.MspI all increased the in vivo
      deamination frequency at the target cytosines with comparable efficiency.

PMID- 9576872
TI  - Differential expression of selenoproteins by human skin cells and protection by
      selenium from UVB-radiation-induced cell death.
AB  - The generation of reactive oxygen species has been implicated as part of the
      mechanism responsible for UVB-radiation-induced skin damage. In mice, evidence
      suggests that increased dietary selenium intake may protect skin from many of the
      harmful effects of UVB radiation. We sought to determine the selenoprotein
      profile of cultured human skin cells and whether selenium supplementation could
      protect keratinocytes and melanocytes from the lethal effects of UVB radiation.
      Labelling experiments using [75Se]selenite showed qualitative and quantitative
      differences in selenoprotein expression by human fibroblasts, keratinocytes and
      melanocytes. This was most noticeable for thioredoxin reductase (60 kDa) and
      phospholipid glutathione peroxidase (21 kDa); these proteins were identified by
      Western blotting. Despite these differences, we found that a 24 h preincubation
      with sodium selenite or selenomethionine protected both cultured human
      keratinocytes and melanocytes from UVB-induced cell death. With primary
      keratinocytes, the greatest reduction in cell death was found with 10 nM sodium
      selenite (79% cell death reduced to 21.7%; P<0.01) and with 50 nM
      selenomethionine (79% cell death reduced to 13.2%; P<0.01). Protection could be
      obtained with concentrations as low as 1 nM with sodium selenite and 10 nM with
      selenomethionine. When selenium was added after UVB radiation, little protection
      could be achieved, with cell death only being reduced from 88.5% to about 50%
      with both compounds. In all of the experiments sodium selenite was more potent
      than selenomethionine at providing protection from UVB radiation.

PMID- 9576870
TI  - Characterization of the stress-inducing effects of homocysteine.
AB  - The mechanism by which homocysteine causes endothelial cell (EC) injury and/or
      dysfunction is not fully understood. To examine the stress-inducing effects of
      homocysteine on ECs, mRNA differential display and cDNA microarrays were used to
      evaluate changes in gene expression in cultured human umbilical-vein endothelial
      cells (HUVEC) exposed to homocysteine. Here we show that homocysteine increases
      the expression of GRP78 and GADD153, stress-response genes induced by agents or
      conditions that adversely affect the function of the endoplasmic reticulum (ER).
      Induction of GRP78 was specific for homocysteine because other thiol-containing
      amino acids, heat shock or H2O2 did not appreciably increase GRP78 mRNA levels.
      Homocysteine failed to elicit an oxidative stress response in HUVEC because it
      had no effect on the expression of heat shock proteins (HSPs) including HSP70,
      nor did it activate heat shock transcription factor 1. Furthermore homocysteine
      blocked the H2O2-induced expression of HSP70. In support of our findings in
      vitro, steady-state mRNA levels of GRP78, but not HSP70, were elevated in the
      livers of cystathionine beta-synthase-deficient mice with hyperhomocysteinaemia.
      These studies indicate that the activation of stress response genes by
      homocysteine involves reductive stress leading to altered ER function and is in
      contrast with that of most other EC perturbants. The observation that
      homocysteine also decreases the expression of the antioxidant enzymes glutathione
      peroxidase and natural killer-enhancing factor B suggests that homocysteine could
      potentially enhance the cytotoxic effect of agents or conditions known to cause
      oxidative stress.

PMID- 9576873
TI  - The iron ligand sphere geometry of mammalian 15-lipoxygenases.
AB  - We investigated the geometry of the iron ligand sphere of the native rabbit 15
      lipoxygenase (15-LOX) by X-ray absorption spectroscopy using synchrotron
      radiation. The soybean LOX-1 was used as a reference compound because its iron
      ligand sphere is well characterized. For structural information the X-ray
      absorption spectra were evaluated using the Excurve Program (CCLRC Daresbury
      Laboratory, Warrington, U.K.). From the positions of the absorption edges and
      from the intensities of the 1s-3d pre-edge transition peaks a six-coordinate
      ferrous iron was concluded for the rabbit 15-LOX. Evaluation of the extended
      region of the absorption spectra suggested six nitrogen and/or oxygen atoms as
      direct iron ligands, and the following binding distances were determined (means+/
      S.D.; estimated accuracy is +/-0.001nm for bond distances, on the basis of more
      than 22 X-ray absorption spectra): 0.213+/-0.001nm, 0.213+/-0. 001 nm, 0.236+/
      0.001 nm, 0.293+/-0.001 nm, 0.189+/-0.001 nm and 0. 242+/-0.001. Lyophilization
      of the LOX altered the binding distances but did not destroy the octahedral iron
      ligand sphere. For construction of a structural model of the iron ligand sphere
      the binding distances extracted from the X-ray spectra were assigned to specific
      amino acids (His-360, -365, -540, -544 and the C-terminal Ile-662) by molecular
      modelling using the crystal coordinates of the soybean LOX-1 and of a rabbit 15
      LOX-inhibitor complex.

PMID- 9576874
TI  - Mutational analysis of the domain structure of mouse protein phosphatase 2Cbeta.
AB  - The structures of five distinct isoforms of mammalian protein phosphatase 2Cbeta
      (PP2Cbeta-1, -2, -3, -4 and -5) have previously been found to differ only at
      their C-terminal regions. In the present study, we performed mutational analysis
      of recombinant mouse PP2Cbeta-1 to determine the functional domains of the
      molecule and elucidate the biochemical significance of the structural differences
      in the isoforms. Differences in affinity for [32P]phosphohistone but not for
      [32P]phosphocasein were observed among the five PP2Cbeta isoforms. Deletion of 12
      amino acids from the C-terminal end, which form a unique sequence for PP2Cbeta-1,
      caused a 35% loss of activity against [32P]phosphohistone but no loss of activity
      against [32P]phosphocasein. Deletion of up to 78 amino acids from this end did
      not cause any further alteration in activity, whereas deletion of 100 amino acids
      totally eliminated the activity against both [32P]phosphohistone and
      [32P]phosphocasein. On the other hand, deletion of 11 amino acids from the N
      terminal end caused a 97% loss of enzyme activity, and further deletions caused a
      total loss of activity. Substitution of any of the six specific amino acids among
      16 tested in this study, which were located among the 250 N-terminal residues,
      caused 98-100% loss of enzyme activity. Among these amino acids, three (Glu-38, 
      60 and -243) have recently been reported to be essential for the binding of metal
      ions in the catalytic site of the PP2C molecule [Das, Helps, Cohen and Barford
      (1996) EMBO J. 15, 6798-6809]. These observations indicate that PP2Cbeta is
      composed of at least two distinct functional domains, an N-terminal catalytic
      domain of about 310 amino acids and the remaining C-terminal domain, which is
      involved in determination of substrate specificity.

PMID- 9576875
TI  - Biochemical characterization of selenium-containing catalytic antibody as a
      cytosolic glutathione peroxidase mimic.
AB  - A selenium-containing catalytic antibody (Se-4A4), prepared by converting
      reactive serine residues of a monoclonal antibody (4A4) raised against a GSH
      derivative into selenocysteines, acts as a mimic of cytosolic glutathione
      peroxidase (cGPX). To clarify the mechanism of action of this catalytic antibody,
      detailed studies on kinetic behaviour and biological activity were carried out. A
      rate of acceleration (kcat/Km/kuncat) 10(7)-fold that of the uncatalytic reaction
      is observed. Under similar conditions, the turnover number (kcat) of Se-4A4 is
      42% of that of the natural rabbit liver cGPX. The Se-4A4 reaction involves a Ping
      Pong mechanism, which is the same as that of the natural cGPX. The selenocysteine
      residue is located in the binding site of the antibody and is shown to be crucial
      for this activity. Of the thiol compounds tested, only GSH is able to serve as
      substrate for Se-4A4. It was demonstrated, using the free-radical-damage system
      (hypoxanthine/xanthine oxidase) of cardiac mitochondria, that Se-4A4 can protect
      mitochondria from free-radical damage at least 10(4)-fold more effectively than
      the natural cGPX.

PMID- 9576876
TI  - Bile salts stimulate mucin secretion by cultured dog gallbladder epithelial cells
      independent of their detergent effect.
AB  - 1. Bile salts stimulate mucin secretion by the gallbladder epithelium. We have
      investigated whether this stimulatory effect is due to a detergent effect of bile
      salts. 2. The bile salts taurocholic acid (TC) and tauroursodeoxycholic acid
      (TUDC) and the detergents Triton X-100 (12.5-400 microM) and Tween-20 (0.1-3.2
      mM) were applied to monolayers of cultured dog gallbladder epithelial cells.
      Mucin secretion was studied by measuring the secretion of [3H]N-acetyl-d
      glucosamine-labelled glycoproteins. We also attempted to alter the fluidity of
      the apical membrane of the cells through extraction of cholesterol with beta
      cyclodextrin (2.5-15 mM). The effect on TUDC-induced mucin secretion was studied.
      Cell viability was assessed by measuring lactate dehydrogenase (LDH) leakage or
      51Cr release. 3. In contrast with the bile salts, the detergents were not able to
      cause an increase in mucin secretion without causing concomitant cell lysis.
      Concentrations of detergent that increased mucin release (>100 microM Triton X
      100, >0.8 mM Tween-20), caused increased LDH release. Incubation with beta
      cyclodextrin resulted in effective extraction of cholesterol without causing an
      increase in 51Cr release. However, no effect of the presumed altered membrane
      fluidity on TUDC (10 mM)-induced mucin secretion was observed. 4. The stimulatory
      effect of bile salts on mucin secretion by gallbladder epithelial cells is not
      affected by the fluidity of the apical membrane of the cells and also cannot be
      mimicked by other detergents. We conclude that the ability of bile salts to cause
      mucin secretion by the gallbladder epithelium is not determined by their
      detergent properties.

PMID- 9576879
TI  - In vivo muscle force-length behavior during steady-speed hopping in tammar
      wallabies.
AB  - Moderate to large macropodids can increase their speed while hopping with little
      or no increase in energy expenditure. This has been interpreted by some workers
      as resulting from elastic energy savings in their hindlimb tendons. For this to
      occur, the muscle fibers must transmit force to their tendons with little or no
      length change. To test whether this is the case, we made in vivo measurements of
      muscle fiber length change and tendon force in the lateral gastrocnemius (LG) and
      plantaris (PL) muscles of tammar wallabies Macropus eugenii as they hopped at
      different speeds on a treadmill. Muscle fiber length changes were less than +/
      0.5 mm in the plantaris and +/-2.2 mm in the lateral gastrocnemius, representing
      less than 2 % of total fiber length in the plantaris and less than 6 % in the
      lateral gastrocnemius, with respect to resting length. The length changes of the
      plantaris fibers suggest that this occurred by means of elastic extension of
      attached cross-bridges. Much of the length change in the lateral gastrocnemius
      fibers occurred at low force early in the stance phase, with generally isometric
      behavior at higher forces. Fiber length changes did not vary significantly with
      increased hopping speed in either muscle (P>0.05), despite a 1. 6-fold increase
      in muscle-tendon force between speeds of 2.5 and 6.0 m s-1. Length changes of the
      PL fibers were only 7+/-4 % and of the LG fibers 34+/-12 % (mean +/- S.D., N=170)
      of the stretch calculated for their tendons, resulting in little net work by
      either muscle (plantaris 0.01+/-0.03 J; gastrocnemius -0.04+/-0.30 J; mean +/-
      s.d. ). In contrast, elastic strain energy stored in the tendons increased with
      increasing speed and averaged 20-fold greater than the shortening work performed
      by the two muscles. These results show that an increasing amount of strain energy
      stored within the hindlimb tendons is usefully recovered at faster steady hopping
      speeds, without being dissipated by increased stretch of the muscles' fibers.
      This finding supports the view that tendon elastic saving of energy is an
      important mechanism by which this species is able to hop at faster speeds with
      little or no increase in metabolic energy expenditure.

PMID- 9576878
TI  - Isolation of a Chinese hamster fibroblast variant defective in
      dihydroxyacetonephosphate acyltransferase activity and plasmalogen biosynthesis:
      use of a novel two-step selection protocol.
AB  - We have developed a two-step selection protocol to generate a population of
      Chinese hamster ovary (CHO) cell variants that are plasmalogen-deficient, but
      contain intact, functional peroxisomes (plasmalogen-/peroxisome+). This involved
      sequential exposures of a mutagenized cell population to photodynamic damage by
      using two different pyrene-labelled sensors, 9-(1'-pyrene)nonanol and 12-(1'
      pyrene)dodecanoic acid. By this procedure we generated several isolates, all
      except one of which displayed a severe decrease in plasmalogen biosynthesis.
      Further characterization of one of the plasmalogen-deficient isolates, NRel-4,
      showed that it contained intact, functional peroxisomes. Whole-cell homogenates
      from NRel-4 displayed severely decreased dihydroxyacetone phosphate
      acyltransferase, which catalyses the first step in plasmalogen biosynthesis. NRel
      4 and another, recently described, plasmalogen-deficient cell line, NZel-1
      [Nagan, Hajra, Das, Moser, Moser, Lazarow, Purdue and Zoeller (1997) Proc. Natl.
      Acad. Sci. U.S. A. 94, 4475-4480] were hypersensitive to singlet oxygen,
      supporting the notion of plasmalogens as radical oxygen scavengers. Wild-type
      like resistance could be conferred on NRel-4 upon restoration of plasmalogen
      content by supplementation with a bypass compound, sn-1-hexadecylglycerol. NRel-4
      and other plasmalogen-/peroxisome+ strains will allow us to examine further the
      role of ether lipids in cellular functions without complications associated with
      peroxisome deficiency, and might serve as an animal cell model for certain forms
      of the human genetic disorder rhizomelic chondrodysplasia punctata.

PMID- 9576877
TI  - Agonist-specific alterations in receptor-phospholipase coupling following
      inactivation of Gi2alpha gene.
AB  - Different forms of phospholipase A2, together with pertussis toxin-sensitive G
      proteins, [Ca2+]i (intracellular Ca2+ concentration), protein kinase C,
      calmodulin, protein tyrosine kinases, mitogen-activated protein kinases and
      Ca2+/calmodulin-dependent protein kinase appear to play a role in agonist
      mediated release of arachidonic acid. Here we report that fibroblasts from 14-day
      old mouse embryos with inactivated Gi2alpha (alpha-subunit of the heterotrimeric
      G-protein Gi2) gene display a marked decrease in the ability of lysophosphatidic
      acid, thrombin and Ca2+ ionophores to release arachidonic acid compared with
      their normal counterparts. The requirement for Gi2alpha in the release of
      arachidonic acid following increased [Ca2+]i may be explained by the incomplete
      translocation of cytosolic phospholipase A2 observed in Gi2alpha-deficient cells.
      Paradoxically, inactivation of the Gi2alpha gene resulted in up-regulation of
      bradykinin receptors and their coupling to increased arachidonic acid release,
      phospholipase C activity and [Ca2+]i. A concomitant increase in basal
      phospholipase C activity was also observed in the Gi2alpha-deficient cells. These
      observations establish a pleiotropic and essential role for Gi2alpha in receptor
      phospholipase coupling that contrasts with its less obligatory participation in
      agonist-mediated inhibition of adenylate cyclase.

PMID- 9576880
TI  - Ca2+ signaling in fowl aortic smooth muscle increases during maturation but is
      impaired in neointimal plaques.
AB  - Many bird species show the spontaneous development of high arterial pressure and
      vascular lesions in the aorta and other large arteries. In chickens, arterial
      pressure tends to increase with age/maturation (particularly in males), and
      subendothelial hyperplasia (neointima) in the abdominal aorta is often seen prior
      to sexual maturation. The mechanisms involved, however, are not known. Our aim,
      therefore, was to determine (1) whether cytosolic Ca2+ signaling (CCS) responses
      to vasoactive substances in fowl aortic smooth muscle differ among chickens at
      different maturation stages and (2) whether CCS responses to Ca2+ channel
      agonists in neointimal plaques differ from those in normal aortic smooth muscle.
      K+ increased CCS in a dose-dependent manner in isolated and superfused abdominal
      aortic smooth muscle tissue from chicks (5-9 weeks old), pullets (11-18 weeks
      old) and adult hens (20 weeks and older); CCS responses increased as chickens
      matured. The addition of Bay K 8644 (10(-6)mol l-1) to Ringer's solution
      containing 50 mmol l-1 K+ further increased CCS, and this response was reduced to
      half by nifedipine (10(-6)mol l-1). Norepinephrine did not alter CCS in chicks,
      whereas marked dose-dependent increases in CCS were noted in pullets. In contrast
      to the CCS responses to K+, the norepinephrine-induced CCS responses became
      smaller in adult hens. Isolated neointimal plaques showed only slight increases
      in CCS in response to 50 mmol l-1 K+ plus Bay K 8644, whereas clear responses
      were noted in aortic smooth muscle tissue underlying the plaques. These results
      suggest (1) that CCS responses to Ca2+ channel agonists increased with sexual
      maturation in fowl, but (2) that CCS responses to norepinephrine were low in
      mature hens and to K+ plus Bay K 8644 were low in spontaneously developed
      neointima, suggesting that phenotypic modulation of Ca2+ channel/norepinephrine
      receptors may have occurred during maturation/aging and in neointima.

PMID- 9576881
TI  - Scavenger-receptor-mediated endocytosis in endocardial endothelial cells of
      Atlantic cod Gadus morhua.
AB  - Scavenger receptors are multifunctional integral membrane proteins that mediate
      the endocytosis of many different macromolecular polyanions and also participate
      in host defence reactions and cell adherance. In Atlantic cod (Gadus morhua L.),
      two intravenously injected scavenger receptor ligands, [125I]tyramine-cellobiose
      labelled formaldehyde-treated serum albumin (125I-TC-FSA) and 125I-labelled N
      terminal propeptide of type I procollagen (125I-PINP), distributed mainly to the
      heart. Cellular uptake was visualized by injections of fluorescently labelled FSA
      (FITC-FSA), which was recovered in discrete vesicles in endocardial endothelial
      cells of both heart chambers. Studies in vitro showed that radioiodinated FSA and
      PINP were endocytosed and degraded very efficiently by cultured atrial
      endocardial endothelial cells. Moreover, uptake of 125I-FSA was Ca2+-independent.
      Out of a range of unlabelled ligands, only the scavenger receptor ligands FITC
      FSA, polyinosinic acid and, to a varying extent, FSA, acetylated low-density
      lipoprotein (AcLDL) and PINP, were able to compete with radioiodinated FSA, PINP
      or AcLDL for uptake in isolated endocardial cells. From our findings, we conclude
      that the endocardial endothelial cells are major carriers of scavenger receptors
      in cod. In addition, our results strengthen the hypothesis that these cells in
      cod play the same important function as that established for the scavenger
      endothelial cells of the mammalian liver.

PMID- 9576882
TI  - Arousal shifts in quiescent locusts 
AB  - Locusts are usually quiescent at night, but this state can be interrupted by
      spontaneous periods of motor activity, or arousals, that can also be induced by
      exposure to light stimuli. To investigate whether repeated arousing stimulation
      has any lasting effect on behaviour, locusts were confronted at night with a
      series of 1 s light stimuli. Groups of three stimuli at intervals of 60 s were
      repeated 11 times at 10 min intervals during the first experimental night, and
      three stimuli at intervals of 90 s were repeated at 15 min intervals during the
      next night. Arousals and the effects of stimulation were monitored as changes in
      the spike activity of muscles in the basal part (the scapus) of the right
      antenna. In the early part of the night preceding the presentation of the light
      stimuli, neither 60 s nor 90 s periods were present as significant peaks in
      spontaneous changes in spike activity. The initial stimulus of a series evoked an
      arousal response that habituated on repetition of the stimulus. The end of the
      series of stimuli was followed by changes in spike activity that tended to have
      the same periodicity as the preceding stimuli. Furthermore, a single light
      stimulus at the end of the night evoked changes in spike activity that again
      tended to have the same periodicity as the preceding entraining stimuli. Repeated
      stimulation may therefore establish a memory trace for the period of stimulation
      that can be recalled either spontaneously or by the application of an appropriate
      external stimulus.

PMID- 9576884
TI  - Oxygen-sensitive flight metabolism in the dragonfly erythemis simplicicollis 
AB  - Insect flight metabolism is completely aerobic, and insect resting metabolism is
      quite insensitive to atmospheric oxygen level, suggesting a large safety margin
      in the capacity of the tracheal system to deliver oxygen during flight. We tested
      the sensitivity of flight initiation and metabolism to atmospheric oxygen level
      in the libellulid dragonfly Erythemis (Mesothemis) simplicicollis using flow
      through respirometric measurements of the rate of CO2 emission (<IMG
      src="/images/symbols/v_dot.gif" WIDTH="9" HEIGHT="14" ALIGN="BOTTOM"
      NATURALSIZEFLAG="3">CO2). Flight initiations were unimpaired in atmospheric
      oxygen levels as low as 10 %. However, flight metabolic rate was affected by
      ambient oxygen level. Flight <IMG src="/images/symbols/v_dot.gif" WIDTH="9"
      HEIGHT="14" ALIGN="BOTTOM" NATURALSIZEFLAG= "3">CO2 decreased in hypoxic mixtures
      (5 kPa or 10 kPa oxygen) and increased in hyperoxic atmospheres (30 kPa or 50 kPa
      oxygen), suggesting that ambient oxygen level influences flight muscle oxygen
      partial pressure (PO2) and the vigour of flight. These are the first data to show
      oxygen-limitation of flight metabolism in a free-flying insect. A low safety
      margin for oxygen delivery during dragonfly flight is consistent with a previous
      hypothesis that atmospheric hyperoxia facilitated gigantism in Paleozoic
      protodonates. However, allometric studies of tracheal morphology, and mechanisms
      and capacity of gas exchange in extant insects are necessary in order to test the
      hypothesis that the oxygen-sensitivity of aerobic metabolism increases with body
      size in insects.

PMID- 9576883
TI  - Neither respiration nor cytochrome c oxidase affects mitochondrial morphology in
      Saccharomyces cerevisiae.
AB  - Previous studies have reported that mitochondrial morphology and volume in yeast
      cells are linked to cellular respiratory capacity. These studies revealed that
      mitochondrial morphology in glucose-repressed or anaerobically grown cells, which
      lack or have reduced levels of respiration, is different from that in fully
      respiring cells. Although both oxygen deprivation and glucose repression decrease
      the levels of respiratory chain proteins, they decrease the expression of many
      non-mitochondrial proteins as well, making it difficult to determine whether it
      is a defect in respiration or something else that effects mitochondrial
      morphology. To determine whether mitochondrial morphology is dependent on
      respiration per se, we used a strain with a null mutation in PET100, a nuclear
      gene that is specifically required for the assembly of cytochrome c oxidase.
      Although this strain lacks respiration, the mitochondrial morphology and volumes
      are both comparable to those found in its respiration-proficient parent. These
      findings indicate that respiration is not involved in the establishment or
      maintenance of yeast mitochondrial morphology, and that the previously observed
      effects of oxygen availability and glucose repression on mitochondrial morphology
      are not exerted through the respiratory chain. By applying the principle of
      symmorphosis to these findings, we conclude that the shape and size of the
      mitochondrial reticulum found in respiring yeast cells is maintained for reasons
      other than respiration.

PMID- 9576885
TI  - Development of sensory processes during limb regeneration in adult crayfish.
AB  - The capacity of the crayfish Procambarus clarkii to regenerate its walking legs
      provides a system for studying the mechanisms of neural regeneration and repair.
      A set number of excitatory and inhibitory motor neurons innervate all the limb
      musculature throughout the normal development and regeneration of a limb. The
      cell bodies of the motor neurons reside within the segmental ganglion and, upon
      loss of the limb, their axons regrow from their severed distal ends. The cell
      bodies of the sensory neurons, in contrast, are located close to their sensory
      endings within the limb, and they are therefore lost, along with the limb, upon
      autotomy, leaving the severed, distal axonal stumps of the sensory neurons within
      the ganglionic root. During the regeneration of a limb, new sensory neurons
      develop within the limb, and their axons must then grow into the ganglionic root
      to make the appropriate connections for the new limb to become functional.
      Evidence is presented in the present paper that the sensory axonal stumps do not
      degenerate before the new sensory neurons appear within the root as the limb
      regenerates. These results also indicate a progressive advance of growth cones,
      presumably sensory in origin, towards the neuropil within the ganglion over time.

PMID- 9576887
TI  - Partitioning of oxygen uptake between the gills and skin in fish larvae: a novel
      method for estimating cutaneous oxygen uptake.
AB  - The goal of this study was to develop an alternative to the traditional rubber
      dam method for measuring cutaneous oxygen uptake in bimodally respiring (skin +
      gills) fish larvae. The method tested involved using microelectrodes to measure
      the PO2 gradient in the diffusive boundary layer adjacent to seven positions on
      the skin surface (one on the head, two on the yolk sac, two on the trunk, one at
      the base of the dorsal fin-fold and one on the proximal portion of the caudal fin
      fold) of rainbow trout (Oncorhynchus mykiss) larvae in still water. The PO2
      gradient (deltaPO2/delta x, where x is the distance from the skin surface) was
      then used to calculate area-specific rate of O2 uptake (.MO2/A) according to the
      Fick equation, .MO2/A=Dbeta(deltaPO2/deltax), where A is the cross-sectional area
      of the boundary layer, D is the diffusion coefficient and beta is the capacitance
      coefficient for O2 in water. The accuracy of the method was assessed by comparing
      it with the rubber dam method. After correcting for differences in body mass, the
      two methods gave essentially identical results. According to the boundary layer
      method, the mean (+/-95 % CI) rate of O2 uptake across the skin of newly hatched
      rainbow trout at 10 degrees C is 3.13+/-0.18 microg O2 cm-2h-1 (N=265). The
      corresponding value obtained using the rubber dam method was 3. 36+/-0.35 microg
      O2 cm-2 h-1 (N=27). The advantages of the boundary layer method are that it can
      be used with smaller, more delicate larvae and that variables, such as flow rate,
      that can affect the efficiency of gas exchange can be regulated more precisely.
      The boundary layer method also permits examination of regional differences in
      exchange efficiency, although in still water such differences do not appear to be
      significant in trout larvae. The mean steepness of the PO2 gradient in the
      boundary layer and, hence, the mean rate of area-specific O2 uptake were
      essentially the same (P>0.05) at all seven locations tested in this study. The
      boundary layer method can potentially be used to study the transcutaneous flux,
      not only of O2 but of virtually any diffusible substance that can be measured
      with microelectrodes and that is consumed (e.g. Na+, Ca2+) or excreted (e.g. CO2,
      NH3) by fish larvae or other small organisms.

PMID- 9576886
TI  - The concentration-dependence of CRF-like diuretic peptide: mechanisms of action.
AB  - The mechanism of action of synthetic CCRF-DP, the corticotropin-releasing factor
      (CRF)-related diuretic peptide of the salt marsh mosquito Culex salinarius, was
      investigated in isolated Malpighian tubules of the yellow fever mosquito Aedes
      aegypti. A low concentration of CCRF-DP (10(-9)mol l-1) caused a small but
      insignificant increase in transepithelial secretion of NaCl and fluid, but
      significantly reduced transepithelial voltage and resistance without a change in
      short-circuit current, pointing to the stimulation of passive Cl- transport
      through the paracellular pathway as the principal mechanism of a mild diuresis.
      Significant changes in voltage and resistance but not in short-circuit current
      were duplicated by the ionophore A23187 (0.4 micromol l-1), suggesting Ca2+ as a
      second messenger at 10(-9)mol l-1 CCRF-DP. A high concentration of CCRF-DP (10(
      7)mol l-1) significantly increased transepithelial secretion of NaCl and fluid
      and significantly increased short-circuit current, pointing to the stimulation of
      active Na+ transport through the transcellular pathway as the mechanism of a
      strong diuresis. This effect was mimicked by dibutyryl-cAMP, suggesting cAMP as a
      second messenger at 10(-7)mol l-1 CCRF-DP. Dibutyryl-cGMP had no effects. These
      results suggest dose-dependent, receptor-mediated effects of CCRF-DP that target
      discrete transport pathways via discrete second messengers: low concentrations of
      CCRF-DP cause a mild diuresis, apparently via Ca2+-mediated effects on
      paracellular Cl- transport, and high concentrations cause a strong diuresis via
      cAMP-mediated effects on active transcellular Na+ transport in addition to the
      effects on the paracellular pathway.

PMID- 9576888
TI  - Tail-flip mechanism and size-dependent kinematics of escape swimming in the brown
      shrimp crangon crangon 
AB  - Tail-flip escape swimming by the brown shrimp Crangon crangon has been
      investigated across a range of body lengths (11-69 mm) using high-speed video
      analysis. This has revealed several novel aspects of the tail-flip mechanism when
      compared with that of other decapod crustaceans that have been studied. (i) The
      pattern of body flexion in C. crangon produces movement of the cephalothorax as
      well as the abdomen about the centre of mass. (ii) Shrimps form a 'head-fan' with
      their antennal scales, in addition to the tail-fan formed by their uropods,
      apparently for generating thrust during tail-flips. (iii) Shrimps typically swim
      on their side rather than in an upright body position. It is suggested that these
      features may be interlinked and derive from habitat specialisation. The kinematic
      properties of tail-flips were found to vary with shrimp size. As shrimp body
      length increased, the rate of body flexion and re-extension decreased whilst the
      duration of tail-flips increased. Mean (and maximum) velocity estimates ranged
      between 0.4 m s-1 (0.7 m s-1) and 1.1 m s-1 (1.8 m s-1) for shrimps of different
      sizes. The combined effects of escape behaviour and size-dependent variability in
      tail-flip kinematics will have important implications with regard to predation
      risk.

PMID- 9576889
TI  - The role of the frontal ganglion in the feeding and eclosion behavior of the moth
      manduca sexta 
AB  - We have examined the musculature and motor patterns of the foregut and the role
      of the frontal ganglion in the adult moth Manduca sexta. During adult
      development, the structure of the foregut changes from a simple straight tube to
      a pump consisting of a flexible-roofed chamber or cibarium, with dilator muscles
      that raise the roof to draw in fluids and a compressor to push it down and force
      the fluid down the thin-walled esophagus. The frontal ganglion drives the
      activity of this cibarial pump during feeding, which is triggered by the
      application of sucrose solution or water to the proboscis. The feeding motor
      pattern consists of coupled bursts of the pump dilators and shorter-duration,
      high-frequency bursts of spikes from the pump compressor. The pump is also
      activated at the adult molt. At this time, it is used both before the moth
      emerges from the pupal case for swallowing molting fluid and again after
      emergence for swallowing air. These behaviors are important for eclosion and are
      necessary for the expansion of the wings after eclosion. Their motor patterns are
      similar to the feeding program. Up to 24 h before adult ecdysis, this motor
      pattern can be triggered by the peptide eclosion hormone. The other eclosion
      related peptide, Manduca sexta eclosion-triggering hormone, does not appear to
      trigger activity of the cibarial pump.

PMID- 9576890
TI  - Natriuretic peptide binding sites in the gills of the pouched lamprey Geotria
      australis.
AB  - Iodinated atrial natriuretic peptide (ANP) binding sites were examined in the
      gills and ventral aorta of the adult upstream-migrating lamprey Geotria australis
      using tissue section autoradiography, in vitro competition analysis and affinity
      cross-linking, while guanylate cyclase assays were performed on gill membranes of
      both adult and juvenile lampreys. A partial natriuretic peptide (NP) receptor
      sequence was amplified using reverse transcription/polymerase chain reaction (RT
      PCR). The results indicated that there was specific NP binding to the aortic
      endothelium and to pillar cell regions in the axial plate and secondary lamellae.
      In competition studies, 50 % of NP binding was abolished by 4 nmol l-1 rat ANP,
      35 nmol l-1 porcine C-type NP (CNP) and 45 nmol l-1 C-ANF (a truncated ANP).
      Affinity cross-linking followed by SDS-PAGE demonstrated two binding sites at 205
      and 65 kDa under non-reducing conditions and at 85 and 65 kDa under reducing
      conditions. Guanylate cyclase assays demonstrated that, while no NP-stimulated GC
      activity occurred in adult lampreys, NP-stimulated enhancement of cyclic GMP
      accumulation was found in juveniles in fresh water and more particularly in salt
      water. RT-PCR amplified a 471 base pair fragment with 68 % amino acid sequence
      homology to the eel natriuretic peptide receptor D (NPR-D). This study suggests
      that NP binding sites in the adult gill and aorta are of an NPR-C/D type, whereas
      an additional GC-coupled site exists in juveniles.

PMID- 9576891
TI  - Covariation in regulation of affinity for branchial zinc and calcium uptake in
      freshwater rainbow trout.
AB  - The possible coupling between regulation of the affinities for branchial Zn and
      Ca influx was investigated in juvenile rainbow trout Oncorhynchus mykiss
      acclimated to relatively hard fresh water ([Ca]=1.0 mmol l-1). The Km for
      branchial Ca influx was manipulated experimentally by exposing the fish to 2.3
      micromol l-1 waterborne Zn for a total of 28 days. This procedure resulted in
      rapidly increased Km values for both Ca and Zn influx, an effect that remained
      through the experimental period. There was a significant linear correlation
      (r=0.88, P<0.02) between Km values for Ca and Zn measured at the same time
      points. Zn exposure caused progressively increasing maximum rate of transport,
      Jmax, values for Zn relative to the control value, but there was little, if any,
      effect on Jmax for Ca. These results support the idea of a shared transport site
      for Zn and Ca at the apical membrane of the gill epithelium and suggest that
      there is a certain degree of coregulation of branchial Zn and Ca uptake in
      rainbow trout. Removal of Ca from the water resulted in a large (six- to 24-fold)
      increase in affinity (decreased Km) for Zn influx and a modest (1.1- to 1.8-fold)
      increase in Jmax for Zn. Thus, Ca is a competitive inhibitor of Zn influx. In
      water lacking Ca, the Km for Zn in Zn-acclimated fish was no different from that
      of the control fish, suggesting that the Ca2+/Zn2+ transporter was regulated to
      improve Ca uptake.

PMID- 9576892
TI  - Confocal laser scanning and electron microscopical studies on osmoregulatory
      epithelia in the branchial cavity of the lobster homarus gammarus 
AB  - The adult lobster Homarus gammarus is a weak hyper-regulator at low salinity. The
      objective of this study was to locate the ion-transporting tissues in the
      branchial chamber of this species, using electron microscopy and confocal laser
      scanning microscopy with a fluorescent vital stain for mitochondria, DASPMI,
      which is widely used to locate mitochondria-rich cells in ion-transporting
      epithelia of fish. A thick mitochondria-rich epithelium is present on the inner
      side of the branchiostegite and over the entire surface of the epipodites.
      Ultrastructural observations confirm that this tissue has features typical of an
      ion-transporting epithelium. When the lobster is transferred to low salinity,
      these epithelia undergo marked ultrastructural changes, such as an increase in
      thickness related to the development of basolateral infoldings, the appearance of
      numerous vesicles and an increase in height of the apical microvilli. In the
      gills, the branchial filaments are lined by a thin and poorly differentiated
      epithelium, containing numerous mitochondria; no significant ultrastructural
      changes were observed in the gills of animals acclimated to low salinity. In
      summary, in H. gammarus, no evidence of osmoregulatory structures was found in
      the gills. Differentiated ion-transporting epithelia are present in the branchial
      cavity, on the inner side of the branchiostegite and on the epipodites; these
      organs are probably involved in osmoregulation.

PMID- 9576893
TI  - Long-term adaptation of Ca2+-dependent behaviour in Paramecium tetraurelia.
AB  - Prolonged exposure to KCl has long been recognized to modify swimming behaviour
      in Paramecium tetraurelia, a phenomenon known as 'adaptation'. In this study, we
      have investigated behavioural adaptation systematically. A 24 h exposure to 30
      mmol l-1 KCl deprived cells of the ability to respond behaviourally to two
      established chemoeffectors. We also explored the effects of 30 mmol l-1 KCl on
      the duration of backward swimming induced by Ba2+ and Mg2+. A brief (60 min)
      exposure prevented cells from swimming backwards in response to either cation,
      but recovery was rapid (<60 min) following a return to control medium. Prolonged
      (48 h) exposure caused a more persistent loss of response to Ba2+, so that
      several hours was now required for recovery. Surprisingly, responses to Mg2+
      reappeared during 6-8 h in KCl, with backward swimming durations increasing to
      more than 300 % of control values after 26 h. Thus, we can distinguish two phases
      to adaptation. The short-term phase is characterized by an inability to respond
      behaviourally to most stimuli and might be adequately explained in terms of Ca2+
      channel inactivation and K+-induced shifts in membrane potential. The long-term
      phase is characterized by enhanced responses to Mg2+ (and also to Na+),
      suggesting that a more extensive reprogramming of membrane excitability may occur
      during chronic K+-induced depolarization.

PMID- 9576894
TI  - The energetic cost of copulation in a polygynandrous millipede 
AB  - We determined the energetic cost of copulation in both sexes of Alloporus
      uncinatus, a polygynandrous millipede in which copulation can last for several
      hours and involves physical restraint of the female by the male. We found an
      elevation in the rate of oxygen consumption by males and a depression in the rate
      of oxygen consumption by females during copulation. The rate of oxygen
      consumption of females, but not of males, was elevated immediately after
      copulation, indicating that females had built up and were repaying an oxygen
      debt. On this basis, we estimated energy expenditure during copulation to be 30 %
      above resting levels in males and 14 % above resting levels in females. As
      matings are frequent in this species in the wild throughout the 4 month breeding
      season, we suggest that the energetic demands of copulation are a previously
      overlooked potentially significant cost of reproduction in this species and in
      other invertebrate species with similar mating patterns.

PMID- 9576895
TI  - Artificial death switches: induction of apoptosis by chemically induced caspase
      multimerization.

PMID- 9576896
TI  - An introduction to "A song among the ruins".

PMID- 9576897
TI  - Greetings: 50 years of Atomic Bomb Casualty Commission-Radiation Effects Research
      Foundation studies.
AB  - The Atomic Bomb Casualty Commission was established in Hiroshima in 1947 and in
      Nagasaki in 1948 under the auspices of the U.S. National Academy of Sciences to
      initiate a long-term and comprehensive epidemiological and genetic study of the
      atomic bomb survivors. It was replaced in 1975 by the Radiation Effects Research
      Foundation which is a nonprofit Japanese foundation binationally managed and
      supported with equal funding by the governments of Japan and the United States.
      Thanks to the cooperation of the survivors and the contributions of a multitude
      of scientists, these studies flourish to this day in what must be the most
      successful long-term research collaboration between the two countries. Although
      these studies are necessarily limited to the effects of acute, whole-body, mixed
      gamma-neutron radiation from the atom bombs, their comprehensiveness and duration
      make them the most definitive descriptions of the late effects of radiation in
      humans. For this reason, the entire world relies heavily on these data to set
      radiation standards. As vital as the study results are, they still represent
      primarily the effects of radiation on older survivors. Another decade or two
      should correct this deficiency and allow us to measure definitively the human
      risk of heritable mutation from radiation. We look to the worldwide radiation and
      risk community as well as to the survivors who have contributed so much to what
      has been done already to accomplish this goal.

PMID- 9576898
TI  - The Atomic Bomb Casualty Commission in retrospect.
AB  - For 50 years, the Atomic Bomb Casualty Commission (ABCC) and its successor, the
      Radiation Effects Research Foundation (RERF), have conducted epidemiological and
      genetic studies of the survivors of the atomic bombs and of their children. This
      research program has provided the primary basis for radiation health standards.
      Both ABCC (1947-1975) and RERF (1975 to date) have been a joint enterprise of the
      United States (through the National Academy of Sciences) and of Japan. ABCC began
      in devastated, occupied Japan. Its mission had to be defined and refined. Early
      research revealed the urgent need for long term study. In 1946, a Directive of
      President Truman enjoined the National Research Council of the National Academy
      of Sciences to develop the program. By 1950, ABCC staff exceeded 1,000, and
      clinical and genetic studies were underway. Budgetary difficulties and other
      problems almost forced closure in 1953. In 1955, the Francis Report led to a
      unified epidemiological study. Much progress was made in the next decade, but
      changing times required founding of a binational nonprofit organization (RERF)
      with equal participation by Japan and the United States. New programs have been
      developed and existing ones have been extended in what is the longest continuing
      health survey ever undertaken.

PMID- 9576899
TI  - Genetic studies at the Atomic Bomb Casualty Commission-Radiation Effects Research
      Foundation: 1946-1997.

PMID- 9576900
TI  - The somatic effects of exposure to atomic radiation: the Japanese experience,
      1947-1997.

PMID- 9576901
TI  - Trends in odor intensity for human and electronic noses: relative roles of
      odorant vapor pressure vs. molecularly specific odorant binding.
AB  - Response data were collected for a carbon black-polymer composite electronic nose
      array during exposure to homologous series of alkanes and alcohols. The mean
      response intensity of the electronic nose detectors and the response intensity of
      the most strongly driven set of electronic nose detectors were essentially
      constant for members of a chemically homologous odorant series when the
      concentration of each odorant in the gas phase was maintained at a constant
      fraction of the odorant's vapor pressure. A similar trend is observed in human
      odor detection threshold values for these same homologous series of odorants.
      Because the thermodynamic activity of an odorant at equilibrium in a sorbent
      phase is equal to the partial pressure of the odorant in the gas phase divided by
      the vapor pressure of the odorant and because the activity coefficients are
      similar within these homologous series of odorants for sorption of the vapors
      into specific polymer films, the data imply that the trends in detector response
      can be understood based on the thermodynamic tendency to establish a relatively
      constant concentration of sorbed odorant into each of the polymeric films of the
      electronic nose at a constant fraction of the odorant's vapor pressure.
      Similarly, the data are consistent with the hypothesis that the odor detection
      thresholds observed in human psychophysical experiments for the odorants studied
      herein are driven predominantly by the similarity in odorant concentrations
      sorbed into the olfactory epithelium at a constant fraction of the odorant's
      vapor pressure.

PMID- 9576902
TI  - Locomotion: dealing with friction.
AB  - To move on land, in water, or in the air, even at constant speed and at the same
      level, always requires an expenditure of energy. The resistance to motion that
      has to be overcome is of many different kinds depending on size, speed, and the
      characteristics of the medium, and is a fascinating subject in itself. Even more
      interesting are nature's stratagems and solutions toward minimizing the effort
      involved in the locomotion of different types of living creatures, and humans'
      imitations and inventions in an attempt to do at least as well.

PMID- 9576903
TI  - Application of a time-dependent coalescence process for inferring the history of
      population size changes from DNA sequence data.
AB  - Distribution of pairwise differences of nucleotides from data on a sample of DNA
      sequences from a given segment of the genome has been used in the past to draw
      inferences about the past history of population size changes. However, all
      earlier methods assume a given model of population size changes (such as sudden
      expansion), parameters of which (e.g., time and amplitude of expansion) are
      fitted to the observed distributions of nucleotide differences among pairwise
      comparisons of all DNA sequences in the sample. Our theory indicates that for any
      time-dependent population size, N(tau) (in which time tau is counted backward
      from present), a time-dependent coalescence process yields the distribution,
      p(tau), of the time of coalescence between two DNA sequences randomly drawn from
      the population. Prediction of p(tau) and N(tau) requires the use of a reverse
      Laplace transform known to be unstable. Nevertheless, simulated data obtained
      from three models of monotone population change (stepwise, exponential, and
      logistic) indicate that the pattern of a past population size change leaves its
      signature on the pattern of DNA polymorphism. Application of the theory to the
      published mtDNA sequences indicates that the current mtDNA sequence variation is
      not inconsistent with a logistic growth of the human population.

PMID- 9576904
TI  - DNA ligands that bind tightly and selectively to cellobiose.
AB  - Cell surface oligosaccharides have been shown to play essential biological roles
      in such diverse biological phenomena as cellular adhesion, molecular recognition,
      and inflammatory response. The development of high-affinity ligands capable of
      selectively recognizing a variety of small motifs in different oligosaccharides
      would be of significant interest as experimental and diagnostic tools. As a step
      toward this goal we have developed DNA ligands that recognize the disaccharide
      cellobiose, whether in soluble form or as the repeating unit of the polymer,
      cellulose. These DNA "aptamers" bind with high selectivity to cellobiose with
      little or no affinity for the related disaccharides lactose, maltose, and
      gentiobiose. Thus, the DNA ligands can discriminate sugar epimers, anomers, and
      disaccharide linkages.

PMID- 9576905
TI  - The chromatin unfolding domain of chromosomal protein HMG-14 targets the N
      terminal tail of histone H3 in nucleosomes.
AB  - Nonhistone chromosomal protein HMG-14 is a nucleosomal binding protein that
      unfolds the higher-order chromatin structure and enhances the transcriptional
      potential of chromatin, but not that of DNA. Both the transcriptional enhancement
      and the chromatin unfolding activities of HMG-14 are mediated through the C
      terminal region of the protein. Here we study the molecular interactions of both
      this region and the N-terminal region of HMG-14 with nucleosome cores. By protein
      photocrosslinking we demonstrate that the N-terminal domain of HMG-14 targets a
      restricted region in histone H2B, whereas the C-terminal chromatin unfolding
      domain of HMG-14 targets a restricted region in the N terminus of histone H3. The
      N-terminal regions of the core histones are involved in the folding of
      oligonucleosomes and are the target of various activities associated with
      chromatin unfolding and transcriptional activation. We suggest that specific
      interactions between the C-terminal domain of HMG-14 and the N-terminal tail of
      histone H3 reduce the compaction of chromatin. These findings provide insights
      into the molecular mechanism whereby HMG-14/-17 proteins reduce the repressive
      effect of chromatin, and they also broaden the scope of the molecular
      interactions involving the N termini of the core histones in nucleosomes.

PMID- 9576906
TI  - The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active
      complexes with circadian and hypoxia factors.
AB  - We report that MOP3 is a general dimerization partner for a subset of the basic
      helix-loop-helix (bHLH)-PER-ARNT-SIM (PAS) superfamily of transcriptional
      regulators. We demonstrated that MOP3 interacts with MOP4, CLOCK, hypoxia
      inducible factor 1alpha (HIF1alpha), and HIF2alpha. A DNA selection protocol
      revealed that the MOP3-MOP4 heterodimer bound a CACGTGA-containing DNA element.
      Transient transfection experiments demonstrated that the MOP3-MOP4 and MOP3-CLOCK
      complexes bound this element in COS-1 cells and drove transcription from a linked
      luciferase reporter gene. We also deduced the high-affinity DNA binding sites for
      MOP3-HIF1alpha complex (TACGTGA) and used transient transfection experiments to
      demonstrate that the MOP3-HIF1alpha and MOP3-HIF2alpha heterodimers bound this
      element, drove transcription, and responded to cellular hypoxia. Finally, we
      found that MOP3 mRNA expression overlaps in a number of tissues with each of its
      four potential partner molecules in vivo.

PMID- 9576907
TI  - Association-induced folding of globular proteins.
AB  - It has generally been assumed that the aggregation of partially folded
      intermediates during protein refolding results in the termination of further
      protein folding. We show here, however, that under some conditions the
      association of partially folded intermediates can induce additional structure
      leading to soluble aggregates with many native-like properties. The amount of
      secondary structure in a monomeric, partially folded intermediate of
      staphylococcal nuclease was found to double on formation of soluble aggregates at
      high protein or salt concentrations. In addition, more globularity, as determined
      from Kratky plots of small-angle x-ray scattering data, was also noted in the
      associated states.

PMID- 9576908
TI  - Genetic, biochemical, and crystallographic characterization of Fhit-substrate
      complexes as the active signaling form of Fhit.
AB  - Alterations in the FHIT gene at 3p14.2 occur as early and frequent events in the
      development of several common human cancers. The ability of human Fhit-negative
      cells to form tumors in nude mice is suppressed by stable reexpression of Fhit
      protein. Fhit protein is a diadenosine P1,P3-triphosphate (ApppA) hydrolase whose
      fungal and animal homologs form a branch of the histidine triad (HIT) superfamily
      of nucleotide-binding proteins. Because the His-96 --> Asn substitution of Fhit,
      which retards ApppA hydrolase activity by seven orders of magnitude, did not
      block tumor-suppressor activity in vivo, we determined whether this mutation
      affected ApppA binding or particular steps in the ApppA catalytic cycle. Evidence
      is presented that His-96 --> Asn protein binds ApppA well and forms an enzyme-AMP
      intermediate extremely poorly, suggesting that Fhit-substrate complexes are the
      likely signaling form of the enzyme. The cocrystal structure of Fhit bound to Ado
      p-CH2-p-ps-Ado (IB2), a nonhydrolyzable ApppA analog, was refined to 3.1 A, and
      the structure of His-96 --> Asn Fhit with IB2 was refined to 2.6 A, revealing
      that two ApppA molecules bind per Fhit dimer; identifying two additional
      adenosine-binding sites on the dimer surface; and illustrating that His-98 is
      positioned to donate a hydrogen bond to the scissile bridging oxygen of ApppA
      substrates. The form of Fhit bound to two ApppA substrates would present to the
      cell a dramatically phosphorylated surface, prominently displaying six phosphate
      groups and two adenosine moieties in place of a deep cavity lined with
      histidines, arginines, and glutamines.

PMID- 9576910
TI  - Snapshot of a phosphorylated substrate intermediate by kinetic crystallography.
AB  - The ATP-dependent enzyme dethiobiotin synthetase from Escherichia coli catalyses
      the formation of dethiobiotin from CO2 and 7, 8-diaminopelargonic acid. The
      reaction is initiated by the formation of a carbamate and proceeds through a
      phosphorylated intermediate, a mixed carbamic phosphoric anhydride. Here, we
      report the crystal structures at 1.9- and 1.6-A resolution, respectively, of the
      enzyme-MgATP-diaminopelargonic acid and enzyme-MgADP-carbamic-phosphoric acid
      anhydride complexes, observed by using kinetic crystallography. Reaction
      initiation by addition of either NaHCO3 or diaminopelargonic acid to crystals
      already containing cosubstrates resulted in the accumulation of the
      phosphorylated intermediate at the active site. The phosphoryl transfer step
      shows inversion of the configuration at the phosphorus atom, consistent with an
      in-line attack by the carbamate oxygen onto the phosphorus atom of ATP. A key
      feature in the structure of the complex of the enzyme with the reaction
      intermediate is two magnesium ions, bridging the phosphates at the cleavage site.
      These magnesium ions compensate the negative charges at both phosphate groups
      after phosphoryl transfer and contribute to the stabilization of the reaction
      intermediate.

PMID- 9576909
TI  - The role of charged residues mediating low affinity protein-protein recognition
      at the cell surface by CD2.
AB  - Insights into the structural basis of protein-protein recognition have come
      principally from the analysis of proteins such as antibodies, hormone receptors,
      and proteases that bind their ligands with relatively high affinity (Ka
      approximately 10(9) M-1). In contrast, few studies have been done on the very low
      affinity interactions mediating cell adhesion and cell-cell recognition. As a
      site of protein-protein recognition, the ligand binding face of the T lymphocyte
      cell-cell recognition molecule, CD2, which binds its ligands 10(4)- to 10(5)-fold
      more weakly than do antibodies and proteases, is unusual in being both very flat
      and highly charged. An analysis of the effect of mutations and ionic strength on
      CD2 binding to its ligand, CD48, indicates that these charged residues contribute
      little, if any, binding energy to this interaction. However, the loss of these
      charged residues is shown to markedly reduce ligand-binding specificity. Thus,
      the charged residues increase the specificity of CD2 binding without increasing
      the affinity. This phenomenon is likely to result from a requirement for
      electrostatic complementarity between charged binding surfaces to compensate for
      the removal, upon binding, of water interacting with the charged residues. It is
      proposed that this mode of recognition is highly suited to biological
      interactions requiring a low affinity because it uncouples increases in
      specificity from increases in affinity.

PMID- 9576911
TI  - Crystal structure of the channel-forming polypeptide antiamoebin in a membrane
      mimetic environment.
AB  - Crystals of an ion-channel-forming peptaibol peptide in a partial membrane
      environment have been obtained by cocrystallizing antiamoebin with n-octanol. The
      antiamoebin molecule has a bent helical conformation very similar to that
      established for Leu-zervamicin, despite a significantly different sequence for
      residues 1-8. The bent helices assemble to form a polar channel in the shape of
      an hour glass that is quite comparable to that of Leu-zervamicin. The molecules
      of cocrystallized octanol are found in two different areas with respect to the
      assembly of peptide molecules. One octanol molecule mimics a membrane segment
      along the hydrophobic exterior of the channel assembly. The other octanol
      molecules fill the channel in such a way that their OH termini satisfy the C==O
      moieties directed into the interior of the channel. Structure parameters for C82
      H27 N17 O20(.3) C8H18O are space group P2(1) 2(1) 2(1), a = 9.143(2) A, b =
      28.590(8) A, c = 44.289(8) A, Z = 4, agreement factor R1 = 11.95% for 4,113
      observed reflections [>4sigma(F)], resolution approximately 1.0 A.

PMID- 9576912
TI  - In vitro site-specific integration of bacteriophage DNA catalyzed by a
      recombinase of the resolvase/invertase family.
AB  - The genome of the broad host range Streptomyces temperate phage, phiC31, is known
      to integrate into the host chromosome via an enzyme that is a member of the
      resolvase/invertase family of site-specific recombinases. The recombination
      properties of this novel integrase on the phage and Streptomyces ambofaciens
      attachment sites, attP and attB, respectively, were investigated in the
      heterologous host, Escherichia coli, and in an in vitro assay by using purified
      integrase. The products of attP/B recombination, i.e., attL and attR, were
      identical to those obtained after integration of the prophage in S. ambofaciens.
      In the in vitro assay only buffer, purified integrase, and DNAs encoding attP and
      attB were required. Recombination occurred irrespective of whether the substrates
      were supercoiled or linear. A mutant integrase containing an S12F mutation was
      completely defective in recombination both in E. coli and in vitro. No
      recombination was observed between attB/attB, attP/attP, attL/R, or any
      combination of attB or attP with attL or attR, suggesting that excision of the
      prophage (attL/R recombination) requires an additional phage- or Streptomyces
      encoded factor. Recombination could occur intramolecularly to cause deletion
      between appropriately orientated attP and attB sites. The results show that
      directionality in phiC31 integrase is strictly controlled by nonidentical
      recombination sites with no requirement to form the topologically defined
      structures that are more typical of the resolvases/invertases.

PMID- 9576913
TI  - Directed evolution of an aspartate aminotransferase with new substrate
      specificities.
AB  - The substrate specificity of aspartate aminotransferase was successfully modified
      by directed molecular evolution using a combination of DNA shuffling and
      selection in an auxotrophic Escherichia coli strain. After five rounds of
      selection, one of the evolved mutants showed a 10(5)-fold increase in the
      catalytic efficiency (kcat/Km) for beta-branched amino and 2-oxo acids and a 30
      fold decrease in that for the native substrates compared with the wild-type
      enzyme. The mutant had 13 amino acid substitutions, 6 of which contributed 80-90%
      to the total effect. Five of these six substitutions were conserved among the
      five mutants that showed the highest activity for beta-branched substrates.
      Interestingly, only one of the six functionally important residues is located
      within a distance of direct interaction with the substrate, supporting the idea
      that rational design of the substrate specificity of an enzyme is very difficult.
      The present results show that directed molecular evolution is a powerful
      technique for enzyme redesign if an adequate selection system is applied.

PMID- 9576914
TI  - PD-loop: a complex of duplex DNA with an oligonucleotide.
AB  - A stable complex between duplex DNA and an oligonucleotide is assembled with the
      aid of a DNA synthetic mimic, peptide nucleic acid (PNA). Homopyrimidine PNAs are
      known to invade into short homopurine tracts in duplex DNA forming P-loops. We
      have found that P-loops, formed at two closely located purine tracts in the same
      DNA strand separated by a mixed purine-pyrimidine sequence, merge and open the
      double helix between them. The opposite DNA strand, which is not bound with PNA,
      exposes and becomes accessible for complexing with an oligonucleotide via Watson
      Crick pairing. As a result, the PD-loop emerges, which consists of locally open
      duplex DNA, PNA "openers," and an oligonucleotide. The PD-loop stability and
      sequence specificity are demonstrated by affinity capture of duplex DNAs by using
      biotinylated oligonucleotides and streptavidin-covered magnetic beads. The type
      of complex formed by PNAs, an oligonucleotide and duplex DNA we describe, opens
      ways for development of various in vitro and in situ hybridization techniques
      with duplex DNA and may find applications in DNA nanotechnology and genomics.

PMID- 9576915
TI  - Persistence of an alternate chromatin structure at silenced loci in the absence
      of silencers.
AB  - In Saccharomyces cerevisiae, genes placed near telomeres or the silent HML and
      HMR mating-type loci are transcriptionally repressed by a heterochromatin-like
      structure. We have generated nonreplicating DNA rings by recombination in vivo to
      examine the role of chromosomal context on transcriptional repression.
      Specifically, recombination at HMR was used to produce rings that lacked the E
      and I silencers. An altered level of DNA supercoiling was observed in these rings
      but not in comparable rings from derepressed loci. Our results indicate that a
      repressive chromatin structure persists in an extrachromosomal environment
      immediately following removal of the cis-acting control elements. Examination of
      both chromatin footprints and DNA sequence dependence revealed that changes in
      nucleosome number could account for the topology shifts. Upon continued cell
      growth, the differences in supercoiling were lost and transcriptional competence
      was restored. These results show that silencers are required for sustained
      persistence of repressive chromatin structure, even in the absence of DNA
      replication.

PMID- 9576916
TI  - From estrogen to androgen receptor: a new pathway for sex hormones in prostate.
AB  - While all three coactivators ARA70, steroid receptor coactivator 1, and RAC3/ACTR
      can enhance androgen receptor (AR) transcriptional activity at 1 nM
      dihydrotestosterone, we here demonstrate that only ARA70 can induce AR
      transcriptional activity >30-fold in the presence of 10 nM 17beta-estradiol (E2),
      but not diethylstilbestrol. The significance of this newly described E2-induced
      AR transcriptional activity in DU145 human prostate cancer cells was further
      strengthened by finding patients with Reifenstein partial-androgen-insensitive
      syndrome that fail in the E2-AR-ARA70 pathway. Together, our data suggest, for
      the first time, testosterone/dihydrotestosterone may not be the only ligands for
      the AR. E2 represents another important natural ligand for AR that may play an
      essential role for the AR function and the development of the male reproductive
      system.

PMID- 9576917
TI  - Evidence of high levels of methylglyoxal in cultured Chinese hamster ovary cells.
AB  - Methylglyoxal is an alpha-ketoaldehyde and dicarbonyl formed in cells as a side
      product of normal metabolism. Endogenously produced dicarbonyls, such as
      methylglyoxal, are involved in numerous pathogenic processes in vivo, including
      carcinogenesis and advanced glycation end-product formation; advanced glycation
      end-products are contributors to the pathophysiology of aging and chronic
      diabetes. Despite recent advances in understanding of the systemic effects of
      methylglyoxal, the full significance of this compound remains unknown. Herein we
      provide evidence that the majority of the methylglyoxal present in vivo is bound
      to biological ligands. The basis for our finding is an experimental approach that
      provides a measure of the bound methylglyoxal present in living systems, in this
      instance Chinese hamster ovary cells; with our approach, as much as 310 microM
      methylglyoxal was detected, 100- to 1,000-fold more than observed previously in
      biological systems. Several artifacts were considered before concluding that the
      methylglyoxal was associated with cellular structures, including phosphate
      elimination from triose phosphates, carbohydrate degradation under the assay
      conditions, and interference from the derivatizing agent used as part of the
      assay procedure. A major source of the recovered methylglyoxal is most probably
      modified cellular proteins. With methylglyoxal at about 300 microM, 0.02% of
      cellular amino acid residues could be modified. As few as one or two "hits" with
      methylglyoxal per protein molecule have previously been reported to be sufficient
      to cause protein endocytosis and subsequent degradation. Thus, 5-10% of cellular
      proteins may be modified to physiologically significant levels.

PMID- 9576918
TI  - Physical interaction between retinoic acid receptor and the oncoprotein myb
      inhibits retinoic acid-dependent transactivation.
AB  - The c-myb protooncogene is predominantly expressed in hematopoietic cells and
      plays a vital role in hematopoiesis. Retinoic acid (RA) is able to induce
      differentiation of several hematopoietic cells. This differentiation is linked to
      decreased c-myb expression, suggesting that retinoid receptors (RAR/RXR) may down
      regulate c-myb gene expression. Furthermore, recent data indicate that RAR
      inhibits the function of the Myb protein itself. In addition, the Myb-Ets
      oncogenic fusion protein has been shown to inhibit transcriptional activation by
      RAR and thyroid hormone receptor. Myb-Ets also antagonizes the biological
      response of erythrocytic progenitor cells to RA and thyroid hormone. This
      prompted us to investigate a possible cross talk between RAR and Myb. Here, we
      demonstrate that RA inhibits the expression of the endogenous Myb target gene tom
      1. Conversely, Myb functions as a potent inhibitor of RA-induced biological
      responses. Functional analysis of Myb mutants in transfection studies revealed
      that the Myb DNA-binding domain (DBD) is necessary for repression whereas the
      transactivation domain is dispensable. Furthermore, we show that v-Myb and RAR
      interact in vitro and in vivo. This interaction requires the DBD of RAR. In
      contrast, glutathione S-transferase-pulldown assays with v-Myb mutants indicate
      that the DBD and the C terminus of Myb directly interact with RAR. Our results
      suggest that the physical interaction between Myb and RAR may play a role in the
      regulation of hematopoietic gene expression.

PMID- 9576919
TI  - On the thermodynamic hypothesis of protein folding.
AB  - The validity of the thermodynamic hypothesis of protein folding was explored by
      simulating the evolution of protein sequences. Simple models of lattice proteins
      were allowed to evolve by random point mutations subject to the constraint that
      they fold into a predetermined native structure with a Monte Carlo folding
      algorithm. We employed a simple analytical approach to compute the probability of
      violation of the thermodynamic hypothesis as a function of the size of the
      protein, the fraction of the total number of possible conformations which are
      kinetically accessible, and the roughness of the free-energy landscape. It was
      found that even if the folding is under kinetic control, the sequence will evolve
      so that the native state is most often the state of minimum free energy.

PMID- 9576920
TI  - Conduction-band-edge ionization thresholds of DNA components in aqueous solution.
AB  - Numerous investigations have focused on DNA damage induced by ionizing radiation;
      however, photoionization threshold energies of nucleic acid components in aqueous
      solution are not known. Herein, data from gas-phase photoelectron experiments
      have been combined with results from self-consistent field and post-self
      consistent field molecular orbital calculations and with theoretical Gibbs free
      energies of hydration to describe aqueous ionization energies of 2'
      deoxythymidine 5'-phosphate (5'-dTMP-) and 2'-deoxycytidine 5'-phosphate (5'-dCMP
      ). For the test molecules, indole and tryptophan, this approach yields aqueous
      ionization energies (4.46 and 4.58 eV, respectively) in agreement with
      experimental values (4. 35 and 4.45 eV). When uridine and 2'-deoxythymidine
      ionization energies are evaluated, the results agree with recent data from 193-nm
      laser measurements indicating that uridine ionization occurs via a one-photon
      event. For 5'-dCMP- and 5'-dTMP-, a comparison of aqueous ionization energies
      with gas-phase ionization potentials (IPs) indicates that hydration alters the
      relative energies of ionization events. In the gas phase, phosphate vertical IPs
      are approximately 1.3 eV smaller than base IPs. In aqueous solution, the base and
      phosphate ionization energies are more similar, and only differ by approximately
      0.5 eV. For 5'-dCMP- and 5'-dTMP-, the increased favorableness of base
      ionization, which accompanies hydration, is consistent with experimental data
      indicating that, at 77 K in aqueous perchlorate glasses, the primary
      photoionization pathway involves base ionization followed by deprotonation.

PMID- 9576921
TI  - Signal-dependent translation of a regulatory protein, Bcl-3, in activated human
      platelets.
AB  - Circulating human platelets lack nuclei, cannot synthesize mRNA, and are
      considered incapable of regulated protein synthesis. We found that thrombin
      activated, but not resting, platelets synthesize Bcl-3, a member of the IkappaB
      alpha family of regulatory proteins. The time- and concentration-dependent
      generation of Bcl-3 in platelets signaled by thrombin was blocked by
      translational inhibitors, by rapamycin, and by inhibitors of phosphatidylinositol
      3-kinase, indicating that it occurs via a specialized translational control
      pathway that involves phosphorylation of the inhibitory protein 4E-BP1. After its
      synthesis in activated platelets Bcl-3 binds to the SH3 domain of Fyn (p59(fyn)),
      a Src-related tyrosine kinase. This, along with its expression in anucleate
      cells, suggests that Bcl-3 has previously unrecognized functions aside from
      modulation of transcription. We also demonstrate that platelets synthesize and
      secrete numerous proteins besides Bcl-3 after they adhere to fibrinogen, which
      mediates adhesion and outside-in signaling of these cells by engagement of
      alphaIIb/beta3 integrin. Taken together, these data demonstrate that regulated
      synthesis of proteins is a signal-dependent activation response of human
      platelets.

PMID- 9576922
TI  - Alzheimer's-specific effects of soluble beta-amyloid on protein kinase C-alpha
      and -gamma degradation in human fibroblasts.
AB  - Alzheimer's disease (AD) is a multifactorial disease in which beta-amyloid
      peptide (betaAP) plays a critical role. We report here that the soluble fraction
      1-40 of betaAP differentially degrades protein kinase C-alpha and -gamma
      (PKCalpha and PKCgamma) isoenzymes in normal (age-matched controls, AC) and AD
      fibroblasts most likely through proteolytic cascades. Treatment with nanomolar
      concentrations of betaAP(1-40) induced a 75% decrease in PKCalpha, but not
      PKCgamma, immunoreactivity in AC fibroblasts. In the AD fibroblasts, a 70%
      reduction of the PKCgamma, but not PKCalpha, immunoreactivity was observed after
      betaAP treatment. Preincubation of AC or AD fibroblasts with 50 microM
      lactacystine, a selective proteasome inhibitor, prevented beta-AP(1-40)-mediated
      degradation of PKCalpha in the AC cells, and PKCgamma in the AD fibroblasts. The
      effects of betaAP(1-40) on PKCalpha in AC fibroblasts were prevented by
      inhibition of protein synthesis and reversed by PKC activation. A 3-hr treatment
      with 100 nM phorbol 12-myristate 13-acetate restored the PKCalpha signal in
      treated AC cells but it did not reverse the effects of betaAP(1-40) on PKCgamma
      in the AD fibroblasts. Pretreatment with the protein synthesis inhibitor,
      cycloheximide (CHX, 100 microM), inhibited the effects of betaAP(1-40) on
      PKCalpha and blocked the rescue effect of phorbol 12-myristate 13-acetate in AC
      fibroblasts but did not modify PKCgamma immunoreactivity in AD cells. These
      results suggest that betaAP(1-40) differentially affects PKC regulation in AC and
      AD cells via proteolytic degradation and that PKC activation exerts a protective
      role via de novo protein synthesis in normal but not AD cells.

PMID- 9576924
TI  - Dopamine-induced recruitment of dopamine D1 receptors to the plasma membrane.
AB  - The recruitment of G protein-coupled receptors from the cytoplasm to the plasma
      membrane generally is believed to be a constitutive process. We show here by the
      use of both confocal microscopy and subcellular fractionation that, for at least
      one such receptor, this recruitment is regulated and not constitutive. Cells from
      a proximal tubular-like cell line, LLCPK1 cells, were incubated with either a D1
      agonist, a dopamine precursor, or an inhibitor of dopamine metabolism to increase
      dopamine availability in the cell. Each of the three procedures led to a rapid
      translocation of dopamine D1 receptors from the cytosol to the plasma membrane.

PMID- 9576923
TI  - STAT3 complements defects in an interferon-resistant cell line: evidence for an
      essential role for STAT3 in interferon signaling and biological activities.
AB  - STAT proteins play critical roles in the signal transduction pathways for various
      cytokines. The type I interferons (IFNalpha/beta) promote the DNA-binding
      activity of the transcription factors STAT1, STAT2, and STAT3. Although the
      requirement for STAT1 and STAT2 in IFNalpha/beta signaling and action is well
      documented, the biological importance of STAT3 to IFN action has not yet been
      addressed. We found that STAT3 plays a critical role in signal transduction by
      IFNalpha/beta. A human cell line that is resistant to the antiviral and
      antiproliferative activities of IFN but is still IFN-responsive by virtue of
      STAT1 and STAT2 activation was found to be defective in STAT3 activation and in
      induction of NF-kappaB DNA-binding activity. Expression of STAT3 in these
      resistant cells complemented these signaling defects and also markedly increased
      cellular sensitivity to the antiviral and antiproliferative effects of IFN.
      Because STAT3 is involved in the induction of NF-kappaB DNA-binding activity and
      in the induction of antiviral and antiproliferative activity, our results place
      STAT3 as an important upstream element in type I IFN signal transduction and in
      the induction of biological activities. Therefore, our results indicate that
      STAT1 and STAT2 are not the only STATs required for the expression of the key
      biological activities of IFNalpha/beta.

PMID- 9576925
TI  - Angiostatin induces endothelial cell apoptosis and activation of focal adhesion
      kinase independently of the integrin-binding motif RGD.
AB  - Angiostatin, a fragment of plasminogen, has been identified and characterized as
      an endogenous inhibitor of neovascularization. We show that angiostatin treatment
      of endothelial cells in the absence of growth factors results in an increased
      apoptotic index whereas the proliferation index is unchanged. Angiostatin also
      inhibits migration and tube formation of endothelial cells. Angiostatin treatment
      has no effect on growth factor-induced signal transduction but leads to an RGD
      independent induction of the kinase activity of focal adhesion kinase, suggesting
      that the biological effects of angiostatin relate to subversion of adhesion
      plaque formation in endothelial cells.

PMID- 9576926
TI  - Plasma membrane localization is required for RGS4 function in Saccharomyces
      cerevisiae.
AB  - RGS4, a mammalian GTPase activating protein for G protein alpha subunits, was
      identified by its ability to inhibit the pheromone response pathway in
      Saccharomyces cerevisiae. To define regions of RGS4 necessary for its function in
      vivo, we assayed mutants for activity in this system. Deletion of the N-terminal
      33 aa of RGS4 (Delta1-33) yielded a nonfunctional protein and loss of plasma
      membrane localization. These functions were restored by addition of a C-terminal
      membrane-targeting sequence to RGS4 (Delta1-33). Thus, plasma membrane
      localization is tightly coupled with the ability of RGS4 to inhibit signaling.
      Fusion of the N-terminal 33 aa of RGS4 to green fluorescent protein was
      sufficient to localize an otherwise soluble protein to the plasma membrane,
      defining this N-terminal region as a plasma membrane anchorage domain. RGS4 is
      palmitoylated, with Cys-2 and Cys-12 the likely sites of palmitoylation.
      Surprisingly, mutation of the cysteine residues within the N-terminal domain of
      RGS4 did not affect plasma membrane localization in yeast or the ability to
      inhibit signaling. Features of the N-terminal domain other than palmitoylation
      are responsible for the plasma membrane association of RGS4 and its ability to
      inhibit pheromone response in yeast.

PMID- 9576927
TI  - Signal transduction and activator of transcription (STAT) protein-dependent
      activation of angiotensinogen promoter: a cellular signal for hypertrophy in
      cardiac muscle.
AB  - The role of the peptide hormone angiotensin (AngII) in promoting myocardial
      hypertrophy is well documented. Our studies demonstrate that AngII uses a
      signaling pathway in cardiac myocytes in which the promoter of the gene encoding
      its prohormone, angiotensinogen, serves as the target site for activated signal
      transduction and activator of transcription (STAT) proteins. Gel mobility-shift
      assay revealed that STAT3 and STAT6 are selectively activated by AngII treatment
      of cardiomyocytes in culture and bind to a sequence motif (St-domain) in the
      angiotensinogen promoter to activate its transcription in transient transfection
      assay. We have also observed a dramatic increase in the St-domain binding
      activity of STAT proteins in the hypertrophied heart of the genetically
      hypertensive rat relative to that of the aged-matched normotensive strain WKY,
      providing a compelling argument in favor of the linkage of STAT pathway to the
      heart tissue autocrine AngII loop. These studies thus uncover a mechanism by
      which the activation of a selective set of STATs underlies mobilization of the
      gene activation program intrinsic to cardiac hypertrophy.

PMID- 9576928
TI  - Fas-induced proteolytic activation and intracellular redistribution of the stress
      signaling kinase MEKK1.
AB  - The stress-activated protein kinase (SAPK, alternatively JNK) is activated
      rapidly by cell stress stimuli such as inflammatory cytokines and oxidative
      stress, and more slowly by the initiation of the apoptotic cell death response by
      events such as ligation of the Fas protein. Mitogen-activated protein kinase/Erk
      kinase kinase-1 (MEKK1) is an activator of SAPK, serving as a SAPK-kinase-kinase
      through intermediate phosphorylation of the SAPK kinase SEK1. By sequencing
      proteolytic cleavage products of MEKK1, we found that the proapoptotic protease
      caspase 3 (CPP32) cleaves MEKK1 after residue D68 both in vivo and in vitro.
      Cleavage of MEKK1 after D68 is blocked by viral and chemical protease inhibitors.
      Cleavage of MEKK1 at D68 changes the intracellular distribution of the protein
      from a Triton-insoluble compartment to a Triton-soluble compartment, reflected in
      a redistribution from a particulate to a diffuse cytoplasmic staining seen by
      immunofluorescence. Activation of both SAPK and MEKK1 after Fas ligation is
      prevented by both viral and chemical caspase 3 inhibitors, which in contrast fail
      to block activation of SAPK by rapidly acting cell stresses. Stress factor
      induced SAPK signaling is not dependent on caspase 3 function. We propose that
      two mechanisms of stress signaling through MEKK1 exist. One is rapid, independent
      of proteases, and occurs in the particulate Triton-insoluble compartment. The
      other is more slowly activated and involves liberation of particulate MEKK1 by
      proteolytic cleavage and activation by caspase 3.

PMID- 9576929
TI  - Polyreactive anti-DNA monoclonal antibodies and a derived peptide as vectors for
      the intracytoplasmic and intranuclear translocation of macromolecules.
AB  - Naturally occurring polyreactive anti-DNA mAbs derived from a nonimmunized (NZB x
      NZW)F1 mouse with spontaneous lupus erythematosus penetrated and accumulated in
      the nuclei of a variety of cultured cells. These mAbs and their F(ab')2 and Fab'
      fragments, covalently coupled to fluorescein, peroxidase, or a 15-mer
      polynucleotide, also translocated to the cell nuclei. A 30-amino acid peptide
      corresponding to the combined sequences of the complementary-determining regions
      2 and 3 of the heavy chain variable region of one mAb was able to penetrate into
      the cytoplasm and nucleus of cells of several lines. This peptide recognized DNA
      and was strongly polyreactive. Streptavidin-peroxidase conjugates complexed with
      the N-biotinylated peptide were rapidly translocated into cells. Similarly,
      peroxidase or anti-peroxidase polyclonal antibodies covalently coupled to the N
      cysteinylated peptide through an heterobifunctional maleimide cross-linker were
      also rapidly internalized and frequently accumulated in nuclei. The peptide
      carrying 19 lysine residues at its N-terminal was highly effective in
      transfecting 3T3 cells with a plasmid containing the luciferase gene. Thus,
      penetrating mAbs and derived peptides are versatile vectors for the intracellular
      delivery of proteins and genes.

PMID- 9576930
TI  - The rate of telomere sequence loss in human leukocytes varies with age.
AB  - A gradual loss of telomeric repeat sequences with aging previously has been noted
      in normal adult tissues, and this process has been implicated in cell senescence.
      No data exist that address the rate of telomere shortening in normal human cells
      within families or early in life. To address these questions, we measured
      telomere lengths in peripheral blood leukocytes (PBLs) from 75 members of 12
      families and in a group of unrelated healthy children who were 5-48 months old.
      Here we report the surprising observation that rates of telomere attrition vary
      markedly at different ages. Telomeric repeats are lost rapidly (at a rate of >1
      kilobase per year) from the PBLs of young children, followed by an apparent
      plateau between age 4 and young adulthood, and by gradual attrition later in
      life. These data suggest that the loss of telomeric repeats in hematopoietic
      cells is a dynamic process that is differentially regulated in young children and
      adults. Our results have implications for current models of how telomeric
      sequences are lost in normal somatic cells and suggest that PBLs are an excellent
      tissue to investigate how this process is controlled.

PMID- 9576931
TI  - Development of normal mice from metaphase I oocytes fertilized with primary
      spermatocytes.
AB  - Primary spermatocytes are the male germ cells before meiosis I. To examine
      whether these 4n diploid cells are genetically competent to fertilize oocytes and
      support full embryo development, we introduced the nuclei of pachytene/diplotene
      spermatocytes into oocytes that were arrested in prophase I (germinal vesicle
      stage), metaphase I, or metaphase II (Met II). Both the paternal and maternal
      chromosomes then were allowed to undergo meiosis synchronously until Met II. In
      the first and second groups, the paternal and maternal chromosomes had
      intermingled to form a large Met II plate, which was then transferred into a
      fresh enucleated Met II oocyte. In the third group, the paternal Met II
      chromosomes were obtained by transferring spermatocyte nuclei into Met II oocytes
      twice. After activation of the Met II oocytes that were produced, those
      microfertilized at metaphase I showed the best developmental ability in vitro,
      and three of these embryos developed into full-term offspring after embryo
      transfer. Two pups (one male and one female) were proven to be fertile. This
      finding provides direct evidence that the nuclei of male germ cells acquire the
      ability to fertilize oocytes before the first meiotic division.

PMID- 9576932
TI  - Diapause-specific gene expression in pupae of the flesh fly Sarcophaga
      crassipalpis.
AB  - Several cDNAs isolated from brains of diapausing pupae of the flesh fly,
      Sarcophaga crassipalpis, show expression patterns unique to diapause. To isolate
      such cDNAs a diapause pupal brain cDNA library was screened by using an
      elimination hybridization technique, and cDNAs that did not hybridize with cDNA
      probes constructed from the RNA of nondiapausing pupae were selected for further
      screening. The 95 clones that did not hybridize in the initial library screen
      were selected for further characterization. These clones were then screened
      against diapause and nondiapause pupal poly(A)+ Northern blots. The secondary
      screen identified 4 diapause-up-regulated clones, 7 diapause-down-regulated
      clones, 8 clones expressed equally in both diapause and nondiapause, and 75
      clones without detectable expression. The diapause-up-regulated and down
      regulated clones were further characterized by partial DNA sequencing and
      identity searches by using GenBank. Identities between our cloned cDNAs and other
      genes included those linked to cell cycle progression, stress responses, and DNA
      repair processes. The results suggest that insect diapause is not merely a
      shutdown of gene expression but is a unique, developmental pathway characterized
      by the expression of a novel set of genes.

PMID- 9576933
TI  - Glucocorticoids are insufficient for neonatal gene induction in the liver.
AB  - Glucocorticoids and their receptor (GR) play a key role in perinatal gene
      induction. In the liver, the GR is essential for the neonatal induction of a
      number of genes, including that coding for tyrosine aminotransferase (TAT). To
      assess the function of the GR in the perinatal period, we have compared the
      activity of two types of glucocorticoid responsive elements in transgenic mice;
      one is the Tat gene glucocorticoid-responsive unit (GRU), an assembly of numerous
      binding sites for transcription factors, including the GR; the other is a simple
      dimer of high-affinity GR binding sites (GREs). Both elements confer strong
      glucocorticoid response in the adult liver. However, only the Tat GRUs are able
      to promote neonatal induction; the GRE dimer is unresponsive. Because this dimer
      is responsive to glucocorticoid administration in the neonate, the absence of
      neonatal induction is not due to the inactivity of the GR at this stage. At
      birth, the neonate has to withstand a brief period of starvation and
      hypoglycemia, a nutritional and hormonal situation that resembles fasting in the
      adult. In transgenic mice, the responses at birth and after fasting in the adult
      are similar: the Tat GRUs but not the dimeric GREs are activated. Our results
      show that, in rodents, glucocorticoids are not sufficient for neonatal gene
      induction in the liver and support the conclusion that the hypoglycemia at birth
      is the main trigger for expression.

PMID- 9576934
TI  - Wnt signaling and transcriptional control of Siamois in Xenopus embryos.
AB  - The Wnt-inducible homeobox gene Siamois is expressed in Xenopus embryos before
      gastrulation and is necessary for formation of the Spemann organizer. Here we
      show that 5'-flanking sequences of the Siamois coding region can specifically
      activate a heterologous reporter gene in dorsovegetal cells, thus mimicking
      Siamois's endogenous expression. A 245-bp DNA fragment is sufficient for
      activation by both Wnts and endogenous inducers. A dominant negative form of
      Xenopus T cell-specific factor 3 (XTCF-3) inhibited promoter activity, indicating
      that T cell-specific factor (TCF)/lymphocyte enhancer binding factor 1 (LEF-1)
      signaling is necessary for regulation of Siamois. Mutagenesis of two individual
      TCF sites in the -245 promoter revealed that the proximal, but not distal, site
      is necessary for dorsovegetal activation. These observations suggest that Siamois
      is directly regulated by TCFs during dorsoventral axis determination. Further
      deletion analysis identified a positive regulatory region that is required for
      dorsal activation, but not for Wnt inducibility, of the promoter. We also present
      evidence for autoregulation of Siamois transcription. Furthermore, the Siamois
      promoter was activated by Wnt signaling in 293T tissue culture cells,
      demonstrating that regulation of the promoter is functionally conserved.

PMID- 9576935
TI  - Biodiversity and ecosystem functioning: a mechanistic model.
AB  - Recent experiments have provided some evidence that loss of biodiversity may
      impair the functioning and sustainability of ecosystems. However, we still lack
      adequate theories and models to provide robust generalizations, predictions, and
      interpretations for such results. Here I present a mechanistic model of a
      spatially structured ecosystem in which plants compete for a limiting soil
      nutrient. This model shows that plant species richness does not necessarily
      enhance ecosystem processes, but it identifies two types of factors that could
      generate such an effect: (i) complementarity among species in the space they
      occupy below ground and (ii) positive correlation between mean resource-use
      intensity and diversity. In both cases, the model predicts that plant biomass,
      primary productivity, and nutrient retention all increase with diversity, similar
      to results reported in recent field experiments. These two factors, however, have
      different implications for the understanding of the relationship between
      biodiversity and ecosystem functioning. The model also shows that the effect of
      species richness on productivity or other ecosystem processes is masked by the
      effects of physical environmental parameters on these processes. Therefore,
      comparisons among sites cannot reveal it, unless abiotic conditions are very
      tightly controlled. Identifying and separating out the mechanisms behind
      ecosystem responses to biodiversity should become the focus of future
      experiments.

PMID- 9576937
TI  - Intraspecific heterochrony and life history evolution: decoupling somatic and
      sexual development in a facultatively paedomorphic salamander.
AB  - Morphological features such as size and shape are the most common focus in
      studies of heterochronic change. Frequently, these easily observed and measured
      features are treated as a major target of selection, potentially ignoring traits
      more closely related to fitness. We question the primacy of morphological data in
      studies of heterochrony, and instead suggest that principal sources of fitness,
      such as life history characteristics, are not only the chief targets of
      selection, but changes in them may necessitate changes in other (subordinate)
      elements of the organism. We use an experimental approach to investigate the
      timing of metamorphosis and maturation in a facultatively paedomorphic
      salamander, Ambystoma talpoideum. We determine that individuals possessing the
      well-known paedomorphic phenotype are peramorphic with regard to maturation,
      through the process of predisplacement (an earlier onset of maturation).
      Combining the well studied ecology of dimorphic A. talpoideum populations with
      theories of heterochronic mechanisms and life history evolution, we conclude that
      age at maturation is the principal target of selection and that morphological
      changes are secondary effects. Increased attention to the intimate connection
      between life history evolution and heterochrony is the most promising route to a
      better understanding of both.

PMID- 9576936
TI  - Nucleotide sequence diversity at the alcohol dehydrogenase 1 locus in wild barley
      (Hordeum vulgare ssp. spontaneum): an evaluation of the background selection
      hypothesis.
AB  - The background selection hypothesis predicts a reduction in nucleotide site
      diversity and an excess of rare variants, owing to linkage associations with
      deleterious alleles. This effect is expected to be amplified in species that are
      predominantly self-fertilizing. To examine the predictions of the background
      selection hypothesis in self-fertilizing species, we sequenced 1,362 bp of adh1,
      a gene for alcohol dehydrogenase (Adh; alcohol:NAD+ oxidoreductase, EC 1.1.1.1),
      in a sample of 45 accessions of wild barley, Hordeum vulgare ssp. spontaneum,
      drawn from throughout the species range. The region sequenced included 786 bp of
      exon sequence (part of exon 4, all of exons 5-9, and part of exon 10) and 576 bp
      of intron sequence (all of introns 4-9). There were 19 sites polymorphic for
      nucleotide substitutions, 8 in introns, and 11 in exons. Of the 11 nucleotide
      substitutions in codons, 4 were synonymous and 7 were nonsynonymous, occurring
      uniquely in the sample. There was no evidence of recombination in the region
      studied, and the estimated effective population size (Ne) based on synonymous
      sites was approximately 1.8-4.2 x 10(5). Several tests reveal that the pattern of
      nonsynonymous substitutions departs significantly from neutral expectations.
      However, the data do not appear to be consistent with recovery from a population
      bottleneck, recent population expansion, selective sweep, or strong positive
      selection. Though several features of the data are consistent with background
      selection, the distributions of polymorphic synonymous and intron sites are not
      perturbed toward a significant excess of rare alleles as would be predicted by
      background selection.

PMID- 9576938
TI  - A test of the background selection hypothesis based on nucleotide data from
      Drosophila ananassae.
AB  - We estimated DNA sequence variation within and between four populations of
      Drosophila ananassae at Om(1D) and vermilion (v) by using single-strand
      conformation polymorphism analysis and direct DNA sequencing. Om(1D) is located
      on the X chromosome in a region with a normal recombination rate; v is in a
      region of low recombination. In each population, levels of nucleotide diversity
      at v are reduced 10- to 25-fold relative to those at Om(1D). Divergence between
      D. ananassae and its sibling species D. pallidosa, however, is comparable for
      both loci. This lack of correlation between levels of polymorphism and divergence
      led to the rejection of a constant-rate, neutral model. To distinguish among
      alternative models, we propose a test of the background selection hypothesis
      based on the observed pattern of differentiation between populations. Although
      the degree of differentiation (measured by FST) among all pairs of subpopulations
      is similar at Om(1D), we found substantial differences at v. The two northern
      populations from Burma and Nepal are very homogeneous, whereas comparisons
      between northern and southern populations (e.g., between Nepal and middle India)
      produced large FST values. A coalescent-based simulation of the background
      selection model (in a geographically structured species with a finite number of
      demes) showed that the observed homogeneity among the northern populations is
      inconsistent with the background selection hypothesis. Instead, it may have been
      caused by a recent hitchhiking event that was limited to the northern species
      range.

PMID- 9576940
TI  - Screening for overlapping bacterial artificial chromosome clones by PCR analysis
      with an arbitrary primer.
AB  - In this article, we used PCR analysis with arbitrary primers (AP-PCR) to screen
      for overlapping bacterial artificial chromosome (BAC) clones and assembly of
      contigs. A rice BAC library with three genome equivalents was used to prepare
      pooled BAC DNA. Twenty-two arbitrary primers were used to survey the pooled BAC
      DNAs and individual BAC DNAs. Each primer identified 1-10 loci, and the average
      was 4.4 loci. There were 1-5 overlapping clones in each locus, and the average
      was 2.5 clones. A total of 245 BAC clones were identified as overlapping by AP
      PCR and the identities were confirmed by DNA-DNA hybridization. The 245 BAC
      clones were then assembled into 80 contigs and 17 single-clone loci. The results
      indicated that PCR analysis with arbitrary primers is a powerful tool in
      screening for overlapping BAC clones with high accuracy and efficiency. The use
      of AP-PCR analysis should speed up the construction of physical maps of the plant
      and animal genomes, as well as the rice genome.

PMID- 9576939
TI  - A Myb homologue, ATR1, activates tryptophan gene expression in Arabidopsis.
AB  - In Arabidopsis thaliana, tryptophan pathway genes are induced in response to
      starvation, wounding, and pathogen attack, resulting in increased production of
      tryptophan and secondary metabolites important for development and defense. The
      Arabidopsis tryptophan pathway therefore provides an ideal system for elucidating
      how environmental stimuli are transduced into changes in plant gene expression.
      To characterize the factors that regulate the first gene in the pathway, ASA1,
      which is the key point of control, we have isolated altered tryptophan regulation
      (atr) mutants with deregulated expression of ASA1. One of these mutants, atr1D is
      dominant for increased transcription of ASA1 in specific seedling tissues. We
      have used atr1D to clone the ATR1 gene based on its map position. ATR1 encodes a
      Myb-like transcription factor that modulates ASA1 expression. The ATR1 transcript
      also includes a 5' regulatory region with three short ORFs, one of which is
      prematurely terminated by the atr1D mutation. Thus, ATR1 defines the first
      characterized tryptophan gene regulator in plants, and the atr1D mutation defines
      a sequence important for ATR1 expression.

PMID- 9576941
TI  - Humanizing the yeast telomerase template.
AB  - Saccharomyces cerevisiae contains an irregular telomere sequence (TG1-3)n, which
      differs from the regular repeat (TTAGGG)n found at the telomeres of higher
      organisms including humans. We have modified the entire 16-nt template region of
      the S. cerevisiae telomerase RNA gene (TLC1) to produce (TTAGGG)n repeats, the
      human telomere sequence. Haploid yeast strains with the tlc1-human allele are
      viable with no growth retardation and express the humanized gene at a level
      comparable to wild type. Southern hybridization demonstrates that (TTAGGG)n
      repeats are added onto the yeast chromosome ends in haploid strains with the tlc1
      human allele, and sequencing of rescued yeast artificial chromosome ends has
      verified the addition of human telomeric repeats at the molecular level. These
      data suggest that the irregularity of the yeast telomere sequence is because of
      the template sequence of the yeast telomerase RNA. Haploid strains with the tlc1
      human allele will provide an important tool for studying the function of
      telomerase and its regulation by telomere-binding proteins, and these strains
      will serve as good hosts for human artificial chromosome assembly and
      propagation.

PMID- 9576942
TI  - Neuronal defects and delayed wound healing in mice lacking fibroblast growth
      factor 2.
AB  - Basic fibroblast growth factor (FGF2) is a wide-spectrum mitogenic, angiogenic,
      and neurotrophic factor that is expressed at low levels in many tissues and cell
      types and reaches high concentrations in brain and pituitary. FGF2 has been
      implicated in a multitude of physiological and pathological processes, including
      limb development, angiogenesis, wound healing, and tumor growth, but its
      physiological role is still unclear. To determine the function of FGF2 in vivo,
      we have generated FGF2 knockout mice, lacking all three FGF2 isoforms, by
      homologous recombination in embryonic stem cells. FGF2(-/-) mice are viable,
      fertile and phenotypically indistinguishable from FGF2(+/+) littermates by gross
      examination. However, abnormalities in the cytoarchitecture of the neocortex,
      most pronounced in the frontal motor-sensory area, can be detected by
      histological and immunohistochemical methods. A significant reduction in neuronal
      density is observed in most layers of the motor cortex in the FGF2(-/-) mice,
      with layer V being the most affected. Cell density is normal in other regions of
      the brain such as the striatum and the hippocampus. In addition, the healing of
      excisional skin wounds is delayed in mice lacking FGF2. These results indicate
      that FGF2, although not essential for embryonic development, plays a specific
      role in cortical neurogenesis and skin wound healing in mice, which, in spite of
      the apparent redundancy of FGF signaling, cannot be carried out by other FGF
      family members.

PMID- 9576943
TI  - MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the
      yeast error-free postreplication repair pathway.
AB  - Among the three Saccharomyces cerevisiae DNA repair epistasis groups, the RAD6
      group is the most complicated and least characterized, primarily because it
      consists of two separate repair pathways: an error-free postreplication repair
      pathway, and a mutagenesis pathway. The rad6 and rad18 mutants are defective in
      both pathways, and the rev3 mutant affects only the mutagenesis pathway, but a
      yeast gene that is involved only in error-free postreplication repair has not
      been reported. We cloned the MMS2 gene from a yeast genomic library by functional
      complementation of the mms2-1 mutant [Prakash, L. & Prakash, S. (1977) Genetics
      86, 33-55]. MMS2 encodes a 137-amino acid, 15.2-kDa protein with significant
      sequence homology to a conserved family of ubiquitin-conjugating (Ubc) proteins.
      However, Mms2 does not appear to possess Ubc activity. Genetic analyses indicate
      that the mms2 mutation is hypostatic to rad6 and rad18 but is synergistic with
      the rev3 mutation, and the mms2 mutant is proficient in UV-induced mutagenesis.
      These phenotypes are reminiscent of a pol30-46 mutant known to be impaired in
      postreplication repair. The mms2 mutant also displayed a REV3-dependent mutator
      phenotype, strongly suggesting that the MMS2 gene functions in the error-free
      postreplication repair pathway, parallel to the REV3 mutagenesis pathway.
      Furthermore, with respect to UV sensitivity, mms2 was found to be hypostatic to
      the rad6Delta1-9 mutation, which results in the absence of the first nine amino
      acids of Rad6. On the basis of these collective results, we propose that the mms2
      null mutation and two other allele-specific mutations, rad6Delta1-9 and pol30-46,
      define the error-free mode of DNA postreplication repair, and that these
      mutations may enhance both spontaneous and DNA damage-induced mutagenesis.

PMID- 9576944
TI  - Identification of a cAMP-dependent protein kinase catalytic subunit required for
      virulence and morphogenesis in Ustilago maydis.
AB  - Ustilago maydis, a fungal pathogen of maize, alternates between budding and
      filamentous growth in response to mating and other environmental signals. Defects
      in components of the cAMP signaling pathway affect this morphological transition
      and reveal an association of budding growth with elevated cAMP levels and
      filamentous growth with low cAMP levels. We have identified two genes, adr1 and
      uka1, encoding catalytic subunits of cAMP-dependent protein kinase (PKA).
      Disruption of adr1 resulted in a constitutively filamentous growth phenotype
      similar to that of mutants deficient in adenylyl cyclase. Importantly, adr1 is
      required for pathogenicity and is responsible for the majority of PKA activity in
      fungal cells. In contrast, uka1 has little influence on pathogenicity, and
      deletion of the uka1 gene does not affect cell morphology. These results provide
      compelling evidence that regulated PKA activity is crucial during infectious
      development of U. maydis.

PMID- 9576945
TI  - Natural killer-like nonspecific tumor cell lysis mediated by specific ligand
      activated Valpha14 NKT cells.
AB  - We have recently identified alpha-galactosylceramide (alpha-GalCer) as a specific
      ligand for an invariant Valpha14/Vbeta8.2 T cell receptor exclusively expressed
      on the majority of Valpha14 NKT cells, a novel subset of lymphocytes. Here, we
      report that alpha-GalCer selectively activates Valpha14 NKT cells resulting in
      prevention of tumor metastasis. The effector mechanisms of the ligand-activated
      Valpha14 NKT cells seem to be mediated by natural killer (NK)-like nonspecific
      cytotoxicity. Indeed, the cytotoxic index obtained by alpha-GalCer-activated
      Valpha14 NKT cells was reduced by the addition of cold target tumor cells or by
      treatment with concanamycin A, which inhibits activation and secretion of
      perforin, but not by mAbs against molecules involved in the NKT cell recognition
      and conventional cytotoxicity, such as CD1d, Vbeta8, NK1. 1, Ly49C, Fas, or Fas
      ligand. These results suggest that the ligand-activated Valpha14 NKT cells kill
      tumor cells directly through a CD1d/Valpha14 T cell receptor-independent, NK-like
      mechanism.

PMID- 9576946
TI  - Alternative splicing of rearranged T cell receptor delta sequences to the
      constant region of the alpha locus.
AB  - The T cell receptor (TCR) alpha/delta locus is composed of a common, shared set
      of variable (V) and distinct diversity (D), joining (J), and constant (C) genes.
      It has been recognized for several years that transcripts of the rearranged
      VDJdelta or VJalpha genes are spliced to the Cdelta or Calpha genes,
      respectively, encoding distinct TCR delta and alpha proteins. Herein, we describe
      the discovery of a splicing variation that allows the assembled VDJdelta genes to
      be fused with the Calpha gene. This variation is prominent in TCRdelta gene
      deficient mice but is also detectable in wild-type mice. Furthermore, we show
      that several in-frame VDJdelta rearrangements in TCRdelta gene-deficient mice are
      strikingly underrepresented, suggesting that the alternative transcripts, with
      protein coding capacity, influence the development of alphabeta thymocytes. In
      frame TCRgamma gene rearrangements do not appear underrepresented, indicating
      that the effect is not mediated by the gamma chain. Instead, indirect evidence
      supports the hypothesis that the delta/alpha chimeric protein acts in conjunction
      with the TCRbeta chain. These results have implications for the transcriptional
      control of the TCRalpha/delta locus and provide a novel insight into the distinct
      functional capacities of the TCR alpha and delta proteins during thymocyte
      development.

PMID- 9576948
TI  - Interactions with multiple peptide ligands determine the fate of developing
      thymocytes.
AB  - Thymocytes are positively or negatively selected depending on interactions
      between their T cell receptors (TCR) and peptides presented by major
      histocompatibility complex molecules. We have previously shown that apoptosis of
      thymocytes from an alpha beta TCR-transgenic mouse (F5), induced by antigenic
      peptide, can be inhibited specifically by an antagonist peptide variant in an in
      vitro culture model. We have now extended these experiments by demonstrating that
      the antagonist peptide can inhibit natural negative selection of maturing
      thymocytes, induced by endogenously expressed antigen, in fetal thymic organ
      cultures (FTOC). This inhibition resulted in the rescue and maturation of
      thymocytes that would otherwise have been deleted. Mature T cells generated in
      these cultures were able to respond to antigen by producing limited quantities of
      interferon-gamma, but unlike T cells from control FTOC, they required exogenous
      interleukin-2 to generate cytolytic effector cells. Interestingly, the antagonist
      peptide also accelerated the development of F5 thymocytes in the absence of the
      negatively selecting ligand. These data suggest that the developmental fate of a
      thymocyte may be determined by the recognition of multiple distinct peptide
      ligands during thymic selection. Alterations in the profiles of selecting
      peptides presented in the thymus would thus have profound effects on the size and
      autoreactive potential of the T cell repertoire generated.

PMID- 9576947
TI  - The mosquito Anopheles stephensi limits malaria parasite development with
      inducible synthesis of nitric oxide.
AB  - We have discovered that the mosquito Anopheles stephensi, a natural vector of
      human malaria, limits parasite development with inducible synthesis of nitric
      oxide (NO). Elevated expression of A. stephensi NO synthase (NOS), which is
      highly homologous to characterized NOS genes, was detected in the midgut and
      carcass soon after invasion of the midgut by Plasmodium. Early induction is
      likely primed by bacterial growth in the blood meal. Later increases in A.
      stephensi NOS expression and enzyme activity occurred at the beginning of
      sporozoite release. Circulating levels of nitrite/nitrate, end-products of NO
      synthesis, were significantly higher in Plasmodium-infected mosquitoes. Dietary
      provision of the NOS substrate L-arginine reduced Plasmodium infections in A.
      stephensi. In contrast, dietary provision of a NOS inhibitor significantly
      increased parasite numbers in infected mosquitoes, confirming that A. stephensi
      limits Plasmodium development with NO.

PMID- 9576949
TI  - Fibroblast growth factor receptor 1 is fused to FIM in stem-cell
      myeloproliferative disorder with t(8;13).
AB  - Chromosome 8p11-12 is the site of a recurrent breakpoint in a myeloproliferative
      disorder that involves lymphoid (T- or B-cell), myeloid hyperplasia and
      eosinophilia, and evolves toward acute leukemia. This multilineage involvement
      suggests the malignant transformation of a primitive hematopoietic stem cell. In
      this disorder, the 8p11-12 region is associated with three different partners
      6q27, 9q33, and 13q12. We describe here the molecular characterization of the
      t(8;13) translocation that involves the FGFR1 gene from 8p12, encoding a tyrosine
      kinase receptor for members of the fibroblast growth factor family, and a gene
      from 13q12, tentatively named FIM (Fused In Myeloproliferative disorders). FIM is
      related to DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1;
      this defines a gene family involved in different human pathologies. The two
      reciprocal fusion transcripts, FIM/FGFR1 and FGFR1/FIM are expressed in the
      malignant cells. The FIM/FGFR1 fusion protein contains the FIM putative zinc
      finger motifs and the catalytic domain of FGFR1. We show that it has a
      constitutive tyrosine kinase activity.

PMID- 9576950
TI  - Activation of NF-kappaB via a Src-dependent Ras-MAPK-pp90rsk pathway is required
      for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells.
AB  - Cystic fibrosis (CF) is an autosomal recessive disorder, the most common lethal
      genetic disease in Caucasians. Respiratory disease is the major cause of
      morbidity and mortality. Indeed, 95% of CF patients die of respiratory failure.
      Pseudomonas aeruginosa, an opportunistic pathogen, chronically infects the lungs
      of over 85% of CF patients. It is ineradicable by antibiotics and responsible for
      airway mucus overproduction that contributes to airway obstruction and death. The
      molecular mechanisms underlying this pathology are unknown. Here we show that P.
      aeruginosa activates a c-Src-Ras-MEK1/2-MAPK-pp90rsk signaling pathway that leads
      to activation of nuclear factor NF-kappaB (p65/p50). Activated NF-kappaB binds to
      a kappaB site in the 5'-flanking region of the MUC2 gene and activates MUC2 mucin
      transcription. These studies bring new insight into bacterial-epithelial
      interactions and more specifically into the molecular pathogenesis of cystic
      fibrosis. Understanding these signaling and gene regulatory mechanisms opens up
      new therapeutic targets for cystic fibrosis.

PMID- 9576951
TI  - Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant
      epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like
      proteases.
AB  - Alterations of the epidermal growth factor receptor (EGFR) gene occur frequently
      in human malignant gliomas. The most common of these is deletion of exons 2-7,
      resulting in truncation of the extracellular domain (DeltaEGFR or EGFRvIII),
      which occurs in a large fraction of de novo malignant gliomas (but not in
      progressive tumors or those lacking p53 function) and enhances tumorigenicity, in
      part by decreasing apoptosis through up-regulation of Bcl-XL. Here, we
      demonstrate that the DeltaEGFR concomitantly confers resistance to the
      chemotherapeutic drug cisplatin (CDDP) by suppression of CDDP-induced apoptosis.
      Expression of Bcl-XL was elevated in U87MG.DeltaEGFR cells prior to and during
      CDDP treatment, whereas it decreased considerably in CDDP-treated parental cells.
      CDDP-induced activation of caspase-3-like proteases was suppressed significantly
      in U87MG.DeltaEGFR cells. These responses were highly specific to constitutively
      kinase-active DeltaEGFR, because overexpression of kinase-deficient DeltaEGFR
      (DK) or wild-type EGFR had no such effects. Correspondingly, DeltaEGFR specific
      tyrosine kinase inhibitors reduced Bcl-XL expression and potentiated CDDP-induced
      apoptosis in U87MG.DeltaEGFR cells. Ectopic overexpression of Bcl-XL in parental
      U87MG cells also resulted in suppression of both caspase activation and apoptosis
      induced by CDDP. These results may have important clinical implications for the
      use of CDDP in the treatment of those malignant gliomas expressing DeltaEGFR.

PMID- 9576952
TI  - Chromosomal instability in the descendants of unirradiated surviving cells after
      alpha-particle irradiation.
AB  - We have demonstrated chromosomal instability in the clonal descendants of
      hemopoietic stem cells after irradiating murine bone marrow with alpha-particles.
      However, because cells that are irradiated by alpha-particles are defined by a
      Poisson distribution of individual particle traversals, there is an inevitable
      proportion of unirradiated cells in the surviving population. The calculated
      expected proportions of irradiated and nonirradiated cells indicate that the
      number of clonogenic cells transmitting chromosomal instability is greater than
      the number expected to be hit and survive. To investigate further this
      discrepancy, we studied the effects of interposing a grid between the cells and
      the alpha-particle source so that the surviving population consists predominantly
      of untraversed stem cells. Comparison with the same irradiation conditions
      without the grid reveals that the same level of instability is induced. The data
      confirm that alpha-particles induce chromosomal instability but instability is
      demonstrated in the progeny of nonirradiated stem cells and must be due to
      unexpected interactions between irradiated and nonirradiated cells. This
      untargeted effect has important implications for mechanistic studies of radiation
      action and for assessment of radiation risk.

PMID- 9576953
TI  - Genetic induction of immune tolerance to human clotting factor VIII in a mouse
      model for hemophilia A.
AB  - Patients with severe coagulation factor VIII deficiency require frequent
      infusions of human factor VIII (hFVIII) concentrates to treat life-threatening
      hemorrhages. Because these patients are immunologically hFVIII-naive, a
      significant treatment complication is the development of inhibitors or
      circulating alloantibodies against hFVIII, which bind the replaced glycoprotein,
      increase its plasma clearance, and inhibit its activity, preventing subsequent
      treatments from having a therapeutic effect. A genetic approach toward the
      induction of immunologic unresponsiveness to hFVIII has the conceptual advantage
      of a long-term, stable elimination of undesired immune responses against hFVIII.
      Here, we report that in a factor VIII (FVIII)-deficient mouse model for severe
      hemophilia A, genetic modification of donor bone marrow cells with a retroviral
      vector encoding hFVIII, and transplant to hemophiliac mouse recipients, results
      in the induction of immune tolerance to FVIII in 50% of treated animals after
      immunization with hFVIII, despite the fact that hFVIII protein or activity is
      undetectable. In tolerized animals, the titers of anti-hFVIII binding antibodies
      and of hFVIII inhibitor antibodies were significantly reduced, and there was
      evidence for hFVIII unresponsiveness in CD4(+) T cells. Importantly, the plasma
      clearance of hFVIII was significantly decreased in tolerized animals and was not
      significantly different from that seen in a FVIII-naive hemophiliac mouse. This
      model system will prove useful for the evaluation of genetic therapies for hFVIII
      immunomodulation and bring genetic therapies for hFVIII tolerance closer to
      clinical application for patients with hemophilia A.

PMID- 9576954
TI  - CCR5 coreceptor utilization involves a highly conserved arginine residue of HIV
      type 1 gp120.
AB  - The seven-transmembrane CCR5 was recently found to double as a coreceptor for a
      genetically diverse family of human and nonhuman primate lentiviruses.
      Paradoxically, the main region of the envelope protein believed to be involved in
      CCR5 utilization was mapped to hypervariable region 3, or V3, of the envelope
      glycoprotein gp120. In this study, we addressed the question of whether
      functional convergence in CCR5 utilization is mediated by certain V3 residues
      that are highly conserved among HIV type 1 (HIV-1), HIV type 2, and simian
      immunodeficiency virus. Site-directed mutagenesis carried out on three such V3
      residues revealed that the Arg-298 of HIV-1 gp120 has an important role in CCR5
      utilization. In contrast, no effect was observed for the other residues we
      tested. The inability of Arg-298 mutants to use CCR5 was not attributed to global
      alteration of gp120 conformation. Neither the expression, processing, and
      incorporation of mutant envelope proteins into virions, nor CD4 binding were
      significantly affected by the mutations. This interpretation is further supported
      by the finding that alanine substitutions of five residues immediately adjacent
      to the arginine residue had no effect on CCR5 utilization. Taken together, our
      data strongly suggests that the highly conserved Arg-298 residue identified in
      the V3 of HIV-1 has a significant role in CCR5 utilization, and may represent an
      unusually conserved target for future anti-viral designs.

PMID- 9576955
TI  - Host cell dependence of viral morphology.
AB  - The morphology of influenza virions was found to depend on cellular determinants.
      Influenza viral filaments up to 30 microm in length were observed to form at high
      levels on surfaces of various polarized epithelial cell types infected with the
      A/Udorn/72 virus. In contrast, virions produced by nonpolarized cell types
      infected with this virus were almost exclusively of spherical morphology.
      Disruption of the actin microfilament array by cytochalasin D treatment of
      polarized MDCK cells had a profound effect on viral morphology. Although virus
      titers and release of spherical particles were not reduced in the presence of
      cytochalasin D, we observed a 15-fold reduction in the release of filamentous
      particles. In contrast, the ratio of filaments to spheres produced by infected
      MDCK cells was not altered by the microtubule-disrupting agent nocodazole. These
      observations indicate that the polarized cell phenotype and the integrity of the
      actin microfilament network are important cellular determinants of the morphology
      of a filamentous influenza virus.

PMID- 9576956
TI  - A bacterial two-hybrid system based on a reconstituted signal transduction
      pathway.
AB  - We describe a bacterial two-hybrid system that allows an easy in vivo screening
      and selection of functional interactions between two proteins. This genetic test
      is based on the reconstitution, in an Escherichia coli cya strain, of a signal
      transduction pathway that takes advantage of the positive control exerted by
      cAMP. Two putative interacting proteins are genetically fused to two
      complementary fragments, T25 and T18, that constitute the catalytic domain of
      Bordetella pertussis adenylate cyclase. Association of the two-hybrid proteins
      results in functional complementation between T25 and T18 fragments and leads to
      cAMP synthesis. Cyclic AMP then triggers transcriptional activation of catabolic
      operons, such as lactose or maltose, that yield a characteristic phenotype. In
      this genetic test, the involvement of a signaling cascade offers the unique
      property that association between the hybrid proteins can be spatially separated
      from the transcriptional activation readout. This permits a versatile design of
      screening procedures either for ligands that bind to a given "bait," as in the
      classical yeast two-hybrid system, or for molecules or mutations that block a
      given interaction between two proteins of interest.

PMID- 9576957
TI  - Isolation of a hepadnavirus from the woolly monkey, a New World primate.
AB  - Hepatitis B virus (HBV) infections are a major worldwide health problem with
      chronic infections leading to cirrhosis and liver cancer. Viruses related to
      human HBV have been isolated from birds and rodents, but despite efforts to find
      hepadnaviruses that infect species intermediate in evolution between rodents and
      humans, none have been described. We recently isolated a hepadnavirus from a
      woolly monkey (Lagothrix lagotricha) that was suffering from fulminant hepatitis.
      Phylogenetic analysis of the nucleotide sequences of the core and surface genes
      indicated that the virus was distinct from the human HBV family, and because it
      is basal (ancestral) to the human monophyletic group, it probably represents a
      progenitor of the human viruses. This virus was designated woolly monkey
      hepatitis B virus (WMHBV). Analysis of woolly monkey colonies at five zoos
      indicated that WMHBV infections occurred in most of the animals at the Louisville
      zoo but not at four other zoos in the United States. The host range of WMHBV was
      examined by inoculation of one chimpanzee and two black-handed spider monkeys
      (Ateles geoffroyi), the closest nonendangered relative of the woolly monkey. The
      data suggest that spider monkeys are susceptible to infection with WMHBV and that
      minimal replication was observed in a chimpanzee. Thus, we have isolated a
      hepadnavirus with a host intermediate between humans and rodents and establishes
      a new animal model for evaluation of antiviral therapies for treating HBV chronic
      infections.

PMID- 9576958
TI  - Processing of the Ebola virus glycoprotein by the proprotein convertase furin.
AB  - In the present study, we have investigated processing and maturation of the
      envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus
      vectors was analyzed by pulse-chase experiments, the mature form and two
      different precursors were identified. First, the endoplasmic reticulum form
      preGPer, full-length GP with oligomannosidic N-glycans, was detected. preGPer
      (110 kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP
      containing mature carbohydrates. preGP was finally converted by proteolysis into
      mature GP1,2, which consisted of two disulfide-linked cleavage products, the
      amino-terminal 140-kDa fragment GP1, and the carboxyl-terminal 26-kDa fragment
      GP2. GP1,2 was also identified in Ebola virions. Studies employing site-directed
      mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located
      at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl
      chloromethylketone containing such a motif. GP is cleaved by the proprotein
      convertase furin. This was indicated by the observation that cleavage did not
      occur when GP was expressed in furin-defective LoVo cells but that it was
      restored in these cells by vector-expressed furin. The Reston subtype, which
      differs from all other Ebola viruses by its low human pathogenicity, has a
      reduced cleavability due to a mutation at the cleavage site. As a result of these
      observations, it should now be considered that proteolytic processing of GP may
      be an important determinant for the pathogenicity of Ebola virus.

PMID- 9576959
TI  - Increased calpain expression in activated glial and inflammatory cells in
      experimental allergic encephalomyelitis.
AB  - In demyelinating diseases such as multiple sclerosis (MS), myelin membrane
      structure is destabilized as myelin proteins are lost. Calcium-activated neutral
      proteinase (calpain) is believed to participate in myelin protein degradation
      because known calpain substrates [myelin basic protein (MBP); myelin-associated
      glycoprotein] are degraded in this disease. In exploring the role of calpain in
      demyelinating diseases, we examined calpain expression in Lewis rats with acute
      experimental allergic encephalomyelitis (EAE), an animal model for MS. Using
      double-immunofluorescence labeling to identify cells expressing calpain, we
      labeled rat spinal cord sections for calpain with a polyclonal millicalpain
      antibody and with mAbs for glial (GFAP, OX42, GalC) and inflammatory (CD2, ED2,
      interferon gamma) cell-specific markers. Calpain expression was increased in
      activated microglia (OX42) and infiltrating macrophages (ED2) compared with
      controls. Oligodendrocytes (galactocerebroside) and astrocytes (GFAP) had
      constitutive calpain expression in normal spinal cords whereas reactive
      astrocytes in spinal cords from animals with EAE exhibited markedly increased
      calpain levels compared with astrocytes in adjuvant controls. Oligodendrocytes in
      spinal cords from rats with EAE expressed increased calpain levels in some areas,
      but overall the increases in calpain expression were small. Most T cells in grade
      4 EAE expressed low levels of calpain, but interferon gamma-positive cells
      demonstrated markedly increased calpain expression. These findings suggest that
      increased levels of calpain in activated glial and inflammatory cells in EAE may
      contribute to myelin destruction in demyelinating diseases such as MS.

PMID- 9576960
TI  - Nitric oxide mediates N-methyl-D-aspartate receptor-induced activation of p21ras.
AB  - N-methyl-D-aspartate (NMDA) glutamate receptor-mediated increases in
      intracellular calcium are thought to play a critical role in synaptic plasticity.
      The mechanisms by which changes in cytoplasmic calcium transmit the glutamate
      signal to the nucleus, which is ultimately important for long-lasting neuronal
      responses, are poorly understood. We show that NMDA receptor stimulation leads to
      activation of p21(ras) (Ras) through generation of nitric oxide (NO) via neuronal
      NO synthase. The competitive NO synthase inhibitor, L-nitroarginine methyl ester,
      prevents Ras activation elicited by NMDA and this effect is competitively
      reversed by the NO synthase substrate, L-arginine. NMDA receptor stimulation
      fails to activate Ras in neuronal cultures from mice lacking neuronal NO
      synthase. NMDA-induced Ras activation occurs through a cGMP-independent pathway
      as 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), a potent and selective
      inhibitor of guanylyl cyclase, has no effect on NMDA receptor-induced activation
      of Ras, and the cell-permeable cGMP analog, 8Br-cGMP, does not activate Ras.
      Furthermore, NO directly activates immunoprecipitated Ras from neurons. NMDA also
      elicits tyrosine phosphorylation of extracellular signal-regulated kinases, a
      downstream effector pathway of Ras, through a NO/non-cGMP dependent mechanism,
      thus supporting the physiologic relevance of endogenous NO regulation of Ras.
      These results suggest that Ras is a physiologic target of endogenously produced
      NO and indicates a signaling pathway for NMDA receptor activation that may be
      important for long-lasting neuronal responses.

PMID- 9576961
TI  - Neurotrophins inhibit major histocompatibility class II inducibility of
      microglia: involvement of the p75 neurotrophin receptor.
AB  - Major histocompatibility complex (MHC) molecules are rare in the healthy brain
      tissue, but are heavily expressed on microglial cells after inflammatory or
      neurodegenerative processes. We studied the conditions leading to the induction
      of MHC class II molecules in microglia by using explant cultures of neonatal rat
      hippocampus, a model of interacting neuronal networks. Interferon-gamma (IFN
      gamma)-dependent MHC class II inducibility in microglia cells was very low, but
      strongly increased in the hippocampal slices after the blockade of neuronal
      activity by neurotoxins [tetrodotoxin (TTX), omega-conotoxin] or glutamate
      antagonists. None of these agents acted directly on isolated microglia cells. We
      found that neurotrophins modulate microglial MHC class II expression. MHC class
      II inducibility was enhanced by neutralization of neurotrophins produced locally
      within the cultured tissues and was inhibited by the addition of nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF), or neurotrophin-3 (NT3).
      NGF and, to a lower extent, NT3 acted directly on isolated microglia via the p75
      neurotrophin receptor and inhibited MHC class II inducibility as shown by
      blockade of the p75 neurotrophin receptor with antibodies. Our data suggest that
      neurotrophins secreted by electrically active neurons control the antigen
      presenting potential of microglia cells, and indicate that this effect is
      mediated partly via the p75 neurotrophin receptor.

PMID- 9576962
TI  - Alleviation of x-irradiation-based deficit in memory-based learning by D
      amphetamine: suggestions for attention deficit-hyperactivity disorder.
AB  - Selective exposure to x-irradiation during infancy, from postnatal days (PND) 2
      11 in the rat, results in severe hippocampal granule cell hypoplasia. Preweanling
      (PND 17-18) rats, which suffer such hippocampal granule-cell agenesis, show
      deficits in patterned single alternation (PSA), a form of memory-based learning.
      Deficits in short-term memory along with increased arousal have been suggested as
      characteristic of children diagnosed with attention deficit-hyperactivity
      disorder (ADHD). We report here on the ameliorating effects of D-amphetamine, a
      drug commonly used in the treatment of ADHD, before Ritalin, on PSA, after
      infantile (PND 2-15) exposure to x-irradiation. After i.p. injections of 0.3
      mg/kg D-amphetamine, the onset and magnitude of the PSA memory-based
      discrimination in the x-irradiated preweanling rats was restored to about the
      level of controls. These results, showing alleviation of x-irradiation-related
      deficits in short-term memory by D-amphetamine injections, along with our earlier
      and present results, showing substantial deficits after x-irradiation alone,
      encourage the hypothesis that hippocampal granule-cell hypoplasia, which would
      occur in humans prenatally and is Altman's model of "minimal brain dysfunction"
      [Altman, J. (1986) in Learning Disabilities and Prenatal Risk, ed. Lewis, M.
      (Univ. of Illinois Press, Urbana), pp. 241-304], may be a factor in at least some
      forms of ADHD and may provide a basis for an animal model of the disease.

PMID- 9576963
TI  - Transgenic mice expressing human Bcl-2 in their neurons are resistant to 6
      hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine neurotoxicity.
AB  - The protooncogene bcl-2 inhibits neuronal apoptosis during normal brain
      development as well as that induced by cytotoxic drugs or growth factor
      deprivation. We have previously demonstrated that neurons of mice deficient in
      Bcl-2 are more susceptible to neurotoxins and that the dopamine (DA) level in the
      striatum after systemic 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)
      administration was significantly lower than in wild-type mice. In the present
      study we have used transgenic mice overexpressing human Bcl-2 under the control
      of neuron-specific enolase promoter (NSE-hbcl-2) to test the effects of the
      neurotoxins 6-hydroxydopamine (6-OHDA) and MPTP on neuronal survival in these
      mice. Primary cultures of neocortical neurons from normal and transgenic mice
      were exposed to these dopaminergic neurotoxins. Addition of 6-OHDA resulted in
      cell death of essentially all neurons from normal mice. In contrast, in cultures
      generated from heterozygous NSE-hbcl-2 transgenic mice, only 69% of the cells
      died while those generated from homozygous transgenic mice were highly resistant
      and exhibited only 34% cell death. A similar effect was observed with neurons
      treated with MPP+. Moreover, while the striatal dopamine level after MPTP
      injections was reduced by 32% in the wild type, the concentration remained
      unchanged in the NSE-hbcl-2 heterozygous mice. In contrast levels of glutathione
      related enzymes were unchanged. In conclusion, overexpression of Bcl-2 in the
      neurons provided protection, in a dose-dependent manner, against neurotoxins
      known to selectively damage dopaminergic neurons. This study provides ideas for
      inhibition of neuronal cell death in neurodegenerative diseases and for the
      development of efficient neuroprotective gene therapy.

PMID- 9576964
TI  - Amyloid beta-peptide stimulates nitric oxide production in astrocytes through an
      NFkappaB-dependent mechanism.
AB  - The major pathological features of Alzheimer's disease (AD) include amyloid
      plaques composed primarily of the beta-amyloid (Abeta) peptide, degenerating
      neurons and neurofibrillary tangles, and the presence of numerous activated
      astrocytes and microglia. Although extensive genetic data implicate Abeta in the
      neurodegenerative cascade of AD, the molecular mechanisms underlying its effects
      on neurons and glia and the relationship between glial activation and neuronal
      death are not well defined. Abeta has been shown to induce glial activation, and
      a growing body of evidence suggests that activated glia contribute to
      neurotoxicity through generation of inflammatory cytokines and neurotoxic free
      radicals, such as nitric oxide (NO), potent sources of oxidative stress known to
      occur in AD. It is therefore crucial to identify specific Abeta-induced molecular
      pathways mediating these responses in activated glia. We report that Abeta
      stimulates the activation of the transcription factor NFkappaB in rat astrocytes,
      that NFkappaB activation occurs selectively from p65 transactivation domain 2,
      and that Abeta-induced NO synthase expression and NO production occur through an
      NFkappaB-dependent mechanism. This demonstration of how Abeta couples an
      intracellular signal transduction pathway involving NFkappaB to a potentially
      neurotoxic response provides a key mechanistic link between Abeta and the
      generation of oxidative damage. Our results also suggest possible molecular
      targets upon which to focus future drug discovery efforts for AD.

PMID- 9576965
TI  - GFRalpha3 is an orphan member of the GDNF/neurturin/persephin receptor family.
AB  - GDNF, neurturin, and persephin are transforming growth factor beta-related
      neurotrophic factors known collectively as the GDNF family (GF). GDNF and
      neurturin signal through a multicomponent receptor complex containing a signaling
      component (the Ret receptor tyrosine kinase) and either of two glycosyl
      phosphatidylinositol-linked binding components (GDNF family receptor alpha
      components 1 and 2, GFRalpha1 or GFRalpha2), whereas the receptor for persephin
      is unknown. Herein we describe a third member of the GF coreceptor family called
      GFRalpha3 that is encoded by a gene located on human chromosome 5q31.2-32.
      GFRalpha3 is not expressed in the central nervous system of the developing or
      adult animal but is highly expressed in several developing and adult sensory and
      sympathetic ganglia of the peripheral nervous system. GFRalpha3 is also expressed
      at high levels in developing, but not adult, peripheral nerve. GFRalpha3 is a
      glycoprotein that is glycosyl-phosphatidylinositol-linked to the cell surface
      like GFRalpha1 and GFRalpha2. Fibroblasts expressing Ret and GFRalpha3 do not
      respond to any of the known members of the GDNF family, suggesting that GFRalpha3
      interacts with an unknown ligand or requires a different or additional signaling
      protein to function.

PMID- 9576966
TI  - Morphine disrupts long-range synchrony of gamma oscillations in hippocampal
      slices.
AB  - Oscillations in neuronal population activity within the gamma frequency band (>25
      Hz) have been correlated with cognition: Gamma oscillations could bind together
      features of a sensory stimulus by generating synchrony between discrete cortical
      areas [Eckhorn, R., Bauer, R., Jordan, W., Brosch, M., Kruse, W., Munk, M. &
      Reitboeck, H. J. (1989) Biol. Cybern. 60, 121-130; Singer, W. & Gray, C. M.
      (1995) Annu. Rev. Neurosci. 18, 555-556]. Herein we demonstrate that morphine and
      beta-endorphin disrupt this long-range synchrony of gamma oscillations while
      leaving the synchrony of local oscillations relatively intact. The effect is
      caused by a decrease in type A gamma-aminobutyric acid receptor-mediated
      inhibition of both excitatory pyramidal cells and inhibitory interneurons. The
      effects of morphine on gamma oscillations were blocked by mu-opioid receptor
      antagonists but not by antagonists of delta or kappa receptors. Morphine also
      produced burst firing in interneurons, because synaptic excitation from pyramidal
      cells was no longer balanced by synchronous inhibitory postsynaptic potentials.
      The loss of synchrony of gamma oscillations induced by morphine may constitute
      one mechanism involved in producing the cognitive deficits that this drug causes
      clinically.

PMID- 9576967
TI  - ETR2 is an ETR1-like gene involved in ethylene signaling in Arabidopsis.
AB  - The plant hormone ethylene regulates a variety of processes of growth and
      development. To identify components in the ethylene signal transduction pathway,
      we screened for ethylene-insensitive mutants in Arabidopsis thaliana and isolated
      a dominant etr2-1 mutant. The etr2-1 mutation confers ethylene insensitivity in
      several processes, including etiolated seedling elongation, leaf expansion, and
      leaf senescence. Double mutant analysis indicates that ETR2 acts upstream of
      CTR1, which codes for a Raf-related protein kinase. We cloned the ETR2 gene on
      the basis of its map position, and we found that it exhibits sequence homology to
      the ethylene receptor gene ETR1 and the ETR1-like ERS gene. ETR2 may thus encode
      a third ethylene receptor in Arabidopsis, transducing the hormonal signal through
      its "two-component" structure. Expression studies show that ETR2 is ubiquitously
      expressed and has a higher expression in some tissues, including inflorescence
      and floral meristems, petals, and ovules.

PMID- 9576968
TI  - Defense activation and enhanced pathogen tolerance induced by H2O2 in transgenic
      tobacco.
AB  - Transgenic tobacco deficient in the H2O2-removing enzyme catalase (Cat1AS) was
      used as an inducible and noninvasive system to study the role of H2O2 as an
      activator of pathogenesis-related (PR) proteins in plants. Excess H2O2 in Cat1AS
      plants was generated by simply increasing light intensities. Sustained exposure
      of Cat1AS plants to excess H2O2 provoked tissue damage, stimulated salicylic acid
      and ethylene production, and induced the expression of acidic and basic PR
      proteins with a timing and magnitude similar to the hypersensitive response
      against pathogens. Salicylic acid production was biphasic, and the first peak of
      salicylic acid as well as the peak of ethylene occurred within the first hours of
      high light, which is long before the development of tissue necrosis. Under these
      conditions, accumulation of acidic PR proteins was also seen in upper leaves that
      were not exposed to high light, indicating systemic induction of expression.
      Short exposure of Cat1AS plants to excess H2O2 did not cause damage, induced
      local expression of acidic and basic PR proteins, and enhanced pathogen
      tolerance. However, the timing and magnitude of PR protein induction was in this
      case more similar to that in upper uninfected leaves than to that in
      hypersensitive-response leaves of pathogen-infected plants. Together, these data
      demonstrate that sublethal levels of H2O2 activate expression of acidic and basic
      PR proteins and lead to enhanced pathogen tolerance. However, rapid and strong
      activation of PR protein expression, as seen during the hypersensitive response,
      occurs only when excess H2O2 is accompanied by leaf necrosis.

PMID- 9576969
TI  - DNA methylation and the promotion of flowering by vernalization.
AB  - We have tested the hypothesis that the promotion of flowering by prolonged
      exposure to low temperatures (vernalization) is mediated by DNA demethylation
      [Burn, J. E., Bagnall, D. J., Metzger, J. M., Dennis, E. S. & Peacock, W. J.
      (1993) Proc. Natl. Acad. Sci. USA 90, 287-291]. Arabidopsis plants that have
      reduced levels of DNA methylation because of the presence of a methyltransferase
      (METI) antisense gene flowered earlier than untransformed control plants, without
      the need for a cold treatment. Decreased DNA methylation mutants (ddm1) also
      flowered earlier than the wild-type progenitor under conditions where they
      respond to vernalization. We conclude that demethylation of DNA is sufficient to
      cause early flowering, and we have found that the promotion of flowering is
      directly proportional to the decrease in methylation in METI antisense lines. The
      early-flowering phenotype was inherited in sexual progeny, even when the
      antisense transgene had been lost by segregation. Methyltransferase antisense
      plants with low DNA methylation levels responded to a low-temperature treatment
      by flowering even earlier than their untreated siblings indicating that the
      promotion of flowering by cold and by demethylation was additive when neither
      treatment saturated the early-flowering response. As in untransformed control
      plants, the cold-induced early-flowering signal was reset in progeny of METI
      antisense plants. These observations suggest that the demethylation brought about
      by a METI antisense can account for some properties of vernalization, but not for
      the need for revernalization in each generation.

PMID- 9576971
TI  - Locomotion and body proportions of the Saint-Cesaire 1 Chatelperronian
      Neandertal.
AB  - The initial Upper Paleolithic (Chatelperronian) of western Europe was associated
      with late European Neandertals, best known through the Saint-Cesaire 1 partial
      skeleton. Biomechanical cross-sectional analysis of the Saint-Cesaire 1 femoral
      diaphysis at the subtrochanteric and midshaft levels, given the plasticity of
      mammalian diaphyseal cortical bone, provides insights into the habitual levels
      and patterns of loading on the lower limbs from body mass, proportions, and
      locomotion. The overall robustnesses of the femoral diaphyses of European
      Neandertals and early modern humans are similar once contrasts in body
      proportions are incorporated into the body size scaling. Saint-Cesaire 1 matches
      these samples only if it is provided with Neandertal-like hyperarctic body
      proportions. And the rounded proximal femoral diaphysis of Saint-Cesaire 1 is
      similar to those of earlier Neandertals, likely also reflecting similar cold
      adapted broad pelvic regions. However, although morphologically similar to those
      of archaic Homo, the Saint-Cesaire 1 femoral midshaft exhibits the
      anteroposterior reinforcement characteristic of early modern humans.
      Consequently, Saint-Cesaire 1 appears as a morphological Neandertal with
      hyperarctic body proportions who nonetheless had shifted locomotor patterns to
      more closely resemble those of other Upper Paleolithic humans.

PMID- 9576970
TI  - Chlorophyll a availability affects psbA translation and D1 precursor processing
      in vivo in Synechocystis sp. PCC 6803.
AB  - Transcript accumulation and translation of psbA as well as processing of the D1
      precursor protein were investigated in relation to chlorophyll availability in
      vivo in cyanobacterial strains lacking photosystem I (PS I). The psbA transcript
      level was almost independent of chlorophyll availability and was approximately 3
      fold lower in darkness than in continuous light (5 microE m-2 s-1). Upon
      illumination, it reached a steady-state level within several hours. Upon growth
      under light-activated heterotrophic growth conditions (LAHG) in the PS I-less
      strain, D1 synthesis occurred immediately upon illumination. However, in PS I
      less/chlL- cells, which lacked the light-independent chlorophyll biosynthesis
      pathway and had very low chlorophyll levels after LAHG growth, very little D1
      synthesis occurred upon illumination, and the synthesis rate increased with time.
      This result suggests a translational control of D1 biosynthesis related to
      chlorophyll availability. Upon illumination, initially a high level of the
      nonprocessed D1 precursor was observed by pulse labeling and immunodetection in
      LAHG-grown PS I-less/chlL- cells but not in PS I-less cells. A significant amount
      of the D1 precursor eventually was processed to mature D1, and the half-life of
      the D1 precursor decreased as the chlorophyll content of the cells increased. The
      D1 processing enzyme CtpA was found to be present at similar levels regardless
      illumination or chlorophyll levels. We conclude that, directly or indirectly,
      chlorophyll availability is needed for D1 translation as well as for efficient
      processing of the D1 precursor.

PMID- 9576972
TI  - Is parathyroid hormone a therapeutic option for osteoporosis? A review of the
      clinical evidence.
AB  - Most of the data on the anabolic effect of PTH have been obtained with hPTH(1
      34). Studies have shown a marked increment in spinal bone mass. Most recently we
      have shown that PTH and estrogen can be given together where there is increased
      total bone mineral and no loss of bone at any skeletal site. We have also shown
      the first reduction in vertebral deformity incidence due to PTH treatment.

PMID- 9576974
TI  - Relationship between spine bone mineral density and vertebral body heights.
AB  - The aim of this study was to investigate the correlation between lumbar spine
      bone mineral density (LS-BMD) and the vertebral body heights with advancing age
      and years since menopause. One hundred and sixty-three women ages 39-74 years (77
      normal premenopausal, ages 39-54, and 86 normal postmenopausal, ages 46-74 years)
      were studied. LS-BMD was measured by dual energy X-ray absorptiometry. Vertebral
      heights were evaluated, using morphometry, as the sum of anterior (AHs), middle
      (MHs), and posterior (PHs) vertebral body heights from T4 to L5. The AHs/PHs
      ratio at the same level was also calculated. AHs, MHs, PHs, and AHs/PHs ratio
      directly correlated with LS-BMD; the correlations are AHs r = 0.80, P < 0.0001,
      MHs r = 0.75, P < 0.0001, PHs r = 0.76, P < 0.0001, and AHs/PHs r = 0.66, P <
      0.001. Both LS-BMD and AHs are inversely correlated with age, and the regressions
      fit with both linear and cubic curves. The statistical significance of the
      correlations persists while maintaining age constant. The linear regression curve
      of AHs with age indicates that the spine height decrement rate is 2.12 mm/year,
      corresponding to 7.4 cm in 35 years. AHs decreases immediately after menopause
      fitting with a cubic curve model, with a decrement rate of about 3 cm in the
      first 5 years after menopause. We conclude that the measurement of the sum of
      vertebral body heights could usefully integrate LS-BMD evaluation in the clinical
      and epidemiological investigation of osteoporosis.

PMID- 9576973
TI  - Discordance between ultrasound of the calcaneus and bone mineral density in black
      and white women.
AB  - Black women have 40% of the incidence rate for hip fracture and have a higher
      bone mineral density (BMD) than white women. The possibility was raised that bone
      quality may be disproportionately greater than the advantage in bone density in
      protection against osteoporotic fractures in black versus white women. Ultrasound
      (US) of the calcaneus is believed to measure properties of bone in addition to
      its density. We performed bone density measurements and US of the calcaneus in
      108 black and 177 healthy white women, aged 20-70 years. The highest correlation
      was seen between total body bone density and speed of sound (r = 0.75). The
      interracial differences in BMD were all statistically significant and varied from
      3.4 to 7.6%. The US measurements had lesser interracial differences than the bone
      density measurements, with velocity barely different between races. These
      findings suggest that US of the calcaneus measures properties of bone different
      from density. Fracture prediction data using US from prospective data in white
      women should not be extrapolated to black women because of the discordance
      between bone density and US measurements. Prospective studies are needed
      comparing US measurements in black women to the occurrence of osteoporotic
      fractures.

PMID- 9576976
TI  - High thigh muscle strength but not bone mass in young horseback-riding females.
AB  - To evaluate whether the type of weight-bearing loading subjected to the skeleton
      during horseback-riding was associated with differences in bone mass and muscle
      strength of the thigh, we investigated bone mass and isokinetic muscle strength
      in 20 female horse riders (age 17.9 +/- 0.6 years) who were riding 7.0 +/- 3.4
      hours/week, and 20 nonactive females (age 17.8 +/- 1.1 years). The groups were
      matched according to age, weight, and height. Areal bone mineral density was
      measured in total body, head, lumbar spine, right femoral neck, Ward's triangle,
      and trochanter, the whole dominant and nondominant humerus, and in specific sites
      in the right femur diaphysis, distal femur, proximal tibia, and tibia diaphysis
      using dual X-ray absorptiometry. Isokinetic concentric and eccentric peak torque
      of the quadricep and hamstring muscles were measured using an isokinetic
      dynamometer. There were no significant differences in bone mass between the
      horseback riders and nonactives at any site measured. The horse riders were
      significantly (P < 0.05-0.01) stronger in concentric hamstrings strength at 90
      degrees/second and 225 degrees/second and in eccentric quadricep and hamstring
      strength at 90 degrees/second. Horseback riding in young females is associated
      with a high muscle strength of the thigh, but not with a high bone mass.

PMID- 9576975
TI  - Bone mineral content and density in professional tennis players.
AB  - Total and regional bone mineral content (BMC) as well as lean and fat mass were
      measured in nine male professional tennis players (TPs) and 17 nonactive
      subjects; dual-energy X-ray absorptiometry (DXA) was used for measuring. The mean
      (+/-SD) age, body mass, and height were 26 +/- 6 and 24 +/- 3 years, 77 +/- 10
      and 74 +/- 9 kg, and 180 +/- 6 and 178 +/- 6 cm for the TP and the control group
      (CG), respectively. The whole body composition for BMC, lean mass, and fat of the
      TP was similar to that observed in the CG. The tissue composition of the arms and
      legs was determined from the regional analysis of the whole-body DXA scan. The
      arm region included the hand, forearm, and arm, and was separated from the trunk
      by an inclined line crossing the scapulo-humeral joint. In the TP, the arm tissue
      mass (BMC + fat + lean mass) was about 20% greater in the dominant compared with
      the contralateral arm because of a greater lean (3772 +/- 500 versus 3148 +/- 380
      g, P < 0.001) and BMC (229.0 +/- 43.5 versus 188.2 +/- 31.9 g, P < 0.001). In
      contrast, no significant differences were observed either in BMC or BMD between
      arms in the CG. Total mass, lean mass, and BMC were greater in the dominant arm
      of the TP than in the CG (all P < 0.05). In the TP, BMD was similar in both legs
      whereas in the CG, BMD was greater in the right leg. Lumbar spine (L2-L4) BMD,
      adjusted for body mass and height, was 15% greater in the TP than in the CG (P <
      0.05). Femoral neck BMDs (femoral neck, Ward's triangle, greater trochanter, and
      intertrochanteric regions) adjusted for body mass and height were 10-15% greater
      in the TP (all P < 0.05). Ward's triangle BMD was correlated with the maximal leg
      extension isometric strength (r = 0. 77, P < 0.05) even when adjusted for body
      mass (r = 0.76, P < 0.05) and height (r = 0.77, P < 0.05). In summary, the
      participation in tennis is associated with increased BMD in the lumbar spine and
      femoral neck. These results may have implications for devising exercise
      strategies in young and middle-aged persons to prevent involutional osteoporosis
      later in life.

PMID- 9576977
TI  - The less potent estrogenic effect of tamoxifen on bone in ovariectomized rats
      with established osteopenia.
AB  - The longitudinal effects of tamoxifen (TAM) treatment on bone metabolism, spinal
      bone mineral density (BMD), and bone mineral content (BMC) were compared with
      those of estrogen in ovariectomized (OVX) rats with established osteopenia. The 6
      month-old rats were divided into Sham (n = 8) and OVX (n = 24) groups. First, the
      OVX rats were allowed to lose bone for 6 weeks. Six weeks after ovariectomy they
      were divided into three groups: (1) OVX rats treated with solvent vehicle
      (OVX+Vehicle), (2) OVX rats injected with TAM subcutaneously six times a week at
      a dosage of 1.0 mg/kg body weight (OVX+TAM), (3) OVX rats injected with 17-beta
      estradiol subcutaneously six times a week at a dosage of 0.1 mg/kg body weight
      (OVX+ET). The longitudinal effects of TAM and estrogen on bone were studied by
      dual energy X-ray absorptiometry (DXA) and biochemical markers including urinary
      pyridinoline (Pyr) and deoxypyridinoline (Dpyr). Ovariectomy resulted in a
      significant increase in urinary Pyr, Dpyr, and a significant decrease in spine
      BMD and BMC. TAM treatment completely inhibited the further bone loss in OVX rats
      with established osteopenia, however, estrogen increased spine BMD and BMC
      significantly compared with OVX+Vehicle, OVX+TAM, and baseline of treatment. Both
      TAM and estrogen treatment decreased urinary Pyr and Dpyr significantly in OVX
      rats. Our findings indicate that TAM acts as an estrogen agonist with respect to
      effects on spine BMD, BMC, and bone resorption in OVX rats with established
      osteopenia, but fails to restore spine BMD and BMC to the extent observed with
      estrogen in this study.

PMID- 9576978
TI  - Estrogen and cancellous bone loss in the fowl.
AB  - Female birds model a type of woven bone prior to egg laying which is known as
      medullary bone. Medullary bone modeling is estrogen dependent and in the female
      fowl coincides with a decrease in cancellous bone volume. Medullary bone modeling
      was induced in male laying-strain fowl by the administration of estrogen and
      prevented in females by the administration of tamoxifen. In estrogen-treated
      males, medullary bone modeling was accompanied by cancellous bone loss;
      cancellous bone volume was significantly lower than in control males (P < 0.001).
      In females, the prevention of medullary bone modeling by tamoxifen treatment
      resulted in significantly higher cancellous bone volumes than in control females
      (P < 0.001). Estrogen therefore appears to play a role in cancellous bone loss in
      the fowl.

PMID- 9576979
TI  - Evaluation of bone mineral density using three-dimensional solid state phosphorus
      31 NMR projection imaging.
AB  - A solid state magnetic resonance imaging technique is used to measure true three
      dimensional mineral density of synthetic hydroxyapatite phantoms and specimens of
      bone ex vivo. The phosphorus-31 free induction decay at 2.0 T magnetic field
      strength is sampled following application of a short, hard radiofrequency
      excitation pulse in the presence of a fixed amplitude magnetic field gradient.
      Multiple gradient directions covering the unit sphere are used in an efficient
      spherical polar to Cartesian interpolation and Fourier transform projection
      reconstruction scheme to image the three-dimensional distribution of phosphorus
      within the specimen. Using 3-6 Gauss/cm magnetic field gradients, a spatial
      resolution of 0.2 cm over a field of view of 10 cm is achieved in an imaging time
      of 20-35 minutes. Comparison of solid state magnetic resonance imaging with dual
      energy X-ray absorptiometry (DXA), gravimetric analysis, and chemical analysis of
      calcium and phosphorus demonstrates good quantitative accuracy. Direct
      measurement of bone mineral by solid state magnetic resonance opens up the
      possibility of imaging variations in mineral composition as well as density.
      Advantages of the solid state magnetic resonance technique include avoidance of
      ionizing radiation; direct measurement of a constituent of the mineral without
      reliance on assumptions about, or models of, tissue composition; the absence of
      shielding, beam hardening, or multiple scattering artifacts; and its three
      dimensional character. Disadvantages include longer measurement times and lower
      spatial resolution than DXA and computed tomography, and the inability to scan
      large areas of the body in a single measurement, although spatial resolution is
      sufficient to resolve cortical from trabecular bone for the purpose of measuring
      bone mineral density.

PMID- 9576980
TI  - Modulation of bone mass, strength, and turnover by a new benzamide compound, DU
      6712, in adjuvant-induced arthritic rats.
AB  - To assess the reductions in bone mass, strength, and turnover in adjuvant-induced
      arthritic rats and to examine the effect of a new benzamide compound, DU-6712, on
      these parameters, a 28-day dosing experiment was performed using 8-week-old
      female Lewis rats. Arthritis was induced by injecting the adjuvant into the hind
      paw. The age-dependent increases in the body weight, lumbar bone mineral content
      and density (BMC and BMD) and compressive strength were disturbed in the
      arthritic rats. At 14 days, the histomorphometric parameters of bone formation
      (BFR/BS and BFR/BV) and the serum osteocalcin levels were significantly reduced
      compared with the baseline controls. However, the BMC values corrected for body
      weight did not differ significantly between the arthritic and normal rats, and
      the bone minerals were not reduced compared with the baseline controls. At 28
      days, the parameters of bone minerals and strength of the lumbar body in the
      arthritic rats, both with and without correction for body weight, were
      significantly reduced compared with the baseline controls. The trabecular
      mineralizing surface remained significantly reduced and the osteoclast numbers
      were increased. DU-6712 at the doses of 5, 15, and 45 mg/kg, orally administered
      daily from the start of the experiment, significantly prevented the development
      of the chronic paw edema at 28 days. The reductions in the parameters of bone
      minerals, strength, and trabecular bone formation, and the increase in osteoclast
      number were alleviated by this agent. Age-dependent increases in the lumbar
      height, disturbed by the adjuvant injection, were also maintained. These data
      indicated that a 28-day period is necessary to obtain sufficient reductions in
      the bone mass and strength of the lumbar body concerning the model of secondary
      osteoporosis in adjuvant arthritic rats. DU-6712 was able to prevent these
      reductions by modulating the bone turnover in this arthritis model.

PMID- 9576981
TI  - Human osteoclast formation from blood monocytes, peritoneal macrophages, and bone
      marrow cells.
AB  - Mononuclear precursors of the human osteoclast have been identified in both bone
      marrow and the circulation in man, but osteoclast membership of the mononuclear
      phagocyte system (MPS) and its precise cellular ontogeny remain controversial. We
      isolated human hematopoietic marrow cells, blood monocytes, and peritoneal
      macrophages and incubated each of these cell populations with UMR106 osteoblast
      like cells on glass coverslips and dentine slices in both the presence and
      absence of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), macrophage-colony stimulating
      factor (M-CSF), and dexamethasone. Cells isolated from peripheral blood and
      peritoneal dialysis fluid were positive only for monocyte/macrophage markers
      (CD11a, CD11b, CD14, and HLA-DR) and negative for osteoclast markers [tartrate
      resistant acid phosphatase (TRAP), vitronectin reception (VNR), and calcitonin
      (CT) receptors and did not form resorption pits on dentine slices after 24 hours
      in culture. Similarly marrow cells did not form resorption pits on dentine slices
      after 24 hours in culture. However, after 14 days in co-culture with UMR106
      cells, in the presence of 1,25(OH)2D3 and M-CSF, numerous TRAP, CT receptor, and
      VNR-positive multinucleated cells capable of extensive lacunar resorption were
      formed in co-cultures of all these preparations. The presence of 1,25 (OH)2D3, M
      CSF, and UMR106 were absolute requirements for osteoclast differentiation. It is
      concluded that precursor cells capable of osteoclast differentiation are present
      in the marrow compartment, the monocyte fraction of peripheral blood, and in the
      macrophage compartment of extraskeletal tissues and that these cells are capable
      of differentiating into mature functional osteoclasts. These findings argue in
      favor of osteoclast membership of the human MPS.

PMID- 9576982
TI  - Age-related changes in the expression of cadherin-11, the mesenchyme specific
      calcium-dependent cell adhesion molecule.
AB  - Cadherin-11 is a calcium-dependent cell adhesion molecule that is expressed in
      cells of the mesenchymal lineage during embryonic development. In this study we
      show, for the first time, that cadherin-11 gene is expressed in the bone marrow
      and bone cells obtained from rabbits of various age groups. Furthermore, a
      quantitative measurement of gene expression revealed that cadherin-11 was
      expressed in young rabbits (6 week-old: open epiphysis) at a level of 6.7 x 10(5)
      +/- 0.7 x 10(5) molecules; in mature rabbits (8-10 month-old: closed epiphysis)
      at 11 x 10(5) +/- 0.9 x 10(5) molecules; and in aged rabbits (4-5 year-old) at a
      level of 1.2 x 10(5) +/- 0.2 x 10(5) molecules/microg total RNA. The relative
      level of cadherin-11 gene expression in mature rabbit marrow was found to be
      approximately 50% greater than in young rabbits. However, aged animals showed a
      reduction in cadherin-11 specific gene expression of greater than 900% as
      compared with mature animals. Age-related changes in bone remodeling/turnover
      lead to reduced bone density and high fracture risk, and since cadherins play a
      crucial role in tissue morphogenesis, this marked decrease may represent an index
      of the aging process in bone.

PMID- 9576983
TI  - Usefulness of ultrasound in Sudeck's atrophy of the foot.
AB  - Quantitative ultrasound (QUS) of bone has been proposed as an inexpensive and
      radiation-free device method of assessing skeletal status. QUS has been widely
      used in the assessment of osteoporosis. Until now only few data are available on
      the usefulness of QUS in different disorders, such as Sudeck's atrophy. To
      evaluate the ability of QUS in the diagnosis and monitoring of regional
      osteoporosis, we investigated 19 patients (12 women and 7 men, age range 30-65
      years) with osteoporosis of the foot (Sudeck's atrophy), as evidenced by X-ray
      study and Technetium-99 bone scan. In all patients we measured speed of sound
      (SOS), broadband ultrasound attenuation (BUA), and stiffness of the calcaneus
      using Lunar Achilles Ultrasound, both in the affected and unaffected foot. Bone
      mineral density at the lumbar spine, by DXA (Hologic QDR 1000), was also
      performed. QUS was repeated after 3 and 6 months of treatment with salmon
      calcitonin (100 IU I.M. every second day). At baseline, SOS, BUA, and stiffness,
      expressed as T-score, were -1.9, -2.4, and -2.4 in unaffected feet and -2.9, 
      5.1, and -4.3, respectively, in affected feet. The difference between the
      unaffected and affected foot was significant for SOS, BUA, and stiffness (P <
      0.001). No significant difference was found in QUS parameters in the unaffected
      foot during the study period. After 3 and 6 months of treatment, SOS increased in
      the affected foot by 0.2% and 0.3%, BUA increased by 6. 2% and 8.2%, and
      stiffness by 7.5% and 11.1%, respectively. In conclusion, BUA and stiffness seem
      to be influenced more than SOS by Sudeck's atrophy; QUS, namely, BUA and
      stiffness, significantly increase with calcitonin treatment. In conclusion, QUS
      is a sensitive tool in the diagnosis of Sudeck's atrophy of the foot and is
      adequate for measuring improvement in bone status following treatment.

PMID- 9576984
TI  - Hip fracture epidemiology in Greece during 1977-1992.
AB  - Hip fracture, the most dramatic complication of osteoporosis, constitutes a
      serious health problem of the elderly, with great socioeconomic consequences. Hip
      fracture epidemiology has been studied by many investigators. Until now, reported
      studies in Greece include either data from only one region, or they do not
      include all the epidemiological parameters concerning hip fractures. We studied
      hip fractures that occurred in Greece in 1992 and compared the findings with
      those of previous years (1977, 1982, 1987), in order to identify age and sex
      incidence and increase rate during 1977-1992. There has been an average annual
      increase of 7.6%, thus total hip fractures in Greece increased from 5,100 in 1977
      (54.75 fractures/100,000 inhabitants) to 10,953 in 1992 (107.30 fractures/100,000
      inhabitants). In 1992, 70% of the patients were women. During the 1977-1992
      period, age-adjusted incidence for people aged over 50 increased in both sexes
      (from 173.54 fractures/100,000 inhabitants in 1977 to 314.07 fractures/100,000
      inhabitants in 1992, an increase of age-adjusted incidence of 80. 97%).
      Approximately 50% of the patients in 1992 were aged 80 and over, whereas in 1977
      there were only 22.49% patients of the same age. The increase in hip fracture
      numbers is greater than expected due to population aging, suggesting the
      existence of other factors influencing this increase. The most affected age group
      is 80 and over.

PMID- 9576986
TI  - Effect of benidipine hydrochloride, a dihydropyridine-type calcium antagonist, on
      the function of mouse osteoblastic cells.
AB  - The effects of benidipine hydrochloride (BD), a dihydropyridine-type calcium
      antagonist, on the growth and alkaline phosphatase (ALPase) activity were studied
      in cultures of mouse osteoblastic cells. BD (0.1-10 nM) increased the ALPase
      activity of osteoblastic cells and reduced cell proliferation incubated for 48 h.
      This reduction of cell growth did not appear to be due to cell death. On the
      other hand, nifedipine and amlodipine (1 nM) had no effect. BD (0.1-10 nM)
      enhanced the effects of 1,25(OH)2D3 on osteoblastic cells, the decreased cell
      growth and increased ALPase activity. These findings suggest that BD regulates
      the growth and differentiation of osteoblasts and stimulates the function of
      these cells as well as 1,25(OH)2D3.

PMID- 9576985
TI  - Bone mineral density in the chronic patellofemoral pain syndrome.
AB  - Bone mineral density (BMD) and clinical status of 40 patients with a chronic,
      unilateral patellofemoral pain syndrome (PFPS) were determinated. The mean
      duration of the disease at the time of the follow-up was 7.6 +/- 1.8 (SD) years.
      The BMD was measured at the spine (L2-L4), and the femoral neck, trochanter area
      of the femur, distal femur, patella, proximal tibia, and calcaneus of both lower
      extremities using a dual-energy X-ray absorptiometric (DXA) scanner. The mean BMD
      of the affected limb (compared with the unaffected side) was significantly lower
      in the distal femur (-3.3%; P = 0.002), patella (-2.5%; P = 0.016), and proximal
      tibia (-1.9%; P = 0.008). The femoral neck, trochanter area of the femur, and
      calcaneus showed no significant side-to-side differences, and the spinal BMDs of
      men and women with the PFPS were comparable with the manufacturer's age-adjusted
      reference values for Western European men and women. The relative BMDs of the
      affected knee showed strongest correlation with the muscle strength of the same
      knee: the better the muscle strength compared with the healthy knee, the higher
      the relative BMD (r = 0.56-0.58 with P < 0.001 in each anatomic site of the
      knee). In the stepwise regression analysis, low body weight or low body mass
      index, high level of physical activity, the patient's good subjective overall
      assessment of his/her affected knee, and short duration of the symptoms were also
      independent predictors of the high relative BMD in the affected knee so that
      along with the muscle strength these variables could account for 51% of the
      variation seen in the relative BMD of the femur, 61% in the patella, and 54% in
      the proximal tibia. In conclusion, chronic patellofemoral pain syndrome results
      in a significantly decreased BMD in the knee region of the affected limb. The
      spine, proximal femur, and calcaneus are not affected. Recovery of normal muscle
      strength and knee function seems to be of great importance for good BMD.

PMID- 9576998
TI  - Limited access atrial septal defect closure and the evolution of minimally
      invasive surgery.
AB  - While minimizing the "invasiveness" in general surgery has been equated with
      minimizing "access", what constitutes minimally invasive intra-cardiac surgery
      remains controversial. Many surgeons doubt the benefits of minimizing access when
      the need for cardiopulmonary bypass cannot be waived. Recognizing that median
      sternotomy itself does entail significant morbidity, we investigated the value of
      alternative approaches to median sternotomy using atrial septal defect closure as
      our investigative model. We believe that some, but not all minimal access
      approaches are associated with reduced postoperative morbidity and enhanced
      recovery. Our current strategy is to use a mini-sternotomy approach in adult
      patients, whereas conventional median sternotomy remains our standard approach in
      the pediatric population. Considerable clinical experiences coupled with
      documented clinical benefits are fundamental before a certain approach is adopted
      in routine practice.

PMID- 9576987
TI  - Soy protein isolate diet does not prevent increased cortical bone turnover in
      ovariectomized macaques.
AB  - Forty-one ovariectomized, cynomolgus monkeys were divided into 4 groups and fed a
      casein and lactalbumin based diet with or without 17beta-estradiol, or a soy
      protein based diet with or without 17beta-estradiol for 7 months.
      Histomorphometry was done on cortical bone from the mid-shaft femur. 17beta
      estradiol suppressed ovariectomy-induced increases in bone formation rates,
      regardless of dietary protein source. Soy protein alone did not prevent increased
      bone turnover and on the endosteal surface, it actually increased bone turnover
      when compared to casein/lactalbumin fed monkeys.

PMID- 9576999
TI  - Hemofiltration removes bradykinin generated in the priming blood in
      cardiopulmonary bypass during circulation.
AB  - After induction of hemofiltration for the hemic prime of a cardiopulmonary
      bypass, the initial drop in blood pressure disappears, and postoperative edema
      rarely occurs. We have suspected that bradykinin, a strong vasodilator generated
      through the activation of factor XII, prekallikrein, and high molecular weight
      kininogen was removed by ultrafiltration. We examined the changes in the
      activities of plasma-factor XII, prekallikrein, high molecular weight kininogen
      and in the levels of bradykinin in the priming blood using red cell concentrates
      before and after hemofiltration, and evaluated the effectiveness of
      hemofiltration. Ten circuits were used, and ten sets of blood samples were
      collected from red cell concentrates, the priming blood before hemofiltration,
      after hemofiltration, and the filtrate. During circulation in the circuit, factor
      XII, prekallikrein and high molecular weight kininogen were completely consumed
      and a large amount of bradykinin was generated, but it was filtered well by
      ultrafiltration. Factor XII, prekallikrein and high molecular weight kininogen
      could be activated through the dilution of red cell concentrates during the
      priming and contact with the circuits. Because bradykinin is the most potent
      vasodilator, increasing microvascular permeability and relating to several other
      inflammatory mediators, the removal of bradykinin generated from factor XII,
      prekallikrein and high molecular weight kininogen is very significant in the
      prevention of non-specific inflammatory reactions during and after open-heart
      surgery.

PMID- 9577000
TI  - Transmyocardial laser revascularization in the treatment of end-stage coronary
      artery disease.
AB  - Transmyocardial laser revascularization has been used in 171 patients suffering
      from severe angina pectoris unresponsive to medical therapy at Deutsches
      Herzzentrum Berlin within the period from 7/1994 to 12/1997. In all patients
      conventional bypass surgery or PTCA, did not seem to offer the possibility of
      success. Postoperatively, the majority of the patients experienced a significant
      decrease in angina and better physical endurance. A statistically significant
      increase in myocardial perfusion or left ventricular contractility has not been
      detected. Perioperative mortality after TMR decreased from 8% among the first 40
      patients to 2.5% among the 40 patients operated on most recently, with an overall
      mortality of 7%. The relief of angina symptoms and the improved quality of life
      after TMR seems to justify the use of the method in patients who presented with
      urgent indications for CABG surgery, although their coronary vessel status did
      not seem to promise success for this procedure. However, considering its
      experimental foundation and long-term effects, it seems that a conclusive
      assessment of TMR is not yet possible.

PMID- 9577001
TI  - Assessment of thoracic aortic atheroma by echocardiography: a new classification
      and estimation of risk of dislodging atheroma during three surgical techniques.
AB  - A new classification is described to improve precision of thoracic atheroma
      reporting. In 68 patients, the thoracic aorta was screened with epiaortic and
      transesophageal echocardiography. The thoracic aorta is divided into 6 zones
      corresponding to sites of aortic manipulation. Zones 1-3, proximal, mid and
      distal ascending aorta, Zones 4-5, proximal and distal arch and Zone 6, proximal
      descending aorta. Each zone is further sub-divided into anterior, left lateral,
      posterior and right lateral quadrants. There is a marked increase in moderate and
      severe atheroma between Zones 1-3 and Zone 4-6 (p<0. 001). There is a difference
      in atheroma by quadrant with the anterior the most frequent. (p<0.001) Once the
      grade and location of atheroma was classified, a comparison of the estimation of
      risk of dislodging atheroma during three surgical methods for care, was
      performed. Of 50 quadrants of atheroma, the composite arterial pedicle Y graft
      CABG would manipulate 5, Aortocoronary CABG with single aorta cross clamp, 16,
      and Aortocoronary CABG with aortic partial occlusion clamp, 21. This
      classification of 6 zones and 4 quadrants within each zone will increase the
      precision of atheroma reporting and allow better comparison of stroke reduction
      interventions.

PMID- 9577002
TI  - Surgical results of composite graft replacement of the aortic root aneurysm.
AB  - From 1986 to 1996, 20 patients underwent aortic root replacement. All of the
      patients had annulo aortic ectasia (AAE); Six had DeBakey type I aortic
      dissection, three were acute dissections associated with Marfan's syndrome; three
      had previously undergone the Koster-Collins operation. During 11 years, the
      original Bentall procedure (1986-91), the Cabrol procedure (1991-), and the
      modified Bentall procedure (Carrel patch or Piehler technique) were performed.
      There was only 1 hospital mortality (5.0%). Four patients died during the follow
      up period (mediastinitis, myocardial infarction, cerebral bleeding, and rupture
      of the arch aneurysm). Only 2 patients required reoperation (repair of a
      pseudoaneurysm of the right coronary artery and paravalvular leakage of the
      aortic valve replacement). The satisfactory outcomes were the result of the full
      thickness anastomoses performed during coronary artery reconstruction.

PMID- 9577004
TI  - Prosthetic valve thrombosis after abdominal surgical procedures: a case report.
AB  - A 63-year-old woman with a prosthetic mitral valve who developed valve thrombosis
      after abdominal surgical procedures is reported. She had undergone mitral valve
      replacement with a Sorin-Bicarbon valve 3 years previously, and was referred for
      an operation due to rectal cancer with anal bleeding. On admission, the patient
      was on oral anticoagulant therapy with warfarin, and the intensity of
      anticoagulation was around 40% of Thrombotest. Doppler echocardiography showed
      that the prosthetic mitral valve function was normal. Low anterior resection of
      the rectum was uneventful. Management of the perioperative anticoagulation was
      peformed with heparin, however, the postoperative anticoagulation using
      intravenous infusion of heparin was imperfectly achieved. Consequently,
      thrombosis of the prosthetic mitral valve occurred 8 days after the operation.
      Replacement of the thrombosed prosthetic valve was performed with successful
      results. The imperfect postoperative anticoagulation with heparin may have been
      the cause of the valve thrombosis. The management of perioperative
      anticoagulation during noncardiac operations is discussed.

PMID- 9577003
TI  - Clinical experiences of surgical repair for mitral regurgitation secondary to
      papillary muscle rupture complicating acute myocardial infarction.
AB  - Mitral regurgitation secondary to ischemic heart disease carries a significant
      mortality even after emergency open heart surgery. From 1993 to 1997, four
      patients were operated on for ischemic mitral regurgitation secondary to
      papillary muscle rupture. These patients were between 58 and 69 years of age and
      all were in class III or IV of the New York Heart Association Classification. The
      responsible infarction area was located in the lateral wall in 2 patients, and
      inferior in others. The interval between the onset of acute myocardial infarction
      and the appearance of mitral regurgitation was from 1 to 10 days. Three patients
      had partial rupture (defined as only one or several heads of papillary muscle
      ruptured), and one had total papillary muscle rupture. Primary mitral plasty was
      performed in 3 patients, including 1 patient who had undergone patch closure of
      ventricular septal perforation at the onset of acute myocardial infarction.
      Mitral plasty combined with coronary artery bypass grafting was performed in 1
      patient. Only one case, who had total papillary muscle rupture, required
      reoperation for recurrence of mitral regurgitation. We suggest that even in the
      case of ischemic mitral regurgitation, when a papillary muscle rupture is
      partial, mitral repair is performed because of its potential for improving
      therapeutic results.

PMID- 9577005
TI  - Emergency coronary artery bypass grafting after left coronary artery rupture: a
      case report.
AB  - Coronary artery rupture has been known as one of the complications of coronary
      balloon angioplasty. In this report, we describe a case of coronary artery
      rupture, who underwent emergency surgery for hemostasis and coronary
      revascularization. A 67-year-old-male with frequent angina attacks was admitted
      to our institution for possible coronary angioplasty. Coronary angiogram showed
      diffuse disease of the mid left anterior descending artery (LAD), with two 90%
      stenosis. Conventional balloon angioplasty was performed, however, coronary
      artery rupture occurred while the stent was expanded with a 3.5 mm balloon
      catheter. Though pericardial drainage improved his hemodynamic state, subsequent
      coronary angiogram revealed leakage of contrast medium. Emergency surgery was
      determined at this point for hemostasis and revascularization of the LAD. The
      revascularization was completed with the left internal thoracic artery (LITA) to
      the LAD. On the contrary, since the epicardial hemorrhage around the proximal LAD
      did not spread any further after systemic heparinization, the epicardial surface
      was covered with a piece of oxidazed cellulose and fibrin glue. After the
      surgery, the hemodynamic state improved gradually. Postoperative coronary
      angiogram revealed an aneurysm of the LAD, as well as excellent LITA-LAD patency.

PMID- 9577006
TI  - Sutureless ringed graft replacement of descending thoracic aorta with extensive
      calcification.
AB  - A 79-year-old hypertensive woman, with fusiform shaped atherosclerotic aneurysm
      in the descending thoracic aorta whose medial layer was maintained by an
      extensive solid calcium plate (porcelain aorta), was successfully treated using a
      sutureless intraluminal ringed graft. Spools of the ring were fixed by
      circumferential ligatures at both proximal and distal sites of anastomosis and a
      dilated segment of the aorta was replaced with the tube graft.

PMID- 9577007
TI  - A ruptured syphilitic descending thoracic aortic aneurysm. The characteristic
      findings on computed tomography for the etiological diagnosis of aneurysm.
AB  - We report the case of a 72-year-old man with a ruptured syphilitic descending
      thoracic aneurysm who underwent an emergency operation and successful graft
      replacement. Preoperative physical examination showed a pulsative mass on the
      left back. Preoperative computed tomography showed bone destruction in the TH6 to
      TH10 thoracic vertebrae and ribs and penetration (or rupture) of the aneurysm
      into the subcutaneous tissue. During the period of preoperative evaluations, free
      wall rupture of the aneurysm occurred and emergency operation for graft
      replacement was performed. The microscopical examination of the aneurysmal wall
      revealed the syphilitic changes. In literature, the vertebral destruction by
      atherosclerotic aneurysm is usually located at the TH12 to L3 of vertebral
      bodies. From the findings of this patient and a study of existing literature, we
      concluded that the finding of vertebral bone beyond TH12 to L3 region on CT
      examination of the aneurysm could be a etiological characteristic finding for
      syphilitic aortic aneurysm.

PMID- 9577008
TI  - Coronary artery surgery results 1996.
AB  - This survey on ischemic heart disease surgery began in 1974 and has continued to
      report the current status of surgical treatment in Japan. Coronary artery bypass
      grafting (CABG) has increased markedly and surgical results have become
      increasingly favorable. This report describes CABG and surgery for postinfarction
      complications in 1996, including the first investigation on CABG without
      cardiopulmonary bypass (off-pump CABG) and minimally invasive direct coronary
      artery bypass grafting (MIDCAB).

PMID- 9577009
TI  - Symptomatic treatment of neurolathyrism with tolperisone HCL (Mydocalm): a
      randomized double blind and placebo controlled drug trial.
AB  - The efficacy and safety of oral Tolperisone HCL was evaluated in double blind,
      placebo-controlled, randomized trial in 72 patients with neurolathyrism in stages
      I, II, and III of the disease at Kolla Duba Health Centre of Dembia District of
      North Gondar between January and April 1995. Taken orally daily for 12 weeks,
      tolperisone HCL (Mydocalm) in a dose of 150 milligrams (mgs) twice daily
      significantly improved subjective complaints such as muscle cramps, heaviness of
      the legs, startle attacks, flexor spasms and repeated falls. An overall
      subjective improvement was observed in 75% of the patients on tolperisone HCL and
      39% of the placebo group (P = 0.002). When objectively assessed spastic muscle
      tone in the abductors, stiffness of Achilles and spontaneous ankle clonus were
      significantly reduced in tolperisone HCL group (P values = 0.001, 0.04, and
      0.0001, respectively). Walking ability and speed of walking was also
      significantly improved. The drug is most effective in relieving symptoms of stage
      I and stage II disease. Some adverse effects like muscle pain, generalized body
      weakness and dizziness were recorded in patients taking the drug but all were
      minor and self limited, none requiring discontinuation of treatment. It is
      concluded that tolperisone is a well tolerated and efficacious drug for
      symptomatic treatment of neurolathyrism.

PMID- 9577010
TI  - Bacterial isolates from indigenous weaning foods in rural Ethiopian setting,
      Jimma Zone, south west Ethiopia.
AB  - A community based bacteriological study of weaning foods was conducted from
      November 1994 to August 1995 in six peasant associations, Jimma Zone. The
      households in the study community were found to be in poor sanitary conditions
      with cattle and pets living in the same room with humans, and the community gets
      water from unprotected sources. The predominant weaning foods in the study
      community were cereals. These and other foods given to weaning age children were
      found to be grossly contaminated, aerobic mesophilic bacterial counts being 10(5)
      cfu/ml of sample. The most frequent bacterial isolates were Enterobacter sp, Gram
      positive cocci including Staphylococcus aureus, Klebsiella sp., Citrobacter sp.,
      and Escherichia coli in that order. Various factors such as unsafe water,
      unhygienic handling of food, storage of food at ambient temperature for a long
      time, poor domestic and personal hygiene may have contributed for the gross
      contamination of weaning foods in the study community. This calls for educating
      the community on the relationship between contamination of weaning foods and
      diarrhoeal diseases, and promoting measures such as reheating of weaning foods
      which have been kept at ambient temperature for a long time before serving
      infants and children.

PMID- 9577012
TI  - Injection practice in north western Ethiopia.
AB  - A community based cross-sectional descriptive study was conducted in December
      1994 in Bahir Dar District, north western Ethiopia, to describe injection
      practices. Systematically selected 1380 households both from the urban and rural
      settings were included in the study. A two-week overall prevalence of injection
      therapy was found to be 13%. The rates were comparable in the rural and urban
      settings, as 12 and 14%, respectively. Diarrhoea and fever were the major
      symptoms for which injection was received. The informal health care providers
      were consulted more by the rural population than the urban. Disposable syringe
      and needle use was more common among the urban injection receivers. Age was the
      only factor observed to be significantly associated with the injection
      medication. A statistically significant (P < 0.05) higher injection treatment
      rate was observed among children under five. Improvement of the supplies of
      injection equipments and regular on-the-job training and supervision are
      recommended to improve the safety of injections.

PMID- 9577011
TI  - A four-year cohort study of HIV seropositive Ethiopian infants and children:
      clinical course and disease patterns.
AB  - Sixty-two HIV positive infants who were admitted to the Missionaries of Charity
      Orphanage in Addis Ababa were followed From July 25, 1991 to July 30, 1995 for a
      total period of 4 years. Regular clinical examination and treatment by a
      paediatrician was being offered to these infants in addition to monitoring of
      their HIV serostatus every three months until the age of 18 months and every year
      after that. Among those aged above 18 months, 14 children were HIV sero-positive
      and alive and 4 children were HIV sero-positive but died. Thirty-three children
      had sero-reverted to negative. The mother-to-child transmission was crudely
      estimated at 29% to 47%. Among the clinical signs, generalized lymphadenopathy,
      hepatomegaly, splenomegaly, wasting, stunting and delayed motor development were
      found more commonly in the definitely HIV positive children. Upper respiratory
      tract infections, acute diarrhoea, pneumonia, pyogenic skin infections, sepsis
      and candidal infections were the commonest causes of illness. Comparison of the
      HIV positive with the HIV negative cases indicates that the risk is higher for
      the indefinitely HIV positive group for episodes of acute diarrhoea, pneumonia,
      sepsis and candidal infections.

PMID- 9577014
TI  - Khat induced psychosis and its medico-legal implication: a case report.
AB  - It has been established that khat plant leaves (Catha edulis forsk) contain an
      active psychostimulant substance known as Cathinone that is similar in structure
      and pharmacological activity to amphetamine. There have been no previously
      reported cases of khat induced psychosis in Ethiopia despite heavy consumption of
      khat in most parts of the country. We report here a case of brief and episodic
      psychosis attributed to heavy khat chewing. We maintain that khat leaf is a
      substance of abuse and that Khat chewing has the potential to complicate
      psychiatric conditions and forensic events.

PMID- 9577013
TI  - Increased incidence of resistance to antimicrobials by urinary pathogens isolated
      at Tikur Anbessa Hospital.
AB  - A retrospective analysis of 2209 urine samples submitted for culture to the
      Microbiology Laboratory of the Tikur Anbessa Hospital (TAH), Addis Ababa, between
      January 1992 and December 1994 was made. Significant bacteriuria (colony count >
      10(5) colony forming units/ml urine) was detected in 672 (30%). Pure culture was
      obtained in 510 (23%) of all samples and polymicrobial growth was detected in the
      remaining 162 (7%). Gram-negative bacteria comprised 95% of all isolates. The
      commonest organisms being Escherichia coli (39%) and Klebsiella species (26%).
      Among the gram-positives, Staphylococcus aureus (57%) was the most common
      pathogen isolated. Most of the organisms were resistant to multiple drugs.
      Ampicillin, carbenicillin, chloramphenicol, tetracycline and trimethoprim
      sulphamethoxazole were effective in less than 30% of all cases. There was also a
      significant resistance to cephalothin, gentamicin and kanamycin. Only nalidixic
      acid and nitrofurantoin were effective for most of the organisms. Compared to
      previous studies, there is an indication of reduced effectiveness of the commonly
      prescribed antibiotics. The rational use of drugs should be practiced in order to
      prevent the emergence of multi-drug resistant microorganisms.

PMID- 9577015
TI  - Ruptured abdominal aortic aneurysm: a case report.
AB  - A 45 year old male patient presented with shock and abdominal mass to emergency
      medical Out Patient Department of the Police Force General Hospital in March
      1996. This patient was diagnosed to have ruptured abdominal aortic aneurysm and
      died shortly after admission. There have been, to our knowledge, no published
      data from Ethiopia regarding rupture of aortic aneurysm. We therefore present the
      first case. The clinical presentation, course and literature review will be
      presented.

PMID- 9577017
TI  - [Specific areas in pediatrics: the need for their recognition. A solution or a
      problem?].

PMID- 9577016
TI  - [Exploration of the nutritional status and body composition].

PMID- 9577018
TI  - [Head injuries in children: can clinical features identify patients with high or
      low risk for intracranial injury?].
AB  - OBJECTIVE: The objective of this study was to assess the clinical features that
      might reliably identify the presence of an intracranial injury. PATIENTS AND
      METHODS: A prospective study of 1,128 children with head injury over a one year
      period was carried out. Information regarding each patient was documented,
      including demographic data, physical examination findings, neurologic status,
      diagnostic studies and the patient's outcome. RESULTS: Of the 1.128 patients,
      traumatic intracranial abnormalities identified on CT of the head was found in 11
      (1%). Four patients of this group (36%) required surgery. Two children
      subsequently died. Loss of consciousness, amnesia. Glasgow Coma Scale less than
      15 and focal neurological deficits were significantly more common in the group
      with intacranial injury. The negative predictive values were high for all
      features. CONCLUSIONS: Patients with symptoms of head injury should undergo head
      CT because a small number will require surgery. After a minor head trauma,
      children who are neurologically normal and without symptoms may be discharged
      from the emergency department and sent home after careful physical examination
      alone.

PMID- 9577019
TI  - [Quadrivalent vaccine against diphtheria, tetanus, B. pertussis and hepatitis B:
      experience in Spain].
AB  - OBJECTIVE: The objective of this study was to perform a pooled analysis of the
      immunogenicity and reactivity results obtained in 2 trials carried out in Spain
      with a combined DTP-HB vaccine. PATIENTS AND METHODS: Vaccine was administered
      according to one of two existing vaccination schedules: 2-4-6 and 3-5-7 months of
      age. Blood samples for antibody determination were obtained 3-6 weeks after the
      third dose. Anti-diphtheria, anti-tetanus and anti- B. pertussis antibodies were
      measured by ELISA and anti-HB by radioimmunoassay. Local and general signs and
      symptoms were recorded by the parents on diary cards for a 4-day follow-up period
      after each vaccination. RESULTS: A total of 231 infants received three doses of
      DTP-HB vaccine. All of these doses were accompanied by the corresponding diary
      card (693 data points for the evaluation of reactogenicity). Two-hundred and
      nineteen subjects ere included in the analysis of immunogenicity. After the full
      vaccination course, all subjects had sero-protective titers against diphtheria,
      tetanus and hepatitis B and were sero-positive of B. pertussis. Geometric mean
      titers of anti-HB antibodies was 1986 mIU/ml. Pain at the injection site (64%)
      and unusual crying (71.5%) were the most frequently reported local and general
      symptoms, respectively. Fever (rectal temperature > or = 38 degrees C) was
      reported after 46% of the doses, but was considered as severe (> 39.5 degrees C)
      only in 5 cases. CONCLUSIONS: These results show that this combined DTP-HB
      vaccine induced a strong immune response to all vaccine components. The safety
      profile of this DTP-HB is similar to that of classical DTP vaccines.

PMID- 9577020
TI  - [Poland's syndrome. A report of 38 cases].
AB  - OBJECTIVE: The purpose of this study was to analyze the different hand anomalies
      observed in Poland's syndrome. PATIENTS AND METHODS: Thirty-eight clinical
      histories were revised. There were 28 boys and 10 girls. In 18 cases the right
      side was affected and in 20 cases the left side. Special attention was placed on
      the analysis of the anatomical hand findings, in both the clinical and
      radiographic studies. The patients were classified into 5 types: Type 1, without
      syndactyly; type 2 syndactyly and hypoplastic or aplastic middle phalanx; type 3
      or "shovel hand" with complete syndactyly also affecting the thumb; type 4
      longitudinal deficiency of some digits or radius and type 5 transversal absence.
      RESULTS: Four cases presented associated chest wall anomalies. We have observed
      four cases of type 1, 25 cases of type 2 (65.7%), 5 cases of type 3, 3 cases of
      type 4 and one case of type 5. The middle phalanx was hypoplastic in 15 cases,
      aplastic in another 15 cases and combined hypo and aplastic in 4 cases. In 18
      hands we observed two fissure plates in metacarpals. CONCLUSIONS: 1) We did not
      observe any side predominance.) Two fissure plates in the first metacarpus is
      frequently observed (78.2%). 3) We propose a classification according to the
      anatomical hand anomalies.

PMID- 9577021
TI  - [Perinatal care in multiple pregnancies].

PMID- 9577022
TI  - [Perinatal care in multiple pregnancies: an emergency situation or a disaster?].

PMID- 9577023
TI  - [Outcome at 3 years of age in a low birth weight cohort].
AB  - OBJECTIVE: The objective of this study was to establish the outcome at 3 years of
      age for very low birth weight newborns admitted to the Hospital 12 de Octubre
      from January 1991 to December 1993. PATIENTS AND METHODS: A follow-up study was
      performed. The pediatric assessment included a neurological, psychological,
      visual and audiological evaluation. At the end of the follow-up, children were
      blindly assessed to determine the rate of neurosensory disability. The severity
      of the neurosensory disability was graded as severe, moderate or mild by a
      functional classification. The rates of cerebral palsy, blindness and deafness
      were reported. RESULTS: Two hundred fifty-three infants between 500 and 1,499 g
      were admitted to the Hospital 12 de Octubre of which 182 survived. Of these, 137
      (75% of the survivors) were assessed at 3 years of age. The children who dropped
      out during the follow-up period had similar characteristics to those with a
      complete follow-up program except that the drop-out child was more likely to
      belong to a disadvantaged family. The rate of neurosensory disability was 28.5%
      (39/137), 16% were mild, 5% moderate and 7% severe. The rate of cerebral palsy
      was 13% (18/137), blindness 1.4% and deafness 0.7%. CONCLUSIONS: Children from
      more disadvantaged families are less likely to continue in follow-up programs and
      this supposes a bias in the follow-up program. At 3 years, neurosensory
      disability was diagnosed in 1 out of every 4 children and cerebral palsy in 1 out
      of 8 children.

PMID- 9577024
TI  - [Epidemiological aspects of children of women with bicornuate uterus].
AB  - BACKGROUND: Most published papers on women with a bicornuate uterus analyze their
      fertility problems, as well as certain pregnancy complications. We have not found
      any epidemiological study on the infants of mothers with this uterine
      malformation. Only in some papers a reference is made about the relationship of
      maternal bicornuate uterus with congenital deformations and disruptions in their
      infants. PATIENTS AND METHODS: Using data from the Spanish Collaborative Study of
      Congenital Malformations (ECEMC), which has a case-control methodology, some
      characteristics in a series of 26,945 malformed infants, such as birth weight,
      sex, gestational age, umbilical cord length, placental weight and maternal age,
      were analyzed by separating infants of mothers with normal uterus and those of
      mothers with a bicornuate uterus. RESULTS: Results showed that women with a
      bicornuate uterus have more daughters than sons and an increased risk for
      intrauterine growth retardation and prematurity with respect to infants of
      mothers with a normal uterus. On the other hand, the risk of having an infant
      with congenital defects is higher for women with a bicornuate uterus than for
      those with a normal uterus. CONCLUSIONS: Pregnancies of women with a bicornuate
      uterus have to be considered at risk since they have more risk for complications
      and for having an infant with congenital defects, premature birth and with
      intrauterine growth retardation.

PMID- 9577025
TI  - [The effects of acute fetal distress on neonatal behavior measured by the
      Brazelton scale].
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of fetal
      distress associated with metabolic acidosis (pH < 7.15 and BE < -8 in blood
      samples from umbilical artery) in neonatal behavior. PATIENTS AND METHODS:
      Infants were evaluated with the Brazelton Neonatal Behavioral Assessment Scale
      (NBAS) on the third day of life (60-84 hours) in the Clinic Hospital of
      Barcelona, Spain. Fifteen anoxic neonates (experimental group) were compared to a
      sample of eight-seven newborns (control group) with the same characteristics, but
      with normal pH and BE levels (pH > 7.25 and BE > -5). RESULTS: Statistically
      significant differences were found between the two groups. The control group
      performed much better than the experimental group in almost all of the NBAS
      clusters: habituation, orientation, autonomic, regulation of states and motor
      functioning. There were no differences between the groups in the cluster range of
      states. The anoxic newborns of this study showed more irritation, stress,
      hypersensibility and difficulties to modulate states than the neonates without
      this problem. CONCLUSIONS: The NBAS is a useful evaluation technique as a
      complement to the physical examination because it gives a detailed description of
      the newborn behavior and competence. Habituation (p = 0.002), orientation (p =
      0.000) and autonomic (p = 0.000) are the clusters who discriminate best between
      the groups.

PMID- 9577026
TI  - [Amplification of the clinical spectrum of the Robinow syndrome].

PMID- 9577027
TI  - [The birth of octuplets: a situation of multiple hospital emergency].

PMID- 9577028
TI  - [Anhidrotic ectodermal dysplasia. Two cases in twins].

PMID- 9577029
TI  - [Acute pain, analgesia and sedation in children (II): pharmacokinetics and
      pharmacodynamics in non-opioid analgesics].

PMID- 9577030
TI  - [Pena- Shokeir syndrome].

PMID- 9577031
TI  - [Evaluation of the infrared tympanic thermometer].

PMID- 9577032
TI  - [The sequence of fetal akinesia/hypokinesia, Pena-Shokeir syndrome, multiple
      congenital arthrogryposis and/or short umbilical cord: conceptual delimitation].

PMID- 9577033
TI  - [Carcinoma of the pancreas].
AB  - The extensive use of diagnostic tools has made possible easier diagnosis of
      pancreatic cancer. Nevertheless, sometimes histologic diagnosis is still lacking
      at the operation. However, it is not necessary for resection. Therapeutic
      management depends on surgeon's evaluation of anatomic situation, patient's age
      and general condition. Similarly, sometimes only surgical evaluation can show if
      cancer can be resected or not. Laparoscopy seems useful to detect small
      peritoneal metastases which can not be seen with other procedures. In the last
      years, reduction of morbidity and mortality is the main goal achieved. Excluding
      some selected surveys, long term survival is still disappointing.

PMID- 9577034
TI  - [Feasibility of exeresis. Controversial aspects in the surgery of carcinoma of
      the pancreas].
AB  - Pancreatic cancer has a dismal prognosis also after resection with a 5 years'
      survival of about 5% in operated patients. The main clinical issue in patients
      with a malignant tumour is to identify the ones that would benefit from a
      surgical treatment. Resectability of pancreatic cancer has not an absolute value
      and the possible advantages in terms of prognosis and quality of life should be
      balanced with surgical mortality and morbidity. For this reason the management of
      this disease involves a multidisciplinary approach and the surgeon should join
      with the other specialists in experienced oncology centers. En exhaustive
      evaluation of the following prognostic factors should be made pre and intra
      operatively to better define life expectancy with or without resection:
      Histotype: endocrine tumours and cystadenocarcinoma have, in general, a better
      prognosis, Staging: JPS classification has a better prognostic value if compared
      to the UICC. Completeness of the resection. Biological characteristics of the
      tumour. The main variables to be considered for the exeresis are: Size and local
      growth of the tumour (also considering the involvement of vessels,
      retroperitoneum and pancreatic capsule). Liver or peritoneal metastases: for this
      laparoscopy has a key role for staging. Histologic confirmation: differential
      diagnosis with chronic pancreatitis is sometimes difficult and every attempt
      should be made to have a pre-operative histology. Vascular invasion is one of the
      main contraindications to surgery and an exhaustive evaluation of vascular
      involvement should be considered mandatory. Lymph nodal involvement, in general,
      represents a negative prognostic factor even if Japanese authors claim that a
      radical resection can be performed in case of positive nodes in the
      peripancreatic area, if a complete lymphadenectomy is carried out.

PMID- 9577035
TI  - [Reconstruction technique after pancreaticoduodenectomy].
AB  - The many techniques proposed for the reconstruction of the digestive path after
      pancreaticoduodenectomy show the continuous research of the most anatomical and
      safest way to achieve the best results. Most of the technical variations concern
      the treatment of the pancreatic stump and are directed to prevent the pancreatic
      fistula that is the most frequent cause of postoperative mortality and morbidity.
      None of the pancreatico-digestive reconstruction ways is absolutely better than
      the others and we think neither the total obstruction of the Wirsung duct is the
      solution of the problem of the pancreatic fistula. The accuracy and technical
      precision, the availability to modify the technique in relationship to different
      anatomy and functional conditions of the pancreatic stump are essential to
      improve the results. To achieve this goal is decisive the experience and patients
      volume of the surgeon and of the institutional team.

PMID- 9577036
TI  - [Pancreatico-jejunal anastomosis with invagination on isolated loop after
      cephalic pancreatoduodenectomy].
AB  - The most frequent and most dangerous complication of the duodenopancreatectomy is
      pancreatic fistula due to dehiscence of the pancreatic anastomosis. A technique
      that uses a separate Roux en Y loop for pancreatic anastomosis, to reduce the
      fatal risks of the pancreatic fistula, has been initially reported more than 50
      years ago. With the development of the pancreaticogastrostomy, it seems
      interesting to present a procedure using an isolated loop for the pancreas; this
      technique is derived from those previously published, allowing a good
      intussuception of the pancreas in the intestinal loop. This method has been
      performed in 35 duodenopancreatectomy (malignant pancreatic disease: 32 patients,
      benign pancreatic disease: 3 patients). The mean age of the patients was 64 years
      (range 34-74). There were four operative deaths unrelated to the
      pancreaticojejunal anastomosis and two pancreatic fistulas with spontaneous
      healing. The pancreatico-jejunostomy using a separate Roux en Y loop represented
      in this short experience a safe procedure to prevent pancreatic fistula.

PMID- 9577037
TI  - [Treatment of the pancreatic stump after cephalic pancreatoduodenectomy].
AB  - Pancreatico-jejunal anastomosis still represents the main source of postoperative
      complications after pancreatoduodenectomy. In this study our experience on the
      occlusion of the residual pancreatic stump instead of pancreatico-jejunal
      anastomosis is reviewed. Between March 1981 and December 1995 we performed 223
      pancreatoduodenectomies using Neoprene injection into the Wirsung duct for
      pancreatic carcinoma of the head (123 cases), ampullary carcinoma (36 cases),
      distal bile duct cancer (23 cases), islet cells carcinoma (17 cases), chronic
      pancreatitis (11 cases), duodenal carcinoma (5 cases), miscellaneous diseases (8
      cases). Neoprene is a fluid, synthetic glue which polymerized and hardens when in
      contact with the pancreatic juice, inducing a fibrosis tissue which spares the
      endocrine component. We observed a 4.9% operative mortality (11 patients): 5
      abdominal sepsis, 1 DIC, 1 aortoiliac thrombosis, 1 pulmonary embolism, 1 stroke,
      1 hepatic failure, 1 cardiac failure. Overall morbidity was 44.8% (100 patients):
      in 25 cases (11.2%) a major complication requiring reintervention occurred. In 38
      patients (17%) pancreatic fistula was detected: median duration was 43 days, with
      a mean output of 5.3 ml/day; in all cases a spontaneous solution of the fistula
      was observed. In conclusion, intraductal injection of Neoprene after
      pancreatoduodenectomy is a safe procedure, it represents an useful alternative to
      pancreatico-jejunal anastomosis.

PMID- 9577038
TI  - [Total pancreatectomy. Which indications?].
AB  - This a review of the different topics held by literature for and against total
      pancreatectomy (TP) for adenocarcinoma of the pancreas. Technical and oncological
      aspects are discussed as are the metabolic effects of TP; metabolic data of our
      series of 6 TP are also referred. Postoperative mortality and morbidity decreased
      to less than 5% during the last decade both for TP and the Whipple procedure;
      long term survival is also similar for the two procedures. Even if the metabolic
      consequences of both exocrine and endocrine function deprivation are generally
      well compensated, they can still threaten the patient's life; furthermore their
      long term effects are only partially known. These are the reasons that force most
      authors to choose TP only in selected patients in which a multifocal neoplasia is
      demonstrated or whose pancreatic remnant is particularly soft and friable with
      high risk of pancreatojejunostomy complication. A pancreatic remnant in fact
      grants the hormonal milieu that makes easy the pharmacological control of any
      pancreatic function deficiency.

PMID- 9577039
TI  - [Intraoperative radiotherapy as adjuvant treatment for resection of carcinoma of
      the pancreas].
AB  - Local recurrence is the most frequent site of failure after resection for
      pancreatic cancer. We reported our experience in term of tolerance, local control
      and survival obtained by the association of resection and intraoperative
      radiation therapy (IORT). Between January 1985 and July 1996 152 resection for
      pancreatic cancer were performed at the authors' institution. For 77 patients,
      IORT was added to resection (group 1), whereas the other 75 patients underwent
      resection alone (group 2), because of either the unavailability of the linear
      accelerator or the patient's refusal. In group 1, radiation doses from 12.5 to 20
      Gy, with electron beam energies between 6 and 12 MeV, were delivered. Extension
      of the disease, percentage of radical resection and postoperative chemotherapy
      were similar in the two groups of patients. Operative mortality and overall early
      postoperative complications were respectively 1.3% and 31.2% in group 1 and 4%
      and 32% in group 2. The median survival was 17 months in group 1 and 15 months in
      group 2 and the median disease free survival was 12 months in group 1 and 8
      months in group 2. A local recurrence was detected in 31% of patients in group 1
      and in 49.3% of patients in group 2 (p < 0.1). The results suggest a better local
      control in patients with pancreatic cancer undergoing adjuvant IORT.

PMID- 9577041
TI  - [Neoplasms of the head and tail of the pancreas].
AB  - The majority of cancer of the pancreas-about 70%-arise in the head of the gland
      and only 20-30% in the body and tail. The latter usually have grown to a large
      size by the diagnosis is made, due to absence of symptoms. Jaundice is seldom
      present and pain is the main symptom. We reviewed recent literature, which
      present homogeneous data. Cancers of the body and tail are rarely resectable,
      with 30% morbidity and a much lower morbidity-0-10%-in specialized centres. If
      the lesion is localized and the patient in good physical condition, a laparotomy
      can be performed, with or without a preliminary laparoscopy to detect distant
      metastases. Distal pancreatectomy and splenectomy is the treatment of choice. In
      our experience, only tumors different from ductal adenocarcinoma have a good
      prognosis. Pain can be managed by surgical or chemical splanchnicectomy and, in
      selected cases, thoracoscopically.

PMID- 9577040
TI  - [Palliative treatment of pancreatic adenocarcinoma].
AB  - Carcinoma of the pancreas is the fourth leading cause of cancer related death in
      Western Countries. The 5-year survival for resectable tumors is 15-25%, while
      patients with unresectable neoplasms survive a median of 7 months. Only 30% of
      carcinomas of the head of pancreas and 10% of the body and tail are resectable
      for cure. Therefore, palliation of symptoms, namely obstructive jaundice,
      duodenal obstruction and pain, involve 80-90% of cases. Jaundice is frequent in
      tumors of the head. Palliative biliary decompression can be achieved by non
      surgical methods-endoscopically placed endoprostheses or percutaneous biliary
      drainage- or surgically. The former are indicated in patients with metastatic
      disease, high operative risk and short life expectancy. Surgical palliation which
      includes choledocho-duodenostomy, cholecystoduodenostomy, cholecystojejunostomy,
      hepato or choledocho-jejunostomy offers the advantage of providing a simple
      procedure that can treat or prevent all of the major symptoms: jaundice, duodenal
      obstruction and pain. Mechanical obstruction of the duodenum occurs in about 30%
      of cases in association with jaundice at the time of presentation and in 13-21%
      of patients previously subjected to biliary bypass after 8 months. Actual
      obstruction can be relieved by gastro-jejunostomy. Significant controversy
      remains concerning the role of prophylactic gastro-jejunostomy in patients
      requiring biliary diversion without signs of duodenal obstruction. Pain, which
      sooner or later affects the majority of patients, can be relieved by
      splanchnicectomy, either surgically or percutaneously.

PMID- 9577042
TI  - [Combined surgical treatment of pulmonary neoplasms with single brain
      metastasis].
AB  - The combined surgical treatment of primitive lung cancer with single brain
      metastasis is a frequently debated but still controversial problem. Up to day
      several therapeutic approaches are generally integrated (surgery, radiotherapy,
      chemotherapy) according to the clinical patterns and the technical possibilities.
      In general, the combined surgical operation (thoracotomy + craniotomy) when it is
      possible to be done, followed or proceeded by chemo-radiotherapy, has allowed to
      achieve a prolonged survival in these patients, maintaining an acceptable quality
      of life. The authors analyze 10 cases treated by thoracotomy and craniotomy at
      the Chair of Thoracic Surgery of University of L'Aquila. Although consisting of a
      small number of cases, this experience allows to detect the particular problems
      concerning these patients. The indications to the combined surgical treatment are
      considered, evaluating the surgical operation which is to be performed as first
      on the basis of lung cancer staging and of the location and size of the brain
      metastases. Finally the patients survival and their quality of life are
      considered.

PMID- 9577043
TI  - [Lithiasic, congenital, choledochal dilatation: problems of diagnosis and
      therapy].
AB  - We report a case of a 30-year old female with congenital lithiasic choledochal
      dilatation which was not diagnosed at the ultrasonographic examination.
      Congenital biliary dilatation abnormalities are rare and may clinically present
      with episodic biliary colics or more rarely with recurrent pancreatis.
      Ultrasound, CT-scanning and ERCP usually make these anatomic alterations evident
      but in some cases there may be some doubt despite the vast range of radiological
      techniques available (PTC, Tc99m-Isida scinti-scan). The best results from a
      diagnostic point of view are obtained from the ERCP that may in fact visualize an
      anomalous pancreatico-biliary junction, rule out carcinoma, accurately define the
      cyst dimensions or show the intrahepatic ductal radicals. Furthermore, the
      extraction of intracystic stones or the treatment of choledochocele through a
      papillostomy may be performed. However the ERCP may cause traumatic pancreatitis,
      above all in youngster as was verified in our patient. During surgical
      exploration, the definitive diagnosis can be achieved via intraoperative
      cholangiography. We emphasize that in patients with congenital choledochal
      dilatation, the dilated choledochus should be excised even in young children to
      avoid the risk of malignancy which may occur also following cyso-duodeno- or
      cystojejunostomy treatment. In our patient an hepatiocojejunostomy on a Roux-en-Y
      limb was performed. This single case has been oresented along with a review of
      the literature to recall such anomalies in differential diagnosis of biliary
      colics and to stress that the choice treatment is surgical resection.

PMID- 9577044
TI  - [Laparoscopic cholecystectomy during pregnancy].
AB  - BACKGROUND: We evaluated the advantages and risks of laparoscopic cholecystectomy
      during pregnancy in symptomatic patients. MATERIAL AND METHODS: Three gravid
      women at an estimated 14 to 26 weeks gestational age underwent laparoscopic
      cholecystectomy for symptomatic cholelithiasis or biliary pancreatitis. One
      patient was obese. The operation was successfully completed under tocolytic
      medication. DISCUSSION: Although rare, gallbladder disease is the second most
      common abdominal condition during pregnancy requiring operation, being second
      only to appendicitis. Medical management is the most common approach to
      treatment, and the surgical intervention is reserved for patients who fail to
      respond to conservative methods or who have choledocholithiasis, biliary
      obstruction or pancreatitis. The laparoscopic approach is controversial, and some
      authors still agree that pregnancy is a contra indication to laparoscopic
      cholecystectomy. We report our experience with three laparoscopic
      cholecystectomies performed without complication during pregnancy. On the basis
      of our experience and a review of the literature, we believe that the
      laparoscopic cholecystectomy, undertaken preferentially during the second
      trimester, is a valid alternative to classic management in terms of risks for the
      foetus and comfort for the mother.

PMID- 9577045
TI  - [Treatment of chronic pancreatitis today: considerations on 133 observed cases].
AB  - Aim of the work is to define the present role of surgery in the treatment of
      chronic pancreatitis and the criteria of choice of procedures. The authors
      examined retrospectively 133 patients. They analyze the clinical, laboratory and
      instrumental features on which has been formulated the surgical indications.
      Patients treated surgically were those who have intractable pain, jaundice,
      intestinal obstructions and bleeding. The choice of the procedure is based on the
      seat and type of the anatomo-pathological lesions and on the features of
      Wirsung's duct. 54 of the 133 patients observed have been treated surgically or
      with interventional radiology. The authors carried out 19 resections, 30 drainage
      procedures, 1 pancreatic biopsy, 2 percutaneous drainage, 1 perendoscopic
      papillotomy. Neither mortality nor morbidity were observed after radiological and
      endoscopic procedures, while after surgery we observed 3.9% of mortality and 9.4
      of total morbidity and 5.6% of specific morbidity, represented by a pancreatic
      leakage. The long term results were well in the patients who didn't take on
      alcohol. In conclusion the authors underline that the progresses of the medical
      treatment and the radiological and endoscopic procedures imply the decrease of
      number of patients undergoing surgical intervention. They remind that surgery
      maintain his importance and, when carried out with correct indications, permits
      to obtain an effective and lasting result of the symptomatology presented by the
      patient.

PMID- 9577047
TI  - Primary hyperparathyroidism sustained by a giant adenoma of the parathyroid
      gland.
AB  - A case of primary hyperparathyroidism sustained by an unusually large parathyroid
      adenoma is presented. The tumor affected a 45-year-old woman with a 15-year
      history of nephrolithiasis and presented as a palpable neck mass. On the basis of
      clinical findings and ultrasound examination, it was initially misdiagnosed as a
      thyroid nodule. CT scan and transesophageal endosonography gave a correct
      definition of the tumor, which was located behind the left thyroid lobe and
      expanded posterior to the pharynx and the esophagus in the prevertebral space. At
      surgery a parathyroid tumor measuring 8 x 7 x 3 cm and weighing 90 g was
      successfully removed. No signs of malignancy were observed by both morphological
      and cell kinetic analyses.

PMID- 9577046
TI  - [Ambulatory treatment of hemorrhoidal pathology with elastic bands according to a
      modified Barron technique].
AB  - The authors report their experience in the treatment of hemorrhoids by rubber
      band ligation according to Barron's modified technique which foresees that the
      ligation is performed thanks to the suction of the hemorrhoidal node through the
      shaft of the band applicator connected with an aspirator. Eighty-four patients
      underwent consecutively this treatment over a 18-month period; all were performed
      with a minimum follow-up of 6 months. Forty male patients (mean age 46.6 years)
      showed symptoms lasting since 9 years. Forty-four female patients (mean age 42.6
      years) showed such pathology since 8.9 years. 70.2% of the patients were
      classified as III stage of disease, 19% II stage and 10.7% I stage. Thirty-four
      patients had anal pain, 49 bleeding, 5 anemia, 21 thrombosis of the hemorrhoidal
      plexus, 54 prolapse of the ano-rectal mucosa. These symptoms and signs were
      present in most of the patients contemporaneously. Three patients had previously
      received rubber band ligations, 4 hemorrhoidectomy, 1 sclerotherapy and 1 rubber
      band ligation and sclerotherapy. In the whole we performed 285 sessions and 304
      rubber band ligations. Each treatment consisted of 3.4 sessions and 3.6 rubber
      band ligations. Recovery was achieved with only one session in 9 patients; 66.7%
      of them showed 1st degree disease. Multiple sessions were necessary in patients
      with advanced disease degree; 100% at stage II and 94.9% at stage III. Sixty-five
      patients did not refer immediate and long-term significant complications. The
      remaining patients complained during the first hours about heavy feeling and/or
      tenesmus and two, 2 weeks after the end of treatment, showed bleeding episodes,
      which cleared up spontaneously. In 5 cases it was necessary, during follow-up, to
      carry out a completion rubber band ligation and in 3 we performed trimming
      surgery at the out-patients' department by resection of the exceeding skin and
      anal mucosa. The technique enables to achieve results just as valid as those of
      traditional methods in the treatment of hemorrhoidal pathology with the advantage
      that it can be performed in an out-patient's department, it does not need local
      anesthesia, it enables the patient to immediately return to his normal working
      activity and, restricted to the observation period (6- and 12-month follow-up) it
      allows a satisfactory control of the disease.

PMID- 9577048
TI  - [Human fibrin glue in the treatment of residual parenchymal surface after total
      pericystectomy for hepatic echinococcus].
AB  - The aim of this study was to evaluate the presumed efficacy of fibrin sealant in
      limiting bleeding and biliary leakage from liver residual surface after total
      pericystectomy for hydatid disease. Forty-five patients (group A) who underwent
      total pericystectomy in our Institution from 1986 to 1995 and liver residual
      surface treated with conventional techniques and fibrin sealant for control of
      haemorrhage and bile leakage were selected. A control group (B) was carefully
      selected, matching the main characteristics of patients in group A: it consisted
      of 44 patients, who underwent total pericystectomy from 1981 to 1993 and in which
      fibrin sealant was not used. Postoperative hospital stay, morbidity, mortality,
      abdominal drainage discharge, perioperative variations of hemoglobin and
      hematocrit readings and the need for postoperative blood transfusion were
      evaluated in the two groups. A statistical analysis was performed. We found no
      statistical significance for the considered parameters in the two groups.
      Markedly no significative difference was found in morbidity, abdominal drainage
      discharge and need for postoperative blood transfusion. Our results do not allow
      a definite assessment of the actual role of fibrin sealant in rising efficacy on
      control of bleeding and biliary leakage from residual liver surface to total
      pericystectomy obtained with conventional haemostatic techniques. We believe that
      a previously planned controlled prospective trial could give the needed further
      elements to precisely evaluate the role of fibrin sealant in the surgical
      treatment of hydatid disease of the liver.

PMID- 9577049
TI  - The use of naltrexone to treat ambulatory patients with alcohol dependence.
AB  - The purpose of this study is to evaluate the efficacy of Naltrexone in decreasing
      craving symptoms among Puerto Rican male veterans with alcohol dependence.
      METHOD: This is a double blind placebo control study with a convenience sample of
      eleven patients divided in two groups (placebo and Naltrexone). Scales consisting
      of Zung Depression, Zung Anxiety, MMSE, OCD Screener, Craving, and Somatization
      were administered at baseline, and weekly for four weeks as follow up. RESULTS:
      There were no statistically significant differences between the two groups on any
      of the outcome variables at baseline or follow up measurements. A statistical
      trend was noted toward a decrease in somatization. A decrease in craving symptoms
      was observed in the experimental group. CONCLUSIONS: Even though our results did
      not show evidence of the efficacy of Naltrexone in decreasing craving symptoms, a
      small number of patients did benefit from the medication. The results could have
      been affected by the small sample size.

PMID- 9577050
TI  - [Pilot study of suicidal ideation among elderly Puerto Ricans in a mental health
      hospital].
AB  - This is one of the first descriptive-explorative studies done about suicidal
      thoughts in aging patients (age mean 60.7) within a mental health hospital in
      Puerto Rico. The purpose of this study was to identify common characteristics
      found in elderly patients that present suicidal thought and were hospitalized
      from January to June. The major finding indicates a great prevalence rate in men
      who were divorced, catholic, with a diagnosis on the axis I of the DSM IV and who
      had a previous history of such thoughts. In order to obtain a more comprehensive
      profile of the elderly patient with suicidal thoughts we suggest more research
      concerning this issue. Such investigations could be used in the prevention of
      elderly suicide.

PMID- 9577051
TI  - [Social support, activity, and health among the elderly].
AB  - The present study examined the relationship between social support, activity
      level and physical health among a sample of 96 Puerto Rican elderly persons. The
      Spanish version of the Inventory of Socially Supportive Behaviors (ISSB28) was
      used to assess social support. Two structured questionnaires were administered to
      obtain measures of activity level and physical health. A multiple correlation
      regression analysis was performed, and partial correlation coefficients were also
      obtained. A partial correlation of .48 (p < .001) was observed between the ISSB
      scores and the measure of physical health, indicating a direct relationship
      between poor health and social support. This finding is inconsistent with
      previous studies, which suggest that better health is associated with higher
      levels of social support. Moderate-low, negative correlations were found between
      activity level and 3 indicators of poor health. Thus, higher activity levels were
      associated with better physical health. For example, partial correlations of-.31
      (p = .003) and -.29 (p = .007), respectively, were found between the activity
      level and the number and length of hospital stays. The correlation between the
      amount of surgical interventions undergone by the patient during the previous
      year and the activity level was -.28 (p = .009). These findings demonstrate that
      higher levels of activity are associated with better physical health in elderly
      persons, as indicated by less frequent and shorter hospital stays, and lower
      frequency of surgical interventions. Several multiple regression analyses showed
      that social support and activity level, taken together, are statistically
      significant predictors of the number and length of hospital stays, and the number
      of surgical interventions undergone by the elderly patient. Together, these two
      factors explain from 11 to 18% of the variability in several indicators of
      physical health.

PMID- 9577052
TI  - Current role of chemotherapy protectors in cancer treatment.
AB  - The administration of full doses of chemotherapy according to an established
      schedule improves the response rate and duration of response in cancer patients.
      However, frequently there are delays in therapy due to dose-limiting side effects
      and chemotherapy could affect permanently normal tissues. This has led to the
      development of chemotherapy protectors and of rescue agents in the past years. We
      will discuss some of these new agents and their use in cancer treatment. Some of
      these agents include amifostine (Ethyol), dexrazoxane (Zinecard), mesna (Mesnex),
      leucovorin, G-CSF, GM CSF, recombinant erythropoietin and thrombopoietin.
      Oncologists must learn the adequate use of different strategies in reducing
      chemotherapy toxicity in order to improve both the quality and quantity of life
      of cancer patients.

PMID- 9577053
TI  - Prenatal diagnosis of right-sided diaphragmatic hernia: the use of color flow
      Doppler.

PMID- 9577054
TI  - Squamous cell carcinoma of the prostate: case report and review of literature.
AB  - Carcinoma of the prostate, that is adenocarcinoma, is one of the most common
      malignancies in the male with an estimated incidence for 1991 of 122,000 new
      cases. On the other hand, squamous cell carcinoma of the prostate, with a median
      incidence of .5%-1% of all prostatic malignancies, has a similar clinical
      presentation but differs in treatment response and prognosis. We herein present
      one case of this histological pattern and review the literature pertaining to it.

PMID- 9577055
TI  - Cecal volvulus after laparoscopic liver biopsy.
AB  - Laparoscopic surgery has become widely accepted due to its benefits of less post
      operative pain and shorter hospital stay. As with any other new technique, there
      are associated inherent complications. We present a case of cecal volvulus after
      laparoscopic liver biopsy. This is the first case reported in the literature of
      cecal volvulus secondary to laparoscopy.

PMID- 9577056
TI  - [Male pseudohermaphroditism caused by enzymatic deficiency of 17-alpha
      hydroxylase. 1st case reported in Puerto Rico].
AB  - A 36 year old white female came to our service after having been evaluated on
      repetitive occasions in the past for a workup of gigantism and acromegalic
      features. Since childhood she had developed tall stature, frontal bossing,
      prominence of zygomatic bones, separated teeth, large hands and size 14 shoes.
      Human growth hormone and somatomedin serum levels had been normal on all
      occasions tested. Her past history was significant for primary amenorrhea and a
      12 year history of hypertension. On physical examination BP was 140/100, height
      6' 2", weight 2571 bs. Her phenotype was truly acromegalic. There was absence of
      axillary and pubic hair with no breast development. External genitalia was of
      female appearance. Laboratory evaluation showed increased FSH of 88 mlU/ml,
      increase LH of 65.6 mlU/ml and decreased E2 of 12.6 pg/ml. Other findings were
      low serum cortisol of 0.2 mg/dl, high ACTH of 344 pg/ml, low 17-Ketosteroids,
      high pregnenolone levels of 595 mg/dl, low 17-hydroxypregnenolone less than 10
      ng/dl, very high aldosterone of 31 ng/dl and suppressed PRA of less than 0.1
      ng/ml. A pelvic sonogram showed a right ovoid structure which could represent a
      gonad and failed to identify the uterus and left gonad. A bone densitometry
      showed a decrease bone mineral density compatible with osteoporosis. Chromosome
      study showed a karyotype of 46-XY. A diagnosis was made of congenital adrenal
      hyperplasia secondary to 17-alpha-hydroxylase deficiency in a genotypic male. Our
      patient was referred to the department of gynecology for surgical removal of the
      gonads. It is amazing how a patient with severe adrenal insufficiency can
      withstand 36 years of her life undiagnosed without going into an adrenal crisis.
      Her tall stature and acromegalic features were the striking signs confusing all
      physicians and delaying the correct diagnosis and appropriate treatment. There
      has been reported worldwide, nearly 120 cases with documented severe 17-alpha
      hydroxylase deficiency. To our knowledge this is the first case identified in
      Puerto Rico of male pseudohermaphroditism secondary to 17-alpha-hydroxylase
      enzyme deficiency.

PMID- 9577057
TI  - What is your diagnosis?

PMID- 9577058
TI  - Brief report: successful extension of the transplant renal vein with a synthetic
      vascular graft.
AB  - Unexpected intraoperative vascular complications in the graft of the recipient
      during organ transplantation can be most vexing and require immediate attention
      and careful management so as not to impair the integrity and fate of the graft.
      We were confronted with a diabetic recipient with total fibrosis of the left
      iliac vein, patent inferior vena cava, totally and circumferentially calcified
      aorta and left iliac artery with the exception of a small area in the distal
      external iliac artery. The problem was solved by anastomosing the artery low onto
      the external iliac, and by interposing a venous polytetrafluoroethylene vascular
      graft between the renal vein and the inferior vena cava. The kidney function was
      excellent for 2 years but the patient succumbed to unrelated liver complications.
      A second patient with a renal vein PTFE graft has had normal graft function for
      10 years. Probably because of the high blood flow through the kidney, venous
      synthetic grafts can be successfully used to correct venous problems during
      kidney transplantation.

PMID- 9577059
TI  - [The responsibility of the surgeon for the actions of operating room personnel in
      the light of Toro Aponte vs ELA].

PMID- 9577060
TI  - Adult bone marrow transplantation in Puerto Rico: past, present, and future.

PMID- 9577061
TI  - Measles surveillance: guidelines for laboratory support. Working Group on Measles
      Elimination.

PMID- 9577063
TI  - [Anorectic and bulimic eating disorders--new developments. 2: Spectrum of
      evaluated therapy measures].
AB  - Therapeutic approaches to eating disorders--in particular the restrictive form of
      anorexia nervosa--should, in the first instance, be directed towards improving
      the patient's physical state of health. In addition, psychotherapeutic management
      of the interoceptive and emotional perception disturbances that are also usually
      present makes good sense (e.g. by cognitive behavioral therapy, video
      confrontation of the patient with her own appearance). On the other hand,
      disturbances in emotional expression also need to be addressed, and inadequate
      social skills improved. On an individual basis, the question must be investigated
      as to how far chronic stress, and/or major events in the patient's life are
      involved, or whether conflicts within the family or a partnership may be of
      significance for the initiation and maintenance of an eating disorder.

PMID- 9577062
TI  - [Anorectic and bulimic eating disorders--new developments. 1: Definitions,
      clinical manifestations and etiopathogenesis].
AB  - In western industrial countries, anorectic and bulimic eating disorders have
      appreciably increased in recent decades. For the most part, but not exclusively,
      the victims of such disorders are young women. The eating disorders may be
      understood as a failed attempt to resolve such problems as feelings of
      insecurity, anxiety and a lack of self-esteem. Anorexia nervosa continues to be a
      very serious illness with a high mortality rate. Numerous medical complications
      can be observed in anorexia nervosa and in bulimic eating disorders in normal
      weight (bulimia nervosa) and overweight (binge eating disorder) patients. The
      etiology is multifactorial. Bulimic eating disorders (bulimia nervosa) in
      particular, whether in normal-weight or overweight patients, have recently been
      investigated scientifically.

PMID- 9577064
TI  - [Eating disorders and sexual abuse. Significance of childhood stress--abuse is
      not a specific risk factor].

PMID- 9577065
TI  - [Severe osteomalacia in endemic sprue. An important differential diagnosis in
      osteoporosis].
AB  - A 67-year-old woman has a 20-year history of recurrent abdominal pain, diarrhea
      and diffuse bone pain. During the course of numerous hospitalisations the
      diagnoses "iron deficiency anemia", "iron absorption disorder", "osteoporosis"
      and "hyperparathyroidism" had been made. Despite treatment with vitamin D3,
      calcium, fluorides and iron, the patient's condition deteriorated to such a
      degree that she became in need of constant care. After 20 years of illness,
      nontropical sprue (celiac disease) with secondary intestinal osteopathy was
      identified. High-dose parenteral treatment with vitamin D3, oral calcium
      supplementation and a gluten-free diet resulted in an improvement of the
      patient's condition within three months, and the patient can now largely look
      after herself again.

PMID- 9577066
TI  - [Follicular cysts].

PMID- 9577067
TI  - [Association between medication with calcium antagonists and increased
      cardiovascular mortality is not established].

PMID- 9577068
TI  - [Choice of drug and indications are deciding factors].

PMID- 9577069
TI  - [HSV-1 is also involved].

PMID- 9577070
TI  - [Diverticulitis and appendicitis--often an atypical course in the elderly].

PMID- 9577071
TI  - [Diverticulosis and diverticulitis in the elderly].
AB  - Diverticulosis of the colon is a disease that mainly affects the elderly,
      presenting in 10 to 20% of this age group. The most common complication--painful
      diverticular disease, is usually treated conservatively with a high-fiber diet,
      intermittent use of antispasmodics and possibly regulation of the stools.
      Diagnostic differentiation is best performed using ultrasonography of the bowel
      wall, supplemented where necessary by computer tomography and colonoscopy
      (sigmoidoscopy) or, where this latter is not possible, barium enema using
      Gastrografin. Conservative treatment of diverticulitis with antibiotics, bowel
      rest, possibly including parenteral alimentation, is usually applied for three to
      ten days. In the absence of a response to this treatment, frequent recurrence,
      immunosuppression or complications (perforation, peritonitis, enterovesicular
      fistula), surgery is indicated.

PMID- 9577072
TI  - [Acute appendicitis in advanced age].
AB  - In the elderly, both the diagnosis and treatment of acute appendicitis require
      particular attention. The diagnosis is often made very late with 40% to 80% of
      the cases already having perforated. Reasons for the delayed hospitalisation
      include atypical course, reduction in sensitivity to pain in old age, and an
      inadequate ability to communicate. The prognosis of uncomplicated appendicitis is
      just as good in the old as in the young patient, but perforation and concomitant
      diseases worsen the situation appreciably. Early operation is therefore
      desirable. The preference of the author is for open, rather than laparoscopic,
      appendectomy.

PMID- 9577073
TI  - [Dietary fiber--stepchild in nutrition, which has much benefit. Patients with
      diverticulosis must get their intestines functioning].

PMID- 9577074
TI  - [Comorbidity in dementia. Are Alzheimer patients physically healthier?].

PMID- 9577075
TI  - [Contraception per computer. Hormone system persona--results of studies in
      Germany].

PMID- 9577076
TI  - [Spinocellular carcinoma].

PMID- 9577077
TI  - [From postal service to medical practice. The convoluted life course of the
      Hamburg pediatrician Dr. Klaus Gritz].

PMID- 9577078
TI  - [Liver resection in hepatocarcinoma and metastasis of colorectal carcinoma].

PMID- 9577079
TI  - [Surgical therapy of metabolic liver diseases (glycogenosis,
      hypercholesterolemia)].
AB  - Up-to-date, most patients with serious chronic hepatic disease are best treated
      by liver transplantation. It has been confirmed the striking benefit of liver
      transplantation also for patients with glycogen storage disease or homozygous
      familial hypercholesterolemia who were refractory to medical treatment.
      Nevertheless, the advantage of achieving palliation without transplantation,
      thereby avoiding the need for chronic immunosuppression, is obvious. With
      reference to the mentioned above diseases, end-to-side portacaval shunt was used.
      A favourable effect was noted on body growth and a number of metabolic
      abnormalities. Hepatic failure did not occur, although in a few patients blood
      ammonia concentrations and serum alkaline phosphatase levels increased relative
      to preoperative values. To avoid an incomplete palliation provided by portacaval
      shunt, appropriate case selection is a problem. The Authors report their personal
      experience with portacaval shunt for the treatment of glycogenosis and familial
      hypercholesterolemia.

PMID- 9577080
TI  - [Cholecysto-choledochal lithiasis: ideal laparoscopic cholecystectomy and
      choledochotomy versus sequential endoscopic-laparoscopic treatment].

PMID- 9577082
TI  - [Rare complications of biliary sepsis].
AB  - The surgical approach to the acute biliary pathologies also today is often
      controversial. The choice of the right time to operate an acute patient is based
      either on personal clinical experiences, either under the statement that waiting
      for the resolution of the acute process could be preferable in the aim of reduce
      the surgical risk. This is the almost general tendency. Recently, some
      interesting articles issued by Swedish and German schools conducted as controlled
      trials on a great base of cases, try to emphasize the advantages of an early
      surgical therapy, particularly in the elderly patients. In these ones, in fact,
      the concomitance of cardiovascular, metabolic and immunodepressive pathologies
      makes more serious the complications too. In this article, the Authors refer on
      three clinical cases, all of which were quite different, and in which it was
      possible to identify a former septic hepato-biliary pathology. All the patients,
      upon hospital admission showed an acute pattern. In two cases it was an hepatic
      abscess, accompanied in one case by a "satellite" pulmonary abscess on the right
      lung. These two were treated conservatively, although by a TC-guided drainage of
      the liver abscesses. The third case, a localized choleperitoneum (biloma
      saccatus), underwent an operation. The accurate investigation on the clinical
      records of Authors' Department since 1980 to 1995 and in particular on the three
      referred cases seems to confirm that the importance of some complications after
      acute biliary pathology and their great morbidity must stimulate the surgeons to
      investigate always on the real causes of all clinical patterns, even if uncommon.

PMID- 9577081
TI  - [Thymoma, aplastic anemia, hypogammaglobulinemia and malignant pulmonary
      neoplasm: a case report].
AB  - A 67 year old man presented with non-invasive thymoma, associated aplastic anemia
      and important hypogammaglobulinemia; the postoperative course has been
      characterized, three months later, by thrombocytopenia (kept under control with
      steroid therapy) and, two years later, by squamous lung cancer, not susceptible
      of surgical treatment. The patient died five years after operation because of
      progression of the lung cancer. Anemia improved only partially after operation;
      there where no effects on hypogammaglobulinemia. Thymoma has been reported in
      literature in 50% of patients with aplastic anemia, 7-13% of adult patients with
      hypogammaglobulinemia is affected by thymoma, in 21% of patients that presented
      with thymoma other tumors have been discovered through clinical history.

PMID- 9577083
TI  - [Hurthle cell neoplasms of the thyroid gland].
AB  - From 1986 to 1996 the Authors have surgically treated 34 patients affected with
      Hurthle cell neoplasm of the thyroid (23 benign and 11 malignant). Preoperative
      diagnosis was obtained mainly by fine needle aspiration biopsy. In thyroid
      surgery we routinely prepare laryngeal nerve and take great care to avoid
      devascularization fo the parathyroid glands. Operative procedures performed were
      hemithyroidectomy plus isthmectomy (18), subtotal thyroidectomy (2) and total
      thyroidectomy (14). No cervical lymph node dissection was requested, neither we
      observed post-operative morbidity. Mean follow-up was 116 months. During
      observation period we documented. No hematogenous metastasis was observed. All
      patients are now well and alive free of disease. This series stresses the
      favourable behavior of Hurthle cell neoplasm of the thyroid--even through a
      prolonged follow-up. A thorough review of the Literature on the topic is
      conducted. The Authors are in favour of total thyroidectomy as first choice
      procedure for lesions larger than 40 mm in order to reduce the need of completion
      thyroidectomy and the potential morbidity.

PMID- 9577084
TI  - [A case of paraneoplastic Conn's syndrome in a patient with pulmonary neoplasm].

PMID- 9577085
TI  - [Acute occlusion of the abdominal aorta].
AB  - The Authors report on two cases of acute aortic occlusion, related to cardiac
      embolism and thrombosis of aortic aneurysm. The singularity of the etiology adds
      interest to a pathology which is already, in itself, serious and complex and
      which requires the intervention of the surgeon, anesthesiologist-reanimator,
      cardiologist, and nephrologist. The diagnosis is mainly clinical. The use of
      Doppler and CT scan provide to achieve the diagnosis. Surgical treatment included
      transfemoral embolectomy, with a Fogarty catheter, in the patient with acute
      aortic occlusion related to cardiac embolism, and aortobifemoral bypass, in the
      other patient, affected by thrombosis of aortic aneurysm.

PMID- 9577086
TI  - [Current status of the use of the endoscopic cholangiography technique].
AB  - The endoscopic retrograde cholangiopancreatography as a diagnostic technique
      employed to obtain an accurate radiological study of the biliary path, and the
      biliary duct-pancreatic-duodenal junction. However, during the initial diagnostic
      studies, both echography and nuclear magnetic resonance have taken a priority.
      Currently, their importance is as a preliminary diagnostic method during
      endoscopic intervention.

PMID- 9577087
TI  - Adjuvant arteriovenous fistula in infrapopliteal bypasses.
AB  - The poor results obtained with the use of prosthesis in infrapopliteal arterial
      bypass grafting for critical limb ischaemia led to the introduction of several
      types of adjuvant arteriovenous fistula to improve the patency and limb salvage
      rates in patients who have no suitable autologous vein. The main aim of
      adjunctive arteriovenous fistula in infrageniculate prosthetic bypass is to
      accelerate the blood flow velocity through the prosthetic graft above the
      thrombotic threshold level. Since they are subject of great debate among vascular
      surgeons, the Authors have briefly reviewed the haemodynamic aspects and results
      reported with the use of such procedures.

PMID- 9577088
TI  - Mucosal immunology and the eye.

PMID- 9577089
TI  - Immunity in early life.

PMID- 9577090
TI  - Regulation of KIR expression in human T cells: a safety mechanism that may impair
      protective T-cell responses.
AB  - Killer-cell inhibitory Receptors (KIRs) are a new family of major
      histocompatibility complex (MHC) class I-specific receptors. KIRs allow natural
      killer cells to identify and lyse self cells that do not express sufficient
      amounts of MHC class I molecules. Here, Maria Cristina Mingari and colleagues
      view the expression of KIRs by cytolytic T lymphocytes and their regulation by
      certain cytokines as a double-edged sword.

PMID- 9577091
TI  - How the MHC selects Th1/Th2 immunity.
AB  - While the effects of cytokines on T helper 1 (Th1)/Th2 differentiation are well
      documented, it is less clear why a dichotomy of effector cytokine production
      would initiate from antigen-specific lymphocytes. Nevertheless, in defined
      experimental systems, the interaction between T-cell receptor (TCR), peptide and
      major histocompatibility complex (MHC) can determine Th1/Th2 dominance. Here,
      Joseph Murray discusses how TCR affinity and ligand density might interface with
      innate forces in the selection of CD4+ T-cell functions.

PMID- 9577092
TI  - Probing degeneracy in T-cell recognition using peptide combinatorial libraries.
AB  - Recent studies have demonstrated flexibility of the T-cell receptor (TCR) with
      respect to recognition of peptide bound to self major histocompatibility complex
      (MHC). With the introduction of peptide combinatorial libraries, it has become
      possible to dissect the extent of degeneracy in T-cell recognition. On the basis
      of these novel findings, Bernhard Hemmer and colleagues propose a conceptual
      framework for lymphocyte selection and survival and the occurrence of
      autoimmunity.

PMID- 9577093
TI  - Inhibition of leukocyte adhesion: an alternative mechanism of action for anti
      inflammatory drugs.
AB  - It has been widely accepted that the mechanism of action of nonsteroidal anti
      inflammatory drugs (NSAIDs) is the inhibition of prostaglandin synthesis.
      However, a significant body of evidence suggests that NSAIDs have additional anti
      inflammatory mechanisms of action. Here, Federico Diaz-Gonzalez and Francisco
      Sanchez-Madrid discuss novel effects of NSAIDs on leukocyte adhesion pathways
      that may help in the development of new anti-inflammatory agents that selectively
      block cell adhesion molecules.

PMID- 9577094
TI  - Immune responses to dietary antigens: oral tolerance.
AB  - The concept of immunologically mediated tolerance to food antigens through
      exposure to mucosal antigen has been the subject of continuous scientific debate.
      After a decline in interest in the mid-1980s, oral tolerance has again attracted
      the attention of immunologists. Here, Stephan Strobel and Allan Mowat discuss how
      this central immunological principle has potential new therapeutic applications
      for the treatment of autoimmune, inflammatory and possibly food-allergic
      diseases.

PMID- 9577095
TI  - The molecular basis of leukocytosis.
AB  - The function of any known gene is often found by DNA or protein homology
      scanning. Conversely, it is equally rewarding to search for the genetic basis
      behind a known function. Here, Ghislain Opdenakker and colleagues examine the
      known and possible novel genes and molecular events underlying the phenomenon of
      leukocytosis, one of the most common clinical manifestations of inflammatory
      problems.

PMID- 9577096
TI  - Nitrergic mechanism of DC-mediated T-cell elimination.

PMID- 9577097
TI  - Beta-endorphin in immune cells.

PMID- 9577098
TI  - Two classes of MHC class II interactions with the TCR.

PMID- 9577099
TI  - The immunobiology of zinc and the kidney.

PMID- 9577100
TI  - Feedback.

PMID- 9577102
TI  - Computer-aided automated landmarking of cephalograms.
AB  - The computer-aided method presented is able to interpret and measure radiological
      structures automatically and reproducibly on a large number of randomly selected
      lateral head films of different film quality. For example the hard and soft
      tissue expression of the profile is used to discuss method, application and
      disadvantages. The performance of the system depends on image quality. The
      algorithm cannot be influenced by opacifications due to metal structure. In 90%
      of all cases the contours are identified correctly. Even if the image quality is
      poor, the recognition rate is about 84%. The selected cephalometric landmarks are
      placed in the right way in 85% of all cases. The constraint mathematical
      conditions and the high reproducibility improve the quality process of the
      cephalometric analysis. Recognition rates of 84% to 90% justify even nowadays the
      routine use of semi-automatic systems in PC-based analysis. With advancing
      digital radiography and improved computer performance, image interpreting systems
      will certainly become established.

PMID- 9577101
TI  - Long-term development in the mandible and incisor crowding with and without an
      orthodontic stabilising appliance.
AB  - In children with dentoalveolar Class II malocclusion with proclined upper
      incisors treated with extraction of the maxillary first premolars and appliance
      in the upper jaw only has been reported to increase the lower arch crowding when
      compared with children with untreated normal occlusion. Stabilising orthodontic
      appliances might therefore be useful in the lower jaw. A comparison was made of
      Class II: 1 malocclusion with extraction in the upper arch in 35 individuals in
      whom a fixed orthodontic appliance was used in the upper arch only and 26
      individuals with fixed appliances in both jaws. The mean age at the start of
      treatment was 12.9 and 12.8 years, respectively. Treatment effects and post
      retention changes up to 4 to 5 years out of retention at the age of 20 to 22
      years were evaluated from lateral head films and plaster casts. During treatment
      the orthodontic appliance in the lower arch relieved crowding. The available
      lower anterior space increased from -0.6 to +0.2 mm, compared, to a decrease from
      -0.4 to -1.3 mm in the group without mandibular appliances. After 4 to 5 years
      out of retention the lower arch available space had decreased in both groups, to 
      1.4 mm in the group where orthodontic appliances had been used in both jaws and
      to -2.5 mm in the group without an orthodontic appliance in the lower jaw. This
      difference was significant. But the subjective ranking of the amount of crowding
      in the lower jaw models showed no significant difference between the 2 groups at
      the age of 20 to 22 years.

PMID- 9577103
TI  - In vitro testing of a measuring system for in vivo recording of orthodontically
      applied forces and moments in the multiband technique. Part II.
AB  - The aim of this study was to measure in vivo the forces and moments acting
      therapeutically on the individual tooth in connection with the multiband
      technique. Securing and evaluating the planned in vivo measurements involves
      analysing the measuring accuracy of the system as a whole by means of
      corresponding in vitro investigations. Errors in determining the therapeutically
      effective force system may result from the electrical measurement of the
      mechanical quantities by the sensor system and from the fixing of the archwire in
      therapeutic position. The precision of this fixing is influenced by displacements
      induced by elasticities and mechanical tensions in the measuring system.
      Calibration test series have shown the sensor system to have a margin of error of
      less than 2%. The displacements influencing precision fixing of the archwire were
      determined by means of a laser position measuring system. For a maximum
      orthodontic force of 1.5 N, they are 0.06 mm in the least favourable case. The
      resulting measuring accuracy was determined analytically or graphically,
      depending on the key parameters. Successful in vivo studies of the
      therapeutically applied force systems are to be expected on the basis of these
      results.

PMID- 9577104
TI  - A three-dimensional photographic method for documentation and measurement of
      dental conditions.
AB  - A 3-D photographic technique was developed for the registration of bite
      conditions. This technique may replace plaster models for archiving purposes. To
      achieve this, photographic equipment and computer programs should be user
      friendly, not too expensive, and allow measurements that satisfy scientific
      demands. This purpose was fulfilled by combining the following elements: a
      photographic unit with standardized conditions for 3-D photography and a
      reference object with known coordinates where bite impressions or models are
      placed during photography. To reconstruct 3-D coordinates from photographs these
      are placed on a digitizer connected to a computer programmed for reconstructing 3
      D coordinates from the digitized 2-D data. The accuracy of the 3-D reconstruction
      of coordinates, x, y, z, was tested by means of 3-D photographs of a test object
      with reference points having a precision of +/- 0.5 micron. The mean error for
      distances of 5 mm and 15 mm varied between -0.17 mm and +0.15 mm. Measurements of
      45 degrees and 90 degrees angles had an accuracy that varied from -0.5 degree to
      +0.9 degree and from -1.2 degrees to +1.5 degrees respectively. An angle between
      lines and a plane of 54.7 degrees displayed a mean error of +/- 1.6 degrees. The
      test of the accuracy of the 3-D photographic technique for calculating distances
      and angles demonstrated that it fulfills demands for scientific applications on
      clinical material.

PMID- 9577106
TI  - Psychology subjects for post-graduate orthodontic training. A pilot program
      according to the ERASMUS guidelines.

PMID- 9577107
TI  - Frankfurt University Orthodontic Postgraduate Program as a pilot project of Hesse
      State Dental Council.

PMID- 9577105
TI  - Radiographic evaluation of apical root resorption with 2 different types of
      edgewise appliances. Results of a randomized clinical trial.
AB  - The purpose of this paper was to compare radiographically the prevalence and
      degree of apical root resorption after treatment with a fully programmed edgewise
      appliance (FPA) and a partly programmed edgewise appliance (PPA) in a randomized
      multipractice clinical trial. Two groups of patients with Class II malocclusions
      were treated orthodontically. The type of treatment was randomly assigned by a
      computer program. During fixed appliance therapy, one group was treated according
      to the precepts of the straight wire concept (FPA; n = 32) while the other was
      treated with conventional full edgewise mechanics (PPA; n = 29). Treatment times
      were recorded. Radiographs of the maxillary incisors were made before and after
      active treatment with fixed appliances using the bisecting angle technique. To
      correct for different projecting angles the pairs of radiographs were digitally
      reconstructed. The prevalence and degree of root resorption were assessed. The
      mean treatment time was 1.8 years and 1.6 years for treatment with FPA and PPA,
      respectively. The mean amount of loss of tooth length was 8.2% for the patients
      treated with FPA and 7.5% for the patients treated with PPA. No statistically
      significant differences could be assessed between both groups at the end of
      active treatment. The mean prevalence of apical root resorption was 75% for the
      patients treated with FPA and 55% for the patients treated with PPA. Statistical
      evaluation showed no significant differences. We concluded that the prevalence
      and degree of root resorption is independent of the appliances as used in this
      study.

PMID- 9577109
TI  - Spontaneous vertebral artery dissection resulting in Wallenberg's syndrome: a
      case report.

PMID- 9577108
TI  - Maternal mortality in Kentucky.
AB  - This paper reviews maternal mortality in Kentucky over the 30 year period of 1966
      through 1995. Data were reviewed from the minutes of the State Maternal Mortality
      Study Committee and the reports of the State Cabinet of Health Services, State
      Centers for Health Statistics. There has been a marked fall in the number of
      births during this 30 years and an even more dramatic reduction in maternal
      mortality. Identifiable causes for maternal death have changed over the years.
      Today, the three leading causes of maternal mortality in Kentucky mirror those of
      the nation, i.e., hemorrhage, pulmonary embolus, and toxemia.

PMID- 9577110
TI  - Warfarin vs enoxaparin for deep venous thrombosis prophylaxis after total hip &
      total knee arthroplasty: a cost comparison.
AB  - BACKGROUND: Total joint replacements are high-risk procedures for development of
      deep venous thrombosis (DVT) and pulmonary embolism (PE), therefore, routine
      pharmacological prophylaxis should be instituted in all cases. Cost-containment
      has become an important factor with the present changes in health care. This
      report presents an economic model for DVT prophylaxis after total hip and total
      knee arthroplasty (THA & TKA) that approximates closely to the current standards
      in orthopedic practice, and encourages the balance of clinical and economic
      considerations in patient care management. METHODS: A simplified cost
      effectiveness (cost-minimization) analysis, from the consumer's perspective,
      between Warfarin and Enoxaparin for DVT prophylaxis after THA and TKA, for a
      total of 15 days, in both inpatient and outpatient settings was used. The costs
      of drugs, laboratory, and home care services were evaluated through surveying
      three different providers in each category and obtaining the mean value for each
      of the services supplied. All providers were located within the Louisville, KY,
      metropolitan area. Data collection took place in October 1996. RESULTS: The main
      outcome measure was the difference in cost between the two drugs when all factors
      associated with therapy were considered. The overall cost of DVT prophylaxis with
      Enoxaparin was somewhat less expensive ($925.38) when compared to Warfarin
      ($971.77). CONCLUSIONS: Within the limitations of this study Enoxaparin was
      slightly more cost-effective than Warfarin for venous thromboembolism prophylaxis
      after total hip and knee arthroplasty.

PMID- 9577111
TI  - The problem with assumptions.

PMID- 9577112
TI  - A real doctor.

PMID- 9577113
TI  - [Levels of selected cytokines in aqueous humor of patients with cataract
      extraction].
AB  - AIM: The purpose of the investigation was to evaluate the presence of IL-1 beta,
      IL-2, IL-6, IL-8, TNF-alpha, IFN-gamma in aqueous humor of patients with
      cataract. MATERIALS AND METHOD: Aqueous humor was taken from 29 patients during
      extracapsular cataract extraction. The presence of cytokines was evaluated using
      immunoenzymatic methods. RESULTS: IL-2, IL-6, IL-8, TNF-alpha and IFN-gamma were
      found in all aqueous humor samples. There was no evidence for the presence of IL
      1 beta. CONCLUSION: Cytokines may play role in the inflammation process after
      extracapsular cataract extraction.

PMID- 9577115
TI  - [Evaluation of acquired color vision defects by means of the two equation method
      in primary open-angle glaucoma with normal pressure and in patients from the risk
      group].
AB  - PURPOSE: To evaluate acquired color vision defects in glaucoma patients and
      glaucoma suspects. MATERIAL AND METHODS: 52 subjects (102 eyes) divided into four
      groups (with primary open angle glaucoma, normal tension glaucoma, ocular
      hypertension and with glaucoma-like optic disc) were examined with the IF-2 All
      Color Anomaloscope. In all cases both the red-green equation of Rayleigh and the
      blue-green equation of Moreland were tested and three variables were determined:
      setting (matching) range (SR), calculated mid point (matching mid point) (CMP)
      and anomalous quotient (AQ) as compared to control group. RESULTS: No significant
      changes were found in the variables of the Rayleigh equation. However, in the
      blue-green equation SR was significantly enlarged in all tested groups and CMP
      was significantly shifted towards the short wavelength end of the match in first
      three groups. These results indicate a diminution of the color discriminating
      sensitivity in the short wavelength half of the visible spectrum and diminution
      of the blue cone sensitivity in glaucoma patients as well as in ocular
      hypertension (p < 0.001). In patients with glaucoma-like optic disc the setting
      range was enlarged in less degree (p < 0.01) without changes in the remaining
      variables (p > 0.05) what may be indicative of early stage of disease before the
      perimetric changes. CONCLUSION: Blue-green colour vision testing with the
      anomaloscope may serve as an additional test in the diagnostics of glaucoma.
      Glaucoma suspects with blue colour vision disturbances require the most careful
      investigation and if need be the recommendation of early treatment.

PMID- 9577114
TI  - [Comparative analysis of changes in the visual field in primary open-angle
      glaucoma and glaucoma with normal tension].
AB  - PURPOSE: To compare the pattern and the depth of visual field defects of POAG and
      NTG patients. MATERIALS AND METHODS: The visual fields in two groups of POAG and
      NTG patients, each counting 25 eyes, were analysed statistically. All eyes were
      tested at least twice, employing full threshold G2 test of Octopus 101
      (Interzeag) automatic perimeter. The tests with the highest reliability level
      were included. The analysis was performed using Peridata (Interzeag) statistical
      package. Mean values of mean defect (MD), corrected loss variance (CLV) and
      compound index (CI) for each group were acquired. Furthermore, main values of MD
      for upper and lower hemifield, quadrants and 10 degrees concentric rings, were
      obtained. The differences between the two groups were tested for the statistical
      significance. RESULTS: Values of all three above parameters (MD, CLV i CI) were
      significantly lower in the group of eyes with POAG as compared with those with
      NTG. In both groups mean MD was higher in the upper hemifield, but the
      upper/lower hemifield ratio was significantly higher in the POAG group (1.50) as
      compared with NTG group (1.05). In POAG group the highest mean MD was found in
      the upper-temporal quadrant whereas in NTG group the lower-nasal quadrant was the
      most affected. In both groups the highest values of mean MD were found in the
      outer ring between 20 degrees and 30 degrees of visual field but the difference
      between the centre and periphery was considerably lower in NTG group.
      CONCLUSIONS: The results support the opinion that there exist differences between
      the patterns of visual field changes in POAG and NTG. The loss tends to be more
      diffuse in POAG, showing deeper defects in the periphery and stronger tendency to
      affect the upper hemifield.

PMID- 9577116
TI  - [Risk factors for age-related macular degeneration].
AB  - PURPOSE: To present the results of examinations of the risk factors for age
      related macular degeneration (AMD) carried out in the last 3 years. MATERIAL AND
      METHODS: Our clinical material comprised 119 patients, 69 women and 50 men, aged
      43-85, mean age 70 years. Using classification according to the worse eye, there
      were 20 patients with drusen, 27 with atrophic changes and 72 with exudative form
      and AMD. The following risk factors were evaluated: age, sex, body mass index,
      history of general medical conditions, cigarette smoking, sun exposure, family
      history of AMD and ocular conditions such as iris color, lens opacities,
      hyperopia, gerontoxon and changes in retinal vessels. RESULTS: The significant
      relationships were found between the development of AMD and the age of patients,
      as well as between the advanced forms of AMD and the history of cardiovascular
      diseases and sclerotic changes in retinal vessels, 87% of examined patients have
      light iris and 52% body mass index above 26. CONCLUSIONS: The studies confirmed
      the role of age in the development of AMD and indicated cardiovascular
      disturbances, increased body mass index and light iris as the possible risk
      factors for AMD that are most worth further studying. The special attention
      should be also paid to drusen as the risk factor of AMD.

PMID- 9577117
TI  - [Age related macular degeneration as a cause of blindness].
AB  - PURPOSE: To present our studies concerning the causes of blindness in age-related
      macular degeneration, including the relationship with risk factors for this
      disease. MATERIAL AND METHODS: A total number of 158 eyes with AMD in 99 patients
      were examined. Among them there were 21 cases with visual acuity 0.1 or less in
      the better eye. This group of patients underwent a detailed analysis in order to
      determine the factors responsible for visual impairment in comparison to the
      patients with better visual function. RESULTS AND CONCLUSIONS: Blindness is
      connected mostly with exudative AMD. There are no significant differences in
      prevalence of risk factors for AMD between the group of patients with visual loss
      and that of patients with visual acuity above 0.1. The majority of patients
      referred to the ophthalmologist too late and on account of that is should be
      necessary to perform prophylactic examinations of the people above sixty.

PMID- 9577119
TI  - [A case of invasive corneal and conjunctival cancer].
AB  - The paper presents a case of a 44 years old man, K.Z., with an invasive carcinoma
      of cornea and conjunctiva of his left eye. The patient was hospitalized for the
      first time eight years ago due to a viral keratitis of this eye, afterwards for
      three times due to changes within his cornea and conjunctiva in form of a
      cauliflower-like whitepink small tumour at the conjunctiva-cornea border line.
      During his last hospitalization the change covered two thirds of the cornea and
      it was going over onto the bulbar conjunctiva. The fourfold cytological and
      histopathological assays of the change did not show carcinomatous cells, but only
      cells of multi-layer, flat epithelium with features of excessive cornification.
      It is only the last histopathological assay of the cut-off small tumour that
      showed that it was carcinoma planoepitheliale keratodes invasivum. The consultant
      radiologists recommended removing the eye bulb since high radiation doses, which
      would be necessary, would destroy the eye bulb and yield postradiation reactions.
      The histopathological assays of the enucleated eye bulb confirmed the diagnosis
      and showed the superficial infiltration of the conjuctiva border. The patient was
      subjected to the X-ray treatment over the conjunctival sac region.

PMID- 9577118
TI  - [Evaluation of some vision components after implantation of bifocal and monocular
      intraocular lenses].
AB  - Short and long distance vision as well as vision in twilight conditions and
      dazzle sensitivity in 2 groups of 30 persons have been compared. In one group
      Corneal-Dual bifocal intraocular lenses and in the other group monocular lenses
      were implanted. In the former group 0.75 or nearer vision acuity was obtained
      without any additional correction, while in the latter group obtention of such
      vision required additional correction to +/- +2 4.0 D sph. Vision in twilight
      conditions and dazzle sensitivity were similar in both groups, though clearly
      lower than normal. The study also presents indications and contraindications for
      implantation of bifocal lenses.

PMID- 9577120
TI  - [A case of Cogan-Reese syndrome (iris nevus syndrome)].
AB  - A case of 37 years old woman with a classic form of Cogan-Reese iris naevus
      syndrome is presented. Closure angle glaucoma, being a part of syndrome, with
      glaucomatous disc damage was initially treated with drugs (betaxolol, trusopt)
      without effective IOP decrease. A surgery was performed (goniotrepanatio by
      Fronimopoulos modified by Palmberg, but without iridectomy), 5 fluorouracil
      subconjunctival injections were given to the patient postoperatively for 5 days.
      We received a good IOP control on the level of 12 mm Hg. The visual acuity was
      1.0 after surgical procedure. We wanted to present this case because of its
      rarity and a typical surgical procedure (without applying iridectomy).

PMID- 9577121
TI  - [Gout as a cause of uveitis].
AB  - The paper presents the case of a serious uveitis not yielding to a conventional
      therapy. After an insight differential diagnostics it was found that the gout
      made the disease etiology. After including a specific therapy an improvement in
      the local status was achieved.

PMID- 9577122
TI  - [Epidemiology and risk factors for age related macular degeneration].

PMID- 9577123
TI  - [Historical outline of glaucoma diagnosis and therapy].
AB  - The author presents history of development of views on glaucoma diagnostics and
      therapy. A special attention is paid to the role of Polish ophthalmologists.

PMID- 9577124
TI  - [Diagnostic possibilities of left ventricular systolic-diastolic volume curve
      computed in patients with vascular diseases by means of multigated radionuclide
      angiocardiography].
AB  - MATERIALS AND METHODS: In this study the multigated radionuclide angiography was
      performed in 54 patients with and without vascular diseases; the humeral arterial
      pressure was measured and the BMI was calculated in each patient by mean of the
      weight and height. The curve expressing the variations of the sisto diastolic
      volume of the left ventricle was generated from an analysis of the radioisotopic
      angiocardiography, and the curve, the BMI and the arterial pressure were used to
      calculate 14 different numeric values for each patient consisting of hemodynamic
      parameters of the left ventricular function. The diagnosis for each patient was
      then examined a posteriori and the patients were divided in 15 groups of which 1
      with non-cardiovascular pathologies and 14 with cardiovascular pathologies alone
      or in association. A statistical analysis was performed to ascertain whether the
      parameters could be used to classify patients into the diagnostic groups using
      the Fisher's discriminant analysis. RESULTS: The obtained classification agreed
      in the 63% of the cases. CONCLUSIONS: This paper proved the possibility offered
      by the curve expressing the changes in the sisto diastolic volume of the left
      ventricle to discriminate between the various cardiovascular pathologies.

PMID- 9577125
TI  - [Renal transplant rejection. Role of color Doppler sonography and comparative
      evaluation of fluorometric and bioptic results].
AB  - BACKGROUND: Aim of this work is to evaluate the morphological changes of the
      waveforms found in the parenchyma of the renal transplant rejection, establishing
      the prognostic significance. METHODS: 46 patients with symptomatic renal
      allograft underwent color Doppler ultrasound examination. The ultrasound
      characteristics were evaluated. The Resistive Index (RI), the morphological
      waveforms (divided into two groups: group A with regular waveforms, group B with
      irregular waveforms). Color Doppler pattern (R.I. and waveforms) were compared to
      histological and cytological specimens and to mean values of creatinine before
      and after therapy. RESULTS: In group A, the creatinine values varied between the
      start of rejection symptoms and after some days, giving a significant statistic
      result. Group B didn't show any important variations. The RI mean value was
      higher in group B. Significant results concerning correlation between Doppler
      parameters and histological specimens were not observed. CONCLUSIONS: The
      conclusion is drawn that in renal transplant rejection it is important to keep in
      mind also the variation of the waveforms to establish the clinical prognosis.

PMID- 9577126
TI  - [Natriuretic peptides and the heart. Critical review and application].
AB  - This paper deals with a literature survey on natriuretic peptides (NP) and their
      clinical use in prognostic stratification and therapy of arterial hypertension
      and cardiac failure. After a brief historical introduction, the phylogenesis of
      NP is analyzed and the reasons of their preservation in the evolution are
      emphasized. The biochemistry of the NP is then treated, and the structure,
      synthesis, mechanism of cellular action and systems of regulation are analyzed.
      Subsequently, the authors have analyzed the physiology of the NP as well as their
      hemodynamic and biohumoral effects and actions on the central nervous system. A
      literature review on the significance of NP in arterial hypertension, on their
      usefulness as indicators of damage and on their therapeutic practice is then
      made. In particular, the possible future applications in the prevention of
      atherosclerotic damage are analyzed. The significance of NP and of their
      metabolites in heart failure and the prognostic implication of these peptides
      particularly in ischemic heart failure are then discussed. The most important
      papers on this topic are described. Finally the studies on the use of NP in the
      therapy of heart failure are analyzed and a guide on research of this topic is
      defined.

PMID- 9577127
TI  - [Iatrogenic false aneurysm of the ulnar artery. A clinical case and review of the
      literature].
AB  - Nowadays false aneurysms have become an important part of the workload of a
      vascular surgeon as a result of the increasing number of iatrogenic arterial
      trauma occurring during diagnostic and therapeutic procedures requiring puncture
      or exposure of blood vessels. A case of a false aneurysm in the ulnar artery
      caused by a simple syringe needle during an intravenous cannulation is reported.
      The clinical symptoms and details of the diagnostic procedure based upon color
      Doppler and angiography are examined. The vascular operation consisted in
      proximal and distal arterial control, resection of the aneurysm and end-to-end
      anastomosis. After surgical treatment the patient experienced an excellent
      anatomic and functional recovery.

PMID- 9577128
TI  - [A new infusion method for a prostacyclin analogue].
AB  - BACKGROUND: Iloprost, a prostaglandin I2, is chemically stable and it has been
      successfully used by intravenous infusion in severe limb ischemia. Usually
      Iloprost is diluted in 0.9% sodium chloride solution and infused intravenously
      for six hours each day for 28 days in hospital. METHODS: In the present study
      after the first three days of infusion with a traditional pump in hospital, a
      home pump has been utilised for the infusion of Iloprost at home. This device
      allows the continue infusion of Iloprost at a flow rate of 2 ml/h for six days,
      then the pump is filled with a new solution. The home pump consists of a
      protective shell in polycarbonate (10 x 12 cm), 270 ml of volume, inside there is
      a balloon reservoir (3 membranes) which is filled with Iloprost. The structure of
      Iloprost does not change into the home pump as evidenced by HPLC studies and its
      continue infusion allows plasmatic high levels of its active isomers during the
      28 days of therapy. In 30 patients, 25 men and 5 women (mean age 61 years) with
      Fontaine stage IIB (6), III (5) and IV (19) POAD Iloprost has been infused with
      the home pump. The follow-up period was 1 to 16 months. RESULTS: The results have
      shown 4 major amputations and 1 death, in 9 patients complete pain relief and
      ulcer healing, and in 6 patients only improvement in relief of rest pain and
      ulcers. CONCLUSIONS: All the patients appreciated this system of infusion because
      they had a normal life; in addition it is less expensive because the patients
      stay in hospital only 3 days.

PMID- 9577129
TI  - [Treatment of breast cancer. Future perspectives].

PMID- 9577130
TI  - [Gastric cancer. Which resection?].
AB  - BACKGROUND: The choice of surgical technique in antral gastric cancer is still
      debated. Some authors support total gastrectomy in all cases. In recent years
      there is a trend to use total gastrectomy only if strictly necessary. Total
      gastrectomy allows a large lymph node excision, with better oncological results.
      The mortality rate and post-operative complications are quite similar today after
      gastric resection. Anyway, if exact histological diagnosis is possible and at
      least 6 cm unaffected tissue is preserved, oncological cure is possible by
      gastric resection. METHODS: Personal experience in 224 patients operated on from
      1975 to 1994 is reported. RESULTS AND CONCLUSIONS: 54.3% had antral gastric
      cancer, 16.5% body cancer and 8.7% fundus gastric cancer. Subtotal gastric
      resection should be the surgery of choice in antral gastric cancer. Early
      subtotal gastrectomy with R2, Advanced (III and IV-TNM) only resection with R2,
      and Advanced (II-TNM) total gastrectomy with R3.

PMID- 9577131
TI  - [Video laparoscopy in patients with pain in the right iliac region].
AB  - The authors report on their experience of 235 laparotomy operations and 125
      laparoscopic operations performed on patients with right lower abdominal pain.
      Concerning each of these different approaches, the authors analyzed and compared
      preoperative diagnosis, anatomo-pathological findings, intraoperative and early
      post operative morbidity and hospital stay. The ratio of negative open
      appendectomies was 24.1% (56 cases out of 233). The laparoscopic approach,
      performed on 88 cases of suspected appendicitis, allowed to document and to treat
      other pathologies, real causes of the lower right abdominal pain, in 42 cases
      (47.7%). The rate of conversion from laparoscopic appendectomy to open
      appendectomy was only 2.19% (2 cases out of 91). The morbidity rate of
      laparoscopic appendectomy was estimated at 6.5% (4.4% major complications, 2.2%
      minor complications). The morbidity rate of open appendectomy was estimated at
      8.9% (0.4% major complications, 8.5% minor complications). Though the median
      postoperative stay, after laparotomy approach, was slightly longer (2.6 days
      versus 2.4 days), the difference was not statistically significant. Based on
      these results, the authors conclude that the laparoscopic approach should be
      reserved for fertile female patients, especially when the diagnosis of
      appendicitis is uncertain.

PMID- 9577132
TI  - [Technique of repair of acquired inguinal hernia by anterior reinforcement of the
      Fruchaud floor with polypropylene mesh].
AB  - The main cause of acquired inguinal hernia is weakness of Fruchaud's deep
      muscolofascial floor, following metabolically-determined collagen disorders. A
      technique for the anterior reinforcement of this structure with polypropylene
      mesh is described here. Following intermuscular decollement, the mesh is placed
      in direct contact with the surface formed by the transversalis fascia and the
      transversus abdominis muscle and stretched as extensively as possible. Because
      the posterior aspect of the inguinal canal is the true barrier to abdominal
      pressure, the author believe that its direct reinforcement, without interposition
      of the internal oblique muscle, constitutes the most correct anatomo-surgical
      approach to hernia repair. This is the case for both indirect hernias, in which
      the internal ring is reconstructed at a deeper level, and for direct hernias, in
      which the "tent effect" of the prosthesis is prevented. Ninety-two primary
      inguinal hernias (56 indirect, 29 direct and 7 direct and indirect) in 87
      patients were repaired with this technique. Seventy-nine patients were followed
      up from 2 to 24 months. Early complications included: 7 ecchymosis, 3 seromas, 2
      subcutaneous infections, 3 testicular swellings. Incision and testicular pain for
      longer than 6 months occurred in 2 cases. No prosthetic infections or recurrences
      have been detected up to the present.

PMID- 9577133
TI  - [Surgical treatment of thyroid diseases in geriatric patients].
AB  - Thyroid diseases have a characteristic evolution in geriatric age, whether for
      the symptomatology frequently mingled with typical manifestations of again, or
      for glandular involution. Moreover, in the aged patient, the particular aspect of
      the epidemiology, physiopathology, clinic and therapy are to know and interpret.
      In most cases, the presence of a uni- or multi-nodular goiter does not cause
      compression problems or cancerization risk. In the presence of these problems and
      in multi-nodular goiter, we prefer total thyroidectomy because, at the present
      time, it is possible to put at zero the risks of this operation, neither we fear
      hypothyroidism which all the same also appears in less extensive operations.
      Between thyroid diseases, cancer has a typical biological behaviour and prognosis
      in geriatric patients. While most tumors have a better curability in geriatric
      age, these have a worse prognosis. So therapeutic indications very as a function
      of age. About this the authors present preliminary data of a prospective trial
      started in 1992.

PMID- 9577134
TI  - [Experience at an ambulatory surgical service for thyroid diseases].
AB  - Based of a personal series of 206 patients, the authors evaluate their personal
      experience of an outpatient surgery ward for thyroid pathologies. The paper
      reports the diagnostic and therapeutic approaches both in patients undergoing
      surgery and those who do not. Attention is focused on the importance of the
      multidisciplinary team and the quality of the results of a homogeneous follow-up.

PMID- 9577135
TI  - [Varicocele in young recruits].
AB  - The authors, after an examination of the literature on the subject, present the
      results of a retrospective study in which the incidence of varicocele among
      selected young soldiers population called up at SARVAM (Viterbo) from May 1993
      until October 1995 is evaluated.

PMID- 9577136
TI  - [Physiopathology of pneumoperitoneum].
AB  - INTRODUCTION: Laparoscopic surgery contributes to many clinical advantages, but
      pneumoperitoneum in human body has new physiopathological consequences. MATERIALS
      AND METHODS: The aim of this study was to review recent literature about the
      effects of pneumoperitoneum. Cardiovascular, pulmonary and liver functions were
      examinated after pneumoperitoneum. RESULTS: There is a correlation between the
      increase in intra-abdominal pressure and properties of gas chosen (CO2 vs
      helium). There is a correlation between serum level modifications of liver
      functionality in postoperative laparoscopic surgery. CONCLUSIONS: Laparoscopic
      surgery has contributed to many clinical advantages (postoperative pain
      reduction, swift resumption, etc.), but pneumoperitoneum modifies physiological
      function. The aim of our next work will be the assessment of postoperative liver
      function, without clinical symptoms.

PMID- 9577137
TI  - [Intestinal occlusion caused by Morgagni-Larrey diaphragmatic hernia].
AB  - Morgagni-Larrey's hernias, which are both infrequent and generally asymptomatic,
      are often diagnosed by chance during routine diagnostic tests performed for other
      pathologies. Usually congenital in adults, they are often small or only take the
      form of a pre-hernia lipoma. Intestinal occlusion is rarely described and
      frequently entails diagnostic difficulties before hydroaerial levels are
      demonstrated in the thoracic region. In these cases, surgery using an abdominal
      approach should be preferred in order to treat compressed abdominal viscera at
      the same time and to exclude the bilateral nature of the lesion. The authors
      present two cases of an adult man and woman who were referred to their attention
      for occlusive pathologies. Both were operated using a laparotomy approach. The
      reduction of abdominal viscera did not present any difficulties. The hernial sac
      was only removed in the first patient. Plastic surgery was completed by attaching
      the diaphragmatic flap to the costal and sternal wall using separate non
      reabsorbing suture stitches. No complications were reported.

PMID- 9577138
TI  - [Complicated Spigelian hernia. A case report].
AB  - Prompted by the observation of a case of lateral ventral Spigelian hernia
      complicated by strangulation and manifested by symptoms of small intestine
      occlusion, the authors describe the anatomo-surgical characteristics of the
      abdominal site of this pathology. They analyse the various diagnostic and
      subsequently surgical options available to the surgeon when dealing with this
      pathology. This is achieved with reference to data reported in the current
      international literature on the subject. Lastly, the authors provide a series of
      evocative images obtained during the diagnosis of the patient treated and of the
      results achieved following surgery and a 1-year follow-up after the operation.

PMID- 9577140
TI  - [Mucinous cystadenocarcinoma (malignant mucocele) of the cecal appendix].
AB  - Mucinous cystadenocarcinoma of the cecal appendix is a very rare malignant
      neoplasia. The majority of these tumours are discovered during surgery performed
      for other pathologies or as a chance finding in the histological analysis of
      surgically removed inflamed appendix. There is no characteristic symptomatology
      of this neoplasia which requires oncologically correct surgery, such as right
      hemicolectomy. The authors report a case study o peritoneal recidivation of a
      mucinous cystadenocarcinoma of the appendix.

PMID- 9577139
TI  - [Lithiasis of the vermiform appendix. Remarks on a clinical case].
AB  - The authors present a case of a 36 year old male, admitted with a 3 year history
      of cramping abdominal pain, fever, and transient finding of a right lower
      quadrant mass. The abdominal roentgenogram revealed a large opacity located on
      the right side of the fifth lumbar segment. The patient underwent laparotomy: an
      enlarged appendix was removed. The specimen had 4 calculi completely obstructing
      the lumen of the appendix. The diameter of calculi were 0.5 (in 3 instances) and
      3 cm. The case herein described is rather uncommon, due to: 1) the rarity of
      multiple appendiceal calculi; 2) the size of the larger stone; 3) the inconstant
      finding of right lower quadrant mass; 4) the non development of acute
      appendicitis. Differential diagnosis involved several diseases presenting with
      palpable mass of the lower quadrant of the abdomen and/or laminated densities at
      the plain abdominal roentgenogram.

PMID- 9577141
TI  - [Duodenal lipoma causing intestinal subocclusion. Case report].
AB  - Duodenum is a rare position for gastrointestinal lipoma which sometimes may lead
      to severe complications. Authors report the case of a 60-year old woman treated
      with a transduodenotomic excision through a midline laparotomy. At admission the
      patient presented epigastric pain for 1 month. Physical examination was negative
      except for a modest epigastric sensitivity. CT scan showed image with regular
      features and fat density, and permitted the exact preoperative diagnosis. Final
      histopathological examination confirmed the diagnosis.

PMID- 9577142
TI  - [Retroperitoneal liposarcoma].
AB  - Retroperitoneal soft-tissue sarcomas are a heterogeneous group of rare and
      peculiar mesenchymal tumors. They are locally invasive and have a peak incidence
      in the fifth decade of life. They account for 0.1-0.2% of all solid tumors and
      15% of all soft-tissue tumors. Liposarcomas are usually large and occur most
      frequently in the lower extremities, in the retroperitoneal, perineal and
      mesenteric region. In the retroperitoneum they grow slowly due to the ability of
      the abdominal cavity to accommodate these slowly expanding masses. They don't
      produce symptoms until they are very large and have invaded local tissues. The
      case of a 61-year old man with a retroperitoneal liposarcoma is reported. The
      tumor was discovered due to the association of abdominal mass, weight loss and
      persistent fever. The fever, especially, is present due to a wide tumor necrosis.
      The diagnosis was suggested by computed tomography. Normally, the interval
      between start of symptoms and diagnosis is included within three weeks and one
      year. Surgical complete resection of the mass with splenectomy and local
      postoperative radiotherapy were performed. The weight of the mass was 8.56
      kilograms and the pathological evaluation showed a pleomorphic highly
      undifferentiated liposarcoma. This histological type normally presents many tumor
      giant cells, some of which have the features of lipoblasts. The single most
      important prognostic factor in patients with soft-tissue sarcomas is the
      histologic grade of the primary lesion. In the last AJCC Staging System the
      grades are assigned from grade 1 (well differentiated) to grade 3 (poorly
      differentiated). The present case is grade 3. In the treatment of sarcoma of the
      retroperitoneum or genitourinary tract, the conventional chemotherapy does not
      seem effective, while radiotherapy has a little improvement on survival. Local
      recurrences are frequent, especially in the first three years, often in the
      absence of distant metastases. When the tumor recurs locally, the best therapy is
      still to remove the mass. Sometimes, two or more operations may be necessary for
      the patient. Generally, the prognosis is poor with overall 5-year survival of 15
      50%. The patient was admitted in our division 4 months after the first operation
      with poor medical condition. The patient died nine months after surgery.

PMID- 9577143
TI  - [Ileal duplication in adults. A very rare nosological entity].
AB  - The report presents a rare case of intestinal duplication in a 43-year old
      female. Intestinal duplication is a rare congenital malformation and is extremely
      exceptional in adults. A lot of etiopathogenic theories have been advanced to
      explain this malformation that can occur anywhere along the alimentary tract,
      even if the ileum remains the most common. It may be cystic or tubular. An
      important aspect of mucosal histology is the possibility of gastric heterotopy,
      conditioning a particular treatment. The literature shows 14 cases with clinical
      very different presentations and instrumental exams were rarely helpful for
      correct diagnosis. Treatment of choice is surgical complete resection of the
      duplication. When contiguous structures are involved intestinal bypass or Roux-on
      Y anastomosis may be necessary with mandatory stripping of the mucosa when
      heterotopic gastric mucosa is present in order to prevent the risk of
      gastrointestinal haemorrhage or malignant transformation, an event possible in
      about 25% of the cases reported in the literature.

PMID- 9577144
TI  - [Volvulus of the sigmoid colon].
AB  - Sigmoid colon is the most frequent side for a volvulus. We present four cases of
      sigmoid volvulus admitted to our department during the period July 1994-December
      1995. Intestinal volvulus, despite its benignity, has a quite high morbidity and
      mortality. Important factors such as the patient's features and frequent late
      diagnosis can influence the complicated outcome of the disease. Plane X-ray of
      the abdomen is helpful while barium enema can be therapeutical because of the
      pressure of the inflated air. Sigmoid resection is the most effective treatment
      for the disease.

PMID- 9577145
TI  - [Acute obstruction of the abdominal aorta].
AB  - The acute occlusion of abdominal aorta is a rare event that may have severe
      clinical results. Personal experience in three cases of acute thrombosis treated
      in emergency surgery are presented. Aorto-iliac thromboendarterectomy, aorto
      bifemoral bypass and thrombectomy with Fogarty catheter were performed. In the
      first case, after the operation, a renal ischemia occurred. The second and the
      third patient died after seven days and twenty-four hours respectively.

PMID- 9577146
TI  - [Venous ulcers of the lower limbs in the aged. Indications for bandages].
AB  - BACKGROUND: There are many causes of ulcer of the lower limb. In the elderly,
      venous ulcers and arteriosclerosis often coexist; for this reason pressure
      bandages might be contraindicated for the risk of precipitating a potentially
      critical arterial flow. In this work, the conditions which allow a safely
      treatment with pressure bandage in the elderly are evaluated. MATERIAL AND
      METHOD: Eleven self-sufficient elderly, with venous ulcerations to one leg only,
      and ankle pressure/omeral pressure between 0.92 and 0.86 were treated with
      elastic bandaging of the leg. RESULTS: All patients completed the treatment, with
      healing of the ulcer obtained in 3-8 months time. So far none of them relapsed.
      CONCLUSIONS: In the elderly, in selected cases, when Pc/Po > 0.86, pressure
      bandages can be safely applied to heal the ulcer, without running the risk of
      endangering arterial circulation.

PMID- 9577148
TI  - [The role of video-laparoscopy in the management of ovarian swellings].
AB  - METHODS: Personal experience in videolaparoscopic treatment of 42 ovarian masses
      during the period September 1991-December 1995 is reported. Seven patients have
      been operated in emergency, 35 in election. Resection of the masses has been
      performed by two methods: dissection and electrocoagulation, generally preferred
      in benign functional cysts; resection by stapler (endo GIA). RESULTS: In 5 of the
      patients operated in emergency an hemoperitoneum was found because of the rupture
      of ovarian cyst; in the other two cases, respectively, a necrotic benign cyst
      twisted on the adnexal axis and a dermoid cyst twisted and necrotic too were
      found. In the 35 patients operated in election, 33 benign cysts, 1 serous
      cystoadenoma 1 granulosa tumour were observed. Postoperative course was always
      excellent, with no painful symptomatology and hospital-stay and convalescence
      extremely reduced (dismission from hospital approx two days after the operation).
      CONCLUSIONS: The different aspects which must be evaluated before choosing mini
      invasive treatment are discussed. An accurate preoperative study especially by
      sonography and serous hormonal dosage (in particular CA 125), besides good
      surgical experience of the operator, are fundamental requisites in order to
      minimize risks of this procedure and guarantee excellent results.

PMID- 9577147
TI  - [Pefloxacin + metronidazole versus netilmicin + metronidazole in the prevention
      of nosocomial infections in contaminated surgery. Pefloxacin Study Group].
AB  - Pefloxacin plus metronidazole versus netilmicin plus metronidazole in the
      prevention of nosocomial infections during contaminated surgery. Surgical
      prophylaxis is widely used in contaminated surgery, especially colorectal
      surgery. In this clinical trial the efficacy of pefloxacin 800 mg i.v. slow
      infusion associated to metronidazole 500 mg i.v. 1-2 hours before surgery and
      then metronidazole alone after 6 and 12 hours versus netilmicin 200 mg i.m.
      associated to metronidazole 500 mg i.v. 1-2 hours before surgery and then both
      after 6 and 12 hours were evaluated in 97 patients suffering by colorectal
      surgery. Efficacy of prophylaxis in patients was evaluated in terms of appearance
      of post-surgical infections (abdominal, urinary, respiratory and wound
      infections). In pefloxacin + metronidazole group (53 patients), two cases of
      wound infections (3.8%) and three cases of respiratory infections (5.8%) were
      observed. In netilmicin + metronidazole group (44 patients), two cases of wound
      infections (4.9%), three cases of urinary infections (7%), three cases of
      respiratory infections (7.5%) and one case of intra-abdominal infection were
      observed. Our data confirmed that in colorectal surgery, the association
      pefloxacin, drug with microbiological and pharmacokinetics characteristics
      suitable for prophylaxis + metronidazole, active against anaerobes pathogens,
      prevents post-surgical infections as well as a reference association (netilmicin
      + metronidazole), with the advantage of a single administration.

PMID- 9577149
TI  - [Antiphospholipid syndrome in obstetrics].
AB  - BACKGROUND: The purpose of this study was to verify the frequency of
      antiphospholipid syndrome in pregnancy associated with fetal wastage and maternal
      hypertension. The antiphospholipid antibody syndrome is a clinical syndrome of
      venous and arterial thrombotic events, recurrent pregnancy loss, and
      thrombocytopenia associated with two autoantibodies: the lupus anticoagulant
      (LAC) and anticardiolipin antibody (ACA). METHODS: A group of 83 pregnant
      patients with recurrent fetal loss or with maternal hypertension for the presence
      of autoantibodies has been studied. None of the patients had systemic lupus
      erythematosus or any other autoimmune disease such as sclerodermia, myasthenia,
      autoimmune thrombocytopenic purpura. The patients have been divided into two
      groups: a) 45 women with fetal wastage history; b) 38 women with maternal
      hypertension. RESULTS: The prevalence of autoantibodies in the first group
      reaches 31.1% (14/45 patients). Two of these 14 patients (14.3%) had fetal loss
      (one with treatment and one without). 12 of this 14 patients (85.7%) had a normal
      delivery and all with treatment. Two treatment scheme were used in this study:
      one with aspirin and another with aspirin and prednisone. In the group of 45
      patients there were 34 normal deliveries: 27 (79.5%) pregnancies were treated
      with aspirin and 7 (20.6%) were treated with aspirin and prednisone. There were
      11 fetal loss and 9 (81.1%) in patients without treatment and 2 (18.2%) in
      treated pregnancies. The prevalence of autoantibodies in the second group reaches
      21%. CONCLUSIONS: In conclusions, it can be suggested that treatment strategies
      for the prevention of fetal loss in the antiphospholipid syndrome are warranted
      because treatment appears to alter fetal outcome favorably.

PMID- 9577150
TI  - [Breast scintigraphy with 99mTc-MIBI in the study of breast cancer].
AB  - BACKGROUND: The literature latest data point out the 99mTc-MIBI scintimammography
      role as a mammography diagnostic complement for a better nosologic definition of
      the breast nodular pathology. The object of this study is to evaluate the device
      sensibility and specificity with reference to the several dimensions of the
      neoplastic nodule. METHODS: A group of 50 patients, with breast nodule has been
      studied comparing scintimammography, mammography, echography and istological
      examination of the removed nodule. RESULTS: 38 nodules out of 50 were carcinomas,
      22 were T1 and 16 T2. As far as scintimammography is concerned, the sensibility
      is 86% in T1 grade and 100% in T2 grade. The specificity is 91.6%. CONCLUSIONS:
      Since the mammography often need integration with invasive examinations,
      (aspiration biopsy, and biopsy) scintigraphy-mammography, global specificity 92%,
      is suggested as a second level examination in the mammary nodule diagnosis, for
      the simple performance and for the little risk for the patient.

PMID- 9577152
TI  - [Use of GnGH (GnRH-A) in gynecology].
AB  - GnRH-agonist therapy is used in the management of many gynaecological
      pathologies: uterine fibroids, endometriosis, ovarian cystic pathology, breast
      cancer, dysfunctional uterine bleeding and, in males, prostatic cancer. In the
      case of uterine fibroids, this therapy can be used as a pre-treatment before
      conservative or demolitive surgery or as an alternative to hysterectomy. At the
      Centre for Therapy of Uterine Pathologies (I Institute of Obstetrics and
      Gynaecology of the University of Rome "La Sapienza") the use of Gn-RH-A therapy
      in uterine fibroids has been investigated and results consistent with those of
      many other groups of study have been obtained. The two most important results
      are: 1. the decrease of both the myoma's size and the uterine volume; 2. the
      block of menometrorrhagiae symptoms, with improvement of the haematic crasis and
      possibility to convert a demolitive surgery to a conservative surgery. GnRH
      agonists can represent a definitive treatment for patients with symptomatic
      uterine fibroids and in perimenopausal age.

PMID- 9577151
TI  - [Effect of hormone replacement therapy on postmenopausal ocular function].
AB  - OBJECTIVE: Determination of the effects of hormonal replacement therapy (HRT) on
      various ocular parameters and symptoms in postmenopausal women. DESIGN:
      Prospective study. SETTING: Department of Obstetrics and Gynecology, University
      "Federico II" of Naples. PATIENTS: 14 healthy women treated orally with equine
      conjugated estrogen in continuous (0,625 mg/daily) and acetate-medroxyprogesteron
      (10 mg/daily) from 17th to 28th day for three months. MEASURES: Ocular
      symptomatology, intraocular pressure (IOP), lacrimal secretion, reflected and
      basal and corneal thickness. RESULTS: After 3 months of HRT the IOP was reduced
      of 10.8% (p < 0.005), the lacrimal secretion, reflected and basal, increased of
      19% and 48%, respectively and the corneal thickness increased of 16.6%.
      CONCLUSION: The HRT has a positive effect on ocular physiology.

PMID- 9577153
TI  - [Experience with non-immunologic hydrops fetalis].
AB  - Non-immune hydrops fetalis (NHF) has become, with the decrease in frequency of
      rhesus-isoimmunization during the last years, an important aspect of modern
      obstetrics in consideration of the increased diagnostic and therapeutic means now
      available. Some cases of NHF with particular etiology (viral twin-twin
      transfusion syndrome, malformations) are reported and the necessity of a
      multidisciplinary specialistic approach for the resolution of diagnostic and
      prognostic problems of this serious complication of pregnancy is underlined.

PMID- 9577155
TI  - [Underestimation of ovarian pathology. Clinical aspects and medico-legal
      considerations].
AB  - In this review are reported the data regarding medical and gynecological
      responsibility in case of underestimation of ovarian pathology compared to
      epidemiological data. It is important to recognize the characteristics of the
      symptomatology, in general very mild, and the diagnostic tests suitable to detect
      ovarian masses. Four steps in the management of ovarian masses which may generate
      errors in the diagnostic and therapeutical process are stressed: the clinical
      diagnosis phase, the surgical phase, the management of borderline tumors, and the
      follow-up. It is also highlighted the importance of the concept of the "delay" in
      the medical action, both diagnostic and therapeutical, and an involvement of the
      Public Health Service, both in the prevention and the treatment of ovarian
      lesions, is ipothesized.

PMID- 9577154
TI  - [Triptorelin therapy in uterine leiomyomatosis. Study of 18 cases].
AB  - BACKGROUND: The validity of tryptoreline treatment in uterine myomatosis is
      demonstrated, both as alternative therapy to surgery in patients in fertile age
      and as preoperative therapy reducing myomatosis volume. MATERIALS AND METHODS: In
      the outpatients department of Gynecologic and Obstetric Institute of the Second
      University of Naples, eighteen women, from 35 to 56 years old, with symptomatic
      uterine myomas, diagnosed by clinical examination and confirmed by pelvic
      ultrasonographic were treated with a delayed-release microcapsule preparation of
      D-Trp-6-LHRH (triptorelin) injected im, every 28 days. The duration of treatment
      was 6 months. RESULTS: The results are statistically significant for 16 patients
      that have completed the therapy with maximal reduction in uterine and leiomyomas
      volumes after 3 months of treatment. Minor side effects such as hot flushes,
      vaginal dryness, headache, dyspareunia were frequently encountered, but they
      disappeared progressively after the end of therapy. CONCLUSIONS: Four months
      after treatment, no significant increase in uterine and myoma volume, was noted.

PMID- 9577156
TI  - [Hypotonic cerebral palsy. Which treatment?].
AB  - BACKGROUND: Aim of this study is to verify whether tonus neurophysiological and
      communicative-relational aspects in hypotonic subjects can be recovered by
      psychomotor therapy. METHODS: This case series includes two randomized groups of
      children with central hypotonia observed at the Department of Child
      Neuropsychiatry of the Gaslini Institute of Genova from February 1992 to December
      1996. The 1st group includes 6 subjects treated in a local rehabilitation service
      only by kinesitherapy. The 2nd group includes 6 children undergoing psychomotor
      treatment in our Department, where all the 12 cases underwent periodical
      controls. RESULTS: Tonus physiological aspects equally improved in the two
      groups, whereas the improvement of the communication aspect was more marked in
      the second. CONCLUSIONS: The conclusion is drawn that psychomotor therapy seems
      more appropriate for a global recovery of the hypotonic child.

PMID- 9577157
TI  - [Cardiac rehabilitation in children. Interdisciplinary approach].
AB  - The concept of rehabilitation has been defined by the authors as a supervised
      process of progressive exercise training to improve aerobic fitness. Cardiac
      rehabilitation in children should be dedicated to patients with repaired complex
      congenital heart diseases who have residual functional and psychological
      problems. The basic objectives for rehabilitation are defined: to improve
      exercise efficiency, aerobic capacity and quality of life, to reduce the
      incidence of sudden death, to enable young patients to take part safely and
      effectively in athletics. The guidelines for organising a cardiac rehabilitation
      programme are specified. First of all the need of protected environments,
      functional evaluation before starting the programme, the description of the
      rehabilitation session and staff needed. Equally important is the psychosocial
      aspect. It is difficult to quantify, in a scientific manner, the effectiveness of
      psychosocial intervention, but it helps the children to integrate into social
      life thus enhancing their quality of life. The results of a census of 110 world
      wide centres offering regular cardiac rehabilitation programmes are presented.
      Italy currently has only two centres suitable for pediatric cardiac
      rehabilitation: they treat a small number of patients. Personal experience, with
      20 patients, agrees with that of Galioto, about an increase in exercise capacity
      of these patients after rehabilitation programme, with an increased cardiac
      output at rest and at peak of exercise, an increased O2 uptake and an increased
      duration of exercise testing. The usefulness of cardiac rehabilitation
      programmes, the need of interdisciplinary approach and increasing the case series
      are stressed.

PMID- 9577158
TI  - [Acute scrotal involvement as onset of a testicular Sertoli cell tumor in a two
      month-old baby].
AB  - Sertoli cell tumour is an uncommon neoplasm, either in the adult and in the
      pediatric age groups. An intrascrotal, slowly growing, painless swelling
      generally represents its clinical onset. Orchiectomy definitively is successful
      in these patients, since Sertoli cell tumour very rarely metastatise elsewhere.
      The case of a two-month old baby in which an acute intrascrotal involvement
      (requiring immediate surgical therapy), was the atypical onset of a testicular
      Sertoli cell tumour, is described. The hystogenesis as well as the clinical and
      pathological peculiarities of this neoplasm in pediatric patients are discussed.

PMID- 9577159
TI  - [Purpura fulminans in the newborn. Report of two cases successfully treated with
      heparin and antithrombin III].
AB  - Purpura fulminans is a rare form of disseminated intravascular coagulation
      characterized by rapidly progressive purpuric lesions, hypotension and, in some
      cases, fever. In neonates, purpura fulminans usually develops following
      deficiency of anticoagulant protein C or S, although acquired forms have been
      described. The management of disseminated intravascular coagulation is still
      controversial, with some studies finding a positive effect of anticoagulants and
      others showing no effect or even a detrimental one. Therefore, at present,
      management is limited to the treatment of underlying disease and replacement of
      clotting factors. Personal experience is reported on the efficacy of heparin in
      combination with antithrombin III in the treatment of purpura fulminans in two
      preterm neonates who did not have inherited deficiency of protein C or S and
      developed the disease possibly following prolonged labor (36 hours) in the first
      case, and maternal neoplasia, in the second. Both neonates presented with
      widespread cyanotic areas rapidly evolving in purpuric lesions and hemorrhagic
      bullae. Laboratory tests (prolonged prothrombin and partial thromboplastin time,
      fibrinogen and antithrombin III concentrations below normal ranges, d-dimer
      highly positive) were consistent with disseminated intravascular coagulation. In
      both cases anticoagulant treatment with heparin (50 UI/kg in bolus followed by 15
      UI/kg/h) and antithrombin III was associated with resolution of disseminated
      intravascular coagulation and prompt amelioration of the purpuric lesions,
      without apparent side effects.

PMID- 9577160
TI  - [Treatment of atopic dermatitis with oxatomide oral suspension (2.5 mg/ml) in
      infants].
AB  - BACKGROUND: The aim of the present trial is to determine the efficacy and safety
      profile of oxatomide, a potent antiallergic drug, in children aged under 2 years,
      suffering from atopic dermatitis. A comparison between 2 different dosage schemes
      was scheduled. METHODS: An oral suspension of oxatomide, in a neonatological
      formulation at a low dosage (2.5 mg/mL) was administered to 20 children in the
      following manner: 1 mg/kg/day in a single evening dose (9); 0.5 mg/kg every 12
      hrs (11) for a period of 60 days. Cutaneous symptoms were assessed at the
      baseline, and after 15, 30 and 60 days. All adverse events were recorded in
      detail. RESULTS: After 15 days, at both doses, oxatomide significantly reduced (p
      < 0.05 vs baseline) atopical symptoms: itching, crusting, lesions due to
      scratching and after 30 days erythema and papulovesicles. No statistically
      significant differences were observed in terms of efficacy between the two dosage
      schemes, although oxatomide in a single dose led to a slightly faster
      improvement. Oxatomide displayed an excellent therapeutic safety profile.
      CONCLUSIONS: The results show that oxatomide in a low-dosage formulation is a
      good antiallergic drug, effective and safe in a specific population which is
      extremely delicate, such as children under 2 years old.

PMID- 9577161
TI  - [Syndrome of right bundle branch block, ST segment evaluation from V1 to V3 and
      sudden cardiac death].

PMID- 9577163
TI  - [Optimization of thrombolytic treatment in acute myocardial infarct: the role of
      new fibrinoselective drugs and their combination with new antithrombotics].
AB  - Although reperfusion therapy is well recognized as the mainstay of treatment of
      acute myocardial infarction, mortality of myocardial infarction is still high,
      thrombolytic treatment remains underutilized and, usually, applied too late.
      Additionally, most of the patients do not experience optimal reperfusion because
      of the suboptimal flow rate in the infarct-related artery, abnormal microvascular
      flow, and reocclusion of the infarct-related artery. Strategies to enhance the
      results of reperfusion therapy include, expanding the population of potential
      candidates, earlier treatment, and newer methods to improve infarct-related
      artery flow rates. In this sense, new thrombolytic agents, and combination
      therapies with or without addition of more potent and specific new antithrombotic
      agents are being extensively investigated. Also, it is important to promote
      studies of ancillary treatments to reduce reperfusion injury, which may be one
      cause of decreased microvascular flow. Although aspirin and heparin have been the
      conventionally used agents for inhibiting thrombin and platelet function, newer
      agents such as hirudin or hirulog and inhibitors of the platelet glycoprotein IIb
      IIIa receptors are becoming available, and their clinical application will
      increase in the future.

PMID- 9577162
TI  - [Thrombosis and coronary disease: neutrophils, nitric oxide and aspirin].
AB  - In recent years, relevant changes have occurred in the knowledge of the cellular
      mechanisms regulating platelet aggregation and adhesion to the endothelial
      surface. In particular, major aspects of the interactions between platelets and
      endothelial cells and neutrophils have been clarified. These interactions involve
      not only thrombosis-promoting or thrombosis-inhibiting properties but also
      several aspects of the regulation of vascular function. A new concept has
      progressively emerged showing thrombosis as a multicellular event in which cell
      to cell interactions between platelets, neutrophils, and endothelium regulate the
      size of a growing thrombus. In brief, there is consistent evidence showing that
      two vasodilating mediators produced by endothelial cells and neutrophils (nitric
      oxide and prostacyclin) have antiaggregating platelet effects. Platelet
      activation is particularly relevant in myocardial ischemia, and several
      pharmacological strategies have been devised to prevent intravascular platelet
      activation. Aspirin remains a keystone of these preventive and damage-limiting
      strategies. Current knowledge maintains that low doses of aspirin decrease in
      vivo platelet aggregation by a selective inhibitory effect on thromboxane A2
      production by platelets with maintenance of prostacyclin production by the
      endothelium. We have recently focussed our research on the basis that the
      antiaggregating effect of aspirin could be explained not only by the above
      mentioned effects on thromboxane A2 synthesis, but also through its action on
      neutrophils. Our in vitro and ex vivo studies have demonstrated that neutrophils
      enhance the antiaggregating effects of acetylsalicilic acid on platelets. We have
      shown that acetylsalicilic acid stimulates nitric oxide production on neutrophils
      inhibiting the aggregating effects of thrombin, ADP or epinephrine on platelets.
      the role of the neutrophils in ischemic events enhancing the tissue damage
      through the release of several proteases, reactive oxygen species and tumor
      necrosis factor-alpha has been extensively demonstrated. In an experimental model
      of acute ischemia/reperfusion in rabbits, we have shown that acetylsalicilic acid
      is able to enhance the nitric oxide production by neutrophils providing a
      potential mechanism for the beneficial action of aspirin in the myocardial
      infarction. Further research is needed to assess the mechanisms of the action of
      aspirin during the thrombotic phenomena and its effects on the different types of
      cells that compound the microvascular environment.

PMID- 9577164
TI  - [From the ivory tower to the trenches. Procosity come to the coronary unit].

PMID- 9577165
TI  - [MIBI-echocardiography with dobutamine: Significance of changes of contractility
      in patients with changes in perfusion].
AB  - BACKGROUND AND OBJECTIVES: In the presence of coronary artery disease and with an
      appropriate stressor, perfusion defects precede contractility abnormalities.
      Perfusion defects without contractility abnormalities may be due to the absence
      of ischemia or mild ischemia. Our purpose has been to compare the clinical
      characteristics, hemodynamic response and severity of perfusion defects in
      patients with coronary artery disease and perfusion defects with and without wall
      motion abnormalities during dobutamine infusion. PATIENTS AND METHODS: Eighty two
      patients with significant coronary artery disease demonstrated by angiography
      without previous myocardial infarction underwent dobutamine infusion (up to 40
      mg/kg/min). Atropine was given when necessary. Stress scientigraphic MIBI-SPECT
      images were acquired 1 hour after peak stress and rest studies were obtained 24
      hours after stress testing. The perfusion score was calculated by dividing the
      total uptake score between the number of segments affected. RESULTS: Among the 73
      patients with perfusion defects, stress echocardiography was positive in 59
      (Group A) and was negative in the remaining 14 (Group B). There were more
      hypertensive patients in Group A (33 vs 4; p = 0.04). There was no significant
      difference between the two groups with respect to other clinical characteristics.
      The peak rate-pressure product was similar in both groups (18.520 +/- 5.691 vs
      18.680 +/- 5.329; p = NS). The development of electric abnormalities and angina
      was more common in Group A (42 vs 3, p < 0.001 and 33 vs 1; p < 0.001). Perfusion
      defects were not more extensive in Group A (abnormal segments 2.15 vs 2.21; p =
      NS) but they were more severe (segments with severe uptake reduction or no uptake
      1.10 vs 0.28; p < 0.05; perfusion score 2.62 vs 2.21; p < 0.05). CONCLUSION: In
      patients with severe coronary artery disease and perfusion defects during
      dobutamine-MIBI-SPECT, the presence of wall motion abnormalities defines patients
      with more severe perfusion defects.

PMID- 9577166
TI  - [The value of exercise echocardiography in the diagnosis of coronary disease in
      patients with left heart branch block in the bundle of His].
AB  - OBJECTIVE: To assess the diagnostic value of exercise echocardiography in
      patients with complete left bundle branch block and clinical suspicion of
      coronary artery disease. MATERIAL AND METHODS: Among 1,176 exercise
      echocardiograms performed from May of 1994 to November of 1996, 92 showed
      complete left bundle branch block in the resting electrocardiogram. We
      retrospectively analyzed data of 23 patients who had coronary angiography
      performed within 6 weeks of the exercise echo (19 males and 4 females, age 62 +/-
      8, resting ejection fraction 52 +/- 10%). Previous acute myocardial infarction
      was demonstrated in 8 of them. The development of new or worsening regional
      dysfunction was considered an ischaemic response on exercise echo; whereas we
      assumed that there was significant coronary artery disease on the coronariography
      whether there was > or = 1 vessel disease in patients without previous myocardial
      infarction or > or = 2 vessel disease in patients with previous infarction.
      RESULTS: Ten patients showed multivessel disease (> or = 2 vessels, 6 with
      previous infarction); 5 one-vessel disease; and 8 non significant coronary artery
      disease. Exercise echocardiography sensitivity for ischaemia detection in the
      entire group was 86% (95% confidence interval 67-100%); the specificity was 67%
      (36-98%), predictive value of a positive test was 80% and predictive value of a
      negative test was 75%. Sensitivity for the detection of > 50% stenosis in the
      left anterior descending coronary territory was 92% (76%-100%) and specificity
      64% (35%-92%); for right coronary artery sensitivity was 80% (55%-100%) and
      specificity 77% (54%-100%); and for left circumflex artery sensitivity was 70%
      (42%-98%) and specificity 69% (44%-94%). CONCLUSIONS: Exercise echocardiography
      may be useful in the evaluation of patients with left bundle branch block and
      clinical suspicion of coronary artery disease; with good sensitivity and low
      specificity.

PMID- 9577167
TI  - [Long term follow-up in patients with the permanent form of junctional
      reciprocating tachycardia treated with radiofrequency ablation].
AB  - OBJECTIVES: This study sought to determine the long-term follow-up, safety and
      efficacy of radiofrequency catheter ablation in patients with the permanent form
      of junctional reciprocating tachycardia. We assessed the reversibility of
      tachycardia-related left ventricular dysfunction and we detailed the location and
      electrophysiologic characteristics of these atrioventricular decremental
      pathways. BACKGROUND: Permanent junctional reciprocating tachycardia is an
      infrequent form on reciprocating tachycardia, commonly incessant and usually drug
      refractory. The electrocardiographic hallmarks include an RP interval > PR with
      inverted P waves in leads II, III, aVF and V3-V6. During tachycardia, retrograde
      ventriculo-atrial conduction occurs over an accessory pathway with decremental
      conduction properties, located predominantly in the posteroseptal zone. It is
      known that long lasting and incessant tachycardia may result in tachycardia
      related severe ventricular dysfunction, the so called tachycardiomyopathy.
      PATIENTS AND METHODS: We included 24 patients (9 males, 15 females; mean age 42
      +/- 22 years) with the diagnosis of permanent junctional reciprocating
      tachycardia at electrophysiologic study. Six patients had tachycardia-related
      left ventricular dysfunction. Radiofrequency energy was delivered at the site of
      earliest retrograde atrial activation during reciprocating tachycardia (n = 22)
      or ventricular pacing (n = 2). All patients were followed at the outpatient
      clinic and serial echocardiograms were performed in those who presented depressed
      left ventricular function. RESULTS: Radiofrequency catheter ablation was
      performed in 24 decremental accessory pathways. Earliest retrograde atrial
      activation was right posteroseptal in 22 patients (92%), right midseptal in 1
      (4%) and right posterolateral in 1 (4%). Twenty-three accessory pathways were
      successfully ablated with a mean of 5 +/- 3 (median, 4) radiofrequency
      applications of a mean duration of 48 +/- 13 s. Only the midseptal accessory
      pathway could not be ablated. After a mean follow-up of 21 +/- 16 months (median,
      15; range 2 to 64) 22 patients remain asymptomatic. There were recurrences in 4
      patients after the initial successful ablation (three during the first month and
      one during the second month after the procedure), two were ablated in a second
      ablation procedure, one patient required a third procedure and one required a
      fourth. All patients with left ventricular dysfunction experienced an improvement
      after ablation. Mean preablation left ventricular ejection fraction in patients
      with tachycardiomyopathy was 28 +/- 6% (median, 27) and raised to 51 +/- 16%
      (median, 47) after ablation (p < 0.02). CONCLUSIONS: Our study supports the
      concept that radiofrequency catheter ablation is a safe and useful treatment for
      patients with permanent junctional reciprocating tachycardia. Radiofrequency
      current should be the treatment of choice in these patients because this
      arrhythmia is usually drug-refractory. The majority of accessory pathways with
      decremental conduction properties are localized in the posteroseptal zone.
      Cessation of the arrhythmia after successful ablation results in recovery of left
      ventricular dysfunction.

PMID- 9577168
TI  - [Initial results with the Multi-Link coronary stent].
AB  - INTRODUCTION AND OBJECTIVES: The Multi-Link intracoronary stent is a balloon
      expandable stainless steel stent with an interconnected ring structure designed
      to provide a high degree of compressive resistance while preserving longitudinal
      flexibility. We present the results of our initial experience with the
      implantation of this stent. PATIENTS AND METHODS: From May 1996 to April 1997,
      124 Multi-link stents were implanted in 97 patients. Mean age 62.2 +/- 11 years.
      All patients included had a coronary artery diameter > 2.7 mm. Clinical
      presentation includes stable angina in 20, unstable angina in 72, and myocardial
      infarction in 5 patients. According to the ACC/AHA classification 6 lesions were
      type A, 72 type B and 19 type C. The implantation of the stent was for "de novo"
      lesions in 85 patients and for restenosis in 12. Patients were treated after the
      procedure with a combination of aspirin and ticlopidine, except six of them who
      received aspirin and acenocumarol. 16 patients were treated additionally with
      Abciximab. The degree of stenosis was determined by quantitative angiography.
      RESULTS: The delivery of the stent was successful in all patients. The degree of
      stenosis before the procedure was 79.6 +/- 13.1%, and after the stent deployment
      was 17.7 +/- 11.4%. Three patients presented a non-Q-wave myocardial infarction,
      two patients had a subacute stent thrombosis, one of them died due to heart
      failure. During a follow-up of 4.7 +/- 2.6 months five patients were readmitted
      with recurrent angina (4 due to restenosis and one for vessel occlusion) and one
      patient with heart failure after myocardial infarction died suddenly three weeks
      after the dilatation. CONCLUSIONS: The Multi-Link stent was implanted
      successfully in all patients with a low incidence of complications, showing at
      the follow-up a reduced rate of clinical restenosis.

PMID- 9577169
TI  - [Pathology of diseases of extracardiac origin. VI. Disease of the connective
      tissue and heart].
AB  - Connective tissue diseases encompass a wide group of nosologic entities of
      unknown etiology, characterized by multisystemic organ involvement, sharing an
      immunologic pathogenetic mechanism, producing a variety of inflammatory
      manifestations, and whose primary lesion is always a diffuse vasculitis. Any part
      of the cardiovascular system may be involved, including the pericardium, the
      myocardium, the endocardium and valves, the coronary arteries, the aorta, the
      pulmonary vasculature, the peripheral arteries, veins, arterioles, venules, and
      the capillary beds of almost every organ subsystem. Pathologic studies disclose a
      high prevalence of heart involvement, but the presence and extent of pathologic
      findings correlate poorly with clinical manifestations. With the advent of
      echocardiography-Doppler, milder and earlier cases are now recognized. Although
      these patients continue under the care of rheumatologists and internists, when
      cardiac involvement arises, cardiologists must be aware of the characteristics,
      outcome and management of connective tissue diseases.

PMID- 9577170
TI  - [Bacterial endocarditis in the aortic valve of a three month old infant.
      Correction with an aortic homograft].
AB  - We report the case of a three-month-old infant with an infective endocarditis of
      the aortic valve, showing perforation of two valve leaflets and a perivalvular
      abscess. The patient was operated on using a cryopreservated homograft with
      anastomosis of both coronary arteries. The outcome is good two years after
      surgery. This is the youngest patient operated on using this technique in our
      country.

PMID- 9577171
TI  - [Effectiveness of exercise echocardiography in the diagnosis of left bundle
      branch block. A case report].
AB  - A left bundle branch block is very often suggestive of cardiac diseases. Left
      bundle branch block is also present with angina in patients with normal coronary
      arteries. We report a case of a man with a left bundle branch block in which the
      most effective, rapid and economic method of diagnosis was exercise
      echocardiography. Different diagnostic techniques are discussed and compared.

PMID- 9577172
TI  - [Uncommon atrial flutter related to cicatrix from atriotomy surgery:
      radiofrequency catheter ablation].
AB  - A patient with a complex congenital abnormality required the implantation of an
      interatrial septum patch through a right lateral atriotomy. Nine years later he
      developed two different morphologies of an incessant uncommon atrial flutter
      refractory to antiarrhythmic drug treatment. The electrophysiological study
      localized a site on the right atrium lateral wall where local activation time was
      75 ms earlier than the onset of the P wave, transient entrainment with concealed
      fusion was obtained, the first postpacing interval after transient entrainment
      was 5 ms longer than tachycardia cycle length and the stimulus to P wave interval
      was 50 ms. At this site, radiofrequency delivery terminated the atrial flutter in
      less than 1 second. No further induction or recurrences of any morphology of the
      atrial flutter were observed after a four month follow up. These findings suggest
      the existence of a narrow conduction isthmus amenable to interruption by focal
      delivery of radiofrequency. The isthmus was most probably located between the
      atriotomy and the crista terminalis, posterior to the former and anterior to the
      latter.

PMID- 9577174
TI  - [Radiofrequency catheter ablation of accessory pathways in an infant tuberous
      sclerosis and cardiac rhabdomyoma].
AB  - Rhabdomyomas may be the underlying cause of accessory pathways in patients with
      tuberous sclerosis, leading to symptomatic supraventricular tachycardia that does
      not respond to antiarrhythmic drugs. We report an infant with tuberous sclerosis
      and cardiac rhabdomyomas who underwent successful radiofrequency catheter
      ablation of a left free wall accessory pathway and we describe the clinical
      features, ablation findings and long-term follow-up.

PMID- 9577173
TI  - [Idiopathic left ventricular tachycardia in infancy: long-term control with
      verapamil].
AB  - Idiopathic verapamil-responsive left ventricular tachycardia is an uncommon
      arrhythmia in childhood. Although this tachycardia is usually responsive to
      verapamil, non-pharmacologic therapy may be necessary in the long-term follow-up.
      We report a thirty-four month old child with incessant left ventricular
      tachycardia refractory to digoxin and amiodarone. The diagnosis was confirmed by
      electrophysiologic study. Intravenous verapamil successfully controlled the
      arrhythmia. On oral verapamil, the patient remains asymptomatic over a follow up
      period of 7 years and 10 months.

PMID- 9577175
TI  - [Priority of using conventional cytogenetics, in situ hybridization and PCR in
      the study of hematologic neoplasms].

PMID- 9577176
TI  - [Usefulness of molecular screening in childhood lymphoblastic leukemias].
AB  - PURPOSE: To demonstrate that a molecular screening by reverse transcriptase
      polymerase chain reaction (RT-PCR) of TEL/AML1, E2A/PBX1 and BCR/ABL genes in
      pediatric acute lymphoblastic leukaemia is a rapid method that allows one to
      exceed the percentage of adult patients with the BCR/ABL rearrangement. PATIENTS
      AND METHODS: 12 Spanish children with acute lymphoblastic leukaemia were studied,
      11 of them newly diagnosed and 1 relapsed. The patients were between 18 months
      and 10 years old. Bone marrow aspiration was collected between april and december
      1996, RNA was isolated and cDNA was subjected to PCR amplification for TEL/AML1,
      E2A/PBX1 and BCR/ABL genes. Normal ABL and E2A genes were studied as
      amplification controls. RESULTS: One of these hybrid genes was found in 33.3% of
      patients studied. TEL/AML1 in two cases (16.6%), E2A/PBX1 in one case (8.3%) and
      BCR/ABL in another one (8.3%). CONCLUSIONS: On the basis of these data it would
      be useful to achieve a molecular screening of TEL/AML1, E2A/PBX1 and BCR/ABL
      genes in pediatric acute lymphoblastic leukaemia for allowing a molecular
      classification in a great percentage of patients that exceed the BCR/ABL
      positivity in adults.

PMID- 9577177
TI  - [Interference in blood coagulation tests on lipemic plasma. Correction using n
      hexane clearing].
AB  - PURPOSE: To eliminate the bias in the plasmatic coagulation test caused by
      lipemic samples by means of with addition of n-hexane in the ACL-3000 analyzer
      (Instrumentation Laboratory). MATERIAL AND METHODS: The turbidity caused by
      lipemia was simulated by addition of increasing quantities of Intralipid 20%
      (interferent) to samples from patients with normal pathological coagulation tests
      (with oral anticoagulant therapy). We compared the results of PT (prothrombin
      time), fibrinogen (derived) and APTT (activated partial thromboplastin time)
      before and after the addition of n-hexane. RESULTS: In samples with an elevated
      concentration of interferent (> 9.79 mmol/L of triglycerides) the analyzer failed
      to give any results. Once the lipids were cleared by n-hexane, the analyzer
      offered results for all the samples, which coincided with the original sample
      after applying a correction factor 1.06 to the TP and 0.88 to the TTPA.
      CONCLUSION: The addition of n-hexane is a valid method to eliminate the bias
      caused by the lipids in the coagulation tests.

PMID- 9577178
TI  - [Evaluation of the polyethyleneglycol antiglobulin test in the detection and
      identification of erythrocyte antibodies].
AB  - PURPOSE: The polyethylene glycol antiglobulin test has been found to enhance the
      reactivity of most alloantibodies. MATERIAL AND METHODS: To investigate the
      utility of polyethylene glycol antiglobulin test for detection and identification
      of red blood cell antibodies, a comparison study of polyethylene glycol (PEG), a
      low-ionic-strength additive solution (LISS) and bovine serum albumin (BSA) was
      conducted. The sera of 47 different patients with positive antibody screening
      test by the LISS method, were tested in parallel with reagent antibody-detection
      cells using PEG, LISS and BSA. RESULTS: In the sera of 47 patients, 57 antibodies
      were detected. We identified 39 antibodies by the three methods. Twelve
      antibodies reacted by the BSA method and the LISS method but did not react with
      the PEG method (8 anti-I, 1 anti-P1, 1 anti-Lea(a), and two antibodies missed by
      the PEG method because they did not react with anti-IgG: 1 anti-M and 1 anti-K).
      Three antibodies reacted only with the LISS method (3 anti-I). Four clinically
      significant antibodies were detected only by the PEG method (2 anti-Jka, 1 anti
      Jkb, 1 anti-c). The serum from a patient with delayed hemolytic transfusion
      reaction and no antibody detectable by the LISS and the BSA methods was tested by
      the PEG method. We were able to detect an anti-Jka by PEG in the pretransfusion
      sample. In 24 (60%) of 40 samples with clinically significant antibodies, PEG
      antiglobulin reactions were stronger (total score 221) than LISS antiglobulin
      reactions (total score 170) and BSA antiglobulin reaction (total score 184); in
      14 (35%) of 40 samples, they were identical, and in 2 (5%) agglutination in the
      PEG method was weaker. CONCLUSION: In our experience, the polyethylene glycol
      antiglobulin test is more sensitive than LISS and BSA in detecting clinically
      significant antibodies and is an acceptable technique for routine compatibility
      test.

PMID- 9577179
TI  - [Correlation of flow and static cytometry; their application to the study of
      anaplastic lymphomas].
AB  - PURPOSE: DNA study by cytometric methods is one of the prognosis factors
      considered in malignant tumours. Flow cytometry (FCM) was the most frequently
      used techniques in cell suspensions. Image cytometry (ICM) was also applied in
      cellular smears and it is possible to measure the results with an Image Analyzer,
      which supposes a substancial advantage over DNA studies. To confirm the results
      and correlation of the two techniques a controversial subtype of lymphoid tumour
      was selected: Anaplastic large cell lymphoma (ALCL). MATERIAL AND METHODS: Fifty
      four cases of ALCL (23 classical type and 31 ACL-Hodgkin related) were studied.
      Cytometry was performed in paraffin-embedded tissues previously dewaxed,
      rehydrated and minced. FCM was done in suspensions incubated with ribonuclease A
      and stained with propidium iodide in an EPICS-C flow cytometer. ICM study was
      performed in Feulgen-stained smears and measured by an Image Analyzer CAS-200.
      RESULTS: All cases were aneuploid. ALCL were 30.5% hypodiploid (HpD) and 69.5%
      hyperdiploid (HrD) by FCM; 43.5% HpD and 56.5% HrD by ICM. ALCL-HR were 58% HpD
      and 42% HrD by FCM; 68% HpD and 32% HrD by ICM. There was a lack of correlation
      of 22% between both methods but it was not statistically significant.
      CONCLUSIONS: We can conclude the obtained results by FCM and ICM are almost
      similar.

PMID- 9577181
TI  - [Moderate hyperhomocysteinemia: physiopathology of the endothelial lesion and its
      clinical implications].

PMID- 9577180
TI  - [Evaluation of the quality of prothrombin time technique in the Basque Country].
AB  - PURPOSE: The Programme for Quality Assessment in Anticoagulant Therapy, which was
      started in the Basque Country in 1984, included the manufacturing of a standard
      human thromboplastin reagent plus periodical quality controls of the prothrombin
      time. A rabbit thromboplastin reagent was available in 1994; it was called
      Thromboplastin Bilbao, or TBi, and had to be used as a pattern reagent. Its
      stability, sensitivity and composition were plotted against the Manchester
      Reagent, of similar nature and composition. A new phase of quality quality
      controls was simultaneously started with this new reagent, a group of hospitals
      of the Autonomous Community taking part in the programme. The aim was to compare
      this reagent with the others used by the hospitals and to evaluate the variations
      with regard to the stages previous to the introduction of the human reagent.
      MATERIAL AND METHODS: Nine centres joined the study. Controls were performed
      every fourth month including plasma from patients under anticoagulant treatment,
      plus the reference reagents. The partaking centres used their usual reagents and
      routine procedures, as well as the reference reagents and manual technique.
      RESULTS: The coefficient of variation (CV) of the INR of anticoagulated plasmas
      used for these studies when following the centres' own methods and
      thromboplastins was 9.5 +/- 6.40%, versus 9.94 +/- 1.57% when TBi was used. These
      results are in accordance with those attained with the previously manufactured
      human reagent, whose CV was 8.75 +/- 2.19% in the quality assurance methods
      performed in the period 1984-88. Concurrently with the programme, the reagent was
      sent as a part of the Spanish Programme for Quality Assessment in Anticoagulant
      Treatment to the 51 centres taking part in the study. The CV of the INR of the
      two lyophilized plasmas sent was, respectively, 14.97% and 16.5%. The average
      value for the healthy subjects was 14.77 seconds, with 8% inter-centres variation
      when using manual methods. CONCLUSIONS: These results suggest that a
      thromboplastin is now available whose sensitivity and reproducibility make it
      suitable as the national standard for usage in the quality assessment of
      prothrombin time.

PMID- 9577182
TI  - [Congenital dyserythropoietic anemia morphologically type I with a positive
      HEMPAS phenomenon].
AB  - A patient with clinical and morphological anaemia of type I is described.
      Surprisingly, the Ham's test yield positive with 2 of 20 compatible serum. Only
      other such case is recorded in the literature. We revised the literature and
      comment the unclassified cases reported.

PMID- 9577183
TI  - [Application of the polymerase chain reaction to the diagnosis of sickle cell
      anemia in Venezuela].
AB  - Application of polymerase chain reaction technology to detect sickle cell
      patients and heterozygous carriers in a group of patients suspect for sickle cell
      disease was carried out. The sample was composed of 102 normal individuals, and
      102 unrelated out patients who were attending in the Hematology Service at the
      Maracay Central Hospital in the State of Aragua in Venezuela. All patients were
      interviewed. Results of their medical histories and the physical examination,
      made during the clinical visit, were recorded. The blood samples were collected
      in EDTA by venopuncture and genomic DNA was extracted from leucocytes. An
      amplified 536 base pairs fragment of the beta-globin gene containing codon 6, was
      digested with an isoschizomer of Mst II, Bsu36 I and electrophoresed in 3%
      agarose. We have established the technical conditions in our laboratory for the
      detection of sickle cell disease using a PCR assay. 32 patients having
      haemoglobin SS (HbSS) and 70 patients in the heterozygous state (HbAS) were
      identified. We confirm that the normal controls have the HbAA genotype. The
      standardization of a highly sensitive and specific diagnostic test for sickle
      cell disease permited us to identify the normal controls, the homozygotes and
      heterozygotes. This methodology is one of the fundamental technical bases for
      establishing a newborn screening programme in the Central Region of Venezuela and
      also has application in research related with other genetic diseases that affect
      the Venezuelan people.

PMID- 9577184
TI  - Pure red cell aplasia due to persistent B19 parvovirus infection in patient
      infected with human immunodeficiency virus type 1. Recovery with alpha-interferon
      therapy.
AB  - B19 parvovirus (PV) infection is ordinarily resolved with the production of
      specific antibodies that neutralize virus infectivity for erythroid host cells.
      Nevertheless persistent infection with B19 PV and pure red blood cell aplasia
      have been documented. A 27 year-old male. i.v. drug abuser, HIV+ and HCV was
      diagnosed of pure red cell aplasia. Six months later we had serologic evidence of
      persistent parvovirus infection. Interferon therapy, started for HCV infection,
      showed a marked improvement of anaemia and anti parvovirus IgM became negative.
      It is discussed the possible role of interferon therapy in persistent parvovirus
      infection.

PMID- 9577185
TI  - [Blood preservation. Bacteriological, immunohematological, hematological and
      hemorrheological studies].
AB  - The knowledge of erythrocyte viability during blood bank storage period has been
      a major problem for transfusional practice. This problem must be considered by
      taking into account blood flowing properties which are directly related to the
      rheological properties of erythrocytes. The aim of this work was to perform an
      interdisciplinary study of the modifications induced in erythrocyte properties
      during 29 days storage of whole blood in a blood bank. Three samples of venous
      blood collected from healthy adults in plastic bags, anticoagulated with ACD
      (citric acid, citrate, dextrose) and stored at 4 degrees C were studied.
      Rheological properties (deformability, membrane elasticity and surface
      viscosity), immunohematological conditions (antigenicity) of erythrocytes,
      haematological index variation and bacteriological cultures of blood were weekly
      analysed. Rheological studies were performed using the Erythrodeformeter, a
      polymicroviscosimeter (paper filter) and erythrocyte filtration through
      polycarbonate membranes of 5 microns pore diameter. Impairment of membrane
      rheological properties, loss of antigenicity and decreases of Ht, Hb, MCHC and
      MHC were observed. Bacteriological cultures gave always negative results. The
      studies performed showed significant alterations of erythrocyte rheological
      parameters. It becomes evident that such modifications would influence the
      erythrocyte mechanical behavior in microcirculation and impair the in vivo
      viability of the transfused red cells.

PMID- 9577186
TI  - [Contribution of magnetic resonance to the differential diagnosis of a collapsed
      vertebra in a patient with multiple myeloma].
AB  - The only safe method to determine whether or not patients diagnosed of smoldering
      myeloma will progress to symptomatic multiple myeloma (MM) is periodic follow-up.
      In the last years, several studies have emphasized the efficacy of magnetic
      resonance imaging (MRI) to detect bone marrow involvement in these patients.
      However, the detection of a focal spinal lesion in elderly patients raises a
      diagnostic problem, sometimes difficult to solve, between a benign or malignant
      origin. We present the case of an elderly women with marked osteoporosis and
      smoldering myeloma who suddenly complained of pain in dorsal spine. MRI showed
      focal lesions in two dorsal vertebra consistent with myeloma involvement.
      However, there were no other signs of progression, the lesions were considered
      secondary to osteoporosis and calcitonin was administered. This resulted in the
      disappearance of the pain and the MRI abnormalities, which confirmed its benign
      etiology. The role and limitations of MRI to detect bone marrow involvement by MM
      in the evaluation of these patients is reviewed.

PMID- 9577187
TI  - [Semiology of the exploration of residual masses in the mediastinum using imaging
      techniques].

PMID- 9577188
TI  - [Standardization Committee of the Spanish Society for Hematology and Hemotherapy:
      a contribution to the quality of the hematology laboratory].

PMID- 9577189
TI  - [Ultrapure factor VIII concentrate with double virus inactivation: study of
      pharmacokinetics in von Willebrand's disease patients].

PMID- 9577190
TI  - [Intensive treatment of T-cell-rich B lymphoma].

PMID- 9577191
TI  - [Relation of benign lymphoid hyperplasia and malignant lymphoma. Apropos of a
      case].

PMID- 9577192
TI  - [Myeloma with extramedullary extension coinciding with the normalization of serum
      paraproteins after treatment].

PMID- 9577193
TI  - [Guillain-Barr+e syndrome after autologous bone marrow transplantation].

PMID- 9577194
TI  - [Bacteremia caused by Agrobacterium radiobacter].

PMID- 9577195
TI  - [Contamination by Serratia marcescens of a unit of packed red blood cells].

PMID- 9577196
TI  - [Evaluation of the treatment used in a case of autoimmune hemolytic anemia using
      the erythrophagocytosis functional test].

PMID- 9577197
TI  - [The reality concerning approval of specialty degrees in the European Union].

PMID- 9577198
TI  - [Cutaneous manifestations of hepatitis C virus].

PMID- 9577199
TI  - [Local-regional anesthesia in ambulatory surgery].

PMID- 9577200
TI  - [Sinus heart rate variability after a myocardial infarction].

PMID- 9577201
TI  - [Coronary artery surgery, analysis of prognostic factors: 243 cases].

PMID- 9577202
TI  - [Mortality and cause of death in an internal medicine service].

PMID- 9577203
TI  - [Evaluation of blood product transfusion in surgery intensive care].

PMID- 9577204
TI  - [Prognostic factors in pregnancy toxemias].

PMID- 9577205
TI  - [Hospital infections. Study of positive bacterial case prevalence --University
      Hospital Center of Sahloul (1992-1996), Sousse, Tunisia].

PMID- 9577206
TI  - [Intra-cortical diaphyseal Brodie abscess of the long bones. Four cases].

PMID- 9577207
TI  - [Ocular-orbital complications from radiotherapy. Two case reports and literature
      review].

PMID- 9577208
TI  - [Neurofibroma of the posterior bladder wall (a case report)].

PMID- 9577209
TI  - [Costal lysis caused by pulmonary histiocytosis X].

PMID- 9577210
TI  - [Eight cases of psoas abscess at the University Hospital Center of Lome-Tokoin,
      retrospective study].

PMID- 9577211
TI  - [Must the accident victim be protected from the emergency physician?].

PMID- 9577212
TI  - [Must the accident victim be protected from the emergency physician?].
AB  - Quality control in preclinical medical care has become a matter of concern in
      recent years. In order to evaluate the quality of treatment one has to set
      standards. Most of the current standards were defined by different preclinical
      care organisations and are also accepted in the unique emergency medical care
      protocol used in the Federal Republic of Germany. Considering these standards, we
      retrospectively analyzed the preclinical treatment of all multiple trauma
      patients admitted to our department between 1985 and 1996. The major issues of
      this analysis were the diagnoses, the indications for invasive measures and the
      performance. Regarding the triage, for example, it was noted that 28% of patients
      who should have been admitted to a level I trauma center considering the severity
      of their injury were first admitted to a level III hospital and needed to be
      transferred later. In 7% of patients two additional mistakes and in 4% of
      patients more than two mistakes in the triage were noted. On the other hand,
      there are records of patients who were considered to be only slightly injured but
      received invasive treatment. Preclinical intubation and mechanical ventilation
      was not performed in 16.5% although the severity of injury clearly demanded it. A
      thoracic drain tube was not positioned in 38% of patients suffering from severe
      thoracic trauma (AISThorax > or = 4). Insufficient application of resuscitation
      volume (< 2500 ml on admission) was evident in 17% of all documented patients.
      According to our results, the initial evaluation of severity of injury is still a
      major problem and leads to wrong decisions for treatment. Although the
      qualification of ambulance physicians has been standardized for some years, there
      are still clear deficits in the preclinical management of trauma patients that
      need to be targeted.

PMID- 9577213
TI  - [Lifting osteotomy of the acromion as a new principle in treatment of impingement
      syndrome, especially in correlation with reconstruction of large rotator cuff
      lesions].
AB  - There are many different causes leading to impingement lesions of the shoulder
      (e.g., architecture of the acromion, arthritis of the acromioclavicular joint,
      bursitis subacromialis, chronic instability). There are also different ways of
      treating it. Neer described his technique of anterior acromioplasty in 1972. With
      this technique there is sometimes a limitation in the amount of resection
      possible because of the anatomical findings (i.e., very curved or small
      acromion). We developed a new technique: the lift-up osteotomy of the acromion
      (LOA). This technique allows us to gain as much subacromial space as needed
      (e.g., for large anterior deltoid flaps). Osteotomy of the acromion gives an
      excellent view of the rotator cuff. Even large lesions can easily be repaired.
      After the cuff repair is done, the acromion is refixed with two canulated screws.
      So far, we have used this LOA technique in more than 100 patients in impingement
      operations, cuff repairs and anterior deltoid flaps all with good results.

PMID- 9577214
TI  - [Considerations on the management of subtotal and total macro-amputation of the
      upper extremity].
AB  - Between 1982 and 1993, 65 amputation and amputation-like injuries in the upper
      arm (n = 18), proximal and middle forearm (n = 32) and distal forearm and wrist
      level (n = 15) were treated in our institution. The overall survival rate in our
      series was 92.3% (60/65). In 3 of 65 cases early secondary amputation because of
      vascular failure was necessary. There was one reamputation because of deep
      infection with beginning sepsis. Severe systemic disturbances were seen in one
      patients, requiring early reamputation. Twenty-five patients with a follow-up of
      more than 2 years were reviewed in a retrospective clinical study and evaluated
      according to the Chen classification. Of 8 patients with upper-arm involvement, 2
      had a grade II result, 4 a grade III and 2 a grade IV result. There were 1 grade
      I, 2 grade II, 2 grade III and 5 grade IV results in the proximal forearm group.
      In the distal forearm group 2 patients each showed a grade I, II and III result
      and 1 a grade IV. Taking grades I and II results together, a "functional
      extremity" could be reconstructed at the upper arm level in 25%, proximal forearm
      30%, and the distal forearm in 58%. The main advantage of
      replantation/revascularization of the upper limb is the possibility of restoring
      some sensitivity to the hand in addition to partial motor recovery, which always
      provides twice as much individual motor function as is offered by any type of
      prosthesis currently available. The higher cost and number of operations needed,
      as well as the longer postoperative care and longer disability time after
      replantation/revascularization are nevertheless justified by the significant
      increase in quality of life.

PMID- 9577215
TI  - [Elbow para-articular pseudarthrosis. Etiology and treatment].
AB  - Non-unions in the proximity of the elbow are very rare and in most cases caused
      by mistakes in initial treatment. Reconstruction after pseudarthrosis of the
      elbow continues to pose a challenge for any surgeon. The aim of our study was to
      analyze the initial mistakes and to underline the most important aspects of
      reconstructive surgery. In a retrospective study over a defined period of 10
      years (1/1985 to 12/1994) we were able to treat altogether 27 non-unions in the
      proximity of the elbow. These patients were transferred to our hospital at an
      average of 44 weeks after initial therapy elsewhere. The main symptoms were in 17
      cases pain and in all other patients functional deficit. Reconstructive surgery
      was performed an average 54 weeks after the primary injury. In 24 out of 27 cases
      a re-osteosynthesis, in 12 an arthrolysis, in 7 a neurolysis and in 2 cases an
      arthroplasty was needed. The patient could return to work an average 18 weeks
      after the operation and 53 weeks after injury. The initial complaints were
      reduced in 24 of 27 cases, with a significant improvement in the ROM and
      functional outcome according to the Mayo Elbow Performance Index.

PMID- 9577216
TI  - [A new device for positioning cerclage of the acetabulum].
AB  - Open reduction with internal stabilization is considered to be the standard
      therapy for the treatment of displaced acetabular fractures. The internal
      fixation is routinely achieved by the use of plates and screws. The use of
      cerclage wires and cables as a reduction aid and definitive implant for
      stabilization has only occasionally been reported in the literature. The
      indication was mostly limited to use in elderly patients with insufficient bone
      stock. A newly instrument developed on the basis of a standard bone elevator is
      presented. It allows a safe, semiclosed application of a cerclage wire around the
      greater ischiatic notch through use of the second window of the ilioinguinal
      approach. A wide dissection at the "outside" of the pelvis is not necessary.

PMID- 9577217
TI  - [Resilience of tibial transplant fixation for replacement of the anterior
      cruciate ligament. Interference screws vs. staples].
AB  - The endoscopic single incision technique for ACL reconstruction with a femoral
      half-tunnel may lead to a graft/tunnel mismatch and subsequent protrusion of the
      block from the tibial tunnel. The typical tibial fixation with an interference
      screw is not possible in these cases. Fixation with staples in a bony groove
      inferior to the tunnel outlet can be used as an alternative technique. Current
      literature does not provide biomechanical data of both fixation techniques in a
      human model. This study was performed to evaluate primary biomechanical
      parameters of this technique compared to a standard interference screw fixation
      of the block. 55 fresh-frozen human cadaver knee joints of a younger age (mean
      age: 44 years) were used. Grafts were harvested from the patellar tendon
      midportion with bone blocks of 25 mm length and 9 mm width. A 10 mm tibial tunnel
      was drilled from the anteromedial cortex to the center of the tibial insertion of
      the ACL. 3 different sizes of interference screws (7 x 30, 9 x 20 and 9 x 30 mm)
      were chosen as a standard control procedure (n = 40). For tibial bone-block
      fixation the graft was placed through the tunnel, the screw was then inserted on
      the cancellous or the cortical surface respectively. 15 knees were used for
      staple fixation. A groove was created inferior to the tunnel outlet with a
      chisel. The bone block was fixed in this groove with 2 barbed stainless steel
      staples. Tensile testing in both of the groups was carried out under axial load
      parallel to the tibial tunnel in a Zwick-testing-machine with a velocity of 1
      mm/sec. Dislocation of the graft and stiffness were calculated at 175 N load.
      Maximum load to failure using interference screws varied between 506 and 758 N.
      Load to failure using staples was 588 N. Dislocation of the graft ranged between
      3.6 and 4.7 mm for interference screw fixation and was 4.2 mm for staples. With
      both fixation techniques, the recorded failure loads were sufficient to withstand
      the graft loads which are to be expected during the rehabilitation period. Staple
      fixation of the bone block outside of the tunnel resulted in fixation strength
      comparable to interference screw fixation.

PMID- 9577218
TI  - [Diagnosis of anterior knee instability. Comparison between the Lachman test, the
      KT-1,000 arthrometer and the ultrasound Lachman test].
AB  - We reviewed 45 patients on average 14.7 years after surgery for rupture of the
      anterior cruciate ligament. The aim of the study was to compare the reliability
      of the Lachman test to evaluation of knee laxity with the KT 1000 arthrometer and
      the ultrasound-assisted Lachman test. Forty-five knees were examined with the
      Lachman test: 12 knees showed no sign of instability; 20 had a + positive Lachman
      test with a hard end point; 6 with a + positive test had no end point and were
      rated as unstable; a +2 Lachman test was found in 7 knees. With the KT 1000
      Arthrometer 44 knees were examined: 30 knees were graded as stable according to
      the criteria of Daniel; 14 knees were unstable. We used the ultrasound-guided
      Lachman test in 44 knees. Taking only the side-to-side difference into account,
      37 knees were stable and 7 unstable. According to Gruber, a single translation
      greater than 4 mm is also a sign of instability. Therefore, 12 knees were
      unstable, although 6 of these knees were rated as stable, taking the side-to-side
      difference into account. Comparing the two instrument measurements, all knees
      with ultrasound-rated instability on the basis of side-to-side measurements were
      also rated as unstable with the KT 1000 arthrometer. Only half of the knees rated
      as unstable because of a single translation greater than 4 mm with the ultrasound
      technique were rated as unstable with the KT 1000 arthrometer. Our results show
      that the accuracy of the Lachman test is as good as the instrument evaluation if
      the end point is taken into consideration. A positive Lachman test indicating
      anterior knee laxity is one where the soft end point is as described by Torg et
      al. Both instrument measurements are accurate in indicating anterior knee laxity,
      but only if they are used by an experienced examiner. Using the side-to-side
      measurements, the sensitivity of the KT 1000 arthrometer is higher. If only
      single translations greater than 4 mm without a significant side-to-side
      difference with the ultrasound technique are interpreted as anterior knee
      instability, then some knees will be rated as unstable, although both the
      clinical and KT 1000 arthrometer examinations prove them to be stable. We believe
      that only a side-to-side difference with the instrument techniques should be
      interpreted as knee laxity. Borderline positive measurements should only be used
      together with the clinical findings. Both instrument measurements can help to
      improve the quality of the clinical examination if the examiners are
      inexperienced. If instrument measurements are required, we believe that the
      ultrasound technique is easy and cheap to perform. Nevertheless, we believe that
      instrument measurements of anterior knee laxity are not necessary if a thorough
      clinical examination is performed, taking the end point of the Lachman test into
      consideration.

PMID- 9577219
TI  - [Dislocated cuboid fracture. Clinical aspects and therapy of a rare foot injury].
AB  - Fractures of the cuboid are very rare. During the last 10 years four patients
      with isolated fractures of the cuboid have been treated in our hospital. The
      displaced fractures were treated by open reduction, bone grafting where
      necessary, and internal fixation. At the time of follow-up the results concerning
      pain and function were good to excellent and better than those previously
      reported for conservative treatment. We recommend this treatment for fractures
      with displacement of one or more of the articular surfaces or with shortening of
      the lateral arch of the foot.

PMID- 9577220
TI  - [The unstable shoulder. Classification and therapy].

PMID- 9577221
TI  - [Acute compartment syndrome of the lower leg after ankle joint sprain. A case
      report].
AB  - In the field of traumatology, compartment syndromes of the lower extremity are
      often seen after fractures and direct injuries, or after ischaemia. Other causes
      include over-exertion and non-traumatic causes such as acute rhabdomyolysis, drug
      induced myositis and eosinophilic myositis. This paper describes the clinical and
      MR course of a compartment syndrome following an ankle sprain.

PMID- 9577222
TI  - [Removal of a massive broken tibial intramedullary nail].
AB  - A problem arose when the reamed tibia nail was replaced by a massive unreamed
      tibia nail. Of the nail fractures, it is difficult to remove the distal fragment
      from the medullary cavity. It may also happen that the connecting screw between
      the insertion handle and the nail breaks off at the edge of the implant, which
      complicates removal of the nail. The authors have developed a technique for
      removing the implant without having to saw a fissure in the marrow. A concave
      instrument is slid over the part of the nail left behind after which the two are
      connected by means of a K wire. This method has been successfully applied in two
      patients.

PMID- 9577223
TI  - [Dorsal removal and stabilization of giant cell tumor of the thoracic spine].
AB  - The incidence of giant cell tumors accounts for less than 5% of all bone tumors.
      In the thoracic spine these tumors are extremely rare (1-1.5% of the giant-cell
      tumors). The potential malignant character of giant cell tumors of the spine
      usually leads to wide surgical extirpation by ventral approach. The filling of
      bone defects with palacos cement after tumor resection is sufficient in the
      metaphysis of long bones. The case presented here is a giant cell tumor of the
      upper thoracic spine with primarily posterior destruction of the vertebral body
      and left arch. A single dorsal approach allowed for intralesional resection and
      filling of the defect with bone cement. This procedure was sufficient to achieve
      a solid fixation without recurrence of the giant cell tumor.

PMID- 9577224
TI  - Environmental health services in Europe. 2. Policy options.

PMID- 9577226
TI  - [Choking under pressure: Positive public expectations and performance in a motor
      task].
AB  - According to Baumeister (e.g. 1985) "choking under pressure" means showing a
      suboptimal performance when under pressure, despite a high motivation to perform
      well. Factors that can exert pressure on performers ("pressure variables")
      include competition, the reward to be gained, the expectation of negative
      consequences, the presence of spectators etc. However, "choking" can also occur
      when public expectations (e.g., of the audience) are positive. Baumeister et al.
      (1985) showed this in two experiments. In the present study an experimental
      design (a 2 x 2 design) was developed to examine this question in a sport
      context. Under various conditions of public expectations ("positive" vs "no") and
      private expectations ("positive" vs "negative"), 60 university students
      repeatedly had to do a motor task on a rowing ergometer. The main results were:
      When the public expects success, but not the performing person, then the level of
      performance decreases. Under the condition of "public expectation of success" a
      better performance was only shown when the private and the public expectations
      corresponded with each other.

PMID- 9577225
TI  - [Pain patients show a higher hindsight bias].
AB  - Research on pain-related cognitions has up to now predominantly relied upon
      introspective questionnaire data. Experimental cognitive psychology offers an
      alternative way of access to the cognitive aspects of chronical pain. Building on
      the assumption that information-processing is in part uncontrolled, automatic and
      pre-attentive, similar processes are also expected to be relevant for pain
      relevant cognitions and to be involved in health-related convictions and in
      coping strategies that can be assessed with questionnaires. Cognitive
      psychological research has established the "hindsight bias" as a robust
      phenomenon that occurs uncontrolled and automatically in diverse contexts when a
      prior judgment or prediction is assimilated to information received later on. The
      hindsight bias may be regarded as a manifestation of a universal cognitive
      mechanism, meaning that information (including information about emotional
      states) available at a given time will change the memory of prior judgments or of
      predictions of future events and results of behavior. Cognitive biases similar to
      the hindsight effect have been demonstrated in chronical pain patients. The
      present work elaborates the hypothesis that pain patients differ from other
      groups in the size of the hindsight bias and in its composition and outlines how
      it can contribute to the chronification of pain. Data from a hindsight-bias
      experiment comparing pain patients, psychiatric patients and students are
      analyzed using alternatively a traditional global hindsight bias score ("Hell
      Index") and a multinomial modelling approach. The hindsight-effect was observed
      in the usual extent in the student control group, but was significantly greater
      in the pain group and absent in the psychiatric sample. In addition to this
      global finding, multinomial modelling revealed group differences in specific
      model parameters. This method of analysis thus proved as promising for the
      assessment of cognitive aspects of clinical disorders.

PMID- 9577227
TI  - Environmental dehalogenation: chemistry and mechanism.
AB  - The halogen cycle is one of the great chemical cycles on earth. Haloorganics are
      both synthesized and destroyed by the chemistry that controls their flux and
      form. The synthetic leg of the cycle is both biotic and abiotic in nature. The
      biotic synthesis results primarily from the biochemical activity of marine algae
      and kelp, although these are by no means the only sources. The abiotic process is
      vested in large part in volcanic eruption and emission of gases synthesized as a
      thermal consequence of venting the earth's core.

PMID- 9577228
TI  - Reconstructing the protein-water interface.
AB  - Using molecular dynamics simulations of fully hydrated proteins and analysis of
      crystal structures contained in the Protein Data Bank, we develop a transferable
      set of perpendicular radial distribution functions for water molecules around
      globular proteins. These universal functions may be used to reconstruct the
      unique three-dimensional solvent density distribution around every individual
      protein with a modest error. We discuss potential applications of this solvent
      treatment in protein x-ray crystallographic refinements and in theoretical
      modeling. We also present a fast, grid-based algorithm for construction of the
      perpendicular solvent density distributions.

PMID- 9577229
TI  - Conformational behavior of the HAV-VP3(110-121) peptidic sequence and synthetic
      analogs in membrane environments studied by CD and computational methods.
AB  - The present study was undertaken to examine the structural features that may be
      important to explain the immunogenicity of the (110-121) peptide sequence
      (FWRGDLVFDFQV) of VP3 capsid protein of hepatitis A virus. A conformational
      analysis of the preferred conformations by CD and molecular mechanics was carried
      out. Present results suggest that the interaction with liposomes as biomembrane
      model induces and stabilizes the amphipathic beta-structure of the peptide. To
      study the contribution of amino acid replacements at the RGD tripeptide as well
      as the influence of the peptide chain length on peptide conformation, solid-phase
      peptide synthesis of several peptide analogs was carried out and the peptide
      conformation was studied using CD spectroscopy. The results show that the RGD
      sequence is necessary to induce the beta-structure in the presence of liposomes.

PMID- 9577230
TI  - Resolution of Trp near UV CD spectra of calmodulin-domain peptide complexes into
      the 1La and 1Lb component spectra.
AB  - Near uv CD spectra of Trp residues in proteins frequently show a complex line
      shape deriving from the overlap of 1La and 1Lb electronic transitions. This study
      presents an original empirical method of resolving these components, based on the
      near uv CD spectra of well-defined complexes of calmodulin domains with target
      peptides containing a single Trp residue and derived from the skeletal muscle
      myosin light chain kinase target sequence. Spectra of 4 complexes were used to
      obtain the 1La and 1Lb component spectra that were then used to analyze further
      complexes. The broad and featureless 1La spectrum is centered at 279 nm, the 1Lb
      spectrum shows vibrational fine structure with maxima at 274.9, 281.5, and 289.8
      nm. The CD spectrum of most complexes could successfully be fitted with one 1La
      and one 1Lb spectrum, the 1Lb spectrum being negative for all complexes but the
      1La spectrum showing either positive or negative sign. Spectra of some complexes,
      however, failed to be adequately represented by only one 1La and one 1Lb
      spectrum. Instead, they could be fitted with one 1Lb spectrum and two 1La spectra
      with different sign and position. The method is successful in identifying and
      quantitating the relative intensities of a two-component system, consistent with
      a single conformation for tryptophan in a protein, and provides a simple
      indication of cases where a more complicated explanation is required.

PMID- 9577232
TI  - Linking service climate and customer perceptions of service quality: test of a
      causal model.
AB  - A set of foundation issues that support employee work and service quality is
      conceptualized as a necessary but not sufficient cause of a climate for service,
      which in turn is proposed to be reflected in customer experiences. Climate for
      service rests on the foundation issues, but in addition it requires policies and
      practices that focus attention directly on service quality. Data were collected
      at multiple points in time from employees and customers of 134 branches of a bank
      and analyzed via structural equation modeling. Results indicated that the model
      in which the foundation issues yielded a climate for service, and climate for
      service in turn led to customer perceptions of service quality, fit the data
      well. However, subsequent cross-lagged analyses revealed the presence of a
      reciprocal effect for climate and customer perceptions. Implications of these
      results for theory and research are offered.

PMID- 9577231
TI  - Effect of temperature on DNA secondary structure in the absence and presence of
      0.5 M tetramethylammonium chloride.
AB  - Changes in the average secondary structures of three different linear DNAs over
      the premelting region from 5 to 60 degrees C were investigated by measuring their
      CD spectra and also their torsion elastic constants (<alpha>) by time-resolved
      fluorescence polarization anisotropy. For one of these DNAs, the Haell fragment
      of pBR322, the apparent diffusion coefficients [Dapp(k)] at small and large
      scattering vectors (k) were also measured by dynamic light scattering. With
      increasing temperature, all three DNAs exhibited typical premelting changes in
      their CD spectra, and these were accompanied by 1.4- to 1.7-fold decreases in
      <alpha>. Also for the 1876 base pair fragment, Dapp(k) at large scattering
      vectors, which is sensitive to the dynamic bending rigidity, decreased by 17%,
      even though there was no change at small scattering vectors, where Dapp(k) = D0
      is the translational diffusion coefficient of the center-of-mass. These
      observations demonstrate conclusively that the premelting CD changes of these
      DNAs are associated with a significant change in average secondary structure and
      mechanical properties, though not in persistence length. In the presence of 0.5 M
      tetramethylammonium chloride (TMA-Cl) the premelting change in CD is largely
      suppressed, and the corresponding changes in <alpha> and Dapp(k) at large
      scattering vectors are substantially diminished. These observations suggest that
      TMA-Cl, which binds preferentially to A.T-rich regions and stabilizes those
      regions (relative to G.C-rich regions) against melting, effectively stabilizes
      the prevailing low-temperature secondary structure sufficiently that the DNA is
      effectively trapped in that state over the temperature range observed.

PMID- 9577233
TI  - Type of affirmative action policy: a determinant of reactions to sex-based
      preferential selection?
AB  - In 3 studies, 150 undergraduates and 75 MBA students, men and women, were exposed
      to selection policies differing in the degree to which merit and group membership
      were weighted in selection decisions involving women. Results indicated that in
      self-views and self-assessments of beneficiaries (Study 1), competence
      perceptions on the part of others (Study 2), and work-related reactions of
      nonbeneficiaries (Study 3), many, but not all, negative reactions to sex-based
      preferential selection were alleviated when the policy made clear that merit
      considerations were central to the decision-making process. In the absence of
      information about policy type, participants acted as if merit had not been a
      factor in preferential selection decisions.

PMID- 9577234
TI  - The effects of organizational citizenship behavior on performance judgments: a
      field study and a laboratory experiment.
AB  - The process linking organizational citizenship behavior (OCB) with performance
      judgments was investigated in a field and a laboratory study. In the field study,
      managers rated the task performance and OCB of 148 subordinates. In the
      laboratory research, 136 students viewed and rated videotaped segments of
      teaching performance that demonstrated either high or low task performance and
      high or low OCB. In both studies, liking and perceived affective commitment
      mediated the relationship between OCB and overall evaluation. Liking also
      mediated the relationship between OCB and reward recommendations. Further, the
      field study indicated that the causal motive attributed by the manager for the
      employee's OCB mediated the relationship between OCB and overall evaluation.

PMID- 9577235
TI  - Job characteristics, work-school conflict, and school outcomes among adolescents:
      testing a structural model.
AB  - A conceptual model of work-school conflict was developed and tested. This study
      extends prior adolescent employment research by investigating the process by
      which job characteristics are associated with school outcomes. Data were obtained
      from a sample of 319 adolescents (16 to 19 years old) who were full-time students
      and part-time workers. The model was tested using structural equation modeling
      techniques. Results supported the hypothesized path model. Job characteristics
      (workload, number of work hours, and job dissatisfaction) were positively related
      to work-school conflict. Work-school conflict was negatively related to school
      readiness. School readiness was positively related to school performance, which
      was negatively associated with school dissatisfaction. In addition, results
      support a feedback relation, such that school dissatisfaction is negatively
      related to school readiness.

PMID- 9577236
TI  - Perceived organizational support and police performance: the moderating influence
      of socioemotional needs.
AB  - Police patrol officers were surveyed to investigate how the strength of
      socioemotional needs affects the relationship between perceived organizational
      support (POS) and work performance. The association of POS with driving-under-the
      influence arrests and speeding citations generally increased with strength of the
      needs for esteem, affiliation, emotional support, and social approval. Patrol
      officers with strong socioemotional needs, but not those with weak needs, showed
      a positive relationship between POS and performance. The findings are consistent
      with social exchange views that maintain (a) work effort is encouraged by the
      receipt of socioemotional resources, (b) POS fulfills a variety of socioemotional
      needs, and (c) the value of POS and the obligation to reciprocate with high
      performance increase with the strength of socioemotional needs.

PMID- 9577237
TI  - Selective attention: a reevaluation of the implications of negative priming.
AB  - The notion that inhibitory processes play a critical role in selective attention
      has gained wide support. Much of this support derives from studies of negative
      priming. The authors note that the attribution of negative priming to an
      inhibitory mechanism of attention draws its support from a common assumption
      underlying priming procedures, together with the procedure that has been used to
      measure negative priming. The results from a series of experiments demonstrate
      that selection between 2 competing prime items is not required to observe
      negative priming. This result is demonstrated across several experiments in which
      participants named 1 of 2 items in a second display following presentation of a
      single-item prime. The implications of these results for existing theories of
      negative priming are discussed, and a theoretical framework for interpreting
      negative priming and several related phenomena is forwarded.

PMID- 9577238
TI  - Traits and motives: toward an integration of two traditions in personality
      research.
AB  - After reviewing classic and current conceptions of trait (as measured by
      questionnaires) and motive (as measured by the Thematic Apperception Test [TAT]
      or other imaginative verbal behavior), the authors suggest that these 2 concepts
      reflect 2 fundamentally different elements of personality--conceptually distinct
      and empirically unrelated. The authors propose that traits and motives interact
      in the prediction of behavior: Traits channel the behavioral expression of
      motives throughout the life course. The authors illustrate this interactive
      hypothesis in 2 longitudinal studies, focusing on the broad trait of extraversion
      and the 2 social motives of affiliation and power. In interaction with
      extraversion, both motives show predicted and replicated relations to
      independently measured life outcomes in the domains of relationships and careers.
      Extraversion facilitates unconflicted motive expression, whereas introversion
      deflects social motives away from their characteristic goals and creates
      difficulties in goal attainment.

PMID- 9577239
TI  - Echoes of echoes? An episodic theory of lexical access.
AB  - In this article the author proposes an episodic theory of spoken word
      representation, perception, and production. By most theories, idiosyncratic
      aspects of speech (voice details, ambient noise, etc.) are considered noise and
      are filtered in perception. However, episodic theories suggest that perceptual
      details are stored in memory and are integral to later perception. In this
      research the author tested an episodic model (MINERVA 2; D. L. Hintzman, 1986)
      against speech production data from a word-shadowing task. The model predicted
      the shadowing-response-time patterns, and it correctly predicted a tendency for
      shadowers to spontaneously imitate the acoustic patterns of words and nonwords.
      It also correctly predicted imitation strength as a function of "abstract"
      stimulus properties, such as word frequency. Taken together, the data and theory
      suggest that detailed episodes constitute the basic substrate of the mental
      lexicon.

PMID- 9577240
TI  - Interpreting the influence of implicitly activated memories on recall and
      recognition.
AB  - A model concerning the influence of implicitly activated information on cued
      recall and recognition is presented. The model assumes that studying a familiar
      word activates its associates and creates an implicit representation in long-term
      working memory. Test cues also activate their associates, with memory performance
      determined by a sampling process that operates on the intersection of information
      activated by the test cue with information previously activated by the studied
      word. Successful sampling is enhanced by preexisting connections among the
      associates of the studied word and by preexisting connections between it and the
      retrieval cue. However, the usefulness of the implicit representation is reduced
      by the activation of competing associates and by shifts of attention before
      testing. Experiments designed to test predictions of the model indicate that the
      associates of a familiar word can exert a powerful effect on its cued recall and
      recognition.

PMID- 9577241
TI  - From normal fear to pathological anxiety.
AB  - In this article the authors address how pathological anxiety may develop from
      adaptive fear states. Fear responses (e.g., freezing, startle, heart rate and
      blood pressure changes, and increased vigilance) are functionally adaptive
      behavioral and perceptual responses elicited during danger to facilitate
      appropriate defensive responses that can reduce danger or injury (e.g., escape
      and avoidance). Fear is a central motive state of action tendencies subserved by
      fear circuits, with the amygdala playing a central role. Pathological anxiety is
      conceptualized as an exaggerated fear state in which hyperexcitability of fear
      circuits that include the amygdala and extended amygdala (i.e., bed nucleus of
      the stria terminalis) is expressed as hypervigilance and increased behavioral
      responsivity to fearful stimuli. Reduced thresholds for activation and
      hyperexcitability in fear circuits develop through sensitization- or kindling
      like processes that involve neuropeptides, hormones, and other proteins.
      Hyperexcitability in fear circuits is expressed as pathological anxiety that is
      manifested in the various anxiety disorders.

PMID- 9577242
TI  - Modeling memory for absolute location.
AB  - A model for recall of location is presented that postulates 2 encoding processes:
      1 producing exact (all-or-none) recall, the other resulting in inexact recall.
      Exact recall is modeled as the outcome of a perceptual discrimination process,
      and inexact recall is modeled as the incomplete outcome of a Poisson process of
      information gain. The model accurately predicts levels of recall and patterns of
      errors in a number of experiments and articulates a lawful relationship between
      recall and elements of picture composition, such as the dimensions of the to-be
      recalled attributes and the configuration of anchor points in the picture. This
      model enables a reappraisal of previous theoretical approaches to memory for
      location and of related studies concerned with automaticity in memory. The
      significance of this model as a general analytical device for the study of
      continuous attributes in memory is discussed.

PMID- 9577243
TI  - A critique of Bem's "Exotic Becomes Erotic" theory of sexual orientation.
AB  - Two critiques of D. J. Bem's (1996) "Exotic Becomes Erotic" (EBE) theory of
      sexual orientation are presented. First, the core proposition of EBE theory is
      considered; that is, the idea that adults are erotically attracted to the gender
      based class of peers (males or females) who were dissimilar or unfamiliar to them
      in childhood. Studies cited by Bem and additional research show that EBE theory
      is not supported by scientific evidence. Second, Bem's claim that his theory
      applies equally to both sexes is questioned; instead the argument that it
      neglects and misrepresents women's experiences is made. Bem's conceptualization
      of erotic desire and his analysis of gender nonconformity illustrate this
      problem. It is suggested that different theories may be needed to explain the
      development of men's and women's sexual orientation.

PMID- 9577244
TI  - Is EBE theory supported by the evidence? Is it androcentric? A reply to Peplau et
      al. (1998)
AB  - In their critique of the author's Exotic-Becomes-Erotic (EBE) theory of sexual
      orientation (D. J. Bem, 1996), L. A. Peplau, L. D. Garnets, L. R. Spalding, T. D.
      Conley, and R. C. Veniegas (1998) challenge his reading of the evidence
      concerning the antecedents of sexual orientation; they also contend that the
      theory neglects women's experiences. In reply, the author argues that L. A.
      Peplau et al. have misunderstood the critical antecedent variable of the theory
      and, hence, have misidentified the particular empirical findings that would serve
      to confirm or disconfirm its central contentions. The author also argues that the
      sex differences they cite are not relevant to the theory, whereas an important
      sex difference they do not cite is actually anticipated by it.

PMID- 9577245
TI  - The role of hidden food allergy/intolerance in chronic disease.
AB  - A large body of medical literature has indicated that hidden food allergy is a
      frequent cause of a wide range of physical and mental conditions. Hidden
      allergies can be "unmasked" by means of an elimination diet, followed by
      individual food challenges. Although the concept of hidden food allergy remains
      controversial, the evidence strongly suggests that identification and avoidance
      of allergenic foods can relieve a number of common and difficult-to-treat medical
      problems.

PMID- 9577246
TI  - Estriol: safety and efficacy.
AB  - While conventional hormone replacement therapy provides certain benefits, it is
      not without significant risks. Estriol has been found to provide some of the
      protection without the risks associated with stronger estrogens. Depending upon
      the situation, estriol may exert either agonistic or antagonistic effects on
      estrogen. Estriol appears to be effective at controlling symptoms of menopause,
      including hot flashes, insomnia, vaginal dryness, and frequent urinary tract
      infections. Results of research on its bone-density-maintaining effects have been
      contradictory, with the most promising results coming from Japanese studies.
      Estriol's effect on cardiac risk factors has also been somewhat equivocal;
      however, unlike conventional estrogen prescriptions, it does not seem to
      contribute to hypertension. Although estriol appears to be much safer than
      estrone or estradiol, its continuous use in high doses may have a stimulatory
      effect on both breast and endometrial tissue.

PMID- 9577247
TI  - Clinical applications of N-acetylcysteine.
AB  - N-acetylcysteine (NAC), the acetylated variant of the amino acid L-cysteine, is
      an excellent source of sulfhydryl (SH) groups, and is converted in the body into
      metabolites capable of stimulating glutathione (GSH) synthesis, promoting
      detoxification, and acting directly as free radical scavengers. Administration of
      NAC has historically been as a mucolytic agent in a variety of respiratory
      illnesses; however, it appears to also have beneficial effects in conditions
      characterized by decreased GSH or oxidative stress, such as HIV infection,
      cancer, heart disease, and cigarette smoking. An 18-dose oral course of NAC is
      currently the mainstay of treatment for acetaminophen-induced hepatotoxicity. N
      acetylcysteine also appears to have some clinical usefulness as a chelating agent
      in the treatment of acute heavy metal poisoning, both as an agent capable of
      protecting the liver and kidney from damage and as an intervention to enhance
      elimination of the metals.

PMID- 9577248
TI  - Therapeutic applications of taurine.
AB  - Taurine is a conditionally-essential amino acid which is not utilized in protein
      synthesis, but rather is found free or in simple peptides. Taurine has been shown
      to be essential in certain aspects of mammalian development, and in vitro studies
      in various species have demonstrated that low levels of taurine are associated
      with various pathological lesions, including cardiomyopathy, retinal
      degeneration, and growth retardation, especially if deficiency occurs during
      development. Metabolic actions of taurine include: bile acid conjugation,
      detoxification, membrane stabilization, osmoregulation, and modulation of
      cellular calcium levels. Clinically, taurine has been used with varying degrees
      of success in the treatment of a wide variety of conditions, including:
      cardiovascular diseases, hypercholesterolemia, epilepsy and other seizure
      disorders, macular degeneration, Alzheimer's disease, hepatic disorders,
      alcoholism, and cystic fibrosis.

PMID- 9577249
TI  - Allergenic foods and their substitutes.

PMID- 9577250
TI  - Crataegus oxycantha. Common name: hawthorne.

PMID- 9577251
TI  - Quercetin.

PMID- 9577253
TI  - Keep on walking, keep on living.

PMID- 9577252
TI  - Emotions and health. Can stress make you sick?

PMID- 9577254
TI  - Drug prevents bone loss in healthy women.

PMID- 9577255
TI  - I keep seeing ads for fiber supplements that are supposed to lower cholesterol.
      Are they worth taking?

PMID- 9577256
TI  - Brain tumor. Better treatments for an enigmatic disease.

PMID- 9577257
TI  - Safer arthritis drugs on the horizon.

PMID- 9577258
TI  - B vitamins may cut heart disease risk.

PMID- 9577259
TI  - Alcohol and breast cancer.

PMID- 9577260
TI  - Vitamins, minerals, diet, and prostate cancer.

PMID- 9577261
TI  - Exercise and blood pressure.

PMID- 9577262
TI  - Caloric restriction and longevity.

PMID- 9577263
TI  - Treating prostate cancer: another step forward.

PMID- 9577265
TI  - I know that gallbladders can be removed through tiny incisions using new types of
      instruments. Can the prostate also be removed this way?

PMID- 9577264
TI  - I'm a 57-year-old man with high blood pressure and high cholesterol. I had a hard
      time regulating my pressure until I went on Vasotec, which was great. But I
      developed a cough, so my doctor switched me to Cozaar. My cough stopped and my
      pressure seems okay, but I'd like to know what you think of the switch.

PMID- 9577266
TI  - Some tests you may not need.

PMID- 9577267
TI  - Treating fibroids.

PMID- 9577268
TI  - Food as medicine.

PMID- 9577269
TI  - How estrogen works.

PMID- 9577270
TI  - Alzheimer's and antiinflammatories.

PMID- 9577271
TI  - Exercise: a few walks will do you.

PMID- 9577272
TI  - I have recently taken up fast walking and have developed pain in my left foot,
      which my internist says in plantar fasciitis. She told me to hold off on walking
      for a while. Can you tell me about this condition? Is there anything else I can
      do to speed my recovery?

PMID- 9577273
TI  - In 1992 I had a hysterectomy. I was 46 years old at the time. My gynecologist
      prescribed Premarin 1.25 mg and would like me to continue this dose. Recently, my
      internist recommended that I take 0.625 mg per day. Who is right?

PMID- 9577274
TI  - Hyponatraemia in the newborn.

PMID- 9577275
TI  - Treatment of hypoxic-ischaemic brain damage by moderate hypothermia.

PMID- 9577276
TI  - Hypothermic neural rescue treatment: from laboratory to cotside?

PMID- 9577277
TI  - Diagnostic tests for bacterial infection from birth to 90 days--a systematic
      review.
AB  - AIM: To determine the clinical value of common diagnostic tests for bacterial
      infection in early life. METHODS: A Medline search (1966-95) was undertaken to
      identify studies that reported the assessment of a diagnostic "test," predicting
      the presence or absence of bacterial infection in infants up to 90 days of age.
      The quality of each selected study was assessed using defined criteria. Data were
      extracted twice to minimise errors. RESULTS: Six hundred and seventy articles
      were identified. Two independent investigators agreed that 194 studies met the
      inclusion criteria (kappa = 0.85), 52 of which met primary quality criteria; 23
      studies reported data on (a) haematological indices, (b) C reactive protein
      evaluation, and (c) surface swab assessment. For haematological indices, the
      likelihood ratios for individual tests ranged from 20.4 (95% confidence interval
      7.3 to 56.8) for a white cell count < 7000/mm3 to 0.12 (0.04 to 0.37) for an
      immature:total (I:T) white cell ratio < 0.2. For C reactive protein evaluation,
      the likelihood ratios ranged from 12.56 (0.79 to 199.10) for a value of > 6 mg/l
      to 0.22 (0.08 to 0.65) for a negative value. For surface swab assessment, the
      likelihood ratios ranged from 33.6 (2.1 to 519.8) for a positive gastric aspirate
      culture to 0.08 (0.006 to 1.12) for microscopy of ear swab material that did not
      show any neutrophils. Likelihood ratios for combinations of these individual
      tests ranged from 10.17 (3.64 to 28.41) to 0.47 (0.22 to 1.00). CONCLUSIONS: The
      methodological quality of studies assessing the accuracy of diagnostic tests is
      generally poor. Even in rigorous studies, the reported accuracy of the tests
      varies enormously and they are of limited value in the diagnosis of infection in
      this population.

PMID- 9577278
TI  - Increased survival and deteriorating developmental outcome in 23 to 25 week old
      gestation infants, 1990-4 compared with 1984-9.
AB  - AIMS: To assess whether changes in survival over time in infants of 23 to 25
      weeks of gestational age were accompanied by changes in the incidence of
      disability in childhood during an 11 year period. METHODS: Obstetric and neonatal
      variables having the strongest association with both survival to discharge from a
      regional neonatal medical unit and neurodevelopmental disability in 192 infants
      of 23 to 25 weeks of gestation, born in 1984 to 1994, were studied as a group and
      in two cohorts (1984 to 1989 n = 96 and 1990 to 1994 n = 96). The data collected
      included CRIB (clinical risk index for babies) scores and cranial ultrasound scan
      findings. The children were followed up at outpatient clinics. RESULTS: Between
      1984 and 1989 (cohort 1) and 1990 and 1994 (cohort 2) the rate of survival to
      discharge increased significantly from 27% to 42% and the rate of disability in
      survivors increased from 38% to 68%; most of this increase was in mild
      disability. The proportions of survivors with cerebral palsy did not alter
      significantly (21% vs 18%), but more survivors with blindness due to retinopathy
      of prematurity (4% vs 18%), myopia (4% vs 15%) and squints (8% vs 13%)
      contributed to the increased rate of disability. Clinically significant cranial
      ultrasound findings and a high CRIB score were strongly associated with death. A
      high CRIB score was most strongly associated with disability. CONCLUSIONS: The
      rise in disability with improved survival was not due to cerebral palsy; rather
      the main contributors were blindness due to retinopathy, myopia, and squint. The
      causes of these disabilities seem to be linked to high CRIB scores. A system of
      regular and skilled retinal examination and access to facilities for retinal
      ablation should be in place in all neonatal units which undertake the care of
      such extremely preterm infants.

PMID- 9577279
TI  - Range of echocardiographic findings in term neonates with high oxygen
      requirements.
AB  - AIMS: To examine the hypothesis that right to left shunting occurs mainly in the
      lungs rather than through the fetal channels in neonates. METHODS: Thirty two
      term babies requiring over 70% oxygen had daily colour Doppler echocardiograms
      until recovery. Measurements included left ventricular fractional shortening,
      right and left ventricular outputs, colour and pulsed Doppler ductal and atrial
      shunting and systolic pulmonary artery pressure (SPAP) derived from ductal shunt
      or tricuspid incompetence velocities. RESULTS: The babies were retrospectively
      classified into a respiratory group (n = 19) and a persistent pulmonary
      hypertension (PPHN) group (n = 13) on the basis of clinical history and
      radiology. At the initial echocardiogram, just 50% of babies had suprasystemic
      SPAP. Despite better oxygenation, more of the PPHN group had suprasystemic PAP
      (85% vs 26%). A correlation between SPAP and Oxygen index (OI) was present only
      in the respiratory group (r = 0.7). Low ventricular outputs (< 150 ml/kg/min)
      were common in both groups (53% and 79%). The respiratory group had more closed
      ducts (47% vs 0%) and those ducts which were patient were more constricted (1.75
      mm vs 2.6 mm). Pure right to left ductal shunts were seen in just 15% and pure
      right to left atrial shunts in just 6% of all babies. The serial echocardiograms
      showed that SPAP fell and ducts closed well before oxygenation improved.
      Ventricular outputs increased with age in both groups. CONCLUSIONS: Apart from
      early on in the sickest babies with a primarily respiratory diagnosis and the
      babies with primary PPHN, most right to left shunting occurred at an
      intrapulmonary level.

PMID- 9577280
TI  - Outcome of resuscitation following unexpected apparent stillbirth.
AB  - There are few data to inform a decision to resuscitate babies who are
      unexpectedly stillborn. The outcome for 42 successfully resuscitated stillborn
      children, of whom 62% survived to be discharged home, is reported. Of the
      survivors, a poor outcome with severe disability was found in 23% (including one
      postneonatal death), equivocal outcome was found in 15% (two mild hypertonia; two
      with mild hemiplegia and no associated other disability) and 62% were free of any
      impairment at follow up 20 months to 8 years later. In 39 (93%) fetal problems
      had been identified and the resuscitation team was present at delivery. Poor
      outcome was associated with late return of heart beat, delayed respirations,
      neonatal acidaemia and early onset of seizures. Of the unexpected apparent
      stillbirths successfully resuscitated, 52% died or survived severely disabled,
      10% had an equivocal outcome, but 36% survived apparently intact. Therefore,
      vigorous resuscitation is clearly indicated in these circumstances.

PMID- 9577281
TI  - Modulation by magnesium of N-methyl-D-aspartate receptors in developing human
      brain.
AB  - AIM: To investigate age related alterations in glutamate N-methyl-D-aspartate
      (NMDA) receptor binding produced by the modulatory compounds glutamate, glycine,
      and magnesium (Mg2+) sulphate. METHODS: The effects produced by glutamate plus
      glycine, and Mg2+ on the binding of [3H]MK-801, a ligand for the N-methyl-D
      aspartate ion channel phencyclidine site, were measured in membrane preparations
      made from prefrontal cortex from human neonate (n = 5), infant (n = 6), and adult
      (n = 6) necropsy brains. RESULTS: Neonatal brains had the least [3H]MK-801
      binding, suggesting either a low density of NMDA receptors or a more restricted
      access of [3H]MK-801 to cation channel sites. Infant brains had the most [3H]MK
      801 binding which was stimulated to a greater extent by L-glutamate (100 microM)
      and glycine (10 microM) than in neonatal and adult brains. MG2+ invariably
      inhibited [3H]MK-801 binding. However, the Mg2+ IC50 value was higher in neonatal
      brain (3.6 mM) than infant (1.4 mM) and adult (0.87 mM) brains. CONCLUSION:
      Infant brain may have excess NMDA receptors which are hyper responsive to
      glutamate and glycine. The lower potency of Mg2+ to inhibit [3H]MK-801 binding in
      neonatal cortex may be because newborn babies have NMDA receptors without the
      normal complement of Mg2+ sites. The findings suggest that therapeutic NMDA
      receptor block in neonates requires higher concentrations of magnesium sulphate
      in brain tissue.

PMID- 9577282
TI  - Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly.
AB  - AIMS: To determine to what extent the Arg506 to Gln point mutation in the factor
      V gene and further genetic factors of thrombophilia affect the risk of
      porencephaly in neonates and infants. METHODS: The Arg506 to Gln mutation, factor
      V, protein C, protein S, antithrombin, antiphospholipid antibodies and
      lipoprotein (a) (Lp(a)) were retrospectively measured in neonates and children
      with porencephaly (n = 24). RESULTS: Genetic risk factors for thrombophilia were
      diagnosed in 16 of these 24 patients: heterozygous factor V Leiden (n = 3);
      protein C deficiency type I (n = 6); increased Lp (a) (n = 3); and protein S type
      I deficiency (n = 1). Three of the 16 infants had two genetic risk factors of
      thrombophilia: factor V Leiden mutation combined with increased familial Lp (a)
      was found in two, and factor V Leiden mutation with protein S deficiency type I
      in one. CONCLUSIONS: The findings indicate that deficiencies in the protein C
      anticoagulant pathway have an important role in the aetiology of congenital
      porencephaly.

PMID- 9577283
TI  - Complement and contact activation in term neonates after fetal acidosis.
AB  - AIMS: To evaluate complement and contact activation after fetal acidosis.
      METHODS: Fifteen term neonates with hypoxic-ischaemic encephalopathy after
      umbilical arterial pH < 7.10 were compared with 15 healthy neonates with
      umbilical arterial pH > 7.20. Determinations of the complement function and C1
      inhibitor activity were performed as kinetic tests 22-28 hours after birth. C1q,
      C1-inhibitor, and factor B concentrations were determined by radial
      immunodiffusion and those of C3a, C5a, and factor XIIa by enzyme immunoabsorbent
      assay. RESULTS: Median complement function (46 vs 73%), C1q (4.3 vs 9.1 mg/dl),
      and factor B (5.2 vs 7.7 mg/dl) decreased after fetal acidosis. The activated
      split products C3a (260 vs 185 micrograms/l), C5a (5.0 vs 0.6 micrograms/l), and
      factor XIIa (3.2 vs 1.3 micrograms/l) increased in the neonates after fetal
      acidosis. No differences were found in the concentration and activity of C1
      inhibitor. CONCLUSIONS: Complement and contact activation occurred in the
      newborns with hypoxic-ischaemic encephalopathy. Activation of these systems
      generates mediators which can trigger inflammation and tissue injury.

PMID- 9577284
TI  - Reduced expression of C5a receptors on neutrophils from cord blood.
AB  - AIM: To describe further functional deficiencies of neonatal neutrophils by
      measuring the expression of C5a receptors. METHODS: C5a uptake was measured using
      flow cytometry with fluorescein isothiocynate labelled recombinant C5a. The
      response of neutrophils to stimulation with C5a and fMLP was tested by measuring
      migration and exocytosis of myeloperoxidase and lactoferrin. RESULTS: C5a mean
      fluorescence on neutrophils from neonates was significantly lower (22.4 (SD 3.5))
      than in adult controls (31.5 (3.1)). Neutrophils from neonates migrated poorly
      towards both C5a and fMLP compared with those from adult controls. Exocytosis of
      myeloperoxidase, but not lactoferrin from neonatal neutrophils stimulated with
      C5a, was significantly lower than in adult controls. fMLP stimulation, on the
      other hand, resulted in significantly higher exocytosis in neonates. CONCLUSION:
      The lower expression of C5a receptors on neutrophils from neonates could be
      related to reduced C5a mediated exocytosis of myeloperoxidase.

PMID- 9577285
TI  - Cardiac effects of short course dexamethasone in preterm infants.
AB  - AIM: To examine the incidence and natural history of left ventricular hypertrophy
      (LVH) associated with the shorter 2-3 week course of dexamethasone, now more
      usual, for chronic lung disease. METHOD: Thirty one infants, gestational age 23
      34 (median 26) weeks, birthweight 500-2054 (median 815)g, received dexamethasone,
      starting at 0.4-0.6 mg/kg/day, at a median of 11 days of age (range 2-34),
      weaning over a period of 2-3 weeks. Eighteen preterm neonates were studied as
      controls over a similar time period. Serial echocardiographic measurements of end
      diastolic interventricular septum (IVSd) and left ventricular posterior wall
      (LVPWd) thicknesses were taken before, and up to 48 days after, starting
      dexamethasone. Maximum Doppler blood flow velocities from the left ventricular
      outflow tract (LVOT) were measured. RESULTS: Left ventricular hypertrophy (LVH)
      occurred in 29 babies (94%). Median hypertrophy of the IVSd in those receiving
      dexamethasone was 67% and LVPWd 56% of baseline measurements, significantly
      greater than control infants (p < 0.001). LVH appeared by a median of three days,
      peaking by a median of 10 days. All resolved by a median of 27 days. LVOT
      obstruction was not seen. There was no significant correlation with birthweight,
      gestation, blood pressure, or glucose tolerance. CONCLUSIONS: LVH developed in
      almost all preterm neonates receiving a 2-3 week course of dexamethasone, but was
      of little clinical importance and always resolved. Echocardiography is probably
      not required routinely in infants receiving such short course dexamethasone for
      chronic lung disease.

PMID- 9577286
TI  - Randomised controlled trial of eutectic mixture of local anaesthetics cream for
      venepuncture in healthy preterm infants.
AB  - AIM: To assess the safety and efficacy of EMLA cream (eutectic mixture of local
      anaesthetics) used to induce surface anaesthesia for venepuncture in healthy
      preterm infants. METHODS: Nineteen infants, median gestational age 31 weeks
      (range 26-33 weeks) were assessed in a randomised, double blind, placebo
      controlled, cross-over trial. Changes in physiological variables (heart rate,
      blood pressure, oxygen saturation) and behavioural responses (neonatal facial
      coding system score, crying time) before and after venepuncture with EMLA cream
      were compared with those obtained with a placebo cream to assess efficacy.
      Toxicity was assessed by comparing methaemoglobin concentrations at 1 hour and 8
      hours after application. RESULTS: There was no significant difference in efficacy
      between EMLA and placebo creams in physiological and behavioural responses. There
      was no significant difference in methaemoglobin concentrations one hour after the
      cream had been applied. At eight hours, however, concentrations were
      significantly higher after EMLA than placebo (p = 0.016). There was no evidence
      of clinical toxicity. CONCLUSION: This study does not support the routine use of
      EMLA for venepuncture in healthy preterm infants.

PMID- 9577287
TI  - Soluble L-selectin concentration in bronchoalveolar lavage fluid obtained from
      infants who develop chronic lung disease of prematurity.
AB  - AIMS: To explore the changes in neutrophil adhesion molecule expression and
      release into bronchoalveolar lavage fluid (BAL) obtained from infants who
      developed chronic lung disease (CLD). METHODS: BAL fluid was obtained from 37
      infants: 18 (median gestation 26 weeks, birthweight 835 g) who developed CLD, 12
      (29 weeks, 1345 g) with respiratory distress syndrome (RDS) and seven control
      infants (33 weeks, 2190 g). RESULTS: Soluble L-selectin (sL-selectin) in BAL
      fluid from the CLD and non-CLD groups was similar immediately after birth, but in
      infants who subsequently developed CLD, sL-selectin remained persistently
      increased (at day 7: CLD 42.6 vs RDS 6.0 ng/ml, p < 0.05; CLD vs controls 1.5
      ng/ml; p < 0.05). CD11b/CD18 expression on neutrophils obtained by BAL increased
      with time to reach a maximum at 17 days of age in infants who developed CLD.
      CONCLUSIONS: These results suggest that leucocyte traffic persists in infants who
      develop CLD and may have an important part to play in the pathogenesis of CLD.

PMID- 9577288
TI  - Volume delivery during high frequency oscillation.
AB  - AIM: To examine the delivered volume during "high volume strategy" high frequency
      oscillation, used as rescue treatment in preterm infants; and to identify
      factors, other than frequency and oscillatory amplitude, influencing the
      magnitude of volume delivery. METHOD: Twenty infants (median gestational age 29
      weeks) were studied on 45 occasions. Two oscillator types were used (SensorMedics
      and SLE). Delivered volume was measured under clinical conditions with the
      arterial blood gases within a predetermined range. A specially calibrated
      pneumotachograph system was used. RESULTS: Overall, the median delivered volume
      was 2.4 ml/kg (range 1.0 to 3.6 ml/kg); on 32 occasions the delivered volume was
      greater than 2.0 ml/kg and on seven greater than 3.0 ml/kg. The delivered volume
      related significantly to disease severity; there was an inverse correlaton
      between delivered volume and both the oxygenation index (OI) (r = -0.51) and
      AaDO2 (r = -0.54). CONCLUSION: Delivered volume during HFO may, in certain
      infants, exceed the anatomical dead space, permitting some direct alveolar
      ventilation.

PMID- 9577289
TI  - Long-term gastric pH monitoring for determining optimal dose of ranitidine for
      critically ill preterm and term neonates.
AB  - AIM: To determine the optimal doses of ranitidine for both preterm and term
      infants. METHOD: The effect of ranitidine treatment was measured from the long
      term intraluminal gastric pH in 16 preterm (gestational age under 37 weeks) and
      term infants treated in neonatal intensive care. The infants received three
      different bolus doses of ranitidine: 0.5 mg, 1.0 mg, and 1.5 mg per kilogram of
      body weight to keep the intraluminal gastric pH above 4 on a 24 hour basis.
      RESULTS: Critically ill neonates, including very low birth weight infants, were
      capable of gastric acid formation, and ranitidine treatment increased the
      intraluminal gastric pH. The effect of a single dose lasted longer in preterm
      than in term infants. The time needed for reaching the maximum gastric pH was
      significantly longer in preterm than in term infants. The ranitidine given
      correlated with the duration of increased gastric pH in a dose dependent manner
      both in preterm and term infants. CONCLUSION: Preterm infants need significantly
      smaller doses of ranitidine than term neonates to keep their intraluminal gastric
      pH over 4. The required optimal dose of ranitidine for preterm infants is 0.5
      mg/kg/body weight twice a day and that for term infants 1.5 mg/kg body weight
      three times a day.

PMID- 9577290
TI  - Francis Glisson (1597-1677) and the "discovery" of rickets.

PMID- 9577291
TI  - Unusual course of neonatal hyperinsulinaemic hypoglycaemia (nesidioblastosis)

PMID- 9577292
TI  - Informed consent for randomised controlled trials in neonates.

PMID- 9577293
TI  - Timing of surfactant treatment.

PMID- 9577294
TI  - Nasal deformities arising from flow driver continuous positive airway pressure.

PMID- 9577295
TI  - Nasal deformities at a UK hospital.

PMID- 9577296
TI  - Treatment of hypotension in very low birthweight infants.

PMID- 9577297
TI  - Alcohol, pregnancy and the Holy Bible.

PMID- 9577298
TI  - Tracheobronchomalacia in preterm infants.

PMID- 9577299
TI  - Estimating total body water in neonates.

PMID- 9577300
TI  - The remedying of iron deficiency: what priority should it have?
AB  - Fe deficiency is considered to be the commonest of nutritional deficiencies
      worldwide. Adverse effects are stated to include lower growth rate and impaired
      cognitive scores in children and poor pregnancy outcome and lower working
      capacity in adults. In the present review, Fe intake, stores of the element, the
      magnitude of deficiencies and the benefits from interventions, as reflected in
      the results of clinical trials, are discussed. Because of inadequacies of
      knowledge in numerous respects, more information is needed regarding the extent
      to which clinical trials relate to public health realities, before introducing
      regional or national supplementation programmes. While Fe supplements are needed
      in certain groups, and in particular regions, increased dietary intakes could be
      supplied by food fortification, as well as by individual improvements in intake.

PMID- 9577301
TI  - Excretion of endogenous and exogenous purine derivatives in sheep: effect of
      increased concentrate intake.
AB  - The present study examined the endogenous urinary excretion of purine derivatives
      (PD; allantoin, uric acid and xanthine plus hypoxanthine) in fed animals. Four
      Rasa Aragonesa ewes fitted with simple cannulas in the rumen and proximal
      duodenum were used. Animals were given a lucerne (Medicago sativa) hay diet, as
      sole feed (A) or supplemented, respectively, with 220 (B), 400 (C), and 550 (D) g
      rolled barley grain/d following a 4 x 4 random factorial design. Duodenal flow of
      purine bases (PB) was determined by the dual-phase marker system. 15N was infused
      continuously into the rumen to label exogenous or microbial PB. Duodenal PB flow
      and urinary excretion of PD increased with digestible organic matter intake
      showing a constant recovery of duodenal PB. The isotope dilution of PD in urine
      samples confirmed the presence of an endogenous fraction, originating from
      tissues, that increased from 115.2 (SE 5.84) mumol/kg W0.75 for the basal diet to
      304.2 (SE 7.6) mumol/kg W0.75 at the highest level of duodenal PB.

PMID- 9577302
TI  - Metabolic and cardiovascular responses to liquid and solid test meals.
AB  - There is indirect evidence from previous studies that the physiological responses
      to a liquid test meal may differ from those seen after consumption of a solid
      meal. The aim of the present study was to determine the metabolic and
      cardiovascular responses to isoenergetic high-carbohydrate mixed nutrient liquid
      or solid test meals, providing 2.1 MJ (approximately 70% of which was from
      carbohydrate), in eight healthy men following an overnight fast. Metabolic rate
      increased significantly after both meals (P < 0.0001, time effect), but the
      increase was significantly greater after the solid than after the liquid test
      meal (0.40 (SE 0.14), 0.26 (SE 0.10) kJ/min respectively, P = 0.001). The
      respiratory exchange ratio increased significantly after both the liquid and
      solid test meals, with no significant differences between them. Forearm blood
      flow increased significantly after the liquid test meal (0.70 (SE 0.33) ml/100 ml
      per min, P < 0.0001), whilst it decreased after the solid meal (-0.28 (SE 0.16)
      ml/100 ml per min, P < 0.0001). Heart rate increased on both occasions, but the
      response was significantly greater after the solid meal (P = 0.02). There were no
      significant plasma noradrenaline responses, but there were significantly higher
      increases in serum insulin and blood glucose following the solid meal. Thus, the
      physical form of a test meal affects the physiological responses to nutrient
      ingestion.

PMID- 9577303
TI  - The determinants of iron status in early pregnancy.
AB  - In pregnancy, the additional demands for Fe are thought to be met principally
      through increased maternal dietary Fe absorption and by mobilization of maternal
      Fe stores. In a general population sample of 576 women we examined the maternal
      and dietary characteristics which influenced Fe stores (assessed by serum
      ferritin concentration) in early pregnancy. The effects of these characteristics
      on two measures of functional Fe status (mean cell volume and haemoglobin
      concentration) were also considered. Serum ferritin concentrations were lower in
      multiparous women (P < 0.0001) and in those with a lower BMI (P = 0.01), and rose
      with increasing alcohol intake (P < 0.0001). Ferritin concentrations fell with
      increasing Ca intake (P < 0.0001); the proportion of women with serum ferritin
      values < or = 12 micrograms/l rose from 14% of the women in the lowest quarter of
      Ca intake to 29% of the women in the highest quarter. Mean cell volume and
      haemoglobin concentration were not related to Ca intake in early pregnancy.
      Although Ca added to test-meals reduces Fe absorption, long-term Ca
      supplementation has not been shown to lower plasma ferritin concentration,
      suggesting that high habitual Ca intakes would be unlikely to influence Fe status
      in non-pregnant individuals. Our findings show that in early pregnancy there is
      an association between high dietary Ca intake and lower Fe stores. This effect of
      Ca on one aspect of Fe status may result from its influence on Fe
      bioavailability.

PMID- 9577304
TI  - Is zinc a limiting nutrient in the diets of rural pregnant Malawian women?
AB  - Pregnant women consuming plant-based diets are at risk of Zn deficiency; Zn
      requirements for fetal growth and maternal tissue accretion are high. Therefore
      we have studied, at 24 and 33 weeks gestation, the Zn status of eighty-seven
      pregnant rural Malawian women (mean age 22.7 years) who consume maize-based
      diets, using anthropometry, dietary intake data, plasma and hair Zn
      concentrations, and infection status via serum C-reactive protein, leucocyte
      count, and malaria blood smear. Of the women, 12% were stunted (height-for-age Z
      score < -2 SD) and 20% lost weight over the 9-week period; weight gain averaged
      0.13 kg/week. Mean plasma Zn concentration declined significantly from 24 to 33
      weeks (7.9 (SD 2.2) v. 6.6 (SD 2.0) mumol/l; P < 0.0003). Both plasma and hair Zn
      values were very low; nearly 50% of the women had both plasma and hair Zn values
      below acceptable cut-off values. No significant differences in biochemical Zn
      indices existed between those who tested positive and negative for infection.
      Cereals (mainly maize) provided more than two-thirds of mean energy intake
      compared with less than 5% from flesh foods. As a result about 60% of the
      subjects had dietary phytate:Zn molar ratios greater than 15, and more than 35%
      had inadequate Zn intakes based on probability estimates and WHO basal
      requirements. Biochemical evidence of Zn deficiency was attributed in part to low
      intakes of poorly available Zn. The anthropometric, biochemical, and dietary data
      together indicate that Zn deficiency may be a factor limiting pregnancy outcome
      in rural Malawian women.

PMID- 9577305
TI  - The influence of live weight, live-weight change and diet on protein synthesis in
      the skin and skeletal muscle in young Merino sheep.
AB  - Wool growth is derived directly from protein synthesis in the skin of sheep, and
      is affected by the nutritional status of the animals. The present experiment
      examined both protein synthesis in the skin and muscle and wool growth in Merino
      lambs differing in live weight, intake and dietary protein source. The experiment
      was a 2(3) factorial design: twenty-four 5-month-old lambs initially weighing 33
      kg (heavy) or 25 kg (light) were fed on a hay-based diet with either lupin seed
      or rapeseed meal as the major protein sources to maintain live weight (M) for 56
      d, or were fed at 0.6 M for 28 d (period 1) followed by 28 d at 1.6 M (period 2).
      Fractional protein synthesis rates (FSR, % per d) in the skin and the m.
      longissimus dorsi on days 4 and 24 of period 1 and day 4 of period 2 were
      measured by means of a flooding dose of L-[ring-d5]phenylalanine, and wool growth
      on a skin patch over period 1 was also measured. The FSR ranged from 13.2 to
      20.2% per d in the skin, higher than reported for other breeds, and 1.53-3.07%
      per d in the muscle. Sheep on the low intake (0.6 M) had significant reductions
      in FSR, protein content (g), protein synthesis (g/d) in the skin, and wool growth
      (g/d). The heavy lambs had similar FSR to the light lambs, but had a higher skin
      protein content and total protein synthesis per unit of skin area (100 cm2) and,
      therefore, grew more wool. The rapeseed-meal diet increased FSR and wool growth
      only in the light lambs over the short term. The protein deposited in wool over
      period 1 was 0.185 of the total protein synthesis in the skin, regardless of live
      weight, intake or diet, a result similar to other breeds. With the changes in
      dietary intake, protein synthesis in the skin and muscle responded
      differentially, with nutrient partitioning at sub-maintenance in favour of wool
      growth but at supra-maintenance, following a nutrient restriction, in favour of
      weight gain in young growing sheep.

PMID- 9577306
TI  - The interaction between nutritional status and growth hormone in young cattle:
      differential responsiveness of fat and protein metabolism.
AB  - The effect of dietary intake level on in vivo plasma leucine and plasma palmitate
      flux rates and on the response to a bolus injection of bovine growth hormone (GH)
      was investigated in six young steers. Animals were fed on a pelleted diet of
      dried grass-barley (0.7:0.3, w/w) in quantities sufficient to supply 0.8, 1.2,
      1.6, 2.0, 2.4 or 2.65 x maintenance energy requirement, offered in hourly
      portions. Continuous intravenous infusions of [1-13C]leucine or [1-13C]palmitate
      were used to determine the flux of amino acid and fatty acid through the plasma
      pool before, immediately (1-3 h) after and 22-24 h after a subcutaneous injection
      of bovine GH (0.55 mg/kg body weight). Hourly blood samples were taken for 27 h
      to monitor the temporal responses of circulating hormones and metabolites
      following GH administration. The animal on the lowest plane of nutrition had
      elevated plasma GH and reduced insulin-like growth factor-1 concentrations
      compared with those fed on higher intake levels. Plasma leucine flux and leucine
      concentration increased with intake while palmitate flux and plasma non
      esterified fatty acid (NEFA) concentrations were inversely related to intake.
      Leucine flux rate decreased in the animals fed on the two highest intake levels
      in response to GH 22-24 h after administration, but plasma leucine concentrations
      were reduced in all animals at this time. Only the animal fed on the lowest
      intake level showed an immediate response to GH (within 3 h of administration)
      with increased palmitate flux and plasma NEFA concentrations but a lipolytic
      response was apparent in other animals 22-24 h post-administration although the
      magnitude of the response was markedly reduced at high intakes. We conclude that
      lipid and protein metabolism are differentially responsive to GH and nutritional
      status.

PMID- 9577307
TI  - Periodic fluctuations of gut regulatory peptides in phase with the duodenal
      migrating myoelectric complex in preruminant calves: effect of different sources
      of dietary protein.
AB  - Four preruminant calves with implanted electrodes in the duodenum and a catheter
      in the external jugular vein were used for investigation of plasma gut regulatory
      peptide profiles during different phases of migrating myoelectric complex (MMC)
      in the small intestine. The effects of different dietary proteins on the rhythmic
      activity of gut peptides and gastrointestinal motility were compared. In
      particular, the effects of skimmed-milk protein (retaining physiological patterns
      of abomasal clotting, and abomaso-intestinal digesta flow) v. fish protein
      (devoid of clotting activity and modifying the digesta flow) were studied. In
      calves fed on the milk diet, plasma concentrations of pancreatic polypeptide,
      motilin, secretin, cholecystokinin (CCK) and somatostatin, but not vasoactive
      intestinal polypeptide or gastrin, fluctuated in phase with the duodenal MMC in
      the preprandial period. Feeding transiently affected the intestinal MMC and
      abolished the peptide fluctuations in a specimen-specific manner. In contrast,
      calves fed on the fish-protein diet showed more profound changes in intestinal
      MMC. In these animals the MMC-related fluctuations were significant only for
      plasma CCK. In conclusion, the source of dietary protein has an impact on the
      physiological endocrine function of the small intestine. Observed fluctuations of
      plasma gut regulatory peptides seem to be secondary to duodenal motility cycles.

PMID- 9577308
TI  - Effect of glucocorticoid excess on skeletal muscle and heart protein synthesis in
      adult and old rats.
AB  - This study was carried out to analyse glucocorticoid-induced muscle wasting and
      subsequent recovery in adult (6-8 months) and old (18-24 months) rats because the
      increased incidence of various disease states results in hypersecretion of
      glucocorticoids in ageing. Adult and old rats received dexamethasone in their
      drinking water for 5 or 6 d and were then allowed to recover for 3 or 7 d. As
      dexamethasone decreased food intake, all groups were pair-fed to dexamethasone
      treated old rats (i.e. the group that had the lowest food intake). At the end of
      the treatment, adult and old rats showed significant increases in blood glucose
      and plasma insulin concentrations. This increase disappeared during the recovery
      period. Protein synthesis of different muscles was assessed in vivo by a flooding
      dose of [13C]valine injected subcutaneously 50 min before slaughter.
      Dexamethasone induced a significant decrease in protein synthesis in fast-twitch
      glycolytic and oxidative glycolytic muscles (gastrocnemius, tibialis anterior,
      extensor digitorum longus). The treatment affected mostly ribosomal efficiency.
      Adult dexamethasone-treated rats showed an increase in protein synthesis compared
      with their pair-fed controls during the recovery period whereas old rats did not.
      Dexamethasone also significantly decreased protein synthesis in the predominantly
      oxidative soleus muscle but only in old rats, and increased protein synthesis in
      the heart of adult but not of old rats. Thus, in skeletal muscle, the catabolic
      effect of dexamethasone is maintained or amplified during ageing whereas the
      anabolic effect in heart is depressed. These results are consistent with muscle
      atrophy occurring with ageing.

PMID- 9577309
TI  - Glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1)
      activities in riboflavin-deficient rats infected with Plasmodium berghei malaria.
AB  - Riboflavin deficiency interferes with the growth and multiplication of malaria
      parasites as well as the host response to malaria. The objective of the present
      work was to determine the effects of riboflavin deficiency on erythrocyte
      glutathione peroxidase (EC 1.11.1.9; GPx) and superoxide dismutase (EC 1.15.1.1;
      SOD) in rats infected with Plasmodium berghei malaria. Riboflavin in its co
      enzyme form, FAD, is required by glutathione reductase (EC 1.6.4.1) to regenerate
      GSH and GSH is an important cellular antioxidant both in its own right and also
      as a substrate for the enzyme GPx. Weanling rats were deprived of riboflavin for
      8 weeks before intraperitoneal injection of 1 x 10(6) P. berghei parasites.
      Control animals were weight-matched to the respective riboflavin-deficient group.
      At 10 d post-infection, parasite counts were higher in the weight-matched control
      group than the riboflavin-deficient group (P = 0.004). GPx activity was higher in
      erythrocytes of rats parasitized with P. berghei than comparable non-infected
      rats regardless of riboflavin status (P < 0.05). As mature erythrocytes do not
      synthesize new protein, the higher GPx activities were probably due to the
      presence of the parasite protein. In erythrocytes from riboflavin-deficient rats,
      GPx activity tended to be lower than in those rats fed on diets adequate in
      riboflavin (weight-matched controls) whether parasitized or not, but the
      difference was not significant. Neither riboflavin deficiency nor malaria had any
      effect on erythrocyte SOD activity. It was concluded that riboflavin deficiency
      has no marked effect on erythrocyte GPx or SOD activity in the rat.

PMID- 9577310
TI  - Cephalic vein in salvage microsurgical reconstruction in the head and neck.
AB  - Free tissue transfers have significantly improved the outcome of major head and
      neck reconstruction. In some situations of microvascular tissue transfer,
      adequate recipient veins are not available for flap venous outflow. This may
      result from a variety of reasons, including prior radical neck dissection,
      radiation therapy, and inflammatory changes from severe trauma. We report our
      experience using cephalic vein transposition in 11 such patients with unavailable
      local veins for free flap reconstruction. In all cases the cephalic vein provided
      reliable and adequate outflow for the tissue transfers. Our experience suggests
      that the cephalic vein transposition offers certain advantages, obviating the use
      of vein grafts: 1. It requires only one venous anastomosis; 2. A long pedicle can
      be harvested to reach the mid-face or contralateral neck without undue tension;
      3. The cephalic-subclavian system is a high-flow, low-pressure system; 4. This
      vein is located outside ablative surgical field, or radiated tissue, and
      therefore undamaged; 5. The vein calibre is well suited for microsurgical
      anastomosis.

PMID- 9577311
TI  - A quantitative method for the assessment of facial rejuvenation: a prospective
      study investigating the carbon dioxide laser.
AB  - Laser resurfacing has been reported to have a useful role in the treatment of
      facial rhytides, however the results of published series have relied on
      subjective methods of assessment. The aim of this investigation was to develop an
      accurate method of measuring wrinkle depth and secondly to use this to assess the
      efficacy of laser rejuvenation. Wrinkle depth was measured in 30 patients with
      perioral rhytides using a silicone mask to provide a negative replica. Depth was
      measured using simple light microscopy and the accuracy of this was confirmed
      with the electron microscope. A highly significant correlation was found between
      these two methods of measurement (R2 = 0.97, P < 0.0001) with an accuracy of 0.03
      mm. Using this method laser rejuvenation was evaluated in a prospective series of
      30 patients with perioral rhytides (median follow-up 11.5 months, range 5-20
      months). Resurfacing was found to achieve a significant reduction in mean wrinkle
      depth of 91% (paired t-test, P < 0.00001). The only complication reported was
      erythema which was always transient. The use of light microscopy on silicone
      moulds therefore provides a simple and accurate method for assessing the outcome
      of facial rejuvenation. Using this technique, the carbon dioxide laser was
      objectively found to provide a safe and effective treatment for facial rhytides.

PMID- 9577312
TI  - Reconstruction of non-marginal ear defect by a postauricular wedge transposition
      flap.

PMID- 9577313
TI  - Surgical reconstruction in cryptophthalmos.
AB  - Cryptophthalmos is the congenital absence of the eyelid with skin passing
      continuously from the forehead onto the cheek over a malformed eye. The deformity
      can be classified into three types: complete, incomplete and abortive. We present
      the cases of two siblings, each with incomplete cryptophthalmos involving one
      eye. We report a three-stage reconstructive procedure in which a conchal
      cartilage 'sandwich' graft was first placed between the skin flap and the globe,
      mucous membrane subsequently grafted onto the inner surface of the cartilage
      graft, and lid level adjusted as the third stage.

PMID- 9577314
TI  - Successful treatment of a giant congenital melanocytic naevus with the high
      energy pulsed CO2 laser.

PMID- 9577315
TI  - Deep inferior epigastric artery (DIEA) skin flap: clinical experience of 15
      cases.
AB  - Skin flaps devoid of rectus muscle, raised on a single musculocutaneous
      perforator (14 cases), and on two musculocutaneous perforators (1 case) of the
      deep inferior epigastric artery (DIEA) were used in 14 patients to cover various
      defects during a period of 3 years. The flaps were raised on the perforator
      arising slightly lateral to the centre of the muscle below the umbilicus, which
      is a sub-branch of the lateral branch of DIEA. The defects were located on the
      upper limb in four, the lower limb in nine, and the scalp and forehead in the
      remaining two cases. In one patient, the flap was preexpanded for 4 weeks prior
      to transfer. The longest flap was 40 x 12 cm, and the widest flap was 30 x 18 cm
      in dimension. All donor defects were closed primarily. Two flaps were lost due to
      venous thrombosis on the fourth postoperative day. Tip necrosis was observed in
      two flaps, both of which were salvaged from venous thrombosis at 36 hours and 5
      days postoperatively. The remaining 11 flaps survived completely. The DIEA skin
      flap was found to provide the following benefits: (1) the largest available skin
      flap where the donor site could be closed primarily; (2) decreased possibility of
      abdominal wall weakness and hernia formation; and (3) potential of obtaining a
      thin flap either by trimming of the subcutaneous fat or by preexpansion.

PMID- 9577316
TI  - Hereditary multiple glomangiomas.
AB  - Hereditary multiple glomangiomas are an interesting rare problem which can either
      present as multiple painful cutaneous lesions or, rarely, a cosmetic challenge
      due to site, size or number of lesions. It may also pose a diagnostic dilemma,
      which can only be settled by biopsy. Malignant change in glomangioma is extremely
      rare and only a few cases are well documented in literature. A case report of
      this condition, along with extensive review of the literature, is presented. The
      prognosis of various forms of glomangiomas and efficacy of diagnostic and
      therapeutic tools is discussed.

PMID- 9577318
TI  - Obstetrical brachial palsy.
AB  - Obstetrical brachial palsy (OBP) (also known in its various forms as Erb's palsy,
      Klumpke's paralysis, Erb-Duchenne palsy) complicates a very small proportion of
      births. Furthermore it seems likely that many cases recover with little in the
      way of remaining deficit but it is equally certain that some cases will not
      recover. There is increasing evidence that microsurgical help at an early stage
      can improve the prognosis in some cases. Scepticism exists about the role of
      surgery and many cases are referred too late for primary nerve surgery.
      Specialist surgical advice, specialist physiotherapy and where appropriate,
      either early nerve surgery or secondary reconstructive procedures at a later date
      can improve the condition of many of these children. This review condenses many
      of the current opinions and highlights areas of developing knowledge and debate.

PMID- 9577317
TI  - Endoscopically-assisted adipofascial flap harvest for soft tissue defects of the
      lower leg.
AB  - Five cases of soft tissue defect of the lower leg were reconstructed successfully
      with the distally based medial adipofascial flap which was harvested with
      endoscopically-assisted surgery. The size of these flaps ranged from 4.0 x 7.0 cm
      to 5.0 x 15.0 cm in size. All the flaps had good perfusion and uneventful course
      postoperatively. The donor site skin was intact except for an additional access
      scar 2.5 cm in length. The donor site morbidity of the adipofascial flap was
      further minimised in this series.

PMID- 9577319
TI  - Predicting the outcome of laser treatment for pigmented lesions.
AB  - Laser treatment of pigmented lesions requires melanocytes to lie within the range
      of penetration of the laser, and to contain melanin in order to absorb and covert
      light energy into heat by photothermolysis. This study investigated whether these
      limitations could be tested by immunohistology and used to predict the outcome of
      treatment. Punch biopsies were taken from 32 patients prior to laser treatment.
      Immunohistology targeting the S-100 antigen allowed measurement of melanocytic
      depth and the presence of amelanosis. These parameters provided an accurate
      method of predicting good results (sensitivity 81%, specificity 93%) and were
      particularly useful in delineating the likelihood of a poor/very poor outcome
      (sensitivity 100%), even beyond the predictive capacity of the test patch. No
      complications were associated with the biopsy technique which reliably provided
      sufficient material for histological assessment. This study reports the clinical
      applications of this test to laser treatment.

PMID- 9577320
TI  - Venous thrombosis in a replanted finger with underlying factor V Leiden mutation.
AB  - Resistance to activated protein C (APC resistance) was described recently as a
      cause for thrombophilia. APC inactivates coagulation co-factors Va and VIIIa. A
      single base-pair mutation changing Arg506 to Gln at the APC cleavage site of the
      factor V gene leads to a factor V Leiden variant, which is the most frequent
      cause of APC resistance. Recently, its role in peripheral venous thrombosis
      during pregnancy was described. We here report a case with thrombosis of the
      venous anastomoses after finger replantation with resistance to activated protein
      C associated with factor V Leiden mutation.

PMID- 9577321
TI  - Cellular proliferation characteristics do not account for the behaviour of
      horrifying basal cell carcinoma. A comparison of the growth fraction of
      horrifying and non horrifying tumours.
AB  - This study compared the clinical features, histological subtype, growth fraction
      (by Ki67 immunohistochemistry) and proliferation pattern of 22 clinically defined
      horrifying basal cell carcinoma compared to 81 non horrifying lesions. Late
      presentation was associated with half of the horrifying tumours. The other half
      developed horrifying tumours despite early intervention. The horrifying tumours
      exhibited a variety of histological growth patterns. A total of 50% were
      infiltrative, 23% nodular and 18% micronodular. There was no difference in the
      growth fraction or proliferation pattern between horrifying and non horrifying
      tumours of similar growth pattern (P = ns), although infiltrative tumours in
      either group exhibited a significantly higher growth fraction than nodular
      tumours (P < 0.01). This suggests that there is no intrinsic biological
      difference between horrifying and non horrifying tumours to account for their
      behaviour. We conclude that late presentation, failed or inadequate early
      management especially of infiltrative tumours (and other subtypes) determines the
      development of horrifying tumours.

PMID- 9577322
TI  - Hyperbaric oxygen therapy for deep second degree burns: an experimental study in
      the guinea pig.
AB  - Most previous animal studies reporting improved epithelialisation and healing of
      burn wounds under hyperbaric oxygen (HBO) did not include the conventional
      treatment with topical antibiotics as part of the protocol, and did not compare
      the effectiveness of HBO therapy with that of normobaric 100% oxygen (NO). The
      purpose of our study was to compare the results of combined treatment with HBO +
      silver sulfadiazine (SS) and those of treatment with NO + SS or SS alone. Deep
      second degree burns were produced on the depilated backs of 54 guinea pigs using
      a validated burn protocol. The animals were assigned to three treatment groups:
      HBO + SS, NO + SS, and SS. Dressings were changed daily. HBO was administered at
      2 atmospheres absolute (ATA) for 90 min BID, and NO for 90 min BID. The
      parameters compared among the groups were laser Doppler flowmetry, and burn wound
      contracture and re-epithelialisation data derived from computerised planimetry of
      photographs of the wound. No differences in laser Doppler flowmetry results or
      the magnitude of contracture were found between the groups. Significantly
      increased re-epithelialisation was observed under NO + SS starting 10 days after
      the burn (P = 0.02, ANOVA). This significance stems from the difference between
      the HBO + SS and NO + SS groups (Tukey test). These data indicate that
      excessively high levels of tissue PO2 might compromise burn healing, and explain
      our results. A further study comparing combined treatment using a milder HBO
      protocol + SS and NO + SS is indicated in the search for the optimal HBO regimen.

PMID- 9577323
TI  - Plastic surgical training and the Internet: how plastic surgeons learn.

PMID- 9577324
TI  - Rhinoscleroma: an interesting differential diagnosis.

PMID- 9577325
TI  - The use of negative pressure to promote healing.

PMID- 9577326
TI  - Measuring patient-based outcomes in a plastic surgery service: breast reduction
      surgical patients.

PMID- 9577327
TI  - Inflammatory bowel disease incidence: up, down or unchanged?

PMID- 9577328
TI  - Oesophageal pain in coronary artery disease.

PMID- 9577329
TI  - Nitric oxide as an antimicrobial agent: does NO always mean NO? [ comment].

PMID- 9577331
TI  - Feeding the inflamed pancreas.

PMID- 9577330
TI  - Capsaicin sensitivity and epidermal growth factor.

PMID- 9577332
TI  - Octreotide in hepatocellular carcinoma.

PMID- 9577333
TI  - Gastro-oesophageal reflux: does it matter what you eat?

PMID- 9577334
TI  - The alpha-smooth muscle actin promoter: a useful tool to analyse autocrine and
      paracrine roles of mesenchymal cells in normal and diseased bowel.
AB  - Smooth muscle cells (SMC) of the vascular wall, bladder, myometrium, and
      gastrointestinal and respiratory tracts retain the ability to proliferate
      postnatally, which enables adaptive responses to injury, hormonal, or mechanical
      stimulation. SMC growth is regulated by a number of mesenchymal growth factors,
      including insulin-like growth factor I (IGF-I). To explore the function of IGF-I
      on SMC in vivo, the mouse SMC alpha-actin promotor fragment SMP8 (-1074 bp, 63 bp
      of 5'UT and 2.5 kb of intron 1) was cloned upstream of rat IGF-I cDNA, and the
      fusion gene microinjected into fertilized eggs of the FVB-N mouse strain. Mating
      of hemizygous mice with controls produced about 50% transgenic offspring, with
      equal sex distribution. Transgenic IGF-I mRNA expression was confined to SMC
      containing tissue, with the following hierarchy: bladder > stomach > aorta =
      uterus > intestine. There was no transgene expression in skeletal muscle, heart,
      or liver. Radioimmunoassayable IGF-I content was increased by 3.5- to 4-fold in
      aorta, and by almost 10-fold in bladder of transgenic mice at 5 and 10 wk, with
      no change in plasma IGF-I levels. Wet weight of bladder, stomach, intestine,
      uterus, and aorta was selectively increased, with no change in total body or
      carcass weight of transgenic animals. In situ hybridization showed that transgene
      expression was exquisitely targeted to the smooth muscle layers of the arteries,
      veins, bladder, ureter, stomach, intestine, and uterus. Paracine overproduction
      of IGF-I resulted in hyperplasia of the muscular layers of these tissues,
      manifesting in remarkably different phenotypes in the various SMC beds. Whereas
      the muscular layer of the bladder and stomach exhibited a concentric thickening,
      the SMC of the intestine and uterus grew in a longitudinal fashion, resulting in
      a marked lengthening of the small bowel and of the uterine horns. This report
      describes the first successful targeting of expression of any functional protein
      capable of modifying the phenotype of SMC in transgenic mice. IGF-I stimulates
      SMC hyperplasia, leading to distinct patterns of organ remodeling in the
      different tissue environments.

PMID- 9577335
TI  - A prospective study of oesophageal function in patients with normal coronary
      angiograms and controls with angina.
AB  - AIMS: To compare the incidence of oesophageal abnormalities and their correlation
      with chest pain in patients with normal coronary angiograms, and in controls with
      angina. PATIENTS: Sixty one patients with normal coronary angiograms (NCA group)
      referred to a single cardiac centre between March 1990 and April 1991; 25 matched
      controls with confirmed coronary artery disease (CAD group). SETTING: Cardiac
      referral centre and oesophageal function testing laboratory. MAIN OUTCOME
      MEASURES: Oesophageal manometry, provocation tests, and 24 hour ambulatory pH
      monitoring. RESULTS: Simultaneous contractions were more common (6.7% versus
      0.8%, p < 0.01), and the duration of peristaltic contractions was longer (2.9
      versus 2.4 seconds, p < 0.01) in the NCA group than in the CAD group. There were
      no group differences in the amplitude of peristaltic contractions, and none had
      nutcracker oesophagus. Ten (16%) patients with NCA and no patients with CAD had
      diffuse spasm (p = 0.03). Twenty one (34%) patients with NCA, and five (20%)
      patients with CAD had abnormal gastro-oesophageal reflux (p > 0.05). There was no
      significant difference between the groups in the number of patients whose pain
      was temporally related to pH events. Particular chest pain characteristics, or
      the presence of additional oesophageal symptoms, were not predictive of an
      oesophageal abnormality. CONCLUSION: Oesophageal function tests commonly
      implicate the oesophagus as a source of pain in patients with normal coronary
      angiograms. With the exception of simultaneous contractions during manometry
      however, the incidence of abnormalities and in particular the correlation of pH
      events with chest pain are as common in patients with normal coronary angiograms
      as in controls with angina. The oesophagus may often be an unrecognised source of
      pain in both groups of patients.

PMID- 9577336
TI  - Effect of increasing the fat content but not the energy load of a meal on gastro
      oesophageal reflux and lower oesophageal sphincter motor function.
AB  - BACKGROUND: Although fatty foods are commonly considered detrimental in patients
      with reflux disease, no objective data exist that substantiate this belief. AIMS:
      To investigate the effect of fat on gastro-oesophageal reflux and lower
      oesophageal sphincter (LOS) motor activity. SUBJECTS: Thirteen healthy subjects
      and 14 patients with reflux disease. METHODS: Oesophageal pH, LOS, and
      oesophageal pressures were recorded for 180 minutes after a high fat (52% fat)
      and a balanced (24% fat) meal (both 3.18 MJ) on two different occasions. Eight
      controls and seven patients were studied in the recumbent position and the others
      in the sitting position. RESULTS: The percentage of time at pH less than 4 and
      the rate of reflux episodes were higher (p < 0.01) in the patients than in the
      healthy subjects (mean 14.1% versus 1.7% and 4.4/h versus 0.8/h respectively), as
      was the percentage of transient LOS relaxations associated with reflux (62%
      versus 32%, p < 0.01). The high fat meal did not increase the rate of reflux
      episodes nor exposure to oesophageal acid in either group regardless of body
      posture. The rate of transient LOS relaxations, their association with reflux,
      and basal LOS pressure were also unaffected. CONCLUSIONS: Increasing fat intake
      does not affect gastro-oesophageal reflux or oesophagogastric competence for at
      least three hours after a meal.

PMID- 9577337
TI  - Helicobacter pylori is killed by nitrite under acidic conditions.
AB  - BACKGROUND: Due to the expression of urease, Helicobacter pylori is able to
      establish itself in the human stomach under acidic conditions. A novel host
      defence mechanism was recently proposed, suggesting that the formation of
      salivary nitrite in symbiosis with facultative anaerobic bacteria in the
      oropharynx, is aimed at enhancing the antimicrobial activity of gastric juice.
      AIMS: To investigate whether the addition of nitrite in physiological
      concentrations influences the resistance of H pylori to acid. METHODS: H pylori
      cultured from fresh gastric Biopsy specimens was exposed for 30 minutes to normal
      saline and to HCl/KCl buffer (0.2M) at pH 2 with urea (5 mM) added. The influence
      of potassium nitrite (50-1000 mumol/l) on bacterial survival was determined.
      RESULTS: Addition of nitrite (1 mM) to acidic solutions (pH 2) resulted in
      complete kill of H pylori within 30 minutes exposure time whereas acid alone
      allowed the organism to survive (p < 0.001). The antimicrobial effect of nitrite
      at pH 2 against H pylori was dose dependent and complete kill of organisms
      occurred at concentrations > or = 500 mumol/l. CONCLUSION: Acidified nitrite has
      anti-bacterial activity against H pylori. This should prompt further research
      into the effect of salivary nitrite on the survival of H pylori in the human
      stomach.

PMID- 9577338
TI  - Major virulence factors, VacA and CagA, are commonly positive in Helicobacter
      pylori isolates in Japan.
AB  - BACKGROUND: VacA and CagA proteins have been reported to be major virulence
      factors of Helicobacter pylori. However, antibodies against these proteins are
      frequently found in the sera of Japanese patients regardless of their
      gastroduodenal status. AIM: To evaluate the expression of VacA and CagA proteins
      by H pylori strains isolated in Japan. METHODS: By using specific antibodies
      raised against recombinant VacA and CagA proteins, the expression of VacA and
      CagA was evaluated in 68 H pylori strains isolated from Japanese patients; a
      vacuolating assay and genotyping of the vacA gene were also used in the
      evaluation. The results in analysed in relation to the gastroduodenal diseases of
      the hosts. RESULTS: VacA and CagA proteins were expressed in 59/68 (87%) and in
      61/68 (90%) isolates respectively. The vacuolating assay was positive in 57/68
      (84%) isolates, indicating that most immunologically VacA positive strains
      produced active cytotoxin. The prevalence of infection with strains expressing
      CagA and positive for vacuolating activity (Type I) was very high, 54/68 (79%),
      irrespective of the gastroduodenal status of the host. CONCLUSION: Most H pylori
      isolates in Japan are positive for vacuolating cytotoxin and CagA, and thus these
      virulence factors cannot be used as markers to discern the risk of developing
      serious gastroduodenal pathologies in the hosts. However, the high prevalence of
      infection with strains positive for vacuolating cytotoxin and CagA may contribute
      to the characteristics of H pylori infection in Japan.

PMID- 9577339
TI  - Role of capsaicin sensitive nerves in epidermal growth factor effects on gastric
      mucosal injury and blood flow.
AB  - BACKGROUND: Epidermal growth factor (EGF) and capsaicin protect against
      experimental gastric mucosal injury. Capsaicin exerts its gastroprotective effect
      by stimulating afferent neurones leading to release of calcitonin gene related
      peptide (CGRP) which causes gastric hyperaemia. EGF also causes gastric
      hyperaemia but whether it acts via capsaicin sensitive neurones is unknown. AIMS:
      To assess the influence of: (1) capsaicin desensitisation on EGF effects on
      gastric mucosal injury and gastric mucosal blood flow: and (2) close arterial
      infusion of hCGRP8-379, a CGRP antagonist, on EGF effects on gastric mucosal
      blood flow. METHODS: The absolute ethanol induced gastric mucosal injury model in
      the rat was used. Gastric mucosal damage was assessed by planimetry and light
      microscopy. Gastric mucosal blood flow was measured by laser Doppler flowmetry in
      a gastric chamber preparation. RESULTS: Capsaicin desensitisation abolished the
      gastroprotective and gastric hyperaemic effects of EGF. Close arterial infusion
      of hCGRP8-37 antagonised the hyperaemic effect of both capsaicin and EGF.
      CONCLUSION: Results show that EGF may exert its gastroprotective and gastric
      hyperaemic effects via capsaicin sensitive afferent neurones.

PMID- 9577340
TI  - Oxidative DNA damage accumulation in gastric carcinogenesis.
AB  - BACKGROUND: Gastric carcinogenesis is a multifactorial, multistep process, in
      which chronic inflammation plays a major role. AIMS: In order to ascertain
      whether free radical mediated oxidative DNA damage is involved in such a process,
      concentrations of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic/carcinogenic
      adduct, and thiobarbituric acid reactive substances (TBARS), as an indirect
      measure of free radical mediated damage, were determined in biopsy specimens from
      patients undergoing endoscopy. PATIENTS: Eighty eight patients were divided into
      histological subgroups as follows: 27 with chronic non-atrophic gastritis, 41
      with atrophic gastritis, six with gastric cancer, and 14 unaffected controls.
      METHODS: Intestinal metaplasia, Helicobacter pylori infection, and disease
      activity were semiquantitatively scored. 8OHdG concentrations were assessed by
      HPLC with electrochemical detection, and TBARS concentrations were
      fluorimetrically assayed. RESULTS: 8OHdG concentrations (mean number of
      adducts/10(5) dG residues) were significantly higher in chronic atrophic
      gastritis (p = 0.0009). Significantly higher concentrations were also detected in
      the presence of severe disease activity (p = 0.02), intestinal metaplasia (p =
      0.035), and H pylori infection (p = 0.001). TBARS concentrations were also higher
      in atrophic gastritis, though not significantly so. In a multiple logistic
      regression analysis, 8OHdG concentrations correlated best with the presence and
      severity of H pylori infection (r = 0.53, p = 0.002). CONCLUSION: Chronic
      gastritis is characterised by the accumulation of oxidative DNA damage with
      mutagenic and carcinogenic potential. H pylori infection is the major determinant
      for DNA adduct formation.

PMID- 9577341
TI  - Increased immunoglobulin G production by short term cultured duodenal biopsy
      samples from HIV infected patients.
AB  - BACKGROUND: Secretory immunity is a major defence mechanism against infections at
      mucosal surfaces which are common in HIV infected patients. AIMS: To analyse
      intestinal immunoglobulin production in HIV infection in comparison with that in
      saliva and serum. PATIENTS AND METHODS: Immunoglobulin G (IgG), A (IgA), and M
      (IgM) concentrations were determined in supernatants of short term cultured
      duodenal biopsy samples, serum, and saliva from HIV infected patients (n = 28)
      and controls (n = 14) by radial immunodiffusion. RESULTS: IgG was increased in
      the supernatants of short term cultured biopsy samples and saliva from HIV
      infected patients compared with controls (p < 0.01), but IgA and IgM levels were
      normal. In contrast, both IgG and IgA concentrations in serum were higher in HIV
      infected patients than in controls (p < 0.002). No correlation was found between
      IgA produced by duodenal biopsy specimens and serum IgA. CONCLUSION:
      Abnormalities in mucosal immunoglobulin production in HIV infection were
      surprisingly small, indicating that specific secretory immunity rather than
      quantitative immunoglobulin production may be impaired. However, increased
      production of IgG could contribute to mucosal inflammation by complement
      activation. Our findings of normal mucosal IgA production and the lack of
      correlation between serum and mucosal IgA argues against an intestinal origin for
      the increased serum IgA levels in HIV infected patients.

PMID- 9577342
TI  - Prevalence and clinical features of selective immunoglobulin A deficiency in
      coeliac disease: an Italian multicentre study. Italian Society of Paediatric
      Gastroenterology and Hepatology (SIGEP) and "Club del Tenue" Working Groups on
      Coeliac Disease.
AB  - BACKGROUND: Selective immunoglobulin A (IgA) deficiency (SIgAD) is associated
      with coeliac disease (CD). AIM: To make a retrospective study of the association
      of SIgAD with CD in Italy. METHODS: Hospital medical records of 2098 patients
      consecutively diagnosed as having CD were reviewed. RESULTS: Of 2098 patients
      with CD, 54 (2.6%) had SIgAD, representing a 10-16-fold increase over that in the
      population in general. This increase was not influenced by age or geographical
      factors. Patients with SIgAD had a higher incidence of silent forms (7/54, 13%),
      recurrent infections (16/54, 29.6%), and atopic diseases (7/54, 13%) than those
      without. The association with autoimmune and malignant diseases and the outcome
      after eating a gluten free diet were similar in patients with or without SIgAD.
      In all patients with SIgAD, antibodies for IgA gliadin and endomysium were
      absent, but serum levels of IgG anti-gliadin antibodies were high in almost all
      of them (51/54). CONCLUSIONS: Serum IgA should be measured in order to be able to
      interpret negative results for IgA anti-gliadin antibodies and anti-endomysial
      antibodies in patients being screened for CD. Since some patients with CD and
      SIgAD may be negative for IgG anti-gliadin antibodies, an intestinal biopsy
      should be performed in all suspected cases.

PMID- 9577343
TI  - Focal reduction of villous blood flow in early indomethacin enteropathy: a
      dynamic vascular study in the rat.
AB  - BACKGROUND: Oral indomethacin causes villous shortening, microvascular damage,
      and distortion, which might induce mucosal ischaemia and necrosis. AIMS: In order
      to determine the early events in indomethacin induced jejunal injury we examined
      the temporal relations between morphological damage and changes in villous blood
      flow following indomethacin. METHODS: In anaesthetised rats, mid jejunal villi
      were exteriorised in a chamber and observed by fluorescence microscopy. Blood
      flow in surface capillaries was calculated from velocities and diameters.
      Indomethacin was applied by both luminal and intravenous routes for 90 minutes,
      after which the animal was perfusion fixed and the villi were processed for
      histological examination. Control animals received intravenous or luminal
      bicarbonate (1.25%). RESULTS: Blood flow slowed in individual villi at 20
      minutes, and progressed to complete stasis (in another group) by 45 minutes.
      Histological examination at 20 minutes revealed microvascular distortion, but no
      villous shortening; crypt depth:villous height ratios were 0.356 (0.02) in test
      and 0.386 (0.01) in surrounding villi (p > 0.05). At stasis, the villi under
      study showed epithelial clumping and were shortened: crypt depth:villous height
      ratios were 0.92 (0.2) in test and 0.42 (0.06) in surrounding villi (p < 0.02).
      Vehicle alone had no effect on either blood flow or histology. CONCLUSIONS: Focal
      slowing of villous blood flow and microvascular distortion precede villus
      shortening and epithelial disruption, and indicate that damage to surface
      microvasculature is an early event in indomethacin induced mucosal injury in this
      model.

PMID- 9577344
TI  - Mucosal subepithelial binding sites for the bacterial chemotactic peptide, formyl
      methionyl-leucyl-phenylalanine (FMLP).
AB  - BACKGROUND: The bacterial chemotactic peptide N-formyl-methionine-leucine
      phenylalanine (FMLP) is produced by enteric flora and is one of the factors
      implicated in contributing to inflammatory bowel disease. Expression of receptors
      for FMLP on human phagocytes (polymorphs and monocytes) is well established, but
      there is conflicting evidence regarding the potential expression of FMLP
      receptors on other cells within the mucosa, particularly the epithelial cells.
      AIMS: To map FMLP receptors within intestinal mucosa using several different
      experimental approaches. METHODS AND RESULTS: Radioligand binding assays with 'H
      FMLP' revealed no specific binding to primary cultured colonic enterocytes or to
      the cell line HT29, whereas neutrophils, as expected, exhibited specific binding
      with a Kd of 19 nM and approximately 2 x 10(4) receptors per cell. FITC labelled
      FMLP exhibited specific, displaceable binding on flow cytometry to neutrophils
      and monocytes but not to 10 gastrointestinal epithelial cell lines. Isolated
      lamina propria lymphocytes and peripheral blood lymphocytes exhibited no binding.
      To confirm the absence of receptors on epithelia, reverse transcription
      polymerase chain reaction for mRNA for the classic FMLP receptor was performed.
      While the presence of message was detected in activated peripheral blood
      phagocytes, it was not detected in epithelial cell lines. To exclude the
      possibility of FMLP binding to other receptors such as tachykinin receptors on
      epithelia, FITC labelled FMLP binding in tissue sections confirmed that the
      binding is subepithelial--that is, in the lamina propria. CONCLUSION: Receptors
      for FMLP are subepithelial and map to the lamina propria of the gastrointestinal
      mucosa.

PMID- 9577345
TI  - Leucocyte endothelial cell adhesion in indomethacin induced intestinal
      inflammation is correlated with faecal pH.
AB  - BACKGROUND: Recent studies indicate that faecal pH is acidified in patients with
      inflammatory bowel disease compared with healthy controls. In healthy volunteers,
      stool pH, faecal flora, and bile acid concentration could be affected by means of
      elemental diets. AIMS: To assess the role of variations of faecal pH on leucocyte
      endothelial cell adhesion in indomethacin induced long lasting ileitis in rats.
      METHODS: Indomethacin (7.5 mg/kg subcutaneously) was injected twice, 24 hours
      apart. Rats were either fed with the identical diet before and 10 days after the
      induction of inflammation until the experiment, or the diet was changed at the
      time of induction. Ten postcapillary mesenteric venules (30 microns diameter) per
      animal were observed using intravital microscopy. Macroscopic visible intestinal
      ulceration was scored and faecal pH of different sections of the small bowel was
      determined. RESULTS: Small intestinal faecal pH was 8.5 in controls and 8.0 in
      indomethacin treated animals. Indomethacin significantly changed microcirculatory
      parameters: there was a 2.3-fold increase in leucocyte adherence, a 3.2-fold
      increase in leucocyte emigration, and a 20% reduction in shear rate. Application
      of various diets or diet combinations resulted in variations in faecal pH ranging
      from 7.8 to 8.8 which were inversely correlated with macroscopic ulcerations (r =
      -0.67). Leucocyte adherence was attenuated with increased pH and augmented with
      decreased pH (r = -0.55). Venular wall shear rate was positively correlated with
      faecal pH (r = 0.48) while leucocyte emigration showed no correlation. Leucocyte
      rolling velocity was not significantly altered. Normalisation of faecal pH by
      different alkalising drugs induced a significant decrease in leucocyte adherence
      in standard fed, indomethacin treated rats. CONCLUSIONS: Faecal pH is lowered in
      the indomethacin model of long lasting ileitis in rats, which is similar to human
      inflammatory bowel disease. Alkalisation of faecal pH due to different diets or
      alkalising drugs reduces indomethacin induced leucocyte endothelial cell adhesion
      and macroscopic intestinal damage. These results may provide a rationale for the
      therapeutic effect of enteral diets in Crohn's disease.

PMID- 9577346
TI  - Peripheral arthropathies in inflammatory bowel disease: their articular
      distribution and natural history.
AB  - BACKGROUND: Peripheral arthropathy is a well-recognised complication of
      inflammatory bowel disease (IBD). Little is known of its natural history, but a
      variety of joint involvement has been described, from large joint pauciarticular
      arthropathy to a rheumatoid pattern polyarthropathy. AIMS: To classify the
      peripheral arthropathies according to pattern of articular involvement, and study
      their natural history and clinical associations. METHODS: The case notes of all
      patients attending the Oxford IBD clinic were reviewed, and information on
      general disease characteristics, extraintestinal features, and arthropathy
      extracted. This was confirmed by direct patient interview using questionnaires at
      routine follow up. Patients with recorded joint swelling or effusion were
      classified as type 1 (pauciarticular) if less than five joints were involved and
      type 2 (polyarticular) if five or more were involved. Patients without evidence
      of swelling were classified as arthralgia. RESULTS: In total, 976 patients with
      ulcerative colitis (UC) and 483 with Crohn's disease (CD) were reviewed. Type 1
      occurred in 3.6% of patients with UC (83% acute and self-limiting) and in 6.0% of
      those with CD (79% self-limiting); 83% and 76%, respectively, were associated
      with relapsing IBD. Type 2 occurred in 2.5% of patients with UC and 4.0% of those
      with CD; 87% and 89%, respectively, caused persistent symptoms whereas only 29%
      and 42%, respectively, were associated with relapsing IBD. CONCLUSION:
      Enteropathic peripheral arthropathy without axial involvement can be subdivided
      into a pauciarticular, large joint arthropathy, and a bilateral symmetrical
      polyarthropathy, each being distinguished by its articular distribution and
      natural history.

PMID- 9577347
TI  - Crohn's-like reaction in diverticular disease.
AB  - BACKGROUND: Diverticulitis and Crohn's disease affecting the colon occur at
      similar sites in older individuals, and in combination are said to carry a worse
      prognosis than either disease in isolation. It is possible that diverticulitis
      may initiate inflammatory changes which resemble Crohn's disease histologically,
      but do not carry the clinical implications of chronic inflammatory bowel disease.
      AIMS: To evaluate histological features and clinical outcome in individuals
      initially diagnosed histologically as having both Crohn's colitis and
      diverticulitis. PATIENTS: Eleven consecutive individuals having a colonic
      resection showing histological features of both Crohn's disease and
      diverticulitis. METHODS: Retrospective review of histological specimens, case
      notes, and discharge letters. RESULTS: In nine patients, the Crohn's-like
      reaction was confined to the segment bearing diverticula. They had no clinical
      evidence of Crohn's disease. CONCLUSION: A Crohn's-like inflammatory response can
      be a localised reaction to diverticulitis and does not necessarily indicate
      chronic inflammatory bowel disease.

PMID- 9577348
TI  - Gut barrier function in malnourished patients.
AB  - BACKGROUND: The integrity of the gastrointestinal mucosa is a key element in
      preventing systemic absorption of enteric toxins and bacteria. In the critically
      ill, breakdown of gut barrier function may fuel sepsis. Malnourished patients
      have an increased risk of postoperative sepsis; however, the effects of
      malnutrition on intestinal barrier function in man are unknown. AIMS: To quantify
      intestinal barrier function, endotoxin exposure, and the acute phase cytokine
      response in malnourished patients. PATIENTS: Malnourished and well nourished
      hospitalised patients. METHODS: Gastrointestinal permeability was measured in
      malnourished patients and well nourished controls using the lactulose:mannitol
      test. Endoscopic biopsy specimens were stained and morphological and
      immunohistochemical features graded. The polymerase chain reaction was used to
      determine mucosal cytokine expression. The immunoglobulin G antibody response to
      endotoxin and serum interleukin 6 were measured by enzyme linked immunosorbent
      assay. RESULTS: There was a significant increase in intestinal permeability in
      the malnourished patients in association with phenotypic and molecular evidence
      of activation of lamina propria mononuclear cells and enterocytes, and a
      heightened acute phase response. CONCLUSIONS: Intestinal barrier function is
      significantly compromised in malnourished patients, but the clinical significance
      is unclear.

PMID- 9577350
TI  - Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder
      motility.
AB  - BACKGROUND: Nitric oxide is a major neurotransmitter in non-adrenergic, non
      cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human
      gall bladder muscle in vitro; the role of nitric oxide in human gall bladder
      emptying however is undefined. AIMS: To study the effect of glyceryl trinitrate,
      a nitric oxide donor, on gall bladder emptying in healthy subjects using a
      randomised, double blind, cross-over, placebo controlled design. METHODS:
      Ultrasonographic gall bladder volume was measured in the fasting state in eight
      healthy volunteers after randomised administration of either glyceryl trinitrate
      1200 micrograms buccal spray or placebo spray. On two further occasions, after
      randomised administration of either glyceryl trinitrate 1200 micrograms buccal
      spray or placebo spray, gall bladder volumes were also measured after a liquid
      test meal. RESULTS: Glyceryl trinitrate significantly increased fasting gall
      bladder volume to a mean of 114% (SEM 5%) of pretreatment volume (p = 0.039).
      Glyceryl trinitrate also significantly impaired gall bladder emptying between
      five and 40 minutes postprandially. Gall bladder ejection fraction was also
      reduced after glyceryl trinitrate compared with placebo (43 (6.9)% versus 68.4
      (6.5)%, p = 0.016). CONCLUSIONS: This study shows that glyceryl trinitrate
      produces gall bladder dilatation in the fasting state and reduces postprandial
      gall bladder emptying, suggesting that nitric oxide mechanisms may be operative
      in the human gall bladder in vivo.

PMID- 9577349
TI  - Expression of arylamine N-acetyltransferase in human intestine.
AB  - BACKGROUND: Arylamine N-acetyltransferases in humans (NAT1 and NAT2) catalyse the
      acetylation of arylamines including food derived heterocyclic arylamine
      carcinogens. Other substrates include the sulphonamide 5-aminosalicylic acid (5
      ASA), which is an NAT1 specific substrate; N-acetylation of 5-ASA is a major
      route of metabolism. NAT1 and NAT2 are both polymorphic. AIMS: To investigate NAT
      expression in apparently healthy human intestines in order to understand the
      possible role of NAT in colorectal cancer and in the therapeutic response to 5
      ASA. METHODS: The intestines of four organ donors were divided into eight
      sections. DNA was prepared for genotyping NAT1 and NAT2 and enzymic activities of
      NAT1 and NAT2 were determined in cytosols prepared from each section. Tissue was
      fixed for immunohistochemistry with specific NAT antibodies. Western blotting was
      carried out on all samples of cytosol and on homogenates of separated muscle and
      villi after microdissection. RESULTS: NAT1 activity of all cytosols was greater
      than NAT2 activity. NAT1 and NAT2 activities correlated with the genotypes of
      NAT1 and NAT2 and with the levels of NAT1 staining determined by western
      blotting. The ratio of NAT1:NAT2 activities showed interindividual variations
      from 2 to 70. NAT1 antigenic activity was greater in villi than in muscle. NAT1
      was detected along the length of the villi in the small intestine. In colon
      samples there was less NAT1 at the base of the crypts with intense staining at
      the tips. CONCLUSIONS: The interindividual variation in NAT1 and NAT2 in the
      colon could affect how individuals respond to exposure to specific NAT substrates
      including carcinogens and 5-ASA.

PMID- 9577351
TI  - Functional gastrointestinal disorders: psychological, social, and somatic
      features.
AB  - BACKGROUND: Psychological, social, and extraintestinal (somatic) disturbances are
      prominent features of functional gastrointestinal disorders (FGID); little
      attention, however, has been given to differences in the nature of these
      disturbances in the various FGID subgroups. AIMS: (1) To determine whether
      psychological, social, and extraintestinal factors are associated with specific
      FGID, and/or with the overall severity and extent of FGID disturbance (the number
      of coexistent FGID subgroups present in any individual); and (2) to determine
      whether chronic social stressors link gastrointestinal, extraintestinal, and
      emotional symptomatologies in FGID. PATIENTS: One hundred and eighty eight
      outpatients, fulfilling standard criteria for one or more functional
      gastroduodenal or functional bowel disorders. METHODS: Utilising detailed and
      objective interview and questionnaire methods, detailed gastrointestinal,
      extraintestinal, psychological, and social data were collected. RESULTS: Chronic
      stressors and extraintestinal and emotional symptomatologies were prominent
      features of functional dyspepsia (FD) and irritable bowel syndrome (IBS) alone.
      These particular features were, however, highly specific for particular FD and/or
      IBS subgroups. The chronic threat component of social stressors predicted the
      nature and extent of multisystem (gastrointestinal, extraintestinal, and
      emotional) symptomatology. CONCLUSIONS: Notable differences between the various
      FGID subgroups support the symptom based classification of FGID. Chronic stressor
      provoked psychological and extraintestinal disturbance is most specific for the
      FD-IBS group of syndromes.

PMID- 9577352
TI  - Diagnostic yield of push-type enteroscopy in relation to indication.
AB  - BACKGROUND: Push-type enteroscopy, a recent method for investigating the small
      intestine, is currently undergoing assessment. Its diagnostic yield varies in the
      studies reported to date. AIM: To assess the diagnostic value of push-type
      enteroscopy according to indication. PATIENTS AND METHODS: From January 1994 to
      September 1995, 152 consecutive patients (mean age 34 years) underwent push-type
      enteroscopy (jejunoscopy, n = 93; retrograde ileoscopy, n = 17; and double way
      enteroscopy, n = 42). The indications were: unexplained iron deficiency anaemia
      or macroscopic gastrointestinal bleeding (n = 76), radiological abnormalities of
      the small intestine (n = 23), chronic diarrhoea and/or malabsorption syndrome (n
      = 18), abdominal pain (n = 12), and miscellaneous (n = 23). All patients had
      undergone previous negative aetiological investigations. RESULTS: The jejunum and
      ileum were explored through 120 cm (30-160 cm) and 60 cm (20-120 cm). Digestive
      bleeding: lesions of the small bowel were found in 6% of the patients with
      isolated iron deficiency anaemia and 20% of patients with patent digestive
      haemorrhage. Radiological abnormalities of the small intestine: push-type
      enteroscopy provided a diagnosis or modified the interpretation of radiological
      findings in 18/23 cases (78%). Chronic diarrhoea and/or malabsorption: push-type
      enteroscopy yielded explanatory findings in four cases (22%). Abdominal pain:
      push-type enteroscopy provided no diagnosis. CONCLUSION: In this series, push
      type enteroscopy was of particular value in investigating patients with
      radiological abnormalities of the small intestine. It was of some value in the
      exploration of patent digestive haemorrhage or chronic diarrhoea, but not of
      abdominal pain. Its value was limited in the exploration of iron deficiency
      anaemia.

PMID- 9577353
TI  - Cytochrome P4502E1 is present in rat pancreas and is induced by chronic ethanol
      administration.
AB  - BACKGROUND: The mechanisms responsible for the initiation of alcoholic
      pancreatitis remain elusive. However, there is an increasing body of evidence
      that reactive oxygen species play a role in both acute and chronic pancreatitis.
      In the liver, cytochrome P4502E1 (CYP2E1, the inducible ethanol metabolising
      enzyme) is one of the proposed pathways by which ethanol induces oxidative
      stress. AIMS: To determine whether CYP2E1 is present in the pancreas and, if so,
      whether it is inducible by chronic ethanol feeding. METHODS: Eighteen male
      Sprague-Dawley rats were pair fed liquid diets with or without ethanol as 36% of
      energy for four weeks. CYP2E1 levels were determined by western blotting of
      microsomal protein from both pancreas and liver. Messenger RNA (mRNA) levels for
      CYP2E1 were quantified using dot blots of total pancreatic RNA. RESULTS: CYP2E1
      was found in the pancreas. Furthermore, the amount of CYP2E1 was greater in the
      pancreas of rats fed ethanol compared with controls (mean increase over controls
      5.1-fold, 95% confidence intervals 2.4 to 7.7, p < 0.02). In the liver, induction
      by ethanol of CYP2E1 was similar (mean increase over controls 7.9-fold, 95%
      confidence intervals 5.2 to 10.6, p < 0.005). Pancreatic mRNA levels for CYP2E1
      were similar in ethanol fed and control rats. CONCLUSIONS: CYP2E1 is present in
      the rat pancreas and is inducible by chronic ethanol administration. Induction of
      pancreatic CYP2E1 is not regulated at the mRNA level. The metabolism of ethanol
      via CYP2E1 may contribute to oxidative stress in the pancreas during chronic
      ethanol consumption.

PMID- 9577354
TI  - Compared with parenteral nutrition, enteral feeding attenuates the acute phase
      response and improves disease severity in acute pancreatitis.
AB  - BACKGROUND: In patients with major trauma and burns, total enteral nutrition
      (TEN) significantly decreases the acute phase response and incidence of septic
      complications when compared with total parenteral nutrition (TPN). Poor outcome
      in acute pancreatitis is associated with a high incidence of systemic
      inflammatory response syndrome (SIRS) and sepsis. AIMS: To determine whether TEN
      can attenuate the acute phase response and improve clinical disease severity in
      patients with acute pancreatitis. METHODS: Glasgow score, Apache II, computed
      tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin
      antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on
      admission in 34 patients with acute pancreatitis. Patients were stratified
      according to disease severity and randomised to receive either TPN or TEN for
      seven days and then re-evaluated. RESULTS: SIRS, sepsis, organ failure, and ITU
      stay, were globally improved in the enterally fed patients. The acute phase
      response and disease severity scores were significantly improved following
      enteral nutrition (CRP: 156 (117-222) to 84 (50-141), p < 0.005; APACHE II scores
      8 (6-10) to 6 (4-8), p < 0.0001) without change in the CT scan scores. In
      parenterally fed patients these parameters did not change but there was an
      increase in EndoCAb antibody levels and a fall in TAC. Enterally fed patients
      showed no change in the level of EndoCAb antibodies and an increase in TAC.
      CONCLUSION: TEN moderates the acute phase response, and improves disease severity
      and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced
      systemic exposure to endotoxin and reduced oxidant stress also occurred in the
      TEN group. Enteral feeding modulates the inflammatory and sepsis response in
      acute pancreatitis and is clinically beneficial.

PMID- 9577355
TI  - Secretory immunoglobulin A in pancreatic juice and pancreatic tissue of patients
      with chronic pancreatitis.
AB  - BACKGROUND: The predominance of secretory IgA (S-IgA) in intestinal secretions
      compared with blood is well established, but concentrations of this protein in
      pancreatic juice and its origin, especially in chronic pancreatitis, are unknown.
      AIMS: To investigate the role of S-IgA in chronic pancreatitis. PATIENTS: Twenty
      one patients with chronic pancreatitis (group I), three patients with proven
      malignancies (group II), and 12 patients without pancreatic disease (group III).
      METHODS: Pure human pancreatic juice was collected endoscopically in four
      fractions after consecutive stimulation with secretin and cholecystokinin (CCK).
      Samples were analysed for S-IgA, protein, trypsinogen, and proteolytic activity.
      RESULTS: The S-IgA level was significant increased in fraction 1 of pancreatic
      juice of group I (1210 (1411) ng/ml) compared with controls (33 (70) ng/ml).
      Protein concentrations and trypsinogen content were lower in group I than in the
      other groups. Proteolytic activity could be observed in 53% of all 133 pancreatic
      juice samples, but in 87% of fraction 1. In pancreatic tissue of three patients
      with chronic pancreatitis both IgA and secretory component were detected by
      immunohistology. Expression of the secretory component by human pancreatic
      epithelial cells was increased in patients with chronic pancreatitis compared
      with normal controls. The concentration of S-IgA in pancreatic juice did not
      correlate with the serum S-IgA level. In contrast, serum levels of S-IgA were
      decreased in patients with chronic pancreatitis. CONCLUSION: There are high
      levels of S-IgA in human pancreatic juice following chronic inflammation and a
      protective role is suggested for this immunoglobulin.

PMID- 9577357
TI  - Autoimmune hepatitis in the elderly.

PMID- 9577356
TI  - Treatment of hepatocellular carcinoma with octreotide: a randomised controlled
      study.
AB  - BACKGROUND: Standard treatment of inoperable hepatocellular carcinoma has not
      been established. Somatostatin has been shown to possess antimitotic activity
      against a variety of non-endocrine tumours. AIMS: To assess the presence of
      somatostatin receptors in human liver and to treat advanced hepatocellular
      carcinoma with the somatostatin analogue, octreotide. METHODS: Somatostatin
      receptors were measured in liver tissue homogenates from patients with acute and
      chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Fifty eight patients
      with advanced hepatocellular carcinoma were randomised to receive either
      subcutaneous octreotide 250 micrograms twice daily, or no treatment. Groups were
      comparable with respect to age, sex, Okuda classification, presence of cirrhosis,
      and liver biochemistry and virology. RESULTS: Various amounts of somatostatin
      receptors were identified in liver tissue of all patients including those with
      hepatocellular carcinoma. Treated patients had an increased median survival (13
      months versus four months, p = 0.002, log rank test) and an increased cumulative
      survival rate at six and 12 months (75% versus 37%, and 56% versus 13%
      respectively). Octreotide administration significantly reduced alpha fetoprotein
      levels at six months. When a multivariable Cox's proportional hazards model was
      fitted, variables associated with increased survival were: treatment
      administration, absence of cirrhosis, increased serum albumin, and small tumours.
      Treated patients clearly had a lower hazard (0.383) in the multivariate analysis.
      CONCLUSIONS: Octreotide administration significantly improves survival and is a
      valuable alternative in the treatment of inoperable hepatocellular carcinoma.

PMID- 9577358
TI  - Consideration of histopathological subtypes and biopsy techniques in Barrett's
      oesophagus surveillance programmes.

PMID- 9577359
TI  - Electrical spinal cord stimulation for painful peripheral neuropathy secondary to
      coeliac disease.

PMID- 9577360
TI  - Research misconduct and redundant publication.

PMID- 9577361
TI  - Diagnosis of polycythaemia.

PMID- 9577362
TI  - Early diagnosis of myocardial infarction: why measure cardiac enzymes?

PMID- 9577363
TI  - Pathological changes in prostate lesions after androgen manipulation.
AB  - The number of newly diagnosed cases of prostate cancer has doubled in the past
      four years because of the aging of the population coupled with growing awareness
      of the importance of early detection. The issues of clinical understaging and
      resection limit positivity have led to the development of novel management
      practices, including neoadjuvant hormonal treatment, which aims to downstage the
      primary tumour and decrease the positive margin rate before definitive localised
      treatment (radical prostatectomy or definitive radiation treatment
      (neoadjuvant)). There is conflicting evidence regarding pathological downstaging,
      with some studies suggesting benefit and others no benefit of androgen
      manipulation before radical prostatectomy. The problem might be related to
      incomplete sampling of the prostates and difficulties associated with the
      pathological interpretation of morphological changes. The least controversial
      aspect of neoadjuvant treatment is its impact on surgical margins. Most series
      have shown that neoadjuvant treatment in clinical T2 tumours is associated with a
      20-25% decrease in positive margins in radical prostatectomy specimens. In
      patients with clinical T3 tumours, the effects of neoadjuvant treatment on
      positive margins are less clear. Even if some early significant advantages can be
      observed following hormonal treatment this may not alter the metastatic spread
      and overall survival rate. Only long term follow up studies evaluating biological
      and clinical failures, time to progression, and survival will allow definitive
      conclusions from this approach.

PMID- 9577364
TI  - Neural cell adhesion molecule L1 in gliomas: correlation with TGF-beta and p53.
AB  - AIMS: To assess immunohistochemically whether the neural cell adhesion molecule
      L1, which is a member of the immunoglobulin superfamily and has been shown
      recently to be a stimulating factor for glioma migration, is expressed in glioma
      tissues, and to investigate factors that can regulate this expression. METHODS:
      Twenty seven glioma tissue specimens including 13 glioblastomas, seven anaplastic
      astrocytomas, and seven astrocytomas were examined. Immunohistochemical analyses
      of L1, p53, and transforming growth cell factor beta (TGF-beta) were performed on
      each tumour using both polyclonal and monoclonal antibodies. RESULTS: Nine (33%)
      specimens (six glioblastomas and three anaplastic astrocytomas) had L1 positive
      immunostaining. p53 positive staining was detected in 10 (43%) of 23 glioma
      specimens (seven glioblastomas and three anaplastic astrocytomas). TGF-beta
      positive immunostaining was observed in 12 (52%) of the 23 glioma specimens (six
      glioblastomas, four anaplastic astrocytomas, and two astrocytomas). There was a
      statistical correlation between both p53 and L1 expression and TGF-beta and L1
      expression. No such correlation was found between p53 and TGF-beta expression.
      CONCLUSIONS: These results suggest that mutation of the p53 gene or expression of
      TGF-beta may upregulate the expression of the L1 gene, thus resulting in high
      grade migration of glioma cells.

PMID- 9577365
TI  - Apparent deficiency of mucosal vascular collagen type IV associated with
      angiodysplasia of the colon.
AB  - AIMS: To investigate the presence and distribution of vascular collagen type IV
      in colonic tissue in cases of angiodysplasia and age and sex matched controls.
      METHODS: Sections of colon from seven cases of colonic angiodysplasia and eight
      age and sex matched controls were examined for the presence of collagen type IV
      in vessels of the mucosa and submucosa. Immunohistochemical staining was
      performed on paraffin wax embedded sections, and the degree of vascular staining
      for each marker compared between mucosa and submucosa and between cases and
      controls. Staining for endothelial markers P-selection and factor VIII was used
      to control for non-specific differences in immunostaining. RESULTS: In both the
      angiodysplastic tissues and approximately half the control tissues, staining for
      collagen type IV was considerably weaker in vessels in the mucosa than in the
      submucosa. In angiodysplasia, ectatic vessels in the mucosa appeared to contain
      less collagen type IV than similarly sized vessels in the submucosa, and
      perforating vessels appeared in many cases to lose staining at the level of the
      muscularis mucosae. No differences were found in staining intensity for the
      control endothelial markers between cases and controls. CONCLUSIONS: The apparent
      relative deficiency of collagen type IV in the mucosal vessels in angiodysplasia
      may be related to their susceptibility to ectasia and haemorrhage. The finding of
      a similar deficiency in half of the control cases may reflect a population at
      risk of this relatively common condition.

PMID- 9577366
TI  - An inexpensive and reliable new haemoglobin colour scale for assessing anaemia.
AB  - AIM: To describe a new inexpensive method (the WHO Colour Scale) for estimating
      haemoglobin concentration from a drop of blood by means of a colour scale, and to
      compare its reliability with a standard laboratory method of measuring
      haemoglobin, and its clinical usefulness in field trials. METHODS: The new colour
      scale method was used to measure haemoglobin concentration in 1213 random venous
      blood samples from routine work in four laboratories (one each in the UK, South
      Africa, Thailand, and Switzerland). Limited field trials of the method for
      assessing clinical usefulness were done in a rural hospital (in South Africa)
      staffed by nurses, at two blood donor sessions (one each in South Africa and
      Thailand), and by nonlaboratory personnel in malaria clinics (in Thailand),
      following training and a short practice session. RESULTS: In the laboratory based
      comparability study the presence of anaemia was reliably detected using the new
      method with 91% sensitivity and 86% specificity. Clinically relevant levels of
      anaemia (mild to moderate, pronounced, and severe) were graded and serious
      anaemia (< 8 g/dl) was identified with an efficiency of 89%. The clinical trials
      showed the ease and reliability with which the colour scale could be used by non
      laboratory persons after brief training. The blood donor trials showed it to be
      at least as reliable as the copper sulphate method with the advantage of being
      more convenient. CONCLUSIONS: The preliminary studies have shown that the WHO
      Colour Scale is a reliable screening method for detecting anaemia, especially for
      diagnosing serious anaemia. Following a brief training session health workers
      found it simple to use and, at a cost of about 1/10th that for traditional
      photometric analysis, it should be of value in "countries in need" for primary
      health centres, obstetrical management, paediatric clinics, tropical disease
      control programmes, blood transfusion donor selection, as well as for industrial
      health checks and epidemiological studies.

PMID- 9577367
TI  - Endometrial carcinoma: immunohistochemically detected proliferation index is a
      prognosticator of long-term outcome.
AB  - AIM: To test which immunohistochemically detected tumour parameters are
      predictive of outcome in endometrial carcinoma. METHODS: A retrospective study of
      300 patients diagnosed with endometrial carcinoma between 1980 and 1985, ensuring
      a follow up of at least 10 years. Paraffin wax embedded tissues from 236 patients
      with endometrial carcinoma were evaluated in terms of histological tumour type
      and grade, stage of disease, and certain immunohistochemical biological
      parameters. These parameters included the expression of oestrogen and
      progesterone receptors, the expression of p53 protein, the expression of the c
      erbB-2 oncoprotein, and the expression of protease cathepsin D, together with the
      rate of cell proliferation. RESULTS: Using univariate analysis, the following
      parameters correlated significantly with adjusted survival: histological type (p
      = 0.025), grade (p = 0.00003), FIGO stage (p < 0.00001), proliferation rate (p =
      0.00002), oestrogen receptor expression (p = 0.007), progesterone receptor
      expression (p = 0.0092), and p53 expression (p = 0.00028). These parameters also
      correlated significantly with both disease free and overall survival. There was a
      weak correlation of cathepsin D expression with survival, but no correlation of c
      erb B-2 expression with survival. Using multivariate analysis, only FIGO stage (p
      = 0.0021), histological grade (p = 0.005), and proliferation rate (p = 0.0007)
      remained statistically significant prognosticators of adjusted survival as well
      as of disease free and overall survival. CONCLUSIONS: In addition to conventional
      histological parameters, the immunohistochemical determination of proliferative
      activity could contribute to the identification of a high risk subgroup of
      endometrial carcinomas. The other parameters tested were not of significant
      additional predictive value.

PMID- 9577368
TI  - Evidence of effectiveness of clinical audit in improving histopathology reporting
      standards of mastectomy specimens.
AB  - AIM: To assess the effectiveness of clinical audit in improving standards in
      histopathological reporting of mastectomy specimens. METHODS: Reports on
      mastectomy specimens containing tumour issued by non-specialist histopathologists
      in 1990, 1992, 1994, and 1996 were scored for their information content. There
      were 10 reports evaluated from each year. Before 1990 no reporting guidelines had
      been formulated within the department. The audits in 1992 and 1994 were performed
      after agreed written guidelines (including the establishment of six essential
      pieces of information), and in 1996 the specimens were reported using a proforma.
      RESULTS: There was a significant increase in information after the introduction
      of written guidelines but there was a reduction in information over time. In 1990
      none of the 10 reports included all six pieces of mandatory information; in 1992
      four of the reports contained all mandatory information; in 1994 only one report
      contained all mandatory information. The introduction of a proforma for reporting
      resulted in further significant improvement with all 10 reports in 1996
      containing all mandatory information. CONCLUSIONS: Successive rounds of audit
      increases the standard of reporting in histopathology. There is a need for
      continuing monitoring of standards as these may deteriorate over time. Reporting
      complex specimens on a proforma has a significant beneficial effect on
      information content.

PMID- 9577369
TI  - Comparison of in situ methods to assess DNA cleavage in apoptotic cells in
      patients with breast cancer.
AB  - BACKGROUND: Apoptosis has a role in many cellular processes including
      development, normal tissue homeostasis, and malignancy. This aspect of research
      is relatively new with distinct methods of analysing disparate biochemical and
      genetic events to measure apoptotic cells. The use of biotinylated nucleotides to
      identify DNA strand breaks is a commonly reported method of estimating cells
      numbers undergoing apoptosis; however, investigators report inconsistent results
      for a variety of reasons. AIMS AND METHOD: To compare two in situ techniques of
      measuring apoptosis: in situ nick translation (ISNT) and TdT mediated dUTP-biotin
      nick end labelling (TUNEL); and to assess DNA cleavage in 20 paired paraffin wax
      embedded breast cancer tissues from patients; one group who had received no prior
      treatment and one group who had received chemohormonal treatment. RESULTS AND
      CONCLUSIONS: Apoptotic scores obtained from paraffin wax embedded human breast
      cancer after using ISNT and TUNEL methods were not significantly different (p =
      0.11). A strong correlation between scores obtained from the two techniques was
      found (r = 0.758, p < 0.0001). Optimisation of both techniques is crucial to
      ensure maximal assay performance in breast cancer tissue.

PMID- 9577370
TI  - DNA-EIA to detect high and low risk HPV genotypes in cervical lesions with E6/E7
      primer mediated multiplex PCR.
AB  - BACKGROUND: Oncogenicity of human papillomavirus (HPV) DNA in premalignant and
      malignant uterine cervical diseases is mainly induced by E6/E7 open reading frame
      (ORF). The presence of an oncogenic HPV DNA may be a diagnostic marker for the
      detection of cytologically negative smears. AIMS: To evaluate an original
      polymerase chain reaction enzyme immunoassay (PCR-EIA) for the detection and
      typing of oncogenic and non-oncogenic HPV types. METHODS: The test was an
      original multiplex labelled PCR-EIA for the detection and typing of oncogenic and
      non-oncogenic HPV using three consensus sequence primers within the oncogenic
      E6/E7 ORF. One primer was dinitrophenyl (DNP) labelled and the DNP labelled
      amplimers could be further hybridised with specific biotinylated oligoprobes
      mixed in only two cocktails: oncogenic (16, 18, 31, 33, 35, 52, and 58) and non
      oncogenic (6 and 11) HPV types in only two wells; then biotinylated oligoprobes
      were deposited in streptavidin-coated microplates. The PCR-EIA was validated on
      HPV plasmids (types 6, 11, 16, 18, 31, 35, 52, and 58) and used to evaluate
      cervical scrapes from 181 patients (median age 32 years) at high risk for
      cervical cancer. RESULTS: HPV were detected in the cervical scrapes of 88 of 181
      patients (48.6%); nine with non-oncogenic HPV (5.0%) and 79 with oncogenic HPV
      (43.6%) including 29 coinfections with oncogenic and non-oncogenic HPV. The
      number of oncogenic HPV infections increased with the presence of high grade
      lesions: 95.8% of the cervical scrapes from patients with high grade lesions
      contained oncogenic HPV compared with 32.1% of the specimens from patients
      without any lesions detectable by colposcopy and/or by cytological examination of
      the cervical smears. Moreover, 60% of cervical scrapes exhibiting low grade
      lesions contained oncogenic HPV. CONCLUSIONS: This test is simple, specific,
      sensitive, safe, fast, reproducible, and easy to use in routine practice. Thus,
      it is possible to detect simultaneously on a simple cervical scrape, two kinds of
      HPV--oncogenic and non-oncogenic--in just two microplate wells with non-isotopic
      oligoprobes.

PMID- 9577371
TI  - Decreased type V collagen expression in human decidual tissues of spontaneous
      abortion during early pregnancy.
AB  - AIM: To provide some insight into the aetiology of spontaneous abortion, the
      contents of type V collagen was investigated in human decidual tissues in
      spontaneous abortion and normal pregnancy. METHODS: Collagens were extracted from
      decidual tissues in spontaneous abortion (n = 19) and normal pregnancy (n = 25).
      The different types of collagen alpha chains were separated by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), stained with Coomassie
      brilliant blue, and measured by densitometry. The relative amounts of the alpha 1
      (III) and alpha 1 (V) chains were calculated by dividing the band intensities of
      the alpha 1 (III) and alpha 1 (V) chains by that of the alpha 1 (I) chain.
      RESULTS: The ratio of the alpha 1 (V) chain to that of the alpha 1 (I) chain in
      decidual tissues in spontaneous abortion was significantly lower than that found
      in normal pregnancy (p < 0.05). CONCLUSIONS: These results suggest that type V
      collagen might play an important role in the maintenance of pregnancy and that
      decreased expression of this collagen could be associated with spontaneous
      abortion.

PMID- 9577373
TI  - CD44 expression in normal adrenal tissue and adrenal tumours.
AB  - BACKGROUND: CD44 is a cell surface glycoprotein found on many normal cells,
      mainly lymphoid and epithelial. Normal cells usually express standard CD44 (CD44
      S), whereas malignant tumours may express CD44 variant isoforms (CD44-V). CD44
      expression has been described for neural crest derivatives. Characterisation of
      differences in CD44 expression may help in the diagnosis and differentiation of
      distinct adrenal tumours. AIMS: To examine CD44 expression in different layers of
      cortical cortex, in adrenal medulla, and in adrenal tumours. METHODS: CD44-S and
      CD44-V6 expression were studied in 12 cases of adrenal cortical adenoma, 3 of
      adrenal cortical carcinoma, 10 of pheochromocytoma, and 4 normal adrenal glands.
      RESULTS: CD44-V6 staining showed cytoplasmic expression in normal adrenal cortex
      and in cortical adenomas and carcinomas. Pheochromocytomas also showed CD44-V6
      expression but in 5 of the 10 cases it was sparse, focal, and sometimes
      perinuclear. Strong membranous staining for CD44-S was observed in normal adrenal
      medulla. Analysis of CD44-S expression revealed differences between cortical
      adrenal tumours and pheochromocytomas. Ten of 12 cortical adenomas and 2 of 3
      cortical carcinoma cells showed weak to moderate cytoplasmic staining, but all
      cases of pheochromocytoma had strong membranous staining. CONCLUSIONS: Membranous
      CD44-S staining may help to distinguish pheochromocytoma from adrenal cortical
      adenoma.

PMID- 9577375
TI  - Identification of multiresistant Staphylococcus epidermidis in neonates of a
      secondary care hospital using pulsed field gel electrophoresis and quantitative
      antibiogram typing.
AB  - AIMS: To determine the diversity of types of Staphylococcus epidermidis in a
      neonatal care unit of a secondary care hospital in the Netherlands. METHODS: In a
      prospective study, specimens from nose, ear, axilla, umbilicus, and groin were
      taken from patients twice a week during a period of up to two weeks. All isolates
      were typed by both pulsed field gel electrophoresis (PFGE) and antibiogram
      analysis. RESULTS: Fifty three S epidermidis isolates from 15 of 24 patients were
      obtained in one to four surveys. Fourteen isolates from six patients had a common
      PFGE pattern and were of one multiresistant antibiogram type. The remaining 39
      isolates were allocated to 24 sporadic PFGE types and were more susceptible to
      antibiotics. Colonisation with the multiresistant strain correlated with a long
      period of stay and with the use of specific antibiotics. The multiresistant
      isolates were related closely to isolates of S epidermidis found in a recent
      study in a teaching hospital in the vicinity of the secondary care hospital.
      CONCLUSION: Repeated sampling and the use of two typing methods allowed the
      identification of two closely related multiresistant S epidermidis strains in two
      hospitals in the same area.

PMID- 9577374
TI  - Clinical and histological associations of cagA and vacA genotypes in Helicobacter
      pylori gastritis.
AB  - AIMS: To determine the relation among the cytotoxin associated gene (cagA) and
      vacuolating cytotoxin gene (vacA) status of Helicobacter pylori isolates, the
      associated clinical diseases, and the severity and pattern of chronic gastritis.
      METHODS: Helicobacter pylori was cultured from gastric biopsies obtained from
      dyspeptic patients. DNA was extracted from the isolates and the cagA and vacA
      status determined by the polymerase chain reaction (PCR). The prevalence of the
      different cagA and vacA genotypes in three clinical groups, duodenal ulcer,
      gastric ulcer, and non-ulcer dyspepsia was compared. The histological features in
      sections from two antral and two corpus biopsies were graded by one blinded
      observer. The grades were compared with age and sex matched groups with different
      cagA and vacA genotypes, and with duodenal ulcers, or non-ulcer dyspepsia.
      RESULTS: Isolates from 161 patients were included. One hundred and nine (68%)
      harboured a cagA+ strain and 143 (89%) harboured a vacA s1 strain. The prevalence
      of cagA+ strains in duodenal ulcer patients (94%) was highly significantly
      greater than in those with non-ulcer dyspepsia (56%). However, of the patients
      infected with a cagA+ strain, almost equal numbers had non-ulcer dyspepsia or
      peptic ulceration. Chronic inflammation, polymorph activity, surface epithelial
      degeneration, atrophy, and intestinal metaplasia were all significantly more
      severe in the cagA+ than in the cagA- group, whereas only corpus epithelial
      degeneration was significantly more severe in the vacA s1 group compared with the
      vacA s2 group. Patients infected with cagA+ strains were almost four times more
      likely to have antral intestinal metaplasia than cagA- patients. An antral
      predominant gastritis was present in duodenal ulcer patients compared with
      matched non-ulcer dyspepsia patients, but this was not attributable to cagA or
      vacA status. CONCLUSIONS: Helicobacter pylori strains showing cagA positively and
      the vacA s1 genotype are associated with more severe gastritis but these
      virulence factors do not appear to determine the overall pattern. The pattern is
      closely linked to clinical disease. Therefore, it is likely that the nature of
      the disease complicating chronic infection is determined by host and
      environmental factors, while bacterial factors determine the magnitude of the
      risk of developing such disease.

PMID- 9577372
TI  - Expression of proliferation associated antigens and detection of numerical
      chromosome aberrations in primary human liver tumours: relevance to tumour
      characteristics and prognosis.
AB  - AIMS: To assess cell proliferation and the presence of numerical chromosome
      aberrations involving chromosomes 1 and 8 in benign and malignant liver tumours.
      METHODS: Cell proliferation was studied immunohistochemically in paraffin wax
      embedded material from 62 primary liver tumours (20 hepatocellular carcinomas, 16
      cholangiocellular carcinomas, 15 liver cell adenomas, 11 focal nodular
      hyperplasias), and the results were compared with histological characteristics
      and clinical data. Copy numbers of chromosomes 1 and 8 were assessed by
      interphase fluorescence in situ hybridisation (FISH) with satellite probes in
      fresh tumour material. RESULTS: The expression of proliferation associated
      antigen Ki67, using the monoclonal antibody MIB-1, and proliferating cell nuclear
      antigen (PCNA), using the antibody PC10, was found to be significantly higher in
      malignant versus benign liver tumours. Neither Ki67 nor PCNA expression were
      independent prognostic parameters. However, there was a tendency for a worse
      outcome (survival < 12 months) for patients with a high MIB-1 labelling index (>
      20%) compared with patients having the same tumour stage and a low MIB-1 index.
      Aneusomy for chromosomes 1 and 8 was demonstrated by FISH in malignant tumours
      (six of seven hepatocellular carcinomas, four of five cholangiocellular
      carcinomas) but not in benign tumours (none of nine) or non-neoplastic liver
      (none of nine). CONCLUSION: Both the determination of the proliferating cell
      fraction and FISH analysis are useful for distinguishing hepatocellular carcinoma
      from liver cell adenoma or focal nodular hyperplasia; high fractions of
      proliferating cells are predictive of an early relapse.

PMID- 9577376
TI  - Accuracy and precision of the TAS analyser for near-patient INR testing by non
      pathology staff in the community.
AB  - AIMS: To assess the accuracy and precision of INR measurement by trained practice
      and district nursing staff using the Thrombolytic Assessment System (TAS)
      analyser. METHODS: Seventeen nurses from four practices were trained to measure
      INR using the TAS analyser on citrated capillary blood samples. Quality control
      (QC) consisted of: daily internal QC using normal and abnormal commercial
      plasmas; monthly local external QC scheme using fresh citrated venous blood; and
      registration of all analysers in the NEQAS (national external quality assessment
      scheme) main users scheme. RESULTS: Analysis of internal QC results demonstrated
      satisfactory interanalyser and intra-analyser precision with no evidence of
      analytical drift in any of the four practice analysers over an eight month
      period. Local and national external QC results confirmed the interanalyser
      precision but INR was underestimated by the TAS analysers compared with the CA
      1000 using either Diagen rabbit brain thromboplastin or Innovin, and with other
      NEQAS users. CONCLUSIONS: The TAS analyser has many features to commend it for
      use by nonpathology staff to determine INR. Local internal and external QC and
      entry into the NEQAS main users group are possible because the TAS analyses
      citrated plasma or blood. The TAS analyser underestimates INR when the geometric
      mean normal prothrombin time (GMNPT) is determined by conventional methods. A
      local correction factor can be introduced by adjusting the normal PT to give INR
      results comparable with the local laboratory. This is particularly desirable when
      INRs are measured using both near-patient and laboratory analytical systems on
      different occasions.

PMID- 9577378
TI  - A renin secreting ovarian steroid cell tumour associated with secondary
      polycythaemia.
AB  - A 67-year-old woman presented with dry skin, facial hair, hoarse voice, and
      weight gain. She was hypertensive (168/ 96 mm Hg), her haemoglobin concentration
      was 19 g/l, and haematocrit was 55.7%. The diagnosis of probable secondary
      polycythaemia was made. Blood testosterone concentration was 44 nmol/l (normal <
      5) and was not suppressed by dexamethasone, suggesting a neoplastic source rather
      than a pituitary abnormality. Transvaginal ultrasound revealed a hypoechoic solid
      mass in the left ovary suggestive of a solid ovarian tumour. Hysterectomy and
      bilateral salpingo-oophorectomy were performed following which testosterone
      concentration returned to normal. Immunocytochemistry provided evidence of renin
      synthesis. This is a case of an unusual steroid cell tumour that caused
      virilisation accompanied by symptoms of secondary polycythaemia presumably as a
      result of erythropoietin production. This is the second case of a steroid cell
      tumour with an erythropoietic effect and the first that shows evidence of renin
      synthesis.

PMID- 9577377
TI  - Development of a multiplex ARMS test for mutations in the HFE gene associated
      with hereditary haemochromatosis.
AB  - Genetic testing for hereditary haemochromatosis is likely to be a significant
      workload for diagnostic laboratories. The C282Y and H63D mutations in the HFE
      gene associated with hereditary haemochromatosis have previously been detected
      using a number of methods including alterations in the restriction digest pattern
      of polymerase chain reaction (PCR) amplified products. An amplification
      refractory mutation system (ARMS) has been developed that will simultaneously
      detect both hereditary haemochromatosis mutations. Comparison of the results
      obtained from the analysis of 46 samples referred for hereditary haemochromatosis
      testing showed no discrepancies between ARMS and restriction enzyme digestion.
      Furthermore, consistent results were obtained by ARMS from both blood and buccal
      mouthwash samples. The ARMS test is quicker and less expensive in terms of
      consumables and scientist time than restriction enzyme analysis, and is therefore
      suited to the routine diagnostic analysis of hereditary haemochromatosis.

PMID- 9577379
TI  - Sequential malt lymphomas of the stomach, small intestine, and gall bladder.
AB  - Low grade lymphomas of mucosa associated lymphoid tissue (MALT) are indolent
      neoplasms that, although tending to remain localised for many years, may spread
      to other mucosal sites. A 53 year old woman treated by total gastrectomy for low
      grade MALT lymphoma of the stomach developed a recurrence in the small bowel 18
      years later, and a further recurrence involving the gall bladder after three
      years in complete clinical remission after chemotherapy. In situ hybridisation
      showed that the small intestine and gall bladder recurrences had the same pattern
      of light chain restriction. Tumour from all three sites was shown to be derived
      from a single clone by the demonstration of an identical immunoglobulin heavy
      chain gene rearrangement by the polymerase chain reaction. The case illustrates
      the propensity of MALT lymphomas to "home" to mucosal sites and gives an insight
      into their behavior over an extended follow up.

PMID- 9577380
TI  - Familial pancreatic lymphoma.
AB  - Non-Hodgkin's lymphoma is not commonly a familial condition. This is believed to
      be the first two cases of primary pancreatic lymphoma within a single family. The
      two cases, a brother and sister, both presented in their 60s and were diagnosed
      histologically as having high grade B cell lymphoma affecting the pancreas, an
      uncommon primary site. Both responded well to treatment with chemotherapy and
      were in remission at the time of writing. On further investigation it was found
      that their mother also presented with a malignant lymphoma of cervical nodes 30
      years earlier and subsequently died of the disease.

PMID- 9577381
TI  - Manpower is another influential factor of necropsy rate.

PMID- 9577383
TI  - A cognitive affective role for the cerebellum.

PMID- 9577382
TI  - Lymphocytic gastritis and Helicobacter pylori: a Brazilian survey.

PMID- 9577384
TI  - Current concepts on the clinical features, aetiology and management of idiopathic
      cervical dystonia.
AB  - Idiopathic cervical dystonia (ICD) is the most common form of adult-onset focal
      dystonia. Previously, disagreement existed about whether ICD was a psychiatric
      illness, but the disorder is now viewed as a neurological illness and large
      clinical series have clarified the clinical features of the disease. At the time
      of diagnosis, extracervical dystonia is found in approximately 20% of patients,
      and there may be a concomitant head or hand tremor. Importantly, adult-onset ICD
      does not become generalized, although there may be segmental spread and pain may
      increase independently of the dystonia. While 10-20% of patients may experience
      remission, nearly all patients relapse within 5 years and are left with
      persistent disease. The aetiology of ICD is unknown, but there has been much
      progress in clarifying the genetic abnormality in families with inherited adult
      onset cervical dystonia; linkage to chromosome 18p has been demonstrated in one
      family, and the DYT1 locus has been excluded in two other families. Painful
      trauma may be involved in the pathogenesis of ICD. Painful stimuli are received
      and processed by the basal ganglia, and the synaptic changes provoked by pain may
      lead to the abnormal physiology underlying dystonia. Consistent with this idea
      are experiments which demonstrate that altered sensory input leads to plasticity
      of the motor cortex, and those that explore the 'tonic vibration reflex' in
      patients with dystonia. Another theory suggests that a primary vestibular
      abnormality is responsible for ICD. Botulinum toxin is the most effective
      treatment for ICD. Roughly 75% of patients improve, and a response is generally
      seen within the first week. However, many questions remain regarding the optimal
      technique of administration. The development of neutralizing antibodies occurs in
      at least 5-10% of patients, and appears to be related both to dosage and to the
      interval between treatments. Side-effects are generally mild and result from the
      action of the toxin in the periphery. If the response to botulinum toxin is not
      adequate, anticholinergics, benzodiazepines, baclofen and other medications are
      used as adjunctive therapy. Surgical therapies are available for the treatment of
      ICD but are reserved for patients refractory to conservative measures.

PMID- 9577385
TI  - The cerebellar cognitive affective syndrome.
AB  - Anatomical, physiological and functional neuroimaging studies suggest that the
      cerebellum participates in the organization of higher order function, but there
      are very few descriptions of clinically relevant cases that address this
      possibility. We performed neurological examinations, bedside mental state tests,
      neuropsychological studies and anatomical neuroimaging on 20 patients with
      diseases confined to the cerebellum, and evaluated the nature and severity of the
      changes in neurological and mental function. Behavioural changes were clinically
      prominent in patients with lesions involving the posterior lobe of the cerebellum
      and the vermis, and in some cases they were the most noticeable aspects of the
      presentation. These changes were characterized by: impairment of executive
      functions such as planning, set-shifting, verbal fluency, abstract reasoning and
      working memory; difficulties with spatial cognition including visual-spatial
      organization and memory; personality change with blunting of affect or
      disinhibited and inappropriate behaviour; and language deficits including
      agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum
      produced only minor changes in executive and visual-spatial functions. We have
      called this newly defined clinical entity the 'cerebellar cognitive affective
      syndrome'. The constellation of deficits is suggestive of disruption of the
      cerebellar modulation of neural circuits that link prefrontal, posterior
      parietal, superior temporal and limbic cortices with the cerebellum.

PMID- 9577386
TI  - Abnormal merosin in adults. A new form of late onset muscular dystrophy not
      linked to chromosome 6q2.
AB  - We have identified seven patients (including two sib pairs) with a predominantly
      late onset limb-girdle muscular dystrophy in whom an absence of merosin was noted
      on immunoblotting. Merosin immunocytochemistry was normal, and no abnormalities
      were detected on immunostaining for the various proteins known to be involved in
      the limb-girdle muscular dystrophies (alpha, beta, gamma, delta sarcoglycan and
      calpain 3). Apart from one patient, where muscle problems began in childhood,
      reported age at onset of muscle weakness involving initially the proximal muscles
      of the lower limbs ranged from 17 to 40 years. The pattern of muscle involvement
      was similar from patient to patient, with hypertrophy of at least the calf
      muscles, absence of scapular winging and predominant involvement of hip flexors
      and adductors and hamstrings more than quadriceps. Serum creatine kinase in all
      patients was at least 10 times normal, and muscle biopsies showed non-specific
      dystrophic features. We believe that the patients described here may represent a
      genetically distinct subset within the limb-girdle muscular dystrophy group.

PMID- 9577387
TI  - The natural history of degenerative ataxia: a retrospective study in 466
      patients.
AB  - The aim of the present study was (i) to compare disease progression and survival
      in different types of degenerative ataxia, and (ii) to identify variables that
      may modify the rate of disease progression. We included patients suffering from
      Friedreich's ataxia (FRDA, n = 83), early onset cerebellar ataxia (EOCA, n = 30),
      autosomal dominant cerebellar ataxia (ADCA) type I (ADCA-I, n = 273), ADCA-III (n
      = 13) and multiple system atrophy (MSA, n = 67). Molecular genetic testing
      allowed us to assign 202 ADCA-I patients to one of the following subgroups:
      spinocerebellar ataxia type I (SCAI, n = 36), SCA2 (n = 56) and SCA3 (n = 110).
      To assess disease progression we defined the following disease stages: stage 0 =
      no gait difficulties; stage 1 = disease onset, as defined by onset of gait
      difficulties; stage 2 = loss of independent gait; stage 3 = confinement to
      wheelchair; stage 4 = death. Disease progression was most rapid in MSA,
      intermediate in FRDA, ADCA-I and ADCA-III and slowest in EOCA. The rate of
      progression was similar in SCA1, SCA2 and SCA3. The CAG repeat length was a
      significant risk factor for faster progression in SCA2 and SCA3, but not in SCA1.
      In FRDA, the time until confinement to wheelchair was shorter in patients with
      earlier disease onset, suggesting that patients with long GAA repeats and early
      disease onset have a poor prognosis. Female gender increased the risk of becoming
      dependent on walking aids or a wheelchair, but it did not influence survival in
      FRDA, SCA3 and MSA. In SCA2, female gender was associated with shortened
      survival. In MSA, later age of onset increased the risk of rapid progression and
      death.

PMID- 9577388
TI  - Autosomal dominant hereditary spastic paraparesis with cognitive loss linked to
      chromosome 2p.
AB  - A family initially considered to have 'pure' autosomal dominant hereditary
      spastic paraparesis (HSP), was found on neuropsychological testing to have
      evidence of late onset cognitive impairment. This family showed genetic linkage
      to the SPG4 locus on chromosome 2p previously reported for pure HSP. Of 56 living
      members, 44 were examined, 30 of whom were > 30 years of age and 12 members were
      found to be affected with HSP including four asymptomatic cases. One other family
      member (III-5), aged 62 years, died prior to this study of a 4-year dementing
      illness. Neuropsychological assessment of 11 affected members and 11 matched,
      unaffected, family controls showed no significant differences between the two
      groups. However, the neuropsychological test profile in four of 11 affected
      members tested (mean age 47.2 years) and one of 11 family controls (mean age 41.5
      years) showed global cognitive impairment. The pattern of cognitive dysfunction
      was the same for all five family members identified and was similar to that found
      in subcortical dementia. The presence of cognitive impairment appeared to be
      related to age and not the severity of the paraplegia. Both the severity of the
      paraplegia and the age of onset (21-60 years) varied considerably in this family.

PMID- 9577389
TI  - The neural substrates of memory systems impairment in Alzheimer's disease. A PET
      study of resting brain glucose utilization.
AB  - The aim of this study was to determine the neuronal basis for memory impairment
      in Alzheimer's disease by taking advantage of the clinical and metabolic
      heterogeneity of this pathology. To this end, 19 patients satisfying the
      NINCDSADRDA criteria for probably Alzheimer's disease of mild-to-moderate
      severity underwent a detailed examination of the five memory systems according to
      Tulving's model, together with a PET measurement of resting regional cerebral
      glucose utilization (CMRGlc). Compared with controls, the patients as a group
      showed the expected memory and metabolic profiles of impairment. Correlations
      (corrected for the effects of ageing) were calculated between memory scores and
      CMRGlc (normalized by the vermis CMRGlc) using two methods: (i) the classic
      regions-of-interest method, based on a priori hypotheses and individual
      coregistered structural MRI; and (ii) the statistical parametric mapping method
      which allows a systematic voxel-by-voxel analysis, in a more descriptive and
      exploratory way. Significant correlations were above chance levels and largely
      consistent between the two methods. They were almost exclusively positive (i.e.
      in the neurobiologically expected direction) and their distribution showed
      striking differences according to each memory system. Thus, verbal episodic
      memory impairment was related to changes in a large neuronal network including
      not only the limbic structures (mesial temporal cortex, thalamus and cingulate
      gyrus, with left side predominance) but also the parietotemporal and frontal
      association cortices of the right hemisphere, possibly on a compensatory basis.
      Regardless of modality, short-term memory tests were mainly correlated with
      bilateral activity in posterior association cortex, and also with activity in
      left prefrontal cortex for the visuospatial span, possibly indicating essentially
      uniform strategies for the performance of the different tasks. As predicted,
      semantic memory scores correlated with activity in temporoparietal and frontal
      association cortices of the left hemisphere, and also with activity in left
      cingulate cortex. Thus, for episodic, short-term and semantic memory, many
      findings fit classical neuropsychology, while most of the less expected ones were
      consistent with recent results from functional neuro-imaging in healthy subjects,
      notably with the hemispheric encoding/ retrieval asymmetry (HERA) model; only few
      findings suggested possible reorganization processes and/or recourse to
      unexpected cognitive strategy. Finally, only negative correlations were found for
      perceptual priming and procedural memory; although they could arise by chance,
      some of these unexpected findings give rise to interesting hypotheses about the
      cognitive relationships between the most and least affected memory systems. This
      study documents the validity and usefulness of our approach in unravelling the
      neural substrates of cognitive impairment in brain pathology without focal tissue
      loss such as that seen in neurodegenerative diseases.

PMID- 9577390
TI  - Category specific semantic loss in dementia of Alzheimer's type. Functional
      anatomical correlations from cross-sectional analyses.
AB  - In the context of focal brain injury, selective loss of semantic knowledge in the
      domain of either natural kinds or artefacts is usually considered to reflect the
      differential importance of temporal and frontoparietal regions to the
      representations of perceptual and functional attributes, respectively. It is
      harder to account far as a feature of a more diffuse process, and previous cross
      sectional analyses of patients with dementia of Alzheimer's type (DAT) have
      differed over whether category effects occur. In our series of 58 patients with
      probable DAT, we demonstrated a significant group advantage for artefacts, and
      explored possible reasons for the inconsistency of this finding in other studies.
      A multiple single-case strategy revealed not only individuals with consistent
      advantages for artefacts but also individuals with consistent advantages for
      natural kinds. By ranking the individuals according to measures of naming
      performance and global intellectual ability, we showed that the strength of the
      group advantage for artefacts was dependent on the former but not the latter
      variable. The findings are discussed in the context of two competing theories of
      semantic breakdown in DAT. One differentiates between domains of knowledge in
      terms of the structure of semantic representations within a single distributed
      network; the other emphasizes the importance of different brain regions in the
      category distinction. We conclude that our findings are in keeping with the
      predictions of the latter hypothesis.

PMID- 9577391
TI  - Influence of somatosensory input on paroxysmal activity in benign rolandic
      epilepsy with 'extreme somatosensory evoked potentials'.
AB  - We studied six patients suffering from benign rolandic epilepsy of childhood with
      central temporal spikes who presented so-called 'extreme somatosensory evoked
      potentials (SEPs)' following peripheral somatosensory stimulation. Stimuli were
      delivered to the fingers of one hand using both a triggered tendon hammer and low
      intensity electrical stimulation. The electrical stimulation was delivered in
      sequences in different conditions (i.e. random order, 1, 3 and 10 Hz). Both
      tapping and electrical stimulation produced scalp evoked potentials in all
      subjects, characterized by a spike followed by a slow wave, similar in morphology
      and scalp distribution to the spontaneously occurring spikes. This paroxysmal
      activity was sensitive to stimulus rate; the number of evoked spikes was
      inversely related to the frequency of stimulation, being maximal at 1 Hz and
      disappearing at high frequencies (10 Hz). Spontaneous spikes disappeared during
      high-frequency stimulation but were present during low-frequency stimulation.
      Averaged SEPs at 3-Hz stimulation showed a late high-amplitude component,
      identical in morphology and distribution to the single evoked spike. We therefore
      conclude that, in these subjects, the so-called 'extreme SEPs' are evoked spikes
      and that evoked and spontaneous spikes share common cortical sensorimotor
      generators. The evidence that these generators can be influenced by afferent
      input provides important information regarding the functional mechanisms involved
      in modulating cortical excitability in benign rolandic epilepsy. Moreover, we
      suggest that peripheral electrical stimulation can be used as an additional
      activation test in this kind of epilepsy.

PMID- 9577392
TI  - Neuropsychological, neurological and functional outcome following pallidotomy for
      Parkinson's disease. A consecutive series of eight simultaneous bilateral and
      twelve unilateral procedures.
AB  - Intellectual, psychological and functional outcomes were evaluated in a
      consecutive series of 20 Parkinsonian patients who had unilateral (UPVP) or
      simultaneous bilateral posteroventral pallidotomy (BPVP) using Image Fusion and
      Stereoplan (Radionics Inc., Boston, Mass., USA) with stimulation for lesion
      localization. Comprehensive baseline and 3-month postoperative neuropsychological
      and neurological assessment protocols were administered together with
      questionnaire measures of functional disability, quality of life and
      psychological symptomatology. Changes in patients' clinical presentation and
      scores on psychometric tests, questionnaires and observational rating scales were
      then examined. We observed no new neuropsychiatric sequelae directly related to
      pallidotomy. Cognitive sequelae were restricted to selective reductions in
      categorical verbal fluency following UPVP (P < 0.001) and BPVP (P < 0.01) and a
      reduction in phonemic verbal fluency following BPVP (P < 0.01); these changes
      were not reported subjectively. A fall in diadochokinetic rates (P < 0.01) and
      some subjective reports of a worsening in pre-existing dysarthria, hypophonia and
      hypersalivation/drooling following BPVP also suggested changes in speech motor
      apparatus; however, these changes did not have significant functional
      consequences. There was one case of more generalized cognitive impairment
      following BPVP. We also observed significant symptomatic improvement on
      neurological rating scales; following UPVP, Total Unified Parkinson's Disease
      Rating Scale (UPDRS) scores improved by 27% (P < 0.01) and following BPVP the
      improvement was 53% (P < 0.05). Patients' perceptions of reduced postoperative
      functional disability and improvements in 'quality of life' also achieved
      statistical significance on a number of both physical and psychosocial
      questionnaire subscales.

PMID- 9577393
TI  - Perceptual and oculomotor effects of neck muscle vibration in vestibular
      neuritis. Ipsilateral somatosensory substitution of vestibular function.
AB  - Afferent cervical somatosensory input may substitute for absent vestibular
      information as part of central vestibular compensation after unilateral
      peripheral vestibular deficit. In order to determine the particular contribution
      of neck muscle spindles to the perception of body orientation and to the
      oculomotor system, we measured (i) the subjective visual straight ahead (SVA) by
      psychophysical tests and (ii) the changes in eye position by video-nystagmography
      during unilateral stimulation of the posterior neck muscles by vibration (100
      Hz). Twenty-five patients with subacute unilateral vestibular lesion (vestibular
      neuritis) and 25 controls participated in the study. Vibration elicited a
      horizontal displacement of SVA towards the side of stimulation in all subjects.
      Mean displacement (+/- SD) was 3.28 +/- 2.96 degrees for right-side and 3.45 +/-
      2.93 degrees for left-side stimulation in controls. Muscle stimulation on the
      patients' lesion side induced a significantly higher displacement (11.51 +/- 6.63
      degrees) than contralateral stimulation (3.04 +/- 2.95 degrees, P < 0.01, paired
      Student's t test). The mean difference during stimulation between the two sides
      in the patients was 8.02 +/- 5.52 degrees; in the controls, however, it was only
      0.74 +/- 0.47 degree (P < 0.001, Student's t test). This asymmetry increased
      gradually in patients over a period of weeks, reaching a maximum at days 60-80
      and declining thereafter. Videonystagmography revealed that ipsilateral
      stimulation in patients induced large horizontal eye deviations of up to 25
      degrees towards the side of the lesion (9.1 +/- 7.6 degrees, n = 18).
      Contralateral stimulation induced only small shifts, which were within the range
      of controls. The correlation coefficient between displacement of the SVA and
      change in eye position was high (r = 0.94, P < 0.0001), indicating that the shift
      of SVA is the perceptual correlate of the directional change of gaze in space.
      This interpretation was supported by two control experiments in which the subject
      was required to (i) indicate the subjective straight ahead by finger-pointing
      with the eyes closed and (ii) adjust SVA when looking through horizontally
      reversing prisms. Vibration of neck muscles caused almost no displacement of the
      SVA when it was indicated by pointing with the eyes closed, but reversed the
      direction of the displacement if the subject wore reversing prisms. In summary,
      our data showed: (i) an increase in muscle spindle input following unilateral
      vestibular lesion; (ii) this increase is asymmetrical, restricted to the affected
      side, and gradually builds up over weeks; and (iii) the perceived effects during
      vibration are secondary to changes in eye position rather than changes in
      cortical representation of body orientation. This is the first study to
      demonstrate a unilateral increase in somatosensory weight, which substitutes for
      missing vestibular input.

PMID- 9577394
TI  - Brain and spinal cord abnormalities in multiple sclerosis. Correlation between
      MRI parameters, clinical subtypes and symptoms.
AB  - We investigated various magnetic resonance MRI parameters for both brain and
      spinal cord to see if any improved the clinicoradiological correlation in
      multiple sclerosis. Ninety-one multiple sclerosis patients (28 relapsing
      remitting, 32 secondary progressive and 31 primary progressive) were imaged using
      conventional T1, proton density- and T2-weighted MRI of the brain and spinal
      cord. Focal brain and spinal cord lesion load was scored, as were diffuse signal
      abnormalities, brain ventricular volume and spinal cord cross-sectional area.
      Clinical measures included the expanded disability status scale (EDSS), the
      functional systems score and a dedicated urology complaint questionnaire.
      Secondary progressive patients differed from relapsing-remitting and primary
      progressive patients by a larger number of hypointense T1 lesions in the brain,
      ventricular enlargement and spinal cord atrophy. Primary progressive patients
      more often had diffuse abnormalities in the brain and/or spinal cord than did
      relapsing-remitting and secondary progressive patients. In the entire study
      population, EDSS correlated with both brain and spinal cord MRI parameters, which
      were independent. The urological complaint score correlated only with spinal cord
      MRI parameters. In relapsing-remitting and secondary progressive multiple
      sclerosis, the correlation between MRI and clinical parameters was better than in
      the entire population. In this subgroup EDSS variance could be explained best by
      T1 brain lesion load, ventricle volume and spinal cord cross-sectional area. In
      the primary progressive subgroup the clinicoradiological correlation was weak for
      brain parameters but was present between spinal cord symptoms and spinal cord MRI
      parameters. In conclusion, the different brain and spinal cord MRI parameters
      currently available revealed considerable heterogeneity between clinical subtypes
      of multiple sclerosis. In relapsing-remitting and secondary progressive multiple
      sclerosis both brain and spinal cord MRI may provide a tool for monitoring
      patients, while in primary progressive multiple sclerosis the clinicoradiological
      correlation is weak for brain imaging.

PMID- 9577395
TI  - Semicircular canal plane head impulses detect absent function of individual
      semicircular canals.
AB  - We studied the human vestibulo-ocular reflex (VOR) in response to head
      'impulses': brief, unpredictable, passive, high-acceleration (up to 4000
      degrees/s2), low-amplitude (20-30 degrees) head rotations. We delivered the head
      impulses approximately in the plane of the semicircular canal (SCC) being tested.
      To test the anterior and posterior SCCs, the head impulses were delivered in a
      diagonal plane, midway between the frontal (roll) and sagittal (pitch) planes. We
      recorded head and eye position in three dimensions with scleral search coils in
      nine normal subjects, seven patients following unilateral surgical vestibular
      neurectomy and three patients following unilateral posterior SCC occlusion. In
      the post-surgical patients we demonstrated a severe, permanent VOR gain deficit
      (0.2-0.3) for head impulses directed toward any single non-functioning SCC. The
      sensitivity of the test depends on the physiological properties of primary
      vestibular afferents, and its specificity depends on the anatomical orientation
      of the SCCs. The diagonal head impulse is the first test of individual vertical
      SCC function in humans, and together with the horizontal head impulse, forms a
      comprehensive battery of SCC-plane tests. These canal-plane impulses could be
      useful in evaluating patients with vertigo or other vestibular disorders.

PMID- 9577396
TI  - Plasticity of plasticity? Changes in the pattern of perceptual correlates of
      reorganization after amputation.
AB  - We report a follow-up study on seven arm amputees in whom magnetic source imaging
      had originally revealed a strong correlation between the amount of cortical
      invasion of the deafferented cortex and the amount of pain evoked sensation
      mislocalized to the phantom limb. This re-examination was performed in order to
      corroborate the phenomenon of mislocalization. On follow-up examination for
      mislocalization 4 weeks later, a close correlation had remained between the
      original amount of cortical representational reorganization of the amputation
      zone (at the first examination) and the number of sites from where painful
      stimuli evoked sensations referred to the phantom limb, i.e. the amount of
      perceptual mislocalization, at the second examination. However, contrary to our
      expectation, the topography of referred sensation had completely changed in every
      patient. These results suggest that while the overall extent of reorganization is
      a rather stable phenomenon, the concomitant changes in the pattern of sensory
      processing are not. This may be due to the fact that alterations of sensory
      processing are not hardwired, but are rather mediated by an extensive and
      interconnected neural network with fluctuating synaptic strengths. This mechanism
      may be of importance for neurological rehabilitation.

PMID- 9577397
TI  - The co-ordination and phasing of a bilateral prehension task. The influence of
      Parkinson's disease.
AB  - Parkinson's disease patients and control subjects performed a simultaneous
      bilateral reach-to-grasp task to two different sized objects and then pulled the
      two objects apart. The first phase of the task (reaching-to-grasp) allowed us to
      examine the issue that impairments in simultaneous movements for Parkinson's
      disease patients are seen in some tasks but not in others. It is suggested that
      the reason for this selective impairment is that Parkinson's disease compromises
      the ability to control multiple task-level degrees of freedom independently and
      concurrently (task-level degrees of freedom are defined as the number of
      independent parameters that require specification to perform the task). The first
      phase was used to test the hypothesis that Parkinson's disease results in a
      reduction of degrees of freedom that are independently controlled. It was
      predicted that Parkinson's disease patients would produce similar (homologous)
      movements of the two limbs (a symmetrical pattern) if the target objects have
      different accuracy requirements when they reach bilaterally to the two objects.
      For bilateral reaches for two different-size objects, only the control group
      showed reliably different patterns in the two limbs (asymmetrical pattern), while
      the Parkinson's disease group displayed a symmetrical pattern. These results
      provide support for the hypothesis that Parkinson's disease patients have a
      reduced capability to control multiple task-level degrees of freedom. The second
      phase of the task, which involved a transition from position control (reaching-to
      grasp) to force control (stabilizing and pulling) was used to examine the ability
      of Parkinson's disease patients to make transitions between movement tasks and
      force control. In contrast to control subjects, Parkinson's disease patients
      produced staircase patterns for grip and load forces. Furthermore, a breakdown in
      the parallel co-ordination between grip and load force was observed for
      Parkinson's disease patients. These data suggest that Parkinson's disease
      disrupts the normal feedforward operations responsible for the co-ordination
      between grip and load forces.

PMID- 9577398
TI  - Bimanual co-ordination in Parkinson's disease.
AB  - The basal ganglia may be involved in bimanual co-ordination. Parkinson's disease
      (which impairs basal ganglia output) is clinically reported to cause difficulties
      in the performance of co-ordinated bimanual movements. Nevertheless, any bimanual
      co-ordination difficulties may be task specific, as experimental observations are
      equivocal. To infer the role of the basal ganglia in co-ordinating the two arms,
      this study investigated the bimanual co-ordination of patients with Parkinson's
      disease. Sixteen Parkinson's disease patients and matched control subjects
      performed a bimanual cranking task, at different speeds (1 and 2 Hz) and phase
      relationships. All subjects performed the required bimanual in-phase movement on
      a pair of cranks, at fast (2 Hz) and slow (1 Hz) speeds. However, the Parkinson's
      disease patients were unable to perform the asymmetrical anti-phase movement, in
      which rotation of the cranks differed by 180 degrees, at either speed; but
      instead reverted to the in-phase symmetrical movement. For Parkinson's disease
      patients, performance of the in-phase movement was more accurate and stable when
      an external timing cue was used; however, for anti-phase movement, the external
      cue accentuated the tendency for patients to revert to more symmetrical, in-phase
      movements.

PMID- 9577399
TI  - The reaching movements of patients with Parkinson's disease under self-determined
      maximal speed and visually cued conditions.
AB  - Two-dimensional kinematic analysis was performed of the reaching movements that
      six subjects with Parkinson's disease and six healthy subjects produced under
      self-determined maximal speed and visually cued conditions. Subjects were
      required to reach as fast as possible to grasp a ball (i) that was fixed
      stationary in the centre of a designated contact zone on an inclined ramp (self
      determined maximal speed condition), or (ii) that rolled rapidly from left to
      right down the incline and into the contact zone (visually cued condition).
      Parkinson's disease subjects displayed bradykinesia when performing maximal speed
      reaches to the stationary ball, but not when they reached for the moving ball. In
      response to the external driving stimulus of the moving ball, Parkinson's disease
      subjects showed the ability to exceed their self-determined maximal speed of
      reaching and still maintain a movement accuracy that was comparable to that of
      healthy subjects. Thus, the bradykinesia of Parkinson's disease subjects did not
      seem to be the result of a basic deficit in their force production capacity or to
      be a compensatory mechanism for poor movement accuracy. Instead, bradykinesia
      appeared to result from the inability of Parkinson's disease subjects to maximize
      their movement speed when required to internally drive their motor output. The
      occasional failure of Parkinson's disease subjects to successfully grasp the
      moving ball suggested errors of coincident anticipation and impairments in grasp
      performance rather than limitations in the speed or accuracy of their reaches.
      These results are discussed in relation to the notion that the motor circuits of
      the basal ganglia play an important role in the modulation of internally
      regulated movements.

PMID- 9577400
TI  - The Italian Guillain-Barre Study Group. The prognosis and main prognostic
      indicators of Guillain-Barre syndrome: a multicentre prospective study of 297
      patients.

PMID- 9577402
TI  - The Metamorphosis.

PMID- 9577401
TI  - Evidence for lateral premotor and parietal overactivity in Parkinson's disease
      during sequential and bimanual movements. A PET study.

PMID- 9577403
TI  - A case of extraordinary exostoses on the back of a boy. 1740. John Freke (1688
      1756).

PMID- 9577404
TI  - Fibrodysplasia (myositis) ossificans progressiva. Clinical lessons from a rare
      disease.
AB  - Fibrodysplasia (myositis) ossificans progressiva is a rare dominantly inherited
      disorder, in which defects in skeletal patterning particularly affecting the big
      toes, are associated with progressive endochondral ossification of the large
      striated muscles in a specific order leading to prolonged disability. A recent
      series of 28 patients studied for as many as 24 years exemplifies the
      presentation and course of this disease. Painful swelling of muscles (myositis)
      leading to ossification began at a mean age of 4.6 years (range, 0-16 years)
      initially in the neck and upper spine (in 25 subjects) and later around the hips,
      other major joints, and jaw. The rate and extent of disability was unrelated to
      the time of onset. No form of treatment produced consistent benefit. Despite the
      unique clinical features, the initial diagnosis of fibrodysplasia ossificans
      progressiva was often wrong and usually considerably delayed. Mistaken histologic
      diagnoses such as soft tissue sarcoma or fibromatosis could lead to inappropriate
      treatment.

PMID- 9577405
TI  - The genetics of fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva is an autosomal dominant disorder. Most
      cases are due to new gene mutations because people with fibrodysplasia ossificans
      progressiva have markedly reduced reproductive fitness. The gene or genes
      responsible for this disorder are unknown.

PMID- 9577406
TI  - Acute lymphocytic infiltration in an extremely early lesion of fibrodysplasia
      ossificans progressiva.
AB  - A 2-year-old child with fibrodysplasia ossificans progressiva underwent a muscle
      biopsy of a very early lesion, and had findings that showed the earliest stage
      ever seen in the histopathology of fibrodysplasia ossificans progressiva. This
      very early stage consisted of intense perivascular lymphocytic infiltration into
      normal appearing skeletal muscle. A nearly identical histopathologic sequence was
      noted in a cat with phenotypic features similar to those of fibrodysplasia
      ossificans progressiva in humans. These new findings represent the earliest
      documented changes that have ever been noted in fibrodysplasia ossificans
      progressiva, and provide further histopathologic support for the recent discovery
      that lymphocytes may play a role in the pathogenesis of heterotopic ossification
      in fibrodysplasia ossificans progressiva.

PMID- 9577407
TI  - Bone morphogenetic protein and bone morphogenetic protein gene family in bone
      formation and repair.
AB  - The bone morphogenetic proteins are secreted signalling molecules that belong to
      the transforming growth factor beta family of growth and differentiation factors.
      Individual bone morphogenetic proteins are prominent at many sites during
      embryogenesis and are likely to be key regulators of early development and
      organogenesis. In vertebrates, one of the functions of bone morphogenetic like
      proteins is to induce formation of bone, cartilage, and connective tissues
      associated with the skeleton. This osteoinductive ability has led to the use of
      bone morphogenetic proteins as therapeutic agents for creation of new bone useful
      in treatment of skeletal injuries and diseases, and in oral and maxillofacial
      applications.

PMID- 9577408
TI  - Characterization of bone morphogenetic protein 4 receptor in fibrodysplasia
      ossificans progressiva.
AB  - Bone morphogenetic protein 4, a potent osteogenic morphogen, has been implicated
      in fibrodysplasia ossificans progressiva because it is uniquely overexpressed in
      lymphoblastoid cells and preosseous fibroproliferative lesional cells of patients
      with fibrodysplasia ossificans progressiva. Bone morphogenetic protein 4 signals
      through a heteromeric complex of serine/ threonine kinase receptors (type I and
      type II) on the surface of responding cells. Semi-quantitative competitive
      reverse transcription polymerase chain reaction was used to quantitate steady
      state levels of messenger ribonucleic acid expression for bone morphogenetic
      protein 4 and the bone morphogenetic protein receptors. These data confirmed the
      previous finding of elevated steady state levels of bone morphogenetic protein 4
      messenger ribonucleic acid in lymphoblastoid cell lines of affected individuals
      in a family that exhibited autosomal dominant inheritance of fibrodysplasia
      ossificans progressiva. There were no differences in the steady state levels of
      messenger ribonucleic acid for either the Type I or Type II bone morphogenetic
      protein 4 receptors between affected and unaffected individuals in that same
      family. The presence of bone morphogenetic protein 4 receptor messenger
      ribonucleic acid in fibrodysplasia ossificans progressiva lesional tissue and
      unaffected muscle tissue and demonstrates the deregulation of bone morphogenetic
      protein 4 messenger ribonucleic acid in fibrodysplasia ossificans progressiva.
      These data support the hypothesis that the molecular basis of bone morphogenetic
      protein 4 signaling is abnormal in fibrodysplasia ossificans progressiva.

PMID- 9577409
TI  - Differential expression of bone and cartilage related genes in fibrodysplasia
      ossificans progressiva, myositis ossificans traumatica, and osteogenic sarcoma.
AB  - Fibrodysplasia ossificans progressiva, myositis ossificans traumatica, and
      osteogenic sarcoma are representative genetic, traumatic, and neoplastic
      disorders of osteogenesis, respectively. However, the pathology, pathophysiology,
      and natural history of the disorders differ substantially. Gene expression
      related to bone induction was studied in these disorders. Primary cell lines
      established from lesional tissues derived from each of these disorders expressed
      different patterns of protooncogenes, bone morphogenetic protein genes, and bone
      phenotype specific genes. The osteogenic sarcoma cell line expressed the entire
      repertoire bone morphogenetic proteins 1 to 7, c-fos and c-jun messenger
      ribonucleic acids. Myositis ossificans traumatica cells expressed phenotype
      markers similar to those of the osteogenic sarcoma cells, and expressed bone
      morphogenetic proteins 1, 4, and 6 and c-fos messenger ribonucleic acids, but not
      c-jun messenger ribonucleic acid. Fibrodysplasia ossificans progressiva early
      lesional cells demonstrated specific over-expression of bone morphogenetic
      protein 4 messenger ribonucleic acid. Differential expression of genes related to
      osteogenesis have important implications for understanding the earliest molecular
      events in normal and dysregulated osteogenesis in humans.

PMID- 9577410
TI  - Mutational screening of the bone morphogenetic protein 4 gene in a family with
      fibrodysplasia ossificans progressiva.
AB  - Bone morphogenetic proteins have been proposed as candidate genes for
      fibrodysplasia ossificans progressiva. Bone morphogenetic protein 4 is
      overexpressed in cells derived from these patients. The bone morphogenetic
      protein 4 genes from a family showing autosomal dominant inheritance of
      fibrodysplasia ossificans progressiva have been screened for mutations by single
      strand conformation polymorphism analysis and deoxyribonucleic acid sequencing.
      The exon coding regions and splice junctions of the bone morphogenetic protein 4
      gene have been examined for polymorphisms in all five family members. However, no
      mutation was discovered in these messenger ribonucleic acid and protein coding
      regions or in the splice junctions of affected or unaffected family members. In
      addition, approximately 1.5 kb of upstream flanking sequences also were examined.
      Neutral polymorphisms were identified in the upstream flanking region of the bone
      morphogenetic protein 4 gene. Although this study has not identified any
      mutations in the bone morphogenetic protein 4 gene that are correlated with the
      occurrence of fibrodysplasia ossificans progressiva, the bone morphogenetic
      protein 4 gene cannot yet be excluded from consideration as the genetic cause of
      this disorder because a mutation could be present in unexamined regulatory
      sequences of this gene.

PMID- 9577411
TI  - Urinary basic fibroblast growth factor. A biochemical marker for preosseous
      fibroproliferative lesions in patients with fibrodysplasia ossificans
      progressiva.
AB  - Angiogenesis is a prominent histopathologic feature of preosseous
      fibroproliferative lesions in patients who have fibrodysplasia ossificans
      progressiva. Basic fibroblast growth factor is an extremely potent in vivo
      stimulator of angiogenesis, and has been implicated in the growth of solid
      tumors. An enzyme linked immunosorbent assay for basic fibroblast growth factor
      was performed on urine samples from patients who had active (n = 28) and inactive
      (n = 39) fibrodysplasia ossificans progressiva, and compared with urine samples
      from normal age and gender matched control subjects (n = 54). Median basic
      fibroblast growth factor levels were 2705 pg/g of creatinine in the normal
      control group, 5058 pg/g of creatinine in patients with inactive fibrodysplasia
      ossificans progressiva (no significant difference), and 8793 pg/g of creatinine
      in patients with active fibrodysplasia ossificans progressiva. Female subjects,
      both normal and with fibrodysplasia ossificans progressiva, had higher levels of
      urinary basic fibroblast growth factor than did male subjects. There was no
      correlation of urinary basic fibroblast growth factor levels with age or severity
      of preexisting disability. These data document an elevation of urinary basic
      fibroblast growth factor during acute flareups of fibrodysplasia ossificans
      progressiva and provide a biochemical basis for considering antiangiogenic
      therapy for inhibiting endochondral osteogenesis in this disorder.

PMID- 9577412
TI  - Human leukocyte antigen B27 allele is not correlated with fibrodysplasia
      ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva is a rare heritable disorder of connective
      tissue characterized by skeletal malformations and by progressive heterotopic
      ossification. It has been suggested that the genetic marker human leukocyte
      antigen B27 may be associated with fibrodysplasia ossificans progressiva, as it
      is with ankylosing spondylitis, another disorder with less severe hyperostosis.
      Genomic deoxyribonucleic acid from 23 classically affected patients with
      fibrodysplasia ossificans progressiva was screened for the human leukocyte
      antigen B27 allele by polymerase chain reaction. Only two of the 23 patients (9%)
      with fibrodysplasia ossificans progressiva who were examined showed the presence
      of the human leukocyte antigen B27 allele, an incidence that corresponds to the
      8% frequency of individuals within the general population not affected with
      ankylosing spondylitis. These data suggest that the human leukocyte antigen B27
      allele does not occur more commonly in the genotype of patients with
      fibrodysplasia ossificans progressiva than in the general population, and that
      the pathogenesis of heterotopic bone in fibrodysplasia ossificans progressiva
      differs from that of ankylosing spondylitis and other human leukocyte antigen B27
      positive disorders.

PMID- 9577413
TI  - Animal models of heterotopic ossification.
AB  - Heterotopic ossification is often a severe clinical complication of joint
      arthroplasty, neurologic trauma, and muscle injury. In rare genetic disorders,
      such as fibrodysplasia ossificans progressiva, heterotopic ossification can be
      crippling and often leads to premature death. Reliable animal models of
      heterotopic ossifications that mimic pathologies seen in man would be invaluable
      for the development of new treatments to combat heterotopic ossification. Various
      methods used to induce heterotopic ossification in animals including the use of
      bone morphogenetic proteins, urinary tract epithelia, and transformed cell lines
      are described. Genetic animal models of heterotopic ossification and various
      miscellaneous examples of heterotopic ossification in animals are described.
      Finally, the use of transgenic mice to manipulate bone morphogenetic protein
      expression is discussed as a possible future animal model of heterotopic
      ossification.

PMID- 9577414
TI  - Embryonic overexpression of the c-Fos protooncogene. A murine stem cell chimera
      applicable to the study of fibrodysplasia ossificans progressiva in humans.
AB  - Murine embryonic overexpression of the c-fos protooncogene leads to early
      postnatal heterotopic chondrogenesis and osteogenesis with phenotypic features
      similar to those seen in children who have the disabling heritable disease
      fibrodysplasia ossificans progressiva. The overexpression of Fos in embryonic
      stem cell chimeras leads to heterotopic endochondral osteogenesis at least in
      part through a bone morphogenetic protein 4 mediated signal transduction pathway.
      In contrast, early fibrodysplasia ossificans progressiva lesions express abundant
      bone morphogenetic protein 4, without abundant expression of c-Fos, suggesting
      that the primary molecular defect in fibrodysplasia ossificans progressiva may be
      independent of the sustained Fos effects on chondrogenesis and osteogenesis.
      Comparisons of the clinical, molecular, and pathogenetic features of the c-Fos
      embryonic stem cell chimeras with those of fibrodysplasia ossificans progressiva
      provide insight into the earliest events in the molecular pathogenesis of
      genetically induced heterotopic chondrogenesis and osteogenesis. The relevance of
      the c-Fos embryonic stem cell chimera to the study of the currently untreatable
      human disease fibrodysplasia ossificans progressiva demonstrates the power of
      using embryonic stem cell technology for generating gain of function mutations in
      the study of human bone disease.

PMID- 9577415
TI  - Similarities in the phenotypic expression of pericytes and bone cells.
AB  - Bovine brain microvessel pericytes, bone cells, and fibroblasts were grown in
      tissue culture in 3%, 21%, or 60% oxygen for 7 weeks. Alkaline phosphatase
      activity was highest in bone cells and pericytes grown in 3% oxygen, with the
      activity higher in the former than the latter. Alkaline phosphatase activity was
      very low in fibroblasts at every oxygen concentration. Osteocalcin concentration
      was higher in bone cells than in pericytes, was not detected in fibroblasts, and
      in bone cells and pericytes the concentration was highest in 21% oxygen. Other
      bovine brain microvessel pericytes were grown in 3% or 21% oxygen for 3 to 24
      days in the presence or absence of bone morphogenetic protein 2 and in the
      presence or absence of parathyroid hormone. At Day 3 of culture, alkaline
      phosphatase activity was highest in 21% oxygen in the presence of bone
      morphogenetic protein 2. By Day 17 of culture, alkaline phosphatase activity was
      highest in 3% oxygen whether bone morphogenetic protein was present or not.
      Cyclic adenosine monophosphate production in pericytes in response to parathyroid
      hormone stimulation was very modest when compared with that of bone cells, and
      this response was not found to be significantly altered by bone morphogenetic
      protein 2, duration of culture, or the oxygen concentration during incubation.
      These findings show that the microvessel pericyte is capable of exhibiting
      several oxygen dependent, phenotypic characteristics ascribed to osteoblasts.

PMID- 9577416
TI  - Pulmonary and cardiac function in advanced fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva is a rare genetic disease characterized by
      heterotopic ossification in soft tissues. Severe disability results from
      progressive immobilization of the limbs, jaw, and chest wall. To determine
      whether cardiac function is altered in this disease, 25 patients ranging in age
      from 5 to 55 years (disease duration 1-51 years) were studied. History, physical
      examination, pulmonary functions, electrocardiography, and echocardiography were
      performed on each patient. Physical examination of the lungs and heart was
      unrevealing; no right sided ventricular gallops were heard, and no patient was
      found to have neck vein distention or peripheral edema. The patients had
      extremely limited chest expansion (1.9 +/- 0.8 inches), suggesting dependence on
      diaphragmatic breathing. Lung volumes were severely reduced (mean forced vital
      capacity 44% +/- 14% of predicted), but flow rates were relatively normal. All
      patients had normal capillary oxygen saturation. Echocardiography was technically
      difficult, but no abnormalities of left or right ventricular function were seen.
      Ten (40%) patients had electrocardiographic evidence of right ventricular
      dysfunction. Compared with patients without such evidence, these patients were
      older, had significantly longer disease duration, higher hemoglobin, and more
      impaired pulmonary function. The results of this study suggest that the presence
      of severely restrictive chest wall disease is associated with a high incidence of
      right ventricular abnormalities on electrocardiogram. Whether cor pulmonale will
      eventually occur remains to be determined.

PMID- 9577417
TI  - Catastrophic falls in patients who have fibrodysplasia ossificans progressiva.
AB  - There have been numerous anecdotal reports of catastrophic falls in patients with
      fibrodysplasia ossificans progressiva. To determine the incidence of serious
      morbidity and mortality associated with falls in this patient population, the
      authors surveyed the 135 patient members of the International Fibrodysplasia
      Ossificans Progressiva Association and an age and gender matched control group.
      Eighty-one percent of the fibrodysplasia ossificans progressiva population
      suffered a fall resulting in injury compared with 44% of the controls. Sixty
      seven percent of the falls initiated a painful flareup of fibrodysplasia
      ossificans progressiva leading to permanent loss of movement in almost all
      patients. Fifty-four percent of all falls suffered by the fibrodysplasia
      ossificans progressiva group led to permanent disability compared with 4% of all
      falls in the control group. Although trauma to the head was a common site of
      injury in both groups, the injury profile in the fibrodysplasia ossificans
      progressiva group included traumatic brain injuries, intracranial hemorrhage and
      death whereas the control group suffered mostly minor soft tissue lacerations.
      Deficiencies in coordinate gait and protective function likely accounted for the
      severity of injuries especially to the head in the fibrodysplasia ossificans
      progressiva population. Precautions are recommended that are intended to minimize
      the risk of injury without compromising a patient's functional level and
      independence. These recommendations include limitation of high risk activities,
      protective head gear, safety improvements in living environments, and
      augmentation of stabilizing and protective functions.

PMID- 9577418
TI  - Effects of intravenous etidronate and oral corticosteroids in fibrodysplasia
      ossificans progressiva.
AB  - There is no known effective therapy for fibrodysplasia ossificans progressiva.
      Ethane-1-hydroxy-1-diphosphonate has been studied because of its inhibitory
      effect on bone mineralization and its potential to impair the rapid ossification
      process observed after acute episodes of fibrodysplasia ossificans progressiva.
      In an open study, the effects of intravenously administered ethane-1-hydroxy-1
      diphosphonate and oral corticosteroids in the treatment of fibrodysplasia
      ossificans progressiva was evaluated. Thirty-one fibrodysplasia ossificans
      progressiva attacks were observed in seven patients during the mean followup of 6
      years. In 29 attacks, the authors observed a rapid diminution of local
      inflammation, swelling, and pain during the first 7 days of treatment. However,
      despite the ethane-1-hydroxy-1-diphosphonate treatment, 10 new ossifications were
      observed, causing severe deterioration of joint mobility in all affected
      patients. In 21 attacks, no new ectopic ossification appeared. The radiologic
      pattern of preexisting ossifications did not change during the treatment. There
      are no data in the literature describing the percentage of acute episodes leading
      to an ossification. The results suggest the possibility that intravenous
      administration of ethane-1-hydroxy-1-diphosphonate and oral steroids may be
      helpful for the treatment of fibrodysplasia ossificans progressiva, but more
      control data on the spontaneous resolution of early flareups are needed.

PMID- 9577419
TI  - Treatment of patients who have fibrodysplasia ossificans progressiva with
      isotretinoin.
AB  - Retinoids are a plausible family of therapeutic agents for fibrodysplasia
      ossificans progressiva due to their ability to inhibit differentiation of
      mesenchymal tissue into cartilage and bone. A prospective study was conducted to
      assess the efficacy of isotretinoin (13-cis-retinoic acid) in the prevention of
      heterotopic ossification in patients who had fibrodysplasia ossificans
      progressiva. Eleven anatomic regions were assessed in each of 21 patients by
      clinical examination, radiographs, and bone scans. An anatomic region was
      considered to be involved if there was clinical, radiographic, or radionuclide
      evidence of orthotopic or heterotopic ossification anywhere in the region. There
      were 143 involved anatomic regions and 88 uninvolved anatomic regions at the
      beginning of the study. Only one of the 88 anatomic regions that was completely
      uninvolved at the beginning of the study became involved during isotretinoin
      therapy. However, 16 of the 21 patients (76%) had major flare ups develop in 38
      of 143 (27%) previously involved anatomic regions while administered isotretinoin
      therapy. Isotretinoin at steady state doses of 1 to 2 mg/kg per day decreased the
      incidence of heterotopic ossification at uninvolved anatomic regions compared
      with an external control group, as long as the medication was started before the
      appearance of any orthotopic or heterotopic ossification in that anatomic region.
      The data did not allow the determination of whether isotretinoin was effective or
      detrimental in preventing disease flareups in regions that had even minimal
      orthotopic or heterotopic ossification at the time the therapy began. Extreme
      caution should be exercised when using this medication in patients who have
      fibrodysplasia ossificans progressiva.

PMID- 9577420
TI  - Mechanism for superior subluxation of the glenohumeral joint in fibrodysplasia
      ossificans progressiva.
AB  - Progressive heterotopic ossification leads to ankylosis of the major joints in
      patients who have fibrodysplasia ossificans progressiva. Joint subluxation has
      not been recognized widely in patients with this disease. The clinical records
      and radiographs of 79 patients with fibrodysplasia ossificans progressiva were
      reviewed and, it was found that humeral to chest wall synostosis and subluxation
      of the glenohumeral joint had occurred in 21% of skeletally immature patients and
      in 74% of skeletally mature patients. In fibrodysplasia ossificans progressiva,
      synostosis of the humeral shaft to the chest wall commonly occurs by 7 years of
      age, well before the age of proximal physeal closure. The continued growth of the
      proximal humeral physis in the presence of a humeral to chest wall synostosis
      causes the humeral head to migrate superiorly, thus promoting growth related
      subluxation. The clinical significance of this finding for patients who have
      fibrodysplasia ossificans progressiva is unknown, but this unique model will be
      useful in the study of shoulder biomechanics and growth plate physiology.

PMID- 9577421
TI  - Pseudomalignant heterotopic ossification.
AB  - Pseudomalignant heterotopic ossification is a rare, self limited connective
      tissue disorder of unknown origin that may occur atypically during childhood and
      can simulate either soft tissue sarcoma or fibrodysplasia ossificans progressiva.
      A complex constellation of diagnostic features usually enable the differentiation
      of pseudomalignant heterotopic ossification from extraosseous osteosarcoma and
      fibrodysplasia ossificans progressiva during a time span of approximately 8 to 12
      weeks. Orthopaedic surgeons who treat children with connective tissue tumors
      should be familiar with pseudomalignant heterotopic ossification and its
      differential diagnosis. The occasional mild and variable expression of
      fibrodysplasia ossificans progressiva rarely may make it more difficult to
      distinguish from pseudomalignant heterotopic ossification. It is possible that
      pseudomalignant heterotopic ossification is a form fruste of fibrodysplasia
      ossificans progressiva.

PMID- 9577422
TI  - Life expectancy and cost utility after total hip replacement.
AB  - In a prospective study of 410 cemented hip replacements in 372 patients with a
      mean age of 71 years, mortality after 8 years was 33%. Mortality for patients
      with osteoarthrosis was lower than in an age matched control population, probably
      because of a preoperative selection of patients. An estimate of costs and
      adjusted quality of life has shown that total hip replacement has a good cost
      utility even in the elderly patient. The conclusion of this study is that the
      indications for hip replacement in the elderly patient can be expanded. Such
      patients should undergo surgery earlier in the course of their disease.

PMID- 9577423
TI  - Outcome and prognostic factors of achilles rupture repair using a new scoring
      method.
AB  - A new clinical scoring system, including subjective assessment of symptoms and
      evaluation of ankle range of motion and isokinetic measurement of ankle plantar
      flexion and dorsiflexion strengths, is presented in 101 patients (86 men, 15
      women) who had repair of a closed Achilles tendon rupture. Twenty-one patients
      were competitive athletes and 70 were recreational athletes. Eighty-one percent
      of the ruptures were related to sports, and 32% occurred while playing
      volleyball. Twenty-six patients had previous Achilles tendon symptoms. At
      followup, an average of 3.1 years after repair, the overall result scores were
      excellent in 34 cases, good in 46, fair in 17, and poor in four. Only age was a
      predictor of overall results. The isokinetic strength scores were excellent or
      good in 72 cases, fair in 18, and poor in 11. Presence of systemic diseases,
      activity level, previous Achilles tendon symptoms, and later return to physical
      exercise were predictors of strength results. Gender, body weight, height, period
      between rupture and operation, surgeon, rupture site, operative method,
      complications, and thickness, width, and area of the Achilles tendon at followup
      were not related significantly to the outcome.

PMID- 9577424
TI  - Osteochondritis dissecans of the femoral condyle in the growth stage.
AB  - The site of lesion, spontaneous healing, onset mechanism, and magnetic resonance
      imaging findings of 51 knees in 38 patients with osteochondritis dissecans
      involving the femoral condyle in the growth stage were investigated. tercondylar
      site, and the remaining 1/4 were in other sites. Compared with those in the other
      sites, the lesions in a medial intercondylar site had a lower healing rate and
      required a longer time to heal. T2 weighted images of the lesions showed a
      progression from low signal areas to the appearance of a high signal line at the
      fragment to parent to bone interface, to a high signal double line at the
      interface and parent-bone surface, or to disappearance of the line. Magnetic
      resonance imaging often revealed discoid menisci or meniscal tears in patients
      with lesions in the lateral condyle, suggesting that endogenous forces play an
      important role in the onset of osteochondritis dissecans.

PMID- 9577425
TI  - Enhanced fixation with hydroxyapatite coated pins.
AB  - Three groups of seven patients had external fixation of middiaphyseal tibial
      fractures using uncoated pins, uncoated bicylindrical pins, and hydroxyapatite
      coated bicylindrical pins, respectively. All fractures were fixed with six pins,
      and all fractures united. Median pin insertion torque was 0.6, 1.2, and 1.3 Nm in
      the three groups, respectively. Median extraction torque was 0.1, 0.1, and 2.1
      Nm, respectively. Both types of stainless steel pins showed a lower extraction
      torque than insertion torque in all cases, whereas the mean extraction torque in
      the hydroxyapatite coated pins was unchanged. Seven of the 14 patients receiving
      uncoated pins had pin tract infection, compared with none of the patients
      receiving hydroxyapatite coated pins. Hydroxyapatite coating of external fixation
      pins increases stability and thereby reduces the risk for pin tract infection and
      mechanical failure of fracture fixation.

PMID- 9577427
TI  - Intraosseous tophaceous pseudotumor in the trigonal process of the talus.
AB  - Primary gout with destructive tophaceous pseudotumor development rarely occurs in
      juvenile patients with asymptomatic hyperuricemia. An expansile, intraosseous
      tophaceous pseudotumor on the posterior process of the talus was verified in a 14
      year-old boy with posterior ankle impingement and asymptomatic hyperuricemia. A
      review of the literature found no similar cases had been reported. The
      pathogenesis of this intraosseous tophaceous pseudotumor on the trigonal process
      probably was caused by the penetration of urate crystals from the periosteum into
      the posterior process of the talus. However, the time that this intraosseous
      tophaceous pseudotumor developed probably was close to the time that the second
      ossification center of the talus fused to the talus. Thus, it cannot be ruled out
      that the intraosseous tophaceous pseudotumor had formed during the fusion process
      of the second ossification center as a possible pathogenic mechanism in this
      unusual case.

PMID- 9577426
TI  - Neoadjuvant chemotherapy for high grade malignant fibrous histiocytoma of bone.
AB  - Between March 1983 and December 1994, 65 patients with malignant fibrous
      histiocytoma of bone in the extremities were treated with neoadjuvant
      chemotherapy administered according to four different regimens. A limb salvage
      was done in 58 patients (89%) and amputation in seven. The histologic response to
      preoperative chemotherapy was good (90% or more tumor necrosis) in 16 patients
      (25%) and poor in 49 (75%). At a median followup of 7 years (range, 2-13 years),
      40 patients (69%) remained continuously free of disease and 20 patients
      experienced relapse (18 with metastases and two with local recurrences followed
      by metastases). The rate of disease free survival was significantly higher for
      patients who had a good response than for those who had a poor response (94%
      versus 61%), although no significant differences in histologic response and
      disease free survival were seen with the four different regimens. These results
      show that a high percentage of patients with malignant fibrous histiocytoma of
      the extremities can be cured with neoadjuvant chemotherapy and that for most of
      them it is possible to avoid amputation.

PMID- 9577428
TI  - Immune responses and clinical outcome of massive human osteoarticular allografts.
AB  - Cell mediated immune responses as measured by lymphocyte proliferation induced by
      the mitogens phytohemagglutinin and concanavalin A and antigen extracts of donor
      derived bone were studied within 2 years after wide resection of bone tumors in
      18 patients receiving fresh frozen massive osteoarticular allografts. No uniform
      changes were seen in mitogen induced responses in 18 patients. However, five of
      nine patients tested with antigen extracts of donor derived bone showed elevated
      immune responses, one moderate and four weak. The incorporation of the allograft
      (evaluated by repeated radiographs; specific isotope techniques; clinical outcome
      assessed by the functional rating scores of Mankin-Waber and the Musculoskeletal
      Tumor Society; and histologic biopsy findings on new bone formation) did not
      differ in these patients from those in patients without any response to donor
      derived tissue. During a long term followup (mean, 11 years; range, 2-20 years),
      degenerative joint and sclerotic density bone changes developed after 2 to 4
      years without correlation to immune responses. Histologic specimens showed no
      signs of immunologic reaction, and no clinical rejection episodes were recorded.
      A slightly variable immune response to allograft bone seems to occur, but its
      clinical significance for outcome of the grafts remains to be determined. The low
      immune responses might reflect a low antigen release rate through an indirect
      pathway or immunologic tolerance to antigens or proteins shed from massive
      allografts that are nonliving scaffold implants during the creeping substitution
      process, corresponding to the low immune response and the slow histologic repair.

PMID- 9577429
TI  - Sporotrichal arthritis in south central Kansas.
AB  - Sporotrichal arthritis is a rare disease, with only 51 cases reported in the
      English literature. Thirteen patients with sporotrichal arthritis have been
      treated at Wichita area hospitals since 1979. Most of the patients were middle
      aged men. Significant alcohol intake was noted in 77% of the patients. There were
      17 joints involved in the cases, including 10 knees, three interphalangeal
      joints, one elbow, one midtarsal, one intercarpal, and one metatarsophalangeal
      joint. The typical appearance was an afebrile patient with a mildly swollen warm
      joint without erythema. The leukocyte counts were normal in 85% of patients, and
      the erythrocyte sedimentation rates were elevated in 100%. The patients had
      various treatments and responses. Response rates included intravenous
      amphotericin B (16%), ketoconazole (40%), and arthrodesis (100%). Sporotrichal
      arthritis may be more common than previously thought. It should be considered
      early in the differential diagnosis of monoarthritis.

PMID- 9577430
TI  - Reliability of closed double helix electrode for functional electrical
      stimulation.
AB  - The reliability of a closed double helix electrode in the lower limbs was
      studied. This electrode is an implanted intramuscular electrode and is used for a
      totally implantable functional electrical stimulation system. Eighty electrodes
      were evaluated retrospectively with a mean period of 15 months. The total implant
      time was 1222 electrode months. The cumulative proportion surviving was 0.934 at
      6 months, 0.855 at 1 year, 0.765 at 2 years, and 0.730 after 30 months. Fifteen
      of 80 electrodes failed, seven showed increasing electrode impedance, and eight
      had undesirable changes in recruitment. Of the failed electrodes, 2/3 failed
      during the first 10 months. The reliability was 0.91 at 6 months and 0.80 at 1
      year after implantation in all muscle groups. The closed double helix electrode
      displayed an increased reliability when compared with the open double helix
      electrode at 6 months, and an equivalent reliability as compared with the
      electrodes developed by Handa and colleagues at 6 months and 1 year, using the
      chi squared test for independence. This study suggests that the closed double
      helix electrode has an acceptable reliability and can be used as a part of a
      totally implantable functional electrical stimulation system.

PMID- 9577431
TI  - Reharvest of iliac crest donor site cancellous bone.
AB  - Patients requiring cancellous bone grafting of an extensive deficit or multiple
      bone grafting procedures often lack a sufficient quantity of autogenous
      cancellous bone. Canine studies have indicated that a potential exists for
      reharvesting autogenous cancellous bone from an iliac crest donor site using a
      trapdoor harvesting technique. However, significant human experience with this
      procedure has been lacking. This report describes four patients who underwent
      successful reharvesting of an iliac crest donor site that provided clinically
      sufficient autogenous cancellous bone graft material to treat an ongoing or a new
      skeletal problem. These patients all met specific criteria regarding use of the
      trapdoor method of bone graft harvest and a minimum 24-month interval between
      bone grafting procedures. Preoperative computed tomography scanning of the iliac
      crest was useful in documenting that sufficient cancellous bone was available for
      reharvest. It appears that iliac crest donor site reharvesting is a specific
      advantage of the trapdoor technique and is a possible alternative to multiple
      site grafting or the use of allograft or bone substitute materials.

PMID- 9577432
TI  - A quantitative study of articular repair in the guinea pig.
AB  - This study examined the healing of articular defects, with and without carbon
      fiber implants, and the response of repair tissue to its interim removal in
      guinea pigs of different ages. These were investigated after the induction of
      full thickness articular cartilage defects in the patellar groove of skeletally
      mature and immature guinea pigs. To indicate its capacity for replacement after
      attrition, repair tissue occurring in untreated (control) and carbon fiber
      treated (experimental) defects was ablated after 8 weeks, and the animals were
      sacrificed after an additional 8 weeks. The repair tissue was studied
      quantitatively at gross and microscopic levels and qualitatively using scanning
      and transmission electron microscopic study. The principal findings were as
      follows. The initial formation of repair tissue was variable, but it occurred in
      most cases. Secondary repair tissue formation consistently occurred after
      excision. Age did not influence the degree of repair. Carbon fiber implants of
      the type used impaired healing of small full thickness articular cartilage
      defects, compared with no treatment. Microscopically, repair tissue contains five
      main cell types, each with a characteristic surrounding matrix. Intermediate
      forms also are found. These, together with four of the five main types comprise a
      morphologic continuum and fit readily into a proposed developmental sequence that
      may stem from the fibroblast.

PMID- 9577433
TI  - Bacteria inhibit biosynthesis of bone matrix proteins in human osteoblasts.
AB  - The effect of extracts from Staphylococcus aureus and Staphylococcus epidermidis
      on bone matrix production were assessed by analyzing the biosynthesis of
      osteocalcin and Type I collagen in a human osteoblastic osteosarcoma cell line
      (MG-63). In MG-63 cells, extracts from Staphylococcus aureus and Staphylococcus
      epidermidis decreased 1,25(OH)2-vitamin D3 stimulated osteocalcin biosynthesis,
      and insulin-like growth factor I induced production of Type I collagen in a
      concentration dependent manner. The basal rate of osteocalcin and Type I collagen
      formation was unaffected by the bacterial extracts. The inhibitory effect of the
      bacteria on osteocalcin biosynthesis was seen after 24 hours of treatment and was
      maintained for at least 96 hours. The extracts of Staphylococcus aureus and
      Staphylococcus epidermidis enhanced prostaglandin E2 formation in the MG-63
      cells. Abolition of the prostaglandin E2 response by treatment with indomethacin
      and flurbiprofen did not affect bacteria induced inhibition of osteocalcin
      production. Stimulation of osteocalcin biosynthesis by 1,25(OH)2-vitamin D3 was
      associated with a decreased rate of cell proliferation. The inhibitory action of
      the bacterial extracts was not linked to any inhibition of [3H]-thymidine
      incorporation into deoxyribonucleic acid. These data show that extracts of
      Staphylococcus aureus and Staphylococcus epidermidis have the ability to inhibit
      the biosynthesis of bone matrix proteins by a nonprostaglandin and noncytotoxic
      dependent mechanism and suggest that bone loss in inflammatory processes
      containing Staphylococcus aureus or Staphylococcus epidermidis may not be caused
      only by enhanced bone resorption but also by decreased bone formation.

PMID- 9577434
TI  - Benzalkonium chloride. A potential disinfecting irrigation solution for
      orthopaedic wounds.
AB  - The efficacy of benzalkonium chloride was evaluated as an irrigating solution for
      the eradication of Staphylococcus aureus from a contaminated orthopaedic wound.
      Thirty Sprague Dawley rats were randomized into two groups. A stainless steel
      wire was placed in a lumbar spinous process, and the wound was inoculated with
      10(7) or 10(6) colony forming units of Staphylococcus aureus. The wound was
      irrigated with 1 L of normal saline or 0.1% benzalkonium chloride solution. The
      animals were sacrificed, and cultures were obtained. Rats inoculated with 10(7)
      colony forming units of Staphylococcus aureus and irrigated with benzalkonium
      chloride had a significant decrease in the total number of positive cultures,
      deep wound cultures, and stainless steel wire cultures. Rats inoculated with
      10(6) colony forming units of Staphylococcus aureus and irrigated with
      benzalkonium chloride also had a significant decrease in the total number of
      positive cultures, deep wound cultures, and stainless steel wire cultures. In a
      parallel noninoculation study, histologic evaluation of tissues did not show
      toxicity in the rats irrigated with benzalkonium chloride. This study shows that
      benzalkonium chloride is more effective than normal saline as an irrigating agent
      for eradicating Staphylococcus aureus from a contaminated orthopaedic wound.

PMID- 9577435
TI  - Magnetic resonance imaging of the musculoskeletal system: the spine.
AB  - Magnetic resonance imaging in the patient who has had surgery is discussed. The
      most common indication for postoperative imaging is in the distinction between
      postoperative fibrosis and recurrent disc herniation. Magnetic resonance imaging
      is invaluable in the assessment of potential causes of failed back surgery
      syndrome such as postoperative infection, arachnoiditis and adjacent segment
      degeneration. Magnetic resonance imaging assumes a less important role in
      postoperative patients with metal hardware owing to image degradation secondary
      to metal artifact. Magnetic resonance imaging has a complementary role with
      computed tomography evaluation of spinal trauma. It excels at the noninvasive
      evaluation of spinal deformities and neoplasms.

PMID- 9577436
TI  - Sclerosis and swelling of the clavicle in a 44-year-old woman.

PMID- 9577437
TI  - Postoperative outcome related to preoperative symptomatology.

PMID- 9577438
TI  - Primary pulmonary hypertension: new reasons for optimism?

PMID- 9577439
TI  - Prescriptions, practitioners and pharmacists.

PMID- 9577440
TI  - Medical informatics meets medical education.

PMID- 9577441
TI  - Attitudes to and use of a modified prescription form by general practitioners and
      pharmacists.
AB  - OBJECTIVE: To evaluate the rate of use and acceptance of a new prescription form
      designed to provide more information to pharmacists and patients. DESIGN:
      Prospective descriptive study. SETTING: A semi-rural community outside Melbourne,
      Victoria, in November 1994. PARTICIPANTS: GPs and pharmacists working three or
      more sessions per week in the locality, and 21 consumers who formed two consumer
      focus groups. INTERVENTION: An education session for GPs and pharmacists,
      followed by a one-month trial of new prescription forms which included notations
      to facilitate interprofessional communication. MAIN OUTCOME MEASURES: Rate of use
      and acceptability of the new prescription notations. RESULTS: Eighteen GPs and 10
      pharmacists participated; 3600 forms were issued and 2521 prescriptions,
      including 3464 prescription items, were analysed. GPs and pharmacists used at
      least one of the new prescription notations in 45% (1559) of prescription items;
      35% of prescription items (1222) were notated with the general purpose of the
      medication. Qualitative findings suggested that GPs, pharmacists and consumers
      considered the new prescription form to be beneficial and useful. CONCLUSIONS: A
      modified prescription form to increase communication between GPs and pharmacists
      is acceptable in clinical practice.

PMID- 9577442
TI  - The shady side of solar protection.
AB  - OBJECTIVE: To determine the value of shade in protecting humans from solar
      ultraviolet (UV) radiation. DESIGN AND SETTING: Measurement with photometers of
      protection factors for ultraviolet B radiation (UVB) and for total solar
      radiation for different types of trees and other structures during the summer
      months (1995-1997) in south-east Queensland. (The protection ratio is the ratio
      of the intensity of UVB or total solar radiation in direct sunlight to that in
      shade.) RESULTS: For summer sun at midday, the mean (SD) UV protection ratio for
      the shade of trees (n = 65) was 4.21 (1.36) on a horizontal surface and 1.33
      (0.30) on a vertical surface. In contrast, the mean (SD) protection ratio for
      total solar energy (primarily infrared) was much higher (12.1 [1.4]). Trees
      common in recreational areas in Australia (eucalypts: UV protection ratio, 3.52
      [0.79]; Norfolk Island pines: UV protection ratio, 3.72 [0.98]) offered reduced
      protection compared with trees with more dense foliage (UV protection ratio, 5.48
      [1.44]). Over a whole day, measurement of shade by trees and other structures
      showed that the UV protection ratio was lower in the morning and afternoon. Shade
      from awnings, buildings and hats gave similar results to those for trees. Both at
      midday and over a whole day satisfactory protection (UV protection ratio > 15)
      was obtained only in shade which eliminated exposure to the sky as well as to
      direct sunlight; for example, in thickly wooded areas and under low, widely
      overhanging structures. CONCLUSIONS: Most forms of shade, while useful, offer
      people insufficient protection from solar UV. A fair-skinned person sheltering
      under a tree could suffer sunburn after less than one hour. There is a need for
      appropriate design of structural shade, use of other solar protection measures in
      conjunction with shade, and research on behavioural responses to shade.

PMID- 9577443
TI  - Colorectal cancer screening by general practitioners: comparison with national
      guidelines.
AB  - OBJECTIVE: To determine whether general practitioners (GPs) had received
      Australian guidelines on early detection, screening and surveillance for
      colorectal cancer or rectal bleeding, and whether their reported practice
      conformed with these guidelines. DESIGN: Cross-sectional postal survey of self
      reported practice. PARTICIPANTS AND SETTING: 213 GPs in practice in the southern
      metropolitan area of Perth, Western Australia, were randomly selected from the
      Fremantle Regional Division of General Practice database and surveyed in March
      1997. RESULTS: Replies were received from 155 (73%) of the GPs, and 110 reported
      receiving guidelines (from the Australian Gastroenterology Institute [AGI], 44;
      Gut Foundation of Australia [GFA], 40; others, 6; and not specified, 20). GPs who
      reported receiving guidelines were significantly more likely to screen for
      colorectal cancer (99/110; 90%) than those who reported not receiving guidelines
      (33/45; 73%) (P = 0.008). The commonest method to investigate people with
      identifiable risk factors for colorectal cancer was colonoscopy. Reported
      screening frequencies in asymptomatic patients with above-average risk (family
      history of colorectal cancer or past history of adenomatous polyps or colorectal
      cancer) were significantly higher than recommended by AGI and GFA guidelines (P <
      0.05). Up to 24% of GPs investigated altered bowel habit or bleeding per rectum
      with faecal occult blood testing. CONCLUSIONS: Most GPs report having received
      guidelines. Reported screening frequency was higher than recommended for most
      above-average-risk patients, which will result in excessive consumption of
      resources without benefits for cancer prevention.

PMID- 9577444
TI  - Chromobacterium violaceum in tropical northern Australia.
AB  - Chromobacterium violaceum is an unusual cause of infection which may have
      fatality rates of over 60% when systemic illness occurs. We describe four
      patients infected with this organism who were successfully treated at Royal
      Darwin Hospital between 1991 and 1996. In tropical Australia, C. violaceum
      infection should be considered along with melioidosis in patients who present
      with a septic illness with skin lesions and/or organ abscesses after exposure to
      soil in the wet season.

PMID- 9577445
TI  - Healthcare and the information age: implications for medical education.
AB  - The information age, combining rapidly developing information technology and
      massive growth in biomedical and clinical data, is placing special demands on
      healthcare workers. Further, radical changes in access to information in our
      society are affecting the doctor-patient relationship. These changes necessitate
      a new approach to primary and continuing medical education. A number of
      imperatives for medical education are identified and some practical changes to a
      medical curriculum are described.

PMID- 9577446
TI  - Should third-generation cephalosporins be the empirical treatment of choice for
      severe community-acquired pneumonia in adults?
AB  - The choice of empirical treatment for community-acquired pneumonia (CAP) is
      highly controversial. Our survey of 42 Australian emergency department doctors
      showed that monotherapy with a third-generation cephalosporin was the preferred
      regimen for severe CAP (14/42; 33%). We argue that cheaper regimens with a
      narrower spectrum are likely to be just as effective as third-generation
      cephalosporins and will have fewer adverse effects on the microbial ecology of
      hospitals. We suggest penicillin or ampicillin (to cover pneumococci--even if
      penicillin "resistant"--and Haemophilus influenzae), plus a macrolide (e.g.,
      azithromycin or erythromycin; to cover Legionella and other "atypical"
      pathogens), plus a single large dose of an aminoglycoside (e.g., gentamicin; to
      cover gram-negative bacilli such as Klebsiella pneumoniae) as empirical therapy
      for severe CAP.

PMID- 9577447
TI  - Rediscovering vascular surgery: of arterial injury and amputation.

PMID- 9577448
TI  - Alcohol and drug dependence: diagnosis and management.

PMID- 9577449
TI  - Don't forget the hepatitis A vaccine.

PMID- 9577450
TI  - Increasing ampicillin resistance among non-invasive Haemophilus influenzae
      isolates.

PMID- 9577451
TI  - Recurrent Haemophilus influenzae type b infection--a case report.

PMID- 9577452
TI  - Maintenance of the vaccine cold chain by councils and general practices in
      Victoria.

PMID- 9577453
TI  - Inactivation of HIV in factor VIII.

PMID- 9577455
TI  - Acceptance of clinical practice guidelines.

PMID- 9577454
TI  - Nitrogen dioxide, gas heating and respiratory illness.

PMID- 9577456
TI  - Assessment of anxiety and depression in primary care.

PMID- 9577457
TI  - No more "publish or perish".

PMID- 9577458
TI  - Antibiotic-resistant pneumococci.

PMID- 9577459
TI  - The nutritional health of New Zealand vegetarian and non-vegetarian Seventh-day
      Adventists: selected vitamin, mineral and lipid levels.
AB  - AIM: To determine whether adult non-vegetarian Seventh-day Adventists differ in
      selected nutrition related health aspects from adult vegetarian Seventh-day
      Adventists. METHODS: One hundred and forty-one Seventh-day Adventist church
      members responded to a general health questionnaire. Forty-seven sex and age
      matched subjects (23 non-vegetarians and 24 vegetarians) were selected for
      further investigation. Blood lipids, serum vitamin B12, folate, haemoglobin and
      ferritin levels were measured along with stature, weight and blood pressure. A
      quantitative 7-day diet record was also completed. RESULTS: Body mass index was
      similar between the non-vegetarian and vegetarian groups but diastolic blood
      pressure was higher for non-vegetarian than vegetarian males. Even though the
      dietary vitamin B12 intake was significantly lower (p < 0.01) in the vegetarian
      group both vegetarians and non-vegetarians recorded similar serum vitamin B12
      levels. The vegetarian and non-vegetarian groups had similar haemoglobin
      concentrations. While dietary iron intake was higher in the female vegetarian
      group, though predominantly in the non-haem form, the difference was not
      significant. Low serum ferritin levels were found in both female dietary groups
      even though the vegetarian group had a significantly (p < 0.05) higher vitamin C
      intake. Blood lipid levels were similar in the two diet groups even though the
      vegetarian group had a lower percentage energy contribution from total and
      saturated fat (p < 0.01) and consumed significantly less cholesterol. CONCLUSION:
      Both non-vegetarian and vegetarian Seventh-day Adventists appear likely to enjoy
      a lower risk of nutrition related chronic degenerative disease than the average
      New Zealander and have a satisfactory iron and vitamin B12 status.

PMID- 9577460
TI  - Recommendations for cervical screening 1997. Members of the Working Party on
      Cervical Screening.
AB  - The Ministry of Health and the Cancer Society of New Zealand invited a working
      group to review the 1991 recommendations on cervical screening. No major changes
      have been suggested but minor modifications have been made with regard to recent
      literature. All women who have ever had intercourse should be offered a three
      yearly cervical smear test from age 20 to age 69. If it is a woman's first smear
      or there is a gap of five or more years since her last one, the second smear
      should be taken in one year's time. Women who have had a hysterectomy for a
      benign condition, with complete removal of histologically normal cervical
      epithelium and a normal smear history, do not require further screening. Women
      who are immunocompromised may require more frequent screening. The cervical smear
      will be part of the investigation of women with signs and symptoms of cervical
      cancer. It is not sufficiently sensitive, however, for a negative result to
      override clinical concern. Such women should be referred for gynaecological
      assessment irrespective of the smear result.

PMID- 9577461
TI  - Mild head injury in New Zealand: incidence of injury and persisting symptoms.
AB  - AIMS: To define mild head injury and determine its incidence and that of
      persisting symptoms. METHODS: Analysis of an eight week sample of all patients
      with head injury passing through the Emergency Departments of the four Auckland
      Hospitals, and of a five year sample of patients attending a clinic for
      management of symptoms persisting after head injury. RESULTS: Mild head injury
      was defined by the acute management needed--care out of hospital or not more than
      48 hours admission, corresponding reasonably with a definition using post
      traumatic amnesia. Incidence in those seen at hospital was 437/10(5) whole
      population/year for ages 15 and over, and 252/10(5) for ages under 15. Age
      specific incidences were 1769/10(5)/year for 15 and over, and 2920/10(5) for ages
      under 15, the major causes being road accidents (RTA) and falls, respectively.
      For 100 cases seen at hospital approximately 60 were treated by general
      practitioners alone. Referrals in patients 15 years and over because of
      persisting symptoms occurred in 5% (95%, CI 3-7), 69% in the first four months
      and 6% after a year. Referrals were equally likely after RTA, sports injuries and
      assaults, more frequent after objects striking the head. Older people were
      marginally more likely to be referred and the probability was significantly
      greater in women injured in sport and in minor RTA not needing admission to
      hospital. CONCLUSIONS: Mild head injuries are economically important and deserve
      efficient management.

PMID- 9577462
TI  - Cigarette smoking by New Zealand doctors and nurses: results from the 1996
      population census.
AB  - AIM: To determine the prevalence of cigarette smoking among New Zealand doctors
      and nurses and to examine intercensal trends in smoking behaviour. METHODS: The
      1996 New Zealand population census included two questions on cigarette smoking.
      The data for doctors and nurses have been analysed and compared with results from
      the 1976 and 1981 censuses. RESULTS: There were 7335 doctor respondents and
      30,507 nurses. Five percent of male and female doctors smoke cigarettes regularly
      compared with 15% in 1981, 20% in 1976 and 35% in 1963. Almost 90% of doctors
      aged less than 30 years have never smoked and reductions in smoking have occurred
      in all specialties. Eighteen percent of nurses (18% females, 27% males) are
      smokers compared with 31% of females and 39% of males in 1981. The highest
      prevalence is among psychiatric nurses (31%) while only 10% of midwives and
      Plunket nurses are smokers. CONCLUSIONS: Doctors continue to lead the New Zealand
      community in non-smoking and the goal of a smokefree medical profession by the
      year 2000 may be achievable. In contrast to 1981, the prevalence of smoking by
      female nurses (18%) is now less than women in the general New Zealand population
      (23%). Substantial reductions in smoking have occurred in all categories of the
      nursing profession.

PMID- 9577463
TI  - Humane medicine and literature.

PMID- 9577464
TI  - Youth suicide rates.

PMID- 9577465
TI  - Caesarean section rate.

PMID- 9577467
TI  - Renal abuse from non-steroidal, anti-inflammatory agents in sport.

PMID- 9577466
TI  - Attitudes to competition and advertising.

PMID- 9577468
TI  - The RSNA, radiology, and the last days of the century. Through red-colored
      goggles.

PMID- 9577469
TI  - The International Society for Magnetic Resonance in Medicine. Research directions
      in MR imaging.

PMID- 9577470
TI  - Commentary on the message from the International Society for Magnetic Resonance
      in Medicine.

PMID- 9577471
TI  - Uroradiology of the past, genitourinary and abdominal radiology of the future.

PMID- 9577472
TI  - Differentiation of benign versus pathologic compression fractures with diffusion
      weighted MR imaging: a closer step toward the "holy grail" of tissue
      characterization?

PMID- 9577474
TI  - The gastrointestinal tract: dos and don'ts of digital imaging.

PMID- 9577473
TI  - Urolithiasis: detection and management with unenhanced spiral CT--a urologic
      perspective.

PMID- 9577475
TI  - Multiplanar CT pancreatography and distal cholangiography with minimum intensity
      projections.
AB  - PURPOSE: To develop a technique of projectional computed tomographic (CT)
      cholangiopancreatography (CTCP). MATERIALS AND METHODS: Sixty-one patients
      underwent CT for suspected biliary or pancreatic abnormalities. The axial CT and
      CTCP techniques included spiral scanning during the portal venous phase and thick
      slab minimum intensity projections. Visualization of pancreatic and extrahepatic
      bile ducts (divided in five duct segments per patient) was graded blindly on a
      scale of 1-5 by a consensus of two radiologists. Two hundred seventy-seven duct
      segments were used to compare axial CT and CTCP in the depiction of duct segments
      and dilatation; 109 segments were used to compare CTCP with ERCP. RESULTS: Fifty
      six of 277 duct segments were not visualized on axial CT images; 15 segments were
      not visualized on CTCP images (P < .001). There was no statistically significant
      difference between the number of segments missed with ERCP and the number missed
      with CTCP: nine and three of 109 segments, respectively. Duct visualization was
      equal on axial CT and CTCP images in 35 of 109 duct segments and was superior on
      CTCP images in all but one of the remaining segments (P < .001). Duct
      visualization on CTCP images was equal to that on ERCP images in 35 segments,
      superior in nine, and significantly inferior in 66 (P < .001). CONCLUSION: CTCP
      improves CT depiction of pancreatic and bile ducts with a quality that approaches
      that of ERCP.

PMID- 9577476
TI  - Hyperechoic liver nodules: characterization with proton fat-water chemical shift
      MR imaging.
AB  - PURPOSE: To evaluate proton fat-water chemical shift fast low-angle shot magnetic
      resonance (MR) imaging for differentiation of fat-containing hyperechoic liver
      nodules from hyperechoic liver nodules without a fatty component. MATERIALS AND
      METHODS: T1-weighted fast low-angle shot fat-water chemical shift gradient-echo
      MR imaging was performed in 96 patients without cirrhosis with 138 hyperechoic
      liver nodules. In-phase and opposed-phase breath-hold images were acquired. The
      percentage of signal intensity variation between in-phase and opposed-phase
      images and the spleen-to-lesion contrast ratio were used to differentiate liver
      nodules. RESULTS: Chemical shift MR images showed fat in 15 (11%) hyperechoic
      nodules (two angiomyolipomas and 13 nodular fatty infiltrations of the liver).
      The mean percentage of signal intensity variation between in-phase and opposed
      phase images was 156% (standard error, 43.5%) in nodules with fat and -0.16%
      (standard error, 0.96%) in nodules without fat (P = .003). Spleen-to-lesion
      contrast was similar on in- and opposed-phase images in lesions without fat (mean
      difference, -0.0107; standard error, 0.012), whereas the mean difference in fat
      containing nodules was 0.805 (standard error, 0.225; P = .003). The area under
      the receiver operating characteristic curve was 0.97 for signal intensity
      variation. CONCLUSION: Hyperechogenicity in certain liver nodules is caused by
      fat. Chemical shift MR imaging allows accurate differentiation between these and
      other hyperechoic lesions with no fat component.

PMID- 9577477
TI  - MR imaging of the liver: comparison between single-shot echo-planar and half
      Fourier rapid acquisition with relaxation enhancement sequences.
AB  - PURPOSE: To evaluate single-shot T2-weighted magnetic resonance sequences and
      their role in clinical practice in patients with hepatic lesions. MATERIALS AND
      METHODS: Prospective comparison of echo-planar and half-Fourier rapid acquisition
      with relaxation enhancement (RARE) imaging was performed in 80 patients with
      focal hepatic lesions. Spin-echo (SE) single-shot echo-planar (echo times, 47 and
      80 msec) and half-Fourier RARE (echo time, 59 msec) images were compared with
      turbo SE (repetition time msec/echo time msec = 3,200-7,600/90) images.
      Quantitative, qualitative, and receiver operating characteristic (ROC) analyses
      were performed. RESULTS: For liver, signal-to-noise ratios on half-Fourier RARE
      images were significantly higher than those on echo-planar images (P < .01). For
      cystic lesions, contrast on half-Fourier RARE and echo-planar images was slightly
      higher than that on turbo SE images. For solid lesions, contrast on echo-planar
      images was better than that on half-Fourier RARE or turbo SE images. Artifacts
      including ghosting, bowel motion, susceptibility difference, and chemical shift
      were negligible on half-Fourier RARE images in all patients, whereas
      susceptibility difference and chemical shift of various degrees were seen on all
      echo-planar images. On the basis of ROC analyses, tumor detection rates were
      significantly higher with half-Fourier RARE and turbo SE images than with echo
      planar images (P < .01). CONCLUSION: Echo-planar images provide sufficient
      contrast to allow detection of both solid and cystic masses, but severe artifacts
      preclude routine use. Half-Fourier RARE images are free from artifacts (chemical
      shift and susceptibility) and diagnostic performance with them is similar to that
      with turbo SE images.

PMID- 9577478
TI  - Prolongation and optimization of Doppler enhancement with a microbubble US
      contrast agent by using continuous infusion: preliminary experience.
AB  - PURPOSE: To investigate whether continuous infusion of an echo-enhancing contrast
      agent for up to 15 minutes can provide uniform and prolonged enhancement.
      MATERIALS AND METHODS: Six volunteers each received one bolus and three infusions
      of a microbubble contrast agent over 6-15 minutes at (a) a standard rate (mean,
      2.08 mL/min), (b) a fast rate at twice the standard rate, and (c) a slow rate at
      half the standard rate. Spectral Doppler intensitometry of the femoral artery was
      performed for all infusions. Spectral Doppler ultrasound (US) scans of the
      femoral artery and color Doppler US scans of the carotid artery were subjectively
      assessed. RESULTS: All infusions provided an equilibrium plateau of constant
      prolonged enhancement starting after 1-2 minutes and lasting until the end of the
      infusion. Enhancement at the plateau was +13 dB (slow rate), +17.1 dB (standard
      rate), and +18.3 dB (fast rate) compared with baseline. Saturation artifacts with
      infusions were markedly fewer than those with bolus injections. Dose
      effectiveness (duration of enhancement that measured at least 7.5 dB per gram of
      contrast agent) was markedly improved with the infusions, from 0.8 min/g for the
      bolus to 2.6 min/g for the slow infusion. CONCLUSION: Continuous infusion of the
      microbubble contrast agent provided prolonged and uniform enhancement of Doppler
      signals and improved image quality by minimizing saturation artifacts.

PMID- 9577480
TI  - Anterolateral impingement of the ankle: effectiveness of MR imaging.
AB  - PURPOSE: To determine the effectiveness of magnetic resonance (MR) imaging in the
      diagnosis of anterolateral impingement of the ankle. MATERIALS AND METHODS: MR
      images were reviewed in 12 patients (12 ankles) with arthroscopically proved
      anterolateral impingement and in 19 control subjects (20 ankles) with diagnoses
      other than impingement. MR images were scored by means of consensus of two
      musculoskeletal radiologists and independently by a third radiologist. Patients
      underwent imaging at 1.5 T, with use of standard imaging sequences and a
      dedicated extremity coil. RESULTS: For the consensus reading, the sensitivity,
      specificity, and accuracy of MR imaging for the diagnosis of impingement were
      42%, 85%, and 69%, respectively. The frequency of lateral gutter fullness and
      anterior talofibular ligament thickening on MR images was higher in the 12 ankles
      with impingement (seven [58%] and seven [58%] ankles, respectively) than in the
      20 control ankles (seven [35%] and five [25%] ankles, respectively), but these
      trends did not reach statistical significance. Interobserver agreement for
      anterior talofibular ligament thickening was high, whereas that for lateral
      gutter fullness was fair. CONCLUSION: Conventional MR imaging of the ankle is
      insensitive for anterolateral impingement. Anterior talofibular ligament
      thickening and soft-tissue fullness in the lateral gutter may be suggestive of
      the diagnosis, but the reliability of the latter finding is questionable.

PMID- 9577479
TI  - Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus
      pathologic compression fractures.
AB  - PURPOSE: To evaluate the usefulness of diffusion-weighted magnetic resonance (MR)
      imaging of bone marrow for differentiating between benign and pathologic
      vertebral compression fractures. MATERIALS AND METHODS: Thirty patients with 39
      vertebral compression fractures were examined with MR imaging. Diffusion-weighted
      MR imaging was performed with a steady-state free precession sequence in 22 acute
      benign osteoporotic and/or traumatic fractures and 17 pathologic compression
      fractures. Biplanar radiographs, T1-weighted spin-echo (SE) MR images, and short
      inversion time inversion-recovery (STIR) MR images were available for all
      patients. The signal intensity characteristics were analyzed qualitatively and
      quantitatively (bone marrow contrast ratios and signal-to-noise ratios) for all
      sequences. RESULTS: At diffusion-weighted MR imaging, all benign vertebral
      compression fractures were hypo- to isointense to adjacent normal vertebral
      bodies. Pathologic compression fractures were hyperintense to normal vertebral
      bodies. Benign vertebral fractures had negative bone marrow contrast ratios at
      diffusion-weighted imaging, whereas pathologic vertebral fractures had positive
      values (P < .001). The difference in bone marrow contrast ratios for benign and
      pathologic compression fractures at T1-weighted SE and STIR imaging was not
      significant (P > .01). CONCLUSION: Diffusion-weighted MR imaging provided
      excellent distinction between pathologic and benign vertebral compression
      fractures.

PMID- 9577481
TI  - Hypertrophied palmaris longus muscle, a pseudomass of the forearm: MR appearance-
      case report and review of the literature.
AB  - Magnetic resonance (MR) imaging of the forearm was performed to evaluate a
      presumed forearm soft-tissue tumor in a 26-year-old man. Sagittal and axial
      images revealed a mass isointense to muscle just medial to the flexor carpi
      radialis tendon (in the expected location of the palmaris longus muscle). A
      diagnosis of hypertrophied palmaris longus muscle was made. The radiologist must
      be familiar with the MR imaging appearance of normal variants of the palmaris
      longus muscle, as this can obviate surgery.

PMID- 9577482
TI  - Unenhanced helical CT criteria to differentiate distal ureteral calculi from
      pelvic phleboliths.
AB  - PURPOSE: To identify imaging features at unenhanced helical computed tomography
      (CT) that help differentiate distal ureteral calculi from pelvic phleboliths.
      MATERIALS AND METHODS: Retrospective analysis was performed of 184 pelvic
      calcifications identified at unenhanced helical CT in 113 patients. The size,
      shape, and attenuation of each calcification were recorded in addition to the
      presence of a central lucency and the appearance of the adjacent soft tissues.
      With profile analysis, a graphic representation was generated of attenuation in
      each pixel along a line drawn through each calcification. RESULTS: Geometric
      configuration was seen in eight (21%) calculi but not in any phleboliths.
      Differences were significant (P < .0001) between the mean attenuation of calculi
      and that of phleboliths. Among phleboliths, none had a mean attenuation greater
      than 278 HU, 13 (9%) had a visible central lucency, 31 (21%) had a bifid peak at
      profile analysis, 30 (21%) had the "comet sign" (adjacent eccentric, tapering
      soft-tissue mass corresponding to the noncalcified portion of a pelvic vein), and
      three (2%) had the soft-tissue rim sign (edema of the ureteral wall). Among
      calculi, none had a central lucency, bifid peak, or comet sign, but 29 (76%) had
      the soft-tissue rim sign. CONCLUSION: Analysis of pelvic calcifications at
      unenhanced helical CT can help differentiate calculi from phleboliths.

PMID- 9577483
TI  - Adrenal adenomas and nonadenomas: assessment of washout at delayed contrast
      enhanced CT.
AB  - PURPOSE: To measure the changes in wash-in and washout of contrast material on
      contrast material-enhanced computed tomographic (CT) scans in patients with
      adrenal adenomas and nonadenomas. MATERIALS AND METHODS: One hundred twenty-two
      patients with 135 adrenal masses (74 adenomas, 61 nonadenomas) underwent helical
      CT. Unenhanced CT was followed by enhanced CT at 30, 60, and 90 seconds and 3,
      10, and 30 minutes. RESULTS: The adenomas enhanced significantly more than the
      nonadenomas at 60 seconds (P < .001), but the percentage enhancement of the
      adenomas was significantly greater than that of the nonadenomas at 30, 60, and 90
      seconds (P < .001). At 3, 10, and 30 minutes, the absolute percentage loss of
      enhancement and the relative percentage loss of enhancement were significantly
      greater for the adenomas than for the nonadenomas (P < .001). Delayed enhanced CT
      at 10 minutes (sensitivity, 92%; specificity, 95%) and 30 minutes (sensitivity,
      97%; specificity, 100%) was more accurate for differentiation of adenomas and
      nonadenomas than unenhanced CT (sensitivity, 82%; specificity, 95%). CONCLUSION:
      Adrenal adenomas exhibit greater washout of contrast material than do adrenal
      nonadenomas. The percentage change in washout of contrast material is a useful
      adjunct to absolute CT attenuation values in differentiation of adrenal adenomas
      and nonadenomas.

PMID- 9577484
TI  - Childhood pyelonephritis: comparison of gadolinium-enhanced MR imaging and renal
      cortical scintigraphy for diagnosis.
AB  - PURPOSE: To compare gadolinium-enhanced inversion-recovery magnetic resonance
      (MR) imaging with renal cortical scintigraphy in the diagnosis of childhood
      pyelonephritis. MATERIALS AND METHODS: Thirty-seven patients with fever-producing
      urinary tract infection underwent gadolinium-enhanced inversion-recovery MR
      imaging and technetium-99m renal cortical scintigraphy. Each study was read in
      double-blind fashion by two radiologists. The kidney was divided into three
      zones, and each was graded as positive, equivocal, or negative for
      pyelonephritis. RESULTS: Seventy kidneys (210 zones) were imaged. Twenty-six
      kidneys (54 zones) had evidence of pyelonephritis at both MR imaging and
      scintigraphy. Twenty-four kidneys (100 zones) were negative on both studies.
      Twelve kidneys (42 zones) were positive at MR imaging but negative at
      scintigraphy, and four kidneys (seven zones) were negative at MR imaging but
      positive at scintigraphy. The results of MR imaging for pyelonephritis were not
      equivalent to the results of scintigraphy (P = .001 for renal zones). The
      proportion of positive agreement between readers for the presence of
      pyelonephritis was 0.85 and 0.57 for MR imaging and scintigraphy, respectively.
      The proportion of negative agreement was 0.88 and 0.80 for MR imaging and
      scintigraphy, respectively. CONCLUSION: Gadolinium-enhanced inversion-recovery MR
      imaging enabled detection of more pyelonephritic lesions than did renal cortical
      scintigraphy and had superior interobserver agreement.

PMID- 9577485
TI  - Perirolandic cortex in infants: signal intensity on MR images as a landmark of
      the sensorimotor cortex.
AB  - PURPOSE: To correlate the perirolandic low signal intensity seen on T2-weighted
      magnetic resonance (MR) images in neonates and infants with the anatomically
      located sensorimotor cortex. MATERIALS AND METHODS: Axial T2-weighted MR images
      of 146 consecutive patients less than 6 months old were reviewed. The
      sensorimotor cortex was located by identifying the central sulcus. Two
      independent readers attempted to identify the central sulcus using two anatomic
      methods independently and in combination. The location of the central sulcus was
      compared with that of the perirolandic low signal intensity. RESULTS: Seventy-two
      normal hemispheres in 36 patients and 91 abnormal hemispheres in 47 patients
      showed clear perirolandic low signal intensity. The central sulcus was located
      anatomically in 70 and 72 normal hemispheres (97% and 100%, respectively) and 90
      and 91 abnormal hemispheres (99% and 100%, respectively). In all normal
      hemispheres, the identified central sulcus correlated with the perirolandic low
      signal intensity. In contrast, an apparent mismatch was found in two hemispheres
      in a patient with Dandy-Walker syndrome. CONCLUSION: The perirolandic low signal
      intensity seen on T2-weighted MR images is located exactly in the anatomic
      sensorimotor cortex in normal brains, whereas a mismatch can occur in abnormal
      brains.

PMID- 9577486
TI  - Lumbar spine: quantitative and qualitative assessment of positional (upright
      flexion and extension) MR imaging and myelography.
AB  - PURPOSE: To compare measurements of the sagittal diameter of the lumbar dural sac
      obtained at positional magnetic resonance (MR) imaging and at functional
      myelography and to assess the influence of various body positions on the dural
      sac and the intervertebral foramina. MATERIALS AND METHODS: Thirty consecutive
      patients referred for lumbar myelography were examined with an open 0.5-T MR
      imager, Sagittal T2-weighted fast spin-echo images were acquired with patients in
      the supine, upright flexion, and upright extension positions. The midsagittal
      diameter of the dural sac was measured at the level of the disks on MR images and
      myelograms. Foraminal sizes on the MR images were scored independently by two
      observers. RESULTS: Correlation between MR imaging and myelographic measurements
      was high (r = .81-.97). A small but statistically significant positional
      dependence of the dural sac diameter was found in the lower lumbar spine.
      Position-dependent differences in foraminal scores were uncommon. CONCLUSION:
      Quantitative assessment of sagittal dural sac diameters is comparable between
      lumbar myelography and positional MR imaging. In a selected patient population,
      only small changes in the sagittal diameter of the dural sac and foraminal size
      can be expected between various body positions, and the information gained in
      addition to that from  standard MR imaging is limited [corrected].

PMID- 9577487
TI  - Cognitive stimulation with the Wisconsin Card Sorting Test: functional MR imaging
      at 1.5 T.
AB  - PURPOSE: To determine whether functional magnetic resonance (MR) imaging can
      demonstrate a specific pattern of cerebral activation during cognitive
      stimulation by using a high-level cognitive task such as the Wisconsin Card
      Sorting Test. MATERIALS AND METHODS: Thirty-one healthy volunteers underwent
      functional MR imaging with a 1.5-T MR imager with a standard head coil (100/50
      [repetition time msec/echo time msec], 230-mm field of view, 40 degrees flip
      angle, 256 x 256 matrix). For stimulation, a personal computer version of the
      Wisconsin Card Sorting Test was used. Image analysis was done off-line, and cross
      correlation coefficients between the stimulus function and the signal intensity
      response were calculated on a pixel-by-pixel basis and overlaid onto the
      corresponding anatomic MR image for each volunteer. RESULTS: Stimulation resulted
      in strongly frontal activation, which included the mesial and the dorsolateral
      prefrontal cortexes, interconnected with Brodmann areas 44, 45, and 46. While
      activation was often bilateral, the largest area of activation was in the right
      hemisphere. Activation also was found in the basal ganglia and the mesial
      thalamic nuclei. CONCLUSION: Functional MR imaging can demonstrate a specific
      pattern during activation with a cognitive task. Functional MR imaging has
      promise for more precise anatomic and functional imaging studies of brain
      interaction than have other imaging modalities.

PMID- 9577488
TI  - Thyroid gland after total laryngectomy: CT appearance.
AB  - PURPOSE: To determine the computed tomographic (CT) appearance of the normal
      thyroid gland after total laryngectomy, because the high attenuation (or
      heterogeneous attenuation) of thyroid parenchyma was misinterpreted as tumor on
      several CT studies. MATERIALS AND METHODS: A search of computerized clinical
      files compiled from January 1996 through August 1997 yielded data on 24 patients
      who had undergone laryngectomy and subsequent CT of the neck. From these 24
      patients, CT findings were available in 21. Because one patient had undergone
      total thyroidectomy and was excluded from the study, a retrospective review was
      performed in the remaining 20 patients. RESULTS: In 14 patients, unilateral
      thyroid tissue was present; in the other six there was bilateral thyroid tissue
      not connected by an isthmus. Thus, there were 26 remaining thyroid lobes, of
      which six were round and 20 were oval or lobular. Nineteen lobes showed
      homogeneously high attenuation (including one scanned without use of contrast
      material), six showed heterogeneous high attenuation or contained areas of
      hyperlucency, and one was obscured by streak artifact. CONCLUSION: Thyroid tissue
      can appear as unilateral or bilateral asymmetric masses on neck CT scans after
      laryngectomy. Gland tissue can show homogeneously or heterogeneously high
      attenuation. Familiarity with the varied postoperative appearance of normal
      thyroid gland can prevent its misdiagnosis as tumor.

PMID- 9577489
TI  - Septic metastatic endophthalmitis from Klebsiella pneumoniae liver abscess: CT
      and MR imaging characteristics--report of three cases.
AB  - Computed tomography (CT) and magnetic resonance (MR) imaging were performed in
      three diabetic patients with endophthalmitis and liver abscess secondary to
      Klebsiella pneumoniae infection. Ocular abnormalities included early uveoscleral
      thickening, fulminant exudative vitreous humor, and late phthisis bulbi.
      Characteristic imaging findings of endophthalmitis in diabetic patients with
      liver abscess should raise a high index of suspicion for K pneumoniae infection.

PMID- 9577490
TI  - Allergic fungal sinusitis: CT findings.
AB  - PURPOSE: To determine the computed tomographic (CT) findings in patients with
      allergic fungal sinusitis. MATERIALS AND METHODS: The authors retrospectively
      reviewed CT scans and surgical and histopathologic reports in 45 patients (27
      male, 18 female; age range, 8-68 years) with allergic fungal sinusitis from
      multiple institutions. The median age (25 years) and demographics of the patients
      were determined. Two head and neck radiologists together evaluated the CT scans
      for the presence of intrasinus high-attenuation areas, extent of sinus
      involvement, bone expansion and thinning, bone erosion, and extension of disease
      into the adjacent soft tissues. RESULTS: Allergic fungal sinusitis was more
      common in male patients and in patients aged 20-30 years. All patients had
      increased intrasinus attenuation at non-contrast material-enhanced CT. Multiple
      sinus involvement occurred in 43 patients. Bilateral involvement was more common
      than unilateral disease. Forty-four patients had complete opacification of at
      least one of the involved sinuses; 43 of these patients had expansion of an
      involved sinus, 42 had remodeling and thinning of the bony sinus walls, and 41
      had erosion of the sinus wall. CONCLUSION: Allergic fungal sinusitis is a
      distinct clinical entity with nonspecific symptoms that may be initially
      suggested by the CT findings. These findings should alert the clinician to the
      possibility of allergic fungal sinusitis and prompt other diagnostic studies to
      establish the diagnosis and treatment plan.

PMID- 9577491
TI  - Dural carotid cavernous fistulas: role of conventional radiation therapy--long
      term results with irradiation, embolization, or both.
AB  - PURPOSE: To evaluate the long-term results of irradiation alone or of
      embolization with or without irradiation in patients with dural carotid cavernous
      fistulas (DCCFs). MATERIALS AND METHODS: Between 1984 and 1996, symptomatic DCCFs
      in 26 patients were treated by using irradiation alone (protocol 1, n = 12)
      before April 1988 and by using embolization as an initial treatment (protocol 2,
      n = 14) during and after April 1988. When angiography showed no improvement after
      embolization, irradiation was added (n = 6). On the basis of drainage flow speed,
      DCCFs were classified as fast, medium, or slow. RESULTS: With irradiation alone,
      all six patients with slow- to medium-type DCCFs had cure with a mean follow-up
      of 62 months. Four of six patients with fast-type DCCFs had cure or improvement,
      but the remaining two had no change. In the embolization group, irradiation was
      added in six patients with fast-type DCCFs. With a mean follow-up of 24 months,
      four of the six patients had cures, one had improvement, and one had no clinical
      change. Those who underwent protocol 2 had cures significantly earlier than those
      who underwent protocol 1 (P < .05). CONCLUSION: Conventional radiation therapy
      resulted in cure of DCCFs in nine (75%) of the 12 patients and in improvement of
      signs and symptoms in one (8%). Fast-type DCCFs may not always be improved.
      Radiation therapy may be useful in DCCFs after embolization.

PMID- 9577492
TI  - Oncologic diagnosis with 2-[fluorine-18]fluoro-2-deoxy-D-glucose imaging: dual
      head coincidence gamma camera versus positron emission tomographic scanner.
AB  - PURPOSE: To compare the performance of a dual-head single photon emission
      computed tomographic (SPECT) Anger camera operated in coincidence mode with that
      of a dedicated positron emission tomographic (PET) scanner in the imaging of
      cancer with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). MATERIALS AND METHODS:
      Thirty-one patients with known or suspected malignant neoplasms underwent imaging
      with both methods, and the images were read blindly. Diagnostic performance on a
      lesion-by-lesion basis was compared with attenuation-corrected PET as the
      standard of reference. RESULTS: Of a total of 109 discrete lesions depicted at
      PET, 60 (relative sensitivity, 55%) were identified on the coincidence-mode
      images. Of the nodules or masses depicted at PET, 13 (93%) of 14 lung nodules or
      masses, 20 (65%) of 31 mediastinal lymph nodes, five (71%) of seven lesions in
      the neck, five (55%) of nine axillary lymph nodes, 11 (50%) of 22 bone
      metastases, and six (23%) of 26 abdominal tumor deposits were correctly
      identified on the coincidence gamma camera images. CONCLUSION: These preliminary
      findings indicate FDG imaging with a modified dual-detector gamma camera
      operating in coincidence mode can depict many of the lesions depicted with a PET
      scanner, particularly in the lungs. Sensitivity for lesions detected at dedicated
      FDG PET was poor in the abdomen and in all locations outside the lungs for tumor
      deposits generally less than 1.5 cm in short-axis diameter.

PMID- 9577493
TI  - The ring sign.

PMID- 9577494
TI  - Characteristics of radiology groups and of diagnostic radiologists and radiation
      oncologists in different types of practices.
AB  - PURPOSE: To describe the characteristics of U.S. radiology groups and of
      radiologists in different types of practices in 1995. MATERIALS AND METHODS: A
      survey was distributed to 3,024 radiologists; the response rate was 75%.
      Responses were weighted to represent all U.S. groups or radiologists. RESULTS:
      There were 3,285 groups; 340 were academic, and 356 were multispecialty. Fifty
      percent of groups had two to four members; 39% of radiologists were in groups
      with fewer than eight members, and 8% were solo practitioners. Seventy percent of
      all radiologists were in practices owned entirely by physicians in the practice,
      and 80% of these were themselves owners. Eight percent of radiologists were in
      government-owned practices, and 15% (primarily academic) were in privately-owned
      practices in which all physicians were employees. Sixty-nine percent of academic
      diagnostic radiologists worked primarily in one field, but this was true of only
      22% of those in nonacademic groups. Solo diagnostic practitioners also typically
      had a broad practice but excluded high-cost modalities. Radiologists in
      nonacademic groups averaged more vacation days (30 d/yr) than academic (19 d/yr)
      or solo (12 d/yr) practitioners. Solo and locum tenens practitioners were
      relatively old; academic radiologists, relatively young. CONCLUSION: Through
      1995, average group size has grown slowly. There are important differences among
      practice types, especially between academic and nonacademic practices.

PMID- 9577495
TI  - Breast lesion localization: a freehand, interactive MR imaging-guided technique.
AB  - PURPOSE: To evaluate interactive magnetic resonance (MR) imaging-guided
      preoperative needle localization and hookwire placement in the noncompressed
      breast in patients in the prone position. MATERIALS AND METHODS: Nineteen MR
      imaging-guided breast lesion localization procedures were performed in 17
      patients aged 38-70 years (mean age, 48 years) by using an open-platform breast
      coil in either a 1.5-T, closed-bore imager (n = 14) or a 0.5-T, open-bore imager
      (n = 5). Rapid imaging (fast spin-echo, water-selective fast spin-echo, or water
      specific three-point Dixon gradient-echo) was alternated with freehand
      manipulation of an MR-compatible needle to achieve accurate needle placement.
      RESULTS: Up to three manipulations of the needle were required during an average
      of 9 minutes to reach the target lesion. MR imaging findings confirmed the final
      needle position within 9 mm of the target in all cases. The accuracy of 10
      localizations was independently corroborated either at mammography or at
      ultrasonography. Nine lesions were visible on MR images only. CONCLUSION:
      Interactive MR imaging-guided, freehand needle localization is simple, accurate,
      and requires no special stereotactic equipment. Lesions throughout the breast,
      including those in the anterior part of the breast and those near the chest wall,
      which can be inaccessible with standard grid or compression-plate techniques, can
      be localized. A variety of needle trajectories in addition to the horizontal path
      are possible, including circumareolar approaches and tangential needle paths
      designed to avoid puncture of implants.

PMID- 9577496
TI  - Automated detection of breast carcinomas not detected in a screening program.
AB  - PURPOSE: To investigate the possibility of automated detection of early signs of
      cancer that were not detected in a breast cancer screening program. MATERIALS AND
      METHODS: A set of 75 mammograms (in 65 women) with subtle circumscribed masses,
      stellate lesions, and architectural distortions that were not detected in a
      screening program by two radiologists was assembled and extended with 142 normal
      mammograms (contralateral mammograms in the same 65 women). An automated system
      for the detection of circumscribed masses and stellate lesions was applied to
      this set. RESULTS: In 22 (34%) of 65 cases, an early sign of cancer was detected
      at a specificity of one false-positive finding per image. At a specificity of
      three false-positive findings per image, 39 (60%) of the cancers were detected.
      Of the tumors that were classified as screening errors, seven (50%) were found at
      a specificity of 0.5 false-positive finding per image. CONCLUSION: A substantial
      proportion of cancers that were missed in a screening program, despite double
      reading, were found with this detection method at less than one false-positive
      finding per image.

PMID- 9577497
TI  - Mammographic technologist job satisfaction: what radiologists need to know-
      results of a large national survey.
AB  - PURPOSE: To determine mammographic technologists' overall level of job
      satisfaction, the variables that correlate with job satisfaction, and whether job
      satisfaction has changed since 1987. MATERIALS AND METHODS: A 29-item, scannable
      survey was mailed randomly to 5,000 mammographic technologists. Survey items were
      related to work setting, job description, rate of pay and other benefits,
      experience, education, age, and overall job satisfaction. The results were
      compared with those of a 1987 survey of general radiologic technologists.
      RESULTS: A total of 1,503 technologists responded to the survey. On a five-point
      scale, in which 5 represents very satisfied, the mean rating of job satisfaction
      +/- the standard deviation was 3.4 +/- 0.9; 83.1% of technologists rated overall
      satisfaction as 3 or higher compared with 86% of general technologists who
      reported being satisfied with their jobs in 1987. Regression analysis revealed
      that enjoyment from working with fellow mammographic technologists and enjoyment
      from working with radiologists (combined adjusted R2, 26.5%) correlated
      significantly with increased job satisfaction. CONCLUSION: Mammographic
      technologist job satisfaction is high and similar to that of general radiologic
      technologists, as reported in 1987. Survey results indicate that the most
      important variable related to mammographic technologist job satisfaction is the
      technologist-radiologist relationship; a negative relationship results in lower
      job satisfaction, which can affect job performance and patient care.

PMID- 9577498
TI  - Effect of film-based versus filmless operation on the productivity of CT
      technologists.
AB  - PURPOSE: To determine the relative time required for a technologist to perform a
      computed tomographic (CT) examination in a "filmless" versus a film-based
      environment. MATERIALS AND METHODS: Time-motion studies were performed in 204
      consecutive CT examinations. Images from 96 examinations were electronically
      transferred to a picture archiving and communication system (PACS) without being
      printed to film, and 108 were printed to film. The time required to obtain and
      electronically transfer the images or print the images to film and make the
      current and previous studies available to the radiologists for interpretation was
      recorded. RESULTS: The time required for a technologist to complete a CT
      examination was reduced by 45% with direct image transfer to the PACS compared
      with the time required in the film-based mode. This reduction was due to the
      elimination of a number of steps in the filming process, such as the printing at
      multiple window or level settings. CONCLUSION: The use of a PACS can result in
      the elimination of multiple time-intensive tasks for the CT technologist,
      resulting in a marked reduction in examination time. This reduction can result in
      increased productivity, and, hence greater cost-effectiveness with filmless
      operation.

PMID- 9577499
TI  - Incidental lung carcinoma detected at CT in patients selected for lung volume
      reduction surgery to treat severe pulmonary emphysema.
AB  - PURPOSE: The authors present their experience with previously unsuspected
      carcinoma of the lung detected at preoperative computed tomography (CT) in
      patients with severe pulmonary emphysema who were scheduled to undergo lung
      volume reduction surgery. MATERIALS AND METHODS: Preoperative chest CT was
      performed in 148 patients (84 men, 64 women; mean age, 65 years +/- 8 [standard
      deviation]) with advanced pulmonary emphysema before lung volume reduction
      surgery. At surgery, an attempt was made to excise any pulmonary nodule
      considered suspicious for carcinoma at CT. RESULTS: Eighteen pulmonary nodules
      suspicious for lung cancer were found at CT in 17 (11%) of the 148 patients.
      Sixteen of these 148 nodules were resected at lung volume reduction surgery. Nine
      non-small cell carcinomas (adenocarcinoma, n = 4, including three with
      bronchioloalveolar differentiation; poorly differentiated, n = 3; squamous cell
      carcinoma, n = 2) were found in eight (5%) patients. Eight of the cancers were
      stage I, and one was unstaged surgically. Maximum diameters of the cancers ranged
      between 1.0 and 3.8 cm (median, 1.6 cm). The seven (5%) other resected nodules
      were all benign. CONCLUSION: A 5% rate of stage I primary lung cancer in patients
      selected for lung volume reduction surgery suggests that performance of chest CT
      in candidates for lung volume reduction surgery is appropriate not only to
      identify patterns of pulmonary parenchymal destruction but also to search for
      stage I lung cancer.

PMID- 9577500
TI  - Tunneled hemodialysis catheters: use of a silver-coated catheter for prevention
      of infection--a randomized study.
AB  - PURPOSE: To determine whether silver-coated tunneled hemodialysis catheters
      reduce infection and to determine the frequency of central venous thrombosis and
      stenosis with percutaneous placement of right internal jugular vein dialysis
      catheters by interventional radiologists. MATERIALS AND METHODS: Ninety-one
      patients were randomly assigned to a treatment (silver-coated catheter; n = 47)
      or control (identical catheter without silver coating; n = 44) arm. Baseline
      venography was performed. Catheter tips were cultured and venography was repeated
      at catheter removal. RESULTS: Mean duration of catheter placement was 92 days.
      Infection occurred in 11 patients (five in the treatment group, six in the
      control group). Tip cultures in 15 patients (eight treatment, seven control) were
      positive without clinical infection. Infection and colonization rates were
      slightly but not significantly higher in the treatment group than in the control
      group. Silver-coated catheters in two (4%) patients were removed due to reaction
      to the coating. Completion venograms (n = 72) showed new minor abnormalities in
      four (6%) patients and major abnormalities (stenosis, thrombosis) in three (4%)
      patients. Permanent venous abnormalities occurred in two (3%) patients.
      CONCLUSION: Silver coating does not confer a benefit against clinical infection
      or colonization. Interventional radiologic placement of tunneled dialysis
      catheters yields a low frequency of permanent central venous thrombosis and
      stenosis.

PMID- 9577501
TI  - Renal artery stenosis and accessory renal arteries: accuracy of detection and
      visualization with gadolinium-enhanced breath-hold MR angiography.
AB  - PURPOSE: To determine the accuracy of gadolinium-enhanced breath-hold magnetic
      resonance (MR) angiography in the diagnosis of renal artery stenosis and
      visualization of accessory renal arteries. MATERIALS AND METHODS: Forty-four
      patients suspected of having renal artery stenosis and 10 potential kidney
      donors, all of whom were scheduled to undergo elective intraarterial digital
      subtraction angiography (DSA), were studied. Three-dimensional gradient-echo
      gadolinium-enhanced MR angiography was performed at 1.5 T with the following
      parameters: repetition time, 13.5 msec; echo time, 3.5 msec; flip angle, 60
      degrees; 195 x 512 matrix; 400-mm field of view; and 6-cm imaging volume
      consisting of 15 4-mm-thick partitions reconstructed every 2 mm. Gadopentetate
      dimeglumine (30 mL) was injected with a power injector. MR angiograms were
      assessed before the standard of reference, intraarterial DSA, was performed.
      RESULTS: Four MR angiograms were not evaluable because of poor image quality. MR
      angiography enabled visualization of all but one of the 121 arteries. In four
      small accessory arteries, a stenosis could not be excluded owing to inadequate
      spatial resolution. MR angiography enabled the correct diagnosis in 30 of the 31
      arteries with a grade 2 (50%-99%) stenosis and in seven of the 10 occluded
      arteries. Sensitivity and specificity for correct identification of a grade 2
      stenosis were 97% and 92%, respectively. CONCLUSION: Gadolinium-enhanced MR
      angiography is an accurate, minimally invasive method for detecting renal artery
      stenosis and is reliable for visualizing accessory renal arteries.

PMID- 9577502
TI  - Distal lower extremity arteries: evaluation with two-dimensional MR digital
      subtraction angiography.
AB  - PURPOSE: To test the hypothesis that magnetic resonance (MR) digital subtraction
      angiography is superior to two-dimensional time-of-flight (TOF) MR angiography
      for demonstration of patent arteries in the distal lower extremity. MATERIALS AND
      METHODS: Thirty-seven lower extremities in 23 consecutive patients were imaged
      with two-dimensional TOF MR angiography and two-dimensional MR digital
      subtraction angiography. Images were interpreted in a randomized and blinded
      manner. Each lower extremity was subdivided into seven potential arterial
      segments. The number of digital arteries visualized was also determined. Overall
      image quality of MR digital subtraction and TOF angiograms was compared. The
      relative ability of MR digital subtraction angiography and TOF MR angiography to
      demonstrate patent arterial segments was assessed. RESULTS: MR digital
      subtraction angiography was significantly superior to TOF MR angiography for
      demonstration of patent arterial segments and digital arteries (P < .001). MR
      digital subtraction angiographic images were qualitatively superior to TOF images
      (P < .001). CONCLUSION: Two-dimensional MR digital subtraction angiography is
      superior to two-dimensional TOF MR angiography for help in identifying patent
      segments in the distal lower extremity.

PMID- 9577503
TI  - Malignant dysphagia: palliation with esophageal stents--long-term results in 100
      patients.
AB  - PURPOSE: To evaluate the long-term palliative effect of self-expanding nitinol
      esophageal stents in patients with malignant dysphagia. MATERIALS AND METHODS:
      One hundred patients with severe dysphagia secondary to malignant esophageal
      strictures were treated with self-expanding nitinol stents. The strictures were
      caused by squamous carcinoma (n = 43), adenocarcinoma (n = 28), anastomotic tumor
      recurrence (n = 14), and mediastinal tumor (n = 15). RESULTS: One hundred six
      stents were successfully positioned in 100 patients. Attempts to insert a second,
      coaxial stent were unsuccessful in two patients; a second stent was placed
      incorrectly in another patient. Statistically significant (P < .001) reduction of
      dysphagia was noted after expansion of the stents. Complications consisted of
      incomplete expansion secondary to stent twisting (n = 4), stent migration (n =
      4), tumor ingrowth (n = 17), tumor overgrowth (n = 3), food impaction (n = 5),
      fracture of stent wires (n = 2), benign strictures at stent edges (n = 2), tumor
      bleeding (n = 3), and esophagorespiratory fistula (n = 5). The primary patency
      rate was 75% (77 of 102 stents); the secondary patency rate was 94% (96 of 102
      stents). The survival time (mean, 6.2 months; range, 0.1-47 months) varied with
      the diagnosis. CONCLUSION: Placement of self-expanding nitinol stents is safe and
      has a good long-term palliative effect on dysphagia in patients with malignant
      esophageal strictures.

PMID- 9577504
TI  - Platinum coil-mediated implantation of growth factor-secreting endovascular
      tissue grafts: an in vivo study.
AB  - PURPOSE: To demonstrate in vivo that platinum embolic coils can be used to
      deliver genetically modified, growth factor-secreting fibroblast grafts into the
      endovascular space with the long-term goal of improving fibrosis within coil
      embolized cerebral aneurysms. MATERIALS AND METHODS: Murine fibroblasts that
      contained multiple inserts of the DNA for human basic fibroblast growth factor
      were grown in culture onto 10-mm-long segments of Guglielmi detachable coils.
      Control (n = 4) and fibroblast-bearing (n = 4) coils were implanted into the
      common carotid artery in nude rats. The arterial segments that contained the coil
      were harvested after 14 or 35 days. Cellular content and collagen formation in
      the treated vessels were assessed histologically. RESULTS: At both 14 and 35
      days, samples with control coils showed primarily involuting blood elements with
      minimal fibroblast proliferation or collagen formation. At 14 days, samples with
      fibroblast-bearing coils showed extensive fibroblast proliferation. At 35 days,
      samples with fibroblast-bearing coils showed marked interval fibroblast
      proliferation and collagen formation. CONCLUSION: Platinum coils can be used as a
      cell delivery device. Direct intravascular implantation of growth factor
      secreting fibroblast grafts leads to improved intravascular scar formation,
      therefore theoretically reducing the potential for aneurysm regrowth or coil
      compaction.

PMID- 9577505
TI  - Neonatal pig brain: lack of heating during Doppler US.
AB  - PURPOSE: To evaluate potential local brain-heating effects of Doppler ultrasound
      (US) at high power output settings. MATERIALS AND METHODS: After craniotomy, a
      temperature probe was inserted into deep white matter or basal ganglia in 12
      anesthetized newborn piglets. The range gate and focal zone were placed directly
      over the temperature sensor. Brain and core (rectal) temperatures were measured
      before and during 5 minutes of continuous transdural duplex or color Doppler US,
      with transmitter power output settings of less than 500 mW in situ spatial peak
      temporal average or less than 800 mW in situ spatial peak temporal average.
      Temperature also was measured during administration of a US contrast agent with
      duplex US at less than 500 mW in situ spatial peak temporal average and after
      death at the same output setting. RESULTS: Maximal differences between the
      baseline and the post-US temperatures were, on average, less than 0.3 degree C (P
      > .5) and were highly correlated with changes in core temperature (r = .9, P <
      .001). Addition of the contrast agent did not result in focal brain heating
      during pulsed Doppler US (P > .6). There was no association between an increase
      in estimated power output and brain temperature change (P = .9). In addition,
      brain ischemia (postmortem exposure) was not associated with focal brain heating
      during pulsed Doppler US. CONCLUSION: Transfontanellar Doppler US alone or with
      administration of a contrast agent does not produce statistically significant
      focal brain heating at high transmitter power levels.

PMID- 9577506
TI  - MS-325: albumin-targeted contrast agent for MR angiography.
AB  - PURPOSE: To evaluate the protein-binding and signal enhancement characteristics
      of MS-325, a gadolinium-based magnetic resonance (MR) imaging blood pool agent
      that binds to albumin, and compare results with those obtained with existing
      gadolinium- and iron oxide-based agents. MATERIALS AND METHODS: Protein binding
      in human plasma was measured by means of ultrafiltration. T1 relaxation times (20
      MHz) were measured in human plasma or ex vivo samples from rabbits and monkeys
      injected with 0.1 mmol of MS-325 per kilogram of body weight. Imaging (three
      dimensional fast imaging with steady-state precession, or FISP) was performed at
      1.0 T in phantoms, which contained varying concentrations of different agents, or
      rabbits after injection of 0.015-0.100 mmol/kg MS-325. RESULTS: MS-325 is 80%-96%
      bound in human plasma and exhibits a relaxivity approximately six to 10 times
      that of gadolinium diethylenetriaminepentaacetic acid (DTPA). Images of phantoms
      containing MS-325 were significantly brighter than those containing existing
      gadolinium chelates or iron particles (monocrystalline iron oxide nanoparticle,
      or MION) at equivalent concentrations. Findings of in vivo studies indicated
      strong, persistent plasma T1 reduction with MS-325 for 1 hour (T1 of MS-325, 50
      100 msec; T1 of Gd-DTPA, 200-400 msec) and strong vascular enhancement on MR
      images. CONCLUSION: MS-325 is highly protein bound after injection and provides
      vascular signal enhancement superior to that provided with other agents. As the
      first gadolinium-based blood pool agent in human trials, MS-325 has the potential
      to enhance both dynamic and steady-state MR angiograms.

PMID- 9577507
TI  - Steady-state and dynamic MR angiography with MS-325: initial experience in
      humans.
AB  - PURPOSE: To evaluate the imaging performance and patient tolerance of a blood
      pool contrast agent (MS-325) for magnetic resonance (MR) angiography. MATERIALS
      AND METHODS: Imaging of peripheral and carotid vessels was performed in seven
      healthy volunteers in a phase I clinical trial of the gadolinium chelate MS-325.
      Each volunteer received an intravenous injection of 0.05 mmol/kg MS-325 over 30
      seconds. Dynamic (arterial phase) and steady-state (arterial-venous phase) three
      dimensional gradient-echo MR angiograms were acquired during, immediately after,
      and approximately 50 minutes after injection. Images were ranked (1 [poor] to 5
      [excellent]) for overall image quality, and signal-to-noise ratio (S/N) and
      contrast-to-noise ratio (C/N) were measured by using standard techniques.
      RESULTS: All volunteers tolerated the procedure well. The MS-325-enhanced studies
      demonstrated intense vascular signal. Mean peripheral arterial C/N was 12.9 +/-
      4.8 (standard deviation), 78.8 +/- 29.4, 46.1 +/- 10.9, and 41.9 +/- 14.1 for the
      two-dimensional (2D) time-of-flight (TOF) and the contrast material-enhanced
      dynamic, early steady-state, and late steady-state images, respectively. Image
      quality of steady-state postcontrast images was statistically significantly (P <
      .02) higher than that of 2D TOF images. Image quality of early and late
      postcontrast images was similar, but a small (10%) decrease in C/N was noted from
      early to late images. CONCLUSION: MS-325 provides excellent vascular and
      selective arterial enhancement during dynamic MR angiography. The long blood
      residence time also allows acquisition of steady-state images of the arteries and
      veins with excellent spatial resolution.

PMID- 9577508
TI  - Disparity mapping applied to sonography of the breast: technical note.
AB  - A two-dimensional sonoelastographic technique called "disparity mapping" was
      applied to breast sonographic examinations in eight patients to test
      discrimination between benign and malignant lesions. With probe compression,
      pairs of gray-scale sonographic scans were obtained about 1 second apart. The
      disparity mapping procedure calculated the apparent displacement of the speckle
      pattern about each point in the image and presented that information in the form
      of a disparity map. Findings were consistent with a firm lesion in two of the
      three cancers, were indistinguishable from normal tissue in all three
      fibroadenomas, were indistinguishable from normal findings in one cyst, and
      showed no disparity in one cyst because it had few internal echoes.

PMID- 9577509
TI  - Chronic thromboembolism.

PMID- 9577510
TI  - Fatal cardiac perforation.

PMID- 9577512
TI  - Diagnostic imaging for low back pain.

PMID- 9577511
TI  - Hepatocellular carcinoma with portal vein tumor thrombus.

PMID- 9577513
TI  - Long acting beta 2 agonists and the risk of life threatening asthma.

PMID- 9577514
TI  - The failing health care system for adult patients with cystic fibrosis.

PMID- 9577515
TI  - Case-control study of salmeterol and near-fatal attacks of asthma.
AB  - BACKGROUND: A case-control study was undertaken to investigate the hypothesis
      that the use of the long acting beta agonist salmeterol increases the risk of a
      near-fatal attack of asthma. METHODS: The cases comprised admissions to the
      intensive care unit (ICU) for asthma in 14 major hospitals within the Wessex
      region in 1992. For each of the cases four age-matched controls were selected
      from asthma admissions to the same hospital during the same period. Information
      on prescribed drug therapy for the 48 cases and 185 controls was collected from
      the hospital admission records. RESULTS: The patients admitted to the ICU had
      greater chronic asthma severity and had generally been prescribed more asthma
      drugs than the control admissions to hospital. The relative risk of a near-fatal
      attack of asthma in patients prescribed inhaled salmeterol was 2.32 (95% CI 1.05
      to 5.16), p = 0.04. However, the salmeterol relative risk decreased to 1.42 (95%
      CI 0.49 to 4.10), p = 0.52 when the analysis was restricted to the more
      chronically severe patients (those in the subgroup of patients with a hospital
      admission for asthma in the previous 12 months). These findings suggest that the
      increased unadjusted relative risk with salmeterol is predominantly due to
      confounding by severity--that is, the increased relative risk is due to patients
      with more severe asthma (at greatest risk of a near-fatal asthma attack) being
      preferentially prescribed salmeterol. This interpretation is supported by the
      finding in this study that, within the control group (selected from the
      population of asthmatics requiring hospital admission), salmeterol was
      preferentially prescribed to the most severe patients (a threefold greater
      prescription of salmeterol to control patients if they had been admitted to
      hospital in the 12 months prior to the index admission). There was no increased
      risk of a near-fatal attack of asthma in patients prescribed a beta agonist by
      metered dose inhaler (OR 0.75 (95% CI 0.31 to 1.78), p = 0.51). In contrast, the
      relative risks for beta agonists delivered by nebulisation (OR 3.86 (95% CI 1.99
      to 7.50), p < 0.001) and oral theophylline (OR 2.45 (95% CI 1.26 to 4.78), p <
      0.01) were increased and did not markedly decrease when the analysis was
      restricted to the more severe asthmatic subjects. CONCLUSIONS: Although these
      findings are not conclusive, particularly because of the small numbers involved
      in some subgroup analyses, they suggest that the use of salmeterol by patients
      with chronic severe asthma is not associated with a significantly increased risk
      of a near-fatal attack of asthma. If a near-fatal asthma attack is considered to
      be an intermediate step in a process by which a severe attack of asthma may
      become fatal, these results would suggest that salmeterol is unlikely to be
      associated with an increased risk of death, at least by this mechanism.

PMID- 9577516
TI  - Determinants of management errors in acute severe asthma.
AB  - BACKGROUND: It is hypothesised that, despite recent initiatives to improve asthma
      self-management including asthma education, detailed investigation of the
      sequence of events culminating in hospital admission will lead to the
      identification of important management errors and thus the likelihood that the
      majority of severe asthma attacks are preventable by currently available
      strategies, and that psychological, health care and socioeconomic factors are
      risk factors for such management errors. METHODS: A cross sectional study was
      undertaken of 138 patients aged 15-50 years admitted to hospital (general ward or
      intensive care unit) with acute severe asthma who were assessed within 24-72
      hours of admission using a number of previously validated instruments. A detailed
      history of events of the attack was assessed against predetermined criteria for
      non or delayed use of oral corticosteroids and non or delayed use of emergency
      ambulance services. RESULTS: Subjects had evidence of severe chronic asthma and
      had acute severe asthma at presentation (n = 90, pH = 7.3 (0.2), PaCO2 = 7.2
      (5.0) kPa) but duration of hospital stay was short (3.7 (2.6) days). Serious
      management errors occurred very frequently and most were deemed to have been made
      by the patient. Forward stepwise regression revealed that delayed or non-use of
      oral corticosteroids was predicted independently by lack of paying job (p =
      0.02), high total use of inhaled beta agonists in the 24 hours before index
      admission (p = 0.04), loss of a job in the last year (p = 0.04), low frequency of
      use of oral corticosteroids in the last year (p = 0.06), concerns during the
      index attack about medical expenses (p = 0.07), and delay in the use of ambulance
      services (p = 0.05)--the model being responsible for 23% of the variance. Delayed
      or non-summoning of emergency ambulance services was predicted independently by
      total life events (p = 0.03), having something stolen in the last year (p =
      0.003), panic during the index attack (p = 0.01), and concerns during the index
      attack about taking time off work (p = 0.07)--the model being responsible for 21%
      of the variance. CONCLUSIONS: The results of this study show that, despite recent
      educational advances, serious management errors are common in those admitted to
      hospital with acute severe asthma and that most management errors relate to
      patient self-management behaviour. Serious management errors are predicted by a
      variety of socio-economic and psychological factors. While the results of this
      study are consistent with the widely held view that most acute severe attacks are
      theoretically preventable, the challenge for the future is to change patients'
      behaviour in the face of considerable adverse socioeconomic and psychological
      factors.

PMID- 9577517
TI  - Expression of growth factors and remodelling of the airway wall in bronchial
      asthma.
AB  - BACKGROUND: Bronchial asthma is characterised by airway structural changes,
      including mucosal inflammatory infiltration and subepithelial collagen
      deposition, that may represent the morphological basis for the chronicity of the
      disease. The relationship between airway wall thickness and growth factors in
      asthma has not been elucidated. METHODS: Bronchial biopsy specimens were obtained
      from 21 asthmatic patients and eight healthy subjects and the basement membrane
      thickness was measured by light microscopy and electron microscopy. At the same
      time the numbers of eosinophils and fibroblasts were assessed and the expression
      of transforming growth factor beta 1 (TGF-beta 1), platelet derived growth factor
      (PDGF), and insulin like growth factor (IGF) I in the bronchial mucosa was
      examined by immunostaining. The relationship between the degree of thickening of
      the subepithelial layer and both the clinical data and pulmonary function were
      also investigated. RESULTS: The basement membrane of the asthmatic patients was
      thicker than that of the healthy controls (median 8.09 versus 4.02 microns).
      Electron microscopic examination of the basement membrane revealed thickening of
      the subepithelial lamina reticularis; this thickening significantly correlated
      with the number of fibroblasts in the submucosa in the asthmatic subjects (rs =
      0.88) but not in the controls (rs = 0.70). There was a significantly higher
      number of eosinophils in the airways of the asthmatic subjects than in the
      healthy subjects (EG1 + cells: 52.0 versus 2.0/mm2, EG2 + cells: 56.0 versus
      1.5/mm2). The expression of each growth factor in the bronchial mucosa was
      similar in asthmatic and healthy subjects (TGF-beta 1: 18.0% versus 16.0%, PDGF:
      37.0% versus 32.5%, IGF-I: 15.0% versus 8.0%). A weak but statistically
      significant correlation was found between the number of fibroblasts and the
      expression of TGF-beta 1 in asthmatic subjects (rs = 0.50). There was a
      significant correlation between the thickness of the subepithelial layer in
      asthmatic subjects and the attack score (rs = 0.58) and a significant inverse
      correlation between the subepithelial collagen thickness in asthmatic subjects
      and airway hypersensitivity (rs = -0.65). CONCLUSIONS: These findings indicate
      that the thickening of the subepithelial layer in bronchial asthma is due to an
      increase in fibroblasts, and that the thickness of the subepithelial collagen
      appears to be linked to an increase in bronchial responsiveness and exacerbation
      of clinical manifestations.

PMID- 9577518
TI  - Family size, childhood infections and atopic diseases. The Aberdeen WHEASE Group.
AB  - BACKGROUND: This study addresses the causes of the increases in childhood asthma
      and allergic disease. On the basis of an observed inverse relationship between
      family size and allergic disease or atopy, it has been proposed that a fall in
      common childhood infections may have been responsible for the rise in asthma.
      This study was undertaken to investigate the relationships between family size
      and reported allergic disease and to test the hypothesis that an inverse
      relationship between the two is a consequence of childhood infections. METHODS:
      Data had been obtained in a 1964 cross sectional survey of a random sample of
      Aberdeen schoolchildren aged between 10 and 14 in that year. Records of the
      presence or absence of asthma, eczema, or hay fever at the time of the survey and
      a history of measles, pertussis, varicella, rubella, and mumps before and after
      the age of three years were available for 2111 subjects. RESULTS: The risks of
      hay fever (odds ratio 0.2, 95% CI 0.1 to 0.8) and eczema (OR 0.3, CI 0.1 to 0.7)
      were inversely related to having had three or more older siblings, whilst the
      risk of asthma (OR 0.4, CI 0.1 to 0.9) was inversely related to having had three
      or more younger siblings. Increasing total numbers of siblings showed a
      significant trend in protection against both eczema and hay fever. A weak
      protective effect against asthma was found for measles after the age of three (OR
      0.5, CI 0.3 to 0.9) and slight increases in the risk of eczema were associated
      with having had rubella or pertussis and of asthma with having had varicella. The
      number of infections before the age of three was associated with a significant
      trend in the odds ratios towards increased risk of asthma (p = 0.025). There were
      significant trends in the odds ratios towards greater risk of eczema and hay
      fever with increasing exposure to rubella, mumps, and varicella. These relations
      between infection and atopic diseases were independent of the potential
      confounding factors age, sex, father's social class, and total number of
      siblings. CONCLUSIONS: These data add to the accumulating evidence that
      membership of a large sibship confers some protection against atopic disease.
      This does not appear to be explained by the common childhood infections which
      show conflicting relationships with atopic disease, in that measles may have some
      protective effect against asthma but the more infections a child has had, the
      more likely he or she is to have atopic disease. The explanation of the sibship
      effect is likely to lie elsewhere and the fall in common childhood infections is
      unlikely to explain the rise in atopic disease.

PMID- 9577520
TI  - Influence of excessive weight loss after gastroplasty for morbid obesity on
      respiratory muscle performance.
AB  - BACKGROUND: Morbidly obese subjects are known to have impaired respiratory
      function and inefficient respiratory muscles. A study was undertaken to
      investigate the influence of excessive weight loss on pulmonary and respiratory
      muscle function in morbidly obese individuals who underwent gastroplasty to
      induce weight loss. METHODS: Twenty one obese individuals with mean (SE) body
      mass index (BMI) 41.5 (4.5) kg/m2 without overt obstructive airways disease
      (FEV1/FVC ratio > 80%) were studied before and six months after vertical banded
      gastroplasty. Only patients who had lost at least 20% of baseline BMI were
      included in the study. Standard pulmonary function tests and respiratory muscle
      strength and endurance were measured. RESULTS: Before operation the predominant
      abnormalities in respiratory function were significant reductions in lung volumes
      and respiratory muscle endurance and, to a lesser degree, reductions in
      respiratory muscle strength. All parameters increased towards normal values after
      weight loss with significant increases in functional residual capacity (FRC) from
      84.0 (2.2) to 91.3 (2.5)% of predicted normal values (mean difference 7.3, 95%
      confidence interval of difference (CI) 4.2 to 10.5), total lung capacity (TLC)
      from 85.6 (3.0) to 93.5 (3.7)% of predicted normal values (mean difference 7.9,
      95% CI 4.5 to 11.5), residual volume (RV) from 86.7 (3.1) to 96.4 (3.0) of
      predicted normal values (mean difference 9.7, 95% CI 5.2 to 14.1), expiratory
      reserve volume (ERV) from 76.6 (3.0) to 89.0 (3.4)% of predicted normal values
      (mean difference 12.4, 95%, CI 6.3 to 18.9), respiratory muscle strength: PImax
      from 92 (4.4) to 113 (4.6) cm H2O (mean difference 21, 95% CI 12.2 to 31.6),
      PEmax from 144 (5.6) to 166 (4.3) cm H2O (mean difference 22, 95% CI 12.9 to
      32.0), and endurance: PmPeak/PImax from 56 (1.4) to 69 (2.0)% (mean difference
      13, 95% CI 9.7 to 16.9). The strongest correlation was between weight loss and
      the improvement in respiratory muscle endurance. CONCLUSIONS: Lung volumes and
      respiratory muscle performance are decreased in obese individuals. Weight loss
      following gastroplasty is associated with improvement in lung volumes and
      respiratory muscle function.

PMID- 9577519
TI  - Distribution, aerodynamic characteristics, and removal of the major cat allergen
      Fel d 1 in British homes.
AB  - BACKGROUND: Sensitisation to cat allergen (Fel d 1) is an important risk factor
      for asthma in the UK. A study was undertaken to investigate the distribution of
      cat allergen in British homes, the aerodynamic characteristics and particle size
      distribution of airborne Fel d 1, and the method of removing it. METHODS: Dust
      was collected from 50 homes with a cat and from 50 homes without a cat, and
      airborne levels of Fel d 1 were measured in 50 homes with a cat and 75 homes
      without a cat. Particle size distribution was determined using an Andersen
      sampler (8 hours/day) in 10 homes with cats. This was repeated on five separate
      days in a house with four cats, and then one, two, four, seven, and 14 days after
      the cats were removed from the living room area. The effect of high efficiency
      particulate air (HEPA) cleaner on airborne levels of Fel d 1 was investigated in
      seven homes with cats. Samples were collected on two separate days from two rooms
      of each house concurrently, one of which contained the cat, one day with the HEPA
      cleaner on and the other day as a control. Three one hourly samples were
      collected over a nine hour period (baseline, 4-5 hours, 8-9 hours) using a high
      volume dust sampler (air flow rate 60 l/min) and the air sample was collected
      onto a microglass fibre filter (pore size 0.3 micron). RESULTS: Fel d 1
      concentrations were much lower in houses without a cat than in those with a cat
      (260-fold difference (95% CI 167 to 590) in living room carpets: geometric mean
      (GM) 0.9 microgram/g (range 0.06-33.93) versus 237 micrograms/g (range 2.8-3000);
      314-fold difference (95% CI 167 to 590) in upholstered furniture: 1.21
      micrograms/g (range 0.06-61.9) versus 380 micrograms/g (range 7.1-6000); 228-fold
      difference (95% CI 109 to 478) in bedroom carpets: 0.24 microgram/g (range 0.06
      2.24) versus 55 micrograms/g (range 0.06-2304); and 215-fold difference (95% CI
      101 to 456) in mattresses: 0.2 microgram/g (range 0.06-2.3) versus 55
      micrograms/g (range 0.06-3400). Airborne levels of Fel d 1 were detected in all
      houses with cats, and the levels varied greatly between the homes (range 0.7-38
      ng/m3). Low concentrations of airborne Fel d 1 (range 0.24-1.78 ng/m3) were found
      in 22 of 75 homes without a cat. Although airborne Fel d 1 was mostly associated
      with large particles (> 9 microns, approximately 49% of the allergen recovered),
      small particles (< 4.7 microns) comprised approximately 23% of the total airborne
      allergen. Total airborne Fel d 1 was reduced by 61.7% two days after removal of
      the cat but this was due predominantly to the decrease in larger particles (> 4.8
      microns) which fell to 13% of their baseline level. Fel d 1 levels associated
      with small particles (< 4.8 microns) remained largely unchanged on days 1, 2 and
      4 and then slowly decreased to 33% of the baseline levels at day 14. With HEPA
      cleaner a significant reduction in airborne Fel d 1 was observed compared with
      the control sampling (GM 5.04-0.88 ng/m3 versus 3.79-1.56 ng/m3 at baseline and 8
      hours, active versus control group; p = 0.008). CONCLUSIONS: Airborne Fel d 1 was
      detectable in undisturbed conditions in all homes with cats and in almost a third
      of homes without cats. In houses with cats a significant proportion (23%) of
      airborne Fel d 1 was associated with small particles (< 4.7 microns diameter).
      Removal of the cat from the living room and bedroom areas of the home and the use
      of HEPA air cleaner reduced airborne levels of cat allergen in homes with cats,
      but the reduction following cat removal was not evenly spread across the particle
      size range.

PMID- 9577521
TI  - Comparison of the functional results of single lung transplantation for pulmonary
      fibrosis and chronic airway obstruction.
AB  - BACKGROUND: Single lung transplantation (SLT) is now a treatment option for
      patients with both pulmonary fibrosis and advanced chronic airway obstruction.
      Lung function after transplantation might be expected to be different in these
      two groups of patients because of the effect of the remaining native lung, but
      the implications of these differences have not been fully explored. METHODS: The
      functional results of a stable population of 20 patients (13 chronic airway
      obstruction, seven pulmonary fibrosis) after SLT with no evidence of obliterative
      bronchiolitis were analysed. The differences between the two populations in the
      interrelations between and determinants of total lung capacity (TLC),
      subdivisions of lung volume, airway function (spirometry, maximum expiratory flow
      volume curves, and moments analysis of the spirogram) respiratory mechanics (PV
      curves and maximal respiratory pressures), CO transfer factor (TLCO) and the
      distribution of perfusion, ventilation and volume of the transplanted and native
      lungs were compared. RESULTS: Total lung capacity after SLT (TLCpost) was normal
      in the patients with pulmonary fibrosis (mean (SE) 103.9 (6.9)% predicted) but
      remained significantly elevated in patients with airway obstruction (126.4
      (4.4)%. Forced expiratory volume in one second (FEV1) and vital capacity (VC)
      improved to similar values after SLT in both groups with a final VC of 76.8
      (5.9)% and 66.7 (3.9)% in patients with fibrosis and airway obstruction,
      respectively. Maximum expiratory flows were generally lower and moments analysis
      of the spirogram showed slower lung emptying with significantly greater second
      and third moments (alpha 2 and alpha 3) in patients with airway obstruction.
      Relative ventilation and perfusion of the transplanted lung were both greater in
      both populations but relative ventilation of the transplanted lung was
      significantly greater in patients treated for airway disease than in those with
      pulmonary fibrosis. TLCO was also significantly higher in patients who had
      received a transplant for chronic airway obstruction. CONCLUSIONS: These results
      suggest that differences in the functional results of SLT for airway disease and
      pulmonary fibrosis are relatively minor. In this series the native hyperinflated
      lung in chronic airway disease was not more disadvantageous to overall function
      than the native lung in pulmonary fibrosis. However, tests of lung function based
      on the terminal portion of the forced spirogram are likely to be less sensitive
      for the detection of obliterative bronchiolitis in patients who have received a
      transplant for advanced airway obstruction than in those with pulmonary fibrosis.

PMID- 9577522
TI  - Health effects of passive smoking. 4. Parental smoking, middle ear disease and
      adenotonsillectomy in children.
AB  - BACKGROUND: A systematic quantitative review was conducted of evidence relating
      parental smoking to acute otitis media, recurrent otitis media, middle ear
      effusion, and adenoidectomy and/or tonsillectomy. METHODS: Forty five relevant
      publications were identified after consideration of 692 articles selected by
      electronic search of the Embase and Medline databases using keywords relevant to
      passive smoking in children. The search was completed in April 1997 and
      identified 13 studies of acute otitis media, nine of recurrent otitis media, five
      of middle ear effusion, nine of glue ear surgery, and four of adenotonsillectomy.
      A quantitative meta-analysis was possible for all outcomes except acute otitis
      media, using random effects modelling where appropriate to pool odds ratios from
      each study. RESULTS: Evidence for middle ear disease is remarkably consistent,
      with pooled odds ratios if either parent smoked of 1.48 (95% CI 1.08 to 2.04) for
      recurrent otitis media, 1.38 (1.23 to 1.55) for middle ear effusion, and 1.21
      (0.95 to 1.53) for outpatient or inpatient referral for glue ear. Odds ratios for
      acute otitis media are in the range 1.0 to 1.6. No single study simultaneously
      addresses selection bias, information bias and confounding, but where these have
      been investigated or excluded in the design or analysis, the associations with
      parental smoking persist virtually unchanged. Large French and British studies
      are inconsistent with regard to the association of parental smoking and
      tonsillectomy. CONCLUSIONS: There is likely to be a causal relationship between
      parental smoking and both acute and chronic middle ear disease in children.

PMID- 9577524
TI  - Lung infections. 1. Role of bacteria in the pathogenesis and progression of acute
      and chronic lung infection.

PMID- 9577526
TI  - Tracheal botryomycosis in a patient with tracheopathia osteochondroplastica.
AB  - Tracheal botryomycosis has never been reported in the literature. A 68 year old
      man presented with progressive dyspnoea and an exophytic mass below the vocal
      cords was found by bronchoscopy. Pathological study of the mass showed tracheal
      botryomycosis probably associated with Peptostreptococcus spp infection. The
      patient was given intravenous penicillin for six weeks. Tracheal obstruction
      necessitated tracheal resection and the surgical specimen revealed typical
      findings of tracheopathia osteochondroplastica without residual lesions of
      botryomycosis.

PMID- 9577525
TI  - Allergen avoidance in the treatment of asthma and atopic disorders.

PMID- 9577527
TI  - Infection with feline Chlamydia psittaci.

PMID- 9577528
TI  - Adrenocortical activity in children.

PMID- 9577530
TI  - Home environment and asthma.

PMID- 9577529
TI  - Fenoterol and asthma deaths.

PMID- 9577531
TI  - The promise of youth.

PMID- 9577532
TI  - Teaching family medicine in urban St. Paul.

PMID- 9577533
TI  - HCMC reaches out from the inner city. Hennepin County Medical Center.

PMID- 9577534
TI  - Emergency docs in their element.

PMID- 9577535
TI  - G is for gangsta. Understanding gangs in Minnesota.

PMID- 9577536
TI  - President Clinton proposes Medicare user fees.

PMID- 9577537
TI  - Somali refugee health screening in Hennepin County.
AB  - Somalis are one of the newest refugee groups to settle in Minnesota, first
      arriving in 1993. The largest number of Somali refugees in Minnesota live in
      Hennepin County, which received 85% of the state's Somali refugees in 1996. In
      this population, tuberculosis, parasitic diseases, and malaria are of particular
      concern. In 1996 Somalis accounted for 27% of the foreign-born cases of
      tuberculosis in Minnesota. Before entering the United States, all refugees are
      given an overseas health assessment, which focuses on identifying conditions that
      might be contagious. The examination is limited and is valid for one year.
      Domestic refugee health assessment is very important, since it provides a
      comprehensive medical evaluation and treatment plan for health conditions that
      may interfere with successful resettlement.

PMID- 9577538
TI  - A community health assessment of a culturally diverse housing project in St.
      Paul.
AB  - A comprehensive community needs assessment was recently completed at Skyline
      Towers, a culturally diverse housing project in St. Paul. Eighty-one randomly
      selected residents were interviewed over a one-month period. This article
      outlines the process of conducting the assessment and describes the results from
      the health care and demographic sections of the survey. The assessment showed
      that two-thirds of the building residents were born outside the United States and
      that the Somali population in particular faces linguistic, financial, and
      cultural barriers that limit their access to health care.

PMID- 9577540
TI  - Childhood lead poisoning.

PMID- 9577539
TI  - Barriers to health care for immigrants and nonimmigrants: a comparative study.
AB  - A survey asked medical social workers and visiting public health nurses to
      identify health problems and to compare barriers to health care experienced by
      immigrants and nonimmigrants in the Twin Cities area. Respondents considered
      infectious diseases a more significant problem for immigrants; they saw alcohol
      and chemical dependency as more problematic for nonimmigrants. Survey respondents
      thought that both groups experienced many of the same logistical barriers,
      including inadequate insurance coverage, transportation, mental stress, time
      constraints, and distance to their health care facilities. They identified
      language barriers and the need for trained interpreters as barriers for
      immigrants only. The survey confirmed widely held assumptions that cultural
      barriers are more problematic for immigrants, although these barriers were also
      perceived for nonimmigrants. Participants identified 16 of 18 health services as
      more available for nonimmigrants. Emergency and obstetrical services are equally
      available to the two groups, according to survey respondents.

PMID- 9577541
TI  - Let the debate begin. But keep it civil.

PMID- 9577542
TI  - Activities that can affect your dental license.

PMID- 9577543
TI  - Is it time for national advertising? You decide.

PMID- 9577544
TI  - Plenty of blame to go around.

PMID- 9577545
TI  - Dental schools can't do it alone.

PMID- 9577546
TI  - Doesn't compute.

PMID- 9577547
TI  - Shedding light on lasers.

PMID- 9577548
TI  - Joseph Caruso is Bernard P. Tillis Award winner. There is reason to hope and
      organized dentistry provides it.

PMID- 9577549
TI  - The radiosurgical approach to biopsy.
AB  - The use of radiosurgery to remove a lesion for biopsy facilitates the time and
      effectiveness of the procedure. The hemostatic properties of the radiowave
      affords the practitioner a better field of visibility, enabling the procedure to
      be done in a safe, timely fashion.

PMID- 9577550
TI  - Distraction osteogenesis for the reconstruction of the temporomandibular joint.
AB  - Distraction osteogenesis is the technique of slow bone expansion across an
      osteotomy site. Most commonly used for orthopedic lengthening of the extremities,
      it is now being applied to the craniofacial skeleton, including treatment of
      facial asymmetries, micrognathias and mandibular discontinuity defects. The
      technique can also be applied for the reconstruction of a neo-condyle. Transport
      distraction osteogenesis may prove to be a treatment alternative for patients
      requiring condylar reconstruction.

PMID- 9577551
TI  - Management of facial fractures.
AB  - Dentistry has played an important role in the treatment of facial injuries. New
      imaging methods, expanded surgical approaches and improved biomaterials have
      brought about significant improvements in the outcomes. Excellent cosmetic and
      functional results have been made possible through early definitive intervention.

PMID- 9577552
TI  - TMD issues in patient with skeletal deformity of jaws.
AB  - Although there is little solid evidence that dental malocclusion directly results
      in significant TMJ problems, there appears to be strong correlation with
      malocclusions resulting from skeletal deformities. The highest correlation is
      generally noted in the patient with a deep bite or with asymmetry. Significant
      improvement can be anticipated with surgical correction of these deformities, but
      great care must be taken to properly diagnose the source of the deformity, and to
      use the correct technique, applied as atraumatically as possible.

PMID- 9577553
TI  - [Urinary tract infection: bacterial adhesin and biofilm formation].

PMID- 9577554
TI  - [Study of SV40-transformed cell lines from rat dorsolateral prostate--analysis of
      growth factors and their receptors in the epithelial cell line].
AB  - BACKGROUND: We transformed primary cultured epithelial cells of the rat
      dorsolateral prostate by Simian Virus 40 (SV 40) and established a stable
      epithelial cell line (PESVH). To examine whether this cell line is available for
      the fundamental research of prostatic diseases, investigation on the growth
      factors and their receptors of this cell line was made. METHOD: The [3H]
      thymidine uptake method was used to examine the influence for cell proliferation
      of epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), basic
      fibroblast growth factor (bFGF), keratinocyte growth factor (KGF), transforming
      growth factor (TGF)-alpha, TGF-beta 1 and androgens. The expression of mRNA for
      growth factors and their receptors was determined with Northern blot analysis.
      RESULT: DNA synthesis was increased to 2.1-fold of control by the addition of 100
      ng/ml EFG. The addition of aFGF (100 ng/ml), bFGF (100 ng/ml) and TGF-alpha (100
      ng/ml) tended to stimulate the DNA synthesis, but not significantly. The addition
      of KGF (0.1-100 ng/ml) did not influence on the DNA synthesis of PESVH. The
      addition of testosterone and 5 alpha-dihydrotestosterone (10(-10)-10(-6) M) did
      not influence on the DNA synthesis. Northern blot analysis showed expression of
      mRNA for TGF-alpha, TGF-beta 1, EGF receptor and TGF-beta receptor (type II) in
      PESVH cell. These expressions were not influenced by the addition of androgens.
      CONCLUSION: These findings suggested that PESVH cell could be used for one model
      of the androgen-independent prostatic cell.

PMID- 9577555
TI  - [Investigation of long-term follow up after endoscopic operation for
      vesicoureteral reflux].
AB  - BACKGROUND: Results with respect of the state of the infused agent and the cause
      of unsuccessful outcome were examined in patients who were followed for more than
      5 years after endoscopic surgery for vesicoureteral reflux (VUR). METHODS: Of 259
      ureters treated by TUI (Transurethral injection) after 1988, 41 ureters (29
      patients) that were followed for more than 5 years postoperatively were
      investigated. In all patients, teflon paste had been infused. The intervals
      between surgery and study enrollment ranged from 5 to 10 years, with a mean of
      5.1 years. RESULTS: After TUI was performed once, reflux disappeared in 30 (73%)
      of 41 ureters. The intervals between the detection of relapse and additional
      surgery ranged from 1 to 18 months, with a mean of 6.5 months. In 10 of 11
      ureters with relapse, relapse was detected within one year after the initial
      surgery. When the presence or absence of reflux was examined at the final
      evaluation, there was no relapse in 34 of 39 ureters, with a mean postoperative
      follow-up of 5.9 years. Teflon paste could be sufficiently confirmed in 34 of 39
      ureters excluding patients in whom TUI was changed to invasive surgery. However,
      this agent could not be confirmed in 5 ureters during follow-up. CONCLUSION:
      Teflon paste was not confirmed by bladder echo in any patient showing an
      unsuccessful outcome, suggesting that success or failure in this procedure
      depends on the persistence of paste.

PMID- 9577556
TI  - [Study on the relationship between tumour necrosis factor gene polymorphism and
      prognosis in the patients with renal cell carcinoma].
AB  - BACKGROUND: Clinical significance of polymorphism of tumour necrosis factor (TNF)
      genes encoded on the short arm of the 6th chromosome in the patients with renal
      cell carcinoma (RCC) has not been evaluated well so far. We studied on the TNF
      genes polymorphism of RCC focusing on the relationship between the genetic
      polymorphism and the prognosis. METHODS: The subjects were seventy-three patients
      with RCC treated at our hospitals during the past 20 years. The genomic DNA was
      examined by the methods of polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) from frozen peripheral blood of these patients. The items
      examined were the genetic polymorphisms of TNF-alpha (alpha 1, alpha 2) and TNF
      beta (beta 1, beta 2), and we tried to study on the prognostic outcome of RCC
      based upon each zygote of TNF. RESULTS: 1) The proportion of TNF-alpha and TNF
      beta polymorphisms: We observed TNF-alpha 1/1 homozygote in 71 patients (97.3%).
      As to TNF-beta polymorphism, we observed TNF-beta 2/2 homozygote in 33 patients
      (45.2%), TNF-beta 1/2 heterozygote in 31 (42.5%) and TNF-beta 1/1 homozygote in 9
      (12.3%). The proportion of TNF-beta polymorphism was almost the same as that of
      healthy Japanese. 2) PROGNOSIS: Regarding the 17-year survival, all patients with
      TNF-beta 1/1 homozygote were alive, and we observed a significantly favourable
      prognosis in the patients with TNF-beta 1/1 homozygote compared with other
      zygotes of TNF-beta polymorphism. The reasons for these favourable prognosis were
      thought that the patients with TNF-beta 1/1 homozygote showed much lower stage
      and/or grade than those of other zygotes. CONCLUSION: We conclude that the TNF
      beta gene polymorphism is a useful marker for understanding the prognosis of RCC
      and a part of cellular immunity related to the tumour and its host.

PMID- 9577557
TI  - [Combination therapy of daily intramuscular injection of interferon-alpha and
      oral administration of fluorouracil for advanced renal cell carcinoma].
AB  - BACKGROUND: To achieve optimum drug delivery of Interferon-alpha in treatment of
      renal cell carcinoma, a regimen consisting of its daily intramuscular
      administration, in combination with oral fluorouracil, was designed and carried
      out. Its efficacy is examined retrospectively. METHODS: In our department 7
      patients with disseminated renal cell carcinoma were treated with daily
      intramuscular injection of interferon-alpha (3 x 10(6) IU) and daily oral
      administration of fluorouracil. All patient was nehprectomized before initiation
      of the regimen. RESULTS: Two patients achieved complete, and three patients
      achieved partial response radiographically (Overall response rate 71%).
      Metastatic sites of responders were lung (4) and pleura (2). The time required
      until response was 3.9 (median 5.4) months. In two responders, new lesions
      appeared in other organs despite durable response in initial pulmonary metastatic
      sites. There were two no-responders, one patient is alive with stable disease and
      the other patient died for progression of the disease. In all, two patients died
      of disease, one died for other cause, one surviving without evidence of disease,
      and three are surviving with disease. No significant side effect was noted in
      these seven patients. CONCLUSIONS: This regimen can be carried out on outpatient
      basis and considerable response can be expected for pulmonary and pleural
      lesions.

PMID- 9577558
TI  - [Studies of prostate-specific antigen (PSA) immunoassays--differences in
      characteristic of immunoreactivity and reference materials among the kits].
AB  - PURPOSE: We conducted this study to examine differences in characteristics of
      immunoreactivity for free PSA and alpha(1)-antichymotrypsin complex PSA (ACT-PSA)
      as well as in compositions and concentrations of PSA reference materials among
      commercially available PSA kits. METHODS: Fractionated serum samples using a
      Sephacryl S-200 column were measured by Tandem-R, Delfia-PSA, Ab bead PSA, ACS
      PSA, Markit-M and gamma-seminoprotein (gamma-Sm) kits. The calibrators of Tandem
      R, Delfia-PSA, Ab bead PSA and Markit-M were fractionated by the same method and
      measured by Tandem-R. The calibrators of Delfia-PSA, Ab bead PSA and Markit-M and
      control serums of ACS-PSA were measured by Tandem-R. RESULTS: Although the
      characteristic of immunoreactivity of Tandem-R, Delfia-PSA, and Ab bead PSA were
      found to be similar, they were not shown identical. ACS-PSA was proved to
      recognize free PSA greater than above three PSA kits, while Markit-M could
      scarcely detect free PSA. gamma-Sm recognized only free PSA. The calibrators of
      Tandem-R, Delfia-PSA, Ab bead PSA and Markit-M were proved to be only free PSA.
      The linear correlation was obtained between Tandem-R and Delfia-PSA or Ab bead
      PSA or Markit-M. The ratio of Delfia-PSA to Tandem-R, Ab bead PSA to Tandem-R and
      Markit-M to Tandem-R was 0.66, 0.93 and 2.2, respectively. With regard to
      relation of ACS-PSA and Tandem-R, two ratios of 0.22 and 0.25 were obtained
      between the two kits according to the different concentrations of control sera.
      CONCLUSION: The present studies suggest that the difference in PSA values among
      the commercial PSA kits results from (1) different characteristics of
      immunoreactivity for ACT-PSA and free PSA among PSA kits, (2) compositions of PSA
      calibrators among the kits, and (3) different concentrations of PSA calibrators
      among the kits.

PMID- 9577559
TI  - [Changes in blood polyamine levels following chemotherapy in patients with
      invasive urinary bladder carcinoma].
AB  - BACKGROUND: Polyamines are recognized as cell growth factors. We attempted to
      determine whether blood polyamines are useful biochemical makers for monitoring
      the efficacy of the chemotherapy on bladder tumors. METHODS: The blood
      concentrations of three polyamines, diamine, spermidine and spermine, were
      determined in 31 patients with invasive urinary bladder carcinoma, following
      chemotherapy with cisplatin, methotrexate and pirarubicin. Clinical response was
      evaluated by CT after 3 weeks. In 26 patients who underwent subsequent surgical
      therapy, the effectiveness of the chemotherapy were histopathologically evaluated
      by a pathologist according to the response criteria for bladder cancer treatment.
      RESULTS: Mean regression rate in the size of the tumor after the chemotherapy was
      40.8%. Of 31 patients, clinical CR was observed in 2, PR in 11, and NC in 18. Of
      26 patients who were histopathologically evaluated, grade 3 was observed in 5,
      grade 2 in 4, grade 1b in 4, grade 1a in 12, and grade 0 in 1. One week after
      chemotherapy, the levels of spermine and total polyamine in the patients with CR
      and PR were significantly lower than those in the patients with NC. Similarly one
      week after chemotherapy, the levels of spermine and total polyamine in the
      patients with grade 3 and grade 2 were significantly lower than those in the
      patients with grade 1b, grade 1a and grade 0. CONCLUSION: The study suggested
      that the levels of blood polyamines could be used as biochemical markers for
      monitoring the efficacy of the chemotherapy on bladder tumors.

PMID- 9577560
TI  - [A case of polyorchidism with embryonal carcinoma].
AB  - Polyorchidism is a rare anomaly with approximately 70 cases reported in the
      literature. We reported a case of polyorchidism with embryonal carcinoma, the
      first case, in one of 4 testes. Polyorchidism with malignancy had been reported
      in 5 cases and bilateral polyorchidism in 3 cases. Authors have not been
      clarified whether the incidence of malignancy in polyorchidism is high or low.
      But we have to treat the patients with polyorchidism carefully, because
      polyorchidism is highly associated with cryptorchidism.

PMID- 9577562
TI  - [The 82nd congress of the Medico-Legal Society of Japan. Tokyo, Japan. April 15
      17, 1998. Abstracts].

PMID- 9577561
TI  - [Subcapsular hematoma of the liver after extracorporeal shock wave lithotripsy].
AB  - We experienced a case of a hepatic subcapsular hematoma after extracorporeal
      shock wave lithotripsy (ESWL) for a right renal stone. To our knowledge this
      presentation is the second case in the Japanese literature. A 63-year-old female
      with a right renal stone received 2,800 shots of 14.0 kilo-volts shockwave with
      Sonolith 3,000. Preoperative examination of the blood disclosed no abnormalities
      in the coagulating system except slight reduction of platelet count and slight
      impairment of liver function. Postoperative routine ultrasound echograms revealed
      a hepatic subcapsular hematoma although she had no symptom. The size of the
      hematoma measured 11.0 x 5.0 cm in computed tomograms (CT). She was carefully
      observed without any treatments because the hematoma did not increase in size. CT
      scans 6 months after the ESWL treatment demonstrated neither hematoma nor masses
      in the liver. As a complication of ESWL for urolithiasis a hepatic subcapsular
      hematoma is very rare. We herein presented the case and discussed the
      complications of ESWL briefly in the literature.

PMID- 9577563
TI  - [The 57th annual meeting of the Japan Radiological Society. Kobe, Japan. April 9
      11, 1998. Abstracts].

PMID- 9577564
TI  - [Recent findings on etiological mechanism of autoimmune diseases].

PMID- 9577565
TI  - [Physiopathology and therapy of rheumatoid arthritis].

PMID- 9577566
TI  - [Physiopathology and therapy of systemic lupus erythematosus].

PMID- 9577567
TI  - [Physiopathology and therapy of progressive systemic sclerosis].

PMID- 9577568
TI  - [Physiopathology and therapy of adult onset Still's disease].

PMID- 9577569
TI  - [Physiopathology and therapy of Behcet's syndrome].

PMID- 9577570
TI  - [Recent findings on mechanism of allergy].

PMID- 9577571
TI  - [Treatment of bronchial asthma].

PMID- 9577572
TI  - [Hypersensitivity pneumonitis].

PMID- 9577573
TI  - [Physiopathology and diagnosis of secondary hypertension--gene diagnosis of
      hypertension].

PMID- 9577574
TI  - [Diagnosis, therapy and nutrition management of osteoporosis].

PMID- 9577575
TI  - [Diagnosis and therapy of multiple endocrine neoplasia].

PMID- 9577576
TI  - [Diagnosis and therapy of antiphospholipid antibody syndrome].

PMID- 9577577
TI  - [Extra-articular symptoms and treatment of rheumatoid arthritis].

PMID- 9577578
TI  - [Etiology and therapy of cholesterol cholelithiasis].

PMID- 9577579
TI  - [Long-term prognosis of chronic hepatitis C--special reference to interferon
      therapy].

PMID- 9577580
TI  - [Diagnosis and therapy of ++Helicobacter pylori infections].

PMID- 9577581
TI  - [Current status of nervous system virus infections].

PMID- 9577582
TI  - [Trends in diagnosis and therapy of hereditary neurodegenerative diseases].

PMID- 9577583
TI  - [Physiopathology and therapy of vertigo or dizziness due to cerebrovascular
      disorders].

PMID- 9577584
TI  - [Diagnosis and therapy of chronic myeloproliferative disorders].

PMID- 9577585
TI  - [Diagnosis and therapy of anemia in the aged].

PMID- 9577586
TI  - [Countermeasures for respiratory failure of chronic obstructive lung disease].

PMID- 9577587
TI  - [Current status on the treatment of asthma--special reference to anti
      inflammatory drug therapy].

PMID- 9577588
TI  - [Recent status and changes in respiratory tract infections].

PMID- 9577589
TI  - [Sexually transmitted diseases].

PMID- 9577590
TI  - [Cholesterol-reducing therapy of arteriosclerosis].

PMID- 9577591
TI  - [Therapy and physiopathology of acute coronary syndrome].

PMID- 9577592
TI  - [Drug therapy of cardiac failure].

PMID- 9577593
TI  - [Glomerulonephritis and immunology].

PMID- 9577594
TI  - [Renal tubular acidosis].

PMID- 9577595
TI  - [New application of ultrasound imaging using contrast agent].
AB  - Recently, various ultrasound contrast agent have been developed all over the
      world. This paper reviewed recent development of some contrast agent and clinical
      application of new imaging using contrast agent (Enhanced color Doppler Imaging,
      Harmonic Imaging, Flash Echo Imaging and Loss of Correlation Imaging). These new
      methods are easily feasible with a clinical ultrasound diagnosis machine for
      evaluating further information, for example, slow or deeply located lesion's
      blood flow, furthermore tissue perfusion. Contrast enhanced ultrasound imaging
      such as Harmonic imaging is enable to evaluate tissue function.

PMID- 9577596
TI  - [Ultrasound contrast agents--newly developed agents and their clinical utility].
AB  - Recently many ultrasound contrast agents have been developed. Vascular and
      parenchymal enhancement of the organs such as liver and myocardium is obtained by
      intravenous injection of microbubble agents. They can survive after recirculation
      through the pulmonary capillary beds and under changes in vascular pressure.
      Several modalities of ultrasound imaging have been developed for effective
      enhancement. The harmonic imaging system is the most effective to depict contrast
      enhancement because of subtraction effect using retrieval of harmonic components
      from interaction microbubbles and ultrasound transmission. This is originated
      from resonance and destruction of microbubbles under ultrasound exposure.

PMID- 9577597
TI  - [Recent progress of the medical ultrasound contrast imaging technology].
AB  - Development and research on the ultrasound contrast agents is becoming a very
      important topic in the field of diagnostic ultrasound. The reason is that
      ultrasound contrast agents have an enormous potential clinical applications in
      cardiology, neurology and in vascular medicine. In this report, the problems
      encountered, the potential use and the future development of microbubble-type
      ultrasound contrast agents are discussed in detail. In coming years, it is
      expected that researches will concentrate on the development of long-lifetime and
      low-toxicity microbubbles contrast agents to overcome the problems that were
      encountered. After then, by making use of both the linear and non-linear
      properties of ultrasound contrast agents, the development of new generation
      ultrasound diagnostic equipment can be expected in the next decade.

PMID- 9577598
TI  - [Discussion on the technical terms in enhancement of ultrasonography using
      contrast agents].
AB  - Recent advances in enhancement of ultrasonography (US) using contrast agents have
      been extended rapidly. However, there was no exact technical term which was
      received much recognition. The Japan society of ultrasonics in medicine carried
      out a questionnaire to 110 institutions in Japan and a symposium for the
      technical terms of contrast enhancement of US in the abdominal field. Based on
      the results of the questionnaire and the symposium, "Enhanced US" seems to be a
      most suitable term for the US using contrast agents. The terms of contrast
      effects of enhanced US for analysis are also discussed in this article.

PMID- 9577599
TI  - [Properties of gas (CO2) microbubbles made by hand agitation and it's contrast
      enhancing effect].
AB  - The property of gas (CO2) microbubbles made by hand agitation and it's contrast
      enhancing effect of abdominal organs on gray scale ultrasound are here described.
      The size of microbubbles of CO2 gas adequately prepared with 5% human serum
      albumin was nearly 23 microns in mean diameter. However, the size and the density
      of gas microbubbles are affected with many factors, including mixing times,
      volume ratio of gas and liquid and the species of gas and liquid. On the other
      hand, contrast enhancing effect is determined by the size and the density of gas
      microbubbles. For the adequate evaluation of contrast enhancing effect of
      abdominal tumors by enhanced ultrasonography, the property of gas microbubbles
      described as above should be carefully considered.

PMID- 9577600
TI  - [Ultrasound scattering properties of Albunex microspheres].
AB  - In Japan, clinical and basic investigations of Albunex were started from 1989,
      and was firstly approved by the government as a commercially available contrast
      agent for the cardiovascular disorders. Although it has recently evacuated from
      the market, its acoustic properties proven by the many investigators were
      valuable for preparation of the second generation of contrast agents. Therefore,
      we summarized our data of the ultrasonic properties of Albunex both in vitro and
      experimental dog studies using RF signals. In conclusion, Albunex was a extremely
      sensitive blood flow tracer in evaluating intracardiac blood flow as well as
      intramyocardial perfusion.

PMID- 9577601
TI  - [Levovist].
AB  - SH/TA-508 (Levovist) is agglomerates of microparticles consisting of galactose
      (99.9%) and palmitic acid (0.1%), and the active entity is the microbubbles
      stabilized by palmitic acid which covers the bubbles. SH/TA-508 micro-bubbles are
      stable under high-pressure condition and they circulate the whole body for
      several minutes along with blood flow after the intravenous injection. The left
      sided cardiac cavities and arteries are clearly opacified by using this contrast
      agent and the Doppler signals from the mitral, aortic and pulmonic vein are also
      enhanced significantly. Also microcirculating flow image of the liver, kidney and
      other organs are well enhanced in the clinical studies. SH/TA-508 improves the
      capability of ultrasound diagnosis.

PMID- 9577602
TI  - [Harmonic imaging].
AB  - Microbubbles undergoing resonant oscillation in a diagnostic ultrasound field can
      be induced to exhibit nonlinear motion. The ultrasound signals emitted by such
      microbubbles contain strong harmonics at twice the frequency of the transmitted
      ultrasound beam. Second harmonic imaging improves tissue-agent contrast. The
      usefulness of second harmonic imaging was evaluated in vivo experiments. The
      hepatic parenchyma was clearly enhanced in dogs. Second harmonic imaging can be
      expected to expand the capabilities of diagnostic ultrasound systems in
      visualizing tissue perfusion.

PMID- 9577603
TI  - [Flash echo imaging].
AB  - Ultrasound transmission sometimes limits the lifetime of microbubble-based
      contrast agents. At this time, a very large echo signal (like a flash) is
      obtained for the initial transmission of the ultrasound after several seconds'
      suspension. Flash Echo Imaging (FEI) is a new technique which uses the signals of
      the bubble's collapse. This paper explains a principle of FEI and functions of
      the FEI's application for ultrasound diagnostic system. It is also shown that
      perfusion of the tissue can be visualized by using FEI methods.

PMID- 9577604
TI  - [Review: the overviews of contrast echocardiography in cardiovascular disorders].
AB  - The contrast echocardiography used to be applied for the diagnosis of congenital
      heart diseases, analysis of right side heart hemodynamics, and the evaluation of
      peripheral blood flow profiles. Recently, myocardial contrast echocardiography is
      evoked for estimating regional coronary blood flow as a parallel procedure of
      interventional therapy for ischemic patients. Advanced technology such as
      harmonic imaging, rf signal processing and digital storage of the data are
      extremely supportive for the quantitative evaluation of myocardial blood flow. In
      addition, new contrast agents which enable interpretation of myocardial contrast
      could be administered by peripheral injection.

PMID- 9577605
TI  - [Myocardial contrast echocardiography as a potential diagnostic tool for the
      assessment of myocardial perfusion].
AB  - Myocardial contrast echocardiography (MCE) visualizes the spatial distribution of
      myocardial blood flow with the injection of microbubbles into the coronary
      artery. With MCE, we can easily assess the perfusion territory of the coronary
      artery and collateral circulation as positive contrast area and the risk area as
      contrast defects. In patients with acute myocardial infarction (AMI), we can
      assess the success of coronary reperfusion at the microcirculation level. Some
      patients with AMI manifest sizable contrast defects after reperfusion, called no
      reflow phenomenon. This phenomenon identifies patients with poor functional and
      clinical outcomes among reperfused patients. Thus, MCE provided an useful method
      of assessing myocardial perfusion dynamics as well as myocardial viability in
      clinical setting.

PMID- 9577606
TI  - [Assessment of myocardial perfusion with second harmonic imaging--using
      intravenous injection of Albunex and Levovist].
AB  - The objection of this study was to determine whether a method of harmonic imaging
      could improve the myocardial contrast after injection of Albunex and Levovist.
      Two dogs were imaged harmonic mode from transdiaphragm approach (transmit at 2.5
      MHz and received at 5.0 MHz). Albunex (0.22 ml/kg) and Levovist (400 mg/ml x 2
      ml) was injected intravenously for each dog. Venous injection of Albunex coupled
      with harmonic imaging produced only coronary flow. Venous injection of Levovist
      coupled with harmonic imaging produced myocardial opacification. It is possible
      that venous injection of Levovist coupled with harmonic imaging method will also
      useful in studying myocardial perfusion.

PMID- 9577607
TI  - [Experimental study on efficacy of myocardial opacification owing to difference
      of echocardiographic contrast agents].
AB  - We studied on opacified duration and concentration of the opacification of the
      contrast agents. METHOD: The original contrast mediums are Albunex, 5% human
      albumin and Hexabrix. The used contrast agents were made by sonication of the
      original medium. Two dimensional echocardiograms were recorded in short axis at
      papillary muscle level. The evaluation of the opacified duration and the
      concentration of the opacification were practiced by visual observation and image
      analyzer. RESULTS AND CONCLUSION: 1) There were no difference among Albunex,
      sonicated 5% human albumin and sonicated Hexabrix in the myocardial opacification
      in the visual observation. 2) The opacified duration lasted longest in sonicated
      5% human albumin.

PMID- 9577608
TI  - [Myocardial contrast echocardiography from peripheral venous injection: the
      potential for detection of myocardial perfusion abnormality].
AB  - Myocardial contrast echocardiography is a useful method for clinical evaluation
      of myocardial perfusion abnormality in ischemic heart disease. However, this
      method has a limitation in selection of patients because it is necessary to
      inject the contrast agent directly into the coronary artery in a catheterization
      room to obtain the image of myocardial opacification. Recently several echo
      contrast agents that have the potential for myocardial opacification after
      intravenous injection have been developed. These agents consist of
      perfluorocarbon gas filled-microbubble coated by a stabilizing surfactant. It's
      persistence is longer in air filled-microbubble such as Albunex. Safety of
      contrast agent and highly efficacy for myocardial opacification, no significant
      changes in parameters of cardiopulmonary function and hemodynamics are reported
      both in animal and human studies. In future contrast myocardial echocardiography
      with intravenous injection offers the potential for reliable and noninvasive
      assessment of perfusion in myocardial infarction before and after therapeutic
      interventions.

PMID- 9577609
TI  - [Contrast enhancement using the triggered imaging].
AB  - Triggered imaging has been introduced as a practical method to improve contrast
      echo enhancement by T.R. Porter, Nebraska, U.S.A. in 1995. It requires a simple
      instrumentation, ECG or internal timer, for intermittent ultrasound imaging that
      reduces contrast attenuation due to ultrasound exposure. Currently, a clear
      myocardial contrast echo done by intravenous injection of contrast agent has
      become a common result when the latest generation agents, machines and the new
      methods are available. Contrast echocardiography is expected to be able to
      evaluate myocardial perfusion for future direction.

PMID- 9577610
TI  - [Assessment of left ventricular volume by contrast echocardiography].
AB  - Two-dimensional echocardiography for measuring left ventricular volumes usually
      gives volumes that are smaller than those determined with left ventriculography.
      This is due to less optimal image quality since manual tracing of endocardial
      borders requires still frames. Intravenous injection of echocontrast agent
      (Albunex) improve endocardial border recognition and therefore left ventricular
      volume measurements become more accurate. It is reported that contrast
      echocardiography significantly improves the correlation of echocardiographic left
      ventricular volume measurement with that of left ventriculography. From this
      points of view, contrast echocardiography is useful for the determination of left
      ventricular volumes in clinical settings.

PMID- 9577611
TI  - [The classification and analysis of the blood pathway in left ventricular cavity
      observed by left ventricular contrast echocardiography].
AB  - We can observe and analyse the blood pathway in left ventricular cavity by
      contrast echocardiography using sonicated albumin, because it can be through the
      pulmonary capillaries. I. The observational classification of the blood pathway
      in left ventricular cavity. Group I: The contrast medium comes to the apex
      directly from the mitral orifice. Group II: The contrast medium comes to the apex
      along the posterior wall forming the spiral flow and turns back to the outflow
      tract. Group III: The contrast medium is found like a fireworks only at the apex.
      II. The factors associated with the blood pathway in left ventricular cavity. 1.
      Abnormality of left ventricular wall motion, 2. The form of left ventricular
      cavity, 3. Early diastolic peak velocity of the transmitral flow, 4. A/E, 5. Left
      ventricular function.

PMID- 9577612
TI  - [Apical filling abnormality in patients with heart failure assessed with contrast
      echocardiography using venous injection of Albunex].
AB  - Contrast echocardiography by venous injection of Albunex was used to visualize
      apical filling abnormality in patients with heart failure. 1. Contrast
      echocardiography was serially performed in 24 patients with acute anterior
      myocardial infarction. Wall motion of the infarct region was better at any stage
      in patients without apical filling abnormality than in patients with that.
      Improvement of filling abnormality was observed prior to that of wall motion
      abnormality. 2. Influence of tachycardia was assessed on apical filling in 20
      patients with old myocardial infarction during rapid atrial pacing. Stress
      contrast echocardiography evidenced that tachycardia deteriorates apical filling
      abnormality in patients with chronic heart failure. 3. The effect of amrinone on
      apical filling was assessed in 60 patients with chronic anterior myocardial
      infarction. Apical filling abnormality improved in 46% of patients after amrinone
      infusion. The improvement of apical filling abnormality was closely related to
      the reduction of preload and improvement of asynergy in the infarct area after
      amrinone. Both adjunctive therapy and anticoagulant therapy should be considered
      if apical filling abnormalities are observed by contrast echocardiography.

PMID- 9577613
TI  - [Clinical usefulness of contrast-enhanced intracoronary ultrasound (ICUS) and
      evaluation of suitable contrast agents for ICUS].
AB  - It is sometimes difficult to visualize the luminal borders of the vessel even by
      intracoronary ultrasound (ICUS), especially after coronary intervention. In this
      study, we evaluated the potential for improving visualization at intervention
      sites using contrast-enhanced ICUS and the suitable contrast agents for this
      procedure in humans. In 37 patients, ICUS (30 MHz) was performed with
      intracoronary injection (3 ml) of 7 different contrast preparations and without
      the contrast agents (control) after coronary intervention. The contrast agents
      used were as follows: saline solution, standard iomeprol, standard ioxaglate,
      sonicated iomeprol, sonicated ioxaglate, 50% Albunex, and 100% Albunex. Vessel
      wall delineation, contrast homogeneity (Grade 0-3), peak contrast intensity and
      shadowing were examined. Homogeneous and complete opacification of the vessel
      lumen and false lumen was observed with sonicated ioxaglate, 50% and 100%
      Albunex. Shadowing was not observed at all with sonicated ioxaglate and was
      uncommon with 50% Albunex, whereas 100% Albunex caused shadowing in all cases.
      The coronary delineation rate with the other contrast agents was only 50-70 %,
      and the homogeneity and peak intensity were relatively low. Thus, sonicated
      ioxaglate and 50 % Albunex both achieved good visualization, but the former is
      cheaper, stable and takes shorter to prepare. Large dissection in 5 patients were
      found by contrast-enhanced ICUS' whereas they were not detected by coronary
      angiography. All of them needed additional interventional therapy due to the
      results of contrast-enhanced ICUS. In conclusion, contrast-enhanced ICUS is
      useful for evaluation of the results by intervention therapy, and of the agents
      we studied sonicated ioxaglate is best for contrast-enhanced ICUS.

PMID- 9577614
TI  - [Transarterial enhanced ultrasonography examination of hepatocellular carcinoma
      using CO2].
AB  - The findings of enhanced ultrasonography under the injection of microbubbles of
      carbon dioxide into a hepatic artery (CO2-US) were evaluated in the patients with
      hepatocellular carcinoma (HCC). They were as follows. Most nodules showed early
      (within 3 seconds) stronger enhancement compared to the surrounding hepatic
      parenchyma, remaining the enhancing effects more longer than the surround. A few
      nodule showed isoenhance or nonenhancement. However, metastatic cancer of the
      liver often showed the early enhancement only at the edge of tumor. In hepatic
      hemangioma, only the spotty enhancement in the tumor and or the later (later than
      4 seconds) enhancement at the edge of tumor was showed. The hyperenhanced mass
      was detected more often in a larger HCC and revealed to be a relatively poorly
      differentiated HCC with the capsule formation.

PMID- 9577615
TI  - [Diagnosis of small hepatocellular carcinoma by US angiography with intraarterial
      CO2 microbubbles imaging].
AB  - US angiography, enhanced with intraarterial CO2 microbubbles imaging, documented
      40 nodules of hepatocellular carcinoma (HCC) lesser than 20 mm in diameter in 34
      patients, which were convinced histopathologically. As to the imaging acuity of
      arterial vascularity in nodules, US angiography was compared with DSA and US
      color angio. The detection of arterial vascularity was possible in 34 (85.0%) of
      40 nodules by US angiography, 26 (65.0%) by DSA, and 28 (70.0 %) by US color
      angio. US angiography was available for detection of HCC, particularly with small
      HCC lesser than 20 mm in size.

PMID- 9577616
TI  - [The diagnosis of the early stage of hepatocellular carcinoma by US-angiography
      with intraarterial Albunex (sonicated serum albumin) infusion].
AB  - Contrast-enhanced ultrasonography (arterial infusion) has been clinically
      established as a qualitative diagnosis imaging tool for hepatocellular carcinoma
      (HCC). Contrast-enhanced ultrasonography (CEUS) was performed after of Albunex
      (sonicated serum albumin) or Carbon Dioxide (CO2) microbubble by hand, into the
      hepatic artery as a diagnostic modality for the early HCC. Here, we discussed the
      diagnosis of the early HCC by CEUS using Albunex as a contrast medium. Briefly, a
      diagnosis of the early HCC was made CEUS examination of the hemodynamics of the
      arteries showed a hypovascular pattern. And tumor size was under 20 mm in
      diameter, the histopathologic examination was essential to reach a final
      diagnosis, well-differentiated HCC.

PMID- 9577617
TI  - [Contrast enhanced color Doppler sonogram of liver tumors: a color-filled pattern
      in the late phase].
AB  - In the present report, a "color-filled pattern", the late phase effect in the
      intra-venous contrast enhanced color Doppler sonography is introduced, using
      SH/TA-508 as the contrast agent. This pattern is defined as an image of a tumor
      area filled with color in contrast to the surrounding liver. After contrast
      enhancement, the detectability of a "feeding artery" increased. And also "color
      filled pattern" appeared in 14 of the 21 hepatocellular carcinomas but none of
      the nine other liver tumors. In conclusion, contrast enhancement increases the
      detectability of a "feeding artery" and improves the sensitivity for HCC with
      color Doppler sonography. A "color-filled pattern" is also effective in the
      diagnosis of HCC because it requires no technical skill and shows high
      specificity.

PMID- 9577618
TI  - [Enhanced color flow findings in small hepatocellular carcinoma].
AB  - Features of enhanced color flow images of small hepatocellular carcinoma (HCC)
      were studied to elucidate their usefulness in evaluating tumor hemodynamics.
      Enhanced color Doppler using the contrast agent "SH/TA508" was performed on 16
      patients, 13 with HCC, 1 with regenerative nodule, and 2 with hemangiomas, in
      whom the size of the tumor were smaller than 30 mm. Enhanced color flow
      appearance was compared with angiographic findings. Significant improvement in
      the detection of color flow signals was obtained in small HCC using SH/TA508,
      from 33% in pre-contrast to 92% in post-contrast (p < 0.005). Three patterns of
      enhanced color flow images, which were related to the angiographic findings, were
      observed. Enhanced color flow imaging promises to be a useful method for
      evaluating tumor vascularity noninvasively, and to contribute to the elucidation
      of the hemodynamics in liver tumor.

PMID- 9577619
TI  - [Evaluation of blood flows inside hepatic tumors using color Doppler echography
      with galactose-based intravenous contrast medium "SH/TA 508" administration].
AB  - The purpose of this study is to evaluate hemodynamic characteristics of various
      hepatic tumors using color Doppler echography administered galactose-based
      intravenous contrast medium "SH/TA 508 (Levovist)". Subject were 9 cases of
      hepatocellular carcinomas, 5 cases of metastatic liver tumors and a case of
      hemangioma. We evaluated the characteristics of blood flows inside various
      hepatic tumors, and also evaluated the first pass through the hepatic tumors
      during administration of Levovist. The strongly pulsatile branched blood flows
      inside tumor and the slow-increased and plateau patterns were observed in the all
      cases of hepatocellular carcinomas, the weakly pulsatile blood flows surrounding
      tumor and the rapid-increased and slow-decreased patterns were observed in the
      cases of metastatic liver tumors, and the continuous blood streams in the margin
      of tumor and the slow-increased and slow-decreased pattern were observed in the
      case of hemangioma. These findings were characteristic in various hepatic tumors,
      and color Doppler echography enhanced by Levovist was very useful to distinguish
      hepatic tumors.

PMID- 9577620
TI  - [Sonographic depiction of woodchuck hepatomas using intravenously injected
      contrast agents].
AB  - Intravenously injected ultrasonic contrast agents have improved sonographic
      visualization of blood flow. On enhanced color Doppler sonography using Levovist
      (Schering AG, Germany) and FS069 (Molecular Biosystems, USA), minute tumor blood
      flow in woodchuck hepatoma was clearly demonstrated as vascular flow around and
      within the tumors. Furthermore, on enhanced gray scale sonography using FS069,
      parenchymal flow was demonstrated as sonographic "tumor stain". However, larger
      doses of the agent provided shadowing that disturbed sonographic evaluation of
      deeper portions of the liver. With advances of second harmonic imaging, it may be
      possible to evaluate only blood perfusion in that it eliminates the signals of
      fundamental frequency.

PMID- 9577621
TI  - [Contrast-enhanced power Doppler imaging of the liver--preliminary animal study].
AB  - PURPOSE: To evaluate efficacy of contrast-enhanced power Doppler imaging of the
      liver. MATERIALS AND METHODS: We administered two kinds of contrast agents, SHU
      508 (Schering AG, Germany) and FS069 (MBI, USA), intravenously to woodchucks with
      hepatocellular carcinomas. Power Doppler imaging of the liver was performed. To
      obtain minute hemodynamic information of the liver, we tried continuous infusion
      of contrast agents and flash echo mode (intermittent scanning) on power Doppler
      imaging. RESULTS: When we administered continuously contrast agents, the
      enhancement increased gradually and lasted until the end of the infusion. To
      compare with bolus injection, we were able to detect blood flow of the liver more
      clearly and easily without saturation artifacts. On power Doppler flash echo
      imaging of three or five seconds suspension, signals from only arterial flow were
      obtained. In comparison on seven seconds suspension imaging, signals from both
      arterial and portal flow were obtained. With flash echo mode, we could acquire
      the information of blood perfusion to depict the signals from eliminated
      microbubbles. CONCLUSION: With continuous infusion and flash echo mode on
      contrast-enhanced power Doppler imaging, we could get more detailed information
      of blood flow and perfusion of the liver. This method is expected to be useful
      for the diagnosis of liver tumor in clinical settings.

PMID- 9577622
TI  - [Transcatheter arterial embolization of hepatocellular carcinoma using CO2-US].
AB  - Enhanced ultrasonography under the injection of microbubbles of carbon dioxide
      into the hepatic artery (CO2-US) contributed to the treatment of hepatocellular
      carcinoma in the selection of indication of transcatheter arterial embolization
      (TAE). Judging from the accumulation of the lipiodol after TAE with the
      combination of lipiodol, TAE was thought to be effective in the tumor which was
      enhanced by CO2 microbubbles more strongly and the enhancement was prolonged more
      longer compared to the surrounding parenchyma, even the tumor had no tumor
      staining on the hepatic angiography. In none of the tumor which had no
      enhancement, TAE was effective. In most of the tumor with isoenhancement compared
      with surrounding parenchyma TAE was not effective.

PMID- 9577623
TI  - [Usefulness of enhanced US by CO2 microbubbles for segmental-subsegmental TAE for
      hepatocellular carcinoma].
AB  - Enhanced US by intraarterial infusion of CO2 microbubbles is useful for segmental
      to subsegmental TAE of hepatocellular carcinoma for several reasons. First, we
      can obtain better recognition of the tumor stain of hepatocellular carcinoma
      which is even faint on DSA. Secondly, we can recognize the co-relation between
      tumor stain and its related segment or subsegment well. Therefore, subsegmental
      or segmental TAE can be performed easily and precisely using enhanced US by CO2
      microbubbles. We noted the bigger advantage of enhanced US by CO2 microbubbles
      especially in the repeated treated cases of TAE for hepatocellular carcinoma.

PMID- 9577625
TI  - [Clinical diagnosis of pancreato-biliary lesions by ultrasound angiography with
      intra-arterial infusion of carbon dioxide microbubbles].
AB  - Ultrasound angiography (USAG), sonographic imaging of the blood flow with intra
      arterial infusion of carbon dioxide (CO2) microbubbles, was applied to pancreato
      biliary lesions. Hypervascular pattern was observed in all cases of gallbladder
      elevated lesions except for debris balls. However, the vascular pattern of CO2
      inflow that many arterial vessels were branching off into the lesion was
      characteristic for gallbladder carcinomas. The hemodynamics of solid tumors of
      the pancreas with USAG were divided into three patterns. Most of hypovascular
      nodules were duct cell carcinomas, while inflammatory pancreatic masses always
      exhibited isovascular except for two cases of hypovascular pattern. Furthermore,
      islet cell tumors showed hypervascular. In cases of mucin-producing cystic tumors
      of the pancreas, excrescent nodules or thickened septa within the lesions were
      identified as hypervascular. Other cystic tumors of the pancreas also presented
      peculiar hemodynamics. Therefore USAG is potentially useful for detecting various
      vascular patterns of pancreato-biliary lesions, contributory as a diagnostic tool
      in this area.

PMID- 9577624
TI  - [The usefulness of percutaneous ethanol injection therapy under guidance with
      carbon dioxide contrast enhanced ultrasound sonography].
AB  - We evaluated the usefulness of percutaneous ethanol injection therapy (PEIT)
      under Carbon dioxide (CO2) contrast enhanced ultrasound sonography (CEUS)
      guidance during digital subtraction angiography (DSA) in 21 cases of
      hepatocellular carcinoma (HCC) with 28 nodules that could not be detected by
      plain (non-contrast enhanced) US (PUS). In all cases of HCC that could not be
      visualized by PUS, PEIT could be performed successfully under CEUS guidance.
      Tumor size was below 10 mm in most cases, in 2 cases tumor size was more than 20
      mm. Tumor location was roughly divided into 5 areas: just below the diaphragm and
      it's vicinity, liver surface, edge of the liver, around the portal and hepatic
      vein, and around the inferior vena cave. The detection rate of the nodules that
      could not be visualized with PUS was 35.7% for CT and 32.1% for DSA. PEIT was
      performed 1-9 times for each lesion, 3.32 times on an average. The effectiveness
      of PEIT was judged by CT. All cases were confirmed as LDA. We concluded that the
      range of indication of PEIT can be expanded by this method.

PMID- 9577626
TI  - [Clinical assessment of contrast-enhanced ultrasonography for the diagnosis of
      gall bladder diseases].
AB  - We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) with intra
      arterial injection of CO2 microbubbles in 37 cases of gall bladder diseases. CEUS
      clearly visualized arterial flow and vascularity in every lesions without debris
      and gave us the precise information of vascular structure for the differential
      diagnosis of gall bladder tumors. For example, highly bifurcated tumor vessels
      and strong enhancement was observed in gall bladder cancer and we could detect
      relatively strong enhancement along the lumen with lack of enhancement of
      Rokitansky-Aschoff sinus in localized-type adenomyomatosis. Though CEUS is now an
      invasive modality, it will enable us to understand the non-invasive modality such
      as color doppler imaging with intra-venous administration of microbubbles in the
      future.

PMID- 9577627
TI  - [Color Doppler signal enhancement with SH/TH-508 in pancreatic tumors].
AB  - In this report, we showed the efficacy of a new contrast agent (SH/TA-508,
      Schering AG, Germany) for color Doppler imaging of the pancreatic tumors. In
      pancreatic ductal cancer, no enhancement of the lesion was observed, but vascular
      invasion by cancer became to be easily evaluated. On the other hand,
      hypervascular tumors such as islet cell tumor and cystadenocarcinoma, were
      increased in color Doppler signals of vessels by SH/TA-508. We concluded that
      SH/TA-508 was useful for evaluating the vascular invasion by pancreatic cancer as
      well as vascularity of hypervascular mass and solid component of cystic
      neoplasma.

PMID- 9577628
TI  - [Differential diagnosis of pancreatic tumor by contrast enhanced color Doppler
      ultrasonography].
AB  - For evaluating abdominal hemodynamic changes and diagnosing mass lesion, recently
      color Doppler ultrasonography (CDUS) have been applied. However, there are
      limitations in visualizing Doppler signals in small vessels with low flow
      velocity. To overcome these shortcomings, several contrast agents that facilitate
      evaluation of abdominal hemodynamics have been developed. We underwent Contrast
      enhanced color Doppler ultrasonography (CECD) with a galactose-based contrast
      agent in three patients with pancreatic tumor. In the patient with tumor forming
      pancreatitis, only CECD visualized the color signal in and around the tumor. In
      the patient with duct cell cancer, CDUS and CECD visualized only the color signal
      of the splenic artery penetrating the tumor, whereas in the patient with islet
      cell tumor, CECD visualized numerous color signals in the tumor. CECD appears to
      be useful in diagnosing pancreatic tumor.

PMID- 9577629
TI  - [Enhanced ultrasonography in the diagnosis of renal tumors].
AB  - At present, we have two methods of enhanced ultrasonography in the diagnosis of
      renal tumors. One is the ultrasound B-mode imaging enhancement under renal
      arterial infusion of carbon dioxide microbubbles, a contrast agent for US, and
      the other is the color Doppler signal enhancement under intra-venous injection of
      galactose-based echo contrast agent, SH/TA-508. Renal cell carcinoma were imaged
      from the very beginning of the injection of CO2 through the time complete washout
      from the kidney. On the other, intra-tumor color Doppler signals were remakedly
      emphasized after SH/TA-508 administration. Enhanced ultrasonography is useful in
      the detection of small renal cell carcinoma and differential diagnosis of renal
      masses.

PMID- 9577630
TI  - [Effect of ultrasound contrast medium in color Doppler of blood flow in
      transplant kidneys].
AB  - We have so far performed color Doppler echography to make diagnosis in renal
      transplantation. The ultrasound contrast agent in color Doppler developed and
      used recently has made possible the recording and measuring of low velocity wave
      in transplant kidneys. As characteristics of that, mention can be made of
      improvement in detection of the flow, reliability of assessment of the velocity,
      space resolving power. It is useful particularly for the peripheral blood vessels
      on chronic rejection and the interlobar artery on acute vascular rejection. With
      that put to practical use, imaging diagnosis in the field of renal
      transplantation has improved in its diagnosing ability and is expected to make
      further development in the future.

PMID- 9577631
TI  - [Color Doppler enhancement with contrast agents for the detection of prostatic
      cancer].
AB  - Transrectal color Doppler sonography for the prostate has been studied since
      1986. The detection rate of blood flow images inside the prostate were higher
      (89%, 49/55) in cases of prostatic cancer than in cases of other prostatic
      diseases (27 %, 12/45). These blood flow images were considered to be
      characteristic of prostatic cancer. Recently color Doppler enhancement with
      contrast agents were applied to transrectal sonography. In 9 cases of prostatic
      cancer, microbubble contrast agents (SH/TH508) were injected via an antecubital
      vein. Blood flow images were enhanced in all these cases. Even in cases of
      localized cancer, blood flow images were visualized clearly in the cancer lesion.
      This new modality might be useful for detection of prostatic cancer in early
      stages.

PMID- 9577632
TI  - [Contrast enhanced color Doppler imagings of testicular and penile lesions].

PMID- 9577633
TI  - [Contrast echo imaging on the breast and thyroid cancers].
AB  - The utility of ultrasound color Doppler flow mapping imaging for the differential
      diagnosis on the breast and thyroid tumors had already reported in 1991.
      Ultrasound contrast agent, SH/TA 508 (Levovist; Schering AG, Germany), had
      already finished clinical trials in Japan and reported the result phase II, III.
      On the breast and thyroid lesions, the utility of this contrast agent are safety
      and usefulness for the accurate diagnosis by the ultrasound color Doppler
      examination. Throughout of these clinical trials, a quit new ultrasound Doppler
      imaging methods had been developed, Harmonic Imaging and acoustic emission mode.
      As the result, ultrasound contrast agent is useful not only for the conventional
      color Doppler diagnosis but also for the developing of new diagnostic imaging
      methods.

PMID- 9577634
TI  - [Long-term clinical angiographic follow-up undergoing PTCA more than 10 years].
AB  - To evaluate longer-term outcome of the balloon angioplasty, a serial follow-up
      angiographic study at Early (< or = 1 year) and 10 year (yr)s was designed.
      Between April 1982 to December 1984, balloon angioplasty for native coronary
      arteries was successful in 320 patients (pts) (age: 60 +/- 9, male 81%, multi
      vessel disease 45%) or 436 de novo lesions (les) (LAD: 56%, RCA 20%, LCX 24%). At
      10 yrs, 78% of pts were free from death, 66% free from death/MI/CABG, 48% free
      from death/MI/CABG/target lesion revascularization. 41% free from
      death/MI/CABG/target lesion revascularization/PTCA for new les (NL). Early follow
      up angiography (FUA) was performed and cine films were available in 176 pts
      (55%). Seventy-three pts (23%) underwent target lesion revascularization and 11
      pts died (cardiac: 3, non-cardiac: 8) within 1 yr. Excluding these 84 pts, 236
      pts were eligible for longer term FU. FUA at 10 yrs was performed and cine films
      were available in 95 pts (40%). CAAS II was used for quantitative analysis.
      [table: see text] MLD did not change between Early and 10 yrs. Angiographic
      restenosis (defined as > 50% DS at FU) was occurred in 75/176 pts (43%) within 1
      year and 15/95 pts (16 %) between 1 and 10 yrs (P < 0.0001). In contrast, NL was
      occurred in 26/176 pts (15%) within 1 year and 45/95 pts (47%) between 1 and 10
      yrs (P < 0.0001). CONCLUSION: 1) Restenosis rarely occurred beyond 1 yr after
      balloon angioplasty. 2) Ischemic events beyond 1 yr were often related to
      development of NL rather than restenosis. 3) Safety and efficacy of balloon
      angioplasty appeared to be sustained at 10 yrs.

PMID- 9577635
TI  - [The molecular mechanisms of the instability of the CAG repeat].
AB  - Expansion of CAG trinucleotide repeats coding for polyglutamine stretches has
      been identified for seven neurodegenerative diseases including Machado-Joseph
      disease (MJD). There are many common features shared among these disease such as
      genetic anticipation i.e. accelerated age at onset in successive generations,
      which is also a result of intergenerational increase in the size of expanded CAG
      repeats. To identify elements affecting the intergenerational instability of the
      CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the
      CAG repeat in the MJD1 gene affects intergenerational instability. We suggested
      that an inter-allelic interaction is involved in the intergenerational
      instability of the CAG repeat and provide a clue to the molecular mechanisms of
      the instability of the CAG repeat.

PMID- 9577636
TI  - [Chromosome abnormalities and prognosis in childhood and adult leukemia].

PMID- 9577637
TI  - [Characteristics of childhood leukemia].

PMID- 9577638
TI  - [On psychology of patients and their families].

PMID- 9577639
TI  - [Chaos and the mechanism of genetic information maintenance in cancer].

PMID- 9577640
TI  - [Retrospective analysis of elderly patients > or = 60 years of age with acute
      leukemia].
AB  - A retrospective analysis was performed on 76 consecutive elderly patients with
      acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60
      69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were
      55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic
      leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were
      treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML,
      and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29
      of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations
      were 226, 85, 0 days, and the median survivals were 204, 177, 99 days,
      respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG
      regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained
      62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our
      results indicated that patients aged 60-69 years should be treated with intensive
      chemotherapy.

PMID- 9577641
TI  - [An analysis of sclerodermatous graft-versus-host-disease after allogeneic bone
      marrow transplantation: CD8+CD57+T-cell proliferation and increased production of
      TGF-beta].
AB  - A 19-year-old woman with acute lymphoblastic leukemia received an allogeneic bone
      marrow transplantation (BMT) from an HLA-identical sibling during the second
      remission, on September 28, 1993. The conditioning regimen consisted of total
      body irradiation and cyclophosphamide. Short term methotrexate and cyclosporin A
      were given for prophylaxis of graft-versus-host disease (GVHD). On day 771 after
      BMT, she complained of bilateral forearm pain, and developed sclerotic lesions on
      the skin of the abdominal wall, forearms and legs. The diagnosis of
      sclerodermatous GVHD was established by skin biopsy on day 834. The values of CRP
      and IgG were elevated, and both antinuclear antibody and anti-DNA antibody became
      positive. Flow cytometric analysis showed a significant increase in the number of
      CD57+ cells after appearance of sclerotic change. In addition, 65% of CD8+ cells
      were positive for CD57. Circulating level of transforming growth factor (TGF)
      beta 1 was high. These results suggest that overproduction of CD8+ CD57+ T cells
      and high level of circulating TGF-beta are related to the development of
      sclerodermatous GVHD.

PMID- 9577642
TI  - [Combination chemotherapy (CVP) in a patient with refractory idiopathic
      thrombocytopenic purpura (ITP)].
AB  - A 54-year-old woman, who had been given a diagnosis of idiopathic
      thrombocytopenic purpura (ITP) refractory to steroid therapy, was admitted to our
      hospital because of severe bleeding tendency. Splenectomy, high dose vitamin-C
      and interferon-alpha were not effective, although high-dose gamma-globulin had
      some effect. Since high-dose glucocorticoid was effective temporarily, we decided
      to perform chemotherapy. Seven courses of CVP chemotherapies (CVP; CPM 500 mg,
      VCR 2 mg, PSL 50 mg) prevented severe bleeding and did not have serious toxicity.
      Chemotherapy can be indicated for refractory ITP reactive to immunosuppressive
      therapy such as high-dose glucocorticoid.

PMID- 9577643
TI  - [Post-transplant EBV-associated lymphoproliferative disorders--report of two
      cases].
AB  - We report two cases of Epstein-Barr virus (EBV)-associated lymphoproliferative
      disorders (LPD) after allogenic bone marrow transplantation which were
      conditioned with regimens including antithymocyte globulin (ATG). The first case
      was a 31 year-old man which severe aplastic anemia who was transplanted from HLA
      matched unrelated donor conditioned with total lymphoid irradiation (TLI)/
      cyclophosphamide/ATG and prophylactic administration of ganciclovir Grade I acute
      GVHD improved in response to cyclosporine (CsA). LPD as a polyclonal
      epipharyngeal mass developed at day +53 and spontaneously regressed along with
      the withdrawal of CsA. Second case was a 11 year-old boy with acute
      myelomonocytic leukemia (FAB:M4E). He was transplanted from HLA B locus
      mismatched mother conditioned with total body irradiation (TBI)/busulfan/L
      PAM/ATG. He showed grade IV acute GVHD, which was controlled by steroids and FK
      506. LPD as a monoclonal intestinal lymphoma was diagnosed at day +82, and he was
      unsuccessfully treated with ganciclovir, acyclovir, chemotherapy and transfusions
      of EBV-specific cytotoxic lymphocytes in addition to discontinuation of
      immunosuppressants, and died at day +18 due to sepsis and multiple cerebral
      infarction. Early detection and introduction of appropriate treatment for post
      bone marrow transplantation LPD is necessary.

PMID- 9577644
TI  - [Localized pulmonary infiltration in chronic myelomonocytic leukemia].
AB  - A 38-year-old woman who had been treated for refractory anemia was admitted with
      severe pancytopenia, persistent fever and splenomegaly in May 1995. The bone
      marrow biopsy revealed hyperplastic marrow with marked fibrosis. Shortly after
      admission, cardiac tamponade developed. Though low-dose Ara-C therapy
      successfully controlled the tamponade, no hematological recovery was obtained.
      Then a chemotherapy consisted of Ara-C, acrarubicin and M-CSF was done and the
      neutropenia was improved. However, progressive leukocytosis with monocytosis and
      splenomegaly subsequently developed. Thus, the disease was considered to progress
      to CMML. Localized pulmonary infiltrates associated with a cavity, a pulmonary
      artery aneurysm and a recurrent high fever developed in October 1995. Though
      invasive pulmonary aspergillosis was suspected, blood and sputa culture, as well
      as serological tests were negative. In February 1996, massive hemoptysis occurred
      and the patient died due to respiratory failure after an emergency right
      lobectomy of the lung. Pathological examination of the operated lung disclosed
      that the localized pulmonary infiltrates consisted of monocytoid cells.
      Infiltration of the monocytoid cells in the tissue surrounding the pulmonary
      aneurysm was also observed. However, no pathologic organisms were detected at
      all. Thus, the leukemic cells were considered to have infiltrated locally into
      the lung.

PMID- 9577645
TI  - [Polyclonal plasmacytosis in peripheral blood and leukocytoclastic vasculitis in
      Castleman's disease].
AB  - A 62 year-old man had fever, splenomegaly, systemic lymphadenopathy and palpable
      petechiae. Laboratory studies showed leukocytosis (10,200/microliters) with
      plasma cells (23%) and polyclonal gammopathy. Southern blot analysis of
      peripheral blood mononuclear cells showed no rearrangement of immunoglobulin
      genes, indicating polyclonal plasmacytosis in peripheral blood. A diagnosis of
      Castleman's disease was made by the cervical lymph node biopsy, which showed
      onion-skin structures in the germinal centers and plasmacytosis in the
      interfollicular region. A skin biopsy of the purpura lesion disclosed
      leukocytoclastic vasculitis. This is an unusual case of Castleman's disease
      presenting plasmacytosis in peripheral blood and leukocytoclastic vasculitis.

PMID- 9577646
TI  - [Factitious anemia with severe iron deficiency caused by self-venesection].
AB  - A 22-year-old unmarried female student of nurse school was admitted to our
      hospital because of hypochromic anemia and fever of unknown origin. She was
      diagnosed as having iron-deficiency anemia and was treated with iron, but
      progressive anemia recurred periodically. In particular, rapidly progressive
      anemia was observed after the patient stayed overnight, so we strongly suspected
      factitious anemia. A search of her locker in the sickroom and her room at home
      revealed many syringes, injection needles and a bottle of blood. Factitious
      anemia was diagnosed and she confessed to self blood-drawing. After a psychiatric
      consultation, anemia tended to to resolve gradually. However she did not go to
      the hospital after 6 months from her discharge. Physicians should consider
      factitious anemia in a patient with severe chronic hypochromic anemia who dose
      not respond to adequate iron therapy, particularly in a patient with medical
      training.

PMID- 9577647
TI  - [Acute promyelocytic leukemia relapse as leukemia cutis shortly after complete
      remission with all-trans retinoic acid].
AB  - A 56-year-old man was admitted to our hospital in September, 1996. Chromosomal
      translocation (15; 17) and a PT-PCR study for PML-RAR alpha mRNA were positive in
      bone marrow aspirates, and acute promyelocytic leukemia was diagnosed. After CR
      was obtained with all-trans retinoic acid (ATRA) followed up with chemotherapy,
      the RT-PCR became negative. When he was readmitted in April, 1997, skin eruption
      on his chest and extremities were observed. Specimens taken for biopsy revealed
      leukemia cutis, and RT-PCR became positive in the same specimen. Bone marrow PT
      PCR was also positive without abnormal promyelocytes. Although he was treated
      with oral ATRA 80 mg/day again, no significant improvement in leukemia cutis was
      noted. After combined therapy with Ara-C and acularubicin, skin eruption
      disappeared and bone marrow RT-PCR became negative. A second CR was then
      obtained. Although it is unknown whether the administration of ATRA is related to
      extramedullary relapse or not, we recommend combined chemotherapy for such cases.

PMID- 9577648
TI  - [Neoplastic angioendotheliosis with Roth's spots].
AB  - A 81-year-old woman was admitted with fever, anemia and an elevation of serum LDH
      on September, 1995. She had anasarca and various abnormalities of the ocular
      fundus including Roth's spots. Skin eruption and psycho-neurological
      abnormalities were not seen. Laboratory data exhibited Hb 7.6g/dl, Plt 9.3 x
      10(4)/microliters, WBC 6,300/microliters and LDH 1932 IU/l. Antibiotics,
      antituberculotic drugs and steroids were not effective and she died on October,
      1995 with heart failure. An autopsy revealed that the small vessels of lungs,
      kidneys and the mucosa of the bladder and the gastrointestinal tract were filled
      with large mononuclear cells. Immunohistochemically these cells were positive in
      LCA and L26 stains, and negative in UCHL-1 stains. There fore this case was
      finally diagnosed as neoplastic angioendotheliosis (NAE). Although there has been
      no case report of NAE with Roth's spots previously, there is the possibility that
      Roth's spots appeared as a sign of vascular occlusion due to NAE. Roth's spots
      may be noteworthy as a sign of NAE that has few clinical features.

PMID- 9577649
TI  - [Serum iron in blood donors].
AB  - We accept blood donations from many people daily. It is important to clarify
      levels of serum iron (SI) in blood donors. We measured SI in 62,054 blood donors
      (37,989 male and 24,065 female) between 16 and 64 years of age. SI was 108.2 +/-
      39.5 micrograms/dl in males and 88.5 +/- 35.7 micrograms/dl in female. SI did not
      differ significantly with age in females, although it is slightly lower in women
      aged < or = 19 than in women aged < or = 20 years. In men, SI decreased with age
      from 20 to 64 years old, although the course of the decrease is not clear. These
      data should be of use to blood programme.

PMID- 9577650
TI  - [A report from neurological practice].
AB  - It was one of the great pleasures to have fulfilled my long-held dream in 1986,
      newly opened the Kitasato University East Hospital (KUEH). In 1965, I served at
      chronic ward of Baltimore City Hospitals as a resident of neurology, where most
      of the patients were relaxed and enjoyed their hospital life. Since then, my
      dream had been growing that chronic ward for neurological diseases was necessary
      in Japan, good for chronic cares as well as clinical research. KUEH include 89
      beds for neurological diseases, uniquely enough, of which 15 beds specially
      prepared for the patients with respiratory distress suffering from intractable
      neurological diseases. KUEH gave us a lot of medical informations, developed to
      clinical research. Some of them will be introduced briefly as follows; firstly,
      in three patients with Guillain-Barre syndrome (GBS) we found high titers of
      serum IgM and IgG antibodies associated with acute cytomegalovirus (CMV)
      infections. They also had high titers of IgM and IgG anti-GM2 antibodies. The
      titers of anti-GM2 antibodies decreased on absorption with CMV-infected cells.
      These new findings suggested that anti-GM2 antibodies are associated with acute
      CMV infections in GBS patients. Secondly, we have patients with autosomal
      dominant familial Parkinsonism in Sagamihara, Kanagawa. Their clinical features
      are not essentially different from solitary Parkinson disease, and they respond
      well to levodopa treatment. Three autopsied cases, however, revealed
      neuropathological findings much different from those of classical Parkinson
      disease, such as rather mild to moderate loss of melanin-containing cells, well
      maintained locus ceruleus neurons in number and no Lewy bodies detected at all.
      There are no reports in literatures of familial Parkinsonism from clinical and
      neuropathological points of view. Thirty-eight years have passed since
      establishment of the Japan Neurological Society, meanwhile the expertise
      neurologists come out. Neurology is, however, still minor in medical practice.
      This is my opinion that neurologist should take leadership in clinical medicine
      as well as in academic fields. We need tell people our work, how our neurologic
      expertise can help them treat various disorders such as stroke, pain, sleep, and
      headache, epilepsy as well as physical and mental rehabilitation for the
      establishment of our identity.

PMID- 9577651
TI  - [Immune mediated demyelinating polyneuropathies].

PMID- 9577652
TI  - [Molecular biological analysis of the development of the mammalian central
      nervous system].
AB  - Analysis of the neuropathological mutant animals offers us great information on
      the development and differentiation of the nervous system. I have here introduced
      two examples of the analyses of the various kinds of neuropathological mutant
      mice. First one is the mutant mice where Purkinje neurons in the cerebellum are
      absent. High molecular weight protein, P400, enriched in the Purikinje cells in
      the cerebellum was greatly decreased in the Purkinje cell deficient mutant mice,
      nervous, pcd, Lurcher. We demonstrated that P400 is equivalent to IP3 receptor
      type 1. We found that IP3 receptor type 1 plays an important role in Ca2+ wave in
      fertilization and long term depression in the cerebellum which is one of the
      typical example of neuronal plasticity in the cerebellum. Second mutant is reeler
      mice where neuronal positioning in the brain is abnormal. We found CR50 antigen,
      reelin is the key molecule as a secreted molecule from Cajal-Retzius neuron for
      the neuronal positioning. We produced IP3 receptor deficient mice by gene
      targeting. The birth rate was one fifth of the control and the animals die before
      25 postnatal days. They showed cerebellar ataxia and epileptic seizure.

PMID- 9577653
TI  - [Advances in the research on Alzheimer's disease--overview].
AB  - The number of patients suffering from dementia in Japan has been estimated to
      exceed 1,250,000 and is expected to increase rapidly in the near future. It is
      quickly becoming a serious medical and social issue. Alzheimer's disease (AD) is
      a leading cause of dementia, and can be classified into two genetic categories:
      single-gene and polygenic diseases. Familial Alzheimer's disease (FAD) is
      classified as a single-gene disease, while sporadic AD is classified as a
      polygenic disease which involves multiple genetic and environmental factors.
      Using positional cloning, most of the genes which lead to FAD have recently been
      identified e.g., the amyloid precursor protein (APP) gene on chromosome 21,
      presenilin I on chromosome 14 and presenilin II on chromosome 1. Recent studies
      indicate that mutations in these genes can result in either overproduction of A
      beta or in production of A beta 1-42. Although the accumulation of A beta has
      been suggested to be the "primary cause" not only in FAD but also in sporadic AD,
      it remains unclear how neurodegeneration in AD is related to the accumulation of
      A beta. The discovery of ApoE4 as a major genetic risk factor for AD has created
      a new step of research on AD as a polygenic disease. Although it is confirmed
      that the presence of the ApoE4 allele greatly accelerates age at onset of AD, the
      role of ApoE4 as a risk factor for AD remains to be fully elucidated. Now that
      major genes involved in the pathogenesis of AD have been identified, future
      research should be directed toward elucidation of the molecular mechanisms of how
      these gene products are involved in the pathogenesis of AD on protein as well as
      cellular levels.

PMID- 9577654
TI  - [Molecular genetics of Alzheimer's disease--presenilin and other genes].
AB  - We examined mutations of presenilin 1 (PS1), presenilin 2 (PS2) and amyloid
      precursor protein (APP) in 30 Japanese familial Alzheimer's disease (FAD) and 34
      isolated cases of Alzheimer's disease (AD). We found mutations of PS1 in 17% of
      early onset FAD (H163R, H163R, R269H, E273A, G384A) and in a case (H163R) of
      isolated AD. The remaining cases were free from mutations in PS1, PS2 and APP.
      Since only a part of them could he explained by ApoE epsilon 4, we concluded that
      important genes are missing. We also examined association of apolipoprotein E
      (ApoE)epsilon 4, allele A of alpha 1-antichymotrypsin (ACT), 5 repeat allele of
      very low density lipoprotein receptor (VLDLR) and Alzheimer's disease. We
      confirmed that ApoE espilon 4 is significantly more frequent in both FAD and
      isolated AD cases than controls. We could not see any significant association in
      the ACT polymorphism. The 5 repeat allele of VLDLR was slightly but significantly
      more frequent in AD cases than controls. However, association with ApoE epsilon 4
      was not seen in our study.

PMID- 9577655
TI  - [The AAP and PS1/2 mutations linked to early onset familial Alzheimer's disease
      increase the extracellular concentration and A beta 1-42 (43)].

PMID- 9577656
TI  - [beta-amyloidogenesis].
AB  - How and when does amyloid beta-protein accumulate in the brain? We sought to
      learn about when and how amyloid beta-protein (A beta) accumulates in the cortex
      of normal individuals and about the difference in the A beta accumulation between
      normal aged and Alzheimer's disease brains. From consecutive autopsy cases (n =
      76; age range: 24-92 years) and confirmed Alzheimer's disease cases (n = 7; age
      range: 60-79 years), hippocampus CA1 and occipitotemporal cortex T4 were sampled
      for A beta quantitation. The A beta 42 level increased steeply from age 50 to age
      70 years in T4 and a little later in CA1. It was consistently higher in T4 than
      those in CA1 in a given case. There was a critical level of A beta 42 below which
      no senile plaques were detected. In the Alzheimer's disease brains the A beta 42
      levels were significantly higher, and the extents of A beta 42 amino-terminal
      modifications were also much greater, than those in the control brains. In
      contrast to A beta 42, A beta 40 showed no age-dependent accumulation and its
      level was increased in most of the Alzheimer's disease brains. A beta 40 appears
      to invariably accumulate in the cortex during aging, and to a greater extent in
      Alzheimer's disease. Increased A beta 40 levels are associated with most
      Alzheimer's disease cases. An early onset of A beta 42 accumulation may lead to
      development of Alzheimer's disease late in life and increased levels of A beta 40
      may be involved in acceleration of development of the disease.

PMID- 9577657
TI  - [Peripheral nerve disorders--clinical pathological approaches].
AB  - Clinical pathological approach is defined as combination of neurological,
      neurophysiological and neuroradiological findings for the interpretation of the
      morphology of the sural nerve. For this purpose, first, the usefulness of
      simultaneous biopsy of sural nerve and ipsilateral short peroneal muscle was
      presented. This method has helped establish the diagnosis of angitis or
      amyloidosis in some cases. Furthermore, motor-dominant clinical picture was
      ascertained by relative preservation of sural nerve in contrast with severe
      changes in intramuscular nerve fascicles. Second, histochemistry using UEA-1
      lectin to detect somatic sensory C fibers was discussed. UEA-1 specifically binds
      to unmyelinated axons and small neurons in dorsal root ganglia as well as
      substantia gelatinosa of the spinal cord. Serial semithin and ultrathin sections
      were obtained. The semithin section was removed of epon and stained
      histochemically with UEA-1. Positive fibers in the semithin section was compared
      with the counterpart in the ultrathin sections. UEA-1 positive fibers were found
      to comprise 20% of all unmyelinated fibers and be randomly distributed among the
      entire nerve fascicles. The application of this technique to pathological
      specimens is now undergoing. Third, an autopsy case with sarin intoxication was
      reported as an example of systemic study of the peripheral nervous system. The
      patient was a 51-year-old man who inhaled sarin in the attack of Tokyo Subway. He
      fell into vegetative state and was passively maintained for 13 months. Peripheral
      sensory nerve showed typical pattern of dying back-type distal peripheral
      axonopathy. It might be indicated that peripheral nerve be carefully checked
      among the sarin victims. In conclusion, the aim of our approach is to combine all
      clinical information, introduce recent advance in neuroscience, and try to find
      possible cure to intractable neurological disorders.

PMID- 9577658
TI  - [Neurotransmitter-mediated regulatory mechanisms of axoplasmic transport-
      acetylcholine and adrenaline].
AB  - It has not been known whether or not the axoplasmic transport depends on
      regulatory influences mediated by neurotransmitters. The video-enhanced
      microscope technique has made it possible to visualize the real-time movement of
      micro-particles along axons and thus to observe its quick response to external
      signals. Using this technique, the effects of acetylcholine (ACh) and adrenaline
      on the axoplasmic transport in cultured cervical ganglion (SCG) cells were
      examined. Application of ACh inhibited the transport in both anterograde and
      retrograde directions. This effect was mimicked by the muscarinic receptor
      agonist arecoline, but not by the nicotinic receptor agonist nicotine. The
      response to ACh was inhibited by QNX (3-quinuclidinyl-xanthine-9-carboxylate), a
      muscarinic receptor antagonist. Immunocytochemistry and in situ hybridization
      with anti-muscarinic receptor subtypes compounds demonstrated the expression of
      m2 receptors on the SCG cell. Islet-activation protein (IAP), a G-protein
      inhibitor, completely blocked the suppressive effect of ACh. The protein kinase A
      (PKA) inhibitor KT-5720 induced a similar effect to that of ACh. In contrast to
      the effect of ACh, adrenaline increased both anterograde and retrograde
      transport. The beta 2-receptor agonist (albuterol), but not alpha-receptor
      agonists (phenylphrine and clonidine) or beta 1-receptor agonist (dobutamine),
      mimicked the effect of adrenaline. The beta 2-receptor antagonist butoxamine
      abolished the facilitatory response to adrenaline. Dibutyryl cyclic AMP, a
      membrane permeable cAMP, and forskolin, an activator of adenylyl cyclase, induced
      a similiar effect to that of adrenaline. These results suggest that 1) ACh,
      acting through m2-receptors, activates Gi-protein and thus inhibits cAMP
      synthesis, 2) adrenaline, acting through beta 2-receptors, increases
      intracellular cAMP concentration, and 3) these changes in cyclic AMP levels
      inhibit or enhance the activity of PKA to phosphorylate proteins related to the
      axoplasmic transport.

PMID- 9577659
TI  - [Neurotrophic factors and their receptor expressions in human neuropathies].
AB  - Currently, many neurotrophic factors are known to promote peripheral nerve
      regeneration after nerve injury or nerve degeneration. Among such neurotrophic
      factors, neurotrophin family (NGF, BDNF, NT-3, NT-4) and GDNF are most potent
      ones, and they have been demonstrated to express in the distal stump of the
      experimental nerve transection. In this study, we assessed the expression levels
      of neurotrophin mRNAs and GDNF mRNAs and their receptor mRNAs for p75, TrkA,
      TrkB, TrkC, GDNFR alpha and Ret in the sural nerve biopsy specimens from various
      human neuropathies. All the neurotrophin mRNAs and GDNF mRNAs were significantly
      elevated in the diseased nerves and their expression levels well correlated to
      the extent of T-cell and macrophage invasion. p75 and GDNFR alpha mRNAs were
      upregulated in correlation to the extent of axonal degeneration. On the other
      hand, the TrkB and TrkC mRNAs were likely downregulated. These findings suggest
      that the regulatory mechanism for expression of neurotrophins and GDNF mRNAs and
      their receptor mRNAs are different. Significant upreguration of the neurotrophic
      factor mRNAs in the nerve lesion would be the compensation mechanism reacting for
      the lesion, even in the lesions which are progressing in severity. Extrinsic
      supplement of these neurotrophins would be beneficial for promotion of repair of
      the peripheral nerve lesion particularly when they are progressive lesions.

PMID- 9577660
TI  - [Impairment of peripheral nerve excitability].
AB  - Functional abnormalities, especially the excitability changes of axon in the
      peripheral nerve involvement, were reviewed. In GBS and CIDP, the correlation
      between conduction block and anti-ganglioside antibodies have been discussed.
      Using anti GM1 antibody positive sera, the suppression of voltage-gated sodium
      channels (VGSC) has been reported. Although this findings have not been
      confirmed, the involvement of VGSC may be an important mechanism for eliciting
      conduction block. In Isaacs' syndrome, voltage-gated potassium channels (VGKC)
      were suppressed by autoantibodies to VGKC. Furthermore, in generalized myokymia
      syndrome which shows only myokymia and muscle cramp without grip myotonia, VGKCs
      are also suppressed in some cases. These findings suggest that some patients with
      myokymia and neuromyotonia are induced by anti-VGKC antibodies. For evaluating
      the axonal excitability in vivo, the threshold electrotonus method have been
      developed and applied for the involvement of peripheral nerves. In ALS,
      impairment of potassium conductance was shown and was speculated to have the
      possible rrelation with fasciculation. Thus threshold electrotonus method will be
      an important method for evaluating axonal excitability in human. The accumulated
      knowledge about the involvement of axonal ion channels will expand and will be
      categorized as axonal channelopathies.

PMID- 9577661
TI  - [Recent advances of immune therapies for demyelinating neuropathies].
AB  - Most of acquired demyelinating neuropathies are caused by immune-mediated
      processes. Therefore, we can treat these neuropathies to control underlying
      immune abnormality. We review the recent therapies and show possible strategies
      in the future. (1) Recent therapies Guillain-Barre syndrome should be treated
      quickly and intensively in the first week of the disease with plasmapheresis
      (PP). Intravenous immunoglobulin (IVIG) is as effective as PP. IVIG is under
      phase 3 clinical trial in Japan. Chronic inflammatory demyelinating
      polyneuropathy (CIDP) is treated with corticosteroids, PP or IVIG.
      Corticosteroids or PP is the first choice. For severe or resistant cases,
      combined therapy or immunosuppressants, such as cyclophosphamide pulse therapy,
      should be considered. Polyneuropathy with IgM-MGUS (monoclonal gammopathies of
      undetermined significance) is treated with PP, immunosuppressants or these
      combinations to decrease serum IgM, especially for cases with anti-MAG antibody,
      because the autoantibody induces demyelination by itself. (2) Future strategies
      Immunopathogenesis may differ among cases with Guillain-Barre syndrome or CIDP.
      The best therapy will be chosen individually, according to appropriate
      immunologic tests. In CIDP, immunomodulation therapies, that are similar ones in
      multiple sclerosis, will be considered to maintain improvement.

PMID- 9577662
TI  - [Movement and behavioral disorders in anterior cerebral artery territory
      infarction].
AB  - Anterior cerebral artery territory infarction, which affects the medial frontal
      lobe and anterior part of the corpus callosum, may cause disinhibitory movement
      and behavioral disorders. The pathophysiology of disinhibitory movement and
      behavioral disorders was discussed in relation to the role of the frontal lobe in
      motor control and hemispheric asymmetry of motor functions. Instinctive grasp
      reaction is the prototype of disjunctive motor disinhibition syndromes, and
      diagnostic dyspraxia and compulsive manipulation of tools are the most
      illustrative forms. Diagnostic dyspraxia can be defined as uncontrolled cross
      purposeful actions of the left hand triggered by voluntary activities of the left
      hand. In compulsive manipulation of tools, a patient, with the right hand, grasp
      and use tolls placed in front of them against the patient's will. The left hand
      often restrains the unintentional movement of the right hand in accordance with
      the patient's will. Utilization and imitation behaviors described by Lhermitte et
      al belong to disinhibitory behavioral disorders, in which volition of the patient
      or an individual as a whole is involved. External stimuli reflexively provoke the
      patient's will to act. The behaviors accordant with the will, even if
      inappropriate, are not compulsive, but the easily-raised volition in response to
      the stimuli is pathological. These disinhibitory disorders differ from
      disjunctive motor disinhibition syndromes because of lack of inconsistency
      between will and manifested behavior. Lesions in the frontal lobes has been
      suggested to be responsible for utilization and imitation behaviors.

PMID- 9577663
TI  - [Cerebrovascular disorder and the language areas].
AB  - Recent progress of imaging techniques has achieved precise descriptions of
      aphasic syndromes associated with cerebrovascular disorders. Infarction of the
      left anterior cerebral artery brings about transcortical motor aphasia. Occlusion
      of each branches of the left middle cerebral artery produces characteristic
      language symptoms. Recently, cases with infarction of the areas of prefrontal and
      precentral arteries were reported to manifest fluent aphasia indistinguishable
      from the classical transcortical sensory aphasia. Rare cases with lesions
      restricted to the Broca's area (territory of the precentral artery) produces
      aphasia with normal fluency, word finding difficulty and deficit in sentence
      comprehension. Classical non-fluent Broca's aphasia is caused by infarctions
      which at least involves the areas of precentral and central arteries. Aphemia or
      pure word dumbness results from damages which involves territory of the central
      artery. Conduction aphasia is most often associated with lesions of the posterior
      parietal artery territory. As in the case of Broca's aphasia, Wernicke's aphasia
      is a composite of conduction aphasia, pure word deafness, transcortical sensory
      aphasia, and alexia with agraphia. The lesion of Wernicke's aphasia naturally
      involves the areas of all of these aphasic symptoms. Transcortical sensory
      aphasia is associated with lesions in the posteroinferior temporal region, and is
      often associated with watershed infarctions of the middle and posterior cerebral
      arteries. Aphasia which results from putaminal hemorrhage has ambiguous
      manifestation, and is difficult to be classified into Wernicke-Lichtheim's model.
      Assessment of its fluency is notoriously difficult. Thalamic aphasia is similar
      to either anomic aphasia or transcortical sensory aphasia. It was pointed out
      that classical aphasic syndromes are still valid as cerebral arterial occlusion
      syndromes, but are insufficient for the purpose of more precise anatomo-clinical
      correlation.

PMID- 9577664
TI  - [Automatic-voluntary dissociation in apraxia].
AB  - Automatic-voluntary dissociation in apraxia was discussed and the following two
      points were noted 1) This phenomenon is observed for praxis with procedural
      memory, i.e., learned or skilled movements such as brushing teeth and dressing,
      but not observed for praxis without procedural memory such as tasks used for
      testing constructional apraxia. 2) This phenomenon may be understood by dual
      motor act systems, i.e. implicit and explicit motor systems. Presumably, the
      former is mainly mediated by medial premotor system that involitionally drives
      motor procedural memory, while the latter is mainly mediated dorsolateral
      premotor system that volitionally drives motor procedural memory.

PMID- 9577665
TI  - [Neuropsychological disorders in minor hemisphere damage].
AB  - Damage to the minor hemisphere or the right hemisphere of most right-handed
      subjects produces various neuropsychological disorders. Unilateral spatial
      neglect is the deficit to respond or orient to stimuli on the left side. The
      inferior parietal lobule is most frequently involved in the lesions of neglect
      patients, but lesions confined to the lobule may not cause chronic neglect.
      Severe and lasting neglect is frequently found in patients with an infarction in
      the territory of the middle cerebral artery or the anterior choroidal artery.
      Neglect is usually mild or moderate after frontal lesions. The most important
      mechanism of neglect seems to be disorders in spatial attention: rightward
      attentional bias, and impairment in disengagement and shift of attention from the
      right side. Directional hypokinesia is rarely observed in the chronic stage. Non
      spatial factors, such as motivational deficit, insufficient compensation with
      verbal intelligence, or disuse of an appropriate spatial strategy may also
      contribute to the appearance of neglect. Anosognosia for hemiplegia is found in
      about half of patients with acute cerebrovascular accidents in the right
      hemisphere. Generalized attentional and intellectual deficits, diffuse brain
      atrophy or hypometabolism, and presence of multiple infarction may result in
      chronic anosognosia. Constructional disability is observed in about 30% patients
      with either hemisphere damage. Dressing apraxia is more frequent in right
      hemisphere damage. These two disorders, however, rarely appear as isolated
      neuropsychological deficits. Most patients show some of the accompanying
      disorders, such as unilateral spatial neglect, anosognosia, anosodiaphoria, and
      generalized attentional and intellectual impairment. By contrast, motor neglect
      may occur independently of the other disorders. Motor neglect follows damage to
      either hemisphere, although it occurs more frequently after right hemisphere
      damage. Neuropsychological deficits characteristic of right hemisphere damage may
      be unilateral spatial neglect in the acute and chronic stages and anosognosia for
      hemiplegia in the acute stage.

PMID- 9577666
TI  - [Visual agnosia induced by cerebrovascular disease].
AB  - Visual objects can be classified into some categories such as faces, landscapes,
      objects and letters. Visual agnosia specific to one of these categories can
      occur. This type of visual agnosia occurs at the occipitotemporal lobe lesion
      where the visual cognitive center exists, and is often induced by vascular
      disease of the posterior cerebral artery. In this study we categorized the
      symptoms of visual agnosia and presented the natures of these symptoms of
      patients, and then investigated the lesions responsible for the symptoms. In
      addition, we clarified the current most important issue for each symptom. Based
      on our results, we discussed the visual cognitive functions of the
      occipitotemporal lobe. The results indicate that visual cognitive dysfunction
      with respect to faces, landscapes, objects and letters corresponds to
      prosopagnosia, agnosia for streets, associative object agnosia and pure alexia,
      respectively. Investigation of the relationship between the symptoms of the above
      conditions and the responsible regions shows that the right medial-posterior
      region, right medial-anterior region, both lateral regions (left side is
      superior) and the left medial region are important in the visual cognition of
      faces, landscapes, objects and letters, respectively. Thus, it is speculated that
      the visual cognitive functions occur independently at different regions of the
      occipitotemporal lobe for each visual category.

PMID- 9577667
TI  - [Progressive supranuclear palsy].
AB  - Progressive supranuclear paly (PSP) was firstly reported by Steel in 1964. This
      condition was separated from Parkinsonism by both clinical symptoms and
      neuropathological findings. Recently, in an attempt to improve diagnostic
      accuracy to give appropriate informed concepts and to select correct cases for
      drug studies or other research purpose, diagnostic criteria for PSP have been
      developed. PSP begins in the presenile period and duration of illness is 5.9
      years (1.2-10.3 years; Maher and Lees, 1986). Cardinal clinical symptoms of PSP
      are supranuclear gaze palsy, neck dystonia, parkinsonism, pseudobulbar palsy,
      gait imbalance with frequent falls and subcortical dementia. Supranuclear gaze
      palsy and bradykinesia are essential for diagnosis. MR-imaging of PSP shows
      dilatation of the third ventricle. Other laboratory examinations show no specific
      findings. Neuropathologically, marked dilation of the third ventricle and volume
      loss of periaqueductal area of the midbrain are noted in macroscopic view.
      Microscopical examination reveals neuronal loss and gliosis in the tegmentum, the
      tectum, periaqueductal gray, the dentate-rubro-pallido-luysial area, and the
      inferior olivary nucleus. Neuropathological hallmarks of PSP are neuronal loss,
      presence of the globose typed neurofibrillary degeneration, and glial tangles (so
      called tuft shaped astrocyte and coiled body). Atypical cases of PSP are
      reported. Such cases are reported as pure akinesia, PSP without ophthalmoplegia,
      dementia predominant PSP, pathologically diagnosed pallido-nigro-luysial atrophy
      (PNLA), pathologically diagnosed corticobasal degeneration which showed no
      laterality, and so on. Reported cases as pure akinesia was diagnosed as PSP or
      PNLA by neuropathological findings. Improvement of diagnostic accuracy in PSP is
      expected to ithrapeutic trials, to investigate the etiology, and to separate the
      other clinical entity from PSP.

PMID- 9577668
TI  - [Corticobasal degeneration].
AB  - Corticobasal degeneration (CBD) was first reported by Rebeiz et al as
      corticodentatonigral degeneration with neuronal achromasia in 1967. After Gibb et
      al described 7 cases including 4 cases from the literature under the term of
      corticobasal degeneration, CBD has become widely recognized. The disease starts
      mainly in one's fifties and sixties with the duration of 6 to 7 years. The
      clinical features include asymmetric parkinsonism, cerebral cortical signs, and
      others. Typically, patients present with unilateral clumsiness with akinetic
      rigid syndrome and limb-kinetic apraxia. Postural instability, gait disturbance
      and involuntary movements such as dystonia are not uncommon. The parkinsonism is
      DOPA-resistant. BEsides apraxia, alien limb syndrome, cortical sensory
      disturbances, frontal lobe-release signs, and dementia are representative
      cortical signs. Other clinical features include dysarthria, pyramidal tract signs
      and supranuclear gaze palsy. MRI, SPECT or PET reveals asymmetric atrophy,
      decrease in blood flow or reduction in metabolism of the frontal parietal region
      around the central sulcus. Electrophysiological and magnetic stimulation studies
      demonstrated increase in excitability of the cerebral cortex. Myoclonus in CBD is
      cortical in origin but without any preceding potential or giant somatosensory
      evoked potential. Neuropathologically CBD is characterized by involvement of the
      particular cortices and substantia nigra. Other structures such as the putamen,
      pallidum, thalamus, subthalamus, cerebellar dentate nucleus and brainstem are
      affected to various extents. Histological features include achromatic, ballooned
      neurons as well as tau and Gallyas positive neuronal and glial intracytoplasmic
      inclusions. Astrocytic plaque is considered to be a form of glial inclusions
      specific to CBD. Diagnosis of typical cases of CBD appears easy but atypical
      cases were reported with showed dementia or aphasia as a main feature, or were
      devoid of the asymmetry of signs and symptoms. CBD, progressive supranuclear
      palsy and Pick's disease share both clinical and neuropathological features to
      some extent while they are clearly distinct among typical cases. The etiology and
      pathomechanism of CBD remain to be elucidated.

PMID- 9577669
TI  - [Diffuse Lewy body disease].
AB  - Lewy body disease (LBD) is a progressive neurological disorder with parkinsonism,
      having many Lewy bodies (LBs) and degenerative changes. LBD is classified into
      the three types according to the distribution of LBs: "brain-stem type",
      "transitional type" and "diffuse type". The brain-stem type is identical to
      classical Parkinson's disease (PD). The diffuse type is nominated as "diffuse
      Lewy body disease" (DLBD). DLBD is a neuropathological entity, characterized by
      abundant LBs not only in the basal ganglia and brain-stem but in the cerebral
      cortex, combined with senile changes. Juvenile onset DLBD is called "pure form"
      of DLBD because of no or few senile changes. The LBs are present in the amygdala,
      nucleus basalis of Meynert, hypothalamic nuclei, substantia nigra, nucleus
      paranigralis, locus caeruleus, dorsal vagal nucleus and reticular nuclei. The
      cerebral LBs are numerous in the parahippocampal gyrus, cingular gyrus, and
      insular, frontal and temporal cortices. The LBs show immunoreactivity to
      ubiquitin and the ubiquitin-immunoreactive neurites in the CA2-3 region appear to
      be specific for DLBD. The clinical features of DLBD in the senium are progressive
      dementia, psychotic state, parkinsonism and autonomic signs. In general,
      progressive dementia is an initial symptom, followed by parkinsonism in the later
      stage. Some show progressive autonomic failure. A few present respiratory failure
      or vocal cord palsy resulting in sudden death in DLBD. DLBD is characterized
      neurochemically by severe affection of multiple neurotransmitters networks. In
      DLBD an impairment of the innominato-cortical cholinergic and mesocortical
      dopaminergic system, differentiating from Alzheimer's disease and PD, may play an
      important role in developing disease process.

PMID- 9577670
TI  - [Segawa disease].
AB  - Segawa disease (hereditary progressive dystonia with marked diurnal fluctuation)
      is an autosomal dominant, childhood onset, postural dystonia and the first
      hereditary basal ganglia disorder whose causative enzyme and gene defect were
      clarified. The initial symptom is unilateral pes equinovarus with marked diurnal
      fluctuation. Progression becomes slower after mid-teens and stationary after
      thirties. Postural tremor may occur after 10 years of age, especially after
      thirties. Parkinsonian resting tremor action and torsion dystonia. and disturbed
      locomotion do not occur. L-Dopa shows marked and sustained effect without side
      effects. F-Dopa PET and [11C] raclopride PET of over 20-year-old cases are
      normal. Deficiency of GTP cyclohydrolase I (GCH-I) was suggested from low CSF
      biopterin and neopterin. Mutation of GCH-I gene and decreased GCH-I were
      clarified as etiology. Twenty-five mutations discordant among families have been
      found. Autopsy of a gene proven case revealed decreased striatal tyrosine
      hydroxylase (TH) and dopamine (DA) in ventral striatum where direct pathway is
      predominant. Decreased GCH-I causes decreased tetrahydrobiopterin (BH4), TH and
      DA in nigrostriatal (NS) terminal. The lowest affinity of BH4 to TH causes
      selective involvement of DA. Postural dystonia is caused by decreased TH and DA
      affecting D1-direct pathway. Thalamic ventrolateral and pedunculo-pontine nuclei
      are spared. Diurnal fluctuation of symptoms is due to diurnal fluctuation of TH
      and DA at NS-DA terminal. Decreased DA to below 20% of normal, shown by
      polysomnographical studies, and its physiological age related decremental changes
      in NS-DA terminal underlies characteristic clinical course. High D2 receptor
      before early thirties masks D1 related hypertonus and manifest progression before
      20 years of age. Other pteridine abnormalities also cause dopa responsive
      postural dystonia with diurnal fluctuation. A case of juvenile parkinsonism
      without dystonia showed decreased TH in dorsolateral putamen where indirect
      pathway is predominant. These suggest that decreased TH due to decreased BH4
      involves D1-direct pathway causing dystonia, and decreased TH itself involves D2
      indirect pathway causing parkinsonism.

PMID- 9577671
TI  - [Huntington disease].
AB  - The gene responsible for Huntington's disease produces a protein with a molecular
      weight of about 350k, designated huntingtin. We identified both wild-type and
      mutant huntingtin in the brain and lymphoblastoid cells. Although the function of
      huntingtin is still unknown, several associated proteins such as HAP1, Ubiquitin
      conjugating enzyme, HIP1 and glyceraldehyde-3-phosphate-dehy dorogenase (GAPDH)
      were reported. We found the huntingtin can associate in vitro with microtubules.
      Through the process of assembly and disassembly of microtubules, both wild-type
      and mutant huntingtin associate with microtubules to almost the same degree. The
      results suggest that huntingtin may have a role in intracellular organelle
      transport or axonal transport by its association with microtubules. The
      functional disturbance by expanded polyglutamine stretch may modify the feature
      of the disease.

PMID- 9577672
TI  - [Postgraduate and continuing educations of neurology--comparison between Japan
      and foreign countries].

PMID- 9577673
TI  - [Can we treat amyotrophic lateral sclerosis?].

PMID- 9577674
TI  - [Instability of myotonic dystrophy CTG trinucleotide repeat].

PMID- 9577675
TI  - [Magnetic stimulation in amyotrophic lateral sclerosis].

PMID- 9577676
TI  - [Diabetic neuropathy: pathogenesis and treatment].

PMID- 9577677
TI  - [Functionality and connectivity analysis by magnetic resonance imaging].
AB  - Magnetic resonance (MR is a remarkably versatile technology applicable to various
      aspects of medical science. Currently, there are three categories of MR
      techniques available for probing human brain function in detail. The first
      category comprises the most widely utilized techniques which make use of the
      metabolic effects of brain activation, represented by BOLD (blood oxygenation
      level dependent) functional magnetic resonance imaging (fMRI). The second
      category of techniques deals with apparent diffusion tensor probing the axonal
      connectivity and is represented by three dimensional anisotropy contrast (3DAC)
      axonography. The third category of techniques is a biological application of
      classical nuclear magnetic resonance (NMR) spectroscopy capable of providing
      biochemical information in vivo and is represented by spectroscopic imaging (SI).
      As techniques directly applicable to clinical medicine, BOLD fMRI and 3DAC
      axonography possess the highest potential.

PMID- 9577678
TI  - [Hemispatial neglect: symptomatology, lesion localization and underlying
      mechanisms].

PMID- 9577679
TI  - The effect of ethanol upon early development in mice and rats. XXIV. The effect
      of acute ethanol intoxication upon implantation in mice.
AB  - The effect of acute ethanol intoxication (ethanol 33%, i.v.) on day 4 of
      pregnancy (at 9 o'clock a.m.) upon the initial stages of implantation in mice was
      investigated. The pregnant animals (treated and controls) were killed in the
      afternoon and in the evening of day 5 of pregnancy (at 30 and 36 hours after
      ethanol administration). After histological proceeding, the pregnant uteri were
      microscopically examined, using the following criteria: the position of embryos,
      the stage of embryos differentiation, the aspect of uterine epithelium, the
      decidual reaction and the presence of oedema. The results obtained are analysed
      and compared with some literature data and with our previous results. Some
      apparent contradictions between the data presented and those previously reported,
      require new investigations.

PMID- 9577680
TI  - [Appearance of dentine in scanning electron microscopy].

PMID- 9577682
TI  - Morphometric investigations on bone giant cell tumors.
AB  - The authors have studied 12 cases of bone giant cell tumors and have shown that
      the increase in aggressiveness is accompanied by higher values of mitotic
      activity and nuclear features (area, perimeter, long and short axes), which might
      be useful for grading the bone giant cell tumors.

PMID- 9577681
TI  - Morphophysiopathologic studies on the biology of myocardium in acquired
      valvulopathies.
AB  - Myocardial lesions due to various valvulopathies were sampled during open heart
      surgery under extracorporeal circulation, and histologically,
      histoenzymologically and ultrastructurally investigated. Various cardiomyocitary
      and interstitial nonspecific progressive lesions, due especially to hemodynamic
      and hypoxic alterations, were identified. During the pathogenic stages, we
      remarked the onset and chronic evolution of perivascular and interstitial oedema,
      enhanced by a reduced lymph draining. The progressive processes of hyalinization,
      sclerosis and interstitial fibrosis were subsequent to the interstitial matrix
      modification. These processes accentuate the myocardial hypoxic lesion due to the
      nutritional and gaseous exchange alterations. The infrastructure, mitochondrial
      enzyme equipment, sarcoplasma and tubular network lesions, as well as the
      intramyocitary oedema that destroys the sarcomeric structure, ended with the
      activation of lysosome and lysosomal enzymes, giving rise to consequent cytolytic
      foci. Therefore, the process was extending. In this context, we remarked at the
      electronmicroscopic examination ventricular natriuremic granules, that are rarely
      mentioned in literature.

PMID- 9577683
TI  - Immunohistochemical identification of ito-cells with smooth muscle cell anti
      actin in normal and pathological liver.
AB  - Eighteen patients with chronic hepatitis of viral and alcoholic etiology
      investigated and core needle biopsy of the liver was performed. Microscopical
      investigation consisted of pathological diagnosis, grading and staging of chronic
      hepatitis and identification of ito cells with smooth muscle cell anti-actin. Ito
      cells were noted mainly around portal spaces as small cells with vacuolated
      cytoplasm. Their number is higher in normal liver and chronic persistent
      hepatitis. Few ito cells were observed in active forms and they are absent in
      almost all cases with cirrhosis. In chronic hepatitis of alcoholic origin, ito
      cells are large and their cytoplasma contains many vacuoles. A strong correlation
      between the number of ito cells and the stage of the chronic hepatitis was noted
      but it was not possible to correlate the same parameter with Knodell score.

PMID- 9577684
TI  - Pseudoepithelimatous hyperplasia positive and differential diagnosis.
AB  - Our study intended to describe some inflammatory and tumoral lesions associated
      to pseudoepithelimatous hyperplasia. In our casuistry, pseudoepithelimatous
      hyperplasia was determined by tuberculosis in two cases, granulomatous ulcerate
      epuils in 4 cases, myoblastoma in one case. Recognising these lesions is very
      important, since it helps differentiating between these tumors and some epidermal
      carcinomas, the two affections involving different therapies.

PMID- 9577685
TI  - Remarks on some cases of stromal hyperplasia and endometrial sarcoma.
AB  - Our study works out different aspects which can appear both in stomal
      hyperplasias and endometrial sarcoma. It is possible to recognise histopathologic
      varieties of the stromal hyperplasias by a close co-operation with the
      gynaecologist. The necessity of a right diagnosis for all the forms of stromal
      hyperplasia spreads from the significance of precancerous lesion of some of them.
      We also mention the difficulties of diagnosis risen by stromal hyperplasias and
      endometrial sarcoma and also the necessity of a certain diagnosis having into
      consideration the prognostic and the different therapy imposed by the two
      diseases.

PMID- 9577686
TI  - Retroperitoneal extraadrenal paraganglioma report of two cases.
AB  - Two cases with retroperitoneal tumours affecting young women who cannot undergo
      surgery were investigated by biopsy and needle sampling. One of these cases
      presented a mainly alveolar histologic pattern and was easily diagnosed by
      immunohistochemical means, as well as a chromaffin paraganglioma. We discussed
      different diagnoses and approaches in the literature.

PMID- 9577687
TI  - Carcinosarcoma (malignant mesodermal mixed tumor) or urinary bladder.
AB  - The authors report a case of carcinosarcoma (malignant mesodermal mixed tumor of
      the urinary bladder. We discuss the histological criteria of positive and
      differential diagnosis, the histogenesis, as well as their biological behavior.

PMID- 9577688
TI  - Making change.

PMID- 9577689
TI  - Cervical neoplasia. History-screening-diagnosis-treatment.
AB  - Health care providers are exposed early in their education to the pathological
      classifications of cervical neoplasia. The significance of this early education
      may at first be hard for some to grasp. However, as one delves more deeply into
      the history of cervical cancer, the natural progression of early lesions, and the
      tremendous advances made in the diagnosis and treatment of cervical cancer in the
      past fifty years, the importance of this early education is very apparent. With
      the widespread use of The Bethesda System of lesion classification, the
      introduction of the ThinPrep pap smear and HPV DNA typing, and ever evolving
      therapeutic techniques, it seems timely to review the history, screening,
      diagnosis, and treatment of cervical neoplasia.

PMID- 9577690
TI  - Chronotherapeutics: is timing everything?

PMID- 9577691
TI  - Managed care and the enterococcus.

PMID- 9577692
TI  - Guidelines for the prevention and control of vancomycin resistant enterococci
      (VRE) in long-term care facilities. Sioux Falls Task Force on Antimicrobial
      Resistance.

PMID- 9577693
TI  - [On the 75th anniversary of the founding of the journal Urologiia].

PMID- 9577694
TI  - [The role of dynamic observation in the prevention of recurrences of stone
      formation].
AB  - 26 patients with recurrent and non-recurrent urolithiasis treated surgically or
      by lithotripsy and 14 patients free of urolithiasis were examined biochemically
      by 9 metabolic blood and urine parameters and using Litos test proposed by
      urologists of the Moscow Regional Research Clinical Institute for detecting
      lithogenesis in the kidneys. The comparison of the findings obtained with
      biochemical and Litos tests showed that these tests are mutually complementary.
      Monitoring of urolithiasis patients should be complex, i.e. including biochemical
      examination for disbolism and urinalysis by means of Litos test.

PMID- 9577696
TI  - [The phenomenon of the pathological crystallization of stone-forming urinary
      salts in urolithiasis].
AB  - It is known that when drying a drop of biological liquid under the action of
      osmotic forces acquires certain structure. The salts, which possess stronger
      osmotic potential, undergo crystallization in the center of the drop while
      protein components form the peripheral amorphic zone. In urolithiasis this
      process is impaired and crystallization of lithogenic salts occurs in the protein
      zone of a urine drop. This phenomenon discovered by the authors is designated as
      phenomenon of pathological crystallization of urine lithogenic salts. In
      nephrology and urology the above phenomenon may find application in diagnosis and
      control of urolithiasis activity, assessment of efficacy of the treatment
      conducted.

PMID- 9577695
TI  - [Lipid peroxidation and the antioxidant system of patients with urolithiasis
      after extracorporeal lithotripsy].
AB  - Activity of superoxide dismutase (SOD) in red cell membranes, levels of malonic
      dialdehyde (MDA) and dienic conjugates (DC) in blood plasma, red cells and urine
      were studied in 53 nephrolithiasis patients. A session of extracorporeal shock
      wave lithotripsy stimulated lipid peroxidation (LPO) in renal parenchyma
      manifesting with increased DC excretion with urine (an 89% increase). In red cell
      membranes SOD activity fell by 18%, DMA concentration rose by 16%. A two-week
      intake of vitamin E in a dose 100 mg/day elevated plasma alpha-tocopherol,
      diminished plasma MDA by 55% and prevented LPO activation in red cell membranes
      and renal parenchyma.

PMID- 9577697
TI  - [The effect of freezing the kidney in the terminal stage of hydronephrosis on its
      parenchymal function, arterial pressure regulation and erythropoiesis].
AB  - The authors studied morphological changes in renal tissue in terminal
      hydronephrosis and in exposure of freezing, regulation of arterial pressure and
      erythropoiesis in cryogenic effects on hydronephrotic kidney in experiment.
      Reparative changes in the parenchyma appear on day 30 after freezing, systemic
      arterial pressure and bone marrow erythropoietic activity returned to normal.
      Freezing is thought more physiological compared to nephrectomy in respect to
      prevention of nephrogenic hypertension and anemia.

PMID- 9577698
TI  - [The dependence of the progression of chronic glomerulonephritis on the clinical
      and morphological types of glomerulonephritis and on the tubulointerstitial
      changes].
AB  - Progression of chronic glomerulonephritis (CGN) is strongly associated with
      morphologic type of the disease, tubulointerstitial changes, some clinical
      syndromes. The aim of the study was to trace relations between the onset of
      chronic renal failure within 7 years since the diagnosis (fast progression of CGN
      -FP CGN), CGN clinical variant according to M. Ia. Ratner et al. classification
      (1987) and histomorphological changes in the renal biopsy. Unfavorable clinical
      types (active nephritic types and nephrotic-hypertensive type) proved dominating
      predictor of FP CGN not only because of close relationship between these type and
      FP CGN but also due to FP CGN occurrence in morphologically unfavorable
      morphological types and tubulointerstitial changes in line with concomitant
      unfavorable clinical types.

PMID- 9577699
TI  - [Plastic repair of the bladder using the intestine].

PMID- 9577700
TI  - [Validation of the treatment of the neurogenic bladder in children with
      myelodysplasia using pikamilon].
AB  - An original Russian drug pikamilone with central (vegetotropic, vascular) and
      peripheral (vasodilation) mechanism of action and m-cholinolytic atropine were
      investigated for effect on detrusor function in the accumulation phase in 26
      children with neurogenic bladder due to myelodysplasia. The detrusor function was
      assessed at retrograde cystometry performed before and after the drugs
      administration. The cystotonograms were estimated using a computer program of
      Relief urosystem according to the standard and additional indices. Pikamilone was
      found to potentiate the effects of atropine. This may be due to improvement of
      circulation and reduction of detrusor hypoxia. It is stated that selective
      chemotherapy of neurogenic bladder is uneffective. The preference should be given
      to combination of the drugs affecting main components of its dysfunction
      pathogenesis. Pikamilone should be referred to basic drugs for treatment of
      neurogenic bladder in spinal patients as its combination with atropine possesses
      a unique efficacy in restoration of the reservoir function of the bladder.

PMID- 9577701
TI  - [An analysis of preliminary results in screening for prostatic cancer].
AB  - 450 males aged over 50 years free of urological symptoms were screened for
      prostatic cancer using three techniques; finger rectal examination (FRE),
      transrectal ultrasound investigation (TUI), assay for prostatic specific antigen
      in the serum (SPSA). SPSA quantities under 4 ng/ml, 4-10 ng/ml, 10-20 ng/ml, over
      20 ng/ml were registered in 206(45.8%), 135(30%), 69(15.4%) and 40(8.8%)
      patients, respectively. Detectability of prostatic cancer increases by 33,37.9,
      45.5, 69.2% due to TUI, FRE, TUI + FRE, all the three methods, respectively.
      Prostatic biopsy was needed in 102 (22.7%) cases. From the 450 examinees,
      prostatic cancer was diagnosed in 25 (5.6%). SPSA was high in all of them, higher
      than 10 ng/ml in 92%. 20 (80%) of 25 patients with cancer had early stages of the
      disease (TI-2). The study is going on.

PMID- 9577702
TI  - [Hemorrhagic complications after an operation for adenomectomy].
AB  - The authors observed 49 patients aged 65-83 years with benign prostatic
      hyperplasia (BPH) before and after adenomectomy. It was found that prognosis of
      hemorrhagic complications of adenomectomy in early and late postoperative period
      demands a comprehensive assessment of coagulation and anticoagulation systems
      (fibrinolytic activity, first of all), ultrasound investigation (size of BPH),
      blood count and urinalysis (absence of residual inflammation of the urinary
      tract). Postoperative severe hemorrhage was observed in patients with changes in
      several parameters. It also was related to size of BPH and preoperative
      fibrinolytic activity. Early postoperative hemorrhages were more frequent than
      late (34.6% against 10%, respectively). 17 patients had micro- or macrohematuria,
      2 patients developed massive blood loss. All the hemorrhagic patients had
      preoperative hemostasis disorders manifesting primarily as enhanced fibrinolytic
      activity and reduced fibrinogen concentrations.

PMID- 9577703
TI  - [The efficacy of alfuzosin (dalfaz) in patients with benign prostatic
      hyperplasia].
AB  - A daily dose of alfusosine (an uroselective blocker alpha-l-adrenoreceptors
      produced as dalfas by Synthelabo Group, France) was given for 12 weeks to 124
      patients with benign prostatic hyperplasia. The patients were examined before the
      treatment and on the treatment week 4, 8 and 12. The response (improved quality
      of life, higher rate of urine flow, smaller amount of residual urine in the
      bladder) was achieved in 120 (96%) patients. Alfusosine effect was more
      pronounced in patients with severe defects of urination. The drug was well
      tolerated, side effects observed in 7(5.6%) patients were mild and did not
      require treatment discontinuation. Alfusosine is indicated in benign prostatic
      hyperplasia with moderate infravesical obstruction, significantly disturbed
      urination caused by hypertonicity of bladder cervix smooth muscles, posterior
      urethra and prostate.

PMID- 9577704
TI  - [Electromyography of the penis in the diagnosis of erectile dysfunction after
      radical operations on the organs of the lesser pelvis].
AB  - The paper presents the technique and results of electromyography of the penis
      (EMP) for 68 males divided into 3 groups: 21 volunteers with erectile disorders,
      20 patients with nonvasculogenic erectile dysfunction and no history of pelvic
      operations, 27 patients with erectile abnormalities as a result of pelvic
      operations (after cystectomy -11, cystoprostatectomy -1, rectal resection -7,
      rectal extirpation -8 patients, groups 1, 2, 3 and 4, respectively). Autonomic
      innervation of the penis is primarily characterized by such EMP parameters as
      amplitude, synchronism and frequency of potentials. Neurogenic penile disorder
      was identified in 3 patients of group 2 (1 patient with intervertebral disk
      hernia, 2 patients with lumbosacral osteochondrosis), in all patients of group 3
      (electric silence was recorded in 22 patients). EMP should be included in the
      algorithm of examination of patients with erectile dysfunction as providing a
      reliable assessment of autonomic penile innervation.

PMID- 9577705
TI  - [Changes in the enzyme level of the sperm of men with infertility].
AB  - Spermatic enzymes (fructose, alkaline phosphatase, gammaglutamyl transferase,
      alpha-glucosidase, dipeptydil aminopeptidase IV) were measured in 200 patients
      with secretory-toxic infertility. It is shown that in some variants of
      infertility changes in the levels of spermatic enzymes are compensatory. These
      changes may also reflect qualitative characteristics of spermatozoa.

PMID- 9577706
TI  - [The role of persisting microflora in the development of pathospermia].
AB  - The paper presents the results of the study of species composition and biological
      signs of microflora of the ejaculate obtained from infertile males. The strains
      of the microorganisms were characterized by high adhesive capacity and multiple
      resistance to antibiotics. High antilysozyme activity in staphylococci and
      enterobacteria isolated from the sterile patients was registered. The correlation
      between spermatozoa motility, lysozyme level in the ejaculate and bacterial
      ability to inactivate lysozyme is demonstrated the hypothesis about the role of
      persistent properties of bacteria in pathogenesis of male infertility is
      discussed.

PMID- 9577707
TI  - [The protein spectrum of ejaculates with different fertilities].
AB  - Immunochemical assay for protein composition was made in 22 fertile and 110
      subfertile human sperm samples. Changes in the levels of albumin, prostatic acid
      phosphatase, sperm-specific tripsin inhibitor, prostate-specific antigen and
      alpha-2-microglobulin of fertility in spermoplasm were studied in different
      disturbances of ejaculate fecundating ability. The latter was determined by 14
      morphofunctional and physicochemical criteria of sperm fertility. With an
      increase of the ejaculate volume above 5 ml protein homeostasis showed
      abnormality. The authors consider functional value of the study proteins in
      ejaculate, pattern of spermatozoid motor activity, maintenance of normal
      spermoplasmic pH; discuss practical opportunities of the data obtained for
      increasing fertility of the sperm used in artificial fertilization, diagnosis and
      treatment of male infertility.

PMID- 9577708
TI  - An outbreak of Rift Valley Fever, eastern Africa, 1997-1998.

PMID- 9577709
TI  - Recommendations on the disinsecting of aircraft.

PMID- 9577710
TI  - New impaired practitioner's program.

PMID- 9577711
TI  - Contracts voided for anti-kickback violations.

PMID- 9577712
TI  - Anyone for cloning?

PMID- 9577713
TI  - When and why do Virginians choose to terminate treatment?

PMID- 9577714
TI  - Diagnosis of stroke.
AB  - The determination that a patient has suffered a stroke is readily based on the
      clinical criteria along with the additional ancillary procedures discussed. The
      diagnosis is not complete, however, until the etiology has been found, for only
      then can rational therapy proceed.

PMID- 9577715
TI  - Anticoagulants and antiplatelet agents in acute ischemic stroke.

PMID- 9577716
TI  - Thrombolytic therapy for acute ischemic stroke.
AB  - The approval of thrombolytic therapy for acute stroke represents a revolution in
      the approach to treatment of acute stroke. For the first time there is a
      clinically proven therapy to improve outcome of acute ischemic stroke and this
      therapy is likely to be a harbinger of an entirely new era of acute therapies.
      The management of stroke now requires a rapid response involving a multi
      disciplinary team approach. The formation of Acute Stroke Intervention Teams and
      designated treatment centers will ensure that rapid, carefully administered acute
      stroke therapy is available to all eligible patients. The PCP has the invaluable
      role of not only promoting preventive care for cerebrovascular disease but also
      of educating patients on how to recognize the symptoms of stroke and providing
      guidance in obtaining appropriate acute therapies for stroke.

PMID- 9577717
TI  - Neuroprotective therapy in acute ischemic stroke.

PMID- 9577718
TI  - The current status of endovascular stroke therapy.

PMID- 9577719
TI  - The Stroke Team, An organized approach to identification and treatment of acute
      ischemic stroke patients.

PMID- 9577720
TI  - Closing the gap making use of primary prevention.

PMID- 9577722
TI  - Police officers' perceptions of eyewitness performance in forensic
      investigations.
AB  - Few contemporary data support the assertion that eyewitnesses are important in
      police investigations. In the present study, 159 UK police officers were surveyed
      regarding their perceptions of eyewitnesses and eyewitness performance. The
      respondents indicated that eyewitnesses usually provide the central leads in
      criminal investigations; however, the police officers also believed that
      eyewitnesses rarely provide sufficient information, especially descriptive
      details as opposed to action details. Nevertheless, the officers believed that
      eyewitnesses are rarely incorrect. A sizable minority reported that witnesses
      rarely come forward to the police and that those who do are often reluctant to
      testify in court. Many officers indicated that they do not have enough time to
      conduct good eyewitness interviews.

PMID- 9577721
TI  - Race and gender as components of the working self-concept.
AB  - A sample of 78 U.S. students carried beepers for 1 week and reported in situ on
      their awareness of gender and race. The participants to whom gender and race were
      more important were more aware of those characteristics, and their awareness of
      gender and race was more variable across situations. Awareness was higher in
      public than in private settings; it was also higher during athletic than during
      academic involvement. The White participants were more aware of race when they
      were in the racial minority; the non-White participants were more aware of race
      when they were in the racial majority. All the participants were more aware of
      gender when they were in the gender minority.

PMID- 9577723
TI  - The learning of Hebrew by Israeli Arab students in Israel.
AB  - The relationship was investigated between the attitudes and cultural backgrounds
      of Israeli Arab students and their reading comprehension of Jewish and Arab
      stories. The participants were 210 Israeli Arab students in the 10th grade. An
      attitude questionnaire, Arab and Jewish stories, multiple-choice questions about
      each story, and a semantic differential test for evaluating the stories'
      characters were used. The students scored higher on reading comprehension of
      texts from their own (Arab) culture than of texts from the unfamiliar (Jewish)
      culture. The motivation of the Arab students to learn Hebrew was primarily
      instrumental rather than integrative. The participants evaluated Jewish
      characters and their roles more negatively than they evaluated Arab characters in
      both the Jewish and Arab stories.

PMID- 9577724
TI  - Relationship of order and number of siblings to perceived parental attitudes in
      childhood.
AB  - Despite the increasingly recognized link between perceived parenting behavior and
      the onset of psychopathology in adults, studies of the possible determinants of
      perceptions of parenting behavior are rare. In a sample of 1,145 pregnant
      Japanese women, correlations were examined between the numbers and sexes of
      siblings and perceived rearing practices, as rated by the Parental Bonding
      Instrument (PBI; Parker, Tupling, & Brown, 1979). The participants with more
      elder sisters viewed their parents' attitudes as less caring, whereas those with
      more brothers, particularly younger brothers, viewed their parents' attitudes as
      less overprotective. However, the proportion of the variance of all the PBI
      scores explained by different types of siblings was very small.

PMID- 9577725
TI  - Eating disorders among Indian and Australian university students.
AB  - In a study of eating disorders, 297 Australian and 249 Indian university students
      completed the Eating Attitudes Test (EAT-26; Garner, Olmsted, Bohr, & Garfinkel,
      1982) and the Goldfarb Fear of Fat Scale (GFFS; Goldfarb, Dykens, & Gerrard,
      1985). Contrary to predictions, the Indian participants scored significantly
      higher than the Australian participants on both measures. The Indian women scored
      significantly higher than the Australian women on the EAT-26 but not on the GFFS.
      The Australian men showed significantly fewer symptoms than all other groups. The
      Indian men did not differ from the Australian or Indian women on either the EAT
      26 or GFFS. The urban Indians did not differ from their rural counterparts on the
      GFFS, but the rural Indians had significantly higher EAT-26 scores than the urban
      Indians.

PMID- 9577726
TI  - The effect of native-language retention and insecurity on Asian Indian fertility
      in the United States.
AB  - The relationship of social/psychological insecurity and native-language retention
      to fertility was explored among a nationally representative sample of 3,408
      endogamously wed Asian Indian women living in the United States. Native-language
      retention had a negative impact on Asian Indian women's fertility that cannot be
      explained by the normative dimension of the minority group status hypothesis
      (Goldscheider & Uhlenberg, 1969); therefore, alternative explanations for
      minority fertility differentials are required.

PMID- 9577727
TI  - The intention to give up smoking: disease versus social dimensions.
AB  - An expanded protection motivation model was used to investigate the intention to
      give up smoking. Because smoking has both physiological and social-psychological
      foundations, the model was expanded to include the social dimensions as well as
      the original disease dimensions as predictors of health behavior. The
      participants were 96 current smokers (35 male and 61 female) in Australia; 44
      were young adults (age < 22 years), and 52 were adults (age > 34 years). Data
      were analyzed by multiple regression with hierarchical entry, first of disease
      dimensions, then of social dimensions. For both the young and the adult smokers,
      the disease dimensions contributed significantly to the results of the regression
      equations. Addition of the social dimensions yielded a significant F change only
      for young smokers and increased the amount of variance explained from 23% to 38%.

PMID- 9577728
TI  - Motives for social decision-making strategies among Finnish and Estonian
      adolescents [corrected].
AB  - Justifications for aggression and withdrawal were compared between Finnish and
      Estonian adolescents. The former had grown up in a pluralistic Western culture;
      the latter, in a communist Soviet culture. After receiving a questionnaire with
      descriptions of 2 everyday social problems, teasing and backbiting, and a list of
      problem-solving strategies, the participants were asked how they would justify
      the use of each strategy. The Estonian participants more frequently chose
      instrumental justifications for aggression, whereas the Finnish participants
      tended to report that aggressive behavior was "fun." Aggression may be perceived
      as more deviant in Finland than in Estonia. Among the Finnish participants,
      withdrawal was motivated by a desire to avoid harm; among the Estonian
      participants, withdrawal reflected helplessness. The Estonian participants
      experienced cognitive dissonance between official education and the informal
      information learned in families; there was also dissonance between inner speech
      (banned history) and the official history taught in the schools.

PMID- 9577729
TI  - Blacks' and whites' perceptions of interracial and intraracial date rape.
AB  - The prevalence of rape myths contributes to victims' reluctance to report rapes.
      Black (n = 30) and White (n = 96) U.S. college students responded to the Rape
      Myth Scale (Burt, 1980) and read a scenario of an acquaintance rape; the race of
      the perpetrator and victim (Black or White) were varied. The respondents assessed
      the victim's and perpetrator's responsibility and evaluated the incident. As
      hypothesized, the respondents with strong beliefs in rape myths were more
      tolerant of the rapist and less tolerant of the victim than were those with
      weaker beliefs. There was limited support for the myth of the Black rapist and
      White victim; however, the myth of the Black rapist appeared particularly strong
      among the Black respondents. The women responded more negatively to the rapist
      and more positively to the victim than the men did. Such biases in attitudes
      toward rape could keep women from reporting rapes and accused rapists from
      receiving fair trials.

PMID- 9577730
TI  - An autophotographic study of poverty, collective orientation, and identity among
      street children.

PMID- 9577731
TI  - Personality correlates of adult attachment style.

PMID- 9577732
TI  - Stereotyping the nocturnal person: findings with some alarming implications.

PMID- 9577733
TI  - Sensitivity of primary screening by rapid review: 'to act or not to act on the
      results, that is the question'.

PMID- 9577734
TI  - The sensitivity of rapid (partial) review of cervical smears.
AB  - Rapid review involves a daily rapid (e.g. 30 s) review of all smears not normally
      double-screened. It has been suggested that the method may increase the
      sensitivity of cervical cytology by identifying abnormalities not reported on
      initial screening, true false negatives (TFN). Rapid screening is reported to
      have high sensitivity for cervical neoplasia when used as a preview tool. To be
      effective, however, in a review mode it must be able to detect TFN. Several
      studies have found that many TFN result from factors such as low numbers of
      abnormal cells or subtle expression of diagnostic criteria. Studies on the
      sensitivity of rapid screening for detecting TFN would therefore provide a more
      reliable estimate of its value as a review tool. The sensitivity of rapid re
      screening was evaluated using a test set of 200 cases. Each of 15 screeners
      rapidly reviewed (30 s partial screen) the set over a 2-week period. The set
      consisted of 129 normal, 28 low-grade squamous lesions (CIN I), 37 high-grade
      lesions (CIN II, III and adenocarcinoma in situ (AIS)) and six invasive
      carcinomas. The abnormals included 20 TFN cases. The median sensitivity for
      abnormalities was 62%. Rapid review was more sensitive for CIN II and CIN III
      (67%) and invasive carcinoma (66.7%) than for CIN I (53%). Great variation was
      apparent in the sensitivity for individual screeners, with a range of 41-86% for
      all abnormalities. The sensitivity for TFN cases varied even more (10-75%, median
      35%) and for most screeners was significantly (P < 0.05) lower than for cases
      which were detected on initial screen (53-90%, median 70.6%). Following this
      trial rapid review was used routinely for a period of 3 months. In this time
      11,413 cases were rapidly reviewed. This led to the full review of 415 slides
      (3.5%) and the identification of 16 cases of undetected CIN (12 CIN I, three CIN
      II, one CIN III). Based on current estimates of our laboratory false-negative
      rate this represents between a quarter and half of the TFN cases of CIN that
      probably occurred in this period. In conclusion, rapid screening is likely to be
      significantly less sensitive when used in a review rather than a preview mode. In
      routine practice the method requires a daily commitment of screener time, but
      does provide a higher yield of TFN smears than does random review, and allows
      amendment of these results prior to reporting.

PMID- 9577735
TI  - The correlation between the grade of dyskaryosis on cervical smear, grade of
      cervical intraepithelial neoplasia (CIN) on punch biopsy and the final
      histological diagnosis on cone biopsies of the cervix.
AB  - This study was carried out to assess how reliably a punch biopsy of the cervix
      predicts the maximum grade of CIN present and whether a colposcopically directed
      punch biopsy is more reliable than cytology in predicting the grade of
      intraepithelial neoplasia present in the cervix. The grade of CIN in 107 cone
      biopsy specimens was compared with the grade of CIN and dyskaryosis in punch
      biopsies and smears from the same patients. Exact correlations were identified
      between the highest grade lesions on cone biopsy and those in 63% of punch
      biopsies and 49% of cervical smears. We conclude that punch biopsy provides a
      more reliable estimate of the highest grade of CIN present in a subsequent cone
      biopsy than cervical cytology, but nonetheless fails to give a consistent
      estimate of the final grade of CIN in a significant percentage of cases.

PMID- 9577736
TI  - Cervical screening: management of patients referred for colposcopy with smear
      abnormalities less severe than dyskaryosis.
AB  - The cervical smear and biopsy results were reviewed for 141 patients who were
      referred for colposcopy with either a technically unsuitable smear or with
      cervical smear abnormalities less severe than dyskaryosis. The number of
      referrals due to minor smear abnormalities more than doubled from 8.6% to 22.3%
      of the total colposcopy referrals over the 4 year period studied. The minor smear
      abnormalities were only associated with cervical intraepithelial neoplasia (CIN)
      in patients aged < 50 years. In 19 (13.5%) of the 141 patients high-grade lesions
      (CIN II or CIN III) were diagnosed. There were no cases of invasive cancer.
      Furthermore, the increased number of patients being referred for colposcopy with
      minor cervical smear abnormalities highlights the increasing pressures on
      colposcopy services, with prolonged waiting times for all patients.

PMID- 9577737
TI  - Evaluation of cytological morphologic criteria and AgNOR expression in male
      breast lesions.
AB  - Fine needle aspiration (FNA) breast smears from 81 male patients have been
      examined in our laboratory between 1988 and 1994. The cytological criteria for
      diagnosing male breast lesions and the expression of nuclear organizer regions
      were evaluated. Of the 81 cases examined cytologically, 50 cases were proven
      cytologically and histologically to be inactive gynaecomastia, two cases showed
      florid gynaecomastia and there were 10 adenocarcinomas; in the 17 cases in which
      no cytological evidence of gynaecomastia or malignancy was found, the
      histological diagnosis was gynaecomastia in 13 and there was one case of
      mastopathy; in two cases suspicious of malignancy on cytology the histological
      examination proved to be florid gynaecomastia in one case and the other showed an
      adenocarcinoma. The absolute specificity of FNA in this study was 74.28%, the
      complete specificity 98.5%, the absolute sensitivity 90.9% and the complete
      sensitivity 100%. The overall accuracy was 97.5%, the positive predictive value
      91.66% and the negative predictive value 98.5%. In all cases of male breast
      carcinoma, AgNOR mean value was > or = 3; thus, it appears that AgNOR mean value
      3 could be used as a cut-off value between benign and malignant male breast
      lesions. Our experience suggests that FNA is an acceptable procedure for the
      investigation of male breast lesions.

PMID- 9577738
TI  - A comparative study of three variations of the learning vector quantizer in the
      discrimination of benign from malignant gastric cells.
AB  - A prospective study was undertaken to investigate the potential value of
      morphometry and artificial neural networks (ANN) for the discrimination of benign
      and malignant gastric lesions. Two thousand five hundred cells from 23 cases of
      cancer, 19 cases of gastritis and 58 cases of ulcer were selected as a training
      set, and an additional 8524 cells from an equal number of cases of cancer,
      gastritis and ulcer were used as a test set. Images of routine processed gastric
      smears stained by the Papanicolaou technique were processed by a custom image
      analysis system. The application of the learning vector quantization (LVQ)
      classifier enabled correct classification of > 97% of benign cells and > 95% of
      malignant cells, obtaining an overall accuracy of > 97%. This study presents the
      capabilities of ANN, and also indicates that ANN and image morphometry may offer
      useful information on the potential of malignancy in gastric cells.

PMID- 9577739
TI  - Fine needle aspiration (FNA) cytology in diagnosis of epidermoid cyst in testis.

PMID- 9577741
TI  - Granulocytic sarcoma of the breast diagnosed by fine needle aspiration (FNA)
      cytology.

PMID- 9577740
TI  - Laryngeal chondrosarcoma: fine needle aspiration (FNA) of an unusual tumour.

PMID- 9577742
TI  - Recommended code of practice for laboratories providing a cytopathology service.

PMID- 9577743
TI  - Adequacy of cervical smears.

PMID- 9577744
TI  - Rapid rescreening.

PMID- 9577745
TI  - Commentary: defining exposure and related concepts.

PMID- 9577746
TI  - Adjusting for temporal variation in the analysis of parallel time series of
      health and environmental variables.
AB  - Time series of daily administrative cardio-respiratory health and environmental
      information have been extensively used to assess the potential public health
      impact of ambient air pollution. Both series are subject to strong but unrelated
      temporal cycles. These cycles must be removed from the time series prior to
      examining the role air pollution plays in exacerbating cardio-respiratory
      disease. In this paper, we examine a number of methods of temporal filtering that
      have been proposed to eliminate such temporal effects. The techniques are
      illustrated by linking the number of daily admissions to hospital for respiratory
      diseases in Toronto, Canada for the 11 year period 1981 to 1991 with daily
      concentrations of ambient ozone. The ozone-hospitalization relationship was found
      to be highly sensitive to the length of temporal cycle removed from the admission
      time series, and to day of the week effects, ranging from a relative risk of
      0.874 if long wave cycles were not removed at all to 1.020 for models which
      removed at least cycles greater than or equal to one month based on the
      interquartile pollutant range. The specific statistical method of adjustment was
      not a critical factor. The association was not as sensitive to removal of cycles
      less than one month, except that negative autocorrelation increased for series in
      which cycles of one week or less were removed. We recommend three criteria in
      selecting the degree of smoothing in the outcome: removal of temporal cycles,
      minimizing autocorrelation and optimizing goodness of fit. The association
      between ambient ozone levels and hospital admissions for respiratory diseases was
      also sensitive to the season of examination, with weaker associations observed
      outside the summer months.

PMID- 9577747
TI  - Population exposure to radioactivity from consumption of caribou among the
      Dene/Metis of Denendeh (western Northwest Territories, Canada).
AB  - There has been long-standing concern with exposure to radioactivity through the
      consumption of caribou, particularly in indigenous populations in the western
      Northwest Territories, Canada, who are traditionally high consumers. We conducted
      a dietary survey in this region in 1994 to estimate population exposure levels.
      Dietary information was collected from 1012 individuals in sixteen communities
      (1012 days of 24-hour dietary recalls, 1012 food frequency questionnaires) and
      radionuclide levels in caribou flesh, liver and kidneys were measured. Monte
      Carlo statistical methods were employed to integrate these data sets and estimate
      the distribution of radiation exposure for people in five regions (Gwich'in,
      Sahtu, Dogrib, Deh-Cho, South Slave). The exposure levels were highest in the
      South Slave region and in older males (40+ years), and lowest in the Gwich'in
      region and in younger females (20-40 years). Median exposure level ranged from
      0.95 to 5.31 mSv per year (mean of medians = 2.96 mSv/y). In each group the 95th
      percentile of exposure was 2-3 times greater than the median. These exposure
      levels are comparable to exposure levels in Alaskan Eskimos and Marshall Island
      residents, and are much higher than European or American urban populations.
      Caribou meat is a very nutritious food. We conclude that, although there is some
      radiation exposure from consuming caribou, the associated health risks are low
      and are outweighed by the physical, social and cultural benefits derived from
      hunting and eating caribou.

PMID- 9577748
TI  - Exposure to carbon monoxide, methyl-tertiary butyl ether (MTBE), and benzene
      levels inside vehicles traveling on an urban area in Korea.
AB  - This study was designed to allow systematic comparison of exposure on public (40
      seater buses) and private (four passengers cars) transport modes for carbon
      monoxide (CO), methyl-tertiary butyl ether (MTBE), and benzene by carrying out
      simultaneous measurements along the same routes. There were statistically
      significant differences (p < 0.05) in the concentrations of all target compounds
      among the three microenvironments; inside autos; inside buses; and in ambient
      air. The target compounds were significantly correlated for all the three
      environments, with at least p < 0.05. The in-vehicle concentrations of MTBE and
      benzene were significantly higher (p < 0.0001), on the average 3.5 times higher,
      in the car with a carbureted engine than in the other three electronic fuel
      injected cars. On the other hand, the CO concentrations were not significantly
      different among the four cars. The in-auto MTBE levels (48.5 micrograms/m3 as a
      median) measured during commutes in this study was 2-3 times higher than the New
      Jersey and Connecticut's results. The in-auto concentration of CO (4.8 ppm as a
      median) in this study was comparable with those in later studies in some American
      cities, but much lower than those in earlier studies in other American cities.
      The in-bus CO concentration was 3.6 ppm as a median. As a median, the in-auto
      concentration of benzene was 44.9 micrograms/m3, while the in-bus concentration
      17.0 micrograms/m3. The in-auto/in-bus exposure ratios for all the target
      compounds was 31-40% higher than the corresponding concentration ratios, due to
      the higher travel speed on buses in the specified commute route as compared to
      the autos.

PMID- 9577749
TI  - Relationship between soil and dust lead in a lead mining area and blood lead
      levels.
AB  - The relationship between lead mining waste and childhood lead poisoning is poorly
      understood. This study evaluates the contribution of soil lead to blood lead
      levels. METHODS: 125 children between 6 and 71 months of age living in a lead
      mining area of southwestern Missouri were evaluated for blood lead and their
      homes tested for lead in soil, dust, and paint. These results were compared to 26
      control children. RESULTS: Homes in the lead mining area had significantly
      increased soil and dust lead levels and significantly higher blood lead levels.
      The primary source of dust lead was soil lead. There was a strong relationship
      between blood lead levels and dust, soil, and paint lead. CONCLUSION: Soil lead
      related to mining operations plays a significant role in contributing to blood
      lead levels in children.

PMID- 9577750
TI  - A model to evaluate past exposure to 2,3,7,8-TCDD.
AB  - Data from several studies suggest that concentrations of dioxins rose in the
      environment from the 1930s to about the 1960s/70s and have been declining over
      the last decade or two. The most direct evidence of this trend comes from lake
      core sediments, which can be used to estimate past atmospheric depositions of
      dioxins. The primary source of human exposure to dioxins is through the food
      supply. The pathway relating atmospheric depositions to concentrations in food is
      quite complex, and accordingly, it is not known to what extent the trend in human
      exposure mirrors the trend in atmospheric depositions. This paper describes an
      attempt to statistically reconstruct the pattern of past human exposure to the
      most toxic dioxin congener, 2,3,7,8-TCDD (abbreviated TCDD), through use of a
      simple pharmacokinetic (PK) model which included a time-varying TCDD exposure
      dose. This PK model was fit to TCDD body burden data (i.e., TCDD concentrations
      in lipid) from five U.S. studies dating from 1972 to 1987 and covering a wide age
      range. A Bayesian statistical approach was used to fit TCDD exposure; model
      parameters other than exposure were all previously known or estimated from other
      data sources. The primary results of the analysis are as follows: (1) use of a
      time-varying exposure dose provided a far better fit to the TCDD body burden data
      than did using a dose that was constant over time; this is strong evidence that
      exposure to TCDD has, in fact, varied during the 20th century, (2) the year of
      peak TCDD exposure was estimated to be in the late 1960s, which coincides with
      peaks found in sediment core studies, (3) modeled average exposure doses during
      these peak years was estimated at 1.4-1.9 pg TCDD/kg-day, and (4) modeled
      exposure doses of TCDD for the late 1980s of less than 0.10 pg TCDD/kg-day
      correlated well with recent estimates of exposure doses around 0.17 pg TCDD/kg
      day (recent estimates are based on food concentrations combined with food
      ingestion rates; food is thought to explain over 90% of total dioxin exposure).
      This paper describes these and other results, the goodness-of-fit between
      predicted and observed lipid TCDD concentrations, the modeled impact of breast
      feeding on lipid concentrations in young individuals, and sensitivity and
      uncertainty analyses.

PMID- 9577751
TI  - Environmental radiation levels in central Florida's phosphate mining district.
AB  - Environmental levels of radionuclides and gamma radiation were measured in two
      communities located near active phosphate mining areas in Florida. Activated
      carbon canisters and alpha track detectors were used to measure indoor air levels
      of radon in approximately 100 private homes. Elevated levels of radon (> 4
      picocuries per liter [pCi/L]) were detected in 8 of 27 homes in a community built
      on reclaimed land that had been previously mined. In a nearby community built on
      unmined land, elevated levels of radon were detected in 1 of 69 homes. All of the
      homes with elevated levels of radon were built on concrete slabs. Outdoor gamma
      radiation levels were significantly greater in the reclaimed area than in the
      unmined area. Air particulates collected from outdoor ambient air at three
      locations did not contain elevated levels of radionuclides.

PMID- 9577753
TI  - A system linking occupation history questionnaire data and magnetic field
      monitoring data.
AB  - A method is presented which links on-site electromagnetic field monitoring data
      with pre-existing work history data. The linkage is used to estimate cumulative
      and average annualized magnetic field exposure for a case-control study. On-site
      electromagnetic field monitoring data for 1,966 volunteer utility employees, at
      59 sites in the United States and three other countries, were obtained from a
      large project (the EMDEX project) designed to collect, analyze, and document 60
      Hz electric and magnetic field exposures for a diverse population. These data
      represent 9 primary work environments, and 16 job classification categories,
      amounting to 144 unique job categories which were consolidated using the job
      exposure matrix presented into 282 three-digit Dictionary of Occupational Title
      (DOT) codes. The DOT code categories were then linked to lifetime occupational
      histories from a case-control study of leukemia. The method may be extended to
      link additional job titles with monitoring information. Job titles linked with
      electromagnetic field monitoring information provide more specific estimates of
      exposure intensity than previous ordinal estimates of exposure. Therefore,
      estimates of cumulative electromagnetic field exposure are achievable, as well as
      high and low level exposure estimates.

PMID- 9577752
TI  - Airborne exposures to PAH and PM2.5 particles for road paving workers applying
      conventional asphalt and crumb rubber modified asphalt.
AB  - Personal exposure monitoring was conducted for road paving workers in three
      states. A research objective was to characterize and compare occupational
      exposures to fine respirable particles (< 2.5 microns) and particle-bound
      polycyclic aromatic hydrocarbons (PAHs) for road paving workers applying
      conventional (petroleum derived) asphalt and asphalt containing crumb rubber from
      shredded tires. Workers not exposed to asphalt fume were also included for
      comparison (to support the biomarker component of this study). The rubber content
      of the crumb rubber modified (CRM) asphalt at the three study sites was 12, 15,
      and 20%. A comparison of some specific job categories from two sites indicates
      greater potential carcinogenic PAH exposures during CRM asphalt work, however,
      the site with the greatest overall exposures did not indicate any differences for
      specific jobs. A statistical analysis of means for fine particle, pyrene and
      total carcinogenic PAH personal exposure shows, with two exceptions, there were
      no differences in exposures for these three measurement variables. One site shows
      significantly elevated pyrene exposure for CRM asphalt workers and another site
      similarly shows greater carcinogenic PAH exposure for CRM asphalt workers.
      Conventional and CRM asphalt worker airborne exposures to the PAH carcinogen
      marker, BaP, were very low with concentrations comparable to ambient air in many
      cities. However, this study demonstrates that asphalt road paving workers are
      exposed to elevated airborne concentrations of a group of unknown compounds that
      likely consist of the carcinogenic PAHs benz(a)anthracene, chrysene and
      methylated derivatives of both. The research described in this article has been
      reviewed in accordance with U.S. Environmental Protection Agency policy and
      approved for publication. Mention of trade names or commercial products does not
      constitute endorsement or recommendation for use.

PMID- 9577754
TI  - Initial uptake kinetics in human skin exposed to dilute aqueous trichloroethylene
      in vitro.
AB  - In vitro uptake of 14C-labeled trichloroethylene (TCE) from dilute (approximately
      5-ppb) aqueous solutions into human surgical skin was measured using accelerator
      mass spectrometry (AMS). We analyzed 105 breast-tissue samples obtained from
      three subjects, representing 27 separate exposure experiments conducted at
      approximately 20 degrees C for 0, 1, 5, 15, 30, or 60 min. The AMS data obtained
      positively correlate with (p approximately 0) and vary significantly nonlinearly
      with (p = 0.0094) exposure duration. These data are inconsistent (p approximately
      0) with predictions made for TCE by a proposed U.S. Environmental Protection
      Agency (USEPA) dermal-exposure model, even when uncertainties in its recommended
      parameter values for TCE are considered, but are consistent (p = 0.17) with a 1
      compartment model for exposed skin-surface tissue governed in vitro by a maximum
      effective permeability of K*p = 0.28 cm h-1 (+/- 7.0%) and a first-order rate
      constant of k1 = 1.2 h-1 (+/- 16%). The apparent compartment depth is estimated
      to be approximately 40-100 microns, i.e., to comprise much or all of the
      epidermis. In contrast, the USEPA model implies only negligible TCE penetration
      beyond SC during a 1-h exposure. The K*p estimate based on the 1-compartment
      model fit is consistent with estimates for TCE based on in vivo studies, which
      supports the hypothesis that the USEPA model underpredicts short-term dermal
      uptake of TCE from water. It is shown that for humans, this fit also implies that
      normalized total uptake of TCE from water by short-term dermal contact in vivo is
      predicted to be fK*p, where f is approximately 80% for longer normothermic
      exposures and approximately 95% during a brief hot shower or bath. This study
      illustrates the power of AMS to facilitate analyses of contaminant
      biodistribution and uptake kinetics at very low environmental concentrations.

PMID- 9577755
TI  - What is your diagnosis? Renal lymphoma in a cat.

PMID- 9577757
TI  - Use of ticarcillin in the management of canine otitis externa complicated by
      Pseudomonas aeruginosa.
AB  - Twelve dogs were referred with purulent and proliferative otitis externa. Prior
      treatment included fluoroquinolones, glucocorticoids and polyvalent ear drops
      over seven days to five months. In all cases the vertical and horizontal ear
      canals were inflamed and thickened, with ruptured tympanic membranes in four
      cases. No abnormalities were seen on radiography of the osseous bullae. Numerous
      rod bacilli and degenerate neutrophils were seen on cytology. Pseudomonas
      aeruginosa resistant to fluoroquinolones and gentamicin was cultured in all
      cases. Treatment was initiated with 1 to 2 mg/kg prednisolone per os once daily,
      and a cleansing and drying ear cleaner followed by topical administration of
      injectable ticarcillin solution four times daily. Cases with ruptured tympanae
      also received 15 to 25 mg/kg ticarcillin three times daily intravenously until
      the membranes had healed. All cases were anaesthetised for repeated saline ear
      flushes until no further discharge was evident and no rods were seen on cytology.
      Topical ticarcillin and the ear cleaner were continued twice daily for 14 days
      after clinical resolution. The duration of treatment ranged from 14 to 36 days.
      Treatment was withdrawn in one case which developed a drug reaction. All other
      cases responded well with no adverse effects.

PMID- 9577758
TI  - Comparison of two classification protocols in the evaluation of elbow dysplasia
      in the dog.
AB  - The incidence of elbow disease based solely on arthrosis (ARTH) score was
      compared with a protocol using a combination of ARTH score plus a score for
      primary lesions (ED score). The population of dogs studied included 425 Bernese
      mountain dogs and 22 dogs of other breeds. The overall agreement between the two
      systems was high. However, 12 per cent of ARTH-score negative cases were positive
      using the ED score. This difference was statistically significant (P < 0.005).
      The female:male ratio of the dogs missed using the ARTH score was 2:1. The
      proportion of dogs affected with arthrosis increased with age, male dogs being
      affected more frequently. The development of arthrosis depends not only on age
      and breed, but probably also on gender. Thus, screening for elbow dysplasia
      should be based on at least two radiographic projections, including arthrosis and
      primary lesions. As the vast majority of dogs in this study were Bernese mountain
      dogs, conclusions are valid only for this breed.

PMID- 9577756
TI  - Comparison of carprofen and pethidine as postoperative analgesics in the cat.
AB  - The postoperative analgesia and sedation in cats given carprofen (4.0 mg/kg
      bodyweight by subcutaneous injection preoperatively) was compared to that in cats
      given pethidine (3.3 mg/kg bodyweight by intramuscular injection postoperatively)
      in a controlled, randomised, blinded, multicentre clinical trial. Further dosing
      with the particular analgesic was allowed if a cat was exhibiting unacceptable
      pain. In total, 57 carprofen cases and 59 pethidine cases were evaluated.
      Significantly fewer cats in the carprofen group required additional doses of
      analgesic, and mean pain scores were significantly lower from four hours after
      ovariohysterectomy, and at 18 to 24 hours after castration, compared to the
      pethidine group. In conclusion, carprofen provided as good a level of
      postoperative analgesia as pethidine, but of a longer duration (at least 24
      hours) and was well tolerated. It thus provides an option for 'pre-emptive
      analgesia' in cats about to undergo surgery.

PMID- 9577759
TI  - Hyperadrenocorticism in six cats.
AB  - The case records of six cats with hyperadrenocorticism presented to the
      Department of Clinical Veterinary Medicine, University of Cambridge, over an 11
      year period were reviewed. Signalment and clinical signs were similar to previous
      reports but, in contrast to other reports, only three cats had diabetes mellitus
      on presentation. Abdominal radiographs revealed an adrenal mass in one case,
      obesity in all cases but no hepatomegaly. The adrenal glands were identified
      ultrasonographically in three out of six cases. Clinicopathological findings were
      non-specific. The diabetic cats had a significantly lower serum potassium
      concentration than the non-diabetic cats (P < 0.05). Results of
      adrenocorticotrophic hormone (ACTH) stimulation tests were supportive of a
      diagnosis of hyperadrenocorticism in the five cats in which they were performed.
      Five cats had pituitary-dependent hyperadrenocorticism (PDH) and one had an
      adrenal tumour. Differentiation between the two forms of hyperadrenocorticism was
      possible preoperatively in five out of six cats. Adrenal histopathology confirmed
      hyperplasia in four cats and adenocarcinoma in one cat. Three cats with PDH
      underwent bilateral adrenalectomy and two of these cats had low, flat ACTH
      stimulation tests postoperatively and survived for significant periods. The cat
      with an adrenal tumour underwent partial unilateral adrenalectomy, maintained a
      positive ACTH stimulation test postoperatively and was euthanased one week after
      surgery.

PMID- 9577760
TI  - Risk factors for gastric dilatation in Irish setter dogs.
AB  - Questionnaires were used to obtain data about Irish setters with gastric
      dilatation (GD) and control Irish setters. The risk of GD increased with age (P <
      0.01) but was not associated with gender. Age and gender-matched controls were
      compared with cases (n = 74). Predisposing risks were aerophagia (unadjusted odds
      ratio 12.44, P < 0.001), a single food type (adjusted odds ratio 3.15, P < 0.01)
      and feeding once daily (adjusted odds ratio 2.90, P < 0.02). Apparent risk from a
      dry food diet and a condition score of less than 2 was not confirmed by logistic
      regression. Precipitating risks were recent kennelling (unadjusted odds ratio
      100, P < 0.005) or a car journey (unadjusted odds ratio 3.29, P < 0.025). No risk
      was attributed to intensity or duration of exercise, temperament, appetite, speed
      of eating, vomiting or diarrhoea.

PMID- 9577762
TI  - Treatment of patent ductus arteriosus by placement of two intravascular
      embolisation coils in a puppy.
AB  - A 14-week-old border collie with a history of exercise intolerance was confirmed
      to have a patent ductus arteriosus (PDA) from colour flow Doppler
      echocardiography. Under general anaesthesia, angiography was performed to gauge
      accurately the width of the ductus, and then two intravascular embolisation coils
      were introduced into the ductus via percutaneous catheterisation of the femoral
      vein. The coils were both 8 mm in diameter, each with four loops. This led to an
      immediate disappearance of the murmur. Some slight residual flow was detected at
      the time of the procedure by angiography, but by 10 days postoperatively there
      was no PDA flow detectable. The time taken to complete the procedure was 55
      minutes, with a total fluoroscopy time of 15 minutes. Placement of intravascular
      embolisation coils represents a viable alternative to traditional surgical
      methods of ductus closure.

PMID- 9577761
TI  - Placement of a low-profile duodenostomy and jejunostomy device in five dogs.
AB  - Five male crossbred dogs successfully underwent surgical placement of button
      enterostomy tubes to evaluate the placement technique, maintenance and
      complications of these tubes. Surgical placement was quick, technically
      straightforward and similar to techniques used for other feeding tubes. None of
      the dogs experienced life-threatening complications during the 10 month follow-up
      period. One device required replacement as it was removed by the dog before a
      permanent fistula had formed. Open tubes due to loose safety plugs and focal
      cellulitis surrounding the exit sites of these tubes were noted in all dogs. The
      button tube may be a feasible option for long-term nutritional support in
      patients with pancreatic, hepatobiliary or gastrointestinal conditions.

PMID- 9577763
TI  - Multiple digital tumours in a rottweiler.
AB  - An eight-and-a-half-year-old rottweiler bitch was examined on four separate
      occasions over a period of 32 months for lameness caused by a mass on a digit. On
      each occasion the mass and affected digit were amputated. Three different
      neoplasms were diagnosed: two squamous cell carcinomas, a melanocytoma and an
      intracutaneous cornifying epithelioma. There was no recurrence following surgical
      excision.

PMID- 9577764
TI  - Haemophagocytic syndrome with disseminated intravascular coagulation in a dog.
AB  - Clinical signs and haematological abnormalities of haemophagocytic syndrome of
      unknown origin are described for a male, nine-year-old rottweiler referred
      because of weakness, depression, mild weight loss and relapsing fever. Mucous
      membranes were pale and the spleen was enlarged. Ultrasonography revealed diffuse
      irregular structures in the enlarged spleen, and cytological examination of
      multiple fine needle aspirates of the spleen demonstrated extramedullary
      haematopoiesis. Haematological examination revealed pancytopenia and disseminated
      intravascular coagulation. A bone marrow smear contained numerous marrow
      macrophages with a cytologically benign appearance, containing phagocytosed
      haematopoietic cells. The dog died one week after referral. The differential
      diagnosis is discussed.

PMID- 9577765
TI  - Series of pancreatitis cases.

PMID- 9577766
TI  - Feline immunodeficiency virus (FIV)

PMID- 9577767
TI  - Inside story: European Affairs Committee.

PMID- 9577768
TI  - The initial impact of rabbit hemorrhagic disease on European rabbit populations
      in South Australia.
AB  - The calicivirus agent for rabbit hemorrhagic disease (RHD) escaped from an island
      quarantine station to the Australian mainland in October 1995. Within 2 wk it was
      detected at an established field study site where wild European rabbits
      (Oryctolagus cuniculus) were being monitored in the Flinders Ranges National Park
      (South Australia, Australia). During November 1995, RHD reduced the rabbit
      numbers on the site by 95%. Approximately 3% of the population survived challenge
      by RHD and developed antibodies. Most of the antibody-positive survivors were 3-
      to 7-wk-old when challenged. Many rabbits died underground, but counts of rabbit
      carcasses found on the surface indicated that approximately 1 million rabbits had
      died above ground in the National Park, and that > 30 million rabbits may have
      died in adjacent areas during the November epidemic.

PMID- 9577769
TI  - First North American field release of a vaccinia-rabies glycoprotein recombinant
      virus.
AB  - Following nearly 10 yr of extensive laboratory evaluation, a vaccinia-rabies
      glycoprotein (V-RG) vaccine was the first recombinant virus to undergo limited
      North American field release on 20 August 1990. The free-ranging raccoon
      population on Parramore Island (Virginia, USA) was exposed to a high density (10
      baits/ha) of vaccine-laden baits distributed on a 300 ha vaccination area. An
      annual total of 887 raccoons were live-trapped for sedation, physical examination
      and blood collection for rabies antibody determination; there was no evidence of
      adverse effects or lesions due to the vaccine. Age and sex distributions, mean
      body weights, and live-capture histories of raccoons from the vaccination and non
      baited control areas were compared. There were no statistically significant
      differences in survivorship between the baited and non-baited areas, nor between
      rabies antibody-positive and antibody-negative raccoons from the vaccination
      area. There was no trend in field mortality that suggested an association with
      either tetracycline or sulfadimethoxine, used as biomakers, or with vaccine
      contact determined by antibody status. No gross or histopathologic lesions due to
      the vaccine were demonstrated among a subsample of live-trapped raccoons
      collected for gross necropsy, biomarker analysis, histopathologic examination,
      and V-RG virus isolation attempts. Recovery of V-RG virus was limited to the
      tonsils of two biomarker-positive, clinically healthy raccoons collected from the
      vaccination area for postmortem examination on days 2 and 4 following bait
      distribution. These data reinforce the extensive body of safety data on the V-RG
      virus and extend it to include field evaluation where vaccine is offered free
      choice in abundance, in baits designed to attract free-ranging raccoons, in a
      relatively simple ecosystem.

PMID- 9577771
TI  - Pseudorabies in the European wild boar from eastern Germany.
AB  - Sera collected from European wild boar (Sus scrofa) shot in Eastern Germany
      between January 1991 and December 1994 were tested for antibodies to pseudorabies
      virus (PRV). Of 3,143 sera tested, 281 (8.9%) and 13 (0.4%) were positive and
      suspect in an enzyme-linked immunosorbent assay (ELISA), respectively. The
      specificity of the reactions was confirmed by detection of neutralizing
      antibodies in 220 sera (74.8%) and by immunoblotting. Analysis of host age and
      sex of the animals, temporal and spatial factors showed significantly higher
      seroprevalences in older animals than in younger individuals, but no differences
      between males and females. Pseudorabies virus infections have been endemic in
      this wild boar population for several years and the extreme eastern part of the
      study area had significantly higher seroprevalences (< or = 22%) than other
      areas. In the area covered by this study, pseudorabies virus was eradicated in
      the domestic animal populations in 1985. Thus, the infections in the wild boar
      population appear to be endemic and persist completely separately and without
      affecting the domestic pig population.

PMID- 9577770
TI  - Serosurvey for orthopoxviruses in rodents and shrews from Norway.
AB  - Two hundred and twenty one blood samples representing eight different rodent
      species and the common shrew (Sorex araneus), collected in Norway between 1993
      and 1995, were examined for anti-orthopoxvirus antibodies by a competition enzyme
      linked imunnosorbent assay (ELISA) and, when possible, an indirect
      immunofluorescence assay. The serological results indicated that the bank vole
      (Clethrionomys glareolus), woodmouse (Apodemus sylvaticus) and Norway lemming
      (Lemmus lemmus) may be reservoir species for orthopoxviruses in Norway, with
      antibody prevalences of 17 (12/69), 30 (24/81) and 56% (19/34), respectively.
      Orthopoxvirus infection in lemmings has not been reported previously. On some
      other small rodent species such as field voles (Microtus agrestis), common rats
      (Rattus norvegicus), and common shrews, seropositive individuals were detected.
      However, the total number of tested animals was low, and the role of these
      species in the epidemiology of orthopoxvirus infections remains unclear. Attempts
      to isolate orthopoxviruses from these small mammals failed, although
      orthopoxvirus specific DNA sequences were detected previously in the same animals
      by the polymerase chain reaction (PCR). The serological results were compared
      with and discussed in the context of the occurrence of orthopoxvirus-specific DNA
      sequences, and it is concluded that orthopoxviruses are widely distributed among
      wildlife in Norway.

PMID- 9577772
TI  - Viral antibodies in coyotes from California.
AB  - Prevalence of antibodies against canine parvovirus (CPV), canine distemper virus
      (CDV), and canine adenovirus type 1 (CAV) were determined among 152 coyotes
      (Canis latrans) at the Naval Petroleum Reserves (NPRC; California, USA) from 1985
      to 1990. Overall prevalence of antibodies to CPV, CDV, and CAV was 66%, 37%, and
      68%, respectively. Prevalence of CPV and CDV varied significantly among years.
      Antibody prevalence did not differ between sexes for any disease, but did vary
      significantly among age classes and was lowest for pups (< 1-yr-old). Among pups,
      antibody prevalence increased with age for all three diseases. Coyotes are a
      potential source of viral exposure for endangered San Joaquin kit foxes (Vulpes
      macrotis mutica), but variation in coyote abundance did not appear to influence
      antibody prevalence among kit foxes.

PMID- 9577773
TI  - Epidemic mycoplasmal conjunctivitis in house finches from eastern North America.
AB  - In the winter of 1993-94, house finches (Carpodacus mexicanus) with severe
      conjunctivitis (later shown to be caused by Mycoplasma gallisepticum) were first
      observed in sub-urban Washington D.C. (USA) and adjacent states. Using a large
      network of volunteer observers in eastern North America, we were able to track
      the monthly prevalence of the disease between November 1994 and March 1997. Using
      the information on 24,864 monthly data forms, we describe the very rapid spread
      of the conjunctivitis epidemic through the eastern house finch population. The
      epidemic first expanded mainly north, probably carried along by house finches on
      their return migration, then mainly toward the southeast, and later west. By
      March 1997, conjunctivitis had been reported from most of the eastern range of
      the house finch. The prevalence of the disease seemed to fluctuate seasonally
      with increases in the fall, probably as a result of dispersing juveniles. House
      finch numbers decreased throughout winter in areas with cold winters and high
      conjunctivitis prevalence, suggesting significant mortality associated with the
      disease.

PMID- 9577774
TI  - Risk factors associated with mycoplasmal conjunctivitis in house finches.
AB  - Observations from a citizen-based survey were used to identify potential risk
      factors associated with mycoplasmal conjunctivitis (Mycoplasma gallisepticum) in
      eastern house finches (Carpodacus mexicanus). Between November 1994 and October
      1996, 778 volunteers provided 7,224 monthly observations at residential bird
      feeding sites across an eight state region in the eastern USA. Information
      collected by questionnaires included health status of house finches and four
      sympatric passerine species, types and number of bird feeders maintained,
      neighborhood housing locale and altitude of the observation site. Bivariate
      analyses revealed that house finches were 14 to 72 times as likely to be observed
      with conjunctivitis than the sympatric species studied. Year of the study,
      season, and the presence of platform, hopper, and tube type feeders were
      significantly associated with conjunctivitis in house finches. Multivariate
      analysis using a logistic regression model suggests that increased risk of
      conjunctivitis in house finches was associated with the second year of the study
      (the third year of the outbreak), the cooler non-breeding periods from September
      through March, and the presence of tube style feeders. In addition, the presence
      of raised platform type feeders may have been protective against conjunctivitis
      in house finches. Prevention of spread of this disease may include modifying bird
      feeding activities based on season and type of feeder.

PMID- 9577776
TI  - Growth of Cowdria ruminantium in tissue culture endothelial cell lines from wild
      African mammals.
AB  - Endothelial cell cultures were established from several wild African mammalian
      species. Long-term cultures were established from three ruminants, stable
      antelope (Hippotragus niger), buffalo (Syncerus caffer), and eland (Tragelaphus
      oryx), and from an omnivore, the bushpig (Potamochoerus porcus). Cowdria
      ruminanntium was isolated from plasma of clinically affected animals in these
      four cell lines and in bovine endothelial cells used routinely for C. ruminantium
      propagation. Nineteen different strains of C. ruminantium from Africa and the
      Caribbean region were grown and maintained in these cell lines and their growth
      was comparable with growth in the bovine endothelial cells. The role of sable
      antelope, eland, and bushpigs in the epidemiology of heartwater is unknown.
      However, these results extend the number of cell lines that can be used to
      isolate and grow C. ruminantium.

PMID- 9577775
TI  - Natural Mycoplasma gallisepticum infection in a captive flock of house finches.
AB  - Naturally-occurring mycoplasmal conjunctivitis is described among 104 wild
      caught, and initially seronegative, house finches (Carpodacus mexicanus)
      maintained in captivity for 12 wk during November 1995 through January 1996.
      Finches housed in three pens were monitored for clinical signs, and > or = 10
      birds were euthanatized for necropsy and mycoplasma testing every 2 wk. Within 2
      to 4 wk following initial detection of lesions, > 50% of the birds in each of
      three pens developed a debilitating disease characterized by mild to severe
      ocular swelling, conjunctivitis, and ocular and nasal discharge. Microscopic
      lesions in affected finches consisted of mild to severe lymphoplasmacytic
      inflammation with epithelial and lymphoid hyperplasia in conjunctivae, nasal
      turbinates, and trachea. Mycoplasma gallisepticum infection was confirmed by
      culture or polymerase chain reaction (PCR) in all birds with conjunctival lesions
      and in 43% of birds without lesions. An arbitrary primer PCR was used to confirm
      M. gallisepticum isolates as identical to a field strain previously associated
      with house finch conjunctivitis. Most birds (89%) with conjunctivitis developed a
      concurrent antibody response detectable by serum plate agglutination (SPA) within
      2 wk of lesion development. Hemagglutination inhibition (HI) and enzyme-linked
      immunosorbent assay (ELISA) tests were less sensitive than the SPA test. The
      clinical severity of this disease and high proportion of affected birds suggests
      that M. gallisepticum may have a negative impact on free-flying house finch
      populations.

PMID- 9577777
TI  - Isolation of Bartonella spp. from embryos and neonates of naturally infected
      rodents.
AB  - Embryos and neonatal offspring of wild-captured cotton rats (Sigmodon hispidus)
      and white-footed mice (Peromyscus leucopus) were tested for the presence of
      Bartonella spp. Isolates of Bartonella spp. were obtained from 18 of 31 embryos
      and 7 of 19 neonates from bacteremic dams of the two species; no isolates were
      obtained from material from non-bacteremic dams. Sequence analysis demonstrated
      that the isolates from embryos and neonates matched the phylogenetic group of
      Bartonella spp. isolates obtained from the mother. No antibodies to homologous
      Bartonella spp. antigens were detected in maternal and neonatal blood or
      embryonic tissue. These findings suggest the possibility of vertical transmission
      of Bartonella spp. among natural rodent hosts.

PMID- 9577778
TI  - Coxiellosis in domestic and wild birds from Japan.
AB  - Serological evidence of infection with Coxiella burnetii was found in 41 (2%) of
      1,951 domestic birds and in 167 (19%) of 863 wild birds from 17 and 5 prefectures
      in Japan, respectively, by microagglutination (MA) test. The bacteriological
      evidence of the infection was found in 17 (41%) of 41 domestic birds and 37 (22%)
      of 167 wild birds by the nested polymerase chain reaction (PCR). In addition, C.
      burnetii was isolated from five each of serum, spleen and fecal specimens from
      five jungle crows (Corvus macrorhynchos) (whose sera were positive by both the MA
      test and PCR) by inoculating laboratory mice. Domestic quail (Coturnix coturnix
      japonica) (3%), domestic muscovy ducks (Cairina moschata) (3%), domestic chickens
      (2%), domestic mallards (Anas platyrhynchos domesticus) (2%), carrion crows
      (Corvus corone) (37%), jungle crows (35%), and wild rock doves (Columba livia)
      (6%) showed serologic evidence of experience with C. burnetii. There was a
      tendency for a high prevalence among birds living and/or feeding in close
      proximity to infected livestock. This suggests that these birds are one of the
      less important links in maintaining the whole cycle of C. burnetii infection.

PMID- 9577779
TI  - Gastric spiral bacteria and intramuscular sarcocysts in African lions from
      Namibia.
AB  - Six juvenile male, one adult male, and three adult, female African lions
      (Panthera leo) from Etosha National Park, Republic of Namibia were presented for
      necropsy. Two of four adults and one of six juveniles had moderate numbers of
      gastric spiral bacteria. Additionally, four of four adults had sarcocysts. All
      juveniles had enteric Sarcocystis sp. oocysts, but no sarcocysts. The gastric
      spiral bacteria were located extracellularly in fundic and pyloric glands, and
      also apparently intracellularly within parietal cells in the fundic region. The
      organisms were 4 to 8 microns long, 0.63 micron wide, with a periodicity of 0.60
      micron. The bacteria had blunted ends with multiple flagella. No periplasmic
      fibrils were observed. The histologic and ultrastructural characteristics of the
      bacteria were considered most consistent with species in the genus Helicobacter
      or incompletely identified Helicobacter-like organisms. Gastric inflammation did
      not differ significantly between infected and uninfected individuals. The
      bacteria may be commensals, or an opportunistic pathogen. The sarcocysts were
      observed in hindlimb skeletal muscle of four individuals, with one individual
      also containing a single sarcocyst within glossal musculature. All observed cysts
      were mature, and were contained within individual myocytes. The cyst wall
      consisted of a 44 to 66 nm, granular, electron dense parasitophorous membrane
      with subjacent, 0.8 to 1.3 microns thick, granular and fibrillar ground substance
      which also extended into the cyst interior as thin septa. The membrane was folded
      and lined irregularly spaced, 0.8 to 1.3 microns tall villi centrally containing
      ground substance. The membrane was continuous in the villar projections, but
      divided into discrete aggregations of the electron dense material between the
      villi. Bradyzoites within the interior of the cyst were 3 by 12 microns. The
      sarcocysts were determined to be Sarcocystis felis based on the characteristic
      ultrastructural appearance of the cyst wall.

PMID- 9577780
TI  - Evaluation of a multivalent Pasteurella haemolytica vaccine in bighorn sheep:
      protection from experimental challenge.
AB  - The efficacy of a multivalent Pasteurella haemolytica vaccine (A1, A2, T10) in
      reducing morbidity and mortality associated with pneumonic pasteurellosis in
      bighorn sheep (Ovis canadensis) was examined. Fifteen captive bighorns were
      divided equally into three treatment groups based on vaccination status: control
      (no vaccination), one dose 10 days prior to challenge, or one or two doses 57 wk
      prior to challenge. At challenge, each bighorn received about 6.2 x 10(7) colony
      forming units of P. haemolytica (biotype T, serotype 10, biogroup 4-CDS; ribotype
      ECO; "Alamosa Canyon" strain) suspension sprayed into the proximal trachea.
      Vaccination reduced (P = 0.1) mortality in bighorns vaccinated 10 days prior to
      challenge as compared to controls. Although mortality rates in bighorns
      vaccinated 57 wk prior to challenge did not differ from controls (P = 0.26), a
      trend in reduced mortality was apparent. Ranked cumulative postmortem scores
      based on observed gross lesions and bacteriology did not differ (P > or = 0.14)
      between vaccinated animals and control animals. Neutralizing antibody titers to
      P. haemolytica leukotoxin were elevated (P = 0.003) at challenge in bighorns
      vaccinated 10 days before challenge, and neutralizing titers in bighorns from
      both vaccinated groups were elevated at death < or = 7 days after challenge (P <
      or = 0.004). In contrast, agglutinating antibody titers to P. haemolytica
      serotype A1 or T10 surface antigens did not differ between vaccinated and
      unvaccinated bighorns (P > or = 0.19). Based on these data, we believe that this
      experimental P. haemolytica vaccine is safe and can stimulate protective immunity
      from pneumonic pasteurellosis in bighorn sheep. Further evaluation of this
      vaccine as a tool in preventing and managing pasteurellosis in wild bighorn sheep
      appears warranted.

PMID- 9577781
TI  - Meningeal worm evokes a heterogeneous immune response in elk.
AB  - Meningeal worm (Parelaphostrongylus tenuis) is a neurotropic nematode of
      ungulates in eastern North America. Lack of an effective diagnostic test
      increases the concern of translocating potentially infected ungulates into
      western North America, where P. tenuis does not occur naturally. In an attempt to
      identify serodiagnostic molecules, we determined (1) whether elk (Cervus elaphus)
      experimentally infected with P. tenuis produce antibodies against infective
      larvae or adult worms, and (2) if sera consistently recognize antigens that
      distinguish P. tenuis from a common nematode parasite of elk, the lungworm
      Dictyocaulus viviparus. Each of 10 elk were exposed to 15 or 300 infective P.
      tenuis larvae. Serum was collected (0, 41, and 83 days post-exposure and at
      necropsy) and monitored for antibodies using the enzyme-linked immunosorbent
      assay (ELISA) and immunoblot. When reactivity of sera with larval P. tenuis
      protein was compared (day 0 versus 83), ELISA values were significantly higher on
      day 83 for elk exposed to 15 or 300 parasites. Likewise, ELISA values using
      protein of adult P. tenuis were higher for elk exposed to 300 larvae. Immunoblots
      showed that sera from elk, with adult worms in the central nervous system,
      consistently recognized the 25-27, 28-30, and 34-36 kDa antigens of infective
      larvae after 83 days. However, many D. viviparus molecules were found to cross
      react with antibodies formed against meningeal worm antigens. Use of adult worm
      proteins for serodiagnosis appears limited, because no protein was consistently
      recognized by sera collected from elk exposed to 15 larvae. We believe that
      development of a reliable diagnostic test for meningeal worm requires more
      research addressing cross-reactivity and detection of P. tenuis during the
      incubation stage.

PMID- 9577782
TI  - Immobilization of mountain goats with xylazine and reversal with idazoxan.
AB  - Mountain goats (Oreamnos americanus) were captured in traps and immobilized with
      xylazine, later reversed with idazoxan. One hundred and forty-one goats were
      immobilized, 94 with a single injection and 47 with multiple injections. Dosage
      (mg/kg of body weight) of xylazine received, induction time, and recovery time
      after handling did not differ among sex-age classes. Increasing the dosage did
      not shorten induction time. The first injection of xylazine in multiple-injection
      captures was lower than the dose given in single-injection captures, suggesting
      that insufficient initial doses of xylazine made multiple injections necessary.
      Xylazine is an effective drug for immobilization of mountain goats captured in
      traps, at dosages of about 4.9 mg/kg. The dosage of xylazine required to
      immobilize mountain goats is higher than that reported for bighorn sheep and
      white-tailed deer.

PMID- 9577783
TI  - Northern bobwhites as disease indicators for the endangered Attwater's prairie
      chicken.
AB  - Because of limited access to the endangered Attwater's prairie chicken
      (Tympanuchus cupido attwateri), we used a related species, the northern bobwhite
      (Colinus virginianus), as a surrogate for disease evaluation. Free-living
      northern bobwhites (n = 62) on the Attwater Prairie Chicken National Wildlife
      Refuge (near Eagle Lake, Texas, USA) were examined during spring and fall 1993
      for helminthic endoparasites and specific antibodies against the infectious
      agents responsible for nine infectious diseases. Trichostrongylus cramae,
      Raillietina sp., and Strongyloides avium were collected from 97, 44, and 32% of
      northern bobwhites examined, respectively. Dispharynx nasuta and Syngamus trachea
      also were found. No gross lesions due to parasites were observed. Specific
      antibody to Pasteurella multocida was found in 3 of 53 plasma samples. It is
      possible that potentially pathogenic species such as P. multocida, T. cramae, and
      D. nasuta could threaten sympatric Attwater's prairie chickens.

PMID- 9577784
TI  - Lyssaviral infection and lead poisoning in black flying foxes from Queensland.
AB  - Pteropid lyssaviral infection, lead poisoning, and the difficulties in diagnosing
      pteropid lyssaviral infection using histopathological examination of tissues are
      described in wild black flying foxes (Pteropus alecto) from northern Queensland
      (Australia). An adult female P. alecto showed aggression before death in January
      1995. Lead poisoning was diagnosed due to the presence of intranuclear lead
      inclusion bodies in renal proximal convoluted tubular epithelium and high
      concentrations of lead in renal and hepatic tissues, 370.03 +/- 7.35 ppm and
      16.76 +/- 0.53 ppm, respectively. Renal inclusion bodies were composed of lead,
      calcium, phosphorus, and possibly sulphur; some inclusions had their granules
      arranged in concentric bands. This bat also had a moderate concentration (8.09 +/
      0.18 ppm) of cadmium in renal tissue. An adult male P. alecto presented with
      ascending paralysis before it died in May 1996. Pteropid lyssaviral infection was
      diagnosed subsequently in both bats in September 1996 by immunofluorescent and
      immunoperoxidase antibody tests for rabies on brains and viral culture from
      brains. Neither bat had gross or microscopic lesions of the brain that suggested
      a lyssaviral infection, apart from occasional, subtle, eosinophilic cytoplasmic
      inclusions in the neurones of the brain stem of the female. These cases
      illustrate the need for a specific test to detect pteropid lyssavirus such as an
      immunofluorescent antibody test for lyssavirus rather than histopathological
      examination of tissues.

PMID- 9577785
TI  - Lack of relay toxicity in ferret hybrids fed carbaryl-treated prairie dogs.
AB  - Carbaryl (1-napthol methylcarbamate) is being considered for control of fleas on
      prairie dogs (Cynomys spp.) used in black-footed ferret (Mustela nigripes)
      recovery in the western United States. The potential for relay toxicity in
      ferrets was determined by feeding carbaryl treated prairie dogs to black-footed
      ferret x Siberian polecat (M. eversmanni) hybrids. Adult prairie dogs were
      treated topically with 2.5 g of commercial 5% carbaryl dust sold as flea powder.
      After 14 days prairie dogs were killed and fed to ferrets. Potential for relay
      toxicity was evaluated by analyzing ferret blood cholinesterase (CHe), prairie
      dog brain Che, and hepatic carbamate concentration. There was no difference
      between pre- and post-exposure blood CHe activity, nor did treated prairie dog
      brain CHe differ significantly from controls. Post-exposure blood CHe did not
      exhibit reactivation after dilution in aqueous buffer. Hepatic carbaryl
      concentrations were less than detection limits (50 ppb). Based on these results,
      we conclude that short-term use of carbaryl for flea control on prairie dogs does
      not pose a hazard of relay toxicity in black-footed ferrets.

PMID- 9577786
TI  - Surgical plating of a fractured radius and ulna in a wild Canada lynx.
AB  - A free-ranging, adult male Canada-lynx (Lynx canadensis) experienced a closed,
      complete, non-comminuted transverse fracture of the left radius and ulna when
      captured in a leg snare. A dynamic compression plate (DCP) attached to the
      anterior surface of the radius was used to stabilize the fracture. Radiographs 44
      days post-surgery indicated advanced primary bone healing. The lynx was released
      46 days post-surgery near the site of capture. Radiotelemetry indicated long-term
      survival and movements similar to other males monitored during the same period.

PMID- 9577787
TI  - Evaluation of two oral baiting systems for wild rodents.
AB  - Tetracycline hydrochloride (TC)-treated peanut butter or rodent chow baits were
      distributed during March 1990, on separate 0.53 ha sites in Oglethorpe County,
      Georgia (USA). Rodents were trapped on a control site prior to bait distribution
      and on two baited sites 6 days post-distribution. Cleaned skulls from euthanized
      mammals were grossly examined for TC fluorescence using an ultraviolet (UV)
      light. Mandibles were sectioned and examined for TC fluorescence using an
      ultraviolet light microscope. All 21 cotton rats (Sigmodon hispidus), four
      eastern harvest mice (Rithrodontomys humulis), and two golden mice (Ochrotomys
      nuttalli) captured on the control site were negative for TC fluorescence. On the
      peanut butter bait site, mandible sections from 29 of 32 (91%) cotton rats, three
      of three (100%) eastern harvest mice, two of three (66%) golden mice, zero of
      five (0%) white-footed mice (Peromyscus leucopus), one of three (33%) short
      tailed shrews (Blarina brevicauda), and zero of two (0%) least shrews (Cryptotis
      parva) were positive for TC. Results from the rodent chow bait site indicated
      that 18 of 25 (72%) cotton rats, zero of three (0%) eastern harvest mice, two of
      seven (29%) golden mice, zero of four (0%) white-footed mice, and zero of four
      (0%) least shrews were positive for TC fluorescence in mandible sections. These
      results suggest that a large portion of a free-ranging small rodent population
      can be administered biological markers or vaccines using baits.

PMID- 9577788
TI  - Uterine adenocarcinoma with abdominal carcinomatosis in a beluga whale.
AB  - A case of uterine adenocarcinoma is reported in a 26-yr-old, free-ranging beluga
      whale (Delphinapterus leucas) from the St. Lawrence estuary (Quebec, Canada).
      This neoplasm appeared as a segmental stenotic thickening of the left uterine
      horn composed of well differentiated, but disorganized and infiltrative,
      glandular structures surrounded by an extensive scirrhous stroma. Abdominal
      carcinomatosis was observed on the mesosalpinx and on the serosal aspect of the
      gastric compartments. This is the first report of a malignancy originating in the
      uterus of a cetacean.

PMID- 9577789
TI  - Intestinal plasmacytoma in an African hedgehog.
AB  - A 3-yr-old male African hedgehog (Atelerix albiventris) had anorexia and weight
      loss for 1 wk before its death. The colon and mesocolon were diffusely
      infiltrated by a neoplastic proliferation of round cells with plasmacytoid
      features. A diagnosis of intestinal plasmacytoma was made and confirmed by
      electron microscopy. No other organs appeared to be affected. This is the first
      description of intestinal plasmacytoma in a hedgehog.

PMID- 9577790
TI  - Effect of season on oral and gastric nematodes in the frillneck lizard from
      Australia.
AB  - The prevalence and intensity of nematodes from the stomach and the prevalence of
      nematodes in the oral cavity were recorded in the frillneck lizard,
      Chlamydosaurus kingii, in Kakadu National Park (Australia) between 1991 and 1994,
      in order to determine whether or not a seasonal pattern was evident. Seven
      species were recorded; Strongyluris paronai, Skrjabinopatera goldmanae,
      Abbreviata confusa, Abbreviata anomala, Physalopteroides filicauda, Kreisiella
      sp. and a species of Trichostrongyloidea. Only S. paronai showed a seasonal
      pattern. Only larval S. paronai occurred in stomach samples and larvae of this
      species occurred seasonally in the oral cavity of C. kingii, substantiating
      earlier findings that this genus migrates within the host. The occurrence of S.
      paronai in the oral cavity coincided with the highest prevalence and intensity of
      S. paronai in stomach samples. This shows a previously unrecorded aspect in the
      life cycle of this nematode species. Prevalence of S. paronai was positively
      correlated with ambient temperature which is highest in the months preceding the
      monsoonal rains, and coincides with an increase in field metabolic rate and
      general activity of the host.

PMID- 9577791
TI  - Increasing prevalence of canine heartworm in coyotes from California.
AB  - Thirty-seven subadult and adult coyotes (Canis latrans), collected August 1992
      through December 1996 from a coastal foothill area in northern California (USA),
      were examined for adult heartworm (Dirofilaria immitis). During 1992 through
      1993, at the end of a 6 yr drought, none of four coyotes examined were infected
      with heartworms. However, during 1994 through 1996, after the drought had ended,
      prevalences were 91% in 23 adult coyotes and 40% in 10 subadult coyotes.
      Heartworm intensity did not differ by sex of coyote, and averaged (+/- SE) 19.4
      +/- 3.8 among adults; one subadult had > 238 heartworms. The prevalence and
      intensity of heartworm infection in coyotes reported here for 1994 through 1996
      are the highest reported anywhere in the United States.

PMID- 9577792
TI  - Dispharynxiasis in a captive princess parrot.
AB  - The acuariid nematode Dispharynx nasuta was found in a princess parrot, Polytelis
      alexandrae, at the National Aviary in Pittsburgh (Pennsylvania, USA). This is the
      first report of D. nasuta from the host order Psittaciformes, and was the
      presumed cause of death in this parrot.

PMID- 9577793
TI  - Lack of seroreactivity to Ehrlichia chaffeensis among rodent populations.
AB  - A retrospective serosurvey for antibodies to Ehrlichia chaffeensis was conducted
      on eight species of wild rodents (Mus musculus, Oryzomys palustris, Peromyscus
      leucopus, Rattus norvegicus, Reithrodontomys humulis, Sciurus carolinensis,
      Sciurus niger, and Sigmodon hispidus) from the southeastern United States. Serum
      samples (n = 281) collected between 1973 and 1993 were evaluated using an
      indirect fluorescent antibody test. All samples, screened at a dilution of 1:32,
      were negative for antibodies to E. chaffeensis. Sixty-three percent of the
      rodents tested were from areas where E. chaffeensis has been confirmed or is
      strongly suspected to be endemic. These data suggest limited or no involvement of
      rodents in the epidemiology of E. chaffeensis.

PMID- 9577794
TI  - Corynebacterial pneumonia in an African hedgehog.
AB  - A 3-mo-old, male African hedgehog (Atelerix albiventris) was anorectic and
      lethargic for a period of 3 days prior to death. Necropys revealed lungs that
      were diffusely firm, dark red, and dorsally adhered by fibrinous tags to the
      pericardial sac. Histopathology revealed necrosuppurative bronchopneumonia with
      pulmonary abscesses and suppurative pericarditis and myocarditis. A
      Corynebacterium sp. was isolated from the lungs. We believe this is the first
      reported case of corynebacterial pneumonia in an African hedgehog.

PMID- 9577795
TI  - Isolation of Brucella melitensis from alpine ibex.
AB  - Eleven alpine ibex (Capra ibex) and 27 chamois (Rupicapra rupicapra) from Gran
      Paradiso National Park (Italy) were examined in March 1996. A 7-yr-old ibex buck
      had thick-walled carpal joints and enlargement of the right testicle
      characterized by necrosis and fibrosis. Microscopically, testicular lesions were
      characterized by large areas of necrosis, fibrosis with irregular aggregates of
      macrophages and lymphocytes, and scattered foci of suppuration. Specimens of the
      carpal bursae and testicle were cultured in serum dextrose agar and serum
      dextrose antibiotic plates. A Gram-negative coccobacillus was isolated from the
      testicle and subsequently identified as Brucella melitensis biotype 2. This is
      the first recognized case of brucellosis in alpine ibex.

PMID- 9577796
TI  - Mycoplasma sturni from blue jays and northern mockingbirds with conjunctivitis in
      Florida.
AB  - Northern mockingbirds (Mimus polyglottos) and blue jays (Cyanocitta cristata) in
      a Florida (USA) wildlife care facility developed clinical signs and gross lesions
      suggestive of the ongoing outbreak of Mycoplasma gallisepticum (MG)
      conjunctivitis in house finches (Carpodacus mexicanus) and American goldfinches
      (Carduelis tristis). Mycoplasmal organisms were cultured from
      conjunctival/corneal swabs of birds with sinusitis, conjunctivitis, and/or
      epiphora. All of the isolates tested were identified as Mycoplasma sturni by
      indirect immunofluorescence. Mycoplasma sturni as well as MG should be considered
      in the differential diagnosis of songbirds with conjunctivitis.

PMID- 9577797
TI  - Leptospirosis in rehabilitated Pacific harbor seals from California.
AB  - Renal disease was observed in two rehabilitated Pacific harbor seals (Phoca
      vitulina richardsii) from a facility in California (USA). The seals had
      leukocytosis and high serum phosphorus, blood urea nitrogen and creatinine
      concentrations. A retrospective study of leptospiral antibody serum titers
      indicated both seals had elevated titers to Leptospira interrogans serovar
      grippotyphosa. A third seal, which died about the time when the index cases
      occurred, also had elevated titers to L. interrogans serovar grippotyphosa. Post
      mortem histopathologic examination of all three seals showed tubular necrosis
      consistent with interstitial nephritis; spirochetes were seen within the kidney
      parenchyma of the third seal. Sea lions (Zalophus californianus) or elephant
      seals (Mirounga angustirostris) housed near the harbor seals were possible
      sources of exposure, but local wildlife also could have been responsible.

PMID- 9577798
TI  - Serologic survey for antibodies to Borrelia burgdorferi in white-tailed deer in
      Ontario.
AB  - Serum samples collected from 623 white-tailed deer (Odocoileus virginianus) in
      southern Ontario (Canada) from 1985 to 1989 were tested for antibodies to
      Borrelia burgdorferi using an indirect fluorescent antibody (IFA) staining
      method. Samples from 150 of the deer were also tested using an enzyme-linked
      immunosorbent assay (ELISA). At IFA titers of 1:64 and 1:128 deer with antibodies
      to B. burgdorferi appeared to be widespread throughout southern Ontario, with an
      apparent prevalence ranging from 3 to 47%. At IFA titres > or = 1:256 and ELISA
      titres > or = 1:160 deer with antibodies to B. burgdorferi were only present on
      Long Point which is the only known endemic focus of Ixodes scapularis, the
      primary vector for B. burgdorferi, in southern Ontario. At these titres the
      apparent prevalence of antibodies to B. burgdorferi on Long Point was only 5 to
      7%, even though the mean intensity of infestation of adult I. scapularis on deer
      was > 180, and 60% of the adult ticks are infected with B. burgdorferi. Based on
      these results, white-tailed deer do not appear to be a good sentinel species for
      the distribution of B. burgdorferi.

PMID- 9577801
TI  - [How well do sunglasses protect from damaging UV rays?].

PMID- 9577799
TI  - Concerning treatment of fascioloidiasis.

PMID- 9577803
TI  - [Development of perimetry since antiquity].
AB  - Even in greeque medicine the visual field has been described and recognized.
      Besides the visual acuity, references are given on early observations of the
      visual field and its defects. Ptolemaeus (87-165 n. Chr.) first mentioned a
      method to test the visual field and also gave some physical definitions. Further
      developments are described in detail. From this oldest method it was a long way
      to develop techniques for measurement and quantification which could be used in
      clinical practice. There was an amazing high number of different inventions and
      parallel developments of methods testing the visual field in the last century.

PMID- 9577804
TI  - [Can the extent of glaucoma damage be assessed by measuring the asymmetry of the
      peripapillary height profile between the upper and lower retinal half? A clinical
      study with the Heidelberg Retina Tomograph].
AB  - BACKGROUND: Peripapillary height measurements are possible using 2 different
      reference planes of the Heidelberg-Retina-Tomograph. It is not tested yet,
      whether the extent of glaucoma damage should be better quantified using reference
      plane 1 or 2. PATIENTS AND METHODS: In 32 eyes of 32 glaucoma patients with a
      defined up-down asymmetry of visual field loss is tested I.) if there is a
      significant correlation between peripapillary height and visual field loss
      comparing reference plane 1 and 2. II.) if there is a conformable up-down
      asymmetry of the peripapillary height using a new "retinal-asymmetry-difference"
      (RAD). III.) if conformity between peripapillary height and visual field loss
      depends on the distance from the disc margin. RESULTS: 1.) For an advanced visual
      field loss there was a significant correlation between visual field loss and
      peripapillary height using reference plane 1. II.) In eyes with a big up-down
      asymmetry of visual field loss there was a bigger conformity between the up-down
      asymmetry of visual field loss and the up-down asymmetry of peripapillary height
      (11 of 12 eyes), as for a small up-down asymmetry (12 of 20 eyes). III.)
      Conformity decreases with the distance from the disc margin. CONCLUSIONS:
      Peripapillary height should be examined using measurement circles near the disc
      margin. Because of its independence on the age and on different reference planes
      additional calculation of an up-down "retinal-asymmetry-difference" (RAD) seems
      to be useful. Using this up-down "retinal-asymmetry-difference" (RAD) a big up
      down asymmetry of visual field loss, equivalent to an advanced glaucomatous
      disease, is quantified with high sensitivity.

PMID- 9577805
TI  - [Flare measurement and albuminuria in type I diabetics].
AB  - BACKGROUND: Chronic hyperglycaemia causes microangiopathy with manifestations in
      different organ systems. The purpose of this study was to investigate whether
      anterior chamber protein concentrations and albuminuria in patients with diabetes
      mellitus type 1 have any correlation. PATIENTS AND METHODS: 23 patients with type
      1 diabetes were examined in both eyes by the use of the laser flare-cell meter
      (LFCM). After clinical exclusion of urinary tract infection urine-samples were
      taken on the examination-day. Patients were divided into two groups: group 1
      consisted of 13 patients with albuminuria (8x microalbuminuria, 5x
      macroalbuminuria), group 2 comprised 10 controls with normal urine albumin
      concentrations. RESULTS: Both groups were identical according to age and gender.
      The flare values in the group with albuminuria were significantly elevated (10.7
      +/- 7.1 counts/msec) in comparison to those of the control group (3.7 +/- 1.9
      counts/msec)(p = 0.042). The duration of the diabetes was as well significantly
      different in both groups (7.9 +/- 6.9 yrs. vs. 23.9 +/- 13.4 yrs.)(p = 0.02). A
      correlation was found between albuminuria and flare values (r = 0.67; p = 0.003).
      CONCLUSIONS: Our results demonstrate a correlation between protein concentration
      in aqueous and albuminuria. In future flare measurements could possibly offer a
      non-invasive diagnosis of diabetic nephropathy.

PMID- 9577806
TI  - [Toxoplasmosis retinochorioiditis, a therapy comparison between spiramycin and
      pyrimethamine/sulfadiazine].
AB  - BACKGROUND: The treatment of toxoplasma retinochoroiditis with spiramycin is an
      alternative to sulfadiazine and pyrimethamine. The treatment with sulfadiazine is
      associated with multiple side effects. Sulfadiazine is contraindicated during
      pregnancy and breastfeeding period. Spiramycin has less side effects and is
      recommended during pregnancy and breastfeeding period. The efficacy of spiramycin
      in treatment of toxoplasma retinochoroiditis is still a matter of controversy.
      PATIENTS AND METHODS: In a retrospective study, side effects and outcome of
      therapy in 44 patients with toxoplasma retinochoroiditis treated with
      sulfadiazine and pyrimethamine (n = 30) or spiramycin (n = 14) were compared. We
      assessed duration of therapy and healing, ophthalmoscopic findings and observed
      side effects. RESULTS: The mean healing time in the group of spiramycin was 63.83
      days in comparison to 88 days for the group of patients treated with
      sulfadiazine/pyrimethamine. The frequency of side effects was lower in the group
      treated with spiramycin. CONCLUSION: In comparison to a combined application of
      sulfadiazine and pyrimethamine the treatment with spiramycin alone requires a
      shorter duration of therapy and healing period. Additionally, side effects and
      contraindications appear to be less frequent. In view of these findings,
      spiramycin therapy must be considered as a promising approach in the treatment of
      toxoplasma retinochoroiditis.

PMID- 9577807
TI  - [Multi-flash ERG in cone dystrophies and cone-rod dystrophies].
AB  - BACKGROUND: Scotopic electroretinograms elicited with a multiple flash procedure
      were reported to be helpful in diagnosis of macular diseases. To evaluate the
      contribution of rods and cones to the recovery of light responses as recorded
      with this technique we performed a triple flash ERG procedure in patients with
      cone dystrophies and cone-rod dystrophies. MATERIALS AND METHODS: In 8 patients
      with cone dystrophy and 8 patients with cone-rod dystrophy and also in 18 healthy
      controls we recorded a standard ERG and the scotopic triple flash ERG with
      intensities between 0.01 and 0.2 cds/m2. Interflash intervals were adjusted at
      140, 280, and 560 ms. Responses of the standard ERG were analysed as well as b
      wave amplitudes at the short dark interval (140 ms) and the longer dark interval
      (280 ms). These responses were compared to responses after a long interflash
      interval (560 ms). Using a theoretical model parameters of b-wave recovery were
      determined and compared between the groups. RESULTS: In cone dystrophies
      responses of the scotopic triple flash ERG and the b-wave recovery parameters
      were normal whereas in combined dystrophies the triple flash responses were
      abnormal and the recovery data were pathologic. CONCLUSIONS: Cones did neither
      contribute to responses obtained with the multiple flash technique nor did they
      affect b-wave recovery as tested with this technique. Pathologic responses as
      described earlier with this technique in macular diseases could only be
      attributed to pathomechanisms globally affecting the rod system, e.g. dysfunction
      of retinal energy metabolism.

PMID- 9577808
TI  - [Multifocal electroretinography in acquired macular dysfunction].
AB  - BACKGROUND: Multifocal electroretinography allows physiological mapping of the
      central retina. The purpose of this study was to describe the spatial
      distribution of ERG-activity in patients with impairment of macular function
      which usually do not exhibit a pathologic Ganzfeld-ERG. SUBJECTS AND METHODS: 6
      patients with macular lesions due to uveitis (4), retinitis centralis serosa (1),
      and contusio bulbi (1) were examined using the multifocal ERG technique. RESULTS:
      In normal volunteers the response density of the multifocal ERG decreased with
      eccentricity according to cone density distribution. In eyes with impaired
      central vision the foveal and macular responses were markedly diminished while
      surrounding signals were of normal or moderately decreased amplitudes.
      CONCLUSIONS: With the multifocal ERG disturbances of macular function due to
      oedema and secondary structural changes were detected in the presented cases and
      the extension of the central lesions was estimated.

PMID- 9577809
TI  - [Evaluation of the filtering bleb using ultrasound biomicroscopy].
AB  - BACKGROUND: Sometimes in glaucomatous patients treated with trabeculectomy there
      is not a correlation between bleb shape and intraocular pressure. So we studied
      the functional anatomy of the filtering bleb by a ultrasound biomicroscope, using
      high frequency (50 Mhz) probe, which provides high resolution images of filtering
      blebs. MATERIALS AND METHODS: A total of 46 filtering blebs of 46 patients after
      trabeculectomy were analyzed by ultrasound biomicroscopy (50 Mhz). Dimensions,
      shapes and structure of blebs were evaluated in 2 groups of patients. RESULTS: It
      was possible to obtain longitudinal or transverse images of filtering blebs, to
      measure the height, to evaluate the reflectivity inside and to follow the route
      under the scleral flap. Blebs with lower reflectivity and a visible route under
      the scleral flap had a lower intraocular pressure while the height was not
      important for a good intraocular pressure. CONCLUSIONS: So ultrasound
      biomicroscopy can be a useful method to study filtering blebs and also to explain
      the mechanisms of filtering structures in patients who underwent trabeculectomy.

PMID- 9577810
TI  - [Driving behavior of patients before cataract operation--is an unlimited driver's
      license justifiable? Results of an analysis of 1,124 patients of the
      ophthalmology department of a central hospital].
AB  - BACKGROUND: The aim of the study was to evaluate the driving habits and patterns
      of those patients, who underwent cataract-surgery during a one year period at the
      Landesaugenklinik Salzburg and to compare the preoperative visual acuity with the
      legal requirements in effect in Austria. MATERIALS AND METHODS: The best
      corrected visual acuity prior to surgery and the individual driving customs were
      noted on a detailed questionnaire. RESULTS: A minimum of 5.6% of the overall
      number of patients with cataract (not taking visual field defects into account)
      were driving a motor vehicle with a visual acuity not sufficient to meet current
      legal requirements. Considering only those drivers licence holders that admitted
      to still driving a motor vehicle it can be concluded that 26% have a legally
      unsatisfactory visual acuity. As between 28,000 and 31,000 cataract-operations
      are performed yearly in Austria, this study seems to clearly indicate that at
      least 1,600 of these persons--regardless of an additional visual field defect-
      are illegally driving a motor vehicle. It can be additionally concluded that the
      number of undetected cases is significantly higher. CONCLUSIONS: It therefore
      seems appropriate to call for a mandatory eye exam by a qualified ophthalmologist
      of all persons holding a driving licence, possibly beginning at the age of 60.
      The license issued thereafter should be valid for an age-related period of time
      only.

PMID- 9577811
TI  - [Teleconsultation network for ophthalmology--experiences and results].
AB  - MOTIVATION: Telemedical services for ophthalmology are developed within the
      OPHTEL project, which has been funded by the European Union and by the Bavarian
      government in the Bavaria-online initiative. METHODS: Seven private
      ophthalmologists, one university eye clinic, one clinical Diabetes center and an
      informatics research institute are connected within a teleconsultation network.
      Asynchronous (based on Internet E-Mail) and synchronous (based on ISDN-mediated
      videoconferencing tools) types of teleconsultations are realized. RESULTS: 86
      teleconsultations (62 asynchronous, 23 synchronous) took place within the first
      10 months. Complex and rare eye diseases as well as interdisciplinary questions
      (ophthalmology--diabetology) are the main area of medical communication interest.
      Legal and security problems are discussed. CONCLUSIONS: Telemedical services must
      be understood as a complete process of medical care on the basis of modern
      communication technologies, which influences also the management of this process.

PMID- 9577812
TI  - [Progressive disseminated essential telangiectasia with conjunctival
      involvement].
AB  - BACKGROUND: Widespread idiopathic telangiectasia (generalized essential
      telangiectasia) is a rare skin disorder characterized by the development and
      gradual spreading of telangiectases. The condition tends to affect women in their
      midthirties. For no apparent reason telangiectases start to appear to the lower
      extremities and progress steadily to involve the skin of the trunk, the arms, and
      the face. General health is not affected by the condition and standard laboratory
      tests consistently yield normal results. CASE REPORT: In February 1997 a 78-year
      old lady was admitted for treatment of cataracta corticonuclearis of her left
      eye. Complete ophthalmological and dermatological examinations were performed.
      She presented marked conjunctival telangiectases of both eyes and widespread
      cutaneous telangiectases involving her face, trunk, arms, and legs. Complete
      blanching of lesional skin was observed on diascopy. The Rumpel-Leede-test was
      normal. Cutaneous and conjunctival changes appeared not to be associated with
      internal disease or bleeding abnormalities. DISCUSSION: The patient presented
      here shows widespread idiopathic telangiectasia with marked conjunctival
      involvement. Ocular changes rarely have been reported in patients with
      generalized essential telangiectasia to date. Concomittant conjunctival and
      cutaneous telangiectases may be seen in other conditions such as hereditary
      hemorrhagic telangiectasia (Rendu-Osler-Weber disease) and ataxia telangiectasia
      (Louis-Bar syndrome). The former shows an associated bleeding abnormality and is
      transmitted autosomal dominantly. The latter presents associated neurological
      signs such as cerebellar ataxia, strabism, nystagmus, apraxia, and mental
      retardation.

PMID- 9577813
TI  - [Bilateral endogenous endophthalmitis].
AB  - BACKGROUND: The endogenous endophthalmitis is a septic-metastatic late
      complication of a generalized bacterial or fungal infection or an asymptomatic
      fungaemia. Aspergillus organisms are a rare cause of endophthalmitis. Aspergillus
      ocular manifestations have been mostly reported in connection with
      immunosuppression, severe diseases or drug abuse. PATIENT AND METHODS: A 51-year
      old man underwent a kidney transplantation, an immunosuppressive therapy, and, in
      addition, treatments for some other generalized diseases. Endogenous
      endophthalmitis was diagnosed in both eyes at an interval of about eight weeks.
      The treatment included pars-plana-vitrectomy on both eyes. RESULTS: At first, an
      endogenous endophthalmitis was found in the right eye which was assumed to be
      induced by bacteria. About eight weeks later, however, an endogenous
      endophthalmitis was diagnosed in the left eye, also, which was caused by
      Aspergillus. The patient received an intensive medical care including operative,
      antibacterial and antimycotic treatments. The bacterial endophthalmitis in the
      right eye was healed, and the state of the left eye was found to be post
      operatively stabilized. Unfortunately, the patient died of a septic shock in
      systemic Aspergillus infection. CONCLUSION: Endogenous endophthalmitis has a very
      poor prognosis. To our knowledge, the described medical history seems to be the
      first reported case of an endophthalmitis on both sides, apparently caused by
      bacteria in one eye and by fungi in the other one.

PMID- 9577814
TI  - [Molluscum contagiosum in immunosuppression with methotrexate: multiple warts
      with central depressions of the eyelids].
AB  - BACKGROUND: Poxvirus induced molluscum contagiosum is known to occur in children,
      elderly people and in patients with the acquired immune deficiency syndrome AIDS.
      PATIENT AND METHODS: We report on a 49-year-old patient who presented with a
      three-month history of multiple skin-coloured prominent warts on his right upper
      and lower eye-lid. On examination, the warts showed a central cavity and measured
      2-6 mm in diameter. For his "mixed connective tissue disease" (MCTD) the patient
      took methotrexate in a weekly dosage of 7.5 mg since 3 years. Diagnosis of MCTD
      was made 7 years before. The warts were excised and studied histopathologically.
      One year postoperatively, there was no recurrence of the lesions. CONCLUSION:
      Drug induced immunosuppression as with methotrexate may be associated with
      multiple periocular lesions due to molluscum contagiosum.

PMID- 9577815
TI  - [Atypical non-Hodgkin's lymphoma of the conjunctiva as an incidental finding in
      lower lid entropion].
AB  - PURPOSE: We want to demonstrate an unusual conjunctival Non-Hodgkin-Lymphoma with
      bleedings. PATIENT: A 77-year-old female patient presented with an entropion of
      the left lower eye-lid. Bilaterally reddish, soft tumors showed in the lower
      fornices with circumscript bleedings. On account of an absolute arrhythmia of the
      heart the patient has been on a medication of cumarine-derivates since 9 years.
      Histologically we found underneath the epithelium densely packed lymphocytic
      cells with small uniform nuclei intermingled with many erythrocytes. The
      immunohistological investigations revealed a Non-Hodgkin-Lymphoma of B-cell
      origin. CONCLUSIONS: Bleedings in a conjunctival Non-Hodgkin-Lymphoma can alter
      the clinical aspect of the tumor. It is necessary to inspect each entropion
      thoroughly in order to rule out any other pathological lesions.

PMID- 9577816
TI  - [Epithelial giant inclusion cyst 50 years after enucleation without orbital
      implant].
AB  - BACKGROUND: Conjunctival cyst formation following enucleation may occur in 3% to
      7% of patients receiving orbital implants, especially secondary implants. We
      present a patient with a giant epithelial inclusion cyst of the anophthalmic
      orbit 50 years after enucleation without orbital implant. PATIENT: A 54-year-old
      male presented with increasing proptosis of the ocular prosthesis, shallowing of
      the inferior fornix, a palpable orbital mass, and difficulty in retaining the
      ocular prosthesis. At the age of 1 year enucleation of the right eye without
      orbital implant was performed following perforating ocular trauma. Results of
      examination of the other eye were unremarkable. Transillumination of the orbital
      mass was possible. The clinical diagnosis of an epithelial inclusion cyst was
      confirmed using ultrasonography and CT scan. An incision of conjunctiva and cyst
      wall and subsequent marsupialization were performed. Nine months postoperatively
      there was no evidence of recurrence of the cyst. The ocular prosthesis was well
      in place. CONCLUSION: Conjunctival cyst formation following enucleation may
      rarely occur in patients receiving orbital implants, especially secondary
      implants. The presentation of a conjunctival cyst formation following enucleation
      without orbital implant 50 years after surgery is noteworthy in comparison to
      implantation cysts which are known to occur more commonly within the first two
      years following secondary orbital implants.

PMID- 9577817
TI  - [Early detection of profound hearing loss in children. Results of screening
      students in Rhine schools for the deaf and hearing impaired in Cologne].
AB  - OBJECTIVE: Early detection and adequate and timely rehabilitation of profound
      deafness in children is accepted as an important aim of preventive child health
      care. Ideally, rehabilitation of congenital deafness should not be delayed beyond
      the age of six months. The present study seeks to determine whether this goal has
      been achieved in Germany in the 1990s. PATIENTS AND METHODS: The medical charts
      of 314 profoundly hearing impaired pupils at the schools for the hearing impaired
      in Cologne, Germany, were reviewed. All available data on the time of first
      suspicion and the final diagnosis were collected. In addition, the families of
      these children were interviewed using a standardized questionnaire. RESULTS: The
      mean age at first suspicion was 2.1 years, the mean age at the time of final
      diagnosis was 2.6 years (median: 2.0 years). Breaking down the whole cohort into
      three subgroups according to the year of birth revealed obvious differences
      between these subgroups. The final diagnosis for those born from 1974 to 1979 (n
      = 70) was confirmed in 48.6% at the age of two years, in 46.3% for those born
      from 1980 to 1985 (n = 121), and in 65.8% for those born from 1986 to 1991 (n =
      114) at the age of two. The diagnosis was significantly delayed for children of
      immigrants (n = 96), where the mean age at diagnosis was 3.7 years as opposed to
      2.0 years for the native German population. Of the 314 children, 304 where
      supplied with hearing aids and five with cochlear implants. Once the audiological
      diagnosis had been established, no further delay in rehabilitation was noticed.
      CONCLUSION: Although highly sensitive, cost effective, and non-invasive screening
      methods (transient evoked otoacoustic emissions and auditory brainstem response
      audiometry) for the early detection of profound inborn hearing impairment are now
      available, the current state of early identification of these disorders is
      inadequate. The reason for this is the lack of a universal and nationwide
      neonatal screening program. The results of this study indicate that the pure
      availability of sophisticated screening methods is insufficient if they are not
      included in a universal screening program.

PMID- 9577818
TI  - [An optimal electrode position for recording auditory evoked brain stem
      potentials within the scope of pediatric audiology].
AB  - BACKGROUND: Estimation of hearing threshold in children is based on reliable
      identification of a response to a stimulus in the near-threshold range. It is
      well known that only wave V can be detected in brainstem potentials evoked by
      near-threshold stimuli. So the question arises as to whether or not a noncephalic
      reference electrode compared to the common lateral postition of the reference
      electrode on the ipsilateral mastoid produces a more stable wave V of increased
      amplitude. METHOD: Thirty-three normal hearing children in three age groups (< 6
      years, 6-10 years, > 10 years) were investigated. For a near-threshold
      stimulation with 100-microsecond-clicks (10, 20, 30 dB nHL), bioactivity was
      simultaneously recorded with the reference electrode in four different locations
      (ipsilateral mastoid, contralateral mastoid, ipsilateral earlobe, and noncephalic
      electrode). RESULTS: The noncephalic reference produced the highest absolute and
      scaled amplitudes. This finding was statistically significant. For all
      investigated intensities, recording with the noncephalic reference electrode
      yielded the highest number of reliable detectable potentials. Evaluation of the
      residual noise in the four recording locations revealed a significantly increased
      noise level for the noncephalic electrode at the nape of the neck. CONCLUSIONS:
      Even if the residual noise is increased, the use of noncephalic reference results
      in a more reliable detection of wave V compared to the conventional locations of
      the reference electrode.

PMID- 9577820
TI  - [Experiences in diagnosis of occult traumatic dural lesions of the anterior
      cranial base].
AB  - BACKGROUND: Meningitis or cerebrospinal fluid rhinorrhea can occur years or even
      decades after trauma and can be the first indication of a previously unidentified
      dural lesion. In spite of being difficult, precise localization of an occult
      traumatic dural lesion is a necessary prerequisite for duraplasty. PATIENTS AND
      METHODS: In a retrospective study covering a period of 17 years, we identified 27
      patients with occult traumatic dural lesions. The dural lesions were localized by
      high-resolution CT, MRI, fluorescein nasal endoscopy, and CT cisternography. In
      all cases the expected dural lesion was demonstrated and treated surgically.
      RESULTS: In 23 out of 27 patients (85%), the rhinobasal fistula was detected as a
      bony defect by CT. Furthermore MRI examination in 100% (5/5), a preoperative
      fluorescein nasal endoscopy in 50% (10/20) and CT cisternography in 56% (5/9)
      were able to localize the dural lesion. CONCLUSION: We recommend high-resolution
      CT and MRI as diagnostic tools of choice in searching for occult dural lesions.
      Fluorescein nasal endoscopy and CT cisternography are justified as invasive
      techniques if CT and MRI are inconclusive but clinically CSF leakage is still
      suggested. The patient will remain at risk of potentially fatal meningitis until
      the lesion is appropriately repaired by duraplasty. Therefore modern clinical and
      radiological diagnostic methods should be used to search for an unknown dural
      lesion.

PMID- 9577819
TI  - [Cochlear implant for non-deaf patients?].
AB  - BACKGROUND: Cochlear implants have proven to be the method of choice for
      postlingually deafened adults. The great success of this application requires
      discussion of the degree in which the indication for cochlear implantation should
      be expanded to include patients with residual hearing. METHOD AND PATIENTS:
      Following an initial discussion of the term deafness, we present the preoperative
      and postoperative results in five patients with residual hearing. These patients
      achieve a certain degree of speech recognition with their well fitted hearing
      aids. However, their aided speech intelligibility did not exceed 30% with the
      standardized Freiburg monosyllabic word test at 70 dB. In each case the worse
      hearing ear was treated with a cochlear implant. Speech discrimination in silence
      and noise are compared with the results of a group of postlingually deafened
      cochlear implant patients. RESULTS: The five patients are very satisfied with the
      cochlear implant and use the telephone to communicate with unknown partners. They
      score 100% in the standardized four-syllable number test above 55 dB and they
      document a loss of speech discrimination between 0 and 25% within the open-set
      monosyllabic word test. The mean increase of best monosyllable intelligibility by
      the cochlear implant over the hearing aids is 65%. Using the innsbruck sentence
      test the patients score 100% at 70 dB; with the Gottingen sentence test, the mean
      result is 75%. Their mean results in noise are also very good, 76% at 10 dBS/N
      and 57% at 5 dBS/N respectively. None of these patients use the hearing aid on
      the untreated, better hearing ear. CONCLUSION: A multichannel cochlear implant
      lead to a significant improvement of speech comprehension in these patients with
      residual hearing. We can successfully implant patients with minimal benefit of
      their well fitted hearing aids. Our group is too small to be able to define
      general selection criteria. For the time being we use as an audiological
      indication a open-set monosyllabic word intelligibility of not more than 30% at
      70 dB with well fitted hearing aids.

PMID- 9577821
TI  - [Obstructive sleep apnea and obstructing nasal polyps].
AB  - BACKGROUND: Nasal obstruction may be a causative factor in the etiology of
      obstructive sleep apnea. No studies were found that dealt with the role of nasal
      polyps in sleep apnea. METHOD: Two male patients, 69 and 44 years old, were
      examined in our clinic because of nasal polyps occluding the nasal cavity. Their
      main complaint was nasal breathing obstruction with hyposmia. The clinical
      history revealed snoring but neither apnea nor daytime sleepiness was reported.
      Both patients underwent full nocturnal 12-channel polysomnography (PSG) prior to
      endonasal sinus surgery. PSG and nasal endoscopy were performed 3 months
      postoperatively. RESULT: The patients showed an increased apnea hypopnea index
      (AHI) from 21.1 to 76.6 and 7 to 38.8 respectively. Excessive daytime sleepiness
      (EDS) appeared and relative duration of REM sleep decreased. Nasal CPAP therapy
      was recommended. CONCLUSION: Although patients felt relieved after surgery since
      their nasal breathing problem was solved, the results with respect to AHI, EDS,
      and sleep pattern were unexpected. Perhaps these findings can be explained by
      surgical alteration of nasal receptors or by a postoperative switch from oral to
      nasal nocturnal breathing.

PMID- 9577822
TI  - [Development of a surgical simulator for interventions of the paranasal sinuses.
      Technical principles and initial prototype].
AB  - BACKGROUND: Traditional training methods for surgeons include anatomical studies
      on human cadavers. Limited availability and ethical problems led to the
      consideration of alternatives. The surgeon's level of training could be
      significantly increased by a interactive training system trough computer graphics
      and virtual reality (VR). METHODS: Two main issues addressed are the 3-D
      reconstruction process and 3-D interaction to guide the surgical instruments. To
      provide the virtual environment, a realistic representation of the region of
      interest with all relevant anatomical parts is required. This model has to be
      suitable for computer simulation, while preserving as accurately as possible
      important anatomic features. Therefore the concept of creating a 3-D
      representation semi-automatically was developed. Textures derived from endoscopic
      images are superimposed on the virtual anatomic structures and provide better
      realism. RESULTS: Intuitive handling of the surgical instruments is ensured by
      using the tracking technique. The system allows navigation via a virtual camera
      and interaction with the virtual anatomical structures. Currently the use of a
      force feedback system and the simulation of deformations of tissues is critical.
      CONCLUSIONS: The VR based simulation system offers an alternative to conventional
      training methods. The future role of surgical simulation depends on overcoming
      the current drawbacks to provide greater interactive realism: the integration of
      a force feedback system to simulate the resistance of anatomical structures and
      the simulation of tissue deformations--both currently under development.

PMID- 9577823
TI  - [Clinical and molecular biology studies of respiratory papillomatosis].
AB  - BACKGROUND: Recurrent laryngeal papillomatosis is a benign neoplastic disease
      which is probably caused by but at least associated with the human
      papillomavirus. It can be of significant importance for the affected patients
      because of its recurrent clinical course. A great variety of therapeutic measures
      has been described including the surgical removal either with conventional
      instruments or using the laser. Development of malignancies from papillomas have
      been reported. PATIENTS: The clinical courses of all 95 patients who have been
      treated for laryngeal papillomatosis since 1960 were analysed retrospectively.
      The two most common forms of treatment, surgical removal either conventionally or
      with the use of the laser, were compared. "Hot start" polymerase chain reaction
      and Southern blot hybridization were used to detect HPV DNA. The case reports of
      all patients developing cancer of the larynx are included. RESULTS: Laryngeal
      papillomatosis is a disease of all ages, more often first diagnosed in the first
      and fourth decade. Puberty had no effect on the clinical course. The different
      forms of treatment did not affect the rate of recurrence. However, the rate of
      complications such as tracheostomy and glottic webs was significantly reduced
      after laser surgery. Since the introduction of this new form of therapy no more
      tracheostomies had to be performed on these patients. HPV DNA was found in four
      of five samples (HPV 6:3, HPV 11:1). Squamous cell carcinoma subsequently
      developed in four cases, three of which occurred almost simultaneously and were
      therefore not included. CONCLUSION: The term juvenile laryngeal papillomatosis
      should be replaced by recurrent respiratory papillomatosis. One could then
      distinguish according to the age of onset, i.e., in children below the age of 16
      years and in adolescents and adults older than 15 years. The occurrence of
      squamous cell carcinomas in patients previously treated for papillomas underlines
      the need for repeated histological studies. The surgical treatment remains the
      mainstay in the management of laryngeal papillomatosis. The laser surgical
      technique is superior to conventional removal. Using the at present most
      sensitive and specific methods HPV DNA can be detected in a large percentage of
      laryngeal papillomas.

PMID- 9577824
TI  - [The SCC antigen is not a reliable tumor marker in the ENT area. Value of
      squamous cell carcinoma antigen in diagnosis and follow-up of squamous epithelial
      carcinoma in the head-neck area. Results of a retrospective study over 6 years].
AB  - BACKGROUND: In the early 1970s, progress in chemical analysis allowed the
      assessment of low concentration substances in blood and other body fluids. These
      techniques led to development of hitherto unknown diagnostic facilities which
      were tested with respect to malignant tumors. In those days SCC-A was considered
      a promising substance for aiding in diagnosis and observation in patients with
      SCC. METHODS: This retrospective study investigates the correlation between tumor
      size and tumor progress and the SCC-A level in a group of 322 patients (male: n =
      291, age 24-87 yrs, mean 56 yrs: female: n = 31, age 38-82 yrs, mean 70 yrs).
      RESULTS: The diagnostic value of SCC-A turned out to be poor. In 78%, SCC-A
      levels were low and neither correlated with tumor size nor the presence of
      metastases. In follow-up the situation was even worse: A reliable correlation
      between SCC-A and the course of disease was found in 5.8% of patients only.
      CONCLUSION: The SCC-A could neither reliably contribute to diagnosis nor to
      follow-up of patients with squamous cell carcinomas of the head and neck.

PMID- 9577825
TI  - [The myocutaneous sternocleidomastoid flap for reconstruction of the mouth cavity
      and pharynx].
AB  - BACKGROUND: Among the myocutaneous island flaps applied for reconstruction of
      large soft-tissue defects after ablative surgery for malignomas, the pectoralis
      major flap is the one most frequently used. In comparison, the
      sternocleidomastoid myocutaneous island flap is not as popular. METHODS: We
      report on our experiences with the superiorly based sternocleidomastoid
      myocutaneous (SCM) island flap (cutaneous island of 6-8 cm in diameter) in seven
      consecutive cases after resection of malignomas of the oral cavity and the
      pharynx. The vascularization from the occipital artery is additionally supplied
      by preserving the platysma during preparation of the SCM flap. RESULTS: Only one
      total cutaneous necrosis was observed in a patient who had received prior
      radiation. In the other 6 cases no major complications (necrosis or fistula)
      occurred. CONCLUSION: When the preservation of the sternocleidoid muscle does not
      compromise oncologic principles as in cases with limited lymphe node involvement
      (N0-N1), the SCM flap appears to be a useful and simple technique, particularly
      in female patients compared with the pectoralis major flap, in addition to
      others.

PMID- 9577826
TI  - [A new multivariable sigmoid sinus and dura retractor].
AB  - Retraction of the sigmoid sinus and the dura requires a strong instrument. The
      instruments currently available allow only a limited degree of freedom due to
      their lack of mobility and versatility. A new sigmoid sinus retractor (Micro
      France/Instrumentarium) was designed to facilitate the surgeon's task by offering
      the following advantages: Three-dimensional mobility of the blade: lateral,
      rotatory and longitudinal Safe positioning of the retractor by three sets of
      sharp teeth Fixation of the blade by a single screw Strong retraction without
      giving way.

PMID- 9577827
TI  - [Interesting case no. 10. Cholesteatoma with destruction of the sigmoid sinus
      after thrombosis, with epidural abscess and Benzold abscesses].

PMID- 9577828
TI  - [Restorative operations].

PMID- 9577829
TI  - Psychiatric genetics and prejudice: can the science be separated from the
      scientist?

PMID- 9577830
TI  - The D2 receptor: love it and leave it.

PMID- 9577831
TI  - The usual suspects: tyrosine hydroxylase and the serotonin transporter in
      affective disorders.

PMID- 9577832
TI  - Mapping genes for personality: is the saga sagging?

PMID- 9577833
TI  - Report on the fifth International Congress of Psychiatric Genetics.

PMID- 9577834
TI  - New branches on the neuregulin family tree.

PMID- 9577835
TI  - Cerebellar pathology in BDNF -/- mice: the classic view of neurotrophins is
      changing.

PMID- 9577836
TI  - Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than
      dopamine to brain D2 receptors, yet occupy high levels of these receptors.
AB  - This review addresses two questions. First, why does clozapine apparently occupy
      low levels of dopamine D2 receptors in patients, in contrast to all other
      antipsychotic drugs which occupy 70-80% of brain dopamine D2 receptors? Second,
      what is the receptor basis of action of antipsychotic drugs which elicit low
      levels of Parkinsonism? Antipsychotic doses of clozapine occupy between 0% and
      50% of D2 receptors, as measured in patients by a variety of radioligands. It has
      recently been found, however, that the percent occupancy of a receptor by a drug
      depends on the radioligand used to measure that receptor. Based on this new
      finding, this review concludes that clozapine clinically occupies high levels of
      D2 receptors in the absence of any radioligand. This occupancy is estimated to be
      of the order of 70-80% in the dopamine-rich region of the human striatum, and
      even higher in the limbic D2-containing regions which are low in endogenous
      synaptic dopamine. This conclusion arises from two different approaches. One
      approach is to relate the reported clozapine occupancies in the human striatum
      with the dissociation constants of the various radioligands at the D2 receptor.
      This relation extrapolates to approximately 70-80% occupancy by clozapine when
      clozapine competes with endogenous dopamine at the D2 receptor. The second
      approach is to calculate the D2 occupancy of each antipsychotic drug, using the
      average spinal fluid concentration and the correct dissociation constant of the
      antipsychotic, thereby revealing that all antipsychotic drugs, including
      clozapine, occupy approximately 70-80% of dopamine D2 receptors in the human
      striatum, and possibly higher in the limbic regions. As determined by the new
      dissociation constants, antipsychotic drugs which elicit Parkinsonism
      (trifluperazine, chlorpromazine, raclopride, haloperidol, fluphenazine,
      risperidone) bind more tightly than dopamine to D2, while those antipsychotic
      drugs which elicit little or no Parkinsonism (melperone, seroquel, perlapine,
      clozapine, remoxipride, molindone, sulpiride, olanzapine, sertindole) bind more
      loosely than dopamine to D2 receptors. Compared to the tightly bound
      antipsychotic drugs, the more loosely bound antipsychotics generally require
      higher clinical doses, require fewer days for clinical adjustment, but may
      dissociate from the D2 receptor more rapidly and could lead to clinical relapse
      somewhat earlier than that found with the traditional tightly bound antipsychotic
      drugs.

PMID- 9577837
TI  - A new framework for investigating antipsychotic action in humans: lessons from
      PET imaging.
AB  - With a decade of neuroreceptor imaging of antipsychotics behind us, this article
      attempts to synthesise what has been learnt about the mechanism of action of
      antipsychotics using these techniques. The data show that: (i) the 'typical'
      antipsychotics bind mainly to the dopamine D2 receptor, and that 60-80% D2
      occupancy may provide optimal antipsychotic response with little extrapyramidal
      side effects; (ii) all the clinically available 'atypical' antipsychotics show a
      higher occupancy of the 5-HT2 than D2 receptors; (iii) however, these 'atypical'
      antipsychotics differ in their D2 occupancy. The D2 occupancy of risperidone is
      within the typical range (i.e. > 60%) while that of clozapine is clearly lower (<
      60%); (iv) antipsychotics with combined 5-HT2/D2 antagonism lose some of their
      'atypical' properties if used in doses where their D2 occupancy is too high (>
      80%). Based on these data a framework is suggested wherein antipsychotics may be
      classified on the basis of their D2 and 5-HT2 occupancy in patients at steady
      state while taking clinically relevant doses. Within this framework typical
      antipsychotics are classified as 'high-D2', resperidone as 'high-D2 high-5HT2'
      and clozapine as a 'low-D2 high-5HT2' antipsychotic. The justification,
      limitations and the value of this framework in understanding and investigating
      newer antipsychotics is discussed.

PMID- 9577838
TI  - A meta-analysis and transmission disequilibrium study of association between the
      dopamine D3 receptor gene and schizophrenia.
AB  - We performed a meta-analysis of over 30 case-control studies of association
      between schizophrenia and a bi-allelic, Bali polymorphism in exon 1 of the
      dopamine D3 receptor gene. We observed a significant excess of both forms of
      homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence
      Interval (CI) = 1.07-1.35) in the combined sample of 5351 individuals. No
      significant heterogeneity was detected between samples and the effects did not
      appear to be the product of publishing bias. In addition we undertook an
      independent, family-based association study of this polymorphism in 57
      parent/proband trios, taken from unrelated European multiplex families
      segregating schizophrenia. A transmission disequilibrium test (TDT) showed a
      significant excess of homozygotes in schizophrenic patients (P = 0.004, odds
      ratio (OR) = 2.7, 95% CI = 1.35-5.86). Although no significant allelic
      association was observed, a significant association was detected with the 1-1
      genotype alone (P = 0.02, OR = 2.32, 95% CI = 1.13-4.99). In addition when the
      results of the family-based association study were included in the meta-analysis,
      the homozygosity effect increased in significance (P = 0.0002, OR = 1.23, 95% CI
      = 1.09-1.38). The results of the meta-analysis and family-based association study
      provide independent support for a relationship between schizophrenia and
      homozygosity at the Bali polymorphism of the D3 receptor gene, or between a locus
      in linkage disequilibrium with it.

PMID- 9577839
TI  - Examination of new and reported data of the DRD3/MscI polymorphism: no support
      for the proposed association with schizophrenia.
AB  - The dopamine D3 (DRD3) receptor gene has been implicated in the aetiology of
      schizophrenia as a candidate gene since it combines both the dopamine receptor
      and limbic hypotheses of the disease. Previous association studies of a DRD3/MscI
      polymorphism suggested an increased frequency of homozygosity at the DRD3
      receptor gene in schizophrenia. Homozygosity appeared to be particularly frequent
      in male patients, individuals with family history of the disease and in good
      responders to neuroleptic treatment. Many studies have since examined this
      polymorphism and have altered or extended the original homozygosity hypothesis.
      In this study, we have investigated the distribution of the DRD3/MscI
      polymorphism in 198 Irish schizophrenic patients and 235 ethnically matched
      controls. Patients and controls showed-similar allele and genotype frequencies.
      Furthermore, linkage analysis using two microsatellite markers flanking the DRD3
      gene was performed on 265 Irish schizophrenic families, with substantially
      negative results. Our findings, in combination with a review of previous studies
      do not support a role for the DRD3/MscI polymorphism in the pathogenesis of
      schizophrenia.

PMID- 9577840
TI  - Striatal presynaptic dopamine function in type 1 alcoholics measured with
      positron emission tomography.
AB  - Recent in vivo studies have shown low dopamine D2 receptor and dopamine
      transporter densities among late onset (type 1) alcoholics. We have now studied 6
      [18F]-FDOPA (FDOPA) uptake in 10 type 1 alcoholics and eight matched controls to
      test the hypothesis that striatal presynaptic dopamine function is lower among
      alcoholics. Markedly low FDOPA uptake (Ki) was observed in the left caudate of
      two alcoholic patients, but the mean striatal uptake values of the patient group
      were higher than those of the control group. The greatest difference was observed
      in the mean FDOPA intake in the left putamen, which was 28% higher in the patient
      group (t = 3.00, P = 0.008, d.f. = 16, independent samples t-test), and in the
      right caudate (difference 36%, t = 2.87, P = 0.01). The elevated FDOPA uptake in
      putamen and caudate correlated with poor Wisconsin Card Sorting Test (WCST)
      performance (error %) among alcoholics (correlation coefficients from 0.49 to
      0.56), which suggests that the magnitude of presynaptic dopamine function
      alteration correlates with the degree of disability to modify one's behavior. The
      results do not give support to the hypothesis of generally decreased striatal
      dopamine turnover in type 1 alcoholism, but on the contrary indicate an increased
      presynaptic dopamine function. This may represent a compensatory mechanism to low
      postsynaptic DA function. The low presynaptic DA function observed in the left
      caudate of two patients suggests that type 1 alcoholism may be a heterogeneous
      disorder.

PMID- 9577841
TI  - Linkage analysis of candidate loci in families with recurrent major depression.
AB  - Recurrent major depression, RMD, is characterized by the occurrence of depressive
      episodes in the absence of mania and/or hypomania. In linkage studies, RMD (or,
      in general, unipolar depression) are frequently grouped together with bipolar
      illnesses into a broad definition of affective disorders. However, twin studies
      suggest that RMD and bipolar disorders might have different genetic determinants.
      The objective of this study was to test a set of families with RMD for linkage to
      chromosomes that have been recently proposed to contain susceptibility loci for
      bipolar disorders: chromosomes 16, 18, 21 and the short arm of chromosome 4. We
      analysed five large families from the northern part of Sweden ascertained through
      a proband with RMD and containing several patients with RMD. For the genetic
      analysis, we included only severely affected individuals (those who had at least
      three episodes that required medical treatment) to increase the chances of
      finding a larger degree of genetic determination. The genetic model led to a
      total disease prevalence of 5% in females and 3% in males. We did not find
      significant evidence for linkage to any of the candidate chromosomes in the
      combined family set. Only one of the families showed a slight indication for
      linkage with markers from the pericentromeric region of chromosome 18. A genome
      scan analysis on an extended collaborative family material with severely affected
      individuals with RMD should be performed to evaluate whether RMD and bipolar
      disorders have a different genetic etiology.

PMID- 9577842
TI  - Tyrosine hydroxylase gene in linkage disequilibrium with mood disorders.
AB  - We studied tyrosine hydroxylase (TH) gene variants in mood disorders using
      linkage disequilibrium techniques. One hundred and forty-five inpatients affected
      by bipolar (n = 88) and unipolar (n = 57) disorders, and 84 healthy controls,
      were typed for TH variants using polymerase chain reaction (PCR) amplification.
      TH was associated with mood disorder, with all affected subjects presenting an
      excess of TH*2 allele (chi 2 = 8.30, d.f. = 1; P = 0.004) and lack of the TH*1
      allele (chi 2 = 6.90, d.f. = 1, P = 0.009). Linkage disequilibrium analyses
      confirmed the association. Our results suggest a moderate linkage disequilibrium
      of TH variants with mood disorders.

PMID- 9577843
TI  - Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in
      seasonality and seasonal affective disorder.
AB  - Seasonal variations in mood and behavior (seasonality) and seasonal affective
      disorder (SAD) have been attributed to seasonal fluctuations in brain serotonin
      (5-HT). the short (s), as opposed to the long (l), allele of the 5-HT transporter
      linked polymorphism (5-HTTLPR) has been associated with neuroticism and
      depression. We hypothesized that this short allele would also be associated with
      SAD and with higher levels of seasonality. Ninety-seven SAD patients and 71 non
      seasonal healthy controls with low seasonality levels were genotyped for 5-HTTLPR
      and compared statistically. Patients with SAD were less likely to have the l/l
      genotype (27.8% vs 47.9%; P < 0.01) and more likely to have the s allele (44.8%
      vs 32.4%; P < 0.02) as compared to controls. The three 5-HTTLPR genotypes were
      also differentially distributed in patients and controls (P < 0.03). The SAD
      patients with the l/l genotype had a lower mean seasonality score than did
      patients with the other two genotypes (mean +/- s.d. = 15.3 +/- 2.8 vs 17.1 +/-
      3.4 respectively; P < 0.02). The 5-HTTLPR short allele contributes to the trait
      of seasonality and is a risk factor for SAD, providing further evidence for a
      relationship between genetic variation in the 5-HT transporter (5-HTT) and
      behavior.

PMID- 9577845
TI  - [Psychiatric practice in its 25th year].

PMID- 9577844
TI  - Interleukin-1 beta and interleukin-1 receptor antagonist do not affect glutamate
      release or calcium entry in rat striatal synaptosomes.
AB  - The cytokine interleukin-1 beta (IL-1 beta) has been implicated in various forms
      of neurodegeneration, and several lines of evidence indicate that it also
      modulates synaptic transmission in the central nervous system. Excessive release
      of the excitatory neurotransmitter L-glutamate results in cell death and probably
      mediates many neurodegenerative conditions. We set out to test the hypothesis
      that involvement of IL-1 beta in neurodegeneration results in some interaction
      with excitatory amino acid-mediated synaptic transmission in the rat striatum,
      either by modifying glutamate release or actions. Presynaptic effects of IL-1
      beta and the IL-1 receptor antagonist (IL-1ra) on glutamate release and calcium
      entry were investigated in isolated nerve terminals (synaptosomes) prepared from
      the striatum. In order to evaluate the involvement of IL-1 in neuronal damage
      caused by glutamate receptor over-activation, the effect of IL-1ra was studied on
      N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA) receptor-mediated brain damage in the rat striatum and
      cortex in vivo. Neither rat recombinant IL-1 beta (rrIL-1 beta: 0.01-2 nM) or
      human recombinant IL-1ra (hrIL-1ra: 0.2 microM) had any significant effect on the
      KCl-evoked glutamate efflux or calcium entry in striatal synaptosomes, indicating
      that their actions are unlikely to be presynaptic. In contrast, intrastriatal
      infusion of hrIL-1ra markedly inhibited (by 43-46%, P < 0.05) neuronal damage
      caused by striatal NMDA or AMPA receptor activation in the rat in vivo, whereas
      no effect was seen on damage induced in the cortex. Thus, our data suggest that
      IL-1 beta and IL-1ra influence neuronal damage in the striatum by acting to
      modify events that occur after excitatory amino acid receptor activation.

PMID- 9577846
TI  - [Pharmacologic interactions of antibiotics and psychotropic drugs].
AB  - By and large, pharmacokinetic interactions are described: macrolide antibiotics,
      isoniazid, ciprofloxacin and ampicillin can lead to toxic concentrations of
      psychotropic drugs, while rifampicin causes subtherapeutic levels. Vice versa,
      carbamazepine might induce subtherapeutic plasma concentrations of doxycycline.
      These interactions are caused by inhibition or induction of the hepatic
      cytochrome P450 enzyme system. Case reports suggest lithium intoxication through
      concomitant use of tetracycline, metronidazol and spectinomycin, which is
      contradicted by animal studies. Clinical symptoms depend on the therapeutic index
      of a given drug, e.g. toxic and subtherapeutic levels are described for clozapine
      but not for haloperidol. No relevant pharmacodynamic drug-drug interactions are
      described, although, the author emphasises psychiatric side effects of macrolide
      antibiotics, isoniazid, beta-lactam antibiotics and fluoroquinolones. On the
      whole, drug-drug interactions of antibiotics and psychotropics seem rare and
      usually benign, though more subtle interactions might be overlooked.

PMID- 9577847
TI  - [The adolescent psychiatry department: organization and initial experiences].
AB  - As in most parts of Switzerland, there was a lack of possibility to hospitalise
      adolescents in specialised psychiatric wards. In 1993, after a long preparatory
      period, it became possible to admit the first patient to the newly established
      adolescent psychiatric department at Basel, a subunit of the university hospital.
      The department is conceived as an open ward, where patients are being cared for
      by an interdisciplinary team of psychiatric nurses and paedagogics, besides many
      other professionals. Milieutherapeutic techniques, psychotherapy and
      pharmacotherapy are practised side by side. The conceptional ideas, gradual
      building of the ward and the experience of the first three years clinical
      experiences are summarised in this article.

PMID- 9577848
TI  - [Treatment prognosis and discharge 2 years later. III. Berlin
      Deinstitutionalization Study].
AB  - In a two-year follow-up we report on discharges in a cohort of 422 middle-term
      and long-term inpatients and prognoses of their psychiatrists and psychologists
      concerning time of discharge and location, after 50% long-term patients with a
      present stay of more than two years and 82% of middle-term patients (stay: 6-24
      months) had been discharged. More than one-third of the long-term patients could
      be placed in sheltered accommodation, but 42% are still referred to nursing
      homes. All together 68% are still in institutional settings--either as inpatients
      or in nursing homes. Prognoses were not very reliable concerning the time of
      discharge but substantial with regard to placement in sheltered accommodation.
      This can be interpreted as a result of successful co-operation between inpatient
      and community-based services.

PMID- 9577849
TI  - [The psychiatric department evaluated by patients. A user survey as part of
      quality assurance in psychiatry].
AB  - Prior to discharge 351 patients in a psychiatric ward of a general hospital were
      requested to complete a 31-question survey pertaining to their hospital stay. The
      highest marks were given to the nursing staff and the individual psychiatric
      therapy. The survey also reflected dissatisfaction with the doctors' rounds led
      by the medical director, the information given about the medications and the
      early morning exercise programme. RESULTS: The patients were very cooperative and
      took the questions seriously. The questionnaire should not contain more than 10
      clear and simple questions. The very act of posing the questions to the patients
      brought about changes in the ward.

PMID- 9577850
TI  - [Occupational rehabilitation of chronic psychiatric patients. Results of a
      prospective study over 3 years].
AB  - Vocational rehabilitation of mentally ill patients is now focused outside the
      psychiatric hospital. Three types of programmes play a major role: outpatient
      work therapy programmes at psychiatric hospitals, jobs in (partly) sheltered
      employment facilities as in companies specially adapted for employing mentally
      ill persons, and workshops for the mentally disabled. In the north-western German
      region of Westphalia-Lippe (population: 9 million) we carried out a three-year
      prospective study on a regionally representative sample from such rehabilitation
      institutions to assess the course and outcome of vocational rehabilitation. The
      sample comprised 295 men and 176 women with a mean age of 36.1 year (+/- 9.6).
      The majority were chronically ill patients with a history of frequent long-term
      hospitalisation. 61% of all probands were suffering from schizophrenic disorders.
      The outcome of vocational rehabilitation differs substantially among the three
      programme types, primarily due to varying baseline conditions, subjective
      expectations or goals, and courses of illness. The programmes are not
      alternatives but should be seen as supplementary components of a care system
      which has to meet a wide range of patient requirements. Vocational integration
      into the open labour market is a desirable and realistic objective for only some
      of those concerned.

PMID- 9577851
TI  - [Psychotic processing and psychotic gestalt of somatic symptoms: the risk of
      diagnostic errors].
AB  - We report on a 50-year old patient who on admission to hospital demonstrated
      several disorders of sensation of her body which seemed to be bizarre and
      exclusively caused by a psychotic disorder. It soon turned out that a
      somatological disorder was of primary importance. The symptoms of the somatic
      disorder had been assimilated and shaped psychotically. This serves to show that
      every patient should be examined carefully for somatic disorders regardless of
      whether existing disorders of sensation are bizarre or not.

PMID- 9577852
TI  - [Charles Bonnet syndrome].
AB  - An 80-year old previously healthy woman with recent onset of binocular macular
      degeneration presented for clinical psychiatric evaluation of elaborate complex
      visual hallucinations. In the absence of other organic or psychiatric findings
      the patient maintained insight into the unreal nature of her visions. As
      neuroleptic drugs showed no effect, low dose treatment with carbamazepin resulted
      in disappearance of hallucinations. The phenomenon of Charles-Bonnet-syndrome is
      discussed as an example of a neuro-psychiatric hallucinosis.

PMID- 9577853
TI  - [Acute mental disorders of alcoholic patients. By Karl Bonhoeffer, Gustav Fischer
      Publications, Jena 1901].

PMID- 9577854
TI  - Reality and danger in psychoanalytic treatment.
AB  - In recent papers there has been considerable interest in the disclosure of the
      analyst's erotic countertransference. In our view this discussion touches a more
      fundamental issue: must something "real" take place between analyst and patient
      in order for real change to occur? And if what takes place is "real," will it not
      be dangerous and potentially destructive? Tracing the history of psychoanalytic
      understandings of what is "real" in the patient's life and what is "real" in the
      transference, we explore these questions in a clinical vignette and discuss the
      implications of this issue for our understanding of the process of psychoanalytic
      treatment.

PMID- 9577855
TI  - Neuropsychological dysfunction and psychological conflict.
AB  - The author examines the interplay between neuropsychological dysfunction and
      psychological conflict. Two ideas are emphasized. First, clinicians may overlook
      or subtly de-emphasize the contribution of neuropsychological dysfunction to
      patients' difficulties. Second, when neuropsychological difficulties are
      diagnosed, there is value in being acquainted with the details of the dysfunction
      and exploring the specific ways in which they are elaborated in fantasy and
      interwoven in the patient's psychodynamic constellation (including their
      employment for defensive and superego purposes). This perspective is contrasted
      with more general formulations concerning the patient's experience of her/
      himself as damaged. A case serves to illustrate such a clinical process of
      discovery.

PMID- 9577856
TI  - Self psychology since Kohut.
AB  - The changes in psychoanalytic self psychology since its origination by Heinz
      Kohut are described as differences in three branches: the traditional, the
      intersubjective, and the relational. Each claims both a distinctiveness and a
      major influence within self psychology. These are described and contrasted. It is
      suggested that an effort to integrate all three is premature, and that they will
      continue to grow separately.

PMID- 9577857
TI  - The complexities and pitfalls of working with the countertransference.
AB  - The author attempts to demonstrate that the usual manner of reporting
      countertransference experiences does not do justice to the complexity of these
      phenomena. Clinical illustrations are used to show that the data of
      countertransferences are partial, often difficult to use immediately in analyses,
      sometimes ambiguous, and hard to validate. The fate of persistent conflictual
      residues within each analyst is discussed in the context of the life cycle of
      psychoanalytic work.

PMID- 9577858
TI  - Female genital anxieties: views from the nursery and the couch.
AB  - The author evaluates developmental and clinical data concerning female genital
      anxieties in an attempt to address the question of its clinical utility. An
      effort is made to clarify evidence for female genital anxiety as distinct from
      castration anxiety in females in the clinical situation and in development. This
      paper examines these concepts from the perspective of the author's detailed
      observational and clinical data, which are central to this report.

PMID- 9577859
TI  - Is psychoanalysis an experimental procedure or a reflection of subjective life?
AB  - Psychoanalysis fits comfortably into the model of neither an experimental
      procedure nor a subjective experiencing. Yet it elicits both the deep-running
      skepticism of science and the passions of everyday life. A structure for
      incorporating both is suggested.

PMID- 9577860
TI  - [Interventional MR tomography. Current status and future perspectives].
AB  - The concept of MR guidance of invasive diagnostic and minimally invasive
      therapeutic procedures is based on the excellent morphologic and functional
      properties of MR imaging. Prerequisites are adequate patient monitoring and
      adherence to safety guidelines. Fast and ultrafast sequences, temperature
      quantification, visualization of intravascular devices, thermal stability of
      contrast media and thermosensitive contrast media are discussed. The spectrum of
      clinical applications includes biopsies, thermal ablation modalities, vascular
      applications, MR endoscopy and intraoperative MR imaging. The development of
      interventional MR imaging is still in its infancy. In the future, MR imaging may
      play an important role in interventional radiology and minimally invasive
      therapy.

PMID- 9577861
TI  - [Interventional MR tomography: equipment concepts].
AB  - Interventional MRI is one of the most recent developments of clinical MR imaging.
      Because of the development of open MR systems and very compact high-field
      systems, a number of interventional procedures are already possible today under
      MR control and will be tested in experimental and clinical investigations. The
      currently commercially available systems differ with respect to their static
      magnetic field strength, their gradient systems and patient access. In addition,
      there are differences concerning their space requirements and costs. All systems
      have components facilitating interventional procedures. In this article we
      discuss the advantages and shortcomings of these commercially available systems
      and look at future developments in interventional MR equipment.

PMID- 9577863
TI  - [Pulse sequences and visualization of instruments].
AB  - While initially advocated primarily for intrasurgical visualization (e.g.,
      craniotomy), interventional MRI rapidly evolved into roles in image-guided
      localization for needle-based procedures, and thermal ablation of cancer. In this
      contest, MRI pulse sequences and scanning methods serve one of four primary
      roles: (1) speed improvement, (2) device localization, (3) anatomy/lesion
      differentiation and (4) temperature sensitivity. The first part of this
      manuscript deals with passive visualization of MR-compatible needles and the
      effects of field strength, sequence design, and orientation of the needle
      relative to the static magnetic field of the scanner. Issues and recommendations
      are given for low-field as well as high-field scanners. The second part contains
      methods reported to achieve improved acquisition efficiency over conventional
      phase encoding (wavelets, locally focused imaging, singular value decomposition
      and keyhole imaging). Finally, the last part of the manuscript reports the
      current status of thermosensitive sequences and their dependence on spinlattice
      relaxation time (T1), were diffusion coefficient (D) and proton chemical shift
      (delta).

PMID- 9577862
TI  - [Operation of multidisciplinary, interventional 0.5 Tesla magnetic resonance
      tomograph. Technical and logistic problems and initial clinical results].
AB  - Multidisciplinary usage of a MRI system with a superconducting 0.5-T magnet
      (Signa SP, General Electric) with a vertical gap suited for diagnostic and
      therapeutic interventions raises complex problems. The MR equipment, including a
      special localizing system and the instruments for diagnostic and therapeutic
      interventions, is described. Before putting the system into operation tests were
      necessary to check MR compatibility of various materials and instruments and to
      build some auxiliary equipment. We report on the coordinating activities of the
      radiologist in the context of MR use by different medical specialities. Within
      the course of 12 months, 428 examinations/interventions of different kinds were
      carried out, among them 75 functional examinations of the spine or of joints, 31
      diagnostic biopsies, 23 cerebral biopsies, and 23 operations. The special design
      of the Signa SP allows the whole scale of functional examinations, up to complete
      neurosurgical interventions, in the sitting position and under nearly real-time
      imaging control.

PMID- 9577864
TI  - [MRI-controlled biopsies].
AB  - Biopsies were the first "intervention" under MR guidance. After initial
      difficulties concerning ferromagnetic biopsy instruments and the design of MR
      scanners, the latest technological improvements rendered MR guidance for biopsies
      more feasible. In this article we illustrate present-day clinical experience in
      the field of abdominal, breast and bone biopsy. Important aspects regarding the
      different designs of "interventional" MR scanners and the visualization of
      instruments for biopsy are discussed.

PMID- 9577865
TI  - [Control and monitoring of focal thermotherapy with magnetic resonance
      tomography. An overview].
AB  - Minimally invasive thermotherapies for focal tissue destruction on the basis of
      laser-, microwave-, focused ultrasound-, or cryogen-induced changes of tissue
      temperature represent an alternative to surgical tissue ablation, particularly in
      the treatment of tumors. The thermotherapy modalities listed necessitate indirect
      guidance and monitoring, since they often do not lend themselves to immediate
      visual control. In the brain, in head and neck tumors, in the liver, and in the
      prostate, MRI reliably and accurately delineates both the positions of
      interstitial thermotherapy applicators and--in contrast-enhanced, T1-weighted
      images--the perfusion defects in tissue necrosis induced by thermotherapy. The
      transfer of results of in-vitro and in-vivo model studies to assess interstitial
      temperature and lesion development during thermotherapy to the actual treatment
      of patients, however, is still in an initial phase. Further development of both
      rapid MRI sequences and MRI scanners suited for interventions will show how far
      treatment systems and guidance systems can be adapted to one another.

PMID- 9577866
TI  - [Vascular applications of interventional MRI].
AB  - The flow sensitivity inherent to the MR experiment allows for the non-invasive
      assessment of both the arterial and venous vasculature in any desired plane with
      good spatial resolution. Data can be acquired in a three-dimensional form,
      permitting reformating in any plane. In addition, MRI is capable of providing
      quantitative blood flow information with the use of phase-contrast flow-mapping
      techniques. Ultrafast gradient echo and echoplanar data acquisition strategies
      even permit imaging in near-real time. The availability of open MRI
      configurations now permits one to take advantage of the unique imaging features
      inherent to MR imaging for the purpose of guidance and control of various
      intravascular procedures. With the recent development of the MR tracking and MR
      profiling techniques, permitting visualization of guide-wires and catheters
      relative to their surroundings in the MR environment in real time, one of the
      last obstacles to 'Interventional MR angiography' has in effect been overcome. In
      addition, MR catheters can be modified to acquire high-resolution MR images of
      the vascular wall, thereby opening vast possibilities regarding characterization
      of atherosclerotic plaques. This review introduces the underlying techniques for
      catheter and guide-wire visualization in the MR environment, describes
      preliminary interventions in animals and humans and discusses the potential of
      intravascular MRI.

PMID- 9577867
TI  - [Intraoperative magnetic resonance tomography for control of extent of
      neurosurgical operations].
AB  - PURPOSE: The main aim of our study was to find out whether the combined use of
      neuronavigation and intraoperative MRI can increase the rate of "complete tumor
      removal". The second aim was to characterize the different forms of surgically
      induced enhancement in order to differentiate them from residual tumor. MATERIALS
      AND METHODS: Surgery was performed in 18 patients with high-grade glioma. Using a
      neuronavigation device, the surgeons operated up to the point where they would
      otherwise have terminated surgery. Intraoperative MRI was then performed to
      determine whether residual enhancing had been left behind and to update the
      neuronavigation device. If necessary, feasible surgery was continued. On days 1-3
      after surgery early postoperative MRI (1.5 T) was performed. The proportion of
      patients in whom the enhancing tumor was completely removed was compared with a
      series of 60 patients with glioblastoma multiforme, who had been operated on
      using neither neuronavigation nor intraoperative MRI. We also looked for and
      characterized different types of surgically induced enhancement. RESULTS:
      Intraoperative MRI definitely showed residual tumor in 6 of the 18 patients and
      resulted in ambiguous findings in 3 patients. In 7 patients surgery was
      continued. Early postoperative MRI showed residual tumor in 3 patients and
      resulted in uncertain findings in 2 patients. The rate of patients in whom
      complete removal of enhancing tumor could be achieved was 50% at the time of the
      intraoperative MR examination and 72% at the time of the early postoperative MR
      control. The difference in proportion of patients with "complete tumor removal"
      between the groups who had been operated on using neuronavigation (NN) and
      intraoperative MRI (ioMRI) and those who had been operated on using only modern
      neurosurgical techniques except NN and ioMRI was statistically highly significant
      (Fisher exact test; P = 0.008). Four different types of surgically induced
      contrast enhancement were observed. These phenomena carry different confounding
      potentials with residual tumor. CONCLUSION: Our preliminary experience with
      intraoperative MRI in patients with enhancing intraaxial tumors is encouraging.
      Combined use of neuronavigation and intraoperative MRI was able to increase the
      proportion of patients in whom complete removal of the enhancing parts of the
      tumor was achieved. Surgically induced enhancement requires careful analysis of
      the intraoperative MRI in order not to confuse it with residual tumor.

PMID- 9577868
TI  - [Detection of an abdominal space-occupying lesion with CT after surgery of
      duodenal ulcer. Mycotic infected aneurysm of the gastroduodenal artery as a
      complication after surgery of duodenal ulcer].

PMID- 9577869
TI  - [Inverse radiotherapy planning for intensity modulated photon fields].
AB  - Substantial improvement in conformal radiotherapy is possible using modulated
      irradiation fields. Such modulated fields may be generated even with conventional
      accelerators by means of individual metal compensators or with the recently
      available dynamic multileaf collimators (MLC). For treatment planning a new kind
      of planning program is required that can calculate the 2 D-intensity matrices for
      each photon field. At the German Cancer Research Center (Deutsches
      Krebsforschungszentrum) such a program has been developed under the name of
      "KonRad" (Conformal Radiotherapy). Although it is an independent application, it
      is proposed for clinical usage to supplement a planning system that is already
      present. So-called inverse planning differs from conventional 3 D planning, as
      the trial-and-error approach for finding good field parameters is nearly
      completely avoided. Instead, the radio-oncologist is given the chance directly to
      specify medically oriented criteria like the prescription dose in the target
      volume, maximal tolerance dose values for each organ at risk and their weighting
      factors. In addition, the so-called DVH optimization allows aimed, partial
      overdosage, especially in parallelly structured organs in order to obtain better
      overall planning results. Because of very fast dose calculation in connection
      with rapidly converging gradient optimization and an intuitive use interface, the
      planning is done in a comfortable and interactive manner. Using a workstation or
      a PC, a typical plan can be created within a few minutes.

PMID- 9577870
TI  - [Long-term home oxygen therapy: who? with what? how expensive?].
AB  - Since 1981 long-term oxygen therapy (LTOT) has become an important procedure for
      the rehabilitation of patients with chronic respiratory insufficiency in
      Switzerland too. As a result of long-term clinical experience as well as
      technical progress, there is, however, increasing need for an updated
      reassessment of guidelines and standardized management respectively: the
      indications for LTOT-so far restricted to patients with COPD-are extended to
      patients with pulmonary diseases other than COPD associated with chronic
      hypoxemia (pO2 < 7.3 kPa) provided there is enough evidence of clinical benefit.
      Another important aspect of LTOT focuses on the appropriate application of
      different oxygen sources. Oxygen concentrators are still accepted to be the most
      economic domiciliary source. For short-term outdoor activities, small portable
      cylinders in combination with an oxygen conserving system should be used.
      However, in regular mobile oxygen therapy liquid oxygen is the best choice,
      generally consisting of a domiciliary reservoir and portable canisters. Delivery
      of oxygen through a transtracheal catheter is superior to nasal cannula because
      of lower oxygen consumption, decreased breathing work and improved compliance
      respectively. To organize and follow-up LTOT in Switzerland, a very efficient
      concept was introduced many years ago which is characterized by economical
      cooperation between physicians, insurances, technical suppliers and social
      providers. Today more than 3000 patients-corresponding to 38/100,000 inhabitants
      benefit from LTOT. Future perspectives should target an earlier start to
      continuous as well as mobile LTOT, in order to improve rehabilitation in still
      active conditions instead of merely palliating the terminal stages.

PMID- 9577871
TI  - [Pulmonary emphysema: indications for surgical treatment].
AB  - Pulmonary emphysema is defined as abnormal irreversible enlargement of airspaces
      distal to the terminal bronchioli, accompanied by destruction of their walls and
      without obvious fibrosis. It occurs usually as a consequence of smoking. Advanced
      stages of emphysema lead to dyspnea and are associated with airflow obstruction,
      hyperinflation and reduced diffusing capacity. Measures that have been shown to
      alter the course of the disease are smoking cessation and long-term oxygen
      administration to correct arterial hypoxemia. Antibiotics, bronchodilators,
      corticosteroids and rehabilitation may provide symptomatic relief. Surgery is
      another treatment option for selected cases. Recurrent pneumothoraces resulting
      from rupture of subpleural bullae may be prevented by thoracoscopic pleurodesis.
      Large bullae that compress adjacent lung and mediastinal structures may be
      resected. In selected cases of diffuse advanced emphysema associated with
      significant hyperinflation, volume reduction by resection of the most destroyed
      areas of the lungs may improve dyspnea, pulmonary function and exercise
      tolerance. In severely symptomatic patients with reduced life expectancy due to
      endstage emphysema, lung transplantation may provide with dramatic symptomatic
      and functional improvement. If the indications for operation are carefully
      considered and the intervention is performed by an experienced team, surgery is a
      valuable treatment modality in certain patients with pulmonary emphysema.

PMID- 9577872
TI  - [Pleural effusion: what next?].
AB  - This article gives an overview of the aetiology, diagnostic evaluation and
      treatment of pleural effusions. A systematic approach including radiological and
      sonographic examinations and pleural fluid analysis is proposed with a view to
      selecting the most appropriate therapy. Common forms of exudative pleural
      effusions are explained in detail. For complicated parapneumonic effusions, new
      therapeutic options such as the use of fibrinolytics or thoracoscopic debridement
      are discussed. Talc slurry and thoracoscopic talc poudrage provide effective
      methods for pleurodesis in case of malignant effusions.

PMID- 9577873
TI  - [Complex differential diagnosis of diffuse fine nodular lung infiltrates].
AB  - We report the case of a 36-year-old, previously healthy male patient presenting
      with progressive shortness of breath and dry cough. Chest X-ray revealed a
      diffuse micronodular interstitial pattern and pulmonary function tests showed
      reduced diffusion capacity, a restrictive pattern and obstructive airflow
      limitation. Transbronchial biopsy disclosed lymphangiosis carcinomatosa. The
      primary tumor was adenocarcinoma of the stomach. Differential diagnosis and the
      diagnostic approach to interstitial lung diseases are discussed. History,
      clinical findings, radiological and functional tests, as well as blood chemistry,
      serve to narrow down the differential diagnosis. The main further investigative
      steps are bronchoscopy with broncho-alveolar lavage and transbronchial biopsies,
      high resolution computer tomography, and thoracoscopic biopsy.

PMID- 9577874
TI  - [25 years after CO poisoning].

PMID- 9577875
TI  - [HLA genotyping: indications and limits].
AB  - The polymorphism of the class I (HLA-A, B, C) and class II (HLA-DR, DQ, DP)
      antigens was for a long time investigated using serological methods. Today
      molecular biology methods are available to define the numerous HLA alleles by
      genotyping [(82 HLA-A alleles, 174 HLA-B, 38 HLA-C, 166 HLA-DRB1, 27 HLA-DQB1, 71
      HLA-DPB1) (nomenclature 1996)]. Many different molecular biology methods can be
      used to define these alleles (PCR- RFLP, PCR-SSOP, PCR-SSP, PCR-SBT), the choice
      of method depends on the number of genotypes achieved per day and the time
      required to obtain a result. The resolution degree of results can reach two
      levels: low resolution: provides results almost identical to those obtained by
      serological methods. Low resolution is sufficient to find HLA-identical siblings
      for bone marrow transplantation, to type organ donor-recipient pairs and for
      diagnosis in most HLA disease associations; high resolution: defines HLA allele
      subtypes. High resolution is essential to type bone marrow donor-recipient pairs
      when the donor is unrelated. Molecular biology methods will gradually replace
      serological methods in the future. The only restriction is that some alleles,
      defined at the genomic level, are not expressed at the cell surface and are thus
      not functional.

PMID- 9577876
TI  - Platelet and neutrophil alloantigen genotyping in clinical practice.
AB  - Immune responses to platelet and neutrophil alloantigens are involved in the
      pathogenesis of several clinical syndromes including: neonatal alloimmune
      thrombocytopenia (NATP), post-transfusion purpura (PTP), refractory responses to
      platelet transfusion, neonatal alloimmune neutropenia (NAN), transfusion-related
      acute lung injury (TRALI), and chronic benign autoimmune neutropenia of infancy.
      Initially, platelet alloantigens were only characterized serologically.
      Subsequently, they were localized to specific platelet surface glycoprotein
      structures and ultimately defined to the level of nucleic acid polymorphisms on
      platelet glycoprotein genes. These advances allowed the tools of molecular
      biology to be applied to typing for platelet alloantigens. The advantages of such
      typing methods include: 1) patient platelets are no longer required for the
      typing assays, and therefore, platelet types can be established on extremely
      thrombocytopenic samples (by using peripheral blood white blood cells [WBC]); 2)
      The genotyping methods eliminate the requirement for rare serologic reagents. A
      number of different genotyping methods have been developed. These include:
      restriction fragment length polymorphism (RFLP), sequence specific primers (SSP),
      and Dot-Blot hybridization. Clinical applications of this methodology include:
      determining the platelet genotype of fetuses at risk for NATP, in the diagnosis
      of PTP, and identifying causes of refractory responses to platelet transfusions.
      Analogous to platelet alloantigens, a limited number of neutrophil alloantigens
      can now be determined by molecular biologic methods. The new methods obviate the
      need to isolate fresh neutrophils for serologic typing and do not require rare
      serologic reagents. To date, molecular polymorphisms associated with alloantigens
      on the neutrophil Fc gamma RIIIb surface glycoprotein have been elucidated. These
      include the allo-antigens NA1, NA2, and SH.

PMID- 9577877
TI  - [Molecular biology and transfusional viral safety].
AB  - In this review we present four fields to which viral molecular biology has
      contributed: the discovery of blood-borne viruses and the knowledge of the
      natural history of infection by these viruses; the validation of the results of
      virological assays used in the biological screening of blood donations; the
      contribution of molecular biology in inquiries into viral transfusional
      contamination; the interest of molecular biology in viral transfusional
      epidemiology. We subsequently deal with the parameters of the discussion on the
      impact and the feasibility of a systematic screening of several viral genomes in
      blood donations.

PMID- 9577878
TI  - [Importance of molecular biology in retrovirus and herpesvirus infections].
AB  - Molecular biology has long been used as a tool for basic research in virology.
      Its medical use is recent and has been supported both by numerous technical
      improvements and the discovery of new human viruses. This is illustrated by the
      emergence of human immunodeficiency virus (HIV)-1, HIV-2, human T-cell leukemia
      virus (HTLV)-I/II, and human herpesviruses (HHV) 6, 7 and 8. Polymerase chain
      reaction (PCR) gave a major boost to an extended use of molecular biology
      techniques. This resulted in a better knowledge of human viral infections as
      illustrated by studies on HIV and HHV-8. New viruses have been characterized.
      Molecular markers have permitted analysis of virus transmission cases,
      classification of genetic variants and detection of mixed infections. The
      quantitation of viral load has led to a better understanding of chronic
      infections and reactivations. As a tool for diagnosis, molecular biology is not
      yet considered as a universal alternative to classical procedures such as
      serology and antigen detection. However, major improvements in molecular biology
      techniques might question current diagnosis strategies in the very near future.

PMID- 9577879
TI  - [Dendritic cells: a complex cellular system].
AB  - Dendritic cells (DC) are the most potent antigen-presenting cells. Thus, ex vivo
      antigen-pulsed DC are a potentially powerful tool to induce in vivo immunity
      against tumor-associated or viral antigens. Therefore, culture methods to
      generate high numbers of DC from bone marrow or blood CD34+ hematopoietic
      progenitor cells have recently been developed. These methods, which use different
      combinations of growth factor--mainly granulocyte/macrophage colony-stimulating
      factor (GM-CSF), tumor necrosis factor (TNF)-alpha and interleukin (IL)-4--make
      the characterization of DC obtained from CD34+ cells of different origins easier
      and allow to assess whether DC relate to a unique or distinct differentiation
      pathways. Monocytes and even macrophages can also directly differentiate into DC
      in the presence of GM-CSF and IL-4. This has to be reconciled with evidence
      supporting earlier branching off of the macrophage and DC lineages, and raises
      questions as to the identity of the latter lineage. Apart from DC of myeloid
      origin, DC may also originate from lymphoid progenitors. Because the capacity of
      DC to capture, process and present antigens is known to vary according to their
      differentiation stage, and lymphoid DC might behave differently from lymphoid DC
      in this respect, the definition of which type of DC to use for immunotherapy must
      be more precise, in order to avoid detrimental side effects or results. From a
      practical point of view, it is also necessary to define the most appropriate
      cytokine combinations and schedules thereof to optimize proliferation and
      differentiation of DC from different origins. These conditions should then be
      applied to generated DC for their efficient and safe use for clinical
      immunotherapy.

PMID- 9577880
TI  - [Cord blood banks--unrelated transplants].
AB  - Hematopoietic progenitor cells are present in umbilical cord blood; placental
      blood (PB) previously considered as waste product now constitutes an alternative
      source of hematopoietic stem cells for bone marrow reconstitution. This has
      promoted the establishment of cord blood banks for use in unrelated transplants.
      The banking of PB offers many advantages: the donors do not require anesthesia,
      stored PB can be a valuable source of stem cells for patients from ethnic
      minorities underrepresented in volunteer registers, and stored PB can be made
      available much faster than bone marrow from unrelated donors. Preliminary
      clinical experience suggests that, due to the immunological immaturity of PB
      cells, graft versus host disease might be lower than when using bone marrow from
      adult donors and HLA restrictions might be less stringent. If the number of
      nucleated cells in PB often appears low for patients weighing more than 40 kg,
      clinical data suggest that the number of stem cells may be sufficient for adult
      transplantation. The number of cord blood banks throughout the world is
      increasing rapidly. In the USA and Europe, more than 10,500 PB units are stored
      and available for transplantation. In the next 5 years, a total of 50,000 PB will
      be reached which may be sufficient to provide for the majority of candidates for
      unrelated BM transplantation. The practices of umbilical cord blood collection,
      mother selection, infectious disease screening, cell manipulation and storage
      must be standardized. Some accreditation process should be mandatory for
      assessing operating procedures and the quality assurance programs of the banks,
      and for allowing the international exchange of placental blood between transplant
      centers.

PMID- 9577881
TI  - Leukocyte depletion: a biotechnical transfusion story.

PMID- 9577883
TI  - [Use of islet cells in cell therapy].
AB  - Insulin dependent diabetes mellitus is a common disease affecting 1.5 million
      patients in Europe. It is currently treated by multiple injections of insulin
      associated with blood glucose self monitoring. The goal of the treatment is to
      obtain near normal glucose concentration, in order to prevent the later
      complications (retinopathy, nephropathy, neuropathy, macroangiopathy) of the
      disease--which may be severe--while avoiding severe hypoglycaemia. Although
      diabetes therapy has improved enormously in the last few decades, intensive
      research is currently aimed at replacing not only the missing hormone but also
      the cells which normally produce insulin in the pancreas. Transplantation of
      insulin secreting cells as a treatment of diabetes mellitus therefore has a
      special significance among other applications of cell therapy, since it deals
      with a disease which already has an efficient therapy. The aim of this article is
      the discussion of the objectives and the hopes in this field.

PMID- 9577882
TI  - [Hepatocytes in cell therapy].
AB  - Cell-based therapy could represent an alternative treatment to orthotopic liver
      transplantation in acute liver failures and for the correction of genetic defects
      of various enzymatic functions. Several recent studies indicate that hepatocytes
      injected either in the spleen or in portal vein can restore liver-specific
      function(s) in animal model systems. Alternatively, an extracorporal hybrid
      bioartificial liver might provide liver-specific functions, maintain the patient
      alive and allow spontaneous recovery of the patient's own liver, or act as a
      bridge toward liver transplantation in acute liver failures. Various drawbacks of
      devices such as flat culture substrates, hollow-fiber bioreactors or
      microcarriers led us to develop a reliable extracorporeal bioartificial liver
      based on alginate-entrapped hepatocytes. This system was used successfully for
      the correction of the Gunn rat genetic defect which results in the lack of
      bilirubin conjugation. The development of this system for clinical purposes
      requires large yields of functional hepatocytes. We isolated porcine hepatocytes
      by collagenase perfusion of the liver and cells were immobilized within alginate
      beads which were subsequently inoculated in a bioreactor. Porcine hepatocytes
      expressed liver-functions at high levels, particularly those involved in
      detoxification and biotransformation processes; they were immunoisolated from
      immunoglobins and could be cryopreserved. This system represents a promising tool
      for the design of an extracorporeal bioartificial liver in human beings.

PMID- 9577884
TI  - [Developments in ultrasound. Retrospect and prospects after 18 years of
      "Ultrasound in Medicine"].

PMID- 9577885
TI  - [Processes and values of ultrasound diagnosis].

PMID- 9577886
TI  - [Endosonographic imaging of the adrenal glands: a new method].
AB  - In contrast to the reliable imaging of the adrenal gland in infants and children,
      transabdominal sonography of the adrenal glands is often unsuccessful. AIM: To
      improve the imaging of the adrenal glands with high resolution in order to obtain
      information on even small changes in these organs. METHOD: Adrenal glands taken
      from human cadavers were investigated using a 7.5 MHz transducer. Thereafter,
      endosonographic imaging was investigated in 5 human cadavers using an
      endosonoscope PENTAX FG32 UA (longitudinal sector scanning. 7.5 MHz).
      Furthermore, the adrenal glands were imaged in a total of 30 patients with
      different indications for endosonography. RESULTS: The adrenal glands in 5 human
      cadavers could be identified in each case. This was proved in one human cadaver
      by endosonographically guided fine needle puncture with consecutive preparation
      of the tissue damage caused by the needle. In a total of 30 patients with 56
      adrenal glands (in 4 cases preview history of unilateral adrenalectomy), 55
      adrenal glands were correctly identified and evaluated. The only exception was
      the left adrenal gland of a patient with Billroth-II-stomach, which was slightly
      pulled to the right and very small. Healthy adrenal glands are slightly
      hyperechoic as compared to the parenchyma of the kidney and have echogeneity
      comparable to other endocrinal organs such as the testicles or the thyroid.
      Endosonographic imaging of the adrenal glands is far superior in resolution and
      determination to transabdominal sonography. In 18 of 30 patients (60%)
      endosonography provided additional diagnostic information compared to
      conventional sonography. CONCLUSION: Endosonography of the adrenal glands enables
      imaging of these organs with high resolution using a 7.5 MHz transducer from a
      distance of 1-2 cm.

PMID- 9577887
TI  - [Diagnostic and prognostic value of vascular resistance in breast tumors].
AB  - AIM AND METHOD: In a prospective study of 113 patients with breast tumours, we
      measured the vascular resistance index (mean RI) of physiologic tissue and the
      tumour by using pulsed colour coded Doppler sonography. RESULTS: The group of
      carcinomas showed a significantly higher mean RI (0.71 +/- 0.09 SD) compared to
      the group of benign tumours (0.66 +/- 0.09 SD) (p = 0.003). After dividing the
      groups according to menopausal status, this difference disappeared. In general
      the mean RI was higher in postmenopausal women. Only premenopausal women showed a
      significantly higher mean RI within the carcinoma (0.69 +/- 0.1 SD) compared to
      physiological tissue (0.65 +/- 0.07 SD, p = 0.02). The mean RI measured in the
      tumour area from carcinomas correlated with the S-phase fraction: r = -0.53 (p =
      0.003). CONCLUSION: Mean RI reflects vascular resistance but does not allow
      discrimination between benign or malignant and is significantly influenced by
      menopausal status. The dynamics of proliferation and low vascular resistance seem
      to depend on each other. All these facts should be considered when doing Doppler
      sonographic examination of the breast.

PMID- 9577888
TI  - [Early detection of atherosclerosis with high resolution ultrasound exemplified
      by type II diabetic patients].
AB  - AIM: Endothelial Dysfunction (ED) is an early functional marker and Intima-Media
      Thickness (IMT) an early morphological parameter of atherogenesis. Is there a
      simple, non-invasive routine method for the identification of atherosclerosis
      including the detection of the early functional endothelial impairment seen for
      example in Type 2 diabetic patients? METHODS: Using high resolution ultrasound we
      studied peripheral endothelial function expressed as flow-associated dilation
      (FAD %) and endothelial independent vasodilation after administration of 400
      micrograms glycerol trinitrate (postnitro %) of the brachial artery as well as
      IMT of the common carotid artery in 25 Type 2 diabetic patients and their matched
      controls. RESULTS: (mean +/- SD): The diabetic patients showed a remarkable ED
      (FAD%: 3.8 +/- 3.3 vs. 6.9 +/- 4.4%, p = 0.01) and an already increased IMT (0.72
      +/- 0.14 vs. 0.62 +/- 0.10 mm, p < 0.01). The similar postnitro % in diabetic
      patients and controls suggests normal dilating capacity of the studied vessels in
      the diabetic patients (postnitro %: 14.3 +/- 9.4 vs. 14.9 +/- 8.5%, p = ns).
      CONCLUSION: With a combination of these three sonomorphological parameters it is
      possible to document the stage of atherosclerosis including endothelial
      dysfunction in Type 2 diabetic patients.

PMID- 9577889
TI  - [Value of color-coded duplex ultrasound in evaluating arm blood vessels--arteries
      and hemodialysis shunts].
AB  - AIM: Comparison of colour coded duplex sonography (CCDS) to angiography in
      visualizing arteries and haemodialysis fistulas of the upper extremity. METHOD:
      1145 arterial and vein segments were visualised using CCDS and angiography in 219
      patients by different examiners with different degrees of experience.
      Sensitivity, specificity and accuracy were calculated. RESULTS: For the arterial
      segments--subclavian artery up to the distal lower arm arteries--the sensitivity
      was 90% and the specificity 99%. The sensitivity for the detection of vascular
      alterations in haemodialysis fistulas was 89% and the specificity 95%.
      CONCLUSION: CCDS may be able to replace diagnostic angiography of the arm except
      when evaluating the hand arteries and the central veins.

PMID- 9577890
TI  - [3-dimensional ultrasound in clinical diagnosis of meniscus lesions].
AB  - AIM: To compare the significance of the two-dimensional and three-dimensional
      sonography in the diagnosis of meniscal tears under clinical conditions. METHODS:
      Sixty menisci of knees with clinical symptoms (44 medial and 16 lateral menisci)
      were examined by an identical transducer in a two- and three-dimensional
      sonography technique. The findings were compared with the diagnosis made with
      subsequent arthroscopy. RESULTS: In the diagnosis of meniscal lesions the two-
      and three-dimensional sonography reached a sensitivity of 92% and 100% and a
      specificity of 83% and 88%, respectively. The positive predictive value of these
      methods was 58% and 67%. The negative predictive value was 98% and 100%. Because
      of the good results with the two-dimensional sonography, there were no
      statistically significant differences between both methods. The three-dimensional
      sonography, however, proved to be superior, to the two-dimensional sonography in
      the analysis of subgroups (medial and lateral menisci, menisci with and without
      clinical symptoms). The negative predictive value of the three-dimensional
      sonography was 100% for all of these subgroups. CONCLUSION: Although this study
      shows no significant difference in the results of two- and three-dimensional
      sonography, the analysis of subgroups displays a slightly improved significance
      for diagnosis of meniscal tears by three-dimensional sonography. The high
      negative predictive value shows that three-dimensional sonography, performed by
      an experienced examiner, may be useful to exclude meniscal tears. This result may
      help focus further cost-intensive or invasive examinations.

PMID- 9577891
TI  - [Standardized ultrasound examination of the ankle joint. Clarification of
      ultrasound standard image sections by corresponding MRI sections].
AB  - AIM: The sonographical examination of the ankle was demonstrated in five standard
      cross-sections presented by the DEGUM (German Society for the Development of
      Ultrasonography in the Locomotor Apparatus) and compared with corresponding MRI
      cross-sections. METHOD: The sonographical examination was done in a real-time
      method with an ultrasound unit Type Versa (Siemens, Erlangen, Germany) and with a
      linear transducer (frequency 7.5 Mhz). The MRI tomographies were taken in two
      planes with the unit Type Magnetom (Siemens, Erlangen, Germany) with a 1.5 Tesla
      head-coil in T1- and T2-weighted spin echo sequences. RESULTS: Focus on the
      ventral, lateral and dorsal region provided a good overview of the superior ankle
      joint and the periarticular soft tissues. CONCLUSION: Being a cross-sectional
      method, the sonographical examination of the ankle joint offers additional
      information with regard to pathological changes of the joint and the
      periarticular soft-tissues.

PMID- 9577892
TI  - [Does maternal obesity increase the risk of fetal abnormalities? Analysis of
      20,248 newborn infants of the Mainz Birth Register for detecting congenital
      abnormalities].
AB  - AIM: To investigate the risk of congenital malformations for newborn of obese
      women (BMI > or = 30) compared with women of average prepregnancy weight.
      METHODS: We performed a prospective, population-based case-control study of
      20,248 newborn born in the city of Mainz. A total of 1,451 infants (cases) with
      and 8,088 without congenital malformations (controls) were analysed. The relative
      risks of associations between obesity and malformations were calculated as odds
      ratios (OR) with 95% confidence intervals (CI). RESULTS: The prevalence of
      malformations in children of obese mothers is 11.1% and thus approximately 4%
      higher than those of the total study population. There is a significant odds
      ratio for major malformations (OR 1.3; KI 1.0-1.7). Statistically significant
      associations were calculated for malformations of the internal urogenital system
      (OR 1.7; 1.1-2.8), the eyes (OR 5.0; 1.3-20.0) and for orofacial clefts (OR 1.7;
      1.1-2.8). Among the specific malformations the highest associations occurred for
      encephalocele (OR 7.3; 1.1-50.6), common truncus arteriosus (OR 6.3; 1.6-24.8)
      and Potter sequence (OR 6.3; 1.6-24.8). Adjustment for confounding factors (e.g.
      maternal diabetes mellitus and age) did not change the odds ratios. CONCLUSIONS:
      Our data demonstrate that newborn of obese mothers are at an increased risk for
      malformations. An adequate prenatal examination of these pregnancies should
      include ultrasound screening by specially trained ultrasonographers in tertiary
      units (DEGUM II/DEGUM III) and serum alpha-fetoprotein measurements. Public
      health campaigns for prevention are advised.

PMID- 9577893
TI  - [Ultrasound vascular imaging with echo contrast media].

PMID- 9577894
TI  - [Adolescents in general medical practice--a management problem?].
AB  - Even though adolescents suffer from a variety of complains, they often do not
      consult a physician. After a high consultations rate during infancy and
      childhood, the rate dramatically decreases at the age of 10. During this period,
      it is typical that a decreasing number of consultations are influenced by parents
      while adolescents increasingly make their own decisions to consult a physician in
      case of illness. Also a change from pediatric care to other forms of primary care
      takes place in this age. It is argued that the decrease of consultation rates in
      adolescence is caused by difficulties in creating a confident social relationship
      between physicians and adolescents and by a lack of age-adequate medical
      services. Proposals for an improvement of adolescent health care are made at the
      end of the paper.

PMID- 9577895
TI  - [Sports medicine aspects in children and adolescents].
AB  - In opposite to adults, exercise and sports are natural elements in the life of
      children and adolescents. However, they gain new aspects in the modern
      achievement-oriented society. The competitive sports are moving more and more
      towards the children's and adolescents's age. Additionally, sport should be done
      early during live for prevention of civilization diseases later on. Finally,
      physical therapy gains growing importance in the therapy and rehabilitation of
      children and adolescents. As to strength, children are not just 'small adults'.
      In children, the physical capacity in the aerobic range is larger and in the
      anaerobic range is smaller than in adults. The question of trainability and
      talent, respectively, plays an important role in the competitive sport as well as
      in the consultation of children for their sport career. The danger of the child
      during sport is discussed from the view of internal and orthopedic medicine.
      Concepts of sports medical preventions are derived from this discussion. The
      question of sports with pre-existing diseases in children and adolescents is only
      marginally discussed.

PMID- 9577896
TI  - [Counseling and therapy of children and their families after suicide attempts].
AB  - The suicidal action of a child has to be seen as an attempt to draw attention of
      those around it to its hopeless conditions of life. Professional aid is required
      and has to include all those to whom the child relates. Not the question of cause
      and guilt has to be discussed but the perspective of living without the idea of
      suicide and the demands of support for achieving this aim.

PMID- 9577897
TI  - [Possibilities and limits of guidelines in medicine].
AB  - Clinical practice guidelines can be used to achieve optimal utilization of scarce
      resources for the medical management of defined patient groups. However, this
      does not mean that the total amount of resources allocated to these patient
      groups will be reduced automatically. Examples of different health economic
      consequences for guideline implementation will be discussed, especially with
      regards to the cost-effectiveness to therapy and to the total health care budget.
      The procedural steps for developing evidence-based practice guidelines are
      described and the cost for their development is estimated. For Germany, the
      amount of this cost is about 400,000 to 500,000 DM per practice guideline. The
      development of evidence-based guidelines without accounting for cost
      effectiveness of therapy is not reasonable as cost-effectiveness is implied in
      the definition of guideline objectives. Practice guidelines that are not taking
      into consideration health economic data may diminish the cost-benefit relation of
      therapy. Quality criteria of sound evidence-based guidelines are introduced.
      Evidence-based guidelines that are developed in cooperation with recognized
      clinical experts attain wide acceptance among physicians. Sound evidence-based
      guidelines comprising cost-benefit relations of therapy can be the core of an
      internal health care reform.

PMID- 9577898
TI  - [Psychological concepts in pain therapy practice. 2: Behavior therapy, self
      management and overview of cognitive interventions].
AB  - In this part, the contribution of cognitive behavior therapy and the self
      management approach in psychological pain therapy is presented. A five-step-model
      of cognitive behavior is explained. The different steps are diagnostics,
      development of a new cognitive model of the disorder, acquisition of coping
      strategies, applications, transfer and relapse prevention. Focus of this paper
      are the coping strategies, thus, the interventions in confrontation with a pain
      stimulus. The self management approach has the goal to enable the patient to use
      coping strategies as quickly as possible by himself and to support the self
      regulation of the patient. At the end, a survey about cognitive self-control
      strategies is given.

PMID- 9577899
TI  - [Recommendations for the conversion of scientific information into practice
      relevant guidelines for emergency care in the city of Cologne. Conception of an 8
      step program].
AB  - Guidelines for prehospital emergency care within the chain of rescue are
      recommended. At the scene, information about the patient and therapeutical tools
      are limited. Accidents and emergencies happen outside of hospitals and doctor's
      offices, while environmental factors and logistic problems strongly determine the
      rescue process. The sequence of interventions or the choice of the right hospital
      with specific triage criterias are only examples for these problems. There is
      only limited scientific evidence for therapies performed prehospitally. However,
      scientific material for the preparation of guidelines should be evaluated by
      using standardized criteria. The rules of evidence based medicine according to
      Cook are a practical way to evaluate and classify scientific material and to
      establish practical guidelines. In this paper, an 8-step-program is introduced to
      develop practical guidelines for the Emergency Medical Services Cologne.

PMID- 9577900
TI  - [Structured documentation for quality management in patients with diabetes
      mellitus].
AB  - The medical services rendered by office-based physicians have to be assessed on
      the basis of valid, practicable, and reliable indicators. The necessity to
      implement such indicators follows from the fact that quality and economic
      efficiency have been combined. The indicators can be derived from already
      existing guidelines. The target is to define medical services according to their
      type, extent, frequency and their point of intervention with regard to the
      medical problems and the treatment goals. The aim is to implement measures that
      permit the qualitative and economic evaluation of medical services. On the basis
      of these indicators the Central Institute of Panel Physicians develops together
      with scientific groups data sets that are able to show if, and to which degree,
      physicians act guideline-conform. The data sets can be used as documentation
      modules for transmission purposes and will therefore be integrated into the
      standard interface for basic clinical data profiles of already existing practice
      computer systems. While the Centre of German Physicians for Quality Assurance in
      Medicine is responsible for guideline-development, the conversion of the
      guidelines into appropriate data set structures is accomplished by the Central
      Institute of Panel Physician. This close co-operation represents a useful
      division of the work to be done in connection with the implementation of quality
      management in physician offices.

PMID- 9577901
TI  - [Aspects of quality assurance in a rheumatology clinic. A contribution to the
      problem of length of stay and unnecessary admission].
AB  - In a rheumatological hospital, quality assurance has many aspects. Diagnostic as
      well as classification criteria are essential; however, they should not be
      regarded as a strait-jacket. The very important radiological diagnostics require
      optimal technology. All x-ray-pictures should only be interpreted by experienced
      rheumatologists. Also of importance is the documentation of all relevant data,
      sometimes for decades, especially the kind of drugs, their effectiveness and side
      effects and the assessment of activity, stage, progression and functional
      ability. Very important is also a close communication with other medical
      disciplines. Nursing in rheumatology is mostly underestimated quantitatively and
      qualitatively as well; it cannot be compared with nursing in other patients.
      Physical and occupational therapy are indispensable parts of treatment of in
      patients; under certain conditions, they may have priority in comparison to other
      treatments. For chronobiological reasons, physical therapy has a definite time
      requirement. A duration of 3 weeks is necessary to get therapeutically desired
      adaptation processes. Thus, the duration of stay in rheumatological departments
      must be longer than in other disciplines. An actual questionnaire, which has been
      sent to 50 rheumatological departments, asked the question, which reasons and
      indications will make future in-patient treatment necessary. As main reason, the
      comprehensive treatment options and induction of a special pharmacotherapy have
      been mentioned. Also an element of quality assurance in a rheumatological
      hospital is warmheartedness and humanity.

PMID- 9577902
TI  - [Process-oriented quality management in the hospital].
AB  - Procedures and experiences concerning the implementation of quality management in
      a midsize hospital with 6 medical disciplines are described. Quality of
      infrastructure was checked with lists and the quality of medical performance
      assessed by means of standardized numerical audit with all professional groups.
      Weaknesses were identified by comparing the result to each quality indicator with
      target standards. As examples, causal relations and consequences of deficiencies
      in clinical care documentation, scheme of preoperative diagnosis, co-ordination
      of surgical procedures and handling of complications are given in more detail.
      Obstacles were rated depending on frequency and risk potential, sometimes cost
      effectiveness. Members of all professional groups and departments involved
      participated in trouble solving teams to which external expert assistance was
      provided. For example, interventions leading to improved co-ordination of
      surgical activities and their impacts are specified. Improving systematically the
      quality of clinical procedures is one gateway to establish quality management in
      hospitals continuously and thoroughly becoming an integrated part of the
      corporate culture. Investment of resources is necessary but justified by midrange
      benefits.

PMID- 9577903
TI  - [Effect of proctocolectomy on fluid balance--comparison of conventional
      ileostomy, ileorectal anastomosis and ileoanal pouch operation].
AB  - Total colectomy for ulcerative colitis (UC) and familiar adenomatous polyposis
      coli (FAP) is mainly performed as an ileoanal Pouch procedure (IAP). Alternatives
      are ileorectal anastomosis (IRA) and conventional proctocolectomy with Brooke
      ileostomy (CPS). The different surgical techniques may influence the excretion of
      water and electrolytes in stool and urine and may lead to a higher risk for
      urolithiasis. We investigated patients (12 IAP, 12 IRA and 8 CPS) several years
      after surgery and compared them to twelve normal controls. Total fecal and
      urinary output was collected at two consecutive days. Volume and electrolytes
      were determined in stool and urine. The risk for urinary stone formation was
      calculated by nomograms. Fecal volume and sodium (Na+) excretion was increased in
      all therapy groups compared to controls. IAP and IRA had significant less stool
      volume and Na+ excretion compared to CPS. Augmented fecal Na+ excretion was
      compensated by reduction of renal output after colectomy compared to controls.
      There were no significant differences in the daily urine volume between any
      groups. There was no urolithiasis in any groups. The nomograms showed a risk for
      all groups and controls to develop urinary stones.

PMID- 9577904
TI  - Effect of different doses of erythromycin on colonic motility in patients with
      slow transit constipation.
AB  - BACKGROUND: Erythromycin has been proposed as a therapeutic agent for the
      treatment of functional motor disorders of the upper gastrointestinal tract.
      Moreover, some data exist showing a potential effect on colonic motility. AIMS:
      Since no data are available concerning erythromycin effects in chronically
      constipated patients, we investigated the effects of three different doses of the
      drug (50, 200, and 500 mg i. v.) on colonic intraluminal pressures in such
      patients. PATIENTS AND METHODS: 18 severely constipated women were studied by a
      colonoscopically-positioned manometric probe, and were randomized to receive one
      of three doses of erythromycin. Proximal and distal colonic motility was recorded
      basally, then during placebo infusion for 60 min and for a further 60 min after
      the drug had been infused. RESULTS: Analysis of the tracings showed that, except
      for the lowest dose in the distal colon, erythromycin failed to stimulate colonic
      motility in constipated patients. CONCLUSIONS: It is concluded that erythromycin
      cannot be considered a colokinetic agent, at least at doses commonly employed in
      the upper gut.

PMID- 9577905
TI  - [MRCP (magnetic resonance cholangiopancreatography)--an assessment of current
      status].
AB  - For the first time, magnetic resonance cholangiopancretography (MRCP) provides
      images of the biliary and pancreatic ducts based on 3D data similar to those we
      are used to from endoscopic retrograde cholangiopancreatography (ERCP) and
      percutaneous transhepatic cholangiography (PTC). Extraordinarily impressing is
      the fact that no contrast media have to be applied. The following manuscript
      shows technical basics and the development of this technique from gradient echo
      sequences to the recent single-shot techniques. Furthermore possibilities and
      limitations of MRCP will be discussed with respect to certain illnesses.

PMID- 9577906
TI  - [Interventional procedures of the bile duct in patients after stomach resections
      (Billroth II)].
AB  - In the hands of an experienced endoscopist ERCP is an important method for the
      diagnosis of biliopancreatic diseases of Billroth II patients, but less effective
      than in nonoperated patients. Percutaneous procedures increase the success rate
      of nonoperative therapy. We report our own results of in 386 Billroth II
      patients: Success rate of diagnostic ERCP was 73.6% (284/386). Interventional
      endoscopy was performed in 192 patients: Successful EST was carried out in 93.6%
      (160/171), and complete extraction of bile duct stones was achieved in 74.8%
      (107/143), sufficient bile drainage was achieved by placement of transpapillary
      endoprostheses in 96.3% (79/82), while successful PTCD and percutaneous therapy
      were performed in 21 cases. Technical problems result from a long afferent loop,
      the upside-down position in the duodenal stump and difficult bile duct anatomy.
      We observed a complications rate of 3.6% (14/386) and a mortality of 0.5%
      (2/386). Our results are comparable with those in the literature, in which a
      similar number of difficult patients are included.

PMID- 9577907
TI  - [A rare combination of pheochromocytoma ans somatostatin-rich neuroendocrine
      tumor of Vater's papilla (carcinoid) in a patient with von Recklinghausen
      neurofibromatosis].
AB  - A 74-year-old male suffering from Recklinghausen's fibromatosis (NvR) is
      reported. He presented with weight loss, cholestasis, endocrine and exocrine
      pancreatic insufficiency. These symptoms were caused by a neuroendocrine tumor of
      the ampulla of Vater containing somatostatin. The tumor induced an obstruction of
      both the common bile and the pancreatic duct. In addition to this uncommon tumor,
      a silent pheochromocytoma was found. The patient was treated by endoscopic
      papillotomy, substitution of pancreatic enzymes and additional enteral nutrition.
      After recovery no progression of the disease was observed over one year. A review
      of the literature shows that patients with neurofibromatosis are at high risk for
      periampullar tumors. In particular, somatostatin-rich carcinoids were previously
      documented. Pheochromocytomas are also quite prevalent in NvR. However the
      combination of NvR, pheochromocytoma and somatostatin-rich neuroendocrine tumors
      of the duodenum has only been reported a few times. An explanation for the high
      prevalence of neuroendocrine tumors in NvR might be the loss of neurofibromin, a
      tumor suppressor protein, which is the main product of the neurofibromatosis-l
      gene.

PMID- 9577908
TI  - Metastatic pancreatic VIPoma: deteriorating clinical course and successful
      treatment by liver transplantation.
AB  - Gastrointestinal neuroendocrine tumors are slowly growing and metastases are
      often limited to the liver. As a result of their favorable biological behavior
      these tumors have a relatively good prognosis even in metastatic stage. Due to a
      variety of therapeutic options patients with malignant neuroendocrine tumors may
      survive for extended periods of time up to ten years. Often a combination of
      different treatments and also alternation between the different therapeutic
      regimes is needed. A patient with excessive WDHA-syndrome and severe metabolic
      disturbances due to a pancreatic VIPoma with metastatic spread into the liver and
      abundant hormonal secretion is presented. Cytotoxic agents (streptozocin, 5
      fluorouracil and adriamycin) were able to alleviate clinical symptoms and to
      control tumor growth for six years. Analogues of somatostatin (octreotide) and
      interferon alpha had been very useful in controlling clinical symptoms and tumor
      progress for 18 months. Cytotoxic agents or octreotide were not able, however, to
      achieve any permanent cure. Eventually, treatment failure occurred with dramatic
      progression of symptoms and tumor growth, unresponsive to any medical therapy.
      Consequently, total hepatectomy and liver transplantation together with
      extirpation of the pancreatic primary tumor was performed and succeeded in
      providing a normal life to the patient. In our opinion the overall outcome of
      patients with metastatic VIPoma may be improved best by maintaining the patients
      on medical therapy until treatment failure occurs. In case of extended hepatic
      metastases orthotopic liver transplantation might be considered for patients with
      symptomatic disease who no longer respond to conventional treatment modalities.

PMID- 9577909
TI  - [Hepatopulmonary syndrome].
AB  - The hepatopulmonary syndrome (HPS) is a reversible pulmonary insufficiency in
      association with liver disease, most frequently liver cirrhosis. The pathogenesis
      of HPS is poorly understood. HPS is characterized by arterial hypoxemia caused by
      intrapulmonary arteriovenous shunts or marked vasodilatation of the pulmonary
      vessels and ventilation-perfusion mismatch in the absence of intrinsic heart or
      lung disease. Typical clinical signs are dyspnea in the upright position which
      improves in supine position (platypnoe) and decrease of arterial pO2 in the
      upright position (orthodeoxia). The diagnosis of HPS is based on clinical
      features, arterial blood gas analyses in supine and upright position, contrast
      echocardiography and lung perfusion scanning. Arteriovenous fistula can be
      excluded by pulmonary angiography. There is no established medical treatment of
      HPS. New medical and noninvasive therapies, such as transjugular intrahepatic
      Stent-shunt (TIPS), lead to improvement of HPS. These treatment modalities need
      further elucidation. HPS was shown to be reversible after orthotopic liver
      transplantation (OLTx) in some cases. Severe HPS, therefore, may be an indication
      rather than a contraindication for OLTx.

PMID- 9577910
TI  - [Endoscopic balloon dilatation versus endoscopic sphincterotomy for removal of
      bile duct calculi].

PMID- 9577911
TI  - [Blood oncogene detection in patients with colorectal carcinoma].

PMID- 9577912
TI  - [Collagen colitis, adenomatous polyp and colon carcinoma].

PMID- 9577913
TI  - [Lactose in drugs and lactose malabsorption].

PMID- 9577914
TI  - ["Genetization" of prenatal medicine].

PMID- 9577915
TI  - [Pre- and postnatal diagnosis and treatment of hydrops fetalis--an
      interdisciplinary problem].
AB  - Hydrops fetalis (HF) is diagnosed prenatally in one out of 600 pregnancies,
      thirty percent of these fetuses will die in utero. Post partum, one out of
      approximately 25,000 newborn infants is affected. With the introduction of Rhesus
      immunoprophylaxis only fifty percent of the cases with HF are caused by Rhesus
      hemolytic disease. There is a large variety of non-immunological reasons such as
      cardiac defects (hypoplastic left healt syndrome, atrio-ventricular canal),
      arrhythmias, cytomegalovirus- or parvovirus infection (9% HF), twin-to-twin
      transfusion syndrome (15-30% HF) or chromosomal abnormalities (28-45% HF).
      However, in one third of the non immunological cases of HF the etiology remains
      unclear. Early diagnosis by ultrasound scan faces both the obstetrician and the
      neonatologist with the problem of differential diagnosis as well as therapeutic
      options, respectively. Various diagnostic procedures such as fetal
      echocardiography, karyotyping, molecular genetic techniques and sophisticated
      serological testings will help to classify the etiology and to determine the pre-
      and postnatal management. Nevertheless, neonatal mortality still varies between
      50 and 95%.

PMID- 9577916
TI  - [Effect of interleukin 6 on uterine contractility in the human in vivo].
AB  - The influence on uterine contractility of inflammatory cytokines like interleukin
      6 is widely unknown. We were able to demonstrate in 16 human myometrial strips
      obtained during caesarean section in the organ chamber a highly significant (P <
      0.001) increase of the activity of uterine strips after addition of IL-6. This
      further emphasizes the importance of subclinical infections for the etiology of
      so called idiopathic preterm labour.

PMID- 9577917
TI  - [Appearance of inflammatory cytokines interleukin-1 beta and interleukin-6 in
      amniotic fluid during labor and in intrauterine pathogen colonization].
AB  - Subclinical intrauterine infections have been proposed to be one of the leading
      causes of preterm labor. The determination of inflammatory cytokines IL-1 beta
      and IL-6 in the amniotic fluid may be useful to identify women who have infection
      associated preterm labor. Amniotic fluid was collected from 99 women during
      amniocentesis, during cesarean section or at the time of amniotomy using sterile
      technique. IL-1 beta and IL-6 were determined by a specific ELISA. Fluid of each
      sample was cultured for aerobic and anaerobic bacteria and for Mycoplasma hominis
      and Ureaplasma urealyticum. Different populations were identified according to
      the criteria "gestational age", "active labor", "positive amniotic fluid
      cultures". Interleukin-6 was detectable in all samples of amniotic fluid. The
      second-trimester (weeks 14-27) amniotic fluid concentration of IL-6 (18-2270
      pg/ml) was higher than in the third trimester (weeks 28-42, 4-329 pg/ml). The
      difference was significant. Women in active labor had higher levels of IL-6 in
      their amniotic fluid than women not in labor (p < 0.01). There is no significant
      difference between women with preterm labor and delivery (weeks 28-37, 597-8670
      pg/ml) and with term labor and delivery (weeks 38-42, 24-8300 pg/ml). Only
      culture negative samples were included in this population. Interleukin-1 beta was
      not detectable in the majority (90%) of these samples. 30% of the women in labor
      had positive amniotic fluid cultures. The IL-6 concentration of this population
      was not elevated in comparison to women in labor with negative cultures.
      Interleukin-1 beta was present in high concentrations (5-1100 pg/ml) in all fluid
      samples with detectable bacteria. Our data suggest that IL-1 beta may indicate
      subclinical uterine infection. IL-6 is elevated in all fluid samples of women in
      active labor.

PMID- 9577918
TI  - [Effect of mode of delivery on early morbidity and mortality of premature infants
      (< or = 34th week of pregnancy)].
AB  - In a retrospective analysis (1985-1994) the influence of the mode of delivery on
      mortality and early morbidity of low birth weight infants (< or = 2500 gm and <
      or = 34 weeks of gestation) was assessed (n = 450). We only included cases that
      offered a choice between abdominal and vaginal delivery (cephalic and breech
      presentation, premature rupture of membranes and preterm labour). We found
      significantly higher survival rates in infants with birth weights of 1500 gm or
      less in case of breech and cephalic presentation after cesarean births. In
      infants with cephalic presentation and birth weights of 1500 gm or less no
      parameter of early morbidity was changed by the mode of delivery. Infants with
      breech presentation and birth weights of 1500 gm or less have less severe
      cerebral hemorrhages, cord pH values < or = 7.15 and have a lower incidence of
      primary intubation after abdominal delivery. Infants with birth weights of 1501
      2500 gm and cephalic presentation are better off after a vaginal delivery,
      because there is the same survival rate and some parameters of early morbidity
      (1' and 5' Apgar score, incidence of primary intubation) are better after
      spontaneous births. In breech infants with birth weights of 1501-2500 gm there
      are no differences in mortality and early morbidity after vaginal and abdominal
      birth. A logistic regression analysis showed, that the risk of dying was
      significantly higher in infants with cerebral hemorrhages (I degree-IV degrees)
      and in infants born before 1990. In infants with birth weights of 1500 gm or less
      the mortality rate was higher after vaginal delivery and in case of an 10' Apgar
      score <8. Regarding infants with birth weights of 1501-2500 gm the risk of dying
      was higher in infants that suffered from a respiratory distress syndrome I degree
      IV degrees and in case of birth weights of 2000 gm or less.

PMID- 9577919
TI  - [Persistent pulmonary hypertension in premature and newborn infants: selective
      pulmonary vasodilation with inhaled nitric oxide (iNO)].
AB  - Severe respiratory failure of the newborn often results in persistent pulmonary
      hypertension, which is characterized by increased pulmonary vascular resistance,
      decreased pulmonary blood flow and severe hypoxaemia. Since 3 years inhaled
      nitric oxide (iNO) has been used as a selective pulmonary vasodilator with
      variable success in the treatment of persistent pulmonary hypertension. In the
      present clinical pilot study 10 patients (4 newborns and 6 preterm infants)
      suffering from severe respiratory failure were treated with iNO. The aim of this
      study was to evaluate the effectiveness of inhaled NO and to discuss whether or
      not extracorporeal membrane oxygenation (ECMO) could be delayed or avoided. In
      all patients oxygenation improved without a decrease in systemic blood pressure.
      The median OI decreased from 41 to 16.5 during the first 4 hours of treatment and
      to 12 during the first 12 hours. One patient with congenital diaphragmatic hernia
      required ECMO therapy and died post operative. One preterm infant with primary
      pulmonary hypertension died during prolongated hypotension and hypoxemia. iNO may
      have reduced the need for ECMO which however should be available as an ultimate
      therapeutic option.

PMID- 9577920
TI  - [Sepsis and SIRS (systemic inflammatory response syndrome) in the puerperium-
      pathogenesis and clinical management].
AB  - PURPOSE: We report about 5 cases of "puerperal sepsis" to elucidate the clinical
      significance and resulting therapeutic management of Sepsis, SIRS (Systemic
      inflammatory response syndrome) and MODS (Multiple organ dysfunction syndrome),
      whose definitions were introduced at the Consensus Conference of the American
      College of Chest Physicians/Society of Critical Care Medicine in 1992. RESULTS:
      All patients had documented endomyometritis, 3 of them in combination with
      ovarian vein thrombosis. None of the patients responded adequately to
      conservative treatment with antibiotics and intravenously applied Heparin. After
      12 to 72 hours, because of clinical deterioration, all women underwent laparotomy
      with hysterectomy combined with an ovarectomy in 3 cases. Although the
      inflammatory "septic" source was removed by the surgical intervention, the
      clinical condition of 3 of the patients further deteriorated; they were suffering
      from SIRS, and 2 developed MODS. Symptoms of MODS were DIC, hypotension, kidney
      failure and encephalopathy. CONCLUSIONS: Our results support the theory that
      infection or trauma may initiate an endogenous inflammatory response which could
      progress to MODS even after removal of the initial source. Our findings, however,
      do not support the view that septic endomyometritis and postpartum ovarian vein
      thrombosis should be treated nonsurgically, because the clinical course in our
      patients was less complicated the earlier the surgical intervention was
      initiated.

PMID- 9577921
TI  - [Pregnancy-saving measures in premature rupture of fetal membranes in the 22nd
      week of pregnancy].
AB  - The obstetric-perinatologic problems raised by premature rupturing of the
      membranes in the 22nd gestational week is presented in the form of a case report
      from the Perinatal Centre of the University of Cologne. By close ultrasonic
      monitoring of the course of development, measurement of parameters of
      inflammation and administration of prophylactic antibiotics pregnancy could be
      prolonged by 9 weeks with good fetal outcome.

PMID- 9577922
TI  - [Induction of uterine contractions by Shigella].
AB  - The uterus-contracting properties of Shigellae in a clinically relevant dose of
      10(5) organisms per ml was investigated in 17 uterine strips which where
      dissected during caesarean section from the lower uterine segment. A highly
      significant (p < 0.001) increase in uterine activity was observed.

PMID- 9577923
TI  - [Screening for group B streptococci].

PMID- 9577924
TI  - [Symptomatic symphysis loosening/rupture in pregnancy].

PMID- 9577925
TI  - [Painful paresthesia after removal of the sural nerve for autologous nerve
      transplantation].
AB  - The sural nerve is the most common nerve serving as a donor in an autologeous
      nerve grafting procedure. However, there is a certain risk for the development of
      painful paraesthesias at the donor site. Patients in whom a short segment of the
      sural nerve was resected are suspected to have a greater risk. In a retrospective
      study we investigated the incidence of painful paraesthesias following removal of
      a segment of the sural nerve for a grafting procedure. The study includes 41
      patients, who were followed at least for one year after surgery (mean 30 months).
      9 patients (22%) complained of persisting painful paraesthesias at the donor site
      suggesting a neuroma at the proximal stump of the sural nerve. The comparison of
      the length of the nerve segment harvested for grafting shows a tendency for
      patients with shorter segments having a greater risk to develop painful
      paraesthesias. However, the difference between the two groups was statistically
      not significant.

PMID- 9577926
TI  - Short-term prognostic factors in lumbar disc surgery: the low back prognostic
      score is of predictive value.
AB  - In order to determine prognostic factors of lumbar disc surgery, we examined 107
      patients who were conventionally operated on in a prospective, consecutive study.
      We analysed general data, the case history, the neurological examination at
      admission and all data from imaging examinations and therapy. In addition, all
      patients received a questionnaire based on the Low Back Outcome Score [9, 10].
      The patients were re-examined after 2-8 months (103 days mean). According to
      their ratings on a pain grading scale, the patients were divided into a group
      with favorable and another with unfavorable results. These groups were analysed
      in relation to the patients' initial condition. At follow up, 88% of the patients
      had either completely recovered or their complaints had been relieved. According
      to the Low Back Outcome Score (LBOS), 64.5% went well. Used to evaluate the
      initial condition of the patients on admission the LBOS was able to predict
      favorable outcome in 68% and unfavorable outcome in 50%. To improve the
      prognostic value, we combined significant questions of the LBOS with the pain
      grading scale and significant prognostic factors to form a new prognostic score
      (Low Back Prognostic Score). With this new score we were able to predict a
      favorable outcome in 84% of our patients, and an unfavorable outcome in 71%. The
      Low Back Prognostic score seems to provide a sensitive method for predicting a
      favorable or unfavorable outcome for patients scheduled to undergo lumbar disc
      surgery.

PMID- 9577927
TI  - Neuronavigation--first experiences with three different commercially available
      systems.
AB  - Growing interest in neuronavigation also referred to as frameless stereotaxy has
      led to the development of various navigational devices employing different
      localization methods. In 152 procedures the authors have used neuronavigation.
      Cases included 89 intracranial- and 26 skull base tumours, 9 biopsies, 21
      vascular and 7 functional procedures on 144 patients since July 1993. In 75 cases
      the lesions were located in eloquent areas. In 82% (124) MRI, 13% (18) CT and 5%
      (8) both imaging methods were employed. Three neuronavigational devices with
      different localization methods were used for the procedures. The Viewing Wand
      (VW, ISG, Canada), a multijointed arm was used in 101 procedures. In 15 cases the
      SPOCS (Aesculap, Germany) consisting of cameras detecting infrared light from
      LED's mounted on instruments and in 51 cases the microscope-integrated MKM
      (ZEISS, Germany) was investigated, 15 times two systems were used simultaneously.
      Mean time necessary for preoperative registration was 23 +/- 13 min (VW), 21 +/-
      16 min (SPOCS) and 27 +/- 22 min (MKM) respectively. The mean accuracy of
      registration measured as RMS was 2.9 +/- 1.2 mm (VW), 3.3 +/- 0.9 mm (SPOCS) and
      3.1 +/- 1.0 (MKM) respectively. Regarding intraoperative handling the VW was
      found to be a robust but sometimes bulky and hindering device whereas the SPOCS
      was more flexible but with the need of unobstructed visibility between cameras
      and pointers. The MKM without these restrictions required training to get used to
      handling.

PMID- 9577928
TI  - Dorsal extradural lipoma as cause of spinal claudication. Case report and review
      of the literature.
AB  - Extradural spinal lipomas are rare tumorous lesions. "True adult lipomas" have to
      be histologically differentiated from angiolipomas. The authors describe a case
      of segmental dorsal lipomas in the lower lumbar spine which led to a clinical
      apparent spinal claudication. Having reviewed the literature this case is the
      first ever described. In this case MRI was the diagnostic tool of choice. The
      tumor could be removed completely via interarcual laminotomy and flavectomy. The
      clinical outcome was excellent. In differential diagnosis of a spinal
      claudication this rare cause should be kept in mind when typical osseous changes
      are absent.

PMID- 9577929
TI  - [Erwin Payr and his contributions to neurosurgery].
AB  - After having studied medicine in Vienna and worked in Graz, Greifswald and
      Konigsberg, Erwin Payr, born February 17, 1871 in Vienna, led the Department of
      Surgery for nearly twenty-five years at the University of Leipzig. Under his
      leadership a private surgical clinic was founded, the present-day Clinic for
      Neurosurgery at the University of Leipzig. His surgical innovations include,
      among others, a new technique in the draining of brain abscesses through the use
      of elderberry stem capillaries, in the employment of absorbable magnesium threads
      for vascular and nerve sutures, as well as in the anesthetizing of the trigeminal
      nerve second branch in the case of trigeminal neuralgia. During the First World
      War he dedicated himself above all to neurotraumatic subjects such as the
      diagnosis and therapy of cranial and brain traumas. The reduction of elevated
      intracranial pressure and the creation of a passage of the cerebral fluid through
      the ventricle drainage in cases of hydrocephaly represented central themes of
      Payr's scientific works in the field of neurosurgery. Erwin Payr, recipient of
      manifold honors for his scientific contributions, his service as Professor and
      his multifaceted surgical knowledge, died in Leipzig in 1946 at the age of 75.

PMID- 9577930
TI  - Thermally induced molecular disorder in human stratum corneum lipids compared
      with a model phospholipid system; FT-Raman spectroscopy.
AB  - The molecular basis of lipid packing in human stratum corneum and a model
      phospholipid system has been studied as a function of temperature using Fourier
      Transform (FT) Raman spectroscopy. Thermally induced molecular rearrangements of
      the model lipid system, dipalmitoylphosphatidyl choline (DPPC), and stratum
      corneum were investigated using FT Raman spectroscopy coupled to a heating
      chamber. Spectra were recorded for a range of sample temperatures and the results
      for the two systems were compared, producing previously unreported information of
      the thermal behaviour for the different systems. Discrete thermal events were
      recorded for both systems by plotting band separation of the lipid v(CH2)
      symmetric and asymmetric stretching modes against temperature. The main thermal
      events observed for DPPC included a 'pre-melting' between 37 and 39 degrees C,
      the main transition observed between 41 and 42 degrees C, a 'post-transition'
      between 42 and 43 degrees C and three minor transitions at 58-60, 65-70 and 75-80
      degrees C. No evidence was found for the pre-transition of DPPC, previously
      observed at 34-35 degrees C. The main transitions for human stratum corneum were
      observed at 35-45, 55, 72 and 83 degrees C, measured from lipid CH2 stretching
      and bending vibrations. The keratin thermal transition at about 100 degrees C
      exerted little effect on the lipid bands and no characterisable structural
      changes were reflected in the keratotic bands.

PMID- 9577931
TI  - Study of human neurovegetative and hematologic effects of environmental low
      frequency (50-Hz) electromagnetic fields produced by transformers.
AB  - A survey of neurovegetative and hematologic disorders was conducted in a
      population (n = 13) exposed occupationally to environmental electromagnetic
      fields; the population was matched with 13 control subjects. The exposed subjects
      worked at least 8 h/d for 1-5 y in premises located above transformers and high
      tension cables, and the subjects were submitted to low-frequency electromagnetic
      fields (i.e., 50 Hz) of 0.2 microT-6.6 microT. The subjects were matched with
      respect to socioeconomic category, sex, and age with a control population of
      subjects that worked in premises outside of the immediate vicinity of
      transformers or high-tension cables. The exposed population had a significant
      increase in degree of certain neurovegetative disorders (i.e., physical fatigue,
      psychical asthenia, lipothymia, decreased libido, melancholy, depressive
      tendency, and irritability). In addition, the population experienced a
      significant fall in total lymphocytes and CD4, CD3, and CD2 lymphocytes, as well
      as a rise in NK cells. Leukopenia and neutropenia were also observed in two
      persons permanently exposed to doses of 1.2-6.6 microT. The disorders disappeared
      when exposure stopped, and they reappeared on reexposure.

PMID- 9577932
TI  - Exposure of workers to 2,3,7,8-substituted polychlorinated dibenzo-p-dioxin
      (PCDD) and dibenzofuran (PCDF) compounds in sawmills previously using
      chlorophenol-containing antistain agents.
AB  - The use of chlorophenol-containing antistain agents (e.g., Ky5, a wood
      preservative) ceased in Finland at the end of the 1980s, after 5 decades of use.
      Exposure of workers to the impurities in these agents (i.e., polychlorinated
      dibenzo-p-dioxins [PCDDs] and dibenzofurans [PCDFs]) was assessed at three
      sawmills at which personnel used a sodium chlorophenate product as an antistain
      agent. Given that compounds accumulate in body fat and their half-lives in humans
      are long, we could determine 2,3,7,8-substituted PCDDs and PCDFs 5-9 y after the
      last exposure occurred. We used high-resolution gas chromatography/high
      resolution mass spectrometry to determine PCDDs/PCDFs in plasma from 39 Ky5
      exposed workers and 18 nonexposed workers. The average total plasma concentration
      of PCDD/PCDF of the Ky5-exposed workers at the three sawmills were 1018, 945, and
      1165 pg/g fat, and corresponding concentrations in the nonexposed workers were
      743, 1124, and 844 pg/g fat, respectively. We found no significant differences in
      total levels between Ky5-exposed workers and nonexposed workers. However,
      concentrations of the 1,2,3,4,6,7,8-HpCDF isomer were significantly higher (p <
      .01) among the Ky5-exposed workers at all three sawmills (averages of 224, 99,
      and 148 pg/g fat) than among their respective nonexposed workers (averages of 43,
      48, and 44 pg/g fat). These results indicate that workers had handled Ky5. When
      we expressed concentration levels in international toxic equivalents (I-TEQs),
      the mean total I-TEQ PCDD/PCDF of Ky5-exposed workers was significantly lower at
      one of the sawmills (average = 42 pg I-TEQ/g) than at the other two sawmills
      (averages of 64 and 62 pg I-TEQ/g)(p < .05). Nevertheless, total concentrations
      at the sawmills studied were within the range of background levels in the general
      population.

PMID- 9577933
TI  - Descriptive study of deaths from cancer associated with residential proximity to
      the site of underground nuclear detonations.
AB  - During the 1960s, two nuclear detonations were exploded in an underground salt
      dome in Lamar County, Mississippi. Citizens in this rural area expressed concern
      about excess cancer among the residents as a result of exposure to tritium.
      Researchers initiated an epidemiologic investigation in response to these
      concerns. Investigators identified 2251 deaths, of which 562 (25.7%) were cancer
      related. Observed cancer rates for the area of Mississippi were no different than
      those expected for the state as a whole. Investigators found no association
      between cancer mortality and distance from the center of detonation.

PMID- 9577934
TI  - Termite control and other determinants of high body burdens of cyclodiene
      insecticides.
AB  - Breast milk fat concentrations of three cyclodiene insecticides--dieldrin,
      heptachlor epoxide, and oxychlordane--were measured in 797 primiparous women, and
      sources of exposure that contributed significantly to high body burdens were
      investigated. All three distributions were highly skewed to the right, with
      median concentrations falling between 0.007 and 0.039 mg/kg. Termite control of
      residence was associated consistently with being in the high-body-burden group
      for all three compounds, but the association was greatest for heptachlor. Age,
      socioeconomic status, residential area, smoking, and home use of insecticides
      were also associated with high body burden of one or more of the compounds, but
      the odds ratios were lower than those for termite control; the findings were
      inconsistent for the three compounds. The results for termite control remained
      statistically significant when we adjusted for the other factors; therefore,
      termite control of residence is an important risk factor for cyclodiene
      insecticide absorption.

PMID- 9577935
TI  - Personal exposure to nitrogen dioxide pollution and effect on plasma
      antioxidants.
AB  - We conducted a cross-sectional epidemiological study to evaluate personal
      exposure to nitrogen dioxide and its effect on blood antioxidants. Personal
      exposure of 107 volunteers was assessed for 14 d with passive monitors. We
      excluded heavy smokers (> 10 cigarettes/d) from the study. Sociodemographic and
      environmental data, as well as beta-carotene intake, were recorded. We mainly
      attributed the mean nitrogen dioxide personal exposure (31.9 +/- 12.7 microg/m3
      [0.017 ppm or 0.70 microM/m3]) (R2 = 0.75) to residence site in the city, time
      spent in urban traffic, and use of gas stoves. The correlation between nitrogen
      dioxide exposure and blood antioxidant concentration was weak; in addition, the
      correlation coefficients for men and women were inconsistent. Nonetheless, we
      found some evidence of an interaction between carotene intake and nitrogen
      dioxide exposure: a significantly lower plasma beta-carotene level was evident
      among subjects who consumed < or = 4.5 mg/jour of carotene and who were exposed
      to nitrogen dioxide levels that exceeded 40 microg/m3 (0.021 ppm or 0.87
      microM/m3) of nitrogen dioxide.

PMID- 9577936
TI  - Increased mercury exposure in inhabitants living in the vicinity of a hazardous
      waste incinerator: a 10-year follow-up.
AB  - A hazardous-waste-treatment plant that housed an incinerator began operation in
      1984, before which a baseline survey of the surrounding population and
      environment was conducted; 10 y later, investigators studied the same subjects.
      Researchers focused on mercury exposure because mercury concentrations were
      present in the stack emissions, and environmental monitoring revealed mercury
      concentrations near the plant. In 1984 and 1994 the median hair mercury
      concentrations were 0.5 mg/kg and 0.8 mg/kg, respectively. During the 10-y
      period, median hair total mercury concentrations increased by 0.35 mg/kg in
      workers (n = 11); by 0.16 mg/kg, 0.13 mg/kg, and 0.03 mg/kg in individuals who
      lived 2 km (n = 45), 2-4 km (n = 38), and 5 km (n = 30) from the plant,
      respectively; and by 0.02 mg/kg in the reference group (n = 55). In summary,
      mercury exposure increased as distance from the plant decreased; however, the
      increase in exposure was minimal and, on the basis of current knowledge, did not
      pose a health risk.

PMID- 9577937
TI  - Acute toxic effects of fragrance products.
AB  - To evaluate whether fragrance products can produce acute toxic effects in
      mammals, we allowed groups of male Swiss-Webster mice to breathe the emissions of
      five commercial colognes or toilet water for 1 h. We used the ASTM-E-981 test
      method to evaluate sensory irritation and pulmonary irritation. We used a
      computerized version of this test to measure the duration of the break at the end
      of inspiration and the duration of the pause at the end of expiration. Decreases
      in expiratory flow velocity indicated airflow limitation. We subjected the mice
      to a functional observational battery to probe for changes in nervous system
      function. The emissions of these fragrance products caused various combinations
      of sensory irritation, pulmonary irritation, decreases in expiratory airflow
      velocity, as well as alterations of the functional observational battery
      indicative of neurotoxicity. Neurotoxicity was more severe after mice were
      repeatedly exposed to the fragrance products. Evaluation of one of the test
      atmospheres with gas chromatography/mass spectrometry revealed the presence of
      chemicals for which irritant and neurotoxic properties had been documented
      previously. In summary, some fragrance products emitted chemicals that caused a
      variety of acute toxicities in mice.

PMID- 9577938
TI  - Some dietary predictors of plasma organochlorine concentrations in an elderly
      German population.
AB  - Associations between reported consumption of animal products and chlorinated
      hydrocarbon concentrations were examined in 297 elderly people who lived in
      Germany. Consumption of beef and lamb was correlated positively with
      hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), total
      polychlorinated biphenyls (PCBs), and total dichloro-diphenyl-trichloroethane
      (DDT) (r = .13-.19, p < .05). Consumption of saltwater fish was correlated
      positively with alpha-HCH, dieldrin, and PCBs (r = .12-.26, p < .05). Other
      univariate predictors were body mass index, plasma cholesterol, pork consumption,
      poultry consumption, and age. Multivariate linear models of predictors of each
      chlorinated species were constructed, and some form of meat was used as the main
      predictor; the sum of all meats (exclusive of fish) was the best predictor of
      dieldrin and In(alpha-HCH) concentrations. Beef and lamb consumption was a
      positive predictor of HCB, heptachlor epoxide, total DDT, and beta-HCH. Saltwater
      fish was the major dietary predictor of PCBs.

PMID- 9577939
TI  - Tobacco smoking and alcohol and drug consumption in a large, young healthy
      population.
AB  - The relationships between tobacco smoking and both alcohol and drug consumption
      were investigated in 2 431 healthy individuals aged 18-29 y. We used a
      questionnaire to evaluate smoking habits and alcohol and drug intake, and these
      parameters (i.e., cotinine-to-creatinine concentration ratio, amphetamines,
      cannabinoids, opiates, and cocaine) were quantified via urine analyses. Urinary
      cotinine concentration was significantly higher in current smokers (mean +/-
      standard deviation: 717 +/- 61 ng/mg creatinine, n = 881) than in non- or
      exsmokers (32 +/- 16 ng/mg creatinine, n = 1550). Information gleaned from the
      questionnaires revealed that there was a greater proportion of current smokers
      among consumers of alcohol than among nonconsumers. Significantly (p < .001) more
      current smokers than non- or exsmokers self-reported that they consumed
      sedatives, stimulants, or illegal drugs. Urinary cotinine concentrations were
      highest in consumers of alcohol and in self-reported consumers of sedatives (p <
      .0001), stimulants (p = .01), and illegal drugs (p < .0001). We found higher
      urinary cotinine concentrations in subjects who had positive urinary
      amphetamines, cannabinoids, or opiates. Even though the prevalence of alcohol and
      drug consumption remained low in the population we studied, such behaviors were
      clearly related to tobacco smoking.

PMID- 9577940
TI  - A respiratory ozone analyzer optimized for high resolution and swift dynamic
      response during exercise conditions.
AB  - The breath-to-breath determination of total respiratory ozone (O3) uptake
      requires the monitoring of O3 concentration at the airway opening with an
      instrument that responds rapidly relative to the frequency of respiration.
      Originally, the authors developed an analyzer that used the homogeneous
      chemiluminescent reaction of O3 with 2-methyl-2-butene, but it was suitable only
      for monitoring O3 during quiet breathing and light exercise (Ben-Jebria and
      Ultman, Rev Sci Instrum 1989; 60:3004-11, and Ben-Jebria et al., Rev Sci Instrum
      1990; 61:3435-39). The improvement of performance characteristics of the
      aforementioned analyzer enabled the authors to use the newly constructed and self
      contained instrument, which used ethylene as the reactant gas, for respiratory O3
      monitoring during moderate-to-heavy exercise. Operating at a reaction chamber
      pressure of 350 torr, an ethylene/sample flow ratio of 4:1, and a sampling flow
      of 0.6 lpm, the authors achieved an optimum analyzer performance (i.e., 10-90%
      step-response of 70 msec and a minimum resolution of 0.006 ppm O3). Furthermore,
      the new instrument did not exhibit the nonlinear calibration and the CO2
      interference suffered by the original analyzer. To demonstrate the quality of the
      new O3 analyzer in a respiratory application (i.e., total O3 uptake), the authors
      measured a series of single breaths on two subjects who breathed 0.11 and 0.43
      ppm O3-in-air mixtures for 15 min during rest, and during moderate and heavy
      exercise.

PMID- 9577941
TI  - The surgeon general: David Satcher, MD, PhD.

PMID- 9577942
TI  - Remembering Louis N. Katz, MD (1897-1973).

PMID- 9577943
TI  - Tumor necrosis factor-alpha and cardiomyopathy.

PMID- 9577944
TI  - Effects of cardiac versus circulatory angiotensin-converting enzyme inhibition on
      left ventricular diastolic function and coronary blood flow in hypertrophic
      obstructive cardiomyopathy.
AB  - BACKGROUND: Left ventricular (LV) diastolic function and coronary flow are
      impaired in hypertrophic obstructive cardiomyopathy (HOCM). This study was
      designed to evaluate the impact of cardiac and circulatory ACE inhibition on such
      derangements. METHODS AND RESULTS: Twenty patients with HOCM underwent cardiac
      ACE inhibition with intracoronary (IC) enalaprilat (0.05 mg/min infused into the
      left anterior descending coronary artery for 15 minutes) followed by circulatory
      ACE inhibition with 25 mg sublingual (SL) captopril. Contrast ventriculography,
      pressure, and coronary flow measurements were performed at baseline, after IC
      enalaprilat infusion, and 45 minutes after SL captopril. Heart rate was not
      affected by the respective interventions (75+/-11 versus 76+/-13 versus 75+/-10
      bpm; P=NS), whereas mean aortic pressure dropped slightly after IC enalaprilat
      and significantly after SL captopril (90+/-8 versus 85+/-10 versus 74+/-9 mm Hg;
      P<.05). Compared with baseline, IC enalaprilat resulted in a decrease in LV end
      diastolic pressure (17.6+/-5.9 versus 14.4+/-4.9 mm Hg; P<.05), time constant of
      isovolumic LV pressure relaxation (tauG) (69+/-9 versus 52+/-10 ms; P<.05), and
      outflow gradient (45.2+/-6.9 versus 24.4+/-3.7 mm Hg; P<.05) and in an increase
      in coronary blood flow (107+/-10 versus 127+/-12 mL/min; P<.05) and coronary flow
      reserve (2.2+/-0.4 versus 2.6+/-0.3; P<.05). After SL captopril, tauG was
      prolonged (60+/-13 ms; P<.05 versus IC enalaprilat), and LV outflow gradient,
      coronary blood flow, and coronary flow reserve values returned to baseline
      (45.5+/-5.3 mm Hg, 107+/-12 mL/min, and 2.2+/-0.5, respectively; P=NS versus
      baseline). CONCLUSIONS: Activation of the cardiac renin-angiotensin system
      contributes to LV diastolic dysfunction as well as to the decreased coronary
      blood flow and coronary flow reserve in HOCM. Cardiac ACE inhibition restores and
      circulatory ACE inhibition aggravates the above derangements.

PMID- 9577945
TI  - Reversal of abnormal coronary vasomotion by calcium antagonists in patients with
      hypercholesterolemia.
AB  - BACKGROUND: It has been shown that exercise-induced coronary vasodilation of
      angiographically normal coronary vessels is reduced in hypercholesterolemic
      patients. The purpose of this study was to evaluate the effect of calcium channel
      blockers on coronary vasomotion of angiographically smooth coronary arteries in
      hypercholesterolemic patients. METHODS AND RESULTS: A total of 57 patients were
      included in the present analysis. Vasomotion of angiographically normal coronary
      arteries was evaluated in 37 control subjects (group 1) without and 20 patients
      (group 2) with calcium blocker administration before physical exercise. Both
      groups were subdivided into subgroup A (normal cholesterol values: < or = 5.5
      mmol/L or 212 mg%) and subgroup B (elevated cholesterol values: >5.5 mmol/L or
      212 mg%). Coronary luminal area at rest and during exercise was assessed by
      biplane quantitative coronary angiography. The normal vessels showed a
      significant increase in coronary luminal area during exercise in subgroup A
      (n=13) with normal cholesterol values (31%; P<.05) but not in subgroup B (n=24;
      13%; P=NS). In contrast, all patients in group 2 showed similar vasodilation
      during exercise, namely, 22% (P<.05) in subgroups A (n=8) and B (n=12) (P<.05).
      Independent of the actual cholesterol level, the stenotic lesions showed coronary
      vasoconstriction during exercise in group 1 but vasodilation in group 2 after
      pretreatment with calcium antagonists. CONCLUSIONS: Coronary vasomotor response
      to exercise is inversely related to actual serum cholesterol level in
      angiographically normal vessels. Administration of calcium antagonists normalizes
      exercise-induced vasodilation and thus eliminates cholesterol-induced abnormal
      vasomotion, probably by a direct effect on the smooth muscles of the vasculature.

PMID- 9577946
TI  - Procedural results and late clinical outcomes after placement of three or more
      stents in single coronary lesions.
AB  - BACKGROUND: Previous reports have suggested higher procedural and long-term
      complications among patients treated with multiple stents for diffuse lesions
      and/or long dissections. METHODS AND RESULTS: To evaluate procedural success,
      major complications, and clinical outcomes (> or = 1 year) in a consecutive
      series of patients treated with multiple (> or = 3) contiguous stents in single
      lesions, we evaluated in-hospital and long-term (1-year) clinical outcomes in 117
      consecutive patients treated with > or = 3 coronary stents compared with a
      concurrent series of patients treated with 1 or 2 stents (n=1673) between January
      1, 1994, and December 31, 1995. Multiple stents were implanted more often in
      larger vessels, in the right coronary artery or saphenous vein grafts, and for
      unfavorable lesion characteristics, including long (>20 mm), calcified,
      ulcerated, thrombotic, and/or flow-obstructing lesions. Overall procedural
      success was obtained in 97.4% of patients and was similar whether 1 or 2 versus >
      or = 3 stents were used. Non-Q-wave MI (CK-MB > or = 5 times normal) was more
      frequent after > or = 3 stents (22.8% versus 13.4%, P=.005). Target lesion
      revascularization (TLR) was 14.6% for 1 or 2 stents and 13.3% for > or = 3 stents
      (P=.70). There was no difference in death (2.2% versus 0.9%, P=.34) or Q-wave MI
      (1.4% versus 0.9%, P=.64) between the two groups (1 or 2 stents versus > or = 3
      stents, respectively), and overall cardiac event-free survival was similar during
      follow-up (P=.70). CONCLUSIONS: Patients treated with multiple (> or = 3)
      contiguous stents compared with 1 or 2 stents have (1) similar in-hospital
      procedural success and major complications despite having more unfavorable lesion
      characteristics, (2) a higher rate of procedural non-Q-wave MI, and (3) similar
      TLR and overall major cardiac event rates during 1 year of follow-up.

PMID- 9577947
TI  - Comparison between noninvasive indices of baroreceptor sensitivity and the
      phenylephrine method in post-myocardial infarction patients.
AB  - BACKGROUND: Depressed baroreflex sensitivity obtained by means of a phenylephrine
      test plays a prognostic role in patients with a previous myocardial infarction.
      Our purpose was to evaluate the correlation and agreement between the baroreflex
      sensitivity obtained with phenylephrine and that obtained by two noninvasive
      methods: the alpha-index and sequence analysis. METHODS AND RESULTS: The alpha
      index was measured by means of the spectral analysis of RR and systolic blood
      pressure variabilities in both the high- and low-frequency bands; sequences were
      identified from simultaneously recorded time series in which the RR and systolic
      blood pressure concurrently increased or decreased. Noninvasive baroreflex
      sensitivity tests were performed during both spontaneous and controlled
      respiration. Fifty-two consecutive patients with recent myocardial infarction
      underwent the analyses. Although the correlations between phenylephrine and
      either of the noninvasive methods were always significant, those found during
      controlled respiration had the highest r values (r=.70). However, the limits of
      agreement calculated by means of the Bland and Altman method were wide for both
      noninvasive methods. CONCLUSIONS: The results obtained by means of noninvasive
      baroreflex sensitivity assessments should not be used in clinical practice as an
      alternative to those obtained by the phenylephrine method.

PMID- 9577948
TI  - Influence of type of surgery on the occurrence of parasympathetic reinnervation
      after cardiac transplantation.
AB  - BACKGROUND: Cardiac autonomic reinnervation after human cardiac transplantation
      has been demonstrated frequently but to date only for sympathetic efferents.
      Standard surgical techniques leave many parasympathetic branches intact in the
      original atria and thus with less stimulus to reinnervate the donor atria.
      METHODS AND RESULTS: We used changes in the RR-interval power spectrum induced by
      sinusoidal modulation of arterial baroreceptors by neck suction at different
      frequencies to detect both parasympathetic and sympathetic reinnervation in 79
      subjects with "standard" and 10 "bicaval" heart transplants. In 24 subjects (17
      standard and 7 bicaval), the protocol was repeated 6 and 11 months after
      transplantation. Neck suction at 0.20 Hz produced a component at 0.20 Hz in the
      RR-interval spectrum not due to respiration (fixed at 0.25 Hz), which suggested
      parasympathetic reinnervation, in 4 of 10 bicaval but in only 2 of 79 standard
      transplant subjects (whose recipient atria underwent >50% resection to remove
      scars of previous interventions), P<.001. In only 1 (bicaval) transplant subject
      was parasympathetic reinnervation present 6 months after transplantation
      (confirmed 3 months later); in 4 subjects, it was absent at 6 months but appeared
      after 11 months after transplantation. Atropine (0.04 mg/kg i.v.) abolished the
      response to fast (0.20 Hz) and reduced that to slow stimulation, confirming the
      presence of parasympathetic reinnervation (4 subjects). CONCLUSIONS:
      Parasympathetic reinnervation depends on the surgical technique: because bicaval
      surgery cuts all sympathetic and parasympathetic nerves, regeneration might be
      stimulated similarly in both branches. Standard surgery cuts only approximately
      50% of sympathetic fibers; most recipient parasympathetic axons remain intact,
      hence their regeneration might not be stimulated.

PMID- 9577949
TI  - Cardiac failure in transgenic mice with myocardial expression of tumor necrosis
      factor-alpha.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine
      that has been detected in several human cardiac-related conditions, including
      congestive heart failure and septic cardiomyopathy. In these conditions, the
      origin of TNF-alpha secretion is, at least in part, cardiac myocytes. METHODS AND
      RESULTS: To determine the consequences of TNF-alpha production by cardiac
      myocytes in vivo, we developed transgenic mice in which expression of a murine
      TNF-alpha coding sequence was driven by the murine alpha-myosin heavy chain
      promoter. Four transgenic founders developed an identical illness consisting of
      tachypnea, decreased activity, and hunched posture. In vivo, ECG-gated MRI of
      symptomatic transgenic mice documented a severe impairment of cardiac function
      evidenced by biventricular dilatation and depressed ejection fractions. All
      transgenic mice died prematurely. Pathological examination of affected animals
      revealed a globular dilated heart, bilateral pleural effusions, myocyte
      apoptosis, and transmural myocarditis in both the right and left ventricular free
      walls, septum, and atrial chambers. In all terminally ill animals, there was
      significant biventricular fibrosis and atrial thrombosis. CONCLUSIONS: This is
      the first report detailing the effects of tissue-specific production of TNF-alpha
      by cardiac myocytes in vivo. These findings indicate that production of TNF-alpha
      by cardiac myocytes is sufficient to cause severe cardiac disease and support a
      causal role for this cytokine in the pathogenesis of human cardiac disease.

PMID- 9577950
TI  - Pathophysiologically relevant concentrations of tumor necrosis factor-alpha
      promote progressive left ventricular dysfunction and remodeling in rats.
AB  - BACKGROUND: Although patients with heart failure express elevated circulating
      levels of tumor necrosis factor-alpha (TNF-alpha) in their peripheral
      circulation, the structural and functional effects of circulating levels of
      pathophysiologically relevant concentrations of TNF-alpha on the heart are not
      known. METHODS AND RESULTS: Osmotic infusion pumps containing either diluent or
      TNF-alpha were implanted into the peritoneal cavity of rats. The rate of TNF
      alpha infusion was titrated to obtain systemic levels of biologically active TNF
      alpha comparable to those reported in patients with heart failure (approximately
      80 to 100 U/mL), and the animals were examined serially for 15 days. Two
      dimensional echocardiography was used to assess changes in left ventricular (LV)
      structure (remodeling) and LV function. Video edge detection was used to assess
      isolated cell mechanics, and standard histological techniques were used to assess
      changes in the volume composition of LV cardiac myocytes and the extracellular
      matrix. The reversibility of cytokine-induced effects was determined either by
      removal of the osmotic infusion pumps on day 15 or by treatment of the animals
      with a soluble TNF-alpha antagonist (TNFR:Fc). The results of this study show
      that a continuous infusion of TNF-alpha led to a time-dependent depression in LV
      function, cardiac myocyte shortening, and LV dilation that were at least
      partially reversible by removal of the osmotic infusion pumps or treatment of the
      animals with TNFR:Fc. CONCLUSIONS: These studies suggest that
      pathophysiologically relevant concentrations of TNF-alpha are sufficient to mimic
      certain aspects of the phenotype observed in experimental and clinical models of
      heart failure.

PMID- 9577952
TI  - Locally propagated activation immediately after internal defibrillation.
AB  - BACKGROUND: Electrical mapping studies indicate an interval of 40 to 100 ms
      between a defibrillation shock and the earliest activation that propagates
      globally over the ventricles (globally propagated activation, GPA). This study
      determined whether activation occurs during this interval but propagates only
      locally before being blocked (locally propagated activation, LPA). METHODS AND
      RESULTS: In five anesthetized pigs, the heart was exposed and a 504-electrode
      sock with 4-mm interelectrode spacing was pulled over the ventricles. Ten
      biphasic shocks of a strength near the defibrillation threshold (DFT) were
      delivered via intracardiac catheter electrodes, and epicardial activation
      sequences were mapped before and after attempted defibrillation. Local activation
      was defined as dV/dt < or =-0.5 V/s. Postshock activation times and wave-front
      interaction patterns were determined with an animated display of dV/dt at each
      electrode in a computer representation of the ventricular epicardium. LPAs were
      observed after 40 of the 50 shocks. A total of 173 LPA regions were observed,
      each of which involved 2+/-2 (mean+/-SD) electrodes. LPAs were observed after
      both successful and failed shocks but occurred earlier (P<.0001) after failed
      (35+/-8 ms) than successful (41+/-16 ms) shocks, although the times at which the
      GPA appeared were not significantly different. On reaching the LPA region, the
      GPA front either propagated through it (n=135) or was blocked (n=38). The time
      from the onset of the LPA until the GPA front propagated to reach the LPA region
      was shorter (P<.01) when the GPA front was blocked (32+/-12 ms) than when it
      propagated through the LPA region (63+/-20 ms). CONCLUSIONS: LPAs exist after
      successful and failed shocks near the DFT. Thus, the time from the shock to the
      GPA is not totally electrically silent.

PMID- 9577951
TI  - Tumor necrosis factor-alpha confers resistance to hypoxic injury in the adult
      mammalian cardiac myocyte.
AB  - BACKGROUND: Previous studies in isolated cardiac myocytes have shown that tumor
      necrosis factor (TNF)-alpha provokes increased expression of 27- and 70-kD stress
      proteins as well as manganese superoxide dismutase, suggesting that TNF-alpha
      might play a role in mediating stress responses in the heart. METHODS AND
      RESULTS: To determine whether TNF-alpha stimulation would protect isolated
      cardiac myocytes against environmental stress, myocyte cultures were pretreated
      with TNF-alpha for 12 hours and then subjected to continuous hypoxic injury (O2
      content, 3 to 5 ppm) for 12 hours, followed by reoxygenation. Cell injury was
      assessed in terms of lactic dehydrogenase (LDH) release, 45Ca2+ uptake, and MTT
      metabolism. Pretreatment with TNF-alpha concentrations > or = 50 U/mL
      significantly attenuated LDH release by hypoxic cells compared with diluent
      treated hypoxic cells. Similar findings were observed with respect to 45Ca2+
      uptake and MTT metabolism in TNF-alpha-pretreated cells that were subjected to
      prolonged hypoxia. To determine the mechanism for the TNF-alpha-induced
      protective effect, the cells were pretreated with heat shock protein (HSP) 72
      antisense oligonucleotides. These studies showed that the protective effect of
      TNF-alpha was not inhibited by antisense oligonucleotides, despite use of a
      concentration of antisense that was sufficient to attenuate the TNF-alpha-induced
      increase in HSP 72 expression. Subsequent studies using mutated TNF ligands
      showed that activation of both types 1 and 2 TNF receptors was sufficient to
      confer a protective response in isolated cardiac myocytes through an as yet
      unknown pathway(s). CONCLUSIONS: Taken together, the above observations
      demonstrate that TNF-alpha pretreatment confers resistance to hypoxic stress in
      the adult cardiac myocyte through a novel mechanism that appears to be different
      from but not necessarily exclusive of the protective response conferred by HSP 72
      expression.

PMID- 9577953
TI  - Angiotensin-converting enzyme inhibitors.
AB  - ACE inhibitors have achieved widespread usage in the treatment of cardiovascular
      and renal disease. ACE inhibitors alter the balance between the vasoconstrictive,
      salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the
      vasodilatory and natriuretic properties of bradykinin and alter the metabolism of
      a number of other vasoactive substances. ACE inhibitors differ in the chemical
      structure of their active moieties, in potency, in bioavailability, in plasma
      half-life, in route of elimination, in their distribution and affinity for tissue
      bound ACE, and in whether they are administered as prodrugs. Thus, the side
      effects of ACE inhibitors can be divided into those that are class specific and
      those that relate to specific agents. ACE inhibitors decrease systemic vascular
      resistance without increasing heart rate and promote natriuresis. They have
      proved effective in the treatment of hypertension, they decrease mortality in
      congestive heart failure and left ventricular dysfunction after myocardial
      infarction, and they delay the progression of diabetic nephropathy. Ongoing
      studies will elucidate the effect of ACE inhibitors on cardiovascular mortality
      in essential hypertension, the role of ACE inhibitors in patients without
      ventricular dysfunction after myocardial infarction, and the role of ACE
      inhibitors compared with newly available angiotensin AT1 receptor antagonists.

PMID- 9577954
TI  - Images in cardiovascular medicine. Systemic embolism from a large ascending
      aortic thrombus.

PMID- 9577955
TI  - Images in cardiovascular medicine. Lipomatous hypertrophy of the atrial septum.

PMID- 9577956
TI  - Unfractionated heparin dosing in the FRIC study.

PMID- 9577957
TI  - How should we define inadequate coronary arterial remodeling?

PMID- 9577958
TI  - Factor V Leiden and thromboembolism.

PMID- 9577959
TI  - Sulfonylureas and cardiovascular mortality in diabetes: a class effect?

PMID- 9577960
TI  - Immunoreactivity of adventitial matrix fibrils of normal and aneurysmal abdominal
      aorta with antibodies against vitronectin and fibrinogen.
AB  - PURPOSE: We have reported that immunoglobulin G (IgG) harvested from specimens of
      aneurysmal abdominal aorta (AAA) is immunoreactive with a fibrillar component of
      the matrix of the aortic adventitia. In further studies we have reported the
      partial amino acid sequence of a 40-kDa protein, purified from the adventitia of
      the human aorta, which we have called aortic aneurysm antigenic protein-40 kDa
      (AAAP-40). AAAP-40 has homologies with bovine microfibril-associated glycoprotein
      36 kDa (MAGP-36). Both AAAP-40 and MAGP-36 have homologies to fibrinogen beta (FB
      b) and vitronectin (VN). The purposes of the present experiments were (1) to
      determine whether antibodies against VN and fibrinogen are immunoreactive with
      elements of the normal and/or aneurysmal aortic wall, and (2) to determine
      whether these antibodies are immunoreactive with soluble extracts of aortic
      proteins. METHODS: Paraffin-embedded tissue sections of normal and aneurysmal
      aorta were probed with polyclonal rabbit antihuman VN and antihuman FB-b
      antibodies. Immunoblots of soluble aortic proteins were evaluated with the same
      antibodies. Histochemical preparations with Gomori's aldehyde fuchsin and elastin
      von-Gieson solutions were also performed. RESULTS: Anti-VN and FB-b antibodies
      reacted with matrix fibrils in the aortic adventitia in both normal and
      aneurysmal specimens, with a distribution that resembles the appearance of
      fibrils that are stained by Gomori's reaction. By comparison to normal
      adventitial fibrils, fibrils in the specimens from AAA appeared fragmented,
      coiled, and frayed. Antibodies against VN and FB-b were immunoreactive in
      immunoblots with a soluble aortic protein of molecular weight approximately 40
      kDa, consistent with the migration of AAAP-40. CONCLUSIONS: There appear to be
      immunodeterminants in AAAP-40 that are recognized by polyclonal antibodies
      against VN and FB-b.

PMID- 9577962
TI  - Changes in antigen expression on B lymphocytes during HIV infection.
AB  - Involvement of the B cell compartment during HIV infection plays an important
      role in the development of immune deficiency. The aim of this study was the
      identification of specific antigen expression changes on B lymphocytes in HIV
      infection as surrogate markers in this cell population of certain functional
      aspects that could be easily measured. We investigated the level of expression of
      a series of constitutive surface markers in B lymphocytes (HLA-DR, CD19, CD20,
      CD21, CD22) from 30 HIV-seropositive adult patients and 20 normal controls. By
      means of quantitative flow cytometry, we assessed the number of antigen molecules
      per cell using standard beads to convert fluorescence intensity into antibody
      binding capacity (ABC). We correlated these results with disease stage and
      cellular markers of immune activation. The expression of CD20 was significantly
      increased when B cells from HIV-infected individuals were compared with those
      from uninfected subjects. No differences were found in the density expression of
      HLA-DR on activated CD3+ T cells between HIV+ and HIV- subjects. In contrast, B
      cells from HIV+ patients showed a significantly lower number of HLA-DR molecules
      per cell compared to normal controls. A significantly lower number of CD21
      molecules per cell was also found on B lymphocytes from HIV+ patients compared to
      normal controls. No differences in CD19 and CD22 expression levels on B cells
      between HIV-infected patients and controls were detected. No differences between
      HIV disease stages were detected for CD19, HLA-DR, CD21 and CD22. In contrast,
      differences between stages were found for CD20 expression, which showed
      significant changes in individuals with less than 200 CD4 T cells/microl. The
      data presented here demonstrate that B lymphocytes of HIV-infected individuals
      exhibit specific changes in receptor density expression during HIV infection and
      that these changes are often correlated with progression of disease, as measured
      by CD4 counts. No correlations were found between the percentages of HLA-DR+ T
      cells and the ABC values of the B cell markers studied. These antigen expression
      modulations may contribute to the humoral abnormalities during HIV infection and
      to the development of severe, recurrent or multiple bacterial infections.
      Therefore, quantitative flow cytometry may be of value in HIV infection both for
      clinical and biological studies. The study of antigen density changes on B cells
      in HIV infection may allow a better understanding of the humoral immune defects
      observed in these patients and provide insights into the functional defects of B
      cell compartment in HIV-infected individuals.

PMID- 9577961
TI  - 72-kD (MMP-2) and 92-kD (MMP-9) type IV collagenase production and activity in
      different histologic types of lung cancer cells.
AB  - In this study we examined the production of gelatinases A and B (MMP-2 and MMP
      9), and their natural inhibitors TIMP-1 and TIMP-2 in cell lines derived from
      different histologic types of lung cancer. Gelatinolytic activity was measured by
      zymography and radiolabeled gelatin degradation. Immunocytochemistry and Western
      blot analysis were performed to corroborate the presence of immunoreactive MMP-2,
      MMP-9, TIMP-1 and TIMP-2 proteins. The highest gelatinolytic activity was
      identified in the cell extracts from a small-cell carcinoma cell line. MMP-9 was
      observed in all samples as a proenzyme, while MMP-2 was present as zymogen in the
      squamous-cell and in the small-cell carcinomas, and in its active form in one
      squamous-cell carcinoma cell line. TIMPs were also present in the neoplastic lung
      cell lines. TIMP-1 was observed in the media of all cells as a 21-kD band, and as
      TIMP-1 polymers with the exception of the small-cell carcinoma samples. TIMP-2
      was found as higher-order molecular immunoreactive complexes that may correspond
      to proMMP-2/TIMP-2 complexes. These results demonstrate that lung neoplastic
      cells produce both MMP-2 and MMP-9 and their inhibitors, with the small-cell
      carcinoma cell extracts showing the highest enzymatic activity. This
      gelatinolytic activity fits well with the clinical metastatic behavior of this
      type of lung cancer.

PMID- 9577963
TI  - Differential regulation of the expression of cytokine-induced neutrophil
      chemoattractant by mouse macrophages.
AB  - The production of cytokine-induced neutrophil chemoattractant (CINC) by
      functionally diverse mouse bone-marrow-derived macrophages was determined.
      Studies showed that beta1,3-glucan, IL-beta, TNFalpha and IFNgamma/TNFalpha
      induced expression and production of CINC in macrophages while neither IFNgamma
      nor TGFbeta alone induced detectable CINC expression. Pretreatment or
      simultaneous treatment of macrophages with TGFbeta resulted in suppression of
      CINC protein production. These studies demonstrate that IFNgamma and TNFalpha,
      found early during the inflammatory response, induce production of CINC, as well
      as induce macrophages into a cytocidal state that are capable of killing
      transformed cells, parasites and bacteria, and recruiting neutrophils. In
      contrast, TGFbeta, found during reparative stages of the inflammatory response,
      suppressed production of CINC, while inducing the development of inflammatory
      macrophages that are capable of producing lysosomal enzymes, enhanced endocytosis
      and ingestion of particulate matter and function to scavenge debris, debride
      tissue and stimulate repair.

PMID- 9577964
TI  - Biological basis of the HLA-B8,DR3-associated progression of acquired immune
      deficiency syndrome.
AB  - The factors influencing the evolution of human immunodeficiency virus (HIV)
      infection are not fully known, but the host genotype undoubtedly plays a role in
      determining the outcome of the disease by affecting the immune response to HIV.
      The role of the host human leukocyte antigen (HLA) genotype in the regulation of
      susceptibility to HIV infection and expression has been studied extensively in
      different major risk groups. Certain HLA alleles and haplotypes, being associated
      with aberrant immune responses independently from HIV infection, have been
      reported to facilitate the rapid progression of disorders related to HIV
      infection. Particularly, the association of rapid acquired immunodeficiency
      syndrome (AIDS) progression with genes from the HLA-B8,DR3 haplotype has been
      reported by different research groups. It is well known that this haplotype is
      associated in all Caucasian populations with a wide variety of diseases with
      autoimmune features and in healthy subjects with a number of immune system
      dysfunctions, as a reduced production of T helper (Th)1 type cytokine. HIV
      infection may act on this genetic background triggering immunopathogenetic
      mechanisms leading to AIDS with a dominant Th2 profile as a common feature.

PMID- 9577965
TI  - Is mts1(S100A4) gene involved in the metastatic process modulated by gamma
      interferon?
AB  - This study investigates the involvement of mts1 (S100A4) in the metastatic
      process. We have evaluated the levels of mts1 gene in murine cancer cells
      following modulation of the metastatic ability. We report here that modulation of
      the expression of mts1 gene in cells derived from a breast murine adenocarcinoma
      (TS/A) did not correlate with metastatic ability either when pretreated in vitro
      with gamma-interferon (gamma-IFN) or following transfection with gamma-IFN gene.
      In another series of experiments we treated the cell lines B16-A and B78H1, both
      derived from B16 melanoma, with gamma-IFN. An increased expression of mts1 was
      found only in B16-A, but not B78H 1, correlated with a strong increase in
      metastatic activity of B16-A clone upon gamma-IFN treatment.

PMID- 9577966
TI  - Definition of early progenitors and functional maturation of human natural killer
      cells: requirements for cytocidal activity.
AB  - We examined the in vitro development of human natural killer (NK) cells to define
      the earliest hematopoietic progenitors which could give rise to NK cells. Our
      data indicates that NK cells arise from the Thy 1+ subpopulations of CD34+ marrow
      cells. In cultures with IL2 we generated up to 96.5% NK cells from CD34+ Thy 1+
      and in cultures with IL7, cells bearing NK cell surface markers were also
      observed but were devoid of functional activity. We also addressed the functional
      integrity of these cultured cells by examining the appearance of granzyme A,
      serine esterase, Met-ase and perforin and correlating these with lytic activity.
      Granzyme A mRNA could be detected in IL2-cultured cells and serine esterase
      activity as well as perforin were also found at the single cell level. Human Met
      ase (Hu-Met-1) was not detected at any time of analysis. Granzyme expression
      occurs early in cells cultured with IL2 but its presence did not correlate with
      lytic function; CD56+ cells grown in the presence of IL7 express these enzymes
      and perforin after longer periods of culture, but lack the ability to lyse NK
      targets.

PMID- 9577967
TI  - Massive proteinuria as a main manifestation of primary antiphospholipid syndrome.
AB  - Renal involvement in antiphospholipid syndrome (APS) is increasingly reported. So
      far, massive proteinuria as the principal feature of primary APS (PAPS) has not
      been well documented. We describe 3 patients with PAPS and massive proteinuria.
      Renal biopsy was performed in all 3, and features consistent with membranous and
      focal segmental glomerulopathy were disclosed. These histological lesions were
      not yet reported in PAPS. We conclude that the spectrum of renal lesions in PAPS
      is diverse and that it should be considered in the differential diagnosis of
      patients with massive proteinuria.

PMID- 9577968
TI  - Pediatric neurosurgery has the expertise and technology to cure many and insure
      independence for most children.

PMID- 9577969
TI  - Molecular biology of axonal outgrowth. 2. Pathfinding and molecular guidance
      cues.

PMID- 9577970
TI  - Functional opening of the fourth ventricular outlet in C57BL/6J and delayed
      splotch mouse embryos.
AB  - To compare the functional development of the fourth ventricular outlet in the
      myeloschisis-Chiari malformation complex with that of a normal brain, the
      chronological development of the outlet in C57BL/6J non-neural-tube defect mouse
      embryos was examined as the first step. Then we compared the results with those
      of homozygotic delayed splotch (Spd) mouse embryos which had neural-tube defects
      (NTDs). Ferrous chloride (Prussian blue) solution was injected into the lateral
      or mesencephalic ventricle on gestation days 13-16 in the case of control
      C57BL/6J mouse embryos and on gestation days 14-16 in the case of homozygotic Spd
      mouse embryos which had open spinal NTDs and hindbrain anomalies comparable to
      human Chiari malformation. At 30 min after the injection, acid fixative was
      infused through the heart to set off the Prussian blue reaction, which makes the
      dye visible by the precipitation of ferric chloride. According to the present
      method, more than 75% of C57BL/6J mouse (non-NTD control) embryos showed the
      evidence of function of the fourth ventricular (4V) outlet from gestation day 15.
      It was difficult to apply the same method to Spd mouse embryos with NTDs due to
      the small size of ventricles. Only 4 injections were successful, of which 3
      showed the functioning evidence of the 4V outlet. Though the number of mouse
      embryos with NTDs studied was small, the results suggest that the chronological
      progress of functional opening of the fourth ventricle in mouse embryos with NTDs
      is similar to that of control non-NTD embryos.

PMID- 9577971
TI  - Elevation of cerebrospinal fluid levels of basic fibroblast growth factor in
      moyamoya and central nervous system disorders.
AB  - Moyamoya syndrome is a vaso-occlusive disease involving the intracranial vessels
      of the circle of Willis which is accompanied by an intense compensatory
      recruitment of new vessels. Angiogenic substances such as basic fibroblast growth
      factor (bFGF) present in the cerebrospinal fluid (CSF) have been proposed as
      possible mediators of the neovascular response. We analyzed CSF samples collected
      intraoperatively from predominantly pediatric patients with moyamoya and other
      conditions such as Chiari malformation (Ch), tethered cord (TC), arteriovenous
      malformation (AVM), brain tumor (BT) and hydrocephalus (HCP). We found that CSF
      bFGF was significantly elevated in patients with moyamoya (141 pg/ml, n = 37), Ch
      (56.7 pg/ml, n = 22), TC (55.1 pg/ml, n = 23), AVM (354 pg/ml, n = 5), and BT
      (208 pg/ml, n = 5) compared to patients with HCP (5.5 pg/ml, n = 7) and controls
      (1.6 pg/ml, n = 25; p < 0.05). There was no dependence of CSF bFGF on patient age
      or gender. Although CSF bFGF in the moyamoya group showed no correlation with the
      Suzuki radiographic stage at either pre- or post-operative (1-year follow-up)
      angiography, it showed a trend with the Matsushima angiographic score with
      increasing collateral vascularization from the synangiosis developing at higher
      levels of CSF bFGF. Our findings suggest that CSF bFGF may be playing a wide
      ranging role in a number of central nervous system conditions associated with
      ischemia and hypervascularity. Although not a specific marker for moyamoya,
      elevated CSF bFGF may serve as a weak predictor of the extent of angiogenesis to
      be expected in indirect revascularization procedures.

PMID- 9577972
TI  - Quantitative analysis of the toxicity of human amniotic fluid to cultured rat
      spinal cord.
AB  - It has been proposed that the myelodysplastic components of a myelomeningocele
      are secondarily damaged as the result of exposure to amniotic fluid, the so
      called 'two-hit' hypothesis. The critical time at which this secondary insult
      might occur has not been clearly defined. The present study addresses this issue
      by quantitatively assessing the toxic effects of human amniotic fluid of various
      gestational ages upon organotypic cultures of rat spinal cord. Using an assay for
      lactate dehydrogenase efflux to evaluate toxicity in such spinal cord cultures,
      we found that the amniotic fluid became toxic at approximately 34 weeks'
      gestation. This toxic effect of amniotic fluid appears to emerge rather suddenly.
      Accordingly, it seems reasonable to suggest that prevention of exposure of
      vulnerable spinal cord tissue to this toxicity by surgical closure of a
      myelomeningocele defect prior to the emergence of toxicity in amniotic fluid may
      prevent injury to vulnerable myelodysplastic spinal cord tissue.

PMID- 9577973
TI  - Results and complications after reoperation for failed epilepsy surgery in
      children.
AB  - The seizure outcome and neurological outcome in children who undergo reoperation
      for failed epilepsy surgery have not been well documented. This retrospective
      study evaluated 20 children who underwent a second resective surgery for
      recurrent seizures. Four categories of patients were identified: (1) extension of
      the initial resection was performed in 8 patients; (2) 5 patients underwent
      lobectomy or corticectomy in a region remote from the original surgical site; (3)
      multilobar resection which may have included further resection of the initial
      procedure was accomplished in 4 patients; (4) hemispherectomy was performed in 3
      patients. Patients with reoperation in the same lobe as the first procedure
      (group 1) had a 62% seizure-free rate, while 44% of patients in groups 2 and 3
      were free from seizures at follow-up evaluation. Patients undergoing
      hemispherectomy had a 67% seizure-free rate. Significant unexpected neurological
      deficits occurred in 3 patients who underwent multilobar resection at
      reoperation. Complications included motor and language deficits. Reoperation for
      intractable partial epilepsy is beneficial in selected children. Patients who
      require multilobar resections may have higher risk of postoperative neurological
      deficit than those patients with reoperation in one lobe. These factors may be
      useful in counseling parents of children considering reoperation for recurrent
      epilepsy.

PMID- 9577975
TI  - Follow-up of children with shunted hydrocephalus.
AB  - In order to determine if routine yearly evaluations of children with shunted
      hydrocephalus were likely to diagnose shunt malfunction, we reviewed the medical
      records of the last 100 children who had such routine evaluations. Only 4
      children had symptoms that were potentially referable to malfunction; none were
      subsequently found to have malfunction and no child had signs of malfunction. We
      also reviewed the medical records of the last 100 children who had shunt
      revisions to determine if any of them were diagnosed during routine follow-up
      examinations. Four were: 2 with clinical signs of malfunction and 2 with evidence
      of malfunction on routine scans. Only 1 child in either group had signs or
      symptoms of malfunction if they had a functioning shunt in place for longer than
      1 year. Although yearly follow-up visits are common practice, we conclude that
      such examinations are unlikely to detect shunt malfunction. Follow-up at
      intervals of 2 years is probably appropriate after 2 years of age if the child
      has had a functional shunt for 1 year and has had a scan that indicates a
      functioning shunt.

PMID- 9577974
TI  - Clinical outcome of pediatric gangliogliomas: ninety-nine cases over 20 years.
AB  - Gangliogliomas account for 1-4% of all pediatric CNS tumors. We reviewed the
      records of 123 patients treated at the Children's Hospital of Philadelphia
      between 1974 and 1995. Ninety-nine patients were eligible for review with
      complete medical records. The mean age was 9.5 years with 52% females. The mean
      follow-up was 3.7 years. The most common presenting symptom was seizures (49%).
      The mean length of symptoms to diagnosis was 24.4 months. Complex partial seizure
      was the most frequent seizure type (60%). Electroencephalograms were abnormal in
      36%. The majority of gangliogliomas were in the temporal lobes (38%), with other
      sites in the parietal (30%) and frontal lobes (18%). All patients had abnormal
      nonspecific neuroimaging studies. Nine received chemotherapy, and 21 were treated
      with radiotherapy. Postoperatively, 78% were seizure free on no medication, 18%
      had improvement of seizure control, and 4% had stable seizure events. Nine died
      of disease. Gangliogliomas are benign tumors that frequently present with seizure
      disorders and nonspecific electroencephalographic and neuroimaging studies.
      Complete surgical extirpation of these tumors provides improved seizure control
      in most patients and a short course of antiepileptic medical therapy. Adjuvant
      therapy including radiotherapy and chemotherapy is limited to recurrent disease
      not amenable to reoperation.

PMID- 9577976
TI  - Visuvalve software: an aid to the diagnosis of shunt failure.
AB  - Software designed to help the neurosurgeon in the diagnosis of shunt malfunction
      is presented. This software allows the possibility to record on a 3.5 diskette a
      patient's clinical information and four views of a CT scan performed when the
      patient was doing perfectly well with his shunt. This diskette, operated by MS
      DOS on any IBM-compatible personal computer, can be read at any time, anywhere.
      The evaluation of the system demonstrated it was safe, with an excellent adhesion
      of the patients and of their families.

PMID- 9577977
TI  - Occipital encephalocele associated with mediastinal enteric duplication cyst.
AB  - Enteric duplication is a rare developmental anomaly. This anomaly can be seen
      anywhere along the gastrointestinal tract, and less than 2% of the cases extend
      to the mediastinum. Developmental neuroectodermal and cutaneous ectodermal
      abnormalities, especially vertebral midline fusion abnormalities, are frequently
      associated with enteric duplications. We report a case of a newborn with
      occipital encephalocele, also having a mediastinal enteric duplication cyst. The
      clinical course of this case is described in detail to emphasize the occurrence
      of life-threatening complications of these associated developmental abnormalities
      during the treatment of the primary pathology in the neurosurgery practice. In
      the literature, we failed to demonstrate any co-existence of these two
      developmental abnormalities and review the embryogenesis of the association of
      these congenital malformations presented here.

PMID- 9577979
TI  - Images in pediatric neurosurgery. Transtentorial herniation in 2-compartment
      hydrocephalus.

PMID- 9577978
TI  - Meningitis due to Ochrobactrum anthropi: an emerging nosocomial pathogen. A
      report of 3 cases.
AB  - We describe 3 cases of Ochrobactrum anthropi meningitis following the
      implantation of pericardial allograft tissue to cover dural defects following
      craniotomy. Following an extensive epidemiologic investigation, the tissue
      allograft was found to have been contaminated with this unusual organism during
      the harvesting and processing of the tissue in the tissue bank. This organism was
      only susceptible to imipenem, tetracycline, gentamicin, and ciprofloxacin. The
      clinical presentation of these patients was subacute. Two of the patients
      developed osteomyelitis of the bone flap; while another developed a relapse of
      infection along a former ventriculoperitoneal shunt track 6 months after the
      initial infection. Appropriate clinical outcome was only observed after removal
      of tissue allograft implants, debridement of devitalized tissue and bone, removal
      of shunt devices, and prolonged courses of antibiotics. No deaths were observed.

PMID- 9577980
TI  - Trends in caries prevalence in Dutch adults between 1983 and 1995.
AB  - In 1995, a dental survey was performed among adults aged 25-54 in the Dutch city
      of 's-Hertogenbosch. A similar study was performed in the same city in 1983 and
      the aim of the present study was to describe trends in oral health from 1983 to
      1995. National data show that the percentage of edentulous persons aged 30-39 and
      40-49 decreased from 11.3 to 3.3 and from 28.5 to 13.8, respectively, between
      1984 and 1993/94. The same trend was found in 's-Hertogenbosch. In persons with
      natural dentition under the age of 35 the mean number of DMFT decreased
      significantly between 1983 and 1995. In 1995 the mean number of FT was higher,
      and the mean numbers of DT and MT were lower than in 1983 in all age categories.
      It can be concluded that oral health in Dutch adults, as measured by caries
      prevalence, treatment level of caries and percentage of edentulous persons,
      improved significantly between 1983 and 1995.

PMID- 9577981
TI  - Five-year incidence of caries, salivary and microbial conditions in 60-, 70- and
      80-year-old Swedish individuals.
AB  - The 5-year incidence of dental caries in a random sample of 60-, 70- and 80-year
      old inhabitants of Goteborg was related to salivary and microbial conditions. Of
      the 208 persons examined at baseline, 148 (71%) participated in the follow-up
      examination; 69, 51 and 28, respectively, in the different age groups. The study
      revealed that 27% of the participants had not developed any carious lesions
      during the 5-year period and that the incidence of coronal and root caries
      increased with age. In the 60-year-olds, 2.5% of the susceptible coronal and root
      surfaces, respectively, had decayed, while the corresponding figures for the 80
      year-olds were 8.8% for coronal surfaces and 9.8% for root surfaces. In all, 18%
      had an unstimulated saliva secretion rate of below 0.1 ml/min and 14% had a
      stimulated secretion rate of <0.7 ml/min, with a mean rate which decreased with
      increasing age from 2.0 to 1.6 and 1.3 ml/min (p = 0.02). The overall salivary
      counts of lactobacilli and mutans streptococci, particularly the subspecies of
      Streptococcus sobrinus, had increased during the period. In the respective age
      groups of 60, 70 and 80 years, 15, 39 and 39% had a mutans streptococci count of
      > or = 10(6) CFU/ml in saliva and the corresponding figures for > or = 10(5)
      lactobacilli counts were 22, 31 and 43%. In the stepwise regression analysis, it
      was found that age, salivary levels of mutans streptococci and lactobacilli and
      number of teeth were the best predictors of the incidence of root caries. In
      conclusion, these observations indicate that there is an increased risk of dental
      caries with age owing to unfavourable microbial and salivary conditions.

PMID- 9577982
TI  - Prevalence and severity of dental caries in 12-year-old children in Kaunas,
      Lithuania 1995.
AB  - In order to evaluate suitable strategies for control of dental caries, a
      longitudinal study of caries progression has been initiated among 12-year-old
      children in Kaunas, Lithuania. The aim of the present paper was to describe the
      baseline caries situation in a sample of 12-year-olds, who had been examined
      using caries diagnostic criteria which differentiate between active and inactive
      caries lesions at both the cavitated and non-cavitated levels. The mean fluoride
      concentration in the drinking waters of Kaunas is 0.16 mg/l. A total of 889
      children in the 6th grade from seven selected schools were examined. Each tooth
      surface of all permanent teeth was classified according to one of the following
      criteria: 0 = sound; 1 = active, surface intact; 2 = active, surface
      discontinuity; 3 = active, cavity; 4 = inactive, surface intact; 5 = inactive,
      surface discontinuity; 6 = inactive, cavity; 7 = filled; 8 = filled with inactive
      lesion; 9 = filled with active lesion; X = extracted. Distinction between active
      and inactive lesions was made on the basis of a combination of visual and tactile
      criteria. Virtually all children (99.7%) had experienced at least 1 DMF surface.
      The mean DMFS was 15.8. Half of the mean caries experience consisted of surfaces
      with active lesions (7.9), of which two thirds (4.9) were non-cavitated. The mean
      number of surfaces with non-cavitated inactive lesions was 4.4. The mean DMFT
      constituted 7.9; 95% of all first molars were affected, followed by the second
      molars (61%). A comparison of the caries profile according to the present caries
      diagnostic criteria with those recommended by WHO revealed that the WHO criteria
      yielded much lower DMFS and DMFT values, because this scoring system does not
      include non-cavitated caries lesions. The high level of non-cavitated active
      caries lesions suggests that in this population caries may to a large extent be
      controlled by simple preventive measures including use of topical fluorides.

PMID- 9577983
TI  - Malnutrition and developmental defects of enamel in 2- to 6-year-old Saudi boys.
AB  - Three hundred and ninety boys aged 2, 4 or 6 years from Riyadh, Saudi Arabia,
      took part in a survey in 1993/94. The main aims of the study were first, to
      identify factors related to malnutrition in young children since a study of older
      children from the same area 1 year before had shown malnutrition to be strongly
      related to prevalence of developmental defects of enamel (DDE) of permanent teeth
      and, second, to identify factors related to the prevalence of developmental
      defects of primary teeth. Enamel defects were recorded by clinical examination of
      the buccal surfaces of all primary teeth by 1 examiner using the DDE index. A
      questionnaire to parents provided information on socio-economic status, illness
      in the mother and child, infant feeding, trauma to teeth and toothbrushing. A 24
      hour dietary record, to estimate water and milk intake, and a 24-hour urine
      collection were obtained for each child twice. Nutritional status was calculated
      from height for age using WHO methods. Multiple regression analyses revealed four
      variables related (p<0.05) to malnourished status: low birth-weight, low volume
      of water drunk, child stopped breast- and bottle-feeding before 1 year of age,
      and low class urban or rural area of residence. Birth-weight was itself related
      to area of residence (p = 0.02), parental education (p = 0.02) and maternal
      illness during pregnancy (p = 0.06). Malnutrition (p<0.001), low birth-weight
      (p<0.001), childhood illness (p<0.001), brushing of child's teeth (p = 0.003) and
      swallowing toothpaste (p<0.001) were related to the prevalence of developmental
      defects of primary teeth. This study indicated several independent variables
      which may be related to the prevalence of enamel defects in primary and permanent
      teeth, but longitudinal studies are required to determine which are causes and
      which are markers of these developmental defects.

PMID- 9577984
TI  - Identification of human serum albumin in human caries lesions of enamel: the role
      of putative inhibitors of remineralisation.
AB  - Carious attack on enamel is not a unidirectional process but involves both
      demineralisation and remineralisation. The chemistry of carious attack on enamel
      has, to a large extent, now been clarified as far as mineral components are
      concerned but little attention, however, has been paid to the identity of organic
      material in carious lesions and its possible role in the caries process. The only
      clear information available is that organic material accumulates with time within
      enamel lesions. The present study was aimed at identifying a specific protein
      component known to bind to hydroxyapatite (albumin) in carious lesions with a
      view to investigating its role in the disease process. The distribution of
      albumin within both white spot and fissure lesions and adjacent sound enamel of
      extracted human teeth was investigated using SEM immunohistochemistry on
      undermineralised sections of human enamel and employing a polyclonal antibody to
      human serum albumin. The nature of the protein, i.e. whether it was in the form
      of intact molecules or degraded fragments, was investigated by Western blotting,
      employing the same antibody. The immunohistochemistry revealed the presence of
      albumin within both interproximal white spot and fissure lesions with little if
      any present in sound enamel. The Western blotting indicated that the albumin was
      in the intact form with no evidence of degradation products. The ability of
      albumin to bind and to inhibit growth of calcium phosphate crystals raises the
      question as to the possible role of such a molecule in the development of carious
      lesions.

PMID- 9577986
TI  - Reliability of visual examination, fibre-optic transillumination, and bite-wing
      radiography, and reproducibility of direct visual examination following tooth
      separation for the identification of cavitated carious lesions in contacting
      approximal surfaces.
AB  - The aim of this study was to evaluate the diagnostic accuracy of visual,
      fibreoptic transillumination (FOTI), and bite-wing radiographic examination
      performed by 4 observers for the identification of cavitated carious lesions in
      contacting approximal surfaces, and to assess the inter-observer agreement with
      these methods and with direct visual examination conducted after tooth
      separation, the method used as validation for definitive determination of
      cavitation. A total of 338 unrestored approximal surfaces in 53 students were
      examined independently by 4 dentists using the diagnostic methods under study.
      The results from the diagnostic methods were compared with the results from the
      validation method for each observer. The sensitivities for identification of
      cavitated lesions using visual examination ranged from 0.12 to 0.50. For FOTI and
      radiography, the sensitivities ranged from 0.00 to 0.08 and from 0.56 to 0.69,
      respectively. The specificities exceeded 0.90 for all observers with all methods.
      Kappa values expressing inter-observer reproducibility were lowest for FOTI,
      followed by visual and radiographic examination. On the basis of these results,
      it was concluded that FOTI was the least reliable of the diagnostic methods
      tested. For the validation method, the inter-observer agreement was only
      'substantial'. This implies that the method cannot be used as a validation for
      other diagnostic methods applied for the identification of cavitated carious
      lesions in contacting approximal surfaces. However, visual inspection after tooth
      separation may serve as a supplementary diagnostic tool to conventional visual
      and radiographic examination for clinical management of aproximal carious
      lesions.

PMID- 9577985
TI  - The effect of intrinsic fluoride in cows' milk on in vitro enamel
      demineralization.
AB  - The fluoride concentration in cows' milk has been reported to vary with the
      fluoride levels in drinking water but it seldom exceeds 0.5 microg/ml. This
      raised a question as to whether any caries-protective effect could be attributed
      to the intrinsic fluoride of milk. Two samples of cows' milk with intrinsic
      fluoride concentrations of 0.03 and 0.3 microg/ml, respectively, were assessed
      for their protective effect on enamel in an in vitro demineralization model at
      relatively severe and mild acidic challenges (pH 4.6 and 5.0, respectively).
      Polished enamel discs were incubated individually in 5.0 ml of demineralization
      solution for 20 h per day alternated with 1-hour incubations in 1.0 ml of milk or
      control buffers: group 1, demineralization solution only (negative control);
      group 2, milk with 0.03 microg/ml fluoride; group 3, milk with 0.03 microg/ml
      fluoride; supplemented with NaF to 0.3 microg/ml fluoride; group 4, milk with 0.3
      microg/ml fluoride; group 5, 0.3 microg/ml fluoride in 20 mM HEPES, pH 6.7; group
      6, milk with 0.03 microg/ml fluoride supplemented with NaF to 5.0 microg/ml
      fluoride (positive control). The solutions were renewed each day and the calcium
      concentration in the demineralization solutions was followed during 4 days. The
      results showed that the protective effect of intrinsic milk fluoride on enamel is
      limited by the severity of the acidic challenge: There was a significant
      inhibition of the demineralization in groups 3-6 compared to groups 1 and 2, but
      only at pH 5.0 (p<0.0001) and not at pH 4.6 (p = 0.2). The organic components of
      milk had limited protection against demineralization because milk and HEPES with
      the same fluoride concentration gave similar results. The 36% reduction in
      calcium loss at pH 5.0 by treatment with milk with only 0.3 microg/ml fluoride is
      an indication that intrinsic milk fluoride has some caries-protective properties.

PMID- 9577987
TI  - An in vitro comparison between laser fluorescence and visual examination for
      detection of demineralization in occlusal pits and fissures.
AB  - It has been demonstrated that when excited by laser light carious enamel appears
      dark compared to luminescent sound enamel. The aim of this study was to compare
      the sensitivity and specificity of visual exams (V), laser fluorescence (LF) and
      dye-enhanced LF (DELF) for detecting demineralization in occlusal pits and
      fissures. The actual presence of lesions was determined by subsequent confocal
      laser microscopy (CM), which was compared to histology (H). Independent clinical
      examiners visually graded three sites on occlusal surfaces of extracted, human
      premolars as sound or carious and also rated the color of each graded site as: 0
      = same as surrounding enamel; 1 = white; 2 = light brown, or 3 = brown/dark
      brown. An argon laser was used to illuminate the teeth for LF and DELF; the
      images were captured with a CCD camera and then analyzed. DELF images were
      captured after the teeth had been exposed to 0.075% sodium fluorescein. Sections
      were then cut from each specimen and analyzed by CM and H for the presence or
      absence of caries. Results showed that DELF (0.72) was significantly more
      sensitive (p<0.05) than LF (0.49) and V (0.03) for detecting caries, but there
      were no significant differences among the methods in specificity (V 1.00; LF
      0.67; DELF 0.60). When color was used as an indication of caries in V (VC,
      sensitivity 0.47; specificity 0.70), V exams were not different from LF. The area
      under the ROC curve, using H as the gold standard and CM as the test, was 0.78.
      Results indicated that DELF was the best diagnostic tool and that VC and LF were
      equally effective as diagnostic methods, when color of fissures was included as
      an indication of demineralization in the visual exam.

PMID- 9577988
TI  - Autofluorescence and mineral content of carious dentine: scanning optical and
      backscattered electron microscopic studies.
AB  - The aim of this study was to investigate the extent of natural intrinsic
      fluorescence in carious human dentine and any correspondence of such
      autofluorescence (AF) to the mineral distribution within the lesion. Two
      investigative techniques were used, both employing the same sample set and fields
      in diamond-polished block surfaces of polymethylmethacrylate-embedded carious
      teeth. AF at emission wavelengths >515 nm, excited by 488-nm laser light, was
      assessed using a confocal laser scanning optical microscope (CLSM), the
      recordings made under standard operating conditions. The relative mineral content
      was assessed using digital backscattered scanning electron microscopy (20 kV BSE
      SEM). The AF intensity correlated with the level of demineralisation as seen by
      BSE, but the depth of the lesion as seen by CLSM was significantly greater
      implying that the AF is not directly related to the mineral component.

PMID- 9577989
TI  - Fluoride-induced enhancement of diffusion in streptococcal model plaque biofilms.
AB  - It has been demonstrated that fluoride decreases the calcium-binding affinity of
      Streptococcus mutans and approximately doubles the calcium-binding capacity. To
      investigate the effect of this mechanism on calcium mobility in plaque, 45Ca flux
      was measured from a condensed films of S. mutans into tracer-free solution.
      Bacteria were suspended in pH 7.0 or 5.0 buffer including 0, 5, 10, 15 or 20
      mmol/l Ca2+ carrier, with or without 5 mmol/l F- and with 45Ca and 3H-inulin. The
      appearance of 45Ca and 3H-inulin in carrier-containing but initially tracer-free
      buffer was measured and extracellular fraction (Ve) and bound calcium were
      calculated. As the ratio (R) of bound to free Ca2+ approached zero at high
      [Ca2+], the measured diffusion coefficient (rDe) approached the effective
      diffusion coefficient (De), such that: rDe = De/(1+R). Fluoride increased the
      rate of calcium diffusion by a reduction in the binding affinity. This work
      demonstrates that fluoride significantly increases mobility in plaque; this may
      increase the rate at which calcium is transported between plaque and an
      underlying lesion and so promote remineralization. This mechanism could also
      increase the penetration of bacteriocides and suggests a novel method for biofilm
      treatment.

PMID- 9577991
TI  - Substrates of localization-related epilepsies: biologic implications of
      localizing findings in humans.

PMID- 9577990
TI  - Inhibition of salivary amylase by black and green teas and their effects on the
      intraoral hydrolysis of starch.
AB  - Tea decoctions prepared from a number of black and green teas inhibited amylase
      in human saliva. Black teas gave higher levels of inhibition than green teas, and
      removal of tea tannins with gelatin led to the loss of inhibitory activity from
      all decoctions. Streptococcal amylase was similarly inhibited by tea decoctions.
      Fluoride was without effect on amylase. Since salivary amylase hydrolyzes food
      starch to low molecular weight fermentable carbohydrates, experiments were
      carried out to determine whether tea decoctions would interfere with the release
      of maltose in food particles that became entrapped on the dentition. Subjects
      consumed salted crackers and rinsed subsequently for 30 s with black or green tea
      decoctions, or water. Maltose release was reduced by up to about 70% after
      rinsing with the teas. Black tea decoction was significantly more effective than
      green tea, in agreement with the in vitro data. The observations supported the
      hypothesis that tea consumption can be effective in reducing the cariogenic
      potential of starch-containing foods such as crackers and cakes. Tea may reduce
      the tendency for these foods to serve as slow-release sources of fermentable
      carbohydrate.

PMID- 9577992
TI  - Electrophysiologic analysis of the actions of valproate on pyramidal neurons in
      the rat hippocampal slice.
AB  - PURPOSE: Studies in invertebrates and cultured mammalian neurons suggested that
      valproate (VPA) mediates its main antiepileptic effect by slowing the recovery
      from inactivation of voltage-dependent sodium channels. This predicts an effect
      on the refractory period of the action potential and, consequently, on the
      bursting behavior of neurons. METHODS: We investigated this prediction using
      intracellular and extracellular recording techniques in hippocampal slices
      prepared from adult rats. The refractory period (RFP) and the ratio of the slopes
      (SR) of a pair of action potentials were used as indices of the recovery from
      inactivation of sodium channels. They were measured by injecting a series of
      paired depolarizing current pulses into CA1 pyramidal neurons. RESULTS: No
      significant changes were observed in the RFP or SR measured during a 1-h
      recording period when VPA was bath-applied (1 mM), or when it was present in the
      recording electrode (10-50 mM). Lowering the temperature from 34.5 degrees C to
      26.4 degrees C resulted in an increase of the RFP by 100% and a decrease of the
      SR by 40%. However, VPA did not affect any of the measured action potential
      parameters at this lower temperature. VPA was also without effect on the
      presynaptic fiber volley of axons recorded extracellularly in the stratum
      radiatum. The antidromic population spike was unaffected by VPA (2 mM), whereas
      phenytoin (50 microM) clearly affected this spike in the same slices. The absence
      of effect of VPA on each of the measured parameters could not be attributed to
      poor penetration through the slice because bath-applied VPA reduced the frequency
      of extracellularly recorded spontaneous interictal bursts, induced by bicuculline
      and elevated K+, within 10 min. CONCLUSIONS: These findings suggest that at least
      in the hippocampal slice the drug's principal antiepileptic effect cannot be
      explained by its action on voltage-dependent sodium channels.

PMID- 9577993
TI  - Hyposexuality produced by temporal lobe epilepsy in the cat.
AB  - PURPOSE: The hypothesis tested in this study was that a unilateral irritative
      focal epileptic lesion in the temporal lobe results in hyposexuality. METHODS:
      Focal epilepsy was produced in male cats by unilateral injection of aluminum
      hydroxide into either the basolateral amygdala (temporal lobe group) or anterior
      sigmoid gyrus (motor cortex group). Weekly sex testing trials with estrous
      females were conducted prior to and after aluminum hydroxide injection, and
      mating performance scores were compared with those of normal, unoperated cats
      (normal control group). RESULTS: All animals receiving aluminum hydroxide
      developed electroencephalographic and behavioral manifestations of epilepsy;
      i.e., interictal EEG spiking and partial or generalized seizures. Cats in the
      temporal lobe group exhibited a dramatic and complete suppression of sexual
      behavior at periods from 6 to 26 weeks after aluminum hydroxide injection. The
      duration of the hyposexuality varied between individual animals and returned to
      normal as suddenly as the onset occurred, despite the use of AEDs to prevent or
      control generalized seizure activity. Interictal EEG epileptiform spiking in the
      amygdala preceded the onset of hyposexuality by 1-12 weeks. By contrast, cats in
      the motor cortex and normal control groups showed no sign of sexual dysfunction
      throughout the experimental period, independent of seizure activity and/or
      antiepileptic drug (AED) treatment. CONCLUSIONS: These data support the
      hypothesis that hyposexuality occurs as a result of epileptiform activity in the
      temporal lobe, but not in the motor cortex. The precise mechanisms by which this
      occurs are unknown, but are likely to involve abnormally high-frequency neuronal
      activity in temporal lobe structures known to connect with and/or to regulate
      hypothalamic nuclei that organize male sexual behavior toward receptive females.

PMID- 9577994
TI  - The relationship between sleep and epilepsy in frontal and temporal lobe
      epilepsies: practical and physiopathologic considerations.
AB  - PURPOSE: The influence of sleep on the incidence of seizures and the reciprocal
      effects of epilepsy on sleep were analyzed in 30 patients with intractable
      partial seizures, all candidates for surgery. METHODS: The patients were
      classified into two groups of 15 patients according to the documented site of the
      epileptogenic zone: frontal lobe epilepsy (FLE) and medial temporal lobe epilepsy
      (TLE). Frequency and waking-sleep distribution of seizures were evaluated by
      continuous video-EEG monitoring for 5 days, under defined antiepileptic drug
      (AED), sleep, and sleep deprivation regimens. Sleep organization was analyzed by
      polysomnography prior to the presurgical protocol. RESULTS: Significant
      differences were found between the two groups in sleeping-waking distribution of
      seizures under varied conditions, and in the quality of sleep organization. In
      FLE patients, seizures most often occurred during sleep, although sleep
      organization was normal. In TLE patients, most seizures occurred while patients
      were awake, and sleep organization was characterized by a low efficiency index.
      The difference in seizure distribution between FLE and TLE persisted under all
      conditions investigated, i.e., after AED discontinuation and sleep deprivation.
      CONCLUSIONS: Sleep recording may be useful for diagnosis of FLE, and monitoring
      after sleep deprivation for that of TLE. We speculate that sleep-related seizures
      in FLE may depend on interaction between frontal lobe areas with the thalamus
      cortical synchronization system and the acetylcholine regulatory system of
      waking.

PMID- 9577995
TI  - The relationship between quantitative MRI and neuropsychological functioning in
      temporal lobe epilepsy.
AB  - PURPOSE: Quantitative MRI techniques provide an unparalleled opportunity to
      examine in vivo the relationship between the extent and laterality of hippocampal
      pathology and associated neuropsychological deficits. The purpose of this study
      was to examine the nature of the relationship between quantitative measures of
      hippocampal pathology and neuropsychological measures, using a multivariate
      approach. METHODS: We examined the relationship between two MRI measures of
      hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times
      (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy
      patients. RESULTS: As a group, patients with left hippocampal sclerosis (LHS)
      performed more poorly that those with right hippocampal sclerosis (RHS) on
      immediate and delayed prose recall. In the group as a whole, right hippocampal
      volume was significantly correlated with the delayed recall of a complex figure.
      None of the verbal memory test scores were significantly correlated with the
      right or left HCvol or HCT2 measures. However, stepwise multiple regression
      analyses indicated that up to a third of the variation in specific test scores
      could be explained by the quantitative MRI hippocampal measures in conjunction
      with chronological age, and age at onset of habitual epilepsy. Left hippocampal
      measures explained 24% of the variance in the story-recall tasks, while right
      hippocampal measures explained 18% of the variance in a design-learning task and
      32% of the variance in a figure-recall task. CONCLUSIONS: Our results provide
      some support for the lateralised model of material specific memory deficits, but
      suggest that a number of demographic and epilepsy-related factors may interact
      with the extent and laterality of hippocampal pathology in shaping the nature of
      the associated neuropsychological deficit.

PMID- 9577996
TI  - Patient expectations of temporal lobe surgery.
AB  - PURPOSE: The purpose of this study was to examine expectations of postoperative
      quality of life expressed by patients undergoing anterior temporal lobectomy
      (ATL) for the control of intractable seizures. An important component of this
      study was an exploration of the relationship between preoperative expectations
      and perceived success of the operation. METHODS: Psychosocial functioning of 60
      patients was assessed pre- and postoperatively, using a standardised,
      semistructured clinical interview. Preoperative assessment included a detailed
      examination of the patients' expectations of surgery, while postoperative
      assessment at 6 months examined the patients' perception of surgical success with
      respect to seizure outcome and postoperative psychosocial status. RESULTS: A
      range of expectations were expressed about postoperative outcome. These were
      classified into 11 posthoc categories. Patients who perceived the operation as a
      success tended to endorse 'practical' expectations (i.e., driving, employment,
      activities) preoperatively, rather than expectations of a psychologic or social
      nature (i.e., self-change, relationships). These patients experienced fewer
      postoperative seizures and psychosocial difficulties. In contrast, a perceived
      lack of success was associated with greater emphasis on psychosocial expectations
      preoperatively. These patients experienced a greater number of perceived
      postoperative psychosocial difficulties, and more postoperative seizures.
      CONCLUSIONS: Preoperative expectations of surgery formed an important baseline
      against which to assess postoperative outcome, and should constitute a routine
      part of assessment in studies of psychosocial outcome of ATL.

PMID- 9577997
TI  - Ictal behaviors during nonepileptic seizures differ in patients with temporal
      lobe interictal epileptiform EEG activity and patients without interictal
      epileptiform EEG abnormalities.
AB  - PURPOSE: Ictal behaviors during psychogenic nonepileptic seizures (NES) vary
      considerably among individuals, and can closely resemble common semiologies of
      epileptic seizures (ES). We tested the hypothesis that behaviors during NES in
      patients who have temporal spikes would more closely resemble behaviors during ES
      in patients with temporal lobe epilepsy than would behaviors during NES in
      patients who do not have EEG spikes. METHODS: We identified 20 patients who had
      interictal temporal EEG spikes and EEG-video recorded NES (Study Group), 133
      patients with temporal EEG spikes and recorded ES, without NES (Epileptic Group),
      and 24 patients with recorded NES and no epileptiform EEG abnormalities, without
      ES (Nonepileptic Group). RESULTS: The hypothesis was supported with regard to
      ictal motor behaviors. Motionless staring or complex automatisms occurred mainly
      during NES in the Study Group and during ES in the Epileptic Group. In contrast,
      convulsive movements or flaccid falls were most common during NES in the
      Nonepileptic Group. Duration of unresponsiveness was longer, and there were fewer
      postictal states in NES both in the Study and Nonepileptic Groups.
      Unresponsiveness was briefer and postictal states were more consistent in ES in
      the Epileptic Group, however. CONCLUSIONS: Stereotyped motor activities during
      NES presumably represent learned behaviors. Processes underlying acquisition of
      ictal behaviors of NES probably differ in patients with interictal epileptiform
      EEG abnormalities compared to those without. Prior experiences and temporal lobe
      dysfunctions that are associated with epilepsy, and psychological characteristics
      that are unrelated to interictal epileptic dysfunctions, may determine ictal
      behaviors during NES.

PMID- 9577998
TI  - Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic
      interaction?
AB  - PURPOSE: To determine whether the toxicity that occurs in some patients when
      lamotrigine (LTG) is added to carbamazepine (CBZ) is the result of either a
      pharmacokinetic or a pharmacodynamic interaction. METHODS: Escalating LTG doses
      were added to ongoing CBZ treatment in 47 patients. All patients had blood
      samples collected for drug concentration measurement, including the epoxide
      metabolite of CBZ, before starting LTG treatment and after stabilising at each
      dose escalation. Patients also were examined for signs of toxicity. RESULTS:
      After LTG was introduced, nine patients demonstrated clinical signs of CNS
      toxicity, mainly diplopia and dizziness. There was no significant (p = 0.05)
      change in the serum concentrations of either CBZ or its epoxide metabolite when
      LTG was added either to the group as a whole or to the nine patients who
      experienced adverse CNS effects. LTG serum concentrations also were below the
      level at which the common signs of LTG toxicity, such as nausea, vomiting, or
      unsteadiness, are more likely to occur. In seven of the nine patients who
      exhibited CNS toxicity, CBZ serum concentrations were >8 mg/L on LTG
      introduction. CONCLUSIONS: Toxicity is more likely to occur when LTG is added to
      CBZ if the initial CBZ level is high, typically >8 mg/L. This appears to be the
      result of a pharmacodynamic interaction. A reduction of CBZ dose usually resolves
      the toxicity, allowing the LTG dose to be escalated to maximal effect. It is not
      usually necessary to stop either drug.

PMID- 9577999
TI  - Conversion to high dose gabapentin monotherapy in patients with medically
      refractory partial epilepsy.
AB  - PURPOSE: To evaluate the safety and efficacy of high dose gabapentin (GBP)
      monotherapy (3,000-4,800 mg/day) in patients with medically refractory partial
      epilepsy. METHODS: GBP monotherapy at daily doses up to 4,800 mg was attempted in
      patients participating in the open-label phase of a double-blind, dose
      controlled, GBP monotherapy trial. For those who achieved monotherapy, the types
      and severity of adverse events were assessed and the average seizure frequency
      per 28 days while maintained on the highest daily GBP dose was compared to the
      seizure frequency during the baseline phase of the double blind trial.
      Correlation analysis between GBP serum level, total daily dose, and percentage of
      seizure change from baseline was performed. RESULTS: A total of 45 patients
      participated in the open-label phase of the trial and 23 (51%) were converted
      successfully to GBP monotherapy. In those patients, the average daily gabapentin
      dose was 3,900 mg and the mean length of follow-up was 252 days. Compared to
      baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial,
      complex partial and secondarily generalized seizures respectively, while
      maintained on high-dose GBP monotherapy. A significant linear correlation between
      daily GBP dosage (2,400-4,800 mg) and resultant mean serum levels was found (r =
      0.51; p < 0.01). There was no significant correlation between seizure frequency
      and total daily GBP dose or with serum levels. High-dose GBP monotherapy was well
      tolerated; only one patient exited the trial because of adverse events. The most
      common adverse event was tiredness/sleepiness and was not dose-related.
      CONCLUSIONS: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg
      and is effective in a subgroup of patients with medically refractory partial
      epilepsy.

PMID- 9578000
TI  - Rapid switchover to carbamazepine using pharmacokinetic parameters.
AB  - PURPOSE: The standard practice of switching patients to carbamazepine (CBZ)
      involves initiating a low dose and raising it by small increments until the
      desired dose is reached, to avoid intolerable adverse effects (AE). In a pilot
      study, a protocol using single-dose kinetic studies was developed to switch
      patients to CBZ through rapid-dose increments and to manage concurrent rapid
      taper of the previous antiepileptic drugs (AEDs) without causing AE. The purpose
      of this prospective study was (a) to reassess whether a rapid switchover to CBZ
      could be done with minimal or no AE and without causing an increase in seizures;
      (b) to determine whether the maintenance dose of CBZ predicted at the time of the
      single-dose kinetic study can yield the desired concentration at steady state
      (Css); and (c) to determine the degree to which the calculated maintenance dose
      of CBZ will need to be adjusted after the previous AED has been discontinued for
      a four-week period. METHODS: Twenty-five patients taking phenytoin (PHT) and/ or
      phenobarbital (PB) and/or primidone (PRM) underwent a rapid switchover to CBZ
      following a 10 mg/kg single-dose kinetic study (day 1) which allowed calculation
      of a maintenance dose necessary to yield a mean Css of 10.2 (+/-2.2) mg/l. On day
      2, patients received a CBZ dose equivalent to 10 mg/kg + 200 mg; thereafter, they
      underwent daily dose increments of 200 mg until the calculated maintenance dose
      was reached. Dose increments were modified in the case of AE. Concurrent tapering
      of the previous AED was started as of day 1: PHT by 100 mg/day, while PB and PRM
      were stopped on day 1; PB was restarted before patients were to be discharged
      from the hospital if a PB serum concentration above 10 mg/l was identified at
      that time. Pharmacokinetic data and occurrence of AE were compared between the
      two groups at the time of the single-dose kinetic study, at the completion of the
      switchover to CBZ, and 4 weeks after discontinuation of the previous AED.
      RESULTS: All patients completed the switchover to CBZ within a mean time period
      of 6 days (+/-2), reaching a mean maintenance dose of 1,639 mg/day (+/-370) which
      yielded a mean Css of 11.3 (+/-3.2) mg/l. The maintenance dose had to be lowered
      by 20.4% (+/-8.3) in 59% of patients within the four-week period following
      discontinuation of at least one of the previous AEDs. None of the patients
      experienced an increase in seizure frequency relative to baseline. Fifteen (60%)
      patients had no AE; five (20%) experienced AE of mild severity. AE rated as
      moderately severe (n = 4) or severe (n = 1) occurred in patients with a static
      encephalopathy (p = 0.02, Fisher's exact test) and among patients > or =55 years
      (p = 0.017, Fisher's exact test). CONCLUSIONS: A rapid switch-over to CBZ from
      PHT, PB, or PRM can be carried out safely with no, or minimal, AE in young
      adults, unless they suffer from static encephalopathy.

PMID- 9578001
TI  - Vagus nerve stimulation for symptomatic generalized epilepsy: a pilot study.
AB  - PURPOSE: Patients with symptomatic generalized epilepsy (SGE) may have
      antiepileptic drug (AED)-resistant mixed generalized seizures. Vagus nerve
      stimulation (VNS) reduces partial seizures and may help SGE. METHODS: We added
      VNS to stable AED therapy in five SGE patients. Nine-month postoperative VNS
      treatment seizure rates were compared to a 1-month preoperative baseline.
      RESULTS: All patients had mixed generalized seizures, EEG generalized slow spike
      and-wave and behavioral abnormalities. Median number of previous AEDs taken was 6
      (range 5-12). Median baseline seizure rate was 75/month (range 29-110). VNS
      produced a median seizure rate production of -41% (range -40% - -85%). Adverse
      events reported in one patient each were: incisional infection, choking sensation
      and voice change; and coughing (noted by two patients). One patient discontinued
      VNS due to coughing. CONCLUSIONS: We conclude that VNS may be useful add-on
      therapy for SGE. A larger, controlled, and blinded trial may be warranted.

PMID- 9578002
TI  - Epilepsy, vagal nerve stimulation by the NCP system, mortality, and sudden,
      unexpected, unexplained death.
AB  - PURPOSE: To determine rates of all-cause mortality and of sudden, unexpected,
      unexplained deaths in epilepsy (SUDEP) in a cohort of individuals treated with
      the Neuro Cybernetic Prosthesis (NCP) System for intractable epilepsy, and; to
      contrast the NCP experience with other epilepsy cohorts. METHODS: A cohort of 791
      individuals were followed for 1,335 person-years from implantation. Of the total
      cohort, 120 individuals had their NCP System devices deactivated. The 15 deaths
      which occurred during NCP System activation were reviewed for SUDEP by a panel.
      There were three additional deaths and 242.5 person-years of monitoring after
      deactivation. RESULTS: The standardized mortality ratios for NCP System were 5.3,
      95% confidence interval (CI) 3.0-8.7; and for the time period after device
      deactivation, 4.4, 95% CI 0.9-12.8. Six of the deaths during stimulation were
      considered definite or probable SUDEP and two as possible SUDEP. Seven were not
      considered to be SUDEP. The incidence of definite/probable SUDEP was 4.5 per
      1,000 person-years and 6.0 per 1,000 person-years for definite/probable/possible
      SUDEP. CONCLUSIONS: The mortality rates and standardized mortality ratios are
      comparable with studies of young adults with intractable epilepsy who were not
      treated with NCP System. These SUDEP rates are not significantly different from
      those reported in the recent studies of lamotrigine (LTG), gabapentin (GBP), and
      tiagabine (TGB). The higher rates of SUDEP in the NCP System cohort, as compared
      with recent drug trials, presumably is explained by the selection of relatively
      higher-risk patients for the NCP System device.

PMID- 9578003
TI  - Commission on Outcome Measurement in Epilepsy, 1994-1997: final report.

PMID- 9578004
TI  - The utility of the lh/lh mutant mouse as a animal model of human absence
      epilepsy.

PMID- 9578005
TI  - Review of new antiepileptic drugs (AEDs)

PMID- 9578006
TI  - Do antiepileptic drugs exacerbate seizures?

PMID- 9578007
TI  - Antiepileptic drugs as a cause of worsening seizures.
AB  - PURPOSE: Although the paradoxical ability of antiepileptic drugs (AEDs) to
      increase seizure activity has been recognized for decades, the underlying
      mechanisms are poorly understood and few systematic studies have addressed this
      problem. This article is intended to provide a critical review of available
      literature on this topic. METHODS: Information was collected by means of
      computerized literature searches, screening of journals and textbooks, and
      consultation with colleagues. Mechanisms which potentially might precipitate
      underlying drug-induced exacerbation of seizures were considered based on
      available pharmacologic and clinical knowledge. RESULTS: The reviewed information
      suggests that a paradoxical increase in seizure frequency may occur as a result
      of at least two separate mechanisms. The first appears to involve a nonspecific
      manifestation of drug intoxication; seizure-worsening in this context is usually
      reversible by dosage reduction or elimination of unnecessary polypharmacy.
      Conversely, the other mechanism may involve a distinct adverse primary action of
      the drug in specific seizure types or in syndromic forms. Carabamazepine, in
      particular, has been reported to precipitate or exacerbate a variety of seizures,
      most notably absence, atonic, or myoclonic seizures in patients with generalized
      epilepsies characterized by bursts of diffuse and bilaterally synchronous spike
      and-wave EEG activity. Phenytoin and vigabatrin also have been implicated in
      worsening of seizures, particularly generalized seizures, whereas gabapentin has
      been associated repeatedly with precipitation of myoclonic jerks. Benzodiazepines
      occasionally have been reported to precipitate tonic seizures, especially when
      given intravenously to control other seizure types in patients with Lennox
      Gastaut syndrome. Seizure deterioration has been reported also with other drugs;
      though in most cases evidence is still insufficient for meaningful conclusions to
      be drawn. CONCLUSIONS: Drug-induced exacerbation of seizures is a serious and
      common clinical problem that is often unrecognized or overlooked by the treating
      physician. Its occurrence appears to be related to three possible causes: an
      incorrect diagnosis of seizure type or syndromic form, lack of knowledge about
      certain drugs that are contraindicated in specific types of epilepsies, or to
      prescription of excessive drug dosages and drug combinations. Further studies are
      required to evaluate the prevalence of this phenomenon of drug-induced
      exacerbation of seizures, to investigate its mechanisms in greater detail and to
      characterize additional prognostic factors that may be used for early
      identification of patients at risk.

PMID- 9578008
TI  - Treatment of refractory status epilepticus with propofol: clinical and
      pharmacokinetic findings.
AB  - PURPOSE: We compared propofol with high-dose barbiturates in the treatment of
      refractory status epilepticus (RSE) and propose a protocol for the administration
      of propofol in RSE in adults, correlating propofol's effect with plasma levels.
      METHODS: Sixteen patients with RSE were included; 8 were treated primarily with
      high-dose barbiturates and 8 were treated primarily with propofol. RESULTS: Both
      groups of patients had multiple medical problems and a subsequent high mortality.
      A smaller but not statistically significant fraction of patients had their
      seizures controlled with propofol (63%) than with high-dose barbiturate therapy
      (82%). The time from initiation of high-dose barbiturate therapy to attainment of
      control of RSE was longer (123 min) than the time to attainment of seizure
      control in the group receiving propofol (2.6 min, p = 0.002). Plasma
      concentrations of propofol associated with control of SE were 14 microM +/- 4
      (2.5 microg/ml). Recurrent seizures were common when propofol infusions were
      suddenly discontinued but not when the infusions were gradually tapered.
      CONCLUSIONS: If used appropriately, propofol infusions can effectively and
      quickly terminate many but not all episodes of RSE. Propofol is a promising agent
      for use in treating RSE, but more studies are required to determine its true
      value in comparison with other agents.

PMID- 9578009
TI  - Reversible pseudoatrophy of the brain and mental deterioration associated with
      valproate treatment.
AB  - PURPOSE: To describe an 11-year-old girl with symptomatic localization-related
      epilepsy and normal intelligence who developed reversible mental deterioration
      and pseudoatrophic brain changes while receiving valproate (VPA). METHODS:
      Assessment of mental function using Wechsler Intelligence Scale for Children-III
      (WISC) and Raven's Progressive Matrices (PM), EEG recordings while awake and
      asleep, and brain magnetic resonance imaging (MRI), were performed at the
      beginning of VPA therapy, after 2 years and 8 months of treatment and following
      VPA discontinuation. RESULTS: After 2 years and 6 months on VPA (< or = 26
      mg/kg/day) the girl insidiously developed mental deterioration (loss of 18 IQ
      points and drop in age-adjusted PM score from the 95th to the 50th percentile)
      associated with MRI-documented pseudoatrophy of the brain. Onset of severe
      cognitive impairment coincided with serum VPA concentrations near 100 microg/ml.
      There were no other manifestations of drug toxicity or hyperammonemia. Background
      EEG activity was normal. Reduction of VPA dosage and subsequent discontinuation 4
      months later resulted in disappearance of clinical symptoms with a 20-point
      improvement at IQ testing and recovery of previous PM score. Repeat MRI showed
      disappearance of pseudoatrophic changes. CONCLUSIONS: The striking cognitive
      improvement and reversal of pseudoatrophic brain changes following VPA
      discontinuation strongly suggest a drug-induced condition. Based on this and
      previous reports, the syndrome of VPA-associated mental deterioration and
      pseudoatrophy of the brain appears to encompass different but possibly related
      clinical entities, which include parkinsonism with cognitive deterioration,
      mental deterioration with signs of VPA-toxicity, and isolated mental
      deterioration, as seen in our patient. A drug-induced effect should be considered
      whenever cognitive deterioration and imaging findings of brain atrophy occur in
      VPA-treated patients.

PMID- 9578010
TI  - Effects of tiagabine monotherapy on abilities, adjustment, and mood.
AB  - PURPOSE: We evaluated the dose-related impacts of tiagabine (TGB) on cognition
      and mood in a monotherapy study. METHODS: Patients were 123 adults with
      uncontrolled partial seizures, each treated with a single currently available
      antiepileptic drug (AED) for management of clinical epilepsy. They completed a
      battery of neuropsychological tests during an 8-week prospective baseline period
      and once again at the end of the 12-week fixed-dose period (or earlier if they
      dropped out of the study). Sixty-six patients were randomized to 6 mg/day TGB and
      57 were randomized to 36 mg/day TGB. RESULTS: Few changes in either abilities or
      adjustment and mood were noted when all patients were considered as a single
      group. However, analysis of both dose and attainment of TGB monotherapy showed
      that patients receiving TGB monotherapy did best, improving particularly in the
      areas of adjustment and mood with low-dose TGB and in the area of abilities with
      high-dose TGB. Patients who did not attain monotherapy showed no change except
      that the high-dose group did not perform as well on measures of mood and
      adjustment. Baseline AED and changes in seizure control did not affect the
      results. CONCLUSIONS: Patients' attainment of TGB monotherapy was associated with
      their achievement of positive changes of varying degree on psychological tests.
      Failure to attain TGB monotherapy was associated with no changes on the tests
      except in patients receiving high-dose TGB where it appeared that some
      alterations in mood might have been avoided if a slower titration schedule had
      been used.

PMID- 9578011
TI  - Effect of renal impairment on the pharmacokinetics and tolerability of tiagabine.
AB  - PURPOSE: We wished to determine the effect of renal impairment on the
      pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
      METHODS: We assessed TGB pharmacokinetics and tolerability in 25 subjects with
      various degrees of renal function (based on creatinine clearance, n = 4-6 per
      group) from healthy (group I) to requiring hemodialysis (group V) in a single and
      multiple dose (every 12 h), one-period (groups I-IV) or a single dose, two-period
      (group V) study (4-mg oral doses of TGB x HCl). Blood samples were collected
      after the first dose (both periods for group V) and after the last dose on day 5
      (groups I-IV). TGB plasma concentrations and plasma protein binding were
      determined by high-performance liquid chromatography (HPLC) and ultrafiltration,
      respectively. RESULTS: TGB was well tolerated by all study subjects. The
      pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic
      parameter (based on either total or unbound concentrations) was statistically
      correlated with creatinine clearance. For total TGB in plasma, single-dose mean
      values of the maximum plasma concentration, clearance, and half-life (t(1/2))
      ranged from 52 to 108 ng/ml, from 7.14 to 11.02 l/h, and from 6.4 to 8.4 h,
      respectively. CONCLUSIONS: TGB pharmacokinetics and tolerability were independent
      of renal function; therefore, dosage adjustment is unnecessary for epilepsy
      patients with renal impairment.

PMID- 9578012
TI  - The syndromic classification of the International League Against Epilepsy: a
      hospital-based study from South India.
AB  - PURPOSE: To determine the distribution of various epilepsies and epileptic
      syndromes in the epileptic population treated in a university hospital in a
      developing country. METHODS: Data concerning 2,531 patients with epilepsy seen
      between January 1989 and June 1994 were analyzed using the International League
      Against Epilepsy (ILAE) classification. RESULTS: Of 2,531 cases, 48% fell into
      ILAE categories 1.3, 3.2, or 4.1 (cryptogenic, without unequivocal generalized or
      focal seizures; or situation-related seizures, respectively). Localization
      related epilepsies (LREs) and epileptic syndromes (1.1, 1.2, 1.3) were found in
      1,591 (62.9%) patients; of these patients, symptomatic localization-related
      epilepsies totaled 62.7%. and idiopathic localization-related epilepsies
      accounted for only 0.7%. Juvenile myoclonic epilepsy was the most common type of
      idiopathic generalized epilepsy (IGE), comprising 4.9% of the total study
      population and 7.7% of patients registered in the epilepsy clinic. A combination
      of childhood and juvenile absence epilepsies were found in only 0.4% of the total
      study population. Single computed tomography (CT) enhancing lesion (SCTEL) and
      focal cerebral calcification (FCC) accounted for 22% of the etiologic factors for
      localization-related epilepsies. Neurologic deficits were found in 9.5% of
      patients with SCTEL; none were found with FCC. None of the patients with these
      lesions had any history of antecedent events that suggested CNS involvement. In
      patients with localization-related epilepsies with unremarkable clinical data,
      the proportion of CT scans showing SCTELs was 39 (95% confidence interval [CI],
      0.35-0.43) and 0.18 (95% CI, 15-0.21) for FCCs. The proportion for both lesions
      together was 0.57 (95% CI, 0.53-0.61). Seizures did not recur once the lesion
      resolved in patients with SCTELs. In patients with FCCs, seizure remission was
      71.5% (95% CI, 53.7-85.4) at 3 years. CONCLUSIONS: This study illustrates the
      rarity in one patient population of some of the syndromes and categories
      described in the ILAE classification. Childhood and juvenile absence epilepsies
      together formed a small proportion. SCTEL and FCC were important etiologic
      factors for localization related epilepsies. The epilepsy associated with SCTEL
      was a form of benign epilepsy; epilepsy associated with FCC had remission rates
      similar to other remote symptomatic epilepsies. Without neuroimaging evidence,
      these 2 lesions would have been missed and the patients might have been grouped
      under cryptogenic localization related epilepsy. For this reason, we emphasize
      the need for neuroimaging in patients with localization related epilepsies with
      unremarkable clinical findings, before classification into the cryptogenic
      category. In the absence of neuroimaging, such patients should be classified as
      "probably cryptogenic."

PMID- 9578013
TI  - Evidence of late-onset infantile spasms.
AB  - PURPOSE: To underline the unusual but possible occurrence of epileptic spasms
      (ES) in children >1 year of age. METHODS: Cases in whom onset of spasms occurred
      after 1 year of age were identified through a retrospective review of the records
      of all patients referred for ES to the Saint-Vincent de Paul Hopital (Paris) and
      American Memorial Hospital (Reims) between 1974 and 1994. RESULTS: Eighteen cases
      were identified among the 734 children referred for ES, 18 cases were identified
      where spasm onset time ranged from 12 to 38 months of age. In 1/3 of the cases,
      the diagnosis was suspected from the onset of clinical manifestations; in the
      remaining 2/3, diagnosis was delayed by a mean 6 months (range, 2-25 months).
      Neurobehavioral regression affected two-thirds of the patients. Modified
      hypsarrhythmia was present in 11 patients; all but one exhibited major and
      diffuse spike- and slow-wave activity. EEG abnormalities were detected in the
      frontal areas in 11 patients. Spasms were cryptogenic in 9 patients. Steroids
      were administered to 13 patients; these controlled the spasms in 6 patients.
      Outcome was favorable for both seizures; cognition favorable in only 2 of the 18
      patients. CONCLUSIONS: Beginning after the first year of life, ES, or late-onset
      infantile spasms, are distinct from early Lennox-Gastaut syndrome, although
      etiology, prognosis and treatment are similar to that for the classical infantile
      spasms.

PMID- 9578014
TI  - Predicting outcome of anterior temporal lobectomy using simulated neural
      networks.
AB  - PURPOSE: Anterior temporal lobectomy (ATL) is an important option for treatment
      of medically refractory seizures. Patient selection is not always clear-cut, and
      there is inherent morbidity and mortality associated with the invasive and
      expensive surgical protocols. To determine whether patient selection might be
      facilitated by application of artificial intelligence, we developed a model that
      predicted seizure outcome after ATL, using a simulated neural network (SNN).
      METHODS: Predictions of the model were compared with predictions derived from
      conventional discriminant function analysis. Neural networks and discriminant
      functions were devised that would predict the occurrence of both Class 1 outcomes
      (totally seizure-free), and Class 1 or Class 2 outcomes (nearly or totally
      seizure-free), using data from 87 patients from three surgical centers. The SNNs
      and discriminant functions were developed using data from a randomly selected
      subsample of 65 patients, and both models were cross-validated, using the
      remaining 22 patients. RESULTS: The discriminant functions showed overall
      predictive accuracy of 78.5% and 72.7%, while the neural networks demonstrated
      overall accuracy of 81.8% and 95.4%. CONCLUSIONS: Simulated neural networks show
      promise as adjuncts to decision-making in the selection of epilepsy surgery
      patients.

PMID- 9578015
TI  - Correlation between interictal regional cerebral blood flow and depth-recorded
      interictal spiking in temporal lobe epilepsy.
AB  - PURPOSE: Single photon emission computed tomography (SPECT) is used as an
      adjunctive method in preoperative localization of epileptic foci. In temporal
      lobe epilepsy (TLE), interictal hypoperfusion is observed in 60-70% of cases.
      Correlation with ictal EEG changes is observed in approximately 50-60% of cases.
      Relationships with interictal EEG have been studied less. We compared interictal
      SPECT data obtained in 20 patients with their interictal intracerebral electrical
      activity recorded by depth electrodes to evaluate a potential relationship.
      METHODS: We studied 20 sequential patients whose clinical, surface, and depth EEG
      data indicated seizure originating in the temporal lobe and who had interictal
      [99mTc]hexamethylpropylene amine oxime (HMPAO)-SPECT stereo-EEG (SEEG).
      Intracerebral electrodes were placed according to the patient's profile. The
      interictal extent of epileptiform activity allowed delineation of the irritative
      zone. Interictal spike frequency was also analyzed semiquantitatively. Visual and
      numerical SPECT analysis was performed blind to SEEG data. RESULTS: Interictal
      hypoperfusion was observed in 16 patients, involving the epileptogenic temporal
      lobe in 14. Except for 1 patient who manifested lateral temporal hypoperfusion
      corresponding to a mass lesion, two distinctive patterns of hypoperfusion were
      noted: (a) mesial hypoperfusion (5 patients), and (b) global temporal
      hypoperfusion (8 patients). In 8 patients, hypoperfusion had also extended into
      the adjacent cortex. Temporal mesial hypoperfusion was associated with spiking
      limited to the mesial structures, whereas global temporal hypoperfusion or
      hypoperfusion extending beyond the temporal lobe was associated with a similar
      topographic pattern of spikes. CONCLUSIONS: Comparison between SPECT and SEEG
      data collected in the interictal phase indicated that the extent of the
      hypoperfused area correlated topographically with that of the underlying
      irritative zone.

PMID- 9578016
TI  - Seizures with fever after unprovoked seizures: an analysis in children followed
      from the time of a first febrile seizure.
AB  - PURPOSE: To determine how the onset of unprovoked seizures influences recurrence
      of seizures with fever in children followed from the time of a first febrile
      seizure. METHODS: In a prospective cohort of children (n = 428) identified at the
      time of a first febrile seizure, predictors of a second seizure with fever were
      identified. The occurrence of a first unprovoked seizure was treated as a time
      dependent covariate in a Cox regression model rather than as a censoring point as
      it traditionally has been in the past. RESULTS: One hundred forty-three (33.4%)
      children had further seizures. Seven had further seizures with fever only after
      onset of unprovoked seizures. After adjustment was made for the four previously
      described predictors of recurrent febrile seizures (age at onset, family history,
      height of fever, and duration of fever), the onset of unprovoked seizures was
      associated with a rate ratio of 3.47 (p = 0.0015), indicating a large increase in
      the risk of further seizures with fever after onset of unprovoked seizures.
      CONCLUSIONS: Young children who develop unprovoked seizures after a febrile
      seizure are at substantial risk for further seizures with fever. This may
      represent part of the spectrum of benign febrile seizures or it may represent the
      so-called "epilepsy triggered by fever" spectrum. It affects only a small
      proportion of children with febrile seizures; however, in some children, it may
      be useful information to consider when making treatment decisions.

PMID- 9578017
TI  - Development and cross-cultural translations of a 31-item quality of life in
      epilepsy inventory.
AB  - PURPOSE: We report the development of a questionnaire to assess health-related
      quality-of-life (HRQOL) in people with epilepsy and the process of cross-cultural
      translations of the questionnaire. METHODS: A sample of 304 adults with epilepsy
      from 25 seizure clinics in the United States was used to derive an abbreviated
      questionnaire focusing on epilepsy-related issues from a longer, 89-item
      instrument (QOLIE-89). A rigorous forward-backward-forward system was used for
      cross-cultural translation. RESULTS: A 31-item questionnaire (QOLIE-31, version
      1.0) resulted, comprising seven subscales covering general and epilepsy-specific
      domains. Subscale and total scores can be calculated. The subscales were grouped
      into two factors: Emotional/Psychological Effects (seizure worry, overall QOL,
      emotional well-being, energy/fatigue subscales) and Medical/Social Effects
      (medication effects, work-driving-social limits, cognitive function subscales).
      Cross-cultural translations were made from U.S.-English into Danish, Dutch,
      German, Canadian French, French, Italian, Spanish, Swedish, and U.K. English
      Versions 1.1. CONCLUSIONS: Our results support the reliability and validity of
      the QOLIE-31 (U.S.-English version 1.0) as a measure of HRQOLIE. Cross-cultural
      translations into nine other languages make it feasible to use the QOLIE-31
      (version 1.1) in multinational clinical trials after validation in each
      population or concurrent with the clinical trial.

PMID- 9578018
TI  - Long-term survival of people with unprovoked seizures: a population-based study.
AB  - PURPOSE: Few population-based studies of long-term survival in people with
      seizures or epilepsy have been made. METHODS: Between January 1, 1960 and
      December 31, 1964, we identified 224 incidence cases of unprovoked seizures in
      Iceland and determined survivorship status and date of death for the cases as of
      January 1, 1996. We compared survivorship with that expected based on data from
      age-/sex-specific life tables from the country for 1961-1990 and calculated the
      standardized mortality ratio (SMR). RESULTS: By 30 years after diagnosis, there
      were 45 deaths among patients with unprovoked seizures as compared with an
      expected 28 deaths [standardized mortality ratio (SMR) 1.6; 95% confidence
      interval (CI) 1.2-2.2]. Patients with unprovoked seizures of unknown etiology did
      not have a significant increase in mortality overall (SMR 1.3, 95% CI 0.8-1.9) or
      in any time interval. For patients with remote symptomatic unprovoked seizures,
      mortality was increased (SMR 2.3, 95% CI 1.4-3.5). This increase was attributable
      to excess mortality for the first 15 years after diagnosis (SMR 4.1, 95% CI 2.4
      6.6), and SMR was not different after that time. CONCLUSIONS: Survivorship was
      decreased for the population of patients with unprovoked seizures. The increased
      mortality was primarily due to excess mortality in patients with remote
      symptomatic seizures, occurring in the first 15 years after diagnosis. Overall
      mortality for idiopathic unprovoked seizures was not significantly increased.

PMID- 9578019
TI  - Startle epilepsy with infantile hemiplegia: report of two cases improved by
      surgery.
AB  - PURPOSE: To study the effectiveness of surgical therapy on 2 patients with
      startle epilepsy with infantile brain damage (SEIBD), a rare but distinctive
      epileptic syndrome characterized by motor seizures resistant to antiepileptic
      drugs (AEDs). METHODS: The patients with SEIBD both had hemiplegia, due to gross
      contralateral hemispheric lesions, and suffered from tonic postural seizures,
      frequently provoked by sudden unexpected somatosensory stimuli on the paretic
      side of the body. These attacks occasionally caused the patients to drop to the
      floor, and mild-to-moderate injuries had been sustained; they were resistant to
      all currently available AEDs. Consequently, these daily drop attacks severely
      restricted the patients' social lives and school participation. Both patients
      underwent corpus callosotomy and resection of epileptogenic premotor and
      supplementary motor lesions. One patient also underwent additional multiple
      subpial transections of the primary sensorimotor area. RESULTS: Seizures, as well
      as quality of life, improved dramatically in both patients after surgery.
      CONCLUSIONS: Startle epilepsy with infantile hemiplegia is a distinct epileptic
      syndrome characterized by structural brain damage restricted primarily to one
      hemisphere, large ipsilateral epileptogenic lesions involving the
      perisensorimotor area, refractory startle-provoked drop attacks, and a good
      response to epilepsy surgery.

PMID- 9578020
TI  - NER rat strain: a new type of genetic model in epilepsy research.
AB  - PURPOSE: We characterized and evaluated as an animal model of epilepsy NER, a new
      epileptic rat strain, which was developed by inbreeding rats with spontaneous
      tonic-clonic seizures in a stock of Crj:Wistar. METHODS: Animals were monitored
      through the inbreeding course, and video-EEGs were recorded selectively. External
      seizure-provoking stimuli were applied to NER and to a control parental strain.
      F1, F2, and backcross progenies were produced between NER and a nonepileptic
      unrelated strain. Pathologic study included hematoxylin-and-eosin (HE), Kluver
      Barrera's, modified Bodian silver, and neo-Timm's staining. RESULTS: After the F9
      generation, 94%-98% of NER exhibited spontaneous tonic-clonic convulsions,
      beginning with neck and forelimb clonus, wild jumping/running, opisthotonic
      posturing, and evolving to tonic, then clonic convulsion, followed by postictal
      flaccidity. Most seizure onsets occurred between 2-4 months of age, and the
      incidence was 0.45 +/- 0.21 seizures in 12 h. Ictal cortical and hippocampal EEGs
      were characterized by high-voltage spikes followed by diffuse spike-and-wave or
      polyspike-and-wave complexes. NER revealed seizure susceptibility to
      pentylenetetrazol, tossing, and transcorneal electroshock, but not to tactile,
      photic, or acoustic stimuli, or to transauricular electroshock. Mating
      experiments revealed that 0% (0/46) of the animals in F1, 25.5% (13/51) in F2,
      and 63.6% (56/88) in backcross progenies exhibited spontaneous tonic-clonic
      convulsions without sex difference. For all these epileptic traits, no pathologic
      changes were demonstrated in the CNS. CONCLUSIONS: NER frequently exhibited
      spontaneous convulsions, controlled by a major autosomal recessive gene for
      epilepsy, that are comparable to generalized tonic-clonic seizures in humans.
      This can serve as a new genetic model in epilepsy research.

PMID- 9578021
TI  - Excellent surgical results obtained in patients with a depressed frontal fracture
      leading to frontal encephalomalacia and intractable frontal seizures.

PMID- 9578022
TI  - Contradictory conclusions about the possible effects of prolonged febrile
      convulsions.

PMID- 9578023
TI  - Brain hypometabolism in a model of chronic focal epilepsy in rat neocortex.
AB  - PURPOSE: Metabolic mapping of the human brain has become a widely used method for
      identifying and localizing epileptic foci. A reduction of glucose consumption
      usually is found interictally in the area of the focus. By contrast, animal
      models of acute epilepsy show a hypermetabolism in the epileptic focus. Here we
      investigated how metabolism is altered in an animal model of chronic epilepsy
      caused by focal injection of tetanus toxin into rat neocortex. METHODS: A total
      of 27 male Wistar rats were anesthetized and injected into the motor or sensory
      cortex either with dissolved tetanus toxin or with the solvent only. Animals
      recovered for 7, 14, or 30 days and then were anesthetized again for quantitative
      14C-deoxyglucose autoradiography. Data were analyzed with an imaging program, and
      regional cerebral glucose metabolism (rCMRGlc) was determined. RESULTS: Injection
      of tetanus toxin into the motor cortex caused a focal hypometabolism which was
      confined to the cytoarchitectonic boundaries of the injected area, whereas
      sensory cortex injection caused a more widespread hypometabolism in all sensory
      cortical and connected, areas. None of the animals displayed focal
      hypermetabolism and we observed no significant time-dependent alteration of brain
      metabolism. CONCLUSIONS: Tetanus toxin injection into the cortex of the rat
      induces chronic epileptic activity accompanied by a focal hypometabolism. The
      data suggest that the spread of the metabolic alterations depends on the
      connectivity of the injected cortical area.

PMID- 9578024
TI  - Astrocytes from human hippocampal epileptogenic foci exhibit action potential
      like responses.
AB  - PURPOSE: We studied Na+ channel expression and the ability to generate action
      potential (AP)-like responses in primary cultures of human astrocytes by whole
      cell patch-clamp recording techniques. METHODS: Tissue samples from 22 patients
      with various classifications of temporal lobe epilepsy (TLE) were plated to form
      separate astrocyte cultures from three regions; the hippocampus, parahippocampus,
      and anterolateral temporal neocortex. RESULTS: The resting membrane potential of
      seizure focus astrocytes (MTLE, mesial TLE) was significantly depolarized
      (approximately -55 mV) as compared with cortical astrocytes (-80 mV). Hippocampal
      astrocytes from other substrates for TLE (MaTLE, mass-associated TLE; PTLE,
      paradoxical TLE) in which the hippocampus is not the seizure focus displayed
      resting membrane potentials similar to those of neocortical astrocytes
      (approximately -75 mV). Astrocytes from the seizure focus (MTLE) displayed much
      larger tetrodotoxin (TTX)-sensitive Na+ currents with -66-fold higher Na+ channel
      density (113.5 +/- 17.41 pA/pf) than that of comparison neocortical astrocytes
      (1.7 +/- 3.7 pA/pf) or than that of the hippocampal and parahippocampal
      astrocytes of the MaTLE and PTLE groups. As a consequence of this higher channel
      density, seizure focus astrocytes were capable of generating AP-like responses.
      However, at the resting potential, most Na+ channels are inactive and no
      spontaneous firing was observed. In contrast, astrocytes in the comparison
      neocortex from all groups and the hippocampus and parahippocampus from the MaTLE
      and PTLE groups could not fire AP-like responses even after large current
      injections. CONCLUSIONS: The function of Na+ channels in these astrocytes is
      unclear. However, the marked differences in seizure focus astrocytes as compared
      with cortical and nonseizure focus hippocampal astrocytes suggest a more active
      role for astrocytes associated with hyperexcitable neurons at a seizures focus.

PMID- 9578025
TI  - Effects of phenytoin, carbamazepine, and gabapentin on calcium channels in
      hippocampal granule cells from patients with temporal lobe epilepsy.
AB  - PURPOSE: The anticonvulsants phenytoin (PHT), carbamazepine (CBZ), and gabapentin
      (GBP) are commonly used in the treatment of temporal lobe epilepsy. Ca2+ current
      modulation has been proposed to contribute to the antiepileptic activity of these
      drugs. The purpose of this study was to determine the effects of these
      anticonvulsants on voltage-dependent calcium channels in pathologically altered
      neurons from patients with chronic temporal lobe epilepsy. METHODS: Acutely
      isolated human hippocampal granule cells were examined by using the whole-cell
      configuration of the patch-clamp technique. RESULTS: PHT and CBZ produced a
      reversible, concentration-dependent inhibition of high-voltage-activated (HVA)
      Ca2+ currents without affecting voltage-dependent activation. The concentration
      response curves of PHT and CBZ indicated maximal inhibition of 35 and 65%,
      respectively, with half-maximal inhibition being obtained at 89 and 244 microM,
      respectively. At therapeutic cerebrospinal fluid (CSF) concentrations, HVA
      currents were not significantly altered by PHT and CBZ. However, PHT but not CBZ
      showed a reduction of HVA currents of 16% at a therapeutic whole-brain
      concentration of 80 microM. In contrast to CBZ, PHT produced a small
      hyperpolarizing shift in the voltage dependence of steady-state inactivation.
      PHT, 80 microM, shifted the potential of half-maximal inactivation by -3.1 +/-
      0.5 mV (p < 0.05). GBP, which was recently found to bind to the alpha2delta
      subunit of a neuronal Ca2+ channel, showed no modulation of Ca2+ conductances.
      CONCLUSIONS: These results suggest that, in contrast to GBP and CBZ, modulation
      of postsynaptic Ca2+ channels can contribute to the anticonvulsant action of PHT
      in human hippocampal granule cells.

PMID- 9578026
TI  - Brain distortions in patients with primarily generalized tonic-clonic seizures.
AB  - PURPOSE: A precondition for the diagnosis of primarily generalized epilepsy with
      tonic-clonic seizures (GTCS) is absence of brain pathology. This definition,
      based on normal findings on computed tomography (CT) and magnetic resonance
      imaging (MRI) is challenged however, by observation of microscopic migrational
      disturbances in patients with GTCS. In the present study, we examined whether
      hitherto undiscovered gross manifestations of the reported migrational
      disturbances may be detected by analysis of CT and MRI scans with a computerized
      anatomic brain atlas. METHODS: The atlas program permitted group comparisons of
      size, intrinsic proportion, and shape of the brain. Healthy men (n = 20),
      patients with partial seizures (n = 8), secondarily generalized partial seizures
      (n = 8), and patients with GTCS (n = 10) were studied. The contours of the brain
      of the computerized atlas were first transformed and adjusted to the contours,
      central structures, and ventricles of each subject's MRI scans. During this
      process, the specific parameters for the shape, size, and proportion of the brain
      were determined, resulting in a set of values for each subject. These values were
      then applied for comparisons between the four investigated groups. RESULTS: In
      relation to the controls, patients with GTCS had brains significantly flattened
      in the craniocaudal direction (p = 0.002), with a disproportionally small caudal
      part. The anterior portion of their brain was also, relatively elongated as
      compared with the posterior portion (p = 0.04). Similar systematic abnormalities
      were not observed in patients with partial epilepsy. CONCLUSIONS: The observed
      deformations are compatible with previously reported findings of Purkinje cell
      degeneration and frontal lobe microdysgenesis in GTCS. The study suggests a new
      approach to identify effects of morphologic abnormalities in the brain when
      results of conventional structural neuroimaging are normal.

PMID- 9578027
TI  - Clinical usefulness of the dipole tracing method for localizing interictal spikes
      in partial epilepsy.
AB  - PURPOSE: To clarify the clinical usefulness of the dipole tracing method in
      evaluation of interictal EEG spikes in patients with partial epilepsy. METHODS:
      Eight patients with partial epilepsy were studied. We compared the generator
      source of interictal spikes detected by the dipole tracing method with the
      results of magnetic resonance imaging (MRI), interictal/ictal measurement of
      cerebral blood flow (CBF) by single photon emission computed tomography (SPECT),
      interictal measurement of glucose metabolism by positron emission tomography
      (PET) and invasive electrocorticogram (ECoG). RESULTS: In 5 patients with mesial
      temporal lobe epilepsy (TLE), including 3 patients who underwent standard
      temporal lobectomy, the dipole tracing method showed results consistent with
      those of other examinations and better correlation with ECoG than with other
      noninvasive examinations. In a patient with mesial TLE who had defects in the
      skull due to previous surgery, the dipoles were located more laterally than
      expected. In a patient with frontal lobe epilepsy (FLE) who was finally proved to
      have an epileptogenic area in the lateral frontal area, the spike dipoles were
      identified in the medial side of the frontal lobe. CONCLUSIONS: The dipole
      tracing method used in the present study is useful for localizing epileptogenic
      areas in patients with mesial TLE. However, in patients with partial skull
      defects and in those with FLE, the reliability of this method is still in
      accuracy of the lobe level.

PMID- 9578028
TI  - Characterization and comparison of local onset and remote propagated
      electrographic seizures recorded with intracranial electrodes.
AB  - PURPOSE: To compared the ictal discharge patterns between local onset and remote
      propagated electrographic seizures recorded with chronic intracranial electrodes.
      METHODS: The electrophysiological data from 88 consecutive patients who underwent
      chronic intracranial EEG monitoring were retrospectively reviewed. The early and
      late discharge patterns of electrographic seizures at local onset and distant
      propagated sites were determined by blinded visual inspection and computerized
      analysis. RESULTS: Four early and three late electrographic seizure patterns were
      observed at the local onset sites. The four early patterns consisted of a
      rhythmic discharge in the beta range ("beta buzz"), rhythmic alpha-theta
      activity, rhythmic sharp waves in the delta range, and an irregular spike
      discharge. The three distinct late-discharge patterns consisted of a late beta
      buzz, rhythmic sharp theta activity, and a rhythmic polyspike and wave discharge.
      At remote propagated sites, electrographic seizures could be divided into two
      different types according to their early discharge pattern. The first was unique
      to remote propagated electrographic seizures and consisted of a rhythmic theta
      delta activity correlated with the concurrent activity at the local-onset site.
      The second remote initiation type consisted of patterns indistinguishable from
      the earlier discharge patterns recorded at the local onset site. CONCLUSIONS: The
      initial ictal discharge pattern recorded with intracranial electrodes can assist
      in differentiating local onset and remote propagated electrographic seizures,
      with rhythmic round theta-delta activity being unique to distant propagated
      sites. Nevertheless, the initial discharge of a subclass of remote propagated
      electrographic seizures consists of an independent pattern indistinguishable from
      that observed at local onset sites.

PMID- 9578029
TI  - Selective amobarbital test for the determination of language function in patients
      with epilepsy with frontal and posterior temporal brain lesions.
AB  - PURPOSE: Selective amobarbital tests with selective temporary inactivation of the
      left frontal operculum and/or the left parietotemporal cortex were performed in 5
      patients with left-hemispheric epileptogenic lesions in or adjacent to classical
      Broca's and/or Wernicke's area. The aim was to assess language functions in these
      brain regions before surgery, to tailor the surgery according to the individual
      functional importance of these brain regions, and to predict postoperative
      outcome. METHODS: Amobarbital was injected by transfemoral selective
      catheterization of the arteries supplying the target areas. Along with
      neuropsychological and neurological testing during the amobarbital procedure, EEG
      recordings were performed in all patients, and [99mTc]HMPAO-single photon
      emission computed tomography (SPECT) in 2 patients. RESULTS: After the
      amobarbital injection into the left frontal opercular region, there was no
      recognizable language dysfunction in 3 patients. In these 3 patients, the lesions
      in or adjacent to the frontal operculum were completely resected without
      postoperative language impairment. In the remaining 2 patients, temporary
      language impairment after the amobarbital injection into the left frontoopercular
      and Wernicke's region, respectively, suggested language functions in these areas.
      Surgery was restricted to the left mesiotemporal lobe in 1 patient. In the other
      patient, the tumor infiltrating the frontal operculum was restrictively resected.
      Postoperatively, the first patient had no language impairment, but the latter had
      transient global aphasia, from which she recovered. CONCLUSIONS: Selective
      temporary amobarbital inactivation of brain regions that may be associated with
      language has clearly indicated the presence or absence of language functions in
      these regions. The test contributed substantially to planning of the surgical
      approach in each patient. The predictive value of the amobarbital test was
      demonstrated by the postoperative outcome.

PMID- 9578030
TI  - Functional plasticity after left anterior temporal lobectomy: reconstitution and
      compensation of verbal memory functions.
AB  - PURPOSE: This study investigated the functional plasticity of the brain to
      reconstitute and compensate for verbal memory functions after epilepsy surgery of
      left temporocortical and temporomesial structures. We hypothesized that memory
      outcome would be best when surgery is performed within the period of cerebral
      plasticity, and that the outcome should be worst when fluid intelligence starts
      to decrease with physiologic aging. We also raised the question of different
      plasticity and compensation mechanisms for temporomesial and temporocortical
      memory functions. METHODS: We evaluated preoperative and 1-year-postoperative
      memory data and other verbal functions in 104 patients with epilepsy, who
      underwent a standard left anterior temporal lobe resection. We used memory
      measures that had been previously shown to be most selective for mesial and
      lateral functions, respectively. Determinants of postoperative memory outcome
      were evaluated by multiple regression analysis. Group statistics were calculated
      on the basis of the periods that are usually assumed to be significant for
      plasticity and behavioral compensation. Individual postoperative changes in
      memory functions were evaluated on the basis of test-retest data obtained in a
      group of 100 nonsurgical patients with localization-related epilepsies (mean
      retest interval >12 months). RESULTS: Only changes in cortically represented
      learning and data acquisition were related to age, plasticity, and capacities for
      behavioral compensation. No patient in the youngest group (younger than 15
      years), 33% of patients who had surgery between the ages of 15 and 30 years, and
      61% of the patients undergoing surgery older than age 30 years had significant
      deterioration in verbal learning. In contrast, postoperative changes in
      temporomesial consolidation/retrieval processes were independent of age at the
      time of surgery, plasticity, and capacities for behavioral compensation.
      CONCLUSIONS: Our data indicate different time windows for the reconstitution and
      compensation of mesial and cortical aspects of memory. Whereas the reconstitution
      of and compensation for cortical functions appear restricted by decreasing
      plasticity and physiological aging, mesial functions seem to be reconstituted by
      contralateral mesial structures over a much longer period. Concerning drug
      resistant localization-related epilepsies, our results justify early
      consideration of surgery, especially when cortical structures are affected.

PMID- 9578031
TI  - Naming decline after left anterior temporal lobectomy correlates with
      pathological status of resected hippocampus.
AB  - PURPOSE: To evaluate the determinants of postoperative change in visual
      confrontation naming ability and the differential sensitivity of two common tests
      of confrontation naming. METHODS: In a group of 99 patients undergoing lobectomy
      of the left, language-dominant anterior temporal lobe, we examined naming ability
      using two measures: the 60 item Boston Naming Test (BNT), and the Visual Naming
      (VN) subtest of the Multilingual Aphasia Examination (MAE). ATL entailed
      resection of lateral temporal lobe followed by microsurgical complete removal of
      hippocampus. Language mapping was not performed. The status of the resected
      hippocampus was graded on a scale 0-4 of hippocampal sclerosis (HS). A
      dichotomous grouping HS- (grades 0 and 1, n = 34) and HS+ (grades 3 and 4, n =
      61) was effected. Age at surgery, age of epilepsy onset, sex, extent of lateral
      temporal resection, Full-Scale IQ (FSIQ), and preoperative naming scores were
      also examined as potential predictors of pre- versus postoperative naming change.
      RESULTS: Preoperative BNT and VN scores were significantly worse for HS+ than for
      HS- (BNT, p < 0.05; VN, p = 0.001). Postoperatively, BNT and VN scores
      significantly declined for HS- as compared with HS+ patients (p < 0.001). For
      individual risk, the 90th centile of reliable change index (RCI) was used. By
      this criterion, of the total sample, 39% evidenced decline on the BNT and 17%
      evidenced decline on the VN. Logistic regression analysis with backward
      elimination showed HS to be the only predictor of decline in BNT and HS and sex
      to be the only predictors of VN decline. Males were more at risk than females.
      Age, age at onset, extent of lateral resection, preoperative scores, and FSIQ
      were not predictors. Using age at onset as a proxy for HS+/HS- we calculated
      probabilities for naming decline for given onset age. CONCLUSIONS: Both
      preoperative and postoperative change in naming ability are associated with the
      pathological status of the hippocampus. The potential interpretations and
      implications of these findings are discussed.

PMID- 9578033
TI  - Nonepileptic posttraumatic seizures.
AB  - PURPOSE: Epileptic posttraumatic seizures (PTSs) are a well-recognized
      consequence of head injury (HI), but HI and nonepileptic seizures (NESs) have not
      been related. We describe a significant subset of patients with NESs who had
      their seizures attributed to HI. METHODS: We reviewed the records of all patients
      diagnosed with NES at the University of Maryland Medical Center over a 6-year
      period (1989-1995) and selected patients with seizures attributed to a head
      injury occurring < or =3 years before the onset of their seizures. RESULTS: Of
      157 patients with video-EEG confirmed NES, 37 (24%) had the onset of their
      seizures attributed to an HI. Their average age was 34 years (range, 15-56
      years); 68% were women. Nonepileptic PTS usually developed within the first year
      after HI (89%). Convulsive symptoms were present in 54%. Whereas epileptic PTSs
      characteristically follow severe HI, the majority (78%) of our patients with
      nonepileptic PTSs sustained only mild HI. Before their HI, 76% of our patients
      were employed, working in the home, or students, but only 11% could continue
      those activities after developing nonepileptic PTSs. CONCLUSIONS: Nonepileptic
      PTSs are frequently mistaken for epileptic PTSs and result in serious disability.
      The misdiagnosis of nonepileptic PTSs leads to ineffective and inappropriate
      treatment. Patients with intractable seizures after HIs, particularly mild HIs,
      should be carefully evaluated for NESs.

PMID- 9578032
TI  - Interictal cardiovascular autonomic responses in patients with epilepsy.
AB  - PURPOSE: To evaluate the interictal autonomic nervous system function in 84
      patients with epilepsy: 37 with newly diagnosed, previously untreated epilepsy,
      and 47 patients receiving long-term carbamazepine (CBZ), phenytoin (PHT), or
      valproate (VPA) monotherapy, or CBZ plus PHT, or CBZ plus VPA for their seizure
      disorder. METHODS: We assessed autonomic control of the cardiovascular regulatory
      system by standardized cardiovascular reflex tests measuring changes in heart
      rate (HR) and blood pressure (BP) at rest and after certain stimuli. RESULTS: The
      HR and BP responses were similar to those of control subjects in patients with
      newly diagnosed epilepsy. However, HR variation during normal breathing and
      maximum systolic BP increase in isometric work were diminished in patients, who
      had been treated with antiepileptic drugs (AEDs) for epilepsy for a long time.
      Diminished HR responses to the Valsalva maneuver were noted in patients receiving
      CBZ as monotherapy and during deep breathing in patients receiving CBZ combined
      with PHT or VPA. Furthermore, patients receiving CBZ had diminished BP responses
      in isometric work. When analyzed in relation to epilepsy type, suppressed HR
      responses in normal breathing were associated with primary generalized epilepsy
      (PGE), whereas diminished BP responses in isometric work were associated with
      partial epilepsy. Two patients with recently diagnosed partial epilepsy and 1
      patient receiving long-term CBZ monotherapy for partial epilepsy had two abnormal
      cardiovascular response test results. CONCLUSIONS: Our results show that
      cardiovascular responses mediated by both the parasympathetic and sympathetic
      nervous system are diminished in patients with epilepsy. However, the changes
      appear to be clinically significant in only a few of them and appear to be
      associated with CBZ medication. Further studies are needed to detect the
      underlying complex interactions and clinical significance of autonomic nervous
      system dysfunction in patients with epilepsy.

PMID- 9578034
TI  - Factors distinguishing families of patients with psychogenic seizures from
      families of patients with epilepsy.
AB  - PURPOSE: Psychogenic seizures (PS) (emotionally based nonelectrical seizures)
      have been explained by psychodynamics and trauma. However, the family health
      literature suggests that somatization, of which psychogenic seizures are a form,
      may run in families and be determined by family patterns of response to distress.
      This study compared families of patients with PS and those of patients with
      epilepsy on variables of distress (anxiety and depression) and somatization.
      METHODS: Eighteen patients (9 with PS and 9 with epilepsy) matched for age and
      education, and their families answered the Health Status Questionnaire (HSQ), the
      Weinberger Adjustment Inventory (WAI), the Family Emotional Involvement and
      Criticism Scale (FEICS), Barsky's Somatization Symptom Inventory (SS), and the
      Dissociation Experience Scale (DES). Family members' scores were averaged to
      obtain "family scores." RESULTS: Patients with PS and those with epilepsy did not
      differ in any of the measures. However, families of patients with PS reported
      more health problems, distress, and criticism than did families of patients with
      epilepsy (p < 0.05). Families of patients with PS had increased criticism and
      somatic problem scores comparable to those of both types of patients.
      CONCLUSIONS: Although epilepsy causes patients physical and emotional problems,
      their families are relatively healthy. In contrast, families of patients with PS
      are more troubled and may unwittingly contribute to PS through family distress,
      criticism, and tendencies to somatize.

PMID- 9578035
TI  - Complex partial status epilepticus in late-onset MELAS.
AB  - A patient with recurrent episodes of complex partial status epilepticus and a
      distinctive pattern of periodic lateralized epileptiform discharges (PLEDs) is
      presented. The patient was subsequently shown to have a mitochondrial disorder of
      the MELAS type, a hitherto unreported association. The case illustrates that CPSE
      should be added to the list of possible causes of acute neurological
      deterioration in MELAS patients.

PMID- 9578036
TI  - History of "epileptic vertigo": its medical, social, and forensic problems.
AB  - We traced the history of the association of vertigo with the condition of
      epilepsy through the ages. In ancient times, vertigo was closely linked with
      epilepsy; indeed, it was believed to be the harbinger of chronic seizures. With
      the advent of modern scientific study of epilepsy initiated by the French in the
      18th and 19th centuries, vertigo, not yet associated with disease of the inner
      ear or vestibular connections, assumed a specific role in the clinical gradation
      of seizure entities. It was believed to be the mildest form of epilepsy. Later,
      with the establishment of the conceptual linkage of "larval" or "masked" epilepsy
      with outbursts of violence, "epileptic vertigo" was considered the trigger for
      potentially lethal behavior and thus assumed a much-feared reputation. Evidence
      for this abounds in the medical, legal, and even the popular literature at the
      end of the 19th century. The role of vertigo and its epileptic associations
      occupied the attention of most of the pioneer workers in epileptology of that
      era, and it was finally agreed that as a symptom the inner ear rather than
      epilepsy underlay its causation. Even today, epilepsy and vertigo are
      conceptually associated, sometimes erroneously.

PMID- 9578038
TI  - The occurrence of drug-induced myopia as a transient side effect of topiramate.

PMID- 9578037
TI  - Ketogenic diet: a time-tested, effective, and safe method for treatment of
      intractable childhood epilepsy.

PMID- 9578039
TI  - Melatonin inhibits iron-induced epileptic discharges in rats by suppressing
      peroxidation.
AB  - PURPOSE: Intracortical injection of iron ion induces recurrent seizures and
      epileptic discharges in the electrocorticogram. This observation may be used as a
      model of posttraumatic epilepsy. The involvement of iron-mediated oxygen free
      radical species and neuronal lipid peroxidation in iron-induced seizure has been
      suggested. Melatonin exerts free radical scavenging properties. In this study, we
      examined the protective effect of melatonin against iron-induced seizures.
      METHODS: We examined the protective effect of melatonin against in vitro iron
      induced oxidative damage in homogenates from rat cerebral cortex, by measuring
      the concentration of thiobarbituric acid reactive substances (TBARS), as an index
      of oxidative damage. We also examined the effect of melatonin on the appearance
      of epileptic discharges in the EEG following injection of FeCl3 into the
      sensorimotor cortex in anesthetized rats, and by measuring the concentration of
      TBARS in the brain tissue. RESULTS: FeCl3 increased the concentration of TBARS in
      brain homogenates in a concentration-dependent manner, and melatonin reduced
      FeCl3-induced rise in TBARS in a dose-response fashion. Pretreatment with
      melatonin suppressed or delayed the development of FeCl3-induced epileptic
      discharges and decreased the concentration of TBARS in brain tissues.
      CONCLUSIONS: Our results suggest that iron ion generates oxygen free radical
      species that induce neuronal macromolecular peroxidation and seizure, and that
      melatonin inhibits iron-induced seizures by scavenging free radicals.

PMID- 9578040
TI  - MRS metabolic markers of seizures and seizure-induced neuronal damage.
AB  - PURPOSE: Proton magnetic resonance spectroscopy (MRS) was used to identify
      specific in situ metabolic markers for seizures and seizure-induced neuronal
      damage. Kainic acid (KA)-induced seizures lead to histopathologic changes in rat
      brain. The protective effect of cycloheximide treatment against neuronal damage
      caused by KA-induced seizures was studied, using in situ proton MRS imaging
      technique. METHODS: Rats were pretreated with placebo or cycloheximide 1 h before
      KA injection. Rat brains (n = 25) were scanned at the level of the hippocampus
      before, during, and 24 h after seizures. Spectra were recorded and the relative
      ratios of N-acetylaspartate (NAA), choline (cho), and lactate (Lac) to creatine
      (Cr) were calculated and compared between groups. RESULTS: A significant increase
      in Lac ratios was observed in KA-treated rats during and 24 h after seizure onset
      and this increase was prevented by cycloheximide pretreatment. NAA ratios were
      significantly higher during the ictal phase following KA treatment and this
      effect was not affected by cycloheximide pretreatment. Nissl staining confirmed
      previously reported prevention of KA-induced neuronal loss in CA3 and CA1 areas
      of the hippocampus by cycloheximide pretreatment. CONCLUSIONS: Our results
      suggest that in situ Lac increase is a marker of seizure-induced neuronal damage,
      whereas N-acetylaspartate (NAA) changes during and after status epilepticus may
      be a reflection of neuronal activity and damage, respectively.

PMID- 9578041
TI  - Comparison of effects of valproate and trans-2-en-valproate on different forms of
      epileptiform activity in rat hippocampal and temporal cortex slices.
AB  - PURPOSE: Reducing the extracellular magnesium or calcium or increasing the
      extracellular potassium induces different patterns of epileptiform activity in
      the hippocampus and the entorhinal cortex. Although in the low Ca2+ and K+
      models, seizure-like events (SLEs) develop in area CA1 of the hippocampus, only
      short recurrent discharges develop in the low Mg2+ model. In contrast, in low
      Mg2+, SLEs and late recurrent discharges (LRDs) are observed in the entorhinal
      cortex. METHODS: We compared the effects of valproate (VPA) and its major
      metabolite, trans-2-en-VPA (TVPA), on all these different model activities using
      extracellular field potential measurements. We also investigated the
      equilibration time course of VPA in the slice by using VPA-sensitive
      microelectrodes. RESULTS: Both drugs reversibly blocked most forms of
      epileptiform activity. The only exception was the LRDs in the entorhinal cortex.
      In paired experiments, TVPA appeared to be more effective than VPA bath applied
      with the same concentration to the same slice. With our measurements of the VPA
      concentrations in slices, we showed that the concentrations used were close to
      therapeutic drug levels. CONCLUSIONS: If TVPA stands the toxicological tests, it
      might be a useful alternative in the treatment of seizures.

PMID- 9578042
TI  - Intracranial EEG seizure-offset termination patterns: relation to outcome of
      epilepsy surgery in temporal lobe epilepsy.
AB  - PURPOSE: Studies using stereo-EEG (SEEG) and electrocorticography (ECoG) should
      not only identify a patient's epileptogenic zone, but also should provide
      prognostic information for surgical outcome. In this respect, seizure-offset
      patterns have so far been the subject of only one study, in which they were shown
      to be associated with poor outcome when recorded over cortical areas outside the
      temporal lobe of seizure onset. To clarify whether seizure-offset patterns are
      reliable in predicting seizure outcome, we studied SEEG/ECoG in a similar group
      of patients with temporal lobe epilepsy (TLE). METHODS: SEEG/ECoG records of 44
      patients with refractory TLE were analyzed. The areas of seizure termination were
      classified as ipsilateral or contralateral (mesial and/or lateral) temporal,
      (temporal and) frontal, and diffuse/bilateral. Patients were classified with
      respect to seizure outcome as either seizure-free (UCLA class 1a) or not seizure
      free (UCLA class 2-4); both groups were correlated with specific seizure-offset
      categories using Fisher's exact probability test and analysis of variance
      (ANOVA). RESULTS: Of the 44 patients, the majority (n = 36) had at least part of
      their seizure offsets in the ipsilateral temporal lobe, whereas 8 patients
      manifested no seizure offsets in this lobe. Only 9 patients (20%) showed
      exclusive offsets in the ipsilateral temporal lobe. No statistically significant
      difference was evident between patients with all seizure offsets in the
      ipsilateral temporal lobe and those with offsets elsewhere. Similarly, no
      statistically significant difference was evident between patients with a diffuse
      seizure offset and those with seizure offsets of a different category.
      CONCLUSIONS: Seizure-offset patterns in SEEG/ECoG are unreliable in predicting
      seizure outcome after resective activity surgery for TLE.

PMID- 9578043
TI  - Proton magnetic resonance spectroscopic imaging in patients with extratemporal
      epilepsy.
AB  - PURPOSE: Reduced levels of N-acetylaspartate (NAA) in temporal lobes responsible
      for temporal lobe epilepsy have been observed consistently in proton magnetic
      resonance spectroscopy (MRS) studies. METHODS: We investigated the potential of
      proton MRS to detect low NAA outside of the temporal lobes in patients with non
      lesional partial extratemporal epilepsy. Proton MR spectroscopic imaging (MRSI)
      data of both frontal lobes and central/postcentral regions were obtained in 20
      such patients and 16 normal control subjects. The epileptogenic region was
      determined by an extensive clinical-EEG investigation, including the recording of
      habitual seizures in each patient, and intracranial EEG recordings in 10
      patients. RESULTS: The relative NAA resonance intensities (i.e.,
      NAA/phosphocreatine plus creatine (CR(t)), NAA/choline-containing metabolites
      (Cho(t)) and NAA/Cr(t) + Cho(t)), were all significantly reduced throughout the
      spectroscopic image as compared with that of the controls. Furthermore, reduction
      of the NAA ratios was greater in the epileptogenic region as compared with the
      nonepileptogenic regions, on EEG investigation. CONCLUSIONS: In vivo proton MRSI
      of patients with nonlesional partial extratemporal epilepsy detected evidence of
      widespread neuronal damage or dysfunction that was greatest in the region of
      seizure focus.

PMID- 9578044
TI  - Pharmacokinetic evaluation of twice-daily extended-release carbamazepine (CBZ)
      and four-times-daily immediate-release CBZ in patients with epilepsy.
AB  - PURPOSE: A new capsule dosage form of carbamazepine (CBZ) has been developed,
      consisting of three different types of beads (immediate-release, extended
      release, and enteric-release) that may be taken sprinkled on food or swallowed
      for easy administration. We compared the pharmacokinetics of the extended-release
      dosage form of CBZ (Carbatrol capsules) twice daily with the conventional
      immediate-release formulation of CBZ four times daily. METHODS: The randomized,
      double-blind, two-way, cross-over study was conducted at two sites, with a
      planned sample size of 24 adult patients with epilepsy. Each treatment was
      administered for 2 weeks. At the end of the 2-week period, blood samples were
      obtained hourly for a 24-h period. RESULTS: The 90% confidence intervals (CI) of
      the ratio of the means of the extended-release formulation twice daily to the
      immediate-release formulation four times daily were within the range of 0.80-1.25
      for each of the pharmacokinetic parameters for CBZ and for the summation of CBZ
      and CBZ-epoxide (CBZ-E). There was no difference in the frequency of seizures
      between treatment (p = 0.103). CONCLUSIONS: Our results demonstrate that extended
      release CBZ twice daily was bioequivalent to immediate-release CBZ four times
      daily, with regard to CBZ levels and summation of CBZ and CBZ-E levels, based on
      the pharmacokinetic parameters evaluated. Substituting one formulation for the
      other did not cause patients to have a significant change in seizure frequency.

PMID- 9578046
TI  - Comparison of single- and repeated-dose pharmacokinetics of diazepam.
AB  - PURPOSE: To determine whether repeat boluses of diazepam (DZP) lead to
      significant accumulation in the central nervous system and/or peripheral
      compartments, as repeat intravenous boluses of diazepam are commonly used in the
      treatment of status epilepticus (SE). METHODS: In a rat model that permits
      simultaneous serum and cerebrospinal fluid (CSF) sampling, we characterized the
      pharmacokinetics of DZP and its metabolite, desmethyldiazepam, in CSF and blood
      using HPLC. DZP was administered by intraperitoneal injection as either a single
      dose (20 or 30 mg/kg) or repeat doses (10 or 20 mg/kg x 3, 1 h apart). RESULTS:
      After a single intraperitoneal dose, DZP was rapidly absorbed with a time to
      maximum concentration of 10 min. The serum concentrations then declined
      biexponentially. DZP rapidly entered the CSF, the CSF to serum ratio reached
      equilibrium within 10 min, and was equivalent to the ratio of free to total serum
      concentration. Repeated DZP dosing resulted in a threefold decrease in volume of
      distribution and clearance (p < 0.001). This was reflected in the CSF
      concentration data; however, after the third dose, the ratio of CSF to serum
      concentration, also increased greatly, representing further persistence of DZP in
      the CSF compartment. CONCLUSIONS: Repeat dosing of DZP leads to substantial
      accumulation, and high, persistent serum and CSF concentrations, which may
      explain the toxic effects of repeat DZP dosing. Repeat dosing of DZP using a
      tapering protocol, however, may increase the effectiveness of DZP in treating SE
      by preventing relapses without substantially increasing toxicity.

PMID- 9578045
TI  - Aggressive behaviour in intellectually challenged patients with epilepsy treated
      with lamotrigine.
AB  - PURPOSE: Lamotrigine (LTG) is a valuable addition to the medical management of
      epilepsy with wide spectrum of efficacy and good outcomes for quality of life. We
      report the emergence of a syndrome of aggressive behavior provoked by LTG in
      patients with epilepsy and intellectual challenge. METHODS: On recognition of a
      tendency to aggression in intellectually challenged patients whose epilepsy was
      treated with LTG, a survey was conducted of those from centers specializing in
      management of patients with intellectual disability who were treated with LTG.
      Responses to LTG were sought and patient's behavioral profiles were determined.
      RESULTS: Nineteen patients were identified (16 men, 3 women, aged 17-54 years).
      Five patients discontinued LTG due to unprovoked aggressive behavior subsequent
      to its use; 2 had aggressive behavior sufficient to justify discontinuation of
      LTG but required reintroduction to control the epilepsy; 1 required reduction in
      LTG dosage; 1 had aggression that responded to psychiatric intervention; and 1
      had aggression unrelated to LTG. Four patients had behavioral problems other than
      aggression, 4 had no change in behavior, and the behavior of 1 was improved by
      LTG treatment. CONCLUSIONS: LTG may provoke aggressive behavior and violence in
      intellectually handicapped patients with epilepsy, which may limit its use in
      such patients. Acknowledgment of the potential for such disturbance justifies
      greater surveillance of these patients and early discontinuation of LTG if
      necessary.

PMID- 9578047
TI  - Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics.
AB  - PURPOSE: To determine whether buccal/sublingual administration of midazolam (MDL)
      would lead to detectable venous concentrations and EEG changes in 10 healthy
      volunteers. METHODS: The study consisted of an open-label and a double-blind
      phases. Subjects held 10 mg MDL in 2 ml peppermint-flavored fluid or peppermint
      flavored placebo in their mouth for 5 min and then spat it out. Cardiorespiratory
      and EEG monitoring was performed in all subjects. RESULTS: Venous MDL
      concentrations measured on 10 occasions from 5 to 600 min after administration
      showed a rapid increase for the first 20-30 min. However, changes in the 8- to 30
      Hz frequencies identified by spectral analysis of the EEG showed changes in < or
      = 5-10 min in test but not in control subjects--more rapid than were expected
      from the venous absorption data. There were no significant adverse effects.
      CONCLUSIONS: Our data provide direct evidence of the speed of cerebral effect of
      a drug. Our results suggest that the buccal/sublingual route of administration
      should be tested in emergency treatment of seizures as an alternative to the
      rectal route, over which it has clear practical advantages.

PMID- 9578048
TI  - Occipital lobe seizures as the major clinical manifestation of reversible
      posterior leukoencephalopathy syndrome: magnetic resonance imaging findings.
AB  - PURPOSE: Reversible posterior leukoencephalopathy syndrome (RPLS) is an
      increasingly recognized brain disorder most commonly associated with malignant
      hypertension, toxemia of pregnancy, or the use of immunosuppressive agents. When
      associated with acute hypertension, RPLS typically occurs concurrently with the
      fulminant clinical syndrome of hypertensive encephalopathy. We describe occipital
      lobe seizures, in the setting of only moderate elevations of blood pressure, as
      the major clinical manifestation of RPLS. METHODS: Two patients from the Dent
      Neurologic Institute are presented with clinical and magnetic resonance imaging
      (MRI) correlation. RESULTS: New onset secondarily generalized occipital seizures
      were noted, with MRI findings consistent with RPLS. Both of the patients had
      chronic renal failure and a moderate acute exacerbation of chronic hypertension.
      Other features of hypertensive encephalopathy were lacking, such as headache,
      nausea, papilledema, and an altered sensorium. Magnetic resonance imaging (MRI)
      showed edematous lesions primarily involving the posterior supratentorial white
      matter and corticomedullary junction, consistent with RPLS. With lowered blood
      pressure, the MRI lesions resolved and the patients became seizure-free without
      requiring chronic anticonvulsant therapy. CONCLUSIONS: Occipital seizures may
      represent the only major neurologic manifestation of RPLS due to acute
      hypertension, especially in patients with renal failure. Other evidence of
      hypertensive encephalopathy, such as cerebral signs and symptoms, need not be
      present. Blood pressure elevations may be only moderate. Early recognition of
      this readily treatable cause of occipital seizures may obviate the need for
      extensive, invasive investigations. Despite the impressive lesions on MRI, prompt
      treatment of this disorder carries a favorable prognosis.

PMID- 9578049
TI  - Celiac disease, bilateral occipital calcifications and intractable epilepsy:
      mechanisms of seizure origin.
AB  - PURPOSE: To elucidate the mechanisms of seizure origin in patients with celiac
      disease and bilateral occipital calcifications (CEBOC). Individuals with CEBOC
      frequently present with occipital lobe seizures, but additional lesions and
      additional attack patterns may occur. METHODS: We studied two men and one woman
      who had CEBOC. Villous atrophy was revealed in the two patients who underwent
      duodenal biopsy. All had a comprehensive presurgical evaluation, including
      prolonged video-EEG recordings. Two had magnetic resonance imaging (MRI) with
      volumetric study of mesial temporal structures (MRIV). One patient had undergone
      stereotactic intracranial depth electrode studies (SEEG). RESULTS: All patients
      presented with intractable complex partial seizures. Two had partial simple
      seizures with visual aura. Neurologic examination was normal; one was of normal
      intelligence, and two were mildly retarded. Neuroimaging studies showed that each
      had bilateral occipital calcifications as well as epileptiform abnormalities over
      temporal lobes. In one, MRI showed an additional right frontal lesion, but SEEG
      demonstrated right occipital lobe seizure origin with anterior spread; this male
      patient later underwent a right occipital lobe resection. Another with a history
      of prolonged febrile convulsions had bilateral hippocampal and amygdalar atrophy
      demonstrated by MRIV. CONCLUSIONS: In one patient, SEEG confirmed that seizures
      originated in the occipital lobe. The presence of dual pathology was demonstrated
      in another, raising the possibility of both occipital and temporal seizure onset.
      The presence of extraoccipital lesions or of mesial temporal atrophy requires
      SEEG for clarification of seizure onset. In the absence of confounding factors
      and when laterality can be demonstrated, surgical treatment may be considered.

PMID- 9578050
TI  - Ganglioglioma and intractable epilepsy: clinical and neurophysiologic features
      and predictors of outcome after surgery.
AB  - PURPOSE: To review the clinical, neurophysiologic, and radiological data of
      patients with ganglioglioma who had undergone evaluation and surgery in our
      Epilepsy Program. METHODS: The medical and neurophysiologic records of 38
      patients with intractable epilepsy and ganglioglioma were reviewed. Data
      underwent statistical analysis. RESULTS: There were 28 temporal and 10
      extratemporal resections, with a mean age at seizure onset of 10.5 years and mean
      age at surgery of 22 years. Five tumor resections performed earlier were
      recorded. Twenty-nine patients had auras and 20 had secondarily generalized
      seizures. All 28 patients with temporal tumor had complex partial seizures.
      Preoperative MRI demonstrated the tumor in 36 of 36 patients: 17 of 29
      demonstrated gadolinium enhancement, and 17 of 36 had mass effect. Scalp
      interictal sharp waves were present in 32 patients, and in 15 they were
      multiregional. In two patients, scalp EEG seizure onset was from the hemisphere
      contralateral to the tumor. Postoperatively, 79% of patients (30 of 38) were
      seizure-free (Engel's class I) at 6 months, 72% at 1 year (26 of 36), and 63% at
      2 years (20 of 32). Excellent outcome was associated with a lower age at
      operation (p = 0.008), shorter duration of epilepsy (p = <0.01), absence of
      generalized seizures (p = <0.01), and no epileptiform discharges on a
      postoperative EEG (p = 0.01). CONCLUSIONS: Good surgical outcome is expected in
      patients with ganglioglioma despite years of medically resistant seizures. Good
      outcome may be achieved despite EEG findings that may conflict with tumor
      location, and is more likely when surgery is performed relatively soon after
      epilepsy onset.

PMID- 9578052
TI  - Contribution of neuropsychological data to the prediction of temporal lobe
      epilepsy surgery outcome.
AB  - PURPOSE: We empirically examined the contribution of neuropsychological data to
      the prediction of postoperative seizure control relative to base rate information
      in an existing series of patients undergoing anterior temporal lobectomy (ATL).
      METHODS: A discriminant function predicting surgery outcome (seizure-free vs. non
      seizure-free) was computed separately for samples of patients with left (n = 79)
      and right (n = 62) temporal lobectomy (LATL, RATL). Predictor variables included
      14 measures tapping five neurocognitive domains. The predicted base rates were
      compared with the actual base rates in the two samples. Finally, overall
      predictive accuracy was examined in optimal versus suboptimal ATL patients.
      RESULTS: The base rate of seizure freedom in the LATL group was 74.70%; that in
      the RATL group was 66.10%. The predictive function for the LATL group achieved a
      hit rate of 80.00% and a positive predictive power of 92.11%. The function for
      the RATL group achieved a hit rate of 83.33% and a positive predictive power
      (PPP) of 89.66%. The overall predictive accuracy for the optimal group was only
      55%, but that in the suboptimal group was 72%. CONCLUSIONS: Neuropsychological
      data used in a multivariate statistical fashion may be able to offer an
      incremental increase in the prediction of postoperative seizure freedom relative
      to existing base rates of surgery success in patients with ATL epilepsy. The use
      of neuropsychological data may be of greatest predictive value in a population of
      ATL candidates with suboptimal findings with a lower base rate of postoperative
      seizure freedom, but may actually reduce predictive accuracy in a group of ATL
      candidates from an optimal population with an already high base rate of surgical
      success.

PMID- 9578051
TI  - Does presurgical IQ predict seizure outcome after temporal lobectomy? Evidence
      from the Bozeman Epilepsy Consortium.
AB  - PURPOSE: Considerable debate exists concerning whether the presence of low
      preoperative IQ should be a contraindication for focal resective epilepsy
      surgery. METHODS: We examined the relationship between baseline IQ scores and
      seizure outcome in 1,034 temporal lobectomy cases from eight epilepsy surgery
      centers participating in the Bozeman Epilepsy Consortium. RESULTS: Those patients
      who continued to have seizures following surgery had statistically lower
      preoperative IQ scores than those who were seizure-free (p < 0.009), but only by
      2.3 points. This small but statistically significant relationship was fairly
      robust; it was observed across seven of the eight centers, and indicates that the
      findings can be generalized. Among patients with IQ scores of < or = 75, 32.8%
      continued to have seizures following surgery, whereas 23.8% and 16.9% were not
      seizure-free when IQ scores were between 76 and 109 and > or = 110, respectively.
      Relative risk analyses revealed no significant increase in risk among patients
      with low IQ scores who had no structural lesions other than mesial temporal
      sclerosis. However, patients with IQ scores of < or = 75 had nearly a fourfold
      (390%) increase in risk for continued seizures as compared with those with higher
      IQ scores if structural lesions were present. CONCLUSIONS: While our results
      suggest that preoperative IQ scores alone are not good predictors of seizure
      outcome and should not be used to exclude patients as potential surgical
      candidates. IQ scores can be useful for counseling patients and their families
      concerning the relative risks of surgery.

PMID- 9578053
TI  - Do males 30-50 years of age with chronic epilepsy and on long-term anticonvulsant
      medication have lower-than-expected risk of developing coronary heart disease?
AB  - PURPOSE: It has been claimed that long-term use of antiepileptic drugs (AEDs)
      brings about changes in the lipid profile which might resist development of
      cardiovascular disease. The aim of this study was to test the following
      hypothesis: Do males with chronic epilepsy and on long-term treatment with AEDs
      have a lower than expected risk of developing coronary heart disease? METHODS:
      The coronary risk profile in 40 male patients with chronic epilepsy, aged 30-50
      years, was explored, using an American individual coronary risk factor test
      program (the Cooper test). We made a survey of the patients' risk factors: total
      cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, glucose,
      blood pressure, body fat percentage, physical fitness, hereditary factors,
      smoking habits, and degree of stress. Each factor was given a score, and the sum
      of scores constituted the total coronary risk profile. Eighty men in the same age
      group, casually selected from an industrial medical service, served as controls.
      RESULTS: There was no statistically significant difference in the total coronary
      risk profile between the epilepsy patients and the controls. Nor were there any
      significant differences among the individual risk factors except for physical
      fitness level, which was significantly lower among the epilepsy group than among
      the controls. In the epilepsy group, however, there was a trend toward higher
      levels of total cholesterol, higher levels of HDL-cholesterol, lower levels of
      total cholesterol/HDL-cholesterol ratio, increased body fat percentage, greater
      heredity and somewhat greater coronary risk score as compared with the healthy
      controls, but the differences did not reach statistical significance. The
      protective effect against coronary heart disease exercised by the enzyme-inducing
      AEDs seems to be counteracted by other factors, like reduced physical fitness and
      increased body fat percentage. CONCLUSIONS: Our hypothesis was not confirmed,
      because we found that the 40 patients with chronic epilepsy tested had about the
      same risk of developing coronary heart disease as did the control group.

PMID- 9578054
TI  - Familial occurrence of epilepsy in children with newly diagnosed multiple
      seizures: Dutch Study of Epilepsy in Childhood.
AB  - PURPOSE: To study the familial occurrence of epilepsy in children with newly
      diagnosed multiple unprovoked seizures. METHODS: Between August 1988 and
      September 1992, 462 children with two or more unprovoked seizures were included
      in the prospective Dutch Study of Epilepsy in Childhood. Seizures and epilepsy
      syndromes of probands were classified according to the International
      Classifications. Probands with at least 1 first-degree relative with epilepsy
      were selected. Seizures and syndromes of their relatives were classified using
      medical files and telephone interviews. RESULTS: In 42% of the probands, the
      epilepsy was classified as localization-related, in 57% as generalized, and in 1%
      as undetermined whether focal or generalized. The 47 (10.2%) children with at
      least 1 first-degree relative with epilepsy less frequently had localization
      related epilepsy (23%) and more often had generalized epilepsy (77%) as compared
      with the total group of probands. Fifty-eight first-degree and 21 other relatives
      had epilepsy. Thirty-three of the 40 (83%) first-degree relatives with idiopathic
      or cryptogenic epilepsy had the same seizure type as the proband, but detailed
      information about their seizures was sometimes difficult to obtain. Of the 12
      first-degree relatives with epilepsy syndromes classifiable according to the
      International League Against Epilepsy (ILAE) 7 (58%) had the same syndrome as the
      proband. CONCLUSIONS: In 10% of children with newly diagnosed epilepsy, the
      condition is familial. Relatively more often, these children have generalized
      epilepsy syndromes as compared with children with a negative family history. Most
      of the relatives with idiopathic or cryptogenic epilepsy had the same seizure
      type as the proband. These findings confirm the role of genetic factors in the
      pathogenesis of epilepsy.

PMID- 9578056
TI  - Efficacy and toxicity of sequential high-dose therapy with peripheral blood stem
      cell support in patients with high-risk breast cancer.
AB  - Patients with high-risk breast cancer may benefit from dose-escalated
      chemotherapy. We studied toxicity and therapeutic efficacy of sequential high
      dose therapy consisting of two cycles of ifosfamide 12,000 mg/m2, carboplatin 900
      mg/m2, and epirubicin 180 mg/m2 (ICE) with peripheral blood stem cell support.
      Ninety-one patients with advanced breast cancer were included. Fifty-one patients
      with stage II/III disease and 10 or more tumor-positive axillary lymph nodes
      received high-dose therapy as adjuvant treatment; the remaining 40 patients were
      treated for metastatic disease. Peripheral blood stem cells were collected
      following granulocyte colony-stimulating factor-supported induction chemotherapy.
      In 68 patients, induction chemotherapy included two cycles of ifosfamide 7,500
      mg/m2 and epirubicin 120 mg/m2, while 23 patients received one cycle of
      paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 135 mg/m2,
      ifosfamide 6,000 mg/m2, and epirubicin 90 mg/m2. One hundred ninety-two cycles of
      ICE were supported with a median of 3.5 x 10(6) CD34+ cells/kg body weight
      (range, 1.7 to 38 x 10(6) CD34+ cells/kg body weight), which resulted in rapid
      hematologic reconstitution with recovery times, for a median neutrophil count of
      0.5 x 10(9)/L of 13 days (range, 6 to 20 days) and for a median platelet count
      greater than 20 x 10(9)L of 9 days (range, 5 to 24 days). Seven patients received
      only one cycle of ICE because of progressive disease (in two patients with
      metastatic disease), central nervous system toxicity (one patient), cardiac
      toxicity (one patient), severe enterocolitis (one patient), development of human
      leukocyte antigen antibodies (one patient), and wish to withdraw from the study
      (one patient). Seventeen patients with metastatic disease received an additional
      high-dose cycle consisting of the non-cross-resistant agents thiotepa 600 mg/m2,
      etoposide 1,500 mg/m2, and paclitaxel 165 mg/m2. In patients treated adjuvantly,
      the probability of disease-free survival was 64% at 47 months, which compares
      favorably with results of conventional treatment protocols, with a 47% event-free
      probability at the same time period. The probability of progression-free survival
      in patients with metastatic disease was 18% at 44 months. In conclusion,
      sequential high-dose therapy with peripheral blood stem cell support in patients
      with high-risk breast cancer can be administered safely and offers a potential
      benefit in the adjuvant setting.

PMID- 9578055
TI  - Defining the role of novel high-dose chemotherapy regimens for the treatment of
      high-risk breast cancer.
AB  - We have explored several novel high-dose combinations in an attempt to increase
      antitumor activity while decreasing treatment-related toxicity. From October 1989
      through June 1997, we performed phase I/II dose-escalation trials exploring novel
      high-dose regimens including ifosfamide/carboplatin/etoposide,
      mitoxantrone/thiotepa, and paclitaxel (Taxol; Bristol-Myers Squibb Company,
      Princeton, NJ)/mitoxantrone/thiotepa. We have also evaluated
      busulfan/cyclophosphamide and cyclophosphamide/thiotepa/carboplatin in phase II
      trials. Three hundred ninety-three patients have been treated in these trials and
      followed for a minimum of 3 months. Event-free survival (including relapses and
      treatment-related mortality; +/-SE) at 3 years by stage and chemosensitivity is
      as follows: stage II, four to nine positive nodes (n=16), 52%+/-17%; stage II,
      greater than nine nodes (n=30), 46%+/-11%; stage III (n=59), 50%+/-8%;
      inflammatory stage III (n=15), 27%+/-17%; stage IV, anthracycline responsive
      (n=69), 19%+/-5%; stage IV, anthracycline refractory but responsive to salvage
      therapy with ifosfamide, carboplatin, and etoposide or paclitaxel (n=53), 12%+/
      6%; stage IV, refractory (n=128), 5%+/-2%; and stage IV, not evaluable for
      response (n=23), 10%+/-8%. Treatment-related mortality was 4% for both phase I
      and II studies involving stage II breast cancer patients, 5% for stage III breast
      cancer, 15% for inflammatory breast cancer, and 18% for all stage IV breast
      cancers, responsive and refractory. We conclude that high-dose therapy for the
      treatment of high-risk early stage breast cancer or metastatic breast cancer
      results in durable remissions. Chemosensitivity to induction regimens remains the
      most important prognostic indicator, although long-term survival has been seen
      even in patients with highly refractory disease. Further studies are necessary to
      define optimal high-dose strategies based on stage and chemosensitivity of
      disease.

PMID- 9578057
TI  - Dose intensity in small cell lung cancer.
AB  - Evidence from preclinical models and from clinical trials describing the
      importance of dose intensity in securing a better treatment outcome is reviewed.
      Recent randomized trials have shown statistically significant survival benefits
      with higher-dose, accelerated chemotherapy regimens with and without granulocyte
      colony-stimulating factor and granulocyte-macrophage colony-stimulating factor.
      The novel use of peripheral blood progenitor cells contained in whole blood
      autotransfusions, which allow a marked increase in dose intensity of an
      ifosfamide/carboplatin/etoposide regimen, could provide a much easier method of
      delivering dose-intensive chemotherapy than previously available.

PMID- 9578058
TI  - High-dose therapy for adult soft tissue sarcoma: dose response and survival.
AB  - The role for high-dose therapy in the treatment of sarcomas is controversial and
      limited. Numerous trials in soft tissue sarcomas have suggested dose-response
      relationships for doxorubicin (and epirubicin) and ifosfamide. Low doses of these
      agents are associated with lower response rates than aggressive doses that do not
      require cellular support. There is little evidence that doses high enough to
      require hematopoietic stem cell support achieve higher response rates. Complete
      responses remain rare, and no survival advantage has been documented. New drugs
      are needed urgently, particularly those with dose-response relationships and
      those achieving complete responses. In their absence, transplant therapy does not
      yet play a role in the treatment of soft tissue sarcomas, although further phase
      II trials could be performed to assess consolidation therapy for complete
      responders, patients requiring neoadjuvant therapy, and those with resectable
      oligometastatic disease. High-dose therapy has been evaluated more extensively in
      patients with pediatric histologies like Ewing's sarcoma, rhabdomyosarcoma, and
      osteosarcoma. Many more agents suited to transplant regimens have substantial
      activity against these histologies. Results from certain trials demonstrate
      improved, long-term, relapse-free survival compared with historical controls,
      whereas others suggest that selection biases may account for such "improvements."
      Development of new agents is needed. Carefully designed randomized trials to
      evaluate the role of high-dose therapy with cellular support should be strongly
      encouraged in these histologies.

PMID- 9578059
TI  - The use of dose-intensified chemotherapy in the treatment of metastatic
      nonseminomatous testicular germ cell tumors. German Testicular Cancer Study
      Group.
AB  - With the use of a cisplatin-based chemotherapy, metastatic testicular cancer has
      become a model for a highly curable malignant disease. Current data show that 70%
      to 80% of patients with this disease will achieve long-term survival following
      cisplatin/etoposide/bleomycin therapy. The role of high-dose chemotherapy with
      autologous stem cell support is being investigated in metastatic germ cell cancer
      in attempts to improve outcome for patients whose disease relapses after standard
      dose chemotherapy and for those who present initially with advanced metastatic
      disease. Prognostic categories for patients receiving high-dose salvage
      chemotherapy have recently been developed: cisplatin-refractory disease, beta
      human chorionic gonadotropin values greater than 1,000 U/L, and primary
      mediastinal germ cell tumors are factors characterizing patients who will derive
      less benefit from high-dose chemotherapy than those with chemosensitive disease
      at relapse. While standard-dose salvage chemotherapy achieves only a 20% long
      term survival rate, high-dose salvage chemotherapy may yield a cure rate of
      approximately 40%. A randomized study comparing high-dose therapy with
      conventional-dose therapy (IT94 coordinated by the European Group for Blood and
      Marrow Transplantation) in patients with relapsed disease is ongoing to
      substantiate this observation. The use of dose-intensive therapy as first-line
      treatment is currently being studied by several institutions. High-dose therapy
      may be better tolerated when used first line compared with its use in the salvage
      situation, and may also achieve a rapid initial cell kill before cytostatic drug
      resistance develops. The German Testicular Cancer Study Group has developed a
      sequential high-dose combination regimen of cisplatin/etoposide/ifosfamide given
      with granulocyte colony-stimulating factor and peripheral blood stem cell support
      for four cycles every 3 weeks. This ongoing study, started in 1990, had accrued
      218 patients with advanced testicular germ cell tumors as of June 1997. Of 141
      evaluable patients receiving dose levels 1 through 5, 82 (58%) have achieved
      complete remission with no evidence of disease and 32 (23%) have achieved partial
      remission with marker normalization. The early death rate was 8%. Overall and
      event-free survival rates at 2 years are 78% and 73%, respectively, with a
      projected 5-year overall survival rate of 74%. Despite favorable preliminary
      results, this approach cannot be considered standard treatment. Currently, high
      dose chemotherapy with peripheral blood stem cell transplantation should be
      administered to patients with testicular cancer only within controlled clinical
      trials to allow long-term cure rates and treatment-related late side effects to
      be evaluated.

PMID- 9578060
TI  - Additional chemotherapy agents improve treatment outcome for children and adults
      with advanced B-cell lymphomas.
AB  - We report the updated results of an intensive treatment protocol for children (<
      18 years) and adults (> or = 18 years) with advanced B-cell lymphomas. The
      protocol consists of two chemotherapy regimens: A, consisting of
      cyclophosphamide, doxorubicin, vincristine and high-dose methotrexate (CODOX-M),
      and B, consisting of ifosfamide, etoposide, and high-dose cytarabine (IVAC). Both
      cycles included intrathecal chemotherapy (cytarabine or methotrexate). Patients
      received a total of four cycles in the following sequence: A, B, A, B. Sixty-six
      previously untreated patients, enrolled before October 1996, were included in the
      present analysis. Of these, 55 had Burkitt's or Burkitt's-like lymphoma and 11
      had diffuse large B-cell lymphoma. There were 53 males ad 13 females; 40 were
      children and 26 were adults (age range, 3 to 57 years). To date, 61 patients have
      achieved a complete response to therapy. Two patients subsequently relapsed, but
      one of these is a long-term survivor after further therapy and a bone marrow
      transplant. The event-free survival rate is 85% at I year and beyond. The median
      potential follow-up period is 48 months (range, 12 to 96 months) for patients
      remaining in complete remission. Neutropenia occurred in 98% of cycles and
      infection in 46% of A cycles and 50% of B cycles, but the duration was shortened
      in B cycles by the administration of granulocyte colony-stimulating factor.
      Positive blood cultures were observed in 21% of A cycles and 28% of B cycles, and
      there have been three toxic deaths. These results are better than those achieved
      with an earlier version of CODOX-M, suggesting that the addition of the IVAC
      regimen is responsible for the improved results. The similarity of the outcome in
      children and adults, however, confirms our previous observation that, at least in
      adults younger than 60 years with Burkitt's or Burkitt's-like lymphomas,
      treatment with regimens similar to those used in children is warranted.

PMID- 9578061
TI  - Role of paclitaxel, ifosfamide, and cisplatin in patients with recurrent or
      metastatic squamous cell carcinoma of the head and neck.
AB  - This phase I/II study investigated the efficacy and toxic effects of combination
      chemotherapy using paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton,
      NJ), ifosfamide, and cisplatin (TIP) in patients with recurrent or metastatic
      squamous cell carcinoma of the head and neck. Twelve patients were entered in the
      phase I part of the study, results of which were reported previously. Fifty-three
      patients were treated in the phase II part of the study with 175 mg/m2 paclitaxel
      in a 3-hour infusion on day 1; 1,000 mg/m2/d ifosfamide in a 2-hour infusion on
      days 1 to 3; and 60 mg/m2 cisplatin on day 1, repeated every 3 to 4 weeks. Thirty
      five men and 18 women were treated; the median age was 55 years (range, 27 to 73
      years). Sites of disease and types of previous therapy varied among the patients.
      Among those with recurrent disease, 30 had locoregional disease, four had
      locoregional disease with distant metastasis, and 17 had distant metastasis only.
      Two patients had distant metastatic disease (MI) at the time of diagnosis. Of the
      53 patients entered, 52 were assessable for disease response and toxic effects.
      Complete response was achieved in nine (17%) of 52 patients and partial response
      in 21 (40%); five (10%) patients had stable disease and 17 (33%) had progressive
      disease. When response rate was analyzed by disease sites, patients with
      locoregional sites showed a 43% major response (complete and partial) rate, and
      those with distant metastatic sites demonstrated an 80% major response rate
      (P=.04). The median duration of disease response in all patients was 4.9 months
      at completion of the study. Among the nine patients with complete response, three
      had progressive disease and the median duration of response was 6.9 months
      (range, 4.9 to 17 months); six were still in remission at the time of this
      writing, with a median duration of response of 12.8 months (range, 6.3 to 18.8+
      months). The median survival time was 8.8 months, and the 1- and 2-year survival
      rates were 40% and 21.9%, respectively. The median follow-up time of the study
      was 11.8 months. The major toxic effects included neutropenia, cumulative
      peripheral neuropathy, and fatigue. Mucositis was rare; grade 3 mucositis
      developed in only one patient. Other side effects included neutropenic fever in
      14 patients, all of whom completely recovered after antibiotic treatment. Grade 3
      orthostatic hypotension and grade 3 peripheral neuropathy developed in one
      patient; supportive care led to gradual recovery. No deaths were caused by toxic
      effects. In conclusion, these preliminary results indicate that the TIP
      chemotherapy regimen produced high rates of major responses in patients with
      recurrent or metastatic head and neck squamous cell carcinoma, and responses were
      durable. The median, 1-year, and 2-year survival times were particularly
      promising. The TIP regimen should be pursued further as an induction regimen for
      locally advanced head and neck cancer.

PMID- 9578062
TI  - Advanced directives: results of a patient survey and commentary from the ethical
      perspective.

PMID- 9578063
TI  - Lessons from 20 years of leading a pediatric nephrology program.
AB  - The patterns of patient referrals, the guidelines for diagnostic procedures and
      treatment, and the academic leadership have continued to change in the last two
      decades. The revolution brought about by molecular biology has dramatically
      changed the pace and direction of medical research during this period. In
      addition, the introduction of managed care competition in the past decade has
      dramatically challenged the practice of medicine. The effects of all these
      changes on nephrology and some lessons learned from developing and leading a
      regional pediatric nephrology program will be discussed. The role of the National
      Institutes of Health in changing research focus will be examined. These
      observations may be useful to those preparing to meet the challenges of clinical
      care and research in this competitive era.

PMID- 9578064
TI  - Measurement of plasma and urinary adrenomedullin in patients with IgA
      nephropathy.
AB  - In this study, we measured plasma and urinary adrenomedullin (AM) concentrations
      in 47 patients with IgA nephropathy. Controls were 39 healthy volunteers. Plasma
      and urinary AM values were measured by specific radioimmunoassay. The plasma AM
      concentrations were higher, and the urinary AM levels were lower in patients with
      IgA nephropathy than in healthy volunteers. Plasma AM concentrations showed a
      positive correlation with serum creatinine and blood urea nitrogen, whereas
      urinary AM levels correlated negatively with serum creatinine and blood urea
      nitrogen. The plasma AM concentrations showed a positive correlation with
      fractional excretions of sodium and potassium. Renal biopsy specimens of patients
      without renal failure were scored for activity (percentage of glomeruli
      demonstrating cellular crescent formation, degree of mesangial proliferation and
      interstitial infiltration; total score = 9). Urinary AM levels were shown to be
      lower in the group with a high activity (score 3-9) as compared with the group
      with a low activity (score 0-2) based on renal biopsy. Thus, urinary levels of AM
      are affected by the degree of the activity in IgA nephropathy, and AM may
      participate in the pathophysiology of IgA nephropathy.

PMID- 9578065
TI  - Histamine and serotonin in uremic pruritus: effect of ondansetron in CAPD
      pruritic patients.
AB  - Pruritus is a common, unpleasant symptom of uremic patients. Serotonin and
      histamine have been reported as possible mediators ofuremic pruritus, and
      ondansetron is a potent and selective inhibitor of 5-HT3 receptors. The aims of
      our study were (1) to evaluate the effect of ondansetron on uremic pruritus in
      continuous ambulatory peritoneal dialysis (CAPD) patients and its safety and (2)
      to investigate the role of histamine and serotonin in uremic pruritus. To study
      the prevalence and pathogenesis of uremic pruritus, CAPD and hemodialysis (HD)
      patients were asked to complete a pruritus questionnaire. The replies were scored
      based on numerical scales, and the results were evaluated by the same
      investigator who did not know the patients. Pruritus was graded, according to the
      total points for each patient, as mild, moderate, or severe. Of 54 patients on
      HD, 29 (53.7%) had pruritus, and of 43 patients on CAPD, pruritus was present in
      21 (48.8%). In HD patients, pruritus was mild in 14 (48.3%), moderate in 12
      (41.4%), and severe in 3 (10.3%) patients; the distribution in CAPD patients was
      9 (42.9%), 10 (47.6%), and 2 (9.5%), respectively. There was no correlation
      between the presence and severity of pruritus and age, sex, primary renal
      disease, duration of dialysis, dialysis solutions used, and hematological and
      biochemical parameters except for serum histamine and serotonin levels and their
      product. Plasma histamine levels in CAPD patients were 13.1 +/- 1.1 ng/ml in
      pruritic and 11.0 +/- 3.9 ng/ml in nonpruritic patients (p = 0.06), serum
      serotonin levels were 115.6 +/- 43.3 ng/ml and 64 +/- 42.3 ng/ml (p < 0.05),
      respectively, and the histamine x serotonin product was 1,461 +/- 576 and 646 +/-
      545 (p < 0.01), respectively. Eleven CAPD patients (6 males, 5 females) with a
      mean age of 66 (range 33-83) years and an average time on CAPD of 18 (range 3-31)
      months with moderate to severe pruritus were treated with ondansetron (4 mg twice
      daily p.o.) for a mean period of 3 (range 1-5) months. All patients responded to
      the treatment. There was a significant reduction of the severity of pruritus from
      the start of treatment, and on the 3rd day the pruritic score (mean value) was 10
      (range 5-19) points, while at time 0 (before treatment) it was 26 (range 19-37)
      points (p < 0.0001). Pruritus disappeared in 7 patients at the end of the 1st
      week and in all patients at the end of the 2nd week of treatment. This effect was
      maintained during the study. Plasma histamine levels decreased significantly
      during the treatment from 12.9 +/- 1.2 to 6.7 +/- 5.9 ng/ml (p < 0.05). Also,
      serum serotonin levels were reduced from 125.1 +/- 47.8 to 59.3 +/- 27.5 ng/ml (p
      < 0.05) at the end of the 1st month of treatment, and the histamine x serotonin
      product showed a more significant reduction: from 1,544 +/- 656 to 454 +/- 436 (p
      < 0.01). Three patients reported an improvement in their nausea and vomiting
      during the treatment. Weekly clinical and laboratory examinations showed no side
      effects, adverse reactions, or other complications. Our data indicate that
      ondansetron is an effective, safe, and well-tolerated drug for the treatment of
      uremic pruritus in CAPD patients and that histamine and serotonin may have a
      crucial role in the appearance or perception of the uremic pruritus.

PMID- 9578066
TI  - Interleukin 12 upregulates the release of vascular permeability factor by
      peripheral blood mononuclear cells from patients with lipoid nephrosis.
AB  - The vascular permeability factor (VPF) is a lymphokine that has been shown to
      play a role in lipoid nephrosis (LN). Prior studies have shown that interleukin
      (IL) 12 promotes T helper type 1 differentiation and enhances production of T
      helper type 1 cytokines such as gamma interferon and IL-2. We, therefore,
      investigated the effects of recombinant human IL-12 on the release of VPF by
      peripheral blood mononuclear cells (PBMC) from LN patients. The VPF activity was
      measured according to the method of Ovary, with minor modifications. The goal of
      the present study was to examine the importance of IL-12 in concanavalin A
      induced VPF release in vitro. The levels of VPF were measured in a group of
      healthy subjects, LN patients with or without the nephrotic syndrome, and
      patients suffering from IgA nephropathy. There was a significantly increased
      concanavalin A induced release of VPF in LN and IgA nephropathy patients with
      nephrotic syndrome as compared with normal controls. Recombinant human IL-12 was
      found to enhance VPF release in a dose-dependent manner. Neutralization of
      endogenously produced IL-12 by anti-IL-12 antibody resulted in a decreased
      release of VPF by LN PBMC. These data indicate that endogenously produced IL-12
      functions as a costimulatory molecule in vitro. Our data show that IL-12 can
      upregulate the release of VPF derived from LN PBMC. Thus IL-12 might be a potent
      adjuvant for inducing VPF. Therefore, IL-12 antagonists may interfere with newly
      initiated and ongoing VPF release associated with nephrotic syndrome.

PMID- 9578067
TI  - Deposition of IgG anti-actin antibodies on kidneys of glomerular nephropathy
      patients with an enhanced glomerular alpha smooth muscle actin expression.
AB  - In this study, we have attempted to evaluate by immunohistochemistry assay the
      glomerular alpha smooth muscle actin (ASMA) expression in 53 kidney biopsy
      specimens obtained from patients with glomerular nephropathy as compared with 16
      histologically normal human kidneys. An enhanced mesangial ASMA expression was
      observed in 26 of 53 specimens of patients with glomerulonephritis. In contrast,
      normal glomeruli showed no ASMA-positive mesangial cells. Furthermore, we have
      analyzed the specificities of antibodies eluted from kidney biopsy specimens from
      patients and controls using an enzyme immunoassay against a panel of self
      antigens composed of actin, myosin, tubulin and DNA. The antibodies eluted from
      exclusively renal biopsy specimens of patients with an enhanced glomerular ASMA
      expression showed high IgG activity restricted to actin. Our results demonstrated
      the presence of IgG anti-actin activity in glomerular nephropathy patients with
      an enhanced mesangial ASMA expression.

PMID- 9578068
TI  - Ultrasound-guided cannulation of the internal jugular vein for dialysis vascular
      access in uremic patients.
AB  - BACKGROUND: A reliable temporary vascular access is always required for
      hemodialysis when a permanent vascular access is not available. However,
      techniques for creating temporary vascular accesses remain imperfect. This study
      utilized the 'SiteRite' ultrasound device to improve both success and
      complication rates of jugular venous cannulation for temporary access. METHODS:
      This prospective, comparative study recruited 104 uremic patients receiving
      ultrasound-guided and 86 patients undergoing landmark-guided percutaneous
      internal jugular venous cannulation of dual-lumen dialysis catheters. Success
      rate, number of puncture attempts, access time, and the complication rate of the
      ultrasound technique, in comparison with the landmark-guided technique, were
      studied. RESULTS: The ultrasound-guided cannulation was superior to the external
      landmark-guided cannulation in overall success rate (99.0 vs. 86.0%, p < 0.01),
      success rate of the first puncture attempt (80.8 vs. 34.9%, p < 0.01), average
      puncture (access) times (15.8 vs. 43.7 s, p < 0.01), puncture trials (1.39 vs.
      2.58, p < 0.01), and traumatic complication rate (1.9 vs. 1 1.6%, p = 0.015). The
      incidence of infective complications for the ultrasound group was not different
      from that of the landmark-guided groups (2.9 vs. 2.3%, p = 0.589). CONCLUSION:
      The ultrasound-guided technique offers both safety and convenience in inserting
      jugular venous dialysis catheters. It represents a valuable technique in creating
      temporary dialysis hemoaccesses.

PMID- 9578069
TI  - Effect of hemodialysis on the dispersion of the QTc interval.
AB  - The QTc dispersion reflects the underlying regional heterogeneity of the recovery
      of the ventricular excitability, thereby it is considered as a novel marker of
      risk of ventricular arrhythmias. Because a higher incidence of ventricular
      arrhythmias is described during and after hemodialysis, the aim of this study has
      been to evaluate the QTc dispersion before and after uncomplicated hemodialysis
      session. Twenty chronic uremics without heart failure, ischemic heart disease or
      dialysis hypotension were selected. The QTc dispersion was determined as the
      difference between the longer and the shorter QTc interval measured on a 12-lead
      electrocardiogram. Following the hemodialysis session, the QTc dispersion
      increased from 30 +/- 9 to 54 +/- 17 ms (p < 0.001) associated with the expected
      reduction of potassium and magnesium and with the increase of extracellular
      calcium concentration. However, no correlation has been observed between the QTc
      dispersion increase and the degree of the intradialytic changes of plasma
      electrolytes, blood pressure or body weight. In summary, the hemodialysis
      treatment per se does induce an increase of the QTc dispersion, likely due to the
      rapid changes of electrolyte plasma concentrations. This can potentially
      contribute to the arrhythmogenic effect of the hemodialysis procedure, reflecting
      an enhanced regional heterogeneity of ventricular repolarization. The clinical
      importance of the increase of QTc dispersion as risk factor of ventricular
      arrhythmias, particularly in hemodialyzed patients suffering from ischemic or
      hypertrophic heart diseases, should be the matter of further investigations.

PMID- 9578070
TI  - Effects of chitosan-coated dialdehyde cellulose, a newly developed oral
      adsorbent, on glomerulonephritis induced by anti-Thy-1 antibody in rats.
AB  - The effects of chitosan-coated dialdehyde cellulose (chitosan DAC), a newly
      developed oral adsorbent for urea and ammonia, were examined in a
      glomerulonephritis model in rats. Mesangial proliferative glomerulonephritis
      accompanied with proteinuria was induced by an intravenous injection of anti-rat
      Thy-1.1 monoclonal antibody (OX-7). The proliferation of mesangial cells and an
      accumulation of extracellular matrix components such as type I collagen and
      fibronectin were observed in the glomeruli 9 days after OX-7 injection; these
      were improved in rats fed a diet containing chitosan DAC (10% content) for 9 days
      compared with those in rats fed a normal diet. Chitosan DAC treatment decreased
      the elevated urinary protein and blood urea nitrogen at days 8-9 to the normal
      levels; the increased fecal excretion of nitrogen might participate in this
      phenomenon. In addition, chitosan DAC treatment showed an increase in fecal water
      content associated with a decrease in urinary volume. These therapeutic effects
      may be due to the reduction of proteinic factor expression and the compensational
      function of chitosan DAC for kidney. These results suggest that chitosan DAC
      treatment may be useful for ameliorating mesangial proliferative
      glomerulonephritis.

PMID- 9578071
TI  - Experimental focal segmental glomerulosclerosis in mice.
AB  - Although a lot of animal models of proteinuria have been established, proposals
      for the mechanisms of proteinuria are still controversial. In this work, during
      an 18-day trial, mice injected with a single dose of adriamycin (AD) rapidly
      showed combined glomerular albuminuria and immunoglobulinuria, progressively
      elevated levels of nitrite/nitrate in urine, hypercholesterolemia, abnormal renal
      function, segmentally or globally glomerular hyalinosis/sclerosis associated with
      tubular atrophy, enhanced glomerular deposition of immunoglobulins and
      fibrinogen, augmented expression of matrix components in the whole glomerular
      tuft, and loss of glomerular negative charge property. These laboratory and
      pathological features are comparatively similar to those of human focal segmental
      glomerulosclerosis in the advanced state. Juxtamedullary glomeruli appear to be
      more susceptible to the AD-related nephrotoxicity than those in the superficial
      renal cortex. A change in size-dependent glomerular permselectivity may precede a
      charge-dependent defect in glomeruli in this mouse model of proteinuria. Data in
      this study confirm the hypothesis of glomerular hyperfiltration involved in the
      pathogenesis of this chronic glomerulopathy associated with proteinuria in mice.
      In addition, nitric oxide may play a crucial role in the progression of the
      chronic glomerulopathy model.

PMID- 9578072
TI  - Comparative nephritogenicity of two monoclonal antibodies that recognize
      different epitopes of rat Thy-1.1 molecule.
AB  - The pathophysiological role of the Thy-1.1 molecule expressed on rat mesangial
      cells with regard to mesangial cell dysfunction and injury remains unknown. The
      mechanism of Thy-1.1-associated injury has now been investigated with two
      monoclonal antibodies, 1-22-3 and OX7, that recognize different epitopes of Thy
      1.1. Mesangiolysis and mesangial cell proliferation were more marked in rats
      injected with 1-22-3 than in those treated with OX7. Immunostaining for rat
      complement component C3 and also C9 was similar in the kidneys of rats 1 h after
      injection of either antibody. Alpha smooth muscle actin was first detected 3 days
      after injection of 1-22-3 and peaked on day 5; type I collagen staining showed a
      mesangial pattern on days 5 and 10. The staining for alpha smooth muscle actin
      and type I collagen was less intense in OX7-treated rats than in the 1-22-3
      injected rats. The amounts of mRNAs encoding collagen types I and III peaked 5
      days after injection of 1-22-3 and 10 days after injection of OX7. Rats injected
      with 1-22-3 developed proteinuria that was already marked on day 1 and peaked at
      150 mg/day on day 3, whereas OX7 induced a low grade of proteinuria with large
      interindividual variability on day 3. Immunostaining for rat C3 in the normal rat
      kidneys, incubated in vitro with 1-22-3 or OX7 followed by incubation with normal
      rat fresh serum as a complement source, as well as the levels of serum complement
      activity, CH50, 30 min after injection of 1-22-3 or OX7 were similar, suggesting
      that the difference in the nephritogenicity of these two antibodies is not
      attributable to a difference in their complement-fixing activities, but rather
      may result from the difference in epitope specificities. The epitope recognized
      by 1-22-3 thus appears to be important in the initiation and progression of
      antibody-induced nephritis.

PMID- 9578073
TI  - Anti-idiotype antibody directly interferes with glomerular IgA immune complex
      deposition.
AB  - Data from both animal and clinical studies suggest that anti-idiotype antibodies
      deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis.
      This study was conducted to examine the role of a hybridoma-AB1-2-derived IgG
      anti-T15 idiotype (IgG anti-T15) in the immunopathogenesis of a short-term
      experimental IgA nephropathy. BALB/c mice (12/group) were administered
      intravenously with: (1) an equal mass (1 mg) of T15-hybridoma-derived IgA
      antiphosphorylcholine (PC) and PC-conjugated bovine serum albumin (BSA-PC)
      antigen; (2) 1 mg of IgA anti-PC, 1 mg of BSA-PC antigen, and 3 mg of IgG anti
      T15, or (3) 1 mg of BSA-PC antigen alone. The mice were sacrificed 6 h after the
      injection. A 6-hour clearance study was performed. The initial phase of
      elimination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15
      or those receiving the antigen alone was significantly faster than that in those
      receiving IgA anti-PC/BSA-PC (p < 0.001). There was no significant difference in
      the elimination rate of BSA-PC antigen between mice receiving IgA anti-PC/BSA
      PC/IgG anti-T15 and those receiving BSA-PC antigen alone. The late phases of
      elimination of the BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti
      T15 showed somewhat similar to those of BSA-PC antigen in mice receiving IgA anti
      PC/BSA-PC. Moreover, mice injected with IgA anti-PC/BSA-PC/IgG anti-T15 showed a
      significantly less glomerular BSA-PC antigen deposition than those injected with
      IgA anti-PC/BSA-PC (positive control), as demonstrated by light microscopy,
      autoradiography, and immunohistochemistry (each p < 0.001). It is inferred that
      the injected IgG anti-T15 could react with the IgA anti-PC in vivo, directly
      interfering with immune complex formation by the IgA anti-PC and BSA-PC antigen,
      thereby resulting in diminished glomerular deposition of the BSA-PC antigen.
      These findings suggest that an anti-idiotype antibody may be protective in the
      immunopathogenesis of IgA nephropathy, because of its inhibitory effect on
      glomerular trapping of an antigen.

PMID- 9578074
TI  - Effect of protamine on cation-selective permeability in hamster medullary thick
      ascending limb of Henle's loop.
AB  - To estimate the contribution of the paracellular shunt pathway to cation
      selective permeability in the hamster medullary thick ascending limb of Henle's
      loop, we observed the effect of protamine, a selective blocker of paracellular
      conductance, on salt-diffusion voltage (dVT) in the isolated nephron segment
      perfused in vitro. When 300 microg/ml protamine was added to the lumen, the lumen
      positive dVT generated upon reduction of the lumen NaCl concentration was
      decreased from 5.1 +/- 0.9 to 0.8 +/- 0.8 mV and the calculated Na+/Cl-
      permeability ratio was decreased from 1.40 +/- 0.14 to 0.86 +/- 0.08. Although
      the effect of protamine persisted after removal of the agent from the lumen,
      addition of 30 U/ml heparin, which neutralizes protamine, returned the dVT toward
      the control level. This effect was almost the same when the orientation of the
      imposed NaCl gradient was reversed. Protamine exhibited a similar effect on dVT
      in the presence of ouabain added to the bath. Protamine was without effect from
      the bath. Protamine did not affect the basel VT perfused with the control
      solution. Increased VT by decreasing perfusion pressure was inhibited by adding
      protamine from the lumen. These observations suggest that the paracellular
      pathway contributes to the cation selectivity of the medullary thick ascending
      limb. The cation selectivity of the paracellular shunt pathway may mainly account
      for the changes in VT which are either dependent on the luminal flow rate or
      transmural NaCl concentration gradient, while it may not contribute to the basal
      level of VT.

PMID- 9578075
TI  - Nephrotic syndrome, hyperreninemia and multiple transplant renal arterial
      stenoses in a patient with diabetes.
AB  - Nine months after cadaveric renal transplantation the nephrotic syndrome
      developed in a patient with insulin-dependent diabetes. Renal biopsy ruled out
      tissue lesions induced by cyclosporine, chronic rejection, recurrence of diabetic
      kidney disease and de novo glomerulopathies. Captopril-enhanced nephrography and
      a high plasma renin response suggested renal artery disease. Angiography revealed
      five intrarenal arterial stenoses. Four were successfully dilated with a prompt
      diuretic response and diminished proteinuria. Late angiography showed a moderate
      restenosis in two of the dilated arteries. Due to persistent proteinuria,
      elevated blood pressure and higher serum creatinine levels than at nadir after
      transplantation low-dose ACE inhibitor therapy was started. This normalized
      proteinuria, blood pressure and serum creatinine levels. This beneficial response
      to combined renal artery balloon angioplasty and medical treatment has been
      sustained for 2.5 years.

PMID- 9578076
TI  - Variable presentation of primary hyperoxaluria type 1 in 2 patients homozygous
      for a novel combined deletion and insertion mutation in exon 8 of the AGXT gene.
AB  - Two unrelated patients of Pakistani origin presented with primary hyperoxaluria
      type 1 (PH1) at 4 months and 3 years of age, respectively. While the younger
      patient failed to thrive and suffered from early renal failure, the older one
      showed a relatively benign history with urolithiasis as the main feature of the
      disease. In both patients the diagnosis was confirmed by assessment of
      alanine:glyoxylate aminotransferase catalytic and immunoreactivity in liver
      biopsy specimens. The underlying genetic defect was found to be a combined
      deletion and insertion in exon 8 which alters the reading frame of the protein.
      The nucleotide change introduces a Stu1 restriction site which facilitated typing
      of additional family members. Both patients and a further affected brother were
      homozygous for this mutation, while their parents were heterozygous for it. This
      mutation is the first deletion/insertion identified in PH1. Although rare in our
      PH1 patient cohort (2.5% of alleles), the finding of 2 homozygous apparently
      unrelated individuals of the same ethnic origin suggests that it may prove
      worthwhile to screen other Asian patients for this mutation. These PH1 cases
      present further evidence that factors other than genotype contribute
      significantly to the clinical presentation and severity of PH1.

PMID- 9578077
TI  - Can acipimox reduce serum lipoprotein(a) levels in hemodialyzed patients?

PMID- 9578078
TI  - Increased soluble CD4 and CD8 in chronic renal failure.

PMID- 9578079
TI  - Hodgkin's disease-like lymphoproliferative disorders in patients with different
      underlying immunodeficiency states.
AB  - Epstein-Barr virus (EBV)-associated lymphoproliferative diseases are a frequent
      occurrence in immunodeficient patients. Most commonly seen are polymorphic B-cell
      lymphoproliferative disorders and malignant B-cell lymphomas. Classical Hodgkin's
      disease (HD), however, is rare in these patients. In the present study, we
      attempted to characterize cases resembling HD in patients with a variety of
      underlying immunodeficiency states using clinical aspects, immunohistochemistry,
      in situ hybridization, and polymerase chain reaction. All of the six cases that
      we investigated presented clinically with B symptoms and a short, devastating
      course. Histologically, they showed a lymphocytic depletion and multiple cells
      that resembled HD and Reed-Sternberg cells. Many of those were atypical blast
      cells that stained positively for B-cell surface antigens, such as CD20 and
      CD79a, whereas others were of the typical HD and Reed-Sternberg phenotype.
      Another frequent finding, especially in the extranodal sites, was a perivascular
      arrangement of large blast cells intermingled with small lymphoid cells. All of
      the cases were EBV-associated (proved latent membrane protein-1
      immunohistochemical analysis, EBV-encoded RNA in situ hybridization, and
      polymerase chain reaction for subtypes A and B), with a frequent coinfection of
      type A and B. This was in contrast to ordinary HD, which is characterized by
      single infection of only one strain, i.e., the subtype A in Western countries.
      Three cases showed clonal B-cell populations, at least at terminal stages of the
      disease. We describe a lymphoproliferative disorder in immunodeficient patients
      with features of HD that, in some respects, resembles an EBV-driven
      lymphoproliferative disorder seen in cases of fatal infectious mononucleosis. We
      conclude that clinical and pathologic features of these disorders might cause
      some problems for histologic differential diagnosis and might represent a
      separate entity of their own in immunodeficient patients.

PMID- 9578080
TI  - Perforin and granzyme expression in cytotoxic T-cell lymphomas.
AB  - We studied the morphologic and immunohistochemical features of 10 peripheral T
      cell lymphomas of a cytotoxic phenotype (CD3+/CD4-/CD8+), encountered among 98
      peripheral T-cell lymphomas (PTCLs). Nine tumors were positive for both cytotoxic
      molecules, namely perforin (Pf) and granzyme B (GrB), and strong positivity was
      seen in the majority of the malignant cells. We also studied the expression of
      these molecules in 92 other cases of T-cell and natural killer (NK) cell
      neoplasms; 18 anaplastic large cell lymphomas (ALCLs); 63 CD4+ PTCLs; 10 CD56+
      nasal lymphomas; and 1 NK-cell leukemia. Most of the CD4+ PTCLs (62 of 63) were
      negative for GrB, but all of the nasal lymphomas and the NK cell leukemia were
      positive for both Pf and GrB. Variable expression was seen among the 18 ALCLs.
      Within the 10 CD8+ PTCLs, 4 involved the skin, 3 of which were diagnosed as
      primary cutaneous lymphomas. Five patients died within 1 year of diagnosis.
      According to the Revised European-American Classification of Lymphoid Neoplasms,
      seven cases were categorized as "PTCL, unspecified," and three as
      "angioimmunoblastic T-cell lymphoma," "adult T-cell lymphoma/leukemia," or "small
      cell lymphoma," respectively. Three cases had characteristic morphologic features
      consisting of large lymphomatous cells with massive necrosis and nuclear
      fragmentation. Epstein-Barr virus mRNA was detected by in situ hybridization in
      three cases. Although the degree of apoptosis varied, apoptotic cells were
      detected in all cases by terminal deoxynucleotidyl transferase-mediated
      deoxyuridine 5-triphosphate-biotin nick end labeling. We conclude that CD8+ PTCLs
      are relatively rare, often involve extranodal sites, have an aggressive clinical
      course, and are often associated with Epstein-Barr virus. Compared with ALCLs,
      which have recently been considered as neoplasms of cytotoxic T-cells, we think
      that CD8+ PTCLs are more lineage-specific neoplasms of mature, cytotoxic, T
      lymphocytes.

PMID- 9578081
TI  - Expression of p27kip1 in prostatic adenocarcinoma.
AB  - p27kip1 (p27) protein is an inhibitor of cyclin and cyclin-dependent kinase
      complexes and prevents progression of cells from G1 to the S phase of the cell
      cycle. p27 might have tumor suppressor activity, and decreased p27 expression is
      associated with aggressive tumor behavior in several human malignancies. The
      object of this study was to evaluate p27 expression in prostatic adenocarcinoma
      treated by radical prostatectomy and to assess its association with numerous
      morphologic and clinical features. One hundred thirty-eight prostatic
      adenocarcinomas were evaluated for p27 expression by quantifying nuclear
      immunohistochemical staining. p27 expression was tested for association with
      patient age, family history of prostate cancer, preoperative serum prostate
      specific antigen level, Gleason score, extraprostatic extension, seminal vesicle
      involvement, lymph node metastases, tumor-node-metastasis stage, DNA ploidy by
      flow cytometric analysis, and subclinical biochemical failure. p27 expression was
      analyzed as a continuous variable, and we also classified the tumors as low
      expressors (< 50% of cells p27 positive) or high expressors (> 50% of cells p27
      positive) for comparison. Patients with adenocarcinomas that exhibited low p27
      expression had higher mean Gleason scores than did high expressors (7 vs. 6.2,
      respectively; P = .002). Low p27 expression correlated with positive surgical
      margins (P = .05), seminal vesicle involvement (P = .007), lymph node metastasis
      (P = .03), and aneuploid cancers (P = .003), but it did not correlate with
      subclinical biochemical failure. p27 expression correlated with a number of
      prognostic morphologic features in prostatic adenocarcinoma, and the evaluation
      of p27 expression might provide additional prognostic information.

PMID- 9578082
TI  - Vascularity in human adrenal cortex.
AB  - It has long been postulated that angiogenesis plays important roles in tumor cell
      proliferation and hormonal secretion of endocrine tumors, including
      adrenocortical neoplasms. Detailed examination of vascularity, however, has not
      been reported in adrenocortical tumors. In this study, we quantitatively examined
      vascularity in normal adrenal, adrenocortical adenoma, and carcinoma using an
      image analysis system to evaluate vascularity or angiogenesis in these lesions.
      Vascular density (VD: vessel number/mm2), endothelial area of each vessel (EA:
      microm2/vessel) and vascular area (VA: the percentage of EA per field) were
      examined using immunohistochemical analysis of CD34 and the CAS 200 image
      analysis system. EA and VA of adrenocortical carcinomas (EA, 113.4 +/- 33.1; VA,
      6.34 +/- 2.03) were significantly higher than those of adenoma (EA, 66.1 +/-
      43.0; VA, 3.11 +/- 1.56) and normal adrenal tissue (EA, 65.4 +/- 26.0; VA, 4.26
      +/- 1.19). There were no significant differences in VD among normal cases (702.2
      +/- 173.2), adenomas (488.9 +/- 153.2), and carcinomas (573.2 +/- 185.2). These
      results suggest that adrenocortical carcinoma might be associated with increased
      endothelial cell proliferation but not with an increased number of intratumoral
      microvessels. There were no significant differences in these parameters of
      vascularity examined in the zona glomerulosa, zona fasciculata, and zona
      reticularis of aldosteronomas, Cushing's adenomas, and nonfunctioning hormonally
      inactive adenomas nor between specimens from patients who died of the disease and
      those from patients who did not.

PMID- 9578083
TI  - Neuropathologic applications of immunohistochemical fiber typing in the non
      neoplastic muscle biopsy.
AB  - The determination of fiber types is routinely accomplished in skeletal muscle
      biopsy specimens by enzymatic histochemical analysis, which detects adenosine
      triphosphatase (ATPase) activity on cryostat sections. This study assesses
      postmortem antigen degradation, the effects of fixation and processing, and the
      neuropathologic applications of MY-32, a monoclonal antibody to fast twitch
      skeletal myosin. Formalin-fixed, paraffin-embedded sections of skeletal muscle
      biopsy specimens obtained from the quadriceps femoris were immunoreacted with
      this antibody. Cryostat sections of the same muscle biopsy specimens were
      examined after brief fixation in either acetone or formalin. Parallel cryostat
      sections of frozen muscle were also assessed with ATPase preparations at pH 9.4
      and 4.3. To evaluate the effect of postmortem interval and autolysis on antigen
      degradation, skeletal muscle samples obtained at 12 hours postmortem were
      immunoreacted after 12, 24, or 36 additional hours. These specimens were examined
      as immunoreacted cryostat sections and compared with parallel sections reacted
      for ATPase at pH 9.4 and 4.3. Representative sections from each time point were
      also fixed in formalin, routinely processed, paraffin embedded, and
      immunoreacted. Selected muscle biopsy specimens with a range of neuropathologic
      diagnoses, including fiber type grouping, Type II atrophy, and congenital fiber
      type disproportion, were also assessed for immunoreactivity. Our results indicate
      that the MY-32 monoclonal antibody specifically reacts with Type II (fast twitch)
      fibers. Immunoreactivity is most intense in cryostat sections immersion fixed in
      acetone, but moderately intense, specific immunoreactivity can be clearly
      identified in formalin-fixed (frozen or paraffin-embedded) tissue obtained even
      48 hours after death. Application of this nonenzymatic method for fiber type
      determinations in the neuropathologic evaluation of skeletal muscle biopsies is
      presented.

PMID- 9578084
TI  - Image analysis of proliferating cell nuclear antigen expression and
      immunohistochemical profiles in renal cell carcinoma associated with acquired
      cystic kidney disease: comparison with classic renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) arising in acquired cystic kidney disease (ACKD) is
      considered to be a tumor of low malignant potential, compared with classic RCC.
      The aim of the present study was to identify any significant differences in the
      antigenic profiles or tumor cell proliferative activity of ACKD-associated RCC
      and classic RCC that might be responsible for differences in their biologic
      behavior. We studied the immunohistochemical profiles and proliferative activity
      of 12 classic RCCs and 5 ACKD-associated RCCs with markers of proximal tubules
      (Leu M1, alpha-1 antitrypsin, CAM 5.2), markers of distal tubules (Arachis
      hypogaea lectin, AE1/AE3, epithelial membrane antigen [EMAJ, CAM 5.2), vimentin,
      and proliferating cell nuclear antigen (PCNA). We performed proliferation
      analysis with the CAS 200 image analysis system. For each case, 8 to 20 fields of
      tumor tissue in the areas of maximal PCNA staining were quantitated, and the
      percentage of PCNA-positive nuclear area for each individual tumor was
      calculated. All of the five ACKD-associated RCCs expressed AE1/AE3, EMA, and CAM
      5.2 in more than 50% of the tumor cells. Arachis hypogaea lectin was
      significantly expressed in three of the five ACKD-associated RCCs. Leu M1 and
      alpha-1 antitrypsin reacted with fewer than 10% of the tumor cells in all of the
      five ACKD-associated RCCs. In contrast, the 12 classic RCCs showed expression of
      CAM 5.2 in 11 cases, alpha-1 antitrypsin in 10 cases, Leu M1 in 9, EMA in 8, and
      AE1/AE3 in 3 cases in more than 50% of the tumor cells and a totally negative
      reaction with Arachis hypogaea lectin in 8 cases, EMA in 4, AE1/AE3 in 4, and
      vimentin in 5 cases. Although coexpression of proximal and distal tubule markers
      was seen in some cases of RCC in either category, there was uniform and strong
      staining for distal tubule markers in ACKD-associated RCC and for proximal tubule
      markers in classic RCC. The mean percentage of PCNA-positive nuclear area for the
      ACKD-associated RCCs (2.41%) was significantly (P < .05) less than that of the
      classic RCCs (21.42%). The differences in expression of proximal and distal
      tubule markers and proliferative activity might be responsible for the
      differences in the biologic behavior of ACKD-associated RCC and classic RCC.

PMID- 9578085
TI  - Pulmonary lymphomatoid granulomatosis in acquired immunodeficiency syndrome:
      lesions with Epstein-Barr virus infection.
AB  - We report the clinicopathologic characteristics of pulmonary lymphomatoid
      granulomatosis (LYG) in 11 patients (identified from a series of 330 consecutive
      patients who underwent autopsy between 1984 and 1995 at the University of Texas
      Medical Branch at Galveston, Texas) with a diagnosis of acquired immunodeficiency
      syndrome (AIDS). We used immunohistochemical stains, RNA in situ hybridization
      (ISH), and gene rearrangement studies to identify the immunophenotype and the
      presence or absence of Epstein-Barr virus (EBV) infection. All of the patients
      were men ranging in age from 27 to 65 years (mean age, 38.6 yr). Autopsy lungs of
      21 age-matched controls were examined for EBV using ISH; these included 9
      patients with AIDS who did not have pulmonary lesions and 12 HIV-negative
      individuals who died accidentally (mean age, 38.6 yr). All of the 11 pulmonary
      lesions showed the gross and microscopic characteristics of LYG, with zonal
      necrosis and prominent angioinvasion. The tumor nodules consisted of a mixture of
      atypical large lymphocytes, with vesicular nuclei and prominent nucleoli and with
      a background of small and intermediate-size lymphocytes, histiocytes, and plasma
      cells. The large lymphocytes were CD20 positive, consistent with a B-cell
      phenotype. Ten of the 11 cases demonstrated EBV1-encoded RNA and CD20 positivity
      in the large, atypical lymphocytes by double labeling. One patient showed EBV
      positivity in CD20-negative, CD45RO-positive large cells, but these cells were
      CD3 negative and showed a monoclonal heavy chain gene rearrangement by polymerase
      chain reaction, indicating that these were of B-cell origin. Aberrant CD43
      coexpression was identified in four cases. EBV latent membrane protein was
      demonstrated in 9 of 11 cases by immunohistochemical stains. The lungs of all of
      the 21 control patients were negative for EBV by ISH. We conclude that, in our
      series, AIDS-associated LYG is a B-cell neoplasm and that it has a strong
      association with EBV infection.

PMID- 9578086
TI  - Use of antibodies against estrogen and progesterone receptors to identify
      metastatic breast and ovarian carcinomas by conventional immunohistochemical and
      tyramide signal amplification methods.
AB  - The immunohistochemical detection of estrogen receptors (ERs) and progesterone
      receptors (PRs) is useful for the differentiation of cytostatically treatable
      breast and ovarian carcinomas from other metastatic adenocarcinomas of unknown
      primary sites. We retrospectively studied metastases of 68 breast, 24 ovarian, 15
      bronchogenic, 35 gastric, 22 pancreatic, 23 colonic, 27 renal cell, and 26
      primary bronchogenic carcinomas by using a panel of 3 antibodies against ERs and
      4 antibodies against PRs and applying both a conventional immunohistochemical
      detection method and the highly sensitive tyramide signal amplification (TSA)
      technique. Antibody 6F11 against ERs was slightly more sensitive than clone 1D5
      with both detection methods, staining 5% more breast carcinomas and 4% more
      ovarian carcinomas with TSA, compared with conventional immunohistochemical
      analysis. Furthermore, clone 6F11 detected ERs in 4 of 26 primary bronchogenic
      carcinomas and 1 of 35 metastases of gastric carcinomas with conventional
      immunohistochemical techniques; an additional 9 primary and 6 metastatic
      bronchogenic carcinomas and 2 metastatic gastric carcinomas were positive with
      TSA. The resulting specificities for breast and ovarian carcinomas versus all
      other carcinomas were 0.97 with conventional immunohistochemical techniques and
      0.85 with TSA. Antibody 1A6 against PRs was slightly more sensitive but least
      specific for breast and ovarian carcinomas (specificity was 0.96 with
      conventional immunohistochemical methods and 0.91 with TSA), compared with
      antibody hPRa3 and a polyclonal antibody (specificity was 1.00 with both
      detection methods). Antibodies TE111 against ERs and 10A9 against PRs were
      significantly less sensitive than the other antibodies. We conclude that TSA
      cannot be recommended for the detection of ERs and PRs to differentiate breast
      and ovarian carcinomas from other metastatic adenocarcinomas of unknown primary
      sites.

PMID- 9578087
TI  - Inflammatory myofibroblastic tumor: cytogenetic evidence supporting clonal
      origin.
AB  - The inflammatory myofibroblastic tumor (IMT) is a distinctive but controversial
      lesion, usually occurring during childhood, composed of fascicles of bland
      myofibroblastic cells admixed with a prominent inflammatory infiltrate consisting
      of lymphocytes, plasma cells, and eosinophils. Often affecting the lung and
      associated with constitutional symptoms, this lesion has been variously termed
      plasma cell granuloma, inflammatory pseudotumor, inflammatory myofibrohistiocytic
      proliferation, and inflammatory fibrosarcoma to reflect divergent views
      concerning its pathogenesis and level of malignancy. Cytogenetic analysis of an
      intra-abdominal myxoid hamartoma, a probable variant of this lesion, and a
      pulmonary IMT demonstrated clonal chromosomal abnormalities, lending support to
      the view that the IMT might be a neoplasm. There have been few cases studied to
      date, however, and the extent of cytogenetic anomalies in IMTs is not known.
      Karyotype analyses were performed on IMTs showing typical histologic features
      from three children. In addition, one case was studied by fluorescence in situ
      hybridization. Seventeen of 20 metaphase cells examined from a pulmonary IMT in a
      5.5-year-old girl had an abnormal 47,XX+r(ring) karyotype. Fluorescence in situ
      hybridization studies demonstrated that the ring chromosome contained sequences
      of chromosome 8. Of 40 metaphase cells studied from a mesenteric IMT in an 8
      month-old boy, 12 showed clonal aberrations, characterized as
      43,XY,add(1)(p36),add(2)(p24),-6,der(14,22)(q10;q10),-19. Each of 20 metaphase
      cells examined from a retroperitoneal IMT in a 14-year-old girl contained complex
      clonal and nonclonal aberrations, characterized as 46-47,X,
      X,add(2)(p22),add(2)(q13),+add(2)(q13),+5,-6,+i(7)(p10),add(8)(
      p11.2),+del(9)(p13),add(11)(p11.2)add(11)(q25),-13,-16,-18,add(19)(q13.1
      ),add(19)(q13.1),+20,-21,-22,+mar1,+1-2mars. The presence of clonal chromosomal
      aberrations in all of the three tumors indicates that the IMT is a neoplastic
      proliferation.

PMID- 9578088
TI  - Fas ligand expression in nodal non-Hodgkin's lymphoma.
AB  - Fas (Apo-1/CD95) ligand (FasL) is a cytotoxic molecule used by T lymphocytes and
      natural killer cells for target-cell killing and by nonmalignant and malignant
      cells in the suppression of immune responses. In this study, FasL expression in B
      and T-cell non-Hodgkin's lymphomas was investigated by paraffin
      immunohistochemical analysis. FasL expression was found to be weak in
      nonaggressive lymphomas (chronic lymphocytic leukemia/small lymphocytic lymphoma,
      lymphoplasmacytoid lymphoma, Grade 1 follicular center cell lymphoma) and mantle
      cell lymphoma but strong in aggressive B-cell lymphomas (diffuse large B-cell
      lymphoma, Burkitt's-lymphoma). Precursor B-lymphoblastic lymphomas were more
      heterogeneous, with expression varying from weak to strong. In T-cell lymphomas
      (anaplastic large-cell lymphoma; peripheral T-cell lymphoma, unspecified), strong
      FasL expression was observed. Apparently, FasL expression is not limited to
      neoplasms derived from T cells or natural killer cells, and it might play a
      supporting role in the progression of non-Hodgkin's lymphomas.

PMID- 9578089
TI  - Low p53 and high bcl-2 expression in Reed-Sternberg cells predicts poor clinical
      outcome for Hodgkin's disease: involvement of apoptosis resistance?
AB  - A high number of activated cytotoxic T lymphocytes (CTL) in Hodgkin's disease
      (HD) biopsy specimens is related to an unfavorable clinical outcome, suggesting
      that resistance of the Hodgkin and Reed-Sternberg (H-RS) cells to CTL-mediated
      killing is an important pathogenic factor in HD. bcl-2 and defective p53 are
      known to inhibit apoptosis induced either by CTLs or by therapy. The purpose of
      this study was to use immunohistochemical techniques to analyze whether
      differences in expression of these proteins in H-RS cells in primary biopsy
      specimens from 78 patients with HD were related to clinical outcome and to assess
      the number of CTLs in those cells. Cases with H-RS cells mostly staining positive
      for bcl-2 but negative for p53 had a poor prognosis (55% 5-yr survival). In the
      group of patients whose H-RS cells had low positivity for both p53 and bcl-2, the
      5-year survival was 90%. p53 expression in a high percentage of H-RS cells was
      invariably related to a 100% 5-year survival, irrespective of bcl-2 expression.
      Biopsy specimens from patients with a fatal clinical outcome, in which few H-RS
      cells expressed p53 and many H-RS cells expressed bcl-2, contained relatively
      many activated CTLs. These data demonstrate that the combination of expression of
      the apoptosis-regulating proteins p53 and bcl-2 in the H-RS cells can be used as
      a prognostic marker for HD, and they indicate that resistance to apoptosis of H
      RS cells is an important pathogenic mechanism. Our data also support the
      hypothesis that in patients with a poor prognosis, apoptosis-resistant H-RS cells
      might be selected for by the presence of many activated CTLs.

PMID- 9578090
TI  - Inflammatory myxohyaline tumor of distal extremities with virocyte or Reed
      Sternberg-like cells: a distinctive lesion with features simulating inflammatory
      conditions, Hodgkin's disease, and various sarcomas.
AB  - We report 51 cases of a previously undescribed tumor of the distal extremities
      that is often mistaken for an inflammatory or infectious process, Hodgkin's
      disease, or various sarcomas. These lesions developed in patients of all ages
      (range, 4-81 yr; median, 40 yr) and affected the sexes nearly equally (27 men, 24
      women). They presented as a painless mass of the fingers (14 cases), hand (11
      cases), wrist or arm (10 cases), toe or foot (8 cases), or lower leg (5 cases),
      usually within the subcutaneous tissues. Grossly, they were infiltrative,
      multinodular masses characterized by a dense chronic inflammatory infiltrate that
      merged with a stroma, which varied from densely hyaline to focally myxoid and
      contained sheets of short spindled to rounded epithelioid cells. Focally, the
      epithelioid cells were extremely large with bizarre, vesicular nuclei and
      macronucleoli resembling Reed-Sternberg cells or virocytes. Despite the level of
      atypia, mitotic activity was low. The tumor cells consistently expressed vimentin
      but lacked a variety of other mesenchymal, epithelial markers, e.g., S100
      protein, desmin, actin, neuron-specific endolase, epithelial membrane antigen,
      HMB-45, CD34) and leukocyte markers (CD15, CD30, CD45). Keratin was noted focally
      and weakly in four cases and CD68 focally in six cases, the latter suggesting
      that the cells had acquired phagocytic properties. Immunostains for
      cytomegalovirus were negative. Polymerase chain reaction for Epstein-Barr virus
      showed amplification levels consistent with latent infection in 4 of 10 cases,
      but no cases showed levels consistent with active infection. All of the bacterial
      and viral cultures were negative. Follow-up information was available in 27
      cases. Recurrences developed in six patients (interval, 15 mo-10 yr), but there
      were no metastases or tumor-related deaths. In one patient, progressive proximal
      extension up the arm was noted. Although the most common submitting diagnosis was
      that of an inflammatory or infectious process, the negative studies for
      infectious agents, clinical behavior with local recurrences, immunophenotypic
      profile, and cytologic atypia support the idea that these are unusual mesenchymal
      neoplasms with at least the potential for local recurrence. It remains to be
      investigated whether with time these lesions will prove to have metastatic
      potential.

PMID- 9578091
TI  - GLUT1 glucose transporter: a highly sensitive marker of malignancy in body cavity
      effusions.
AB  - Malignant cells exhibit increased rates of glycolysis and glucose uptake, and
      several types of cancer have been reported to overexpress the GLUT1 glucose
      transporter. The diagnosis of malignancy in body cavity effusions remains a
      dilemma in certain cases, despite recent progress in diagnostic
      immunocytochemistry. We used immunostaining to detect the facilitative glucose
      transporter, GLUT1, in cytologic preparations of body cavity effusions and
      washes. With the use of standard avidin-biotin immunostaining for GLUT1, we
      examined cell blocks of body cavity effusions or washings from 31 carcinomas, 1
      lymphoma, and 25 benign effusions or washes. GLUT1 staining occurred in the
      malignant cell population in 29 (93.5%) of 31 carcinomatous effusions or washes.
      The characteristic staining pattern consisted of dense, linear staining of the
      plasma membrane, with accentuation at cell-cell borders, with or without
      cytoplasmic staining. Erythrocytes showed positive GLUT1 membrane staining,
      consistent with previous reports. Of 25 benign effusions, 20 were nonstaining
      (excepting erythrocytes), and 5 contained rare single mesothelial cells, with
      equivocal to very weak membrane staining. Staining of these cells was readily
      distinguishable from the characteristic strong staining of malignant cells, and
      these cells were easily distinguished from tumor cells by their benign
      morphologic characteristics. At least three of these latter five specimens were
      from patients with cirrhosis. In all of the other cases, mesothelial cells,
      histiocytes, and other inflammatory cells did not stain. These findings suggest
      that GLUT1 immunostaining could be useful in diagnostic cytopathology. The
      findings also suggest that enhanced glycolysis, which requires increased glucose
      transport, might be a survival adaptation for tumor cells in effusions, a
      significant number of which are hypoxic.

PMID- 9578092
TI  - Trichinellosis (trichinosis) is caused by the aphasmid nematode, Trichinella
      spiralis.

PMID- 9578093
TI  - Supratentorial giant cell ependymoma: a case report.
AB  - Ependymomas are neoplasms of the central nervous system that are capable of
      demonstrating remarkably heterogeneous histologic features. These tumors
      originate from ependymal cells lining the ventricles, the choroid plexus, the
      central canal of the spinal cord, and the filum terminale, so they are therefore
      seen throughout the neuraxis. We describe the case of a 26-year-old man who
      experienced a 3-week history of right-sided numbness and a 1-week history of
      worsening bifrontal headache. Computed tomographic scanning and magnetic
      resonance imaging of his head demonstrated an irregularly enhancing mass
      involving the left medial frontal lobe, with extension across the corpus callosum
      and expansion into the body and atrium of the left lateral ventricle. Histologic,
      immunohistochemical, and electron microscopic findings were consistent with an
      anaplastic ependymoma. Unique to this neoplasm was the presence of multiple tumor
      giant cells. The presence of pleomorphic tumor giant cells is a characteristic
      feature of the subependymal giant cell astrocytoma, and it is also commonly seen
      in pleomorphic xanthoastrocytoma and glioblastoma multiforme. Bizarre giant cells
      were recently described in two filum terminale ependymomas. This report presents
      the first case of a supratentorial giant cell ependymoma with anaplastic
      features.

PMID- 9578094
TI  - Primary hepatic low-grade B-cell lymphoma of mucosa-associated lymphoid tissue
      (MALT) associated with primary biliary cirrhosis.
AB  - We describe a case of low-grade B-cell lymphoma of mucosa-associated lymphoid
      tissue (MALT) arising in the liver of a patient with early-stage primary biliary
      cirrhosis (PBC). The patient, a 62-year old woman, presented with abnormal liver
      function tests, a positive antimitochondrial antibody titer (1:160), and a liver
      mass. The resected mass, 6.0 x 5.0 x 4.0 cm, had the features of MALT-type
      lymphoma. The neoplastic cells were small lymphoid cells of B-cell lineage that
      surrounded reactive lymphoid follicles and infiltrated bile ductules to form
      lymphoepithelial lesions. The uninvolved liver had histologic evidence of early
      stage PBC, characterized by segmental duct destruction with granulomata and an
      inflammatory infiltrate in the portal triads composed of lymphocytes, plasma
      cells, and occasional eosinophils. A periportal lymph node showed histologic
      features of the hyaline-vascular type of Castleman's disease, without evidence of
      malignant lymphoma. Low-grade B-cell lymphomas of the MALT type rarely arise in
      the liver and, to our knowledge, have not been reported previously in association
      with PBC. The association in this case suggests that chronic antigenic
      stimulation as a result of PBC induced the accumulation of acquired MALT, which
      subsequently transformed to low-grade B-cell lymphoma.

PMID- 9578095
TI  - Archetypes of the collective (medical) unconscious.

PMID- 9578096
TI  - Late results of subtalar distraction fusion.
AB  - Between 1990 and 1994, 15 subtalar distraction fusions were performed on 14
      patients for sequelae of calcaneus fractures. Twelve patients (13 feet) were
      available for a minimum 2-year follow-up and constituted the composition of this
      study. All patients complained of lateral ankle pain and had CT evidence of
      calcaneofibular abutment and radiographic evidence of loss of heel height
      preoperatively. The average age at time of surgery was 56 years (range, 23-81
      years), and the average follow-up was 47 months (range, 25-75 months). The only
      change in surgical technique from that previously described was the use of a bone
      spreader rather than a femoral distractor for distraction of the subtalar joint.
      The average preoperative talocalcaneal angle improved from 27 degrees range, 19
      37 degrees) to 33 degrees (range, 23-45 degrees) postoperatively (P < 0.003). The
      mean talar declination angle improved from 11 degrees (range, 6-18 degrees) to 16
      degrees (range, 7-27 degrees) postoperatively (P < 0.003). The mean heel height
      increased from 71 mm (range, 60-83 mm) to 76 mm (range, 63-91 mm) postoperatively
      (P < 0.0001). All patients completed the AOFAS Ankle-Hindfoot scale at latest
      follow-up, and the average score was 76.1 (range, 57-94). Eleven of 13 outcomes
      were rated as very satisfactory or satisfactory. Twelve of 13 said they would
      'definitely yes" do surgery again. We have found that subtalar distraction fusion
      for late complications of calcaneus fracture in a carefully selected population
      can provide a consistent and satisfactory outcome.

PMID- 9578097
TI  - Reconstruction operations for acquired flatfoot: biomechanical evaluation.
AB  - A major limitation of operations commonly performed for acquired flatfoot is
      inadequate correction of alignment. The authors defined the efficacy of two
      operations, deltoid ligament reconstruction and flexor digitorum longus tendon
      transfer, for treatment of posterior tibial tendon dysfunction with flatfoot
      deformity. Twelve fresh-frozen foot specimens were used. A flatfoot deformity was
      created, and, to simulate the midstance phase of gait, loads were applied axially
      to the plantar surface of the foot and to appropriate tendons. Foot position
      improved substantially after deltoid ligament reconstruction but not after flexor
      digitorum longus tendon transfer. The average increase in arch height after
      deltoid ligament reconstruction was 10.3 +/- 8.9 mm and after flexor digitorum
      longus tendon transfer, -0.6 +/- 2.0 mm. Mean arch height after deltoid ligament
      reconstruction was 2.2 +/- 1.7 mm less than intact arch height and, after flexor
      digitorum longus tendon transfer, 13.2 +/- 9.0 mm less than intact arch height.
      Improvement in metatarsal-talar, calcaneal-talar, and talar-tibial positions was
      significantly greater after deltoid ligament reconstruction than after flexor
      digitorum longus tendon transfer. Although the authors do not advocate clinical
      use, the deltoid ligament reconstruction was more effective than flexor digitorum
      longus tendon transfer in restoring arch alignment in flatfoot.

PMID- 9578098
TI  - Treatment of displaced pylon fractures with circular external fixators of
      Ilizarov.
AB  - Twenty cases of pylon fractures were treated with IIizarov circular external
      fixators using the technique of ligamentotaxis. Fourteen men and six women,
      ranging in age from 20 to 59 years, with open or closed distal tibial fractures
      were included in this study. The fractures were classified according to the AO
      system and distributed as seven C1, eight C2, and five C3 fractures. Independent
      from the type of fracture, six were grade II open according to the Gustilo
      Anderson classification. For all fractures, an external fixator was constructed,
      after reduction by traction and olive wires. Mean follow-up was 29 months. All
      fractures healed by 14 weeks postreduction. The results were assessed using
      Weber's criteria: 5 (25%) had excellent results, 10 (50%) good, and 5 (25%) poor
      results. This technique lowers the rated complications of open reduction and
      internal fixation, and allows restoration of joint-surfaces, reconstruction of
      length, and alignment of the extremity while maintaining a sufficient range of
      motion at the joint. We concluded that use of the Ilizarov circular external
      fixator enables good results in selected ankle traumas when applied with good
      indications, planning, and surgical experience.

PMID- 9578099
TI  - Use of ready-made insoles in the treatment of lesser metatarsalgia: a prospective
      randomized controlled trial.
AB  - Two insoles designed to treat primary lesser metatarsalgia were compared in terms
      of their effect on plantar pressures and the subjective symptom relief. A
      prospective single blind randomized trial of 8 weeks' treatment in 46 feet in 33
      patients was performed. Subjective outcome measures were visual analogue pain
      scores and estimated compliance. Objective outcome measures were dynamic plantar
      pressures using the Musgrave Footprint System. In group 1 (Viscoped), 6 of 18
      patients rated themselves much improved or somewhat improved, and in group 2
      (Langer) the proportion was 12 of 15 (P = 0.02). Reported mean compliance was 16%
      higher in the Langer group. Plantar forefoot pressure was lowered by the insoles
      in all cases. The reduction was significantly greater (P < 0.001) in group 2,
      both in absolute pressure and as a percentage of initial pressure. Group 2
      (Langer) was significantly better in terms of reduction of peak metatarsal
      pressure. All the subjective outcome measures were better for the group 2
      (Langer).

PMID- 9578100
TI  - Insufficiency stress fractures of the foot and ankle in postmenopausal women.
AB  - Eleven consecutive patients with 12 stress fractures of the foot or ankle were
      seen between October 1992 and July 1995. Charts were reviewed retrospectively for
      clinical information. The patients were all postmenopausal females. Average age
      was 62 years. Onset of symptoms was not associated with a specific episode of
      trauma. There were eight metatarsal fractures, three distal fibular fractures,
      and one fracture of the medial malleolus. Fractures were confirmed by
      radiographs, bone scan, or MRI in 9 of the 11 cases. Nonsurgical treatment
      utilizing rest, decreased activity, mechanical support, and analgesics resulted
      in successful union of the fracture except in one patient. Only four of the
      patients had been taking hormone or calcium supplements before injury. Just one
      patient had a prior bone density measurement, although four had a definite
      fracture previously and two had history suggestive of previous stress fracture. A
      careful history considering risk factors for osteoporosis should be obtained when
      an insufficiency type stress fracture is diagnosed. Bone density measurements
      should be considered for patients with this type of injury. Appropriate medical
      therapy directed at the treatment of the underlying osteoporosis in addition to
      orthopaedic management of the fracture constitute the treatment objectives. This
      dual approach may prevent subsequent injury.

PMID- 9578101
TI  - Paget disease of the calcaneus: findings on MR imaging.

PMID- 9578102
TI  - Operative management of foot and ankle equinovarus associated with focal
      dystonia.
AB  - Six surgical procedures, consisting of tendon transfers and releases, were
      performed in five patients with idiopathic focal dystonia involving the lower
      extremity. All patients were female. Surgical management was performed to correct
      clinically significant foot abnormalities. The goal of each procedure was
      functional improvement and obtaining a plantigrade foot. The SPLATT (split
      anterior tibial tendon transfer) procedure was performed in each foot with a
      flexible equinovarus foot abnormality. Follow up at a mean of 27.2 months (range,
      8-40 months) yielded satisfactory clinical results without significant
      complications. Clinical equinovarus has not recurred after this procedure. All
      patients remain brace-free ambulators.

PMID- 9578103
TI  - Elongation behavior of calcaneofibular and cervical ligaments during inversion
      loads applied in an open kinetic chain.
AB  - The cervical ligament plays a significant role in lateral stability of the
      subtalar joint but has received little attention compared with other ankle and
      subtalar joint ligaments. The purpose of this research was twofold. First, the
      elongation behavior of the cervical ligament was assessed with the
      calcaneofibular ligament intact and cut during two different types of inversion
      loads (manual and mechanical). Second, inversion range of motion was determined
      concomitantly with inversion loading and the difference in inversion range of
      motion between the calcaneofibular ligament intact to cut state was compared. The
      mean elongation of the cervical ligament with the calcaneofibular intact was 0.58
      mm (+/- 0.33 mm) and 0.46 mm (+/- 0.23 mm) for manual and mechanical methods,
      respectively, and 0.88 mm (+/- 0.37 mm) and 0.78 mm (+/- 0.37 mm), respectively,
      for the same methods in the absence of the calcaneofibular ligament. This
      difference was statistically significant (P < 0.05 manually and P < 0.02
      mechanically). An average increase in the inversion range of motion was noted
      with both methods [7.5 degrees manually (+/- 2.75 degrees) and 7.7 degrees
      mechanically (+/- 2.95 degrees)] after lesioning of the calcaneofibular ligament.
      This difference was statistically significant (P < 0.001) for both manual and
      mechanical range of motion testing. The results of this study indicate that there
      is a significant increase in elongation of the cervical ligament in the absence
      of the calcaneofibular ligament during manual and mechanically applied inversion
      loads in a open kinetic chain. Clinical and theoretical implications of this data
      are discussed.

PMID- 9578105
TI  - Lipoma of the toe.
AB  - Lipoma is a common benign soft tissue tumor. It may arise in any location, but
      most frequently it is located on the trunk, chest, upper thigh, upper arm, and
      shoulder. Reports of a lipoma in the foot exist, but the occurrence of the tumor
      in this location is very rare. Lipomas of the toe have only been reported in
      children, some imitating or having associated gigantism. We present a benign
      lipoma occurring on the plantar aspect of the second toe in an adult.

PMID- 9578104
TI  - Arthrodesis of the ankle secondary to replacement.
AB  - One hundred total ankle arthroplasties were performed in our department between
      1974 and 1994, and of these, 21 have been reoperated on with arthrodesis due to
      septic or nonseptic failures after 6 months to 15 years (median 40 months).
      Immobilization using a Hoffman external fixator was the dominating method. The
      total ankles were of six different designs. Sixteen of the 21 patients suffered
      from rheumatoid arthritis. Four of the 21 ankles did not fuse whereas 17 did: 13
      at the first attempt and 4 after repeat arthrodesis. At the time of the review,
      two patients had died. Of the remaining 15 patients whose ankles had fused, all
      but one were satisfied or somewhat satisfied with the result. Twelve of these 15
      ankles rated excellent or good according to the Mazur and Kofoed scoring systems.
      We conclude that arthrodesis can be performed successfully after a failed ankle
      arthroplasty.

PMID- 9578106
TI  - A calcaneal fracture with extrusion of the posterior facet.
AB  - This is a case report of a 19-year-old woman who sustained multiple fractures
      including a right calcaneal fracture with extrusion of the posterior facet. The
      medial soft-tissue injury led to a full thickness skin loss. Despite loss of
      subtalar motion and decreased toe movement, she is satisfied with her result. The
      importance of the soft-tissue injuries, especially to the skin and tendons,
      associated with severely displaced calcaneal fracture dislocations is emphasized
      by this case report.

PMID- 9578107
TI  - Osteochondral lesions of the proximal phalanx of the great toe: a report of two
      cases.
AB  - Two cases of osteochondral lesions of the proximal phalanx of the great toe at
      the interphalangeal joint are presented. This condition is characterized by pain,
      swelling, and tenderness at the interphalangeal joint. The roentgenographic
      characteristics resemble osteochondritis dissecans. Curettage and bone grafting
      to the lesion is effective. These conditions in adolescent soccer players may be
      caused by chronic repetitive overloading of the interphalangeal joint using
      soccer shoes with soft, supple, and narrow toe boxes.

PMID- 9578108
TI  - Case report: fracture of the posterior medial tubercle of the talus secondary to
      direct trauma.
AB  - Isolated fracture of the posterior medial tubercle of the talus is a rare injury,
      generally thought to result from a pronation-dorsiflexion force causing avulsion
      of the insertion of the posterior talotibial ligament. Originally described by
      Cedell, the fracture has subsequently been reported three times to our knowledge,
      with all cases being attributed to indirect trauma. We describe an isolated
      fracture of the posterior medial tubercle of the talus caused by direct trauma.
      The fracture of the posterior medial tubercle remained ununited, failed to
      respond to conservative therapy, and was treated successfully with surgical
      excision.

PMID- 9578109
TI  - Bilateral peroneal tubercle osteochondroma of the calcaneus: case report.
AB  - A case of bilateral symmetric osteochondroma of the peroneal tubercle in a 24
      year-old woman is presented. This lesion is discussed along with its etiology and
      related findings.

PMID- 9578110
TI  - Longevity of exercising male rats: effect of an antioxidant supplemented diet.
AB  - Food restriction increases maximal life span in rodents. Male rats that exercise
      in voluntary running wheels do not have an increase in maximal longevity despite
      a relative caloric deficit. In contrast, sedentary rats that are food restricted
      so as to cause the same caloric deficit have an extension of maximal longevity.
      It seemed possible that exercise-induced oxidative stress might prevent a maximum
      life span-extending effect of a caloric deficit to manifest itself. This study
      was done to determine if antioxidants would allow a maximal longevity-extending
      effect of exercise to manifest itself in male rats. The antioxidant diet had no
      effect on longevity of the runners (Antiox., 951 +/- 158 days versus control 937
      + 171 days), or of the sedentary controls (875 +/- 127 versus 858 +/- 152 days).
      As in previous studies, wheel running modestly increased average longevity
      (approximately 9%), but had no effect on maximal life span. The finding that
      antioxidants had no effect on longevity of the wheel runners supports the
      interpretation that the caloric deficit induced by exercise in male rats does not
      have a life-extending effect that is countered by oxidative tissue damage.

PMID- 9578111
TI  - Age-dependent accumulation of advanced glycation end-products in adult Drosophila
      melanogaster.
AB  - Advanced glycation end-product(s) (AGE) are formed in biological systems when
      reducing sugars react with amino groups on proteins. Long-lived proteins such as
      collagen and lens crystallins are known to be susceptible to AGE modification and
      may play a major role in the development of diabetes and other age-related
      pathologies. It has been previously suggested that AGE formation might affect the
      lifespan of experimental animals. Our study is the first to examine the effect of
      AGE accumulation on the life span of an organism, Drosophila melanogaster. We
      found that Drosophila melanogaster maintained at 24 degrees C accumulate
      significant AGE over their lifespan. Young flies (10 days old) had 44% less AGE
      than senescent flies (75 days old). We were able to reduce AGE accumulation in
      Drosophila melanogaster by raising the flies on a medium containing a known AGE
      inhibitor, aminoguanidine HCl. Reduction of AGE in flies failed to increase their
      mean lifespan, and high concentrations (40 mM) reduced the mean life span, which
      suggests that aminoguanidine is toxic at levels near those required for
      inhibition of AGE formation. However, the common fruit fly, Drosophila
      melanogaster, provides a simple model system to study the age-dependent
      accumulation of glycated proteins and their inhibition by novel compounds.

PMID- 9578112
TI  - Age-associated oxidative damage in microsomal and plasma membrane lipids of rat
      hepatocytes.
AB  - Phosphatidylcholine hydroperoxide (PC-OOH) and phosphatidylethanolamine
      hydroperoxide (PE-OOH) concentrations were determined in microsomes and plasma
      membranes prepared from 2- and 17-month-old male Sprague-Dawley rat hepatocytes,
      to verify the dissimilarity of age dependency of lipid peroxidation in organelle
      membranes. The hydroperoxides were directly measured by chemiluminescence
      detection-high-performance liquid chromatography (CL-HPLC), and 1-palmitoyl-2-(13
      hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH) and 1
      palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl)
      phosphatidylethanolamine (PLPE-OOH) were enzymatically synthesized and utilized
      as standards for the calibration. Baseline concentrations of hydroperoxides (PC
      OOH + PE-OOH) of the 17-month-old rats were 46 pmol per mg protein in microsomes
      (2.7 times higher than the 2-month-old rats) and 306 pmol per mg protein in
      plasma membranes (9.9 times higher than the 2-month-old rats). Both microsomal
      and plasma membrane lipids were severely peroxidized and converted to
      phospholipid hydroperoxides by NADPH-dependent lipid peroxidation in vitro, but
      the age-dependency was only observed in the plasma membranes. These results
      demonstrate that substantial oxidative damage to membrane phospholipids occurs
      with ageing both in microsomes and plasma membranes, but is more prevalent in
      plasma membranes in rat hepatocytes.

PMID- 9578113
TI  - Influence of physical exercise on aging rats. III. Life-long exercise modifies
      the aging changes of the mechanical properties of limb muscle tendons.
AB  - We have previously shown that long-term regular physical exercise has a systemic
      influence on the rat by slowing the aging of its connective tissues, measured as
      thermal stability and biomechanical properties of tail tendons. This paper
      analyses whether the properties of limb muscle tendons are influenced not only by
      the aging process and the systemic effects of exercise but also from direct
      mechanical stimuli from long-term physical exercise. Male Sprague-Dawley rats
      were trained in a treadmill from the age of 5 to 23 months. The effects of
      training on muscle tendons were analyzed with respect to biomechanical
      properties. Also, the viscoelastic activation energies for interactions between
      collagen and the proteoglycan gel as well as between collagen fibrils were
      measured. Finally the asymptotes from the creep curves were calculated in order
      to estimate the magnitude of the viscoelastic creep. The effects of aging were
      analyzed with respect to the same parameters by comparing the group of 23-month
      old sedentary rats with a 5-month-old baseline group. The biomechanical
      parameters did not change significantly with physical exercise. Neither did the
      activation energies change, but the asymptotes of the creep curves decreased,
      showing that there was less viscoelastic creep. Aging rendered the tendons
      significantly stronger and stiffer, increased the energy-absorbing capacity and
      decreased the strain values. The activation energies did not change with aging,
      but the high creep curve asymptote for the flexor tendons decreased. We conclude
      that aging rendered both types of tendons stiffer, and decreased their strain
      values at breaking point. Aging also increased the stress value, the energy
      absorption and the dry weight for the flexor tendon. Further, while physical
      exercise has a systemic delaying effect on age changes in connective tissues, in
      tendons subjected to substantial mechanical loads this effect as measured with
      biomechanical methods is counteracted by the optimization process elicited by the
      same physical exercise.

PMID- 9578114
TI  - Glyoxalases activity during Bufo bufo embryo development.
AB  - In this work we have investigated the expression of glyoxalase I (GLO I) and
      glyoxalase II (GLO II) activities during Bufo bufo embryo development and in some
      tissues of both male and female adult animals, in order to study how they
      correlate with cell proliferation and differentiation. The results show that both
      the activities are expressed at significant levels from the earliest
      developmental stages, reaching the highest values at the end of embryonic
      development (stage 25). The GLO I/GLO II ratio is very high at the beginning of
      the development and then gradually decreases as the development goes on. These
      data emphasize the importance of GLO I activity in the phases in which elevated
      cell division is taking place. In the differentiated tissues, a peculiar sexual
      dimorphism in both GLO I and GLO II activities, with higher values in female than
      in male, was found. GLO I embryonic activity levels are comparable to those found
      in female differentiated tissues, but significantly higher than those detected in
      male differentiated tissues. On the contrary, the GLO II activities found in the
      adult tissues were always higher than those found in embryos. These results
      further support the idea that high GLO I/GLO II ratios are a characteristic of
      the proliferative status, which assures a good scavenging action against the
      potentially cytotoxic and cytostatic effect of methylglyoxal.

PMID- 9578115
TI  - Nonrandom sequence of slope-intercept estimates in longitudinal gompertzian
      analysis suggests biological relevance.
AB  - The significance of intersections in age-specific mortality rate distributions
      could be attributed to a fundamental statistical relationship between estimates
      of slope and intercept. A strong negative correlation between estimates of slope
      and intercept is often observed in simple linear regression problems. The net
      result is that the family of lines generated by repetitive estimates of slope and
      intercept in a static experimental situation will tend to intersect at a common
      point. This statistical relationship between slope and intercept, however, should
      be random with respect to the time-ordered sequence of slope and intercept
      estimates. Annual paired slope and intercept estimates derived using the method
      of longitudinal Gompertzian analysis of age-specific mortality rates for men and
      women in the United States from 1900 to 1988 were analyzed to determine if they
      varied randomly. The probability that the observed sequence in these annual
      paired slope-intercept estimates was random is less than 10(-50) for both men and
      women. This finding essentially excludes the possibility that intersections in
      age-specific mortality rate distributions reflect a fundamental statistical
      relationship between slope and intercept and further suggests biological
      relevance for the method of longitudinal Gompertzian analysis.

PMID- 9578116
TI  - Beta-adrenergic and muscarinic receptor mRNA accumulation in the sinoatrial node
      area of adult and senescent rat hearts.
AB  - The sinoatrial (SA) node is the cardiac pacemaker and changes in its adrenergic
      muscarinic phenotype have been postulated as a determinant of age-associated
      modifications in heart rate variability. To address this question, right atria
      were microdissected, the SA node area was identified by acetylcholinesterase
      staining, and, using a RT-PCR method, the accumulation of mRNA molecules encoding
      beta1- and beta2-adrenergic (beta1- and beta2-AR) and muscarinic (M2-R) receptor
      was quantified to define the proportion between beta-AR and M2-R mRNAs within the
      sinoatrial area of adult (3 months) and senescent (24 months) individual rat
      hearts. In adult hearts, the highest M2-R/beta-AR mRNA ratio was observed within
      the sinoatrial area compared with adjacent atrial myocardium, while in the
      senescent hearts, no difference was observed between sinoatrial and adjacent
      areas. This change was specific of the sinoatrial area since adult and senescent
      whole atrial or ventricular myocardium did not differ in their M2-R/beta-AR mRNA
      ratio, and was associated with a fragmentation of acetylcholinesterase staining
      of the senescent SA node. Quantitative changes in the expression of genes
      encoding proteins involved in heart rate regulation specifically affect the
      sinoatrial area of the senescent heart.

PMID- 9578118
TI  - Increase of interleukin 6 and decrease of interleukin 2 production during the
      ageing process are influenced by the health status.
AB  - The ageing process is accompanied by the disregulation of interleukin 2 (IL2) and
      interleukin 6 (IL6) production. In our paper, we asked whether the age between 60
      and 70 years is a turning point for the disregulation of both IL2 and IL6
      production. Fifty volunteers 60-70 years old, 25 aged 36-59, and 50 of 20-35
      years old were enrolled into the study. Their health status was graded according
      to the criteria of the Senieur Protocol (SP) as 'healthy' and 'almost-healthy'.
      The cytokines level was determined in the sera of the volunteers. Moreover, the
      spontaneous release of IL6 by peripheral blood mononuclear cells (PBMC) and the
      activity of the IL6 gene in non-stimulated PBMC were also analysed. Cytokine
      levels were measured by biological assays, mRNA for IL6 was detected by RT-PCR
      method. The results showed that the production of IL2 is not disregulated in the
      'healthy' people until the age of 60-70. People not fulfilling all SP criteria
      are characterised by a lower level of IL2 in the sera. The overproduction of IL6
      into the sera and supernatants from non-stimulated PBMC and PBL as well as the
      activation of IL6 gene start between the ages 36 and 59 and is more pronounced in
      the 'almost-healthy'.

PMID- 9578117
TI  - Neuron and glial cells in neocortex after methylazoxymethanol treatment in early
      development.
AB  - The quantitative changes were investigated in neuron and glia density in the
      different cortical layers of the frontal cortex of 3 and 12 month old mice,
      exposed to methylazoxymethanol on embryonic day 13 (MAM13). No loss of cortical
      neurons was found between young and adult animals. MAM exposure on the 13th day
      of development induced a neuron density decrease throughout on the entire
      cortical depth and did not produce changes in the density of glial cells with
      respect to the controls and to age. Consequently, at 3 months of age we observe a
      glia/neuron ratio greater than that of controls and at 12 months a similar value.
      In the neocortex of MAM-mice at this numerical uniformity of glial cell density,
      did not correspond to a similar proportional composition: the frequency of the
      astrocytes is lower, adapting to the decreased neuron density; the greater
      oligodendrocyte percentage may be related to disturbed layering and to the
      hyperinnervation of the hypoplastic cortex; the microglia shows a trend similar
      to that of the controls. These results, together with those of other studies,
      suggest that prenatal exposure to MAM causes a cortical compensatory response
      regulating glial cells proliferation.

PMID- 9578119
TI  - Pathophysiological and therapeutic considerations of otitis media with effusion
      from viewpoint of middle ear ventilation.
AB  - Using nitrous oxide, we examined the gas exchange function through the middle ear
      mucosa in ears with otitis media with effusion (OME) in children, and found the
      function to be impaired in 50% of them. The size of the mastoid was significantly
      smaller in ears with negative gas exchange function than those with positive
      function, and the presence or absence of the function was even more significantly
      correlated with the presence or absence of aeration in the middle ear.
      Furthermore, the presence or absence of aeration in ears with OME was found to be
      significantly correlated with their prognosis (response of OME to antibiotics
      treatment) and also with the presence or absence of eardrum mobility examined by
      a pneumatic otoscope. Finally, after myringotomy and removal of effusion, the gas
      exchange function recovered in most of the ears with impaired function. These
      results indicate that the eardrum mobility test may serve as an appropriate
      indicator for the surgical treatment for OME.

PMID- 9578120
TI  - Electrocautery versus curette adenoidectomy: comparison of postoperative results.
AB  - OBJECTIVE: Identify differences in adenoidectomy performed by curettage versus
      electrocautery ablation. DESIGN: To receive adenoidectomy by curettage or
      electrocautery ablation 38 patients undergoing adenoidectomy or
      adenotonsillectomy were prospectively randomized. The study was completed by 24
      patients. All tonsillectomy patients received electrocautery dissection of the
      tonsils. Preoperative and at least 1 month postoperative video-nasopharyngoscopy
      was performed. Video tapes were reviewed by the authors blinded to patient
      identity and procedure to evaluate choanal obstruction. Preoperative and
      postoperative lateral neck radiographs were obtained. Blood loss and
      postoperative complications were recorded. SETTING: A single, tertiary care
      pediatric facility. INTERVENTIONS: Electrocautery ablation of the adenoid was
      performed with suction cautery. Curettage was performed with standard adenoid
      curettes. MAIN OUTCOME MEASURED: A grading system for adenoid size was developed
      using radiographs and endoscopic parameters. The grade of preoperative and
      postoperative adenoid tissue was compared between the curettage and
      electrocautery ablation groups. Operative blood loss was compared between the
      groups. The postoperative course and complications were compared. RESULTS: The
      preoperative grade of choanal obstruction in both groups was the same. No
      differences could be found in the postoperative grade between the curettage and
      the electrocautery ablation groups. No postoperative complications were recorded
      in either group. The estimated blood loss in the curettage group was 54.5 ml
      (S.D. 50.7) while the electrocautery ablation group averaged 3.75 ml (S.D. 6.4; p
      = 0.0053). CONCLUSION: There are no differences in the postoperative results of
      adenoidectomy performed by electrocautery ablation or curettage. There are no
      complications recorded in either group. Estimated blood loss was lower in the
      electrocautery ablation group. Decreased blood loss during the procedure makes
      the electrocautery ablation method of adenoidectomy attractive.

PMID- 9578121
TI  - Middle ear disease in cystic fibrosis.
AB  - A prospective cross-sectional study was done to investigate the involvement of
      middle ear disease in cystic fibrosis. Eighty-eight patients with cystic
      fibrosis, aged 1-28 years, were examined during the winter period 1995-1996 at
      regular follow-up visits to detect history and prevalence of inflammatory and
      infectious middle ear disease by questionnaire, otoscopy and tympanometry. One
      third of the patients had a history of otitis media, but only in 9% did this
      occur more than once. Hearing problems were recorded in 8%, but this was severe
      in only one case. Otoscopy showed 141 normal tympanic membranes, 17 times
      retraction, 15 times otitis media with effusion, once an acute otitis media in
      both ears. Only one patient had a grommet in one ear. More than 70% of the
      tympanograms were normal. A flat curve, type B according to Jerger's
      classification, was found in 11 ears. The youngest age group had a higher
      prevalence of abnormal findings on otoscopy and tympanometry, while patients who
      had undergone paranasal sinus surgery had less frequently abnormal findings. In
      conclusion, no evidence that cystic fibrosis is associated with increased
      prevalence of middle ear disease has been found in this prospective cross
      sectional study.

PMID- 9578122
TI  - Glucose 6-phosphate dehydrogenase deficiency with kernicterus: progressive late
      recovery from profound deafness.
AB  - In this case report a near-term infant with Glucose 6-Phosphate Dehydrogenase (G6
      PD) deficiency had an unconjugated bilirubin level of 703 on the 11th day of life
      but maintained his haemoglobin levels above 11 gm/dl. At 4 months of age he
      demonstrated the clinical picture of Kernicterus: profound sensorineural deafness
      and evidence of encephalopathy. However, by 15 months of age his abnormal
      cerebral and motor signs had regressed to a near-normal level in parallel with a
      gradual improvement in hearing, which also reached normal levels, first in the
      right ear, then in the left. At this age residual mental retardation has not been
      excluded but his communication skills, though delayed by 4-6 months, were moving
      towards the level when they would be appropriate for his age.

PMID- 9578123
TI  - Neonatal suppurative submandibular sialadenitis: a rare clinical entity.
AB  - Submandibular sialadenitis is very rare in the neonatal age group. Only four
      cases of isolated submandibular gland infection without the involvement of the
      parotid gland have been reported in the literature up to the present time. We
      present a case of a premature newborn infant who developed fever and right
      submandibular swelling when he was 8 days old. Pus was found extruding from
      Wharton's duct. The pus culture yielded Pseudomonas aeruginosa. The patient was
      treated conservatively with adequate hydration and intravenous ceftazidime for 14
      days and the infection resolved. The possible predisposing factors were
      dehydration and prematurity. CT scan revealed no calculi and no anatomic
      derangement. Two months follow-up showed no evidence of recurrence. Previous
      literature is reviewed and discussed.

PMID- 9578124
TI  - Sinusitis-associated epidural abscess presenting as posterior scalp abscess--a
      case report.
AB  - Complications of paranasal sinusitis constitute true surgical and medical
      emergencies. These complications appear to be more prevalent and seem to present
      in a more fulminant manner in the pediatric age group. The most common
      complication of paranasal sinusitis is orbital cellulitis followed collectively
      by all the intracranial complications. These include meningitis, subdural
      empyema, intracerebral abscess, epidural abscess and rarely cavernous or superior
      sagittal sinus thrombosis. We report the case of a 7-year old boy who presented
      with posterior scalp cellulitis and abscess as a complication of minimally
      symptomatic paranasal sinusitis. A combined neurosurgical and otolaryngologic
      approach was required to treat a unilateral ethmoid and frontal sinusitis
      associated with an epidural abscess abutting the length of the superior sagittal
      sinus and a posterior subgaleal abscess. The pertinent anatomy allowing for the
      development of this disease process is discussed. The danger of neurologic
      sequellae resulting from thrombosis of the superior sagittal sinus is emphasized.
      Aggressive treatment utilizing a multi-disciplinary surgical approach as well as
      broad spectrum antibiotics is paramount to obtain the best chance for a full
      recovery.

PMID- 9578125
TI  - Salivary gland heterotopia in the lower neck: a report of five cases.
AB  - Heterotopic salivary gland tissue (HSGT) represents an uncommon lesion, usually
      presenting as a discharging sinus in the base of the neck. Diagnostic criteria
      and embryogenesis of this entity still remain unclear. For the purpose of
      clarifying both subjects, all lateral cervical anomalies undergoing surgery
      during a 12-year period were examined. Histological study showed salivary tissue
      in 10 out of 119 patients. However, only 5 of them accomplished HSGT criteria.
      This study presents the second largest series to date of undisputed HSGT in the
      lower neck. Both accessory glands and branchial cleft anomalies should be
      distinguished from this lesion. Neoplastic transformation in HSGT, although
      extremely rare, should also be considered.

PMID- 9578127
TI  - Infantile cortical hyperostosis and facial nerve palsy.
AB  - Facial nerve palsy was diagnosed in a 13-month-old child with infantile cortical
      hyperostosis. Facial palsy preceded the roentgenographic evidence of mandibular
      hyperostosis but there was concurrent evidence of hyperostosis of multiple other
      bones. This case exemplifies the importance of maintaining a high index of
      suspicion for infantile cortical hyperostosis in infants and children presenting
      with facial swelling and facial nerve palsy.

PMID- 9578126
TI  - Squamous cell carcinoma of the trachea in an infant: a case report.
AB  - Primary malignant tumours of the trachea are extremely rare in infants. This
      report describes an 11-month-old boy suffering from severe dyspnea with a 5-month
      history of stridor and 'bronchitis'. A hard mass could be palpated below the
      right lobe of the thyroid gland. Roentgenograms and endoscopy showed an exophytic
      tumour filling more than 80% of the tracheal lumen. A tracheal resection and a
      subtotal thyroidectomy with primary anastomosis was performed. An invasive
      squamous cell carcinoma of the trachea was diagnosed. This is the first reported
      case in an infant in the English literature. A local recurrence was found on MRI
      19 weeks later. The infant died at 16 months of age.

PMID- 9578128
TI  - ABR and temporal bone pathology in Hurler's disease.
AB  - This is believed to be the first report on estimating hearing loss in Hurler's
      disease, based on the correlation between ABR and temporal bone pathology. ABR
      findings revealed hearing loss to be about 70 dB or more as result of peripheral
      mixed impairment. A histological study of the temporal bones revealed almost all
      pathological findings in the conductive system, except for the hyperplastic
      arachnoid in the internal auditory canal. In the middle ear cavity, otitis media,
      residual mesenchyme and deformity of ossicles were found. We explain the
      conductive component to be due to otitis media and poor ossicular connection.
      However, the etiology of the sensorineural component remains speculative. In
      Hurler's disease, hearing loss with mental retardation is often found at
      infantile age. Therefore, assessing the extent of hearing loss exactly was
      difficult, for example, the severity. the etiology and incidence of sensorineural
      impairment. We emphasize the need for not only well-described pathological
      studies but also for more objective functional investigations, at least ABR.

PMID- 9578129
TI  - Amusing parents while nature cures otitis media with effusion.

PMID- 9578130
TI  - Loss of human hippocampal adenosine A1 receptors in dementia: evidence for lack
      of specificity.
AB  - The density of hippocampal adenosine A1 receptors was measured in autopsy samples
      of six patients with dementia with either Alzheimer (three) or sclerosis type
      pathology (three) in hippocampus and six control patients. Kinetic parameters
      (Bmax and KD) were determined by means of quantitative autoradiography using
      [3H]8-cyclopentyl-1 ,3-dipropylxanthine as a radioligand. A significant 50%
      reduction of CA1 adenosine A1 receptors was observed in patients with dementia
      independent of the specific pathology. These results suggest that loss of
      hippocampal adenosine A1 receptors in dementia is not specific for Alzheimer type
      pathology.

PMID- 9578131
TI  - Distribution of hypoglossal motor neurons innervating the prehensile tongue of
      the African pig-nosed frog, Hemisus marmoratum.
AB  - Using retrograde neuronal tracers, a study of the distribution of hypoglossal
      motor neurons innervating the tongue musculature was performed in the African pig
      nosed frog, Hemisus marmoratum. This species is a radically divergent anuran
      amphibian with a prehensile tongue that can be aimed in three dimensions relative
      to the head. The results illustrate a unique rostrocaudal distribution of the
      ventrolateral hypoglossal nucleus and an unusually large number of motor neurons
      within this cell group. During the evolution of the long, prehensile tongue of
      Hemisus, the motor neurons innervating the tongue have greatly increased in
      number and have become more caudally distributed in the brainstem and spinal cord
      compared to other anurans. These observations have implications for understanding
      neuronal reconfiguring of motoneurons for novel morphologies requiring new muscle
      activation patterns.

PMID- 9578132
TI  - Herpes simplex virus encephalitis: long-term comparative study of viral load and
      the expression of immunologic nitric oxide synthase in mouse brain tissue.
AB  - In the brain tissue of 21 mice infected with herpes simplex virus type 1 (HSV-1)
      strain F we determined the expression of immunologic nitric oxide synthase (iNOS)
      as a potential mediator of neuronal injury with a semiquantitative reverse
      transcription polymerase chain reaction. Viral burden in brain tissue was
      quantitated with a dilutional polymerase chain reaction assay. Viral burden and
      iNOS-expression peaked at day 7 following infection. Thereafter viral burden
      declined to a low baseline value at 6 months following infection, whereas iNOS
      expression was still 4-fold increased compared to baseline levels. In
      experimental herpes simplex virus encephalitis iNOS, as one potent mediator of
      neuronal injury, is upregulated in the acute and chronic disease. In future, in
      addition to antiviral treatment, inhibitors of iNOS might offer new therapeutic
      strategies in herpes simplex virus encephalitis.

PMID- 9578133
TI  - Opposing effects of intracerebroventricularly injected norepinephrine on oxytocin
      and vasopressin neurons in the paraventricular nucleus of the rat.
AB  - Our previous study shows that intracerebroventricularly (i.c.v.) injected
      norepinephrine (NE) had different effects on the discharge of different firing
      patterns of magnocellular neurons in the paraventricular nucleus (PVN). In the
      present study we further classified antidromically identified magnocellular
      neurons into two groups: vasopressin (VP) and oxytocin (OT) secreting neurons,
      and found that of all 48 cases of magnocellular neurons, NE had mainly excitatory
      effects on 36 cases of putatively OT-secreting neurons, and inhibitory effects on
      12 cases of VP-secreting neurons. The third ventricular injected NE had almost
      the same effect on two types of neurons as that of lateral ventricular injection,
      partly ruling out the possibility that the lateral ventricularly injected NE may
      have acted indirectly on the magnocellular neurons in PVN. The results show that
      different mechanisms may be involved in mediating the effect of i.c.v. injected
      NE on VP- and OT-secreting neurons in the PVN.

PMID- 9578135
TI  - Effects of anesthetics on norepinephrine release in the hypothalamic
      paraventricular nucleus region of awake rats.
AB  - The effects of pentobarbital sodium, chloralose and urethane on norepinephrine
      (NE) release in the hypothalamic paraventricular nucleus (PVN) region were
      examined in awake rats. An in vivo microdialysis method was used. Extracellular
      NE concentrations in the PVN region were measured by high performance liquid
      chromatography with electrochemical detection. Pentobarbital sodium (30 mg/kg,
      intravenously [i.v.]) and chloralose (50 mg/kg, i.v.) caused a 30-40% decrease in
      NE release while urethane (800 mg/kg, i.v.) caused a 50% increase. Plasma NE
      concentration was not altered after pentobarbital sodium and chloralose
      administrations, except for its increase in chloralose at 5 h, while the
      concentration increased significantly (P < 0.01) after urethane. These results
      suggest that, in the rat, these anesthetic agents have different effects on
      noradrenergic activity in the PVN region as well as on plasma NE.

PMID- 9578134
TI  - Tryptophan and its metabolite, kynurenine, stimulate expression of nerve growth
      factor in cultured mouse astroglial cells.
AB  - Effects of L-tryptophan and its metabolites were evaluated on expression of nerve
      growth factor (NGF) in primary culture of mouse astroglial cells. L-Tryptophan
      produced concentration-dependent increases in accumulation of NGF transcripts in
      the cells. L-Kynurenine, a metabolite of the kynurenine pathway, markedly
      increased the levels of mRNAs for NGF, the maximal increases (4-5 fold) occurred
      at its dose of 1 microM. Kynurenine-induced increase in mRNA levels for NGF
      occurred as early as 1 h after the addition of the compound, peaked at 4 h and
      declined thereafter. In contrast to kynurenine, other tryptophan metabolites such
      as quinolinic acid, kynurenic acid and serotonin had little effect on the levels
      of NGF mRNA.

PMID- 9578136
TI  - Cortical anesthesia reduced the amplitude of local P300 event-related potential
      in rabbits by auditory oddball paradigm.
AB  - Eight rabbits were employed in this study. Under anesthesia, one electrode was
      fixed in the skull at the bregma and another was fixed, with three guide cannulas
      around it, at a parietal point 5 mm lateral to the bregma. Two weeks later, with
      a 10-day interval, either 0.5% lidocaine (9 microl) or the same volume of normal
      saline was injected into cortex through the cannulas. Event-related potentials
      (ERPs) evoked by auditory oddball paradigm were recorded before and after the
      injections in alert rabbits. The probability of occurrence for the 2 and 1 kHz
      stimulus tones was 90% (frequent) and 10% (rare), respectively. After lidocaine
      injection, P3 amplitude to rare stimuli decreased to 37.6% (P < 0.05), while N1
      did not show any significant changes. ERPs from the bregma were intact. P3 and N1
      did not change after normal saline injection. Our results show that local
      parietal cortex is one of the P3 generators.

PMID- 9578137
TI  - Age differences in the expression of metabotropic glutamate receptor 1 and
      inositol 1,4,5-trisphosphate receptor in mouse cerebellum.
AB  - Age differences in the expression of cerebellar metabotropic glutamate receptor 1
      (mGluR1) and inositol 1,4,5-trisphosphate receptor (IP3R) were investigated using
      male C57BL/6NNIA mice 5, 15 and 24 months of age. In situ hybridization for
      mGluR1 mRNA in the granule cell layer indicated significantly higher mRNA levels
      in the 24-month-old group as compared to the 5- and 15-month-old groups. However,
      mRNA levels of individual Purkinje neurons did not show age differences. Western
      blot analysis using antibody against the predominant isoform, mGluR1a, showed a
      decline in protein levels in the 24-month-old animals. In situ hybridization for
      IP3R type 1 mRNA in Purkinje neurons showed a slight but not significant decline
      in the 24-month-old group. Further assay of [3H]IP3 binding with cerebellar
      membranes showed significant reduction in Bmax values in the 15- and 24-month-old
      groups as compared to the 5-month-old group but Kd values were not changed. The
      decrease in mGluR1a receptor protein together with reduction in IP3R binding
      sites may play an important role in the decline in cerebellar functions with
      increasing age.

PMID- 9578138
TI  - Ascorbic acid stimulates DOPA synthesis and tyrosine hydroxylase gene expression
      in the human neuroblastoma cell line SK-N-SH.
AB  - Ascorbic acid is well known to induce noradrenaline synthesis in sympathetic
      nervous cells. In a series of experiments we found that incubation of the
      neuroblastoma cell line SK-N-SH with ascorbic acid (100-500 microM) for 2 h
      results in a significantly enhanced synthesis of 3,4-dihydroxyphenylalanine
      (DOPA) and dopamine. Additionally, cDNA-polymerase chain reaction (cDNA-PCR)
      analysis of relative mRNA levels corresponding to the enzymes involved in
      catecholamine synthesis revealed a 3-fold increase of tyrosine hydroxylase gene
      expression after 5 days of incubation with ascorbic acid (200 microM), whereas
      expression of dopamine-beta-hydroxylase was found to be unaltered. In summary the
      data give evidence that ascorbic acid leads to enhanced DOPA production in SK-N
      SH cells by two different mechanisms: at the metabolic level after short-term
      incubation and by increasing the tyrosine hydroxylase gene expression after long
      term incubation. Based on these data we suppose that enhancement of DOPA
      synthesis by ascorbic acid may be useful in the treatment of early Parkinson's
      disease.

PMID- 9578139
TI  - Cholecystokinin modulates the aversive component of morphine withdrawal syndrome
      in rats.
AB  - The conditioned place aversion paradigm was used to investigate the role of
      cholecystokinin in the aversive/dysphoric component of morphine abstinence.
      Several cholecystokinin ligands were chronically administered during the
      development of morphine dependence: the CCKA antagonist devazepide, the CCKB
      antagonists PD-134,308 and L-365,260, and the CCKB agonist BC 264. The CCK-B
      antagonists L-365,260 and PD-134,308 decreased and completely blocked
      (respectively) the place aversion induced by naloxone in morphine dependent
      animals whereas BC 264 and devazepide were inactive in this model. No effect was
      observed in non-dependent animals after chronic administration of these CCK
      ligands. These results show a distinct role for CCK receptors in the regulation
      of the motivational component of morphine abstinence, probably related to their
      differential effects in the regulation of limbic dopaminergic neurons.

PMID- 9578140
TI  - Mutant p53 may selectively suppress glial specific proteins in pluripotential
      human neuroectodermal tumor cells.
AB  - The p53 gene is mutated in pluripotential human neuroectodermal tumor DAOY cells
      which express both glial and neuronal markers. In most cells, nuclear m-p53
      immunostaining was intense while cytoplasmic glial specific proteins (GSPs) were
      present at low levels. Conversely, glial fibrillary acidic protein (GFAP) and
      glutamine synthetase (GS) were expressed in the few cells devoid of nuclear m-p53
      immunoreactivity. The level of neuron specific enolase (NSE) staining was low and
      not different between p53 positive and p53 negative cells. Therefore, a
      selective, mutually exclusive expression relationship exists between cytoplasmic
      GSPs and nuclear m-p53. Upon treatment with epidermal growth factor (EGF) and
      dibutyrylcyclic AMP, overall cytoplasmic GFAP and GS levels were increased while
      nuclear p53 was suppressed but a mutually exclusive expression pattern between
      these proteins was maintained. In cells which also express NSE, GFAP was
      selectively stimulated suggesting that nuclear expression of m-p53 and
      cytoplasmic expression of GSPs may be functionally related.

PMID- 9578141
TI  - Retrograde double-labeling study of retinal ganglion cells from the ipsilateral
      vLGN and SC in the albino rat.
AB  - Retinal ganglion cells with branches to the ipsilateral ventral lateral
      geniculate nucleus (vLGN) and superior colliculus (SC) were studied by retrograde
      fluorescent double-labeling. Double-labeled cells were found in the ventral
      temporal crescent of the retina, with a few ipsilaterally projecting single
      labeled cells scattered in this area. Single-labeled vLGN-projecting cells were
      found predominantly in the ventral-temporal crescent and to a lesser extent in
      the temporal and dorsotemporal octant. SC-projecting cells were present
      predominantly in the ventral-temporal crescent and to a lesser extent in the
      ventral and ventronasal octant. Our best animal model had 2200 ipsilaterally
      labeled cells. There were 451 (20.5%) double-labeled vLGN and SC-projecting
      cells, 561 (25.5%) single-labeled vLGN-projecting cells, and 1186 (53.9%) single
      labeled SC-projecting cells.

PMID- 9578142
TI  - Immunocytochemical localization of aquaporin 1 in the rat retina.
AB  - Aquaporins transport water through membranes of various tissues, thereby playing
      crucial roles in a number of physiological processes. Aquaporin 1 (AQP1, also
      known as CHIP, channel forming integral membrane protein of 28 kDa) is the first
      identified protein to function as a water channel and has been recently shown to
      be present in the rat retina. This study was conducted to examine the cellular
      localization of AQP1 in the rat retina by immunocytochemistry using antisera
      against AQP1. The AQP1-like immunoreactivity was present in a certain population
      of amacrine cells and in the proximal processes of Muller cells. Thus, AQP1
      appears to be important in the retinal homeostasis.

PMID- 9578143
TI  - Comparison of an adenosine A1 receptor agonist and antagonist on the rat EEG.
AB  - The effects of the selective adenosine A1 receptor agonist N6
      cyclopentyladenosine (CPA; 1 and 0.1 mg/kg, i.p.) and the A1 selective antagonist
      8-cyclopentyl-1,3-dipropylxanthine (CPX) have been examined on the
      electroencephalogram (EEG) of intact rats. From four EEG leads the EEG signal was
      subjected to Fast Fourier Transform and analysed both in narrow (0.01629638 Hz)
      and wide frequency bands. CPA tended to increase EEG power at low frequencies,
      and in several of the narrow frequency bands significantly shifted peak
      frequencies to lower values. The agonist also increased peak power in some
      frequency bands. The results are consistent with the view that A1 adenosine
      receptors mediate a generally depressant effect on neuronal activity in most
      brain regions, but may increase activity in areas with low resting rates of
      firing. The modest elevation of wave power by CPX indicates a limited control by
      resting endogenous adenosine, which is greatest in areas of highest activity,
      consistent with adenosine release being related to neuronal activity.

PMID- 9578144
TI  - Role of arachidonic acid metabolites in the action of a beta adrenergic agonist
      on human monocyte phagocytosis.
AB  - The mechanisms by which beta adrenergic stimulation regulates phagocytosis of
      Candida albicans by human peripheral monocytes (HPM) are characterized.
      Isoproterenol (ISO) inhibits phagocytosis in a concentration-dependent manner.
      This effect was blunted by propranolol, inhibitors of phospholipase A2 (PLA2),
      cyclooxygenase and verapamil, pointing to a participation of arachidonic acid
      (AA) metabolites and calcium in the phenomenon. Prostaglandin E2 (PGE2) and
      dibutyryl cyclic AMP (db-cAMP) also exerted the same inhibitory effect on
      phagocytosis. ISO interacts with beta adrenergic receptors of HPM increasing PGE2
      and cAMP. We conclude that the mechanisms by which beta adrenergic stimulation
      regulates phagocytosis of Candida albicans by HPM appear to be secondary to beta
      adrenoceptor-mediated hydrolysis of AA accompanied by an increase in PGE2
      generation and cAMP production. Both PGE2 and cAMP could act as mediators of the
      inhibitory action of beta agonists on the HPM-phagocytosis process.

PMID- 9578145
TI  - Eicosanoid secretion by human endothelial cells exposed to normal pregnancy and
      preeclampsia plasma in vitro.
AB  - Eicosanoids play an important role in the pathogenesis of preeclampsia. The major
      eicosanoid metabolite reported to be secreted by endothelial cells, the
      vasodilator prostacyclin, is generally reduced in preeclampsia. By contrast, it
      was shown previously that prostacyclin secretion by cultured human umbilical vein
      endothelial (HUVE) cells is increased significantly after exposure to blood from
      preeclamptic women. In the current study, eicosanoid profiles in conditioned
      media from HUVE cells incubated with pregnancy plasma were analyzed by high
      performance liquid chromatography, thin layer chromatography and quantitative
      radio- and enzyme immunoassays. More prostaglandin F2alpha, prostacyclin and 8
      isoprostane were secreted after exposure to plasma from preeclamptic women than
      plasma from matched, normal pregnant patients. Predominant secretion of the
      vasoconstrictor prostaglandin F2alpha by HUVE cell cultures and a stimulatory
      effect of preeclampsia plasma on eicosanoid biosynthesis underscore the
      importance of bioactive lipids in the vasospasm associated with clinical
      preeclampsia.

PMID- 9578146
TI  - Oxatomide inhibits synthesis and release of platelet-activating factor in human
      neutrophils.
AB  - Effect of oxatomide on release and production of platelet-activating factor (PAF)
      in neutrophils obtained from asthmatic and non-asthmatic patients was
      investigated. Neutrophils were preincubated with or without oxatomide and
      stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (f-MLP, 10 microM)
      for 15 min. PAF activity was detected by aggregation of washed guinea pig
      platelets. PAF activity released from asthmatic neutrophils without preincubation
      of oxatomide was 7.97[0.22] (mean[SEM], ng/10(7) cells) in supernatants and
      33.4[0.26] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M
      of oxatomide, PAF activity reduced to 6.77[0.37] (mean[SEM], ng/10(7) cells),
      3.99[0.25], and 0.96[0.05] (n = 15) in the supernatants, and 22.4[0.31],
      16.7[0.22], and 6.35[0.11] (n = 15) in the cell pellets, respectively. PAF
      activity in non-asthmatic neutrophils without preincubation of oxatomide was
      6.35[0.12] (mean[SEM], ng/10(7) cells) in supernatants and 27.9[0.25] in cell
      pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of oxatomide, PAF
      activity reduced to 5.02[0.16] (mean [SEM], ng/10(7) cells), 3.96[0.11], and
      0.94[0.03] (n = 10) in the supernatants, and 28.4[0.69], 13.78[0.17], and
      2.88[0.27] (n = 10) in the cell pellets, respectively. Our results showed that
      preincubation with oxatomide caused a dose-dependent inhibition of intra- and
      extracellular PAF activity from asthmatic and non-asthmatic neutrophils in the
      same manner.

PMID- 9578147
TI  - Inhibitory effect of amphotericin B on leukotriene B4 synthesis in human
      neutrophils in vitro.
AB  - Our objective was to determine the effect of amphotericin B on leukotriene (LT)
      A4 hydrolase in human neutrophil cytosol and to examine its effect on intact
      neutrophils in vitro. Cytosolic fractions were assayed for LTA4 hydrolase and 5
      lipoxygenase activity in the presence or absence of amphotericin B. The IC50 of
      amphotericin B for LTA4 hydrolase activity was 0.72 microM. No inhibition of 5
      lipoxygenase activity in the cytosolic fraction was detected. The IC50 of
      amphotericin B for leukotriene B4 synthesis in intact neutrophils was 0.43
      microM. The 5-hydro(per) oxy-eicosatetraenoic acid (5-H(P)ETE) synthesis was
      diminished in intact cells by 66.8 [3.4]% (mean[SEM]) in the presence of 0.01 mM
      amphotericin B. Thus, amphotericin B inhibited the synthesis of LTB4 and 5
      H(P)ETE in neutrophils in vitro. Differences between the results of studies on
      cytosol and on intact cells suggest that amphotericin B is involved in a complex
      interaction in the intact cell.

PMID- 9578149
TI  - Effect of vitamin D3 on interleukin-6 synthesis induced by prostaglandins in
      osteoblasts.
AB  - In previous studies, we have shown that prostaglandin F2alpha (PGF2alpha)
      stimulates interleukin-6 (IL-6) synthesis via activation of protein kinase C in
      osteoblast-like MC3T3-E1 cells, and that prostaglandin E1 (PGE1) induces the
      synthesis of IL-6 through protein kinase A activation. In the present study, we
      investigated the effect of vitamin D3 on IL-6 synthesis in MC3T3-E1 cells. 1,25
      Dihydroxyvitamin D3 (1,25-(OH)2D3), an active form of vitamin D3, inhibited the
      IL-6 synthesis induced by PGF2alpha or PGE1. On the contrary, 24,25
      dihydroxyvitamin D3, an inactive form of vitamin D3, had no effect. 1,25-(OH)2D3
      did not affect the IL-6 synthesis stimulated by 12-O-tetradecanoyl-phorbol-13
      acetate, an activator of protein kinase C. The IL-6 synthesis induced by cholera
      toxin or forskolin was significantly inhibited by 1,25-(OH)2D3. However, 1,25
      (OH)2D3 had little effect on the IL-6 synthesis induced by dibutyryl cAMP. These
      results strongly suggest that 1,25-(OH)2D3, an active form of vitamin D3,
      inhibits IL-6 synthesis at both the protein kinase C pathway and the protein
      kinase A pathway in osteoblasts.

PMID- 9578148
TI  - Prednisolone inhibits synthesis of 5-H(P)ETE in eosinophils from asthmatic
      patients during a wheezing attack but not during remission.
AB  - To estimate the effect of prednisolone on 5-lipoxygenase activity in eosinophils
      obtained from asthmatic patients, cytosolic levels of 5-H(P)ETE and Ca2+ were
      measured in the eosinophils which were exposed to prednisolone in vitro and in
      vivo. The mean level of 5-H(P)ETE during a wheezing attack was significantly
      lower in the patients who had received intravenous prednisolone (500 mg/day).
      Incubation with prednisolone in vitro caused a dose-dependent decrease in the
      cytosolic levels of 5-H(P)ETE and Ca2+ in eosinophils obtained during the
      wheezing attack, but not in the eosinophils obtained from during remission.
      Results suggest that prednisolone inhibits the level of 5-H(P)ETE in the
      eosinophil cytosols of asthmatic patients during a wheezing attack, probably by
      inhibition of 5-lipoxygenase activity which is involved in the reduction of the
      influx of Ca2+.

PMID- 9578150
TI  - High density lipoprotein fatty acids in dementia.
AB  - High density lipoproteins (HDL) are small plasma particles which may be able to
      pass through the blood-brain barrier. We have therefore studied the fatty acids
      of HDL in patients with dementia to determine whether the changes are consistent
      with those previously reported in brain tissue. The HDL phospholipid and the HDL
      cholesteryl ester both showed reduced concentrations of arachidonic acid (20:4n6)
      as compared to normal controls. HDL may be a useful plasma fraction for study of
      lipids in neurodegenerative diseases.

PMID- 9578151
TI  - Glomerular thromboxane contributes to pressor response in deoxycorticosterone
      acetate-salt hypertension.
AB  - To assess the role of renal thromboxane in a salt sensitive pressor response in
      hypertension, urinary excretion of thromboxane and its release from isolated
      glomeruli and renal papillae were examined in deoxycorticosterone acetate treated
      rats with normal (0.6%, n = 12) and high (4%, n = 12) salt diets for 8 weeks.
      Mean blood pressure, measured directly by an implanted aortic catheter, was
      higher in the high salt diet group than in the normal salt diet group (146 +/- 2
      vs 119 +/- 2 mmHg, P<0.01). Urinary excretion of thromboxane B2 and 6-keto
      prostaglandin F1alpha in the high salt group were significantly higher than those
      in the normal salt diet group, but there was no difference in urinary excretion
      of prostaglandin E2 between the two groups. Release of thromboxane B2, 6-keto
      prostaglandin F1alpha, and prostaglandin E2 from isolated glomeruli in the high
      salt diet group increased significantly by 104%, 55%, and 74%, respectively,
      compared with the normal salt diet group. Stepwise multiple linear regression
      analysis showed that significant contributory factors for mean blood pressure in
      deoxycorticosterone acetate treated rats were urinary excretion of sodium
      (F=14.187, P<0.01) and release of thromboxane B2 from isolated glomeruli
      (F=4.135, P<0.05). The unstandardized coefficient (R) calculated from the
      regression function using these two factors was 0.875 and R2 was 0.765. The
      manifest synthesis of thromboxane in renal glomeruli has an important role on
      salt sensitive pressor response in deoxycorticosterone acetate-salt hypertension
      of rats.

PMID- 9578152
TI  - Ethanol and parturition: a role for prostaglandins.
AB  - A common pattern of birth defects was reported in children born to alcoholic
      women over 20 years ago. Shortly thereafter the constellation of defects became
      known as the Fetal Alcohol Syndrome, and reports from around the world served to
      acknowledge the pervasiveness of the disorder. Simultaneously with the clinical
      reports, animal models were developed to characterize the full spectrum of the
      teratogenic effects of ethanol. Not only did these animal models serve to define
      the actions of ethanol on fetal growth and development at the molecular
      pharmacological, neuroanatomical, and behavioral level, but unintentionally, they
      have resulted in renewed scientific interest in the effects of ethanol on
      pregnancy and parturition itself. The purpose of this review is twofold. First we
      will consolidate and summarize data from both clinical and basic research that
      pertains to ethanol and parturition. These data will demonstrate that ethanol
      consumption during pregnancy results in both delayed as well as premature
      delivery depending upon the pattern of consumption and timing of exposure. With
      these data as a background, the second objective will be to present a theoretical
      case for prostaglandins as possible mediators of ethanol-induced effects on the
      onset of parturition.

PMID- 9578153
TI  - Effects of daphnodorin A, B and C, new flavans isolated from traditional Chinese
      medicine, on the 12-lipoxygenase and cyclooxygenase metabolism of arachidonic
      acid in rabbit platelets.
AB  - The effects of daphnodorin A, B and C, isolated from the root and bark of Daphne
      odora THUNB, on the activities of 12-lipoxygenase and cyclooxygenase in rabbit
      platelets were examined. Daphnodorin A and C were inhibitors of platelet 12
      lipoxygenase and cyclooxygenase activities. Daphnodorin B had no effect on the
      two enzymatic pathways. The present data raise the possibility that daphnodorin A
      and C can be anti-thrombotic and anti-atherosclerotic drugs through the
      suppressive influence on the platelet 12-lipoxygenase and cyclooxygenase.

PMID- 9578154
TI  - Activators of protein kinase A decrease the levels of free arachidonic acid in
      osteoblasts via stimulation of phosphatidylcholine and phosphatidylethanolamine
      synthesis.
AB  - In order to examine the role of protein kinase A (PKA) in the regulation of
      arachidonic acid availability, the interaction between cAMP agonists and the G
      protein activator AIF4- in their effects on phospholipid metabolism were measured
      in MC3T3-E1 osteoblasts. We show that forskolin and 8-brcAMP, activators of PKA,
      amplify the AIF4(-)-induced stimulation of phosphatidylinositol-specific
      phospholipase C (phosphatidylinositol inositolphosphohydrolase; EC 3.1.4.3),
      measured by the formation of [3H]inositol phosphates in prelabeled cells.
      However, the AIF4(-)-stimulated production of 1,2-diacylglycerols and the release
      of [3H]arachidonic acid ([3H]AA) were inhibited 50-75% by forskolin and 8
      bromocAMP. Furthermore, pretreatment with PKA activators prevented much of the
      AIF4(-)-induced loss of [3H]AA from phosphatidylcholine and
      phosphatidylethanolamine in prelabeled osteoblasts. In addition, in the absence
      of AIF4-, forskolin was found to stimulate the incorporation of [3H]AA and
      [32P]orthophosphoric acid selectively into these two major phospholipids and
      selectively increased their mass. The effects of forskolin and 8-BrcAMP on the
      levels of free [3H]AA were completely reversed by pretreatment with the PKA
      inhibitor H-89. Therefore, our findings suggest that the activation of cAMP
      dependent protein kinase can reduce the availability of free arachidonic acid for
      prostaglandin synthesis in osteoblast cells by stimulating its reesterification
      via phospholipid resynthesis.

PMID- 9578155
TI  - Arginine vasopressin stimulates phospholipid methylation in cultured rat
      mesangial cells: possible role for PGE2 production.
AB  - Incorporation of [3H-methyl] groups into phospholipids and prostaglandin E2
      (PGE2) production in cultured rat mesangial cells were examined in the presence
      and absence of arginine vasopressin (AVP). In cells stimulated with AVP, a rapid
      increase in the incorporation of [3H-methyl] group into phospholipids was
      observed within 1 min after stimulation. The [3H-methyl] group present in the
      phospholipids began to decline 2.5 min after stimulation. The production of PGE2
      increased with AVP treatment, and the decline in methylated phospholipids
      paralleled the release of PGE2 in AVP-stimulated cells. The inhibition of
      phospholipid methylation by treatment with adenosyl-S-isobutyl mercaptan (SIBA)
      resulted in a marked decrease in AVP-stimulated PGE2 production. In order to
      determine the identity of the methylated phospholipids, [3H-methyl] incorporation
      into phosphatidylethanolamine derivatives was examined. In AVP-stimulated cells,
      an increase of [3H-methyl] labeled phosphatidylcholine and
      lysophosphatidylcholine was observed after stimulation with AVP, followed by an
      apparent increase of [3H-methyl] labeled lysophosphatidylcholine. These findings
      indicate that AVP stimulates phospholipid methylation in cultured rat mesangial
      cells and phosphatidylcholine, synthesized by a transmethylation pathway, may be
      a source for PGE2 production.

PMID- 9578156
TI  - The renaissance of antibody therapy.

PMID- 9578157
TI  - Prophylaxis in orthopaedic implant surgery--should we use a glycopeptide?

PMID- 9578158
TI  - Alternatives to vancomycin in treating methicillin-resistant Staphylococcus
      aureus infections.

PMID- 9578160
TI  - Antibacterial efficacy of nisin against multidrug-resistant Gram-positive
      pathogens.
AB  - The rapid spread of multidrug-resistant bacterial pathogens necessitates the
      search for alternative antibacterial agents. We examined the efficacy of the
      antibiotic nisin against 56 multidrug-resistant isolates of Streptococcus
      pneumoniae, 33 Staphylococcus aureus and 29 vancomycin-resistant Enterococcus
      faecium and Enterococcus faecalis isolates. The test strains represented a large
      variety of clonal types (as determined by a combination of DNA fingerprints)
      isolated from a variety of geographic sources, and included some of the major
      internationally-spread multiresistant epidemic clones of S. pneumoniae and
      methicillin-resistant S. aureus (MRSA), MRSA strains resistant to over 16
      generically distinct antibacterial agents, and enterococcal strains resistant to
      all currently available chemotherapeutic agents including glycopeptides. In the
      overwhelming majority of cases, treatment of growing cultures with nisin at 1
      mg/L (S. pneumoniae) or 10-20 mg/L (in MRSA and enterococci) caused extensive
      (10(3)- to 10(4)-fold) loss of viable titre accompanied by various degrees of
      loss in the optical density of the cultures, which was most extensive in
      pneumococci (>90%) and least extensive (40-50%) in enterococci. Nevertheless,
      extensive variation in rates of nisin-induced autolysis was observed in each
      bacterial species. Serial exposure of a penicillin-susceptible strain of S.
      pneumoniae to nisin (1 mg/L) in liquid culture resulted in the rapid appearance
      of stable nisin-resistant mutants in which the MIC increased from 0.4 to 6.4 mg/L
      and the resistance trait was transferable by genetic transformation.

PMID- 9578159
TI  - Antimicrobial prophylaxis in orthopaedic surgery: the role of teicoplanin.
AB  - Orthopaedic joint replacement is generally considered 'clean' surgery
      characterized by a low incidence of infection. In recent years the use of a clean
      theatre environment, high local concentrations of antibiotic in the cement and
      systemic antibiotic prophylaxis have been recognized as important measures to
      reduce infection rates significantly, and this has been supported by clinical
      trials. Staphylococcus aureus and Staphylococcus epidermidis cause at least half
      of all orthopaedic surgical infections. Gram-negative bacilli are involved to a
      much lesser extent (10-30%). First- and second-generation cephalosporins are
      currently considered by most authors as standard prophylaxis in elective
      orthopaedic surgery. In the light of the increasing incidence of methicillin
      resistance in coagulase-positive and -negative staphylococci, it is becoming more
      important for antibiotics to act efficiently against such organisms if they are
      to be of value in prophylaxis in orthopaedic surgery. A combined, single-dose of
      vancomycin/gentamicin has been used successfully in an open, controlled study in
      patients undergoing total joint arthroplasty but, given the disadvantages
      associated with the use of vancomycin, teicoplanin may be an alternative choice
      in such procedures. This review analyses four comparative trials of the efficacy
      and safety of teicoplanin, two with cefamandole, one with cefuroxime and one with
      cephazolin, as prophylaxis in orthopaedic total joint replacement surgery.

PMID- 9578161
TI  - In-vitro activity and killing effect of quinupristin/dalfopristin (RP59500) on
      nosocomial Staphylococcus aureus and interactions with rifampicin and
      ciprofloxacin against methicillin-resistant isolates.
AB  - Quinupristin/dalfopristin (RP59500) is a novel streptogramin and a semisynthetic
      derivative of pristinamycins IA and IIB. The following properties of RP59500 were
      investigated: (i) its in-vitro activity against 164 hospital isolates of
      Staphylococcus aureus, 101 of which were methicillin-resistant (MRSA); (ii) its
      killing effect against 24 MRSA and seven methicillin-susceptible (MSSA) isolates;
      (iii) its interactions with rifampicin and ciprofloxacin against 18 MRSA
      isolates, six susceptible to both rifampicin and ciprofloxacin and 12 resistant
      to both, at 1 x MIC, 2 x MIC and 4 x MIC. Rifampicin and ciprofloxacin were
      applied at a concentration equal to their mean serum levels in order to establish
      the clinical relevance of the results. The MIC50, MIC90, MBC50 and MBC90 of
      quinupristin/dalfopristin were, respectively, < or = 0.015, 2, 0.12 and 2 mg/L
      for MRSA isolates and < or = 0.015, 0.06, < or = 0.015 and 0.25 mg/L for MSSA
      isolates. All isolates were inhibited by quinupristin/dalfopristin. Its killing
      effect varied with concentration and time, being optimal at 4 x MIC and after 24
      h growth. Strains surviving 24 h exposure to this agent had much higher MICs than
      the parent strain, but only a limited number of them became resistant.
      Quinupristin/dalfopristin at 2 x MIC and 4 x MIC showed in-vitro synergy with
      rifampicin against highly resistant isolates mainly at 6 h and 24 h of growth
      involving 50-83% of MRSA isolates, and showed synergy with ciprofloxacin at 24 h
      involving 42-75% of isolates. The MIC increase in colonies surviving at 24 h was
      restricted by the presence of rifampicin or ciprofloxacin. In contrast, the above
      combinations acted synergically over the total number of MRSA strains susceptible
      to both rifampicin and ciprofloxacin. The above findings show that
      quinupristin/dalfopristin is a very potent antistaphylococcal agent, and that its
      activity against MRSA isolates is enhanced when it is combined with rifampicin or
      ciprofloxacin.

PMID- 9578162
TI  - The effect of antifungal drugs in combination on the growth of Candida glabrata
      in solid and liquid media.
AB  - The effect of drugs in combination on the growth of Candida glabrata was studied
      in solid medium by demonstration of reduced or enhanced growth, and in liquid
      medium by determination of interaction indices. Amphotericin B and 5
      fluorocytosine showed a synergic effect, while combinations of amphotericin B and
      miconazole, and miconazole and 5-fluorocytosine exhibited antagonistic effects.
      In addition, concentration-dependent antagonism was observed amongst combinations
      of metabolic inhibitors, between inhibitors of sterol biosynthesis (terbinafine,
      miconazole, ketoconazole, clotrimazole, econazole, fluconazole, itraconazole and
      amorolfine) and inhibitors of nucleic acid or protein biosynthesis (5
      fluorocytosine, 5-fluorouracil, rifampicin and chlortetracycline). This
      antagonism was strain-specific, occurring with C. glabrata strain 4,
      Saccharomyces cerevisiae strain 237 and Candida albicans strain 72R, but not with
      C. albicans strain 6406 or Candida parapsilosis strain 3104.

PMID- 9578163
TI  - Cefepime and amikacin synergy in vitro and in vivo against a ceftazidime
      resistant strain of Enterobacter cloacae.
AB  - The activities of cefepime and amikacin alone or in combination against an
      isogenic pair of Enterobacter cloacae strains (wild type and stably derepressed,
      ceftazidime-resistant mutant) were compared using an experimental model of
      pneumonia in non-leucopenic rats. Animals were infected by administering 8.4
      log10 cfu of E. cloacae intratracheally, and therapy was initiated 12 h later. At
      that time, the animals' lungs showed bilateral pneumonia and contained more than
      7 log10 E. cloacae cfu/g tissue. Because rats eliminate amikacin and cefepime
      much more rapidly than humans, renal impairment was induced in all animals to
      simulate the pharmacokinetic parameters of humans. In-vitro susceptibilities
      showed an inoculum effect with cefepime proportional to the bacterial titre
      against the two strains, but more pronounced with the stably derepressed mutant
      strain, whereas with bacterial concentrations of up to 7 log10 cfu/mL, no
      inoculum effect was observed with amikacin. In-vitro killing indicated that
      antibiotic combinations were synergic only at intermediate concentrations. At
      peak concentrations, the combination was merely as effective as amikacin alone.
      At trough concentrations, a non-significant trend towards the superiority of the
      combination over each antibiotic alone was noted. Moreover, cefepime was either
      bacteriostatic or permitted regrowth of the organisms in the range of antibiotic
      concentrations tested. Although each antibiotic alone failed to decrease
      bacterial counts in the lungs, regardless of the susceptibility of the strain
      used, the combination of both antibiotics was synergic and induced a significant
      decrease in the lung bacterial count 24 h after starting therapy when compared
      with tissue bacterial numbers in untreated animals or animals treated with either
      antibiotic alone. No resistant clones emerged during treatment with any of the
      antibiotic regimens studied.

PMID- 9578164
TI  - Nosocomial breakthrough fungaemia during antifungal prophylaxis or empirical
      antifungal therapy in 41 cancer patients receiving antineoplastic chemotherapy:
      analysis of aetiology risk factors and outcome.
AB  - Forty-one episodes of breakthrough fungaemia occurring over a 7.5 year period in
      the National and St Elizabeth's Cancer Institutes in Bratislava, Slovakia, were
      analysed. Five of them occurred during prophylaxis with fluconazole (one
      Torulopsis glabrata, one Hansenula anomala, two Candida krusei and one Candida
      parapsilosis), ten with itraconazole (three Trichosporon pullulans, one
      Trichosporon beigelii, one Cryptococcus laurentii, three Candida albicans and two
      T. glabrata), 11 during prophylaxis with ketoconazole (one Candida norvegenesis,
      one C. parapsilosis, one C. krusei, one Candida tropicalis, five C. albicans, one
      Candida stellatoidea and one C. laurentii and 15 during empirical therapy with
      amphotericin B (ten C. albicans, two T. beigelii and three Candida lusitaniae).
      The most frequent risk factors for breakthrough fungaemia were neutropenia,
      previous therapy with multiple antibiotics and recent catheter insertion.
      Comparing these episodes with 38 non-breakthrough fungaemias (appearing at the
      same institute in the same period) differences in certain risk factors were
      noted: breakthrough fungaemias were more frequently observed in patients with
      acute leukaemia (39.0% vs 5.2%, P < 0.001), mucositis (34.2% vs 13.1%, P < 0.05),
      prophylaxis with quinolones (58.5% vs 15.8%, P < 0.0001) and catheter-associated
      infections (29.3% vs 2.6%, P < 0.003). In this subgroup overall mortality (36.6%
      vs 28.8%) or early attributable mortality (22.0% vs 23.6%) were not significantly
      different.

PMID- 9578165
TI  - In-vitro activity of 21 beta-lactam antibiotics against penicillin-susceptible
      and penicillin-resistant Streptococcus pneumoniae.
AB  - MICs of 21 beta-lactams were determined by agar dilution against 283 penicillin
      susceptible (pen-S), 122 intermediate (pen-I) and 23 fully penicillin-resistant
      (pen-R) pneumococci. MICs of all beta-lactams increased with increasing MICs of
      penicillin. Clometocillin was the most active penicillin against pen-I or pen-R
      pneumococci. All oral cephalosporins except cefuroxime and cefpodoxime were less
      active than penicillin and none was satisfactory against pen-I or pen-R
      pneumococci. The parenteral third- and fourth-generation cephalosporins (except
      ceftazidime) were similar in activity to penicillin against pen-S isolates.
      Cefpirome showed the lowest mean MICs against pen-I and pen-R strains.

PMID- 9578166
TI  - Anti-anaerobic activity of erythromycin, azithromycin and clarithromycin: effect
      of pH adjustment of media to compensate for pH shift caused by incubation in CO2.
AB  - The activity of erythromycin, azithromycin and clarithromycin against 112
      anaerobes was tested by the Oxyrase agar dilution MIC method at pH 7.2 without
      supplemental CO2 and by an agar dilution MIC method in CO2 with media adjusted to
      pH 8.0. MICs (mg/L) of erythromycin, azithromycin and clarithomycin against
      Bacteroides fragilis ATCC 25285 and Bacteroides thetaiotaomicron ATCC 29741 were
      similar by the two methods. MICs for 94 clinical isolates tested by the two
      methods were within two dilutions of each other. Eighteen additional isolates
      required CO2, and did not grow in Oxyrase. With the exception of fusobacteria,
      with which azithromycin yielded the lowest MICs, clarithromycin had the lowest
      MICs with both methods. These results show that the pH effect of incubation in
      CO2 can be avoided by using the Oxyrase method, or by incubating in CO2 with pH
      adjusted to 8.0. The latter method has the advantage of allowing testing of
      strains requiring CO2.

PMID- 9578167
TI  - Trovafloxacin compared with levofloxacin, ofloxacin, ciprofloxacin, azithromycin
      and clarithromycin against unusual aerobic and anaerobic human and animal bite
      wound pathogens.
AB  - The activity of trovafloxacin and five other oral agents against 250 aerobic and
      137 anaerobic strains isolated from human and animal bite wounds was determined
      by an agar dilution method. Trovafloxacin was active against all aerobic and
      fastidious facultative isolates at < or = 0.5 mg/L and all anaerobes at < or = 2
      mg/L (Bacteroides tectum, Porphyromonas salivosa and Prevotella heparinolytica, <
      or = 0.25 mg/L; Porphyromonas spp., < or = 0.5 mg/L; Prevotella spp. and
      peptostreptococci, < or = 2.0 mg/L), except Fusobacterium nucleatum and other
      fusobacteria (MIC90 < or = 4 mg/L). Levofloxacin was generally one to two
      dilutions more active than ofloxacin, while ciprofloxacin was active against
      aerobes (MIC < or = 1 mg/L) but less active against anaerobic strains (MIC90 < or
      = 16 mg/L).

PMID- 9578168
TI  - Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B
      against Cryptococcus neoformans.
AB  - The activity of fluconazole and amphotericin B against three isolates of
      Cryptococcus neoformans was evaluated, with fluconazole and amphotericin B MICs
      of 2.0-4.0 mg/L and 1.0 mg/L respectively, using time-kill curve methods.
      Fluconazole was fungistatic against all isolates tested (<99.9% decrease in cfu
      from initial inoculum). The fungistatic activity of fluconazole was not enhanced
      by increasing the concentration of antifungal in solution. In contrast,
      amphotericin B was markedly fungicidal (> or = 99.9% decrease in cfu from initial
      inoculum). Both the rate and the extent of amphotericin B activity were enhanced
      when drug concentration was increased.

PMID- 9578169
TI  - Comparative therapeutic efficacy of clinafloxacin in a Pseudomonas aeruginosa
      mouse renal abscess model.
AB  - A deep-seated Pseudomonas aeruginosa mouse kidney abscess model was used to
      compare the therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical
      trials, with that of clinically relevant standard drugs. Following 50 mg/kg oral
      doses, twice daily for five consecutive days, clinafloxacin produced a 4 log
      decrease in mean bacterial count, the greatest decrease of all drugs tested. The
      same dosage regimen resulted in complete bacterial eradication in 88% of the
      kidneys. No other compound produced total bacterial clearance in 50% of the
      kidneys at the highest dose tested.

PMID- 9578170
TI  - Treatment of Pseudomonas aeruginosa lung infection in cystic fibrosis with high
      or conventional doses of ceftazidime.
AB  - In cystic fibrosis patients with Pseudomonas aeruginosa colonization and
      increasing pulmonary infection, ceftazidime 150 mg/kg/day was compared with 320
      mg/kg/day. Changes in clinical findings, laboratory tests, pulmonary function and
      chest radiographs were evaluated after 14 days of treatment in hospital. Both
      treatments were associated with a significant improvement, but the higher dose
      did not offer an additional benefit. An increase in alanine aminotransferase
      (ALT) occurred after both treatments; with a significantly greater increase after
      the high-dose therapy (mean increase +/- S.E.M. 8% +/- 2% vs 2% +/- 1 %; P <
      0.01). All but one of the ALT values after treatment were within normal limits.

PMID- 9578172
TI  - Ampicillin-aminoglycoside interaction studies using Listeria monocytogenes.

PMID- 9578171
TI  - Antimicrobial susceptibility of community-acquired lower respiratory tract
      bacterial pathogens isolated in the UK during the 1995-1996 cold season.
AB  - The antimicrobial susceptibility of 1078 isolates of Haemophilus influenzae, 348
      Streptococcus pneumoniae and 258 Moraxella catarrhalis was determined. Overall
      15.1% of H. influenzae produced beta-lactamase; 98.8% were susceptible to co
      amoxiclav, 85.8% to cefaclor, 96% to clarithromycin and 100% to ciprofloxacin.
      The majority (94.2%) of M. catarrhalis produced beta-lactamase. The overall
      prevalence of low-level penicillin resistance (MIC = 0.12-1 mg/L) amongst
      isolates of S. pneumoniae was 3.4% and that of high-level resistance (MIC > or =
      2 mg/L) was 3.7%. Most (96.3%) of the isolates of S. pneumoniae were susceptible
      to amoxycillin (MIC < or = 0.5 mg/L), 96% to cefaclor (MIC < or = 8 mg/L), 90.7%
      to clarithromycin (MIC < or = 0.25 mg/L) and 89% to ciprofloxacin (MIC < or = 1
      mg/L).

PMID- 9578173
TI  - Serotyping of quinolone-resistant Neisseria gonorrhoeae isolates with alterations
      in GyrA and ParC.

PMID- 9578174
TI  - Increased incidence of ciprofloxacin resistance in penicillin-resistant
      pneumococci in Northern Ireland.

PMID- 9578175
TI  - Increase in the incidence of multidrug-resistant salmonellae in Ethiopia.

PMID- 9578176
TI  - Fluconazole penetration into the prostatic fluid of patients with AIDS-associated
      cryptococcal meningitis.

PMID- 9578177
TI  - An open, non-comparative evaluation of the efficacy and safety of amphotericin B
      lipid complex as treatment of neutropenic patients with presumed or confirmed
      pulmonary fungal infections.

PMID- 9578178
TI  - Do we still need dipyridamole?
AB  - There is limited evidence that dipyridamole is generally an effective
      antithrombotic agent when used alone, nor is there convincing evidence that the
      combination of aspirin and dipyridamole is more effective than aspirin alone,
      except perhaps in cerebrovascular disease. There is no consistent evidence to
      support the routine use of dipyridamole after coronary artery bypass grafting and
      in patients with occlusive peripheral vascular disease, although these remain
      common reasons for its use. Dipyridamole is a useful agent in 'pharmacological
      stress' testing in nuclear cardiology imaging and may be valuable when combined
      with warfarin in certain patient groups, such as those with prosthetic heart
      valves. When combined with aspirin, dipyridamole may be of value in the secondary
      prophylaxis of cerebrovascular disease, although further studies are clearly
      needed. In a significant proportion of cases, evidence-based medicine cannot
      support the current widespread continued prescription of dipyridamole in
      cardiological practice, but the jury is still out on cerebrovascular disease.

PMID- 9578179
TI  - Endocrine and adrenergic pharmacological intervention in diseases of the
      prostate.

PMID- 9578180
TI  - Postgraduate education in clinical pharmacology and therapeutics.

PMID- 9578181
TI  - Artemisinin population pharmacokinetics in children and adults with uncomplicated
      falciparum malaria.
AB  - AIMS: To investigate the pharmacokinetics of the antimalarial artemisinin in the
      field setting using sparsely collected data. METHODS: Artemisinin concentrations
      were determined by h.p.l.c. in a total of 107 capillary plasma samples collected
      on the first day and in 33 samples on the last day of a 5-day oral artemisinin
      regimen of 10 mg kg(-1) day(-1) in 23 paediatric (aged 2-12 years) and 31 adult
      (aged 16-45 years) Vietnamese patients with uncomplicated falciparum malaria. The
      population model was developed using NONMEM, incorporating interoccasion
      variability and accounting for a systematic change in artemisinin
      pharmacokinetics with time, modelled as a change in oral bioavailability.
      RESULTS: Clinical efficacy, in terms of parasite clearance and fever subsidence
      times, was comparable between children and adults. A one-compartment model with
      separate pharmacokinetic estimates for children and adults was found best to
      describe the disposition of artemisinin after oral administration. The population
      estimates for artemisinin clearance and distribution volume, respectively, were
      432 1 h(-1) and 16001 for adults and 14.41 h(-1) kg(-1) and 37.91 kg(-1) for
      children, with an intersubject variability (collectively for both age groups) of
      45% and 104%, respectively. The oral bioavailability was estimated to decrease
      from Day 1 to Day 5 by a factor of 6.9, a value found to be similar for children
      and adults. CONCLUSIONS: Artemisinin pharmacokinetic data was successfully
      derived in both paediatric and adult patients using 2-3 capillary blood samples
      taken in conjunction with parasitaemia monitoring. This study's findings
      advocated the dosing of artemisinin to children according to bodyweight and to
      adults according to a standard dose.

PMID- 9578182
TI  - Grapefruit juice enhances the bioavailability of the HIV protease inhibitor
      saquinavir in man.
AB  - AIMS: Saquinavir is a potent HIV protease inhibitor whose effectiveness is
      limited in vivo by its low bioavailability. Since saquinavir is metabolized by
      CYP3A4, the effect of grapefruit juice, an inhibitor of CYP3A4, was investigated
      on its bioavailability. METHODS: After an overnight fast, eight healthy
      volunteers were treated with either 400 ml grapefruit juice or water before
      intravenous (12 mg) or oral saquinavir (600 mg) was administered. Serial blood
      samples were obtained over the following 24 h and standardized meals were served
      5 and 10 h after the administration of saquinavir. The plasma concentrations of
      saquinavir were determined by high-performance liquid chromatography and
      pharmacokinetic parameters were calculated by routine methods. RESULTS: The AUC
      was not affected by grapefruit juice after intravenous administration, but it
      increased significantly from 76+/-96 (water, mean (s.d.) to 114+/-70 (microg l[
      1] h) (grapefruit juice) after oral saquinavir. Similarly, the oral
      bioavailability of saquinavir increased by a factor of 2 with grapefruit juice
      (from 0.7% to 1.4%). In contrast, clearance, volume of distribution and
      elimination half-life of saquinavir were not affected by grapefruit juice. After
      oral, but not after intravenous administration, the plasma concentration-time
      curve showed a second peak after lunch irrespective of pretreatment, suggesting
      enhancement of absorption by food. CONCLUSIONS: The studies demonstrate that
      grapefruit juice increases the bioavailability of saquinavir without affecting
      its clearance, suggesting that inhibition of intestinal CYP3A4 may contribute.
      Since the antiretroviral effect of saquinavir is dose-dependent, inhibition of
      CYP3A4 may represent a way to enhance its effectiveness without increasing the
      dose.

PMID- 9578183
TI  - Inhibitory effects of antiarrhythmic drugs on phenacetin O-deethylation catalysed
      by human CYP1A2.
AB  - AIMS: The aim of the study was to clarify whether the pharmacokinetic interaction
      between theophylline and mexiletine is mediated by inhibition of CYP1A2 and to
      assess the possible interaction potential of other antiarrhythmic drugs with
      drugs metabolized by CYP1A2. METHODS: The inhibitory effects of mexiletine and 10
      antiarrhythmic drugs on phenacetin O-deethylation, a marker reaction of CYP1A2,
      were studied using human liver microsomes and cDNA-expressed CYP1A2. RESULTS:
      Propafenone and mexiletine inhibited phenacetin O-deethylation with IC50 values
      of 29 and 37 microM, respectively. Disopyramide, procainamide and pilsicainide
      produced negligible inhibition of phenacetin O-deethylation (IC50 >1 mM).
      Amiodarone, bepridil, aprindine, lignocaine, flecainide and quinidine inhibited
      phenacetin O-deethylation in a concentration-dependent manner, although the
      inhibitory effects were relatively weak with IC50 values ranging from 86 to 704
      microM. Propafenone and mexiletine selectively abolished the high-affinity
      component of phenacetin O-deethylation in human liver microsomes. In addition,
      propafenone and mexiletine inhibited phenacetin O-deethylation catalysed by cDNA
      expressed CYP1A2. CONCLUSIONS: These data suggest that, among the antiarrhythmic
      drugs studied, propafenone and mexiletine are relatively potent inhibitors of
      CYP1A2, which may cause a drug-drug interaction with drugs metabolized by CYP1A2.

PMID- 9578184
TI  - Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors,
      omeprazole, lansoprazole, and pantoprazole.
AB  - AIMS: To study the pharmacokinetics of three proton pump inhibitors, omeprazole,
      lansoprazole, and pantoprazole, as well as any potential influence on CYP1A2
      activity (measured by means of rate of caffeine metabolism) of these compounds at
      single dose and repeated dose administration. METHODS: Fourteen healthy males,
      classified as 12 extensive metabolizers (EMs) and two poor metabolizers (PMs)
      according to the urinary S/R mephenytoin ratio, completed this open, randomized,
      three-way cross-over study. In each of the three 7-day treatment periods either
      omeprazole (20 mg), lansoprazole (30 mg) or pantoprazole (40 mg) in
      therapeutically recommended doses was administered once daily, and the
      pharmacokinetics of the proton pump inhibitors as well as the rate of caffeine
      metabolism was measured on days 1 and 7. RESULTS: In the EMs there was an
      increase in AUC from day 1 to day 7 for omeprazole. In the PMs the AUC of both
      omeprazole and lansoprazole was unchanged during repeated dosing, while for
      pantoprazole there was a tendency to a slight decrease. The AUC at steady state
      was for all three proton pump inhibitors 5 fold higher in PMs compared with EMs,
      indicating that the same proportion of the dose, irrespective of compound, is
      metabolized by CYP2C19. No induction of CYP1A2 was evident for any of the
      compounds in either EMs or PMs. CONCLUSIONS: The approximately 5 fold difference
      in AUC between EMs and PMs indicates that approximately 80% of the dose for all
      three proton pump inhibitors is metabolized by the polymorphically expressed
      CYP2C19. None of the three proton pump inhibitors, administered in
      therapeutically recommended doses, is an inducer of CYP1A2--neither in PMs nor in
      EMs.

PMID- 9578185
TI  - Single dose and steady state pharmacokinetics and pharmacodynamics of the ACE
      inhibitor imidapril in hypertensive patients.
AB  - AIMS: To investigate the pharmacokinetic profile of the ACE-inhibitor imidapril
      in 10 hypertensive patients after a first single dose (10 mg) and after 28 days
      therapy with imidapril 10 mg once daily. METHODS: Cmax, tmax, t1/2 and AUC of
      imidapril and imidaprilat were obtained. ACE-activity and arterial blood pressure
      during imidapril were corrected by a preceding placebo-investigation. RESULTS:
      The AUC of imidapril was 140 (43 s.d.) ng ml(-1) h after the first dose and 123
      (34 s.d.) ng ml(-1) h at steady state. AUC of the active moiety imidaprilat
      averaged 211 (101 s.d.) ng ml(-1) h after the first dose and 240 (55 s.d.) ng ml(
      1) h at the steady state investigation. Maximal ACE-inhibition was 75% after the
      single dose as well as at steady state. ACE inhibition before drug intake at day
      28 (i.e. trough) was 50%. The (placebo-corrected) maximal drop in diastolic blood
      pressure after imidapril was 22 mm Hg after the first dose and 25 mmHg at steady
      state. Exploratory analysis of imidaprilat plasma concentration vs effect
      profiles suggests a hyperbolic concentration effect relationship where data of
      the single dose contribute to the ascending part of an Emax-curve, whereas the
      plateau around Emax is maintained at steady state. CONCLUSIONS: In this group of
      hypertensive patients, the pharmacokinetic profile and the drop in ACE-activity
      as well as in blood pressure seen after a single dose of imidapril and at steady
      state were similar. The initial response to a test dose might therefore predict
      the response during chronic dosing.

PMID- 9578186
TI  - Concentrations and effects of buspirone are considerably reduced by rifampicin.
AB  - AIMS: The effects of rifampicin on the pharmacokinetics and pharmacodynamics of
      buspirone, a non-benzodiazepine anxiolytic agent, were investigated. METHODS: In
      a randomized, placebo-controlled cross-over study with two phases, 10 young
      healthy volunteers took either 600 mg rifampicin or matched placebo once daily
      for 5 days. On day 6, 30 mg buspirone was administered orally. Plasma buspirone
      concentrations and effects of buspirone were measured up to 10 h. RESULTS: The
      total area under the plasma buspirone concentration-time curve after rifampicin
      was 10.4% (95% CI, 6.3-14.5%) of that after placebo (1.64+/-0.35 ng ml(-1) h vs
      22.0+/-15.1 ng ml(-1) h (mean+/-s.d.); P< 0.01). Rifampicin decreased the peak
      plasma concentration of buspirone from 6.6+/-3.7 ng ml(-1) to 0.84+/-0.23 ng ml(
      1) (P< 0.01) and the half-life from 2.8+/-0.7 h to 1.3+/-0.5 h (P< 0.01). A
      significant (P<0.05) reduction in the effects of buspirone was observed in three
      of the six psychomotor tests employed (postural sway test with eyes closed,
      subjective drowsiness and overall drug effect) after rifampicin pretreatment.
      CONCLUSIONS: The strong interaction between rifampicin and buspirone is probably
      mostly due to enhanced CYP3A4-mediated first-pass metabolism of buspirone.
      Buspirone will most likely show a greatly reduced anxiolytic effect when used
      together with rifampicin or other potent inducers of CYP3A4 such as phenytoin and
      carbamazepine.

PMID- 9578188
TI  - Indicators for drug and therapeutics committees.
AB  - AIMS: This study describes development and field testing of a set of indicators
      for drug and therapeutics committees (DTCs) in hospitals. It was intended that
      these indicators should be accessible, useful and relevant in the Australian
      setting. METHODS: Candidate indicators were written following consultation and
      data collection. A framework of outcome, impact and process indicators was based
      on DTC goals, objectives and strategies. The candidate indicators were field
      tested over a 2 month period in teaching, city non-teaching, rural and private
      hospitals. The field tests provided response data for each indicator and
      evaluation of the indicators against criteria for accessibility, relevance,
      usefulness, clarity and resource utilisation. Consensus on which indicators to
      accept, modify or reject was reached at a workshop of stakeholders and experts,
      taking account of the field test results. RESULTS: Thirty-five candidate
      indicators were tested in 16 hospitals. Twenty-two had a response from >80% of
      sites, 23 had a mean relevance rating >3.5, 19 had a mean usefulness rating >3.5,
      27 were correctly interpreted by > 90% of sites and 25 could be collected in an
      acceptable time. The most acceptable indicators required least data collection or
      provided data deemed useful for purposes other than the field test. At the
      consensus workshop 13 indicators were accepted with no or minor change, nine were
      accepted after major modification and eight were discarded. It was recommended
      that a further five indicators should be merged or subsumed into one indicator.
      CONCLUSIONS: This study has developed and field tested a set of indicators for
      DTCs in Australia. The indicators have been taken up enthusiastically as a first
      attempt to monitor DTC performance but require ongoing validation and development
      to ensure continuing relevance and usefulness.

PMID- 9578187
TI  - Effect of selective phosphodiesterase 3 inhibition on the early and late
      asthmatic responses to inhaled allergen.
AB  - AIMS: Phosphodiesterase isoenzymes may play an important role in the regulation
      of airway calibre and bronchial smooth muscle function. Immunomodulatory actions
      may also be important in allergic airway inflammation. We have examined the
      effect of a phosphodiesterase (PDE) 3 inhibitor (MKS492) on the early and late
      responses to inhaled allergen in 18 atopic asthmatic subjects. METHODS: On three
      separate occasions, 2-4 weeks apart, patients were administered either placebo,
      20 mg or 40 mg of oral MKS492 as a single dose. After 90 min they inhaled a dose
      of allergen (grass pollen or D. pteronyssinus) that had been demonstrated to
      produce a 20% decrease in FEV1. Measurements of FEV1 were repeated at 30 min
      intervals over the subsequent 7.5 h. RESULTS: After placebo, allergen inhalation
      produced bronchoconstriction with a maximum mean minimum FEV1 of 75.9% (12.7)
      (mean [s.d.]) of post-saline baseline values and a late response developed in 13
      subjects (decrease in FEV1 > or = 15%). MKS492 (40 mg) increased the mean minimum
      % post-saline FEV1 at 30 min from 81.6% (14.0) for placebo to 93.1% (13.8),
      difference 11.5, 95% CI (2.6, 20.4). The mean minimum % post-saline FEV1 in the
      early response (0-2 h) was also increased by the 40 mg dose to 86.5% (11.8) vs
      77.9% (13.8) for placebo, but not by the 20 mg dose. Significant
      bronchodilatation was noted 90 min after dosing (pre-allergen) in the MKS492 40
      mg group. Late phase responses as assessed by 4 h % post-saline FEV1 was
      significantly improved by MKS 492 40 mg to 90.0% (6.3) vs 83.0% (12.4) for
      placebo-difference 7.0, 95% CI (0.1, 13.9), but again not by the 20 mg dose.
      Analysis of the area under the FEV1 response-time course curves showed non
      significant reduction in the late response after the 40 mg dose (placebo 159.0,
      134.8) vs 128.1, [81.5] for 40 mg). CONCLUSIONS: A novel PDE 3 inhibitor
      significantly decreases the early bronchoconstrictor response in asthma and
      attenuates the late response; effects that may be more marked at higher doses.

PMID- 9578189
TI  - Integrating clinical pharmacology teaching with general practice.
AB  - AIMS: To make Clinical Pharmacology teaching relevant and introduce students to
      therapeutic problems relevant to general practice. METHODS: Six topics in the
      'core curriculum' for Clinical Pharmacology were taught jointly by a Clinical
      Pharmacologist and General Practitioners (GPs). Formal teaching was reduced by
      issuing handouts containing copies of the overheads used. At least half the time
      was spent on interactive discussion of case histories. RESULTS: Students rated
      the sessions more highly than other Clinical Pharmacology teaching and were not
      disadvantaged in examinations. All participants enjoyed and learnt from the
      experience and the GPs gained confidence in their ability to teach. CONCLUSIONS:
      This simple method is ideal for teaching Clinical Pharmacology and Therapeutics.

PMID- 9578190
TI  - The airway effects of stopping regular oral theophylline in patients with asthma.
AB  - AIMS: We investigated whether the deterioration in asthma control reported
      following cessation of theophylline was due to tolerance to theophylline.
      METHODS: Eighteen subjects with mild stable asthma were given oral theophylline
      10 mg kg(-1) day(-1) or placebo for 2 weeks in a double-blind crossover study.
      FEV1 and PD20 histamine were measured before and 8 h after the first dose of
      treatment and 8, 32 and 56 h after the final dose. PD20 AMP was measured before
      treatment and 9 h after the final dose. RESULTS: Six patients did not tolerate
      theophylline. In the other 12 subjects there were no differences between
      treatments in daily PEF, symptom scores, rescue bronchodilator use, PD20
      histamine or FEV1 up to 8 h post treatment. Following withdrawal of theophylline
      there were significantly lower values for mean FEV1 (mean difference 0.151, 95%
      CI 0.03, 026) and PD20 AMP compared to placebo but no difference in other end
      points. CONCLUSIONS: The small rebound deterioration in lung function following
      regular treatment with therapeutic doses of oral theophylline is consistent with
      the development of tolerance.

PMID- 9578191
TI  - Are altered pharmacokinetics of non-steroidal anti-inflammatory drugs (NSAIDs) a
      risk factor for gastrointestinal bleeding?
AB  - AIMS: We hypothesised that pharmacokinetic factors might go some way to
      explaining the risk of major gastrointestinal haemorrhage with non-steroidal anti
      inflammatory drugs (NSAIDs), with bleeders exhibiting a reduced clearance of
      NSAIDs compared with non-bleeders and set out to investigate this. METHODS: Fifty
      patients presenting to hospital with acute gastrointestinal bleeding while taking
      piroxicam, indomethacin, diclofenac or naproxen and age, sex, musculoskeletal
      disease and drug matched community dwelling controls, up to two for each index
      case, who had not bled were recruited. Clinical details including duration of
      therapy were recorded. Bleeders discontinued the implicated NSAID at
      presentation, controls at least five half-lives before the study. Bleeders were
      contacted by letter 1 month after discharge and invited to take part and were
      studied after a median delay of 5 months. Subjects received an oral dose of their
      respective NSAID and venous blood was sampled, over a period determined by the
      half-life of the NSAID. Plasma concentrations were determined by high performance
      liquid chromatography. RESULTS: The median length of treatment for the index
      patients was 1 year (range 2 weeks--28 years) and for the control patients 2
      years (1 month--25 years), P<0.0005. There were no significant differences in
      peak plasma concentration, time to peak plasma concentration or area under the
      plasma concentration-time curve between bleeders or controls for any of the
      NSAIDs studied, apart from piroxicam Cmax being lower in bleeders at 2.07 mg l(
      1) than in controls at 3.21 mg l(-1), mean difference (95% CI) -1.14 (-1.83 - 
      0.48), P<0.005. CONCLUSIONS: The data failed to support the hypothesis that
      reduced clearance of NSAIDs, which results in higher plasma concentrations, is a
      risk factor for acute gastrointestinal haemorrhage.

PMID- 9578192
TI  - Vigabatrin: placental transfer in vivo and excretion into breast milk of the
      enantiomers.
AB  - AIMS: Vigabatrin is a new antiepileptic medication consisting of a racemic
      mixture of 50% active S enantiomer and 50% inactive R enantiomer. Since patients
      suffering from epilepsy may become pregnant, it is important to understand the
      extent of placental transfer of such medication. METHODS: During steady-state,
      vigabatrin enantiomer concentrations were measured in maternal and umbilical
      blood and in breast milk of two patients. RESULTS: The concentration ratios from
      the umbilical vein to maternal plasma were R:0.068, S:0.16; 4h25 min after drug
      administration (case 1) and R: 1.39, S: 0.91; 9h after drug administration (case
      2). The milk: plasma concentration ratio was lower than 1 at pre dose sampling in
      both cases, as well as 3 and 6 h post dose in one case. An estimate of the
      maximum amount of R and S enantiomers of vigabatrin that a suckling infant would
      ingest in a day is 3.6% and 1% of the weight-adjusted daily dose respectively.
      CONCLUSIONS: These results would suggest a slow placental transfer of the
      vigabatrin enantiomers and that the quantity ingested through milk is small.

PMID- 9578194
TI  - The way forward: nursing research or collaborative health care research?

PMID- 9578193
TI  - Effect of food on the pharmacokinetics of ropinirole in parkinsonian patients.
AB  - AIMS: Ropinirole is a specific non-ergoline dopamine D2-receptor agonist with
      antiparkinsonian properties. The pharmacokinetic parameters of ropinirole taken
      in the fasted condition were compared with those when it was co-administered with
      food. METHODS: This was an open, randomized, two sessions cross over study in 12
      patients with Parkinson's disease, comparing the steady-state pharmacokinetic
      profiles of ropinirole on two different study days: 'fasted' and 'fed'. RESULTS:
      The mean Cmax was lower in the 'fed' regimen than in the 'fasted' one (-25%,
      P=0.002). The median tmax was observed 2.6 h later in the 'fed' regimen than in
      the 'fasted' regimen (P<0.05). There was a slight but significant decrease in
      AUC(0,8 h) in the 'fed' regimen (P=0.03). CONCLUSIONS: Food decreases the rate of
      absorption of ropinirole, but has little effect on the extent of absorption.

PMID- 9578195
TI  - HIV in Eastern Europe.

PMID- 9578196
TI  - The debates emerging from the literature surrounding the concept of spirituality
      as applied to nursing.
AB  - This paper explores three debates surrounding the growing concept of spirituality
      as applied to nursing: 'Spirituality: in pursuit of conceptual and theoretical
      unity'; 'The demise of spirituality and the rise of secularism within nursing';
      and 'Spirituality: a unifying force at the foundation of holistic philosophy'.
      The debates reveal the complex and diverse nature of spirituality suggesting that
      there is no single authoritative definition. The debates challenge the nursing
      profession to develop a definition of spirituality which is broad enough to
      accommodate the uniqueness of all individuals.

PMID- 9578197
TI  - Process consent: a model for enhancing informed consent in mental health nursing.
AB  - Informed consent, essentially a legal doctrine, is designed to protect the rights
      of patients. However, in an area of practice such as psychiatry, informed consent
      imposes many problems if one considers it to be a static process. In this paper
      we propose that process consent, the type of consent considered essential in
      qualitative research projects, is not only appropriate but necessary for mental
      health nursing practice. This type of consent is an ongoing consensual process
      that involves the nurse and patient in mutual decision making and ensures that
      the patient is kept informed at all stages of the treatment process. We have used
      neuroleptic medications as an example throughout the paper and have suggested
      that seeking informed consent should be added to the role of the nurse in the
      mental health setting.

PMID- 9578198
TI  - Severe mental illness, statutory supervision and mental health nursing in the
      United Kingdom: meeting the challenge.
AB  - Within the United Kingdom a combination of limited resources and public fears
      about the behaviour of mentally ill people living in the community has led the
      government to prioritize those with severe mental illness. In support of this
      legislation has been passed which provides for those mentally ill deemed 'at
      risk' to be supervized in the community against their will. This supervisory role
      will be mainly undertaken by mental health nurses. Through examination of
      relevant British and American literature, this paper argues that mental health
      nursing at a national level lacks a defined role which the new legislation may
      provide, thereby enhancing the profession's voice in overall mental health policy
      formulation. Such a role, however, also poses important questions for mental
      health nurses' practice, their relationships with users, colleagues and the wider
      society. Such issues may have unforeseen negative consequences for users. It is
      argued that the legislation will pose important dilemmas for mental health nurses
      in these domains. It is argued that a proactive research agenda needs to be
      established which is relevant and of use to practitioners when confronted with
      issues in their supervision role. Areas for future research are suggested.

PMID- 9578200
TI  - Is befriending by trained volunteers of value to people suffering from long-term
      mental illness?
AB  - People who suffer from long term mental illness may be vulnerable to loneliness
      and isolation when living in community settings. Befriending by volunteers may be
      an effective way of combating such problems and helping clients to develop social
      networks. The findings of a small scale project to evaluate the views of people
      suffering from long term mental illness of an organized befriending scheme are
      reported. Nine subjects who suffer from severe mental illness were interviewed,
      all subjects felt befriending was helpful to them, and 67% of subjects thought it
      had improved their confidence when in social situations. Subjects who lived alone
      indicated a preference to see volunteers at home, whilst those who lived with
      carers preferred support in going out socially. The value of befriending schemes
      as part of community care services for this needy client group are discussed.

PMID- 9578199
TI  - Occupational stress and community mental health nursing: what CPNs really said.
AB  - The Claybury Nursing Stress Study assessed the levels of occupational stress
      experienced by both ward-based and community nurses. This paper presents the
      results obtained from a qualitative analysis of statements made by community
      psychiatric nurses during a questionnaire based interview. Key areas identified
      by CPNs as relevant to stress and coping are reported and suggestions for
      further, qualitative research in this area are made.

PMID- 9578201
TI  - Consumerism and health care: the example of fertility treatment.
AB  - This paper discusses the concepts of consumerism and the consumer of health care,
      and applies them to the example of fertility treatment, drawing on the health
      policy literature and data from a study of couples undergoing fertility
      treatment. It is argued that the concept of the consumer is a slippery one, that
      it provides only a partial view of being a patient, and that in particular it
      neglects emotional issues.

PMID- 9578202
TI  - Nursing in the dialysis unit: technological enframing and a declining art, or an
      imperative for caring.
AB  - Nursing in haemodialysis units has been well established since the 1960s.
      Technological developments, open patient selection methods and economic pressures
      have altered the dialysis unit to become increasingly busy, where demand
      outstrips availability. For nurses it has become akin to working on a 'production
      line' in order to meet the need for treatment. The increasing demand has required
      the nurse to become technologically skilled often to the detriment of caring.
      What emerges is the nurse enframed by technology where the caring of nurses is
      focused through the demand of getting the patients processed. Here is a dilemma
      where caring becomes a moral imperative in order to overcome the dehumanising
      effects of technology, and the future of the dialysis nurse comes into question.

PMID- 9578203
TI  - Pain and powerlessness: the experience of living with peripheral vascular
      disease.
AB  - Peripheral vascular disease (PVD) is a widespread condition, the most common
      manifestation being a gradual occlusion of the arteries of the legs due to
      atheroma, which results in symptoms of ischaemia such as intermittent
      claudication or rest pain, ulceration and gangrene. Treatment of the condition is
      palliative and reconstructive, and aims to salvage the limb, restore mobility and
      function, and relieve pain. It usually involves attempts to revascularize the
      affected limb, either by surgical procedures such as bypass grafting, or by
      percutaneous transluminal angioplasty or thrombolysis. In some cases, it may be
      necessary to amputate the limb or part of it. Despite the chronicity of PVD,
      little is known about the ways in which individuals with vascular disease cope
      with their condition and about the effect it has on their life. In this context
      the aims of this study were to explore the lived experience of peripheral
      vascular disease, in order to identify key themes and categories, using a
      phenomenological grounded theory approach. A sample of nine individuals was drawn
      from patients who had had vascular bypass surgery within the past 18 months. Data
      were collected using audiotaped one-to-one interviews and the researcher's field
      notes, and were validated with a group of experienced vascular nurses.
      Transcripts were analysed using open and axial coding techniques, and major and
      minor categories were identified and related to other data collected. It appeared
      that vascular patients experienced powerlessness in relation to the direct
      effects of their condition and in relation to its treatment modalities. The
      findings suggested that the 'acute' style of management of PVD often led to
      unrealistic expectations on the patient's part, which gave rise to the experience
      of powerlessness. The implications of these findings for the management of
      patients with PVD are discussed.

PMID- 9578204
TI  - Perceptions and practice of universal blood and body fluid precautions by
      registered nurses at a major Sydney teaching hospital.
AB  - Guidelines for universal blood and body fluid precautions (UBBFP) designed to
      protect health care workers from occupational exposure to blood borne pathogens
      have been developed by the US Centers for Disease Control. These guidelines have
      been adopted by the New South Wales Department of Health and all major Australian
      hospitals. To determine the degree of understanding and utilization of UBBFP by
      Australian nurses, 192 nurses were asked about UBBFP, recent occupational
      exposures and understanding of hepatitis B transmission. Seventy-three per cent
      of nurses stated they 'used UBBFP at all times', yet only 58% of these nurses
      stated they always used gloves when 'handling blood or blood equipment' and just
      85% reported always using 'gloves to clean up urine and faeces'. Overall 146
      (76%) nurses experienced 230 occupational exposures (168 mucocutaneous, 48
      percutaneous) in the previous 6 months. These were more common in men (P=0.024)
      and in operating theatres (95% of nurses) and high dependency units (88%).
      Percutaneous exposures were significantly more frequent in nurses who stated they
      did not wear gloves when handling blood/blood equipment (P=0.036), whereas
      mucocutaneous exposures were significantly more frequent among nurses who stated
      they do not adhere to UBBFP at all times (P=0.005). Eighty-three per cent of
      nurses experiencing exposures did not report all of them. In this study knowledge
      and adoption of UBBFP translated directly into lower risk for an occupational
      exposure. It is concluded that educational strategies to improve understanding
      and adoption of UBBFP by nurses are required.

PMID- 9578205
TI  - Attitudes of professionals, students and the general public to HIV/AIDS and
      people with HIV/AIDS: a review of the research.
AB  - This paper provides a review relating to the attitudes of health care
      professionals, students and the general public to HIV/AIDS and people with
      HIV/AIDS. This is done by describing the literature on attitudes to HIV and AIDS
      in three fields of research: medicine/nursing, psychology and the social
      sciences. In addition, we look at the countries in which research has been
      conducted in these issues and at the variety of tools and methodological
      approaches used and at the participants studied. The review shows that, during
      the 1990s, the research interest in issues related to HIV/AIDS attitudes has
      rapidly increased. Most of the work on HIV and AIDS has been done in the United
      States, with the main focus on empirical research using questionnaires. The
      attention has mostly been on students and their attitudes to AIDS/HIV and sexual
      behaviour, but increasing interest has also been shown in the attitudes of health
      care personnel and students. As it seems that attitudes have been highly
      resistant to change, more consideration needs to be given to finding appropriate
      ways of educating the general public, students and health care professionals. A
      comprehensive analysis is also needed of the different tools used in measuring
      attitudes and in international comparisons of the attitudes of adolescents,
      health care professionals and students towards AIDS and AIDS patients.

PMID- 9578206
TI  - Adolescents' perceptions of physicians, nurses, parents and friends: help or
      hindrance in compliance with diabetes self-care?
AB  - Although compliance with self-care amongst adolescents with diabetes is known to
      be problematic, this issue has rarely been examined from the perspective of young
      diabetics themselves. The purpose of the study was to explore how adolescents
      with diabetes perceived the actions of physicians, nurses, parents and friends in
      relation to compliance with self-care. Fifty-one young diabetics aged from 13 to
      17 responded to a questionnaire concerning compliance and were interviewed on the
      topic of compliance. Interview data were analysed by content analysis. The
      categories obtained were quantified and the relationship between compliance and
      the actions of physicians, nurses, parents and friends analysed by cross
      tabulation. Interviews with 51 adolescents showed that the actions of physicians,
      nurses and parents described as motivating were associated with better
      compliance. Good compliance was also more evident when parental actions were
      perceived as accepting. Young diabetics whose friends offered silent support, or
      who viewed friends as irrelevant, were more likely to report good compliance. In
      contrast, physicians' actions described as routine/negligent, disciplined control
      by parents, and domination by friends were linked with poor compliance.

PMID- 9578207
TI  - Importance of information following myocardial infarction: a study of the self
      perceived information needs of patients and their spouse/partner compared with
      the perceptions of nursing staff.
AB  - A non-experimental research design using questionnaires, was undertaken to find
      out what information out of that commonly given following myocardial infarction
      (MI), patients and their spouse/partners rate as being most and least important.
      These results were then compared with the results obtained from nurse subjects,
      who were given the same instrument to complete. Eighteen subjects were recruited
      for each of the three subject groups. Results indicated that some congruency
      existed between the three groups in terms of what they perceived as the most and
      least important categories of information. Yet, the scores for some informational
      categories included on the instrument, were significantly different between the
      nursing and two other groups (P < 0.01). However, in relation to the patient and
      spouse/partner groups, only a weak difference (P < 0.10) was found for the
      category 'dietary information'. These findings and others are discussed, and
      recommendations are made for improving the information giving process post-MI.

PMID- 9578208
TI  - Loss: an analysis of a concept of particular interest to nursing.
AB  - The term 'loss' is used frequently in the nursing literature and by nurses in the
      clinical setting. However, loss as a concept has not been defined
      comprehensively. In this paper, an attempt will be made to analyse the concept.
      The paper will begin with an overview of approaches to concept analysis.
      Subsequent sections include a literature review examining current and classic
      usage of the concept. General and specific definitions of loss provide a template
      for discussion. The paper will conclude with the identification of critical
      attributes for the concept which will form the basis for an exploration of
      explicit empirical referents.

PMID- 9578209
TI  - The case for case studies in nursing research: the problem of generalization.
AB  - This paper examines the logic of generalizing from case studies and other
      nonrepresentative samples. It is argued that the generalizability of such
      research is often underestimated, because of a fundamental confusion about two
      quite distinct logical bases upon which generalizations can be made: empirical
      and theoretical. It is suggested that once it is accepted that theoretical
      generalizations do not depend upon representativeness for their validity, the
      full value of case study, and other small-scale qualitative research to nursing
      and other health care disciplines, can be appreciated.

PMID- 9578211
TI  - Barriers to and facilitators of research utilization, as perceived by a group of
      registered nurses in Sweden.
AB  - A survey was conducted to describe registered nurses' (n = 237), perceptions of
      the barriers to and the facilitators of research utilization at two hospitals in
      Sweden. A questionnaire, Barriers and Facilitators to Using Research in Practice
      developed by Funk et al., was used to collect the data. The major barriers to
      research utilization were that the research is not readily available along with
      inadequate facilities for implementation of research findings, lack of competent
      colleagues with whom to discuss research, lack of time for reading and
      implementing research findings and the nurses lack of authority in the
      organization. The nurses who had studied research methods in their basic nursing
      education, seemed to perceive fewer barriers than those who had not. The
      facilitating factors most frequently suggested by the nurses were diverse models
      of education to increase their knowledge of research methods and to develop
      skills in evaluating research findings. The allocation of resources for education
      and implementation of research findings in clinical practice, in addition to
      special positions in clinical practice for nurses with scientific qualifications,
      were also suggested.

PMID- 9578210
TI  - Playing the power game for qualitative researchers: the possibility of a post
      modern approach.
AB  - The later work of Wittgenstein (1953) takes language and meaning as arising in
      use. A local 'grammar' is created. Ethical/research awarding committees have
      developed, and clashing, meanings about what constitutes 'good' research. The
      fixed rule language game of the committee is implicitly powerful because it is
      part of well-rehearsed societal narratives which equate science and knowledge.
      This creates a force on the qualitative researcher to conform to the
      authoritative grammar which it is difficult to counter. In these circumstances,
      qualitative researchers may choose to inhabit two, parallel research universes by
      'storying' their research proposal according to the audience. But a question
      arises as to whether ethical approval has been gained when a 'Trojan horse'
      approach is used. Moving between worlds involves the researcher living with a
      dual identity. The postmodernist movement away from structure, form and singular
      truth is seen as setting a context for a new archaeology of knowledge which
      transcends good/bad dichotomies in relation to research. The qualitative
      researcher is encouraged to enter into dialogical communication with committees
      with the hope that a shared grammar may emerge.

PMID- 9578212
TI  - The delivery of quality nursing care: a grounded theory study of the nurse's
      perspective.
AB  - This grounded theory study explored and described the delivery of quality nursing
      care from the perspective of nurses. Data were gathered by tape recorded
      interviews, published literature and some participant observation. Ten registered
      nurses from an acute-care public hospital located in Perth, Western Australia
      were interviewed. Twelve additional transcripts from interviews conducted by
      postgraduate students were also used. Quality nursing care was perceived to
      relate to the degree to which patients' physical, psychosocial, and extra care
      needs were met. The consequences of quality care were interpreted as 'therapeutic
      effectiveness', where the therapy provided by nurses was perceived to positively
      affect patients' healing. This was gauged by the patient's psychosocial and
      physical response to illness, safety, and satisfaction. Therapeutic effectiveness
      was facilitated by the development of positive relationships between nurses and
      patients, nurse's positive attributes and competent practices, as well as a
      functional nursing team. The problem of nurses' inability to consistently provide
      quality nursing care to all patients was identified. Insufficient time (caused by
      a lack of human and physical resources) was perceived as the main reason for
      this. Dissatisfaction and stress in nurses was related to this problem. To deal
      with this, nurses used a process named 'selective focusing'. Work was planned to
      most effectively utilize the time available, within the parameters of safety.
      Implications for nursing practice, education and management are discussed, and
      directions for further research are provided.

PMID- 9578213
TI  - Misinterpretive phenomenology: Heidegger, ontology and nursing research.
AB  - This paper argues that Heidegger's phenomenology does not have the methodological
      implications usually ascribed to it in nursing literature. The Heidegger of Being
      and Time is not in any sense antagonistic to science, nor does he think that
      everydayness is more authentic, more genuine, than scientific enquiry or
      theoretical cognition. It is true that social science must rest on interpretive
      foundations, acknowledging the self-interpreting nature of human beings, but it
      does not follow from this that hermeneutics exhausts all the possibilities.
      Positivist approaches to social science are certainly inconsistent with
      Heidegger's ontology, but realist approaches are not and structuration theory, in
      particular, can be seen as a sociological translation of his ideas. Social
      enquiry in nursing is not therefore confined to studies of lived experience.
      Indeed, lived experience research constitutes not a realization, but rather a
      betrayal, of Heidegger's phenomenology, being thoroughly Cartesian in spirit.

PMID- 9578214
TI  - The Tredgold model of nursing.
AB  - A nursing model is a framework upon which nurses can base their approach to care.
      A model may expand a philosophy into the abstract as it encompasses the nurses'
      beliefs about their role, the patient's involvement and the meaning of the
      interactions between the two. On Tredgold ward we decided to write our own model
      as established frameworks did not entirely reflect our approach. We used the
      elements of British nursing models as described by Brown (1989) as the basis for
      our work and in doing so additionally wrote our own definition of nursing. The
      process has led to a more cohesive and confident team with a clearer sense of
      direction. This has increased our standing with colleagues and educationalists.

PMID- 9578215
TI  - An adjusted version of Kohlberg's moral theory: discussion of its validity for
      research in nursing ethics.
AB  - Critics of Kohlberg's moral theory today focus on the content of his theory and
      more specifically on its justice-orientated moral concept. This has led to the
      well-known 'justice-care debate'. The purpose of this article is to critically
      examine the validity of Kohlberg's moral theory for research in nursing ethics
      from a caring perspective (referring to the content) as well as from a cognitive
      structural perspective (referring to the basic assumptions of the model). The
      analysis points to the usefulness and value of the cognitive-structural model to
      empirically study nurses' ethical behaviour; the content of Kohlberg's model,
      however, needs to be adapted by adding a caring perspective as well as some
      personal and situational variables. An adjusted version of Kohlberg's model is
      proposed and discussed.

PMID- 9578216
TI  - Connection: an exploration of spirituality in nursing care.
AB  - This paper aims to explore the meaning of spirituality in relation to nursing
      care using concept synthesis. Walker and Avant give three ways in which concept
      synthesis can occur: discovering new dimensions to old concepts, searching for
      similarities and discrepancies among sets of related concepts, and observing
      previously undescribed phenomena. It is the first two of these methods which have
      been used here. The phenomena that emerged from a reading of the literature
      around spirituality were meaning, presencing, empathy/compassion, giving hope,
      love, religion/transcendence, touch and healing. These phenomena were studied in
      order to sort them into fewer categories. They all appeared to be products of a
      relationship, some physical (presencing, touch and healing), and others emotional
      (meaning, empathy/compassion, hope, love, and religion/transcendence). Some of
      the phenomena appeared to fit in both categories, especially healing, which could
      be of a physical or emotional/spiritual nature. Once the two main categories had
      been arranged, it was obvious that a split between psyche and soma was not
      appropriate for labelling the spiritual dimensions of nursing care, as the
      original definition of spirit was something which motivated the body. Spiritual
      care is inseparable from physical, social and psychological care because together
      they form the whole (Bradshaw 1994 p. 282). The two categories were then
      collapsed into one and given the label 'connection'.

PMID- 9578217
TI  - Establishing an international network on nurses' clinical reasoning.
AB  - A recent review of the relevant literature indicates that different approaches to
      the exploration of nurses' clinical reasoning are being adopted in North America,
      Australia and the United Kingdom. These differing approaches, which tend to
      cluster chronologically and which include decision analysis, information
      processing and skills acquisition theory and their limitations will be outlined;
      it will be argued that it is through their conflation that nurses' collective
      understanding of nurses' clinical reasoning is deepened. The author is attempting
      to develop an international network of nurse scholars interested in clinical
      reasoning with the aim of achieving this. The purposes of this network will be to
      facilitate international collaboration to expedite both the growth of knowledge
      related to nurses' clinical reasoning and the development of programs of
      international comparative research related to it. The setting up of this network
      and progress to date is described.

PMID- 9578218
TI  - A survey of psychiatric nursing practice in two inner city acute admission wards.
AB  - In response to the British government's Review of Mental Health Nursing this
      paper reports on a study which examined nursing practice in two inner city acute
      admission wards. Eight nursing staff maintained a record of their activities over
      a 7-day period according to four operationalized variables. Qualitative detail
      was also collected to enable the specification of activities. The amount of time
      available for patient contact work is calculated and those activities which
      currently restrict opportunities for experienced nursing staff to have
      therapeutic interactions with their patients are identified. The findings do not
      differ markedly from earlier studies and some tentative conclusions are drawn
      concerning the therapeutic milieu within an inner city psychiatric in-patient
      facility.

PMID- 9578219
TI  - Cancer patient and staff ratings of the importance of caring behaviors and their
      relations to patient anxiety and depression.
AB  - Patient and staff ratings of the importance of caring behaviours (Caring
      Assessment Instrument, CARE-Q) were studied and related to ratings of patient
      levels of anxiety and depression (Hospital Anxiety and Depression Scale) in 53
      cancer patient-staff dyads. Both groups perceived anticipatory and comforting
      behaviours to be among the three most important. Patients considered staff
      explanation and facilitation as well as anticipation to be more important than
      did staff. Staff rated accessibility and comforting as more important than did
      patients. Patient and staff ratings of the importance of staff accessibility were
      negatively correlated. Thus, patient and staff 'did not agree strongly on the
      importance of several types of caring behaviours. Neither patient nor staff
      ratings of the importance of caring behaviours were associated with their ratings
      of the levels of anxiety or depression of specific patients. The results suggest
      that patient-staff communication requires specific knowledge and skills to make
      staff accurately judge what is important in making patients feel cared for.

PMID- 9578221
TI  - Synthesis in nursing knowledge: an analysis of two approaches.
AB  - The need for synthesis in nursing knowledge development has been attested to by
      many authors. It is consistent with nursing's holistic focus and is the mark of a
      mature discipline. This paper examines two approaches to synthesis: the use of
      multiple paradigms and the possible emergence of a new paradigm based on chaos
      theory. It argues that in their current form both approaches have flaws and
      neither achieves synthesis as it is here defined. However, both may make
      significant contributions to the development of nursing knowledge.

PMID- 9578220
TI  - The impact of management of change projects on practice: a description of the
      contribution that one educational programme made to the quality of health care.
AB  - This paper is based on the authors' experience of teaching and supervising the
      first intake of the management unit of the diploma for charge nurses offered by
      the Department of Professional Development and Training, Glasgow College of
      Nursing and Midwifery, Glasgow, Scotland. The students on this course undertake a
      project comprising of a documented research-based action plan aimed at the
      achievement of a selected topic for change directly linked with their practice.
      All the students except one were G grade charge nurses from a wide variety of
      clinical backgrounds. This paper will briefly consider the work of Barriball et
      al. who suggest categories of outcomes of continuing professional education. This
      is contrasted with Scheller, who highlights three problems when attempting to
      measure the impact of continuing education on practice. Despite these problems,
      it is beneficial to attempt to consider the impact of continuing professional
      education on practice. The work of Francke et al. will be featured in which they
      ascertain the determinants of changes in nurses' behaviour after continuing
      professional education. The authors believe that the management of change
      project, undertaken by the students, enhances the possibility that knowledge
      gained from the management unit will impact on their practice. Two examples of
      students' projects will be used to support the paper. The first concerns changing
      to a 12-hour shift pattern in an intensive care setting and the second relates to
      the implementation of the named nurse system.

PMID- 9578222
TI  - Can chemical softening agents minimize cavity enlargement during removal of
      failed anterior resin composite restorations?
AB  - This in-vitro investigation sought to identify the most effective softening
      agents for three commercial anterior resin composites (Prisma APH, Brilliant and
      Blend-a-Lux) from four potential agents (75% ethanol, polyacrylic acid, acetone
      and acetic acid), selected as having close solubility parameter values to BIS
      GMA. The Vickers microhardness test was applied to samples before and following a
      180 s application of each agent. In addition, the degree of cavity enlargement
      following removal of resin composite restorations, aged by thermocycling, was
      assessed by image analysis. Using the same method the influence of both colour
      match and the 180 s application of softening agents, in the optimum
      chemical/material combinations, upon this was determined. Analyses of variance
      revealed that significant (P < 0-01) reductions in surface microhardness occurred
      when 75% ethanol was applied to Prisma-APH and acetic acid to Blend-a-Lux.
      Removal of restorations of all materials resulted in highly significant (P <
      0.001) increases in cavity size. Application of either 75% ethanol to Prisma-APH
      restorations or acetic acid to Blend-a-Lux did not alter this result.
      Thermocycling only produced a significant (P < 0.01) (McNemar Test) deterioration
      in shade match of the Prisma APH restorations but analyses of variance, for all
      materials, revealed that the observed changes in colour match had no significant
      (P < 0.05) effect upon the degree of cavity size enlargement. It is concluded
      that the application of softening agents to reduce cavity enlargement is not a
      viable clinical option.

PMID- 9578223
TI  - Effect of edentulousness on mandibular size and condyle-fossa position.
AB  - Modern imaging methods make possible the more precise examination of the
      complicated bony structure of the temporomandibular joint (TMJ) and the
      performance of cephalometric analysis. The aim of our study was to analyse the
      effect of edentulousness on the mandibular size and the condyle-fossa position
      using roentgencephalograms and axial computed tomography (CT) scans. The study
      group consisted of 20 edentulous patients (14 women, six men, mean age 60 years)
      whose mean period of edentulousness was 20 years (range 3-34 years). A CT
      examination of their TMJs was performed and roentgen-cephalograms in 16 of this
      group were taken after prosthetic treatment. Sixteen dental students were chosen
      according to sex as controls. Earlier CT scans of 49 dentate subjects of both
      sexes were used as controls for the analysis of bicondylar asymmetry. The
      position of the glenoid fossa was more anterior in edentulous subjects than in
      dentate ones and its anterior position correlated significantly (P < 0.02) with
      the period of edentulousness, a finding which has not been confirmed before. It
      can be concluded that the fossa is a remodelling unit as a part of the functional
      entity when the function is altered dramatically as in the case of edentulous
      patients.

PMID- 9578224
TI  - The adverse effect of commercial dentine-bonding systems on the skin of guinea
      pigs.
AB  - It was widely known that 2-hydroxyethyl methacrylate (2-HEMA) can cause contact
      dermatitis. Commercially available dentine primers and dentine bonding agents
      that contain 2-HEMA are widely used. The purpose of this study was to investigate
      the cumulative irritation and delayed hypersensitivity caused by commercial
      dentine bonding systems when applied to the skin of guinea pigs. We have
      concluded that almost no dentine bonding systems cause cumulative irritation, but
      some commercially available dentine bonding systems may produce delayed
      hypersensitivity.

PMID- 9578225
TI  - Oral stereognosis in edentulous subjects rehabilitated with complete removable
      dentures.
AB  - Oral stereognosis was analysed in a group of edentulous subjects rehabilitated
      with complete removable dentures. Stereognosis was evaluated with and without the
      denture in place. The results showed that the older subjects had poorer
      stereognostic ability than the younger ones, whereas the duration of edentulism
      appeared not to influence this ability. The presence of a correct prosthetic
      rehabilitation appeared to improve stereognostic ability. Subjects with poorer
      stereognostic ability appeared more satisfied with their rehabilitation than did
      those with better stereognostic ability.

PMID- 9578226
TI  - Evaluation of chewing activity in the elderly person.
AB  - In the present study, we examined the chewing performance of 70 elderly persons.
      Self-assessment of chewing problems and clinical classification using the
      modified Eichner index showed little correlation (Kappa value = 0.28; 95%
      confidence interval (CI) = 0.05-0.51). The sensitivity and specificity were 0.52
      and 0.76, respectively. On the other hand, the mastication score determined by
      evaluation of a questionnaire on food intake and classification using the
      modified Eichner index showed high agreement (Kappa value = 0.73; 95% CI = 0.50
      0.96). The sensitivity and specificity were 0.76 and 0.95, respectively. The
      mastication score showed significant correlation with other masticatory functions
      such as maximum biting force, occlusal contact area and the number of missing
      teeth (P < 0.01). These results suggest that the use of a questionnaire on food
      intake would be informative for epidemiological surveys of chewing activity in
      the elderly.

PMID- 9578227
TI  - Correlation of the characteristics of temporomandibular joint and tooth contact
      sounds.
AB  - In this study tooth contact sounds have been compared with temporomandibular
      joint (TMJ) sounds elicited during opening and closing movements. One hundred and
      eight subjects were instructed to open as far as possible and then close with
      sufficient force to produce a tooth contact sound. At least four cycles from each
      subject were recorded on tape, The first and last sounds in the recording were
      the tooth contact sounds, these were identified automatically. The mean duration
      and rise time of each tooth contact sound was calculated and their standard
      deviations for each subject were calculated to give a measure of the
      reproducibility. The number and mean amplitude of TMJ sounds occurring during
      tooth separation were also calculated for each cycle. Highly significant
      correlations were found between the number and amplitude of the TMJ sounds within
      a cycle and the duration and rise time, and particularly their standard
      deviations. Acoustic quiescence during the open-close cycle was associated with
      short, reproducible tooth contact sounds characterized by a short rise time. The
      longest and most variable tooth contact sounds were associated with TMJ sounds in
      all three phases of the open-close cycle. This supports previous clinical
      findings associating occlusal interferences with TMJ dysfunction.

PMID- 9578228
TI  - Curing depth of a composite veneering material polymerized with seven different
      laboratory photo-curing units.
AB  - Properties of laboratory-cured composite materials are affected by the type of
      activation system as well as by the photo-curing unit light source. This study
      examined curing depth of a composite veneering material polymerized by means of
      various photo-curing units with the aim of evaluating the curing performance of
      the light sources. A microfilled composite material designed for prosthetic
      veneer was cured with seven photo-curing units. The light sources of the units
      were halogen/fluorescent, xenon, metal halide, fluorescent, halogen, halogen and
      mercury lamps. Exposure periods were 20, 30, 60 and 90 s. The curing depth of the
      material was determined using the method described by the International
      Organization for Standardization (ISO 4049). Two-factor analysis of variance
      revealed that the depth of cure was influenced both by the type of curing unit
      and by the exposure period (P = 0.0001). Among the seven photo-curing units, a
      metal halide curing unit consistently exhibited the greatest depth of cure. For
      all units, longer exposure increased the depth of cure.

PMID- 9578229
TI  - The effect of three different recording materials on the reproducibility of
      condylar guidance registrations in three semi-adjustable articulators.
AB  - Sagittal condylar guide settings of three semi-adjustable articulators: WhipMix,
      Hanau 158 and Denar Mark II were compared using registrations of base plate wax,
      copper wax and self-curing acrylic resin in two subjects. Four-way ANOVA showed
      differences between instruments (P < 0.0001), materials (P < 00001),
      registrations (P < 0.0001), and no difference between operators. Mean differences
      between materials were 3 degrees and 6 degrees within the range of registration
      and articulator variability. Denar Mark II gave the highest values, Hanau 158 the
      lowest with pantronic values generally lower than articulator settings. Neither
      acrylic nor copper wax were superior to base plate wax. This and previous studies
      show low reproducibility and variability between instruments, occlusal records
      and registration material.

PMID- 9578231
TI  - Flexural strength of a provisional resin material with fibre addition.
AB  - The effect of fibre addition on the flexural strength of a resin was studied. A
      provisional material (ALIKE; GC America Inc.) was used as the control and
      resinous matrix. Silane treated glass fibre was selected for the reinforcing
      treatment. In order to determine the geometric influence on the strength, ordered
      fibres (1 w/o) were immersed within a resinous matrix in four different
      locations. In addition, randomly dispersed fibres, 5 mm in length, were blended
      at 1 w/o up to 8 w/o with acrylic powder and moulded into rectangular specimens
      (34 mm x 9 mm x 8 mm) with P:L = 2:1. Ten specimens were prepared for each group.
      A three-point flexural test was run using a span of 25 mm at a rate of 5 mm/min.
      The strength values were collected and analysed with ANOVA and Scheffe tests. The
      strengths of the specimens with orientated fibre addition ranged from 49.4 (s.d.
      = 5.7) to 64.5 (6.7) MPa and the control was 54.3 (4.0) MPa. In the dispersed
      groups, the strengths obtained ranged from 55.9 (5.9) to 87.3 (7.9) MPa. The
      results disclosed that inclusion of orientated fibres horizontally on the tension
      side of the specimens significantly improved the flexural strength compared with
      the control (P < 0.05). An optimal strength was obtained in the group of
      provisional resin containing 5 w/o dispersed fibre. Incorporation of glass fibres
      significantly improved the flexural strength of the resin and the dispersed
      method is more efficient than the orientated inclusion method.

PMID- 9578230
TI  - Comparison of four different denture cushion adhesives--a subjective study.
AB  - Four cushion adhesives (Fittydent I; Fittydent II, introduced as an advanced
      formula; Protefix; and Seabond) were compared clinically through patients
      subjective evaluations. Maxillary dentures of 32 patients were relined and the
      mandibular dentures were scored by Kapur index before the application of
      different treatments. The cushion adhesives were used only with the existing
      mandibular prosthesis. The four treatments were applied to the patients in groups
      of 8 by allocating each group randomly to one of the four sequences of treatments
      determined by latin square design. Each patient took each treatment only once.
      The adhesives were applied by the authors as recommended by the manufacturers.
      Patients used each material for 24 h and, through a questionnaire, they evaluated
      the seven following aspects of each different cushion material: retention,
      duration of retention, effects on ability to chew, effects on other oral
      functions, cleansing of dentures, cleansing of gums, and an overall evaluation of
      materials. Both Fittydent products significantly improved denture retention and
      the ability to chew. The patients who expressed 'much better' chewing with
      Fittydent products, had mandibular dentures rated poor or fair.

PMID- 9578232
TI  - Fat, plain, but not friendless: self-esteem and peer acceptance of obese pre
      adolescent girls.
AB  - OBJECTIVES: Poor self-esteem is assumed, but not consistently found, in obese
      children and adolescents. The aims of this study were a detailed analysis of body
      weight influences on self-esteem and peer acceptance in pre-adolescent girls.
      DESIGN: A cross-sectional comparison of girls in four weight (body mass index
      [BMI]) groups; underweight (< 10%), normal weight (10-85%), overweight (85-95%),
      and obese (> 95%). MEASURES: Assessments of body weight and height, body shape
      preference, self-esteem and peer nominations of popularity and attractiveness
      were collected from 313 girls aged 9y. RESULTS: Obese and overweight girls had
      significantly lower physical appearance and athletic competence self-esteem than
      their normal weight peers. Body weight had no impact on girls' rated importance
      of self-esteem domains. Heavier girls were significantly less likely to be peer
      nominated as pretty, but did not differ in their popularity. CONCLUSIONS: Prior
      to adolescence, physical appearance rather than global self-esteem is affected by
      overweight, and popularity preserved. Further research is required into the
      mechanisms of peer influence, and its consequences, in obese and overweight young
      adolescents.

PMID- 9578233
TI  - Fasting gall bladder volume and lithogenicity in relation to glucose tolerance,
      total and intra-abdominal fat masses in obese non-diabetic subjects.
AB  - OBJECTIVE: To investigate whether total body fat mass or fat distribution and
      associated metabolic disturbances in glucose and lipid metabolism influence the
      well known gallstone pathogenetic factors in obese subjects in order to explain
      why some obese subjects develop gallstones and some do not. DESIGN: Cross
      sectional study of gallstone pathogenetic factors, body composition, fat
      distribution, glucose and lipid metabolism. SUBJECTS: 57 healthy overweight
      subjects (aged 26-64y, body mass index (BMI) 30-45 kg/m2). MEASUREMENTS: Total
      and intra-abdominal fat masses were measured by dual X-ray absorptiometry and
      abdominal CT scanning, respectively. The lithogenic index was measured in
      aspirated bile. The gallbladder volume was determined by ultrasound and the
      gallbladder ejection fraction% by dynamic cholescintigraphy. Plasma
      cholecystokinin (CCK) concentrations during a meal were measured with a specific
      radioimmunoassay. Insulin sensitivity was measured by the Minimal Model and
      glucose tolerance by an oral glucose tolerance test (OGTT). Serum lipid
      concentrations were measured by standard methods. RESULTS: The gallbladder volume
      in the fasting state increased with increasing intra-abdominal fat mass (P=0.006)
      and was increased in subjects with impaired glucose tolerance (41 vs 27 ml,
      P=0.001). The lithogenic index was > 1 in all subjects and correlated with total
      fat mass (P=0.04). CONCLUSION: Gallstone pathogenesis in obesity seems to be
      influenced by the total body fat mass and its regional distribution possibly via
      mutual association with the glucose tolerance.

PMID- 9578234
TI  - Assessment of selective under-reporting of food intake by both obese and non
      obese women in a metabolic facility.
AB  - OBJECTIVE: To investigate the degree of bias in under-reporting of food intake in
      obese and non-obese subjects, hypothesising that under-reporting may be selective
      for either macronutrient content (carbohydrate (CHO), fat, protein, alcohol),
      specific food types or eating occasions (meals, snacks). DESIGN: Thirty-three
      women (18 obese, 15 non-obese) were recruited to a long-stay metabolic facility
      for 24h. Ad libitum food intake was covertly measured throughout the study and a
      reported food intake completed at the end of 24h. RESULTS: Reported total daily
      energy intake was significantly lower than measured intake. Whilst meals were
      accurately reported, energy from snack foods eaten between meals was
      significantly under-reported. (P< 0.001) Reported total carbohydrate and added
      sugar intakes were significantly lower than measured, whilst reported protein and
      fat intakes were not significantly different from measured. Reported alcohol
      intake was also considerably lower than measured, but high variability prevented
      significance. CONCLUSIONS: In both obese and non-obese women the major cause of
      under-reporting, as assessed by covert study design in subjects restricted within
      a metabolic facility, is the failure to report between-meal snack foods. There is
      some evidence for increased under-reporting in high CHO, but no evidence of a
      bias in under-reporting towards high fat or high protein foods.

PMID- 9578235
TI  - Visceral fat as a main determinant of plasminogen activator inhibitor 1 level in
      women.
AB  - OBJECTIVE: To substantiate in a premenopausal population of women, the link
      between visceral adipose tissue and circulating plasminogen activator inhibitor 1
      (PAI-1) levels. DESIGN: Study of correlations between anthropometric parameters
      and PAI-1 and evaluation of the changes induced by weight loss. SUBJECTS: Forty
      two healthy pre-menopausal women (aged 18-51 y, with a wide range of body mass
      index (BMI, 21-48.8 kg/m2). Thirteen women were evaluated after weight loss
      (6.6+/-3.3 kg). MEASUREMENTS: BMI, waist and hip circumferences. Total,
      subcutaneous and visceral adipose tissue areas at the L3-L4 level by computed
      tomography. Insulin, cholesterol, triglyceride, HDL cholesterol, PAI-1 activity,
      PAI-1 antigen and tissue plasminogen activator (tPA) antigen. RESULTS: PAI-1
      activity, PAI antigen and tPA antigen were positively correlated with visceral
      adipose tissue, but not with subcutaneous adipose tissue. This correlation was
      independent of insulin or triglyceride levels. The amount of visceral adipose
      tissue explained 28% of the PAI-1 activity variance. Weight loss confirmed this
      link, PAI-1 diminution being correlated only with visceral adipose tissue loss
      and not with total fat, insulin or triglyceride decrease. CONCLUSION: This study
      suggests, like in vitro studies, that visceral fat may be an important
      contributor to the circulating PAI-1.

PMID- 9578236
TI  - Orchiectomy and response to testosterone in the development of obesity in young
      Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats.
AB  - OBJECTIVE: Withdrawal of testosterone prevents the development of hyperglycaemia
      in male Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats, a model of non-insulin
      dependent diabetes mellitus (NIDDM), but the exact mechanism has not been
      established. The present studies were undertaken to examine a possible role of
      testosterone in the development of obesity in young OLETF rats who have not shown
      marked hyperphagia. METHODS: Body weight, food intake and circulating
      concentrations of metabolic factors including immunoreactive leptin (IRL) were
      measured at five weeks of age in young male OLETF rats and their lean controls,
      Long-Evans-Tokushima-Otsuka (LETO) rats. At six weeks of age, both LETO and OLETF
      rats were bilaterally orchiectomized (Orchx) and half of each group implanted
      with a silastic tube containing testosterone. After a three week observation
      period, all animals were killed and circulating concentrations of metabolic
      factors and the ob gene expression in retroperitoneal white adipose tissues were
      measured. RESULTS: Body weight and 24h food intake were already increased in
      OLETF rats at five weeks of age. Serum testosterone concentrations were
      significantly lower in OLETF rats than in LETO rats. Expression of the ob gene
      was significantly decreased in the retroperitoneal white adipose tissue of OLETF
      rats, and their serum IRL concentrations were lower. Food intake and body weight
      gain for three weeks after the operation were significantly lower in the Orchx
      group of OLETF rats than in the sham-operated group. Hyperglycaemia, accompanied
      by hyperinsulinaemia, was attenuated by orchiectomy in OLETF rats. Circulating
      IRL concentrations were significantly higher in OLETF rats than in LETO rats and
      decreased by orchiectomy. Testosterone supplement reversed all of the changes
      caused by orchiectomy in OLETF rats. In contrast, the changes, which were
      observed after orchiectomy in OLETF rats, were not obvious in LETO rats.
      CONCLUSION: The present data indicate that testosterone plays a role in the
      development of obesity and NIDDM in young OLETF rats, but that changes of leptin
      production in white adipose tissue may not be important in the development of
      obesity in young OLETF rats.

PMID- 9578237
TI  - Effects of phentermine on striatal dopamine and serotonin release in conscious
      rats: in vivo microdialysis study.
AB  - OBJECTIVE: To measure the effects of phentermine, an appetite supressant, on the
      release of brain dopamine (DA) and serotonin (5-HT) into striatal dialysates of
      freely moving rats. DESIGN: Microdialysis and high performance liquid
      chromatography. SUBJECTS: Unanesthetized rats. MEASUREMENTS: Samples collected
      every 20 min were assayed for both neurotransmitters in a single run, using high
      performance liquid chromatography with electrochemical detection. RESULTS:
      Baseline levels of DA and 5-HT in dialysates were 56+/-16 and 3+/-0.6 fmol/20
      microl, respectively. Administration of phentermine (2 or 5 mg/kg) increased
      dialysate DA concentrations to 147+/-17% (P < 0.01) and 320+/-89% (P < 0.01) of
      baseline, respectively, without significantly affecting 5-HT concentrations.
      Pretreatment with tetrodotoxin (TTX, 60 min, 1 microM), which abolished the basal
      release of DA and 5-HT into striatal dialysates, diminished the increase in DA
      concentrations induced by phentermine, but did not completely block it.
      Phentermine (2 or 5 mg/kg, i.p.) still stimulated DA release to 27+/-13% and 85+/
      15% of baseline, respectively, in the presence of TTX. CONCLUSION: Phentermine
      increases brain DA but not 5-HT release in freely moving rats, and TTX reduces,
      but does not fully block this effect. This pattern is similar to that known to be
      produced by d-amphetamine.

PMID- 9578238
TI  - Six-compartment body composition model: inter-method comparisons of total body
      fat measurement.
AB  - OBJECTIVE: To compare 16 currently used total body fat methods to a six
      compartment criterion model based on in vivo neutron activation analysis. DESIGN:
      Observational, inter-method comparison study. SUBJECTS: Twenty-three healthy
      subjects (17 male and 6 female). MEASUREMENTS: Total body water (TBW) was
      measured by tritium dilution; body volume by underwater weighing (UWW); total
      body fat and bone mineral by dual-energy X-ray absorptiometry (DXA), total body
      potassium (TBK) by whole-body 40K counting; total body carbon, nitrogen, calcium,
      phosphorus, sodium and chlorine by in vivo neutron activation analysis;
      skinfolds/circumferences by anthropometry (Anth); and resistance by single
      frequency bioimpedance analysis (BIA). RESULTS: The average of total body fat
      mass measurements by the six-compartment neutron activation model was 19.7+/
      10.2kg (mean+/-s.d.) and comparable estimates by other methods ranged from 17.4
      24.3 kg. Although all 16 methods were highly correlated with the six-compartment
      criterion model, three groups emerged based on their comparative characteristics
      (technical error, coefficient of reliability, Bland-Altman analysis) relative to
      criterion fat estimates, in decreasing order of agreement: 1. multi-compartment
      model methods of Baumgartner (19.5+/-9.9 kg), Heymsfield (19.6+/-9.9 kg),
      Selinger (19.7+/-10.2 kg) and Siri-3C (19.6+/-9.9 kg); 2. DXA (20.0+/-10.8 kg),
      Pace-TBW (18.8+/-10.1 kg), Siri-2C (20.0+/-9.9 kg), and Brozek-UWW (19.4+/-9.2
      kg) methods; and 3. Segal-BIA (17.4+/-7.2 kg), Forbes-TBN (21.8+/-10.5 kg),
      Durnin-Anth (22.1+/-9.5 kg), Forbes-TBK (22.9+/-11.9 kg), and Steinkamp-Anth
      (24.3+/-9.5 kg) methods. CONCLUSION: Relative to criterion fat estimates, body
      composition methods can be organized into three groups based on inter-method
      comparisons including technical error, coefficient of reliability and Bland
      Altman analysis. These initial groupings may prove useful in establishing the
      clinical and research role of the many available fat estimation methods.

PMID- 9578239
TI  - Sagittal diameter in comparison with single slice CT as a predictor of total
      visceral adipose tissue volume.
AB  - BACKGROUND: Abdominal obesity has an important biological and epidemiological
      relationship to disease. The gold standard for measurement of visceral adipose
      tissue (VAT) is assessment by computerized tomography (CT) or magnetic resonance
      imaging (MRI), but because of simplicity and ease in collection, anthropometric
      variables are a desirable alternative to estimate VAT. OBJECTIVE: To compare the
      abilities of a single slice CT scan through the L4-L5 interspace (L4-L5 VAT),
      sagittal diameter, and body mass index (BMI) to estimate total volume VAT. Total
      volume VAT (the gold standard) was measured by total abdominal CT scanning, with
      a mean of 42 CT slices per patient. Estimation of VAT in subjects of similar body
      size was emphasized. DESIGN: Retrospective study of subjects undergoing complete
      abdominal and pelvic CT scanning for clinical reasons. SUBJECTS: 40 subjects (20
      men and 20 women) mean age 56.5y, with a balanced selection for BMI < 27 and >
      27. RESULTS: In univariate regression models, L4-L5 VAT explained the largest
      proportion of the variance in total VAT (R2=0.87 [P<0.001]), though age (R2=0.11
      [P=0.04]), BMI (R2=0.37 [P<0.001]), and sagittal diameter (R2=0.50 [P < 0.001])
      were also statistically significantly related to total VAT. When limited to
      individuals with a BMI > or= 27 however, L4-L5 VAT explained a large proportion
      of the variance in total VAT (R2=0.87 [P < 0.001]) whereas sagittal diameter was
      only of borderline significance (R2=0.20 [P=0.06]), and BMI was not associated
      with total VAT (R2=0.04 [P=NS]). In multiple regression analyses, L4-L5 VAT area
      explained a large proportion of the variance (0.84-0.90), and once in the model,
      BMI, sagittal diameter, and age did not additionally contribute significantly to
      the explained variance in total VAT. CONCLUSIONS: Abdominal sagittal diameter is
      poorly correlated to total VAT for men and women with a BMI > 27. Within a 2 cm
      range of sagittal diameter, there is nearly a three-fold variability in total
      VAT.

PMID- 9578240
TI  - Reduction of sleeping metabolic rate after vertical banded gastroplasty.
AB  - OBJECTIVE: To investigate whether long-term weight loss after vertical banded
      gastroplasty (VBG) results in a sustained reduction of sleeping metabolic rate
      (SMR) as a persistent risk factor for weight regain. DESIGN: Longitudinal
      clinical intervention study of morbidly obese patients undergoing VBG. PATIENTS:
      Group I: Six patients in which body composition and SMR were measured before and
      at 3, 6 and 12 months after VBG. Group II (long-term effect): nine patients in
      which body mass (BM) was measured before VBG, and body composition and SMR were
      measured 98+/-30 months after VBG. MEASUREMENTS: Body composition was assessed by
      deuterium dilution and hydrostatic weighing. SMR was measured (SMRm) in a
      respiration chamber and predicted (SMRp) based on body composition. RESULTS: In
      group I, fat mass and fat free mass decreased significantly after VBG (P < 0.05).
      SMRm decreased from 11.1+/-1.8 (s.d.) MJ/d before VBG to 8.1+/-0.9 MJ/d (P <
      0.05) at 12 months after VBG. In group II at a mean of 98 months after VBG, the
      SMRm (6.9+/-0.7 MJ/d) was lower than the preoperative value of group I (P <
      0.05). SMRm was lower than SMRp at all intervals after VBG (P < 0.05). The ratio
      measured vs predicted SMR was in group I: 1.02+/-0.05 before VBG, 0.91+/-0.08 at
      12 months after VBG (P<0.05), and in group 11: 0.94+/-0.08 at a mean of 98 months
      after VBG (P < 0.05). CONCLUSION: The reduction of SMR adjusted for body
      composition after VBG is sustained as long as weight loss is maintained. The
      sustained and disproportional reduction of SMR may reflect the persistent
      susceptibility of the postobese to weight regain.

PMID- 9578241
TI  - Analysis of the insulin receptor gene tyrosine kinase domain in obese patients
      with hyperandrogenism, insulin resistance and acanthosis nigricans (type C
      insulin resistance).
AB  - OBJECTIVE: To test the hypothesis that the triad of hyperandrogenism, insulin
      resistance and acanthosis nigricans (HAIR-AN syndrome) in the presence of
      obesity, also known as type C insulin resistance (type C), is caused by mutations
      at the tyrosine kinase domain of the insulin receptor gene. DESIGN: A candidate
      gene approach to study the molecular basis for a syndrome of obesity. SUBJECTS:
      15 patients with type C insulin resistance and 25 control individuals.
      MEASUREMENTS: Analysis of polymerase chain reaction (PCR) products of exons 17 to
      21 of the insulin receptor gene, comprising the tyrosine kinase domain, for
      single strand conformational polymorphisms (SSCP) and sequence analysis of exons
      with variant SSCP patterns. RESULTS: A synonymous C to T substitution in position
      3 of codon 984, which does not alter the amino acid predicted, was found in one
      patient and in four of 25 control individuals. CONCLUSION: Type C insulin
      resistance is not commonly caused by mutations in the tyrosine kinase domain of
      the insulin receptor gene.

PMID- 9578242
TI  - Fitness and the effect of exercise training on the dietary intake of healthy
      adolescents.
AB  - OBJECTIVE: In healthy, nonobese, adolescent males and females to: (1) Determine
      the relationship between fitness and energy intake; (2) assess the effect of five
      weeks endurance training on energy intake and food choice and (3) compare food
      record assessments of energy intake with doubly-labeled water (DLW) measurement
      of total energy expenditure (TEE). DESIGN: (1) Cross sectional analysis of
      fitness and food intake and (2) Prospective, randomized, controlled
      interventional study of endurance-type exercise training in 44 females and 44
      males (age range, 15-17 y). MEASUREMENTS: Pre and end interventional three day
      food records were successfully collected from 32 females (15 controls, 17
      trained) and 39 males (19 controls, 20 trained). Fitness was assessed from cycle
      ergometry as peak oxygen uptake normalized both to thigh muscle mass and body
      weight. Thigh muscle mass was measured by magnetic resonance imaging. TEE using
      the DLW technique was measured in 12 females (6 controls, 6 trained) and 20 males
      (10 controls, 10 trained) during weeks 4-5 of the exercise training program
      (simultaneously with the second assessment of food records). Food record data
      were analyzed using the Minnesota Nutrition Data System. RESULTS: Fitness was
      correlated with self reported total caloric intake in males but not females. In
      females, there was a significant increase in fat intake (19.8+/-9%, P < 0.05) and
      a significant decrease in carbohydrate intake (-9.8+/-4%) in the trained
      subjects. No changes were observed in the control subjects. Energy expenditure
      (2072+/-52 kcal/d) was significantly greater than the estimated energy intake
      (1520+/-112 kcal/d, P < 0.007) during the intervention in the trained, but not
      control, subjects. However, there was no weight change in either control or
      trained subjects. In males, no changes were observed in food choice in either
      control or trained subjects. Similar to the females, energy expenditure (2425+/
      22 kcal/d) was significantly greater than the estimated energy intake (2168+/-117
      kcal/d, P < 0.05) during the intervention in the trained, but not control,
      subjects. No weight changes were observed in either group. CONCLUSIONS: Fitness
      is associated with increased self-reported energy intake in males but not
      females, while exercise training led to alterations in food selection (greater
      fat and reduced carbohydrate) only in females. These observations could reflect
      specific gender differences, or, alternatively, the generally lower levels of
      fitness in the females. The apparent negative energy balance without evidence for
      weight loss in both the trained males and females suggests a systematic under
      reporting of food intake during exercise programs in adolescents, and indicates
      the possibility that errors in self reported food intake might be greater during
      transitions from one level of energy expenditure to another.

PMID- 9578243
TI  - Relation of insulin resistance to left ventricular hypertrophy and diastolic
      dysfunction in obesity.
AB  - OBJECTIVE: To assess relations of left ventricular (LV) geometry and function to
      insulin resistance in obesity-a condition associated with volume overload and
      abnormal LV relaxation. DESIGN: Cross-sectional relational study. SUBJECTS: 27
      healthy overweight-obese subjects (18 women, body mass index (BMI) = 35.0+/-4.0
      kg/m2) and 31 age-matched normal-weight controls (21 women, BMI = 22.6+/-2.4
      kg/m2). MEASUREMENTS: Subjects were studied by Doppler-echocardiography the same
      day and hour (08.00 h) as measurements of fasting insulin and blood glucose were
      made. Insulin resistance was determined by the 'Homeostasis Assessment Model'.
      RESULTS: Twelve obese subjects with insulin resistance (IR) had higher body size
      than 15 patients without IR and higher blood pressure than normal-weight controls
      (all P < 0.01). Relative IR was related to isovolumic relaxation time. This
      relation was not maintained after controlling for age, blood pressure, weight and
      height. Isovolumic relaxation time was, however, positively related to diastolic
      blood pressure, a measure of load, in normal controls (r=0.44) and obese without
      IR (r=0.62) but not in insulin resistant subjects (r=0.14). CONCLUSION: IR does
      not independently influence myocardial relaxation in uncomplicated obesity, but
      modulates the effect of load on active diastole.

PMID- 9578244
TI  - Obesity type and clustering of insulin resistance-associated cardiovascular risk
      factors in middle-aged men and women.
AB  - OBJECTIVE: To examine different clusterings of the insulin resistance-associated
      cardiovascular risk factors with respect to different types of obesity. DESIGN: A
      screening programme for obesity (body mass index; BMI> or =30 kg/m2) and
      abdominal adiposity (waist-to-hip ratio; WHR > or = 1.00 in men and > or = 0.88
      in women). SETTINGS: Pieksamaki District Health Centre and the Community Health
      Centre of the City of Tampere, Finland. SUBJECTS: All volunteers were either aged
      36, 41, 46 or 51 y (n=1148) and living in the town of Pieksamaki, with a control
      population of 162 subjects in the City of Tampere. MAIN OUTCOME MEASURES:
      Different clusterings of: 1) hypertension (a systolic blood pressure > or = 160
      mmHg and/or a diastolic blood pressure > or = 95 mmHg or concurrent drug
      treatment for hypertension); 2) hypertriglyceridaemia > or = 1.70 mmol/l; 3) a
      low level of high-density-lipoprotein (HDL) cholesterol; < 1.00 mmol/l in men, <
      1.20 mmol/l in women; 4) abnormal glucose metabolism (impaired glucose tolerance
      or non-insulin-dependent diabetes) and 5) hyperinsulinaemia with a fasting plasma
      insulin > or = 13.0 mU/l. RESULTS: The prevalence of a cluster consisting of
      dyslipidaemia (hypertriglyceridaemia and/or low HDL-cholesterol) and insulin
      resistance (abnormal glucose metabolism and/or hyperinsulinaemia) was found to be
      4% in the control subjects, 18% in the abdominal adipose subjects (WHR > or =
      1.00 in men and > or = 0.88 in women with a BMI < 30 kg/m2), 28% in the 'pure'
      obese subjects (BMI> or = 30 kg/m2 with WHR < 1.00 in men and < 0.88 in women),
      and 46% in the central obese subjects (subjects showing both 'pure' obesity and
      abdominal adiposity). The prevalence rates of the other clusterings of
      abnormalities varied similarly according to the type of obesity. CONCLUSION:
      Clusterings of insulin resistance-associated abnormalities were related to the
      type of obesity in both middle-aged men and middle-aged women.

PMID- 9578245
TI  - Is obesity contagious?

PMID- 9578246
TI  - W64R mutation in beta-3-adrenergic receptor gene and weight in a large population
      sample.
AB  - We have investigated the W64R (Trp64Arg) mutation in the beta-3-adrenergic
      receptor in 2270 healthy British males aged 50-61 y. The frequency of the rare R
      allele was 0.07 (95% confidence interval (CI) 0.06-0.08). The men showed an
      absence of association between W64R genotype and weight or height, both in the
      whole sample and in each quintile of the body mass index (BMI), and there was no
      association with tendency to gain weight. The W64R heterozygous state appears not
      to be a major contributing factor to obesity in the general population.

PMID- 9578247
TI  - BAOMS scientific meetings: the pattern for the future. British Association of
      Oral and Maxillofacial Surgeons.

PMID- 9578248
TI  - The BAOMS United Kingdom survey of facial injuries part 1: aetiology and the
      association with alcohol consumption. British Association of Oral and
      Maxillofacial Surgeons.
AB  - OBJECTIVE: To determine the age and sex distribution, timing, causes,
      geographical location, and nature of facial injuries in the UK and to determine
      the association of these factors with alcohol consumption by the patient or any
      other involved person. DESIGN: A 12-section proforma was completed on all
      patients with facial injuries covering their age and sex, time and day of injury
      and presentation, the cause and type of injury and where it occurred, the
      treatment the patient received, any other injuries, and alcohol consumption by
      the patient and any other involved person. The total attendances for the study
      week and the catchment population for each A&E department were recorded. SETTING:
      163 of the A&E departments in the UK served by 137 of the UK's oral and
      maxillofacial departments. SUBJECTS: All patients who presented with facial
      injuries to these 163 A&E departments in England, Scotland, Wales and Northern
      Ireland over the study week from 09.00 hours on Friday 12 September 1997 to 08.59
      hours on Friday 19th September 1997. RESULTS: 6114 patients with facial injuries
      presented over the week, out of a total of 152,692 A&E attendances. The
      male:female ratio was 68:32. This rose to 79:21 in assault cases. The mean age of
      all patients was 25.3 years, of males 23.2 years, and of females 29.8 years.
      Forty per cent of the facial injuries were caused by falls. A large proportion of
      these happened to the under-5 age group in the home. Eleven per cent of all falls
      were associated with alcohol consumption. Twenty-four per cent of the facial
      injuries were caused by assault. The commonest sites for assault were the street
      followed by public drinking establishments. More women than men were assaulted at
      home. Fifty-five per cent of assaults were related to alcohol consumption. Eight
      per cent of assaults were with bottles or glasses. Five per cent of the facial
      injuries occurred in road traffic accidents (RTAs). Fifteen per cent of RTA
      victims had consumed alcohol. The 15-25 age group suffered the greatest number of
      facial injuries caused by assault and RTAs and had the highest number associated
      with alcohol consumption. At least 22% of all the facial injuries in all age
      groups were related to alcohol consumption within 4 hours of the injury. In the
      over 15 age groups, alcohol consumption was associated with 90% of facial
      injuries occurring in bars, 45% on the street, and 25% in the home. Assault, RTA
      and alcohol consumption conveyed an increased risk of serious facial injury.
      CONCLUSIONS: Campaigns should be instituted to educate young people about the
      link between excessive alcohol consumption, assault, road traffic accidents and
      serious facial injury.

PMID- 9578249
TI  - UK National Third Molar project: the initial report.
AB  - The National Third Molar (NTM) project was set up to assess current clinical
      practice in the UK concerning the management of third molar teeth. Patients were
      recruited from both hospital and general dental practice. During the one month
      study period 9248 patients with 26,577 third molars were recruited. In this
      report we present the findings in the 8298 patients with 25,001 third molars who
      were referred to hospital for assessment. Over half of all patients referred for
      assessment had either no extractions or a single third molar extracted. Less than
      a quarter of all patients referred underwent removal of all four third molars.
      Twenty per cent of all third molars assessed were not extracted. Of all lower
      third molars listed for extraction, 9574 (78%) were associated with symptoms or
      disease. Pericoronitis was the commonest indication for extraction and was cited
      in 39.5% of all extractions. Almost 70% of third molar extractions were done
      under general anaesthesia while less than a quarter were performed under local
      anaesthesia alone.

PMID- 9578250
TI  - Two methods of administration of propofol for dental sedation.
AB  - Propofol was used for intravenous sedation in a group of 19 healthy fit young
      patients undergoing third molar extractions. We compared two ways of giving the
      drug, patient-controlled and operator-controlled, in a crossover trial. There
      were no differences between the two methods. The psychomotor functions returned
      to normal by 60 min, there was a high incidence of partial or complete amnesia
      and both methods were acceptable to 18/19 patients. There were only minimal
      changes in the respiratory function, and oxygen saturation remained normal. The
      only problem noted was mild pain on injection in 4 patients.

PMID- 9578251
TI  - Transient contralateral hypoglossal nerve palsy following third molar surgery
      under day-case general anaesthesia: a case report and review of the literature.
AB  - This paper presents the first documented case of hypoglossal nerve palsy
      subsequent to an oral surgical technique under day stay endotracheal general
      anaesthesia and discusses diagnosis, management, aetiology and implications for
      clinicians.

PMID- 9578252
TI  - An assessment of patients' attitudes to day-case general anaesthesia for removal
      of mandibular third molars.
AB  - Day-case surgery is used extensively in many hospital departments including
      departments of oral surgery. In this study, the preoperative attitudes of 170
      patients to, and postoperative satisfaction with, surgical removal of third molar
      teeth under general anaesthesia as day cases were evaluated. A 69% response to
      the questionnaire (n = 110) indicated that 102 (96%) of the 106 that had been
      satisfactorily completed were satisfied with the prospect of afternoon, day-case
      removal of their third molar teeth, and 96 (91%) remained satisfied
      postoperatively. Only two patients did not like the idea beforehand and had their
      opinions confirmed. Patients' comments included satisfaction with the support
      they received (n = 29) and with pain control (n = 5) and amount of information
      given (n = 5). However, five complained of the long wait and two who were last on
      the list thought that they should have been kept in overnight.

PMID- 9578253
TI  - Outcome of arthroscopic surgery to the temporomandibular joint correlates with
      stage of internal derangement: five-year follow-up study.
AB  - We studied the 5-year long-term outcome of arthroscopic surgery, and also
      investigated whether outcome correlates with stage of internal derangement of the
      temporomandibular joint (TMJ). A consecutive group of 41 patients (56 joints) who
      had been followed up for between 3 and 5 years were involved in this study. The
      result was excellent in 22 patients (54%) and fair in 15 (37%). 7/14 were
      excellent and 5/14 were fair in stage III, 7/12 were excellent and 4/12 were fair
      in stage IV, and 8/15 were excellent and 6/15 were fair in stage V. Arthroscopic
      surgery of the TMJ is an effective and minimally invasive technique for various
      stages of internal derangement.

PMID- 9578255
TI  - An experimental study on the aspirating reliability of different types of
      injection syringes with regard to the formation of punch cylinders.
AB  - Aspiration before local anaesthesia is essential to avoid an incorrectly placed
      needle. We tested 142 types of cannula in mucobuccal preparations from 29
      cadavers. The cannulas were obtained from 23 different firms and the formation of
      punch cylinders caused by injection was studied at angles of penetration of 70
      degrees and 90 degrees. The force of puncture was measured by a computer
      controlled apparatus. In a second series of tests the aspirating ability of 121
      cannulas with self-aspirating and actively aspirating syringes was tested in
      vitro. The results show that false negative aspirations are caused by: using a
      cannula that is too small (<= 27 Gauge); the cannula lumen becoming clogged with
      tissue punch cylinders; using a Carpule needle end that is too short to perforate
      the rubber of the ampoule; containing rubber fragments in the back of the Carpule
      needle end; and using an injection syringe with too small a viewport when the
      injection syringe was positioned at a 90 degrees. We recommend the construction
      of a system in which the distance between the cone and viewport is reduced.

PMID- 9578254
TI  - Intra-articular injection of hyaluronic acid reduces total amounts of leukotriene
      C4, 6-keto-prostaglandin F1alpha, prostaglandin F2alpha and interleukin-1beta in
      synovial fluid of patients with internal derangement in disorders of the
      temporomandibular joint.
AB  - This prospective randomised study was designed to assess the effect of an intra
      articular injection of sodium hyarulonate on internal derangement in disorders of
      the temporomandibular joint. Fifteen patients (4 men, 11 women, mean (SEM) age
      33(3) years) with unilateral internal derangement of the temporomandibular joint
      without radiographic evidence of the condylar degeneration who were randomly
      allocated to have arachidonic acid metabolites (n = 9) or cytokines (n = 6)
      measured in synovial fluid. The preauricular area was disinfected and
      anaesthetised locally with 1% lignocaine hydrochloride. Synovial fluid was
      collected by rinsing the joint with saline 5 ml. Sodium hyaluronate 1 ml (10 mg)
      was then injected into the superior compartment of the temporomandibular joint.
      The treatment was repeated after two weeks. The effects of sodium hyaluronate on
      total amounts of arachidonic acid metabolites and cytokines and on symptoms was
      measured. Injection of sodium hyaluronate caused significant reductions in the
      mean (SEM) of total amounts of leukotriene C4 (4.68 (2.27) to 0.48 (0.24)
      ng/joint), 6-keto-prostaglandin F1alpha (12.12 (2.78) to 5.19 (1.90) ng/joint),
      prostaglandin F2alpha (12.63 (5.51) to 4.21 (2.20) ng/joint), and interleukin
      1beta (100.5 (14.2) to 50.8 (13.9) pg/joint), respectively (P<0.05 in each case).
      The mean (SEM) pain score was significantly reduced from 2.56 (0.18) to 0.89
      (0.26) (P<0.01), the noise score from 2.18 (0.23) to 1.18 (0.18) (P<0.05), and
      degree of mouth opening from 28.2 (2.5) to 34.9 (2.0) mm (P<0.01). However, no
      improvement in symptoms was recorded in 1/9, 5/11, and 1/9 patients,
      respectively. These findings suggest that inflammation plays a part in internal
      derangement of the temporomandibular joint, and injection of an anti-inflammatory
      substance may be beneficial to such patients.

PMID- 9578256
TI  - A one-year review of maxillofacial sports injuries treated at an accident and
      emergency department.
AB  - To assess the aetiology and demand for oral and maxillofacial surgery services
      associated with sports injuries, a prospective study was undertaken. Data were
      collected from consecutive patients (with maxillofacial injuries associated with
      sports) attending the accident and emergency department at the Cardiff Royal
      Infirmary in the UK during a 12-month period and analysed. Data relating to
      demography, aetiology, site and extent of injury, treatment and outcome were
      collected. There were 790 attendances (695M:85F) arising principally from
      injuries related to rugby (n = 206), cycling (n = 189) and football (n = 109) but
      few from recognized contact sports (n = 26). The principal causes of these
      injuries were direct bodily contact (n = 260) and falls (n = 219). The commonest
      injury was soft-tissue laceration (n = 604); 80 patients had dentoalveolar
      fractures and 64 patients had fractures of the facial skeleton. Injuries were
      located in the upper- (n = 257), middle- (n = 201) and lower third of the face (n
      = 124) with 188 lip/intraoral injuries. Repair of lacerations (n = 600) was the
      commonest treatment; only 46 fractures required interventive treatment. Follow-up
      was performed for most of these patients at the Department of Oral and
      Maxillofacial Surgery at the Dental Hospital (n = 404) and general medical/dental
      practitioners (n = 258). These data highlight the importance of oral and
      maxillofacial surgery staff in the management of sports injuries in accident and
      emergency departments. Moreover, they suggest the need for prioritization of rule
      and legislation changes and the continuing need to improve safety standards to
      prevent maxillofacial injuries.

PMID- 9578257
TI  - Recurrent pleomorphic adenomas of the parotid gland: clinical evaluation and long
      term follow-up.
AB  - We report 94 patients with recurrent pleomorphic adenomas of the parotid gland
      who were referred to our clinics after operations elsewhere. In 78 patients (83%)
      enucleation was the surgical technique used to remove the tumour. Patients with
      more than one recurrence were significantly younger than patients who had only
      one. Many recurrent adenomas (44%) were multifocal. In 20 (21%) further
      recurrences became obvious after we had operated on them. The mean time interval
      before recurrence ranged from 7.3 to 10.1 years. Twenty patients (14%) had
      persistent motor disorders of the facial nerve after operation for recurrence (n
      = 143). Twenty eight of the 84 patients from whom follow-up data could be
      obtained developed Frey's syndrome (33%). Our data support the importance of an
      adequate initial operation to avoid recurrences of pleomorphic adenomas in the
      parotid gland.

PMID- 9578258
TI  - Extraglandular Warthin's tumours: clinical evaluation and long-term follow-up.
AB  - Nine patients with extraglandular cystadenolymphoma (Warthin's tumour) were
      treated between 1965 and 1995 at the Department of Otorhinolaryngology,
      University of Gottingen. This number corresponds to 2.7% of all Warthin's tumours
      treated at our clinic so far. Although this rare tumour is well documented by
      case reports, a controlled follow-up study has not yet been published to the best
      of our knowledge. The retrospective investigation presented here gives the
      patients' clinical data and documents therapeutic success. Our results show the
      complete absence of recurrences after surgical excision of extraglandular
      cystadenolymphomas.

PMID- 9578259
TI  - Metastases to parotid gland from cancers of the upper airway and digestive tract.
AB  - Forty-four cases of parotid metastases were diagnosed and treated in the period
      1968-1994. In 10 patients (23%), the primary tumour was sited in the mucosal
      layer of the upper airway or digestive tract: oropharynx (n=3), larynx (n=3),
      nasopharynx (n=2), hypopharynx (n=1) and the maxillary sinus (n=1).
      Histologically, the primary tumour was squamous cell carcinoma in 9 cases and
      adenocarcinoma in one. One patient received surgical treatment only, two patients
      surgery and postoperative radiotherapy, one radiotherapy only, four chemotherapy
      and two symptomatic treatment only. Only one patient is alive, disease-free, 5
      years after treatment. The other patients died: six within 1 year, two within 2
      years and one within 3 years of diagnosis.

PMID- 9578260
TI  - The incidence of other primary tumours in patients with oral cancer in Scotland.
AB  - OBJECTIVE: To find out the incidence of second or multiple primary malignant
      tumours in patients with oral cancer in Scotland and identify the sites at most
      risk. DESIGN: Retrospective cohort study of data from the Cancer Registry.
      SUBJECTS: 1891 patients registered with oral cancer in Scotland between 1 January
      1980 and 31 December 1986. MAIN OUTCOME MEASURES: Relative risks of subsequent
      cancers in patients with oral cancer. Identification of the sites at most risk of
      second cancers. RESULTS: Of the 1891 patients, 228 (12%) developed a second
      primary cancer. The mean follow-up period was 3.2 years. Fourteen patients had 3,
      and 2 patients had 4 primary cancers. The overall risk of second primary cancers
      was 2.03 (95% confidence intervals (CI) 1.77 to 2.39) times greater than expected
      in the general population. The relative risk for male patients was 1.95 (95% CI
      1.65 to 2.24) and for female patients 2.29 (95% CI 1.7 to 2.9). CONCLUSIONS: Men
      with cancer of the lip in Scotland have an increased risk of developing second
      cancers of the lip and skin (excluding melanoma), whilst women with cancer of the
      lip have an increased risk of developing skin cancer only. Both men and women
      with intra-oral cancers have increased risks of developing second cancers of the
      oral cavity, pharynx, and trachea, bronchus, and lung, while men alone have an
      increased risk of developing second cancers in the oesophagus.

PMID- 9578262
TI  - Correction of post-traumatic asymmetry by mandibular angle reduction: report of
      two cases.
AB  - We present two patients with post-traumatic mandibular asymmetry, caused by
      flaring of a fragment containing the mandibular angle in between two fractures.
      No occlusal disturbance was evident in either case. Instead of refracturing or
      ramus osteotomies, the asymmetry was corrected by transoral ostectomy of the
      mandibular angle with good aesthetic results.

PMID- 9578261
TI  - An audit of oral and dental health regimens practised in the management of
      oropharyngeal cancer.
AB  - The purpose of the present study was to find out what preventive care was offered
      to patients after radiotherapy, particularly if they were dentate. As the mean
      age of the population increases and the number of people who retain at least some
      of their teeth into old age also rises, it is likely that more and more people
      with a diagnosis of oral cancer will be dentate. The incidence of oropharyngeal
      cancer has also started to increase recently and is affecting more young and
      dentate people. It is of paramount importance to provide comprehensive management
      for these patients, not only to remove the disease and reconstruct the defect,
      but also to provide the patient with the opportunity of experiencing a good
      quality of life by having a comfortable mouth after treatment. A questionnaire
      was sent to all senior fellows of the British Association of Oral and
      Maxillofacial Surgeons (BAOMS) and the results analyzed. The results of this
      survey show that improvements could be made if some simple preventive measures
      were instigated in the early stages of treatment.

PMID- 9578263
TI  - Antibiotic prescribing in third molar surgery.

PMID- 9578264
TI  - General medical practitioners' knowledge of the specialty of oral and
      maxillofacial surgery.

PMID- 9578265
TI  - Traumatic myositis ossificans of the temporal and masseter muscle.

PMID- 9578266
TI  - The postcoital test: a controversial investigation.

PMID- 9578267
TI  - Mammalian follicle-stimulating hormone receptors and their ligands.

PMID- 9578268
TI  - Compression stimuli increase the efficacy of breast pump function.
AB  - OBJECTIVE: The dynamics of milk ejection and also prolactin concentration in the
      blood during milk expression by means of a breast pump were studied in 82
      lactating women. STUDY DESIGN: The design of the breast pump used in this study
      is new. It is based on the correlation with the amplitude, duration and frequency
      of vacuum and compression stimuli formed by the baby's mouth apparatus during the
      suckling process. RESULTS: It was found that during continuous co-action of the
      vacuum and compression stimuli at a frequency of 1 cycle per second, the rate of
      milk ejection from the breast changed periodically. The highest rates of milk
      ejection coincided with the greatest rises in intramammary pressure. When the
      compression stimulus was turned off, leaving only the vacuum, the period of the
      first rise in pressure increased 1.5-2 fold, with a 1.5-2 fold reduction in the
      milk ejection rate as compared with the normal function of the breast pump. The
      basal prolactin level on day 3 and 5 post delivery in women who used a breast
      pump was not significantly different from that of puerperal women who only breast
      fed their babies. Prolactin concentration in the blood of puerperal women did not
      change within the 5-6 min of expression and stimulation with the breast pump. The
      prolactin level began to increase by the 10th minute, whereas by the 25th minute
      it exceeded the initial concentration 1.3-1.5-fold. CONCLUSION: It is suggested
      that by introducing a tactile component to the mechanism of the breast pump, milk
      secretion is enhanced, as well as stimulating the breast milk flow. This directly
      improves the dynamics of breast milk expression.

PMID- 9578269
TI  - Local collagen turnover in human foetal membranes during full term vaginal
      delivery.
AB  - OBJECTIVES: To investigate if changes in local metabolism of collagens type I and
      type III may contribute to the term rupture of the foetal membranes. STUDY
      DESIGN: In extracts from membranes taken along the rupture line and near the site
      of the umbilical cord attachment to the placenta, we measured concentrations of
      specific markers of collagen synthesis, namely C-terminal propeptide of type I
      collagen (PICP) and N-terminal propeptide of type III collagen (PIIINP), as well
      as the concentration of the pyridinoline cross-linked C-terminal telopeptide of
      type I collagen (ICTP), which reflects the rate of collagen type I breakdown.
      RESULTS: The mean concentrations of PICP and PIIINP did not differ statistically
      between the two examined groups of samples. The mean ICTP concentration was
      threefold higher in extracts prepared from samples taken near the rupture site,
      than from membranes derived from the proximity of the umbilical cord attachment.
      CONCLUSIONS: Term rupture of foetal membranes is accompanied by increased local
      degradation of type I collagen fibrils at the rupture site, whereas the
      biosynthesis of collagen types I and III remains unchanged.

PMID- 9578270
TI  - Lone hyperuricemia during pregnancy: maternal and fetal outcomes.
AB  - OBJECTIVE: Study of maternal and fetal consequences of lone hyperuricemia during
      pregnancy and demonstration that lone hyperuricemia is not a risk factor
      regarding the onset of preeclampsia. STUDY DESIGN: Retrospective study of two
      groups of women, one found to have lone hyperuricemia during pregnancy (n=102)
      and the others with normal serum uric acid levels (n=100). RESULTS: The only
      consequence identified of the lone hyperuricemia was a lower birth weight of
      children born to mothers found to have lone hyperuricemia for more than 2 weeks
      (P<0.05). CONCLUSIONS: Lone hyperuricemia is not a risk factor regarding the
      onset of preeclampsia. It is therefore unnecessary to measure serum uric acid
      level during a normal pregnancy.

PMID- 9578271
TI  - Preeclampsia, preterm delivery and infant cerebral palsy.
AB  - OBJECTIVE: To evaluate the association between preeclampsia and cerebral palsy
      among preterm infants. STUDY DESIGN: A cohort study of 345 singleton preterm (24
      to 33 weeks gestation) infants delivered at an institution where no mothers
      received magnesium sulphate. We investigated the relationship of preeclampsia to
      the development of infant cerebral palsy (spastic quadriplegia, hemiplegia or
      diplegia) at two years' corrected age. Potential confounders were controlled for
      by politomous logistic regression analysis. RESULTS: The prevalence of cerebral
      palsy in surviving infants from normotensive and preeclamptic pregnancies was
      13.4% (38/284) and 3.3% (2/61), respectively (P=0.026 by Fisher exact test).
      After control for potential confounders (gestational age, infant gender,
      birthweight standard deviation score, mode of delivery), the likelihood of infant
      cerebral palsy was reduced by preeclampsia (odds ratio 0.16, 95% confidence
      interval=0.04-0.74 for infants from preeclamptic versus normotensive pregnancies
      being palsied). CONCLUSION: Among preterm infants, the protective effect of
      preeclampsia against cerebral palsy is manifest in the absence of magnesium
      sulphate utilization.

PMID- 9578272
TI  - Isolated hydramnios at term gestation and the occurrence of peripartum
      complications.
AB  - OBJECTIVE: To determine if hydramnios at term gestation is an independent risk
      factor for poor pregnancy outcome and perinatal death. STUDY DESIGN: The study
      population consisted of 60,702 patients with singleton gestation who delivered at
      term (>37 weeks). Patients were classified into two groups according to the
      presence or the absence of hydramnios. Hydramnios was diagnosed in the presence
      of an amniotic fluid index greater than 25 cm or of a maximum vertical pocket of
      amniotic fluid of at least 8 cm or by subjective assessment. Logistic regression
      analysis was used to evaluate the unique contribution of hydramnios to fetal
      death and to perinatal and maternal morbidity. RESULTS: The prevalence of
      hydramnios was 1211/60,702 (2%). Patients with hydramnios had a higher incidence
      of complications than those with a normal amount of amniotic fluid: cesarean
      section (22.8 vs. 8.5%, P<0.01), antepartum death (0.6 vs. 0.2%, P<0.005),
      postpartum death (2.8 vs. 0.4%, P<0.01), abruptio placenta (0.9 vs. 0.3%,
      P<0.001), fetal distress (6.1 vs. 3.65%, P<0.0015), meconium-stained amniotic
      fluid (17.8 vs. 15%, P<0.001), low Apgar score at 5 min (2.95 vs. 1%, P<0.01),
      malpresentation (6.8 vs. 2.9%, P<0.01), clinical chorioamnionitis (0.3 vs. 0.1%,
      P<0.05), prolapse of cord (2.2 vs. 0.3%, P<0.01), and large-for-gestational-age
      infant (LGA) (23.8 vs. 8.1%, P<0.01). When adjusted for confounding variables,
      the presence of hydramnios remained strongly associated with perinatal mortality
      (odds ratio 5.5 (95% CI 3.2-9.3)) and neonatal and maternal morbidity (odds
      ratios 2.1 (CI 1.1-3.7) and 2.3 (CI 1.9-2.7), respectively). CONCLUSIONS: (1)
      Hydramnios at term is an independent risk factor for perinatal death; (2) Fetal
      surveillance is warranted in patients with hydramnios even in the absence of
      other known risk factors for adverse pregnancy outcome.

PMID- 9578273
TI  - Pregnancy outcome in women with beta-thalassemia major and HIV infection.
AB  - OBJECTIVES: To conduct a study of maternal and foetal outcome in pregnant
      transfusion-dependent beta-thalassemia major (beta-TM) women with HIV-1 disease.
      STUDY DESIGN: The course and outcome of pregnancy was studied prospectively in
      123 women with transfusion-dependent beta-thalassemia major, of which 81 were HIV
      1 positive, at Sanjay Gandhi hospital Manipur, India, from January 1990 to
      January 1997. The clinical and immunological status of the seropositive women was
      compared with matched seronegative thalassemic control groups. RESULTS: Over a
      period of 7 years, 123 women with beta-TM conceived. One hundred and eleven (90%)
      conceptions were spontaneous including the 81 HIV-1 positive women and 12 (10%)
      conceptions occurred after induction of ovulation. Among these 81 patients the
      following stages of HIV-1 infection were represented: 39 C2 stage (AIDS indicator
      conditions); 42 A2 stage (asymptomatic) (CDC 1993). Of these 39 women, 12/39
      (31%) underwent medical termination of pregnancy (MTP) by 8 weeks gestation and
      five (13%) died undelivered by 32 weeks gestation due to fulminating pneumocystis
      carinii pneumonia. There were 80/123 (65%) singleton vaginal deliveries of which
      22/80 (28%) were preterm and 58 (71%) term. All 22 preterm births occurred in
      mothers with aids indicator conditions, were vaginal deliveries, and they had
      positive viral cultures for HIV-1 within one week of birth. Ten of these neonates
      died by 8 weeks of AIDS and the remaining 12 died of AIDS indicator disease by 15
      months of age. At term a significant 25% (31/123) of women delivered by elective
      caesarean section due to cephalopelvic disproportion. Except for those inflicted
      with AIDS, the remaining women remained well throughout pregnancy. CONCLUSION:
      Successful outcome of pregnancies does occur in women with beta-TM and also in
      those with asymptomatic HIV disease. Associated AIDS indicator conditions cause
      appreciable perinatal and maternal morbidity and mortality.

PMID- 9578274
TI  - A randomized comparison of nifedipine and ritodrine for suppression of preterm
      labor.
AB  - OBJECTIVES: To compare the efficacy and safety of nifedipine and ritodrine in
      preventing preterm labor, and to evaluate maternal side effects and neonatal
      outcome. STUDY DESIGN: Non-blind, randomized controlled trial RESULTS: A
      randomized trial of 102 pregnant women with gestational ages under 34 weeks,
      including 24 with twin pregnancies and 45 on betasympathicomimetic drugs, who had
      regular uterine contractions with either observed cervical changes or preterm
      rupture of membranes. After stratification women were randomly assigned to
      receive either ritodrine intravenously or nifedipine orally. Fifty-five women
      were randomized to the nifedipine group and 47 to the ritodrine group. As
      expected, both groups were comparable in terms of several entry variables,
      including mean gestational age, ruptured membranes, treatment with tocolytic
      drugs, cervical examination, contraction frequency, age, and twin gestation.
      Delivery of women in the nifedipine group was delayed for 48 h, 7 days, and until
      34 weeks gestation in 33 (60%), 26 (47%) and 21(38%) cases, respectively,
      compared with 31 (66%), 21(45%) and 11(23%) women in the ritodrine group (no
      significant difference). Maternal side effects were significantly less common in
      the nifedipine group than in the ritodrine group, however after 7 days of therapy
      there was no difference between the two groups. Neonatal outcome was similar in
      the two groups, with four neonatal deaths in the nifedipine and five in the
      ritodrine group. CONCLUSIONS: Nifedipine seems to be as effective as ritodrine in
      the treatment of preterm labor and is associated with less frequent side effects.

PMID- 9578275
TI  - The role of deoxyribonuclease I in amniotic fluid during pregnancy and labour.
AB  - The purpose of this study was to detect the presence, and determine the normal
      values and the significance of DNase I in the amniotic fluid and in human
      placentas. Fifty-one pregnant women at 16-22 weeks of gestation and 89 women in
      spontaneous labour at term were recruited to the study. DNase I activity was
      measured in amniotic fluid and cytoplasmic extracts from the fetal portion of
      placentas by using a spectrophotometric technique (DNA precipitation assay) and
      nucleic acid electrophoresis, following degradation of the DNA by the enzyme.
      DNase I activity was undetectable in the placental cytoplasmic extracts. In the
      second trimester of pregnancy DNase I activity was detectable in amniotic fluid
      (2.3+/-0.64x10(5) U/l). During labour DNase I activity was also detectable, but
      reduced levels were observed in the presence of clear amniotic fluid, compared to
      second trimester levels, (1.9+/-0.44x10(5) U/l, P<0.001), whereas higher levels
      were found in the presence of meconium-stained amniotic fluid compared to both
      second trimester and clear amniotic fluid at labour (11.4+/-4.1x10(5) U/l,
      P<0.001 and P<0.001, respectively). Three out of 17 fetuses with meconium-stained
      amniotic fluid (18%) developed perinatal infection. In conclusion, the detection
      of DNase I activity in the amniotic fluid of second and third trimester indicates
      a physiological role in human pregnancy. DNase I activity normally decreases at
      term, compared to second trimester levels, but increases significantly in the
      presence of meconium.

PMID- 9578276
TI  - Ascending dose tolerance study of intramuscular carbetocin administered after
      normal vaginal birth.
AB  - OBJECTIVE: To determine the maximum tolerated dose (MTD) of carbetocin (a long
      acting synthetic analogue of oxytocin), when administered immediately after
      vaginal delivery at term. MATERIALS AND METHODS: Carbetocin was given as an
      intramuscular injection immediately after the birth of the infant in 45 healthy
      women with normal singleton pregnancies who delivered vaginally at term. Dosage
      groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were
      assigned to blocks of three women according to the continual reassessment method
      (CRM). RESULTS: All dosage groups consisted of three women, except those with 100
      microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events:
      hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and
      retained placenta (four). Serious adverse events occurred in seven women: six
      cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five
      cases of additional oxytocics administration and five cases of blood transfusion.
      Maximum blood loss was greatest at the upper and lower dose levels, and lowest in
      the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000
      ml occurred in the 200 microg group. The majority of additional administration of
      oxytocics (4/5) and blood transfusion (3/5) occurred in the dose groups of 200
      microg. All retained placentae were found in the group of 200 microg. CONCLUSION:
      The MTD was calculated to be at 200 microg carbetocin.

PMID- 9578277
TI  - Twin gestation: is there a correlation between the location of the gestational
      sacs at the beginning of pregnancy, and the order of delivery.
AB  - OBJECTIVES: To determine whether there is a dynamic in the location of amniotic
      sacs in a twin gestation, during pregnancy. STUDY DESIGN: The study group
      comprised 63 twin pairs discordant for sex, who by vaginal sonography performed
      between 14 and 16 weeks' gestation, were characterized as first twin (opposite
      the internal os), and second twin. The order of delivery was recorded in the
      pregnancies that ended with vaginal birth. RESULTS: Thirty seven of 41 (90.2%)
      twins who were delivered vaginally (between 32 and 41 weeks' gestation), were
      born in the same order as that predicted by transvaginal sonography early in
      pregnancy. It was found that in this small series there was a dynamic in the
      amniotic sac location in twin gestations during pregnancy in only about 10% of
      the cases. CONCLUSIONS: In roughly 90% of twins, there is no dynamic in the
      location of the amniotic sacs during pregnancy, and the first twin at the
      beginning of pregnancy intrinsically remains.

PMID- 9578278
TI  - Health services effects of a reduced routine programme for antenatal care. An
      area-based study.
AB  - OBJECTIVE: To assess the consequences of a reduction of the routine programme for
      surveillance of normal pregnancy. STUDY DESIGN: An area-based study of a total
      pregnant population comparing utilization of care the years before and after a
      new routine antenatal programme was introduced, a reduction of three to four
      midwife visits during the second half of pregnancy. All women from the catchment
      area who gave birth in 1990 (n=2008) and 1992 (n=1874) and had attended antenatal
      care in the area during the second half of their pregnancy, were analyzed for use
      of prenatal primary and secondary care, obstetric interventions, pregnancy
      outcome and perinatal outcome. RESULT: Compliance to the programme improved,
      resulting in a reduction of only 1.8 visits per pregnancy. Extra visits initiated
      by staff increased slightly, but extra contacts initiated by the mother remained
      very few. There were no significant differences in maternal outcome or obstetric
      interventions and the rates of prematurity, low birthweight, low Apgar score and
      the need for neonatal interventions were equal both years. CONCLUSION: This
      reduction of three to four scheduled visits in the traditional antenatal care
      programme can be done without increasing demands for extra visits, need for
      specialist consultations or emergencies or less favourable outcome.

PMID- 9578279
TI  - Diabetes insipidus, Sheehan's syndrome and pregnancy.
AB  - OBJECTIVE: To study the role of vasopressin in osmoregulation in two successive
      pregnancies in a woman with Sheehan's syndrome. STUDY DESIGN: Diabetes insipidus
      (DI) became manifest during two pregnancies in a woman with postpartum
      hypopituitarism. RESULTS: Water deprivation-vasopressin administration tests
      demonstrated partial central DI, corrected with vasopressin in week 12, but only
      with desmopressin in the third trimester, when placental cystylamino peptidase
      (vasopressinase) contributes to the severity of the DI. CONCLUSION: If DI occurs
      during pregnancy it may be the first manifestation of a latent central DI, which
      is often idiopathic, but rarely the first symptom of a pituitary or hypothalamic
      abnormality. It may also be part of Sheehan's syndrome.

PMID- 9578280
TI  - Prenatal diethylstilbestrol exposure and self-reported immune-related diseases.
AB  - OBJECTIVE: To compare self-reports of immune-related diseases in
      diethylstilbestrol (DES) daughters and controls. Prenatal exposure to DES has
      been associated with several malformations in the lower genital tract, a higher
      prevalence of adenosis, and increased risk of clear cell adenocarcinoma, and
      estrogen-dependent tumors. Lately, reports have been published indicating a link
      between DES exposure and alterations in the immune system. The present study
      focuses on the possible clinical consequences of an affected immune system. STUDY
      DESIGN: DES daughters (n=170) and control women (n=123) completed questionnaires
      containing lists of immune-related diseases, specified into three categories (i)
      allergies, (ii) auto-immune disorders, and (iii) infectious diseases. RESULTS:
      DES daughters reported significantly more disease conditions than the controls.
      Analyses for separate disease categories (allergies, auto-immune disorders,
      infectious disease), yielded a statistically significant difference only for
      infectious disease. Within this last category, two infectious diseases yielded
      highly significant differences: bladder infection and measles. CONCLUSION: The
      present findings suggest that DES daughters are at higher risk of developing
      immune-related disease states.

PMID- 9578281
TI  - Mapping of androgen, estrogen and progesterone receptors in the anal continence
      organ.
AB  - OBJECTIVE: To investigate the expression of androgen, estrogen and progesterone
      receptors (ARs, ERs, PRs) in the tissues of the anal continence organ using
      immunohistochemical techniques. STUDY DESIGN: Thirty-nine samples of anorectal
      tissue were obtained from 23 patients (seven men, seven premenopausal women and
      nine postmenopausal women). Immunostaining for ARs, ERs and PRs was performed by
      the ABC technique using 3,3'-diaminobenzidine tetrahydrochloride as the
      chromogen. RESULTS: Specific immunostaining for ARs, ERs and PRs was found
      exclusively over cell nuclei. ARs were found in the smooth muscle cells of the
      internal anal sphincter in all but one of the females (10/11) and all males
      (7/7), ERs were found in 12/12 females and 4/7 males, and PRs were found in 4/10
      females and 1/7 males. The squamous epithelium exhibited a similar pattern of
      immunostaining. The nuclei of the striated muscle fibers expressed none of the
      sex steroid receptors investigated. CONCLUSION: The intense expression of ARs,
      ERs and, in some cases, PRs in the tissues of the anal continence organ at all
      ages and in both sexes indicates that this organ is a target for sex steroid
      hormones.

PMID- 9578282
TI  - Obesity in obstetrics and gynaecology.
AB  - In some countries, the incidence of obesity doubles every 10 years. For the
      obstetrician-gynecologist, there are many different situations where the
      patient's excess body weight calls for an adapted diagnostic and therapeutic
      approach. Obesity does not in itself appear to be a factor lowering fertility.
      However obesity-induced hormone disorders could contribute, in certain cases, to
      biological imbalance and thus favor the development of ovulation dysfunction.
      Pregnancy in obese women should be managed as a high risk pregnancy. The
      incidence of gestational diabetes and hypertension is increased. Macrosomatia is
      frequent. There is a 2- to 3-fold increase in the rate of cesarean sections with
      more complications. Fetal morbidity does not appear to be changed when maternal
      weight gain is limited. With obesity, there is an increased risk for breast and
      endometrial cancer due, for most authors, to elevated levels of circulating
      estrogens resulting from aromatization of male sex steroids in adipose tissue and
      decreased levels of sex hormone-binding globulin. Anesthesia and surgery in obese
      patients can be problematic and special care must be taken to prevent further
      morbidity. Laparoscopic surgery is possible under certain conditions, although
      its role remains to be determined. Prescription of hormone replacement must take
      into consideration several parameters which determine its usefulness and
      surveillance. Obesity is not a contraindication for hormone replacement therapy
      but is frequently a non-indication.

PMID- 9578283
TI  - Digital color imaging colposcopy: a matter of choice.
AB  - OBJECTIVE: To describe the technical performance of a digital color imaging
      colposcopy (DCIC) system. STUDY DESIGN: A videocamera has been selected on the
      basis of physical size and technical performance. Four digitizer boards with
      different analogue input signals and different digitizing properties, have been
      tested with a video test image. The technical performance of a DCIC-system has
      been analyzed. RESULTS: A 3-CCD color videocamera gives the best analogue
      registration. Signal transfer by RGB-videosignal gives superior color and spatial
      resolution when compared to Y/C in composite videotransfer. Digitalization of the
      analogue videoimage with less than 24-bit resolution digitizer boards resulted in
      unwanted side effects that were related to the color measurement accuracy.
      CONCLUSIONS: Digital imaging colposcopy requires a 3-CCD videocamera of which the
      videosignal is transferred as an RGB-signal to a digitizerboard with 24-bit
      resolution that provides 16 million different colors. To store the image a large
      medium that is easily accessible is needed.

PMID- 9578284
TI  - Hydatidiform mole with non-metastatic pulmonary complications and a false low
      level of hCG.
AB  - We present a case of hydatidiform mole with non-metastatic pulmonary
      complications and stress that termination of the pregnancy will cure the patient.
      The frequent use of sonography in early pregnancy makes it possible to diagnose
      pathological pregnancies earlier than was possible before. The fact that molar
      pregnancies are now being terminated at an earlier stage means that some of the
      complications associated with advanced moles are seldom encountered today. The
      case also illustrates the so-called 'high dose hook effect' meaning that an
      extremely high level of hCG may falsely be reported to be very low by the
      laboratory.

PMID- 9578286
TI  - Endometrial carcinoma in a post-menopausal woman with atrophic endometrium and
      intra-cavitary fluid: a case report.
AB  - Measurement of endometrial thickness by vaginal ultrasonography is used to detect
      post-menopausal women at risk for endometrial pathology. The efficacy of this
      procedure is doubtful in cases of intrauterine fluid accumulation, which is a
      common finding in this population. We present a case of endometrial carcinoma in
      an asymptomatic, post-menopausal woman with ultrasonographic imaging of an
      atrophic endometrium and intra-cavitary fluid. It may be suggested that, in a
      case of intrauterine fluid accumulation (IFA), endometrial biopsy should be
      performed regardless of the sonographic endometrial thickness, since the fluid
      may increase the intracavity pressure and can mask endometrial pathology.

PMID- 9578285
TI  - Short-term medical complications of 1500 oocyte retrievals for in vitro
      fertilization and embryo transfer.
AB  - OBJECTIVE: To evaluate the different short-term complications after in vitro
      fertilization and embryo transfer. DESIGN: a retrospective study on 7 years in
      the fertility clinic of an university hospital. MATERIALS AND METHODS: Short-term
      medical complications were analysed after 1500 transvaginal ultrasonographically
      guided oocyte retrievals. RESULTS: Ovarian hyperstimulation syndrome (1.8%),
      pelvic infections (0.4%), intraperitoneal bleeding (0.2%) and adnexal torsions
      (0.13%) were observed. One case of adnexal torsion occurred during pregnancy
      (0.18%). Two unusual case of bowel endometriosis were encountered (0.13%).
      CONCLUSIONS: Short-term medical complications after in vitro fertilization and
      embryo transfer are rare (2.8%). This contrast with the high rate of multifetal
      pregnancies which increases maternal and perinatal morbidity and mortality and
      must be considered as the major complication of in vitro fertilization treatment.

PMID- 9578287
TI  - Non-Hodgkin lymphoma during pregnancy.
AB  - The authors report a case of a pregnancy with a Non-Hodgkin lymphoma. A
      histological association of high-grade B-cell and a MALT type lymphoma was found
      which, to their best knowledge, is described for the first time in pregnancy.

PMID- 9578288
TI  - Colorectal cancer incidence trends: good news and bad news.

PMID- 9578289
TI  - Registration of cancer mortality data in a developing area: Chennai (Madras,
      India) experience.
AB  - OBJECTIVES: This study was carried out to evolve a method to improve the
      registration of cancer mortality data in Chennai (Madras, India). METHODS: Data
      on cancer deaths have been collected from the Vital Statistics Department (VSD)
      by a population-based cancer registry (PBCR) in Chennai only since 1982. The low
      mortality-to-incidence ratio during 1982-84 suggested under-registration of
      mortality data. Since 1985, the PBCR has taken special effort to ascertain the
      vital status of cancer cases by sending reply-paid postcards and/or making house
      visits. The data on all deaths occurring in Chennai, irrespective of stated cause
      of death in the death certificate, have been collected from the VSD since 1992.
      RESULTS: Deaths that occurred in Chennai and obtained by sending reply-paid
      postcards and/or making house visits were registered in VSD as non-cancer causes
      of death; hence, these data were not collected from VSD. The sensitivity and
      positive predictive values of death certificates on cancer diagnosis based on
      1992 and 1993 mortality data were 57 percent and 99.5 percent, respectively.
      CONCLUSION: Since the accuracy of death certificate information on cancer
      diagnosis is relatively low in a developing country such as in India, collecting
      data on all deaths will improve the mortality data registration in PBCRs.

PMID- 9578290
TI  - Increasing incidence of colon and rectal cancer among Hispanics and American
      Indians in New Mexico (United States), 1969-94.
AB  - OBJECTIVES: This study evaluates time trends in colon and rectal cancer incidence
      and mortality among the three major race/ethnic groups (Hispanics, American
      Indians, and non-Hispanic Whites) in New Mexico (United States). METHODS: We used
      data from the New Mexico Tumor Registry (NMTR) and computed average annual age
      standardized incidence and mortality rates. Colon cancer incidence rates were
      further examined by anatomical subsite. Estimated annual percent change (EAPC) in
      incidence and mortality over time were computed using Poisson regression.
      RESULTS: Invasive colorectal cancer incidence rates increased from 1969-89 in all
      three race/ethnic groups, but decreased among non-Hispanic Whites in 1990-94,
      while rates continued to increase among minority populations, especially among
      minority men. Over the 26-year period, EAPC in colon cancer incidence among men
      was 3.6 percent for Hispanics, 4.7 percent for American Indians, and 0.7 percent
      for non-Hispanic Whites. Right-sided colon cancers were more common among
      American Indian women, and among all women aged 65 years and older. Mortality
      rates decreased steadily among non-Hispanic Whites over the study period,
      especially among women. CONCLUSIONS: Studies are needed to identify important
      modifiable risk factors and to develop strategies to increase the use of
      colorectal cancer screening-procedures among the minority populations.

PMID- 9578291
TI  - Trends in colorectal cancer incidence in Sweden 1959-93 by gender, localization,
      time period, and birth cohort.
AB  - OBJECTIVES: This study examined invasive colorectal cancer incidence-rates in
      Sweden from 1959 through 1993 (n = 134,643 cases). METHODS: Age-standardized
      rates were calculated using the Swedish population in 1970 as a reference.
      RESULTS: In right-sided colon cancer (ascending and transverse colon including
      right and left flexures), male age-standardized rates rose from 8.0 to 15.0 (1.8
      percent annually, 95 percent confidence interval [CI] = 1.3-2.4) and female rates
      increased from 9.1 to 14.4 (1.5 percent annually, CI = 1.0-2.0). For left-sided
      colon cancer (descending and sigmoid colon), the rates have been stable recently.
      For rectal cancer, the rates among men rose from 18.8 to 23.0 and among women
      from 10.7 to 14.7. For both men and women, the relative risk (RR) of right-sided
      colon cancer had been increasing in successive generations, until leveling-off in
      those born after 1930. The RR of left-sided colon cancer had been almost constant
      for cohorts born before 1930 but steadily decreasing in later-born cohorts. The
      RR of rectal cancer was slightly increasing in successive cohorts. CONCLUSIONS:
      Changes in lifestyle or carcinogenic exposures during early life probably explain
      Swedish colorectal cancer incidence-trends better than improved diagnostic
      activities.

PMID- 9578292
TI  - Nitrate in drinking water and the incidence of gastric, esophageal, and brain
      cancer in Yorkshire, England.
AB  - OBJECTIVES: This small-area ecologic study in Yorkshire, northern England,
      examines the hypothesis that exposure to higher levels of nitrate in drinking
      water increases the risk of stomach, esophageal, or brain cancer in adults.
      METHODS: Nitrate levels over the period 1990-95 and numbers of incident cancers
      from 1975-94 were available for 148 water supply zones, geographically defined
      areas each supplying water of homogeneous chemical composition to an average
      population of around 20,000. RESULTS: No relationship was found between nitrate
      concentrations and the incidence of stomach or esophageal cancers. The incidence
      of cancer of the brain and central nervous system was found to be higher in areas
      with higher nitrate levels, with a relative risk of 1.18 (95 percent confidence
      interval = 1.08-1.30) in the quartile of the population with the highest average
      levels (mean 29.8 mg/l) compared with the lowest quartile (mean 2.4 mg/l). The
      increase in risk remained statistically significant (P < 0.01) after allowing for
      other covariates and for extra-Poisson variation in a regression model.
      CONCLUSIONS: This study does not support the hypothesis of an increased risk of
      stomach or esophageal cancer associated with higher nitrate levels in drinking
      water. The observed relationship with brain cancer requires confirmation in other
      studies, including those involving data on individuals.

PMID- 9578293
TI  - Family history of cancer and autoimmune disease and risk of leukemia in infancy:
      a report from the Children's Cancer Group (United States and Canada).
AB  - OBJECTIVES: As there are some suggestions that a family history of cancer or
      autoimmune disease might be associated with an increased risk of leukemia in
      children, we explored this possibility using data from a matched case-control
      study conducted by the Children's Cancer Group. METHODS: We compared the family
      history of cancer and autoimmune diseases of 302 infant leukemia cases (diagnosed
      within the first 18 months of life) with that of 668 individually matched
      controls in the United States and Canada. RESULTS: Although not significant,
      cancer history in parents was found to be associated with an elevated risk of
      infant leukemia (odds ratio [OR] = 1.4, 95 percent confidence interval [CI] = 0.6
      3.6), predominantly acute myeloid leukemia (AML) (OR = 2.2, CI = 0.6-9.0). Cancer
      history among second-degree relatives was also related to a nonsignificantly
      elevated risk of AML. Family history of autoimmune diseases, on the other hand,
      was generally not found to be related to the risk of infant leukemia. CONCLUSION:
      This study provided no strong evidence that family history of cancer or
      autoimmune disease is a major risk factor for infant leukemia.

PMID- 9578295
TI  - Cancer risk following appendectomy for acute appendicitis (Denmark).
AB  - OBJECTIVE: Epidemiologic studies have not been able definitely to exclude that
      appendectomy carries a cancer risk. This study was conducted to clarify whether
      appendectomy is associated with a subsequent increase in cancer risk, since
      appendectomy is frequently an elective procedure. METHODS: The present study
      included more than 82,000 persons who underwent appendectomy for acute
      appendicitis during 1977-89 according to the nation-wide Danish Hospital
      Discharge Register. During a follow-up interval of up to 17 years, cancer
      incidence was assessed by linkage to the Danish Cancer Registry and compared with
      the incidence in the general population of Denmark. RESULTS: The total number of
      malignancies among appendectomized persons was 1.05 times higher than expected
      with 95 percent confidence intervals of 0.99-1.11. There was no clear significant
      excess of any specific cancer type. CONCLUSION: During a postsurgery period of
      nearly two decades, results of our study did not support the hypothesis that
      either appendectomy or acute appendicitis are likely to be associated with
      malignant neoplasms.

PMID- 9578294
TI  - A European validation study of smoking and environmental tobacco smoke exposure
      in nonsmoking lung cancer cases and controls.
AB  - OBJECTIVES: The purpose of this study was to validate, in a case-control study,
      the reporting by lung cancer cases and controls of their own lifetime smoking
      habits and of the smoking habit of the spouse. METHODS: In a multicenter (Sweden,
      Spain, Italy) case-control study of environmental tobacco smoke (ETS) and lung
      cancer, subjects were screened by repeated probing to exclude regular smokers of
      one cigarette/day or more for one year or more, and to quantify any occasional
      smoking. We then performed a short validation interview with next-of-kin in three
      centers. RESULTS: Only five of 408 index subjects who had never smoked regularly
      (1.7 percent) were reported by next-of-kin to be former regular smokers. These
      subjects had a cumulative lifetime consumption of cigarettes below 1.1 pack
      years. Among 351 subjects with quantitative smoking information from both sources
      who reported ever smoking 400 cigarettes or less (the definition of never-smoker
      used in the multicenter ETS study), nine subjects (2.6 percent) had smoked more
      than this amount occasionally according to next-of-kin. Misclassification was not
      higher for cases than controls. Relative risks for lung cancer associated with
      indicators of ETS exposure were not substantially altered by excluding the nine
      possibly misclassified subjects. The reports from 223 pairs of index subjects and
      next-of kin regarding the cumulative amount smoked by the spouse agreed quite
      well (Spearman's rank correlation 0.75 for reported smokers, 0.92 for all
      subjects). Only one index subject failed to report a spouse who had smoked
      regularly (99 percent sensitivity). CONCLUSIONS: Smoking status and exposure to
      spousal ETS as reported by lung cancer cases and controls agreed strongly with
      reports by next-of-kin. Overall, our results suggest that bias from smoker
      misclassification is likely to be insignificant, and they contribute to the
      evidence linking exposure to ETS with an increased risk of lung cancer.

PMID- 9578296
TI  - Breast cancer in Australian women under the age of 40.
AB  - OBJECTIVES: A case-control-family study of breast cancer in women under the age
      of 40 was carried out in Melbourne and Sydney, Australia, from 1992 to 1995 to
      determine the risk factors for these women. Subjects included 467 incident cases
      identified by state cancer registries and 408 population-based controls. METHODS:
      All participants completed a structured risk-factor questionnaire and family
      pedigree during an in-person interview. Where possible, cancers in first- and
      second-degree relatives were verified. RESULTS: Multiple logistic regression
      analysis showed that the strongest risk factor for breast cancer was a family
      history of the disease -- having at least one affected first-degree relative
      trebled the risk (relative risk [RR] = 3.3, 95 percent confidence interval [CI] =
      1.9-5.8). Risk increased with height by three percent (standard error [SE] of one
      percent) per cm, and after adjusting for height, there was evidence for a
      decreased risk in women weighing 73 kg or more. There was an increased risk of
      breast cancer after the first full-term birth (RR = 1.8, CI = 1.0-3.5) but this
      risk fell by 30 percent (SE = 11 percent) with each subsequent livebirth.
      CONCLUSIONS: The effects of other reproductive factors and oral contraceptive
      use, although not nominally significant, were in accord with published findings
      from similar studies in young women. This study of Australian women has indicated
      that some risk factors for breast cancer in women under age 40 differ from those
      reported for older women either in direction (e.g., weight) or relative
      importance (e.g., family history).

PMID- 9578298
TI  - Tea and coffee consumption and the risk of digestive tract cancers: data from a
      comparative case-referent study in Japan.
AB  - OBJECTIVES: The purpose of this study was to examine the hypothesis that tea and
      coffee consumption have a protective effect against development of digestive
      tract cancers. METHODS: A comparative case-referent study was conducted using
      Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC)
      data from 1990 to 1995 in Nagoya, Japan. This study comprised 1,706
      histologically diagnosed cases of digestive tract cancers (185 esophagus, 893
      stomach, 362 colon, 266 rectum) and a total of 21,128 non-cancer outpatients aged
      40 years and over. Logistic regression was used to analyze the data, adjusting
      for gender; age; year and season at hospital-visit; habitual smoking and alcohol
      drinking; regular physical exercise; fruit, rice, and beef intake; and beverage
      intake. RESULTS: The odds ratio (OR) of stomach cancer decreased to 0.69 (95
      percent confidence interval [CI] = 0.48-1.00) with high intake of green tea
      (seven cups or more per day). A decreased risk was also observed for rectal
      cancer with three cups or more daily intake of coffee (OR = 0.46, CI = 0.26
      0.81). CONCLUSIONS: The results suggest the potential for protective effect
      against site-specific digestive tract cancer by consumption of green tea and
      coffee, although most associations are limited only to the upper category of
      intake and have no clear explanation for site-specificity.

PMID- 9578297
TI  - Serum hormone levels in relation to reproductive and lifestyle factors in
      postmenopausal women (United States).
AB  - OBJECTIVES: Endogenous sex hormones are thought to be involved in breast and
      endometrial cancers, but few studies have evaluated the relationships between
      hormones and risk factors for these diseases. METHODS: We related serum hormone
      and sex-hormone binding globulin (SHBG) levels to reproductive and lifestyle risk
      factors in a cross-sectional study of 125 postmenopausal women in five geographic
      regions of the United States. RESULTS: The estrogens were associated positively,
      while SHBG was associated negatively with body mass index (wt/ht2). Estrone,
      (E1), estrone sulfate, and bioavailable estradiol (BioE2) were inversely
      associated with height. Androstenedione was positively associated with age at
      menopause, while androstenedione, E1, estradiol, and BioE2 were inversely
      associated with age at menarche. Weekly alcohol drinkers had higher hormone
      levels, and lower SHBG levels than those who abstained. Androstenedione and E1
      decreased with increasing levels of nonrecreational activity. CONCLUSIONS:
      Several of these findings support the hypothesis that breast and endometrial
      cancer risk factors are mediated, in part, through increased endogenous hormone
      levels. The androstenedione findings are of interest in light of studies relating
      androstenedione to endometrial and possibly breast cancer. An association of age
      at menarche with E2, independent of androstenedione, may reflect increased
      aromatase activity in women with earlier menarche.

PMID- 9578299
TI  - Anthropometric predictors of breast cancer incidence and survival in a multi
      ethnic cohort of female residents of Hawaii, United States.
AB  - OBJECTIVES: The purpose of the study was to describe the associations between
      height and body mass index (BMI) (wt/ht2) and breast cancer incidence and
      survival among female residents of Hawaii. METHODS: The study sample is a
      randomly-selected, multi-ethnic cohort of 17,628 women. A total of 378 incident
      breast cancer cases were identified via linkage to the Hawaii Tumor Registry over
      an average follow-up period of 14.9 years. Using age 50 as a cut-point, 86 were
      considered premenopausal cases, and 292 were postmenopausal. Proportional hazards
      analysis was used to describe the risks associated with height and BMI, after
      adjustment for age, education, race/ethnicity, and drinking status. For mortality
      analyses, there were 34 breast cancer deaths among the 365 breast cancer cases
      for which staging information was available. RESULTS: The risk of postmenopausal
      breast cancer was found to increase progressively across approximate tertiles of
      the distribution of height (P = 0.02 for trend test), with a significantly excess
      risk among women in the tallest tertile (risk ratio [RR] = 1.5, 95 percent
      confidence interval [CI] = 1.1-2.1). Baseline levels of BMI were related
      positively to breast cancer incidence among postmenopausal women, after control
      for the above covariates (P = 0.01 for trend test). Among postmenopausal women in
      the highest quintile of the BMI distribution, the RR was 1.5 (CI = 1.0-2.3, P =
      0.04). Further analyses indicated the association between BMI and postmenopausal
      breast cancer incidence was strongest among women aged 65 years and older. After
      statistical control for the above covariates and stage of disease, pre-morbid
      levels of BMI were significantly predictive of death from breast cancer, with an
      approximate nine percent increase in risk per unit increase in BMI (P = 0.01).
      Compared with women in the lowest two quartiles, the RR among the heaviest women
      was 2.2 (CI = 0.9-5.4,P = 0.08). Height was not associated with risk of breast
      cancer mortality. CONCLUSIONS: Relative weight may be an important modifiable
      risk factor for both breast cancer incidence and prognosis. The association
      between height and breast cancer incidence is more difficult to interpret, but
      may underscore the importance of early life exposures in the development of
      breast cancer.

PMID- 9578300
TI  - Incidence of primary cancer of the central nervous system in southeastern
      Netherlands during the period 1980-94. Specialists in neuro-oncology in
      southeastern Netherlands.
AB  - OBJECTIVES: Substantial increases in incidence and mortality rates for primary
      brain tumors have been reported in many, but not all, countries over the past
      several decades. We analyzed incidence rates for (potential) primary malignant
      central nervous system (CNS) tumors in an area (southeastern Netherlands) and
      during a period (1980-94) in which access to healthcare was good and computerized
      tomography (CT) was available. METHODS: Data were obtained from the Eindhoven and
      Maastricht cancer registries, representing a population of 936,000 and 847,000
      inhabitants, respectively. Cases were identified of primary CNS tumors (ICD-0
      codes 191, 192, excluding lymphomas) and brain metastases from an unknown primary
      site (code 199) and data on mortality according to gender and region were
      provided by Statistics Netherlands. RESULTS: Incidence rates in three-year
      periods of primary CNS cancer remained stable, also for patients aged 60 years
      and older. Mortality/incidence ratios ranged from 0.6 to 0.9. Although more CNS
      cancers were histologically verified in recent years, especially in the Eindhoven
      region, changes in diagnosis probably did not influence the overall trend of
      primary CNS cancer. CONCLUSIONS: Major changes in the incidence of the most
      common types of primary CNS cancers (i.e., high-grade astrocytomas) were unlikely
      in southeastern Netherlands.

PMID- 9578301
TI  - The only paper I ever wrote.

PMID- 9578302
TI  - Economic analyses of bone marrow and blood stem cell transplantation for
      leukemias and lymphoma: what do we know?
AB  - The use of blood and/or bone marrow stem cell transplantation (SCT) grew
      extensively in the last decade as technological advances led to improved outcomes
      and wider availability. The first study of SCT costs, however, was not published
      until 1989. This paper summarizes current knowledge about costs and cost
      effectiveness of allogeneic and autologous SCT for leukemias and lymphoma.
      Methodological issues in cost studies such as types of costs, methods of data
      collection, and time horizons are discussed, and studies are evaluated with
      regard to these issues. Considerations specific to economic analyses of SCT are
      considered, including the potential impact of technological changes, learning
      curve effects, and inter-institutional differences.

PMID- 9578304
TI  - Clinical-scale human umbilical cord blood cell expansion in a novel automated
      perfusion culture system.
AB  - Use of umbilical cord blood (CB) for stem cell transplantation has a number of
      advantages, but a major disadvantage is the relatively low cell number available.
      Ex vivo cell expansion has been proposed to overcome this limitation, and this
      study therefore evaluated the use of perfusion culture systems for CB cell
      expansion. CB was cryopreserved using standard methods and the thawed unpurified
      cells were used to initiate small-scale cultures supplemented with PIXY321,flt-3
      ligand, and erythropoietin in serum-containing medium. Twelve days of culture
      resulted in the optimal output from most CB samples. Frequent medium exchange led
      to significant increases in cell (93%), CFU-GM (82%) and LTC-IC (350%) output as
      compared with unfed cultures. As the inoculum density was increased from 7.5 x
      10(4) per cm2 to 6.0 x 10(5) per cm2, the output of cells, CFU-GM, and LTC-IC
      increased. Cell and CFU-GM output reached a plateau at 6.0 x 10(5) per cm2,
      whereas LTC-IC output continued to increase up to 1.2 x 10(6) per cm2. Because
      the increase in culture output did not increase linearly with increasing inoculum
      density, expansion ratios were greatest at 1.5 x 10(5) per cm2 for cells (6.4
      fold) and CFU-GM (192-fold). Despite the lack of adherent stroma, CB cultures
      expressed mRNA for many growth factors (G-CSF, GM-CSF, IL-1, IL-6, LIF, KL, FL,
      Tpo, TGF-beta, TNF-alpha, and MIP-1alpha) that were also found in bone marrow
      (BM) cultures, with the exception of IL-11 (found only in BM) and IL-3 (found in
      neither). Culture output was remarkably consistent from 10 CB samples
      (coefficient of variation 0.3) indicating that the procedure is robust and
      reproducible. Two commercial serum-free media were evaluated and found to support
      only approximately 25% of the culture output as compared with serum-containing
      medium. Implementation of optimal conditions in the clinical scale, automated
      cell production system (CPS) showed that the process scaled-up well, generating
      1.7 x 10(7) CFU-GM (298-fold expansion) from 1.2 x 10(8) thawed viable nucleated
      CB cells (n = 3). The ability to generate >10(7) CFU-GM from <15 ml of CB within
      this closed, automated system without the need for extensive cell manipulations
      will enable clinical studies to test the safety and efficacy of expanded CB cells
      in the transplant setting.

PMID- 9578303
TI  - Outpatient total body irradiation prior to bone marrow transplantation in
      pediatric patients: a feasibility analysis.
AB  - Outpatient total body irradiation (TBI) prior to bone marrow transplantation has
      been accomplished in a total of 68 pediatric patients. The TBI regimen was
      fractionated with a total dose of 12 Gy in eight fractions twice daily.
      Antiemetic therapy consisted of oral ondansetron three times daily throughout the
      TBI course. Eight patients experienced mild nausea without vomiting, and four
      patients experienced mild nausea and vomiting. One patient required intravenous
      hydration after severe nausea and vomiting. Another patient experienced
      intractable diarrhea and dehydration which required inpatient management.
      Outpatient TBI prior to bone marrow transplantation is feasible in pediatric
      patients.

PMID- 9578305
TI  - Purging and haemopoietic progenitor cell selection by CD34+ cell separation.
AB  - Tumour cell contamination of autologous peripheral blood stem cell samples (PBSC)
      and bone marrow (BM) is frequent. Enrichment of CD34+ stem cells is a promising
      approach to purging tumour cells from autografts without damaging progenitor
      cells. Breast cancer cells were seeded (10(-3)-10(-7)) into mononuclear cells
      from G-CSF-mobilised PBSC and BM harvests from patients without breast cancer.
      CD34+ cells were enriched from mixtures either by immunomagnetic separation
      (Isolex-50, and MiniMACS) or by biotin-streptavidin immunoaffinity columns
      (Ceprate-LC). CD34+ cell fractions were determined by FACS, cancer cells were
      detected immunocytochemically with an anti-pancytokeratin antibody. The CD34+
      cells were enriched with a median purity of 92.2% (43.5-96.1) (n = 17) (Isolex
      50), 96.5% (66.6-99.2) (n = 17) (MiniMACS) and 77.9% (31.4-93.6) (n = 15)
      (Ceprate-LC) from PBSC and BM harvests. The percentages of median recovery of
      CD34+ cells were 30.8% (18.6-71.8) (Isolex-50), 69.9% (39.1-100) (MiniMACS) and
      42.9% (23.7-100) (Ceprate-LC). The median tumour cell reductions in log steps
      were 3.7 (2.9-4.3) (n = 13) (Isolex-50), 3.5 (2.6-4.3) (n = 13) (MiniMACS) and
      1.5 (0.9-2.9) (n = 17) (Ceprate-LC). Results were compared statistically by
      univariate analysis. Purity was significantly (P < 0.05) better after MiniMACS
      selection. Recovery rates were significantly different between all devices
      tested. Tumour cell purging was superior after immunomagnetic separation (P <
      0.001). Tumour cell purging is a main objective of CD34+ selection in the
      autologous setting. Our in vitro data clearly indicate that immunomagnetic
      separation is more efficient in the prevention of accidental reinfusion of
      contaminating tumour cells compared to immunoaffinity. However, it is not yet
      known if the same results can be obtained with fresh contaminating tumour cells.

PMID- 9578306
TI  - Leukemia-free survival and mortality in patients with refractory or relapsed
      acute leukemia given marrow transplants from sibling and unrelated donors.
AB  - Between April 1982 and February 1997 39 patients (24 male, 15 female) with
      refractory acute leukemia and a median age of 31 years (19-51 years) received
      allogeneic marrow grafts from an HLA-identical sibling (n = 27), HLA-identical
      unrelated donor (MUD; n = 10) or 1-antigen mismatched unrelated donor (n = 2).
      Twenty-eight patients had acute myelogenous leukemia and 11 acute lymphoblastic
      leukemia. For conditioning most patients received total body irradiation combined
      with cyclophosphamide (n = 23) or etoposide (n = 7). For graft-versus-host
      disease prophylaxis patients received cyclosporin A (CsA) and methotrexate (MTX)
      (n = 20), MTX alone (n = 3), CsA and methylprednisone (n = 6), or CsA alone (n =
      10), respectively. As of June 1997 probability of leukemia-free survival
      projected to 3 years after BMT was 14% for patients given sibling marrow grafts
      and 28% after MUD transplantation. Transplant-related mortality projected to 3
      years was 32% after sibling and 37% after MUD marrow grafting. Although not
      significantly different, probability of relapse projected to 3 years after BMT
      was lower after MUD at 56% compared to 78% with sibling BMT. Thus, high-dose
      chemo/radiotherapy followed by allogeneic marrow infusion has a curative
      potential for patients with refractory leukemia and offers the chance of long
      term disease-free survival for some patients.

PMID- 9578307
TI  - The effect of T cell depletion with Campath-1M on immune reconstitution after
      chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia.
AB  - The prophylactic use of T cell depletion (TCD) strategies for the prevention of
      graft-versus-host disease (GVHD) following allogeneic stem cell transplantation
      remains widespread. Initial reports of high incidence of graft rejection after
      TCD BMT led to a move away from this approach but improved conditioning regimens
      have reduced this risk substantially. The use of TCD has also been associated
      with higher relapse risk post-BMT although the success of donor leukocyte
      infusion (DLI) as treatment for relapse has reduced this problem, especially in
      chronic myeloid leukaemia (CML). Currently the use of TCD BMT is increasing
      particularly due to the relative increase in BMT from non-related donors for whom
      TCD is the optimal GVHD prophylaxis. However, doubts remain over the long-term
      effect on the reconstituted immune system of recipients of TCD BMT, particularly
      in adult recipients. In this study we have undertaken a detailed sequential
      analysis in 23 patients who received allo-grafts from HLA-identical sibling
      donors after high-dose chemo/radiotherapy for acute or chronic leukaemia. Of
      these patients, 11 received non-manipulated grafts, five received 'partially TCD'
      (PTCD) and a further seven received 'fully TCD' (FTCD) bone marrow. T cell
      depletion was performed ex vivo by Campath-1M plus autologous serum as a source
      of complement. Partial TCD describes grafts with a T cell reduction of 1-2 log.
      Full TCD refers to grafts with a reduction of >2.5 log. The decision regarding
      the optimal degree of TCD was clinical and was based upon the perceived relative
      risk of relapse based upon the disease and remission status. All patients were
      monitored for up to 12 months post-BMT with regard to reconstitution of T and NK
      cell subsets. T cell depletion at either level was associated with a slower
      recovery of CD4 cells. This was most marked in the FTCD recipients and lasted
      throughout the period of study. CD8 cell recovery was also slower in the TCD
      recipients but this normalised throughout the 12 months post-BMT. The ratio of
      CD45RA+:CD45RO+ increased in all recipients after month 3. This suggests that a
      degree of extra-thymic T cell maturation can occur in recipients of allogeneic
      BMT. NK cell recovery was more rapid in the TCD recipients and these differences
      were maintained throughout the first year.

PMID- 9578308
TI  - Second allogeneic bone marrow transplants from unrelated donors for graft failure
      following initial unrelated donor bone marrow transplantation.
AB  - Graft failure is a common and severe complication of unrelated donor bone marrow
      transplantation (UD-BMT). However, there are few reports of a second UD-BMT in
      this setting. We describe 12 patients with graft failure (five primary, seven
      secondary) who had a second transplant, five from their original donor and seven
      from a different donor. Their median age was 9 years. Two patients died before
      day 10 of regimen-related toxicity. Nine of 10 evaluable patients engrafted in a
      median of 17 days. Secondary graft failure was seen in one patient. Transplant
      related morbidity was significant. Six of nine developed acute GHVD, there were
      five severe infections and five patients developed Bearman grade 3 or 4
      extramedullary toxicity. Overall, five patients survive at a median of 38 months
      after the second BMT and two are in continuous complete remission. Second
      transplants from unrelated donors for graft failure can result in prolonged
      survival.

PMID- 9578309
TI  - A comparison of the pattern of interstitial pneumonitis following allogeneic bone
      marrow transplantation before and after the introduction of prophylactic
      ganciclovir therapy in 1989.
AB  - A comparison was made of the pattern of interstitial pneumonitis (IP) following
      allogeneic bone marrow transplantation before and after the introduction of
      ganciclovir prophylaxis to minimize the risk of cytomegalovirus (CMV) disease in
      the St Vincent's Hospital bone marrow transplant program in 1989. A total of 456
      recipients of allogeneic transplants were included. 280 received no prophylactic
      ganciclovir while 176 received prophylactic ganciclovir. The overall incidence of
      interstitial pneumonitis dropped from 19.6 to 12.5% (P = 0.03) and this was
      primarily due to a reduction in the incidence of CMV-IP which fell from 12.9 to
      1.7% (P < 0.0005). The incidence of idiopathic IP was not different between the
      two groups (6.3 vs 3.2%), nor was the incidence of Pneumocystis carinii pneumonia
      (2.9 and 0.6%). Prophylactic ganciclovir has thus had a significant impact in
      reducing both the overall incidence of IP and specifically cytomegalovirus IP in
      allogeneic marrow transplant recipients. The most common form of IP in patients
      given prophylactic ganciclovir is now idiopathic interstitial pneumonitis.

PMID- 9578310
TI  - Admission of bone marrow transplant recipients to the intensive care unit:
      outcome, survival and prognostic factors.
AB  - The role of ICU support in BMT patients is controversial. In an era of
      constrained resources, the use of prognostic factors predicting outcome may be
      helpful in identifying patients who are most likely (or unlikely) to benefit from
      this intervention. We attempted to define the survival of patients admitted to
      ICU following autologous or allogeneic BMT and to identify those factors
      important in determining patient outcome. A retrospective study of all adult BMT
      recipients admitted to intensive care over a 6 year study period was performed to
      determine overall and prognostic indicators of poor outcome. Pre-treatment, pre
      ICU admission and ICU admission data were analyzed to identify factors predicting
      long-term survival. 116 patients were admitted to ICU on 135 separate occasions
      with the primary reasons for admission being respiratory failure (66%), sepsis
      associated with hypotension (10%), and cardiorespiratory failure (8%). No pre-ICU
      characteristics were predictive of survival. Univariate analysis identified the
      number of support measures required, the need for ventilation or hemodynamic
      support, the APACHE II score, the year of ICU admission and the serum bilirubin
      as significant predictors of post-discharge survival. On multivariate analysis
      the year of ICU admission, the need for hemodynamic support and the serum
      bilirubin remained significant. The APACHE II score significantly underestimated
      survival in the 46% of patients with scores less than 35, and could only be used
      to predict 100% mortality when it exceeded 45. Twenty-three percent of all BMT
      patients admitted to the ICU and 17% of ventilated patients survived to hospital
      discharge. Of the 27 patients surviving to leave hospital, 16 remain alive with a
      median follow-up of 4.2 years and a mean Karnofsky performance status of 90.
      Although mortality in BMT recipients admitted to ICU is high our results indicate
      that intensive care support can be lifesaving and that the outcome in patients
      requiring ventilation and ICU support may not be as poor as has been previously
      reported. No single variable was identified which could be used to predict
      futility but patients requiring both hemodynamic support and mechanical
      ventilation, and those with an APACHE II score greater than 45 have a very poor
      prognosis and are unlikely to benefit from lengthy ICU support.

PMID- 9578311
TI  - Diagnostic value of hemostatic parameters in bone marrow transplant-associated
      thrombotic microangiopathy.
AB  - We investigated hemostatic parameters in a prospective study of 16 patients who
      received bone marrow transplants (BMT). We found a significant rise in the levels
      of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen
      activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand
      factor antigen, and thrombomodulin on day 14 after transplant compared with
      values before transplant. Protein C and thrombin-antithrombin III levels did not
      change significantly. No significant changes in prothrombin time ratio, activated
      partial thromboplastin time, or protein S were detected. Patients who had grades
      II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher
      level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P
      = 0.0062). Three patients with grades II-IV GVHD developed thrombotic
      microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted
      significantly lower levels of fibrinogen (P = 0.0383), and significantly higher
      levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14
      compared with those patients who did not develop TMA. These results suggest that
      prothrombotic states and endothelial damage may be caused by the conditioning
      regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT
      may be useful in surveillance for TMA because of endothelial cell injury.

PMID- 9578312
TI  - Monitoring of lineage-specific chimaerism allows early prediction of response
      following donor lymphocyte infusions for relapsed chronic myeloid leukaemia.
AB  - Donor lymphocyte infusions (DLI) have been shown to enhance the graft-versus
      leukaemia (GVL) effect and induce haematological and molecular remission in
      patients with relapsed CML following allogeneic bone marrow transplantation
      (BMT). The potent donor cell-mediated cytolysis following DLI may lead to a short
      period of aplasia before the re-establishment of donor haematopoiesis. The
      absence of detectable donor cells in patients prior to DLI infusion may result in
      permanent aplasia in certain patients. We report on four patients who relapsed 1,
      3, 6.5 and 7 years post-BMT for chronic phase CML and were treated with DLI from
      their original BMT donor. Polymorphic short tandem repeats (STRs) were used to
      assess haematological chimaerism both prior to and following DLI. At the time of
      relapse, STR-PCR indicated the presence of donor cells in all four patients, at
      levels ranging from 1-40%. A clinical and molecular response was seen in 4/4
      patients following a short period of cytopenia and all patients remain in
      clinical remission with a follow-up of 2 months-3 years post-DLI. STR-PCR
      indicated that a response was occurring during the period of pancytopenia when
      metaphase analysis was unsuccessful. Lineage-specific analysis of the cellular
      response to DLI was monitored using STR-PCR of peripheral blood (PB) and bone
      marrow (BM) lymphocyte-enriched fractions and CD2-positive and -negative T cell
      fractions. In one patient BM and PB CD34-positive and -negative fractions were
      also assessed. A change in the ratio of donor:recipient cells in the PB
      lymphocyte fraction was the earliest molecular indication of an anti-leukaemic
      response. Subsequent conversion to donor chimaerism occurred in the other
      lineages and the granulocyte fraction was the last lineage to convert. In
      conclusion, lineage-specific STR-PCR permits detailed monitoring of subtle
      changes in donor/recipient cell dynamics in specific lineages following DLI
      during the crucial pancytopenic phase and may be a useful predictor of
      haematological response to DLI therapy.

PMID- 9578313
TI  - Phimosis as a manifestation of chronic graft-versus-host disease after allogeneic
      bone marrow transplantation.
AB  - Chronic GVHD is one of the major complications of BMT, involving a variety of
      organs, but rarely involving the genitourinary system. We report a patient who
      simultaneously developed extensive chronic GVHD and phimosis after BMT. From the
      clinical course and pathological findings, chronic GVHD was considered to be
      responsible for the phimosis. Despite intensive immunosuppressive therapy, the
      phimosis persisted. Phimosis is a rare complication after BMT, which may often
      remain neglected. Possibility of this complication should be considered in
      patients with chronic GVHD.

PMID- 9578314
TI  - Donor leukocyte infusion after allogeneic bone marrow transplantation was not
      effective for relapsed rhabdomyosarcoma.
AB  - A 10-year-old boy with metastatic rhabdomyosarcoma had an HLA-identical sibling
      and received an allogeneic BMT. Recurrence was detected in the BM as the only
      site of treatment failure 12 months after BMT. Donor leukocyte infusion (DLI) was
      chosen as salvage therapy. Although sufficient cells (a total of 29.7 x 10(7)/kg)
      were infused, no signs of acute GVHD nor BM aplasia occurred and the patient died
      of disease progression 9 months after DLI.

PMID- 9578315
TI  - Life-threatening carboplatin hypersensitivity during conditioning for autologous
      PBSC transplantation: successful rechallenge after desensitization.
AB  - Carboplatin hypersensitivity has rarely been reported in patients receiving
      repeated cycles of therapy, but has not been reported in transplant settings. We
      report a case of carboplatin hypersensitivity during conditioning for autologous
      PBSC transplantation. The patient suddenly developed chest tightness, hemoptysis,
      hypoxia and hypotension, resulting in a transient myocardial ischemia. The
      pathophysiologic mechanism for the event seemed to be non-immune-mediated direct
      histamine release given the lack of prior exposure to platinum. Contrary to
      advice not to continue further treatment with carboplatin by some authors, we
      successfully desensitized the patient and subsequently gave more carboplatin as a
      part of conditioning. Awareness of carboplatin as one of the causes of
      hypersensitivity may help avoid further problems either by substitution or
      desensitization, along with premedications.

PMID- 9578316
TI  - Color-flow imaging sonography of portal and hepatic vein flow to monitor
      fibrinolytic therapy with r-TPA for veno-occlusive disease following
      myeloablative treatment.
AB  - Veno-occlusive disease (VOD) is a serious complication of myeloablative therapy
      and stem cell transplantation. We here describe a case of VOD in a patient with
      acute myeloid leukemia (AML), who received an autologous peripheral blood stem
      cell graft after busulphan/cyclophosphamide conditioning in first complete
      remission and who developed severe VOD at day 17. Color-flow sonography of the
      portal and hepatic veins revealed hepatofugal blood flow in the portal vein and
      an absence of flow in the hepatic vein. Treatment with recombinant tissue
      plasminogen activator (t-PA) was started at a dose of 10 mg/day and increased to
      20 mg/day because color-flow sonography indicated no change of blood flow. Daily
      sonography was continued to monitor the portal and hepatic blood flow in order to
      assess the need for continuation of t-PA. Once an objective sonographic
      improvement was observed, t-PA treatment was tapered and stopped. This case
      demonstrates that color-flow sonography can be used to confirm the clinical
      diagnosis of VOD. Furthermore this technique provides a way for easily and
      reliably evaluating the effect in relation to dose of thrombolytic therapy
      needed. It improves the quality of clinical monitoring which is needed for
      effective treatment of VOD while minimizing the risk of serious bleeding
      complications.

PMID- 9578317
TI  - Engraftment of unrelated donor stem cells in children with familial
      amegakaryocytic thrombocytopenia.
AB  - Congenital amegakaryocytic thrombocytopenia is an extremely rare disorder for
      which bone marrow transplantation offers the only possibility for cure. The
      pathophysiology is unclear. Two children with familial amegakaryocytic
      thrombocytopenia underwent unrelated donor transplantation (bone marrow in one,
      umbilical cord blood in the second) after a preparative regimen of
      cyclophosphamide and total body irradiation. Both patients failed initial
      engraftment, required further donor stem cell infusions and are currently well
      with sustained engraftment, 16 months and 7 months after transplantation,
      respectively. The difficulty in achieving engraftment of unrelated donor stem
      cells in these children suggests that in future cases additional measures to
      achieve engraftment may be necessary, for example, a more aggressive preparative
      regimen or an increased stem cell dose.

PMID- 9578318
TI  - IGIV: a potential role for hepatitis B prophylaxis in the bone marrow
      peritransplant period.
AB  - Prevention of hepatitis B virus infection in transplant recipients can be
      difficult. Patients may be unresponsive to vaccination and intolerant of the
      intramuscular injections required to administer hepatitis B immune globulin
      (HBIG). A recipient of HBsAg-positive donor cells for a bone marrow transplant
      received multiple i.m. injections of HBIG. This mode of antibody delivery was
      limited by his thrombocytopenia and neutropenia and alternative forms of passive
      immunization were sought. Four lots of IGIV were investigated for anti-hepatitis
      B surface antibody (anti-HBs) content and all were found to contain significant
      antibody titer. Moreover, IGIV that was administered to four bone marrow
      transplant recipients for medical purposes unrelated to HBV transmission produced
      protective anti-HBs titers in all. These studies suggest IGIV may be useful for
      HBV prophylaxis in the appropriate setting or if HBIG is unavailable. The optimum
      regimen for HBV prevention in distinct transplant settings needs to be
      determined.

PMID- 9578319
TI  - Protein kinase inhibitors: the tyrosine-specific protein kinases.
AB  - Inhibitors for tyrosine-specific protein kinases ultimately may constitute a
      novel family of medicinally active agents. Unfortunately, the challenges
      associated with the acquisition of inhibitors for these enzyme targets are unlike
      any that have ever been encountered in medicinal chemistry. Protein kinases pose
      a variety of obstacles in regard to inhibitor design, nearly all of which deal
      with, in one fashion or another, the issue of specificity. The protein kinase
      family is extraordinarily large, with estimates that the human genome codes for
      as many as 2000 protein kinases. Furthermore, inhibitors that are directed to the
      ATP-binding sites of these enzymes must contend with the presence of a large
      number of other ATP-utilizing proteins and, in addition, must compete with the
      high intracellular concentrations of ATP. Although specificity ultimately may
      prove to be less of a concern with peptide-based inhibitors, these agents neither
      are readily bioavailable nor do they bind with the requisite affinity to the
      protein-binding domains of protein kinases. In the face of these challenges, an
      enormous number of inhibitors have been synthesized and evaluated for the
      tyrosine-specific protein kinases. The advantages and disadvantages associated
      with inhibitors that are targeted to the ATP-binding site, the protein-binding
      site, and nonactive site regions required for appropriate subcellular
      localization are discussed. The handful of tyrosine-specific protein kinases that
      have been selected as targets to date and their roles in various disease
      processes are described as well.

PMID- 9578320
TI  - Biological effects of inhibitors of S-adenosylhomocysteine hydrolase.
AB  - S-Adenosylhomocysteine (AdoHcy), formed after the donation of the methyl group of
      S-adenosylmethionine to a methyl acceptor, is hydrolyzed to adenosine and
      homocysteine by AdoHcy hydrolase physiologically. The administration of the
      inhibitors of AdoHcy hydrolase to cells or animals normally results in an
      accumulation of cellular AdoHcy higher than those found in controls, which is
      often accompanied by a simultaneous rise in S-adenosylmethionine because of the
      feedback inhibition by AdoHcy on most methylation reactions. AdoHcy hydrolase has
      become a tantalizing pharmacological target for inhibition since its blockade can
      affect cellular methylation of phospholipids, proteins, small molecules, DNA, and
      RNA. Indeed, all of these different methylation reactions have been found to be
      inhibitable by the nucleoside inhibitors/substrates of AdoHcy hydrolase. Among
      the interesting effects are the activation of genes, induction of cellular
      differentiation, increased expression of transcription factors, and sometimes the
      repression of genes. Furthermore, some of the nucleosides show remarkable
      antiviral activities in vitro and in vivo. However, the mode of action of the
      inhibitors appears complex. Although the inhibition of methylation might account
      for some of the biological effects, the ability of some of the nucleoside
      inhibitors to undergo metabolic phosphorylation to nucleotides may account for
      part of their biological activities. The defining mode of action responsible for
      their biological effects still awaits biochemical elaboration, especially
      regarding their antiviral effects, induction of genes, or cellular
      differentiation.

PMID- 9578321
TI  - Molecular markers of carcinogenesis.
AB  - The protein products of oncogenes and tumor suppressor genes play critical roles
      in the development of many cancers. The expression of a number of these proteins
      can be detected in extracellular fluids such as blood. This article reviews the
      literature on the application of methods for the detection of the proteins of
      oncogenes and tumor suppressor genes in the blood of humans with cancer or at
      risk for the development of cancer. The detection of these proteins in blood may
      be useful molecular markers of carcinogenesis that could play an important part
      in cancer diagnosis, prognosis, and prevention.

PMID- 9578322
TI  - Hyperthermia in brain hemorrhage.
AB  - Hemorrhage in the midbrain and/or pons in patients is often associated with
      increased metabolism, resulting in hyperthermia. We have recently reported that
      hyperthermia develops in anesthetized rats following prepontine knife-cuts or
      procaine microinjections into the midbrain or upper pontine region. It was
      concluded that the hyperthermia in the animals was caused by the removal of a
      tonic inhibitor mechanism of heat production that exists in the lower midbrain.
      The present paper proposes a new hypothesis that the hyperthermia in patients
      with brainstem hemorrhage is caused by disinhibition of heat production due to
      the release of such a lower-midbrain mechanism.

PMID- 9578323
TI  - Neuroglia: possible role in thermogenesis and body temperature control.
AB  - The neuroglia, especially astrocytes, constitute a cell mass capable of adaptive
      heat production, since both the metabolic substrates and the biochemical
      machinery for energy production and its regulation seem to be available in these
      cells. Earlier physiological studies from this laboratory have provided
      circumstantial evidence that rodents such as rats and rabbits may indeed be
      capable of increasing their cerebral heat production during acute cold exposure.
      Recent relevant literature on the ability of neuroglia of the mammalian CNS to
      synthesize and release different transmitters and modulators and to communicate
      mutually with neuronal elements is discussed in support of the idea that
      different glial cell types could also contribute to the central regulation of
      body temperature in addition to the more established similar function of the
      neuronal pathways. The present hypothesis may have relevance to changes in glial
      cell mass and activity that occur in patients during the course of aging, or in
      gliosis with a consequent tendency for epilepsy caused by head trauma, with a
      consequent decrease or increase of intracranial metabolic rate, respectively.
      Also, the possibility for glial contribution to the thermoregulatory changes seen
      in psychoses is discussed.

PMID- 9578324
TI  - Can our thermoregulatory system anticipate temperature exposure?
AB  - After daily heat exposure for approximately 5 h/day during a fixed time for more
      than 5 consecutive days, body core temperature of rats decreases during the
      period when they were previously exposed to heat. The fall in body temperature
      persists for a few days after terminating the timed daily heat exposure.
      Additionally, various thermoregulatory changes to resist heat are brought about,
      especially during the specific heat-exposure period. It is therefore hypothesized
      that the thermoregulatory system can memorize a time for heat exposure and that,
      in accordance with the memory, thermoregulatory responses for neutralizing heat
      stress are induced, even without actual heat exposure, around the period
      corresponding to that of the previous heat exposure.

PMID- 9578325
TI  - Selective brain cooling in hyperthermia: the mechanisms and medical implications.
AB  - We hypothesize that selective brain cooling (SBC) can occur in hyperthermic
      humans despite the fact that humans have no carotid rete, a vascular structure
      that facilitates countercurrent heat exchange and that is located at the base of
      the skull in some mammals. We postulate that an increase in emissary and angular
      ocular venous flows contributes to SBC. The efficiency of SBC is increased by
      evaporation of sweat on the head and by ventilation through the nose. A body
      position that increases the intravenous pressure gradient across the skull
      increases emissary flows and hence enhances the efficiency of SBC. The validity
      of using tympanic temperature as an index of brain temperature is also
      postulated.

PMID- 9578326
TI  - Pyretic and antipyretic signals within and without fever: a possible interplay.
AB  - Current concepts on the pathogenesis of fever emphasize the importance of the
      cytokine-prostaglandin cascade. This humoral line mediates nonthermal signals to
      the brain, while the thermal signals supply feedback from the thermoreceptors.
      However, the humoral line cannot alone account for the whole febrile response.
      Here, we hypothesize that, besides this humoral mediatory mechanism, nonthermal
      neural signals of abdominal origin conveyed mainly by the vagus nerve are also
      important pro-pyretic factors. The pro-pyretic mechanisms are proposed to be in a
      dynamic balance with endogenous antipyretic mechanisms that also form an integral
      part of the normal reaction to pyrogens. Further, it is hypothesized that the
      role of such neural and humoral signals either for elevation or depression of
      body temperature is not limited to fever but has an important role also in
      nonfebrile thermoregulation.

PMID- 9578327
TI  - Fever and hypothermia: two adaptive thermoregulatory responses to systemic
      inflammation.
AB  - Entering both the old dispute (whether fever is adaptive or maladaptive) and its
      more recent modification (whether hypothermia is protective or detrimental in
      systemic inflammation), we suggest a new solution. We hypothesize that fever and
      hypothermia represent two different strategies of fighting systemic inflammation,
      each developed as an adaptive response to certain conditions, and each beneficial
      under these conditions. The antimicrobial and immunostimulating benefits of a
      high body temperature could be easily offset by its high energy cost. Fever,
      therefore, is protective only when there is no immediate threat of a substantial
      energy deficit. Hypothermia, on the other hand, constitutes a response aimed at
      energy conservation and, as such, is beneficial exactly under the conditions of a
      substantial energy deficit. The two thermoregulatory responses represent two
      complementary strategies of survival in systemic inflammation: fever ensures the
      active attack against the pathogen; hypothermia secures the defense of the host's
      vital systems. The importance of each response's contribution to the whole
      campaign depends on the severity of the pathogenic insult, premorbid pathology,
      and current conditions (stress, nutrition, ambient temperature, etc.).

PMID- 9578328
TI  - Aspirin-like drugs cause gastrointestinal injuries by metallic cation chelation.
AB  - Aspirin-like (nonsteroidal anti-inflammatory) drugs may cause injuries including
      ulcers to the gastrointestinal tract by chelation of the divalent and/or
      multivalent metallic cations in the gastrointestinal mucus and mucosa, as
      suggested by the chemical properties of these drugs and supported by experimental
      and clinical data.

PMID- 9578329
TI  - A chelate theory for the mechanism of action of aspirin-like drugs.
AB  - Two hundred years after the discovery of the pharmaceutical usefulness of
      aspirin, it and aspirin-like drugs, a family with an ever-increasing number of
      members, are an indispensable part of modern life. However, the question as to
      how these drugs work in the body has remained unsettled. It is postulated here
      that this group of drugs may exert their therapeutic (and adverse) effects by
      chelating various physiologically important metallic cations in the body. The
      chelate theory is supported by the vast majority, if not all, of the observations
      on these drugs made in the past.

PMID- 9578330
TI  - The synergistic effect of simultaneous addition of retinoic acid and vitamin D3
      on the in-vitro differentiation of human promyelocytic leukemia cell lines could
      be efficiently transposed in vivo.
AB  - Both human cell lines HL-60 and AML-193 exhibit a myeloblastic and promyelocytic
      morphology, respectively, but may be regarded as bipotent leukemic precursors.
      They can be triggered to differentiate to either granulocytes or monocytes upon
      retinoic acid (RA) or 1,25-dihydroxyvitamin D (D3) addition, respectively. We
      have investigated the effect of combined addition of these chemical inducers on
      the in-vitro differentiation of both cell lines. RA and D3 added together exert
      synergistic effects on the in-vitro maturation of these myeloid cell lines.
      Interestingly, the additive effects were lost if the cells were incubated with
      the inducers added at sequential times. The synergistic effect could be
      transposed in vivo and could be clinically significant in the treatment of the
      promyelocytic leukemia. This clinical strategy may help to prevent retinoic acid
      resistance or to overcome it in patients relapsed after RA therapy and usually
      unresponsive to a reinduction therapy with RA alone.

PMID- 9578331
TI  - An autoimmune response causes transmissible spongiform encephalopathies.
AB  - Misfolded prion protein (PrP) is generally accepted as causing transmissible
      spongiform encephalopathies (TSEs) by aligning alongside normal host prion
      protein and inducing it to change to the misfolded configuration. This paper
      disputes this theory, and proposes that, rather than causing TSEs, misfolded PrP
      is the result of an autoimmune response to the host PrP, a component both of
      nerve cells and of lymphocytes. Autoimmunity is initiated by detachment of the
      phosphotidylinositol glycolipid anchor as a result of exposure to organophosphate
      pesticides. Once PrP is detached, antibodies are mobilized against it. In some
      individuals, point mutations, like the codon 129 met-val substitution, have
      evolved as a self-defence mechanism, causing a change in PrP to the misfolded,
      protease-resistant form seen in TSEs. Increased PrP production, both in response
      to nerve damage, and as a component of lymphocytes stimulated to proliferate in
      response to PrP, produces a positive feedback mechanism, resulting in symptoms of
      brain destruction.

PMID- 9578332
TI  - Short note: Behavioral genetic research: achievements and concerns.
AB  - Behavioral genetic research is advancing rapidly. This can result in the
      improvement in diagnosis and treatment of psychiatric disorders. However,
      humankind may not be able to use reasonably the results of research into the
      genetic basis of behavior, and genetic discoveries may lead to the violation of
      human rights. The author calls for international cooperation in order to make
      sure that the results of genetic research will be used for the sake of people.

PMID- 9578333
TI  - On the extrapyramidal side-effects of antipsychotics with combined dopamine and 5
      HT-blocking effects.

PMID- 9578334
TI  - A review of associations between Crohn's disease and consumption of sugars.
AB  - OBJECTIVES: To critically review the available literature reporting associations
      between the onset of Crohn's disease and intakes of sugars or sugar-containing
      foods. To evaluate published evidence on the use of dietary manipulation of
      sugars in the treatment of Crohn's disease. DESIGN: All publications from
      refereed journals which reported intakes of sugars and sugar-containing foods in
      the context of Crohn's disease onset or treatment were selected. CONCLUSION:
      Evidence suggesting a relationship between sugars and onset of Crohn's disease
      was inconsistent and subject to important methodological limitations. There was a
      clear lack of distinction between reporting of current, as opposed to,
      retrospective intakes. There appeared to be no clinical advantage to the use of
      reduced sugar diets in Crohn's disease treatment.

PMID- 9578335
TI  - Effect of psyllium on gastric emptying, hunger feeling and food intake in normal
      volunteers: a double blind study.
AB  - OBJECTIVE: To assess whether psyllium, a soluble dietary fibre, could, at an
      acceptable dose (7.4 g), delay gastric emptying of a low-calorie meal, and reduce
      hunger feeling and energy intake, without requiring intimate mixing with the
      meal. DESIGN: A double blind randomized cross over study with 14 normal
      volunteers, to evaluate the effect of this dose of psyllium on postprandial serum
      glucose, triglycerides and insulin levels, and on gastric fullness, hunger
      feeling and food intake. METHODS: Gastric emptying was measured using a standard
      double-radiolabeled 450 kcal meal and feelings by visual analogic scales. The
      postprandial serum glucose, triglycerides and insulin levels were also
      determined. RESULTS: No delay in the gastric emptying of the solid and liquid
      phases of the meal was observed with psyllium. After the meal, hunger feelings
      and energy intake were significantly lower during the psyllium session than
      during the placebo session (13% and 17% lower respectively; P < 0.05).
      Postprandial increase in serum glucose, triglycerides and insulin levels was less
      with psyllium than with placebo (P < 0.05). CONCLUSIONS: Psyllium reduces hunger
      feelings and energy intake in normal volunteers at reasonable dose and without
      requiring mixing with the meal. It does not act by slowing down the gastric
      emptying of hydrosoluble nutrients, but by increase in the time allowed for
      intestinal absorption, as suggested by the flattening of the postprandial serum
      glucose, insulin and triglycerides curves.

PMID- 9578336
TI  - Diet during pregnancy in a population of pregnant women in South West England.
      ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.
AB  - OBJECTIVE: To describe the diet of a population of pregnant women. SUBJECTS:
      Eleven thousand, nine hundred and twenty-three pregnant women resident in the
      south-west of England. DESIGN: A self-completion unquantified food-frequency
      questionnaire was sent to the women at 32 weeks gestation. Estimated daily
      nutrient intakes were calculated from the answers to the questionnaire. RESULTS:
      On the whole, nutrient intakes of the pregnant women in this survey compared very
      closely with the reported nutrient intakes for all women aged 16-64 in the last
      Dietary and Nutritional Survey of British Adults (DNSBA). The exceptions were
      sugar, calcium, folate and vitamin C where the estimated intakes were somewhat
      higher, and retinol, where the estimated intake was somewhat lower than the
      DNSBA. Mean and median estimated nutrient intakes were above the RNIs for the
      majority of nutrients investigated except for energy, iron, magnesium, potassium
      and folate. Levels of supplementary vitamin and mineral use were fairly low, the
      two most commonly taken supplements were iron--taken by 22.5% of the pregnant
      women before 18 weeks and 43% at 32 weeks, and folate, taken by 9% and 18% of the
      women, respectively. CONCLUSIONS: These results suggest that the diets of
      pregnant women in this country are likely to contain adequate amounts of most
      nutrients, the most likely exceptions being iron, magnesium, potassium and
      folate. The relatively low intakes of folate and small proportion of women taking
      folate supplements is of concern, because of the association between inadequate
      amounts of folate in the diet and neural tube defects.

PMID- 9578337
TI  - Financial difficulties, smoking habits, composition of the diet and birthweight
      in a population of pregnant women in the South West of England. ALSPAC Study
      Team. Avon Longitudinal Study of Pregnancy and Childhood.
AB  - OBJECTIVE: To investigate the relationships between self-assessed financial
      difficulties, diet in pregnancy and birthweight. DESIGN: Information on diet
      composition, difficulty in affording food, smoking habits and parity was
      collected by self-completion questionnaires at 32 weeks of pregnancy. Information
      on birthweights was obtained from hospital records. SUBJECTS: A geographically
      defined population 11833 pregnant women resident in the South-West of England.
      MAIN OUTCOME MEASURES: Nutrient intakes, food choices and birthweight. RESULTS:
      Women with greater difficulty in affording food had lower intakes of protein,
      fibre, vitamin C, niacin, pyridoxine, iron, zinc, magnesium and potassium than
      did women with little or no difficulty. They were more likely to use cooking and
      spreading fats with a high saturates content, and less likely to eat fish, fruit,
      vegetables and salad. In a multivariate analysis including parity and smoking
      status, financial difficulty was found to have no significant relationship with
      birthweight. CONCLUSION: The quality of diet in pregnancy falls with increasing
      difficulty in affording food. However, this does not appear to affect mean
      birthweight of infants born after 32 weeks gestation.

PMID- 9578338
TI  - Dietary composition and ovarian function among Lese horticulturalist women of the
      Ituri Forest, Democratic Republic of Congo.
AB  - OBJECTIVE: To assess dietary composition in relation to energetic status and
      ovarian function. DESIGN: An eight-month prospective study undertaken in 1989.
      SETTING: Ituri Forest, northeast Democratic Republic of Congo. SUBJECTS: Sixty
      four female volunteers of reproductive age (16-45), with a subsample of 30 for
      nutritional focal follows, 39 for analysis of salivary progesterone levels, and
      18 for analysis of salivary oestradiol. INTERVENTIONS: Regular anthropometric
      measurements of heights, weights, and mid-triceps skinfolds, 204 h of nutritional
      focal follows when all foods prepared and consumed were recorded and weighed,
      analysis of dietary composition using African food tables, collection of saliva
      samples every-other day for radioimmunoassay of salivary oestradiol and
      progesterone. RESULTS: The primary staple in the Lese diet is manioc, consumed at
      nearly every meal, but the diet is subject to seasonal fluctuations. Important
      seasonal crops are groundnuts and rice. Carbohydrates comprise 64% of the diet,
      protein 14% and fat 22%, but seasonal fluctuations in food items create
      significant differences in protein content (P = 0.007). Energy intake falls by
      25% in the hunger season. Lese energy balance reflects this lack with women
      losing a mean 7% of total body weight. The mean BMI for Lese women at the
      beginning of the study was 22.8 but, during the hunger season, the BMI for 20% of
      women fell to < 18.5, indicative of chronic energy shortage. Mean levels of Lese
      salivary oestradiol and progesterone are chronically and significantly lower than
      healthy, Western controls (P = 0.0001 for progesterone; P = 0.03 for follicular
      values of oestradiol, P = 0.0001 for mid-cycle values, and P = 0.0002 for luteal
      values). Mean salivary progesterone levels were significantly lower for those
      Lese women losing weight (P = 0.03), and significantly lower for weight-loss
      women when comparing levels at the beginning and end of the hunger season (P =
      0.03). DISCUSSION: The relatively low-fat, high-fibre diet of the Lese appears
      healthy, but there are occasional seasonal deficiencies in protein-energy and
      micronutrient content, especially for pregnant and lactating women. Dietary
      composition may affect Lese levels of reproductive steroids, partly explaining
      the chronically low salivary oestradiol profile of this population.

PMID- 9578339
TI  - Malignant epithelial tumours in the upper digestive tract: a dietary and socio
      medical case-control and survival study.
AB  - OBJECTIVE: The aim of the present study was to elucidate the influence of social,
      dietary and environmental factors on the incidence of malignant epithelial
      tumours in the upper digestive tract and on the prognosis of patients with these
      cancers. DESIGN: A population-based case-control study was carried out, and the
      patients in the study were included in a survival analysis. SETTING: The study
      was carried out at the Department of Otorhinolaryngology at Ulleval University
      Hospital, Oslo, Norway. SUBJECTS: In the case-control study, 84 patients and 89
      controls were included. Only the patients were included in the survival analysis.
      RESULTS: Smoking showed the highest odds ratio (OR) for morbidity (OR = 29). The
      patients had in general a lower social status, and a higher alcohol intake (OR =
      6.6). For both beta-carotene and vitamin C, the ORs decreased with increasing
      intake (OR = 0.2 and 0.3, respectively). Increased ORs were associated with low
      values for haemoglobin, iron, TIBC, folic acid, magnesium and especially for
      albumin (OR = 14), and with high values for ferritin, vitamin B12 and thiocyanate
      (a marker for smoking). Stage of the disease was an important prognostic factor.
      The relative risk (RR) of dying for disseminated vs localised tumours being 3.2.
      A poorer prognosis was linked to higher age, to smoking vs no smoking (RR = 2.3),
      and to lower levels of haemoglobin, albumin, magnesium and thiocyanate.
      CONCLUSIONS: Strong beer, liquor, consumption of milk and table fat, low social
      status and smoking seemed to have a negative impact on both disease and survival.
      Fruit and vegetables might, however, reduce the risk. Whereas low serum albumin,
      iron and magnesium indicated a high OR for cancer, vitamin C and beta-carotene
      had the opposite implication. No significant implications on survival could be
      detected in blood chemistry beyond the stage of disease.

PMID- 9578340
TI  - Concordance of diet with the recommended cholesterol lowering diet in patients
      with coronary heart disease.
AB  - OBJECTIVE: The aim was to examine the concordance of diet with the recommended
      cholesterol lowering diet in Coronary Heart Disease (CHD) patients receiving
      usual care. DESIGN: CHD patients were selected for a survey from hospital records
      at least six months after hospitalization. Four patient groups divided according
      to the severity of disease were examined in cross-sectional setting. Food records
      and fatty acid composition of serum lipids were used to assess dietary intake.
      SUBJECTS: The study population consisted of 109 patients with coronary bypass
      grafting, 106 patients with balloon angioplasty, 101 patients with acute
      myocardial infarction and 99 patients with acute myocardial ischemia. RESULTS:
      Concordance of the diet with the cholesterol lowering diet was similar in the
      patient groups. One third of the patients achieved the recommended fat intake and
      only one fourth achieved the recommended saturated fat intake. Concordance was
      better in the patients who also used lipid lowering drugs, but previous
      myocardial infarction did not affect dietary intake of fat and saturated fat.
      Diabetic or obese patients tended to have a higher intake of saturated fat.
      Myristic acid in cholesterol esters, triglycerides and phospholipids and also
      palmitic and linoleic acids in triglycerides were markers of dietary saturated
      fat intake. CONCLUSIONS: Concordance of the diet with the recommended cholesterol
      lowering diet in CHD patients was moderate. Concordance was not affected by
      disease severity or previous myocardial infarction and was slightly worse in CHD
      patients who had diabetes or were obese or did not use lipid lowering drugs.

PMID- 9578341
TI  - The small child: anthropometric and physical performance characteristics of short
      for-age children growing in good and in poor socio-economic conditions.
AB  - OBJECTIVE: To ascertain whether individuals whose short stature is caused by poor
      living conditions differ in their other biological characteristics from those
      individuals who grow short, supposedly due to their genetic endowment, under
      favourable environmental conditions. DESIGN: From the growth survey of nearly
      4000 children of the 'Cape Coloured' community aged 6-18 y half of whom lived in
      the middle-class suburbs of Cape Town [high socio-economic status (SES)], the
      other half who lived in poor rural settlements (low SES), boys and girls of
      similarly short stature were selected. Average body height by sex and age in each
      selected sample was close to the 5th percentile of height distribution among all
      high SES individuals surveyed. SETTING: Cape Town and neighbouring rural
      settlements in South Africa. SUBJECTS: Four thousand children of the Cape
      Coloured community aged 6-18 y. Among these were 109 high SES boys, 123 high SES
      girls, 302 low SES boys and 344 low SES girls selected for short stature study.
      INTERVENTIONS: Anthropometric measurements in public schools with appropriate
      permissions. RESULTS: Both short stature males and females from the low SES group
      tended to be significantly (P < 0.05) different from the high SES group of
      comparable stature in having lower body weights, shorter limbs, longer trunks,
      narrower shoulders, hips and chests, thinner skinfolds, smaller arm
      circumferences, and were very notably weaker and had poorer neuromuscular
      reaction times. Biepicondylar widths and pulse rates were little different
      between groups. Genetically short children do differ in various anthropometric
      and functional traits from those who are small from environmental causes.

PMID- 9578342
TI  - Antioxidant fortified margarine increases the antioxidant status.
AB  - OBJECTIVE: To assess the effect of supplementation with an antioxidant fortified
      margarine on the body's antioxidant status and on parameters of oxidative damage
      to lipids. DESIGN: Single blind, placebo controlled trial, two treatment groups
      balanced for sex, age and Quetelet Index. SETTING: Unilever Research
      Laboratorium, The Netherlands. SUBJECTS: Thirty-one healthy adult volunteers
      accomplished the study. Volunteers were recruited among inhabitants of the
      surrounding area of the research laboratory. INTERVENTIONS: Volunteers consumed
      during the four weeks either 15 g/d of an antioxidant fortified margarine
      (providing 121 mg vitamin C, 31 mg vitamin E, 2.7 mg alpha-carotene and 5.3 mg
      beta-carotene) or an ordinary margarine. Fasting blood samples were taken before
      and at the end of the study. RESULTS: Consumption of the antioxidant fortified
      margarine significantly increased the levels of the supplied antioxidants in
      plasma and LDL as compared to the changes found after consumption of the control
      margarine, with the largest increases found in LDL levels of alpha-carotene (15.5
      fold increase, 95% CI: 8.4-27.8-fold) and beta-carotene (4.3-fold increase, 95%
      CI: 2.2-7.9-fold). This increased antioxidant status in the antioxidant fortified
      margarine group resulted in a significantly increased total antioxidant activity
      of LDL and resistance of LDL to oxidation (lag time and rate of oxidation) as
      compared to baseline but not in comparison to the changes found in the control
      group. CONCLUSION: Consumption of moderate doses of vitamin E, vitamin C, alpha
      carotene and beta-carotene, supplied in a full-fat margarine and consumed as part
      of a normal diet, effectively increases the blood levels of these antioxidants.

PMID- 9578343
TI  - Exercise in dietary restrained women: no effect on energy intake but change in
      hedonic ratings.
AB  - OBJECTIVES: To investigate the short-term effects (one day) of exercise and diet
      composition on appetite control in restrained females. DESIGN: 2x2 repeated
      measures design, with exercise and lunch type used as the repeated factors.
      SETTING: The Human Appetite Research Unit at Leeds University Psychology
      Department. SUBJECTS: Twelve dietary restrained females, normal weight and
      regular exercisers INTERVENTIONS: A control (rest) and a bout of high intensity
      exercise (cycling 50 min., 70% VO2 max.) was followed by a free-selection lunch
      comprising high-fat (HF) or low-fat (LF) foods. Hunger and heart rate profiles
      were tracked. Energy Intake (EI) was monitored in the laboratory throughout the
      day. Post-meal hedonic ratings were completed after lunch and dinner. RESULTS:
      There was a significant effect of lunch type (HF vs LF) on EI following exercise
      and rest (P < 0.001) and on total 24 h EI (P < 0.05): EI increased during both HF
      conditions compared to the LF. A main effect of exercise on tastiness and
      pleasantness (P < 0.05) of the LF foods served at lunch was found. However, there
      was no effect of exercise on hunger, weight or energy value of food eaten.
      CONCLUSIONS: Exercise raises the perceived pleasantness of foods in dietary
      restrained women, but does not increase the drive to eat within 8 h of the
      cessation of exercise. The combination of physical activity and a low-fat diet
      could be used advantageously to control appetite, prevent overconsumption and
      protect against the development of obesity.

PMID- 9578344
TI  - Delayed percutaneous transluminal coronary angioplasty after acute myocardial
      infarction.
AB  - The value of delayed percutaneous transluminal coronary angioplasty (> 12 h from
      admission or after thrombolytic therapy) following acute myocardial infarction is
      controversial. We compared the short- and long-term prognosis of 1940 consecutive
      patients after acute myocardial infarction, of whom 188 underwent delayed
      percutaneous transluminal coronary angioplasty. Delayed percutaneous transluminal
      coronary angioplasty was more frequently done in patients treated with
      thrombolysis (12%) than among patients excluded from thrombolytic therapy (8%;
      P=0.005). Patients in the delayed percutaneous transluminal coronary angioplasty
      group were younger, included more men and smokers and had less in-hospital
      complications in comparison to patients who did not undergo delayed percutaneous
      transluminal coronary angioplasty. The crude 30-day and 1-year mortality rates
      were 3 and 6% among patients who underwent percutaneous transluminal coronary
      angioplasty vs. 14 and 21% (P<0.01 for each) among those without percutaneous
      transluminal coronary angioplasty, respectively. After multivariate analysis
      adjusted for confounding factors, delayed percutaneous transluminal coronary
      angioplasty was associated with 65 (RR=0.35; 90% CI 0.14-0.88) and 50% (RR=0.50;
      90% CI 0.27-0.92) mortality risk reduction after 30 days and 1 year,
      respectively. In conclusion, delayed percutaneous transluminal coronary
      angioplasty applied to selected post-myocardial infarction patients upon clinical
      indication is safe and beneficial for the treatment of acute myocardial
      infarction in the community.

PMID- 9578345
TI  - Clinical implications of isolated double aortic arch and its complex with
      intracardiac anomalies.
AB  - From July 1, 1989 to June 30, 1996, a total of six patients, four male and two
      female, with double aortic arch (DAA) were registered. They aged 16 days to 6.5
      years. There were two patients with isolated DAA, and four complicated with
      intracardiac anomalies. All six patients presented respiratory distress and
      feeding problem early in life. However, cyanosis, owing to decreased pulmonary
      blood flow, predominated the clinical picture in each patient having DAA
      intricated with tetralogy of Fallot (TOF) and pulmonary stenosis, TOF with absent
      pulmonary valve syndrome, and type II-A tricuspid atresia. DiGeorge syndrome was
      documented in one patient with TOF and pulmonary stenosis. Expiratory wheezing
      was remarkable in the patient with TOF and absent pulmonary valve syndrome. Mild
      cyanosis and heart failure was noted in one patient with ventricular septal
      defect (VSD), and bicuspid pulmonary valve with mild valvular stenosis. Barium
      esophagogram showed indentations on esophagus in five patients. Echocardiography
      was yielding in three infants. Four patients, two isolated and two complex DAA,
      survived the surgical division of the smaller left aortic arch. One-stage and two
      stage operation was performed in patients having DAA intricated with VSD and TOF,
      respectively. The other two patients with complex DAA remained in close
      observation owing to the tolerance of symptoms related to intracardiac anomalies.

PMID- 9578346
TI  - Coronary artery disease: changes of blood lymphocyte subsets induced by physical
      exercise.
AB  - To examine the changes in the absolute numbers of blood lymphocyte subsets in
      patients with coronary artery disease, we studied 26 patients with documented
      coronary artery disease (group I) and 15 other subjects (group II) with atypical
      complaints and negative exercise test who served as controls. Blood lymphocyte
      subsets were determined at rest, immediately and 24 h after a bicycle exercise
      test. In both groups the absolute number of leukocytes/mm3 and lymphocytes/mm3
      was significantly greater immediately after exercise than at rest and returned to
      baseline values by 24 h post-exercise. The absolute number of B-lymphocytes and
      CD8+ T-lymphocytes did not change significantly in both groups, while CD3+ and
      CD4+ T-lymphocytes as well as CD25+ activated T-lymphocytes declined
      insignificantly immediately after exercise but increased significantly 24 h after
      exercise in both groups, with a higher increase (P<0.01) in all three variables
      under study (CD3+, CD4+ and CD25+ T-lymphocytes) in group I in comparison to
      group II (P<0.05). Our findings showed that changes in lymphocyte subsets induced
      by physical exercise differ between patients with and without documented coronary
      artery disease, suggesting that an alteration in immune function may account for
      these differences.

PMID- 9578347
TI  - Continuous administration of insulin-like growth factor-I and basic fibroblast
      growth factor does not affect left ventricular geometry after acute myocardial
      infarction in rats.
AB  - We examined the long-term effect of exogenous administration of bFGF and IGF-I on
      myocardial geometry in 72 Sprague-Dawley male rats subjected to AMI. A preloaded
      miniature osmotic pump subsequently implanted in the peritoneum for continuous
      infusion (1 week) of IGF-I, bFGF, IGF-I+bFGF or rat albumin. Six weeks following
      AMI the rats were killed and cross-section slices were analyzed for left
      ventricular geometry. No differences were observed between IGF-I-treated, bFGF
      treated, IGF-I+bFGF-treated and control groups in all parameters of the left
      ventricle.

PMID- 9578348
TI  - Effects of des-Asp-angiotensin I on experimentally-induced cardiac hypertrophy in
      rats.
AB  - We studied the effects of des-Asp-angiotensin I, a nine amino acid peptide, on
      cardiac hypertrophy caused by coarctation of the abdominal aorta in Sprague
      Dawley rats. The nonapeptide was effective when given either intravenously or
      orally. Maximum attenuation was observed with an i.v. dose of 153 pmol/day for 4
      days, and an oral dose of 250 nmol/day for 4 days. Three mg p.o. losartan, an
      angiotensin AT1 receptor antagonist, produced comparable attenuation. However,
      the attenuation produced by des-Asp-angiotensin I but not by losartan was blunted
      by 30.4 micromol of indomethacin. The oral efficacy of the nonapeptide was partly
      due to its low effective i.v. doses which were in the nM range. This range is
      below the Km of most enzymes including those of the intestinal peptidases (the Km
      of most enzymes is in the microM range). However, the mechanism of absorption of
      the peptide from the GIT into the systemic circulation remains to be
      investigated. The findings demonstrate for the first time, the anti-cardiac
      hypertrophic action of an angiotensin peptide. Unlike the ACE inhibitors and
      angiotensin receptor antagonists, the nonapeptide acts as an agonist on an
      indomethacin-sensitive angiotensin receptor to exert its action.

PMID- 9578349
TI  - Left ventricular hypertrophy and its relation to the cardiac kinin-forming system
      in hypertensive and diabetic rats.
AB  - We investigated the cardiac tissue kallikrein and kininogen levels, left
      ventricular wall thickness and mean arterial blood pressure of Wistar Kyoto and
      spontaneously hypertensive rats with and without streptozotocin-induced diabetes.
      The mean arterial blood pressure was highly elevated (P<0.001) in Wistar Kyoto
      diabetic and spontaneously hypertensive diabetic rats as compared with their
      respective controls. The cardiac tissue kallikrein and kininogen levels were
      reduced significantly (P<0.001) in diabetic Wistar Kyoto, spontaneously
      hypertensive and diabetic spontaneously hypertensive compared with Wistar Kyoto
      control rats. In addition, the left ventricular thickness was found to be
      increased (P<0.001) in diabetic Wistar Kyoto and spontaneously hypertensive rats
      in the presence and in the absence of diabetes. Our results indicate that reduced
      activity of the kinin-forming system may be responsible for inducing left
      ventricular hypertrophy in the presence of raised mean arterial blood pressure in
      diabetic and hypertensive rats. Thus, the kinin-forming components might have a
      protective role against the development of left ventricular hypertrophy. The
      possible significance of these findings is discussed.

PMID- 9578350
TI  - Monocyte activation in congestive heart failure due to coronary artery disease
      and idiopathic dilated cardiomyopathy.
AB  - OBJECTIVE: To investigate plasma tumor necrosis factor (TNF)alpha, tumor necrosis
      factor alpha soluble receptor I, interleukin-1beta and neopterin concentrations
      as markers of monocyte activation in patients with heart failure. STUDY DESIGN:
      The group consisted of patients with heart failure due to dilated cardiomyopathy
      (n=19) and coronary artery disease (n=11). Patients without cardiac failure
      served as controls (n=10). RESULTS: TNFalpha concentrations were elevated only in
      heart failure patients with coronary artery disease (2.9+/-0.3 pg/ml versus 1.7+/
      0.3 pg/ml; P<0.05). When the patients were grouped according to acute and chronic
      failure, TNFalpha concentrations were significantly elevated in acute failure
      (3.1+/-0.4 pg/ml, n=6 versus 1.7+/-0.2 pg/ml, n=8; P<0.05). TNFalpha
      concentrations were elevated in patients with coronary artery disease and chronic
      heart failure compared to coronary artery disease patients without failure (2.0+/
      0.4 pg/ml, n=6 versus 1.8+/-0.3 pg/ml, n=7; P<0.05). A higher proportion of
      patients with myocardial insufficiency showed increased lipopolysaccharide
      inducible TNFalpha concentrations (10/30 versus 0/9, P<0.05). CONCLUSIONS:
      TNFalpha is elevated in patients with acute cardiac decompensation. Among
      patients with chronic heart failure only those with coronary artery disease
      exhibit increased levels. Cytokine concentrations are similar in heart failure
      due to dilated cardiomyopathy and coronary artery disease. Monocytes of patients
      suffering from cardiac insufficiency show an increased sensitivity towards
      stimuli such as lipopolysaccharides.

PMID- 9578351
TI  - Ultrasound-guided compression of femoral pseudoaneurysm: an audit of practice.
AB  - OBJECTIVE: To audit the practice of ultrasound-guided compression of femoral
      pseudoaneurysm in a specialist cardiac hospital. BACKGROUND: Femoral
      pseudoaneurysm is an important complication of invasive cardiac procedures. This
      may require surgical repair but more recently ultrasound-guided compression for
      ablating pseudoaneurysms has been described. We investigated the success of such
      a procedure. METHODS AND RESULTS: In a 26-month period, 56 patients were referred
      for ultrasound scanning to exclude the formation of a femoral pseudoaneurysm
      following transfemoral cardiac procedures. During this period, 5756 diagnostic
      cardiac catherisations and 1165 coronary angioplasties were performed in our
      hospital (total of 6921 procedures). Of the 56 patients, 20 patients (0.3% of
      6921) were found to have a pseudoaneurysm. Ultrasound-guided compression was
      attempted in 11 patients and was successful in 7 patients (64%). Of the patients
      who had failed ultrasound-guided compression, 2 proceeded to surgical closure and
      2 were treated conservatively with compression stockings to facilitate thrombosis
      of the pseudoaneurysm. Of those who did not have an attempted ultrasound-guided
      compression of the pseudoaneurysm (n=9), a conservative approach consisting of
      resting the leg was adopted to facilitate spontaneous thrombosis of the
      pseudoaneurysm; repeat ultrasound scanning was needed for follow-up and 1 patient
      required surgical closure in this group. CONCLUSIONS: In patients with a femoral
      pseudoaneurysm following an invasive cardiac procedure, ultrasound-guided
      compression may be useful as an immediate step to ablate the pseudoaneurysm. This
      avoids either prolonged leg rest and repeated ultrasound scanning or surgical
      intervention. However, ultrasound-guided compression is not always successful; in
      these patients, a period of conservative management with repeat ultrasound
      scanning is appropriate to allow for the possible spontaneous thrombosis of the
      pseudoaneurysm. Surgical closure is needed in those patients whose pseudoaneurysm
      is enlarging, painful or remain patent.

PMID- 9578352
TI  - Cardiac myxomas: clinical and echocardiographic profile.
AB  - We reviewed our clinical and echocardiographic experience in 70 consecutive
      patients with 73 cardiac myxomas, diagnosed over an 11 year period. There were 21
      males and 49 females, ages ranged from 18 to 80 years. Only in 5.7% cases was the
      diagnosis of myxomas made clinically. 88.6% cases were initially diagnosed as
      having: mitral valve disease (70%), tricuspid valve disease (10%), ischemic heart
      disease (5.7%), cardiomyopathy (2.9%), and the remaining 5.7% were detected
      during family screening and follow-up. The mean duration of symptoms was 10.6
      months. The commonest symptom was dyspnoea (80%), followed by constitutional
      symptoms (45.7%), embolization (30%), palpitation (25.7%), syncope (15.7%), pedal
      oedema (15.7%) and pain chest (12.9%). The sites of myxomas were as follows: left
      atrium, 58; right atrium, 9; and, biatrium, 3. All myxomas except 3 were attached
      to the interatrial septum. The site, size, shape, attachment, mobility, prolapse
      into ventricle, and surface characteristic of myxomas were accurately assessed by
      2D-echocardiography and confirmed in all (65 of 70) who underwent surgery. When
      the morphological characteristic of myxomas were studied and correlated with
      clinical features large left atrial myxoma size was closely related with
      constitutional symptoms, congestive heart failure, with syncope and auscultatory
      findings suggestive of mitral valve disease, whereas smaller myxoma size and
      irregular surface were associated with embolization. Constitutional symptoms were
      only present in left atrial myxoma. Post-operative mean echocardiographic follow
      up of 60 months showed no recurrence except in 2 with familial myxoma. We
      conclude that the majority of myxomas mimic many cardiovascular diseases and were
      detected in symptomatic patients, so a high index of clinical suspicion is
      important for its early and correct diagnosis. The size and appearance of the
      myxomas correlated with the presenting symptoms.

PMID- 9578353
TI  - Are insulin metabolism and night-time blood pressure related to left ventricular
      hypertrophy?
AB  - Essential hypertensives in whom blood pressure does not fall during sleep (non
      dippers) are thought to be at greater risk of cardiovascular morbidity. Insulin
      resistance is also suggested to be a risk factor for cardiovascular morbidity.
      The purpose of the present study was to evaluate the relationship of insulin
      metabolism to left ventricular hypertrophy in dippers and non-dippers. Thirty
      male, non-diabetic out-patients with newly diagnosed arterial hypertension were
      included in the study: 21 dippers (mean age 45+/-13 years; body mass index 28.2+/
      4.0 kg/m2) and nine non-dippers (mean age 48+/-10 years, body mass index 28.6+/
      3.9 kg/m2). Patients were subdivided into dippers and non-dippers on the basis of
      24-h ambulatory blood pressure monitoring. Insulin and glucose responses to an
      oral glucose load have been evaluated. C-peptide levels were determined. Left
      ventricular mass was assessed by echocardiography. Non-dippers had significantly
      higher mean night-time systolic (non-dippers: 148+/-9; dippers: 123+/-16 mmHg;
      P<0.001), diastolic blood pressure (non-dippers: 90+/-8; dippers: 77+/-8 mmHg;
      P<0.001) and non-significantly higher left ventricular mass (279+/-92 g) and left
      ventricular mass index (135+/-46 g/m2). No significant difference was found
      between C-peptide, insulin, glucose levels and incremental areas between the two
      groups. Night-time blood pressure, insulin, C-peptide and glucose did not
      correlate with left ventricular mass in non-dippers. Dippers showed a positive
      correlation between fasting C-peptide and left ventricular mass (r=0.48, P=0.02)
      and between glucose and left ventricular mass (r=0.42, P=0.05). Our data indicate
      that night-time blood pressure and insulin are not related to left ventricular
      hypertrophy in patients with essential hypertension.

PMID- 9578354
TI  - Cardiac arrhythmias during two different stages of the menstrual cycle.
AB  - We have frequently observed that female patients report an association between
      their arrhythmias and their menstrual period but little is known about such an
      association. We studied 25 female patients 25.9+/-7.3 year-old with regular
      menstrual periods. Thirteen patients were evaluated because they suffered from
      cardiac symptoms and complained of arrhythmia aggravation during their menstrual
      period. Twelve normal female patients formed the control group. The evaluation
      was performed in a drug-free state. All the patients had a 24-h Holter study
      performed during the 7th day of their menstrual cycle and 3 days before the
      following menstrual period. No patient had sustained arrhythmia during the
      monitoring periods. When comparing the two Holter recordings we did not find
      statistically significant differences with respect to either the total count of
      supraventricular and ventricular premature beats or the heart rate.

PMID- 9578355
TI  - Exercise-induced changes in the QT interval duration and dispersion in patients
      with sudden cardiac death after myocardial infarction.
AB  - BACKGROUND: Prolongation of the QT interval and increased QT dispersion have been
      proposed to be associated with arrhythmic risk after myocardial infarction.
      However, controversy remains regarding the prognostic value of ventricular
      repolarization abnormalities in the risk stratification of patients surviving
      acute myocardial infarction. HYPOTHESIS AND OBJECTIVE: The QT interval is
      sensitive to myocardial ischaemia, and exercise-induced ischaemia may change the
      QT interval regionally, resulting in increased QT dispersion. This study examined
      whether there are abnormalities of ventricular repolarization during exercise and
      whether assessment of the exercise-induced changes in QT interval duration and
      dispersion would be able to differentiate patients at high risk from those at low
      risk of sudden cardiac death after myocardial infarction. METHODS: Twenty-six
      post-myocardial infarction patients (mean age 54.5+/-8.9 years, 22 men) were
      retrospectively studied. Thirteen patients who died suddenly (SCD patients)
      during a follow-up of 39+/-6 months were compared to 13 patients who remained
      event-free, i.e. no ventricular tachyarrhythmias, no reinfarction, no by-pass (MI
      survivors). The two groups were pair-matched for age, gender, site of infarction,
      left ventricular ejection fraction and use of beta blocker. A further 13 patients
      with chest pain, normal coronary arteriograms and negative exercise test results
      were studied as controls. They were age and gender matched with the post
      infarction patients. A 12-lead exercise ECG was recorded from each patient
      before, during and after exercise. QT and RR interval were measured on the
      exercise ECGs at each stage and QT dispersion was defined as the difference
      between the maximum and minimum QT intervals across the 12-lead ECG. RESULTS:
      There were no significant differences in RR, QT and QTc (Bazett's and
      Fridericia's correction) intervals, or QT dispersion between any groups before
      exercise. A significant difference in QT and QT dispersion was found at peak
      exercise between post-infarction patients and controls (P=0.03 and P=0.0001,
      respectively), but no difference was observed between SCD patients and MI
      survivors. The maximum QTc at peak exercise was longer in SCD patients compared
      with MI survivors (P=0.02) and a maximum QTc>440 ms (Bazett's correction) was
      common in SCD patients but not in MI survivors or controls (62%, 15%, 15%,
      P=0.01). The differences in QT, QTc or QT dispersion observed at peak exercise
      were no longer significant after exercise. CONCLUSIONS: Exercise-induced
      prolongation of the QTc interval differentiates patients at high risk of sudden
      cardiac death from those at low risk, whereas exercise-induced changes in QT
      dispersion failed to identify patients at high risk of sudden cardiac death after
      myocardial infarction.

PMID- 9578356
TI  - Dispersion of repolarization in paroxysmal atrial fibrillation.
AB  - Widened dispersion of refractoriness has been considered to lead to an increase
      in atrial vulnerability. In this study, we obtained simultaneous monophasic
      action potential recordings by 2 special catheters from 2 different loci in the
      right atrium in 9 normal subjects (Group 1) and in 7 patients with paroxysmal
      atrial fibrillation (Group 2). We measured action potential duration at 50%
      (APD50) and 90% (APD90) repolarization from both loci in the right atrium during
      steady-state through one of the two catheters. The differences between APD50 and
      APD90 recorded by the two catheters were designated as dispersion of APD50 and
      dispersion of APD90, respectively. While, the mean APD50 and APD90 were 149.7+/
      16.9 and 228.3+/-44.7 ms respectively in Group 1, the corresponding values for
      Group 2 were 145.7+/-33.5 and 213.5+/-53.1 ms. The difference between the 2
      groups was not statistically significant. However, the dispersion of APD50 and
      APD90 were 13.8+/-13.8 and 10.0+/-9.7 ms in Group 1 and 42.8+/-19.6 and 57.1+/
      32.4 in Group 2, respectively and the difference between the 2 groups for both
      measurements was statistically significant (P<0.01). Another finding was a high
      correlation between age and dispersion of APD90 in the whole population studied
      (r=0.82, P<0.001). With these findings, although one can not derive the
      conclusion that patients with paroxysmal atrial fibrillation have a greater
      dispersion of repolarization, our finding of increasing dispersion of
      repolarization with age could be an explanatory factor for the increased
      prevalence of atrial fibrillation with advanced age.

PMID- 9578357
TI  - Survey of rheumatic heart disease in school children of Kinshasa town.
AB  - STUDY OBJECTIVE: To determine the prevalence of rheumatic heart disease and study
      the association of this disease to factor such as personal host and environment.
      DESIGN: A cross sectional survey was carried out by a specially trained medical
      team. SETTING: The study involved high risk school children aged 5-16 years from
      Binza-Kinshasa urban area and adjoining slums in semi-urban area of Kinshasa
      town. METHODS: A total of 4848 children randomly selected on the list of semi
      urban and urban schools and representing 10% of the schools population were
      included in the survey with clinical echocardiographic examinations. RESULTS: Of
      the 4848 children screened, prevalence of rheumatic heart disease was 14.03/1000.
      The prevalence was significantly greater in slums schools (22.2/1000) than in
      urban school (4/1000). In slums area, the mitral valve was the valve most
      commonly affected by rheumatic heart disease. Risk factors such as birth in rainy
      season (RR=2.2), low birth weight (RR=1.81), low socioeconomic status (RR=2.68),
      malnutrition<mean BMI-1 SD (RR=2.64), crowding>8 persons/household (RR=4.10) and
      migrant status (RR=4.79) predicted significantly rheumatic heart disease
      occurrence in children living in the semi-urban area (slums). Only birth in rainy
      season (RR=3.24) predicted significantly rheumatic heart disease onset in
      children having residence in the urban area. CONCLUSIONS: Rheumatic heart disease
      runs a more severe course in Kinshasa, because appropriate medical care, sanitary
      conditions, primary and secondary prophylaxis are not available. Echocardiograpy
      is necessary to identify cases of rheumatic heart disease.

PMID- 9578358
TI  - Systolic and diastolic blood pressure related to six other risk parameters in
      Turkish adults: strong correlation with relative weight.
AB  - This study aimed to investigate the relationship of systolic and diastolic blood
      pressure (BP) with a series of metabolic and nonmetabolic cardiovascular risk
      variables in a random sample of Turkish general adult population. Values of
      systolic and diastolic BP on the one hand and of six variables including body
      mass index (BMI), waist/hip ratio (W/H), grade of physical activity (PhA), plasma
      lipids and cigarette smoking from 1046 men and 1095 women aged 225 years were
      included in the analysis. Participants were classified into tertiles according to
      systolic and diastolic BP measurements, and were stratified in two age
      categories: 25-44 years (young) and 45-74 years (elderly). Plasma total
      cholesterol and triglyceride (Trg) concentrations were measured by the enzymatic
      method with the Reflotron apparatus. In multiple regression analysis, age proved
      the strongest independent determinant of BP. BMI was a strong independent marker
      of systolic and diastolic pressures in women, while in men the determinant value
      of the W/H was equivalent to BMI. For each increment of 1 kg/m2 of BMI was
      associated in men an increase of over 8 and 16 mmHg in diastolic and systolic
      pressure, respectively, regardless of age group. Corresponding figures in women
      were roughly 6 and 10 mmHg. Though plasma Trg were not independently associated
      with BP in either gender, the independent contribution of plasma cholesterol
      level in women to systolic and diastolic pressures was small but significant. BP
      was related to mean concentrations of plasma Trg in young adults only, total
      cholesterol levels were associated with diastolic pressure in young men only,
      whereas PhA grade was not associated with BP. These findings are consistent with
      the theory that, in the normal state, functions such as regulation of BP, body
      weight and lipid metabolism are closely linked to each other.

PMID- 9578359
TI  - Recurrent myocardial infarction caused by a giant coronary aneurysm.
AB  - We report on a patient with a giant aneurysm arising from the right coronary
      artery leading to infarction due to a steal phenomenon. Emergency coronary
      angiography was performed. The orifice of the aneurysm was occluded by balloon
      catheter restoring blood flow and resolving ischemia. Aneurysmectomie was done
      subsequently. The patient recovered very soon, and the following course was
      uneventful. This case illustrates that occasionally causes other than usual
      coronary atherosclerosis may lead to acute coronary syndromes.

PMID- 9578360
TI  - A soccer victim: late rupture of the ascending aorta after violent physical
      trauma.
AB  - A 56-year-old man without previous medical history or risk factors for coronary
      artery disease, presented with chest pain 2 weeks after violent blunt chest
      trauma. He was as a spectator, beaten and kicked almost to death during an
      amateur soccer match. Because of embarrassment, this was denied till shortly
      after his death. Shortly before the patient died, thoracic CT-scan showed a
      dissecting aneurysm of the ascending aorta in association with pericardial and
      bilateral pleural effusion. He suddenly died in-hospital due to heart tamponade
      secondary to rupture of the aneurysm into the pericardial space. At autopsy, the
      intimal layer of the aorta showed no atherosclerotic changes. The intimal rupture
      was located just above the origin of the right coronary artery.

PMID- 9578361
TI  - Combined mitral and aortic valvuloplasty by antegrade transseptal approach using
      Inoue balloon catheter.
AB  - OBJECTIVE: The purpose of this paper is firstly to highlight the ease with which
      the antegrade balloon aortic valvuloplasty can be performed with the Inoue
      balloon and secondly, the utility of the Inoue rubber nylon self-positioning
      balloon catheter used for twin valve dilatation. STUDY DESIGN: Percutaneous
      balloon valvuloplasty is being increasingly practised for treatment of
      multivalvular stenoses. We describe the case of a young (21 years), male who
      successfully underwent combined dilation of rheumatic mitral and aortic stenosis
      via the transseptal antegrade approach using Inoue balloon catheters for both
      valves. RESULT: Following the procedure, the mitral valve area increased from 0.6
      cm2 to 1.7 cm2 and the peak systolic gradient across the aortic valve decreased
      from 100 mm Hg to 8 mm Hg without causing significant regurgitation at either.
      CONCLUSIONS: This report highlights the ease of performing balloon aortic
      valvuloplasty via the antegrade transvenous route and utilizing the advantages of
      Inoue balloon catheter.

PMID- 9578362
TI  - Acute renal failure due to mechanical haemolysis after percutaneous catheter
      occlusion of a patent arterial duct.

PMID- 9578363
TI  - Muscle performance--fatigue, recovery and trainability.

PMID- 9578364
TI  - The Na+,K+ pump and muscle excitability.
AB  - In most types of mammalian skeletal muscles the total concentration of Na+,K+
      pumps is 0.2-0.8 nmol g wet wt(-1). At rest, only around 5% of these Na+,K+ pumps
      are active, but during high-frequency stimulation, virtually all Na+,K+ pumps may
      be called into action within a few seconds. Despite this large capacity for
      active Na+,K+ transport, excitation often induces a net loss of K+, a net gain of
      Na+, depolarization and ensuing loss of excitability. In muscles exposed to high
      [K+]o or low [Na+]o, alone or combined, excitability is reduced. Under these
      conditions, hormonal or excitation-induced stimulation of the Na+,K+ pump leads
      to considerable force recovery. This recovery can be blocked by ouabain and seems
      to be the result of Na+,K+ pump induced hyperpolarization and restoration of
      Na+,K+ gradients. In muscles where the capacity of the Na+,K+ pump is reduced,
      the decline in the force developing during continuous electrical stimulation (30
      90 Hz) is accelerated and the subsequent force recovery considerably delayed. The
      loss of endurance is significant within a few seconds after the onset of
      stimulation. Increased concentration of Na+ channels or open-time of Na+ channels
      is also associated with reduced endurance and impairment of force recovery. This
      indicates that during contractile activity, excitability is acutely dependent on
      the ratio between Na+ entry and Na+,K+ pump capacity. Contrary to previous
      assumptions, the Na+,K+ pump, due to rapid activation of its large transport
      capacity seems to play a dynamic role in the from second to second ongoing
      restoration and maintenance of excitability in working skeletal muscle.

PMID- 9578365
TI  - The regulation of the Na+,K+ pump in contracting skeletal muscle.
AB  - Increased passive Na+,K+ fluxes necessitate an efficient activation of the Na+,K+
      pump in working muscles to limit the rundown of the Na+,K+ chemical gradients and
      ensuing loss of excitability. Several studies have demonstrated an increase in
      Na+,K+-pump rate in working muscles, and in electrically stimulated muscles up to
      a 22-fold increase in active Na+,K+ transport has been observed. Excitation
      induced increase in intracellular Na+ is believed to be the primary stimulus for
      Na+,K+ pumping in a contracting muscle. In muscles recovering from electrical
      stimulation, however, the activity of the pump may stay elevated even after
      intracellular Na+ has been reduced to below the resting level. Moreover, in rat
      soleus muscles 10-s stimulation at 60 Hz induced a 5-fold increase in the
      activity of the Na+,K+ pump although mean intracellular [Na+] was unchanged.
      These findings strongly suggest that a substantial part of the excitation-induced
      increase in Na+,K+-pump activity is caused by mechanisms other than increased
      intracellular [Na+]. The mechanism behind this activation is not clear, but may
      involve a change in the affinity of the Na+,K+ pump for intracellular Na+. In
      addition to intracellular [Na+], the Na+,K+ pump may be stimulated in contracting
      muscles by other factors such as catecholamines, calcitonin gene-related peptide
      (CGRP), free fatty acids and cytoskeletal links. Together, this activation may
      form a feed forward mechanism protecting muscles from loss of excitability during
      periods of contraction by increasing Na+,K+-pump activity prior to erosion of the
      Na+,K+ chemical gradients. During exercise of high intensity, however,
      intracellular [Na+] increases substantially constituting an additional stimulus
      for the pump.

PMID- 9578366
TI  - Cation pumps in skeletal muscle: potential role in muscle fatigue.
AB  - Two membrane bound pumps in skeletal muscle, the sarcolemma Na+-K+ adenosine
      triphosphatase (ATPase) and the sarcoplasmic reticulum Ca2+-ATPase, provide for
      the maintenance of transmembrane ionic gradients necessary for excitation and
      activation of the myofibrillar apparatus. The rate at which the pumps are capable
      of establishing ionic homeostasis depends on the maximal activity of the enzyme
      and the potential of the metabolic pathways for supplying adenosine triphosphate
      (ATP). The activity of the Ca2+-ATPase appears to be expressed in a fibre type
      specific manner with both the amount of the enzyme and the isoform type related
      to the speed of contraction. In contrast, only minimal differences exist between
      slow-twitch and fast-twitch fibres in Na+-K+ ATPase activity. Evidence is
      accumulating that both active transport of Na+ and K+ across the sarcolemma and
      Ca2+-uptake by the sarcoplasmic reticulum may be impaired in vivo in a task
      specific manner resulting in loss of contractile function. In contrast to the
      Ca2+-ATPase, the Na+-K+ ATPase can be rapidly upregulated soon after the onset of
      a sustained pattern of activity. Similar programmes of activity result in a
      downregulation of Ca2+-ATPase but at a much later time point. The manner in which
      the metabolic pathways reorganize following chronic activity to meet the changes
      in ATP demand by the cation pumps and the degree to which these adaptations are
      compartmentalized is uncertain.

PMID- 9578367
TI  - Skeletal muscle fatigue in normal subjects and heart failure patients. Is there a
      common mechanism?
AB  - Skeletal muscle fatigue develops gradually during all forms of exercise, and
      develops more rapidly in heart failure patients. The fatigue mechanism is still
      not known, but is most likely localized to the muscle cells themselves. During
      high intensity exercise the perturbations of the Na+ and K+ balance in the
      exercising muscle favour depolarization, smaller action potentials and
      inexcitability. The Na+, K+ pump becomes strongly activated and limits, but does
      not prevent the rise in extracellular Na+, K+ pump concentration and
      intracellular Na+ concentration. However, by virtue of its electrogenic property
      the pump may contribute in maintaining excitability and contractility by keeping
      the cells more polarized than the ion gradients predict. With prolonged exercise
      perturbations of Na+ and K+ are smaller and fatigue may be associated with
      altered cellular handling of Ca2+ and Mg2+. Release of Ca2+ from the sarcoplasmic
      reticulum (SR) is reduced in the absence of changes of the cellular content of
      Ca2+ and Mg2+. In heart failure several clinical reports indicate severe
      electrolyte perturbations in skeletal muscle. However, in well controlled studies
      small or insignificant changes are found. We conclude that with high intensity
      exercise perturbations of Na+ and K+ in muscle cells may contribute to fatigue,
      whereas with endurance type of exercise and in heart failure patients the
      skeletal muscle fatigue is more likely to reside in the intracellular control of
      Ca2+ release and reuptake.

PMID- 9578368
TI  - Events of the excitation-contraction-relaxation (E-C-R) cycle in fast- and slow
      twitch mammalian muscle fibres relevant to muscle fatigue.
AB  - The excitation-contraction-relaxation cycle (E-C-R) in the mammalian twitch
      muscle comprises the following major events: (1) initiation and propagation of an
      action potential along the sarcolemma and transverse (T)-tubular system; (2)
      detection of the T-system depolarization signal and signal transmission from the
      T-tubule to the sarcoplasmic reticulum (SR) membrane; (3) Ca2+ release from the
      SR; (4) transient rise of myoplasmic [Ca2+]; (5) transient activation of the Ca2+
      regulatory system and of the contractile apparatus; (6) Ca2+ reuptake by the SR
      Ca2+ pump and Ca2+ binding to myoplasmic sites. There are many steps in the E-C-R
      cycle which can be seen as potential sites for muscle fatigue and this review
      explores how structural and functional differences between the fast- and slow
      twitch fibres with respect to the E-C-R cycle events can explain to a great
      extent differences in their fatiguability profiles.

PMID- 9578369
TI  - New evidence for similarities in excitation-contraction coupling in skeletal and
      cardiac muscle.
AB  - This review describes several new experimental observations indicating that some
      of the differences thought to distinguish activation of contraction in skeletal
      and cardiac muscle may be in fact much less profound than are currently
      considered. Three such areas are considered in particular. First, it now appears
      that activation of the elementary units of Ca2+ release from the sarcoplasmic
      reticulum ('Ca2+ sparks') in skeletal muscle may occur not only as the result of
      voltage activation but also of Ca2+ activation in a process very much like Ca2+
      induced Ca2+ release (CICR) in cardiac muscle. Second, there is new evidence that
      activation of contraction in cardiac muscle may be partly reliant on a voltage
      sensitive release mechanism (VSRM) similar to that in skeletal muscle. Third,
      digitalis binds to a high affinity site on the cardiac sarcoplasmic reticulum
      Ca2+ release channel (ryanodine receptor RyR) causing an increase in single
      channel open probability which could contribute to its positive inotropic action;
      although mammalian skeletal muscle does not appear to share this sensitivity to
      cardiac glycosides, amphibian skeletal muscle has both cardiac and skeletal
      isoforms of the channel and does indeed demonstrate a positive inotropic action
      in response to digitalis. These results raise the possibility that several
      differences thought to represent 'fundamental' distinctions between the two
      muscle types and how they generate and regulate contraction, as well as
      pharmacological sensitivities, may be more similar than are currently considered.

PMID- 9578370
TI  - Mechanisms underlying the reduction of isometric force in skeletal muscle
      fatigue.
AB  - A decline of isometric force production is one characteristic of skeletal muscle
      fatigue. In fatigue produced by repeated short tetani, this force decline can be
      divided into two components: a reduction of the cross-bridges' ability to
      generate force, which comes early; and a reduction of the sarcoplasmic reticulum
      Ca2+ release, which develops late in fatigue. Acidification due to lactic acid
      accumulation has been considered as an important cause of the reduced cross
      bridge force production. However, in mammalian muscle it has been shown that
      acidification has little effect on isometric force production at physiological
      temperatures. By exclusion, in mammalian muscle fatigue, the reduction of force
      due to impaired cross-bridge function would be caused by accumulation of
      inorganic phosphate ions, which results from phosphocreatine breakdown. The
      reduction of sarcoplasmic reticulum Ca2+ release in late fatigue correlates with
      a decline of ATP and we speculate that the reduced Ca2+ release is caused by a
      local increase of the ADP/ATP ratio in the triads.

PMID- 9578371
TI  - Energy supply and muscle fatigue in humans.
AB  - Limitations in energy supply is a classical hypothesis of muscle fatigue. The
      present paper reviews the evidence available from human studies that energy
      deficiency is an important factor in fatigue. The maximal rate of energy
      expenditure determined in skinned fibres is close to the rate of adenosine
      triphosphate (ATP) utilisation observed in vivo and data suggest that performance
      during short bursts of exercise (<5 s duration) primarily is limited by other
      factors than energy supply (e.g. Vmax of myosine adenosine triphosphatase
      (ATPase), motor unit recruitment, engaged muscle mass). Within 10 s of exercise
      maximal power output decreases considerably and coincides with depletion of
      phosphocreatine. During recovery, maximal force and power output is restored with
      a similar time course as the resynthesis of phosphocreatine. Increases in muscle
      store of phosphocreatine through dietary supplementation with creatine increases
      performance during high-intensity exercise. These findings support the hypothesis
      that energy supply limits performance during high-intensity exercise. It is well
      documented that pre-exercise muscle glycogen content is related to performance
      during moderate intensity exercise. Recent data indicates that the interfibre
      variation in phosphocreatine is large after prolonged exercise to fatigue and
      that some fibres are depleted to the same extent as after high-intensity
      exercise. Despite relatively small decreases in ATP, the products of ATP
      hydrolysis (Pi and free ADP) may increase considerably. Free ADP calculated from
      the creatine kinase reaction increases 10-fold both after high-intensity exercise
      and after prolonged exercise to fatigue. It is suggested that local increases in
      ADP may reach inhibitory levels for the contraction process.

PMID- 9578372
TI  - Possible effects of fatigue on muscle efficiency.
AB  - The efficiency of energy transduction is defined as the ratio of the work done by
      a muscle to the free energy change of the chemical processes driving contraction.
      Two examples of the experimental measurement of muscle efficiency are: (1) the
      classical method of Hill which measures the value during a steady state of
      shortening, (2) measuring the overall efficiency during a complete cycle of a
      sinusoidal process, which comes closer to the situation during natural
      locomotion. The reasons why fatigue might lower efficiency are the following. (1)
      The reduction in PCr concentration and increase in Pi and Cr concentration which
      are characteristic of fatigued muscle, reduce the free energy of PCr splitting.
      This will reduce the efficiency of the recovery process. It is not known whether
      the efficiency of the initial process is increased to compensate. (2) There is a
      general conflict between efficiency and power output when motor units are chosen
      for a task or when the timing of activation is decided. During fatigue more
      powerful units have to be used to achieve a task which is no longer within the
      scope of less powerful units. (3) The slowing of relaxation that is sometimes
      found with fatigue may make it impossible to achieve the short periods of
      activity required for optimum efficiency during rapid cyclical movements. A
      reason why fatigue might increase efficiency is that muscles are thought to be
      more efficient energy converters when not fully activated than when fully active.
      Full activation is often not achieved in muscle which is considerably fatigued.
      Available observations do not allow us to find where the balance between these
      factors lies. The conclusion is thus that experiments of both the types discussed
      here should be performed.

PMID- 9578373
TI  - Neural control in human muscle fatigue: changes in muscle afferents, motoneurones
      and motor cortical drive [corrected].
AB  - To understand the neural factors which contribute to fatigue, it is not
      satisfactory to regard fatigue as occurring only when a task can no longer be
      performed. Changes in muscle afferent feedback, motoneuronal discharge, motor
      cortical output, and perceived effort develop well before an endurance limit in
      limb muscles. During sustained maximal contractions the discharge of motoneurones
      declines, commonly to below the level required to produce maximal force from the
      muscle whose contractile speed is usually slowed. Thus, some 'central' fatigue
      develops. Recent findings using transcranial stimulation have revealed that the
      motor cortex is one site at which suboptimal output develops during human muscle
      fatigue. There is a need to study the reflex effects on motoneurones and the
      excitability of the motor cortex in experimental animals, as well as to apply
      rigorous methods to assess these processes in voluntary exercise in human
      subjects [corrected].

PMID- 9578374
TI  - Mechanisms underlying the slow recovery of force after fatigue: importance of
      intracellular calcium.
AB  - Recovery of force production after an intense bout of activity may sometimes take
      several days, especially at low activation frequencies ('low frequency fatigue').
      This slow recovery can also be observed in isolated muscle and single muscle
      fibres. The origin of the force deficit is failure of excitation-contraction
      coupling at the level of the triads. The most likely cause of the failure is an
      elevated intracellular Ca2+ level, but the site of action of Ca2+ is unclear.
      Available evidence does not support the involvement of Ca2+-activated proteases.
      Ca2+-induced damage to mitochondria or swelling of t-tubules do not seem to be
      causative factors. Other mechanisms are discussed, including possible detrimental
      effects of Ca2+-activated lipases, calmodulin, and reactive oxygen species.

PMID- 9578375
TI  - Regulation of GLUT4 protein and glycogen synthase during muscle glycogen
      synthesis after exercise.
AB  - The pattern of muscle glycogen synthesis following its depletion by exercise is
      biphasic. Initially, there is a rapid, insulin independent increase in the muscle
      glycogen stores. This is then followed by a slower insulin dependent rate of
      synthesis. Contributing to the rapid phase of glycogen synthesis is an increase
      in muscle cell membrane permeability to glucose, which serves to increase the
      intracellular concentration of glucose-6-phosphate (G6P) and activate glycogen
      synthase. Stimulation of glucose transport by muscle contraction as well as
      insulin is largely mediated by translocation of the glucose transporter isoform
      GLUT4 from intracellular sites to the plasma membrane. Thus, the increase in
      membrane permeability to glucose following exercise most likely reflects an
      increase in GLUT4 protein associated with the plasma membrane. This insulin-like
      effect on muscle glucose transport induced by muscle contraction, however,
      reverses rapidly after exercise is stopped. As this direct effect on transport is
      lost, it is replaced by a marked increase in the sensitivity of muscle glucose
      transport and glycogen synthesis to insulin. Thus, the second phase of glycogen
      synthesis appears to be related to an increased muscle insulin sensitivity.
      Although the cellular modifications responsible for the increase in insulin
      sensitivity are unknown, it apparently helps maintain an increased number of
      GLUT4 transporters associated with the plasma membrane once the contraction
      stimulated effect on translocation has reversed. It is also possible that an
      increase in GLUT4 protein expression plays a role during the insulin dependent
      phase.

PMID- 9578376
TI  - Muscle blood flow and oxygen uptake in recovery from exercise.
AB  - The metabolic and muscle blood flow response in recovery from exercise is
      dependent on the type and the duration of the exercise. Immediately after both
      intense static and dynamical exercise blood flow to the exercised muscles
      increases suggesting that blood flow is mechanically hindered by muscle
      contraction. After the initial rise (seconds) muscle blood flow decreases at a
      moderate rate and the time to reach resting flow levels varies from seconds to
      more than 30 min. It is unclear as to what causes the elevated blood flow during
      recovery. A mismatch between the time course of changes in blood flow and oxygen
      uptake suggests that the blood flow is not directly regulated by the need of
      oxygen in the exercised muscles. The hyperaemic response may be linked to locally
      released factors, such as ions and metabolites. However, the signal by which the
      blood flow is elevated remains unknown. After exercise both pulmonary and muscle
      oxygen uptake decrease rapidly, but can remain above resting levels for several
      hours. Resynthesis of substrates such as CP, ATP and glycogen cannot account for
      the entire excessive post-exercise oxygen uptake (EPOC) in the exercised muscles
      and the cause of the elevated muscle oxygen uptake in recovery from exercise
      remains to be assessed.

PMID- 9578377
TI  - Adrenergic control of post-exercise metabolism.
AB  - After strenuous exercise there is a sustained increase in resting O2 consumption.
      The magnitude and duration of the excess post-exercise O2 consumption (EPOC) is a
      function of exercise intensity and exercise duration. Some of the mechanisms
      underlying the rapid EPOC component (<1 h) are well defined, while the mechanisms
      causing the prolonged EPOC component (>1 h) are not fully understood. It has been
      suggested that beta-adrenergic stimulation is of importance for the prolonged
      component. There is an increased level of plasma adrenaline and noradrenaline
      during exercise, and it is shown that catecholamines stimulate energy expenditure
      through beta-adrenoceptors. After exercise an increased fat oxidation and an
      increased rate of triglyceride fatty acid (TG-FA) cycling may account for a
      significant part of the prolonged EPOC component. These processes may be
      stimulated by catecholamines. However, the return of plasma concentration of
      catecholamines to resting levels after exercise is more rapid than the return of
      O2 uptake. But plasma concentration of catecholamines may be an insensitive
      indicator of sympathetic activity, since the clearance rate of catecholamines is
      high. Also, the sensitivity to catecholamines may be increased after exercise. A
      decreased post-exercise O2 uptake has been shown when beta-blockade is
      administered in dogs before the exercise bout. In a pilot study in humans,
      administration of beta-antagonist after exercise did not seem to change EPOC.

PMID- 9578378
TI  - Recovery of the immune system after exercise.
AB  - In the recovery phase after intense exercise is found suppressed blood
      concentration of lymphocytes, suppressed natural immunity of blood lymphocytes,
      decreased concentration of secretory IgA in mucosa, but increased blood
      concentration of neutrophils and increased levels in the blood of inflammatory
      cytokines. Thus, after intense long-term exercise, the immune system is
      characterized by concomitant inflammation and temporary suppression of the
      cellular immune system, the most pronounced findings being 2-4 h after the
      exercise. The underlying mechanisms are multifactorial and include
      neuroendocrinological and metabolic factors. High levels of cytokines, especially
      interleukin-6, are found in the recovery period after eccentric exercise, and it
      has been demonstrated that a close association exists between muscle damage and
      increased levels of interleukin-6.

PMID- 9578379
TI  - Determination of muscle contractile properties: the importance of the nerve.
AB  - Contractile phenotype of muscle fibres is strongly influenced by hormones,
      stretch and influences from the motor neurones, although cell lineage probably
      also plays a role. Motor neurones can affect muscle fibres by releasing
      neurotrophic substances and by evoking electrical activity in the muscle. For
      regulating contractile properties such as speed, strength and endurance it has
      been demonstrated that electrical activity is crucial, while the role of putative
      neurotrophic substances remains unclear. The signal to change is coded in the
      pattern of electrical activity. Thus, high amounts of activity lead to slow
      shortening velocity and myosin heavy chains, while low amounts of activity lead
      to a fast phenotype. For regulation of twitch duration frequency also plays a
      role, and for preventing atrophy in denervated muscles high frequency seems to be
      beneficial, particularly in fast muscles. Little is known about the excitation
      adaptation pathway linking action potentials to expression of genes that are
      relevant for contractile properties. Muscle specific transcription factors of the
      helix-loop-helix family such as myoD and myogenin could be important for
      regulating genes related to metabolic profile and fibre size/strength, while
      their role in determining myosin heavy chain expression and classical fibre type
      is more uncertain.

PMID- 9578381
TI  - Glucose utilization during exercise: influence of endurance training.
AB  - During exercise skeletal muscle glucose utilization is higher than at rest. This
      is due to the combined effect of an increase in glucose supply, increased surface
      membrane glucose transport capacity and increased muscle glucose metabolism
      during exercise. The kinetics of glucose utilization in skeletal muscle during
      exercise in humans show an apparent Km of approximately 10 mM, indicating that
      changes in the blood glucose concentration around the physiological level of
      approximately 5 mM almost linearly translate into changes in muscle glucose
      utilization. The signalling events responsible for increased glucose transport in
      contracting muscle are not well understood, although calcium seems to be
      involved. Contractions do not utilize the proximal part of the insulin signalling
      cascade to activate glucose transport, because contractions do not cause
      phosphorylation of insulin receptor substrate 1 or activation of
      phosphatidylinositol 3-kinase. Endurance training leads to a decrease in glucose
      utilization during submaximal exercise of a given absolute submaximal power
      output in spite of a large increase in the total muscle GLUT4 content. The
      molecular mechanism behind this decrease in glucose utilization seems to be
      blunted exercise-induced translocation of GLUT4 protein to the sarcolemma, in
      turn blunting the exercise-induced increase in sarcolemmal glucose transport
      capacity.

PMID- 9578380
TI  - Molecular and cellular adaptation of muscle in response to physical training.
AB  - Molecular biology tools can be used to answer questions as to how adaptations
      occur in skeletal muscle with training that could provide new frameworks to
      improve physical performance. A number of mRNAs for transfer of metabolic
      substrates into muscle cells increase after a single bout of exercise
      demonstrating the responsiveness of some gene expression to exercise. In stretch
      induced hypertrophy SRE1 of the skeletal alpha-actin promoter is required to
      transactivate the promoter. Less retardation of SRF in crude nuclear extracts
      from the stretched muscle implies a conformational change in SRF because of the
      stretch. Transgenic animals will provide a tool to test questions concerned with
      how exercise signals adaptive changes in gene expression. Molecular biological
      approaches will be able to evaluate the interaction between physical activity
      levels and the expression of genes that modulate the susceptibility to many
      chronic diseases. Benefits of exercise extend beyond fitness to better health.
      Molecular biology is an important tool which should lead to improved physical
      performance and health in both elite athletes and the general public.

PMID- 9578382
TI  - Muscle pH regulation: role of training.
AB  - In most cell types, including resting skeletal muscle fibers, internal pH (pHi)
      is kept constant at a relatively alkaline level. The high pHi is obtained in
      spite of a chronic acid load resulting from cellular metabolism and passive
      influx of protons driven by electrochemical forces. Regulation of pHi depends on
      continuous activity of membrane transport systems that mediate an outflux of H+
      (or bicarbonate influx), whereby the acid load is counterbalanced. The
      transporters involved in muscle pH regulation at rest are the Na+/H+ exchange
      system as well as the Na+-dependent and Na+-independent Cl- bicarbonate transport
      systems. The Na+/H+ exchanger seems to be active at resting pHi levels in
      skeletal muscle. Therefore, pH homeostasis in skeletal muscle most likely
      involves an equilibrium between counter-directed H+ fluxes. A minor fraction of
      H+ release during intense exercise is mediated by the Na+/H+ exchanger. The
      capacity of this system is increased with training and hypoxia in rat skeletal
      muscle. The dominant acid extruding system associated with intense exercise is
      the lactate/H+ co-transporter. It has been demonstrated that the capacity of the
      lactate/H+ co-transporter of rat skeletal muscle is upregulated with training and
      chronic electrical stimulation, and that it is reduced upon denervation and
      hindlimb unweighting. Moreover, athletes can have an elevated lactate/H+ co
      transport capacity, whereas the thigh muscle of spinal cord-injured individuals
      has a lower transport capacity than the one of healthy untrained subjects. Thus,
      it appears that the capacity of the lactate/H+ transporter is affected by the
      level of muscle activity in both rats and humans. In addition, the rate of H+
      release from muscle may also be influenced by capillarization and local blood
      flow. Finally the resulting pH displacement during acid accumulation is
      determined by the cellular buffer capacity, which may also undergo adaptive
      changes.

PMID- 9578383
TI  - Training effects on the contractile apparatus.
AB  - Skeletal muscle is an extremely heterogeneous tissue, composed of a large variety
      of fibre types. Its dynamical nature is reflected by the ability to adapt to
      altered functional demands by qualitative alterations in fibre type composition.
      The molecular basis of this versatility is that specific myofibrillar and Ca2+
      regulatory protein isoforms are assembled to functionally specialized fibre
      types. Based on this diversity, adult muscle fibres are capable of changing their
      molecular composition by altered gene expression. Myosin heavy chain (MHC)
      isoforms and their unique expression in 'pure' fibres, as well as their
      coexpression in 'hybrid' 'fibres' represent the best markers of muscle fibre
      diversity and adaptive changes. Chronic low-frequency stimulation (CLFS) and
      endurance training represent highly suitable models for studying the effects of
      increased neuromuscular activity on myofibrillar protein isoform expression and
      fibre type composition. Generally, both models induce fast-to-slow transitions in
      myofibrillar protein isoforms and fibre types. However, the responses to
      endurance training are quantitatively less pronounced than those in muscles
      exposed to CLFS. Parallel changes in isoforms of specific myofibrillar or Ca2+
      regulatory proteins during the induced fast-to-slow transitions point to the
      existence of fibre type-specific patterns of gene expression. The fast-to-slow
      transitions do not proceed in abrupt jumps from one extreme to the other, but
      occur in a gradual and orderly sequential manner. Depending on the basal protein
      isoform profile, and hence the position within the fast-slow spectrum, the
      adaptive ranges of different fibre types vary. However, adaptive ranges not only
      depend on a particular fibre type, but also are influenced by species-specific
      properties.

PMID- 9578384
TI  - Exercise-induced changes in protein metabolism.
AB  - Exercise has a profound acute effect on protein metabolism. Whereas reports on
      whole body responses to exercise have varied results, it is generally agreed
      leucine oxidation is increased during exercise, thus indicating increased net
      protein breakdown. Following endurance exercise, whole body protein breakdown is
      generally reduced from resting levels, while following eccentric exercise, both
      whole body protein breakdown and leucine oxidation are increased. Whole body
      protein synthesis, on the other hand, is either increased or unchanged. Much of
      the disagreement in the results of studies on the response of whole body protein
      metabolism to exercise may be attributed to the limitations of the available
      methods. Even if the methodology accurately reflects whole body metabolism, this
      may not reflect changes in the protein metabolism of muscle. Although endurance
      exercise has not been studied, muscle protein breakdown is increased following
      resistance exercise. There is a concomitant, and qualitatively greater, increase
      in muscle protein synthesis following resistance exercise, which may last for as
      long as 48 h. Increased muscle protein synthesis is linked to increased
      intramuscular availability of amino acids, and thus, to increased blood flow and
      increased amino acid delivery to the muscle, as well as increased amino acid
      transport. Administration of exogenous amino acids after exercise increases
      protein synthesis while ameliorating protein breakdown, thus improving net muscle
      protein balance. While it is clear that muscle protein synthesis and protein
      breakdown increase in a qualitatively similar manner following exercise, the
      mechanisms of stimulation have yet to be determined. However, we propose that the
      intracellular availability of amino acids is the link between these processes.

PMID- 9578385
TI  - Catecholamines, hypoxia and high altitude.
AB  - Hypoxia is a potent activator of the sympathetic nervous system by stimulating
      arterial chemoreceptors. However, out of 15 laboratory studies on the effects of
      acute and prolonged hypoxia on catecholamines, 14 failed to show any changes in
      plasma or urinary noradrenaline and only four studies showed significant
      increases in plasma or urinary adrenaline. By contrast, six out of eight studies
      on MSNA showed increased sympathetic nerve activity to the leg. An increased
      clearance of plasma catecholamines during hypoxia may be a possible explanation.
      Furthermore, many of the studies had limitations in a number of subjects and
      catecholamine assays used. Emotional aspects of the study protocols, which could
      contribute to the increase in adrenaline, was only assessed by sham runs in one
      chamber study. However, 13 out of 14 reviewed field studies on subjects staying
      for more than 1 week at high altitude, reported increased plasma or urinary
      excretion of noradrenaline which may be compatible with increased sympathetic
      activity. Adrenaline changed to a lesser degree. Out of seven studies on more
      short-term (4 h to 3 days) exposure to high altitude, only one demonstrated
      significantly increased plasma noradrenaline. In this study, however, several
      subjects had been exposed to high altitude less than 1 week before the
      experiment. In a new study on 12 climbers reported in this paper, a temporary
      reduction in plasma catecholamines was found 2 days after arrival at 4200 m.
      There was a steady increase towards normal levels after 1 week. Plasma
      vasopressin (AVP) increased suggesting a compensatory mechanism. Both plasma
      noradrenaline and adrenaline were positively correlated with oxygen saturation in
      these subjects. Thus, in previously unacclimatized subjects, short-term exposure
      to high altitude does not increase plasma catecholamines, rather plasma levels
      decreased. In addition to increased clearance, there is some evidence of reduced
      synthesis of catecholamines during short-term hypoxia. The oxygen sensitivity of
      tyrosine hydroxylase (TH) activity, may be one possible mechanism.

PMID- 9578386
TI  - Role of nitric oxide in skeletal muscle: synthesis, distribution and functional
      importance.
AB  - Over the last two decades, nitric oxide (NO) has been established as a novel
      mediator of biological processes, ranging from vascular control to long-term
      memory, from tissue inflammation to penile erection. This paper reviews recent
      research which shows that NO and its derivatives also are synthesized within
      skeletal muscle and that NO derivatives influence various aspects of muscle
      function. Individual muscle fibres express one or both of the constitutive NO
      synthase (NOS) isoforms. Type I (neuronal) NOS is localized to the sarcolemma of
      fast fibres; type III (endothelial) NOS is associated with mitochondria. Isolated
      skeletal muscle produces NO at low rates under resting conditions and at higher
      rates during repetitive contraction. NO appears to mediate cell-cell interactions
      in muscle, including vasodilation and inhibition of leucocyte adhesion. NO also
      acts directly on muscle fibres to alter cell function. Muscle metabolism appears
      to be NO-sensitive at several sites, including glucose uptake, glycolysis,
      mitochondrial oxygen consumption and creatine kinase activity. NO also modulates
      muscle contraction, inhibiting force output by altering excitation-contraction
      coupling. The mechanisms of NO action are likely to include direct effects on
      redox-sensitive regulatory proteins, interaction with endogenous reactive oxygen
      species, and activation of second messengers such as cyclic guanosine
      monophosphate (cGMP). In conclusion, research published over the past few years
      makes it clear that skeletal muscle produces NO and that endogenous NO modulates
      muscle function. Much remains to be learned, however, about the physiological
      importance of NO actions and about their underlying mechanisms.

PMID- 9578387
TI  - Regulation of skeletal muscle perfusion during exercise.
AB  - For exercise to be sustained, it is essential that adequate blood flow be
      provided to skeletal muscle. The local vascular control mechanisms involved in
      regulating muscle perfusion during exercise include metabolic control,
      endothelium-mediated control, propagated responses, myogenic control, and the
      muscle pump. The primary determinant of muscle perfusion during sustained
      exercise is the metabolic rate of the muscle. Metabolites from contracting muscle
      diffuse to resistance arterioles and act directly to induce vasodilation, or
      indirectly to inhibit noradrenaline release from sympathetic nerve endings and
      oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium
      also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that
      are prominent in establishing basal vascular tone, but these substances do not
      appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth
      muscle cells may also be involved in propagating vasodilator signals along
      arterioles to parent and daughter vessels. Myogenic autoregulation does not
      appear to be involved in the exercise hyperemia in muscle, but the rhythmic
      propulsion of blood from skeletal muscle veins facilitates venous return to the
      heart and muscle perfusion. It appears that the primary determinants of sustained
      exercise hyperemia in skeletal muscle are metabolic vasodilation and increased
      vascular conductance via the muscle pump. Additionally, sympathetic neural
      control is important in regulating muscle blood flow during exercise.

PMID- 9578388
TI  - Skeletal muscle blood flow in humans and its regulation during exercise.
AB  - Regional limb blood flow has been measured with dilution techniques (cardio-green
      or thermodilution) and ultrasound Doppler. When applied to the femoral artery and
      vein at rest and during dynamical exercise these methods give similar
      reproducible results. The blood flow in the femoral artery is approximately 0.3 L
      min(-1) at rest and increases linearly with dynamical knee-extensor exercise as a
      function of the power output to 6-10 L min[-1] (Q= 1.94 + 0.07 load). Considering
      the size of the knee-extensor muscles, perfusion during peak effort may amount to
      2-3 L kg(-1) min(-1), i.e. approximately 100-fold elevation from rest. The onset
      of hyperaemia is very fast at the start of exercise with T 1/2 of 2-10 s related
      to the power output with the muscle pump bringing about the very first increase
      in blood flow. A steady level is reached within approximately 10-150 s of
      exercise. At all exercise intensities the blood flow fluctuates primarily due to
      the variation in intramuscular pressure, resulting in a phase shift with the
      pulse pressure as a superimposed minor influence. Among the many vasoactive
      compounds likely to contribute to the vasodilation after the first contraction
      adenosine is a primary candidate as it can be demonstrated to (1) cause a change
      in limb blood flow when infused i.a., that is similar in time and magnitude as
      observed in exercise, and (2) become elevated in the interstitial space
      (microdialysis technique) during exercise to levels inducing vasodilation. NO
      appears less likely since NOS blockade with L-NMMA causing a reduced blood flow
      at rest and during recovery, it has no effect during exercise. Muscle contraction
      causes with some delay (60 s) an elevation in muscle sympathetic nerve activity
      (MSNA), related to the exercise intensity. The compounds produced in the
      contracting muscle activating the group IIl-IV sensory nerves (the muscle reflex)
      are unknown. In small muscle group exercise an elevation in MSNA may not cause
      vasoconstriction (functional sympatholysis). The mechanism for functional
      sympatholysis is still unknown. However, when engaging a large fraction of the
      muscle mass more intensely during exercise, the MSNA has an important functional
      role in maintaining blood pressure by limiting blood flow also to exercising
      muscles.

PMID- 9578389
TI  - Axonal sprouts containing calcitonin gene-related peptide and substance P form
      pericellular baskets around large diameter neurons after sciatic nerve
      transection in the rat.
AB  - Trauma to a peripheral nerve is followed by anatomical remodelling proximal to
      the lesion, including sprouting of perivascular axons to form baskets of
      noradrenergic terminals ("rings") around large diameter primary afferent somata
      in the dorsal root ganglia containing lesioned neurons and sprouting of Abeta
      axons terminating deep in the dorsal horn into Lamina II. These abnormal
      structural associations may contribute to the changes in sensory processing that
      lead to neuropathic pain. The trigger for sprouting of sympathetic axons is
      probably a neurotrophin (such as nerve growth factor) concentrated locally. Nerve
      growth factor messenger RNA is known to be increased in dorsal root ganglia after
      sciatic nerve transection and increased local nerve growth factor elicits
      collateral sprouting of intact sympathetic terminals into adjacent denervated
      skin. Nociceptive terminals containing calcitonin gene-related peptide, with or
      without substance P, also sprout in response to raised concentrations of nerve
      growth factor. We have found that axons of small sensory neurons immunoreactive
      for these peptides also form rings around large diameter dorsal root ganglion
      cells of adult rats after sciatic nerve transection, concurrently with the
      development of rings of noradrenergic terminals.

PMID- 9578391
TI  - Cell-specific dendritic localization of glycine receptor alpha subunit messenger
      RNAs.
AB  - The regional and subcellular localizations of glycine receptor complex messenger
      RNAs were determined in the adult rat central nervous system using non
      radioactive in situ hybridization. The present investigation focused on glycine
      receptors alpha1 and alpha2 subunit messenger RNAs. Within the central nervous
      system we observed that the glycine receptor alpha1 and alpha2 subunit messenger
      RNAs are widely expressed. At the subcellular level, these messenger RNAs are
      present either in neuronal somata and dendrites or somata only. Furthermore,
      among different regions as well as within the same region the subcellular
      localizations of both alpha subunit messenger RNAs are cell type-dependent. In
      contrast, the regional distributions of beta subunit and gephyrin messenger RNAs
      are essentially as previously described [Fujita M. (1991) Brain Res. 560, 23-37;
      Malosio M.-L. et al. (1991) Eur. molec. Biol. Org. J. 9, 2401-2409; Kirsch J. et
      al. (1993) Eur. J. Neurosci. 5, 1109-1117] and their messenger RNAs are confined
      predominantly within the somata of neurons [Kirsch J. et al. (1993); Racca et al.
      (1997) J. Neurosci. 17, 1691-1700]. These results demonstrate that the glycine
      receptor complex messenger RNAs are broadly expressed in the central nervous
      system and that the glycine receptor alpha1 and alpha2 subunit messenger RNAs
      differ in their subcellular localization depending on the neuronal population.
      The latter finding suggests that different mechanisms for the localization of
      glycine receptor alpha1 and alpha2 subunit messenger RNAs are used by distinct
      populations of neurons.

PMID- 9578390
TI  - The neuronal organization of the supracapsular part of the stria terminalis in
      the rat: the dorsal component of the extended amygdala.
AB  - In the present normal anatomical light and electron microscopic study in the rat,
      histochemical (Nissl, Timm, Golgi) or immunocytochemical (microtubule-associated
      protein type 2, glutamate decarboxylase, glutamate receptor subunit 1,
      synaptophysin) stains were used to analyse neurons embedded within the stria
      terminalis and their associated neuropil. These cells are closely related to the
      bed nucleus of the stria terminalis and the centromedial amygdala, and have been
      termed the "supracapsular part of the bed nucleus of the stria terminalis". The
      largest part of this neuronal complex is located in the ventrolateral part of the
      stria, where it appears as a round or oval "lateral pocket" in virtually any type
      of light microscopic preparation because of its collection of neuronal cell
      bodies and dense neuropil, in addition to a lacework of unmyelinated axons. A
      much smaller but still distinct "medial pocket" is located in the medial corner
      of the stria. The large lateral subdivision of the supracapsular stria terminalis
      is directly continuous with the lateral bed nucleus of the stria terminalis and
      extends to the central amygdaloid nucleus, containing a column of neurons that is
      only broken up into cell clusters at the most caudal levels of the stria as it
      drops vertically toward the amygdala. The considerably smaller medial subdivision
      appears, in turn, to be directly continuous with the medial part of the bed
      nucleus of the stria terminalis. The medial column tapers off more rapidly than
      the lateral part, so that as the middle levels are approached, only small
      interrupted clusters of cells are seen. Solitary neurons can also be found in
      practically every part of the stria terminalis except among the ventrally located
      axons of the commissural component. Most of the neurons are small to medium in
      size, as viewed in transverse sections of the stria, but larger neurons are also
      encountered. In sections parallel to the stria, many neurons are fusiform in
      appearance. The dendrites are often aligned in a longitudinal fashion; many of
      the dendrites related to the cells in the lateral pocket are moderately to
      densely spined, whereas those in the medial pocket are more sparsely spined. The
      neuropil in both the lateral and medial pockets is characterized by boutons,
      bundles of unmyelinated axons, and dendrites. Based on their vesicle content, the
      boutons are divided into three major types: (A) round or slightly oval, agranular
      vesicles of uniform size; (B) pleomorphic, agranular vesicles, many of which are
      flattened; and (C) pleomorphic agranular vesicles, some of which are considerably
      larger than the ones in type B boutons. Type A boutons establish contacts with
      both dendritic spines and shafts, whereas types B and C usually contact dendritic
      shafts and sometimes somata. These synaptic components are similar to those
      described earlier for the central and medial amygdaloid nuclei. Overall, our
      results support the contention advanced in 1923 by Johnston [J. comp. Neurol. 35,
      337481] that the cells accompanying the stria terminalis are interconnecting
      columns of a macrostructure encompassing the bed nucleus of the stria terminalis
      and centromedial amygdala. More recently, it has been appreciated that columns of
      neurons below the globus pallidus also belong to this macrostructure [Alheid G.
      F. et al. (1995) In The Rat Nervous System, 2nd edn, pp. 495 578, Academic, San
      Diego; de Olmos J. S. et al. (1985) In The Rat Nervous System, pp. 223-334,
      Academic, Sydney], which has been named the "extended amygdala".

PMID- 9578392
TI  - Region-specific migration of embryonic glia grafted to the neonatal brain.
AB  - Cell fate determination and region-specific migration among neurons from the
      developing brain have been widely studied. Because similar attributes have been
      mostly unexplored in reference to glia, the present study has characterized the
      migratory responses of glia from diverse regions of the embryonic mouse brain
      after their transplantation to the brains of early postnatal (still developing)
      rats. Through the use of the mouse-specific, glial-specific marker M2,
      immunocytochemical processing of host tissues three to four weeks after
      transplantation revealed notable difference in the migratory patterns of
      phylogenetically diverse populations of glia. While glia from the ventral
      mesencephalon, cerebral cortex, and cerebellar neuroepithelium all showed a
      similar affinity for the nigropallidal tract after grafting to the internal
      capsule, only ventral mesencephalon-derived glia showed restricted migration
      toward and into the substantia nigra after transplantation to the thalamus or
      pontine tegmentum. These results suggest the presence of a highly favourable
      substrate for glial migration along developing fibre tracts, but, more
      importantly, indicates the potential for certain glia to respond to particular
      (region-specific) distal cues within the developing brain.

PMID- 9578393
TI  - Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal
      responses to a novel stressor after chronic stress.
AB  - Animals exposed to chronic stress exhibit normal or enhanced hypothalamic
      pituitary adrenal responses to novel, acute stimuli despite the inhibitory
      endogenous corticosteroid response to the chronic stressor. Prior stress is
      thought to induce a central facilitatory trace that, upon exposure to a novel
      stimulus, balances or overcomes the inhibitory effects of corticosterone. The
      neuroanatomical basis for this facilitation of hypothalamic pituitary adrenal
      responses is unknown. In this study, we first show increased adrenocorticotropin
      and corticosterone responses to the novel stressor of restraint in rats exposed
      to intermittent cold for seven days. We then compared numbers of Fos
      immunoreactive cells in 26 sites in control and chronically stressed rats at
      various times after onset of a 30 min restraint. At 60 min, density of Fos
      stained cells was significantly higher in chronically stressed than in control
      rats in the parabrachial/Kolliker-Fuse area, posterior paraventricular thalamus,
      central, basolateral and basomedial nuclei of the amygdala and parvocellular
      paraventricular hypothalamus. The posterior paraventricular nucleus of the
      thalamus receives projections from the parabrachial nucleus and projects heavily
      to the differentially stained subnuclei of the amygdala, which in turn project to
      the parvocellular paraventricular nucleus of the hypothalamus. We propose that
      increased activity in the parabrachial-posterior paraventricular thalamus
      amygdala-parvocellular paraventricular hypothalamus underlies facilitation of the
      hypothalamic pituitary-adrenal axis to novel stress in chronically stressed rats.
      We confirmed part of this proposal by showing that lesions of the posterior
      paraventricular nucleus of the thalamus increase adrenocorticotropin responses to
      restraint only in previously chronically stressed animals. This potential circuit
      provides a basis for further examination of the functional roles of these regions
      in stress-induced facilitation of hypothalamic pituitary-adrenal activity.

PMID- 9578394
TI  - Spatiotemporal response properties of cerebellar Purkinje cells to neck
      displacement.
AB  - The activity of 184 Purkinje cells and 58 unidentified neurons located within the
      cerebellar anterior vermis was recorded in decerebrate cats during wobble of the
      body under a fixed head. This stimulus induced a neck displacement of constant
      amplitude (2.5 degrees) whose direction rotated at the constant velocity of 56.2
      degrees/s on the horizontal plane, both in the clockwise and counterclockwise
      directions. It was then possible to evaluate the spatiotemporal characteristics
      of unit responses to neck displacement in the vertical planes; 131 of 184
      Purkinje cells (71%) and 35 of 58 unidentified cells (60%) responded to clockwise
      and/or counterclockwise rotations. In particular, among the responsive units, 44%
      of the Purkinje cells and 37% of the unidentified cells showed an equal amplitude
      modulation during clockwise and counterclockwise rotations. These units are
      expected to show a maximal response sensitivity for neck displacement in a
      preferred direction, a null response for perpendicularly oriented stimuli and a
      constant temporal phase (narrowly tuned neurons). In 28% of the Purkinje cells
      and 40% of the unidentified cells, responses of different amplitudes were
      observed during clockwise and counterclockwise rotations. These neurons should
      display a preferred direction of response to neck displacement, lack of null
      response directions and a temporal phase changing with the stimulus direction
      (broadly tuned neurons). Finally, 27% of the Purkinje cells and 23% of the
      unidentified cells responded only to wobble in the clockwise or counterclockwise
      direction (unidirectional units). This behavior predicts equal sensitivities for
      all the directions of neck displacement and a response phase changing linearly
      with the direction of neck displacement. A maximal sensitivity vector (Smax),
      aligned with the preferred direction of the neuron, was evaluated for the
      bidirectional narrowly tuned and broadly tuned units. Its amplitude and temporal
      phase corresponded to the response characteristics expected for stimuli in the
      preferred direction of the cell. Smax directions were distributed over the
      horizontal plane. Most of them, however, were closer to the pitch than to the
      roll axis and pointed towards the animal's tail. Among pitch-related Purkinje
      cells, the temporal phase of Smax was small with a predominance of phase lags;
      phase leads of rather large amplitude were usually observed for roll-related
      Purkinje cells. The possibility that the recorded population of units coded the
      direction of neck displacement was tested by assuming that each cell gave a
      vectorial contribution related to its response properties and that the vectorial
      sum of such contributions represented the outcome of the population code. Dynamic
      body-to-head displacements in four different directions were simulated and for
      each direction 12 population vectors were evaluated at regular intervals of the
      stimulus cycle. The direction of the population vector was related to that of the
      stimulus, but the correspondence was close only for the pitch direction.
      Moreover, the amplitude of the population vector depended upon the direction of
      the stimulus, being larger for pitch than for roll displacements. Due to the
      efferent connections of the explored cerebellar region, the neuronal signals
      generated by the Purkinje cell population are probably transferred to the spinal
      cord, where they may differentially affect the amplitude and the spatial
      properties of the neck reflexes according to the direction of neck displacement.

PMID- 9578395
TI  - A role for serotonin in the circadian system revealed by the distribution of
      serotonin transporter and light-induced Fos immunoreactivity in the
      suprachiasmatic nucleus and intergeniculate leaflet.
AB  - Components of the circadian system, the suprachiasmatic nucleus and the
      intergeniculate leaflet receive serotonin input from the raphe nuclei.
      Manipulations of serotonin neurotransmission disrupt cellular,
      electrophysiological, and behavioural responses of the circadian system to light,
      suggesting that serotonin plays a modulatory role in photic regulation of
      circadian rhythms. To study the relation between serotonin afferents and light
      activated cells in the suprachiasmatic nucleus and intergeniculate leaflet, we
      used immunostaining for the serotonin transporter and for the transcription
      factor, Fos. Serotonin transporter, a plasma membrane protein located on
      serotonin neurons, regulates the amount of serotonin available for
      neurotransmission by re-accumulating released serotonin into presynaptic neurons;
      expression of Fos in the suprachiasmatic nucleus identifies light-activated cells
      involved in photic resetting of circadian clock phase. In the suprachiasmatic
      nucleus, immunostaining for serotonin transporter revealed a dense plexus of
      fibres concentrated primarily in the ventrolateral region. In the intergeniculate
      leaflet, serotonin transporter immunostaining identified vertically-oriented
      columns of fibres. Serotonin transporter immunostaining was abolished by
      pretreatment with the serotonin neurotoxin, 5,7-dihydroxytryptamine. Exposure to
      light for 30 min during the dark phase of the light cycle induced Fos expression
      in the ventrolateral suprachiasmatic nucleus and intergeniculate leaflet regions.
      In both structures the Fos-expressing cells were encircled by serotonin
      transporter-immunoreactive fibres often in close apposition to these cells. These
      results support the idea that serotonin activity plays a modulatory role in
      processing of photic information within the circadian system.

PMID- 9578396
TI  - Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid
      agonist-stimulated [35S]guanylyl-5'O-(thio)-triphosphate binding in the basal
      ganglia of aged rats.
AB  - Recent reports have demonstrated that cannabinoid receptor binding decreases in
      several neurodegenerative diseases related to extrapyramidal function. However,
      there is little evidence with regard to potential changes of these receptors
      during senescence. The present study was designed to determine the possible
      existence of ageing-induced changes in cannabinoid receptor binding and gene
      expression in extrapyramidal areas. To this end, we analysed cannabinoid receptor
      binding and basal and cannabinoid receptor agonist-stimulated [35S]guanylyl-5'-O
      (gamma-thio)-triphosphate binding, by using autoradiography, and cannabinoid
      receptor messenger RNA levels, by using in situ hybridization, in slide-mounted
      brain sections obtained from young (three-month-old) and aged (>two-year-old)
      rats. Results were as follows. Aged rats exhibited a marked decrease in
      cannabinoid receptor binding in most of the basal ganglia, excepting the globus
      pallidus which had similar binding levels in both young and aged rats. The
      highest decreases were in the entopeduncular nucleus (-49.6%) and substantia
      nigra pars reticulata (-45.2%), whereas more moderate decreases were found in the
      lateral caudate putamen (-29%) and only a decremental trend in the medial caudate
      putamen (-13.1%). These decreases in cannabinoid receptor binding were paralleled
      by less marked increases in WIN 55212-2-stimulated [35S]guanylyl-5'-O-(gamma
      thio)-triphosphate binding in these structures in aged rats (% of agonist
      stimulation: 189% in the substantia nigra; 29.4% in the lateral caudate putamen)
      as compared to young rats (296% and 53.2%, respectively). Contrarily, the
      percentage of agonist stimulation was similar in the globus pallidus, an area
      where cannabinoid receptor binding did not change during ageing, of aged (205.5%)
      and young (215.5%) rats. In addition, aged rats also exhibited significant
      reductions in the cannabinoid receptor messenger RNA levels in the medial (
      14.3%) and, in particular, in the lateral (-29.4%) caudate putamen, the area
      where the cell bodies of cannabinoid receptor-containing neurons, projecting to
      the substantia nigra, entopeduncular nucleus and globus pallidus, are located. In
      summary, the synthesis and binding levels of cannabinoid receptors markedly
      dropped in different structures of the extrapyramidal system of aged rats. Since
      these receptors, located in the basal ganglia, seem to play a role in motor
      control, this loss of cannabinoid receptors might be related to the motor
      impairment which progressively appears during senescence.

PMID- 9578397
TI  - Localization of alpha2C-adrenergic receptor immunoreactivity in catecholaminergic
      neurons in the rat central nervous system.
AB  - Given the importance of alpha2-adrenergic receptors in the regulation of
      catecholaminergic transmission, we analysed the distribution of immunoreactivity
      corresponding to the C-subtype of alpha2-adrenergic receptor in central
      catecholaminergic neurons using double-label immunohistochemistry with antibodies
      directed against alpha2C-adrenergic receptors and tyrosine hydroxylase. Cells
      exhibiting both alpha2C-adrenergic receptor and tyrosine hydroxylase
      immunoreactivity were found in most areas containing catecholaminergic cell
      groups. However, the percentage of double-labelled cells varied in a region
      specific manner. In the medulla, alpha2C-adrenergic receptor immunoreactivity was
      characteristic of only a minority of cells exhibiting tyrosine hydroxylase
      immunoreactivity (40-43% in area A1/C1, 27-36% in area A2/C2, 35% in area C3)
      while a larger percentage of double-labelled cells was observed in the pons (65%
      in A5, 92% in locus coeruleus, 68% in A7). In the midbrain, alpha2C-adrenergic
      receptor immunoreactivity was detected in most tyrosine hydroxylase
      immunoreactive cells in dopaminergic regions (63% in the retrorubral field, 77
      83% in substantia nigra, 67% in ventral tegmental area). These results suggest
      that alpha2C-adrenergic receptors may act as autoreceptors on some central
      adrenergic and noradrenergic neurons. In addition, the colocalization of alpha2C
      adrenergic receptor and tyrosine hydroxylase immunoreactivity in dopaminergic
      cell groups suggests that reported effects of alpha2-adrenergic receptor agonists
      in these areas may be mediated by the C-subtype.

PMID- 9578398
TI  - Cell cycle-related gene expression in the adult rat brain: selective induction of
      cyclin G1 and p21WAF1/CIP1 in neurons following focal cerebral ischemia.
AB  - The present studies were initiated to investigate whether p53 transactivated
      target genes are induced in a rat model of focal cerebral ischemia. Therefore, we
      applied in situ hybridization, immunocytochemistry and western blotting to study
      the temporal and spatial expression of p53 and its transcriptional targets Bax,
      p21 and cyclin G1 following permanent middle cerebral artery occlusion in the
      rat. Cyclin G1 immunoreactivity was constitutively expressed in the nuclei of
      cells in the choroid plexus and ependymal cell layer and in the cytoplasm of cell
      bodies and dendrites of pyramidal neurons of the cerebral cortex. Cyclin G1
      messenger RNA and protein levels transiently increased to 150% of contralateral
      levels in neurons of the ipsilateral frontal and parietal cortex and striatum 3 h
      following middle cerebral artery occlusion. A low level of constitutively
      expressed p21 messenger RNA and protein was found in nuclei of cells in the
      choroid plexus, oligodendrocytes and neurons. p21 messenger RNA and protein
      levels gradually increased to 250% and 140% of contralateral levels in areas
      bordering the infarct core up to 6 h following middle cerebral artery occlusion.
      In contrast, p53 and Bax messenger RNA and protein levels, and protein levels of
      p27, cyclin-dependent kinase 5, p35 and cyclin E decreased in the infarct core
      and border areas with time after middle cerebral artery occlusion. The selective
      up-regulation of cyclin G1 and p21 in neurons in the border zone of a focal
      ischemic infarct indicates their involvement in an adaptive response to ischemic
      injury. The possible participation of cyclin G1 and p21 in a signal transduction
      pathway associated with ischemia-induced cellular stress is discussed.

PMID- 9578399
TI  - Focal cerebral ischemia in rats induces expression of P75 neurotrophin receptor
      in resistant striatal cholinergic neurons.
AB  - Expression of p75 neurotrophin receptor and survival of medium-sized spiny
      projection neurons and cholinergic interneurons in the rat striatum were studied
      using immunocytochemistry at different times after transient, unilateral middle
      cerebral artery occlusion. Thirty minutes of middle cerebral artery occlusion
      caused a major loss of projection neurons, identified by their immunoreactivity
      to dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a
      molecular weight of 32,000, in the lateral part of the striatum, as observed at
      48 h following the insult with no further change at one week. In contrast, no
      reduction of the number of choline acetyltransferase-positive, cholinergic
      interneurons, which also expressed TrkA, was detected at either time-point. At 48
      h following middle cerebral artery occlusion, expression of p75 neurotrophin
      receptor was observed in striatal cells which, by the use of double-label
      immunostaining, were identified as the cholinergic interneurons. No p75
      neurotrophin receptor immunoreactivity remained in cholinergic cells after one
      week of reperfusion. Based on current hypotheses regarding the function of the
      p75 neurotrophin receptor, the transient expression of this receptor in striatal
      cholinergic interneurons might contribute to their high resistance to ischemic
      neuronal death. However, the expression of p75 neurotrophin receptor could also
      be a first step in a pathway leading to apoptosis, which is inhibited after the
      present insult due to concomitant activation of TrkA.

PMID- 9578400
TI  - Effect of propentofylline on free radical generation during cerebral hypoxia in
      the newborn piglet.
AB  - The present study tests the hypothesis that propentofylline, an adenosine re
      uptake inhibitor, will reduce free radical generation during cerebral hypoxia.
      Ten newborn piglets were pretreated with propentofylline (10 mg/kg), five of
      which were subjected to hypoxia, while the other five were maintained at
      normoxia. Five untreated control piglets underwent the same conditions. Hypoxia
      was induced through a decrease in FiO2 to 0.11 and documented biochemically by a
      decrease in ATP and phosphocreatine levels. Free radical formation in the cortex
      was detected directly using electron spin resonance spectroscopy with a spin trap
      technique. Results demonstrate that free radicals, corresponding to the alkoxyl
      radical, increased significantly following hypoxia, and that this increase was
      inhibited by pretreatment with propentofylline. Conjugated dienes, a lipid
      peroxidation product, also increased following hypoxia and were subsequently
      inhibited by propentofylline. The administration of propentofylline also
      significantly limited the hypoxia-induced decrease in tissue levels of ATP and
      phosphocreatine. These data demonstrate that pretreatment with propentofylline
      decreased free radical generation and lipid peroxidation as well as preserved
      high energy phosphates during cerebral hypoxia.

PMID- 9578401
TI  - Spatiotemporal patterns of expression of extracellular matrix molecules in the
      developing and adult rat olfactory system.
AB  - Using immunocytochemical methods, we have examined extensively the spatial and
      temporal patterns of expression of three extracellular matrix molecules-laminin,
      fibronectin, and type IV collagen-in the embryonic, postnatal (days 2 and 11) and
      adult rat olfactory system. The study started at embryonic day 14 when olfactory
      fibres and their associated migrating cells course through the nasal mesenchyme.
      From embryonic day 14 to the adult, a sheet-like pattern of labelling for
      laminin, fibronectin and type IV collagen was observed along the basal surface of
      the olfactory epithelium and around the telencephalon. This type of labelling was
      continuous around the telencephalic vesicle, whereas it appeared disrupted in the
      basal lamina of the olfactory epithelium to permit exit of the olfactory axons
      and their associated migrating cells into the mesenchyme. From embryonic day 14
      to day 20, punctate labelling for the three molecules studied was observed along
      the mesenchymal olfactory pathway, the ventral part of the olfactory bulb, the
      olfactory nerve layer and the presumptive glomerular layer, respectively. By
      embryonic day 17, the punctate labelling initially detected in the mesenchymal
      olfactory pathway was replaced by a sheet-like pattern related to the mature
      basal lamina surrounding the olfactory axon fascicles. Punctate labelling for
      laminin and type IV collagen persisted in the olfactory nerve layer and around
      the glomeruli through adult life whereas that of fibronectin declined and
      disappeared by postnatal day 2. The spatiotemporal distribution of the punctate
      pattern for laminin, fibronectin and type IV collagen observed in the embryonic
      olfactory system suggests a role in delineating the pathway for olfactory axon
      elongation. The continuous expression of laminin and type IV collagen in the
      adult olfactory bulb may be related to the regenerative activity and high
      plasticity of the olfactory system.

PMID- 9578402
TI  - Exposure to prenatal nicotine transiently increases neuronal nicotinic receptor
      subunit alpha7, alpha4 and beta2 messenger RNAs in the postnatal rat brain.
AB  - This study determined the effects of prenatal nicotine exposure (2 mg/kg/day) in
      Sprague Dawley CD rats via subcutaneously implanted osmotic minipumps, during
      gestational days 7-21, on postnatal levels of neuronal nicotinic receptor alpha4,
      alpha7 and beta2 subunit messenger RNAs. Northern analysis of postnatal day 1, 7,
      14 and 28 hippocampal/septal and cortical total RNA using alpha-[32P]dCTP-labeled
      alpha4, alpha7 and beta2 complementary DNA probes identified a single (5.7-kb)
      alpha7 messenger RNA, three (2.4-, 3.8- and 8.0-kb) alpha4 messenger RNAs and
      four (3.7-, 5.0-, 7.5- and 10.0-kb) beta2 messenger RNAs. In comparison to
      prenatal saline, prenatal nicotine produced several significantly higher
      messenger RNA levels (cortical: 5.7-kb alpha7, 2.4-, 3.8- and 8.0-kb alpha4, 10.0
      kb beta2; hippocampal/septal: 2.4- and 8.0-kb alpha4); these increases occurred
      predominantly on, but were not restricted to, postnatal day 14. Effects of
      nicotine were generally resolved by postnatal day 28. Collapsing the data across
      sex and age, a significant treatment effect indicated that hippocampal/septal and
      cortical 8.0-kb alpha4 messenger RNA levels and 10.0-kb beta2 messenger RNA
      levels were significantly higher following prenatal nicotine exposure. This is
      the first study indicating that prenatal nicotine produces alterations in
      developing postnatal rat neuronal nicotinic receptor messenger RNA levels,
      possibly by premature stimulation of neuronal nicotinic receptors. These results
      further implicate the teratogenic potential of nicotine in postnatal neuronal
      development.

PMID- 9578403
TI  - Postnatal development of excitatory synaptic input to the rat neostriatum: an
      electron microscopic study.
AB  - The distribution and density of asymmetric synapses including biocytin-labelled
      corticostriatal synapses of the rat neostriatum were examined at postnatal day 10
      (P10), P15, P21 and in adults. The density of asymmetric synapses in the adult
      neostriatum (28.0 synapses/100 microm2) was significantly greater than that in
      neonates at P15 (14.4 synapses/100 microm2) and P10 (11.5 synapses/100 microm2),
      but not at P21 (24.2+/-1.5 synapses/100 microm2). The increased density of
      asymmetric synapses in the adult neostriatum was due primarily to an increase in
      the number of axospinous synapses. The density of axospinous synapses was
      greatest in adults (22.3 synapses/100 microm2) and significantly less at P21
      (15.3 synapses/100 microm2), P15 (5.9 synapses/100 microm2), and P10 (2.0
      synapses/100 microm2). The density of axodendritic synapses, however, remained
      similar at all ages (adult, 3.9+/-1.1 synapses/100 microm2; P21, 6.0+/-1.2
      synapses/100 microm2; P15, 5.7+/-0.8 synapses/100 microm2 or P10, 7.2+/-1.3
      synapses/100 microm2). Iontophoretic injection of biocytin into the lateral
      frontal agranular cortex produced labelling of corticostriatal afferents which
      formed asymmetric synapses in the neostriatum. The distribution of termination
      sites of biocytin-labelled corticostriatal boutons showed a pattern of
      development similar to the unlabelled asymmetric synapses. The present study
      shows that the increase in the overall number of asymmetric synapses over the
      first three postnatal weeks can be attributed to an increase in the density of
      asymmetric axospinous synapses. During the same period little change is noted in
      the number or density of asymmetric axodendritic synapses. These changes in
      excitatory synaptic input to medium spiny neurons may explain some of the
      previously described electrophysiological differences noted between the neonatal
      and adult neostriatum.

PMID- 9578404
TI  - The neurotoxin 1-methyl-4-phenylpyridinium is sequestered within neurons that
      contain the vesicular monoamine transporter.
AB  - The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces a
      parkinsonian syndrome in man and experimental animals. The toxic metabolite of 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, exhibits
      high-affinity uptake by plasma membrane monoamine transporters and also by the
      vesicular monoamine transporter. Using autoradiographic and immunohistochemical
      methods in mice, we demonstrate the accumulation of [3H]1-methyl-4
      phenylpyridinium within neurons that contain the vesicular monoamine transporter,
      following systemic administration of [3H]1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine. Within 1-24 h following the intraperitoneal administration of
      10 microg/kg of [3H]1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, [3H]1-methyl-4
      phenylpyridine labelling was found within such regions as the locus coeruleus,
      dorsal, medial, and pallidal raphe nuclei, substantia nigra pars compacta,
      ventral tegmental area, and paraventricular nucleus of the hypothalamus. These
      regions all contain monoaminergic somata as defined by immunohistochemical
      staining with an antibody against the vesicular monoamine transporter. There was
      a positive relationship between the density of [3H]1-methyl-4-phenylpyridinium
      label and the density of vesicular monoamine transporter immunoreactivity: the
      highest densities of both were found in the locus coeruleus and lowest densities
      in the midbrain dopaminergic neurons. In addition, [3H]1-methyl-4
      phenylpyridinium labelling was detected in the bed nucleus of the stria
      terminalis and paraventricular nucleus of the thalamus, which also contained
      vesicular monoamine transporter immunoreactive nerve terminals. The present data
      indicate that low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine cause a
      significant accumulation of 1-methyl-4-phenylpyridinium within monoaminergic
      somata in parallel with the amount of vesicular monoamine transporter in the
      neuron. Since nuclei with intense labelling are not damaged by doses of 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine that are toxic to midbrain dopaminergic
      neurons, these data are consistent with the hypothesis that sequestration of 1
      methyl-4-phenylpyridinium within monoaminergic synaptic vesicles can protect the
      neurons from degeneration caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

PMID- 9578405
TI  - Distribution of Fos- and Jun-related proteins and activator protein-1 composite
      factors in mouse brain induced by neuroleptics.
AB  - The mechanisms by which the direct actions of neuroleptics are translated into
      therapeutic effects are unknown. We immunocytochemically investigated the
      expression of Fos- and Jun-related proteins and examined activator protein-1 DNA
      binding activity in ddY mouse brain 120 min after the administration of
      haloperidol (1 mg/kg), (-)-sulpiride (20 mg/kg) and a selective dopamine D1
      receptor antagonist, SCH23390 (1 mg/kg). The densities of Fos-, FosB-, Fra-1-,
      Jun- and JunD-immunoreactive nuclei induced by haloperidol and sulpiride in the
      hippocampus, piriform cortex and accumbens nucleus were higher than those in the
      control groups. The same regions showed higher densities of FosB-, Fra-1- and
      JunD-immunoreactive nuclei induced by SCH23390 compared with the control groups.
      We investigated further the activator protein-1 composite factors using super gel
      shift assays. These results suggested that induced Fos, FosB, Fra-1, Jun and JunD
      proteins constitute the activator protein-1 complex after the administration of
      haloperidol and sulpiride. In contrast, FosB, Fra-1 and JunD appear to constitute
      the activator protein-1 complex after the administration of SCH23390. Therefore,
      the diversity of activator protein-1 composite factors suggests that various
      kinds of gene are induced to act by some neuroleptics.

PMID- 9578406
TI  - Fos expression in the ferret trigeminal nuclear complex following tooth pulp
      stimulation.
AB  - The aim of this study was to establish which regions of the trigeminal nucleus
      are activated by tooth pulp stimulation in the normal ferret. The distribution of
      Fos-like immunoreactivity was examined following electrical stimulation of the
      tooth pulp in the awake and anaesthetized ferret. Stimulus-specific labelling was
      found in subnuclei caudalis and oralis of the trigeminal spinal nucleus. Three
      groups of chronically prepared animals; conscious, anaesthetized
      (alphaxolone/alphadolone) and anaesthetized-paralysed (alphaxolone/alphadolone
      with gallamine triethiodide), received electrical stimuli to both the upper and
      lower left canine teeth (1 Hz train of 3 x 0.5 ms at 200 Hz) at an amplitude of
      10 times the threshold of the jaw opening reflex. Three control groups were
      treated identically except no stimulus was given. In stimulated anaesthetized and
      anaesthetized-paralysed animals, Fos-positive profiles were seen in laminae I and
      II of subnucleus caudalis and in the medial part of subnucleus oralis. There was
      no labelling evident in subnucleus interpolaris or the main sensory nucleus, or
      contralaterally in any of the subnuclei. In all conscious stimulated animals
      there was additional bilateral Fos-positive labelling, mainly in the deeper
      laminae of subnucleus caudalis. This bilateral labelling was not stimulus
      specific as it was also seen in conscious non-stimulated animals. After
      correction for this bilateral labelling no significant difference was found
      between conscious, anaesthetized and anaesthetized-paralysed groups of stimulated
      animals or between the different groups of control animals. These results support
      the concept that the rostral parts of the trigeminal spinal nucleus are involved
      in processing of nociceptive input. They also demonstrate that light
      alphaxolone/alphadolone anaesthesia has no effect on stimulus-specific Fos
      expression following tooth pulp stimulation. The second aim of this study was to
      develop a clearly defined model for future studies in which Fos expression is no
      different to that seen in the conscious state. As in the conscious animal,
      labelling not associated with the stimulus is difficult to distinguish from
      stimulus specific labelling, further studies using this model of trigeminal
      nociceptive pathways would be best carried out in lightly anaesthetized animals.

PMID- 9578407
TI  - Regional analysis of the spatial patterns of Fos induction in brain following
      flurothyl kindling.
AB  - We have recently demonstrated that eight, daily flurothyl-induced generalized
      clonic seizures, followed by a four week stimulus-free interval, results in a
      long-lasting reduction in generalized seizure threshold and a change in the type
      of seizure expressed in response to flurothyl from clonic to tonic. There is a
      progressive increase in the probability that a mouse will express a tonic seizure
      during the four week interval, suggesting that prior flurothyl seizures initiate
      a proepileptogenic process that requires time to develop. In this study, the
      immunohistochemical detection of the c-fos protein (Fos) was used to evaluate
      whether seizure-induced epileptogenesis resulted in regional differences in the
      degree of neuronal activation. Fos immunoreactivity was examined 1.5 h following
      either a single generalized seizure, the last of eight consecutive daily seizures
      or a retest seizure evoked two weeks after the last of eight seizures. In each
      condition, generalized seizure behaviours were elicited in C57BL/6 mice using
      flurothyl and classified as either "forebrain" (face and forelimb clonus) or
      "brainstem" (running/bouncing, treading, tonic extension). The spatial
      distribution of Fos induction was compared on the basis of the seizure phenotype
      and the seizure history. The predominant differences in Fos distribution were
      found to be related to the type of seizure expressed regardless of the seizure
      history. Furthermore, the different motor components that make up a "brainstem"
      seizure could not be distinguished by the pattern of Fos labelling suggesting
      that multiple convulsive behaviours are mediated by one anatomical system.
      Finally, Fos induction in the ventromedial hypothalamic nucleus preceded and
      predicted the change in seizure type from "forebrain" to "brainstem". These data
      support the concept that separate anatomical systems mediate the expression of
      the two generalized seizure phenotypes. In addition, the ventromedial nucleus of
      the hypothalamus may be a point of interaction between the systems and may play a
      role in seizure-induced neural reorganization.

PMID- 9578408
TI  - Effects of tapering geometry and inhomogeneous ion channel distribution in a
      neuron model.
AB  - Recent experiments have produced direct evidence on the existence of various
      dendritic voltage-gated ion channels, indicating that these neuronal components
      are not just a passive medium for the propagation of synaptic excitation but a
      putative source of neuronal excitability that is reflected in the activity
      patterns occurring on the soma. In order to study possible changes in neuronal
      excitability when the distribution of dendritic voltage-activated channels is non
      uniform, and the dendritic geometry is not necessarily cylindric, we have
      developed a neuron model that incorporates two voltage-activated currents [I(Na)
      and I(K)], and in which space-dependent distributions of the system parameters
      can be treated in a mathematically simple and efficient way. Simulation results
      with the model showed that both linearly and exponentially tapering geometries
      led to marked anisotropy of the propagation of excitation, favouring the soma-to
      dendrite direction. Exponentially decaying densities of dendritic voltage
      activated channels, with appropriate choice of the parameters, induced bistable
      behaviour between the normal resting state and an intrinsic, sustained
      oscillation with cylindric as well as linear and exponential tapering dendritic
      geometry. Bistability could not be evoked when the model was reduced to a space
      independent one (point-like soma). These results suggest that both tapering
      dendritic geometry and inhomogeneous distribution of ion channels may crucially
      affect the propagation and integration of synaptic potentials, and that changes
      in dendritic channel densities might underlie pathological electrophysiological
      activities.

PMID- 9578409
TI  - Astroglial distribution of neurokinin-2 receptor immunoreactivity in the rat
      spinal cord.
AB  - Two mouse monoclonal antibodies, 11H9.1 and 1G7.10, raised against the COOH
      terminus peptide (359-390) of the rat neurokinin-2 receptor, were used to
      visualize by light and electron microscope immunocytochemistry the distribution
      of this receptor in adult rat spinal cord. At all spinal levels, immunoreactivity
      was mainly observed in two narrow crescentic zones bordering the gray matter of
      the dorsal and ventral horns, and around the central canal. In the light
      microscope, this labelling was the densest within the outer part of lamina I
      facing the dorsal column, where it took the form of minute dots and streaks
      scattered in the neuropil. In the electron microscope, such a localization was
      exclusively astrocytic and essentially involved astrocytic leaflets, as indicated
      by the size and irregular shape of the immunostained processes, their location
      between and around neuronal profiles, and their occasional display of glial
      filaments. The diaminobenzidine reaction product showed some predilection for the
      plasma membrane and was occasionally seen at gap junctions of these labelled
      processes. Many labelled astrocytic leaflets were observed in the immediate
      vicinity of axon terminals containing large dense-cored vesicles, and around
      fibres morphologically identifiable as primary afferent, unmyelinated C-fibres.
      These observations suggest that astrocytic neurokinin-2 receptors could define
      the effective sphere of neurokinin A neuromodulation in rat spinal cord, via
      alterations in the regulation of the extracellular environment and glutamate
      uptake by astrocytes and/or the release of putative astroglial mediators. The
      astrocyte neurokinin-2 receptors, activated by extrasynaptic neurokinin A, might
      thus co-operate with neurokinin-1 and neurokinin-3 neuronal receptors in the
      modulation of nociceptive information.

PMID- 9578410
TI  - gp130 cytokines, leukemia inhibitory factor and interleukin-6, induce
      neuropeptide expression in intact adult rat sensory neurons in vivo: time-course,
      specificity and comparison with sciatic nerve axotomy.
AB  - The gp130 cytokines leukemia inhibitory factor and interleukin-6 are neuroactive
      cytokines associated with peripheral nerve injury. Here we show that exogenous
      administration of these factors selectively regulates neuropeptide phenotype in
      intact sensory neurons in a manner consistent with their role as injury-induced
      factors. Intraneural injection of leukemia inhibitory factor into the intact
      sciatic nerve of adult rats induces a significant increase in the percentage of
      neuronal profiles immunoreactive for galanin in the L4 and L5 dorsal root ganglia
      without altering the percentage profiles immunoreactive for vasoactive intestinal
      polypeptide or neuropeptide Y. Galanin-immunoreactivity was predominantly
      confined to those neurons which retrogradely transported and accumulated leukemia
      inhibitory factor. The up-regulation of galanin-immunoreactivity observed in L4
      and L5 dorsal root ganglia following unilateral axotomy of the sciatic nerve was
      significantly reduced following continuous treatment for two weeks with a
      monoclonal antibody against the gp130 receptor motif. Intraneural injection of
      interleukin-6 into the intact sciatic nerve also significantly increased the
      percentage of neuronal profiles which displayed galanin-immunoreactivity but not
      vasoactive intestinal polypeptide or neuropeptide Y-immunoreactivity. Our results
      indicate that cytokines which interact with the gp130 receptor at the site of
      peripheral nerve injury contribute to the cell body response to axotomy. Changes
      in the levels of such cytokines however are insufficient to account for the
      complete repertoire of neuropeptide phenotypic changes associated with peripheral
      nerve injury.

PMID- 9578411
TI  - Bradykinin increases the proportion of neonatal rat dorsal root ganglion neurons
      that respond to capsaicin and protons.
AB  - A number of studies have examined bradykinin-induced sensitization of primary
      afferent neurons to mechanical or thermal stimuli. However, bradykinin-induced
      sensitization to other chemical stimuli has not been systematically addressed. We
      used primary cultures of dorsal root ganglion neurons from neonatal rats to
      determine whether bradykinin alters the responsiveness of individual neurons to
      capsaicin and protons. An increase in the concentration of free intracellular
      Ca2+ was used as a measure of a response to capsaicin or low pH. Pretreatment
      with bradykinin (30 nM) increased the proportion of "intermediate-size" (240-320
      microm2) dorsal root ganglion neurons that responded to capsaicin (100 nM) or low
      pH (6.1). However, among "small-size" (160-239 microm2) neurons, bradykinin
      increased the proportion of neurons that responded to low pH (6.1) but not to
      capsaicin (10 or 100 nM). Because treatment with arachidonic acid (10 microM) did
      not mimic the effect of bradykinin and inhibition of cyclo-oxygenase and
      lipoxygenase with 5,8,11,14-eicosatetraynoic acid (10 microM) did not inhibit the
      effect of bradykinin on the response to capsaicin, it is not likely that the
      bradykinin-induced enhancement of neuronal responsiveness is mediated by
      arachidonic acid or its metabolites in this model. These results support the
      hypothesis that bradykinin sensitizes primary afferent neurons to other chemicals
      such as protons that are present in inflamed tissue, particularly by recruiting
      additional sensory neurons to respond to a given chemical stimulus. An increase
      in the number of responsive nociceptors that innervate inflamed tissue would
      contribute to hyperalgesia via spatial summation on spinal neurons in the pathway
      for pain. Furthermore, since bradykinin enhanced the responsiveness of small-size
      neurons that responded to protons but not to capsaicin, these data suggest that
      bradykinin-induced sensitization to protons and capsaicin occur by different
      mechanisms.

PMID- 9578412
TI  - Role of interleukin (IL)-2 and IL-15 in the tumour progression of a melanoma cell
      line MELP, derived from an IL-2 progressor patient.
AB  - MELP is an interleukin (IL)-2 receptor (IL-2R; alpha+ beta+ gamma-) melanoma cell
      line that was derived, before the beginning of the immunotherapy, from a patient
      whose metastasis increased in size during treatment with IL-2/interferon-alpha.
      In these cells, continuous culture in the presence IL-2 (1000 UI/ml) causes the
      selection of a cell sub-line (termed MILG) expressing the gamma-chain which is
      tumorigenic in nude mice. Here, we further analysed the characteristics of MELP
      and MILG cells as well as clones selected at limiting dilution in the presence of
      high concentrations of IL-2 or IL-15, or those selected after transfection for
      the expression of a human IL-2 transgene (MELP-CL1). MELP cells, but not six
      other melanomas cell lines, shed two soluble immunosuppressive molecules, CD25
      and intercellular adhesion molecule-1, whose levels also strongly increase in
      vivo during immunotherapy. In vitro MELP cells express transcripts for IL-6,
      transforming growth factor, basic fibroblast growth factor and vascular
      endothelial growth factor. Cloning at limiting dilution was obtained in culture
      fed with IL-2 or IL-15. All these clones, as MILG cells, express the transcript
      for the IL-2R gamma chain. This could favour improved interactions with cytokines
      using this chain. By contrast, MELP-CL1 cells, which secrete low amounts of
      biologically active IL-2 (200 UI/10(6) cells) exhibit a phenotype and growth
      characteristics similar to those of the parental MELP cells. Indeed, a
      crosslinking experiment with 125I-IL-2, has showed that MELP and MELP-CL1 cells
      display a scant IL-2 binding ability that is strongly increased in MELP cells fed
      for 1 week with 1000 UI/ml IL-2. These cells, as well as MILG cells express a
      betagamma-complex which can also bind IL-15. IL-2 induces a rapid tyrosine
      phoshorylation in MILG cells, which is followed by a prolonged induction of c-fos
      and c-jun genes. By contrast, in MELP cells IL-2 only causes a delayed induction
      of c-myc gene. All MELP derivatives, but not MILG cells, express the transcripts
      for IL-15, which is not secreted but is present as an intracellular protein. All
      MELP cells express the transcript for the IL-15R alpha chain. MELP-CL1 cells are
      not tumorigenic in nude mice, whereas MILG cells form rapidly growing tumours in
      75% of the mice. Coinjection at the same site of MILG and MELP-CL1 cells causes
      the rapid regression of MILG tumours in 80% of the mice, whereas their bilateral
      injection causes the rapid development of MILG tumours in 100% of the nude mice.
      Finally, treatment in nude mice of MILG cells with low amounts of IL-2 (1000 UI
      per mouse) and IL-15 (50 ng per mouse) induces the development of much more
      aggressive tumours.The expression of functional IL-2Rs in a subset of human
      melanomas could be responsible for tumour progression.

PMID- 9578413
TI  - Transition of horizontal to vertical growth phase melanoma is accompanied by
      induction of vascular endothelial growth factor expression and angiogenesis.
AB  - Melanoma progression in general is characterized by an increase in both
      metastatic frequency and the vascular density of the tumour tissue. Although a
      direct correlation between these two parameters in individual cases seems to be
      lacking, it is clear that metastasis is invariably preceded by angiogenesis. One
      of the angiogenic factors that is produced by human melanoma cells is vascular
      endothelial growth factor (VEGF). To investigate the role of this factor in the
      angiogenic process in primary cutaneous melanoma we determined the mean vascular
      density and the presence of VEGF protein in biopsies of human lesions. The
      results were compared with those found in normal skin or uninvolved skin from
      melanoma patients. In addition, we studied morphological and antigenic features
      of the proliferating neovasculature. We show that (1) the mean vascular density
      gradually rises along with melanoma progression, (2) transition of horizontal to
      vertical growth phase melanoma is accompanied by induction of VEGF protein
      expression and accumulation of this factor in the stroma, (3) vertical growth
      phase melanoma is often organized in nodules separated by septa containing blood
      vessels, but without lymphatics, and (4) blood vessel lumina in vertical growth
      phase melanoma are separated from tumour nodules by two basal lamina containing
      collagen type IV and the endothelium shows activated morphology and focal
      expression of the adhesion molecule E-selectin. Our findings indicate that VEGF
      is a prominent angiogenic factor in melanoma angiogenesis. Although its
      expression is induced during progression, the effect of VEGF on the incidence of
      metastasis is probably indirect.

PMID- 9578414
TI  - Cell differentiation and cell-cycle alterations by tyrosine kinase inhibitors in
      human melanoma cells.
AB  - Differentiation therapy is an attractive option for malignant melanoma, as
      traditional forms of chemotherapy seem to have little effect on this type of
      tumour. Among the several pathways for the experimental induction of
      differentiation of melanoma, we have focused on signal transduction mediated by
      protein kinases. We have examined the effects of calphostin C (a protein kinase C
      inhibitor), genistein and methyl 2,5-dihydroxycinnamate (tyrosine kinase
      inhibitors), and exogenous phosphotyrosine (an activator of protein tyrosine
      phosphatases) on the growth, morphology and differentiation of malignant
      melanomas in vitro. All four compounds tested were able to inhibit cell
      proliferation, but only genistein and methyl 2,5-dihydroxycinnamate were able to
      induce morphological changes, yielding a more dendritic or a rounder phenotype,
      respectively. The latter two drugs were also able to induce specific cell-cycle
      alterations, in contrast to calphostin C and phosphotyrosine. Melanin content was
      increased greatly in phophotyrosine treated cells and, to a smaller extent, in
      cells treated with genistein. RNA expression of specific genes encoding cytolytic
      T-cell antigens was not altered by the two tyrosine kinase inhibitors, in spite
      of the phenotypic changes observed. Together, these results suggest that tyrosine
      kinases are involved in cell cycle, growth, and differentiation pathways in
      malignant melanomas; however, these pathways may not be co-dependent. The results
      also suggest that these pathways may be sensitive to specific tyrosine kinase
      inhibitors or activators of protein tyrosine phosphatases.

PMID- 9578415
TI  - Melanoma cell lines from different stages of progression and their biological and
      molecular analyses.
AB  - The biological and molecular characteristics of cell lines from metastatic
      melanomas have been extensively studied but less is known about cells from the
      biologically earliest stage of primary melanoma. The overall success rate of
      establishing permanent cell lines from such lesions is only 10% of that for
      biologically late primary or metastatic melanomas, although our laboratory now
      has eight cell lines available. The cells are immortal but show reduced or no
      proliferation in soft agar and immunodeficient mice when compared with primary
      melanomas from the biologically advanced vertical growth phase. Metastatic
      melanoma cell lines from patients with familial melanoma or xeroderma pigmentosum
      are biologically similar to those from patients with spontaneous melanomas.
      Irrespective of the malignant stages, deletions and mutations can occur in exons
      1-3 of the p16INK4A gene. DNA fingerprinting was then employed to demonstrate the
      uniqueness of individual cell lines and to confirm the identity of cell lines
      derived from same patients. These cell lines are an excellent resource to
      investigate melanoma progression.

PMID- 9578416
TI  - Lack of antitumour activity of human recombinant tumour necrosis factor-alpha,
      alone or in combination with melphalan in a nude mouse human melanoma xenograft
      system.
AB  - The most promising developments in the field of isolated limb perfusion have
      centred around the use of the recombinant cytokine tumour necrosis factor-alpha
      (rTNF-alpha) in combination with melphalan. While the results of clinical trials
      are impressive, the exact antitumour mechanisms of rTNF-alpha and its role in
      combination with melphalan remain unclear. Our aim was to study the antitumour
      activity of human rTNF-alpha with or without the combination of melphalan in a
      nude mouse human melanoma xenograft system. In a first attempt to define the
      maximal tolerated single dose of rTNF-alpha in this setting, 15 animals were
      exposed to increasing doses of rTNF-alpha (60-2500 microg/kg intraperitoneally).
      All but one animal survived and tumour growth was not influenced by these single
      dose applications of rTNF-alpha even at the very high doses. Anti-tumour activity
      of repeated application of melphalan (three times 9 mg/kg in group 2 and three
      times 6 mg/kg in group 3), of rTNF-alpha alone (nine doses of 50 microg/kg in
      group 4), and of rTNF-alpha in combination with melphalan (nine doses of 50
      microg/kg rTNF-alpha and three times 6 mg/kg melphalan in group 5) was further
      compared with non-treated animals (group 1). Tumour growth was significantly
      inhibited in all animals treated with melphalan (group 2, 3 and 5), but was not
      decreased in animals treated with rTNF-alpha alone (group 4). Mean final tumour
      volumes and mean tumour weight were not different in group 2 (789 +/- 836 mm3,
      0.38 +/- 0.20 g), group 3 (1173 +/- 591 mm3, 0.55 +/- 0.29 g) and group 5 (230 +/
      632 mm3, 0.37 +/- 0.29 g), but significant lower than group 1 (3156 +/- 1512
      mm3, 2.35 +/- 0.90 g) and group 4 (3228 +/- 1990 mm3, 2.00 +/- 1.16 g). There
      were no significant differences between high and low dose melphalan treatment and
      between melphalan treatment in combination with rTNF-alpha. Histological
      examination did not show differences between treated and non-treated animals
      besides slightly inhibited mitotic activities of tumour cells in melphalan
      treated animals. While tumour growth of human xenotransplanted melanoma in nude
      mice could be inhibited by melphalan, we failed to demonstrate any antitumour
      effect of rTNF-alpha. The combination of melphalan and rTNF-alpha did not enhance
      the antiproliferative effect of melphalan alone. Human xenotransplanted tumours
      on nude mice might not be the ideal experimental setting for studies of potential
      direct antineoplastic activity of rTNF-alpha, and these results support the
      concept that TNF-alpha exerts its antitumour activity indirectly, possibly by
      impairing the tumour vasculature and by activating the immune system.

PMID- 9578417
TI  - Molecular basis of T-cell dysfunction in melanoma.
AB  - Human melanoma is an immunogenic tumour which is characterized by a number of
      defined tumour-associated antigens and a specific T-cell-mediated immune
      response. Nevertheless, there is only limited evidence for an effective
      antitumour immune response able to eradicate established melanoma. Thus, the
      existence of an immunologically suppressed state in the tumour-bearing host has
      become an axiom in tumour immunology. There is increasing evidence that
      abnormalities in signal transduction events involved in cell activation are the
      molecular basis for the observed T-cell dysfunction. These abnormalities include
      altered patterns of protein tyrosin phosphorylation, decreased protein levels of
      the Src-family kinases p56(lck) and p59(lyn), and of the CD3zeta chain.
      Furthermore, differences in the expression of transcription factors of the
      nuclear factor NF-kappaB/Rel family have been described.

PMID- 9578418
TI  - Lymphocytes from lymph nodes at different distances from human melanoma vary in
      their capacity to inhibit/enhance tumor cell growth in vitro.
AB  - Eighty-six lymph nodes at measured distances from a primary tumor were removed
      from 68 patients with malignant melanoma. The ability of lymph-node lymphocytes
      (LNL) from these nodes to modulate proliferation of a melanoma cell line (UCLA-SO
      M14) in vitro was tested. LNL from the majority of lymph nodes (66%) inhibited
      M14 growth, but LNL from 34% of nodes stimulated growth of the cell line.
      Peripheral blood mononuclear cells always inhibited M14 growth. Distance of a
      node from the primary tumor was found to be an important determinant of LNL
      activity. This was demonstrated using pairs of nodes from individual patients. In
      86% of cases, LNL from nodes located nearer to the tumor inhibited M14 growth
      less than LNL from more distant nodes. Stimulation of M14 growth was commonest
      with LNL from nodes located near to the tumor. CD8+ T cells were largely
      responsible for M14 growth inhibition, whereas CD4+ cells were associated with
      stimulation of M14 growth. Removal of CD4+ lymphocytes from growth stimulatory
      LNL resulted in a CD4-depleted LNL preparation that inhibited M14 cell
      proliferation. The environment in lymph nodes located dose to tumors may thus
      favor growth of metastatic tumor cells.

PMID- 9578419
TI  - Beta2-microglobulin gene mutations in human melanoma cells: molecular
      characterization and implications for immune surveillance.
AB  - In recent years, the mechanisms underlying defects in the expression/function of
      human leukocyte antigen (HLA) class I antigens have been analyzed in an
      increasing number of melanoma cells, since these abnormalities are likely to have
      a negative impact on T-cell-based immunotherapy of melanoma. This article reviews
      the information about the molecular defects found in melanoma cell lines that do
      not express HLA class I antigens, following a concise description of the
      structure and assembly of HLA class I antigens. Distinct defects ranging from
      large deletions to point mutations in beta2-microglobulin genes have been found
      in melanoma cells. A mutation in an 8 base-pair CT repeat region of exon 1 has
      been found frequently in melanoma cell lines suggesting that this region of the
      beta2-microglobulin gene is a hot-spot for mutations. The effects of beta2
      microglobulin mutations are mostly at the level of translation, emphasizing the
      importance of analyzing beta2-microglobulin expression at the protein level in
      melanoma lesions without detectable HLA class I antigen expression.
      Interestingly, many melanoma cell lines have additional defects that directly
      impact HLA class I antigen expression. Therefore, multiple mechanisms that affect
      the expression/function of HLA class I antigens appear to be available to
      melanoma cells to escape from immune recognition.

PMID- 9578420
TI  - Analysis of the expression of intercellular adhesion molecule-1 and MUC18 on
      benign and malignant melanocytic lesions using monoclonal antibodies directed
      against distinct epitopes and recognizing denatured, non-glycosylated antigen.
AB  - Intercellular adhesion molecule (ICAM)-1 and mucin isotype MUC18 were originally
      identified as melanoma progression antigens by monoclonal antibodies (MAb)
      generated in a search for molecules expressed by melanomas but not detectable on
      benign naevi. As MAb detect single epitopes whose accessibility may be modulated,
      a new panel of antibodies directed against distinct epitopes and reacting with
      denatured nonglycosylated antigen as well as native antigen were used to examine
      expression of these molecules on melanocytic lesions. The antibodies were
      analysed in a binding inhibition assay and divided into groups defining
      independent epitopes. Three anti-ICAM-1 and four anti-MUC18 antibodies
      representing these groups were then tested on frozen sections of 10 benign naevi
      and 10 melanoma lymph-node metastases. The anti-ICAM-1 antibodies demonstrated
      concordant reactivities on both the malignant and benign lesions and reacted with
      all samples suggesting that antibodies that detect differences in ICAM-1
      expression between these two lesions detect altered epitopes. Three of the four
      antibodies directed to MUC18 showed concordant reactivities and indicated that
      this molecule was expressed in nine melanomas and three naevi. However, one
      antibody (MUC18BA.3) reacted strongly with all lesions indicating either
      crossreactivity with another melanocyte molecule or the expression of a different
      form of MUC18 on naevi.

PMID- 9578421
TI  - MAGE-1 expression threshold for the lysis of melanoma cell lines by a specific
      cytotoxic T lymphocyte.
AB  - Human gene MAGE-1 codes for an antigen that is recognized on a melanoma by an
      autologous cytotoxic T lymphocyte (CTL). Because MAGE-1 is expressed on a
      significant proportion of tumours of various histological types and not on normal
      tissues, the encoded antigen may serve as a target for cancer immunotherapy.
      Evaluation of the expression of the gene by reverse transcription polymerase
      chain reaction (RT-PCR) in various tumour samples and tumour cell lines has
      suggested great variability in the level of expression. It was therefore
      important to evaluate the minimal level of expression required for lysis by CTL.
      We tested a number of melanoma cell lines by a quantitative RT-PCR assay to
      correlate their level of MAGE-1 expression and recognition by the relevant CTL
      clone. We found that only cell lines expressing more than 10% of the MAGE-1
      messenger RNA (mRNA) level of reference cell line MZ2-MEL.3.0 (i.e. more than
      three mRNA molecules per cell) were lysed by the CTL or induced significant
      tumour necrosis factor release.

PMID- 9578422
TI  - Expression of HLA class I-specific inhibitory receptors by chronically activated
      cytolytic T lymphocytes: useful or harmful to the host?
AB  - T cells, primarily chronically activated cytolytic T lymphocytes (CTL), can
      express human leukocyte antigen class I-specific inhibitory receptors previously
      identified in natural killer cells. Engagement of these receptors leads to
      inhibition of CTL function. Although the receptor expression may represent a
      safety device to prevent autoimmunity, it may result in the inability to control
      viral spread or tumour growth, i.e. two main functions of CTLs. The
      physiopathologic implications of this event are discussed.

PMID- 9578423
TI  - New tumour-restricted melanoma antigens as defined by cytotoxic T-cell responses.
AB  - Several tumour antigens have been molecularly defined during the last few years
      and three main groups of melanoma-associated antigens have been identified
      according to their pattern of expression. Despite their wide expression in the
      Caucasian population, human leukocyte antigen (HLA) class I-presenting molecules,
      alternate to HLA-A2.1, have received little attention. To further explore the
      complexity of HLA class I-presented melanoma epitopes, we looked for the
      existence of other antigens recognized by T cells in HLA-A3.1 and HLA-A2.1
      restriction. The pattern of recognition identified by HLA-A3.1 or HLA-A2.1
      restricted T-cell lines and clones indicated the existence of a novel category of
      antigens represented by proteins expressed by melanomase but not by melanocytes.

PMID- 9578424
TI  - Immunocytokines: a new approach to immunotherapy of melanoma.
AB  - Targeted interleukin-2 (IL-2) therapy with immunocytokines (i.e. antibody
      cytokine fusion proteins) is effective in eradicating established hepatic and
      pulmonary metastases of melanoma in animal model systems. The effector mechanisms
      responsible for this antitumor effect in syngeneic, immunocompetent mice involves
      mainly CD8+ T cells. This was clearly indicated by immunohistochemical analyses,
      in vivo depletion studies and cytotoxicity tests. Such CD8+ T cells, isolated
      from tumor-bearing mice after immunocytokine therapy, exerted a major
      histocompatibility complex class I-restricted cytotoxicity against the same tumor
      in vitro. Because of this cellular immune response, antibody-directed IL-2
      therapy can even address established metastases displaying extensive
      heterogeneity in the expression of the targeted antigen. The effector mechanisms
      induced by immunocytokines facilitate partial regressions of large subcutaneous
      melanoma exceeding more than 5% of the body weight. These results demonstrate the
      ability of immunocytokines to induce a T-cell-dependent host immune response
      capable of eradicating established melanoma metastases in clinically relevant
      organs and offers an effective, new tool for immunotherapy of malignant melanoma.

PMID- 9578425
TI  - UV-induced N-ras mutations are T-cell targets in human melanoma.
AB  - Human cutaneous melanoma is heterogeneous with respect to the genetic aberrations
      involved and the genes altered are potential targets for the immune system. The
      incidence of cutaneous melanoma is known to be linked to UV peak exposure, and
      the N-ras oncogene is clearly one of the genes involved in the UV carcinogenesis
      in melanoma. It is mutated in a significant proportion of melanomas and therefore
      may serve as a target for T cells. Here, we report that an human leukocyte
      antigen-A2 binding peptide CLLDILDTAGL, encompassing the frequently found 61-Leu
      mutation in N-ras, induces cytotoxic T lymphocytes from healthy donor blood that
      lyse 61-Leu N-ras transfected melanoma cells. Furthermore, we have found an
      association between the presence of N-ras mutations and clinical response to
      immunotherapy with interleukin-2 plus interferon in a group of stage IV melanoma
      patients. Although the overall survival of these patients was not affected by the
      N-ras status of their melanomas, these studies suggest that mutated N-ras may
      provide a target for cytotoxic T lymphocytes in melanoma patients.

PMID- 9578426
TI  - Melanoma and sunscreen use: need for studies representative of actual behaviours.
AB  - Experiments in rodents and humans have shown the ability of sunscreens to prevent
      UVB-induced skin cancers. Sunscreen use has thus become part of the panoply for
      melanoma prevention. However, results from epidemiological investigations
      indicate that sunscreen use could be a risk rather than a protective factor for
      melanoma. This article discusses possible explanations for discrepancies between
      experimental and observational results, suggesting that experiments did not
      reproduce usual human behaviours towards the sunlight. Also, marketing of
      sunscreens fosters unconsidered exposure to sunlight through associating
      sunscreen use to the acquisition of a 'safe suntan', or to the possibility to let
      children go naked into the sunlight without incurring sunburns. It has therefore
      been hypothesized that, because it prevents sunburn, sunscreen use allows
      prolonged exposure to sunlight. If this hypothesis holds, modern sunscreens with
      high protection factor could also represent a threat if their use is motivated by
      the desire of unrestricted exposure to sunlight. To explore this hypothesis, the
      design of a retrospective cohort study is presented, including children 5-7 years
      old, with the total body naevi count as principal endpoint. This study will have
      the opportunity to examine the qualities of modern sunscreens among young
      children.

PMID- 9578427
TI  - A molecular epidemiological approach to the study of expression of a metastasis
      marker in primary melanomas and its correlation with individual patient's risk of
      recurrence or metastasis.
AB  - Tumour cells in malignant melanomas express molecules associated with tumour
      progression; however, up until now, no marker has been able to identify the
      tumour cells from which metastases are derived. It has recently been shown that
      in human melanoma cell lines, populations expressing peanut agglutinin (PNA)
      binding glycoproteins are able to generate metastases, and that such cells do
      exist in primary human melanomas, their presence being associated with the degree
      of local invasion that governs the metastasis risk. To further investigate the
      correlation between the expression of PNA-binding glycoconjugates by cells from
      primary melanomas and the patient's individual risk of recurrence or metastasis,
      a molecular epidemiological approach employing histochemical techniques within a
      case-control design was developed. The main objective of this study is to
      determine whether an histochemical staining with the lectin PNA of cells in the
      primary lesion is associated with an increased risk of local recurrence of
      metastasis, and with survival, independently of Breslow's tumour thickness. The
      study comprises the comparison of the PNA labelling index and of the type and
      intratumour location of the staining as a function of clinical outcome in two
      matched series of patients with known clinical outcome: patients who had died at
      5 years and patients alive at 5 years (to assess association with survival), and
      patients who experienced a recurrence within the first 5 years and patients alive
      without recurrence at 5 years (to assess association with risk of recurrence). A
      matched case-control design was used with a variable number of controls matched
      to each case. Apart from age (+/-5 years), sex and centre where diagnosis was
      made, matching was made on histogenetic type and primary tumour thickness (four
      categories being considered: <0.75, 0.76-1.5, 1.51-3 and >3 mm).

PMID- 9578428
TI  - The current EORTC Melanoma Cooperative Group adjuvant trial programme on
      malignant melanoma: prognosis versus efficacy, toxicity and costs.
AB  - Various adjuvant therapy trials in high risk melanoma are at present ongoing in
      the world. Interferon-alpha (IFN-alpha) and ganglioside vaccines are currently
      being evaluated on both sides of the Atlantic Ocean. In Europe, the two largest
      randomized trials are being carried out by the EORTC Melanoma Cooperative Group.
      In patients with a moderate risk (about 35%) of having micrometastatic disease,
      EORTC trial 18961 will investigate placebo versus vaccination with the
      ganglioside GM2 vaccine (GM2-KLH/QS-21) in 1000 patients with stage IIA melanoma
      (T3N0M0). This trial will be started during spring 1997. In stage IIB-IIIB
      (T4N0M0-TxN1-2M0) patients with a very high risk (about 80%) of having
      micrometastatic disease, EORTC trial 18952 (1000 patients) will investigate
      placebo versus adjuvant therapy with high or low intermediate doses of IFN
      alpha2b (10 MU subcutaneously every day, 5 days per week for 4 weeks, followed by
      either 10 MU subcutaneously, three times weekly for 1 year, or 5 MU
      subcutaneously, three times weekly for 2 years). This review will discuss the
      trials and the philosophy of the programme, which allows more toxic treatments to
      be investigated in patients with a very high risk, and only treatments with
      little or no toxicity to be evaluated in patients with only a modest risk of
      disease. Other recently completed and ongoing trials are also discussed. From all
      programmes it is clear that in the case of medical efficacy, the toxicity, impact
      on quality of life, and costs of the treatment determine whether a treatment will
      be accepted and implemented.

PMID- 9578429
TI  - Polymerase chain reaction detection of circulating tumour cells. EORTC Melanoma
      Cooperative Group, Immunotherapy Subgroup.
AB  - Reverse transcriptase polymerase chain reaction (RT-PCR)-based assays to detect
      occult neoplastic cells offer the highest sensitivity for the study of tumour
      dissemination and minimal residual disease. The detection of small numbers of
      tumour cells in a clinical sample may result in a redefinition of what
      constitutes residual disease and relapse, affecting future patient management.
      However, there remains disparity in the published data on the clinical value of
      RT-PCR for the detection of circulating tumour cells. This most likely reflects
      differences in the methods for sample preparation, RNA extraction, and cDNA
      synthesis among laboratories. Consequently the need for implementation of
      standard quality control measures is pressing in order to facilitate meaningful
      assessment of the methodology and it's clinical value. A 2-day workshop organized
      by the immunotherapy subgroup of the EORTC Melanoma Cooperative Group was held on
      this topic at the Ludwig Institute in Epalinges-sur-Lausanne, Switzerland in
      January 1996, with Stefan Carrel as the local host. Many pertinent issues were
      discussed in great detail, covering every step from sample handling to quality
      control. This workshop resulted in a concerted action leading to the preparation
      of laboratory guidelines, which are summarized in this review.

PMID- 9578430
TI  - Wishful thinking, unicentric empiricism and the everyday world of the medical
      melanomologist.
AB  - Despite the general advances in the chemotherapy of malignancies, progress comes
      slow in the management of patients with disseminated melanoma. Unreflected
      enthusiasm and frustrated scepticism are the scylla and charybdis between which
      the physician tries to choose the right way.

PMID- 9578431
TI  - Secondary prevention of cutaneous malignant melanoma.
AB  - The incidence of cutaneous malignant melanoma continues to increase in most parts
      of the world. Survival rates for melanoma patients show a striking difference
      between those diagnosed with thin primary tumours, and those whose tumours are
      only 2 mm thicker at the time of excision. This fact together with the poor
      response rates to current non-surgical therapies makes a clear case for earlier
      diagnosis and prompt surgical treatment of primary cutaneous malignant melanoma.
      Campaigns aimed at both early diagnosis (secondary prevention) and also at
      primary prevention of cutaneous malignant melanoma are discussed and methods of
      their evaluation considered.

PMID- 9578432
TI  - Anti-melanoma effects of R24, a monoclonal antibody against GD3 ganglioside.
AB  - R24, a mouse monoclonal antibody against GD3 ganglioside, is potent at mediating
      in vitro effector functions such as human complement-mediated cytotoxicity and
      antibody-dependent cellular cytotoxicity, and can block melanoma tumor growth in
      animal models. Because of these properties and the fact that GD3 is abundantly
      expressed on virtually all melanomas but is found on few normal tissues, R24 has
      been tested in a series of clinical trials in patients with metastatic melanoma.
      As a single agent, R24 can induce responses in patients treated with metastatic
      melanoma. Overall, there have been 10 responders out of 103 patients reported;
      two responses have been complete responses. Responses have largely occurred in
      patients treated with intermediate doses of R24 and have included complete
      responses. Combining R24 with either cytotoxic drugs or cytokines has not
      increased this response rate, although one trial with R24 and interleukin-2
      resulted in a 43% response rate and merits further investigation. Local-regional
      treatments R24 (intratumor injections, regional limb perfusion, intrathecal
      administration) have also been attempted in a small number of patients and
      responses have been described. Taken together, multiple centers have reported
      responses in patients with metastatic melanoma treated with R24.

PMID- 9578434
TI  - The search for cell assemblies in the working brain.
AB  - This paper discusses why population ensemble coding by multiple neurons is a
      tenable view of the brain's basic neuronal code. The discussion is based on
      features of neuronal activity in working brains of behaving animals. The key
      concept to elucidate population ensemble coding is the 'cell assembly', i.e.
      overlapped populations of neurons with flexible functional connections within and
      among the populations. Recent examples of experimental approaches which indicate
      the cell-assembly coding of memory in the working brain are given. These
      experiments used a strategy that reveals two main properties of cell assemblies;
      the overlapping of neurons and the dynamic changes of synaptic connections in
      processing different kinds of memory. Several possible features of cell-assembly
      coding that might be explored in future experimental research are enumerated.

PMID- 9578433
TI  - Immunogenicity of CD63 in a patient with melanoma.
AB  - CD63 is a member of the tetraspan family of molecules that is expressed in
      melanoma and which appears to be involved in regulation of motility and adhesion
      of melanoma cells. In the present study we have screened a cDNA library from a
      melanoma cell with antisera from a patient with melanoma and have shown that one
      of the antigens identified was CD63. The clone isolated contained a mutation in
      the transmembrane region, but this did not appear to be involved in
      immunogenicity of the molecule. Antisera from the patient showed weak reactivity
      with CD63 from melanoma and recombinant CD63 in Western blots. The latter studies
      showed marked variation in the fractions of CD63 identified with monoclonal
      antibodies to CD63 consistent with variable glycosylation of CD63. We suggest
      that glycosylation may account for its recognition by the human immune system.
      Further studies are required to assess the role of CD63 as an immunogen in
      melanoma.

PMID- 9578435
TI  - Impairment of working memory in the T-maze after transient global cerebral
      ischemia in the Mongolian gerbil.
AB  - Using a T-maze, the influence of transient global cerebral ischemia on working
      memory in gerbils was investigated. Furthermore, it was examined whether a
      correlation exists between impairment in choice accuracy in the T-maze and neuron
      loss in the hippocampus. In two experiments, male Mongolian gerbils were tested
      in a previously learned delayed alternation T-maze task 1 week after a 4 min
      occlusion of the common carotid arteries. In both experiments memory was
      significantly impaired and in the second experiment, where the design allowed a
      separation between working and reference memory deficits, a selective impairment
      in working memory was seen. The results suggest that ischemia-induced disruption
      of delayed alternation in the T-maze in gerbils is a model which is relevant to
      the clinical manifestations of vascular dementia.

PMID- 9578436
TI  - Prior spontaneous nocturnal waking duration and EEG during quiet sleep in
      infants: an automatic analysis approach.
AB  - To ascertain the role of spontaneous nocturnal waking duration on the EEG
      dynamics during quiet sleep (QS) periods, we analysed the nocturnal polygraphic
      recordings of 12 infants aged 9 47 weeks old. Their sleep was characterised by
      two sleep episodes, separated by spontaneous waking and containing at least two
      QS-paradoxical sleep (PS) cycles each. Automatic analysis of the EEG activity
      recorded by the centro-occipital lead and reflecting the degree of
      synchronisation allowed us to compute a parameter whose values ranged from 0
      (maximum of EEG synchronisation) to 10 (maximum of EEG de-synchronisation). Three
      indicators of the time course of the parameter value were computed during the
      first QS period of the sleep episode subsequent to nocturnal waking: (i) the
      parameter range (difference between the EEG parameter value at the QS onset and
      that at the trough-maximum of EEG synchronisation); (ii) the trough latency (time
      interval between QS onset and trough); and (iii) rate of synchronisation
      (range/trough latency). These three indicators were the dependent variables in a
      multiple regression model, where the independent variables were age and the
      logarithm of the duration of prior waking. The parameter range was correlated
      with the duration of prior waking. Both the trough latency and the rate of
      synchronisation were correlated with age only, respectively, positively and
      negatively. The marked decline in the rate of synchronisation throughout the
      first year of life could account for the failure to find a significant
      correlation between prior waking and the above indicator of the EEG dynamics. The
      relationship between the duration of prior waking and the parameter range in
      following sleep in infants supports the hypothesis of the early emergence of the
      homeostatic regulation of sleep.

PMID- 9578437
TI  - Categorical discrimination of direction in frequency-modulated tones by Mongolian
      gerbils.
AB  - Discrimination of the direction of linearly frequency-modulated tones (FMs) was
      investigated in adult Mongolian gerbils (Meriones unguiculatus) using a footshock
      motivated shuttle box avoidance go/no go procedure. Symmetric pairs of FMs with
      frequency linearly increasing with time (ascending FMs) and with frequency
      linearly decreasing with time (descending FMs) were used as conditioned stimuli,
      CS+ and CS-, respectively. Stimuli were presented in randomized order in daily
      sessions over a period of several months. After a number of sessions, the set of
      conditioned stimuli was changed with respect to frequency range, steepness of
      modulation and duration. In experiment 1, we observed that gerbils could
      discriminate between the ascending 2-4 kHz CS+ and the descending 4-2 kHz CS-
      after a training period of 10-15 days. In experiment 2, we used FM pairs of six
      other frequency ranges in successive sessions (6-13; 1-2; 13-25; 0.5-1; 3 6; 0.25
      0.5 kHz). We found that in the final session the last FM pair (0.25-0.5 kHz) was
      discriminated already after 3-4 days. Experiment 3 showed that the animals were
      able to discriminate five of the FM pairs learned in the separate sessions of
      experiment 2 (i.e. 10 different stimuli) when they were given in randomized order
      during one training session. In experiment 4, novel FM pairs (not heard before)
      and familiar FM pairs (trained in experiments 1-3) were presented within one
      session. It was found that, except for FMs of very short duration and small
      frequency range, novel FMs were discriminated according to their modulation
      direction. These results show that Mongolian gerbils are able to discriminate FM
      tones by modulation direction and, after familiarization with a number of
      different FM pairs, transfer the ascending-descending concept to stimuli not
      heard before.

PMID- 9578438
TI  - Balance in the cat: role of the tail and effects of sacrocaudal transection.
AB  - To determine whether the tail of the domestic cat plays a role in balance during
      locomotion, four cats were trained to traverse a narrow beam. To challenge
      balancing ability, a sudden lateral displacement was imparted to the beam as the
      subject was crossing. Freeze-frame videotape analysis revealed that cats
      responded to beam movement by rapidly moving the tail in the opposite direction.
      Adjustment of the tail contributed to realignment of the hips over the beam and
      enabled the animal to remain aboard the beam. Following complete sacrocaudal
      spinal transection, that eliminated supraspinal control to only the tail, cats
      fell significantly more often in response to movements of the beam. The
      importance of the cat's tail for balance, and the utility of this system for
      modeling functional consequences of spinal cord injury and therapeutic
      interventions, are discussed.

PMID- 9578439
TI  - Facilitation of olfactory recognition by lateral entorhinal cortex lesion in
      rats.
AB  - An original olfactory recognition task was developed in order to examine the
      effect of lateral entorhinal cortex (LEC) lesion on olfactory mnesic processes.
      The task was based on the spontaneous exploratory behavior of rats toward odor
      sources. It consisted of a learning phase during which an odor was presented
      twice and in a recognition test, during which the same odor plus a new one was
      presented. The time rats spent sniffing the odor sources was measured. Olfactory
      recognition was identified by a short investigatory duration for the familiar
      odor as compared to a normal investigatory duration for the new odor during the
      test. The first three experiments aimed to validate the procedure. Experiment 1
      was designed to show the decay of investigatory behavior caused by repeated
      exposure of the rats to one odor. Experiment 2 showed that normal rats display
      recognition when a short (5 or 40 min) pre-test delay was used, but not when a
      long pre-test delay (120 min) was used. Experiment 3 showed that FG7142, a well
      known promnesic drug, enhanced the performance of the rats in this test as it
      allowed recognition at longer pre-test delays. The last experiment aimed at
      testing the effects of aspirative lesion of the LEC. Therefore, LEC-lesioned and
      sham-lesioned rats were submitted to variable pre-test delays. The experiment
      showed that an entorhinal lesion did not produce an impairment, but on the
      contrary facilitated olfactory recognition, as lesioned rats displayed
      recognition for delays at which sham-operated rats did not. These results show
      that LEC lesion apparently prolongs the duration of the olfactory mnesic trace.
      This effect might result from a modification of the functioning of structures
      innervated by the LEC. In this regard, it is noteworthy that LEC lesion produced
      a sprouting of septo-hippocampal fibers in the dentate gyrus of the hippocampus
      as assessed by acetylcholinesterase staining. Although the functional
      significance of this regrowth is not fully understood, the possible role of this
      sprouting should be considered.

PMID- 9578440
TI  - The effects of hippocampal aspiration lesions on conditioning to the CS and to a
      background stimulus in trace conditioned suppression.
AB  - Rats with hippocampal aspiration lesions or cortical control lesions were
      compared to sham operated controls in a trace conditioned suppression task, in
      which a long-lasting background stimulus played the role of more conventional
      contextual cues. In all three surgical treatment groups, conditioning to the
      explicit conditioned stimulus (CS) decreased, but conditioning to the background
      cue increased, when a longer trace interval was used. There was thus no evidence
      of a differential partitioning of associative conditioning as a result of the
      lesion, despite the evident sensitivity of the behavioural paradigm to variations
      in the CS-->unconditioned stimulus (US) interval. This result contrasts with
      earlier reports using conventional contextual cues in analogous experimental
      designs, and so suggests that the sensitivity of contextual conditioning to
      hippocampal dysfunction depends at least in part on the physical nature of
      conventional contextual cues, and not solely on the less precise predictive
      information that such cues typically provide.

PMID- 9578441
TI  - Dissociation of impairment between spatial memory, and motor function and
      emotional behavior in aged rats.
AB  - We investigated changes in learning and memory in aged rats, in relation to motor
      function and emotional behavior. Male Kbl Wistar aged rats (108-weeks-old) were
      divided into two groups, memory impaired and non-impaired, based on performance
      during six training trials in the Morris water maze task. Aged rats with a goal
      latency longer than the mean plus the 99% confidence limit of young rats, were
      regarded as memory impaired, whereas those with a goal latency within the range
      of the 99% confidence limit of the mean of young rats, were considered as memory
      non-impaired. Although the performance of the memory impaired aged rats in the
      standard test of the Morris water maze improved after six re-training trials to
      the level of the non-impaired aged rats and young rats, working memory impairment
      was evident. There were no differences in motor function and emotional behavior
      between the impaired and non-impaired aged rats. These results suggest that
      deficits of learning and memory in memory impaired aged rats can be dissociated
      from changes in motor function and emotional behavior.

PMID- 9578442
TI  - Concurrent administration of subeffective doses of scopolamine and MK-801
      produces a short-term amnesia for the elevated plus-maze in mice.
AB  - Amnesic properties of scopolamine, a muscarinic receptor antagonist, and MK-801,
      a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, were evaluated
      in mice by means of the elevated plus-maze test. In this test, transfer latency,
      the time mice took to move from the open arm to the enclosed arm, was used as an
      index of learning and memory. The 3-day pretreatment training dramatically
      decreased transfer latencies. On the 4th day, the retention trial was performed
      30 min after the intraperitoneal injection of scopolamine (Experiment 1) or MK
      801 (Experiment 2). The doses of 0.25 and 0.5 mg/kg of scopolamine as well as the
      doses of 0.1, 0.15, 0.2 and 0.4 mg/kg of MK-801 significantly prolonged the
      transfer latency as compared with both that in the saline-treated group and that
      measured on the 3rd day. In Experiment 3, subthreshold doses of these two drugs
      given in combination (which were ineffective when given alone: scopolamine 0.25
      mg/kg, MK-801 0.075 mg/kg) significantly prolonged the transfer latency on the
      fourth day. However, an amnesic effect of scopolamine plus MK-801 was transient.
      On the 5th day, no differences in the transfer latency were found. This finding
      clearly indicates that there is a close relationship between cholinergic and
      glutamatergic systems and that both systems play an important role in a spatial
      orientation of mice on the elevated plus-maze.

PMID- 9578443
TI  - Chronic immobilization stress appears to increase the role of dopamine in the
      control of active behaviour in the forced swimming test.
AB  - Previously, we have demonstrated that chronic exposure to immobilization (IMO)
      did not modify the influence of catecholamines on active behaviour of rats in the
      holeboard, but clearly increased the role of these amines in the forced swimming
      test (FST). In the present experiment, it was studied whether or not chronic IMO
      altered the role of dopamine in the two tests. Adult male Sprague-Dawley rats
      were left either undisturbed or subjected daily to 2 h of IMO stress for 12 days.
      On the following day, half of the rats were administered saline and the others
      the dopamine antagonist haloperidol (0.5 mg/kg). Then the rats remained
      undisturbed in the animal room (controls) or were subjected to acute IMO for 2 h.
      Finally, all animals were exposed consecutively to the holeboard (4 min) and the
      FST (5 min). In non-chronically stressed rats, acute IMO depressed behaviour in
      the holeboard but not in the FST. In chronic IMO rats the inhibitory effect of
      acute IMO on holeboard activity was slightly reduced as compared to controls.
      Acute IMO increased struggling in rats previously exposed to chronic IMO but did
      not alter struggling in non-chronically stressed rats. Whereas the inhibition
      caused by haloperidol treatment in the active behaviour of rats in the holeboard
      was not altered by chronic IMO, the inhibitory effect of haloperidol in the
      active behaviour of rats in the FST was greater after chronic IMO, particularly
      in rats also subjected to acute IMO. These data suggest that chronic IMO stress
      potentiates the role of dopamine in a specific behavioural task such as the FST
      and adds support to the previously published data demonstrating enhanced
      behavioural and neurochemical responses to dopamine-related drugs after chronic
      stress.

PMID- 9578444
TI  - Late behavioural and neuropathological effects of local brain irradiation in the
      rat.
AB  - The delayed consequences of radiation damage on learning and memory in rats were
      assessed over a period of 44 weeks, commencing 26 weeks after local irradiation
      of the brain with single doses of X-rays. Doses were set at levels known to
      produce vascular changes alone (20 Gy) or vascular changes followed by necrosis
      (25 Gy). Following T-maze training, 29 weeks after irradiation, irradiated and
      sham control groups performed equally well on the forced choice alternation task.
      When tested 35 weeks after irradiation, treated rats achieved a much lower
      percentage of correct choices than controls in T-maze alternation, with no
      difference between the two irradiated groups. At 38-40 weeks after irradiation,
      rats receiving both doses showed marked deficits in water maze place learning
      compared with age-matched controls; performance was more adversely affected by
      the higher dose. The extent of impairment was equivalent in the two groups of
      rats irradiated with 25 Gy, those trained or not previously trained in the T
      maze, suggesting that water maze acquisition deficits were not influenced by
      prior experience in a different spatial task. In contrast to water maze
      acquisition, rats irradiated with 20 Gy showed no deficits in working memory
      assessed in the water maze 44 weeks after irradiation, whereas rats receiving 25
      Gy showed substantial impairment. Rats receiving 25 Gy irradiation showed marked
      necrosis of the fimbria and degeneration of the corpus callosum, damage to the
      callosum occurring in animals examined histologically 46 weeks after irradiation,
      but in only a third of the animals examined at 41 weeks. However, there was no
      evidence of white matter necrosis in rats irradiated with 20 Gy, examined 46
      weeks after irradiation. These findings demonstrated that local cranial
      irradiation with single doses of 20 and 25 Gy of X-rays produced delayed
      impairment of spatial learning and working memory in the rat. The extent of these
      deficits appears to be task- and dose-related, since rats treated with 25 Gy
      showed marked impairments in all measures, whereas rats treated with the lower
      dose showed less impairment in water maze learning and no deficits water maze
      working memory, despite significant disruption of working memory in the T-maze.
      The findings further suggest that although high dose irradiation-induced white
      matter necrosis is associated with substantial impairment, cognitive deficits may
      also be detected after a lower dose, not associated with the development of
      necrosis.

PMID- 9578445
TI  - The effects of queenlessness on the maturation of the honey bee olfactory system.
AB  - During the first week of adult life the olfactory system of the honey bee
      undergoes a critical period of maturation [Masson and Arnold, Organisation and
      plasticity of the olfactory system of the honeybee, Apis mellifera, in: Menzel
      and Mercer (Eds.), Neurobiology and Behaviour of Honeybees. Springer-Verlag,
      Berlin, 1987, pp. 280 295]. This is accompanied by dramatic increases in the
      volume of the antennal lobes [Winnington et al., Structural plasticity of
      identified glomeruli in the antennal lobes of the adult worker honey bee. J.
      Comp. Neurol., 365 (1996) 479-490], centres of the brain that receive direct
      input from primary olfactory receptor neurons housed in the antennae of the bee.
      Here, we show that during the first 4-6 days of adult life there is a significant
      increase in the percentage of bees that respond to a conditioned olfactory
      stimulus after a single conditioning trial and, furthermore, that the ontogeny of
      this olfactory learning behaviour is altered significantly if the queen is
      removed from the colony. The absence of a queen during early adult life also has
      site-specific effects on the maturation of the antennal lobes of the brain. These
      results show for the first time that the queen's presence in a colony has a
      significant impact not only on the behaviour of the adult worker honey bee, but
      also on the structure of the brain.

PMID- 9578446
TI  - Possible regeneration of rat medial frontal cortex following neonatal frontal
      lesions.
AB  - The experiments described here show that the cavity left by midline frontal
      cortex removals at 10 days of age (P10) fills in with neural tissue. Similar
      changes are not found at earlier and later ages. This neuronal filling is blocked
      by prior pretreatment by administration of Bromodeoxyuridine (BrdU) on embryonic
      day 13. Administration of BrdU following the P10 lesion does not interfere with
      regrowth. Subsequent immunohistochemical staining for BrdU demonstrates the
      regrown area to be composed of newly generated cells. which include pyramidal and
      nonpyramidal neurons. Injections of a retrograde tracer into the striatum or
      posterior parietal cortex shows that the new neurons have connections similar to
      those of undamaged brains. The regrowth of this tissue is correlated with
      recovery of function in a test of forelimb use. Thus, the mammalian brain, during
      some privileged postnatal stages of growth. is capable of extensive
      reorganization that includes regeneration of lost neurons. These results are
      discussed in relation to the proximity of the lesion to the stem cells in the
      lateral ventricle and their postnatal migrational activities.

PMID- 9578447
TI  - Cerebral morphology and functional sparing after prenatal frontal cortex lesions
      in rats.
AB  - Rats were given suction lesions of the presumptive frontal cortex on embryonic
      day 18 (E18) and subsequently tested, as adults, on tests of spatial navigation
      (Morris water task, radial arm maze), motor tasks (Whishaw reaching task, beam
      walking), and locomotor activity. Frontal cortical lesions at E18 affected
      cerebral morphogenesis, producing unusual morphological structures including
      abnormal patches of neurons in the cortex and white matter as well as neuronal
      bridges between the hemispheres. A small sample of E18 operates also had
      hydrocephaly. The animals with E18 lesions without hydrocephalus were
      behaviorally indistinguishable from littermate controls. The results demonstrate
      that animals with focal lesions of the presumptive frontal cortex have gross
      abnormalities in cerebral morphology but the lesions leave the functions normally
      subserved by the frontal cortex in adult rats unaffected. The results are
      discussed in the context of a hypothesis regarding the optimal times for
      functional recovery from cortical injury.

PMID- 9578448
TI  - Lateralization of detour behaviour in poeciliid fish: the effect of species,
      gender and sexual motivation.
AB  - We studied detour responses of two species of poeciliid fish (Gambusia hoolbroki
      and Girardinus falcatus) faced with a vertical-bar barrier, through which
      conspecifics of the same or different sex or a simulated-predator (which induced
      detour behaviour for predator-inspection responses) were visible. Both species
      showed a consistent bias to turn leftward when faced with the predator, and a
      consistent bias to turn rightward when faced with an opaque barrier. Sexual
      stimuli (conspecifics of different sex) elicited a leftward bias in females that
      had been deprived of the presence of males for 2 months, whilst no bias was
      apparent in non-deprived females. Social stimuli (conspecifics of the same sex)
      elicited a consistent rightward bias in females but not in males in both species.
      Results suggest that males and females of both species show basically the same
      pattern of laterality and that sex differences, when present, can be accounted
      for in terms of differences in sexual and/or social motivation.

PMID- 9578449
TI  - Timed active avoidance learning in lurcher mutant mice.
AB  - Lurcher mutant mice (+/Lc) which exhibit a massive loss of neurons in the
      cerebellar cortex and in the inferior olivary nuclei were subjected to an active
      avoidance learning task; the animals' avoidance response must occur within a
      small time window after a short or a long delay. The control mice needed a mean
      of 8.3 sessions of 10 trials (short delay group) and of 11.8 sessions (long delay
      group) and showed good retention after a 24 h interval. When subjected to the
      same number of sessions, the +/Lc mice were unable to learn the timing task.
      However, a subgroup of lurcher mutants was able to learn after a high number of
      sessions (25.4 sessions as a mean). There was no intergroup difference in the
      standard version of one-way active avoidance. These results indicate that the
      cerebellar cortex is involved in time processing during active avoidance. The
      cerebellum may be part of a loop including the cerebral cortex known to be
      involved in time perception. An alternative explanation is that the cerebellar
      mutant animals had persevering tendencies acquired during performance of the one
      way avoidance task.

PMID- 9578450
TI  - Conditioned 'prehension' in the pigeon: kinematics, coordination and stimulus
      control of the pecking response.
AB  - Like human prehensile behavior, the pigeon's ingestive pecking response is
      elicited by visual stimuli conveying information about the location and size of
      the target. This information is used to generate localized ingestive pecks whose
      gapes are amplitude-scaled to seed size, prior to contact. We employed high
      resolution, 'real-time' monitoring of head acceleration, jaw movements and
      terminal peck location to examine the kinematics, coordination and stimulus
      control of conditioned pecking. Conditioning procedures were used to bring
      pecking under the control of visual targets whose stimulus properties (size,
      location) were independently varied, while simultaneously monitoring pecking
      response parameters. Stimulus control of the transport component (peck
      localization) is extremely precise, even in the absence of a specific
      localization-dependent reinforcement contingency. Subjects also showed amplitude
      scaling of gape size to the size of a visual target, but over a more restricted
      range than shown to food pellets of comparable sizes. Comparison of the kinematic
      profiles of conditioned and ingestive pecks suggests that conditioned pecking is
      functionally analogous to human 'pointing' rather than 'grasping' behavior.

PMID- 9578451
TI  - Extracellular serotonin in the striatum increased after immobilization stress
      only in the nighttime.
AB  - The release of serotonin (5-HT) in the striatum and the motor activity of rats
      given the immobilization stress were measured using in vivo microdialysis
      techniques and locomotion counts. Serotonin release in the striatum did not
      change in the daytime and nighttime, but motor activity in the nighttime was
      significantly higher than in the daytime. Serotonin release was not significantly
      increased during immobilization stress in the daytime or nighttime. In the
      nighttime, however, after the end of stress, 5-HT release was significantly
      increased from 0.002 ng/dialysate to 0.47 ng/dialysate. The motor activities were
      also significantly increased after the stress in the nighttime. These results
      suggest that the effects of immobilization stress on serotonin release in the
      striatum were different in the daytime and nighttime. In the nighttime, serotonin
      release in the striatum and the motor activities increased not during but after
      immobilization stress.

PMID- 9578452
TI  - Postnatal development of EEG patterns, catecholamine contents and myelination,
      and effect of hyperthyroidism in Suncus brain.
AB  - The postnatal development of the central nervous system (CNS) in house musk shrew
      in the early stage of maturation was studied. The electroencephalogram (EEG) and
      visual evoked potential (VEP) in association with catecholamine contents and
      myelin basic protein (MBP) immunoreactivity were carried out from the 1st to the
      20th day of postnatal age. Different EEG patterns which were specific to
      behavioral states (awake and drowsy) were first recorded on the 5th day, and the
      total power which was obtained by power spectrum analysis increased after this
      stage. The latencies of all peaks in VEP markedly shortened between the 5th and
      the 7th day. Noradrenalin (NA) content of the brain showed a slight increase
      after the 3rd day, and reached maximum levels on the 7th day, which was delayed a
      few days compared to dopamine (DA). In hyperthyroidism, the peak latency of VEP
      was shortened and biosynthesis of NA in cerebral cortex and DA in hippocampus was
      accelerated. The most obvious change in MBP-immunoreactivity of the telencephalon
      occurred from the 7th to the 10th day. These morphological changes in the brain
      advanced at the identical time-course to those in the electrophysiological
      development and increment of DA and NA contents.

PMID- 9578453
TI  - Importance of the medial amygdala in rat penile erection evoked by remote stimuli
      from estrous females.
AB  - Effects of medial amygdala lesions (MAL) were examined on rat penile erection in
      three different experimental situations. Only sexually vigorous males, as
      identified by preoperative mating tests, were used. Bilateral radiofrequency
      lesions were confined to the posterior medial amygdala, with little systematic
      damage to anterior medial amygdala or to adjacent structures. Lesion electrodes
      were withdrawn without current application in sham-operated animals (SHAM). After
      recovery for brain surgery, males were tested for (1) noncontact erection (NCE)
      that occurs when males were placed in proximity to inaccessible estrous females,
      (2) reflexive erection evoked in supine males by retraction of the penile sheath,
      and (3) copulatory behaviour with receptive females. In the NCE test, none of the
      MAL males showed penile erection during the 20 min observation, whereas 70% of
      the SHAM males showed it (P < 0.001). In contrast, no erectile dysfunction in the
      MAL males was detected in the other two tests. MAL males displayed more penile
      body erections (flips) than SHAM males in the reflexive-erection test (P <0.05).
      In the copulation test, most of the MAL males achieved intromission, but their
      intromission ratio, a partial measure of erectile function, was marginally lower
      than that of SHAM males (P = 0.051). MAL males had longer intervals between
      intromissions (P < 0.001); as a result, none of them ejaculated during the 30 min
      period that followed the first intromission. The results suggest that the
      posterior medial amygdala plays an essential role in the regulation of NCE, and
      it may also contribute to the regulation of erection in other contexts.

PMID- 9578454
TI  - Atomic mutations in annexin V--thermodynamic studies of isomorphous protein
      variants.
AB  - We have recently developed methods for specific and high-level replacement of
      methionine with 2-aminohexanoic acid, selenomethionine and telluromethionine as
      isosteric and atomic analogues for structural investigations of human recombinant
      annexin V. The variants formed isomorphic crystals and retained the parent three
      dimensional fold and bioactivities. Folding parameters were determined from
      thermal and chemical unfolding to partially denatured states. Stabilities
      estimated from guanidinium chloride unfolding equilibria are not changed
      significantly for the atomic mutants (S-->Se-->Te) while the denaturation
      midpoint is shifted toward lower values with an increase of the m values at the
      increase of hydrophobicity. In contrast, stabilities in urea are considerably
      affected by the atomic substitutions, decreasing together with the m and [D]1/2
      values. The methylene and selenium variants are identical within the limits of
      error of all measurements performed here. The physical parameters of the amino
      acid analogues and the values derived from the slopes of the unfolding data are
      highly correlated. This approach demonstrates how systematic variations in atomic
      number at the site of replacement (atomic mutations) can provide a method to
      probe specific folding properties of proteins.

PMID- 9578455
TI  - Phosphorylation of ethanolamine, methylethanolamine, and dimethylethanolamine by
      overexpressed ethanolamine kinase in NIH 3T3 cells decreases the co-mitogenic
      effects of ethanolamines and promotes cell survival.
AB  - Ethanolamine (Etn), as well as its N-methyl (MeEtn) and N,N-dimethyl (Me2Etn)
      analogues, were recently shown to potentiate the stimulatory effect of insulin on
      DNA synthesis in serum-starved NIH 3T3 fibroblasts. In the present work we
      assessed the impact of the co-mitogenic effects of Etn and its methyl analogues
      on cell proliferation and cell survival, and examined whether the cell growth
      regulatory effects of these ethanolamines involve an Etn-kinase-mediated
      phosphorylation step. For this purpose, NIH 3T3 sublines highly overexpressing
      Drosophila Etn kinase and an appropriate vector control line were utilized and
      the effects of Etn, MeEtn, Me2Etn, methylamine (MeNH2), and dimethylamine (Me2NH)
      were studied. 31P-NMR analysis of the water-soluble cell metabolites revealed
      that both MeEtn and Me2Etn, but not choline, are excellent substrates for the
      expressed Etn kinase. The methylated ethanolamines (MeEtn and Me2Etn) and
      methylamines (MeNH2, Me2NH) were used as Etn models that can or cannot be
      phosphorylated, respectively. In serum-starved vector control cells, both MeNH2
      (1 mM) and Me2NH (1 mM) were more effective than Etn in enhancing insulin-induced
      DNA synthesis, and both were almost as effective as MeEtn and Me2Etn. However, in
      the Etn kinase overexpressor cells the potentiating effects of Etn, MeEtn and
      Me2Etn, but not those of MeNH2 and Me2NH, were significantly reduced. Moreover,
      in the overexpressor cells, lower concentrations of Etn (50-200 microM) inhibited
      the combined mitogenic effects of Me2NH (1 mM) and insulin. These data are
      consistent with a mechanism in which the phosphorylated and non-phosphorylated
      ethanolamines are negative and positive regulators of insulin-induced
      mitogenesis, respectively. After incubating the cells for 13 days in serum-free
      medium in 96-well microplates, there was a steady decrease in cell numbers in
      both cell lines. However, between 6-13 days, 0.1-1 mM MeEtn and, particularly,
      Me2Etn provided significant protection against cell death in the Etn kinase
      overexpressor cells. In vector control cells, only Me2Etn in combination with
      insulin had similar effects on cell survival. The data suggest that
      phosphorylated ethanolamines may function as promoters of cell survival.

PMID- 9578456
TI  - Expression and characterization of three tomato 1-aminocyclopropane-1-carboxylate
      oxidase cDNAs in yeast.
AB  - Heterologous expression in yeast has previously shown that the tomato cDNA LE
      ACO1 encodes a functional 1-aminocyclopropane-1-carboxylate (ACC) oxidase (ACO)
      protein [Hamilton, A. J., Bouzayen, M. & Grierson, D. (1991) Proc. Natl Acad.
      Sci. USA 88, 7434-7437]. In the present work, full-length cDNAs encoding the two
      other members of the tomato ACO family (LE-ACO2 and LE-ACO3) were isolated and
      expressed in Saccharomyces cerevisiae. Analysis of the predicted amino acid
      sequences showed that the ACO1 and ACO3 proteins are highly similar (95%) while
      ACO2 is more divergent (89%). Yeast strains transformed with each of the three
      cDNAs were able to convert exogenous ACC to ethylene, the ACO1 strain exhibiting
      the highest activity in vivo and the ACO3 and ACO2 strains reaching 65% and 45%
      of ACO1 maximum activity, respectively. None of the ACO activities expressed in
      yeast required addition of ascorbate in vivo. ACO activities assayed in vitro
      revealed no significant differences between the three isoforms with regards to
      optimum temperature (29 degrees C), optimum pH (6.8-7.2), absolute dependence for
      ascorbate, Fe2+ and carbon dioxide, and inhibition by iron-chelating agents (1,10
      phenanthroline and EDTA), Co2+ and free-radical scavengers (n-propyl gallate).
      However, differences were detected in the apparent Km values for ACC, the pI and
      the specific activity. The biochemical features that might explain the
      differences between the isoenzyme activities are discussed.

PMID- 9578457
TI  - Isolation and characterization of the cDNA and the gene for eukaryotic
      translation initiation factor 4G from Drosophila melanogaster.
AB  - Recent evidence supports the notion that the eukaryotic polypeptide chain
      initiation factor (eIF)4G plays a critical bridging role in coordinating other
      eIF involved in eukaryotic translation initiation. Here we report the isolation
      and characterization of a 5621-bp cDNA encoding Drosophila eIF4G. The longest ORF
      predicts a polypeptide of 1666 amino acids with a molecular mass of 183,940 Da
      and shares 25% amino acid identity with other eIF4G. The 5' untranslated region
      is 386 nucleotides long and contains seven AUG codons out of frame. The in vitro
      transcription/translation of the cDNA yielded a major polypeptide, which was
      specifically immunoprecipitated with an antibody against Drosophila eIF4G. This
      polypeptide has the same electrophoretic mobility as eIF4G purified from
      Drosophila melanogaster embryos. A conserved eIF4E-binding motif was found in
      Drosophila eIF4G. The gene maps at the 102E region of chromosome 4 and spans a
      genomic region of approximately 16 kb. It was found to contain 15 introns. A
      single RNA transcript of approximately 5.9 kb was detected by northern blotting
      of poly(A)-rich RNA prepared from Drosophila adults. The sequence upstream of the
      transcription initiation site lacks the consensus TATA box, but contains several
      sequences possibly involved in the regulation of transcription.

PMID- 9578458
TI  - Two vascular apoptosis-inducing proteins from snake venom are members of the
      metalloprotease/disintegrin family.
AB  - Hemorrhagic snake venom induces apoptosis in vascular endothelial cells. In a
      previous report, we described the purification of a vascular apoptosis-inducing
      protein (VAP) from Crotalus atrox [Masuda, S., Araki, S., Kaji, K. & Hayashi, H.
      (1997) Biochem. Biophys. Res. Commun. 235, 59-63]. We report here the
      identification of a second vascular apoptosis-inducing protein, VAP2, in venom
      from C. atrox. When we fractionated crude venom from C. atrox by isoelectric
      focusing, we found two proteins with apoptosis-inducing activity, one was basic
      and the other acidic. The basic protein corresponded to VAP, and we named the
      acidic protein VAP2. VAP2 was a monomeric protein with molecular mass of 55 kDa
      and an isoelectric point of 4.5. VAP2 killed vascular endothelial cells in
      culture, and the death of cells exhibited the characteristic features of
      apoptotic activity of VAP2 seemed to be specific to endothelial cells, as
      reported for VAP. The half-lethal doses of VAP and VAP2 were 0.3 microg/ml and
      0.1 microg/ml, respectively. Analysis of the partial amino acid sequences of VAP
      and VAP2 revealed similarities to members of the metalloprotease/disintegrin
      family. The sensitivity of VAP2 to changes in pH and temperature was distinct
      from that of VAP. Our results suggest that VAP and VAP2 are members of the
      metalloprotease/disintegrin family.

PMID- 9578459
TI  - Molecular cloning of cDNAs and expression of mRNAs encoding alpha and beta
      subunits of soluble guanylyl cyclase from medaka fish Oryzias latipes.
AB  - Two cDNA clones encoding alpha and beta subunits of soluble guanylyl cyclase (GC)
      were isolated from medaka fish (Oryzias latipes) cDNA libraries and designated as
      OlGCS-alpha1 and OlGCS-beta1, respectively. The ORF of OlGCS-alpha1 encodes 678
      amino acids and that of OlGCS-beta1 encodes 614 amino acids. Both subunits have a
      putative catalytic domain conserved with membrane GC and adenylyl cyclases. The
      amino acid sequences of OlGCS-beta1 and mammalian soluble GC subunits are highly
      conserved throughout the entire protein, suggesting that amino acid sequences
      outside the catalytic domain are important for the functioning of the beta
      subunit. On the contrary, amino acid sequences of alpha subunits outside the
      catalytic domain are fairly divergent between fish and mammals. Reverse
      transcription/PCR (RT/PCR) analysis showed that OlGCS-alpha1 and OlGCS-beta1
      transcripts were abundant in the brain, eye, spleen and testis. RT/PCR analysis
      demonstrated that both transcripts were present in unfertilized eggs, were
      reduced immediately after fertilization, then increased again. In addition, our
      results suggest that expression patterns of OlGCS-alpha1 and OlGCS-beta1 genes
      are different from each other both during development and in adults.

PMID- 9578460
TI  - Inactivation and destruction of conserved Trp159 of Fe-superoxide dismutase from
      Porphyromonas gingivalis by hydrogen peroxide.
AB  - The superoxide dismutase (SOD) of Porphyromonas gingivalis, an obligate anaerobe,
      was purified from Escherichia coli (sodA sodB mutant) harboring the P. gingivalis
      SOD-encoding gene. The purified protein contained both iron and a small amount of
      manganese. Iron- and manganese-reconstituted SOD, which contained one of these
      metals exclusively, showed specific activities of 1000 and 1200 U/mg/mol of
      metals/subunit, respectively. These values were similar to the specific activity
      of the native enzyme purified from the recombinant E. coli strain. The Fe
      reconstituted enzyme was inactivated by 10 mM hydrogen peroxide to about 5% of
      its original activity after a 15 min incubation at 25 degrees C at pH 7.8,
      whereas the Mn-reconstituted enzyme showed no inactivation after 80 min. A
      concomitant increase in absorbance at 320 nm was observed with inactivation of
      the Fe-reconstituted enzyme. Amino acid analysis of the inactivated Fe
      reconstituted enzyme showed a decrease of about 0.7 residues of
      tryptophan/subunit, a value similar to the iron content of the iron-reconstituted
      enzyme. Three major peptides of the digests of the purified SOD with
      lysylendopeptidase were separated by a reverse-phase HPLC monitoring at 280 nm.
      One of the peptides, corresponding to the residues from Gly149 to Lys176,
      decreased in the HPLC eluent of the H2O2-inactivated SOD to 20% of the amount
      measured for native SOD. Since this peptide contains only one tryptophan residue,
      it was concluded that the decomposed tryptophan residue is Trp159, which is
      located midway between the third and fourth metal ligands, Asp157 and His161, and
      is conserved in aligned amino acid sequences of all known Fe-SODs and Mn-SODs.
      Based on these results, we propose that the differences in hydrogen peroxide
      sensitivities observed for the Fe-SODs and Mn-SODs may be caused by the
      difference in the identity of the active site metal in the Fe-SODs and Mn-SODs
      and a tuning of the properties of the iron center in the Fe-SODs.

PMID- 9578461
TI  - Ca2+ and Zn2+ bind to different sites and induce different conformational changes
      in human calcyclin.
AB  - Calcyclin (CaCY) is a member of the S100 subfamily of helix-loop-helix (EF-hand)
      calcium-binding proteins. Human CaCY was overexpressed in Escherichia coli and
      purified with an overall yield of 40 mg/l culture. Ca2+ and Zn2+ binding
      properties of CaCY were examined with respect to the oxidation state of the
      single Cys residue at position 3. CaCY with the SH group either reduced, blocked
      or oxidized stays as a dimer as shown by analytical ultracentrifugation. Upon
      binding of Ca2+, CaCY exhibits 30% enhancement of the Tyr fluorescence, the
      apparent binding constant (Ka) being 2.8-5.8x10(4) M(-1). Oxidized CaCY binds
      Ca2+ approximately twice as weakly than its reduced form. The affinity for Ca2+
      is increased in the presence of caldesmon, which could be a potential target
      molecule. Fully reduced CaCY binds Zn2+ with an affinity of at least 1.0x10(7) M(
      1). As compared to Ca2+, Zn2+ binding results in a three times greater
      enhancement of the Tyr fluorescence. Saturation occurs at a Zn2+/CaCY ratio of
      2:1. The reactivity of Cys3 is reduced by Zn2+ binding, although oxidized CaCY
      still binds Zn2+. On the basis of the effects of thiol-directed labels on the
      affinities for Ca2+ and Zn2+, the fluorescence changes accompanying the binding,
      and the CaCY reactivity with a hydrophobic probe, it was concluded that the two
      cations bind to CaCY at different sites: Ca2+ binds probably at the EF-hand type
      sites, whereas binding of at least one Zn2+ ion involves the Cys residue, and
      results in a different structural change.

PMID- 9578462
TI  - Activation of the precursor of human stromelysin 2 and its interactions with
      other matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMP) are synthesized as inactive zymogens (proMMP) and
      subsequently activated by many factors to degrade the extracellular matrix (ECM).
      In the present study, we have examined the intermolecular activation mechanisms
      of proMMP by MMP-10 (stromelysin 2). ProMMP-10 was purified from the culture
      media of OSC-20 human oral squamous carcinoma cells stimulated with 12-O
      tetradecanoylphorbol 13-acetate. The final products are partially activated
      (approximately 38% of the full activity) during the purification steps and
      contain proMMP-10 of Mr 56,000 with minor protein bands of Mr 47,000, 24,000 and
      22,000. The zymogen is activated by 4-aminophenylmercuric acetate and processed
      to the active forms of Mr 47,000 and 24,000. The NH2-terminal sequence of the
      47,000- and 24,000-Mr species is Phe82-Ser-Ser-Phe-Pro-Gly, which is identical to
      that of stromelysin 2. ProMMP-9 (progelatinase B) is activated by MMP-10 to its
      full activity and processed to the low-Mr species of Mr 81,000, 65,000, 57,000
      and 55,000, the former two of which show proteolytic activity on a gelatin
      zymography. The NH2-terminal sequence analysis indicates that the 81,000-, 65,000
      and 57,000-M, species have the identical sequence of Phe88-Gln-Thr-Phe-Glu-Gly,
      suggesting the cleavage of the Arg87-Phe88 peptide bond for activation and both
      NH2-terminal and COOH-terminal truncation in the 65,000- and 57,000-Mr forms. MMP
      10 also activates proMMP-7 (promatrilysin) up to about 60% of the full activity
      and generates the same active species of Mr 19,000 as that obtained by activation
      with 4-aminophenylmercuric acetate. Incubation of proMMP-2 (progelatinase A) or
      proMMP-3 with MMP-10 does not result in activation of these proMMP. These results
      indicate that in addition to the previously reported activation of proMMP-1
      (tissue procollagenase) and proMMP-8 (neutrophil procollagenase), MMP-10 can also
      activate proMMP-9 and proMMP-7, and suggest the possibility that MMP-10 may
      replace a role of MMP-3 in the ECM degradation in concert with other MMP under
      various pathological conditions.

PMID- 9578463
TI  - Enzymatic activity of two caspases related to interleukin-1beta-converting
      enzyme.
AB  - Interleukin-1beta-converting enzyme is a member of a family of human cysteine
      proteases with specificity for aspartic acid, which have been named caspases.
      Within this family of enzymes, transcript X (TX) and transcript Y (TY) (caspases
      4 and 5, respectively) are very similar to ICE (caspase 1) and form the ICE
      subfamily. Given the high degree of conservation in the sequences of these
      proteases (more than 50% amino acid identity in the mature enzymes), it was of
      interest to examine whether they shared similar substrate specificities. The
      three enzymes, ICE, TX and TY, were therefore expressed in baculovirus-infected
      insect cells, as 30-kDa proteins lacking the propeptide. Automaturation into p20
      and p10 subunits occurred within the cells. Active ICE, TX and TY were collected
      in the cell culture supernatants. In addition, their production induced the
      activation of an endogenous 32-kDa putative cysteine protease (CPP32) like
      caspase. T7-tagged ICE, TX and TY were purified by immunoaffinity and tested for
      their catalytic efficiency on YVAD-containing synthetic substrates and on the ICE
      natural substrate, pro-interleukin-1beta. TX cleaved the same synthetic
      substrates as ICE (Km of 90 microM and k(cat) of 0.4 s(-1) for Suc-YVAD-NH-Mec,
      where Suc represents succinyl and NH-Mec represents amino-4-methylcoumarin) and
      could cleave pro-interleukin-1beta into the same peptides as ICE but less
      efficiently. On the other hand, TY showed very little efficacy on the different
      ICE substrates (Km of 860 microM for Suc-YVAD-NH-Mec). These results show that
      the ICE/TX/TY subfamily has functional heterogeneity and that ICE remains the
      preferred enzyme for pro-interleukin-1beta cleavage.

PMID- 9578464
TI  - Bilitranslocase can exist in two metastable forms with different affinities for
      the substrates--evidence from cysteine and arginine modification.
AB  - Bilitranslocase is an organic anion carrier involved in bilirubin and phthalein
      uptake by the liver. In rat liver plasma membranes, its function is assayed by
      recording the electrogenic sulfobromophthalein movement. This has been found to
      be inhibited by both cysteine-specific and arginine-specific reagents. Inhibition
      is both partial and it occurs to the same extent, i.e. approximately 50%. The
      effects are not additive. Here we describe the mechanism underlying the above
      observations. It is concluded that bilitranslocase occurs in two possible states,
      featured by high and low affinity for the substrates (for sulfobromophthalein, Km
      = 5 microM and 37 microM, respectively). Cysteine- or arginine-reactive reagents,
      by reacting selectively with the low-affinity form, entrap it and shift the
      equilibrium between the two forms, so that, at completion, only the low-affinity
      form is present. The substrate concentration in the standard transport assay is
      39 microM, a value at which the modified low-affinity form operates in the range
      of half-maximal velocity. This explains both the apparent half-inhibition
      measured after the chemical treatments and the lack of additivity. In addition,
      the substrates are shown to enhance the rate of conversion from the low-affinity
      to the high-affinity form of the translocator, thus favouring its high-affinity
      form under physiological conditions.

PMID- 9578465
TI  - Repression of phosphoenolpyruvate carboxykinase gene activity by insulin is
      blocked by 3-aminobenzamide but not by PD128763, a selective inhibitor of
      poly(ADP-ribose) polymerase.
AB  - Expression of the phosphoenolpyruvate carboxykinase (PEPCK) gene is induced by 3
      aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase. Synthesis of PEPCK
      mRNA is repressed by insulin, but remains detectable in H4IIE hepatoma cells
      exposed simultaneously to both 3-aminobenzamide and insulin. This capability of 3
      aminobenzamide to block the inhibitory actions of insulin suggests that ADP
      ribosylation is required for the regulation of PEPCK gene expression by insulin.
      Furthermore, neither changes in chromatin condensation nor cell growth status
      were linked to these events. The inability of 3,4-dihydro-5-methylisoquinolinone
      (PD128763), a selective inhibitor of poly(ADP-ribose) polymerase, to impede
      insulin-dependent repression of PEPCK gene expression, however, indicated that 3
      aminobenzamide does not operate by inhibiting poly(ADP-ribosyl)ation. The
      potential involvement of mono(ADP-ribosyl)ation, a process that is also inhibited
      by 3-aminobenzamide, in the regulation of PEPCK gene activity was then evaluated.
      Analysis of poly(ADP-ribose) polymerase activity and poly(ADP-ribosyl)ation
      confirmed that there were no significant changes in response to insulin, while
      microsomal mono(ADP-ribosyl)transferase activity was elevated approximately
      fourfold. An increase in protein hydroxylamine-sensitive mono(ADP-ribosyl)ation
      was observed following insulin treatment. The sensitivity of the mono(ADP
      ribosyl)transferase activity to 3-aminobenzamide but not PD128763 makes it
      plausible that mono(ADP-ribosyl)ation rather than poly(ADP-ribosyl)ation
      contributes to the regulation of PEPCK gene expression.

PMID- 9578466
TI  - Cellobiose dehydrogenase enhances Phanerochaete chrysosporium cellobiohydrolase I
      activity by relieving product inhibition.
AB  - The interaction of cellobiose dehydrogenase (CDH) with cellobiohydrolase I (CBH
      I) in cellulose-grown cultures of Phanerochaete chrysosporium was investigated to
      clarify the role of CDH in cellulose degradation. Decomposition of bacterial
      microcrystalline cellulose by CBH I was enhanced significantly in the presence of
      the CDH/ferricyanide redox-system compared with CBH I alone. To explain this
      phenomenon, a model system, using p-nitrophenyl-beta-D-cellobioside as a
      substrate, was elaborated for measurement of CBH I activity with and without the
      CDH redox-system. The activity of CBH I for hydrolysis of p-nitrophenyl-beta-D
      cellobioside was also enhanced in the presence of the redox system. It was found
      that Km for hydrolysis of p-nitrophenyl-beta-D-cellobioside by CBH I was lower in
      the presence than in the absence of the CDH/ferricyanide redox-system, 142 microM
      and 384 microM, respectively, while no significant difference was observed
      between the k(cat) values. These results indicate that cellulase activity is
      enhanced by an increased affinity for p-nitrophenyl-beta-D-cellobioside, rather
      than by an increased hydrolysis rate. This shows that cellobiose, the hydrolysis
      product, acts as a competitive inhibitor of the interaction between CBH I and p
      nitrophenyl-beta-D-cellobioside. This was confirmed by addition of cellobiose,
      which was found to competitively inhibit hydrolysis of p-nitrophenyl-beta-D
      cellobioside by CBH I in the absence of the CDH redox system, and the Ki value
      for cellobiose inhibition was estimated to be 65 microM. However, this inhibition
      did not occur if cellobiose was incubated with CDH before addition of CBH I. It
      was concluded from these results that the reason for the enhancement of CBH I
      activity in the presence of the CDH redox system was that it relieves competitive
      inhibition of cellobiose by its oxidation to cellobionolactone.

PMID- 9578467
TI  - Cholesterol, but not its esters, triggers programmed cell death in human
      erythroleukemia K562 cells.
AB  - Cholesterol, its biosynthetic precursors and the cholesterol-lowering drug
      compactin were able to inhibit the growth of human erythroleukemia K562 cells.
      Compactin, farnesyldiphosphate and cholesterol were cytotoxic by the induction of
      apoptosis (programmed cell death, PCD). Compactin doubled the number of apoptotic
      cells compared to control numbers, whereas farnesyldiphosphate and cholesterol
      led to a fivefold increase in PCD over the control levels. At variance with
      cholesterol, cholesterol esters did not affect K562 cell viability and apoptotic
      body formation, regardless of chain length and degree of saturation. Compactin
      and farnesyldiphosphate reduced the membrane cholesterol content, thus increasing
      membrane fluidity. Conversely, cholesterol treatment reduced the membrane
      fluidity by increasing cholesterol content in the lipid bilayer. Unlike
      farnesyldiphosphate, the other cholesterol precursors and cholesterol esters were
      ineffective in increasing the cholesterol content and, thereby, the fluidity of
      cell membranes. Compactin and cholesterol precursors, apart from
      farnesyldiphosphate, did not affect the amount of the farnesylated proteins Ras
      and lamin B in the cytosolic and the membrane fractions of K562 cell extracts,
      whereas farnesyldiphosphate reduced the content of both proteins in both
      fractions. The level of lamin B in K562 cytosol and membranes was also reduced by
      cholesterol treatment, which did not significantly affect the amount of Ras.
      These findings highlight the role of cholesterol in promoting PCD.

PMID- 9578468
TI  - Delayed production of biologically active O-glycosylated forms of human eotaxin
      by tumor-necrosis-factor-alpha-stimulated dermal fibroblasts.
AB  - Since a number of inflammatory skin diseases are characterized by selective
      eosinophil infiltration preferentially in the dermis, we speculated that dermal
      fibroblasts might represent a potential cellular source of eosinophil-selective
      attractants. Cultivated dermal fibroblasts treated with tumor necrosis factor
      alpha secreted, not before day 3 of stimulation, eosinophil-specific chemotactic
      activity. Purification of this activity revealed a heparin-binding protein with
      an apparent molecular mass of 13 kDa in SDS/polyacrylamide gel electrophoresis.
      Peptide mapping with subsequent amino acid sequence analyses revealed it to be
      human eotaxin. Natural eotaxin preparations contain 50% N-terminally truncated
      forms missing two or three amino acids. It is O-glycosylated at Thr71, resulting
      in at least two sialylated O-glycosylated variants. Electrospray ionization mass
      spectrometric analyses revealed the natural eotaxin preparation to be
      heterogeneous with principal masses of 9033 Da and 9317 Da. Natural eotaxin
      stimulated eosinophil chemotaxis with identical potency and efficacy as
      recombinant human eotaxin. Neither neutrophils, monocytes or lymphocytes
      responded towards natural eotaxin preparations indicating that N-terminal
      truncation and O-glycosylation did not affect the cell-specificity of chemotactic
      activity. Treatment of eosinophils with natural eotaxin desensitizes chemotactic
      responses towards eotaxin, regulated an normal T-lymphocyte expressed and
      secreted (RANTES) and monocyte chemotactic protein 3 (MCP-3), whereas RANTES and
      MCP-3 were unable to desensitize natural eotaxin-dependent responses.

PMID- 9578469
TI  - Evidence that a peptide corresponding to the rat Muc2 C-terminus undergoes
      disulphide-mediated dimerization.
AB  - We have investigated the possibility that the intestinal mucin rat Muc2 forms
      dimers during biosynthesis via intermolecular disulphide bridging of its C
      terminal domains. Since the cysteine alignment of RMuc2 (and other secretory
      mucins) is similar to that of human von Willebrand factor, a similar C-tail to C
      tail dimerization may occur in mucins. The C-terminal domain of RMuc2 (534 amino
      acids) was expressed in COS-1 cells, and the products monitored by SDS/PAGE and
      western blotting with three antibodies to different regions of the C-terminal
      domain. In cells, the expressed domain was glycosylated and formed disulphide
      dependent dimers centred at approximately 150 kDa. The domain dimer, but not its
      precursor monomer, was secreted into the culture medium. The dimers in the media
      however, appeared to be 12-15-kDa heavier (i.e. had a slower mobility) than in
      cell lysates. Initial N-glycosylation, dimerization and secretion were inhibited
      by addition of tunicamycin to incubations, whereas benzyl-alpha-GalNAc did not
      interfere with these processes. However benzyl-alpha-GalNAc resulted in a
      decrease in the apparent size of secreted dimers, such that they now had the same
      mobility on gels as dimers normally seen in cell lysates (i.e. 150 kDa). A
      similar change in dimer size was observed after incubating untreated media
      samples with N-acetylneuraminidase. This suggests that benzyl-alpha-GalNAc caused
      inhibition of sialylation of cell dimers just before they were secreted. In
      summary, the C-terminal domain of RMuc2 can form disulphide-dependent dimers, and
      N-glycosylation is required for dimerization and subsequent secretion. A late
      sialylation event appears to precede the secretion of mucin domain dimers.

PMID- 9578470
TI  - A fully active FAD-containing precursor remains folded up to its translocation
      across the chloroplast membranes.
AB  - The cytosolic and two recombinant precursors, containing 10 and 30 amino acid
      spacers between the transit peptide and the mature region of the chloroplast
      flavoprotein ferredoxin-NADP+ reductase (FNR), were expressed in Escherichia coli
      cells. These proteins were purified rendering fully active precursors that
      contained bound FAD. Neither the transit peptide nor the spacers affected the
      formation of the tightly folded enzyme structure. Protease treatment of the
      folded precursors resulted in a rapid removal of the transit sequence, rendering
      an enzymatically active resistant core, even at high protease concentration. All
      three preproteins could be efficiently imported by isolated pea chloroplasts.
      Addition of the enzyme substrate NADP+ to the import medium slightly decreased
      the polypeptide translocation. The precursor bound to isolated chloroplasts in
      the presence or absence of leaf extracts was as resistant to proteolysis as the
      folded precursor in solution. In contrast, the FNR precursor unfolded by urea was
      rapidly digested even at the lowest protease concentration. Together, our results
      indicate that precursor unfolding may take place during translocation but not
      during binding to chloroplast envelopes or by interaction with leaf extract
      soluble factors, and that this process is independent of the distance between the
      transit peptide and the folded mature region of the protein.

PMID- 9578471
TI  - Ferric citrate uptake by cultured rat hepatocytes is inhibited in the presence of
      transferrin.
AB  - Diseases associated with iron overload occur worldwide. In subjects suffering
      from these conditions, transferrin is likely to be fully saturated and excess
      plasma iron must be complexed to other molecules. Consequently, the liver, which
      is the major site of iron storage, will be presented with iron in both
      transferrin-bound and non-transferrin-bound forms and these forms may compete for
      uptake by hepatocytes. The endogenous low-molecular-mass iron chelator, citrate,
      is considered to be a major contributing molecule to non-transferrin iron
      transport. This study was conducted to investigate the effects of transferrin on
      the uptake of citrate and iron citrate by hepatocytes in culture. Rat hepatocytes
      were incubated with 100 microM [14C]citrate and 1.0 microM 55Fe in the presence
      or absence of various forms of transferrin. Binding and internalisation of both
      citrate and iron were inhibited in a dose-dependent manner with increasing
      concentration of diferric transferrin, with iron uptake decreasing to less than
      5% of control values. Apotransferrin was markedly more effective in blocking
      citrate and iron uptake, reaching the same levels of inhibition at a 15-fold
      lower concentration of protein. The binding of citrate to the cell membrane was
      not affected significantly by changing the iron saturation of transferrin but
      internalisation decreased with decreasing saturation. In contrast, both the
      binding and internalisation of iron decreased with decreasing saturation.
      Incubations carried out using 55Fe-labelled citrate in the presence of 59Fe
      labelled diferric transferrin indicated that citrate-mediated iron binding by the
      cells decreased with increasing diferric transferrin concentrations but the
      citrate iron was not replaced by iron from transferrin during the 15-min
      incubation period. Instead, total iron uptake decreased. These data suggest that
      citrate-mediated iron uptake by hepatocytes shares at least one common pathway
      with transferrin-mediated iron uptake.

PMID- 9578472
TI  - Chemical modifications of the vasoconstrictor peptide angiotensin II by nitrogen
      oxides (NO, HNO2, HOONO)--evaluation by mass spectrometry.
AB  - Nitric oxide (NO) and angiotensin II are natural regulators of blood pressure.
      Under aerobic conditions, NO is transformed into its higher oxides (N2O4, NO2,
      NO/NO2 or N2O3) and oxoperoxonitrate (currently named peroxynitrite) by coupling
      with superoxide. Previous studies have shown that these reactive nitrogen species
      should be involved in vivo in the transformation of cysteine and tyrosine into
      the corresponding nitrosothiol and 3-nitrotyrosine. In the present study,
      attention has been focused on the relative reactivities of HNO2, peroxynitrite,
      and NO in the presence of dioxygen, towards the arginine and tyrosine residues of
      the peptide angiotensin II. Nitration of the tyrosine residue is clearly the main
      reaction with peroxynitrite. By contrast, besides 20% of nitration of the
      tyrosine residue, NO in the presence of dioxygen leads to nitrosation reactions
      with the arginine residue similar to those observed with HNO2 at pH 5, possibly
      through the intermediate N2O3 reactive species. Angiotensin II is converted for
      the most part to peptides having lost either a terminal amine function or the
      whole guanido group, leading respectively to citrulline-containing angiotensin II
      or to a diene derivative. Identification established mainly by tandem mass
      spectrometry of peptidic by-products allows us to propose a cascade of
      nitrosations of all the amine functions of the arginine residue. Further in vivo
      studies show that transformations of the arginine residue in angiotensin II do
      not alter its vasoconstrictive properties, whereas nitration of the tyrosine
      residue totally inhibits them.

PMID- 9578473
TI  - Processing of vertebrate box C/D small nucleolar RNAs in plant cells.
AB  - The recent isolation of a number of plant box C/D small nucleolar (sno)RNAs
      demonstrates the conservation in plants of sequence and structural elements of
      processed box C/D snoRNAs. Boxes C and D, and terminal inverted repeats are known
      to be essential for accumulation and processing in vertebrates and yeast.
      Processing of vertebrate box C/D snoRNAs was examined by expression of various
      mouse hsc70 intron 5-U14 constructs in tobacco protoplasts. Full-length U14 and
      internally deleted U14 accumulated in the plant cells. Human U3 and U8 fragments,
      consistent with processing to internal box C/C' sequences, also accumulated in
      the plant cells. The similarity of processing behaviour of the vertebrate box C/D
      constructs in tobacco protoplasts and Xenopus oocytes suggests the mechanism of
      processing, involving recognition and association of proteins, is conserved in
      plants.

PMID- 9578474
TI  - Chlorophyll alpha synthesis upon interruption and deletion of por coding for the
      light-dependent NADPH: protochlorophyllide oxidoreductase in a photosystem-I
      less/chlL- strain of Synechocystis sp. PCC 6803.
AB  - The gene coding for the light-dependent NADPH:protochlorophyllide oxidoreductase
      (POR) was interrupted or deleted in a Synechocystis sp. PCC 6803 strain lacking
      photosystem I (PS I) as well as ChlL, which takes part in light-independent
      catalysis of protochlorophyllide reduction. Interruption of por by a kanamycin
      resistance cartridge between the codons for M263 and V264 (about 83% into the
      coding region) did not abolish POR activity, but resulted in a decrease in the
      protochlorophyllide-(PChlide)-binding capacity of POR. Deletion of por in the PS
      I-less/chlL- strain generated a mutant [PS I-less/chlL-/por (del)] which
      accumulated both monovinyl-PChlide and divinyl-PChlide and excreted PChlides into
      the medium. This mutant also synthesized small amounts of protochlorophyllide
      dihydrogeranylgeraniol ester (protochlorophyll) when it was grown under light
      activated heterotrophic growth conditions. However, the mutant was still able to
      synthesize small amounts of normal chlorophyll a under weak continuous
      illumination, even though the quantum yield of chlorophyll a formation was
      reduced. Either protochlorophyll or PChlide reduction by an unspecific reductase
      or by a ChlB/ChlN complex could account for chlorophyll a synthesis in the PS I
      less/chlL-/por (del) strain. Functional photosystem II (PS II) was assembled in
      this mutant, but the PS II/chlorophyll ratio was fourfold lower than in the PS I
      less strain with normal chlorophyll synthesis. The PS I-less/chlL-/por (del)
      mutant had a 77-K fluorescence emission maximum at 685 nm but no peak or shoulder
      at 695 nm when the cells were excited at 435 nm. Much of the chlorophyll in the
      PS I-less/chlL-/por (del) mutant therefore seems to be associated with components
      other than PS II.

PMID- 9578475
TI  - Characterisation of a catabolic epoxide hydrolase from a Corynebacterium sp.
AB  - The epoxide hydrolase (EH) from Corynebacterium sp. C12, which grows on
      cyclohexene oxide as sole carbon source, has been purified to homogeneity in two
      steps, involving anion exchange followed by hydrophobic-interaction
      chromatography. The purified enzyme is multimeric (probably tetrameric) with a
      subunit size of 32,140 Da. The gene encoding Corynebacterium EH was located on a
      3.5-kb BamHI fragment of C12 chromosomal DNA using a DNA probe generated by PCR
      using degenerate primers based on the N-terminal and an internal amino acid
      sequence. Sequencing and database comparison of the predicted amino acid sequence
      of Corynebacterium EH shows that it is similar to mammalian and plant soluble EH,
      and the recently published sequence of epichlorohydrin EH from Agrobacterium
      radiobacter AD1 [Rink, R., Fennema, M., Smids, M., Dehmel, U. & Janssen, D. B.
      (1997) J. Biol. Chem. 272, 14650- 14657), particularly around the catalytic site.
      All of these proteins belong to the alpha/beta-hydrolase-fold family of enzymes.
      Similarity to the mammalian microsomal EH is weaker.

PMID- 9578476
TI  - Solution structures of the fibronectin-like Leishmania gp63 SRYD-containing
      sequence in the free and antibody-bound states--transferred NOE and molecular
      dynamics studies.
AB  - The anti-SRYD monoclonal antibody (mAbSRYD) raised against the IASRYDQL synthetic
      octapeptide, the 250-257 sequence of the Leishmania major surface glycoprotein
      gp63 recognizes both SRYD-containing peptides and the whole cognate major surface
      protein on intact parasites. Two SRYD-containing peptides, which antigenically
      and functionally mimic the RGDS sequence of fibronectin and efficiently inhibit
      parasite attachment to the macrophage receptors, were studied by two-dimensional
      transferred nuclear Overhauser effect experiments in the presence of mAbSRYD. The
      antibody-bound IASRYDQL octapeptide solution conformation was determined on the
      basis of 55 interproton-distance restraints, derived from NMR measurements.
      Eighteen structures which were first generated using an approach combining
      distance geometry and molecular dynamics, converge by energy minimization toward
      a folded structure with an average rmsd from the experimental data of less than
      0.05 nm for the overall backbone and 0.025 nm for the SRYD motif. A distorted
      gamma-turn was found, stabilized by the backbone-backbone D255-NH to R253-CO
      hydrogen bond, while the R253 and D255 side chains are pointing in opposite
      directions. This latter antibody-bound structure is compared with that of the
      free octapeptide in dimethylsulfoxide solution, and with the crystal structure of
      the RYD fragment in OPG2 Fab, an antireceptor antibody that mimics the RGD cell
      adhesion site. On this basis, a mechanism for IASRYDQL-receptor interaction is
      discussed.

PMID- 9578477
TI  - Lys42 and Ser42 variants of p-hydroxybenzoate hydroxylase from Pseudomonas
      fluorescens reveal that Arg42 is essential for NADPH binding.
AB  - The conserved Arg42 of the flavoprotein p-hydroxybenzoate hydroxylase is located
      at the entrance of the active site in a loop between helix H2 and sheet E1 of the
      FAD-binding domain. Replacement of Arg42 by Lys or Ser decreases the turnover
      rate of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens by more than
      two orders of magnitude. Rapid reaction kinetics show that the low activity of
      the Arg42 variants results from impaired binding of NADPH. In contrast to an
      earlier conclusion drawn for p-hydroxybenzoate hydroxylase from Acinetobacter
      calcoaceticus, substitution of Arg42 with Ser42 in the enzyme from P. fluorescens
      hardly disturbs the binding of FAD. Crystals of [Lys42]p-hydroxybenzoate
      hydroxylase complexed with 4-hydroxybenzoate diffract to 0.22-nm resolution. The
      structure of the Lys42 variant is virtually indistinguishable from the native
      enzyme with the flavin ring occupying the interior position within the active
      site. Lys42 in the mutant structure interacts indirectly via a solvent molecule
      with the 3-OH of the adenosine ribose moiety of FAD. Substrate perturbation
      difference spectra suggest that the Arg42 replacements influence the solvent
      accessibility of the flavin ring in the oxidized enzyme. In spite of this, the
      Arg42 variants fully couple enzyme reduction to substrate hydroxylation. Sequence
      comparison studies suggest that Arg42 is involved in binding of the 2'
      phosphoadenosine moiety of NADPH.

PMID- 9578478
TI  - Separation of horse dander allergen proteins by two-dimensional electrophoresis-
      molecular characterisation and identification of Equ c 2.0101 and Equ c 2.0102 as
      lipocalin proteins.
AB  - The aim of this work was to identify which proteins in horse dander extracts are
      allergens and to characterise them. Two-dimensional PAGE showed that horse dander
      preparations are composed of up to 50 proteins, all having acidic isoelectric
      points in the pH range 3-4.5. Immunoblots of two-dimensional PAGE were used to
      compare the reactivity of the proteins with IgE from 23 allergic patients.
      Patient sera were divided into two main groups recognising either allergens of
      18.5 kDa or proteins of 27-29 and 31 kDa. The proteins of 27-29 kDa and 31 kDa
      were all N-glycosylated and their glycan chains seem to play a role in the
      binding of IgE from allergic patients. The sugar composition of their
      carbohydrate moiety was determined and lectin-binding experiments indicated
      presence of terminal sialic acid linked alpha-(2-->6) to galactose, galactose
      linked beta-(1-->4) to N-acetylglucosamine, and possibly presence of sialic acid
      linked alpha-(2-->3) to galactose. The 27-29-kDa glycoproteins had heterogeneous
      isoelectric points, most probably due to different degrees of sialylation in
      their oligosaccharide chains. The two 18.5-kDa allergens exhibited slightly
      different isoelectric points and their N-terminal sequences were identical,
      showing that they most likely were isoforms of the same protein. Sequence
      analyses revealed that their N-terminal sequences are similar to proteins
      belonging to the lipocalin family. We named the two 18.5-kDa proteins Equ c
      2.0101 and Equ c 2.0102, according to International Allergen Nomenclature
      recommendations [King, T. P., Hoffman, D., Lowenstein, H., Marsh, D. G., Platts
      Mills, T. A. E. & Thomas, W. (1995) J. Allergy Clin. Immunol. 96, 5-14]. The N
      terminal of the allergens of 27-29 kDa were blocked and their sequences were not
      determined. Their amino acid compositions were determined and comparison with
      acidic mammalian proteins in the Swiss-Prot database revealed high scores with
      lipocalin proteins. This suggests that the glycosylated horse dander allergens
      belong to the lipocalin family, like Equ c 2.0101 and Equ c 2.0102.

PMID- 9578479
TI  - Bdellastasin, a serine protease inhibitor of the antistasin family from the
      medical leech (Hirudo medicinalis)--primary structure, expression in yeast, and
      characterisation of native and recombinant inhibitor.
AB  - We have reported earlier the isolation and amino acid composition of bdellin A
      from medical leech, and characterised it as an inhibitor of trypsin, plasmin and
      acrosin [Fritz, H., Gebhardt, M., Meister, R. & Fink, E. (1971) in Proceedings of
      the international research conference on proteinase inhibitors (Fritz, H. &
      Tschesche, H., eds) pp. 271-280, Walter de Gruyter, Berlin]. In the present
      study, one of several chromatographic forms of this inhibitor was isolated from a
      semi-pure preparation. Elucidation of its amino acid sequence revealed that
      bdellin A is a member of the antistasin family. Therefore, it was renamed
      bdellastasin to avoid confusion with bdellin B, which is another trypsin-plasmin
      inhibitor from the medical leech, but of the Kazal type. Furthermore, a synthetic
      gene of bdellastasin was constructed, and the protein expressed in Saccharomyces
      cerevisiae with yields of 29 mg/l. The recombinant bdellastasin was purified by
      hydrophobic interaction and anion-exchange chromatography. Comparison by mass
      spectroscopy, far-ultraviolet circular dichroism studies, sequence determination,
      and inhibition characteristics demonstrated the identity of recombinant and
      native bdellastasin. The Ki values of bdellastasin for inhibition of bovine
      trypsin and human plasmin are in the nanomolar range; no inhibition was detected
      for factor Xa, thrombin, tissue kallikrein, plasma kallikrein and chymotrypsin.
      Circular dichroism analyses indicated that bdellastasin is devoid of secondary
      structural elements.

PMID- 9578481
TI  - Labeling of Torpedo californica nicotinic acetylcholine receptor subunits by
      cobratoxin derivatives with photoactivatable groups of different chemical nature
      at Lys23.
AB  - Different photoactivatable derivatives of toxin 3 (CTX) Naja naja siamensis were
      obtained after CTX reaction with N-hydroxysuccinimide esters of p-azidobenzoic, p
      azidotetraflourobenzoic, p-benzoylbenzoic and p-[3-(trifluoromethyl)-3H-diazirin
      3-yl]benzoic acids. The ion-exchange HPLC profiles for the reaction products were
      very similar in four cases, with one predominant peak corresponding to the
      derivative containing the label at Lys23. After [125I]iodination, CTX
      photoactivatable derivatives were cross-linked to the nicotinic acetylcholine
      receptor from Torpedo californica under optimized conditions. The highest cross
      linking yield (up to 16% of the bound toxin) was observed for azidobenzoyl-Lys23
      CTX. Different receptor subunits were found to be labelled depending on the
      nature of the photoactivatable group: the azido derivatives labelled the gamma
      and delta subunits, benzoylbenzoyl derivative labelled the alpha and delta
      subunits, while p-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl derivative
      reacted with alpha, gamma and delta subunits. The cross-linking experiments in
      the presence of varying concentrations of (+)-tubocurarine demonstrated that the
      Lys23-attached diazirinyl group contacts the delta and alpha subunits in one
      ligand-binding site, whereas at the other site, for another CTX molecule, the
      contacts of the Lys23-diazirinyl are with gamma and alpha subunits. This means
      that the central loop in the two CTX molecules binds at the alpha/gamma and
      alpha/delta interfaces. Calculation of the sterically possible displacement of
      diazirinyl nitrogen, basing on the known X-ray structure of CTX, showed that this
      value does not exceed 13 A. The results obtained favor the disposition of the
      ligand-binding sites at the subunit interfaces, with the distance between alpha
      and delta, or alpha and gamma subunits at these sites being not more than 13 A.

PMID- 9578480
TI  - Solution structure of the antimicrobial peptide ranalexin and a study of its
      interaction with perdeuterated dodecylphosphocholine micelles.
AB  - Ranalexin, a 20-residue peptide isolated from the skin of the bullfrog Rana
      catesbeiana displays antimicrobial activity. This peptide contains two cysteine
      residues in positions 14 and 20 linked by a disulphide bridge. Ranalexin was
      chemically synthesised and close antimicrobial activities were measured for the
      reduced and oxidised forms. The solution structure of ranalexin was determined by
      using circular dichroism, proton NMR spectroscopy and molecular modelling
      techniques. The reduced and oxidised forms of ranalexin are mainly unstructured
      in water but display an alpha-helical structure spanning residues 8-15 and 8-17,
      respectively, in a trifluoroethanol/water mixture (3:7, by vol.). Ranalexin was
      found to interact with micelles of dodecylphosphocholine and to adopt a similar
      helical structure. Moreover, slow-exchanging amide protons located on the same
      side of the helix suggest that the hydrophobic face of the helix lies on the
      micelle surface. Hydrophobic residues of the poorly structured N-terminal part
      which are important for the biological activity are also involved in the
      interaction with micelles. Taken together, the results suggest that the
      disulphide bond does not strongly affect either the conformation or the
      antimicrobial activity of ranalexin.

PMID- 9578482
TI  - Helical and coiled-coil-forming properties of peptides derived from and
      inhibiting human immunodeficiency virus type 1 integrase assessed by 1H-NMR--use
      of NH temperature coefficients to probe coiled-coil structures.
AB  - Human immunodeficiency virus type 1 integrase (HIV-1 IN) which catalyzes viral
      DNA integration into the host genome of infected cells represents an attractive
      target for AIDS therapy. We have previously demonstrated the ability of the IN
      (147-175)-peptide derived from the catalytic core domain of HIV-1 IN to inhibit
      the enzyme activity in vitro. IN-(147-175)-peptide contains four heptad repeats
      and displays a high propensity for coiled-coil formation while its [P159]IN-(147
      175)-peptide analog (Lys159-->Pro in the protein, Lys13-->Pro in the peptide) is
      unable to form a stable coiled-coil and is devoid of inhibitory activity
      [Sourgen, F., Maroun, R. G., Frere, V., Bouziane, M., Auclair, C., Troalen, F. &
      Fermandjian, S. (1996) Eur. J. Biochem. 240, 765-773]. Now, we report results
      from an NMR study on IN-(147-175)-peptide and [P159]IN-(147- 175)-peptide as well
      as on an optimized [E156, A163, A167]IN-(147-175)-peptide that is a better
      inhibitor of IN than IN-(147-175)-peptide. While in aqueous solution, IN-(147
      175)-peptide and [P159]IN-(147-175)-peptide display only nascent helical
      features, [E156, A163, A167]IN-(147-175)-peptide exhibits 20% of helical content.
      In 20% trifluoroethanol/80% H2O, the helix content is the highest for [E156,
      A163, A167]IN-(147-175)-peptide (approximately 70%) and the lowest for [P159]IN
      (147-175)-peptide (approximately 40%), due to a local helix break caused by the
      Pro residue. The NHs of residues in the two central helical heptads (a-g) of IN
      (147-175)-peptide and [E156, A163, A167]IN-(147-175)-peptide display a regular
      periodic variation of their temperature coefficients in 20% trifluoroethanol. The
      b, c and f residues on the hydrophilic face of the amphipathic helix show high
      coefficients reflecting hydrogen bonded NHs, while the a and d residues on the
      hydrophobic face exhibit low coefficients, near random-coil values. The
      particular arrangement of the hydrophobic side-chains of a and d residues at the
      coiled-coil interface reduces the access of trifluoroethanol molecules to their
      amide groups. The inability of trifluoroethanol molecules to create interactions
      with the amide C=O groups, these being required to strengthen the intrahelical
      C=O...H-N hydrogen bonds, is the main cause for observation of heptadic a and d
      residues with low NH temperature coefficients. Such effects concern mostly the
      two central helical heptads of IN-(147-175)-peptide and [E156, A163, A167]IN-(147
      175)-peptide implying that these ones are engaged in stable parallel coiled
      coils. Our results provide a link between the propensity of peptides for helix
      formation, their coiled-coil properties and their efficiency to inhibit IN.

PMID- 9578483
TI  - Binding of the Co(NH3)4 derivative of (2')3'-O-[N-methyl-anthraniloyl]-ATP to the
      E2ATP site of Na+/K+-transporting ATPase lowers the conformational flexibility of
      its E1ATP site.
AB  - Na+/K+-activated ATP hydrolysis by the sodium pump is catalyzed by the
      interaction of high-affinity and low-affinity ATP-binding sites [Thoenges, D. &
      Schoner, W. (1997) J. Biol. Chem. 272, 16315-16321]. To explore how binding of
      ATP to the low-affinity E2ATP site affects the conformational flexibility of the
      high-affinity E1ATP site due to interaction with Na+ or K+ ions, the E2ATP site
      was blocked with a fluorescent MgATP complex analog and fluorescence changes of
      the E1ATP site modified by FITC (fluorescein 5'-isothiocyanate) were studied. The
      fluorescent MgATP complex analog Co(NH3)4MANT-ATP [beta,gamma-bidentate complex
      of 2'(3')-O-(N-methylanthraniloyl)-ATP] inactivated Na+/K+-ATPase in a time
      dependent and concentration-dependent process with a Kd of 0.17 mM and an
      inactivation rate constant, k, of 0.031 min(-1). ATP protected against the
      inactivation with a Kd of 0.43 mM. Consistent with a modification of the E2ATP
      binding site, Co(NH3)4MANT-ATP inactivated the K+-activated phosphatase activity
      in an enzyme whose E1ATP site had already been modified by FITC. Inactivation by
      Co(NH3)4MANT-ATP was due to tight binding which resulted in a loss of
      fluorescence. Tightly bound Co(NH3)4MANT-ATP could only be released by
      denaturation with SDS. Analysis of the conformational flexibility of the E1ATP
      site after labeling with FITC led to a K+-dependent quench of fluorescence which
      is reversed by Na+. This flexibility was lost upon the blockade of the E2ATP site
      by Co(NH3)4MANT-ATP.

PMID- 9578484
TI  - Molecular and enzymatic characterization of a maltogenic amylase that hydrolyzes
      and transglycosylates acarbose.
AB  - A gene encoding a maltogenic amylase of Bacillus stearothermophilus ET1 was
      cloned and expressed in Escherichia coli. DNA sequence analysis indicated that
      the gene could encode a 69,627-Da protein containing 590 amino acids. The
      predicted amino acid sequence of the enzyme shared 47-70% identity with the
      sequences of maltogenic amylase from Bacillus licheniformis, neopullulanase from
      B. stearothermophilus, and cyclodextrin hydrolase (CDase) 1-5 from an
      alkalophilic Bacillus 1-5 strain. In addition to starch, pullulan and
      cyclodextrin, B. stearothermophilus could hydrolyze isopanose, but not panose, to
      glucose and maltose. Maltogenic amylase hydrolyzed acarbose, a competitive
      inhibitor of amylases, to glucose and a trisaccharide. When acarbose was
      incubated with 10% glucose, isoacarbose, containing an alpha-1,6-glucosidic
      linkage was produced as an acceptor reaction product. B. stearothermophilus
      maltogenic amylase shared four highly similar regions of amino acids with several
      amylolytic enzymes. The beta-cyclodextrin-hydrolyzing activity of maltogenic
      amylase was enhanced to a level equivalent to the activity of CDase when its
      amino acid sequence between the third and the fourth conserved regions was made
      more hydrophobic by site-directed mutagenesis. Enhanced transglycosylation
      activity was observed in most of the mutants. This result suggested that the
      members of a subfamily of amylolytic enzymes, including maltogenic amylase and
      CDase, could share similar substrate specificities, enzymatic mechanisms and
      structure/function relationships.

PMID- 9578485
TI  - The function of the periplasmic Sud protein in polysulfide respiration of
      Wolinella succinogenes.
AB  - The periplasmic Sud protein was previously isolated as a sulfide dehydrogenase
      from Wolinella succinogenes. Sud modified by a C-terminal His-tag (Sud-His6) was
      produced in Escherichia coli by expression of the sud gene. Sud-His6 catalyzed
      thiocyanate formation from cyanide and polysulfide. The Vmax of this activity was
      more than one order of magnitude higher than that of sulfide oxidation by
      dimethyl-naphthoquinone and that of polysulfide reduction by BH4-. The apparent
      Km was less than 20 microM polysulfide. Polysulfide and not elemental sulfur was
      found to be the product of sulfide oxidation by dimethyl-naphthoquinone, in
      contrast to the earlier view [Kreis-Kleinschmidt, V., Fahrenholz, F., Kojro, E. &
      Kroger. A. (1995) Arch. Microbiol. 165, 65-68]. Sud-His6 did not contain metal
      ions or other prosthetic groups. Replacement by site-directed mutagenesis of the
      single cysteine residue of the Sud monomer caused complete loss of activity,
      while the exchange of the single histidine residue or of the lysine residue
      situated next to cysteine did not affect activity. In equilibrium dialysis, the
      Sud-His6 monomer bound up to ten polysulfide sulfur atoms with a dissociation
      constant of 0.2 mM. Sud-His6 loaded with polysulfide sulfur showed an absorption
      spectrum in the range of 350-400 nm; this spectrum differed from that of free
      polysulfide. Electron transport from H2 to polysulfide catalyzed by the membrane
      fraction of W. succinogenes was stimulated by the presence of small amounts of
      Sud-His6. The apparent Km for polysulfide decreased sevenfold in the presence of
      saturating amounts of Sud-His6 (1 microM Sud-His6 dimer). Similar results were
      obtained with intact W. succinogenes cells containing low and high amounts of
      Sud. Sud appears to function as a polysulfide binding protein and probably binds
      polysulfide sulfur to its cysteine residue and transfers it to the substrate site
      of the membraneous polysulfide reductase.

PMID- 9578486
TI  - Isolation and characterization of an evolutionary precursor of human monoamine
      oxidases A and B.
AB  - An interesting flavoprotein-type monoamine oxidase (MAO) was recently isolated
      from Aspergillus niger and cloned [Schilling, B. & Lerch, K. (1995a) Biochim.
      Biophys. Acta 1243, 529-537; Schilling, B. & Lerch, K. (1995b) Mol. Gen. Genet.
      247, 430-438]. The properties of this MAO, as well as a substantial part of its
      amino acid sequence, resemble those of both MAO A and B from higher animals,
      raising the possibility that it may be an evolutionary precursor of these
      mitochondrial enzymes. It differs from MAO A and B in several respects, however,
      including the fact that it is soluble and of peroxisomal location and that the
      FAD is non-covalently attached. We have overexpressed the fungal enzyme (MAO-N)
      in Escherichia coli and isolated it in pure form. Since several of the
      observations of previous workers on MAO-N could not be reproduced, we have
      reexamined its substrate specificity, interaction with reversible and
      irreversible inhibitors and other catalytic and molecular properties. MAO-N has a
      considerably higher turnover number on many aliphatic and aromatic amines than
      either form of the mammalian enzyme. Some aspects of the substrate specificity
      resemble those of MAO B, while others are similar to MAO A, including biphasic
      kinetics in double reciprocal plots. Contrary to a previous report [Schilling, B.
      & Lerch, K. (1995a) Biochim. Biophys. Acta 1243, 529-537], however, the fungal
      enzyme does not oxidize serotonin, norepinephrine, dopamine or other biogenic
      amines. MAO-N is irreversibly inhibited by stoichiometric amounts of both (
      )deprenyl and clorgyline in a mechanism-based reaction, forming flavocyanine
      adducts with N5 of the FAD, like the mammalian enzymes, but inactivation is much
      faster with clorgyline than deprenyl, suggesting a closer resemblance to MAO A
      than B. The dissociation constants for a large number of reversible competitive
      inhibitors have been determined for MAO-N and comparison with similar values for
      MAO A and B again pointed to a greater similarity to the former than the latter.

PMID- 9578487
TI  - Carbamate kinase from Enterococcus faecalis and Enterococcus faecium--cloning of
      the genes, studies on the enzyme expressed in Escherichia coli, and sequence
      similarity with N-acetyl-L-glutamate kinase.
AB  - Carbamate kinase (CK) catalyzes the reversible reaction NH2COO- + ATP <-->
      NHCOOPO3(2-) + ADP, serving to synthesize ATP from carbamoyl phosphate in those
      microorganisms that derive energy from anaerobic arginine degradation via the
      arginine dihydrolase pathway. We report here the cloning and sequencing of the CK
      gene from Enterococcus faecalis and Enterococcus faecium and we demonstrate that
      the amino acid sequence of CK is identical in the two species. The enzyme,
      expressed and isolated from Escherichia coli using simple purification
      procedures, was used to generate crystals suitable for X-ray studies and to
      investigate the utilization by CK of bicarbonate and other carbamate analogs. CK
      had a bicarbonate-dependent ATPase activity and, therefore, is able to synthesize
      carboxyphosphate, an unstable compound that is an intermediate in the reactions
      catalyzed by carbamoyl-phosphate synthetase (CPS) and by biotin carboxylase.
      Other functional similarities with CPS include the utilization of acetate by CK
      with a similarly high Km and the similar Km values of CK for carbamate and of CPS
      for bicarbonate. Enterococcal CK was inhibited by
      adenosine(5')pentaphospho(5')adenosine (Ap5A) and Ap6A and, less powerfully, by
      Ap4A, whereas Ap3A is essentially non-inhibitory. Thus, inhibition by Ap5A seems
      not to be a valid criterion to differentiate between CK and CPS, for the two
      enzymes can be inhibited by Ap5A. All these results support the relatedness of CK
      and CPS. Finally, we used limited proteolysis: (a) to localize the epitopes for
      monoclonal antibodies obtained against CK; (b) to demonstrate the importance of
      the C-terminus for enzyme activity; and (c) to show that Arg158 is highly exposed
      and may be essential for activity. Comparison of the sequence of CK with known
      protein sequences demonstrates considerable similarity of CK with bacterial N
      acetylglutamate kinases, strongly suggesting that these two enzymes may share a
      similar structure and the same catalytic mechanism.

PMID- 9578488
TI  - Thiol:fumarate reductase (Tfr) from Methanobacterium thermoautotrophicum-
      identification of the catalytic sites for fumarate reduction and thiol oxidation.
AB  - Most methanogenic Archaea contain an unusual cytoplasmic fumarate reductase which
      catalyzes the reduction of fumarate with coenzyme M (CoM-S-H) and coenzyme B (CoB
      S-H) as electron donors forming succinate and CoM-S-S-CoB as products. We report
      here on the purification and characterization of this thiol:fumarate reductase
      (Tfr) from Methanobacterium thermoautotrophicum (strain Marburg). The purified
      enzyme, which was composed of two different subunits with apparent molecular
      masses of 58 kDa (TfrA) and 50 kDa (TfrB), was found to catalyze the following
      reactions: (a) the reduction of fumarate with CoM-S-H and CoB-S-H (150 U/mg); (b)
      the reduction of fumarate with reduced benzyl viologen (620 U/mg); (c) the
      oxidation of CoM-S-H and CoB-S-H to CoM-S-S-CoB with methylene blue (95 U/mg);
      and (d) the reduction of CoM-S-S-CoB with reduced benzyl viologen (250 U/mg). The
      flavoprotein contained 12 mol non-heme iron and approximately the same amount of
      acid-labile sulfur/mol heterodimer. The genes encoding TfrA and TfrB were cloned
      and sequenced. Sequence comparisons with fumarate reductases and succinate
      dehydrogenases from Bacteria and Eucarya and with heterodisulfide reductases from
      M. thermoautotrophicum and Methanosarcina barkeri revealed that TfrA harbors FAD
      binding motifs and the catalytic site for fumarate reduction and that TfrB
      harbors one [2Fe-2S] cluster and two [4Fe-4S] clusters and the catalytic site for
      CoM-S-H and CoB-S-H oxidation.

PMID- 9578489
TI  - The conversion of recombinant human mast cell prochymase to enzymatically active
      chymase by dipeptidyl peptidase I is inhibited by heparin and histamine.
AB  - Chymase, a major product of mast cell activation, is secreted as a fully active
      enzyme. We have prepared recombinant human prochymase and have investigated the
      conditions under which it may be activated by dipeptidyl peptidase I (DPP I). The
      gene for human chymase was cloned in a baculovirus vector and expressed in High
      Five insect cells, and the recombinant protein purified by heparin-agarose and
      gel-filtration chromatography. The purified prochymase was homogeneous by
      SDS/PAGE with the same molecular mass as native human chymase, and its identity
      confirmed by N-terminal sequence analysis and Western blotting with chymase
      specific antibodies. Treatment with DPP I to remove the N-terminal dipeptide
      prosequence resulted in enzymatically active chymase, with substrate and
      inhibitor profiles very similar to those of the native human enzyme. The
      activation of prochymase by DPP I was strongly inhibited by heparin (IC50 = 0.5
      microg ml[-1]) and histamine (IC50 = 2 mM), though these mast cell products had
      little effect on the action of DPP I towards a low molecular-mass substrate. The
      pH optimum of DPP I was also higher and narrower with prochymase. The inhibitory
      action of heparin was lost at NaCl or KCl concentrations sufficient to elute
      prochymase from a heparin agarose column. Dextran sulphate was as inhibitory as
      heparin, whereas chondroitin sulphate C was more than 10-fold less effective. Our
      findings suggest that the activation of prochymase might be restricted to the
      early stages of vesicle maturation, when the pH is close to neutrality and the
      histamine and heparin concentrations are low.

PMID- 9578490
TI  - Role of sialosyl Lewis(a) in adhesion of colon cancer cells--the antisense RNA
      approach.
AB  - To study whether the adhesion of colon cancer cells to E-selectin can be directly
      affected by changes in the expression level of sialosyl Le(a) antigen we created
      a specific loss-of-function phenotype. A stable subclone (CX-1.1) with high
      expression of sialosyl Le(a) structure, obtained from a heterogenous population
      of colon carcinoma CX-1 cells, was transfected with an expression vector
      containing a fragment of cDNA for alpha1,3/4-fucosyltransferase in antisense
      orientation. After transfection, the cell line was isolated which did not express
      sialosyl Le(a) antigen and lacked the alpha1,3/4-fucosyltransferase activity,
      despite an unchanged level of mRNA specific for this enzyme. It was found that
      the specific lack of expression of sialosyl Le(a) carbohydrate structure on the
      surface of colon cancer cells completely abolished their adhesion to E-selectin.
      To evaluate which cellular glycoconjugates carry sialosyl Le(a) antigen,
      glycoproteins as well as glycolipids of CX-1.1 cells were analysed for the
      expression of this structure. Anti-sialosyl Le(a) antibodies detected multiple
      glycoprotein bands with apparent molecular masses of 65-280 kDa on western blots,
      and an intense band representing sialosyl Le(a)-ganglioside on a thin-layer
      chromatogram. Using O-sialoglycoprotease from Pasteurella haemolytica and an
      alkaline beta-elimination procedure, it was shown that protein-linked sialosyl
      Le(a) structures are carried mostly by mucin-type glycoproteins. However,
      treatment of CX-1.1 cells with O-sialoglycoprotease did not decrease either their
      binding to E-selectin-expressing Chinese hamster ovary cells, or binding of anti
      sialosyl Le(a) antibodies to the cell surface. These results suggested that
      cleavage of sialomucins uncovered cryptic sialosyl Le(a)-ganglioside, which was
      inaccessible for the antibody and E-selectin in untreated cells. This hypothesis
      was confirmed to some extent by the higher accessibility of gangliosides to
      galactose oxidase on the surface of O-sialoglycoprotease-treated CX-1.1 cells,
      comparing to untreated cells. We propose that glycoproteins as well as
      gangliosides carrying sialosyl Le(a) structures, when properly exposed and
      present in high density on surface of cancer cells, can effectively support the
      adhesion of cancer cells to E-selectin.

PMID- 9578491
TI  - Structural characterization of the lipopolysaccharide O-antigen and capsular
      polysaccharide of Vibrio ordalii serotype O:2.
AB  - Structures of the capsular and O-chain polysaccharides of Vibrio ordalii serotype
      O:2, the causative agent of vibriosis in salmonid fish, were determined by high
      field NMR techniques, mass spectrometric methods and partial hydrolysis. Both
      polymers were shown to be composed of linear tetrasaccharide repeating units,
      having the structure: carbohydrate sequence [see text].

PMID- 9578492
TI  - The C-terminal helix of human apolipoprotein AII promotes the fusion of
      unilamellar liposomes and displaces apolipoprotein AI from high-density
      lipoproteins.
AB  - To assess the functional properties of apolipoprotein (apo) AII and to
      investigate the mechanism leading to the displacement of apo AI from native and
      reconstituted high-density lipoproteins (HDL and r-HDL) by apo AII, wild-type and
      variant apo AII peptides were synthesized. The wild-type peptides, residues 53-70
      and 58-70, correspond to the C-terminal helix of apo AII and are predicted to
      insert at a tilted angle into a lipid bilayer. We demonstrate that both the apo
      AII-(53-70) peptide, and to a lesser extent the apo AII-(58-70) peptide are able
      to induce fusion of unilamellar lipid vesicles together with membrane leakage,
      and to displace apo AI from HDL and r-HDL. Two variants of the apo AII-(53-70)
      wild-type (WT) peptide, designed either to be parallel to the water/lipid
      interface [apo AII-(53-70)-0 degrees] or to retain an oblique orientation [apo
      AII-(53-70)-30 degrees], were synthesized in order to test the influence of the
      obliquity on their fusogenic properties and ability to displace apo AI from HDL.
      The parallel variant did not bind lipids, due to its self-association properties.
      However, the apo AII-(53-70)-30 degrees variant was fusogenic and promoted the
      displacement of apo AI from HDL. Moreover, the extent of fusion of the apo AII
      (53-70)-WT, apo AII-(58-70)-WT and apo AII-(53-70)-30 degrees peptides was
      related to the alpha-helical content of the lipid-bound peptides measured by
      infrared spectroscopy. Infrared measurements using polarized light also confirmed
      the oblique orientation of the helical component of the three peptides. In native
      and r-HDL, the tilted insertion of the C-terminal helix of apo AII resulting in a
      partial destabilization of the HDL external lipid layer might contribute to the
      displacement of apo AI by apo AII.

PMID- 9578493
TI  - Location of N-cyclohexyl-N'-(4-dimethyl-amino-alpha-naphthyl)carbodiimide-
      binding site in sarcoplasmic reticulum Ca2+-transporting ATPase.
AB  - The Ca2+-transporting ATPase has been labeled with N-cyclohexyl-N'-(4-dimethyl
      amino-alpha-naphthyl)carbodiimide (NCD-4), a fluorescent carbodiimide which
      reacts with carboxyl groups of acidic residues. It has been reported that NCD-4
      labels a transmembrane portion of the protein at the high-affinity calcium
      binding sites. We have determined the depth of the calcium-sensitive probe by
      quenching the fluorescence by nitroxide-substituted fatty acids with its spin
      probe located at different carbons of the fatty acid chain (5, 7, 10, 12 and 16
      nitroxide derivatives). We have found that all the calcium-sensitive fluorescence
      is quenched and that the efficiency of quenching decreases as the n-(4,4-dimethyl
      3-oxazolinyloxy) (Doxyl) group is deeper in the membrane. We conclude that the
      NCD-4 label which is involved in the high-affinity calcium-binding site is
      located near the water/lipid interface. The fluorescence of the NCD-4 bound to
      that site can be quenched by acrylamide and Cu2+ but not by iodide, probably due
      to its anionic nature which will be repulsed by the abundance of negative charges
      of Glu and Asp residues of NCD-4 located at this site. The hydrophobic location
      of NCD-4 was confirmed by the fact that its fluorescence could be quenched by the
      spin label 2,2,6,6-tetramethyl-1-piperidine-N-oxyl but not by 4-hydroxy-2,2,6,6
      tetramethyl-1-piperidine-N-oxyl which is much less hydrophobic.

PMID- 9578494
TI  - Involvement of calcium and arachidonate metabolism in acetylated-low-density
      lipoprotein-stimulated tumor-necrosis-factor-alpha production by rat peritoneal
      macrophages.
AB  - We show that lipopolysaccharide-free actetylated low-density lipoprotein (LDL),
      but not native LDL, stimulates tumor-necrosis factor-alpha (TNF-alpha) secretion
      by rat peritoneal macrophages and the signal-transduction pathways involved. The
      role of the scavenger receptor (SR) in this response was suggested by the absence
      of an effect induced by native LDL, signal coupling involving pertussis-toxin
      dependent guanine-nucleotide-binding regulatory (G) protein, and the complete
      inhibition of this response by SR ligands [poly(I) and dextran sulfate].
      Acetylated LDL induces rapid Ca2+ release from inositol-phosphate-sensitive Ca2+
      stores mediated by pertussis-sensitive G proteins and a sustained Ca2+ rise
      mediated by Ca2+ influx and by Ca2+ release from ryanodine-sensitive Ca2+ stores.
      Acetylated LDL-induced Ca2+ influx and TNF-alpha production were abolished by
      inhibitors of phospholipase C (U73122) and phospholipase A2 (bromophenacyl
      bromide), but were not affected by an inhibitor of protein kinase C (calphostine
      C). Therefore, Ca2+ influx induced by acetylated LDL is dependent on Ca2+ store
      depletion. Arachidonate released by acetylated LDL acts as a second messenger to
      activate TNF-alpha secretion via Ca2+ influx. While the Ca2+ signal was not
      modified by an inhibitor of protein tyrosine kinases (PTK; herbimycin A), this
      inhibitor completely blocked TNF-alpha production, suggesting the involvement of
      PTK downstream of the Ca2+ signal. These results suggest that a sustained
      elevation of intracellular Ca2+, mediated through Ca2+ influx via the
      phospholipase-A2-dependent pathway, is essential for induction of TNF-alpha
      secretion. The type of SR class involved in these pathways remains to be
      identified.

PMID- 9578495
TI  - Partially deglycosylated human choriogonadotropin, stabilized by intersubunit
      disulfide bonds, shows full bioactivity.
AB  - Several studies indicate that in human choriogonadotropin the N-linked
      oligosaccharide at position 52 of the alpha-subunit is important for bioactivity.
      We have generated choriogonadotropin mutants in which the alpha52 glycosylation
      site is removed and the alpha and beta subunits are covalently linked by
      intersubunit disulfide bonds. These mutants display wild-type receptor binding
      and bioactivity. Furthermore, we show that removal of the alpha52 sugar leads to
      instability of heterodimeric choriogonadotropin. Therefore, we conclude that the
      alpha52 oligosaccharide of choriogonadotropin is not involved in signal
      transduction, but in the stability of the heterodimer.

PMID- 9578496
TI  - Activating mutations of the thyrotropin receptor: a short review with emphasis on
      some pediatric aspects.

PMID- 9578497
TI  - Orderliness of hormone release patterns: a complementary measure to conventional
      pulsatile and circadian analyses.

PMID- 9578499
TI  - Effects of smoking on thyroid function.

PMID- 9578498
TI  - Regulation of catecholamine synthesizing enzyme gene expression in human
      pheochromocytoma.

PMID- 9578500
TI  - Crucial role for type II iodothyronine deiodinase in the metabolic coupling
      between glial cells and neurons during brain development.

PMID- 9578501
TI  - Vitamin D receptor knock-out mice: the expectational and the exceptional.

PMID- 9578502
TI  - The sodium iodide symporter: its emerging relevance to clinical thyroidology.

PMID- 9578503
TI  - Effect of passive smoking on thyroid function in infants.
AB  - OBJECTIVE: To evaluate the effect of passive smoking on thyroid function in
      infants. DESIGN AND METHODS: Cord serum tri-iodiothyronine (T3), free T3 (fT3),
      thyroxine (T4), free T4 (fT4), TSH, thyroxine binding globulin (TBG),
      thyroglobulin (TG) and cord plasma thiocyanate were measured at birth, and serum
      TG and thiocyanate after 1 year of life, in 18 infants born from parents who did
      not smoke (group A), in 18 infants with a father who smoked (group B) and in 18
      infants with parents both being smokers (group C). RESULTS: No significant
      differences were observed in cord serum concentrations of T3, fT3, T4, fT4, TSH
      and TBG among the three groups. Median (range) TG concentrations (ng/ml) were
      30.2 (5.0-102.0), 56.3 (20.5-208.0) and 76.0 (26.0-199.0) at birth (P=0.009 for
      groups A and B compared; P=0.0002 for groups A and C compared), and 14.9 (5.4
      32.0), 19.5 (10.0-57.5) and 20.0 (14.0-40.7) at 1 year (P=0.017 for groups A and
      C compared), in the three groups respectively, and thiocyanate concentrations
      (mmol/l) were 3.3 (0.0-51.4), 12.9 (0.0-122.2) and 27.8 (3.3-184.5) at birth
      (P=0.015 for groups A and C compared), and 3.1 (0.0-32.7), 6.0 (0.0-47.3) and
      20.3 (0.0-230.8) at 1 year (P=0.01 for groups A and C compared) in the three
      groups respectively. CONCLUSIONS: TG and thiocyanate concentrations at birth and
      at 1 year of age in infants of smoking parents are greater than in infants with
      non-smoking parents. These results indicate that the change in thyroid function
      as evaluated by serum TG concentrations observed at birth can persist at least
      for 1 year if the exposure to passive smoking from both parents is continued.
      Increased TG concentrations may be due to a direct effect of thiocyanate on the
      thyroid gland.

PMID- 9578504
TI  - Expression of mRNA coding for four catecholamine-synthesizing enzymes in human
      adrenal pheochromocytomas.
AB  - OBJECTIVE: To understand the molecular mechanisms by which catecholamine
      synthesis is controlled in pheochromocytomas--tumors that synthesize and release
      catecholamines, which are related to various clinical manifestations of the
      condition. METHODS: We measured the concentrations of mRNA coding for the
      catecholamine-synthesizing enzymes tyrosine hydroxylase, aromatic L-amino acid
      decarboxylase (AADC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N
      methyl transferase (PNMT) and for the catecholamine contents in 12
      pheochromocytomas and 12 normal adrenal medullas. RESULTS: The mean content of
      total catecholamine and the beta-actin mRNA expression in the pheochromocytomas
      were almost the same as those in the normal adrenal medullas. However, the
      tyrosine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocytomas
      were greater than those of the normal adrenal medullas. Conversely, the PNMT mRNA
      concentration in the pheochromocytomas was lower than that in the normal adrenal
      medullas. These differences are responsible for the difference in the proportions
      of catecholamines between pheochromocytomas and normal adrenal medullas. The
      constitutive expression of the catecholamine-synthesizing enzyme mRNAs varied in
      magnitude among the pheochromocytomas, and the tyrosine hydroxylase mRNA
      expressions correlated with the contents of total catecholamine in the tumors
      (r=0.964, P<0.0001). CONCLUSIONS: These findings indicate that catecholamine
      production in pheochromocytomas is primarily controlled by the level of gene
      expression.

PMID- 9578505
TI  - Increased plasma concentration of epidermal growth factor in female patients with
      non-toxic nodular goitre.
AB  - OBJECTIVE: Epidermal growth factor (EGF) is believed to be one of the most potent
      growth factors for the thyroid gland. DESIGN AND METHODS: We tested plasma EGF
      concentrations (radioreceptor method) in patients with non-toxic nodular goitre
      (NNG). Blood samples from patients with NNG were collected on the day before the
      surgery, during subtotal thyroidectomy (sTx)--from peripheral and thyroid veins,
      on the 3rd day after sTx, 3 months after sTx, and 9 months after the surgery.
      RESULTS: Before the operation, the mean plasma EGF concentration in 50 women with
      NNG was significantly higher (1.16 +/- 0.69 ng/ml; mean +/- S.E.) than that in 32
      control female patients subjected subsequently to other (non-thyroid) operations
      (0.41 +/- 0.27 ng/ml; P < 0.001), and that in 20 healthy women (0.35 +/- 0.11
      ng/ml; P < 0.001), both of which groups were without goitre or had a small non
      toxic diffuse goitre. The surgical treatment of NNG resulted in a significant
      reduction in plasma EGF 3 months after sTx (0.56 +/- 0.22 ng/ml). A further
      slight decrease was observed 9 months after sTx (0.44 +/- 0.14 ng/ml).
      CONCLUSIONS: Our observations confirm the assumption that EGF may participate in
      the process of goitre formation in human subjects. However, the source of EGF
      involved in this process remains unclear. Some findings could suggest that plasma
      EGF, which was increased in patients with NNG, may be of non-thyroid origin;
      however, the majority of our observations strongly stress the significance of an
      intact thyroid in the preservation of an unchanged EGF value, suggesting a role
      of locally produced EGF in the pathogenesis of NNG.

PMID- 9578506
TI  - GH response to provocation and circulating IGF-I and IGF-binding protein-3
      concentrations, the IGF-I generation test and clinical response to GH therapy in
      children with beta-thalassaemia.
AB  - The causes of growth retardation of children with thalassaemia major are
      multifactorial. We studied the GH response to provocation by clonidine and
      glucagon, measured the circulating concentrations of insulin, IGF-I, IGF-binding
      protein-3 (IGFBP-3) and ferritin, and evaluated IGF-I generation after a single
      dose of GH (0.1 mg/kg per dose) in 15 prepubertal patients with thalassaemia, 15
      age-matched children with constitutional short stature (CSS) (height standard
      deviation score less than -2, with normal GH response to provocation) and 11
      children with isolated GH deficiency (GHD). Children with thalassaemia had
      significantly lower peak GH response to provocation by clonidine and glucagon
      (6.2 +/- 2.3 and 6.8 +/- 2.1 microg/l respectively) than the CSS group (18.6 +/-
      2.7 and 16.7 +/- 3.7 microg/l respectively). They had significantly decreased
      circulating concentrations of IGF-I and IGFBP-3 (47.5 +/- 19 ng/ml and 1.2 +/-
      0.27 mg/l respectively) compared with those with CSS (153 +/- 42 ng/ml and 2.06
      +/- 0.37 mg/l respectively), but the IGF-I and IGFBP-3 concentrations were not
      different from those with GHD (56 +/- 25 ng/ml and 1.1 +/- 0.32 mg/l
      respectively). These data demonstrate that the GH-IGF-I-IGFBP-3 axis in
      thalassaemic children is defective. Serum ferritin concentration correlated
      significantly with GH peak response to provocation (r = -0.36, P < 0.05) and
      circulating IGF-I (r = -0.47, P < 0.01) and IGFBP-3 (r = -0.42, P < 0.01)
      concentrations. In the IGF-I generation test, after GH injection, the
      thalassaemic children had significantly lower IGF-I and IGFBP-3 levels 86.7 +/-
      11.2 ng/ml and 2.05 +/- 0.51 mg/l respectively) than those in the CSS group (226
      +/- 45.4 ng/ml and 2.8 +/- 0.43 mg/l respectively). The IGF-I response was
      significantly higher in children with GHD (158 +/- 50 ng/ml) than in thalassaemic
      children. Six short (height standard deviation score less than -2) thalassaemic
      children who had defective GH response to provocation (< 10 microg/l), all the
      children with GHD and eight short normal children (CSS) were treated for 1 year
      with human GH (18 units/m2 per week divided into daily s.c. doses). After 1 year
      of GH therapy there was a marked acceleration of growth velocity in both
      thalassaemic children (from 3.8 +/- 0.6 cm/year to 7.2 +/- 0.8 cm/year) and
      controls. However, the linear acceleration of growth velocity on GH therapy was
      significantly slower in thalassaemic children (3.3 +/- 0.3 cm/year increment)
      compared with those with CSS (5.3 +/- 0.4 cm/year increment) and GHD (6.9 +/- 1.2
      cm/year increment) (P < 0.05). Their circulating IGF-I concentration (105 +/- 36
      ng/ml) was significantly lower than those for CSS (246 +/- 58 ng/ml) and GHD (189
      +/- 52 ng/ml) after 1 year of GH therapy. These data prove that some children
      with beta-thalassaemia major have a defective GH-IGF-I-IGFBP-3 axis and suggest
      the presence of partial resistance to GH.

PMID- 9578507
TI  - GH dependence and GH withdrawal syndrome in GH treatment of short normal
      children: evidence from growth and cardiac output.
AB  - The child's age is a significant determinant of the outcome of GH therapy;
      prepubertal children respond better on both short term and long term growth,
      whereas adolescents tend to accelerate their bone maturation more than growth.
      The present study was designed to evaluate the efficacy of an interrupted GH
      therapy protocol of young, short normal children. GH was given for a period of 3
      years, or until they reached the 25th percentile, then discontinued at a young
      age (not more than 9 years), and then the children's growth followed until final
      height. Yet, after discontinuation of GH therapy, growth came close to a complete
      stand-still. The present report focuses on describing the period beyond GH
      withdrawal and its impact on growth and cardiac performance. Twenty-two children
      received daily s.c. injections of 0.9 mg/m2 hGH and 12 children were the control,
      untreated group. Growth and echocardiography were followed during therapy and 2
      years thereafter. During GH treatment growth velocity accelerated markedly over
      the first year; it slowed down over the second and third years, and decelerated
      after GH withdrawal to a velocity that was significantly lower than pretreatment
      values. Growth rate remained low for the next year, and recovered to pretreatment
      velocity by the fourth semiannual measurement. To evaluate the role of the GH-IGF
      I axis during the growth deceleration, serum IGF-I, insulin-like growth factor
      binding protein-3 (IGFBP-3), and an arginine stimulation test were performed at
      1, 3 or 6 months after GH withdrawal, and compared with pretreatment response. GH
      response was 70% of pretreatment values by 1 month and recovered completely by 3
      months post treatment. Serum IGF-I and IGFBP-3 levels were normal throughout. End
      systolic and end-diastolic left ventricular dimensions as well as cardiac output
      did not change during the 2 year course of GH therapy, but fell significantly
      during the initial 6 months of GH withdrawal. Thus, daily injections of GH to
      prepubertal short normal children is associated with development of drug
      dependence, followed during the abstinence period by deceleration of growth and
      reduction of cardiac output to levels that are lower than pretreatment values.
      After GH therapy for 30-36 months the withdrawal syndrome persists for 18 months,
      and is not induced by alterations of serum levels of GH or IGF-I.

PMID- 9578508
TI  - Effects of growth hormone treatment on the leptin system and on energy
      expenditure in abdominally obese men.
AB  - The present study has examined the short- and long-term effects of growth hormone
      (GH) treatment on the leptin system and energy expenditure. Thirty male
      individuals with abdominal obesity were randomised to GH or placebo treatment in
      a 9-month, double-blind study. The dose of GH was 9.5 microg/kg, administered
      subcutaneously every evening. Serum leptin concentrations were measured by a
      human leptin RIA. Total RNA was isolated from adipose tissue biopsies and leptin
      mRNA levels were determined by a semi-quantitative reverse transcriptase-PCR
      assay. Body composition was determined by potassium-40 and the basal metabolic
      rate (BMR) was measured by a computerised, ventilated, open-hood system. As
      compared with placebo, an overall decrease in serum leptin concentrations as
      assessed by the area under the curve (AUC) (P < 0.05) and an increase in BMR
      (AUC, P < 0.05) were observed during GH treatment. The overall GH-induced changes
      were due to marked changes in serum leptin concentrations and BMR after 6 weeks
      of treatment. After 9 months of GH treatment there was a significant reduction in
      body fat (BF) while serum leptin concentrations and BMR did not differ from
      baseline values. Leptin mRNA levels did not change over the study period. We
      speculate that long-term GH treatment induces a new energy balance steady state
      with decreased BF stores. The effects of GH on the leptin system is suggested to
      be of importance for the maintenance of a lower BF mass.

PMID- 9578509
TI  - Hypoleptinemia in patients with anorexia nervosa: loss of circadian rhythm and
      unresponsiveness to short-term refeeding.
AB  - Leptin is a protein encoded by the ob gene that is expressed in adipocytes and
      regulates eating behavior via neuroendocrine mechanisms. Plasma leptin levels
      have been shown to correlate with weight and body fat in normal, obese and
      anorexic subjects. In the last of these populations, the dynamic profile of
      plasma leptin levels during short-term refeeding has never been assessed. We thus
      investigated basal plasma leptin levels in 29 female patients with anorexia
      nervosa (AN) (age 21.9 +/- 1.4 years, body mass index (BMI) 15.2 +/- 0.3 kg/m2)
      and in 80 normal female controls (age 21.2 +/- 0.2 years, BMI 20.3 +/- 0.3 kg/m2,
      mean +/- S.E.M.). Basal plasma leptin levels in AN were decreased by 77% compared
      with controls (2.5 +/- 0.2 vs 11.1 +/- 0.7 ng/ml, P < 0.0001). In both AN
      subjects and controls, plasma leptin levels correlated significantly with BMI (r2
      = 0.448, P < 0.0001 and r2 = 0.339, P < 0.0001 respectively). Five AN patients
      (four female, one male, age 22.0 +/- 4.7 years, BMI 14.2 +/- 0.4 kg/m2, body fat
      4.3 +/- 0.9 kg or 11.0 +/- 1.9% of body weight, basal metabolic rate (BMR) 958 +/
      122 kcal/day) were studied during a 3-day refeeding period and compared with
      eight control subjects (two male, six female, age 25.7 +/- 1.2 years, BMI 21.3 +/
      0.8 kg/m2, body fat 15.1 +/- 0.9 kg or 24.6 +/- 1.7%, BMR 1455 +/- 78 kcal/day)
      submitted to 36-h fasting. The amount of calories administered was based on BMR +
      20% (carbohydrate 60%, protein 17%, fat 23%). In contrast to the rise in leptin
      levels that occurred during refeeding after a prolonged fast period in normal
      subjects, plasma leptin levels remained low and unchanged throughout the 3 days
      of renutrition in AN patients. The circadian rhythm of leptin was also completely
      abolished. This contrasted with the preserved circadian variations of cortisol,
      whose mean levels were increased. In conclusion, we confirmed that plasma leptin
      levels are low in AN and correlate with body weight. We further demonstrated that
      plasma leptin levels do not respond to short-term refeeding in anorexic patients
      in whom circadian variations are not restored, which suggests that the acute
      regulation of leptin by positive changes in energy balance is not preserved under
      a critical threshold of body fat.

PMID- 9578510
TI  - Serum levels of 3alpha-androstanediol glucuronide in hirsute and non hirsute
      women.
AB  - This study has evaluated the behaviour of 3alpha-androstanediol glucuronide
      (3alpha-diol G) in 170 women of whom 85 had polycystic ovary syndrome (PCOS), 35
      had idiopathic hirsutism (IH) and 50 had regular cycles (control group). Of the
      women with PCOS, 45 were hirsute (PCOS-H) and 40 were non hirsute (PCOS-NH).
      Women in the control group were not hirsute. Hirsutism was assessed by the same
      physician using the Ferriman-Gallway score. The body mass index (BMI) was
      estimated in all of the women. Plasma concentrations of 3alpha-diol G were
      elevated only in hirsute patients, both with PCOS and with IH. Even in PCOS-NH,
      concentrations of 3alpha-diol G were higher compared with controls (P < 0.001),
      but significantly lower (P < 0.001) than those of the PCOS-H and of the IH
      groups. The behaviour of 3alpha-diol G was not affected by BMI.

PMID- 9578511
TI  - Second trimester levels of maternal serum total activin A and placental
      inhibin/activin alpha and betaA subunit messenger ribonucleic acids in Down
      syndrome pregnancy.
AB  - OBJECTIVES: Previous data have shown that inhibin A (alpha/betaA) is increased
      about twofold in maternal serum samples from Down syndrome pregnancy. Our
      objectives were to determine whether activin A (betaA/betaA) was similarly
      increased in maternal serum from pregnancies affected with fetal Down syndrome,
      and to investigate whether increased expression of each inhibin/activin subunit
      occurred in placental tissue from cases of fetal Down syndrome. DESIGN AND
      METHODS: Maternal serum total activin A levels were measured in 20 cases of fetal
      Down syndrome and 100 unaffected pregnancy samples. In addition, analysis of
      inhibin/activin alpha and betaA subunit mRNA levels was performed in placental
      tissue extracts from six cases of fetal Down syndrome and six tissues with a
      normal karyotype. RESULTS: The median total activin A level in the Down syndrome
      cases was 0.82 MoM (multiples of the median); values did not differ significantly
      (P = 0.36, Mann-Whitney U analysis) from those in unaffected pregnancies. The
      inhibin alpha subunit/GAPDH mRNA ratio, but not that of betaA subunit/GAPDH mRNA,
      was significantly greater (P < 0.01, ANOVA) in placental tissue from Down
      syndrome than in control placental tissue. CONCLUSIONS: Unlike inhibin A, activin
      A is not significantly increased in Down syndrome relative to unaffected
      pregnancy. Furthermore, increased amounts of maternal serum inhibin A in Down
      syndrome pregnancy probably result from increased placental expression of inhibin
      alpha, but not betaA, subunit.

PMID- 9578512
TI  - Hypothalamo-pituitary-adrenal axis and adrenal function before and after
      ovariectomy in premenopausal women.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis is modulated by sex hormones. Few
      data exist on the relation between acute estrogen deficit and HPA axis response
      to corticotropin-releasing hormone (CRH). The effects of a sudden drop in
      estradiol levels on basal and CRH-stimulated levels of ACTH, cortisol,
      testosterone, androstenedione and 17-hydroxyprogesterone (17-OHP) were assessed
      in nine premenopausal women (44-48 years of age), before and after ovariectomy.
      The CRH test was performed before and 8 days after ovariectomy. A significant
      reduction in ACTH and adrenal steroids but not in cortisol response to CRH was
      observed after ovariectomy. The ratio of deltamax androstenedione/17-OHP after
      CRH stimulation was substantially the same before and after ovariectomy, whereas
      deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing
      increased 21- and 11beta-hydroxylase activity. The results show that the acute
      estrogen deficit induces changes in the HPA axis characterized by reduced
      stimulated secretion of ACTH and steroids but normal stimulated cortisol
      production.

PMID- 9578514
TI  - Response to European Journal of Endocrinology 1997 137 459-466 and 450-452:
      Effect of GH on lipoprotein (A) in GH deficiency.

PMID- 9578513
TI  - Expression of adrenomedullin and adrenomedullin mRNA in ectopic ACTH-secreting
      tumors.
AB  - OBJECTIVE: To study the expression of adrenomedullin, a potent vasodilator
      peptide originally isolated from a pheochromocytoma, in ectopic ACTH-secreting
      tumors. METHODS: Tumor tissue concentrations of adrenomedullin, calcitonin gene
      related peptide, neuropeptide Y, endothelin-1, corticotropin-releasing hormone
      and ACTH were measured in three ectopic ACTH-secreting tumors by RIA. The
      expression of adrenomedullin mRNA was examined by northern blot analysis of
      tissue from one of the tumors. RESULTS: Immunoreactive adrenomedullin was
      detected in tumor tissues of three ectopic ACTH-secreting tumors (0.60-18.5
      pmol/g wet weight). Calcitonin gene-related peptide, neuropeptide Y, endothelin-1
      and corticotropin-releasing hormone were also detected in the tumor tissues. The
      tumor tissue concentrations of immunoreactive adrenomedullin were comparable to
      those of these four peptides, but much lower than those of ACTH. Northern blot
      analysis showed the expression of adrenomedullin mRNA in one tumor from which
      sufficient tissue was available for such study. The plasma concentration of
      immunoreactive adrenomedullin was increased in one patient (41.3 pmol/l, control
      13.5 +/- 3.6 pmol/l, mean +/- S.D., n = 12). CONCLUSIONS: These results suggest
      that adrenomedullin is produced by ectopic ACTH-secreting tumors, together with
      other neuropeptides, and raise the possibility that adrenomedullin is related to
      the pathophysiology of these tumors.

PMID- 9578516
TI  - Cross-linked growth hormone dimers have enhanced biological activity.
AB  - In this study we have investigated the effect on the bioactivity of pituitary
      derived human growth hormone (hGH) and recombinant bovine (b) GH after the
      addition of various concentrations of the water soluble cross-linking agent 1
      ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC; 6.25-100 mg/ml). The biological
      activity of resulting cross-linked reactions were determined by its ability to
      promote incorporation of 35SO4(2-) into costal cartilage of hypopituitary Snell
      dwarf mice in vivo. Administration of EDC-treated hGH solutions resulted in a
      significant enhancement of hormone activity in vivo compared with non-cross
      linked samples. A similar significant enhancement of bGH activity in vivo was
      also observed when solutions containing recombinant bGH were cross-linked using
      EDC. For both hGH and bGH the degree of enhancement appears to be dose-dependent
      for the concentration of EDC (6.25-100 mg/ml for hGH; 6.25-50 mg/ml for bGH)
      present in the cross-linking reactions. SDS-PAGE analysis of EDC cross-linked
      solutions containing hGH and bGH spiked with 125I-hGH and 125I-bGH respectively
      revealed that dimeric GH was the primary cross-linked component. Increasing the
      concentration of EDC in cross-linking reactions resulted in increased formation
      of dimeric hGH and bGH. There was a significant correlation between the amount of
      GH dimer present and the increase in biological activity, suggesting that GH
      dimers were responsible for the enhanced biological activity. This was confirmed
      by the enhanced biological activity of a purified preparation of EDC cross-linked
      dimeric hGH. In conclusion, covalently cross-linked GH dimers reported here have
      enhanced bioactivity in vivo. However, since naturally occurring GH dimers are
      known to have reduced biological activity, this work suggests that the structure
      of EDC cross-linked GH dimers differs fundamentally from that of native dimeric
      hGH.

PMID- 9578515
TI  - Evidence for modulation of osteocalcin containing gamma-carboxyglutamic acid
      residues synthesis by insulin-like growth factor-I and vitamin K2 in human
      osteosarcoma cell line MG-63.
AB  - The effect of insulin-like growth factor-I (IGF-I) and 2-methyl-3-all-trans
      tetraphenyl-1,4-naphtoquinone (vitamin K2) on the synthesis of osteocalcin
      containing gamma-carboxyglutamic acid (Gla) residues which is the physiologically
      relevant form in bone metabolism was studied in cultured human osteoblast-like
      (MG-63) cells. Both IGF-I and vitamin K2 stimulated 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3)-induced osteocalcin containing Gla secretion in a concentration
      dependent manner. This stimulatory effect of IGF-I and vitamin K2 was additive.
      Vitamin K2-enhanced osteocalcin containing Gla secretion was selectively
      suppressed by 3-(alpha-acetonyl-benzyl)-4-hydroxy-coumarin (warfarin). The
      stimulatory effect of IGF-I was completely abolished by the presence of
      cycloheximide; in contrast the effect of vitamin K2 was still observed in the
      presence of cycloheximide. Treatment of MG-63 cells with IGF-I caused an
      approximately 2.2-fold increase in osteocalcin mRNA levels (determined by reverse
      transcription-polymerase chain reaction). Vitamin K2 had no effect on either the
      stimulation of mRNA level by IGF-I or the basal level. IGF-I-stimulated
      osteocalcin containing Gla secretion was inhibited by one of its binding proteins
      (insulin-like growth factor binding protein-4) in a concentration-dependent
      manner. These findings suggest that the modes of action of IGF-I and vitamin K2
      on 1.25(OH)2D3-induced osteocalcin containing Gla secretion in MG-63 cells are
      different.

PMID- 9578517
TI  - Effects of N-methyl-D-aspartic acid and kainic acid on prolactin secretion in
      hyper- and hypoprolactinaemic conditions.
AB  - OBJECTIVE: The stimulatory and inhibitory effects of N-methyl-D-aspartic acid
      (NMDA) and kainic acid on prolactin (PRL) secretion have been correlated with the
      serum prolactin concentrations before drug administration. In the present
      experiments, we analysed the role of NMDA and kainic acid in PRL secretion in
      females with different serum concentrations of PRL. METHODS: Hypoprolactinaemic
      females were obtained by ovariectomy or after administration of
      diethyldithiocarbamate (an inhibitor of dopamine-beta-hydroxylase). Chronic
      hyperprolactinaemia was induced by neonatal administration of testosterone or
      oestradiol and acute hyperprolactinaemia was induced either by administration of
      alpha-methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase) or by ether
      exposure. To analyse the role of dopamine in the effects of NMDA, we measured
      pituitary concentrations of dopamine after NMDA treatment and the effects of
      pretreatment with domperidone. RESULTS: (1) NMDA, but not kainic acid, stimulated
      PRL release in cyclic females. This effect was independent of serum PRL
      concentrations and was not accompanied by a decrease in pituitary concentrations
      of dopamine. (2) NMDA did not change PRL secretion in neonatally androgenized
      females, whereas NMDA and kainic acid inhibited PRL release in neonatally
      oestrogenized females. The inhibitory effects of NMDA and kainic acid were
      blocked by domperidone. (3) Kainic acid inhibited PRL secretion in prepubertal
      hyper- and hypoprolactinaemic rats. (4) Hyperprolactinaemia induced by ether
      stress was counteracted by administration of NMDA and kainic acid. CONCLUSIONS:
      (a) NMDA has a dual effect on prolactin secretion that is independent of prior
      prolactin concentrations and of dopamine activity, but kainic acid is only
      inhibitory. (b) The stimulatory or inhibitory effects of NMDA and kainic acid on
      PRL secretion were not strictly related to basal PRL concentrations and
      necessarily involved a change in the secretion of prolactin releasing factors, as
      no correlations were observed between changes in pituitary concentrations of
      dopamine and serum PRL concentrations. (c) Females rendered hyperprolactinaemic
      by neonatal administration of testosterone or oestradiol responded differently
      after NMDA administration. (d) NMDA and kainic acid blocked the mechanisms
      involved in stress-induced PRL secretion.

PMID- 9578518
TI  - Role of nitric oxide synthase in release of endothelin from cultured human
      endometrial cells.
AB  - The aim of this study was to investigate the influence of the nitric oxide/nitric
      oxide synthase (NO/NOS) system on the release of endothelin-1 (ET-1) in human
      endometrial cells. Human endometrial stromal cells in secretory phase were
      incubated for 72 h in serum-free RPMI 1640 medium in the absence or presence of
      different concentrations of interleukin-1beta (IL-1beta) and NG-monomethyl-L
      arginine (LNMMA), a specific competitive inhibitor of NOS. ET-1 released from the
      cultured cells into the medium was determined by specific RIA. In all the
      experiments at various times, IL-1beta significantly increased the release of ET
      1. LNMMA significantly attenuated the release of ET-1 when the cells were
      cultured with both IL-1beta and LNMMA, but LNMMA alone had no effect on ET-1
      release. These results suggest that the NO/NOS system in human endometrium is
      involved in the regulation of ET-1 release via IL-1beta secretion. It can also be
      inferred that NO and ET-1 control the functions of endometrium in close
      association with IL-1beta.

PMID- 9578519
TI  - Felbamate: 1997 update.

PMID- 9578520
TI  - Evaluation of case reports of aplastic anemia among patients treated with
      felbamate.
AB  - PURPOSE: Felbamate (FBM) is a new antiepileptic drug (AED) that is often
      effective in seizure disorders refractory to other treatments; its use has been
      greatly restricted after cases of aplastic anemia were reported. To elucidate the
      putative association between FBM and aplastic anemia, we made a detailed
      evaluation of the first 31 reports. METHODS: Hematologic review according to the
      criteria of the International Agranulocytosis and Aplastic Anemia Study (IAAAS)
      confirmed 23 cases (74%) as aplastic anemia; FBM was judged to be the only
      plausible cause for three; confounding (mostly by other drugs) was considered
      possible, but FBM remained the most likely cause for 11; and there was at least
      one other plausible cause for 9. RESULTS: Using a denominator from sales data of
      110,000 persons exposed and a numerator of the cases for which FBM was considered
      the only plausible cause, we established a lower limit of incidence of 27 cases
      of aplastic anemia per million users as compared with the general population rate
      of 2.0 per million per year. With all confirmed cases used as the numerator, the
      upper limit of incidence was 209 per million. The 'most probable" incidence was
      estimated to be 127 per million. CONCLUSIONS: Intensive, systematic investigation
      can maximize the utility of case reports for assessing risks of newly released
      drugs. The present evaluation confirmed an association between FBM and aplastic
      anemia; however, confounding was significant for most cases and there was a
      tenfold range in the "best case" and "worst case" incidence estimates among
      users.

PMID- 9578521
TI  - Vigabatrin versus ACTH as first-line treatment for infantile spasms: a
      randomized, prospective study.
AB  - PURPOSE: To compare the efficacy and tolerability of vigabatrin (VGB) and
      adrenocorticotrophic hormone (ACTH) as first-line therapy in infantile spasms.
      METHODS: Forty-two infants (22 males, 20 females) aged 2-9 months with newly
      diagnosed infantile spasms, were included in the trial. Patients were randomized
      to receive VGB 100-150 mg/kg/day or Depot ACTH 10 IU/day. The alternative drug
      was given if spasms were not controlled within 20 days or in cases of intolerance
      to initial therapy. Twenty-three patients (7 cryptogenic, 16 symptomatic)
      received VGB as first-line therapy; 19 patients (8 cryptogenic, 11 symptomatic)
      received ACTH as the first drug. RESULTS: Cessation of spasms was observed in 11
      (48%) of the patients randomized to VGB and in 14 (74%) of those randomized to
      ACTH. Response to VGB was observed within 1-14 days, but two-thirds of patients
      (7/11) responded within 3 days. In the group treated with VGB, side effects such
      as drowsiness, hypotonia and irritability were observed in 13% of patients,
      compared with 37% in the group treated with ACTH. VGB was more effective than
      ACTH as treatment for cerebral malformations or tuberous sclerosis, whereas ACTH
      proved more effective in perinatal hypoxic/ischemic injury. The efficacy of the
      two drugs was similar in cryptogenic cases. Disappearance of interictal EEG
      abnormalities occurred sooner in patients randomized to ACTH than in those who
      received VGB as initial therapy. During the second phase, the alternative drug
      was given to the resistant patients. Spasms ceased in 2 of 5 patients treated
      with VGB and in 11 of 12 patients treated with ACTH. After 3 months, relapses of
      spasms were observed in 6 patients treated with ACTH and in 1 treated with VGB.
      VGB produced a therapeutic response in nearly half the patients receiving this
      drug. CONCLUSIONS: Our data lend further support to the view that VGB may be
      considered a first-choice drug in the treatment of IS.

PMID- 9578522
TI  - Prevalence, classification, and severity of epilepsy and epileptic syndromes in
      children.
AB  - PURPOSE: To determine the point prevalence of active childhood epilepsy in a
      defined area and evaluate the usefulness of ILAE classification of seizures, and
      epilepsies/syndromes with special interest in severe epilepsies. METHODS: By
      using the latest ILAE International Classification of Epileptic Seizures (ICES,
      1981) and Epilepsies and Epileptic Syndromes (ICE, 1989), we determined the age-
      and sex-specific prevalence rates of epilepsy, type of seizures, epilepsies, and
      recognizable epileptic syndromes, as well as the proportion of severe cases in
      each seizure/epilepsy/syndrome category in all children 0-15 years of age from a
      geographically defined area in Finland. All medical records, neurophysiological
      recordings and available clinical data were reviewed retrospectively. RESULTS:
      Point prevalence of active epilepsy on December 12, 1992 was 3.94 per 1,000.
      According to ICES/ICE, we were able to classify 96% of seizures and 90% of
      epilepsies and syndromes. Generalized seizure and epilepsy/syndrome types were
      more prevalent in children 0-6 years of age and partial/localization-related in
      children 6-15 years of age. Epilepsy was intractable in 17% of all cases and
      correlated significantly with symptomatic etiology and early onset of epilepsy,
      as well as with additional neuroimpairments. CONCLUSIONS: A considerable number
      of cases fell into the nonspecific categories of ICE, which limits the value of
      present epilepsy/syndrome classification in terms of prognosis, prediction, and
      indication for special investigations in individual cases. A number of
      intractable cases was relatively low, indicating good prognosis in many childhood
      epilepsies, especially when additional neuroimpairments are absent.

PMID- 9578523
TI  - Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta
      children.
AB  - PURPOSE: To determine the prevalence and descriptive epidemiology of Lennox
      Gastaut Syndrome (LGS) among metropolitan Atlanta children. METHODS: We conducted
      a population-based study of LGS as part of the Metropolitan Atlanta Developmental
      Disabilities Study (MADDS) using a multiple-source surveillance system for
      epilepsy and developmental disabilities. Children were defined as having LGS if
      they had onset of multiple seizure types before age 11 years, with at least one
      seizure type resulting in falls, and an EEG demonstrating slow spike-wave
      complexes (<2.5 Hz). Mental retardation (MR) was not used as a diagnostic
      criterion. RESULTS: The lifetime prevalence of LGS at age 10 years was
      0.26/1,000. Ninety-one percent of those with LGS had MR (IQ < or = 70), and 39%
      had a history of infantile spasms (IS). A comparison of children with LGS and
      those with multiple seizure types without slow spike-wave complexes demonstrated
      that those with LGS were more likely to have MR, history of IS, and multiple
      disabilities (MR, cerebral palsy, blindness, hearing impairment). Seventeen
      percent of all children in Atlanta with profound MR (IQ < 20) had LGS.
      CONCLUSIONS: LGS accounts for only 4% of all childhood epilepsy, yet is a
      significant contributor to childhood morbidity.

PMID- 9578525
TI  - Electrocerebral recovery during the intracarotid amobarbital procedure: influence
      of interval between injections.
AB  - PURPOSE AND METHODS: During the intracarotid amobarbital procedure (IAP) at the
      University of Michigan, continuous scalp EEG monitoring guides the timing for
      presentation of memory items and postinjection testing. Most of our patients have
      undergone bilateral injections. The interval between injections varied from 22 to
      60 min, depending on the test and recovery time, as well as the time to
      catheterize the second side. After noting a trend toward prolonged electrographic
      recovery following the second injection, we tested our clinical impression that
      recovery of the second hemisphere may be influenced by (a) the time between
      injections and (b) which hemisphere is injected first (epileptogenic or
      nonepileptogenic). To study these questions, we analyzed EEG recovery data from
      48 consecutive IAPs. Approximately half the patients had the epileptogenic side
      injected first. RESULTS: We found that (a) electrographic recovery after the
      second injection is prolonged if the interval between bilateral injections is
      less than 40 minutes and (b) electrographic recovery is more rapid after
      injection of the epileptogenic hemisphere. CONCLUSIONS: We now recommend waiting
      at least 45 min between injections. The pathophysiology of more prolonged
      amobarbital effect on the nonepileptogenic hemisphere than on the epileptogenic
      hemisphere remains unclear.

PMID- 9578524
TI  - Quantitative MRI in outpatient childhood epilepsy.
AB  - PURPOSE: In adult studies, MRI volumetrics is a proven technique in presurgical
      assessment of epilepsy. Hippocampal volume loss is maximal in the syndrome of
      mesial temporal lobe epilepsy. We aimed (a) to validate this methodology in a
      pediatric outpatient epilepsy population (b) to determine the relationship of
      hippocampal asymmetry (HA) to epileptic syndromes and risk factors. METHODS: Two
      neurologists classified the epileptic syndrome in 79 pediatric outpatients,
      according to the International Classification of Epilepsies and Epileptic
      Syndromes (ILAE). Hippocampal volumetrics were performed in all patients. HA was
      defined according to adult control values. RESULTS: Inter-rater variability on
      measurement of HA was very small (Correlation of test retest of 0.97 on 17
      children <3 years old). The rate of HA was 44/79 (57%). In 21 patients, (27%)
      potentially epileptogenic lesions (other than HA) were identified (cerebral
      dysgenesis n = 11). HA was present in 9/15 (60%) of temporal lobe epilepsy and in
      15/28 (54%) extratemporal onset epilepsy and 5/11 (46%) of generalized
      symptomatic epilepsy. Analysis confined to <13 years also showed HA was not
      specific for epileptic syndrome. There was no significant association of febrile
      convulsions (13%) with HA or temporal lobe epilepsy. CONCLUSIONS: There is a high
      incidence of HA in childhood epilepsy. HA was not confined to clinically defined
      temporal lobe epilepsy. The poor correlation of epileptic syndrome to
      quantitative MRI findings may be due to the inadequacies of epilepsy
      classification in the younger child, with the clinical semiology providing
      misleading localizing information. Normative childhood data for hippocampal
      volumes and symmetry is needed.

PMID- 9578526
TI  - Relations between EEG seizure morphology, interhemispheric spread, and mesial
      temporal atrophy in bitemporal epilepsy.
AB  - PURPOSE: A strong relation exists between lateralization of seizure onset in
      temporal-lobe epilepsy and atrophic mesial structures measured by volumetric
      magnetic resonance imaging (MRI). We examined whether this relation extended to
      subregions of the mesial temporal lobe and whether the trend for seizures to
      spread contralaterally could be related to the localization of atrophy. METHODS:
      We analyzed 362 seizures (with and without clinical signs) from 23 patients
      having bitemporal epilepsy in whom intracerebral electrodes were implanted for
      presurgical evaluation. Patients had measurements of hippocampal and amygdala
      volumes, including comparison with normal controls. We assessed on EEG the
      lateralization and localization of seizure onset and the trend to spread to the
      contralateral side (proportion of seizures that spread for each patient). We
      included all seizures, independent of the presence of clinical manifestations.
      These features were related to presence and localization of atrophy. RESULTS:
      Among the 19 patients with mesial atrophy, agreement between side of prevalent
      seizure onset and predominant atrophy was found in 10 (53%). From 99 seizures
      starting in a temporal lobe with atrophy limited to the hippocampus, 67% started
      simultaneously in amygdala and hippocampus, 20% in hippocampus, and 13% in
      amygdala. From 137 seizures starting in a temporal lobe with amygdala and
      hippocampal atrophy, 47% started in amygdala and hippocampus, 48% in hippocampus,
      and 5% in amygdala. The trend to spread was 45% to the most atrophic side and 62%
      to the normal or less atrophic side. CONCLUSIONS: When examining amygdala and
      hippocampus in this group of patients with bitemporal epilepsy, regions of
      seizure onset did not correspond to regions of predominant atrophy. The
      likelihood that seizures spread contralaterally was not influenced by atrophy in
      the region targeted by the spread. Precise relation between mesial temporal
      atrophy and seizures remain to be elucidated.

PMID- 9578527
TI  - Association of combined MRI, interictal EEG, and ictal EEG results with outcome
      and pathology after temporal lobectomy.
AB  - PURPOSE: Magnetic resonance imaging, interictal scalp EEG, and ictal scalp EEG
      each have been shown to localize the primary epileptic region in most patients
      with mesial-basal temporal lobe epilepsy (MBTLE), but the association of surgical
      outcome and pathology with each combination of these test results is not known.
      METHODS: We reviewed the MRI, interictal scalp EEG, and ictal scalp EEG results
      of 90 consecutive patients with MBTLE. Twelve patients were excluded from the
      analysis because inconclusive bitemporal intracranial EEG results precluded
      anterior temporal lobectomy (ATL); none had concordant MRI and interictal scalp
      EEG results. We compared all combinations of presurgical MRI, interictal EEG, and
      ictal EEG results to seizure outcome and tissue pathology in the 78 patients who
      underwent an ATL. RESULTS: Forty-eight (61%) patients had concordant lateralized
      MRI and interictal EEG temporal lobe abnormalities, with no discordant ictal EEG
      results; 77% of these patients were seizure-free after ATL. Concordance of MRI
      and interictal EEG abnormalities correlated with seizure cessation (p < 0.05),
      compared to all combinations with discordant or nonlateralizing MRI and
      interictal EEG results. Mesial temporal sclerosis (MTS) was confirmed
      pathologically in about 80% of both groups (p = 0.5). Outcome in patients with
      concordant MRI and ictal EEG with nonlateralizing interictal EEG was
      significantly worse than combinations with concordant MRI and interictal EEG (p <
      0.02). CONCLUSIONS: Compared to other combinations of test results, concordance
      of MRI and interictal EEG is most closely associated with surgical outcome in
      MBTLE. However, most selected patients have pathologic confirmation of MTS
      regardless of test results or outcome. This information may be useful for
      planning the presurgical evaluation of patients with medically intractable MBTLE.

PMID- 9578528
TI  - Localization of epileptic auras induced on stimulation by subdural electrodes.
AB  - PURPOSE: This study evaluates the localization of stimulation-induced auras (SIA)
      and tries to determine whether the SIA can help to define the boundaries of
      resection in epilepsy surgery. METHODS: Using subdural grid electrodes, 31
      patients with drug resistant focal epilepsy were examined in a retrospective and
      prospective study lasting 2 years. RESULTS: On stimulation by subdural
      electrodes, we elicited habitual auras in 16 patients (52%). The zone of SIA
      overlapped the epileptogenic lesion in 12 patients (75%), the EEG seizure onset
      zone in 12 patients (75%), and the irritative zone of interictal spikes in eight
      patients (50%). Postoperative results showed a significant correlation with the
      complete removal of the epileptogenic lesion (p < 0.001). Because the number of
      patients in the study was small, we could not find a significant correlation with
      the complete removal of the SIA zone, EEG seizure onset zone, and irritative
      zone. CONCLUSIONS: Our study confirms previous analyses which indicate that
      complete resection of the epileptogenic lesion is essential to achieve a good
      outcome. Frequent overlap of the SIA zone with the epileptogenic lesion and the
      EEG seizure onset zone indicates proximity of the SIA with the epileptogenic
      zone. Nevertheless, this study does not support the concept that the SIA zone and
      the EEG seizure onset zone have additional value in defining the boundaries of
      resection in epilepsy surgery. Three case presentations suggest that SIA result
      from facilitated pathways between the stimulated cortex, the epileptogenic zone
      around the lesion, and the symptomatogenic zone. Functional reorganization in the
      vicinity of the cortical lesion cannot be ruled out but was not seen in our
      patients. Thus, SIA often do not reflect the normal function of the stimulated
      underlying cortex.

PMID- 9578529
TI  - Pre- and postoperative socioeconomic development of 151 patients with focal
      epilepsies.
AB  - PURPOSE: We evaluated retrospectively the socioeconomic development of epilepsy
      patients after temporal or extratemporal epilepsy surgery and analyzed the
      relationship to clinical and neuropsychological data. METHODS: 151 patients (from
      ages 11-65 years; mean postoperative followup: 3 years) replied to a structured
      questionnaire, which referred to objective data of the patient's educational and
      vocational development. Neuropsychological data were obtained from pre- and
      postoperative (1-year follow-up) examinations. RESULTS: The preoperative
      development data indicated that patients exposed to epilepsy at any developmental
      stage had a higher prevalence of educational/vocational difficulties as compared
      with patients with a later onset of epilepsy. Postoperatively, the integration of
      the formerly unemployed improved and the unemployment rate decreased from 33 to
      16%. Out of those patients who had been schooled or who were employed, 79%-91%
      made progress in development, or were at least able to keep their status. Only 2
      of 14 patients, who had been retired early because of their epilepsy, returned to
      employment. In general, a deterioration of the socioeconomic status was
      significantly related to insufficient seizure control. A reemployment of patients
      who were formerly unemployed depended mainly on age and neuropsychological
      outcome. CONCLUSIONS: Our results suggest that early and successful surgical
      intervention improves or at least maintains the socioeconomic situation,
      especially the employment status.

PMID- 9578530
TI  - The contribution of tertiary centers to the quality of the diagnosis and
      treatment of epilepsy. Osservatorio Regionale per l'Epilessia (OREp), Lombardy.
AB  - PURPOSE: A survey was made of a network of 14 epilepsy centers in Italy to assess
      whether integrated diagnosis and treatment monitoring led to a more precise
      syndromic classification of the patients and a better response to treatment.
      METHODS: Data on the diagnosis and treatment of epilepsy and the degree of
      seizure control were recorded in a register on 2 separate occasions, on June 30,
      1990 (t0), before starting the integrated activities, and on June 30, 1992 (t1),
      on completion of a 2-year follow-up. Each patient's history was required to fit a
      specific category of the International Classification of the Epilepsies (ICE)
      (1). Response to treatment was classified as complete remission, occasional
      seizures, recurrent nonrefractory seizures, and drug-resistant epilepsy. A total
      of 3,469 patients of the ages of 4-80 years were enrolled. RESULTS: At t0, 44% of
      cases had localization-related epilepsy, 31% generalized epilepsy, 9%
      undetermined epilepsy, 6% special syndromes, and 10% epileptic syndromes with
      atypical features. At t1, the percentages in each category were 51, 27, 7, 6, and
      9%. The cases classified as "other" within each syndromic category at t0 were 11
      23% and remained unchanged at t1. Patients with symptomatic localization-related
      epilepsies were largely recoded as symptomatic or cryptogenic epilepsies. About
      one-third of patients with symptomatic generalized epilepsy were recoded as
      localization-related epilepsies. Nine percent of patients were classified as
      "uncertain" epilepsies at t0, and the same proportion at t1. However, many
      "uncertain" diagnoses became "definite" and vice versa. CONCLUSIONS: There was a
      slight increase in the proportion of patients achieving complete remission (from
      13 to 28%) and untreated patients (from 10 to 17%). Nine percent of patients
      unresponsive to treatment at t0 had achieved remission at t1. Drug resistance was
      confirmed in 78% of cases and was mostly independent of the therapeutic decision.
      Ten percent of cases achieved remission with unchanged or simplified treatment
      schedules.

PMID- 9578531
TI  - Short-term mortality after a first episode of status epilepticus.
AB  - PURPOSE: Studies evaluating short-term mortality among people who experience
      status epilepticus (SE) have produced conflicting results. Most studies are
      derived from clinical series with results affected by unspecified follow-up
      period and select referral of cases. This study was planned to evaluate short
      term mortality after a first episode of SE. METHODS: We performed a population
      based retrospective cohort study to determine the short-term mortality following
      a first episode of SE. Between January 1, 1965 and December 31, 1984, we studied
      all first episodes of afebrile SE who received medical attention in Rochester,
      Minnesota. Cases were followed until death or end of the study (February 1996).
      RESULTS: Mortality within the first 30 days was 19% (38 deaths out of 201
      incident SE). Thirty-four deaths (89%) occurred among those with nonfebrile acute
      symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE.
      Within the acute symptomatic group, after adjusting for age, there was a
      decreased risk of death in women (RR = 0.4; 95% CI: 0.2-0.9). No effect of
      duration or seizure type was shown after adjusting for other risk factors.
      CONCLUSIONS: One out of 5 subjects with SE died within the first 30 days. Short
      term mortality is associated with the presence of an underlying acute etiology.
      Among acute symptomatic cases, women had a decreased risk of dying.

PMID- 9578532
TI  - Scalp-recorded, ictal focal DC shift in a patient with tonic seizure.
AB  - PURPOSE: We recorded focal ictal DC shifts from scalp electrodes in a 9-year-old
      boy with intractable, clinically generalized tonic seizures. The patient had a
      high intensity signal abnormality of the left temporal cortex with thickening of
      the gyri on T2-weighted MRI. METHODS: Scalp digital EEGs were recorded using
      electrodes made of silver/silver chloride. The low frequency filter (LFF) was set
      at 0.016 Hz. Recorded seizures were subsequently analyzed with LFF settings of
      1.0, 0.016 and 0.03 Hz. RESULTS: All recorded seizures initially showed diffuse,
      low voltage, high frequency activity (electrodecremental pattern) followed 10-20
      s later by quasirhythmic activity over the left frontotemporal region. In two
      seizures, LFF of 0.016-0.03 Hz revealed a slow negative shift over the left
      frontotemporal area simultaneously with onset of the bilateral electrodecremental
      pattern. However, in the other seizures, this initial slow negative shift was
      obscured by artifacts. Subsequent electrocorticography (ECoG) delineated frequent
      epileptiform discharges in the left temporal as well as frontal cortex.
      CONCLUSIONS: Scalp-recorded ictal DC shifts may help identify focal epileptogenic
      brain area in patients with clinically generalized seizures although the
      technique is vulnerable to artifact.

PMID- 9578533
TI  - "Periodic" seizures.
AB  - PURPOSE: To describe regularly recurring ictal phenomena as recorded in a single
      patient whose seizure disorder related to a left temporal cavernous angioma.
      METHODS: Seizures were recorded by left temporal subdural strip electrodes which
      were bilaterally placed because of ambiguous seizure origin and right temporal
      memory dysfunction at Wada testing. Seizure length, interseizure intervals, and
      interseizure onset intervals were visually assessed. The coefficient of variation
      was used as an estimate of variability in seizure periodicity. RESULTS: Mean
      seizure durations varied from 68 to 95 s; coefficients of variation varied from
      0.08 to 0.18, values similar to other periodic biological phenomena. Mean daily
      seizure intervals varied from 96 to 152 s with coefficients of variation ranging
      from 0.12 to 0.35. Interseizure onset intervals had smaller coefficients of
      variation (0.03-0.20). Manifestations of these simple partial seizures included a
      rising epigastric sensation and nausea. CONCLUSIONS: Previously described
      periodic EEG phenomena are interictal events or appear with peripheral events of
      similar cadence. Therefore, we remain unaware of any documentation of periodic
      ictal electrographic events. The restricted propagation and duration of these
      recorded seizures may have simplified their pathophysiology allowing a
      stereotyped involvement of excitatory and inhibitory mechanisms producing the
      periodicity.

PMID- 9578534
TI  - Final report of the ILAE Commission on Economic Aspects of Epilepsy, 1994-1997.
      International League Against Epilepsy.

PMID- 9578535
TI  - Ictal laughter associated with paroxysmal hypothalamopituitary dysfunction
      (Epilepsia 1997;38:114-7).

PMID- 9578536
TI  - Case of a child with gelastic seizures and hypothalamic hamartoma.

PMID- 9578537
TI  - Case of a child with gelastic seizures and hypothalamic hamartoma.

PMID- 9578538
TI  - The development of antiepileptic drugs: current status and future directions.
      Introduction and symposium overview.

PMID- 9578539
TI  - Basic mechanisms of epilepsy: targets for therapeutic intervention.
AB  - Although a wide variety of drugs are available for treatment of epilepsy, many
      patients with epilepsy still experience uncontrolled seizures. In addition, there
      is a need for new drugs that can halt epileptogenesis after brain injury.
      Mechanisms that underlie seizure processes constitute potential target areas for
      the development of new antiepileptic drugs (AEDs). An understanding of the
      underlying mechanisms of interictal spike discharge and seizure spread is
      critical for the development of AEDs for treatment of partial seizures.
      Suppression of specific forms of voltage-dependent calcium currents and
      inhibition of GABA(B) receptor-mediated inhibition are two key target areas for
      new AEDs to treat primary generalized seizures. As researchers gain more
      understanding of the cellular, molecular, and genetic mechanisms underlying
      seizure propagation, we should be better able to develop therapeutic agents
      designed to suppress seizure-provoking mechanisms and to enhance the brain's
      natural protective mechanisms.

PMID- 9578541
TI  - Monotherapy clinical trials of new antiepileptic drugs: design, indications, and
      controversies.
AB  - The focus in assessing new antiepileptic drugs (AEDs) varies with the needs of
      the assessor. Patients and doctors seek evidence-based clinical information,
      regulatory agencies look for efficacy and safety, and the health-care industry
      demands data on the risk-benefit ratio attached to a product. The pharmaceutical
      companies attempt to satisfy the interests of all parties involved. Most new AEDs
      obtain a first license based on placebo-controlled, randomized clinical trials as
      add-on therapy in patients with chronic refractory partial epilepsy, a method
      which, in fact, explores the efficacy of different drug combinations rather than
      measuring the efficacy of the new drug itself. Although that methodology
      satisfies the requirements of the licensing authorities, it fails to provide the
      clinical community with the information necessary to make rational treatment
      decisions, as would be derived from monotherapy studies. This article reviews
      controversies surrounding monotherapy studies and the design of comparative
      monotherapy clinical trials. A persuasive argument can be made that the goal of
      clinical trial design should be ethically acceptable, clinically meaningful
      studies in which new AEDs are compared with optimal doses of standard AEDs to
      inform clinical practice, meet licensing requirements, guide reasonable marketing
      efforts, and allow appropriate reimbursement.

PMID- 9578540
TI  - Identification and preclinical testing of novel antiepileptic compounds.
AB  - Procedures for identifying novel antiepileptic drugs (AEDs) are changing and need
      to change more. Widespread reliance on two primary screens has led to the
      identification of novel compounds that resemble either phenytoin (suppressing
      high-frequency repetitive firing in cultured neurons and prolonging inactivation
      of voltage-dependent sodium channels identified by the maximal electroshock test)
      or benzodiazepines (potentiating the inhibitory effect of gamma-aminobutyric acid
      (GABA), identified by the threshold pentylenetetrazol test). Advances in
      molecular neurobiology have identified specific molecular targets (subunits of
      ion channels, neurotransmitter receptors, and transporters) and have made them
      available in a form permitting high-throughput screening. AEDs can be designed to
      interact with specific sites on the target molecules. Alternatively, the
      molecular screens can be used to identify active components in natural products,
      including folk remedies. Preclinical in vivo screens can be improved by using
      animals with genetic or acquired epilepsies that have similar modifications in
      the properties of the target molecules as do human epilepsy syndromes. Future
      work is likely to define molecular targets for AEDs that will block or reverse
      chronic epileptogenesis.

PMID- 9578542
TI  - Monotherapy trials of new antiepileptic drugs.
AB  - A number of clinical trials that test the efficacy and safety of the newer
      antiepileptic drugs (AEDs) have recently been concluded. Two dose-response trials
      in inpatients with refractory partial seizures and outpatients with newly
      diagnosed partial epilepsy established the efficacy of gabapentin as monotherapy.
      Lamotrigine was found to have efficacy similar to that of phenytoin and
      carbamazepine (CBZ) and to be better tolerated than CBZ in patients with newly
      diagnosed epilepsy. It was also shown to have efficacy as monotherapy in partial
      seizures, based on the results of an active controlled trial, and in the
      treatment of absence seizures, based on the results of a responder-enriched
      study. Topiramate as monotherapy was found to be efficacious for treatment of
      partial-onset seizures, based on the results of a single-center dose-response
      trial. A dose-response trial that tested the efficacy of tiagabine monotherapy in
      patients with refractory partial epilepsy was uninformative. Oxcarbazepine was
      found to be safe and efficacious in four comparative trials in patients with
      newly diagnosed epilepsy as well as in one placebo-controlled inpatient trial in
      patients with refractory partial seizures.

PMID- 9578543
TI  - Epilepsy genes and the genetics of epilepsy syndromes: the promise of new
      therapies based on genetic knowledge.
AB  - Treatment strategies based on the molecular biology of the epilepsies may soon
      become a reality. Critical steps in this process are identifying molecular
      genetic defects in specific epilepsies, understanding of the neurobiologic
      consequences of those defects, and developing methods to correct the molecular
      defects or their downstream consequences. Identification of molecular defects is
      easier in single-gene epilepsies than in those with complex inheritance, although
      the latter are more common. A number of epilepsies have been mapped and, in two
      cases, specific genes have been identified. Unverricht-Lundborg disease is caused
      by defects in the cystatin B gene, with absence of the gene product. Autosomal
      dominant nocturnal frontal lobe epilepsy in some families is caused by mutations
      in the alpha4-subunit of the nicotinic acetylcholine receptor gene. In vitro
      studies suggest that the mutations lead to impaired function of the acetylcholine
      receptor, raising the possibility of cholinergic therapy for this condition.
      Advances in the molecular biology of the epilepsies are likely to change our
      understanding radically and to allow opportunities to develop innovative new
      treatments for epilepsy.

PMID- 9578544
TI  - The problem of intractability: the continuing need for new medical therapies in
      epilepsy.
AB  - Treatment of epilepsy, one of the most common neurologic disorders, has evolved
      from "institutional" polytherapy to "dogmatic" monotherapy, and, most recently,
      to "rational" polypharmacy. The introduction of bromides for the treatment of
      epilepsy was followed first by phenobarbital and then by phenytoin as therapeutic
      options. Although attempts to combine medications were legion, none was supported
      by studies that demonstrated the benefit of such combinations. The issue of
      adverse effects became a principal argument in favor of monotherapy. Monotherapy,
      using newly developed drugs, avoided problems due to drug interactions but was
      ineffective in 20-30% of patients. A greater understanding of basic disease
      mechanisms and developments in molecular biology have led to an increased number
      of effective drugs for the estimated 6-12% of patients with epilepsy whose
      condition is intractable. Clinical research continues to build on the work of
      basic scientists in attempting to develop treatments based on a desire to move
      beyond the palliative and to affect the causative mechanisms of the disease.
      Novel medical approaches now under exploration include the use of drugs with
      complementary mechanisms of action, stimulation of various components of the
      nervous system, biochemical manipulations, focal intracerebral drug perfusion,
      and gene therapy.

PMID- 9578545
TI  - Interfacial activation of triglyceride lipase from Thermomyces (Humicola)
      lanuginosa: kinetic parameters and a basis for control of the lid.
AB  - A strategy is developed to analyze steady-state kinetics for the hydrolysis of a
      soluble substrate partitioned into the interface by an enzyme at the interface.
      The feasibility of this approach to obtain interfacial primary kinetic and
      equilibrium parameters is demonstrated for a triglyceride lipase. Analysis for
      phospholipase A2 catalyzed hydrolysis of rapidly exchanging micellar (Berg et al.
      (1997) Biochemistry 36, 14512-14530) and nonexchangeable vesicular (Berg et al.,
      (1991) Biochemistry 30, 7283-7291) phospholipids is extended to include the case
      of a substrate that does not form the interface. The triglyceride lipase (tlTGL)
      from Thermomyces (formerly Humicola) lanuginosa hydrolyzes p-nitrophenylbutyrate
      or tributyrin partitioned in the interface of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoglycerol (POPG) vesicles at a rate that is more than 100-fold higher than
      that for the monodispersed substrate or for the substrate partitioned into
      zwitterionic vesicles. Catalysis and activation is not seen with the S146A mutant
      without the catalytic serine-146; however, it binds to the POPG interface with
      the same affinity as the WT. Thus POPG acts as a diluent surface to which the
      lipase binds in an active, or "open", form for the catalytic turnover; however,
      the diluent molecules have poor affinity for the active site. Analysis of the
      substrate and the diluent concentration dependence of the rate of hydrolysis
      provides a basis for the determination of the primary interfacial catalytic
      parameters. As a competitive substrate, tributyrin provided a check for the
      apparent affinity parameters. Nonidealities from the fractional difference in the
      molecular areas in interfaces are expressed as the area correction factor and can
      be interpreted as a first-order approximation for the interfacial activity
      coefficient. The basis for the interfacial activation of tlTGL on anionic
      interface is attributed to cationic R81, R84, and K98 in the "hinge" around the
      86-93 "lid" segment of tlTGL.

PMID- 9578546
TI  - Structural coupling of troponin C and actomyosin in muscle fibers.
AB  - EPR of spin labeled TnC at Cys98 was used to explore the possible structural
      coupling between TnC in the thin filament and myosin trapped in the intermediate
      states of ATPase cycle. Weakly attached myosin heads (trapped by low ionic
      strength, low temperature and ATP) did not induce structural changes in TnC as
      compared to relaxed muscle, as spin labeled TnC displayed the same narrow
      orientational distribution [Li, H.-C., and Fajer, P. G. (1994) Biochemistry 33,
      14324]. Ca2+-binding alone resulted in disordering of the labeled domain of TnC.
      Additional conformational changes of TnC occurred upon the attachment of strongly
      bound, prepower stroke myosin heads (trapped by AlF4-). These changes were not
      present in ghost fibers which myosin had been removed, excluding direct effects
      of AlF4- on the orientation of TnC in muscle fibers. The postpower stroke heads
      (rigor.ADP/Ca2+ and rigor/Ca2+) induced further changes in the orientational
      distribution of labeled domain of TnC irrespective of the degree of cooperativity
      in thin filaments. We thus conclude that troponin C in thin filaments detects
      structural changes in myosin during force generation, implying that there is a
      structural coupling between actomyosin and TnC.

PMID- 9578547
TI  - Distances between the paclitaxel, colchicine, and exchangeable GTP binding sites
      on tubulin.
AB  - Distances between the paclitaxel, colchicine, and exchangeable GTP binding sites
      on tubulin polymers have been probed using fluorescence spectroscopy. Techniques
      for measuring fluorescence resonance energy transfer (FRET) between fluorescent
      or chromophoric ligands for each binding site were employed. 2-Debenzoyl-2-(m
      aminobenzoyl)paclitaxel (2-AB-PT) was the fluorophore ligand for the paclitaxel
      binding site; thiocolchicine, allocolchicine, and MDL 27048 were probes for the
      colchicine site, and 2'(or 3')-O-(trinitrophenyl)guanosine 5'-triphosphate (TNP
      GTP) was the fluorophore ligand for the exchangeable GTP site. The distance
      between the colchicine and paclitaxel binding sites was determined with two
      different acceptor ligands in the colchicine site. An average distance
      distribution of 17 A was found in both cases. Energy transfer between 2-AB-PT
      bound to the paclitaxel site and TNP-GTP (acceptor) bound to the exchangeable GTP
      site was observed in the polymer. The average distance distribution between the
      fluorophores was 16.0 A, but the half-width of the distribution was large (17.9
      A), which indicates that energy transfer between more than one donor-acceptor
      pair occurred in the system. One interpretation of this result is that 2-AB-PT
      serves as an energy transfer donor for two GTP sites, one contained on the same
      subunit and one on an adjacent protofilament. No FRET was observed between
      ligands bound to the colchicine and exchangeable GTP sites, indicating that the
      result of colchicine binding on the GTP region of beta-tubulin is a long range,
      allosteric effect. The results from these experiments are interpreted in terms of
      known structural features of microtubules.

PMID- 9578548
TI  - Novel natural product 5,5-trans-lactone inhibitors of human alpha-thrombin:
      mechanism of action and structural studies.
AB  - High-throughput screening of methanolic extracts from the leaves of the plant
      Lantana camara identified potent inhibitors of human alpha-thrombin, which were
      shown to be 5,5-trans-fused cyclic lactone euphane triterpenes [O'Neill et al.
      (1998) J. Nat. Prod. (submitted for publication)]. Proflavin displacement studies
      showed the inhibitors to bind at the active site of alpha-thrombin and alpha
      chymotrypsin. Kinetic analysis of alpha-thrombin showed tight-binding reversible
      competitive inhibition by both compounds, named GR133487 and GR133686, with
      respective kon values at pH 8.4 of 1.7 x 10(6) s-1 M-1 and 4.6 x 10(6) s-1 M-1.
      Electrospray ionization mass spectrometry of thrombin/inhibitor complexes showed
      the tight-bound species to be covalently attached, suggesting acyl-enzyme
      formation by reaction of the active-site Ser195 with the trans-lactone carbonyl.
      X-ray crystal structures of alpha-thrombin/GR133686 (3.0 A resolution) and alpha
      thrombin/GR133487 (2.2 A resolution) complexes showed continuous electron density
      between Ser195 and the ring-opened lactone carbonyl, demonstrating acyl-enzyme
      formation. Turnover of inhibitor by alpha-thrombin was negligible and mass
      spectrometry of isolated complexes showed that reversal of inhibition occurs by
      reformation of the trans-lactone from the acyl-enzyme. The catalytic triad
      appears undisrupted and the inhibitor carbonyl occupies the oxyanion hole,
      suggesting the observed lack of turnover is due to exclusion of water for
      deacylation. The acyl-enzyme inhibitor hydroxyl is properly positioned for
      nucleophilic attack on the ester carbonyl and therefore relactonization;
      furthermore, the higher resolution structure of alpha-thrombin/GR133487 shows
      this hydroxyl to be effectively superimposable with the recently proposed
      deacylating water for peptide substrate hydrolysis [Wilmouth, R. C., et al.
      (1997) Nat. Struct.Biol. 4, 456-462], suggesting the alpha-thrombin/GR133487
      complex may be a good model for this reaction.

PMID- 9578549
TI  - Identification of a model cardiac glycoside receptor: comparisons with Na+,K+
      ATPase.
AB  - The availability of high-affinity anti-digoxin monoclonal antibodies (mAbs)
      offers the potential for their use as models for the characterization of the
      relationship between receptor structure and cardiac glycoside binding. We have
      characterized the binding of anthroylouabain (AO), a fluorescent derivative of
      the cardiac glycoside ouabain, to mAbs 26-10, 45-20, and 40-50 [Mudgett-Hunter,
      M., et al. (1995) Mol. Immunol. 22, 477] and lamb kidney Na+, K+-ATPase by
      monitoring the resultant AO fluorescence emission spectra, anisotropy, lifetime
      values, and Forster resonance energy transfer (FRET) from protein tryptophan(s)
      (Trp) to AO. These data suggest that the structural environment in the vicinity
      of the AO-binding site of Na+,K+-ATPase is similar to that of mAb 26-10 but not
      mAbs 45-20 and 40-50. A model of AO complexed to the antigen binding fragment
      (Fab) of mAb 26-10 which was generated using known X-ray crystal structural data
      [Jeffrey, P. D., et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10310] shows a
      heavy chain Trp residue (Trp-H100) that is close ( approximately 3 A) to the
      anthroyl moiety. This is consistent with the energy transfer seen upon AO binding
      to mAb 26-10 and suggests that Trp-H100, which is part of the antibody's cardiac
      glycoside binding site, is a major determinant of the fluorescence properties of
      bound AO. In contrast, the generated model of AO complexed to Fab 40-50 [Jeffrey,
      P. D., et al. (1995) J. Mol. Biol. 248, 344] shows a heavy chain Tyr residue (Tyr
      H100) which is part of the cardiac glycoside binding site, located approximately
      10 A from the anthroyl moiety. The closest Trp residues (H52 and L35) are located
      approximately 17 A from the anthroyl moiety, and no FRET is observed despite the
      fact that these Trp residues are close enough for significant FRET to occur. The
      energy transfer seen upon AO binding to Na+,K+-ATPase suggests the presence of
      one completely quenched or two highly quenched enzyme Trp residues approximately
      10 and approximately 17 A, respectively, from the anthroyl moiety. These data
      suggest that the Na+,K+-ATPase Trp residue(s) involved in fluorescence energy
      transfer to AO is likely to be part of the cardiac glycoside binding site.

PMID- 9578550
TI  - Photo-cross-linking studies suggest a model for the architecture of an active
      human immunodeficiency virus type 1 integrase-DNA complex.
AB  - The virally encoded integrase protein carries out retroviral integration, which
      requires specific interactions with the two ends of the viral DNA, and also with
      host DNA that is the target of integration. We attached a photo-cross-linking
      agent to specific viral and target DNA sites to identify regions of the integrase
      polypeptide that are in close proximity to those substrate features in the active
      integrase-DNA complex. The active form of integrase is a multimer. The higher
      order organization of the active integration complex was therefore investigated
      by determining whether specific cross-links occurred to the active-site
      containing protomer. Both viral and target DNA cross-links to human
      immunodeficiency virus type 1 (HIV-1) integrase mapped predominantly to integrase
      protomers in trans to the active site, in a multimeric integrase complex. The
      results provide the basis for a model of the protein-DNA architecture of an
      active HIV-1 integration complex that suggests specific functions for the N
      terminal, core, and C-terminal domains of retroviral integrase. One implication
      of this model is that the integrase multimer that mediates concerted integration
      of the viral DNA ends is composed of at least eight integrase protomers.

PMID- 9578551
TI  - Probing the active site of cytochrome P450 2B1: metabolism of 7-alkoxycoumarins
      by the wild type and five site-directed mutants.
AB  - A series of 7-alkoxycoumarins (chain length of 1-7 carbon atoms) was utilized as
      active site probes of purified Escherichia coli-expressed cytochrome P450 2B1
      wild type and five site-directed mutants (I114V, F206L, V363A, V363L, and G478S).
      The production of 7-hydroxycoumarin, the O-dealkylation product, by the wild-type
      enzyme exhibited a rank order of C2 > C4 > C3 > C1 > C5 > C6 = C7. The pattern
      observed for the P450 I114V mutant was similar to that of the wild-type enzyme,
      whereas with F206L and G478S mutants, the rate of O-dealkylation was low with all
      the compounds. In contrast, with V363A, the highest rate of product formation was
      observed with 7-butoxycoumarin. The V363L mutant preferentially catalyzed the O
      dealkylation of 7-methoxy- and 7-ethoxycoumarin, and a further increase in the
      length of the alkyl chain led to a marked decrease in product formation. The
      stoichiometry of 7-butoxycoumarin oxidation by V363L suggested that products
      other than 7-hydroxycoumarin were also formed. HPLC and GC-EIMS analyses revealed
      that P450 2B1 V363L produced 7-(3-hydroxybutoxy)coumarin and 7-(4
      hydroxybutoxy)coumarin as major oxidation products, while the V363A mutant mainly
      catalyzed the O-dealkylation of 7-butoxycoumarin. Docking of alkoxycoumarins into
      the active site of a P450 2B1 homology model confirmed the importance of the
      studied residues in substrate dealkylation and explained the formation of novel 7
      butoxycoumarin products by the V363L mutant.

PMID- 9578552
TI  - Structure of the hexapeptide xenobiotic acetyltransferase from Pseudomonas
      aeruginosa.
AB  - The crystal structure of the xenobiotic acetyltransferase from Pseudomonas
      aeruginosa PA103 (PaXAT) has been determined, as well as that of its complex with
      the substrate chloramphenicol and the cofactor analogue desulfo-coenzyme A. PaXAT
      is a member of the large hexapeptide acyltransferase family of enzymes that
      display tandem repeated copies of a six-residue hexapeptide repeat sequence motif
      encoding a left-handed parallel beta helix (L betaH) structural domain. The
      xenobiotic acetyltransferase class of hexapeptide acyltransferases is composed of
      microbial enzymes that utilize acetyl-CoA to acylate a variety of hydroxyl
      bearing acceptors. The active site of trimeric PaXAT is a short tunnel into which
      chloramphenicol and the cofactor analogue desulfo-CoA project from opposite ends.
      This tunnel is formed by the flat parallel beta sheets of two separate L betaH
      domains and an extended 39-residue loop. His 79 of the extended loop forms
      hydrogen bonds from its imidazole NE2 atom to the 3-hydroxyl group of
      chloramphenicol and from its ND1 group to the peptide oxygen of Thr 86. The
      interactions of this histidine residue are similar to those found in the
      structurally unrelated type III chloramphenicol acetyltransferase and suggest
      that His 79 of PaXAT may be similarly positioned and tautomerically stabilized to
      serve as a general base catalyst.

PMID- 9578554
TI  - Differential intracellular signaling of the GalR1 and GalR2 galanin receptor
      subtypes.
AB  - The diverse physiological functions exerted by the neuropeptide galanin may be
      regulated by multiple G protein-coupled receptor subtypes and intracellular
      signaling pathways. Three galanin receptor subtypes (GalRs) have been recently
      cloned, but the G protein coupling profiles of these receptors are not completely
      understood. We have generated GalR1- and GalR2-expressing Chinese hamster ovary
      (CHO) cell lines and systematically examined the potential for these two
      receptors to couple to the Gs, Gi, Go, and Gq proteins. Galanin did not stimulate
      an increase in cAMP levels in GalR1/CHO or GalR2/CHO cells, suggesting an
      inability of either receptor to couple to Gs. Galanin inhibited forskolin
      stimulated cAMP production in GalR1/CHO cells by 70% and in GalR2/CHO cells by
      30%, suggesting a strong coupling of GalR1 to Gi and a more modest coupling
      between GalR2 and Gi. GalR1 and GalR2 both mediated pertussis toxin-sensitive
      MAPK activity (2-3-fold). The stimulation mediated by GalR1 was inhibited by
      expression of the C-terminus of beta-adrenergic receptor kinase (beta ARKct),
      which specifically inhibits G beta gamma signaling, but was not affected by the
      protein kinase C (PKC) inhibitor, bis[indolylmaleimide], or cellular depletion of
      PKC. In contrast, GalR2-mediated MAPK activation was not affected by beta ARKct
      expression but was abolished by inhibition of PKC activity. The data demonstrate
      that GalR1 is coupled to a Gibetagamma signaling pathway to mediate MAPK
      activation. In contrast, GalR2 utilizes a distinct signaling pathway to mediate
      MAPK activation, which is consistent with Go-mediated MAPK activation in CHO
      cells. Galanin was unable to stimulate inositol phosphate (IP) accumulation in
      CHO or COS-7 cells expressing GalR1. In contrast, galanin stimulated a 7-fold
      increase in IP production in CHO or COS-7 cells expressing GalR2. The GalR2
      mediated IP production was not affected by pertussis toxin, suggesting a linkage
      of GalR2 with Gq/G11. Thus, the GalR1 receptor appears to activate only the Gi
      pathway. By contrast, GalR2 is capable of stimulating signaling which is
      consistent with activation of Go, Gq/G11, and Gi. The differential signaling
      profiles and the tissue distribution patterns of GalR1 and GalR2 may underlie the
      functional spectra of galanin action mediated by these galanin receptors and
      regulate the diverse physiological functions of galanin.

PMID- 9578553
TI  - Interfacial recognition by bee venom phospholipase A2: insights into
      nonelectrostatic molecular determinants by charge reversal mutagenesis.
AB  - The basis for tight binding of bee venom phospholipase A2 (bvPLA2) to anionic
      versus zwitterionic phospholipid interfaces is explored by charge reversal
      mutagenesis of basic residues (lysines/arginines to glutamates) on the putative
      membrane binding surface. Single-site mutants and, surprisingly, multisite
      mutants (2-5 of the 6 basic residues mutated) are fully functional on anionic
      vesicles. Mutants bind tightly to anionic vesicles, and active-site substrate and
      Ca2+ binding are not impaired. Multisite mutants undergo intervesicle exchange
      slightly faster than wild type, especially in the presence of salt. It is
      estimated that electrostatic contribution to interfacial binding is modest,
      perhaps 2-3 kcal/mol of the estimated 15 kcal/mol. Elution properties of bvPLA2
      from HPLC columns containing solid phases of tightly packed monolayers of
      phosphocholine amphiphiles suggest that ionic effects provide a modest portion of
      the interfacial binding energy and that this contribution decreases as the number
      of cationic residues mutated is increased. These results are consistent with the
      observation that Gila monster venom PLA2 (Pa2), which is homologous to bvPLA2,
      has high activity on anionic vesicles despite the fact that it has only a single
      basic residue on its putative interfacial recognition face. Results with bvPLA2
      mutants show that manoalogue and 12-epi-scalaradial inactivate bvPLA2 by
      modification of K94. Also, deletion of the large beta-loop (residues 99-118) is
      without consequence for interfacial binding and catalysis of bvPLA2. All
      together, the preferential binding of bvPLA2 to anionic vesicles versus
      phosphatidylcholine vesicles is mainly due to factors other than electrostatics.
      Therefore hydrogen-bonding and hydrophobic interactions must provide a major
      portion of the interfacial binding energy, and this is consistent with recent
      spectroscopic studies.

PMID- 9578555
TI  - Phosphorylation destabilizes the amino-terminal domain of enzyme I of the
      Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system.
AB  - Thermal stabilities of enzyme I (63 562 M(r) subunit, in the Escherichia coli
      phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS), and a cloned
      amino-terminal domain of enzyme I (EIN; 28 346 Mr) were investigated by
      differential scanning calorimetry (DSC) and far-UV circular dichroism (CD) at pH
      7.5. EIN expressed in a delta pts E. coli strain showed a single, reversible, two
      state transition with Tm = 57 degrees C and an unfolding enthalpy of
      approximately 140 kcal/mol. In contrast, monomeric EIN expressed in a wild-type
      strain (pts+) had two endotherms with Tm congruent with 50 and 57 degrees C and
      overall delta H = 140 kcal/mol and was converted completely to the more stable
      form after five DSC scans from 10 to 75 degrees C (without changes in CD:
      approximately 58% alpha-helices). Thermal conversion to a more stable form was
      correlated with dephosphorylation of EIN by mass spectral analysis. Dephospho
      enzyme I (monomer right arrow over left arrow dimer) exhibited endotherms for C-
      and N-terminal domain unfolding with Tm = 41 and 54 degrees C, respectively.
      Thermal unfolding of the C-terminal domain occurred over a broad temperature
      range ( approximately 30-50 degrees C), was scan rate- and concentration
      dependent, coincident with a light scattering decrease and Trp residue exposure,
      and independent of phosphorylation. Reversible thermal unfolding of the
      nonphosphorylated N-terminal domain was more cooperative, occurring from 50 to 60
      degrees C. DSC of partially phosphorylated enzyme I indicated that the amino
      terminal domain was destabilized by phosphorylation (from Tm = 54 to
      approximately 48 degrees C). A decrease in conformational stability of the amino
      terminal domain of enzyme I produced by phosphorylation of the active-site His
      189 has the physiological consequence of promoting phosphotransfer to the
      phosphocarrier protein, HP(r).

PMID- 9578556
TI  - Nucleosome assembly on telomeric sequences.
AB  - The organization of telomeric chromatin differs from that of bulk chromatin in
      some peculiar features, such as the unusually short nucleosomal spacing found in
      vertebrates. Telomeric DNAs are straight, since they consist mostly of 6-8-bp
      repeated sequences, therefore out of phase with the B DNA period. This feature
      should be of relevance in nucleosome formation, suggesting the usefulness of
      studying simple model systems of nucleosome assembly. We reconstituted
      nucleosomes in vitro, by using purified histone octamers and/or by octamer
      transfer from chicken erythrocyte nucleosomes, onto telomeric sequences from
      human, Arabidopsis thaliana, and Saccharomyces cerevisiae. All of these telomeres
      contain GGG and GGT triplets but are characterized by different repeat lengths
      (6, 7, and 8 bp). The free energies involved in the association process are the
      highest among the biological sequences so far assayed, suggesting a main role of
      DNA flexibility in the assembly of telomeric chromatin. Digestion studies with
      DNase I, hydroxyl radicals, exonuclease III, and lambda exonuclease indicate that
      telomeric nucleosomes are characterized by multiple translational positioning
      without rotational phasing, whereas the telomeric DNA folding around the histone
      octamer shows the canonical periodicity of about 10.2 bp. The experimental
      results and a theoretical simulation of DNase I digestion indicate a multiple
      nucleosome positioning with the periodicity of telomeric DNA. This suggests a
      main role of local chemical recognition between telomeric sequences and the
      histone octamer in nucleosome assembly.

PMID- 9578557
TI  - Dictyostelium myosin 25-50K loop substitutions specifically affect ADP release
      rates.
AB  - While most of the sequence of myosin's motor domain is highly conserved among
      various organisms and tissue types, the junctions between the 25 and 50 kDa
      domains and the 50 and 20 kDa domains are strikingly divergent. The 50-20K loop
      is positioned to interact with actin, while the 25-50K loop is situated nearer
      the ATP binding site [Rayment, I., et al. (1993) Science 261, 50-58]. Chimeric
      studies of the 50-20K loop [Uyeda, T. Q.-P., et al. (1994) Nature 368, 567-569;
      Rovner, A. S., et al. (1995) J. Biol. Chem. 270 (51), 30260-30263] have shown
      that this loop affects actin activation of ATPase activity. Given the function of
      myosin as a molecular motor, it was proposed that the 25-50K loop might
      specifically alter ADP release [Spudich, J. A. (1994) Nature 374, 515-518]. Here
      we study the role of this loop by engineering chimeras containing the
      Dictyostelium myosin heavy chain with loops from two enzymatically diverse
      myosins, rabbit skeletal and Acanthamoeba. The chimeric myosins complement the
      myosin null phenotype in vivo, bind nucleotide normally, interact normally with
      actin, and display wild-type levels of actin-activated ATPase activity. However,
      the rate of ADP release from the myosins, normally the slowest step involved in
      motility, was changed in a manner that reflects the activity of the donor myosin.
      In summary, studies of Dictyostelium myosin heavy chain chimeras have shown that
      the 50-20K sequence specifically affects the actin-activated ATPase activity
      [Uyeda, T. Q.-P., et al. (1994)] while the 25-50K sequence helps determine the
      rate of ADP release.

PMID- 9578558
TI  - Unfolding and refolding of cardiotoxin III elucidated by reversible conversion of
      the native and scrambled species.
AB  - Cardiotoxin analogue III (CTX III) isolated from the venom of the Taiwan Cobra
      (Naja naja atra) is a small molecular weight, all beta-sheet protein, cross
      linked by four disulfide bridges. The unfolding and refolding mechanisms of CTX
      III have been examined by monitoring the reversible conversion of the native and
      scrambled species. It is found that, in the presence of a denaturant
      (urea/guanidinium hydrochloride) and a thiol catalyst, CTX III forms a mixture of
      scrambled species by shuffling its four native disulfide bonds. Complete
      unfolding of CTX III can be achieved using either 3.0-4.0 M guanidinium
      hydrochloride (GdmCl) or 5.0-6.0 M urea. It is observed that GdmCl is
      thermodynamically more potent but kinetically less efficient than urea in
      unfolding CTX III. The rate constants of unfolding of CTX III in 8 M urea are
      significantly greater than that obtained in 5.0 M GdmCl and 8.0 M GdmCl.
      Interestingly, upon removal of the denaturant, scrambled species of CTX III is
      found to refold spontaneously through dynamic reshuffling of the non-native
      disulfides to attain the native disulfide linkages. In addition, CTX III contains
      highly reactive lysines which are modified by trace amounts of cyanate
      contaminant which exists invariably even in high-grade urea solutions. The
      reactive lysines of CTX III are modified by cyanate both in the native and
      unfolded states of the protein. The modification is nonselective, and the
      modified product is found to consist of highly heterogeneous species.
      Surprisingly, these heterogeneous species of modified CTX III are observed to
      display stability and folding/unfolding properties indistinguishable from those
      of the native CTX III. The knowledge obtained from the present study, on the
      conditions to convert the scrambled species, could provide useful clues for a
      rational design for snake venom cardiotoxins with potential therapeutic
      applications.

PMID- 9578559
TI  - Structural and functional consequences of haloenol lactone inactivation of murine
      and human glutathione S-transferase.
AB  - Mass spectrometric analysis of proteolysis products of haloenol lactone-modified
      glutathione S-transferase isozyme mGSTP1 indicates that the haloenol lactone 3
      cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone is covalently attached to the
      protein at Cys-47. Comparisons of the extent of adduct formation with losses in
      enzymatic activity indicate that mGSTP1 exhibits greatest reactivity toward the
      haloenol lactone, followed by mGSTM1 and mGSTA3. Activities of mGSTP1 and mGSTM1
      decrease in inverse proportion to haloenol lactone concentration, whereas
      modification had no apparent effect on catalytic activity of mGSTA3. Decreases in
      activity agree with the extent of protein modification observed in ESI mass
      spectra for mGSTP1 and mGSTM1 but not for mGSTA3. Kinetic studies employing
      recombinant human proteins with replacement of cysteine by serine at Cys-47 and
      Cys-101 indicate that rapid inactivation (t1/2 = 2 min) occurs only when residue
      47 is cysteine. Mass spectra of C47S-hGSTP1 incubated with haloenol lactone
      demonstrate covalent attachment of a haloenol lactone-glutathione conjugate and
      suggest that an ester forms between the lactone and Ser-47. Therefore, we propose
      that initial opening of the lactone ring is promoted by Cys-47 through thioester
      formation between the lactone carbonyl and the Cys-47 sulfhydryl. Enol-keto
      tautomerization and enzyme-mediated hydrolytic cleavage of the thioester produces
      a reactive alpha-bromoketone which reacts a second time with Cys-47 and
      inactivates the enzyme. These results suggest that Pi class GSTs have
      thioesterase activity and that haloenol lactone inactivation occurs through an
      enzyme-mediated process.

PMID- 9578560
TI  - Catalytic contribution of phenylalanine-101 of 3-oxo-Delta 5-steroid isomerase.
AB  - 3-Oxo-delta 5-steroid isomerase (KSI, EC 5.3.3.1) from Pseudomonas testosteroni
      catalyzes the isomerization of a variety of 3-oxo-delta 5-steroids to their
      conjugated Delta4-isomers through the formation of an intermediate dienolate ion.
      It has previously been found in our laboratory that the aromatic ring of Phe-101
      is important for catalysis. The present work extends these studies. Two double
      mutant KSIs (D38E/F101L and D38E/F101A) were prepared to compare the free energy
      profiles for the reactions catalyzed by these mutants and by D38E. Both double
      mutant KSIs show reduced values of kcat at pH 7 compared to D38E ( approximately
      25-fold for D38E/F101L and approximately 200-fold for D38E/F101A), similar to the
      reduced values for F101L and F101A relative to KSI ( approximately 30-fold for
      F101L and approximately 270-fold for F101A). Free energy profiles for the
      reactions catalyzed by D38E/F101L and D38E/F101A indicate that the bound
      transition state(s) and bound intermediate are destabilized when the large
      aromatic residue Phe-101 in D38E KSI is replaced by the smaller residues Leu or
      Ala. The pH-rate profiles for D38E, D38E/F101L, and D38E/F101A in the pH range
      3.9-8.7 show that the pKa of the catalytic base (Glu-38) is perturbed. In
      addition, these mutants have significant catalytic activity in the low-pH region.

PMID- 9578561
TI  - pH-linked binding of Mn(II) to manganese peroxidase.
AB  - The stability of Mn(II) binding to manganese peroxidase (MnP) has been studied as
      a function of pH by spectrophotometric and potentiometric titrations. The
      sensitivity of the potentiometric titrations allows collection of data that are
      consistent with a high-affinity and a low-affinity Mn(II) binding site on the
      peroxidase. The two sites differ in affinity by 4 to 900-fold between pH 4 and
      6.5. The stability of Mn(II) binding to the high-affinity site increases with
      increasing pH, while the stability of Mn(II) binding to the low-affinity site
      decreases with increasing pH. Interestingly, at pH values above 5.0, the high
      affinity site appears to be partially unavailable for binding Mn(II). A pH
      dependent structural change in the Mn(II) binding site is proposed to account for
      this partial inactivation at elevated pH.

PMID- 9578562
TI  - Equilibrium and kinetic folding of pigeon lysozyme.
AB  - In the present study, the search for a possible intermediate state in pigeon
      lysozyme is addressed by equilibrium and kinetic experiments using static and
      stopped-flow fluorescence and circular dichroism spectroscopies. In equilibrium
      conditions at pH 7.5, pigeon lysozyme shows no populated intermediate state in
      temperature- and GdnHCl-induced unfolding experiments. In the unfolding process
      at low pH, however, a distinct intermediate state with molten globule
      characteristics is observed. Ca2+ binding to the protein is found to stabilize
      the native state. The early folding intermediate observed in kinetic experiments
      corresponds to the equilibrium intermediate in that an important amount of
      secondary structure has already been established. Full accomplishment of native
      tertiary contacts is achieved in a fast exponential process with a rate constant
      (0.23-135 s-1) that is strongly dependent on refolding conditions. Binding
      experiments with the fluorescent inhibitor MeU-diNAG support these conclusions.
      The folding rate is not influenced by Ca2+ binding. Analysis of the refolding and
      unfolding kinetics determined as a function of denaturant concentration leads to
      a Gibbs energy profile with a rate-determining transition state between the N-
      and I-states. Comparison with previous results on the folding of hen egg white
      lysozyme emphasizes the crucial role of Trp 62 in stabilizing non-native
      interactions. The replacement of this residue by Tyr in pigeon lysozyme
      contributes to the formation of native tertiary contacts.

PMID- 9578564
TI  - Unanticipated inhibition of the metallo-beta-lactamase from Bacteroides fragilis
      by 4-morpholineethanesulfonic acid (MES): a crystallographic study at 1.85-A
      resolution.
AB  - As part of a structure-aided effort to design clinically useful inhibitors of
      metallo-beta-lactamases, the X-ray crystal structure of a complex between the
      metallo-beta-lactamase from Bacteroides fragilis and 4-morpholinoethanesulfonic
      acid (MES) has been determined and a model for the structure has been refined to
      a crystallographic R-factor of 0.151 for data between 10.0- and 1.85-A
      resolution. Although the binding of MES was an adventitious result of the use of
      MES as a buffer in the crystallization mixture, MES was subsequently shown to be
      a competitive inhibitor of the enzyme, with a Ki of 23 +/- 5 mM. MES binds in the
      same fashion to both of the molecules in the crystallographic asymmetric unit;
      both direct and solvent-mediated hydrogen bonds to the protein and to the
      binuclear zinc cluster are observed, involving the oxygens of the sulfonic acid
      group and the nitrogen of the morpholino ring. In addition, there are hydrophobic
      interactions between the morpholino ring and residues in the flexible beta-strand
      of the enzyme between residues 26 and 36. Comparison of this structure with the
      previously reported unliganded structures of the same enzyme [Concha, N. O.,
      Rasmussen, B. A., Bush, K., and Herzberg, O. (1996) Structure 4, 823-836; Carfi,
      A., Duee, E., Paul-Soto, R., Galleni, M., Frere, J. -M., and Dideberg, O. (1998)
      Acta Crystallogr. D54, 47-57] reveals that although the overall conservation of
      structure in the three different crystal lattices is very high, binding of MES is
      correlated with a significant change in the conformation of this beta-strand. The
      flexibility of this beta-strand will be an important consideration in the design
      of inhibitors of the metallo-beta-lactamases.

PMID- 9578563
TI  - Expression and characterization of four recombinant human dihydrodiol
      dehydrogenase isoforms: oxidation of trans-7, 8-dihydroxy-7,8
      dihydrobenzo[a]pyrene to the activated o-quinone metabolite benzo[a]pyrene-7,8
      dione.
AB  - The bioactivation of polycyclic aromatic hydrocarbons (PAHs) to their ultimate
      carcinogenic forms proceeds via the formation of proximate carcinogen trans
      dihydrodiols. Previous studies demonstrated that rat liver 3 alpha-hydroxysteroid
      dehydrogenase/dihydrodiol dehydrogenase (3 alpha-HSD/DD), a member of the aldo
      keto reductase (AKR) superfamily, oxidizes PAH trans-dihydrodiols to redox
      cycling o-quinones. Multiple closely related AKRs exist in human liver; however,
      it is unclear which, if any, participate in PAH activation by catalyzing the
      NADP+ -dependent oxidation of PAH trans-dihydrodiols. In this study, cDNAs
      encoding four human DD isoforms were isolated from HepG2 cells using isoform
      selective RT-PCR. The recombinant proteins were overexpressed in Escherichia
      coli, purified to homogeneity, and kinetically characterized. Calculation of KM
      and kcat values of each isoform for model substrates revealed that they possessed
      enzymatic activities assigned to native human liver DD1, DD2, DD4, and type 2
      3alpha-HSD (DDX) proteins. The ability of human DDs to oxidize the potent
      proximate carcinogen (+/-)-trans-7,8-dihydroxy-7, 8-dihydrobenzo[a]pyrene (BP
      diol) was then examined. A reverse phase HPLC radiochemical assay demonstrated
      that all four isoforms oxidize (+/-)-BP-diol in the following rank order: DD2 >
      DD1 > DD4 > DDX. Each DD consumed the entire racemic BP-diol mixture, indicating
      that both the minor (+)-S,S- and major (-)-R,R-stereoisomers formed in vivo are
      substrates. First-order decay plots showed that DD1 and DD2 displayed preferences
      for one of the stereoisomers, and circular dichroism spectroscopy indicated that
      this isomer was the (+)-7S, 8S-enantiomer. The products of these reactions were
      trapped as either glycine or thiol ether conjugates of benzo[a]pyrene-7,8-dione
      (BPQ), indicating that the initial oxidation product was the reactive BPQ. Thus,
      human liver possesses multiple AKRs which contribute to PAH activation by
      catalyzing the NADP+-dependent oxidation of PAH trans-dihydrodiols to redox
      active o-quinones.

PMID- 9578565
TI  - Kinetic and calcium-binding properties of three calcium-dependent protein kinase
      isoenzymes from soybean.
AB  - Calmodulin-like domain protein kinases (CDPKs) are a family of calcium- but not
      calmodulin-dependent protein kinases found in a wide variety of plants and in
      protists. CDPKs are encoded by large multigene families, and to assess whether
      family members play distinct or redundant roles in vivo, we characterized soybean
      CDPK isoforms alpha, beta, and gamma, which share 60-80% identity in amino acid
      sequence. RNA blot analysis showed that the three CDPKs were expressed in most
      plant tissues examined and in suspension-cultured soybean cells. Recombinant
      CDPKalpha, -beta, and -gamma phosphorylated peptide substrates containing the
      four-residue motif R/K-X-X-S/T, but CDPKalpha was the most selective for residues
      outside of the motif. The CDPKs were inhibited by the general protein kinase
      inhibitors K252a and staurosporine and by calphostin C, which is an inhibitor of
      protein kinase C. The calcium-binding properties of each CDPK were distinct. The
      Kd's for Ca2+ determined by flow dialysis in the absence of substrates were 51,
      1.4, and 1.6 micro M for CDPKalpha, -beta, and -gamma, respectively. In the
      presence of the peptide substrate syntide-2 the Kd of CDPKalpha decreased to 0.6
      microM. Also, the sensitivity of this isoenzyme's activity to calcium varied with
      protein substrate. The concentrations of Ca2+ required for half-maximal activity
      (K0.5) for each CDPK with syntide-2 as substrate were 0.06, 0.4, and 1 micro M,
      respectively. These results show that members of the CDPK family differ in
      biochemical properties and support the hypothesis that each isoform may have a
      distinct role in calcium signal transduction.

PMID- 9578566
TI  - Reconstitution of membrane-integrated quinoprotein glucose dehydrogenase
      apoenzyme with PQQ and the holoenzyme's mechanism of action.
AB  - Membrane-integrated quinoprotein glucose dehydrogenase from Acinetobacter
      calcoaceticus was produced by heterologous expression of the gene for it in an
      Escherichia coli recombinant strain. The apoenzyme (lacking the cofactor
      pyrroloquinoline quinone, PQQ) was solubilized with Triton X-100 and purified to
      homogeneity. Reconstitution of the apoenzyme to full activity in the assay was
      achieved with a stoichiometric amount of PQQ in the presence of Mg2+. Just as for
      other PQQ-containing dehydrogenases where Ca2+ fulfills this role, Mg2+ anchors
      PQQ to the mGDH protein and activates the bound cofactor. This occurs in a
      precise way since high anomer specificity was found for the enzyme toward the
      sugars tested. Although the steady-state-type kinetics were as expected for a dye
      linked dehydrogenase (ping-pong) and the PQQ in it was present in oxidized form,
      addition of glucose to the holoenzyme resulted in a very slow but continuous
      production of gluconolactone; i.e., the reaction did not stop after one turnover,
      with O2 apparently acting as an (albeit poor) electron acceptor by reoxidizing
      PQQH2 in the enzyme. The surprisingly low reactivity with glucose, in the absence
      of dye, as compared to the activity observed in the steady-state assay appeared
      to be due to formation of an anomalous enzyme form, mGDH. Formation of normal
      holoenzyme, mGDH, reducing added glucose immediately to gluconolactone (in one
      turnover), was achieved by treating mGDH with sulfite, by reconstituting
      apoenzyme with PQQ in the presence of sulfite, or by applying assay conditions to
      mGDH (addition of PMS/DCPIP). As compared to other quinoprotein dehydrogenases,
      mGDH appears to be unique with respect to the mode of PQQ-binding, as expressed
      by the special conditions for reconstitution and the absorption spectra of the
      bound cofactor, and the reactivity of the reduced enzyme toward O2. The primary
      cause for this seems not to be related to a different preference for the
      activating bivalent metal ion but to the special way of binding of PQQ to mGDH.

PMID- 9578567
TI  - Structural heterogeneity and ligand binding in carbonmonoxy myoglobin crystals at
      cryogenic temperatures.
AB  - We have characterized the ligand-rebinding behavior of single crystal native
      sperm whale carbonmonoxy myoglobin (swMbCO) (space group P21) and a synthetic
      mutant swMbCO (space group P6) at cryogenic temperatures by using temperature
      derivative spectroscopy (TDS) with monitoring of the CO stretch bands in the mid
      infrared. Crystals were studied at pH 5.1 and 7.0 for native swMbCO and at pH 7.0
      for the mutant; both short-flash and extended illumination protocols were
      performed. The TDS analysis yields the enthalpy barrier distributions for
      recombination in the individual taxonomic (A) substates, A0, A1, and A3. A single
      gaussian barrier distribution gave a good first-order description but was
      insufficient to precisely fit the data within each substate. An additional
      minority species was necessary to model the enhanced rebinding below 30 K, which
      likely appears because of quantum tunneling. The peak positions and widths of the
      enthalpy distributions are similar for the P21 and P6 crystal forms, indicating
      that crystal-packing forces have only very minor effects on the structure at the
      active site. Moreover, the widths of the (dominant) distributions are
      qualitatively similar to those observed with glycerol-water solutions, which
      shows that the degree of structural heterogeneity is similar for solution and
      crystalline samples. For the A3 substate, a significantly lower peak enthalpy was
      obtained (by approximately 4 kJ/mol) than for solutions, while the peak shifts in
      the A0 and A1 substates were small. In samples cooled under illumination,
      discrete populations with higher rebinding barriers were observed. Concomitant
      changes in the stretch absorption of the photodissociated CO (B states) only
      occur between 100 and 130 K. They likely arise from movements of the ligand in
      the heme pocket between discrete sites.

PMID- 9578568
TI  - Unique DNA binding mode of the N-terminal zinc finger of transcription factor
      Sp1.
AB  - Transcription factor Sp1 has three tandem repeats of a Cys2His2-type zinc finger
      motif and specifically binds to GC box DNA. Although the DNA binding mode of the
      three zinc fingers of Sp1 is predicted to be similar to that of Zif268, this
      model does not explain the DNA binding property of the N-terminal zinc finger
      (finger 1). To understand the DNA recognition mode of Sp1, we have performed
      detailed analyses for the contribution of finger 1 to the high-affinity binding
      to the GC box DNA and for the interaction mechanism between finger 1 and DNA.
      Results of electrophoretic analyses using finger-deleted mutants of Sp1 and GC
      box mutants in the finger-contacting subsite demonstrate that the contribution of
      finger 1 to the total DNA binding affinity is lower than that of the C-terminal
      finger 3 but is dispensable for the high-affinity binding. The DNA sequence
      selectivity of finger 1 at the 3'-portion of the GC box is lower than that of
      fingers 2 and 3 at the 5'-portion. Alanine scanning mutagenesis in the alpha
      helix of finger 1 reveals that Lys-1 immediately preceding the helix is important
      for the recognition of the two guanine bases, but other putative key amino acids
      do not affect the DNA binding. These results demonstrate that (1) the
      contribution of finger 1 to the DNA binding affinity and the sequence selectivity
      of Sp1 is smaller than that of fingers 2 and 3 and (2) the interaction mechanism
      between finger 1 and DNA is different from the Zif268 model. DNA interaction of
      Sp1 finger 1 has also been discussed in connection with that of TFIIIA or WT1.

PMID- 9578569
TI  - The amino acid following an asn-X-Ser/Thr sequon is an important determinant of N
      linked core glycosylation efficiency.
AB  - Many eukaryotic proteins are modified by Asn-linked (N-linked) glycosylation. The
      number and position of oligosaccharides added to a protein by the enzyme
      oligosaccharyltransferase can influence its expression and function. N-Linked
      glycosylation usually occurs at Asn residues in Asn-X-Ser/Thr sequons where X not
      equal Pro. However, many Asn-X-Ser/Thr sequons are not glycosylated or are
      glycosylated inefficiently. Inefficient glycosylation at one or more Asn-X
      Ser/Thr sequons in a protein results in the production of heterogeneous
      glycoprotein products. These glycoforms may differ from one another in their
      level of expression, stability, antigenicity, or function. The signals which
      control the efficiency of N-linked glycosylation at individual Asn residues have
      not been fully defined. In this report, we use a site-directed mutagenesis
      approach to investigate the influence of the amino acid at the position following
      a sequon (the Y position, Asn-X-Ser/Thr-Y). Variants of rabies virus glycoprotein
      containing a single Asn-X-Ser/Thr sequon at Asn37 were generated. Variants were
      designed with each of the twenty common amino acids at the Y position, with
      either Ser or Thr at the hydroxy (Ser/Thr) position. The core glycosylation
      efficiency of each variant was quantified using a cell-free
      translation/glycosylation system. These studies reveal that the amino acid at the
      Y position is an important determinant of core glycosylation efficiency.

PMID- 9578570
TI  - The gene for human protein Z is localized to chromosome 13 at band q34 and is
      coded by eight regular exons and one alternative exon.
AB  - Human protein Z is a vitamin K-dependent plasma glycoprotein, deficiency of which
      leads to a mild bleeding tendency. Protein Z appears to assist hemostasis by
      binding thrombin and promoting its association with phospholipid vesicles. In
      this study, to characterize the gene for protein Z, its organization and
      structure were determined by a combination of PCR amplification of leukocyte DNA
      and isolation of phage clones from a human genomic library. The gene spanned
      about 14 kb and consisted of 9 exons including one alternative exon. It was of
      note that the gene organization was essentially identical to that of other
      vitamin K-dependent proteins, such as factors VII, IX, and X and protein C. The
      nucleotides in introns at exon/intron boundaries for eight regular exons were the
      consensus GT-AG sequences. In contrast, the sequence at an optional exon/intron
      junction was found to be GC rather than GT. The extra exon inserts a unique
      peptide consisting of 22 amino acids in the prepro-leader sequence. A similar
      situation was previously observed in factor VII, but not in other vitamin K
      dependent plasma proteins. We also assigned the gene for protein Z to chromosome
      13 by PCR amplification of genomic DNAs from human/hamster cell hybrids.
      Fluorescence in situ hybridization, employing a genomic clone coding for human
      protein Z, further localized the gene to band q34, where the genes of three other
      vitamin K-dependent proteins are clustered. These genes may have evolved via
      duplication of an ancestral gene at this locus.

PMID- 9578571
TI  - Structural features that determine the enzymatic potency and specificity of human
      angiogenin: threonine-80 and residues 58-70 and 116-123.
AB  - Human angiogenin (Ang), a homologue of bovine pancreatic ribonuclease A (RNase
      A), is a potent inducer of blood vessel formation. It exerts a ribonucleolytic
      activity that is 10(5)-10(6)-fold lower than that of RNase A but nonetheless
      essential for biological action. Previous studies revealed some of the structural
      features of Ang that underlie its catalytic inefficiency: Gln-117 blocks the
      space corresponding to the pyrimidine binding site of RNase A and Ang lacks the
      disulfide loop 65-72 that forms most of the purine binding site of RNase A.
      Additional features have now been identified by mutagenesis and kinetics. Thr-80,
      which hydrogen-bonds to the pyrimidine-binding residue Thr-44, plays an important
      part in attenuating activity and in determining pyrimidine specificity: mutation
      to Ala increases activity toward cytidylyl substrates by 11-15-fold but has only
      a minimal effect on cleavage of uridylyl substrates. The properties of T44A/T80A
      and Q117A/T80A double mutants demonstrate that these changes are mediated by Thr
      44 and are largely independent of the blockage by Gln-117. The side chain of Ser
      118 also suppresses enzymatic activity: S118A is 5-7-fold more effective than
      Ang. This increase appears to reflect the loss of a hydrogen bond with Asp-116
      that helps to orient Gln-117. The effects of deleting residues 119-123 suggest
      that main-chain atoms of the C-terminal 3(10) helix make a small further
      contribution. Finally, the significance of the absence of the RNase A loop 65-72
      from Ang has been investigated by reexamining the earlier derivative ARH-I (in
      which Ang residues 58-70 have been replaced by residues 59-73 of RNase) and
      generating new derivatives of this hybrid protein. The results suggest that the
      RNase A segment of ARH-I not only provides more effective purine recognition but
      also counteracts the deleterious effects of Gln-117 and Thr-80 on the pyrimidine
      site.

PMID- 9578572
TI  - Inhibition of human angiogenin by DNA aptamers: nuclear colocalization of an
      angiogenin-inhibitor complex.
AB  - Specific ligands (aptamers) for angiogenin were selected from a 72-mer
      oligodeoxynucleotide library consisting of 28 randomized positions flanked by two
      constant regions of 22 residues each. From a starting pool of approximately
      10(14) molecules, 19 angiogenin-binding ligands were obtained. Among them, two
      oligonucleotides showed significant inhibition of the ribonucleolytic activity of
      angiogenin with apparent Kis of 0.65 and 0.60 micro M, respectively. One of them
      was shortened on the basis of its secondary structure to provide a 45-mer
      oligonucleotide that retained much of the inhibitory properties of the parent
      molecule. It inhibits both the angiogenic and cell proliferative activities of
      angiogenin but does not interfere with its nuclear translocation in human
      endothelial cells. Importantly, the inhibitor is cotranslocated to the nucleus
      with angiogenin in a approximately 1:1 stoichiometric ratio. These results
      demonstrate that the inhibition of angiogenin-induced cell proliferation and
      angiogenesis by the oligonucleotide is due to suppression of the ribonucleolytic
      activity of angiogenin, an event that occurs most likely within the cell nucleus.

PMID- 9578573
TI  - Human neutrophils employ myeloperoxidase to convert alpha-amino acids to a
      battery of reactive aldehydes: a pathway for aldehyde generation at sites of
      inflammation.
AB  - We have recently demonstrated that activated phagocytes employ the heme protein
      myeloperoxidase, H2O2, and Cl- to oxidize the aromatic amino acid l-tyrosine to
      the reactive aldehyde p-hydroxyphenylacetaldehyde. We now present evidence for
      the generality of this reaction by demonstrating that neutrophils employ the
      myeloperoxidase-H2O2-Cl- system to oxidize nearly all of the common alpha-amino
      acids to yield a family of reactive aldehydes. Chemical characterization
      suggested that reactive carbonyl moieties were generated during amino acid
      oxidation by myeloperoxidase. The structures of amino-acid-derived aldehydes were
      confirmed using a variety of mass spectrometric methods. Aldehyde production
      required myeloperoxidase, H2O2, Cl-, and an amino acid; it was inhibited by heme
      poisons and catalase. Hypochlorous acid was the apparent oxidizing intermediate
      because its addition to alpha-amino acids resulted in the formation of the
      anticipated aldehyde. Stimulated human neutrophils likewise generated aldehydes
      from all classes of alpha-amino acids by a pathway inhibited by heme poisons and
      catalase, implicating myeloperoxidase and H2O2 in the cell-mediated reaction.
      Aldehyde production accounted for a significant fraction of the H2O2 generated by
      stimulated neutrophils at physiological concentrations of amino acids.
      Collectively, these results suggest that amino-acid-derived aldehydes represent a
      product of reactive oxidant species generated by activated phagocytes.

PMID- 9578574
TI  - Effects of copper on the structure and function of factor VIII subunits: evidence
      for an auxiliary role for copper ions in cofactor activity.
AB  - Factor VIII, a divalent metal ion-dependent heterodimer, contains a single copper
      atom, but the role of this metal in the structure and function of the cofactor is
      unclear. Earlier results showed that the dissociated heavy and light chains of
      factor VIII could be recombined in the presence of Ca(II) or Mn(II) but not
      Cu(II) to yield functional protein [Fay, P. J. (1988) Arch. Biochem. Biophys.
      262, 525-531]. Inclusion of Cu(I) or Cu(II) inhibited the Mn(II)- or Ca(II)
      dependent reconstitution of factor VIII with an IC50 approximately 10 micro M.
      The heavy chain was the susceptible subunit with inhibition by copper ion
      resulting from its reduced affinity for light chain. On the other hand, Mn(II)
      dependent factor VIII reconstitutions performed with Cu(II) light chain and
      native heavy chain occurred at an accelerated rate (approximately 10-fold) and
      yielded an enhanced activity ( approximately 50%), likely reflecting an increased
      specific activity of the heterodimer. Cu ions enhanced the activity of EDTA
      treated factor VIII in the presence of Ca(II) but not in its absence, suggesting
      that EDTA-treated factor VIII is not equivalent to separated subunits and that
      copper ions are auxiliary to ions that mediate reconstitution. Conformational
      analyses showed that the ellipticities and extrinsic fluorescence of both
      subunits were differentially affected by Cu(II) and Mn(II). These structural
      effects were fully reversed by EDTA. The metal ions had little if any effect on
      the conformation of intact factor VIII or the A1/A3-C1-C2 dimer. Mn(II) and
      Cu(II) stabilized the factor VIII light chain, and the latter stabilized the A1
      subunit derived from the heavy chain, yielding similar thermal denaturation
      profiles that were distinct from that observed for the Ca(II)-stabilized
      subunits. Thus both subunits of factor VIII bind copper ions, and the effects of
      this binding differ from the interactions observed with Ca(II) or Mn(II). These
      data support a model where copper in factor VIII likely functions to increase
      specific activity of the heterodimer rather than directly mediating the
      intersubunit interaction.

PMID- 9578575
TI  - Synthetic interface peptides as inactivators of multimeric enzymes: inhibitory
      and conformational properties of three fragments from Lactobacillus casei
      thymidylate synthase.
AB  - Three synthetic peptides corresponding to distinct segments of the subunit
      interface of the dimeric enzyme thymidylate synthase (residues 17-38, N 22;
      residues 174-190, M 17; and residues 201-220, C 20) have been investigated for
      their ability to function as inhibitors by modifying the quaternary structure of
      the enzyme. A dramatic reduction of enzyme activity is observed following
      incubation of TS with the C 20 peptide. The N 22 and M 17 peptides were unable to
      cause any loss of enzymatic activity. Addition of the C 20 peptide results in a
      loss of fluorescence of TS labeled with a dansyl group at Cys 198, following
      aggregation and precipitation of the protein. The effects are not observed for
      the N 22 or M 17 peptides. Loss of enzymatic activity is related to the ability
      of C 20 to promote protein aggregation. The conformations of the peptides have
      been studied using CD and NMR in order to correlate the observed function with
      solution structures. Peptides N 22 and M 17 are largely unstructured in aqueous
      solution. A population of nascent helical structures or multiple turn
      conformations has been detected for the C 20 peptide in aqueous solution by NMR.
      Addition of 50% (v/v) hexafluoroacetone trihydrate (HFA), a structure-stabilizing
      cosolvent, stabilizes the helical conformation in the C 20 peptide. Under similar
      conditions, N 22 and M 17 remain largely extended with observations of local beta
      turn conformations. Interestingly, the C 20 peptide is a beta-hairpin in the
      native structure, whereas the other two peptides are individual strand components
      of a beta-sheet.

PMID- 9578576
TI  - Dual inhibition of human type 4 phosphodiesterase isostates by (R, R)-(+/-)
      methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3- methyl-1
      pyrrolidinecarboxylate.
AB  - Purified recombinant human type 4 phosphodiesterase B2B (HSPDE4B2B) exists in
      both a low- and a high-affinity state that bind (R)-rolipram with Kd's of ca. 500
      and 1 nM, respectively [Rocque, W. J., Tian, G., Wiseman, J. S., Holmes, W. D.,
      Thompson, I. Z., Willard, D. H., Patel, I. R., Wisely, G. B., Clay, W. C.,
      Kadwell, S. H., Hoffman, C. R., and Luther, M. A. (1997) Biochemistry 36, 14250
      14261]. Since the tissue distribution of the two isostates may be significantly
      different, development of inhibitors that effectively inhibit both forms may be
      advantageous pharmacologically. In this study, enzyme inhibition and binding of
      HSPDE4B2B by (R, R)-(+/-)-methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]
      3-methyl-1-pyrrolidin ecarboxylate (1), a novel inhibitor of phosphodiesterase 4
      (PDE 4), were investigated. Binding experiments demonstrated high-affinity
      binding of 1 to HSPDE4B2B with a stoichiometry of 1:1. Inhibition of PDE activity
      showed only a single transition with an observed Ki similar to the apparent Kd
      determined by the binding experiments. Deletional mutants of HSPDE4B2B, which
      have been shown to bind (R)-rolipram with low affinity, were shown to interact
      with 1 with high affinity, indistinguishable from the results obtained with the
      full-length enzyme. Bound 1 was completely displaced by (R)-rolipram, and the
      displacement showed a biphasic transition that resembles the biphasic inhibition
      of HSPDE4B2B by (R)-rolipram. Theoretical analysis of the two transitions
      exemplified in the interaction of (R)-rolipram with HSPDE4B2B indicated that the
      two isostates were nonexchangeable. Phosphorylation at serines 487 and 489 on
      HSPDE4B2B had no effect on the stoichiometry of binding, the affinity for
      binding, or the inhibition of the enzyme by 1. These data further illustrate the
      presence of two isostates in PDE 4 as shown previously for (R)-rolipram binding
      and inhibition. In contrast to (R)-rolipram, where only one of the two isostates
      of PDE 4 binds with high affinity, 1 is a potent, dual inhibitor of both of the
      isostates of PDE 4. Kinetic and thermodynamic models describing the interactions
      between the nonexchangeable isostates of PDE 4 and its ligands are discussed.

PMID- 9578577
TI  - Human protoporphyrinogen oxidase: relation between the herbicide binding site and
      the flavin cofactor.
AB  - Protoporphyrinogen IX oxidase (protox) catalyzes the oxidation of
      protoporphyrinogen IX to protoporphyrin IX in the penultimate step of heme and
      chlorophyll biosynthesis in animals and plants. Protox is the target of light
      dependent peroxidizing herbicides and is inhibited at nanomolar levels by several
      chemical classes including tetrahydrophthalimides (discussed below) and diphenyl
      ethers (e.g., acifluorfen) usually with little selectivity between the mammalian
      and plant enzymes. The herbicide binding site is examined here with a
      photoaffinity radioligand optimized on the basis of structure-activity
      relationships. A radiosynthetic procedure is described for this new herbicidal
      probe, N-(5-azido-4-chloro-2-fluorophenyl)-3,4,5, 6-[3H]tetrahydrophthalimide
      ([3H]AzTHP), resulting in high specific activity (2.6 TBq/mmol). Human protox
      expressed in Escherichia coli and purified by affinity chromatography is used
      with [3H]AzTHP to characterize the herbicide/substrate binding site. Specific
      binding of [3H]AzTHP to human protox is rapid, completely reversible in the
      absence of light with a Kd of 93 nM, and competitively inhibited by the 5
      propargyloxy analogue and by acifluorfen, which are known to bind at the
      substrate (protoporphyrinogen) site. The Bmax establishes one [3H]AzTHP binding
      site per FAD. Diphenyleneiodonium, proposed to inhibit protox by interaction with
      the FAD cofactor, inhibits enzyme activity by 48% at 100 micro M without
      affecting [3H]AzTHP binding in the presence or absence of substrate, suggesting
      that the herbicide binding site may not be proximal to FAD. The first step has
      been taken in photoaffinity labeling the herbicide/substrate site with [3H]AzTHP
      resulting in apparent covalent derivatization of 13% of the herbicide binding
      site.

PMID- 9578578
TI  - Delta subunit of rat liver mitochondrial ATP synthase: molecular description and
      novel insights into the nature of its association with the F1-moiety.
AB  - The F1 moiety of ATP synthase complexes consists of five subunit types in the
      stoichiometric ratio alpha 3, beta 3, gamma, delta epsilon. Of these, the delta
      subunit has received very little attention in the study of F1 preparations from
      eukaryotic cells. Although recently shown to associate tightly with the beta
      subunit [Pedersen, P. L., Hullihen, J., Bianchet, M., Amzel, L. M., and Lebowitz,
      M. S. (1995) J. Biol. Chem. 270, 1775-1784], the delta subunit is not resolved in
      the X-ray structure of either the rat liver or bovine heart enzyme. For these
      reasons, the novel studies reported here were designed both to provide a
      molecular description of the rat liver delta subunit and to gain insight into the
      nature of its interaction with F1. The rat liver delta subunit was cloned from a
      lambda gt11 library, sequenced, overexpressed in Escherichia coli (E. coli) in
      fusion with the maltose binding protein, and, after cleavage of the latter
      protein, purified to homogeneity. The purified delta subunit (MW = 14.7 kDa) was
      shown by circular dichroism spectroscopy to be highly structured and to exhibit
      about 25% sequence identity to the chloroplast and E. coli epsilon subunits,
      frequently regarded as homologues of higher eukaryotic delta subunits.
      Significantly, and in contrast to the chloroplast and E. coli epsilon subunits,
      which are readily removed from their parent F1 moieties after treatment
      respectively with ethanol and lauryldimethylamine oxide, the rat liver delta
      subunit remained tightly bound to F1 under these relatively mild conditions. For
      the above reasons, four types of experiments were carried out on rat liver F1 in
      order to (1) determine the accessibility of the delta subunit to both specific
      antibodies and to proteases, (2) establish the effect of nucleotides on this
      subunit's accessibility, (3) identify in cross-linking studies with
      disuccinimidyl glutarate this subunit's most reactive neighbor, and (4) determine
      whether this subunit can be dissociated from F1 by using ionic detergents while
      leaving the remaining complex intact. The data derived from this detailed set of
      studies (a) supports the view that the rat liver F1-delta subunit is in very
      close proximity to the gamma subunit near the bottom of the F1 molecule but does
      not penetrate deeply into the central core, (b) shows that within F1 the delta
      subunit's N-terminus is exposed while its C-terminus is masked, (c) indicates
      that access to the delta subunit is shielded in part by the alpha, beta, and
      gamma subunits and changes during the catalytic cycle of F1, and (d) implicates
      the delta subunit as important for the structural stability of the F1 unit. These
      novel findings on a higher eukaryotic F1-delta subunit are discussed in
      relationship to earlier studies on the related epsilon subunits from both
      chloroplasts and E. coli.

PMID- 9578580
TI  - Stability effects of increasing the hydrophobicity of solvent-exposed side chains
      in staphylococcal nuclease.
AB  - A total of fifty single site surface phenylalanine substitution mutants have been
      made in the model protein staphylococcal nuclease. The fifty residues that were
      replaced with phenylalanine were chosen to give a broad sampling of solvent
      accessibility, secondary structure, and backbone conformations. The change in the
      stability of each mutant protein relative to wild type was measured by guanidine
      hydrochloride denaturation. These results were compared to previous results
      obtained when these same sites were substituted with an alanine and a glycine. By
      this means, changes in the stability due to the loss of interactions of the wild
      type side chain can be separated from the effects of introducing the bulky,
      hydrophobic phenylalanine in these solvent-exposed positions. In general, our
      results agree with the conventional wisdom that placing a hydrophobic residue in
      a solvent-exposed position is destabilizing in most cases, but less destabilizing
      than most changes in the hydrophobic core of the protein. However, the degree to
      which a hydrophobic surface substitution destabilizes or stabilizes a globular
      protein is highly context-dependent, with some mutations being as destabilizing
      as those in the core. This indicates that steric and packing considerations are
      also important on the surface of a globular protein but generally are not as
      important as in the interior. No evidence for the widespread occurrence of the so
      called reverse hydrophobic effect at solvent-exposed sites was found. In
      addition, this survey of numerous sites suggests that previous measurements of
      alpha-helix "propensities" often seriously underestimate the importance of the
      environment of the side chain.

PMID- 9578579
TI  - Mammalian cytosolic DnaJ homologues affect the hsp70 chaperone-substrate reaction
      cycle, but do not interact directly with nascent or newly synthesized proteins.
AB  - Members of the hsp70 family of molecular chaperones interact with and stabilize
      nascent polypeptides during synthesis and/or translocation into organelles. The
      bacterial hsp70 homologue DnaK requires the DnaJ cofactor for its reaction cycle
      with polypeptide substrates. DnaJ stimulates the ATPase activity of the DnaK
      chaperone and thereby is thought to regulate the affinity of DnaK for its protein
      target. Herein we have analyzed some of the biochemical properties of two
      mammalian cytosolic DnaJ homologues, the hdj-1 and hdj-2 proteins. We were
      particularly interested in examining the proposal that DnaJ homologues are the
      first molecular chaperones to interact directly with nascent polypeptides.
      Nascent/newly synthesized proteins, nascent polypeptides released from the
      ribosome by puromycin, or polypeptides misfolded as a result of incorporation of
      an amino acid analogue were not found in complexes with either of the two HeLa
      cell DnaJ homologues. We still were unable to demonstrate any interactions
      between hdj-1p and nascent/newly synthesized proteins even after chemical cross
      linking. We did find that hdj-1p, like bacterial DnaJ, stimulated the ATPase
      activity of hsp70. Stable complex formation between hsp70 and an unfolded
      polypeptide substrate in vitro was found to be reduced in the presence of hdj-1p
      and ATP. Thus, while hdj-1p likely does function as a cofactor for the hsp70
      chaperone, having effects on hsp70's ATPase activity and conformation/oligomeric
      structure and the stability of hsp70-substrate complexes, it was not observed to
      interact directly with nascent/newly synthesized proteins. Rather, hdj-1p likely
      serves a regulatory role, governing the reaction cycle of hsp70 with polypeptide
      substrates.

PMID- 9578581
TI  - Erythrosin isothiocyanate selectively labels lysine464 within an ATP-protectable
      binding site on the Ca-ATPase in skeletal sarcoplasmic reticulum membranes.
AB  - Conditions that permit the selective modification of an ATP-protectable site on
      the Ca-ATPase in skeletal sarcoplasmic reticulum (SR) membranes using erythrosin
      isothiocyanate (Er-ITC) have been identified. The major labeling site for Er-ITC
      has been identified using reversed-phase HPLC and positive FAB mass spectrometry
      after exhaustive tryptic digestion of the Er-ITC-modified Ca-ATPase. An ATP
      protectable peptide corresponding to M452NVFNTEVRNLSK464VER467 is modified by Er
      ITC, the average mass of which is 2830.1 +/- 0.3 Da. The exclusive modification
      of lysine residues indicates Lys464 as the site of Er-ITC modification.
      Derivatization with Er-ITC diminishes the secondary activation of steady-state
      ATPase activity and the rate of dephosphorylation by millimolar concentrations of
      ATP. In contrast, in the presence of micromolar ATP concentrations Er-ITC
      modification of the Ca-ATPase does not affect (i) the apparent affinity of ATP,
      (ii) the maximal extent of phosphoenzyme formation by ATP, (iii) the rate of
      steady-state ATP hydrolysis, or (iv) the rate of dephosphorylation of the Ca
      ATPase. Furthermore, ATP utilization by the Ca-ATPase is unaffected by detergent
      solubilization, irrespective of Er-ITC modification, indicating that the
      secondary activation of ATP hydrolysis involves a single Ca-ATPase polypeptide
      chain. Therefore, Er-ITC does not interfere with the normal structural
      transitions associated with phosphoenzyme decay. Rather, these results indicate
      that Er-ITC bound to Lys464 interferes with either ATP binding to a low-affinity
      site or the associated structural transitions that modulate the rate of enzyme
      dephosphorylation.

PMID- 9578582
TI  - Discrepancies between the NMR and X-ray structures of uncomplexed barstar:
      analysis suggests that packing densities of protein structures determined by NMR
      are unreliable.
AB  - The crystal structure of the C82A mutant of barstar, the intracellular inhibitor
      of the Bacillus amyloliquefaciens ribonuclease barnase, has been solved to a
      resolution of 2.8 A. The molecule crystallizes in the space group I41 with a
      dimer in the asymmetric unit. An identical barstar dimer is also found in the
      crystal structure of the barnase-barstar complex. This structure of uncomplexed
      barstar is compared to the structure of barstar bound to barnase and also to the
      structure of barstar solved using NMR. The free structure is similar to the bound
      state, and there are no significant main-chain differences in the 27-44 region
      involved in barstar binding to barnase. The C82A structure shows significant
      differences from the average NMR structure, both overall and in the binding
      region. In contrast to the crystal structure, the NMR structure shows an
      unusually high packing value based on the occluded surface algorithm, indicating
      errors in the packing of the structure. We show that the NMR structures of
      homologous proteins generally show large differences in packing value, while the
      crystal structures of such proteins have very similar packing values, suggesting
      that protein packing density is not well determined by NMR.

PMID- 9578583
TI  - Conformational changes in yeast pyruvate kinase studied by 205Tl+ NMR.
AB  - The interaction of the monovalent cation with yeast pyruvate kinase (yPK) has
      been investigated by 205Tl+ NMR. TlNO3 activates yPK to 80-90% activity compared
      to KCl with an apparent Ka of 1.00 +/- 0.03 mM in the presence of 4 mM Mn(NO3)2
      as the activating divalent cation. At higher concentrations of Tl+, enzyme
      inhibition is observed with an apparent KI of 180 +/- 10 mM. The extent of
      inhibition is dependent on the nature and concentration of the divalent cation.
      The effect of Mn2+ on the 1/T1 and 1/T2 values of 205Tl+ in the presence of yPK
      was determined at 173.02 MHz (300 MHz, 1H) and 346.03 MHz (600 MHz, 1H). The
      temperature dependence of the relaxation rates indicates that fast exchange
      conditions prevail for 205Tl+ longitudinal relaxation rates. The correlation
      time, tauc, for the Mn2+-205Tl+ interaction was estimated by a frequency
      dependence of 1/T1m for several enzyme complexes, and an average value of tauc
      was determined to be 0.91 ns. The distance between Tl+ and Mn2+ at the active
      site of yPK was calculated from the paramagnetic contribution of Mn2+ to the
      longitudinal (1/T1m) relaxation rates of Tl+ bound to yPK. For the apo yPK
      complex, the Tl+ to Mn2+ distance is 6.7 +/- 0.2 A. Upon addition of
      phosphoenolpyruvate (PEP) to form the yPK-Tl-Mn-PEP complex, the inter-cation
      distance decreases to 6.1 +/- 0.3 A. The addition of the allosteric activator
      fructose 1,6-bisphosphate (FBP) to form the yPK-Tl+-Mn2+-PEP-FBP complex gives an
      intermetal distance of 6.2 +/- 0.2 A. In the yPK-Tl-Mn-FBP complex, a Tl+-Mn2+
      distance of 6.0 +/- 0.1 A is observed, indicating that FBP causes a
      conformational change at the active site in the absence of PEP. Analogous 205Tl
      NMR experiments with competitive inhibitors of PEP (oxalate, BrPEP) indicate that
      these ligands do not induce the same conformational changes as do the
      physiological substrates and activators. Similar experiments with the
      nonallosteric rabbit muscle PK were also performed and analyzed.

PMID- 9578584
TI  - Melting of a DNA hairpin without hyperchromism.
AB  - UV absorbance spectroscopy is the most common method for detecting nucleic acid
      structural transitions and obtaining thermodynamic parameters. UV-detected
      melting has been used to determine stabilities of nucleic acid hairpins,
      duplexes, triplexes, and higher order structures and to determine thermodynamic
      effects of unusual or modified bases and mismatched base-pairs. We report that in
      some cases UV absorbance spectroscopy is an inadequate analytical technique for
      these purposes. Some critical transitions are invisible to UV absorbance
      spectroscopy. For example, the conversion of dodecamer d(CGCAAATTCGCG) from
      hairpin to random coil is not accompanied by hyperchromism. Circular dichroism
      (CD) spectroscopy (263 nm) clearly detects two transitions for this dodecamer,
      each giving a pronounced change in ellipiticity. The concentration dependence of
      the low-temperature transition and the concentration independence of the high
      temperature transition indicate that the predominant state converts from duplex
      to hairpin to random coil as the temperature increases. These assignments are
      confirmed by comparison to oligonucleotides of similar sequence that undergo a
      hairpin to coil transition only. In contrast to CD spectroscopy, UV absorbance
      spectroscopy shows only a single transition. The transition detected by UV
      absorbance spectroscopy corresponds to the low-temperature transition detected by
      CD. UV absorbance spectroscopy does not detect the second transition at any
      wavelength (from 218 to 310 nm) (by changes) in either absorbance or its
      derivative with temperature.

PMID- 9578585
TI  - Influence of proximal side mutations on the molecular and electronic structure of
      cyanomet myoglobin: an 1H NMR study.
AB  - A series of proximal side mutants of sperm whale metmyoglobin (metMb) that
      involves residues which provide hydrogen bonds to the axial His and heme have
      been prepared, and the CO binding and solution molecular and electronic structure
      has been investigated by 1H NMR. These include Ser92(F7), whose O gamma serves as
      a hydrogen-bond acceptor to the axial His ring NdeltaH and whose O gamma H serves
      as hydrogen-bond donor to the 7-propionate carboxylate, and His97(FG3) whose ring
      provides the other hydrogen-bond donor to the 7-propionate carboxylate. 2D NMR
      data on the S92A-metMbCN, S92P-metMbCN and H97F-metMbCN show that the distal
      structure is completely conserved and that proximal side structural changes are
      highly localized. For the S92A-metMbCN, altered dipolar contacts to the F-helix
      backbone show that the axial His imidazole has rotated clockwise by approximately
      10 degrees relative to a stationary heme, while in H97F-metMbCN, the altered heme
      E helix backbone contacts reveal that the heme has rotated counterclockwise by
      approximately 3 degrees relative to a conserved axial His. The pattern of axial
      His rotation was qualitatively predicted by energy minimization calculations. The
      assignments and conserved structural elements allow the determination of a set of
      magnetic axes whose major magnetic axis is unchanged with respect to WT and
      confirms that local distal, and not proximal, interactions control the
      orientation of the major magnetic axis and, by inference, the degree and
      direction of tilt of the Fe-CN from the heme normal. The rhombic magnetic axes in
      S92A-metMbCN are rotated approximately 10 degrees in the opposite direction from
      the established approximately 10 degrees rotation for the axial His ring as
      expected. It is shown, moreover, that the pairwise alpha-, gamma-meso vs beta-,
      delta-meso-H hyperfine shift differences are well predicted by the change in the
      location of the rhombic magnetic axes. Carbon monoxide ligation rates experience
      minor but systematic perturbation for the S92A substitutions which confirms an
      influence (albeit very small) for axial His orientation on ligand affinity.

PMID- 9578586
TI  - What affects the effect of 2'-alkoxy modifications? 1. Stabilization effect of 2'
      methoxy substitutions in uniformly modified DNA oligonucleotides.
AB  - The thermostability of hybrid duplexes with uniformly 2'-methoxy modified DNA
      strands (D'R and RD'), their unmodified DNA:RNA counterparts (DR and RD), and
      corresponded RNA:RNA (RR) duplexes for six sequences with different GC and
      deoxypyrimidine (dPy) content was measured. The linear correlation between the
      total stabilization effect of 2'-methoxy modifications (Delta DeltaG(o)37(D'R
      DR)) and the relative stability of corresponding unmodified hybrids compared to
      the RR counterparts (Delta DeltaG(o)37(RR-DR)) suggests that the initial
      conformational and the thermodynamic state of the "parent" unmodified hybrid
      governs the effect of 2'-methoxy (and may be other 2'-alkoxy) modifications whose
      mechanism of action includes an S --> N conformational shift resulting in an RNA
      like A-form duplex. We also found a correlation between the "hydrophobic" part of
      the total effect (Delta DeltaG(o)37(D'R-RR)) and the dA fraction in the modified
      DNA strand, suggesting that the "hydrophobic" effect of the 2'-methoxy groups
      results mainly from intraresidue steric effects increasing rigidity of the
      modified sugar rings. The correlations observed enabled us to predict the
      stability of hybrids with 2'-methoxy modified DNA strands for any sequence except
      for sequences with (dU)10 and (dA)10 strings.

PMID- 9578587
TI  - Effects of pH on rhodopsin photointermediates from lumirhodopsin to metarhodopsin
      II.
AB  - Time-resolved absorption difference spectra of membrane suspensions of bovine
      rhodopsin at pH 5, 6, 7, 8, 9, and 10 were collected in the time range from 1
      micro s to 200 ms after laser photolysis with 7-ns pulses of 477-nm light. The
      data were analyzed using singular value decomposition (SVD) and global
      exponential fitting. At pH 7 the data agree well with previously obtained data
      (Thorgeirsson et al. (1993) Biochemistry 32, 13861-13872) with fits improved at
      all pH's by inclusion of a small component due to an absorbance change caused by
      rotational diffusion which is detectable even at magic angle polarization. A
      "square scheme" suggested to best explain the previous data, which involves two
      branches following decay of the lumi intermediate with pathways (1) lumi -->
      MI480 right harpoon over left harpoon MII and (2) lumi right harpoon over left
      harpoon MI380 --> MII, could be confirmed throughout the entire pH range.
      However, to account for the increased rate of the MII --> MI480 reaction in path
      1 for rising pH values, we propose that the MII in the square scheme consists of
      deprotonated MII and protonated MIIH+ forms in rapid equilibrium with each other,
      resulting in an extended square scheme and increasing the number of 380-nm
      products from two to three. In addition to the kinetic processes described by the
      extended square scheme, above pH 8 fast ( approximately 10 micro s) and slow (
      approximately 50 ms) components were found. The fast component was assigned to
      the decay of a blue-shifted lumi intermediate, and the slow component, resolvable
      only at pH 10, was assigned to formation of a 450 nm absorbing photoproduct.

PMID- 9578588
TI  - Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of
      phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine
      phosphorylation.
AB  - Salts of the trace element vanadium, such as sodium orthovanadate and vanadyl
      sulfate (VS), exhibit a myriad of insulin-like effects, including stimulation of
      glycogen synthesis and improvement of glucose homeostasis in type I and type II
      animal models of diabetes mellitus. However, the cellular mechanism by which
      these effects are mediated remains poorly characterized. We have shown earlier
      that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6
      kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin
      receptor (CHO-HIR cells) [Pandey, S. K., Chiasson, J.-L., and Srivastava, A. K.
      (1995) Mol. Cell. Biochem. 153, 69-78]. In the present studies, we have
      investigated if similar to insulin, VS also activates phosphatidylinositol 3
      kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP
      kinase, and p70s6k pathways contributes to glycogen synthesis. Treatment of CHO
      HIR cells with VS resulted in increased glycogen synthesis and PI3-k activity
      which were blocked by pretreatment of the cells with wortmannin and LY294002, two
      specific inhibitors of PI3-k. On the other hand, PD98059 and rapamycin, specific
      inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to
      inhibit VS-stimulated glycogen synthesis. Moreover, VS-stimulated glycogen
      synthesis and PI3-k were observed without any change in the tyrosine
      phosphorylation of insulin receptor (IR) beta-subunit but were associated with
      increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). In
      addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS
      stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to
      interact and thereby activate PI3-k in response to VS. Taken together, these
      results provide evidence that tyrosine phosphorylation of IRS-1 and activation of
      PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen
      synthesis independent of IR-tyrosine phosphorylation.

PMID- 9578589
TI  - Identification of the minimum essential region in the II-III loop of the
      dihydropyridine receptor alpha 1 subunit required for activation of skeletal
      muscle-type excitation-contraction coupling.
AB  - We have previously shown that among several peptides encompassing various regions
      of the II-III loop of the dihydropyridine receptor alpha 1 subunit, only one
      peptide corresponding to the Thr671-Leu690 region (designated as peptide A)
      activated ryanodine binding to and induced calcium release from the sarcoplasmic
      reticulum [El-Hayek et al. (1995) J. Biol. Chem. 270, 22116-22118]. To further
      localize within peptide A the minimum unit essential for activating the
      sarcoplasmic reticulum calcium release channel, we synthesized variously
      truncated forms of peptide A and examined their ability to activate ryanodine
      binding. We found that the carboxy-terminal 10-residue region of peptide A
      encompassing Arg681-Leu690 (peptide As-10; s, skeletal muscle-type sequence)
      activated ryanodine binding in a RyR1-specific manner and induced calcium release
      even more efficiently than the 20-residue peptide A. Further truncation of one or
      more residue(s) of peptide As-10 virtually abolished both functions of activating
      ryanodine binding and inducing Ca2+ release. The activating ability of As-10
      seems to be determined by at least two factors: (1) the distribution of the
      positively charged residues, and (2) the skeletal muscle-type amino acid
      sequence, as deduced from the comparison of various peptides with modified
      structures. These results provide evidence that the minimum essential unit for
      the in situ trigger of skeletal muscle excitation-contraction coupling is
      localized in the Arg681-Leu690 region of the II-III loop of the alpha 1 subunit
      of the dihydropyridine receptor.

PMID- 9578590
TI  - hnRNP A2 selectively binds the cytoplasmic transport sequence of myelin basic
      protein mRNA.
AB  - Segregation of mRNAs in the cytoplasm of polar cells has been demonstrated for
      proteins involved in Xenopus and Drosophila oogenesis, and for some proteins in
      somatic cells. It is assumed that vectorial transport of the messages is
      generally responsible for this localization. The mRNA encoding the basic protein
      of central nervous system myelin is selectively transported to the distal ends of
      the processes of oligodendrocytes, where it is anchored to the myelin membrane
      and translated. This transport is dependent on a 21-nucleotide cis-acting segment
      of the 3'-untranslated region (RTS). Proteins that bind to this cis-acting
      segment have now been isolated from extracts of rat brain. A group of six 35-42
      kDa proteins bind to a 35-base oligoribonucleotide incorporating the RTS, but not
      to several oligoribonucleotides with the same composition but randomized
      sequences, thus establishing specificity for the base sequence in the RTS. The
      most abundant of these proteins has been identified, by Edman sequencing of
      tryptic peptides and mass spectroscopy, as heterogeneous nuclear
      ribonucleoprotein (hnRNP) A2, a 36-kDa member of a family of proteins that are
      primarily, but not solely, intranuclear. This protein was most abundant in
      samples from rat brain and testis, with lower amounts in other tissues. It was
      separated from the other polypeptides by using reverse-phase HPLC and shown to
      retain preferential association with the RTS. In cultured oligodendrocytes, hnRNP
      A2 was demonstrated by confocal microscopy to be distributed throughout the
      nucleus, cell soma, and processes.

PMID- 9578591
TI  - Mutagenesis by peroxy radical is dominated by transversions at deoxyguanosine:
      evidence for the lack of involvement of 8-oxo-dG1 and/or abasic site formation.
AB  - Oxidative damage of DNA by endogenously generated oxygen radicals contributes to
      the mutagenic process. Hydroxy, alkoxy, and peroxy radicals all have the
      potential to react with DNA, giving rise to strand breaks and potentially
      mutagenic oxidative base damage. Although reactions of the hydroxy radical with
      DNA have been well studied, far less is known about the reactivities of these
      other radicals with DNA and their mutation-inducing potential. Frequencies of DNA
      base modifications and strand break densities caused by peroxy radical (ROO*)
      oxidation were measured by glyoxal gel electrophoretic analysis. We report the
      spectrum of mutations induced in Escherichia coli upon transfection with peroxy
      radical treated DNA carrying the lacZ alpha gene as a reporter. Transfection of
      DNA exposed to micromolar amounts of peroxy radical resulted in a 30-fold
      increase in mutation frequency in non-SOS-inducible cells. Sequencing analysis of
      DNA isolated from mutants showed that among base substitution mutants 88%
      consisted of transversions at G, with a nearly equal number of G --> C and G -->
      T mutants. Transition mutations were rarely detected, in contrast to control
      experiments. Electrophoretic analysis of peroxy radical treated DNA exposed to
      NaOH, Nth, and Fpg proteins demonstrated that abasic sites are not formed to any
      detectable degree. The oxidative G lesions are sensitive to digestion by the Fpg
      protein. We were unable to detect the formation of 8-oxo-dG by
      HPLC/electrochemical analysis of peroxy radical oxidation of dG, suggesting that
      the G --> T transversions were not caused by this base lesion.

PMID- 9578592
TI  - Evaluation of cytochrome P450 mechanism and kinetics using kinetic deuterium
      isotope effects.
AB  - In this paper two hypotheses are tested: (i) the active oxygen species is similar
      in energetics for all cytochrome P450 (CYP) enzymes and (ii) linear free-energy
      relationships can be used to evaluate the mechanism of the reaction of these
      enzymes. A series of intramolecular isotope effects were determined and compared
      for CYPs 1A2, 2B1, 2C9, 2E1, and P450cam. The results indicate that the isotope
      effects are very similar for each of these isoforms of P450 and that the first
      hypothesis is likely to be true. Attempts to establish a linear free-energy
      relationship were only moderately successful: log Vmax = 0.11sigma+p + 1.73; r2 =
      0.588. It was determined, through the use of intermolecular isotope effects, that
      the rates of hydrogen atom abstraction are masked. Thus, the second hypothesis is
      found to be false. This is likely to be a general result for CYP reactions, and
      linear free-energy relationships can only be used to determine the mechanism
      under very special circumstances. In all cases, the rate-limiting step should be
      evaluated with isotope effect experiments before any mechanistic conclusions can
      be drawn. If the intermolecular isotope effects are found to be masked, no
      mechanistic conclusion can be drawn from the linear free-energy relationship
      study.

PMID- 9578593
TI  - Disruption of the heme iron-proximal histidine bond requires unfolding of
      deoxymyoglobin.
AB  - The unfolding behavior of 10 different distal heme pocket mutants of sperm whale
      deoxymyoglobin (deoxyMb) has been investigated. The effects of distal histidine
      (His 64) replacement were the primary focus; however, mutations at Leu 29, Val
      68, and Ile 107 were also examined. Formation of the spectroscopically
      distinguishable heme intermediate (I') of deoxyMb was tracked as a function of pH
      and guanidinium chloride (GdmCl) concentration. The appearance of this
      intermediate signals cleavage of the iron-proximal histidine (His 93) bond. The
      key observations are as follows. (1) None of the distal heme pocket mutations
      investigated alter the nature of the heme intermediates that are formed under low
      pH unfolding conditions. (2) Unfolding of deoxyMb at high concentrations of GdmCl
      proceeds through the same heme intermediates that occur under low pH conditions.
      (3) The rate of the iron-histidine bond cleavage in an acidic medium is
      dramatically slowed when large hydrophobic residues (Leu and Phe) replace the
      distal histidine, whereas there is little correlation between the polarity of the
      residue at position 64 and the rate of denaturation by GdmCl. (4) However, apolar
      residues at position 64 enhance significantly the equilibrium resistance of
      deoxyMb to iron-histidine bond cleavage under both low pH and high GdmCl
      unfolding conditions. There is a direct correlation between the equilibrium pH
      and GdmCl values for maximum intermediate formation and the stabilities of the
      corresponding apoproteins. Collectively, these observations suggest that
      substantial unfolding of deoxyMb is required for Fe(II)-His 93 bond cleavage.
      Unlike the situation for aquometMb, heme loss from deoxyMb is not driven by
      protonation of the proximal histidine ligand. Instead, the process is mediated by
      more global unfolding of the protein that leads to solvation of the prosthetic
      group.

PMID- 9578594
TI  - Posttranslational elevation of cytochrome P450 3A levels and activity by dimethyl
      sulfoxide.
AB  - The molecular mechanisms by which dimethyl sulfoxide (DMSO) enhances CYP3A
      protein in phenobarbital-treated primary cultured rat hepatocytes were examined.
      DMSO treatment rapidly increased CYP3A protein levels in the absence of an
      increase in CYP3A mRNA levels or an increase in CYP2B protein or mRNA levels.
      CYP3A levels were increased approximately 3.7- and 9-fold following 0.1% DMSO
      treatment for 6 and 48 h, respectively. Analyses of the polysomal distribution of
      CYP3A mRNA suggested that DMSO treatment did not significantly alter the
      translational efficiency of the CYP3A mRNA. Comparative analyses of
      immunodetectable protein levels following treatment with cycloheximide showed
      that DMSO clearly decreased the rate of CYP3A protein turnover but not that of
      CYP2B. Examination of testosterone metabolism in hepatocyte cultures revealed
      that DMSO pretreatment increased CYP3A-catalyzed 2 beta- and 6 beta-testosterone
      hydroxylation. When DMSO was in the culture medium, no inhibitory affect on CYP3A
      catalyzed testosterone metabolism was observed, although a slight (15-21%)
      inhibitory effect was noted for CYP2B-catalyzed 16 alpha- and 16 beta
      testosterone hydroxylation. These data provide evidence that DMSO increased CYP3A
      protein levels as a result of decreased protein degradation. DMSO increased both
      immunodetectable CYP3A protein levels and catalytic activity, in contrast to
      compounds that have been reported to stabilize CYP3A protein and inhibit
      activity.

PMID- 9578595
TI  - Matrix protein mRNA levels in canine meniscus cells in vitro.
AB  - The resident cells of the meniscus synthesize a fibrocartilaginous extracellular
      matrix in vivo composed predominantly of type I collagen fibers. To increase our
      understanding of matrix biosynthesis by meniscus cells in vitro, we examined
      matrix protein mRNA levels in cultured meniscus cells isolated from skeletally
      mature dogs. The mRNA levels of five matrix protein genes (COL1A1, COL2A1,
      aggrecan, COL6A1, and fibronectin) were measured in meniscus cells by Northern
      blotting and compared with those of patellar tendon fibroblasts and femoral
      articular cartilage chondrocytes. In freshly isolated cells (Day 0 cells),
      COL1A1, COL2A1, and aggrecan mRNA levels were low or undetectable in both
      meniscus cells and tendon fibroblasts. In intact meniscus tissue, COL1A1 mRNA
      levels were also low or undetectable. COL2A1 and aggrecan mRNA transcripts were
      readily observed, however, in Day 0 articular chondrocytes. The levels of
      expression of COL6A1 and fibronectin mRNA transcripts in Day 0 meniscus cells
      were intermediate between higher articular chondrocyte levels and lower tendon
      fibroblast levels. After 1 week in monolayer culture (Day 7 cells), meniscus
      cells expressed readily detectable levels of COL1A1 mRNA transcripts, similar to
      that observed for cultured tendon fibroblasts. COL1A1 mRNA transcripts were
      either not detected or detected at very low levels in monolayer cultures of
      articular chondrocytes. COL2A1 and aggrecan mRNA transcripts were readily
      detected in cultured articular chondrocytes but not in meniscus cells or in
      tendon fibroblasts. All three types of cells continued to express COL6A1 and
      fibronectin mRNA transcripts after 1 week in culture. These results demonstrate
      that the patterns of expression of COL1A1 and COL2A1 mRNA transcripts by meniscus
      cells are similar to those of tendon fibroblasts and dissimilar to those of
      articular chondrocytes both in freshly isolated cells and in monolayer cultured
      cells. This mRNA expression pattern supports the idea that monolayer culture of
      meniscus cells results in the expression of a predominantly fibroblastic
      phenotype.

PMID- 9578596
TI  - Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in
      microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations.
AB  - Individuals with drug metabolism polymorphisms involving CYP2C enzymes exhibit
      deficient oxidation of important therapeutic agents, including S-mephenytoin,
      omeprazole, warfarin, tolbutamide, and nonsteroidal anti-inflammatory drugs.
      While recombinant CYP2C19 and CYP2C9 proteins expressed in yeast or Escherichia
      coli have been shown to oxidize these agents, the capacity of the corresponding
      native P450s isolated from human liver to do so is ill defined. To that end, we
      purified CYP2C19, CYP2C9, and CYP2C8 from human liver samples using conventional
      chromatographic techniques and examined their capacity to oxidize S-mephenytoin,
      omeprazole, and tolbutamide. Upon reconstitution, CYP2C19 metabolized S
      mephenytoin and omeprazole at rates that were 11- and 8-fold higher,
      respectively, than those of intact liver microsomes, whereas neither CYP2C9 nor
      CYP2C8 displayed appreciable metabolic activity with these substrates. CYP2C19
      also proved an efficient catalyst of tolbutamide metabolism, exhibiting a
      turnover rate similar to CYP2C9 preparations (2.0-6.4 vs 2.4-4.3 nmol
      hydroxytolbutamide formed/min/nmol P450). The kinetic parameters of CYP2C19
      mediated tolbutamide hydroxylation (Km = 650 microM, Vmax = 3.71 min-1) somewhat
      resembled those of the CYP2C9-catalyzed reaction (Km = 178-407 microM, Vmax =
      2.95-7.08 min-1). Polyclonal CYP2C19 antibodies markedly decreased S-mephenytoin
      4'-hydroxylation (98% inhibition) and omeprazole 5-hydroxylation (85% inhibition)
      by human liver microsomes. CYP2C19 antibodies also potently inhibited (>90%)
      microsomal tolbutamide hydroxylation, which was similar to the inhibition (>85%)
      observed with antibodies to CYP2C9. Moreover, excellent correlations were found
      between immunoreactive CYP2C19 content, S-mephenytoin 4'-hydroxylase activity (r
      = 0.912; P < 0. 001), and omeprazole 5-hydroxylase activity (r = 0.906; P <
      0.001) in liver samples from 13-17 different subjects. A significant relationship
      was likewise observed between microsomal tolbutamide hydroxylation and CYP2C9
      content (r = 0.664; P < 0.02) but not with CYP2C19 content (r = 0.393; P =
      0.184). Finally, immunoquantitation revealed that in these human liver samples,
      expression of CYP2C9 (88. 5 +/- 36 nmol/mg) was 5-fold higher than that of
      CYP2C19 (17.8 +/- 14 nmol/mg) and nearly 8-fold higher than that of CYP2C8 (11.5
      +/- 12 nmol/mg). Our results, like those obtained with recombinant CYP2C enzymes,
      indicate that CYP2C19 is a primary determinant of S-mephenytoin 4'-hydroxylation
      and low-Km omeprazole 5-hydroxylation in human liver. Despite its tolbutamide
      hydroxylase activity, the low levels of hepatic CYP2C19 expression (relative to
      CYP2C9) may preclude an important role for this enzyme in hepatic tolbutamide
      metabolism and any polymorphisms thereof.

PMID- 9578598
TI  - Cellobiose dehydrogenase from Schizophyllum commune: purification and study of
      some catalytic, inactivation, and cellulose-binding properties.
AB  - Cellobiose dehydrogenase (CDH) of Schizophyllum commune was purified to
      homogeneity. It is a glycoprotein with a molecular mass of 102, 000. Cellulosic
      substrates can serve as substrates for CDH. Cytochrome c, dichlorophenol
      indophenol, ferricyanide, and oxygen can be reduced by the enzyme. CDH is stable
      in the pH range of 4-11 and up to 35 degrees C. The enzyme keeps active at high
      concentrations of H2O2. In the presence of cellobiose and Fe3+, incubation of CDH
      resulted in its inactivation and the degree of the inactivation was dependent
      mainly on the amount of CDH and cellobiose present. CDH has a distinct and
      specific affinity to cellulose and showed the strongest binding to acid-treated
      cellulose. The adsorption isotherm data fitted the Langmuir-type equation. The uv
      visible spectra of the oxidized and reduced states of CDH showed a typical
      cytochrome b-type pattern. Addition of dithionite eliminated the adsorption
      between 440 and 500 nm, which indicates the presence of a flavin group in CDH.

PMID- 9578597
TI  - Load-controlled compression of articular cartilage induces a transient
      stimulation of aggrecan gene expression.
AB  - The effects of short- and long-term load-controlled compression on the levels of
      aggrecan mRNA have been determined. Results show that a compressive stress of 0.1
      MPa on bovine articular cartilage explants for 1, 4, 12, and 24 h produces a
      transient up-regulation of aggrecan mRNA synthesis. At 1 h, aggrecan mRNA levels
      in loaded explants were increased 3.2-fold compared to control explants. At
      longer times (>/=4 h), the levels of aggrecan mRNA returned to baseline values or
      stayed slightly higher. There is a dose dependence in the response of the explant
      to increasing levels of compressive stress (0-0.5 MPa) for 1 h. Aggrecan mRNA
      levels increased 2- to 3-fold at 0-0.25 MPa. At 0.5 MPa, the level of aggrecan
      mRNA was lower than those at 0.1 and 0.25 MPa. This dose-dependent effect
      suggests a reversal of the stimulatory effects of compression on aggrecan gene
      expression at higher loads. After 24 h of compression, the levels of aggrecan
      mRNA in explants subjected to any of the stress levels were not significantly
      different from those in control explants. The stimulatory effect of 0.1 MPa
      compressive stress on aggrecan mRNA levels was blocked by Rp-cAMP and U-73122,
      indicating the involvement of the classical signal transduction pathways in the
      mechanical modulation of aggrecan gene expression. The responses of link protein
      mRNA to compression paralleled those of aggrecan, while there was no significant
      change in expression of the gene for the housekeeping protein elongation factor-1
      alpha. The results indicate that articular cartilage chondrocytes can respond to
      short-term compressive loads by transiently up-regulating expression of the
      aggrecan gene. The fact that long-term compression did not significantly alter
      aggrecan mRNA levels suggests that previously observed inhibitory effects of
      prolonged static compression on proteoglycan synthesis in articular cartilage may
      be, for the most part, mediated through mechanisms other than suppression of
      aggrecan mRNA levels.

PMID- 9578599
TI  - The Ah receptor can bind ligand in the absence of receptor-associated heat-shock
      protein 90.
AB  - The Ah receptor (AhR) is a soluble ligand-dependent DNA regulatory protein that
      mediates many of the biological responses to 2,3,7, 8-tetrachlorodibenzo-p-dioxin
      (TCDD, dioxin) and related chemicals. In the absence of ligand, the cytosolic
      form of the AhR is found complexed with at least two molecules of hsp90, a heat
      shock protein of 90 kDa. In addition to its role in AhR protein folding and
      ability to repress the inherent nuclear localization, dimerization, and DNA
      binding activity of the AhR, it has been reported that hsp90 is absolutely
      required for maintaining the AhR in its high-affinity ligand binding
      conformation. The ability of high salt conditions (0. 4 M KCl) to dissociate the
      multimeric AhR complex into its monomeric form provides us with an avenue to
      examine the role of hsp90 in AhR ligand binding activity. In contrast to previous
      reports, we demonstrate that salt-dissociated "hsp90-free" AhR from several
      species still retains the ability to specifically bind ligand ([3H]TCDD).
      Although partial inactivation of ligand binding of salt-dissociated rat hepatic
      AhR was observed (to a maximum of 50% of total AhR binding), the presence of
      bound ligand protected against this inactivation. Little or no inactivation of
      the ligand binding ability of salt-dissociated guinea pig or rabbit AhR occurred.
      Our results not only indicate a significant species-difference in AhR ligand
      binding stability and/or activity, but also demonstrate that AhR ligand binding
      activity does not absolutely require the presence of receptor-bound hsp90.

PMID- 9578600
TI  - Comparative study on recombinant chloroplastic and cytosolic ascorbate peroxidase
      isozymes of spinach.
AB  - The spinach stromal, thylakoid-bound, and cytosolic ascorbate peroxidase isozymes
      (EC 1.11.1.11) were overexpressed in Escherichia coli, and their enzymatic
      properties were compared with the respective native isozymes. The purification of
      the recombinant stromal and cytosolic ascorbate peroxidases using the
      conventional column chromatography yielded 0.73 and 2.2 mg of protein/liter of
      bacteria culture with enzyme activities of 800 and 486 micromol min-1 mg protein
      1, respectively. In every respect, the recombinant stromal, thylakoid-bound, and
      cytosolic ascorbate peroxidase isozymes exhibited identical enzymatic properties
      with each native isozyme. Specifically, the recombinant stromal and thylakoid
      bound ascorbate peroxidase isozymes showed high utilization of ascorbate as an
      electron donor and had a very short lifetime in ascorbate-depleted medium.
      Polyclonal antibodies raised against both purified recombinant stromal and
      cytosolic ascorbate peroxidase isozymes were prepared. Both antibodies showed a
      cross-reaction with the recombinant and native ascorbate peroxidase isozymes.

PMID- 9578601
TI  - Purification and characterization of maize starch synthase I and its truncated
      forms.
AB  - Comparison of the protein sequences deduced from the cDNAs of maize granule-bound
      starch synthase, Escherichia coli glycogen synthase, and maize starch synthase I
      (SSI) reveals that maize SSI contains an N-terminal extension of 93 amino acids.
      In order to study the properties of maize SSI and to understand the functions of
      the maize SSI N-terminal extension, the gene coding for full-length SSI (SSI-1)
      and genes coding for N-terminally truncated SSI (SSI-2 and SSI-3) were
      individually expressed in E. coli. Here we describe for the first time the
      purification of a higher plant starch synthase to apparent homogeneity. Its
      kinetic properties were therefore studied in the absence of interfering
      amylolytic enzymes. The specific activities of the purified SSI-1, SSI-2, and SSI
      3 were 22.5, 33.4, and 26.3 micromol Glc/min/mg of protein, respectively, which
      are eight times higher than those of partially purified SSI from developing maize
      endosperm. The full-length recombinant enzyme SSI-1 exhibited properties similar
      to those of the enzyme from maize endosperm. As observed for native maize enzyme,
      recombinant SSI-1 exhibited "unprimed" activity without added primer in the
      presence of 0.5 M citrate. Our results have clearly indicated that the catalytic
      center of SSI is not located in its N-terminal extension. However, N-terminal
      truncation decreased the enzyme affinity for amylopectin, with the Km for
      amylopectin of the truncated SSI-3 being about 60-90% higher than that of the
      full-length SSI-1. These results suggest that the N-terminal extension in SSI may
      not be directly involved in enzyme catalysis, but may instead regulate the enzyme
      binding of alpha-glucans. Additionally, the N-terminal extension may play a role
      in determining the localization of SSI to specific portions of the starch granule
      or it may regulate its interactions with other enzymes involved in starch
      synthesis.

PMID- 9578602
TI  - Dithiocarbamate toxicity toward thymocytes involves their copper-catalyzed
      conversion to thiuram disulfides, which oxidize glutathione in a redox cycle
      without the release of reactive oxygen species.
AB  - We have reported previously that diethyldithio-carbamate (DDC) and pyrrolidine
      dithiocarbamate (PDTC) induce apoptosis in rat thymocytes. Apoptosis was shown to
      be dependent upon the transport of external Cu ions into the cells and was
      accompanied by the oxidation of intracellular glutathione, indicating the
      inducement of pro-oxidative conditions (C. S. I. Nobel, M. Kimland, B. Lind, S.
      Orrenius, and A. F. G. Slater, J. Biol. Chem. 270, 26202-26208, 1995). In the
      present investigation we have examined the chemical reactions underlying these
      effects. Evidence is presented to suggest that dithiocarbamates undergo oxidation
      by CuII ions, resulting in formation of the corresponding thiuram disulfides,
      which are then reduced by glutathione, thereby generating the parent
      dithiocarbamate and oxidized glutathione (glutathione disulfide). Although DDC
      and PDTC were found to partially stabilize CuI ions, limited redox cycling of the
      metal ion was evident. Redox cycling did not, however, result in the release of
      reactive oxygen species, which are believed to be scavenged in situ by the
      dithiocarbamate. DDC and PDTC were, in fact, shown to prevent copper-dependent
      hydroxyl radical formation and DNA fragmentation in model reaction systems. The
      thiuram disulfide disulfiram (DSF) was found to induce glutathione oxidation, DNA
      fragmentation, and cell killing more potently than its parent dithiocarbamate,
      DDC. Of particular importance was the finding that, compared with DDC, the
      actions of DSF were less prone to inhibition by the removal of external copper
      ions with a chelating agent. This observation is consistent with our proposed
      mechanism of dithiocarbamate toxicity, which involves their copper-catalyzed
      conversion to cytotoxic thiuram disulfides.

PMID- 9578603
TI  - Role of Mg2+ in nucleoside diphosphate kinase autophosphorylation.
AB  - Nucleoside diphosphate (NDP) kinase is a ubiquitous enzyme that has been
      described to have regulatory functions. In addition to its classical enzymatic
      activity, NDP kinases have been characterized as inhibitors of metastasis, as a
      factor stimulating gene transcription, and as a protein kinase. In this report we
      show some characteristics of the autophosphorylation of homogeneous NDP kinase
      and make a comparison with that of other proteins in crude extracts. By using
      labeled substrates and fluorescence quenching analysis, we prove that Mg2+ is
      indeed necessary for the two steps of the ping-pong reaction to take place and
      present evidence that NTPs or NDPs, when uncomplexed to divalent cations, may not
      bind the active site in a comparable way to NTP . Mg2+ and NDP . Mg2+. However,
      even extremely small concentrations of Mg2+ suffice for maximal
      autophosphorylation which is obtained with Mg2+ in the nanomolar range and 100
      microM ATP using homogeneous enzyme. Moreover, lower autophosphorylation levels
      were observed with increasing concentrations of Mg2+. The autophosphorylation
      equilibrium varied from 0.19 to 1.6 upon the inclusion of 10 mM EDTA to produce
      low Mg2+ concentrations. Under optimal conditions (low Mg2+ concentrations and
      short incubation times) NDP kinase was the only protein phosphorylated in crude
      extracts from Candida albicans, indicating that the autophosphorylation
      properties of the enzyme are very singular.

PMID- 9578604
TI  - Granulocyte colony-stimulating factor promotes functional maturation of O-2
      generating system during differentiation of HL-60 cells to neutrophil-like cells.
AB  - The effects of granulocyte colony-stimulating factor (G-CSF) on development of O
      2 generating system during differentiation of HL-60 cells to neutrophil-like
      cells have been studied. G-CSF enhanced O-2 generating ability of HL-60 cells
      whose differentiation had been initiated by dimethylsulfoxide (DMSO) or retinoic
      acid (RA). The O-2 generations by the differentiated HL-60 cells in response to
      opsonized zymosan (OZ), formyl-Met-Leu-Phe (fMLP), and IgG-coated zymosan were
      increased two- to fourfold as a result of incubation of the cells undergoing the
      differentiation with G-CSF. The potentiation by G-CSF occurred in a dose
      dependent manner with the maximum effect at about 10 ng/ml G-CSF. The effect of G
      CSF could not be fully explained by up-regulation of the receptor expression on
      the HL-60 cells, because the number of C3bi receptors was not altered by G-CSF,
      whereas the expression of fMLP receptor was enhanced by G-CSF. On the other hand,
      the O2 generation of the differentiated cells activated by phorbol 12-myristate
      13-acetate was not affected by the G-CSF treatment, suggesting that the
      biochemical events in the cells after PKC activation might not be enhanced by G
      CSF. Assuming that the signaling pathways linking OZ or fMLP receptor might be
      enhanced by G-CSF, alteration in the cellular sn-1, 2-diacylglycerols (DAG) level
      upon stimulation with OZ or fMLP was compared between the G-CSF-treated and
      nontreated cells. Whereas DAG level was not increased by the stimulation in the
      cells treated with DMSO alone, a significant increase in DAG level upon the
      stimulation was observed in the cells treated with G-CSF and DMSO. These results
      suggest that G-CSF would enhance the organization of a receptor-linked DAG
      generating system in the differentiating cells, leading the cells to generate
      more O2.

PMID- 9578605
TI  - The covalent coupling of Arg-Gly-Asp-containing peptides to liposomes:
      purification and biochemical function of the lipopeptide.
AB  - With the advent of liposomes as drug carriers, there arises a need for efficient
      targeted delivery in vivo. Proteins coupled to liposomes usually yield
      heterogeneous products that are ill-defined both chemically and in terms of
      spatial orientation. We now report on the disulfide linkage to the surface of
      intact liposomes of a peptide representing one-half of a ligand-receptor pair. An
      RGD-motif-containing peptide was coupled to the phospholipid PDP-DOPE of the
      liposomes by a thiol-disulfide exchange. The resulting lipopeptides were amenable
      to definition by TLC, HPLC, and MS and found to be in a functional orientation
      allowing biochemical interaction with their receptor, the integrin glycoprotein
      IIb-IIIa.

PMID- 9578606
TI  - Expression of catalytically active human cytochrome p450scc in Escherichia coli
      and mutagenesis of isoleucine-462.
AB  - Cytochrome P450scc (P450scc) catalyzes the first step in steroid hormone
      synthesis, the conversion of cholesterol to pregnenolone. Human P450scc has been
      poorly studied due to the difficulty of purifying reasonable quantities of enzyme
      from human tissue. To provide a more convenient source of the human enzyme and to
      enable structure-function studies to be done using site-directed mutagenesis, we
      expressed the mature form of human P450scc in Escherichia coli. The expression
      system enabled us to produce larger quantities of active cytochrome than have
      previously been isolated from placental mitochondria. The expressed P450scc was
      purified to near homogeneity and shown to have catalytic properties comparable to
      the enzyme purified from the human placenta. The mature form of human adrenodoxin
      was also expressed in E. coli and supported cholesterol side chain cleavage
      activity with the same Vmax as that observed using bovine adrenodoxin but with a
      higher Km. Mutation of Ile-462 to Leu in human P450scc caused a decrease in the
      catalytic rate constant (kcat) with cholesterol as substrate, increased the Km
      for 22R-hydroxycholesterol, but did not affect the kinetic constants for 20 alpha
      hydroxycholesterol. This suggests that Ile-462 lies close to the side chain
      binding site and that the side chains of cholesterol, 22R-hydroxycholesterol, and
      20 alpha-hydroxycholesterol occupy slightly different positions in the active
      site.

PMID- 9578607
TI  - Calculation of standard transformed Gibbs energies and standard transformed
      enthalpies of biochemical reactants.
AB  - The standard Gibbs energies of formation and standard enthalpies of formation of
      species involved in biochemical reactions are used to calculate standard
      transformed Gibbs energies of formation and standard transformed enthalpies of
      formation of 53 reactants (sums of species) at 298.15 K, pH 7, and ionic
      strengths of 0, 0.1, and 0. 25 M. The standard transformed Gibbs energies of
      formation are used to calculate apparent equilibrium constants K' for 22
      biochemical reactions for which apparent equilibrium constants have been
      determined close to these conditions. This comparison is generally satisfactory
      given the differences in experimental conditions. The transformed formation
      properties for the 53 reactants make it possible to calculate transformed
      formation properties for other reactants involved in biochemical reactions with
      some of these reactants. This is illustrated by calculating standard transformed
      Gibbs energies of formation for 11 more reactants without information on the
      standard Gibbs energies of formation of the species. The list of 64 reactants for
      which standard transformed Gibbs energies of formation are presented can be
      considerably extended. The use of tables of standard transformed Gibbs energies
      of formation to store information on apparent equilibrium constants is more
      efficient than simply storing apparent equilibrium constants because a reactant
      can be looked up in a table and may be involved in hundreds of reactions. The
      effects of magnesium ions on several reactions involving ATP are calculated. The
      advantages of using enzyme-catalyzed reactions for determining thermodynamic
      properties of complicated molecules in aqueous solution are discussed.

PMID- 9578608
TI  - Substrate selectivities and lipid modulation of plant phospholipase D alpha, 
      beta, and -gamma.
AB  - Three classes of phospholipase D (PLD), designated PLD alpha, -beta, and -gamma,
      have been cloned from plants, but their substrate selectivities have not been
      established. Using active PLDs expressed from their cDNAs in Escherichia coli, we
      compared the hydrolytic activities of these three PLDs toward various
      phospholipids and the influence of substrate composition on their substrate
      selectivities. When single-class phospholipid vesicles of phosphatidylcholine
      (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG),
      phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylinositol 4,5
      bisphosphate (PIP2), N-acylphosphatidylethanolamine (NAPE), and cardiolipin (CL)
      were examined, PLD alpha hydrolyzed PC, PE, and PG but PLD beta and -gamma showed
      no activity toward any of these lipids. When PIP2 was included in mixed vesicles
      with the phospholipids above, PLD alpha showed the same PC-, PE-, and PG
      hydrolyzing ability, whereas PLD beta and -gamma were able to hydrolyze both PE
      and PS. When both PE and PIP2 were included in substrate vesicles, PLD beta and
      PLD gamma hydrolyzed PC, PG, and NAPE, showing that both PE and PIP2 are required
      for PC, PG, and NAPE hydrolysis by PLD beta and -gamma. The PE activation of PLD
      beta and -gamma required lipid vesicles made of mostly PE, suggesting that PE may
      affect the substrate presentation rather than serve as a cofactor of these PLDs.
      Under equivalent reaction conditions, PLD beta displayed a similar preference for
      PC and NAPE, whereas PLD gamma preferred NAPE to PC by nearly three times. None
      of the three PLDs used PI, CL, or PIP2 as substrates. These results have
      identified PS- and NAPE-hydrolyzing PLDs and have indicated an important role for
      lipid composition in regulating the substrate selectivity of PLD beta and -gamma.

PMID- 9578609
TI  - Effects of ionic strength and chloride ion on activities of the glucose-6
      phosphatase system: regulation of the biosynthetic activity of glucose-6
      phosphatase by chloride ion inhibition/deinhibition.
AB  - Certain amino acids stimulate glycogenesis from glucose. The regulatory volume
      decrease mechanism explaining these effects was defined by Meijer et al. (1992,
      J. Biol. Chem. 267, 5823-5828). It involves amino acid-induced swelling of
      hepatocytes resulting in loss of chloride ions which leads to deinhibition of
      glycogen synthase phosphatase. This results in enhanced conversion of the
      inactive to active form of glycogen synthase and thus enhanced glycogen
      synthesis. We have studied the effects of amino acids and chloride ion on the
      glucose-6-phosphatase system (Glc-6-Pase) with rat liver microsomal preparations,
      and correlated our results with those reported by others with glycogen synthase.
      Glc-6-Pase activities are increased by elevated ionic strength varied by
      increasing the concentration of various buffers or charged amino acids but are
      not affected by changes in osmolarity, varied with disaccharides or uncharged
      amino acids. With undisrupted microsomes, chloride ion competitively inhibits
      carbamyl phosphate: glucose phosphotransferase (KCP,t,UMi,Cl- = 19 mM) more
      extensively than Glc-6-P phosphohydrolase (KG6P,h,UMi,Cl- = 117 mM). Inhibition
      by chloride ion and activation due to ionic strength may be important
      considerations when assessing in vitro Glc-6-Pase activities where an attempt is
      made to replicate physiologic conditions. Further we propose that amino acids may
      play a role in increasing biosynthetic activity of Glc-6-Pase, as well as
      previously characterized glycogen synthase (Meijer et al., op. cit.), via the
      regulatory volume decrease mechanism through diminished chloride ion inhibition.
      Reduced concentration of chloride ion will (1) deinhibit the biosynthetic
      activity of Glc-6-Pase, while still inhibiting Glc-6-P hydrolysis, leading to an
      increased cellular concentration of Glc-6-P (an important glycogenic intermediate
      as well as allosteric activator of glycogen synthase) and (2) increase the active
      form of glycogen synthase by deinhibiting glycogen synthase phosphatase both
      through the previously defined mechanism (see above) and via Glc-6-P-enhanced
      conversion of glycogen synthase from its inactive to active form. We propose that
      the biosynthetic activity of Glc-6-Pase may act in concert with glycogen synthase
      during amino acid-induced glycogenesis from glucose.

PMID- 9578610
TI  - Site-directed mutagenesis of a regulatory site of Escherichia coli ADP-glucose
      pyrophosphorylase: the role of residue 336 in allosteric behavior.
AB  - Site-directed mutagenesis was used to probe the role of glycine residue 336 in
      the regulatory properties of Escherichia coli ADP-glucose pyrophosphorylase. This
      residue was previously found to be changed from glycine to aspartate in the gene
      of an Escherichia coli mutant strain. The mutant enzyme had altered kinetic
      properties, including higher activity in the absence of the activator fructose
      1,6-bisphosphate (FBP), higher apparent affinity for FBP and substrates, and
      lower apparent affinity for the inhibitor AMP. The observed changes in activity
      were caused by this single mutation, because the aspartate mutant was prepared
      from the wild-type gene. The kinetic properties of the site-directed mutant are
      identical to those of the enzyme from the mutant strain. A series of mutants was
      prepared to explore the effects of charge, size, shape, and hydrophobicity of the
      amino acid at residue 336 on the enzyme regulatory properties. All of the
      mutants, except for the lysine and arginine enzymes, were expressed and purified
      for kinetic analysis. The glycine-336 residue is able to tolerate diverse
      substitutions without compromise of catalytic activity. A range of allosteric
      changes was observed, with the most dramatic effects seen with the highly active
      aspartate enzyme and the low-activity G336Q mutant, which exhibited lower
      apparent affinities for activator and substrates and higher apparent affinity for
      inhibitor. The altered allosteric properties of the G336D mutant enzyme were
      almost completely abolished by substitution of asparagine. Thus, the aspartate
      negative charge is essential for the altered binding of effectors.

PMID- 9578612
TI  - Control analysis of muscle glycogen metabolism.
AB  - A minimal model of glycogen metabolism in muscle tissue is analyzed in accordance
      with metabolic control analysis. The model contains two branch points. Rather
      than contributing to complexity of the analysis, this branching allows expression
      of the control coefficients in a simplified form. Glucose 6-phosphate is the
      metabolite at the first branch point, and the analysis is simplified further by
      the fact that glucose 6-phosphate is the substrate for enzymes which catalyze
      near-equilibrium reactions. Control of the concentration of glucose 6-phosphate
      is of interest because of its pivotal location in the metabolic system, but also
      because it interacts with an allosteric site on glycogen synthase to stimulate
      glycogen synthase activity. It is shown that the control which the transporter
      and enzymes involved in glycogen synthesis exert on glycolytic flux is
      proportional to the control which these components exert on glucose 6-phosphate
      concentration. Thus, glycolysis plays a major role in control of glucose 6
      phosphate concentration. It is concluded that control of glycogen synthesis is
      not a rigid parameter of any component of this metabolic system. Rather the
      distribution of control is flexible and shifts from one portion of the system to
      another in response to shifts in the physiological state. An important element in
      determining the distribution of control of glycogen synthesis is the change in
      the sensitivity of the allosteric site of glycogen synthase to glucose 6
      phosphate which is brought about by conversion of glycogen synthase to the
      dephosphorylated, glucose 6-phosphate-independent, state.

PMID- 9578611
TI  - Comparison of formation of D2/E2-isoprostanes and F2-isoprostanes in vitro and in
      vivo--effects of oxygen tension and glutathione.
AB  - The isoprostanes (IsoPs) are bioactive prostaglandin-like compounds derived from
      the free-radical-catalyzed peroxidation of arachidonic acid in vitro and in vivo.
      IsoPs possessing either an F-type prostane ring (F2-IsoPs) or D/E-type prostane
      rings (D2/E2-IsoPs) are formed depending on whether IsoP endoperoxide
      intermediates undergo reduction or isomerization, respectively. Little, however,
      is known regarding factors influencing the formation of various classes of IsoPs,
      particularly D2/E2-IsoPs. Thus, studies were undertaken to examine the formation
      of D2/E2-IsoPs in relation to F2-Isops both in vitro and in vivo. In peroxidizing
      rat liver microsomes, the formation of D2/E2-IsoPs increased in a time- and
      oxygen-dependent manner and correlated with F2-IsoP generation and loss of
      precursor arachidonic acid, although the absolute amount of D2/E2-IsoPs formed
      exceeded by over 5-fold the levels of F2-IsoPs formed. Surprisingly, however, in
      liver tissue from rats exposed to an oxidant stress, levels of F2-IsoPs were up
      to 10-fold greater than those of D2/E2-IsoPs, suggesting that an endogenous
      process causes IsoP endoperoxide reduction in vivo. Addition of glutathione (GSH)
      to peroxidizing microsomes at concentrations from 0.01 to 5 mM increased the
      formation of F2-IsoPs at the expense of D2/E2-IsoPs. Boiling of microsomes did
      not alter the effect of GSH. Formation of D2/E2-IsoPs in liver tissue in vivo was
      greatly enhanced compared to F2-IsoPs in rats depleted of GSH. Thus, GSH
      modulates the formation of different classes of IsoPs in vitro and in vivo. Other
      thiols, including beta-mercaptoethanol, dithiothreitol, and cysteine, were able
      to substitute for GSH. These studies indicate that GSH promotes F2-IsoP formation
      and diminishes D2/E2-IsoP levels in vitro and in vivo by causing reduction of
      IsoP endoperoxides.

PMID- 9578613
TI  - Molecular cloning, functional expression, and characterization of pyruvate
      dehydrogenase kinase from anaerobic muscle of the parasitic nematode Ascaris
      suum.
AB  - The pyruvate dehydrogenase complex (PDC) plays a key role in the anaerobic
      mitochondrial metabolism of the parasitic nematode Ascaris suum. A cDNA coding
      for an A. suum pyruvate dehydrogenase kinase (APDK) has been cloned and sequenced
      from poly(A)+ RNA isolated from adult A. suum muscle.2 APDK exhibited significant
      sequence identity to mammalian PDKs. Nucleotide sequence analysis of the APDK
      cDNA revealed a 22-nucleotide spliced leader, characteristic of many nematode
      mRNAs, a 5'-UTR of 6 nucleotides, an open reading frame of 1197 nucleotides, and
      a 3'-UTR of 101 nucleotides that included a putative polyadenylation signal. The
      open reading frame predicted a protein of 399 amino acids with a molecular weight
      of 45,402 that included a putative 18-aminoacid leader peptide. Recombinant APDK
      (rAPDK) was functionally expressed in Escherichia coli with a his tag at its N
      terminus and purified to apparent homogeneity on Ni-NTA-agarose. Recombinant APDK
      was a dimer and was not autophosphorylated and its activity was stimulated in the
      presence of APDK-deficient adult A. suum muscle PDC presumably by the binding of
      APDK to the dihydrolipoyl transacetylase (E2) core of the complex. After binding
      to the core, rAPDK activity was stimulated by elevated NADH/NAD+ and acetyl
      CoA/CoA ratios within the same ranges as observed for the native APDK.
      Immunoblotting suggested that native APDK focused as a series of 43-kDa spots (pI
      6.1-6.8) on two-dimensional gels of the purified adult A. suum muscle PDC.

PMID- 9578614
TI  - Involvement of thyroid hormone and its alpha receptor in avian neurulation.
AB  - We have analyzed the expression pattern of c-erb A alpha and c-erb A beta which
      encode the thyroid hormone receptors (T3R alpha and T3R beta) during early
      chicken embryogenesis. Only c-erb A alpha expression was detected by RT-PCR and
      whole-mount in situ hybridization. c-erb A alpha transcripts were found to be
      already present at low level in embryos before egg incubation. During neurulation
      a marked increase was observed in neurectoderm. A reporter cell line was then
      constructed and used to demonstrate the release of significant amount of thyroid
      hormone (T3) from egg yolk by area opaca cells before gastrulation. During
      gastrulation T3 was found to be enriched in the primitive streak and Hensen's
      node. Introduction of excess T3 frequently resulted in abnormal development of
      anterior structures, mainly neural tube defects and anencephalia. These
      observations suggest that T3R alpha, like the closely related retinoic acid
      receptors, fulfills functions which are important for embryonic development well
      before the onset of thyroid gland function.

PMID- 9578615
TI  - Ectopic expression of Msx-2 in posterior limb bud mesoderm impairs limb
      morphogenesis while inducing BMP-4 expression, inhibiting cell proliferation, and
      promoting apoptosis.
AB  - During early stages of chick limb development, the homeobox-containing gene Msx-2
      is expressed in the mesoderm at the anterior margin of the limb bud and in a
      discrete group of mesodermal cells at the midproximal posterior margin. These
      domains of Msx-2 expression roughly demarcate the anterior and posterior
      boundaries of the progress zone, the highly proliferating posterior mesodermal
      cells underneath the apical ectodermal ridge (AER) that give rise to the skeletal
      elements of the limb and associated structures. Later in development as the AER
      loses its activity, Msx-2 expression expands into the distal mesoderm and
      subsequently into the interdigital mesenchyme which demarcates the developing
      digits. The domains of Msx-2 expression exhibit considerably less proliferation
      than the cells of the progress zone and also encompass several regions of
      programmed cell death including the anterior and posterior necrotic zones and
      interdigital mesenchyme. We have thus suggested that Msx-2 may be in a regulatory
      network that delimits the progress zone by suppressing the morphogenesis of the
      regions of the limb mesoderm in which it is highly expressed. In the present
      study we show that ectopic expression of Msx-2 via a retroviral expression vector
      in the posterior mesoderm of the progress zone from the time of initial formation
      of the limb bud severely impairs limb morphogenesis. Msx-2-infected limbs are
      typically very narrow along the anteroposterior axis, are occasionally truncated,
      and exhibit alterations in the pattern of formation of skeletal elements,
      indicating that as a consequence of ectopic Msx-2 expression the morphogenesis of
      large portions of the posterior mesoderm has been suppressed. We further show
      that Msx-2 impairs limb morphogenesis by reducing cell proliferation and
      promoting apoptosis in the regions of the posterior mesoderm in which it is
      ectopically expressed. The domains of ectopic Msx-2 expression in the posterior
      mesoderm also exhibit ectopic expression of BMP-4, a secreted signaling molecule
      that is coexpressed with Msx-2 during normal limb development in the anterior
      limb mesoderm, the posterior necrotic zone, and interdigital mesenchyme. This
      indicates that Msx-2 regulates BMP-4 expression and that the suppressive effects
      of Msx-2 on limb morphogenesis might be mediated in part by BMP-4. These studies
      indicate that during normal limb development Msx-2 is a key component of a
      regulatory network that delimits the boundaries of the progress zone by
      suppressing the morphogenesis of the regions of the limb mesoderm in which it is
      highly expressed, thus restricting the outgrowth and formation of skeletal
      elements and associated structures to the progress zone. We also report that
      rather large numbers of apoptotic cells as well as proliferating cells are
      present throughout the AER during all stages of normal limb development we have
      examined, indicating that many of the cells of the AER are continuously
      undergoing programmed cell death at the same time that new AER cells are being
      generated by cell proliferation. Thus, a balance between cell proliferation and
      programmed cell death may play a very important role in maintaining the activity
      of the AER.

PMID- 9578616
TI  - Components of the signaling pathway linking the 1-methyladenine receptor to MPF
      activation and maturation in starfish oocytes.
AB  - Starfish oocytes are arrested at the G2/M-phase border of meiosis I. Exposure to
      their natural mitogen, 1-methyladenine (1-MA), leads to the activation of MPF and
      MAP kinase, resumption of the meiotic cell cycle, and fertilization competency.
      The 1-MA receptor has not yet been identified, but it is known to be linked
      functionally to a pertussis toxin-sensitive G-protein. G beta gamma appears to be
      the major effector of the 1-MA receptor, since injection of G beta gamma, but not
      activated G alpha i, leads to the activation of MPF, entry into meiosis, and
      oocyte maturation. The components that connect G beta gamma to MPF and MAP kinase
      activation in oocytes are unknown. In mammalian cells, a novel
      phosphatidylinositol 3-kinase, PI-3 kinase-gamma, links G beta gamma to the MAP
      kinase activation pathway. Here we show that PI-3 kinase is required for starfish
      oocyte maturation. LY294002 and wortmannin, inhibitors of PI-3 kinase, block MPF
      and MAP kinase activation and entry into meiosis. Inhibition by LY294002 is
      reversible and limited to the hormone-dependent period. Neither inhibitor,
      however, blocks the earliest hormone-induced event, formation of actin spikes at
      the cell membrane. By contrast, pertussis toxin blocks both actin spiking and
      later events, arguing that PI-3 kinase functions downstream of G beta gamma.
      Finally, we show that unlike the well-studied case in Xenopus oocytes, where MAP
      kinase is an essential component of the MPF activation pathway, MAP kinase is not
      required for either MPF activation or subsequent oocyte maturation in starfish.
      Instead, its major role appears to be suppression of DNA synthesis in
      unfertilized, haploid eggs.

PMID- 9578618
TI  - Cell-intrinsic timers and thyroid hormone regulate the probability of cell-cycle
      withdrawal and differentiation of oligodendrocyte precursor cells.
AB  - During vertebrate development many types of precursor cells divide a limited
      number of times before they stop dividing and terminally differentiate. It is
      unclear what causes the cells to stop dividing when they do. We have been
      studying this problem in the oligodendrocyte cell lineage, which is responsible
      for myelination in the vertebrate central nervous system. Here we show for the
      first time that in clonal cultures of oligodendrocyte precursor cells purified
      from embryonic day 18 (E18) rat optic nerves the first oligodendrocytes develop
      within 3-4 days, equivalent to the time they first differentiate in the nerve,
      and that this timely differentiation depends on the presence of thyroid hormone.
      These findings suggest that a cell-intrinsic, thyroid-hormone-regulated timer
      determines when the first oligodendrocytes develop. Whereas the first
      oligodendrocytes develop asynchronously within clones, the vast majority develop
      after the first week in culture and do so more synchronously within clones. We
      show that beta1 thyroid hormone receptors in the precursor cells increase in
      clonal cultures in the absence of thyroid hormone in parallel with the increasing
      sensitivity of the cells to the cell-cycle-arresting activity of thyroid hormone;
      moreover, the increase in beta1 receptors, like the timer itself, is accelerated
      at 33 degrees C compared to 37 degrees C, suggesting that the increase in
      receptors may be part of the intrinsic timer. Finally, we show that the precursor
      cells do not divide indefinitely when stimulated to divide extensively in the
      absence of thyroid hormone but, instead, eventually stop dividing and either die
      or differentiate.

PMID- 9578617
TI  - In vivo regulation of cyclin A/Cdc2 and cyclin B/Cdc2 through meiotic and early
      cleavage cycles in starfish.
AB  - In starfish, fertilization occurs naturally at late meiosis I. In the absence of
      fertilization, however, oocytes complete meiosis I and II, resulting in mature
      eggs arrested at the pronucleus stage, which are still fertilizable. In this
      study, we isolated cDNAs of starfish cyclin A and Cdc2, and monitored extensively
      the cell cycle dynamics of cyclin A and cyclin B levels and their associated Cdc2
      kinase activity, Tyr phosphorylation of Cdc2, and Cdc25 phosphorylation states
      throughout meiotic and early embryonic cleavage cycles in vivo. In meiosis I,
      cyclin A was undetectable and cyclin B/Cdc2 alone exhibited histone H1 kinase
      activity, while thereafter both cyclin A/Cdc2 and cyclin B/Cdc2 kinase activity
      oscillated along with the cell cycle. Cyclin B-, but not cyclin A-, associated
      Cdc2 was subjected to regulation via Tyr phosphorylation, and phosphorylation
      states of Cdc25 correlated with cyclin B/Cdc2 kinase activity with some
      exceptions. Between meiosis I and II and at the pronucleus stage, cyclin A and B
      levels remained low, Cdc2 Tyr phosphorylation was undetectable, and Cdc25
      remained phosphorylated depending on MAP kinase activity, showing a good
      correlation between these two stages. Upon fertilization of mature eggs, Cdc2 Tyr
      phosphorylation reappeared and Cdc25 was dephosphorylated. In the first cleavage
      cycle, under conditions which prevented Cdc25 activity, cyclin A/Cdc2 was
      activated with a normal time course and then cyclin B/Cdc2 was activated with a
      significant delay, resulting in the delayed completion of M-phase. Thus, in
      contrast to meiosis I, both cyclin A and cyclin B appear to be involved in the
      embryonic cleavage cycles. We propose that regulation of cyclin A/Cdc2 and cyclin
      B/Cdc2 is characteristic of meiotic and early cleavage cycles.

PMID- 9578619
TI  - Molecular cloning and characterization of meichroacidin (male meiotic metaphase
      chromosome-associated acidic protein).
AB  - We have isolated a cDNA clone encoding a germ cell specific protein from an
      expression cDNA library prepared from the mouse testis, using testis-specific
      polyclonal antibodies. Sequence analysis of the cDNA revealed that the deduced
      amino acid sequence consisted of 284 residues, including a nominal repeat
      structure in the N-terminal region. Northern blot analysis revealed the presence
      of a transcript of 1.3 kb exclusively expressed in the testis and ovary, but at
      relatively low levels in the ovary. In contrast, no other tissues and organs
      expressed significant levels of the transcript. Expression of the mRNA in the
      testis was first detected on day 14 in postnatal development. Western blot
      analysis showed the presence of the protein with a molecular weight of
      approximately 40 kDa and an isoelectric point of 4.9. The protein was exclusively
      found in the testis and ovary, but in a far lesser amount in the ovary as was the
      case with the transcript. Immunohistochemical examination revealed that the
      protein was predominantly present in the cytoplasm in pachytene spermatocytes
      through to round spermatids. However, during the disappearance of the nuclear
      envelope at both the first and second meiotic divisions, the protein was
      localized around the metaphase chromosomes and spindles. Because of this, the
      name meichroacidin which stands for male meiotic metaphase chromosome-associated
      acidic protein is proposed for this antigen. The highly regulated stage-specific
      expression of meichroacidin and its specific association with the metaphase
      chromosomes and spindles suggest that the protein plays important roles in male
      meiosis.

PMID- 9578620
TI  - Na/K-ATPase-mediated 86Rb+ uptake and asymmetrical trophectoderm localization of
      alpha1 and alpha3 Na/K-ATPase isoforms during bovine preattachment development.
AB  - This study evaluated Na/K-ATPase alpha 1- and alpha 3-subunit isoform polypeptide
      expression and localization during bovine preattachment development. Na/K-ATPase
      cation transport activity from the one-cell to blastocyst stage was also
      determined by measuring ouabain-sensitive 86Rb+ uptake. Both alpha1- and alpha 3
      subunit polypeptides were detected by immunofluorescence to encircle the entire
      cell margins of each blastomere of inseminated zygotes, cleavage stage embryos,
      and morulae. Immunofluorescent localization of alpha1-subunit polypeptide in
      bovine blastocysts revealed an alpha1 immunofluorescence signal confined to the
      basolateral membrane margins of the trophectoderm and encircling the cell
      periphery of each inner cell mass (ICM) cell. In contrast, alpha 3-subunit
      polypeptide immunofluorescence was localized primarily to the apical cell
      surfaces of the trophectoderm with a reduced signal present in basolateral
      trophectoderm regions. There was no apparent alpha 3-subunit signal in the ICM.
      Analysis of 86Rb+ transport in vitro demonstrated ouabain-sensitive activity
      throughout development from the one-cell to the six- to eight-cell stage of
      bovine development. 86Rb+ uptake by morulae (day 6 postinsemination) did not vary
      significantly from uptake detected in cleavage stage embryos; however, a
      significant increase was measured at the blastocyst stage (P < 0.05). Treatment
      of embryos with cytochalasin D (5 micrograms/ml) did not influence 86Rb+ uptake
      in cleavage stage embryos. Cytochalasin D treatment however was associated with a
      significant rise in ion transport in morulae and blastocysts (13.49 and 61.57
      fmol/embryo/min, respectively) compared to untreated controls (2.65 and 22.83
      fmol/embryo/min, respectively). Our results, for the first time, demonstrate that
      multiple Na/K-ATPase alpha-subunit isoforms are distributed throughout the first
      week of mammalian development and raise the possibility that multiple isozymes of
      the Na/K-ATPase contribute to blastocyst formation.

PMID- 9578621
TI  - GDNF and ET-3 differentially modulate the numbers of avian enteric neural crest
      cells and enteric neurons in vitro.
AB  - Vagal (hindbrain) neural crest cells migrate rostrocaudally in the gut to
      establish the enteric nervous system. Glial-derived neurotrophic factor (GDNF)
      and its receptor(s), and endothelin-3 (ET-3) and its receptor, are crucial for
      enteric nervous system development. Mutations interrupting either of these
      signaling pathways cause aganglionosis in the gut, termed Hirschsprung's disease
      in humans. However, the precise functions of GDNF and ET-3 in enteric
      neurogenesis are still unknown. We isolated precursor cells of the enteric
      nervous system from the vagal level neural crest of E1.7 quail embryos prior to
      entry into the gut and from the developing midgut at stages corresponding to
      migrating (E4.7) and longer resident differentiating cells (E7) using HNK-1
      immunoaffinity and magnetic beads. These cells were tested for their response to
      GDNF and ET-3 in culture. ET-3 and GDNF had little effect in vitro on the growth,
      survival, migration, or neurogenesis of E1.7 vagal neural crest cells. In
      contrast, GDNF increased the proliferation rate and numbers of enteric neural
      precursors isolated from the E4.7 and E7 gut. Also, many more neurons and
      neurites developed in cultures treated with GDNF, disproportionately greater than
      the effect on cell numbers. At high cell density and in the presence of serum, ET
      3, and GDNF had an additive effect on proliferation of neuron precursor cells. In
      defined medium, or low cell density, ET-3 reduced cell proliferation, overriding
      the proliferative effect of GDNF. Regardless of the culture condition, the
      stimulatory effect of GDNF on neuron numbers was strikingly diminished by the
      simultaneous presence of ET-3. We propose first that GDNF promotes the
      proliferation in the migratory enteric neural precursor cell population once the
      cells have entered the gut and is especially crucial for the differentiation of
      these cells into nonmigrating, nonproliferating enteric neurons. Second, we
      suggest that ET-3 modulates the action of GDNF, inhibiting neuronal
      differentiation to maintain the precursor cell pool, so ensuring sufficient
      population numbers to construct the entire enteric nervous system. Third, we
      suggest that generalized defects in enteric neural precursor cell numbers and
      differentiation due to mutations in the ET-3 and GDNF systems are converted to
      distal gut neural deficiencies by the rostrocaudal migration pattern of the
      precursors. Fourth, we suggest that additional factors such as those found in
      serum and produced by the enteric neural cells themselves are likely also to be
      involved in enteric nervous system development and consequently in Hirschsprung's
      disease.

PMID- 9578622
TI  - Multiple elements regulate Mash1 expression in the developing CNS.
AB  - Mash1, a transcription factor of the basic helix-loop-helix class, is expressed
      during embryogenesis in restricted regions of the nervous system. An essential
      role for Mash1 in neural development was demonstrated previously in mice carrying
      a targeted disruption of the Mash1 gene. Regulation of the precise temporal and
      spatial expression of Mash1 is thus likely to be important for proper neural
      development. In this study, sequences that regulate Mash1 expression in the
      central nervous system were characterized by assaying the expression of lacZ
      reporter genes in transgenic embryos. A 1158-bp enhancer localized approximately
      7 kb upstream of the Mash1 coding region was identified. Deletions within this
      enhancer region reveal the presence of both positive and negative cis-acting
      elements. Analysis of multiple sequences within the enhancer demonstrate that
      different elements preferentially function in different regions within the Mash1
      specific CNS expression domain. In addition, a role for sequences 3' of the Mash1
      coding region is revealed, providing evidence for posttranscriptional control of
      Mash1 expression in multiple CNS domains.

PMID- 9578623
TI  - Switching of chemoattractant receptors programs development and morphogenesis in
      Dictyostelium: receptor subtypes activate common responses at different agonist
      concentrations.
AB  - One of the common functional features among G-protein coupled receptors is the
      occurrence of multiple subtypes involved in similar signal transduction events.
      The cAMP chemoattractant receptor family of Dictyostelium discoideum is composed
      of four receptors (cAR1-cAR4), which are expressed sequentially throughout the
      developmental transition from a unicellular to a multicellular organism. The
      receptors differ in affinity for cAMP and in the sequences of their C-terminal
      domains. In this study, we constitutively expressed cAR1, cAR2, and cAR3 as well
      as a series of chimeric and mutant receptors and assessed the capacity of each to
      mediate chemotaxis, activation of adenylyl cyclase and actin polymerization, and
      rescue the developmental defect of car1-/car3- cells. We found that various
      receptors and mutants sense different concentration ranges of cAMP but all can
      mediate identical responses during the aggregation stage of development. The
      responses displayed very similar kinetics, suggesting no major differences in
      regulatory properties attributable to the C-terminal domains. We speculate that
      switching of receptor subtypes during development enables the organism to respond
      to the changing concentrations of the chemoattractant and thereby program
      morphogenesis appropriately.

PMID- 9578624
TI  - Growth promoting activity of oocytes on granulosa cells is decreased upon meiotic
      maturation.
AB  - An increasing body of evidence indicates that the oocyte plays an active role in
      the control of ovarian follicle development in mammals. In the present study, we
      have examined the role of oocytes in regulating granulosa cell proliferation. Rat
      and bovine oocytes cocultured with rat granulosa cells stimulated granulosa cell
      DNA synthesis and DNA content in the cultures. FSH or cAMP further amplified this
      effect. Poor-quality oocytes showed a marked decrease in their stimulatory
      effect. Stimulation of DNA synthesis by bovine oocytes seems to be cell-type
      specific, since Swiss 3T3 fibroblasts and CCL-64 mink lung epithelial cells were
      not responsive, while primary cultures of rat and bovine granulosa cells and the
      bovine granulosa cell line BGC-1 showed significant responses. Oocyte-conditioned
      medium produced only a slight stimulation of rat granulosa cell DNA synthesis.
      However, the effect of oocyte coculture was dependent on the total incubation
      volume, suggesting that the growth promoting activity was mediated by a soluble
      factor. The stimulation elicited by bovine oocytes was evident even in the
      presence of maximally effective doses of transforming growth factor-beta or tumor
      necrosis factor-alpha, indicating that neither of these growth factors was
      responsible for this effect. In vitro maturation of bovine oocytes was associated
      with a marked decrease in the stimulatory activity. This decrease was partially
      prevented when maturation was blocked by addition of cycloheximide. Comparison of
      the developmental pattern of the secretion of the growth promoting activity with
      that of the cumulus expansion-enabling factor indicated that both activities can
      be dissociated. Our data suggest the existence of a very labile factor produced
      by the oocyte before completion of the first meiotic division that promotes
      granulosa cell proliferation.

PMID- 9578625
TI  - Posttranscriptional control of gene expression in filamentous fungi.

PMID- 9578626
TI  - The ipiO gene of Phytophthora infestans is highly expressed in invading hyphae
      during infection.
AB  - The expression of the in planta-induced gene ipiO of the potato late blight
      pathogen Phytophthora infestans was analyzed during various developmental stages
      of its life cycle. ipiO mRNA was detected in zoospores, cysts, germinating cysts,
      and young mycelia, but not in sporangia or in old mycelia grown in vitro. ipiO is
      not only expressed in stages prior to infection but also during colonization of
      potato and tomato leaves. In disease lesions, ipiO mRNA was detected in the water
      soaked area and the healthy-looking plant tissue surrounding it. In contrast,
      ipiO mRNA was not found in necrotized tissue or in sporulating areas of a lesion.
      To determine more precisely the location and time of ipiO gene expression in
      planta, cytological assays were performed using a P. infestans transformant
      expressing a transcriptional fusion between the ipiO1 promoter and the beta
      glucuronidase (GUS) reporter gene. GUS staining was found specifically in the
      subapical and vacuolated area of tips of invading hyphae. The histochemical GUS
      assays demonstrate that ipiO is expressed during biotrophic stages of the disease
      cycle.

PMID- 9578627
TI  - Random association among alleles in clonal populations of Sclerotinia
      sclerotiorum.
AB  - Multiple loci identified in DNA fingerprints were used to test for random
      association in two agricultural populations of S. sclerotiorum. In linkage
      disequilibrium tests among pairs of loci with frequencies between 0.1 and 0.9,
      44.5 and 80.5% of pairs of loci were consistent with random association in the
      clone-corrected samples of the Canadian canola and the North Carolina cabbage
      populations, respectively. In estimates of corrected (Bonferroni) P value, 70.66
      and 98.89% of pairs of loci were in random association. All four possible
      genotypes for each pair of loci were observed in the Canadian canola sample,
      consistent with random association among loci. In multilocus association tests
      across all loci, however, significant association was observed in both
      populations. In the Canadian canola population, 40 possible heterokaryons were
      identified. Our data suggest that populations of S. sclerotiorum are
      predominantly clonal and that occasional genetic exchange and recombination, and
      not mutation alone, may be a source of new genotypes.

PMID- 9578628
TI  - Positioning of nuclei in the secondary Mycelium of Schizophyllum commune in
      relation to differential gene expression.
AB  - In this paper we propose a novel type of gene regulation in the MATA|l4 MATB|l4
      heterokaryon of Schizophyllum commune by means of differential positioning of the
      nuclei. It was found that binucleate hyphae with juxtaposed nuclei secrete SC4
      hydrophobin (abundant during fruit-body formation), while SC3 (abundant during
      aerial hyphae formation in both mono- and dikaryons) appeared to be absent.
      Certain growth conditions disrupted the binucleate state in that the compatible
      nuclei became separated at a considerable distance. Under these conditions SC4
      was not secreted while SC3 was secreted to a high degree. Disruption of the
      binucleate state was earlier observed in developing aerial hyphae which secrete
      SC3. Apparently, when the nuclei are in close proximity the dikaryon-expressed
      genes are switched on by interaction of the products of the MATA and MATB mating
      type genes, while SC3 is suppressed by interacting products of the MATB genes, as
      occurs in the common MATA heterokaryon (MATA= MATB|l4). Growth conditions that
      lead to disruption of the binucleate state apparently result in abolishment of
      interaction between the MATB mating-type genes. Under these conditions, dikaryon
      specific mRNAs do not accumulate in the MATA|l4 MATB|l4 heterokaryon, while SC3
      mRNA becomes highly abundant.

PMID- 9578629
TI  - Optional introns in mitochondrial DNA of Podospora anserina are the primary
      source of observed size polymorphisms.
AB  - The significant differences in mitochondrial genome size among seven races (B, E,
      M, T, U, W, and Y) of Podospora anserina have been found to be primarily due to
      the presence and/or absence of introns, including four introns not previously
      known to be optional. Information from physical mapping of races M and T, and
      sequence data from races A and s, was used to identify regions likely to contain
      insertions or deletions, which were then characterized using PCR and sequence
      analysis. Newly confirmed optional introns are the first intron of the large
      ribosomal RNA (LSUr1), the single intron of NADH dehydrogenase subunit 3 (ND3i1),
      the single intron in ATPase subunit 6 (ATPase6), and the fifth intron of
      cytochrome oxidase subunit I (COIi5). We have also found that race M exists in
      two forms as determined by mitochondrial DNA. These results bring to nine
      (including races A and s) the number of races characterized by mitochondrial
      intron content with a total of six known optional introns and one optional
      insertion. Eight of the nine races contain a distinct set of introns, providing a
      more reliable means for identification and comparison. The identification of
      optional mitochondrial introns in P. anserina may have evolutionary implications
      regarding the transfer and/or mobility of these introns.

PMID- 9578631
TI  - Evidence for PPC1, a determinant of the pilei-pellis color of Agaricus bisporus
      fruitbodies.
AB  - In the present study, we investigated the genetic basis of mushroom cap color. In
      first generation hybrids between a brown isolate and the white commercial hybrid
      U 1, the white trait was recessive. Color was determined using color meter
      technology in second generation hybrids obtained by crossing the homokaryotic
      progeny of a first generation hybrid with a homokaryon from U 1. Statistical
      analysis revealed a bimodal distribution describing two classes of white and not
      white hybrids. We postulate that a recessive allele at a single locus (PPC1)
      encodes the white pilei-pellis color. Joint segregation analyses indicated that
      PPC1 was linked to the ADH (alcohol dehydrogenase) locus. Through the analysis of
      the heterokaryotic progeny of the first generation hybrid, a recombination model
      is proposed in which PPC1 is located between the centromere and the ADH locus.

PMID- 9578630
TI  - Repeat-induced point mutations in Pad-1, a putative RNA splicing factor from
      Neurospora crassa, confer dominant lethal effects on ascus development.
AB  - We describe the characterization of a gene, Pad-1, from Neurospora crassa which
      displays sequence characteristics of the RS class of hnRNA-binding proteins
      (hnRNP) and mRNA splicing factors. This is the first report of the isolation of a
      putative hnRNP gene from N. crassa. PAD-1 showed 30% identity and 57% similarity
      to a protein, HCC1, which was isolated using autoantibodies from patients
      suffering from hepatocellular carcinoma. Both HCC1 and PAD-1 show amino acid
      sequence similarities to the human splicing factor, U2AF65. Mutations induced in
      Pad-1 by repeat-induced point (RIP) mutation show dominant effects on ascus and
      ascospore formation, a novel phenotypic class of RIP mutants. A mutant isolated
      from the Pad-1 RIP cross displayed a severe vegetative growth defect and dominant
      effects on ascus development, indicating that Pad-1 is essential for both asexual
      and sexual development.

PMID- 9578632
TI  - Transformation-mediated developmental mutants of Glomerella graminicola.
AB  - Glomerella graminicola transformants were generated by insertional plasmid
      mutagenesis. Five transformants with developmental mutant phenotypes that
      segregated in crosses as single-gene mutations were selected. In four
      transformants, the mutant phenotype cosegregated with the inserted plasmid DNA.
      At least three of the mutants result from gene disruption, as demonstrated by
      recovery of the mutant phenotypes after transformation of wild type with
      "rescued" plasmid DNA. Whereas the wild type produces uninucleate, salmon-colored
      conidia, the tagged mutant M26 has white conidia. After exposure to either UV
      light or singlet oxygen, the percentage germination of M26 conidia is reduced
      compared to that of the wild-type conidia, indicating that the spore pigment
      confers protection from UV light and singlet oxygen. The tagged mutant T30 has
      weakened walls; falcate conidia rupture and hyphae have swollen regions unless
      the medium is amended with an osmoticum. The tagged mutant T29 has falcate
      conidia with one to four nuclei; wild-type falcate conidia are uninucleate. Two
      other mutants, one which grows slowly and one having conidia with increased
      curvature, are also described.

PMID- 9578633
TI  - Caspases: key mediators of apoptosis.
AB  - Recent studies have established that members of the caspase protease family are
      essential components of a conserved cell death program. Insights into their
      biological roles, structure and mechanism are enabling investigators to begin to
      explore the therapeutic potential of caspase inhibition.

PMID- 9578634
TI  - Scission of DNA at a preselected sequence using a single-strand-specific chemical
      nuclease.
AB  - BACKGROUND: We were interested in developing a protocol for cleaving large DNAs
      specifically. Previous attempts to develop such methods have failed to work
      because of high levels of nonspecific background scission. RESULTS: R-loop
      formation was chosen for sequence-specific targeting, a method of hybridization
      whereby an RNA displaces a DNA strand of identical sequence in 70% formamide
      using Watson-Crick base-pairing, leading to a three-stranded structure. R-loops
      are stabilized in aqueous solution by modifying the bases with chemical reagents.
      The R-loop was cleaved using a novel nuclease prepared from the Thr48-->Cys
      mutant of the single-strand-specific M-13 gene V protein (GVP), which was
      alkylated with 5-(iodoacetamido-beta-alanyl)1,10-phenanthroline. The cleavage
      products of the pGEM plasmid were cloned in to the pCR 2.1-TOPO vector.
      Adenovirus 2 DNA (35.8 kb; tenfold larger than the pGEM plasmid) was also cleaved
      quantitatively at a preselected sequence. CONCLUSIONS: A new method for cleaving
      duplex DNA at any preselected sequence was developed. The cleavage method relies
      on the chemical conversion of M-13 GVP into a nuclease, reflecting GVP's
      specificity for single-stranded DNA. The GVP chimera is the first example of a
      semisynthetic secondary structure specific nuclease. The chemical nuclease
      activity of 1,10-phenanthroline-copper is uniquely suited to this technique
      because it oxidizes the deoxyribose moiety without generating diffusible
      intermediates, providing clonable DNA fragments. The protocol could be useful in
      generating large DNA fragments for mapping the contiguity of probes or defining
      the exon-intron structure of transcription units.

PMID- 9578635
TI  - Probing the phosphoinositide 4,5-bisphosphate binding site of human profilin I.
AB  - BACKGROUND: Profilin is a widely and highly expressed 14 kDa protein that binds
      actin monomers, poly(L-proline) and polyphosphoinositol lipids. It participates
      in regulating actin-filament dynamics that are essential for many types of cell
      motility. We sought to investigate the site of interaction of profilin with
      phosphoinositides. RESULTS: Human profilin I was covalently modified using three
      tritium-labeled 4-benzoyldihydrocinnamoyl (BZDC)-containing photoaffinity analogs
      of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). The P-1-tethered D
      myoinositol 1,4,5-trisphosphate (Ins(1,4,5)P3) modified profilin I efficiently
      and specifically; the covalent labeling could be displaced by co-incubation with
      an excess of PtdIns(4,5)P2 but not with Ins(1,4,5)P3. The acyl-modified
      PtdIns(4,5)P2 analog showed little protein labeling even at very low
      concentrations, whereas the head-group-modified PtdIns(4,5)P2 phosphotriester
      labeled monomeric and oligomeric profilin. Mass spectroscopic analyses of CNBr
      digests of [3H]BZDC-Ins(1,4,5)P3-modified recombinant profilin suggested that
      modification was in the amino-terminal helical CNBr fragment. Edman degradation
      confirmed Ala1 of profilin I (residue 4 of the recombinant protein) was modified.
      Molecular models show a minimum energy conformation in which the hydrophobic
      region of the ligand contacts the amino-terminal helix whereas the 4,5
      bisphosphate interacts with Arg135 and Arg136 of the carboxy-terminal helix.
      CONCLUSIONS: The PtdIns(4,5)P2-binding site of profilin I includes a bisphosphate
      interaction with a base-rich motif in the carboxy-terminal helix and contact
      between the lipid moiety of PtdIns(4,5)P2 and a hydrophobic region of the
      aminoterminal helix of profilin. This is the first direct evidence for a site of
      interaction of the lipid moiety of a phosphoinositide bisphosphate analog with
      profilin.

PMID- 9578636
TI  - A ligand-mediated dimerization mode for vancomycin.
AB  - BACKGROUND: Vancomycin and related glycopeptide antibiotics exert their
      antimicrobial effect by binding to carboxy-terminal peptide targets in the
      bacterial cell wall and preventing the biosynthesis of peptidoglycan. Bacteria
      can resist the action of these agents by replacing the peptide targets with
      depsipeptides. Rational efforts to design new agents effective against resistant
      bacteria require a thorough understanding of the structural determinants of
      peptide recognition by vancomycin. RESULTS: The crystal structure of vancomycin
      in complex with N-acetyl-D-alanine has been determined at atomic resolution. Two
      different oligomeric interactions are seen in the structure: back-to-back dimers,
      as previously described for the vancomycin-acetate complex, and novel face-to
      face dimers, mediated largely by the bound ligands. Models of longer, naturally
      occurring peptide ligands may be built by extension of N-acetyl-D-alanine. These
      larger ligands can form an extensive array of polar and nonpolar interactions
      with two vancomycin monomers in the face-to-face configuration. CONCLUSIONS: A
      new dimeric form of vancomycin has been found in which two monomers are related
      in a face-to-face configuration, and bound ligands comprise a large portion of
      the dimer interface. The relative importance of face-to-face and back-to-back
      dimers to the antimicrobial activity of vancomycin remains to be established, but
      face-to-face interactions appear to explain how increased antimicrobial activity
      may arise in covalent vancomycin dimers.

PMID- 9578638
TI  - Elsewhere in biology

PMID- 9578637
TI  - Stretching exercises--flexibility in dihydrofolate reductase catalysis.
AB  - As an enzyme, dihydrofolate reductase performs two tasks: transformation of its
      substrate dihydrofolate or folate to tetrahydrofolate, using NADPH as a cofactor,
      and regeneration of the enzyme for a subsequent round of catalysis. Studies
      discussed in this review highlight the role of conformational flexibility in both
      of these enzymatic functions.

PMID- 9578639
TI  - The next chip-based revolution. Caliper Technologies Corp.

PMID- 9578640
TI  - That's an order.

PMID- 9578641
TI  - [p53 mutations and chemoresistance in oromaxillofacial squamous-cell carcinomas.
      The results of a molecular genetics study of p53 in metastatic oromaxillofacial
      tumors and an evaluation of the response to neoadjuvant chemotherapeutic
      treatment].
AB  - MATERIAL AND METHODS: The authors carried out a p53 genetic research on native
      DNA in 15 oral-maxillofacial squamous cell carcinomas, lymph nodes metastasis,
      treated with neoadjuvant chemotherapy, checking the p53 "status" and the clinical
      response to the chemotherapeutic treatment (three 5-FU/CDDP cycles). RESULTS: The
      authors found p53 mutations in 3/15 cases. In these cases, at post-chemo
      restaging, it resulted 2 progressions and 1 stability of disease. In the 12 cases
      with wildtype p53: 4 objective improvements and partial responses (PR),
      respectively, of 55% (1), 60% (1), 65% (1), 70% (1), 75% (2) and 90% (2). The 15
      patients were treated then by surgery and adjuvant chemotherapy (three C-F
      cycles). These results seem to confirm the outcome of the researches "in vitro"
      and they provide first correlations between p53 mutations and chemoresistance in
      oral squamous cell carcinomas. The survival evaluation also, in the examined
      cases, shows, but with medium-term follow-up, the tendency to a poor prognosis
      when p53 is altered. CONCLUSIONS: This research outlines the possibility, also
      for oral and maxillofacial tumors, to utilize, p53 as a prognostic and
      chemoresponse marker, useful, with the otherwise well-known prognostic factors,
      for the evaluation of advanced cancers, in the interests of a more suitable
      therapeutic protocol.

PMID- 9578642
TI  - [The distribution of intermediate filaments, histiocytic antigens and neural
      crest-related antigens in the adult dental pulp. An immunocytochemical approach].
AB  - MATERIALS AND METHODS: Ten human healthy teeth were extracted for orthodontic or
      surgical purposes and processed for histological and immunocytochemical
      examination with the streptavidin-biotin-peroxidase method. Highly purified
      antibodies were used to reveal the distribution of intermediate filaments
      (vimentin, desmin, alpha-smooth muscle actin), histiocytic antigens (alpha-1
      antitrypsin, lysozyme), neural and neural-crest-associated antigens (neuron
      specific enolase, chromogranin-A, S-100, synaptophysin, glial fibrillary acidic
      protein, neurofilaments) in the adult pulp tissue. RESULTS: Vimentin
      immunostaining was strongly positive in the network of pulpal fibroblasts. Desmin
      and alpha-smooth muscle actin were present only in the vessel walls. Staining for
      alpha-1-antitrypsin and lysozyme reveals a number of macrophage-like cells in the
      central portion of the pulp. Macrophages were the most dominating immunocompetent
      cells. Negative immunostaining for chromogranin-A demonstrated the absence of
      neuroendocrine antigens in the adult dental pulp. Immunostaining for neuron
      specific enolase, S-100 protein, synaptophysin, glial fibrillary acidic protein
      and neurofilaments were positive, with different intensity, in nerve fibres, but
      no pulp cell was found to be immunoreactive. CONCLUSIONS: The conclusion is drawn
      that the lack of labelling of pulp cells by the neural associated antibodies
      could be due to differentiation processes during tissue development.

PMID- 9578643
TI  - [An in-vivo bacteriological study on the effects of acid etching at the bottom of
      cavities].
AB  - BACKGROUND AND AIMS: The authors evaluate the effect of etching on the presence
      of bacterial colonies at the bottom of sockets. METHODS: For this purpose, 19
      molars with first class carious lesions were selected belonging to patients age
      between 20 and 26 years old, referred for treatment at the outpatient clinics of
      the Dentistry Clinic. The teeth were due to undergo repair with amalgam using, as
      a foundation, fourth generation dentinal enamel adhesives. The clinical trial,
      which was performed in strict conditions of asepsis, included the preparation of
      Black's first class sockets at the bottom of which the author's looked for the
      mark of the "cri dentinaire". Samples were collected of dentin presenting these
      characteristics before and after etching treatment. The latter consisted in the
      application of 37% orthophosphoric acid to dentin for 10 seconds; this served to
      remove the smear layer. The samples obtained in this way were sent to the
      Institute of Microbiology and Virology to undergo culture tests. RESULTS: The
      results obtained show that before etching 75% of the sample was positive for the
      presence of bacteria; this percentage fell to 53% of the sample after treatment.
      CONCLUSIONS: The authors conclude that prepared sockets, even if ready for
      restoration, are in the majority of cases still septic and that the total etch
      technique is not capable of fully removing any bacteria present. Given that the
      effects of acid mordanting on dental tissues are well known, the authors
      recommended paying particular attention to dentinal disinfection before using an
      adhesive system that involves the removal of the smear layer.

PMID- 9578644
TI  - [Oral lesions in systemic lupus erythematosus. I. The etiopathogenic aspects of
      lupus erythematosus].
AB  - The authors investigate lupus erythematosus systemicus, characterized by the
      multiform etiology and autoimmune pathogenesis. Cutaneous lesions, large
      confluent areas of erythema, poikilodermatous lesions, atrophy and necrotizing
      vasculitis (leukocytoclastic vasculitis) occur in patients with lupus
      erythematosus (SLE). Ulcerative lesions are an ACR (American College of
      Rheumatology), (formerly ARA), criterion for the diagnosis of SLE. These lesions
      are suspected of being caused by a mechanism involving circulating immune
      complexes and neutrophils. This observation further supports previous evidence
      that all oral lesions in SLE result from vacuolar degeneration of basal
      keratinocytes. Immunopathologic study of lupus erythematosus shows the
      correlation between HLA-dr positive keratinocytes or Langerhans cells and
      epidermotropic T cells and the immunobiological significance of the antigen
      antibody system in LES.

PMID- 9578645
TI  - [Oral lesions in systemic lupus erythematosus. II. The clinical and therapeutic
      aspects of lupus erythematosus].
AB  - The authors describe the most common clinical characteristics and main parameters
      of SLE. They describe the currently most therapeutic protocol with particular
      reference to circulating immune complex study on patients with SLE, and they
      examine different prospects of applicability and of prognostic result. The aim of
      this paper is to provide an outline of the clinical diagnosis and the
      immunobiological significance of the nucleoprotein autoantibodies and of the
      Ro/SSA antigen-antibody system and the relationship between circulating anti
      Ro/SSa antibody levels and skin disease activity in SLE.

PMID- 9578646
TI  - [Fibrous dysplasia. The clinico-therapeutic picture and new data on its etiology.
      A review of the literature].
AB  - In this paper the authors examine current findings on the etiology of fibrous
      dysplasia. Particular emphasized is the role of the biochemical pathways and the
      genetic mutations occurring in the disease. In fact it is demonstrated that the
      McCune-Albright syndrome, a variant of fibrous dysplasia, is caused by the
      mutations of the GNAS 1 gene that codify for the alfa-subunit of the stimulatory
      guanine-nucleotide binding protein (G-protein). This mutation activates adenylate
      cyclase and consequently increases intracellular concentrations of cAMP. The
      increased signaling through the cAMP is believed to be responsible for the
      clinical characteristic of the McCune-Albright syndrome. The cap is translocated
      to the nucleus where a family of transcription factors is phosphorylated. This
      group of factors regulates the expression of CAp responsive genes: one of them,
      the c-fos proto-oncogene, produces a nuclear protein that binds with other
      proteins encoded by c-jun proto-oncogene, to form a transcription factor, AP-1.
      Several studies have shown an increase of c-fos mRNA in the bone lesions of
      patients with fibrous dysplasia. It suggests that the overexpression of c-fos may
      represent the first step in the carcinogenesis of bone sarcomas. Finally,
      attention is focused on the intravenous use of pamidronate as medical management
      in the treatment of the lesions that are not susceptible to surgical treatment.

PMID- 9578647
TI  - [Odontogenic tumors. The importance of a correct histopathological diagnosis].
AB  - The troubles in the exact diagnosis of odontogenic tumors spring from the poor
      knowledge of the histological type of the lesion, from mutations in the
      ectodermal cells of the tumors and from the uncommonness of the pathology. Wrong
      diagnosis in this field of stomatology often lead to unnecessary surgical
      resection and could be avoid with better cooperation between surgeon and
      pathologist.

PMID- 9578648
TI  - [Aspergillus-induced maxillary sinusitis].
AB  - Maxillary aspergillosis sinusitis more often occur in immunocompromised patients,
      but this pathology is increasing also in healthy people. Many risk factors are
      known and clinical and radiologic findings are aspecific; diagnosis therefore is
      possible with histologic and microbiologic aid. This particular disease and its
      surgical-pharmacological approach is explained.

PMID- 9578649
TI  - [The evaluation of the clinical efficacy and tolerance of azithromycin in
      odontostomatological infections].
AB  - BACKGROUND: Common oral bacteria are involved in the etiology of
      odontostomatological infections and there is a prevalence of Gram negative
      anaerobic microorganisms that are increasingly often found to be resistant to
      common beta-lactamases. In the light of this phenomenon, the use of beta
      lactamases has been replaced by macrolides. The development of azithromycin,
      which is active against anaerobes and characterised by a wider spectrum of action
      against Gram negative bacteria, has opened new horizons in the therapeutic
      approach to odontostomatological infections. AIMS: The aim of the study was to
      evaluate the clinical efficacy and the tolerability of azithromycin in
      odontostomatological infections. The study was performed using an open test
      method, without a comparative drug. METHODS: One hundred patients, including 51
      males and 49 females aged between 18 and 64 years old, were included in the
      study. These patients showed clinical and radiographic symptoms of acute apical
      periodontitis, periodontal abscess, or third molar dysodontiasis. They were
      divided into three groups. The drug protocol used was 500 mg/day for three days.
      The efficacy of the antibiotic was assessed one week after the start of treatment
      by evaluating the evolution of the pathology on the basis of subjective symptoms
      (pain) and objective signs (reddening, swelling, basal temperature). A
      progressive system was used to quantify the clinical findings using an arbitrary
      score from 0 to 3. The tolerability of treatment was evaluated by recording any
      signs observed in the patients' data records. RESULTS: The initial mean score for
      painful symptoms passed from 2.88 to 0.34. The initial mean score for the
      reddening parameter also fell from 2.3 to 0.34. The same results were found for
      the reddening sign which presented a mean value of 2.1 at the start of treatment
      and 0.38 at the end. The 8 patients who presented fever also showed a remission.
      The overall incidence of side effects was 8%. The side effects affected the
      gastrointestinal tract. CONCLUSIONS: From an analysis of these results it can be
      affirmed that azithromycin achieved good therapeutic results in
      odontostomatological infections in terms of both efficacy and tolerability.

PMID- 9578650
TI  - [Emergency and temporary vascular access].
AB  - The vascular access in emergency represents a basic need for every nephrologist
      in order to realize an extracorporeal circuit necessary to perform hemodialysis
      and many other derived therapies. In the eighties a progressive abandonment of
      the external shunt was noted with a concomitant increase of vena cava
      catheterization simpler to perform, especially under echographic control, and
      made increasingly possible by continuous technological improvements. The femoral
      access is utilized in about 30% of cases, especially in critically ill patients,
      due to easy performing procedures and few complications. Subclavian vein is
      abandoned as a first choice in favour of the jugular vein due to frequent and
      severe early complications and to thrombo-stenotic lesions observed in about 50%
      of catheterizations. Prevention and rapid treatment of the complications and
      careful management have an important role in obtaining a prolonged catheter
      survival. Even if, when possible, the classical arterio-venous fistula remains
      the ideal solution, at least in particular patient categories a jugular vein
      utilization as permanent access is justified.

PMID- 9578651
TI  - [Vascular access for chronic hemodialysis: current status and new directions in
      the Piedmont].
AB  - Long survival on dialysis and wide admissions of very old and high risk patients,
      have focused attention to the problem of vascular access in uremic patients. The
      situation is critical in the USA, where PTFE/bovine grafts are utilized in about
      75% of the cases. conversely, AV fistulas are the main type of access in
      Piedmont, where their use approaches 90% of the cases, Cimino-Brescia fistulas
      account for 58% of vascular accesses versus 25% and 9% of proximal AV fistulas
      and PTFE/bovine grafts, respectively. However, the latter progressively increase
      as age and time on dialysis increase. Snuff box fistulas are used only for 3% of
      the cases and this figure is steadily decreasing. In the meanwhile basilic vein
      superficializations, even if limited in numbers (1%), provided in some centres
      satisfactory results in term of survival and function. However, the type of
      access that deserved in the last few years the highest interest is the internal
      jugular vein cannulation (Canaud/Tesio catheter). In a preliminary series of 51
      cannulations in 47 patients, this vascular access was permanent in 28 cases. A
      possible future routine utilization of jugular vein catheters is advisable in
      cases where a waiting period (up to a few months) is requested to allow a new
      fistula to mature or to maintain an empty abdomen in a patient temporarily
      withdrawn from peritoneal dialysis. Due to the heavy engagement for catheter
      maintenance and the high number of removals for systemic (9.8%) or skin exit
      infections (13.7%), a longer stay of indwelling catheters, although actually
      safe, should be limited to selected cases.

PMID- 9578652
TI  - [Complex vascular access].
AB  - Availability of a proper vascular access is a basic condition for a proper
      extracorporeal replacement in end-stage chronic renal failure. However,
      biological factors, management and other problems, may variously condition their
      middle-long term survival. Therefore, personal experience of over 25 years has
      been critically reviewed in order to obtain useful information. In particular
      "hard" situations necessitating complex procedures have been examined but, if
      possible, preserving the peripherical vascular features.

PMID- 9578653
TI  - [Vascular access in hemodialysis. Surveillance and role of percutaneous
      transluminal angioplasty].
AB  - The function of vascular shunts in hemodialysis plays a vital role for the
      efficiency and effectiveness of replacement therapy. A study was performed in 147
      patients undergoing periodical hemodialysis with distal FAV (no = 86), proximal
      FAV (no = 33), PTFE grafts (no = 23), Canaud-Tesio catheters (no = 7). A protocol
      for function evaluation was developed which also included the calculation of
      overall recirculation (R), that was found to be 10.8 + 7% (using the three blood
      sample method). In 28/143 patients the monitoring protocol recommended the use of
      angiography which identified abnormalities in 78% of cases, before the onset of
      thrombotic phenomena. In particular, surgical radiology was able to resolve 94%
      of cases in which angiography revealed a stenosis using percutaneous transluminal
      angioplasty and/or the insertion of one or more stents.

PMID- 9578654
TI  - [20 years' experience with "difficult" vascular access].
AB  - The increased survival of patients in dialysis and the gradual increase in the
      age of uremic patients commencing chronic dialysis raises serious problems for
      the creation and maintenance of efficient vascular access. In cases in which it
      is extremely difficult to create arteriovenous fistulas (AVF) using existing
      upper limb veins, it is possible to resort to vascular grafts, lower limb AVF,
      central venous catheters or refer the patients for peritoneal dialysis if this
      method is technically possible. In order to evaluate the incidence of these
      phenomena in quantitative terms, the authors have made a retrospective analysis
      of patients undergoing vascular access surgery since the opening of the Dialysis
      Centre on 1/9/1973 to 30/9/1996. During this period (277 months) a total of 1,037
      AVF implant operations were performed (in addition to 65 arteriovenous shunts in
      the earlier period and 28 permanent central venous catheters in the last 10
      years). The survival of AVF grafts was lower than that in natural vessels in 384
      patients without clinical risk. In diabetic subjects, those suffering from
      vascular pathologies, systemic diseases, or aged over 70, the survival of AVF was
      distinctly lower compared to the group without these risk factors. However, the
      higher risk group did not show any marked difference in survival between AVF in
      the patient's own veins and grafts. In only 4 out of 1,037 operations it was
      impossible to obtain vascular access in the upper limbs (2 patients were referred
      for peritoneal dialysis and AVF were executed in the thigh in 2 patients). In
      conclusion, the retrospective analysis of this series leads the authors to affirm
      that the rational use of natural vascular accesses normally allows a sufficient
      operating margin; however, in special cases suitable techniques (such as
      permanent central venous catheter or AVF in the thigh) can enable difficult
      situations to be resolved as an alternative to peritoneal dialysis.

PMID- 9578655
TI  - [Vascular access for hemodialysis under difficult conditions. Our experience].
AB  - Having examined the causes that lead, on the one hand, to an increased number of
      vascular accesses in difficult conditions and, on the other, to their reduction
      and having examined their personal series of vascular accesses for hemodialysis
      studied between 4 December 1974 to 30 September 1996, and lastly having outlined
      the correct protocol for the preparation of these accesses, the authors focus on
      vascular accesses created in difficult conditions, namely the exhaustion of the
      natural venous and/or arterial bed below the proximal third of the upper limb. In
      particular, they examine the use of definitive jugular catheters, a more recent
      and therefore non-standardised method, and conclude that, although not regarded
      as vascular accesses of first choice, they should no longer be regarded as heroic
      but, after a short period of learning, they are easy to position and maintain.

PMID- 9578656
TI  - [High-flux arteriovenous fistula at the anatomic snuffbox].
AB  - Based on 25 years of haemodialysis experience, the authors confirm the importance
      of arteriovenous fistula at the anatomic snuff-box by L-L anastomosis with vessel
      end-tie, and assert that, even using small vessels, through simple devices, it is
      possible to achieve high-flux vascular access, that can be employed also for high
      efficiency treatments (HF, HDF). The advantages and the troubles of this vascular
      access are considered and also the reasons that lead to dropping this arterio
      venous fistula too. The authors describe the surgical technique and the devices
      of the procedure, based on their case-reports of 131 arteriovenous fistulas at
      the anatomic snuff-box, immediately working in 95% of the cases and compatible
      with high-flux blood in 67% of cases. Fine adventitial bridle resection is very
      important, because this procedure allows us to rest the venous vessel wall on the
      top of the fistula; the ligature of all collateral vessels is very important too.
      The arteriovenous fistula at the anatomic snuff-box (L-L terminated, with
      anastomotic leak of 5 mm) is the most advisable vascular access for all the
      patients in whom we can plan the start of dialysis some months advance.

PMID- 9578657
TI  - [Transluminal percutaneous angioplasty of stenosis of arteriovenous fistulas; 24
      month follow-up].
AB  - Stenosis is a common cause of the functional loss of vascular shunts used in
      chronic hemodialysis and percutaneous transluminal angioplasty represents the
      elective method to correct these anomalies. A total of 42 percutaneous
      transluminal angioplasties were performed, with a prospective study and follow-up
      lasting an average of 18 months, in 32 patients with insufficient blood flow of
      arteriovenous fistula. In over 90% of cases the procedure restored adequate
      hemodynamic conditions that remained unchanged during follow-up. The authors
      therefore conclude that percutaneous transluminal angioplasty is an efficacious,
      easily performed and low-cost method that does not present major complications.

PMID- 9578658
TI  - [Permanent vascular catheters for extracorporeal dialysis. Preliminary study:
      Canaud and Tesio catheters].
AB  - The use of alternative permanent vascular accesses has recently become
      increasingly common. The possibility of using the catheterization of central
      venous vessels has therefore been taken into consideration, in particular the
      internal jugular vein. During an observation period of 32 months the
      catheterization of the internal jugular vein (IJV) was used as a definitive
      access in 34 patients (12 M, 22 F; mean age 67.5, mean dialytic age 56 months in
      18 patients, in 16 patients the insertion was by primary intention). A total of
      44 IJV catheters were used, of which 18 Tesio and 26 Canaud. The authors examined
      the immediate complications following insertion and the episodes occurring during
      the observation period, including the problem of infection. The insertion of
      catheters was possible in all cases. In terms of catheter function, blood flow
      was adequate for the various purifying techniques. No severe complications were
      reported: gaseous embolism, pneumothorax, hemothorax, hemomediastinum. Infection
      was observed in 11 patients and 13 catheters, of which 70% were mainly provoked
      by Staphylococcus aureus and epidermidis. During the observation period there was
      a drop-out of 14 patients, 11 of whom died (3 following sepsis that failed to
      respond to antibiotic therapy). This preliminary experiment shows that permanent
      jugular catheters may be regarded as a valid access for hemodialytic treatment
      both in patients with severe problems of vascular access and for patients who
      present a short-term prognosis of dialysis and life expectancy at the time of
      starting hemodialysis.

PMID- 9578659
TI  - [Subclavian vein stenosis in hemodialysis patients].
AB  - Six haemodialyzed patient are reported in whom subclavian and brachiocephalic
      vein stenosis secondary to subclavian vein catheterization and to permanent
      cardiac pacemakers led to massive congestive edema of the same arm after an
      arteriovenous fistula/grafts were created. In view of the fact that subclavian
      vein stenosis or occlusion is not associated with any clinical findings and it is
      not possible to identify any predisposing factors associated with the use of the
      catheters, all patients who have had previous subclavian vein catheters or with
      permanent pacemakers should be evaluated to determine the patency of the
      subclavian vein before creation of a permanent access in that arm. Therapeutic
      answers as to haemodialysis access are discussed in these patients with permanent
      pacemakers who need haemodialysis. Because of all of these problems, the practice
      of subclavian cannulation in patients with end-stage renal failure has been
      discontinued in our centre. Good and reliable technology is now available for
      repeated short-term or long-term cannulation of the jugular veins for
      hemodialysis.

PMID- 9578660
TI  - [Quality assurance and control of dialysis access].
AB  - Preliminary experience on total quality program in access surgery for dialysis is
      described; this kind of "border-line" surgery requires peculiar standards,
      documents and quality indexes. The use of a quality index based on a minimum
      success rate of 90% in elective access surgery is proposed. In addition, a "cross
      index", suitable for quality evaluation of different dialysis sectors at the same
      time, is expressed. First interventions aimed at the optimal use of resources are
      described.

PMID- 9578661
TI  - [Comorbidity factors in the dialysis registries and the experience of the
      Piedmontese Registry].
AB  - The parameters used at present by the Dialysis and Transplant Registries of
      various countries to evaluate dialyzed patients' comorbidity show great
      differences, mostly owing to the different epidemiological, social and racial
      characteristics of the studied populations. Moreover, the typology of the
      dialyzed patient is changing: the mean age is increasing, patients with high-risk
      conditions as vasculopathy and diabetes are widely accepted to the treatment.
      Thus the Piedmont Registry will be implemented as follows: new fields about
      comorbidity for clinical (blindness, cachexy and dementia), social (smoking,
      alcohol and drugs addiction) and diagnostic (type of diabetes, of neoplasm, of
      cardiovascular problem) parameters, and questions needing dichotomic response
      (vasculopathy yes or no) will be added. The exact time of appearance of any risk
      factor will be requested, and a field for "others" risk factors will be added as
      well, trying to deeply identify the dialytic population not affected by any
      comorbidity factor. Finally, a new improved control system of the collected data
      will be used: our registry needs to be implemented in the future by such
      evaluations, to go on giving useful informations about epidemiology of the
      dialyzed patients.

PMID- 9578662
TI  - [Analysis of cause of death in the 1st and last periods of the Piedmontese
      Dialysis and Transplantation Registry].
AB  - The aim of this study is to assess the mortality causes in dialysis in the
      Piedmont Region, using the data of the Dialysis and Transplantation Register
      (DTR). Data of a 15-year use of the DTR regarding 5519 hospital dialysis
      admissions were considered. Mortality seems to be particularly due to cardiac
      causes analyzing, also the incidence of other causes of death such as: cachexia,
      sudden death and infection causes.

PMID- 9578663
TI  - [Drugs used in the treatment of arterial hypertension in dialysis patients in the
      Piedmont. What correlations between personal and clinical data can be made from
      the registry data?].
AB  - The therapeutical approach to arterial hypertension in the general population is
      now relatively well classified, whereas it remains a controversial problem in
      dialytic patients. The aim of this study was to evaluate the antihypertensive
      drugs used in dialytic patients in Piedmont and to identify correlations with
      other personal and clinical data. The authors analysed the data in the Piedmont
      Dialysis and Transplant Register concerning new patients admitted to dialysis
      during the period 1990-1995 (2,664 patients at 31/12/1995) and 1,373 patients who
      began dialysis during the period 1990-1993. A study of the antihypertensive drugs
      using in single and combined therapy over the five-year period shows major
      variations in the 45-65 year-old age bracket (increased ACE-inhibitors in single
      therapy, 15.5-25.6%, increased vasodilators in combined therapy, 15.3-21%). In
      patients aged > or = 65 years old a slight increase was found in the use of beta
      blockers in monotherapy. Antihypertensive drugs at the 1st control (1990-1995
      entries) appeared to be stable over the five-year period. From the 1,373 patients
      who started dialysis in the period 1990-1993, with at least three subsequent
      controls, the authors selected those hypertensive or normotensive patients
      receiving ACE-inhibitor therapy (best survival in general population) and
      compared their survival with that of patients receiving alternative
      antihypertensive treatment. No significant differences were found. The stability
      of the antihypertensive drugs taken by these patients over the past 5 years backs
      the hypothesis of a greater attention paid by nephrologists to the introduction
      of new drugs, both because of the frequent onset of collateral effects and owing
      to the special pharmacokinetics present in dialytic patients.

PMID- 9578664
TI  - [Critical review of renal transplantation data from the Piedmontese Regional
      Dialysis and Transplantation Registry].
AB  - On 31/12/1995 a total of 1,128 Piedmontese uremic patients had undergone kidney
      transplantation, with 65% of operations performed by the Regional Reference
      Centre and 35% by extra-regional centres. Waiting time for dialysis was less than
      5 years in over half of the patients most of whom were aged between 40 and 60
      years old. In overall terms, the patient survival rate was 94%, 87%, 75% at 24,
      60, 120 months respectively, with a statistically significant improvement when
      the curve was evaluated in the patient-pool treated with cyclosporine (84% versus
      87% at 7 years). Organ survival was 76% at 21 years and 42% at 10 years, and
      results were again improved by the use of cyclosporine. Pathologies affecting the
      transplanted organ represent the main cause of morbidity; drop-out during
      dialysis is caused above all by immunological diseases. Infectious pathologies
      were responsible for the majority of deaths in this population.

PMID- 9578665
TI  - [Maintenance of the tunnel and skin exit site of peritoneal catheters. Current
      situation and orientation of the dialysis centers of the Piedmont and the Valle
      d'Aosta].
AB  - A questionnaire was sent to the 23 Dialysis Centers of the Piedmont and Aosta
      Valley Regions to probe present trend on the choice of peritoneal catheter, its
      setting, the tunnel conformation, the first use and its maintenance. The
      nephrologists attach great importance to a well fixed subcutaneous tract of the
      catheter: this goal is obtained with wide use of pre-molded catheters, often with
      long and curvilinear tunnel. Avoiding an early use of the catheter and the choice
      of small volumes in the first weeks will permit an efficient stability of the
      cuff and the reduction of the risk of leakage. The choice in maintenance and
      monitoring of the exit-site are various and it often has a protection covering;
      clinical controls are made on a monthly basis.

PMID- 9578666
TI  - [Peritoneal dialysis and chronic dobutamine, two experiences contrasted. Possible
      role and indications in refractory cardiac decompensation].
AB  - The number of patients who develop heart failure (HF) is increasing and is
      expected to increase further in the next decade. Despite the availability of an
      ever-widening array of pharmacological therapy, patients with end-stage HF have a
      poor long-term prognosis. Little attention has been paid to alternative non
      conventional therapy for these patients. The aim of this non-randomized study was
      to describe two non-conventional approaches in patients with HF, refractory to
      conventional medical therapy. The feasibility and long-term efficacy of a
      continuous ambulatory peritoneal dialysis (CPAD: 20 patients) or dobutamine
      intermittent infusions (DOB: 11 patients) was analysed: the mean dobutamin dose
      was 5 gamma/kg/min, and the interval period treatment ranged from 12 hours/day to
      12 hours/week. RESULTS: Both treatments were feasible and non major procedure
      complications occurred. The 6 and 12 month survival rates were 55% (14/20
      patients), 35% (9/20 patients) and 36% (6/11 patients), 18% (3/11 patients) in
      the CAPD patients and DOB patients, respectively. All patients survived at one
      year (38% = 12/31 patients) documented a significant functional improvement and
      quality of life. The conclusions is drawn that the use of CAPD and DOB should be
      considered in those with refractory HF, in whom medical therapy has failed and in
      whom home training is considered feasible. Further studies are necessary to
      define those patients who will benefit from one of these strategies and to
      confirm these preliminary data.

PMID- 9578668
TI  - [Cachexia during dialysis].
AB  - In the Italian language, the term cachexia is a rather picturesque synonym of
      "marasma senile", "senile marasmus", an old definition involving not only old
      age, but specifically senility, the end of the ageing process and marasmus, a
      stagnant and hopeless situation in which all superior organised functions have
      disappeared. The problem of cachexia during dialysis is complex and several
      discordant opinions exist at this regard, partly accounted by different
      definitions of this sluggish entity (or non entity). Actually, the basic question
      is very simple: is cachexia the cause or the effect of failure of dialysis
      treatment? The aim of this study was an evaluation of epidemiological data from
      the Dialysis and Transplantation Registry of Piedmont, a northern Italian Region
      with about 4,350,000 inhabitants, 22 public dialysis Centers, open acceptance to
      dialysis since the mid seventies, a multiple choice dialysis system developed in
      the eighties. In the period 1981-1995, 764 patients died in conditions of
      cachexia. This figure is 20.9% of all deaths recorded, 27.4% over age 65 and
      34.7% over age 75. Despite a likewise significant increase in age and presence of
      comorbid factors, an improvement of patients survival, that reach statistical
      significance in the old age group (> or = 65 yrs), was observed.

PMID- 9578667
TI  - [Immune response to influenza vaccination among peritoneal dialysis patients].
AB  - The influenza vaccination is considered useful in preventing influenza and its
      complications, but its efficacy is variable especially in uremia. The humoral
      efficacy in a group of 15 patients in peritoneal dialysis treatment has been
      evaluated. Antibody responses were measured before vaccination and at time
      intervals of 1-4 months after vaccination. A good response to viruses A
      (A/H3N2/Johannesburg 33/94, A/H1N1/Singapore 6/86), respectively 80% and 66.7%
      and an attenuated response (20%) to virus B (B/Beijing 184/93) was observed. For
      viruses A, the "non responders" were elder patients with a low count of
      lymphocytes. For virus B it is suggested that the low response is perhaps related
      to variable effectiveness of vaccine.

PMID- 9578669
TI  - [DRG/ROD: limits to their application in nephrology].
AB  - The ministerial decrees of 15/4/94 and 14/12/94 defined the new payment schedules
      for hospital services during ordinary and day hospitalization; the hospital
      discharge form (SDO) is the main source of this information. The services are
      defined by the classification of ROD ("raggruppamenti omogenei di diagnosi"),
      adapted from the American DRG ("Diagnosis related groups"), which have
      substituted the traditional system of payment by production factor. On the basis
      of the DRG identified and the length of hospital stay, the Region pays the
      hospital the cost of hospitalization. The main diagnosis at discharge, secondary
      diagnosis, complications and diagnostic/therapeutic procedures all contribute to
      the determination of 489 DRG. Groups of pathologies are reclassified into 25 MDC
      ("Major Diagnostic Categories"). The 11th MDC includes the uronephrological DRG
      (302-333). The nephrological sector has been penalized by the inadequate value
      given to related procedures and diagnostic limitations. In order to guarantee
      efficacious diagnostic and therapeutic procedures, without impoverishing the
      nephrological budget and reducing the management autonomy of the divisions and
      autonomous services with hospitalization, it is necessary to introduce quality
      controls and corrective measures to the procedures that maintain the value of
      diagnosis and comply with financial considerations.

PMID- 9578670
TI  - [Magnesium hydroxide in idiopathic calcium nephrolithiasis].
AB  - BACKGROUND: While in vitro the protective effect of magnesium on calcium oxalate
      crystallization is well known, its clinical relevance in calcium nephrolithiasis
      is still debated. Therefore, the clinical and metabolic effects of magnesium
      hydroxide therapy were evaluated in calcium stone formers. METHODS: Nine patients
      (7 M, 2 F), selected for a low urinary magnesium excretion (uMg 56 +/- 12
      mg/day), were given Mg hydroxide (500 mg/day), with clinical and metabolic
      controls at 3, 12 and 18 months. RESULTS: Urinary Mg/uCreat increased throughout
      the study; uOx/uCreat decreased significantly; uCa/uCreat increased but not
      significantly. The stone recurrence rate decreased from 0.75 to 0.11
      stones/year/patient, throughout the study period. The decrease of uOx is
      considered a more important risk factor in calcium stone patients than a similar
      uCa change; it may be due to a reduced intestinal Ox absorption, for the
      formation of insoluble and not absorbed Mg oxalate. CONCLUSION: In conclusion, Mg
      hydroxide therapy was encouraging in patients with calcium nephrolithiasis and
      low uMg; nevertheless a longer period of treatment is needed to confirm these
      data.

PMID- 9578671
TI  - [Estimation of total body water from routine urea kinetics].
AB  - The comparison of total body water obtained by Watson formula with results of
      bioelectrical impedance (BIA) shows a fair approximation (Delta% = 1.0 +/- 8.45).
      However, when compared to other literature formulas the BIA values are higher (8
      divided by 23%), and this discrepancy needs further analysis. Urea kinetics was
      computed using as input data for distribution volume both the Watson
      anthropometrical and the BIA TBW values: the clearance results do not differ
      significantly (Delta% = 0.74 +/- 8.35). The Kt/V index results are nearly
      identical (Delta% = 0.12 +/- 1.17), due to a mathematical loop: a wrong input of
      volume induces a comparable error of the clearance result, while their ratio is
      unchanged. For practical routine to monitoring dialysis adequacy the Watson
      anthropometrical formula has proven as a satisfactory simple approach. Periodical
      BIA determination provides useful informations mainly when the anthropometrical
      estimation are doubtful and the comparison of data may increase the kinetic
      reliability.

PMID- 9578673
TI  - [Electrophysiological study of 921 cases of carpal tunnel syndrome: its
      application for prognosis and treatment].
AB  - A neurophysiological study of 921 hands with clinical manifestations of carpal
      tunnel syndrome (CTS), 88 of normal individuals and 588 of patients with
      disorders not related with median neuropathy was carried out to establish the
      diagnostic sensibility 130 non-operated on patients with slight CTS were
      controlled one year later. The same was achieved with 105 surgically treated
      patients in order to establish the electrophysiological changes related to
      therapeutic methods. Antidromic sensory conduction and segmentary motor
      conduction of the median nerve were studied along with the difference between
      median and ulnar sensory latencies. Only 84 of the 921 hands (5.2%) showed normal
      electrophysiological findings and 469 (50.9%) minimal changes. 343 hands (37.2%)
      showed signs suggestive of axonal degeneration in sensory fibers and 147 (16%) in
      motor ones. Of the 130 slight CTS not surgically treated, clinical manifestations
      persisted for one year in 118, 17 of which have normal electrophysiological
      parameters. Twenty six (20%) of these 130 hands got worse. Of the 105 CTS
      surgically treated hands, 58 continued with symptoms one year later in spite of
      the electrophysiological improvement in 88.6% of them. Among 588 patients hands
      without CTS symptoms, only 0.8% had electrophysiological signs suggesting CTS. A
      high yield of the electrophysiological diagnosis of the CTS is shown. Symptoms
      frequently persist in patients without definite nerve compression.

PMID- 9578672
TI  - [Usefulness of SPECT in the study of Alzheimer's disease].
AB  - Single-photon emission photometry (SPECT) images of the brains of 60 patients
      with Alzheimer's disease (AD) were compared with the brain scans of 16 healthy
      controls of the same sex and similar ages. SPECT was repeated one year later in
      16 of the AD patients. Perfusion indices for frontal, parietal, temporal and
      occipital regions of patients and controls were compared (Student's tests). Flow
      alterations were located and symmetry examined. The correlation between perfusion
      index for each cortical area and MMSE score was assessed (Pearson's r). Perfusion
      alterations were present in all except one AD patient, and in 65% of AD patients
      such alterations were in the parietotemporal cortex. Severity of cognitive
      impairment in AD patients was related to perfusion changes in the left posterior
      temporal region. Forty-four AD patients showed asymmetrical distribution of
      tracer and in 73% perfusion changes were predominantly in the left hemisphere.
      Altered brain blood flow is common in AD and onset is early. The parietotemporal
      location of defective perfusion is of great diagnostic value. Asymmetry is common
      and the left hemisphere is most often affected.

PMID- 9578674
TI  - [Tolcapone: a different, effective approach to improving dopaminergic treatment
      in Parkinson's disease].
AB  - Tolcapone is a potent, selective, reversible inhibitor of COMT. Coadministration
      of tolcapone with levodopa and a decarboxylase inhibitor prolongs the elimination
      half-life of levodopa and reduces the formation of 3-0-metildopa in a dose
      dependent form. The improvement in the pharmacokinetics of levodopa prolongs the
      motor effects of levodopa. Clinical studies have shown that the concomitant
      administration of levodopa and tolcapone is effective on the management of the
      wearing-off phenomenon. Tolcapone can significantly reduce the off time and
      increases the total on time while simultaneously reducing levodopa dosage and
      frequency. Most adverse events are dopaminergic in nature and related to the
      increase in levodopa bioavailability. Dyskinesias may increase in frequency and
      severity in patients already having dyskinesias and these may appear for the
      first time after adding tolcapone in patients at risk. Diarrhoea is the main
      nondopaminergic adverse event leading to the stop of the drug in less than 10% of
      cases. Taking into account that tolcapone significantly enhance the action of
      levodopa, it would be wise to reduce the total daily dose of levodopa at the same
      time that tolcapone is introduced. No tolerance effect was observed in 12-month
      studies. Tolcapone can be used with standard or sustained release levodopa, and,
      when appropriate, in conjunction with dopamine agonists or selegiline.

PMID- 9578675
TI  - Stiff-man syndrome: an overview.
AB  - Fluctuating stiffness and paroxysmal spasms of the trunk and legs are the primary
      features of stiff-man syndrome and it's variants, progressive encephalomyelopathy
      with rigidity and myoclonus (PERM) and stiff-leg syndrome. The spasms
      characterized by hyperextension of the back and legs are both spontaneous as well
      as stimulus-sensitive. They can be excruciatingly painful and are frequently
      accompanied by symptoms of autonomic dysregulation. Hyperreflexia may be the only
      pathological finding on the neurological examination. Most patients show
      psychiatric disturbances suggestive of psychogenic movement disorder and this may
      cause delays in adequate pharmacotherapy. The disease progresses over the span of
      months to years rendering many patients wheelchair-bound or bedridden. GABA
      mimetics are most effective in treating symptoms, but tolerance and life
      threatening withdrawal symptoms are common drawbacks. For therapy-refractory
      patients, intrathecal baclofen represents a good alternative. The diagnosis is
      based on clinical, biochemical and electrophysiological findings. Spasmodic
      reflex myoclonus is observed in nearly all SMS patients. It consists of well
      reproduced reflex EMG-activity commencing 50-80 ms after medial or tibial nerve
      stimulation and lasting several seconds thereafter. The activity is first
      myoclonic then spasmodic in nature, and commonly begins in the muscles most
      severely affected before spreading bidirectionally along the neuraxis. Spasmodic
      reflex myoclonus and the high incidence of antibodies against GAD are suggestive
      of an autoimmune disorder affecting GABAergic neurons in the spinal cord, but the
      precise locus of dysfunction remains to be elucidated.

PMID- 9578676
TI  - [Idiopathic cervical plexopathy].
AB  - We describe a 26 year-old woman with cervical plexopathy with damage of left
      superficial or cutaneous branches, and left cervical sensory dorsal rami. Picture
      began acutely and vanished few days later. We ruled out known etiologies like
      traumatisms, tumours and surgical and anaesthetic complicated procedures,
      therefore the patient suffered an idiopathic cervical plexopathy. We hypothesize
      two possibilities for this clinical picture: an autoimmune reaction or a muscular
      entrapment.

PMID- 9578677
TI  - [Haemophilus influenzae type B meningitis: typical and atypical presentation].
AB  - We present 2 cases of Haemophilus influenzae meningitis. The first is a patient
      with atypical simptomatology: abdominal pain, fever and two days later pain in
      the back of his legs. Abdominal pathology was not found. The cerebrospinal fluid
      (CSF) showed polymorphonuclear cells, hyperproteinorachia and lowered glucose.
      CSF culture revealed Haemophilus influenzae, blood culture was sterile. The
      second had suffered surgery at maxilar and ethmoid sinuses four years before, and
      unknown germ meningitis 6 months before. Haemophilus influenzae was isolated from
      CSF cultures and CSF rhinorrhea was detected by isotopic cisternography.

PMID- 9578678
TI  - [Uncommon neurologic complications related to varicella-zoster virus].
AB  - Neurological complications caused by varicella-zoster virus, excluding post
      herpetic neuralgia and aseptic meningitis, are infrequent and varied. Other
      complications, which have been described are peripheral motor neuropathy, cranial
      nerve palsies, meningoencephalitis, Guillain-Barre syndrome, myelitis, herpes
      zoster ophthalmicus with delayed contralateral hemiparesis and Reye syndrome. We
      present 4 patients with infrequent neurological complications associated with
      varicella-zoster virus: 3 cases of meningoencephalitis and one case of myelitis.

PMID- 9578679
TI  - [Acute cerebellar inflammation due to rubeola virus].

PMID- 9578680
TI  - [Aseptic meningitis due to OKT3].

PMID- 9578681
TI  - [Evaluation of the quality of life in artificial nutrition].
AB  - If we define quality of life as being the social, physiological, mental
      intellectual, and general well being of people, we realize that there is no known
      health care system that is able to guarantee that well being in all its possible
      aspects. When we as clinicians assess the positive effects of a treatment applied
      to a patient, we are not only assessing the offered quality of life, but also the
      quantity of life, so what we are really assessing is the usefulness. We could
      say, therefore, that while the quality of life is subjective, not exact, and
      cannot be quantified, the usefulness on the other hand, can and should be
      measured and quantified, even though, as this is a subjective assessment, it is
      somewhat difficult to quantify. The object of our publication is to find an
      appropriate method for assessing this parameter in the area that concerns us:
      artificial nutrition. Artificial nutrition is indicated when the patient cannot
      does not want to, or does not know how to eat in the natural manner. Therefore,
      in principle it could seem inhuman and even unethical to deny a vital support
      measure that is practically without any risks in a patient who cannot feed him-or
      herself. However, in a situation of limited resources, if the treatment were
      inappropriate we should consider that possibility. Under these circumstances we
      could consider that even a concept as essential as nutrition (in this case
      artificial) would lose its inalienable character. In order to assess usefulness,
      one must include parameters that can be quantified in percentages and whose
      results can be set out in units of time (years, months, or days). We use the
      concept of the individual usefulness, whose unit of time is the QALY (Quality
      Adjusted Life Years). In 1996 we made a personal modification of Rosser's Index,
      which was specific for evaluating the quality of life obtained by means of
      artificial nutrition. This consisted of substituting the assessment parameters of
      intensity of pain, by other that are specific in function of the limitation of
      the ingestion capacity presented by the patient who was subjected to AN. The
      third factor that corresponds to the concept of usefulness would be the index of
      beneficial applicability percentage of patients who benefit from the support. The
      combination of these three factors, applicability, life expectancy, and quality
      of life, would yield the usefulness of the procedure. In order to assess
      usefulness in all its aspects, one must also define intention, as this can be
      applied with three goals: essential or curative, complementary or adjuvant, and
      maintenance or merely palliative. We can say that the economical limitations and
      the cost of the therapeutic resources leads to rationing by the administration.
      In the face of this action, we would recommend a rational and reasonable
      restriction of the available resources, which lead to the so-called
      rationalization, a term that is more correct ethically and esthetically, than
      rationing. As a final conclusion we could state that ethics and economics help us
      to use the resources appropriately, without any contradictions, as the economy
      attempts to give the society the greatest possible degree of well being based on
      the available resources, and that is an ethical objective, The quantification of
      the benefits obtained by applying a treatment using measureable units, involves
      socio-economic concepts such as usefulness, cost/benefit, quality of life, etc.
      should not elicit rejection as though we were dealing with a merchandising of our
      ethical values. We clinicians are capable of assessing this together, both with
      regard to the obtained costs and benefits, and with regard to the final results,
      both intra- and extra-hospital, and using the appropriate tools, we can reach
      conclusions that can guide us objectively in making decisions, with the aim of
      optimizing our therapeutic actions.

PMID- 9578682
TI  - [Administration of glutamine and its dipeptides in parenteral nutrition. Which
      patients are candidates?].
AB  - Despite the fact that glutamine is not considered to be an essential amino acid,
      it is the amino acid found in the greatest concentration both in plasma (26%) as
      in skeletal muscle (75%). These levels may decrease in post-operative, trauma, or
      critical patients. Glutamine performs many functions in which its demand may be
      increased, such as: it is a precursor of the synthesis of nucleotides; it is an
      activator of the protein synthesis and at the same time it inhibits the
      degradation; it is an activator of glycogen synthesis; it is a metabolic
      substrate for rapidly replicating cells; it is an energy source for the
      enterocyte which is so important for maintaining the integrity and the function
      of the intestinal barrier, and the consumption thereof may be increased under
      conditions of stress. The administration of glutamine intravenously leads to two
      physical-chemical problems; the first is its low solubility in water; at 20
      degrees C this is only 36 g/l, and the second problem is its low chemical
      stability in an aqueous solution at 22-24 degrees C, this being 11 days. This
      problem has led the industry to research two dipeptides of glutamine; L-alanyl
      glutamine, and L-glycyl L-glutamine, both of which are much more soluble and much
      more stable. At present there is still a controversy regarding the dosage of
      glutamine and its dipeptides, with the dose being 0.19-0.29 g/kg/day of L
      glutamine or its dipeptide forms, in surgical post-operative periods or to
      prevent bacterial translocation, and in patients who are candidates for bone
      marrow transplants, the administered dose has been 0.37-0.57 g/kg/day. The
      purpose of this study is to review the existing bibliography regarding the
      efficacy of L-glutamine or its dipeptides in four possible indications for its
      application in the daily clinical practice, such as: a) In post-operative
      surgical patients of major or medium surgery, glutamine or its dipeptides reduces
      the losses of muscular glutamine and its catabolism, showing a less negative
      nitrogen balance. b) Whether it avoids bacterial translocation. c) Whether it
      favors the response of the immunological system. d) Whether in patients who are
      candidates for bone marrow transplants this decreases the side effects due to
      chemotherapy and radiotherapy such as mucositis, or whether it decreases the
      number of days of neutrophil recovery. At present, on the European market there
      are two commercially available brands of glutamine dipeptides: Dipeptiven, by
      Fresenius Laboratories, Germany. A 100 ml vial which corresponds to 20 g of L
      alanyl L-glutamine (8.2 g of alanine + 13.46 g of L-glutamine). This is added to
      the standard amino acid solution. Glamin, Pharmacia and Upjohn Laboratory,
      Sweden. This is an amino acid solution with 13.4% essential and non-essential
      amino acids which are equivalent to 22.4 g of nitrogen/l, and which contain 30.27
      g L-glycyl-L-glutamine (10.27 g of glycine + 20 g of L-glutamine).

PMID- 9578683
TI  - [Spanish contribution to the creation of a European analytical database of trans
      fatty acids].
AB  - Within the AAIR Program of the EU titled Evaluation of the Ingestion of Trans
      Fatty Acids (FA) and its association with cardiovascular risk factors in European
      countries (TRANSFAIR), which is being carried out in 16 countries with different
      alimentary habits, among which is our country, we have developed the following
      study. Based on the information derived from the last National Nutrition and
      Feeding Study (ENNA-3), we have made up a list of foods which make up 95% of the
      total ingestion of lipids, and it also includes those which although they are not
      included within this percentage, may have an especially high trans isomer content
      as a result of their processing. The foods selected for the analysis belong to
      different food groups: cereals, milk products, oils and fats, meats, various, and
      pre-cooked foods, until making up a total of 100 foods for each country. The
      central analysis laboratory is that of the Department of Human Nutrition, TNO
      Nutrition and Food Research, Zeist (The Netherlands). In each sample, in addition
      to the total lipids, one determines the saturated and unsaturated fatty acids,
      including the cis and trans isomers. The trans FA's measured were: C14:1 T9,
      C16:1 T9, C18:1 T, C18:2 T, C18:3 T + C20:1 T, C20:2 T11,14, and C22:1 T13. Of
      the samples analyzed, the highest percentages of trans FA with respect to the
      total FA corresponded to the following foods: French fries, pre-cooked and frozen
      croquettes sliced bread, margarine, cakes, and frozen mille feuilles dough of
      different industrial brands. The lowest percentages of trans FA's were found in
      refined vegetable oils (sunflower and olive), those used for deep frying, and
      those discarded in catering, as well as in some commercial brands of cookies and
      ice creams. Pure chocolate, different brands of sweetened powdered cocoa, and
      ready to make chocolate, did not contain and trans FA.

PMID- 9578684
TI  - [Changes in the post-kidney transplantation body composition: different behavior
      between men and women].
AB  - A kidney transplant often leads to an increase in body weight, with an altered
      composition of the organism. This study assessed the body composition of a
      population with kidney transplant and an excess of weight (IMC > 25), using
      anthropometry, electric bio-impedance, and infrared interactance. The results
      were compared with the mean values (P50) for the Spanish population, and the
      differences between men and women were analyzed. The assessment of the body
      composition using anthropometry resulted in weight percentages, -mid-arm
      circumference, and -mid-arm muscle circumference of the upper arms, which were
      slightly higher than the P50, without there being any differences between the two
      sexes. The triceps fold showed values which were much higher than the average
      value, and this was more markedly seen in male. All patients showed an android
      type obesity pattern, and this was greater in men. The electric bio-impedance
      analysis and the infra-red interactance showed high fat levels for both sexes,
      without any statistically significant differences with respect to the percentages
      of fat mass, lean mass and water with both methods. The study has shown that the
      weight increase as a result of the kidney transplant, is mainly accompanied by an
      increase in the adipose tissue, and this is more marked in patients of the male
      sex, in such a way that the typical significant differences between both sexes
      with respect to the fat mass, commonly seen the general population, disappear.

PMID- 9578685
TI  - [Incidence and risk factors of mechanical complications in parenteral nutrition].
AB  - The objective of the present study is to determine the incidence of mechanical
      complications in patients with parenteral nutrition in our hospital, and to study
      which factors associated with catheterization in these patients are related to
      the appearance of different types of mechanical complications. All the central
      venous catheters registered during the time period between 1988-1994 were
      included. For the statistical treatment 5 logistic multiple regression models
      were designed in function of the different types of mechanical complications
      studied (dependent variable) and in relation to the defined risk factors
      (independent variables). The difference was considered to be statistically
      significant when, for each variable, this is not 1 for the confidence interval.
      The understanding of the different risk factors associated with the appearance of
      mechanical complications allows a better level of clinical action in the
      prevention of these types of complications.

PMID- 9578686
TI  - [Morphological changes induced by valproate and its administration concomitant
      with folinic acid or S-adenosylmethionine in pregnant rats].
AB  - Neural tube defects (NTD) are serious congenital abnormalities that have a
      multifactorial etiology, including both genetic and environmental effectors (for
      example, diet and/or drugs). Valproic acid (VPA) is a frequently used anti
      epileptic drug that has a potentially teratogenic character, as well as the
      capacity for inducing NTD and other less serious malformations. However, the
      mechanism of action of VPA has not been clearly established, and it has been
      suggested that it interferes in the folate cycle and therefore, with the
      methionine/methylation, possibly through a metabolic blocking of some biomarker
      that is a key of the cycle, such as for example S-adenosylmethionine (SAM) and
      folic acid (FA). The objective of the present study is to analyze the
      morphological and histological changes, which can occur in a high risk
      experimental model after the administration of VPA as well as for the induction
      of NTD and other malformations. In addition, the protective roles of the
      administration of folic acid, 5-formyltetrahydrofolate (FOL) and S
      adenosylmethionine (SAM) are assessed. For this pregnant "Wistar" rats classified
      according to the following treatments: 1) VPA (300 mg/kg/day on days 8, 9, and 10
      of the pregnancy); II) VPA (300 mg/kg/day on days 8, 9, and 10 of the pregnancy)
      and FOL (4 mg/kg/day i.p. on days 8, 9, and 10 of the pregnancy); III) VPA (300
      mg/kg/day on days 8, 9, and 10 of the pregnancy) + SAM (10 mg/kg/day, on days 1
      10 of the pregnancy); IV) CONTROL (no treatment). VPA decreases the fertility
      index by 25% compared to the control group, it increases the number of
      reabsorptions by mother (1.3 +/- 0.5 vs 1.0 +/- 0.5), and decreases the number of
      fetuses compared to the control (9.0 +/- 1.4 vs. 12.6 +/- 0.9). In the VPA + FOL
      group, the numbers for these parameters approach those of the control group and
      the VPA + SAM group is no different from the VPA group, showing no protective
      factors. With respect to the bone alterations observed, when these are grouped
      according to whether they affect the skull, trunk, and extremities, it is seen
      that there are no significant differences between the groups. The histological
      study and the immunohistochemical analysis show liver alterations in all groups
      treated, and a lower number of lymphocytes in the VPA group, and a greater number
      of Kupffer cells, The results are discussed in relation to, first, the effect of
      VPA per se in the interference of the methionine/methylation cycle, and secondly,
      with regard to how folic acid and/or S-adenosylmethionine can improve or not some
      of the harmful effects induced by VPA.

PMID- 9578688
TI  - [Bilirubin and parenteral nutrition (TPN) in the newborn: too many loose ends to
      be tied up].

PMID- 9578687
TI  - [Percutaneous endoscopic gastrostomy and gastrojejunostomy. Experience and its
      role in domiciliary enteral nutrition].
AB  - Percutaneous Endoscopic Gastrostomy (PEG) and its variation Percutaneous
      Endoscopic Gastrojejunostomy (PEGJ), has become the method of choice to achieve
      an enteral access route in patients who require long term enteral nutrition,
      especially in the area of the At Home Enteral Nutrition (AHEN). We present our
      experience on the first PEG's and PEGJ's carried out in our hospital. MATERIAL:
      We studied 48 patients (14 women and 34 men) in whom a PEG/Percutaneous
      Endoscopic Gastrojejunostomy (PEGJ) was indicated, as they required enteral
      nutrition for prolonged periods of time (> 4 weeks) and/or they presented
      obstructive dysphagia, neuromotor dysphagia, or incorrigible vomiting in the two
      cases in whom PEGJ was carried out. 34 patients underwent the Ponsky-Gauderer
      technique, 6 patients underwent the Sacks-Vine technique, and 2 patients
      underwent a PEGJ. 24 hours after the PEGJ enteral nutrition (EN) was begun in a
      progressive manner. During the hospitalization period there was a daily follow up
      of the patient. In those cases in which At Home Enteral Nutrition was programmed,
      the patients/families were trained in the techniques and the care of the PEG and
      the EN, and the control was carried out through the Nutrition out patient
      department. RESULTS: PEG was successfully carried out in 42 patients (88%). 35
      patients had previously been given EN through a naso-gastric tube (NGT), while in
      7 cases the PEG was the first enteral access route. The average duration of the
      PEG was 212 days, and 27 patients (64%) needed the PEG for more than 3 months.
      The mean caloric supply was 1921 +/- 200 kcal/day. The mode of administration was
      by means of an intermittent infusion by gravity in 31 cases, and by continuous
      infusion using a volumetric pump in 11 patients. Two patients with pregnancy
      induced hyperemesis underwent a PEGJ in the 3rd and the 4th month of pregnancy,
      with the pregnancy being successfully brought to term and ending in vaginal
      deliveries. Carrying out a PEG permitted release from hospital and the
      programming of At Home Enteral Nutrition in 30 patients. With respect to the
      evolution of the patients, 22 patients have died during the course of the study.
      18 patients remain in follow up in an ambulatory Enteral Nutrition program, and
      in the two patients with pregnancy induced hyperemesis, the PEGJ was removed
      after the pregnancy was successfully ended. There were no complications of any
      kind in 21 patients. The most common complication was the infection of the
      gastrostomy, which occurred in 13 patients. There was an accidental removal of
      the gastrostomy tube in 3 patients. In 3 cases there was an eversion of the
      gastric mucosa through the ostomy within the first 24-hours, and 20 days after
      the PEG respectively. In 2 cases there was an incarceration of the gastrostomy
      tube in the abdominal wall. Only two patients showed an important reflux of the
      gastric contents. There were no deaths as a result of PEG complications.
      CONCLUSION: From our experience we can conclude the advantages of PEG as a long
      term nutritional support, showing a low incidence of complications, and the
      endoscopic technique has a zero mortality.

PMID- 9578689
TI  - [Rise in intraocular tension in microkeratome sections (LASIK) and with the GTS
      trephine system for keratoplasty].
AB  - Microkeratome systems are being increasingly applied in lamellar corneal surgery
      (e.g., LASIK). The results of the few studies on intraocular pressure changes
      during the microkeratome cut vary widely. In this study, we examined the
      intraocular pressure pattern (IOP) in relation to the initial pressure. METHODS:
      We performed lamellar corneal cuts on freshly enucleated porcine bulbs with three
      different microkeratome systems and different setting for the initial pressure
      (10, 20 and 30 mm Hg). The bulbs were cannulated, and the IOPs were recorded
      online with a two-chamber measuring system. In addition, we examined the GTS
      trephine system applied for corneal transplantation. RESULTS: It became obvious
      that there were significant differences between systems (significance level, P =
      0.05). With an initial pressure of 10 mm Hg the measured values of the Schwind
      system are significantly lower than with the Polytech system, and these values
      are again significantly lower than with the Chiron microkeratome. With 20 mm Hg
      the Chiron system shows significantly higher values than both other systems. With
      30 mm Hg initial pressure, the pressure values with the Schwind system and with
      the Chiron microkeratome are significantly higher than with the Polytech system.
      Thus with all microkeratome systems the middle and maximum pressure values rise
      in correlation with the initial pressure levels. This effect was not seen with
      the trephine system. With the same initial pressure, the standard deviation of
      the measured data of different mikrokeratomes was low (range 3.1-9.0 mm Hg).
      CONCLUSION: The pressure values shown are higher than the data published by the
      manufacturers. There is current discussion as to whether these pressure values
      are dangerous (e.g. bleeding) or not. The pressure values reached intraocularly
      during the microkeratome cut depend on the system and also on the present initial
      intraocular pressure values. Only with the same initial pressure can reproducible
      applanation and cutting conditions be obtained, which guarantee stable quality of
      the cut.

PMID- 9578690
TI  - [Laser in situ keratomileusis (LASIK) for correction of myopia and astigmatism].
AB  - PATIENTS AND METHODS: In order to better define the potential advantages and
      risks of laser in situ keratomileusis (LASIK), we designed a prospective study
      including 73 eyes. RESULTS: After 6 months, 62 eyes were examined. Myopia was
      corrected from -6.10 +/- 3.12 (mean +/- standard deviation) to +0.04 +/- 0.66 D,
      with 54 eyes (87.1%) being within +/- 1.00 D of emmetropia. Astigmatism was
      corrected from -1.07 +/- 1.02 to -0.32 +/- 0.89 D. Uncorrected visual acuity was
      0.5 or better in 59 eyes (95.2%) and 1.0 or better in 27 eyes (43.5%) 6 months
      postoperatively. More than one line in best-corrected visual acuity was lost by 6
      eyes (9.7%), with most of these eyes being highly myopic. There was no change or
      a gain in lines in best corrected visual acuity in 42 eyes (66.1%).
      Intraoperative complications arose in two eyes (2.7%); in one eye, visual acuity
      was temporarily decreased. More treatments were performed in 7 eyes (9.6%).
      Postoperatively, no haze, scars or central islands were detected. Patient
      satisfaction after LASIK was high: 97.3% were pleased or very pleased with the
      result. CONCLUSIONS: In conclusion, LASIK is effective in the correction of
      myopia and myopic astigmatism. Although complications more frequently occurred in
      the correction of higher refractive errors, LASIK seems to be relatively safe
      compared with other refractive methods.

PMID- 9578691
TI  - [Serum-free cultivation of bovine stromal fibroblasts].
AB  - The purpose of the present study was to conduct a comparative evaluation of the
      effect of several serum-free culture conditions on adhesion, population doubling,
      cryopreservation and PDGF-induced effects on cell proliferation of bovine stromal
      fibroblasts (BSF). Additionally, these effects were compared to serum-containing
      cultures. METHODS: Only second-passage BSF were used. Cells were cultured using
      four different culture media (WM/F12, WM/F12 + FCS 1%, LR-1, DMEM). After 24 h,
      plating efficiency was determined using a cell-counter system. Subsequently, the
      cells were seeded at a density of 100 cells/mm2 and cultured for 10 days using
      the different culture media. Cell number was determined at day 2, 4, 7 and 10
      after seeding. Furthermore, the effect of 50 ng/ml PDGF-BB on the proliferation
      of BSF was tested for these conditions. Cell vitality was determined after
      cryopreservation of two weeks for each culture medium. RESULTS: The plating
      efficiency of BSF ranged from 50.2 to 55.5% for the serum-free culture media in
      contrast to serum-containing conditions, where plating efficiency was 94.8%. With
      WM/F12 + FCS 1%, a population doubling of 1.27 was observed after an incubation
      period of 10 days. In contrast, cultivation under serum-free conditions caused
      neither significant cell proliferation nor cell loss. The stimulation of cell
      proliferation with PDGF-BB was shown to be 28% (LR1), 40% (WM/F12 + FCS 1%) 76%
      (WM/F12) and 95% (DMEM) compared to the control. While cell vitality after cryo
      preservation was found to be 62.7% using WM/F12 + FCS 1%, vitality using serum
      free media was 12.6-22.8%. CONCLUSIONS: The results of the present study
      demonstrate that with respect to optimal cell adhesion and cell vitality after
      cryo-preservation, serum-containing media should be used. BSF cultured under the
      serum-free conditions used in the present study can be maintained quiescent and
      vital for at least 10 days. Therefore, these serum-free media are useful for cell
      culture studies (e.g., determination of proliferation and cytotoxicity).

PMID- 9578692
TI  - [Post-traumatic endophthalmitis after penetrating eye injuries. Risk factors,
      microbiological diagnosis and functional outcome].
AB  - BACKGROUND: Endophthalmitis associated with penetrating injury represents a
      distinct kind of intraocular infection. The preceding trauma, infective agents
      and inflammatory changes determine the functional outcome. MATERIALS AND METHODS:
      In a retrospective study, 18 patients with endophthalmitis were investigated and
      compared to a control group of 54 patients with penetrating ocular trauma. A
      number of clinical variables were evaluated for association with an increased
      risk of endophthalmitis. RESULTS: Risk factors found to be significant were: (1)
      a purely corneal wound, (2) surgical primary repair more than 24 h after injury
      and (3) initiation of intravenous antibiotic therapy later than 24 h after
      trauma. A two-fold increased relative risk was related to the presence of an
      intraocular foreign body, lens injury and a wound length less than 5 mm. Direct
      inoculation of surgical specimens and immediate microbiological processing
      succeeded in the presumptive identification of infective agents with preliminary
      therapeutic recommendations in 72% of the patients. CONCLUSIONS: In "risk eyes"
      particular attention should be paid to prophylaxis and signs of infection.

PMID- 9578693
TI  - [Prognostic factors in surgery of macular holes].
AB  - Idiopathic macular holes are today treated surgically with good results. The
      prognostic value of factors predictive for the anatomical and functional outcome
      has not been completely evaluated. PATIENTS AND METHODS: One hundred and thirty
      five eyes with penetrating macular holes (stage II-IV) were investigated
      prospectively. The mean follow-up was 19.5 months (6-50 months). RESULTS: In 86%
      of cases the hole was closed postoperatively. The age of the macular hole proved
      to be a significantly predictive factor for the outcome; the age of the patient
      did not. The diameter of the hole showed no influence on the results. Application
      of autologous serum in front of the hole did not significantly improve the
      anatomical, but the functional results. The strongest improvement of visual
      acuity was seen in eyes with poor preoperative function. In 118 eyes a prefoveal
      membrane could be peeled off. Seventeen eyes without detectable membrane showed
      identical results. CONCLUSION: Some predictive factors in macular hole surgery
      are proven, others remain uncertain. Identical results in eyes with and without
      prefoveal membranes support the assumption of different pathomechanisms in
      macular hole formation.

PMID- 9578694
TI  - [Stereotactic conforming irradiation of choroid metastases].
AB  - The aim of our study was to develop noninvasive stereotactic radiotherapy for
      patients with choroidal metastases. METHODS: The head of the patient was
      immobilized by an individual cast mask. The target volume and adjacent critical
      structures were three-dimensionally segmented based on ophthalmological findings
      and MRI. The beam angles were optimized by a beam's eye view technique with a
      micro-multileaf collimator. We use a linear accelerator with 6-MeV photons. A
      patient was treated in a phase I/II trial with a single dose of 22.5 Gy. RESULTS:
      The accuracy of stereotactic positioning of the eye was 0.8 mm. The dose
      gradients were 15% mm. It was possible to spare the lens and the lacrimal gland
      in all cases. The treatment with four to six fields took 35-50 min and was
      tolerated without acute complications. CONCLUSIONS: We introduce a new method to
      treat choroid metastases by stereotactic radiotherapy. This method allows to
      concentrate the dose to the target and to spare adjacent critical structures. One
      of the advantages of this noninvasive treatment is the short treatment time. The
      clinical role of this method has to be evaluated based on long-term results of
      tumor control and visual outcome in these patients.

PMID- 9578695
TI  - [Eye involvement in Chagas disease (American trypanosomiasis). 1996/1997 studies
      in Paraguay].
AB  - BACKGROUND: Last year's pilot study, which examined for the first time a
      representative group of patients with Chagas disease, showed that in this
      parasitosis changes in the ocular fundus can be expected in the form of defects
      of the retinal pigment epithelium. Examination of more patients in this study
      should give further information about the character and extent of the alterations
      found. MATERIALS AND METHODS: After serological confirmation of the disease, we
      performed an ophthalmological examination of the anterior and posterior segments.
      RESULTS: In 21 out of 23 patients the fundus was unobtrusive; 1 patient showed
      fibrae medullares and 1 patient clear pigment dispersion on the posterior pole.
      Together with the pilot study, a total of 102 chagasic patients were examined. In
      8 patients (7.8%) defects of the retinal pigment epithelium were found, which did
      not cause any significant loss of vision. CONCLUSIONS: We presume that the
      described defects are a matter of rare and harmless postinflammatory or
      immunological changes in the American type of trypanosomiasis.

PMID- 9578696
TI  - [Prognosis in orbital gunshot injuries].
AB  - No reviews of orbital gunshot injuries have been published in German
      ophthalmological journals. In this article biomechanical and prognostic factors
      of this rare type of injury are analysed. PATIENTS AND METHODS: We report on 4
      patients, aged 20-63 years, who tried to commit suicide by shooting themselves in
      the right temple. Clinical and radiological diagnosis as well as treatment by an
      interdisciplinary team are reported. RESULTS: All patients became blind on the
      right side despite immediate surgery including reconstruction of the injured
      bones and soft tissues. Three of four patients suffered severe functional defects
      in the left eye; one of them is now blind. CONCLUSION: Orbital gunshot wounds are
      severe injuries. The prognosis depends on the course of the bullet and the
      interdisciplinary care.

PMID- 9578697
TI  - [Cyclophotocoagulation with the diode laser. Study of long-term results].
AB  - To assess the clinical effectiveness of glaucoma therapy with diode laser
      cyclophotocoagulation, 106 eyes (51 eyes with primary open-angle glaucoma, 22
      eyes with secondary glaucoma, 10 eyes with narrow-angle glaucoma, 23 eyes with
      other glaucomas) of 87 patients were treated. Using a diode laser coupled with a
      fiberoptic probe, ending in a focusing tip, all eyes were treated with 24-30
      spots over 360 degrees and 2.8-3.5 J of energy, 1.5 mm posterior to the limbus.
      The intraocular pressure was obtained over a period of time until 8-24 months
      after operation. Additionally, morphological changes of the ciliary body were
      observed in 25 eyes by means of ultrasound biomicroscopy. RESULTS: The IOP
      decreased from a baseline mean of 25.0 +/- 5.7 mm Hg to 17.6 +/- 5.3 mm Hg
      directly after operation and increased slightly to 18.0 +/- 6.0 mm Hg in the
      following 24 months. Successful control of IOP (IOP constantly < 22 mm Hg or pain
      relief in blind eyes) occurred in 90 of 106 eyes (84.9%). In 23 eyes more than
      one treatment was given. In 6 eyes another IOP-reducing operation had to be
      performed. In 19 eyes slightly elongated intraocular inflammatory reactions were
      seen, without any serious complications. The morphological investigations showed
      in 22 of 25 cases temporary edema of the ciliary body. A temporary detachment of
      the ciliary body was seen in 8 eyes. CONCLUSIONS: Diode laser
      cyclophotocoagulation is an effective and safe procedure to reduce IOP in
      different types of glaucoma over a long time. Postoperatively, a temporary
      inflammatory reaction of the ciliary body was observed with no correlation to the
      degree of reduction of the IOP.

PMID- 9578698
TI  - [Late dislocation of a plate haptic silicone lens into the vitreous body after
      Nd:YAG capsulotomy. A case report].
AB  - We describe a case that was referred 10 months after Nd:YAG laser treatment with
      a posteriorly dislocated silicone intraocular lens (IOL) into the vitreous
      cavity. PATIENT: A 70-year old white woman underwent uncomplicated
      phacoemulsification with in-the-bag placement of a Chiron silicone plate haptic
      lens through a 5.5- mm continuous circular capsulorhexis. The patient was fine
      until 9 months postoperatively when she complained of a decrease in visual acuity
      due to capsular fibrosis. A successful Nd:YAG laser capsulotomy was performed,
      resulting in an increase in visual acuity. Ten months later, the patient noted
      acute and atraumatic loss of vision, and the IOL was found to have dislocated
      posteriorly onto the retina. RESULTS: The dislocated IOL was removed via the
      anterior chamber following pars plana vitrectomy. Perfluorocarbon liquid was used
      to elevate the slippery lens from the retinal surface. The IOL was removed by a
      Sato Knife from the anterior chamber, followed by implantation of a one-piece
      PMMA IOL in the ciliary sulcus. CONCLUSION: Silicone plate haptic IOLs seem to
      present special risks for dislocation. Shrinkage of the anterior capsule exerts
      centripetal forces on the ends of the plate haptic, causing the optic to move
      posteriorly and to exert pressure against the posterior capsule. If either the
      posterior or anterior capsule is disrupted by Nd:YAG laser treatment, the forces
      created by capsular contraction against the flexible lens may cause extension of
      radial tears and appear to be a substantial risk for further capsule-tearing,
      releasing the IOL into the vitreous cavity, even months later. The forces of
      capsular contraction can impart a spring-loading effect on plate haptic silicone
      lenses. Due to inadequate capsular adherence, these lenses are at risk of
      posterior dislocation from capsular rents following Nd:YAG laser treatment.

PMID- 9578699
TI  - [Maculopathy in long-term chloroquine therapy].

PMID- 9578700
TI  - [Amblyopia. 6th Meeting of the Bielschowsky Society for Amblyopia Research, 29-31
      August 1997 in Giessen].

PMID- 9578701
TI  - [Angle-closure glaucoma. Etiology and differential diagnosis].

PMID- 9578703
TI  - [Clinical evaluation of factors VIII and IX manufactured in Hungary, based on
      results of the first half year].
AB  - The development of anti-factor VIII/IX antibodies (inhibitor-induction) and the
      transmission of viral infections are the most significant complications of
      haemophilia treatment. The Humafactor-8 and Humafactor-9 are high-purity
      pasteurized factor VIII and IX concentrates, which are produced from pooled
      plasma of Hungarian donors by ion-exchange chromatography. The clinical study has
      been accomplished in two steps: first we have demonstrated the biological
      efficacy of the concentrates in a phase IV trial. After that we followed 13
      patients with severe haemophilia for 6 months in respect of virus-safety and
      inhibitor-induction. According to our results the recently developed domestic
      FVIII/FIX concentrates display appropriate biological activities and they are
      safe as blood-borne virus-transmission and immunogenicity are concerned.

PMID- 9578702
TI  - [Surgical trauma induced by laparoscopic cholecystectomy].
AB  - The objective demonstration of improved postoperative recovery suggests that
      surgical injury induced by the laparoscopic approach is less intense than that
      after open surgery. Forty-two patients diagnosed as having noncomplicated
      gallstones were studied prospectively. They were operated on by laparoscopy (LC,
      n = 21) or open surgery (OC, n = 21). Both surgical procedures induced
      significant changes of investigated parameters (acute-phase response, free
      radical mediated reactions, neutrophil functions). Comparison of the results of
      the two cholecystectomy techniques showed that laparoscopic cholecystectomy
      induced a significantly less intense acute-phase response, a more attenuated
      oxidative stress characterising by free radical mediated reactions and that is
      less disruptive to neutrophil function. The results and the data from the
      literature suggest that surgical injury causing by the laparoscopic
      cholecystectomy is less intense than that after open cholecystectomy, which can
      explain partially the better clinical outcome following laparoscopic versus open
      procedure.

PMID- 9578705
TI  - [Prognostic markers in the histopathological diagnosis of tumors of the choroid
      plexus].
AB  - Markers of cell proliferation (MIB-1), differentiation (S-100 protein,
      cytokeratin, transthyretin, GFAP, EMA, CEA), and cell adhesion (CD44) were
      analyzed immunohistochemically in a biopsy series of 21 chorioid plexus tumors
      determine their correlation with histological grade and impact on clinical
      course. The material included 8 papillomas (WHO grade I) and 8 carcinomas (WHO
      grade III); another 5 tumors were tentatively classified as atypical papilloma.
      The MIB-1 labeling index of papillomas was 3.7%, while that of carcinomas was
      14%. Atypical papillomas (mean: 6%) failed to segregate as a statistically
      different group. The age and sex of patients, and tumor localization were found
      not to influence MIB-1 reactivity. High MIB-1 labeling indexes were associated
      with less favourable postoperative outcome. S-100 protein immunoreactivity was
      generally reduced in carcinomas, while most tumors were positive for
      transthyretin and cytokeratin irrespective of their MIB-1 status. Positivity for
      GFAP and EMA was detected in some tumors of both low- and high grade. CEA was
      universally negative. The standard isoform of CD44 was only expressed in atypical
      papillomas and 4 carcinomas showing focal infiltration of adjacent tissues.
      Western-blot analysis was also carried out in 5 cases to detect CD44.
      Quantitation of MIB-1 immunohistochemistry may, thus, prove a more readily
      accessible ancillary method for assessing chorioid plexus neoplasms than analysis
      of differentiation markers. Our data also suggest that expression of CD44H is
      instrumental in conferring invasive potential to these tumors and possibly
      contributes to tumor progression as well.

PMID- 9578704
TI  - [Incidence of familial defective apolipoprotein B-100 in cases of patients
      diagnosed with familial hypercholesterolemia].
AB  - Familial Hypercholesterolemia (FH) and Familial Defective Apolipoprotein B-100
      (FDB) are monogenic, autosome, dominantly inherited diseases appearing as type
      II/a primary hypercholesterolemia. The frequency of the heterozygositic forms is
      1:700-1:500 in European population. Both forms of hypercholesterolemia causes
      early onset coronary heart diseases (CHD). According to the recommendations of
      the international MED-PED program (Make Early Diagnoses--Prevent Early Death), we
      found 73 FH cases and their 377 first relatives (parents, siblings, children)
      were also assessed. 156 patients were diagnosed clinically FH (131 alive and 25
      deceased), and 31.8% of the males and 32.4% of females suffered from early onset
      CHD. One family with FH consists of 5.46 members on the average and there are
      2.39 FH patients in one family. In our FH cohort four patients with FDB (R3500Q
      mutation) were diagnosed with allelspecific PCR, and the mutation was detectable
      also in 9 cases out of 11 living family members. The plasma total cholesterol
      level of the FDB patients--especially at younger age--was very close to the
      normal values, which is in contrast to the findings in FH patients. Nevertheless,
      FDB can be one of the independent causes of the early onset CHD. Therefore, in
      families with high frequency of cardiovascular diseases the R3500Q mutation has
      to be considered.

PMID- 9578706
TI  - [Severe left heart developmental disorder and severe fetal arrhythmia in the same
      family--a coincidental association?].
AB  - The etiology, pathogenesis and risk for inheritance of congenital heart
      abnormalities are important questions. The development of fetal echocardiography
      and fetopathology helped in examination of this problem. Between September 1992
      and June 1997 there were found four families where one member of the family had
      hypoplastic left heart syndrome and other member sustained fetal arrhythmia. The
      familiarity of hypoplastic left heart syndrome and some special forms of
      arrhythmias are well known. The reported familial association of these two
      abnormalities which in the first in the literature, may have a possibility that a
      sustained ectopic atrial arrhythmias are as severe risk factors for left heart
      abnormalities as other left heart abnormalities are.

PMID- 9578707
TI  - [The question of necessity of autopsies].

PMID- 9578708
TI  - [Is there a Society for Internal Medicine in Germany?)].

PMID- 9578709
TI  - [Aggression and the psychic self].
AB  - In this paper we explore the idea of aggression as a defence against threats to
      the psychological self. This aspect of the self allows reflection about people in
      psychological terms and develops, in the first three years of life, through
      appreciation of mental states in the other. When the object is unpredictable or
      hostile, recognition of this is painful to the child, and his reflective function
      will not be adequately established. The defences of aggression or avoidance will
      be invoked very frequently. In time, aggression may become an organising
      influence in the construction of the self; pathological destructiveness then
      takes the place of emotional relatedness and concern for the other.
      Psychoanalytic treatment no longer works primarily by addressing conflict.
      Instead, particularly through interpretations of transference and
      countertransference, the analyst recreates an intersubjective process which
      enhances the patient's reflective self, this time in the safety of a benign
      relationship.

PMID- 9578710
TI  - [Conversion symptoms in childhood and adolescence].
AB  - Since its first definition 100 years ago, the term conversion underwent many
      changes, a fact that is proved by various re-evaluations with respect to
      classification (DSM-IV, ICD-10). In the context of a psychodynamically-oriented
      diagnostic there are--in addition to that--actual attempts to reach a valid
      operationalization of the conversion concept. From a psychodynamic point of view
      a differentiation of traditional concepts has been made. Results of examinations
      of 45 children and adolescents (average age: 14 years, range: 8-18 years) who had
      been treated in the Department of Child and Adolescent Psychiatry of the
      University of Essen for conversion symptoms, revealed a strong interaction of
      oedipal and pre-oedipal conflicts and that in case that there was no help from a
      third object during early triangulation, the child's endeavor to break out of the
      primordial relationship with the primary love object had been impeded and thus
      individuation processes were impaired or even prevented. Our results lead to the
      conclusion that for the young patients, who came to us with a conversion symptom,
      the early pre-oedipal triangulation failed and thus primary separation and
      dependency conflicts could not be solved adequately.

PMID- 9578711
TI  - [Counseling, psychotherapy or psychological counseling? On the profile of
      therapeutic work in child guidance counseling].
AB  - The children's and young people's assistance law authoritatively pointed out more
      clearly, what counselling in educational guidance services offered by the youth
      welfare can be. Then a difference is to be made between psychotherapy as a free
      offer made by educational guidance services and psychotherapy as a service
      offered by the medical care system and financed by the health insurance.
      Important criteria for discrimination can be deduced from the purposes of the
      children's an young people's assistance law and from their interpretations. The
      law demands a stronger pedagogical orientation, and it even demands an
      orientation towards underprivileged groups dealing with everyday matters. An
      analysis of the current practice confirms this trend. Meanwhile the educational
      guidance services have developed an independent methodology. Much more than the
      therapy offered by the medical care systems this therapy is marked by pragmatic
      purposes and a generic orientation. This therapy is getting more and more
      profiled on the basis of the children's and young people's assistance law still
      is lacking however a theory bringing it forward as well as systematics studies of
      their effects.

PMID- 9578712
TI  - [The development of family therapy concepts--interrelationship between patients'
      and therapist's family].
AB  - During the last 20 years family therapy has well been established as a
      supplementary or alternative therapy to individual therapy within child and
      adolescent psychiatry. Along with the further development and the change of
      concepts of family therapy there has been a greater interest in the
      interrelationship within the triad of patient-family-therapist, too. In the
      training of family therapists the meaning of the family of origin has been
      recognized. The implications of the therapeutic professional activities on the
      psychiatrist's family has not yet thoroughly considered, however. In the present
      paper the development and the characteristics of some main concepts of family
      therapy are described. Illustrated by a case report the influences of family
      oriented therapeutic activities over the therapist's family are presented.
      Finally the interrelationship between the patient's and the therapist's family
      are discussed as a constructive element of a mutual learning process.

PMID- 9578713
TI  - [The Sceno Game in the course of time].
AB  - This article describes 50 years of working with the Sceno test, the first decades
      being in close cooperation with Gerhild von Staabs. After many years experience
      with the Sceno test in Swiss psychiatric hospitals over 1000 Sceno test games
      were conducted in the psychosomatic ward of the University of Munich Outpatient
      Department for Children and evaluated with a special record and slides. These
      were games carried out by children and adolescents with behavioral disorders,
      psychosomatic illnesses, and handicaps, in some cases by their mothers in an
      accompanying simultaneous analysis. Using the projective method the initial Sceno
      test, vulgar and original answers, key situations, repetition and memory
      compulsions were recorded. With 100 adults diagnosed as being schizophrenic Sceno
      tests with chaotic apparent order analogous to pictures painted by schizophrenics
      were observed. With adults and children with cerebro-organic damage we found an
      "organic play syndrom" in the game structure. Six medical dissertations dealt
      with the psychosomatics of children. Along with the depth psychology problems, in
      principle, the formality of the Sceno test set-up depending on age and
      development phase of the child also has to be taken into consideration. The Sceno
      test in its original form has proven itself to be up to date even today and
      requires only minor changes to some game elements, adapting them to the modern
      surroundings of children which means that a Sceno-R (Fliegner 1995) with 23 new
      game elements seems unnecessary. Psychodiagnostics and psychotherapy of our Sceno
      test game are based on the analytical method of Hans Zulliger and Anna Freud.

PMID- 9578714
TI  - Interleukin-2 reverses the defect in activation-induced apoptosis in T cells from
      autoimmune lpr mice.
AB  - Activated T cells from MRLlpr/lpr (lpr) mice have been shown to be resistant to
      TCR-induced apoptosis (activation-induced cell death) in vitro. We have found
      that this resistance is related to a defect in IL-2R alpha (CD25) expression and
      IL-2 signaling. Following primary activation, splenic T cells from 8-week old lpr
      mice failed to undergo apoptosis after the TCR was religated upon reculture with
      plate-bound anti-CD3 mAb. These cells had markedly reduced levels of IL-2
      secretion and CD25 expression during primary activation in vitro; however, the
      cells still progressed through the cell cycle and were capable of cell division
      following TCR religation. Addition of exogenous IL-2 during the primary
      activation of 8-week-old lpr T cells overcame the defect in CD25 expression.
      Strikingly, these cells also became sensitive to apoptosis induction and died
      when the TCR was religated with anti-CD3 mAb. Viable cell recovery of both the
      lpr CD4+ and CD8+ subsets, as well as the CD4-CD8- subsets, was dramatically
      reduced under these conditions. Further investigation also revealed that the
      defect in activation-induced apoptosis in T cells from lpr mice was age-related.
      Activated T cells from young lpr mice (5 weeks old) underwent apoptosis in
      response to TCR ligation; these cells also expressed normal levels of CD25
      following primary activation. However, as the mice aged from 5 to 8 weeks,
      susceptibility to TCR-mediated apoptosis in vitro was progressively lost together
      with the ability to express CD25. Our results suggest that before the onset of
      severe lymphoaccumulation, activated T cells from young lpr mice possess the
      capability to undergo TCR-induced apoptosis despite defective fas expression; IL
      2 participates in sensitizing the cells to this death pathway. In older mice,
      this pathway breaks down and, together with the lack of fas-induced apoptosis,
      may account for the onset of severe lymphoaccumulation and autoimmunity.

PMID- 9578715
TI  - Cyclic adenosine monophosphate inhibits nitric oxide-induced apoptosis in human
      leukemic HL-60 cells.
AB  - Previously we reported that phorbol ester, a protein kinase C (PKC) activator,
      exhibits a unique pattern of potentiation of nitric oxide (NO)-related apoptosis
      in HL-60 human promyelocytic leukemia cells. Here we show that elevation of
      intracellular cAMP could protect HL-60 cells from NO- or NO plus PMA-induced DNA
      damage. Exposure of cells to sodium nitroprusside (SNP; 0.5 to 4 mM), a NO
      generating agent, induced apoptotic cell death as monitored by morphological
      means, gel electrophoresis, and in situ TdT-apoptosis assay. However, concomitant
      incubation of the cells with DB-cAMP markedly inhibited SNP-induced apoptotic
      cell death in a dose-dependent manner. Similar results were obtained with other
      commonly used cAMP analogs such as CPT-cAMP and 8-C1-cAMP and the intracellular
      cAMP-elevating agent such as forskolin. In contrast, pretreatment of HL-60 cells
      with H89 or KT5720, which are known to inhibit cAMP-dependent protein kinase
      (PKA), abolished the protective effect of cAMP analogs and forskolin on SNP
      induced apoptosis. Synergism between SNP and phorbol ester to induce apoptosis
      was also inhibited by prior treatment of HL-60 cells with DB-cAMP or forskolin.
      The effect of DB-cAMP in maintaining cell viability was not associated with the
      onset of G0/G1 cell cycle arrest. In addition, neither dimethyl sulfoxide nor
      retinoic acid (which produce granulocyte differentiation) could produce cAMP
      effect. Under the same conditions, DB-cAMP also inhibited NO- or NO plus phorbol
      ester-induced apoptosis in another transformed cell line, U-937 cells. Taken
      together, these findings suggest that exposure of HL-60 cells to cAMP analogs
      renders them more resistant to NO-induced DNA damage and further suggest the
      existence of specific down-modulatory mechanisms related to NO-induced apoptotic
      DNA fragmentation.

PMID- 9578716
TI  - Induction of systemic lupus erythematosus-like disease in mice by immunization
      with heparan sulfate.
AB  - Experimental systemic lupus erythematosus (SLE)-like disease was induced in
      BALB/c mice by immunization with heparan sulfate, the major glycosaminoglycan of
      glomerular basement membrane. Following booster injections with heparan sulfate
      (HS), high levels of anti-HS, anti-dsDNA, and anti-cardiolipin antibodies were
      detected in the sera of the immunized mice. An enzyme-linked immunospot (ELISPOT)
      assay indicted that IgG anti-HS and anti-dsDNA antibody-secreting cells were
      present in the kidneys and most likely contributed to antibody localization.
      Antibodies eluted from the kidneys of immunized mice were found to react strongly
      with HS and dsDNA when tested in vitro. The HS-immunized mice developed moderate
      to severe levels of proteinuria. Histologic examination of kidneys from HS
      immunized mice revealed deposition of immunoglobulin in the kidneys. Our results
      describe the induction of SLE-like disease in normal mice following immunization
      with HS. This experimental model may be useful for understanding the immunologic
      basis for autoimmunity to HS.

PMID- 9578717
TI  - Inductive role of fibroblastic cell lines in development of the mouse thymus
      anlage in organ culture.
AB  - Previously, we have shown that embryonic day 12 thymus anlage cultured alone
      cannot develop into the mature organ but degenerates. In the present study, we
      investigated the cause of this insufficient organogenesis of embryonic day 12
      thymus anlage in organ culture. We cocultured embryonic day 12 thymus anlages
      with various cell lines as pellets formed by centrifugation. In coculture with
      fibroblastic cell lines, but not with thymic epithelial cell lines, embryonic day
      12 thymus anlages developed to support full T cell differentiation, and expressed
      mature stromal cell markers, Ia and Kb. By pellet culture of thymus anlages and
      fibroblastic cell lines transfected with a beta-galactosidase expression vector,
      we analyzed the distribution of added fibroblastic cells in pellets. The added
      fibroblastic cells constituted neither thymic capsule nor septa but disappeared
      after about 2 weeks in culture. Moreover, immunohistochemical studies indicated
      that added fibroblastic cells were adjacent to mesenchymal cells of thymus
      anlage. Our results strongly suggest that added fibroblastic cells support the
      development of the thymus anlage through interaction with its mesenchymal cells.

PMID- 9578718
TI  - Quantitative defect in staphylococcal enterotoxin A binding and presentation by
      HLA-DM-deficient T2.Ak cells corrected by transfection of HLA-DM genes.
AB  - HLA-DM facilitates peptide acquisition by MHC class II proteins within the
      endosomes of APC by facilitating release of invariant chain peptide intermediates
      (CLIP) from the class II molecules. T2 cells have a deletion in the MHC II region
      which deletes HLA-DM and MHC II genes. T2 cells transfected with MHC class II
      proteins are defective in protein presentation, a defect that is corrected by HLA
      DM transfection. Here we show that T2 cells transfected with Ak are also impaired
      in binding and presentation of the superantistaphylococcal enterotoxin A and that
      HLA-DM transfection corrects this defect. The poor ability of SEA to bind to Ak
      on DM-deficient cells is somewhat surprising since Ak has a low affinity for CLIP
      and is not predominantly occupied with CLIP on T2 cells compared to wide-type
      APC. These data suggest an influence of HLA-DM on the structure or composition of
      the Ak/peptide complex beyond its role in the release of invariant chain
      peptides.

PMID- 9578719
TI  - Antigen presentation by B7-nonprofessional APC does not prevent responses to
      solid tumor cells.
AB  - The growth of tumors in vivo often is associated with immune suppression. In this
      report we tested whether the expression of a known antigen by tumor cells would
      inhibit the development of antitumor responses when the antigen was subsequently
      expressed in an immunogenic form. For this, we expressed a well-characterized
      surrogate tumor antigen, the nucleoprotein (NP) of the PR8 virus, in solid tumor
      cells. Although the NP+ tumor cells were not rejected in vivo and stimulated
      nondetectable CTL response in vitro, T cells from these mice differentiated into
      CTL following i.p. inoculation of PR8 virus and their tumors regressed. The
      results suggested that prior presentation of tumor antigens by tumor cells does
      not necessary preclude a response if the peptide is subsequently presented
      appropriately.

PMID- 9578720
TI  - Enhanced engraftment of human peripheral blood lymphocytes into anti-murine
      interferon-gamma monoclonal antibody-treated C.B.-17-scid mice.
AB  - To improve the engraftment of human peripheral blood lymphocytes (PBL) to severe
      combined immunodeficient (SCID) mice, and to elucidate the factors which prevent
      the PBL's survival, we treated SCID mice with mAb, which neutralizes murine IFN
      gamma's ability to activate cell-mediated immunity. Compared with untreated mice,
      mAb-treated mice retained significantly higher numbers and ratios of human PBL in
      the peritoneal cavity and spleen, as well as significantly higher serum titers of
      human IgG and IgM. Histologically, host versus graft reaction (HVGR) was less
      severe in the mAb-treated mice. Moreover, these phenomena were completely
      abrogated when mice were also treated with murine recombinant IFN-gamma. These
      results suggest that murine IFN-gamma plays an important role in the rejection of
      human cells in SCID mice and that its depletion by means of mAb treatment can
      significantly reduce HVGR and improve the engraftment of human PBL.

PMID- 9578721
TI  - The density of the class II MHC T cell receptor ligand influences IFN-gamma/IL-4
      ratios in immune responses in vivo.
AB  - Activation of CD4+ T cells depends on T cell receptor recognition of MHC class
      II/peptide and on costimulation provided by CD28/B7. It has been shown that
      different levels of costimulation can influence T helper cell differentiation
      into Th1 versus Th2 phenotypes. Similar arguments have been made for different
      levels of peptide/MHC density on antigen-presenting cells, but to date supportive
      evidence has only come from in vitro studies. Here, using transgenic mice with
      reduced MHC class II expression on both B cells and dendritic cells, we
      demonstrate that T helper cell differentiation in vivo is also influenced by the
      density of expression of MHC class II. Although priming and expansion of antigen
      specific T cells were normal in these mice, T cell responses were dominated by
      the Th1-associated cytokine IFN-gamma, with reduced levels of the Th2 cytokine IL
      4 compared to controls. These results provide direct evidence that the efficiency
      of antigen presentation in vivo can determine effector cell phenotype.

PMID- 9578722
TI  - [Multifactorial model of estrogen synthesis in tumor tissue of breast cancer].

PMID- 9578723
TI  - [Blood coagulation disorders in cancer patients].

PMID- 9578724
TI  - [Carcinogenesis induced in experimental animals by inserting a synthetic
      pyrimidine base of 5-bromo-2'-desoxyuridine in the DNA].

PMID- 9578725
TI  - [Fatty acid oxidation products in food and tumor growth].

PMID- 9578726
TI  - [Biochemical and immunologic analysis of pepsinogen I in blood serum and mucosa
      in patients with gastric tumors and non-tumor diseases].
AB  - The results of the biochemical and immunologic studies of pepsinogen I (PG-I)
      occurring in the mucosa and blood serum of patients with tumors and non-tumor
      conditions of the stomach are discussed. Pepsinogen I was identified in human
      blood serum using rabbit antibodies against PG-I. Sharp drop in blood serum-PG-I
      level in patients with gastric tumors has been confirmed.

PMID- 9578727
TI  - [Cloning of amplified nucleotide sequences of DNA in a patient from a high-risk
      stomach cancer family].
AB  - An abnormally long shorter shoulder of chromosome 21 was identified in 3 out of 4
      members of a family at high risk for gastric cancer. We attempted to clone the
      amplified fragments of DNA of one of the family members who had the same
      chromosomal marker. This was done after the amplified sequences were enriched by
      re-association in phenolic emulsion, and 52 clones were obtained. All inserts
      were separated and each was hybridized on filters containing Hind III DNA of
      patient O.L. and that of a healthy donor. Hybridization with the genome DNAs of
      patient O.L. and the donor failed to go through in 9 inserts. Hybridization with
      all genomic DNAs went through in 34 inserts. Hybrids with one or several Hind III
      fragments of DNAs of O.L. and the donor were formed in 9 inserts. The size of
      fragments with varying molecular weight in inserts 6, 9, 11, 30, 39, 43 and 44
      identified in the DNA of patient O.L. was 3-10 times that in the DNA of the
      donor. The differences in the molecular weight and size of the detected bends
      seem to indicate that we succeeded in cloning at least several different
      amplified fragments of the genome of the patient.

PMID- 9578728
TI  - [S allele of the L-myc oncogene is associated with lung cancer metastases in
      patients from Moldova].
AB  - Race is widely believed to be a factor in the relationship between S allele of L
      MYC oncogene and disseminated lung cancer. In particular, the clinical
      significance of L-MYC genotype was demonstrated in the Japanese while the results
      for the white US, Australian and Norwegian cohorts were negative. The present
      study was concerned with distribution of L-MYC oncogene alleles in 43 patients
      with lung cancer and 77 healthy subjects in Moldova. L and S allele frequency in
      both groups were nearly identical. However, the SS genotype was registered much
      more frequently in patients with metastasis (10/28; 36%)(p < 0.05) than in those
      with localized tumor (0/12). Moreover, overall frequency of S allele was
      significantly higher in lung cancer patients with node involvement (35/56; 63%)(p
      < 0.02) than in those with localized tumors (8/24; 33%)(p < 0.02). Finally, a
      significant correlation was found between S allele occurrence and distant
      metastases (M1: 19/28; 68%; M0:26/58; 45%)(p < 0.05). Similar data were reported
      in Russia. (ABSTRACT TRUNCATED)

PMID- 9578729
TI  - [Correlation between tumor tissue aromatase, histological pattern and
      reproductive status in patients with breast cancer].
AB  - Aromatase levels were measured in tumor tissue vis-a-vis clinico-morphological
      patterns of tumor, menopausal status and sex hormone concentration in blood in 50
      patients with breast tumors. The test was based on heavy water release from 1
      beta-3H-androstenedione. Direct correlation was established between aromatase
      concentration, on the one hand, and tumor size, cell differentiation status and
      blood-testosterone on the other. The data point to the role of aromatase
      concentration in situ during breast tumor genesis, its dependence on hormonal
      environment of tumor and its presence in breast tumor cells.

PMID- 9578730
TI  - [Blood insulin and insulin sensitivity in breast cancer patients of various ages:
      the effect of smoking].
AB  - Blood-glucose and insulin were assayed by administering 40 g/sq.m glucose (per
      os) and 0.08 unit/kg body weight in 113 patients with early-stage breast tumors
      (glucose-tolerance test) and in 62 patients (insulin-sensitivity test).
      Sensitivity to insulin was assessed versus age, reproductive status, body size
      and smoker/non-smoker status. A direct correlation between high level of reactive
      insulinemia and obesity and an inverse one--between sensitivity to insulin and
      age were established on the basis of insulin test data and the insulin resistance
      factor. Smokers showed, on the average, lowered basal insulin levels and
      increased sensitivity to insulin (depending on age and number of cigarettes
      consumed). Smoking was found to influence prolactin reaction to hypoglycemia and
      to upset the correlation between age and progesterone receptor concentration in
      tumor which may account for certain peculiarities of the course of the disease in
      smokers with breast tumors.

PMID- 9578731
TI  - [Immunohistochemical study of the proliferation of breast cancer cells based on
      the expression of proliferating cell nuclear antigen (PCNA)].
AB  - Proliferative activity was estimated in 10 benign lesions and 47 cancers of
      mammary gland (mainly, invasive ductal carcinomas), and 14 metastatic lymph nodes
      by means of immunohistochemical determination of PCNA. Total PCNA expressing
      nuclei (PCNAtot) and nuclei strongly stained (PCNAstr) were counted.
      Proliferation index (PI) measured by counting PCNAstr nuclei has a higher
      correlation (r = 0.94, p < 0.000000) with PI estimated by means of 5-bromo-2
      desoxyuridine in vivo than that obtained by counting PCNAtot nuclei (r = 0.77, p
      < 0.000000). Total and strong PCNA expression increased significantly when graded
      according to H.J.G. Bloom & W.W. Richardson. There is a clear correlation between
      PI of primary breast cancer and its metastases in lymph nodes (r = 0.89, PCNAtot
      and r = 0.90, PCNAstr), but proliferative activity in metastases was
      significantly lower than that of in primary tumors (p = 0.02 and p = 0.003). PCNA
      expressing tumor cells is a method of evaluation of proliferative activity in
      tissues which permits using archival paraffin samples.

PMID- 9578732
TI  - [Comparative study of the ploidy and cell proliferation of malignant epithelial
      neoplasms of various origin (flow cytometric assay)].
AB  - Flow cytometry was used for measure DNA content of tumor cells of squamous-cell
      carcinoma of the tongue and mucosa of the oral cavity fundus, invasive ductal
      breast carcinoma, endometrial, colonic and rectal adenocarcinomas. Frequency of
      aneuploidy is characteristic of tumor. Frequency of aneuploidy is high in the
      oral cavity and breast cancer, colonic and rectal carcinomas and low in cancer of
      the tongue and endometrium Aneuploidy is associated with nonfavorable clinical
      and morphological signs of breast cancer, carcinomas of the oral cavity, corpurus
      uteri and rectum. High DNA index is typical of aggressiveness of carcinomas of
      the tongue, breast and endometrium. High proliferative activity prognostic factor
      of endometrial adenocarcinoma. We also found aneuploid cells in normal epithelium
      of the corpurus uteri, colon and rectum of patients with aneuploid tumors of the
      same organ. It is possible to suggest that these cells is an unfavorable cause
      recurrence.

PMID- 9578733
TI  - Assessment of benz(a)pyrene pollution in the flood area of the Luga river.
AB  - Benz(a)pyrene pollution levels have been identified in the soils and vegetation
      of the flood plains of the River Luga, Leningrad Region. Maximum pollution
      exceeding background levels 2-10 times (11.02-52.71 mkg/kg) was detected in the
      soils around the towns of Luga and Kingisepp. The benz(a)pyrene levels in the
      vegetation (2.04 mkg/kg) were below background values. No significant correlation
      was established between the concentrations of pollution in the soil and
      vegetation. Our data suggest that the area of the mid-course of the River Luga
      should be preserved as a natural habitat of the plants of the Poaceae family.

PMID- 9578734
TI  - [Effect of computer terminal irradiation on mice prior to mating on tumorigenesis
      in the offspring].
AB  - Male and female SHR mice were exposed to irradiation from the display terminal of
      a personal computer, 1 hr, 5 times a week for 2 weeks. Then the animals were
      mated and tumor yield in the progeny was studied. The descendants of intact mice
      were used as control. A significant increase in total tumor incidence was
      recorded in males and females in the experimental group. Adenocarcinoma of the
      mammary gland highly featured in females while lung tumors--in males.

PMID- 9578735
TI  - [New means for the prophylaxis of colon cancer with the use of beta-glucuronidase
      inhibitors].
AB  - Experiments involving the use of 1,2-dimethylhydrazine-induced colonic tumors in
      rats showed long-term treatment with a newly synthesized drug EDE-10g to inhibit
      an enzyme of enteric beta-glucuronidase, to suppress carcinogenesis and to
      prolong lifespan of animals.

PMID- 9578736
TI  - [Effect of the enterosorbent Aqualen on intestinal carcinogenesis induced by 1,2
      dimethylhydrazine in rats].
AB  - Subcutaneous injections of 21 mg/kg 1,2-dimethylhydrazine were given weekly to
      134 female LI0 rats. In the first series, 73 rats received 15 injections while 63
      animals--5 injections (series 11). Some rats were also fed Aqualen (0.1 or 1.0
      g/kg b.w.) during the whole experiment (6 months). In run 1, all animals
      developed malignant tumors of the colon. However, multiple tumors in Aqualen-fed
      rats were significantly less frequent than in those receiving carcinogenic agent
      alone. Also, Aqualen appeared to inhibit the development of carcinoma in the
      small intestine. In run 11, Aqualen treatment was followed by decreased incidence
      and multiplicity of tumors both in the entire large intestine and ascending and
      descending colon. Rectal tumor incidence was lower, too. In both runs, tumor size
      in enterosorbent-fed animals was smaller than in controls. All intestinal tumors
      were adenocarcinomas. No pathology was observed in Aqualen-fed rats untreated
      with the carcinogenic agent.

PMID- 9578737
TI  - [The inhibitory effect of water-soluble and liposomal beta-carotene on various
      models of carcinogenesis].
AB  - The inhibitory effects of the newly-developed forms of beta-carotene--water
      soluble and liposomal--have been studied in rats and mice bearing tumors induced
      in 4 models of carcinogenesis. Mammary tumors were induced by single injections
      of 1 mg methylnitrosourea into each gland. Esophageal tumors were induced in male
      rats by intragastric administration of 3 mg/kg methylbenzylnitrosoamine, thrice a
      week for 4 weeks. Tumors of the vagina and cervix uteri were induced by
      intravaginal painting with 25 mkg dimethylbenz(a)anthracene, twice a week for 6
      weeks. Tumors of the lung were induced in female mice by intraperitoneal
      injection of 1 g/kg urethane, once a week for 6 weeks. With models I-III, animals
      received water-soluble beta-carotene (Aquiton-10) with drinking water (200 mg/I),
      on completion of carcinogen treatment and for another 9-12 months until the end
      of experiment. Urethane-treated mice received liposomal beta-carotene with
      drinking water (60 mg/l) 10 days before the beginning of carcinogen treatment and
      for another 6 months until the end experiment. Water-soluble beta-carotene failed
      to influence the carcinogenesis in the mammary gland and esophagus in rats;
      however, it significantly inhibited carcinoma development in murine vagina and
      cervix uteri (47.0%). Liposomal beta-carotene significantly inhibited lung
      adenomas (46.4%) and mammary carcinomas (55.6%) in urethane-treated mice.

PMID- 9578739
TI  - [Experimental study of the biopreparation Lymphotilin as an antiproliferative and
      antitumor agent].
AB  - We found in experiments involving the use of a biopreparation lymphotilin that
      its administration was followed by a decrease in proliferative activity of
      cultured tumor cells and a longer survival of mice bearing transplantable
      leukemia. An intensified intercalation of ethidium bromide in nucleic acids of
      tumor cells in lymphotilin culture points to the drug activity on nuclear level.
      Tumor cell inhibition by lymphotilin holds much promise for the practice of
      hematology.

PMID- 9578738
TI  - [Experimental tests and clinical trials of the biologically active food additive
      Fibromed].
AB  - A biologically active food additive--Fibromed--has been tested experimentally and
      clinically. The additive made from wheat bran by the Reacon Company contains no
      less than 40% of dietary fibre (cellulose, hemicellulose and lignin). Its effect
      on multi-organ carcinogenesis induced by N-methyl-N-nitrosourea (MNU) and lipid
      metabolism was tested in rats. Tumors were induced by combined intramammary
      injections and intrarectal infusions of the agent. Fibromed was fed (20% by
      weight) during post-initiation period. It effectively inhibited the development
      of mammary and colonic tumors and reduced serum-blood cholesterol, triglycerides
      and beta-lipoproteids. The influence of Fibromed treatment on stool during early
      post-operative period was studied in surgical cases of colorectal cancer. When
      administered in a dose of 60 g, daily, starting from days 4-5, Fibromed restored
      intestinal function 36 hr earlier than in controls. Fibromed should be
      recommended for prevention of breast and colonic tumors, lipid metabolism
      disorders and rehabilitation of patients who underwent surgery for colorectal
      cancer.

PMID- 9578740
TI  - [Alkyl nitrosoureidodioxans and alkyl nitrosoureidopropane diols -- new groups of
      antitumor compounds].
AB  - 1,3-dioxan- and 1,3-propane diol derivatives of alkyl nitrosourea have been
      synthesized and studied. Like other 2/chloroethylnitrosoureas, they exerted
      pronounced influence on a wide range of transplantable tumors, including those
      transplanted intracranially. Antitumor effect was found to depend on C5 and C2
      atom substituent in the 1,3-dioxan cycle and 1,3-propane diol, respectively. The
      therapeutic effect and toxicity of 1,3-propane diol derivatives were higher than
      those of 1,3-dioxan. The substances lost all antitumor properties if a methyl
      group was substituted for the 2-chloroethyl one, even though a nitroso group was
      retained in their structure.

PMID- 9578741
TI  - [Antitumor activity and toxicity of combined doxorubicin and disodium salt of
      methylene-1,1-diphosphonic acid].
AB  - In experiments using mice and rats with transplantable Ehrlich ascites tumors,
      sarcoma-180 and adenocarcinoma of Walker, antitumor activity of doxorubicin in
      combination with disodium salt of 1,1-methylenediphosphonic acid proved higher
      than that of doxorubicin alone. Most advantage was gained with daily treatment.
      The toxic effect of said complex treatment seemed to differ slightly from that of
      doxorubicin as judged on the basis of survival, changes in body mass and
      peripheral blood count.

PMID- 9578742
TI  - [Effect of carbon dioxide on peroxynitrite reaction with DNA].
AB  - Carbon dioxide has been reported to react with peroxynitrite (ONO2CO2-), altering
      the reactivity characteristic of peroxynitrite. We found that carbon dioxide
      caused a dose-dependent increase in 8-nitroguanine formation in calf thymus DNA
      incubated with peroxynitrite, whereas there was not apparent effect on 8
      oxoguanine formation. In contrast, carbon dioxide inhibited peroxynitrite-induced
      strand breakage in plasmid pBR322 DNA and thymine-propenal formation from
      thymidine.

PMID- 9578743
TI  - [Results of cytologic diagnosis of breast tumors].
AB  - The data on the cytological diagnosis of breast cancer in 4.410 patients tuated
      at the Clinic of the Institute in 1993-1996 are presented. There was histological
      evidence on 1,479 patients. The sensitivity of cytological examination was 97.2,
      specificity--92.4, predictive value of positive test--97 and that of negative
      test--93%. Correlations between cytological evidence, histological pattern, stage
      and size of tumor are discussed.

PMID- 9578744
TI  - [Cytologic diagnosis of retroperitoneal tumors in children].
AB  - Cytological diagnosis of retroperitoneal tumors in 173 children (1985-1996) has
      been evaluated, using aspiration biopsy (165), imprint smears (84) and
      cytohistological examination (128). Fine-needle biopsy data were confirmed in
      99%; histological examination--97.3%.

PMID- 9578745
TI  - [Fibroxanthoma of the stomach].

PMID- 9578746
TI  - [Biotherapy of solid tumors].

PMID- 9578747
TI  - [Do cell proliferation disorders play a crucial role in carcinogenesis?].

PMID- 9578748
TI  - Unguided bronchoalveolar lavage techniques and residual effects in dogs.
AB  - OBJECTIVES: To investigate the use of unguided bronchoalveolar lavage techniques
      in dogs without fibreoptic bronchoscopy, using an adapted single vascular
      catheter and a double-lumen catheter made from two single vascular catheters.
      ANIMALS: Sixty-nine dogs were examined with the single-catheter technique and 110
      dogs with the double-catheter technique. DESIGN: A prospective study. PROCEDURE:
      Sixty-nine and 220 samples, collected with the single catheter and the double
      catheter respectively, were examined cytologically. Lungs of 69 dogs were
      examined grossly and histologically. Radiographic examination was performed on 11
      dogs. RESULTS: The double-catheter technique produced samples with significantly
      higher cellularity (P < 0.01) and fewer red blood cells (P < 0.01) than the
      single-catheter technique. Repeat samples collected with a double catheter were
      not significantly different (P > 0.01) in any value. A reference range for
      nucleated cell counts of 62 to 1210 x 10(6)/L was calculated from 57 clinically
      and histologically normal dogs. The major residual effects of the technique were
      localised pulmonary oedema, and alveolar distension with collapse and congestion
      of distant parenchyma. Thoracic radiographs revealed increased lung opacity for
      at least up to 7 h after the procedure. CONCLUSIONS: The cellularity of the
      bronchoalveolar lavage fluid obtained was adequate and sufficient fluid was
      retrieved when the single catheter was located in a proper position. However, the
      double catheter obtained better samples more quickly and easily, with less damage
      to the respiratory tract.

PMID- 9578749
TI  - Diaphragmatic hernia in a goat.

PMID- 9578750
TI  - Cerebrospinal angiostrongyliasis in five captive tamarins (Sanguinus spp).
AB  - Four cotton-top tamarins (Sanguinus oedipus oedipus) and one emperor tamarin (S
      imperator subgrisescens) housed in a zoo became depressed, anorexic, paraparetic
      and eventually paralysed. The animals died within 5 days to 18 months of the
      appearance of clinical signs. Histological examination showed nonsuppurative and
      eosinophilic meningoencephalitis, and metastrongyle nematode larvae were found
      within subarachnoid spaces of all animals and within the spinal cord of one.
      Intact larvae with features consistent with Angiostrongylus cantonensis were
      recovered from the brain of one animal. This parasite is the classical cause of
      eosinophilic meningoencephalitis in many parts of the world and the diagnosis can
      be strongly suspected on clinical grounds. In endemic areas like south-east
      Queensland, protection of captive animals against infection with A cantonensis is
      a difficult balance between providing a stimulating, natural setting and
      eliminating potentially infectious definitive, intermediate and paratenic hosts.
      This is the first report of cerebrospinal angiostrongyliasis in tamarins and
      nonhuman primates in Australia.

PMID- 9578752
TI  - Drugs in racing.

PMID- 9578751
TI  - Investigation of osteochondrosis in grazing beef cattle.
AB  - Severe lameness attributed to osteochondrosis is described in an extensively
      managed Brahman herd grazing on improved native pasture. Clinical signs were
      observed in five animals, three of which were necropsied. The most prominent
      lesions were in the elbow and stifle joints. There were multiple fissuring and
      ulceration of thickened articular cartilage with numerous osteochondral bodies
      present in the joint spaces. All affected animals were entire males sharing a
      common ancestral sire. Inheritance and gender were suspected to be contributing
      factors in the development of the disease.

PMID- 9578753
TI  - Does the use of antibiotics in animals affect human health?

PMID- 9578754
TI  - Longitudinal study of career plans and directions of veterinary students and
      recent graduates during the first five years after graduation.
AB  - OBJECTIVES: To determine the patterns of work undertaken by veterinarians during
      the first 5 years after graduation, and to study the background to career
      decisions. DESIGN: Longitudinal study. POPULATION: Veterinarians (119) who
      started the veterinary course at the University of Queensland in 1985 and 1986,
      and who responded to a mailed questionnaire 5 years after they graduated.
      PROCEDURE: Questionnaires were completed in the first and fifth year of the
      veterinary course, and in the second and after the fifth year after graduation.
      The data were coded numerically and analysed using the SAS System for Windows.
      RESULTS: Most respondents (61%) planned to work in mixed practice and 61% entered
      mixed practice initially, but only 39% of these (26% of the total) remained in
      mixed practice after 5 years. Those who had grown up on a farm which derived
      primary income from animals were more likely to enter mixed practice, but half of
      this group had left mixed practice after 5 years. Most decisions to change career
      direction involved a move away from negative factors including inadequate private
      time and/or rewards, issues involving other people including the practice
      principal and sometimes clients, or aspects of the work itself. However, some
      cited positive reasons, including opportunities to learn, to help others or to
      travel. There were no significant differences between males and females in the
      numbers entering mixed practice or leaving it, or entering small animal practice,
      or in attitudes to many issues involving veterinarians. However, more females
      than males found their remuneration too small, and females did receive
      significantly smaller incomes than males. CONCLUSIONS: Most graduating
      veterinarians, especially those from farms with animals, seek to enter mixed
      practice initially. Negative experiences are mainly responsible for moves to
      small animal practice. Gender does not affect the distribution of young
      veterinarians between mixed and small animal practice.

PMID- 9578755
TI  - Effects of inflammation-associated acute-phase response on hepatic and renal
      indices in the horse.
AB  - OBJECTIVES: To determine the effect of an acute soft tissue inflammatory response
      on biochemical and haematological indices of hepatic and renal function in the
      Thoroughbred horse. PROCEDURE: Soft tissue inflammation was induced in four
      Thoroughbred horses by intramuscular injections of Freund's complete adjuvant.
      The horses were clinically examined and blood and urine samples were collected
      before and after the adjuvant injections. Biochemical and haematological indices
      were measured in samples collected and used to determine the onset of the acute
      phase response and to assess hepatic and renal function at this time. RESULTS:
      After adjuvant injection, significant increases (P < 0.01) in total white (13.1
      +/- 1.4 x 10(9)/L) and neutrophil (10.2 +/- 1.2 x 109/L) cell counts, rectal
      temperature (39.7 +/- 0.5 degrees C) and various plasma protein concentrations,
      including fibrinogen (6.6 +/- 1.2 g/L), haptoglobin (1.3 +/- 0.1 g/L) and total
      protein (88.1 +/- 2.7 g/L), indicated the induction of an acute-phase response.
      This corresponded with significant reductions (P < 0.01) in the plasma
      elimination half-lives (t1/2 beta) sodium bromosulphthalein (3.13 +/- 0.05 to
      2.82 +/- 0.07 min) and sodium sulphanilate (38.29 +/- 4.04 to 19.60 +/- 5.68 min)
      and reductions in the plasma activities of aspartate aminotransferase, glutamate
      dehydrogenase, creatine kinase, alkaline phosphatase, gamma glutamyl transferase;
      the urinary creatinine clearance ratios of sodium, chloride and potassium; and
      the urinary gamma glutamyl transferase-to-creatinine clearance ratios. (All
      values mean +/- SD.) CONCLUSIONS: The effects of the acute-phase response on
      indices of hepatic and renal function in the horse suggest that the disposition
      of pharmacological agents administered at this time may be altered and that
      indices of acute inflammation should be interpreted cautiously.

PMID- 9578756
TI  - Snake bites recorded by veterinary practices in Australia.
AB  - OBJECTIVE: To determine the extent of the snake bite problem in domestic animals,
      its regional significance and the effects of antivenom treatment. DESIGN: A
      questionnaire was designed seeking information on the number and type of domestic
      animals referred, whether treated or untreated, type of snakes and management of
      the bite. PROCEDURE: The survey form was sent to 10% of veterinary surgeons,
      selected at random throughout Australia. RESULTS: The response of 106 veterinary
      surgeons revealed that snake bite in domestic animals is frequent, with an
      estimated 6200 cases reported annually. Bites were more prominent in rural (78%)
      than urban areas (22%) with brown, tiger and black snakes accounting for 76%,
      113% and 6% of cases, respectively. Cats and dogs were the most frequently
      reported victims. Ninety-one percent of cats and 75% of dogs survived following
      the administration of antivenom whereas 66% of cats and 31% of dogs survived
      without antivenom. Overall, in 33% of cases antivenom was not used, and venom
      detection kits were used in only 1% of cases. A number of drugs were used in
      various combinations with or without antivenom and intravenous fluids in the
      treatment of animals with snake bite, but their role in reducing the severity of
      envenomations was not assessed. CLINICAL IMPLICATIONS: Antivenom significantly
      improves the chances of survival of domestic animals bitten by snakes.

PMID- 9578757
TI  - Chondrodysplasia in Australian Dexter cattle.
AB  - OBJECTIVE: To describe the occurrence of chondrodysplasia in Australian Dexter
      cattle. DESIGN: A pathological and genetic case report. PROCEDURE: Congenital
      lethal chondrodysplasia was studied in two female Dexter foetuses aborted mid to
      late gestation. Clinicopathological findings including histological changes in
      limb bones, and analysis of pedigree information were evaluated. RESULTS:
      Characteristic features of congenital lethal chondrodysplasia (Dexter bulldog)
      include abortion, disproportionate dwarfism, a short vertebral column, marked
      micromelia, a relatively large head with retruded muzzle, cleft palate and
      protruding tongue and a large abdominal hernia. Histological changes in limb
      bones are consistent with failure of endochondral ossification. Dexter
      chondrodysplasia is considered to be inherited in an incompletely dominant manner
      with the homozygous form producing the congenital lethal condition. A preliminary
      minimum estimate of heterozygote frequency is 19% within the registered
      Australian Dexter herd, based on analysis of the contribution of three obligate
      heterozygotes whose semen has been widely used by artificial insemination in
      Australia. CONCLUSION: Dexter chondrodysplasia is present in Australian cattle
      and further cases of the homozygous form, congenital lethal chondrodysplasia, are
      likely to occur. RECOMMENDATION: It is requested that spleen and liver tissue
      from bulldog foetuses and blood from their parents be collected to assist
      research into Dexter chondrodysplasia.

PMID- 9578758
TI  - Diabetes mellitus in a koala (Phascolarctos cinereus).
AB  - OBJECTIVE: To describe a case of diabetes mellitus in a koala (Phascolarctos
      cinereus). DESIGN: A case report with controls. PROCEDURES: We describe clinical
      and laboratory findings in a 6-year-old, free-living, female koala presented with
      traumatic injury and subsequently found to have polydipsia, hyperglycaemia and
      glucosuria. Over a 5 week period, serum biochemical analyses, haematological
      examinations, urinalyses, measurement of serum insulin and fructosamine
      concentrations, necropsy, histopathological examination of a range of tissues and
      immunohistochemical examination of the pancreas for insulin-containing cells were
      done. For reference purposes, serum insulin and fructosamine concentrations were
      determined in four and two healthy koalas, respectively, and three healthy
      koalas' pancreases were examined histologically and immunohistochemically.
      RESULTS: The koala had persistent hyperglycaemia, hyperlipidaemia, hyponatraemia,
      hypochloraemia and glucosuria. Serum insulin concentration of the diabetic koala
      was only marginally smaller than that of healthy koalas, but all concentrations
      were smaller than reference concentrations in dogs and people. Fructosamine
      concentration did not allow the diabetic koala to be distinguished from healthy
      koalas and concentrations of all koala analytes were greater than expected for
      healthy dogs and people. Histopathological examination revealed extensive
      degeneration of pancreatic islet cells and fatty infiltration of hepatocytes.
      Immunoperoxidase staining revealed decreased or absent insulin in the beta calls
      of the affected koala. CONCLUSION: Clinical signs, clinicopathological results
      and histopathological changes were consistent with diabetes mellitus. The
      pathogenesis of the condition could not be determined but may have been related
      to the administration of a parenteral corticosteroid preparation, the stress of
      capture or tissue damage and inflammation.

PMID- 9578759
TI  - Coccidia (Eimeria spp) of wild rabbits in southwestern Australia.

PMID- 9578760
TI  - More care needed with specimens.

PMID- 9578761
TI  - Cutaneous syndrome possibly caused by heartworm infestation in a dog.
AB  - A 9-year old German Shepherd bitch was presented with a recent onset of
      seborrhoea oleosa, hyperpigmentation, erythema, pruritus and alopecia along the
      neck, thorax, ventrum and the dorsal area of the carpus. The skin changes were
      believed to be caused by Dirofilaria immitis infection. A combination of topical
      and parenteral anti-heartworm therapy led to the resolution of the lesions.

PMID- 9578762
TI  - Outbreak of fibrinous pneumonia in recently weaned beef calves in southern
      Queensland.
AB  - OBJECTIVE: To describe an outbreak of fibrinous pneumonia in 331 recently weaned
      beef calves on two properties in the Miles district in southern Queensland.
      DESCRIPTION OF THE HERD: The affected calves came from three groups: 88 recently
      weaned calves purchased at Casino NSW saleyards on 29 April 1994, 91 recently
      weaned calves purchased at Inverell NSW saleyards on 11 May 1994 and 152 homebred
      calves weaned on 18 May 1994 off the owner's cows. All calves were Hereford and
      Hereford cross. INVESTIGATION: The two groups of purchased calves (the Casino
      Inverell weaners) were mixed together and moved to another recently purchased
      property on May 19 after handling on May 18. The homebred weaners were not mixed
      with the Casino-Inverell weaners, but had nose-to-nose contact for one night via
      a 3 m gateway while yarded on May 18. By May 25, an outbreak of acute
      undifferentiated bovine respiratory disease was evident among all 331 calves and
      two were dead. The morbidity risk in all three groups was 90%, suggesting the
      three groups of calves were equally susceptible. Five calves died during the
      outbreak, giving a crude mortality rate of 1.5% (5/331), with necropsy of three
      calves showing they died of fibrinous pneumonia. Treatment of all calves with a
      single injection of 20 mg/kg of long acting oxytetracycline lead to rapid
      clinical improvement in affected calves, and appeared to prevent further
      mortality. Mortality clustered, with three of the four dead purchased calves
      coming from one vendor of the Inverell sale. CONCLUSIONS: Fibrinous pneumonia can
      occur after weaning in beef calves in Australia. It is highly contagious among
      groups of recently weaned calves.

PMID- 9578763
TI  - Role of prokinetic drugs for treatment of postoperative ileus in the horse.
AB  - All horses undergoing coeliotomy for an acute abdominal crisis are at risk of
      developing ileus and should receive therapy aimed at promoting gastrointestinal
      function by restoring fluid and electrolyte balance. Adequate analgesia and
      prevention against peritonitis, bacteraemia and endotoxaemia should be provided.
      Horses that at the time of surgery have a strangulating or non-strangulating
      small intestinal obstruction should be considered to be at greater risk of
      developing a persistent ileus that is refractory to treatment than those horses
      with lesions involving the large intestine. In horses considered to be at greater
      risk of developing a persistent ileus, the use of prokinetic agents should be
      considered. Agents that may be used to improve gastrointestinal motility include
      adrenergic receptor antagonists, cholinergic agonists, benzamides, dopamine
      antagonists, macrolide antimicrobials, opiate receptor agonists and antagonists,
      somatostatin analogues and local anaesthetics. There are limited studies into the
      use of these agents in the horse. Until further research provides more
      information on motility disorders following intestinal surgery and the efficacy
      of prokinetic agents in this species, only selective use of some of these drugs
      can be recommended.

PMID- 9578764
TI  - Ovine Johne's disease.

PMID- 9578765
TI  - Severity and persistence of footrot in Merino sheep experimentally infected with
      a protease thermostable strain of Dichelobacter nodosus at five sites.
AB  - OBJECTIVE: To test the hypothesis that ovine footrot associated with a
      thermostable protease strain of Dichelobacter nodosus undergoes self cure or is
      sustained as an annually recurring disease, depending on the environment. DESIGN
      AND PROCEDURE: Forty Merino sheep from a single blood line were infected with a
      protease thermostable strain of D nodosus at each of five sites in Western
      Australia. Footrot lesions and microscopic evidence of D nodosus were recorded
      every fortnight for 2.5 years, supplemented by laboratory culture. Rainfall, soil
      and air temperature, pasture quantity and composition and soil types were also
      recorded. Flocks that apparently self cured were relocated to a more favourable
      site for footrot in the final spring season. RESULTS: The maximum prevalence of
      feet with clinical footrot lesions was 80.6, 1.3, 14.4, 3.8 and 88.1% at the five
      sites. Severe footrot occurred for three consecutive spring seasons at one site
      that had clay loam soil and at least 3500 kg/ha total pasture dry matter
      annually. However, the infection was asymptomatic for up to 10 weeks between
      outbreaks. D nodosus was isolated from flocks for 2.5 years at only two sites,
      although there was microscopic evidence of the organism at other sites in the
      final year. A thermolabile variant (strain U6) of D nodosus was isolated from the
      two sites where footrot persisted. CONCLUSION: Depending on time and location,
      ovine footrot induced by a protease thermostable strain of D nodosus either self
      cured or persisted as annual outbreaks interspersed with periods of asymptomatic
      infection.

PMID- 9578766
TI  - Field trials evaluating ivermectin controlled-release capsules for weaner sheep
      and for breeding ewes.
AB  - OBJECTIVE: To confirm the efficacy of ivermectin released from a controlled
      release capsule administered to young sheep and to breeding ewes under field
      conditions. DESIGN: Randomised field trials. PROCEDURE: In each of ten field
      trials 25 weaned lambs were treated with ivermectin controlled-release capsules
      and 25 remained untreated. Eight similar field trials were conducted using adult
      ewes. Efficacy against infections of gastrointestinal nematodes was assessed by
      faecal egg counts and faecal larval culture. Body weights were recorded and
      faecal soiling of the breech wool (dags) was assessed. RESULTS: Nematode faecal
      egg counts in the two groups were not different (P = 0.13) before treatment in
      the weaner trials or before treatment in the ewe trials (P = 0.49), but
      thereafter eggs in the untreated sheep persisted, whereas counts in sheep given
      capsules were negligible (P < or = 0.01). In the weaner trials, dag scores for
      the two groups were not different at the start of the trials (P = 0.18) but at
      the end, untreated sheep had significantly more dags (P = 0.04) than treated
      sheep. In the ewe trials, dag scores remained low in both groups. Weaners treated
      with the capsule gained 1.4 kg (95% CL: 0.7, 3.1) more weight over the 16 week
      trial period compared to untreated weaners (P = 0.01). Both groups of ewes lost
      weight as a result of parturition but the mean loss by week 16 was greater for
      untreated (3.7 kg) (95% CL: -5.1, -2.2) than for treated ewes (1.8 kg) (95% CL: 
      3.3, -0.4). The mean change in ewe body weight for the two groups was however not
      significant (P = 0.07). Differentiation of nematode larvae recovered from
      cultures of faeces from untreated animals indicated that the capsules were
      effective against the common parasites of sheep. CONCLUSION: The capsule was
      efficacious against gastrointestinal nematodes judging from faecal egg counts. It
      has the potential to significantly reduce contamination of pasture with nematode
      eggs. Treated weaners had less dags for 16 weeks and gained more weight than
      untreated weaners.

PMID- 9578767
TI  - Further evidence that zinc sulphate compromises the efficacy of dipping
      treatments using diazinon to control sheep lice (Bovicola ovis).
AB  - OBJECTIVE: To compare the wettability and efficacy of diazinon dip wash made with
      and without the addition of zinc sulphate. DESIGN: Field experiments using a
      shower and a plunge dip complemented by in-vitro wettability experiments.
      PROCEDURE: A flock of infested sheep was divided into groups and treated in a
      shower dip with clear or cloudy dam water plus up to 1.5% zinc sulphate. Another
      infested line of sheep was treated using a plunge dip with nil or 1% zinc
      sulphate. In both experiments, wetting was assessed after dipping and louse
      counts were conducted for 9 months after treatment. Five in-vitro experiments
      compared the wettability of dip wash containing diazinon with up to 1.5% zinc
      sulphate added. RESULTS: In the shower dipping experiment, live lice were found
      at 1 month after dipping in the cloudy water groups with 0.75%, 1.0% and 1.5%
      zinc sulphate and at 2 months in the 0.75% zinc sulphate group. No lice were
      found at subsequent inspections or at any time in the groups that were plunge
      dipped. Zinc sulphate decreased the amount of dip wash retained by wool staples
      in all in-vitro experiments (P < 0.05). CONCLUSION: Zinc sulphate should be
      considered as a risk factor that could cause failure to eradicate a lice
      infestation. The risk can be overcome by ensuring that all sheep are saturated at
      dipping and that the dip wash, and any holding tanks, are agitated throughout the
      dipping event.

PMID- 9578768
TI  - Evaluation of the gamma-interferon assay for eradication of tuberculosis in a
      goat herd.
AB  - OBJECTIVE: To evaluate the usefulness of the gamma-interferon assay in the
      diagnosis of caprine tuberculosis in comparison with a single intradermal
      tuberculin test, and to obtain a group of animals free from this infection in a
      herd with a high prevalence. DESIGN: An immunological study involving four serial
      comparative gamma-interferon and single intradermal tuberculin tests. ANIMALS: A
      herd of 87 goats of Guadarrama breed. PROCEDURE: Serial testing and segregation
      of animals. RESULTS: We found that the number of infections detected by the gamma
      interferon test was considerably greater than the number detected by the single
      intradermal tuberculin test. A group of 10 animals was negative to both tests in
      two consecutive rounds and three kids were negative in the last round of testing.
      CONCLUSIONS: Gamma-interferon assay is appropriate for diagnosis and eradication
      of tuberculosis in goats. This test is able to detect early Mycobacterium bovis
      infection. Avian reactors with simultaneous increased reaction to bovine PPD in
      the gamma-interferon assay (designated as avian reactors) should be considered
      test positive for M bovis. By serial testing with the gamma-interferon and the
      single intradermal tuberculin tests, and a policy of segregation of kids at
      birth, it is possible to achieve a group of animals test negative for
      tuberculosis from a herd of goats with high immunoreactivity to this infection.

PMID- 9578769
TI  - Rate of decline of chlorfluazuron concentration in the fat of cattle.
AB  - OBJECTIVE: To determine the rate of decline of chlorfluazuron (CFZ) concentration
      in the fat of cattle. DESIGN: A field depletion study. ANIMALS: Fifteen steers
      that had become contaminated with CFZ through eating cotton trash or cotton leaf
      pellets derived from CFZ-treated cotton crops. PROCEDURE: Fat samples were
      collected from the cattle at about 3 week intervals according to a schedule where
      each animal was sampled on four occasions up to 340 days after removal from the
      contaminated feed source. RESULTS: When the effects of dilution are removed CFZ
      concentrations were found to decline slowly for about 200 days. Depletion was
      minimal between 200 and 340 days. CONCLUSION: According to this trial, CFZ
      contaminated, nonlactating cattle which have finished growing will remain
      contaminated. Field experience has not supported this conclusion.

PMID- 9578770
TI  - Relationships between vaccine and virulent strains of Babesia bovis during co
      infection in calves.

PMID- 9578771
TI  - Nodules caused by demodex-like mites in the skin of tiger quolls (Dasyurus
      maculatus).

PMID- 9578773
TI  - Mind games.

PMID- 9578772
TI  - Penguin mystery.

PMID- 9578775
TI  - Prevalence of megabacteria in budgerigar colonies.
AB  - OBJECTIVE: To measure the prevalence of megabacteria in budgerigar-breeding
      colonies and to evaluate possible methods to reduce the prevalence. DESIGN: A
      monitoring study over several years. SAMPLE POPULATION: Two budgerigar
      (Melopsittacus undulatus) colonies with over 300 birds each. PROCEDURE: The
      prevalence of megabacteria in the faeces in two budgerigar breeding colonies,
      colony 1 and 2, was determined by faecal examination of each bird. Following an
      initial survey (1990), most of the birds that were scored 2+ or more were culled
      and a management practice was implemented to discriminate against positive birds.
      Consecutive yearly surveys (1991, 1992) were conducted on the young birds bred in
      these colonies. The prevalence of megabacteria in colony 2 was also evaluated in
      1994 and 1996 after all the birds were treated with amphotericin B administered
      in drinking water. RESULTS: The prevalence of megabacteria in the two colonies
      was significantly (P < 0.001) different. Overall the prevalence of megabacteria
      adjusted for colony differences was significantly higher (P < 0.025) in males
      compared to females. Age was not an influencing factor. After the initial survey,
      the prevalence in the offspring did not significantly (P > 0.05) decrease in the
      following two annual breeding seasons but by inference it did significantly
      decrease after amphotericin B treatment. CONCLUSION: The practice of culling most
      birds with more megabacteria in faeces and discriminating against positive birds
      when selecting birds for breeding or culling birds on show quality does not
      decrease megabacteria prevalence in the offspring. However, a reduction in
      prevalence does occur with administration of amphotericin B. Birds may have
      amphotericin B-resistant organisms and these birds need to be identified and
      culled.

PMID- 9578776
TI  - Dentigerous cysts in a Tasmanian sheep flock.

PMID- 9578777
TI  - Inclusion body disease in two captive Australian pythons (Morelia spilota
      variegata and Morelia spilota spilota).
AB  - Two captive Australian pythons, one carpet and one diamond python, presented with
      signs of central nervous system dysfunction. The carpet python was agitated. Its
      head was tilting and it was incoordinated and had convulsions. It was treated
      with antibiotics and anthelmintics but was eventually euthanased after failing to
      respond to therapy. The diamond python had flaccid paralysis of the caudal half.
      It was not treated and became disoriented and died. Hepatocytes from both pythons
      contained irregular 2 to 10 micron eosinophilic intracytoplasmic inclusion
      bodies. The brain of the diamond python was not available for examination.
      Occasional neurones in the carpet python brain contained similar inclusion bodies
      and other changes suggestive of viral infection. The clinical signs and
      histopathological findings in both pythons were consistent with boid inclusion
      body disease.

PMID- 9578778
TI  - Mitotane (o,p'-DDD) resistance in a dog with pituitary-dependent
      hyperadrenocorticism and phaeochromocytoma.
AB  - A dog was presented with a 2 year history of polyuria and polydipsia due to
      pituitary-dependent hyperadrenocorticism. A low-dose dexamethasone suppression
      test and measurement of plasma ACTH concentration confirmed the diagnosis.
      Treatment was instituted with mitotane at 44 mg/kg/day and then 88 mg/kg/d
      without complete resolution of signs. The dog collapsed with signs consistent
      with liver disease and was euthanased. Necropsy revealed a phaeochromocytoma of
      the left adrenal medulla with extensive metastases to the liver. A chromophobe
      adenoma of the pars intermedia of the pituitary was found.

PMID- 9578779
TI  - Exocrine pancreatic insufficiency in a cat.

PMID- 9578780
TI  - Praziquantel in turtles.

PMID- 9578781
TI  - Factors on farms in eastern Australia associated with the development of
      tibiotarsal rotation in ostrich chicks.
AB  - OBJECTIVES: To determine the incidence of tibiotarsal rotation (TTR) in ostrich
      chicks and to identify factors on farms associated with the development of TTR.
      DESIGN: A cross-sectional study using a personal interview. PROCEDURE: During a
      single visit to 31 farms, data were collected about a defined cohort of chicks,
      and about farm-related factors that may be associated with the development of
      TTR. Farms were categorised for TTR status according to the proportion of the
      chick cohort that survived to 10 weeks of age without developing TTR. Chick
      performance was measured using descriptive epidemiological methods and
      univariable analyses were conducted to identify unconditional associations
      between TTR status and farm-related factors. RESULTS: Ninety-six of 931 ostrich
      chicks from 21 (68%) farms developed TTR during the first 10 weeks following
      hatch. Lower limb deformities were the most common cause of death in chicks
      between 3 and 10 weeks of age. On seven (23%) study farms, where less than 87% of
      young chicks survived to 10 weeks without developing this condition, TTR was
      considered a serious problem. Twelve farm-related factors were associated with
      farm TTR status, including eight chick-related variables (aspects of nutrition,
      pen design and management) and four farm-related variables (related to the number
      of veterinary visits, farm location, number of rainy days and the person most
      closely involved with chick raising. CONCLUSION: The results confirm a continuing
      problem of young chick wastage in eastern Australia. TTR was an important cause
      of mortality in farmed ostrich chicks during the first 10 weeks after hatch. The
      factors that producers could address to reduce the incidence of TTR include pen
      design, access to water and nutrition.

PMID- 9578783
TI  - Acute cortisol responses of calves to four methods of dehorning by amputation.
AB  - OBJECTIVE: To measure the plasma cortisol response in calves dehorned by four
      different methods (scoop, guillotine shears, saw, embryotomy wire) for 9 h after
      dehorning. DESIGN: A physiological study with controls. PROCEDURE: Horn
      amputation was carried out on calves restrained manually in a race. RESULTS: The
      four methods of dehorning provoked similarly increased cortisol responses which
      lasted for 6 h. During the first hour after dehorning the plasma cortisol
      concentrations were similar to those following ACTH injection. The overall
      cortisol response to control handling was about 30% of the responses to
      dehorning. CONCLUSIONS: The similarity of the cortisol responses produced by the
      four methods of dehorning suggests that the distress experienced by calves
      following dehorning by amputation is similar regardless of method used.

PMID- 9578782
TI  - Acute cortisol responses of calves to scoop dehorning using local anaesthesia
      and/or cautery of the wound.
AB  - OBJECTIVE: To measure plasma cortisol responses in calves dehorned using a scoop
      after administration of local anaesthesia and/or cautery of the wounds. DESIGN: A
      physiological study with controls. PROCEDURE: There were six treatments: control
      handling with and without local anaesthesia, dehorning, dehorning after local
      anaesthesia, dehorning followed by wound cautery, and dehorning after local
      anaesthesia followed by wound cautery. Blood samples were taken before and after
      dehorning. RESULTS: Dehorning caused an increase in plasma cortisol
      concentrations, which decreased a little to plateau values and then declined to
      pretreatment values 3 to 4 h after dehorning. The peak was smaller after local
      anaesthesia was administered but when its effects wore off, cortisol
      concentrations increased and thereafter were similar to those in the dehorned
      animals. The combination of local anaesthesia and cautery resulted in a plasma
      cortisol response similar to those in control calves with or without local
      anaesthesia. CONCLUSIONS: If plasma cortisol concentrations reflect the distress
      being experienced by the calves, then local anaesthesia reduces the acute
      distress for about 3 h after dehorning but not during the subsequent 3 to 4 h.
      Combining local anaesthetic and cautery prevented the significant increase in
      plasma cortisol following dehorning and may eliminate the acute distress caused
      by scoop dehorning.

PMID- 9578784
TI  - Ameloblastoma in a Merino sheep.

PMID- 9578785
TI  - Occurrence of polychlorinated biphenyls and organochlorine pesticides in
      platypuses (Ornithorhynchus anatinus) in Tasmania.

PMID- 9578786
TI  - Surgical management of flexure deformity of the distal inter-phalangeal joint in
      three Chapman's zebras (Equus burchelli antiquorum).

PMID- 9578788
TI  - Long-term antibody persistence after booster vaccination with combined
      tetravalent diphtheria tetanus, whole-cell Bordetella pertussis and hepatitis B
      vaccine in healthy infants.
AB  - Combining HB vaccine with routine paediatric vaccines has been recognized as the
      best means of universal vaccination against hepatitis B. Our objective was to
      evaluate the long-term antibody persistence of such a combined vaccine in an area
      of high hepatitis B endemicity. We have shown that a DTPw-HB vaccine was safe and
      immunogenic when given as a booster dose at 18 months of age. One month after the
      booster dose of DTPw-HB vaccine, at least 97.8% of subjects had seroprotective
      anti-HBsAg levels, and 1 year later at least 93.9% of these subjects remained
      seroprotected against HBsAg. Immune responses to the DTPw components were similar
      or greater than those of the commercial DTPw vaccine given to the control group.
      This DTPw-HB vaccine, which showed good long-term anti-HBsAg antibody
      persistence, could advantageously replace separate DTPw and HB vaccines in areas
      of high hepatitis B endemicity in terms of clinical, economic and strategic
      benefits.

PMID- 9578789
TI  - Tracheobronchial foreign bodies: a review of children admitted for bronchoscopy
      at King Fahd Specialist Hospital, Al Gassim, Saudi Arabia.
AB  - This is a review of 147 patients suspected of foreign body (FB) inhalation,
      admitted to King Fahd Specialist Hospital in Al Gassim, Saudi Arabia from July
      1989 to December 1994. Age, sex, foreign body type and site, presenting symptoms
      and signs, radiological findings, diagnosis and complications are analyzed and
      discussed. All foreign bodies were removed by rigid bronchoscopy under general
      anaesthesia. The study highlights the magnitude of the problem in the region and
      reviews the clinical presentation of patients who have inhaled an FB and
      recommends bronchoscopy as a means of early diagnosis and management.

PMID- 9578790
TI  - Bacterial isolates from blood and lung aspirate cultures in Gambian children with
      lobar pneumonia.
AB  - As part of a study of the aetiology of pneumonia in malnourished and well
      nourished children, 100 children aged between 3 and 58 months with pneumonia were
      investigated using blood culture and culture of lung or pleural aspirates. In 44
      children one species of bacterium was isolated from blood (6), lung culture (30),
      or both (8), while in eight children two species were isolated. In four of these
      eight children, one organism was isolated from blood culture, while a different
      organism was isolated from lung or pleural aspirate, indicating that blood
      culture does not always reflect the true aetiology of pneumonia. In this group of
      children with lobar pneumonia or empyema, blood culture alone yielded a bacterial
      pathogen in 18 (18%) cases, while the addition of percutaneous lung aspiration or
      pleural aspiration increased the yield to 52 (52%). In experienced hands the
      procedure of percutaneous lung aspiration is safe. It gave significant
      therapeutic advantages to the six children in this series from whom
      Staphylococcus aureus or Mycobacterium tuberculosis were isolated.

PMID- 9578791
TI  - Clinical characteristics and outcome of children aged under 5 years hospitalized
      with severe pneumonia in Yemen.
AB  - A 1-year study of 529 Yemeni children under 5 years of age hospitalized for
      severe pneumonia was undertaken to define their clinical characteristics and to
      identify risk factors associated with death from pneumonia. There were 354
      (66.9%) boys, 270 of the 529 (51%) were under 6 months of age and 457 (86.4%)
      were aged < or = 12 months. The clinical characteristics of the group were as
      follows. Boys constituted 70% of the group and under-1-year-olds 86%, weight-for
      age was under 60% in 23%, clinical rickets was present in 50% and anaemia in 30%
      (30.1%). On admission, cyanosis was detected in 56%, heart failure in 21% and
      isolated hepatomegaly in 14%. Fifty-two children died (CFR 9.8%), of whom 25
      (48%) were under 6 months of age and 20 (38.5%) were aged between 6 and 12
      months. Only seven children aged over 1 year died from pneumonia. Weight-for-age
      less than 60%, rickets, haemoglobin < 10 g/dl, cyanosis and heart failure were
      associated with an increased risk of dying from severe pneumonia.

PMID- 9578792
TI  - Childhood non-traumatic coma in Kuala Lumpur, Malaysia.
AB  - All post-neonatal children with acute non-traumatic coma admitted over an 8-month
      period were analysed and followed up for 18-24 months to determine the aetiology
      and outcome of their coma. One hundred and sixteen children, 72 boys and 44
      girls, were recruited. Half the children were under 1 year of age and only 16
      (14%) were more than 6 years of age. Eighty cases (69%) were due to infection, 15
      (13%) to toxic metabolic causes, six (5%) to hypoxic ischaemic insults, four
      (3.5%) had intracranial haemorrhage, nine (7.8%) were due to miscellaneous causes
      and in two (1.7%) the cause was unknown. Seven cases were lost to follow-up. Of
      the remainder, 39 (35.7%) died, 32 (29.3%) developed permanent neurological
      deficit, and 38 (35%) were discharged well. The outcome was worst in the
      infectious group. Age of onset and sex did not significantly affect outcome. Our
      findings are similar to experience in Japan, where infection accounts for 74% of
      non-traumatic coma, but differ considerably from Western data on childhood coma
      where only a third of cases are due to infection.

PMID- 9578794
TI  - Ultrasound as a screening study for gastro-oesophageal reflux in children.
AB  - A comparison of the abilities of ultrasound and scintigraphy to detect gastro
      oesophageal reflux was made in 110 children (mean age 24.5 months) who were
      divided into groups A (n = 49) and B (n = 61). The former had scintigraphy first
      followed by ultrasound within about 30 min. For group B scintigraphy was also
      performed first, but the delay before ultrasound ranged between 1 and 30 days. In
      most patients (91/110) concordant results were obtained by the two modalities.
      The 19/110 discordant results can be explained by several plausible mechanisms.
      It is concluded that ultrasound should be employed much more frequently as an
      initial investigation when pathological reflux is suspected in children.

PMID- 9578793
TI  - Gestational age assessment by nurses in a developing country using the Ballard
      method, external criteria only.
AB  - The aim of this study was to evaluate postnatal examination of the newborn by
      nurses in a developing country, using a modified Ballard method, scoring for the
      six external criteria only (Ballard-ext). Applicability of gestational age
      estimates with the Ballard-ext. was assessed by calculating its agreement with
      gestational age derived from the last menstrual period (LMP), fundal height and
      the Dubowitz method. The smallest difference in gestational age and the most
      narrow limits of agreement were found between the Ballard-ext. and the Dubowitz
      method. No reliable gestational age could be obtained from LMP or fundal height.
      At low gestational ages, Ballard-ext. tended to give lower gestational ages
      compared with the Dubowitz method. At an average gestational age of more than 251
      days, Ballard-ext. gave higher values compared with Dubowitz. Both Ballard-ext.
      and the Dubowitz method identified 48% of low birthweight babies as growth
      retarded (gestational age > or = 37 weeks). No significant difference in
      gestational age assessment of newborns between nurses was observed. The Ballard
      method, scoring for external criteria alone, compared favourably with the
      Dubowitz method. The test is simple to perform and can be reliably used routinely
      by nurses.

PMID- 9578795
TI  - Eye protection for newborns under phototherapy: comparison between a modified
      headbox and the conventional eyepatches.
AB  - In a randomized trial comparing a modified oxygen headbox with conventional eye
      patches for protecting the eyes of newborn infants undergoing phototherapy, the
      use of the headbox did not interfere with phototherapy treatment and was
      preferred by the nursing staff, as shown by an opinion survey. This, plus our
      previously reported finding that the headbox was associated with less eye
      infection, less periorbital skin irritation and less accidental exposure of the
      eyes due to displacement of the protective devices, suggests that the headbox
      provides a convenient and inexpensive alternative method of eye protection. The
      device may be particularly useful in busy and under-staffed neonatal units where
      vigilant eye care of infants undergoing phototherapy may be difficult.

PMID- 9578796
TI  - Predictors of mortality in Gambian children with severe malaria anaemia.
AB  - Severe malaria anaemia is a frequent cause of admission to hospital in tropical
      Africa and about 10% of children with this condition die. To determine ways in
      which mortality might be reduced we have studied risk factors for a fatal outcome
      in 173 children with severe malaria anaemia who were assigned to receive blood
      transfusion because they had a packed cell volume of less than 12% and/or signs
      of respiratory distress. Twenty-three children died (13%); in 15 cases (65%)
      death occurred before blood transfusion was given. The presence of respiratory
      distress was found to be the most important predictor of death. Children with
      severe malaria anaemia and signs of respiratory distress must therefore be
      transfused as soon as possible.

PMID- 9578797
TI  - Diarrhoea mortality in Aracaju, Brazil.
AB  - We report diarrhoea mortality rates in the city of Aracaju, Brazil from 1992 to
      1994 when there were 318 deaths due to diarrhoea. Eighty-nine per cent of deaths
      occurred in infants: 53.1% were boys and 78.9% died in hospital. Diarrhoea
      mortality rates for children under 5 years of age were 2.63, 1.78 and 1.28 for
      1992, 1993 and 1994, respectively. The district with the most slums and least
      sewerage services had the highest mortality rates (4.29, 2.53 and 1.87 for 1992,
      1993 and 1994, respectively) and the district with most services and fewest slums
      had the lowest rates each year (0.79, 0.55 and 0.38). Malnutrition was associated
      with diarrhoea on 26.5% of death certificates. Mortality rates fell during the
      study period but still remained high in infants from poor areas of the city.
      Study of the geographical distribution of mortality allowed identification of
      priority areas for targeted interventions.

PMID- 9578798
TI  - Hodgkin's disease in children in southern Africa: epidemiological
      characteristics, morbidity and long-term outcome.
AB  - We reviewed 39 children < 15 years of age treated for Hodgkin's disease (HD) from
      1973 to 1996. There were seven black, 12 white and 20 coloured children (of mixed
      ethnic origin). The M:F ratio was 2.9:1 and the median ages 147, 124 and 119
      months in white, coloured and black children, respectively. Coloured and black
      children came mainly from a poor socio-economic background. Cervical
      lymphadenopathy was present in 74% and systemic symptoms in 51% of cases. Five
      per cent had clinical stage I, 41% stage II, 28% stage III and 26% stage IV
      disease. Two children underwent a staging splenectomy. The majority of white
      children presented with stages I and II and the majority of black and coloured
      children with stages III and IV HD. Nodular sclerosing (59%), mixed cellularity
      (40%) and lymphocyte-depleted (43%) were the most common histological subtypes in
      white, coloured and black children, respectively. Epidemiologically, white
      children fitted the criteria for HD type I and coloured and black children the
      criteria for HD type III. Nineteen children were treated with ChlVPP
      (chlorambucil, vinblastine, prednisone, procarbazine) and 20 with MOPP (mustine,
      Oncovin, procarbazine, prednisone) and/or ABVD (Adriamycin, bleomycin,
      vinblastine, DTIC) with involved field radiotherapy to bulky mediastinal disease.
      The projected 10-year survival after ChlVPP or MOPP/ABVD therapy was similar at
      52%. In stages I and II, HD projected survival at 5 and 10 years was 85%, and in
      stages III and IV it was 82% at 5 and 48% at 10 years. The relapse rate was 47%
      in stage II, 45% in stage III and 44% in stage IV. Tuberculosis was suspected and
      treated in five children at the time of, and in seven children (three confirmed)
      subsequent to, the diagnosis of HD. Varicella developed in six and herpes zoster
      in five children. Five treatment-related deaths were due to septicaemia following
      splenectomy (two), marrow failure, corpulmonale and secondary leukaemia.

PMID- 9578799
TI  - Familial Burkitt's lymphoma in Nigerians.
AB  - Three Nigerian sib-pairs with familial Burkitt's lymphoma (BL) seen between 1986
      and 1996 are described. Their ages ranged from 4 to 20 years (median 9.5), and
      there were five males and one female. The mean age interval between each pair at
      presentation was 4 years (3-6) and the mean time interval 22 months (0.3-41). Two
      of the sib-pairs were sex-concordant, including a set of monozygotic twins. Five
      of the patients presented in stage C and one in stage A. Parental consanguinity
      was not found in any group. Space-clustering was confirmed in all three but time
      clustering in only one. The occurrence of BL in multiple members of the same
      family, the presence of sex concordance and the relatively wide variation in the
      time of onset of disease between each pair suggest genetic predisposition as a
      possible additional aetiological factor for BL in the families affected.

PMID- 9578800
TI  - Group A beta-haemolytic streptococcal infection and Henoch-Schonlein purpura with
      cardiac, renal and neurological complications.
AB  - A 6-year-old girl had a group A beta-haemolytic streptococcal (GABS) throat
      infection and Henoch-Schonlein purpura (HSP). The clinical course was complicated
      by nephrotic syndrome due to crescentic glomerulonephritis, transient
      neurological symptoms due to focal ischaemia of the brain, and congestive cardiac
      failure due to myocarditis. The clinical presentation highlights the diversity of
      systemic involvement in HSP, the transient nature of apparently serious central
      nervous system involvement, and a possible role of GABS in its aetiology.

PMID- 9578801
TI  - The utilization of a paediatric emergency room in a general hospital in Kuwait.
AB  - A descriptive study was conducted in Al-Amiri Hospital, Kuwait to evaluate the
      use of the paediatric emergency room (PER) by children under 12 years of age over
      an 11-week period. Socio-demographic data on the families, reasons for the
      visits, the pattern of referral and the diagnoses were reviewed and analyzed. A
      total of 277 children were enrolled in the study, the majority of whom (81%) were
      generally well, only 4% requiring admission to hospital. The paediatrician in the
      emergency room considered that 64% of visits were not emergencies. Some form of
      treatment and one to two routine investigations were needed in 21% and 21.6%,
      respectively. Stated reasons for seeking medical care were: symptoms of the child
      (34%), unavailability of primary clinic at night (22%) and perceived better
      services in hospital (20%). The median of parental satisfaction at the end of the
      visit was 95%. We conclude that most visits to the PER at Al-Amiri Hospital are
      inappropriate and that intensive health education is required to improve use of
      the PER and to increase public awareness of the difference between primary care
      and paediatric emergency facilities.

PMID- 9578802
TI  - Force acting on spheres adhered to a vessel wall.
AB  - To evaluate the force and torque acting on leukocytes attached to the vessel
      wall, we numerically study the flow field around the leukocytes by using rigid
      spherical particles adhered to the wall of a circular cylindrical tube as a model
      of adherent leukocytes. The adherent particles are assumed to be placed regularly
      in the flow direction with equal spacings, in one row or two rows. The flow field
      of the suspending fluid is analyzed by a finite element method applied to the
      Stokes equations, and the drag force and torque acting on each particle, as well
      as the apparent viscosity, are evaluated as a function of the particle to tube
      diameter ratio and the particle arrangements. For two-row arrangements of adhered
      particles where neighboring particles are placed alternately on opposite sides of
      the vessel, the drag and the torque exerted on each particle are higher than
      those for single-row arrangements, for constant particle to tube diameter ratio
      and axial spacing between neighboring particles. This is enhanced for larger
      particles and smaller axial spacings. The apparent viscosity of the flow through
      vessels with adhered particles is found to be significantly higher than that
      without adhered particles or when the particles are freely floating through the
      vessels.

PMID- 9578803
TI  - Computer simulation of concentrated fluid-particle suspension flows in
      axisymmetric geometries.
AB  - To investigate the particle migration effects and fluid-particle interaction
      occurring in the flow of highly concentrated fluid-particle suspensions, a
      numerical method has been developed for effective computer simulation in
      arbitrary axisymmetric geometries. In the mathematical flow model the suspension
      is treated as a generalized Newtonian fluid where the effective flow properties
      of the suspension (density and viscosity) are determined by the local volume
      fraction of the particles. The description of the particle motion is governed by
      a modified transport equation with diffusion coefficients accounting for the
      effects of shear-induced particle migrations. The strongly coupled system of flow
      and transport equations is solved by applying the Galerkin finite element method
      and a velocity-pressure projection scheme. The numerical results in tube flow
      demonstrate strong particle migration towards the center of the tube and an
      increasing blunting of the velocity profiles which is in good agreement with an
      available analytical solution. In the case of flow through a stenosed tube model,
      particle concentration is lowest at the site of maximum constriction whereas a
      strong accumulation of particles can be seen in the recirculation zone downstream
      of the stenosis.

PMID- 9578804
TI  - Biorheological features of some soft tissues under a surgical tissue expansion
      procedure.
AB  - The aim of this study was to investigate the effects of a surgical tissue
      expansion procedure on the biomechanical features of the expanded soft tissues.
      In this procedure a silicone balloon "expander" is surgically inserted into a
      tissue and inflated. The tissue mass increases under the stretch of the expander.
      The increased tissue can then be used as an autologous source for the surgical
      reconstruction of organs. In this article, dog saphenous neurovascular bundle was
      used. Expanded saphenous nerves, arteries and veins were harvested and their
      biomechanical features and ultrastructural, histological changes were studied.
      The stress relaxation features, the continuous spectrum of relaxation time, and
      the stress-strain relationship of expanded and control specimens were measured.
      Results show that within two or three weeks after placement of the expanders, the
      biomechanical properties of expanded saphenous nerves, arteries and veins began
      to deviate from those of their controls, and the differences between them were
      proportional to the volume of inflation; but when the expanding period was 15
      weeks or longer, the properties of expanded specimens and their controls became
      close again. Histological study showed that the content of collagenous fibers in
      blood vessel walls decreased after expansion. The content of elastic fibers in
      blood vessel walls first increased, then returned to normal, and finally
      decreased. Ultrastructural studies showed that when elongated by 25-40%, the
      expanded nerves had well preserved axons and showed fewer smooth myelin sheaths
      only in the middle and distal part of the expansion.

PMID- 9578806
TI  - Comparison of the mechanical properties of normal and transformed fibroblasts.
AB  - In order to achieve coordinated migration through extracellular matrix and
      endothelial barriers during metastasis, cancer cells must be endowed with
      specific structural and adhesive properties. In this context, comparison of the
      mechanical properties of transformed versus normal cells, on which little
      quantitative information is available, was the focus of this study. Normal human
      dermal fibroblasts and their SV40-transformed counterparts were analyzed using
      various manipulations. First, micropipet aspiration of suspended cells allowed
      calculation of a cortical tension (similar for normal and transformed cells), and
      an apparent viscosity (30% lower for transformed than for normal fibroblasts); in
      addition, transformed fibroblasts exhibited a more fragile surface than their
      normal counterparts. Second, tangential ultracentrifugation of adherent cells
      demonstrated cellular elongation in the direction of the centrifugal field and
      the existence of critical forces for cell detachment, around 10(-7) N: these were
      1.6-fold greater for normal than for transformed cells. Finally, examination of
      the wrinkle patterns formed by cells plated on a deformable polydimethylsiloxane
      substrate, plus analysis of cell retraction caused by ATP treatment following
      detergent permeabilization showed that normal fibroblasts exhibited much more
      contractility than their transformed counterparts, which we characterized by a
      cell contraction rate. Such quantitative parameters which reveal differences in
      the mechanical behavior of normal and transformed cells may be used in the future
      as new markers of oncogenic transformation.

PMID- 9578805
TI  - Effects of lipid on the structure and rheology of gels formed by canine
      submaxillary mucin.
AB  - Rheological experiments have shown that canine submaxillary mucin (CSM) forms
      gels in aqueous solution at low ionic strength and in 6M GdnHCl. Examination of
      specimens of intact CSM and also its subunits prepared by reduction and
      carboxymethylation showed that the presence of lipid increases the gel-forming
      capability, probably as a result of enhancement of the intermolecular hydrophobic
      interactions. The rheological evidence for gelation is that substantially larger
      values of the oscillatory storage modulus, G' (omega), and the dynamic complex
      viscosity, eta*(omega), are observed for lipid-containing CSM. This is backed up
      by electron micrographs of freeze fractured specimens, where we observe a network
      morphology in which the cross-links are formed as a result of non-bonded
      interactions between a number of CSM chains. The intermolecular interactions
      responsible for gelation probably involve hydrophobic association between the
      interdigitated oligosaccharides, and/or between the non-glycosylated regions of
      the protein core, and can occur even in a highly chaotropic medium (6M GdnHCl).
      In contrast to previous experiments with porcine submaxillary mucin and human
      tracheobronchial mucin, which form microphase-separated gels in aqueous solution,
      CSM solutions undergo macroscopic phase separation into polymerrich (gel) and
      polymer-poor (sol) phases. These data point to stronger hydrophobic interactions
      in lipid-containing CSM.

PMID- 9578807
TI  - Spectrin properties and the elasticity of the red blood cell membrane skeleton.
AB  - Two models of spectrin elasticity are developed and compared to experimental
      measurements of the red blood cell (RBC) membrane shear modulus through the use
      of an elastic finite element model of the RBC membrane skeleton. The two
      molecular models of spectrin are: (i) An entropic spring model of spectrin as a
      flexible chain. This is a model proposed by several previous authors. (ii) An
      elastic model of a helical coiled-coil which expands by increasing helical pitch.
      In previous papers, we have computed the relationship between the stiffness of a
      single spectrin molecule (K) and the shear modulus of a network (mu), and have
      shown that this behavior is strongly dependent upon network topology. For
      realistic network models of the RBC membrane skeleton, we equate mu to
      micropipette measurements of RBCs and predict K for spectrin that is consistent
      with the coiled-coli molecular model. The value of spectrin stiffness derived
      from the entropic molecular model would need to be at least 30 times greater to
      match the experimental results. Thus, the conclusion of this study is that a
      helical coiled-coil model for spectrin is more realistic than a purely entropic
      model.

PMID- 9578808
TI  - Determination of particle sedimentation rate by ultrasonic interferometry: role
      of particle size, density and volume fraction.
AB  - The sedimentation rate (SR) of non-aggregated spherical particles in suspension
      was determined using an ultrasonic interferometry technique (Echo-Cell); this
      method is based on A-mode echography and measures the rate of formation of a
      sediment on a solid plate during settling. The particle accumulation rate, which
      is related to SR, is obtained from the interference of two waves reflected by two
      interfaces: one between the plate and the sediment and the other between the
      sediment and the suspension. Studies were carried out at 25 degrees C using latex
      spheres of different diameters (7 to 20 micron) and densities (1.062 to 1.190
      g/cm3) suspended in distilled water at various volume fractions (1% to 5%). As
      anticipated by the Stokes model, linear relations were found between SR and both
      particle density and the square of particle radius. Experimental SR values
      decreased with increasing suspension particle concentration; these concentration
      effects were in good agreement with those predicted by the Steinour model. Our
      results thus serve to validate the theoretical aspects of the Echo-Cell method
      and suggest its usefulness as a tool for studies of RBC interaction and RBC
      aggregation.

PMID- 9578809
TI  - A commentary on the "in vivo viscosity law".

PMID- 9578810
TI  - Cellular determinants of low-shear blood viscosity comment.

PMID- 9578811
TI  - ACTH precursors: biological significance and clinical relevance.

PMID- 9578812
TI  - Clinical manifestations of abnormalities of the calcium sensing receptor.

PMID- 9578813
TI  - The development of the foetal thyroid: in utero ultrasonographic measurements.
AB  - OBJECTIVE: The early recognition of potentially treatable thyroid disease in the
      foetus frequently depends on the detection of abnormal growth of the foetal
      thyroid gland. We have therefore established nomograms for foetal thyroid
      transverse width and circumference from 14 weeks of gestation until term, using
      transvaginal and transabdominal high-resolution ultrasound techniques. DESIGN: A
      prospective, cross-sectional study of 193 normal singleton pregnancies was
      performed. MEASUREMENTS: Thyroid size was measured by transvaginal
      ultrasonography between 14 and 17 weeks, and by abdominal ultrasound from 18 to
      37 weeks of gestation. RESULTS: Data was accurately obtained for 193 foetuses.
      The mean +/- SD thyroid width and circumference were 11.7 +/- 4.1 mm (95%
      confidence interval 11.1-12.3) and 39.5 +/- 14.1 mm (95% confidence interval 37.4
      41.6), respectively. Thyroid size as a function of gestational age was expressed
      by the regression equations: thyroid width (mm) = -3.94 + 0.68 x gestational age
      (weeks), and thyroid circumference (mm) = -1.38 + 0.23 x gestational age (weeks).
      The correlation coefficients, r = 0.91 and r = 0.93, for thyroid width and
      circumference, respectively, were found to be highly statistically significant (p
      < 0.0001). The normal mean of thyroid width and circumference for each week of
      gestational age and the 95% prediction limits were defined. CONCLUSIONS: The
      present data offer normative measurements of the foetal thyroid that may
      facilitate the prenatal diagnosis of foetal goitre and make early administration
      of in utero treatment possible.

PMID- 9578814
TI  - Prognostic factors for survival and for biochemical cure in medullary thyroid
      carcinoma: results in 899 patients. The GETC Study Group. Groupe d'etude des
      tumeurs a calcitonine.
AB  - BACKGROUND: Prognostic factors of sporadic or inherited medullary thyroid
      carcinoma (MTC) are still controversial and have been assessed in old and small
      series. A better knowledge of these factors would improve patient management.
      OBJECTIVE: To evaluate factors involved in the prognosis of MTC in a large series
      of cases, using uni- and multivariate analysis. DESIGN AND PATIENTS: Clinical,
      biological, surgical and epidemiological data on 899 MTC patients, diagnosed
      between 1952 and 1996, were collected by the French Calcitonin Tumors Study Group
      (GETC) with a standardized questionnaire, and processed in a national database.
      MEASUREMENTS: Survival and biochemical cure (i.e. normal basal post-operative
      serum calcitonin levels) were analysed with Kaplan and Meier and log-rank test
      statistical procedures. Data are presented as adjusted rather than observed
      survival, to consider only patients who died of MTC. Cox's forward-stepping
      proportional hazard model was used to analyse factors with a significant
      influence on survival by univariate analysis. RESULTS: Apart from the large
      proportion of familial forms (43%), the general characteristics of our population
      were similar to those in other studies: mean age at surgery = 43.4 years; sex
      ratio = 1 male/1.35 female; stage I = 20.8%; stage II = 21.2%; stage III = 46.5%
      and stage IV = 11.5%. 863 (96%) patients underwent surgery; 43% of operated
      patients were biochemically cured. Adjusted survival was 85.7 +/- 1.5% at 5 years
      and 78.4 +/- 2.1% at 10 years. Multivariate analysis showed that age and stage
      were independent predictive factors of survival. Gender, type of surgery, type of
      familial form were predictive only in univariate analysis. Biochemical cure
      predicts a survival rate of 97.7% at 10 years. Authentic recurrence, that is
      subsequent elevation of calcitonin (CT) after post-operative normalization, was
      found in 4.9%. In non-cured patients (57%), survival was still good: 80.2% (+/-
      2.2%) and 70.3% (+/- 2.9%) at 5 and 10 years, respectively. Similarly, prediction
      of biochemical cure was solely dependent on stage. CONCLUSION: Survival of these
      medullary thyroid carcinoma patients appears better than expected even in non
      cured patients. Considering the strong impact of stage, the necessity for pre
      operative diagnosis of MTC is obvious.

PMID- 9578816
TI  - Radioiodine treatment in unsuspected pregnancy.
AB  - OBJECTIVE: Radioiodine is being used increasingly as first line therapy for
      hyperthyroidism. Our aim is to highlight some of the difficulties which can occur
      following the use of 131I to treat hyperthyroidism in fertile women. PATIENTS: We
      present 3 cases of young women to whom radioiodine was given, only to find some
      weeks later that they had been pregnant at the time of treatment. CONCLUSIONS:
      These cases serve as a reminder of the importance of obtaining an accurate and
      full menstrual and contraceptive history. Guidelines advocate the application of
      the ten day rule with the further recommendation that pregnancy testing may be
      undertaken as an alternative.

PMID- 9578815
TI  - Elevated serum granulocyte colony-stimulating factor levels in patients with
      Graves' disease.
AB  - OBJECTIVE: Agranulocytosis is a serious side effect of anti-thyroid drugs (ATD).
      Granulocyte colony-stimulating factor (G-CSF) is one of the cytokines that
      increase granulocyte number. The aim of this study was to examine the sequential
      variation of serum G-CSF levels in patients with Graves' disease before and after
      ATD therapy. PATIENTS: Sixty-three patients with Graves' disease were studied
      before, during and after treatment with methimazole (MMI). Serum samples from 71
      healthy subjects were used as controls. DESIGN AND MEASUREMENTS: Serum levels of
      G-CSF were measured by a novel chemiluminescent enzyme immunoassay, which was
      sensitive enough to determine G-CSF levels in healthy subjects. Blood granulocyte
      counts, serum, thyroid hormone and TSH levels, and titres of thyroid
      autoantibodies were also measured. RESULTS: Serum G-CSF levels in Graves'
      patients before and 2 weeks after MMI were significantly higher than in healthy
      subjects. There was a significant correlation between serum G-CSF levels and
      granulocyte counts in untreated patients with Graves' disease. Untreated patients
      with granulocyte counts less than 2 x 10(9)/I had significantly lower serum G-CSF
      levels as compared with other untreated patients. Serum G-CSF levels gradually
      decreased thereafter. No correlation was observed between serum G-CSF levels and
      serum thyroid hormone levels or titres of thyroid autoantibodies. After ATD
      treatment, no correlation was found between serum G-CSF levels and granulocytes
      counts. There was no significant correlation between the change of serum G-CSF
      levels and that of granulocyte counts before and after MMI treatment. Graves'
      patients with mild agranulocytosis had normal or elevated serum G-CSF levels.
      CONCLUSIONS: Significantly elevated serum G-CSF levels were observed in patients
      with Graves' hyperthyroidism. During ATD therapy, deficiency of G-CSF was not
      identified as a cause of agranulocytosis in this study.

PMID- 9578817
TI  - Normalization of serum thyrotrophin by means of radioiodine treatment in
      subclinical hyperthyroidism: effect on bone loss in postmenopausal women.
AB  - BACKGROUND: Patients with subclinical hyperthyroidism (reduced serum TSH and
      normal free T4 and T3 concentrations) have slightly increased bone turnover and
      might have reduced bone mass, especially among postmenopausal women (due to
      concomitantly reduced oestrogen production), as also seen during suppressive L-T4
      treatment. OBJECTIVE: We have evaluated whether normalization of serum TSH using
      radioiodine treatment (RAI) in postmenopausal women with a nodular goitre and
      subclinical hyperthyroidism, protects against bone loss? DESIGN: Prospective, non
      randomized study, outpatients 2 years follow-up. PATIENTS: Postmenopausal women
      with a nodular goitre, biochemically subclinical hyperthyroidism (TSH < 0.2 mU/I,
      and signs of a growing goitre or compression symptoms. Sixteen were treated with
      RAI (median dose 555 MBq) (+RAI), whereas 12 were followed without treatment (
      RAI). MEASUREMENTS: Serum TSH (third generation technology), free T4 and T3
      indices, and bone mass (BMD) as measured by Dual Photon Absorptiometry (4 in each
      group) (only spine) or Dual X-ray Absorptiometry (DEXA) (both spine and hip),
      were measured yearly for up to 2 years. RESULTS: The two groups did not differ
      regarding age, thyroid hormone parameters, and absolute levels of BMD at spine
      and hip. RAI resulted in normalization of TSH in all 16 women, and FT4I as well
      as FT3I decreased to 78% after one year (P < 0.01). These parameters did not
      change in the untreated group, thus serum TSH remained reduced. BMD at the spine
      tended to increase (n.s.) after RAI to (median) 101.9% after one year, and 101.5%
      after 2 years. In contrast the -RAI group experienced a continued fall in BMD to
      97.3% after one year, and 95.5% after 2 years, both reduced as compared to the
      +RAI group (P < 0.02). BMD of the hip also increased after RAI, to 102.3% after
      one year, and 101.7% after 2 years. In contrast BMD in the -RAI group decreased
      to 94.8% after one year, and 98.0% after 2 years, both lower than in the +RAI
      group (P < 0.01). CONCLUSIONS: Subclinical hyperthyroidism due to a nodular
      goitre in postmenopausal women resulted in a continued loss of bone mass of about
      2% per year. Radioiodine treatment resulting in normalization of serum TSH
      prevented this continued bone loss for at least 2 years. Our study supports
      earlier intervention in such patients.

PMID- 9578819
TI  - Serum leptin concentrations in patients with thyroid disorders.
AB  - OBJECTIVE: Leptin, the obese gene product, is secreted exclusively by adipocytes
      and is thought to act as a lipostatic signal that regulates body weight
      homeostasis. We previously reported that thyroid hormone is one of the up
      regulating factors of leptin in vitro. T3, at physiological concentrations,
      stimulates leptin mRNA expression and leptin secretion by 3T3-L1 adipocytes. The
      aim of this study was to explore the role of thyroid hormone in the regulation of
      leptin in humans. DESIGN AND PATIENTS: A total of 59 non-obese women aged 38.4 +/
      1.8 years (mean +/- SEM) were studied: 19 patients with hyperthyroidism, 17
      patients with hypothyroidism, and 23 normal control subjects. The correlation
      between serum leptin concentrations and body mass index (BMI) was analyzed, and
      serum leptin levels were compared among the three groups. MEASUREMENTS: Serum
      leptin concentrations were measured by radioimmunoassay. RESULTS: Serum leptin
      concentrations after logarithmic transformation were correlated significantly (P
      < 0.05) with BMI in the hyperthyroid (r = 0.46), the hypothyroid (r = 0.84), and
      normal (r = 0.63) groups. Even though age, body weight, and BMI were similar in
      all groups, serum leptin levels in the hypothyroid patients (5.30 +/- 1.12
      micrograms/l) were significantly (P < 0.05) lower than in the hyperthyroid and
      normal groups (6.87 +/- 0.66 and 6.58 +/- 0.68 micrograms/l, respectively).
      CONCLUSIONS: These results indicate that thyroid hormone may play an important
      role in the appropriate secretion of leptin in humans.

PMID- 9578818
TI  - Plasma sex hormones are significantly associated with plasma leptin concentration
      in healthy subjects.
AB  - OBJECTIVE: In humans a sexual dimorphism of plasma leptin concentration has been
      demonstrated but its significance remains to be established. Sex hormones may
      have a role. PATIENTS: Eighty healthy, non-obese subjects (41M/39F) were studied.
      MEASUREMENTS: In the whole group of subjects plasma sex hormones, leptin and
      insulin concentrations were determined, body fat content assessed by bioimpedance
      analysis, body fat distribution evaluated and insulin-mediated glucose uptake
      measured by euglycemic hyperinsulinemic glucose. RESULTS: After adjustment for
      age, gender, amount of body fat, waist/hip ratio (WHR) and fasting plasma insulin
      concentration, fasting plasma leptin was still significantly correlated with
      plasma DHEAS (r = -0.30, P < 0.006), oestradiol (r = 0.53, P < 0.001) and
      testosterone (r = -0.43, P < 0.001) in all subjects (n = 80). Independently of
      age, amount of body fat and WHR, fasting plasma leptin concentration correlated
      with plasma oestradiol (r = 0.38, P < 0.01) and total testosterone (r = -0.58, P
      < 0.001) in males (n = 41) and with fasting plasma oestradiol (r = 0.48, P <
      0.002) in females (n = 39). To investigate the independent contribution of
      anthropometric and hormonal variables to fasting plasma leptin concentration, a
      multivariate stepwise regression analysis with fasting plasma leptin
      concentration as dependent variable was made. In the entire group (n = 80), the
      whole model explained 43% of fasting plasma leptin concentration with fasting
      plasma insulin, total testosterone and oestradiol concentrations significantly
      and independently associated with plasma leptin concentration. In this model,
      fasting plasma DHEAS, testosterone and oestradiol explained 25% of the
      variability in plasma leptin concentration. CONCLUSION: Our study demonstrates
      that plasma sex hormone concentrations are associated with plasma leptin
      concentration.

PMID- 9578821
TI  - Long-term therapy with long-acting octreotide (Sandostatin-LAR) for the
      management of acromegaly.
AB  - OBJECTIVES: To evaluate the efficacy and safety of a long-acting preparation of
      the somatostatin analogue octreotide, Sandostatin-LAR (SMS-LAR) for the treatment
      of acromegaly. DESIGN AND PATIENTS: Thirteen patients with acromegaly received
      intramuscular injections of SMS-LAR 20-40 mg at 4-6 week intervals for a period
      of up to 3 years. MEASUREMENTS: Serial measurement of serum GH and IGF
      concentrations were obtained. Symptoms related to acromegaly were scored by
      patients at baseline and following each injection. Serial gallbladder ultrasound
      and pituitary imaging was performed throughout the study. RESULTS: One patient
      was withdrawn from the study after 6 months because of continued gastrointestinal
      side effects; 4 patients were treated with monthly injections for 12 months and 8
      patients with injections at either 1 month or 6-week intervals for 36 months;
      hence data is presented for n = 12 for up to 12 months; and thereafter n = 8. SMS
      LAR significantly reduced serum GH and IGF-1 values: for the whole group GH
      concentrations fell from 24.8 +/- 4.2 mU/l (mean +/- SE) at baseline to 5.2 +/-
      0.8 mU/l at 12 months (P < 0.01, n = 12). In the 8 patients treated for 3 years
      GH fell from 27.8 +/- 6.1 mU/l at baseline to 4.2 +/- 0.8 mU/l at the end of 3
      years (P < 0.01, n = 8). GH fell to < 10 mU/l in all subjects and was < 5 mU/l in
      50% after both 1 and 3 years. IGF-1 concentrations fell from 95 +/- 13 nmol/l at
      baseline to 63 +/- 13 nmol/l after 1 year (P < 0.01, n = 12; reference range < 65
      nmol/l). In the 8 patients treated for 3 years IGF-1 concentrations fell from 119
      +/- 14 nmol/l at baseline to 60 +/- 13 nmol/l after 3 years (P < 0.001, n = 8).
      IGF-1 was < 65 nmol/l in 60% of patients after 1 year and 75% after 3 years.
      Treatment resulted in trends towards improvement in symptoms of acromegaly and
      statistically significant improvement in sweating. There was no evidence of
      tachyphylaxis or evidence to suggest development of glucose intolerance. Only 2
      patients (15%) developed gallbladder sludge which was asymptomatic; no patient
      developed gallstones. CONCLUSIONS: We conclude that SMS-LAR is a safe, effective
      and well tolerated treatment, making it an important therapeutic option in the
      management of acromegaly.

PMID- 9578820
TI  - The octreotide suppression test and [111In-DTPA-D-Phe1]-octreotide scintigraphy
      in neuroendocrine tumours correlate with responsiveness to somatostatin analogue
      treatment.
AB  - OBJECTIVE: The somatostatin analogue octreotide (Sandostatin, Novartis, Basie)
      significantly improves the syndromes suffered by most patients with
      neuroendocrine tumours (NETs). The use of [111In-DTPA-D-Phe1]-octreotide
      scintigraphy ([111In]-pentetreotide) to predict the response to octreotide
      treatment has been described. Short-term hormone inhibition by a single injection
      of octreotide has also been reported. This study aimed to compare the effects of
      the suppression test with the response to long-term somatostatin analogue
      treatment, and to seek a correlation between the short-term suppression test,
      [11In]-pentetreotide observations and long-term somatostatin analogue treatment.
      DESIGN AND MEASUREMENTS: Short octreotide suppression test and octreotide
      scintigraphy. Blood samples were collected before (0900, 0930 h), at (1000 h),
      and after (1030, 1100, 1200, 1300 h) the injection of 50 micrograms octreotide
      subcutaneously. Plasma hormones relevant to the syndrome were analysed by
      radioimmunoassay. The short suppression effects, the [111In]-pentetreotide
      observations and the response to long-term treatment with somatostatin analogue
      were evaluated and compared. PATIENTS: Twenty-six patients with metastatic NETs
      were evaluated, including 14 carcinoid tumours, 10 pancreatic endocrine tumours
      and 2 medullary carcinomas of thyroid (MCTs). Twelve patients had received
      octreotide treatment before the study, another 4 patients were treated
      subsequently with somatostatin analogue. RESULTS: During the short suppression
      test, hormones relevant to the syndromes were suppressed in 24 patients (those
      with carcinoids and pancreatic endocrine tumours). There was no suppression in
      the 2 patients with MCT. [111In]-pentetreotide observations closely correlated
      with the short suppression response to octreotide. Fourteen patients were treated
      with somatostatin analogue, and responded clinically; they had a positive short
      inhibition test and positive tumour uptake. Two patients with MCT did not respond
      to the treatment and had a negative suppression test and a negative [111In]
      pentetreotide. CONCLUSION: Our results suggest that a consistent relationship
      exists between the short suppression test and the response to somatostatin
      analogue treatment in the majority of the patients with neuroendocrine tumours.
      The octreotide suppression test and octreotide scintigraphy together will be
      helpful in selecting appropriate patients for clinical treatment with
      somatostatin analogues.

PMID- 9578822
TI  - Urinary glycosylated, free and total pyridinoline and free and total
      deoxypyridinoline in diabetes mellitus.
AB  - OBJECTIVE: Published data on bone metabolism in diabetes mellitus are
      conflicting. We have measured pyridinium crosslinks, biochemical markers of bone
      resorption, in order to evaluate bone resorption in diabetes mellitus. We also
      wished to investigate whether, as a consequence of chronic hyperglycaemia,
      pyridinoline is glycosylated to a greater extent in patients with diabetes
      mellitus. DESIGN AND PATIENTS: This cross sectional study included 142 patients
      (64 males, 78 females) with insulin dependent and non-insulin dependent diabetes
      mellitus (IDDM and NIDDM). These patients were compared to a healthy control
      group of 99 individuals (39 males and 60 females). MEASUREMENTS: Pyridinium
      crosslinks, glycosylated, free and total pyridinoline (gPYD, fPYD, tPYD) and free
      and total deoxypridinoline (fDPD, tDPD) were measured in a spot urine sample by
      high performance liquid chromatography (HPLC). Urinary creatinine, albumin and
      glucose were also measured. RESULTS: In the diabetic group, values of urinary
      gPYD and tDYD were significantly lower than in controls. gPYD excretion was
      lowest in patients with severe glycosuria. Free pyridinium crosslinks, both fPYD
      and fDPD, were excreted to a significantly lower extent. The molar ratio of tPYD
      to tDPD was significantly increased in diabetes mellitus. CONCLUSIONS: Decreased
      excretion of tDPD suggests low bone resorption in IDDM and NIDDM. Pyridinoline is
      not glycosylated to a greater extent in diabetes mellitus and tends to be
      decreased in proportion to the degree of glycosuria. Excretion of gPYD, fPYD and
      fDPD is depressed in severe glycosuria. Diminshed degradation to the final
      products, fPYD and fDPD, might represent increased resistance to enzymatic
      activity or diminished enzymatic activity. The increased molar ratio tPYD/tDPD in
      urine suggests an increased ratio in bone collagen in diabetes mellitus.

PMID- 9578823
TI  - Aromatase in the human central nervous system.
AB  - OBJECTIVE: Oestrogen produced locally by aromatase is thought to participate in
      numerous biological functions in the adult central nervous system (CNS). However,
      little is known about aromatase expression in the human CNS. DESIGN: We examined
      aromatase expression in human brain regions, (4 men, 2 women) obtained from
      autopsy, by reverse transcriptase (RT)-polymerase chain reaction (PCR) and also
      studied alternative use of multiple exons 1 of its gene, which is involved in
      tissue specific expression of aromatase in human. RESULTS: The amount of
      aromatase mRNA determine by RT-PCR assay in 6 cases tended to be highest in pons,
      thalamus, hypothalamus and hippocampus. Analysis of multiple exons 1 revealed
      that 1f, considered specific for brain, as well as 1b (fibrolast type) and 1d
      (gonadal type), were expressed. 1d and 1f tended to be utilized in hypothalamus,
      thalamus and amygdala. The amount of overall mRNA expression was also higher in
      hypothalamus, thalamus and amygdala than in other regions of the brain. There
      were no differences of utilization of exons 1 and mRNA expression of aromatase
      between female and male brain. CONCLUSIONS: These results demonstrate that
      aromatase is expressed widely in various regions of human brain tissues in both
      men and women.

PMID- 9578824
TI  - Radiotherapy for non-function pituitary tumours.
AB  - OBJECTIVE: Pituitary radiotherapy (RT) is often used as adjuvant treatment in the
      post-operative period for patients with clinically non-functioning pituitary
      tumours (NFTs). There is a distinct lack of objective data, however, describing
      the efficacy of RT in preventing the regrowth of these tumours. We have therefore
      determined whether the recurrence rate for NFTs is significantly lower in
      patients treated with post-operative RT compared with that observed in patients
      not treated with RT. PATIENTS AND METHODS: A retrospective case notes review was
      performed on 126 patients with NFTs treated at two institutions in the UK. One
      hospital routinely administered RT within 12 months of initial pituitary surgery
      whereas the other used post-operative RT only rarely. The main outcome measure
      was regrowth of pituitary tumours following surgery in patients who did or did
      not receive post-operative RT. RESULTS: There was no significant difference
      between patients who received RT versus those who did not in terms of age, sex,
      initial tumour size or mode of operation. The actuarial progression-free survival
      was 93% at both 10 years and at 15 years for the RT treated group, and was 68%
      and 33%, respectively, for the non-RT-treated group. Using Cox's model for
      proportional hazard analysis, we found the only prognostic factor for NFT
      regrowth was the administration of pituitary RT (P < 0.00005). CONCLUSIONS:
      Radiotherapy administered within 12 months of initial pituitary surgery for non
      functioning pituitary tumours significantly reduces the risk of tumour regrowth.
      It remains to be determined whether sequential MRI scanning can help delineate
      those patients who should receive radiotherapy following pituitary surgery for
      non-functioning pituitary tumours.

PMID- 9578826
TI  - Long-term follow-up of bone mineral density and bone metabolism in transsexuals
      treated with cross-sex hormones.
AB  - OBJECTIVE: It is unknown whether long term cross-sex hormone treatment affects
      the human skeleton. We monitored bone mineral density and biochemical markers of
      bone turnover for 28-63 months in 20 male-to-female transsexuals (M-->F) treated
      with anti-androgens and oestrogens, and 19 female-to-male transsexuals (F-->M)
      treated with androgens. They underwent gonadectomy 13-35 months after the start
      of cross-sex hormone administration. DESIGN: Bone mineral density (BMD) and the
      markers of bone turnover osteocalcin, alkaline phosphatase, fasting urinary
      calcium/creatinine and hydroxyproline/creatinine, were measured at baseline,
      after 1 year and after 28-63 months of cross-sex hormone administration. RESULTS:
      In oestrogen-treated M-->F, variables of bone turnover decreased significantly
      with consecutive measurements. BMD had increased significantly after 1 year, but
      decreased again to baseline levels after 28-63 months of cross-sex hormones. In F
      ->M, alkaline phosphatase levels increased during the first year. BMD did not
      change during the first year but had decreased significantly after 28-63 months
      following ovariectomy. In both M-->F and F-->M, the change of BMD correlated
      inversely with serum LH and FSH levels. Of all biochemical variables LH levels
      appeared to be the best predictor of loss of BMD; in the long-term LH levels were
      more elevated in testosterone-treated F-->M than in oestrogen-treated M-->F
      transsexuals. CONCLUSION: In M-->F, oestrogen treatment prevented bone loss after
      testosterone deprivation. In F-->M the testosterone dosage used, associated with
      a decline in serum oestradiol levels, was unable to maintain bone mass fully in
      all subjects in the longer term. The inverse relationship between BMD and serum
      LH levels suggests that the dose of hormone replacement has been too low in
      subjects with a decline in their BMD. Its cause might be underdosing or non
      compliance in some patients. We propose that serum LH levels may be used as a
      measure of the adequacy of replacement with sex steroids.

PMID- 9578825
TI  - Erythrocyte insulin-like growth factor-L binding in younger and older males.
AB  - OBJECTIVE: Insulin-like growth factor-1 (IGF-l) levels are lower in older
      compared with younger subjects. We tested the hypothesis that the reduction in
      circulating IGF-l would be accompanied by upregulation in tissue IGF-l binding in
      at least some tissues. We tested erythrocyte IGF-l binding since blood is an
      accessible tissue in humans, and there is growing evidence to suggest that
      erythrocyte IGF-l binding is influenced by circulating IGF-l. DESIGN AND
      PATIENTS: We compared 9 healthy older males (61-68 years old) with 9 healthy
      younger males (15-19 years old). MEASUREMENTS: Standard techniques were used to
      assay circulating IGF-l and IGF binding proteins 1-5 (IGFBPs 1-5). Erythrocyte
      IGF-l binding was first measured by studies in which native [125l]-IGF-l was
      displaced with unlabelled native IGF-l. In order to determine a possible role for
      IGF binding proteins (IGFBP), native [125l]-IGF-l was displaced with des-(1-3)IGF
      1, which binds with IGF receptors but not IGFBPs. RESULTS: As expected,
      circulating IGF-l was significantly lower in the older compared with the younger
      subjects. In addition, IGFBP-3 and 5 were significantly lower, and IGFBP-4
      higher, in older compared with younger subjects. When native [125l]-IGF-l was
      displaced with unlabelled native IGF-l, the number of IGF-l binding sites per
      erythrocyte was higher in the older subjects (43 +/- 5 vs. 18 +/- 2, older vs.
      younger, respectively; P < 0.05). In contrast, when native [125l]-IGF-l was
      displaced with des-(1-3), IGF-l binding capacity was not different between the
      two age groups. CONCLUSIONS: Erythrocyte IGF binding was increased in older
      compared with younger subjects. Surprisingly, the mechanism of the increase may
      not be a simple up regulation of IGF-l receptors in response to reduced
      circulating IGF-l, but possibly by an increase in the levels of as yet
      unidentified erythrocyte membrane-associated IGF binding proteins.

PMID- 9578827
TI  - Tuberculous Addison's disease: lack of normalization of adrenocortical function
      after anti-tuberculous chemotherapy.
AB  - OBJECTIVE: Tuberculosis of the adrenal glands is a common cause of Addison's
      disease in developing countries. We conducted a study to determine if treatment
      of such patients with modern anti-tuberculous chemotherapy would lead to an
      improvement in plasma cortisol and aldosterone levels. DESIGN: Prospective study.
      PATIENTS: 5 patients with Addison's disease secondary to tuberculosis.
      MEASUREMENTS: Basal and ACTH stimulated plasma cortisol and aldosterone levels
      were measured prior to instituting anti-tuberculous chemotherapy, as well as one
      month after its conclusion. Four patients were again studied over the next 2-5
      years. RESULTS: Peak plasma cortisol levels prior to treatment were markedly
      reduced (range, < 14-110 mumol/l). There was no improvement one month (< 14-143
      mumol/l) or 2-5 years (< 14-69 mumol/l) after completing anti-tuberculous
      chemotherapy. Peak plasma aldosterone at diagnosis was < 56-210 pmol/l; it was
      undetectable in 4 patients. No improvement was observed one month (< 56-210
      pmol/l), or 2-5 years (< 56-389 pmol/l) after stopping anti-tuberculous
      chemotherapy. Plasma aldosterone levels at both these time points were far lower
      than those in control subjects (median 736 pmol/l, 560-1512 pmol/l; p < 0.01).
      One patient had an increase in peak aldosterone from < 56 pmol/l to 389 pmol/l,
      though peak cortisol actually declined in this subject (from 110 mumol/l to 69
      mumol/l). CONCLUSIONS: Treatment of tuberculous Addison's disease with anti
      tuberculous chemotherapy does not lead to normalization of ACTH stimulated plasma
      cortisol or aldosterone levels during the 2-5 year period of study. However,
      prolonged follow up with regular adrenal function tests is warranted in all such
      patients.

PMID- 9578828
TI  - Positive association between circulating free thyroxine and insulin-like growth
      factor l concentrations in euthyroid elderly individuals.
AB  - OBJECTIVE: Previous studies have shown marked changes in circulating insulin-like
      growth factor-l (IGF-l) levels in hypo- and hyperthyroid patients. In this study
      we examined whether the circulating concentration of IGF-l may also be affected
      by normal thyroid hormone levels. DESIGN: A cross-sectional study of thyroid
      hormones and plasma IGF components in a population-based sample. PATIENTS: 50-80
      year-old men (n = 262) and women (n = 218) with normal concentrations of serum
      free thyroxine (fT4), free triiodothyronine (fT3) and thyrotrophin (TSH).
      MEASUREMENTS: Plasma concentrations of IGF-l, IGF-ll and IGFBP-3, and serum
      concentrations of TSH, fT3 and fT4. RESULTS: Serum fT4 values were weakly
      positively correlated and serum TSH levels were inversely correlated with
      circulating IGF-l concentrations. The associations persisted after adjustment for
      age and ideal body weight. CONCLUSIONS: Our data demonstrate that thyroid
      hormones are positively correlated to IGF-l plasma levels even under
      physiological conditions. However, thyroid hormones explain only 1-2% of the
      normal variability of circulating IGF-1.

PMID- 9578829
TI  - Luteinizing hormone secreting adrenal tumour as a cause of precocious puberty.
AB  - A boy aged 6 years presented with genital precocity, enlarged testes and advanced
      linear growth. An ovoid mass 3-4 cm in diameter was identified by MRI scan in the
      right adrenal gland. Serum concentrations of LH, testosterone, alpha-subnuit,
      dehydroepiandrosterone sulphate, androstenedione and oestradiol were persistently
      elevated. LH was unresponsive to bolus i.v. injection of GnRH or to GnRH analogue
      therapy. Serum FSH was normal. After removal of the adrenal tumour, serum LH,
      alpha-subunit, testosterone and adrenal androgen levels fell to normal. In
      incubation medium of cultured disaggregated tumour cells, LH concentrations were
      greater than twice the mean serum concentration and 4-5-fold higher than in the
      medium of cultured non-neoplastic adrenal cells. Specific immunostaining of the
      tumour was positive for LH and alpha-subunit in many areas and these were not
      found in the adjacent non-neoplastic adrenal. Testicular biopsy showed almost
      complete spermatogenesis although germinal cell types were numerically lower than
      in normal men. These findings are consistent with an adrenocortical adenoma
      secreting LH being the cause of the patient's precocious puberty.

PMID- 9578830
TI  - Increased prevalence of Helicobacter pylori infection in females treated with
      dopaminergic drugs for hyperprolactinaemia.

PMID- 9578831
TI  - Employment/unemployment among patients suffering pituitary disease.

PMID- 9578832
TI  - More about genetically modified tumour vaccines.

PMID- 9578833
TI  - Therapeutic gene targeting.
AB  - Gene targeting is the use of homologous recombination to make defined alterations
      to the genome. One of the possible outcomes of gene targeting is the accurate
      correction of genetic defects, and this would make it the ideal method of gene
      therapy for single gene disorder. While gene targeting has been achieved both in
      human cell lines and in nontransformed, primary human cells, its low efficiency
      has been a major limitation to its therapeutic potential. Gene therapy in vivo
      gene targeting is there for impractical without dramatic improvements in
      targeting efficiency. Ex vivo approaches might more realistically be considered,
      but would benefit from progress in the isolation and growth of somatic stem cells
      and improvements in targeting efficiency. We provide here a brief review of the
      challenges of gene therapy by gene targeting. This is followed by a critical
      overview of recent developments in gene targeting techniques, and in our
      understanding of the underlying processes of homologous and nonhomologous
      recombination.

PMID- 9578834
TI  - Enhancement of replication of genetically engineered herpes simplex viruses by
      ionizing radiation: a new paradigm for destruction of therapeutically intractable
      tumors.
AB  - Human U-87 malignant glioma xenografts in mice were exposed to ionizing
      radiation, inoculated with a herpes simplex virus 1 mutant R3616 lacking both
      copies of the gamma 34.5 gene, or received both virus and radiation. Dual
      treatment caused a significantly greater reduction in volume or total regression
      of tumors than either radiation or infection alone. The significantly enhanced
      oncolytic effects of the combined treatment correlate with two-to five-fold
      enhanced replication in irradiated tumor cells than in tumors receiving virus
      only. In addition, in situ hybridization with viral DNA probes showed that
      infected tumor cells were the dominant landscape of irradiated tumors and much
      less apparent in the nonirradiated tumors administered this virus.

PMID- 9578836
TI  - High adenoviral loads stimulate NF kappaB-dependent gene expression in human
      vascular smooth muscle cells.
AB  - Replication-deficient adenoviral vectors have been widely used for gene transfer
      with the aim of delivering genes of interest to investigate their function and
      potentially to treat human disease. The ability to critically evaluate the
      biological role of a gene of interest, using adenovirus-based vectors, has been
      hampered by the development of local inflammation at the site of delivery. We
      have demonstrated that high multiplicity infection of human VSMCs with a
      replication-deficient adenoviral vector expressing no transgene leads to
      activation of the transcription factor NF kappa B. Activation of NF kappa B by
      this mechanism was able to augment gene expression from the human cytomegalo
      virus immediate-early promoter (CMV-IEP) and induce expression of the adhesion
      molecule ICAM-1 in human VSMCs. These effects were inhibited by pretreatment with
      N alpha-p-tosyl1-L-lysine chloromethyl ketone (TLCK), a serine protease inhibitor
      known to inhibit the activation of NF kappa B. This important effect of the
      vector itself may have profound implications when replication-deficient
      adenoviral vectors are used for experimental gene transfer at a high multiplicity
      of infection.

PMID- 9578835
TI  - A fluorescence video-endoscopy technique for detection of gene transfer and
      expression.
AB  - The green fluorescent protein (GFP) has previously been adapted as a reported for
      gene transfer and expression in mammalian cells in culture and in tissue
      sections. Herein is described a new method for detecting GFP in situ within
      epithelia accessible to fiberoptic endoscopy by incorporating fluorescent filters
      for detection of GFP into an existing fiberoptic endoscopy system. This device
      was used to detect expression of GFP from adeno-associated virus (AAV; does of 3
      x 10(7) IU) and adenovirus (Ad; does of l x 10(9) to 1 x 10(10) p.f.u.) vectors
      within the bronchial epithelium of New Zealand white rabbits. GFP expression was
      confirmed by fluorescence-activated cell sorting (FACS), direct fluorescence
      microscopy of cytospin preparations of brushed cells, and by fluorescence
      microscopy of fixed tissue sections. This reporter gene/detection system was then
      used to track the time course of expression of the AAV vector in the bronchial
      epithelium over the first 30 days after administration. The transduction
      frequency in the treated region of the epithelium peaked at around 50% at 21 days
      after transduction. Vector expression was still present at around 20% efficiency
      at 30 days after administration. This example indicates how this method could be
      used to reliably track gene transfer in living animals or patients.

PMID- 9578837
TI  - Comparison between intratracheal and intravenous administration of liposome-DNA
      complexes for cystic fibrosis lung gene therapy.
AB  - Intratracheal (i.t.) and intravenous (i.v.) delivery of DNA-vector formulations
      are two strategies to obtain gene transfer to the lung, it is still uncertain,
      however, which of these two modes of delivery will be more effective in the
      treatment of cystic fibrosis and other lung diseases. In this study, we attempted
      to optimize formulations of the cationic liposome DODAC:DOPE
      (dioleoyldimethylammonium-chloride: dioleoylphosphatidylethanolamine) complexed
      to plasmids encoding chloramphenicol acetyltransferase for i.t. and i.v.
      injection into CD-2 mice and compared the two methods. Our results showed that
      both methods conferred reporter gene expression in the lung that was
      significantly higher relative to injection of plasmid DNA alone. Expression using
      either mode of administration was maximal 24 h after injection and declined to
      around 10% of day 1 levels 2 weeks after injection. For i.v. delivery of DODAC.
      DOPE-DNA complexes multilamellar vesicles were more effective than large
      unilamellar vesicles in all organs investigated. Recombinant DNA could be
      detected in the distal lung region following either route of administration.
      However, i.t. administration predominantly led to DNA deposition in epithelial
      cells lining the bronchioles, e.g. in clara cells, whereas i.v. administration
      resulted in DNA deposition in the alveolar region of the lung including type II
      alveolar epithelial cells.

PMID- 9578838
TI  - Suppression of the immune response to an adenovirus vector and enhancement of
      intratumoral transgene expression by low-dose etoposide.
AB  - Adenoviral vectors are commonly used in gene therapy trials because of their
      efficiency in gene transfer. However, their use is limited by cellular and
      humoral immune responses that result in temporary transgene expression and
      reduced efficacy of repeated vector administration. We hypothesized that certain
      oncolytic agents commonly used to treat cancer patients could suppress the immune
      response to adenoviral vectors, and enable repeated adenovirus-mediated cancer
      gene therapy. Etoposide and cyclophosphamide were tested for their ability to
      suppress the humoral and cellular immune responses to an adenoviral vector in
      immunocompetent C3H mice. Intratumoral transgene expression was monitored in
      adenovirus-immunized animals treated with etoposide or cyclophosphamide.
      Neutralizing antibodies to adenovirus and cytotoxic T lymphocyte (CTL) lysis of
      virally transduced cells were significantly suppressed in mice treated with
      etoposide at 2 or 10 mg/kg/day or cyclophosphamide at 10 mg/kg/day compared with
      untreated mice (P < 0.05). Significantly larger areas of gene transduction were
      observed in treated animals compared with untreated mice or the mice treated with
      cyclophosphamide at 2 mg/kg/day (P < 0.05). Our results suggest that repeated
      adenovirally mediated gene therapy is achievable in cancer patients who are
      concurrently undergoing treatment with chemotherapy.

PMID- 9578840
TI  - Pseudotyping of Moloney leukemia virus-based retroviral vectors with simian
      immunodeficiency virus envelope leads to targeted infection of human CD4+
      lymphoid cells.
AB  - In view of our recent findings that a truncated form of the envelope (Env)
      glycoprotein of human immunodeficiency virus type 1 (HIV-1) was efficiently
      incorporated into MoMLV particles, we studied the generation of Moloney murine
      leukemia virus (MoMLV)/simian immunodeficiency virus (SIV) pseudotypes. Unlike
      HIV-1, both the wild-type SIV Env and a truncated form, which lacks most of the
      cytoplasmic domain of the transmembrane glycoprotein, were incorporated into
      MoMLV particles and generated infectious retroviral vectors which could transduce
      CD4+ sMAGI macaque cells. The infection depended on target cell CD4 expression,
      and was neutralized by both soluble CD4 and sera from SIV-infected macaques. We
      also observed pseudotype-mediated gene transfer of a green fluorescent protein
      marker into the CD4+ CEMX174 and C8166 lymphoid cell lines. More importantly,
      primary human lymphocytes were also successfully transduced ex vivo by MoMLV/SIV
      pseudotypes, albeit at lower efficiency, and gene transfer was specifically
      restricted to the CD4+ subset. These findings demonstrate that MoMLV/SIV
      pseudotypes can be used to transduce cells which are susceptible to SIV
      infection, and thus might be advantageously employed in animal models for direct
      in vivo delivery of gene therapy-based approaches.

PMID- 9578839
TI  - Prevention of late effects of irradiation lung damage by manganese superoxide
      dismutase gene therapy.
AB  - Organ and tissue damage caused by ionizing irradiation is directly related to
      volume irradiated, total dose and dose rate. The acute effects are in part
      mediated by cellular activation of early response genes, including those for
      transcriptional activators of genes for humoral cytokines. In the lung, as in
      other organs, recovery from the acute effects of ionizing irradiation does not
      always correlate with prevention of the critical late effects, including
      fibrosis, which contribute to organ failure. An interventional technique by which
      to protect normal organs from the late effects of irradiation has remained
      elusive. We now demonstrate that overexpression of a transgene for human
      manganese superoxide dismutase (MnSOD) delivered by plasmid-liposome, or
      adenovirus to the lungs of C57BL/6J or Nu/J mice, respectively, before
      irradiation exposure, decreases the late effects of whole lung irradiation
      (organizing alveolitis/fibrosis). These data provide a rational basis for the
      design of gene therapy approaches to organ protection from irradiation damage.

PMID- 9578841
TI  - Gene therapy for cystic fibrosis: a psychosocial study of trial participants.
AB  - As yet little is known of psychological aspects of gene therapy. This pilot study
      aimed to investigate the attitudes, expectations, knowledge and psychological
      functioning of participants in a phase l safety trial of a single application of
      gene therapy to cystic fibrosis patients. Sixteen patients were assessed before
      and after the trial and at a 16 week follow-up using a semi-structured
      qualitative interview. They completed the Family Assessment Scale, the CF-12
      quality of life measure and repeat measures of the Hospital Anxiety and
      Depression Scale and SF-36. Most patients had an emotionally driven optimism
      about gene therapy and few complaints about the procedures in a nasal trial. The
      majority of subjects were in good psychological/health A significant minority had
      anxiety disorders and this group were more likely to have concerns over the
      safety and promise of gene therapy. A preference was expressed for the potential
      of gene therapy over heat-lung transplantation. Results suggest that there are
      unlikely to be major psychological contraindications to proceeding with gene
      therapy research in this patient group. Patients with anxiety disorders may need
      special consideration. Qualitative data collected in this pilot study can now be
      used to develop survey questions for large scale studies.

PMID- 9578842
TI  - Tumour cell expression of B7 costimulatory molecules and interleukin-12 or
      granulocyte-macrophage colony-stimulating factor induces a local antitumour
      response and may generate systemic protective immunity.
AB  - Previously, we showed that expression of B7-1 in CMT93 murine colorectal tumour
      cells inhibited their growth in immunocompetent animals. However, this did not
      result in any significant increase in systemic protective immunity, relative to
      that elicited by the parental tumour. To potentiate the effects of B7-1 on
      systemic immunity. Interleukin-12 (IL-12) or granulocyte-macrophage colony
      stimulating factor (GM-CSF) was co-expressed with this molecule. These
      combinations of immunostimulatory molecules were effective in eliciting systemic
      immunity. We also show that expression of B7-2 led to a local antitumour response
      as well as significantly raised systemic immunity. In another tumour model. K1735
      minutes melanoma, which is moderately immunogenic, tumours secreting GM-CSF alone
      were as effective as the parental tumours in generating protective immunity.
      Previously, we described the deleterious effect of B7-1 expression on protective
      immunity. Co-expression of GM-CSF did not counteract this consequence of B7-1
      expression. Expression of IL-12 was extremely effective in causing rejection of
      inoculated tumour cells, but evoked only minimal protective systemic immunity.
      These results suggest that combing costimulatory molecules and cytokines may be a
      useful therapeutic approach in some, but not all, tumours.

PMID- 9578843
TI  - Gene therapy targeting cord blood-derived CD34+ cells from HIV-exposed infants:
      preclinical studies.
AB  - Hematopoietic CD34+ cells from placental and umbilical cord blood (PUCB) can be
      valuable vehicles for gene therapy of immunodeficiencies and genetic disorders.
      We have conducted preclinical studies towards the treatment of HIV-1-infected
      infants with genetically 'immunized' CD34+ cells derived from PUCB using anti-HIV
      1 hairpin ribozyme genes. PUCB was collected from 10 newborns of HIV-1-positive
      mothers. CD34+ cells were enriched with a modified procedure using Dynal
      immunomagnetic beads and chymopapain, stimulated with stem cell factor (SCF), IL
      3 and IL-6, and transduced using cell-free recombinant retroviral vector (MJT)
      expressing a ribozyme against the U5 region of HIV-1. No significant differences
      were observed in the growth pattern of CD34+ cells from normal infants, HIV-1
      exposed infants or infants confirmed to be infected by HIV-1. The transduction
      efficiency of the CD34+ cells from all the infants was also comparable. MJT
      transduced CD34+ cells from an HIV-1-infected infant were maintained in a liquid
      culture system for 4 weeks, and the progeny macrophage cells were challenged with
      the monocyte-tropic laboratory strain, HIV-Bal, or the HIV-1 isolate from the
      infant's mother. Significant inhibition of virus replication was observed in
      ribozyme-transduced cells. Thus, we have demonstrated efficient and stable gene
      transfer into progenitor cells from the cord blood of HIV-1-exposed or -infected
      infants and shown that protection from HIV-1 infection was conferred to the
      progeny cells produced by CD34+ cells transduced with the anti-HIV ribozyme gene
      construct.

PMID- 9578844
TI  - Gene transduction for disseminated intraperitoneal tumor using cationic liposomes
      containing non-histone chromatin proteins: cationic liposomal gene therapy of
      carcinomatosa.
AB  - Cationic liposome-mediated gene therapy of cancer has been examined in a
      disseminated intraperitoneal tumor model. A combination of the strong CAG
      promoter-enhancer unit and high mobility group 1,2 (HMG-1,2) proteins has been
      used to improve transfection efficiency. The optimal deoxyribonucleic acid (DNA)
      and HMG-1,2 concentration ratio was determined in in vitro studies. Subsequently,
      we administered the liposome-DNA-HMG-1,2 complex intraperitoneally to tumor
      bearing nude mice and defined the most efficient concentration of liposomes.
      Using this approach, the median survival of tumor bearing nude mice was prolonged
      by the administration of a human tumor necrosis factor-alpha (TNF-alpha) gene
      inserted into a eukaryotic strong expression vector (pcagTNF-alpha) and
      exogenously added interferon-gamma (INF-gamma) (72 +/- 3 days: mean +/- s.e.). By
      contrast, survival was 36 +/- 3, 39 +/- 3 and 46 +/- 4 days in group receiving
      the TNF-alpha gene inserted in the reverse orientation (pcagTNF-alpha R) and
      normal saline (NS), pcagTNF-alpha R and INF-gamma and pcagTNF-alpha and NS,
      respectively. These results demonstrate an efficient approach for gene therapy of
      disseminated intraperitoneal cancer.

PMID- 9578845
TI  - Anti-tumor immunity induced by murine melanoma cells transduced with the
      Mycobacterium tuberculosis gene encoding the 38-kDa antigen.
AB  - The Mycobacterium tuberculosis Ag38 gene, which encodes a highly immunogenic
      protein, was cloned into a retroviral vector in-frame with the leader and the
      transmembrane portion of the nerve growth factor receptor, and transduced into
      murine melanoma cell line B16-B78. Significant protection was observed in mice
      immunized with the transduced melanoma cells and subcutaneously challenged with
      parental melanoma cells since only 20% of mice developed tumors. Necroscopy of
      mice immunized with the transduced melanoma cells revealed dramatic inhibition of
      experimental metastases induced by intravenous (i.v.) inoculation of parental
      melanoma cells. Moreover, vaccination with transduced cells significantly
      prolonged survival of mice challenged i.v. with parental melanoma cells. These
      data indicate that the presence of the mycobacterial 38-kDa protein greatly
      enhances immunological recognition of structures expressed by the parental
      melanoma cells. Comparison of Th1 and Th2 responses in mice immunized with
      parental melanoma cells versus mice receiving the transduced cells revealed a
      clear predominance of Th1 responses when the Ag38 protein was endogenously
      expressed. This transduction approach may represent a promising immunotherapeutic
      strategy for the treatment of cancer patients.

PMID- 9578846
TI  - Cloning and expression of murine IFN beta and a TNF antagonist for gene therapy
      of experimental allergic encephalomyelitis.
AB  - Immunomodulation of an ongoing autoimmune disease can be achieved by inhibitory
      cytokines or cytokine inhibitors such as TNF antagonists, delivery by gene
      therapy. The aim of this study was to design and test plasmid and retrovirus
      vectors expressing the mouse IFN beta gene and a chimeric protein containing the
      extracellular domain of human p55 TNF receptor linked to a murine Ig. These
      vectors were transiently expressed in COS-7 cells and permanently in amphotropic
      packaging cell lines or ABH mouse immortalized fibroblasts. Expression levels
      were assessed by ELISA. Western blotting and biological activity. In order to
      achieve tissue-specific expression in the CNS, the IFN beta gene was cloned and
      expressed under the control of the rat NSE promoter. We evaluated these
      constructs by direct intracranial injections of DNA-liposome complexes during the
      induction phase of experimental allergic encephalomyelitis, a murine model of
      multiple sclerosis, with therapeutic benefit.

PMID- 9578847
TI  - Retroviral interleukin-7 gene transfer into human dendritic cells enhances T cell
      activation.
AB  - Tumor vaccination with dendritic cells (DC) presenting tumor antigens to T cells
      is a promising approach in immunotherapy. The aim of this study was to enhance T
      cell stimulatory ability of human DC by retroviral expression of the interleukin
      7 (IL-7) gene. IL-7 has been shown to provide a potent costimulatory signal for
      the proliferation of T cells and the generation of cytotoxic T cells (CTL). DC
      were generated from human peripheral blood mononuclear cells (PBMC). DC were
      analyzed by light- and electron-microscopy, immunophenotype (CD1a+, CD14-, CD80+,
      CD86+, HLA-DR+) and functional assays. According to these criteria, 75-85% of the
      cells were DC. The cells did not produce measurable amounts of IL-7 spontaneously
      nor did they express the IL-7 receptor. A retroviral IL-7 expression vector was
      constructed. Retroviral infection was performed with either the LXSN-hIL-7 vector
      of its variant LXSN. Using the LXSN-hIL-7 vector, IL-7 production of 2296
      pg/10(6) cells/24 h could be achieved on average. Transduction of DC was
      confirmed by RT-PCR in a CD1a-enriched cell fraction. Transduction efficiency by
      a control virus coding for beta-galactosidase was about 30%. In autologous mixed
      lymphocyte reaction (MLR), IL-7 transduced DC augmented T cell proliferation by a
      factor of two compared with unmodified or mock-transfected DC, and in allogeneic
      MLR there was a 2.7-fold increase in T cell proliferation. The increase in T cell
      proliferation could be correlated to IL-7 secretion by DC. Dendritic cells that
      have been simultaneously peptide-loaded and gene-modified to secrete IL-7 are a
      potential tool to amplify activation of tumor-specific T cells.

PMID- 9578848
TI  - The efficient expression of intravascularly delivered DNA in rat muscle.
AB  - Previous studies have demonstrated that muscle can take up and express naked DNA
      or RNA. This study demonstrates that the pDNA can be delivered to and expressed
      within skeletal muscle when injected rapidly, in a large volume and when all
      blood vessels leading into and out of the hindlimb are occluded. The additional
      use of collagenase, papaverine and ischemia raised expression moderately but was
      not critical. These results demonstrate that a nonviral method can lead to high
      levels of expression in the muscles of adult animals large than mice.

PMID- 9578849
TI  - Long-term in vivo cochlear transgene expression mediated by recombinant adeno
      associated virus.
AB  - Adeno-associated virus (AAV) integrated transgene expression within guinea pig
      cochlea has been previously documented. This article extends these studies by
      characterizing the AAV-mediated gene transfer for duration of transgene
      expression within the cochlea and its effect upon cochlear cytoarchitecture over
      a period of 6 months. All animals infused with AAV expressed the transgene
      product, bacterial beta-galactosidase (beta-gal) enzyme, in the spiral limbus,
      spiral ligament, spiral ganglion cells and the organ of Corti at 2-24 weeks after
      infusion. However, the level of beta-gal expression, as determined from intensity
      of immunoreactivity, was relatively lower at 24 weeks as compared with 2 weeks.
      The cellular and tissue architecture within the AAV-beta-gal perfused cochleae,
      harvested 2-8 weeks after AAV infusion, was generally intact, ie free from
      inflammation and cellular degeneration. However, cellular degeneration and
      degradation was apparent in the cochleae of some but not all animals harvested at
      12 and 24 weeks after AAV infusion.

PMID- 9578850
TI  - Establishment of complement-resistant retroviral vector by homologous restriction
      factor 20 gene.
AB  - Homologous restriction factor 20 (HRF20, CD59) is one of the complement
      regulatory factors. In this study, the complement-resistant retroviral vector,
      which possesses the HRF20 gene as a selection gene, was constructed and examined.
      The virus-producing cell, transduced with complement-resistant retroviral vector,
      was established after complement-dependent selection. NIH3T3 and PK15 cells
      transduced with this virus-producing cell were successfully selected by
      complement-dependent selection, which showed significant expression of the HRF20
      antigen. In addition, these cells, transduced with tissue plasminogen activator
      (tPA) cDNA using complement-resistant retroviral vector, expressed tPA antigen
      after complement-dependent selection. These findings suggest that complement
      resistant retroviral vector can be used for the double transduction of HRF20, as
      well as other genes.

PMID- 9578852
TI  - Clinical governance: a statutory duty for quality improvement.

PMID- 9578851
TI  - Antitumoral effect of E1B defective adenoviruses in human malignant cells.

PMID- 9578853
TI  - Evidence into practice, experimentation and quasi experimentation: are the
      methods up to the task?
AB  - OBJECTIVE: Methodological review of evaluations of interventions intended to help
      health professionals provide more effective and efficient health care, motivated
      by the current experience of NHS Research and Development in England. Emphasis
      upon the forms of research appropriate to different stages in the development and
      evaluation of interventions, the use of experimental and quasi experimental
      designs, the methods used in systematic reviews and meta analyses. METHOD: A
      proposed development process is derived from that used in the development of
      drugs. The strengths and weaknesses of different experimental and quasi
      experimental designs are derived from published methodological literature and
      first principles. Examples are drawn from the literature. RESULTS: Like
      pharmaceuticals, implementation interventions need to go through several stages
      of development before they are evaluated in designed experiments. Where there are
      practical reasons that make random allocation impossible in quantitative
      evaluations, quasi experimental methods may provide useful information, although
      these studies are open to bias. It is rare for a single study to provide a
      complete answer to important questions, and systematic reviews of all available
      studies should be undertaken. Meta analytic techniques go some way towards
      countering the low power of many existing studies, reduce the risk of bias, and
      avoid the subjective approaches that may be found in narrative reviews.
      CONCLUSIONS: The initiative taken by NHS Research and Development in examining
      methods to promote the uptake of research findings is welcome, but will only
      prove helpful if careful attention is paid to the different stages of the
      development process, and different research approaches are used appropriately at
      different stages.

PMID- 9578854
TI  - Trends in cigarette consumption cannot fully explain trends in British lung
      cancer rates.
AB  - STUDY OBJECTIVES: To determine whether British lung cancer (LC) trends are
      adequately explained by cigarette smoking trends, and whether modelling using
      aggregated smoking prevalence estimates can validly replace modelling using
      individual smoking histories. METHODS: Observed LC trends for 1955-1985 for both
      sexes and three age groups were compared with multistage model predictions using
      smoking history data from two surveys (HALS, AHIP). The modelling used the
      individual smoking data directly or aggregated prevalence estimates. It allowed
      for variation in age of starting and stopping smoking, amount smoked, tar levels,
      and environmental tobacco smoke (ETS) exposure. RESULTS: Observed male LC rates
      fell faster than predicted by a model (with the first and penultimate stages
      assumed affected by smoking) that allowed for variation in amount smoked and in
      tar level (with some provision for "compensation"), and was based on aggregated
      smoking data from HALS. The discrepancy equated to an annual change unexplained
      by smoking of -2.4%, -2.8%, and -1.9% for ages 35-44, 45-54, and 55-64. The
      annual unexplained changes were less in women, and reversed at age 55-64; -1.7%, 
      0.8%, and +0.8% for the three ages. They were similar using individual smoking
      histories (-2.6%, -1.8%, and -1.6%; women, -0.9%, -0.5%, and +0.2%). The
      discrepancies were unexplained by plausible alternative multistage parameters,
      full allowance for tar reduction, alternative estimates of amount smoked, or ETS.
      CONCLUSIONS: British LC trends cannot be fully explained by cigarette consumption
      trends, implying factors other than cigarette smoking contribute importantly to
      overall risk. Predictions using aggregated prevalence estimates provide useful
      information.

PMID- 9578855
TI  - Psychosocial work environment and cardiovascular risk factors in an occupational
      cohort in France.
AB  - STUDY OBJECTIVE: Concordant results have been reported in several studies for the
      effects of job stress on cardiovascular disease, but the potential mechanisms of
      these effects have seldom been explored. The aim of this study was therefore to
      examine, in women and men, the cross sectional relations between psychosocial
      work variables (psychological demands, decision latitude, and social support) and
      cardiovascular risk factors (hypertension, hyperlipidaemia, diabetes, overweight,
      smoking, and alcohol consumption). PARTICIPANTS: The original cohort comprised
      20,625 volunteers (men aged from 40 to 50 and women from 35 to 50) employed by
      the French Company Electricite De France-Gaz De France and followed up yearly
      since 1989. The study was restricted to the 13,226 volunteers in the cohort who
      were still working and answered a self administered questionnaire on psychosocial
      work factors in 1995. DESIGN: Data were based on replies to this questionnaire.
      Three psychosocial work environment exposure scores were used to assess
      psychological demands, decision latitude, and social support at work
      respectively. The main outcome measures were the prevalence of hypertension,
      hyperlipidaemia, and diabetes within the previous 12 months, overweight, smoking,
      and alcohol consumption. MAIN RESULTS: Psychosocial work factors were
      significantly associated with hypertension, hyperlipidaemia, overweight, smoking,
      and alcohol consumption, but not with diabetes. In men, low decision latitude was
      associated with hypertension, high decision latitude and high social support with
      overweight, low decision latitude with alcohol consumption. Moreover, the risk of
      hyperlipidaemia increased in men exposed to both high psychological demands and
      low social support. In women, low decision latitude was related to
      hyperlipidaemia, high psychological demands with overweight, high psychological
      demands and high decision latitude with smoking, and low social support with
      alcohol consumption. CONCLUSIONS: These cross sectional results underline the
      potential effects of psychosocial work characteristics on cardiovascular risk
      factors and the differences between the effects of job stress in men and women,
      and confirm the direct mechanisms (through physiological variables) and indirect
      mechanisms (through behavioural risk factors) potentially involved in the
      relation between psychosocial work characteristics and cardiovascular disease.

PMID- 9578856
TI  - Epidemiology of Epstein-Barr virus infection in pre-adolescent children:
      application of a new salivary method in Edinburgh, Scotland.
AB  - STUDY OBJECTIVE: To describe the epidemiology of Epstein-Barr virus (EBV) among
      primary school children by testing saliva with a new EBV capsid antigen "G"
      antibody capture radioimmunoassay (GACRIA). DESIGN: A population based sample of
      7 year old schoolchildren were followed up at age 11. SETTING: 30 randomly chosen
      primary schools in Edinburgh, Scotland. PARTICIPANTS: 552 schoolchildren.
      MEASUREMENTS: Data on risk factors for infection were collected by questionnaire
      at ages 7 and 11. Saliva samples collected at age 11 were examined by GACRIA for
      evidence of previous infection with EBV. For 102 subjects, a second salivary
      specimen collected approximately one month after the first sample was available
      for testing as a measure of the repeatability of the method. MAIN RESULTS:
      Unequivocal results were found in 91% of samples and the repeatability of the
      test was good (kappa = 0.71). Fifty six per cent of children had antibodies to
      EBV. In a logistic regression analysis, independent risk factors for infection
      were sharing a room (odds ratio 1.78, 1.14, 2.79), head of household's social
      class IV/V compared with I (odds ratio 2.87, 1.08, 7.34), and schools serving
      predominantly rented housing estates (odds ratio 2.3, 1.09, 4.84). CONCLUSION:
      This study is the first application of EBV viral capsid GACRIA to salivary
      samples. The method was successfully used to describe the epidemiology of EBV. In
      this study, characteristics of the home seemed to be more important than those of
      the school in determining the likelihood of infection with EBV.

PMID- 9578857
TI  - Case-control study of breast cancer in south east England: nutritional factors.
AB  - OBJECTIVES: To explore dietary risk factors, in particular fat intake, for breast
      cancer, using an approach to reduce recall bias of subjects and so provide a more
      reliable estimate of dietary intake than previous similar studies. DESIGN: A case
      control study of women aged 50-65 years attending the breast assessment clinics
      of the breast screening programme in Southampton and Portsmouth, southern
      England. Data were analysed for all women requiring further clinical procedures;
      all women recalled to have an early rescreen; and a random sample of women found
      to be normal and referred for a routine rescreening appointment (standard
      recall). MEASUREMENTS: An interview obtained information on various lifestyle
      characteristics including smoking and alcohol intake, weight, waist, and hip
      measurements were also taken at the clinic. Women were given a detailed
      questionnaire on food intake to complete at home and return by post. RESULTS:
      1577 women were included in the study: 220 with breast cancer (cases); 179 with
      benign breast disease; 353 early rescreen and 825 given a standard recall
      appointment. There were few differences in nutritional intake between the four
      groups. Logistic regression analyses were carried out comparing the dietary
      intake of cases with that of each control group adjusting for important
      demographic and reproductive factors. Results for the case and standard recall
      comparison are presented. The only non-calorific nutrient to reach significance
      was iron, which was negatively associated with risk (p = 0.03). For fat intake,
      the odds decreased with increasing polyunsaturated fat (p = 0.15), showed no
      trend with monounsaturated fat (p = 0.37) and increased (p = 0.10) with
      increasing saturated fat. No pattern was clear for the other calorie providing
      nutrients. CONCLUSIONS: In line with recent cohort studies, this study has shown
      no evidence to support the hypothesis that dietary fat is an important
      contributor to breast cancer rates. Biases should have been reduced by studying
      subjects from the screening programme who were at an early stage of disease.

PMID- 9578858
TI  - Calculating appropriate target cancer detection rates and expected interval
      cancer rates for the UK NHS Breast Screening Programme. Interval Cancer Working
      Group.
AB  - OBJECTIVES: To enable better monitoring of interim outcome measures in the NHS
      Breast Screening Programme by providing revised targets for cancer detection
      rates, and revised expected interval cancer rates. DESIGN AND SETTING: Expected
      detection rates of invasive cancers at prevalent screen are calculated, using
      estimates of the underlying England and Wales incidence rates and age specific
      prevalence incidence ratios from the Swedish Two County Study. Expected interval
      cancer rates are also derived from this study, and are used to calculate expected
      detection rates at rescreening. RESULTS: The expected invasive cancer detection
      rates at first screen for women aged 50-52 is 3.6 per 1000. The expected rate at
      rescreening for women aged 53-64 is 4.0 per 1000. Expected interval cancer rates
      for women screened from 1995/6 onwards are 0.45 per 1000, 0.65 per 1000, and 1.2
      1.3 per 1000 for the periods within 0-<12, 12-<24, and 24-<36 months of
      screening. CONCLUSIONS: The target cancer detection rates and expected interval
      cancer rates for the NHS Breast Screening Programme have been revised in the
      light of more recent data. Monitoring of the extent to which the programme is
      meeting these revised targets will give a more accurate indication of the
      potential to meet the Health of the Nation target of a 25% reduction in breast
      cancer mortality by the year 2000.

PMID- 9578859
TI  - Effect on attendance at breast cancer screening of adding a self administered
      questionnaire to the usual invitation to breast screening in southern England.
AB  - STUDY OBJECTIVE: The primary aim of the research described in this paper was to
      ascertain whether inclusion of a self administered questionnaire with the usual
      invitation to routine breast screening affected screening uptake. Secondary aims
      included establishing appropriate questionnaire distribution and collection
      methods within the framework of the National Health Service Breast Screening
      Programme and optimisation of questionnaire design. DESIGN: Randomised study.
      SETTING: Oxfordshire and West of London Breast Screening Units.
      PARTICIPANTS/METHODS: 6400 women invited for routine screening mammography were
      individually randomised to receive either the usual breast screening invitation
      alone, or to receive the usual invitation accompanied by a self administered
      questionnaire, to be returned at the time of screening. Participants were then
      followed up and attendance rates at screening were compared between groups. MAIN
      RESULTS: Screening attendance rates were similar in women who did and did not
      receive a questionnaire (71% in each group). Of those who were sent a
      questionnaire and attended for screening, 77% returned a completed questionnaire.
      Screening uptake was not affected by the way in which the questionnaire was
      returned or by whether or not personal details and signed permission for follow
      up were requested. CONCLUSIONS: The inclusion of a self administered
      questionnaire accompanying the invitation to breast screening did not adversely
      affect screening uptake. A high proportion of women completed the questionnaire.

PMID- 9578860
TI  - Is immunising all patients with chronic lung disease in the community against
      influenza cost effective? Evidence from a general practice based clinical
      prospective cohort study in Utrecht, The Netherlands.
AB  - STUDY OBJECTIVE: There is little information on the potential benefit of
      immunising all patients with chronic lung disease in the community against
      influenza. The clinical effectiveness and economic benefit was established of the
      influenza vaccination programme in a general practice based cohort of adult
      patients with chronic lung disease followed up during the 1995/96 influenza A
      epidemic. DESIGN: A prospective cohort study from October 1995 to March 1996.
      SETTING: The study was undertaken in the Utrecht General Practices Network with
      six large group practices, covering a total population of approximately 50,000
      patients in the Netherlands. PATIENTS: Computerised medical records of 1696
      patients with chronic lung disease aged over 18 years with an indication for
      vaccination according to the Dutch GP guidelines were reviewed. MAIN RESULTS: The
      overall attack rate of any complication, including all cause death, low
      respiratory tract infection, and acute cardiac disease was 15%. Exacerbations of
      lung disease were most frequent (13%). Death, pneumonia, and acute cardiac
      disease were mainly limited to patients > or = 65 years. No effectiveness of the
      immunisation programme could be established in patients 18-64 years (n = 1066),
      after controlling for baseline prognosis in multivariable logistic regression
      analysis. In vaccinees > or = 65 years (n = 630), the occurrence of any
      complication was reduced by 50% (95% CI 17, 70%). The economic benefit was
      estimated at 50 Pounds per elderly vaccinee. CONCLUSIONS: This study suggests
      that in the Netherlands immunisation of elderly patients with chronic lung
      disease against influenza is effective and cost-saving, hence these patients
      should be given high priority. More, preferably experimental, studies are needed
      to establish whether adult lung patients under 65 years in the community will
      also benefit from vaccination.

PMID- 9578861
TI  - Mortality from malignant neoplasms in Crete, 1992-1993.

PMID- 9578862
TI  - Unexpected effects of a prior feedback letter and a professional layout on the
      response rate to a mail survey in Geneva.

PMID- 9578863
TI  - Does requesting sensitive information on postal questionnaires have an impact on
      response rates? A randomised controlled trial in the south west of England.

PMID- 9578864
TI  - Life expectancy in Danish women and men related to smoking habits: smoking may
      affect women more.

PMID- 9578865
TI  - Correlates of blood pressure at age 18 in a cohort of Scottish adolescents.

PMID- 9578866
TI  - Seroprevalence of toxoplasmosis in women with repeated abortions in Kashmir.

PMID- 9578868
TI  - Positron emission tomography--a useful imaging technique for otolaryngology, head
      and neck surgery?

PMID- 9578867
TI  - Decreased survival of patients with lung cancer admitted to a teaching hospital
      through the emergency department in Barcelona, Spain.

PMID- 9578869
TI  - Principles of molecular genetics.

PMID- 9578870
TI  - Is primary radiotherapy an appropriate option for the treatment of verrucous
      carcinoma of the head and neck?
AB  - The literature on verrucous carcinoma of the head and neck was reviewed to
      analyse the use of primary radiation therapy in the treatment of this lesion. The
      results emphasize an overall local control rate of 43.2 per cent, and 6.7 per
      cent of true anaplastic transformation following irradiation. Diagnosis remains
      the fundamental problem: without a correct diagnosis of verrucous carcinoma, no
      correct treatment can be applied.

PMID- 9578871
TI  - A randomized prospective trial to compare four different ear packs following
      permeatal middle ear surgery.
AB  - Surgeons choice of an ear pack is dictated by availability, previous training and
      personal preference. There has been no recent prospective study evaluating the
      use of different types of ear packs. This randomized prospective study compares
      the use of BIPP impregnated ribbon gauze (Aurum), Pope wicks (Xomed-Teace),
      silastic sheeting (Dow Corning) and tri-adcortyl ointment (Squibb) as an ear
      dressing following 'clear' middle ear procedures via a permeatal approach. The
      results showed that there was no statistically significant difference in post
      operative pain and discomfort experienced, neither was there any significant
      difference regarding the otolaryngologist's assessment of the degree of canal
      granulation, stenosis or discharge with the above named packs. This study
      concludes that non-traditional dressings such as tri-adcortyl ointment or simply
      a thin silastic sheet placed on the drum are no worse than time honoured BIPP.
      They have, as well, the advantage of being well-tolerated by the patients.

PMID- 9578872
TI  - Acquired medial canal fibrosis.
AB  - Acquired medial canal fibrosis is a discrete clinicopathological entity
      characterized by formation of fibrous tissue in the bony external auditory
      meatus. Over a seven-year period, a total of 14 operative procedures were
      performed on 12 ears involving 10 patients. Four cases had followed otitis
      externa, two were complications of suppurative otitis media, and three cases were
      iatrogenic. The cause could not be identified in three ears involving two
      patients. Treatment entails excision of all the fibrous tissue and involved skin,
      a wide canaloplasty, a meatoplasty, and then reconstruction by split skin graft.
      Two cases of canal cholesteatoma were encountered. Average follow-up of two years
      showed hearing improvement in all patients. The only complication was a
      recurrence of the stenosis in two ears. The paper discusses terminology,
      aetiology, pathophysiology, diagnosis, and principles of treatment of this
      condition.

PMID- 9578873
TI  - Acute granulomatous myringitis.
AB  - This case report describes five cases of acute granulomatous myringitis treated
      during the nine-year period from 1987 to 1996. Otorrhoea and slight otalgia were
      the two major complaints. Findings included the appearance of a granulomatous
      bulge along the handle of the malleus or on the eardrum. No cases displayed
      eardrum perforation. No similarities were noted in patient age, sex or affected
      side. Treatment consisted of removal of the granuloma with a small cup forceps
      plus cauterization with 20 per cent trichloracetic acid. Two or three treatments
      resulted in complete healing, and average time to healing was 30 days, with no
      recurrences. Because it differs so distinctly from the more common chronic
      myringitis--characterized by mild symptoms, erosion and perforation of the
      eardrum with little granulomatous change, and a longer time to healing with
      frequent recurrence--the authors conclude that acute granulomatous myringitis
      should be regarded as a separate entity.

PMID- 9578874
TI  - Tympanoscopy to increase the accuracy of diagnosis in conductive hearing loss.
AB  - The diagnosis of conductive hearing loss is usually based on audiological methods
      and radiology. The aim of our study was to show that there is a useful additive
      method to clarify the findings of diseases with conductive hearing loss. Patients
      (151 ears) with conductive hearing loss were examined using several methods:
      otomicroscopy, air- and bone-conduction threshold,pure tone average, speech
      threshold, speech discrimination, tympanometry and stapedial reflex and
      tympanoscopy. The management of the patients changed in 17 per cent of cases due
      to tympanoscopy. In a group with normal tympanic membrane the movement of the
      stapes during endoscopy was compared to stapedial reflex. Stiff stapes were found
      more often than an abnormal stapedial reflex. Middle ear endoscopy can increase
      the accuracy of diagnosis of conductive hearing loss thus enhancing decision
      making in the case of the patient.

PMID- 9578875
TI  - Stapedectomy for far-advanced otosclerosis.
AB  - Patients with far-advanced otosclerosis (FAO) may appear to be suffering from
      profound sensorineural hearing loss and are frequently directed to cochlear
      implantation programmes. In order to avoid such misdiagnosis, FAO should be
      considered in patients with non-measurable bone-conduction levels and air
      conduction levels exceeding 85 dB. Specific clues can lead the clinician to
      suspect otosclerosis as the aetiology of hearing loss. A review of eight patients
      (nine ears) with FAO who underwent stapedectomy from 1985-1995 reveals that six
      of the eight (75 per cent) who had been unable to use a hearing aid
      preoperatively obtained serviceable hearing with a hearing aid after surgery.
      This confirms that cochlear implantation is not the best treatment for all
      profoundly deaf patients; some are better off with stapedectomy.

PMID- 9578876
TI  - ENT day surgery in England and Wales--an audit by the Royal College of Surgeons
      (Eng.) Comparative Audit Service.
AB  - An audit of day surgery was carried out by the Royal College of Surgeons (Eng.)
      Comparative Audit service. Data from 121 respondents on over 3,962 day cases were
      analysed from both retrospective information and from prospective individual
      patient proformas. The day surgery rate is 31 per cent. The variability of
      facilities for day-surgery, the timing of lists, type of anaesthetic used and
      case-mix are discussed. Outcome and the reasons for admission to an overnight bed
      are analysed. The overall admission rate was found to be 2.8 per cent (range 0.6
      19.5 per cent between consultants). Seventy per cent of ENT day-surgery was
      performed on morning lists which have a lower admission rate than afternoon
      lists. The main reasons for admission are vomiting 30 per cent, haemorrhage 20
      per cent and inadequate recovery from anaesthetic 22 per cent. A more detailed
      analysis of reasons for admission were given for tonsillectomy, adenoidectomy,
      FESS, and grommets. Recommendations are given which might increase the scope of
      safe day-surgery and reduce admission rate.

PMID- 9578877
TI  - Leiomyosarcoma of the auricle: case report and literature review.
AB  - Leiomyosarcoma is a malignant tumour of smooth muscle origin. These tumours are
      rarely encountered in the head and neck region. A case of leiomyosarcoma of the
      auricle is presented. There are two cases of external auditory canal
      leiomyosarcoma in the literature. To our knowledge the present case is the first
      example of leiomyosarcoma of the auricle.

PMID- 9578878
TI  - Cochlear implantation of a Hungarian deaf and blind patient with discharging ears
      suffering from Behcet's disease.
AB  - A case is reported in which a Nucleus 22 channel intracochlear device was
      implanted a deaf/blind Hungarian adult with discharging ears suffering from
      Behcet's disease. Preconditioning surgery was employed three months prior to the
      implantation procedure to ensure a sterile, dry protected environment for the
      electrodes. One month after implantation, the patient exhibited excellent
      auditory discrimination capability at the time of the first switch on. We suggest
      that some deaf/blind individuals may serve as very good candidates for
      intracochlear implantation.

PMID- 9578879
TI  - Verrucous squamous carcinoma of the nasal septum.
AB  - We document only the second reported case of verrucous squamous carcinoma of the
      nasal septum. In both cases previous surgical treatment for assumed squamous
      papillomata had resulted in multiple recurrences necessitating formal surgical
      resection. Our patient has remained tumour-free during long-term follow-up.

PMID- 9578880
TI  - Solitary plasmacytoma of the epiglottis: a case report and review of the
      literature.
AB  - A 59-year-old white male presented with a two-month history of dry cough and
      shortness of breath. At bronchoscopy, a 1 cm mass on the laryngeal surface of the
      epiglottis was found. Immunohistochemical stain of the biopsy specimen revealed a
      monoclonal proliferation of plasma cells. Serological tests revealed normal serum
      immunoglobulin levels, and a bone marrow aspirate and biopsy was also normal; no
      abnormalities were found on serum or urine electrophoresis. He received
      radiotherapy (50 Gy), and was doing well three years following therapy without
      evidence of disease.

PMID- 9578881
TI  - Vocal fold abductor paralysis as a solitary and fatal manifestation of multiple
      system atrophy.
AB  - A patient is presented who had bilateral abductor vocal fold paralysis
      pathologically proven to be due to multiple system atrophy (MSA) in the absence
      of other neurological features. MSA is a degenerative neurological condition that
      includes olivopontocerebellar atrophy, Shy-Drager syndrome and striatonigral
      degeneration. The usual predominant features of MSA are cerebellar ataxia,
      autonomic dysfunction and Parkinsonism. Stridor is present in over one third of
      patients and has been reported previously as a presenting symptom in MSA: however
      previously reported patients have always gone on to develop other neurological
      symptoms. The usual investigations of bilateral abductor vocal fold paralysis
      caused by MSA will not reveal the pathological process and we believe that
      magnetic resonance imaging (MRI) of the medulla and brain stem and autonomic
      function tests are probably the investigations of choice. It is a worthwhile
      exercise attempting to identify MSA as the cause of stridor as the prognosis is
      good in the medium term if appropriate support is offered.

PMID- 9578882
TI  - Primary extramedullary plasmacytoma of the parotid gland: a case report and
      review of the literature.
AB  - Solitary extramedullary plasmacytomas are uncommon malignant neoplasms with a
      great predilection for the upper respiratory tract. Extramedullary plasmacytoma
      involving the parotid gland is an extremely rare condition. This report describes
      the case of a primary extramedullary plasmacytoma arising in the right parotid
      gland of a 63-year-old man. A review of the literature reveals that this disease
      has generally a good prognosis. provided that multiple myeloma has been excluded.
      The treatment of choice should be surgical excision followed by radiotherapy,
      although from this study there is insufficient evidence to suggest that this is
      more effective than surgery alone. All patients must have regular long-term
      follow-up to monitor for recurrence or dissemination, in which event chemotherapy
      may be considered in addition to the other treatment modalities.

PMID- 9578883
TI  - Extra-articular pigmented villonodular synovitis of the temporomandibular joint.
AB  - Pigmented villonodular synovitis, a benign but locally destructive
      fibrohistiocytic proliferative lesion involving tendon sheaths, bursae and
      diarthrodial joints, is distinctly rare in the temporomandibular joint. We report
      one such case occurring in a 42-year-old housewife who presented with a
      progressively enlarging right zygomatic mass for six months. On exploration, an
      orange-brown firm mass, 5 x 3 x 2 cm, was seen adherent to the lateral aspect of
      the capsule of the right temporomandibular joint, and eroding into the inferior
      aspect of the right temporal bone and part of the mandibular condyle. The mass
      was completely excised. Pathological examination showed features typical of those
      of pigmented villonodular synovitis and the lesion was entirely extra-articular
      in location. The patient remained well with no evidence of local recurrence two
      years after operation. Review of the literature and careful analysis of the
      clinicopathological features showed that the vast majority of the reported cases
      of pigmented villonodular synovitis of the temporomandibular joint belonged to
      the extra-articular variant, which is associated with a more aggressive local
      infiltrative behaviour and higher rate of local recurrence than the localized
      type. The recommended treatment for this condition is therefore wide local
      excision, aiming to remove the lesion as completely as possible without producing
      severe disability for the patient.

PMID- 9578884
TI  - B-cell lymphoma with extensive cutaneous involvement presenting to the ENT
      surgeon.

PMID- 9578886
TI  - An unusual cause of acute labyrinthine failure.
AB  - We report a case of a 40-year-old man presenting with acute vertigo and deafness.
      Computed tomography (CT) scanning at initial presentation was normal. However,
      one year later he developed numbness on the right side of his face and
      examination revealed fifth, seventh and eighth cranial nerve palsies as well as
      cerebellar dysfunction. Magnetic resonance imaging (MRI) demonstrated a
      cerebellopontine angle lesion. He underwent near total excision followed by neuro
      axis irradiation. The main mass of the tumour projected into the cerebellopontine
      angle. Histology showed this to be a medulloblastoma. All features of this case
      are unusual; hence we discuss the pathogenesis and management of this very rare
      tumour.

PMID- 9578885
TI  - Multiple malignancies in a patient with bilateral retinoblastoma.
AB  - A case is presented of a patient with bilateral retinoblastoma, treated at
      infancy with surgery, chemotherapy and radiotherapy, who subsequently developed
      at least four additional histologically distinct malignancies: a Ewing sarcoma of
      the left fibula, two extraskeletal osteosarcomas of the left lower extremity, a
      mucoepidermoid carcinoma of the right parotid gland and a squamous cell carcinoma
      of the left paranasal cavity. In addition to retinoblastoma, patients with a
      germline RB-1 mutation are at high risk of second primary malignancies. An
      additive carcinogenic effect of cytotoxic therapy in these patients has been
      assumed. Patients with hereditary retinoblastoma should be under life-long follow
      up programmes including a regular head and neck examination for detection of new
      primaries, especially in the radiation field of the presenting retinoblastoma.

PMID- 9578887
TI  - Giant aneurysm of the petrous internal carotid artery: diagnosis and treatment.
AB  - We report the case of a giant fusiform aneurysm of the petrous internal carotid
      artery in a 15-year-old patient who had presented with headache, hearing loss and
      Horner's syndrome. Definitive radiological diagnosis was made by non-invasive
      imaging techniques, including magnetic resonance angiography (MRA). The aneurysm
      was obliterated by endovascular balloon occlusion following successful tolerance
      of test occlusion of the internal carotid artery.

PMID- 9578888
TI  - Adenocarcinoma of the larynx--a distant metastasis from a rectal primary.
AB  - Laryngeal metastases from remote primary tumours are uncommon. They derive mostly
      from melanomas or renal cell carcinomas. The generally rare laryngeal
      adenocarcinomas can only be classified as metastatic tumours in the presence of a
      distant primary of the same histology. Only five cases of a laryngeal secondary
      originating from adenocarcinoma of the large bowel have been reported in the
      world literature. A further case is presented which to our knowledge is the first
      to arise from the rectum, a site which suggests haematogenous tumour spread. This
      paper emphasizes the need for the search of synchronous metastatic disease and
      discusses the therapeutic options on the grounds of current management of
      singular colorectal secondaries.

PMID- 9578889
TI  - Pleomorphic lipoma of the parotid gland.
AB  - Lipomata are rare tumours of the parotid gland. The pleomorphic lipoma represents
      an unusual histological variant of the benign lipoma. We report a case of a
      pleomorphic lipoma arising in the parotid gland. Only one case of a similar
      nature has previously been recorded. This tumour is benign, was fully excised and
      recurrence is not expected.

PMID- 9578890
TI  - International comparisons of health-care expenditure: a dismal science?

PMID- 9578891
TI  - Management of male osteoporosis: report of the UK Consensus Group.
AB  - Although osteoporosis is generally regarded as a disease of women, up to 30% of
      hip fractures and 20% of vertebral fractures occur in men. Risk factors for
      osteoporotic fractures in men include low body mass index, smoking, high alcohol
      consumption, corticosteroid therapy, physical inactivity, diseases that
      predispose to low bone mass, and conditions increasing the risk of falls. The key
      drugs and diseases that definitely produce a decrease in bone mineral density
      (BMD) and/or an increase in fracture rate in men are long-term corticosteroid
      use, hypogonadism, alcoholism and transplantation. Age-related bone loss may be a
      result of declining renal function, vitamin D deficiency, increased parathyroid
      hormone levels, low serum testosterone levels, low calcium intake and absorption.
      Osteoporosis can be diagnosed on the basis of radiological assessments of bone
      mass, or clinically when it becomes symptomatic. Various biochemical markers have
      been related to bone loss in healthy and osteoporotic men. Their use as
      diagnostic tools, however, needs further investigation. A practical approach
      would be to consider a bone density more than one SD below the age-matched mean
      value (Z < -1) as an indication for therapy. The treatment options for men with
      osteoporosis include agents to influence bone resorption or formation and
      specific therapy for any underlying pathological condition. Testosterone
      treatment increases BMD in hypogonadal men, and is most effective in those whose
      epiphyses have not closed completely. Bisphosphonates are the treatment of choice
      in idiopathic osteoporosis, with sodium fluoride and anabolic steroids to be used
      as alternatives.

PMID- 9578892
TI  - The outcome of peripartum cardiac failure in Zaria, Nigeria.
AB  - We have studied 227 women who had peripartum cardiac failure (PPCF) in Zaria,
      Nigeria, since 1969-72. This follow-up and review of survivors in 1993-95
      depended chiefly on a Zaria woman (A. Abdullahi) and on her careful reporting.
      Overall, 31 (13.7%) were completely lost to follow-up, 17 (7.5%) were thought to
      be alive, and there were data on 179 others (78.8%). Of the 75 known deaths, 55
      were cardiovascular--20 due to PPCF, 31 due to cardiac failure unrelated to
      pregnancy (CF), and four were due to a cerebrovascular accident. PPCF recurred in
      13% of 551 subsequent pregnancies. Thirty-two women had a recurrence of PPCF
      only, and 27 an episode of CF only. Blood pressures rose steadily over the years.
      An enlarged left ventricle on discharge after the index admission predicted a
      poor prognosis. In 1993-5, we compared 100 survivors with 100 non-PPCF controls:
      96 PPCF women but only 50 control women took extra salt (p = 0.0001).
      Significantly more PPCF women than controls had a diastolic pressure of 110 mm Hg
      (p = 0.011). The syndrome is probably provoked in potentially hypertensive women
      by the traditional practices of eating kanwa, which is rich in Na+, taking
      additional excess salt and heating the body after delivery. Evidence is presented
      that PPCF women are potentially hypertensive, and cannot handle the excess
      ingested sodium which therefore leads to hypervolaemia and thus PPCF.

PMID- 9578893
TI  - Post-infection fatigue syndrome following Q fever.
AB  - In 1989, 147 individuals in the West Midlands, UK, were infected with Q fever.
      Five years later, following anecdotal reports of fatigue, we used a questionnaire
      based case-control study to determine the prevalence of chronic fatigue syndrome
      symptoms in this group. Replies from 71 patients were compared with those from
      142 age- and sex-matched controls. Increased sweating (52.9% vs. 31.6%, p =
      0.006), breathlessness (50.7% vs. 30.6%, p = 0.006), blurred vision (34.3% vs.
      17.8%, p = 0.016) and undue tiredness (68.7% vs. 51.5%, p = 0.03) were found in
      controls compared to cases. These findings were similar to those in Australian
      abbatoir workers occupationally exposed to Q fever. CDC criteria for chronic
      fatigue syndrome were fulfilled by 42.3% of cases and 26% of controls. Using
      visual analogue scores, symptoms were more severe in cases than in controls. Our
      findings support the existence of a chronic fatigue state following acute Q
      fever, in a group of patients exposed just once to the organism, and in
      circumstances free of such confounding factors as lawsuits over compensation.

PMID- 9578894
TI  - Antibodies against phospholipids and beta 2-glycoprotein I increase the risk of
      recurrent venous thromboembolism in patients without systemic lupus
      erythematosus.
AB  - We studied the prognostic significance of antiphospholipid antibodies for
      recurrence of venous thromboembolism (VTE), in 71 patients admitted for acute VTE
      (deep-vein thrombosis or pulmonary embolism) in a single internal medicine unit.
      Lupus anticoagulant (LA), antibodies directed against beta 2-glycoprotein I (beta
      2GPI) and antibodies against both beta 2GPI and a mixture of phospholipids
      (cardiolipin, phosphatidylserine and phosphatidic acid) (APAs) were measured. The
      patients were followed-up (mean 4.9 years) to determine the time to the next VTE.
      We found LA in nine patients, anti-beta 2GPI antibodies in seven patients and
      APAs in six patients. The cumulative risk of recurring VTE was higher in patients
      with beta 2GPI-binding antibodies (hazard ratio 12.6, 95% CI 1.5-104.9; p =
      0.0029). The risk associated with APAs was 11.5 (95% CI 1.3-98.9; p = 0.0049) and
      that for LA was 3.7 (95% CI 0.9-15.6; p = 0.055). The risk of VTE recurring was
      higher both in patients with antibodies directed against beta 2GPI, and in
      patients with antibodies directed against beta 2GPI and a mixture of
      phospholipids, than in patients without these antibodies.

PMID- 9578895
TI  - Hodgkin's disease: a population-adjusted clinical epidemiology study (PACE) of
      management at presentation. Northern Region Lymphoma Group.
AB  - Between January 1991 and December 1993, all newly-diagnosed patients with
      Hodgkin's disease in the Northern Health Region (population 3.08 million) were
      entered into a prospective population-based (PACE) study to assess the accuracy
      of staging at diagnosis, and to evaluate treatment and outcome. On histological
      review, 202 patients were confirmed to have Hodgkin's disease, an incidence of
      2.2 per 100,000 per annum. Radiological review revealed that only 12% of patients
      were staged to recognized guidelines. In early-stage disease, treatment outcome
      was comparable to published results in Stage IA disease, but disappointing for
      Stage IIA. This was partly due to inadequate or inaccurate staging. In-built
      audit in the process was followed by the introduction and implementation of
      improved guidelines. Of younger patients (15-55 years) with 'poor-risk disease',
      75% of the eligible population were entered into the appropriate randomized
      controlled trial. This intensive treatment has led to improved survival in this
      group over that which might be expected on four-drug therapy. The results of the
      randomized trial are not discussed as it is currently ongoing. This combined
      research/audit programme has resulted in greater standardization of care across a
      whole region, and confirms that the PACE (population-adjusted clinical
      epidemiology) approach facilitates the flow of information from research into
      practice and vice versa.

PMID- 9578896
TI  - The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart
      involvement.
AB  - We reviewed clinical presentation, investigations, therapy, prognosis and outcome
      of 232 patients with primary (AL) cardiac amyloidosis. There were 142 men and 90
      women. Median age at presentation was 59 years (range 29-85). AL heart disease
      was unusual both in patients under the age of 40 (3.0%) and in non-Caucasians
      (6.5%). Fatigue and weakness were the commonest presenting symptoms. Hallmark
      features of periorbital ecchymoses and macroglossia were present in 12.5% and
      27.2%, respectively. AL cardiac amyloidosis was unusual in isolation (3.9%), and
      most frequently patients had features of multiorgan dysfunction; heavy
      proteinuria and features of malabsorption predominating in this respect. Heart
      involvement represents the worst prognostic indicator, with a median survival
      from diagnosis of 1.08 years, falling to 0.75 years with the onset of heart
      failure. Current therapeutic procedures appear to prolong survival, with left
      ventricular wall thickness, mass and ejection fraction on echocardiography and
      late potentials on signal averaged electrocardiography of use in prognostic
      stratification. Cardiac involvement from AL amyloidosis is rapidly fatal. It
      should be suspected in all patients with heart failure who have wall thickening
      on echo, normal chamber sizes, low EKG voltages and evidence suggesting a
      multisystem disease.

PMID- 9578897
TI  - Immunosuppression and outcome in idiopathic membranous nephropathy.
AB  - From 1986 to 1996, 53 patients with idiopathic membranous nephropathy (IMN)
      presented to the Glasgow Royal Infirmary renal unit: 19 (36%) were treated
      because of progressive disease. We compared outcomes of treated and untreated
      patients with 37 historical and untreated controls. Five- and 10-year survival
      rates off dialysis were 83.5 and 53.5%, respectively. At the end of a mean
      observation period of 5.9 years, 47% of patients were in remission, 13% had
      reached end-stage renal failure, 15% had died, 13% had persistent proteinuria but
      stable renal function, and 11% had declining renal function. These results are
      better than those in historical controls, with a reduction in the number of
      patients reaching ESRF (13% vs. 22%), a larger proportion of patients achieving
      remission (47% vs. 30%) and smaller numbers of patients with declining renal
      function (11% vs. 19%) at the end of a similar follow-up period. These data
      suggest that the use of immunosuppression in selected patients with IMN improves
      prognosis, although the results did not achieve statistical significance.

PMID- 9578898
TI  - Cloning and ethics.

PMID- 9578899
TI  - Treating progressive and indolent MGN.

PMID- 9578900
TI  - Receptive field dimensions of lateral geniculate cells in the common marmoset
      (Callithrix jacchus).
AB  - We measured the spatial receptive field dimensions of cells in the lateral
      geniculate nucleus (LGN) of the common marmoset (Callithrix jacchus) using a
      bipartite field stimulus in which the two halves of the field were modulated
      identically but in counterphase. Horizontal and vertical edges between the two
      fields were positioned at different locations in the receptive field. By assuming
      that centers and surrounds have gaussian profiles, we were able to obtain a
      satisfactory mathematical description of the data. Receptive field centers were
      about a factor 1.6 larger than those of macaque LGN cells, in accordance with the
      smaller marmoset eye. There was a limited correspondence with dendritic tree
      dimensions of marmoset retinal ganglion cells. We further found that center and
      surround gaussians were not always concentric, and that the centers of some cells
      were elongated. This might allow some direction or orientation biases in LGN
      cells.

PMID- 9578901
TI  - Visual pigments and oil droplets from six classes of photoreceptor in the retinas
      of birds.
AB  - Microspectrophotometric examination of the retinal photoreceptors of the
      budgerigar (shell parakeet), Melopsittacus undulatus (Psittaciformes) and the
      zebra finch, Taeniopygia guttata (Passeriformes), demonstrate the presence of
      four, spectrally distinct classes of single cone that contain visual pigments
      absorbing maximally at about 565, 507, 430-445 and 360-380 nm. The three longer
      wave cone classes contain coloured oil droplets acting as long pass filters with
      cut-offs at about 570, 500-520 and 445 nm, respectively, whereas the ultraviolet
      sensitive cones contain a transparent droplet. The two species possess double
      cones in which both members contain the long-wave-sensitive visual pigment, but
      only the principal member contains an oil droplet, with cut-off at about 420 nm.
      A survey of the cones of the pigeon, Columba livia (Columbiformes), confirms the
      presence of the three longer-wave classes of single cone, but also reveals the
      presence of a fourth class containing a visual pigment with maximum absorbance at
      about 409 nm, combined with a transparent droplet. No evidence was found for a
      fifth, ultraviolet-sensitive receptor. In the chicken, Gallus gallus
      (Galliformes), the cone class with a transparent droplet contains "chicken
      violet" with maximum absorbance at about 418 nm. The rods of all four species
      contain visual pigments that are spectrally similar, with maximum absorbance
      between about 506 and 509 nm. Noticeably, in any given species, the maximum
      absorbance of the rods is spectrally very similar to the maximum absorbance of
      the middle-wavelength-sensitive cone pigments.

PMID- 9578902
TI  - 2D motion aliasing yielding 3D ambiguity. A study with variants of a Necker cube.
AB  - The 2D projection of a rotating Necker cube yields an ambiguous 3D interpretation
      based on both 2D shape and kinetic depth information. The present study shows
      that the alternation rate of the two 3D interpretations is constant with the
      rotation speed up to some critical value (around 25 turns/min for a cube whose
      sides subtend 2.5 deg) and increases monotonically thereafter. It is proposed
      that the additional perceptual reversals (PRs) observed at high rotation speeds
      are due to the increased frequency of the crossovers of the cube's edges. These
      crossovers yield 2D motion "aliasing" (or discontinuity) and "veridical" (or
      continuity) motion components. The motion aliasing (or crossover) hypothesis
      states that, in addition to the inherent ambiguity of the dynamic 2D projection
      of 3D objects, perceptual motion/perspective reversals will occur any time the
      discontinuity speed takes over the continuity speed. It is proposed that the
      relative strengths of the two components depend on the linear speed of the
      projected edges and that the discontinuity components take over the continuity
      one in the speed range where contrast sensitivity (or, above threshold,
      efficiency) is a decreasing function of speed. The motion aliasing hypothesis was
      tested and supported in a series of independent experiments showing that, for
      rotation speeds higher than 25 turns/min the PR rate increases with the crossover
      frequency at a constant speed, with linear speed at a constant crossover
      frequency and with the similarity of the crossing bars in terms of their
      orientation, polarity and spatial overlap. In addition, some of these experiments
      suggest that 2D shape and kinetic depth 3D-cues combine in such a way that the
      average PR rate they yield together is the same as the PR rate yielded by each of
      them independently. In the Discussion section we elaborate on issues related to
      the perceptual combination of ambiguous shape and kinetic depth, 3D cues.

PMID- 9578903
TI  - The influence of adaptation on perceived visual location.
AB  - We demonstrate a marked effect of prior adaptation upon the perceived position of
      subsequently presented stimuli using both first-order (luminance-defined) and
      second-order (texture-defined) stimuli. The effect of varying the contrast of the
      adapting and test stimuli depends only upon the ratio of adapting/test contrast.
      Adaptation effects for the two types of stimuli differ in terms of interocular
      transfer and rate of decay. Whilst adapting and testing with the same type of
      stimulus (first- or second-order) produces large shifts in perceived position,
      little or no crossover effect was found. The data are accounted for by a model in
      which the centroid of the linear combination of after-image and test stimulus is
      extracted.

PMID- 9578904
TI  - Speed discrimination thresholds for first--and second-order bars and edges.
AB  - Speed discrimination thresholds were measured for first- and second-order
      Gaussian bars and edges as a function of speed and the spatial scale of the
      modulation signal. Discrimination thresholds were generally higher for the second
      order patterns when compared with modulations of luminance. There were no
      systematic effects of variations in the width of the bars and edges. The results
      are discussed in relation to mechanisms for the explicit recovery of contrast
      modulations and the influence of the form of the carrier signal on visual
      performance in second-order motion tasks.

PMID- 9578905
TI  - The detection of structure in glass patterns: psychophysics and computational
      models.
AB  - Experiments are reported which examine the judgement of the mean orientation of
      textures composed either of short lines or dipoles (Glass patterns). The effects
      of element length, density, and orientation variation are described.
      Psychophysical data are compared with predictions from four schemes for
      extracting features from Glass patterns: token matching, isotropic filtering,
      oriented filtering, and "adaptive" filtering (selection of local peak output from
      multiply oriented filters). Glass patterns are spatially broadband but only
      contain orientation structure at a narrow range of scales making them suitable
      for examining how filter size is selected for texture processing. A criterion for
      scale selection is proposed: that local variation of feature orientation should
      be minimized. Simulations indicate that neither models using isotropic filtering
      nor token matching achieve human levels of performance on certain tasks. Adaptive
      filtering, operating at a scale selected using the criterion described, provides
      good agreement with the psychophysical data reported and is a practical scheme
      for deriving features using oriented filters.

PMID- 9578906
TI  - Adaptation to motion of a second-order pattern: the motion aftereffect is not a
      general result.
AB  - It has become apparent from recent work that the spatial frequency and
      orientation content of the first-order (luminance) carrier is very important in
      determining the properties of a second-order (contrast) modulation of that
      carrier. In light of this we examined whether there was any evidence for a motion
      aftereffect in one-dimensional second-order patterns containing only two
      sinusoidal luminance components: a spatial beat. The stimuli were either 1 cpd
      luminance sinusoids or 1 cpd luminance beats modulating a carrier sinusoid of 5
      cpd. The magnitude of any motion aftereffect, or any directionally specific
      effect of adaptation, was measured for all combinations of first and second-order
      test and adapting patterns. Both flickering and non-flickering stimuli were used.
      The results indicate that a motion aftereffect is only induced by first-order
      adapting stimuli, and likewise, is only measurable in first-order test stimuli.
      We find no evidence for any directionally specific effect of adaptation in second
      order stimuli, whether the test is counterphased or otherwise. These results
      apparently conflict with recent reports of a second-order induced motion
      aftereffect, but are consistent with many other findings which show differences
      between the detection of motion for first and second-order stimuli. We conclude
      that the induction of a motion aftereffect for second-order stimuli is not a
      general result and is critically dependent upon (amongst other things) the local
      properties of the stimulus, including the spatial frequency and orientation
      content of the first-order carrier.

PMID- 9578907
TI  - Cortical end-stopped perceptive fields: evidence from dichoptic and amblyopic
      studies.
AB  - Psychophysical length and width spatial interactions associated with a line
      target were measured in normal observers dichoptically and in observers with
      naturally acquired amblyopia to investigate the neural locus of end-stopped
      perceptive fields. Results show (1) interocular transfer of psychophysical end
      stopping, flank-inhibition, and length and width summation; and (2) severe, but
      significantly different, loss of end-stopping and flank-inhibition in the central
      visual fields of amblyopic eyes. Together, these results suggest a cortical basis
      for end-stopped perceptive fields, and that psychophysical end-stopping and flank
      inhibition are a consequence of distinct cortical inhibition. The damaging
      effects of amblyopia on end-stopping and flank-inhibition are weaker and less
      different from each other under transient conditions. Our results provide further
      evidence supporting the suggestion that end-stopped perceptive fields are the
      psychophysical analogs of cortical end-stopped receptive fields.

PMID- 9578908
TI  - Task-dependent changes in the shape and thickness of Listing's plane.
AB  - We examined the 2D surface formed by 3D eye positions of normal subjects to
      determine whether the shape and thickness changed in tasks that differed in
      saccadic directions: random, horizontal, vertical, radial, clockwise and counter
      clockwise. Eye positions during the random task did not lie precisely on
      Listing's plane but on a surface with a small twist. This twist was present
      before, during, and after saccades. The degree of twist changed with the task;
      becoming less twisted for horizontal tasks and more twisted in the vertical
      tasks. The surface thickness changed with the task becoming thicker for
      multidirectional tasks. This greater thickness may occur because surfaces
      obtained in multidirectional tasks are the composite of surfaces with slightly
      different shapes.

PMID- 9578909
TI  - Surface orientation from texture: isotropy or homogeneity (or both)?
AB  - We examine two models for human perception of shape from texture, based on two
      assumptions about the surface texture: isotropy and homogeneity. Observers made
      orientation judgments on planar textured surfaces. Surface textures were either
      isotropic or anisotropically stretched or compressed. If subjects used an
      isotropy assumption, they would make biased orientation estimates for the
      anisotropic textures. In some conditions some observers showed no bias for the
      anisotropic textures relative to the isotropic textures. In general, even when
      the observers showed bias, the biases were significantly less than those
      predicted if the observer used only deviation from isotropy as a cue. Observers
      appear to use both the deviation from isotropy and a texture gradient or affine
      texture distortion cue for shape from texture.

PMID- 9578910
TI  - Comparison of red-green, blue-yellow and achromatic losses in glaucoma.
AB  - Achromatic losses in glaucoma would be expected to be greater than, or equal to,
      red-green chromatic losses if the following assumptions are made: (1) the
      function of the remaining axons is either unchanged or non-selectively reduced;
      (2) red-green chromatic information is signaled by the midget ganglion cell
      system; and (3) the function of the magnocellular system is reduced at least as
      much as that of the midget ganglion cells. This prediction was tested by
      measuring red-green (along with blue-yellow) mixture thresholds for 1 deg, 0.2
      sec test spots presented on a color monitor on a white background of 50 cd/m2.
      Ellipses were fitted to plots of green contrast as a function of red contrast (or
      yellow as a function of blue), and major and minor axes of these ellipses were
      taken as measures of chromatic and achromatic thresholds, respectively. The study
      population consisted of 29 eyes in 29 patients with early glaucoma; control data
      were derived from a data bank of 83 normal eyes. Red-green losses were
      significantly (P < 0.05) greater than achromatic losses in 6 out of the 11 eyes
      which showed significant losses of either chromatic or achromatic sensitivity (or
      both). It is concluded that, for these eyes, at least one of the above three
      assumptions is incorrect.

PMID- 9578911
TI  - Cone and rod function in cone degenerations.
AB  - Progressive cone dystrophy (CD) is usually marked in the initial stages by
      reduced visual acuity, color vision deficiency and alterations in the photopic
      electroretinogram, while morphological alterations can be very mild; in some
      forms rods are affected in a later stage as well. We examined 40 patients with
      progressive cone dystrophy to determine the extent of functional losses in the
      cone system with psychophysical tests. A great variety of visual acuity and
      fundus alterations was found. Myopia was present in 74% of the patients. An
      autosomal dominant pattern of inheritance predominated (32%). No prevalence of
      gender was found. The age of onset ranged between 10 and 30 yr. All patients had
      progression of their symptoms. The total error score in color arrangement tests,
      the saturated Farnsworth Panel D-15 and the Farnsworth-Munsell 100-hue test, was
      pathologic with a predominance of confusions along the tritan and scotopic axis.
      Especially if visual acuity was below 0.5, color vision defects increased, but
      color vision defects were also found in patients with normal visual acuity. A
      general decrease of sensitivity in all three cone mechanisms was observed in
      measurements of spectral sensitivity. Moreover, cone-cone interaction as tested
      by transient tritanopia measurements was usually disturbed. In the dark
      adaptation function the threshold of the cone branch was usually elevated. These
      tests provide a good means to ascertain the correct diagnosis in early stages of
      the disease and to monitor progression in patients suffering from cone dystrophy.

PMID- 9578912
TI  - Temporal filter of the motion sensor in glaucoma.
AB  - Glaucoma reportedly affects motion perception. As an initial step in
      characterizing glaucoma-induced changes in the motion system, we determined the
      range of temporal frequencies that the motion system could process. A noise
      masking paradigm was used to measure contrast energy thresholds of 26 glaucoma
      patients at various stages of the disease and 16 age-similar subjects with normal
      vision. Using a sinusoidal stimulus, thresholds were measured for the
      discrimination of motion direction and for the stimulus embedded within a pattern
      of dynamic spatial noise. The noise was filtered to contain only low spatial
      frequencies, and the temporal-frequency spectrum of the noise was manipulated
      across conditions to derive the temporal filter shape of the most efficient
      motion sensor. The results show that the range of temporal frequencies processed
      by the motion system is diminished in the glaucoma group. The filters of the
      glaucoma subjects have reduced bandwidths compared with the normal-vision group.
      In addition, the upper cut-off frequency of the filters of the glaucoma subjects
      is correlated with stage of disease as indexed by the mean deviation of the
      Humphrey Visual Field Analyzer program 24-2, as well as the cup-to-disk ratio.

PMID- 9578913
TI  - Eosinophil count and eosinophil cationic protein concentration of induced sputum
      in the diagnosis and assessment of airway inflammation in bronchial asthma.
AB  - Measurement of eosinophil percentages and ECP concentration in induced sputum may
      be useful in the diagnosis and assessment of the variability of airway
      inflammation in bronchial asthma (BA). To evaluate the usefulness of sputum
      eosinophil counts and ECP concentrations in the diagnosis of BA, we measured
      these parameters in 68 patients with respiratory complaints. In addition, we
      followed-up 14 BA patients with variable airflow limitation for 45.4 +/- 10.4
      days. The BA group (n = 41) showed a higher percentage of sputum eosinophilia
      (24.5 +/- 7.6 vs. 2.2 +/- 2.9%, p < 0.001) and a higher level of sputum ECP
      (198.2 vs. 90.6 micrograms/L, p < 0.05) than those in the nonasthmatic group
      (NBA, n = 27). The sensitivity and specificity of sputum eosinophilia (> or = 5%)
      for the diagnosis of BA were 85.4% and 92.6%, respectively, which were better
      than the sensitivity (68.3%) and specificity (55.5%) of the increased level of
      sputum ECP (> or = 100 micrograms/L). Patients with moderate-to-severe persistent
      BA had a higher percentage of sputum eosinophil (n = 23, 34.6 +/- 10.6%) than
      those of mild persistent BA (n = 18, 10.7 +/- 5.2%, p < 0.01), but we could not
      find significant difference in ECP levels between mild persistent and moderate-to
      severe persistent asthma. The percentages of sputum eosinophilia showed a
      moderate correlation with ECP (r = 0.4358, p < 0.01) and with the peak expiratory
      flow rate (PFR, r = -0.4746, p < 0.01) but sputum ECP did not correlate with PFR.
      In 14 BA patients who were followed, there was a relationship between changes of
      PFR and the percentage of sputum eosinophil (r = -0.7238, p < 0.01), but the
      change of PFR did not correlate with the change of sputum ECP levels. These
      results suggest that the sputum eosinophil count and sputum ECP level could be
      helpful in the diagnosis of BA, but that sputum ECP is not satisfactory for the
      assessment of variability of airway eosinophilic inflammation during the initial
      anti-inflammatory management of BA.

PMID- 9578914
TI  - Serum eosinophil cationic protein (ECP) levels in patients with seasonal allergic
      rhinitis and allergic asthma.
AB  - We studied serum ECP levels in 21 seasonal allergic patients (16 patients with
      rhinitis; 5 with rhinitis and asthma) diagnosed by history, skin tests, and RAST.
      Seventeen healthy subjects were selected as a control group. None of the patients
      had received medications. Total IgE levels were also measured and correlated with
      ECP levels. Mean IgE level was found to be higher in patients than controls (p <
      0.05). Patients with asthma and rhinitis had higher IgE values than those with
      rhinitis alone (p < 0.05). Serum ECP levels in the patient group were
      significantly higher than those in the control group (p < 0.05). No statistically
      significant difference was found between ECP levels in patients with rhinitis and
      rhinitis plus asthma groups, although mean ECP was higher level in the later
      group. Total IgE and ECP levels were correlated positively in the patients (r =
      0.630, p < 0.05). We conclude that the extent of allergic inflammation in mucosal
      surfaces such as allergic rhinitis plus asthma, might influence serum ECP levels.

PMID- 9578916
TI  - Wheezing or stridor: intrinsic and extrinsic lesions causing noisy breathing.

PMID- 9578915
TI  - Eosinophil cationic protein (ECP) and tryptase in the nasal lavage fluid (NLF) of
      children with grass pollen rhinitis: levocabastine effect.
AB  - This study was carried out to determine the concentrations of eosinophil cationic
      protein (ECP) and tryptase in the nasal lavage fluid (NLF) of 24 children (C)
      with grass pollen rhinitis as well as rhinitis symptoms before and after nasal
      provocation tests with or without a levocabastine (anti-H1 topical antihistamine)
      pretreatment. All C were monosensitized to grasses only. Twelve patients (Active
      Group = AG) were tested with a nasal provocation test with grass pollen (NPT)
      carried out by the insufflation of increasingly higher doses of an allergenic
      extract powder, while the other 12 patients (Placebo Group = PG) underwent just a
      nasal provocation test with lactose (placebo) (NPTp). The prechallenge NLF,
      obtained both before (C) and after (AG) levocabastine pretreatment, was compared
      to that obtained after periods of 2 and 24 hours postchallenge. In the AG, before
      and after levocabastine pretreatment, the tryptase concentrations had not
      significantly increased, whereas the ECP concentrations were found to be
      significantly higher (p < 0.05) in just the 24-hour postchallenge samples. In the
      PG the rhinitis symptoms were not induced by the NPTp and there was no
      significant change in either ECP or tryptase concentrations. In the AG a
      levocabastine pretreatment induced a significant increase (p < 0.05) in the
      cumulative allergen doses administered by the NPT. There was a reduction of the
      nasal symptoms in 7 patients, while in 3 subjects there was only a slight
      improvement, but in 2 subjects no effect was encountered. In conclusion this
      study shows that a levocabastine pretreatment before an NPT in patients with
      grass pollen rhinitis, outside the grass pollen season, induces a significant
      increase in the cumulative allergen doses (administered by the NPT) which
      provoked rhinitis symptoms but is not able to demonstrate any significant
      reduction in the ECP concentrations of the NLF.

PMID- 9578917
TI  - Delayed occurrence of a severe cutaneous reaction in a multiple sclerosis patient
      taking interferon beta-1b.
AB  - We report a case of a patient treated for relapsing multiple sclerosis (MS) with
      interferon beta-1b who developed a severe vasculitic-like skin reaction 9 months
      after initiation of interferon therapy. Prompt discontinuation of interferon beta
      1b and institution of corticosteroid therapy was associated with complete
      resolution of the cutaneous lesions. Other potential causative agents were
      excluded by penicillin skin sensitivity testing or continuing use in the absence
      of adverse reactions. We conclude that a vasculitic-like cutaneous reaction to
      interferon beta-1b may occur long after institution of therapy in some MS
      patients. We review other case reports of severe cutaneous reactions associated
      with interferon beta-1b therapy in MS patients that suggest that susceptibility
      cofactors may be important elements in the occurrence of these reactions, and
      consider whether other medications commonly used in MS patients could have such a
      role.

PMID- 9578919
TI  - Asthma among the famous. Max Brodel (1870-1941), German-American anatomist and
      medical illustrator.

PMID- 9578918
TI  - The Jewish physician in the post-Columbus era. Supplement.

PMID- 9578920
TI  - Asthma among the famous. Arthur F. Hurst (1879-1944), British physician.

PMID- 9578921
TI  - Asthma among the famous. Robert A. Cooke (1880-1960), American physician.

PMID- 9578922
TI  - Asthma among the famous. Alban Berg (1885-1935), Austrian composer.

PMID- 9578923
TI  - The effect of nasal surgery on snoring.
AB  - Patients with nasal obstruction often have associated snoring. It is uncertain
      whether surgery, which relieves the nasal obstruction, will also relieve the
      snoring. We have reviewed 96 patients who complain of both nasal obstruction and
      snoring and who underwent nasal surgery. Snoring was completely relieved in 48
      patients (50%), was less loud in a further 38 patients (40%), unchanged in 8
      patients, and louder in 2. Patients who had nasal polypectomy as part of their
      nasal surgery obtained the greatest snoring relief. The relationship between
      nasal obstruction and snoring is complex and the alteration of airflow patterns
      after nasal surgery is postulated to be important in influencing snoring relief.
      This study suggests that, when snoring and nasal obstruction coexist, nasal
      surgery should be considered as the first line of surgical treatment.

PMID- 9578924
TI  - Cogenital bony nasal cavity deformities.
AB  - Although the most common form of nasal obstruction in neonates is soft tissue
      edema, congenital bony nasal deformities are being recognized as an important
      cause of newborn airway obstruction. In addition to the well described choanal
      atresia, CT imaging of the newborn in respiratory distress reveals two other
      forms of bony nasal cavity deformities: nasal pyriform aperture stenosis and
      nasal cavity stenosis. All of the three types of bony nasal cavity deformities
      have characteristic anatomical features, are associated with distinctive
      congenital anomalies, and are postulated to have differing embryological causes.
      Five patients with congenital bony nasal cavity deformities are presented. These
      cases illustrate the clinical and radiological presentation of varied types of
      congenital nasal cavity obstruction as well as the criteria used to guide
      clinical management.

PMID- 9578925
TI  - Is monocular perception of depth through the rigid endoscope a disadvantage
      compared to binocular vision through the operating microscope in paranasal sinus
      surgery?
AB  - Vision through the endoscope is strictly monocular. Perception of depth
      (stereopsis) during ethmoid surgery through the operating microscope would be
      expected to be superior due to binocular view. To investigate whether
      monocularity of the endoscope is a disadvantage in paranasal sinus surgery, we
      compared stereoacuity in a model of the nasal cavity using a headlamp, an
      operating microscope, and a 0 degree-Hopkins-endoscope. Twenty volunteers were
      asked to touch defined points in a spatial model of the nasal cavity. Due to the
      configuration of the model, which allowed binocular vision of all contact points
      with headlamp, performance was significantly better than with optical
      instruments. Manipulations were performed faster with the endoscope than with the
      microscope. Under microscopic guidance more faults in point sequence were made
      than with the endoscope. Various monocular phenomena obviously allow sufficient
      spatial orientation through the endoscope, so that monocularity of the endoscope
      appears not to be a disadvantage for quick and safe manipulations during
      functional endoscopic sinus surgery.

PMID- 9578926
TI  - A schematic approach to preexisting sinus disease for the immunocompromised
      individual.
AB  - Fungal rhinosinusitis is an aggressive and potentially lethal complication of
      chemotherapy and bone marrow transplant-induced neutropenia. Preexisting
      noninvasive sinusitis may be a significant risk factor in this population. An
      illustrative case is presented where preexisting noninvasive fungal sinusitis
      developed into the tissue-invasive and angio-invasive form of aspergillosis
      during chemotherapy. We propose an algorithmic approach to all patients before
      chemotherapy or bone marrow transplantation. If there is a suspicion of sinusitis
      based on a screening questionnaire, we recommend an otolaryngology consultation
      and a CT of the paranasal sinuses. Evidence of sinus disease should then be
      treated aggressively before chemotherapy or a bone marrow transplantation. Close
      posttreatment surveillance during the neutropenic phase is necessary with
      "urgent" biopsies if recurrence of disease is suspected.

PMID- 9578927
TI  - Computed tomographic measurements of the nasal sinuses and frontal bone in mummy
      heads artificially deformed in infancy.
AB  - The purpose of the present study was to ascertain whether artificial skull
      deformation, carried out during infancy, has an effect on the pneumatization of
      the frontal and maxillary sinuses and on the osseous structure of the frontal
      bone. Thus, two normal and 12 artificially deformed adult human skulls (12 males,
      two females) from the collection of pre-Columbian Peruvian skeletons and mummies
      in the Institute of Anthropology and Human Genetics (University of Munich) were
      investigated by computed tomography. These skulls had been excavated from four
      sites on the Peruvian coast: Las Trancas, Cahuachi. Pacatnamu, and Estaqueria.
      The volumes of the maxillary sinuses varied from 5.18 mL to 17.19 mL. Those of
      the frontal sinuses varied from zero to 6.21 mL. The artificial deformation of
      the skull, which occurred during infancy, had no influence on the size of the
      maxillary and frontal sinuses. There was also no difference in the average bone
      thickness of the os frontale; however, artificial deformation in infancy had an
      influence on the bone structure, resulting in a tremendous rarefication of the
      diploe of the frontal bones. Based on these findings we conclude that the various
      types of skull deformation instituted in infancy seem to exert no inhibitory
      effect on the pneumatization of either the frontal or maxillary sinuses.

PMID- 9578928
TI  - The reliability of computerized tomographic detection of the Onodi
      (Sphenoethmoid) cell.
AB  - Optic nerve injury is a devastating potential complication of endoscopic sinus
      surgery. Anatomic variations of the posterior ethmoid sinus are certainly
      contributing factors. In the most well described posterior ethmoid anatomical
      variant, the sphenoethmoid or Onodi cell, the optic nerve is placed at risk
      during sinus surgery. Improving preoperative and intraoperative identification of
      the sphenoethmoid (Onodi) cell could decrease the risk of optic nerve injury. The
      purpose of this investigation was to assess the reliability of computerized
      tomography (CT) in detecting the sphenoethmoid (Onodi) cell, and further our
      understanding of this clinically relevant anatomic variant. A total of 41
      sinonasal complexes from 21 human adult cadaveric heads were studied with a
      standard coronal and axial plane CT, and subsequent endoscopic dissection. The
      prevalence of the sphenoethmoid (Onodi) cell was determined by CT and endoscopic
      dissection, as were other anatomic characteristics of the posterior ethmoid
      anatomy. In our study, CT identified a sphenoethmoid (Onodi) cell in 3/41 (7%) of
      the sphenoethmoid complexes. However, anatomic dissection identified a
      sphenoethmoid (Onodi) cell in 16/41 (39%) complexes. Coronal orientation of the
      anterior sphenoid wall was never associated with a sphenoethmoid (Onodi) cell.
      Conversely, oblique or horizontal orientations were present in all cases of
      sphenoethmoid (Onodi) cells. Current CT scanning protocols for the paranasal
      sinuses did not reliably detect the Onodi cell. Endoscopic dissection indicates
      that the sphenoethmoid (Onodi) cell is a more frequent anatomic variant than
      previously appreciated. Awareness of anterior sphenoid wall orientation may
      assist surgeons in identifying the Onodi cell, thereby reducing the risk of optic
      nerve trauma.

PMID- 9578929
TI  - Sluder's sphenopalatine ganglion neuralgia--treatment with 88% phenol.
AB  - Patients who experience chronic recurring head and face pain present a diagnostic
      and therapeutic challenge. Treatment options for Sluder's neuralgia, an uncommon
      cause for recurring head and face pain, are controversial. We reviewed the
      outcomes of patients who underwent intranasal phenolization of the sphenopalatine
      ganglion for the treatment of Sluder's neuralgia. Eight patients were treated
      with intranasal cauterization of the sphenopalatine ganglion between 1990 and
      1995. Patients were treated an average of 13 times. Overall, patients experienced
      a 90% decrease in head and face pain for an average of 9.5 months duration.
      Interestingly, the patients described recurrent pain as less severe, less
      frequent, and of shorter duration. Intranasal phenolization of the sphenopalatine
      ganglion appears to be a safe and effective, although temporary, treatment for
      patients with Sluder's neuralgia. This article will review the symptomatology,
      differential diagnosis, and phenolization technique for treatment of Sluder's
      neuralgia.

PMID- 9578930
TI  - Immunohistochemistry of p53 in sinonasal inverted papilloma and associated
      squamous cell carcinoma.
AB  - Gene mutation of p53 is documented in head and neck cancer. No reports exist
      relating human sinonasal inverted papilloma (IP) and its transformation to
      squamous cell carcinoma (SCC). Using immunohistochemical techniques improved by
      an antigen retrieval method, p53 protein was analyzed in the following subjects:
      16 IP, 12 SCC arising in IP, and 15 SCC alone subjects. Both the intensity (PI)
      and rate (PR) of positive p53 immunostaining were evaluated using a quantitative
      AutoCAD program. We correlated p53 protein expression with clinical features. p53
      immunoreactivity is significantly lower in IP than in SCC specimens. Both the IP
      and SCC portions of IP synchronous SCC subjects showed similar p53 protein
      expression. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone.
      Alteration of p53 protein may have an important role in the early stages of IP
      malignant transformation and prove a potential biomarker for risk assessment. Low
      p53 immunoreactivity, indicating the presence of a wild-type p53, may correlate
      with the prognosis for SCC arising in IP. However, further clinical trials are
      required to investigate this possibly worthwhile prognostic marker.

PMID- 9578931
TI  - Combined intranasal ipratropium bromide and oxymetazoline in experimental
      rhinovirus infection.
AB  - The topical anticholinergic ipratropium bromide and topical decongestant
      oxymetazoline were tested to determine whether oxymetazoline alone and the
      combination were well tolerated and reduced rhinorrhea and middle ear pressure
      abnormalities during experimental rhinovirus infection. The study was double
      bind, placebo-controlled, and double dummy in design. Healthy volunteers (n =
      109) with low serum neutralizing antibody titer (< or = 1:2) were. Treatments
      inoculated with rhinovirus (type 39 or Hank's strain) and randomized to treatment
      with ipra-tropium bromide 0.06% two sprays per nostril (84 micrograms per
      treatment) and oxymetazoline 0.05% two sprays per nostril, oxymetazoline alone,
      or placebo. Treatments were self administered twice daily for 5 days beginning 1
      day after rhinovirus inoculation. The overall infection rate was 83% and of those
      infected, 88% felt that they had a cold. During the 3-hour period after dosing,
      the increase in nasal discharge was significantly lower in the combined
      ipratropium and oxymetazoline (0.13 +/- 0.17 gm/3 hr, mean +/- SE) than after
      oxymetazoline alone (0.60 +/- 0.18 gm/3 hr) or vehicle (0.73 +/- 0.18 gm/3 hr).
      Over the 5-day observation period, total daily nasal discharge also tended to be
      lower in the ipratropium plus oxymetazoline group (3.67 +/- 0.70 gm/24 hr, mean
      +/- SE) compared to oxymetazoline (5.61 +/- 0.73: 35% reduction) or the vehicle
      (5.04 +/- 0.73; 27% reduction) recipients, but the differences were not
      statistically significant. Subjective assessments of rhinorrhea indicated that
      the severity of rhinorrhea was significantly better among patients receiving
      oxymetazoline alone or with ipratropium compared to the vehicle. No significant
      difference in the cumulative frequencies of middle ear pressure abnormalities (27
      31%) were found among the treatment groups. Oxymetazoline does not consistently
      stimulate or decrease nasal mucus production, and ipratropium added to
      oxymetazoline is well tolerated and reduces rhinorrhea during experimental
      rhinovirus infection.

PMID- 9578932
TI  - Anticholinergic properties of brompheniramine, chlorpheniramine, and atropine in
      human nasal mucosa in vitro.
AB  - Brompheniramine and chlorpheniramine have anticholinergic activities, but the
      relative potency of these effects has not been well defined. The anticholinergic
      properties of brompheniramine, chlorpheniramine, and atropine were assessed in an
      in vitro model of human nasal mucosal glandular secretion. Methacholine was used
      as a cholinergic agonist to stimulate glandular secretion of 7F10-mucin. These
      drugs (0.01-1000 microM) or vehicle (saline) were added to explant cultures with
      and without 100 microM methacholine. 7F10-mucin concentrations were measured in
      culture supernatants after 2-hour incubations. The effective dose reducing
      methacholine-induced secretion (ED50) was determined. ED50 was 0.25 microM for
      atropine, 4.10 microM for brompheniramine, and 4.63 microM for chlorpheniramine.
      None of the anticholinergic drugs changed spontaneous glandular exocytosis.
      Brompheniramine and chlorpheniramine are equipotent anticholinergic agents in
      human nasal mucosa in vitro. Atropine was 16 to 19 times more potent.

PMID- 9578933
TI  - Effect of recombinant neutral endopeptidase (EC 3.4.24.11) on neuropeptide
      mediated nasal fluid secretion and plasma exudation in the rat.
AB  - The nasal mucosa harbors sensory nerves containing neuropeptides such as
      substance P (SP), which are released by capsaicin. The neuropeptides are degraded
      by peptidases, e.g., neutral endopeptidase (NEP) that is present in the nasal
      mucosa. We studied the effect of enzymatically active recombinant NEP (rNEP) on
      neuropeptide-evoked secretion of nasal fluid and plasma exudation in rats. rNEP
      administered intranasally (i.n.) reduced the capsaicin-evoked nasal fluid
      secretion but failed to reduce the secretion evoked by SP (exogenous) under the
      experimental conditions used. rNEP reduced the increase in nasal plasma exudation
      evoked by capsaicin (endogenous neuropeptides). Because rNEP reduced neuropeptide
      mediated nasal fluid secretion and plasma exudation in the rat, we suggest that
      peptidase activity in the nasal mucosa will determine the magnitude of the
      response to locally released neuropeptides.

PMID- 9578934
TI  - Enhancement of histamine--induced vascular permeability in guinea pigs infected
      with Bordetella bronchiseptica.
AB  - In the nasal mucosa, histamine induces vascular permeability, stimulates
      nociceptive nerves, and recruits parasympathetic reflexes that regulate glandular
      exocytosis. Unilateral histamine nasal provocations were performed in a group of
      guinea pigs in the prodromal stage of undiagnosed Bordetella bronchiseptica
      infection. Vascular permeability in the histamine challenged nostrils was
      increased approximately 2- to 4-fold compared to healthy animals (p < 0.001). The
      duration of significant vascular leak was prolonged from 10 to 30 minutes. In the
      contralateral, nonchallenged nostrils, secretion of total protein and albumin,
      but not exudation of intravenously infected 125I-bovine serum albumin, was
      increased, suggesting an augmentation of parasympathetic reflexes without changes
      in contralateral vascular leak. These observations suggest that Bordetella
      bronchiseptica infection leads to hyperresponsiveness to histamine in the nasal
      mucosa with increased vascular permeability and recruitment of nociceptive nerve
      parasympathetic reflexes.

PMID- 9578935
TI  - A medical librarian's progress.
AB  - The author describes how four medical librarians influenced his career and his
      values. Louise Darling, Brad Rogers, Estelle Brodman, and Bernice Hetzner became
      a professional extended family, each one contributing to different aspects of his
      career path, socialization to the profession, priorities, and principles of
      management. The lessons they imparted directly and by example are followed
      through the development of the author's career. Although the norms of the
      profession are different today, there remains a place for mentors.

PMID- 9578936
TI  - The Oral History Program: I. Personal views of health sciences librarianship and
      the Medical Library Association.
AB  - The Medical Library Association Oral History Program uses accepted oral history
      techniques to collect and preserve interviews with members. The original taped
      interviews and transcripts are kept in the Medical Library Association archives
      and made available for research purposes; edited copies of the interviews are
      distributed through the National Network of Libraries of Medicine, and members
      are encouraged to borrow and read the histories. Summaries of forty-three
      interviews provide personal views on health sciences librarianship and the
      Medical Library Association.

PMID- 9578937
TI  - Three who made an association: I. Sir William Osler, 1849-1919. II. George Milbry
      Gould, 1848-1922. III. Margaret Ridley Charlton, 1858-1931 and the founding of
      the Medical Library Association, Philadelphia, 1898.
AB  - The careers and personalities of the three founders of the Medical Library
      Association, Sir William Osler, George Milbry Gould, and Margaret Ridley Charlton
      are outlined, followed by a review of their role in the founding of the
      association. The career of Sir William Osler is well documented in existing
      literature, both in medical history and medical librarianship; the biographies of
      George Milbry Gould and Margaret Ridley Charlton are less known, and this article
      describes their lives in relation to the founding of the association. The issue
      of responsibility for the association's founding is explored, and primary
      recognition is attributed to Margaret Charlton. The author attempts to follow the
      tradition of Harvey Cushing in his The Life of Sir William Osler in allowing the
      characters to speak in their own words as much as possible.

PMID- 9578938
TI  - Past presidents I have known.
AB  - This paper is an account of the accomplishments of some of the early past
      presidents of the Medical Library Association known personally to the author in
      his career as a medical librarian. It demonstrates the qualities that made these
      librarians leaders of our profession and also indicates their personal attributes
      that contributed to the advancement of medical librarianship. It is hoped that
      the historical presentation of some of the giants of our profession will inspire
      present and future presidents and other medical librarians with an understanding
      of some of the qualities necessary to the continuing success of our profession.
      Sir William Osler, who was a great believer in libraries and librarians and
      himself a past president of MLA, summed up four qualities in his advice to
      medical students equally applicable to past and present leadership in the library
      profession--(1) the art of detachment, (2) the virtue of method, (3) the quality
      of thoroughness, and (4) the grace of humility (Osler, Sir William. Teacher and
      Student. In his Aequanimitas: with Other Addresses to Medical Students. 3d ed.
      Philadelphia, Blakiston Company, 1904. p. 27-31). It is thought that our past
      presidents possessed all of these qualities.

PMID- 9578939
TI  - Past presidents I have known.
AB  - This paper is an account of the accomplishments of some of the early past
      presidents of the Medical Library Association known personally to the author in
      his career as a medical librarian. It demonstrates the qualities that made these
      librarians leaders of our profession and also indicates their personal attributes
      that contributed to the advancement of medical librarianship. It is hoped that
      the historical presentation of some of the giants of our profession will inspire
      present and future presidents and other medical librarians with an understanding
      of some of the qualities necessary to the continuing success of our profession.

PMID- 9578940
TI  - Introduction: The Medical Library Association as an association.

PMID- 9578941
TI  - MLA's professional development program: how we took control of our future.
AB  - This article, which focuses primarily on the last fifty years, reviews the
      evolution and expansion of MLA's professional development activities. It shows
      how an integrated professional development program has emerged from a group of
      individual activities with little coordination among them. Continuing review,
      discussion, and new initiatives are needed to ensure that the membership is
      equipped with the knowledge and skills needed to function effectively in the
      twenty-first century.

PMID- 9578942
TI  - Hospital librarians and the Medical Library Association.
AB  - Hospital librarians have been active participants in and contributors to the
      Medical Library Association since it was founded. This article reviews the
      history of the Hospital Libraries Section and provides some personal observations
      on the contributions the association has made to hospital librarians and their
      growing influence on the association.

PMID- 9578943
TI  - The work of an association of medical librarians. 1898.

PMID- 9578944
TI  - The president's address. 1938.

PMID- 9578945
TI  - The Medical Library Association: aims, activities, and a brief history. 1952.

PMID- 9578946
TI  - The bright thread: the Bulletin's 75th anniversary.
AB  - This chronological review of the Bulletin of the Medical Library Association
      deals with the years 1911 through 1985. The Bulletin has had nineteen editors,
      from Marcia C. Noyes and John Ruhrah, M.D. (1911-26), through Susan Crawford,
      Ph.D. (1983-1986). This paper describes the Bulletin's gradual expansion in size
      and contents, the initiation of various departments and sections, and some of the
      pioneering articles. Major steps in expenses, income, and subscription price are
      given. Important changes in the format and the growth of the administrative and
      advisory structures are covered.

PMID- 9578947
TI  - An essay on reflection.
AB  - From the vantage point of her personal experience, the author examines milestones
      since the 1960s which have changed the medical library profession and helped
      shape the Medical Library Association. The advent of automation, including
      cataloging with OCLC and online literature searching through the SUNY Biomedical
      Communication Network, was a dramatic event that transformed the work and
      priorities of librarians, fulfilling the dreams of earlier visionaries. The
      application of technology in libraries led to an increased demand for education
      and training for librarians. The Medical Library Association responded with
      continuing education programs, and a series of important reports influenced how
      the association filled its role in professional development. Legislation
      providing federal funding, such as the Medical Library Assistance Act, resulted
      in a period of expansion for libraries and their services. The Medical Library
      Association has developed a legislative agenda to influence action in areas such
      as copyright. In the future, health sciences librarians must take a leadership
      role.

PMID- 9578949
TI  - Medical libraries in hospitals.

PMID- 9578948
TI  - Excellence, promise, vision, and values: reflections on the Janet Doe Lectures,
      1967-1997.
AB  - As the Medical Library Association prepares to enter its second century of
      service to society, it can look back with pride on the remarkable record of
      achievements of the association and its members, both personal and institutional,
      which are preserved for posterity in the Janet Doe Lectures. Established in 1966
      by an anonymous donor, the Janet Doe Lectures on the history or philosophy of
      medical librarianship trace the development of health sciences libraries and
      librarianship and the evolution of the Medical Library Association. The major
      themes which emerge from this comprehensive review of the lectures published
      between 1967 and 1997 include the changing roles and values of health sciences
      libraries and librarianship; education and credentialing of health sciences
      librarians; MLA activities and concerns; and MLA/National Library of Medicine
      relations.

PMID- 9578950
TI  - The Medical Library Association in retrospect, 1937-1967.
AB  - The medical librarian of 1967 lives in a period of changing concepts, dramatic
      new methods, everwidening scientific horizons. In looking toward the immediate
      past he may think of the medical librarian of thirty years ago as a complacent
      follower of accepted procedures, not as a pioneer in a brave new world. Yet the
      corps of trained medical librarians today and the resources of our collections
      and their management are dependent upon the efforts of those who were then
      pioneers in medical librarianship. Training, standards, recruitment, literature
      control, international relations, all had continuing attention at a time when
      financial assistance through government funds, support by administrators, concern
      by scientists was almost nonexistent. In these years the day of the devoted
      amateur passed; the trained medical librarian came into being and matured. This,
      the first Janet Doe Lecture, is named for one who illustrates the best in medical
      librarianship, serving with scholarly distinction. It is a brief survey pointing
      to some of the Association's significant achievements during the years of Miss
      Doe's greatest activity when she and her colleagues met their "Challenge of
      Change".

PMID- 9578951
TI  - Celebrating the past; anticipating a bright future.

PMID- 9578952
TI  - Efficiency, stability, recognition, resolution.

PMID- 9578953
TI  - Rachael Keller Anderson Medical Library Association president 1997-1998.

PMID- 9578954
TI  - Recommendations for the fitness assessment, programming, and counselling of
      persons with a disability.

PMID- 9578955
TI  - Musculoskeletal and neurological disabilities: implications for fitness
      appraisal, programming, and counselling.

PMID- 9578956
TI  - Considerations for fitness appraisal, programming, and counselling of individuals
      with sensory impairments.
AB  - Providing active living opportunities to all individuals, including people with
      disabilities, requires supporting each person's ability to participate.
      Successful inclusion often occurs, despite antiquated, inaccessible facilities,
      when everyone--leaders and participants alike--believes that each person has an
      equal right to participate, and programmes are offered that suit the varied
      interests and abilities of all participants.

PMID- 9578957
TI  - Considerations for fitness appraisal, programming, and counselling of people with
      intellectual disabilities.

PMID- 9578958
TI  - Vesico-ureteral reflux: a genetic condition?
AB  - Vesico-ureteral reflux (VUR) is a frequent condition, but in most instances, the
      precise cause is unknown. We here review the evidence of a genetic aetiology of
      VUR, inherited as an autosomal dominant trait, with variable expression. We
      discuss the possible pathogenetic relationship between VUR and other types of
      uropathies and possible strategies towards the identification of genes underlying
      VUR are presented. The isolation of the gene(s) responsible for uropathies will
      not only lead to a better insight into the embryology of the urological system,
      the pathogenesis of uropathies, but also to a renewed interest from clinicians in
      congenital uropathies.

PMID- 9578959
TI  - De novo mutations of the growth hormone gene: an important cause of congenital
      isolated growth hormone deficiency?
AB  - A family with isolated growth hormone deficiency (IGHD) in two children and their
      mother is reported. Genetic analysis revealed a heterozygous splice site mutation
      in intron III of the GH-1 gene. This mutation was de novo in the mother and was
      transmitted in a dominant way to her offspring. CONCLUSION: De novo mutations in
      the GH-1 gene may be an important cause of congenital idiopathic IGHD. As these
      patients have normal fertility, pointing out this mutation is of great value for
      appropriate genetic counselling in patients with idiopathic IGHD.

PMID- 9578960
TI  - Predominance of large low density lipoprotein particles and lower fractional
      esterification rate of cholesterol in high density lipoprotein in children with
      insulin-dependent diabetes mellitus.
AB  - Coronary artery disease (CAD) is a major cause of death in patients with insulin
      dependent diabetes mellitus. Qualitative changes in low density lipoprotein (LDL)
      and high density lipoprotein (HDL) are thought to be important for evaluating the
      risk for CAD. In the present study, we evaluated LDL particle size (LDL-size) by
      2%-16% gradient gel electrophoresis, along with conventional lipids and
      apolipoproteins, in 23 children with IDDM (10 males and 13 females) and 27
      nondiabetic controls (12 males and 15 females). The fractional and molar
      esterification rates (FER and MER) of cholesterol in plasma and HDL were also
      determined. Plasma levels of triglyceride were significantly lower in diabetic
      children than in controls. Plasma apoA-I and apoA-II levels in female diabetic
      children were significantly higher and lower than those in controls respectively.
      Plasma levels of HDL-cholesterol and the ratio of apoA-I to apoA-II were
      significantly higher in diabetic children than in controls. Other lipid and
      apolipoprotein parameters in diabetic children were similar to those in controls.
      LDL-size in diabetic children was significantly greater than that in controls.
      FERHDL, which reflects the particle size distribution of HDL, was significantly
      lower in diabetic children than in controls, which suggests that diabetic
      children had larger HDL particles. CONCLUSION: The qualitative and quantitative
      changes in LDL and HDL in diabetic children are similar to those associated with
      a reduced risk for CAD. Intensive insulin therapy in children may help preventing
      coronary heart disease in adulthood.

PMID- 9578961
TI  - Faecal immunoreactive lipase: a simple diagnostic test for cystic fibrosis.
AB  - The study evaluates faecal immunoreactive lipase (IRL) measurement in spot stool
      samples as an index of exocrine pancreatic function in patients with cystic
      fibrosis (CF). Stool samples (211) from 183 healthy volunteers (age range: 2 days
      14.2 years) showed a normal log distribution of IRL values with a median
      concentration of 71.4 micrograms/g (range: 0.53-4160 micrograms/g). In 156 stool
      samples from 58 patients with proven CF, the median IRL concentration of 0.4
      microgram/g (range: 0.003-107 micrograms/g) was significantly lower (P < 0.001)
      than that of normal controls. In healthy controls, IRL levels were age related
      with significantly higher levels (P < 0.001) shortly after birth compared to
      older children. Stimulation of the exocrine pancreas by oral milk feeding
      resulted in a significant (P < 0.001) increase in a faecal IRL concentration.
      Faecal IRL concentrations in meconium were very low and of the same magnitude as
      in patients with CF. CONCLUSION: Faecal IRL determination had a high diagnostic
      sensitivity (87%) and excellent diagnostic specificity (97%) in patients with CF.
      A negative test result (PVneg. 99%) virtually excluded CF under screening
      conditions.

PMID- 9578962
TI  - Congenital absence of the portal vein associated with focal nodular hyperplasia
      of the liver and cystic dysplasia of the kidney.
AB  - Congenital absence of portal vein is a rare malformation. To date, 16 cases have
      been reported--all in association with other anomalies, i.e. benign or malignant
      hepatic neoplasms in 6 cases and cardiac malformations in 12. This case report
      described a girl with congenital absence of portal vein, focal nodular
      hyperplasia of the liver and cystic kidney dysplasia. Angiography showed the
      splenic vein and superior mesenteric vein joining to form a common trunk that
      entered the inferior vena cava directly above the liver. A review of the other
      cases in the literature is provided and the clinical aspects of our patient are
      discussed.

PMID- 9578963
TI  - Epstein-Barr virus DNA in the cerebrospinal fluid of an HIV patient with primary
      cerebral lymphoma.
AB  - The case of a 7-month-old boy with vertically acquired immunodeficiency syndrome
      and multifocal primary cerebral lymphoma is reported. Neither neurological nor
      neuroradiological findings contributed towards the appropriate diagnosis.
      Positive Epstein-Barr virus DNA, assessed by means of polymerase chain reaction
      in cerebrospinal fluid, strongly suggested a diagnosis of primary cerebral
      lymphoma, which was subsequently confirmed by autopsy. CONCLUSIONS: The detection
      of Epstein-Barr virus DNA using the polymerase chain reaction in cerebrospinal
      fluid is useful for the diagnosis of primary cerebral lymphoma.

PMID- 9578964
TI  - Differential diagnosis of neonatal adrenal haemorrhage and congenital
      neuroblastoma by colour coded Doppler sonography and power Doppler sonography.
AB  - The differentiation between neonatal neuroblastoma and adrenal haemorrhage may be
      very difficult in the individual case. We investigated eight neonates with
      adrenal haemorrhage and one patient with congenital neuroblastoma by colour coded
      Doppler sonography and power Doppler sonography. Six haemorrhages were cystic,
      whereas the neuroblastoma and four adrenal haemorrhages had a solid appearance.
      Colour coded Doppler sonography and power Doppler demonstrated vessels within the
      neuroblastoma. In none of the ten adrenal haemorrhages could flow be shown either
      with conventional colour coded Doppler sonography or power Doppler sonography.
      CONCLUSION: Conventional colour coded Doppler sonography and power Doppler
      sonography are useful to differentiate between neuroblastoma and adrenal
      haemorrhage.

PMID- 9578965
TI  - Serum levels of phospholipid fatty acids in mothers and their babies in relation
      to allergic disease.
AB  - The fatty acid composition of serum phospholipids was analysed by gas
      chromatography in 26 non-allergic and 32 allergic mothers at the time of
      delivery. In 47 of them the levels were compared with those in the cord blood of
      their babies. The children were then followed for 6 years with regard to the
      development of allergic disease. There was an inverse relationship between the
      levels of linoleic acid (LA, C18:2n-6) and its metabolic products arachidonic
      acid (AA, C20:4n-6) (r = -0.63, P < 0.001), and C22:4 (r = -0.50, P < 0.01) in
      the non-allergic, but not in allergic mothers (r = 0.25 and r = -0.39,
      respectively). Comparing the fatty acid levels in maternal and umbilical cord
      serum, a significant correlation was observed between the LA levels in serum of
      non-allergic mothers and their babies (r = 0.53, P < 0.05). Furthermore, the
      maternal dihomo-gamma-linolenic acid (DHGLA, C20:3n-6) levels correlated with the
      cord serum levels of AA (r = 0.65, P < 0.01) and C22:4 (r = 0.65, P < 0.01) and
      with docosahexaenoic acid (DHA, C22:6n-3, r = 0.65, P < 0.01). None of these
      relationships were seen when comparing the fatty acid levels in the allergic
      mothers and their babies. In the mothers of children who did not develop any
      allergic manifestations during the first 6 years of life, the AA levels
      correlated with C22:4 (r = 0.53, P < 0.001) and eicosapentaenoic acid (EPA,
      C20:5n-3) (r = 0.56, P < 0.001). Similar findings were recorded within the n-3
      series of fatty acids, i.e. the levels of docosapentaenoic acid (DPA, C22:5n-3)
      correlated with DHA (r = 0.61, P < 0.001). None of these correlations were
      significant in the 20 mothers whose babies developed allergic disease (r = 0.42,
      0.28 and 0.44 respectively). Taken together, the findings indicate that there is
      an abnormal metabolism relationship between some of the long-chain
      polyunsaturated fatty acids in allergic mothers, affecting their infants.
      Furthermore, the findings suggest an association between the fatty acid
      composition in maternal serum and the appearance of allergic disease in their
      children during the first 6 years of life. CONCLUSION: The proportions of various
      long-chain polyunsaturated fatty acids were altered in the serum phospholipids of
      allergic pregnant mothers and in mothers whose babies developed allergic disease
      over the first 6 years of life, indicating that atopy is associated with a
      disturbed fatty acid metabolism.

PMID- 9578966
TI  - Diagnosis of paediatric Lyme arthritis using a clinical score.
AB  - Diagnosis of Lyme arthritis (LA) in children and adolescents may be difficult due
      to non-specific clinical manifestations and unreliable serological tests for
      antibodies to Borrelia burgdorferi. In a national prospective study, 186 children
      with arthritis were examined in whom the attending physicians had considered the
      diagnosis of LA. Ultimately, LA was confirmed in 87 patients and these were
      compared with the remaining 99 children in whom arthritis was attributable to
      other causes. In comparison to patients with other causes of arthritis, patients
      with LA had a higher frequency of episodic arthritis and initial knee joint
      arthritis, reported tick bites more frequently, were older, had a lower frequency
      of initial arthralgias, and there were fewer large joints involved. A score was
      developed in a group of these patients and tested in a second group. It enabled
      patients with LA to be distinguished from those with other causes of arthritis:
      within a range from 12 to -7 points, a score of 2.5 or less excluded LA whereas 6
      or more points were highly indicative of LA. If only those children with a score
      result between 2.5 and 6 had been tested for antibodies to B. burgdorferi, the
      number of tests would have been reduced by 63%. CONCLUSION: Careful analysis of
      clinical presentation and use of a clinical score may help in distinguishing LA
      from other causes of arthritis and thus reduce unnecessary and expensive testing
      and uninterpretable test results.

PMID- 9578967
TI  - Manoeuvres to elevate mean airway pressure, effects on blood gases and lung
      function in children with and without pulmonary pathology.
AB  - During mechanical ventilation, mean airway pressure (MAP) can be increased by a
      variety of manoeuvres, for example increasing inspiratory time or elevating the
      positive end expiratory pressure (PEEP). It seemed likely that the effect on
      blood gases and lung function of a particular manoeuvre to increase MAP would be
      influenced by the presence of respiratory pathology and thus the manoeuvre best
      at improving respiratory status in children with an abnormal chest radiograph
      appearance would differ from that most efficacious in children without such a
      problem. The aim of this study was to test that hypothesis. Twenty-two children,
      median age 15 months (range 2.5 weeks-10 years) were examined. Group 1 (n = 10)
      had no chest radiograph abnormalities and group 2 (n = 12) lobar collapse and/or
      consolidation. The patients were studied at baseline settings and at an elevated
      MAP resulting from (in random order) an increase in inspiratory time (T1),
      pressure PEEP or peak inspiratory pressure (PIP). In group 1, elevating PIP
      improved oxygenation and carbon dioxide elimination (P < 0.01) and prolonging T1
      improved oxygenation (P < 0.05). In group 2, only raising PEEP significantly
      improved oxygenation (P < 0.01), but this was associated with carbon dioxide
      retention (P < 0.01). CONCLUSION: The presence of lung pathology does influence
      which manoeuvre should be used to elevate MAP to improve blood gases in the
      paediatric population.

PMID- 9578968
TI  - Treatment and follow-up of children with cerebrotendinous xanthomatosis.
AB  - The clinical spectrum and the effects of treatment over a period of 5 years in
      five children with cerebrotendinous xanthomatosis (CTX) are described. In all
      children biochemical, neuroradiological, and neurophysiological studies were
      done. CTX was diagnosed and effects of therapy were evaluated by determination of
      the serum cholestanol/cholesterol ratio (CCR) and the urinary excretion of bile
      alcohols. All children were treated with chenodeoxycholic acid (15 mg/kg/day) in
      three divided oral doses. Diarrhoea and juvenile cataract were the main clinical
      features. Psychomotor retardation, pyramidal and cerebellar signs were also
      found. After starting treatment, biochemical abnormalities normalized and
      diarrhoea disappeared. After 1 year of therapy there was no further delay in
      motor development, and in three children the intelligence quotient improved. EEG
      abnormalities disappeared. After 5 years of therapy the children are in a stable
      clinical condition. CONCLUSION: The clinical, biochemical and neurophysiological
      abnormalities in five children with CTX showed a remarkable improvement after
      starting treatment with chenodeoxycholic acid. The early diagnosis of CTX and the
      start of treatment with chenodeoxycholic acid has prevented neurological
      deterioration for a period of 5 years.

PMID- 9578970
TI  - Low birth weight at term impairs cord serum lipoprotein compositions and
      concentrations.
AB  - The purpose of this study was to determine the effect of low birth weight at term
      on serum lipoproteins. Lipid and apolipoprotein (apo) contents were investigated
      in cord sera of small-for-gestational-age (SGA) newborns at term (2290 g +/- 33
      g) and compared with those of appropriate-for-gestational-age (AGA) newborns
      (3570 g +/- 93 g). In SGA newborns, VLDL amounts were twofold higher, whereas
      LDL, HDL2 and HDL3 contents were lower than in AGA newborns (-38%, -44% and -42%,
      respectively). VLDL-triacylglycerols (TG), apo B-100 and apo E were higher, while
      VLDL-apo C-II values were 39% lower in SGA newborns compared with those of AGA
      newborns. In SGA newborns, HDL2-apolipoprotein, phospholipid and cholesteryl
      ester levels were respectively reduced to 70%, 50% and 40% compared with AGA
      values. HDL3-apolipoprotein and phospholipid contents were also decreased in SGA
      newborns (-43% and -60%, respectively). The different HDL2 and HDL3
      apolipoproteins (apo A-I, A-II, C-III and E) were significantly decreased in SGA
      newborns. CONCLUSION: Intra-uterine growth retardation was accompanied by
      alterations in apolipoproteins and lipid compositions in the four lipoprotein
      fractions, which may impair lipid metabolism. Follow up studies on lipoprotein
      patterns in SGA infants are required to investigate whether such abnormalities at
      birth lead to diseases in adulthood.

PMID- 9578969
TI  - Mild or absent clinical signs in twin sisters with short-chain acyl-CoA
      dehydrogenase deficiency.
AB  - Two HLA-identical twin sisters are reported, of whom one has remained essentially
      asymptomatic, and an episode of hypotonia and decreased level of conciousness
      being the only relevant clinical finding in the other. Organic acid-analysis
      revealed that ethylmalonate was constantly, although sometimes only slightly,
      increased. No abnormal acylglycines or acylcarnitines could be detected. Enzyme
      assay in cultured skin fibroblasts confirmed short-chain acyl-CoA dehydrogenase
      deficiency. CONCLUSION: The lack of appropriate biochemical markers for this
      deficiency makes the diagnosis difficult and consequently, the low number of
      patients described may be the result of underdiagnosis.

PMID- 9578971
TI  - Thrombomodulin serum levels in ventilated preterm babies with respiratory
      distress syndrome.
AB  - A soluble form of thrombomodulin (TM), an anticoagulant proteoglycan of the
      endothelial cell membrane, considered a marker of vascular endothelial damage,
      was measured in plasma of preterm infants with respiratory distress syndrome
      (RDS). In these patients, lung immaturity leads to endothelial leak of plasma
      proteins and to surfactant inhibition. In 18 babies with RDS, plasma TM
      concentration was significantly elevated compared with values of a matched group
      of babies without pulmonary disease (276.1 ng/ml vs 141.3 ng/ml) (P < 0.05).
      Furthermore, TM levels of mechanical ventilated babies (IPPV) with severe RDS
      were higher than those of babies with moderate RDS and treated with nasal CPAP
      (340.9 ng/ml vs 174.2 ng/ml) (P < 0.05). CONCLUSION: These data show that TM can
      be used as marker of pulmonary endothelial damage in preterm babies treated with
      mechanical ventilation for RDS and suggest early intervention with exogenous
      surfactant to limit alveolar protein leakage and surfactant inactivation.

PMID- 9578972
TI  - Risk factors for respiratory syncytial virus associated apnoea.
AB  - Respiratory syncytial virus (RSV) infections are characterized by upper or lower
      respiratory tract symptoms including bronchiolitis and pneumonia. Apnoea may be
      the first sign of disease in children with RSV infection. The aims of this study
      were the identification of independent risk factors for RSV associated apnoea and
      the prediction of the risk for mechanical ventilation in children with RSV
      associated apnoea. Medical records of children younger than 12 months of age
      admitted with RSV infection between 1992 and 1995 to the Sophia Children's
      Hospital, were reviewed. Demographic parameters, clinical features and laboratory
      parameters (SaO2, pCO2 and pH) were obtained upon admission and during
      hospitalization. Children with and without apnoea were compared using univariate
      and multivariate logistic and linear regression analysis. One hundred and eighty
      five patients with RSV infection were admitted of whom 38 (21%) presented with
      apnoea. Patients with apnoea were significantly younger, had a significantly
      lower temperature, higher pCO2 and lower pH and had on chest radiographs also
      more signs of atelectasis. The number of patients admitted to the ICU because of
      mechanical ventilation and oxygen administration was significantly higher in
      children with RSV associated apnoea. Apnoea at admission was a strong predictor
      for recurrent apnoea. The relative risk for mechanical ventilation increased with
      the number of episodes of apnoea: 2.4 (95% CI 0.8-6.6) in children with one
      episode of apnoea (at admission) versus 6.5 (95% CI 3.3-12.9) in children with
      recurrent episodes of apnoea. CONCLUSIONS: Age below 2 months is the strongest
      independent risk factor for RSV associated apnoea. Apnoea at admission increases
      the risk for recurrent apnoea. The risk for mechanical ventilation significantly
      increases in children who suffer from recurrent apnoea.

PMID- 9578973
TI  - Lung volume measurements in infants with and without chronic lung disease.
AB  - Infants born prematurely who develop chronic lung disease (CLD) have airways
      obstruction and hence may have low lung volume. The aim of this study was to test
      that hypothesis and ascertain whether the nature of the comparison control group
      influenced the results. Sixteen infants who were oxygen dependent for more than
      28 days (CLD) and eight infants without CLD had measurements of functional
      residual capacity (FRC) at 14 and 28 days. The 16 CLD infants consisted of eight
      less than 27 weeks gestational age (group A) and eight greater than 26 weeks
      gestational age (group B). The eight infants without CLD (group C) were each
      matched for gestational age and gender to infants in group B. Group A compared to
      group C had lower FRCs both at 14 days (median 18 ml/kg vs 27 ml/kg, P < 0.01)
      and 28 days (median 20 ml/kg vs 26 ml/kg, P < 0.05), but group A differed from
      group C with respect to both gestational age (P < 0.01) and birth weight (P <
      0.01). The FRC results of group B were lower than those of their matched controls
      (group C) only at 28 days (median 22 vs 26 ml/kg, P < 0.05). Overall, the FRC
      results at 14 and 28 days correlated significantly with the duration of oxygen
      and ventilator dependence and weakly with gestational age. CONCLUSION: These
      results support the hypothesis that FRC results are lower in infants with CLD
      compared to those without CLD when measured in the neonatal period and emphasize
      the importance of an appropriate control group. Measurement of lung volume may
      facilitate assessment of the response to therapies for CLD.

PMID- 9578974
TI  - Prediction of febrile seizures in siblings: a practical approach.
AB  - To quantify the risk of febrile seizures (FS) in relatives of children with FS
      and to predict the risk of FS in siblings, we calculated cumulative risks of FS
      in first degree relatives of 129 children with FS. The study was conducted as a
      prospective follow up study of FS recurrences at the outpatient clinic of the
      Sophia Children's Hospital in Rotterdam. Thirteen parents and 12 siblings had
      experienced FS, accounting for a 6-year cumulative risk of 7%. The risk of FS was
      increased in relatives of children with recurrent FS (12%). The risk of FS in
      siblings (10%) in our study was more than twice the average risk in a similar
      population (4%). A positive FS history in a parent, young age at onset in the
      proband, and recurrences in the proband were selected in a multivariable
      prediction model. If two or more of these risk factors were present, the risk of
      West European siblings to develop FS was 46% (hazard ratio 5.4). CONCLUSION: The
      cumulative risk of FS in siblings of children with FS is increased. The age
      attained risk of FS can be estimated using a practical model incorporating three
      readily available risk factors.

PMID- 9578975
TI  - A boy with therapy-resistant asthma.

PMID- 9578976
TI  - Severe hypoglycaemia in diabetic children and adolescents.

PMID- 9578977
TI  - Dextromethorphan in a child with nonketotic hyperglycinaemia--a 6-year follow up.

PMID- 9578978
TI  - Myelodysplastic syndrome with signs of auto-immune disease in a patient with
      renal allograft.

PMID- 9578979
TI  - Ureteral obstruction in a patient with chronic granulomatous disease, receiving
      combined prophylaxis with IFN-gamma and antibiotics.

PMID- 9578980
TI  - Traditional view empirically revisited: normal intellectual functioning in breath
      holding spells.

PMID- 9578981
TI  - Phylogeny of the cholecystokinin/gastrin family.
AB  - The neuroendocrine peptides cholecystokinin (CCK) and gastrin, originally
      identified in mammals, are characterized by a common amidated C-terminal
      tetrapeptide sequence, Trp-Met-Asp-Phe.NH2, which also constitutes the minimal
      structure necessary for biological activity of both. Hence, it has been proposed
      that CCK and gastrin have evolved from a common ancestor. Although the occurrence
      of CCK/gastrin-related peptides has been suggested in representatives of several
      invertebrate phyla, the evidence, mostly based on immunoreactivity, has not been
      substantiated by peptide identification. Instead, CCK/gastrin-specific antibodies
      might be cross-reacting with Asp-Phe-amides, like the lymnaDFamides, isolated
      from the freshwater snail Lymnaea stagnalis. Cionin, isolated from Ciona
      intestinalis, a representative of the protochordates that occupy a key position
      at the transition to vertebrates, so far represents the oldest genuine member of
      the CCK/gastrin family, dating the emergence of these peptides back to at least
      500 million years ago. The CCK/gastrin family appears to be represented in the
      whole chordate phylum, and in addition to mammals, CCK and gastrin have recently
      been identified in a number of nonmammalian species representing the major
      vertebrate classes, including fishes, amphibians, reptiles, and birds. This now
      makes it possible to consider the CCK/gastrin phylogeny based on structural
      information. A duplication of the ancestral gene appears to have already occurred
      before or during the appearance of cartilaginous fish, giving rise to two
      peptides most likely homologous to mammalian CCK and gastrin. Indicative of a
      function of gastrin, the acid secretory system appears to have developed
      concomitantly in sharks. The segregation of CCK and gastrin early in vertebrate
      evolution resembles the situation in other peptide families, in accordance with a
      suggested widespread pattern of multiplication within vertebrate peptide and
      protein families around 400 million years ago. At the amphibian level, two
      separate peptide systems, resembling mammalian CCK and gastrin, have been
      characterized by identification of the mature bioactive peptides, cDNAs, gene
      structures, primary and secondary sites of gene expression, and their
      physiological actions. The overall gene structure, including exon/intron
      organization, is similar in all mammalian and nonmammalian CCK/gastrin genes. CCK
      is well conserved in all vertebrate species investigated, while the mammalian
      gastrins at first sight appear as a distinct group with little similarity to the
      nonmammalian gastrins outside the invariant C-terminal tetrapeptide and the C
      terminal flanking peptide of the prohormone. However, evidence indicates that the
      transition from nonmammalian to mammalian gastrin may not be as dramatic as first
      anticipated. In conclusion, the CCK/gastrin family appears to be represented in
      most, if not all, chordates, to which group it may also be limited. The two major
      classes, CCK and gastrin, probably arose as distinct peptide systems early in
      vertebrate history. While CCK is well conserved in all vertebrates, a major
      structural change of gastrin accompanied the transition to mammals.

PMID- 9578982
TI  - Proadrenomedullin-derived peptides.
AB  - Posttranslational processing of the adrenomedullin gene product results in the
      formation of at least two biologically active peptides, adrenomedullin (AM) and
      proadrenomedullin N-20 terminal peptide (PAMP). Produced predominantly in the
      vasculature, both peptides are potent hypotensive agents, albeit via unique
      mechanisms of action. The gene is transcribed in a variety of other tissues
      including brain, pituitary, and kidney. Numerous actions have been reported most
      related to the physiologic control of fluid and electrolyte homeostasis. In the
      kidney, AM is diuretic and natriuretic, and both AM and PAMP inhibit aldosterone
      secretion by direct adrenal actions. In pituitary gland, both peptides at
      physiologically relevant doses inhibit basal ACTH secretion, again by apparently
      differing mechanisms. Additionally, AM antagonizes CRH-stimulated ACTH release.
      The peptides are produced in numerous brain sites, including hypothalamus and
      brainstem. Inhibition of AVP release has been reported and the physiologic
      significance of AM's ability to inhibit water drinking and salt appetite has been
      established. Thus the peptides appear to act in brain and pituitary gland to
      facilitate the loss of plasma volume, actions which complement their hypotensive
      effects in the blood vessel. Interestingly, direct cardiac effects (positive
      inotropism and chronotropism) and CNS actions (sympathostimulation) have been
      reported, leading to the hypothesis that these peptides also can exert important
      cardioprotective effects, helping to prevent vascular collapse during states of
      high AM secretion such as sepsis.

PMID- 9578983
TI  - Nerve growth factor in pituitary development and pituitary tumors.
AB  - Cells in the anterior pituitary originate from a common pluripotent precursor
      whose phenotypic development is determined by intrapituitary transcription
      factors as well as by hypothalamic and peripheral signals. A rapidly growing body
      of evidence revealed that essential to the differentiation and proliferation of
      pituitary cells are an array of growth factors that are produced within the
      pituitary and act mainly through autocrine mechanisms. Growth factors are
      polypeptides that are released in carefully measured amounts by some cells to
      regulate cell growth and differentiation by activating specific tyrosine kinase
      receptors in the plasma membrane of target cells. Both overproduction of
      mitogenic growth factors and loss of factors inhibiting cell proliferation result
      in uncontrolled cell growth and tumor development. There is now increasing
      evidence that disruption of the calibrated signalling network activated by
      pituitary growth factors plays a central role in pituitary tumorigenesis. This
      paper is focussed on the role of nerve growth factor (NGF) in pituitary
      physiology and pathology. In particular, we propose that NGF plays a dual role in
      the gland: a local one as a stimulator of differentiation and proliferation of
      lactotrope cells during pituitary development and a systemic one as a
      neurohormone which is cosecreted with prolactin into the bloodstream.
      Furthermore, we discuss the evidence that NGF is an autocrine differentiation
      factor for prolactin-secreting cells. Escape from NGF control appears to be one
      of the mechanisms involved in the development and progression of prolactinomas.
      Along the same line, exposure of prolactinomas refractory to dopaminergic therapy
      to exogenous NGF results in their differentiation into lactotrope-like cells
      reexpressing the D2 receptor protein. This observation may open the way to a
      sequential therapy with NGF and bromocriptine for patients refractory to the
      conventional therapy.

PMID- 9578984
TI  - Prevention of cancer and cardiovascular diseases: a common strategy?
AB  - Cancer and cardiovascular diseases are two pathological states involving
      uncontrolled proliferation of either tumor or vascular smooth muscle cells.
      Interestingly, both types of disease can be prevented by the same type of
      chemical agent, such as marine polyunsaturated fatty acids, sulfur-containing
      compounds present in garlic, and wine polyphenols, among others, which seem to be
      fairly effective in the prevention of certain types of cancer and cardiovascular
      diseases. This is supported by numerous epidemiological studies and laboratory
      experiments involving animal models. It is therefore suggested that the mode of
      action of these compounds interfering with the development of these pathological
      states share some common trends. This could be taken into consideration in future
      studies related to the molecular mechanisms leading to these diseases as well as
      with the chemopreventive potential of some dietary components.

PMID- 9578985
TI  - The search for orally active medications through combinatorial chemistry.
AB  - The literature of combinatorial chemistry is reviewed with particular attention
      paid to considerations of absorption, distribution, metabolism and excretion in
      the design and evaluation of libraries containing drug-like molecules. Published
      libraries are evaluated in particular for the likelihood that the products would
      possess oral bioavailability.

PMID- 9578986
TI  - Relationships between stress, protein damage, nutrition, and age-related eye
      diseases.

PMID- 9578987
TI  - Predictors of state legislators' intentions to vote for cigarette tax increases.
AB  - BACKGROUND: This study analyzed influences on state legislators' decisions about
      cigarette tax increase votes using a research strategy based on political science
      and social-psychological models. METHODS: Legislators from three states
      representing a spectrum of tobacco interests participated in personal interviews
      concerned with tobacco control legislation (n = 444). Measures of potential
      predictors of voting intention were based on the consensus model of legislative
      decision-making and the theory of planned behavior. Multiple logistic regression
      methods were used to identify social-psychological and other predictors of
      intention to vote for cigarette tax increases. RESULTS: General attitudes and
      norms concerning cigarette tax increases predicted legislators' intention to vote
      for cigarette tax increases. More specific predictors included perceptions of
      public health impact and retail sales impact of cigarette tax increases.
      Constituent pressure was the strongest perceived social influence. Political
      party and state also were strong predictors of intention. Results were consistent
      with related research based on political science models. CONCLUSIONS:
      Legislators' votes on cigarette tax increases may be influenced by their
      perceptions of positive and negative outcomes of a cigarette tax increase and by
      perceived constituent pressures. This research model provides useful insights for
      theory and practice and should be refined in future tobacco control research.

PMID- 9578988
TI  - Introduction to the report on the conference on the "critical" period of brain
      development.

PMID- 9578989
TI  - How a child builds its brain: some lessons from animal studies of neural
      plasticity.
AB  - Although the potential vulnerability of children's brain development is generally
      recognized, relatively little is known about the timing, resiliency, or
      mechanisms involved. While animal research should be applied only cautiously to
      human policy, some findings do have important clinical implications. This paper
      briefly reviews animal studies demonstrating the effects of experience on brain
      structure. Contemporary theories emphasize the self-organizing potential of brain
      structure, particularly regions that seem to have evolved for the purpose of
      storing information. We emphasize three major findings: (1) many regions of the
      brain are responsive to experience, but they differ in the types of information
      stored and in their developmental timing. (2) One type of plasticity is typically
      embedded in a developmental program, and it requires appropriate timing and
      quality of the information stored for the animal's development to be normal. (3)
      Another category of plasticity stores information that is idiosyncratic and
      unpredictable, but is often useful for species such as humans that learn
      throughout their life span. We therefore expect that some aspects of human brain
      development use the first type of plasticity and that abnormal experience or
      deprivation may cause lasting harm to brain and behavior. However, because the
      other type of plasticity lasts a lifetime, efforts such as psychotherapy or
      social interventions may help heal a wounded brain.

PMID- 9578990
TI  - The nature of early memory.
AB  - Despite tremendous gains in our understanding of the development of memory during
      the infancy period, relatively little is known about the neural bases of early
      memory. This is unfortunate, as elucidating the neurobiological mechanisms that
      mediate changes in memory would likely yield important insight into the concept
      of infantile amnesia, that is, the inability to recall those events that occur
      during the first 3-4 years of life. This paper begins by describing the major
      types of memory adults are capable of and the corresponding neural substrate of
      each type. A brief exposition of the neural bases of memory development is then
      provided, including a description of recent work that examines long-term memory
      in infancy. It is concluded that maturation of cortical areas in the temporal and
      frontal cortices that transpires between the ages of 1 and 4 years likely
      accounts for our lack of access to our earliest memories. It is also argued that
      the examination of the electrophysiological correlates of memory development may
      shed light on these cortical changes.

PMID- 9578991
TI  - The critical impact of early cellular environment on neuronal development.
AB  - Normal brain development requires the precise interactions of environmental
      signals with genes that drive cellular differentiation and circuit formation.
      Experimental studies in animal models reveal that early environmental influences
      in utero can modulate cell fate choice and neuronal growth. Modification of the
      determinants can have long-lasting consequences. Studies using transplant and
      cell culture methods have examined the development of the limbic system, regions
      of the brain that mediate cognition, emotion, memory, and learning. The results
      show that growth factors in the environment of progenitor cells control long-term
      gene expression that characterizes neurons in limbic brain regions. Other studies
      in which the cellular environment is altered by prenatal cocaine exposure result
      in modified fetal neurotransmitter function and specific pharmacological and
      structural alterations in the cerebral cortex that lead to abnormal behavior. The
      cellular milieu of the developing central nervous system prenatally thus serves
      functions as critical as environmental stimuli postnatally that promote synaptic
      development and refinement.

PMID- 9578992
TI  - A critical period of brain development: studies of cerebral glucose utilization
      with PET.
AB  - Studies with positron emission tomography indicate that the human brain undergoes
      a period of postnatal maturation that is much more protracted than previously
      suspected. In the newborn, the highest degree of glucose metabolism
      (representative of functional activity) is in primary sensory and motor cortex,
      cingulate cortex, thalamus, brain stem, cerebellar vermis, and hippocampal
      region. At 2 to 3 months of age, glucose utilization increases in the parietal,
      temporal, and primary visual cortex; basal ganglia; and cerebellar hemispheres.
      Between 6 and 12 months, glucose utilization increases in frontal cortex. These
      metabolic changes correspond to the emergence of various behaviors during the
      first year of life. The measurement of absolute rates of glucose utilization
      during development indicates that the cerebral cortex undergoes a dynamic course
      of metabolic maturation that persists until ages 16-18 years. Initially, there is
      a rise in the rates of glucose utilization from birth until about age 4 years, at
      which time the child's cerebral cortex uses over twice as much glucose as that of
      adults. From age 4 to 10 years, these very high rates of glucose consumption are
      maintained, and only after then is there a gradual decline of glucose metabolic
      rates to reach adult values by age 16-18 years. Correlations between glucose
      utilization rates and synaptogenesis are discussed, and the argument is made that
      these findings have important implications with respect to human brain plasticity
      following injury as well as to "critical periods" of maximal learning capacity.

PMID- 9578993
TI  - The role of nutrition in brain development.
AB  - Common sense always links good nutrition with optimal development of infants and,
      particularly, of brain development. Fortunately, brain development is rather
      resistant to nutritional deficiencies, provided that the psychomotor stimulation
      of the baby is adequate, as shown by many authors in the case of global protein
      energy malnutrition. For two types of micronutrient deficiency, those of iron and
      long-chain polyunsaturated fatty acids, it is easier to isolate the role of
      micronutrient deficiency from the role of psychosocial deprivation, although not
      entirely. Term babies seem to be perfectly able to synthesize both
      docosahexaenoic acid (DHA) of the n-3 series and arachidonic acid (AA) of the n-6
      series in sufficient quantities for their normal brain development, provided that
      their diet contains the precursors of the two series in adequate proportions. For
      low-birth-weight infants, AA does not seems to be necessary, and the discussion
      is still open regarding the essentiality of DHA. For iron, it seems that the
      level of education of the mother affects both the iron status of the child and
      its psychomotor development. The additional role of iron deficiency on infection
      sensitivity and muscular strength could also have an effect on the overall
      nutritional status and on the ability to communicate with the environment and
      learn.

PMID- 9578994
TI  - Language input and language growth.
AB  - This report is concerned with the sources of language development in the child.
      We have found a substantial relation between naturally occurring variations in
      children's language environments and their language skills, both at the earliest
      stages of language development and later, at 5 and 6 years of age. Our studies
      show that children's language development is related to the speech they hear at
      home and the speech they hear at school. Although much more work remains to be
      done, it is clear that differences in language input within the normal range are
      causally related to the growth of children's vocabularies and their syntactic
      skills.

PMID- 9578995
TI  - Maternal depression effects on infants and early interventions.
AB  - Our recent research suggests that: (1) maternal depression negatively affects
      infants as early as the neonatal period, implicating prenatal effects of maternal
      depression; (2) as early as birth the infants show a profile of "dysregulation"
      in their behavior, physiology, and biochemistry which probably derives from
      prenatal exposure to a biochemical imbalance in their mothers; (3) these effects
      are compounded by the disorganizing influence of the mother's interaction
      behavior; (4) depressed mothers have two predominant interaction styles,
      withdrawn or intrusive, which seem to have differential, negative effects on
      their infants related to inadequate stimulation and arousal modulation; (5)
      nondepressed caregivers such as fathers may buffer these effects because they
      provide more optimal stimulation and arousal modulation; and (6) interventions
      that are mood altering for the mothers (e.g., music and massage therapy) and
      arousal reducing for the infants (e.g., the same therapies) make the mothers and
      infants more responsive to interaction coaching and improve their interactions.

PMID- 9578996
TI  - Long-term cognitive and academic effects of early childhood education on children
      in poverty.
AB  - It is generally accepted that early childhood education improves the cognitive
      performance of children in poverty in the short-term, but whether cognitive
      effects persist in the long-term is hotly debated. This paper presents the
      results of a critical review of 38 studies of the long-term effects of early
      childhood programs on children in poverty. Outcomes examined include IQ,
      achievement, and academic success as measured by grade repetition, special
      education placement, and high school graduation. Early childhood education is
      found to produce persistent effects on achievement and academic success, but not
      on IQ (with some exceptions). Head Start and public school programs produce the
      same types of effects as better funded model programs, but at least some of the
      effects are smaller. Cost-benefit analysis based on one randomized trial finds
      that the economic return from providing early education to children in poverty
      far exceeds the costs. Head Start, public school preschool education, and
      education in high-quality child care programs all offer avenues for government
      investment to improve the long-term cognitive development and academic success of
      children in poverty.

PMID- 9578997
TI  - Quality of early care and buffering of neuroendocrine stress reactions: potential
      effects on the developing human brain.
AB  - Brain development is affected by stress early in development. Activity of the
      hypothalamic-pituitary-adrenocortical (HPA) axis plays a role in mediating the
      effects of adversity on the developing brain. The impact of glucocorticoids on
      brain development has been studied in animal models. The literature linking
      activity of the HPA axis to memory, attention, and emotion in human children is
      briefly reviewed. Evidence for decreased reactivity of the HPA system developing
      over the first year of life is presented. Finally, the role of sensitive and
      responsive caregiving in buffering reactivity of the HPA system to potentially
      stressful events is described. It is argued that these data provide yet more
      support for the importance of fostering safe, secure care for children early in
      their development.

PMID- 9578998
TI  - A framework for: what can and should society do?
AB  - Researchers strive to better understand the critical periods of brain
      development. Findings generate clearer descriptions of what the critical periods
      are and suggest that stress, aggression, and violent behavior affect the
      development process. But the question remains as to what can and should society
      do to nurture children through these periods and to support their continued
      growth and development. Operation Peace in Philadelphia, an urban community
      based, violence prevention/reduction initiative using the principals of public
      health, represents a framework for generating fresh attitudes and innovative
      support systems that will nurture children through the critical periods of brain
      development and beyond. This framework enhances understanding of the complexities
      of societal issues such as violent behavior and uncovers and offers communal
      solutions. It is a link between research and its practical application--what
      society can do. Society's challenge echoes Operation Peace's challenge to use the
      combined strengths of scientific knowledge, multidisciplinary skills, sustained
      commitment, cultural vitality, community support, and political will to enable
      youth to achieve their potential, via full and active lives.

PMID- 9578999
TI  - Healthy Start: a comprehensive health education program for preschool children.
AB  - BACKGROUND: Healthy Start is a 3-year demonstration and education research
      project designed to evaluate the effectiveness of a multidimensional
      cardiovascular (CV) risk reduction intervention in preschool centers over a 3
      year period of time. METHODS: Two primary interventions are employed. The first
      is the preschool food service intervention program designed to reduce the total
      fat in preschool meals and snacks to less than 30% of calories and reduce the
      saturated fat to less than 10% of calories. The second major intervention is a
      comprehensive preschool health education curriculum, focused heavily on
      nutrition. RESULTS: Effectiveness of the intervention will be determined through
      evaluation of changes in dietary intake of preschool children at school meals and
      snacks, especially with respect to intake of total and saturated fat. Evaluation
      of the education component will include assessment of program implementation by
      teachers, assessment of changes in nutrition knowledge by preschool children, and
      assessment of changes in home meals that children consume (total and saturated
      fat content). Blood cholesterol will be evaluated semiannually to evaluate
      changes that may be due to modification of dietary intake. Growth and body
      fatness will also be assessed. CONCLUSIONS: While substantial efforts have
      targeted CV risk reduction and health education for elementary school children,
      similar efforts aimed at preschool children have been lacking. The rationale for
      beginning CV risk reduction programs for preschool children is based upon the
      premise that risk factors for heart disease are prevalent by 3 years of age and
      tend to track over time, most commonly hypercholesterolemia and obesity, both
      related to nutrition. Since the behavioral antecedents for nutritional risk
      factors begin to be established very early in life, it is important to develop
      and evaluate new educational initiatives such as Healthy Start, aimed at the
      primary prevention of cardiovascular risk factors in preschool children. The
      purpose of this publication is to describe the rationale and methods for the
      Healthy Start project.

PMID- 9579000
TI  - Prevention of intellectual disabilities: early interventions to improve cognitive
      development.
AB  - This paper presents a conceptual framework that has guided three randomized,
      controlled early intervention trials designed to improve cognitive development
      and social competence in high-risk young children from birth to 3 years of age.
      Two of the projects (Abecedarian and CARE) enrolled infants from economically and
      socially low-resource families and the other project (IHDP) was an eight-site
      randomized controlled trial with 985 low birth-weight and premature infants and
      their families. IHDP families varied widely in their economic and social
      resources. Results consistently indicated positive effects of the intervention on
      child IQ during the first 3 years of life. Children from the lowest resource
      families consistently benefited the most from the early intervention.

PMID- 9579001
TI  - Changing early childhood development through educational intervention.
AB  - A major issue in child development is the extent to which educational
      intervention can impact the pattern of growth. The High/Scope Perry Preschool
      study, which began in 1962, has now reported results through age 27. These
      findings indicate significantly improved social responsibility and educational
      performance in adult life by children who participated when compared with the
      randomly assigned nonparticipating group of children. A benefit-cost study found
      a return of $7.16 for each dollar invested. However, such outcomes are found only
      from specific, high-quality operations. The longitudinal High/Scope Curriculum
      Comparison study found that children who had experienced a highly intensive
      academic program were significantly less socially responsible at age 23 than were
      children from programs that encouraged individual choice and initiative. These
      studies indicate that children at ages 3 and 4 are at a sensitive period in their
      development toward stable adult-behavior patterns. High-quality early education
      programs can significantly improve adult adjustment and performance. However,
      such programs need to involve the child in active experiences and independent
      decision-making to be effective.

PMID- 9579002
TI  - The effectiveness of early intervention: examining risk factors and pathways to
      enhanced development.
AB  - In this paper we examine the effectiveness of early intervention, especially vis
      a-vis (a) child and family risk factors and (b) the pathways to enhanced child
      and family development. To address these issues we draw on findings from the
      Infant Health and Development Program (IHDP) for low-birth-weight premature
      infants. The data we present reveal the considerable effectiveness of the IHDP
      intervention in enhancing several aspects of early and later child and family
      development. The findings also illustrate the importance of looking beyond
      intervention group differences to examine the extent to which early intervention
      effects are more pronounced for some children and families than others and to
      examine the processes underlying intervention effects (e.g., exactly how do early
      interventions change children and families?). For example, both initial and
      longer-term IHDP intervention effects varied by both characteristics of the
      children and characteristics of their families. Our data also provide some
      insight into the processes by which intervention effects may have occurred. We
      conclude our consideration of these many complexities with suggestions for
      practice, social policy, and future research.

PMID- 9579003
TI  - Inside the brain: revolutionary discoveries of how the mind works.

PMID- 9579004
TI  - A feasibility test of a brief educational intervention to increase fruit and
      vegetable consumption among callers to the Cancer Information Service.
AB  - BACKGROUND: In this paper, results are reported from a pilot study designed to
      test the feasibility of a proactive educational intervention delivered to callers
      of the Cancer Information Service (CIS). METHODS: The study used a randomized two
      group design (intervention vs control). Callers assigned to the intervention
      condition received a brief educational intervention at the end of usual service
      to increase fruit and vegetable consumption. As part of the intervention, key
      education messages and materials drawn from the 5 A Day for Better Health program
      of the National Cancer Institute were provided to CIS callers over the telephone
      and then reinforced with two follow-up mailings. RESULTS: Results from this pilot
      study indicated high levels of adherence to protocol by CIS Information
      Specialists who delivered the intervention to eligible CIS callers. Results
      obtained from the 4-week telephone follow-up interviews indicated that
      intervention subjects (n = 142) reported higher consumption of fruits and
      vegetables, averaging approximately 0.75 servings more per day (P < 0.01) than
      control subjects (n = 134). CONCLUSION: Nearly 80% of CIS callers endorsed the
      strategy of providing 5 A Day information at the end of usual service, even if
      such information was not specifically requested by the caller (i.e., the
      information was provided to CIS callers proactively.

PMID- 9579005
TI  - Effectiveness of nicotine-containing gum in the Physician-Delivered Smoking
      Intervention Study.
AB  - BACKGROUND: We tested the role of nicotine-containing gum (NCG) in conjunction
      with brief physician counseling in smoking cessation in the Physician-Delivered
      Smoking Intervention Project (PDSIP). METHOD: Subjects were smokers randomized to
      the Counseling + NCG arm of the PDSIP. However, receipt and use of NCG were not
      randomized. Data from base-line, were not randomized. Data from baseline,
      pharmacy records, and 6-month monitoring calls were used in these post hoc
      analyses. RESULTS: Of the 299 study subjects, 57% accepted NCG and 36% of
      acceptors used it for more than 7 days. Predictors of NCG acceptance included
      high desire to quit (OR = 1.21; 95% CI 1.10, 1.35), social support to quit (OR =
      1.62; 95% CI 1.01, 2.59), being a general medicine patient compared with a family
      practice patient (OR = 3.22; 95% CI 2.01, 5.21), and receiving the intervention
      from a female physician (female physician-male patient OR = 2.27; 95% CI 0.95,
      5.46; female physician-female patient OR = 1.94; 95% CI 1.06, 3.57) relative to
      the male physician comparisons. Subjects who refilled the NCG prescription had
      higher cessation rates than those who did not refill or did not accept the
      prescription (37% vs 19% and 20%, respectively; P = 0.04). Predictors of 6-month
      cessation among NCG users included a previous period(s) of abstinence > 3 months
      (OR = 1.23; 95% CI 1.04, 1.47), abstinence during illness (OR = 0.39; 95% CI
      0.17, 0.86), and absence of smoking-related physical complaints the month prior
      to the physician-delivered intervention (OR = 0.40; 95% CI 0.17, 0.94).
      CONCLUSION: Amount of NCG use in conjunction with physician-delivered smoking
      cessation counseling might have contributed in helping unselected smokers quit.

PMID- 9579006
TI  - Mother's knowledge of, attitudes toward, and management of fever in preschool
      children in Italy.
AB  - BACKGROUND: We examined mothers' knowledge of, attitudes toward, and management
      of fever in their children. METHODS: Interviews of mothers of preschool children
      were performed using a structured questionnaire administered by interviewers with
      no specific medical competence. RESULTS: Of a total of 1,237 mothers who were
      interviewed, data were analyzed for the 707 mothers who had coped with a febrile
      episode in their children during the previous month. Of these, 59% were concerned
      about fever in their children and 17% were very worried. At the onset of fever,
      48% of the mothers gave their child an antipyretic and 18% called the physician
      immediately. In logistic regression analysis, five variables were significantly
      associated with mothers' concern: the absence of previous information on the
      management of fever, temperature > 39 degrees C, an only child, mother's low
      educational level, and mother's residency in the south of Italy. For the request
      for a physician's visit, of the variables entered, the only explanatory ones were
      the mother's concern and the absence of previous information on the management of
      fever. CONCLUSIONS: These findings suggest that informing mothers on the
      definition, consequences, and treatment of fever can significantly improve their
      confidence in managing fever, as reflected by fewer requests for physicians'
      visits.

PMID- 9579007
TI  - Reproducibility and accuracy among primary care providers of a screening
      examination for foot ulcer risk among diabetic patients.
AB  - BACKGROUND: A clinical examination has been shown to stratify patients by risk
      for diabetic foot ulcer; it is unknown whether primary care providers can
      reproducibly perform this examination. METHODS: One hundred forty-seven
      consecutive diabetic patients at six Veterans Affairs Medical Centers received a
      structured history and physical examination of the feet from each of two primary
      care providers; 88 of these patients were also examined by a foot care
      specialist. The examination consisted of a previously validated four-component
      diabetic foot ulcer risk stratification examination and a vascular disease
      history and physical examination. RESULTS: Seventy-nine percent of patients were
      assessed as having elevated risk for development of foot ulcer. Interobserver
      agreement for risk stratification was moderate (kappa = 0.51; 95% CI 0.40, 0.62).
      The agreement for individual components of the stratification examination was
      variable, with kappa statistics ranging from 0.36 to 0.91. Primary care providers
      had good sensitivity and specificity for most components of the examination
      (compared with foot care specialist's examination as the criterion standard), but
      frequently were unable to identify pedal pulses [sensitivity 0.52 (95% CI 0.41,
      0.61)] or foot deformity [sensitivity 0.51 (95% CI 0.46, 0.56)]. CONCLUSIONS: A
      validated risk stratification foot examination for diabetic patients is
      reproducible and largely accurate when performed by primary care providers.

PMID- 9579008
TI  - Intention to screen for colorectal cancer among white male employees.
AB  - BACKGROUND: This study identifies factors associated with employee intention to
      participate in a company-sponsored program of continuous screening for colorectal
      cancer. Automobile industry pattern and model makers who had been offered
      screening for over a decade were included in the study. METHODS: Data were
      collected at the outset of a randomized trial of screening and nutrition
      interventions. A baseline survey was mailed to 4,490 white men without a history
      of colorectal cancer. This mailing generated complete responses from 2,693 (60%)
      individuals. Survey data obtained for these men, including measures of cognitive
      and psychological representations related to colorectal screening, social
      influence, and intention to screen, were supplemented by background information
      gathered from employment records of these men. Workplace screening services were
      documented via a survey of plant health care professionals. RESULTS: Fifty-eight
      percent of respondents reported a high level of intention to screen. Multivariate
      analyses showed that intention to screen was positively associated with employee
      past participation in screening, belief in the salience and coherence of
      screening, belief in screening efficacy, perceived self-efficacy, belief that
      polyp removal prevents colorectal cancer, perceived personal susceptibility to
      colorectal cancer or polyps, receptivity to family member support for screening,
      and workplace scheduling of screening examinations. CONCLUSIONS: Factors
      associated with intention to screen may contribute to participation in continuous
      screening programs. Research is needed to assess the impact of interventions that
      facilitate appointment scheduling, provide tailored education about screening,
      and encourage lay support.

PMID- 9579009
TI  - Evaluation of an 8-week mailed healthy-weight intervention.
AB  - BACKGROUND: This study investigated the impact of a low-intensity, healthy-weight
      intervention among adult volunteers in a low-income, inner-city neighborhood. The
      intervention, which comprised 18 pamphlets mailed to participants' homes over 8
      weeks, focused on increasing awareness of healthy weight ranges, increasing self
      acceptance and satisfaction with weight, and improving eating habits, while
      downplaying dieting and weight loss. METHODS: Subjects were recruited from
      households randomly selected from residential telephone subscriber lists. The 188
      volunteers (23.0% of 816 persons contacted) were randomly assigned to
      intervention or control status. Psychosocial and behavioral measures were
      administered by telephone 1 week before and 2 weeks after the intervention.
      RESULTS: After exposure to the pamphlets, intervention subjects were more likely
      than controls to know how to control their weight. They were more satisfied with
      their weight and less likely to report they were too heavy. They reported less
      high-fat/junk food consumption, more improvements in their eating habits, and
      more frequent exercise. CONCLUSION: This inexpensive, low-intensity intervention
      was effective in supporting change processes among volunteers who wanted to learn
      about weight control, to improve eating habits, and to improve health.

PMID- 9579010
TI  - Transdermal nicotine replacement for hospitalized patients: a randomized clinical
      trial.
AB  - BACKGROUND: This study was undertaken to assess the safety and efficacy of a
      treatment involving brief counseling and the nicotine patch among hospital
      inpatients and to identify variables associated with long-term smoking cessation
      following hospitalization. METHODS: One hundred eighty-five patients were
      randomly assigned to one of three smoking cessation interventions: (1) A Minimal
      Care (MC) condition, consisting of a brief physician-delivered motivational
      message to stop smoking, (2) a Counseling + Active Nicotine Patch (CAP) condition
      in which patients received the motivational message, a 6-week supply of nicotine
      patches, and extended bedside and telephone counseling, and (3) a Counseling +
      Placebo Patch (CPP) condition identical to the CAP condition except the supplied
      patches contained no nicotine. RESULTS: At 6-month follow-up, abstinence rates
      for the three treatments were 4.9, 6.5, and 9.7% for the MC, CPP, and CAP
      treatments, respectively. These differences were not statistically significant.
      Patients admitted for respiratory disease were more likely to quit than patients
      with any other diagnosis. The nicotine patch was well tolerated by hospital
      inpatients. CONCLUSIONS: The initiation of nicotine patch therapy during
      hospitalization appears to be safe when used among patients carrying a wide range
      of diagnoses. Our study provided no evidence of the superiority of nicotine
      patches versus placebo, but this does not preclude the possibility that future
      research using larger samples might detect differences between patch groups.
      Hospital interventions for smoking cessation may be most effective among patients
      hospitalized for a smoking-related illness such as respiratory disease.

PMID- 9579011
TI  - Re: Cost-effectiveness of the nicotine transdermal patch.

PMID- 9579012
TI  - Measurement of passive smoking.

PMID- 9579013
TI  - Streamlining outpatient geriatric assessment: essential social, environmental and
      economic variables.
AB  - There are no known standardized instruments that encompass all of the essential
      elements of a streamlined outpatient geriatric assessment. A process of arriving
      at a consensus on essential elements of streamlined geriatric assessment in 3
      domains was initiated and described. Two rounds of the Delphi technique were
      conducted to identify social, environmental and economic variables essential for
      such an assessment. Consensus among an expert panel was achieved and a list of 27
      variables was reduced to 16. This result is discussed in terms of assessment
      context and standardizing assessment, using case examples.

PMID- 9579014
TI  - Triage services: a profile of high utilization.
AB  - With challenges continuing to be presented to health care delivery, inappropriate
      out-patient service utilization is of utmost concern to all health care service
      providers. This study is an examination of the utilization patterns of 189
      veterans in an urban Veterans Administration Medical Center (VAMC). Factors found
      to be related to high utilization of ambulatory care triage clinic services for
      veterans who had presented for at least two unscheduled visits in the past six
      months include: patient perception of health status; number of prescription
      medications; and social needs. Implications for social work practice, program
      development and research are discussed.

PMID- 9579015
TI  - Debriefing of American Red Cross personnel: pilot study on participants'
      evaluations and case examples from the 1994 Los Angeles earthquake relief
      operation.
AB  - The Multiple Stressor Debriefing (MSD) model was used to debrief 112 American Red
      Cross workers individually or in groups after their participation in the 1994 Los
      Angeles earthquake relief effort. Two composite case examples are presented that
      illustrate individual and group debriefings using the MSD model. A questionnaire
      which evaluated workers' experience of debriefing, was completed by 95 workers.
      Results indicated that workers evaluated the debriefings in which they
      participated positively. In addition, as participant to facilitator ratio
      increased, workers shared less of their feelings and reactions about the disaster
      relief operation. These findings, as well as more specific issues about
      debriefing, are discussed.

PMID- 9579016
TI  - Perceptions of social work intervention with bereaved clients: some implications
      for hospital social work practice.
AB  - The study focussed on social work bereavement intervention in a large Australian
      teaching hospital comparing client and social work perceptions of the service
      provided. The study involved the completion of a series of questionnaires and
      client interviews over a three month period. A combination of content and
      statistical analysis was used to interpret the findings. Eighty-eight percent of
      clients contacted indicated satisfaction with the social work service received.
      The results indicated a positive match between clients' and social workers'
      perceptions of the intervention, and affirmed the role of social work in
      bereavement care. Seventy percent of clients made recommendations regarding
      potential improvements to social work services. These recommendations contained
      four specific suggestions: that social workers be present when the doctor breaks
      bad news; that additional support be provided in how to talk to doctors; that
      social workers be involved from the point of admission of the patient; and that a
      primary social worker remain with the family throughout the hospital stay.

PMID- 9579017
TI  - Planning psychosocial care for cancer patients: if at first you don't succeed,
      shift your paradigm.
AB  - Concerned with our capacity to bridge the gap between patients' and families'
      psychosocial needs and the services provided, we developed a psychosocial intake
      and referral service. This paper will describe the lessons learned in trying to
      introduce an innovation whose time had not yet come and, after analyzing the
      outcome, to present a new approach to planning. The service was not approved and,
      on reflection, eight factors were identified as contributing to the failure of
      the service to reach fruition. In light of what we learned, we developed a new
      planning model that reflects planning as a circular, iterative process rather
      than as a linear process.

PMID- 9579018
TI  - The experience and preparation of pediatric sibling bone marrow donors.
AB  - To assist sibling bone marrow donors with the psychological and emotional
      distress that they may experience as donors, a sibling bone marrow donor program
      was developed at The Hospital for Sick Children. These donors feel overwhelming
      responsibility for their siblings' survival, which can lead to psychological
      distress. The donors are engaged in age-appropriate medical play and are
      encouraged to discuss their feelings and concerns about their role. After the
      marrow harvest, donors receive a certificate, and either they or their parents
      evaluate the program. Thus far, 97.5% have rated the program very helpful. These
      evaluations suggest that the program has a very positive effect on the sibling
      donor's psychosocial health. Further studies of the program's long-term success
      are warranted.

PMID- 9579019
TI  - Metabolism and disposition of phenolphthalein in male and female F344 rats and
      B6C3F1 mice.
AB  - A recent 2-year carcinogenicity/toxicology study determined that phenolphthalein
      (PHTH) is a multisite carcinogen in both mice and rats at all doses evaluated. In
      response to this finding the metabolism and disposition of PHTH has been
      evaluated in both F344 rats and B6C3F1 mice at a single oral dose of 800 mg/kg.
      This dose fell within the range previously found to be carcinogenic in rats and
      mice. Studies were also performed using 1 and 50 mg/kg doses. At 800 mg/kg
      recovery of [14C]PHTH after 72 h was near 100% in females but closer to 75% in
      males. Radioactivity was primarily recovered in the feces in rats (> 90%), while
      mice excreted 30-40% of administered activity in the urine. There was no
      significant retention of radioactivity in tissues by 72 h and no significant
      accumulation of radioactivity in any tissue at any time point. Covalent binding
      to protein in target tissues, bone marrow and ovary, was at or less than the
      pmol/mg protein range. The major metabolite was PHTH glucuronide. Three minor
      metabolites were detected. A sulfate conjugate and and a hydroxylated metabolite
      were identified by comparison of retention times and 1H NMR and/or mass spectra
      with synthetic standards. A diglucuronide conjugate was tentatively identified.
      Biliary elimination was extensive in rats (35% of dose within 6 h); the only
      product detected in bile was phenolphthalein glucuronide.

PMID- 9579020
TI  - The cruciferous nitrile, crambene, induces rat hepatic and pancreatic glutathione
      S-transferases.
AB  - Indoles and isothiocyanates found in cruciferous vegetables have been implicated
      as chemopreventive agents against carcinogenesis. The bioactivities of chemically
      related cruciferous nitriles, including 1-cyano-2-hydroxy-3-butene (crambene),
      however, have not been thoroughly evaluated. Crambene causes a prolonged
      elevation of rat hepatic and pancreatic glutathione and induces the GSH S
      transferases (GSTs). Because elevated GST activity against the model substrate
      chlorodinitrobenzene does not reflect individual isoenzyme induction,
      quantitative HPLC evaluation of specific GST subunits is necessary to fully
      assess the range of GST isoenzymes induced by crambene. Accordingly, male Fischer
      344 rats were given, via esophageal intubation, either 100 (Experiment 1) or 50
      mg crambene/kg body wt (Experiment 2) once daily for 7 days. GSTs were extracted
      from hepatic cytosol by affinity chromatography, and the individual subunits that
      comprise the various isoenzymes were quantified by reverse-phase HPLC to gain an
      estimate of induction. In addition, pancreatic GST subunits were assessed in the
      low-dose experiment. In parallel with increased GST activity, crambene caused a
      generalized induction of GST subunits in both liver and pancreas, but the pattern
      of subunit induction was tissue dependent. In the liver, alpha subunits 1 and 2
      and the mu subunit 3 were induced approximately 2-fold, while the mu subunit 4
      was induced only 1.5-fold. In the pancreas, the alpha subunit 2 was induced to a
      much larger extent (2.6-fold) than the other subunits (from no induction to 1.6
      fold). These results suggests that crambene-mediated GST induction mechanisms
      vary from tissue to tissue. Potential chemoprevention provided by crambene
      against GST-metabolized carcinogens or toxins may differ between liver and
      pancreas because of differences in the degree and pattern of induction.

PMID- 9579021
TI  - Pyrimethamine impairs host resistance to infection with Listeria monocytogenes in
      BALB/c mice.
AB  - Increased mortality has been observed when HIV-infected patients were treated
      with pyrimethamine (Pyr) as prophylaxis for toxoplasmic encephalitis, suggesting
      that Pyr might possess immunosuppressive activity. To analyze this in an animal
      model, immune function was assessed in BALB/c mice using a battery of in vivo and
      ex vivo assays and an in vivo model of host resistance to Listeria monocytogenes
      infection. Treatment for 30 days with 60 mg/kg Pyr decreased circulating white
      blood cell and lymphocyte counts but not neutrophil, red blood cell, or platelet
      counts or hemoglobin levels. Splenic B cell percentages and lipopolysaccharide
      induced B cell proliferation decreased significantly after treatment with 60
      mg/kg Pyr, as did levels of anti-keyhole limpet hemocyanin (KLH) IgM in serum 7
      days after immunization with KLH. Anti-KLH IgG levels 14 days after immunization
      were not affected. Percentages of splenic T cells and macrophages and T cell
      proliferation in the presence of concanavalin A or allogeneic cells were not
      decreased by Pyr treatment. An ex vivo assay of T-cell-mediated cytotoxicity was
      also unaffected. When host resistance to L. monocytogenes infection was assessed,
      dramatic increases in mortality were observed in Pyr-treated compared to control
      mice. Increased numbers of L. monocytogenes organisms were observed in liver and
      spleen of Pyr-treated mice, compared to controls. The reduction in Listeria
      resistance, which is T cell mediated, contrasts with the fact that no significant
      changes in T-cell-mediated immunity were observed. It is possible that Pyr
      affects parameters of innate immunity, which were not monitored in this study.

PMID- 9579022
TI  - Enteric reovirus infection as a probe to study immunotoxicity of the
      gastrointestinal tract.
AB  - The gastrointestinal (GI) tract contains a complex immune system that defends the
      host against a wide range of pathogens and toxins. The GI tract is also exposed
      to many environmental toxins that could adversely affect intestinal immunity, and
      few systems to study immunotoxicity of the GI tract have been described. We
      demonstrate that intestinal reovirus infection can be used as a system to assess
      the effects of toxins on intestinal and systemic immunity. Mice were given
      various doses of cyclophosphamide (CY) for 5 days at doses ranging from 100 to
      500 mg/kg by the oral route or 200 mg/kg by the intraperitoneal route. On day 3
      of dosing, mice were orally infected with reovirus serotype 1, strain Lang. The
      effects of CY on viral clearance, intestinal and systemic immune responses, and
      distribution of intestinal lymphocytes were assessed. Mice treated with CY failed
      to clear the virus in a dose-dependent manner, and serum anti-reovirus antibody
      titers were suppressed. Virus-specific IgA in cultures of intestinal tissue from
      CY-treated mice was significantly reduced compared to controls, although total
      IgA production was not affected. The virus-specific cytotoxic T-cell response in
      spleen was also suppressed in CY-treated animals. Cyclophosphamide treatment
      reduced the number and percentage of B-cells in Peyer's patches. Reovirus
      infection did not increase cellularity of Peyer's patches in CY-treated mice.
      Cyclophosphamide treatment also had little effect on the phenotype of intestinal
      intraepithelial lymphocytes. These data demonstrate that intestinal reovirus
      infection is useful in studying exposure of the GI tract to immunotoxic agents.

PMID- 9579023
TI  - Bcl-2 and Bcl-xL in peroxide-resistant A549 and U87MG cells.
AB  - Overexpression of the bcl-2 and the related bcl-xL protooncogene proteins enhance
      cell survival by inhibiting apoptosis induced by many agents including oxidants.
      Whether these proteins contribute to survival in oxidant-resistant cells is not
      known. The current study assessed the expression of bcl-2 and bcl-xL proteins in
      human glioblastoma U87MG cells and human lung adenocarcinoma A549 cells selected
      for resistance to 0, 50, 100, 200, and 400 microM H2O2 by exposure to this
      oxidant one time each passage for 9 months. When examined 7 to 32 days after
      cessation of peroxide exposure (times when peroxide resistance was maintained),
      bcl-2 protein levels were significantly increased in most peroxide-resistant
      U87MG cells. However, the increase was not dose dependent and was not accompanied
      by an increase in mRNA levels. A549 cells did not express significant levels of
      bcl-2 protein, although bcl-2 mRNA was detectable. A549 cells expressed large
      amounts of bcl-xL and immunohistochemistry demonstrated extensive localization of
      this protein around the nucleus. However, expression of this protein was not
      altered in peroxide-resistant lines nor was bcl-2 protein increased to a
      measurable level. U87MG cells also expressed bcl-xL but it was not altered in
      peroxide-resistant cells. Although the increased bcl-2 protein in peroxide
      resistant U87MG cells may contribute to their oxidant tolerance, the lack of a
      dose-response relationship, the failure to induce bcl-xL protein, and the absence
      of any bcl-2 or bcl-xL protein induction in peroxide-resistant A549 cells suggest
      these genes are not primary factors in oxidant resistance.

PMID- 9579024
TI  - Female Sprague-Dawley rats exposed to a single oral dose of 2,3,7,8
      tetrachlorodibenzo-p-dioxin exhibit sustained depletion of aryl hydrocarbon
      receptor protein in liver, spleen, thymus, and lung.
AB  - There is currently little information concerning the time-dependent relationship
      between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and aryl hydrocarbon
      receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) protein
      concentration in vivo. Therefore, female Sprague-Dawley rats were given a single
      oral dose of TCDD (10 micrograms/kg), and the AHR and ARNT protein concentrations
      in liver, spleen, thymus, and lung determined by Western blotting. In liver, the
      concentration of AHR protein was significantly reduced 8 and 24 h postdosing as
      compared to time-matched controls. In spleen and lung, the concentration of AHR
      protein was reduced 3, 8, 24, and 168 h posttreatment compared to time-matched
      controls but returned to control levels by 336 h. In thymus, reductions in AHR
      protein concentration were observed 8, 24, 168, and 336 h postdosing as compared
      to time-matched controls. Significant reductions in the concentration of ARNT
      protein were not observed in any of the TCDD-exposed tissues. Functional studies
      in cell culture showed that exposure of a mouse hepatoma cell line (Hepa-1c1c7)
      and a rat smooth muscle cell line (A-7) to TCDD (1 nM) for 12 days resulted in a
      50% reduction in TCDD-inducible reporter gene expression following subsequent
      challenge by an additional dose of TCDD (1 nM). Collectively, these results show
      that (i) TCDD-mediated depletion of AHR occurs in vivo, (ii) AHR protein does not
      rapidly recover to pretreatment levels even though the tissue concentration of
      TCDD has fallen, and (iii) reduction in AHR protein concentration correlates with
      reduction in TCDD-mediated reporter gene expression in mammalian culture cells.

PMID- 9579025
TI  - Developmental exposure to lead causes persistent immunotoxicity in Fischer 344
      rats.
AB  - Lead has been shown to exert toxic effects during early development. In these in
      vivo and ex vivo experiments, the effect of lead on the immune system of the
      developing embryo was assessed. Nine-week-old female Fischer 344 rats were
      exposed to lead acetate (0, 100, 250, and 500 ppm lead) in their drinking water
      during breeding and pregnancy (exposure was discontinued at parturition).
      Offspring received no additional lead treatment after birth. Immune function was
      assessed in female offspring at 13 weeks of age. Dams in lead-exposed groups were
      not different from controls with respect to the immune endpoints used in these
      experiments; however, in the offspring, lead modulated important immune
      parameters at modest exposure levels. Macrophage cytokine and effector function
      properties (tumor necrosis factor-alpha and nitric oxide production) were
      elevated in the 250 ppm group, while cell-mediated immune function was depressed,
      as shown by a decrease in delayed-type hypersensitivity reactions in the 250 ppm
      group. Interferon-gamma levels were decreased in the 500 ppm treatment group.
      Serum levels of IgE were increased in rats exposed to 100 ppm lead. These results
      indicate that exposure of mothers to moderate levels of lead produces chronic
      immune modulation in their F344 rat offspring exposed in utero. Since the mothers
      were not susceptible to chronic immune alterations, a developmental bias to the
      immunotoxic effects of lead is indicated. The differences observed are consistent
      with the possibility that lead may bias T helper subset development and/or
      function, resulting in alterations in the balance among type 1 and type 2 immune
      responses.

PMID- 9579026
TI  - Isobutyraldehyde administered by inhalation (whole body exposure) for up to
      thirteen weeks or two years was a respiratory tract toxicant but was not
      carcinogenic in F344/N rats and B6C3F1 mice.
AB  - Isobutyraldehyde (a chemical structurally related to formaldehyde and used as a
      flavoring agent) was studied for toxicity and carcinogenicity by exposing male
      and female F344/N rats and B6C3F1 mice. Animals were exposed to isobutyraldehyde
      vapors 6 h per day, 5 days per week for up to 13 weeks or 2 years. In the 13-week
      studies, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were exposed
      to concentrations of 0, 500, 1000, 2000, 4000, or 8000 ppm. Chemical-related body
      weight depression and deaths occurred in rats and mice exposed to 4000 and 8000
      ppm. Necrosis of the epithelium accompanied with acute inflammatory reaction was
      observed in the nasal turbinate, larynx, and trachea of rats exposed to 8000 ppm.
      Exposure of rats to 4000 ppm resulted in metaplasia of the nasal respiratory
      epithelium, inflammation, degeneration of the olfactory epithelium, and
      osteodystrophy of the nasal turbinate bone. In the 13-week mouse study, exposure
      to 8000 ppm or 4000 ppm resulted in necrosis of the epithelium lining of the
      nasal turbinates. Osteodystrophy of the nasal turbinate bone and squamous
      metaplasia of the nasal respiratory epithelium were noted in mice exposed 4000
      ppm. Degeneration of the olfactory epithelium was noted in males exposed 2000 ppm
      and in females exposed to 4000 ppm. In the 2-year studies, groups of 50 male and
      50 male F344/N rats and B6C3F1 were exposed to concentrations isobutyraldehyde
      vapors of 0, 500, 1000, or 2000 ppm 6 h per day, 5 days per week. There were no
      differences in survival rates or mean body weights between exposed groups and
      control rats. Survival of male mice exposed to 2000 ppm and mean body weights of
      female mice exposed to 1000 or 2000 ppm were lower than those of the of the
      controls. No increase in neoplasm incidence was observed in rats and mice in the
      2-year studies that could be attributed to isobutyraldehyde exposure. Chemical
      related nonneoplastic lesions were limited to the nose of rats and mice. They
      included squamous metaplasia of the respiratory epithelium (rats), suppurative
      inflammation (rats), and olfactory epithelial degeneration (rats and mice) at
      1000 and 2000 ppm.

PMID- 9579027
TI  - Short communication: renal tubular vacuolation in animals treated with
      polyethylene-glycol-conjugated proteins.
AB  - During toxicologic evaluation of a dimeric PEG-linked protein, tumor necrosis
      factor binding protein (TNF-bp), vacuolation of renal cortical tubular epithelium
      was seen in male and female Sprague-Dawley rats (200-300 g) given i.v. doses of
      40, 20, or 10 mg/kg every other day for 3 months. Tubular lesions in rats treated
      with 20 or 40 mg/kg for 3 months were only partially reversible after a 2-month
      recovery period. Despite the presence of marked vacuolation, there were no
      changes in BUN, creatinine, urinalysis parameters, urinary NAG, urinary B2
      microglobulin, or fractional sodium excretion. Single i.v. doses > or = 20 mg/kg
      TNF-bp caused similar but milder changes. However, equivalent doses of PEG alone
      or the non-PEG-linked TNF-bp did not cause light microscopic evidence of
      vacuolation. Treatment of rats with another PEG-linked protein of similar
      molecular weight resulted in similar changes. Immunostaining for TNF-bp revealed
      positivity in the apical cytoplasm of renal tubular epithelium within 1 h of i.v.
      dosing. Immunostaining of kidneys from chronically dosed rats indicated that
      protein was present in some vacuoles as long as dosing continued; however,
      kidneys from animals on a reversibility study had vacuoles but no immunostaining
      for TNF-bp. These results, along with a study that showed more severe lesions
      with PEG-linked proteins of lower molecular weight and minimal if any lesions
      with PEG-linked proteins > 70 kDa, suggest that TNF-bp is filtered through the
      glomerulus and that the protein with attached PEG is reabsorbed by the proximal
      tubules. Vacuolation may be a result of fluid distension of lysosomes due to the
      hygroscopic nature of PEG. These studies demonstrated that PEG-linked proteins
      have the capacity to induce renal tubular vacuolation at high doses. However, the
      change was not associated with alteration of clinical pathology or functional
      markers.

PMID- 9579028
TI  - Tissue repair response as a function of dose during trichloroethylene
      hepatotoxicity.
AB  - Trichloroethylene (TCE), a widely used organic solvent and degreasing agent, is
      regarded as a hepatotoxicant. The objective of the present studies was to
      investigate whether the extent and timeliness of tissue repair has a determining
      influence on the ultimate outcome of hepatotoxicity. Male Sprague-Dawley rats
      (200-250 g) were injected with a 10-fold dose range of TCE and hepatotoxicity and
      tissue repair were studied during a time course of 0 to 96 h. Light microscopic
      changes as evaluated by H&E-stained liver sections revealed a dose-dependent
      necrosis of hepatic cells. Maximum liver cell necrosis was observed at 48 h after
      the TCE administration. However, liver injury as assessed by plasma sorbitol
      dehydrogenase (SDH) showed a dose response over a 10-fold dose range only at 6 h,
      whereas alanine aminotransferase (ALT) did not show a dose response at any of the
      time points studied. A low dose of TCE (250 mg/kg) showed an increase in SDH at
      all time points up to 96 h without peak levels, whereas higher doses showed peak
      only at 6 h. At later time points SDH declined but remained above normal. In
      vitro addition of trichloroacetic acid, a metabolite of TCE to plasma, decreased
      the activities of SDH and ALT indicating that metabolites formed during TCE
      toxicity may interfere with plasma enzyme activities in vivo. This indicates that
      the lack of dose-related increase in SDH and ALT activities may be because of
      interference by the TCE metabolite. Tissue regeneration response as measured by
      [3H]thymidine incorporation into hepatocellular nuclear DNA was stimulated
      maximally at 24 h after 500 mg/kg TCE administration. A higher dose of TCE led to
      a delay and diminishment in [3H]thymidine incorporation. At a low dose of TCE
      (250 mg/kg) [3H]thymidine incorporation peaked at 48 h and this could be
      attributed to very low or minimal injury caused by this dose. With higher doses
      tissue repair was delayed and attenuated allowing for unrestrained progression of
      liver injury. These results support the concept that the toxicity and repair are
      opposing responses and that a dose-related increase in tissue repair represents a
      dynamic, quantifiable compensatory mechanism.

PMID- 9579029
TI  - A methodological basis for description and analysis of systems with complex
      switch-like interactions.
AB  - A wide range of complex systems appear to have switch-like interactions, i.e.
      below (or above) a certain threshold x has no or little influence on y, while
      above (or below) this threshold the effect of x on y saturates rapidly to a
      constant level. Switching functions are frequently described by sigmoid functions
      or combinations of these. Within the context of ordinary differential equations
      we present a very general methodological basis for designing and analysing models
      involving complicated switching functions together with any other non
      linearities. A procedure to determine position and stability properties of all
      stationary points lying close to a threshold for one or several variables, so
      called singular stationary points, is developed. Such points may represent
      homeostatic states in models, and are therefore of considerable interest. The
      analysis provides a profound insight into the generic effects of steep sigmoid
      interactions on the dynamics around homeostatic points. It leads to qualitative
      as well as quantitative predictions without using advanced mathematical methods.
      Thus, it may have an important heuristic function in connection with numerical
      simulations aimed at unfolding the predictive potential of realistic models.

PMID- 9579030
TI  - Uniqueness of limit cycles in models for microparasitic and macroparasitic
      diseases.
AB  - The aim of this paper is to prove the uniqueness of isolated periodic solutions
      (i.e. limit cycles) in two simple models for microparasitic and macroparasitic
      diseases. Both models are described by systems of planar autonomous ordinary
      differential equations. After transformation of these systems to generalized
      Lienard systems, we will apply a modified theorem of Zhang and Dulac's criterion
      to prove the uniqueness of limit cycles.

PMID- 9579031
TI  - Analysis of model for macroparasitic infection with variable aggregation and
      clumped infections.
AB  - A model for macroparasitic infection with variable aggregation i considered. The
      starting point is an immigration-and-death process for parasites within a host,
      as in [3]; it is assumed however that infections will normally occur with several
      larvae at the same time. Starting from here, a four-dimensional, where free
      living larvae are explicitly considered, and a three-dimensional model are
      obtained with same methods used in [26]. The equilibria of these models are
      found, their stability is discussed, as well as some qualitative features. It has
      been found that the assumption of "clumped" infections may have dramatic effects
      on the aggregation exhibited by these models. Infections with several larvae at
      the same time also increases the stability of the endemic equilibria of these
      models, and makes the occurrence of subcritical bifurcations (and consequently
      multiple equilibria) slightly more likely. The results of the low-dimensional
      model have also been compared to numerical simulations of the infinite system
      that describes the immigration-and-death process. It appears that the results of
      the systems are, by and large, in close correspondence, except for a parameter
      region where the four-dimensional model exhibits unusual properties, such as the
      occurrence of multiple disease-free equilibria, that do not appear to be shared
      by the infinite system.

PMID- 9579032
TI  - Discrete chiasma formation models and their associated high order interference.
AB  - We introduce some special chiasma formation processes. First a family of discrete
      chiasma formation processes is introduced and we determine the nature of higher
      order interference associated with those processes. Secondly we consider a two
      stage chiasma formation process, where the associated recombination frequency
      between two markers depends not only on their map distance but also on their
      location along the chromosomes. We characterise under this process, in some
      cases, the nature of interference between two segments.

PMID- 9579033
TI  - Preparation of alkyl-substituted indoles in the benzene portion. Part 15.
      Asymmetric synthesis of (+)-duocarmycin SA using novel procedure for preparation
      of hydroxyindoles.
AB  - An asymmetric total synthesis of natural (+)-duocarmycin SA (1) starting from L
      malic acid (7) was achieved as shown in Chart 5, establishing firmly the absolute
      configuration of 1. In order to find suitable reaction conditions for the key
      step, i.e., the formation of an alkoxyindole derivative, model compounds 9 and 40
      were synthesized and two acetalization conditions using i) 2-ethyl-2-methyl-1,3
      dioxane and boron trifluoride etherate, and ii) 1,3-bis(trimethylsilyloxy)propane
      and trimethylsilyl triflate were found to be effective. The former conditions
      were successfully applied to total synthesis and 49b was prepared from 48 in 54%
      yield. Further elaborations including i) Curtius rearrangement of 53b to 56, and
      ii) cleavage of the primary benzyloxy group in the presence of the secondary one
      in its close vicinity (56-->57) led to the relay compound 62, whose conversion to
      1 has already been accomplished.

PMID- 9579034
TI  - Synthesis and enzymatic hydrolysis of esters, constituting simple models of soft
      drugs.
AB  - One way to minimise systemic side effects of drugs is to design molecules, soft
      drugs, in such a way that they are metabolically inactivated rapidly after having
      acted on their pharmacological target. Hydrolases (esterases, peptidases,
      lipases, glycosidases, etc.) are enzymes well suited to use for drug inactivation
      since they are ubiquitously distributed. Insertion of ester bonds susceptible to
      enzymatic cleavage may represent one approach to make the action of a drug more
      restricted to the site of application. The present study describes the chemical
      synthesis of fourteen model compounds comprising a bicyclic aromatic unit
      connected by an ester-containing bridge to another aromatic ring. Initial
      attempts to define a) the tissue selectivity of the hydrolytic metabolism and b)
      the molecular structural factors affecting the rate of enzymatic ester cleavage
      are presented. The data show that human and rat liver fractions were more active
      than human duodenal mucosa and human blood leukocytes at hydrolysing the
      compounds. The rank order of the compounds was, however, very similar in the
      different biological systems. Commercially available pig liver carboxyl esterase
      and cholesterol esterase both reasonably well predict the rank order in the
      tissue fractions.

PMID- 9579035
TI  - Synthesis and antihypertensive activity of 4-(diazabicyclo[4.1.0]
      heptenyloxy)benzopyran derivatives and their analogues.
AB  - A series of 3,4-dihydro-3-hydroxy-4-[(5-oxo-3,4-diazabicyclo[4.1.0]hept- 2-en-2
      yl)oxy]-2H-1-benzopyrans and their analogues were synthesized and evaluated on
      potassium channel opening and hypotensive activities. Compound (-)-13B with a (4
      methyl-5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy group for the 4-position
      of the benzopyran ring was 3 times as potent as EMD 57283 (II), the lead
      compound, in hypotensive activity. The results would demonstrate that 5-oxo-3,4
      diazabicyclo[4.1.0]hept-2-en-2-yloxy moieties are effective as the substituents
      at the 4-position of benzopyran-type potassium channel openers.

PMID- 9579036
TI  - A novel histamine 2(H2) receptor antagonist with gastroprotective activity. I.
      Synthesis and pharmacological evaluation of N-phenoxypropylacetamide derivatives
      with thioether function.
AB  - In an attempt to develop new types of anti-ulcer agents, a series of N
      (phenoxypropyl)acetamide derivatives with a thioether moiety and their sulfur
      oxidized analogues were synthesized and evaluated for histamine H2-receptor
      antagonistic activity, Ca antagonistic activity and gastric anti-secretory
      activity in the lumen-perfuseed rat. Selected compounds were also tested for
      gastroprotective activity, which was expected to be based on Ca antagonistic
      activity. Structure-activity relationships are discussed. As a thioether moiety, 
      CH2-S(O)p-CH2-Ar (Ar; phenyl or furyl) was found to be optimal for the above
      activities. Especially, N-[3-[(3-(piperidinomethyl) phenoxy]propyl]acetamide with
      a benzyl sulfinyl, benzylsulfonyl, furfurylsulfinyl or furfurylsulfonyl group
      showed potent gastroprotective activity upon oral administration in a rat model.
      These compounds are candidates for novel anti-ulcer drugs with gastric anti
      secretory and gastroprotective activities. 2-Furfurylsulfinyl-N-[3
      [(piperidinomethyl)phenoxy]propyl]ac etamide was the most potent among the
      compounds tested and was given the code designation FRG-8701.

PMID- 9579038
TI  - Synthesis and antifungal activity of novel thiazole-containing triazole
      antifungals. II. Optically active ER-30346 and its derivatives.
AB  - A series of novel thiazole-containing triazole antifungals was synthesized and
      evaluated for antifungal activity against a variety of clinically isolated
      pathogenic fungi in vitro and against systemic candidosis in vivo. These
      compounds showed potent antifungal activities in vitro and in vivo. In
      particular, (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4- difluorophenyl)-1
      (1H-1,2,4-triazol-1-yl)-2-butanol (12g; ER-30346) showed potent and well-balanced
      in vitro activities and potent in vivo efficacy, and had a good safety profile.

PMID- 9579037
TI  - A novel histamine 2(H2) receptor antagonist with gastroprotective activity. II.
      Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2
      furfurylsulfinyl acetamide derivatives with heteroaromatic rings.
AB  - We recently found that N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide
      derivatives with a thioether function showed gastric anti-secretory and
      gastroprotective activities and that the thioether function (particularly
      furfurylthio or furfurylsulfinyl) was essential for gastroprotection. In the
      present study, a series of 2-furfurylthio and 2-furfurylsulfinyl acetamide
      derivatives were synthesized and evaluated for histamine H2 receptor antagonistic
      activity, gastric anti-secretory activity and gastroprotective action. Based on
      the structure of N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide, we designed
      compounds, in which the 3-(piperidinomethyl)phenoxy part is substituted with many
      types of heteroaromatic ring attached to the tertiary amine and the propyl group
      is replaced with other carbon linkages. Structure-activity relationships are
      discussed. 2-Furfurylsulfinyl-N-[4-[4-(piperidinomethyl)-2-pyridylox y]- (Z)-2
      butenyl]acetamide was the most potent among the tested compounds and was given
      the code designation FRG-8813.

PMID- 9579039
TI  - Synthesis and structure--antibacterial activity relationships of 7-(3-amino-1
      propynyl and 3-amino-1-propenyl)quinolones.
AB  - 7-(3-Amino-1-propynyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4- oxoquinoline-3
      carboxylic acid (7a) and some related compounds (7b-f, 8a, b, 9) were prepared
      via palladium(0)-catalyzed cross-coupling reaction of 7-iodoquinolone 12 with
      acetylenic compounds and their antibacterial activity was tested. The methylene
      homologue (7d) and the N-methyl derivative (7e) of 7a showed essentially the same
      activity as that of 7a. Addition of methyl group(s) to C'-3 of 7a (giving 7b, c)
      reduced the activity. The hydrogenation of 7a to (Z)-3-amino-1-propenyl (8a), (E)
      3-amino-1-propenyl (8b) and 3-amino-1-propyl (9) compounds retained or enhanced
      the activity of 7a. Among the compounds prepared, 8a was the most active, but was
      less active than ciprofloxacin (1). In order to get insight into structure
      activity relationships, the spatial distribution of the amino groups of 7a, 8a,
      b, and 9 was examined by means of computer-aided molecular modeling.

PMID- 9579040
TI  - [2-(omega-phenylalkyl)phenoxy]alkylamines: synthesis and dual dopamine2 (D2) and
      5-hydroxytryptamine2 (5-HT2) receptor antagonistic activities.
AB  - A series of [2-(omega-phenylalkyl)phenoxy]alkylamines was synthesized and their 5
      hydroxytryptamine2 (5-HT2) and/or dopamine2 (D2) receptor antagonistic activities
      were examined in vitro. [2-(4-Phenylbutyl)phenoxy]alkylamines showed strong
      inhibition of both 5-HT2 and D2 receptors. In particular, [2-(4
      Phenylbutyl)phenoxy]-methylpiperidine derivatives, 10b, 10i and 10q, exhibited
      potent inhibition. The structure-activity relationships in this series of
      compounds are discussed.

PMID- 9579042
TI  - Pharmacologically active components of viticis fructus (Vitex rotundifolia). II.
      The components having analgesic effects.
AB  - The extract of Viticis Fructus appeared to have an analgesic effect, and was
      subjected to activity-guided separation using acetic acid-induced writhing in
      mice. The active fraction gave new compounds, vitexfolin A (1A), B and C, 10-O
      vanilloylaucubin (3), dihydrodehydrodiconiferylalcohol-beta-D- (2'-O-p
      hydroxybenzoyl)glucoside (4), and vanilloyl-beta-D-(2'O-p
      hydroxybenzoyl)glucoside, together with agnuside (2) and erythro- and
      threoguaiacylglycerols. Compounds 1A and 2-4 showed significant writhing
      inhibition following oral administration at doses of 15, 50, 25, and 50 mg/kg,
      respectively. The effect on pressure pain threshold was tested using compounds 1A
      and 2 at a dose of 50 mg/kg, and only the former produced the analgesia. The
      analgesic effect of some related iridoid glucosides is also discussed.

PMID- 9579041
TI  - Bioactive saponins and glycosides. XI. Structures of new dammarane-type
      triterpene oligoglycosides, quinquenosides I, II, III, IV, and V, from American
      ginseng, the roots of Panax quinquefolium L.
AB  - The methanolic extract and 1-butanol-soluble fraction of American ginseng, the
      roots of Panax quinquefolium L., were found to exhibit a protective effect on
      liver injury induced by D-galactosamine and lipopolysaccharide. Five new
      dammarane-type triterpene oligoglycosides called quinquenosides I, II, III, IV,
      and V were isolated together with fourteen known dammarane-type triterpene
      oligoglycosides such as chikusetsusaponin IVa, pseudo-ginsenoside-RC1, malonyl
      ginsenoside-Rb1, and notoginsenosides-A,-C, and -K from the 1-butanol-soluble
      fraction. From the ethyl acetate-soluble fraction, four known acetylenic
      compounds and 6'-O-acetyl ginsenoside-Rg1 were isolated. The structures of
      quinquenosides I, II, III, IV, and V were determined on the basis of chemical and
      physicochemical evidence as 3-O-[6-O-(E)-2-butenoyl-beta-D-glucopyranosyl(1-->2)
      beta-D- glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol
      (quinquenoside I), 3-O-[6-O-(E)-2-octenoyl-beta-D- glucopyranosyl(1-->2)-beta-D
      glucopyranosyl]-20-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] 20(S)
      protopanaxadiol (quinquenoside II), 3-O-[beta-D-glucopyranosyl (1-->2)-6-O-acetyl
      beta-D-glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol
      (quinquenoside III), 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20
      O-beta-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl]-3 beta, 7 beta, 20(S)
      trihydroxydammar-5,24-diene (quinquenoside IV), and 3-O-[beta-D-glucopyranosyl(1-
      >2)-beta-D-glucopyranosyl]-20-O-[alpha-D- glucopyranosyl(1-->4)-beta-D
      glucopyranosyl(1-->6)-beta-D-glucopyranosyl ] 20(S)-protopanaxadiol
      (quinquenoside V).

PMID- 9579043
TI  - Mechanochemical solid-state polymerization. VIII. Novel composite polymeric
      prodrugs prepared by mechanochemical polymerization in the presence of
      pharmaceutical aids.
AB  - We carried out the mechanochemical polymerization of methacryloyl derivatives of
      acetoaminophen and 5-fluorouracil in the presence of lactose. The reaction
      proceeded readily and the polymeric prodrugs were quantitatively produced. This
      method produces powdered polymeric prodrugs in which fine particles of lactose
      are homogeneously dispersed, since the reaction proceeds quantitatively through a
      totally dry process. It is difficult to prepare such a powdered polymeric prodrug
      by conventional solution polymerization. The rate of drug release of polymeric
      prodrugs increases with increasing content of lactose, as is shown to be true of
      the specific surface of polymeric prodrugs. These results suggest that lactose is
      homogeneously dispersed in powdered polymeric prodrugs. The present method seems
      applicable to a wide variety of pharmaceutical aids. If one takes the
      physiochemical property of pharmaceutical aids into consideration, novel
      polymeric prodrugs with a variety of drug release rates can be synthesized
      simultaneously with mixing.

PMID- 9579044
TI  - Sulfoquinovosyldiacylglycerol, KM043, a new potent inhibitor of eukaryotic DNA
      polymerases and HIV-reverse transcriptase type 1 from a marine red alga,
      Gigartina tenella.
AB  - A new sulfolipid, KM043, which belongs to the 6-sulfo-alpha-D-quinovopyranosyl-(1
      ->3')-1',2'-diacylglycerol (SQDG) class of compounds, has been isolated from a
      marine red alga, Gigartina tenella, as a potent inhibitor of eukaryotic DNA
      polymerases and HIV-reverse transcriptase type 1. Its structure was determined on
      the basis of spectroscopic and gas chromatographic analyses. The inhibition was
      dose-dependent, and complete (more than 90%) inhibition of DNA polymerase alpha
      (pol. alpha), DNA polymerase beta (pol. beta) and HIV-reverse transcriptase type
      1 (HIV-RT) was observed at concentrations of 5, 10, and 30 microM, respectively.

PMID- 9579045
TI  - Syntheses of HIV-protease inhibitors having a peptide moiety which binds to
      GP120.
AB  - Some HIV-protease inhibitor derivatives having an N-carbomethoxycarbonyl-prolyl
      phenylalanine benzyl ester (CPF) moiety as a binding site to gp120 were designed
      and synthesized. Almost all the compounds bearing CPF on the phenoxyacetyl group
      showed protease-inhibitory activity. Compounds 25a and 25b, which have the CPF
      moiety at the ortho- and meta-positions of the phenoxyacetyl group, respectively,
      had anti-HIV activity, although the others showed only protease-inhibitory
      activity. These results suggest that 25b binds to gp120 and inhibits HIV
      protease.

PMID- 9579046
TI  - A general approach to the synthesis of polyamine linked-monoindolylmaleimides, a
      new series of trypanothione reductase inhibitors.
AB  - A simplified approach to the synthesis of 2-polyamine linked
      monoindolylmaleimides has been achieved, leading to a new series of trypanothione
      reductase inhibitors. The conditions of access to N,2-bis(polyamine)-3
      monoindolylmaleimides and N,N'-bis(monoindolylmaleimide) polyamines are
      described. Measured inhibitory activities towards trypanothione reductase from
      Tryanosoma cruzi show the importance of both aromatic moieties and polyamine
      chains for trypanothione reductase recognition.

PMID- 9579047
TI  - Synthesis and evaluation of the CNS activity of new 4-alkoxyphenylimidazolidin-2
      ones.
AB  - Various 4-alkoxyphenylimidazolidin-2-ones were prepared from benzaldehydes via a
      Curtius rearrangement and were evaluated for their anticonvulsant activities.

PMID- 9579048
TI  - Screening system for urease inhibitors using 13C-NMR.
AB  - Urease inhibitors are candidate drugs to treat infection with the human pathogen,
      Helicobacter pylori, which produces a potent urease [urea amidohydrolase; EC
      3.5.1.5]. We developed a screening system based on 13C-NMR measurement of the
      time course of decrease in the signal of 13C-urea in the presence of urease. The
      effect on urease activity of known inhibitors, hydroxamic acids, L-ascorbic acid,
      2,2'-dipyridyl disulfide and ninhydrin, was speedily and conveniently measured by
      this method.

PMID- 9579049
TI  - Studies on the constituents of Calliandra anomala (Kunth) Macbr. IV. Structure
      analysis by HPLC retention time and FAB-MS spectrum.
AB  - Three new triterpenoidal saponins were isolated from the branches of Calliandra
      anomala (KUNTH) MACBR. On elucidation of their structures, we noticed
      correlations between a series of structures and their HPLC retention time. By
      this behavior and the FAB-MS spectrum, the structures of three saponins
      (calliandra saponin M, N and O) were established.

PMID- 9579050
TI  - A new phenylethanoid glycoside from Phlomis pungens Willd. var. pungens.

PMID- 9579051
TI  - Formation of water-insoluble gel in dry-coated tablets for the controlled release
      of theophylline.
AB  - Sodium alginate (ALNa) of a natural polysaccharide is known to form a water
      insoluble gel when combined with a bivalent metal. In this study, we prepared
      tablets containing ALNa and calcium gluconate (GLCa) as a bivalent metal, and
      studied the application of the water-insoluble gel involving the controlled
      release of a test drug by permeation of water. Dry-coated tablets containing
      theophylline (TP) as a model drug, ALNa and GLCa were prepared by the dry power
      compression method. The controlled release of TP was evaluated by the dissolution
      test according to JP XIII. The release rate was extremely high for the tablets
      which contained only TP and GLCa. A zero order or sigmoidal release profile was
      observed for the tablets that contained only TP and ALNa. On the other hand, the
      lowest dissolution rate and a sigmoidal release profile were observed for the
      tablet containing TP and GLCa in its core and ALNa in its outer phase. These
      results suggest that dry-coated tablets containing ALNa and GLCa and prepared by
      the direct powder compression method would be useful for the controlled release
      of drugs.

PMID- 9579052
TI  - Practical synthesis of (2s,3s)-3-amino-2-hydroxy-4-phenylbutyric acid, a key
      component of HIV protease inhibitors.

PMID- 9579053
TI  - Transformation of peripheral inputs by the first-order lateral line brainstem
      nucleus.
AB  - Extracellular recording techniques were used to record the responses of medial
      nucleus cells and posterior lateral line nerve fibers in mottled sculpin, Cottus
      bairdi, and goldfish, Carassius auratus, to a 50-Hz dipole source (vibrating
      sphere). Responses were characterized in terms of (1) receptive fields that
      relate responsiveness (spike rate and phase-locking) to the location of the
      source along the length of the fish, (2) input-output functions that relate
      responsiveness to vibration amplitude for a fixed source location, and (3) peri
      stimulus time histograms that relate responsiveness to time during a sustained
      period of vibration. Relative to posterior lateral line nerve fibers, medial
      nucleus cells in both species were similar in showing (1) lower spontaneous and
      evoked rates of spike activity, (2) greater degrees of adaptation, (3) greater
      heterogeneity in all response characteristics, and (4) evidence for
      inhibitory/excitatory interactions. Whereas receptive fields of nerve fibers in
      both species faithfully reflect both pressure gradient amplitudes (with rate
      changes) and directions (with phase-angle changes) in the stimulus field,
      receptive fields of medial nucleus were more difficult to relate to the stimulus
      field, Some, but not all, receptive fields could be modeled with excitatory
      center/inhibitory surround and inhibitory center/excitatory surround
      organizations.

PMID- 9579054
TI  - Effect of background components on spatial-frequency masking.
AB  - Previous studies of spatial-frequency masking and adaptation have shown that the
      contrast-detection threshold elevates maximally when the test spatial frequency
      is the same as the masking (or adapting) frequency but changes only slightly when
      they are separated by two or more octaves. At low spatial frequencies, however,
      the peak of the threshold-elevation function does not obey this rule: there is a
      well-established peak shift in the threshold-elevation functions toward higher
      spatial frequencies. We investigated whether this shift might be due to the
      masking effects caused by the background field, which contributes energy at the
      very low end of the spectrum. We first measured the effect of a 3-cycles/deg
      (c/deg) mask on detection of a range of test frequencies, compared with unmasked
      detection thresholds. We then measured the combined effect of a 2-c/deg and a 3
      c/deg mask on detection, compared with detection with just the 2-c/deg mask. The
      comparison in the second case still tests the effect of the 3-c/deg mask, but the
      presence of the hidden 2-c/deg mask causes the peak masking effect to shift
      toward higher frequencies. This result provides a proof of concept for the
      hypothesis that the peak shift at low spatial frequencies is caused by the low
      frequency energy in the background field, which is present in both masked and
      unmasked conditions. A five-parameter quantitative model of frequency masking is
      presented that describes the pure contrast-detection function, the frequency
      masking functions at mask frequencies of 0.25, 0.5, 2, and 3 c/deg, and the peak
      shift phenomenon.

PMID- 9579055
TI  - Developments in generalized ranked-order filters.
AB  - A general formulation of ranked-order filters is developed in two parts: part 1,
      signal-to-noise-ratio analysis and part 2, construction and analysis of a ranked
      order-filter function based on a mathematical logic approach. The filter function
      is analyzed to define the structure of filter roots for one-dimensional (1-D) and
      two-dimensional (2-D) window filters as data patterns that are invariant of the
      filter. The 1-D and 2-D coded window filters defined for roots of repeated
      patterns of binary data are defined and analyzed. The analysis concludes with an
      application of the coded window filter to a computer-generated 2-D noisy image
      containing a binary pattern and an application for feature extraction by a 2-D
      filter constrained by a predicate function to select only fixed-point root data
      structures.

PMID- 9579056
TI  - Bounds on null functions of linear digital imaging systems.
AB  - Any linear digital imaging system produces a finite amount of data from a
      continuous object. This means that there are always null functions, so a
      reconstruction of the object, even without noise in the system, will differ from
      the actual object. With positivity constraints, the size of a null function is
      limited, provided that size is measured by the integral of the absolute value of
      the null function. When smoothing is used in reconstruction, then smoothed null
      functions become relevant. There are bounds on various measures of the size of
      smoothed null functions, and these bounds can be quite small. Smoothing will
      decrease the effects of null functions in object reconstructions, and this effect
      is greater if the smoothing operator is well matched to the system operator.

PMID- 9579057
TI  - Image analysis of the morphology of filamentous micro-organisms.

PMID- 9579058
TI  - Candida dubliniensis: phylogeny and putative virulence factors.
AB  - Candida dubliniensis is a recently identified species which is implicated in oral
      candidosis in HIV-infected and AIDS patients. The species shares many phenotypic
      characteristics with, and is phylogenetically closely related to, Candida
      albicans. In this study the phylogenetic relationship between these two species
      was investigated and a comparison of putative virulence factors was performed.
      Four isolates of C. dubliniensis from different clinical sources were chosen for
      comparison with two reference C. albicans strains. First, the distinct
      phylogenetic position of C. dubliniensis was further established by the
      comparison of the sequence of its small rRNA subunit with representative Candida
      species. The C. dubliniensis isolates formed true unconstricted hyphae under most
      induction conditions tested but failed to produce true hyphae when induced using
      N-acetylglucosamine. Oral C. dubliniensis isolates were more adherent to human
      buccal epithelial cells than the reference C. albicans isolates when grown in
      glucose and equally adherent when grown in galactose. The C. dubliniensis
      isolates were sensitive to fluconazole, itraconazole, ketoconazole and
      amphotericin B. Homologues of seven tested C. albicans secretory aspartyl
      proteinase (SAP) genes were detected in C. dubliniensis by Southern analysis. In
      vivo virulence assays using a systemic mouse model suggest that C. dubliniensis
      is marginally less virulent than C. albicans. These data further confirm the
      distinct phenotypic and genotypic nature of C. dubliniensis and suggest that this
      species may be particularly adapted to colonization of the oral cavity.

PMID- 9579059
TI  - A Candida albicans 37 kDa polypeptide with homology to the laminin receptor is a
      component of the translational machinery.
AB  - A cDNA encoding a 37 kDa protein was isolated from an expression library using
      antibodies raised against mycelial cell walls from Candida albicans. The 37 kDa
      protein has over 60% sequence identity with the 37 kDa laminin-binding protein
      (LBP) from humans and over 80% identity with the Yst proteins of Saccharomyces
      cerevisiae. The C. albicans protein was named CaYst1. It was found in membrane
      and ribosome fractions but surprisingly, was not found in cell walls. Unlike the
      human LBP, CaYst1p does not bind laminin. These data indicate that CaYst1p is not
      a cell-surface receptor for laminin as has been proposed for the human LBP.
      Instead, like the S. cerevisiae Yst proteins, it appears to be a ribosomal
      protein. This conclusion is supported by the finding that CaYST1-cDNA complements
      the lethal phenotype linked to the disruption of both YST genes in S. cerevisiae.

PMID- 9579060
TI  - Repetitive sequences (RPSs) in the chromosomes of Candida albicans are sandwiched
      between two novel stretches, HOK and RB2, common to each chromosome.
AB  - A novel sequence designated HOK, which is next to the RPS, a repetitive sequence
      specific to Candida albicans, was cloned and sequenced. HOK hybridized with all
      of the chromosomes on which the RPSs were located, but did not hybridize with
      chromosome 3, which does not harbour any RPSs. Sequence determination revealed
      that a portion of HOK has significant homology with the B and C1 fragments of
      Ca3, which is used as a molecular epidemiological probe. A homology search of the
      deduced amino acids of HOK against the protein database showed partial homology
      with an isocitrate dehydrogenase of Saccharomyces cerevisiae, although an ORF
      large enough to encode the enzyme was not detected. To verify the existence of
      other sequences homologous with HOK, a portion of the HOK sequence was amplified
      using PCR. Sequence determination of the 41 clones from the PCR products resulted
      in at least six HOK-homologous clones. Another RPS-containing clone, RB2, was
      isolated from the Pstl-digested chromosome R or 1. It was determined that RB2a,
      one of the subclones from RB2, hybridized with all of the chromosomes, including
      chromosome 3, with which neither HOK nor RPS hybridized. The hybridization
      profile also showed that RPS is located between HOK and RB2a on chromosomes other
      than chromosome 3.

PMID- 9579061
TI  - The 172 kb prkA-addAB region from 83 degrees to 97 degrees of the Bacillus
      subtilis chromosome contains several dysfunctional genes, the glyB marker, many
      genes encoding transporter proteins, and the ubiquitous hit gene.
AB  - A 171812 bp nucleotide sequence between prkA and addAB (83 degrees to 97 degrees)
      on the genetic map of the Bacillus subtilis 168 chromosome was determined and
      analysed. An accurate physical/genetic map of this previously poorly described
      chromosomal region was constructed. One hundred and seventy open reading frames
      (ORFs) were identified on the DNA fragment. These include the previously
      described genes cspB, glpPFKD, spoVR, phoAIV, papQ, citRA, sspB, prsA, hpr, pbpF,
      hemEHY, aprE, comK and addAB. ORF yhaF in this region corresponds to the glyB
      marker. Among the striking features of this region are: an abundance of genes
      encoding (putative) transporter proteins, several dysfunctional genes, the
      ubiquitous hit gene, and five multidrug-resistance-like genes. These analyses
      have also revealed the existence of numerous paralogues of ORFs in this region:
      about two-thirds of the putative genes seem to have at least one paralogue in the
      B. subtilis genome.

PMID- 9579062
TI  - A 35.7 kb DNA fragment from the Bacillus subtilis chromosome containing a
      putative 12.3 kb operon involved in hexuronate catabolism and a perfectly
      symmetrical hypothetical catabolite-responsive element.
AB  - The Bacillus subtilis strain 168 chromosomal region extending from 109 degrees to
      112 degrees has been sequenced. Among the 35 ORFs identified, cotT and rapA were
      the only genes that had been previously mapped and sequenced. Out of ten ORFs
      belonging to a single putative transcription unit, seven are probably involved in
      hexuronate catabolism. Their sequences are homologous to Escherichia coli genes
      exuT, uidB, uxaA, uxaB, uxaC, uxuA and uxuB, which are all required for the
      uptake of free D-glucuronate, D-galacturonate and beta-glucuronide, and their
      transformation into glyceraldehyde 3-phosphate and pyruvate via 2-keto-3
      deoxygluconate. The remaining three ORFs encode two dehydrogenases and a
      transcriptional regulator. The operon is preceded by a putative catabolite
      responsive element (CRE), located between a hypothetical promoter and the RBS of
      the first gene. This element, the longest and the only so far described that is
      fully symmetrical, consists of a 26 bp palindrome matching the theoretical B.
      subtilis CRE sequence. The remaining predicted amino acid sequences that share
      homologies with other proteins comprise: a cytochrome P-450, a
      glycosyltransferase, an ATP-binding cassette transporter, a protein similar to
      the formate dehydrogenase alpha-subunit (FdhA), protein similar to NADH
      dehydrogenases, and three homologues of polypeptides that have undefined
      functions.

PMID- 9579063
TI  - The N-acetylmuramoyl-L-alanine amidase encoded by the Bacillus subtilis 168
      prophage SP beta.
AB  - Heat shock of Bacillus subtilis CU1147, a strain lysogenic for SP beta c2, a
      prophage with a thermosensitive repressor, results in phage induction and
      subsequent cell lysis. Cloning in Escherichia coli and sequencing of a DNA
      fragment of prophage SP beta led to the identification of blyA, the gene encoding
      a 367 amino acid polypeptide with a molecular mass of 39.6 kDa. Purified BlyA
      obtained from the E. coli clone exhibited an N-acetylmuramoyl-L-alanine amidase
      activity. Insertional mutagenesis confirmed that the latter enzyme was associated
      with SP beta-phage-mediated cell lysis. Analysis of the neighbouring sequence
      suggested that the two ORFs immediately downstream of blyA and belonging to the
      same operon encode polypeptides which may be involved in the release of the
      endolysin. The presence on the chromosomes of B. subtilis or related Bacillus
      spp. of other, similar genes, and their possible relationship, is discussed.

PMID- 9579064
TI  - An operon encoding three glycolytic enzymes in Lactobacillus delbrueckii subsp.
      bulgaricus: glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and
      triosephosphate isomerase.
AB  - The structural genes gap, pgk and tpi encoding three glycolytic enzymes,
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglycerate kinase (PGK)
      and triosephosphate isomerase (TPI), respectively, have been cloned and sequenced
      from Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus). The genes were
      isolated after screening genomic sublibraries with specific gap and pgk probes
      obtained by PCR amplification of chromosomal DNA with degenerate primers
      corresponding to amino acid sequences highly conserved in GAPDHs and PGKs.
      Nucleotide sequencing revealed that the three genes were organized in the order
      gap-pgk-tpi. The translation start codons of the three genes were identified by
      alignment of the N-terminal sequences. These genes predicted polypeptide chains
      of 338, 403 and 252 amino acids for GAPDH, PGK and TPI, respectively, and they
      were separated by 96 bp between gap and pgk, and by only 18 bp between pgk and
      tpi. The codon usage in gap, pgk, tpi and three other glycolytic genes from L.
      bulgaricus differed, noticeably from that in other chromosomal genes. The site of
      transcriptional initiation was located by primer extension, and a probable
      promoter was identified for the gap-pgk-tpi operon. Northern hybridization of
      total RNA with specific probes showed two transcripts, an mRNA of 1.4 kb
      corresponding to the gap gene, and a less abundant mRNA of 3.4 kb corresponding
      to the gap-pgk-tpi cluster. The absence of a visible terminator in the 3'-end of
      the shorter transcript and the location of this 3'-end inside the pgk gene
      indicated that this shorter transcript was produced by degradation of the longer
      one, rather than by an early termination of transcription after the gap gene.

PMID- 9579065
TI  - Pyruvate carboxylase from Corynebacterium glutamicum: characterization,
      expression and inactivation of the pyc gene.
AB  - In addition to phosphoenolpyruvate carboxylase (PEPCx), pyruvate carboxylase
      (PCx) has recently been found as an anaplerotic enzyme in the amino-acid
      producing bacterium Corynebacterium glutamicum. Using oligonucleotides designed
      according to conserved regions of PCx amino acid sequences from other organisms,
      a 200 bp fragment central to the C. glutamicum PCx gene (pyc) was amplified from
      genomic DNA by PCR. This fragment was then used to identify and to subclone the
      entire C. glutamicum pyc gene. The cloned pyc gene was expressed in C.
      glutamicum, as cells harbouring the gene on plasmid showed four- to fivefold
      higher specific PCx activities when compared to the wild-type (WT). Moreover,
      increased PCx protein levels in the pyc-plasmid-carrying strain were readily
      detected after SDS-PAGE of cell-free extracts. DNA sequence analysis of the pyc
      gene, including its 5' and 3' flanking regions, and N-terminal sequencing of the
      pyc gene product predicts a PCx polypeptide of 1140 amino acids with an M(r) of
      123070. The amino acid sequence of this polypeptide shows between 62% and 45%
      identity when compared to PCx enzymes from other organisms. Transcriptional
      analyses revealed that the pyc gene from C. glutamicum is monocistronic (3.5 kb
      mRNA) and that its transcription is initiated at an A residue 55 bp upstream of
      the translational start. Inactivation of the chromosomal pyc gene in C.
      glutamicum WT led to the absence of PCx activity and to negligible growth on
      lactate, indicating that PCx is essential for growth on this carbon source.
      Inactivation of both the PCx gene and the PEPCx gene in C. glutamicum led
      additionally to the inability to grow on glucose, indicating that no further
      anaplerotic enzymes for growth on carbohydrates exist in this organism.

PMID- 9579066
TI  - Citrate synthase and 2-methylcitrate synthase: structural, functional and
      evolutionary relationships.
AB  - Following the complete sequencing of the Escherichia coli genome, it has been
      shown that the proposed second citrate synthase of this organism, recently
      described by the authors, is in fact a 2-methylcitrate synthase that possesses
      citrate synthase activity as a minor component. Whereas the hexameric citrate
      synthase is constitutively produced, the 2-methylcitrate synthase is induced
      during growth on propionate, and the catabolism of propionate to succinate and
      pyruvate via 2-methylcitrate is proposed. The citrate synthases of the
      psychrotolerant eubacterium DS2-3R, and of the thermophilic archaea Thermoplasma
      acidophilum and Pyrococcus furiosus, are approximately 40% identical in sequence
      to the Escherichia coli 2-methylcitrate synthase and also possess 2-methylcitrate
      synthase activity. The data are discussed with respect to the structure, function
      and evolution of citrate synthase and 2-methylcitrate synthase.

PMID- 9579067
TI  - Physiological function and regulation of flavocytochrome c3, the soluble fumarate
      reductase from Shewanella putrefaciens NCIMB 400.
AB  - Shewanella putrefaciens produces a soluble flavocytochrome c under anaerobic
      growth conditions. This protein shares sequence similarity with the catalytic
      subunits of membrane-bound fumarate reductases from Escherichia coli and other
      bacteria and the purified protein has fumarate reductase activity. It is shown
      here that this enzyme, flavocytochrome c3, is essential for fumarate respiration
      in vivo since disruption of the chromosomal fccA gene, which encodes
      flavocytochrome c3, leads to a specific loss of the ability to grow with fumarate
      as terminal electron acceptor. Growth with nitrate, trimethylamine N-oxide (TMAO)
      and other acceptors was unaffected. The fccA gene is transcribed as a 2 kb
      monocistronic mRNA. An adjacent reading frame that bears limited sequence
      similarity to one of the membrane anchor subunits of E. coli fumarate reductase
      is not co-transcribed with fccA. Expression of the fccA gene is regulated by
      anaerobiosis and by the availability of alternative electron acceptors,
      particularly nitrate and TMAO. DNA sequences have been identified that are
      required for this regulation.

PMID- 9579068
TI  - Efficient conversion of 5-substituted hydantoins to D-alpha-amino acids using
      recombinant Escherichia coli strains.
AB  - D-Amino acids, important intermediates in the production of semisynthetic
      penicillins and cephalosporins, are currently prepared from the corresponding
      hydantoins using bacterial biomass containing two enzymes, hydantoinase and
      carbamylase. These enzymes convert the hydantoins first into carbamyl derivatives
      and then into the corresponding D-amino acids. In an attempt to select more
      efficient biocatalysts, the hydantoinase and carbamylase genes from Agrobacterium
      tumefaciens (formerly A. radiobacter) were cloned in Escherichia coli. The genes
      were assembled to give two operon-type structures, one having the carbamylase
      gene preceding the hydantoinase gene and the other with the carbamylase gene
      following the hydantoinase gene. The recombinant strains stably and
      constitutively produced the two enzymes and efficiently converted the
      corresponding hydantoins into p-hydroxyphenylglycine and phenylglycine. The order
      of the genes within the operon and the growth temperature of the strains turned
      out to be important for both enzyme and D-amino acid production. The
      configuration with the carbamylase gene preceding the hydantoinase gene was the
      most efficient one when the biomass was grown at 25 degrees C rather than 37
      degrees C. This biomass produced D-amino acid twice as efficiently as the
      industrial strain of A. tumefaciens. The efficiency was found to be correlated
      with the level of carbamylase produced, indicating that the concentration of this
      enzyme is the rate-limiting factor in D-amino acid production under the
      conditions used on an industrial scale.

PMID- 9579069
TI  - Cloning of new Rhodococcus extradiol dioxygenase genes and study of their
      distribution in different Rhodococcus strains.
AB  - Four extradiol dioxygenase genes which encode enzymes active against catechol and
      substituted catechols were cloned from two different Rhodococcus strains, and
      their nucleotide sequences were determined. A catechol 2,3-dioxygenase gene
      (edoC) was shown to be identical to the previously described ipbC gene from the
      isopropylbenzene operon of Rhodococcus erythropolis. Amino acid sequences deduced
      from the three other genes (edoA, edoB and edoD) were shown to have various
      degrees of homology to different extradiol dioxygenases. The EdoA and EdoB
      dioxygenases were classified as belonging to the third family of type I
      oxygenases and represented two new subfamilies, whereas the EdoD dioxygenase was
      a type II enzyme. Analysis of six Rhodococcus strains revealed a wide
      distribution of the above dioxygenase genes. Rhodococcus sp. 11 was shown to
      harbour all four of the analysed dioxygenase genes. Nucleotide sequences
      homologous to the edoB gene were present in all of the strains, including R.
      erythropolis NCIMB 13065, which did not utilize any of the aromatic compounds
      analysed. The latter finding points to the existence of a silent pathway(s) for
      degradation of aromatic compounds in this Rhodococcus strain.

PMID- 9579070
TI  - Genetics of ferulic acid bioconversion to protocatechuic acid in plant-growth
      promoting Pseudomonas putida WCS358.
AB  - Transposon Tn5 genomic mutants of plant-growth-promoting Pseudomonas putida
      strain WCS358 have been isolated which no longer utilize ferulic and coumaric
      acids as sole sources of carbon and energy. Genetic studies confirmed previous
      biochemical data showing that ferulic acid is degraded via vanillic acid, and
      coumaric acid via hydroxybenzoic acid. The genes involved in these enzymic steps
      were cloned and characterized. Two proteins designated Fca (26.5 kDa) and Vdh
      (50.3 kDa) were identified as responsible for the conversion of ferulic acid to
      vanillic acid; the proteins are encoded by the fca and vdh genes which are
      organized in an operon structure in the chromosome. The Vdh protein is 69%
      identical at the amino acid level to the Vdh protein recently identified in
      Pseudomonas sp. strain HR199 and converts vanillin to vanillic acid. Homology
      studies revealed that the Vdh proteins exhibited significant identity to aldehyde
      dehydrogenases from different organisms whereas Fca belonged to the enoyl-CoA
      hydratase family of proteins. Two proteins, designated VanA (39.9 kDa) and VanB
      (34.3 kDa), encoded by two genes, vanA and vanB, are organized in an operon in
      the chromosome. They were found to be responsible for the demethylation of
      vanillic acid to protocatechuic acid. The VanA proteins showed no homology to any
      other known protein, while VanB belonged to the ferredoxin family of proteins.
      This two-component enzyme system demethylated another phenolic monomer, veratric
      acid, thus indicating broad specificity. Studies of the regulation of the vanAB
      operon demonstrated that the genes were induced by the substrate, vanillic acid;
      however, the strongest induction was observed when cells were grown in the
      presence of the product of the reaction, protocatechuic acid.

PMID- 9579072
TI  - A second IgG-binding protein in Staphylococcus aureus.
AB  - Most strains of Staphylococcus aureus express IgG-binding activity and this
      binding has been considered to be solely mediated by protein A. However, the
      existence of a second gene in S. aureus strain 8325-4 encoding an IgG-binding
      polypeptide was recently reported. This novel IgG-binding polypeptide was found
      after panning a shotgun phage display library, made from chromosomal DNA, against
      immobilized human IgG. The complete gene (sbi) encoding this novel IgG-binding
      protein, denoted protein Sbi, has now been cloned and sequenced. Analysis of
      other S. aureus strains showed that this gene is not unique for strain 8325-4.
      The protein consists of 436 amino acids and exhibits an immunoglobulin-binding
      specificity similar to protein A. Furthermore, it is shown that Sbi is highly
      expressed in strain Newman 4, which shows that IgG-binding activity in S. aureus
      can be mediated by proteins other than protein A.

PMID- 9579071
TI  - Comparative analysis of Pseudomonas aeruginosa penicillin-binding protein 7 in
      the context of its membership in the family of low-molecular-mass PBPs.
AB  - The Pseudomonas aeruginosa pbpG gene encoding penicillin-binding protein 7, a
      homologue of the Escherichia coli gene encoding a DD-endopeptidase, was cloned
      and sequenced, pbpG was located immediately downstream of the phenylalanine
      hydroxylase (phh) operon. DNA sequencing revealed an open reading frame of 936 bp
      (starting with a GTG codon) which encodes a protein of 34,115 Da. N-terminal
      amino acid sequencing confirmed the presence of a cleavable N-terminal signal
      peptide of 23 amino acids. Verification that the protein is a penicillin-binding
      protein was directly demonstrated by labelling with 125I-labelled penicillin X.
      Inactivation of P. aeruginosa pbpG by interposon mutagenesis resulted in no
      obvious phenotypic changes, but when P. aeruginosa PbpG was overexpressed in E.
      coli using a T7 expression system, cell lysis resulted. P. aeruginosa PbpG
      resembled E. coli PbpG in being associated with the membrane fraction. Two
      additional members of the PbpG subfamily were identified in the database. P.
      aeruginosa PbpG shows 63% identity with E. coli penicillin-binding protein 7
      (PbpG) and 60% identity with Vibrio cholerae PbpG, but only 23% identity with
      Haemophilus influenzae PbpG. The PbpG subfamily and three other subfamilies
      constituting the low-molecular-mass PBP protein family were analysed by multiple
      alignment of 26 sequences. PbpG exhibited the consensus motifs of other
      penicillin-binding proteins. Ten anchor residues were identified that are
      conserved at the family level within the superfamily of serine-active-site
      penicillin-interacting proteins.

PMID- 9579073
TI  - Affinity purification and characterization of a fibrinogen-binding protein
      complex which protects mice against lethal challenge with Streptococcus equi
      subsp. equi.
AB  - Cell-wall-associated proteins from Streptococcus equi subsp. equi, the causative
      agent of strangles, were analysed with a view to identifying a potential
      protective antigen. Preparations of these proteins, isolated from mutanolysin
      extracts of cell walls, were shown to contain one major high-M(r) protein species
      (apparent M(r) 220,000 and 550,000 when analysed by SDS-PAGE and gel-filtration
      chromatography, respectively). The high-M(r) protein bound horse fibrinogen and
      was purified under non-denaturing conditions using fibrinogen affinity
      chromatography. The fibrinogen-binding protein (FgBP) reacted with serum taken
      from horses recovering from strangles and protected mice against lethal challenge
      from S. equi subsp. equi. The sequence of the corresponding gene (fbp) was
      determined and shown to encode a mature protein (M(r) 54,597) with predicted
      coiled-coil structure. An FgBP truncate, lacking the C-terminal cell
      wall/membrane anchor domain, was overexpressed in and purified from Escherichia
      coli and was shown to behave in an analogous fashion to the wild-type product in
      terms of M(r) estimation, fibrinogen binding and seroreactivity.

PMID- 9579074
TI  - The Staphylococcus aureus and Staphylococcus epidermidis transferrin-binding
      proteins are expressed in vivo during infection.
AB  - Staphylococci express a 42 kDa cell-wall-associated protein which functions as a
      receptor for the mammalian iron-binding glycoprotein transferrin. To determine
      whether this transferrin-binding protein (TBP) is expressed during infection,
      Staphylococcus aureus and Staphylococcus epidermidis were grown in vivo in
      chambers implanted intraperitoneally in rats. SDS-PAGE and Western blotting of
      cell wall proteins prepared from staphylococci recovered directly from the
      chambers revealed the presence of both the TBP and bacterial-surface-associated
      rat transferrin. To obtain evidence for the in vivo expression of the
      staphylococcal TBPs in humans, sera and human peritoneal dialysate (HPD) from non
      infected patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and
      sera from healthy human volunteers were screened for anti-TBP antibodies. Western
      immunoblots revealed that three out of ten samples from the latter group, seven
      out of ten HPD samples and ten of ten CAPD patient serum samples contained
      antibodies to the TBP of both S. aureus and S. epidermidis. To gain further
      insights into the appearance of TBP antibodies, HPD samples were collected over
      time from CAPD patients whose HPD samples taken immediately after catheter
      insertion lacked anti-TBP antibodies. In two of these patients, each of whom
      experienced an episode of peritonitis due to S. epidermidis or Staphylococcus
      hominis, antibodies to the TBP appeared in the HPD collected immediately post
      infection. To determine whether such TBP antibodies were capable of blocking
      interactions between transferrin and its staphylococcal receptor, HPD
      immunoglobulin fractions were purified using protein A-Sepharose beads. In
      competition assays, these immunoglobulins blocked the binding of 125I-labelled
      transferrin both to whole bacteria and to the isolated 42 kDa TBPs of S. aureus
      and S. epidermidis. These provide evidence to show that staphylococcal TBPs are
      expressed in vivo during infection.

PMID- 9579075
TI  - The rrs (16S)-rrl (23S) ribosomal intergenic spacer region as a target for the
      detection of Haemophilus ducreyi by a heminested-PCR assay.
AB  - The intergenic spacer region between the rrs and rrl ribosomal RNA genes of
      Haemophilus ducreyi was analysed and the DNA sequence was used for the selection
      of specific PCR primers. A highly sensitive and specific heminested-PCR assay for
      the identification of H. ducreyi was developed. The assay showed a sensitivity of
      96% on genital ulcer specimens from patients with clinically diagnosed chancroid,
      compared with a sensitivity of 56% for culture methods. These results indicate
      that this PCR assay has the potential to become an accurate and easy reference
      method for the detection of H. ducreyi.

PMID- 9579076
TI  - Carbapenems as inhibitors of OXA-13, a novel, integron-encoded beta-lactamase in
      Pseudomonas aeruginosa.
AB  - A clinical Pseudomonas aeruginosa strain, PAe391, was found to be resistant to a
      number of antibiotics including ticarcillin, piperacillin, cefsulodin and
      amikacin, and a disk diffusion assay showed evidence of pronounced synergy
      between imipenem and various beta-lactam antibiotics. Cloning and nucleotide
      sequence analysis revealed the dicistronic arrangement of an aac(6')-Ib variant
      and a novel blaOXA-type gene between the intI and qacE delta 1 genes typical of
      integrons, in PAe391, this integron was apparently chromosome-borne. The beta
      lactamase, named OXA-13, displayed nine amino acid changes with respect to OXA
      10:I in position 10 of OXA-10 to T (I10T), G20S, D55N, N73S, T107S, Y174F, E229G,
      S245N and E259A, OXA-13 (pIapp = 8.0) showed poor catalytic activity against
      penicillins as well as cephalosporins, but was efficient in hydrolysing some
      penicillinase-resistant beta-lactams, such as cefotaxime and aztreonam. It was
      efficiently inhibited by imipenem (KIapp = 11 nM), and formed a stable complex.
      While the KIapp value of meropenem was similar (16 nM), the corresponding complex
      was less stable.

PMID- 9579077
TI  - Oligopeptide permease in Borrelia burgdorferi: putative peptide-binding
      components encoded by both chromosomal and plasmid loci.
AB  - To elucidate the importance of oligopeptide permease for Borrelia burgdorferi,
      the agent of Lyme disease, a chromosomal locus in B. burgdorferi that encodes
      homologues of all five subunits of oligopeptide permease has been identified and
      characterized. B. burgdorferi has multiple copies of the gene encoding the
      peptide-binding component, OppA; three reside at the chromosomal locus and two
      are on plasmids. Northern analyses indicate that each oppA gene is independently
      transcribed, although the three chromosomal oppA genes are also expressed as bi-
      and tri-cistronic messages. Induction of one of the plasmid-encoded oppA genes
      was observed following an increase in temperature, which appears to be an
      important cue for adaptive responses in vivo. The deduced amino acid sequences
      suggest that all five borrelial oppA homologues are lipoproteins, but the
      protease-resistance of at least one of them in intact bacteria is inconsistent
      with outer-surface localization. Insertional inactivation of a plasmid-encoded
      oppA gene demonstrates that it is not essential for growth in culture.

PMID- 9579078
TI  - The cadmium-stress stimulon of Escherichia coli K-12.
AB  - The influence of cadmium on stress protein production in Escherichia coli K-12
      (strain MG1655) was analysed using two-dimensional polyacrylamide gel
      electrophoresis and the gene-protein database of E. coli K-12. Cadmium (273
      microM) caused complete but transient inhibition of growth accompanied by the
      synthesis of cadmium-induced proteins (CDPs). It was found that some CDPs induced
      during the growth-arrested phase belong to the heat-shock, oxidation stress, SOS
      and stringent response regulons, while others are general stress inducible
      proteins (e.g. H-NS, UspA). In addition, trigger factor, adenylate kinase, W
      protein, the cold shock protein G041.2, and seven unknown proteins whose
      synthesis is not known to be controlled by a global regulator, were identified as
      immediate responders to cadmium exposure. The rate of synthesis of most of the
      immediate responders to cadmium exposure decreased when the growth of the cells
      resumed. However, seven CDPs, including those encoded by argI, tyrA and xthA,
      maintained a high production rate during growth in the presence of cadmium. Two
      of the unidentified proteins were N-terminally sequenced by Edman degradation.
      The N-terminal amino acid sequence of one of these proteins (designated F023.3)
      matches the E. coli open reading frame o216. This ORF is similar to the N
      terminal third of the copper-binding protein amine oxidases (encoded by maoA) of
      both E. coli and Klebsiella pneumoniae (K. aerogenes). The other N-terminally
      sequenced protein (designated C044.6) matches perfectly the product of the metK
      gene, S-adenosylmethionine synthetase I. In comparison to untreated cells,
      cadmium-stressed cells were found to recover more rapidly during subsequent
      stress conditions, such as ethanol, osmotic, heat shock, and nalidixic acid
      treatment. The role of the CDPs is discussed in view of their physiological
      assignments in the cell.

PMID- 9579079
TI  - Tandem organization and highly disparate expression of the two laccase genes lcc1
      and lcc2 in the cultivated mushroom Agaricus bisporus.
AB  - Two non-allelic laccase genes (lcc1 and lcc2) in Agaricus bisporus have been
      mapped to the same cosmid clone and are close together, in tandem. The intergenic
      region consists of 1562 bp between the stop codon of lcc1 and the start codon of
      lcc2. Differences between the 5' non-coding regions of the two genes suggest the
      potential for their differential regulation. By employing competitive RT-PCR and
      specific primer pairs that discriminate between lcc1 and lcc2, it has been shown
      that the level of lcc2 mRNA is approximately 300 times higher than that of lcc1
      mRNA in malt extract liquid cultures; in compost cultures lcc2 mRNA is almost
      7000 times more abundant than lcc1 mRNA.

PMID- 9579080
TI  - Molecular analysis of Physarum haemagglutinin I: lack of a signal sequence,
      sulphur amino acids and post-translational modifications.
AB  - The cDNAs encoding haemagglutinin I from plasmodia of Physarum polycephalum have
      been cloned using PCR protocols. The composite haemagglutinin I cDNA sequence,
      derived from several overlapping clones from PCR fragments, spans 408 nt and the
      315 bp ORF encodes a polypeptide of 104 aa without a typical signal sequence. The
      putative molecular mass deduced from the amino acid sequence (10,760.76 Da)
      corresponds exactly to that determined by electrospray ionization MS (10,759.86
      +/- 0.15 Da), suggesting that haemagglutinin I is not subject to post
      translational modification. Haemagglutinin I lacks sulphur amino acids and has a
      beta-sheet as the major secondary structure. Expression of the coding sequence in
      Escherichia coli yielded a product that exhibits the same sugar-binding
      specificity as natural haemagglutinin I. The deduced amino acid sequence shows
      little similarity to that of any known lectins and thus apparently represents a
      novel type of lectin.

PMID- 9579081
TI  - Identification of a CAP (adenylyl-cyclase-associated protein) homologous gene in
      Lentinus edodes and its functional complementation of yeast CAP mutants.
AB  - The adenylyl-cyclase-associated protein, CAP, was originally identified in yeasts
      as a protein that functions in both signal transduction and cytoskeletal
      organization. This paper reports the identification of a cDNA and genomic DNA
      that encodes a CAP homologue from the mushroom Lentinus edodes. The L. edodes cap
      gene contains eight introns and an ORF encoding a 518 amino acid protein. The L.
      edodes CAP is 35.5% and 40.9% identical at the amino acid level with
      Saccharomyces cerevisiae CAP and Schizosaccharomyces pombe CAP, respectively. The
      C-terminal domain shows greater homology (39-46% identity) with yeast CAPs than
      does the N-terminal domain (27-35% identity). Southern blotting and Northern
      blotting results suggest that L. edodes cap is a single-copy gene and uniformly
      expressed. Expression of the L. edodes CAP in both Schiz. pombe and Sacch.
      cerevisiae complemented defects associated with the loss of the C-terminal domain
      function of the endogenous CAP. By using a yeast two-hybrid assay, an interaction
      was demonstrated between the L. edodes CAP and Schiz. pombe actin. This result
      and the functional complementation test indicate that CAP from L. edodes has a
      conserved C-terminal domain function.

PMID- 9579082
TI  - D-amino-acid oxidase gene from Rhodotorula gracilis (Rhodosporidium toruloides)
      ATCC 26217.
AB  - The complete nucleotide sequence of the DAO1 gene encoding D-amino-acid oxidase
      (DAAO) in the yeast Rhodotorula gracilis (Rhodosporidium toruloides) ATCC 26217
      has been determined. The primary structure of DAAO was deduced from the
      nucleotide sequence of a cDNA clone that covered the entire amino acid coding
      sequence. Comparison of cDNA and genomic sequences of DAO1 revealed the presence
      of five introns. Because this is the first gene of strain ATCC 26217 that has
      been cloned so far, the nucleotide sequences of these introns were compared to
      those from other fungi. Upstream of the structural gene there was a stretch of C
      + T-rich DNA similar to that found in the promoter region of a number of yeast
      genes. The cDNA gene, which encoded a protein of 368 amino acids (molecular mass
      40 kDa), was overexpressed in Escherichia coli under the control of the strong
      lipoprotein promoter. Interestingly, a significant fraction (13-62%) of the total
      DAAO activity was recovered in its apoenzyme form, the percentage depending on
      the culture conditions. This fact allowed a rapid purification of the recombinant
      DAAO by affinity chromatography. The high level of expression achieved in E. coli
      and the possibility of modifying its catalytic properties by protein engineering
      provide a new model for the study of this enzyme.

PMID- 9579083
TI  - Lack of correlation between trehalose accumulation, cell viability and
      intracellular acidification as induced by various stresses in Saccharomyces
      cerevisiae.
AB  - A pma1-1 mutant of Saccharomyces cerevisiae with reduced H(+)-ATPase activity and
      the isogenic wild-type strain accumulated high levels of trehalose in response to
      a temperature upshift to 40 degrees C and after addition of 10% ethanol, but only
      modest levels in response to a rapid drop in external pH and after addition of
      decanoic acid. There was, however, no correlation between the absolute levels of
      trehalose in the stressed cells and their viability. All these treatments induced
      a significant decrease in intracellular pH, and surprisingly, this decrease was
      very similar in both strains, indicating that intracellular acidification could
      not be the triggering mechanism for trehalose accumulation in response to stress.
      A careful investigation of metabolic parameters was carried out to explain how
      trehalose accumulated under the four different stress conditions tested. No
      single and common mechanism for trehalose accumulation could be put forward and
      the transcriptional activation of TPS1 was not unequivocally related to trehalose
      accumulation. Another finding was that a pma1-1 mutant exhibited a two- to
      threefold greater capacity to accumulate trehalose than the isogenic wild-type.
      This enhanced disaccharide synthesis could be attributed to a twofold higher
      trehalose-6-phosphate synthase activity, together with a fourfold higher content
      of intracellular UDP-Glc. In addition, this mutant showed 1.5-fold higher levels
      of ATP compared to the wild-type. The various stress treatments studied showed
      that a drop in intracellular pH does not correlate with trehalose accumulation.
      It is suggested that plasma membrane alteration could be the physiological
      trigger inducing trehalose accumulation in yeast.

PMID- 9579084
TI  - Fructose and mannose metabolism in Aeromonas hydrophila: identification of
      transport systems and catabolic pathways.
AB  - Aeromonas hydrophila was examined for fructose and mannose transport systems. A.
      hydrophila was shown to possess a phosphoenolpyruvate (PEP): fructose
      phosphotransferase system (fructose-PTS) and a mannose-specific PTS, both induced
      by fructose and mannose. The mannose-PTS of A. hydrophila exhibited cross
      reactivity with Escherichia coli mannose-PTS proteins. The fructose-PTS proteins
      exhibited cross-reactivities with E. coli and Xanthomonas campestris fructose-PTS
      proteins. In A. hydrophila grown on mannose as well as on fructose, the
      phosphorylated derivative accumulated from fructose was fructose 1-phosphate.
      Identification of fructose 1-phosphate was confirmed by 13C-NMR spectroscopy. 1
      Phosphofructokinase (1-PFK), which converts the product of the PTS reaction to
      fructose 1,6-diphosphate, was present in A. hydrophila grown with fructose but
      not on mannose. An inducible phosphofructomutase (PFM) activity, an unusual
      enzyme converting fructose 1-phosphate to fructose 6-phosphate, was detected in
      extracts induced by mannose or fructose. These results suggest that in cells
      grown on fructose, fructose 1-phosphate could be converted to fructose 1,6
      diphosphate either directly by the 1-PFK activity or via fructose 6-phosphate by
      the PFM and 6-phosphofructokinase activities. In cells grown on mannose, the
      degradation of fructose 1-phosphate via PFM and the Embden-Meyerhof pathway
      appeared to be a unique route.

PMID- 9579085
TI  - Use of resistant mutants to characterize the target of mycobacillin in
      Aspergillus niger membranes.
AB  - The mycobacillin-sensitive Aspergillus niger strain G3Br and resistant mutants of
      it did not show any differences in their total lipid content, although the
      amounts of phospholipids and sterols, particularly phosphatidylcholine and
      cholesterol, were lower in resistant cells. Mycobacillin resistance was
      accompanied by an increase in the phase-transition temperature of plasma membrane
      preparations. When exposed to mycobacillin, resistant and sensitive cells did not
      differ qualitatively with respect to most released materials (lysine, proline,
      Pi, Na+, K+, Ca2+); however, the release of ATP was completely inhibited in
      resistant cells unless they were exposed to concentrations of mycobacillin
      exceeding their respective MIC value. Resistant cells, under steady-state
      conditions, displayed greater uptake and release of the same specific materials-
      except ATP--as sensitive cells did under similar conditions. Thus release and
      uptake of those materials except ATP are not implicated in the mode of action of
      mycobacillin. The inhibiting action of mycobacillin (at concentrations higher
      than the MIC) on sensitive or resistant cells was completely antagonized by ATP
      (which did not form any complex with mycobacillin) but not by any of the
      releasable components, either alone or in combination. This observation, coupled
      with the authors' recent findings on ATP release, indicates that the fungistatic
      action of mycobacillin is due to excessive ATP release, leading to energy
      starvation. Interestingly, ATP release during the first 2 h of incubation with
      mycobacillin was minimal, but increased to over 96% during the next 48 h. Release
      and uptake of ATP via liposomes, prepared with lipid and protein isolated from
      membranes of the mycobacillin-sensitive parent and resistant mutants, showed that
      mycobacillin action could be inhibited either by resistant protein or by
      resistant lipid. The mycobacillin target appears to be a lipid-protein site on
      the membrane of sensitive A. niger G3Br.

PMID- 9579087
TI  - Simultaneous determination of urinary catecholamines and 5-hydroxyindoleamines by
      high-performance liquid chromatography with fluorescence detection.
AB  - A simple, selective and sensitive high-performance liquid chromatographic method
      with fluorescence detection is described for the simultaneous determination of
      catecholamines and 5-hydroxyindoleamines. The method is based on the
      derivatization of the amines with benzylamine in the presence of potassium
      hexacyanoferrate(III) under mild conditions. The resulting fluorescent
      derivatives are separated on a reversed-phase column, Cosmosil 5C18, using a
      mixture of acetonitrile and 10 mmol l-1 acetate buffer (pH 6.0) (35 + 65 v/v) as
      mobile phase, and are detected spectrofluorimetrically at 480 nm with excitation
      at 345 nm. The detection limits (signal-to-noise ratio = 3) for the amines are
      2.8-236.0 fmol for an injection volume of 50 microliters. The method was
      successfully applied to the determination of 5-hydroxyindol-3-ylacetic acid,
      serotonin, norepinephrine and epinephrine in human urine. The method is simple
      and does not require clean-up of urine samples.

PMID- 9579088
TI  - Determination of micellar self-diffusion coefficients by micellar electrokinetic
      chromatography.
AB  - A method is described by which the diffusion coefficients of electrically charged
      micelles can be determined using micellar electrokinetic chromatography (MEKC).
      The determination is based on a theory for the dispersion, at low electric field
      strengths, of analytes that are solubilized by only the micellar phase. The
      dispersion is represented by contributions from instrumental sources and from
      longitudinal diffusion. The latter depends on the micellar diffusion coefficient.
      The theory is used to determine the micellar diffusion coefficients of the
      surfactant sodium dodecyl sulfate in three solutions having different surfactant
      concentrations. These diffusion coefficients compare very favorably with those
      determined by diffusion-ordered two-dimensional NMR spectroscopy. An argument is
      presented justifying that the diffusion coefficients determined by MEKC are self
      diffusion coefficients.

PMID- 9579089
TI  - Optical fiber sensor for tetracycline antibiotics based on fluorescence quenching
      of covalently immobilized anthracene.
AB  - A new optical fiber sensor for tetracycline is fabricated with an anthracene
      containing copolymer prepared from 9-anthrylmethyl methacrylate, methyl
      methacrylate and n-butyl acrylate (PAMB). The sensing relies on the fact that the
      fluorescence of the sensor membrane fabricated with PAMB can be strongly quenched
      by the tetracycline antibiotics extracted from the sample. The proposed sensor
      responds linearly in the measuring ranges 2.02 x 10(-7)-2.02 x 10(-4) mol l-1
      tetracycline (TC), 2.00 x 10(-7)-2.03 x 10(-4) mol l-1 oxytetracycline (OTC) and
      4.05 x 10(-7)-2.03 x 10(-4) mol l-1 doxycycline (DC) and has detection limits of
      1.00 x 10(-7) mol l-1 for TC and OTC, and 2.00 x 10(-7) mol l-1 for DC. The
      leaching of anthracene from the sensor membrane was hindered by covalent
      immobilization, resulting in a drastically enhanced sensor lifetime. Moreover,
      the sensor can rapidly respond to the antibiotics of interest (ca. 30s) and
      exhibits good reproducibility, reversibility, and selectivity in the presence of
      some common pharmaceutical species as well as alkali and alkali-earth metal
      salts. The sensor was used for the direct assay of tetracycline antibiotics in
      commercial pharmaceutical preparations and urine. The results are comparable to
      those obtained by conventional spectrophotometry. The recovery for tetracycline
      antibiotics from urine samples is also satisfactory.

PMID- 9579090
TI  - Supported liquid membrane coupled on-line to potentiometric stripping analysis at
      a mercury-coated reticulated vitreous carbon electrode for trace metal
      determinations in urine.
AB  - A method for trace metal determinations in complex matrices is presented. The
      method combines supported liquid membrane (SLM) sample clean-up and enrichment
      with potentiometric stripping analysis (PSA) in a flow system using reticulated
      vitreous carbon (RVC) as the electrode material. The membrane contained 40% m/m
      di-2-ethylhexylphosphoric acid dissolved in kerosene. Lead was used as a model
      substance in high-purity water and urine samples. The samples were enriched after
      a simple pH adjustment. The SLM enrichment time was 10 min when the last 5 min
      electrodeposition on the RVC electrode at -1.0 V (versus Ag/AgCl) was performed
      simultaneously. The influence of various experimental parameters such as
      deposition time, deposition potential and flow rate on the lead signal was
      investigated. With a 10 min SLM enrichment including a 5 min deposition time, the
      detection limit for lead was 0.3 microgram l-1. The relative standard deviation
      for lead concentrations in the range 4-20 micrograms l-1 was 0.05%. The overall
      SLM-PSA system was found to be stable for at least 100 urine analyses. The method
      was validated by running a reference urine sample. The result obtained (five
      replicates) was 9.7 micrograms l-1 (standard deviation 1.8 micrograms l-1) which
      is within the recommended range of 9.2-10.8 micrograms l-1.

PMID- 9579091
TI  - [We need to know more about the process of medical education].

PMID- 9579092
TI  - [Imported fever. A diagnostic challenge].
AB  - Fevers without distinguishing symptoms in persons who have visited tropical or
      subtropical areas is an increasing health problem in most western countries. The
      condition may be caused by several different microbes, but among cases diagnosed
      in Norway five infections dominate: falciparum malaria, vivax malaria, typhoid
      fever, paratyphoid fever and dengue fever. Primary measures should be taken
      against immediate life-threatening diseases e.g. typhoid fever and falciparum
      malaria.

PMID- 9579093
TI  - [How to evaluate medical education? A Danish initiative in Scandinavia].

PMID- 9579094
TI  - [Swedish medical education evaluated, resulting in a positive picture].

PMID- 9579095
TI  - [Telemedicine goes to sea].

PMID- 9579096
TI  - [Introduction of teleradiology].
AB  - Against the background of Norwegian conditions, the authors outline the equipment
      needed to launch a teleradiology unit, and what the clinician using the unit
      might expect of such an imaging facility. They also discuss whether the unit
      should be organised with the needs of emergency care in mind or as an integrated
      part of everyday routine at the radiology department, how financing and judicial
      issues have been managed so far, and whether the introduction of teleradiology
      might effect relationships between health care personnel and patients.

PMID- 9579097
TI  - [More on the art of lecturing].

PMID- 9579098
TI  - [Positive effects of alcohol drinking?].

PMID- 9579099
TI  - [The effect of docetaxel on malignant tumors].
AB  - In recent years numerous molecular biological discoveries enlightened the various
      steps of the neoplastic transformation. Based on new targets, this development
      made it possible to synthetize new tumour inhibitory substances. Among them
      taxanes capable to block depolymerization of tubulin--which is an essential
      molecule in cell division--play an important role. Docetaxel (Taxotere) belongs
      to this group and is an active drug in the treatment of breast cancer. Moreover,
      platinum-resistant tumours may also respond to the therapy. It is important to
      note that even visceral (hepatic) metastases may express chemosensitivity.
      Results of combination chemotherapy seem to be also promising. The antitumour
      effect of Taxotere in NSCLC and other malignant neoplasms in under investigation.
      The toxicity of Taxotere may be successfully reduced by premedication of
      steroids. The necessary protective measures render the Taxotere therapy safe and
      of being perspectivistic.

PMID- 9579101
TI  - [Molecular biological studies on patients with nephrogenic diabetes insipidus].
AB  - Nephrogenic diabetes insipidus is a rare, mostly X-linked recessive disorder
      characterised by renal tubular resistance to the antidiuretic effect of arginine
      vasopressin. The gene responsible for the X-linked nephrogenic diabetes
      insipidus, the G-protein-coupled vasopressin V2-receptor, has been localised on
      the Xq28 region. In this study four patients were investigated with molecular
      genetic methods. Diagnosis was based on clinical symptoms and lack of increase of
      urinary osmolality after administration of the arginine vasopressin, or the
      synthetic vasopressin analogue DDAVP. Three different mutations (C112R, N317K,
      W323S) were found in three patients, while no mutation was detected in the fourth
      patient. Since earlier histiocytosis X has been diagnosed in this patient, this
      patient has probably central diabetes insipidus. Although the main symptoms of
      the disease can be found in all patients, there are significant differences in
      the seriousness of the symptoms as well as in some other symptoms. The
      explanations might be the different mutations in the V2-receptor gene and the
      various other genetic and environmental factors; these findings provide further
      evidence that X-linked nephrogen diabetes insipidus results from defects in the
      V2-receptor gene.

PMID- 9579100
TI  - [Histo-pathological evaluation of response to 6 and 12 months of interferon alpha
      therapy].
AB  - BACKGROUND AND AIMS: Interferon-alfa (IFN-alfa) has recently been introduced for
      chronic C hepatitis treatment; however, the response rate is merely 25-50%. The
      aims of this follow-up study were to compare the efficacy of 6 and 12-month IFN
      alfa treatment via liver biopsy scores and to evaluate the correlation with the
      biochemical response. PATIENTS AND METHODS: 20 chronic C hepatitis patients were
      studied. 10 patients received IFN-alfa therapy for 6 months, and 10 for 12 months
      (3 million units three times a week). Liver biopsy material was taken before and
      after therapy. RESULTS: There was a significant serum alanine aminotransferase
      (ALT) level improvement in both groups, but a significant histological
      improvement in necroinflammatory activity (grade) occurred only in the 12-month
      group. The Chevallier stage scores demonstrated a significant progression in both
      groups. CONCLUSIONS: 12-month IFN-alfa treatment affords a better response in the
      liver histology grade and serum ALT level, but not the stage; a normal ALT does
      not guarantee hepatitis inactivity. Liver biopsies appear indispensable for
      monitoring the fibrotic changes in chronic C hepatitis.

PMID- 9579102
TI  - [Diagnosis, prevention and therapy of osteoporosis].

PMID- 9579103
TI  - [An unusual case of morbid weight loss].
AB  - A 47 year old patient was admitted because of 20 kg weight loss and microcytic
      anaemia. There wasn't any important disease in his medical history. During
      examinations it has been found microcytic anaemia, hypoproteinaemia, low serum
      potassium, elevated prothrombin INR value, malabsorption and mild
      hepatosplenomegaly. After precluding the possibility of malignant disorders and
      any other chronic diseases, examinations have cleared Whipple-disease.

PMID- 9579104
TI  - Sound localization: information theory analysis.
AB  - Sound localization has been studied extensively. Curiously, although much is
      known about factors that affect errors, little is known about factors that
      influence response time. Three experiments were performed in an attempt to
      identify the separate influence of each of several different factors. All trials
      used a single broadband noise signal emanating from one of a subset of six
      loudspeakers equally spaced around the participant in the azimuthal plane. Both
      the size of the subset and the balance of relative probabilities from speaker to
      speaker were altered to evaluate the relationship between information content and
      the dependent variable, choice reaction time. Choice reaction time was found to
      be related to the information content of the sound stimulus in all cases. It was
      also found to be related to the presence of pairs of speakers that were
      symmetrically opposed in front of the behind the participant. Models of choice
      reaction time in a sound localization task have clear implications for practice.
      For example, they suggest that multiple auditory collision warnings may endanger
      drivers.

PMID- 9579105
TI  - Monitoring working memory load during computer-based tasks with EEG pattern
      recognition methods.
AB  - We assessed working memory load during computer use with neural network pattern
      recognition applied to EEG spectral features. Eight participants performed high-,
      moderate-, and low-load working memory tasks. Frontal theta EEG activity
      increased and alpha activity decreased with increasing load. These changes
      probably reflect task difficulty-related increases in mental effort and the
      proportion of cortical resources allocated to task performance. In network
      analyses, test data segments from high and low load levels were discriminated
      with better than 95% accuracy. More than 80% of test data segments associated
      with a moderate load could be discriminated from high- or low-load data segments.
      Statistically significant classification was also achieved when applying networks
      trained with data from one day to data from another day, when applying networks
      trained with data from one task to data from another task, and when applying
      networks trained with data from a group of participants to data from new
      participants. These results support the feasibility of using EEG-based methods
      for monitoring cognitive load during human-computer interaction.

PMID- 9579106
TI  - Effects of signal probability on individual differences in vigilance.
AB  - Decrements in the proportion of signals detected over time on task and large
      individual differences in performance are typical findings in studies of
      vigilance. This study investigates the effects of signal probability on
      individual differences in vigilance performance. Participants monitored stimulus
      events on computer displays over 2-h periods at three signal probability levels
      (.01, .04, & .12). Results were analyzed between groups, within groups, and
      within subjects. Detection decrements were found to be inversely related to
      signal probability levels across groups. High signal probabilities generated
      consistent within-group and within-subject performance, whereas low probabilities
      generated both lower performance and larger within-subject variance. This
      relationship between signal probability and within-group and within-subject
      variance has not been previously demonstrated. Future investigations should focus
      on the sources of both between-subjects and within-subject variation in vigilance
      performance in order to identify optimal interventions. Actual or potential
      applications include designing work to minimize vigilance decrement and maximize
      human performance under conditions that require sustained attention.

PMID- 9579107
TI  - Functional limitations to daily living tasks in the aged: a focus group analysis.
AB  - We assessed constraints on daily living of 59 healthy, active adults 65-88 years
      of age in focus group interviews. Individual comments about specific problems
      were coded along the dimensions of (a) the locus of the problem (motor, visual,
      auditory, cognitive, external, or health limitations); (b) the activity involved
      (e.g., transportation, leisure, housekeeping); (c) whether the problem was
      attributable to task difficulty or the perception of risk; and (d) response to
      limitations (perseverance, cessation, compensation, or self-improvement). The
      data provide information about the types of difficulties encountered in everyday
      activities as well as the way in which individuals respond to such difficulties.
      Each comment was also coded in terms of whether it was remediable via training,
      design changes, or some combination of the two. More than half of the problems
      that were reported had the potential to be improved in some way, thus providing
      direction for future research in human factors and aging. Actual or potential
      applications of this research include identifying problems and difficulties that
      older adults encounter in daily activities such as transportation and leisure;
      more specifically, determining the degree to which such problems are potentially
      remediable by human factors solutions. Applications of this research also include
      understanding the types of systems, products, and technologies that older adults
      interact with currently, or are interested in learning to use.

PMID- 9579108
TI  - Driver stress and performance on a driving simulator.
AB  - Effects of stress on driving performance can depend on the nature of driver's
      stress reactions and on the traffic environment. In an experimental study, we
      assessed multiple dimensions of vulnerability to driver stress by a questionnaire
      that was validated in previous field studies and related those dimensions to
      performance on a driving simulator. Results were broadly consistent with
      prediction. A dimension of habitual dislike of driving was associated with
      reduced control skills, greater caution, and disturbance of moods. A measure of
      aggressive driving predicted more frequent and more error-prone overtaking, which
      are effects attributed to the use of confrontive coping strategies in interaction
      with other vehicles. An alertness measure predicted speed of reaction to
      pedestrian hazards. This research has practical applications for system design,
      automated monitoring of driver performance, selection and assessment of drivers,
      and training.

PMID- 9579109
TI  - Work schedule and task factors in upper-extremity fatigue.
AB  - We tested the combined effects of work schedule and task factors on upper
      extremity fatigue in the laboratory during 8-h and 12-h shift schedules.
      Participants performed a simulated manual assembly task at three repetition rates
      and three torque loads and self-adjusted their work cycle duration to maintain
      fatigue at moderate levels. Work cycle durations decreased with increases in both
      load level and repetition rate. Fatigue was observed more quickly with increasing
      time on shifts and during night shifts compared with day shifts. Work schedule
      effects were most apparent at lighter workloads, with minimal differences at
      higher workloads. The highest fatigue levels were observed during 12-h night
      shifts, with similar levels reached by the end of both the week of 8-h night
      shifts and the week of 12-h day shifts. Overall durations were 20%-30% shorter
      than in previous short-term studies, which was likely a result of the more
      realistic work schedules used in this study. Results from this study could be
      applied to the design of work-rest schedules for manual tasks involving the upper
      extremities.

PMID- 9579110
TI  - Trunk muscle use during pulling tasks: effects of a lifting belt and footing
      conditions.
AB  - Pulling tasks require the torso to act as a rigid link in order to facilitate the
      force transmission between the ground and the hands. In this study, we tested the
      hypothesis that a lifting belt increases the rigidity of the torso, thereby
      increasing pulling strength or reducing trunk muscle forces, or both, as pulling
      tasks are performed. Twelve volunteers performed maximal and submaximal isometric
      pulling exertions; the latter were performed on nonslippery and slippery
      surfaces. Electromyographic data from 8 trunk muscles, trunk kinematic data, and
      ground reaction forces were sampled during each exertion. Results indicated that
      the lifting belt had no effect during maximal exertions on the maximal pull
      forces generated or the muscle recruitment levels, irrespective of the pulling
      posture. The lifting belt did not affect the EMG data obtained during the
      submaximal (40% of maximum) exertions, even when participants pulled on a
      slippery surface. However, the slippery surface increased the coactivation within
      the trunk musculature, perhaps stiffening the torso in the event of a slip. The
      absence of a statistical interaction effect between the lifting belt and the
      footing condition (slipperiness) indicates that the belt did not alter the
      coactivation pattern and hence was not relied upon by the participants as a
      protective mechanism. The data presented here will assist those who must make
      decisions regarding lifting-belt use and those who train individuals in manual
      materials handling techniques.

PMID- 9579111
TI  - Statins revisited.

PMID- 9579112
TI  - Antioxidant vitamins: no Egg McMuffin antidote.

PMID- 9579113
TI  - How passive is passive smoking?

PMID- 9579114
TI  - Don't panic: it's only panic disorder.

PMID- 9579115
TI  - Body weight and blood pressure.

PMID- 9579116
TI  - Olestra at the movies.

PMID- 9579117
TI  - I have been getting very short of breath with mild activities, like making my
      bed. My cardiologist says I have narrowing of my aortic valve that needs to be
      repaired with an operation. But I'm 87! Aren't I too old for a big operation?

PMID- 9579118
TI  - My total cholesterol level is in the "average" range, about 220 mg/dL. But my HDL
      cholesterol is above average, usually 55 mg/dL, and my LDL is 125 mg/dL. So what
      is my heart disease risk?

PMID- 9579119
TI  - 76th General session of the International Association for Dental Research. Nice,
      France, June 24-27, 1998. Abstracts.

PMID- 9579120
TI  - Planning for the future.

PMID- 9579122
TI  - Extended lymphadenectomy in gastric cancer: when, for whom and why.
AB  - Although lymph node metastasis is a major prognostic factor in gastric cancer,
      the optimal extent of lymph node dissection still remains a subject of debate.
      The influence of extended D2 lymphadenectomy on morbidity and long-term survival
      is controversial. Reports from many Japanese and some Western institutions show
      similar morbidity and mortality rates for both limited D1 and extended D2
      resections. However, the four available randomised trials show a significant
      increase in operative morbidity and mortality after a D2 resection. The authors
      of these trials believe that distal pancreaticosplenectomy is responsible for
      this increased morbidity and mortality and not the lymphadenectomy itself.
      Retrospective and prospective non-randomised studies show superior stage
      (II/IIIA) specific survival rates after D2 resections. However, these studies did
      not eliminate stage migration and randomised trials failed to show any survival
      advantage in favour of the D2 resection. Current data suggest that D2 resection
      is beneficial to the subgroup of patients with N1 or N2 disease undergoing
      potentially curative resection. However, Western studies that support D2
      resection, fail to show any survival advantage for D2 resection in N2 patients,
      reporting a benefit only to N0 or N1 patients. In contrast, Japanese series
      report a large number of N2 long-term survivors. The question as to the possible
      beneficial effect of extended lymphadenectomy in gastric cancer is difficult and
      complex. D2 resection increases the potentially curative resection rate, at least
      in N2 patients, achieves a better locoregional tumour control and provides the
      only chance for cure among N2 patients since adjuvant treatment in gastric
      carcinoma has not yet been proved effective. However, all randomised comparisons
      warn of an increased risk after D2 resection. By avoiding pancreaticosplenectomy,
      however, the morbidity can be within acceptable limits. D2 gastrectomy seems to
      be the most attractive procedure in the surgical management of gastric cancer.

PMID- 9579121
TI  - Vein quality in infrainguinal revascularisation: assessment by angioscopy and
      histology.
AB  - The concept of vein quality has been slow to gain widespread acceptance, but an
      increasing body of evidence suggests that vein quality is relevant to the success
      of bypass grafting for peripheral vascular disease. The angioscope represents an
      additional tool for monitoring and preparing vein grafts during infrainguinal
      revascularisation. Within the overall theme of vein quality, this paper presents
      the cumulative experience with vascular endoscopy at Bristol Royal Infirmary. In
      clinical studies, the diagnostic role of angioscopy in quality control was
      evaluated by grafting preexisting, angioscopically detected, intraluminal
      abnormalities and correlating them with histological appearances. There were
      significant associations between angioscopy/histology grades and graft patency.
      To enable quantification of images, an innovative computerised video image
      processing method has been developed and validated against simultaneous
      ultrasound measurements of segments of saphenous vein. The therapeutic
      applications of angioscopy in vein graft preparation were studied prospectively
      in patients undergoing in situ femoropopliteal/distal bypasses by randomisation
      to full angioscopic or conventional preparation. There was a significant
      reduction in wound morbidity. Completion angioscopy and arteriography were
      complementary in the detection of technical defects. Harvested vein was
      maintained in organ culture to assess further the influence of pre-existing
      pathology and the potentially traumatic effects of angioscopy on development of
      neointimal hyperplasia. There was a significant correlation between the extent of
      pre-existing abnormality and smooth muscle cell proliferative activity in culture
      and although angioscopy caused endothelial cell loss, this did not stimulate
      neointimal hyperplasia in vitro. This work confirms that vein quality can be
      evaluated prospectively by angioscopy and that substandard vein is associated
      with inferior patency rates. Angioscopic and histological evaluation, together
      with vein organ culture studies, have definite application in helping to
      elucidate the mechanisms underlying graft failure.

PMID- 9579123
TI  - Is cholecystectomy effective treatment for symptomatic gallstones? Clinical
      outcome after long-term follow-up.
AB  - The expectation that cholecystectomy is effective treatment for symptomatic
      gallstones is not always achieved in surgical practice. The impact of
      cholecystectomy on the relief of gastrointestinal symptoms was evaluated in 92
      patients followed up after surgery for a mean of 31.1 months (range 12-83
      months). Abdominal pain continued to be present, or arose de novo, in 28 (30.4%)
      patients. Pain-free outcome after cholecystectomy was associated with a
      preoperative clinical diagnosis of biliary colic, fatty food intolerance, and a
      thick-walled gallbladder on ultrasound (P = 0.02). Logistic regression associated
      a thick-walled gallbladder, elevated gamma-glutamyl transpetidase, body mass
      index < 26, fat intolerance, and normal bowel habit with good postoperative
      results (P = 0.001). Application of each of these five factors to a clinical
      index failed to predict long-term pain-free outcome after cholecystectomy.
      Abdominal bloating (P = 0.03), dyspepsia (P < 0.001), heartburn (P < 0.007), fat
      intolerance (P < 0.001), nausea (P = 0.001) and vomiting (P < 0.001) were
      significantly improved after cholecystectomy, but diarrhoea, constipation and
      excessive flatus were not. Outcome benefit ratios confirmed that vomiting (0.96),
      nausea (0.87), dyspepsia (0.67), fat intolerance (0.57) and heartburn (0.51) were
      relieved by surgery. Cholecystectomy improved symptoms compared with a matched
      control group, suggesting that surgery remains the gold standard treatment of
      symptomatic gallstones.

PMID- 9579124
TI  - Closure of transverse loop colostomy and loop ileostomy.
AB  - The aim of a defunctioning stoma is to protect patients from the consequences of
      faecal leakage and pelvic sepsis, should it occur. A retrospective audit of 77
      patients who had undergone closure of a loop stoma between 1988 and 1996 was
      performed. Sixty patients had either transverse loop colostomy (52) or loop
      ileostomy (8) to defunction distal colorectal/anal anastomoses or pathology, and
      17 patients had a loop ileostomy to defunction an ileoanal pouch. Those who had
      restorative proctocolectomy experienced a much higher (24%) complication rate
      than the loop colostomy group (5%), despite similar perioperative care and
      surgery performed by surgeons of equivalent seniority. The complication rate of
      ileostomy closure in pouch patients is similar to other published series. As a
      result of these findings, a selective approach to the use of loop ileostomy to
      protect pouches has been introduced. The absence of wound infections in our
      series would suggest that primary closure of the stomal wound without drainage
      can be achieved.

PMID- 9579125
TI  - 'Surgical' peritonitis in the CAPD patient.
AB  - Peritonitis is the most frequent cause for emergency hospital admission in
      continuous ambulatory peritoneal dialysis (CAPD) patients. Patients may present
      with 'surgical' peritonitis from other intra-abdominal pathology, but are treated
      initially as CAPD-related peritonitis. We present nine such cases, each failing
      to respond to standard conservative treatment, and ultimately coming to
      laparotomy. Of the nine patients, six survived, five transferring to long-term
      haemodialysis and one patient returning to CAPD. Failure to respond to standard
      measures should alert the physician to the possibility of an intra-abdominal
      emergency. The presence of enteric organisms, particularly E. coli, is an
      additional suspicious feature. The diagnosis may be difficult and we recommend
      early surgical referral and appropriate surgical measures (laparotomy rather than
      simple catheter removal) in order to decrease morbidity and mortality.

PMID- 9579126
TI  - A prospective audit of the usefulness of evacuating proctography.
AB  - Fifty-nine evacuating proctograms were performed over a 4 month period. We sought
      to identify how useful this technique is in diagnosing the cause of various
      anorectal symptoms and indicating which treatment option may be beneficial to the
      patient. The main reasons for referral were faecal soiling (60%) and obstructed
      defaecation (47%). Of the proctograms, 90% revealed some pathology. The most
      common abnormalities detected were rectocele (56%), rectal intussusception (39%),
      enterocele (19%) and rectal prolapse (12%). Of the patients, 45% were treated
      with an operation specific to the pathology detected on the proctogram; 29% did
      not require any active treatment and the remainder were managed with biofeedback
      conditioning or injection sclerotherapy. Evacuating proctography is of value in
      providing a diagnosis in patients with anorectal symptoms and thereby allowing
      specific treatment, operative or nonoperative, to be directed to the underlying
      pathology.

PMID- 9579127
TI  - Hirschsprung's disease: present UK practice.
AB  - A postal survey was performed to assess the management by consultant members of
      the British Association of Paediatric Surgeons (BAPS) of a well neonate with
      Hirschsprung's disease (HD). Replies were received from 63 (84%) of the 75
      consultant surgeons who operate on neonates with gastrointestinal problems.
      Twenty-six surgeons (41%) would aim to perform a primary pull through without
      colostomy, and 37 (51%) would stage the pull through, with stoma formation in the
      neonatal period. Timing of definitive surgery varied as did the choice of
      procedure (Soave 24%, Swenson 8%, Duhamel 62%, other 6%), but there was no
      evidence that surgical experience influenced the choice of operation. Most
      surgeons see 4-5 new cases of Hirschsprung's disease per year. This study shows
      great variation in operative procedures for the same clinical condition, and
      indicates the need for further audit.

PMID- 9579128
TI  - Investigation of suspected lower limb venous thrombosis.

PMID- 9579129
TI  - Protocol violation in deep vein thrombosis prophylaxis.
AB  - This study aimed to determine how closely deep vein thrombosis (DVT) prophylactic
      policies are adhered to in routine general surgical practice, to identify reasons
      for policy violations and to assess the effects of policy modification. Eight
      adult patients, sixty of whom had undergone an operation, under the care of six
      general surgeons, each with their own written DVT protocol, were studied on one
      weekday. Thirty patients (50%) did not receive DVT prophylaxis according to the
      policy of the relevant consultant. Most violations occurred for unacceptable
      reasons, mainly starting low-dose subcutaneous heparin or using thromboembolic
      stockings postoperatively. However, 43% of protocol violations occurred for
      acceptable clinical reasons. Following the initial study, a uniform departmental
      DVT prophylaxis policy was introduced. Nursing and medical staff were thoroughly
      appraised of the new policy. In a repeat study of 75 patients 1 year later, there
      were 15 protocol violations among 58 patients who had undergone an operation
      (27%). However, there were no violations for acceptable reasons. The number of
      unacceptable protocol violations in the two studies was similar (24/60 and
      17/56). The number of patients at moderate or high DVT risk who received no
      preoperative prophylaxis was the same in both studies (8/48 in both audits). DVT
      protocol violations are common in routine general surgical practice. Policy
      modification and unification results in fewer violations, but made little impact
      on the level of thromboprophylactic care.

PMID- 9579130
TI  - Influence of injection site for low-dose heparin on wound complication rates
      after inguinal hernia repair.
AB  - A high incidence of complications related to bleeding was observed after open
      prosthetic inguinal hernia repair. The site of injection of low-dose heparin into
      the abdominal wall was thought to be a possible causal factor for these
      complications. The wound complication rate after repair of primary unilateral
      inguinal hernias was recorded for 51 patients who had been given abdominal wall
      injections of heparin. Subsequently the injection site was changed to the upper
      limb in a further 63 patients and the incidence of wound complications recorded.
      A significantly higher incidence of haematomas and seromas was found in the
      abdominal wall injection group (39.2% vs 17.5%, P = 0.01). The role of low-dose
      heparin prophylaxis in inguinal hernia repair is discussed. We conclude that in
      those patients receiving heparin prophylaxis the injections should be given at a
      site remote from the operative area.

PMID- 9579131
TI  - Argon beam coagulation as an adjunct in breast-conserving surgery.
AB  - The development of a haematoma after wide excision of breast tumours is not
      uncommon. Suction drainage is commonly used to prevent this but often increases
      the hospital stay and can create unsightly wounds. Argon beam coagulation is a
      new technique which permits large 'raw' areas to be coagulated with minimal
      tissue damage. We believe that this technique may reduce the development of
      haematomas and seromas after breast surgery. We present our initial results using
      argon beam coagulation after wide excision of breast tumours in 80 patients
      without suction drainage. One patient required a single aspiration of a seroma at
      the site of breast lump excision and none required surgical drainage. Argon beam
      coagulation appears a useful adjunct in breast surgery and may help reduce
      hospital stay.

PMID- 9579132
TI  - A pump for use with tissue expansion in breast reconstruction.

PMID- 9579133
TI  - User-friendly simple device for fine needle aspiration biopsy.

PMID- 9579134
TI  - The balloonogram: a useful tool in vascular surgery.

PMID- 9579135
TI  - A simple alternative technique of orchiopexy for high undescended testis.
AB  - Medial displacement of the testicular vessels constitutes an important principle
      for a successful operation for high undescended testis. Prentiss's manoeuvre
      involving division of the fascia transversalis attempts to achieve this objective
      but has not found favour with surgeons because it is more invasive. A simple
      alternative procedure of rerouting the testicular pedicle behind the fascia
      transversalis is described. The technique has been reported earlier and this
      paper aims to illustrate the steps with the help of intraoperative photographs.
      This method serves as a fixation procedure owing to the 'button-hole' effect of a
      small pathway and may be combined with other techniques of scrotal fixation such
      as formation of a dartos pouch and suturing.

PMID- 9579136
TI  - Hazards of a 'healthy' diet.

PMID- 9579137
TI  - Pre- and postoperative chemotherapy for resectable gastric adenocarcinoma.

PMID- 9579138
TI  - Who decides the need for antibiotic prophylaxis in patients with major
      arthroplasties requiring dental treatment: is it a joint responsibility?

PMID- 9579139
TI  - Role of fine needle aspiration cytology in the management of the discrete parotid
      lump.

PMID- 9579140
TI  - Surgery for periampullary and pancreatic carcinoma: a Liverpool experience.

PMID- 9579141
TI  - Endoscopic palliation of malignant dysphagia.

PMID- 9579142
TI  - An audit of hospital mortality after urgent and emergency surgery in the elderly.

PMID- 9579143
TI  - Laparoscopic cholecystectomy without operative cholangiogram: 2038 cases over a 5
      year period in two district general hospitals.

PMID- 9579144
TI  - Chronic leg ulcers: beware the 'wolf in sheep's clothing!'.

PMID- 9579145
TI  - Chronic leg ulcers: beware the 'wolf in sheep's clothing!'.

PMID- 9579146
TI  - Chronic leg ulcers: beware the 'wolf in sheep's clothing!'.

PMID- 9579147
TI  - What's to be done about the malaise in science training in paediatrics and child
      health?

PMID- 9579148
TI  - Parents, parenting, and family breakdown.

PMID- 9579149
TI  - Developing injury surveillance in accident and emergency departments.

PMID- 9579150
TI  - Impact of improved glycaemic control on rates of hypoglycaemia in insulin
      dependent diabetes mellitus.
AB  - Increased emphasis on strict glycaemic control of insulin dependent diabetes
      mellitus (IDDM) in young patients may be expected to cause increases in rates of
      significant hypoglycaemia. To evaluate whether this is the case for a large
      population based sample of IDDM children and adolescents rates of severe (coma,
      convulsion) and moderate (requiring assistance for treatment) hypoglycaemia were
      studied prospectively over a four year period. A total of 709 patients were
      studied yielding 2027 patient years of data (mean (SD) age: 12.3 (4.4); range 0
      18 years, duration IDDM: 4.9 (3.8) years). Details of hypoglycaemia were recorded
      at clinic visits every three months when glycated haemoglobin (HbA1c) was also
      measured. Overall the incidence of severe hypoglycaemia was 7.8 and moderate was
      15.4 episodes/100 patient years. Over the four years mean (SD) clinic HbA1c
      steadily fell from 10.2 (1.6)% in 1992 to 8.8 (1.5)% in 1995. In parallel with
      this there was a dramatic increase in the rate of hypoglycaemia, especially in
      the fourth year of the study, when severe hypoglycaemia increased from 4.8 to
      15.6 episodes/100 patient years. This increase was particularly marked in younger
      children (< 6 years) in whom severe hypoglycaemia increased from 14.9 to 42.1
      episodes/100 patient years in 1995. It is concluded that attempts to achieve
      improved metabolic control must be accompanied by efforts to minimise the effects
      of significant hypoglycaemia, particularly in the younger age group.

PMID- 9579151
TI  - Randomised controlled trial of tyrosine supplementation on neuropsychological
      performance in phenylketonuria.
AB  - OBJECTIVE: To test the efficacy of tyrosine supplementation, as an adjunct to
      dietary treatment, on neuropsychological test performance in individuals with
      phenylketonuria. DESIGN: A randomised controlled trial of tyrosine
      supplementation using a double blind crossover procedure with three four week
      phases. SETTING: The Hospital for Sick Children, Toronto. PARTICIPANTS: 21
      individuals with phenylketonuria (ages 6 to 28 years, mean 11.3). INTERVENTION:
      Participants were given 100 mg/kg body weight/d of L-tyrosine or L-alanine
      (placebo). RESULTS: At baseline, performance on several of the neuropsychological
      test measures was correlated with tyrosine levels. Dietary supplements of
      tyrosine increased plasma tyrosine concentrations; however, no change in test
      performance was found across the tyrosine and placebo phases of the study.
      CONCLUSIONS: Tyrosine supplementation of this type does not appear to alter
      neuropsychological performance in individuals with phenylketonuria.

PMID- 9579152
TI  - Does a single plasma phenylalanine predict quality of control in phenylketonuria?
AB  - A 1993 MRC working group on phenylketonuria suggested standardising blood
      phenylalanine measurements by taking blood samples at the same time each day.
      Since it is not known how representative of a 24 hour period a single
      phenylalanine concentration is, the aim of this study was to investigate the 24
      hour variability of plasma phenylalanine in well controlled children with
      phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had
      hourly venous blood samples collected for 13 hours between 09.00 and 21.00 on one
      day. Serial skin puncture blood specimens were then collected at 24.00, 03.00,
      and 06.00 within the same 24 hour period. All food and drink was weighed. The
      median variation in plasma phenylalanine concentration was 155 mumol/l/day, with
      a minimum of 80 and a maximum of 280. The highest concentration occurred in the
      morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between
      midday and midnight in 94%. Concentrations < 100 mumol/l occurred in 46% of
      children below 11 years, three having concentrations < 30 mumol/l for two, six,
      and seven hours respectively. Three of five subjects had concentrations above the
      MRC guidelines for 24% of the period studied. Except in two subjects, the blood
      concentrations did not rise in response to phenylalanine consumption. However,
      the greater the quantity of protein substitute taken between waking and the 16.00
      specimen, the larger the decrease in daytime phenylalanine concentration (r = 
      0.7030) (p < 0.005). There is therefore wide variability in phenylalanine
      concentrations in a 24 hour period in children with phenylketonuria which is not
      reflected in a single observation. Further study is needed to investigate the
      effects of timing of protein substitute on the stability of phenylalanine
      concentrations.

PMID- 9579153
TI  - Clinical presentation and outcome in primary familial hypomagnesaemia.
AB  - The clinical presentation and long term outcome (mean follow up eight years,
      range 0.25 to 21) of 15 patients with autosomal recessive primary familial
      hypomagnesaemia is described. The most common (67%) presenting events were
      generalised hypocalcaemic-hypomagnesaemic seizures at a mean (SD) age of 4.9
      (2.5) weeks. Thirteen infants, treated soon after diagnosis with high dose
      enteral magnesium developed normally. Their serum calcium returned to normal
      concentrations but serum magnesium could not be maintained at normal
      concentrations (0.53 (0.12 SD) mmol/l; normal > 0.62). Delay in establishing a
      diagnosis led to a convulsive disorder with permanent neurological impairment in
      two infants. Reported complications of prolonged hypomagnesaemia such as renal
      stones, hypertension, arrhythmias, sudden death, or dyslipidaemia were not
      observed.

PMID- 9579154
TI  - Estimation of the energy cost of physical activity in infancy.
AB  - OBJECTIVE: To estimate physical activity energy expenditure (AEE) in groups of
      free living infants in the first year of life. DESIGN: Mixed longitudinal study
      of 124 healthy infants, using 232 estimations of AEE made between 1.5 and 12
      months. Infants studied at more than one time point were treated as new cross
      sectional data points. Total energy expenditure and body composition were
      estimated using doubly labelled water. Sleeping metabolic rate was predicted from
      weight. RESULTS: AEE increased from 5% of energy intake at 1.5 months to 34% at
      12 months. Growth costs declined by 90%, but metabolisable intake by only 20%,
      over the same period. CONCLUSIONS: Energy is increasingly diverted from growth to
      activity during infancy. Values for AEE may aid in estimating energy requirements
      of groups factorially. Further work is required, however, on individual
      variability in AEE, and on the effects of disease, hospitalisation, surgery, and
      malnutrition.

PMID- 9579155
TI  - Pulmonary function, exercise performance, and growth in survivors of congenital
      diaphragmatic hernia.
AB  - A cohort of survivors of congenital diaphragmatic hernia (CDH), with matched
      controls, was studied to assess growth, respiratory function, and exercise
      performance. Nineteen of 24 survivors from an 11 year period (79%) were compared
      with 19 matched controls. Subjects had detailed auxology, performed spirometry
      and cycle ergometry, and completed questionnaires about respiratory symptoms and
      exercise. There were no significant differences between the groups for height,
      weight, sitting height, head circumference, or body mass index expressed as SD
      scores. The mean (95% confidence interval) percentage predicted forced vital
      capacity (FVC) was 84.7% (79.1 to 90.3) in index cases and 96.5% (91.4 to 101.6)
      in controls (p < 0.01). There was no significant difference in total lung
      capacity. Expiratory flow rates corrected for FVC were also similar between
      groups, suggesting normal airway function relative to lung size. Mean maximum
      oxygen consumption in ml/kg/min was 40.1 (36.8 to 43.4) and 42.2 (38.5 to 45.8)
      in index and control cases. These differences were not significant. Index cases
      achieved a similar minute ventilation to controls by more rapid and shallower
      breathing. Index cases had lower perception of their own fitness and lower
      enjoyment of exercise, although habitual activity levels were similar. Survivors
      of CDH repair have reduced functional lung volumes, but normal airway function
      compared with matched controls. They have no growth impairment nor significant
      impairment of exercise performance, although they have more negative perceptions
      of their own fitness. They should be encouraged and expected to participate fully
      in sport and exercise.

PMID- 9579156
TI  - Preventable factors in hospital admissions for asthma.
AB  - Asthma remains the second most common cause for admissions to a paediatric
      hospital bed. The aim of this study was to describe the characteristics of
      children admitted to hospital with an acute asthma attack and to identify factors
      that may prevent future hospital admissions. Parents of all children aged 3 to 15
      years admitted to hospital for acute asthma were interviewed and the child's case
      record reviewed. Children were recruited consecutively in two groups: 141
      summer/autumn and 125 winter/spring 1996. According to the pattern of symptoms in
      the previous 12 months, 61% of the children had infrequent episodic asthma, 26%
      had frequent episodic asthma, and 13% persistent asthma. Only 8% of children aged
      8 years or less had persistent asthma, in contrast to 22% of those aged > 8
      years. There was evidence of both inadequate prescription of preventive treatment
      and poor compliance in the frequent episodic and persistent asthma groups. Of the
      whole group, 44% had previously been given an acute asthma management plan, but
      only 9% of them used it before the current hospital admission. There was a delay
      in seeking medical advice (> 24 hours after the onset of symptoms) in 27% of all
      admissions. This study has identified potential areas where intervention may
      reduce the number of future admissions.

PMID- 9579157
TI  - Oestrogen treatment of constitutional tall stature: a risk-benefit ratio.
AB  - Oestrogens are given in high doses for the treatment of tall stature in girls.
      The aim of this study was to obtain data considering efficiency, side effects,
      and acceptance of the treatment of 50 constitutionally tall girls treated with
      conjugated oestrogens (7.5-11.25 mg/day). The mean (SD) adult height predictions
      were 188.3 (4.4) cm and the achieved height was 5.2 (3.3) cm less than the
      predicted height. A greater reduction from final predicted height occurred when
      treatment was started at an early bone age (< 13.0 years) and with a remaining
      growth potential of greater than 10 cm. Even postmenarcheal girls, however, had a
      mean reduction of 4.8 (3.2) cm. The main side effects were considerable weight
      gain (> 10 kg), an increase in triglyceride concentrations (37.5% of the
      patients), and increased platelet aggregation (60% of the patients). Altogether
      84.6% of the patients were satisfied with the treatment and 15.4% regretted
      having had it.

PMID- 9579158
TI  - Precocious puberty in girls adopted from developing countries.
AB  - Nineteen girls adopted from developing countries were referred for signs of
      idiopathic precocious puberty. After adoption, the catch up in linear and weight
      growth, together with improved nutritional and psychological conditions, may
      trigger the onset of puberty. Precocious puberty is a frequent and unnatural
      event in these girls. Treatment with gonadotrophin releasing analogues is
      indicated in patients diagnosed early, and when height prediction is poor.

PMID- 9579159
TI  - Gastric tonometry in septic shock.
AB  - OBJECTIVES: To investigate the prognostic value of intramucosal pH (pHi) and the
      relation among pHi, arterial pH, base excess, and lactate in children with septic
      shock. DESIGN: Children admitted to the paediatric intensive care unit with a
      diagnosis of septic shock were prospectively enrolled. A gastrointestinal
      tonometer (Tonometrics Division, Instrumentarium Corporation, Helsinki, Finland)
      was placed into the stomach and intramucosal pH, arterial pH, base deficit, and
      lactate were measured on admission and six hours later. Sequential data were
      analysed on 24 patients (17 survivors, seven non-survivors), median age 46 months
      (range: 2.8-168 months). RESULTS: Median pHi on admission was 7.39 (interquartile
      range 7.36-7.51) in survivors compared with 7.2 (interquartile range 7.18-7.35)
      in non-survivors (p = 0.01). There was no significant difference in arterial pH,
      base excess, or lactate among survivors and non-survivors. Admission pHi < 7.32
      predicted mortality with sensitivity (57%), specificity (94%), and positive
      predictive value (80%). Patients with admission pHi < 7.32 who failed to improve
      > or = 7.32 within six hours (n = 3) had 100% mortality. CONCLUSION: In children
      with septic shock the admission pHi is significantly lower in non-survivors. pHi
      is a better prognostic indicator of mortality than either standard acid-base
      values or lactate. pHi < 7.32 that does not improve within six hours is
      associated with a poor prognosis.

PMID- 9579160
TI  - Tuberous sclerosis complex and Wolff-Parkinson-White syndrome.
AB  - This report highlights the association between tuberous sclerosis and Wolff
      Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff
      Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson
      White syndrome presented early in life, nine cases being diagnosed in the first
      year. Eight of the 10 cases were male. In eight cases, the syndrome was
      associated with supraventricular tachycardias, and in nine with cardiac
      rhabdomyomata. One child died from cardiac failure secondary to obstruction of
      the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors
      showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory
      pathway was localised in nine patients from surface electrocardiograms: six
      children had left sided pathways and three had right sided pathways.

PMID- 9579161
TI  - Cardiac sequelae of Kawasaki disease among recurrent cases.
AB  - OBJECTIVE: This study was undertaken to clarify whether cardiac sequelae due to
      Kawasaki disease are more frequent among recurrent cases than initial onset
      cases. STUDY DESIGN: A cross sectional study using data from nationwide surveys
      of Kawasaki disease in Japan was conducted. A total of 33,976 patients reported
      were divided into two groups: initial onset cases (32,923 patients) and recurrent
      cases (1053 patients). Proportions of cardiac sequelae such as coronary
      aneurysms/dilatation, coronary stenosis/narrowing, myocardial infarction, and
      valvular lesions were compared between the two groups. RESULTS: The proportions
      of patients with the sequelae were significantly more common among recurrent
      cases. In men 25.5% of the recurrent cases had the sequelae in comparison with
      14.9% for initial onset cases, and in women 16.1% of recurrent cases had the
      sequelae compared with 9.8% of initial onset cases. Giant coronary aneurysms were
      twice as likely in men in whom the disease was recurring than in initial onset
      cases, and 1.5 times more likely in women in whom the disease was recurring than
      in initial onset cases. CONCLUSION: Cardiac sequelae of Kawasaki disease are more
      likely to appear on recurrent case patients.

PMID- 9579162
TI  - Reducing bacterial contamination of enteral feeds.
AB  - OBJECTIVE: It has previously been shown that microbial contamination of enteral
      feeds given to children in hospital and at home is common. This study therefore
      examined the effects of improvements in the enteral feeding protocol, coupled
      with an intensive staff training programme, on bacterial contamination. METHODS:
      The enteral feeding protocol was modified by: priming the feeding set on an
      alcohol treated metal tray, spraying the bottle opener and top with 70% alcohol,
      wearing non-sterile disposable gloves, and filling the feeding reservoir with
      feed for up to 24 hours' use rather than only four hours. Daily feeds samples
      were collected from 16 inpatients and home patients on enteral nutrition at the
      start and end of feeding. Seventy seven samples were cultured. Results were
      compared with previously published control data. RESULTS: Enteral feed
      contamination rates were reduced significantly from 62% to 6% of feeds given at
      home (p < 0.001), and from 45% to 4% of feeds given in hospital (p < 0.001).
      CONCLUSIONS: This study highlights the importance of using an appropriate enteral
      feeding protocol, and of regular staff training in reducing contamination rates
      of enteral feeds to an acceptable level.

PMID- 9579163
TI  - Rifampicin and isoniazid prophylactic chemotherapy for tuberculosis.
AB  - Prophylaxis of tuberculosis in children with four month (n = 53) and three month
      regimens (n = 213) of rifampicin and isoniazid from 1987 to 1996 were tolerated
      without any toxicity. The reduction in the proportion of paediatric tuberculosis,
      which was seen after the introduction of chemoprophylaxis with longer regimens in
      1981, was maintained with the shorter duration regimens. Altered immigration
      patterns and a fall in the proportion of infectious tuberculosis, as defined by
      sputum culture positivity, have been excluded as factors in the reduced
      paediatric proportion of tuberculosis. The data show such regimens have little
      toxicity and provide indirect evidence that three months chemoprophylaxis may be
      as effective as longer regimens.

PMID- 9579164
TI  - Duration of growth suppressive effects of regular inhaled corticosteroids.
AB  - The growth of 50 children receiving regular inhaled corticosteroids was
      segregated into divisions of six weeks from the start of treatment and compared
      with their growth when not receiving regular corticosteroids using a random
      effects regression model. Growth suppression was most marked during the initial
      six weeks after starting treatment, with most suppression occurring during the
      initial 18 weeks. Thereafter the children's growth was similar to their growth
      when not receiving treatment. These findings have important consequences for
      patterns of treatment of asthma in children.

PMID- 9579165
TI  - Current means of obtaining a MD degree in the UK.
AB  - To investigate the current means of obtaining a MD a questionnaire was sent to 55
      doctors who had obtained a MD in a paediatric subject between 1984 and 1993; 53
      (93%) responses were obtained. Ten (18%) of the respondents had done their MD
      during a clinical post. The remainder had research posts lasting 10-87 months
      (median 24). Only 29% of those in research posts were able to submit their MD by
      the end of their post. The time from starting [corrected] the MD to confirmation
      that it had been obtained was 21-102 months (median 54). Of those in research
      posts 0-80% (median 20) of their time was spent on non-research related
      activities and 45% had regular on call commitments. It took 2-15 months (median
      6) before candidates received their MD back from their examiners. Altogether 46%
      of candidates had to make revisions to their MD and 47% of candidates had a viva.
      There is great variation in the current means of obtaining a MD and it is
      suggested that nationwide regulations are adopted for the conduct of MD degrees.

PMID- 9579166
TI  - DNA repair disorders.

PMID- 9579167
TI  - Disorders of cholesterol biosynthesis.

PMID- 9579168
TI  - Advances in haemolytic uraemic syndrome.

PMID- 9579169
TI  - Intestinal lymphangiectasia and protein losing enteropathy responding to small
      bowel restriction.

PMID- 9579170
TI  - Cystic fibrosis in Down's syndrome--diagnostic pitfalls and implications for the
      clinician.

PMID- 9579171
TI  - Nutritional impact of antipseudomonas intravenous antibiotic courses in cystic
      fibrosis.

PMID- 9579172
TI  - Asthma--time for a change of name?

PMID- 9579173
TI  - Adolescent health services.

PMID- 9579174
TI  - How to organise the paediatric MRCP (UK). Part II. Clinical examination.

PMID- 9579175
TI  - Venous thromboembolic disease.
AB  - The advent of spiral CT has encouraged investigation into the diagnosis of venous
      thromboembolic disease. It has also exposed the limitations of prior methods of
      investigation and raised questions as to the significance of small pulmonary
      emboli. This article discusses this new technique, the clinical detection of
      venous thromboembolic disease and possible current and future strategies in
      diagnosis.

PMID- 9579176
TI  - Maximum intensity projection images in the detection of simulated pulmonary
      nodules by spiral CT.
AB  - This study was undertaken to investigate the use of maximum intensity projection
      (MIP) images in the detection of pulmonary nodules by spiral CT (SCT). 40
      pulmonary nodules of high density were created by endobronchial deployment of 2
      and 4 mm beads in the peripheral airways of five anesthetized dogs. Standard SCT
      was performed with 5 mm collimation, pitch 2 and reconstruction of contiguous
      slices. MIP images were generated from overlapped slabs of seven consecutive 3 mm
      slices, reconstructed at 2 mm intervals and acquired at pitch 2. Scans were
      reviewed by six radiologists. The data were modelled using ordinal logistic
      regression for repeated measures, and the Wald chi 2 statistic used to test if
      there was a difference in nodule detection and reader confidence level between
      the two techniques. MIP imaging increased the odds of nodule detection by 2.18 (p
      = 0.0002). Reader confidence level for nodule detection was significantly higher
      with MIP images (p < 0.00001). MIP images improve the detection rate for small
      high density pulmonary nodules and increase reader confidence level, when
      compared with standard SCT.

PMID- 9579177
TI  - Magnetic resonance imaging of fistula-in-ano: STIR or SPIR?
AB  - Patients with clinically suspected anorectal sepsis were studied using MRI in
      order to determine if T2 weighted sequences with fat suppression conveyed any
      additional benefit over conventional short tau inversion recovery (STIR)
      sequences. 23 consecutive patients (16 male) undergoing MRI for suspected
      perianal sepsis were studied prospectively using a 1.0 T whole body system and
      body coil. Axial and coronal T1 weighted turbo spin echo sequences were obtained,
      followed by STIR and T2 weighted spectral fat saturation inversion recovery
      (SPIR) sequences. Images were assessed for the presence of sepsis or fistula, and
      information provided by the sequences compared. Active disease was diagnosed in
      17 patients, 14 of whom had fistula-in-ano; one intersphincteric, 10
      transsphincteric and three extrasphincteric. Internal openings were identified in
      all of these 14 patients; anal in 10, rectal in two, and both in two. Diagnosis
      and fistula classification was possible in all of these 14 subjects on the basis
      of STIR sequences alone. The anal sphincters and pelvic floor musculature were
      better resolved by STIR than SPIR, leading to easier and more confident
      determination of fistula anatomy in eight of the 14 (57%). In no case did STIR
      sequences fail to resolve inflammation seen subsequently on SPIR, despite reduced
      track intensity. T1 weighted sequences were generally non-contributory. Both STIR
      and SPIR sequences are adequate to classify fistula-in-ano, but classification
      was easier with STIR due to superior resolution of pelvic floor structures.

PMID- 9579178
TI  - Spontaneous rupture of renal tumours: the role of imaging in diagnosis and
      management.
AB  - This study aimed to evaluate whether patients presenting with spontaneous
      haemorrhage from renal tumours could be accurately diagnosed and initially
      managed conservatively, and evaluate the role of imaging in guiding the timing
      and type of subsequent operation. The clinical features, imaging findings and
      management of seven patients presenting with spontaneous rupture of renal tumour
      over a 5-year period were reviewed. The information from various imaging studies
      was evaluated in relation to the subsequent course of intervention. The tumours
      consisted of six angiomyolipomas and one renal cell carcinoma. In all cases,
      imaging studies were diagnostic, with computed tomography being the most useful
      single modality. Emergency surgery was required in one patient for evacuation of
      suspected infected haematoma and wedge excision of angiomyolipoma. Three elective
      nephrectomies were performed, while three other patients with ruptured
      angiomyolipoma were treated conservatively and remained well, without any
      intervention. In conclusion, patients presenting with spontaneous rupture of
      renal tumour can be managed conservatively initially. Imaging facilitates
      accurate pre-operative diagnosis, which was angiomyolipoma in all but one patient
      in this series. The subsequent intervention can be tailored according to the
      lesion type and the anticipated risk of re-haemorrhage.

PMID- 9579179
TI  - Cervical assessment by magnetic resonance imaging--its relationship to
      gestational age and interval to delivery.
AB  - The aim of this cross-sectional study was to assess the uterine cervix in late
      pregnancy, using MRI, and to study its relationship to the gestational age and
      the time interval to delivery. 91 women with a singleton cephalic presenting
      fetus had MRI of the pelvis between 35 and 41 weeks. All had had one prior lower
      segment Caesarean section and no history of prior vaginal delivery. The cervical
      length, internal and external os diameter, cervical signal intensity and the
      angulation of the cervix with the cephalocaudal axis were measured on sagittal T2
      weighted images and correlated with the gestational age and the interval from the
      MRI examination to delivery. It was found that the signal intensity of the
      cervical stroma increased with the gestational age. A higher signal intensity in
      the cervical stroma was associated with a shorter time interval to delivery.
      Deliveries after 40 weeks tended to occur more commonly in those with lower
      signal intensity in the cervical stroma and also in those with a smaller external
      os diameter. It is concluded that cervical softening as assessed on MRI
      correlated with gestational age and the time interval to delivery.

PMID- 9579180
TI  - Experiences with functional magnetic resonance imaging at 1 tesla.
AB  - Functional magnetic resonance imaging (fMRI) has been performed on a standard 1 T
      system using a pulse sequence developed to utilize blood oxygen level dependent
      (BOLD) contrast and an off-line analysis routine using correlation techniques.
      The sequence and the data analysis routine have been validated by reproducing the
      conventional hand movement paradigm studies reported by numerous other workers.
      Our work has then been extended to investigate cerebral foci for a tonic pain
      stimulus and the cortical representation of oesophageal stimulation. Both these
      studies relate to paradigms where the expected BOLD signal is significantly less
      than that encountered for motor or visual cortex paradigms. The results show good
      agreement with other modalities (positron emission tomography,
      magnetoencephalography and cortical evoked potentials). Performing fMRI at 1 T is
      slightly controversial. However, our successful study of demanding paradigms,
      using a standard clinical 1 T imaging system, has important implications for many
      other users operating at this field strength.

PMID- 9579181
TI  - Distance learning in mammographic digital image processing.
AB  - The potential of interactive multimedia and Internet technologies is investigated
      with respect to the implementation of a distance learning system in medical
      imaging. The system is built according to a client-server architecture, based on
      the Internet infrastructure, composed of server nodes conceptually modelled as
      World Wide Web (WWW) sites. Sites are implemented by integration and
      customization of available components. The system evolves around network
      delivered interactive multimedia courses and network-based tutoring, which
      constitute its main learning features. This potential has been demonstrated by
      means of an implemented system, validated with digital image processing content,
      specifically image enhancement. Image enhancement methods are theoretically
      described and applied on mammograms. Emphasis is given in the interactive
      presentation of the effects of algorithm parameters on images. The system end
      user access depends on available bandwidth, so high speed access can be achieved
      via LAN or local ISDN connections.

PMID- 9579182
TI  - A study of patient radiation doses in interventional radiological procedures.
AB  - Patient radiation doses received during interventional radiological procedures
      can be significant. To aid in the establishment of reference dose levels, a
      patient dose survey has been conducted of such procedures. A total of 288 non
      coronary procedures (177 classified as diagnostic and 111 as therapeutic) were
      accrued into the study. For each procedure, the fluoroscopy screening time and
      the fluoroscopic and digital radiographic dose-area products were recorded in a
      computer database. For example, median dose-area product values (due to
      fluoroscopy and digital radiography combined) of 24.2, 27.9, 69.6 and 74.7 Gy cm2
      were obtained for nephrostomy, biliary stent removal/insertion, cerebral
      angiography and percutaneous transhepatic cholangiography procedures. While the
      effective dose is not an accurate measure of patient risk, it is convenient for
      comparing the radiological risks associated with various procedures. Effective
      doses were estimated from the total dose-area products. The respective median
      estimated effective dose values for the four procedures noted above were 3.9,
      4.5, 7.0 and 12.0 mSv. While an infrequently performed procedure at this
      institution (n = 4 during this survey), the transjugular intrahepatic
      portosystemic shunt (TIPS) procedure had the greatest median dose-area product
      and effective dose values: 347 Gy cm2 and 55.5 mSv, respectively. Excluding the
      extreme case of TIPS, it was found that among commonly-performed procedures,
      those that are categorized as therapeutic do not necessarily present a
      statistically significant greater radiation risk than those which are diagnostic.
      Comparisons between dose-area product values obtained from this study are made
      with data from other interventional radiology patient dose surveys and reasons
      for some differences noted are discussed.

PMID- 9579183
TI  - Digital radiography in paediatrics: radiation dose considerations and magnitude
      of possible dose reduction.
AB  - The purpose of this study was to evaluate the radiation doses received by
      paediatric patients examined using a digital radiography unit, and to compare
      these doses with those received from conventional screen-film systems. In this
      way, guidelines could be drawn up concerning the magnitude of possible dose
      reductions achievable using digital radiography. The study was undertaken on
      approximately 900 patients undergoing abdomen, chest, pelvis and skull
      examinations. Patients were categorized into the following age groups: 0-1 month,
      1-12 months, 1-5 years, 5-10 years and 10-15 years. Approximately half were X
      rayed using a Fuji computed radiography system and half using a conventional
      screen-film system. Entrance surface dose was calculated from the recorded
      exposure parameters and measured X-ray tube outputs. Dose-area product was
      recorded directly. Image quality was assessed clinically using criteria
      recommended by a working group of the Commission of the European Communities.
      Apart from chest examinations, it was found possible to reduce doses by about 40%
      on average, by using a computed radiography system instead of a 600 speed screen
      film combination. There was no significant difference in the dose for chest
      examinations. Satisfactory image quality can therefore be achieved by using
      computed radiography as a 1000 speed system for abdomen, pelvis and skull
      examinations, and as a 600 speed system for chests. Since very few departments
      appear to use screen-film systems of speeds greater than 400, then, for most
      departments, the use of computed radiography would result in dose reductions of
      at least 60%, or 33% for chests.

PMID- 9579184
TI  - The practical peak voltage of diagnostic X-ray generators.
AB  - A new quantity termed the "practical peak voltage" is proposed. This quantity is
      derived by equating the low level contrast in an exposure made with an X-ray tube
      connected to a generator delivering any arbitrary wave form, to the contrast
      produced by the same X-ray tube connected to a constant potential generator. Out
      of the great number of possible contrast configurations one is selected as being
      suitable for diagnostic radiology. By means of an eigenvalue problem a direct
      link is established between the electrical quantity X-ray tube voltage and the
      practical peak voltage which was initially defined through the properties of the
      X-ray field. It is shown that the spread in total X-ray tube filtration as
      encountered in medical diagnostic radiology can influence the result of a
      measurement of the practical peak voltage only marginally.

PMID- 9579185
TI  - The average dose-area product at intravenous urography in 205 adults.
AB  - The intravenous urography (IVU) is the most important and most frequently
      performed radiological examination in urology. This prospective study determined
      the dose-area product as a measurement of radiation dose in 205 adult patients
      undergoing IVU. Average dose-area product was 1017 cGy cm2. An average 3.7
      radiographs were obtained per patient. Tomographic views were required in only
      8.8% of cases. Radiation dose is dependent not only on the number and size of the
      obtained radiographs, but on the physical constitution of the patient. The dose
      area products measured show a clear relationship to the body weight of the
      patient.

PMID- 9579186
TI  - Supradiaphragmatic middle aorta syndrome--MR and angiographic imaging.
AB  - We describe the case of an asymptomatic 24-year-old man with hypertension who was
      investigated for aortic coarctation but found on MR scanning to have narrowing of
      the distal thoracic aorta. Stenosis of the thoracolumbar aorta--the Middle Aorta
      Syndrome--is rare and is usually found below the diaphragm. The MRI and
      angiographic findings are presented.

PMID- 9579187
TI  - Bronchial atresia associated with epibronchial right pulmonary artery and
      aberrant right middle lobe artery.
AB  - We report a case of bronchial atresia associated with an epibronchial right
      pulmonary artery (ERPA) and an aberrant right middle lobe artery (ARMLA). CT
      showed a branching opacity, which was hyperintense on MR images, in the anterior
      segment of the right upper lobe with segmental hyperinflation and the ERPA. At
      surgery, the ARMLA was found to originate from the ERPA, crossing the anterior
      aspect of the right upper lobe bronchus. It is postulated that the ARMLA might
      have interfered with the normal bronchial development, leading to the development
      of segmental bronchial atresia.

PMID- 9579188
TI  - Leiomyosarcoma of the maxillary sinus: CT and MRI findings.
AB  - This report describes the CT and MRI appearances of a leiomyosarcoma of the
      maxillary sinus. CT showed frank bony destruction, no calcification and a low
      attenuation area within the mass. MRI showed intermediate intensity on T1
      weighted images, intermediate to slightly high signal intensity on T2 weighted
      images and moderate inhomogeneous enhancement. Precise identification of the
      extent of the tumour, especially of orbital invasion, is of utmost importance
      because local recurrence is common after the resection of leiomyosarcomas.

PMID- 9579189
TI  - Familial osteoma of the cranial vault.
AB  - A case of solitary osteoma of the parietal skull is described in a mother and her
      12-year-old son. There were no other craniofacial or dysmorphic features and
      there was no history of previous cranial trauma or inflammatory process and no
      radiographic evidence of other skeletal lesions in both patients. Family history
      was otherwise unremarkable. Gardner syndrome was ruled out by excluding other
      associated clinical abnormalities and by family history. The clinical and
      radiological features of the patients' osteomas were different from those of
      Albright hereditary osteodystrophy, fibrodysplasia ossificans progressiva,
      progressive osseous heteroplasia and familial ectopic ossification. To the
      author's knowledge this is the first case of the familial presentation of
      osteomas.

PMID- 9579190
TI  - Pancreatic cancer as a second tumour following treatment of Hodgkin's disease.
AB  - Over the past 30 years, the life expectancy in patients with Hodgkin's disease
      has greatly improved. However, adverse long-term side-effects are now well
      recognized and development of second malignancies is one of the most important.
      We report the case of a patient who developed pancreatic cancer 9 years after
      treatment, with chemotherapy and radiation, for Hodgkin's disease. The increasing
      number and variety of solid tumours after curative treatment of Hodgkin's disease
      points to a need for new, less toxic regimens.

PMID- 9579191
TI  - Cranial trauma following birth in term infants.
AB  - The purpose of this pictorial review is to demonstrate the imaging features of a
      range of cranial injuries associated with birth at term. Scalp and skull injuries
      include simple cephalhaematoma, osteomyelitis of the skull vault from infected
      cephalhaematoma, subgaleal haemorrhage and skull fracture. Intracranial injuries
      include extradural, subdural and subarachnoid haemorrhage, leptomeningeal cyst
      and brain infarct. Radiologists need to be aware of the range of cranial injuries
      following birth and their differentiating features.

PMID- 9579192
TI  - An unusual metastatic involvement.

PMID- 9579193
TI  - Rebound vasoconstriction of the small pulmonary arteries following short exposure
      to radiographic contrast media.

PMID- 9579194
TI  - Transcolostomy hydrostatic reduction of intussusception.

PMID- 9579196
TI  - Clarification: a billing service can bill for a percentage of monies.

PMID- 9579195
TI  - Rontgen's other experiment--a further development.

PMID- 9579197
TI  - Capitation concept lacks understanding.

PMID- 9579198
TI  - Reader suggests Poe died from mercury poisoning.

PMID- 9579199
TI  - The death of Edgar Allan Poe--a case of syphilis?

PMID- 9579200
TI  - Ethical group capitation.

PMID- 9579201
TI  - Preventing wading pool suction-drain injuries.
AB  - Wading pools with displaced drain covers and single drain outlets can lead to
      life-threatening injuries. This is a case of a Maryland child who sustained
      transanal suction which resulted in prolapse and avulsion of the small intestine
      from its blood supply. Because the injury would likely have been prevented if at
      least one of three safety precautions had been followed, standards for pool
      operation and pool design are reviewed.

PMID- 9579202
TI  - Dengue fever: a risk to travelers.
AB  - An outbreak of dengue fever occurred among a small group of Maryland and
      Pennsylvania residents following a trip to the British Virgin Islands in January
      1996. Dengue fever is a mosquito-borne viral illness that occurs primarily in
      tropical urban areas. Most dengue infections are benign and self-limited, but
      some produce severe and fatal hemorrhagic disease. Although dengue is not endemic
      in the continental United States, travelers may acquire the infection during
      visits to the tropics. Physicians should consider dengue in the differential
      diagnosis of a patient with a febrile illness and a history of recent travel to a
      tropical area. Travelers to endemic areas should be advised to take precautions
      to prevent mosquito bites.

PMID- 9579203
TI  - Osteoporosis: a focus on treatment.

PMID- 9579204
TI  - A rational approach to psychological testing of adults with mental retardation.
AB  - Intelligence (IQ) tests and scales of adaptive behavior are typically used to
      evaluate adults with mental retardation. Personality tests and instruments
      designed to measure behavior problems and psychopathology are also used. Repeated
      IQ testing is common but not useful for adults. Adaptive behavior scales and
      measures of psychopathology do appear useful, although the latter are relatively
      new and not widely used in clinical practice. Tests requiring skilled language
      responses are not useful for people with severe and profound disabilities. The
      problem of administering the tests is addressed by interviewing people who are
      knowledgeable about the person being evaluated; this method is limited by the
      actual knowledge of the person interviewed. Neuroimaging, still in the research
      stage, may be especially relevant in the future.

PMID- 9579205
TI  - Looking back to May 1909: opening of the new faculty building-1211 Cathedral
      street.

PMID- 9579206
TI  - 1997 spring meeting of the World's Poultry Science Association (UK branch).
      Scarborough, United Kingdom, 26-27 March 1997. Abstracts.

PMID- 9579207
TI  - ICD-10 Guide for Headaches. International Headache Classification Committee.

PMID- 9579208
TI  - Cumulative index (author, subject, volume contents) for volumes 1-50.

PMID- 9579209
TI  - Treatment of cutaneous leishmaniasis with antimony: intramuscular versus
      intralesional administration.
AB  - The various methods used to treat cutaneous leishmaniasis (CL) have not given
      consistent results. The aim of the present study was to compare the efficacy of a
      solution of meglumine antimoniate (MA; 85 mg Sb/ml) given intralesionally (i.l.)
      with that of the same solution given intramuscularly (i.m.). Eighty CL patients,
      with a total of 147 lesions, were randomly allocated into the two treatment
      groups. Forty were injected i.m. with MA (15 mg Sb/kg.day) on 6 days/week until
      12 injections had been given to each. The lesions of the other 40 patients were
      infiltrated with MA (0.2-0.8 ml/lesion) every other day for 30 days. After 15
      days' therapy, none of the lesions on those treated i.m. had fully healed
      (although five lesions showed some improvement) whereas two lesions on those
      treated i.l. had fully healed and 10 showed good improvement. After 30 days, 46
      (68%) of the 68 lesions on those treated i.m. had healed completely, 11 (16%) had
      improved, and five (8%) worsened. The corresponding values for the 66 lesions on
      those treated i.l. were 48 (73%), 10 (15%) and three (5%). There was no
      statistically significant difference between the two treatment groups, either in
      terms of satisfactory response (lesions fully healed or improved) or
      unsatisfactory response (lesions unchanged or advanced), when assessed on day 30
      (P > 0.5). Intralesional antimony is a rapidly effective, safe and economical
      method of treating simple CL, particularly in patients with cardiac, liver or
      renal disease, for whom antimonials are contra-indicated.

PMID- 9579210
TI  - Integration of schistosomiasis-control activities into the primary-health-care
      system in the Gizan region, Saudi Arabia.
AB  - A few decades ago, the prevalence of Schistosoma haematobium infection in the
      human inhabitants of the Gizan region of Saudi Arabia was very high (43%-91%). A
      vertical programme for the control of the disease, by case finding, treatment of
      infected individuals and by chemical snail control, was begun in 1974 and led to
      significant reductions in prevalence in most areas. In 1989 the control
      activities were gradually integrated into the primary-health-care (PHC) system.
      Several schools in the area recently participated in the detection of ova (among
      schoolchildren and neighbouring communities) and organized health-education
      sessions. The records taken during the vertical and PHC programmes indicate that
      there were more diagnoses and higher chemotherapy coverage in the latter. The PHC
      programme has maintained the overall prevalence of infection at an extremely low
      level (< 1%) and the infection has been completely eradicated in several areas.
      The participation of schools proved to be particularly useful in terms of
      population coverage and health education.

PMID- 9579211
TI  - Monitoring the abundance of Aedes (Ochlerotatus) albifasciatus (Macquart 1838)
      (Diptera: Culicidae) to the south of Mar Chiquita Lake, central Argentina, with
      the aid of remote sensing.
AB  - Surges in the size of adult populations of the flood-water mosquito Aedes
      albifasciatus can produce important economical losses because of the way this
      species irritates livestock. Although this species is also the main vector of
      west equine encephalitis in Argentina, little is known about the factors
      affecting its population dynamics, as it is difficult to obtain data on its
      abundance over a large area. However, the results of intensive study of the
      mosquito in a few sites might reasonably be extrapolated to a regional scale by
      the use of remotely sensed data. The adult, larval and pupal stages of Ae.
      albifasciatus were sampled at five field sites to the south of Mar Chiquita Lake,
      either once a month (during the dry, cold season) or once a fortnight (during the
      warm, rainy season), between August 1992 and April 1993. The measured abundance
      of adults or pre-adults and a meteorological coefficient useful for the
      estimation of larval abundance each showed significant correlation with various
      statistics derived from normalized-difference, vegetation indices (NDVI)
      calculated from satellite (NOAA-AVHRR) imagery. A linear discriminant analysis,
      using data on NDVI, rainfall and temperature, accurately identified periods with
      and without pre-adults. The satellite imagery was also useful in the estimation
      of larval abundance and consequently could be used to predict adult abundance 7
      days in advance. Even though the satellite data employed have poor spatial
      resolution, their high temporal resolution makes them very useful in studies of
      the population dynamics of mosquitoes in general, at least once the relevant
      variables and their relationships with mosquito breeding and survival have been
      identified.

PMID- 9579212
TI  - Host preferences of Triatoma sordida.
AB  - Triatoma sordida is a widespread vector of Trypanosoma cruzi, living in both
      sylvatic and domestic habitats. To see if Tri. sordida 'prefers' to feed from
      avian or mammalian hosts, two experiments were carried out. In the first
      experiment, in which fifth-instar nymphs were allowed free access to two
      unrestrained hosts, a guinea-pig and a pigeon, 98% of those feeding fed on the
      guinea-pig, and the mammalian bloodmeals were generally larger than the avian,
      with mean weights of 50.9 and 30.2 mg, respectively. In the second experiment,
      groups of nymphs were exposed to a single host (guinea-pig or pigeon) at two
      different densities (10 and 30 bugs/host). Whatever the density of the bugs, a
      much larger proportion of the bugs offered feeds on the guinea-pig took
      bloodmeals than of those offered the pigeon (55% v. 9%), and the bugs which fed
      on the mammal again generally took larger bloodmeals (mean weight = 50.9 mg) than
      the few which fed on the bird (mean weight = 12.8 mg; P < 0.0001). Bug density
      was found to have a greater effect on the size of the bloodmeals taken from
      pigeon than on those taken from guinea-pig. Triatoma sordida therefore does not
      appear to have a marked preference for avian blood; it is probably a generalist
      species that can invade a variety of habitats to exploit the range of available
      vertebrate hosts.

PMID- 9579213
TI  - Laboratory assessment of the molluscicidal and cercaricidal activities of the
      Egyptian weed, Solanum nigrum L.
AB  - The molluscicidal properties of Solanum nigrum L. were tested against three
      Egyptian snail species (Biomphalaria alexandrina, Bulinus truncatus and Lymnaea
      natalensis), each an intermediate host of parasites causing human schistosomiasis
      or fascioliasis. The plant was collected in two regions within Egypt: Fayium and
      Giza. Snails were exposed for 24 and 48 h, to the dry powdered fruits and leaves
      or to crude water extracts of the powders, and mortality was recorded. The water
      extract of the leaves collected in Fayium (FLWE) had the highest molluscicidal
      activity, with median lethal concentrations (LC50) of 18.6 mg/litre for Bi.
      alexandrina, 14.5 mg/litre for Bu. truncatus and 17.7 mg/litre for L. natalensis.
      When Bi. alexandrina infected with Schistosoma mansoni were exposed to FLWE (20
      or 25 mg/litre), they shed significantly fewer cercariae than unexposed snails (P
      < 0.02). The cercaricidal properties of FLWE were directly tested against S.
      haematobium, S. mansoni and Fasciola gigantica cercariae and a time-concentration
      relationship was observed; the concentrations needed to kill all cercariae
      (LC100) within 30 min of exposure were 30 mg/litre for both S. haematobium and S.
      mansoni and 40 mg/litre for F. gigantica.

PMID- 9579214
TI  - Primaquine-tolerant vivax malaria in Thailand.

PMID- 9579215
TI  - Correlation between rainfall and malaria in the dry zone of Sri Lanka.

PMID- 9579216
TI  - Confirmation of two distinct classes of zymodemes of Trypanosoma brucei infecting
      man and wild mammals in Cote d'Ivoire: suspected difference in pathogenicity.

PMID- 9579217
TI  - A high prevalence of cystic hydatid disease in North Africa.

PMID- 9579218
TI  - Molecular diagnosis of human dirofilariasis.

PMID- 9579219
TI  - Detection of hybrids in natural populations of the Anopheles gambiae complex by
      the rDNA-based, PCR method.

PMID- 9579220
TI  - Traditional treatments for snake bite in a rural African community.

PMID- 9579221
TI  - Human ACTH hypersensitivity syndrome associated with abnormalities of the ACTH
      receptor gene.
AB  - OBJECTIVE: Activating mutations of the ACTH receptor have not been previously
      described. We investigated a 69-year-old woman with normal blood cortisol but
      undetectable blood ACTH concentrations. The aim of this study was to evaluate her
      hypothalamo-pituitary-adrenal axis by measuring circadian variation in blood ACTH
      and cortisol, and by performing CRH and ACTH stimulation and dexamethasone
      suppression tests. We also examined biological activity of her circulating blood
      ACTH using bovine adrenocortical cell suspensions and ACTH receptor gene
      structure by Northern blotting analysis. RESULTS: Random plasma cortisol
      concentrations ranged from 182 to 328 nmol/l, while ACTH concentrations were
      always undetectable. After an intravenous bolus injection of human CRH 100
      micrograms, plasma ACTH rose slightly, while plasma cortisol increased
      appropriately. ACTH stimulation tests revealed that a small amount of ACTH (5
      ng/kg b.w.) had the maximal cortisol stimulatory activity, and even smaller
      amounts of ACTH (0.5 and 0.05 ng/kg b.w.) produced significant increases in
      cortisol levels. ACTH bioassay of the patient's plasma demonstrated weak
      biological activity in the HPLC fractions which corresponded to the band of
      synthetic human ACTH 1-39. The ACTH receptor coding region was amplified by
      polymerase chain reaction using the leucocyte genomic DNA. There were two base
      mutations; cysteine 21-->arginine and serine 247-->glycine in the sequences
      coding for the first extramembranous N-terminal domain and the third
      extramembranous loop of the ACTH receptor. CONCLUSIONS: This patient with normal
      blood cortisol but undetectable ACTH levels showed increased adrenocortical
      sensitivity to ACTH and two point mutations in the ACTH receptor gene. This
      study, therefore, reports a previously undescribed syndrome--ACTH
      hypersensitivity syndrome--and provides insights into the molecular mechanism of
      ACTH receptor action.

PMID- 9579222
TI  - Receptor hypersensitivity: a new phenomenon?

PMID- 9579223
TI  - Left ventricular function in young adults with childhood and adulthood onset
      growth hormone deficiency.
AB  - OBJECTIVE: The impairment of heart structure and function in adults with
      childhood onset GH deficiency has been recently described. However, previous
      echocardiographic studies have reported no differences in cardiac mass and
      function between adulthood onset GH deficient patients and healthy subjects.
      DESIGN: The aim of this study was to evaluate cardiac performance in adult
      patients with childhood and adulthood onset GH deficiency, using equilibrium
      radionuclide angiography, a method more accurate than echocardiography. PATIENTS:
      Eleven patients with childhood onset GH deficiency, 9 patients with adulthood
      onset GH deficiency and 12 age-, gender-, height- and weight-matched healthy
      subjects entered the study. MEASUREMENTS: All the study population underwent
      equilibrium radionuclide angiography at rest and during physical exercise.
      RESULTS: Both childhood and adulthood onset GH deficient patients had an impaired
      left ventricular systolic performance both at rest (ejection fraction was 55 +/-
      6%, 55 +/- 10% and 66 +/- 6% in childhood and adulthood onset GH deficient
      patients and control group, respectively; P < 0.0001) and during physical
      exercise (ejection fraction was 54 +/- 9% in childhood onset GH deficient
      patients, 53 +/- 9% in adulthood onset GH deficient patients and 76 +/- 7% in
      normal subjects; P < 0.0001). Peak ejection rate was 3.2 +/- 0.8 end-diastolic
      volume/second, 3.0 +/- 0.6 end-diastolic volume/second and 3.9 +/- 0.8 end
      diastolic volume/ second in childhood and adulthood onset GH deficient patients
      and control group, respectively (P < 0.01). Exercise-induced changes in end
      systolic volume were increased in both groups of patients compared with healthy
      subjects. In contrast, exercise-induced end-diastolic volume changes were not
      different between GH deficient patients and controls. Resting peak filling rate
      was 2.6 +/- 0.7 end-diastolic volume/second, 2.5 +/- 0.7 end-diastolic volume/
      second and 3.1 +/- 0.3 end-diastolic volume/second in the 2 groups of patients
      and healthy subjects, respectively (P < 0.05). Reduced exercise tolerance in all
      patients, as shown by the significantly lower values of peak workload (P <
      0.0001), peak rate-pressure product (P < 0.01) and exercise duration (P < 0.0001)
      was observed. CONCLUSION: Patients affected by GH deficiency have left
      ventricular systolic dysfunction at rest and during physical exercise, suggesting
      that GH plays a physiological role in maintaining normal cardiac performance in
      humans. Furthermore, no difference between childhood and adulthood onset GH
      deficient patients was found indicating that both group of patients have an
      impairment of cardiac function.

PMID- 9579224
TI  - Circulating levels of adrenomedullin in patients with Addison's disease before
      and after corticosteroid treatment.
AB  - BACKGROUND AND OBJECTIVE: A novel hypotensive peptide, adrenomedullin (AM), had
      recently been isolated, purifed and its encoding gene sequenced from a human
      phaeochromocytoma. In humans AM circulates in physiological levels and possesses
      a distinct vasodilatatory activity. The purpose of this study was to examine the
      behaviour of AM levels in primary adrenal failure. DESIGN: Plasma AM levels were
      measured in patients with proven Addison's disease using a specific
      radioimmunoassay and compared to those in healthy normotensive subjects.
      PATIENTS: Eighteen patients with Addison's disease (10 men and eight women; ages
      21 to 72 years) and 21 healthy control subjects (13 men and eight women; ages 20
      to 71 years) were enrolled in the study. All patients were studied under basal
      conditions and 10 were reassessed following corticosteroid treatment. RESULTS:
      All patients with Addison's disease showed increased levels of AM compared to the
      control group. Mean plasma AM levels were correspondingly higher in patients with
      Addison's disease than in normal subjects (102.1 +/- 33.4 (SD) ng/l versus 13.7
      +/- 6.1 ng/l; P < 0.0001). In 10 patients studied after corticosteroid treatment,
      plasma AM levels were significantly reduced (P < 0.0001: 110.3 +/- 35.8 ng/l
      versus 32.4 +/- 10.3 ng/l) after 2 weeks of treatment. A weak correlation (r =
      0.458; P = 0.048) was observed between systolic blood pressure and plasma AM
      concentrations in all patients with Addison's disease. CONCLUSIONS: These results
      indicate a consistent but reversible increase of adrenomedullin in patients with
      Addison's disease.

PMID- 9579225
TI  - Prevalence of hypertension in acromegalic patients: clinical measurement versus
      24-hour ambulatory blood pressure monitoring.
AB  - OBJECTIVE: Hypertension is thought to play an important role in the pathogenesis
      of acromegalic cardiomyopathy. So far, hypertension has been defined by clinical
      measurement, with considerable variations reported concerning its prevalence in
      acromegalics. DESIGN: To determine the mean blood pressure (BP) values and the
      prevalence of hypertension in patients with active acromegaly according to non
      invasive 24-hour ambulatory BP monitoring (ABPM) and to compare the data obtained
      with those provided by clinical measurement. PATIENTS: Forty patients with active
      acromegaly (22 women, 18 men, mean age 48.6 +/- 12.5 years) were included.
      Patients were in wash-out for antihypertensive treatment and none had been using
      any medical treatment for acromegaly for at least 3 months before the study. All
      were studied as outpatients. MEASUREMENTS: Clinical BP values were calculated as
      the mean of BP values obtained by standard sphygmomanometric measurement in three
      separate occasions. Mean 24-hour, daytime and night-time BP values were obtained
      by ABPM. RESULTS: The mean 24-hour BP values were lower than clinical BP values,
      the difference being significant for both systolic BP (SBP: 131.1 +/- 21.5 versus
      136.1 +/- 16.3 mmHg, P < 0.02) and for diastolic BP (DBP: 74.6 +/- 10.6 versus
      88.8 +/- 9.1 mmHg, P < 0.0001). ABPM values recorded during the daytime were
      137.8 +/- 20.9 mmHg for SBP and 78.6 +/- 11.5 mmHg for DBP, the latter being
      significantly lower than the corresponding clinical BP values (P < 0.0001). About
      60% of the patients considered hypertensive by clinical measurement were found to
      be normotensive by ABPM, thereby decreasing the prevalence of hypertension in
      this series from 42.5% to 17.5% according to ABPM (P < 0.02). In contrast, all
      patients defined as normotensive by clinical measurement were also normotensive
      by ABPM. CONCLUSIONS: Ambulatory blood-pressure monitoring indicated a lower
      prevalence of hypertension in acromegalic patients then usually reported,
      suggesting that the role of hypertension in the pathogenesis of acromegalic
      cardiomyopathy is commonly overestimated. We propose that ambulatory blood
      pressure monitoring should be routinely proposed in acromegalics with high or
      borderline clinical blood pressure values although it is not useful in patients
      defined normotensive according to repeated clinical measurement.

PMID- 9579226
TI  - The effect of growth hormone replacement therapy on cortisol-cortisone
      interconversion in hypopituitary adults: evidence for growth hormone modulation
      of extrarenal 11 beta-hydroxysteroid dehydrogenase activity.
AB  - OBJECTIVE: Growth hormone (GH) replacement therapy in hypopituitary adults has
      been associated with a decreased urinary ratio of 11-hydroxy/11-oxo-cortisol
      metabolites (CoM). This could result from GH regulation of the activity of
      hepatic or renal 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1 and 2), the
      enzymes responsible for cortisol-cortisone interconversion, or alternatively it
      might reflect decreased cortisol availability. To elucidate this, we examined the
      effect of GH on urinary cortisol, cortisone and cortisol metabolites in
      hypopituitary adults at increasing doses of hydrocortisone replacement. DESIGN:
      Patients received increasing twice daily doses of hydrocortisone (HC) (10/10,
      20/10, 40/20 mg) each week, before and during 2 months of GH replacement (0.25
      U/kg/week). PATIENTS: Seven hypopituitary adults (three men and four women, age
      range 47-64 years) with combined GH and ACTH deficiency. Three additional
      patients with GH deficiency, but intact ACTH reserve, were also studied.
      MEASUREMENTS: Urine steroid metabolite profiles were measured in 24-hour urine
      collections by gas chromatography after each week of treatment. Urinary free
      cortisol and free cortisone were measured by radioimmunoassay as a measure of
      renal 11 beta-HSD-2 activity. RESULTS: Total urinary CoM increased with rising
      doses of HC, but at each particular HC dose, were unchanged after GH (before
      versus after GH, median (range): 9.67 (7.86-12.59) versus 9.93 (8.31-14.08);
      15.87 (12.37-31.39) versus 17.07 (12.64-23.81); 26.68 (19.07-42.14) versus 26.77
      (8.01-37.62) mg/24 hours). The urine ratio 11-hydroxy/11-oxo-CoM decreased
      significantly with GH treatment, at each HC dose schedule (1.22 (1.02-1.96)
      versus 0.92 (0.83-1.63) P = 0.018; 1.53 (1.30-2.23) versus 1.23 (0.93-1.46) P =
      0.018; 1.87 (1.45-2.70) versus 1.56 (1.22-1.79) P = 0.018). The urinary ratio
      tetrahydrocortisols/tetrahydrocortisone, an alternative index of 11 beta-HSD
      activity, also fell with GH therapy at each HC dose (P = 0.049; P = 0.018; P =
      0.043). In contrast, the urinary 20-hydroxy/20-oxo-CoM ratio exhibited a small
      increase with GH, suggesting that the changes observed above were not simply due
      to changes in redox status. The patients with GH deficiency, but intact ACTH
      reserve, demonstrated changes in urine steroid profiles similar to the group
      receiving hydrocortisone replacement. Urinary free cortisone and urinary free
      cortisol/free cortisone ratios did not change with GH therapy, but the serum
      cortisol/ cortisone ratio fell significantly with GH therapy at each
      hydrocortisone dose. CONCLUSIONS: GH therapy decreases the urinary ratios 11
      hydroxy/11-oxo-cortisol metabolites and tetrahydrocortisols/tetrahydrocortisone,
      but not urinary free cortisone or the urinary free cortisol/free cortisone ratio.
      This effect is not secondary to reduced cortisol availability. These findings
      provide further evidence for direct or indirect modulation of cortisol metabolism
      by growth hormone and suggest that this occurs at hepatic or an alternative site
      of 11 beta-hydroxysteroid dehydrogenase-1 activity.

PMID- 9579227
TI  - Intestinal calcium absorption in men with spinal osteoporosis.
AB  - OBJECTIVE: To investigate the role of serum 1,25-dihydroxyvitamin D (1,25D) in
      the decreased calcium absorption found in men with osteoporosis. DESIGN:
      Prospective study of patients referred to a university teaching hospital clinic
      for investigation of possible osteoporosis. PATIENTS: Male patients referred for
      investigation for osteoporosis, from 1981 to 1995, because of specific risk
      factors or radiological suspicion of osteoporosis. Men with vertebral compression
      fractures were compared with those without. MEASUREMENTS: Height and weight,
      radiocalcium absorption, serum 1,25D and fasting urinary calcium and
      hydroxyproline excretion. RESULTS: The men with vertebral fractures had higher
      fasting urinary hydroxyproline excretion (P = 0.003) and lower calcium absorption
      (P = 0.002) than the men without. Calcium absorption was positively related to
      1,25D in both groups but the estimated calcium absorption at zero 1,25D was lower
      in the osteoporotic than the normal group. 1,25D was lower in the osteoporotic
      group than in the normal group. However this difference could only explain about
      half of the difference in calcium absorption between the groups. CONCLUSIONS:
      Calcium absorption is low in men with osteoporosis. About half of the deficit is
      due to low serum 1,25-dihydroxy vitamin D levels but there appears, in addition,
      to be some intestinal resistance to its effect on calcium absorption.

PMID- 9579228
TI  - Effect of hyperandrogenism and menstrual cycle abnormalities on bone mass and
      bone turnover in young women.
AB  - OBJECTIVE: Prolonged period of amenorrhoea are regarded as a risk factor for the
      appearance of osteoporosis. Amenorrhoea is a feature of different pathological
      conditions with heterogeneous endocrine profiles. We evaluated bone mineral
      metabolism in patients with polycystic ovary syndrome (PCOS), hypothalamic
      amenorrhoea and idiopathic hirsutism in order to establish the relative
      importance for the maintenance of normal bone mass of ovulatory cycles and
      androgen and oestrogen production. PATIENTS AND MEASUREMENTS: Bone mineral
      density (BMD), bone turnover markers and endocrine profile were evaluated in 51
      patients with PCOS, 24 patients with idiopathic hirsutism, 26 patients with
      hypothalamic amenorrhoea and 35 healthy women. Body mass index (BMI) ranged
      between 20.1 and 31.0 kg/m2, and age from 17 to 33 years. Thirty-eight of the
      PCOS patients were amenorrhoeic (< 4 menstrual cycles/year). RESULTS: Spine and
      femoral BMD were significantly decreased and bone markers (serum osteocalcin, and
      urinary excretion of free deoxypyridinoline, cross-linked N-telopeptide and
      hydroxyproline) significantly increased in the patients with hypothalamic
      amenorrhoea, when compared to control subjects and the other two patient groups.
      In the sub-group of PCOS patients with amenorrhoea, spine and femoral neck BMD
      was significantly lower than in patients with idiopathic hirsutism and the non
      amenorrhoeic PCOS patients. In all PCOS patients, spine and neck BMD were
      positively correlated (P < 0.05) with serum androstenedione and free testosterone
      levels. CONCLUSIONS: The results of this study suggest that in patients with
      polycystic ovary syndrome the deleterious effect on bone of amenorrhoea is
      balanced by androgen overproduction.

PMID- 9579229
TI  - The altered plasma amino acid pattern is responsible for the paradoxical growth
      hormone response to the oral glucose tolerance test in liver cirrhosis.
AB  - OBJECTIVE: An increased basal growth hormone (GH) secretion and a parodoxical GH
      response to the oral glucose tolerance test (OGTT) have been reported in patients
      with liver cirrhosis. It has been suggested that the ratio between branched-chain
      amino acids (BCAAs) and aromatic amino acids (AAAs) (BCAA/ AAA ratio) may
      determine in part the brain concentration of the AAAs, since the BCAAs compete
      with the AAAs for entry across the blood-brain barrier, leading to the
      accumulation of false neurotransmitters such as octopamine and
      phenylethanolamine, which are able to stimulate GH secretion (via alpha 2
      adrenergic stimulation). In this study we investigated the role of amino acids,
      particularly the BCAA/AAA ratio, in the paradoxical response of GH to the OGTT in
      patients with liver cirrhosis. PATIENTS AND DESIGN: Twelve non-diabetic patients
      with biopsy-proven cirrhosis of the liver underwent an OGTT. Three of the five
      patients with a paradoxical response of GH to the OGTT underwent a second oral
      glucose administration associated with an infusion of BCAA solution from -30 min
      until 180 min. RESULTS: During the OGTT, glucose and insulin levels increased
      from 4.8 +/- 0.2 to 9.6 +/- 0.7 mmol/l (P < 0.001) and from 18.8 +/- 2.6 to 104.4
      +/- 13.8 mU/l (P < 0.005), respectively. GH levels increased from 8.6 +/- 2.6 to
      22.4 +/- 10.8 mU/l although not significantly. Five patients had a paradoxical GH
      response to the OGTT. A negative correlation between serum GH values and BCAA/AAA
      ratio in the plasma at every time point of the OGTT was found. After co
      administration of glucose and BCAA in three patients the BCAA/AAAs ratio
      increased, abolishing the paradoxical GH secretion. CONCLUSIONS: Our data suggest
      that in liver cirrhosis the altered BCAA/AAA ratio may influence the altered
      basal GH secretion and the paradoxical GH response to the OGTT, probably by an
      increase of adrenergic mediators in the brain. Moreover, the increase of BCAA/AAA
      ratio seems to be able to abolish the GH paradoxical response to the OGTT.

PMID- 9579230
TI  - Increased leptin production in vivo and insulin cleavage by the omental adipose
      tissue of morbidly obese patients.
AB  - OBJECTIVE: The aim of this investigation was to assess the insulin cleavage
      capacity in obese humans. Increased insulin degradation by visceral adipose
      tissue has previously been demonstrated in obese rats and could be interpreted as
      a physiological response to hyperinsulinaemia. The recent characterization of
      leptin receptors in pancreatic beta cells, liver and muscle suggests that leptin
      may influence insulin function and metabolism. Our study focuses on the possible
      relationship between leptin secretion and adipose tissue insulin-degrading
      capacity. DESIGN AND PATIENTS: Insulin and leptin were measured in arterial blood
      and in the epiploic vein of morbidly obese (n = 7) and non-obese patients (n = 7)
      who were undergoing abdominal surgery. Arteriovenous insulin difference (AV
      insulin) was considered an in vivo marker of insulin degradation by the omental
      fat tissue. Statistical comparison between venous and arterial leptin was used to
      assess endogenous leptin production. MEASUREMENTS: Insulin was measured using an
      oligoclonal IRMA and leptin levels were determined by using a specific
      radioimmunoassay. RESULTS: Morbidly obese patients were hyperinsulinaemic
      compared to non-obese patients according to arterial insulin levels (P = 0.049)
      but not to venous levels. Insulin cleavage capacity, nil in the control group,
      was clearly significant in the morbidly obese patients (P = 0.001). In the
      morbidly obese group, leptin levels in venous epiploic samples were significantly
      higher (P = 0.028) than in the arterial samples, confirming in situ the synthesis
      of leptin by human white adipose tissue. We also observed a correlation between
      insulin arterial levels and venous leptin concentrations (P = 0.009) which
      supports the chronic leptinogenic effect of insulin suggested in previous works.
      Finally, our results show that venous leptin levels are correlated with the
      extent of insulin cleavage by omental tissue (P = 0.033). CONCLUSIONS: Morbidly
      obese patients have a higher white adipose tissue insulin cleavage capacity,
      which could partially diminish hyperinsulinaemia-derived adverse effects. High
      leptin production, a consequence of high insulin levels, may act as a signal to
      the insulin-degrading tissues in order to lower insulinaemia.

PMID- 9579231
TI  - Effects of testosterone replacement on HDL subfractions and apolipoprotein A-I
      containing lipoproteins.
AB  - OBJECTIVES: Gonadal steroids are important regulators of lipoprotein metabolism.
      The aims of this study were to determine the effects of a minimum effective dose
      of testosterone replacement on high density lipoprotein (HDL) subfractions and
      apolipoprotein (apo) A-I containing particles (lipoprotein (Lp)A-I) and LpA-I:A
      II) in hypogonadal men with primary testicular failure and to investigate the
      underlying mechanisms of these changes. MEASUREMENTS: Eleven Chinese hypogonadal
      men were started on testosterone enanthate 250 mg intramuscularly at 4-weekly
      intervals. HDL was subfractionated by density gradient ultracentrifugation and
      LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 weeks of
      treatment. Plasma cholesteryl ester transfer protein (CETP) activity and
      lipolytic enzymes activities in post-heparin plasma were measured to determine
      the mechanisms underlying testosterone-induced changes in HDL. RESULTS: The
      dosage of testosterone enanthate used in the present study resulted in suboptimal
      trough testosterone levels. No changes were seen in plasma total cholesterol,
      triglyceride, low density lipoprotein cholesterol (LDL-C,) apo B and apo(a) after
      12 weeks. There was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l
      vs. 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in
      HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Plasma apo A-I
      decreased after treatment (1.34 +/- 0.25 g/l vs. 1.50 +/- 0.29, P < 0.01), due to
      a reduction in LpA-I:A-II particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P <
      0.01). No changes were observed in the levels of LpA-I particles. No significant
      changes were seen in plasma CETP and lipoprotein lipase activities after
      testosterone replacement but there was a transient increase in hepatic lipase
      (HL) activity at weeks 3 and 6. The decrease in HDL correlated with the increase
      in HL activity (r = 0.62, P < 0.05). CONCLUSIONS: Testosterone replacement in the
      form of parenteral testosterone ester given 4-weekly, although unphysiological,
      was not associated with unfavourable changes in lipid profiles. The reduction in
      HDL was mainly in HDL3-C and in LpA-I:A-II particles and not in the more anti
      atherogenic HDL2 and LpA-I particles. The changes in HDL subclasses were mainly
      mediated through the effect of testosterone on hepatic lipase activity.

PMID- 9579232
TI  - Differences between sporadic and multiple endocrine neoplasia type 2A
      phaeochromocytoma.
AB  - OBJECTIVES: Phaeochromocytoma may be either sporadic or part of a familial cancer
      syndrome. We have investigated whether there are differences between sporadic and
      MEN 2A phaeochromocytomas. DESIGN: A retrospective study. We analysed age at
      presentation, sex, mode of presentation, clinical data, laboratory and imaging
      techniques, treatment, pathology and follow-up. PATIENTS: Forty-six patients
      diagnosed with phaeochromocytoma between 1979 and 1995 (23 sporadic and 23
      familial) at the Hospital Universitario Virgen de la Arrixaca (Murcia, Spain), a
      tertiary referral centre. RESULTS: Mean age at presentation was 47 +/- 16 years
      for sporadic and 38 +/- 11 years for familial phaeochromocytoma (P < 0.05). The
      most common clinical feature and the presenting feature in cases of isolated
      phaeochromocytoma was hypertension. Of the MEN 2A patients, 52% were asymptomatic
      at diagnosis and only 35% presented with hypertension. Levels of adrenaline,
      noradrenaline, dopamine and metanephrines in a 24-hour urine connection confirmed
      the diagnosis in 95% of the isolated and 91% of the familial phaeochromocytomas.
      Computed tomography located 100% of the sporadic and 76% of the familial
      phaeochromocytomas (P < 0.02). All the MEN 2A phaeochromocytomas were bilateral
      compared with none of the sporadic phaeochromocytomas (P < 0.001). All the
      patients with familial phaeochromocytoma underwent bilateral adrenalectomy. The
      patients with sporadic phaeochromocytoma had the affected gland or the tumour, if
      extraadrenal, removed. CONCLUSIONS: In comparing sporadic and MEN 2A
      phaeochromocytoma we found differences in age at presentation, mode of
      presentation, clinical data, duration of clinical features, imaging findings
      bilaterality and type of surgical treatment required.

PMID- 9579233
TI  - Congenital hypothyroidism in Wales (1982-1993): demographic features, clinical
      presentation and effects on early neurodevelopment.
AB  - OBJECTIVE: Neonatal screening for congenital hypothyroidism (CH) was introduced
      in Wales in 1982. The aim of the study was to evaluate the demographic features
      and characteristics of infants identified during the first 12 years of screening
      and their neurodevelopmental progress in the first 2 years of life. DESIGN:
      Prospective collection of biochemical and clinical data (including results of
      Griffiths Mental Development Scales) obtained from questionnaires sent to
      paediatricians responsible for the ongoing clinical care of children with CH.
      PATIENTS: In Wales, between 1982 and 1993, 136 infants with primary congenital
      hypothyroidism (CH) were identified by the neonatal screening programme. RESULTS:
      Of all new-borns, 99.8% were screened and the prevalence of CH was 1 in 3279 (1
      in 2473 girls and 1 in 4770 boys). The prevalence of CH was increased in North
      Wales. CH was associated with increased birth weight (48.5% of infants weighed
      greater than 3.5 kg) and an increased prevalence of non-thyroidal congenital
      abnormalities (8%) and congenital heart disease (3%). Isotope scanning
      demonstrated an increased prevalence of normal or enlarged thyroid glands and
      fewer ectopic glands compared to those reported in other studies. The mean
      developmental quotients (DQs) for individual subsets of intellectual and
      behavioural functioning in children with CH aged 1 and 2 years were all above 100
      (range: 103.5-111.9). In subjects with absent thyroids, these DQs were correlated
      with the serum concentrations of free thyroxine before treatment. CONCLUSIONS:
      The demographic features of infants with congenital hypothyroidism born in Wales
      are similar to those reported from other European studies although there are
      marked regional variations in prevalence within Wales for which there is no
      apparent explanation. The median age of starting therapy was 17 days and compares
      favourably with other screening programmes. The overall mental development of
      Welsh children aged 1 and 2 years with congenital hypothyroidism identified by
      neonatal screening is satisfactory.

PMID- 9579234
TI  - Carrier status for steroid 21-hydroxylase deficiency is only one factor in the
      variable phenotype of acne.
AB  - OBJECTIVE: Previous endocrine studies of women with acne have produced diverse
      results. This study was designed to seek evidence, from endocrine and genetic
      studies, for impaired steroid biosynthesis in patients with acne. DESIGN: Adrenal
      stimulation tests with synthetic adrenocorticotrophic hormone (ACTH) were
      performed. MEASUREMENTS: Steroid hormones were measured basally and 30 minutes
      after ACTH. The results were correlated with analysis of the steroid 21
      hydroxylase gene (CYP21). PATIENTS: Fifty-one consecutive female patients (mean
      age 27.1 years) referred with acne. RESULTS: The median plasma 17
      hydroxyprogesterone (17-OHP) before and 30 minutes after ACTH were 2.5 nmol/l
      (range 1.1-8.2) and 7.3 (2.1-17.8) nmol/l which were significantly above normal
      female controls (n = 11, mean age 25.6 years) at 1.5 (0.9-4.2) and 4.6 (2.6-8.4)
      nmol/l. Eighteen of 51 acne patients showed an abnormal 17-OHP response. The 21
      hydroxylase gene (CYP21) was examined for major deletions and for three common
      point mutations in 31 of the patients (14 with exaggerated 17-OHP response). One
      patient had a deletion of CYP21 on one allele consistent with carrier status for
      the classical congenital adrenal hyperplasia (CAH). Five patients, one of whom
      had a normal 17-OHP response to Synacthen, were heterozygous for the val 281 leu
      mutation in exon 7 of the CYP21 and were therefore carriers for a mutation
      associated with late-onset CAH. One patient with a raised 17-OHP response was
      homozygous for the splice site mutation in intron 2 and one patient with a normal
      17-OHP response was heterozygous for the mutation. None of the patients had the
      ile 172 asn mutation. Eight of the 31 acne patients who had CYP21 gene analysis
      were carriers for mutations in the 21-hydroxylase gene but only six would have
      been detected by an abnormal response of 17-OHP on stimulation. CONCLUSION:
      Although alterations of the CYP21 gene were more common in acne than in controls
      there is a poor correlation between these events and raised steroids and acne.
      Factors other than mild impairment of CYP21 contribute to the variability of the
      clinical phenotype in hyperandrogenic states including acne.

PMID- 9579235
TI  - Direct effects of corticotrophin-releasing hormone on stimulated growth hormone
      secretion.
AB  - OBJECTIVE: This study evaluated the effect of corticotrophin-releasing hormone
      (CRH) on growth hormone releasing hormone (GHRH)-stimulated growth hormone (GH)
      release in man. DESIGN: Six healthy adult volunteers (age 20-35 years) were
      studied. On different occasions they each received an intravenous bolus of
      saline, CRH(1-41) (100 micrograms), adrenocorticotrophic hormone (ACTH)
      [Synacthen (500 ng/m2)] or hydrocortisone (50 mg), followed 30 minutes later by
      an intravenous bolus of either GHRH-(1-29)-NH2 (1.0 microgram/kg) or saline.
      MEASUREMENT: Serum GH concentrations were measured using an immunoradiometric
      assay, and cortisol concentrations were measured by commercial radioimmunoassay.
      TSH concentrations were measured using a solid phase immunoradiometric assay kit.
      RESULTS: Pretreatment with CRH(1-41) attenuated the GH response to GHRH
      [saline/GHRH-(1-29)-NH2 20.2 +/- 6.2 mU/l; CRH(1-41)/GHRH-(1-29)-NH2 10.9 +/- 2.8
      mU/l (P = 0.01)]. This effect was not due to the rise in ACTH or cortisol induced
      by CRH(1-41), since pretreatment with either ACTH or hydrocortisone significantly
      augmented the GH response to GHRH-(1-29)-NH2 in the same subjects [ACTH/GHRH-(1
      29)-NH2 30.3 +/- 8.8 mU/l (P = 0.01); hydrocortisone/GHRH-(1-29)-NH2 36.4 +/-
      11.2 mU/l (P = 0.02)]. CONCLUSION: Our data suggest that the inhibitory effect of
      CRH(1-41) on GHRH-(1-29)-NH2-induced GH release is not a result of ACTH or
      cortisol release but reflects a direct action of CRH on GH secretion, possibly
      via stimulation of somatostatin release. The acute rise in GH following
      glucocorticoid administration could be explained in part by a rapid suppression
      of endogenous CRH.

PMID- 9579236
TI  - Dexamethasone in the diagnostic work-up of growth hormone deficiency.
AB  - OBJECTIVE: Acute administration of dexamethasone (dexa) has recently been shown
      to induce growth hormone (GH) release. To ascertain the efficacy of this stimulus
      in assessing GH secretory status in children, we tested it in a large group of
      patients with short stature. METHODS: We administered dexamethasone at the dose
      of 2 mg/m2 to 44 short normal children and 19 GH deficient (GHD) children, either
      orally or intravenously and compared the results of the dexa-test to the more
      classical clonidine test. RESULTS: The oral dexa-test induced a GH peak similar
      to the clonidine test (clo) (controls clo: 23.8 +/- 7.8 mU/l, median 22.8, range
      15.2-45.4 vs. control dexa: 20.6 +/- 10.8, median 16.8, range 8-47, P = 0.2. GHD
      clo: 9.8 +/- 2.6, median 9.2, range 6.4-13.4 vs. GHD dexa: 9.4 +/- 3.4, median
      10.2, range 4.6-14, P = 0.8). Its sensitivity and specificity with respect to the
      clonidine test were 91% (10/11 GHD) and 65% (15/23 controls), respectively. The
      GH peak after i.v. dexa was smaller than that after clonidine (control clo: 30.6
      +/- 14 micrograms/l, median 24.8, range 14.2-62.4 vs. control dexa: 21.6 +/- 5.4,
      median 21.6, range 11.2-33, P = 0.01. GHD clo: 7.4 +/- 4.2, median 8.8, range 0.4
      11.8 vs. GHD dexa: 6.4 +/- 5.6, median 5.8, range 0.4-16.2, P = 0.17) with
      sensitivity and specificity of 87% (7/8 GHD) and 90% (19/21 controls),
      respectively. The lower potency of dexamethasone could account for these figures,
      since when a different cut-off was used (12 mU/l and 11 mU/l for the oral and
      i.v. route) both sensitivity and specificity were improved. More data are needed
      to support these findings and establish a clear cut-off. In the control group, no
      difference was found between GH peak after oral or i.v. dexa but GH-area under
      the curve (AUC) was larger for i.v. than for oral dexa. No side effects were
      noted. CONCLUSIONS: Intravenous dexamethasone appears to be a promising stimulus
      for the detection of GH deficiency in children, particularly for use in
      outpatients.

PMID- 9579237
TI  - Effect of replacement doses of thyroxine on bone mineral density.
AB  - INTRODUCTION: Hyperthyroidism is associated with a reduction in bone mineral
      density (BMD). Suppressive doses of thyroxine (T4), inducing subclinical
      hyperthyroidism, have been reported by some investigators to reduce BMD. Little
      work has been done on replacement doses of T4. AIM: The aim was to investigate
      the effect of replacement doses of T4 on BMD. STUDY DESIGN: Cross-sectional study
      of hypothyroid patients on long-term T4 replacement doses, comparing those who
      had primary hypothyroidism with those who were previously hyperthyroid. PATIENTS:
      Fifty women on replacement doses of T4 for more than 5 years were recruited.
      Twenty-five were treated for primary (group 1) and 25 for radioiodine-induced
      hypothyroidism (group 2). They were well matched for age, menstrual status,
      smoking history, body mass index (BMI), dose and duration of T4 replacement as
      well as thyroid status. MEASUREMENTS: BMD was assessed by dual energy X-ray
      absorptiometry. Free T4 (FT4), FT3 as well as ultrasensitive TSH assays were used
      to assess thyroid status. RESULTS: The two groups showed no difference in BMD
      (g/cm2) of the lumbar spine (1.008 vs. 0.957, P = 0.25), femoral neck (0.745 vs.
      0.735, P = 0.79) and total hip (0.878 vs. 0.837, P = 0.24). When the two groups
      were pooled, there was no significant difference between the patients and a
      reference population with femoral neck and total hip BMD expressed as a standard
      deviation (Z) score. However, the lumbar spine mean Z score was significantly
      greater than zero. For each site, there was a negative correlation of BMD with
      age in at least one group but, in general, BMI, FT4, FT3 and duration of T4
      replacement did not correlate with BMD. T4 dose, however, had a consistent
      positive correlation with BMD in the spine, femoral neck and the hip (P = 0.01,
      0.04 and 0.02, respectively) in group 2 but not group 1. CONCLUSION: In this
      study, there is no evidence for a difference in bone mineral density in patients
      receiving replacement doses of thyroxine irrespective of the aetiology of their
      hypothyroidism. The reduced bone mineral density associated with hyperthyroidism
      appears to be restored, maintained and in some cases possibly improved while on
      long-term thyroxine replacement post-radioiodine.

PMID- 9579238
TI  - Effect of food intake on the pharmacokinetics and antidiuretic activity of oral
      desmopressin (DDAVP) in hydrated normal subjects.
AB  - OBJECTIVE: The effect of food ingestion on the gastrointestinal absorption and
      antidiuretic action of oral desmopressin. An oral preparation of desmopressin, a
      synthetic analogue of vasopressin, has recently become available for clinical
      use. DESIGN: A randomized, single-blind, crossover study with four treatment
      arms. Day A, no meal + placebo; B, no meal + 400 micrograms oral desmopressin; C,
      standard meal + 400 micrograms oral desmopressin; D, standard meal + 400
      micrograms oral desmopressin after 1.5 hours. Plasma desmopressin was measured
      every 15-30 minutes for 6 hours after drug intake. An intravenous hydration
      regimen was employed on each study day. SUBJECTS: Sixteen healthy, non-smoking,
      mean aged 20-35 years (mean 27.8 years). MEASUREMENTS: Plasma desmopressin
      concentrations were measured throughout each study day to calculate the area
      under the desmopressin plasma-concentration-time curve to infinity (AUCinf), the
      maximum plasma desmopressin concentration (Cmax), the time at which Cmax was
      reached (Tmax) and the time at which plasma desmopressin was first detected
      (Tlag). Urine volume, urine osmolality and plasma sodium concentrations were also
      measured at specified times on each study day. RESULTS: The total absorption of
      oral desmopressin, reflected by the AUCinf, was significantly higher when taken
      during the fasting state (day B) compared with its administration with or 1.5
      hours after a standard meal (days C and D). In addition, Cmax was higher and both
      Tmax and Tlag were shorter on day B compared with days C and D. No effect of food
      ingestion was observed on the pharmacodynamics of oral desmopressin: urine volume
      was decreased and urine osmolality was increased to similar extents on all active
      treatment days (B, C and D). No significant reductions in plasma sodium
      concentrations (a safety parameter) was observed during the trial. CONCLUSIONS:
      The gastrointestinal absorption of desmopressin is reduced and delayed if
      administered with or 1.5 hours after a meal. This decreased absorption of
      desmopressin did not have an impact on the antidiuretic action of the drug since
      all treatment regimens elicted a maximal response. It is possible that
      administration of desmopressin in the fasting state may prolong its duration of
      action.

PMID- 9579240
TI  - "The patient is turned every 2 hours".

PMID- 9579239
TI  - Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a
      thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.
AB  - A 50-year-old male presented with diabetes mellitus and Cushing's syndrome
      associated with a large mediastinal mass. The levels of serum cortisol were high
      (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l)
      and urinary excretion of cortisol were also increased. The levels of these
      hormones did not change in response to stimulation with corticotrophin releasing
      hormone (CRH) or suppression with high doses of dexamethasone. The patient had an
      elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH
      releasing hormone (GHRH) in eight plasma samples were markedly increased (600
      1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY)
      were also increased. Computer-assisted tomography and octreotide scintigraphy
      revealed a large mediastinal tumour and metastases in the left supraclavicular
      fossa. During treatment with octreotide, the baseline GH level was decreased (to
      4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of
      the tumour tissue resulted in a further decrease in the baseline serum GH level
      to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height
      and mean GH were affected to a lesser extent. Postoperatively, circulating levels
      of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement.
      Histological examination showed a neuroendocrine tumour with characteristics
      consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH
      and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells
      and the three peptides appeared to be co-localized. In primary culture, cells
      from this tumour displayed calcium influx in response to GHRH or GH releasing
      peptide-6 (GHRP-6), while there were not such responses by cells from another
      carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case
      of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells
      were responsive to GHRH and GHRP-6 as well as octreotide.

PMID- 9579241
TI  - Characterization of the precipitants of hospitalization for heart failure
      decompensation.
AB  - BACKGROUND: The model for management of patients with heart failure may be a key
      determinant of morbidity and quality of life. Development of a better management
      strategy for these patients requires determination of the reasons for
      decompensation that leads to hospitalization. OBJECTIVES: To ascertain and rank
      the principal reasons for hospitalization of patients who have heart failure.
      METHODS: Retrospective audit of all 1992 admissions (N = 1031; 691 patients)
      coded for heart failure at a Veterans Affairs medical center and a tertiary care
      university medical center. RESULTS: The diagnosis of heart failure was verified
      by preset criteria in 72% of the patients. Of the 496 patients with documented
      heart failure, worsening heart failure was a main reason for admission in 390
      (79%). Despite different socioeconomic backgrounds, excessive sodium retention
      was the leading factor (55%) associated with decompensation in patients at both
      institutions. Other factors precipitated admission much less often. CONCLUSIONS:
      Many hospitalizations for heart failure might be avoided by case management
      directed at lessening sodium overload. Increased use of medications known to be
      effective in persons with heart failure (angiotensin-converting enzyme
      inhibitors, digoxin, and adequate diuretic therapy) might reduce the likelihood
      of decompensation. Implementation of behavioral interventions to assist patients
      with self-monitoring signs of sodium retention and to improve compliance with
      medications and dietary sodium restrictions are strategies for further reducing
      the risk of decompensation.

PMID- 9579243
TI  - Bedside monitoring of the QT interval.
AB  - Cardiac repolarization, represented on the ECG by the QT interval, is of
      particular clinical interest in critical care. Once it is measured and corrected
      for changes in heart rate, the QT interval is known as the QTc. Measurement of
      the QT interval is important because a prolonged QT interval is associated with
      ventricular tachycardia and sudden cardiac death. Despite the serious
      complications associated with a prolonged QT interval, the interval is not
      routinely measured because a standardized method for measuring it has not been
      established and the length of QT interval critical to the development of
      ventricular tachycardia has not been determined. Much has been written about the
      conditions associated with prolonged QT intervals and specific actions to take
      when complications appear. Guidelines to be used for QT analysis in the clinical
      area, based on currently available information, include (1) procedures for
      measuring QT interval and calculating QTc, (2) procedures for QT analysis, (3)
      warning signs that indicate increased risk of ventricular tachycardia associated
      with a prolonged QT interval, and (4) actions to consider once increased risk is
      determined.

PMID- 9579242
TI  - Women and coronary disease: relationship between descriptors of signs and
      symptoms and diagnostic and treatment course.
AB  - BACKGROUND: Heart disease is the No. 1 killer among women in the United States.
      Differences in the clinical features of coronary heart disease among men and
      women have been reported, along with various approaches to the diagnostic workup
      and therapeutic interventions. PURPOSE: To explore the relationship between
      descriptors of signs and symptoms of coronary heart disease and follow-up care
      and to investigate any differences between male and female patients. METHODS:
      Structured interviews with patients and chart audits were used to assess initial
      signs and symptoms, associated cardiac-related signs and symptoms, and the
      diagnostic tests and interventions used for treatment. The sample consisted of 98
      patients (51 women and 47 men) who were admitted with a medical diagnosis of
      myocardial infarction. RESULTS: Chest pain was the most common sign or symptom
      reported by both men and women. The 4 most common associated signs and symptoms
      were identical in men and women: fatigue, rest pain, shortness of breath, and
      weakness. However, significantly more women than men reported loss of appetite,
      paroxysmal nocturnal dyspnea, and back pain. Women were also less likely than men
      to have angiography and to receive i.v. nitroglycerin, heparin, and thrombolytic
      agents as part of acute management of myocardial infarction. CONCLUSION: Chest
      pain remains the initial symptom of acute myocardial infarction in both men and
      women. However, women may experience some different associated signs and symptoms
      than do men. Despite these similarities, men still are more likely than women to
      have angiography and to receive a number of therapies.

PMID- 9579244
TI  - The safety of automatic versus manual blood pressure cuffs for patients receiving
      thrombolytic therapy.
AB  - BACKGROUND: Patients receiving thrombolytic therapy for acute myocardial
      infarction require frequent monitoring of blood pressure. Historically, many
      nurses have been reluctant to use automatic blood pressure cuffs during
      thrombolytic therapy because of concern that the automatic cuffs might increase
      risk of bleeding. This concern is not based on research findings but on case
      reports, anecdotal observations, and possible myths in clinical practice.
      OBJECTIVE: To determine the safety of using automatic blood pressure cuffs during
      thrombolytic therapy in patients with acute myocardial infarction. METHODS:
      Ninety-six patients with acute myocardial infarction who received thrombolytic
      therapy (streptokinase or tissue plasminogen activator) were randomized to have
      blood pressure measurements obtained with either automatic or manual blood
      pressure cuffs. Patients were checked at least every 2 hours for purpuric lesions
      (petechiae, ecchymoses, or hematomas). The study ended after 24 hours of
      measurements or when a purpuric lesion was noted. RESULTS: We found no
      significant difference in frequency of purpuric lesions between patients who had
      blood pressure measured with a manual cuff and patients who had blood pressure
      measured with an automatic cuff. The most common purpuric lesions noted were
      ecchymoses. A significant difference was noted in the frequency of purpuric
      lesions depending on which thrombolytic agent was used, regardless of cuff type.
      CONCLUSIONS: Automatic blood pressure cuffs are as safe as manual blood pressure
      cuffs in patients with acute myocardial infarction who are receiving thrombolytic
      therapy.

PMID- 9579245
TI  - Time of removal of femoral sheaths after interventional procedures: comparison of
      hemoglobin and hematocrit values.
AB  - BACKGROUND: Few investigators have examined the time of removal of femoral
      sheaths after interventional procedures and its effect on patients' hematocrit
      and hemoglobin levels. OBJECTIVE: To determine if hematocrit and hemoglobin
      values differed significantly according to the length of time femoral sheaths
      remained in place after interventional procedures. METHODS: After a review of the
      literature, data were collected on a convenience sample consisting of 2 groups.
      Patients in group 1 (n = 30) had femoral sheaths removed within 3.5 to 9.0 hours
      (mean, 5.5 hours) after an interventional procedure. Patients in group 2 (n = 30)
      had the sheaths removed within 17 to 36 hours (mean, 22 hours) after an
      interventional procedure. Blood samples were obtained from all patients before
      the interventional procedure (baseline values) and again 1 day after the
      procedure. Patients in group 1 had sheaths removed before the second blood sample
      was obtained; patients in group 2 did not. Data were analyzed by using an equal
      variance t test to determine if hematocrit and hemoglobin values differed
      significantly between the 2 groups. RESULTS: Hematocrit and hemoglobin values the
      day after interventional procedure differed significantly in the two groups.
      CONCLUSION: Earlier removal of femoral sheaths may have a beneficial
      physiological effect. The results indicate that prompt removal of femoral sheaths
      after interventional procedures improves patients' outcomes.

PMID- 9579246
TI  - Validity of the numeric rating scale as a measure of dyspnea.
AB  - BACKGROUND: Dyspnea, a devastating sign, is rarely monitored by clinicians. One
      reason may be the lack of a valid measurement scale that is easy to use in a
      clinical setting. OBJECTIVES: To establish the validity of the numeric rating
      scale as a measure of present dyspnea (dyspnea at rest). METHODS: A total of 188
      patients with chronic obstructive pulmonary disease rated their present dyspnea
      by using the Visual Analog Dyspnea Scale and the numeric rating scale. They also
      rated their usual dyspnea (dyspnea during the past week). Demographic information
      was collected from each patient's chart, and pulmonary status was assessed with
      portable spirometry, pulse oximetry, or both. RESULTS: Concurrent validity of the
      numeric rating scale was supported by the high correlation of its scores with
      scores from the Visual Analog Dyspnea Scale. Conversion of the numeric rating
      scale to a 0-to-100 scale and comparison with the visual analog scale (by using a
      paired t test to determine if the correlated scores were similar for clinical
      decision making) showed that scores were not significantly different. A paired t
      test showed a difference in scores on the numeric rating scale obtained before
      and after ambulation, supporting the construct validity of the numeric rating
      scale. Scores on the numeric rating scale for present dyspnea were poorly
      correlated with ratings of usual dyspnea, indicating that present dyspnea and
      usual dyspnea are different constructs. CONCLUSION: Present and usual dyspnea are
      different constructs. The numeric rating scale is a valid measure of present
      dyspnea.

PMID- 9579247
TI  - Effect of neuromuscular blockers and opiates on the cerebrovascular response to
      endotracheal suctioning in adults with severe head injuries.
AB  - BACKGROUND: Intracranial hypertension occurs in response to routine procedures
      such as endotracheal suctioning in patients with severe head injuries. In some
      patients, the intracranial pressure does not immediately return to baseline
      levels. OBJECTIVES: To examine the effect of drug administration on
      cerebrovascular response to endotracheal suctioning in adults with severe head
      injuries. METHODS: Seventy-one subjects were divided into 3 groups: those who
      received no drugs, those treated with opiates only (morphine sulfate and fentanyl
      citrate), and those treated with a neuromuscular blocking agent (vecuronium
      bromide) plus opiates. A controlled protocol involving 2 sequences of
      endotracheal suctioning that included hyperoxygenation, hyperinflation, and
      suctioning was used for all subjects. Two-way repeated-measures analyses of
      variance were done with type of drug as the between-subject factor and phase of
      suctioning as the within-subject factor. Survival analysis was used to compare
      the return of intracranial pressure to baseline levels among the 3 groups.
      RESULTS: Changes in intracranial pressure were significantly smaller in subjects
      who received a neuromuscular blocking agent plus opiates than in subjects who did
      not receive any drugs or received opiates only. The greatest increase in
      intracranial pressure from baseline was in the first and second phases of
      suctioning. The 3 groups showed no significant difference in the return of
      intracranial pressure to baseline level. CONCLUSIONS: Neuromuscular blockers
      attenuate the increases in intracranial pressure that occur with endotracheal
      suctioning. It is not known whether control of procedurally induced elevations in
      intracranial pressure affects long-term outcomes in adults with severe head
      injuries.

PMID- 9579249
TI  - Treatment interference in acutely and critically ill adults.
AB  - OBJECTIVES: To examine the state of knowledge of treatment interference, the self
      removal of technological devices, in acutely or critically ill adults and to
      propose a multidisciplinary research agenda to further understanding of this
      clinical problem. METHOD: A combined computerized and hand search of the nursing
      and medical literature (MEDLINE, 1966 to June 1996; Cumulative Index to Nursing
      and Allied Health Literature, 1985 to June 1996; and holdings at the Center for
      the Study of Nursing History at the University of Pennsylvania) was conducted.
      Literature on specific technological devices and articles that contained the
      terms self-removal, withdrawal, devices, self-extubation, unplanned extubation,
      and involuntary treatment were searched. RESULTS: Literature on treatment
      interference was found in four main topic areas: (1) maintaining treatment, (2)
      unplanned extubation, (3) disruption or manipulation of a medical device, and (4)
      involuntary treatment. CONCLUSIONS: The results clearly establish the clinical
      importance of treatment interference and underscore the multidisciplinary and
      multifactorial nature of this perplexing, life-threatening clinical problem.
      Future research on treatment interference should emphasize systematically
      building an understanding of the processes involved, including patients'
      attributes, behavioral cues, and consequences, to develop appropriate
      multidisciplinary strategies to prevent patients' self-removal of technological
      devices.

PMID- 9579248
TI  - Nurses' knowledge of advance directives.
AB  - BACKGROUND: The Patient Self-Determination Act offers persons the opportunity to
      make their end-of-life choices known by the use of advance directives. Although
      nurses are designated advocates for patients and are available to communicate
      patients' concerns and wishes to other healthcare providers, few data on nurses'
      knowledge of advance directives have been reported. OBJECTIVE: To describe
      nurses' knowledge of advanced directives. SAMPLE: A volunteer sample of 339 RNs
      in a 600-bed acute care teaching hospital was surveyed. The sample represents 38%
      of the approximately 900 nurses employed at this hospital. METHODS: Data obtained
      from a 44-item questionnaire that tested nurses' knowledge of advance directives
      were analyzed. In addition, the relationship between nurses' knowledge of advance
      directives and certain demographic factors was analyzed. RESULTS: The mean score
      for knowledge of advance directives was 78% correct answers. Fifty-five percent
      of the respondents indicated that they did not have a good understanding of
      advance directives. Only 14% had completed these end-of-life documents for
      themselves, and 92% indicated that further education would increase their
      understanding of advance directives. An analysis of variance produced only one
      significant finding: the relationship between ethnicity and knowledge about
      advance directives. CONCLUSIONS: Nurses must increase their knowledge of advance
      directives. Results of this survey should stimulate caregivers and hospital
      policy makers to take a long-range view of their responsibilities to patients
      regarding advance directives and their responsibilities for educating the persons
      who convey information about advance directives to patients.

PMID- 9579250
TI  - Hypokalemic periodic paralysis: a case study.

PMID- 9579251
TI  - Fifty percent of patients with coronary artery disease do not have any of the
      conventional risk factors.
AB  - Prinzmetal's variant angina, primarily a vasospastic disease, is a glaring
      example of the gaps in our knowledge regarding the etiology of coronary heart
      disease. Half of all patients with coronary heart disease do not have any of the
      established coronary risk factors. Prinzmetal's variant angina, syndrome X,
      coronary embolization, and congenital coronary anomalies, are a few examples of
      conditions that may not be associated with established risk factors. New risk
      factors that are emerging in an attempt to establish an etiology in this group of
      patients are homocysteine plasma fibrinogen, estrogen-deficiency lipoprotein (a),
      C-reactive protein, Chlamydia pneumoniae, factor VII endogenous tissue
      plasminogen, and endogenous plasminogen activator/inhibitor type I. The battle
      against cardiovascular disease continues!

PMID- 9579252
TI  - Health practices of critical care nurses: are these nurses good role models for
      patients?

PMID- 9579253
TI  - The impact of DNR orders on nursing workload in an ICU.

PMID- 9579254
TI  - Ischaemia-reperfusion: time to increase our awareness during anaesthesia.

PMID- 9579255
TI  - Closure of persistently patent arterial duct and its impact on cerebral
      circulatory haemodynamics in children.
AB  - PURPOSE: Closure of a patent arterial duct (PDA) is suggested as a risk factor
      associated with intraventricular haemorrhage and/or cerebral ischemia in
      neonates. This study evaluate the effects of transcatheter closure of a patent
      arterial duct in children on cerebral blood flow velocity. METHODS: Twelve
      children, aged from one to eight years were enrolled. Anaesthesia induction
      consisted of thiopentone, fentanyl and diazepam. Tracheal intubation was
      facilitated with vecuronium. Anaesthesia was maintained with N2O 70% in O2 and a
      PaCO2 between 35 to 40 mmHg. No cerebral vasoactive agents were used. Mean
      arterial pressure (MAP), central venous pressure (CVP), heart rate were
      continuously recorded. Systolic (Vs) and diastolic (Vd) cerebral blood flow
      velocity (CBFV) were recorded. Cerebral perfusion pressure (CPP) was calculated.
      The mean CBFV, the systolic-mean ratio and the cerebral blood volume were
      estimated from the area under the velocity-time curve (AUC) before PDA closure,
      immediately after and for 10 min following occlusion. RESULTS: The mean (+/- SD)
      age and weight were 30 +/- 22 mo and 13 +/- 5 kg, respectively. Continuous
      recording during duct closure showed an abrupt increase in Vd (P < 0.05) whereas
      Vs remained constant. The AUC increased after closure and persisted for 10 min (P
      < 0.05). CONCLUSION: This study confirms that closure of a PDA leads to acute
      changes in intracerebral diastolic flow and volume. This observation gives weight
      to mechanisms involved in IVH in smaller infants after arterial surgical duct
      closure. The anaesthetic technique used for arterial duct closure in these
      procedure could influence these observations.

PMID- 9579256
TI  - Gas leak and gastric insufflation during controlled ventilation: face mask versus
      laryngeal mask airway.
AB  - PURPOSE: To compare two airway management techniques, face mask (FM) with
      oropharyngeal airway and laryngeal mask airway (LMA), with respect to the
      effectiveness of positive pressure ventilation and airway maintenance. METHODS:
      After induction of anaesthesia, two airway management techniques (FM or LMA) and
      three peak pressures (20, 25 and 30 cm H2O) were randomly applied during
      controlled ventilation in 60 patients. Data collected included inspiratory and
      expiratory volumes and presence of gastro-oesophageal insufflation. Leak was
      calculated by subtracting the expiratory from the inspiratory volume, expressed
      as a fraction of the inspiratory volume. RESULTS: Expiratory volumes (mean +/-
      SD) at 20, 25 and 30 cm H2O for LMA ventilation were 893 +/- 260, 986 +/- 276 and
      1006 +/- 262 respectively, and for FM ventilation 964 +/- 264, 1100 +/- 268 and
      1116 +/- 261. Leak fractions at 20, 25 and 30 cm H2O for LMA ventilation were
      0.21 +/- 0.15, 0.24 +/- 0.18 and 0.26 +/- 0.18 respectively, and for FM
      ventilation 0.14 +/- 0.09, 0.14 +/- 0.09 and 0.12 +/- 0.08. The frequency of
      gastro-oesophageal insufflation was 1.6%, 5% and 5% for the LMA and 5%, 15% and
      26.6% for the FM for ventilation pressures of 20, 25 and 30 cm H2O respectively
      which was greater with LMA use. CONCLUSION: Ventilation was adequate in all
      patients using both techniques. Leak was pressure dependent and greater with LMA
      use. Most of the leak was vented to the atmosphere via the pharynx. Gastro
      oesophageal insufflation was more frequent with ventilation using the face mask.
      LMA use with positive pressure ventilation would appear to be a better airway
      management method than the face mask.

PMID- 9579257
TI  - Potency and hourly maintenance requirement of combinations of mivacurium and
      pancuronium in adults.
AB  - PURPOSE: To evaluate the dose-response and maintenance requirements of a
      combination of mivacurium and pancuronium (cMP) in clinical practice. METHODS: In
      a randomised, open clinical study, 70 patients, 17-50 yr of age, were
      anaesthetised with propofol, alfentanil and nitrous oxide in oxygen. Thirty
      patients received mivacurium and 20 patients received pancuronium to establish
      dose-response curves for these agents. Hourly maintenance requirements of
      mivacurium and pancuronium to maintain 90-95% neuromuscular blockade (NMB) were
      determined. Thereafter, 20 additional patients received cMP in incremental doses
      to establish a cumulative dose-response curve for cMP followed by maintenance
      doses of cMP. NMB was recorded by adductor pollicis electromyography. RESULTS:
      The ED95 values for mivacurium and pancuronium were 100 and 66 micrograms.kg-1,
      respectively; and for the cMP 2:1 (in mg:mg basis), 32 micrograms.kg-1 mivacurium
      together with 16 micrograms.kg-1 pancuronium. This cMP was 1.8 times more potent
      than one parent agent (P < 0.0001). When cMP 2:1 was used, 60% of normal
      maintenance requirement of pancuronium reduced the requirement of mivacurium by >
      90%. If cMP 20:1 was used, then 20% of normal maintenance requirement of
      pancuronium reduced the requirement of mivacurium by > 70%. Neostigmine 35
      micrograms.kg-1 given at T1 10% recovery following cMP reversed the NMB to a TOF
      ratio of 0.70 in 9.5 +/- 3.9 min. CONCLUSION: These results reflect considerable
      synergism between mivacurium and pancuronium. The cMP is near intermediate-acting
      and the NMB is easily reversed with neostigmine. By using cMP, it may be possible
      to save some pharmacological costs during maintenance of anaesthesia.

PMID- 9579258
TI  - Analgesia in day case breast biopsy--the value of pre-emptive tenoxicam.
AB  - PURPOSE: Inadequate analgesia is a major problem following ambulatory surgery. In
      this prospective randomised study, the use of pre-operative intravenous tenoxicam
      (a non steroidal anti-inflammatory agent) was compared with post-incision
      tenoxicam for the relief of post-operative pain in 77 patients undergoing day
      case breast biopsy. METHODS: All patients received a standard general anaesthetic
      which included infiltration of the wound with bupivacalne after skin closure.
      Intravenous tenoxicam (20 mg) was administered as a single bolus either 30 min
      before surgery (37 patients) or after incision (40 patients). Pain scores (100 mm
      visual analog scale) were obtained at 30, 60, 120 and 240 min after surgery
      analgesic requirements recorded. RESULTS: Both groups of patients were similar
      with respect to age, weight, operative time and length of the incision. Patients
      receiving the tenoxicam 30 min before surgery had lower pain scores at 30 min (22
      +/- 3) vs 46 +/- 3; P < 0.0001), 60 min (9 +/- 2 vs 28 +/- 3); P < 0.0001), 120
      min (6 +/- 2 vs 16 +/- 3); P = 0.0002) and 240 min (3 +/- 1) vs 7 +/- 2); P =
      0.02) post-operatively. They had a longer time to first analgesia (55.1 +/- 4.6
      vs 29.6 +/- 2.6) min; P = 0.0004), required less meperidine (5.4 +/- 2.6 vs 18.8
      +/- 3.9) mg; P = 0.007) and were more likely not to require any further analgesia
      during the first four hours post-operatively. CONCLUSION: Pre-operatively
      administered tenoxicam provides superior post-operative analgesia than tenoxicam
      administered after surgical incision in patients undergoing breast biopsy.

PMID- 9579259
TI  - SIADH following laparoscopic cholecystectomy.
AB  - PURPOSE: To present an unusual case of inappropriate antidiuretic hormone
      secretion syndrome after a minor surgical procedure in a healthy patient.
      CLINICAL FEATURES: A 71-yr-old woman underwent uneventful laparoscopic
      cholecystectomy for gallstones under general anaesthesia. Fifty-two hours post
      operatively she began convulsing and was found to have a serum sodium
      concentration as low as 112 mmol.L-1. Serum osmolality, urinary sodium
      concentration and urine osmolality suggested a diagnosis of inappropriate
      antidiuretic hormone secretion. Subsequent treatment with anticonvulsants
      followed by strict fluid restriction which increased serum sodium concentrations
      led to rapid recovery. CONCLUSION: The syndrome of inappropriate ADH secretion
      has several well documented causes including major surgery. Few episodes have
      been described following minor surgery in healthy patients and the only possible
      risk factor evident in this patient could be her advancing years.

PMID- 9579260
TI  - Superoxide radical generation and histopathological changes in hippocampal CA1
      after ischaemia/reperfusion in gerbils.
AB  - PURPOSE: We investigated the relationship between the generation of superoxide
      radicals and histopathological changes on delayed neuronal death in the
      hippocampal CA1 subfield. METHODS: Seventy gerbils were randomly assigned to two
      groups, a sham group and an ischaemia/reperfusion (I/R) group. In the I/R group,
      transient forebrain ischaemia was induced by occluding the bilateral common
      carotid arteries for four minutes. The cerebrum was removed after reperfusion at
      intervals of one minute, six, twelve and twenty-four hr and at three, five and
      seven days. Each forebrain was cut into two portions including the hippocampus.
      The quantity of superoxide radicals was measured by using chemiluminescence, and
      histopathological changes in the hippocampal CA1 subfield were examined. RESULTS:
      In the I/R group, superoxide radicals increased on the 3rd and 5th days compared
      with the sham group (16.1 +/- 3.4 vs 3.2 +/- 1.0 on the third day (P < 0.0001);
      10.9 +/- 1.9 vs 3.3 +/- 0.8 on the fifth day (P < 0.0001)). In the I/R group, the
      pyramidal cells were atrophic and pycnotic; vacuolation, and structural
      disruption of the radial striated zone were observed from the third through the
      seventh day. In the sham group, these changes were not observed. There were
      differences of degenerative ratios in the pyramidal cells between the two groups
      from the third to seventh days (5.6 +/- 2.0 vs 80.9 +/- 3.3 on the third day (P <
      0.05); 6.9 +/- 0.4 vs 93.6 +/- 2.4 on the fifth day (P < 0.05); 6.2 +/- 1.5 vs
      95.0 +/- 1.3 on the seventh day (P < 0.05)). CONCLUSION: There is a correlation
      between the generation of superoxide radicals and histopathological changes of
      the pyramidal cells in the hippocampal CA1 subfield.

PMID- 9579261
TI  - Propofol enhances red cell antioxidant capacity in swine and humans.
AB  - PURPOSE: To determine the effect of an anaesthetic with antioxidant potential,
      propofol, on red blood cell (RBC) antioxidant enzyme activities and RBC
      susceptibility to peroxidative challenge. METHODS: Propofol was administered by
      intravenous bolus (2.5 mg.kg-1) and continuous infusion (36 and 72 ml.hr-1 in
      nine swine; 216 ml.hr-1 in two swine), to achieve serum concentrations between 5
      and 30 micrograms.ml-1 for two hours at each rate. Arterial blood sampling was at
      0, 10, 30, 60, and 120 min for each rate of infusion, for measurement of plasma
      propofol concentration, activities of plasma and RBC superoxide dismutase,
      glutathione peroxidase, glutathione reductase, RBC catalase, and RBC
      malondialdehyde (MDA) formation in response to ex vivo oxidative challenge with t
      butyl hydrogen peroxide (tBHP; 1.5 mM). Antioxidant mechanisms were determined by
      in vitro study of MDA formation, GSH depletion, and oxidation of haemoglobin to
      methaemoglobin in human erythrocytes exposed to propofol 0-75 microM. The
      antioxidant potential of propofol was compared with that of alpha-tocopherol
      utilising the reaction with 2,4,6-tripyridyl-s-triazine (TPTZ). RESULTS: Propofol
      had no effect on plasma or RBC antioxidant enzyme activities. It inhibited RBC
      MDA production over the range of 0-20 micrograms.ml-1 (y = -18.683x + 85.431; R2
      = 0.8174). Effective propofol concentrations for 25% and 50% reductions in MDA
      levels were 7-12 and 12-20 micrograms.ml-1, respectively. Propofol has a similar
      effect on human erythrocytes in vitro (R2 = 0.98). CONCLUSION: Propofol
      antagonises the effects of forced peroxidation of red cells at anaesthetic and
      sub-anaesthetic concentrations in swine. Its actions include scavenging of oxygen
      derived free radicals in a tocopherol-like manner.

PMID- 9579262
TI  - Suppressive actions of volatile anaesthetics on the response capability in cats.
AB  - PURPOSE: Suppression of response to a given stimulus by anaesthetics might be
      considered as a summation of the suppression of basal (pre-stimulus) activity and
      response capability (increased by stimulus). Anaesthetic suppression of each
      component in brain and cardiovascular variables by halothane, isoflurane or
      sevoflurane was compared in cats. METHODS: Thirty cats were allocated to one of
      three groups (n = 10 in each) according to the anaesthetic given. The sciatic
      nerve was stimulated after maintaining the end-tidal concentration of the
      anaesthetic at 1.3 or 2.0 MAC for at least 30 min. Cortical electroencephalogram
      (EEG), multi-unit activity in the mid-brain reticular formation (R-MUA), mean
      arterial pressure (MAP) and heart rate (HR) were measured before and after
      electrical sciatic nerve stimulation. RESULTS: The EEG patterns and R-MUA
      indicated greater suppression of activity in the brain by isoflurane (31 +/- 4%
      of awake state at 1.3 MAC, mean +/- SEM) and sevoflurane (38 +/- 5%) than by
      halothane (61 +/- 5%, P < 0.05), before stimulation. The R-MUA following the
      stimulation was not different among agents. The MAP and HR were not different
      among groups before stimulation, but following stimulation were greater in the
      sevoflurane group (137 +/- 9 and 103 +/- 9 mmHg at 1.3 and 2.0 MAC) than in the
      halothane group (103 +/- 5 and 76 +/- 3 mmHg, P < 0.05). CONCLUSION: Isoflurane
      and sevoflurane have greater suppressive action on the basal CNS activity than
      halothane at the same MAC, and that these two anaesthetics have a weak
      suppressive action on the response capability to peripheral stimulation.

PMID- 9579264
TI  - Fastrach--a new intubating laryngeal mask airway: successful use in patients with
      difficult airways.
AB  - PURPOSE: The Laryngeal Mask Airway-Fastrach (Fastrach) is a new modified
      laryngeal mask with the capability for guided tracheal intubation while
      maintaining ventilation. We report the use of this device in patients with proven
      difficult airways, following induction of general anaesthesia. CLINICAL FEATURES:
      After induction of general anaesthesia, having failed tracheal intubation with
      conventional laryngoscopy, the first patient's trachea was intubated via the
      Fastrach with fibreoptic guidance. In the second and third patients, who had
      documented histories of difficult tracheal intubation, tracheal intubation was
      performed electively with the Fastrach following induction of inhalational
      anaesthesia with spontaneous respiration. CONCLUSION: The Fastrach is an option
      in the management of the airway following failed tracheal intubation or for
      elective tracheal intubation in patients with anatomically difficult airways.

PMID- 9579263
TI  - Dantrolene inhibits nitric oxide synthase in rat alveolar macrophages treated
      with lipopolysaccharide and interferon-gamma.
AB  - PURPOSE: To examine the effects of dantrolene on nitric oxide (NO) production and
      on the activity and protein expression of inducible nitric oxide synthase (iNOS)
      induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma) in rat
      alveolar macrophages. METHODS: Pulmonary alveolar macrophages isolated from
      Sprague-Dawley rats were used. After incubation of macrophages with dantrolene (1
      to 100 microM) and LPS (1 microgram.ml-1) and IFN-gamma (100 u.ml-1) for 24 hr,
      the cell-free medium was removed for measuring the nitrite and tumour necrosis
      factor-alpha (TNF-alpha) levels by Griess reaction and ELISA kit, respectively.
      The harvested macrophages were also used to determine the activity of iNOS by
      using the conversion of [3H]-L-arginine to [3H]-L-citrulline method. Protein
      expression of iNOS was detected by Western blot analysis. RESULTS: In rats
      alveolar macrophages, (i) dantrolene (1 to 100 microM) caused a dose-dependent
      suppression of the production of nitrite and TNF-alpha induced by LPS (1
      microgram.ml-1) plus IFN-gamma (100 u.ml-1) and (ii) dantrolene (100 microM)
      inhibited the activity (by 37 +/- 5%, P < 0.01) and protein expression (by 39 +/-
      12%, P < 0.01) of iNOS in response to LPS plus IFN-gamma. CONCLUSION: Dantrolene
      inhibits NO production as well as the activity and expression of iNOS in alveolar
      macrophages treated with LPS plus IFN-gamma, which may be associated with the
      reduction of TNF-alpha production.

PMID- 9579265
TI  - Intubation via the LMA using a Cook retrograde intubation kit.
AB  - PURPOSE: We report two cases of difficult intubation where a laryngeal mask
      airway (LMA) was used and changed to a conventional endotracheal tube using a
      retrograde intubation set. CLINICAL FINDINGS: In two patients, following
      induction of anaesthesia, the trachea could not be intubated in the conventional
      fashion with a blade. In both patients an LMA was inserted to achieve an airway.
      In both patients intubation with a conventional endotracheal tube was required. A
      Cook Retrograde Intubation Kit and fibreoptic bronchoscope were used to change
      the LMA to conventional endotracheal tube without problems. CONCLUSION: The Cook
      retrograde intubation allows an LMA to be replaced with an endotracheal tube with
      an ID greater than 6 mm with a #3 or 7 mm with a #5 LMA. This technique places an
      exchange stylet into the airway which is superior to a conventional guidewire.
      This method allows the airway to be maintained until the LMA is exchanged with an
      endotracheal tube. Anaesthesia may be maintained and the airway instrumented
      without difficulty using this technique.

PMID- 9579266
TI  - Triggering delay time and work of breathing in three paediatric patient-triggered
      ventilators.
AB  - PURPOSE: To compare the effectiveness of three patient-triggered ventilators by
      evaluating triggering delay time and pressure-volume loops during initiation of
      inspiration. METHODS: In a two-part study, a model lung was used in part 1 and 20
      children, after tracheal intubation, in part 2. Triggering delay time and work of
      breathing (WOB) during pressure support ventilation using three patient-triggered
      ventilators: Servo Ventilator 300, VIP Bird, and SLE 2000 Neonatal Ventilator.
      Triggering delay time was from the beginning of negative deflection in the
      oesophageal pressure trace, to the onset of inspiration. The WOB was estimated
      directly by measuring the oesophageal pressure-volume loop. RESULTS: The Servo
      demonstrated superior triggering delay time and reduced WOB in the model study.
      The VIP Bird demonstrated shorter triggering delay and reduced WOB in the
      clinical component of the study. In the model lung, triggering delay time in the
      Servo 300 [62 +/- 6 msec (mean +/- SD)] was shorter than that in the VIP Bird (76
      +/- 7 msec) (P < 0.05), and WOB with the SLE 2000 (202 +/- 37 g.cm) was greater
      than with other ventilators, (Servo 300, 112 +/- 32 g.cm and VIP Bird 72 +/- 41
      g.cm) (P < 0.05). In the clinical study, triggering delay time in the VIP Bird
      (52 +/- 19 msec) was shorter than in the other ventilators, Servo 300 (66 +/- 14
      msec), SLE 2000 (68 +/- 65 msec) (P < 0.05). The Servo 300 (56 +/- 34 g.cm)
      required higher WOB than the other ventilators: VIP Bird (22 +/- 12 g.cm), SLE
      2000 (14 +/- 3 g.cm) (P < 0.05). CONCLUSION: Comparative model lung performance
      of these ventilators does not correspond with their clinical performance. In our
      clinical evaluation, the VIP Bird ventilator demonstrated superior performance
      with shorter triggering delay time, low WOB needed to initiate inspiration, and
      little air leak.

PMID- 9579267
TI  - Emergency tracheal intubation of patients lying supine on the ground: influence
      of operator body position.
AB  - PURPOSE: To evaluate the influence of operator body position during emergency
      intubation of patients lying on the ground. METHODS: This study was carried out
      in the prehospital setting by French mobile intensive care units. Two operator
      body positions (left lateral decubitus and kneeling) for emergency intubation of
      patients lying supine on the ground were compared in a observational prospective
      study. Each operator completed a questionnaire regarding conditions of intubation
      after patient completion. RESULTS: The incidence of laryngoscopic difficulty was
      lower in the left lateral decubitus group compared to the kneeling group (11.1%
      vs 26.9% respectively; P < 0.01). The number of attempts required for successful
      intubation was (P < 0.05) higher in the kneeling group than in the left lateral
      decubitus group. CONCLUSION: Emergency tracheal intubation of supine patients on
      the ground may be greatly facilitated by the use of the left lateral decubitus
      position of the operator.

PMID- 9579268
TI  - Anaphylactoid reaction to pentastarch.
AB  - PURPOSE: To report a probable anaphylactoid reaction to pentastarch, a low
      molecular weight hydroxyethyl starch (HES) colloid solution. CLINICAL FEATURES:
      Following a closed head injury, an 18-yr-old male was admitted to the Intensive
      Care Unit. Therapy was directed towards control of intracranial pressure (ICP)
      and maintenance of cerebral perfusion pressure (CPP). In the first 12 hr after
      admission, he had received 2500 ml polygeline (Haemaccel, Hoechst Marion Roussel
      Ltd.) and a dopamine infusion (up to 10 micrograms.kg-1.min-1) titrated to
      achieve a mean arterial pressure (MAP) of > or = 80 mmHg. Subsequent failure to
      achieve the target MAP resulted in commencement of a noradrenaline infusion (2.67
      micrograms.min-1), and rapid administration of 500 ml pentastarch (Pentaspan,
      DuPont Pharmaceuticals). During the HES infusion, marked hypotension (MAP < 60
      mmHg) developed associated with marked truncal urticaria. The hypotension was
      resistant to escalation of noradrenaline to 36 micrograms.min-1. Haemodynamic
      stability was rapidly restored and maintained with adrenaline boluses (total 450
      micrograms) and infusion (1.67 micrograms.min-1). The remainder of the patient's
      ICU and hospital stay was unremarkable. A serum tryptase drawn in the first 40
      min of the reaction was not elevated. Other biochemical markers were not assayed.
      Skin testing has not been carried out. CONCLUSION: The temporal relationship and
      clinical manifestations observed in this case, together with the resistance to
      inotropes/vasopressors other than adrenaline is highly suggestive of an
      anaphylactoid reaction to pentastarch. The diagnostic value of serum tryptase may
      be compromised when blood samples are drawn too early.

PMID- 9579269
TI  - Continuous intra-arterial blood gas monitoring during oesophagectomy.
AB  - PURPOSE: To evaluate the clinical usefulness of the continuous intra-arterial
      blood gas (CIABG) monitoring system, Paratrend 7, during differential lung
      ventilation (DLV) in 12 patients undergoing oesophagectomy. METHODS: Anaesthesia
      was induced with propofol and was maintained with isoflurane, oxygen and air,
      supplemented by an epidural infusion of mepivacaine. Arterial samples for
      estimation of blood gases (ABG) were taken just before and 5, 10, 20, 30, 60, and
      90 min after the pleura was opened. The pH, PO2, and PCO2 values displayed by the
      CIABG monitor, which were recorded prior to the arterial blood sampling, were
      compared with the results of ABG analysis. RESULTS: Eighty-four blood samples
      were obtained and the ranges for the measured variables were PCO2 24.8-57.4 mmHg,
      PO2 47-449 mmHg, and pH 7.30-7.49. The correlation between CIABG and ABG
      measurements was strong and significant (r values: PCO2 0.80, PO2 0.93, pH 0.94).
      The overall bias +/- precision between the two methods was PCO2 0.9 +/- 3.1 mmHg,
      PO2 -1 +/- 40 mmHg, %PO2 0.8 +/- 21.6%, pH 0.00 +/- 0.02. For PO2 values < 150
      mmHg, the biases +/- precision were PO2 -5 +/- 17 mmHg, %PO2 -2.1 +/- 20.7%.
      CONCLUSION: The agreement between CIABG and ABG measurements was better for PCO2
      and pH than for PO2. Although the CIABG system is clinically useful for
      monitoring trends in blood gas changes, the accuracy of the PO2 value may be
      unacceptable during DLV because the error is theoretically < 34 mmHg with 95%
      reliability in the clinically important range of PO2, < 150 mmHg.

PMID- 9579270
TI  - Anaesthesia in Poland syndrome.
AB  - PURPOSE: To describe the anaesthetic management of a child with Poland syndrome
      for CT scan. CLINICAL FEATURES: An eight-month-old child presented with left
      upper limb hypoplasia and chest wall deformity with absence of ribs on the left
      side for CT scan of thorax. Pulsations of the heart could be seen along with
      paradoxical respiration over the defect. The trachea was intubated and the lungs
      ventilated manually to avoid inadequate ventilation and hypoxia. CONCLUSIONS: The
      unilateral absence of ribs leads to poor development of subatmospheric pressure
      in the thorax and paradoxical respiration, and may cause inadequate pulmonary
      ventilation and hypoxia. In the present case, positive pressure ventilation was
      chosen to maintain ventilation during the procedure.

PMID- 9579271
TI  - History of Canadian anaesthesia. Dr. Nelson Nix (b. 1915).

PMID- 9579272
TI  - Anaesthetic simulation.

PMID- 9579273
TI  - Metabolic events with spontaneous malignant hyperthermia.

PMID- 9579274
TI  - Metallic microparticles in the needle-through-needle technique.

PMID- 9579276
TI  - Intravenous obstruction and PCA machines.

PMID- 9579275
TI  - Persistent intraoperative myoclonus during propofol-fentanyl anaesthesia.

PMID- 9579278
TI  - A practical tracheal tube tie.

PMID- 9579277
TI  - Intrapleural placement of a nasogastric tube.

PMID- 9579279
TI  - From the bench to the bedside: the molecular management of cerebral ischemia.
AB  - Rapid and accurate management of a patient afflicted by cerebral ischemia is
      crucial for the development of a successful outcome. Yet, it is the understanding
      of the molecular and clinical presentation of cerebrovascular disease that
      enables the physician to diagnose and effectively treat cerebral ischemia.
      Neuronal degeneration can occur at several levels in the ischemic cascade. The
      free radical nitric oxide (NO) has been clearly linked to ischemic
      neurodegeneration in both animal models and cell culture systems, but the final
      cellular pathways that lead from the generation of NO to eventual neuronal death
      require further investigation. The protective mechanisms of the peptide growth
      factors basic fibroblast growth factor and epidermal growth factor appear to be
      linked to the signal transduction pathways of NO, programmed cell death, and
      protein kinase C. Active modulation of metabotropic glutamate receptor activity
      also can prevent neuronal injury at or below the level of NO generation. The
      molecular mechanisms that mediate the protective effects of the metabotropic
      glutamate receptors are dependent on the modulation of programmed cell death.
      Further investigation into the molecular signal transduction pathways that are
      responsible for ischemic neuronal injury will foster the development of
      efficacious and safe treatments for cerebral ischemia.

PMID- 9579280
TI  - A review of the randomized controlled trials of tacrine in the treatment of
      Alzheimer's disease: methodologic considerations.
AB  - This review examines the features of the 16 randomized controlled trials that
      have been published on the use of oral tacrine for treating probable Alzheimer's
      disease and explores the methodologic problems associated with these studies.
      Patient selection using the standard National Institute of Neurological and
      Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders
      Association (NINCDS/ADRDA) criteria is now a feature of all studies; however, the
      specificity of the diagnosis, the severity of the dementia, the heterogeneity of
      the dementia with respect to disease and patient genotype, and the health status
      of the patients all are factors that may affect responsiveness to therapy. Most
      studies use crossover designs; however, because of the progressive nature of the
      disease and the variability in the rate of decline, parallel group studies over a
      length of time sufficient to produce worsening in disease severity in a placebo
      group appear to be most suited to detecting clinically relevant therapeutic
      effects. The close relation between dose, efficacy, and serious adverse events
      has been a problem in the tacrine trials, since many studies, titrating to
      maximum tolerated doses, have used clinically ineffective doses. This problem can
      be circumvented by the use of fixed-dose regimens. Three broad classes of outcome
      measures have been used to assess treatment efficacy: 1) performance-based tests
      of cognitive function, 2) global impressions of change on the part of the
      clinician or care giver, and 3) functional measures of daily living. Including a
      limited number of each type of measure provides strong evidence of clinically
      relevant therapeutic benefit; however, more widely accepted and better validated
      instruments need to be developed for all three areas.

PMID- 9579281
TI  - Dietary treatment of destructive behavior associated with hyperphenylalaninemia.
AB  - Behavior disorders frequently are associated with mental retardation. The most
      common interventions involve psychotropics, behavior modification, or both.
      Etiologically based treatments, derived from an understanding of underlying
      disease pathogeneses, are infrequent. However, several genetic diseases are
      associated with elevated rates of destructive responding. The
      hyperphenylalaninemias provide an excellent model for alternative interventions
      that have clear biological plausibility. A literature review is undertaken that
      provides the biochemical rationale for treatment with a low-phenylalanine diet.
      Several phenylalanine dietary control studies designed to manage aberrant
      responding among patients with hyperphenylalaninemia are summarized. Together
      they provide strong evidence that dietary phenylalanine restriction is the
      treatment of choice among patients ranging from classic phenylketonuria to milder
      hyperphenylalaninemia. Corroborating evidence derived from phenylalanine loading,
      magnetic resonance imaging, and dietary amino acid supplementation studies is
      presented.

PMID- 9579282
TI  - Dose escalation safety and tolerance study of the competitive NMDA antagonist
      selfotel (CGS 19755) in neurosurgery patients.
AB  - Selfotel (CGS 19755), a competitive N-methyl-D-aspartate antagonist, is
      neuroprotective in experimental models of ischemic cerebral injury. We studied
      the safety and tolerability of a single intravenous dose (0.5 to 2.0 mg/kg) of
      selfotel in neurosurgery patients. Thirty-two neurosurgical patients undergoing
      intracranial surgery were given ascending doses of selfotel 2 to 14 h before
      surgery. Serum selfotel levels were measured over a period of 24 h. Cerebrospinal
      fluid (CSF) levels were measured 1.5 to 18 h after dosing. Frequent side effects
      included psychomimetic symptoms such as hallucinations, abnormal dreaming,
      agitation, and paranoia among 20 (66%) patients. Ataxia was seen among five (16%)
      and dizziness among eight (25%). Symptoms occurred 38 min to 40 h from
      administration and persisted 5 min to 4 days. Symptom severity worsened with
      increasing area under the curve measurements and doses above 1.0 mg/kg. All
      symptoms were reversible and easily treated with intravenous haloperidol. Modest
      elevations of hepatic enzymes were observed among four patients. No patient had
      severe adverse reactions. Maximum selfotel levels attained were 143 mumol (serum)
      and 4.76 mumol (CSF). Peak serum levels among six patients were within
      potentially neuroprotective ranges. CSF levels remained detectable up to 18 h
      after dosing. No obvious relationship was seen between CSF drug levels and
      symptoms. Selfotel in doses of 0.5 to 2.0 mg/kg can be administered safely to
      neurosurgical patients. Maximum serum levels attained were within the range shown
      to be neuroprotective in experimental studies. Side effects even at the highest
      levels are tolerable and reversible. Selfotel use in patients at risk for
      cerebral injury should be further explored.

PMID- 9579283
TI  - Antiparkinsonian effects of BAM-1110, a novel ergoline derivative, in MPTP
      treated cynomolgus monkeys.
AB  - BAM-1110 [(5R,8R,10R)-6-methyl-8-(1,2,4-triazol-l-ylmethyl) ergoline maleate] is
      a newly synthesized dopamine agonist that produces little anorexic side effects
      (nausea and vomiting). The current study examines the effects of BAM-1110 on
      parkinsonian symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      treated monkeys, an animal model of Parkinson's disease. First, a significant
      antiparkinsonian effect of apomorphine hydrochloride (0.3 mg/kg given
      subcutaneously) was confirmed in these animals. BAM-1110 (0.1, 0.3, and 1 mg/kg
      subcutaneously) relieved parkinsonian symptoms in a dose-dependent manner.
      Significant effects were observed at doses of 0.3 and 1 mg/kg and lasted for at
      least 3 h. BAM-1110, at a dose of 0.3 mg/kg that produced the submaximal
      antiparkinsonian effect, did not induce significant abnormal behaviors such as
      hyperactivity and stereotyped behaviors. Significant stereotyped behaviors were
      observed at 1 mg/kg of BAM-1110. Apomorphine induced hyperactive and stereotyped
      behaviors in parallel with its antiparkinsonian effect. BAM-1110 appears to be a
      potentially useful dopamine agonist to treat Parkinson's disease because of its
      relatively weak drug-induced hyperactive disturbances and anorexic side effects.

PMID- 9579284
TI  - Lamotrigine add-on therapy in focal epilepsy: electroencephalographic and
      neuropsychological evaluation.
AB  - The effect of lamotrigine (LTG) as add-on therapy on electroencephalogram (EEG)
      background activity was studied in 11 patients with refractory partial seizures
      with or without secondary generalization. The computerized EEG study was
      performed at rest with eyes closed (EC), during blocking reaction (BR), fixation
      (FIX), and mental arithmetic (MA) tasks. EEG spectral values were analyzed
      statistically using three-way ANOVA. The neuropsychological evaluation included a
      battery of six tests. Epileptic patients before LTG therapy, compared with
      control subjects, displayed at rest condition EEG changes consisting of higher
      delta and theta relative power coupled with lower alpha and beta power. During
      performance of attentive (BR) and cognitive (FIX) tasks, a decrease in alpha
      reactivity associated with a decrease of beta 1 and beta 2 power was found. The
      addition of LTG to previous therapy induced changes, although subtle, consisting
      of an increase in both alpha reactivity and beta power to attentive task.
      Neuropsychological evaluation did not evidence any impairment of cognitive
      functions. During LTG therapy, a decrease in seizure frequency occurred in 9 of
      the 11 patients whereas no changes were observed in the remaining 2. On the basis
      of these neurophysiologic and neuropsychological findings, LTG as add-on therapy
      does not seem to produce adverse side effects on mental activity; moreover, EEG
      data indicate a slight improvement in attentional processes.

PMID- 9579285
TI  - Intravenously administered acetylsalicylic acid in combination with low-dose
      heparin in acute ischemic stroke: a safety analysis.
AB  - Although therapy with acetylsalicylic acid (aspirin, ASA) is well established in
      secondary prevention of stroke, efficacy and side effects of this substance in
      acute stroke treatment are undetermined. ASA may be useful in acute cerebral
      ischemia because of its potential to prevent thrombus propagation and neuronal
      damage. A total of 268 patients with an acute cerebral ischemia, who were
      admitted to our stroke unit within 24 hours after stroke, were treated with
      intravenously administered ASA (0.5 g/day) in combination with low-dose heparin.
      The functional status of the patients was assessed after 1 month using the
      modified Rankin Scale. Eighteen (6.7%) patients died during the observation
      period. The functional status according to Rankin Scale was classified as stage 0
      in 76 (28.3%), 1 in 59 (22.0%), 2 in 39 (14.6%), 3 in 32 (12.3%), 4 in 36
      (13.4%), and 5 in 7 (2.6%) patients. A symptomatic secondary intracerebral
      hemorrhage was seen in one patient. Gastrointestinal symptoms were observed in 13
      (4.8%) patients, including five instances of gastrointestinal bleeding. Further
      complications were allergic reactions to aspirin (one) and hematuria (one).
      Recurrent cerebral ischemia occurred in nine (3.3%) patients (five with transient
      ischemic attack or minor stroke) during the observation period. We conclude that
      treatment of acute ischemic stroke with intravenously applied aspirin in
      combination with low-dose heparin is safe. Efficacy of this therapy should be
      elucidated in a controlled trial.

PMID- 9579286
TI  - Effects of valproate, phenobarbital, and carbamazepine on sex steroid setup in
      women with epilepsy.
AB  - Serum levels of sex-hormones, sex-hormone binding globulin, gonadotropin, and
      prolactin were evaluated during the follicular and the luteal phases in 65 women
      with epilepsy and in 20 healthy controls. Twenty-one patients were treated with
      sodium valproate (VPA), 21 with phenobarbital (PB), and 23 with carbamazepine
      (CBZ). VPA does not stimulate liver microsome enzymes, whereas PB and CBZ do.
      Patients on VPA therapy showed higher body weight and body mass index, but no
      significant differences in hirsutism score, or in ovary volume or polycystic
      ovary prevalence (at ultrasound examination). Estradiol levels were lower in all
      patient groups than in healthy controls in the follicular but not in the luteal
      phases. VPA affected luteal progesterone surge in 63.6% of cases. This effect was
      significantly lower in the CBZ and PB groups. Furthermore, increases in
      testosterone and delta 4-androstenedione levels and in free androgen index, along
      with a higher luteinizing hormone-follicle-stimulating hormone ratio in the
      luteal phase, were observed in women treated with VPA. Although sex-hormone
      binding globulin levels were higher in CBZ and PB than in VPA-treated patients,
      the differences were not significant because of the wide dispersion of the
      carrier protein levels. Inducer antiepileptic drugs decreased
      dehydroepiandrosterone sulfate levels, which remained unchanged during VPA
      treatment. No significant differences occurred in basal gonadotropin and
      prolactin levels.

PMID- 9579287
TI  - Pediatric sertraline overdose.
AB  - Sertraline (Zoloft) is a selective serotonin reuptake inhibitor that is commonly
      used in adults in the treatment of mood and anxiety disorders. Whereas it also is
      used to treat these illnesses in children, it is not currently approved by the
      Food and Drug Administration for use in this population. Sertraline use has been
      increasing secondary to its efficacy and its more tolerable side effect profile
      than the tricyclic antidepressants. It is also much safer in overdose than the
      tricyclic antidepressants. Although there have been numerous reports of
      sertraline overdose in adults, reports in the pediatric population are much less
      common. We review the literature regarding sertraline overdose in children,
      describe a case of sertraline ingestion in a 22-month-old infant, and discuss the
      treatment of such an overdose.

PMID- 9579288
TI  - Serum trace elements, glutathione, copper/zinc superoxide dismutase, and lipid
      peroxidation in epileptic patients with phenytoin or carbamazepine monotherapy.
AB  - Disturbance of metabolism of trace elements and antioxidants are investigated in
      epileptic patients with long-term therapy of anticonvulsants. One hundred and
      fifteen subjects including healthy controls, untreated epileptic patients, and
      phenytoin (PHT)- or carbamazepine (CBZ)-treated epileptic patients were recruited
      in this study. Serum malondialdehyde was measured as an index of extracellular
      lipid peroxidation. The levels of serum copper (S-Cu), serum zinc, copper/zinc
      superoxide dismutase (CuZn-SOD), and reduced glutathione in the serum were
      monitored simultaneously. The results showed that malondialdehyde, S-Cu, and CuZn
      SOD levels in the serum all were significantly increased, but the glutathione
      level was significantly decreased, in all the epileptic patients with PHT
      monotherapy compared with those of the controls. However, no significant
      differences of these parameters in the epileptic patients with CBZ monotherapy
      were found except for a mild elevation of the activity of serum CuZn-SOD. We
      conclude that compared with PHT monotherapy, the CBZ monotherapy induced less
      disturbance in trace element metabolism, antioxidants, and lipid peroxidation in
      the serum of epileptic patients.

PMID- 9579289
TI  - Lamotrigine in the treatment of resistant bipolar disorder.
AB  - Antiepileptic drugs, such as carbamazepine and sodium valproate, are integral to
      psychopharmacologic therapy over the last decades. Lamotrigine is a new
      antiepileptic drug that acts on amino acid neurotransmitters/neuromodulators,
      most prominently, glutamine, which has been reported to have potential mood
      stabilizing effects. The reports on this effect are limited and sparse, and
      systematic investigations have not been published. Here we present two clinical
      cases representing atypical patient groups in which lamotrigine was successfully
      used as an add-on therapy for resistant bipolar depression.

PMID- 9579290
TI  - Marked improvement of tardive dystonia after replacing haloperidol with
      risperidone in a schizophrenic patient.
AB  - We report on a schizophrenic patient whose tardive dystonia, delusions, and
      auditory hallucinations showed remarkable concurrent improvement after replacing
      haloperidol with risperidone. The present finding suggests that the 5
      hydroxytryptamine-2 (5-HT2) antagonistic action of risperidone has brought about
      the improvement in tardive dystonia. The 5-HT2 antagonistic action of
      risperidone, in addition to its dopamine antagonistic action, may have also
      lessened psychotic symptoms in the current case.

PMID- 9579291
TI  - Current status of NMDA antagonist interventions in the treatment of nonketotic
      hyperglycinemia.
AB  - Impairment of the catabolism of glycine caused by "failure" of the glycine
      cleavage enzyme complex results in an inability to oxidatively decarboxylate this
      amino acid. As a result of this inability, the alpha carbon of glycine does not
      enter the one-carbon pool, leading to its reduction or depletion, and toxic
      accumulation of this amino acid neurotransmitter occurs. Strategies for the
      treatment of the clinical condition known as nonketotic hyperglycinemia, an
      autosomal recessive disorder associated with absent or diminished glycine
      cleavage enzyme activity, include reduction of the glycine burden, replenishment
      of the one-carbon pool, and antagonism of the neurotransmitter effects of
      glycine. Until recently, antagonism focused on interference with the glycine
      associated chloride ionophore that is enriched in the brain stem and spinal cord,
      using strychnine as a specific intervention. However, the recent recognition of a
      "strychnine-insensitive" binding site for glycine on the N-methyl-D-aspartic acid
      (NMDA) receptor complex, a glutamate-gated cationic channel, has led to some
      newer approaches. Also, the recognition of milder, atypical variants of classic
      nonketotic hyperglycinemia has stimulated efforts to evaluate the therapeutic
      efficacy of these strategies to antagonize the NMDA receptor complex.

PMID- 9579292
TI  - Pilot investigation of thyrotropin-releasing hormone-induced thyrotropin and
      prolactin release in anxious patients treated with diazepam.
AB  - Benzodiazepines have been reported to inhibit thyrotropin (TSH) and prolactin
      (PRL) secretion in response to stressful and pharmacologic stimuli in
      experimental animals. The current study investigates basal and thyrotropin
      releasing hormone (TRH)-stimulated TSH and PRL release in anxious patients
      treated with diazepam. Six hospitalized patients having generalized anxiety or
      adjustment disorder with anxious mood (DSM III-R criteria) were treated during 1
      week with diazepam (mean daily dose 33.3 mg). TRH testing was performed
      comparatively before and after 7 days of diazepam administration (with 250
      micrograms protirelin and blood sampling at 15-min intervals over 60 min). Steady
      state plasma levels of diazepam and its metabolite nordazepam (desmethyldiazepam)
      were determined by high-performance liquid chromatography. After 7 days of
      diazepam treatment, basal plasma levels of TSH and PRL were not affected compared
      with pretreatment values. Similarly, the time-course of TRH-induced TSH release
      was not modified by the treatment. By contrast, there was a trend to decrease in
      the TRH-induced PRL release, and the decrease in the PRL response to TRH on day 7
      was significantly correlated with plasma nordazepam concentrations (rs = 0.943, p
      = 0.02). These preliminary results suggest that benzodiazepines, at therapeutic
      doses for the treatment of anxiety, may alter TRH-induced PRL release in humans.

PMID- 9579294
TI  - The therapeutic effect of moclobemide, a reversible selective monoamine oxidase A
      inhibitor, in Parkinson's disease.
AB  - In this open study, the therapeutic effect of moclobemide, a reversible selective
      monoamine oxidase A inhibitor, was tested in 20 patients with Parkinson's disease
      who developed levodopa-induced motor response complications. Moclobemide as
      adjunct therapy reduced "off" time duration for 27%, without an overall motor and
      functional improvement during their "on" periods. Since it was well tolerated,
      moclobemide may be specially indicated in elderly or depressed fluctuating
      parkinsonian patients.

PMID- 9579293
TI  - Pharmacodynamics of levodopa coadministered with apomorphine in parkinsonian
      patients with end-of-dose motor fluctuations.
AB  - The modification of the pharmacodynamic response to a single oral dose of
      levodopa/benserazide by the coadministration of the dopamine agonist apomorphine
      was investigated in parkinsonian patients with end-of-dose motor fluctuations.
      The relation between levodopa plasma concentrations and motor response was
      examined in a double-blind, randomized, crossover design in 10 patients with
      idiopathic Parkinson's disease with end-of-dose motor fluctuations. Oral single
      dose challenges with 100 mg of levodopa/25 mg of benserazide were carried out
      twice in each patient, under coadministration with apomorphine (1 mg/h) or 0.9%
      saline (placebo) subcutaneously. The sum scores (sigma score) of the Columbia
      University Rating Scale (CURS) were used as effect parameters for pharmacodynamic
      assessment. A sigmoidal Emax model was fitted to the data using a semiparametric
      pharmacokinetic-pharmacodynamic approach. Levodopa pharmacokinetics were not
      significantly modified by the coadministration of apomorphine. The area under the
      curve was 1599 +/- 615 ng.ml-1 h. (levodopa + saline) and 1821 +/- 625 ng.ml-1.h
      (levodopa + apomorphine). Cmax was 1094 +/- 476 ng.ml-1 (levodopa + saline) and
      1129 +/- 435 ng.ml-1 (levodopa + apomorphine). Under both experimental regimens,
      the maximum clinical response to levodopa (Emax) yielded a decrease in the CURS
      sigma rating of about 20 score points. Estimates of the EC50 of levodopa
      decreased significantly from 430 +/- 163 ng.ml-1 (levodopa + saline) to 315 +/-
      123 ng+ml-1 (levodopa + apomorphine) (95% confidence interval [CI] 0.51 -0.98,
      point estimator 0.75). The mean duration of the motor response rose from 1.9 +/-
      0.5 h (levodopa + saline) to 3.0 +/- 0.9 h (levodopa + apomorphine (95% CI 1.23
      to 2.06, point estimator 1.60). Thus, a reduction of the threshold levels for
      levodopa (EC50) was accompanied by approximately 50% gain in on-phase duration,
      but not in an increased magnitude of the motor response (Emax).

PMID- 9579295
TI  - Emergence of obsessive--compulsive symptoms and tics during clozapine withdrawal.
AB  - Treatment with clozapine may be associated with the appearance of obsessive
      compulsive (OC) symptoms in up to 10% of schizophrenic patients. We present the
      first report of the emergence of de novo OC symptoms during clozapine withdrawal
      in two schizophrenic patients, associated in one with Tourette's syndrome-like
      tics. Resumption of clozapine led to the complete disappearance of the OC
      symptoms and a substantial alleviation of the tics. It is suggested that an
      imbalance between the dopamine and serotonin systems may account for this
      complication.

PMID- 9579298
TI  - Gender differences in Parkinson's disease.
AB  - We examined data from 630 patients entered into the University of Kansas Medical
      Center's Parkinson's Disease (PD) Registry to determine if gender differences
      exist in terms of both cognitive and motor symptoms of PD. An analysis of the
      Mini-Mental State Examination scores indicated slightly higher scores for women
      relative to men. Although women had significantly better scores than did men on
      the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS), they
      had a significantly greater prevalence of dyskinesias compared with men. These
      motor differences were significant only in patients with PD of greater than 5
      years duration. There were no gender differences for age of diagnosis, Hoehn and
      Yahr Staging, Schwab and England Scale, or the mentation and activities of daily
      living sections of the UPDRS. We conclude that as PD progresses, gender
      differences emerge, with men exhibiting more severe parkinsonian motor features
      and women experiencing more levodopa-induced dyskinesia.

PMID- 9579297
TI  - Attentional deficits in Parkinson's disease: partial reversibility with
      naphtoxazine (SDZ NVI-085), a selective noradrenergic alpha 1 agonist.
AB  - Several authors have suggested that catecholamine depletion may affect
      attentional processes in human subjects and could be implicated in the frontal
      lobe syndrome that has been described in Parkinson's disease (PD). The present
      study reports the effects of a placebo and naphtoxazine (SDZ-NVI-085), a
      selective noradrenergic alpha 1 agonist. These substances were administered to
      nine parkinsonian patients who were assessed on measures of attention, including
      neuropsychological tests and evoked potentials. The results indicate that
      naphtoxazine may improve performance on some tests of "frontal functions,"
      including the Stroop and the Odd-Man-Out tests, which have been previously found
      to be affected in PD. However, the results of some other neuropsychological tests
      of frontal function were not affected by naphtoxazine. Specific evoked potentials
      such as the Nd1 and Nd2 curves--which are thought to reflect attentional
      processes and which have been found to be affected in PD--were improved by
      naphtoxazine. Finally, naphtoxazine reduced the percentage of errors and restored
      the lateralization of N100 during the Shifting Reaction Time Task, suggesting
      that this substance may act on the processes underlying the shifting deficit in
      these patients. The results are discussed in terms of the specific cognitive
      processes that may be affected by naphtoxazine and in terms of the role of the
      noradrenaline in attentional deficits found in PD.

PMID- 9579299
TI  - The relationship between phenytoin pharmacokinetics and the CYP2C19 genotype in
      Japanese epileptic patients.
AB  - The relationship between the phenytoin pharmacokinetics, expressed by the mean of
      the Michaelis-Menten equation and the CYP2C19 genotype was investigated in 16
      Japanese epileptic patients treated with phenytoin. Between genetically (S)
      mephenytoin poor and extensive metabolizers, there were no differences in the
      Michaelis-Menten parameters. But divided into genotype groups, Vmax values were
      3.9 +/- 0.4, 5.3 +/- 0.7, and 5.7 +/- 1.4 mg/kg/day for the patients with the m2
      allele, with the m1 allele, and with neither the m1 or m2 allele, respectively.
      In the patients with the m2 allele of CYP2C19, the Vmax value was significantly
      lower than in those without the m2 allele. It is possible that the m2 allele of
      CYP2C19 may be one of the factors of slow phenytoin metabolism, and its frequency
      may underlie the ethnic difference in phenytoin metabolism between Japanese and
      white individuals.

PMID- 9579296
TI  - A placebo-controlled evaluation of ropinirole, a novel D2 agonist, as sole
      dopaminergic therapy in Parkinson's disease.
AB  - The efficacy and safety of ropinirole, a novel nonergot dopamine D2-like receptor
      agonist, was assessed as monotherapy for the treatment of patients with early
      stage Parkinson's disease. In this double-blind, multicenter trial, patients were
      randomly allocated in a ratio of 2:1 to receive, over a 12-week period, either
      ropinirole or placebo. Clinical status was assessed using the Unified Parkinson's
      Disease Rating Scale (UP-DRS), Clinician's Global Evaluation (CGE), and a finger
      tapping score. In all, 41 patients received ropinirole and 22 received placebo.
      The end-point analysis, on an intention-to-treat basis, revealed a significant
      difference (p = 0.018) in improvement in UP-DRS motor score from baseline between
      treatment groups (ropinirole, 43.4%; and placebo, 21.0%). Other parameters,
      including the number of responders and improvement in CGE, showed similar
      results. Three patients in the ropinirole group and one patient in the placebo
      group discontinued the study because of adverse events. There was no significant
      difference between the treatment groups in the overall incidence of adverse
      events. Although the dopaminergic side effects were reported significantly more
      frequently in the ropinirole group than in the placebo group (dizziness, p =
      0.0326; nausea, p = 0.001; and somnolence, p = 0.005), none necessitated study
      withdrawal. There was no evidence of any chronic effect of the study medication
      on vital signs. In conclusion, ropinirole is a safe and well-tolerated drug and,
      as monotherapy, provided significant therapeutic benefit compared with placebo to
      patients in the early stages of Parkinson's disease.

PMID- 9579300
TI  - Interaction of modafinil and clomipramine as comedication in a narcoleptic
      patient.
AB  - Modafinil is a psychostimulant compound that is just now becoming available in
      many countries for treatment of narcoleptic and hypersomnic patients. Whereas
      sleep attacks and drowsiness can be effectively improved, the drug does not
      sufficiently reduce cataplectic seizures. It therefore is often used in
      combination with tricyclic antidepressant medication, although little is known
      about the possible interactions. This case report describes a narcoleptic patient
      chronically treated with clomipramine who started receiving modafinil. The blood
      concentrations of clomipramine and its metabolite showed a significant dose
      dependent and reversible increase under modafinil. Since the patient was
      genotypically and phenotypically a cytochrome P450 2D6 poor metabolizer, the
      authors attribute the relevant pharmacokinetic interaction to another
      clomipramine-metabolizing enzyme.

PMID- 9579301
TI  - Increased ocular pressure in two patients with narrow angle glaucoma treated with
      venlafaxine.
AB  - Venlafaxine blocks the specific monoamine transporters and is devoid of
      significant action on muscarinic cholinergic receptors. To our knowledge, no
      cases of glaucoma have been reported so far. Because pain perception involves
      both serotonergic and noradrenergic mechanisms, venlafaxine also may be useful in
      neuropathic pain therapy. We report on two patients with narrow angle glaucoma
      affected by chronic pain. When venlafaxine treatment was begun, their ocular
      pressure was steadily around 17-18 mmHg. Venlafaxine was chosen (daily dose 75
      mg) because this drug is claimed not to bind on muscarinic cholinergic receptors.
      However, 4 days later the ocular pressure of the first patient increased to 22
      mmHg, which led to suspension of the drug. The ocular pressure of the second
      patient was 18.5 mmHg after a week, 21 mmHg after 2 weeks, and 23 mmHg after 16
      days. One week after suspension, ocular pressure of the patients was 17 and 18
      mmHg, respectively. Possible explanations of this ocular effect are offered:
      pharmacokinetic interference on the drugs used in glaucoma treatment, in vivo
      action on the muscarinic receptor, indirect effect via dopaminergic receptors, or
      direct effect on the ocular sympathetic postganglionic neurones. In any case,
      from a clinical viewpoint, caution should be used when giving venlafaxine to
      patients with narrow-angle glaucoma, and ocular pressure must be monitored.

PMID- 9579302
TI  - Clozapine for the treatment of agitated-depressed patients with cognitive
      impairment: a report of three cases.
AB  - Clozapine, an atypical antipsychotic, is mainly approved for the treatment of
      resistant schizophrenia. However, a substantial body of evidence suggests that it
      might be useful in other psychiatric indications, such as treatment-resistant
      depression, Parkinson's disease, and dementia. In this report we present the
      cases of three patients hospitalized at the psychiatric division of the Sheba
      Medical Center, diagnosed with major depressive disorder with cognitive
      impairment, whose presenting symptom was agitation. These patients were
      nonresponders to various treatment modalities. However, treatment with clozapine
      brought about a favorable response.

PMID- 9579303
TI  - Changes in the motor response to acute L-dopa challenge after unilateral
      microelectrode-guided posteroventral pallidotomy.
AB  - To determine the effect of unilateral posteroventral pallidotomy (PVP) on latency
      and duration of response to L-dopa ipsilateral and contralateral to the side of
      the lesion, six severe fluctuating Hoehn-Yahr IV patients with Parkinson's
      disease were evaluated 2 days before and after unilateral PVP. After an overnight
      drug holiday in a fasting state, patients were challenged with a single dose of
      200/50 mg of L-dopa/ carbidopa. Sequential tapping tests every 5 minutes in both
      hands were used to measure changes in motor status. Duration of L-dopa effect was
      significantly longer after PVP (p < 0.03). Mean latency of the effect improved by
      50% without reaching statistical significance. Despite a clear, asymmetric
      improvement of cardinal Parkinson's disease symptoms after unilateral PVP,
      changes in the dose-response L-dopa profile occurred symmetrically, suggesting
      that mechanisms underlying the two effects are distinct.

PMID- 9579304
TI  - Treatment of clozapine induced hypertension and possible mechanisms.

PMID- 9579305
TI  - Cornelius H. Vanderwolf Festschrift.

PMID- 9579306
TI  - Brain, behavior, and mind: what do we know and what can we know?
AB  - I have attempted a comprehensive review of psychological and neuroscientific
      findings relevant to the problem of mind in relation to the brain and behavior.
      The following conclusions are suggested: (a) current discussions of the mind
      often make implicit assumptions derived from the theories of Aristotle and
      Descartes while ignoring more recent scientific evidence; (b) psychological
      studies indicate that humans are directly aware of the external world and of
      their own bodies but of little else. Descartes' assumption that one has direct
      access to one's own thoughts appears to be an error; (c) there are no clear
      objective criteria for assessing the existence of subjective awareness in others.
      This problem is particularly acute in the cases of non-human animals and humans
      with impaired brain function; (d) the theory that the conventional subdivisions
      of the mind, such as emotion or cognition, reflect natural subdivisions of brain
      function is largely false; and (e) the main scientific challenge confronting
      neuroscience is not explaining the mind but rather achieving an understanding of
      how neural activity generates behavior.

PMID- 9579307
TI  - Age, experience and the changing brain.
AB  - In this review, various aspects of how environmental experience effects the
      structure of the cortex at different times in the age of the animal are
      summarized. The interactions of brain injury and sex on the age-dependent plastic
      changes in the cortex are also considered. Finally, we have attempted to reach
      some general conclusions that describe the effects of age, experience, sex, and
      injury on the cortex.

PMID- 9579308
TI  - Frames of reference for perception and action in the human visual system.
AB  - A growing body of evidence demonstrates that vision for perception and vision for
      action are mediated by separate neural mechanisms. After briefly reviewing the
      neuropsychological evidence for this division of labor in the human visual
      system, we explore the evidence for a dissociation between perception and action
      in neurologically intact individuals. A number of studies have shown that unseen
      visual events can sometimes elicit movements of the hand and limb, despite the
      fact that subjects have no visual phenomenology of those events. Other work has
      shown that perceptual judgements about the location and size of objects can be
      quite different from the scaling of skilled actions directed at those objects.
      For example, size-contrast illusions, such as the Ebbinghaus illusion, have been
      shown to have little effect on the scaling of the grasp. Similar dissociations
      have been demonstrated in other studies in which psychophysical judgements about
      the dimensions of objects in the far peripheral field bear little relation to the
      calibration of grasping movements directed at those objects. Together with the
      neuropsychological work (and neurophysiological studies in the monkey), these
      findings provide compelling evidence for the operation of separate visual
      mechanisms in everyday life. In other words, what we think we see is not always
      what guides our actions.

PMID- 9579309
TI  - Comparative perspectives on multiple cortical visual systems.
AB  - This paper argues that any effort to extend theories of cortical visual systems
      based on primates to other orders, such as Rodentia, must take into account
      fundamental differences in visual system properties, such as retinal
      organization. Some examples are given of the effects of these differences,
      describing several studies using gerbils in which problems in object recognition
      appear to be solved using unique methods based on navigational information. I
      conclude by suggesting that closer consideration of comparative issues in visual
      cortical processing might lead to new insights regarding the evolutionary origins
      of object recognition as it is understood in humans and other primates, and I
      suggest that these evolutionary antecedents might help to explain the apparent
      linkage in humans between object recognition and movement.

PMID- 9579310
TI  - Testing the NMDA, long-term potentiation, and cholinergic hypotheses of spatial
      learning.
AB  - The problems and issues associated with the use of pharmacological antagonists in
      studies on learning and memory are considered in a review of the role of N-methyl
      D-aspartate (NMDA) receptors, NMDA receptor-mediated long-term potentiation
      (LTP), and muscarinic receptors in spatial learning in the water maze. The
      evidence indicates that neither NMDA nor muscarinic receptors, nor NMDA receptor
      mediated LTP, are required for spatial learning, although they might normally
      contribute to it. Detailed behavioral analyses have indicated that the water maze
      task is more complex than generally has been appreciated, and has a number of
      dissociable components. Naive rats trained under NMDA or muscarinic antagonism
      display sensorimotor disturbances that interfere with their ability to acquire
      the task. Rats made familiar with the general requirements of the task can learn
      the location of a hidden platform readily under NMDA or muscarinic antagonism.
      The ability of a rat to acquire the water maze task depends on its ability to
      apply instinctive behaviors to performance of the task in an adaptive manner. The
      instinctive behaviors undergo modification as the rat learns the general
      strategies required in the task. The evidence suggests that at least some of the
      plastic changes involved in acquiring the task occur in existing neural circuits
      situated in widespread areas of the brain, including sensory and motor structures
      in the cortex and elsewhere, and are therefore difficult to distinguish from
      existing sensorimotor mechanisms. More generally, the findings indicate the
      difficulty of inferring the occurrence or nonoccurrence of learning from
      behavior, and the difficulty of causally linking the action of particular
      receptor populations with the formation of specific memories.

PMID- 9579311
TI  - Post-activation potentiation in the neocortex of awake freely moving rats.
AB  - The search for the cellular processes that underlie information storage within
      neuronal systems lead to the development of two models of post-activation
      potentiation, long-term potentiation (LTP) and kindling. Both models give rise to
      a long-lasting increase in synaptic strength and altered unit discharge patterns.
      The present paper reviews synaptic plasticity in the neocortex of awake freely
      moving rats following both single and multiple sessions of activation with high
      frequency, tetanic electrical stimulation. The phenomenology of neocortical post
      activation potentiation and some possible underlying mechanisms are discussed. We
      speculate that the functional significance of potentiated responses may reflect a
      reorganization of the neocortex in a manner similar to those that create and
      define receptive fields.

PMID- 9579312
TI  - Place learning in hippocampal rats and the path integration hypothesis.
AB  - Although two decades of research suggests that the hippocampus plays a special
      role in place learning, the present paper describes a series of studies using
      swimming pool spatial tasks that show that hippocampal rats have considerable
      place learning ability, which includes the abilities of finding, remembering, and
      searching for places. The same studies also show that when environmental cues are
      uninformative, as is the case early in original learning and again in reversal
      learning, hippocampal rats are impaired. Since control rats quickly resolve
      spatial ambiguity in these situations, it is argued that they must have a system
      with which they can calibrate spatial cues. The discussion considers the
      possibility that they use dead reckoning with path integration, a spatial
      strategy that provides guidance based on cues generated by a point of reference
      and subsequent self-movement and not the cues in the environment through which
      they are moving. With path integration an animal can monitor its location and at
      the same time attach spatial meaning to cues that it encounters. An ability to
      recalibrate external cues may provide the tuning that allows control rats to
      quickly acquire place responses while hippocampal rats are constrained by the
      processes of associative learning.

PMID- 9579313
TI  - Hippocampal formation theta activity and movement selection.
AB  - Hippocampal theta activity results from activation in the ascending synchronizing
      system. It occurs during sensory/signal processing prior to and coincident with
      voluntary movements in mammals. The experiments summarized here suggest that it
      is involved in the organization of motor behaviour. (1) Procaine (a local
      anaesthetic) infused into the medial septum (MS) abolishes hippocampal theta
      activity and running behaviour elicited by electrical posterior hypothalamic (PH)
      stimulation. This indicates that movement elicited by PH stimulation, is
      dependent on ascending hypothalamo-septal circuitry. (2) Theta can also be
      recorded in immobile rats prior to the initiation of lateral dodging movements
      they make in response to conspecific rats attempting to steal their food.
      Following infusion of atropine into the MS, theta recorded during immobility is
      abolished and the rats are severely impaired at initiating movements in defence
      of their food. It is suggested that atropine-sensitive theta is involved in the
      initiation of movements made by rats in response to sensory stimuli. (3) Rats
      with fimbria-fornix transections were also less likely to engage in lateral
      dodging movements in defence of their food, were hyperactive, less thigmotaxic,
      and defecated more often, compared to control animals. Depth profile analysis of
      hippocampal field activity in lesioned animals revealed an absence of theta
      during electrical or chemical pons stimulation. These findings provide evidence
      that these neural systems are involved in signal processing relevant to movements
      underlying adaptive behaviour.

PMID- 9579314
TI  - Relationships between hippocampal activity and breathing patterns.
AB  - Single cell discharge, EEG activity, and optical changes accompanying alterations
      in breathing patterns, as well as the knowledge that respiratory musculature is
      heavily involved in movement and other behavioral acts, implicate hippocampal
      regions in some aspects of breathing control. The control is unlikely to reside
      in oscillatory breathing movements, because such patterns emerge in preparations
      retaining only the medulla (and perhaps only the spinal cord). However, momentary
      changes in breathing patterns induced by affect, startle, whole-body movement
      changes, or compensatory ventilatory changes mediated by rostral brain regions
      likely depend on hippocampal action in aspects of control. Hippocampal activity
      was enhanced prior to sighs, and this enhancement was accompanied by increased
      slow theta activity. Theta frequency increased during apnea, prior to return of
      breathing. Consideration of hippocampal contributions to breathing control should
      be viewed in the context that significant interactions exist between blood
      pressure changes and ventilation, and that modest breathing challenges, such as
      exposure to hypercapnia or to increased resistive loads, bring into action a vast
      array of brain regions involving nearly every level of the neuraxis.

PMID- 9579315
TI  - Hippocampal theta: a sensory-inhibition theory of function.
AB  - The most prominent electrical signal which can be recorded from the hippocampus
      is called theta rhythm. Over the past 30 years there have been numerous attempts
      to relate this waveform to behavior. Theta has been associated with arousal,
      learning memory, attention, and most recently motor movement. While the
      relationship between one type of theta and certain kinds of movement is well
      established, a second type of theta shows no such relationship. In the present
      paper it is argued that the most parsimonious hypothesis relating theta to
      behavior is not the motor programming theory but a sensory-inhibition model. In
      this model theta is regarded as representative of general inhibition of systems
      not being used during motor behavior or alert immobility.

PMID- 9579316
TI  - Involvement of direct and indirect pathways in electrocorticographic activation.
AB  - Recent evidence indicates that neocortical electrocorticographic (ECoG)
      activation depends critically on cholinergic (ACh) inputs from the basal
      forebrain and serotonergic (5-hydroxytryptamine, 5-HT) inputs from the midbrain
      raphe to the neocortex. It appears that ACh and 5-HT block synchronized ECoG
      activity and induce cortical activation by a direct, local action in the
      neocortex that is not mediated by secondary systems. Concurrent blockade of
      cholinergic and serotonergic inputs to the cortex abolishes all ECoG activation,
      suggesting that: (a) together, ACh and 5-HT are essential for cortical activation
      to occur; and (b) other systems cannot maintain cortical activation in the
      absence of the cholinergic and serotonergic inputs. Nevertheless, additional
      neural systems (amygdala, locus coeruleus-noradrenaline (-NA), superior
      colliculus, orbitofrontal cortex, dopamine, histamine, glutamate) also modulate
      the ECoG and can produce cortical activation. In contrast to ACh and 5-HT,
      however, none of these systems are essential for the maintenance of cortical
      activation. Further, rather than producing activation via direct inputs to the
      neocortex, these systems appear to produce cortical activation by stimulating the
      cholinergic or serotonergic inputs to cortex. Thus, neocortical activation is
      maintained by multiple, parallel systems; cholinergic and serotonergic pathways
      are essential for activation and produce activation directly and locally in the
      neocortex, whereas additional pathways are not essential and contribute to
      activation indirectly by acting through these two direct activating inputs to the
      cortex.

PMID- 9579317
TI  - Anatomical, electrophysiological and pharmacological studies of ascending
      brainstem hippocampal synchronizing pathways.
AB  - The present review has provided evidence that very potent ascending brainstem
      hippocampal synchronizing pathways originate in the rostral pons region (RPO and
      PPT), and ascend to and synapse with several midline caudal diencephalic nuclei
      (posterior hypothalamic and supramammillary) which send projections to the medial
      septal region (MS/vDBB). The medial septal region in turn is a critical nodal
      point, sending projections to limbic structures such as the hippocampal
      formation, cingulate cortex, and entorhinal cortex. The pontine and diencephalic
      nuclei appear to play a critical role in determining the translation of
      increasing levels of activation into moment to moment changes in the frequency of
      hippocampal theta field and theta-related cellular discharges, relayed to the
      MS/vDBB nuclei. The MS/vDBB nuclei appear to play a critical role in translating
      increasing levels of ascending synchronizing activation into moment to moment
      changes in the amplitude of hippocampal theta field activity and the accompanying
      rate and pattern of phasic theta-ON cells. The MS/vDBB carries out this role
      through a balance of activity in the septohippocampal cholinergic and GABA-ergic
      projections. Cholinergic projections provide the afferent excitatory drive for
      hippocampal theta-ON cells and the GABA-ergic projections act to reduce the
      overall level of inhibition by inhibiting hippocampal GABA-ergic interneurons
      (theta-OFF cells). Both activities must be present for the generation of
      hippocampal theta and theta-related cellular activities. The balance between the
      cholinergic and GABA-ergic projections may determine whether hippocampal
      synchrony (theta) or asynchrony (LIA, large amplitude irregular activity) occurs.
      These same ascending pathways influence the electrophysiological and
      pharmacological properties of the neocortex as well. The functional significance
      of the ascending brainstem synchronizing pathways is the generalized regulation
      of activities in these cortical structures as they relate to sensorimotor
      behavior.

PMID- 9579318
TI  - Generation of theta and gamma rhythms in the hippocampus.
AB  - In the behaving rat, theta rhythm was dominant during walking and rapid-eye
      movement sleep, while irregular slow activity predominated during immobility and
      slow-wave sleep. Oscillatory evoked potentials of 20-50 Hz and spontaneous fast
      (gamma) waves were more prominent during theta compared with non-theta behaviors.
      The oscillations were simulated by a systems model with recurrent inhibition. The
      model also predicts a behaviorally dependent inhibition, which was confirmed
      experimentally using paired-pulse responses. Paired-pulse facilitation (PPF) of
      the population spikes in CA1 was larger during walking than immobility, mostly
      mediated by a cholinergic input. Spike responses in vitro were characterized by a
      relative lack of inhibition or disinhibition compared with the behaving rat. The
      two-input, two-dipole model of the theta rhythm in CA1 is reviewed. Afferents to
      the CA1 pyramidal cells are assumed to be rhythmic and consist of atropine
      sensitive and atropine-resistant inputs driving the somata and distal dendrites,
      respectively. The atropine-sensitive theta rhythm was mainly caused by a series
      of Cl- mediated inhibitory postsynaptic potentials (IPSPs) on pyramidal cells. It
      is suggested that previous claims of the participation of excitatory postsynaptic
      potentials (EPSPs) and not IPSPs in the intracellular recordings in vivo were
      flawed. Single cell recordings in vitro suggested that intrinsic voltage
      dependent membrane potential oscillations modulate the response to a theta
      frequency driving. Membrane potentials of pyramidal cells in vitro showed
      resonance in the theta frequency range.

PMID- 9579319
TI  - Frequency modulation of hippocampal theta by the supramammillary nucleus, and
      other hypothalamo-hippocampal interactions: mechanisms and functional
      implications.
AB  - In this paper it is argued that theta-range hippocampal EEG activity, and in
      particular the specific frequency at which it occurs, is critical to hippocampal
      function. Results of the reviewed studies suggest that in particular
      circumstances (in the urethane anaesthetized animal and possibly during
      particular behavioral states), the frequency of hippocampal theta is primarily
      determined in the supramammillary nucleus (SuM). Rhythmic theta-frequency
      neuronal activity in the SuM is relayed to, and determines the frequency of theta
      activity in, the septum (and hence the hippocampus). It is also suggested that in
      general (e.g., freely moving, as opposed to anaesthetized animals, and in all but
      some specific behavioral states), other ascending pathways and mechanisms in
      addition to those from SuM are probably also involved in the modulation of theta
      frequency. The posterior hypothalamic nucleus (PH) probably acts in synergy with
      the SuM, but it is principally involved in the release and amplitude modulation
      of theta. Although descending input from the septo-hippocampal system to PH and
      SuM is not required for theta-related neuronal activity in these structures, we
      provide evidence for descending, rate-limiting influences from the septo
      hippocampal system to both PH and SuM during theta. These descending systems are
      likely involved in the suppression of theta during non-theta (i.e., sharp-wave)
      hippocampal EEG. In contrast to the SuM and PH, theta-related neuronal activity
      in the medial mammillary nucleus (MM) is dependent on theta-frequency activity
      in, and descending from, the septo-hippocampal system. The MM it is argued, is
      involved in relaying theta-frequency activity around the limbic circuitry. A role
      for this re-entrant process is suggested.

PMID- 9579320
TI  - Operational dynamics in the hippocampal-entorhinal axis.
AB  - How do ensembles of neurons distributed across the hippocampal and entorhinal
      cortices effectively interact? In the awake-behaving rat, specific subpopulations
      of hippocampal and entorhinal neurons become entrained into two prominent fast
      frequency rhythms (gamma [40-100 Hz], and 200 Hz). These fast rhythms are coupled
      to slower synchronizing potentials (theta and sharp wave, respectively), are
      correlated to macroscopic behavioral states, and to some extent are anatomically
      distinct. These population dynamics allow distributed populations of neurons
      across the hippocampal and entorhinal cortices to discharge together in time on
      the order of tens of milliseconds, and thus allow interconnected domains of a
      distributed neural network to become transiently entraining into synchronized,
      fast-frequency, population ensembles. We believe that these transient population
      dynamics allow interconnected domains to "effectively communicate" and modify
      their synaptic connectivity.

PMID- 9579321
TI  - Theta-like activity in the limbic cortex in vitro.
AB  - The generation of EEG theta rhythm in the mammalian limbic cortex is a prime
      example of rhythmic activity that involves central mechanisms of oscillations and
      synchrony. This EEG pattern has been extensively studied since 1938, when Jung
      and Kornmuller (28) (Eine methodik der ableitung lokalisierter potential
      schwankingen aus subcorticalen hirnyebieten, Arch. Psychiat. Neruenkr. 109 (1938)
      1-30) demonstrated the first theta recordings in the hippocampal formation of
      rabbits. In 1986 we demonstrated for the first time that bath perfusion of
      hippocampal slices with the cholinergic agonist, carbachol, resulted in theta
      like oscillations. Since this initial demonstration of in vitro theta-like
      activity, we have carried out a number of experiments in an attempt to answer the
      following question: what are the similarities between cholinergic-induced in
      vitro theta-like activity and theta rhythm which naturally occurs in the in vivo
      preparation. Thus far, our studies have provided strong evidence that theta-like
      activity recorded in vitro shares many of the physiological and pharmacological
      properties of theta rhythm observed in vivo.

PMID- 9579322
TI  - Metabolic drug interactions with selective serotonin reuptake inhibitor (SSRI)
      antidepressants.
AB  - The selective serotonin reuptake inhibitor (SSRI) antidepressants have become an
      important component of the therapeutic armamentarium in psychiatry and have
      attracted a great deal of public attention. Another interesting aspect of the
      SSRIs is their interaction with various isozymes of the cytochrome P450 (CYP)
      system which are responsible for metabolism of numerous drugs. This effect on the
      CYP isozymes has drawn attention to the importance of metabolic drug-drug
      interactions when dealing with drugs used to treat psychiatric disorders. Such
      interactions are of great relevance since psychiatry patients are frequently
      treated with multiple drugs and often these drugs undergo extensive
      biotransformation to metabolites which contribute to therapeutic and/or adverse
      effects. The present review deals with various aspects of metabolism mediated by
      CYP isozymes, particularly as they relate to pharmacokinetic interactions between
      the SSRIs and other drugs which are coadministered with them.

PMID- 9579323
TI  - Dopamine D1-like receptors and reward-related incentive learning.
AB  - There now is general agreement that dopaminergic neurons projecting from ventral
      mesencephalic nuclei to forebrain targets play a critical role in reward-related
      incentive learning. Many recent experiments evaluate the role of dopamine (DA)
      receptor subtypes in various paradigms involving this type of learning. The first
      part of this paper reviews evidence from these studies that use antagonists or
      agonists relatively specific for D1- or D2-like receptors in operant paradigms
      with food, brain stimulation, self-administered stimulant or conditioned rewards
      or place conditioning. The focus is on studies that directly compare agents
      acting at the two DA receptor families, especially those studies where the agents
      produce differential actions. Results support the conclusion that D1-like
      receptors play a more critical role in reward-related learning than D2-like
      receptors. D1-like receptors initiate a cascade of intracellular events including
      cyclic adenosine monophosphate (cAMP) formation and activation of cAMP-dependent
      protein kinase (PKA). The final section of this paper reviews evidence from a
      wide range of neuroscience experiments that implicates the cAMP/PKA pathway in
      learning in general and in reward-related incentive learning in particular. We
      conclude that the molecular mechanism underlying DA-mediated incentive learning
      may involve DA release in association with reward, stimulation of D1-like
      receptors, activation of the cAMP/PKA cascade and additional intracellular events
      leading to modification of cortico-striatal glutamatergic synapses activated by
      stimuli encountered in close temporal contiguity with reward. Thus, when reward
      related incentive learning takes place, it may be the action of DA acting at D1
      like receptors that leads to plastic changes in the striatum that form the
      substrate of that learning.

PMID- 9579324
TI  - Modulation of the induction or expression of psychostimulant sensitization by the
      circumstances surrounding drug administration.
AB  - The conditions necessary to induce psychomotor sensitization and to promote its
      expression are not well understood. Two examples are reviewed here of how the
      circumstances surrounding drug administration ("set and setting") can powerfully
      modulate the sensitization produced by psychostimulant drugs, such as amphetamine
      or cocaine. In the first example it is suggested that repeated exposure to
      psychostimulant drugs may induce "neural sensitization" (i.e., produce relevant
      adaptations in the nervous system). The circumstances surrounding drug
      administration may determine, however, whether neural sensitization is expressed
      in behavior. In the second example it is suggested that the circumstances
      surrounding drug administration may determine whether sensitization is induced at
      all, or at least the rate and extent of sensitization produced by a given dose of
      a drug. It is concluded that psychomotor sensitization is not an inevitable
      consequence of exposure to psychostimulant drugs, but is the result of
      interactions amongst the pharmacological actions of drugs and the circumstances
      surrounding drug administration.

PMID- 9579325
TI  - Is there a neural code?
AB  - Rate coding and temporal coding are two extremes of the neural coding process.
      The concept of a stationary state corresponds to the information processing
      approach that views the brain as a decision maker, adopts rate coding as its main
      strategy and endorses the single- or few neuron approach. If information derived
      from sensory stimulation is used to continuously update the brain's internal
      representation of the world, then neural codes may change with time through
      learning. As a consequence, the same spike sequence may be interpreted
      differently (or evoke a different behavior) later in the day. This non-stationary
      viewpoint is embodied in the representational model of brain function that
      stresses learning and plasticity and employs temporal coding in neural
      assemblies. We argue that the switching between quasi-stable brain states as a
      result of learning is more relevant than the neuronal patterns, and the
      correlations between them, that are found during stationary states. The neural
      code likely resides in the activity patterns that cause this state-switching.

PMID- 9579326
TI  - Simultaneous comparison of cerebral dialysis and push-pull perfusion in the brain
      of rats: a critical review.
AB  - Over the last 30 years, studies of the in vivo activity of neurotransmitters and
      other endogenous factors in the brain have comprised a major effort in the
      neurosciences. Historically, the technology of push-pull perfusion was utilized
      as a major approach to investigations in this field. In the last 10 years,
      cerebral dialysis has been used as an alternative method essentially for the same
      scientific purpose, since the perfusion technique was viewed as difficult and
      excessively damaging to tissue. This review considers the representative
      literature in which both systems have been used to study local neurochemical
      responses to a drug or other chemical factor, a physiological condition or other
      situation. In addition, new experiments have been undertaken to compare, in the
      same animal and at the same time, the utility and properties inherent in the
      techniques of push-pull perfusion and cerebral dialysis in terms of the profile
      of a neurotransmitter activity and their local histopathological effects. A
      miniaturized 33/26 ga push-pull needle and a 24 ga dialysis probe were implanted
      simultaneously in the left and right caudate nuclei, respectively, in the
      anesthetized rat. An artificial cerebrospinal fluid (CSF) was perfused
      simultaneously through both devices at a rate of 10 microliters/min in the push
      pull cannula and at 1.0 or 2.0 microliters/min in the dialysis probe. Within a
      series of 8-10 successive perfusions, excess K+ ions in a concentration of either
      30 or 60 mM were incorporated in the CSF and delivered simultaneously to both the
      push-pull cannula and dialysis probe. Samples of perfusate and dialysate were
      assayed chromatographically by coulometric HPLC detector and quantitated in terms
      of the pg/min efflux of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC),
      homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The results
      showed that the resting level of DA was almost undetectable in dialysate samples
      from either structure; in push-pull perfusates the recovery of DA ranged between
      7.0 to 10.0 pg/min, which was increased threefold by excess K+ ions. The recovery
      of DA and the three metabolites in samples of push-pull perfusate was two to four
      times that in samples of dialysate during the condition of excess K+ ions. Post
      mortem histological analysis of the sites of perfusion and dialysis revealed
      little or no differences in the cytological damage induced by either the
      perfusion needle or dialysis probe. Finally, the advantages and limitations of
      each of these two experimental approaches to in vivo analysis of neurotransmitter
      efflux are reviewed in relation to the selection of an open or closed system for
      the on-line study of in vivo neurochemical events.

PMID- 9579327
TI  - Cytokines in dementia of the Alzheimer's type (DAT): relevance to research and
      treatment.
AB  - There is indirect evidence suggesting that some cytokines may be involved in the
      pathophysiology of dementia of the Alzheimer type (DAT). Measurement of
      proinflammatory cytokines in the biologic fluids and brain tissues of DAT
      patients have provided some support for such a role. However, these studies are
      limited in scope and have included a relatively small number of patients. Future
      studies are needed to elucidate the role of cytokines in the pathogenesis and
      treatment of DAT.

PMID- 9579328
TI  - Responses of the nervous system to low frequency stimulation and EEG rhythms:
      clinical implications.
AB  - The present paper reviews literature data on the role of the non-specific central
      nervous system response mechanisms on the therapeutic effects of relatively weak
      external stimulations used in clinical practice. The factors affecting the
      stimulation efficiency and increased sensitiveness of living things to extra-low
      frequency periodic stimulations (in the range of from less than 1 Hz to tens of
      Hz) are discussed. Among the factors determining such effects, the non-specific
      response mechanisms of the nervous system, the resonance phenomena in different
      organism systems, and the interaction of external stimulation with endogenous
      rhythmic processes are analyzed. Most attention is given to endogenous rhythms of
      the electrical brain activity reflected in the EEG rhythms. A high resolution EEG
      processing approach that is used to reveal the intrinsic oscillators in the
      individual EEG spectrum is described. Synchronization of sensory stimulation
      parameters with the frequencies of intrinsic EEG oscillators is supposed to be an
      appropriate way to enhance the therapeutic effects of various sensory stimulation
      treatments. Specific methods for utilizing resonance therapy via sensory
      stimulation with intrinsic EEG frequencies, and for automatic modulation of
      stimulation parameters by endogenous organism rhythms are delineated; some
      preliminary results are described.

PMID- 9579329
TI  - The origins of cerebral asymmetry: a review of evidence of behavioural and brain
      lateralization in fishes, reptiles and amphibians.
AB  - Early evidence for lateralization at a population and/or individual level in
      'lower' vertebrates is reviewed. The lateralities include structural asymmetries
      in the epithalamus of several species of fish and amphibians, asymmetries in the
      location of both eyes on the same side of the head and of the dorsal/ventral
      crossing at optic-chiasma in flatfish, asymmetries in copulatory organs of
      several species of fishes, asymmetries in lung size and direction of coiling in
      reptiles, and asymmetrical distribution of scarring in whitefish. More recent
      data on functional lateralization at population level in lower vertebrates are
      also reviewed. These include: lateral asymmetries in the direction of turning
      during escape behaviour and in eye use in poeciliid fish; lateralization of
      pectoral stridulation sounds in catfish; neural lateralization for control of
      vocalization in the frogs; pawedness in toads; lateralization of courtship
      behaviour in newts; and lateralization of aggressive responses in lizards.
      Several cases of behavioural asymmetries at the individual level are also
      described, and possible relationships between lateralization at the individual
      level and fluctuating asymmetries arising from reduced heterozygosity are
      discussed. It is argued that the overall evidence now available supports the
      hypothesis of an early origin of brain lateralization in vertebrates.

PMID- 9579330
TI  - Normal body temperature of rats: the setpoint controversy.
AB  - Emotional hyperthermia, circadian variations and the rise of body temperature
      related to exercise, have all been attributed to setpoint temperature shifts. The
      accepted theory holds that core temperature is regulated by corrective
      thermoregulatory responses opposing the core temperature deviations from the
      setpoint level. However, in fever and anapyrexia the thermoregulatory responses
      appear to be not corrective but helping, that is in the same direction as the
      core temperature deviation. A supplementary ad hoc hypothesis that setpoint level
      shifts explains why the thermoregulatory responses still could be considered
      "corrective" in spite of being in the same direction as the core temperature
      deviation. But supplementary ad hoc hypotheses immunize a theory to experimental
      challenges and therefore can no longer be considered a scientific theory. The
      present work shows that most of the arguments adduced to explain almost every
      biothermal phenomenon as being due to setpoint shifts cannot withstand a critical
      analysis.

PMID- 9579331
TI  - Brain substrates of infant-mother attachment: contributions of opioids, oxytocin,
      and norepinephrine.
AB  - The aim of this paper is to review recent work concerning the psychobiological
      substrates of social bonding, focusing on the literature attributed to opioids,
      oxytocin and norepinephrine in rats. Existing evidence and thinking about the
      biological foundations of attachment in young mammalian species and the
      neurobiology of several other affiliative behaviors including maternal behavior,
      sexual behavior and social memory is reviewed. We postulate the existence of
      social motivation circuitry which is common to all mammals and consistent across
      development. Oxytocin, vasopressin, endogenous opioids and catecholamines appear
      to participate in a wide variety of affiliative behaviors and are likely to be
      important components in this circuitry. It is proposed that these same
      neurochemical and neuroanatomical patterns will emerge as key substrates in the
      neurobiology of infant attachments to their caregivers.

PMID- 9579332
TI  - Behavior in mice with targeted disruption of single genes.
AB  - The use of mice with targeted deletion, or knockout, of specific genes provides a
      relatively new approach to establish the molecular bases of behavior. As with all
      ablation studies, the interpretation of behavioral data may be limited by the
      technique. For example, indirect effects of the missing gene may affect behavior,
      rather than the missing gene per se. Also, because the missing gene might affect
      many developmental processes throughout ontogeny and because up-regulation or
      compensatory mechanisms may be activated in knockouts, behavioral data from mice
      with targeted gene deletions should be interpreted with caution. The development
      of conditional knockouts, in which a specific gene can be inactivated any time
      during ontogeny, should allow investigators to avoid these conceptual
      shortcomings associated with behavioral data from knockouts in the near future.
      The behavioral alterations reported in knockout mice are reviewed here. Many
      dramatic changes in complex motivated behaviors including aggression, sexual,
      ingestive, and parental behaviors, have been reported for knockouts. There have
      also been many reports of alterations in sensorimotor abilities and spontaneous
      activity, as well as impairments in balance, coordination, and gait. Impaired
      learning and memory have also been reported for mice with targeted disruption of
      specific genes. Taken together, the use of knockouts will provide an important
      new tool to understand the mechanisms underlying behavior.

PMID- 9579333
TI  - Evaluation of the Abbott LCx Mycobacterium tuberculosis assay in comparison with
      culture methods in selected Italian patients.
AB  - A ligase chain reaction (LCR) DNA amplification method for the molecular
      diagnosis of Mycobacterium tuberculosis (Abbott LCx MTB) was evaluated in
      comparison with solid and liquid phase culture on 622 selected samples collected
      in two large Italian hospitals, of which 310 obtained from HIV-1 positive
      patients and 312 from HIV-negative individuals. The overall prevalence of
      mycobacteria by culture was 22% (137/622), and the apparent sensitivity and
      specificity of LCx vs. culture were 87.6% and 98.2%. Of the 26 culture
      positive/LCx negative samples, 22 were positive for MOTT and 4 for M.
      tuberculosis. All 9 samples positive by LCx and negative by culture were
      classified as true positive by clinical criteria. The final values of
      sensitivity, specificity, positive predictive value and negative predictive value
      for LCx rose to 96.8%, 100%, 100% and 99.2%, respectively. The adjusted
      sensitivity of culture methods was 89.5% for solid phase and 92.7% for Bactec. In
      view of the high sensitivity on both smear-positive (100%) and smear-negative
      (92.4%) samples and of the high negative predictive value, the LCR-based
      amplification method appears suitable as a routine screening method for the rapid
      diagnosis of M. tuberculosis in high-risk patients.

PMID- 9579334
TI  - Characterization of the phenotype conferred by two different rpsL alleles coding
      for streptomycin dependence.
AB  - Two streptomycin-dependent strains of E. coli B showing different phenotypes were
      isolated. They carried different rpsL alleles which conferred two levels of
      dependence on the drug, and showed a different expression when present in
      heterozygous conditions with other rpsL alleles, coding for sensitivity or
      resistance on the drug.

PMID- 9579335
TI  - Molecular epidemiology by ribotyping and PCR-ribotyping of Enterococcus faecium
      strains isolated from intercontinental areas.
AB  - In this study classical ribotyping based on hybridization of an enteroccocal
      ribosomal operon previously cloned from Enterococcus hirae (Sechi and Daneo
      Moore, 1993) with XbaI cut chromosomal DNA and PCR-ribotyping were used to
      characterize the molecular epidemiology of 131 Enterococcus faecium, with high
      level resistance to gentamicin, isolated from different hospitals in Italy and
      the United States. The ribotyping was able to differentiate all 131 clinical
      isolates into 96 family patterns. These family patterns appeared to be useful in
      establishing epidemiological spread. The results obtained were in agreement with
      those previously published, suggesting the presence of five to six operons in the
      Enterococcus genus (Sechi et al., 1994). We performed PCR-ribotyping, based on
      conserved sequences at the 3' end of the enterococcal 16S rrn and the 5' end of
      the 23S rrn, on 131 clinical isolates as well as on several enterococcal ATCC
      strains tested. The results were then compared with those obtained with the
      classical ribotyping method. The results suggest the presence of at least four
      classes of intergenic spacers among enterococci, but these classes are not
      helpful in differentiating between Enterococci or among Enterococcal isolates.

PMID- 9579336
TI  - Kinetics of IL-8, MIP-1 alpha, TNF alpha, IL-1 beta, IL-1ra and IL-10 in human
      whole blood samples triggered by smooth and rough LPS.
AB  - An in vitro model for the study of sepsis mediators was used to investigate the
      effects of two different lipopolysaccharides (LPS), a smooth (LPS-S) and a rough
      (LPS-R) type, on the release of chemokines (IL-8 and MIP-1 alpha) and cytokines
      (TNF alpha, IL-1 beta, IL-1ra and IL-10) from human whole blood samples. TNF
      alpha level increased significantly vs. control, at 4 h and 8 h after the
      challenge with smooth and rough type of LPS respectively. Concentrations of the
      two chemokines studied, IL-8 and MIP-1 alpha, were significantly elevated
      following stimulation by both LPS, and reached concentrations significantly
      different from controls at 4, 8 and 24 h. After 24 h of incubation both LPS
      produced a significant IL-10 increase, although such change was more substantial
      with the rough type. Present data suggest an early and maintained release of
      chemokines regardless of the type of LPS used and often in absence of a
      significant increase in primary pro-inflammatory cytokines.

PMID- 9579337
TI  - Antibodies to cytomegalo and Epstein-Barr viruses in human saliva and gingival
      fluid.
AB  - The prevalence of antibodies to EBV and CMV was studied in 34 samples of whole
      saliva and gingival crevicular fluids (GCF) obtained from clinically healthy
      volunteers and compared to the corresponding antibodies present in the serum of
      each individual. Higher prevalence of serum antibodies was found to EBV (85.2%)
      than to CMV (64.7%) (P < 0.04). The percentage of saliva samples containing IgG
      and/or IgA antibodies was not significantly different for the two viruses (79.4%
      for EBV and 58.8% for CMV). However, in the GCF the percentage to EBV was lower
      32.3% as compared to 70.5% for CMV (P < 0.002). The prevalence of CMV in serum
      saliva and GCF was similar. However, while in the saliva similar levels of IgG
      and IgA were found, in the GCF IgA prevails. The picture for EBV is different: a
      similar percentage of antibodies was noticed in serum and saliva, but it was
      significantly lower in the GCF. However, antibodies to EBV were mostly IgA both
      in the saliva and the GCF. Although a similar number of samples were positive to
      both viruses in the saliva, the IgA response to EBV was higher than to CMV (P <
      0.05), while in GCF IgA response was higher to CMV (P < 0.05). Passive
      transudation rather than active transport of plasma-derived Ig is probably
      responsible for the presence of IgG, while the IgA found in saliva and GCF is
      derived from local synthesis by plasma cells rather than from selective transport
      from blood.

PMID- 9579338
TI  - Antiviral effect of trimeric 2',5'-oligoadenylic acid and some of its analogues.
AB  - The antiviral effect of 2',5'-trioligoadenylate (2',5'-A3) and some of its
      analogues was studied using several model cell culture systems and viruses: mice
      L929 fibroblast cells inoculated with vaccine virus, testicular piglet cells
      inoculated with Aueszki disease virus (strain BUK-628), and the same culture
      inoculated with a reference strain of transmissible gastroenteritis virus, strain
      Purdue-115. Our results suggest that both 2',5'-trioligoadenylate and its
      analogues are promising antiviral substances against DNA- and RNA-containing
      viruses.

PMID- 9579339
TI  - Antibody response of lions inoculated with inactivated calicivirus vaccine
      experimentally prepared.
AB  - The majority of lions and tigers in a Safari park in Japan were suffering from
      acute vesicular disease caused by a calicivirus infection. All of these animals
      were injected subcutaneously with an inactivated calicivirus vaccine
      experimentally prepared with one of the seed viruses originally isolated from
      sick lions. Seroneutralizing antibody of paired sera collected from ten female
      lions at two week intervals was measured. A significant elevation of specific
      antibody was detected in the serum samples and no local or systemic reactions
      associated with vaccination were observed.

PMID- 9579341
TI  - Hepatitis A virus detection in wastewater by PCR and hybridization.
AB  - Hepatitis A virus is a member of the Picornaviridae family and is a principal
      agent of acute hepatitis worldwide, causing from mild to severe illness. Although
      the incidence of hepatitis A is in decline, the risk of this disease is still
      high in the Mediterranean area. Detection of hepatitis A in the environment is
      difficult because this virus needs a prolonged incubation in cell culture,
      therefore we used an antigen capture PCR (AC-PCR) followed by a hybridization on
      membrane to identify HAV in wastewater samples. The raw sewage, concentrated by
      ultrafiltration, showed 8 positive samples out of 10 (80%), while after the
      oxidation step of the sewage, 2 out of 10 (20%) and 3 out of 10 (30%) were found
      positive respectively after concentration by electronegative (HAWP Millipore) and
      electropositive (1MDS Cuno-Div.) membranes. In the final effluent the positivity
      was 1 out of 10 (10%) for the electronegative membranes and 3 out of 10 (30%) for
      the electropositive membranes. Our results indicate: i) the possibility of HAV to
      cross the wastewater treatment plant and contaminate water and food (such as
      mussels); ii) PCR-hybridization as a rapid method for HAV identification in the
      environment.

PMID- 9579340
TI  - Prevalence of influenza A virus (H1N1) antibodies in bovine sera.
AB  - An H1 subtype-specific indirect ELISA was used to determine the prevalence of
      influenza A virus antibodies in a retrospective study of 2,345 bovine sera in
      Minnesota. Twenty-seven percent of the samples tested were positive, 31% were low
      positive and 42% were negative. The prevalence of antibody appeared to peak
      during the months of September to November and then again from February to March.
      A subset of the above samples was examined by hemagglutination-inhibition (HI) to
      confirm the ELISA results. A 92% correlation was found between the ELISA and
      hemagglutination-inhibition assay. Western blot analysis on a subset of ELISA
      positive sera (n = 50) confirmed the presence of antibodies to the nucleoprotein
      and H1 hemagglutinin protein of influenza A virus.

PMID- 9579342
TI  - Microbiological monitoring of Castellammare Gulf (TP) waters for their
      suitability in marine aquaculture.
AB  - A three year investigation into the microbiological conditions of the waters of
      the Gulf of Castellammare (TP) was carried out in order to evaluate the possible
      utilization of this area as an aquaculture site. Analysis of a total of 168
      samples was aimed at estimating the quantitative distribution of total and fecal
      coliforms, enterococci and halophilic vibrios. The qualitative distribution of
      Vibrio species was also studied with particular reference to potentially
      pathogenic species. Coliforms showed the highest densities (10(2)-10(3) CFU/100
      ml) in November 1993 at the coastal stations and mostly negative values during
      the subsequent samplings; in contrast, halophilic vibrios prevailed in the warm
      months. V. alginolyticus and V. fluvialis prevailed respectively among the Vibrio
      population grown at 35 and 24 degrees C, grouped in 13 and in 4 clusters at
      similarity levels of 81-96%. Quantitative data demonstrate the presence of low
      levels of microbial contamination, which suggests the general suitability of the
      area for fish farming.

PMID- 9579343
TI  - Studies on the phytoplankton populations and physico-chemical conditions of
      treated sewage discharged into Lake Manzala in Egypt.
AB  - Over a full year, the phytoplankton populations and physico-chemical conditions
      of treated sewage discharged into Lake Manzala in Egypt were investigated. Sixty
      seven species of algae were identified, 18 Cyanophyta (Cyanobacteria), 19
      Chlorophyta, 21 Bacillariophyta, 6 Euglenophyta, 2 Cryptophyta and one species
      Pyrrhophyta. Nitzschia (6 spp.), Scenedesmus (6 spp.), Navicula (4 spp.),
      Oscillatoria (4 spp.) and Euglena (4 spp.) were the most common genera. A
      remarkable seasonal variation in species composition and standing crop of the
      phytoplankton populations was noted during the study. The total phytoplankton
      standing crop appeared to be mainly dependent on the growth of certain species
      viz., Oscillatoria chalybea, O. princepes, O. tenuis, Microcystis aeruginosa,
      Anabaena constricta (Cyanophyta), Nitzschia obtusa, Bacillaria paradoxa,
      Cocconeis placentula, Cyclotella meneghiniana (Bacillariophyta), Pandorina morum,
      Volvox sp. (Chlorophyta) and Phacus curvicauda (Euglenophyta). The continuous
      presence of Anabaena constricta and Nitzschia palea was recorded in the treated
      sewage. The least represented algal divisions were Pyrrhophyta and Cryptophyta,
      both in terms of quality and quantity. The data indicate that the secondary
      effluents were unstable in their chemical features and grossly polluted.
      Therefore, the treatment systems must treat the discharged sewage to a tertiary
      level before discharging into Lake Manzala.

PMID- 9579344
TI  - The effect of trimeric 2',5'-oligoadenylic acid and its epoxy-derivative on human
      immunodeficiency virus (HIV-1) reproduction and retroviruses reverse
      transcriptase activity.
AB  - The effect of trimeric 2',5'-oligoadenylic acid (2',5' A3) and its epoxy
      derivative (2',5'-A2 (RAA) on human immunodeficiency virus (HIV-1) reproduction
      was studied. An HIV-1 infectivity titer decrease was shown on the model of
      limphoblastoid cells when the substances under study were used. The
      interferonogenic effect of both substances was discovered. 2',5'-A2 (RAA)
      inhibited the activity of retrovirus reverse transcriptase (a C-type).

PMID- 9579345
TI  - Comparative analysis of two systems for HCV genotyping.
AB  - The HCV genotype can be determined by PCR using nested primers to structural or
      non-structural HCV regions, followed by hybridization analysis of the amplified
      products. In this study, two different systems, both based on PCR and
      hybridization analysis, were used to determine HCV genotype in 32 HCV positive
      patients at the Clinic of Infectious Diseases, University of Chieti. The main
      difference between these commercially available systems lies in the different PCR
      target. Amplification of PCR targets was obtained from all samples. Hybridization
      analysis gave unequivocal results for all samples with both methods, yielding a
      100% rate of genotype determination, with a complete correlation at the genotype
      level. A lower concordance at subtype level (65% concordance) was found, due only
      to two types of discrepancies. Both methods proved easy to use in our hands,
      adding evidence to their potential usefulness and reliability in clinical
      settings.

PMID- 9579346
TI  - Persistence of antibodies to Mycoplasma agalactiae in vaccinated sheep.
AB  - We report the results of a study on the persistence of antibodies to Mycoplasma
      agalactiae in two groups of sheep inoculated with inactivated vaccines: a vaccine
      in aluminium hydroxide adjuvant and a vaccine in mineral oil adjuvant. Antibody
      titers were evaluated monthly for a period of 11 months, using an ELISA test
      prepared with Mycoplasma agalactiae membrane antigen. The antibody titers of the
      group inoculated with the mineral oil vaccine were significantly higher than
      those of the group inoculated with the aluminium vaccine and they remained at
      high levels for up to 11 months. The antibody titers of the group inoculated with
      the aluminium vaccine 3 months after the vaccination decreased to the values
      observed before the vaccine inoculation.

PMID- 9579347
TI  - Treatment and retreatment for lice.

PMID- 9579348
TI  - A diagnostic approach to chest pain based on history and ancillary evaluation.
AB  - Pain is a major reason patients seek health care. Chest pain, in particular, is a
      serious concern for patients and clinicians because of its potentially life
      threatening implications--misdiagnosis can be fatal. Diagnosis of chest pain is
      complicated by shared neurologic pathways for thoracic and abdominal visceral
      organs. The importance of a medical history in the differential diagnosis is
      discussed. A helpful mnemonic is offered both as an organizational guide for
      novice practitioners and as a reminder for the seasoned clinician. Included are
      detailed discussions regarding the neuroanatomy of chest pain, followed by common
      historical presentations and physical findings related to selected cardiovascular
      and noncardiovascular etiologies of the condition. A brief discussion of
      confirmatory laboratory evaluations is included. Several etiologies not discussed
      in detail are presented in table format.

PMID- 9579349
TI  - Improving patient success with oral contraceptives: the importance of counseling.
AB  - Oral contraceptives (OCs) are highly effective in protecting against pregnancy if
      used correctly and consistently. They also offer noncontraceptive health
      benefits. The prescriber must understand the myriad factors contributing to
      success with OCs and other birth control methods, including characteristics and
      habits of successful users, real and perceived fears about adverse effects, and
      packaging issues. A woman's experiences with previous methods influence later
      success or failure with OCs.

PMID- 9579350
TI  - Primary care of the older adult with end-stage Alzheimer's disease.
AB  - End-of-life care is slowly being recognized as a dimension of primary care.
      Although terminal care programs have been established largely in response to the
      needs of cancer and AIDS patients, few clinical guidelines exist for end-of-life
      care in other diagnostic categories. Hospice philosophy and the palliative care
      literature provide the grounds for designing primary care approaches for a
      variety of noncancer, terminally ill patients. A growing need for
      hospice/palliative care exists for end-stage Alzheimer's patients. This article
      describes end-stage Alzheimer's disease and proposes ways a primary care provider
      may participate in the terminal care process. A patient education handout
      discussing end-stage Alzheimer's disease issues and providing family resources is
      presented.

PMID- 9579351
TI  - Promoting health in children with atopic dermatitis.
AB  - Atopic dermatitis (AD), or eczema, can be a very challenging disease to manage.
      The etiology of the disease is not completely understood, and its incidence has
      risen in the past 10 years to more than 10% of the population. AD is
      characterized primarily by intense itching and the development of papules, scaly
      lesions, fissures, and crusting. The onset occurs primarily in childhood, and
      much of the disease management is conducted by the family. Patients and their
      families often experience multiple recurrences and exacerbations, repeated
      attempts at cures and treatments, lowered self-esteem of the child, impaired
      growth and development of the child, loss of sleep, discipline problems, and
      multiple clinic and emergency department visits for exacerbations. Management
      primarily consists of prevention (i.e., good daily skin care and management of
      environmental trigger factors such as infection, irritants, emotional stress, and
      allergens). These children and their families need education and the support of
      health care professionals. This article outlines specific techniques to help
      parents and children manage AD at home and minimize exacerbations.

PMID- 9579353
TI  - News from the 5th Conference on Retroviruses and Opportunistic Infections.

PMID- 9579352
TI  - A comparison of the evaluation and treatment of cervical dysplasia by
      gynecologists and nurse practitioners.
AB  - Cervical dysplasia, a precursor to cervical cancer, affects approximately 6% to
      10% of women in the United States. Although cervical dysplasia traditionally is
      diagnosed and treated by gynecologists, nurse practitioners with special
      education and expertise in the evaluation and treatment of the condition have
      begun providing care to many women in rural and other medically underserved areas
      where there is limited access to specialized physicians. This study compared
      cervical dysplasia evaluation and treatment techniques of 11 gynecologists and 6
      nurse practitioners using abstracted patient records. The MDs showed a greater
      variation in performance than nurse practitioner colposcopists (NPCs) when
      evaluated on 10 criteria. NPC practices fell within the range of MDs, and when
      they were statistically different, NPC practices were more consistent with
      generally accepted medical practice. These data suggest that NPCs were more
      likely to adhere to a consistent set of practices. It can be concluded that NPCs
      are viable alternative providers in the evaluation and treatment of cervical
      dysplasia.

PMID- 9579354
TI  - Alpha B-crystallin in the mammalian inner ear.
AB  - To study the distribution of alpha B-crystallin, formalin-fixed preparations of
      the inner ear of the rat, cynomolgus monkey, rhesus monkey and human were stained
      immunohistochemically for alpha B-crystallin. In all cochleae investigated,
      intense staining for alpha B-crystallin was found in the inner and outer pillars
      as well as in the cells of Hensen and Claudius. In the primate inner ear, alpha B
      crystallin was also present in the polygonal epithelial cells of Reissner's
      membrane, the interdental cells and some fibrocytes of the spiral limbus,
      epithelial cells of the outer spiral sulcus and the Schwann cells of the 8th
      nerve. In the primate stria vascularis, alpha B-crystallin was mainly seen in the
      basal cell layer and the adjacent cells of the connective tissue layer. alpha B
      crystallin was found to be present in a large variety of cells in the inner ear
      surrounding the scala media.

PMID- 9579356
TI  - Time course of eye nystagmus and body movement after peripheral vestibular
      lesions in guinea pigs.
AB  - Body movement of guinea pigs was measured using a force platform at various times
      before and after unilateral end organ ablation and before and after sham surgery.
      Both spontaneous and drop-evoked movement patterns differed in the same animal
      after vestibular ablation and from control animals that received sham lesions.
      Whereas measures of eye nystagmus disappeared by 48 h postablation, measures of
      body movement indicated persistent differences even at 72 h. We conclude that the
      force platform can differentiate between movement patterns of normal and
      vestibular-lesioned animals and, in fact, measures a vestibular deficiency that
      is independent of eye nystagmus. The force platform appears to be a useful
      addition to evaluate vestibular deficits as well as to detect any benefits of
      pharmacological or surgical therapies.

PMID- 9579355
TI  - Clonal expansion of T-cell receptor beta gene segment in the retrocochlear
      lesions of EAE mice.
AB  - It has been reported that the T cell receptor V beta 8.2 (TcrbV8.2) gene segment
      is predominantly expressed in encephalomyelitic T cells responding to myelin
      basic protein (MBP) in experimental allergic encephalomyelitis (EAE) mice. We
      have demonstrated retrocochlear hearing loss in EAE mice in previous studies.
      Administration of a monoclonal antibody specific to the T cell receptor V beta 8
      (TcrbV8) subfamily prevented both this type of hearing loss and the central nerve
      disease. In this study, we examined the role of the TcrbV8.2 gene segment in the
      retrocochlear lesions of EAE mice. A clonal expression of T cell receptor beta
      chain gene segment (TcrbV8.2-TcrbD2-TcrbJ2.7) was identified in the retrocochlear
      lesions. The TcrbV8.2 gene segment appears to recombine only with TcrbJ2.1
      (32.1%) and TcrbJ2.7 (67.9%) gene segments. The TcrbJ2.7 gene segment has also
      been previously identified as the dominant TcrbJ gene in the lymph nodes of EAE
      mice. Only TcrbD2, with a length of 4 amino acids, was observed recombining with
      these TcrbV8.2 sequences. G and C nucleotides are predominantly expressed at the
      N regions between the V-D and D-J junctions. This dominant TcrbV gene segment
      (TcrbV8.2-TcrbD2-TcrbJ2.7) observed in the retrocochlear lesions has been
      identified in the MBP-specific T cells from the lymph nodes of EAE mice. These
      results suggest that a small subset of antigen-specific T cells migrate to, and
      expand at, the retrocochlear lesions, which leads to hearing loss.

PMID- 9579357
TI  - High-speed digital videoimaging of fast eardrum motions during Valsalva maneuver.
AB  - Digital high-speed camera systems are used to record high-frequency video-clips.
      After adapting this technology to the analysis of eardrum motions, fast motions
      of the eardrum can be recorded using an endoscope. Under specific static pressure
      conditions during the Valsalva maneuver, recordings of eardrum motions were made.
      The use of a Kodak Image Ektapro 1000 Motion Analyzer allowed only conventional
      videosignal processing and storage. A new type of data interface made it possible
      to save and process the complete video-clip digitally. Using an image-processing
      workstation and special mathematical algorithms, three-dimensional computer
      animations of fast eardrum motions under static pressure can be generated. In the
      present study, several animations of fast eardrum movements are described. High
      speed digital videoimaging is an adequate method to describe fast eardrum
      displacements under static pressure (Valsalva maneuver). It is possible to create
      visible timeshift images of separate eardrum parts during the fast Valsalva
      maneuver.

PMID- 9579358
TI  - Effects of capsaicin on human nasal mucosa.
AB  - In order to determine the effects of capsaicin on the sympathetic innervation of
      human nasal mucosa, the effects of capsaicin on the contractile response of
      isolated human nasal mucosal blood vessels to field stimulation and methoxamine
      were investigated. Results showed that capsaicin enhanced field stimulation but
      there were no effects on mucosal contraction induced by methoxamine. Likewise,
      the drug had no effects on mucosal basal tension but potentiated mucosal
      contractions by norepinephrine. The study indicated that capsaicin may increase
      sympathetic function with the potentiating effects of norepinephrine. Because no
      effects of capsaicin on the resting tension of the nasal mucosa in vitro were
      noted, it is therefore deduced that local reactions in nasal mucosa by capsaicin
      in vivo should be via central or local reflexes.

PMID- 9579359
TI  - A CT study of the course of growth of the maxillary sinus: normal subjects and
      subjects with chronic sinusitis.
AB  - We measured the maxillary sinus volume of normal children and those with
      bilateral chronic sinusitis by coronal CT scan of the paranasal sinus, and
      compared the results with findings previously obtained from adult patients. The
      distribution of mean maxillary sinus volume by age group from 4-9 to 70-79 years
      exhibited a monomodal pattern with a peak in the 20s in both the normal group and
      the surgical therapy group. The maxillary sinus volumes of children aged 10-15
      years and adults tended to be smaller in the surgical therapy group than in the
      normal group; this tendency was more prominent in the adult group. These findings
      appear to support the hypothesis that the ethmoid infundibulum and middle meatus
      are narrowed by inflammation of the ostiomeatal complex and by various bony
      anatomic variations in the nasal cavity, leading to impaired pneumatization of
      the maxillary sinus.

PMID- 9579360
TI  - Palatal mucoperiosteal free graft: another reconstruction option for oral
      defects.
AB  - Traditional methods of repair for medium-size (3-5 cm) oral defects include
      allowing granulation, primary closure, skin grafts, and buccal mucosal grafts.
      Each of these methods has several disadvantages, and all tend to result in
      significant scar contracture and often lack sufficient bulk. In 10 patients, the
      defect left by resection of cancer lesions was reconstructed with a free palatal
      mucoperiosteal graft. In all patients, the grafts survived with little
      contracture, allowing for adequate tongue mobility. Because of the thickness of
      the palatal mucoperiosteum, local depressions typically associated with floor of
      the mouth defects could be avoided. The palatal donor site was left to granulate
      and recovered in 2-3 weeks with little residual deformity. In 4 patients a
      through-and-through resection of a floor of the mouth cancer was performed in
      continuity with a neck dissection. A palatal mucoperiosteal free graft was
      utilized exclusively in the reconstruction, without the development of salivary
      fistula.

PMID- 9579361
TI  - Peritonsillar abscess associated with infectious mononucleosis.
AB  - Infectious mononucleosis (IM) is characterized as a viral disease; thus, no
      antibiotic treatment is recommended. However, some of these patients tend to
      develop a long-lasting, painful disease, which can be relieved by antibiotic
      administration. Due to this bed-side knowledge, we re-evaluated 928 patients with
      peritonsillar abscess (PA), treated during a 5.5-year period in the Department of
      Otorhinolarygology of Turku University Central Hospital. Of these patients 15
      (1.6%) also had infectious mononucleosis (IM). During this period, 64 patients
      with severe pharyngeal IM were treated in our department and thus the proportion
      of PA in patients with IM was 23.4%. A control of 15 age- and sex-matched
      patients with PA but without mononucleosis was formed in order to evaluate the
      possible differences in patient history, clinical symptoms and findings. Such
      differences were small and did not affect the chosen treatment of PA, abscess
      tonsillectomy. There was no peri- or postoperative difference in complications or
      recovery, but the hospitalization time was longer in IM patients with PA (3.1
      days) than in patients with PA only (2.4 days). IM patients referred to ENT
      departments make a special group of patients, who may also need surgical
      treatment.

PMID- 9579362
TI  - Isepamicin sulfate-induced sensorineural hearing loss in patients with the 1555 A
      ->G mitochondrial mutation.
AB  - A mitochondrial mutation at nucleotide 1555 has been reported to be susceptible
      to aminoglycoside antibiotics as well as one of the causes of nonsyndromic
      sensorineural hearing loss. We herewith report 2 cases bearing the 1555 A-->G
      mitochondrial mutation who had hearing loss after short-term exposure to the new
      aminoglycoside antibiotic, isepamicin sulfate. Even when using aminoglycoside
      antibiotics with milder side effects, careful attention should be paid in
      applying them to patients with particular genetic backgrounds.

PMID- 9579364
TI  - Localisation of ecto-5'-nucleotidase and divalent cation-activated ecto-ATPase in
      chronic tonsillitis.
AB  - The histochemical localisation of two ecto-enzymes, 5'-nucleotidase (5'-NT) and
      Mg(2+)-ATPase, was investigated in hyperplastic and recurrent tonsillitis.
      Detection of enzymes was performed on frozen sections using the classical lead
      nitrate method. Activity of 5'-NT was demonstrated particularly in the cells of
      lymphoid follicles and in the basal layer of the surface tonsillar epithelium.
      There was no difference in localisation of 5'-NT between hyperplastic and
      recurrent tonsillitis, whereas a stronger reaction in follicular mantle zones was
      observed in recurrent tonsillitis compared to hyperplastic tonsillitis. Mg(2+)
      ATPase activity was mainly associated with the cells lining the tonsillar crypt,
      with the interfollicular areas and blood vessels. In recurrent tonsillitis only
      half of the studied follicular germinal centres expressed Mg(2+)-ATPase activity,
      compared to hyperplastic tonsillitis. The similar localisation of 5'-NT and ecto
      ATPase in both types of chronic tonsillitis suggests that in inflamed tonsils
      expression of investigated enzymes probably does not depend on the type of
      chronic tonsillitis.

PMID- 9579363
TI  - A second primary squamous cell carcinoma arising in a radial forearm flap used
      for reconstruction of the hypopharynx.
AB  - A 63-year-old man had undergone hypopharyngectomy for hypopharyngeal carcinoma in
      1985. A free radial forearm flap was used for reconstruction of the pharynx. Ten
      years after the surgery, a second primary squamous cell carcinoma occurred in the
      neopharynx. Persistent exposure to alcohol, saliva and foodstuffs was considered
      as a possible cause of second primary carcinoma. Long-term follow-up is indicated
      in patients undergoing reconstruction using cutaneous or musculocutaneous flaps.

PMID- 9579365
TI  - Adult rhabdomyoma located near the thyroid gland. A case description.
AB  - A case of adult rhabdomyoma, a rare muscle-derived tumor, is described in a 40
      year-old man. The tumor was located in close proximity to the thyroid gland and
      was initially misinterpreted as an adenoma of the gland. The most important
      differential diagnoses are discussed including methods available for
      differentiating those from rhabdomyoma.

PMID- 9579366
TI  - Stereotactic breast biopsy: who should perform it?

PMID- 9579367
TI  - Characterization of signet ring cell carcinoma of the stomach.
AB  - BACKGROUND AND OBJECTIVES: As there is no consensus regarding the prognosis of
      patients with signet cell carcinoma of the stomach compared with other types of
      gastric cancer, we retrospectively studied the clinicopathologic features and
      prognosis of signet cell carcinoma in comparison with other types of gastric
      cancer. METHODS: Gastrectomies were performed because of gastric cancer in 1,498
      patients between 1970 and 1994. Of the 154 patients diagnosed with signet ring
      cell carcinoma, 94 had early and 60 had advanced gastric carcinoma. The
      percentage of patients with an early carcinoma was significantly higher among
      those with signet ring cell carcinoma compared with those with other gastric
      carcinoma histologies. RESULTS: The survival of the total group of patients with
      signet ring cell carcinoma was significantly better than that of patients with
      other types of gastric carcinoma (P < 0.05). Survival of the subset of patients
      with early signet ring cell carcinoma was also improved compared with patients
      with other types of gastric carcinoma (P < 0.05). However, patients with advanced
      signet ring cell carcinoma had a poor prognosis similar to that of patients with
      other types of gastric carcinoma.

PMID- 9579368
TI  - Cyclophosphamide given after active specific immunization augments antitumor
      immunity by modulation of Th1 commitment of CD4+ T cells.
AB  - BACKGROUND AND OBJECTIVES: In order to evaluate the regulatory effect of
      cyclophosphamide (CPA) on active specific immunization (ASI)-induced antitumor
      immunity, we examined the timing of CPA (100 mg/kg) with ASI, and focused on
      whether CPA given after ASI augments antitumor immunity by modulation of Th1
      commitment of CD4+ T cells. METHODS: We examined the effect of CPA combined with
      ASI using sonicated tumor supernatant (SS) and recombinant interleukin-1 beta
      (rIL-1 beta). RESULTS: Survival of i.p. tumor inoculated mice after ASI (days 
      12, -9, and -6) followed by 100 mg/kg CPA (day -3) (ASI-CPA) was significantly
      prolonged compared with that of mice treated with ASI alone, whereas CPA (day 
      15) treatment before ASI (CPA-ASI) completely abrogated the survival prolongation
      by ASI alone. In early stage (day 0) after ASI-CPA treatment, the CD4+ T cells
      were determined to play an important role in the protective immunity for the
      following reasons: 1) the CD4+/CD8+ ratio of spleen cells from immunized mice was
      higher than that of the control or CPA alone treated group; and 2) the tumor
      neutralizing activity of fresh spleen cells was abrogated by CD4+ T-cell
      depletion in vitro. CD4+ T cells of mice treated with ASI-CPA produced more
      interferon (IFN)-gamma and IL-2 and less IL-4 than those of the ASI alone group.
      CONCLUSIONS: These results suggest that the protective immunity induced by ASI
      was augmented through the modification of the Th1 and Th2 balance by CPA
      injection after ASI.

PMID- 9579369
TI  - Factors affecting survival following local, regional, or distant recurrence from
      localized melanoma.
AB  - BACKGROUND AND OBJECTIVES: Approximately one third of all melanoma patients will
      experience disease recurrence. Factors that affect patient survival following
      local, regional, or distant first recurrences of localized melanoma are the
      subject of this investigation. METHODS: Survival times for a total of 1,085 first
      recurrences from 4,568 localized melanoma patients were examined in relationship
      to patient and disease factors by Cox regression. Nearly half (48.8%) of all
      first recurrences were regional, 21.8% were local, and 29.4% were distant
      recurrences. RESULTS: Survival following recurrence differed significantly by
      site of recurrence (local, regional, or distant; P < 0.0001). Within each site,
      the median survival time did not differ by time of recurrence following
      diagnosis. Significant tumor factors for survival following local recurrence
      included tumor thickness (P = 0.0263) and lesion location (P < 0.0001). For
      regional recurrences, survival was significantly related to ulceration (P =
      0.0105) and whether the recurrence was combined with a local recurrence (P =
      0.0429). Survival following distant metastasis was related to number of distant
      sites (P < 0.0001) and whether a visceral site was involved (P < 0.0001).
      CONCLUSIONS: Patient and tumor characteristics predict survival following
      recurrence. Regardless of disease-free interval, long-term follow-up of melanoma
      patients is necessary. Patients experiencing distant metastasis have the shortest
      median survival time compared to patients experiencing local or regional
      recurrences.

PMID- 9579370
TI  - Application of the differential hybridization of Atlas Human expression arrays
      technique in the identification of differentially expressed genes in human
      glioblastoma multiforme tumor tissue.
AB  - BACKGROUND AND OBJECTIVES: Several molecular biology techniques are utilized to
      study changes in gene expression during the genesis of human tumors. Our
      objective was to identify genes that showed altered expression between normal
      brain tissue (NBT) and glioblastoma multiforme tumor tissue (GMTT). METHODS: The
      technique of differential hybridization of two Atlas Human cDNA expression array
      was used. In this technique, dCTP32-labeled complimentary DNA from NBT and GMTT
      was hybridized to two identical human cDNA expression array membranes containing
      588 known genes. RESULTS: Autoradiographic analysis showed that of the 588 genes
      analyzed, 52 are overexpressed in GMTT and 57 in NBT. A gene-specific
      semiquantitative reverse transcription polymerase chain reaction (RT-PCR) method
      was used to confirm the expression pattern of seven known genes. RT-PCR results
      demonstrate that the expression pattern of a majority of genes agreed with the
      expression pattern observed on expression array. The known tumor suppressor genes
      retinoblastoma (RB) and p53 showed loss of expression in GMTT compared with NBT.
      CONCLUSIONS: We conclude that the differential hybridization technique of Atlas
      Human cDNA expression array can be a useful method in identifying genes that are
      differentially expressed either in NBT or GMTT.

PMID- 9579371
TI  - Delayed cellulitis associated with conservative therapy for breast cancer.
AB  - BACKGROUND AND OBJECTIVES: Delayed breast cellulitis is an infrequently reported
      entity after conservation therapy for breast cancer. We describe our experience
      with this entity at Naval Medical Center, San Diego. METHODS: Eight patients who
      presented with delayed cellulitis after wide local excision/axillary dissection
      and breast radiotherapy (RT) are presented. Their clinical characteristics and
      therapy are described and possible causative factors are analyzed. RESULTS: The
      latency of breast cellulitis is variable after breast conservation therapy,
      although most cases in our experience and in the literature occur within a year
      post-RT. These infections are frequently refractory to a single course of
      antibiotics (n = 4 cases in our experience). Some patients suffer multiple
      episodes separated by months. CONCLUSIONS: Breast cancer patients are at risk for
      delayed cellulitis after conservative surgery and RT. The mechanism of such
      events probably involves lymph stasis, however, therapy is no different from the
      more frequently occurring cases of cellulitis presenting perioperatively.

PMID- 9579372
TI  - Clinical management of nonpalpable or small breast masses by fine-needle
      aspiration biopsy (FNAB) under ultrasound guidance.
AB  - BACKGROUND AND OBJECTIVES: Open breast biopsy of palpable breast masses is widely
      accepted. Now, the use of high-resolution, real-time ultrasound (US) makes it
      easy to detect nonpalpable or small breast nodules, as well as palpable breast
      masses. METHODS: We performed fine-needle aspiration biopsy (FNAB) under US
      guidance to manage the nonpalpable or small breast masses detected by US
      examination and to distinguish between benign and malignant tumors. To
      investigate the usefulness and sensitivity of FNAB under US guidance, we reviewed
      a total of 137 FNAB records for cases diagnosed between January 1993 and December
      1994. RESULTS: Fifty-five cases were classified as benign, 70 as
      atypical/indeterminate, 1 as suspicious/probably malignant, 6 as malignant, and 5
      as unsatisfactory. Of these, five cases were confirmed as malignant, but one case
      showed no malignancy at surgery. Four cases were nonpalpable breast cancer, two
      were in stage 0, and two were in stage I. One case in the suspicious/probably
      malignant group on the initial FNAB was shown to be malignant by re-aspiration on
      follow-up study. The sensitivity of FNAB under US guidance was 83.3% (5/6) and
      the specificity was 99.2% (125/126). The diagnostic accuracy was 83.3% (5/6) and
      the negative predictive value was 99.2% (125/126). CONCLUSIONS: FNAB under US
      guidance is useful for the management of nonpalpable or small breast masses; it
      is sensitive for distinguishing between benign and malignant tumors and may
      reduce unnecessary surgical procedures and replace conventional manual aspiration
      biopsy.

PMID- 9579373
TI  - Radiolocalization of the sentinel lymph node in Merkel cell carcinoma: a clinical
      analysis of seven cases.
AB  - Merkel cell carcinoma (MCC) is a rare cutaneous skin lesion with a variable but
      often aggressive clinical course. Patient survival correlates with nodal status
      and the presence of distant metastases. The histologic status of the sentinel
      lymph node consistently correlates with the incidence of regional lymphatic
      metastases in other dermal malignancies. The technique of radiolocalization and
      surgical resection of the sentinel lymph node using an intraoperative gamma probe
      is used to guide clinical management in these patients. We report on seven cases
      of MCC managed utilizing this technique. Four patients had negative sentinel
      nodes and no other nodal disease at completion lymphadenectomy (n = 2) or
      clinical follow-up (n = 2) and currently remain disease free. Two patients had a
      positive sentinel node but no other positive lymph nodes at completion
      lymphadenectomy; one of them developed regional recurrence. One patient with a
      positive sentinel node and six additional positive nodes developed extensive
      nodal disease and systemic recurrence during radiotherapy and expired of MCC. Our
      results suggest that the sentinel node was identified and removed successfully
      using radiolocalization making this technique useful in the staging and therapy
      of patients with MCC.

PMID- 9579375
TI  - Localized limb cutaneous metastases.
AB  - Cutaneous metastatic disease may be evident in a variety of forms and locations.
      Anatomically, it may on occasion be confined as localized limb metastases. We
      report on two patients with localized limb metastases, one from melanoma and the
      other from Merkel cell carcinoma. Patients with localized limb metastasis have a
      poor prognosis; however, treatment options not available for generalized
      cutaneous metastatic disease, such as amputation or isolated limb perfusion with
      chemotherapeutic agents, can be at times be beneficially employed.

PMID- 9579374
TI  - Cortical metastatic lesions of the appendicular skeleton from tumors of known
      primary origin.
AB  - BACKGROUND AND OBJECTIVES: Metastatic disease represents the most common
      neoplastic process involving bone. Recently, a small subset of cortical based
      metastatic lesions has been identified. We attempted to delineate the incidence,
      origin, location, and possible significance of these lesions within an
      orthopaedic patient population. METHODS: A chart and radiographic review of
      patients treated for metastatic disease to bone over a 17-year period was
      performed. Inclusion criteria for lesions were as follows: 1) an appendicular
      skeletal site, 2) histopathologic confirmation of origin, and 3) presence within
      a patient diagnosed with a single, known neoplastic process. The lesions were
      classified as either cortical or medullary based. RESULTS: Eighty-three lesions
      (70 patients) satisfied inclusion criteria. Most lesions were of pulmonary (26),
      breast (22), renal (16), or prostatic (8) tumor origin. Eighteen lesions (22%)
      from 15 patients were identified as cortical and represented initial presentation
      in 7 patients. These lesions were of pulmonary (11), renal (5), and breast (2)
      tumor origin. CONCLUSIONS: Cortical based metastases within the appendicular
      skeleton may occur more frequently than previously expected. While tumors of
      pulmonary and renal origin accounted for 42 of the 83 (51%) appendicular lesions,
      they were responsible for 16 of the 18 (89%) cortical metastases. This
      preponderance of pulmonary and renal metastases to the cortex is consistent with
      previously published reports. Our findings may be of value when diagnosing and
      treating patients whose initial presentation is a cortically based lesion.

PMID- 9579376
TI  - Nasal reconstruction for malignant melanoma.

PMID- 9579377
TI  - Breast cancer genes and the surgeon.
AB  - Two genes, called BRCA-1 and BRCA-2, have been identified that appear to be
      responsible for the majority of familial breast cancer syndromes. These genes now
      play a prominent role in the practice of the surgeon treating breast cancer.
      Additional genes, PTEN (Cowden disease), MSH1 or MLH2 (HNPCC), and p53 (Li
      Fraumeni syndrome) are responsible for other breast cancer syndromes but have not
      yet entered the clinical arena on a large scale. The risk of breast and ovarian
      cancer by age 70 in a BRCA-1 mutation carrier is estimated at 55-75% and 16-26 %,
      respectively, overall, and as high as 87% and 44% in those with a strong family
      history. The cancer risks associated with BRCA-2 mutations appear to be somewhat
      lower than those of BRCA-1. BRCA mutations show a strong founder effect. This is
      best recognized in the Ashkenazi Jewish community, in which the incidence of one
      of three characteristic mutations is about 2%. In other ethnic groups the pattern
      of mutations is different, with over 100 distinct mutations throughout the genes
      having been described. Most mutations so far have been frame-shift or mis-sense
      mutations, although large deletions have also been described. Thus, in most
      situations, assessment of the whole coding sequence is required to confirm or
      exclude a mutation. Guidelines to suggest who is likely to be a mutation carrier
      are being clarified, but the appropriate management of someone who tests positive
      remains difficult. Prophylactic mastectomy and oophorectomy are likely to offer
      substantial gains in life expectancy to mutation carriers, especially for young
      women with a strong family history. Unfortunately, there are no currently
      available strategies to eliminate the risk of breast or ovarian cancer. The
      psychological impact of testing also remains poorly understood, and the danger of
      various forms of discrimination remain. These factors must be clearly understood
      by all parties prior to testing. The process of a dynamic, interactive informed
      consent--much more than a simple printed document--and also counseling are
      central to the testing process.

PMID- 9579378
TI  - Iron chelation therapy: the need for orally active drugs.

PMID- 9579379
TI  - DHEA: a biologic conundrum.

PMID- 9579380
TI  - Lead's toxic legacy for human reproduction: new studies establish significant
      bone lead release during pregnancy and nursing.

PMID- 9579381
TI  - Prostate-specific antigen (hK3) and human prostatic glandular kallikrein (hK2) in
      the detection of early stage human prostate cancer.

PMID- 9579382
TI  - New insight into coronary endothelial dysfunction: role of endothelin.
AB  - The coronary endothelium plays a central role in the modulation of coronary
      vascular tone via the production and release of vasoactive mediators. A number of
      cardiovascular disease states are associated with coronary endothelial
      dysfunction, which results in an imbalance between vasoactive substances.
      Endothelin is a potent vasoconstrictor produced by the coronary endothelium and
      has been implicated in the pathogenesis of coronary endothelial dysfunction. This
      review examines the relationship between endothelin and coronary endothelial
      dysfunction as it occurs in a number of cardiovascular disease states and
      explores potential therapeutic options.

PMID- 9579383
TI  - Pyridoxal isonicotinoyl hydrazone and its analogs: potential orally effective
      iron-chelating agents for the treatment of iron overload disease.
AB  - At present, the only iron (Fe) chelator in clinical use for the treatment of Fe
      overload disease is the tris-hydroxamate deferoxamine (DFO). However, DFO suffers
      from a number of disadvantages, including the need for subcutaneous infusion (12
      to 24 hours a day, 5 or 6 times per week), its poor intestinal absorption, and
      high cost. Therefore, there is an urgent need for an efficient, economical, and
      orally effective Fe chelator. Pyridoxal isonicotinoyl hydrazone (PIH) is a
      tridentate Fe-chelating agent that shows high Fe chelation efficacy both in vitro
      in cell culture models and also in vivo in rats and mice. In addition, this
      chelator is relatively nontoxic, economical to synthesize, and orally effective,
      and it shows high selectivity and affinity for Fe. However, over the last 10
      years the development of PIH and its analogs has largely been ignored because of
      justifiable interest in other ligands such as 1,2-dimethyl-3-hydroxypyrid-4-one
      (L1). Unfortunately, recent clinical trials have shown that significant
      complications occur with L1 therapy, and it is controversial whether this
      chelator is effective at reducing hepatic Fe levels in patients. Because of the
      current lack of a clinically useful Fe chelator to replace DFO, PIH and its
      analogs appear to be potential candidate compounds that warrant further
      investigation. In this review we will discuss the studies that have been
      performed to characterize these chelators at the chemical and biologic levels as
      effective agents for treating Fe overload. The evidence from the literature
      suggests that these ligands deserve further careful investigation as potential
      orally effective Fe chelators.

PMID- 9579384
TI  - Longitudinal changes in dehydroepiandrosterone concentrations in men and women.
AB  - Dehydroepiandrosterone, an adrenal steroid, has many purported roles in the body
      and has been used as an oral supplement in the treatment of various illnesses.
      Because little is known about normal changes over time in dehydroepiandrosterone
      concentrations, we studied the 5-year change in plasma dehydroepiandrosterone
      concentrations in 614 free-living adults. Two hundred seventy-three males and 341
      females had dehydroepiandrosterone and dehydroepiandrosterone sulfate
      concentrations measured in 1989 and 1994. Demographic data were also obtained.
      Dehydroepiandrosterone concentrations differed significantly by sex and 5-year
      age group. The average decline in dehydroepiandrosterone was 5.6%/year, and the
      rate of decline was directly related to age but not to sex, measures of
      adiposity, or serum glucose. Dehydroepiandrosterone sulfate concentrations
      differed significantly by sex and age group. The average decline in the sulfated
      hormone was 2.0%/year and was not related to age, sex, measures of adiposity, or
      serum glucose. Knowledge of the natural course of age-related changes in
      dehydroepiandrosterone and dehydroepiandrosterone sulfate concentrations is
      essential to our understanding of the relationship of dehydroepiandrosterone to
      chronic diseases.

PMID- 9579385
TI  - Mobilization of lead from the skeleton during the postnatal period is larger than
      during pregnancy.
AB  - A cohort of 15 immigrant females to Australia and 7 native Australian controls
      were monitored on a monthly basis with high-precision lead isotopic methods
      during gestation and for 6 months after pregnancy to determine the extent of lead
      mobilization from the maternal skeleton. Quarterly environmental samples of house
      dust, drinking water, urban air, gasoline, and a 6-day duplicate diet were also
      measured. The geometric mean blood lead concentration for the immigrant females
      on arrival in Australia was 3.0 microg/dl (range: 1.9 to 20 microg/dl), and for
      the Australian controls was 3.1 gm/dl (range: 1.9 to 4.3 microg/dl). During
      gestation and after pregnancy, blood lead concentrations varied, with mean
      individual changes of -14% to 83%. For the immigrant subjects, the percentage
      change in blood lead concentration was significantly greater during the
      postpregnancy period than during the 2nd and 3rd trimesters (p < 0.001). Skeletal
      contribution to blood lead, based on the isotopic composition for the immigrant
      subjects, increased in an approximately linear manner during pregnancy. The mean
      increases for each individual during pregnancy varied from 26% to 99%. Skeletal
      lead contribution to blood lead was significantly greater (p < 0.001) during the
      postpregnancy period than during the 2nd and 3rd trimesters. The contribution of
      skeletal lead to blood lead during the postpregnancy period remained essentially
      constant at the increased level of lead mobilization, although the duration of
      breastfeeding varied from 1 week to more than 6 months. The increased
      contribution of skeletal lead to blood lead during the postpregnancy period is
      attributed to increased mobilization of lead from maternal skeletal stores during
      lactation. The increased contribution of skeletal lead both during pregnancy and
      in the postpregnancy period is consistent with increased bone resorption, and may
      be associated with an inadequate calcium intake observed in quarterly 6-day
      duplicate diets. Mobilization of skeletal lead stores represents a potentially
      important source of perinatal lead intake and accumulation in the developing
      fetus. Only two subjects consumed dietary supplements for calcium, and their
      mobilization of lead from the skeleton to the blood was the lowest of all the
      subjects. These two subjects' use of calcium supplements may have reduced
      mobilization of skeletal mineral stores to supply the calcium needs of pregnancy
      and lactation. Calcium supplementation may be an important means of limiting
      fetal exposure to lead.

PMID- 9579386
TI  - Assessment of the trypsin-like human prostatic kallikrein, also known as hK2, in
      the seminal plasma of infertile men: respective contributions of an ELISA
      procedure and of Western blotting.
AB  - Human seminal plasma (SP) is a unique source of kallikreins. Prostate-specific
      antigen (hK3), which is a chymotrypsin-like human prostatic kallikrein (CHPK),
      and its cousin protein (hK2), which is recognized as a trypsin-like human
      prostatic kallikrein (THPK), have been assessed in infertility disorders to test
      the hypothesis that oligoasthenoteratozoospermia (OAT) is associated with an
      abnormal prostatic function. Monoclonal antibodies specific for THPK (hK2) were
      produced by Immunova, Canada, and used to develop a new enzyme-linked
      immunosorbent assay procedure and to perform Western blot analyses in SP. The
      immunoradiometric assay from Hybritech Inc., San Diego, Calif., was selected for
      CHPK (hK3) measurements in SP. Determinations of the THPK and of CHPK contents in
      SP from four groups of subjects were performed after validation of the assays.
      The concentration of both kallikreins was similar in three groups of infertile
      men, and no statistical difference from the control group was recorded. Western
      blot analysis confirmed the existence of different molecular forms of both
      kallikreins in SP. Generally, these molecular forms were not affected by
      infertility disorders except when obstructive azoospermia led to the exclusion of
      seminal vesicles, which are the sources of protein C inhibitor (PCI). No THPK-PCI
      complex was observed because THPK, unlike CHPK, is bound mainly to PCI within a
      few minutes after ejaculation. These data suggest that measurements of
      kallikreins in the SP of infertile men are much less useful than evaluation of
      their different molecular forms. Specifically, the absence of THPK-PCI appears to
      be a reliable feature of obstructive azoospermia, and this test should be
      routinely practiced in andrology laboratories.

PMID- 9579387
TI  - Endotoxin impairs agonist-induced calcium mobilization in bovine aortic myocytes
      by a nitric oxide-independent mechanism.
AB  - We hypothesized that endotoxin (LPS) would impair vasoconstrictor-agonist-induced
      calcium (Ca2+) mobilization by a nitric oxide (NO)-dependent mechanism. We
      incubated bovine aortic myocytes (passages 16 to 23) for 22 to 24 hours with 0 to
      1.0 mg/ml Escherichia coli lipopolysaccharide (LPS). Medium (Dulbecco's modified
      Eagle's medium (DMEM) + 10% fetal bovine serum (FBS)) was assayed for nitrite
      (chemiluminescence), and myocytes were loaded with fura-2 acetoxymethyl ester
      (fura-2AM), after which we assessed basal and thrombin (10 U/ml)-induced peak
      Ca2+ mobilization by microspectrofluorimetry. LPS (0.01 to 1.0 mg/ml) led to dose
      dependent nitrite accumulation, which was blocked by coincubation with N(omega)
      nitro-L-arginine methyl ester (L-NAME, 1 mmol/L). LPS also impaired Ca2+
      responses in a dose-dependent manner (from -13% at 0.1 mg/ml to -47% at 1.0
      mg/ml, n = 8 to 43/dose). However, coincubation with L-NAME did not ameliorate
      the Ca2+ mobilization defect (peak Ca2+ increments: control = 419 +/-30 nmol/L,
      vs LPS (1 mg/ml) = 206+/-18 nmol/L (mean+/-SE), n = 15; p < 0.001; control/L
      NAME: 417+/-31 nmol/L vs LPS/L-NAME: 212+/-19 nmol/L; n = 17 p < 0.001), despite
      inhibition of associated nitrite accumulation in the medium (control vs LPS: p <
      0.001; control/L-NAME vs LPS/L-NAME: p > 0.05; LPS vs LPS/L-NAME: p < 0.001).
      Supplemental L-arginine augmented LPS-induced nitrite generation without
      affecting Ca2+ mobilization. Indomethacin failed to prevent the LPS-induced
      decrement in thrombin response, but did inhibit LPS-induced myocyte nitrite
      production, suggesting "crosstalk" between the NO-synthase and cyclo-oxygenase
      (COX) systems. These experiments suggest that LPS-induced vascular contractile
      impairment is at least partly mediated by an NO-independent impairment of agonist
      induced myocyte Ca2+ mobilization. This further suggests that any important
      contribution of NO synthesis to LPS-induced contractile dysfunction must depend
      on impairment of the Ca2+ sensitivity of the contractile apparatus (i.e.,
      pharmacomechanical coupling).

PMID- 9579388
TI  - Eicosanoids in sickle cell disease: potential relevance of 12(S)-hydroxy
      5,8,10,14-eicosatetraenoic acid to the pathophysiology of vaso-occlusion.
AB  - The monohydroxyeicosanoid 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12
      HETE), which is derived from oxygenation of arachidonic acid by 12-lipoxygenase,
      is one of the major metabolites in platelets. In a recent study, we have showed
      that this eicosanoid stimulated basal sickle-red-cell-endothelial-cell adhesion.
      To understand the pathophysiologic significance of 12-HETE, we measured the
      levels of this eicosanoid in plasma and urine from children with sickle cell
      disease. We found that as compared with controls, plasma 12-HETE levels are
      increased in patients with sickle-cell disease in the steady state, and are
      increased further during vaso-occlusive crises. Urinary 12-HETE levels were also
      increased during the steady state. We also assessed plasma levels of soluble P
      selectin (another potential marker for platelet activation), and found changes in
      the levels of this marker similar to those seen with plasma 12-HETE. In
      additional studies, we found that 12-HETE enhanced hypoxia-induced sickle-red
      cell-endothelial adherence, and that this effect was mediated by potentiation of
      agonist-induced upregulation of the expression of the mRNA for vascular cell
      adhesion molecule-1 (VCAM-1) in endothelial cells. Because 12-HETE appears to
      enhance both basal and agonist-induced sickle-red-cell adhesion, this metabolite
      could potentially play a role in the pathogenesis of the vaso-occlusive crisis
      (VOC) in sickle-cell disease.

PMID- 9579389
TI  - Increased ascitic level of hyaluronan in liver cirrhosis.
AB  - Hyaluronan (HA) is a polysaccharide that forms a critical component of
      extracellular matrixes. It is present in high concentrations in tissues
      undergoing remodeling and morphogenesis. Serum HA is elevated in patients with
      chronic liver disease, and this has been considered to be caused by impaired
      degradation by the liver endothelial cells. We studied the level of HA in the
      ascitic fluid and plasma from 27 patients with cirrhotic ascites. These values
      were compared with peritoneal dialysate effluent (PDE) and plasma from 33
      patients with uremia who were undergoing continuous ambulatory peritoneal
      dialysis (CAPD). The median HA levels in ascitic fluid and plasma from our 26
      patients with cirrhosis were significantly higher than corresponding PDE and
      plasma values from the 33 CAPD patients (p < 0.0001). The median
      peritoneal/plasma ratios of creatinine, albumin, and immunoglobulin G in either
      cirrhotic or CAPD patients were less than unity. In contrast, the median
      peritoneal/plasma ratios of HA in both groups of patients exceeded one with a
      higher peritoneal/plasma ratio of HA in patients with cirrhosis (p = 0.0035). A
      significant correlation was observed between the ascitic level of HA and
      interleukin-1beta, interleukin-6, or transforming growth factor-beta. Our in
      vitro cell culture studies revealed that HA is synthesized by both mesothelial
      cells and macrophages. We observed an additive effect in the synthesis of HA by
      mesothelial cells when the macrophage-conditioned medium was added to the RPMI
      culture medium. We conclude that a high level of HA is found in ascites from
      patients with cirrhosis. Our results strongly suggest that simultaneous increased
      synthesis of HA by the peritoneal cells and a reduction of degradation by liver
      endothelial cells occur in these patients with cirrhosis with ascites. This event
      of increased HA synthesis may be contributory to remodeling and regeneration of
      the peritoneal lining.

PMID- 9579390
TI  - Interaction of gender and dietary protein on renal growth and the renal growth
      hormone-insulin-like growth factor axis.
AB  - The female kidney tends to be smaller, have a lower glomerular filtration rate,
      and be less susceptible to glomerulosclerosis than the male kidney. Insulin-like
      growth factor-I (IGF-I) is a peptide growth factor that appears to be important
      for normal and adaptive kidney growth. The purpose of this study was to compare
      the kidney growth response of the male and female rat kidneys to increased
      dietary protein intake and to see whether differences in IGF-I production or
      receptor expression might underlie any gender differences seen. Male (M) and
      female (F) Munich-Wistar rats (6 to 9 weeks of age) were randomized to isocaloric
      diets containing either 20% (NP) or 50% (HP) protein and studied after 3 and 14
      days. In the male rat, wet kidney weight was significantly increased with HP at
      both day 3 (M-HP 1028+/-21 mg vs M-NP 891+/-19 mg, p < 0.01) and day 14 (M-HP
      1499+/-41 mg vs M-NP 1246 +/-37 mg, p < 0.01). In contrast in the female rat,
      while there was evidence of initial increased growth at day 3 in the kidneys of F
      rats fed HP (F-HP 788+/-39 mg vs F-NP 650+/-23 mg, p < 0.01), this difference was
      not sustained at 14 days (F-HP 961+/-67 mg vs F-NP 931+/-71 mg, p = NS). At day
      3, kidneys of both male and female rats fed HP exhibited an increase in total
      protein but not DNA content. The kidneys of male rats showed increased
      protein/DNA ratios in the medulla and inner cortex, whereas in the kidneys of
      female rats, the increase in protein/DNA ratio was confined to the cortex. After
      14 days of HP ingestion, the kidneys of male rats showed increases in total
      kidney content of both DNA and protein, and protein/DNA ratios returned to
      control values in whole kidney, inner cortex, and medulla. In contrast, in the
      kidneys of female rats, not only was overall growth response reduced, but neither
      total kidney protein content nor DNA content was increased. Increased protein/DNA
      ratios were seen in inner cortex and in outer and inner medulla, similar to that
      seen at day 3 in the kidneys of male rats. Neither baseline plasma (M-NP 793+/-10
      ng/ml, F-NP 704+/-32 ng/ml, p = NS) nor kidney IGF-I content (M-NP 520+/-55 ng/gm
      tissue, F-NP 506+/-54 ng/gm tissue, p = NS) differed between male and female rats
      fed NP diets. Both male and female rats showed a comparable increase in kidney
      IGF-I after 3 days of HP ingestion, and kidney IGF-I returned to control values
      by 14 days. There was no significant difference in the number or affinity of
      glomerular IGF-I receptors between male and female rats. In conclusion, we have
      shown that in the adult male rat, an increase in dietary protein ingestion
      results in a sustained increase in kidney size that is initially consistent with
      a hypertrophic response but subsequently shows elements of hyperplasia. In
      contrast, in the female rat, although there was evidence of the initial
      hypertrophic (and IGF-I) responses to increased dietary protein, the increase in
      kidney size was not sustained. However, these profound gender-based differences
      in the growth response to dietary protein did not appear to be due to differences
      in kidney expression of IGF-I or its receptors.

PMID- 9579391
TI  - Quantification of insulin in dried blood spots.
AB  - A method has been developed in which the concentrations of insulin in dried blood
      spots on filter paper can be estimated. The technique involves elution of blood
      from the paper, evaporation, and rehydration in assay buffer. The resuspended
      samples are then assayed by radioimmunoassay. The ratio of control plasma to
      control dried blood spot insulin values is used as a conversion factor for
      unknown samples on paper to express the dried blood spot insulin concentration in
      plasma equivalents. Intra-assay variability was 14%, and interassay variability
      was 25%, but the elution conversion factor had a variability of about 40% among
      individuals. This technique has substantial advantages for field studies, but
      elevated values should be confirmed by a venous plasma sample measurement in a
      conventional radioimmunoassay.

PMID- 9579392
TI  - Urinary trypsin inhibitor reduces the release of histamine from rat peritoneal
      mast cells.
AB  - We determined the ability of urinary trypsin inhibitor (UTI), which is a Kunitz
      type protease inhibitor present in serum and in urine, to inhibit rat peritoneal
      mast cell (RPMC) mediator release induced by several stimuli. UTI attenuated the
      immunoglobulin E-mediated release of both preformed (histamine) and newly formed
      (leukotriene C4) mediators from RPMCs. Inhibition (21%+/-5%) of the anti-IgE
      triggered release of histamine was observed after a 30-minute incubation of RPMCs
      with UTI (5 micromol/L). To investigate the specificity of the UTI effect, we
      studied the stimulatory activity of phorbol ester (phorbol 12-myristate 13
      acetate (PMA)) or calcium ionophore A23187 in control and UTI-treated mast cells.
      The efficacy of UTI as an inhibitor was dependent on the nature of the stimulus,
      because histamine release induced by PMA-mediated or calcium ionophore A23187
      mediated processes was not inhibited by UTI. A series of structurally distinct
      protease inhibitors did not inhibit IgE-induced release of mediators from RPMCs.
      The Kunitz-type protease inhibitors are important in the regulation of RPMC
      function. In parallel with the UTI-related decrease in anti-IgE stimulatory
      activity on mediator release, increased microviscosity of membrane lipids could
      be observed by two independent experiments on fluorescence polarization with
      diphenylhexatriene (DPH) and on the fluorescence probe fluorescein isothiocyanate
      concanavalin A. UTI reduces mediator release by a mechanism-possibly an
      interruption of the coupling of receptor and effector systems-because UTI acts as
      an agent to decrease biologic lipid membrane fluidity.

PMID- 9579393
TI  - Birth and fate of proliferative cells in the inner nuclear layer of the mature
      fish retina.
AB  - In teleost fish, unlike other vertebrates, the retina continues to grow
      throughout the animal's life both by stretching of the mature tissue and by the
      addition of new cells. Following larval development, new retinal cell birth is
      known to occur in a rim at the periphery of the mature retina and in the outer
      nuclear layer (ONL). We have now found that cell birth and proliferation also
      occurs in the inner nuclear layer (INL) of the mature fish retina. In rainbow
      trout (Onchoryncus mykiss), proliferative cells exist in the INL of fish of all
      ages, at least up to 2 years posthatching. The proliferative cells form clusters
      in the INL that align in radial columns, reaching from the inner to the outer
      plexiform layers. The density of proliferative cell clusters changes along the
      equatorial plane of the retina and is highest near both the nasal and temporal
      poles. Our data suggest that, after birth, the proliferative cells migrate away
      from the INL and into the ONL, with a half-time of about 3 days, and their cell
      bodies can be seen in the outer plexiform layer. Once they are in the ONL, the
      proliferative cells continue to divide and likely give rise to the precursor
      cells that differentiate into new rod photoreceptors.

PMID- 9579394
TI  - Early neuromeric distribution of tyrosine-hydroxylase-immunoreactive neurons in
      human embryos.
AB  - A segmental mapping of brain tyrosine-hydroxylase-immunoreactive (TH-IR) neurons
      in human embryos between 4.5 and 6 weeks of gestation locates with novel
      precision the dorsoventral and anteroposterior topography of the catecholamine
      synthetizing primordia relative to neuromeric units. The data support the
      following conclusions. (1) All transverse sectors of the brain (prosomeres in the
      forebrain, midbrain, rhombomeres in the hindbrain, spinal cord) produce TH-IR
      neuronal populations. (2) Each segment shows peculiarities in its contribution to
      the catecholamine system, but there are some overall regularities, which reflect
      that some TH-IR populations develop similarly in different segments. (3)
      Dorsoventral topology of the TH-IR neurons indicates that at least four separate
      longitudinal zones (in the floor and basal plates and twice in the alar plate)
      found across most segments are capable of producing the TH-IR phenotype. (4)
      Basal plate TH-IR neurons tend to migrate intrasegmentally to a ventrolateral
      superficial position, although some remain periventricular; those in the
      brainstem are related to motoneurons of the oculomotor and branchiomotor nuclei.
      (5) Some alar TH-IR populations migrate superficially within the segmental
      boundaries. (6) Most catecholaminergic anatomical entities are formed as fusions
      of smaller segmental components, each of which show similar histogenetic
      patterns. A nomenclature is proposed that partly adheres to previous terminology
      but introduces the distinction of embryologically different cell populations and
      unifies longitudinally analogous entities. Such a model, as presented in the
      present study, is convenient for resolving problems of homology of the
      catecholamine system across the diversity of vertebrate forms.

PMID- 9579395
TI  - Developmental changes in expression of myotonic dystrophy protein kinase in the
      rat central nervous system.
AB  - Myotonic dystrophy protein kinase (DMPK) is the protein product of the genetic
      locus associated with myotonic dystrophy, in which alterations of muscle
      excitability, cardiac conduction defects, mental retardation, and cognitive
      deficiencies are inherited as an autosomal dominant trait. DMPK belongs to a
      novel protein serine/threonine kinase family, but its regulation and
      physiological functions have not been specified. In a first step toward
      understanding the functions of DMPK in the central nervous system, we have
      characterized its localization and developmental pattern of expression in rat
      brain and spinal cord by using a monospecific rabbit antiserum produced against
      bacterially expressed DMPK. Expression of DMPK begins after birth and increases
      gradually to peak at postnatal day 21 with antibody labeling of neuronal cell
      types in many regions. After postnatal day 21 and proceeding to the adult, the
      pattern of expression becomes more restricted, with localization to certain
      regions or cell groups in the central nervous system. Electron microscopy reveals
      localization within adult spinal motor neurons to the endoplasmic reticulum and
      dendritic microtubules. The adult localizations suggest that DMPK may function in
      membrane trafficking and secretion within neurons associated with cognition,
      memory, and motor control.

PMID- 9579396
TI  - Evidence for an esophageal origin of VIP-IR and NO synthase-IR nerves innervating
      the guinea pig trachealis: a retrograde neuronal tracing and immunohistochemical
      analysis.
AB  - Nonadrenergic noncholinergic (NANC) relaxations of the guinea pig trachea are
      thought to be mediated by vasoactive intestinal peptide (VIP) and nitric oxide
      (NO). Physiological studies have indicated that the parasympathetic ganglion
      neurons mediating NANC relaxations of the guinea pig trachea but not the ganglion
      neurons mediating cholinergic contractions are in some way associated with the
      adjacent esophagus. In the present study, we attempted to locate precisely the
      noncholinergic parasympathetic ganglia innervating the trachealis. Two days after
      injection of the retrograde neuronal tracer DiI into the trachealis of
      organotypic cultures of the guinea pig trachea and esophagus, neurons within the
      myenteric plexus of the esophagus or closely associated with the outer striated
      longitudinal muscle layers of the esophagus were labeled. Subsequent
      immunohistochemical analyses revealed that a majority of the retrogradely labeled
      neurons possessed VIP immunoreactivity (IR) or NO synthase (NOS)-IR or had VIP-IR
      nerve fibers associated with their cell bodies. By contrast, no labeling of
      esophageal neurons was seen when the tissue between the trachea and esophagus had
      been disrupted by blunt dissection prior to tracer injection or when the cultures
      were treated with the axonal transport inhibitor colchicine. The results of these
      experiments provide the first direct evidence that VIP-IR and NOS-IR neurons
      intrinsic to the guinea pig esophagus project axons to the adjacent trachealis.
      Based on their location and phenotype and the results of our previous studies, it
      is likely that these neurons are the postganglionic parasympathetic neurons
      mediating NANC relaxations of the trachealis.

PMID- 9579397
TI  - Activity-regulated cell death contributes to the formation of ON and OFF alpha
      ganglion cell mosaics.
AB  - At maturity, ON and OFF alpha ganglion cells in the cat retina are arrayed in
      regular mosaics, with adjacent cells commonly forming ON-OFF pairs. In the
      present study, we investigated the role of activity-mediated ganglion cell death
      in the formation of such cellular patterns. Because direct measures of ganglion
      cell mosaics are problematic in the developing retina, we examined the
      distributions of ON and OFF alpha cells in the postnatal cat retina by assessing
      the degree to which cells in closest proximity were of opposite sign (i.e., ON
      OFF pairs). Computer simulations demonstrated that superimposition of two regular
      distributions results in a high incidence (approximately 90%) of opposite sign
      pairs. This is also the case for ON and OFF alpha cells in the mature retina,
      reflecting the high degree of regularity exhibited by this cell class. In
      contrast, during the first postnatal month, alpha cells displayed a much lower
      incidence of opposite sign pairs (approximately 60%), comparable to the
      superimposition of two simulated random distributions. We also show that there is
      a 20% loss of alpha cells in the central retina during postnatal development and
      that this magnitude of loss is sufficient to form regular distributions of ON and
      OFF cells. To assess the influence of sodium voltage-gated activity on this
      developmental process, intraocular injections of tetrodotoxin (TTX) were made
      during the postnatal period of alpha cell loss. When the TTX-treated animals
      reached maturity, there was a dose-related decrease in the incidence of opposite
      sign pairs, without any appreciable change in cell density. Moreover, the
      regularity index of ON and OFF cells was significantly lower than normal in the
      TTX-treated retinas. These findings demonstrate that a spatially selective
      pattern of ganglion cell loss contributes to the formation of regular ON and OFF
      ganglion cell distributions and that such cell loss is regulated by retinal
      activity.

PMID- 9579399
TI  - Topographical organization of group II afferent input in the rat spinal cord.
AB  - The organization of neurons in the lumbar enlargement of the rat spinal cord
      processing information conveyed by group II afferents of hind-limb muscle nerves
      has been investigated by using cord dorsum and intraspinal field potential
      recording. Group II afferents of different muscle nerves were found to evoke
      their strongest synaptic actions in specific segments of the lumbar cord. Group
      II afferents of quadriceps and deep peroneal nerves evoked potentials mainly at
      the rostral end of the lumbar enlargement (L1-rostral L3), whereas group II
      afferents of gastrocnemius-soleus and hamstring nerves evoked their main synaptic
      actions at the caudal end of the lumbar enlargement (L5). In the central lumbar
      segments (caudal L3-L4), the largest group II potentials were produced by
      afferents of tibialis posterior and, to a lesser degree, flexor digitorum longus.
      Field potentials evoked by group II afferents of quadriceps, tibialis posterior,
      and flexor digitorum longus were largest in the dorsal horn (up to 600 microV),
      but also occurred in the ventral horn where they were sometimes preceded by group
      I field potentials. In contrast, field potentials evoked by group II afferents of
      gastrocnemius-soleus and hamstring nerves were restricted to the dorsal horn.
      These results indicate that neurons in different segments of the rat lumbar
      spinal cord process information from group II afferents of different hind-limb
      muscles. Furthermore, the topographical organization of group II neuronal systems
      in the rat is similar in several respects to that in the cat and may therefore
      represent a general organizational feature of the mammalian spinal cord.

PMID- 9579398
TI  - Regional and cellular distribution of low affinity neurotensin receptor mRNA in
      adult and developing mouse brain.
AB  - Levocabastine-sensitive neurotensin receptor (NTRL) mRNAs were localized by in
      situ hybridization in adult and developing mouse brain. NTRL hybridization signal
      was widely distributed throughout the neuraxis. The highest concentrations of
      NTRL mRNA were detected in the olfactory system, olfactory tubercle, cerebral and
      cerebellar cortices, hippocampal formation, and selective hypothalamic nuclei.
      Moderate to dense hybridization signal was also observed in association with a
      variety of auditory, visual, and somatosensory relay nuclei, suggesting that the
      NTRL might be involved in a widespread modulation of primary afferent pathways.
      Finally a high expression of NTRL was evident in brainstem structures implicated
      in descending antinociceptive influences (e.g., the periaqueductal gray, nucleus
      raphe magnus, gigantocellular reticular nucleus, pars alpha, and lateral
      paragigantocellular nucleus) consistent with the proposed mediation of NT-induced
      analgesia by the NTRL. Although most of the regions found here to express NTRL
      mRNA were previously reported to be devoid of mRNA encoding the high affinity NT
      receptor (NTRH), a few areas (e.g., the anterior olfactory nucleus, medial
      septum, diagonal band of Broca, reticular thalamic nucleus, suprachiasmatic
      hypothalamic nucleus, and pontine nucleus) were enriched in both receptor
      subtypes, suggesting a possible coexpression of these receptors by the same
      cells. Ontogenic studies revealed that in the mouse brain, NTRL mRNA was detected
      only from postnatal day 14 and did not reach adulthood concentrations before day
      30. In cerebral cortex, the developmental increase in NTRL expression was
      correlated over time with the decrease in NTRH expression previously documented
      in the rat, suggesting a progressive takeover of the latter by the former for
      transduction of the effects of NT in this structure.

PMID- 9579400
TI  - Transient, high levels of SNAP-25 expression in cholinergic amacrine cells during
      postnatal development of the mammalian retina.
AB  - In the present study, we have examined the development of cholinergic amacrine
      cells in the retina of the Brazilian opossum, Monodelphis domestica. An antibody
      directed against choline acetyltransferase (ChAT) revealed that ChAT-like
      immunoreactivity (ChAT-IR) was first observed at 15 days postnatal (15PN). By
      25PN, ChAT-IR identified two matching populations of amacrine cells in the inner
      nuclear and ganglion cell layer. Bromodeoxyuridine birth-dating analysis coupled
      with immunolabeling with the anti-ChAT antibody revealed that the cholinergic
      amacrine cells are born postnatally, between 2PN and 15PN. In addition, we have
      examined the differentiation of the cholinergic amacrine cells by using an
      antibody directed against a presynaptic terminal-associated protein, synaptosomal
      associated protein of 25 kDa (SNAP-25). Double-labeling analysis revealed that
      relatively high levels of SNAP-25-IR were selectively present in cholinergic
      amacrine cells prior to eye opening. However, in the mature retina, high levels
      of SNAP-25-IR were no longer observed in the ChAT-IR amacrine cells. These
      results reveal a distinct period in development, prior to eye opening, when high
      levels of SNAP-25-IR are selectively expressed in cholinergic amacrine cells. The
      specificity and time course of the high levels of SNAP-25 in cholinergic amacrine
      cells may be critical in mediating the transient properties of these cells during
      visual system development.

PMID- 9579401
TI  - Insulin-related growth factors stimulate proliferation of retinal progenitors in
      the goldfish.
AB  - The retina of the adult goldfish grows throughout the life of the animal, in
      part, by the continual addition of new neurons. Further, destruction of extant
      neurons in this tissue stimulates neuronal regeneration. In an attempt to
      identify growth factors that regulate both normal and injury-stimulated
      neurogenesis, we used organ culture techniques and tested nine peptide growth
      factors for their ability to modulate cell proliferation in both normal retinas
      and retinas with lesions. Of the growth factors tested, only the insulin-related
      peptides (insulin and insulin-like growth factors I and II) consistently
      stimulated proliferation, and this was restricted to the retinal progenitors
      within the circumferential germinal zone. None of the growth factors tested
      stimulated proliferation of rod precursors (cells in the mature retina whose
      progeny are exclusively rod photoreceptors) or the injury-stimulated retinal
      progenitors. Although the negative data are subject to multiple interpretations,
      these data suggest that in the retina of the adult goldfish, insulin-related
      peptides regulate proliferation of retinal progenitors within the circumferential
      germinal zone, but molecules that modulate the proliferation of the rod
      precursors or injury-induced retinal progenitors in the retina of the adult
      goldfish have yet to be identified.

PMID- 9579402
TI  - Insulin-like growth factor-I binds in the inner plexiform layer and
      circumferential germinal zone in the retina of the goldfish.
AB  - Results of the previous study suggest that insulin-related peptides regulate
      proliferation of retinal progenitors in the adult goldfish. Because of their
      known roles in retinal neurogenesis, we have chosen to focus future studies on
      insulin-like growth factor I (IGF-I) and the IGF-I receptor. In the study
      described here, we characterized the spatial distribution and specificity of IGF
      I binding sites in the retina of the adult goldfish by performing receptor
      binding autoradiography with [125I]-IGF-I alone and with unlabeled IGF-I-related
      molecules (IGF-I, IGF-II, insulin, and des-[1-3]-IGF-I) as competitive inhibitors
      of [125I]-IGF-I binding. The results of these experiments show that IGF-I binds
      in two locations in the retina of the adult goldfish, within the inner plexiform
      layer of the differentiated retina and the circumferential germinal zone. The
      competition experiments suggest that [125I]-IGF-I binds at sites specific for IGF
      I, and that both IGF-I receptors and IGF-I binding proteins are present in the
      retina.

PMID- 9579403
TI  - Mechanisms of docosahexaenoic acid accretion in the fetal brain.
AB  - Docosahexaenoic acid (DHA, 22:6 n-3) is the major polyunsaturated fatty acid
      (PUFA) in the adult mammalian brain. DHA is an essential fatty acid (FA) since
      it, or its short chain precursor, alpha-linolenic acid (LnA, 18:3 n-3), have to
      be obtained in the diet. Moreover, dietary n-3 FA deficiency is associated with
      biochemical changes in the brain and with disturbances in vision and other
      neurological parameters. Under normal nutritional conditions, fetal brain DHA
      accumulation is substantial, with a "DHA accretion spurt" being demonstrated in
      the last period of gestation. This accumulation is supported by the maternal
      supply of DHA or LnA, but selectivity of DHA accumulation is probably a placental
      function whose mechanism is lately being clarified. The fetal gastrointestinal (G
      I) tract may be instrumental in supplying DHA to the fetal brain under certain
      conditions, such as following intra-amniotic administration of ethyl
      docosahexaenoate (Et-DHA). In this pathway, DHA is supplied independently of the
      maternal metabolism, and the fetal liver is apparently involved. The fetal G-I
      tract may be advantageous for DHA supply in cases of maternal-placental
      insufficiency resulting in intrauterine growth retardation. The fetal brain
      itself is capable of metabolizing LnA to DHA, without the participation of the
      fetal liver, thus contributing to the accumulation of its own DHA during one of
      the most crucial periods of its development.

PMID- 9579404
TI  - Antibody-mediated oligodendrocyte cell death requires an astrocyte-derived
      cosignal.
AB  - We have described a monoclonal antibody (mAb), 2B10, that identifies a cell
      surface protein expressed only on oligodendrocytes, the myelin-forming cells in
      the vertebrate central nervous system. To examine the effect of mAb 2B10 on
      oligodendrocyte development and survival, purified antibody was added to
      dissociated cultures of neonatal rat spinal cord. Addition of mAb 2B10 induced
      significant cell death, with a reduction of approximately 70% in the number of
      differentiated oligodendrocytes. The number of astrocytes was unaltered. Addition
      of mAb 2B10 did not affect the proliferation or differentiation of
      oligodendrocyte precursors. MAb 2B10-induced death of differentiated
      oligodendrocytes was independent of complement but did require an environmental
      signal. In purified oligodendrocyte cultures, binding of the antibody to
      oligodendrocytes did not induce cell death. Conditioned medium and transwell
      coculture experiments indicated that the required environmental signals were not
      soluble. By contrast, when oligodendrocytes were cocultured with astrocytes,
      addition of mAb 2B10 specifically induced cell death of differentiated
      oligodendrocytes, suggesting that a locally acting cosignal from astrocytes was
      required to facilitate the cell death. This cosignal was provided by live
      astrocytes but not by fixed astrocytes, microglia, or fibroblasts. Such antibody
      induced oligodendrocyte cell death may explain in part the loss of myelin-forming
      cells in demyelination conditions, such as multiple sclerosis.

PMID- 9579405
TI  - BDNF induction of tryptophan hydroxylase mRNA levels in the rat brain.
AB  - We have previously demonstrated an augmentation of serotonergic activity within
      various brain areas following infusion of brain-derived neurotrophic factor
      (BDNF) into the midbrain near the periaqueductal gray and dorsal and median raphe
      nuclei (PAG/DR). However, the mechanism of this BDNF-induced modulatory effect on
      serotonergic systems was unclear. The aim of the present work was to study the
      regulation of tryptophan hydroxylase (TPH) mRNA levels after chronic BDNF
      administration in vivo. TPH mRNA levels were measured using a quantitative
      competitive reverse transcription polymerase chain reaction (RT-PCR) assay. A
      significant increase in the expression of TPH mRNA (13-fold) was found within the
      PAG/DR as early as 24 hr after onset of BDNF infusion and was sustained
      throughout the duration of infusion (11 days). This was accompanied by increased
      serotonin (5-hydroxytryptamine, 5-HT) levels and decreased nociceptive
      responsiveness assessed by tail-flick latency. BDNF induction of TPH mRNA levels
      was also observed in a serotonergic cell line derived from raphe neurons,
      indicating that BDNF can directly regulate TPH mRNA levels. These results suggest
      that BDNF augments 5-HT synthesis in vivo by directly enhancing steady-state TPH
      mRNA levels, and subsequently leading to marked behavioral alterations.

PMID- 9579406
TI  - Effects of mutation of the Olf-1 motif on transgene expression in olfactory
      receptor neurons.
AB  - We have examined the effect of mutating the Olf-1 binding motif of the olfactory
      marker protein (OMP) promoter in determining olfactory neuron-specific gene
      expression in adult tissues and during embryonic development. The proximal Olf-1
      motif located 170 nucleotides upstream of the transcription start site of the OMP
      gene was mutated to prevent its interaction with the Olf-1 factor in vitro. The
      wild-type and mutated fragments of the OMP gene extending from -239 to +55
      nucleotides relative to the transcription start site were used to direct
      expression of a lacZ reporter gene in transgenic mice. The transgenic animals
      were analyzed for cell-specific and developmental expression of the reporter
      gene. We demonstrate that the mutation that prevents interaction of Olf-1 with
      its binding site does not alter the temporal and spatial patterns of gene
      expression in olfactory sensory neurons but does alter the specificity and level
      of expression in other neuronal populations. These observations are consistent
      with our demonstration that the mutated Olf-1 site interacts with nuclear
      proteins present in the central nervous system (CNS).

PMID- 9579407
TI  - Metabolic labeling of a subset of glial cells by UDP-galactose: implication for
      astrocyte lineage diversity.
AB  - Astrocytes are implicated in many aspects of brain function; however, it remains
      unclear whether astrocytes arise from a single cell lineage. It is therefore
      important to obtain new markers for the astrocyte cell lineage. We show that
      exogenously added UDP-galactose (UDP-Gal) can be used to metabolically label a
      subset of glial fibrillary acidic protein-positive (GFAP+) cells. UDP-Gal was
      incorporated into the cultured embryonic mouse brain slices in a time-dependent
      manner. Surprisingly, the transferred sugar moiety was no longer Gal but was
      mainly glucose. Most of the radioactivity was transferred to a polymer of
      glucose, most likely to be glycogen, and also to glucosyl ceramide. In the slice
      culture, the reaction products were distributed densely in the ventricular zone
      and also on process-like structures extending to the pial surface. In
      dissociation culture, UDP-Gal labeled some of the GFAP+ cells and some of the
      vimentin+ cells. Because radial glial cells (RGCs) contain glycogen and change
      from vimentin+ to GFAP+, it is strongly suggested that UDP-Gal labeled RGCs and
      their descendants. Only 27% of the GFAP+ cells were labeled with UDP-Gal, which
      suggests that only a subset of astrocytes are derived from RGCs and that there is
      a discrete group of GFAP+ cells that is not generated from RGCs.

PMID- 9579408
TI  - alpha-Tocopherol protects PC12 cells from hyperoxia-induced apoptosis.
AB  - A rat clonal pheochromocytoma cell line (PC12) was cultured under normoxic (21%
      O2) and hyperoxic (50% O2) conditions. PC12 cells underwent apoptotic cell death
      when they were cultured in charcoal-stripped medium in a high-oxygen atmosphere.
      Vitamin E homologs, alpha-tocopherol (alphaT), beta-tocopherol (betaT), gamma
      tocopherol (gammaT), and delta-tocopherol (deltaT), were added to the culture
      medium to study their biological activities. AlphaT was more effective than
      gammaT and deltaT in preventing hyperoxia-induced cell death. Addition of
      exogenous alphaT to charcoal-treated medium prevented lactate dehydrogenase (LDH)
      leakage from PC12 cells and also inhibited the apoptosis, which was accompanied
      by DNA fragmentation. Additional alphaT was rapidly concentrated in PC12 cells,
      suggesting that it exerts antioxidant effects. Our data show that PC12 cell death
      under high-oxygen conditions is due to apoptosis and that, among the vitamin E
      homologs, alphaT most effectively prevents hyperoxic apoptosis.

PMID- 9579410
TI  - Social environment alters both ontogeny of dopamine innervation of the medial
      prefrontal cortex and maturation of working memory in gerbils (Meriones
      unguiculatus).
AB  - Male gerbils (Meriones unguiculatus) were bred and reared either grouped under
      enriched environmental conditions or isolated under impoverished environmental
      conditions. The objective of the present study was to examine the influence of
      social environment on structural and functional ontogeny of the medial prefrontal
      cortex (mPFC). In this respect, we investigated the maturation of both prefrontal
      dopamine (DA) innervation and working memory. For that purpose, at the age of
      postnatal day 90, prefrontal DA fibers were stained immunocytochemically using an
      antibody against glutaraldehyde-conjugated DA and innervation density was
      determined by means of a computer controlled program for image analysis. In order
      to evaluate environmental effects on working memory, 90-day-old gerbils were
      tested for y-maze delayed alternation. It was found that, isolation produced a
      significant and severe restraint of the maturation of prefrontal DA innervation,
      leading to fiber densities which were 56% below those in group-reared gerbils.
      Isolation also induced a significant impairment of delayed alternation
      performance on the y-maze indicating that obvious deficits in working memory had
      developed under restricted rearing conditions. The present results are discussed
      with regard to activity-dependent postnatal maturation of the cortex and adaptive
      neuroplasticity.

PMID- 9579409
TI  - Activation of phosphatidylinositol 3-kinase by brain-derived neurotrophic factor
      gene transfection in septo-hippocampal cultures.
AB  - Brain-derived neurotrophic factor (BDNF) has therapeutic potential for treatment
      of the injured central nervous system. BDNF induces both differentiation and
      survival of neurons by binding to trkB receptors. This interaction stimulates the
      intrinsic tyrosine kinase activity of trkB, initiating a signal cascade involving
      the phosphorylation of intracellular protein on tyrosine, serine, and threonine
      residues. The purpose of this investigation was to examine the effects of
      cationic lipid-mediated gene transfection of BDNF on phosphatidylinositol 3 (PI3)
      kinase activity in primary septo-hippocampal cell cultures. Thirty-six hours
      after BDNF gene transfection in the primary CNS cell culture, PI3-kinase activity
      was significantly increased. The increased PI3-kinase activity was inhibited by
      wortmannin, a selective and irreversible inhibitor of PI3-kinase. In addition,
      wortmannin blocked neurofilament increases induced by BDNF gene transfection.
      This result suggests a possible role of PI3-kinase activation in neuroprotective
      effects produced by BDNF gene transfection.

PMID- 9579411
TI  - Vitamin D receptor stable transfection restores the susceptibility to 1,25
      dihydroxyvitamin D3 cytotoxicity in a rat glioma resistant clone.
AB  - Recently, 1,25-dihydroxyvitamin D3 (1,25-D3) and less hypercalcemic analogs were
      shown to exert a delayed cytotoxic effect on rat C6 glioma cells. 1,25-D3 induces
      in these cells a programmed cell death, accompanied by the induction of c-myc,
      p53 and gadd 45 genes. The involvement of the intracellular vitamin D receptor
      (VDR) remained to be determined. In this lethal process, we have investigated its
      role in a subclone of C6 cells, which was isolated on the basis of its resistance
      to 1,25-D3, and in which VDR expression was not detected either at the mRNA or
      protein levels. The stable transfection of a rat VDR cDNA into this clone
      restored its susceptibility to the cytotoxic effects of 1,25-D3. This phenomenon
      was accompanied by a dramatic upregulation of c-myc mRNA expression, as already
      described in a C6-sensitive clone. These results provide the first evidence that
      VDR expression, if not sufficient, is necessary to mediate 1,25-D3 cytotoxic
      effect in C6 glioma cells. Since VDR mRNA expression has been already reported in
      human brain tumors, our data imply that the identification of VDR expression
      could become a prerequisite in any strategy of glioma treatment with vitamin D
      analogs.

PMID- 9579412
TI  - Dynamic mechanical deformation of neurons triggers an acute calcium response and
      cell injury involving the N-methyl-D-aspartate glutamate receptor.
AB  - A biomechanical in vitro model of traumatic brain injury was used to examine
      cellular response to physical insults and the underlying mechanisms that lead to
      cell dysfunction. A cell shearing injury device was used to deform human NTera-2
      neurons at high loading rates during the investigation of mechanisms of cytosolic
      free calcium increases, which may be detrimental to a cell. Cytosolic free
      calcium rose immediately to almost three times baseline and was associated with
      lactate dehydrogenase release at 24 hr, indicating significant cell injury. Low
      loading rates did not elicit these responses. A major portion of the calcium
      increase and subsequent cell injury was dependent on the presence of
      extracellular free calcium. Blocking the N-methyl-D-aspartate glutamate receptor
      complex with dizocilipine maleate attenuated calcium increases by 45% in injured
      neurons and blocked a significant part (50%) of the lactate dehydrogenase
      release. In addition, pretreatment with nifedipine or riluzole also significantly
      reduced cytosolic free calcium but did not affect cell injury, whereas
      tetrodotoxin had no affect on either outcome parameter. These results suggest
      that the increased membrane permeability and immediate calcium influx associated
      with this model of mechanical injury trigger several cellular pathways, including
      N-methyl-D-aspartate receptor-mediated cell damage.

PMID- 9579413
TI  - Developing and mature oligodendrocytes respond differently to the immune cytokine
      interferon-gamma.
AB  - Increasing evidence suggests that the immune cytokine interferon-gamma (IFN
      gamma) plays a deleterious role in immune-mediated demyelinating disorders. To
      further understand the effects of IFN-gamma on oligodendrocytes, we have compared
      and quantitated the response of developing and mature oligodendrocytes in vitro
      to IFN-gamma and have observed several differences. Morphological changes and
      cell death occurred in developing cultures after 2 days in IFN-gamma, and in
      mature oligodendrocytes after 4-7 days. Developing oligodendrocytes underwent
      significantly increased apoptotic cell death in the presence of IFN-gamma, but
      mature oligodendrocytes exposed to IFN-gamma died of necrosis. Prior to
      morphological changes or cell death in mature oligodendrocytes exposed to IFN
      gamma, steady-state levels of myelin-specific mRNAs and proteins were reduced.
      Thus, these results indicate that the sensitivity of oligodendrocytes to IFN
      gamma is related to the developmental state of the cell. Such information is
      crucial for understanding the response of oligodendrocytes in immune-mediated
      demyelinating disorders and during remyelination in these diseases.

PMID- 9579415
TI  - History, structure, and function of the Internet.
AB  - The Internet stands at the forefront of telecommunications in medicine. This
      worldwide system of computers had its beginnings in networking projects in the
      United States and western Europe in the 1960s and 1970s. The precursor of the
      Internet was ARPANET, a long-distance telecommunication network funded by the
      Department of Defense that linked together computers throughout the United
      States. In the 1980s, ARPANET was superseded by NSFNET, a series of networks
      created by the National Science Foundation, which established the present-day
      structure of the Internet. The physical structure of the Internet resembles and
      is integrated with the telephone system. Long-distance data transport services
      are provided by large telecommunication companies, called network service
      providers (NSPs), through high-capacity, high-speed national and international
      fiber optic cables. These transport services are accessed through Internet
      service providers, ISPs. ISPs, the equivalent of regional Bell operating
      companies, provide the physical link to the NSPs for individuals and
      organizations. Telecommunications on the Internet are standardized by a set of
      communications protocols, the TCP/IP protocol suite, that describe routing of
      messages over the Internet, computer naming conventions, and commonly used
      Internet services such as e-mail. At present, the Internet consists of over 20
      million computer worldwide and is continuing to grow at a rapid rate. Along with
      the growth of the Internet, higher speed access methods are offering a range of
      new services such as real-time video and voice communications. Medical education,
      teaching, and research, as well as clinical practice, will be affected in
      numerous different ways by these advances.

PMID- 9579414
TI  - Increased neuronal cell survival after L-deprenyl treatment in experimental
      thiamine deficiency.
AB  - Experimental thiamine deficiency results in a reproducible pattern of selective
      neuronal cell death. Events such as blood-brain barrier breakdown, N-methyl-D
      aspartic acid (NMDA) receptor-mediated excitotoxicity, and increased reactive
      oxygen species have been implicated in thiamine deficiency-induced neural loss. L
      deprenyl protects dopaminergic, noradrenergic, and acetylcholinergic neurons from
      neurotoxic, mechanical, and excitotoxic damage. In the present study, the effects
      of l-deprenyl on neuronal cell survival were examined in rats made thiamine
      deficient by daily administration of the central thiamine antagonist pyrithiamine
      (0.5 mg/kg s.c.). Rats assigned to thiamine deficient or control groups received
      daily injections of l-deprenyl (0.25, 0.5, or 1.0 mg/kg/day i.p.) or vehicle
      until they reached a state of severe thiamine deficiency (loss of righting
      reflex). At this stage, thiamine status was restored by daily injections of
      thiamine (10 mg/kg s.c.) for 3 days, after which the animals were killed, and
      their brains were processed for neuronal cell counts (cresyl violet staining),
      astrocytic proliferation [glial fibrillary acidic protein (GFAP)
      immunohistochemistry], and monoamine oxidase B (MAO-B) activity. All rats
      receiving l-deprenyl (all doses) had significantly decreased neuronal cell loss
      in thalamic nuclei, in the inferior colliculus, and in the inferior olive and had
      a concomitant decrease in reactive astrocytic proliferation compared with the
      thiamine-deficient, vehicle-treated rats. The neuroprotective effects of l
      deprenyl in thiamine deficiency induced brain damage most likely result from its
      properties other than its effects as an MAO-B inhibitor.

PMID- 9579416
TI  - Telemedicine in practice.
AB  - Telemedicine is defined as the "delivery of health care and sharing of medical
      knowledge over a distance using telecommunication systems." The concept of
      telemedicine is not new. Beyond the use of the telephone, there were numerous
      attempts to develop telemedicine programs in the 1960s mostly based on
      interactive television. The early experience was conceptionally encouraging but
      suffered inadequate technology. With a few notable exceptions such as the
      telemetry of medical data in the space program, there was very little advancement
      of telemedicine in the 1970s and 1980s. Interest in telemedicine has exploded in
      the 1990s with the development of medical devices suited to capturing images and
      other data in digital electronic form and the development and installation of
      high speed, high bandwidth telecommunication systems around the world. Clinical
      applications of telemedicine are now found in virtually every specialty.
      Teleradiology is the most common application followed by cardiology, dermatology,
      psychiatry, emergency medicine, home health care, pathology, and oncology. The
      technological basis and the practical issues are highly variable from one
      clinical application to another. Teleradiology, including telenuclear medicine,
      is one of the more well-defined telemedicine services. Techniques have been
      developed for the acquisition and digitization of images, image compression,
      image transmission, and image interpretation. The American College of Radiology
      has promulgated standards for teleradiology, including the requirement for the
      use of high resolution 2000 x 2000 pixel workstations for the interpretation of
      plain films. Other elements of the standard address image annotation, patient
      confidentiality, workstation functionality, cathode ray tube brightness, and
      image compression. Teleradiology systems are now widely deployed in clinical
      practice. Applications include providing service from larger to smaller
      institutions, coverage of outpatient clinics, imaging centers, and nursing homes.
      Teleradiology is also being used in international applications. Unresolved issues
      in telemedicine include licensure, the development of standards, reimbursement
      for services, patient confidentiality, and telecommunications infrastructure and
      cost. A number of states and medical boards have instituted policies and
      regulations to prevent physicians who are not licensed in the respective state to
      provide telemedicine services. This is a major impediment to the delivery of
      telemedicine between states. Telemedicine, including teleradiology, is here to
      stay and is changing the practice of medicine dramatically. National and
      international communications networks are being created that enable the sharing
      of information and knowledge at a distance. Technological barriers are being
      overcome leaving organizational, legal, financial, and special interest issues as
      the major impediments to the further development of telemedicine and realization
      of its benefits.

PMID- 9579417
TI  - Nuclear medicine data communications.
AB  - Nuclear Medicine was one of the earliest imaging modalities to adopt the use of
      computers for acquisition, processing, storage, and display of digital images.
      Originally used for processing images, computer technologies were quickly adopted
      for image storage, display, and transmission. Modern nuclear medicine cameras
      produce digital images that can be transmitted over computer networks to other
      cameras, storage devices, workstations, and printers. In order to achieve nuclear
      medicine data communication, images must be successfully acquired and transmitted
      to the appropriate location to be displayed or printed. Standards have been
      developed over the years to facilitate the creation of interfaces between vendors
      and equipment, notably the interfile format for nuclear medicine and the DICOM
      standard for medical images. Studies can be transmitted over network
      communication links to other sites using telecommunication protocol standards
      where they can be stored and/or displayed on a wide variety of devices. This
      ability to move images in a well-understood format to general purpose devices
      using standard equipment enables the use of the Internet to disseminate nuclear
      medicine study information over a wide area for clinical use, research, and
      education. A number of universities have created Internet sites with nuclear
      medicine teaching files and information. As technology advances, it will be
      feasible to transmit medical images of all kinds to virtually anyone who needs
      them in near real-time, without regard to the distance between locations, or the
      types of instrumentation and computers used. The next few years should prove to
      be very interesting for digital medical imaging in general and nuclear medicine
      in particular.

PMID- 9579418
TI  - Use of the Internet for teaching in nuclear medicine.
AB  - The Internet provides several new capabilities for education in nuclear medicine,
      including learning at a distance, facilitation of collaboration, increased
      availability of training resources, and ability to develop interactive teaching
      materials. Dedicated case-authoring software aided development of digital
      teaching files at the Mallinckrodt Institute of Radiology and the Joint Program
      in Nuclear Medicine. Accesses to these two teaching files from sites around the
      world have grown rapidly. Improvements in the speed of the Internet will allow
      inclusion of more images at higher resolution and more extensive use of cine.
      Development of server-based software will allow simulation of the actual image
      reading environment. A better understanding of how to use this new media will
      spur continued expansion in use of the Internet for nuclear medical education.

PMID- 9579419
TI  - Bioinformatics: searching the Net.
AB  - During the past 30 years, there has been an explosion in the volume of published
      medical information. As this volume has increased, so has the need for efficient
      methods for searching the data. MEDLINE, the primary medical database, is
      currently limited to abstracts of the medical literature. MEDLINE searches use
      AND/OR/NOT logical searching for keywords that have been assigned to each article
      and for textwords included in article abstracts. Recently, the complete text of
      some scientific journals, including figures and tables, has become accessible
      electronically. Keyword and textword searches can provide an overwhelming number
      of results. Search engines that use phrase searching, or searches that limit the
      number of words between two finds, improve the precision of search engines. The
      development of the Internet as a vehicle for worldwide communication, and the
      emergence of the World Wide Web (WWW) as a common vehicle for communication have
      made instantaneous access to much of the entire body of medical information an
      exciting possibility. There is more than one way to search the WWW for
      information. At the present time, two broad strategies have emerged for
      cataloging the WWW: directories and search engines. These allow more efficient
      searching of the WWW. Directories catalog WWW information by creating categories
      and subcategories of information and then publishing pointers to information
      within the category listings. Directories are analogous to yellow pages of the
      phone book. Search engines make no attempt to categorize information. They
      automatically scour the WWW looking for words and then automatically create an
      index of those words. When a specific search engine is used, its index is
      searched for a particular word. Usually, search engines are nonspecific and
      produce voluminous results. Use of AND/OR/NOT and "near" and "adjacent" search
      refinements greatly improve the results of a search. Search engines that limit
      their scope to specific sites, and metasearch sites that use multiple search
      engines optimized for specific types of searches have recently emerged. The
      distinctions between search engines and directory searches have blurred.
      Eventually, conceptual searching in which the computer searches for related
      ideas, without having to be given all the related keywords, may become a reality.
      This will free the user from having to learn specific rules about searching,
      allowing energies to be focused on results of the search, not the search itself.

PMID- 9579420
TI  - Nonvisualization of spleen on sulfur colloid images: a sequel of massive
      infarction.

PMID- 9579421
TI  - Bilateral perfusion defect/hypoperfusion in temporal and parietal regions on
      brain SPECT.

PMID- 9579422
TI  - Septal reverse redistribution on TI-201 chloride myocardial SPECT in left
      internal mammary artery bypass graft.

PMID- 9579423
TI  - Primary large cell neuroendocrine carcinoma: a cause of extracardiac uptake site
      of Tc99m tetrofosmin.

PMID- 9579424
TI  - Integrity and common sense in medicine.

PMID- 9579425
TI  - Field cancerization: why late "recurrent" ovarian cancer is not recurrent.
AB  - OBJECTIVE: Late "recurrence" of ovarian cancer may result from either regrowth of
      dormant tumor cells or from development of a new cancer caused by the phenomenon
      of field cancerization. Clinically, some recurrent ovarian cancers show the same
      therapeutic sensitivities to chemotherapy and surgery as did the primary disease,
      whereas others are refractory to all therapy. We hypothesize that recurrent
      ovarian cancers are distinguishable on the basis of a molecular genetic
      fingerprint and that some are actually new primary cancers of the peritoneum
      rather than recurrent ovarian cancer. STUDY DESIGN: We constructed molecular
      genetic fingerprints of 13 paired primary and late recurrent ovarian cancers to
      study their clonal relationships. The tumor pairs were analyzed for p53 mutations
      and allelotypes, patterns of X-chromosome inactivation, loss of heterozygosity,
      and microsatellite instability at 12 different loci on 6 different chromosomes.
      Techniques used included single-strand conformational polymorphism mutation
      screening and polymerase chain reaction-based sequence analysis of the p53 locus,
      restriction digestion of the androgen receptor locus to determine X-chromosome
      inactivation, and polyacrylamide gel electrophoresis of highly polymorphic
      dinucleotide, trinucleotide, and tetranucleotide repeats. RESULTS: The average
      age at initial diagnosis for this cohort was 54.7 years (range 45.3 to 65.5).
      Mean interval to recurrence was 42.7 months (range 28 to 62). Molecular
      fingerprints were characterized for 4 to 8 informative loci per tumor pair. The
      fingerprints of 10 (77%) differed significantly, strongly suggesting that a
      second primary cancer had developed. The remaining 3 tumor pairs demonstrated
      identical allelotypes consistent with regrowth of dormant tumor cells.
      CONCLUSION: Our results are consistent with the "field cancerization" hypothesis
      of ovarian carcinogenesis but could also be explained by a polyclonal tumor
      origin, which contrasts with the currently accepted monoclonal theory of ovarian
      carcinogenesis. Late development of a new primary cancer may herald the proband
      as a member of a familial cancer phenotype. These studies provide a molecular
      genetic rationale that both explains and prognosticates the clinical course of
      recurrent ovarian cancer.

PMID- 9579426
TI  - Evidence for a neutrophil-interleukin-8 system in human folliculogenesis.
AB  - OBJECTIVE: This study was conducted to determine whether polymorphonuclear
      leukocytes (neutrophils) and the potent chemoattractant interleukin-8 are
      associated with follicle development in the normal human ovary. STUDY DESIGN: We
      performed a morphometric analysis of neutrophils in 268 human ovarian follicles,
      of which 199 were preantral and 69 were antral. In each antral follicle the
      numbers of mitotic, apoptotic, and total granulosa cells were counted to
      determine healthy and atretic follicles. Interleukin-8 protein and messenger
      ribonucleic acid were detected by immunohistochemistry and in situ hybridization,
      respectively. RESULTS: Antral follicles contained relatively large numbers of
      neutrophils within the theca vasculature. The density of neutrophil was twofold
      greater (p < 0.05) in atretic versus healthy follicles. The neutrophil index
      (neutrophils/granulosa cells x 1000) was inversely correlated to the number of
      granulosa cells per follicle. Immunoreactive interleukin-8 was detected in the
      theca and granulosa cells of most all antral follicles examined. Interleukin-8
      messenger ribonucleic acid was demonstrated in theca and granulosa cells of some
      but not all follicles examined. CONCLUSIONS: Neutrophils are present in the theca
      of developing antral follicles, increase in number during atresia, and are
      associated with expression of interleukin-8 in the follicle wall.

PMID- 9579427
TI  - Impaired growth and risk of fetal death: is the tenth percentile the appropriate
      standard?
AB  - OBJECTIVE: Our purpose was to determine whether the 10th percentile of birth
      weight for gestational age is appropriate to identify fetuses at risk of death
      associated with impaired growth. STUDY DESIGN: All live births recorded in
      Virginia from Jan. 1, 1991, through Dec. 31, 1993, were examined. Percentile
      growth curves were constructed, and fetal, neonatal, and perinatal mortality
      rates were calculated for births within various percentile intervals. RESULTS:
      Significantly elevated fetal mortality was found for birth weights through the
      15th percentile. The odds ratio for fetal mortality relative to the baseline for
      births < or = 5th percentile was 5.6, for the 5th through the 10th percentile
      2.8, and for the 10th through the 15th percentile 1.9. These were all
      significant. CONCLUSION: Fetuses with birth weights between the 10th and 15th
      percentiles are at a significantly increased risk for fetal death. Therefore the
      use of the 15th percentile as a diagnostic threshold for the identification of
      the fetus at increased risk associated with impaired growth is recommended.

PMID- 9579428
TI  - BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an
      unselected ovarian cancer population: relationship to family history and
      implications for genetic testing.
AB  - OBJECTIVE: Our purpose was to determine the prevalence of BRCA1, BRCA2, and
      hereditary nonpolyposis colorectal cancer gene mutations in a large, unselected
      population of ovarian cancer patients and to evaluate the relationship between
      mutation status and a routinely obtained family history of cancer. STUDY DESIGN:
      One hundred sixteen consecutive ovarian cancer patients seen for routine clinical
      care were examined for BRCA1, BRCA2, hMSH2, and hMLH1 gene mutations with use of
      the polymerase chain reaction, single-strand conformation polymorphism analysis,
      and direct gene sequencing. Fisher's exact test was used to evaluate possible
      associations between BRCA1 and BRCA2 mutation status and specific familial
      characteristics. RESULTS: Among 116 unselected ovarian cancer patients we
      identified a total of 13 germline mutations in 12 patients: 10 in BRCA1, one each
      in hMSH2 and hMLH1, and a single BRCA2 mutation, which occurred in a patient also
      carrying a BRCA1 mutation. More than half the patients with BRCA1 mutations had
      family histories that would generally be considered unremarkable. Of 22 family
      history variables analyzed, only two (maternal family history of breast or
      ovarian cancer, p=0.037, and maternal family history of any cancer, p=0.020)
      conferred a significantly increased risk of carrying a BRCA1 mutation compared
      with ovarian cancer patients without such a history. However, the majority of
      ovarian cancer patients with these family histories and other suggestive
      histories tested negative for mutations. CONCLUSIONS: Approximately 10% of
      ovarian cancers occur in association with genetic mutations known to predispose
      to the disease. A routinely obtained family history is an unreliable way to
      identify patients who might harbor mutations. The majority of ovarian cancer
      patients with suggestive family histories test negative for known gene mutations,
      perhaps suggesting the existence of additional undiscovered genes predisposing to
      ovarian cancer.

PMID- 9579429
TI  - How accurate is fetal biometry in the assessment of fetal age?
AB  - OBJECTIVE: The purpose of the study was to assess the accuracy of fetal biometry
      in the midtrimester of pregnancy in the assignment of fetal age. STUDY DESIGN: A
      total of 152 singleton, 67 twin, and 19 triplet gestations resulting from in
      vitro fertilization with ultrasonographic fetal biometry from 14 to 22 weeks made
      up the study population. A gestational age prediction equation was derived from
      singletons with the use of stepwise linear regression. This equation was compared
      with 38 previously published equations and then applied to the twin and triplet
      populations. RESULTS: Head circumference was the best predictor of gestational
      age (random error [SD] 3.77 days). Addition of abdominal circumference and femur
      length to head circumference improved the accuracy of the dating equation (random
      error 3.35 days). Most dating formulas had systematic errors of <1 week. The
      systematic error was -0.32 day for averaging the singleton-based predictions for
      twins and -1.26 days for triplets. CONCLUSIONS: Gestational age assessment with
      the use of fetal biometry from 14 to 22 weeks is accurate for singleton, twin,
      and triplet gestations.

PMID- 9579430
TI  - The timing of congenital brachial plexus injury: a study of electromyography
      findings in the newborn piglet.
AB  - OBJECTIVE: Permanent congenital brachial plexus palsy is a recognized serious
      complication associated with shoulder dystocia. The timing and etiology of this
      injury remains controversial. Previous authorities have used adult-derived, non
      brachial plexus data to extrapolate the anticipated timing for electromyographic
      denervation changes to date such injuries in the newborn. With use of a domestic
      swine model, this investigation tests the hypothesis that electromyographic
      evidence of brachial plexus denervation in the newborn is temporally different
      than that in the adult. STUDY DESIGN: Five healthy 2-day-old and two adult pigs
      underwent unilateral sharp transection of the brachial plexus. Daily
      electromyographic studies were performed in brachial plexus innervated muscle
      groups on the involved and contralateral (control) front limbs. Postmortem
      measurements of the transected nerve segments were obtained in one piglet and one
      adult animal. Representative hard copy recordings of individual electromyographic
      studies were collected. RESULTS: Immediately after surgical transection of the
      brachial plexus, no electromyographic evidence of denervation was observed.
      Uniformly in the newborn piglets, at 24 hours after transection, denervation in
      the form of fibrillation potentials, positive sharp waves, and complex repetitive
      discharges was seen. Serial testing demonstrated proximal to distal gradients of
      denervation over the next 24 to 48 hours. A delay in electromyographic evidence
      of denervation was observed in the two adult pigs until days 5 and 8,
      respectively. Control limb studies remained normal throughout the study period.
      Nerve length measurements for individual muscle groups were as follows for the
      adult and newborn pigs, respectively: deltoid 11.4 cm, 2.5 cm; cleidobrachialis
      16.0 cm, 4.0 cm; triceps 15.5 cm, 4.5 cm; forelimb flexors 26.0 cm, 6.5 cm; and
      extensor carpi radialis 31.0 cm, 9.0 cm. CONCLUSION: Electromyographic evidence
      of brachial plexus denervation after surgical transection differs between the
      newborn and the adult pig. Consistent with wallerian degeneration, a correlation
      exists between length of the distal nerve segment and timing for
      electromyographic signs of denervation. These findings suggest it would be
      inappropriate to extrapolate the anticipated timing for electromyographic changes
      in the newborn on the basis of previously established adult non-brachial plexus
      data.

PMID- 9579431
TI  - Fetal assessment based on fetal biophysical profile scoring. VIII. The incidence
      of cerebral palsy in tested and untested perinates.
AB  - OBJECTIVE: The intent of this comparative clinical study was fourfold: (1) to
      determine the incidence of cerebral palsy in a large obstetric population, (2) to
      compare the incidence of cerebral palsy in patients at high risk referred for and
      managed according to the fetal biophysical profile score result with the
      incidence among unreferred and untested patients, (3) to determine the
      relationship, if any, between the last fetal biophysical profile score and the
      incidence of cerebral palsy, and (4) to categorize cases of cerebral palsy
      according to the clinical parameters and the probable time and nature of the
      damaging insult. STUDY DESIGN: In this retrospective 5-year comparative study
      (1987 to 1991) the incidence of cerebral palsy was determined by analysis of
      International Classification of Diseases, Ninth Revision, -coded related medical
      services. The clinical records were then sought and reviewed in index cases and
      obstetric, neonatal, and postnatal clinical data were abstracted. Cross
      correlation with partial registries was done to confirm completeness of capture
      of index cases. The population of referred high-risk patients who received serial
      fetal biophysical profile scoring and were managed according to test results was
      determined by review of a prospective computer-stored database and by review of
      patient log books. The population of untested patients was calculated as the
      residual of total cases minus tested cases. The rate of cerebral palsy for all
      patients and for the tested and untested population was calculated and compared.
      The tested and untested perinates were compared for birth age, weight, and
      assigned timing or etiology of cerebral palsy. In the tested population the
      distribution of test results by last recorded biophysical profile score was
      determined and the relationship between the last test result and cerebral palsy
      and predictive accuracy parameters of the fetal biophysical profile score were
      calculated. RESULTS: The incidence of cerebral palsy among the 84,947 live births
      was 3.68 per 1000 live births (313 cases). The rate of cerebral palsy in the
      26,290 referred high-risk tested patients was 1.33 per 1000 (35 cases) compared
      with a rate of 4.74 per 1000 live births in the 58,657 untested mixed low
      risk/high-risk patients (278 cases). These differences were highly significant. A
      significant declining trend in the annual incidence of cerebral palsy was
      observed in the total population and the untested population, whereas the rate in
      the tested population remained relatively constant over the 5-year study
      interval. The differences in the cerebral palsy rate between the tested and
      untested population were not related to differences in gestational age, birth
      weight, or assigned timing or etiology category. In the tested population the
      relationship between the incidence of cerebral palsy and the last test fetal
      biophysical profile score was inverse, exponential, and highly significant.
      CONCLUSIONS: Antepartum assessment by fetal biophysical profile scoring is
      associated with a significant reduction in the incidence of cerebral palsy
      compared with untested patients. The relationship between the last test score and
      the incidence of cerebral palsy is inverse and exponential, suggesting that
      antenatal asphyxia is an important and potentially avoidable cause of cerebral
      palsy.

PMID- 9579432
TI  - Does magnesium sulfate given for prevention of eclampsia affect the outcome of
      labor?
AB  - OBJECTIVE: The purpose of this study was to determine whether magnesium sulfate
      given for prevention of eclampsia affected labor outcomes compared with
      phenytoin, which is not known to impede uterine activity when given in
      anticonvulsant doses. STUDY DESIGN: Secondary analysis was performed of a study
      of women with pregnancy-induced hypertension who were admitted for delivery and
      randomly assigned to receive either magnesium sulfate or phenytoin for eclampsia
      prophylaxis. Nulliparous women with a singleton pregnancy in cephalic
      presentation at term were selected for analysis in an effort to limit the
      influence of confounding variables such as preterm birth and malpresentations on
      labor management and outcomes. Similarly, women who had severe preeclampsia and
      who received labor epidural analgesia were excluded. RESULTS: A total of 2138
      women were randomized to receive magnesium sulfate or phenytoin in the primary
      study. A total of 905 nulliparous women met the inclusion criteria for this
      secondary analysis; 480 had been randomized to phenytoin and 425 were given
      magnesium sulfate. The two groups were similar demographically. Labor outcomes
      such as (1) oxytocin stimulation, (2) admission-to-delivery intervals, (3)
      prolonged second-stage labor, (4) forceps delivery, and (5) cesarean delivery
      were not affected by maternal treatment with magnesium sulfate. CONCLUSION:
      Compared with phenytoin, magnesium sulfate given for intrapartum treatment of
      pregnancy-induced hypertension does not significantly affect labor outcomes.

PMID- 9579433
TI  - Proliferation and apoptosis of fibroblasts and smooth muscle cells in rat uterine
      cervix throughout gestation and the effect of the antiprogesterone onapristone.
AB  - OBJECTIVE: The purpose of this study was to determine the relative percentages of
      apoptosis and proliferation in fibroblasts and cervical smooth muscles throughout
      gestation and the effect of an antiprogesterone on these processes. STUDY DESIGN:
      Rats were studied at days 5, 15, 18, and 21 and immediately postpartum (day 22).
      Apoptosis and proliferation as detected by specific immunohistochemistry
      quantitative morphometric analysis was performed. Onapristone, an
      antiprogesterone, was used to study effects of hormonal change on these processes
      in 16- and 19-day timed-pregnant rats. RESULTS: Proliferation of fibroblasts and
      smooth muscle cells was highest in early pregnancy and decreased progressively,
      whereas apoptosis increased progressively in later pregnancy. Onapristone
      inhibited apoptosis. CONCLUSION: Changes in cervical cellular turnover are
      initiated early in gestation and are under hormonal influence. Antiprogesterone
      inhibits cell death at days 16 and 19 of gestation.

PMID- 9579434
TI  - Fetal and neonatal mortality in the postterm pregnancy: the impact of gestational
      age and fetal growth restriction.
AB  - OBJECTIVE: Our purpose was to examine the impact of gestational age and fetal
      growth restriction on fetal and neonatal mortality rates in the postterm
      pregnancy. STUDY DESIGN: All deliveries occurring in Sweden between Jan. 1, 1987,
      and Dec. 31, 1992, were evaluated for participation in this study. Data were
      derived from the National Swedish Medical Birth Registry. Pregnancies were
      selected for inclusion in the study on the basis of the following criteria: (1)
      singleton pregnancy, (2) reliable dates, (3) gestational age > or = 40 weeks, and
      (4) maternal age 15 to 44 years. Fetal growth restriction was defined as birth
      weight <2 SD below the mean for gestational age. A total of 181,524 pregnancies
      met the inclusion criteria and formed the study population. Fetal and neonatal
      mortalities at 40 weeks' gestation were used as reference levels. Logistic
      regression analysis was used to estimate the independent effects of gestational
      age and fetal growth restriction on fetal and neonatal mortality rates. RESULTS:
      A significant rise in the odds ratio for fetal death was detected from 41 weeks'
      gestation and on (odds ratios 1.5, 1.8, and 2.9 at 41, 42, and 43 weeks,
      respectively). Odds ratios for neonatal mortality did not demonstrate a
      significant gestational age dependency. Fetal growth restriction was associated
      with significantly higher odds ratios for both fetal and neonatal mortality rates
      at every gestational age examined (with odds ratios ranging from 7.1 to 10.0 for
      fetal death and from 3.4 to 9.4 for neonatal death). CONCLUSIONS: Postterm
      pregnancies have long been considered to be at high risk for adverse perinatal
      outcome. This study documents a small but significant increase in fetal mortality
      in accurately dated pregnancies that extend beyond 41 weeks of gestation. This
      study also demonstrates that fetal growth restriction is independently associated
      with increased perinatal mortality in these pregnancies.

PMID- 9579435
TI  - Effects of aging and gonadal failure on the hypothalamic-pituitary axis in women.
AB  - OBJECTIVE: Our aim was to determine the effect of aging on the hypothalamic
      pituitary-gonadal axis function. STUDY DESIGN: We studied 9 women aged 25 to 40
      years with well-defined idiopathic premature ovarian failure and compared them
      with 8 women aged 51 to 70 years who had age-appropriate menopause. All women
      underwent 24 hours of frequent blood sampling every 10 minutes before and after
      replacement with transdermal estradiol targeted to achieve serum concentrations
      of approximately 100 pg/ml. RESULTS: In the absence of estrogen exposure, women
      with premature ovarian failure demonstrated a greater 24-hour mean luteinizing
      hormone concentration compared with that in the older women with age-appropriate
      menopause (32.3+/-4.3 mlU/ml vs 19.2+/-2.4 mlU/ml, p=0.0001). Despite the lesser
      luteinizing hormone serum levels in the older group, the luteinizing hormone
      pulse frequency per 24 hours was similar (22.1+/-3.0 pulses per 24 hours in
      prematurely menopausal women vs 21.9+/-2.5 pulses per 24 hours in the older
      postmenopausal women, p=0.94). When exposed to estrogen, mean luteinizing hormone
      concentrations decreased to 11.6+/-2.7 mlU/ml in prematurely menopausal women
      versus 4.4+/-1.0 mlU/ml in older postmenopausal women, p=0.017. Both groups had
      suppressed mean luteinizing hormone secretion compared with their paired, non
      estradiol-exposed studies, p=0.0001. Frequency of luteinizing hormone pulsations
      was reduced to 16.5+/-3.5 pulses per 24 hours in prematurely menopausal women
      exposed to estradiol (p < 0.0058, compared with non-estradiol-exposed women).
      Further reduction was observed in older postmenopausal women (11.5+/-1.1 pulses
      per 24 hours, p=0.0001, compared with nonestradiol exposure, and p=0.0125, vs
      prematurely menopausal, estradiol-exposed women). Pulse amplitude was suppressed
      in both prematurely menopausal women (5.6+/-0.5 mlU/ml to 2.3+/-0.5 mlU/ml,
      p=0.0001) and older postmenopausal women (3.6+/-0.4 mlU/ml to 2.3+/-0.6 mlU/ml
      p=0.04) in the presence of estradiol. Although luteinizing hormone pulse
      amplitudes were greater in the women with premature menopause in the absence of
      estradiol (p=0.0028) compared with those in older postmenopausal women, pulse
      amplitudes became similar in the presence of estradiol. Parallel changes in mean
      follicle-stimulating hormone were observed. Women with premature ovarian failure
      had a mean follicle-stimulating hormone level of 71.1+/-9.4 mlU/ml that was
      suppressed to 18.0+/-4.1 mlU/ml after estradiol exposure (p=0.0001); values in
      older postmenopausal women were 45.9+/-6.0 and 10.3+/-2.0, respectively
      (p=0.0001). Although the women with premature ovarian failure secreted more
      follicle-stimulating hormone in the absence and presence of estradiol, only the
      former situation was statistically significant (p=0.0008 and p=0.23,
      respectively). CONCLUSIONS: These data suggest that there is an age-related
      decrease in gonadotropin secretion that may be hypothalamic or pituitary in
      origin. There is less luteinizing hormone secreted in women older than age 50.
      There is greater suppression of luteinizing hormone and follicle-stimulating
      hormone secretion by estradiol in aged women. Thus these data indicate that
      postmenopausal hormone changes involve central hypothalamic-pituitary
      alterations, as well as ovarian changes.

PMID- 9579437
TI  - What is a good physician in this new era?

PMID- 9579436
TI  - Fetal anomaly detection by second-trimester ultrasonography in a tertiary center.
AB  - OBJECTIVE: Our purpose was to determine the relative accuracy of indicated versus
      screening second-trimester ultrasonography for detection of fetal anomalies and
      to assess the cost effectiveness of anomaly screening. STUDY DESIGN: The study
      population consisted of 2031 pregnant women with singleton gestations who
      prospectively underwent ultrasonographic scanning between 15 and 22 weeks and
      received complete obstetric care at the Medical University of South Carolina
      between July 1, 1993, and June 30, 1996. Patients were divided into two groups:
      (1) indicated and (2) screening. The cost of screening ultrasonography was
      compared with the cost of newborn care for selected anomalous fetuses. RESULTS:
      Forty-seven fetuses (2.3%) were diagnosed by ultrasonography as having a major
      anomaly: 8.6% in the indicated group and 0.68% in the screening group (p=0.001).
      The sensitivity for detecting the anomalous fetus was 75.0% overall: 89.7% in the
      indicated group and 47.6% in the screening group (p=0.001). Of the 47 patients
      diagnosed with fetal anomalies, 11 (23.4%) chose pregnancy termination; of the 35
      (74.5%) live-born anomalous infants, 29 (82.9%) were discharged alive. Projected
      newborn cost savings offset the cost of routine midtrimester screening.
      CONCLUSIONS: Detection of anomalous fetuses was significantly better in the
      indicated compared with the screening group. Nevertheless, routine
      ultrasonographic screening appeared cost-effective in our population.

PMID- 9579438
TI  - What is a good doctor? Patient perspective.

PMID- 9579439
TI  - Medicine: business or profession, art or science?

PMID- 9579440
TI  - Inhibition of amniotic prostaglandin E release by ampicillin.
AB  - OBJECTIVE: The effect of antibiotics in the prevention of preterm labor needs to
      be further investigated. The aim of this study was to determine the effect of
      ampicillin on prostaglandin E release from amnion as a possible explanation for
      its ability to retard preterm labor. STUDY DESIGN: The effect of the beta-lactam
      antibiotic ampicillin on prostaglandin E release from human amnion was tested
      under basal and stimulated conditions. RESULTS: Ampicillin dose dependently
      inhibits basal prostaglandin E release from amnion in both static and dynamic
      conditions. In our experiments, 10(-7) mol/L ampicillin (a concentration able to
      significantly inhibit prostaglandin E output) leaves the microbiologic features
      of the medium substantially unmodified up to 5 hours of incubation. Moreover, the
      drug reversibly counteracts the prostaglandin E elevation induced by arachidonic
      acid or oxytocin. CONCLUSION: This finding (i.e., that ampicillin inhibits
      prostaglandin E release from amnion) may offer an explanation for a beneficial
      response to ampicillin therapy in the case of preterm labor even in the absence
      of bacterial infection.

PMID- 9579441
TI  - Biochemical analyses of mesenchymal fluid in early pregnancy.
AB  - OBJECTIVE: Our purpose was to compare the biochemical composition of the fluid
      contained in pathologic and physiologic cavities in early pregnancy. STUDY
      DESIGN: The level of urea, creatinine, electrolytes, enzymes, total protein, and
      alpha-fetoprotein and the affinity of alpha-fetoprotein for concanavalin A
      Sepharose was measured in samples of vesicular fluid from complete (n=2) and
      partial (n=1) mole, nuchal fluid (n=4), and cystic hygroma fluid (n=4). For
      comparison samples of maternal serum (n=32), amniotic fluid (n=32), coelomic
      fluid (n=15), and fetal blood (n=13) were obtained from normal pregnancies at 10
      to 16 weeks' gestation. RESULTS: Urea concentration was lower, whereas sodium,
      potassium, and total protein concentrations were higher in vesicular fluid than
      in amniotic and coelomic fluid. Urea, creatinine, sodium, potassium, chloride,
      and beta2-microglobulin concentrations did not vary between nuchal or cystic
      hygroma fluid and amniotic fluid or fetal serum. The concentration of total
      protein in nuchal and hygroma fluid was significantly lower than in fetal serum
      and significantly higher than in amniotic fluid. The amniotic fluid contained
      extremely high tau-glutamyltransferase concentration compared with the other
      fluids and fetal serum. Alkaline phosphatase and amylase were not detectable in
      coelomic fluid, fetal serum, or nuchal and hygroma fluid. The nuchal and hygroma
      fluid composition was similar except for total protein and alpha-fetoprotein
      concentrations, which were significantly higher in nuchal than in hygroma fluid.
      The vesicular fluid from the partial mole, fetal serum, and nuchal and hygroma
      fluid contained extremely high alpha-fetoprotein concentrations, which were
      significantly higher that those found in amniotic fluid. In complete mole alpha
      fetoprotein molecules were of the yolk sac type, whereas they were of the liver
      type in nuchal and hygroma fluid. CONCLUSIONS: The composition of vesicular fluid
      in complete mole reflects a possible origin from the maternal plasma, yolk sac,
      and trophoblast, whereas the composition of nuchal and cystic hygroma fluid
      suggests a leakage from the fetal circulation.

PMID- 9579442
TI  - Effect of betamethasone in vivo on placental corticotropin-releasing hormone in
      human pregnancy.
AB  - OBJECTIVE: The objective was to determine the effects of in vivo administration
      of prenatal betamethasone in patients at 26 to 35 weeks' gestation on
      corticotropin-releasing hormone concentrations in maternal and fetal plasma and
      amniotic fluid, and on corticotropin-releasing hormone localization in placenta
      and fetal membranes. STUDY DESIGN: A total of 49 pregnant women at risk for
      preterm delivery between 26 and 35 weeks' gestation were studied. Twenty-six
      patients received betamethasone (12 mg intramuscularly) for stimulation of fetal
      lung maturity. Cord blood, amniotic fluid, placental tissue, and fetal membranes
      were obtained from 22 of these patients at delivery by elective cesarean section
      at 33.8+/-2.4 weeks' gestation. In control patients (n=23) at comparable
      gestational age, blood samples were taken for hormone analysis (n=8), and cord
      blood, amniotic fluid, and tissues were collected at elective cesarean section at
      34.1+/-2.3 weeks' gestation. Concentrations of corticotropin-releasing hormone,
      adrenocorticotropic hormone, and cortisol were determined by radioimmunoassay.
      Localization of tissue immunoreactive corticotropin-releasing hormone was
      assessed by immunohistochemistry. RESULTS: Betamethasone caused approximately 90%
      reduction in maternal cortisol and 50% reduction in maternal plasma
      adrenocorticotropic hormone. In patients at >30 weeks' gestation, there was a
      significant increase in maternal plasma corticotropin-releasing hormone
      concentrations after betamethasone; maternal corticotropin-releasing hormone was
      not altered significantly in untreated patients. Corticotropin-releasing hormone
      levels were raised in umbilical cord blood by 48 hours and in amniotic fluid 1
      week after betamethasone administration. There was increased immunohistochemical
      staining for corticotropin-releasing hormone in placental syncytiotrophoblast and
      in fetal membranes of patients treated with betamethasone. CONCLUSIONS: These
      studies provide the first evidence for in vivo stimulation of plasma
      corticotropin-releasing hormone, likely of placental origin, by glucocorticoids
      in third trimester human pregnancy. The results suggest that increases in
      endogenous cortisol during normal gestation may contribute to placental
      corticotropin-releasing hormone output and to the rise in maternal plasma
      corticotropin-releasing hormone concentrations during late pregnancy.

PMID- 9579444
TI  - Are the cytokines interleukin-6 and angiogenin stable in frozen amniotic fluid?
AB  - OBJECTIVE: To determine the stability of cytokines in frozen stored amniotic
      fluid samples, we measured angiogenin, a potent inducer of neovascularization and
      interleukin-6, an inflammatory cytokine, in the same sample of midtrimester
      amniotic fluid 1 year apart. STUDY DESIGN: In this study paired aliquots of
      amniotic fluid kept at -70 degrees C were immunoassayed for angiogenin and
      interleukin-6 at two different time periods 1 year apart. Inclusion criteria were
      (1) samples with clearly identifiable numbers, (2) no evidence of breaks in
      sealing of samples, and (3) singleton gestation. Amniotic fluid was immunoassayed
      for angiogenin and interleukin-6 in July 1995 and 1996. Angiogenin sensitivities
      were 0.078 and 0.026 ng/ml, interassay coefficients of variation were 3.8% and
      4.6%, and intraassay coefficients of variation were 2.7% and 2.9%, respectively,
      in 1995 and 1996. Interleukin-6 sensitivities were 1.74 and 2.37 pg/ml,
      interassay coefficients of variation were 8.9% and 2.6%, and intraassay
      coefficients of variation were 3.5% and 1.9%, respectively, in 1995 and 1996.
      Statistical analysis included paired t test, Wilcoxon signed-rank test, and
      regression with p < 0.05 significant. Angiogenin and interleukin-6 values were
      normalized with natural log transformation for statistical analysis. RESULTS:
      Paired amniotic fluid samples from 30 patients were immunoassayed from 1993 to
      1995. The values of angiogenin were significantly lower in the 1996 assay
      compared with the 1995 assay (median 12.4 [range 5.6 to 61.3] vs 26.7 [range 13.6
      to 159.2] ng/ml, p < 0.001). A significant correlation was found between the
      change in angiogenin levels and the year of the sample, with older samples having
      the greatest change in values (r=0.5, p=0.008). The values of interleukin-6 were
      significantly lower in the 1996 assay compared with the 1995 assay (median 230.8
      [range 40.9 to 3711.3] vs 289.2 [range 53.7 to 19100.0] pg/ml, p < 0.001).
      CONCLUSIONS: Angiogenin and interleukin-6 values in amniotic fluid appear to
      decrease with time despite optimal freezing conditions. The year of sampling and
      length of storage should be taken into consideration when evaluating amniotic
      fluid cytokine levels from stored samples.

PMID- 9579443
TI  - A new screening protocol combining urine beta-core fragment and ultrasonography
      for Down syndrome detection.
AB  - OBJECTIVE: Our purpose was to ascertain the screening efficiency of a new
      midtrimester Down syndrome detection protocol that combines maternal urine
      testing and ultrasonographic examination. STUDY DESIGN: In a prospective study,
      beta-core fragment, the stable end product of human chorionic gonadotropin
      metabolism, was measured in maternal urine. The results were standardized for
      urine creatinine levels. The study was performed in women undergoing midtrimester
      genetic amniocentesis (15 to 24 weeks' gestation). Urine beta-core fragment
      values were expressed as multiples of the normal median for gestational age. The
      screening performance of a combination of ultrasonographic parameters and urine
      beta-core values for Down syndrome detection was determined. RESULTS: A total of
      511 singleton pregnancies in women undergoing amniocentesis were studied, 18 of
      the women (3.5%) had a Down syndrome fetus. A urine beta-core fragment level > or
      = 97th percentile had a sensitivity of 61.1% and a false-positive rate of 3.2%.
      An abnormal prenatal screen was defined as a urine beta-core level > or = 97th
      percentile, increased nuchal thickness (> or = 5 mm), or the presence of gross
      structural defects. Corresponding values for the screening efficiency of an
      abnormal prenatal screen were sensitivity of 77.8% and a false-positive rate of
      4.1%. With an abnormal prenatal screen the odds ratio is 82.8 (95% confidence
      interval 22.6 to 364.9) for having a Down syndrome fetus. CONCLUSION: The
      presence of an abnormal maternal urine beta-core level, a gross ultrasonographic
      anomaly, or increased nuchal thickness had a high detection rate and a low false
      positive rate for Down syndrome. This novel screening algorithm is useful for
      further delineating the risk status in patients at high risk who are reluctant to
      undergo or decline genetic amniocentesis.

PMID- 9579445
TI  - Effects of adding C-19 versus C-21 progestin to conjugated estrogen in moderately
      hypercholesterolemic postmenopausal women.
AB  - OBJECTIVE: Our purpose was to compare the effects on fasting plasma lipoprotein
      lipids of adding low dosage C-19 continuous progestin (dl-norgestrel) versus
      conventional low-dosage continuous C-21 progestin (medroxyprogesterone acetate)
      to cyclic conjugated estrogen therapy. STUDY DESIGN: Nine hypercholesterolemic
      postmenopausal women with intact uteri were randomly assigned in a prospective,
      double-blind, two-period crossover study of conjugated estrogen plus either (1)
      dl-norgestrel (0.05 mg/day) or (2) medroxyprogesterone acetate (2.5 mg/day) for 1
      year and after an appropriate washout period were switched to the alternative
      regimen for another year. Four subjects received conjugated estrogen only.
      RESULTS: Compared with baselines, each of the C-19 and C-21 progestin regimens
      significantly increased plasma high-density lipoprotein cholesterol (15% vs 12%)
      and reduced the ratio of total cholesterol/high-density lipoprotein cholesterol
      (20% vs 15%, respectively), but only the former significantly reduced plasma
      triglycerides (24% vs 0.3%, p < 0.05). CONCLUSIONS: Low dosages of either dl
      norgestrel (C-19) or medroxyprogesterone acetate (C-21) when combined with
      conjugated estrogen significantly improve plasma lipoprotein lipids of
      postmenopausal women.

PMID- 9579446
TI  - Laparoscopic surgery: the effects of insufflation gas on tumor-induced lethality
      in nude mice.
AB  - OBJECTIVE: The aim of the study was to examine the effect of helium (group 2),
      carbon dioxide (group 3), and heated carbon dioxide (group 4) pneumoperitoneum on
      survival in case of intraabdominal spread of tumor cells in nude mice. STUDY
      DESIGN: The pneumoperitoneum was induced by a microhysteroflator with an
      intraperitoneal pressure of 8 mm Hg for 30 minutes. A washed tumor solution (0.4
      ml) of a mesothelioma was injected intraperitoneally. RESULTS: The survival rate
      of group 3 was significantly reduced compared with the controls (group 1) and
      group 4. The latter groups showed similar survival rates. In groups 2 and 3 no
      significant differences in survival rate were observed. CONCLUSION: Clinical
      observations and the results of this animal study warn against the use of
      standard unheated carbon dioxide pneumoperitoneum in case of malignant tumors.
      Heated carbon dioxide seems to be advantageous.

PMID- 9579447
TI  - To peritonealize or not to peritonealize? A randomized trial at abdominal
      hysterectomy.
AB  - OBJECTIVES: Our purpose was to determine whether nonclosure of the visceral and
      parietal peritoneum alters the intraoperative or postoperative course at
      abdominal hysterectomy. STUDY DESIGN: The setting was a gynecology unit in a
      university teaching hospital. A parallel-group, single-blind randomized
      controlled trial was performed on 144 women who underwent abdominal hysterectomy
      with or without salpingo-oophorectomy. Seventy-six women were allocated to the
      control "closed" group and 68 women to the study "open" group. The main outcome
      measures were operative time, estimated blood loss, postoperative pain assessed
      by visual analog scale, and amount of postoperative analgesia. RESULTS: The mean
      operative time was shorter by 10 minutes (p < 0.001) and there was a 45 ml
      reduction of estimated blood loss in the nonclosure group (p=0.03). There were no
      differences in postoperative pain in the two groups. CONCLUSIONS: Peritoneal
      closure at abdominal hysterectomy provides no immediate postoperative benefits
      while unnecessarily lengthening surgical time and anesthesia exposure. We suggest
      that the traditional practice of visceral and parietal peritoneal closure be
      abolished at abdominal hysterectomy.

PMID- 9579448
TI  - The effect of tamoxifen and transdermal 17beta-estradiol on cerebral arterial
      vessels: a randomized controlled study.
AB  - OBJECTIVES: Our objective was to study the effects of tamoxifen on cerebral
      arterial reactivity. STUDY DESIGN: We studied the reactivity of both the internal
      carotid artery and the middle cerebral artery during a 12-month period of
      administration of either oral tamoxifen or transdermal estradiol or no treatment.
      A total of 45 healthy postmenopausal women who had undergone hysterectomy were
      followed up. Patients were randomly allocated to treatment with either oral
      tamoxifen 20 mg/day or transdermal estradiol 50 microg/day or nothing (15
      patients in each group). They all underwent Doppler examinations of the internal
      carotid artery and middle cerebral artery at the beginning of the study and after
      2, 6, and 12 months of treatment. The pulsatility index was measured. RESULTS: In
      the women given transdermal estradiol the pulsatility index of both the internal
      carotid artery and the middle cerebral artery was significantly reduced compared
      with that in the controls. Tamoxifen did not induce variations of pulsatility
      index in either artery during all the study period. The difference between the
      effect of the two drugs on the pulsatility index of both arteries was highly
      significant. CONCLUSIONS: Our findings demonstrate that tamoxifen does not cause
      any variation in the pulsatility index of cerebral arteries. The action of
      transdermal estradiol on the pulsatility index of cerebral arteries in
      postmenopausal women is the expression of a generalized action of estrogens on
      arterial vessels, and if this expression plays a role in the protective effect of
      hormone replacement therapy on risk of cardiovascular disease, tamoxifen
      treatment in healthy postmenopausal women should be considered with renewed
      caution.

PMID- 9579449
TI  - Value of laparoscopic evaluation of paraaortic and pelvic lymph nodes for
      treatment of cervical cancer.
AB  - OBJECTIVE: Laparoscopy was used to identify and localize suspicious lymph nodes
      in patients with cervical cancer. STUDY DESIGN: Eighty-four patients with
      cervical cancer International Federation of Gynecology and Obstetrics stage IA2
      to IV were staged by laparoscopic paraaortic and pelvic lymphadenectomy. The
      accuracy of laparoscopic assessment of lymph node status was compared with the
      histologic result. Positive lymph nodes were localized topographically by use of
      laparoscopy. RESULTS: Sensitivity and specificity of laparoscopic evaluation for
      identifying positive paraaortic and pelvic lymph nodes was 92.3%. Combination of
      laparoscopic evaluation and frozen section helped to diagnose all patients with
      involved lymph nodes correctly. In 13 of 84 (15.4%) patients the result of lymph
      node assessment by laparoscopic evaluation and frozen section changed primary
      therapy. In two of these patients one positive lymph node was located in the
      lateral part of the cardinal ligament, and the hysterectomy was extended to be a
      more radical procedure. CONCLUSIONS: Laparoscopic evaluation identified the lymph
      node status in patients with cervical cancer with high accuracy. Topographic
      localization showed that the lateral part of the cardinal ligament is involved
      early in lymph node spread.

PMID- 9579450
TI  - Uterine activity during pregnancy and labor assessed by simultaneous recordings
      from the myometrium and abdominal surface in the rat.
AB  - OBJECTIVES: The aim of this study was to analyze records of uterine electrical
      activity made from the abdominal surface of pregnant and laboring rats to examine
      whether similar quantitative information can be extracted as from direct
      recording from the uterine muscle. STUDY DESIGN: Electrical activity during
      pregnancy (nonlabor, days 18 to 22), term labor (day 22), and preterm labor
      (onapristone injected on day 18, delivery on day 19) was measured with use of
      electrodes attached to the uterine wall and to the abdominal surface. The fast
      Fourier transform and wavelet transforms were obtained for representative
      electromyographic bursts. Power spectra were generated. Intrauterine pressure was
      also measured. RESULTS: (1) Several parameters have been identified for use in
      following up the progressive increase in uterine activity that occurs in
      preparation for and during labor. Analyses of amplitude, frequency, and percent
      time active represent a convenient method for objectively determining the
      efficiency of uterine contraction. (2) Most of the changes in these parameters
      appear in the last 24 hours before delivery. (3) Although the uterine
      electromyographic signals on the abdominal surface are attenuated, the abdominal
      surface signals are generally similar to the signals obtained from the uterine
      muscle during pregnancy and during preterm and term labor. (4) The
      characteristics of onapristone-induced preterm labor are generally similar to
      those of spontaneous term labor. CONCLUSIONS: Recording of uterine
      electromyographic activity from the abdominal surface may be useful in following
      the progression of pregnancy and in predicting and diagnosing labor.

PMID- 9579451
TI  - Role of nitric oxide on the central hemodynamic response to acute volume
      expansion in the pregnant rat.
AB  - OBJECTIVES: Our hypothesis was that during pregnancy nitric oxide acts as
      mediator in the hemodynamic response to volume expansion. STUDY DESIGN: The study
      was performed on 12 rats on days 19 to 20 of pregnancy. Six rats were injected
      intravenously with hexamethonium bromide plus the inhibitor of nitric oxide
      synthase L-nitro-arginine methyl ester. For a control group, six rats were
      injected with hexamethonium bromide plus the L-nitro-arginine methyl ester
      vehicle. A volume expansion (1.2% body weight) was performed in both groups by
      intravenous infusion of bovine albumin (6%) solution. RESULTS: In the control
      group volume expansion induced a hyperdynamic circulation characterized by
      increased cardiac output, decreased total vascular resistance, and no change in
      arterial pressure; however, in the study group volume expansion induced a pressor
      response without hyperdynamic circulation. CONCLUSION: During pregnancy volume
      expansion induces a hyperdynamic circulatory state possibly mediated by nitric
      oxide release. A defect in the release of nitric oxide may be responsible for an
      inadequate hemodynamic response to volume expansion.

PMID- 9579452
TI  - Toward universal criteria for gestational diabetes: relationships between seventy
      five and one hundred gram glucose loads and between capillary and venous glucose
      concentrations.
AB  - OBJECTIVES: Replacement of the two-step, 100 gm, 3-hour National Diabetes Data
      Group procedure by the one-step, 75 gm, 2-hour World Health Organization oral
      glucose tolerance test has been hindered by a paucity of data comparing the two
      tests during pregnancy. The current series compared 100 gm and 75 gm glucose
      loads and glucose measurements in venous plasma or capillary blood. STUDY DESIGN:
      After a 75 gm oral glucose tolerance test 30 gestational diabetics and 30
      metabolically healthy pregnant women were randomly assigned to a second 75 or 100
      gm test within 3+/-1.3 (mean+/-SD) days. Glucose levels at both tests was
      measured in capillary blood and venous plasma, as were insulin and C peptide.
      RESULTS: In controls 1-hour maternal glucose levels (112 vs 128 mg/dl) and 2-hour
      levels (104 vs 113 mg/dl) differed significantly after a 75 or 100 gm load
      (paired t test). In gestational diabetes mellitus, however, there was no
      difference (176 vs 178 mg/dl) but a low insulin/glucose quotient at 1 hour. Only
      2-hour levels differed significantly (133 vs 149 mg/dl). In controls glucose
      measurement in capillary blood and venous plasma differed significantly at 1 hour
      (126 vs 115 mg/dl) and 2 hours (111 vs 104 mg/dl) independently of the glucose
      load. In gestational diabetes mellitus, however, glucose measurement in capillary
      blood and venous plasma differed neither in 1-hour levels (179 vs 174 mg/dl) nor
      in 2-hour levels (142 vs 139 mg/dl). CONCLUSION: In metabolically healthy women
      both different loading and different blood fractions lead to statistically
      different blood glucose levels at 1 and 2 hours. In gestational diabetes
      mellitus, however, 1-hour glucose levels do not differ after a 75 or 100 gm load
      or after glucose measurement in capillary blood or venous plasma. This is due to
      elevated insulin resistance shown by a low insulin/glucose quotient at 1 hour.
      For comparison of tests in gestational diabetes mellitus only, 2-hour values must
      be adjusted by 16 mg/dl after different loading.

PMID- 9579453
TI  - Ambulatory blood pressure monitoring in pregnancy: what is normal?
AB  - OBJECTIVE: Noninvasive 24-hour ambulatory blood pressure monitoring holds great
      promise as a useful tool in the management of hypertensive pregnancies and
      pregnancies considered "at risk" for development of preeclampsia. The purpose of
      this study was to define ambulatory blood pressure monitoring parameters
      throughout normal pregnancy, including women considered at risk for development
      of hypertension who continued to have a completely normal pregnancy. STUDY
      DESIGN: Two hundred seventy-six 24-hour ambulatory blood pressure monitoring
      studies were made cross-sectionally with use of a Spacelabs 90207 device
      (validated for use in pregnancy), at one or more of 9 to 17, 18 to 22, 26 to 30,
      and >30 weeks' gestation. Upper limits of normal were defined as the mean plus 2
      SDs for awake and sleep ambulatory blood pressure monitoring results at each
      stage. RESULTS: Average awake upper limits of normal were 130/77, 132/79, 133/81,
      and 135/86 mm Hg at the four stages of pregnancy, respectively. Systolic blood
      pressure fell significantly by 12% to 14% (p < 0.0001) and diastolic blood
      pressure by 18% to 19% (p < 0.0001) during sleep at all stages of pregnancy.
      Awake ambulatory blood pressure monitoring systolic measurements were 11 to 12 mm
      Hg higher than "clinic" measurements (p < 0.001) and diastolic measurements were
      5 to 11 mm Hg higher (p < 0.0001) throughout pregnancy. Maximum blood pressure
      variability ranged from 8 to 13 mm Hg. CONCLUSIONS: The upper limits of normal
      ambulatory blood pressure monitoring-derived measurements rise slightly as
      pregnancy progresses. Awake measurements are higher than "clinic" measurements
      recorded under relaxed conditions by a clinical researcher. The diurnal blood
      pressure fall and variabilities are similar during pregnancy to those seen in
      nonpregnant subjects. These data should provide valuable references for further
      studies of ambulatory blood pressure monitoring in high risk pregnancies.

PMID- 9579454
TI  - Perinatal outcome associated with outpatient management of triplet pregnancy.
AB  - OBJECTIVE: Our goal was to compare the lengths of hospitalization and the
      perinatal outcomes of triplet pregnancies managed with either outpatient or
      inpatient third-trimester bed rest. STUDY DESIGN: Thirty-two triplet pregnancies
      in which outpatient bed rest was prescribed (April 1993 to April 1996) were
      compared with a historic cohort of 34 triplets (January 1985 to March 1993) in
      which routine hospitalization was undertaken in the third trimester. Length of
      hospitalization and maternal and neonatal outcome parameters were compared
      between groups. RESULTS: Maternal inpatient hospital days were significantly
      reduced for the group managed as outpatients, but combined maternal and neonatal
      hospitalization was similar between groups. The mean gestational age at delivery
      was 1 week greater in the hospitalized cohort (33.5+/-2.8 vs 32.5+/-2.8,
      respectively; p=0.16), and average birth weight was correspondingly greater in
      hospitalized cases (1942 gm vs 1718 gm, p < 0.005). Neonatal lengths of stay were
      similar between groups, reflecting earlier postnatal discharge in the outpatient
      era of this study. Preeclampsia occurred with greater frequency in the outpatient
      group (31.3% vs 8.8%, p=0.02), and the neonatal complication of intraventricular
      hemorrhage occurred more commonly in this cohort as well (10/96 vs 1/102,
      p=0.004). All other maternal and neonatal complications were similar between
      groups. CONCLUSION: Reduction in the length of hospitalization attributable to
      outpatient management was limited to the maternal length of stay. It is possible
      that the observed maternal and neonatal complications in the outpatient group may
      have been related to less rigorous bed rest. We would suggest that the
      differences noted in preeclampsia, birth weight, and intraventricular hemorrhage
      support prospective evaluation of bed rest in triplet pregnancy.

PMID- 9579455
TI  - Phosphatidylinositol-specific phospholipase C isoform expression in pregnant and
      nonpregnant rat myometrial tissue.
AB  - OBJECTIVE: Activation of the phosphatidylinositol signaling pathway plays a
      significant role during the intracellular signal transduction events activated
      during agonist-stimulated phasic myometrial contractions. Phospholipase C is an
      essential molecular component of this signaling pathway. These studies sought to
      characterize the expression of phospholipase C isoform messenger ribonucleic acid
      in both pregnant and nonpregnant rat myometrium. STUDY DESIGN: Total cellular
      ribonucleic acid was isolated from myometrial tissue collected from Sprague
      Dawley rats by use of the acidic guanidinium thiocyanate-phenol-chloroform
      extraction technique. After deoxyribonuclease treatment to ensure removal of
      genomic deoxyribonucleic acid, as well as resolution on formaldehyde-1% agarose
      horizontal slab gels to rule out degradation, the ribonucleic acid was used for
      semiquantitative competitive reverse transcriptase-polymerase chain reaction
      studies to evaluate the expression of five of the reported phospholipase C
      isoforms. These studies were performed with isoform-specific 20-mer primers and
      the inclusion of internal standard heterologous deoxyribonucleic acid sequences
      designed with ends homologous to the isoform-specific primers. The identity of
      the polymerase chain reaction products was confirmed with restriction
      endonuclease digestions and homology analysis of the sequenced polymerase chain
      reaction product deoxyribonucleic acid. RESULTS: These reverse transcriptase
      polymerase chain reaction studies have confirmed expression of the phospholipase
      C-beta1a, phospholipase C-beta3, phospholipase C-gamma1, phospholipase C-beta2,
      and phospholipase C-delta1 isoforms in rat myometrial tissue. During pregnancy
      the levels of expression of the phospholipase C-beta3, phospholipase C-gamma1,
      and phospholipase C-delta1 isoforms were increased compared with the levels of
      expression in myometrium from nonpregnant rats. In myometrium from both pregnant
      and nonpregnant animals the phospholipase C-beta1 a isoform was expressed at the
      highest level, the phospholipase C-beta3, phospholipase C-gamma1, and
      phospholipase C-gamma2 isoforms at an intermediate level, and the phospholipase C
      delta1 isoform was expressed at the lowest levels. CONCLUSIONS: These studies
      have confirmed at the messenger ribonucleic acid level significant expression of
      several isoforms of phospholipase C in both pregnant and nonpregnant myometrial
      tissue. These observations provide additional support for the hypothesis that the
      phosphatidylinositol signaling pathway plays an important role in uterine smooth
      muscle.

PMID- 9579456
TI  - Ineffectiveness of oxytocin on intercellular communication between term pregnant
      human myometrial cells before labor.
AB  - OBJECTIVE: The effects of the uterotonic agent oxytocin on intercellular
      communication between term pregnant human myometrial cells before labor were
      studied to investigate its contribution to the synchronicity of uterine
      contractions. STUDY DESIGN: The membrane potential and the input resistance of
      myometrial cells were measured with intracellular micropipettes, and dye-coupling
      assays were concomitantly performed while the tissues were perfused with three
      concentrations of oxytocin (10(-8) mol/L, 10(-7) mol/L, and 10(-6) mol/L). The
      results were compared with those obtained from tissues perfused with gap
      junctional uncoupling agent octanol and those with Tyrode's solution (control).
      RESULTS: Octanol increased input resistance and inhibited dye coupling but did
      not affect membrane potential compared with controls. Oxytocin depolarized
      membrane potential at all studied concentrations. The mean input resistance
      values and detectable dye propagation with oxytocin were similar to controls.
      CONCLUSION: Oxytocin does not contribute to gap junctional intercellular
      communication in term pregnant human myometrium before labor but may affect
      contractions by depolarizing membrane potential.

PMID- 9579457
TI  - Corticotropin-releasing hormone: a biochemical predictor of preterm delivery in a
      pilot randomized trial of the treatment of preterm labor.
AB  - OBJECTIVE: We assessed the ability of maternal plasma corticotropin-releasing
      hormone measurements to predict preterm delivery in the setting of a pilot study
      comparing transdermal glyceryl trinitrate with standard beta-mimetic therapy for
      preterm labor and to determine the effect of these tocolytics on maternal plasma
      corticotropin-releasing hormone concentrations. STUDY DESIGN: Twenty-six
      consecutive patients with preterm labor were randomized to tocolytic treatment
      with transdermal glyceryl trinitrate (n=13) or intravenous albuterol (n=13).
      RESULTS: Plasma corticotropin-releasing hormone immunoreactivity levels were
      higher in women who were delivered within 7 days (41.4+/-13.5 pmol/L) than in
      those continuing to term (14.2+/-2.4 pmol/L, p=0.011) and were not altered by
      treatment. Two women in each of the treatment groups delivered within 7 days of
      the initiation of treatment, two women in the glyceryl trinitrate group were
      changed to albuterol because of persistence of contractions. Glyceryl trinitrate
      treatment was associated with significantly fewer maternal side effects. Neither
      treatment altered umbilical artery Doppler ultrasonographic findings. CONCLUSION:
      Transdermal glyceryl trinitrate is better tolerated than intravenous albuterol
      but may be no more efficacious than albuterol for the treatment of preterm labor.
      Biologic markers such as plasma corticotropin-releasing hormone levels may be an
      important method of identifying women at high risk of preterm delivery.

PMID- 9579458
TI  - Birth injury and macrosomic fetuses: association with mode of delivery.

PMID- 9579459
TI  - Blood pressure measurement in pregnant women in the left lateral recumbent
      position.

PMID- 9579460
TI  - Evaluation of postmenopausal bleeding.

PMID- 9579461
TI  - Diastolic blood pressure and onset of preeclampsia.

PMID- 9579463
TI  - Predictive factors for neonatal morbidity in neonates with an umbilical arterial
      cord pH < 7.00.

PMID- 9579462
TI  - Current Down syndrome risk estimates are reliable.

PMID- 9579464
TI  - Safety of antenatal indomethacin.

PMID- 9579465
TI  - Polymerase chain reaction and restriction fragment length polymorphism mediated
      detection and speciation of Candida spp causing intraocular infection.
AB  - PURPOSE: To determine the usefulness of polymerase chain reaction (PCR) and
      restriction fragment length polymorphism (RFLP) analysis in the identification
      and speciation of Candida spp that causes ocular infection. METHODS:
      Oligonucleotide primers based on the cytochrome P450 L1 A1 demethylase gene were
      used to successfully amplify by PCR a single 1.0-kb and a single 500-bp DNA
      fragment from C. albicans, C. tropicalis, C. krusei, C. glabrata, C.
      parapsilosis, and C. pelliculosa genomic DNA. RFLPs within the PCR product were
      identified after restriction enzyme digestion. RESULTS: The sensitivity of the
      amplification reaction after two rounds of PCR was 10 fg genomic C. albicans DNA
      or one copy of the gene. No amplification product was obtained when DNA from C.
      guilliermondii, Aspergillus fumigatus, Fusarium solani, human leukocytes, or 10
      species of bacteria was used as a template. Experiments with spiked normal
      vitreous demonstrated equal sensitivity as long as the volume of vitreous did not
      exceed 20% of the total PCR volume. RFLP analysis of the PCR product generated
      from each species obtained from the first- and second-round amplification
      products enabled species identification after digestion with specific
      endonucleases. Application of the technique to four clinical samples was
      successful. CONCLUSIONS: It is expected that the simplicity of the DNA extraction
      technique allied with the broad specificity of the outer primers for all
      ophthalmically relevant Candida spp and the sensitivity of the second-round PCR
      will aid in the detection of fungal DNA in small intraocular samples. PCR-RFLP
      analysis has great potential in the rapid detection and identification of Candida
      spp and in the provision of a useful laboratory tool for the future.

PMID- 9579467
TI  - Differential expression of G1 cyclins and cyclin-dependent kinase inhibitors in
      normal and transformed melanocytes.
AB  - PURPOSE: To investigate the levels of the different regulatory proteins involved
      in the G1 progression and G1/S transition in normal and transformed human
      choroidal melanocytes (CM). METHODS: Three choroidal melanoma cell lines and
      three CM cultures were used. The purity of the CM cultures was assessed by
      different approaches, including morphologic study, specific immunostaining, cell
      proliferation behavior, and transforming growth factor-beta1 responsiveness. The
      cell cycle protein levels were evaluated by specific immunoblotting of total
      extracts obtained from the different cell lines. RESULTS: Alterations were
      observed in the expression of cylins D1 and E in the transformed cells, whereas
      the amounts of the cyclin-dependent kinases (CDKs) CDK2 and CDK4 were almost
      identical in both cell types. Although the expression of cyclin H was slightly
      increased in transformed cells, neither the CDK7 level nor the CDK7 and cyclin H
      localizations were altered when compared with those in normal CM. The results
      suggest the absence of the CDK inhibitor (CKI) p21 in two of the three melanoma
      cell lines and, as a main feature, a striking underexpression of p27 in the three
      transformed cell lines. Finally, although the p16 level was almost the same in
      normal and transformed cells, a loss of p16-CDK4 interaction was observed in two
      of the three melanoma cell lines. CONCLUSIONS: Deregulated expression of G1
      cyclins and CKIs and alteration in the interaction of CKIs with CDKs may be
      implicated in the neoplastic transformation of human ocular melanocytes to
      malignant melanoma cells.

PMID- 9579466
TI  - Gene array and expression of mouse retina guanylate cyclase activating proteins 1
      and 2.
AB  - PURPOSE: To identify gene arrangement, chromosomal localization, and expression
      pattern of mouse guanylate cyclase activating proteins GCAP1 and GCAP2, retina
      specific Ca2+-binding proteins, and photoreceptor guanylate cyclase activators.
      METHODS: The GCAP1 and GCAP2 genes were cloned from genomic libraries and
      sequenced. The chromosomal localization of the GCAP array was determined using
      fluorescent in situ hybridization. The expression of GCAP1 and GCAP2 in mouse
      retinal tissue was determined by immunocytochemistry. RESULTS: In this study, the
      mouse GCAP1 and GCAP2 gene array, its chromosomal localization, RNA transcripts,
      and immunolocalization of the gene products were fully characterized. The GCAP
      tail-to-tail array is located at the D band of chromosome 17. Each gene is
      transcribed into a single transcript of 0.8 kb (GCAP1) and 2 kb (GCAP2).
      Immunocytochemistry showed that both GCAP genes are expressed in retinal
      photoreceptor cells, but GCAP2 was nearly undetectable in cones. GCAP2 was also
      found in amacrine and ganglion cells of the inner retina. Light-adapted and dark
      adapted retinas showed no significant difference in the distribution of the most
      intense GCAP2 staining within the outer segment and outer plexiform layers.
      CONCLUSIONS: Identical GCAP gene structures and the existence of the tail-to-tail
      gene array in mouse and human suggest an ancient gene duplication-inversion event
      preceding mammalian diversification. Identification of both GCAPs in synaptic
      regions, and of GCAP2 in the inner retina suggest roles of these Ca-binding
      proteins in addition to regulation of phototransduction.

PMID- 9579468
TI  - Functional analysis of the promoters of the human red and green visual pigment
      genes.
AB  - PURPOSE: To delineate cis-acting DNA elements involved in the expression of the
      human red and green visual pigment genes and to correlate these with
      transcription factor binding sites. METHODS: Assays of promoter activity were
      accomplished by transient transfection into WERI cells. Nested deletion and block
      mutagenesis were undertaken to delineate critical elements. Transcription factor
      binding sites were determined by DNase I footprinting and electrophoretic
      mobility shift (EMSA) analyses. RESULTS: The human retinoblastoma cell line WERI,
      but not Y-79, was found to express the red and green pigment genes. Transfection
      assays in WERI cells revealed that the proximal region of the red pigment gene
      promoter had positive (-130 to -113 and -96 to -23) and negative (-190 to -130
      and - 113 to -96) regulatory elements. The green pigment gene promoter was found
      to be 2 to 4 times more active than was that of the red pigment. This difference
      in activity was attributable mainly to a T to C substitution at position -3.
      DNase I protection and EMSA studies demonstrated the binding of several
      ubiquitous and WERI-enriched proteins to DNA sequences between - 130 and the TATA
      box. The locus control region (LCR) did not have any enhancer activity in
      transient transfection. CONCLUSIONS: The WERI cell line is a good model system
      for the analysis of gene expression of the human cone visual pigment genes. The
      expression of these genes in a cell-specific fashion seems to be controlled
      mainly by positive-acting elements in the region between - 130 and the TATA box.
      The higher activity of the green pigment gene promoter could have evolved to
      compensate for its longer distance from the activating LCR than that of the red
      pigment gene promoter (approximately 34 versus 3.5 kb). Although the LCR does not
      enhance transcription in transient transfection, it binds factors that also
      recognize the proximal promoter region. These interactions may be important for
      the establishment of a transcriptionally active domain in a chromatin context.

PMID- 9579469
TI  - Reduction of corneal edema in endotoxin-induced uveitis after application of L
      NAME as nitric oxide synthase inhibitor in rats by iontophoresis.
AB  - PURPOSE: To investigate the involvement of the cornea during endotoxin-induced
      uveitis (EIU) in the rat and the effect of Ngamma-nitro-L-arginine methyl ester
      (L-NAME) as nitric oxide synthase (NOS) inhibitor, administered by iontophoresis.
      METHODS: EIU was induced in Lewis rats that were killed at 8 and 16 hours after
      lipopolysaccharide (LPS) injection. The severity of uveitis was evaluated
      clinically at 16 hours, and nitrite levels were evaluated in the aqueous humor at
      8 hours. Corneal thickness was measured, 16 hours after LPS injection, on
      histologic sections using an image analyzer. Transmission electron microscopy
      (TEM) was used for fine analysis of the cornea. Transcorneoscleral iontophoresis
      of L-NAME (100 mM) was performed either at LPS injection or at 1 and 2 hours
      after LPS injection. RESULTS: At 16 hours after LPS injection, mean corneal
      thickness was 153.7+/-5.58 microm in the group of rats injected with LPS (n=8)
      compared with 126.89+/-11.11 microm in the saline-injected rats (n=8) (P < 0.01).
      TEM showed stromal edema and signs of damage in the endothelial and epithelial
      layers. In the group of rats treated by three successive iontophoreses of L-NAME
      (n=8), corneal thickness was 125.24+/-10.36 microm compared with 146.76+/-7.52
      microm in the group of rats treated with iontophoresis of saline (n=8),
      (P=0.015). TEM observation showed a reduction of stromal edema and a normal
      endothelium. Nitrite levels in the aqueous humor were significantly reduced at 8
      hours by L-NAME treatment (P=0.03). No effect on corneal edema was observed after
      a single iontophoresis of L-NAME at LPS injection (P=0.19). Iontophoresis of
      saline by itself induced no change in corneal thickness nor in TEM structure
      analysis compared with normal rats. CONCLUSIONS: Corneal edema is observed during
      EIU. This edema is significantly reduced by three successive iontophoreses of L
      NAME, which partially inhibited the inflammation. A role of nitric oxide in the
      corneal endothelium functions may explain the antiedematous effect of L-NAME.

PMID- 9579470
TI  - Differentiation-dependent expression of alpha-2,3-sialyltransferase in rabbit
      corneal epithelium.
AB  - PURPOSE: Lectin studies have shown that in the rabbit corneal epithelium, alpha
      2,3 sialylation of O-linked glycans differentiates limbal and corneal epithelial
      cell phenotypes. Because sialic acid can be regulated at the level of the
      expression of sialyltransferases (STs), the purpose of the present study was to
      analyze the expression of alpha-2,3STs in this tissue. METHODS: Reverse
      transcription-polymerase chain reaction (RT-PCR) was used to generate ST cDNA
      from total rabbit corneal epithelium RNA using primers selected from the
      sequences of three previously cloned STs capable of catalyzing the transfer of
      sialic acid to O-linked oligosaccharides, human placental Galbeta-1,3GalNAc
      Galbeta-1,4GluNAcalpha-2,3ST (STZ), and mouse brain Galbeta-1,3GalNAcalpha-2,3ST
      types I and II (ST3Gal I and ST3Gal II). Tissue distribution of mRNA was assayed
      by fluorescent in situ hybridization. A synthetic peptide whose sequence was
      deduced from a cloned cDNA fragment was synthesized and used to prepare an anti
      ST goat antiserum. The molecular weights of immunodetectable polypeptides and
      their distribution in cryostat sections of the limbocorneal area were
      investigated by western blot analysis and indirect immunofluorescence,
      respectively. RESULTS: RT-PCR yielded cDNA of expected basepair length for STZ
      and ST3(Gal II. The rabbit STZ cDNA was 86% identical with its human equivalent.
      Its mRNA was confined to the cornea, mainly in basal epithelial cells, and was
      not expressed in the limbus. Western blot analysis identified a band at 37 kDa
      whose binding was abolished by preincubation of the antiserum with the
      immunization peptide. Immunohistologic analysis revealed the presence of
      immunoreactive epitopes in all basal cells of the cornea but not in the limbus.
      CONCLUSIONS: STZ mRNA and the enzyme itself are expressed in the basal layer of
      the corneal epithelium but are absent in the limbus. This enzyme's de novo
      expression seems thus responsible for the differential expression of alpha-2,3
      sialylation along the limbocorneal differentiation axes. At least one more alpha
      2,3ST is also present in the epithelium.

PMID- 9579471
TI  - Expression of gelatinases A and B, and TIMPs 1 and 2 during corneal wound
      healing.
AB  - PURPOSE: To determine the expression of gelatinases A and B and the localization
      of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 during the early
      stages of corneal wound healing in rats. METHODS. One eye each of 30 adult
      Sprague-Dawley rats was treated with excimer laser keratectomy; the other eye was
      untreated. Frozen sections of corneas obtained 6, 18, and 24 hours and 3 and 7
      days after wounding were used to perform immunoconfocal microscopy and in situ
      hybridization. RESULTS: Gelatinase B was immunolocalized to the basement membrane
      zone and superficial stroma, and its mRNA was exclusively localized to basal
      epithelial cells migrating across the wound at 18 and 24 hours and 3 days after
      wounding. Tissue inhibitor of metalloproteinase-1 was also immunolocalized to the
      basement membrane zone and superficial stroma at the same time points. Gelatinase
      A was immunolocalized to the epithelium and stroma of normal corneas and was
      predominant in the basal epithelium and superficial stroma at 3 and 7 days after
      wounding. In situ hybridization confirmed gelatinase A expression by the
      epithelial cells and the stromal keratocytes. Tissue inhibitor of
      metalloproteinase-2 was immunolocalized to the epithelium in normal and wounded
      corneas. Intense TIMP-2 labeling of the basement membrane zone was noted 3 days
      after wounding. CONCLUSIONS: Unlike gelatinase A, gelatinase B is expressed
      exclusively by migrating basal epithelial cells after wounding. The matrix
      metalloproteinase-tissue inhibitor of metalloproteinase (MMP)/TIMP systems may
      play an important role in the early stages of corneal wound healing after excimer
      laser keratectomy.

PMID- 9579472
TI  - Area and depth of surfactant-induced corneal injury correlates with cell death.
AB  - PURPOSE: In previous studies in which in vivo confocal microscopy (CM) was used,
      quantifiable differences were identified in the corneal epithelium and stroma for
      surfactants producing different degrees of ocular irritation. In the present
      study, in vivo confocal microscopy was used to determine area and depth of the
      initial corneal changes, and the correlation of the data to cell death was
      characterized by ex vivo live-dead assay. METHODS: In four groups of rabbits (12
      animals each), 10 microl surfactants known to produce slight, mild, moderate, or
      severe irritation was applied to the central cornea of one eye; 4 untreated
      rabbits served as controls. Measurements of group total mean epithelial
      thickness, epithelial cell area, and depth of keratocyte loss in four corneal
      regions were made by in vivo CM in 6 rabbits of each group and in 4 control
      animals at 3 hours and in the remaining rabbits at 3 hours and 1 day. Corneas
      were then removed and fixed for conventional histologic examination (two
      eyes/treatment/group), or regions were excised and placed in culture media
      containing 2 microM calcein-acetoxymethyl ester (calcein-AM) and 4 microM
      ethidium homodimer. Using laser scanning CM, the number of dead epithelial or
      stromal cells in a 300 x 300 x 170 microm (in the x, y, and z axes, respectively)
      volume of the cornea was determined. RESULTS: Confocal microscopy showed that
      application of the slight irritant resulted in decreased epithelial thickness at
      3 hours (41.2+/-2.6 microm in treated eyes versus 43.6+/-3 microm in control
      eyes; n=6 and 4, respectively) and a significant decrease (P < 0.001) in
      epithelial cell size (630+/-203 microm2 versus 1427.2+/-90.7 microm2). On day 1,
      mild, moderate, and severe irritants caused complete loss of epithelium and
      disappearance of keratocytes to a depth of 30.8+/-10.7 microm, 47.2+/-10.4
      microm, and 764.6+/-159.6 microm (n=6, 5, and 6), respectively. At 3 hours, live
      dead assay detected more dead epithelial cells as a percentage of total surface
      cells (49.2+/-4.5% in slightly irritated eyes versus 20.9+/-3.2% in control
      eyes), significantly correlating with the measurement by in vivo CM of average
      epithelial cell size in each eye (r=-0.96; P < 0.005). On day 1, mild and
      moderate irritants showed increasing stromal cell death from 9.8+/-16.2 cells to
      36.4+/-17.7 cells, which significantly correlated with the depth of stromal
      injury determined by in vivo CM (r=0.79; P < 0.00001). No surviving keratocytes
      were detected in severely irritated eyes. CONCLUSIONS: The data support the
      hypothesis that differences in surfactant-induced ocular irritation are directly
      related to area and depth of acute corneal injury.

PMID- 9579473
TI  - Multifocal topographic visual evoked potential: improving objective detection of
      local visual field defects.
AB  - PURPOSE: To investigate the relationships between the pattern stimulation of
      different parts of the visual field (up to 25 degrees of eccentricity), the
      electrode position, and the cortical response to improve objective detection of
      local visual field defects. METHODS: The human visual evoked potential (VEP) was
      assessed using multifocal pseudorandomly alternated pattern stimuli that were
      cortically scaled in size. Monopolar and bipolar electrode positions were used.
      The visual field was investigated up to 26 degrees of eccentricity. Twelve normal
      subjects and seven subjects with visual field defects of different nature were
      studied. RESULTS: Although the monopolar response is heavily biased toward the
      lower hemifield, bipolar leads overlying the active occipital cortex (straddling
      the inion) demonstrate good signals from all areas of the visual field tested.
      The amplitude is almost equal for the averaged upper and lower hemifields, but
      the polarity is opposite, causing partial cancellation of the full-field VEP. The
      degree of cancellation depends mainly on latency differences between the vertical
      hemifields. The bipolar VEP corresponded well with Humphrey visual field defects,
      and it showed a loss of signal in the scotoma area. CONCLUSIONS: The multifocal
      VEP demonstrates good correspondence with the topography of the visual field.
      Recording with occipital bipolar electrode placement is superior to standard
      monopolar recording. To avoid a full-field cancellation effect, a separate
      evaluation of upper and lower hemifields should be used for the best assessment
      of retinocortical pathways. This technique represents a significant step toward
      the possible application of the multifocal VEP to objective detection of local
      defects in the visual field.

PMID- 9579475
TI  - Ultrastructural changes and immunocytochemical localization of microtubule
      associated protein 1 in guinea pig optic nerves after acute increase in
      intraocular pressure.
AB  - PURPOSE: To investigate ultrastructural changes and localization of microtubule
      associated protein 1 (MAP 1) in optic nerves of guinea pigs in conditions of
      acute increase in intraocular pressure (IOP). METHODS: Intraocular pressure was
      increased acutely in 40 guinea pig eyes, and 40 eyes were examined in 20 normal
      control animals. Analytic methods included quick-freezing and deep-etching (QF
      DE) and conventional fixation. Microtubule-associated protein 1
      immunocytochemistry was performed. RESULTS: In conventional ultrathin sections,
      an alteration of the axoplasmic ultrastructure was seen only at the level of the
      lamina cribrosa sclerae. The number of microtubules was significantly decreased
      in the axoplasm that exhibited accumulations of membranous organelles. Cross
      bridged filaments on microtubules were significantly reduced in number when
      determined by the QF-DE method. The immunostaining of tubulin or MAP 1 was less
      positive than in other samples with normal IOP, revealed by light microscopic
      immunocytochemistry. Immunoelectron microscopy demonstrated that MAP 1 was
      significantly decreased in the axoplasm that showed accumulations of membranous
      organelles. CONCLUSIONS: The acute alteration of axoplasmic ultrastructures in
      some parts of the optic nerves at the level of the lamina cribrosa involves a
      decrease in the amount of MAP 1 and a decrease in the number of axonal cross
      bridges on microtubules in a condition of acutely increased IOP, which could be
      related to microtubule instability and abnormal organelle transport in the
      axoplasm.

PMID- 9579474
TI  - Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice.
AB  - PURPOSE: To characterize ocular abnormalities associated with iris atrophy in
      DBA/2J mice and to determine whether mice of this strain develop elevated
      intraocular pressure (IOP) and glaucoma. METHODS: Different approaches, including
      slit-lamp biomicroscopy, ophthalmoscopic examination, ultrasound backscatter
      microscopy, and histology were used to examine the eyes of DBA/2J mice ranging
      from 2 to 30 months old. IOP was measured in DBA/2J mice of different ages.
      RESULTS: DBA/2J mice were found to develop pigment dispersion, iris
      transillumination, iris atrophy, anterior synechias, and elevated IOP. IOP was
      elevated in most mice by the age of 9 months. These changes were followed by the
      death of retinal ganglion cells, optic nerve atrophy, and optic nerve cupping.
      The prevalence and severity of these lesions increased with age. Optic nerve
      atrophy and optic nerve cupping was present in the majority of mice by the age of
      22 months. CONCLUSIONS: DBA/2J mice develop a progressive form of secondary angle
      closure glaucoma that appears to be initiated by iris atrophy and the associated
      formation of synechias. This mouse strain represents a useful model to evaluate
      mechanisms of pressure-related ganglion cell death and optic nerve atrophy, and
      to evaluate strategies for neuroprotection.

PMID- 9579476
TI  - Neurotoxic effects of low doses of glutamate on purified rat retinal ganglion
      cells.
AB  - PURPOSE: To determine whether low concentrations of glutamate induce cell death
      in purified rat retinal ganglion cells (RGCs). METHODS: Rat retinal ganglion
      cells were purified from dissociated retinal cells by a modified two-step panning
      method and were cultured in serum-free medium containing neurotrophic factors and
      forskolin. Survival of RGCs after exposure to glutamate, with or without
      glutamate receptor antagonists, was measured by calcein-acetoxymethyl ester
      staining after 3 days in culture. To visualize calcium signals, RGCs were loaded
      with the calcium indicator dye, fluo-3 acetoxymethyl ester, and fluorescence was
      measured by laser scanning confocal microscope. Electrophysiological properties
      of RGCs were examined by using the whole-cell, patch-clamp technique. RESULTS:
      The application of increasing concentrations (5-500 microM) of glutamate caused a
      dose-dependent increase in RGC death after 3 days in culture. Neurotoxic effects
      of low doses of glutamate were totally blocked by a specific alpha-amino-3
      dihydro-5-methyl-isoxazol-4-propionic acid-kainate (AMPA-KA) receptor antagonist,
      6,7-dinitroquinoxaline-2,3-dione (DNQX), but not by a specific N-methyl-D
      aspartate receptor antagonist, 2-amino-5-phosphonovalerate (APV). In addition,
      calcium imaging and patch-clamp recordings showed that intracellular calcium
      accumulation and glutamate-evoked inward currents were completely blocked by DNQX
      but not by APV. CONCLUSIONS: Low doses of glutamate can activate AMPA-KA
      receptors in RGCs, which causes increases in intracellular calcium and decreases
      in cell survival. This is the first report to show the functional role of calcium
      permeable AMPA-KA receptors in cultured RGCs.

PMID- 9579477
TI  - Costimulatory molecules in ocular cicatricial pemphigoid.
AB  - PURPOSE: To examine normal and inflamed conjunctiva from patients with ocular
      cicatricial pemphigoid (OCP) for the presence of costimulatory molecule CD28 and
      its ligands B7-1 (CD80) and B7-2 (CD86). METHODS: Conjunctival biopsy specimens
      from 12 patients with OCP and from five healthy persons undergoing cataract
      surgery were analyzed by light microscopy and immunohistochemical examination
      with monoclonal antibody probes for CD28, B7-1, and B7-2 molecules and for
      mononuclear cell subtypes. RESULTS: Epithelium of OCP conjunctiva showed more
      Langerhans' cells, B7-1-positive (+) cells, and B7-2 expression (ratio of B7-2
      positive cells to antigen-presenting cells). In the substantia propria, OCP
      specimens showed significantly increased numbers of T cells (CD3 +), macrophages
      (CD68+), CD28+ cells, B7-2+ cells (CD86+), Langerhans' cells (CD1a), and B7-1+
      cells (CD80). Most of the B7-2+ cells, macrophages, and Langerhans' cells were
      located subepithelially. B7-2 expression was significantly higher in OCP
      conjunctival substantia propria compared with normal conjunctiva. CONCLUSIONS:
      The results of this study indicate that the expression of the costimulatory
      molecule B7-2 is upregulated in conjunctiva of patients with active OCP. This
      increased subepithelial B7-2 expression may contribute to the sustained immune
      activation in OCP conjunctiva.

PMID- 9579478
TI  - A small molecular weight factor in aqueous humor acts on C1q to prevent antibody
      dependent complement activation.
AB  - PURPOSE: Aqueous humor inhibits activation of the classic complement pathway;
      however, the mechanism of this inhibition is unknown. We have examined at the
      molecular level potential factors responsible for the inhibition, and we have
      tried to determine where in the complement pathway the inhibition takes place.
      METHODS: Fresh rabbit aqueous humor was size fractionated by centrifuge
      concentrators and by size exclusion column chromatography, and each fraction was
      assayed for inhibition of the classic complement pathway in a standard CH50
      hemolytic assay. Fractions with inhibitory activity were assayed for protein and
      the presence of ascorbic acid and were subjected to heat treatment. To identify
      where in the pathway the inhibitor(s) function, the expression of activated
      complement components bound to the surface of antibody-coated erythrocytes was
      analyzed by flow cytometry using fluorescein isothiocyanate-labeled antibodies to
      specific complement components. In addition, hemolytic assays were performed for
      the function of individual complement components. RESULTS: The most potent
      inhibition of the classic pathway was in a fraction of aqueous humor of less than
      1.3 kDa. The inhibitory activity in the fraction was unassociated with detectable
      protein or ascorbic acid, and it remained present after heat treatment. The
      functional analysis through flow cytometry and hemolytic assays for individual
      complement components showed that the inhibitor in the less than 1.3-kDa fraction
      caused a blockade in the complement pathway at the level of C1q. CONCLUSIONS: The
      aqueous humor contains a unique potent anticomplementary factor that has a
      molecular weight less than 1.3 kDa. This heat-stable inhibitory factor inhibits
      the classic pathway at the level of C1q. These results imply that within the eye
      the complement pathway is inhibited at the earliest steps of its initiation. Such
      inhibition would prevent production of complement products that mediate
      inflammation and chemotaxis of inflammatory cells. Therefore, as part of the
      adaptation of immune privilege, the ocular microenvironment is protected from
      inflammation induced by antigen-antibody complexes.

PMID- 9579479
TI  - Increased frequencies of interleukin-2- and interferon-gamma-producing T cells in
      patients with active Behcet's disease.
AB  - PURPOSE: To elucidate the profile of cytokine-producing T cells in patients with
      active or inactive Behcet's disease (BD), the frequencies of type 1 (Interleukin-
      [IL] 2, interferon-gamma [IFN-gamma]) and type 2 (IL-4) cytokine-producing CD4+
      and CD8+ cells in peripheral blood were investigated, and the effect of
      immunosuppressive drugs on the profile of cytokine-producing cells was evaluated.
      METHODS: Fifty-two patients with BD (32 with active and 20 with inactive BD) and
      33 healthy control subjects were the subjects in this study. Patients were or
      were not treated with immunosuppressive drugs. Peripheral blood mononuclear cells
      were fixed, permeabilized, and stained for intracellular cytokines in combination
      with cell surface markers CD4 and CD8 for flow cytometric analysis. RESULTS: In
      nontreated patients with BD, the frequencies of IL-2- and IFN-gamma-producing CD4
      and CD8+ cells in active patients were significantly higher than those in
      inactive patients. Conversely, the frequencies of IL-4 producing CD4+ and CD8+
      cells in nontreated patients with active BD were comparable with those in
      patients with inactive disease and in control subjects. Patients with inactive BD
      who were treated with immunosuppressive drugs showed significantly lower
      frequencies of IL-2- and IFN-gamma-producing CD4+ and CD8+ cells than did treated
      patients with active BD. CONCLUSIONS: The frequencies of type 1 cytokine
      producing CD4+ and CD8+ cells increased in patients with active BD. Effective
      immunosuppressive treatments decreased the population of type 1 cytokine
      producing CD4+ and CD8+ cells. These results suggest that type 1 cytokine
      producing cells play an important role in the immunopathogenesis of the
      inflammation in BD.

PMID- 9579480
TI  - Inductive pathways leading to rat tear IgA antibody responses.
AB  - PURPOSE: To define the inductive pathways leading to rat tear IgA antibody
      responses. METHODS: Fluoresceinated dinitrophenylated bovine serum albumin was
      encapsulated in poly(lactide-co-glycolide) microparticles and was administered by
      intranasal, ocular topical, or gastrointestinal routes. Histologic methods were
      used to determine the microparticles' ability to access tissues associated with
      mucosal inductive pathways. Rats were immunized with microencapsulated antigen by
      intranasal or ocular topical routes. Tear IgA and serum IgG antibody
      concentrations were assessed by radioimmunoassay. The frequency of antibody
      secreting cells in tissues, postulated to function in tear IgA induction, was
      measured by enzyme-linked immunospot assay. RESULTS: Although uptake of
      microencapsulated antigen was greatest at the site of delivery, ocular topical
      administration resulted in antigen uptake in the conjunctiva and in nasal
      associated lymphoid tissue. Intranasal immunization resulted in earlier and
      significantly higher tear IgA and serum IgG antibody responses and in higher
      frequencies of antibody-secreting cells in corresponding draining cervical lymph
      nodes and lacrimal glands than did ocular topical immunization. CONCLUSIONS:
      Nasal-associated lymphoid tissue functions as a primary inductive site for tear
      IgA antibody responses by contributing triggered IgA-committed B cells to the
      lacrimal gland.

PMID- 9579481
TI  - Role of protein tyrosine kinase on regulation of trabecular meshwork and ciliary
      muscle contractility.
AB  - PURPOSE: Trabecular meshwork and ciliary muscle express properties of smooth
      muscle cells. The contractility of trabecular meshwork and ciliary muscle is
      differently modulated by various agents. To reveal contractile regulatory
      processes, the effects of activation and inhibition of protein tyrosine kinases
      (PTKs) and their interaction with other protein kinases on contractility were
      measured. METHODS: Measurements of isometric tension were performed on isolated
      bovine trabecular meshwork and ciliary muscle strips using a custom-built,
      electromagnetic, force-length transducer. Protein tyrosine kinase (PTK) was
      stimulated by epidermal growth factor (EGF) and was inhibited by genistein or
      tyrphostin 51. Protein kinase C (PKC) was inhibited by chelerythrine or NPC-15437
      and protein kinases A and G (PKA-PKG) by H8. RESULTS: Isolated strips were
      precontracted by applying carbachol 10(-6) M for 30 minutes (100% carbachol
      maximum contraction). Inhibition of PTK evoked a maximum relaxation of 79.2+/
      4.2% in trabecular meshwork and of 38.1+/-3.1% in ciliary muscle (n=8).
      Inhibition of PKC or PKA-PKG induced relaxations only in trabecular meshwork.
      When PTK and PKC or PKA-PKG were inhibited, the relaxation induced by inhibition
      of PTK was additive to inhibition of the other protein kinases. Stimulation of a
      receptor with PTK activity by EGF induced a relaxation in trabecular meshwork and
      a contraction in ciliary muscle precontracted by carbachol. When trabecular
      meshwork and ciliary muscle were activated by EGF, inhibition of PTK by genistein
      relaxed the cell preparations. CONCLUSIONS: Inhibition of PTK induces more
      prominent relaxation in trabecular meshwork than in ciliary muscle. The effects
      of inhibition of PTK on relaxation are independent of inhibition of PKC and PKA
      PKG. The signaling cascade after activation of a tyrosine kinase receptor by EGF
      is differently modulated in trabecular meshwork and ciliary muscle. The effect of
      genistein on relaxation is probably not directly related to the EGF receptor. PTK
      inhibitors are possible agents for the development of novel antiglaucoma drugs.

PMID- 9579482
TI  - Transplantation of retinal pigment epithelial cells and immune response in the
      subretinal space.
AB  - PURPOSE: To evaluate the fate of retinal pigment epithelial cell (RPE) allografts
      in the subretinal space. METHODS: Transplantation was performed in Royal College
      of Surgeons (RCS) rats. Two rat strains, BD IX and LEJ, which have incompatible
      major histocompatibility complex (MHC) haplotypes, were selected as healthy RPE
      donors. Transplantation was performed when recipients were 19 to 21 days old.
      Host systemic immunity was enhanced by challenge with donor spleen cells 2 weeks
      after RPE transplantation. Control subjects were administered injections of
      saline or host spleen cells. The animals were killed at 3 or 5 months of age. The
      extent of photoreceptor rescue was determined by counting the maximum layers of
      surviving photoreceptor nuclei in histologic sections. Reverse transcription
      polymerase chain reaction analysis of the grafts was performed with host- and
      donor-specific primers. RESULTS: Despite the absence of acute immune rejection,
      chronic rejection occurred and was evidenced by an increased loss of
      photoreceptor cells in immunologically challenged RCS rats. Grafts with disparity
      at MHC class I and class II lost their ability to rescue photoreceptor cells more
      readily than did grafts with disparity at MHC class II alone. Furthermore, the
      donor RPE cells that were normally MHC class II-negative expressed MHC class II
      mRNA in the subretinal space after transplantation. CONCLUSIONS: Systemic
      immunity appeared to exert a slow but significant influence in the subretinal
      space. Therefore, in planning future trials involving human subjects, the
      immunologically privileged status of the subretinal space should be regarded as
      imperfect.

PMID- 9579483
TI  - Hypoxia and vascular endothelial growth factor stimulate angiogenic integrin
      expression in bovine retinal microvascular endothelial cells.
AB  - PURPOSE: Integrins alphavbeta3 and alphavbeta5 are cell-to-matrix adhesion
      molecules that have been reported to mediate vascular cell proliferation and
      migration. The authors investigated the regulation of expression of these
      angiogenic integrins by hypoxia and vascular endothelial growth factor (VEGF) in
      retinal microvascular endothelial cells in culture. METHODS: Cultured bovine
      retinal capillary endothelial cells were exposed to human recombinant VEGF under
      normoxic (95% air, 5% CO2) conditions to assess the effects of VEGF. Hypoxia
      studies were performed under lower oxygen concentration (0.5%-1.5% O2) induced by
      nitrogen replacement in constant 5% CO2 conditions. Integrin family mRNA and
      protein expression were assessed by northern blot analysis and
      immunoprecipitation. RESULTS: VEGF (25 ng/ml) increased integrin alphav, beta3,
      and 35 mRNA after 24 hours 6.1+/-0.8-fold (P < 0.001), 5.9+/-1.1-fold (P <
      0.001), and 1.9+/-0.2-fold (P < 0.01), respectively. Similarly, hypoxia
      stimulated gene expression of integrin alphav and beta3 after 24 hours by 5.1+/
      1.7-fold (P < 0.01) and 3.0+/-0.5-fold (P < 0.01), respectively, and integrin
      beta5 after 9 hours 1.4+/-0.2-fold (P < 0.05). This hypoxia-induced, integrin
      alphav mRNA elevation was inhibited significantly by anti-VEGF neutralizing
      antibody. Also, a conditioned medium from confluent endothelial cells maintained
      under hypoxic conditions for 24 hours produced a 7.1+/-1.1-fold increase (P <
      0.001) in integrin alphav mRNA expression after 24 hours, which was reversed by
      anti-VEGF neutralizing antibody. Induction of integrin alphav by VEGF and hypoxia
      was confirmed in the protein level. CONCLUSIONS: These data suggest that hypoxia
      stimulates expression of vascular integrins alphavbeta3 and alphavbeta5 in
      retinal microvascular endothelial cells partially through autocrine-paracrine
      action of VEGF induced by the hypoxic state.

PMID- 9579484
TI  - Transgenic mice expressing a functional human photopigment.
AB  - PURPOSE: Changes in retinal photopigments represent a fundamental step in the
      evolution of visual systems, in that addition of new pigment types or alterations
      in the spectral absorption properties of existing pigments modify visual
      capacities and thus open new visual worlds. To provide a tool that would allow
      direct examination of the changes caused by the presence of novel photopigments,
      this study was designed to determine whether a gene encoding a human cone
      photopigment introduced into the mouse genome would be expressed in a cone
      specific manner and would support phototransduction. METHODS: Mice transgenic for
      the human long wavelength-sensitive (L) photopigment were generated by
      microinjection of fertilized mouse eggs. RNA expression in different tissues was
      monitored by reverse transcription-polymerase chain reaction analysis.
      Photopigment protein was localized in retinal cross sections and wholemounts by
      antibody staining. Light transduction of the cone photopigments was assessed by
      flicker photometric electroretinography (ERG). RESULTS: The human transgene was
      expressed specifically in the mouse cones in quantities comparable to those of
      the mouse middle wavelength-sensitive (M) pigment gene. Immunocytochemical
      analysis showed that the human L pigment was abundantly synthesized in most mouse
      cones, was translocated to the outer segments, and caused no detectable cone
      degeneration. Electroretinographic spectral sensitivity analysis showed that the
      human L pigment was efficient in eliciting an electrical response. The degree of
      expression of the transgene in the two founders correlated well with the spectral
      responsivity of the ERG. CONCLUSIONS: The human L photopigment transduces light
      efficiently in mouse cones, implying that all protein domains necessary for
      efficient interaction with intracellular transport and signal transduction
      machineries in mouse cones have been conserved through evolution. The expression
      of the human L photopigment gene in both classes of cone of the mouse retina
      indicates that the transgene did not have the regulatory elements necessary for
      restricting its expression to mouse M cones or that such elements are not
      recognized in mouse UV-sensitive cones.

PMID- 9579485
TI  - Parvalbumin, a horizontal cell-associated calcium-binding protein in
      retinoblastoma eyes.
AB  - PURPOSE: To search for differentiation in retinoblastoma toward horizontal cells
      and retinal neurons other than photoreceptor cells with antibodies to
      parvalbumin, a horizontal, ganglion, and amacrine cell-associated antigen.
      METHODS: Fifty formalin-fixed and paraffin-embedded human eyes with an
      intraocular retinoblastoma and two orbital recurrences were studied using the
      avidin-biotinylated peroxidase complex method and monoclonal antibody (mAb) PA
      235 to parvalbumin. RESULTS: In the retinas of retinoblastoma eyes obtained after
      birth, horizontal cells at the outer border of the inner nuclear layer and their
      processes in the inner part of the outer plexiform layer always reacted with mAb
      PA-235. Immunolabeled ganglion and amacrine cells were found, respectively, in 31
      (76%; 95% confidence interval [CI] 60-88) and 15 (37%; 95% (CI 22-53) of the 41
      eyes with preserved retinas, whereas bipolar and photoreceptor cells were
      unlabeled. Undifferentiated and differentiated retinoblastoma cells in all
      studied specimens were negative for parvalbumin. However, immunopositive
      horizontal and ganglion cells engulfed by the tumor were present within 36 of the
      50 retinoblastomas (72%; 95% CI 58 - 84), which often allowed the tracing of
      otherwise invisible remnants of former infiltrated retinas. CONCLUSIONS:
      Parvalbumin is a useful marker for horizontal and ganglion cells in normal and
      pathologic human retinas, including those entrapped within retinoblastoma. The
      absence of parvalbumin from tumor cells argues against differentiation similar to
      that seen in these parvalbumin-positive neurons and subpopulations of amacrine
      cells from the second trimester onward.

PMID- 9579486
TI  - Number of perifoveal vessels in aging, hypertension, and atherosclerosis: the
      Rotterdam Study.
AB  - PURPOSE: To assess the associations among age, gender, hypertension,
      atherosclerosis, combined hypertension and atherosclerosis, and the number of
      perifoveal retinal arterioles and venules in the general elderly population.
      METHODS: A cross-sectional study was performed among subjects ranging in age from
      55 to 74 years who participated in the population-based Rotterdam Study.
      Perifoveal vessels were counted in a masked way by two observers within 1500
      microm from the foveola on fundus transparencies of 34 cases with hypertension,
      55 with lower extremity arterial disease (LEAD), 27 with hypertension and LEAD,
      and 194 control subjects without either condition. Multiple linear regression
      analysis was used to study the associations. RESULTS: The mean number of
      perifoveal vessels was 12.0 (SD 2.0). The number of perifoveal vessels decreased
      with age in all groups, with an average of 0.4 per 5 years (95% confidence
      interval [CI], 0.2, 0.6, P=0.001). In women, the number of perifoveal vessels was
      on average 0.8 (95% CI, 0.3, 1.2, P=0.002) lower than in men. Patients with
      hypertension had a significantly lower number of vessels compared with control
      subjects: mean reduction 1.0 (95% CI, 0.2, 1.7), independent of age and sex.
      Patients with LEAD had 1.0 (95% CI, 0.4, 1.6) fewer perifoveal vessels, whereas
      the number in those with hypertension and LEAD was 1.8 (95% (CI, 1.0, 2.6) lower.
      Additional adjustment for established cardiovascular risk factors did not
      materially alter the findings. CONCLUSIONS: Increasing age, female gender,
      systemic hypertension, and LEAD were associated with a lower number of perifoveal
      arterioles and venules in the elderly.

PMID- 9579487
TI  - Age-related lipid oxidation in human lenses.
AB  - PURPOSE: To quantify age-related changes in products of lipid oxidation in human
      lenses and to relate these changes to membrane hydrocarbon chain structure.
      Deviation from a well-defined membrane-lipid composition and structure could
      result in alterations in membrane function and disruption of the homeostasis of
      the cell. METHODS: Infrared spectroscopy was used to detect lipid compositional
      and structural changes in human lens membranes associated with age and cataracts.
      RESULTS: Lipid oxidation increased linearly threefold relative to total
      phospholipids in subjects ranging in age between 1 and 85 years, as was evident
      by increases in trans double bonds, lipid carbonyls, and secondary products.
      There was no statistical difference between the levels of lipid oxidation in the
      cortex or nucleus. Lipid hydrocarbon chain order (rigidity) increased from
      approximately 40% at birth to 70% at 80 years of age. Changes in lipid order
      correlated with changes in the relative content of membrane phosphatidylcholine
      and sphingomyelin, and with the level of lipid oxidation. CONCLUSIONS: Lipid
      oxidation increased linearly and uniformly throughout the human lens with age.
      The change in lipid oxidation with age correlated to a change in lipid order.

PMID- 9579488
TI  - Changes in visually guided behavior of Royal College of Surgeons rats as a
      function of age: a histologic, morphometric, and functional study.
AB  - PURPOSE: To compare the changes in visually guided performance as a function of
      age between Royal College of Surgeons (RCS) dystrophic and congenic rats and to
      correlate photoreceptor cell number with visually guided performance in age
      matched populations of RCS dystrophic rats. METHODS: The visually guided
      performances of RCS dystrophic (n=6) and congenic (n=7) rats were studied from
      0.75 to 12 months of age using a water escape paradigm that tested their ability
      to find a submersed, randomly placed platform that used a light source as a clue.
      The time to find the platform (latency) was recorded. In age-matched dystrophic
      RCS rats, histopathologic changes were described and the number of photoreceptor
      cell nuclear profiles per midsagittal retinal section was counted. Changes with
      age in visually guided behavior and photoreceptor cell populations of RCS
      dystrophic rats then were compared. RESULTS: The latency of RCS dystrophic rats
      increased significantly beyond that of congenic rats after 6 months of age.
      Photoreceptor cell number in dystrophic rats precipitously decreased through 6
      months of age, stabilized at 9 months, and decreased further at 12 months. Two
      unexpected results were seen in the dystrophic animals: At 6 months of age, as
      few as 22+/-3 photoreceptor cell nuclei per midsagittal section provided similar
      latencies as at 2 months when there were as many as 400. Although the number of
      photoreceptor cells remained stable from 6 to 9 months of age, functional vision
      significantly deteriorated. CONCLUSIONS: Two important phenomena were observed.
      First, the RCS rats performed very well in the water escape test even while their
      photoreceptor cell population was being decimated. Second, once a low threshold
      was reached, a dramatic deterioration of visually guided behavior occurred
      without a further reduction in photoreceptor cell numbers.

PMID- 9579489
TI  - Memantine is neuroprotective in a rat model of pressure-induced retinal ischemia.
AB  - PURPOSE: To quantify vitreous amino acid concentrations in pressure-induced
      retinal ischemia and to evaluate the neuroprotective effect of memantine, a N
      methyl-D-aspartate (NMDA) antagonist, administered before and at two time
      intervals after ischemia. METHODS: Retinal ischemia was induced in 10 rats by
      elevating the intraocular pressure to 120 mm Hg. The concentrations of the amino
      acids of vitreous samples were measured by high-pressure liquid chromatography.
      In another series of 56 rats, ischemia was induced in a similar fashion. Fifteen
      rats received 20 mg/kg x day memantine by a subcutaneous osmotic pump starting 2
      days before ischemia, 13 rats received 10 mg/kg memantine intraperitoneally (ip)
      0.5 and 4.5 hours after reperfusion, 13 rats received 10 mg/kg memantine ip 3.5
      and 7.5 hours after reperfusion, and 15 rats received the vehicle alone. Ischemic
      damage was histologically quantified 14 days after ischemia. RESULTS: Compared
      with the nonischemic fellow eyes, there was an elevation (P < 0.05) in the mean
      vitreous concentration of glutamate (223%+/-41%) and glycine (428%+/-92%). The
      percentage of surviving neurons in the ganglion cell layer was 33%+/-3% in the
      controls, 61%+/-5% (P < 0.001) when memantine was infused subcutaneously before
      ischemia, 52%+/-5% (P < 0.05) when memantine was injected ip 0.5 and 4.5 hours
      after ischemia, and 48%+/-5% (P > 0.05) when injected ip 3.5 and 7.5 hours after
      ischemia. CONCLUSIONS: Retinal ischemia increased vitreous concentrations of
      glutamate and glycine. Both amino acids were agonists at the NMDA receptor. The
      NMDA receptor antagonist memantine reduced ganglion cell loss when given
      systemically before or within 30 minutes of retinal ischemia.

PMID- 9579490
TI  - Sensitive physiologic imaging with contrast-enhanced magnetic resonance imaging.

PMID- 9579491
TI  - Epidural anesthesia reduces the gain and maximum intensity of shivering.
AB  - BACKGROUND: Shivering can be characterized by its threshold (triggering core
      temperature), gain (incremental intensity increase), and maximum intensity. The
      gain of shivering might be preserved during epidural or spinal anesthesia if
      control mechanisms compensate for lower-body paralysis by augmenting the activity
      of upper-body muscles. Conversely, gain will be reduced approximately by half if
      the thermoregulatory system fails to compensate. Similarly, appropriate
      regulatory feedback might maintain maximum shivering intensity during regional
      anesthesia. Accordingly, the gain and maximum intensity of shivering during
      epidural anesthesia were determined. METHODS: Seven volunteers participated on
      two randomly ordered study days. On one day (control), no anesthesia was
      administered; on the other, epidural anesthesia was maintained at a T8 sensory
      level. Shivering, at a mean skin temperature near 33 degrees C, was provoked by
      central-venous infusion of cold fluid; core cooling continued until shivering
      intensity no longer increased. Shivering was evaluated by systemic oxygen
      consumption and electromyography of two upper-body and two lower-body muscles.
      The core temperature triggering an increase in oxygen consumption identified the
      shivering threshold. The slopes of the oxygen consumption versus core temperature
      and electromyographic intensity versus core temperature regressions identified
      systemic and regional shivering gains, respectively. RESULTS: The shivering
      threshold was reduced by epidural anesthesia by approximately 0.4 degrees C, from
      36.7 +/- 0.6 to 36.3 +/- 0.5 degrees C (means +/- SD; P < 0.05). Systemic gain,
      as determined by oxygen consumption, was reduced from -581 +/- 186 to -215 +/-
      154 ml x min(-1) x degrees C(-1) (P < 0.01). Lower-body gain, as determined
      electromyographically, was essentially obliterated by paralysis during epidural
      anesthesia, decreasing from -0.73 +/- 0.85 to -0.04 +/- 0.06 intensity
      units/degrees C (P < 0.01). However, upper-body gain had no compensatory
      increase: -1.3 +/- 1.1 units/degrees C control versus 2.0 +/- 2.1 units/degrees C
      epidural. Maximum oxygen consumption was decreased by one third during epidural
      anesthesia: 607 +/- 82 versus 412 +/- 50 ml/min (P < 0.05). CONCLUSIONS: These
      results confirm that regional anesthesia reduces the shivering threshold.
      Epidural anesthesia reduced the gain of shivering by 63% because upper-body
      muscles failed to compensate for lower-body paralysis. The thermoregulatory
      system thus fails to recognize that regional anesthesia reduces metabolic heat
      production, instead responding as if lower-body muscular activity remained
      intact.

PMID- 9579492
TI  - Meperidine and alfentanil do not reduce the gain or maximum intensity of
      shivering.
AB  - BACKGROUND: Thermoregulatory shivering can be characterized by its threshold
      (triggering core temperature), gain (incremental intensity increase with further
      core temperature deviation), and maximum intensity. Meperidine (a combined mu-
      and kappa-agonist) treats shivering better than equianalgesic doses of pure mu
      opioid agonists. Meperidine's special antishivering action is mediated, at least
      in part, by a disproportionate decrease in the shivering threshold. That is,
      meperidine decreases the shivering threshold twice as much as the
      vasoconstriction threshold, whereas alfentanil (a pure mu-agonist) decreases the
      vasoconstriction and shivering thresholds comparably. However, reductions in the
      gain or maximum shivering intensity might also contribute to the clinical
      efficacy of meperidine. Accordingly, we tested the hypothesis that meperidine
      reduces the gain and maximum intensity of shivering much more than alfentanil
      does. METHODS: Ten volunteers were each studied on three separate days: (1)
      control (no drug); (2) a target total plasma meperidine concentration of 1.2
      microg/ml; and (3) a target plasma alfentanil concentration of 0.2 microg/ml.
      Skin temperatures were maintained near 31 degrees C, and core temperatures were
      decreased by central-venous infusion of cold lactated Ringer's solution until
      maximum shivering intensity was observed. Shivering was evaluated using oxygen
      consumption and electromyography. A sustained increase in oxygen consumption
      identified the shivering threshold. The gain of shivering was calculated as the
      slope of the oxygen consumption versus core temperature regression, and as the
      slope of electromyographic intensity versus core temperature regression. RESULTS:
      Meperidine and alfentanil administration significantly decreased the shivering
      thresholds. However, neither meperidine nor alfentanil reduced the gain of
      shivering, as determined by either oxygen consumption or electromyography. Opioid
      administration also failed to significantly decrease the maximum intensity of
      shivering. CONCLUSIONS: The authors could not confirm the hypothesis that
      meperidine reduces the gain or maximum intensity of shivering more than
      alfentanil does. These results suggest that meperidine's special antishivering
      effect is primarily mediated by a disproportionate reduction in the shivering
      threshold.

PMID- 9579493
TI  - Isoflurane alters shivering patterns and reduces maximum shivering intensity.
AB  - BACKGROUND: Shivering can be characterized by its threshold (triggering core
      temperature), gain (incremental intensity increase with further core
      hypothermia), and maximum response intensity. Isoflurane produces a clonic
      muscular activity that is not a component of normal shivering. To the extent that
      clonic activity is superimposed on normal thermoregulatory shivering, the gain of
      shivering might be increased during isoflurane anesthesia. Conversely, volatile
      anesthetics decrease systemic oxygen consumption and peripherally inhibit
      skeletal muscle strength, which might limit maximum intensity despite central
      activation. The purpose of the present study was, therefore, to evaluate the
      effect of isoflurane shivering patterns and the gain and maximum intensity of
      shivering. METHODS: Ten volunteers were each studied in two separate protocols:
      (1) control (no drug) and (2) 0.7% end-tidal isoflurane. On each day, the mean
      skin temperature was maintained at 31 degrees C. Core temperature was then
      reduced by infusion of cold fluid until shivering intensity no longer increased.
      The core temperature triggering the initial increase in oxygen consumption
      defined the shivering threshold. The gain of shivering was defined by the slope
      of the core temperature versus oxygen consumption regression. Pectoralis and
      quadriceps electromyography was used to evaluate anesthetic-induced facilitation
      of clonic (5-7 Hz) muscular activity. RESULTS: Isoflurane significantly decreased
      the shivering threshold from 36.4 +/- 0.3 to 34.2 +/- 0.8 degrees C. The increase
      in oxygen consumption was linear on the control day and was followed by sustained
      high-intensity activity. During isoflurane administration, shivering was
      characterized by bursts of intense shivering separated by quiescent periods.
      Isoflurane significantly increased the gain of shivering (as calculated from the
      initial increase), from -684 +/- 266 to -1483 +/- 752 ml x min(-1) x degrees C(
      1). However, isoflurane significantly decreased the maximum intensity of
      shivering, from 706 +/- 144 to 489 +/- 80 ml/min. Relative electromyographic
      power in frequencies associated with clonus increased significantly when the
      volunteers were given isoflurane. CONCLUSIONS: These data indicate that
      isoflurane anesthesia markedly changes the overall pattern of shivering during
      progressive hypothermia from a linear increase to an unusual saw-tooth pattern.
      They further suggest that clonic muscular activity combines with shivering to
      increase the initial gain of shivering during isoflurane anesthesia, but that
      isoflurane peripherally inhibits the maximum expression of shivering.

PMID- 9579494
TI  - Pharmacokinetic analysis of the effect of vecuronium in surgical patients:
      pharmacokinetic and pharmacodynamic modeling without plasma concentrations.
AB  - BACKGROUND: Methods of the kinetic analysis of vecuronium based on effect only
      were developed but have been limited by the short time period of the studies.
      Using a multicompartment model and sequential dosing, the authors studied the
      ability of tests to determine most pharmacokinetic and pharmacodynamic parameters
      of vecuronium without measuring plasma concentrations. METHODS: The time course
      of neuromuscular blockade by successive bolus doses of vecuronium was recorded
      using electromyography. Inhibition of neuromuscular transmission by vecuronium
      was modeled by a biexponential decline in the concentrations in the central
      compartment and first-order transfer between the central and the effect
      compartments responsible for the inhibition of the first (T1) and fourth (T4)
      responses to train-of-four stimulation. RESULTS: The time course of the effect of
      vecuronium was described well by the model. The mean half-lives of equilibration
      between plasma and the effect compartments to inhibit T1 and T4 were 2.5 and 3.2
      min, respectively. The mean half-lives of distribution and elimination from the
      central compartment were 7.7 and 7.8 min, respectively. From the kinetic and
      dynamic parameters calculated after two and three doses, the time taken to
      recover to 50% of the maximal block of T1 was predicted for the succeeding dose.
      The mean prediction errors (100 x [absolute difference between actual and
      predicted times]/actual) were 13.6% (range, 0-40%) and 15% (range, 0-25%) after
      three and four doses, respectively. CONCLUSIONS: After sequential doses,
      measurement of the time course of the effect of vecuronium yields pharmacokinetic
      and pharmacodynamic parameters with clinically acceptable accuracy in individual
      patients.

PMID- 9579495
TI  - Mood during epidural patient-controlled analgesia with morphine or fentanyl.
AB  - BACKGROUND: Mood states during epidural opioids are not known. The authors
      studied the change in mood during the 48-h period of epidural morphine and
      epidural fentanyl in 47 patients after elective hip or knee joint arthroplasty.
      METHODS: An epidural catheter was inserted at the L2-L3 or L3-L4 interspace.
      Anesthesia was induced with thiopenthal and maintained with isoflurane and
      nitrous oxide. One hour before the conclusion of the operation, patients received
      an epidural bolus injection of 2 mg morphine (n = 23) or 100 microg fentanyl (n =
      24), followed by the same opiate (125 microg/ml morphine or 25 microg/ml
      fentanyl) epidurally delivered by a patient-controlled analgesia (PCA) pump in
      the postoperative period for 48 h. Mood was assessed using the bipolar form of
      the Profile of Mood States before operation and 24 h, 48 h, and 72 h after
      operation. RESULTS: There was no significant difference in pain intensity between
      the groups during epidural PCA. Mood states became more positive over time in the
      patients who received morphine (P < 0.01 at 48 h) and negative in those who were
      given fentanyl (P < 0.01 at 24 and 48 h, respectively) compared with those before
      the operation, and they were more positive in the morphine than in the fentanyl
      group at 24 h, 48 h (P < 0.05), and 72 h (P < 0.01). Patients in the morphine
      group were more composed, agreeable, elated, confident, energetic, and
      clearheaded than were those in the fentanyl group (P < 0.05). There was no
      correlation between mood scores and pain scores in either group. There was an
      inverse correlation at 48 h between mood scores and plasma fentanyl
      concentrations (r = -0.58, P < 0.05). CONCLUSION: Mood states are significantly
      more positive during epidural morphine PCA than they are during epidural fentanyl
      PCA.

PMID- 9579497
TI  - The self-inflating bulb to detect esophageal intubation during emergency airway
      management.
AB  - BACKGROUND: The negative-pressure test using a self-inflating bulb (SIB) during
      emergency intubation was studied to determine its reliability and predictive
      value in this setting. METHODS: The endotracheal tube (ETT) position was tested
      in 300 consecutive patients undergoing in-hospital emergency endotracheal
      intubation. Immediately after intubation and before ETT cuff inflation, the
      following protocol was strictly followed: (1) an SIB was compressed, connected to
      the ETT, and released. A 10-s period was allowed for the bulb to inflate. (2) The
      ETT cuff was inflated, and the ETT position was confirmed using colorimetric or
      infrared carbon dioxide detection, or both, combined with clinical evaluation.
      RESULTS: There were 19 esophageal intubations (6% incidence). The SIB correctly
      identified all patients with esophageal intubation (sensitivity, 100%) and
      correctly identified all but three ETTs placed in the trachea (specificity, 99%).
      The three tracheally placed tubes that were misidentified by the bulb syringe
      occurred during one case each of chronic obstructive pulmonary disease, copious
      secretions, and obesity; of note were three tracheally placed tubes that were
      misidentified by the carbon dioxide analyzers during cardiopulmonary
      resuscitation. CONCLUSIONS: The SIB proved to be a sensitive and specific test
      for esophageal intubation in the emergency setting when used according to the
      protocol described, and it is complementary to carbon dioxide detection. The
      predictive value of the bulb syringe appears to be improved when a prolonged
      period for reinflation is allowed. It holds particular promise because of its low
      cost and portability.

PMID- 9579496
TI  - Correlation of regional cerebral blood flow with ischemic electroencephalographic
      changes during sevoflurane-nitrous oxide anesthesia for carotid endarterectomy.
AB  - BACKGROUND: Carotid endarterectomy necessitates temporary unilateral carotid
      artery occlusion. Critical regional cerebral blood flow (rCBF) has been defined
      as the rCBF below which electroencephalographic (EEG) changes of ischemia occur.
      This study determined the rCBF50, the rCBF value at which 50% of patients will
      not demonstrate EEG evidence of cerebral ischemia with carotid cross-clamping.
      METHODS: Fifty-two patients undergoing elective carotid endarterectomy were
      administered 0.6-1.2% (0.3-0.6 minimum alveolar concentration) sevoflurane in 50%
      nitrous oxide (N2O). A 16-channel EEG was used for monitoring. The washout curves
      from intracarotid 133Xenon injections were used to calculate rCBF before and at
      the time of carotid occlusion by the half-time (t(1/2)) technique. The quality of
      the EEG with respect to ischemia detection was assessed by an experienced
      electroencephalographer. RESULTS: Ischemic EEG changes developed in 5 of 52
      patients within 3 min of carotid occlusion at rCBFs of 7, 8, 11, 11, and 13 ml x
      100 g(-1) x min(-1). Logistic regression analysis was used to calculate an rCBF50
      of 11.5 +/- 1.4 ml x 100 g(-1) x min(-1) for sevoflurane. The EEG signal
      demonstrated the necessary amplitude, frequency, and stability for the accurate
      detection of cerebral ischemia in all patients within the range of 0.6-1.2%
      sevoflurane in 50% N2O. CONCLUSIONS: The rCBF50 of 0.6-1.2% sevoflurane in 50%
      N2O, as determined using logistic regression analysis, is 11.5 +/- 1.4 ml 100 g(
      1) x min(-1). Further, in patients anesthetized in this manner, ischemic EEG
      changes due to carotid occlusion were accurately and rapidly detected.

PMID- 9579498
TI  - Sex-related differences in the influence of morphine on ventilatory control in
      humans.
AB  - BACKGROUND: Opiate agonists have different analgesic effects in male and female
      patients. The authors describe the influence of sex on the respiratory
      pharmacology of the mu-receptor agonist morphine. METHODS: The study was placebo
      controlled, double-blind, and randomized. Steady-state ventilatory responses to
      carbon dioxide and responses to a step into hypoxia (duration, 3 min; oxygen
      saturation, approximately 82%; end-tidal carbon dioxide tension, 45 mmHg) were
      obtained before and during intravenous morphine or placebo administration (bolus
      dose of 100 microg/kg, followed by a continuous infusion of 30 microg x kg(-1) x
      h(-1)) in 12 men and 12 women. RESULTS: In women, morphine reduced the slope of
      the ventilatory response to carbon dioxide from 1.8 +/- 0.9 to 1.3 +/- 0.7 l x
      min(-1) x mmHg(-1) (mean +/- SD; P < 0.05), whereas in men there was no
      significant effect (control = 2.0 +/- 0.4 vs. morphine = 1.8 +/- 0.4 l x min(-1)
      x mmHg(-1)). Morphine had no effect on the apneic threshold in women (control =
      33.8 +/- 3.8 vs. morphine = 35.3 +/- 5.3 mmHg), but caused an increase in men
      from 34.5 +/- 2.3 to 38.3 +/- 3 mmHg, P < 0.05). Morphine decreased hypoxic
      sensitivity in women from 1.0 +/- 0.5 l x min(-1) x %(-1) to 0.5 +/- 0.4 l x min(
      1) x %(-1) (P < 0.05) but did not cause a decrease in men (control = 1.0 +/- 0.5
      l x min(-1) x %(-1) vs. morphine = 0.9 +/- 0.5 l x min(-1) x %(-1)). Weight, lean
      body mass, body surface area, and calculated fat mass differed between the sexes,
      but their inclusion in the analysis as a covariate revealed no influence on the
      differences between men and women in morphine-induced changes. CONCLUSIONS: In
      both sexes, morphine affects ventilatory control. However, we observed
      quantitative and qualitative differences between men and women in the way
      morphine affected the ventilatory responses to carbon dioxide and oxygen.
      Possible mechanisms for the observed sex differences in the respiratory
      pharmacology of morphine are discussed.

PMID- 9579499
TI  - Changing from isoflurane to desflurane toward the end of anesthesia does not
      accelerate recovery in humans.
AB  - BACKGROUND: In an attempt to combine the advantage of the lower solubilities of
      new inhaled anesthetics with the lesser cost of older anesthetics, some
      clinicians substitute the former for the latter toward the end of anesthesia. The
      authors tried to determine whether substituting desflurane for isoflurane in the
      last 30 min of a 120-min anesthetic would accelerate recovery. METHODS: Five
      volunteers were anesthetized three times for 2 h using a fresh gas inflow of 2
      l/min: 1.25 minimum alveolar concentration (MAC) desflurane, 1.25 MAC isoflurane,
      and 1.25 MAC isoflurane for 90 min followed by 30 min of desflurane
      concentrations sufficient to achieve a total of 1.25 MAC equivalent
      ("crossover"). Recovery from anesthesia was assessed by the time to respond to
      commands, by orientation, and by tests of cognitive function. RESULTS: Compared
      with isoflurane, the crossover technique did not accelerate early or late
      recovery (P > 0.05). Recovery from isoflurane or the crossover anesthetic was
      significantly longer than after desflurane (P < 0.05). Times to response to
      commands for isoflurane, the crossover anesthetic, and desflurane were 23 +/- 5
      min (mean +/- SD), 21 +/- 5 min, and 11 +/- 1 min, respectively, and to
      orientation the times were 27 +/- 7 min, 25 +/- 5 min, and 13 +/- 2 min,
      respectively. Cognitive test performance returned to reference values 15-30 min
      sooner after desflurane than after isoflurane or the crossover anesthetic.
      Isoflurane cognitive test performance did not differ from that with the crossover
      anesthetic at any time. CONCLUSIONS: Substituting desflurane for isoflurane
      during the latter part of anesthesia does not improve recovery, in part because
      partial rebreathing through a semiclosed circuit limits elimination of isoflurane
      during the crossover period. Although higher fresh gas flow during the crossover
      period would speed isoflurane elimination, the amount of desflurane used and,
      therefore, the cost would increase.

PMID- 9579500
TI  - Effects of oral clonidine premedication on plasma glucose and lipid homeostasis
      associated with exogenous glucose infusion in children.
AB  - BACKGROUND: Oral clonidine may influence plasma glucose and lipid homeostasis by
      modulating endocrinologic responses to surgical stress. The effect of oral
      clonidine premedication on plasma glucose and lipid homeostasis associated with
      exogenous glucose infusion were investigated in children undergoing minor
      surgery. METHODS: Otherwise healthy children (n, 120; aged 3-13 yr) were assigned
      randomly to six groups according to the glucose concentration of the intravenous
      solution (0%, 2%, or 5%, at a rate of 6 ml kg(-1) x h(-1)) and the preoperative
      medications (4 microg/kg clonidine or placebo given 100 min before anesthesia)
      they were to receive. The plasma concentrations of glucose, nonesterified fatty
      acid, ketone bodies, epinephrine, norepinephrine, and cortisol were determined.
      RESULTS: Infusion of 5% glucose caused hyperglycemia (mean glucose concentration
      >200 mg/dl) in six children receiving placebo and two receiving clonidine.
      Although the mean plasma glucose concentration increased in three placebo groups,
      it was unchanged and the plasma concentrations of total ketone bodies and
      nonesterified fatty acid were increased in children receiving clonidine and
      glucose-free solution. The plasma epinephrine, norepinephrine, and cortisol
      levels in children receiving placebo increased in response to surgery. Clonidine
      attenuated the increase in catecholamines and cortisol. CONCLUSIONS: Oral
      clonidine premedication attenuated the hyperglycemic response, probably by
      inhibiting the surgical stress-induced release of catecholamines and cortisol.
      Infusion of 2% of glucose maintained plasma glucose concentrations within
      physiologic ranges in children receiving clonidine.

PMID- 9579501
TI  - Awakening propofol concentration with and without blood-effect site equilibration
      after short-term and long-term administration of propofol and fentanyl
      anesthesia.
AB  - BACKGROUND: The propofol awakening concentration can vary. However, the effect
      site awakening propofol concentration will be a fixed value. The purpose of this
      study was to determine the awakening propofol concentrations obtained from
      infusion Schede using abrupt discontinuation of propofol (half-maximal effective
      concentration [EC50]) or a descending decrease in concentration to allow blood
      effect site equilibration (EC50eq). METHODS: Patients undergoing short-term
      (group 1) and long-term (group 2) elective surgery were anesthetized with
      computer-assisted continuous infusion of propofol and fentanyl, with both groups
      receiving the same propofol (3 microg/ml) and fentanyl (1 ng/ml) concentrations
      20-30 min before the end of surgery until the end. Then both groups were further
      divided into two subgroups: subgroup A abrupt discontinuation, and subgroup B
      descending concentrations of propofol (15-min duration per concentration). In the
      A subgroups, the response to verbal command was evaluated every 30 s. In the B
      subgroups, the blood propofol concentrations just permitting and just preventing
      response to command were averaged individually. The EC50 and EC50eq values were
      determined by probit analysis. RESULTS: The EC50 of group 1A was 1 microg/ml,
      which was significantly less than the 1.6 microg/ml of group 2A (P < 0.05). The
      awakening time of group 1A was 5.2 +/- 1.8 min, which was significantly shorter
      than the 9.3 +/- 3.5 min of group 2A (means +/- SD). The EC50eq of both groups 1B
      and 2B was 2.2 microg/ml. CONCLUSIONS: The EC50eq was independent of propofol
      infusion length, compared with the EC50. Thus the potential for hysteresis during
      emergence from propofol anesthesia was confirmed.

PMID- 9579502
TI  - Open-lung biopsy in patients with acute respiratory distress syndrome.
AB  - BACKGROUND: It has been suggested that fibrosis present during the
      fibroproliferative phase of acute respiratory distress syndrome (ARDS) can be
      treated by corticosteroids. However, neither clinical nor microbiologic criteria
      permit differentiation of this fibroproliferative phase from a nosocomial
      pneumonia. The aim of this observational case series was to evaluate the safety
      and utility of open-lung biopsy (OLB) performed in patients receiving ventilatory
      support who had persistent ARDS despite negative bacterial cultures. METHODS:
      During a 4-yr period, 37 OLBs were performed in 36 of 197 patients receiving
      ventilatory support who had ARDS. The severity of ARDS was assessed by a lung
      injury score of 3.1 +/- 0.4 (mean +/- SD) and a median ratio of the partial
      pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of 118 mmHg.
      Histologic examination; bacterial, fungal, and acid-fast staining; and cultures
      of the tissue sample were performed. RESULTS: Fibrosis was present in only 41% of
      the lung specimens obtained by OLB. Only six patients received corticosteroids
      (17%). In 9 of the 15 patients with fibrosis, cytomegalovirus pneumonia precluded
      the use of corticosteroids. Histologic cytomegalovirus pneumonia was diagnosed in
      18 cases. Histologic bacterial or mycobacterial pneumonia was diagnosed in five
      cases. No significant change in arterial blood gases was noted as linked to the
      biopsy procedure except an increase of the PaO2/FiO2 ratio. One pneumothorax was
      diagnosed on a chest roentgenogram 12 h after OLB. Only one patient required
      blood transfusion during the 48-h period after OLB (for an hemothorax). Five
      patients had moderate air leaks from operative chest tubes for 2-10 days.
      CONCLUSIONS: Open lung biopsy appeared to be a useful and acceptably safe
      diagnostic technique in patients with ARDS. It permitted the diagnosis of
      unexpected cytomegalovirus pneumonia.

PMID- 9579503
TI  - The concordance of intraoperative left ventricular wall-motion abnormalities and
      electrocardiographic S-T segment changes: association with outcome after coronary
      revascularization. Multicenter Study of Perioperative Ischemia (McSPI) Research
      Group.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) and Holter electrocardiography
      (ECG) are used to detect intraoperative ischemia during coronary artery bypass
      graft surgery (CABG). Concordance of these modalities and sensitivity as
      indicators of adverse perioperative cardiac outcomes are poorly defined. The
      authors tried to determine whether routine use of Holter ECG and TEE in patients
      with CABGs has clinical value in identifying those patients in whom myocardial
      infarction (MI) is likely to develop. METHODS: A total of 351 patients with CABG
      and both ECG- and TEE-evaluable data were examined for the occurrence of ischemia
      and infarction. The TEE and five-lead Holter ECGs were performed continuously
      during cardiac surgery. The incidence of MI (creatine kinase-MB > or = 100 ng/ml)
      within 12 h of arrival in the intensive care [ICU] unit, new ECG Q wave on ICU
      admission or on the morning of postoperative day 1, or both, were recorded.
      RESULTS: Electrocardiographic or TEE evidence of intraoperative ischemia was
      present in 126 (36%) patients. The concordance between modalities was poor
      (positive concordance = 17%; Kappa statistic = 0.13). Myocardial infarction
      occurred in 62 (17%) patients, and 32 (52%) of them had previous intraoperative
      ischemia. Of these, 28 (88%) were identified by TEE, whereas 13 (41%) were
      identified by ECG. Prediction of MI was greater for TEE compared with ECG.
      CONCLUSIONS: Wall-motion abnormalities detected by TEE are more common than S-T
      segment changes detected by ECG, and concordance between the two modalities is
      low. One half of patients with MI had preceding ECG or TEE ischemia. Logistic
      regression revealed that TEE is twice as predictive as ECG in identifying
      patients who have MI.

PMID- 9579504
TI  - Suppression of spinal cord motoneuron excitability correlates with surgical
      immobility during isoflurane anesthesia.
AB  - BACKGROUND: Recent evidence suggests that the spinal cord is an important site of
      anesthetic action that produces surgical immobility. Inhalation anesthetics
      depress the Hoffmann's reflex (H reflex) and F wave, indicating spinal motoneuron
      suppression. The aim of this study was to assess the correlation between
      isoflurane-induced immobility and H- and F-wave suppression. METHODS: The
      baseline H reflex and F wave were measured before anesthesia in 15 adult
      patients. After induction, 1% end-tidal isoflurane was maintained for 20 min
      before the H and F waves were reelicited. Using an electric stimulus applied to
      the forearm and grading the response as movement or no movement, the authors
      increased or decreased the isoflurane concentration in 0.1% steps, depending on
      the movement responses. The H and F waves were recorded 20 min after each change
      of isoflurane concentration. The correlation between H- and F-wave suppression
      and surgical immobility was analyzed using a paired t test with Bonferroni
      correction. RESULTS: H-reflex amplitude (2.74 +/- 1.63 mV) and F-wave persistence
      (70.69 +/- 26.19%) at the highest isoflurane concentration that allowed movement
      response to a stimulus are different (P < 0.01) from these (1.97 +/- 1.46 mV;
      43.16 +/- 22.91%) at the lowest isoflurane concentration that suppressed
      response. At 0.8% isoflurane, the H-reflex amplitude was 3.69 +/- 1.83 mV with
      movement and 1.01 +/- 1.14 mV without movement (P < 0.01); F-wave amplitude was
      0.29 +/- 0.15 mV with movement and 0.11 +/- 0.06 mV without movement (P < 0.01);
      F-wave persistence was 80 +/- 22.36% with movement and 34.9 +/- 25.75% without
      movement (P < 0.01). CONCLUSIONS: The degree of H- and F-wave amplitude and F
      wave persistence suppression correlates with movement response, suggesting that
      isoflurane-suppressive action in the spinal cord plays a significant role in
      producing surgical immobility.

PMID- 9579505
TI  - The relation between the platelet-activated clotting test (HemoSTATUS) and blood
      loss after cardiopulmonary bypass.
AB  - BACKGROUND: Platelet dysfunction is one of several major causes of bleeding after
      cardiopulmonary bypass. A timely, simple, point-of-care determinant of platelet
      function recently became available for clinical use. Adding platelet-activating
      factor to conventional activated clotting time methods (platelet-activated
      clotting test [PACT]) produces rapid results (<15 min) and may yield a measure of
      platelet responsiveness and whole-blood procoagulant activity. METHODS: Blood
      samples were drawn from 100 patients after cardiac surgery on their arrival in
      the intensive care unit for PACT, platelet count, prothrombin time (PT), and
      activated partial thromboplastin time (aPTT). Cumulative blood loss at 4, 8, and
      12 h after arrival in the intensive care unit and perioperative transfusion
      requirements were quantitated. Coagulation tests and mediastinal blood loss were
      compared using the Spearman rank test and Pearson correlation. The sensitivity
      and specificity of the laboratory tests for predicting blood loss were analyzed
      using the receiver operating characteristic method. RESULTS: The PT was the only
      test that correlated with blood loss at 4, 8, and 12 h. The PACT did not
      correlate with blood loss at 4, 8, or 12 h, nor did the PACT correlate with the
      PT or the aPTT. The sensitivity and specificity of the PACT were less than those
      of the PT in predicting blood loss. Only the PT correlated with platelet and
      fresh frozen plasma transfusion. CONCLUSIONS: The PT correlated with blood loss
      and transfusion requirements and was superior to PACT, aPTT, and platelet count
      for predicting excessive blood loss after cardiopulmonary bypass.

PMID- 9579506
TI  - A randomized controlled trial comparing the cuffed oropharyngeal airway and the
      laryngeal mask airway in spontaneously breathing anesthetized adults.
AB  - BACKGROUND: The cuffed oropharyngeal airway (COPA), a modified Guedel airway, was
      compared with the laryngeal mask airway (LMA) during spontaneous breathing
      anesthesia. Specifically examined were ease of use, physiologic tolerance, and
      the frequency of problems. METHODS: Adult patients consented to random (2:1)
      assignment to either COPA (n = 302) or LMA (n = 151) for airway management during
      anesthesia with propofol, nitrous oxide, and oxygen. RESULTS: Ease of insertion
      was similar, but the first-time successful insertion rate was higher with the LMA
      (COPA, 81% compared with LMA, 89%; P = 0.05). More brief manipulations (head
      tilt, chin lift, jaw thrust) were reported in the COPA group (average total
      number of manipulations: COPA, 1.1 +/- 1.6 compared with LMA, 0.1 +/- 0.2; P <
      0.001). Continuous airway support was used more frequently in the COPA group
      (COPA, 30% compared with LMA, 0%; P < 0.0005). The incidences of aspiration,
      regurgitation, laryngospasm, wheezing, succinylcholine administration, oxygen
      saturation (SpO2) < 92%, failed use, and minor intraoperative problems were
      similar. When the airways were removed, blood was detected on the COPA less
      frequently than on the LMA (COPA, 5.8% compared with LMA, 15.3%; P = 0.001). The
      incidence of early and late sore throat was greater with the LMA (early: COPA,
      4.7% compared with LMA, 21.9% [P = 0.001]; late: COPA, 8.4% compared with LMA,
      16.1%; P = 0.01). The LMA did better than the COPA when anesthetists analyzed the
      technical aspects of the two devices. CONCLUSIONS: Although the COPA and LMA are
      equivalent devices in terms of physiologic alterations and overall clinical
      problems associated with their use, the LMA was associated with a higher first
      time insertion rate and fewer manipulations, suggesting that it is easier to use.
      The COPA was associated with less blood on the device and fewer sore throats,
      suggesting it may cause less pharyngeal trauma. Ultimately, both devices were
      similar in establishing a safe and effective airway for spontaneously breathing
      anesthetized adults.

PMID- 9579507
TI  - The pharmacokinetics and steady state pharmacodynamics of mivacurium in children.
AB  - BACKGROUND: The authors previously showed that children require larger infusion
      rates of mivacurium than adults to maintain target twitch depression. Here, they
      determined whether there are differences between children and adults in
      mivacurium's pharmacokinetic and pharmacodynamic properties. METHODS: Twenty
      seven patients aged 1-58 yr were anesthetized with nitrous oxide and isoflurane.
      Cholinesterase activity and adductor pollicis twitch tension in response to train
      of-four stimuli were measured. Mivacurium was infused, targeting 90% twitch
      depression. When twitch was stably depressed 85%-95% for 10 min with no change in
      infusion rate for 15 min, plasma was sampled to determine concentrations of
      mivacurium's stereoisomers. Clearance of the trans-trans (Cl(trans-trans)) and
      cis-trans (Cl(cis-trans)) isomers was determined as the mivacurium infusion rate
      (adjusted for isomer composition) divided by the concentration of that isomer.
      Using the Hill equation, assuming equipotency of the trans-trans and cis-trans
      isomers, and ignoring the contribution of the nonpotent cis-cis isomer, the
      authors estimated the steady state plasma concentration yielding 90% twitch
      depression, C90. The effect of age on cholinesterase activity, the infusion rate
      depressing twitch tension by 90% (IR90), C90, Cl(trans-trans), and Cl(cis-trans)
      was determined using linear regression. RESULTS: Cholinesterase activity, IR90,
      and C90 did not vary with age. Both Cl(trans-trans) (r2 = 0.19, P = 0.01) and
      Cl(cis-trans) (r2 = 0.19, P = 0.02) decreased with age. CONCLUSION: Clearance of
      mivacurium's potent isomers is larger in younger patients, consistent with the
      larger mivacurium infusion requirement in children than in adults reported
      previously.

PMID- 9579508
TI  - Regional cerebral plasma volume response to carbon dioxide using magnetic
      resonance imaging.
AB  - BACKGROUND: Noninvasive techniques used to determine the changes in cerebral
      blood volume in response to carbon dioxide are hampered by their limited spatial
      or temporal resolution or both. Using steady state contrast-enhanced magnetic
      resonance imaging, the authors determined regional changes in cerebral plasma
      volume (CPV) induced by hypercapnia in halothane-anesthetized rats. METHODS:
      Cerebral plasma volume was determined during normocapnia, hypercapnia and
      recovery in the dorsoparietal neocortex and striatum of each hemisphere, in
      cerebellum, and in extracerebral tissue of rats with either intact carotid
      arteries (group 1) or unilateral common carotid ligation (group 2). Another group
      was studied without injection of a contrast agent (group 3). RESULTS: Hypercapnia
      (partial pressure of carbon dioxide in arterial blood [PaCO2] approximately 65
      mmHg) resulted in a significant increase in CPV in the striatum (+42 +/- 8%),
      neocortex (+34 +/- 6%), and cerebellum (+49 +/- 12%) compared with normocapnic
      CPV values (group 1). Carotid ligation (group 2) led to a marked reduction of the
      CPV response to hypercapnia in the ipsilateral striatum (+23 +/- 14%) and
      neocortex (+27 +/- 17%) compared with the unclamped side (+34 +/- 15% and +38 +/-
      16%, respectively). No significant changes in CPV were found in extracerebral
      tissue. In both groups, the CPV changes were reversed by the carbon dioxide
      washout period. Negligible changes in contrast imaging were detected during
      hypercapnia without administration of the contrast agent (group 3). CONCLUSIONS:
      The contrast-enhanced magnetic resonance imaging technique is sensitive to detect
      noninvasively regional CPV changes induced by hypercapnia in rat brain. This
      could be of clinical interest for determining the cerebrovascular reactivity
      among different brain regions.

PMID- 9579509
TI  - The effect of the reduction of colloid oncotic pressure, with and without
      reduction of osmolality, on post-traumatic cerebral edema.
AB  - BACKGROUND: It has been asserted that reduction of colloid oncotic pressure (COP)
      can aggravate traumatic brain edema. To explore this issue, the authors measured
      the effect of COP reduction, with and without a simultaneous decrease in
      osmolality, on the development of brain edema after fluid percussion injury
      (FPI). METHODS: Isoflurane-anesthetized Wistar rats received a 2.7-atm right
      parasagittal FPI followed by isovolemic exchange with (1) normal saline (NS); (2)
      half-normal saline (0.5 NS); (3) whole blood (WB); or (4) hetastarch (Hespan,
      Dupont). Shed blood (16 ml) was replaced with donor erythrocytes suspended in the
      study fluid. The WB group received heparinized fresh donor WB. Central venous
      pressure was maintained with additional study fluid as required. The specific
      gravity (SG) of the cortex and subcortex near the impact site was determined 4.5
      h after FPI. The water content of the hemispheres was also determined using the
      wet-dry method. To define the status of the blood-brain barrier in the non-FPI
      hemisphere, two additional groups (FPI, non-FPI) were studied. Both groups
      received 30 mg/kg Evans' blue and NS at 4 ml/kg(-1)/h(-1). Four hours after FPI,
      the concentration of Evans' blue in the hemispheres was determined. RESULTS:
      After exchange, COP (mmHg +/- SD) decreased in the NS (9.6 +/- 2.1) and 0.5 NS
      (8.5 +/- 0.5) groups and was unchanged in the WB (16.7 +/- 3.3) and hetastarch
      (18.9 +/- 1.1) groups. Osmolality was unchanged in the WB group (295 +/- 5
      mOsm/kg), increased in the NS (304 +/- 3 mOsm/kg) and hetastarch (306 +/- 2
      mOsm/kg) groups, and was decreased in the 0.5 NS group (261 +/- 6 mOsm/kg). The
      Evans' blue data indicated that FPI resulted in blood-brain barrier damage in
      both hemispheres. In all four exchange groups, the SG of both cortical and
      subcortical tissue was less (indicating greater water content) in the impact
      hemisphere than in the nonimpact hemisphere. The SG was less in both hemispheres,
      although it was less in both hemispheres in the NS and 0.5 NS groups than in the
      WB and hetastarch groups. The lowest SG values were observed in the 0.5 NS group.
      The wet-dry water content determinations yielded a similar pattern of edema
      formation. CONCLUSIONS: These data, while confirming the important edematogenic
      effect of decreased osmolality, indicate that COP reduction per se can also
      aggravate brain edema after a mild to moderate mechanical head injury.

PMID- 9579510
TI  - Effects of neuromuscular blocking agents on excitatory transmission and gamma
      aminobutyric acidA-mediated inhibition in the rat hippocampal slice.
AB  - BACKGROUND: Although neuromuscular blocking agents do not cross the blood-brain
      barrier, they may penetrate the central nervous system under particular
      circumstances and eventually cause neurotoxic consequences. METHODS: The effects
      of neuromuscular blocking agents on excitatory and inhibitory transmission in
      area CA1 of rat hippocampal slices were investigated using extracellular and
      intracellular recording techniques. RESULTS: Application of atracurium in the
      perfusion medium resulted in a dose-dependent enhancement of excitatory synaptic
      responses averaging 48.7 +/- 4.3% at a concentration of 10 nM. This effect was
      correlated with an increase in the size of the presynaptic fiber volley.
      Laudanosine, but not pancuronium bromide or vecuronium bromide, produced similar
      changes. In addition, atracurium and laudanosine blocked inhibitory transmission
      and reduced intracellularly recorded gamma-aminobutyric acidA receptor-mediated
      potentials. These effects were observed only at concentrations >1 microM and were
      not reproduced by pancuronium bromide and vecuronium bromide. CONCLUSIONS:
      Atracurium and its metabolite, laudanosine, contrary to pancuronium bromide and
      vecuronium bromide, produce two distinct effects on hippocampal slices. They
      enhance excitatory transmission and neuronal excitability and they block
      inhibitory gamma-aminobutyric acidA-mediated synaptic responses.

PMID- 9579511
TI  - Induction of cyclooxygenase-2 in alveolar macrophages after acid aspiration:
      selective cyclooxygenase-2 blockade reduces interleukin-6 production.
AB  - BACKGROUND: Gastric acid aspiration can result in acute lung injury. In this
      study, the authors determined whether alveolar macrophages express cyclooxygenase
      2 as a source of inflammatory mediators after acid aspiration. METHODS: Seventy
      five microliters of hydrochloric acid solution, pH 1.15, was instilled into one
      lung in mice. After exposure, alveolar macrophages were harvested, and
      competitive polymerase chain reaction and enzyme-linked immunosorbent assay were
      performed to measure expression of cyclooxygenase-1 and -2, interleukin-1beta and
      -6, tumor necrosis factor-alpha, and inducible nitric oxide synthase (iNOS). The
      authors used immunocytochemistry to demonstrate expression of cyclooxygenase-2 in
      alveolar macrophages. Selective cyclooxygenase-2 blockade using N-2(
      cyclohexyloxy-4-nitrophenyl) methane-sulphonamide was done to characterize
      prostaglandin-cytokine interaction. RESULTS: Acid aspiration induced upregulation
      of cyclooxygenase-2 and interleukin-6. Tumor necrosis factor-alpha and iNOS were
      not upregulated. Interleukin-1beta was upregulated even with saline instillation
      but could not be detected in the supernatant of the cell culture. Alveolar
      macrophages harvested from mice instilled with acid showed a trend toward more
      production of prostaglandin E2 and produced higher concentrations of interleukin
      6 compared with alveolar macrophages from mice instilled with saline. Selective
      cyclooxygenase-2 blockade significantly decreased release of interleukin-6 from
      alveolar macrophages harvested from mice instilled with acid. CONCLUSIONS: Acid
      aspiration induces strong expression of cyclooxygenase-2 and production of
      interleukin-6 in alveolar macrophages. Selective cyclooxygenase-2 blockade
      reduced production of interleukin-6 by acid-stimulated alveolar macrophages.
      These studies suggest that the induction of cyclooxygenase-2 plays an important
      role in the systemic inflammatory response induced by acid aspiration.

PMID- 9579512
TI  - Pulmonary vasodilator response to adenosine triphosphate-sensitive potassium
      channel activation is attenuated during desflurane but preserved during
      sevoflurane anesthesia compared with the conscious state.
AB  - BACKGROUND: The objective of this study was to investigate the effects of
      sevoflurane and desflurane anesthesia on the pulmonary vasodilator response to
      the adenosine triphosphate-sensitive potassium channel agonist, lemakalim,
      compared with the response measured in the conscious state. In addition, the
      authors assessed the extent to which sympathetic alpha1-adrenoreceptor inhibition
      and cyclooxygenase pathway inhibition modulate the vasodilator response to
      lemakalim. METHODS: Twenty-four conditioned male mongrel dogs were chronically
      instrumented to measure the left pulmonary vascular pressure-flow relationship.
      After preconstriction with the thromboxane analogue, U46619, dose-response
      relationships to lemakalim were assessed on separate days in the conscious state
      and during sevoflurane (approximately 3.5% end-tidal) and desflurane
      (approximately 10.5% end-tidal) anesthesia (approximately 1.5 minimum alveolar
      concentration for each anesthetic agent). The effects of sympathetic alpha1
      adrenoreceptor inhibition (prazosin) and cyclooxygenase inhibition (indomethacin)
      on the pulmonary vasodilator response to lemakalim also were assessed in the
      conscious and desflurane-anesthetized states. RESULTS: Neither sevoflurane nor
      desflurane had a net effect on the baseline left pulmonary vascular pressure-flow
      relationship compared with the conscious state. The magnitude of the pulmonary
      vasodilator response to lemakalim was preserved during sevoflurane anesthesia but
      was attenuated (P < 0.05) during desflurane anesthesia compared with the
      conscious state. The attenuated lemakalim-induced vasodilator response during
      desflurane anesthesia was partially reversed (P < 0.05) by pretreatment with
      prazosin but not indomethacin. CONCLUSION: These results indicate that adenosine
      triphosphate-sensitive potassium channel-mediated pulmonary vasodilation is
      preserved during sevoflurane anesthesia but is attenuated during desflurane
      anesthesia. The attenuated response to adenosine triphosphate-sensitive potassium
      channel activation during desflurane anesthesia is partially mediated by reflex
      sympathetic alpha1-adrenoreceptor vasoconstriction.

PMID- 9579513
TI  - Effect of subarachnoid bupivacaine block on anesthetic requirements for
      thiopental in rats.
AB  - BACKGROUND: Subarachnoid bupivacaine blockade has been reported to reduce
      thiopental and midazolam hypnotic requirements in patients. The purpose of this
      study was to examine if local anesthetically induced lumbar intrathecal blockade
      would reduce thiopental requirements for blockade of motor responses to noxious
      and nonnoxious stimuli in rats. METHODS: After intrathecal and external jugular
      catheter placement, rats were assigned randomly to two groups in a crossover
      design study, with each rat to receive either 10 microl of 0.75% bupivacaine or
      10 microl of normal saline intrathecally. The doses of intravenously administered
      thiopental required to ablate the eyelid reflex, to block the withdrawal reflex
      of a front limb digit, and to block the corneal reflex were compared. In two
      separate groups of animals, hemodynamic parameters and concentrations of
      thiopental in the brain were compared between intrathecally administered
      bupivacaine and saline. RESULTS: The thiopental dose required to block the
      described responses was decreased with intrathecally administered bupivacaine
      versus intrathecally administered saline from (mean +/- SD) 40 +/- 5 to 24 +/- 4
      mg/kg (P < 0.001) for the eyelid reflex, from 51 +/- 6 to 29 +/- 6 mg/kg (P <
      0.005) for front limb withdrawal, and from 67 +/- 8 to 46 +/- 8 mg/kg (P < 0.01)
      for the corneal reflex. The concentration of thiopental in the brain at the time
      of corneal reflex blockade for the group given bupivacaine was significantly
      lower than in the group given saline (24.1 vs. 35.8 microg/g, P = 0.02).
      CONCLUSION: This study demonstrates that lumbar intrathecally administered local
      anesthetic blockade decreases anesthetic requirements for thiopental for a
      spectrum of end points tested. This effect is due neither to altered
      pharmacokinetics nor to a direct action of the local anesthetic on the brain;
      rather, it is most likely due to decreased afferent input.

PMID- 9579514
TI  - Inhibition of presynaptic sodium channels by halothane.
AB  - BACKGROUND: Recent electrophysiologic studies indicate that clinical
      concentrations of volatile general anesthetic agents inhibit central nervous
      system sodium (Na+) channels. In this study, the biochemical effects of halothane
      on Na+ channel function were determined using rat brain synaptosomes (pinched-off
      nerve terminals) to assess the role of presynaptic Na+ channels in anesthetic
      effects. METHODS: Synaptosomes from adult rat cerebral cortex were used to
      determine the effects of halothane on veratridine-evoked Na+ channel-dependent
      Na+ influx (using 22Na+), changes in intrasynaptosomal [Na+] (using ion-specific
      spectrofluorometry), and neurotoxin interactions with specific receptor sites of
      the Na+ channel (by radioligand binding). The potential physiologic and
      functional significance of these effects was determined by measuring the effects
      of halothane on veratridine-evoked Na+ channel-dependent glutamate release (using
      enzyme-coupled spectrofluorometry). RESULTS: Halothane inhibited veratridine
      evoked 22Na+ influx (IC50 = 1.1 mM) and changes in intrasynaptosomal [Na+]
      (concentration for 50% inhibition [IC50] = 0.97 mM), and it specifically
      antagonized [3H]batrachotoxinin-A 20-alpha-benzoate binding to receptor site two
      of the Na+ channel (IC50 = 0.53 mM). Scatchard and kinetic analysis revealed an
      allosteric competitive mechanism for inhibition of toxin binding. Halothane
      inhibited veratridine-evoked glutamate release from synaptosomes with comparable
      potency (IC50 = 0.67 mM). CONCLUSIONS: Halothane significantly inhibited Na+
      channel-mediated Na influx, increases in intrasynaptosomal [Na+] and glutamate
      release, and competed with neurotoxin binding to site two of the Na+ channel in
      synaptosomes at concentrations within its clinical range (minimum alveolar
      concentration, 1-2). These findings support a role for presynaptic Na+ channels
      as a molecular target for general anesthetic effects.

PMID- 9579515
TI  - Effect of differential delivery of isoflurane to head and torso on lumbar dorsal
      horn activity.
AB  - BACKGROUND: The spinal cord appears to be the site where anesthetic agents
      prevent movement in response to noxious stimuli. When isoflurane is
      differentially delivered to the head and torso (with low torso concentrations),
      cranial anesthetic requirements increase compared with systemic administration.
      The aim of the current study was to test the hypothesis that isoflurane action in
      the brain has descending influences on spinal cord dorsal horn neurons. A
      secondary aim was to determine the association, if any, of high cranial
      concentrations of isoflurane (>6%) with dorsal horn activity. METHODS: Ten goats
      were anesthetized with isoflurane and the carotid arteries and jugular veins
      isolated and cannulated for cerebral bypass. A laminectomy was performed for
      recording from single lumbar dorsal horn neurons with hind limb mechanical
      receptive fields (one cell per goat). A standard noxious mechanical stimulus was
      applied to the dew claw or hoof bulb during a control period with end-tidal
      isoflurane at 1.3% and during bypass with the following head/torso isoflurane
      concentrations: 1.3%/1.3%, 3.2%/1.3%, 9.4%/1.3%, 1.3%/0.2%, 3.0%/0.2% and
      8.8%/0.3%. RESULTS: When torso isoflurane concentration was 1.3%, increasing
      cranial isoflurane concentration to 3% or 9% had no significant effect on the
      activity of dorsal horn units. When torso isoflurane was 0.2-0.3%, spontaneous
      activity increased; however, at these torso concentrations, evoked responses were
      significantly decreased (-60%) only when cranial isoflurane concentration was
      increased to 9%. CONCLUSIONS: Isoflurane action in the brain had an inhibitory
      effect on dorsal horn activity with the combination of supraclinical cranial and
      low torso concentrations.

PMID- 9579516
TI  - Volatile anesthetic agents and vascular communication in the microcirculation of
      the hamster cheek pouch.
AB  - BACKGROUND: There is communication between tissue and the vascular network
      involved in regulating distribution of blood flow. Signals generated by the
      tissue are communicated upstream to create a coordinated network response in
      unison with other controllers of blood flow, such as myogenic and flow-dependent
      responses. METHODS: This vascular communication was modeled with the
      microapplication of methacholine (10(-4) M) or potassium chloride solution (KCl;
      100 mM) to arterioles (40-60 microm in diameter) of the cheek pouch of
      anesthetized hamsters and viewed with videomicroscopy. Local and conducted (500
      microm upstream) responses were measured. Halothane or isoflurane (1%, 2%, and
      3%) was equilibrated with the superfusion solution and applied to the entire
      tissue. Responses to KCl and methacholine were then repeated in the presence of
      an anesthetic agent. RESULTS: Halothane and isoflurane increased the resting
      diameter of the arterioles. They also decreased the methacholine-initiated
      dilations. To test for the effects of increased resting diameter on the
      dilations, 0%, 5% and 10% oxygen alone was applied to the pouch to alter the
      tone, and the methacholine responses were repeated. The dilations decreased with
      oxygen-induced increases in resting diameter, but the conducted dilation
      decreased to a lesser extent than was seen with the volatile anesthetic agents.
      Neither halothane nor isoflurane decreased constrictions caused by KCl.
      CONCLUSIONS: Decreased methacholine-initiated conducted dilations caused by
      halothane and isoflurane were not due to decreases in cell-cell communication
      because KCl conducted responses persisted. Therefore, cell-cell vascular
      communication appears intact in the presence of clinical concentrations of
      halothane and isoflurane.

PMID- 9579517
TI  - Pretreatment or resuscitation with a lipid infusion shifts the dose-response to
      bupivacaine-induced asystole in rats.
AB  - BACKGROUND: The authors sought to confirm a chance observation that intravenous
      lipid treatment increases the dose of bupivacaine required to produce asystole in
      rats. The authors also measured the partitioning of bupivacaine between the lipid
      and aqueous phases of a plasma-lipid emulsion mixture. METHODS: Anesthetized
      Sprague-Dawley rats were used in pretreatment (protocol 1) and resuscitation
      (protocol 2) experiments. In protocol 1, animals were pretreated with saline or
      10%, 20%, or 30% Intralipid (n = 6 for all groups), then received 0.75%
      bupivacaine hydrochloride at a rate of 10 ml x kg x min(-1) to asystole. In
      protocol 2, mortality was compared over a range of bolus doses of bupivacaine
      after resuscitation with either saline or 30% Intralipid (n = 6 for all groups).
      The lipid:aqueous partitioning of bupivacaine in a mixture of plasma and
      Intralipid was measured using radiolabeled bupivacaine. RESULTS: Median doses of
      bupivacaine (in milligrams per kilogram) producing asystole in protocol 1 were
      for 17.7 for saline, 27.6 for 10% Intralipid, 49.7 for 20% Intralipid, and 82.0
      for 30% Intralipid (P < 0.001 for differences between all groups). Differences in
      mean +/- SE concentrations of bupivacaine in plasma (in micrograms per
      milliliter) were significant (P < 0.05) for the difference between saline (93.3
      +/- 7.6) and 30% Intralipid (212 +/- 45). In protocol 2, lipid infusion increased
      the dose of bupivacaine required to cause death in 50% of animals by 48%, from
      12.5 to 18.5 mg/kg. The mean lipid:aqueous ratio of concentrations of bupivacaine
      in a plasma-Intralipid mixture was 11.9 +/- 1.77 (n = 3). CONCLUSIONS: Lipid
      infusion shifts the dose-response to bupivacaine-induced asystole in rats.
      Partitioning of bupivacaine into the newly created lipid phase may partially
      explain this effect. These results suggest a potential application for lipid
      infusion in treating cardiotoxicity resulting from bupivacaine.

PMID- 9579518
TI  - TOK1 is a volatile anesthetic stimulated K+ channel.
AB  - BACKGROUND: Volatile anesthetic agents can activate the S channel, a baseline
      potassium (K+) channel, of the marine mollusk Aplysia. To investigate whether
      cloned ion channels with electrophysiologic properties similar to the S channel
      (potassium selectivity, outward rectification, and activation independent of
      voltage) also are modulated by volatile anesthetic agents, the authors expressed
      the cloned yeast ion channel TOK1 (tandem pore domain, outwardly rectifying K+
      channel) in Xenopus oocytes and studied its sensitivity to volatile agents.
      METHODS: Standard two-electrode voltage and patch clamp recording methods were
      used to study TOK1 channels expressed in Xenopus oocytes. RESULTS: Studies with
      two-electrode voltage clamp at room temperature showed that halothane,
      isoflurane, and desflurane increased TOK1 outward currents by 48-65% in barium
      Frog Ringer's perfusate. The concentrations at which 50% potentiation occurred
      (EC50 values) were in the range of 768-814 microM (0.016-0.044 atm) and had a
      rank order of potency in atm in which halothane > isoflurane > desflurane. The
      potentiation of TOK1 by volatile anesthetic agents was rapid and reversible
      (onset and offset, 1-20 s). In contrast, the nonanesthetic 1,2
      dichlorohexafluorocyclobutane did not potentiate TOK1 currents in concentrations
      up to five times the MAC value predicted by the Meyer-Overton hypothesis based on
      oil/gas partition coefficients. Single TOK1 channel currents were recorded from
      excised outside-out patches. The single channel open probability increased as
      much as twofold in the presence of isoflurane and rapidly returned to the
      baseline values on washout. Volatile anesthetic agents did not alter the TOK1
      single channel current-voltage (I-V) relationship, however, suggesting that the
      site of action does not affect the permeation pathway of the channel. CONCLUSION:
      TOK1 is a potassium channel that is stimulated by volatile anesthetic agents. The
      concentrations over which potentiation occurred (EC50 values) were higher than
      those commonly used in clinical practice (approximately twice MAC).

PMID- 9579519
TI  - Effects of volatile anesthetic agents on in situ vascular smooth muscle
      transmembrane potential in resistance- and capacitance-regulating blood vessels.
AB  - INTRODUCTION: This study was designed to compare the inhibitory effect of inhaled
      volatile anesthetic agents on in situ sympathetic neural versus nonneural
      regulation of vascular smooth muscle transmembrane potentials as correlates of
      vascular smooth muscle tone in resistance- and capacitance-regulating blood
      vessels. METHODS: Vascular smooth muscle transmembrane potentials were measured
      in situ with glass microelectrodes in neurally intact, small (200-300 m OD)
      mesenteric arteries and veins of rats before, during, and after inhaled
      halothane, isoflurane, or sevoflurane (0.5 or 1.0 minimum alveolar concentration
      [MAC]). Such transmembrane potentials and their anesthetically induced changes
      were compared, respectively, with those measured in similar vessel preparations
      after local sympathetic neural denervation with 6-hydroxydopamine. RESULTS: In
      neurally intact vessels, transmembrane potentials (in millivolts, mean +/- SD)
      before inhalation of the anesthetic agent were -39 +/- 2.8 (artery) and -43 +/-
      4.6 (vein). At 1.0 MAC, halothane, isoflurane, and sevoflurane induced respective
      hyperpolarizations (in millivolts, mean +/- SD) of 9 +/- 3.1, 6 +/- 2.7, and 9 +/
      4.0 in arteries and 6 +/- 4.4, 2.8 +/- 3.0, and 8.7 +/- 5.6 in veins.
      Sympathetic denervation significantly attenuated these hyperpolarizations (except
      for venous response to isoflurane). At 0.5 MAC, transmembrane potential responses
      to all three volatile anesthetic agents were small and not consistently
      significant in either the intact or denervated vessels. CONCLUSIONS: In
      resistance-regulating arteries in situ, inhaled halothane, isoflurane, and
      sevoflurane (1.0 MAC) attenuate both sympathetic neural and nonneural regulation
      of vascular smooth muscle transmembrane potentials (and tone). In capacitance
      regulating veins in situ, sevoflurane (1.0 MAC) also attenuates both regulatory
      mechanisms, whereas halothane and isoflurane primarily attenuate nonneural
      mechanisms. At 0.5 MAC, none of these agents significantly affected either mode
      of regulation of vascular smooth muscle transmembrane potentials in arteries or
      veins.

PMID- 9579520
TI  - Effects of halothane on the sarcoplasmic reticulum Ca2+ stores and contractile
      proteins in rabbit pulmonary arteries.
AB  - BACKGROUND: The authors' purpose of this study was to elucidate the mechanisms of
      direct effects of halothane on the contractile proteins and Ca2+ release from the
      sarcoplasmic reticulum Ca2+ stores using isolated skinned strips (sarcolemma
      permealized with saponin) from rabbit pulmonary arteries. METHODS: The
      sarcoplasmic reticular Ca2+ stores were examined by immersing the skinned strips
      sequentially in solutions to load Ca2+ into and release Ca2+ from the
      sarcoplasmic reticulum using caffeine, inositol 1,4,5-trisphosphate, or
      halothane. The contractile proteins were assessed by activating the strips with
      Ca2+ followed by administration of halothane (with or without protein kinase C
      inhibitors). Tension, fura-2 fluorescence activated by Ca2+ release, and
      phosphorylation of myosin light chains were measured. RESULTS: Halothane (0.07
      3.00%) increased Ca2+, tension, and phosphorylation of myosin light chains in a
      dose-dependent manner. Halothane decreased accumulation of Ca2+ in the
      sarcoplasmic reticulum and enhanced the caffeine-induced tension transients. In
      strips pretreated with caffeine or inositol 1,4,5-trisphosphate, halothane
      induced tension transients were reduced but Ca2+ was not. In strips activated by
      1 microM Ca2+, halothane (0.5-3.0%) decreased 20-45% of the activated force at 15
      min. Halothane (3%) transiently increased the force (20%) associated with
      increases in Ca2+ and phosphorylation of myosin light chains. The increased force
      was abolished and the subsequent relaxation was enhanced by the protein kinase C
      inhibitor bisindolylmaleimide but not by indolocarbazole Go-6976. CONCLUSIONS: In
      skinned pulmonary arterial strips, halothane, at clinical concentrations,
      inhibits uptake of Ca2+ by and induces release of Ca2+ from intracellular stores
      possibly shared by caffeine and inositol 1,4,5-trisphosphate, which are regulated
      by phosphorylation of myosin light chains. The time-dependent inhibition of the
      contractile proteins by halothane may be mediated by Ca2+-independent protein
      kinase C.

PMID- 9579521
TI  - An inventive mind: the career of James O. Elam, M.D. (1918-1995).

PMID- 9579522
TI  - Unilateral pulmonary edema with interscalene block.

PMID- 9579523
TI  - Thrombocytopenia and subdural hemorrhage after desmopressin administration.

PMID- 9579524
TI  - A partial disconnection at the main stream CO2 transducer mimics "curare-cleft"
      capnograph.

PMID- 9579525
TI  - False-positive diagnosis of aortic dissection associated with femoral
      cardiopulmonary bypass.

PMID- 9579526
TI  - Vigilance--a main component of clinical quality.

PMID- 9579527
TI  - Use of remifentanil in patients breathing spontaneously during monitored
      anesthesia care and in the management of acute postoperative care.

PMID- 9579528
TI  - Predicting the severity of carbon monoxide poisoning at varying FIO2.

PMID- 9579529
TI  - An episode of malignant hyperthermia followed by a persisting muscle weakness.

PMID- 9579530
TI  - Pulse oximetry may not reliably assess peripheral perfusion.

PMID- 9579531
TI  - Perfusion monitoring during radical perineal prostatectomy: pulse oximetry is not
      reliable monitor of tissue perfusion.

PMID- 9579532
TI  - Rectal acetaminophen pharmacokinetics.

PMID- 9579533
TI  - Endoscopic saphenous vein harvesting and ETCO2 in cardiac surgery patients.

PMID- 9579534
TI  - Two-handed mask ventilation of the difficult airway by a single individual.

PMID- 9579535
TI  - Potent T cell stimulatory material with antigenic properties in stratum corneum
      of normal human skin.
AB  - T cell mediated autoimmunity may be important in inflammatory skin disease, but
      target autoantigens have not previously been described. In studies aimed at
      defining T cell epitopes, aqueous extracts of normal facial and plantar stratum
      corneum have consistently been found to induce potent proliferation of peripheral
      blood mononuclear cells from normal donors and patients with inflammatory skin
      disease, giving stimulation indices up to 80. Potent stimulation was seen with
      both autologous and allogeneic stratum corneum extracts. Because of the presence
      of inhibitory material, demonstration of the stimulatory activity was critically
      dependent on extract concentration, and was facilitated by short-term pulsing of
      cultures with extract. The proliferation of cells purified from peripheral blood
      mononuclear cells by immunomagnetic beads and immunophenotyping of cell lines
      generated from peripheral blood mononuclear cells, confirmed the T cell nature of
      the response to stratum corneum extracts. The activity was inhibited by HLA-DR
      monoclonal antibody, indicating the presence of antigen or superantigen. Tetanus
      toxoid reactive clones and a purified protein derivative reactive line failed to
      respond to the stratum corneum extracts, indicating that the active material is
      not a nonspecific T cell stimulant such as a cytokine or mitogen. This and the
      failure of recombinant interleukin-1alpha to stimulate peripheral blood
      mononuclear cells in concentrations up to 1000 U per ml, indicate that the
      activity is not due to interleukin-1. We propose the hypothesis that antigenic or
      superantigenic material is normally sequestered from the immune system in the
      epidermis, but induces T cell activation when released following wounding and in
      disease, and that this represents an important and previously unrecognized
      pathogenic mechanism.

PMID- 9579537
TI  - Cytokine induction in hairless mouse and rat skin after topical application of
      the immune response modifiers imiquimod and S-28463.
AB  - ALDARA (imiquimod cream 5%) recently became available for the treatment of
      genital and perianal warts; however, the topical mechanism of action of imiquimod
      is not fully understood. Imiquimod, and its analogs R-842, S-27609, and S-28463,
      are potent anti-viral and anti-tumor agents in animal models. Much of the
      biologic activity of these compounds can be attributed to the induction of
      cytokines, including interferon-alpha, tumor necrosis factor-alpha, interleukins
      1, -6, -8, and others. This study was performed to characterize the response of
      mice and rats to topical application of imiquimod and S-28463 and also to
      evaluate these agents in cultures of murine and human skin cells. Topical
      administration of imiquimod or S-28463 to the flanks of hairless mice and rats
      leads to increases in local concentrations of interferon and tumor necrosis
      factor in the skin. The concentrations of interferon and tumor necrosis factor
      were higher at the site of drug application than in skin from the contralateral
      flank or skin from untreated animals. Interferon-alpha mRNA levels were also
      elevated in the skin of mice after topical application of either imiquimod or S
      28463. In vitro, both imiquimod and S-28463 induced increases in interferon and
      tumor necrosis factor in cultures of cells isolated from hairless mouse skin.
      Imiquimod also increased interleukin-8 concentrations in human keratinocyte and
      fibroblast cultures, whereas S-28463 induced increases in tumor necrosis factor
      in fibroblast cultures. These results demonstrate that imiquimod and S-28463
      stimulate production of cytokines in the skin after topical application, which
      may play a major role in its activity in genital wart patients.

PMID- 9579536
TI  - Differential regulation of vitamin D responsive elements in normal and
      transformed keratinocytes.
AB  - Squamous cell carcinomas (SCC) derived from human epidermis fail to differentiate
      normally under the influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite
      the presence of the vitamin D receptor. Previous studies from our laboratory
      showed that phospholipase C-gamma1 (PLC-gamma1) was upregulated transcriptionally
      by 1,25(OH)2D3 in normal human keratinocytes, and a vitamin D responsive element
      (VDRE) in its promoter region has been identified. To examine the inducibility of
      human PLC-gamma1 transcription by 1,25(OH)2D3 and/or retinoic acid in SCC cell
      lines, we transiently transfected SCC4 and SCC12B2 cells with human PLC-gamma1
      promoter-luciferase constructs containing the VDRE and tested the response of
      these constructs to 1,25(OH)2D3 and/or all-trans retinoic acid. The induction of
      the human PLC-gamma1 VDRE by 1,25(OH)2D3 was synergistic with all-trans retinoic
      acid in normal human keratinocytes, but none of the constructs was induced by
      1,25(OH)2D3 and/or all-trans retinoic acid in SCC4 and SCC12B2 cells. In
      contrast, the construct containing the VDRE of the human 24-hydroxylase gene was
      induced several fold by 1,25(OH)2D3 in normal human keratinocytes and by both
      1,25(OH)2D3 and all-trans retinoic acid in SCC4 and SCC12B2 cells. DNA mobility
      shift assays showed that both the vitamin D receptor and the retinoic acid
      receptor in SCC4 and SCC12B2 cells bound the human PLC-gamma1 VDRE similarly to
      that seen in normal keratinocytes. The data indicate that the VDRE in the human
      PLC-gamma1 gene is not functional in SCC4 and SCC12B2 cells, unlike normal human
      keratinocytes, even though vitamin D receptors bind normally to it. Failure of
      transcriptional control of the PLC-gamma1 gene by 1,25(OH)2D3 suggests the lack
      of a cofactor(s) linking the VDRE to the transcriptional machinery.

PMID- 9579538
TI  - Immunologic abnormalities exhibited in IL-7 transgenic mice with dermatitis.
AB  - Interleukin (IL)-7 transgenic mice, which we established previously, developed
      severe dermatitis characterized by massive infiltration of gammadelta T cells in
      the dermal lesion. To fully understand the pathology of this intriguing skin
      disease, we examined several immunologic features of dermis infiltrating
      lymphocytes from the lesional skin of IL-7 transgenic mice. We observed a
      moderate response to mitogens, a poor response to alloantigens, and the absence
      of cytotoxic activities to several tumor cell lines and skin derived cells
      regardless of the presence of IL-2 or IL-7. On the other hand, dermis
      infiltrating lymphocytes could proliferate with exogenous IL-2 and IL-7.
      Moreover, reverse transcriptase polymerase chain reaction and fluorescence
      activated cell sorter analysis revealed that dermis infiltrating lymphocytes
      expressed various cytokines including IL-4 and IL-7, and several activation
      markers for T cells (CD44, CD69, IL-2R alpha), in addition to IL-7R alpha. In the
      sera of the affected mice, hyper epsilon-globulinemia was observed. These
      findings suggested that dermis infiltrating lymphocytes proliferated in an
      activated state in the skin lesion in an autocrine and/or paracrine manner and
      produced Th2 type cytokines that might evoke immunologic abnormalities. This
      study and previous findings suggest that IL-7 transgenic mouse with dermatitis
      offer the potential of serving as a useful tool for investigating the immunologic
      role of cutaneous gammadelta T cells, especially their participation in IgE
      production in vivo.

PMID- 9579539
TI  - Photodynamic therapy of B16F10 murine melanoma with lutetium texaphyrin.
AB  - Photodynamic therapy (PDT) of pigmented melanoma has generally been unsuccessful
      because of insufficient light penetration in such tissues. In this study, the
      responsiveness of the heavily pigmented B16F10 murine melanoma to lutetium
      texaphyrin (PCI-0123), a water-soluble sensitizer with strong absorbance in the
      near infrared (700-760 nm), was examined. These studies were carried out in both
      normal and ApoE deficient C57BL/6 mice. The latter strain exhibits a lipoprotein
      profile more like humans (low density lipoprotein > high density lipoprotein)
      than rodents (high density lipoprotein >> low density lipoprotein). Under optimal
      conditions of drug dose, light dose, and interval between drug administration and
      irradiation--the median survival time of C57BL/6 tumor bearing mice was
      approximately doubled (29 d) compared with tumor bearing control animals (13 d).
      The life-span of the ApoE knockout mice was greater (33 d) than the C57BL/6
      animals (23 d) when irradiation occurred 3 h after administration of a 10
      micromol per kg drug dose. The greater efficacy of PDT in the ApoE deficient mice
      was associated with more rapid clearance of drug from the blood, greater
      accumulation of sensitizer in tumor tissue, and substantially greater drug
      binding to the very low density lipoprotein/low density lipoprotein plasma
      fraction. Confocal laser scanning microscopy showed that the predominant
      subcellular site of photosensitizer binding was to melanosomes; costaining was
      performed with Mel-5. Melanosomes are susceptible to oxidative stress. Photo
      oxidation, mediated by PCI-0123 PDT, could potentially overload an already highly
      oxidized stressed state leading to cell death. The good tissue penetration depth
      achieved by PCI-0213 mediated PDT and the activation of melanosomes makes PDT of
      pigmented melanoma, for the first time, clinically relevant.

PMID- 9579540
TI  - Human papillomaviruses are commonly found in normal skin of immunocompetent
      hosts.
AB  - We have previously demonstrated, by the combined application of two degenerate
      polymerase chain reaction primer sets, the presence of human papillomavirus (HPV)
      DNA in 91% of cutaneous squamous cell cancers from renal allograft recipients,
      with multiple types being present in one-third of these tumors. Five HPV types-
      HPV 20, HPV 23, HPV 38, DL40, and DL267--accounted for 73% of positive results.
      These HPV types are all related to the epidermodysplasia verruciformis group, and
      HPV 38 was originally isolated from a melanoma. The aims of this study were to
      determine: (i) whether HPV DNA could readily be demonstrated in skin tumors, as
      well as in perilesional skin, of immunocompetent patients using two polymerase
      chain reaction primer sets; (ii) the prevalence of infections in normal skin; and
      (iii) the prevalence of HPV 38 or HPV 38 related viruses in melanoma. The HPV
      types detected in lesions from renal allograft recipient were present not only in
      the perilesional skin and tumors of immunocompetent patients, but also in 35% of
      normal skin biopsies. HPV DNA was present in 13% of the melanoma samples, but
      none harbored HPV 38 DNA. We identified four putatively new HPV types. Infections
      with different types of human papillomavirus are widespread and often occur in
      clinically normal skin. In vitro studies are required to determine the specific
      molecular mechanisms by which these HPV types may be involved in the etiology of
      nonmelanoma skin cancer.

PMID- 9579541
TI  - Depletion of human stratum corneum vitamin E: an early and sensitive in vivo
      marker of UV induced photo-oxidation.
AB  - As the outermost barrier of the body, the stratum corneum (SC) is frequently and
      directly exposed to a pro-oxidative environment, including ultraviolet solar
      radiation (UVR). Therefore, we hypothesized that the SC is susceptible to UVR
      induced depletion of vitamin E, the major lipophilic antioxidant. To test this,
      we investigated (i) the susceptibility of SC tocopherols to solar simulated UVR
      in hairless mice, (ii) the baseline levels and distribution patterns of
      tocopherols in human SC, and (iii) the impact of a suberythemogenic dose of solar
      simulated UVR on human SC tocopherols. SC tocopherol levels were measured by high
      performance liquid chromotography analysis of SC extracts from tape strippings.
      In murine SC, overall tocopherol concentrations were determined, whereas in human
      SC, 10 consecutive layers were analyzed for each individual. The results on SC
      tocopherols demonstrated (i) their concentration dependent depletion by solar
      simulated UVR in hairless mice; (ii) a gradient distribution within untreated
      human SC, with the lowest levels at the surface (alpha-tocopherol 6.5 +/- 1.4
      pmol per mg, and gamma-tocopherol 2.2 +/- 1.3 pmol per mg) and the highest levels
      in the deepest layers (alpha-tocopherol 76 +/- 12 pmol per mg, and gamma
      tocopherol 7.9 +/- 3.7 pmol per mg, n = 10; p < 0.0001); and (iii) the depletion
      of tocopherols in human SC by a single suberythemogenic dose of solar simulated
      UVR (alpha-tocopherol by 45%, and gamma-tocopherol by 35% as compared with
      controls; n = 6; both p < 0.01). These results demonstrate that the SC is a
      remarkably susceptible site for UVR induced depletion of vitamin E.

PMID- 9579542
TI  - Human dermal dendritic cells process and present soluble protein antigens.
AB  - Recently, a novel type of dendritic antigen-presenting cell has been identified
      in the dermis of normal human and mouse skin. These dermal dendritic cells (DDC)
      occur in higher numbers than epidermal Langerhans cells, represent a distinct
      differentiation pathway of dendritic cells, and are as potent as Langerhans cells
      in the activation of superantigen specific T cells. As yet, nothing is known
      about their capacity to take up, process, and present soluble protein antigens.
      We used the model of tetanus toxoid (TT) driven T cell proliferation to address
      these questions. To test for active internalization of TT protein, gold labeled
      TT was incubated with Langerhans cells and DDC and could be traced to
      multivesicular endo-lysosomal compartments. DDC internalize TT through a receptor
      mediated, clathrin-independent pathway, whereas Langerhans cells predominantly
      use macropinocytosis. To verify that DDC process TT by the exogenous pathway of
      antigen presentation, we pulsed DDC with TT protein or TT peptide after
      preincubation with chloroquine. Preincubation with chloroquine diminished the
      capacity of DDC to induce TT protein specific T cell proliferation (70-80%), but
      was not effective to suppress TT peptide induced T cell responses. DDC were as
      potent as Langerhans cells and 5-10 x more potent than plastic adherent monocytes
      in the presentation of TT to autologous resting T cells. Furthermore, as few as
      50 DDC (stimulator:responder ratio of 1:1000) were able to induce a significant
      TT specific T cell proliferation. Because a subpopulation of DDC expresses low
      levels of CD1a, a phenotypic marker of Langerhans cells, sorting of CD1a positive
      and negative DDC was performed. On a per cell basis, CD1a positive and negative
      DDC were equally potent at mediating TT specific T cell proliferation. Thus, DDC
      are able to internalize, process, and present soluble protein antigens such as TT
      and may therefore play an important role in the regulation of skin immune
      responses.

PMID- 9579543
TI  - Overexpression of p53 protein in cutaneous T cell lymphoma: relationship to large
      cell transformation and disease progression.
AB  - The molecular mechanisms by which advanced cases of cutaneous T cell lymphoma
      (CTCL) (mycosis fungoides/Sezary syndrome) undergo large cell transformation
      (LCT) and develop the morphologic appearance of a large cell lymphoma, are
      undefined. We used immunohistochemical analysis and polymerase chain
      reaction/single strand conformational polymorphism to examine whether p53
      mutations are associated with disease progression and LCT in CTCL. p53 protein
      immunohistochemistry was performed on 37 paraffin embedded biopsies from 27
      patients with CTCL; LCT was present in 15 biopsies. Overexpression of p53 protein
      was found in 11 of 37 CTCL biopsies including 10 of 15 biopsies (67%) with LCT in
      which p53 staining was predominantly seen in large transformed cells. In
      contrast, p53 immunostaining was found in only one of 22 CTCL biopsies without
      LCT (p < 0.0004). Serial biopsies revealed acquisition of p53 expression
      following LCT in two patients in whom initial diagnostic biopsies without LCT
      were p53 negative by immunostaining. All p53 protein positive biopsies were from
      advanced lesions (cutaneous tumors or extracutaneous sites); none of 12
      patch/plaque stage CTCL biopsies demonstrated p53 staining. Polymerase chain
      reaction/single strand conformational polymorphism and sequencing analysis of p53
      exons 4-8 was performed in 11 cases where frozen tissue was available. No
      mutations were detected in six cases positive for p53 protein expression. These
      results suggest overexpression of p53 protein in LCT and disease progression of
      CTCL by a mechanism other than p53 gene mutation, in most cases.

PMID- 9579544
TI  - Collagenase-1 complexes with alpha2-macroglobulin in the acute and chronic wound
      environments.
AB  - The purpose of this study was to examine the appearance and activation of
      collagenase-1 (MMP-1) in the wound environment. We found that MMP-1 accumulates
      in the fluid phase of the burn wound environment within 2 d of injury and reaches
      maximal levels by day 4. Two forms of the enzyme were evident; one that
      corresponded to proMMP-1 and another that corresponded to a group of high
      molecular mass (approximately 200 kDa and >200 kDa doublet) MMP-1 containing
      complexes. ProMMP-1 and MMP-1 containing complexes also occurred in wound fluid
      from venous stasis ulcers, but neither was detected in mastectomy fluid or in
      plasma. Levels of the proteinase inhibitor alpha2-macroglobulin in burn fluid and
      chronic ulcer wound fluid were almost as high as in plasma, and the high
      molecular mass MMP-1 containing complexes in burn fluid appeared to result from
      binding between alpha2-macroglobulin and activated MMP-1. These observations
      provide direct evidence that active MMP-1 in the fluid phase of the wound
      environment becomes complexed to alpha2-macroglobulin.

PMID- 9579545
TI  - Identification of a novel transcript produced by the gene responsible for the
      Hermansky-Pudlak syndrome in Puerto Rico.
AB  - Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive disorder that is
      characterized by oculocutaneous albinism, a predisposition to mild bleeding
      caused by storage-pool deficient platelets, and a ceroid storage disorder. A gene
      responsible for HPS in Puerto Rico maps to chromosome 10q2 and isolation of the
      gene has been reported. We have now identified a variant HPS cDNA that contains
      the same 5' sequence as the published HPS gene and a unique 3' sequence. Analysis
      of genomic DNA suggests that the two cDNA are derived from alternative
      transcripts of a single gene; two polyadenylated transcripts were found in normal
      human melanocytes, human bone marrow cells, human melanoma cells, lymphoblastoid
      cell lines, and megakaryocytic leukemia cells by reverse transcriptase polymerase
      chain reaction and northern analysis. The splicing exhibited by this gene is
      identical to the splicing found to produce two alternative transcripts of the
      Chediak-Higashi Syndrome gene, another pigment disorder exhibiting platelet
      storage pool deficiency. These studies show that the HPS gene on chromosome 10 is
      complex and may have more than one biologically active transcript.

PMID- 9579546
TI  - Lymphedematous skin and subcutis: in vivo high resolution magnetic resonance
      imaging evaluation.
AB  - Physico-chemical and morphologic parameters of skin layers and subcutaneous
      tissue in lymphedematous limb were studied in vivo using magnetic resonance
      imaging. High resolution images were obtained with a depth resolution of about 70
      microm, using a specific surface gradient coil specially designed for skin
      imaging and connected to a standard whole-body imager at 1.5 T. Twenty-one
      patients with unilateral lower extremity lymphedema (11 primary and 10 secondary)
      were examined. Skin thickness, relaxation times, and relative proton density were
      calculated in lymphedematous limbs and in contralateral extremities. In diseased
      limbs, the average skin thickness (2.17 mm) was significantly larger (p = 1.5 x
      10(-4)) than that of contralateral limb (1.14 mm). Major cutaneous alterations
      due to lymphedema took place in dermis. In lymphedematous dermis, the significant
      increase of relaxation time values could be due to a shift in the equilibrium of
      water inside this tissue in relation to the interactions between macromolecules
      and water molecules. In lymphedematous epidermis our results showed an increase
      in the number of free water protons. Information about water and fat distribution
      in lymphedema was also obtained using chemical shift weighted images. Our results
      demonstrated a water retention diffusely spread over the entire dermis, and an
      important fluid retention located in the interlobular spacing and beside the
      superficial fascia. Inside the subcutis, the mean thickness of the superficial
      fat lobules was increased more than that of the deep fat lobules. From all the
      various measurements we could not distinguish primary from secondary lymphedema.

PMID- 9579547
TI  - Excess cancer mortality in six Dutch pedigrees with the familial atypical
      multiple mole-melanoma syndrome from 1830 to 1994.
AB  - An increased incidence of systemic cancers has been described in some reports of
      familial atypical multiple mole-melanoma kindreds. If the gene defect underlying
      the familial atypical multiple mole-melanoma syndrome is not only important for
      the development of melanoma of the skin, the impact of the defect on life
      expectancy may be much higher than previously thought. We investigated all-cause
      mortality from 1830 to the present and causes of death from 1941 to 1994 in
      proven, obligate, and potential CDKN2 mutation carriers to obtain an estimate of
      the impact of a hereditary defect of the CDKN2 gene on mortality. From 1830 to
      1994 there were 65 deaths, although only 42 deaths were expected [standardized
      mortality ratio (SMR) 1.6, 95% confidence interval (CI) 1.2-2.0] and the SMR
      doubled with calendar time. Excess mortality was shown in most of the families,
      but was confined to ages 35-70 y (SMR 2.1, 95%CI 1.5-2.9). Excess mortality could
      be fully attributed to cancer mortality, especially to pancreatic carcinoma and
      melanoma of the skin. There appeared to be some heterogeneity among the families,
      especially due to the specific cancer pattern within a family. The impact of the
      defect of the CDKN2 gene is rising over calendar time, mainly because the
      mortality in the general population has been falling. Excess mortality was not
      only due to melanoma, but also to pancreatic carcinoma. Therefore, follow-up
      programs of affected family members should not be confined to a regular check of
      the atypical nevi.

PMID- 9579548
TI  - Normal human melanocytes that express a bFGF transgene still require exogenous
      bFGF for growth in vitro.
AB  - The expression of basic fibroblast growth factor (bFGF) has been implicated as an
      important factor in the development of malignant melanoma. The timing of this
      expression suggests that bFGF plays a role early in melanoma tumor progression.
      Benign nevi produce bFGF, and cells cultured from these lesions show a loss of
      dependence on exogenous bFGF for growth. We have examined the effects of
      constitutive bFGF expression on the in vitro growth requirements of normal human
      melanocytes. bFGF was overexpressed in normal human epidermal melanocytes through
      genomic insertion of a human bFGF cDNA in a retroviral vector. These melanocytes
      produced the 18 kDa bFGF isoform as well as the higher molecular weight isoforms.
      The bFGF was not released into the culture medium, but it was present in the cell
      nucleus. The bFGF produced by these cells was mitogenic for 3T3 fibroblasts and
      therefore possessed functional activity; however, melanocytes producing bFGF had
      the same appearance and growth patterns as those infected with control virus or
      uninfected melanocytes. Expression of bFGF did not confer independence from the
      exogenous mitogen, nor would these cells form colonies in a soft-agar medium.
      These results indicate that expression of bFGF alone is not enough to cause
      aberrant growth of normal human melanocytes.

PMID- 9579549
TI  - Genetically modified dermal keratinocytes express high levels of transforming
      growth factor-beta1.
AB  - In an attempt to genetically modify cultured keratinocytes with transforming
      growth factor-beta1 (TGF-beta1), which has been proven to be one of the most
      important cytokines involved in wound healing, two constructs were made. One,
      designated pG3Z:K14-TGF-beta1, is a plasmid in which the expression of TGF-beta1
      is driven by the keratin 14 promoter. The other, designated pLin-TGF-beta1, is a
      retroviral vector in which the retroviral 5' long-terminal repeat promoter drives
      expression. In both constructs, the deletion of a small fragment of the noncoding
      region of the TGF-beta1 gene was made to differentiate the transcript from that
      for endogenously expressed TGF-beta1. Different types of cells were transfected
      with the pG3Z:K14-TGF-beta1 construct using the calcium phosphate method. The
      pLin-TGF-beta1 construct was propagated in a retroviral packaging cell line and
      conditioned medium that contained high titers of the virus was used to transduce
      keratinocytes or other types of cells grown in standard culture. Northern
      analysis, used to evaluate the expression of TGF-beta1 mRNA in the pG3Z:K14-TGF
      beta1 transfected keratinocyte C1-177 cell line, showed a smaller TGF-beta1
      transcript compared with that endogenously expressed by dermal fibroblasts. The
      level of TGF-beta1 protein evaluated by enzyme-linked immunosorbent assay was
      significantly higher in medium conditioned by either the K14-TGF-beta1
      transfected or the pLin-TGF-beta1 transduced keratinocytes, compared with that
      obtained from control cells; however, the level of TGF-beta1 protein was
      unchanged in cultures of pG3Z:K14-TGF-beta1 transfected nonkeratinocyte cells
      such as fetal and adult fibroblasts. Using the mink lung epithelial cell growth
      inhibition assay, we found an increase in TGF-beta1 activity in conditioned
      medium from the pG3Z:K14-TGF-beta1 transfected cells. To evaluate possible
      paracrine effects of the keratinocyte derived TGF-beta1, a coculture system was
      established with pLin-TGF-beta1 transduced keratinocytes grown in the upper
      chamber and dermal fibroblasts in the lower chamber. The results showed that TGF
      beta1 released from keratinocytes diffused to the lower chamber where it
      stimulated collagen production by dermal fibroblasts. In summary, we demonstrate
      here that primary cultured keratinocytes can be genetically modified to express
      high levels of TGF-beta1 and suggest that this offers a potential approach for
      the therapy of dermal lesions such as nonhealing wounds.

PMID- 9579550
TI  - Supranuclear melanin caps reduce ultraviolet induced DNA photoproducts in human
      epidermis.
AB  - Melanin can form supranuclear caps in human epidermis, suggesting that
      intracellular melanin reduces ultraviolet transmission to underlying cell nuclei
      and inhibits the formation of ultraviolet induced DNA photoproducts. The purpose
      of this study was to determine the photoprotective effect of epidermal melanin.
      We irradiated normal human skin explants with ultraviolet B and determined the
      formation of cyclobutane pyrimidine dimers and (6-4)photoproducts in individual
      epidermal cells by indirect immunofluorescence and by laser cytometry using
      monoclonal antibodies specific for cyclobutane dimers or for (6-4)photoproducts.
      We found that epidermal cells with supranuclear melanin caps had significantly
      less DNA photoproducts (both types) than epidermal cells without supranuclear
      melanin caps. Moreover, the protection factor against both types of photolesions
      correlated with melanin concentration in epidermal cells. These results indicate
      that melanin reduces ultraviolet induced DNA photoproducts in human epidermis in
      a concentration dependent manner.

PMID- 9579551
TI  - Aloe barbadensis extracts reduce the production of interleukin-10 after exposure
      to ultraviolet radiation.
AB  - Cutaneous exposure to ultraviolet radiation suppresses the induction of T cell
      mediated responses such as contact and delayed type hypersensitivity (DTH) by
      altering the function of immune cells in the skin and causing the release of
      immunoregulatory cytokines. Extracts of crude Aloe barbadensis gel prevent this
      photosuppression. Because the regulation of contact hypersensitivity and DTH
      responses differ, we investigated whether protection was afforded by a single or
      multiple agents in Aloe and the mechanism by which this material prevents
      suppression of DTH immunity. The ability of Aloe gel to prevent suppression of
      contact hypersensitivity responses to hapten decayed rapidly after manufacture.
      In contrast, agents that protected against systemic suppression of DTH responses
      to Candida albicans were stable over time. Oligosaccharides prepared from
      purified Aloe polysaccharide prevented suppression of DTH responses in vivo and
      reduced the amount of IL-10 observed in ultraviolet irradiated murine epidermis.
      To assess the effect of Aloe extracts on keratinocytes, Pam 212 cells were
      exposed in vitro to ultraviolet radiation and treated for 1 h with Aloe
      oligosaccharides. Culture supernatants were collected 24 h later and injected
      into mice. Supernatants from ultraviolet irradiated keratinocytes suppressed the
      induction of DTH responses, whereas Aloe oligosaccharide treatment reduced IL-10
      and blocked the suppressive activity of the supernatants. These results indicate
      that Aloe contains multiple immunoprotective factors and that Aloe
      oligosaccharides may prevent ultraviolet induced suppression of DTH by reducing
      keratinocyte derived immunosuppressive cytokines.

PMID- 9579552
TI  - In situ hybridization analysis of the expression of human telomerase RNA in
      normal and pathologic conditions of the skin.
AB  - Human telomerase RNA (hTER) expression in skin was examined by in situ
      hybridization analysis. All newborn foreskins examined (n = 5) expressed hTER in
      epidermal basal cells at moderate levels. Telomerase RNA was not detectable in
      most adult specimens from sun protected areas (six of seven), whereas all samples
      obtained from sun exposed areas (n = 8) showed moderate hTER signals in epidermal
      basal cells. Telomerase RNA was also detected at moderate to strong levels in
      basal cells of psoriasis, contact dermatitis, and the proliferative cells of the
      anagen hair bulb. Basal cell carcinoma samples (14 of 15) had moderate to high
      hTER expression throughout the entire tumor, whereas squamous cell carcinomas
      (seven of eight) showed variable intensities of hTER expression but only in the
      cells at the periphery of tumor nests. All melanomas examined (n = 5) had
      moderate hTER expression in all tumor cells. The hTER signal intensities in skin
      tumors did not correlate with the age or sex of the donors, the clinical history
      of the lesions, or the histologic subtypes. To address whether hTER expression
      correlated with the proliferative state, sequential sections were stained with
      anti-Ki-67 antibody, a proliferation marker. In newborn foreskins, squamous cell
      carcinomas, and basal cell carcinomas, the distributions of hTER and Ki-67 were
      similar but not always identical. Telomerase RNA was more abundant than Ki-67 in
      the basal and suprabasal layer of newborn foreskins, suggesting that hTER
      expression is present both in actively cycling and in resting cells.

PMID- 9579553
TI  - Ultraviolet radiation induced suppression of Mantoux reactions in humans.
AB  - The effects of low dose ultraviolet (UV) radiation on delayed type
      hypersensitivity responses to tuberculin purified protein derivative were
      investigated in 17 healthy, Mantoux-positive volunteers. Suberythemal and
      erythemal doses of solar simulated UV from a fluorescent lamp source were
      delivered to the subjects' lower backs daily for five consecutive days. Mantoux
      testing with intradermally injected purified protein derivative was then
      performed at both the irradiated sites and an adjacent, unirradiated site, and
      the Mantoux induced erythema was quantitated 72 h later with a reflectance
      erythema meter. In comparison with the unirradiated Mantoux sites, Mantoux
      induced erythema was significantly reduced at the irradiated test sites. In six
      subjects, we compared the effects of chronic versus short term UV irradiation on
      the Mantoux reaction. These volunteers were irradiated on one side of their lower
      backs with the 5 d UV protocol, and on the other side of their backs for 4 or 5
      wk. In all but one subject, the short irradiation protocol induced greater
      suppression of Mantoux responses than prolonged UV exposure. We conclude that
      even suberythemal doses of UV significantly reduce delayed type hypersensitivity
      responses to purified protein derivative, and that an adaptive mechanism appears
      to counteract the immunosuppressive effects of chronic irradiation.

PMID- 9579554
TI  - Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in
      lethal junctional epidermolysis bullosa.
AB  - Herlitz junctional epidermolysis bullosa (OMIM#226700) is a lethal, autosomal
      recessive blistering disorder caused by mutations in one of the three genes
      LAMA3, LAMB3, or LAMC2, encoding the constitutive polypeptide subunits of laminin
      5. In this study, we describe a patient homozygous for a novel nonsense mutation
      Q936X in exon 19 of LAMB3, which has been mapped to chromosome 1q32. The patient
      was born with extensive blistering and demonstrated negative immunofluorescence
      staining for laminin 5, and transmission electron microscopy revealed tissue
      separation within lamina lucida of the dermal-epidermal junction, diagnostic of
      Herlitz junctional epidermolysis bullosa. The mother of the proband was found to
      be a heterozygous carrier for this mutation, whereas the father demonstrated the
      wild-type LAMB3 allele only. Nonpaternity was excluded by 13 microsatellite
      markers in six different chromosomes. Genotype analysis using 28 microsatellite
      markers spanning chromosome 1 revealed that the patient had maternal primary
      heterodisomy, as well as meroisodisomy within two regions of chromosome 1, one on
      1p and the other one on 1q, the latter region containing the maternal LAMB3
      mutation. These results suggest that Herlitz junctional epidermolysis bullosa in
      this patient developed as a result of reduction to homozygosity of the maternal
      LAMB3 mutation on chromosome 1q32.

PMID- 9579555
TI  - Homozygous R788W point mutation in the XPF gene of a patient with xeroderma
      pigmentosum and late-onset neurologic disease.
AB  - The second Caucasian xeroderma pigmentosum patient (XP42RO) belonging to
      complementation group F (XP-F) is described. Mild ocular photophobia was present
      from childhood, and acute skin reactions occurred upon exposure to sunlight.
      Basal and squamous cell carcinomas developed after his twenty-seventh year. In
      his late forties progressive neurologic symptoms emerged, which included
      intellectual decline, mild chorea and ataxia, and marked cerebral and cerebellar
      atrophy. Such neurologic abnormalities are very unusual in XP-F. Similar symptoms
      have been described in only one of 17 other XP-F individuals. His approximately 5
      fold reduced activity of nucleotide excision repair in cultured cells, combined
      with moderately affected cell survival and DNA replication after UV exposure, are
      typical of XP-F. The recent cloning of the XPF gene allowed a molecular genetic
      analysis of this unusual patient. XP42RO, representing the second case studied in
      this respect, turned out to be homozygous for a point mutation in the XPF gene,
      causing an R788-->W substitution in the encoded protein. Surprisingly, this
      mutation had also been found in one allele of the other unrelated Caucasian XP-F
      case. The amount of mutated XPF protein is strongly reduced in cells from XP42RO,
      presumably due to a conformational change. Biochemical, genetic, and clinical
      data all indicate the presence of considerable residual repair activity, strongly
      suggesting that the R788W mutation is leaky.

PMID- 9579556
TI  - A novel donor splice site mutation in the C1 inhibitor gene of a patient with
      type I hereditary angioneurotic edema.
AB  - We studied the molecular genetic basis of a C1 inhibitor deficiency in a patient
      with type I hereditary angioneurotic edema using both the polymerase chain
      reaction and nucleotide sequencing. A single nucleotide change (T-->A) at the GT
      5' donor splice recognition motif in the seventh intron of the C1 inhibitor gene
      was detected. A restriction site analysis of the C1 inhibitor gene in the
      patient's family indicated that this mutation is correlated with a decreased
      level of C1 inhibitor activity. A northern blot analysis demonstrated C1
      inhibitor mRNA to have a normal size, but its contents were reduced by about 50%
      compared with a normal subject. As the donor splice site is essential for an
      excising of the intron during mRNA processing, aberrant mRNA splicing may cause a
      rapid degradation of the transcript, thus resulting in the onset of hereditary
      angioneurotic edema.

PMID- 9579557
TI  - International Centennial Meeting on Pseudoxanthoma Elasticum: progress in PXE
      research.

PMID- 9579558
TI  - HPV sequences in blood of patients with condyloma acuminata.

PMID- 9579559
TI  - Superantigen production by Staphylococcus aureus in atopic dermatitis: no more
      than a coincidence?

PMID- 9579560
TI  - Narrowing of the Darier disease gene interval on chromosome 12q.

PMID- 9579561
TI  - HTLV-1 infection in a population-based cohort of older persons in Guinea-Bissau,
      West Africa: risk factors and impact on survival.
AB  - In 1989, a population-based cohort of persons aged > or = 50 years was
      established in an urban area of Guinea-Bissau, West Africa. Overall, 346 persons
      were interviewed in detail about risk behaviors and had capillary blood drawn.
      Among women, 12.4% were HTLV-1 seropositive, compared with 4.6% in men. No HTLV-2
      was found. Seropositivity varied considerably according to place of birth and
      ethnic group. In women, but not in men, HTLV-1 seropositivity was strongly
      associated with early sexual debut (10-14 yrs, 33.3%; 15-17 yrs, 26.0%; 18-20
      yrs, 6.5%; 21+ yrs, 0%; ptrend = 0.001), lifetime number of male partners (ptrend
      = 0.006), and the male partner's number of co-wives (ptrend = 0.006). There was
      also a 3.1-fold increased risk of being HTLV-1 seropositive if the woman was also
      HIV-2 seropositive. In a multivariate-risk-factor analysis, the strongest
      association with HTLV-1 was a history of having been bitten by a monkey (n = 11;
      combined OR adjusted = 10.1; 95% CI 2.3-44.4). Ornamental scarification was
      associated with a 3.3-fold increased risk. Ethnic affiliation also significantly
      influenced the risk of being HTLV-1 seropositive. Follow-up performed in January
      1996 revealed no difference in survival between HTLV-1-seropositive and 
      seronegative individuals over 6 years (rate ratio = 1.4, 95% CI 0.7-2.8). In
      conclusion, this population, which has very high HIV-2 seroprevalence, is also
      highly endemic for HTLV-1. Whereas sexual behaviors are clearly important for
      HTLV-1 spread in women, non-sexual risk factors were the only ones of potential
      importance in men. HTLV-1 had no impact on survival in this older population.

PMID- 9579562
TI  - High prevalence of codon 213Arg-->Stop mutations of the TP53 gene in human
      ovarian cancer in the southwestern part of The Netherlands.
AB  - As in many human malignancies, TP53 mutations are the most common genetic
      alterations in malignant human ovarian tumours. An approach often used in the
      determination of TP53 status is immunohistochemical staining of the protein. Non
      missense mutations, especially those of the null type, causing premature
      termination codons and resulting in truncated proteins, may often not be
      detectable by immunohistochemistry. Therefore, current estimates of TP53
      alterations in ovarian cancer may be inaccurate. By using polymerase chain
      reaction-single strand conformation polymorphism analysis and sequencing
      techniques, we have found a high prevalence of TP53 non-missense mutations in
      exons 5-8 in ovarian tumour specimens from patients from the southwestern part of
      The Netherlands. Twenty-nine of 64 tumours showed mutations, of which 10 were non
      missense mutations. The majority (9 of 10) of these non-missense mutations,
      including 7 nonsense mutations and 2 frameshift deletions, were null type
      mutations and could not be detected by immunohistochemical staining. Five of the
      7 nonsense mutations were mutations at codon 213 (Arg-->Stop). The nature of the
      high prevalence of this nonsense mutation in our series of ovarian carcinomas
      remains unknown. In addition to the 9 null type mutations, a splice junction
      mutation was encountered. In conclusion, we have observed a high prevalence (13%)
      of ovarian tumours with null type mutations in exons 5-8 that did not result in
      immunostaining. Our data suggest that, especially in ovarian cancer,
      immunological assessment of TP53 is not an adequate tool to study TP53
      alteration. A frequent nonsense mutation at codon 213 in 5 (8%) of 64 tumour
      specimens represents an important finding.

PMID- 9579564
TI  - Retention of the CDKN2A locus and low frequency of point mutations in primary and
      metastatic cutaneous malignant melanoma.
AB  - CDKN2A has been found mutated in melanoma families which show linkage to
      chromosome 9p21. In contrast, a low mutation rate has been found in melanomas,
      suggesting that CDKN2A might not be the first target for mutation in the
      development of this type of tumour. To elucidate the role of the CDKN2A gene and
      its alternative transcript p19ARF in the development of cutaneous malignant
      melanoma (CMM) we have analyzed 48 primary and metastasic CMM tumours for
      mutations and for loss of heterozygosity (LOH). Only one point mutation was
      detected (2%), while hemizygous deletions were identified in 20% of these
      tumours. Retention of the CDKN2A locus was found in 10 (47%) tumours with
      deletions at one or both sides of CDKN2A, suggesting that loss of this gene is
      not involved in CMM-tumour initiation and that another tumour-suppressor gene
      involved in melanoma is located at 9p21.

PMID- 9579563
TI  - Tumor-specific peptides in cutaneous T-cell lymphoma: association with class I
      major histocompatibility complex and possible derivation from the clonotypic T
      cell receptor.
AB  - We wished to identify and characterize tumor-associated class I peptides which
      could potentially serve as immunogens for an immunoprotective CD8 response in
      cutaneous T-cell lymphoma (CTCL). Candidate idiotypic peptides were identified
      from the third complementarity determining region (CDR3) of the clonotypic T-cell
      receptor (TCR) expressed on malignant T cells and native class I peptides were
      identified from CTCL cells. Idiotypic peptides were designed by sequencing of
      patients' CDR3 and identifying 9 amino acid peptides that could be accommodated
      in the peptide-binding motif of the class I alleles. Three candidate idiotypic
      peptides were synthesized and tested by measuring release of tumor necrosis
      factor-alpha (TNF-alpha) from autologous CD8 cells. Native peptides were acid
      eluted from class I molecules on CTCL lymphocytes, fractionated, tested in the
      TNF-alpha assay and sequenced. Two unique idiotypic peptides were specifically
      recognized by autologous CD8 cells from CTCL patients. In addition, a native
      peptide eluted from class I molecules of CTCL tumor cells was identified, in the
      protein data base, as a novel molecule with partial sequence homology to the
      conserved portion of the patient's TCR. This homology was used to construct an
      extended native peptide sequence that was immunogenic for CD8 cells from both
      CTCL patients. Our results demonstrate that peptides derived from the TCR can be
      used as tumor-specific immunogens that are recognized by CD8 cells. Moreover,
      novel class I peptides isolated from the tumor cell also serve as immunogens.
      These peptides might form the basis of an anti-tumor vaccine for immunotherapy of
      CTCL.

PMID- 9579565
TI  - p53 mutations in sweat gland carcinomas.
AB  - Sweat gland carcinomas are rare skin tumours and little is known about their
      etiology and molecular basis. In this study, we analyzed p53 mutations in 16
      sweat gland carcinomas with different histologic types, including 2
      spiradenocarcinomas, 1 composed adnexal carcinoma, 5 porocarcinomas, 2 eccrine
      hidradenocarcinomas, 2 syringocystadenocarcinomas, 1 sclerosing sweat gland
      carcinoma, 1 adenoid cystic carcinoma, 1 cylindrocarcinoma and 1 apocrine
      adenocarcinoma. Single-stranded conformation polymorphism (SSCP) analyses
      followed by direct DNA sequencing revealed that 5 carcinomas (31%) contained a
      p53 mutation, 4 of which were G:C-->A:T transition mutations and 1 of which was a
      deletion. Three G:C-->A:T mutations were located at dipyrimidine sequences on the
      antisense strand (2 spiradenocarcinomas, 1 eccrine hidradenocarcinoma),
      suggesting that UV light may play a role in the development of sweat gland
      carcinomas. In 2 spiradenocarcinomas, p53 mutations were present in the carcinoma
      but not in the adenoma portions, suggesting that p53 mutations may be associated
      with malignant progression in these rare adnexal tumours.

PMID- 9579566
TI  - Macronutrient intake and risk of colorectal cancer in Italy.
AB  - To provide further insight on the relationship between macronutrients and
      colorectal cancer, overall and by specific subsite(s), we carried out between
      1992 and 1996 in 6 Italian areas a case-control study on 1,953 individuals of
      both sexes with incident colorectal cancer (age range 19-74) and 4,154 controls
      (age range 19-74) in hospital with acute, non-neoplastic diseases. A validated
      food-frequency questionnaire was used, including questions on 78 foods or recipes
      and on individual fat-intake pattern. The risk of cancer of the colon and rectum
      increased with total energy intake (odds ratio in highest vs. lowest quintile
      1.43 and 1.50, respectively). The risk also rose significantly with an increase
      of starch intake, whereas it moderately decreased with an increase of protein
      intake. Monounsaturated fat intake appeared uninfluential, while saturated fat
      intake showed a modest direct association with rectal cancer. Polyunsaturated fat
      intake was inversely associated with colon cancer risk, particularly with the
      right colon.

PMID- 9579568
TI  - Demographic and familial characteristics of HTLV-1 infection among an isolated,
      highly endemic population of African origin in French Guiana.
AB  - To determine the epidemiological characteristics of human T cell
      leukemia/lymphoma virus type I (HTLV-I) infection in the endemic village of
      Maripasoula, French Guiana, 1,614 persons (83.2% of the population) aged 2 to 91
      years (mean age 21) were studied from November 1994 through April 1995. Plasma
      samples were screened by an HTLV-I ELISA and an IFA test (on MT2 cells), and
      positive samples were tested by an HTLV-I and -II type-specific Western blot.
      Overall seropositivity in the village was 6.7%, but HTLV-I infection was
      restricted to 3 of 6 ethnic groups, including the Noir-Marron (descendants of
      escaped African slaves, 8%), the Creoles (4.1%) and those of mixed Noir
      Marron/other ethnicity (3.6%). In the Noir-Marron population of 1,222 persons,
      including 606 men and 616 women and representing 76% of those tested, HTLV-I
      seroprevalence increased significantly with age in both sexes, reaching 40% in
      women older than 50 years. Univariate risk factors for HTLV-I seropositivity in
      women included older age, more pregnancies, more live births and a history of
      hospitalization. A cross-sectional analysis of sexual partners demonstrated an
      excess of discordant female HTLV-I+/male HTLV-I- couples, indicating preferential
      male-to-female sexual transmission. The demonstration of II HTLV-I-seropositive
      children aged less than 15 years, of whom 9 had a seropositive mother, suggested
      maternal-child HTLV-I transmission. Our results demonstrate a very high
      seroprevalence of HTLV-I in this South American population descended from African
      slaves, probably due to high rates of mother-to-child and sexual transmission
      within this rather isolated group.

PMID- 9579567
TI  - Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a
      large French case-control study. Federation Nationale des Centres de Lutte Contre
      le Cancer (FNCLCC).
AB  - Since tamoxifen is widely used in breast cancer treatment and has been proposed
      for the prevention of breast cancer, its endometrial iatrogenic effects must be
      carefully examined. We have investigated the association between endometrial
      cancer and tamoxifen use or other treatments in women treated for breast cancer
      in a case-control study. Cases of endometrial cancer diagnosed after breast
      cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast
      cancer and hospital and survival time with an intact uterus were included. Women
      who had received tamoxifen were significantly more likely to have endometrial
      cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001).
      Univariate and adjusted analyses showed that the risk increased with the length
      of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p =
      0.0001), irrespective of the daily dose. Women who had undergone pelvic
      radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001).
      After adjusting for confounding factors, the risk was higher for tamoxifen users
      (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic
      radiotherapy (p = 0.012). Women who had endometrial cancer and had received
      tamoxifen had more advanced disease and poorer prognosis than those with
      endometrial cancer who had not received this treatment. Our results suggest a
      causal role of tamoxifen in endometrial cancer, particularly when used as
      currently proposed for breast cancer prevention. Pelvic radiotherapy may be an
      additional iatrogenic factor for women with breast cancer. Endometrial cancers
      diagnosed in women treated with tamoxifen have poorer prognosis. Women who
      receive tamoxifen for breast cancer should be offered gynaecological surveillance
      during and after treatment. A long-term evaluation of the risk-benefit ratio of
      tamoxifen as a preventive treatment for breast cancer is clearly warranted.

PMID- 9579569
TI  - Duplication of two distinct regions on chromosome 5q in non-papillary renal-cell
      carcinomas.
AB  - RFLP studies have indicated a duplication of DNA sequences at the chromosome 5q22
      region and showed a breakpoint cluster between the apc and mcc genes in
      nonpapillary renal-cell carcinoma (RCC). We have now made a high-density
      fluorescent microsatellite assay to investigate the allelic status and determine
      the smallest duplication at this region in 62 sporadic non-papillary RCCs.
      Duplication at each informative locus was found in 27 cases. Partial duplications
      in 3 tumors delineated 2 distinct regions. One was found at loci D5S659, D5S1720
      and w2005 at chromosome band 5q22; this region partially overlaps with the
      smallest duplicated region found by previous RFLP analysis. Another small
      duplication was marked by loci D5S816 and D5S476 at chromosome band 5q31.1 and
      included the alpha-catenin gene (ctnna1).

PMID- 9579570
TI  - Trends in seroprevalence of human papillomavirus type 16 among pregnant women in
      Stockholm, Sweden, during 1969-1989.
AB  - To assess long-term trends in the prevalence of oncogenic human papillomavirus
      (HPV) infection, we performed a cross-sectional serosurvey of the seroprevalence
      of the major oncogenic HPV type, HPV16, among 3,512 pregnant women undergoing
      population-based serological screening at the first trimester of pregnancy in the
      same catchment area in Stockholm, Sweden, during 1969, 1983 or 1989. The overall
      HPV16 seroprevalence rates were 16% in 1969, 22% in 1983 and 21% in 1989.
      Seroprevalence was significantly increased, comparing both 1969 vs. 1983 (p =
      0.0005) and 1969 vs. 1989 (p = 0.008). By comparison, the previously reported
      herpes simplex 2 (HSV-2) seroprevalence in the same women increased from 17% in
      1969 to 32% in 1983 and 33% in 1989, whereas the seroprevalence rates of HSV-1
      were the same (69% in 1969, 63% in 1983 and 68% in 1989). Odds ratios for HPV 16
      positive women to also be HSV-2-positive were 1.8 in 1969 (p < 0.005), 1.1 in
      1983 (p = NS) and 1.0 in 1989. Our results suggest that both HSV-2 and HPV16
      became more generally spread in the Swedish population between 1969 and 1983 but
      that the spread has been stable during the 1980s.

PMID- 9579571
TI  - Anti-tumor effect of internal image bearing anti-idiotypic monoclonal antibody in
      relation to GM3 ganglioside.
AB  - Anti-idiotypic antibodies are a new type of useful tools for the possible
      treatment of cancer patients, since some act as antigen specific
      immunomodulators. Anti-idiotypic monoclonal antibody (anti-Id MAb) D704 (Ab2) was
      established which bore the internal image of the determinant defined by MAb M2590
      (Ab1) against a sialic acid residue on GM3 ganglioside. In an in vivo syngeneic
      tumor system, anti-Id MAb D704 was more effective in preventing tumor
      progression, as compared with anti-GM3 MAb or no treatment. Significant
      suppression of tumor growth and prolongation of survival by administration of
      anti-Id MAb D704 in an animal group inoculated with 1 x 10(4)/mouse melanoma
      cells were seen, but not in a group inoculated with 5 x 10(4) cells/mouse. In an
      active specific immunotherapy protocol utilizing Ab2, the activity of anti-anti
      Id antibodies (Ab3) specific for GM3 (antigen) which has a weak immunogenicity
      only, was maintained for more than 3 months. Ab2 generated cellular anti-tumor
      immune responses, including delayed type hypersensitivity (DTH) reaction.
      Immunohistological analysis indicated a marked infiltration of CD4 and CD8
      positive cells into the DTH sites. Our results suggest that internal image
      bearing anti-Id MAbs have a therapeutic potential against tumors if the number of
      melanoma cells is relatively low or if hosts are at an early stage of melanoma
      progression.

PMID- 9579572
TI  - DNA damage and prediction of radiation response in lymphocytes and epidermal skin
      human cells.
AB  - The success of radiotherapy in eradicating tumours depends on the total radiation
      dose, but what limits this dose is the tolerance of the normal tissues within the
      treatment volume. Studies involving fibroblast survival have demonstrated the
      theoretical feasibility of a predictive assay of radiation sensitivity, but such
      an assay is still far from clinical application. Using pulsed-field gel
      electrophoresis (PFGE), we have quantified the initial "apparent" number of DNA
      double-strand breaks (dsb) induced by the radiation as an alternative measure of
      sensitivity in 2 different normal cell types from the same patients, epidermal
      skin cells and lymphocytes. We found significant inter-individual variation in
      the measured dsb (1-5 dsb/Gy/DNA unit). We also found a linear correlation
      between molecular damage in lymphocytes and skin samples from the same patient
      (slope = 0.83; r = 0.694; p = 0.0001). These results suggest that the initial
      number of dsb could be used as an indicator of the in vivo response to radiation.

PMID- 9579573
TI  - Secretion of urokinase and metalloproteinase-9 induced by staurosporine is
      dependent on a tyrosine kinase pathway in mammary tumor cells.
AB  - Urokinase-type plasminogen activator (uPA) is a key serine protease involved in
      invasion and metastasis. We had shown that overproduction of uPA in tumor cells
      is controlled by a phospholipase D-protein kinase C-dependent pathway. Now we
      studied whether other signaling pathways participate in the regulation of
      constitutive uPA and metalloproteinase (MMP) overproduction in tumor cells.
      Staurosporine, a protein kinase inhibitor, stimulated uPA and MMP-9 secretion as
      measured by radial caseinolysis, zymography and Western blotting. Genistein, a
      specific tyrosine kinase inhibitor, reduced the constitutive and staurosporine
      induced uPA and MMP-9 secretion. Interestingly, the phosphatase inhibitor
      vanadate stimulated uPA secretion. Verapamil, a calcium channel blocker,
      inhibited both endogenous and PMA-stimulated secretion of uPA but was unable to
      inhibit staurosporine-induced secretion. The alcohol n-butanol, a phospholipase D
      and protein kinase C inhibitor, besides inhibiting constitutive uPA secretion,
      blocked staurosporine-induced secretion. Our results suggest that constitutive
      and staurosporine-induced uPA and MMP-9 secretion by LM3 murine mammary tumor
      cells is controlled by an endogenous tyrosine kinase pathway and probably
      involves protein phosphatases. In addition, the staurosporine-induced signal
      regulating urokinase secretion is independent of extracellular calcium but
      dependent on phospholipase D.

PMID- 9579574
TI  - Functional retinoid and thyroid hormone receptors in human thyroid-carcinoma cell
      lines and tissues.
AB  - Thyroid carcinomas no longer accessible to radio-iodide or TSH-suppressive T4
      therapy, due to loss of thyroid-specific functions, might be sufficiently re
      differentiated by retinoic acid (RA) to be treated by conventional methods again.
      To help evaluate the feasibility of RA re-differentiation therapy in thyroid
      carcinomas, we examined the functionality of RA receptors (RARs/RXRs), central RA
      signal mediators, in human thyroid-carcinoma cell lines as model systems. [3H]-RA
      binding assays with nuclear extracts from follicular thyroid-carcinoma cell lines
      FTC-133 and -238 revealed high-affinity binding sites for RA. Electrophoretic
      mobility shift and super-shift assays using a DR2 ("direct repeat" 2) RA response
      element demonstrated DNA-binding of RARalpha, RARgamma, RXRalpha and RXRbeta in
      nuclear extracts of FTC-133 and anaplastic HTh74 cells. Use of a DR5 RA response
      element revealed no difference in DNA binding. In supershift assays with a DR4 T3
      response element, we found DNA-binding by TRalpha1, TRalpha2, and TRbeta.
      Northern-blot analysis showed low expression of RXRbeta mRNA in FTC-133 and of
      TRalpha1 mRNA in FTC-133 and FTC-238 cells. Using RT-PCR, we detected mRNA for
      RARalpha, RARbeta, RARgamma, RXRalpha, and RXRbeta in the 4 cell lines and in
      human thyroid-carcinoma samples. RARbeta mRNA was reduced in FTC-238 cells and
      RXRbeta mRNA was decreased in anaplastic C643 cells and 9 of 12 tumor samples.
      Differential RA regulation of RA-receptor-mRNA expression was observed in the
      various cell lines. Thus, RA and T3 nuclear receptors are present in thyroid
      carcinoma cell lines or tissues, albeit with cell-line and tumor-dependent
      variations; in the cell lines, they were shown to be functional with respect to
      DNA and/or ligand binding.

PMID- 9579575
TI  - Increased invasiveness of MUC1 and cDNA-transfected human gastric cancer MKN74
      cells.
AB  - MUC1 mucin is an anti-adhesion molecule expressed in a wide variety of tumors. To
      examine whether MUC1 mucin is involved in tumor invasion, we have prepared MUC1
      transfectants using the human gastric cancer cell line MKN74 and performed an in
      vivo tumor assay by transplanting these into nude mice. Tumor weight at 71 days
      after s.c. injection of transfectants was measured, showing that the in vivo
      growth of MUC1 transfectants was increased compared to that of mock
      transfectants. Furthermore, MUC1-transfectant tumors invaded into the muscle
      layer, whereas mock-transfectant tumors did not. In vitro invasion, adhesion to
      extracellular matrix components and phagokinetic track motility were then
      evaluated to analyze the mechanisms for the in vivo invasiveness of the
      transfectants. MUC1 transfectants exhibited an increased in vitro invasiveness,
      decreased binding to laminin, fibronectin, type I collogen and type IV collagen
      and increased motility. These effects of MUC1 mucin over-expression in MKN74
      cells were abolished by the treatment of transfectants with an inhibitor of O
      glycan biosynthesis, benzyl-alpha-GalNAc. Our data suggest that MUC1 mucin could
      be related to the increased invasive ability of MKN74 cells, whereas O-glycan
      might play an essential role.

PMID- 9579576
TI  - Resistance to high concentrations of methotrexate and 5-fluorouracil of
      differentiated HT-29 colon-cancer cells is restricted to cells of enterocytic
      phenotype.
AB  - Adaptation of HT-29 cells to increasing concentrations of methotrexate (MTX)
      results in the selection of differentiated populations which show sequential dose
      dependent changes of their differentiated phenotype with, at the highest
      concentrations (0.1 and 1 mM), a shift of differentiation from a mucus-secreting
      to an enterocytic phenotype coinciding with an amplification of the DHFR gene. We
      show here that DHFR gene amplification itself does not play a role in the shift
      of differentiation. An alternative explanation is the presence, within the mucus
      secreting population, of an undetectable minor population of cells committed to
      enterocytic differentiation and able to develop resistance to higher
      concentrations of MTX. This was confirmed by cloning the population of cells
      resistant to 10 microM MTX. Out of 19 isolated clones, 17 were found to be mucus
      secreting and 2 enterocytic. We tested 9 of these clones for their ability to
      develop resistance to 0.1 mM MTX: only 1 of enterocytic phenotype, was found to
      develop resistance to this higher concentration and to amplify the DHFR gene. The
      ability of enterocytic cells to develop resistance to elevated MTX concentration
      through amplification of the DHFR gene was demonstrated in another enterocytic HT
      29 population selected by glucose deprivation. Enterocytic cells resistant to 10
      microM MTX were also found, unlike mucus-secreting cells, to be readily adaptable
      to 5-fluorouracil, this occurring without amplification of the thymidylate
      synthase gene. Together these results highlight a previously uncharacterized
      relationship between commitment to enterocytic differentiation of colon-cancer
      cells and their ability to develop resistance to MTX and 5-fluorouracil.

PMID- 9579577
TI  - Peritoneal fluid from ovarian cancer patients stimulates MUC1 epithelial mucin
      expression in ovarian cancer cell lines.
AB  - The MUC1 epithelial mucin is a transmembrane glycoprotein that is frequently but
      variably over-expressed by adenocarcinomas. It is used as a diagnostic serum
      tumour marker and is a candidate target for tumour immunotherapy. Peritoneal
      fluid (PF) samples from ovarian cancer patients were investigated for their
      ability to modulate MUC1 expression in 6 ovarian cancer cell lines which showed a
      range from very low to high endogenous MUC1 expression. Cell lines were cultured
      in 20% PF for 4 days, fixed in situ and MUC1 assayed by ELISA. MUC1 expression
      was stimulated by some PF samples in 5 of 6 lines tested. MUC1 expression in the
      PE04 cell line (very low endogenous expression) was increased by 35 of 36 PFs
      tested (p < 0.05); stimulation varied between PFs but was greater than with 100
      IU/mL hu-r-gamma-interferon. Western blotting confirmed the stimulation of MUC1
      in PE04 cells and FACS showed an increase in the proportion of cells expressing
      MUC1. The active factor was partially purified by gel filtration and was shown to
      stimulate PE04 cells in a dose-dependent manner. Concentrations of IL1beta, IL4,
      IL6, IL8, IL10, TNF-alpha, TGF-beta and GM-CSF were often very high in PF and
      varied substantially between different PF samples but did not correlate with the
      degree of MUC1 stimulatory activity.

PMID- 9579578
TI  - Specific latent membrane protein 1 gene sequences in type 1 and type 2 Epstein
      Barr virus from nasopharyngeal carcinoma in Hong Kong.
AB  - We reported previously that a characteristic Epstein-Barr virus latent membrane
      protein 1 (EBV-LMP1) gene was associated with nasopharyngeal carcinoma (NPC) in
      Hong Kong. It showed a 30 bp deletion at the carboxyl terminus with specific
      amino acid substitution Asp at codon 335 with reference to Gly in B95-8 LMP1.
      This deletion variant Asp335 was present in over 90% of NPC biopsy specimens. The
      present study attempted to determine the whole encoding sequence of the LMP1 gene
      in different EBV isolates from NPC, and its relation with EBV types. We found
      that 92% (34/37) of primary NPC tumours harboured EBV-1 and possessed the LMP1
      deletion variant, of which 86% were Asp335 and 6% were Gly335. EBV-2 was present
      in 8% (3/37) of tumours and all contained the retention variant of the LMP1 gene.
      Sequencing of the whole encoding region of the LMP1 gene revealed that the
      deletion variant Asp335 and deletion variant Gly335 carried similar sequences.
      They showed 43 common nucleotide substitutions in 41 codons with reference to B95
      8. The retention variant showed 52 base changes in 46 codons compared with B95-8.
      The amino acid alterations in both the deletion and retention variants were
      mostly clustered at the transmembrane domain of the protein. Furthermore, half of
      the substitutions were common to both variants, suggesting a common evolutionary
      selection pressure. Nonetheless, the 2 LMP1 variants showed differences in
      nucleotide alterations and were associated with different EBV types, suggesting
      the presence of 2 distinct EBV strains in Hong Kong NPC.

PMID- 9579579
TI  - Genetic instability and mutation of the TGF-beta-receptor-II gene in ampullary
      carcinomas.
AB  - Ampullary carcinomas are relatively rare cancers of which very little is known in
      terms of carcinogenetic mechanisms at the molecular level. Genetic instability
      caused by mutations of mismatch-repair genes has been demonstrated to be
      responsible for hereditary non-polyposis colorectal cancers and a sub-set of
      sporadic colorectal cancers. In some of those tumors showing genetic instability,
      the transforming-growth-factor-beta(TGF-beta)-receptor-II gene has been found to
      be mutated in repetitive sequences and considered to be a target of replication
      error. We studied the role of genetic instability and associated TGF-beta
      receptor-II-gene mutations in a series of 18 sporadic cases by analyzing 5
      microsatellite loci (D2S123, D3S1029, D5S409, TP53 and BAT26) and by sequencing a
      poly-A repeat (nucleotides 709-718) in the TGF-beta-receptor-II gene.
      Microsatellite instability was observed in 4 (22.2%) and gene mutations in 14
      (77.8%) cases. These data indicate that the TGF-beta-receptor-II gene might be a
      preferential target of genetic instability whose alteration might be specifically
      advantageous and constitute a common step in the development of ampullary
      carcinomas.

PMID- 9579580
TI  - Non-random allelic losses at 3p, 11p and 13q during HPV-mediated immortalization
      and concomitant loss of terminal differentiation of human keratinocytes.
AB  - To obtain a comprehensive overview of chromosomal alterations that may underlie
      human papillomavirus (HPV)-mediated immortalization, 4 foreskin keratinocyte cell
      lines generated by transfection with either HPV 16 (cell lines FK16A and FK16B)
      or HPV 18 (FK18A and FK18B) were subjected to chromosomal analysis using
      comparative genomic hybridization (CGH). Three cell lines were analyzed both in
      the mortal state during their extended lifespan and in the subsequent immortal
      state. From cell line FK18A, only immortal cells were tested. Chromosomal
      imbalances increased in number through the process of immortalization. Subsequent
      loss of heterozygosity (LOH) analysis, using a panel of 21 microsatellite markers
      selected on the basis of CGH losses, revealed no clonal LOHs in cells at the
      mortal stage. However, in the immortal descendants 67% of underrepresentations
      detected by CGH were expressed as clonal LOH at the respective loci. Clonal LOHs
      at 3p, 11p and 13q were detected in 2 cell lines each and were thus considered
      non-random. Immortal cells of 1 cell line (FK18B) revealed LOH at all 3 loci.
      Moreover, all immortal cell lines displaying allelic losses at one or more of
      these loci shared a severely dysplastic phenotype after organotypic culturing, as
      shown previously. Therefore, loss-of-function mutations of genes at these loci,
      eventually in combination, are potentially involved in the process of HPV
      mediated immortalization that is attended by a loss of terminal differentiation.
      Since chromosomal changes at these loci are also found in HPV-associated
      carcinomas in vivo, the HPV-transfected cell lines seem to provide a valuable
      model system for studying HPV-mediated carcinogenesis.

PMID- 9579581
TI  - Establishment and characterization of a murine osteosarcoma cell line (LM8) with
      high metastatic potential to the lung.
AB  - We established a murine osteosarcoma cell line (LM8) with high metastatic
      potential to the lung from murine Dunn osteosarcoma using 8 repeated Fidler's
      procedures. We performed the biological characterization of the LM8 and the
      maternal Dunn cell lines in vitro and in vivo. Morphologically, LM8 possesses
      many fillopodial protrusions, lamellipodial structures surrounding the cell
      surface and membrane ruffles suggesting enhanced cell motility. The increased
      matrix metalloproteinase (MMP) 2 activity of this cell line might help cell
      invasion after penetration of the endothelial (mesothelial) cell layer. This cell
      line exhibited high in vitro invasive activity when seeded onto the mesothelial
      cell monolayer. Higher expression of VEGF mRNA in this cell line might facilitate
      neovascularization at the site of metastasis, resulting in extremely high
      metastatic potency after i.v. injection. LM8 also showed a high metastatic
      incidence (7/7) to the lung even after s.c. transplantation into the back space
      of mice. This cell line can provide an excellent tool for studying inhibitory
      agents against pulmonary metastasis as well as the various important factors
      involved in metastasis of osteosarcoma.

PMID- 9579582
TI  - Interferon-alpha and -gamma inhibit the growth and neoplastic potential of v-src
      transformed human epithelial cells by reducing Src tyrosine kinase activity.
AB  - To investigate whether interferons (IFNs) selectively suppress the growth of
      solid tumor cells with elevated protein tyrosine kinase (PTK) activity, we
      evaluated the effect of recombinant IFN-alpha2a and IFN-gamma on the
      proliferative and neoplastic potentials triggered by p60v-src using v-src
      transformed HAG-1 human epithelial cells. When compared with control cells
      harboring the pSV2neo gene, the monolayer growth of v-src-transformed cell lines
      was inhibited by both recombinant IFNs, in a dose-dependent manner, whereas
      growth of ras-transfected cell lines was not affected. Moreover, IFNs markedly
      reduced the clonogenic growth of v-src-transformed cells in soft-agar rather than
      monolayer growth, suggesting the preferential activity of IFNs on anchorage
      independent growth. Pretreatment of cells with Src or the Src-like PTK inhibitor
      herbimycin A or radicicol, alleviated dose-dependently the growth-inhibitory
      activity of IFN-alpha2a against v-src-transformed cells, suggesting that IFNs may
      share a common inhibitory pathway with Src PTK inhibitors. Accordingly, like
      herbimycin A, IFNs were found to reduce tyrosine phosphorylation of p60v-src and
      suppressed in vitro p60v-src kinase activity in v-src-transformed cells. Our
      data, together with the fact that IFNs inhibit the growth potential driven by Src
      but not by activated Ras, suggest that inhibition of signal transduction pathway
      through Src to downstream transduction events may be a primary mechanism of IFN
      induced anti-prolifeative and anti-tumoral activity.

PMID- 9579583
TI  - Ecotropic C-type retrovirus of B16 melanoma and malignant transformation of
      normal melanocytes.
AB  - We reported previously that B16,JB/RH and JB/MS melanomas of C57BL/6 mice express
      the common melanoma-associated antigen (MAA) recognized by MM2-9B6 monoclonal
      antibody (MAb). This MAA is encoded by the env gene of an ecotropic MuLV-type
      retrovirus that somatically emerged in melanomas of C57BL/6 mice. The potential
      role of this melanoma-associated retrovirus (MelARV) in melanoma formation
      remains unknown and has not been previously investigated. To test this, normal
      melanocyte lines (melan-a and C57M) of C57BL/6 mice were infected with the MelARV
      produced by B16BL6 melanoma. Infection of these melanocytes with the MelARV was
      associated with the appearance of the MAA recognized by MM2-9B6 MAb. Most of the
      infected melanocyte sublines were able to grow only in the presence of 12-O
      tetradecanoylphorbol-13-acetate (TPA). Two infected melanocyte sublines showed
      morphological changes, were able to grow in the absence of TPA and, after
      inoculation into C57BL/6 mice, produced rapidly growing, highly pigmented tumors.
      These new melanomas, derived from the MelARV-infected melan-a and C57M
      melanocytes, were termed Meli-A1 and Meli-BL, respectively. Southern blot
      analysis of EcoRI- and HindIII-digested DNAs from these melanomas showed several
      retroviral insertion sites. One copy of MeIARV was found to be inserted at the
      end of the 6th leucine domain of the c-maf proto-oncogene, which encodes a basic
      region/leucine zipper transcription factor related to the AP-1 family that is
      able to form homodimers or heterodimers with Fos and Jun transcription factors.
      Our data indicate that c-maf is a common insertion site of MelARV in BL6, Meli-A1
      and Meli-BL melanomas, whereas no such insertion site was found in the
      melanocytes infected with MelARV but not malignantly transformed. Thus, our data
      imply that the ecotropic MelARV that somatically emerged in B16 and other
      melanomas of C57BL/6 mice may play a role in malignant transformation.

PMID- 9579584
TI  - Receptor tyrosine kinase Xmrk mediates proliferation in Xiphophorus melanoma
      cells.
AB  - Over-expression of the oncogenic receptor tyrosine kinase (RTK) Xmrk is
      sufficient to induce formation of hereditary malignant melanoma in the fish
      Xiphophorus. In the melanoma tissue as well as in a melanoma-derived cell line
      (PSM), the Xmrk protein shows strong tyrosine phosphorylation, indicating either
      ligand-independent or autocrine activation of its kinase domain. However, it is
      unknown whether the constitutively activated Xmrk receptor itself directly
      triggers the proliferative signals, thus leading to uncontrolled growth of the
      pigment cells. In order to evaluate the role of Xmrk in proliferation of melanoma
      cells, we inhibited its kinase activity by using a Xmrk specific tyrphostin. At a
      concentration of 10 microM, tyrphostin AG555 led to a decrease of the Xmrk
      induced DNA synthesis to 10% in NIH 3T3 Hm cells, whereas serum dependent 3H
      thymidine incorporation was unaffected. In fish melanoma cells, the drug
      efficiently blocked DNA synthesis and cellular growth. This anti-proliferative
      activity correlated with the potency of AG555 to inhibit Xmrk
      autophosphorylation, indicating that the Xmrk receptor is the major determinant
      of mitogenic signaling in Xiphophorus melanoma cells.

PMID- 9579585
TI  - Three-step tumor targeting via biotin-avidin interaction as a versatile system to
      elicit T cell-mediated, non-MHC-restricted cytotoxic activity against neoplastic
      cells.

PMID- 9579586
TI  - Possible routes of spread of carcinoma of the maxillary sinus to the oral cavity.
AB  - Carcinomas arising in the maxillary sinus, occasionally present clinically in the
      oral cavity along the occlusal ridge of the upper alveolus. The mechanism of this
      spread has not been investigated but it may resemble invasion of the mandible by
      oral carcinomas, which tend to invade the soft tissues rather than eroding
      through bone. In Britain, such patients are usually edentulous. This project
      examines deficiencies in the bony walls of the maxillary sinus to determine
      possible routes of spread. Maxillae were obtained from one side of 17 dissecting
      room cadavers, aged 71-95 years; 15 were edentulous. The roof of the maxillary
      sinus was removed in all specimens. Five maxillae were each cut into six slices,
      0.5 cm thick, in a vertical bucco-lingual plane. In all, soft tissues were
      removed by treatment in dilute bleach. Histological sections, cut in the
      horizontal plane, were prepared of a further three maxillae. Several possible
      routes were identified by which tumors could spread from the sinus to the oral
      cavity: 1) directly through foramina in its floor; 2) through numerous foramina
      in its floor to the marrow cavity of the alveolar process, which mostly contained
      fat amongst narrow bony trabeculae. (The marrow cavity, in turn, had numerous
      communications with the occlusal surface); 3) through foramina which carried
      branches of the superior alveolar nerves and vessels; 4) through deficiencies in
      the bony walls of the sinus at the neurovascular grooves and elsewhere.

PMID- 9579588
TI  - Morphometry of the midfacial complex in subjects with class III malocclusions:
      Procrustes, Euclidean, and cephalometric analyses.
AB  - The purpose of this study was to determine whether the morphology of the midface
      differed in subjects with a retrognathic midfacial appearance (Class III
      malocclusions) using a combination of morphometric and cephalometric analyses.
      After obtaining appropriate consent, lateral cephalographs of 133 children of
      European-American descent, ages 5-11 years, were compared: 73 had Class III
      malocclusion, 60 had normal (Class I) occlusion. The cephalographs were traced
      and subdivided into seven age- and sex-matched groups. Average geometries based
      upon seven nodes (pterygoid point, PTS; rhinion, RO; posterior nasal spine, PNS;
      midpalatal point, MPP; anterior nasal spine, ANS; subspinale, A; prosthion, Pr),
      scaled to an equivalent size, were compared using a Procrustes routine. Euclidean
      distance matrix analysis (EDMA) was employed to localize differences in
      morphology. Bivariate analyses on unscaled data utilizing nine linear and six
      angular measurements were also undertaken. Results from Procrustes and EDMA
      analyses indicated that although the overall midfacial configurations differed
      statistically (P < 0.05), only about half of the seven age sub-groups maintained
      significance. Similarly, only four of the nine linear measures (PNS-MPP, MPP-ANS,
      A-Pr and PTS-RO) and two of the six angular parameters (PTS-RO-ANS and ANS-A-Pr)
      tested were significantly different (P < 0.05). Therefore, midfacial morphometric
      variability and morphological diversity may mask statistical differences. It is
      concluded that the midface may be the defining craniofacial component in the
      final appearance of Class III malocclusions compared to other craniofacial
      components, including the cranial base and mandible.

PMID- 9579587
TI  - Anatomy of a "black eye": a newly described fascial system of the lower eyelid.
AB  - The anatomy of a black eye is examined in a series of cadaver dissections in
      which a previously unreported fascial system of the lower eyelid is identified.
      This fascia originates at the orbital rim, and is in continuity with the orbital
      septum and with the periosteum of the orbital floor and anterior maxillary wall.
      This fascia contributes to the thickened area along the orbital rim called the
      arcus marginale. At the level of the orbicularis oculi muscle, this fascia was
      noted microscopically to fuse with a fibrous septa of the superficial cheek fat.
      This creates one long continuous membrane from the orbital rim above to the cheek
      skin below. Dye injection techniques show that this membrane is impermeable and
      traps injected dye in the same place where a black eye forms. After periorbital
      injury, extravasated hemoglobin pigment is confined to the area above the
      cutaneous insertion of this membrane. This fascial system has been named the
      septum malaris: malar describes its origin along the orbital rim of the cheek,
      and septum further describes the partitioning nature of this ultra-thin membrane.

PMID- 9579589
TI  - Disc herniations in the young and end-plate vascularity.
AB  - The objective of this study was to determine the nature of the persistence of
      remnants of the original nutritive vascular canals within the vertebral body and
      correlate their existence with end-plate "weak spots." The body-disc region of 20
      lumbar vertebrae between the ages of birth and 22 years was examined
      histologically to study the vascularity of the end-plate cartilage and its fate
      at the end of vertebral growth. Observations indicate a regression of the
      vascular canals in the end-plate commencing in the first decade, with "scars"
      left by these canals visible as nodular areas. By the beginning of the third
      decade, herniation of the disc material into the weak spots was observed. It is
      apparent that these weak spots represent a route for the early formation of
      intrabody nuclear herniations at this age (Schmorl's nodes).

PMID- 9579590
TI  - Anatomic characteristics of the furcation and root surfaces of molar teeth and
      their significance in the clinical management of marginal periodontitis.
AB  - Treatment of periodontitis which involves the furcation area of molar teeth has
      always been a challenge. Sixty extracted human molar teeth were used for an
      anatomic study to clarify the possible morphologic factors which may affect the
      diagnosis, prognosis, and clinical management of periodontally involved teeth.
      Teeth were embedded in methylmethacrylate and cut in 70 microm cross sections
      from the cementoenamel junction to the apex. Cervical enamel projection, root and
      root trunk lengths, root proximities as well as depths of root concavities
      coronally, apically, and at the furcation roof were measured. Cervical enamel
      projections were observed in 30% of the teeth examined. The shortest root trunk
      was found at the buccal aspect of mandibular first molars, permitting furcation
      involvement at early stages of periodontal disease. The most apically located
      furcation was found at the distal site of maxillary first molars. Furcation roofs
      showed severe concavities and complex cementum morphology. Teeth exhibiting
      cervical enamel projection were found to have deeper root concavities compared to
      teeth without cervical enamel projection and mesial roots of mandibular molars
      possessed greater furcal concavities than distal roots. The presence of root
      concavities complicates the diagnosis of furcation involvement and restricts
      access of periodontal instruments, resulting in incomplete treatment. Furcation
      anatomy may also influence the long-term prognosis of the teeth by favoring the
      retention of bacterial deposits and making oral hygiene procedures almost
      impossible. The present study shows that knowledge of a tooth's unique anatomic
      characteristics is a prerequisite for effective periodontal therapy.

PMID- 9579591
TI  - Liliequist's membrane in minimally invasive endoscopic neurosurgery.
AB  - Liliequist's membrane, an arachnoid condensation extending from the upper border
      of the dorsum sellae to the anterior edge of the mammillary bodies and formerly a
      relatively insignificant structure, has been found to be extremely important in
      the neuroendoscopic management of hydrocephalus. Failure to open this membrane
      can lead to the failure of third ventriculostomies.

PMID- 9579592
TI  - Dissecting room problem: prevalence of latex allergy among medical students.
AB  - Latex gloves are in widespread use among preclinical medical and dental students
      in the dissecting room. Increasing numbers of cases of severe latex sensitivity
      are being reported. This study was carried out to assess the size of this problem
      among preclinical and clinical students. First-year students (196) and fifth-year
      students (155) of the United Medical and Dental Schools of Guy's and St. Thomas's
      Hospitals (UMDS) were asked to complete a questionnaire about symptoms related to
      allergy to latex gloves and associated risk factors. The prevalence of all self
      reported symptoms was 9.6% overall with no significant difference between first-
      and fifth-year students. The prevalence of rash was significantly different; 2.6%
      in first-year and 8.5% in fifth-year students. Of those who reported symptoms,
      there was a significant excess of females and of individuals with eczema, hay
      fever, or a family history of atopic conditions, compared with those without
      symptoms. There was no difference between racial groups and no demonstrable link
      with a history of food allergy, previous surgery, or sensitivity to household
      rubber products. Only 2 of the 29 individuals with symptoms reported for skin
      prick testing, one of whom demonstrated Type I hypersensitivity.

PMID- 9579593
TI  - Remarkable placenta.
AB  - This paper reviews the principle features of human placenta structure and
      development, and it highlights areas of needed future research. The complexity of
      placental histology is discussed and comparison of the human placenta with other
      mammalian taxa is made. A more widespread appreciation of the value of studying
      this challenging organ and a more profound understanding of the regulation of the
      placental transport functions is advocated. Simple, routine examination of the
      placenta should be resurrected.

PMID- 9579594
TI  - Problem in diagnostic imaging: pancreaticoduodenal arcade in splanchnic arterial
      stenosis.
AB  - This paper features a problem in diagnostic imaging in which a pre-transplant
      abdominal angiogram of a potential liver recipient shows filling of the hepatic
      artery via the superior mesenteric artery and the pancreaticoduodenal arcade. The
      routing of this unusual supply to the liver is explained by careful study of
      abdominal aortic angiograms and a sagittal MRI made through the aorta.

PMID- 9579595
TI  - Bilateral four-headed biceps brachii muscles: the median nerve and brachial
      artery passing through a tunnel formed by a muscle slip from the accessory head.
AB  - Bilateral four-headed biceps brachii muscles were observed in the dissected
      cadaver of a 95-year-old Japanese woman. The third head on both sides originated
      from the humerus at the insertion of the coracobrachialis and inserted into the
      distal part of the biceps brachii and the proximal part of the common biceps
      tendon on the ipsilateral side. The fourth head on both sides arose from a thin
      fibrous origin from the intertubercular sulcus and the insertion of the
      pectoralis major, and inserted into the confluence of the biceps brachii and the
      third head. This anomaly is relatively rare. Moreover, the left third head gave
      off a muscle slip into the posterior fascia of the pronator teres, forming a
      tunnel. The median nerve and the brachial artery passed through the tunnel, where
      the nerve and artery seemed to be compressed. The possible production of clinical
      symptoms, given the anatomy, is discussed.

PMID- 9579596
TI  - Scholarly activities within the AACA: a survey report. American Association of
      Clinical Anatomists.

PMID- 9579597
TI  - Structure of the subfornical organ: a review.
AB  - In this review, the light microscopic and fine structural characteristics of
      neurons, axons, dendrites, glial cells, and capillaries and their topography
      within the subfornical organ are summarized, with an emphasis on recent findings.
      Structure-function relationships are discussed whenever possible and put into
      perspective in a concluding section.

PMID- 9579598
TI  - The subcommissural organ.
AB  - The subcommissural organ (SCO) is a phylogenetically ancient and conserved
      structure. During ontogeny, it is one of the first brain structures to
      differentiate. In many species, including the human, it reaches its full
      development during embryonic life. The SCO is a glandular structure formed by
      ependymal and hypendymal cells highly specialized in the secretion of proteins.
      It is located at the entrance of the aqueduct of Sylvius. The ependymal cells
      secrete into the ventricle core-glycosylated proteins of high molecular mass. The
      bulk of this secretion is formed by glycoproteins that would derive from two
      different precursors of 540 and 320 kDa and that, upon release into the ventricle
      aggregate, form a threadlike structure known as Reissner's fiber (RF). By
      addition of newly released glycoproteins to its proximal end, RF grows caudally
      and extends along the aqueduct, fourth ventricle, and the whole length of the
      central canal of the spinal cord. RF material continuously arrives at the dilated
      caudal end of the central canal, known as the terminal ventricle or ampulla. When
      reaching the ampulla, the RF material undergoes chemical modifications,
      disaggregates, and then escapes through openings in the dorsal wall of the
      ampulla to finally reach local blood vessels. The SCO also appears to secrete a
      cerebrospinal fluid (CSF)-soluble material that is different from the RF material
      that circulates in the ventricular and subarachnoidal CSF. Cell processes of the
      ependymal and hypendymal cells, containing a secretory material, terminate at the
      subarachnoidal space and on the very special blood capillaries supplying the SCO.
      The SCO is sequestered within a double-barrier system, a blood-brain barrier, and
      a CSF-SCO barrier. The function of the SCO is unknown. Some evidence suggests
      that the SCO may participate in different processes such as the clearance of
      certain compounds from the CSF, the circulation of CSF, and morphogenetic
      mechanisms.

PMID- 9579599
TI  - Ependymal and choroidal cells in culture: characterization and functional
      differentiation.
AB  - During the past 10 years, our teams developed long-term primary cultures of
      ependymal cells derived from ventricular walls of telencephalon and hypothalamus
      or choroidal cells (modified ependymal cells) derived from plexuses dissected out
      of fetal or newborn mouse or rat brains. Cultures were established in serum
      supplemented or chemically defined media after seeding on serum-, fibronectin-,
      or collagen-laminin-coated plastic dishes or semipermeable inserts. To identify
      and characterize cell types growing in our cultures, we used morphological
      features provided by phase contrast, scanning, and transmission electron
      microscopy. We used antibodies against intermediate filament proteins (vimentin,
      glial fibrillary acidic protein, cytokeratin, desmin, neurofilament proteins),
      actin, myosin, ciliary rootlets, laminin, and fibronectin in single or double
      immunostaining, and monoclonal antibodies against epitopes of ependymal or
      endothelial cells, to recognize ventricular wall cell types with immunological
      criteria. Ciliated or nonciliated ependymal cells in telencephalic cultures,
      tanycytes and ciliated and nonciliated ependymal cells in hypothalamic cultures
      always exceeded 75% of the cultured cells under the conditions used. These cells
      were characterized by their cell shape and epithelial organization, by their
      apical differentiations observed by scanning and transmission electron
      microscopy, and by specific markers (e.g., glial fibrillary acidic protein,
      ciliary rootlet proteins, DARPP 32) detected by immunofluorescence. All these
      cultured ependymal cell types remarkably resembled in vivo ependymocytes in terms
      of molecular markers and ultrastructural features. Choroidal cells were also
      maintained for several weeks in culture, and abundantly expressed markers were
      detected in both choroidal tissue and culture (Na+-K+-dependent ATPase, DARPP 32,
      G proteins, ANP receptors). In this review, the culture models we developed
      (defined in terms of biological material, media, substrates, duration, and
      subculturing) are also compared with those developed by other investigators
      during the last 10 years. Focusing on morphological and functional approaches, we
      have shown that these culture models were suitable to investigate and provide new
      insights on (1) the gap junctional communication of ependymal, choroidal, and
      astroglial cells in long-term primary cultures by freeze-fracture or dye transfer
      of Lucifer Yellow CH after intracellular microinjection; (2) some ionic channels;
      (3) the hormone receptors to tri-iodothyronine or atrial natriuretic peptides;
      (4) the regulatory effect of tri-iodothyronine on glutamine synthetase
      expression; (5) the endocytosis and transcytosis of proteins; and (6) the
      morphogenetic effects of galactosyl-ceramide. We also discuss new insights
      provided by recent results reported on in vitro ependymal and choroidal
      expressions of neuropeptide-processing enzymes and neurosecretory proteins or
      choroidal expression of transferrin regulated through serotoninergic activation.

PMID- 9579600
TI  - Scanning electron microscopy of central nervous system cerebrospinal-fluid
      contacting surfaces: a bibliography (1963-1995).
AB  - This bibliography is compiled to assist in locating papers related to the
      application of scanning electron microscopy (SEM) to cerebrospinal-fluid
      contacting surfaces in vertebrates. The use of SEM by neuroscientists has
      continued apace since the publication of the first bibliography in 1980. SEM
      studies now include more than 50 species of vertebrates and range from
      cyclostomes to humans; they encompass development from embryo to senescence and
      concern both normal and pathologic morphology. Although remarkable strides have
      been made toward a greater understanding of many aspects of the structure and
      function of cerebrospinal-fluid-contacting surfaces, many significant problems
      await the judicious application of scanning electron microscopy.

PMID- 9579601
TI  - The Sterling-Gallant new allotropic form of silver detected in biological
      preparations containing cysteine.

PMID- 9579602
TI  - Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE
      guidelines. International Society of Hematotherapy and Graft Engineering.
AB  - In concert with the International Society of Hematotherapy and Graft Engineering
      (ISHAGE), we previously described a set of guidelines for detection of CD34+
      cells based on a four-parameter flow cytometry method (CD45 FITC/CD34 PE
      staining, side and forward angle light scatter). With this procedure, an absolute
      CD34+ count is generated by incorporating the leukocyte count from an automated
      hematology analyser (two-platform method). In the present study, we modified the
      basic ISHAGE method with the addition of a known number of Flow-Count
      fluorospheres. To reduce errors inherent to sample washing/centrifugation, we
      implemented ammonium chloride lyse, no-wash no-fix sample processing. These
      modifications convert the basic protocol into a single-platform method to
      determine the absolute CD34 count directly from a flow cytometer and form the
      basis of the Stem-Kit from Coulter/Immunotech. A total of 72 samples of
      peripheral blood, apheresis packs, and cord blood were analysed and compared
      using the ISHAGE protocol with or without the addition of fluorescent
      microspheres. Comparison of methods showed a high correlation coefficient
      (r=0.99), with no statistically significant difference or bias between methods (P
      > 0.05). Linearity of the absolute counting method generated an R2 value of 1.00
      over the range of 0-250/microl. Precision of the absolute counting method
      measured at three concentrations of CD34+-stabilised KG1 a cells (Stem-Trol,
      COULTER) generated a coefficient of variation (C.V.) ranging from 4% to 9.9%. In
      a further modification of the single-platform method, the viability dye 7-amino
      actinomycin D was included and demonstrated that both viable and nonviable CD34+
      cells could be identified and quantitated. Together, these modifications combine
      the accuracy and sensitivity of the original ISHAGE method with the ability to
      produce an absolute count of viable CD34+ cells. It is the accurate determination
      of this value that is most clinically relevant in the transplant setting. These
      modifications may improve the interlaboratory reproducibility of CD34
      determinations due to the reduction in sample handling and calculation of
      results.

PMID- 9579603
TI  - FMC7 antigen expression on normal and malignant B-cells can be predicted by
      expression of CD20.
AB  - Most antibody panels proposed for flow cytometric immunophenotyping of non
      Hodgkin's lymphomas and chronic lymphoid leukemias include anti-CD20 and FMC7
      antibodies. As in our experience, reactivity of B-cells with these antibodies
      seemed to be correlated, we evaluated whether the simultaneous use of anti-CD20
      and FMC7 antibodies is justified. Using flow cytometry, we measured the binding
      of these 2 antibodies to the B-cells of 67 bone marrow aspirates, 31 lymph node
      biopsies, 18 peripheral blood specimens, and 12 tissue samples from other
      locations. The diagnoses included 50 cases without overt abnormalities, 5
      reactive lymphadenopathies, 56 lymphomas and chronic lymphoid neoplasias, and 17
      cases with other malignancies. Although CD20 expression was consistently higher,
      we observed a significant and strong correlation between CD20 and FMC7 antigen
      expression on B-lymphocytes, irrespective of the nature of the sample or disease
      (r=0.910; P < 0.001). Moreover, FMC7 antigen expression on B-cells could be
      predicted by CD20 expression with a sensitivity of 96%, a specificity of 94% and
      an efficiency of 96%. Our results show that although differing in intensity,
      expression of CD20 on B-cells closely parallels that of FMC7 antigen. We,
      therefore, conclude that little additional information is revealed by using FMC7
      in immunophenotyping of non-Hodgkin's lymphomas or chronic lymphoid leukemias if
      intensity of CD20 expression is taken into consideration.

PMID- 9579604
TI  - Differentiation of low-grade non-Hodgkin's lymphomas using paraffin sections by
      image processing.
AB  - In a previous study, we were able to demonstrate that the differentiation of low
      grade non-Hodgkin's lymphomas (NHLs) using digital image analysis of touch
      imprints obtained from native tumor tissue is feasible. The availability of touch
      imprints in routine diagnostics, however, is restricted. Therefore, we extended
      our studies toward paraffin sections being used as routine material for
      histological diagnoses. To identify five types of NHL classified according to the
      Revised European American Lymphoma classification, paraffin sections (n=53) of
      NHL and 9 reactive lymphoid tissues (RLTs) were scanned with a color-video-based
      microscope system and analyzed by digital image processing. A reliable division
      between benign and neoplastic lymphoproliferations was achieved. We were able to
      identify 78% of RLTs as benign and 94% of NHLs as neoplastic. The average
      probability of correct identification into the six subgroups was 66%. In detail,
      78% of RLTs, 50% of chronic lymphocytic lymphomas and MALT-type lymphomas, 72% of
      mantle cell lymphomas, and 67% of follicle center cell lymphoma were classified
      correctly. Although the method of subclassifying or identifying NHLs on the basis
      of a computer-mediated assay is still not usable in daily practice, we show that
      a reliable differentiation between reactive and neoplastic lymphoproliferative
      lesions can be achieved by analysis of paraffin sections with high-resolution
      image analysis and that it is possible to define nuclear structures by
      identifying subtypes of NHL.

PMID- 9579605
TI  - Flow cytometry with or without cytochemistry for the diagnosis of acute
      leukemias?
AB  - Ninety-three (93) cases of acute leukemia were assessed using flow cytometry and
      cytochemistry and assigned to one of four categories: myeloid, lymphoid,
      biphenotypic, and non-diagnostic. In leukemias designated as ALL or AML by both
      methodologies, there was lineage agreement in all but 3 of 71 cases (95.8%).
      However, when nondiagnostic or biphenotypic diagnoses made by either methodology
      were included, complete agreement occurred in only 77.4% of cases. Of 37 cases
      designated myeloid origin by flow cytometry, 33 (89.2%) were read as myeloid by
      cytochemistry. The four discordant diagnosis were read as lymphoid (2) or as non
      diagnostic (2). Eighty percent of lymphoid leukemias were diagnosed as such by
      both flow cytometry and cytochemistry; one early B cell ALL was diagnosed as
      myeloid and 8 as non-diagnostic. Fifty percent (50%) of flow cytometry defined T
      cell ALL were considered non-diagnostic by cytochemistry as compared to 17% of
      the total ALL group. Of the remaining four designated non-T cell ALL by flow
      cytometry and non-diagnostic by cytochemistry, three were read by flow cytometry
      to be standard pre-B ALL and one an early B-cell ALL. Only 2/9 leukemias
      considered biphenotypic by flow were identified as such by cytochemistry. Given
      (1) the potential importance of non-lineage expression in the prognosis of
      myeloid and lymphoid leukemias, (2) cytochemistry's impaired ability to diagnose
      biphenotypic, T-cell, and promyelocytic leukemias, and (3) the increased costs
      incurred in diagnosis when both modalities are used, perhaps it is time to re
      examine the utility of performing both flow cytometry and cytochemistry as
      initial testing for leukemia categorization.

PMID- 9579606
TI  - Combined metaphase, interphase cytogenetic, and flow cytometric analysis of DNA
      content of pediatric acute lymphoblastic leukemia.
AB  - Eleven pediatric acute lymphoid leukemia patients were investigated for
      chromosomal aneuploidy by interphase cytogenetics using chromosome specific
      (peri)centromeric probes for all the somatic and sex chromosomes. Results were
      compared with metaphase cytogenetic and flow cytometric derived DNA aneuploidy
      data. Experiments performed on normal human cells using chromosome specific
      (peri)centromeric probes indicated that disomy could be recognized in a range of
      89.1+/-2.7% (12.9)-96.8+/-0.2% (0.9) for the somatic chromosomes and in 98.1+/
      0.4% (1.3) for the sex chromosomes. Using the cutoff level of the mean false
      monosomy and trisomy in the control cells +2 S.D., chromosome loss or gain for
      the somatic chromosomes could be revealed beyond a clonal ratio of 3.6-13.2% and
      1.1-6.8%, respectively. The same value for the sex chromosomes was 3.5% and 0%,
      respectively. In 5 of 11 patients the leukemic cells proved to be diploid with
      all three methods at both gross DNA and chromosome levels. Interphase
      cytogenetics revealed chromosome loss or gain in all of the remaining six
      patients, however, the metaphase analysis indicated numerical aberration in only
      two patients. In one of them only the increased chromosome number could have been
      detected without identifying the chromosomes involved and in the other one the
      two methods indicated trisomy for a different chromosome. Flow cytometric data
      showed aneuploidy in three of the six aneuploid leukemia patients. The results
      suggest that interphase cytogenetics might be more accurate compared with flow
      cytometry and metaphase analysis to reveal aneuploidy.

PMID- 9579607
TI  - Flow cytometry description of a novel CD3-/CD7+ intraepithelial lymphocyte subset
      in human duodenal biopsies: potential diagnostic value in coeliac disease.
AB  - Intraepithelial lymphocytes (IEL) represent a heterogeneous cellular compartment
      of unknown functions and controversial ontogeny. Previous observations in humans
      indicate that the majority of IEL subsets express the CD3 complex associated with
      either the alphabeta or the gammadelta T-cell receptor components, and describe
      the characteristic increase of CD3+TCRgammadelta+ IEL in coeliac disease. In the
      present work, we analyze the surface antigen expression of intraepithelial
      lymphocytes isolated from duodenal biopsies of control subjects and coeliac
      disease patients. We describe a CD3-CD7 + IEL subset frequently found in control
      subjects (41.41+/-21.8), with the following features: 1) most of these cells are
      CD45R0+ CD103+ and CD44- CD28- CD5-; 2) a significant percentage express CD56
      (44.7%+/-21.3), CD2 (55.1%+/-16.2), and CD94 (16.2%+/-7.3). Furthermore, they are
      CD122+ and CD25-; 3) this CD3- IEL subset exhibit an activated phenotype
      expressing higher levels of CD69, CD103, and CD38 than the CD3+ subset.
      Interestingly, this CD3- subset is drastically reduced in CD patients (2.2+/-2.9
      in active disease, 6.3+/-4.6 in treated patients versus 41.4+/-21.8 in control
      subjects). The imbalanced ratio "increased TCRgammadelta versus decreased CD3-
      CD7+" is a permanent finding in CD patients following clinical and histological
      remission. This parameter might provide helpful diagnostic information (easily
      obtained by 3-color FCM from diagnostic biopsies), and suggest a potential
      implication in the pathogenesis of coeliac disease.

PMID- 9579608
TI  - Peripheral blood lymphoid subsets and long-term clinical course of kidney
      recipients: a longitudinal study.
AB  - A longitudinal study of peripheral blood lymphocyte subsets was performed in 23
      renal allograft recipients treated with prophylactic antilymphocyte antibodies,
      CsA, and steroids. At day 0 samples were obtained before transplantation (Tx),
      and afterwards at months +1, +3, +6, +9, +12, +24, +36, and +48. In all patients,
      after the depletion of lymphoid subsets during antilymphocyte antibody treatment,
      CD8+ lymphocytes recovered and reached higher values than those observed prior to
      Tx. This was mainly due to an increase in CD8+CD45RA+ lymphocytes; in contrast,
      the levels of "memory" CD4+ T cells and the CD4+CD62L+ subset remained low during
      all the follow-up period. In patients with preserved graft function (n=14) (with
      creatinine levels below 200 micromol/mL), the initial, relative decrease in CD4+
      T cells was never reversed and the recovery of CD8+ lymphocytes started early.
      They also presented a peak of HLA-DR antigen expression at 1 month, not observed
      in those patients displaying a suboptimal graft function. At 1 month, the
      patients with suboptimal graft function (n=9) (with creatinine levels above 200
      micromol/mL) showed higher number of CD4+ T cells, delayed recovery of CD8+
      lymphocytes, and higher percentage of activated lymphocytes from month +3 on than
      well-functioning kidney recipients. Both CD8+ lymphocytes and HLA-DR+ T cells,
      found at month + 1 post-Tx, were negatively correlated with the concentration of
      creatinine along the follow-up. Interestingly, the mean percentage of CD4+CD25+ T
      cells found 36 and 48 months after Tx were positively correlated with creatinine
      concentration at these times. These findings indicate that variations in the
      distribution of lymphocyte subsets are related with a long-term graft outcome.
      Within the first month after Tx, a rapid recovery of CD8+ lymphocytes, but not of
      CD4+ T cells, and a peak of HLA-DR expression, are associated with a good graft
      function. In contrast, long-term expression of activation markers is related with
      renal dysfunction.

PMID- 9579609
TI  - Knowledge of childhood asthma among medical students.
AB  - As future health care providers medical students should acquire an adequate
      knowledge of bronchial asthma before graduation from medical school. The aim of
      this study was to assess whether knowledge about childhood asthma increased
      during the medical course. The 590 medical students enrolled in the School of
      Medical Sciences, University of Science Malaysia during the 1995/96 session were
      studied utilizing a validated questionnaire. There was a significant increase in
      the mean total scores from 11 (95% CI 10.5-11.6) in Year 1 to 23.4 (95% CI 22.9
      24) in Year 5. Questions about symptoms of asthma, pathogenesis of airway
      narrowing during acute exacerbations, preventive and reliever medications, side
      effects of steroids, addiction to asthma drugs and assessment of severity
      revealed a progressive increase in knowledge over the five years. Among 5th year
      medical students 44.6% named infection and 65.1% named exercise as two common
      triggers of childhood asthma; only 30.1% could name two prophylactic drugs for
      asthma. Although the asthma knowledge of medical students increased progressively
      during the five year curriculum, their knowledge regarding trigger factors and
      preventive medications were deficient. As childhood asthma affects some 10% of
      Malaysian children its importance requires greater emphasis in the medical
      curriculum.

PMID- 9579610
TI  - Aeroallergen sensitivity of Thai patients with allergic rhinitis.
AB  - The aim of this study was to determine the aeroallergen sensitivity of allergic
      rhinitis patients. A total of 100 cases (female: 59, male: 41, aged between 10-59
      years, mean age 27.9 years) who were diagnosed with allergic rhinitis by history
      and clinical presentation, underwent a prick skin test with 30 aeroallergens, and
      the important sensitizing allergens were assessed. Skin test reactivity showing >
      or = 3 mm wheal with erythema as the positive skin test, was recorded. The
      results of patients with positive skin tests follow. TREES: acacia 19%, mango
      16%, coconut 12%. GRASSES: bermuda 17%, johnson 21%, timothy 16%, bahia 16%
      orchard 18%. WEEDS: pigweed 16%, kochia 14%. MOLDS: alternaria 11%, cladosporium
      11%, aspergillus 12%, penicillium 16%, helminthosporium 16%, botrytis 15%,
      rhodotorula 20%, fusarium 26%, curvularia 26%, smut mix 11%, rust 9%. EPIDERMALS:
      cat 29%, dog 28%, feathers 37%. INDOOR ALLERGENS: house dust 72%, D.
      pteronyssinus 76%, D. farinae 79%, American cockroach 60%, German cockroach 41%,
      kapok 30%. Eighty-five percent of patients sensitive to house dust mites were
      positive to both D. pteronyssinus and D. farinae, indicating substantial cross
      reactivity. The study shows that the house dust mite and the cockroach are
      important aeroallergen sensitizers among the Thai population, since more than
      half the patients were skin-test positive to the house dust mite and the
      cockroach.

PMID- 9579611
TI  - Comparison of dengue virus antigens in sera and peripheral blood mononuclear
      cells from dengue infected patients.
AB  - The presence of dengue virus antigens in acute sera and peripheral blood
      mononuclear cells (PBMC) from dengue infected patients were determined by a
      biotin-streptavidin enzyme-linked immunosorbent assay (BS-ELISA). The frequency
      of the antigens detected in PBMC was higher than that in sera (53.8% vs 18.9%).
      In comparison with sera, the detection rate in PBMC was greater than six times: 7
      cases were positive only in sera whereas 44 cases were positive only in PBMC, p <
      0.001. The presence of the antigens in the sera did not depend on the severity of
      the disease, i.e. dengue fever, dengue hemorrhagic fever (grades I and II) or
      dengue shock syndrome (grades III and IV). In contrast, the presence of the
      antigens in PBMC increased from 36.8% to 100% when the infection was more severe.
      The dengue virus antigens could be detected in the samples collected between day
      2 and day 7 after onset of the disease with the highest rate of detection (68.8%)
      in PBMC collected on day 4. The data suggest the use of PBMC with access to the
      appropriate acute-phase specimen for detection of dengue virus antigens.

PMID- 9579612
TI  - Anti-HIV antibody titer: an alternative supplementary test for diagnosis of HIV-1
      infection.
AB  - The diagnosis of HIV infection is based on screening of HIV antibodies and
      confirmed by a more specific supplementary test. The most common confirmation
      test is Western blot, which is expensive, time consuming and subject to technical
      skill. The present study was carried out to evaluate whether the anti-HIV-1
      antibody titer is valid as a supplementary test for diagnosis of HIV-1 infection.
      Anti-HIV-1 antibody titers of 2,414 anti-HIV-1 positive sera determined by the
      particle agglutination (PA) method were analysed in comparison with the Western
      blot analysis. The Western blot negative result was found in 11 of 2,414 (0.46%)
      anti-HIV-1 positive sera, these sera also gave negative anti-HIV by ELISA. The PA
      titers of these sera were found in the range of 16 to 64. Seventeen samples
      (0.70%) with anti-HIV-1 in the titer range of 16 to 256 showed indeterminate
      Western blot analysis. The rest, 2,386 of these 2,414 sera (98.84%), were shown
      to be positive by Western blot. However, all of the 2,356 sera with antibody
      titers > or = 512 (97.6%) demonstrated positive Western blot results. Five cases
      among the 17 (29.4%) indeterminate sera were examples of early seroconversion of
      HIV infection, which were confirmed in follow up specimens. The results suggest
      that only the samples with antibody titers < 512 are required to be confirmed for
      HIV infection by Western blot. It is possible that early seroconversion may be
      inferred from anti-HIV titers. Therefore, in order to reduce time and cost, the
      PA anti-HIV titer can be used as an alternative supplementary test for diagnosis
      of HIV-1 infection in most positive screened anti-HIV samples. Western blot is
      needed for testing in only a few cases.

PMID- 9579613
TI  - Diagnosis of perinatal HIV-1 infection by in-house PCR.
AB  - A study on how to apply PCR as a diagnostic test for the infants born to HIV-1
      infected mothers is described. All steps including clinical care, blood sampling,
      specimen processing and PCR analysis were carried out using native facilities and
      personnel. An open cohort of 130 children was evaluated at birth, 1, 6, 9, 15,
      and 18 months of age. Definite infection status was assessed by clinical and
      serological data during an 18 months of follow up period. PCR results were
      reported as positive or negative when at least 2 concordant data were denoted.
      This in-house PCR, compared to known infection status, gave 100% sensitivity and
      94.4% specificity within 6 months after birth. On the other hand, clinical
      diagnosis could identify only the infected infants at 9 months of age. The HIV-1
      transmission rate from mother to infant was 23.2%. Though this PCR was not at an
      optimal level of specificity, it was still beneficial to identify uninfected
      infants in the first year of their lives and avoid unnecessary medical care.
      Here, we report an in-house PCR that offers good performance at low cost for the
      diagnosis of HIV-1 vertical transmission.

PMID- 9579614
TI  - Diagnosis of enteric fever caused by Salmonella spp. in Vietnam by a monoclonal
      antibody-based dot-blot ELISA.
AB  - Enteric fever caused by Salmonella spp. is prevalent in Vietnam. None of the
      currently available diagnostic methods meets the ideal criteria on rapidity,
      simplicity, sensitivity, specificity, cost-effectiveness and practicality for
      developing areas. In this study, a recently developed monoclonal antibody-based
      dot-blot ELISA was used in comparison with the hemoculture method and the
      classical Widal test for diagnosis of salmonellosis in 171 Vietnamese patients
      presenting with clinical features of enteric fever. Urine samples of 50 healthy
      counterparts were used as negative controls. Salmonella spp. were isolated from
      77 of 171 patients (45%) while 98 and 111 patients were positive by dot-blot
      ELISA and Widal test, respectively. The diagnostic sensitivity, specificity,
      accuracy, positive predictive value and negative predictive value of the ELISA
      performed on three serial urine samples collected at 2 hour intervals of the 171
      patients were 92.2%, 71.3%, 80.7%, 72.4% and 91.8%, respectively when compared
      with the culture method. The Widal test performed on acute and convalescence
      serum samples showed 87.0%, 46.8%, 68.4%, 60.4% and 83.3% diagnostic sensitivity,
      specificity, accuracy, and positive and negative predictive values, respectively
      when compared with the bacterial culture method. Kappa coefficience revealed very
      good agreement beyond chance between the MAb-based ELISA and the culture method.
      The ELISA was not reactive when tested on urine samples of 50 healthy individuals
      which indicates 100% specificity. The Salmonella antigenuria of the patients as
      detected by ELISA lasted 10.3+/-3.9 days after initiating antibiotic treatment.
      The MAb-based dot-blot ELISA is easy to perform. It is rapid, sensitive,
      specific, inexpensive, and non-invasive and does not require equipment, thus is
      suitable for developing areas. It can detect acute/recent infection and can be
      used for evaluation of the efficacy of the treatment.

PMID- 9579615
TI  - Antigenic components of somatic extract from adult Fasciola gigantica recognized
      by infected human sera.
AB  - The antigenic components of Fasciola gigantica somatic extract were revealed by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      immunoblotting technique using sera from patients with F. gigantica infection,
      patients with clinically diagnosed fascioliasis, patients with other
      infections/illness and healthy adults. By SDS-PAGE, it was found that the somatic
      product comprised more than 22 polypeptides. Immunoblotting analysis revealed at
      least 13 components which were strongly recognized by sera of patients with
      fascioliasis. These antigenic components had molecular weights ranging from less
      than 14.4 to more than 94 kDa. One antigenic component, i.e. 38 kDa was found to
      give a consistent reaction with sera of patients with fascioliasis (100%
      sensitivity and 96.7% specificity). The finding suggests that the 38 kDa
      components may be a potential diagnostic antigen for fascioliasis.

PMID- 9579616
TI  - Treatment of intrabony defects by different surgical procedures. A literature
      review.
AB  - This article reviews studies presented during the last 20 years on the surgical
      treatment of intrabony defects. Treatments include open flap debridement alone
      (OFD); OFD plus demineralized freeze-dried bone allograft (DFDBA), freeze-dried
      bone allografts (FDBA), or autogenous bone; and guided tissue regeneration (GTR).
      The review includes only studies that presented baseline and final data on
      probing depths, intrabony defect depths as measured during surgery, clinical
      attachment level (CAL) gain, and/or bone fill. Some reports were case studies and
      some controlled studies comparing different treatments. In order to assess what
      can be accomplished in terms of pocket reduction, clinical attachment level gain,
      and bone fill with the various treatment modalities, data from studies of each
      treatment category were pooled for meta-analysis in which the data from and power
      of each study were weighted according to the number of defects treated. In
      addition, where there were data for each individual defect treated, these were
      used for simple regression analysis evaluating the influence of intrabony defect
      depth on treatment outcome in terms of CAL gain and bone fill. This was done in
      an effort to assess some predictability of the outcome of the various treatments.
      OFD alone resulted in limited pocket reduction, CAL gain averaged 1.5 mm and bone
      fill 1.1 mm. Bone fill, but not CAL gain, correlated significantly to the depth
      of the defect (R=0.3; P < 0.001), but the regression coefficient was only 0.25.
      OFD plus bone graft resulted in limited pocket reduction. CAL gain and bone fill
      averaged 2.1 mm. Bone fill showed a somewhat stronger correlation to defect depth
      than following OFD alone (R=0.43; P < 0.001) with a regression coefficient of
      0.37. GTR resulted in significant pocket reduction, CAL gain of 4.2 mm, and bone
      fill averaging 3.2 mm. CAL gain and bone fill correlated significantly (P <
      0.001) to defect depth (R=0.52 and 0.53 respectively) with the largest regression
      coefficients (0.54 and 0.58 respectively) among the three treatment modalities.
      By comparing outcomes following the various treatments it became obvious that to
      benefit from GTR procedures, the intrabony defect has to be at least 4 mm deep.

PMID- 9579617
TI  - Uncontrolled diabetes hinders bone formation around titanium implants in rat
      tibiae. A light and fluorescence microscopy, and image processing study.
AB  - This study examined the influence of diabetes mellitus on bone formation around
      cylindrical titanium (Ti) implants (1.0 mm in diameter and 1.5 mm in length)
      inserted transcortically and extending into the medullary canal of rat tibiae
      using light and fluorescence microscopies and image processing. Forty-eight male
      Wistar King A rats (age 5 weeks) were used in this experiment. Streptozotocin was
      injected intraperitoneally to induce diabetes and the serum glucose concentration
      was checked to ensure the induction of diabetes prior to implant placement and at
      the time of sacrifice. The animals were sacrificed 7, 28, 56, or 84 days after
      placement. Toluidine blue-stained undecalcified sections were prepared for
      histological observation and image analysis. The Ti implants in the control group
      became increasingly encapsulated with a bone layer. The implants in the diabetes
      induced (DI) group were also surrounded with a thin bone layer. Abundant
      adipocytes were observed in the DI group as compared with the control group.
      Quantitative evaluation indicated that the control group showed a significantly
      higher percent of bone contact, and thickness of surrounding bone and area than
      the DI group. Consequently, the present study suggests that uncontrolled diabetes
      would hinder bone formation around Ti implants in rats.

PMID- 9579618
TI  - Immediate loading of titanium plasma-sprayed implants: an histologic analysis in
      monkeys.
AB  - Aim of this study was to evaluate peri-implant tissue reactions to immediately
      loaded titanium plasma-sprayed implants in Macaca fascicularis monkeys. A total
      of 48 titanium plasma-sprayed implants were inserted (24 in the posterior maxilla
      and 24 in the posterior mandible). A metal superstructure was cemented 3 days
      after implant insertion on 24 implants (12 in the maxilla and 12 in the mandible)
      (test implants). The remaining 24 implants (12 in the maxilla and 12 in the
      mandible) were left unloaded (control implants). Nine months after implant
      placement a block section was carried out, the defect filled with non-resorbable
      hydroxyapatite, and all 48 implants retrieved. The implants were treated to
      obtain thin ground sections. Three slides were cut for each implant and examined
      under normal and polarized light and a morphometrical analysis done. All implants
      were covered by bone under light microscopy. The histomorphometrical analysis
      demonstrated that in test implants, the bone-implant contact percentage was 67.3%
      (+/-7.6%) in the maxilla, and 73.2% (+/-5.9%) in the mandible; in control
      implants the percentages were, respectively, 54.5% (+/-3.3%) and 55.8% (+/-6.5%).
      In the test implants the bone around the implants tended to have a more compact
      appearance. In conclusion, our study demonstrated that in test implants the bone
      implant contact percentage was significantly greater than in the controls (P <
      0.01) and no fibrous connective tissue was present at the interface.

PMID- 9579619
TI  - Reproducibility and validity of the assessment of clinical furcation parameters
      as related to different probes.
AB  - The aim of this study was to investigate the reliability of the assessment of
      clinical furcation parameters (horizontal attachment levels [CAL-H], class of
      furcation invasion). Replicate measurements of CAL-H and furcation class were
      performed within 14 days in 420 molars of 105 patients with advanced
      periodontitis using a Nabers- (n=50), a TPS- (n=30) and a PCPUNC15-probe (n=25).
      Validity of clinical assessments was assessed by intrasurgical measurements. The
      standard deviation of single measurements (s) was calculated as a measure of the
      reproducibility of CAL-H measurements and weighted kappa-coefficients (Kw) to
      estimate the agreement of furcation class assessments. The s ranged from 0.55 to
      1.13 mm (Nabers), 0.55 to 1.02 mm (TPS), and 0.58 to 1.11 mm (PCPUNC15). For all
      probes, a statistically significantly smaller measurement error was observed in
      buccal and lingual sites than in mesiolingual and distolingual furcations (P <
      0.005). The Kw ranged from 0.59 to 0.89 (Nabers), 0.50 to 0.80 (TPS), and 0.53 to
      0.72 (PCPUNC 15). Multiple linear regression analysis identified distolingual
      location, probing depth (PD) and CAL-H as factors influencing the variability of
      CAL-H measurements. Whereas there was no statistically significant difference
      between pre- and intrasurgical CAL-H measurements using the Nabers probe, the TPS
      and PCPUNC15 probe underestimated CAL-H for distolingual furcations (P < 0.025).
      Using the Nabers probe, no asymmetries between pre- and intrasurgically obtained
      class of furcation involvement were revealed, while the TPS and PCPUNC15 probe
      underestimated furcation degrees (P < 0.1). Multiple linear regression analysis
      identified distolingual location and height of furcation, as well as PD, vertical
      attachment level (CAL-V) and type of probe, as factors influencing the validity
      of CAL-H measurements. Clinical diagnosis of furcation lesions using the 3 mm
      incrementally marked Nabers probe provides reproducible and valid information
      about furcation invasion.

PMID- 9579620
TI  - Root surface characteristics of primary teeth from children with prepubertal
      periodontitis.
AB  - This study describes the histologic characteristics of root surfaces of primary
      teeth from children with prepubertal periodontitis (PP). Fifteen primary teeth
      from 4 children with PP, and 2 control primary teeth from 2 healthy children were
      examined. Light microscopy revealed normal root surfaces in the control teeth. In
      contrast, the PP specimens revealed bacteria inside dentin tubules or covering
      cementum, a cuticle, or resorbed dentin; normal, wider than normal, or
      hypoplastic cementum; resorption lacunae with various depths; aplastic root
      resorption; alternate resorption and repair; and active repair. No cementoclasts
      were found in the resorption lacunae. Scanning electron microscopy revealed
      intrabony and suprabony root areas, and a "plaque free zone" (PFZ). Colonies of
      filaments were evident at the cemento-enamel junction (CEJ). The suprabony root
      surfaces had resorption lacunae, isolated short rods, calculus, colonies of
      filaments, or colonies composed by an heterogeneous bacterial population. The
      coronal boundary of the PFZ was the border of a sheet-like structure, which
      included isolated rods or filaments. At the PFZ, isolated filaments and rods, and
      a fibril matrix were evident. The apical boundary of the PFZ consisted of bundles
      of soft tissue remnants or the insertion of the periodontal fibers. The intrabony
      surfaces were mostly covered by soft tissue, which included isolated filaments
      and short rods. Resorption lacunae with or without soft tissue were also evident
      in this area. Crystals of calcium oxalate dihydrate and erythrocytes in distinct
      forms were found at various root areas. The present findings are different from
      those previously reported for hypophosphatasia specimens.

PMID- 9579621
TI  - Horizontal alveolar bone loss and vertical bone defects in an adult patient
      population.
AB  - The objectives of the present investigation were to analyze intraoral radiographs
      and to study 1) the distribution of the distance between the cemento-enamel
      junction (CEJ) and the alveolar bone level (BL) and 2) the prevalence and
      severity of vertical defects, and furcation lesions in 416 individuals seeking
      dental care. Full mouth radiographs were enlarged 7.5 times and the mesial and
      distal distances between CEJ and bone level were measured. The extent of
      interradicular molar radiolucencies was also measured. Images of 10,282 teeth
      were studied. Subjects were between 15 to 94 years (mean age: 47.2, S.D.+/-15.2).
      On average they had 24.8 teeth (S.D.+/-5.5). The mean distance CEJ-BL increased
      significantly up to age 45 (r2=0.07; beta=0.29; P < 0.0001) and remained stable
      thereafter r2=0.09, beta=-0.02, N.S.). The mean distance CEJ-bone level was 1.4
      mm (S.D.+/-0.7) in the 15 to 24 age group; 3.0 (S.D.+/-1.5) in the 45 to 54 age
      group; and 3.02 (S.D.+/-1.4) in the 75 to 94 age group. No vertical defects were
      found in 163 participants (39.3%); vertical defects > or = 3.0 mm were found in
      30.2% (126). Mesial defects were significantly more common that distal defects (P
      < 0.001). The extent of horizontal bone loss was correlated to extent of vertical
      defects (r2=0.88; P < 0.0001). The number of remaining teeth was not associated
      with horizontal or vertical bone loss. In conclusion, the study indicated that
      few of the individuals had extensive horizontal bone loss. Vertical defects
      suitable for guided tissue regeneration procedures however, were found in many
      patients.

PMID- 9579622
TI  - Evaluating the burst hypothesis at a site-specific level using the lack-of-fit
      test.
AB  - It has been hypothesized that periodontal disease progresses by means of sudden
      losses of periodontal attachment surface area. Obtaining reliable tests of this
      burst hypothesis has proven to be difficult; the signal (true model of disease
      progression) often gets lost in the noise. The purpose of this study was to
      determine how reliably we could distinguish sudden changes from linear disease
      progression at a site using a time series of clinical attachment levels.
      Specifically, the following question was investigated: If, in reality, disease
      progresses by means of sudden changes in clinical attachment level (bursts), and
      a linear model is fitted to these data, what is the likelihood of rejecting the
      linear model using the lack-of-fit test? This likelihood was determined as a
      function of the probing measurement error (range: 0.2 to 1.0 mm) and the number
      of clinical examinations over time. The results suggested that bursts of 2 mm or
      smaller cannot be reliably distinguished from linear disease progression using
      the lack-of-fit test, except under unusual clinical circumstances. Under typical
      clinical circumstances, burst sizes needed to be 3 to 5 mm in order to be
      reliably distinguished from linear disease progression. These results are
      probably overly optimistic. The ability to verify the burst hypothesis at the
      site level is likely to be even less than our results indicate because of various
      assumptions that were required. We conclude that the lack-of-fit test will
      reliably reject the linear model at a site-specific level only if true disease
      progresses in such a fashion that a handful of sudden changes leads to a tooth
      mortality event.

PMID- 9579623
TI  - Histology near periodontitis osteoclasts.
AB  - Histologic evaluation of periodontal tissues generally has included only areas
      adjacent to the gingival crevice, without knowledge or quantitation of alveolar
      crest osteoclastic (periodontitis) activity and infiltrate. The purpose of this
      study was to use human autopsy material to quantitate collagen and cell types
      adjacent to presumed periodontitis activity and quiescence, each in the same
      individual. Thirteen subjects contributed 4 sites each, 2 exhibiting alveolar
      crest periosteal osteoclasts in resorption lacunae/periodontitis activity (OC/PA)
      and 2 with no osteoclasts or resorption lacunae/ periodontal quiescence (NOC/PQ).
      Tissue and cell morphotypes were quantitated by 2 evaluators at 100 intersects in
      0.06 mm2 fields progressing from the alveolar crest toward the gingival crevice.
      Cell morphotypes/tissue components were compared between groups and fields using
      a general linear model with repeated measures. OC/PA fields adjacent to the
      alveolar crest contained significantly more intersects with macrophage-like cells
      (10.7+/-1.1 versus 5.3+/-0.6%, P=0.0003), lymphocytes (4.6+/-1.1 versus 0.7+/
      0.2%, P=0.0013), plasma cells (13.3+/-2.7 versus 2.1+/-0.6%, P=0.0004), and less
      with collagen (48.9+/-3.5 versus 75.0+/-2.0%, P=0.0001) than NOC/PQ fields.
      Numbers of lymphocytes and plasma cells increased (P=0.0006 and P=0.0002,
      respectively), and fibroblasts and collagen decreased (P=0.0024 and P=0.0001,
      respectively) in fields up to 1 mm closer to the gingival crevice. However,
      apparent osteoclastic activity in periodontitis subjects is associated with a
      significant inflammatory cell infiltrate, especially macrophages and plasma
      cells.

PMID- 9579624
TI  - Dynamics of serum immunoglobulin G avidity for Porphyromonas gingivalis in adult
      periodontitis.
AB  - The purpose of this study was to examine avidity of immunoglobulin G (IgG)
      antibody for surface antigens of Porphyromonas gingivalis in sera from patients
      with adult periodontitis. The antigens used were whole cell antigens,
      lipopolysaccharides (LPS), and fimbriae of non-invasive P. gingivalis ATCC 33277
      and invasive 16-1. Serum IgG titers for the P. gingivalis antigens were measured
      by enzyme-linked immunosorbent assay (ELISA) before and after periodontal initial
      preparation. IgG avidity was measured by diethylamine dissociation ELISA. IgG
      titers for the whole cell antigens of 16-1, LPS, and the fimbria antigens from
      both P. gingivalis strains were significantly higher in the patient group than
      those in the control group, whereas values for avidities were significantly lower
      in patient sera. Although we found a statistically significant decrease in the
      IgG titers of patients following initial preparation, avidities against the
      fimbria antigen of invasive 16-1 strain increased. The present study showed that
      IgG antibodies elicited in patients were different in their ability to respond to
      invasive P. gingivalis 16-1 and to non-invasive 33277. The patient sera with high
      IgG titers demonstrated low values for avidity, suggesting that IgG responses in
      patients play a limited role in colonization inhibition or elimination of P.
      gingivalis. The data indicate that periodontally healthy individuals may have
      highly functional antibodies which may protect against P. gingivalis
      colonization. Our findings suggest that the ability to produce functional
      antibodies in the patient group is lower than that in the periodontally healthy
      group, but the functional antibodies can be induced by the initial preparation.

PMID- 9579625
TI  - The effect of a 1-stage full-mouth disinfection on oral malodor and microbial
      colonization of the tongue in periodontitis. A pilot study.
AB  - Oral malodor affects a large proportion of the population and may be the cause of
      a significant social and psychological handicap. This pilot study aimed to
      examine whether a 1-stage full-mouth disinfection in periodontitis patients
      (scaling and root planing of all pockets within 24 hours together with the
      application of chlorhexidine to all intra-oral niches followed by chlorhexidine
      mouth rinsing for 2 months) resulted in a significant improvement in malodor when
      compared to a fractionated periodontal therapy (consecutive root planings per
      quadrant, at a 1 to 2 week interval). The baseline and outcome data concerning
      oral malodor were linked to the presence of tongue coating and to its roughness
      (fissures). Twenty-four patients with severe periodontitis were randomly
      allocated to test and control groups. At baseline and after 1 and 2 months, the
      concentration of volatile sulfur compounds (VSC) in the mouth was measured and
      organoleptic ratings (expired air and total mouth air) were given. Plaque samples
      were collected from the dorsum of the tongue to calculate the number of colony
      forming units (CFU) per ml (anaerobic culturing) as well as the number of
      pigmented CFU/ml. Both the baseline organoleptic ratings and the VSC scores
      correlated well with the presence of tongue coating but not with the tongue
      roughness. Because a correlation between tongue coating and its microbial load
      could not be detected, it was hypothesized that the tongue coating per se, and
      not the bacteria, might be responsible for the malodor. The 1-stage full-mouth
      disinfection resulted in a faster and additional reduction in the organoleptic
      ratings of the oral malodor, even after 2 months. This might be explained by the
      improved periodontal outcome and/or the more significant reduction in the CFU/ml
      of pigmented species. In contrast to the organoleptic ratings, which were
      significantly reduced in both treatment groups (when compared to baseline), the
      VSC levels remained unchanged. This pilot study indicates that a 1-stage full
      mouth disinfection has, in comparison to a standard periodontal therapy,
      additional beneficial effects in the treatment of oral malodor.

PMID- 9579626
TI  - Treatment of gingival recession with titanium reinforced barrier membranes versus
      connective tissue grafts.
AB  - It was the aim of this study to compare barrier membrane therapy with connective
      tissue grafts in the treatment of recession defects. Fifteen patients with 2
      paired vestibular recession defects participated in the study. After thorough
      scaling and root surface conditioning with tetracycline-HCl, defects were
      randomly assigned to 1 of 2 treatment modalities. In one of the defects, a
      trapezoidal mucoperiosteal flap was prepared, and a titanium reinforced expanded
      polytetrafluoroethylene membrane was adapted to the defect and secured by a sling
      suture. The membrane was subsequently covered by a coronally positioned flap
      secured with crown attached sutures. The other defect was treated with a
      connective tissue graft employing the "envelope technique." Twelve months after
      therapy, both treatment modalities showed significant root coverage and probing
      attachment gain. Gingival recession decreased from 3.6+/-0.7 mm to 0.5+/-0.5 mm
      for membrane treated defects and from 3.6+/-1.0 mm to 0.5+/-0.5 mm following use
      of grafts, corresponding to mean root coverages of 87.1% and 86.9%, respectively.
      Mean gains of keratinized tissue of 1.5 mm (membrane) and 2.5 mm (graft) could be
      observed. Thus, the results of this study demonstrate that both titanium
      reinforced barrier membranes and connective tissue grafts can be successfully
      used to treat periodontal recession defects.

PMID- 9579627
TI  - Cervical root resorption associated with guided tissue regeneration: a case
      report.
AB  - Root surface resorption, ankylosis (replacement resorption) and alveolar bone
      resorption are not uncommon sequelae to periodontal healing in both animal and
      human trials whether the treatment objective is regenerative, preventive, or
      conservative. The present report describes a case with progressive cervical root
      resorption in a patient who received periodontal regenerative treatment with
      guided tissue regeneration (GTR). A 46-year-old woman was referred for treatment
      of severe periodontitis. Remaining radiographic attachment was less than 50%.
      Following a period of 18 months, during which non-surgical and surgical therapies
      were performed, angular defects were diagnosed on radiographs and recurrent
      bleeding periodontal pockets (6 mm) were found in the proximal areas of 24 and
      25. Root caries was not present. Periodontal surgery with GTR was performed in
      this area. No immediate postsurgical complications were noted. Two years later,
      clinical and radiographic examinations revealed gingival recession with bleeding
      periodontal pockets (6 mm) which had partly uncovered severe proximal cervical
      resorptions in 25. Root surface caries was not present. Following surgical
      inspection, the root of 25 was removed. The root was subsequently prepared for
      histological analysis. Resorption cavities covered almost the entire cervical
      proximal surface of the root above intact infracrestal cementum and were covered
      by numerous CD68+, both mononuclear and multinucleated cells. In a central area
      as indicated on the radiographs, the cavities penetrated into the root canal.
      There was no evidence of root caries.

PMID- 9579628
TI  - Changes in peri-implant tissues subjected to orthodontic forces and ligature
      breakdown in monkeys.
AB  - The aims of this investigation were to histologically evaluate in monkeys the
      effect of a repetitive mechanical trauma alone on the peri-implant tissues, and
      the effect of a repetitive mechanical trauma in combination with ligature-induced
      peri-implantitis on the peri-implant tissues. The study used 5 male cynomolgus
      monkeys. Prior to the start of the study, all premolars and the first and second
      molars in the mandible were extracted. After a healing period of 12 weeks,
      following tooth extraction, split/full thickness flaps were elevated on both
      sides of the mandible in order to expose the bony ridge. Four implants, of 3.75
      mm in diameter and 7 mm in length, were then inserted on each side and the flaps
      were readapted and sutured in place. Following a healing period of 16 weeks, the
      second stage procedure was performed, impressions were taken, and custom-made
      crowns using a non-precious metal alloy were fabricated and inserted on all
      implants 4 weeks after abutment connection. At the same time peri-implantitis was
      induced on one side of the mandible by placing plaque-retentive ligatures around
      the implants. On the other side, an oral hygiene program consisting of thrice
      weekly brushing with a toothbrush and flour of pumice mixed with 2% chlorhexidine
      was initiated. Four months later, a repetitive mechanical trauma was initiated on
      implants 1 and 2 on both sides in the mandible. Consequently, a split mouth
      design was obtained: 1) test 1=ligature-induced peri-implantitis alone (LPNO); 2)
      test 2=ligature-induced peri-implantitits with a repetitive mechanical trauma
      (LPMT); 3) test 3=healthy peri-implant tissues with a repetitive mechanical
      trauma (MT); and 4) control (NO)=healthy peri-implant tissues with no repetitive
      mechanical trauma. Following 16 weeks of repetitive mechanical trauma the animals
      were sacrificed. Histologic observations and computed-assisted histometric and
      histomorphometric analyses were performed to determine the amount of peri-implant
      bone loss and the percentage of direct mineralized bone-to-implant contact around
      each endosseous oral implant. Histologically, all implants yielded
      osseointegration at the light microscopic level. There was a significant
      difference regarding the mean direct mineralized bone-to-implant contact length
      as a fraction of the total implant length between the healthy (i.e., MT and NO)
      and diseased sites (i.e., LPNO and LPMT) (P < 0.05). When comparing the percent
      of direct mineralized bone-to-implant contact for the 2 best threads of each
      implant and group, no significant difference (P=0.675) could be detected. Under
      the conditions of this study, the repetitive mechanical trauma showed no
      histologic effect on the peri-implant bone loss neither in healthy nor in
      diseased implant sites. The effects of excessive loading on osseointegration are
      presently not clearly understood. The key problem seems to be the determination
      when loading on implants exceeds the physiological range of bone adaptation which
      may then cause implant failure. Further research to elucidate this problem is
      essential.

PMID- 9579629
TI  - Guidelines for periodontal therapy. The American Academy of Periodontology.
AB  - The American Academy of Periodontology offers the following Guidelines for
      Periodontal Therapy. These guidelines are intended to fulfill the Academy's
      obligation to the public and to the dental profession to set forth the clinical
      objectives and scope of periodontal therapy. They also are designed to give
      guidance to state legislatures and agencies that regulate the practice of
      periodontology and should be considered in their entirety.

PMID- 9579630
TI  - Thrombin and antithrombotics.
AB  - From injury through healing, thrombin has several important functions in blood
      clotting, subsequent clot lysis, and tissue repair. These include edema,
      inflammation, cell recruitment, cellular releases, transformations, mitogenesis,
      and angiogenesis. Thrombin also participates in disease states, such as venous
      thrombosis, coronary thrombosis, stroke, and pulmonary emboli, among others and
      is implicated in atherosclerosis, the growth and metastasis of certain cancers,
      Alzheimer's disease, and perhaps other conditions. Thrombin must be continually
      generated to sustain normal and pathogenic processes. This is because of a
      variety of consumptive mechanisms. Unlike other activated factors in thrombotic
      and fibrinolytic pathways, and because thrombin promotes its own generation
      (feedback and cellular activation), thrombin is a primary target for
      therapeutics. Besides recombinant hirudins, Argatroban (Novastan) and Bivalirudin
      (Hirulog) are promising thrombin-directed inhibitors for antithrombotic
      intervention.

PMID- 9579631
TI  - Hemostasis and malignancy.
AB  - There is considerable evidence that the hemostatic system is involved in the
      growth and spread of malignant disease. There is an increased incidence of
      thromboembolic disease in patients with cancers and hemostatic abnormalities are
      extremely common in such patients. Antihemostatic agents have been successfully
      used to treat a variety of experimental tumors, and several clinical trials in
      humans have been initiated. Although metastasis is undoubtedly multifactorial,
      intravascular coagulation activation and peritumor fibrin deposition seem to be
      important. The mechanisms by which hemostatic activation facilitates the
      malignant process remain to be completely elucidated. Of central importance may
      be the presence on malignant cells of tissue factor and urokinase receptor.
      Recent studies have suggested that these proteins, and others, may be involved at
      several stages of metastasis, including the key event of neovascularization.
      Tissue factor, the principal initiator of coagulation, may have additional roles,
      outside of fibrin formation, that are central to the biology of some solid
      tumors.

PMID- 9579632
TI  - Laboratory investigation of hypercoagulability.
AB  - For many years, the laboratory investigation of patients with thrombophilia has
      lagged behind that of patients with bleeding diathesis. Improved understanding of
      the mechanisms that control and regulate coagulation, and the resultant
      recognition of new defects, have greatly stimulated clinical laboratory interest
      in this area. Assays to detect resistance to activated protein C; deficiencies of
      antithrombin, protein C, and protein S; and the presence of antiphospholipid
      antibodies are widely available and should form part of the investigation of
      patients that present with idiopathic thrombosis. Such a work-up will likely
      provide an explanation for thrombosis in 40 to 60% of patients. Abnormalities of
      fibrinogen and fibrinolysis may explain still more, although such defects are
      currently considered rare. In addition, presently unrecognized defects almost
      certainly exist, and the identification of such individuals will undoubtedly
      improve our understanding of the hemostatic mechanism. Laboratory tests to define
      the hypercoagulable state are continually being developed. They include whole
      blood coagulation and platelet function tests and novel activation markers.
      However, acceptance of these approaches by clinical laboratories has been slow.

PMID- 9579633
TI  - Pharmacological actions of sulodexide.
AB  - This report summarizes the results of some of the studies that have evaluated the
      pharmacokinetic, pharmacodynamic, anticoagulant, and antithrombotic properties of
      Sulodexide, which consists of a mixture of electrophoretically fast moving
      heparin (80% of the mass) and dermatan sulfate (the balance), with an average
      product (Mr) <8000. The low molecular weight (Mr) of the constituents of
      Sulodexide would predict that the product has the high bioavailability associated
      with low-Mr heparin and low-Mr dermatan sulfate. Given orally, subcutaneously, or
      by intravenous injection, Sulodexide exhibits antithrombotic and profibrinolytic
      properties in several animal models of venous and arterial thrombosis and has
      relatively high affinity for endothelial (and possibly other) cells.
      Additionally, in a large multicenter clinical trial involving 3986 patients who
      had recovered from acute myocardial infarction, oral Sulodexide was associated
      with a 32% reduction in death and a significant reduction of left ventricular
      thrombus formation. Compared with heparin, low-Mr heparin, and unfractionated and
      low-Mr dermatan sulfates, the doses of Sulodexide required for antithrombotic
      efficacy suggest that the combination of heparin and dermatan sulfate in
      Sulodexide provides a more effective antithrombotic mechanism than heparin/low-Mr
      heparins (which catalyze the antiprotease actions of antithrombin III) or
      dermatan sulfate/low-Mr dermatan sulfate (which catalyze thrombin inhibition by
      heparin cofactor II).

PMID- 9579634
TI  - Is coronary artery disease initiated perinatally?
AB  - Fetal origins of coronary disease were proposed recently on the basis of evidence
      that intrauterine growth retardation predisposed to precocious coronary disease.
      Recent ultrastructural studies suggest a pathogenesis supporting perinatal
      origins of coronary atherosclerosis. Half of infants show coronary intimal
      lesions with foam cells. Intimal proliferative lesions, precursive to lipid
      insudation of coronary arteries, have been reported in fetuses and newborns.
      Acute hypertension increases and promotes the progression of preexisting modified
      smooth muscle cell plaques in perinatal animals by developing prominent
      fibroplasia and collagenization. Such perinatal surges in blood pressure may be
      involved in the perinatal initiation of atherogenesis. Modification of naturally
      occurring lesions may depend on perinatal circumstances superimposed on the
      transition between fetal and adult patterns of circulation. Unusual perinatal
      stresses involving anoxia or catecholamine release in the mother, fetus, or
      newborn may predispose to the development of precocious coronary atherosclerosis
      later in life.

PMID- 9579635
TI  - The role of secondary growth factor production in thrombin-induced proliferation
      of vascular smooth muscle cells.
AB  - Alpha-thrombin is a multifunctional serine proteinase that is concentrated at
      sites of vascular injury and has been implicated in vascular healing responses
      following balloon injury. In addition to its well-known hemostatic effects,
      thrombin stimulates smooth muscle cell (SMC) proliferation via binding of
      protease activated receptor-1 (PAR-1), a seven transmembrane, G-protein-coupled
      cell surface receptor. Following activation of this receptor, SMC produce and
      secrete various autocrine growth factors, including platelet-derived growth
      factor-AA (PDGF-AA), basic fibroblast growth factor (bFGF), heparin binding
      epidermal growth factor (HBEGF), and transforming growth factor-beta (TGFbeta).
      The role that autocrine growth factors play in alpha-thrombin-induced
      proliferation will be discussed in this review.

PMID- 9579636
TI  - Transcellular signaling and pharmacological modulation of thrombin-induced
      production of plasminogen activator inhibitor-1 in vascular smooth muscle cells.
AB  - Thrombin formation is increased at the sites of vascular injury. Previous studies
      by our group and other groups indicated that the generation of plasminogen
      activator inhibitor-1 (PAI-1), the major physiological inhibitor for plasminogen
      activators, from cultured vascular smooth muscle cells (SMC) is elicited by
      thrombin. The present study demonstrates that the thrombin receptor, pertussis
      toxin-sensitive G protein, genistein-sensitive tyrosine kinase, phospholipase C,
      and protein kinase C may be involved in thrombin-induced PAI-1 production in
      cultured baboon aortic SMC. Forskolin and 8-bromo-cyclic AMP inhibited thrombin
      induced PAI-1 production in cultured SMC. Treatment with hirulog-1, a synthetic
      thrombin receptor inhibitor, suppressed thrombin-induced PAI-1 generation at mRNA
      and protein levels in SMC. The results of the present study suggest that
      transmembrane receptor and multiple signal transduction systems are involved in
      thrombin-induced increase in PAI-1 transcription in vascular SMC. The production
      of PAI-1 stimulated by thrombin in vascular SMC may be pharmacologically
      modulated by thrombin receptor inhibitor.

PMID- 9579637
TI  - Research and development commitments in an integrated plasma collection and
      plasma fractionation environment.
AB  - Plasma fractionation has emerged as one of the most scientifically demanding
      fields in the biopharmaceutical area. Producing safe plasma derivatives implies
      the development, use, and proper understanding of sensitive testing technologies
      to detect infection markers in starting plasma. It also requires the
      implementation of carefully selected, nondenaturing, efficient plasma protein
      purification and viral reduction technologies that do not alter the physiological
      functions and clinical potential of plasma proteins. Success in this field can be
      achieved only by a strong commitment to sustain constant research and development
      of projects targeting the production of safer and innovative plasma products.

PMID- 9579638
TI  - Use of the electron microscope for diagnosis of platelet disorders.
AB  - The electron microscope is generally regarded as a sophisticated instrument used
      almost exclusively for basic research. However, ultrastructural methods can be
      just as valuable for the clinical diagnosis of inherited platelet disorders, as
      for more fundamental studies. This report describes several instances in which
      electron microscopy has been critical for identifying and characterizing genetic
      problems. For example, platelet storage pool deficiency (SPD) is due to a marked
      decrease or absence of the organelles storing adenine nucleotides, serotonin, and
      calcium destined for secretion during the platelet release reaction. The
      organelles are referred to as dense bodies because they are inherently electron
      opaque. As a result, platelet SPD is more rapidly and reliably diagnosed in the
      electron microscope than by any other technique. Giant platelet disorders have
      presented a bewildering array. The electron microscope has made it possible to
      separate the various types into distinct conditions based on the nature of
      platelet structural defects and inclusions found in leukocytes. Immunogold and
      cytochemical techniques have expanded the horizon of electron microscopy in the
      evaluation of platelet disorders and have assured its continued use for this
      purpose in the future.

PMID- 9579639
TI  - Fibrinogen structure and fibrin clot assembly.
AB  - Fibrinogen is a complex multifunctional protein, which contains constitutive
      association sites (gammaXL, D:D, Da, Db) as well as cryptic sites that become
      exposed as a result of fibrinogen proteolysis by thrombin (EA, EB). Utilization
      of these sites by self-association (gammaXL or D:D) or by association with
      exposed complementary fibrin sites (Da:EA, Db:EB) produces an orderly process of
      molecular assembly to form linear and branched fibrils, concomitant with lateral
      fibril associations and factor XIIIa-mediated fibrin crosslinking that together
      result in the mature fibrin network.

PMID- 9579640
TI  - Comparative in vitro investigation of prothrombin complex concentrates.
AB  - Three commercial prothrombin complex concentrates (PCC) were compared in vitro.
      Differences in the activities or contents, respectively, of the PCC factors FII,
      FVII, FIX, FX and the proteins C, S, and Z (antigen) in particular were found.
      Global tests of activated factors did not reveal marked differences between the
      products. Neither free thrombin nor elevated levels of activated FX were
      detected. In contrast, analyses of FVIIa, of residual amidolytic activities, and
      of concentrations of unwanted ingredients demonstrated considerable differences
      between the products. While antithrombin III was detected only in two of three
      concentrates, heparin was found in all PCCs but in markedly different
      concentrations. Although the homogeneity of the products has been clearly
      improved in comparison with former comparative investigations, the products can
      be distinguished by their compound profile and by a couple of in vitro assays.

PMID- 9579641
TI  - Therapeutic use of antithrombin concentrate in sepsis.
AB  - Sepsis and its associated complications of disseminated intravascular coagulation
      (DIC) and multiple organ dysfunction syndrome (MODS) continue to be a major cause
      of morbidity and mortality. Improved detection of all forms of DIC is essential
      to assure earlier diagnosis. Studies already indicate that the therapeutic use of
      antithrombin (AT) concentrate may produce a more positive outcome for sepsis
      associated DIC. If DIC could be identified earlier and AT concentrate could then
      be given earlier in the sepsis continuum, study results for the use of AT
      concentrate in humans might reveal a statistically significant difference versus
      placebo, and the efficacy of AT concentrate for this syndrome is more likely to
      be proved. Fixed-bolus doses of AT concentrate based on body weight are currently
      preferred, but improved, user-friendly assays for plasma AT levels would permit
      more rapid turnaround time for AT results and could help fine-tune the use of AT
      concentrate to the specific needs of each patient. Clinical trials involving the
      therapeutic use of AT concentrate in sepsis should continue, and it can be hoped
      that their design will reflect the concepts and conclusions offered by this panel
      of investigators.

PMID- 9579643
TI  - How simple is the organization of the olfactory glomerulus?: the heterogeneity of
      so-called periglomerular cells.
AB  - Recent progress in the studies of the olfactory system, especially in the
      molecular biological studies, makes it one of the useful sensory model systems
      for understanding neural mechanisms for the information processing. In the
      olfactory bulb, the primary center of the olfactory system, glomeruli are
      regarded as important functional units in the transmission of odorant signals and
      in processing the olfactory information, but have been believed to be composed by
      only a small number of neuronal types and thus to be simple in their neuronal and
      synaptic organization. However, accumulating morphological data reveal that each
      type of neurons might further consist of several different subpopulations,
      indicating that the organization of glomeruli might not be so simple as it was
      believed. Here we describe an aspect of the structural organization of glomeruli,
      focusing on the heterogeneities of periglomerular neurons in mammalian main
      olfactory bulb.

PMID- 9579644
TI  - Vagal afferent projections to lobule VIIa of the rabbit cerebellar vermis related
      to cardiovascular control.
AB  - In decerebrate rabbits we recorded simultaneously field potentials in lobule VIIa
      of the vermal cerebellar cortex and the vagal compound action potentials (vCAPs)
      proximally in the vagus nerve following electrical stimulation distally in the
      same nerve at different intensities. Four principal components of the vCAP were
      distinguished based on their peak conduction velocities. Their velocities were
      component I, 67-100 m/s; II, 28-50 m/s; III, 6-28 m/s, IV, 0.4-1.3 m/s. A
      collision test based on stimulating the recurrent laryngeal nerve identified
      component I and sub-component IIa of the vCAP as being due to the motor fibres of
      the descending limb of the nerve. The field potentials evoked in lobule VIIa by
      electrical stimulation of the cervical vagus nerve were climbing fibre responses
      as judged by the characteristics of their lamina profile and their response to
      high frequency stimulation. These field potentials in lobule VIIa correlated most
      closely with the component III of the vCAP; particularly with a sub-component
      IIIa of the vagus. Based on the investigations by Evans and Murray (1954)
      (Histological and functional studies on the fibre composition of the vagus nerve
      of the rabbit. J. Anat. (Lond.) 88, 320-337) in the rabbit, and by Paintal (1963)
      (Vagal afferent fibres. Ergeb. Physiol. 52, 74-156) and Mei (1970)
      (Cardiovascular and respiratory vagal mechanoreceptors in the cat. Exp. Brain
      Res. 11, 480-501) in the cat, component III is most likely to be due to receptors
      from the heart and a part of the pulmonary stretch receptors.

PMID- 9579642
TI  - PFA-100 system: a new method for assessment of platelet dysfunction.
AB  - The PFA-100 system is a platelet function analyzer designed to measure platelet
      related primary hemostasis. The instrument uses two disposable cartridges: a
      collagen/epinephrine (CEPI) and a collagen/ADP (CADP) cartridge. Previous
      experience has shown that CEPI cartridges detect qualitative platelet defects,
      including acetylsalicylic acid (ASA)-induced abnormalities, while CADP cartridges
      detect only thrombocytopathies and not ASA use. In this seven-center trial, 206
      healthy subjects and 176 persons with various platelet-related defects, including
      127 ASA users, were studied. The platelet function status was determined by a
      platelet function test panel. Comparisons were made as to how well the defects
      were identified by the PFA-100 system and by platelet aggregometry. The reference
      intervals for both cartridges, testing the 206 healthy subjects, were similar to
      values described in smaller studies in the literature [mean closure time (CT) 132
      s for CEPI and 93 s for CADP]. The use of different lot numbers of cartridges or
      duplicate versus singleton testing revealed no differences. Compared with the
      platelet function status, the PFA-100 system had a clinical sensitivity of 94.9%
      and a specificity of 88.8%. For aggregometry, a sensitivity of 94.3% and a
      specificity of 88.3% were obtained. These values are based on all 382 specimens.
      A separate analysis of sensitivity by type of platelet defect, ASA use versus
      congenital thrombocytopathies, revealed for the PFA-100 system a 94.5%
      sensitivity in identifying ASA users and a 95.9% sensitivity in identifying the
      other defects. For aggregometry, the values were 100% for ASA users and 79.6% for
      congenital defects. Analysis of concordance between the PFA-100 system and
      aggregometry revealed no difference in clinical sensitivity and specificity
      between the systems (p > 0.9999). The overall agreement was 87.5%, with a Kappa
      index of 0.751. The two tests are thus equivalent in their ability to identify
      normal and abnormal platelet defects. Testing 126 subjects who took 325 mg ASA
      revealed that the PFA-100 system (CEPI) was able to detect 71.7% of ASA-induced
      defects with a positive predictive value of 97.8%. The overall clinical accuracy
      of the system, calculated from the area under the ROC curve, was 0.977. The data
      suggest that the PFA-100 system is highly accurate in discriminating normal from
      abnormal platelet function. The ease of operation of the instrument makes it a
      useful tool to use in screening patients for platelet-related hemostasis defects.

PMID- 9579645
TI  - Distribution and development of NMDA receptor activities at hippocampal synapses
      examined using mice lacking the epsilon1 subunit gene.
AB  - The effects of targeted disruption of the gene encoding N-methyl-D-aspartate
      (NMDA) receptor epsilon1 subunit were examined in hippocampal CA1 pyramidal cell
      synapses and compared with the effects in the CA3 region. The mutation resulted
      in the significant reduction of NMDA receptor activities at the synapses in the
      CA1 stratum oriens, as had been observed in the CA1 stratum radiatum which we
      reported before. This result was in sharp contrast to our previous observation
      that in the CA3 region, the epsilon1 mutation suppressed NMDA receptors at the
      synapses in the stratum radiatum but not in the stratum oriens. It is suggested
      that the subunit composition of NMDA receptors may not be determined simply by
      the location within a pyramidal cell, but by other factors such as properties of
      synaptic inputs. We also examined the postnatal development of long-term
      potentiation (LTP) in the CA3 region. The development of LTP at the CA3 stratum
      radiatum synapses closely followed the development of the epsilon1 subunit, and
      the epsilon1 mutation strongly suppressed this LTP, suggesting that the targeted
      disruption of the epsilon1 subunit may not be compensated by other epsilon
      subunits. The LTP at the CA3 stratum oriens synapses was not significantly
      affected by the mutation at any age.

PMID- 9579646
TI  - Differential effects of two motor tasks on ERPs in an auditory classification
      task: evidence of shared cognitive resources.
AB  - The aim of the study was to assess cognitive demands and fatigue during the
      execution of two different motor tasks. Event-related brain potentials (ERPs)
      were recorded from 15 healthy subjects while they concurrently performed, (1) one
      of two motor tasks, and (2) a three stimulus (70% standard tones, 15% target
      tones, 15% novel stimuli) auditory classification task. Both motor tasks required
      the externally paced adduction of the right thumb with the force task requiring a
      precise movement (feedback given) with about 50% of maximum force output (6 s on
      task, 4 s rest) while the displacement task required the same precise movement
      with only minimal force requirements. In separate sessions, both tasks were
      performed for about an hour with the subjects concurrently paying attention to
      the auditory task with button presses required for the target stimuli. This
      provided a dual task situation with trade-offs in P3b amplitude as a function of
      difficulty of the primary (motor) task. The P3b to the auditory target stimuli
      was reduced during the force session compared to the displacement session,
      indicating that the force-task placed a higher demand on cognitive resources. No
      differential effect of fatigue (time on task) could be ascertained over six
      consecutive parts of the session. The P3a component, a putative correlate of
      orienting of attention, showed a rapid attenuation over time but, attesting to
      its automatic nature, no effect of concurrent motor task. ERP components recorded
      timelocked to the movements showed a marked difference between the two tasks with
      the displacement task giving rise to higher amplitudes. Moreover, only for the
      force task an influence of time on task (fatigue) on the MP was found. The dual
      task methodology is a potentially useful tool to disentangle cognitive and motor
      components of central fatigue.

PMID- 9579647
TI  - Effects of prenatal methylazoxymethanol treatment on striatal dopaminergic
      systems in rat brain.
AB  - To further examine the effects of prenatal methylazoxymethanol (MAM) treatment on
      striatal dopaminergic systems, the status of presynaptic dopamine transporters
      was examined by quantitative autoradiography of [3H]GBR 12935 binding.
      Significantly higher [3H]GBR 12935 binding was seen in MAM-lesioned striatum in
      comparison to the controls, indicating relative dopaminergic hyperinnervation in
      MAM-induced hypoplastic striatum. The effect of prenatal MAM treatment on
      extracellular levels of dopamine and its metabolites in the striatum was also
      examined using in vivo microdialysis. As measured in conscious freely-moving
      rats, prenatal MAM treatment significantly increased basal dopamine (DA) and 3,4
      dihydroxyphenylacetic acid (DOPAC) release in the striatum in comparison with
      control rats. These data suggest that in accordance with morphological
      dopaminergic hyperinnervation, dopaminergic functions are significantly augmented
      in MAM-lesioned brains. Thus, it is suggested that MAM-induced microencephalic
      rats should serve as a good animal model for the study of augmented dopaminergic
      functions in the striatum.

PMID- 9579648
TI  - Induction of Fos-like immunoreactivity in the hypothalamic, medullary and
      thoracic spinal cord neurons following middle cerebral artery occlusion in rats.
AB  - This study is a sequel of our previous work which demonstrated the expression of
      Fos-like immunoreactivity (Fos-LI) in the spinal cord motoneurons of rat
      following permanent occlusion of the middle cerebral artery (MCA). We report here
      Fos-LI in the hypothalamic, medullary and thoracic spinal cord neurons some of
      them are believed to be involved in cardiovascular regulation after the cerebral
      ischaemic insult. At 1 and 2 h, especially in the latter after right sided MCA
      occlusion, Fos-LI confined to the cell nucleus, was detected bilaterally in cells
      of the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of the
      hypothalamus, the nucleus of the solitary tract (NTS), the area postrema and
      ventrolateral medulla (VLM). A few Fos-like immunoreactive neurons were observed
      in the nucleus raphe pallidus and obscurus, and in the intermediolateral nucleus
      of the thoracic spinal cord. In the corresponding areas in sham-operated animals,
      Fos-like immunoreactive neurons were sparsely distributed or absent.
      Colocalization study showed that a variable number of the Fos-like immunoreactive
      neurons in NTS and VLM coexpressed tyrosine-hydroxylase (TH) immunoreactivity.
      Such double labelled neurons appeared to be more common in the latter. It is
      suggested that the induction of Fos-LI in neurons of the hypothalamus, medulla
      and thoracic spinal cord was linked to cardiovascular regulation following the
      middle cerebral artery occlusion.

PMID- 9579649
TI  - Calcium-binding proteins in primate cerebellum.
AB  - Single and double antigen localization procedures were used to study the
      distribution of the calcium-binding proteins calretinin, calbindin and
      parvalbumin in the cerebellum of the squirrel monkey (Saimiri sciureus). The
      immunostaining experiments have revealed that each of the three calcium-binding
      proteins occurred, either alone or in various combinations, in many neuronal
      types of the monkey cerebellum, including the Purkinje cells. Immunoreactivity
      for calbindin was detected in virtually all Purkinje cells, whereas
      immunoreactivity for calretinin and parvalbumin was encountered only in some
      subpopulations of Purkinje cells. In the vermal region, parvalbumin
      immunostaining appeared in the form of typical weak and strong alternating
      parasagittal bands. Calretinin immunoreactivity was found in virtually all
      neurons and fiber systems related to the granular layer, including the
      monodendritic cells, the granule cells and their parallel fibers, the Golgi and
      Lugaro cells and the mossy fibers. The Golgi cells also displayed calbindin and
      parvalbumin immunoreactivity. Parvalbumin was found to labeled both the climbing
      and mossy fibers, as well as the basket and stellate cells lying in the molecular
      layer. These results reveal that virtually all the different neuronal types in
      the primate cerebellum contain at least one of three calcium-binding proteins
      investigated in the present study. Furthermore, calretinin appears to be a
      particularly reliable molecular maker for all the neuronal elements associated
      with the granular layer in the primate cerebellum.

PMID- 9579650
TI  - Neuronal connections between the auricular skin and the sympathetic pre- and
      postganglionic neurons of the dog as studied by using pseudorabies virus.
AB  - Pseudorabies virus (PrV) as a neuronal tracer was microinjected into the concave
      surface of the puppy's left pinna to establish the morphological basis of somato
      visceral linkage. The virus infected neurons were detected by FITC conjugated
      with polyclonal swine anti-PrV serum. Labelled neurons were localized in: (1) the
      trigeminal, geniculate and superior vagal ganglia; (2) the subnucleus caudalis of
      the spinal trigeminal nucleus; (3) the intermediolateral column (IML) of the
      thoracolumbar segments and (4) the sympathetic chain ganglia. Present results
      suggest that when injected into the peripheral nerves, PrV was retrogradely
      transported to the nerve cell bodies located in the respective sensory ganglia.
      From the first order sensory neurons, the virus would self-replicate and was
      transported trans-synaptically via the brainstem nuclei and IML to reach the
      neurons in the sympathetic ganglia.

PMID- 9579651
TI  - The information transmitted by ensembles of primary spindle afferents is
      diminished when ketamine is used as a pre-anaesthetic.
AB  - The effect of pre-anaesthetic ketamine on ensemble coding of different stimuli
      consisting of muscle stretches of various amplitudes was studied for ensembles of
      simultaneously recorded primary muscle spindle afferents (MSAs). The experiments
      were conducted on 8 alpha-chloralose anaesthetised cats. Three of the cats
      received a pre-anaesthetic dose of ketamine (25 mg/kg) injected subcutaneously
      (ketamine group), while the remaining five animals did not (non-ketamine group).
      Data for ensemble coding were collected both before and after cutting the ventral
      root. A method based on principal component analysis and algorithms was used to
      quantify stimulus discrimination and an ANOVA tested differences between groups
      as well as differences due to ventral root cutting. When the fusimotor supply was
      intact, a general trend of an increase in the ability to discriminate stimuli
      with increasing ensemble size was observed for both groups, however, this trend
      was significantly greater for the non-ketamine group as compared to the ketamine
      group. When the ventral root was cut, the discrimination pattern for the non
      ketamine group decreased significantly (as compared to before ventral root
      cutting), however, no change occurred for the ketamine group. Consequently, no
      difference in discrimination pattern was detected between groups after ventral
      root cutting. The reduction in information transmitted by ensembles of primary
      MSAs when ketamine is used as a pre-anaesthetic may suggest that ketamine elicits
      an adverse affect on the fusimotor system.

PMID- 9579652
TI  - Effects of repeated cyclosporin A administration on iminodipropionitrile-induced
      dyskinesia and TRE-/CRE-binding activities in rat brain.
AB  - To clarify the involvement of immunophilin ligands in the pathogenesis and
      pathophysiology of dyskinesia, we examined the effects of repeated administration
      of cyclosporin A (CsA) on rat dyskinesia induced by repeated injection of
      iminodipropionitrile (IDPN 100 mg/kg, i.p., for 7 days). The addition of CsA
      treatment (5 mg/kg, s.c., 1 h before each IDPN injection) exacerbated IDPN
      induced dyskinesia. In the group treated with both CsA and IDPN, the
      concentration of dopamine was significantly increased in the striatum and nucleus
      accumbens compared with the group treated with IDPN alone. Furthermore, in the
      electrophoretic mobility shift assay, the injection of CsA + IDPN increased
      binding activities of transcription factors to the TPA (12-O-tetradecanoylphorbol
      13-acetate)-responsive element (TRE) and to the cAMP response element (CRE) in
      the striatum and nucleus accumbens, compared with those in rats treated with IDPN
      alone. The levels of D1-receptor mRNA in the striatum were significantly
      decreased in the IDPN-treated rats but were at the control level in the rats
      given CsA + IDPN. These findings suggest that the behavioral aggravation of the
      IDPN-induced dyskinesia caused by CsA administration may be due to the
      acceleration of the pre- and post-synaptic dopaminegic systems via activation of
      transcription factors which bind upstream to tyrosine hydroxylase and D1-receptor
      genes, and that the immunophilin binding agents such as CsA are involved in this
      aggravated dyskinesia.

PMID- 9579653
TI  - A novel metabolic communication between neurons and astrocytes: non-essential
      amino acid L-serine released from astrocytes is essential for developing
      hippocampal neurons.
AB  - A hippocampal astrocyte conditioned medium (HACM) supported the survival of
      hippocampal neurons under a serum-, glia-free culture setting. The neurotrophic
      activity in HACM was mostly recovered in low molecular weight fractions (Mr <
      3000), which contained high levels of L-serine and L-alanine. However, L-serine
      alone significantly improved the neuronal survival and neurite growth in a stereo
      specific manner. Other non-essential amino acids had no effect. These results
      strongly suggest that L-serine, released by astrocytes, is essential for the
      survival and phenotypic growth of hippocampal neurons.

PMID- 9579654
TI  - Recognition of analogous and homologous protein folds--assessment of prediction
      success and associated alignment accuracy using empirical substitution matrices.
AB  - Fold recognition methods aim to use the information in the known protein
      structures (the targets) to identify that the sequence of a protein of unknown
      structure (the probe) will adopt a known fold. This paper highlights that the
      structural similarities sought by these methods can be divided into two types:
      remote homologues and analogues. Homologues are the result of divergent evolution
      and often share a common function. We define remote homologues as those that are
      not easily detectable by sequence comparison methods alone. Analogues do not have
      a common ancestor and generally do not have a common function. Several sets of
      empirical matrices for residue substitution, secondary structure conservation and
      residue accessibility conservation have previously been derived from aligned
      pairs of remote homologues and analogues (Russell et al., J. Mol. Biol., 1997,
      269, 423-439). Here a method for fold recognition, FOLDFIT, is introduced that
      uses these matrices to match the sequences, secondary structures and residue
      accessibilities of the probe and target. The approach is evaluated on distinct
      datasets of analogous and remotely homologous folds. The accuracy of FOLDFIT with
      the different matrices on the two datasets is contrasted to results from another
      fold recognition method (THREADER) and to searches using mutation matrices in the
      absence of any structural information. FOLDFIT identifies at top rank 12 out of
      18 remotely homologous folds and five out of nine analogous folds. The average
      alignment accuracies for residue and secondary structure equivalencing are much
      higher for homologous folds (residue approximately 42%, secondary structure
      approximately 78%) than for analogues folds (approximately 12%, approximately
      47%). Sequence searches alone can be successful for several homologues in the
      testing sets but nearly always fail for the analogues. These results suggest that
      the recognition of analogous and remotely homologous folds should be assessed
      separately. This study has implications for the development and comparative
      evaluation of fold recognition algorithms.

PMID- 9579655
TI  - Prediction of protein hydration sites from sequence by modular neural networks.
AB  - The hydration properties of a protein are important determinants of its structure
      and function. Here, modular neural networks are employed to predict ordered
      hydration sites using protein sequence information. First, secondary structure
      and solvent accessibility are predicted from sequence with two separate neural
      networks. These predictions are used as input together with protein sequences for
      networks predicting hydration of residues, backbone atoms and sidechains. These
      networks are trained with protein crystal structures. The prediction of hydration
      is improved by adding information on secondary structure and solvent
      accessibility and, using actual values of these properties, residue hydration can
      be predicted to 77% accuracy with a Matthews coefficient of 0.43. However,
      predicted property data with an accuracy of 60-70% result in less than half the
      improvement in predictive performance observed using the actual values. The
      inclusion of property information allows a smaller sequence window to be used in
      the networks to predict hydration. It has a greater impact on the accuracy of
      hydration site prediction for backbone atoms than for sidechains and for non
      polar than polar residues. The networks provide insight into the mutual
      interdependencies between the location of ordered water sites and the structural
      and chemical characteristics of the protein residues.

PMID- 9579656
TI  - Quantitative structure-function and structure-stability relationships of
      purposely modified proteins.
AB  - Quantitative structure-function relationships (QSFR) and quantitative structure
      stability relationships (QSSR) analyses are described here. The objective of
      these analyses is to investigate and quantitatively describe the effect of the
      changes in structure of protein on its function or stability. During the
      analysis, the structural and physico-chemical properties of the amino acid
      residues are related to activity or stability data derived for the group of
      proteins containing systematic substitutions at certain positions. Four examples
      of the application of these analyses on the data obtained with proteins modified
      by site-directed mutagenesis experiments are provided. Structure-function
      relationships were studied for 15 mutants in position 172 of the haloalkane
      dehalogenase and 19 mutants in position 222 of the subtilisin, while the
      structure-stability relationships were investigated for 13 mutants in position
      157 of phage T4 lysozyme and 18 mutants in position 49 of alpha-subunits
      tryptophan synthase. A total of 402 molecular descriptors derived from AAindex
      database were used to quantify amino acid properties and the multivariate
      statistical technique--partial least squares projections to latent structures-
      was used to identify those of them which are important for explanation of the
      activity and stability data. Quantitative models were developed and internally
      validated for every data set. The possibilities for further development of both
      analyses and their application for predictive and analytical purposes in protein
      engineering research are discussed.

PMID- 9579657
TI  - Comparison of the 3D models of four different human IL-7 isoforms with human and
      murine IL-7.
AB  - The three-dimensional (3D) models of several alternatively spliced isoforms (ISO1
      through ISO4) of human interleukin-7 (hIL-7) are presented. They are based on
      sequences of mRNA recently discovered in follicular dendritic cells (FDC) and
      primary cultures of endothelial cells or smooth muscle cells. The structures were
      docked to a previous model of the human IL-7 receptor, containing the IL-7
      specific (IL-7R) and common gamma (gamma(c)) chain. Two different models of
      murine IL-7 (mIL-7) were generated as well and docked to this receptor. For an
      evaluation of the structures and the possible biological role of the isoforms,
      the models were analysed in detail and a series of enthalpy calculations was
      carried out. Compared with hIL-7, ISO1 appears to bind equally well to hIL-7R,
      but even better to the gamma(c) chain. This suggests an agonist role of ISO1,
      which has already been shown experimentally. The prediction that ISO2 exhibits
      reduced affinity to hIL-7R is supported by experiments where it had been shown to
      be inactive in a human test system. However, ISO2 as well as ISO3 could represent
      antagonists for hIL-7. Remarkably, mIL-7 appears to bind significantly less well
      to hIL-7R, which is in line with experimental observations that it is not active
      in the human system. The sequences of the isoforms support the helix assignment
      made for the previous hIL-7 model.

PMID- 9579658
TI  - Cysteine contributions to metal binding preference for Zn/Cd in the beta-domain
      of metallothionein.
AB  - Previous studies showed that metals in the beta-domain of metallothionein (MT)
      are more readily exchangeable and the level of avidity is site specific. This is
      reflected by energy differences computed with a series of simulated structures
      derived from X-ray crystallography. In this study, we examined further the
      contribution of each of the nine cysteines in the beta-domain. By semi-empirical
      MNDO calculations, we observed that the relative average binding strength is the
      strongest for Cys21 to Cd[M4] and for Cys26 to Zn[M3], except for the bridging
      cysteines. These results suggest that binding site preference for Zn/Cd is
      determined by binding strength between specific cysteines and metal ion species.

PMID- 9579659
TI  - Designing the hydrophobic core of Thermus flavus malate dehydrogenase based on
      side-chain packing.
AB  - We have developed a computational method for the de novo design of hydrophobic
      cores of proteins and tested it experimentally. The method is composed of a pair
      of programs, (i) to optimize side-chain conformations using an updated rotamer
      library for potential hydrophobic residues, based on the backbone structure of
      the protein of interest, and (ii) to estimate changes in Gibbs free energies
      between the folded and unfolded structures of the optimized sequence. Using these
      programs, we have engineered several variants of Thermus flavus malate
      dehydrogenase. To quantitate the stability change in each variant, the circular
      dichroism spectra of the proteins were measured as a function of guanidine
      hydrochloride concentration and deltadeltaG(H2O) values of the proteins were
      determined by extrapolation of the experimental data. However, variants with
      double replacements showed different denaturation cooperativity from that of the
      wild type and therefore it was difficult to simply compare the theoretical and
      experimental stability of each variant using calculated deltadeltaG and
      experimental deltadeltaG(H2O) values. When the calculated deltadeltaG values were
      compared with those at 3.5 M guanidine hydrochloride, which was the transition
      midpoint obtained from the denaturation curve of the wild type, good correlation
      was observed.

PMID- 9579660
TI  - A mutant D-amino acid aminotransferase with broad substrate specificity:
      construction by replacement of the interdomain loop Pro119-Arg120-Pro121 by Gly
      Gly-Gly.
AB  - D-amino acid aminotransferase (EC 2.6.1.21) catalyzes the interconversion of
      various D-amino acids and 2-oxo acids. Each homodimer subunit consists of two
      domains, which are connected by a single loop, Asn118-Pro119-Arg120-Pro121. The
      loop has no direct contact with the active site region or the cofactor, pyridoxal
      5'-phosphate. We attempted to increase the conformational flexibility of this
      loop through a triple glycine substitution. The resultant mutant P119G-R120G
      P121G has features clearly different from the wild-type enzyme under overall as
      well as half-reaction conditions. The pre-steady-state kinetic analyses of half
      reactions showed that the mutant enzyme has kmax values higher than the wild-type
      enzyme towards most D-amino acids examined. A concomitant decrease in substrate
      affinity (1/Kd), particularly for acidic amino acids, was also observed. A
      putative binding site for the distal carboxyl group of acidic amino acids in the
      wild-type enzyme was incidentally displaced by the loop mutation, indicating a
      functional linkage between the interdomain loop and the active site region. This
      study has exemplified the usefulness of engineering relatively distant loops as a
      means to modify substrate specificity of an enzyme.

PMID- 9579661
TI  - Identification of four amino acid residues essential for catalysis in human
      cytidine deaminase by site-directed mutagenesis and chemical modifications.
AB  - By site-directed mutagenesis on human cytidine deaminase (CDA), five mutant
      proteins were obtained: C65A, C99A, C102A, E67D and E67Q. The three cysteine
      mutants were completely inactive, whereas E67D and E67Q showed a specific
      activity about 200- and 200000-fold lower, respectively, than the wild-type CDA.
      Zinc analysis revealed that only E67D, E67Q and C65A contained 1 mol Zn2+/mol
      subunit as in the wild-type CDA. Kinetic measurements with the specific
      carboxylic group reagent N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline
      performed on wild-type CDA suggest that Glu67 is essential for the catalytic
      process. Furthermore, when both native and denatured CDA was titrated with 5,5'
      dithiobis(2-nitrobenzoic acid) six sulfhydryl groups were detected, whereas in
      the denatured and reduced enzyme nine such groups were found, according to the
      sequence data. When p-hydroxymercuriphenyl sulfonate was used, nine sulfhydryl
      groups were detectable and the release of 1 mol of zinc per mole of CDA subunit
      was revealed by the metal indicator dye 4-(2-pyridylazo)resorcinol. It seems
      plausible that the limiting step for the maintenance of zinc in the active site
      is the formation of coordination between Cys99 and Cys102, whereas Cys65 could
      lead the zinc to the correct position and orientation within the active site.

PMID- 9579662
TI  - Effects of substitutions in the binding surface of an antibody on antigen
      affinity.
AB  - The interactions between the Fab and single-chain Fv (scFv) fragments of an
      antibody (NC10) and its antigen, influenza virus neuraminidase, were analysed in
      the crystal structures of the Fab-neuraminidase and scFv-neuraminidase complexes.
      To investigate the contribution to binding made by cavities, salt links and
      hydrogen bonds in the antibody-antigen interface, 14 single amino acid
      replacements were made at six contact residues in the scFv fragment by site
      directed mutagenesis. The binding affinity of each mutant scFv antibody for
      neuraminidase was determined with a BIAcore optical biosensor. Four of the
      mutations resulted in large changes in the free energy of binding to
      neuraminidase (deltadeltaG > 1 kcal/mol) and together may account for
      approximately 70% of the free energy of binding. Hence these data support the
      theory that a small number of residues form the 'functional epitope' and are most
      important for binding of NC10 to neuraminidase. The salt link between antibody
      residue (Asp)H56 and (Lys)N432 from neuraminidase was demonstrated to be
      important for affinity, since substitution of (Asp)H56 with Asn caused a large
      reduction in the free energy of binding (deltadeltaG = +2.8 kcal/mol). Hydrogen
      bonds provided by (Tyr)L32 and (Asp)H56 were also important for binding: mutation
      of (Tyr)L32 to Phe resulted in a significant reduction in binding affinity
      (deltadeltaG = +1.7 kcal/mol). Disruption of hydrophobic interactions (van der
      Waals contacts) led to significant reductions in affinity also ((Tyr)H99 to Ala,
      deltadeltaG = +1.5 kcal/mol; (Leu)L94 to Ala, deltadeltaG > +3.0 kcal/mol). An
      attempt to increase binding affinity by filling a cavity in the interface with a
      larger antibody side chain was unsuccessful, as the free energy gained by new
      antibody-antigen interactions did not compensate for the removal of cavity-bound
      water molecules.

PMID- 9579663
TI  - Glutamate uptake is decreased tardively in the spinal cord of FALS mice.
AB  - This study examined high affinity Na+-dependent uptake of glutamate in
      synaptosomal preparations from spinal cord in mice that express a dominant
      mutation of human copper/zinc superoxide dismutase (SOD1) and represent an animal
      model of amyotrophic lateral sclerosis (ALS). Their muscle strength was also
      monitored by a grip traction test throughout their lifespan. The high affinity
      Na+-dependent uptake of [3H]glutamate was decreased between 120 and 150 days of
      age. A marked and significant decrease in Vmax (-40.2%; p < 0.001) on whole
      spinal cord synaptosomes was observed at 150 days, with no change in Km. This
      significant decrease was reached a week before the animals died (157.2 +/- 2.2
      days) and corresponded to a considerable fall in muscle strength (25% loss
      between 120 and 140 days, p < 0.001). The FALS mouse model therefore reproduces
      the decrease in glutamate uptake reported in humans suffering from sporadic or
      familial ALS. These results are discussed in terms of a possible tardive
      involvement of glutamate uptake deficiency in human ALS.

PMID- 9579664
TI  - Resetting of circadian melatonin and cortisol rhythms in humans by ordinary room
      light.
AB  - The present study was designed to investigate whether a weak photic stimulus can
      reset the endogenous circadian rhythms of plasma melatonin and plasma cortisol in
      human subjects. A stimulus consisting of three cycles of 5 h exposures to
      ordinary room light (approximately 180 lux), centered 1.5 h after the endogenous
      temperature nadir, significantly phase-advanced the plasma melatonin rhythm in
      eight healthy young men compared with the phase delays observed in eight control
      subjects who underwent the same protocol but were exposed to darkness (p < or =
      0.003). After light-induced phase advances, the circadian rhythms of plasma
      melatonin and plasma cortisol maintained stable temporal relationships with the
      endogenous core body temperature cycle, consistent with the conclusion that
      exposure to ordinary indoor room light had shifted a master circadian pacemaker.

PMID- 9579665
TI  - Circadian expression of pineal 5-lipoxygenase mRNA.
AB  - In lymphocytes, the pineal hormone, melatonin, suppresses 5-lipoxygenase (5-LO)
      gene expression. Because circadian fluctuations in melatonin content are
      prominent in the pineal, we hypothesized that 5-LO mRNA level in this gland is
      greater when melatonin is low (day) than at night. Using the reverse
      transcription/polymerase chain reaction we assayed the levels of mRNAs coding for
      5-LO, serotonin N-acetyltransferase (NAT), and for a constitutive gene,
      cyclophilin, in rat pineals obtained at 10:30-11:00 h (day) or 24:30-01:00
      (night). Cyclophilin mRNA was not affected by circadian rhythm, whereas 5-LO and
      NAT were affected in an opposite manner: 5-LO mRNA was high during the day, NAT
      mRNA at night. We propose that circadian pineal 5-LO expression might play a role
      in circadian regulation of pineal functioning.

PMID- 9579666
TI  - Regulation of attention to novel stimuli by frontal lobes: an event-related
      potential study.
AB  - This study examined the relationship between orienting responses to novel events
      and subsequent exploratory behavior. The N2-P3 electrophysiologic component of
      the orienting response was found to be larger for novel than repetitive
      background stimuli. Across subjects, the amplitude of this N2-P3 response in
      frontal regions strongly predicted the proportional increase in the duration of
      viewing directed toward novel compared to background stimuli. Within subjects,
      larger N2-P3 amplitudes in response to novel stimuli were associated with longer
      viewing durations on those stimuli. These results suggest that the N2-P3
      component of the orienting response reflects the activity of a neural system
      involving frontal networks that dynamically regulates the subsequent allocation
      of attentional resources to novel stimuli.

PMID- 9579667
TI  - Liposomal transfection efficiency and toxicity on glioma cell lines: in vitro and
      in vivo studies.
AB  - To evaluate the influence of cell type and cationic liposomal formulation on gene
      transfection efficiency three liposomes (lipofectin, lipofectamine and DOTAP)
      were used to transfect the human (A172 and MOG-G-CCM) and rodent (C6 and A15A5)
      glioma cell lines with the Lac Z gene. Parallel studies evaluated in vitro
      cytotoxicity and the neuropathological changes following intracerebral injection.
      The transfection efficiency and cytotoxicity of the liposomes varied both
      quantitatively and qualitatively between the cell lines. There were no
      behavioural disturbances following intrastriatal or hippocampal injection and the
      neuropathological changes at the injection sites were focal and similar for all
      liposomes. The influence of glial cell lineage on both liposomal transfection
      facility and cytotoxicity may have important implications for in vivo gene
      transfection in the central nervous system.

PMID- 9579668
TI  - Optical recording of responses to frequency-modulated sounds in the auditory
      cortex.
AB  - Using an optical recording method with a voltage-sensitive dye, we recorded
      activities in the primary auditory cortex (AI) of anesthetized guinea pigs in
      response to frequency-modulated (FM) sounds and sounds with stepwise changes in
      frequency (SF). Responses to the FM sound showed a spatiotemporal pattern in
      which a localized active spot traversed the isofrequency bands in the AI, and
      they differed from the band-like responses to the SF sound. These results
      indicate that time-varying sounds are represented as spatiotemporal activation of
      tonotopic organization in the AI by spectral cues with interactions between
      frequency bands.

PMID- 9579669
TI  - Cortical anatomy of mental imagery of concrete nouns based on their dictionary
      definition.
AB  - The functional anatomy of the interactions between spoken language and visual
      mental imagery was investigated with PET in eight normal volunteers during a
      series of three conditions: listening to concrete word definitions and generating
      their mental images (CONC), listening to abstract word definitions (ABST) and
      silent REST. The CONC task specifically elicited activations of the bilateral
      inferior temporal gyri, of the left premotor and left prefrontal regions, while
      activations in the bilateral superior temporal gyri were smaller than during the
      ABST task, during which an additional activation of the anterior part of the
      right middle temporal gyrus was observed. No activation of the occipital areas
      was observed during the CONC task when compared either to the REST or to the ABST
      task. The present study demonstrates that a network including part of the
      bilateral ventral stream and the frontal working memory areas is recruited when
      mental imagery of concrete words is performed on the basis of continuous spoken
      language.

PMID- 9579670
TI  - Stimulus predictability and the gap effect on pre-saccadic smooth pursuit.
AB  - There is disagreement in the literature as to whether smooth pursuit latency is
      reduced when a temporal gap is introduced between the extinction of a central
      fixation target and the illumination of an eccentric moving target. This study
      confirms that in human subjects smooth pursuit latency is reduced by gaps and
      that the magnitude of the reduction is related to the duration of the gap.
      However, latency is not solely determined either by visual factors or by task
      parameters such as spatial predictability, but is affected by task context. The
      results suggest a role for non-visual factors such as attention in the initiation
      of pursuit.

PMID- 9579671
TI  - Identification of fucose alpha(1-2) galactose epitope-containing glycoproteins
      from rat hippocampus.
AB  - Fucosylation of terminal galactose residues of brain glycoproteins in the alpha(1
      2) position has been shown to be crucial for neuronal plasticity, including
      phenomena such as long-term potentiation and long-term memory formation. We
      raised antibodies against the plasticity-relevant fucalpha(1-2)gal epitope and
      used them to determine the distribution of the epitope in adult rat hippocampus.
      To identify proteins bearing fucalpha(1-2)gal glycostructures antibodies against
      known synaptic fucoglycoproteins were used in combination with the fucalpha(1
      2)gal antibodies. The NMDA receptor subunit NR1 and fractions of gp65 and
      cadherin were found to carry the epitope, while fucosylation of NCAM180 and
      NCAM140 obviously occurs via different linkages to the glycan chains.

PMID- 9579672
TI  - Stimulation of cerebellum protects hippocampal neurons from global ischemia.
AB  - We investigated whether electrical stimulation of the cerebellar fastigial
      nucleus (FN) can protect pyramidal neurons of the CA1 zone of dorsal hippocampus
      from delayed neuronal death caused by global ischemia. Stimulation of the FN for
      1 h prior to transient 4-vessel occlusion in anesthetized rats salvaged 57% (p <
      0.01) of pyramidal neurons from degeneration. This effect could be
      preconditioned. Sham simulation of FN or stimulation of the rostral ventrolateral
      medulla (RVL) were without effect (p > 0.5). Excitation of intrinsic neuronal
      pathways represented in FN can protect central neurons from global as well as
      focal ischemic degeneration. The brain contains systems designed to protect it
      from ischemia by mechanisms of central neurogenic neuroprotection acting
      independently of actions on cerebral blood flow.

PMID- 9579673
TI  - Inhibition of vasopressinergic neurons by central injection of a specific
      aminopeptidase A inhibitor.
AB  - The brain angiotensin (Ang) system plays an important role in the central control
      of vasopressin release. Using EC33, a selective aminopeptidase A inhibitor which
      blocks the metabolism of Ang II in Ang III, we previously reported that
      vasopressin release was under the control of Ang III and not Ang II. To determine
      accurately the action of EC33, the effects of intracerebroventricular injection
      of Ang peptides or EC33 on extracellular unit activity of vasopressinergic
      neurons in the supraoptic nucleus of urethane-anaesthetized rats were examined.
      Angiotensin II (15-30 ng) or Ang III (15 ng) increased the firing rate of all
      neurons tested. Conversely, EC33 (10 microg) reduced or completely abolished (30
      60 microg) the basal firing rate for 4-6 min in all eight neurons tested. EC33
      (30 microg) also inhibited the activity induced by 30 ng Ang II. It was concluded
      that the observed activity of Ang II required its conversion to Ang III and that
      endogenous Ang III may exert a tonic control on the basal firing level of
      vasopressinergic neurons.

PMID- 9579674
TI  - Left planum temporale surface correlates with functional dominance during story
      listening.
AB  - The relationship between anatomical asymmetry of the planum temporale (PT) and
      functional lateralization for language comprehension was studied in 14 normal
      volunteers, including five left-handers (LH). PT surfaces and asymmetry were
      measured in each subject using structural MRI, while functional lateralization
      was assessed on individual regional cerebral blood flow (rCBF) difference images
      of a PET-H2(15)O activation protocol in which a story listening condition was
      contrasted with a control state. Significant positive correlations were found
      between the left PT surface and the amount of NrCBF increase during the story
      listening in the left superior temporal gyrus as well as with the left-right
      activation index in the superior temporal and the temporal pole. Functional
      imaging data were correlated neither with the right PT surface nor with the right
      left PT surface asymmetry index. However the latter index was correlated with
      handedness scores. The present results indicate that the size of the left PT is
      the relevant anatomical landmark for language dominance, and demonstrate that
      anatomical asymmetries are part of the functional variability for language.

PMID- 9579675
TI  - Visual extinction as a spatio-temporal disorder of selective attention.
AB  - Studies of normal behaviour have shown that the process of selection takes a
      finite time, one measure of which is the attentional dwell time, that is the
      period of interference produced by one attended stimulus on a subsequent one.
      Here we investigated the time for selection in FB, a neurological patient
      suffering from a visuospatial disorder of attention (unilateral extinction). FB
      was asked to identify two letters displayed in rapid succession either to the
      left (damaged), or to the right (intact) visual hemifield. By varying the
      interval between stimuli, we measured how long the first letter continued to
      interfere with accuracy on the second- that is the first letter's attentional
      demand over time. The results showed that the process of selection has an
      abnormal duration in the affected visual field, being at least twice as long as
      in the intact field. We suggest that the slowed visual processing for the
      contralesional object may contribute to the competitive bias against that object
      which is the hallmark of unilateral extinction.

PMID- 9579676
TI  - Differential macrophage responses following pre- and postganglionic axotomy.
AB  - Here we report that macrophages in the rat superior cervical ganglia (SCG)
      respond differently to pre- and postganglionic axotomy. Postganglionic axotomy
      results in a rapid activation of resident macrophages, as measured by inducible
      nitric oxide synthase (iNOS) immunoreactivity, and a massive invasion by
      macrophages. Following preganglionic lesion there was no such rapid activation
      and the macrophage invasion was of much lower magnitude. A subpopulation of the
      macrophages also expressed haem oxygenase-1 (HO-1). The results are compatible
      with a model in which macrophages or their products, including nitric oxide (NO)
      and carbon monoxide (CO) could be important for induction of early changes in the
      nerve cell body, like an altered neuropeptide synthesis, which has been shown to
      accompany the regenerative response in peripheral ganglia.

PMID- 9579677
TI  - The projection from hippocampal area CA1 to the subiculum sustains long-term
      potentiation.
AB  - Long-term potentiation (LTP) is a popular model of the synaptic plasticity which
      may be engaged by the biological processes underlying learning and memory. Most
      available studies of LTP have concentrated on the analysis of LTP occurring in
      'early' components of the hippocampal circuit (for example, dentate gyrus and
      area CA1). We examine here, for the first time, LTP as it occurs in the massive,
      unidirectional projection from CA1 to the subiculum in vivo. We show that this
      projection sustains high-frequency stimulus-induced LTP (10 trains of 20 stimuli
      at 200 Hz; intertrain interval 2 s; LTP 181 +/- 9% at 30 min post-LTP induction).
      In addition, input-output (I/O) curves show a leftward shift for all stimulation
      values.

PMID- 9579678
TI  - The Brn-3c transcription factor contains a neuronal-specific activation domain.
AB  - Brn-3a, Brn-3b and Brn-3c are closely related POU family transcription factors
      which are expressed predominantly in neuronal cells. Previously Brn-3a has been
      shown to activate a number of gene promoters in co-transfections carried out in
      different cell types, while Brn-3b inhibits the basal activity of these
      promoters. We show here that Brn-3c activates the same promoters as Brn-3a but
      only in co-transfections into neuronal cells and not in other cell types. This
      effect is dependent upon an N-terminal region of Brn-3c which acts as a neuronal
      cell specific activation domain when linked to a heterologous DNA binding domain.
      To our knowledge this is the first report of an activation domain with apparently
      neuronal specific activity.

PMID- 9579679
TI  - Enhanced expression of AMPA receptor protein at perforated axospinous synapses.
AB  - We performed a quantitative electron microscopic analysis of the middle third of
      the molecular layer in the dentate gyrus of rat, using material processed with
      postembedding gold labeling for the glutamate receptor subunits GluR1, GluR2/3,
      or NMDAR1. Perforated axospinous synapses were at least twice as likely as non
      perforated ones to express detectable levels of AMPA receptor subunits, whereas
      no significant differences in NMDA receptor expression were observed. These data
      imply that perforated synapses may be especially potent, and are consistent with
      the hypothesis that insertion of AMPA receptor protein into the postsynaptic
      membrane of previously silent synapses contributes to long-term potentiation.

PMID- 9579680
TI  - Regeneration of axons from central neurons into microchips at the level of the
      spinal cord.
AB  - Axons from central neurons can regenerate into the tissue matrix formed within a
      silicone tube capped with two pieces of peripheral nerve, one of which had been
      sutured to a lesion in the spinal cord. Such axons can grow through a
      transversely positioned microchip in the tube. These observations suggest that it
      is feasible to establish functional contact between external electronic equipment
      and regenerating central nervous axons making it possible to monitor and control
      their electrical activity. The findings open new perspectives for restoration of
      motor and sensory functions following spinal cord lesions.

PMID- 9579681
TI  - Thalamic deactivation during early implicit sequence learning: a functional MRI
      study.
AB  - Previous research has implicated the striatum in implicit sequence learning.
      However, imaging findings have been inconsistent with regard to activity within
      the thalamus during performance of such tasks. Contemporary models of cortico
      striato-thalamic circuitry suggest opposing influences on thalamic activity;
      suppression of thalamic activity is mediated by the indirect pathway and
      enhancement is mediated by the direct pathway. Using functional magnetic
      resonance imaging, we studied activity within human thalamus during early and
      late phases of an implicit sequence learning task known to reliably recruit the
      striatum. Significant deactivation (decreased signal relative to a baseline
      condition) was observed within the thalamus during early implicit learning. This
      finding is consistent with models of cortico-striato-thalamic function and
      specifically supports a profile of early 'thalamic gating' via the indirect
      pathway.

PMID- 9579682
TI  - Mitogen-activated protein kinases activated by lipopolysaccharide and beta
      amyloid in cultured rat microglia.
AB  - To test whether mitogen-activated protein kinases (MAPKs) are involved in
      microglial activation, pure microglia prepared from 1- to 3-day-old rat brains
      were activated with either 100 ng/ml lipopolysaccharide (LPS) or 5 nM synthetic
      beta-amyloid (Abeta) (25-35). The patterns of MAPK activation following LPS and
      Abeta treatment were very similar. Three MAPK subtypes, p38, extracellular signal
      regulated kinase (ERK) and c-Jun N-terminal kinase/stress-activated protein
      kinase (JNK/SAPK) were activated within 15 min and the activities of p38 and ERK
      were rapidly reduced to background level within 30 min while that of JNK was
      maintained for over 1 h. Both inhibitors of p38 (SB203580) and ERK pathway
      (PD098059) reduced LPS-induced nitric oxide (NO) release and Abeta-induced tumor
      necrosis factor-alpha (TNF-alpha) release. Furthermore, co-treatment of SB203580
      and PD098059 additively reduced NO and TNF-alpha release. These results suggest
      that MAPK, at least p38 and ERK, mediate LPS-, and Abeta-induced microglial
      activation.

PMID- 9579683
TI  - Acidosis reduces neuronal apoptosis.
AB  - Acidosis is a well established concomitant of tissue ischemia. Acidosis in the pH
      range 6.0-7.0 is seen in cerebral ischemia and within solid tumors. Extracellular
      acidosis of pH 6.0 and 6.4 provided essentially complete protection from 48 h
      serum deprivation induced apoptotic death of cultured primary murine neurons. We
      tested the effect of p53 using transformed mouse embryo fibroblasts of either
      p53+/+ or p53-/- genotype. Both were markedly protected from serum deprivation by
      acidity. Hypoxia induced fibroblast injury was also reduced at pH 6.8. Lower pH
      resulted in a shift from apoptotic to necrotic morphology after 42 h hypoxia.
      Acidosis reduces apoptosis of both normal and transformed cells, irrespective of
      p53 status.

PMID- 9579684
TI  - Involvement of dendritic adhesion molecule telencephalin in hippocampal long-term
      potentiation.
AB  - Telencephalin (TLCN) is a cell adhesion molecule belonging to the immunoglobulin
      superfamily whose expression is restricted to neurons within the most highly
      developed brain segment, telencephalon. Immunoelectronmicroscopic study revealed
      that in the hippocampal CA1 region, TLCN was localized at the surface membrane of
      postsynaptic spines of pyramidal cell dendrites but not at that of axonal
      terminals. Blocking of TLCN function using anti-TLCN antibody or recombinant
      soluble TLCN protein caused a striking suppression of the long-term potentiation
      (LTP) at the Schaffer collateral-CA1 synapses. The suppression was observed even
      when the blocking was initiated immediately after the tetanic stimuli. These
      observations suggest a role for TLCN-mediated cell-cell interactions as a key
      step in the development of LTP.

PMID- 9579686
TI  - Neural networks for generation and suppression of alpha rhythm: a PET study.
AB  - To study neuronal activities that influence the generation of the alpha rhythm,
      we used positron emission tomography and simultaneous recording of the
      electroencephalogram (EEG) in normal volunteers and under passive conditions. A
      negative correlation between regional cerebral blood flow and alpha power was
      found in the occipital cortex, consistent with the visual modality-specific
      reactivity of the alpha rhythm. A positive correlation was found in the pons,
      midbrain, hypothalamus, amygdala, the basal prefrontal cortex, insula and the
      right dorsal premotor cortex. Neuronal activities of the brain stem and limbic
      system that are positively correlated with alpha power may provide an anatomical
      basis for studies of the relationship between emotional state and brain rhythm in
      health and disease.

PMID- 9579685
TI  - Haptic information differentially interferes with visual analysis in reaching
      grasping control and in perceptual processes.
AB  - We used an interference paradigm in order to study integration between haptic and
      visual information in motor control and in perceptual analysis. Subjects either
      reached and grasped a visually presented sphere or matched its size with their
      left hand while manipulating with their right hand another sphere whose size
      could be smaller or greater. In four experiments haptic analysis of the
      manipulated sphere could be either automatically incorporated with or explicitly
      dissociated from visual analysis. In a fifth experiment reaching-grasping and
      matching were executed with the right hand, whereas manipulation was executed
      with the left hand. Manipulation with the right hand influenced finger shaping
      during grasping with the left hand when the sizes of the two objects were
      different. Interference was observed mainly in those experiments in which haptic
      analysis could be automatically integrated with visual analysis. In the matching
      task, no effect was observed. Finally, manipulation with the left hand did not
      produce any interference effect on reaching-grasping and matching executed by the
      right hand. The results of the present study suggest that somesthetic information
      is integrated with visual information only in sensorimotor transformations. In
      addition, they support the notion that the left hemisphere together with the
      right hemisphere is involved in the control of left hand reaching-grasping
      movements.

PMID- 9579687
TI  - Task-dependent laterality for cue decoding during spoken language processing.
AB  - The task-dependent laterality of the auditory cortices was investigated by
      measuring the magnetic fields elicited by three forms of a Japanese verb, which
      differed in terms of prosodic and phonetic cues. Significant task-dependent
      magnetic fields were found in both hemispheres during a prosody-related task, but
      only in the left during a phoneme-related task. The latency was similar to the
      mismatch negatively which reflects the neural activity of automatic cue decoding.
      These results suggest that task-dependent schemata are activated at least
      partially in parallel with automatic cue-decoding processes such that those in
      the left hemisphere process linguistic information irrespective of acoustic cues
      whereas those in the right hemisphere process prosodic information.

PMID- 9579688
TI  - Neurotrophin-3 and trkC in muscle are non-essential for the development of mouse
      muscle spindles.
AB  - Neurotrophin-3 (NT3) or TrkC null mutant mice were examined for the presence of
      muscle spindles. Muscles of mastication, but not limbs, contained spindles in
      newborn and adolescent mutants. The intramuscular distribution and morphological
      properties of spindles in mutant masticatory muscles were indistinguishable from
      those of wild-type spindles. Intrafusal fibers of NT3- or trkC-deficient spindles
      expressed the slow-tonic isoform of myosin heavy chains, characteristic of wild
      type spindles. Sensory nerve endings were observed in spindles of mutants by
      electron microscopy. Thus, NT3 or trkC, which is expressed in wild-type spindles,
      may serve functions other than those related to spindle assembly. Presumably,
      proprioceptive neurons innervating jaw muscles are dependent on factors other
      than NT3 for survival and maintenance.

PMID- 9579689
TI  - BetaAPP gamma-secretase and SREBP site 2 protease are two different enzymes.
AB  - The cleavage process of sterol regulatory element binding proteins (SREBPs)
      shares several characteristics with that of beta-amyloid precursor protein
      (betaAPP). We studied the secretion of amyloid beta protein (Abeta) from mutant
      M19 Chinese hamster ovary (CHO) cells that are defective in the site 2 cleavage
      of SREBPs. The levels as well as the C-terminal properties of Abeta secreted from
      M19 cells were similar to those from wild-type CHO cells, demonstrating that
      gamma-cleavage of betaAPP occurs normally in M19 cells. The present data
      indicated that gamma-secretase of betaAPP and SREBP site 2 protease are distinct
      enzymes.

PMID- 9579690
TI  - Prostaglandin-D-synthase (beta-trace protein) levels in rat cerebrospinal fluid.
AB  - The precise role of prostaglandin-D-synthase (beta-trace protein), the major
      constituent of cerebrospinal fluid, is unclear. In the present study, a sensitive
      and highly specific fluoroimmunoassay was developed. The measurement of the
      enzyme levels in rat CSF revealed a developmental change in the CSF levels with
      the highest value of 66 +/- 8 microg/ml at 7 days after birth. No significant
      difference in the levels was seen between different times of day. Subcutaneous
      injections of all-trans retinoic acid caused a dramatic decrease in the protein
      levels in a dose- and time-dependent manner. These findings may raise the
      possibility that prostaglandin-D-synthase in CSF is involved in retinoic acid
      action on the brain.

PMID- 9579691
TI  - Olfactory neurons are protected from apoptosis in adult transgenic mice over
      expressing the bcl-2 gene.
AB  - The olfactory system provides a useful in vivo model for studying neuronal
      apoptosis. The synaptic target deafferentation (olfactory bulb ablation) of the
      sensory epithelium induces a massive and synchronous wave of retrograde apoptosis
      in the large population of olfactory sensory neurons. The proto-oncogene bcl-2 is
      involved in the regulation of cell death and is able to block apoptosis in
      motoneurones. We demonstrate here that olfactory neurons over-expressing the
      human Bcl-2 protein in transgenic mice are long-term protected from apoptotic
      death following ipsilateral olfactory bulbectomy. We kinetically assessed
      neuronal death 32 h, 50 h and 5 days following unilateral olfactory bulbectomy,
      in adult C57BL6 (wild-type) and transgenic mice with olfactory neurons over
      expressing the Human bcl-2 gene. Using the TUNEL method and morphometric analysis
      of olfactory epithelium, we confirmed the occurrence of a wave of neuronal death
      in wild-type mice but failed to detect a significant rate of neuronal apoptosis
      in the olfactory epithelium of transgenic animals. Apoptotic death of olfactory
      neurons probably shares common pathways with apoptotic processes occuring in
      other neuronal types, including motoneurons.

PMID- 9579692
TI  - Neuronal protection of oligodendrocytes from antibody-independent complement
      lysis.
AB  - Cultured rat oligodendrocytes are lysed by complement via antibody-independent
      activation of the classical pathway. This susceptibility to complement lysis has
      been demonstrated to be due to lack of CD59, a complement regulatory protein
      which inhibits assembly of the membrane attack complex. In this study the effects
      of homologous and heterologous complement were examined in a co-culture system of
      rat oligodendrocytes and peripheral neurones, where axonal ensheathment was
      observed as early as 4 days after the addition of glial progenitors to the
      neurones. Following exposure to complement, ensheathing oligodendrocytes were
      markedly less sensitive to antibody-independent but not antibody-dependent
      complement lysis than were cells grown without neurones. Immunocytochemical data
      revealed that co-cultured oligodendrocytes remained CD59 negative, but in
      contrast to oligodendrocytes cultured alone, were negative for C3b when incubated
      with C7-deficient serum. Taken together these data indicate that the decreased
      sensitivity of co-cultured oligodendrocytes to complement lysis is not attributed
      to the increased expression of CD59, but rather in a failure to activate
      complement. Incubation of oligodendrocytes with neurone-conditioned medium
      afforded significant protection (68%), against antibody-independent complement
      attack, suggesting that soluble neuronal factors can protect oligodendrocytes
      from complement-mediated lysis.

PMID- 9579693
TI  - Estrogen receptor alpha is essential for induction of oxytocin receptor by
      estrogen.
AB  - The induction of oxytocin receptor (OTR) synthesis in the periphery and in the
      brain by estrogen is critical for reproductive success. Oxytocin receptors are
      involved in the control of parturition, milk ejection, and sexual and maternal
      behaviors. The discovery of a second estrogen receptor (ERbeta) in the brain and
      the failure of in vitro transcription studies using OTR promoter constructs to
      replicate the in vivo transcriptional regulation have raised questions regarding
      the molecular mechanisms involved in the regulation of the OTR gene by estrogen.
      Using mice genetically deficient in estrogen receptor alpha (ERalpha), we
      demonstrate that ERalpha is not necessary for basal OTR synthesis, but is
      absolutely necessary for the induction of OTR binding in the brain by estrogen.

PMID- 9579694
TI  - Long-term effects of status epilepticus induced by kainic acid on hippocampal
      polyamines.
AB  - Putrescine has been suggested to have an inhibitory effect on the excitability of
      the central nervous system. In the present study we found that 2 and 3 weeks
      after status epilepticus induced by kainic acid, rats had increased
      concentrations of putrescine (3- and 1.7-fold, respectively) and spermidine (1.6-
      and 1.4-fold, respectively) in the hippocampus. These animals exhibited a higher
      susceptibility to pentylentetrazol than the saline group. In addition, several
      hours after the pentylentetrazol injection, the concentration of putrescine and
      spermidine increased again in the brain and also in the plasma. In conclusion,
      increased hippocampal putrescine and spermidine concentrations seem to be linked
      with a lower threshold of excitability.

PMID- 9579696
TI  - Repetitive optical stimulation elicits fast receptive field changes in mature
      visual cortex.
AB  - Fast associative cellular plasticity of visual cortical cells has been shown in
      vitro with electrical stimulation as well as in vivo by pairing of natural
      stimuli with artificial depolarization. Here we experimentally changed receptive
      field properties of single cells in the mature cat visual cortex with purely
      natural associative stimulation in vivo. Single cortical cells expanded their
      receptive fields within minutes into unresponsive regions and changed their
      functional receptive field structure for hours after associative co-stimulation
      of active and primarily unresponsive regions. The effects are interpreted as
      strengthening of subthreshold synaptic inputs. Repetitive stimulation with the
      same visual pattern can modify single cell properties in vivo within minutes and
      may be related to preattentive fast perceptual learning.

PMID- 9579695
TI  - Imaging brain activation induced by long trains of repetitive transcranial
      magnetic stimulation.
AB  - Using positron emission tomography (PET), we measured the relative changes in
      regional cerebral metabolic rate of glucose (rCMRglc) during 2 Hz repetitive
      transcranial magnetic stimulation (rTMS) of the left sensorimotor cortex (SM1)
      and during imitation of rTMS-induced arm movements. Such stimulation caused an
      rCMRglc increase of about 8% within the SM1. The relative rCMRglc increase within
      SM1 was significantly greater in magnitude and larger in area during voluntary
      imitation of rTMS-induced arm movements. Moreover, the rostral part of the SMA
      was significantly more activated by voluntary movements than during rTMS.
      Combining rTMS and PET has the potential to visualize rTMS-related net brain
      activation, and may open up new possibilities for functional network analysis by
      comparing willed brain activation with electromagnetic brain activation.

PMID- 9579697
TI  - Seasonal mood change and personality: an investigation of genetic co-morbidity.
AB  - Clinical observations and empirical studies suggest that Seasonal Affective
      Disorder (SAD) is related to personality. The present study estimates the genetic
      and environmental correlations between the Global Seasonality Score (GSS) from
      the Seasonal Pattern Assessment Questionnaire and personality measures, assessed
      using the NEO Five Factor Inventory (NEO-FFI) and the Dimensional Assessment of
      Personality Pathology (DAPP) in a volunteer sample of 163 monozygotic (MZ) pairs
      (102 female and 61 male pairs) and 134 dizygotic (DZ) pairs (70 female, 38 male
      and 26 opposite-sex pairs). Large genetic correlations were found between the GSS
      and NEO-FFI Neuroticism (0.52: 95% CI = 0.36-0.71) and DAPP-BQ Cognitive
      Dysregulation (0.50: 95% CI = 0.30-0.71), Affective Lability (0.49: 95% CI = 0.29
      0.77), Anxiousness (0.37: 95% CI = 0.18-0.55) and Stimulus Seeking (0.45: 95% CI
      = 0.25-0.64) scales. The genetic correlations with the remaining scales, such as
      Extraversion (0.06: 95% CI = -0.16-0.26), Compulsivity (-0.09: 95% CI = -0.31
      0.12) and Submissiveness (0.15: 95% CI = -0.05-0.34) were uniformly small. All
      environmental correlations between the GSS and personality scales were < or =
      0.19. These results provide evidence that the observed correlations between these
      seasonality and personality dimensions are attributable to common genetic factors
      and that environmental influences are domain specific.

PMID- 9579698
TI  - The influence of climate on suicidal behaviour in Italy.
AB  - A growing number of studies report an asymmetry in the seasonal distribution of
      suicides, with a peak in the late spring months for both sexes. The aim of this
      study is to verify if the climate, apart from its seasonal change, exerts a
      direct influence on suicidal behaviour. To this end, deaths by suicide in 17
      Italian towns which all have a meteorologic station have been analyzed, taking
      into account some climatic indicators. Results of analyses show an unequal
      distribution of suicides with respect to latitude, with a peak in the North. The
      distribution of deaths by suicide shows a negative relationship with mean yearly
      temperature values, max and min, and with sun exposure indicators, and a
      positive, but less significant relationship with rainfall values. As far as
      climatic variables considered as a whole are concerned, stepwise regression
      identifies three relevant factors with significant relationships to suicide
      rates: humidity grade, rainfall mean, and sunlight exposure. These three climatic
      indicators explain up to 63% (Adj R2) of the variance in the distribution of
      suicide rates for both genders, with sunlight exposure offering the most
      significant contribution, when regressed on suicide rates via a multiple
      regression model. Higher suicide rates, therefore, correspond to dry places which
      are less exposed to the sun. However, the variable which shows the most
      significant correlation with suicide rates for both sexes is not a climatic one,
      but the percentage of the population aged 65 and over. The distribution of people
      at greater biological risk for possible disruption of brain neurochemistry (i.e.
      older people), therefore, predicts the distribution of suicide rates. Climate
      contributes to this biological risk by modifying both the responsiveness of the
      circuits that control mood and behaviour, and also the frequency and intensity of
      social interaction.

PMID- 9579699
TI  - Frontal lobe dysfunction in obsessive-compulsive disorder and major depression: a
      clinical-neuropsychological study.
AB  - Neuropsychological findings support a hypothesized relationship between obsessive
      compulsive disorder (OCD) and the frontal lobe. The aim of the present study was
      to compare findings of neuropsychological tests of frontal lobe function in 28
      OCD patients and 29 patients with major depressive disorder (MDD), all diagnosed
      according to DSM III-R criteria. The patient groups were homogeneous for
      educational level, handedness, duration of illness, and sex distribution. All 57
      subjects received a battery of tests sensitive to frontal lobe dysfunction as
      well as the Wechsler Memory Scale (WMS). Clinical symptomatology in the MDD and
      OCD groups was assessed with the Hamilton Rating Scale for Depression and the
      Yale-Brown Obsessive-Compulsive Scale, respectively. The only significant
      difference between the two diagnostic groups for any of the neuropsychological
      indices, with age as a covariate, was in the Object Alternation Test, in which
      OCD patients had a significantly higher number of perseverative responses. Test
      performances were not correlated with clinical symptomatology or severity of
      illness. Our preliminary results confirm the hypothesis that there is a selective
      impairment of orbito-frontal cortex in OCD and seem to exclude the existence of
      specific frontal lobe dysfunction in MDD, even though the two disorders show
      clinical similarities.

PMID- 9579700
TI  - Semantic priming in major depressive state.
AB  - We studied semantic priming in 20 major depressive subjects. The methodology used
      was a visual lexical decision task. Semantic priming is the facilitation of
      target word recognition (shortening of response time) by the prior presentation
      of a semantically related context (a prime word). It relies on semantic
      processing of words and context, facilitating early cognitive stages of response.
      Varying the temporal interval between prime and target words onset allows us to
      distinguish between two priming mechanisms, relying on more automatic (test 1) or
      more controlled (i.e. attention dependent) (test 2) information processing. We
      observe a significant retardation for words and pseudo-words in depressives (in
      relation to controls) in both tests. In spite of a general retardation and
      increase of response times in depressives, semantic priming is evident in both
      groups and both tests, and does not differ significantly between depressive and
      control groups in either automatic or controlled conditions. Theses results
      confirm that semantic processing is not impaired in depression, and are discussed
      with regard to the hypothesis of an effortful processing impairment in
      depression, and to depressive retardation.

PMID- 9579701
TI  - Cholecystokinin, beta-endorphin and vasoactive intestinal peptide in peripheral
      blood mononuclear cells of drug-naive schizophrenic patients treated with
      haloperidol compared to healthy controls.
AB  - Cholecystokinin (CCK), beta-endorphin (BE), and vasoactive intestinal peptide
      (VIP) in peripheral blood mononuclear cells from 30 drug-naive schizophrenics
      compared to 22 healthy controls were studied. Patients were evaluated with the
      Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive
      Symptoms (SAPS) and the Scale for the Assessment of the Negative Symptoms (SANS)
      at baseline (TO), and after four weeks (T4) in nine patients who were
      subsequently treated with haloperidol (HL). Neuropeptide concentrations in
      peripheral blood mononuclear cells (PBMC) were measured at TO and, for the
      treated patients, at T4. There was a negative correlation between CCK and SANS
      baseline scores and a trend for patients who responded poorly to HL (i.e.
      patients with a prevalence of negative symptomatology) to have lower CCK basal
      values.

PMID- 9579702
TI  - Adaptation of visually guided behavior during reversed vision in schizophrenia: a
      preliminary study.
AB  - This preliminary study evaluated the adaptation of visually guided behavior to
      reversed vision in schizophrenia. The study included 54 patients who met DSM-III
      R criteria for schizophrenia. Visuomotor reaction times (VRTs) during reversed
      vision were measured in six blocks of 35 consecutive trials. The VRTs of
      schizophrenics were compared with those of normal subjects. A good fit (R2 =
      0.9981) for the adaptation process of VRTs during reversed vision was found with
      the equation y = 1030 + 1499/x, where x is the order of the block and y is the
      group mean VRT for each block. The VRTs in schizophrenics were significantly
      slower than those in normal subjects. However, the adaptation process to reversed
      vision essentially did not differ from normal. The adaptation of visually guided
      behavior during reversed vision may involve procedural learning; this task may
      thus be useful in evaluating such learning. The VRTs during reversed vision may
      be related to some aspects of symptoms in the patient with schizophrenia and may
      also be useful in predicting clinical outcome.

PMID- 9579703
TI  - Eye movement abnormalities in anorexia nervosa.
AB  - The aim of the present study is to investigate smooth pursuit eye movement and
      saccadic performance in anorexia nervosa during a restored weight period and to
      determine if functional links can be made between eye movement performance and
      clinical features. SPEM parameters were recorded for 28 female anorectic out
      patients (DSM IV), who had a body weight loss of up to 20% of ideal body weight.
      Twenty-eight comparison subjects were also tested. Clinically, each patient was
      assessed using the Eating Disorder Inventory (EDI), the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS), the Structured Interview for Personality Disorders
      (SCID II), the Symptom Checklist-90-Revised (SCL-90-R) and the Hamilton Scale for
      Depression (HRSD). The anorectic patients performed slightly worse than the
      comparison subjects on a number of SPEM measures. No relationship was found
      between SPEM impairment and a global severity index of psychopathology (SCL 90-R
      GSI) or depressive symptoms. Moreover, OCD symptoms and scores on some EDI scales
      (such as perfectionism) appear related to the severity of the eye movement
      alterations. The evidence of SPEM abnormalities in a subgroup of anorectic
      patients during the remitted state and the relationship of the abnormalities to
      obsessive-compulsive symptoms are discussed. Results are in agreement with the
      hypothesis regarding the persistence of neurophysiological as well as
      psychopathological traits of disorder in anorectic patients.

PMID- 9579704
TI  - Statistical approaches to trial durations in episodic affective illness.
AB  - In light of the high variability in illness characteristics and patterns among
      patients with bipolar illness, parallel group designs present severe methodologic
      difficulties. Crossover, off-on-off-on (B-A-B-A), and other individualized
      designs may be a useful substitute, but no consensus exists about how to estimate
      the individual trial durations required in these instances. Several methods for
      determining optimum trial lengths in crossover designs are presented,
      illustrated, and discussed. These include: chi-square (chi2) for the expected
      versus observed number of either episodes or days well; exceeding two standard
      deviations for average duration of episodes or euthymic intervals; or the
      Sequential Probability Ratio Test (SPRT), which detects when mean values differ
      from prior statistical expectations. Each method was applied to three
      demonstration cases using data from actual clinical trials of three patients with
      different patterns of recurrent affective illness. Each method detected changes
      in illness severity, although different tests appeared to be sensitive to
      differing cycle patterns in the patients illustrated. We suggest that these types
      of analyses and others can be used as indicator statistics to augment global
      impressions and clinical judgment, and to assist in determining individualized
      trial durations, both in formal clinical trials and in clinical treatment
      settings. Once individual responsivity is confirmed with an appropriate interplay
      of trial design and statistical analysis, the percentage response in a given
      population can then be compared to other agents or in other populations.
      Moreover, meta-analytic techniques based on addition of z scores from
      individuals' effect sizes can then be used to assess overall significance of a
      drug effect in a given population or subpopulation. The need for further
      development of appropriate and alternate study designs and analysis methods for
      bipolar illness is highlighted. Approaches to estimating required trial durations
      in individuals with different cycle frequencies in crossover and B-A-B-A designs
      constitute one element of that exploration.

PMID- 9579705
TI  - Decreased heart-period variability in patients with panic disorder: a study of
      Holter ECG records.
AB  - This study investigated cardiac autonomic function in patients with panic
      disorder and normal controls using Holter ECG records. A decrease in ultra-low
      frequency power (< 0.0033 Hz) is known to be associated with an increased risk
      for cardiovascular mortality in humans. Twenty-four-hour ECG was recorded in 29
      patients with panic disorder and 23 normal controls using Holter records. Data
      for 20 h and also 20000 s of awake and 20000 s of sleep periods were analyzed
      using spectral analysis to quantify absolute and relative heart-period
      variability in ultra low (ULF: < 0.0033 Hz), very low (VLF: 0.0033-0.04 Hz), low
      (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency bands. The patients with
      panic disorder had significantly lower total and absolute ULF power, which was
      more pronounced during sleep. The patients also had significantly lower relative
      ULF power and significantly higher relative LF power during sleep. There was a
      significant increase of relative LF power from awake to sleep period only in the
      patient group. The decrease in total and ULF power may increase the risk of
      mortality and sudden arrhythmic death in patients with panic disorder if they
      experience a cardiac event. The higher relative LF power during sleep also
      suggests a possible higher sympathetic drive in the patients during sleep.

PMID- 9579706
TI  - Quantitative EEG (QEEG) predicts relapse in patients with chronic alcoholism and
      points to a frontally pronounced cerebral disturbance.
AB  - The capability of predicting relapse in chronic alcoholism using quantitative EEG
      was investigated. For this purpose, 78 in-patients with alcoholism underwent EEG
      recordings (eyes closed) 7 days after the beginning of detoxification.
      Additionally, other clinical evaluations were carried out. After discharge from
      hospital, patients were regularly re-evaluated for the duration of 3 months in
      order to determine whether they relapsed or abstained from alcohol during this
      time. For classification of the two diagnostic subgroups (relapsers vs.
      abstainers), multivariate discriminant analysis as well as artificial neural
      network technology has been applied. Correct classification of patients' EEGs was
      achieved in 83-85% and thus outperformed classification with clinical variables
      considerably. Furthermore, artificial neural networks (ANN) improved
      classification results when compared with discriminant analysis. It was found
      that, in comparison to abstainers, relapsers had EEGs that were more
      desynchronized over frontal areas, which was interpreted as a functional
      disturbance of the prefrontal cortex.

PMID- 9579707
TI  - Differences in plasma concentrations of the D- and L-threo methylphenidate
      enantiomers in responding and non-responding children with attention-deficit
      hyperactivity disorder.
AB  - Children with attention-deficit hyperactivity disorder who are categorized as
      responders or non-responders to methylphenidate (MPH) on the basis of their
      electrophysiological P3 response in a selective attention task differ in
      metabolic patterns of the D- and L-threo MPH enantiomers. Non-responders showed
      significantly higher plasma concentrations of both D- and L-threo MPH
      enantiomers.

PMID- 9579708
TI  - Roxithromycin: review of its antimicrobial activity.
AB  - Roxithromycin is a semi-synthetic 14-membered-ring macrolide antibiotic in which
      the erythronolide A lactone ring has been altered to prevent inactivation in the
      gastric milieu. The in-vitro activity of roxithromycin is well documented and
      similar to that of other macrolide antibiotics. Roxithromycin is active against
      gram-positive and gram-negative cocci, gram-positive bacilli and some gram
      negative bacilli, but has no significant effect on the predominant faecal flora.
      It also displays good activity against atypical pathogens, such as Mycobacterium
      avium complex, Helicobacter pylori and Borrelia spp. It penetrates and
      accumulates within cells, such as macrophages and polymorphonuclear neutrophils
      (PMNs), where it is distributed between the cytosol and cellular granules. Once
      inside the cells, it is active against intracellular pathogens, such as
      Legionella, Chlamydia, Mycobacterium, Rickettsia and Borrelia spp. Like other
      macrolides, roxithromycin displays a significant post-antibiotic effect which is
      dependent on the pathogens under study, the concentration of roxithromycin and
      the duration of exposure. In vivo, roxithromycin is as effective or more
      effective than other macrolides in a wide range of infections.

PMID- 9579709
TI  - The comparative in-vitro activity of roxithromycin and other antibiotics against
      Bordetella pertussis.
AB  - In spite of vaccination programmes, whooping cough epidemics continue to occur.
      The disease affects all age groups, although its severity is greatest in the
      young, with infants being particularly vulnerable. Erythromycin is generally
      accepted as the drug of choice both for treatment and for prophylaxis during
      epidemics. Roxithromycin is a macrolide with pharmacokinetic advantages over
      erythromycin; it is well absorbed, produces high serum concentrations, has a long
      half-life and penetrates respiratory secretions well. There are no accepted
      standards for testing the sensitivity of Bordetella pertussis to antibiotics, and
      reports of the activity of roxithromycin and erythromycin are variable. Using
      Isosensitest agar supplemented with 5% horse blood and an inoculum of 10(4) cfu,
      88 strains of B. pertussis were tested for their sensitivity to roxithromycin,
      erythromycin, rifampicin and trimethoprim/sulphamethoxazole. The range of MICs
      was 0.12-0.5 mg/L for both roxithromycin and erythromycin. Roxithromycin was
      bactericidal, with an MBC of 1 mg/L (as compared with 0.5 mg/L for erythromycin).
      Since roxithromycin is well tolerated by children when used for respiratory tract
      infections, the good in-vitro activity against B. pertussis, combined with its
      favourable pharmacokinetics, suggest it may be a good candidate for use in the
      treatment and prophylaxis of whooping cough.

PMID- 9579710
TI  - Synergic interactions of macrolides and proton-pump inhibitors against
      Helicobacter pylori: a comparative in-vitro study.
AB  - Thirty-eight clinical strains of Helicobacter pylori were isolated from patients
      with chronic gastritis and gastroduodenal ulceration, and their susceptibility to
      macrolide antibiotics (roxithromycin, flurithromycin, azithromycin, erythromycin)
      in combination with proton-pump inhibitors (lansoprazole and omeprazole) and
      bismuth subcitrate was assayed. Chequerboard titration was used to analyse the
      results of antimicrobial interactions and showed that the activity of macrolides
      was enhanced by combining them with lansoprazole, omeprazole or, to a lesser
      extent, bismuth subcitrate. While the interactions between erythromycin and the
      proton-pump inhibitors or bismuth subcitrate were always additive, the
      combinations of roxithromycin-lansoprazole, flurithromycin-omeprazole and
      azithromycin-lansoprazole acted synergically on 82%, 60% and 60% of H. pylori
      strains, respectively. These results may, in part, account for the enhanced
      clinical efficacy of macrolides administered with proton-pump inhibitors in the
      treatment of H. pylori-associated diseases.

PMID- 9579711
TI  - Anti-inflammatory activity of macrolides: a new therapeutic potential?
AB  - The important role played by macrolides in the chemotherapy of infectious
      diseases is well established, but there is still much speculation about their
      anti-inflammatory potential. A review of in-vitro and ex-vivo studies reported in
      the literature shows that macrolides have potentially relevant immunomodulatory
      effects. In-vitro data suggest that erythromycin A derivatives have a direct
      effect on neutrophil function and the production of cytokines involved in the
      inflammation cascade. The ex-vivo results indicate that short-term administration
      of macrolides may enhance the immune response while long-term administration
      results in immunosuppression. Further research is required to improve our
      understanding of the therapeutic activity of macrolides.

PMID- 9579712
TI  - Comparative anti-inflammatory effects of roxithromycin, azithromycin and
      clarithromycin.
AB  - There are many published reports on the anti-inflammatory effects of macrolides,
      some dating back to the introduction of erythromycin. Macrolides have been shown
      to affect a number of the processes involved in inflammation, including the
      migration of neutrophils, the oxidative burst in phagocytes and the production of
      various cytokines, although the precise mechanisms are not clear. These effects
      have been linked to the ability of macrolides to accumulate in mammalian cells.
      Roxithromycin, a macrolide with better plasma concentrations and higher tissue
      concentrations than erythromycin, has been tested in a standard animal model used
      for evaluating anti-inflammatory drugs. When rats were given a prophylactic dose
      (20 mg/kg), roxithromycin suppressed the oedema produced by injecting carrageenin
      into the paw with effects almost equal to that seen with the non-steroidal anti
      inflammatory drug nimesulide. Azithromycin and clarithromycin, macrolides with
      better pharmacokinetics than erythromycin, only showed slight anti-inflammatory
      effects. These results confirm that roxithromycin has anti-inflammatory
      properties in vivo and encourage the investigation of its mode of action.

PMID- 9579713
TI  - Inhibitory effect of roxithromycin on adhesion of Klebsiella pneumoniae strains
      3051, CF504 and LM21.
AB  - The effect of subinhibitory concentrations of roxithromycin on the adhesion of
      three strains of Klebsiella pneumoniae to Int-407 cells was studied. Adherence
      was markedly inhibited and the effect was increased when roxithromycin was added
      to the cell culture medium rather than to the bacterial growth medium. Several
      assays were performed in order to understand the mechanism by which roxithromycin
      exerted this inhibitory effect. The greatest effect was obtained when
      roxithromycin was concentrated in the extracellular compartment; when
      roxithromycin was concentrated in the intracellular compartment, the inhibitory
      effect was reduced. The analysis of adhesion factors of bacteria showed that
      exposure to roxithromycin did not alter their apparent structure or quantity.
      Roxithromycin appears to interfere in the interaction between bacteria and
      eukaryotic receptors.

PMID- 9579714
TI  - Experimental evaluation of roxithromycin combined with dapsone or
      sulphamethoxazole on Pneumocystis carinii and Toxoplasma gondii dual infections
      in a rat model.
AB  - We have developed a dual infection model in immunosuppressed rats for evaluating
      drugs against Pneumocystis carinii and Toxoplasma gondii, two important
      opportunistic pathogens in patients with AIDS. Using this model, we reported that
      the macrolide roxithromycin was effective at a daily dose of 400 mg/kg in
      preventing the development of T. gondii infection but did not have a prophylactic
      effect against P. carinii in the same rats. A lower dose (200 mg/kg/day) had only
      marginal effects. Extending these experiments, we have now shown that
      roxithromycin at doses of 400 or 200 mg/kg/day combined with dapsone at doses of
      5, 25 or 50 mg/kg/day completely prevented the development of T. gondii
      infection, with no parasites being detected in any of the tissues sampled.
      Roxithromycin at either dose combined with dapsone at 25 or 50 mg/kg/day was also
      effective in preventing the development of P. carinii infection in the lungs. The
      lowest dose of dapsone (5 mg/kg/day) was not fully effective. Pyrimethamine
      dapsone, a combination used clinically, was tested in the same experiment, and
      gave results comparable to those with roxithromycin-dapsone combinations. In a
      further experiment combining roxithromycin with sulphamethoxazole, roxithromycin
      was effective in preventing the T. gondii infection, even when given at only 200
      mg/kg/day with 20 mg/kg/day of sulphamethoxazole. When the dose of
      sulphamethoxazole was reduced to 2 mg/kg/day and given with roxithromycin 200
      mg/kg/day, T. gondii infection developed in two of the five rats treated. P.
      carinii infection was prevented by sulphamethoxazole at 20 mg/kg/day but not
      completely by 2 mg/kg/day. Roxithromycin also has activity against Mycobacterium
      avium, another important cause of opportunistic infections in AIDS patients, and
      the compound penetrates mammalian cells well. Taken together with the favourable
      pharmacokinetic profile of roxithromycin, these results suggest that it may have
      a clinical utility, when used with other agents, in controlling the development
      of opportunistic infections caused by M. avium complex, T. gondii and P. carinii
      in HIV-infected individuals.

PMID- 9579715
TI  - Computer-aided prediction of macrolide antibiotic concentrations in human
      circulating polymorphonuclear leucocytes.
AB  - The relative in-vivo intracellular concentration of various macrolides in
      phagocytes cannot be directly extrapolated from in-vitro experiments that use a
      fixed and constant extracellular concentration for all compounds, since this
      fails to consider different rates of intracellular penetration, dosage regimens
      and pharmacokinetic data. In the proposed model, which takes into account the
      free plasma concentrations and accumulation characteristics of three antibiotics,
      roxithromycin, azithromycin and erythromycin, we show that roxithromycin and
      azithromycin may reach similar concentrations in human polymorphonuclear
      leucocytes when conditions mimic clinical administration of these drugs, while
      erythromycin concentrations are lower. This approach may be useful to predict the
      behaviour of other drugs or other cells, and to assist in the design of rational
      treatment schemes.

PMID- 9579716
TI  - Efficacy and tolerance of roxithromycin versus clarithromycin in the treatment of
      lower respiratory tract infections.
AB  - In an open, randomized, parallel group study, the efficacy and tolerance of
      roxithromycin 300 mg po od was compared with clarithromycin 500 mg po bd in the
      treatment of 60 patients with lower respiratory tract infections (LRTI). The two
      groups were well-matched demographically. Fifty patients (25 per group) were
      clinically evaluable at the end of the study and a satisfactory response was
      found in 88% of those given roxithromycin and 80% of those given clarithromycin.
      All had received treatment for a minimum of 3 days. Only one (3.3%) of 30
      patients in the roxithromycin group reported adverse events compared with seven
      (23.3%) of 30 in the clarithromycin group. Thus both roxithromycin and
      clarithromycin are effective in the treatment of LRTI but roxithromycin is better
      tolerated (P < 0.05) with the advantage of a once-daily dose.

PMID- 9579717
TI  - Comparison of roxithromycin with cefixime in the treatment of adults with
      community-acquired pneumonia.
AB  - This study compared the efficacy and tolerability of once-daily dosing with
      either roxithromycin or cefixime in previously healthy adult patients aged
      between 18 and 60 with markers of uncomplicated community-acquired pneumonia
      (CAP) in three outpatient clinics in an open, randomized study. Sixty patients
      were enrolled: 17 males and 13 females received roxithromycin 300 mg once daily
      for 8-10 days and 22 males and eight females received 400 mg cefixime once daily
      for the same period. All patients were assessed clinically, radiologically and
      bacteriologically before inclusion, immediately after the study and approximately
      1 month later. The most common pathogen isolated from sputum was Streptococcus
      pneumoniae (in 26 (43%) of 60 patients), with mixed organisms isolated from the
      sputum of 18 (30%) of 60 patients. Staphylococcus aureus, Haemophilus influenzae
      or Moraxella catarrhalis occurred in 11/60 patients, and atypical pathogens were
      detected by serology in 7/26 cases in the roxithromycin group and 3/23 in the
      cefixime group. The severity of infection was rated as mild to moderate at the
      beginning of the trial. At the end of the study treatment period, clinical cure
      rates were 30/30 (100%) for roxithromycin and 28/30 (94%) for cefixime, with one
      patient on cefixime being classed as a partial responder and one patient being
      classed as a failure and withdrawn. However, radiological abnormalities persisted
      in three patients on roxithromycin and one on cefixime. Of the 59 patients who
      completed the study, none required further antibiotic therapy. No abnormal
      laboratory parameters or adverse events were reported in either group.
      Roxithromycin at a daily dose of 300 mg was an effective and well-tolerated
      treatment for the empirical treatment of mild to moderate CAP in this group of
      patients.

PMID- 9579719
TI  - AIDS-related cryptosporidial diarrhoea: an open study with roxithromycin.
AB  - In immunocompromised patients, cryptosporidial diarrhoea is a debilitating and
      potentially life-threatening infection for which no effective specific therapy
      exists. In an uncontrolled study of 24 AIDS patients with diarrhoea exclusively
      due to Cryptosporidium spp., treatment with roxithromycin, 300 mg bd for 4 weeks,
      produced symptomatic improvement of diarrhoea in 79% of cases, with 50% of
      patients achieving complete response. The response rate was 100% in a subgroup of
      five patients with no previous or concomitant opportunistic infections. In
      complete responders, improvement was rapid, occurring within 3-5 days, and the
      duration of response was at least 6 months. Response did not appear to be
      correlated with the degree of immunodeficiency. The most limiting adverse effects
      were abdominal pain (two patients), elevated hepatic enzymes (two patients) and
      abdominal pain with elevated hepatic enzymes (one patient). Minor symptoms, such
      as gastrointestinal upset, occurred in nine patients. We conclude that
      roxithromycin is relatively well tolerated and effective against cryptosporidial
      diarrhoea in AIDS patients. Further studies to optimize dosing regimens are
      required.

PMID- 9579718
TI  - Comparison of roxithromycin with co-amoxiclav in patients with sinusitis.
AB  - In an open, randomized study of 60 patients with acute or recurrent sinusitis,
      the bacteriological and clinical efficacy of roxithromycin 150 mg bd were
      compared with those of po co-amoxiclav (625 mg) tds. Of 52 patients who underwent
      sinus puncture for isolation of causative organisms, 48 had pathogens sensitive
      to both antibiotics. Satisfactory clinical response was obtained in 93.1% (27/29)
      evaluable patients receiving roxithromycin and 88.8% (24/27) receiving co
      amoxiclav. Tolerability was significantly better in the roxithromycin group, with
      1/29 (3.4%) patients in this group experiencing gastrointestinal side-effects,
      compared with 7/27 (25.9%) patients in the co-amoxiclav group (P < 0.05).
      Although the study had limited power to detect differences, roxithromycin
      demonstrated clinical, bacteriological and overall efficacy similar to that of co
      amoxiclav, but with better tolerability. Roxithromycin thus appears to be an
      effective and well-tolerated drug for the treatment of acute and recurrent
      sinusitis.

PMID- 9579720
TI  - Roxithromycin treatment for diarrhoea caused by Cryptosporidium spp. in patients
      with AIDS.
AB  - In view of the action of newer macrolide antibiotics on intracellular protozoa,
      we have investigated the efficacy of roxithromycin in the treatment of
      cryptosporidiosis in 26 patients with AIDS. Cryptosporidiosis was confirmed
      either by faecal examination for parasites (modified Kinyoun method) or by
      detection of the parasite in biopsy material obtained by colonoscopy. Patients
      received oral roxithromycin (300 mg bd) for 4 weeks. Twenty-two patients
      completed the study. At the end of the study, 15 patients (68%) were considered
      to be cured and six patients (27%) improved, and treatment failed in one patient
      (5%). We conclude that roxithromycin is a useful treatment for diarrhoea caused
      by Cryptosporidium spp. associated with AIDS.

PMID- 9579721
TI  - Quantification and distribution of alpha1-adrenoceptor subtype mRNAs in human
      proximal urethra.
AB  - 1. We performed RNase protection assays and in situ hybridization to investigate
      the ratio of the three alpha1-adrenoceptor subtype mRNAs, alpha1a, alpha1b and
      alpha1d, in human proximal urethra, and their localization in urethral cross
      sections. As revealed by the RNase protection assays, alpha1a was the predominant
      subtype mRNA in both male and female urethral samples. Alpha1d mRNA was detected
      only in the female sample, and alpha1b mRNA was not detected in any of the
      samples tested. The ratio of the abundance of the subtype mRNAs,
      alpha1a:alpha1b:alpha1d, was 100:0:0 in the male urethra and 90:0:10 in the
      female urethra. 2. In situ hybridization studies showed no significant
      differences in the cross-sectional distribution of alpha1-adrenoceptor subtype
      mRNAs between male and female urethras. Intense alpha1a staining was observed in
      the smooth muscle of the urethra, but alpha1b and alpha1d staining was much less
      intense. 3. Of the three cloned alpha1 subtypes, alpha1a is the most likely to be
      responsible for the contraction of the human urethra. Owing to the side effects
      of nonselective alpha1 drugs, alpha1-selective drugs may be clinically superior
      to nonselective drugs for the treatment of urethral disorders.

PMID- 9579722
TI  - Pharmacological detection of AMPA receptor heterogeneity by use of two allosteric
      potentiators in rat hippocampal cultures.
AB  - 1. In order to examine whether a recently developed allosteric potentiator for
      AMPA receptors, 4-[2-(phenylsulphonylamino)ethylthio]-2,6-difluoro-phenoxyaceta
      mide (PEPA), can be utilized as an indicator of AMPA receptor heterogeneity, the
      action of PEPA upon the increase of intracellular free calcium ion concentration
      ([Ca2+]i) elicited by AMPA was investigated in rat hippocampal cultures, and the
      action was compared with that of cyclothiazide, a well characterized allosteric
      modulator of AMPA receptors. 2. PEPA dose-dependently potentiated AMPA-induced
      increase of [Ca2+]i. In 90% (72 out of 80) of the cells in which cyclothiazide
      acts, PEPA potentiated the increased [Ca2+]i induced by AMPA with pronounced cell
      to-cell variation in rat hippocampal cultures. 3. The ratio of the potentiation
      by PEPA to the potentiation by cyclothiazide (P/C ratio) also varied with cells
      between 0 and 2.15. It was found that the cultured hippocampal cells consisted of
      multiple populations with different P/C ratios. Among them two populations
      exhibited characteristic P/C ratios; low (0 to 0.15; 27 out of 80 cells, 34%) and
      high (> or = 2.00; 1 out of 80 cells, 1%) P/C ratios. The P/C ratios of the other
      populations were between 0.25 and 1.20, and these cells constituted 65% (52 out
      of 80 cells) of the cells tested. 4. Reverse transcriptase-polymerase chain
      reaction analysis suggested that GluR2-flip, GluR1-flip, GluR2-flop, and GluR1
      flop were abundantly expressed (in this rank order) in the cultures used. 5. In
      Xenopus oocytes expressing GluR1, GluR3, or these subunits plus GluR2, the
      potentiation of AMPA response by PEPA and by cyclothiazide varied with subunit
      and splice-variant combinations, and the P/C ratio was between 0.19 and 2.20.
      Oocytes with low P/C ratios (0.19 to 0.50) and low sensitivity to PEPA
      potentiation (1.9 fold to 6.41 fold) were those expressing flip variants
      predominantly, and oocytes with high P/C ratios (1.8 to 2.2) were those
      expressing flop variants predominantly. Oocytes with intermediate P/C ratios
      (0.51 to 1.20) were those expressing various combinations of flip and flop
      variants, and it was impossible to specify the relative abundance of flip and
      flop variants in these cells. Therefore, the P/C ratio can be used to infer
      subunit/splice variant expression only when the ratio is low or high. 6. These
      results suggest that the potentiation by PEPA alone reveals cell-to-cell
      heterogeneity of AMPA receptors, but a comparison of the actions of PEPA and
      cyclothiazide further facilitates the detection of the heterogeneity.

PMID- 9579723
TI  - ATP stimulation of Ca2+ -dependent plasminogen release from cultured microglia.
AB  - 1. ATP (10-100 microM), but not glutamate (100 microM), stimulated the release of
      plasminogen from microglia in a concentration-dependent manner during a 10 min
      stimulation. However, neither ATP (100 microM) nor glutamate (100 microM)
      stimulated the release of NO. A one hour pretreatment with BAPTA-AM (200 microM),
      which is metabolized in the cytosol to BAPTA (an intracellular Ca2+ chelator),
      completely inhibited the plasminogen release evoked by ATP (100 microM). The Ca2+
      ionophore A23187 induced plasminogen release in a concentration-dependent manner
      (0.3 microM to 10 microM). 2. ATP induced a transient increase in the
      intracellular calcium concentration ([Ca2+]i) in a concentration-dependent manner
      which was very similar to the ATP-evoked plasminogen release, whereas glutamate
      (100 microM) had no effect on [Ca2+]i (70 out of 70 cells) in microglial cells. A
      second application of ATP (100 microM) stimulated an increase in [Ca2+]i similar
      to that of the first application (21 out of 21 cells). 3. The ATP-evoked increase
      in [Ca2+]i was totally dependent on extracellular Ca2+, 2-Methylthio ATP was
      active (7 out of 7 cells), but alpha,beta-methylene ATP was inactive (7 out of 7
      cells) at inducing an increase in [Ca2+]i. Suramin (100 microM) was shown not to
      inhibit the ATP-evoked increase in [Ca2+]i (20 out of 20 cells). 2'- and 3'-O-(4
      Benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), a selective agonist of P2X7
      receptors, evoked a long-lasting increase in [Ca2+]i even at 1 microM, a
      concentration at which ATP did not evoke the increase. One hour pretreatment with
      adenosine 5'-triphosphate-2', 3'-dialdehyde (oxidized ATP, 100 microM), a
      selective antagonist of P2X7 receptors, blocked the increase in [Ca2+]i induced
      by ATP (10 and 100 microM). 4. These data suggest that ATP may transit
      information from neurones to microglia, resulting in an increase in [Ca2+]i via
      the ionotropic P2X7 receptor which stimulates the release of plasminogen from the
      microglia.

PMID- 9579724
TI  - Opposite effects of nitric oxide donors on DNA single strand breakage and
      cytotoxicity caused by tert-butylhydroperoxide.
AB  - 1. The effects of three different NO donors on tert-butylhydroperoxide (tB-OOH)
      induced DNA cleavage and toxicity were investigated in U937 cells. 2. Treatment
      with S-nitroso-N-acetyl-penicillamine (SNAP, 1-30 microM), while not in itself
      DNA-damaging, potentiated the DNA strand scission induced by 200 microM tB-OOH in
      a concentration-dependent fashion. The enhancing effects of SNAP were observed
      with two different techniques for the assessment of DNA damage. Decomposed SNAP
      was inactive. S-nitrosoglutathione (GSNO, 300 microM) and (Z)-1-[(2-aminoethyl)-N
      (2-ammonioethyl) amino]diazen-1-ium-1,2-diolate (DETA-NO, 1 mM) also increased
      DNA cleavage generated by tB-OOH and these responses, as well as that mediated by
      SNAP, were prevented by the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazolin-1
      oxyl-3-oxide (PTIO). 3. SNAP neither inhibited catalase activity nor increased
      the formation of DNA lesions in cells exposed to H2O2. Furthermore, SNAP did not
      affect the rate of rejoining of the DNA single strand breaks generated by tB-OOH.
      4. Under the conditions utilized in the DNA damage experiments, treatment with tB
      OOH alone or associated with SNAP did not cause cell death. However, SNAP as well
      as GSNO markedly reduced the lethal response promoted by millimolar
      concentrations of tB-OOH and these effects were abolished by PTIO. Decomposed
      SNAP was inactive. 5. It is concluded that low levels of NO donors, which
      probably release physiological concentrations of NO, enhance the accumulation of
      DNA single strand breaks in U937 cells exposed to tB-OOH. This NO-mediated effect
      appears to (a) not depend on inhibition of either DNA repair (which would
      increase the net accumulation of DNA lesions by preventing DNA single strand
      break removal) or catalase activity (which would also enhance the net
      accumulation of DNA lesions since H2O2 is one of the species mediating the tB-OOH
      induced DNA cleavage) and (b) be caused by enforced formation of tB-OOH-derived
      DNA-damaging species. In contrast to these results, similar concentrations of NO
      prevented cell death caused by millimolar concentrations of tB-OOH. Hence, DNA
      single strand breakage generated by tB-OOH in the absence or presence of NO does
      not represent a lethal event.

PMID- 9579725
TI  - Characterization of the recombinant human prostanoid DP receptor and
      identification of L-644,698, a novel selective DP agonist.
AB  - 1. A human embryonic kidney cell line [HEK 293(EBNA)] stably expressing the human
      recombinant prostaglandin D2 (PGD2) receptor (hDP) has been characterized with
      respect to radioligand binding and signal transduction properties by use of
      prostanoids and prostanoid analogues. Radioligand binding studies included
      saturation analyses, the effects of nucleotide analogues, the initial rate of
      ligand-receptor association and equilibrium competition assays. In addition,
      adenosine 3':5'-cyclic monophosphate (cyclic AMP) generation in response to
      ligand challenge was also measured, as this is the predominant hDP signalling
      pathway. 2. L-644,698 ((4-(3-(3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl) propyl)
      benzoic acid) (racemate)) was identified as a novel ligand having high affinity
      for hDP with an inhibitor constant (Ki) of 0.9 nM. This Ki value was comparable
      to the Ki values obtained in this study for ligands that have previously shown
      high affinity for DP: PGD2 (0.6 nM), ZK 110841 (0.3 nM), BW245C (0.4 nM), and BW
      A868C (2.3 nM). 3. L-644,698 was found to be a full agonist with an EC50 value of
      0.5 nM in generating cyclic AMP following activation of hDP. L-644,698 is,
      therefore, comparable to those agonists with known efficacy at the DP receptor
      (EC50): PGD2 (0.5 nM), ZK 110841 (0.2 nM) and BW245C (0.3 nM). 4. L-644,698
      displayed a high degree of selectivity for hDP when compared to the family of
      cloned human prostanoid receptors: EP1 (> 25,400 fold), EP2 (approximately 300
      fold), EP3-III (approximately 4100 fold), EP4 (approximately 10000 fold), FP (>
      25,400 fold), IP (> 25,400 fold) and TP (> 25,400 fold). L-644,698 is, therefore,
      one of the most selective DP agonists as yet described. 5. PGJ2 and delta12-PGJ2,
      two endogenous metabolites of PGD2, were also tested in this system and shown to
      be effective agonists with Ki and EC50 values in the nanomolar range for both
      compounds. In particular, PGJ2 was equipotent to known DP specific agonists with
      a Ki value of 0.9 nM and an EC50 value of 1.2 nM.

PMID- 9579726
TI  - Evidence that inducible nitric oxide synthase is involved in LPS-induced plasma
      leakage in rat skin through the activation of nuclear factor-kappaB.
AB  - 1. Rats challenged with lipopolysaccharide (LPS) produce large amounts of nitric
      oxide (NO) following the induction of the inducible NO-synthase (iNOS) in several
      tissues and organs. Recent studies have shown that the expression of iNOS is
      regulated at the transcriptional level by a transcription nuclear factor-kappaB
      (NF-kappaB). In this study we investigated the role of NO in a model of LPS
      induced plasma-leakage in rat skin and the involvement of NF-kappaB. 2. Plasma
      leakage in the rat skin was measured over a period of 30 min to 2 h as the local
      accumulation of intravenous (i.v.) injection of [125I]-human serum albumin
      ([125I]-HSA) in response to intradermal (i.d.) injection of LPS. LPS (1, 10, 100
      microg/site) produced a dose-related increase in plasma extravasation (18.2+/
      3.2, 27.2+/-2.9, 40.4+/-9.6 microl/site) as compared to saline control (11.4+/
      2.2 microl/site). This increase was maximal after 2 h; therefore this time point
      and the dose of LPS 10 microg/site was used in all the successive experiments. 3.
      To investigate the role of NO in LPS-induced plasma leakage in rat skin, the non
      selective NOS inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the more
      selective iNOS inhibitor S-methyl-isothiourea (SMT) was injected i.d. with LPS. L
      NAME and SMT (0.01, 0.1 and 1 micromol/site) inhibited LPS-induced plasma leakage
      in a dose-related fashion (L-NAME: 26.0+/-5.5, 20.2+/-1.6, 18.0+/-2.0
      microl/site; SMT: 19.5+/-1.5, 17.0+/-1.6, 15.0+/-2.6 microl/site) as compared to
      LPS alone (27.2+/-2.9 microl/site). At the lowest concentration used (0.01
      micromol/site), SMT significantly reduced plasma leakage by 30%+/-0.7 while L
      NAME (0.01 micromol/site) was not effective. 4. Treatment with increasing
      concentrations of pyrrolidinedithyocarbamate (PDTC) (0.01, 0.1, 1 micromol/site),
      an inhibitor of NF-kappaB activation, injected i.d. 30 min before LPS challenge,
      inhibited in a concentration-dependent fashion LPS-induced plasma leakage by
      9.0+/-0.6, 33+/-4.0, 51+/-2.0% respectively. Moreover, PDTC (0.1, 1
      micromol/site) suppressed LPS-induced NF-kappaB DNA-binding. 5. Western blot
      analysis showed significant levels of iNOS proteins in the skin samples of LPS
      treated rats, as compared to basal levels present in saline-injected rat skin.
      PDTC (0.1, 1.0 micromol/site) dose-dependently decreased the amount of iNOS
      protein expression induced by LPS. 6. Our results indicate that LPS-induced
      plasma leakage in rat skin is modulated by NO mainly produced by the inducible
      isoform of NOS. Furthermore, the suppression of plasma leakage by PDTC, an
      inhibitor of NF-kappaB activation, is correlated to the inhibition of iNOS
      protein expression.

PMID- 9579727
TI  - Antidepressant-like effects of endogenous histamine and of two histamine H1
      receptor agonists in the mouse forced swim test.
AB  - 1. Effects of substances which are able to alter brain histamine levels and two
      histamine H1 receptor agonists were investigated in mice by means of an animal
      model of depression, the forced swim test. 2. Imipramine (10 and 30 mg kg(-1),
      i.p.) and amitriptyline (5 and 15 mg kg(-1), i.p.) were used as positive
      controls. Their effects were not affected by pretreatment with the histamine H3
      receptor agonist, (R)-alpha-methylhistamine, at a dose (10 mg kg(-1), i.p.) which
      did not modify the cumulative time of immobility. 3. The histamine H3 receptor
      antagonist, thioperamide (2-20 mg kg(-1), s.c.), showed an antidepressant-like
      effect, with a maximum at the dose of 5 mg kg(-1), which was completely prevented
      by (R)-alpha-methylhistamine. 4. The histamine-N-methyltransferase inhibitor,
      metoprine (2-20 mg kg(-1), s.c.), was effective with an ED50 of 4.02 (2.71-5.96)
      mg kg(-1); its effect was prevented by (R)-alpha-methylhistamine. 5. The
      histamine precursor, L-histidine (100-1000 mg kg(-1), i.p.), dose-dependently
      decreased the time of immobility [ED30 587 (499-712) mg kg(-1)]. The effect of
      500 mg kg(-1) L-histidine was completely prevented by the selective histidine
      decarboxylase inhibitor, (S)-alpha-fluoromethylhistidine (50 mg kg(-1), i.p.),
      administered 15 h before. 6. The highly selective histamine H1 receptor agonist,
      2-(3-trifluoromethylphenyl)histamine (0.3-6.5 microg per mouse, i.c.v.), and the
      better known H1 agonist, 2-thiazolylethylamine (0.1-1 microg per mouse, i.c.v.),
      were both dose-dependently effective in decreasing the time of immobility [ED50
      3.6 (1.53-8.48) and 1.34 (0.084-21.5) microg per mouse, respectively]. 7. None of
      the substances tested affected mouse performance in the rota rod test at the
      doses used in the forced swim test. 8. It was concluded that endogenous histamine
      reduces the time of immobility in this test, suggesting an antidepressant-like
      effect, via activation of H1 receptors.

PMID- 9579728
TI  - Involvement of bradykinin B1 and B2 receptors in relaxation of mouse isolated
      trachea.
AB  - 1. The aim of the present study was to investigate the effects of bradykinin and
      [des-Arg9]-bradykinin and their relaxant mechanisms in the mouse isolated
      trachea. 2. In the resting tracheal preparations with intact epithelium,
      bradykinin and [des-Arg9]-bradykinin (each drug, 0.01-10 microM) induced neither
      contraction nor relaxation. In contrast, bradykinin (0.01-10 microM) induced
      concentration-dependent relaxation when the tracheal preparations were
      precontracted with methacholine (1 microM). The relaxation induced by bradykinin
      was inhibited by the B2 receptor antagonist, D-Arg0-[Hyp3,Thi5,D-Tic7,Oic8]
      bradykinin (Hoe 140, 0.01-1 microM) in a concentration-dependent manner whereas
      the B1 receptor antagonist, [des-Arg9,Leu8]-bradykinin (0.01-1 microM), had no
      inhibitory effect on bradykinin-induced relaxation. [des-Arg9]-bradykinin (0.01
      10 microM) also caused concentration-dependent relaxation after precontraction
      with methacholine. The relaxation induced by [des-Arg9-bradykinin was
      concentration-dependently inhibited by the B1 receptor antagonist, [des
      Arg9,Leu8]-bradykinin (0.01-1 microM), whereas the B2 receptor antagonist, Hoe
      140 (0.01-1 microM) was without effect. 3. In the presence of the cyclo-oxygenase
      inhibitor, indomethacin (0.01-1 microM), the relaxations induced by bradykinin
      and [des-Arg9]-bradykinin were inhibited concentration-dependently. 4. Two nitric
      oxide (NO) biosynthesis inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 100
      microM) and NG-nitro-L-arginine (L-NOARG, 100 microM) had no inhibitory effects
      on the relaxations induced by bradykinin and [des-Arg9]-bradykinin. Neither did
      the selective inhibitor of the soluble guanylate cyclase, 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) inhibit the relaxations
      induced by bradykinin and [des-Arg9]-bradykinin. 5. Prostaglandin E2 (PGE2, 0.01
      33 microM) caused concentration-dependent relaxation of the tracheal preparations
      precontracted with methacholine. Indomethacin (1 microM) and ODQ (10 microM)
      exerted no inhibitory effects on the relaxation induced by PGE2. 6. The NO-donor,
      sodium nitroprusside (SNP; 0.01-100 microM) also caused concentration-dependent
      relaxation of the tracheal preparations precontracted with methacholine. ODQ (0.1
      1 microM) concentration-dependently inhibited the relaxation induced by SNP. 7.
      These data demonstrate that bradykinin and [des-Arg9]-bradykinin relax the mouse
      trachea precontracted with methacholine by the activation of bradykinin B2
      receptors and B1-receptors, respectively. The stimulation of bradykinin receptors
      induces activation of the cyclo-oxygenase pathway, leading to the production of
      relaxing prostaglandins. The NO pathway is not involved in the bradykinin-induced
      relaxation. The relaxation caused by NO-donors in the mouse trachea is likely to
      be mediated via activation of soluble guanylate cyclase.

PMID- 9579729
TI  - Heterogeneity and underlying mechanism for inotropic action of endothelin-1 in
      rat ventricular myocytes.
AB  - 1. To clarify the mechanisms underlying the positive inotropic action of
      endothelin-1 (ET-1), we investigated the effect of ET-1 on twitch cell shortening
      and the Ca2+ transient in rat isolated ventricular myocytes loaded with a
      fluorescent Ca2+ indicator indo-1. 2. There was a cell-to-cell heterogeneity in
      response to ET-1. ET-1 (100 nM) increased twitch cell shortening in only 6 of 14
      cells (44%) and the increase in twitch cell shortening was always accompanied by
      an increase in the amplitude of the Ca2+ transient. 3. The ET(A)- and ET(B)
      receptors antagonist TAK-044 (100 nM) almost reversed both the ET-1-induced
      increases in twitch cell shortening and in the Ca2+ transient. In the ET-1 non
      responding cells, the amplitude of the Ca2+ transient never increased. 4.
      Intracellular pH slightly increased (approximately 0.08 unit) after 30 min
      perfusion of ET-1 in rat ventricular myocytes. However, ET-1 did not change the
      myofilament responsiveness to Ca2+, which was assessed by (1) the relationship
      between the Ca2+ transient amplitude and twitch cell shortening, and by (2) the
      Ca2+ transient-cell shortening phase plane diagram during negative staircase. 5.
      We concluded that there was a cell-to-cell heterogeneity in the positive
      inotropic effect of ET-1, and that the ET-receptor-mediated positive inotropic
      effect was mainly due to an increase in the Ca2+ transient amplitude rather than
      to an increase in myofilament responsiveness to Ca2+.

PMID- 9579730
TI  - Evidence that different mechanisms underlie smooth muscle relaxation to nitric
      oxide and nitric oxide donors in the rabbit isolated carotid artery.
AB  - 1. The endothelium-dependent relaxants acetylcholine (ACh; 0.03-10 microM) and
      A23187 (0.03-10 microM), and nitric oxide (NO), applied either as authentic NO
      (0.01-10 microM) or as the NO donors 3-morpholino-sydnonimine (SIN-1; 0.1-10
      microM) and S-nitroso-N-acetylpenicillamine (SNAP; 0.1-10 microM), each evoked
      concentration-dependent relaxation in phenylephrine stimulated (1-3 microM; mean
      contraction and depolarization, 45.8+/-5.3 mV and 31.5+/-3.3 mN; n=10) segments
      of rabbit isolated carotid artery. In each case, relaxation closely correlated
      with repolarization of the smooth muscle membrane potential and stimulated a
      maximal reversal of around 95% and 98% of the phenylephrine-induced
      depolarization and contraction, respectively. 2. In tissues stimulated with 30 mM
      KCl rather than phenylephrine, smooth muscle hyperpolarization and relaxation to
      ACh, A23187, authentic NO and the NO donors were dissociated. Whereas the
      hyperpolarization was reduced by 75-80% to around a total of 10 mV, relaxation
      was only inhibited by 35% (n=4-7 in each case; P<0.01). The responses which
      persisted to ACh and A23187 in the presence of 30 mM KCl were abolished by either
      the NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME; 100 microM) or
      the inhibitor of soluble guanylyl cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1
      one (ODQ; 10 microM; 10 min; n=4 in each case; P<0.01). 3. Exposure to ODQ
      significantly attenuated both repolarization and relaxation to ACh, A23187 and
      authentic NO, reducing the maximum changes in both membrane potential and tension
      to each relaxant to around 60% of control values (n=4 in each case; P<0.01). In
      contrast, ODQ almost completely inhibited repolarization and relaxation to SIN-1
      and SNAP, reducing the maximum responses to around 8% in each case (n=3-5;
      P<0.01). 4. The potassium channel blockers glibenclamide (10 microM), iberiotoxin
      (100 nM) and apamin (50 nM), alone or in combination, had no significant effect
      on relaxation to ACh, A23187, authentic NO, or the NO donors SIN-1 and SNAP (n=4
      in each case; P>0.05). Charybdotoxin (ChTX; 50 nM) almost abolished
      repolarization to ACh (n=4; P<0.01) and inhibited the maximum relaxation to ACh,
      A23187 and authentic NO each by 30% (n=4-8; P<0.01). Application of ODQ (10
      microM; 10 min) abolished the ChTX-insensitive responses to ACh, A23187 and
      authentic NO (n=4 in each case; P<0.01 5. When the concentration of phenylephrine
      was reduced (to 0.3-0.5 microM) to ensure the level of smooth muscle contraction
      was the same as in the absence of potassium channel blocker, ChTX had no effect
      on the subsequent relaxation to SIN-1 (n=4; P>0.05). However, in the presence of
      tone induced by 1-3 microM phenylephrine (51.2+/-3.3 mN; n=4), ChTX significantly
      reduced relaxation to SIN-1 by nearly 50% (maximum relaxation 53.2+/-6.3%, n=4;
      P<0.01). 6. These data indicate that NO-evoked relaxation of the rabbit isolated
      carotid artery can be mediated by three distinct mechanisms: (a) a cyclic GMP
      dependent, voltage-independent pathway, (b) cyclic GMP-mediated smooth muscle
      repolarization and (c) cyclic GMP-independent, ChTX-sensitive smooth muscle
      repolarization. Relaxation and repolarization to both authentic and endothelium
      derived NO in this large conduit artery appear to be mediated by parallel cyclic
      GMP-dependent and -independent pathways. In contrast, relaxation to the NO-donors
      SIN-1 and SNAP appears to be mediated entirely via cyclic GMP-dependent
      mechanisms.

PMID- 9579731
TI  - Alpha1L-adrenoceptor mediation of smooth muscle contraction in rabbit bladder
      neck: a model for lower urinary tract tissues of man.
AB  - 1. The alpha1-adrenoceptor population mediating contractile responses to
      noradrenaline (NA) in smooth muscles of the bladder neck from rabbit (RBN) has
      been characterized by use of quantitative receptor pharmacology. 2. Experiments
      with several 'key' alpha1-adrenoceptor antagonists of varying subtype
      selectivities (RS-17053, BMY 7378, indoramin, 5-methylurapidil, prazosin, REC
      15/2739, SNAP 5089, terazosin, WB 4101, tamsulosin, (+)-cyclazosin and RS-100329)
      were conducted. Schild regression analyses yielded affinity (mean pKb) estimates
      of 7.1, 6.2, 8.6, 8.6, 8.4, 9.3, 7.0, 7.4, 8.9, 10.0, 7.1 and 9.3, respectively,
      although deviations from unit Schild regression slope question the robustness of
      data for RS-17053 and SNAP 5089. 3. The nature of antagonism by these agents and
      the profile of affinity determinations generated together suggest that a single
      alpha1-adrenoceptor subtype mediates contractile responses of RBN to NA.
      Additional studies with phenylephrine indicated also an agonist-independence of
      this profile. Pharmacologically, this profile was reminiscent of that described
      as 'alpha1L'-adrenoceptor, which has been shown to mediate contractions of
      several tissues including lower urinary tract (LUT) tissues of man. Furthermore,
      a similarity was noticed between the 'alpha1L'-adrenoceptor described here in RBN
      and the rabbit and human cloned alpha1a-adrenoceptor (based on data from both
      whole cell radioligand binding at 37 degrees C and [3H]-inositol phosphates
      accumulation assays), characterizations of which have been published elsewhere.
      4. In conclusion, the RBN appears to provide a predictive pharmacological assay
      for the study of NA-induced smooth muscle contraction in LUT tissues of man.

PMID- 9579732
TI  - Differential effects of endotoxaemia on pressor and vasoconstrictor actions of
      angiotensin II and arginine vasopressin in conscious rats.
AB  - 1. Regional haemodynamic responses to arginine vasopressin (AVP; 0.5, 1.0, 5.0
      pmol i.v.) and angiotensin II (AII; 5.0, 10.0, 50.0 pmol i.v.) were measured in
      conscious Long Evans rats at various times (0, 2, 6 and 24 h) during infusion of
      lipopolysaccharide (LPS, 150 microg kg(-1) h(-1), i.v., n=9) or saline (n=9).
      Additional experiments were performed in vasopressin-deficient (Brattleboro) rats
      infused with LPS (n=7) or saline (n=8) to determine whether or not, in the
      absence of circulating vasopressin, responses to the exogenous peptides differed
      from those in Long Evans rats. 2. In the Long Evans rats, during the 24 h
      infusion of LPS, there was a changing haemodynamic profile with renal
      vasodilatation from 2 h onwards, additional mesenteric vasodilatation at 6 h, and
      a modest hypotension (reduction in mean arterial blood pressure (MAP) from 103+/
      1 to 98+/-2 mmHg) associated with renal and hindquarters vasodilatation at 24 h.
      3. In the Brattleboro rats, the changes in regional haemodynamics during LPS
      infusion were more profound than in the Long Evans rats. At 2 h and 6 h, there
      was a marked fall in MAP (from 103+/-3 mmHg; to 65+/-3 mmHg at 2 h, and to 82+/-4
      mmHg at 6 h) associated with vasodilatation in all three vascular beds. After 24
      h infusion of LPS, the hypotension was less although still significant (from
      103+/-3 mmHg; to 93+/-4 mmHg, a change of 10+/-4 mmHg), and there was renal and
      hindquarters vasodilatation, but mesenteric vasoconstriction. 4. During infusion
      of LPS, at each time point studied, and in both strains of rat, pressor responses
      to AII and AVP were reduced, but the changes were less marked at 6 h than at 2 h
      or 24 h. The reduced pressor responses were not accompanied by generalized
      reductions in the regional vasoconstrictor responses. Thus, in the Long Evans
      rats, the renal vasoconstrictor responses to both peptides were enhanced (at 6 h
      and 24 h for AVP; at all times for AII), whereas the mesenteric vasoconstrictor
      response to AVP was unchanged at 2 h, enhanced at 6 h and reduced at 24 h. The
      mesenteric vasoconstrictor response to AII was reduced at 2 h, normal at 6 h and
      reduced at 24 h. The small hindquarters vasoconstrictor responses to both
      peptides were reduced at 2 h and 6 h, but normal at 24 h. 5. In the Brattleboro
      rats, the renal vasoconstrictor responses to both peptides were reduced at 2 h
      and enhanced at 6 h and 24 h, whereas the mesenteric vasoconstrictor response to
      AVP was normal at 2 h and 6 h, and reduced at 24 h. The response to AII was
      reduced at 2 h, normal at 6 h and reduced again at 24 h. There were no
      reproducible hindquarters vasoconstrictions to AVP in the Brattleboro rats. The
      small hindquarters vasoconstrictor responses to AII were unchanged at 2 h and
      enhanced at 6 h and 24 h. 6. In isolated perfused mesenteric vascular beds,
      removed after 24 h of LPS infusion in vivo, there was an increase in the potency
      of AVP in both strains (Long Evans, ED50 saline: 56.9+/-15.0 pmol, ED50 LPS:
      20.4+/-4.8 pmol, Brattleboro, ED50 saline: 38.6+/-4.2, ED50 LPS: 19.6+/-2.9
      pmol), but no change in the responses to AII. 7. These findings indicate that a
      reduced pressor response to a vasoconstrictor challenge during LPS infusion is
      not necessarily associated with a reduced regional vasoconstriction. The data
      obtained in the Brattleboro rats indicate a potentially important role for
      vasopressin in maintaining haemodynamic status during LPS infusion in Long Evans
      rats. However, it is unlikely that the responses to exogenous AVP (or AII) are
      influenced by changes in the background level of endogenous vasopressin, since
      the patterns of change were similar in Long Evans and Brattleboro rats. 8. The
      results obtained in isolated perfused mesenteric vascular beds differed from
      those in vivo, possibly due to the conditions pertaining with in vitro perfusion.

PMID- 9579733
TI  - Exogenous NPY modulation of cardiac autonomic reflexes and its pressor effect in
      the conscious rabbit.
AB  - 1. Neuropeptide Y (NPY) may inhibit sympathetic and vagal transmission via
      presynaptic Y2 receptors and cause vasoconstriction via postsynaptic Y1
      receptors. We examined the effects of NPY and related peptides on cardiovascular
      parameters and autonomic reflexes in the conscious rabbit. Further, the
      postjunctional effects of NPY and related peptides were assessed on acetylcholine
      (ACh) and isoprenaline agonist dose-chronotropic response curves. 2. In conscious
      rabbits the cardiac baroreceptor-heart rate reflex (baroreflex), Bezold-Jarisch
      like and nasopharyngeal reflexes were assessed in control, propranolol-treated or
      methscopolamine-treated (baroreflex only) groups, before and 30 min after i.v.
      administration of NPY (10 microg kg[-1] + 5 microg kg[-1] min[-1]) or vehicle
      (saline, 10 ml h[-1]). The effects of equivalent pressor doses of [Leu31,
      Pro34]NPY or methoxamine on the baroreflex were also examined. In separate
      animals, dose-heart rate (HR) response curves to isoprenaline or ACh were
      constructed before and 15 min after administration of NPY, [Leu31,Pro34]NPY (ACh
      only) or [Leu31,Pro34]NpY + sodium nitroprusside (ACh only). 3. Administration of
      NPY-receptor agonists caused sustained bradycardia (in the absence of
      methscopolamine) and rightward shifts of the barocurves in all 3 groups. The
      range of sympathetically-mediated tachycardia was significantly decreased by NPY
      or [Leu31,Pro34]NPY in the methscopolamine-treated group. However, these changes
      in the baroreflex were no different from those elicted by equipressor doses of
      methoxamine. There was no vagal inhibition by any NPY-receptor agonist in all
      three autonomic reflexes examined. ACh or isoprenaline dose-HR response curves
      were not affected by NPY peptide administration. 4. We conclude that in the
      conscious rabbit, at a single dose that elicits a significant pressor response,
      exogenous NPY has no direct effect on modulation of cardiac and autonomic
      reflexes. Non-specific effects of exogenous NPY on the baroreflex may be fully
      explained by its pressor action. There was no effect of NPY on postjunctional ACh
      or isoprenaline agonist dose-response curves. Therefore, it is unlikely that
      endogenous NPY has a functional role in directly modulating cardiac autonomic
      neurotransmission in the rabbit.

PMID- 9579734
TI  - Evidence for the existence of [3H]-trimetazidine binding sites involved in the
      regulation of the mitochondrial permeability transition pore.
AB  - 1. Trimetazidine is an anti-ischaemic drug effective in different experimental
      models but its mechanism of action is not fully understood. Data indicate that
      mitochondria could be the main target of this drug. The aim of this work was to
      investigate the binding of [3H]-trimetazidine on a purified preparation of rat
      liver mitochondria. 2. [3H]-trimetazidine binds to two populations of
      mitochondrial binding sites with Kd values of 0.96 and 84 microM. The total
      concentration of binding sites is 113 pmol mg(-1) protein. Trimetazidine binding
      sites are differently distributed. The high-affinity ones are located on the
      outer membranes and represent only a small part (4%) of total binding sites,
      whereas the low-affinity ones are located on the inner membranes and are more
      abundant (96%) with a Bmax=108 pmol mg(-1) protein. 3. Drug displacement studies
      with pharmacological markers for different mitochondrial targets showed that [3H]
      trimetazidine binding sites are different from previously described mitochondrial
      sites. 4. The possible involvement of [3H]-trimetazidine binding sites in the
      regulation of the mitochondrial permeability transition pore (MTP), a voltage
      dependent channel sensitive to cyclosporin A, was investigated with mitochondrial
      swelling experiments. Trimetazidine inhibited the mitochondrial swelling induced
      by Ca2+ plus tert-butylhydroperoxide (t-BH). This effect was concentration
      dependent with an IC50 value of 200 microM. 5. Assuming that trimetazidine
      effectiveness may be related to its structure as an amphiphilic cation, we
      compared it with other compounds exhibiting the same chemical characteristic both
      for their ability to inhibit MTP opening and to displace [3H]-trimetazidine bound
      to mitochondria. Selected compounds were drugs known to interact with various
      biological membranes. 6. A strong correlation between swelling inhibition potency
      and low-affinity [3H]-trimetazidine binding sites was observed: r=0.907 (n=24;
      P<0.001). 7. These data suggest that mitochondrial sites labelled with [3H]
      trimetazidine may be involved in the MTP inhibiton.

PMID- 9579735
TI  - Binding of K(ATP) channel modulators in rat cardiac membranes.
AB  - 1. The binding of [3H]-P1075, a potent opener of adenosine-5'-triphosphate-(ATP)
      sensitive K+ channels, was studied in a crude heart membrane preparation of the
      rat, at 37 degrees C. 2. Binding required MgATP. In the presence of an ATP
      regenerating system, MgATP supported [3H]-P1075 binding with an EC50 value of 100
      microM and a Hill coefficient of 1.4. 3. In saturation experiments [3H]-P1075
      binding was homogeneous with a KD value of 6+/-1 nM and a binding capacity (Bmax)
      of 33+/-3 fmol mg(-1) protein. 4. Upon addition of an excess of unlabelled P1075,
      the [3H]-P1075-receptor complex dissociated in a mono-exponential manner with a
      dissociation rate constant of 0.13+/-0.01 min(-1). If a bi-molecular association
      mechanism was assumed, the dependence of the association kinetics on label
      concentration gave an association rate constant of 0.030+/-0.003 nM(-1) min(-1).
      From the kinetic experiments the KD value was calculated as 4.7+/-0.6 nM. 5.
      Openers of the ATP-sensitive K+ channel belonging to different structural classes
      inhibited specific [3H]-P1075 binding in a monophasic manner to completion; an
      exception was minoxidil sulphate where maximum inhibition was 68%. The potencies
      of the openers in this assay agree with published values obtained in rat
      cardiocytes and are on average 3.5 times lower than those determined in rat
      aorta. 6. Sulphonylureas, such as glibenclamide and glibornuride and the
      sulphonylurea-related carboxylate, AZ-DF 265, inhibited [3H]-P1075 binding with
      biphasic inhibition curves. The high affinity component comprised about 60% of
      the curves with the IC50 value of glibenclamide being approximately 90 nM;
      affinities for the low affinity component were in the microM concentration range.
      The fluorescein derivative, phloxine B, showed a monophasic inhibition curve with
      an IC50 value of 6 microM, a maximum inhibition of 94% and a Hill coefficient of
      1.5. 7. It is concluded that binding studies with [3H]-P1075 are feasible in rat
      heart membranes in the presence of MgATP and of an ATP-regenerating system. The
      pharmacological profile of the [3H]-P1075 binding sites in the cardiac
      preparation, which probably contains sulphonylurea receptors (SURs) from cardiac
      myocytes (SUR2A) and vascular smooth muscle cells (SUR2B), differs from that
      expected for SUR2A and SUR2B.

PMID- 9579736
TI  - Enhanced involvement of endothelin in the haemodynamic sequelae of endotoxaemia
      in conscious, hypertensive, transgenic ((mRen-2)27) rats.
AB  - 1. Age-matched (3-4 months old) male, heterozygous, hypertensive, transgenic
      ((mRen-2)27) rats (abbreviated to TG rats) and the normotensive control animals
      (homozygous, Hannover Sprague-Dawley rats (abbreviated to SD rats), were
      chronically instrumented for the assessment of regional haemodynamic responses to
      continuous lipopolysaccharide (LPS) infusion (150 microg kg(-1) h(-1), i.v.) 2.
      The early (1-2 h) hypotension in SD rats (-11+/-3 mmHg; n=7) was significantly
      less than that in TG rats (-35+/-3 mmHg; n=8), but by 24 h mean arterial blood
      pressure (MAP) in both strains of rat was not different from the pre-LPS value
      (SD rats: baseline, 108+/-3 mmHg; 24 h LPS, 112+/-4 mmHg; TG rats: baseline,
      171+/-2 mmHg; 24 h LPS, 169+/-3 mmHg). At this stage in the SD rats there was a
      renal vasodilatation (delta vascular conductance, 29+/-10 [kHz mmHg(-1)]10(3))
      but not in TG rats (delta vascular conductance 2+/-3[kHz mmHg(-1)]10(3)). 3. Co
      infusion of LPS and the non-selective endothelin receptor antagonist, SB 209670
      (600 microg kg(-1) bolus, 600 microg kg(-1) h(-1)) between 24 and 31 h in SD rats
      caused a fall in MAP of 16+/-2 mmHg accompanied by hindquarters vasodilatation
      (delta vascular conductance 11+/-3 (kHz mmHg(-1))10(3)). In TG rats, under the
      same conditions, the fall in MAP was -60+/-6 mmHg, and there were renal,
      mesenteric and hindquarters vasodilatations (delta vascular conductance, 23+/-5,
      32+/-7, and 14+/-4 (kHz mmHg(-1))10(3), respectively). All effects, except the
      hindquarters vasodilatation, were greater in TG than in SD rats. 4. In TG rats
      infused with LPS alone for 31 h, between 24 and 31 h the fall in MAP was -17+/-4
      mmHg, and the changes in renal, mesenteric and hindquarters vascular conductances
      were 5+/-3, -4+/-5, and 12+/-4 (kHz mmHg(-1)10(3), respectively. 5.
      Administration of the angiotensin (AT1)-receptor antagonist, losartan (10 mg kg(
      1), i.v.) following co-infusion of LPS and SB 209670 between 24 and 31 h caused
      similar falls in MAP in SD and TG rats (-12+/-3 and -14+/-4 mmHg, respectively).
      6. These results, together with previous findings, are consistent with a relative
      enhancement of the contribution of endothelin to the maintenance of
      cardiovascular status in endotoxaemic TG rats, particularly through a mesenteric
      vasoconstrictor action.

PMID- 9579737
TI  - The protective effects of CP-060S on ischaemia- and reperfusion- induced
      arrhythmias in anaesthetized rats.
AB  - 1. CP-060S is a novel sodium and calcium overload inhibitor, and is also
      characterized as a calcium channel blocker. As these activities have each been
      shown independently to ameliorate ischaemia damage in the myocardium, the
      combination may synergistically exert cardioprotection. In this study, therefore,
      the protective effect of CP-060S against ischaemia- and reperfusion-induced
      arrhythmia was evaluated in anesthetized rats. 2. Rats were anaesthetized with
      pentobarbitone, and the left anterior descending coronary artery was occluded for
      either 5 min with subsequent reperfusion (a reperfusion-induced arrhythmia model)
      or 30 min without (an ischaemia-induced arrhythmia model). All drugs were
      intravenously administered 1 min before the onset of occlusion. 3. In the
      reperfusion-induced arrhythmia model, the animals in the vehicle-treated group
      exhibited ventricular tachycardia (VT) in 100%, ventricular fibrillation (VF) in
      89%, and death caused by sustained VF in 56%. CP-060S (30-300 microg kg(-1)) dose
      dependently suppressed the incidences of arrhythmias. Significant decreases
      occurred at 100 microg kg(-1) in VF (incidence: 42%) and mortality (8%), and at
      300 microg kg(-1) in VT (50%), VF (33%) and mortality (8%). This protective
      effect of CP-060S was 10 times more potent than that of a pure calcium channel
      blocker, diltiazem (30-1000 microg kg(-1)) we tested, in terms of effective dose
      ranges. As both drugs decreased myocardial oxygen consumption estimated by rate
      pressure product to a similar extent, the calcium channel blocking activity of CP
      060S would not seem to be sufficient to explain its potency. 4. In the same
      model, co-administration of ineffective doses of diltiazem (300 microg kg(-1))
      and a sodium and calcium overload inhibitor, R56865 (100 microg kg(-1)), produced
      significant suppression of VT (incidence: 62%), VF (46%) and mortality (8%). By
      contrast, co-administration of R56865 at the same dose with CP-060S (300 microg
      kg(-1)) did not add to the effect of a single treatment of CP-060S. 5. In the
      ischaemia-induced arrhythmia model, CP-060S (300 microg kg(-1)) significantly
      decreased the incidence of VF from 75% to 29%, whereas diltiazem (1 mg kg(-1))
      was ineffective. 6. These results suggest that CP-060S inhibits both ischaemia-
      and reperfusion-induced arrhythmia. The combination of the calcium channel
      blocking effect and the calcium overload inhibition was hypothesized to
      contribute to these potently protective effects.

PMID- 9579738
TI  - Acetylcholine sensitivity of biphasic Ca2+ mobilization induced by nicotinic
      receptor activation at the mouse skeletal muscle endplate.
AB  - 1. Acetylcholine (ACh) was locally applied onto the endplate region in a mouse
      phrenic nerve-diaphragm muscle preparation to measure intracellular free calcium
      ([Ca2+]i) entry through nicotinic ACh receptors (AChRs) by use of Ca2+-aequorin
      luminescence. 2. ACh (0.1-3 mM, 20 microl) elicited biphasic elevation of [Ca2+]i
      (fast and slow Ca2+ mobilization) in muscle cells. The peak amplitude of the slow
      Ca2+ mobilization (not accompanied by twitch tension) was concentration
      dependently increased by ACh, whereas that of the fast component (accompanied by
      twitch tension) reached a maximum response at a lower concentration (0.1 mM) of
      applied ACh. 3. A pulse of nicotinic agonists, (-)-nicotine (10 mM) and 1,1
      dimethyl-4-phenyl-piperazinium (10 mM), but not a muscarinic agonist pilocarpine
      (10 mM), also elicited a biphasic Ca2+ signal. 4. Even though ACh release from
      motor nerve endings was blocked by botulinum toxin (5 microg, bolus i.p. before
      isolation of the tissue), the generation of both a fast and slow Ca2+ component
      caused by ACh application was observed. 5. These results strongly suggest that
      ACh locally applied onto the endplate region of skeletal muscle induces a slow
      Ca2+ signal reflecting Ca2+ entry through a postsynaptic nicotinic AChR, which
      has a low sensitivity to transmitter ACh.

PMID- 9579739
TI  - Validation of Furchgott's method to determine agonist-dependent A1-adenosine
      receptor reserve in guinea-pig atrium.
AB  - 1. The ubiquitous distribution of A1-adenosine receptors (A1AdoR) represents an
      impediment to achieve organ and/or response selectivity of A1AdoR agonists.
      Differential receptor reserve may be exploited to overcome this problem. We
      hypothesize that A1AdoR reserve is agonist-dependent and can be accurately
      estimated with Furchgott's method. 2. Concentration-response curves were
      constructed from measurement of the atrial monophasic action potential duration
      in guinea-pig, isolated hearts treated with R(-) N6-(2-phenylisopropyl)adenosine
      (R-PIA) or 2-chloro-N6-cyclopentyl-adenosine (CCPA) before and after treatment
      with the selective, irreversible A1AdoR antagonist 8-cyclopentyl-3-[3-[[4
      (fluorosulphonyl)benzoyl]oxy]propyl]-1-prop ylxanthine (FSCPX). Using Furchgott's
      method, we determined the equilibrium dissociation constant (KA) of R-PIA and
      CCPA, and the fraction of non-inactivated A1AdoRs remaining after FSCPX treatment
      (q(functional)). Values of q(functional) were correlated to the fraction of
      specific binding sites after FSCPX treatment labelled by [3H]-8-cyclopentyl-1,3
      dipropylxanthine ([3H]-CPX) derived from saturation binding normalized to control
      (q(binding)). 3. Both R-PIA and CCPA are full A1AdoR agonists, but have
      significantly different potencies (pD2 [EC50]=6.84+/-0.04 [145 nM] vs 7.36+/-0.04
      [44 nM], respectively), receptor affinities (pKA [KA]= 6.54+/-0.10 [288 nM] vs
      6.13+/-0.03 [734 nM]), and pharmacological shift ratios defined as KA/EC50 (2.2+/
      0.6 vs 15.9+/-1.5). Values for q(functional) and q(binding) were highly
      correlated (r2=0.96). The ratio between the intrinsic efficacies of CCPA and R
      PIA derived from Furchgott's analysis was 5.9, a value similar to the ratio of
      6.2-6.6 calculated from previously obtained binding data. 4. Radioligand binding
      studies validated the use of Furchgott's method to estimate A1AdoR reserve.
      A1AdoR reserve was agonist-dependent. CCPA was shown to be a high intrinsic
      efficacy, low affinity agonist, whereas R-PIA was found to be a low intrinsic
      efficacy, high affinity agonist.

PMID- 9579740
TI  - Dual endothelium-dependent vascular activities of proteinase-activated receptor-2
      activating peptides: evidence for receptor heterogeneity.
AB  - 1. The vascular actions of the proteinase-activated receptor-2-activating
      peptides (PAR2APs), SLIGRL-NH2 (SL-NH2) and SLIGKV-NH2 (KV-NH2) as well as the
      reverse-sequence peptide, LSIGRL-NH2 (LS-NH2) and an N-acylated PAR2AP
      derivative, trans-cinnamoyl-LIGRLO-NH2 (tcLI-NH2), were studied in rat intact and
      endothelium-denuded artery ring preparations, primarily from the pulmonary artery
      (RPA). 2. In RPA rings with but not without a functional endothelium, SL-NH2 (but
      not LS-NH2) caused either an endothelium-dependent relaxation (at concentrations:
      < 10 microM) or (at higher concentrations: > 10 microM), an endothelium-dependent
      contraction. No contractile response was observed in endothelium-denuded
      preparations, that otherwise contracted in response to the PAR1AP, TFLLR-NH2. 3.
      The endothelium-dependent contractile response to SL-NH2 was not blocked by the
      alpha-adrenoceptor antagonist prazosin, the endothelin antagonist BQ123, the
      angiotensin II antagonist DuP753, by tetrodotoxin; nor by the enzyme inhibitors,
      N(omega)-nitro-L-arginine-methylester (NO-synthase), indomethacin (cyclo
      oxygenase), SKF-525A (epoxygenase) and MK886 (leukotriene synthesis inhibitor).
      4. In the relaxation assay, KV-NH2 was 5 fold less potent than SL-NH2, whereas in
      the contractile assay KV-NH2 was about equipotent with SL-NH2. However, the
      maximal contractile response to KV-NH2 was lower than that of SL-NH2. 5. The
      PAR2AP analogue, tcLI-NH2, was as active as SL-NH2 in the relaxation assay but
      was inactive as a contractile agonist in the endothelium-intact RPA. 6. The
      relaxant responses caused by SL-NH2 and trypsin, as well as the contractile
      response caused by SL-NH2, did not desensitize in the course of repeated
      exposures of the tissue to agonist; whereas the contractile response to trypsin,
      only observed at concentrations greater than 30 u ml(-1), was desensitized by
      previous exposure of the tissue to either thrombin or trypsin. 7. In a
      contractile assay, where the tissue was desensitized to a concentration of
      trypsin that would otherwise cause a relaxant response, the preparation still
      contracted in response to SL-NH2. However, the trypsin-desensitized preparations
      were no longer contracted by thrombin. 8. From the cross-desensitization by
      thrombin of the contractile response to trypsin (and vice versa), we concluded
      that the contractile effect of trypsin was due to activation of the thrombin
      receptor and not PAR2. 9. We concluded that the endothelium-dependent contraction
      caused by high concentrations of SL-NH2 is due to an as yet unidentified
      contracting factor; whereas the endothelium-dependent relaxation response
      observed at low concentrations of SL-NH2 (< or = 10 microM) is mediated by nitric
      oxide. 10. The distinct structure activity profiles for the contractile response
      (potency of KV-NH2 < or = SL-NH2) compared with the relaxant response (potency of
      KV-NH2 << SL-NH2); the contractile responsiveness to SL-NH2 of an endothelium
      intact RPA preparation, that did not contract in response to trypsin; and the
      lack of contractile activity of the PAR2AP analogue tcLI-NH2, that was as active
      as SL-NH2 in the relaxation assay all argue in favour of receptor heterogeneity
      in the vasculature for the PAR2APs. It remains to be determined if the distinct
      endothelial receptor responsible for the contractile action of SL-NH2 can be
      proteolytically activated, like PAR1 and PAR2.

PMID- 9579741
TI  - Acetylcholine modulation of high-voltage-activated calcium channels in the
      neurones acutely dissociated from rat paratracheal ganglia.
AB  - 1. The modulation of high-voltage-activated (HVA) Ca2+ channels by acetylcholine
      (ACh) was studied in the paratracheal ganglion cells acutely dissociated from 2
      week-old Wistar rats by use of the nystatin perforated patch recording
      configuration under voltage-clamp conditions. 2. ACh inhibited the HVA Ca2+
      currents in a concentration- and voltage-dependent manner. 3. The inhibition was
      mimicked by a muscarinic agonist, oxotremorine. Pirenzepine and methoctramine
      produced parallel shifts to the right in the ACh concentration-response curves.
      Schild analysis of the ACh concentration-ratios yield pA2 values for pirenzepine
      and methoctramine of 6.85 and 8.57, respectively, suggesting the involvement of
      an M2 receptor. 4. Nifedipine, omega-conotoxin-GVIA and omega-conotoxin-MVIIC
      reduced the HVA I(Ca) by 16.8, 59.2 and 6.3%, respectively. A current insensitive
      to all of these Ca2+ antagonists, namely 'R-type', was also observed. The results
      indicated the existence of L-, N-, P/Q-, and R-type Ca2+ channels. 5. The ACh
      sensitive current component was markedly reduced in the presence of omega
      conotoxin-GVIA, but not with both nifedipine and omega-conotoxin-MVIIC. ACh also
      inhibited the R-type HVA I(Ca) remaining in saturating concentrations of
      nifedipine, omega-conotoxin-GVIA and omega-conotoxin-MVIIC. 6. The inhibitory
      effect of ACh was prevented by pretreatment with pertussis toxin. 7. It was
      concluded that ACh selectively reduces both the N- and R-type Ca2+ channels, by
      activating pertussis toxin sensitive G-protein through the M2 muscarinic receptor
      in paratracheal ganglion cells.

PMID- 9579742
TI  - Role of nitric oxide in the development and partial reversal of allergen-induced
      airway hyperreactivity in conscious, unrestrained guinea-pigs.
AB  - 1. Using a conscious, unrestrained guinea-pig model of allergic asthma, we
      investigated the role of endogenous nitric oxide (NO) in the regulation of airway
      (hyper)reactivity to histamine before and after the allergen-induced early and
      late asthmatic reactions, by examining the effect of inhalation of the NO
      synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 12 mM, 15 min)
      on the histamine-induced airway obstruction of ovalbumin-sensitized guinea-pigs
      before, and at 5.5 h and 23.5 h after allergen challenge. 2. Before allergen
      challenge, inhaled L-NAME caused a significant 2.02+/-0.25 fold increase (P<0.01)
      in airway reactivity to histamine; this effect was reversed within 2.5 to 6 h
      after administration. 3. After the allergen-induced early asthmatic reaction at 5
      h after ovalbumin provocation, a significant 3.73+/-0.67 fold increase (P<0.01)
      of the airway reactivity to histamine was observed; subsequent inhalation of L
      NAME at 5.5 h had no effect on the airway hyperreactivity, reassessed at 6 h. 4.
      After the late asthmatic reaction, at 23 h after ovalbumin provocation, a
      reduced, but still significant airway hyperreactivity to histamine (2.18+/-0.40
      fold; P<0.05) was observed. Subsequent inhalation of L-NAME now significantly
      potentiated the partially reduced airway hyperreactivity 1.57+/-0.19 fold
      (P<0.05) to the level observed after the early asthmatic reaction. 5. When
      administered 30 min before allergen exposure, L-NAME significantly enhanced the
      allergen-induced early asthmatic reaction. However, when administered at 5.5 h
      after allergen provocation, L-NAME did not affect the subsequent late asthmatic
      reaction. 6. These results indicate that endogenous NO is involved the regulation
      of histamine- and allergen-induced bronchoconstriction and that a deficiency of
      cNOS-derived NO contributes to the allergen-induced airway hyperreactivity to
      histamine after the early asthmatic reaction, while a recovery of NO deficiency
      may account for the partial reversal of the allergen-induced airway
      hyperreactivity after the late asthmatic reaction.

PMID- 9579743
TI  - Effect of some cyclooxygenase inhibitors on the increase in guanosine 3':5'
      cyclic monophosphate induced by NO-donors in human whole platelets.
AB  - 1. The effect of the NSAIDs indomethacin, indoprofen, diclofenac and
      acetylsalicylic acid on the increase in guanosine 3':5'-cyclic monophosphate
      (cyclic GMP) induced by nitric oxide-donor agents was tested in human whole
      platelets and in platelet crude homogenate. 2. In whole platelets, indomethacin
      reduced the increase in cyclic GMP induced by the nitric oxide-donors (NO-donors)
      sodium nitroprusside (NaNP) and S-nitroso-N-acetylpenicillamine (SNAP) in a dose
      dependent way, its IC50 being 13.7 microM and 15.8 microM, respectively. 3. Of
      the other cyclooxygenase inhibitors tested, only indoprofen reduced the increase
      in cyclic GMP induced by both NO-donors in a dose-dependent way (IC50=32.7
      microM, NaNP and 25.0 microM, SNAP), while acetylsalicylic acid (up to 1000
      microM) and diclofenac (up to 100 microM) were ineffective. 4. However, in
      platelet crude homogenate neither indomethacin nor indoprofen reduced the cyclic
      GMP production. 5. Indomethacin (10 microM), indoprofen (30 microM), diclofenac
      (100 microM) and acetylsalicylic acid (1000 microM) showed a comparable efficacy
      in inhibiting platelet thromboxane B2 (TXB2) production, suggesting that the
      inhibitory effect of indomethacin and indoprofen on the increase in cyclic GMP
      induced by both NO-donors was not mediated by inhibition of cyclooxygenase. 6. In
      vitro, the NSAIDs analysed did not interfere with nitrite production of SNAP. 7.
      The unhomogeneous behaviour of NSAIDs on the increase in cyclic GMP induced by NO
      donors in whole platelets may contribute to the different pharmacological and
      toxicological characteristics of the drugs, providing new knowledge on the effect
      of indomethacin and indoprofen.

PMID- 9579744
TI  - Characterization of calcitonin gene-related peptide (CGRP) receptors in
      intramural coronary arteries from male and female Sprague Dawley rats.
AB  - 1. In this study we characterized the CGRP-receptor subtype by Schild-plot
      analysis using the C-terminal fragment, human-alphaCGRP(8-37), a putative
      competitive CGRP1-receptor selective antagonist. In addition, the effect of rat
      alphaCGRP was compared with that of homologous peptides rat-betaCGRP, rat-amylin,
      rat-adrenomedullin and [Cys(Acm)2,7]-human-alphaCGRP, a putative selective CGRP2
      receptor agonist, in the left coronary arteries of 3 months old male and female
      Sprague Dawley rats. 2. Isolated rings from the distal, intramural part of the
      left anterior descending (LAD) coronary artery in both groups of rats were
      mounted on a double wire-myograph. The arteries were then stretched to their
      optimal lumen diameter for active tension development and precontracted with 10(
      5) M prostaglandin F2alpha (PGF2alpha), after which agonists were added to the
      organ bath in a cumulative manner. 3. Rat-alphaCGRP induced endothelium
      independent relaxations in male and female Sprague-Dawley rats. Rat-betaCGRP
      concentration-response relations (10[-11]-10[-7] M) were similar to those of rat
      alphaCGRP in either sex. The maximal relaxations induced by rat-amylin and rat
      adrenomedullin, both at 10(-6) M, were significantly (P<0.05) lower than those
      induced by rat-alpha- and rat-betaCGRP. In contrast, the selective CGRP2-receptor
      agonist [Cys(Acm)2,7]-human-alphaCGRP failed to induce significant relaxations at
      the highest concentration used (10[-7] M) in the coronary arteries of male and
      female rats. 4. The C-terminal fragment, human-alphaCGRP(8-37) blocked
      concentration-dependently (10[-7]-10[-6] M) the rat-alphaCGRP-induced relaxation
      in 10(-5) M PGF2alpha-precontracted coronary arteries. The slopes of the
      regression lines of the Schild-plots for both male and female rats were not
      significantly (P>0.05) different from unity and the pA2 values for human
      alphaCGRP(8-37) were 6.93 and 6.98 in arteries from male and female rats,
      respectively. There was no significant (P>0.05) difference in estimated pKB
      values for human-alphaCGRP(8-37) between male (6.99+/-0.10, n=13) and female
      (6.95+/-0.08, n=13) rats. 5. The concentration-response relationships for rat
      alpha- and rat-betaCGRP were similar in male and female Sprague Dawley rats. The
      predominant CGRP receptor subtype in small intramural coronary arteries appeared
      to belong to the CGRP1-receptor subtype in both sexes.

PMID- 9579745
TI  - Effect of the GABA uptake inhibitor tiagabine on sleep and EEG power spectra in
      the rat.
AB  - 1. The sleep profiles induced by agonists and agonistic modulators of gamma
      aminobutyric acidA (GABA[A]) receptors differ markedly. With regard to GABA(A)
      agonists, the effects may be due to the fact that these agents are poor
      substrates for uptake and are therefore likely to activate GABA(A) receptors
      tonically. To investigate this possibility, we assessed the sleep effects of two
      doses (2 and 10 mg kg[-1]) of the GABA re-uptake inhibitor tiagabine,
      administered intraperitoneally at light onset in 8 rats. Electroencephalogram
      (EEG) and electromyogram were recorded during the first 8 h after the injection.
      2. Compared with vehicle, tiagabine had minimal effects on the temporal pattern
      of non-rapid eye movement sleep (non-REMS) and on the total time spent therein.
      However, tiagabine dose-dependently elevated EEG activity during non-REMs, most
      prominently in the lower frequencies (1-8 Hz) and least pronounced in the
      frequencies between 11 and 16 Hz. During the first 2 h after the injection, 10 mg
      kg(-1) tiagabine elicited repetitive episodes of hypersynchronous EEG waves
      during wakefulness and slightly suppressed REMS. Except for these effects,
      tiagabine hardly influenced the time spent in and EEG activity during wakefulness
      and REMS. 3. The effects of tiagabine on state-specific EEG activity were
      qualitatively very similar to those elicited by GABA(A) agonists. These findings
      support the hypothesis that the influence of GABA(A) agonists on EEG signals may
      be caused by tonic stimulation of GABA(A) receptors.

PMID- 9579746
TI  - A modified framework for rural general practice: the importance of recruitment
      and retention.
AB  - Whilst definitions of what constitutes general practice vary according to
      purpose, the pivotal role of general practitioners as key providers of health and
      medical services is acknowledged. Recent concerns to address both what general
      practitioners and their patients want and get from general practice stem from a
      recognized need to include stakeholder concerns about the adequacy of general
      practice alongside workforce issues such as recruitment and retention. Nowhere is
      this need so crucial as in rural areas where the range of health services is
      limited and major inequities exist in the availability of general practitioners.
      An extended framework for evaluating what general practitioners and their
      patients expect and receive from general practice, with particular reference to
      rural general practice in Australia is presented. Three inter-related dimensions
      of recruitment, retention and a whole patient/whole family approach to health
      care are suggested as underpinning this framework. The significance of each
      dimension to ensuring the provision of quality general practice care in rural
      communities, and the links between them, are outlined in the proposed framework.

PMID- 9579747
TI  - Representing doctors: discourses and images in the Australian press.
AB  - Reports of incidents and issues related to members of the medical profession and
      the practice of medicine often feature in the western news media. Such intense
      coverage has incited the interest of both medical sociologists and members of the
      profession themselves. Thus far, however, very few detailed studies addressing
      the tenor of news reporting on the medical profession have been published,
      particularly in relation to the Australian media. This article presents the
      findings of a systematic and comprehensive analysis of the representation of
      doctors and the medical practice over a period of 15 months (January 1994 to
      March 1995) in metropolitan Australian newspapers and major news magazines. The
      method of critical discourse analysis was employed, including both quantitative
      analysis and interpretive analysis of the language and visual imagery of the news
      texts. The study revealed that negative portrayals of doctors were countered by
      positive representations. While cases of medical negligence, sexual assault and
      avarice on the part of doctors were often reported, medical successes were also
      frequently covered. Doctors were overwhelmingly reported as the major authorities
      on medical matters and as active agents in interacting with patients and other
      groups such as government officials. It is concluded that while the nature of
      reporting would suggest that members of the medical profession may be constantly
      under the spotlight of media scrutiny, they enjoy a significant degree of
      cultural and social authority in the Australian press.

PMID- 9579748
TI  - Porque me toco a mi? Mexican American diabetes patients' causal stories and their
      relationship to treatment behaviors.
AB  - This paper reports findings from an ethnographic study of self-care behaviors and
      illness concepts among Mexican-American non-insulin dependent diabetes mellitus
      (NIDDM) patients. Open-ended interviews were conducted with 49 NIDDM patients
      from two public hospital outpatient clinics in South Texas. They are self
      identified Mexican-Americans who have had NIDDM for at least 1 yr, and have no
      major impairment due to NIDDM. Interviews focused on their concepts and
      experiences in managing their illness and their self-care behaviors. Clinical
      assessment of their glucose control was also extracted from their medical
      records. The texts of patient interviews were content analyzed through building
      and refining thematic matrixes focusing on their causal explanations and
      treatment behaviors. We found patients' causal explanations of their illness
      often are driven by an effort to connect the illness in a direct and specific way
      to their personal history and their past experience with treatments. While most
      cite biomedically accepted causes such as heredity and diet, they elaborate these
      concepts into personally relevant constructs by citing Provoking Factors, such as
      behaviors or events. Their causal models are thus both specific to their personal
      history and consistent with their experiences with treatment success or failure.
      Based on these findings, we raise a critique of the Locus of Control Model of
      treatment behavior prevalent in the diabetes education literature. Our analysis
      suggests that a sense that one's own behavior is important to the disease onset
      may reflect patients' evaluation of their experience with treatment outcomes,
      rather than determining their level of activity in treatment.

PMID- 9579749
TI  - The influence of households on drinking behaviour: a multilevel analysis.
AB  - This paper examines the influence of household membership and area of residence
      on individual drinking behaviour using a multilevel modelling approach. The
      effects are investigated using data from the Health Survey for England (HSE) in
      which multiple interviews were conducted in the same household. With the use of
      postal address, the data were organised into a hierarchical structure of
      individuals within households within enumeration districts. After controlling for
      characteristics of individuals thought to influence or correlate with drinking
      behaviour, unexplained variation in alcohol consumption was attributed to
      individual, household and area effects. Household influences on drinking
      behaviour far outweigh the influences of place of residence. Policies aimed at
      reducing alcohol consumption, particularly by heavy drinkers, may be best
      targeted at the household level.

PMID- 9579751
TI  - Health and health expenditures in adjusting and non-adjusting countries.
AB  - The focus of this study is on the impact of World Bank structural adjustment
      operations on health expenditures and outcomes. We compare trends and levels of
      real per capita public spending on health, private consumption (which is the
      resource base for private health expenditures), and groupings child mortality
      indicators in four groups of countries. These are: (i) countries that started to
      borrow for the adjustment process early--Early Adjustment Lending (EAL)
      countries, (ii) Other Adjustment Lending (OAL) countries, (iii) Non-Adjustment
      Lending countries whose economies grew during the period 1985-1990 (NAL+), and
      (iv) Non-Adjustment Lending countries whose economies did not grow (NAL-). The
      NAL- group provides a 'counterfactual' for comparison with the two groups of
      adjusting countries. The results show that the fear about possible declines in
      health care spending in adjusting countries is unwarranted for EAL countries,
      that is those countries that started the adjustment process early and took it
      seriously. Government spending on health care increased on average for this group
      of countries, as did private consumption levels. Government health care
      expenditures also continued to increase in OAL countries, but mixed GDP growth
      performance has left little room for increased private spending. However, those
      countries that showed negative growth in the late eighties and did not start an
      adjustment process, fared worse throughout: real per capita public health care
      spending declined during the late eighties and increased less than in the other
      countries during 1989-1993, while private consumption has declined steadily. The
      trends in child mortality indicators show tremendous and continuing progress
      during the past two or three decades with few discernible differences among the
      four country groupings.

PMID- 9579750
TI  - The "three delays" as a framework for examining maternal mortality in Haiti.
AB  - Haiti has one of the highest rates of maternal mortality in the Caribbean. The
      "Three Delays" model proposes that pregnancy-related mortality is overwhelmingly
      due to delays in: (1) deciding to seek appropriate medical help for an obstetric
      emergency; (2) reaching an appropriate obstetric facility; and (3) receiving
      adequate care when a facility is reached. This framework was used to analyze a
      sample of 12 maternal deaths that occurred in a longitudinal cohort of pregnant
      Haitian women. Because of political upheavals in Haiti during the survey, these
      deaths are an underestimate of all deaths that occurred in the cohort. Family and
      friend interviews were used to obtain details about the medical and social
      circumstances surrounding each death. A delayed decision to see medical care was
      noted in eight of the 12 cases, whereas delays in transportation only appeared to
      be significant in two. Inadequate care at a medical facility was a factor in
      seven cases. Multiple delays were relevant in the deaths of three women. Family
      and friend interviews suggest that a lack of confidence in available medical
      options was a crucial factor in delayed or never made decisions to seek care.
      Expanding the coverage of existing referral networks, improving community
      recognition of obstetric emergencies, and improving the ability of existing
      medical institutions to deliver quality obstetric care, are all necessary.
      However, services will continue to be under-utilized if they are perceived
      negatively by pregnant women and their families. The current data thus suggest
      that improvements to Haiti's maternity care system which focus on reducing the
      third delay--that is, improving the quality and scope of care available at
      existing medical facilities--will have the greatest impact in reducing needless
      maternal deaths.

PMID- 9579752
TI  - Which terminally ill cancer patients receive hospice in-patient care?
AB  - The objective of this study was to investigate which terminally ill cancer
      patients receive in-patient care in hospices and other specialist palliative care
      in-patient units. An interview survey was made of family or others who knew about
      the last year of life of a random sample of people who died in 1990. Twenty
      district health authorities from a range of inner city, outer urban and rural
      settings took part. Although self-selected, districts were nationally
      representative in terms of social characteristics and on many indicators of
      health service provision and usage. Interviews were obtained for 2074 cancer
      deaths out of a random sample of 2915, a 71% response rate. 342 had been admitted
      to a total of 31 different hospices. Using logistic regression analysis five
      factors were found to independently predict hospice in-patient care: having pain
      in the last year of life, having constipation, being dependent on others for help
      with activities of daily living for between one and six months before death,
      having breast cancer, and being under the age of 85 years. A third of patients
      with all five factors were admitted, compared with no patients with none of these
      factors. It was found that symptom severity, age, dependency level and site of
      cancer played a role in determining hospice admission but have limited predictive
      value. Admission seems to be governed more by chance than by need. Further
      research is needed to identify which patients benefit most from in-patient care
      in hospices and other specialist palliative care units as the present
      arrangements appear to be both inequitable and insupportable.

PMID- 9579753
TI  - Equity is out of fashion? An essay on autonomy and health policy in the
      individualized society.
AB  - It is widely recognized that there is a discrepancy between principle and
      practice with respect to the health equity aim of public policy. This discrepancy
      is analyzed from two theoretical perspectives: the individualization of society
      and the fact that individual beliefs and values are connected to one's position
      in the social structure. These mechanisms influence both the choice of health
      policy measures and the normative judgements of preventive efforts, both of which
      tend to be consonant with the views of dominant social groups. In particular, we
      focus on the treatment of the ethical principle of autonomy and how this is
      reflected in health policy aimed at influencing health-related behaviour. We
      examine the current trend towards targeting health information campaigns on
      certain socio-economic groups and argue that it entails an ethical dilemma. The
      dominant discourse of the welfare state is contemplated as a means to understand
      why there tend to be a lack of emphasis on measures that are targeted at socio
      economic inequalities. It is argued that there is no substantive basis in the
      individualized society for perceiving health equity as an independent moral
      principle and that the driving force behind the professed health equity goal may
      be in essence utilitarian.

PMID- 9579754
TI  - The demand for prehospital emergency services in an aging society.
AB  - This research examines the implications of an aging society on the demand for
      prehospital emergency medical services (EMS). Using a large comprehensive set of
      population-based EMS utilization data (N = 73874) and population data from the
      1990 Census for the City of Dallas, Texas, rates of utilization for eight age
      groups were computed for total EMS incidents, incidents requiring transport
      services, and a sub-category of transport services for individuals requiring
      services for life-threatening conditions. The pattern of utilization associated
      with age was found to be tri-modal with rates rising geometrically with age for
      individuals aged 65 and over. Compared to the age group 45 to 64 years of age,
      rates of utilization for those aged 85 years and older were 3.4 times higher (P <
      0.001) for total EMS incidents, 4.5 times higher (P < 0.001) for emergency
      transports and 5.2 times higher (P < 0.001) for incidents of a life-threatening
      nature. A broad categorization of all EMS incidents by reason for requiring
      services indicates that the observed age-associated increase in utilization is
      due primarily to medical conditions rather than incidents arising from trauma.
      Finally, gender and racial/ethnic differences in utilization are briefly
      considered.

PMID- 9579755
TI  - Psychological distress and well-being among traumatized Palestinian women during
      the intifada.
AB  - Little is known about the ways in which Palestinian women who were subjected to
      political violence during the intifada coped with stress. This study investigated
      the extent to which differences in the presence of trauma, political and
      normative stressors, family resources, family coping, and family hardiness could
      account for variation in women psychological distress and well-being. Results
      indicated that normative stressors were more predictive of psychological distress
      and well-being than was the presence of trauma or political stressors. However,
      political stressors and normative stressors had albeit different effects on the
      mental health status of both traumatized and non-traumatized women. While the
      social-psychological resources of women were found to be negatively related to
      psychological distress and well-being, the sociodemographic resources had
      different patterns of relations. Also, family hardiness was evidenced to have an
      influence on perceived psychological distress among traumatized and non
      traumatized women, whereas effective coping and supportive resources may directly
      affect functioning among traumatized women only. The clinical and policy
      implications of these conclusions were discussed.

PMID- 9579756
TI  - Competing discourses of vital registration and personhood: perspectives from
      rural South Africa.
AB  - Whilst birth and death data derived from civil registration systems are regarded
      as essential indicators of health status and important for population planning,
      in developing countries they are usually perceived by civil servants and
      researchers to be very incomplete. In South Africa in 1994 only 50% of deaths
      were registered and 18% of births in the first year of life. A rapid qualitative
      study was undertaken in a rural district of South Africa to ascertain why
      registration levels of births, still-births and infant deaths are so low. Fifty
      five semi-structured interviews were conducted with 22 local Xhosa women and 33
      "professional" key informants, ranging from local civil servants to hospital
      staff and grave diggers. The study found that local people had complex notions of
      personhood, before birth and in the years following. Personhood was viewed as a
      process rather than a stage which is achieved through live birth, as is implied
      in discourses of vital registration. The women interviewed knew about birth
      registration although most had registered some or none of their children; they
      did not know of death registration. There was little knowledge of why
      registration was necessary and perceptions of this among all informant groups
      mostly related to the need for a certificate to achieve something else, such as
      an identity document or welfare payment. Confusion about the procedures to be
      followed was found among both women and professionals, who advised them. In
      circumstances in which certificates were officially required, for school entry
      and burial, other documentation were reported to be accepted. This suggests that
      the dominance of vital registration as a means of establishing official identity
      was not recognized. Registration was regarded as a means of achieving something
      else rather than and end in itself, which discourses of statistical and juridical
      importance imply. In the light of this we suggest that the present system be
      replaced by one based on "passive" registration in health care settings if
      substantially greater levels of completeness are to be achieved.

PMID- 9579757
TI  - Education and self-care activities among persons with rheumatoid arthritis.
AB  - Associations between low formal education and increased morbidity and mortality
      have been well established among persons with rheumatoid arthritis (RA) and other
      conditions. This study attempted to identify a partial explanation for the
      association between low education and poor outcomes among persons with RA by
      examining self-care activities performed by persons with different levels of
      education. Persons with 13+ yr of education were significantly more likely to
      perform specific self-care activities (e.g., using a heated pool, tub, shower, OR
      = 2.59; using relaxation methods, OR = 3.00; using stress control methods, OR =
      2.41; avoiding certain foods, OR = 1.74). The association between education and
      performance of self-care activities was not linear. When significant differences
      were noted, 13 yr of education was usually the point at which performance was
      significantly different than among lower education groups; individuals with 12 yr
      of education often exhibited lower frequencies of particular behaviors than did
      individuals with 9-11 yr of education. The association between higher education
      and performance of more self-care activities may shed light on previously
      described associations between education and morbidity. However, low education
      should not be viewed as the cause of increased morbidity and mortality, but as a
      proxy for a constellation of factors responsible for poor health outcomes.

PMID- 9579758
TI  - Women's decision-making in prenatal screening.
AB  - With serum screening (MS-AFP and hCG testing for Down's syndrome) women have to
      make several decisions in a limited time: whether to participate in the screening
      in the first place; then, if increased risk for fetal abnormality is detected,
      whether to have a diagnostic test, and finally, what to do if fetal abnormality
      is detected. The aim of this study was to examine how women themselves in an
      unselected population describe their decision-making in the different phases of
      serum screening. Women receiving a positive result from serum screening in two
      Finnish towns from September 1993 to March 1994 and a group of individually
      matched controls were invited to semistructured interviews; 45 index and 46
      control women (79% of those invited) participated between their 29th and 37th
      weeks of gestation (mean 31 weeks). Although serum screening was most often
      presented as voluntary or as an option, half the women described participation as
      a routine or self-evident act; only one-fourth of the women described actively
      deciding about participation. After a positive screening result, women's
      reactions to diagnostic tests, and their intentions if disability would be
      detected, varied greatly. Most of the women actively decided about having
      diagnostic tests, but for 23% participation in diagnostic testing was called a
      self-evident act. Women's intentions regarding abortion varied from a firm
      decision to abort to a firm decision not to abort, and many remained ambivalent.
      Prenatal screening, which demands the making of several decisions in a limited
      time and is offered to all pregnant women as part of established maternity care,
      is not based on every participant's active decision-making and thus creates an
      ethical problem. This problem should receive special attention from those who
      develop, introduce and decide on new health care practices.

PMID- 9579759
TI  - Gender differences in marital support following a shared life event.
AB  - Previous work has established that women with good marriages are less at risk of
      depression of clinical severity following a crisis than women in poor quality
      relationships. Evidence for such protectiveness is less clear for men. The paper
      examines the relationship between marital quality, onset of depression, and
      gender following a severely threatening life event. The results show that good
      quality of marriage related to lower rates of depression for both men and women,
      although the overall rate for women was higher. For women with a good marital
      relationship, but for whom support from partner was not forthcoming at the time
      of the crisis (i.e. the person was "let down"), risk was increased, confirming a
      result from a study in Islington. The current study shows that the same set of
      findings holds for men. Gender differences did emerge when the subjective need
      for support within the marital relationship is taken into account, with women
      expressing greater need. However, such a desire for support was not necessarily
      translated into support-seeking behaviour as in a poor relationship turning to a
      partner was frequently inopportune. Women were also more likely to seek support
      outside the marriage; as in the earlier Islington research this was related to a
      lower risk of depression for those in a poor relationship. An unexpected finding
      was that men who received support outside marriage had an increased risk of
      depression.

PMID- 9579760
TI  - Reductions in hospital use from self management training for chronic asthmatics.
AB  - The purpose of this study was to assess the impact of asthma Self Management
      Training on the health status and resource use of patients with chronic asthma.
      The study consisted of a randomized control design of chronic asthmatic patients
      in a tertiary care center in India. The intervention group (153 patients)
      received four training sessions in addition to the regular care provided to the
      control group (150 patients). Health status and resource use were measured at
      baseline and over a one year follow-up period. The intervention group had
      significantly better health status (measured by breathing ability), fewer
      productive days lost, and lower resource use (hospitalizations and emergency room
      visits) than the control group. Total annual costs (direct and indirect) were
      also lower, though physician costs were not included in the assessment.
      Therefore, incorporation of asthma Self Management Training as part of clinical
      management of asthma can result in improvements in health status and reductions
      in hospital use.

PMID- 9579761
TI  - Seeing is believing: more attention should be paid to right ventricular function.

PMID- 9579762
TI  - Symptomless hyperuricaemia in patients with essential hypertension and normal
      renal function.
AB  - In patients with essential hypertension who have apparently normal renal function
      it is not unusual for the serum uric acid to be elevated. This short review
      considers the implications of discovering hyperuricaemia in patients with
      essential hypertension.

PMID- 9579763
TI  - Right ventricular function in systemic hypertension.
AB  - The aim of the study was the assessment of right ventricular (RV) structure and
      diastolic function in hypertensive subjects. The study group consisted of 44
      patients with untreated, mild to moderate essential systemic hypertension. All
      the patients were in sinus rhythm, no symptoms of congestive heart failure,
      ischaemic or valvular heart disease and lung disorders were found. Twenty-six
      healthy subjects were the control group. M-mode echocardiographic measurements of
      the right ventricular wall (RVW) diastolic thickness, right ventricular outflow
      tract diameter (RVOTD), left ventricular (LV) structure and LV systolic function
      were performed. Pulsed Doppler echocardiography was used to measure peak early
      (TE) and peak atrial (TA) right ventricular diastolic filling velocities as well
      as velocity-time integrals (VTI-TE and VTI-TA). TE:TA and VTI-TE:VTI-TA ratios
      were calculated. Similar parameters of the left ventricular diastolic filling
      were recorded at the level of mitral annulus. Mean pulmonary artery pressure
      (MPAP) was measured non-invasively by the estimation of pulmonary artery systolic
      flows. We demonstrated in hypertensive patients significantly thicker RVW (3.94
      vs 2.8 mm, P < 0.001) and increased LV mass. In the hypertensive, increased TA
      and VTI-TA and diminished TE:TA and VTI-TE:VTI-TA ratios were recorded,
      indicating the abnormalities of RV diastolic function. RV diastolic filling
      parameters correlated positively with corresponding parameters of LV filling. The
      results of our study demonstrate that impairment of LV diastolic function, the
      common finding in systemic hypertension, is associated with diastolic
      disturbances of the right ventricle. RVW thickening and hypertrophy of
      interventricular septum seem to be major factors influencing RV diastolic
      function.

PMID- 9579764
TI  - Influence of the arm position on intra-arterial blood pressure measurement.
AB  - The reference level for the measurement of blood pressure (BP) is the level of
      the right atrium. In practice this is regularly disregarded, as the patient's arm
      is usually placed lower than the right atrial level. The aim of the study was to
      determine the influence of first, different arm positions and second, different
      transducer positions on the intra-arterially (i.a.) recorded BP. In 16 healthy
      men (age 28.1 +/- 8.0 (s.d.) years), i.a. BP was recorded at the left arm in
      supine position, using a 5-7 cm long cannula. The baseline position was with the
      tip of the cannula placed precisely at the level of the right atrium.
      Subsequently, the following changes were made: 5, 10, 15 and 20 cm above and 5,
      10, 15, and 20 cm below the baseline position. A 2-min rest period was allowed in
      each position before the BP was measured. The whole procedure was done either
      with the transducer connected to the arm at the place of the cannula (n = 7), or
      with the transducer placed next to the subject and continuously kept at the right
      atrial level during the BP measurement (n = 9). Simultaneously, baseline BP was
      measured indirectly, with a standard mercury sphygmomanometer, in the opposite
      arm maintained with the cubital fossa at the right atrial level during the whole
      procedure. This resulted in the first group of seven volunteers for both the i.a.
      systolic (SBP) and diastolic BP (DBP) values to significantly decrease (P <
      0.001) when the arm together with the transducer were elevated above the level of
      the right atrium, and returned to the initial value when the arm and the
      transducer were placed back at the right atrial level. Intra-arterial SBP and DBP
      significantly (P < 0.001) increased as the arm, together with the transducer,
      were lowered below the right atrial level and returned to the initial value when
      the arm and the transducer were placed back at the right atrial level. In both
      directions, each 5 cm change in the arm level was accompanied by a 3-4 mm Hg
      change in the i.a. BP value. The baseline BP, measured sphygmomanometrically at
      the contralateral arm, remained constant during the whole duration of the
      procedure. The changes in the i.a. BP were minimal in the second group of nine
      subjects in which only the arm but not the transducer was placed at different
      levels. We conclude that small deviations in arm position above or below the
      'gold standard', ie, the fossa cubiti at the right atrial level, will result in
      largely erroneous BP values. The correct positioning of the arm during BP
      measurement is therefore mandatory for the diagnosis and follow-up of
      hypertensive subjects.

PMID- 9579765
TI  - Ambulatory blood pressure monitoring and postprandial hypotension in elderly
      patients with isolated systolic hypertension. Systolic Hypertension in Europe
      (SYST-EUR) Trial Investigators.
AB  - The present analysis was undertaken to evaluate postprandial (PP) changes in
      blood pressure (BP) assessed with ambulatory BP monitoring (ABPM) in elderly
      subjects with isolated systolic hypertension (ISH) on conventional measurement. A
      total of 530 patients (335 women and 195 men, aged 60-100 years, median 70 years)
      who performed an ABPM during the placebo run-in period of the Syst-Eur trial were
      included into the analysis. The PP changes in BP and heart rate (HR) were
      calculated by subtracting the mean systolic BP (SBP), diastolic BP (DBP) and HR
      in the 2 h preceding the main meal from the corresponding means covering the 2 h
      after the meal. The reproducibility of the postprandial fall in BP and heart rate
      (PPH) was assessed by contrasting the first and second ABPM in a subgroup of 147
      patients who performed two ABPM's during the placebo run-in period. The mean SBP
      and DBP decreased and reached the nadir 2 h after the main meal while HR did not
      change. When PPH was assessed by comparing BP in the 2 h before and after the
      meal, both SBP and DBP decreased significantly (respectively -6.6 mm Hg, -5.4 mm
      Hg; P < 0.001). In 67.6% of all patients a decrease in SBP was observed and in
      24.1% it exceeded 16 mm Hg. The corresponding values for DBP were 71.3% and 24.5%
      (DBP decreased more than 12 mm Hg). A greater fall in DBP was associated with a
      greater decrease in HR (r = 0.20, P < 0.001), while changes in SBP and HR were
      not interrelated. Regression analysis did not identify any significant covariate
      of PPH. Group means of PPH could be reproduced without significant changes in
      their values, but the within-subject reproducibility of the PP changes was low.
      There were no differences in PPH according to the place of residence of the
      patients. In conclusion, the descriptive analysis of the meal-induced changes in
      ABPM in elderly subjects with ISH showed that in every day circumstances most of
      them experience falls in both SBP and DBP within 2 h after the meal.

PMID- 9579766
TI  - Variability in vascular responsiveness between Mexican-Americans and White
      Americans.
AB  - Ethnic differences in vascular adrenergic responsiveness have been implicated to
      be a potentially important mechanism which may be responsible for some of the
      variations in haemodynamic patterns between races. These differences may account
      for the variability in the prevalence of hypertension in different groups. The
      main aim of this study was to determine whether there was a difference in venous
      responsiveness to the vasoactive agents, phenylephrine and isoproterenol, between
      Mexican-Americans and White Americans. Isoproterenol is a potent non-selective
      beta-adrenergic agonist, phenylephrine is an alpha1-selective adrenergic agonist.
      Using the dorsal hand vein compliance technique, dose-response curves were
      constructed for the two vasoactive agents in 10 Mexican-American and 10 White
      American volunteers. The maximal venoconstriction for phenylephrine in the
      Mexican-American group was significantly less than that of the Whites in the
      study (71.2 +/- 20.1% vs 89.4 +/- 10.9%, P < 0.05). The log ED50 for
      isoproterenol in the Mexican-American group was also significantly greater than
      that for Whites (1.68 +/- 0.35[47.6 ng/min] vs 1.19 +/- 0.55[15.5 ng/min], P <
      0.05). These results suggest that Mexican-Americans have a differential
      responsiveness to adrenergic vasoactive agents compared to White Americans and
      may be protected from the development of hypertension.

PMID- 9579767
TI  - Alteration of carotid circulation in essential hypertensive patients with left
      ventricular hypertrophy.
AB  - To investigate carotid haemodynamic characteristics in essential hypertensive
      patients with left ventricular hypertrophy, we evaluated the structure and
      function as well as blood flow of the common carotid artery by using a
      combination of B-mode ultrasound and pulsed-Doppler in control subjects (n = 38),
      and hypertensive patients with (n = 40) and without (n = 27) left ventricular
      hypertrophy. Hypertensive patients had a higher intima-medial thickness compared
      with control subjects. Diastolic/systolic flow velocity ratio as well as flow
      volume ratio was significantly decreased in hypertensive patients with left
      ventricular hypertrophy in association with decline of distensibility of the
      common carotid artery. In the hypertensive patients with left ventricular
      hypertrophy, diastolic/systolic flow velocity ratio as well as flow volume ratio
      had significant correlation with diastolic blood pressure, pulse pressure and
      carotid arterial distensibility. These findings indicate that diastolic blood
      flow in the common carotid artery is impaired in hypertensive patients with left
      ventricular hypertrophy. Decreased distensibility and low diastolic perfusion
      pressure may be the underlying mechanisms.

PMID- 9579768
TI  - Assessment of the acute arterial effects of converting enzyme inhibition in
      essential hypertension: a double-blind, comparative and crossover study.
AB  - In subjects with essential hypertension, angiotensin-converting enzyme (ACE)
      inhibition increases arterial diameter, compliance and distensibility of
      peripheral muscular arteries in association with blood pressure reduction.
      Whether pulse pressure amplification is modified by ACE inhibition and whether
      changes in compliance and distensibility are due to a drug effect on the arterial
      wall, to the blood pressure reduction or to a combination of both factors, is
      largely ignored. In a randomised, double-blind crossover trial, we used the ACE
      inhibitor quinapril as a marker to evaluate the changes in: pulse pressure
      amplification (applanation tonometry), carotid compliance and distensibility
      (echo-tracking technique), and aortic distensibility (measured from pulse wave
      velocity). Quinapril decreased in the same extent carotid and brachial pulse
      pressure, thus causing a resetting of pulse pressure amplification toward normal
      values. Carotid compliance and distensibility as well as aortic distensibility
      increased significantly. Based on three-way analysis of variance, it was shown
      that, whereas the changes in carotid stiffness were exclusively due to blood
      pressure reduction and not to a drug-induced relaxation of the arterial wall, the
      changes in aortic distensibility were due to the combination of both factors.
      Thus, using an atraumatic non-invasive procedure, it was possible to show that:
      (i) ACE inhibition is able to maintain pulse pressure amplification, an important
      factor contributing to reduce the afterload of the heart; and (ii) ACE inhibition
      alters the hypertensive arterial wall in a very heterogeneous manner, with a
      maximal drug effect on muscular large arteries like the abdominal aorta, and not
      on elastic arteries like the carotid artery and the thoracic aorta.

PMID- 9579769
TI  - Renin status does not predict the anti-hypertensive response to angiotensin
      converting enzyme inhibition in African-Americans. Trandolapril Multicenter Study
      Group.
AB  - The angiotensin-converting enzyme (ACE) inhibitor trandolapril, a non-sulfhydryl
      prodrug which is hydrolysed into trandolaprilat, was studied in 322 hypertensives
      of African-American descent using a double-blind, randomised, placebo-controlled,
      parallel study design. Following 6 weeks of double-blind treatment with placebo
      or 0.25 to 16 mg/day trandolapril, an analysis of drug effect on trough blood
      pressure (BP) stratified by age, gender, weight, pre-treatment plasma renin
      activity, and trandolaprilat concentration was performed. Two mg was the lowest
      effective trandolapril dose, whereas doses above 4 mg did not significantly
      reduce trough BP. Reduction in BP did not correlate with trough plasma
      trandolaprilat concentration. Pre-treatment plasma renin activity was not a
      reliable indicator of anti-hypertensive response, as similar reductions in BP
      occurred even in patients with the lowest renin levels. There were no observable
      differences based on age, gender or measurements of the renin-angiotensin
      aldosterone axis. In conclusion, neither age, gender or plasma renin activity
      influenced anti-hypertensive response to angiotensin-converting enzyme inhibition
      in African-Americans.

PMID- 9579770
TI  - Opposite associations of circulating aldosterone and atrial natriuretic peptide
      with left ventricular diastolic function in essential hypertension.
AB  - It has been shown in animal experiments that angiotensin II and aldosterone have
      mitogenic effects on the cardiovascular system, whereas atrial natriuretic
      peptide has antimitogenic properties. The aim of the present study was to relate
      plasma renin activity, angiotensin II, aldosterone and atrial natriuretic peptide
      to left ventricular structure and function, assessed by use of imaging
      echocardiography and transmitral Doppler velocimetry in 73 patients with
      essential hypertension, World Health Organization stages I-II, aged 43 +/- 10
      (s.d.) years. Left ventricular mass, wall thickness and internal diameter were
      not independently related to the biochemical variables, except for a weak and
      positive association of wall thickness with plasma aldosterone (P = 0.06).
      However, left ventricular early inflow peak velocity and deceleration were
      independently and inversely related to age (P < 0.001) and to plasma aldosterone
      (P < 0.01), and positively to plasma atrial natriuretic peptide (P < 0.05). Peak
      flow velocity during atrial contraction was positively related to plasma atrial
      natriuretic peptide both before (P < 0.001) and after (P < 0.05) controlling for
      significant covariates (age, sex and blood pressure). We conclude that
      circulating renin, angiotensin II, aldosterone and atrial natriuretic peptide are
      not independently related to left ventricular mass in essential hypertension. The
      inverse association of plasma aldosterone with indices of diastolic function is
      compatible with a stimulating effect of aldosterone on myocardial fibrosis, which
      is opposed by atrial natriuretic peptide. The apparently conflicting positive
      association of this peptide with atrial peak velocity is most likely due to
      stimulation of its secretion by atrial involvement.

PMID- 9579772
TI  - Sensory information processing in the dorsal column nuclei by neuronal
      oscillators.
AB  - The dorsal column nuclei, a first relay station of the somatosensory system,
      express coherent oscillatory activity in the 4-22 Hz frequency range at single
      unit, multiunit and local field potential levels. This activity appears
      spontaneously (33% of the cases) or, more commonly (83%), during natural sensory
      stimulation of the receptive field. Such oscillations are not imposed upon the
      dorsal column nuclei by incoming sensory afferents nor cortico-nuclear
      projections, which indicates that they are generated within the dorsal column
      nuclei. We concluded that dorsal column nuclei transform a non-rhythmic input
      from the periphery to a populational oscillatory output to the somatosensory
      thalamus during sensory stimulation.

PMID- 9579771
TI  - A randomised, double-blind comparison of the angiotensin II receptor antagonist,
      irbesartan, with the full dose range of enalapril for the treatment of mild-to
      moderate hypertension.
AB  - OBJECTIVE: To compare the anti-hypertensive efficacy, safety, and tolerability of
      irbesartan with those of the full dose range of enalapril in patients with mild
      to-moderate hypertension. DESIGN AND METHODS: A total of 200 patients were
      randomised to irbesartan 75 mg or enalapril 10 mg (once daily). Doses were
      doubled at Weeks 4 and/or 8 if seated diastolic blood pressure (DBP) was > or =
      90 mm Hg. Trough blood pressure was measured after completion of a 4- to 5-week
      placebo lead-in period and again after 2, 4, 8, and 12 weeks of treatment. MAIN
      OUTCOME MEASURES: Efficacy was evaluated by determining the change from baseline
      in trough seated blood pressure and the proportion of patients normalised (seated
      DBP <90 mm Hg) at Week 12. Safety and tolerability were assessed by adverse
      events reported by physicians, by patients in response to a specific-symptoms
      questionnaire, by open-ended questioning of patients by physicians, and by
      clinical laboratory evaluations. RESULTS: Both treatments significantly lowered
      blood pressure with no significant difference in efficacy between treatment
      groups. At Week 12, the percentage of patients titrated to either enalapril 40 mg
      or irbesartan 300 mg was 24% and 28%, respectively. The frequency of overall
      adverse events was similar in both groups. The incidence of cough in the
      enalapril and irbesartan groups was 17% and 10%, respectively. In contrast to
      other AII receptor antagonists, there was no change in uric acid concentrations
      with irbesartan. CONCLUSIONS: Irbesartan was as effective as the full dose range
      of enalapril. Irbesartan also demonstrated an excellent tolerability profile.

PMID- 9579773
TI  - Quantal processing of visual information in the brain.
AB  - In order to test if vision is a continuous processing system that analyses
      information immediately after it arrives at the retina or a discontinuous system
      that accumulates information and periodically analyses a data quantum, the time
      required by 38 healthy adults to solve simple visual tasks was accurately
      quantified. The main finding of the present study was that the processing time
      for visual tasks is always a multiple of a basic unit whose duration was 30-40
      ms. Present data support the hypothesis that visual information is processed in
      the brain with a discontinuous flow of discrete-time quanta. Data suggest two
      processing ways for the visual system, one that with a high time-resolution (30
      40 ms) operates under high-illumination conditions, and the other that with a low
      time-resolution (100-120 ms) is put into operation in low-illumination
      conditions.

PMID- 9579774
TI  - Optical responses evoked by cerebellar surface stimulation in vivo using neutral
      red.
AB  - The pH sensitive dye, Neutral Red, was used with optical imaging techniques to
      map intracellular pH shifts elicited by cortical surface stimulation of the rat
      cerebellum. In the in vivo rat cerebellar cortex stained with Neutral Red, a
      brief stimulus train (three stimuli at 33 Hz) evoked a longitudinal beam of
      increased fluorescence (acidic shift) running parallel to the long axis of the
      folium within 100 ms of stimulation onset. A 5-10 s stimulus train (5-20 Hz)
      produced a biphasic optical response consisting of a beam of increased
      fluorescence (acidic shift) which returned to baseline in approximately 60 s,
      followed by a beam of decreased fluorescence (alkaline shift) for up to 120 s. A
      close spatial correspondence was observed between electrophysiological and
      optical maps of the response to surface stimulation. Application of acetazolamide
      enhanced the optical signals, acetabenzolamide-phenoxyethene had no effect, and
      the glutamate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, decreased the
      optical signals. Increased fluorescence was produced by superfusion of the
      cerebellar cortex with acidic Ringer solutions and a decrease in fluorescence by
      basic solutions. These fluorescence changes also occurred in the presence of
      several ion channel/receptor blockers. Increased fluorescence resulted from
      superfusion with Ringer solution containing sodium propionate and decreased
      fluorescence with the transition from 5% carbon dioxide to nominally carbon
      dioxide-free Ringer solution. Recovery from acid loading with ammonium chloride
      was prevented by amiloride, an inhibitor of the Na+/H+ transporter. Application
      of Ringer solution with high potassium concentration produced an increase in
      fluorescence but only a decrease in fluorescence was detected when neuronal
      blockers were present, an effect consistent with a glial contribution. This
      decrease in fluorescence was blocked by adding barium. No epifluorescent optical
      signals were obtained from unstained preparations or preparations stained with
      cell-permeant fluorescence markers, suggesting little contribution from activity
      dependent volume changes and other intrinsic signals. These results demonstrate
      that the Neutral Red optical signals evoked by cerebellar surface stimulation are
      primarily pH based and include a significant component related to intracellular
      pH shifts. The large amplitudes of these optical signals are particularly useful
      for mapping neuronal activity. Furthermore, this technique provides a novel tool
      for the study of pH changes in vivo at both high spatial and temporal resolution.

PMID- 9579775
TI  - Postsynaptic pyramidal target selection by descending layer III pyramidal axons:
      dual intracellular recordings and biocytin filling in slices of rat neocortex.
AB  - Paired intracellular recordings in slices of adult rat neocortex with biocytin
      filling of synaptically connected neurons were used to investigate the pyramidal
      targets, in layer V, of layer III pyramidal axons. The time-course and
      sensitivity of excitatory postsynaptic potentials to current injected at the
      soma, and locations of close appositions between presynaptic axons and
      postsynaptic dendrites, indicated that the majority of contributory synapses were
      located in layer V. Within a "column" of tissue, radius < or = 250 microm, the
      probability that a randomly selected layer III pyramid innervated a layer V
      pyramid was 1 in 4 if the target cell was a burst firing pyramid with an apical
      dendritic tuft in layers II/I. If, however, the potential target was a regular
      spiking pyramid, the probability of connectivity was only 1 in 40, and none of
      the 13 anatomically identified postsynaptic layer V targets had a slender apical
      dendrite terminating in layers IV/III. Morphological reconstructions indicated
      that layer III pyramids select target layer V cells whose apical dendrites pass
      within 50-100 microm of the soma of the presynaptic pyramid in layer III and
      which have overlapping apical dendritic tufts in the superficial layers. The
      probability that a layer V cell would innervate a layer III pyramid lying within
      250 microm of its apical dendrite was much lower (one in 58). Both presynaptic
      layer III pyramids and their large postsynaptic layer V targets could therefore
      access similar inputs in layers I/II, while small layer V pyramids could not. One
      prediction from the present data would be that neither descending layer V inputs
      to the striatum or thalamus, nor transcallosal connections would be readily
      activated by longer distance cortico-cortical "feedback" connections that
      terminated in layers I/II. These could, however, activate corticofugal pathways
      to the superior colliculus or pons, both directly and via layer III.

PMID- 9579776
TI  - Influences of area 17 on neuronal activity of simple and complex cells of area 18
      in cats.
AB  - To understand the influence of the ascending path linking area 17 to area 18 of
      visual cortices, experiments were carried out in which a small neuronal
      population of area 17 was inactivated with GABA, while unitary responses were
      recorded in area 18. In the latter, cells are identified as belonging to the
      simple or complex family according to their firing pattern evoked in response to
      sine-wave gratings scrolling through the receptive fields. Anesthetized cats were
      prepared for single-cell recordings. In area 17, a GABA-containing pipette was
      placed in superficial layers in order to inactivate reversibly a small neuronal
      population. Prior to blockade, the orientation tuning curves were obtained in
      both areas and the difference in optimal orientation between areas 17 and 18 was
      recorded. In area 18, cells were classified as simple or complex. The strategy
      was to study the reaction of neurons in area 18 prior to, during and after area
      17 depression. In most simple cells, whenever the difference in orientation was
      in the iso-range, that is when the difference in optimal orientations of the
      injected site (in area 17) and of the neuron in area 18 was less than 30 degrees,
      the GABA application produced a decline of the evoked discharges, whereas GABA
      injection augmented the evoked firing rate when the difference was in the cross
      range (>60 degrees). In contrast to simple cells, GABA depression enhanced the
      responses in the majority of complex cells with like orientations in both areas.
      When the difference between recording sites was in the cross-range, then area 17
      depression produced weaker evoked firing. A tangential penetration of the
      injecting pipette, allowing injection of different orientation sites while
      testing the same unit in area 18, revealed that the latter could react with an
      enhancement or a decline of the responses as the injecting pipette shifted from
      iso (or cross) to cross (or iso) disparity in optimal orientations between areas
      17 and 18. These results suggest that the path connecting area 17 to area 18 may
      be functionally discriminated on the basis of the orientation domain and cell
      types. In addition, our data suggest that the ascending visual streams are
      required to generate orientation specificity in area 18.

PMID- 9579777
TI  - Spatial frequency processing in posteromedial lateral suprasylvian cortex does
      not depend on the projections from the striate-recipient zone of the cat's
      lateral posterior-pulvinar complex.
AB  - It is generally considered that the posteromedial part of the cat's lateral
      suprasylvian cortex is involved in the analysis of image motion. The main
      afferents of the posteromedial lateral suprasylvian cortex come from a direct
      retinogeniculate pathway and indirect retinotectal and retino-geniculo-cortical
      pathways. Removal of the primary visual cortex does not affect the spatial and
      temporal processing of suprasylvian cortex cells suggesting that these properties
      are derived from thalamic input. We have investigated the possibility that the
      striate-recipient zone of the lateral posterior nucleus-pulvinar complex may be
      responsible for the spatial (and temporal) frequency processing in posteromedial
      lateral suprasylvian cortex since these two regions establish strong
      bidirectional connections and share many visual properties. Experiments were done
      on anaesthetized normal adult cats. Visual responses in suprasylvian cortex were
      recorded before, during, and after the deactivation of the lateral part of the
      lateral posterior nucleus accomplished by the injection of lidocaine or GABA.
      Results can be summarized as follows. A total of 64 cells was tested. Out of this
      number, 11 units were affected by the deactivation of the lateral part of lateral
      posterior nucleus and one cell, by the blockade of pulvinar. For all cells,
      except one, the effect consisted in a global reduction of the evoked discharge
      rate suggesting that the thalamo-suprasylvian cortex projections are excitatory
      in nature. We did not find any significant differences in the optimal spatial
      frequency, nor in the width of the tuning function, whether the grating was
      presented at half- or saturation contrast. In addition, there were no significant
      differences between the low- and high cut-off spatial frequency values computed
      before and after the deactivation of the lateral posterior nucleus. No specific
      changes were observed in the contrast sensitivity function of the posteromedial
      lateral suprasylvian cortex cells. Similar results were observed with respect to
      the temporal frequency tuning functions. Deactivating the lateral posterior
      nucleus did not modify the direction selectivity nor the organization of the
      subregions of the lateral suprasylvian cortex "classical" receptive fields. The
      absence of strong changes in posteromedial lateral suprasylvian cortex cell
      response properties following the functional blockade of the lateral posterior
      nucleus suggests that the projections from this part of the thalamus are not
      essential to generate the spatial characteristics of most posteromedial lateral
      suprasylvian cortex receptive fields. These properties may be derived from other
      thalamic inputs (e.g., medial interlaminar nucleus) and/or from the intrinsic
      computation of the afferent signals within the lateral suprasylvian cortex. On
      the other hand, it is possible that the lateral posterior nucleus lateral
      suprasylvian cortex loop may be involved in other functions such as the analysis
      of complex motion as suggested by the findings from our and other groups.

PMID- 9579778
TI  - Selective and invariant sensitivity to crosses and corners in cat striate
      neurons.
AB  - Many neurons (56/174, or 32.2%) studied in the cat striate cortex (area 17)
      increased significantly (by 3.3 times on average) their responses under
      stimulation by cruciform or corner figures of specific or non-specific shape and
      orientation flashing in receptive field as compared with single light bar of
      preferred orientation. Most of these neurons (71.4%) were found to be highly
      selective to both the shape (the angle between the figure's lines) and
      orientation of these figures. In the neuronal selection studied we have also
      found all possible types of invariance of the cross and corner tuning to
      orientation and/or shape of these figures. We found neurons with selectivity to
      the form of the figures and invariance to their orientation and, on the contrary,
      units invariant to shape but selective to orientation. Some cells were found
      invariant to both the form and orientation of the cruciform or corner figure but
      highly sensitive to appearance of any such figure in the receptive field. Two
      main hypotheses about the mechanisms of selective sensitivity to crosses and
      angles can be considered. They are as follows: an excitatory convergence of two
      units with different preferred orientations, and intracortical inhibitory
      interactions. The cells with double orientation tuning for a single bar are found
      relatively rarely (about 20%), thus making the first suggestion the most
      unlikely. This circumstance is of special importance since it provides evidence
      against the hierarchic formation of the higher-order cortical units from a set of
      lower-order cells that is still under discussion. The units with high sensitivity
      to cross or corner seem to be ideally suitable for their selection, rather than
      to serve as classical orientation detectors only.

PMID- 9579779
TI  - Generators of visual evoked potentials investigated by dipole tracing in the
      human occipital cortex.
AB  - Current source generators (dipoles) of the human visual evoked potentials to
      pattern-onset stimuli were investigated with the dipole tracing method, using a
      realistic four-layer head model of scalp-skull-fluid-brain, which can equate the
      surface potential distributions on a scalp to one or two corresponding equivalent
      dipoles. Three healthy adult human subjects were used, and 29 electrodes were set
      on a scalp of each subject. Visual stimulus of a checkerboard pattern was
      presented for 250 ms in each of eight different visual fields (central and
      peripheral parts of each of four quadrant fields). The visual evoked potentials
      consisting of initial positive-late negative waves (CI and CII components
      designated by Jeffreys and Axford) were recorded mainly on the occipital region
      contralateral to stimulated visual fields. The initial positive wave (CI) of
      visual evoked potentials were divided into two components: early component of the
      CI (e-CI--an early small positive deflection with approximate peak latency of 70
      90 ms) and late component of the CI (l-CI--a late large positive deflection with
      approximate peak latency of 100-120 ms). The dipole with a fit exceeding 98%
      dipolarity with our model at the shortest latencies was defined as an "earliest
      dipole" of the evoked potentials, produced by the primary responses in the
      occipital cortex to an afferent volley from the lateral geniculate body. These
      earliest dipoles, for eight different visual field stimulations, were estimated
      at the approximate peak of the e-CI. Estimated dipoles were superimposed on a
      three-dimensional magnetic resonance image of each subject's brain. Earliest
      dipoles for right upper and right lower quadrant-field stimulations were located
      at the left calcarine cortices below and above the calcarine fissure,
      respectively; earliest dipoles for left upper and left lower quadrant-field
      stimulations were located at the right calcarine cortices below and above the
      calcarine fissure, respectively. Furthermore, earliest dipoles for central and
      peripheral quadrant-field stimulations were located posteriorly and anteriorly in
      the calcarine cortex, respectively. The results from these non-invasive analyses
      of visual evoked potentials indicated topographic localization of the dipoles
      around the calcarine fissure based on the loci of the visual fields. This was
      comparable to the retinotopy of the human occipital lobe based on
      clinicopathological studies.

PMID- 9579780
TI  - Contralateral cortical projection to the mediodorsal thalamic nucleus: origin and
      synaptic organization in the rat.
AB  - The origin of the corticothalamic projections to the contralateral mediodorsal
      nucleus, the collateralization of cortical fibers and their synaptic organization
      in the ipsi- and contralateral mediodorsal nuclei were investigated in adult rats
      with double retrograde fluorescent and anterograde tracing. After tracer
      injections in the mediodorsal nuclei on either side, neurons were retrogradely
      labeled in all the areas of the contralateral prefrontal cortex in which
      ipsilateral labeling was also observed. Contralateral corticothalamic cells
      accounted for 15% of the labeled neurons in the orbital and agranular insular
      areas, while their proportion was lower (3%) in the anterior cingulate cortex. Up
      to 70% of the contralateral cortical neurons were double labeled by bilateral
      injections in the mediodorsal nuclei. At the electron microscopic level,
      unilateral injections of biotinylated dextran-amine in the orbitofrontal cortex
      resulted in anterograde labeling of small terminals and a few large boutons in
      the ipsilateral mediodorsal nucleus, while only small boutons were identified
      contralaterally. The diameter of postsynaptic dendritic profiles contacted by
      labeled small cortical endings was significantly larger in the ipsilateral
      mediodorsal nucleus than contralaterally. These findings demonstrate that dense
      contralateral cortical projections to the mediodorsal nucleus derive from the
      orbital and agranular insular areas, and that crossed corticothalamic afferents
      are mostly formed by collaterals of the ipsilateral connections. Our observations
      also point out the heterogeneity of corticothalamic boutons in the rat
      mediodorsal nucleus and morphological differences in the synaptic organization of
      prefrontal fibers innervating the two sides, indicating that ipsilateral cortical
      afferents may be more proximally distributed than crossed cortical fibers on
      dendrites of mediodorsal neurons.

PMID- 9579781
TI  - Infracortical interstitial cells concurrently expressing m2-muscarinic receptors,
      acetylcholinesterase and nicotinamide adenine dinucleotide phosphate-diaphorase
      in the human and monkey cerebral cortex.
AB  - Intense immunoreactivity for the m2-muscarinic receptor was found in a population
      of interstitial polymorphic neurons embedded within the infracortical white
      matter and the adjacent deep layers of the cerebral cortex. These infracortical
      neurons were evenly distributed throughout architectonic subdivisions of the
      monkey cortex except for parts of primary visual cortex where they were less
      numerous. A similar set of m2-immunoreactive interstitial cells was also detected
      in the human lateral temporal neocortex obtained at surgery. Upon electron
      microscopic examination, they were found to receive unlabelled synaptic inputs
      and displayed abundant rough endoplasmic reticulum, a prominent nucleolus, and
      invaginations of the nuclear membrane. Double labelling of m2 immunoreactivity
      and acetylcholinesterase histochemistry demonstrated that approximately 90% of
      the m2-positive infracortical cells were acetylcholinesterase-rich in the monkey
      and human brains. Conversely, the proportion of acetylcholinesterase-rich
      infracortical neurons that were m2-immunoreactive was over 90% in the monkey and
      at least 50% in the human. The concurrent visualization of nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d) enzyme activity with m2
      immunoreactivity in the monkey and human brain showed that 85-95% of m2
      immunoreactive infracortical cells were NADPH-d positive. Conversely, about 70%
      of NADPH-d cells contained m2 immunoreactivity. These observations provide the
      most convincing information to date that many of the acetylcholinesterase-rich
      neurons located in the infracortical white matter of the cerebral cortex are
      likely to be cholinoceptive. The expression of NADPH-d by these neurons suggests
      that they may also provide a relay through which cholinergic innervation,
      originating predominantly from the nucleus basalis of Meynert, could regulate the
      release of nitric oxide in the cerebral cortex and subjacent white matter. The
      degeneration of these neurons may account for at least some of the depletion of
      m2 receptors that has been reported in Alzheimer's disease.

PMID- 9579782
TI  - Hippocampal grafts of acetylcholine-producing cells are sufficient to improve
      behavioural performance following a unilateral fimbria-fornix lesion.
AB  - Lesions of the septohippocampal pathway produce cognitive deficits that are
      partially attenuated by grafts of cholinergic-rich tissue into denervated target
      regions or by systemic administration of cholinomimetic drugs. In the present
      study, fibroblasts engineered to produce acetylcholine were used to test the
      hypothesis that restoration of hippocampal acetylcholine in rats with
      septohippocampal lesions is sufficient to improve cognitive processing post
      damage. Rats received unilateral grafts of acetylcholine-producing or control
      fibroblasts into the hippocampus immediately prior to an aspirative lesion of the
      ipsilateral fimbria-fornix. Some rats with fimbria-fornix lesions were implanted
      with acetylcholine-producing or control fibroblasts into the neocortex, another
      major target of the basal forebrain cholinergic system, to determine if the site
      of acetylcholine delivery to the damaged brain is critical for functional
      recovery. Rats were tested in a hidden platform water maze task, a cued water
      maze task and activity chambers between one and three weeks post-grafting.
      Compared to unoperated controls, rats with fimbria fornix lesions only were
      significantly impaired in hidden platform water maze performance. Hippocampal
      grafts of acetylcholine-producing cells reduced lesion-induced deficits in the
      water maze, whereas hippocampal control grafts and cortical grafts of either cell
      type were without effect. Locomotor activity and cued water maze performance were
      unaffected by the lesion or the implants. Taken together, these data indicate
      that water maze deficits produced by fimbria fornix lesions, which disrupt a
      number of hippocampal neurotransmitter systems, can be attenuated by target
      specific replacement of acetylcholine in the hippocampus and that this recovery
      occurs in the absence of circuitry repair.

PMID- 9579783
TI  - In vivo electrophysiological investigations into the role of histamine in the
      dentate gyrus of the rat.
AB  - Drugs acting at the three known classes of histamine receptors were injected
      intracerebroventricularly into the rat. The effects of these drugs upon synaptic
      potentials recorded from the dentate gyrus of the freely-moving rat were
      determined. Population spikes and field excitatory postsynaptic potentials were
      recorded from the granule cell layer of the dentate gyrus following stimulation
      of the perforant path. Drugs, dissolved in 0.9% NaCl were applied into the
      lateral cerebral ventricle in a volume of 5 microl over a period of 6 min. The
      histamine H1 receptor antagonist mepyramine (0.4 or 0.8 microg) had no
      significant effect on population spikes or field excitatory postsynaptic
      potentials. In contrast the H2 receptor antagonist cimetidine (3.25, 6.5 or 13
      microg) showed a biphasic effect. At the lower doses (3.25 or 6.5 microg) a small
      (15%) depression of the field excitatory postsynaptic potentials and population
      spikes was observed beginning about 1 h following the infusion. At the highest
      dose tested (13 microg) a marked increase of the population spike was observed
      beginning immediately following the infusion and lasting for 90 min. Application
      of the H3 receptor agonist R-alpha-methylhistamine (0.2 microg) depressed the
      field excitatory postsynaptic potentials (15% at 4 h post-injection) and even
      more strongly the population spike (50%). Surprisingly, at higher doses (0.4 and
      0.8 microg) no effect was seen. The H3 receptor antagonist thioperamide (0.41 and
      0.82 microg) did not cause an increase in synaptic potentials but rather at the
      highest dose a small depression occurred at later time points (2-4 h following
      the infusion). At the lower dose (0.41 microg) thioperamide blocked the effect of
      R-alpha-methylhistamine (0.2 microg). These results show that the histaminergic
      system modulates information flow through the dentate gyrus in a complex manner
      involving both histamine H2 and H1 receptors.

PMID- 9579784
TI  - Inhibition of neuronal (type 1) nitric oxide synthase prevents hyperaemia and
      hippocampal lesions resulting from kainate-induced seizures.
AB  - The possible roles for nitric oxide produced by neurons in epileptic conditions
      have been investigated from two different aspects: microcirculation and delayed
      damage. Our aim was to determine whether the selective inhibition of neuronal
      (type 1) nitric oxide synthase by 7-nitroindazole, during seizures induced by
      systemic kainate, modifies hippocampal blood flow and oxygen supply and
      influences the subsequent hippocampal damage. Experiments were performed in
      conscious Wistar rats whose electroencephalogram was recorded. 7-Nitroindazole
      (25 mg/kg, i.p.) or its vehicle was injected 30 min before kainate administration
      (10 mg/kg, i.p.) and then twice at 1-h intervals. Kainate triggered typical
      limbic seizures evolving into status epilepticus, identified by uninterrupted
      electroencephalographic spike activity. The seizures were stopped by diazepam (5
      mg/kg, i.p.) after 1 h of status epilepticus. Three types of experiments were
      performed in vehicle- and 7-nitroindazole-treated rats. (1) Hippocampal nitric
      oxide synthase activity was measured under basal conditions, at 1 h after the
      onset of the status epilepticus and at 24 h after its termination (n = 4-6 per
      group). (2) Hippocampal blood flow and tissue partial pressure of oxygen were
      measured simultaneously by mass spectrometry for the whole duration of the
      experiment, while systemic variables and body temperature were monitored (n = 6
      per group). (3) Hippocampal damage was revealed by Cresyl Violet staining and
      evaluated with a lesion score seven days after status epilepticus (n = 12 per
      group). Hippocampal nitric oxide synthase activity was not significantly modified
      during status epilepticus or the following day in vehicle-treated rats. In
      contrast, it was inhibited by 57% in 7-nitroindazole-treated rats, both in basal
      conditions and after 1 h of status epilepticus, but was not different from its
      basal level 24 h later. 7-Nitroindazole significantly decreased basal hippocampal
      blood flow and tissue partial pressure in oxygen by 30% and 35%, respectively
      without affecting any systemic or thermal variable. During status epilepticus, 7
      nitroindazole significantly reduced the increase in hippocampal blood flow by 70%
      and prevented any increase in the tissue partial pressure of oxygen. Seven days
      later, the hippocampal damage in the CA1 and CA3 layers was significantly less in
      7-nitroindazole-treated rats than in vehicle-treated rats. These results indicate
      that the inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects
      neurons from seizure-induced toxicity despite reducing blood flow and oxygen
      supply to the hippocampus.

PMID- 9579785
TI  - Pituitary adenylate cyclase-activating polypeptide stimulates both c-fos gene
      expression and cell survival in rat cerebellar granule neurons through activation
      of the protein kinase A pathway.
AB  - A high density of pituitary adenylate cyclase-activating polypeptide (PACAP)
      receptors coupled to both adenylyl cyclase and phospholipase C is found in the
      external granule cell layer of the rat cerebellum during postnatal development.
      It has recently been reported that synthetic PACAP promotes cell survival and
      neurite outgrowth in immature granule cells. In the present study, we have
      investigated the transduction pathways that mediate the neurotrophic activity of
      PACAP in cultured granule cells from eight-day-old rat cerebellum. The effect of
      PACAP on cell survival was mimicked by dibutyryladenosine 3',5'-cyclic
      monophosphate but not phorbol 12-myristate 13-acetate suggesting that only the
      adenylyl cyclase pathway is involved in the neurotrophic activity of PACAP. PACAP
      also induced a transient increase in c-fos messenger RNA level. The ability of
      PACAP to stimulate c-fos gene expression was mimicked by dibutyryladenosine 3',5'
      cyclic-monophosphate but not phorbol 12-myristate 13-acetate. Similar effects of
      PACAP on granule cell survival were observed whether the cells were continuously
      incubated with PACAP for 48 h or only exposed to PACAP during 1 h. The protein
      kinase A inhibitor H89 significantly reduced the effect of PACAP on c-fos
      messenger RNA level whereas the specific protein kinase C inhibitor chelerythrine
      did not modify c-fos gene expression. These data indicate that the action of
      PACAP on cerebellar granule cell survival and c-fos gene expression are both
      mediated through the adenylyl cyclase/protein kinase A pathway. The observation
      that a short-term stimulation by PACAP can be converted into a long-lasting
      response indicates that the effect of the peptide on cell survival must involve
      immediate-early gene activation. The fact that a brief exposure to PACAP causes
      both c-fos gene expression and promotes cell survival strongly suggests that c
      fos is involved in the trophic effect of PACAP on immature cerebellar granule
      cells.

PMID- 9579786
TI  - Expression of messenger RNAs encoding ionotropic glutamate receptors in rat
      brain: regulation by haloperidol.
AB  - In situ hybridization was used to study the regional distribution of messenger
      RNAs encoding ionotropic glutamate receptor subtypes in the rat brain's
      dopaminergic cell body regions and their forebrain projection areas. Short
      oligonucleotide probes specific for the messenger RNAs encoding the flip or flop
      splice forms of the GluR1 and GluR2 AMPA (alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate) receptor subunits, or for the messenger RNAs encoding the N
      methyl-D-aspartate R1 subunit, were used. Significant differences were seen in
      the relative messenger RNA levels, and the distribution of the flip and flop
      splice forms, of GluR1 and GluR2. In the dopaminergic cell groups of the
      substantia nigra pars compacta and the ventral tegmental area, the flip form of
      both GluR1 and GluR2 dominated over the flop form. Similarly, in the core
      division of the nucleus accumbens, GluR1 and GluR2 flip forms dominated over the
      flop forms. In contrast, in the accumbens shell, the GluR1 and GluR2 flop forms
      dominated over the flip forms. As a comparison to the AMPA receptor subunits, N
      methyl-D-aspartate R1 messenger RNA was relatively evenly distributed in all the
      regions analysed. The results demonstrate a heterogeneous distribution of the
      flip and flop splice forms of GluR1 and GluR2 in the brain's dopaminergic
      pathways, which could contribute to physiological differences in regulation of
      the pathways by glutamatergic neurotransmission. We also studied regulation of
      glutamate receptor subunit expression in these regions by antipsychotic drugs,
      based on previous reports of altered levels of subunit immunoreactivity after
      drug treatment. Chronic administration of the typical antipsychotic drug,
      haloperidol, caused a small but significant induction of GluR2 flip messenger RNA
      in the dorsolateral caudate putamen. This effect was not seen after chronic
      administration of the atypical antipsychotic drug, clozapine. Significant drug
      regulation of the other glutamate receptor subunits studied was not observed.

PMID- 9579787
TI  - Regional distribution of [35S]2'-deoxy 5'-O-(1-thio) ATP binding sites and the
      P2Y1 messenger RNA within the chick brain.
AB  - The distribution of the P2Y1 receptor protein and transcript in the one-day-old
      chick brain were determined by quantitative in vitro ligand autoradiography and
      in situ hybridization histochemistry. We have previously used [35S]2'-deoxy 5'-O
      (1-thio) ATP as a radioligand for the recombinant P2Y1 receptor transiently
      expressed in COS-7 cells and have also shown that such sites are present at high
      density (Bmax: approximately 37 pmol radioligand bound/mg protein) in chick brain
      membranes. Here we report the macroscopic localization of these [35S]2'-deoxy 5'
      O-(1-thio) ATP binding sites within the chick brain. They were found to be widely
      distributed there (within the range of 0.047 +/- 0.012 to 0.309 +/- 0.035 pmol
      bound/mg wet tissue). The affinities of P2 agonists and antagonists at these
      binding sites was comparable to that found previously for the recombinant P2Y1
      receptor. In parallel experiments, the regional and cellular localization of the
      P2Y1 receptor messenger RNA was examined by in situ hybridization. The transcript
      was also found to be widely distributed throughout the brain. High levels of
      hybridization were detected in the cortex piriformis, ectostriatum, hippocampus,
      cerebellum and in a range of discrete nuclei throughout the brain, including the
      ovoidalis, isthmo-opticus and spiriformis lateralis nuclei. Localization at
      cellular level indicates that this receptor transcript is expressed in neurons
      and also at non-neuronal sites. Furthermore, the distribution of the P2Y1
      transcript and the [35S]2'-deoxy 5'-O-(1-thio) ATP binding sites matched in a
      number of the regions and structures mentioned above. The present study clarifies
      the anatomical distribution of the P2Y1 receptor within the chick brain. Its
      broad distribution coupled with its neuronal expression suggest an important role
      for this type of metabotropic nucleotide receptor within the brain.

PMID- 9579788
TI  - Adrenergic innervation of the monkey thalamus: an immunohistochemical study.
AB  - The distribution and function of the neurotransmitter adrenaline in the primate
      brain are poorly understood. Biochemical studies have shown the presence of
      adrenaline or its biosynthetic enzyme, phenylethanolamine-N-methyltransferase, in
      the rat and human thalamus. However, the distribution of the adrenergic fibres in
      the thalamus has only been demonstrated in rats. We study the adrenergic
      innervation of the macaque monkey thalamus using immunohistochemistry against
      phenyletanolamine-N-methyltransferase. The distribution of phenyletanolamine-N
      methyltransferase-immunoreactive fibres is markedly heterogeneous and principally
      restricted to those nuclei, or their portions, that are located in or close to
      the midline, with the highest density being found in the paraventricular,
      parafascicular and mediodorsal nuclei. The paraventricular nucleus is densely
      innervated by adrenergic axons throughout, while the densest innervation of the
      parafascicular nucleus is located in its medial part and the strongest
      mediodorsal nuclear immunolabelling is found in its most posterior and medial
      region. Moderate or low concentrations of phenyletanolamine-N-methyltransferase
      immunopositive fibres are present in the paratenial nucleus, and all parts of the
      central nucleus, nucleus reuniens, central medial nucleus, centromedian nucleus,
      medial geniculate body and medial pulvinar nucleus, while only scattered
      immunoreactive axons are found in other thalamic nuclei. The morphology of the
      phenyletanolamine-N-methyltransferase-immunoreactive axons is quite diverse, as
      they have different diameters and most are endowed with diversely-shaped
      varicosities. These findings are the first morphological evidence for the
      presence of adrenergic innervation in the primate thalamus and reveal that this
      innervation is highly selective, heterogeneous and more widely distributed in
      primates than in rats. The thalamic nuclei innervated by adrenaline are connected
      to widespread limbic and associative cortical areas as well as to subcortical
      structures, in particular the neostriatum and amygdala. We hypothesize that
      thalamic adrenaline may be implicated in emotional, social and attentional
      mechanisms through its facilitation of co-ordinated action by these brain
      regions.

PMID- 9579789
TI  - Olfaction in rats with extensive lesions of the olfactory bulbs: implications for
      odor coding.
AB  - Rats were initially trained on a series of odor detection tasks and then received
      a unilateral olfactory bulbectomy and removal of different parts of the
      contralateral bulb. After postoperative recovery they were tested for detection
      of different concentrations of four odors, on a series of odor discrimination
      tasks and for their ability to acquire a relatively easy and a more difficult
      odor mixture discrimination task. Groups were formed based on which region of the
      bulb was intact (regional savings score) and on amount of bulb intact (bulbar
      savings score). In general, only rats with bulbar savings scores of less than 21%
      had deficits in detection or discrimination tasks but most performed as well as
      controls in most tasks. Correlations between bulbar savings scores and error
      scores were relatively low across all rats but, within the subgroup with the
      largest lesions (bulbar savings scores <21%), high correlations between these
      variables were obtained. There was no evidence for a specific anosmia in any
      group or individual rat and, except for the more difficult odor mixture
      discrimination, no one task proved difficult for any subgroup. The present
      results demonstrate that rats with relatively small remnants of one olfactory
      bulb can perform a variety of odor detection and discrimination tasks as well or
      nearly as well as controls. These outcomes provide no support for localization of
      function within the olfactory bulb but are in accord with recent proposals that
      odors may be coded by a highly distributed pattern of bulbar input.

PMID- 9579790
TI  - Early specification of striatal projection neurons and interneuronal subtypes in
      the lateral and medial ganglionic eminence.
AB  - The striatum is thought to be generated from two transient swellings in the
      ventral telencephalon, the lateral and medial ganglionic eminences, present at
      mid-stages of embryonic rat development. We have studied the relative
      contribution of these structures to the specific generation of striatal neuronal
      subtypes such as projection neurons and cholinergic and somatostatin-containing
      interneurons at an early stage and a mid stage in striatal neurogenesis.
      Dissociated progenitors isolated from the embryonic day 12.5 and embryonic day
      15.5 rat lateral ganglionic eminence grafted into the previously ibotenic acid
      lesioned adult striatum, produce grafts containing extensive numbers of neurons
      expressing messenger RNA for the striatal projection neuron marker, DARPP-32,
      whereas grafts of the embryonic day 12.5 and embryonic day 15.5 medial ganglionic
      eminences do not. While preprosomatostatin messenger RNA-expressing neurons were
      observed in grafts from each of the lateral ganglionic eminence and medial
      ganglionic eminence at both embryonic day 12.5 and embryonic day 15.5, choline
      acetyltransferase messenger RNA-expressing cholinergic neurons were largely found
      in grafts derived from the embryonic day 12.5 medial ganglionic eminence. These
      results suggest that the neuronal diversity of the adult striatum may derive both
      from the lateral ganglionic eminence, providing DARPP-32-expressing projection
      neurons as well as somatostatin-containing interneurons, and the early stage
      medial ganglionic eminence specifically contributing the cholinergic
      interneurons.

PMID- 9579791
TI  - Interaction of calcium-permeable non-N-methyl-D-aspartate receptor channels with
      voltage-activated potassium and calcium currents in rat retinal ganglion cells in
      vitro.
AB  - Calcium-permeable non-N-methyl-D-aspartate receptor channels are now
      characterized in much detail, but still little is known about the consequences of
      Ca2+ influx through these channels in specific neuron types. We are interested in
      the role of Ca2+-permeable non-N-methyl-D-aspartate receptor channels during
      differentiation of retinal ganglion cells. However, in view of the conflicting
      data on the relative Ca2+ permeability of non-N-methyl-D-aspartate receptor
      channels in these neurons, a more systematic evaluation of permeation properties
      of different Na+ substitutes was necessary before proceeding with the main goal
      of the present study evaluating the effects of non-N-methyl-D-aspartate receptor
      activation on repetitive firing and voltage-activated K+ and Ca2+ conductances.
      Retinal ganglion cells were dissociated from the rat retina on postnatal day 5.
      They were selected by vital anti-Thy-1 immunostaining and repetitive firing
      behaviour and submitted to patch-clamp recording in the whole-cell configuration.
      Non-N-methyl-D-aspartate receptor channels were activated by application of amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate. It was found that they
      were essentially impermeable to N-methyl-D-glucamine (P(NMDG)/P(Cs)<0.02), but
      not to choline (P(choline)/P(Cs)=0.24) and tetramethylammonium
      (P(TMA)/P(Cs)=0.23). When using N-methyl-D-glucamine as a substitute for Na+ to
      obtain bi-ionic conditions P(Ca)/P(Cs) varied between 0.08 to 1.40. Linear
      current voltage relation or little outward rectification corresponded to a low
      Ca2+ permeability (P(Ca)/P(Cs)=0.14). In about one third of the cells kainate
      induced currents showed inward rectification and non-N-methyl-D-aspartate
      receptor agonists induced a substantially higher Ca2+ influx (P(Ca)/P(Cs)=0.64).
      Activation of non-N-methyl-D-aspartate receptors by kainate profoundly altered
      the repetitive discharge of retinal ganglion cells. In contrast to the
      continuously firing controls, cells generated only a few spikes at the beginning
      of a steady depolarization after kainate exposure. Among the candidates
      regulating the firing behaviour of retinal ganglion cells voltage-activated Ca2+
      and K+ conductances were tested for their sensitivity to kainate application. It
      was found that even short conditioning pulses of kainate decreased the peak
      amplitudes of both voltage-activated K+ and voltage-activated Ca2+ currents. Only
      the latter effect required extracellular Ca2+ and was antagonized by increasing
      the intracellular Ca2+ buffering strength. Thus, suppression of calcium currents
      was induced by a non-N-methyl-D-aspartate receptor-mediated rise of the
      intracellular calcium concentration. The reduction of K+ currents did not depend
      on extracellular calcium and was insensitive to experimental manipulation of
      intracellular Ca2+ buffer strength. The interaction between Ca2+-permeable non-N
      methyl-D-aspartate receptor channels and voltage-activated Ca2+ and K+ currents
      may represent an important regulatory mechanism to control the repetitive firing
      of developing retinal ganglion cells.

PMID- 9579792
TI  - Subcellular localization of preprogalanin messenger RNA in perikarya and axons of
      hypothalamo-posthypophyseal magnocellular neurons: an in situ hybridization
      study.
AB  - The subcellular compartmentalization and axonal transport of oxytocin and
      vasopressin messenger RNAs have recently been reported in the rat hypothalamo
      posthypophyseal system using in situ hybridization. So far, no data are available
      concerning the intracellular distribution of co-localized peptide transcripts,
      for example of galanin, which is synthesized in the vasopressinergic
      magnocellular neurons of the rat and which is up-regulated in these neurons under
      different conditions, including salt loading and colchicine injection. In the
      present study, using non-radioactive in situ hybridization and
      immunohistochemistry at the light and electron microscope levels, preprogalanin
      messenger RNA and galanin-like immunoreactivity were localized in the hypothalamo
      posthypophyseal system. After salt loading, preprogalanin transcripts were found
      throughout the perikaryal cytoplasm, especially in the peripheral cytoplasm and
      in the perinuclear area. Since immunohistochemistry also showed galanin-like
      immunoreactivity preferentially in the perinuclear area of control rats, galanin
      synthesis may occur mainly in this cytoplasmic domain. Preprogalanin messenger
      RNA was also clustered in dendrites containing rough endoplasmic reticulum. The
      use of a new in situ hybridization method involving tyramide signal
      amplification, based on catalysed reporter deposition, allowed visualization of
      preprogalanin messenger RNA in axonal projections running through the internal
      layer of the median eminence after salt loading, but not in control or in
      colchicine-injected animals. The negative results obtained after colchicine
      injection indicate that the mechanism of messenger RNA transport may require an
      intact cytoskeleton. The labelling was found in non-dilated axon segments as well
      as in a subset of axonal swellings in the rostral aspect of the median eminence,
      but was restricted to a few swellings in its caudal part, with no labelling in
      the posterior pituitary. Thus, preprogalanin messenger RNA was segregated in the
      axons. The functional significance of messenger RNAs' exportation into axons is
      not known, but our results suggest that this phenomenon may not be limited to the
      two principal magnocellular hormone messenger RNAs, but may also involve co
      existing peptide messenger RNAs.

PMID- 9579793
TI  - Inhibition of rat oxytocin and vasopressin supraoptic nucleus neurons by
      nociceptin in vitro.
AB  - The effects of nociceptin (orphanin FQ) on the excitability of
      electrophysiologically-identified oxytocin and vasopressin neurons were
      investigated in rat hypothalamic supraoptic nucleus slices in vitro, using whole
      cell patch-clamp recording techniques. Nociceptin inhibited the spontaneous
      discharge of 9/20 (45%) of supraoptic nucleus neurons tested, while in the
      remaining 11/20 neurons it inhibited firing rate and induced repetitive burst
      firing. There were no differences between the effects of nociceptin on oxytocin
      and vasopressin neurons. When recordings were made using EGTA-containing patch
      pipettes, nociceptin caused inhibition in all 30 supraoptic nucleus neurons
      tested, and burst-firing was not seen. The inhibitory effects of nociceptin
      persisted in low Ca, Co medium, and were not antagonized by naloxone at
      concentrations sufficient to antagonize the inhibitory actions of morphine and
      U50488. The actions of nociceptin on supraoptic nucleus neurons are therefore
      likely to be mediated by postsynaptic opioid receptor-like (ORL1) receptors that
      are distinct from known opioid receptors. The inhibitory responses to nociceptin
      were also insensitive to naloxone benzoylhydrazone, which itself had no effect on
      the spontaneous discharge of the supraoptic nucleus neurons. Our findings
      demonstrate that endogenous nociceptin may have a functional role in regulating
      oxytocin and vasopressin secretion through its actions on hypothalamic supraoptic
      nucleus neurons.

PMID- 9579794
TI  - An assessment of the effects of central interleukin-1beta, -2, -6, and tumor
      necrosis factor-alpha administration on some behavioural, neurochemical,
      endocrine and immune parameters in the rat.
AB  - Despite a vast amount of research into the actions of cytokines within the
      central nervous system, the pharmacological role and/or physiological function of
      the various cytokines within the central nervous system is still not fully
      understood. The present study evaluated the effects of intracerebroventricular
      administration of interleukin-1beta, -2, -6 (20 ng) and tumour necrosis factor
      alpha (40 ng) on elevated plus maze behaviour, monoamine levels in the
      hypothalamus, hippocampus and amygdala, plasma corticosterone and catecholamine
      concentrations and Concanavalin A-induced splenic lymphocyte proliferation in the
      rat. Both interleukin-1beta and tumour necrosis factor-alpha induced "anxiogenic
      like" effects on the elevated plus maze, whereas interleukin-2 and interleukin-6
      did not. However only interleukin-1beta led to endocrine variations often
      associated with stress and anxiety. Cytokine specific alterations in monoamine
      levels were evident in the hypothalamus and hippocampus, while neurotransmitter
      concentrations in the amygdala were not significantly altered by cytokine
      treatment. In addition, interleukin-1beta reduced Concanavalin A-induced
      lymphocyte proliferation, whereas the other cytokine treatments failed to
      significantly alter this response. These results demonstrate that in some, but
      not all, respects interleukin-1beta administration produced "stress like" effects
      on behaviour, monoamine neurotransmitters, hypothalamic pituitary adrenal axis
      activity and immune function, while the other cytokines produced less consistent
      effects on these parameters. It is noteworthy that although interleukin-1beta and
      tumour necrosis factor-alpha provoked an anxiogenic response in the elevated plus
      maze test of anxiety, neither cytokine significantly altered amygdaloid
      noradrenergic or serotonergic activity, as many previous studies have implicated
      increased amygdaloid noradrenergic and/or serotonergic activity in the
      pathophysiology of anxiety.

PMID- 9579795
TI  - CNS location of uterine-related neurons revealed by trans-synaptic tracing with
      pseudorabies virus and their relation to estrogen receptor-immunoreactive
      neurons.
AB  - Retrograde, transneuronal tracing with Bartha's strain of pseudorabies virus was
      used in rats to identify spinal cord, brainstem and hypothalamic loci of uterine
      related neurons that could function in the regulation of uterine activity. Based
      on the premise that estrogen might influence such uterine-related neurons, the
      existence of estrogen receptors in neurons in these same loci was examined. Viral
      injections were made into the uterine cervix, body and cervical end of the
      uterine horns, and the rats allowed to survive for four to six days. After four
      days, mainly the spinal cord, medulla and pons contained virus-infected neurons.
      After longer survival times, progressively higher levels of the neuraxis
      contained viral-labeled neurons, so that by six days hypothalamic uterine-related
      neurons were identified. First-order virus-infected neurons were visualized by
      immunohistochemistry in the pelvic paracervical parasympathetic ganglia and in
      inferior mesenteric sympathetic ganglia. Preganglionic and putative interneurons
      were labeled in the lumbosacral spinal cord and thoracic spinal cord mainly in
      the lateral horn area (sacral parasympathetic nucleus and intermediolateral
      nucleus), lateral aspect of the dorsal horn, intermediate gray, lamina X and
      dorsal gray commissural area. In the brainstem, labeling was most evident and
      consistent in the nucleus tractus solitarius, ventrolateral medulla, raphe magnus
      and pallidus nuclei, parapyramidal area, A5 cell group, Barrington's nucleus of
      the pons and periaqueductal gray of the midbrain. In the hypothalamus, virus
      infected neurons were most marked in the paraventricular nucleus, with fewer in
      the medial preoptic area and ventromedial hypothalamic nucleus. Estrogen receptor
      immunoreactive neurons were most often present among the virus-labeled uterine
      related neurons of the spinal cord, nucleus tractus solitarius, ventrolateral
      medulla, periaqueductal gray, medial preoptic area and ventromedial hypothalamic
      nucleus. These results identify a multisynaptic pathway of neurons whose eventual
      output is involved in uterine functions, whose distribution is similar to that
      revealed by pseudorabies virus tracing from other visceral organs, and which are
      often mixed among estrogen-responsive neurons.

PMID- 9579796
TI  - Alterations in information transmission in ensembles of primary muscle spindle
      afferents after muscle fatigue in heteronymous muscle.
AB  - This study showed that fatigue of the ipsilateral medial gastrocnemius muscle
      caused a clear-cut reduction in the ability of ensembles of primary muscle
      spindle afferents from the lateral gastrocnemius muscle to discriminate between
      muscle stretches of varying amplitude. The results were probably caused by reflex
      mediated effects from chemosensitive group III and IV afferents onto the gamma
      motoneurons projecting to lateral gastrocnemius muscle spindles. The experiments
      were conducted on seven cats anaesthetized with alpha-chloralose and a total of
      41 primary muscle spindle afferents from the lateral gastrocnemius were
      registered. Afferents were simultaneously recorded in ensembles of three to 10
      afferents. A method based on principal component analysis and algorithms for
      quantification of stimulus discrimination in ensembles of muscle afferents was
      used prior to, immediately following and five or more minutes after muscle
      fatigue had been induced to the ipsilateral medial gastrocnemius muscle. It is
      well established that the primary muscle spindle afferents play an important role
      in proprioception and kinaesthesia. Therefore the decrease in the accuracy of the
      information transmitted by ensembles of primary muscle spindle afferents caused
      by fatigue in an ipsilateral muscle implies concomitant effects on proprioception
      and kinaesthesia.

PMID- 9579797
TI  - Computational carbohydrate chemistry: what theoretical methods can tell us.
AB  - Computational methods have had a long history of application to carbohydrate
      systems and their development in this regard is discussed. The conformational
      analysis of carbohydrates differs in several ways from that of other
      biomolecules. Many glycans appear to exhibit numerous conformations coexisting in
      solution at room temperature and a conformational analysis of a carbohydrate must
      address both spatial and temporal properties. When solution nuclear magnetic
      resonance data are used for comparison, the simulation must give rise to ensemble
      averaged properties. In contrast, when comparing to experimental data obtained
      from crystal structures a simulation of a crystal lattice, rather than of an
      isolated molecule, is appropriate. Molecular dynamics simulations are well suited
      for such condensed phase modeling. Interactions between carbohydrates and other
      biological macromolecules are also amenable to computational approaches. Having
      obtained a three-dimensional structure of the receptor protein, it is possible to
      model with accuracy the conformation of the carbohydrate in the complex. An
      example of the application of free energy perturbation simulations to the
      prediction of carbohydrate-protein binding energies is presented.

PMID- 9579798
TI  - A novel and efficient method for synthetic carbohydrate conjugate vaccine
      preparation: synthesis of sialyl Tn-KLH conjugate using a 4-(4-N-maleimidomethyl)
      cyclohexane-1-carboxyl hydrazide (MMCCH) linker arm.
AB  - STn (NeuAcalpha2 --> 6GalNAc alpha-O-Ser/Thr) is a carbohydrate epitope
      overexpressed in various human carcinomas. Clinical trials are underway using
      synthetic STn or STn trimeric glycopeptides [STn, cluster; STn(c)] conjugated
      with keyhole limpet hemocyanin (KLH) as active specific immunotherapy for these
      cancers. These vaccines have been prepared by conjugating a crotyl ethyl amide
      derivative of STn or STn(c) to KLH by direct reductive amination after
      ozonolysis. In the case of STn(c) the conjugation efficiency and the resulting
      epitope ratios were low. This may be due to steric hinderance of the short spacer
      arm. To overcome these difficulties, without resynthesis, the STn(c) glycopeptide
      was modified by attachment of an MMCCH (4-(4-N-maieimidomethyl) cyclohexane-1
      carboxyl hydrazide) spacer arm to the aldehyde derivative, and then conjugated
      with thiolated KLH. This method gave a higher epitope ratio and yield than the
      direct method. The STn(c)-MMCCH-KLH conjugate induced high titer antibodies in
      mice against STn(c). This method may be generally applicable for large synthetic
      oligosaccharides.

PMID- 9579799
TI  - Convergent synthesis of neoglycopeptides by coupling of 2-bromoethyl glycosides
      to cysteine and homocysteine residues in T cell stimulating peptides.
AB  - The 2-bromoethyl beta-glycosides of the disaccharide galabiose [Gal(alpha1-4)Gal]
      and the trisaccharides globotriose [Gal(alpha1-4)Gal(beta1-4)Glc] and 3'
      sialyllactose [Neu5Ac(alpha2-3)Gal(beta1-4)Glc] have been prepared by improved
      routes. The 2-bromoethyl glycosides were then used in cesium carbonate promoted
      alkylations of the sulfhydryl groups of cysteine and homocysteine residues in T
      cell stimulating peptides. This convergent and general approach was used to
      prepare 16 neoglycopeptides which were obtained in 52-95% yields after
      purification by HPLC. 1H NMR spectroscopy revealed that beta-elimination and
      epimerization of neoglycopeptide stereocentres did not occur during the
      synthesis.

PMID- 9579800
TI  - Identification, expression and tissue distribution of cytidine 5'-monophosphate N
      acetylneuraminic acid synthetase activity in the rat.
AB  - We report the postnatal developmental profiles of N-acetylneuraminic acid
      cytidylyltransferase (EC 2.7.7.43) (CMP-Neu5Ac synthetase) in different rat
      tissues. This enzyme, which catalyses the activation of NeuAc to CMP-Neu5Ac, was
      detected in brain, kidney, heart, spleen, liver, stomach, intestine, lung,
      thymus, prostate and urinary bladder but not in skeletal muscle. Comparative
      analysis of the different specific activity profiles obtained shows that the
      expression of CMP Neu5Ac synthetase is tissue-dependent and does not seem to be
      embryologically determined. Changes in the level of sialylation during
      development were also found to be intimately related to variations in the
      expression of this enzyme, at least in brain, heart, kidney, stomach, intestine
      and lung.

PMID- 9579801
TI  - Characterization of a mouse monoclonal IgG3 antibody to the tumor-associated
      globo H structure produced by immunization with a synthetic glycoconjugate.
AB  - Globo H (Fuc alpha1 --> 2Galbeta1 --> 3GalNAcbeta1 --> 3Gal alpha1 --> 4Galbeta1 
      -> 4Glc) is a carbohydrate structure that shows enhanced expression in many human
      carcinomas. From mice immunized with a globo H-KLH (keyhole limpet hemocyanin)
      synthetic conjugate an IgG3 monoclonal antibody (mAb VK-9) was derived that
      recognizes the globo H structure. Serological analysis showed that the minimal
      structure recognized by this mAb was the tetrasaccharide sequence Fuc alpha1 -->
      2Galbeta1 --> 3GalNAcbeta1 --> 3Gal. An isomeric structure with an internal
      alphaGalNAc linkage was also recognized but less efficiently. mAb VK-9 did not
      react with many related structures, such as galactosylgloboside, globoside, H
      type 1, H type 2 blood group structures or fucosyl-gangliotetraosyl ceramide, but
      did react weakly with globo A ceramide. Not only did mAb VK-9 react with
      carbohydrate-protein conjugates but it could also recognize globo H-ceramide and
      human tumor cells expressing globo H. These results suggest that globo H-KLH
      could be explored as a vaccine in the treatment of carcinoma patients.

PMID- 9579802
TI  - Effect of shape, size, and valency of multivalent mannosides on their binding
      properties to phytohemagglutinins.
AB  - Clusters of di-, tri-, and tetra-antennary alpha-D-mannopyranosides were
      synthesized in good yields based on the coupling of amine-bearing mono- or
      trisaccharide [Man alpha(1 --> 6)[Man alpha(1 --> 3)]Man] haptens to poly
      isocyanate or -isothiocyanate tethering cores. The relative binding properties of
      the resulting multivalent ligands were determined by turbidimetric and solid
      phase enzyme-linked lectin assays (ELLA) using plant lectins
      (phytohemagglutinins) Concanavalin A (Con A) and Pisum sativum (pea lectin)
      having four and two carbohydrate binding sites, respectively. Rapid and efficient
      cross-linking between tetravalent Con A and mannopyranosylated clusters were
      measured by a microtiter plate version of turbidimetric analyses. In inhibition
      of binding of the lectins to yeast mannan, the best tetravalent monosaccharide
      (30) and trisaccharide (31) inhibitors were shown to be 140 and 1155 times more
      potent inhibitors than monomeric methyl alpha-D-mannopyranoside against pea
      lectin and Con A, respectively. Compounds 30 and 31 were thus 35- and 289-fold
      more potent than the reference monosaccharide based on their hapten contents. As
      a general observation, the ligands bearing the Man alpha(1 --> 6)[Man alpha(1 -->
      3)]Man trimannoside structures were found to be more potent inhibitors for Con A
      than the ligands having single mannoside residues, whereas pea lectin could not
      discriminate between the two types of ligands.

PMID- 9579804
TI  - Influence of the amino acid sequence on the MUC5AC motif peptide O-glycosylation
      by human gastric UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase(s).
AB  - The present work was carried out to study the role of the peptide moiety in the
      addition of O-linked N-acetylgalactosamineto human apomucin using human crude
      microsomal homogenates from gastric mucosa (as enzyme source) and a series of
      peptide acceptors representative of tandem repeat domains deduced from the MUC5AC
      mucin gene (expressed in the gastric mucosa). Being rich in threonine and serine
      placed in clusters, these peptides provided several potential sites for O
      glycosylation. The glycosylated products were analysed by a combination of
      electrospray mass spectrometry and capillary electrophoresis in order to isolate
      the glycopeptides and to determine their sequence by Edman degradation. The O
      glycosylation of our MUC5AC motif peptides gave information on the specificity
      and activity of the gastric microsomal UDP-N-acetylgalactosamine:polypeptide N
      acetylgalactosaminyltransferase(s). The proline residues and the induced
      conformations are of great importance for the recognition of MUC5AC peptides but
      they are not the only factors for the choice of the O-glycosylation sites.
      Moreover, for the di-glycosylated peptides, the flanking regions of the proline
      residues strongly influence the site of the second O-glycosylation.

PMID- 9579803
TI  - Determination of glycan structures and molecular masses of the glycovariants of
      serum transferrin from a patient with carbohydrate deficient syndrome type II.
AB  - Serum transferrin from a child with carbohydrate deficient syndrome type II was
      isolated by immunoaffinity chromatography and separated into minor and major
      fractions by fast protein liquid chromatography. The structure of the glycans
      released from the major fraction by hydrazinolysis was established by application
      of methanolysis and 1H-NMR spectroscopy. The results led to the identification of
      an N-acetyllactosamininic type monosialylated, monoantennary Man(alpha1-3) linked
      glycan. By electrospray-mass spectrometry analysis, the whole serum transferrin
      was separated into at least seven species (I to VII) with molecular masses
      ranging from 77,958 to 79,130 Da. On the basis of a polypeptide chain molecular
      mass of 75,143 Da, it was calculated that the major transferrin species III
      (78,247 Da) contains two monosialylated monoantennary glycans. The molecular mass
      of transferrin species V and VI (78,678 and 78,971 Da) suggests that one of their
      two glycans contains an additional N-acetyllactosamine and a sialylated N
      acetyllactosamine units, respectively. Transferrin species I and V were found to
      correspond to the desialylated forms of species III and VI. The abnormal glycan
      structures can be explained by a defect in the N-acetylglucosaminyltransferase II
      activity [Charuk et al. (1995) Eur J Biochem 230: 797-805].

PMID- 9579805
TI  - Heterogeneity in the protein cores of mucins isolated from human middle ear
      effusions: evidence for expression of different mucin gene products.
AB  - High molecular weight mucins were isolated and purified from human middle ear
      effusions of children with Otitis Media with Effusion (OME) classified into three
      groups, (1) thick and (2) thin from anatomically normal children and (3)
      effusions from cleft palate patients. Amino acid analyses of the purified mucins
      from the three pools were similar but not identical with characteristic contents
      of serine threonine and proline (32%, 28%, and 38% for pools (1) (2) and (3)
      respectively). Proteinase resistant glycopeptide fragments corresponding to the
      tandem repeat domains of cloned mucin genes showed marked differences both
      between the three mucin pools and with the composition of the tandem repeat
      sequences of the cloned mucin genes expressed in the airways. Studies on the
      antigenic identity of middle ear mucins found an epitope likely to be present on
      MUC5AC, but only accounting for a maximum of 15% by weight and no reactivity was
      found with antibodies to MUC2 or MUC1. A polyclonal antibody raised to thick
      effusion mucins reacted strongly with human salivary mucin suggesting the
      presence of MUC5B epitopes. These studies suggest that more than one mucin gene
      product is secreted by the human middle ear mucosa and that there may be further
      mucin genes expressed by the middle ear that have yet to be cloned.

PMID- 9579806
TI  - A molecular modelling study of the interaction between beta-cyclodextrin and the
      organophosphorothioate pesticide parathion.
AB  - The interaction between parathion and beta-cyclodextrin was investigated by
      Molecular Dynamics. Several in vacuo trajectories were calculated for the system
      imposing a 1:1 stoichiometry. The influence of the solvent and temperature was
      considered. The results account for the formation of adducts which are stable at
      room temperature and involve mainly the nitrophenoxy group of the guest molecules
      which interacts with the hydrophobic cavity of the host by van der Waals forces.

PMID- 9579807
TI  - Interaction of Ca2+ and Na+ ions with polygalacturonate chains: a molecular
      dynamics study.
AB  - Partially esterified polygalacturonic acid is the main component of pectin in
      higher plants. The carboxylic groups and their methyl esters markedly affect the
      ability of the pectin molecules to bind oppositely charged ions and to form gels.
      In order to make a contribution to the understanding of the mechanisms which
      regulate the ionic transfer at the soil-root interface and in the apoplast, we
      report the results of a set of molecular dynamics experiments in which the
      interactions of four fully deprotonated fragments of polygalacturonic acid, each
      counting 12 units, 300 water molecules and 48 or 24 Na+ and Ca2+ ions were
      studied. We observed the formation of Ca2+ bridges between the polygalacturonate
      chains. The forces driving the aggregation processes are characterized by the
      formation of strong coulombic interactions between the metal ions and the
      carboxylate groups. The results are consistent with experiment evidence of the
      formation of Ca-polygalacturonate organized gels. The Ca-polygalacturonate
      complex exhibits a lower energy compared to that of Na-polygalacturonate. The
      ratio of the Na+ and Ca2+ diffusion coefficients agree well with experimental
      reports.

PMID- 9579809
TI  - Solution conformation and dynamics of a fungal cell wall polysaccharide isolated
      from Microsporum gypseum.
AB  - The conformational and dynamical features of a branched mannan isolated from a
      fungal cell wall have been analysed by homo and heteronuclear NMR methods,
      employing different magnetic fields. 1H NMR cross relaxation times have been
      obtained for this polysaccharide and have been interpreted qualitatively using
      different motional models. 13C NMR relaxation parameters (T1, T2, NOE) have also
      been measured and interpreted using different approximations based on the Lipari
      and Szabo model free approach. The analysis of the data indicate the existence of
      important flexibility for the different linkages of the polysaccharide. Motions
      in the range of 4-6 ns contribute to the relaxation of the macromolecule,
      although faster internal motions in the 500 ps and 100 ps timescales are also
      present. These time scales indicate that segmental motions as well as internal
      motions around the glycosidic linkages are the major sources of relaxation for
      this molecule at 318 K. Molecular dynamics simulations have also been performed.
      The obtained results also indicate that the polysaccharide possess a substantial
      amount of conformational freedom.

PMID- 9579808
TI  - Transcriptional regulation of the human UDP-GlcNAc:alpha-6-D-mannoside beta-1-2-N
      acetylglucosaminyltransferase II gene (MGAT2) which controls complex N-glycan
      synthesis.
AB  - UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase II (GnT
      II; EC 2.4.1.143) is essential for the normal assembly of complex Asn-linked
      glycans. Northern analysis showed a major transcript at 2.0 kb and a minor band
      at approximately 2.9 kb in five different human cell lines. The gene (MGAT2) has
      three AATAAA polyadenylation sites at 68, 688 and 846 bp downstream of the
      translation stop codon. 3'-RACE (rapid amplification of cDNA ends) using RNA from
      the human cell line LS-180 indicated that all three sites were utilized for
      transcription termination. 5'-RACE and RNase protection analyses showed multiple
      transcription initiation sites at -440 to -489 bp relative to the ATG translation
      start codon (+1). The data show that the entire GnT II gene is on a single exon.
      The gene has a CCAAT box at -587 bp but lacks a TATA box and the 5'-untranslated
      region is GC-rich and contains consensus sequences suggestive of multiple binding
      sites for Sp1; these properties are typical for housekeeping genes. A series of
      chimeric constructs containing different lengths of the 5'-untranslated region
      fused to the chloramphenicol acetyltransferase (CAT) reporter gene were tested in
      transient transfection experiments using HeLa cells. The CAT activity of the
      construct containing the longest insert (-1076 bp relative to the ATG start
      codon) showed a approximately 38-fold increase as compared to that of the
      control. Removal of the region between -636 and -553 bp caused a dramatic
      decrease in CAT activity indicating this to be the main promoter region of the
      gene.

PMID- 9579810
TI  - Clinical outcome of patients undergoing multivessel coronary stent implantation.
AB  - OBJECTIVES: To evaluate the outcome of patients undergoing multivessel coronary
      stent implantation. BACKGROUND: Percutaneous transluminal coronary angioplasty
      has been shown to be an effective treatment for multivessel coronary artery
      disease, although the need for repeat revascularization continues to be a
      limitation. Intracoronary stent placement has been shown to reduce the need for
      subsequent revascularization. METHODS: Seventy-seven patients without prior
      coronary artery bypass grafting (CABG) undergoing multivessel coronary
      revascularization in which stents were placed in all treated segments over a 5
      year period at our institution were identified. Clinical and angiographic
      characteristics and outcomes were analyzed. RESULTS: One hundred and eighty-eight
      coronary lesions were successfully treated (2.1+/-0.3 treated vessels/patient,
      2.4+/-0.6 treated lesions/patient) using 2.8+/-1.2 stents/patient (range 2-9) and
      1.4+/-0.8 stents/vessel (range 1-6). Procedural success rate [angiographic
      success without in-hospital death, Q-wave myocardial infarction (Q-wave MI) or
      CABG] was achieved in 76 of 77 patients (98.7%). Anatomically complete
      revascularization was achieved in 46 (59.7%) patients. Modified ACC/AHA Type B2
      and C lesions comprised 75.5% of the 188 lesions. The left anterior descending
      artery was treated in 57 (74.0%) patients. The indication for stent placement was
      dissection or threatened/abrupt closure in 54 segments (28.8%). In-hospital
      events included death in one patient (1.3%); no patient suffered a Q-wave MI or
      required CABG. Stent occlusion occurred in two (2.6%) patients, and repeat
      percutaneous intervention of the target vessel was also required in these two
      patients. Any of these adverse events occurred in three (3.9%) patients. No
      further events occurred after hospital discharge in the 30 days after the
      procedure. Of hospital survivors (n=76), adverse events at 6 months included
      death in two patients (2.6%), MI in two (2.6%), CABG in six (7.9%); nine (11.8%)
      patients underwent repeat percutaneous intervention and 15 (19.7%) underwent any
      revascularization. CONCLUSIONS: Multivessel coronary stent placement is
      associated with an excellent procedural success rate despite a high rate of
      adverse lesion characteristics, and a low rate of death or MI during follow-up.
      The need for further revascularization compares favorably with published rates
      with multivessel PTCA and single stent implantation for discrete de novo lesions.

PMID- 9579811
TI  - Ethnic differences in expression of susceptibility marker(s) in rheumatic
      fever/rheumatic heart disease patients.
AB  - The ability of monoclonal antibodies (MAb) against a human B lymphocyte
      alloantigen has been suggested to discriminate between rheumatic fever
      "susceptible" individuals and persons with a lower risk of developing RF.
      However, while such MAb have been reported to identify a majority of RF/RHD
      patients in some populations, a reduced discriminatory ability has been observed
      in others. Antigenic variation in the RF marker(s) may exist among ethnic groups
      which reduce the discriminatory ability of these monoclonal antibodies. We
      developed MAb using B lymphocytes from RF patients of North Indian ethnic origin.
      In this same population we compared the new MAb (PGI/MN II) with a previously
      described MAb of Caucasian ethnic origin (D8/17). In three groups: acute
      rheumatic fever patients (no evidence of previous attacks of rheumatic fever),
      patients with chronic rheumatic heart disease and normal controls from the same
      population, we found a greater discriminating ability of PGI/MNII MAb to identify
      Indian RF/RHD patients than with the D8/17 MAb. Further, sixty percent of 142
      siblings of the RF/RHD patients were "positive" when tested with PGI/MN II. The
      data from these studies suggest that before such MAb can be used for
      identification of RF "susceptibles" in public health programs, variation among
      ethnic populations must be assessed.

PMID- 9579812
TI  - Predictors of death during 5 years after coronary artery bypass grafting.
AB  - AIM: To describe predictors of death during five years of follow-up after
      coronary artery bypass grafting (CABG). METHODS: All patients who underwent CABG
      during a period of three years in Western Sweden were included in the analysis
      and were prospectively followed for five years. Mortality was related to
      preoperative and peroperative factors as well as findings at physical examination
      and medication 4-7 days after the operation. RESULTS: In all 2121 patients
      underwent CABG without simultaneous valve surgery during the study period. The
      overall five-year mortality was 14.6%. The following appeared as independent
      predictors of death during five years but >30 days after CABG: Current smoking
      (relative risk ratio 2.43 [95% Ci 1.64-3.61]) degree of impairment of left
      ventricular function (1.51 [1.23-1.86]), a history of congestive heart failure
      (1.91 [1.35-2.701), age (1.04 [1.02-1.06]) arrhythmia 4-7 days after CABG (1.89
      [1.26-2.83]), intermittent claudication (1.73 [1.19-2.52]), a history of diabetes
      (1.71 [1.16-2.51]), time in respirator (1.43 [1.13-1.81]), a history of
      cerebrovascular disease (1.72 [1.13-2.64]), treatment with digitalis at day 4-7
      (1.48 [1.07-2.05]), enzyme release (1.49 [1.03-2.16]). CONCLUSION: Among patients
      who underwent CABG 11 independent predictors for mortality were found including
      smoking habits at CABG, history of cardiovascular diseases, left ventricular
      dysfunction, age, post operative complications and medication after CABG.

PMID- 9579813
TI  - Interventional study of diltiazem in dilated cardiomyopathy: a report of multiple
      centre clinical trial in China. Chinese Cooperative Group of Diltiazem
      Intervention Trial in Dilated Cardiomyopathy.
AB  - The aim of this study was to determine the interventional effects of diltiazem on
      autoantibody mediated myocardial damage in dilated cardiomyopathy (DCM). 221
      patients with DCM in 16 hospitals were included in the multiple centre clinical
      trial from January 1995 to November 1996, using the diltiazem or placebo based on
      the background therapy for heart failure. Patients were randomly divided into
      groups for a single blind trial, followed by observation for an average of 7.4
      months. After treatment, the heart function of 84% of patients in the diltiazem
      group recovered to grade I or II, but this occurred for 64% of patients in the
      placebo group. Heart-thorax ratio was decreased from 0.59+/-0.07 to 0.56+/-0.07
      and the left ventricular end-diastolic dimension (LVEDd) from 65.40+/-8.60 mm to
      61.12+/-9.86 mm, the left ventricular ejection fraction (EF) was increased from
      35.75+/-10.78% to 42.52%+/-11.41% (P<0.01) in the diltiazem group (n=114). The
      above parameters were not significantly changed in the placebo group (n=107).
      Mortality was 3.5% in the diltiazem group and 11.2% in the placebo group
      (P<0.05). Further analysis also shows that LVEDd were reduced and EF were
      obviously elevated in patients with DCM of LVEDd <70 mm, but the above parameters
      weren't improved in patients of LVEDd >70 mm. The study suggests that diltiazem
      is safe and effective in the treatment of DCM, the action mechanism might be
      intervention in antibody-mediated myocardial damage and protection of myocardium.
      Diltiazem is suitable for the treatment of the early stage in DCM.

PMID- 9579814
TI  - Cardiac involvement in Dengue Haemorrhagic Fever.
AB  - We studied 17 consecutive patients of Dengue Haemorrhagic Fever/Dengue Shock
      Syndrome (DHF/DSS) to assess cardiac function by radionuclide ventriculography,
      echocardiography and electrocardiography (ECG) during the epidemic of Dengue
      virus type-2 (DEN-2) in Delhi, India (1996). Case definitions laid down by the
      WHO were followed. Fourteen patients were seropositive for Dengue infection. In
      radionuclide ventriculography study, the mean left-ventricular ejection fraction
      was 41.69 (5.04% (range 33-49%) and 7 patients had an ejection fraction less than
      40%, global hypokinesia was detected in 12 (70.59%) patients. In
      echocardiography, the mean ejection fraction was 47.06 (3.8%). Eight patients had
      Dengue Shock Syndrome and the mean ejection fraction was 39.63% (4.97% in
      radionuclide ventriculography, out of which 5 patients had an ejection fraction
      below 40%. To find out the nature of myocardial involvement, 99m Tc-pyrophosphate
      imaging was done in 4 patients and it was discontinued further because no
      myocardial necrosis was detected in those patients. Five patients had ST and T
      changes in the electrocardiogram, radionuclide ventriculography and
      echocardiography revealed no abnormalities after 3 weeks of follow up and the
      ejection fraction was more than 50% in all cases. Global hypokinesia also
      improved and ECG changes reverted back to normal within 3 weeks. Acute reversible
      cardiac insult may be noticed in Dengue Haemorrhagic Fever/Dengue Shock Syndrome
      and could be responsible for hypotension/shock seen in some of these patients.
      Further studies are required to establish the pathogenic mechanisms of cardiac
      dysfunction in patients with Dengue Haemorrhagic Fever/Dengue Shock Syndrome.

PMID- 9579816
TI  - Idiopathic ventricular fibrillation: clinical, electrophysiologic characteristics
      and long-term outcomes.
AB  - The long-term prognosis, including risks of arrhythmic recurrence of idiopathic
      ventricular fibrillation (VF), is uncertain; moreover, the role of
      electrophysiologic study in the diagnosis and guiding of antiarrhythmic drugs
      therapy for idiopathic VF remains controversial. The purpose of this study was to
      study the clinical features, electrophysiologic characteristics and long-term
      clinical outcomes of six consecutive patients (five males) who had at least one
      episode of aborted cardiac arrest (5 patients) or syncope (1 patients) with
      documentation of ventricular fibrillation (VF) in the absence of apparent heart
      disease. Idiopathic VF was diagnosed by exclusion. All patients underwent the
      electrophysiologic study including intravenous antiarrhythmic drug testing.
      Recurrences of VF after therapy and the long-term outcomes were assessed. The
      mean age at the first episode was 43+/-19 years (range from 16 to 63 years). All
      patients had sustained VF induced by double (3 patients) or triple (3 patients)
      ventricular extrastimuli at a paced cycle length of 400 or 500 ms from the right
      ventricular apex. Intravenous procainamide and/or mexiletine could suppress the
      reinduction of sustained VF in 4 (67%) of 6 patients. Recurrence of VF
      (documented VF attack, sudden cardiac arrest or syncope) was observed in 3 (100%)
      of 3 patients who received procainamide or mexiletine alone. Four patients
      (including 3 patients who experienced recurrence) received amiodarone alone or in
      combination with mexiletine, and these drugs could effectively prevent recurrence
      of VF. One patient with exercise-induced VF remained asymptomatic without any
      treatment during a follow-up period of 95 months. Another patient received an
      implantable cardioverter-defibrillator without concomitant antiarrhythmic drug
      therapy and had no discharge of electrical shock during 28 months of follow-up.
      During a mean follow-up period of 64+/-40 months (range from 28 to 128 months),
      all the patients were alive except patient No. 2 who died of acute hepatic
      failure. In conclusion, electrophysiologic study is a reliable diagnostic method,
      but it was of limited value in guiding antiarrhythmic drug therapy for preventing
      recurrence of idiopathic VF. Class I drug alone was associated with a high
      recurrence rate (100%) despite predictions that it would be effective by the
      electrophysiologic study. Amiodarone alone or in combination with mexiletine
      effectively prevented the recurrence of VF during the long-term follow-up along
      with a favourable outcome.

PMID- 9579815
TI  - Effects of antiarrhythmic drugs on variability of ventricular rate and exercise
      performance in chronic atrial fibrillation complicated with ventricular
      arrhythmias.
AB  - For conversion of atrial fibrillation to sinus rhythm and management of
      ventricular arrhythmias, antiarrhythmic drugs were frequently used. However, the
      effects of antiarrhythmic drugs on exercise performance and on the variability of
      ventricular rate were not available. This study included 37 patients who had
      chronic atrial fibrillation complicated with symptomatic ventricular arrhythmias.
      The patients were divided into three groups and received sotalol, propafenone,
      and procainamide, respectively. Before and after taking the drugs for 14 days,
      these patients received treadmill exercise test, 24 h Holter electrocardiogram,
      and tilt table test for evaluation of the exercise performance and the
      variability of ventricular rate (including the mean RR intervals, mRR, the
      standard deviation of RR intervals, SDRR, and the root mean square of the
      difference in successive RR intervals, rMSSD). All these antiarrhythmic drugs
      could suppress ventricular arrhythmia but only sotalol could significantly
      increase the exercise duration (374+/-50 to 476+/-55 s, P=0.02), and reduce the
      maximal heart rate (186+/-23 to 136+/-16 beats/min, P=0.01) during exercise test.
      Furthermore, only sotalol increased the mRR (777+/-60 to 885+/-66 ms, P=0.02),
      SDRR (190+/-40 to 216+/-48 ms, P=0.04) and rMSSD (223+/-48 to 253+/-40 ms,
      P=0.03) during 24 h Holter electrocardiogram. With head-up tilt, the mRR, SDRR
      and rMSSD all decreased significantly before drug therapy, and these changes were
      still present only after propafenone therapy. Therefore, comparisons among
      sotalol, propafenone and procainamide showed that sotalol increased the exercise
      performance and the variability of ventricular rate in patients who had chronic
      atrial fibrillation complicated with symptomatic ventricular arrhythmias.

PMID- 9579817
TI  - Increased QT dispersion and other repolarization abnormalities as a possible
      cause of electrical instability in isolated aortic stenosis.
AB  - The aim of our study was to analyze the ventricular repolarization phase in
      patients with isolated aortic stenosis (AS) in order to search for possible
      abnormalities that might contribute to an explanation of the electrical
      instability peculiar to this valve disease. We selected a population of 39
      patients with isolated AS (25 M and 14 F, mean age 60+/-16 yrs). As controls we
      considered a group of 31 age-matched healthy subjects 20 M and 11 F, mean age
      55+/-14 yrs, P=NS. Disease severity was assessed by echocardiography, calculating
      the maximum and mean pressure gradients max and mean PG) and the functional valve
      orifice area. Various electrocardiographic intervals (QT, QT'c, JT, JTc) and
      indices (QT and QTc dispersion were adopted for a detailed non-invasive
      evaluation of the ventricular repolarization. In patients with AS, M-QT (391+/-45
      ms vs 362+/-25 ms, P=0.002), M=QTc (431+/-29 ms vs 412+/-19 ms, P=0.003), M-JT
      (290+/-41 ms vs 265+/-26 ms, P=0.003, M-JTc 331+/-29 ms vs 302+/-19 ms, P<0.001,
      QTD (67+/-34 ms vs 40+/-15 ms, P<0.001), QTcD (77+/-36 ms vs 52+/-23 ms, P<0.001)
      all resulted significantly greater than in controls. QTD and QTcD both resulted
      linearly related either to max PCi (r=0.388, P=0.018 and r=0.357, P=0.03) or to
      mean PG (r=0.513, P=0.004 and r=0.438, P=0.015), while M-JT and M-JTc turned out
      to be directly related only to mean PG (r=0.436, P=0.016 and r=0.483, P=0.007).
      Our findings suggest a prolonged duration of ventricular recovery and a greater
      dispersion of ventricular repolarization in patients with AS and might account
      for the electrical instability proper to this valve dysfunction. Besides, the
      existence of a linear direct relation between the severity of AS and the degree
      of inhomogeneity of left ventricular recovery, together with the correlation
      found among mean PCr and the total duration of the repolarization phase,
      expressed by the intervals JT and JTc, strongly suggest the hypothesis that in AS
      arrhythmogenic substrates development parallels the worsening of the valve
      defect.

PMID- 9579818
TI  - Heart involvement and HIV infection in African patients: determinants of
      survival.
AB  - In Africa, recent studies have reported that HIV may exhibit a cardiac tropism.
      The purpose of this study was to determine if clinical features, sex, age at
      onset, biological or echocardiographic variables have any influence on survival
      of African HIV-infected patients and AIDS progression. One hundred and fifty
      seven consecutive HIV-seropositive patients without cardiac lesions and no other
      AIDS-defining illnesses underwent physical, electrocardiographic and Doppler
      echocardiographic examinations at the Heart of Africa Cardiovascular Centre, Lomo
      Medical, Kinshasa, Congo, between July 1987 and July 1994. Odds ratios were
      calculated to assess the influence of potential risk factors on cardiac lesions,
      opportunistic diseases, and death outcomes. Cardiac lesions had occurred in 87
      patients (55%) during 7-year follow up. The onset of heart involvement was
      associated with a protection against opportunistic comorbidity. In multiple
      regression model, cardiac mass/volume ratio, body temperature, deceleration time,
      body mass index and socio-economic status were each independently associated with
      AIDS outcome. In a multivariate analysis the lowest socioeconomic status and the
      pericardial effusion were the independent predictors of death. The higher CD4
      count and cardiac lesions outcome were connected with slower progression to AIDS.
      Dilated cardiomyopathy was associated with longer survival.

PMID- 9579819
TI  - Prognosis of medically treated patients referred for cardiac transplantation.
AB  - OBJECTIVES: To assess prognosis and factors influencing survival of transplant
      candidates in whom continued medial therapy was recommended in comparison to that
      of immediately listed patients. METHODS: Retrospective analysis of clinical,
      echocardiographic and hemodynamic data as related to survival or listing for
      transplantation of medically treated transplant candidates. PATIENTS: 160
      patients considered 'too well' for cardiac transplantation and 133 patients
      immediately listed for transplantation. RESULTS: Forty-one of the medically
      treated patients deteriorated clinically and were listed after 10.7+/-12.3 months
      after initial evaluation. Mid-term prognosis (2 years) of patients never listed
      was comparable to that of immediately listed patients (74% vs. 70%) but long-term
      prognosis (5 years) was worse (41% vs. 54%, p<0.001). Cardiothoracic ratio and
      pulmonary capillary wedge pressure were independent predictors of survival
      (multivariate analysis) in patients whose NYHA class and physical working
      capacity improved and cardiothoracic ratio decreased significantly after
      adjustment of medical therapy. CONCLUSIONS: Mid-term prognosis of selected
      patients considered 'too well' for transplantation is comparable to patients
      immediately listed. Lower left ventricular filling pressures, smaller hearts on
      chest X-ray on initial evaluation, and improvement of symptoms during follow up
      may identify a subgroup of patients who do well on optimized therapy.

PMID- 9579820
TI  - Noninvasive biomagnetic imaging in coronary artery disease based on individual
      current density maps of the heart.
AB  - OBJECTIVE: In this paper we present an attempt at noninvasive imaging of
      distributed myocardial electrical activity in patients suffering from myocardial
      infarction and in healthy subjects. Although advances have been made, noninvasive
      three-dimensional imaging of cardiac electrophysiological activity is still in
      its infancy and extending our knowledge of cardiac electrophysiological
      properties may be a valuable guide in the treatment of patients with coronary
      artery disease. METHODS: Magnetic field mapping data formed the input for an
      inverse solution that is based on a multiple dipole model. The lead field
      normalized minimum norm least square criterion was applied to predefined
      myocardial source geometry. Current density distributions were calculated for the
      left ventricle during ventricular depolarization. Images from two patients with
      previous myocardial infarction were compared to images from two healthy subjects.
      RESULTS: Low regional and global current density was found in the infarction
      patients. Regions of low current density corresponded to infarcted segments. The
      images of the healthy subjects displayed less marked areas of low current
      density. CONCLUSION: The proposed multiple dipole model may be able to
      distinguish viable from scarred myocardium. A prospective clinical study should
      be undertaken to investigate the spatial resolution and the diagnostic
      performance of this method.

PMID- 9579821
TI  - Idiopathic long QT syndrome with late onset of bradycardia-dependent and short
      coupled variant of torsade de pointes.
AB  - We report an idiopathic variant of the long QT syndrome in a 72 year old woman
      with a history of recurrent syncope over 3 years who presented with repeated
      episodes of cardiac arrest due to bradycardia-dependent torsade de pointes (TdP),
      which continued long after possible triggers were eliminated. During these
      episodes a short coupling interval of the first tacycardia beat was also
      observed. The patient's stormy course was only controlled with pacing. She
      received a permanent dual-chamber pacemaker and prophylactically a beta-blocker
      was added. Over the subsequent 14 months she has remained completely
      asymptomatic.

PMID- 9579822
TI  - A missense mutation in the BRCA2 gene in three siblings with ovarian cancer.
AB  - Inherited susceptibility to ovarian cancer has been associated with germline
      defects at several loci. The major known ovarian cancer susceptibility gene is
      BRCA1 on chromosome 17q, which confers a risk of approximately 60% by the age of
      70 years. Truncating mutations in BRCA2 on chromosome 13q also predispose to
      ovarian cancer, although they confer a lower risk than mutations in BRCA1. We
      have studied the molecular basis of ovarian cancer predisposition in a Finnish
      family with three affected sisters. Analysis of polymorphic markers provided
      evidence against linkage to BRCA1, but the sibship was consistent with linkage to
      BRCA2. Conformation-sensitive gel electrophoresis was used to screen the entire
      coding sequence of BRCA2. A G to A transition at nucleotide 8702 was observed,
      which is predicted to convert glycine 2901 to aspartate in the encoded protein.
      This sequence variant was not detected in 220 cancer-free Finnish control
      individuals, or in several hundred cancer families of many nationalities
      previously screened for BRCA2 mutations. Taken together with the fact that this
      amino acid residue and the surrounding region of BRCA2 is identical in mouse and
      chicken, the data suggest that this alteration is a disease-causing BRCA2
      missense mutation. Previously published data indicate that the risks of breast
      and ovarian cancer conferred by BRCA2-truncating mutations varies with the
      position of the mutation in the gene. The missense mutation reported here
      suggests that the BRCA2 domain including and surrounding glycine 2901 may be more
      important in preventing neoplastic transformation in ovarian epithelium than in
      breast epithelium.

PMID- 9579823
TI  - Putative markers for the detection of breast carcinoma cells in blood.
AB  - The aim of this study was to investigate certain genes for their suitability as
      molecular markers for detection of breast carcinoma cells using the reverse
      transcriptase-polymerase chain reaction (RT-PCR). RNA was prepared from MCF-7
      breast carcinoma cells and peripheral blood leucocytes of healthy female
      volunteers. This RNA was screened for mRNA of MUC1, cytokeratin 19 (CK19) and
      CD44 (exons 8-11) by RT-PCR and the results validated by Southern blots. Variable
      degrees of expression of MUC1 and CD44 (exons 8-11) were detected in normal
      peripheral blood, rendering these genes non-specific for epithelial cells and
      therefore unsuitable for use as markers to detect breast carcinoma cells.
      Although CK19 mRNA was apparently specific, it was deemed unsuitable for use as a
      marker of breast cancer cells in light of its limited sensitivity. Furthermore,
      an attempt at using nested primers to increase sensitivity resulted in CK19 mRNA
      being detected after two amplification rounds in blood from healthy volunteers.

PMID- 9579824
TI  - The promoting effect of tumour necrosis factor alpha in radiation-induced cell
      transformation.
AB  - The ability of tumour necrosis factor alpha (TNF-alpha), a potent endogenous
      inflammatory agent, to promote malignant transformation of Syrian hamster embryo
      cells (SHE) initiated by a 0.5-Gy dose of alpha-particles was investigated.
      Opsonized zymosan particles, which were phagocytosed by a human macrophage-like
      cell line, triggered TNF-alpha production from U937 cells. This cell supernatant
      could significantly increase the transformation frequency (TF) of primary SHE
      cells previously irradiated by a 0.5-Gy dose of alpha-particles. The TF decreased
      significantly if monoclonal antibody against TNF-alpha was added to the
      supernatant. Similarly, recombinant human TNF-alpha (rhTNF-alpha) increased the
      TF of alpha-irradiated primary SHE cells to an even greater extent. Addition of
      TNF-alpha to subcultures of irradiated SHE cells permitted the continuous
      propagation of these primary cells. In contrast, both TNF-alpha-treated control
      and alpha-irradiated cells without subsequent TNF-alpha treatment senesced after
      7-15 passages. Irradiated SHE cells treated continuously with TNF-alpha could be
      subcultured over 40 passages and produced fibrosarcomas upon inoculation into
      nude mice. Our results provide the first evidence that TNF-alpha released by
      activated macrophages may contribute to the process of malignant transformation
      initiated by low-dose alpha-particles.

PMID- 9579825
TI  - The response of Dunning R3327 prostatic adenocarcinoma to IL-2, histamine and
      radiation.
AB  - A syngeneic, androgen-sensitive Dunning R3327 rat prostatic adenocarcinoma was
      transplanted bilaterally in the flanks of male Copenhagen Fisher rats.
      Approximately 3 months after implantation, when the tumours had a median volume
      of 150 mm3, one group of rats was treated with histamine alone (4 mg kg(-1)
      subcutaneously on week days), another group with human recombinant interleukin 2
      (IL-2) alone (425 IU kg(-1) continuous infusion) and a third group with both
      histamine and IL-2 during 6 weeks. Tumours on one flank were irradiated (6 Gy
      once daily for 3 days to a total dose of 18 Gy) beginning 1 week after the onset
      of treatment with histamine and/or IL-2. The contralateral tumour served as the
      intra-animal control. The tumour volumes were determined weekly. The growth
      curves showed that all three drug treatments were effective in delaying growth,
      but when used individually did not cause tumour shrinkage. Radiation was the most
      effective single agent, but when used alone the shrinkage did not occur until 2
      weeks after irradiation. When combined with the drugs, more rapid and extensive
      growth delay and/or shrinkage was seen. The growth curves showed clear
      differences between the different treatments. The combination of the three agents
      was the most effective of all. The most striking difference between radiation
      alone and radiation plus biotherapy was the time at which a tumour response was
      detectable. Thus, active biotherapy alone and especially in a combination with
      histamine and radiotherapy warrants further investigation as a potential
      therapeutic approach to prostate cancer.

PMID- 9579826
TI  - Late G1 accumulation after 2 Gy of gamma-irradiation is related to endogenous Raf
      1 protein expression and intrinsic radiosensitivity in human cells.
AB  - We have previously reported a correlation between high endogenous expression of
      the protein product of the RAF-1 proto-oncogene, intrinsic cellular
      radiosensitivity and rapid exit from a G2/M delay induced by 2 Gy of gamma
      irradiation. Raf1 is a positive serine/threonine kinase signal transduction
      factor that relays signals from the cell membrane to the MAP kinase system
      further downstream and is believed to be involved in an ionizing radiation signal
      transduction pathway modulating the G1/S checkpoint. We therefore extended our
      flow cytometric studies to investigate relationships between radiosensitivity,
      endogenous expression of the Raf1 protein and perturbation of cell cycle
      checkpoints, leading to alterations in the G1, S and G2/M populations after 2 Gy
      of gamma-irradiation. Differences in intrinsic radiosensitivity after modulation
      of the G1/S checkpoint have generally been understood to involve p53 function up
      to the present time. A role for dominant oncogenes in control of G1/S transit in
      radiation-treated cells has not been identified previously. Here, we show in 12
      human in vitro cancer cell lines that late G1 accumulation after 2 Gy of
      radiation is related to both Raf1 expression (r = 0.91, P = 0.0001) and the
      radiosensitivity parameter SF2 (r = -0.71, P = 0.009).

PMID- 9579827
TI  - The antiproliferative activity of all-trans-retinoic acid catabolites and isomers
      is differentially modulated by liarozole-fumarate in MCF-7 human breast cancer
      cells.
AB  - The clinical use of all-trans-retinoic acid (ATRA) in the treatment of cancer is
      significantly hampered by the prompt emergence of resistance, believed to be
      caused by increased ATRA catabolism. Inhibitors of ATRA catabolism may therefore
      prove valuable for cancer therapy. Liarozole-fumarate is an anti-tumour drug that
      inhibits the cytochrome P450-dependent catabolism of ATRA. ATRA, but also its
      naturally occurring catabolites, 4-oxo-ATRA and 5,6-epoxy-ATRA, as well as its
      stereoisomers, 9-cis-RA and 13-cis-RA, show significant antiproliferative
      activity in MCF-7 human breast cancer cells. To further elucidate its mechanism
      of action, we investigated whether liarozole-fumarate was able to enhance the
      antiproliferative activity of ATRA catabolites and isomers. Liarozole-fumarate
      alone up to a concentration of 10(-6) M had no effect on MCF-7 cell
      proliferation. However, in combination with ATRA or the ATRA catabolites,
      liarozole-fumarate (10(-6) M) significantly enhanced their antiproliferative
      activity. On the contrary, liarozole-fumarate (10(-6) M) was not able to
      potentiate the antiproliferative activity of the ATRA stereoisomers, most
      probably because of the absence of cytochrome P450-dependent catabolism.
      Together, these findings show that liarozole-fumarate acts as a versatile
      inhibitor of retinoid catabolism in that it not only blocks the breakdown of
      ATRA, but also inhibits the catabolic pathway of 4-oxo-ATRA and 5,6-epoxy-ATRA,
      thereby enhancing their antiproliferative activity.

PMID- 9579828
TI  - Transfection of COS-1 cells with DT-diaphorase cDNA: role of a base change at
      position 609.
AB  - DT-diaphorase, a homodimeric flavoenzyme, can provide for a defence mechanism
      against carcinogenesis mediated by dietary or environmental quinones as well as
      bioactivate quinone-containing chemotherapeutic drugs. Human cell lines and
      strains have been identified with very low or undetectable enzymatic activity and
      a C to T transition at nucleotide 609 of the DT-diaphorase cDNA. This single base
      change is predicted to result in a proline to serine change in amino acid 187.
      Human cells homozygous for this base transition fail to exhibit Western blot
      reactivity for DT-diaphorase, suggesting that this substitution results in
      protein instability. To directly test whether this base change affects DT
      diaphorase enzymatic activity and/or protein stability in vivo, mammalian
      expression vectors containing DT-diaphorase cDNA with or without the nucleotide
      609 base transition were transiently transfected in COS-1 cells. Co-transfection
      with a human growth hormone expression vector allowed normalization for
      transfection efficiency. COS-1 transfectants expressing the C to T base change
      displayed at least a tenfold reduction in DT-diaphorase activity (P < 0.001) and
      a two- to threefold reduction in protein levels compared with wild-type
      transfectants. These results are the first to detect the presence of DT
      diaphorase protein coded for by the 609 base transition in mammalian cells and
      confirm its predicted reduced enzymatic activity.

PMID- 9579830
TI  - Prognostic significance of methyl-p-hydroxy-phenyllactate-esterase activity in
      laryngeal squamous cell carcinoma.
AB  - We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63
      cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not
      show any correlation with oestrogen, progesterone and epidermal growth factor
      (EGF) receptor levels. No significant relationship was found between MeHPLAase
      activity and age, sex, tumour site, T classification, stage of disease and EGFR
      status, whereas a significant inverse relationship was found between enzymatic
      activity and neck lymph node positivity at presentation. The median value of
      MeHPLAase activity tended to be higher in tumours with low histopathological
      grade than in those with high histopathological grade. During the follow-up
      period (median 50 months, range 2-90 months) locoregional recurrences were
      observed in 31 out of 63 (49%) cases. At the end of the study, 27 out of 63 (43%)
      patients had died of cancer. Cox univariate analysis using MeHPLAase activity as
      a continuous covariate showed that the levels of enzymatic activity were
      inversely associated with the risk of death and relapse. Assuming the mean value
      of enzymatic activity as the cut-off value, we found a statistically significant
      relationship between high MeHPLAase activity and longer relapse-free and overall
      survival. MeHPLAase activity status retained its prognostic significance also in
      the lymph node-negative subgroup of patients. On multivariate analysis, both EGFR
      and MeHPLAase activity proved to be independent factors for predicting a short
      relapse and the overall survival.

PMID- 9579829
TI  - Induction of DT-diaphorase by 1,2-dithiole-3-thiones in human tumour and normal
      cells and effect on anti-tumour activity of bioreductive agents.
AB  - DT-diaphorase is a two-electron-reducing enzyme that is an important activator of
      bioreductive anti-tumour agents, such as mitomycin C (MMC) and EO9, and is
      inducible by many compounds, including 1,2-dithiole-3-thiones (D3Ts). We showed
      previously that D3T selectively increased DT-diaphorase activity in mouse
      lymphoma cells compared with normal mouse marrow cells, and also increased MMC or
      EO9 cytotoxic activity in the lymphoma cells with only minor effects in the
      marrow cells. In this study, we found that D3T significantly increased DT
      diaphorase activity in 28 of 38 human tumour cell lines representing ten tissue
      types with no obvious relationships between the tumour type, or the base level of
      DT-diaphorase activity, and the ability of D3T to increase the enzyme activity.
      Induction of DT-diaphorase activity in human tumour cell lines by 12 D3T
      analogues varied markedly with the D3T structure. D3T also increased DT
      diaphorase activity in normal human bone marrow and kidney cells but the
      increases were small in these cells. In addition, D3T increased the level of
      enzyme activity in normal human lung cells. Pretreatment of human tumour cells
      with D3T analogues significantly increased the cytotoxic activity of MMC or EO9
      in these cells, and the level of enhancement of anti-tumour activity paralleled
      the level of DT-diaphorase induction. In contrast, D3T did not effect the
      toxicity of EO9 in normal kidney cells. These results demonstrate that D3T
      analogues can increase DT-diaphorase activity in a wide variety of human tumour
      cells and that this effect can enhance the anti-tumour activity of the
      bioreductive agents MMC and EO9.

PMID- 9579831
TI  - Down-regulated expression of transforming growth factor beta 1 mRNA in
      endometrial carcinoma.
AB  - Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell
      proliferation in vitro, and recent studies have demonstrated its overexpression
      in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1
      action on cell growth and differentiation have not been fully elucidated. To
      clarify the role of TGF-beta and its receptor in human endometrial proliferation
      and differentiation, TGF-beta1 expression at both the mRNA and protein levels has
      been evaluated by using Northern blotting and immunohistochemistry, in both
      normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma)
      endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is
      dramatically reduced in endometrial carcinomas with respect to non-neoplastic
      tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in
      the epithelial component of endometrial carcinomas compared with non-neoplastic
      tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of
      endometrial cell proliferation and that it may contribute to the carcinogenic
      mechanisms of endometrial carcinoma.

PMID- 9579832
TI  - The detection of K-ras mutations in colorectal cancer using the amplification
      refractory mutation system.
AB  - A total of 301 colorectal carcinoma (CRC) archival samples were analysed using
      the amplification-refractory mutation system (ARMS). Each sample was examined to
      determine the mutation status of codons 12 and 13 of the K-ras oncogene. The
      results from direct DNA sequence analysis carried out on 30 of the samples
      differed from the ARMS result in almost 50% of the cases as a result of the
      relative excess of wild-type to mutated DNA sequences. To assess the validity of
      the ARMS data, the polymerase chain reaction (PCR) was used to generate an
      amplicon from K-ras exon 1 from 23 of the samples. The PCR amplicons were cloned
      and sequenced, and the DNA sequence analysis of the cloned material was in
      agreement with the ARMS results in all but one case. This case represented a
      tumour that exhibited a five-nucleotide reversed inversion. The cloned sequence
      data confirm the sensitivity and specificity of the individual ARMS reactions and
      that it is possible in certain cases to detect additional, more complex, sequence
      variations.

PMID- 9579834
TI  - Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine
      (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and
      interleukin (IL-2) in patients with metastatic melanoma.
AB  - The purpose of this study was to evaluate in a randomized phase II trial the
      efficacy and toxicity of combination biochemotherapy compared with chemotherapy
      alone in patients with metastatic melanoma. Sixty-five patients with metastatic
      melanoma (ECOG performance status 0 or 1) were randomized to receive intravenous
      BCNU 100 mg m(-2) (day 1, alternate courses), cisplatin 25 mg m(-2) (days 1-3),
      DTIC 220 mg m(-2) (days 1-3) and oral tamoxifen 40 mg (BCDT regimen) with (n =
      35) or without (n = 30) subcutaneous interleukin 2 (IL-2) 18 x 10(6) iu t.d.s.
      (day - 2), 9 x 10(6) iu b.d. (day - 1 and 0) and interferon 2 alpha (IFN-alpha) 9
      MU (days 1-3). Evidence for immune activation was determined by flow cytometric
      analysis of peripheral blood lymphocytes. Treatment was repeated every 4 weeks up
      to six courses depending on response. The overall response rate of BCDT with IL
      2/IFN-alpha was 23% [95% confidence interval (CI) 10-40%] with one complete
      response (CR) and seven partial responses (PR), and for BCDT alone 27% (95% CI 12
      46%) with eight PRs; the median durations of response were 2.8 months and 2.5
      months respectively. Sites of response were similar in both groups. There was no
      difference between the two groups in progression-free survival or overall
      survival (median survival 5 months for BCDT with IL-2/IFNalpha and 5.5 months for
      BCDT alone). Although 3 days of subcutaneous IL-2 resulted in significant
      lymphopenia, evidence of immune activation was indicated by a significant rise in
      the percentage of CD56- (NK cells) and CD3/HLA-DR-positive (activated T cells)
      subsets, without any change in the percentage of CD4 or CD4 T-cell subsets.
      Toxicity assessment revealed a significantly higher incidence of severe
      thrombocytopenia in patients treated with combination chemotherapy than with
      chemotherapy alone (37% vs 13%, P = 0.03) and a higher incidence of grade 3/4 flu
      like symptoms (20% vs 10%) and fatigue (26% vs 13%). The addition of subcutaneous
      IL-2 and IFNalpha to BCDT chemotherapy in a randomized phase II trial resulted in
      immune activation but did not improve response rates in patients with metastatic
      melanoma, and indeed may increase some treatment-related toxicity.

PMID- 9579833
TI  - Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms
      with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell
      carcinoma of the skin.
AB  - Desmosomes are intercellular junctions that have been shown to be down-regulated
      in certain types of carcinoma and that may play a role in suppression of invasion
      and metastasis. This paper describes an immunohistochemical study of three types
      of epidermal neoplasms with monoclonal antibody to desmoglein in order to
      determine how desmosomal staining correlates with the clinical, biological and
      histopathological features of these neoplasms. Actinic keratosis (AK) is the most
      common keratinocytic premalignant neoplasm that was reported to have a 10-20%
      rate of malignant transformation into squamous cell carcinoma (SCC).
      Keratoacanthoma (KA) is a benign neoplasm that involutes spontaneously after a
      few months of rapid growth. SCC is a malignant tumour capable of metastasis.
      Electron microscope studies of KA and SCC showed significantly reduced staining
      for desmosomes in SCC but not in KA. We have examined staining for desmoglein
      using the monoclonal antibody 33-3D, a mouse IgM monoclonal antibody, that
      recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen
      sections. Immunohistochemical staining of normal skin with this antibody revealed
      strong pericellular localization of the antigen, outlining the cell membranes of
      the keratinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained
      immunohistochemically with 33-3D monoclonal antibody. All examined KAs showed
      extensive pericellular staining for Dsg. By contrast, juxtanuclear staining for
      Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The
      five remaining SCCs showed focal pericellular staining for the Dsg marker. The
      most common finding in AK was focal pericellular staining for Dsg, with complete
      absence of staining in dysplastic areas (25 cases). In five cases negative
      pericellular staining in dysplastic areas was associated with juxtanuclear
      accumulation of the Dsg marker. A strong negative correlation between Dsg
      staining and degree of dysplasia was obtained. The Dsg pattern in KA is similar
      to normal epidermis and shows a clear difference between KA and SCC. AK has a
      limited loss of Dsg expression in a SCC-like pattern that is congruent with its
      premalignant nature. As the stain works on frozen tissue, it may be helpful for
      rapid differentiation in selected cases in cutaneous oncology and Mohs
      micrographic surgery. This antibody may also have great potential for the
      detection of the effects of chemopreventive agents in skin cancer.

PMID- 9579835
TI  - Adjuvant therapy for melanoma: How should we respond to high-dose interferon?

PMID- 9579836
TI  - Recombinant human granulocyte colony-stimulating factor (filgrastim) following
      high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade
      non-Hodgkin's lymphoma: clinical benefits at no extra cost.
AB  - In order to evaluate the potential clinical and economic benefits of granulocyte
      colony-stimulating factor (G-CSF, filgrastim) following peripheral blood
      progenitor cells (PBPC) rescue after high-dose chemotherapy (HDCT), 23
      consecutive patients aged less than 60 years with poor-prognosis, high-grade non
      Hodgkin's lymphoma (NHL) were entered into a prospective randomized trial between
      May 1993 and September 1995. Patients were randomized to receive either PBPC
      alone (n = 12) or PBPC+G-CSF (n = 11) after HDCT with busulphan and
      cyclophosphamide. G-CSF (300 microg day[-1]) was given from day +5 until recovery
      of granulocyte count to greater than 1.0 x 10(9) l(-1) for 2 consecutive days.
      The mean time to achieve a granulocyte count > 0.5 x 10(9) l(-1) was
      significantly shorter in the G-CSF arm (9.7 vs 13.2 days; P<0.0001) as was the
      median duration of hospital stay (12 vs 15 days; P = 0.001). In addition the
      recovery periods (range 9-12 vs 11-17 days to achieve a count of 1.0 x 10(9) l[
      1]) and hospital stays (range 11-14 vs 13-22 days) were significantly less
      variable in patients receiving G-CSF in whom the values clustered around the
      median. There were no statistically significant differences between the study
      arms in terms of days of fever, documented episodes of bacteraemia, antimicrobial
      drug usage and platelet/red cell transfusion requirements. Taking into account
      the costs of total occupied-bed days, drugs, growth factor usage and
      haematological support, the mean expenditure per inpatient stay was pound
      sterling 6500 (range pound sterling 5465-pound sterling 8101) in the G-CSF group
      compared with pound sterling 8316 (range pound sterling 5953-pound sterling
      15,801) in the group not receiving G-CSF, with an observed mean saving of 1816
      per patient (or 22% of the total cost) in the G-CSF group. This study suggests
      that after HDCT and PBPC rescue, the use of G-CSF leads to more rapid
      haematological recovery periods and is associated with a more predictable and
      shorter hospital stay. Furthermore, and despite the additional costs for G-CSF,
      these clinical benefits are not translated into increased health care
      expenditure.

PMID- 9579837
TI  - Late effects of treatment for early-stage Hodgkin's disease.
AB  - A comprehensive survey of late effects (physical, social and reproductive)
      following treatment at a single institution for early stage Hodgkin's disease
      (HD) was performed. A total of 611 patients with stage I and II HD treated
      between 1973 and 1984 were reviewed; 460 were alive and were mailed a self
      reported questionnaire. A total of 363 (79%) replies were received. Twenty
      patients died of second malignancy, 14 of heart disease and nine from respiratory
      disease. There were 37 cases of second malignancy [relative risk (RR) 2.2,
      absolute excess risk (AR) 35.8]. The 15-year incidence of heart disease was 11%
      and there were nine myocardial infarction deaths (RR 1.55, AR 5.4). Twenty-eight
      (8%) respondents stated that their career had been greatly interfered with, 53
      (14.5%) perceived financial loss. Sexual activity was disrupted in 25.8%. In
      total, 56 men had fathered 112 pregnancies. Of 171 women, 40.3% became pregnant,
      resulting in 92 live births. A total of 43 men and 16 women had sought medical
      advice with regard to infertility.

PMID- 9579839
TI  - Are cytokine responses in renal cell cancer the product of placebo effect of
      treatment or true biotherapy? What trials are needed now?

PMID- 9579838
TI  - Survival in renal cell carcinoma-a randomized evaluation of tamoxifen vs
      interleukin 2, alpha-interferon (leucocyte) and tamoxifen.
AB  - Metastatic renal cell carcinoma (RCC) has a poor prognosis. Conventional
      treatment strategies, including chemotherapy and hormonal therapy, have limited
      value. Although encouraging results have been achieved in terms of objective
      response using immunological manipulations, no conclusive studies yet exist with
      a controlled comparative evaluation of survival. Therefore, the present study was
      undertaken, which compared one of the present (and presumed best) treatments,
      interleukin 2/interferon-alpha (IL-2/IFN-alpha) and tamoxifen, with a control arm
      of tamoxifen only. Tamoxifen has been shown to potentiate in vivo anti-tumour
      activity of IL-2, and because of its non-toxic behaviour it was included in both
      groups. The study was open, randomized and included seven institutions in Sweden.
      The patients were stratified according to the different centres involved. An
      interim analysis was planned when a minimum of 100 patients were evaluable. The
      128 patients finally included had a histologically documented metastatic RCC,
      with a life expectancy of more than 3 months, a performance status WHO 0-2 and no
      prior chemo- or immunotherapy. Informed consent was obtained from each patient.
      The patients randomized to the control arm (n = 63) received only tamoxifen 40 mg
      p.o. daily for at least 1 year or until progression. The patients (n = 65)
      randomized to biotherapy received subcutaneous recombinant IL-2, leucocyte IFN
      alpha in a treatment cycle of 42 days, as well as tamoxifen p.o. In the absence
      of undue toxicity or disease progression, these patients received one additional
      treatment cycle of 42 days followed by maintenance treatment, consisting of 5
      days therapy every 4 weeks, for 1 year, or until proven progression. Only two
      patients in the tamoxifen-only group received immunotherapy when the disease
      progressed, but without any beneficial effect. All patients received appropriate
      local treatment when indicated. The interim analysis demonstrated no survival
      advantage for either group, and therefore further inclusion of patients was
      stopped. The median follow-up was 11 months (range 0.4-48 months). The final
      survival analysis showed no significant differences between the two treatment
      arms in so far as comparison from the day of diagnosis of primary disease, from
      the day of first evidence of metastatic spread, or from the onset of treatment.
      This was valid both when the evaluation was performed with regard to intention to
      treat and when the analysis was directed only to patients that managed at least
      one treatment cycle (42 days) of IL-2/IFN-alpha. The adverse effects were more
      pronounced in the IL-2/IFN-alpha group. Although the number of patients is
      limited, the results raise doubt concerning immunotherapy with IL-2 and IFN-alpha
      as a routine treatment in the management of advanced RCC. The difference in cost
      of drugs and health care (drug costs per patient: IL-2/IFN-alpha $27000 vs
      tamoxifen $360) as well as adverse effects caused by IL-2/IFN-alpha are also
      factors of importance. The study emphasizes the need for more effort to find the
      'optimal schedule' of immunotherapy, as well as the need for randomized
      controlled studies before approval of a new treatment in the routine setting.

PMID- 9579840
TI  - Improving survival in recurrent medulloblastoma: earlier detection, better
      treatment or still an impasse?
AB  - Early detection of relapse has been advocated to improve survival in children
      with recurrent medulloblastoma. However, the prognostic factors and the longer
      term outcome of these patients remains unclear. Pattern of recurrences were
      analysed in three consecutive protocols of the Societe Francaise d'Oncologie
      Pediatrique (1985-91). A uniform surveillance programme including repeated lumbar
      puncture combined with computerized tomography (CT) or magnetic resonance imaging
      (MRI) scan was applied for all registered patients. Forty-six out of 116 patients
      had progressive or recurrent disease. The median time from diagnosis to
      recurrence was 10.5 months and 76% relapses occurred during the first 2 years.
      Seventeen patients had asymptomatic relapses that were detected by the
      surveillance protocol. Forty-one patients were treated at time of progression.
      Twenty-three responded to salvage therapy and 11 achieved a second complete
      remission. The median survival time after progression was 5 months (<1-41
      months), and only two patients remained alive at time of follow-up. Length of
      survival is primarily related to some specific patterns of relapse (time from
      diagnosis to recurrence, circumstances of relapse, extent of relapse) and to the
      response to salvage therapy. No evidence of long-term benefit appeared from any
      form of treatment.

PMID- 9579841
TI  - Cytokeratin 20 mRNA in peripheral venous blood of colorectal carcinoma patients.
AB  - A highly sensitive system was previously developed by us to detect the presence
      of colorectal carcinoma cells in blood in the form of cytokeratin 20 (CK20) mRNA.
      In the present study, we used an improved version of this system to analyse the
      peripheral blood of 28 patients with colorectal carcinoma, five patients with non
      cancerous intestinal diseases and six normal controls for the presence or absence
      of CK20 mRNA and to investigate the relationship between the mRNA results and
      prognosis. All eight patients with recurrence were positive for CK20 mRNA, as
      were four patients in the Dukes' C stage with either distant metastasis or
      dissemination. Five of the nine patients in the Dukes' C stage with neither
      distant metastasis nor dissemination were positive, and three of these developed
      recurrence within 11 months after the analysis. Only one of the seven patients in
      the Dukes' A or B stage was positive, and none showed recurrence during the 1-19
      months of observation. None of the five patients without carcinomas or of the six
      normal controls was positive. Although the follow-up period is limited and the
      recurrences were all local at present, these results suggest that the presence of
      CK20 mRNA in circulation may be a useful indicator for the screening of advanced
      colorectal carcinoma patients with a high risk of recurrence.

PMID- 9579842
TI  - Apparent lack of prognostic value of MIB-1 index in anal carcinomas treated by
      radiotherapy.
AB  - This study was conducted to investigate the influence of Mib-1 index on outcome
      in 55 patients with T1-4 anal carcinomas treated radically by radiotherapy (RT)
      alone (24) or by concomitant chemo-radiotherapy (31). Median follow-up for
      surviving patients was 94 months (range 17-179 months). Tissue materials were
      obtained from pretreatment biopsies. A modified immunoperoxidase technique
      consisting of microwave heating of routinely processed material was employed
      using the Mib-1 antibody (Immunotech, 1:50). The median Mib-1 index for all
      patients was 53% (range 18-96%). Subgroups of patients with high vs low Mib-1
      indices (separated by the median value) had statistically similar outcomes
      regarding 5-year overall survival (64% vs 65% P = 0.7), locoregional control (77%
      vs 69%, P = 0.5) and disease-free survival (73% vs 66%, P = 0.5). Moreover, no
      significant association was found between mean Mib-1 indices and various
      clinicopathological parameters studied (age, sex, circumferential tumour extent,
      T-stage, N-stage and histological type). In conclusion, Mib-1 index failed to
      predict the outcome of patients with anal carcinomas treated conservatively by
      radiotherapy with or without chemotherapy. It is noteworthy that the median Mib-1
      index observed in anal carcinomas in this study was among the highest yet
      reported for cancers of epithelial origin.

PMID- 9579843
TI  - Chromosomal imbalances in primary and metastatic pancreatic carcinoma as detected
      by interphase cytogenetics: basic findings and clinical aspects.
AB  - To date, cytogenetic studies on pancreatic carcinoma are rare, and little is
      known about the frequency of cytogenetic aberrations in primary carcinomas
      compared with metastatic tumour cells. We therefore evaluated the frequency of
      chromosomal aberrations in 12 primary pancreatic carcinomas and in effusion
      specimens from 25 patients with pancreatic cancer by using interphase
      fluorescence in situ hybridization (FISH) and a panel of four centromeric probes.
      Hyperdiploidy and chromosomal imbalances, predominantly affecting chromosome 8,
      were a constant finding in metastatic effusion cells, whereas concordant gain of
      chromosomes or relative loss of chromosome 18 characterized primary pancreatic
      carcinomas. The potential role of oncogenes located on chromosome 8 for
      pancreatic cancer progression was further investigated by double-hybridization
      studies of aneuploid effusion cells with a probe to 8q24 (MYC) and a centromeric
      probe to chromosome 8, which demonstrated amplification of the MYC oncogene in
      two of ten cases (20%). Finally, a potential application of basic findings in the
      clinical setting was tested by searching for micrometastatic cells in effusions
      from pancreatic cancer patients primarily negative by FISH. Two-colour FISH in
      combination with extensive screening (>10,000 nuclei) seems to be a useful tool
      to unequivocally identify micrometastatic cells by demonstrating hyperdiploidy
      and intranuclear chromosomal heterogeneity.

PMID- 9579844
TI  - Who and what influences delayed presentation in breast cancer?
AB  - This study aimed to examine the extent and determinants of patient and general
      practitioner delay in the presentation of breast cancer. One hundred and eighty
      five cancer patients attending a breast unit were interviewed 2 months after
      diagnosis. The main outcome measures were patient delay in presentation to the
      general practitioner and non-referral by the general practitioner to hospital
      after the patient's first visit. Nineteen per cent of patients delayed > or = 12
      weeks. Patient delay was related to clinical tumour size > or = 4 cm (P = 0.0002)
      and with a higher incidence of locally advanced and metastatic disease (P =
      0.01). A number of factors predicted patient delay: initial breast symptom(s)
      that did not include a lump (OR 4.5, P = 0.003), not disclosing discovery of the
      breast symptom immediately to someone else (OR 6.0, P < 0.001), seeking help only
      after being prompted by others (OR 4.4, P = 0.007) and presenting to the general
      practitioner with a non-breast problem (OR 3.5, P = 0.03). Eighty-three per cent
      of patients were referred to hospital directly after their first general
      practitioner visit. Presenting to the GP with a breast symptom that did not
      include a lump independently predicted general practitioner delay (OR 3.6, P =
      0.002). In view of the increasing evidence that delay adversely affects survival,
      a large multicentre study is now warranted to confirm these findings that may
      have implications for public and medical education.

PMID- 9579845
TI  - Combined intravenous and intraperitoneal chemotherapy with fluorouracil +
      leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon
      carcinoma.
AB  - Adjuvant chemotherapy with fluorouracil (FU) and levamisole or FU/leucovorin (LV)
      has been established as effective adjuvant treatment for patients with stage III
      colon cancer. Among several other promising treatment strategies in resected
      colon cancer, intraperitoneal anti-cancer drug administration with its appealing
      rationale of counteracting microscopic residual disease on peritoneal surfaces
      and occult metachronous liver metastases by achieving high intraportal drug
      concentrations has not yet undergone sufficient clinical evaluation. To determine
      whether a combination of this locoregional therapeutic concept with systemic
      intravenous administration of FU/LV would yield better results than conventional
      adjuvant chemoimmunotherapy with FU/levamisole, the present randomized study was
      initiated. A total of 241 patients with resected stage III or high-risk stage II
      (T4N0M0) colon cancer were randomly assigned to 'standard therapy' with FU and
      levamisole, given for a duration of 6 months, or to an investigational arm,
      consisting of LV 200 mg m(-2) plus FU 350 mg m(-2), both administered
      intravenously (days 1-4) and intraperitoneally (days 1 and 3) every 4 weeks for a
      total of six courses. In patients with stage II disease, no significant
      difference was noted between the two arms after a median follow-up time of 4
      years (range 2.5-6 years). Among 196 eligible patients with stage III disease,
      however, a comparative analysis of the two treatment groups suggested both an
      improvement in disease-free survival (P = 0.0014) and a survival advantage (P =
      0.0005), with an estimated 43% reduction in mortality rate (95% confidence
      interval 26-70%) in favour of the investigational arm. In agreement with its
      theoretical rationale, combined intraperitoneal and intravenous FU/LV was
      particularly effective in reducing locoregional tumour recurrences with or
      without liver or other organ site involvement (9 vs 25 patients in the
      FU/levamisole arm; P = 0.005). Treatment-associated side-effects were infrequent
      and generally mild in both arms, although a lower rate of severe (WHO grade 3)
      adverse reactions was noted in patients receiving locoregional plus intravenous
      chemotherapy (3% vs 12%; P = 0.01). The results of this trial suggest that
      combined intraperitoneal plus systemic intravenous chemotherapy with FU/LV is a
      promising adjuvant treatment strategy in patients with surgically resected stage
      III colon carcinoma.

PMID- 9579847
TI  - Predicting chemotherapeutic response to small-cell lung cancer of platinum
      compounds by thallium-201 single-photon emission computerized tomography.
AB  - Thallium-201 single-photon emission computerized tomography (SPECT) was used to
      clarify the relationship between 201Tl uptake and the response in chemotherapy to
      platinum compounds in 21 patients with small-cell lung cancer. 201Tl-SPECT scans
      were obtained twice: at 15 min (early scan) and 120 min (delayed scan) after an
      intravenous injection of 111 MBq (3 mCi) of thallium-201 chloride. We obtained
      the uptake ratio from each scan and calculated the retention index:uptake ratio =
      region of interest uptake/contralateral normal lung uptake; retention index =
      (delayed ratio - early ratio)/early ratio. After 201Tl scintigraphy, 12 patients
      received chemotherapy consisting of platinum compounds and nine were treated with
      chemoradiation. Among patients receiving only chemotherapy, the retention index
      correlated with the responses to chemotherapy. In an in vitro study, ouabain, an
      inhibitor of the Na,K-ATPase pump, reduced sensitivity to cisplatin and inhibited
      intracellular thallium uptake in the small-cell lung cancer cell line. These
      studies suggest that 201Tl-SPECT is a useful indicator of response to
      chemotherapy with platinum compounds in small-cell lung cancer, and that Na,K
      ATPase is commonly involved in transporting both thallium and platinum compounds
      into cancer cells.

PMID- 9579846
TI  - Analysis of risk factors for cisplatin-induced ototoxicity in patients with
      testicular cancer.
AB  - This study evaluates the degree and relevance of persisting ototoxicity after
      cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis
      on identification of potential factors for an increased risk of this late sequel.
      Hearing thresholds of 86 patients with a median age of 31 years (range 21-53
      years) and a median follow-up time of 58 months (range 15-159 months) were
      assessed by conventional pure-tone audiometry. Interviews were conducted
      evaluating the patients' history with special regard to audiological risk
      factors, as well as circumstances of ototoxic symptoms. Details concerning
      treatment and patient variables were extracted retrospectively from the patients'
      charts. An additional screening programme assessed current body functions, blood
      parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of
      patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced
      completely reversible ototoxic symptoms for a duration of 1-18 months after
      treatment. Symptoms were bilateral in 81% of patients. Hearing thresholds were
      compatible with cisplatin-induced hearing loss in 42% of audiograms performed.
      Subjective (history) and objective (audiogram) findings were not always
      consistent. The following statistically significant risk factors for ototoxicity
      were established: high cumulative dose of cisplatin (P < 0.0001); history of
      noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001)
      seemed to result in reversible ototoxic symptoms. No other independent risk
      factors were identified. In conclusion, persisting ototoxicity represents a
      clinical sequel for approximately 20% of testicular cancer patients treated at
      standard dose but may affect more than 50% of patients receiving cumulative doses
      of cisplatin > 400 mg m(-2). Previous noise exposure may also result in a
      threefold increased risk for cisplatin ototoxicity. Future studies should use
      these risk factors as important stratification criteria for trials aiming at the
      evaluation and prevention of cisplatin-induced ototoxicity.

PMID- 9579849
TI  - Assessing patients' needs and preferences in the management of advanced
      colorectal cancer.
AB  - Clinical decision-making in advanced cancer is a highly complex process. Many
      factors are thought to influence this process arguably the most important of
      these is the patient's own preference. Studies show that most patients want to be
      fully informed as to their diagnosis and involved in clinical decision-making.
      However, the attitudes of healthcare workers often preclude patient involvement.
      Studies have also shown that acceptability of chemotherapy for minimal
      therapeutic gain differs markedly between patients depending on factors such as
      age, gender and family status. It is clearly impossible to make decisions about
      what is best for patients without involving them in the decision-making process.
      Indeed, it could be argued that active patient participation actually simplifies
      this process.

PMID- 9579848
TI  - Multidisciplinary case teams: an approach to the future management of advanced
      colorectal cancer.
AB  - The effective management of advanced colorectal cancer has traditionally been
      viewed in terms of treatment outcome measures such as efficacy (survival,
      objective response and palliation) and safety. Although these outcomes are of
      paramount importance and are essential for the evaluation of the effectiveness
      and tolerability of treatment, they do not take account of the global effect of
      therapy on patients, society and healthcare systems. Furthermore, they may not
      reveal important differences between treatments of equivalent anti-tumour
      efficacy that might influence the overall effectiveness in terms of acceptability
      of therapy. To achieve this, a broader, patient-centred evaluation of advanced
      cancer treatment is required that acknowledges the views, experience and
      perspectives of all involved in the treatment process. To this end, the
      International Working Group in Colorectal Cancer, a multidisciplinary group that
      encompasses expertise from a range of relevant fields and disciplines, has
      advocated a multidisciplinary approach to the treatment of advanced colorectal
      cancer that is likely to deliver the best possible overall care.

PMID- 9579850
TI  - Measuring quality of life: impact of chemotherapy for advanced colorectal cancer.
      Experience from two recent large phase III trials.
AB  - When assessing the value of a particular treatment, it is important to consider
      the impact it may have on the quality of life of those being treated. This is
      particularly so for cancer patients, whose life expectancy may be short. Patients
      with advanced colorectal cancer who participated in two international comparative
      studies of raltitrexed ('Tomudex') vs standard 5-fluorouracil (5-FU) plus
      leucovorin (LV) completed previously validated quality-of-life questionnaires
      (EORTC questionnaire, EuroQol and Rotterdam Symptom Check List) at various times
      during the studies. Early statistically significant advantages of raltitrexed vs
      5-FU plus LV on quality of life were observed at week 2 in five of eight of the
      EuroQol and three of four of the Rotterdam Symptom Check List dimensions. Such
      advantages were not observed using the EORTC questionnaire, which was not
      completed until week 12. The necessary dose delays and different dose schedules
      made it difficult in these studies to compare the impact on quality of life of
      the two treatments. It may be that performance status, effect on disease-related
      symptoms and the incidence of toxicity are the most important indications of a
      patient's quality of life.

PMID- 9579851
TI  - Mature results from three large controlled studies with raltitrexed ('Tomudex').
AB  - Since the publication of the results of phase I dose-finding studies, an
      extensive phase II and III clinical study programme has been undertaken to study
      the clinical efficacy and tolerability of the quinazoline folate analogue
      raltitrexed ('Tomudex'), a novel direct and specific inhibitor of thymidylate
      synthase. Two international phase III trials, studies 3 and 12, have compared
      raltitrexed 3 mg m(-2) with 5-fluorouracil (5-FU) plus low-dose leucovorin (LV)
      (Mayo regimen) or high-dose LV (Machover regimen) respectively. A North American
      study (study 10) was originally set up to compare two raltitrexed dosage arms
      (3.0 and 4.0 mg m[-2]) with 5-FU and low-dose LV, but the 4.0 mg m(-2) arm was
      discontinued prematurely because of excessive toxicity. Minimum follow-up times
      for studies 3, 10 and 12 were 15.5, 12 and 9 months, respectively (for data other
      than survival), with corresponding survival follow-up times of 26, 12 and 17
      months. Objective response rates were similar for raltitrexed and 5-FU + LV, and
      palliative improvements were seen to a similar extent with both treatments in all
      phase III studies. Survival was statistically similar for raltitrexed and 5-FU +
      LV in both studies 3 and 12. Raltitrexed was, however, associated with inferior
      survival to 5-FU + low-dose LV in study 10, but there appears to be evidence that
      this was linked to an unconscious effect on investigator behaviour of early
      toxicity problems in this trial, in that patients appeared to be withdrawn from
      raltitrexed treatment without progression or protocolled toxicity. Moreover, it
      appeared that 5-FU + LV patients were continued on treatment after disease
      progression. 5-FU-based therapy was associated with a higher incidence of
      mucositis than raltitrexed in all studies, with the attainment of statistical
      significance in studies 3 and 12. Elevations in hepatic transaminase levels were
      seen with raltitrexed, but these are thought to be of no clinical significance.
      Overall, much greater levels of toxicity were seen with 5-FU + LV than with
      raltitrexed in early treatment cycles. In addition, retrospective UK audit data
      have shown the monthly cost of raltitrexed therapy to be similar to that of Mayo
      and continuous infusion 5-FU regimens, and appreciably lower than that of the de
      Gramont regimen of 5-FU (bolus + 22-h infusion) + high-dose LV. Thus, raltitrexed
      is an effective alternative to 5-FU-based therapy in patients with advanced
      colorectal cancer, with an acceptable and, unlike 5-FU, predictable toxicity
      profile. In particular, patients receiving raltitrexed may benefit from the
      minimization or avoidance of mucositis, and both patients and healthcare
      providers may find the convenient administration schedule of the drug
      advantageous.

PMID- 9579852
TI  - The establishment of a large collaborative trial programme in the adjuvant
      treatment of colon cancer.
AB  - After many years, during which the assumption prevailed that adjuvant
      chemotherapy was of no benefit in patients with resectable adenocarcinoma of the
      colon, findings of several large USA studies published from the late 1980s have
      caused a marked shift in surgical and medical opinion. Although results in
      patients with Dukes' B disease have not shown any clear benefit, the efficacy of
      adjuvant chemotherapy has nevertheless been shown in those with Dukes' C colon
      cancer. As a result, the Mayo regimen of 5-fluorouracil (5-FU) with low-dose
      leucovorin (LV) has become accepted as standard adjuvant therapy in these
      patients. However, the disadvantages associated with standard 5-FU-based
      treatment, particularly those relating to its toxicity and inconvenience of
      administration, have generated interest in other regimens and agents. The novel
      direct and specific thymidylate synthase inhibitor raltitrexed ('Tomudex') has
      been associated with similar objective response rates to standard therapy with 5
      FU plus LV in patients with advanced colorectal cancer. In addition, raltitrexed
      has an attractive tolerability profile compared with that of 5-FU plus LV
      (specifically with respect to lower incidences of mucositis and leucopenia), and
      the simple 3-weekly administration schedule may be considered more convenient by
      many patients and may reduce healthcare resource consumption. To investigate
      alternatives to the Mayo regimen in the adjuvant treatment of Dukes' C
      adenocarcinoma of the colon, two large European trials have been set up: (1)
      PETACC-1 (first Pan-European Trial for Adjuvant Treatment of Colon Cancer), to
      compare raltitrexed with the Mayo regimen of 5-FU and low-dose LV; (2) PETACC-2
      (second Pan-European Trial), to compare the Mayo regimen with three regimens in
      which 5-FU is given by prolonged infusion. These trials will provide valuable
      international data to add to those from the USA and will assess the place of
      raltitrexed in the adjuvant treatment of Dukes' C colon cancer. They will also
      compare directly for the first time infusional and bolus 5-FU regimens in the
      adjuvant setting.

PMID- 9579853
TI  - New developments in cancer treatment with the novel thymidylate synthase
      inhibitor raltitrexed ('Tomudex').
AB  - Following the demonstration of efficacy, tolerability and quality-of-life
      benefits of raltitrexed ('Tomudex'), principally in advanced colorectal but also
      in other cancers, an extensive evaluation of combination therapy with other
      agents in patients with colorectal and other tumour types is being undertaken.
      This work has been prompted by preclinical observations of enhanced activity of
      raltitrexed when coadministered with other cytotoxic agents or radiotherapy and
      by preliminary results showing the activity of raltitrexed in patients with
      cancers other than colorectal. Raltitrexed is currently being investigated as
      monotherapy in phase I and II cancer studies, including head and neck cancer,
      hormone-resistant prostate cancer, paediatric and adult leukaemias and solid
      tumours, and soft tissue sarcoma. In addition, phase I clinical trials are
      evaluating the drug in combination with taxanes (paclitaxel) in solid tumours,
      anthracyclines (doxorubicin) in gastric carcinoma, topoisomerase I inhibitors
      (CPT-11) and 5-fluorouracil (both infusion and bolus regimens) in advanced
      colorectal cancer, platinum compounds (oxaliplatin and cisplatin) in a variety of
      tumours and radiotherapy in rectal cancer. Preliminary reports indicate good
      tolerability and acceptability of the combinations being investigated, with no
      dose-limiting toxicity being reported to date, and some early indications of
      efficacy.

PMID- 9579854
TI  - From rhyme to reason.

PMID- 9579855
TI  - Drug delivery and targeting.
AB  - When a pharmaceutical agent is encapsulated within, or attached to, a polymer or
      lipid, drug safety and efficacy can be greatly improved and new therapies are
      possible. This has provided the impetus for active study of the design of
      degradable materials, intelligent delivery systems and approaches for delivery
      through different portals in the body.

PMID- 9579856
TI  - New directions for organ transplantation.
AB  - Organ transplantation is in many cases the preferred treatment for the chronic
      failure of the major organs. There has been considerable success in preventing
      the rejection of transplanted organs, and further improvements in the outcome of
      transplantation are in prospect. However, the main limitation on the fullest
      possible use of organ transplantation is the shortage of donated human organs.
      One solution to this problem would be xenotransplantation, the use of animals
      instead of humans as the source of organs and tissues for transplant. The
      immunological barriers to this procedure are now well defined and this review
      describes the various strategies that are being developed to try to overcome
      them.

PMID- 9579857
TI  - Cell therapy.
AB  - Cell therapy has emerged as a strategy for the treatment of many human diseases.
      Because no single cell or universal donor is likely to be useful for all
      diseases, it is the source and the desired function of the cell that will dictate
      which cell type is most useful for each disease. Concerns related to
      immunological compatibility, ability to multiply cells in vitro before
      transplantation and general issues of quality control and safety are now being
      addressed by the convergence of disciplines interested in the potential for cell
      therapy.

PMID- 9579858
TI  - Human gene therapy.
AB  - Although gene therapy as a treatment for disease holds great promise, progress in
      developing effective clinical protocols has been slow. The problem lies in the
      development of safe and efficient gene-delivery systems. This review will
      evaluate the problems and the potential solutions in this new field of medicine.

PMID- 9579859
TI  - A different kind of wisdom.

PMID- 9579860
TI  - The legacy of Thomas Willis.

PMID- 9579861
TI  - Neurosurgical perspectives in pediatric neurooncology.
AB  - This communication describes one pediatric neurosurgeon's personal view of the
      neurosurgical perspectives in pediatric neurooncology. Various roles of surgery,
      including histological verification, maximum cytoreduction, neurodecompression
      and restoration of the cerebrospinal fluid pathway, are emphasized. A pediatric
      neurosurgeon, who is the first person to make decisions on diagnosis and
      treatment relating to children with brain tumors, should be up to date with
      advances in diagnostic and therapeutic methods. Particularly, he or she should be
      familiar with both the efficacy and the side effects of radiation therapy and
      chemotherapy to allow selection of the optimum treatment for such children.

PMID- 9579862
TI  - Late outcome of the surgical treatment of hydrocephalus.
AB  - The purpose of this report is to analyze the long-term outcome in hydrocephalic
      children treated by shunt placement and in particular their psycho-intellectual
      development. In the case of shunt placement postoperative mortality is virtually
      nil, and the overall mortality rate after 10 years of follow-up has been reduced
      to less than 5%. Morbidity, in contrast, is far from satisfactory. This study was
      conducted in 129 consecutive children with nontumorous hydrocephalus who
      underwent a first shunt insertion before the age of 2 years between 1979 and 1982
      and who were followed up for at least 10 years. The final neurological
      examination revealed a motor deficit in 60%, visual or auditory deficits in 25%,
      and epilepsy in 30%. The final IQs were above 90 in 32% of the children, between
      70 and 90 in 28%, between 50 and 70 in 19%, and lower than 50 in 21%. Integration
      into the normal school system was possible for 60% of the children, but half of
      them were 1-2 years behind their age group or having difficulties; 31% were
      attending special classes or were in institutions; and 9% were considered
      ineducable. The presence of behavioral disorders was a determinant factor for
      scholastic and social integration. Such disorders were frequent, and were
      characterized as severe in 30%. A relationship between final outcome and
      etiology, initial ventricular size, and epilepsy was observed. These results are
      used as the basis of a discussion on how morbidity might be improved.

PMID- 9579863
TI  - Endodermal cyst of the foramen magnum: case report and review of the literature.
AB  - The majority of endodermal cysts occur in the cervicothoracic spine, ventral to
      the cord. Intracranial locations are rare. We report a case involving the foramen
      magnum in a 14-year-old child, which was an incidental finding following a
      traumatic head injury. A review of the literature revealed six other cases
      involving this same location. These lesions are asymptomatic for a long time, and
      may cause brain stem medullary compression. Treatment is surgical. Effective
      simple removal can be achieved by a posterior approach.

PMID- 9579864
TI  - Immunohistochemical investigation on type III and VI collagen organization in
      human intervertebral discs in the neonatal period.
AB  - Nine L5-S1 discs from cadavers following death at ages ranging from 28 weeks of
      gestation to 1 month after birth were analysed immunohistochemically to
      investigate type III and VI collagen organization in neonatal discs. The annulus
      fibrosus stained poorly with the anti-type III antibody. The transition zone and
      the nucleus pulposus showed a fibrillary framework. No clear pericellular
      staining was detected. Poor staining with the anti-type VI antibody was detected
      in the annulus. Single pericellular rings were observed in the transition zone
      and in the nucleus. The pericellular rings were never multilayered. Type III and
      VI collagen organization in the newborn is similar to that observed in adults and
      in the aged. Multiple pericellular rings are never observed. Further research on
      diseased and healthy intervertebral discs may help clarify which disc changes are
      age-related and which follow on from degeneration.

PMID- 9579866
TI  - Reversible cerebral perfusion alterations in children with transient mutism after
      posterior fossa surgery.
AB  - Mutism is an infrequent and transitory complication observed following posterior
      fossa surgery. Patients become mute in the immediate postoperative period, with
      restoration of speech within a few weeks in the absence of additional
      neurological alterations. The anatomical structures thought to be involved are
      the connections between the cerebellar dentate nucleus, the ventrolateral nucleus
      of the contralateral thalamus and the supplementary motor area. In an attempt to
      understand the pathophysiology of this syndrome, and to depict the perfusion of
      different brain areas semiquantitatively, in two children who had become mute
      after posterior fossa surgery we performed a Tc99M-HM-PAO SPECT study during the
      period of mutism and again when normal speech had returned. In one patient, who
      had a left cerebellar astrocytoma, the SPECT study showed a marked reduction of
      cerebral perfusion in the right fronto-parietal region, and in the other, who had
      a medulloblastoma, a left fronto-temporo-parietal perfusion alteration was
      observed. When the patients regained normal speech, the follow-up SPECT studies
      revealed normalization of the cerebral perfusion. This study demonstrates the
      occurrence of a focal dysfunction of cerebral perfusion in children with
      cerebellar mutism after posterior fossa surgery. These observations are useful in
      extending our understanding of the pathophysiology of this postoperative clinical
      syndrome.

PMID- 9579865
TI  - Is the ancillary chemotherapy approach of any value in the treatment of
      infratentorial primitive neuroectodermal tumors with surgery and radiotherapy?
AB  - A retrospective historical analysis of patients under 18 years of age with the
      histopathological diagnosis of infratentorial primitive neuroectodermal tumor
      (PNET) is presented. The survey embraced two different groups of children. Group
      1 was defined as those patients treated from 1972 to 1984 with surgical resection
      plus neuraxis radiotherapy alone. Group 2 was made up of children treated from
      1990 to 1996 with the same approach but with the addition of adjuvant
      chemotherapy: cisplatin (day 1) and etoposide (days 1-3) every 3 weeks for 6
      months. Group 1 embraced 42 children with an age range of 1-16 years (mean 6
      years, SD 4.4 years). In group 2 there were 34 children, their ages ranging from
      1 to 18 years (mean 7.2, SD 4.6 years). The prevalence of stages T2M0 and T3M0
      was similar in both groups, but in group 1 there were 4 patients (9.5%) whose
      spinal fluid was positive for tumor cells (M1), while in group 2 there were 7
      children (20.5%) with positive spinal fluid. There was an unequivocal initial
      response to treatment in 86% of these children in group 1 and in 79% in group 2.
      The event-free survival (EFS) was 30% at 252 months in group 1, while for group 2
      the EFS was 67.6% at 63 months (P 0.002). Mortality from tumor activity was noted
      in 26 patients (70%) in group 1, while in group 2 mortality attributable to tumor
      progression was documented in 11 children (32%). We conclude that the use of
      adjuvant chemotherapy in these patients improves survival without any significant
      morbidity.

PMID- 9579867
TI  - Outcome of patients with meningomyelocele: the Ege University experience.
AB  - The medical records of 190 patients with meningomyelocele operated on between
      1979 and 1993 were reviewed. In 65 patients, psychometric tests were performed.
      The Denver Developmental Screening Test and the Wechsler Intelligence Scale for
      Children, Revised (WISC-R) were used in children under and over 6 years old,
      respectively. There were 82 boys (43.2%) and 108 girls (56.8%). The lumbar region
      was the site of the meningomyelocele in 113 patients (59.5%). Patients with
      cervical and sacral meningomyelocele had a higher rate of almost normal motor
      function than those with meningomyelocele at other levels (P=0.000). Only 36
      (21.7%) of 166 patients followed up by us did not have hydrocephalus. We also
      noted that the higher the location of the meningomyelocele, the greater the
      control of both sphincters (P=0.014). Fifty-four percent of the hydrocephalic
      patients had a normal development or IQ. Psychometric tests were normal in 76% of
      those without hydrocephalus. Twenty-four patients were lost to follow-up. The
      follow-up of the remaining 166 patients ranged from 1 month to 180 months (mean
      60.2 months). Fifty-three patients (32%) died, central nervous system infection
      being the most common cause of death (44%). The management of children with
      meningomyelocele needs a team approach.

PMID- 9579868
TI  - Pattern of electroencephalographic abnormalities in children with hydrocephalus:
      a study of 68 patients.
AB  - The pattern of electroencephalographic (EEG) abnormalities was studied in 68
      patients (41 male, 27 female, age range 1 month to 17 years) with hydrocephalus.
      They all had standardized EEG recordings, which were read by the same
      electroencephalographer. In 48 children the EEG was performed after ventriculo
      peritoneal shunting. The EEG abnormalities in the shunted group included slow
      waves in 26 patients [focal 2 (4.2%), generalized asynchronous 22 (45.8%),
      generalized synchronous 2 (4.2%)]; amplitude abnormalities in 2 (focal 1,
      generalized 1); epileptiform activity in 26 [partial 11 (22.9%), generalized 15
      (31.3%)] and hypsarrhythmia in 4 (8.3%). Only 4 (8.3%) traces were normal, giving
      an overall percentage abnormality of 92%. In the unshunted group generalized
      asynchronous slow waves were found in 12 patients (60%), generalized amplitude
      abnormality in 1, focal epileptiform activity in 3 (15%), and generalized
      epileptiform activity in 6 (30%); 2 tracings in this group were normal, giving an
      overall percentage abnormality of 90%. Hydrocephalus in children, regardless of
      the cause, may be associated with generalized or focal EEG abnormalities. This
      may reflect the heterogeneity of the neural generator in the underlying disease
      process.

PMID- 9579869
TI  - Intramedullary anaplastic oligodendroglioma in a child.
AB  - Primary intramedullary anaplastic oligodendroglioma is a rare tumor, only four
      cases of which have been reported. The authors present the case of a 38-month-old
      boy with primary intramedullary anaplastic oligodendroglioma. He underwent
      partial removal of the tumor and spinal radiation therapy. The residual tumor
      disappeared 12 months after radiation, and 48 months after treatment there was no
      evidence of recurrence. This case shows that in primary intramedullary anaplastic
      oligodendroglioma, postoperative radiation therapy confined to the spinal cord
      can yield an optimal result.

PMID- 9579870
TI  - Avulsed lumbar vertebral rim plate in an adolescent: trauma or malformation?
AB  - Avulsion of lumbar vertebral rim plate is an uncommon lesion, seen specially in
      young adults. Its occurrence in pediatric age is very infrequent. As with
      intervertebral disc herniation in children, an accurate diagnosis may be often
      delayed due to concerns for neoplasm, infection, and spondylolisthesis. We report
      a 15-year-old boy with symptoms and myelographic details of disc protrusion.
      Plain radiographs, computerized tomography of the lumbar spine, and operative
      findings showed that the cause of root compression was a slipping of the entire
      disc together with the posterior rim plate at the L4-5 space. Pertinent
      literature on the subject is briefly reviewed. The proposed mechanism for
      apophyseal ring fracture is a combination of two factors: congenital
      insufficiency of the rim plate and injury to the lumbar spine.

PMID- 9579871
TI  - Optic atrophy as the first symptom in Hallervorden-Spatz syndrome.
AB  - A 16-year-old boy with the classic or postinfantile type of Hallervorden-Spatz
      syndrome is described. Bilateral optic atrophy with visual loss but without
      retinal changes was the only presenting symptom. Mild cognitive impairment,
      behavioural disturbances and insidious extrapyramidal involvement appeared later.
      MRI showed marked symmetrical hypointensity of the globi pallidi and substantia
      nigra. This new observation suggests that the occurrence of optic atrophy in a
      patient with Hallervorden-Spatz syndrome should be regarded as noncoincidental
      and stresses the importance of an accurate neurological work-up in all
      adolescents with any unusual form of progressive optic atrophy.

PMID- 9579872
TI  - Cerebellitis presenting as acute hydrocephalus.
AB  - A 14-year-old boy presented acutely with occipital headache, nausea and vomiting.
      MRI showed obstructive hydrocephalus and marked bilateral cerebellar swelling
      with increased signal on T2-weighted imaging. Following treatment with oral
      corticosteroids, the clinical and radiological signs resolved. The clinical
      course and radiological appearances were consistent with cerebellitis associated
      with a significant mass effect and hydrocephalus.

PMID- 9579873
TI  - Meckel-Gruber syndrome.
AB  - Meckel-Gruber syndrome is a congenital disorder characterized by occipital
      encephalocele, polydactyly and polycystic kidneys. This rare syndrome has been
      reported in the literature as incompatible with life. We present the case of a
      newborn afflicted with the clinical triad of Meckel-Gruber syndrome. Appropriate
      treatment instituted in our case led to a good early outcome.

PMID- 9579875
TI  - Early circulating erythroid progenitor cells and expression of erythropoietin
      receptors in sickle cell disease.
AB  - The ability of circulating progenitor cells from 22 patients with sickle cell
      disease (SCD) to develop erythroid colonies was studied in vitro in the presence
      or absence of growth factors (5637-CM and erythropoietin). In both conditions,
      SCD patients presented significantly higher numbers of circulating burst-forming
      unit-erythroid (BFU-E/5x10[5]MNC) when compared to control subjects. The study of
      the expression of erythropoietin receptors revealed an increased level in SCD
      patients. Moreover, there was a correlation between both stimulated and autocrine
      (without stimulus) BFU-E and the expression of erythropoietin receptors. These
      results are of particular interest since they indicate that the phenomenon of
      spontaneous BFU-E-derived colonies observed in SCD patients may be due to an
      increased expression of erythropoietin receptors.

PMID- 9579876
TI  - Antibody-directed superantigen-mediated T-cell killing of myeloid leukaemic cell
      line cells.
AB  - Bacterial superantigens (SAgs) bound to MHC class II molecules on target cells
      are efficient activators of cytotoxic T cells expressing certain T cell receptor
      (TCR) Vbeta regions We described earlier that the specificity of the SAg
      Staphylococcus enterotoxin A (SEA) can be changed by introducing a D227A point
      mutation in the major MHC class II binding site and by genetically fusing the SEA
      mutant (SEAm) to protein A (PA). This SEAm-PA fusion protein can then be used to
      direct cytotoxic T cells to tumour cells coated with monoclonal antibodies
      (mAbs). In this communication, we tested the PA-SEAm fusion protein together with
      mAbs against the myeloid cell surface antigens CD13, CD15 and CD33. A SEA
      reactive T cell line was used as effector cells against 10 different myeloid
      leukaemic cell lines. Optimal lysis of antigen positive leukaemic cells was
      obtained at a PA-SEAm concentration of 1 ng/ml and effector : target cell ratios
      of 15 : 1. No correlation between target cell sensitivity and the level of
      surface antigen expression could be seen. The 6 acute myeloid leukaemia (AML)
      cell lines tested appeared to be more sensitive than the 4 chronic myeloid
      leukaemia (CML) cell lines. The sensitivity of the AML cell line HL-60 could be
      improved further by stimulation with TNFalpha. This was accompanied by increased
      surface ICAM-1 expression whereas specific target molecule expression (CD13,
      CD33) was unchanged. This suggests that sensitivity to lysis is related to the
      leukaemic subtype and ICAM-1 expression but not to the tumour antigen density.
      Our results show that it is possible to direct cytotoxic T cells to myeloid
      leukaemia cells by using SAgs linked to mAbs, and encourage the construction and
      testing of a recombinant direct SAg-mAb fusion protein as a candidate drug for
      therapy of myeloid leukaemias.

PMID- 9579874
TI  - Characterization of the ETO and AML1-ETO proteins involved in 8;21 translocation
      in acute myelogenous leukemia.
AB  - The AML1 and ETO genes are disrupted by the nonrandom chromosomal translocation
      t(8;21) in acute myelogenous leukemia (AML). While the AML1 gene encodes a
      transcription factor indispensable for definitive hematopoiesis, the biological
      function of ETO is unknown. To understand the role of ETO and AML1-ETO in the
      pathogenesis of AML, the full length cDNAs of ETO and AML1-ETO were cloned and
      antibodies against AML1 and ETO proteins have been developed in our laboratory.
      Western blot analysis showed that ETO and AML1-ETO were identified as 70 kDa and
      94 kDa proteins, respectively, and that both proteins, like AML1, were associated
      with the nuclear matrix. To examine whether the t(8;21)-positive AMLs expressed a
      94-kDa AML1-ETO, protein fractions isolated from leukemia blasts of 10 patients
      with t(8;21)-positive AML and the Kasumi-1 cells were analyzed by Western
      blotting. The 94 kDa AML1-ETO fusion protein was detected in all samples.
      However, this fusion protein was not detectable in all 40 patients with t(8;21)
      negative AMLs. The biological significance of AML1-ETO was examined in K562
      cells, which stably overexpress AML1-ETO. We found that AML1-ETO blocked the
      erythroid differentiation of K562 cells induced by low doses of Ara-C. Thus,
      t(8;21)-positive AMLs appear to overexpress the AML1-ETO fusion protein, which
      may be responsible for differentiation block and leukemogenesis in AML.

PMID- 9579877
TI  - Comparable TNF-alpha, IFN-gamma and GM-CSF production by purified normal marrow
      CD3 cells in response to horse anti-lymphocyte and rabbit antithymocyte globulin.
AB  - In vitro priming of T cell with horse antilymphocyte globulin (HALG) results in
      cytokine release, and this has been associated with its clinical efficacy in
      patients with severe aplastic anaemia (SAA). Rabbit antithymocyte globulin (RATG)
      has been studied less extensively. In this study we compare the in vitro priming
      effect of HALG and RATG on purified normal marrow T cells: end-points of the
      study were 1) levels of TNF-alpha (TNF-alpha), IFN-gamma (IFN-gamma) GM-CSF in T
      cell supernatants, and 2) effect of T cell supernatants on colony formation with
      or without exogenous GM-CSF TNF-alpha, IFN-gamma and GM-CSF levels were
      comparable for HALG, RATG and phytohaemagglutinin (PHA). T cell supernatants
      showed comparable enhancement of colony formation in the presence of recombinant
      human GM-CSF (rhGM-CSF) and supported colony forming unit granulomacrophage (CFU
      GM) growth in the absence of growth factor. This study shows that horse and
      rabbit derived ALG/ATG and PHA have a comparable in vitro priming effect on T
      cells: both agents should probably be tested for their clinical efficacy in SAA
      patients.

PMID- 9579878
TI  - Combined use of erythrocyte zinc protoporphyrin and mean corpuscular volume in
      differentiation of thalassemia from iron deficiency anemia.
AB  - In a retrospective study the diagnostic value of erythrocyte zinc protoporphyrin
      (ZPP) measurement as a means of distinguishing iron deficiency anemia from
      thalassemia syndromes in patients with microcytosis was explored. ZPP values were
      increased in all patients with iron deficiency and in part of the patients with
      thalassemia. The combined measurement of erythrocyte mean corpuscular volume
      (MCV) and ZPP resulted in a correct classification of patients with iron
      deficiency and with thalassemia in more than 95%. The predictive value of this
      method is better than the results obtained by using formulae derived from red
      cell indices. In population screening programs for thalassemia syndromes, in
      which MCV determination is used as the initial test, the ZPP test is recommended
      as a second test, in order to discriminate between patients with microcytosis due
      to iron deficiency and patients with microcytosis due to thalassemia syndromes.

PMID- 9579879
TI  - The estimation of efficacy of oral iron supplementation during treatment with
      epoetin beta (recombinant human erythropoietin) in patients undergoing cardiac
      surgery.
AB  - We estimated the efficacy of oral iron therapy during treatment with rhEPO in
      patients undergoing cardiac surgery who were contraindicated for autologous blood
      donation. Seventy-six patients were enrolled in this double-blind, placebo
      controlled trial and assigned to the 2 treatment groups (5x500 U/kg body weight
      rhEPO or placebo intravenously over 14 d before surgery). During the treatment
      period all patients received 300 mg Fe2+ (iron glycine sulfate) orally per day.
      rhEPO therapy produced significant increases in hemoglobin concentration (Hb),
      reticulocyte count, hematocrit (Hct) and the hypochromic red blood cells (HRBC),
      and a decrease in transferrin saturation (41%) compared to the placebo group
      before surgery. However, the preoperative increase in HRBC was independent of the
      baseline ferritin and even correlated positively with the preoperative increase
      in Hct (r=0.47, p<0.01). In rhEPO patients there were inverse correlations
      between baseline serum iron and the preoperative increases in Hb (r=-0.39,
      p<0.05), Hct (r=-0.50, p<0.01) and HRBC (r=-0.53, p<0.001). With this treatment
      regimen the HRBC appear to reflect the degree of erythropoietic stimulation
      rather than functional iron deficiency. The preoperative increases in
      reticulocytes, HRBC and Hb/Hct in patients with ferritin <100 mg/l or transferrin
      saturation <16% showed no significant difference compared to their complementary
      groups. The preoperative decrease in storage iron and the inverse correlation
      between the baseline ferritin and the preoperative change in ferritin (r=-0.94,
      p<0.0001) in the rhEPO group indicate that the iron requirement for hemoglobin
      synthesis is probably covered by the breakdown of stored iron and an increase in
      the rate of absorption of orally administered Fe2+. Intravenous rhEPO treatment
      with 5x500 U/kg body weight in combination with 300 mg oral Fe2+/d given over 14
      d before surgery is a suitable regimen to increase Hb by about 1.61 g/dl and Hct
      by 0.06.

PMID- 9579880
TI  - Trisomy 8 may not be related to the pathogenesis of myelodysplastic syndromes:
      disappearance of trisomy 8 in a patient with refractory anaemia without
      haematological improvement.

PMID- 9579881
TI  - Clinical features and prognostic factors of HIV-associated thrombotic
      microangiopathies.

PMID- 9579882
TI  - Vulnerable mutation Trp126-->stop of glycoprotein IX in Japanese Bernard-Soulier
      syndrome.

PMID- 9579883
TI  - Peripheral blood neutrophil count and candidacidal activity correlate with the
      clinical severity of sickle cell anaemia (SCA)

PMID- 9579884
TI  - Reintroduction of vitamin B12 in 2 patients with prior B12-induced anaphylaxis.

PMID- 9579885
TI  - Intravenous gammaglobulin therapy for acquired von Willebrand disease.

PMID- 9579886
TI  - Origins of the epileptic state.

PMID- 9579887
TI  - The new antiepileptic drugs: a systematic review of their efficacy and
      tolerability.
AB  - PURPOSE: Gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), topiramate (TPM),
      vigabatrin (VGB), and zonisamide (ZNS) are all in use as "add-on" treatment for
      patients with refractory epilepsy. There have been no comparative randomized
      controlled trials allowing an evidence-based choice between these drugs. We
      report a series of meta-analyses of randomized placebo-controlled add-on trials
      in which these drugs have been tested in patients with partial epilepsy. This
      work provides an estimate of each drug's efficacy and tolerability compared with
      placebo. These estimates are compared across drugs to give broad estimates of
      comparative efficacy and tolerability. METHODS: Trial reports were found by
      searching Medline, by searching through journals by hand, and by contacting the
      pharmaceutical industry. The outcomes chosen were the proportion of patients who
      (a) have a > or = 50% reduction in seizure frequency (50% responders); (b)
      withdrew from the study (any reason); or (c) reported the following side effects:
      ataxia, dizziness, fatigue, nausea, or somnolence. Overall odds ratio (OR) with
      95% confidence intervals (CIs; 50% responders) or 99% CIs; side effects) were
      calculated. RESULTS: Twenty-nine trials were included, representing 4,091
      randomized patients. The ORs for 50% response (95% CI) were GBP, 2.29 (1.53
      3.43); LTG, 2.32 (1.47-3.68); TGB, 3.03 (2.01-4.58); TPM, 4.07 (2.87-5.78); VGB,
      3.67 (2.44-5.51); and ZNS, 2.7 (1.36-4.47). ORs for discontinuation were GBP,
      1.36 (0.75-2.49); LTG, 1.19 (0.79-1.79); TGB, 1.81 (1.21-2.70); TPM, 2.56 (1.64
      4.00); VGB, 2.58 (126-5.27); and ZNS, 4.23 (1.71-10.49). CONCLUSIONS: We have
      clear evidence that each of these drugs is better than placebo at preventing
      seizures. When results are compared across drugs, the confidence intervals
      overlap, and we have no conclusive evidence of differences in efficacy or
      tolerability. Despite this, the agent that appears most effective may be twice as
      effective as the agent that appears least effective, and the agent that appears
      most likely to cause discontinuation may be 4 times more likely to do so than the
      treatment that appears least likely to do so. Comparative randomized studies are
      needed further to evaluate these drugs.

PMID- 9579888
TI  - Safety of long-term lamotrigine in epilepsy.
AB  - PURPOSE: To examine the safety of lamotrigine (LTG) used in general practice to
      treat epilepsy. METHODS: Information was collected on 11,316 patients who were
      included in a noninterventional observational cohort study conducted by means of
      Prescription-Event Monitoring (PEM). A follow-up study provided information on
      the first 3,994 patients who had taken LTG for > or = 6 months. Incidence density
      (ID) measurements were used to rank the frequency of the reported events.
      RESULTS: Rash was the most frequently reported nonepileptiform event (ID,
      19.7/1,000 patient-months) in the first month of treatment and resulted in LTG
      being stopped in 2% of the 11,316 patients. Rash was reported more frequently
      among children aged 2-12 years (ID, 29.4/1,000 patient-months) than adults. Other
      events associated with the use of LTG included headache, drowsiness, nausea,
      vomiting, malaise, and lassitude. Rare serious events possibly associated with
      LTG included 12 cases reported as Stevens-Johnson syndrome, four cases of
      neutropenia, three cases of thrombocytopenia, and two cases of disseminated
      intravascular coagulation. There were also individual cases of leucopenia, a
      meningitic reaction, acute renal failure, hepatotoxicity, and a "lupus-like"
      reaction possibly associated with the drug. No foetal abnormalities were
      specifically associated with the use of the drug in pregnancy. No death was
      attributed to LTG. CONCLUSIONS: Patients had severe epilepsy, inadequately
      controlled by other antiepileptic agents. The results of these two studies
      suggest that LTG is acceptably safe when used for the treatment of refractory
      epilepsy.

PMID- 9579890
TI  - Anticonvulsant action of gabapentin during postnatal development in rats.
AB  - PURPOSE: To study the anticonvulsant effects of gabapentin (GBP) in immature
      animals. METHODS: Motor seizures were induced by pentylenetetrazol in 7-, 12-, 18
      , 25-day-old, and adult rats. Animals pretreated with GBP (15, 30, or 60 mg/kg
      i.p.) were compared with controls. The incidence and latency of two types of
      seizures [minimal (i.e., clonic)] and generalized tonic-clonic (GTCS) were
      recorded, and seizure severity was scored. RESULTS: GBP suppressed or at least
      restricted the tonic phase of GTCS at all the developmental stages studied. In
      addition, minimal seizures were suppressed in 18-day-old rats. Both effects
      exhibited a tendency to a U-shaped dose-response curve. CONCLUSIONS:
      Anticonvulsant effects of GBP were demonstrated in immature and in adult rats.

PMID- 9579889
TI  - Tolerability and pharmacokinetics of monotherapy felbamate doses of 1,200-6,000
      mg/day in subjects with epilepsy.
AB  - PURPOSE: Felbamate (FBM) pharmacokinetic parameters, safety and tolerability in
      the dose range of 1,200-6,000 mg/day were assessed in two open-label studies with
      similar designs. METHODS: In study A, newly diagnosed subjects with epilepsy
      receiving FBM monotherapy at a starting dose of 1,200 mg/day (400 mg/three times
      daily, t.i.d.) and increased 1,200 mg/day, if tolerated, at 14-day intervals to
      3,600 mg/day were investigated. In study B, epilepsy subjects with prior FBM
      monotherapy exposure received ascending FBM doses in five consecutive 14-day
      periods with a starting dose of 3,600 mg/day (1,200 mg t.i.d.) FBM. In each
      successive period, if FBM was well tolerated, the dose was increased by 600
      mg/day to a maximum of 6,000 mg/day (2,000 mg t.i.d.). RESULTS: The
      pharmacokinetic parameter estimates maximum observed concentration (Cmax), area
      under the concentration-time curve (AUCtau) Ctrough, and Cav showed a linear
      dependence to dose above the 1,200-6,000 mg/day FBM dose range (F-tests; p <
      0.0001) with apparent clearance (Cl/kg) and Tmax (time to Cmax) independent of
      dose. When AUCtau, Cmax and Ctrough were adjusted for dose, there were no
      significant differences between the dosing periods. CONCLUSIONS: The data
      establish that plasma concentrations of FBM are linear with respect to dose to
      6,000 mg/day. In addition, FBM was safely administered at these doses for periods
      as long as 14 days to epileptic subjects with prior exposure to FBM. FBM-naive
      subjects appeared to report more adverse experiences (generally of mild to
      moderate severity) than did subjects with prior FBM exposure.

PMID- 9579891
TI  - Role of the claustrum in convulsive evolution of visual afferent and partial
      nonconvulsive seizure in primates.
AB  - PURPOSE: We tested cross-species validity of the role of the claustrum in the
      convulsive evolution of the visual afferent and amygdaloid seizure and the
      specificity of the claustral lesioning effect. METHODS: In 7 Senegalese baboons,
      we examined the effect of unilateral claustral lesioning on generalized
      convulsive seizures either kindled from the amygdaloid nucleus (AM) and cingulate
      cortex (CG) or induced by intermittent photic stimulation (IPS) after systemic
      administration of D,L-allylglycine (AG). RESULTS: A lesioned area common to all
      animals was the anterior half of the left claustrum. Postoperative restimulation
      of the kindled left AM or CG evoked only nonconvulsive seizures. When few
      convulsive seizures emerged in 1 CG-kindled animal, they were mirror image of the
      kindled seizure and arose from the nonlesioned right hemisphere. Restimulation of
      the kindled right AM or CG reactivated kindled seizures. An IPS-induced
      generalized convulsive seizure was transformed into a secondarily generalized
      seizure arising from the nonlesioned right hemisphere. CONCLUSIONS: The primate
      claustrum regulates the convulsive evolution of partial seizures originating from
      nonmotor structures such as the AM and CG and also regulates the convulsive
      development that follows IPS. Our findings suggest that predisposed
      susceptibility expressed at the claustrum may be involved in the clinical
      variation with respect to convulsive evolution of nonmotor partial seizures and
      convulsive susceptibility to IPS in human primates.

PMID- 9579892
TI  - In whom does status epilepticus occur: age-related differences in children.
AB  - PURPOSE: Status epilepticus (SE) is an uncommon but potentially life-threatening
      seizure. It is most common in children. Little is known about the differences
      within the pediatric age group in terms of the type of patient seen with SE.
      METHODS: We analyzed the records of 394 children aged 1 month to 16 years who
      were part of two large studies of pediatric SE conducted in Bronx, New York, and
      Richmond, Virginia. The 394 children had a mean age of 4.4 years and included 349
      (89%) with an initial episode of SE. RESULTS: Status epilepticus was most common
      in younger children with >40% of cases occurring in those younger than 2 years.
      The distribution of causes was highly age dependent. More than 80% of children
      younger than 2 years had SE of febrile or acute symptomatic origin, whereas
      cryptogenic and remote symptomatic causes were most common in older children (p <
      0.001). One hundred fifty-eight (40%) of the cases were known to be previously
      neurologically abnormal, including 35 (21%) of 169 younger than age 2 years and
      123 (55%) of 225 older than 2 years (p < 0.001). One hundred seventy-seven (45%)
      children had a history of seizures including 142 (41%) of the 349 children with a
      first episode of SE. A history of seizures was present in 34 (20%) of those
      younger than 2 years and 143 (64%) of those older than 2 years (p < 0.001). The
      effect of age remained significant even when the analysis was limited to those
      with SE of cryptogenic or remote symptomatic origin. CONCLUSIONS: There is a
      strong effect of age on the frequency and etiology of SE, as well as on the type
      of child who has SE. In young children, SE occurs primarily in children who are
      neurologically normal and with no history of unprovoked seizures. In older
      children, SE occurs primarily in those who are known to have prior unprovoked
      seizures and who are often also neurologically abnormal.

PMID- 9579893
TI  - Partial cosegregation of familial hemiplegic migraine and a benign familial
      infantile epileptic syndrome.
AB  - PURPOSE: We studied a large Dutch-Canadian family, in which two very rare
      hereditary paroxysmal neurologic disorders, familial hemiplegic migraine (FHM)
      and a "benign familial infantile epileptic syndrome" concur and partially
      cosegregate. FHM is a dominantly inherited subtype of migraine with attacks of
      hemiparesis, linked to chromosome 19p13 in 50% of the families tested. Recently
      mutations in a brain-specific P/Q-type Ca2+ channel alpha1 subunit gene
      (CACNL1A4) were identified in families with chromosome 19-linked FHM. The
      infantile epileptic syndrome resembles to two other dominantly inherited benign
      epilepsies occurring in the first year of life, benign familial neonatal
      convulsions (BFNC), assigned to chromosomes 20q13.2 and 8q, and benign infantile
      familial convulsions (BIFC), as yet unlinked. METHODS: Linkage analysis was
      performed for the known locations of FHM and BFNC. The question whether the two
      conditions in this family can be caused by a single gene defect was addressed by
      additional linkage analysis. RESULTS: We excluded linkage of the infantile
      convulsions to markers on chromosome 20q13.2, 8q, or 19p13. This indicates the
      existence of a third locus for benign familial convulsions in the first year of
      life. Linkage of FHM to these markers was not formally excluded but seems very
      unlikely. Statistical analysis of whether, in this family, both conditions are
      caused by a single gene defect was inconclusive. CONCLUSIONS: We describe a
      "benign familial infantile epileptic syndrome" with attacks of FHM at a later
      age. Further genetic studies in this family may help to unravel the genetic basis
      of epilepsy or migraine or both.

PMID- 9579894
TI  - Safety of intrahippocampal depth electrodes for presurgical evaluation of
      patients with intractable epilepsy.
AB  - PURPOSE: Intracerebral depth electrodes are used in preoperative evaluation of
      selected patients with intractable epilepsies. In spite of their usefulness,
      safety of depth electrodes is disputed, and the number of insertions is
      decreasing. This study examined retrospectively possible deleterious effects such
      as perioperative complications, induction of epileptogenesis, and
      neuropsychologic deficits. METHODS: Clinical course and neuroradiologic findings
      of 115 patients with bilaterally inserted longitudinal intrahippocampal depth
      electrodes (IDEs) were analyzed. Hippocampal resection specimens were examined
      histopathologically. To detect newly developed epileptogenic areas, EEG
      recordings, seizure control, and semiology after standardized resection
      procedures were compared between patients who received IDEs and those who did
      not. To demonstrate functional deficits caused by IDE insertion into an
      unaffected hippocampus of the speech-dominant hemisphere, changes of verbal
      learning and memory performances before and after right amygdalohippocampectomy
      were compared between patients evaluated with and without IDEs. RESULTS: Five
      significant complications without any permanent neurologic deficit were noted,
      and only one was specifically linked to IDE insertion. The tissue damage
      associated with the insertion was minimal and sharply circumscribed. No
      differences of seizure outcome after standardized resections were identified
      between patients with and without IDEs. In postoperative EEG recordings, there
      was no evidence of new epileptogenic areas. No verbal memory deficit caused by
      IDE implantation into the hippocampus of the speech-dominant hemisphere was
      detectable. CONCLUSIONS: Results indicate that it is safe to implant these IDEs
      in selected patients.

PMID- 9579895
TI  - Stereotactic amygdalohippocampotomy and mesial temporal spikes.
AB  - PURPOSE: To investigate the mechanism of mesial temporal spike generation, we
      sought to determine whether amygdalohippocampotomy by radiofrequency lesions
      altered spike rates in patients with medically intractable temporal lobe
      epilepsy. METHODS: The subjects were 14 patients whose ictal semiology, ictal and
      interictal EEGs, and neuropsychological profile were compatible with seizure
      origin from MRI-demonstrated unilateral mesial temporal sclerosis. Mesial
      temporal spikes were recorded by a multicontact electrode line stereotactically
      placed in the temporal horn of the lateral ventricle. A recording and lesioning
      electrode was also stereotactically advanced to multiple amygdala and hippocampal
      targets. Several confluent (9 patients) or discrete (5 patients) radiofrequency
      lesions were made in the amygdala and anterior hippocampus. Scalp and invasive
      recordings were performed before lesioning, between each lesioning process, and
      for 48 postoperative h. RESULTS: As compared to prelesion recordings, no
      consistent change in anterior and total mesial temporal spike rates occurred
      intraoperatively or postoperatively. Postlesion: prelesion spike ratios failed to
      correlate with effectiveness of lesionectomy for seizure control. In contrast,
      complex partial seizures improved in 13 of 14 patients. CONCLUSIONS: Amygdala and
      hippocampal destructive lesions had no consistent effect on meisal temporal spike
      quantity, but reduced temporal lobe CPS in 13 of 14 patients. This dichotomy
      suggests that CPS may result from concerted epileptogenesis of the hippocampus,
      entorhinal cortex, and possibly the amygdala, while the entorhinal cortex alone
      can produce interictal spikes.

PMID- 9579896
TI  - Seizure lateralization during EEG monitoring in patients with bilateral foci: the
      cluster effect.
AB  - PURPOSE: To determine whether seizures that occur in clusters are more likely to
      reflect activity of the same focus than are seizures that are widely separated in
      time. METHODS: EEG monitoring data from 14 patients with bilateral independent
      seizure onsets were analyzed. Twelve of the 14 patients had surface recordings
      only, and two had implanted electrodes. Interseizure intervals (ISIs) for 151
      seizure pairs were measured. Seizure onsets were classified as right hemispheric,
      left hemispheric, or indeterminate. Seizure pairs were classified as concordant
      for hemisphere of onset, discordant, or indeterminate. The relation between
      seizure-pair concordance and ISI was examined by using univariate analysis and
      analysis of variance (ANOVA). RESULTS: Both seizures originated from the same
      hemisphere in 61 (75%) of 81 seizure pairs with ISIs <8 h, compared with 28 (55%)
      of 51 seizure pairs with ISIs >8 h (p < 0.015). The cluster effect was not more
      pronounced for ISIs <2 h. ANOVA demonstrated that the relation between ISI and
      seizure concordance was not a result of the variability in seizure rates among
      patients. In three patients, the presence of bilateral foci was not demonstrated
      until more than five seizures were recorded. CONCLUSIONS: Seizures that occur
      after an ISI of <8 h are more likely to come from the same side as the previous
      seizure than are those with longer ISIs. Thus clustered seizures should not be
      given the same weight as seizures widely separated in time. In addition, more
      than five seizures may sometimes be needed to adequately assess patients being
      evaluated for epilepsy surgery.

PMID- 9579897
TI  - Movement-induced seizures: a case report.
AB  - Reflex seizures induced by movement are typically evoked by sudden or unattended
      motor actions. However, tonic seizures may also be triggered by slow movements as
      observed in nonketotic hyperglycemia or in "praxis-induced epilepsy." We report
      the case of a young, nondiabetic patient affected by recurrent partial tonic
      postural seizures precipitated by slow movements which were unrelated to
      cognitive tasks. Ictal EEG did not permit location of the epileptogenic brain
      region. However, the clinical features suggest possible involvement of the
      supplementary motor area.

PMID- 9579898
TI  - De novo aphasic status epilepticus.
AB  - The literature contains only a handful of reports of patients with aphasia as the
      principal or only obvious manifestation of partial status epilepticus. Even fewer
      patients of this type have been well documented both clinically and by ictal EEG
      monitoring. We studied an otherwise healthy woman with abrupt onset of aphasia
      initially thought to be the result of an infarct of the left temporoparietal
      area. We were able to document partial status epilepticus involving the left
      temporoparietal area with EEG/video monitoring and showed rapid reversal of the
      aphasic disorder with antiepileptic drug (AED) treatment. The case is presented
      with a review of previous reports to underscore the importance of considering
      this diagnosis in patients with abrupt onset of aphasia.

PMID- 9579899
TI  - Successful treatment by direct hemoperfusion of coma possibly resulting from
      mitochondrial dysfunction in acute valproate intoxication.
AB  - PURPOSE: We evaluated the efficacy of direct hemoperfusion (DHP) for treatment of
      acute valproate (VPA) intoxication and speculate on the biochemical perturbations
      that suggest a mechanism of coma induced by VPA overdose. PATIENT AND METHODS:
      The comatose patient was hospitalized approximately 6 h after ingesting 18 g VPA.
      DHP, with 200 g activated charcoal, was performed for 6 h. The plasma
      concentrations of VPA and Glasgow coma scale scores after admission were
      estimated. Before and after DHP, urine samples were tested in serial fashion for
      VPA metabolites, organic acids, and acyl carnitine esters of fatty acids.
      RESULTS: Plasma VPA was efficiently adsorbed on activated charcoal. The patient's
      plasma concentration of VPA decreased from 471 microg/ml (2,830 microM) to 45
      microg/ml (270 microM), at which point the patient became alert. The half-life
      (t1/2) of VPA was calculated as 4.4 h before DHP and as 1.8 h during DHP. Before
      DHP, lactate and VPA-glucuronide markedly increased in urine samples, but beta
      keto-VPA, a major mitochondrial metabolite, was not detected. Urinary excretion
      of carnitine esters of medium chain (C8-C10) dicarboxylic acids was increased.
      After DHP, lactate and VPA-glucuronide decreased, but a significant amount of
      beta-keto-VPA was demonstrated. Carnitine esters of medium chain dicarboxylic
      acids were decreased. CONCLUSIONS: DHP with activated charcoal was effective
      treatment for the patient with acute VPA intoxication and coma. The onset of coma
      may have been related to inhibition of beta-oxidation in the mitochondria, which
      was reversible by elimination of plasma VPA by DHP.

PMID- 9579900
TI  - The ketogenic diet revisited: back to the future.

PMID- 9579901
TI  - Ketogenic diet: effects on expression of kindled seizures and behavior in adult
      rats.
AB  - PURPOSE: Despite use of the ketogenic diet (KD) for >75 years its effectiveness
      or mechanism of action has been examined in few animal studies. Using the
      kindling model of epilepsy, we tested the anticonvulsant effectiveness and
      behavioral consequences of an experimental KD in adult rats. METHODS: Rats fully
      kindled from the amygdala were divided into KD-fed or standard rat diet-fed
      groups; diet treatment continued for 5 weeks. The KD approximated at 4:1
      ("classic") ketogenic diet and consisted (by weight) of 70% fat, 14% protein, no
      carbohydrate, and appropriate vitamins, minerals and fiber; 92% of energy
      provided was contributed by fat and 8% was contributed by protein. Afterdischarge
      threshold and duration (ADT, ADD) and stage 5 seizure threshold and duration (ST,
      SD) were assessed weekly for 5 weeks. During week 3, learning and memory were
      tested by the water maze and the behavioral response to a novel environment was
      assessed by the open field test. RESULTS: Rats receiving the KD became ketonemic
      and had weight gains similar to those of control rats. As compared with rats
      receiving a standard diet, those fed the KD had an elevated ADT and ST for the
      first 2 weeks of treatment. The control and KD-fed groups did not differ with
      regard to ADD or SD at any time during the study, and both groups performed
      similarly in the water maze and open field test. CONCLUSIONS: In the kindling
      model, the KD afforded transient protection against the focal generation of
      kindled seizures but not seizure spread. Rats that received the KD did not
      perform differently from control-fed rats on spatial learning or exploratory
      behavior tasks. Our results provide a promising model for study of the
      anticonvulsant mechanisms of ketosis.

PMID- 9579902
TI  - Direct gene transfer into human epileptogenic hippocampal tissue with an adeno
      associated virus vector: implications for a gene therapy approach to epilepsy.
AB  - PURPOSE: Virus vectors capable of transferring genetic information into human
      cells provide hope for improved therapy in several neurological diseases,
      including epilepsy. We evaluated the ability of an adeno-associated virus (AAV)
      vector to transfer and cause expression of a lacZ marker gene in brain slices
      obtained from patients undergoing temporal lobectomy for control of medically
      intractable seizures. METHODS: Human brain slices were injected with an AAV
      vector (AAVlacZ) encoding Escherichia coli beta-galactosidase and incubated for
      as long as 24 h. The presence of lacZ mRNA. beta-galactosidase protein and
      enzymatic activity were assayed by reverse transcriptase polymerase chain
      reaction (rtPCR), immunocytochemistry, and the X-Gal technique, respectively.
      RESULTS: AAVlacZ directed the expression in human epileptogenic brain of E. coli
      beta-galactosidase that had functional activity. Expression was observed in < or
      =5 h and was sustained for as long as the slices were viable. Morphological
      analysis indicated that neurons were preferentially transfected, and there was no
      evidence of cytotoxicity. CONCLUSIONS: Our results confirm the feasibility of
      using AAV vectors to transfer genes into the human CNS and in particular, into
      neurons. Replacement of the lacZ gene with a functional gene modulating
      hippocampal neuronal physiology, might allow a localized genetic intervention for
      focal seizures based on the stereotaxic or endovascular delivery of such a vector
      system into the appropriate brain region.

PMID- 9579903
TI  - Convulsant action of D,L-homocysteic acid and its stereoisomers in immature rats.
AB  - PURPOSE: We wished to characterize the convulsant effect of homocysteic acid
      (HCA) in developing rats. METHODS: Seizures were induced in 7-, 12-, 18-, and 25
      day-old rats by intraperitoneal (i.p.) administration of D,L-HCA and in 12-day
      old rats by i.p. injection of L- and D-stereoisomers of HCA. The animals were
      observed for 30 min after injection. The incidence, latencies, pattern of motor
      seizures, and all behavioral phenomena were noted. Fifty percent convulsant dose
      (CD50) values were calculated by probit analysis. Electrocorticograms (ECoG) were
      recorded after injection. RESULTS: HCA did not elicit minimal clonic seizures
      whereas generalized tonic-clonic seizures (GTCS) occurred in all the age groups
      studied. Flexion (emprosthotonic) convulsions occurred to postnatal day 18. ECoG
      recordings exhibited delta activity in younger pups and sharp graphoelements in
      older pups, but electroclinical correlation was poor. Young animals were more
      sensitive to the convulsant effect of D,L-HCA. In addition, D-HCA was
      significantly more effective than L-HCA in inducing both flexion and generalized
      seizures. CONCLUSIONS: Our data clearly indicate that seizures induced by HCA
      differ from those evoked by homocysteine. There are no qualitative differences in
      the motor pattern of seizures induced by the two stereoisomers of HCA, but marked
      differences were apparent in the very first signs of their action. These
      differences might be due to interaction with different glutamate receptor
      subtypes.

PMID- 9579904
TI  - Adolescent onset of idiopathic photosensitive occipital epilepsy after remission
      of benign rolandic epilepsy.
AB  - PURPOSE: We describe 2 girls, aged 19 years, who experienced a rolandic seizure
      at ages 4 and 5, respectively, together with the interictal EEG features of
      benign rolandic epilepsy (BRE). In adolescence both patients developed
      photosensitive occipital seizures accompanied by spontaneous and photic-induced
      occipital EEG paroxysms. METHODS: We have been following 33 patients with a
      history of BRE, between ages 12 and 28 years (mean 17 years). Twenty-one of these
      patients had experienced their last rolandic seizure before the age of 10 years
      and 9 of them had been without treatment since age 11 or earlier. In 2 of these 9
      patients, other types of seizures recurred after remission of BRE. Clinical, EEG,
      and evoked potential findings on these 2 patients are presented. RESULTS: After
      having experienced BRE, both patients suffered partial seizures from age 12, with
      elementary visual hallucinations, visual blurring, slow head turning, cephalic
      pain, epigastric discomfort, unresponsiveness, and vomiting. Seizure onset was
      related to watching TV or exposure to bright light. EEG showed interictal
      occipital spikes, and a photoparoxysmal response limited to the occipital lobes.
      Visual evoked potentials were greatly increased in amplitude. One patient had two
      visual attacks only and remained seizure free after 4 years of follow-up, while
      the other had seizures controlled by an association of valproate and
      carbamazepine. CONCLUSIONS: Clinical and neurophysiological characteristics
      suggest that these two patients may have presented different age-related
      expressions within the spectrum of a benign seizure susceptibility syndrome
      rather than sharply distinct epilepsy syndromes.

PMID- 9579905
TI  - Benign childhood epilepsy with centrotemporal spikes and electroencephalography
      trait are not linked to EBN1 and EBN2 of benign neonatal familial convulsions.
AB  - PURPOSE: The electroencephalographic hallmark of benign childhood epilepsy with
      centrotemporal spikes (BECTS, or rolandic epilepsy) are characteristically shaped
      centrotemporal spikes and sharp waves (CTS). This EEG trait, but not BECTS
      itself, has been reported to follow an autosomal dominant mode of inheritance
      with incomplete penetrance and age dependence. CTS therefore represents a
      neurobiologic marker for the increased risk of developing BECTS. Benign neonatal
      familial convulsions (BNFC) like BECTS is an idiopathic age-dependent epilepsy
      with a benign course. Observations of benign neonatal seizures and BECTS in the
      same individual are well documented. Neonatal seizures with benign course were
      found in increased numbers in a series of CTS carriers. Two genetic loci, EBN1
      and EBN2, have been mapped in families with BNFC, making these two loci strong
      candidates for the CTS trait underlying BECTS. The aim of this study was to
      determine whether these two epilepsy syndromes are allelic disorders. METHODS:
      Linkage analysis was performed in 12 families with probands with BECTS and one or
      more relatives with CTS in the EEG with or without BECTS by using polymorphic DNA
      markers. RESULTS: Assuming an autosomal mode of inheritance with penetrances of
      0.9 and 0.45, respectively, both loci were consistently excluded. CONCLUSIONS:
      The CTS trait and EBN1 and EBN2 segregate independently. BECTS and BNFC therefore
      appear to be genetically distinct entities. Benign neonatal seizures may be a
      underrecognized symptom of the CTS trait itself.

PMID- 9579906
TI  - Children with focal sharp waves: clinical and genetic aspects.
AB  - PURPOSE: To investigate the spectrum of clinical manifestations in children with
      benign focal sharp waves in the EEG to gain further insight into the genetic
      background of clinical and EEG symptomatology in a family study. METHODS: All 147
      children (134 with seizures, 13 without) met the following inclusion criteria:
      (a) at least one EEG with focal sharp waves characteristic of benign partial
      epilepsies, and (b) at least 1 sibling investigated by EEG. The families were
      questioned orally or in writing regarding the occurrence of seizures. Patients'
      records were evaluated by a standardized scheme. RESULTS: The following types of
      seizures occurred: febrile convulsions (FC), afebrile generalized tonic-clonic
      seizures (GTCS), simple and (rarely) complex partial seizures; and rolandic
      seizures in the strict sense. Neonatal seizures were overrepresented (6%); there
      were no indications of lesional causes. FC occurred in 38 children (26%). As
      compared with unselected cases of FC, complex symptoms were overrepresented.
      Family data suggested a maternal preponderance in the transmission of FC
      liability. Affected relatives of FC probands manifested FC more often than did
      relatives of probands without FC. Families of 32 patients with typical rolandic
      seizures (24% of the 134 probands with seizures) showed no aggregation of
      rolandic epilepsy, but did show variable seizure types. In the entire sample, EEG
      investigations showed focal sharp waves in 11% of siblings aged 2-10 years. No
      relation existed between clinical symptomatology and sharp wave findings in
      siblings. In 66% of probands, the EEG disclosed generalized genetic patterns.
      Siblings with generalized spike-waves (sw) and/or theta rhythm had focal sharp
      waves more often than those without sw and/or theta rhythm. CONCLUSIONS: The
      phenotypic expression of the genetic anomaly underlying focal sharp waves shows
      considerable variability. The clinical and EEG findings are in agreement with a
      multifactorial pathogenesis of epilepsies with "benign" focal epileptiform sharp
      waves.

PMID- 9579907
TI  - Consistent EEG focalities detected in subjects with primary generalized
      epilepsies monitored for two decades.
AB  - PURPOSE: To describe the evolution of interictal findings in serial EEGs from
      patients with primary generalized epilepsy. METHODS: A cohort of 89 subjects with
      various primary generalized epilepsies were reviewed. Thirty-one did not meet a
      priori criteria. Of the 58 patients analyzed, 12 had only absence seizures, 28
      had absence seizures followed by one or more generalized tonic-clonic seizures, 9
      had generalized tonic-clonic seizures followed by absence and/or myoclonic
      seizures. and 9 had juvenile myoclonic epilepsy. Patients were followed for a
      mean of 16 years. An average of 39 EEGs were obtained on each patient. RESULTS:
      Thirty-two patients (56%) had focal features present in up to 65% of the EEGs in
      each of the patients. Accepted focalities were only those that were consistent in
      lateralization, location and, often, morphology across the span of the study.
      Focal findings were most often temporal or frontal. CONCLUSIONS: Patients with
      typical primary generalized epilepsies show a high incidence of focal EEG
      features that cannot be explained on the basis of structural lesions,
      coincidental factors, or to artifacts of the selection criteria. Although the
      data do not allow a definitive explanation, possible mechanisms include
      associated focal cortical pathology such as microdysgenesis, and development over
      time of localized, self-sustaining hyperexcitability in low-threshold cortical
      structures subjected to repeated generalized spike-wave activity. Either
      hypothesis implies the participation and interaction of genetic, ontogenic, and
      environmental factors.

PMID- 9579908
TI  - Atonic epileptic drop attacks associated with generalized spike-and-slow wave
      complexes: video-polygraphic study in two patients.
AB  - PURPOSE: We studied falling manifestations of atonic epileptic drop attacks
      (AEDA) in 2 patients with cryptogenic epilepsy with myoclonic-astatic seizures.
      METHODS: Using video-polygraphic examinations. For analysis, we recorded 51
      seizures in 1 patient and 18 seizures in the other. The extent of AEDA ranged
      from collapsing and landing on the buttocks to head nodding only without falling.
      RESULTS: Detailed video analysis of the drop attacks, with the patient in
      standing position, demonstrated the first manifestations to be flexion at the
      waist and knees, followed by further knee flexion, leading to falling straight
      down and landing on the buttocks. Ictal polygraphs demonstrated diffuse
      interruptions of ongoing EMG discharges corresponding to the falls, indicating
      that these attacks are true atonic seizures. CONCLUSIONS: The falling
      manifestations of AEDA appeared to be characteristic and different from those of
      tonic drop seizures, which have been described as falling forward with tonic
      flexion of the hips, upper trunk, and head, as well as abduction or elevation of
      the arms.

PMID- 9579909
TI  - Negative myoclonic status due to antiepileptic drug tapering: report of three
      cases.
AB  - PURPOSE: Epileptic negative myoclonus (ENM) has been increasingly recognized in
      different epilepsies, but the reasons for its appearance and prognosis remain
      uncertain. We report 3 patients who developed de novo, almost continuous ENM,
      triggered by antiepileptic drug (AED) tapering, that resolved with treatment.
      METHODS: Three patients aged 16, 19, and 65 years with a 13- to 36-year history
      of partial epilepsy were receiving a therapeutic dosage of carbamazepine or
      phenobarbital plus either clobazam (CLB) or valproate (VPA). None had previously
      had ENM. Forty-eight to 72 h after CLB or VPA withdrawal, the habitual seizures
      recurred. The patient also began to report repetitive postural lapses of one or
      more limbs that interfered with eating or writing. At this time, each patient
      underwent polygraphy with simultaneous surface electromyography (EMG) of deltoid,
      biceps, and triceps muscles and of the wrist extensor and flexor bilaterally.
      RESULTS: In all patients, EEGs demonstrated almost continuous epileptiform
      discharges whose spatial distribution was similar to that observed before ENM
      appearance. Polygraphic recordings showed repetitive loss of postural EMG
      activity in one or more limbs, 100-400 ms in duration, which occurred in
      conjunction with the spike-waves. One milligram of clonazepam intravenously
      always terminated ENM status, which has not recurred in the ensuing 9-36 months.
      CONCLUSIONS: ENM may emerge as a new type of seizure due to tapering of AED
      therapy. This effect is possibly related to the great activation of epileptiform
      activity with consequent interference with cortical activity.

PMID- 9579910
TI  - Reproduction among individuals with idiopathic/cryptogenic epilepsy: risk factors
      for spontaneous abortion.
AB  - PURPOSE: We wished to determine the effects of seizure type, age at onset, and
      family history of epilepsy on risk of spontaneous abortion in the pregnancies of
      adults with idiopathic/cryptogenic epilepsy. METHODS: We examined pregnancy
      outcomes in 812 adults with idiopathic/cryptogenic epilepsy who had ever had or
      fathered a pregnancy and 250 of their same sex siblings who had ever had or
      fathered a pregnancy. We compared the likelihood of spontaneous abortion before
      and after onset of epilepsy with the likelihood of spontaneous abortion among
      same sex siblings. RESULTS: Risk of spontaneous abortion was not increased before
      onset of epilepsy. After onset of epilepsy, risk of spontaneous abortion was
      significantly increased in the pregnancies of wives of men who had localization
      related epilepsy with age at onset <10 years or who did not have a family history
      of epilepsy. In women after onset of epilepsy, risk of spontaneous abortion was
      significantly increased for pregnancies of women with localization-related
      epilepsy with age at onset < or =20 years and for those of women with or without
      a family history of epilepsy. Risk of spontaneous abortion was greatest in the
      pregnancies of women with a positive family history of epilepsy odds ratio, (OR =
      2.12, p < 0.05). CONCLUSIONS: Risk of spontaneous abortion in the pregnancies of
      men and women with idiopathic/cryptogenic epilepsy varied with the clinical
      characteristics of their epilepsy. The increased risk of spontaneous abortion in
      women with a family history of epilepsy may influence the observed risk of
      epilepsy in their live-born offspring.

PMID- 9579911
TI  - Health-related quality of life after epilepsy surgery: a Swedish multicenter
      study.
AB  - PURPOSE: To investigate health-related quality of life (HRQOL) in relation to
      seizure outcome as part of a multicenter follow-up of epilepsy surgery in Sweden.
      METHODS: A battery including the SF-36 Health Survey and the Hospital Anxiety and
      Depression scale (HAD) was distributed to all patients older than 16 years. Mean
      follow-up time was 4 years (range, 2-13 years) and response rate, 91% (103 of 113
      patients). HRQOL data were related to seizure frequency and severity (Chalfont
      Seizure Severity Scale). RESULTS: Seventy-six percent considered their global
      health to be better than it was before surgery. Degree of improvement in seizure
      control correlated with improved satisfaction with health (Spearman's r = 0.44).
      Higher SF-36 scores (higher HRQOL ratings) correlated with percentage reduction
      of seizure frequency for all scales and was strongest for perception of general
      health (Spearman's r = 0.46). When the patients were divided into four categories
      [A, completely seizure free (n = 29); B, seizure free with aura (n = 18); C, > or
      =75% reduction in seizure frequency (n = 24); and D, <75% reduction in seizure
      frequency (n = 32)], a strong positive association was found between higher SF-36
      scores (with the exception of physical functioning) and better seizure control.
      Health-related limitations in role performance differentiated best between the
      outcome categories. For patients with > or =75% reduction in seizure frequency,
      low seizure severity correlated with higher HRQOL ratings for scales measuring
      social function, vitality, and mental health. Depression levels (HAD scale
      scores) were on average low. Anxiety (HAD) increased significantly from A to D.
      CONCLUSIONS: HRQOL seems to be scored as a continuum in relation to seizure
      frequency. Seizure severity measures give complementary information.

PMID- 9579912
TI  - Ictal single photon emission computed tomography in occipital lobe seizures.
AB  - PURPOSE: Ictal single photon emission computed tomography (SPECT) has been
      evaluated as an adjunctive localizing technique in temporal lobe epilepsies and,
      to a lesser degree, in some extratemporal epilepsies. The purpose of this study
      was to determine whether occipital lobe seizures are associated with distinctive
      ictal cerebral blood perfusion (rCP) patterns. METHODS: SPECT was used with the
      tracer 99mTc HMPAO to image ictal rCP in 6 patients in whom clinical, EEG, and
      imaging data indicated occipital lobe seizures. RESULTS: Two patterns of rCP were
      seen. Four patients had hyperperfusion that was restricted to the occipital lobe,
      and two patients had hyperperfusion of the occipital lobe and the ipsilateral
      mesial temporal lobe, with hypoperfusion of the lateral temporal lobe. The latter
      2 patients had clinical and surface EEG evidence of temporal lobe involvement in
      the seizure discharge. CONCLUSIONS: Ictal rCP patterns in occipital lobe seizures
      are distinct from those in temporal lobe seizures and may vary according to
      whether or not ipsilateral temporal lobe structures are involved in the ictal
      discharge.

PMID- 9579913
TI  - Cavernous angioma presenting as pregnancy-related seizures.
AB  - PURPOSE: To determine the reason that one-quarter to one-third of epileptic women
      experienced an increased number of seizures during pregnancy. The cause of this
      increase is not always clearly understood and the principle emphasis of the
      literature is on the pregnancy-associated changes of anticonvulsant
      pharmacokinetics. METHODS: Two patients presented with recurrent seizures
      occurring only during pregnancy. Both had MRI findings typical of cavernous
      angiomas of the temporal lobe. RESULTS: In addition to changes in anticonvulsant
      pharmacokinetics, potential mechanisms underlying the exacerbation of seizures
      from a vascular malformation during pregnancy include effects of estrogen on
      temporal structures critically involved in epileptogenesis and changes within the
      malformation itself secondary to direct actions of estrogen and the hemodynamic
      changes of pregnancy. CONCLUSIONS: The possibility of an occult lesion such as
      cavernous angioma should be considered for seizures occurring during pregnancy.
      Even in the presence of a normal CT scan, an MRI investigation should be pursued,
      despite the ill-defined fears of MRI in pregnancy.

PMID- 9579914
TI  - Periictal Capgras syndrome after clustered ictal fear: depth-electroencephalogram
      study.
AB  - PURPOSE: To describe periictal Capgras syndrome as a result of rapid, successive
      bouts of ictal fear. METHODS: This periictal psychotic state was documented by
      depth EEG recordings. RESULTS: Episodes of paroxysmal fear, experienced as a
      vivid sensation of someone being nearby, corresponded with unilateral left limbic
      ictal discharge. CONCLUSIONS: Depersonalization, regardless of organic or
      functional origin, is an important contributor to the genesis of Capgras
      syndrome.

PMID- 9579915
TI  - Multiple kainic acid seizures in the immature and adult brain: ictal
      manifestations and long-term effects on learning and memory.
AB  - PURPOSE: While there is increasing evidence that the adverse effects of prolonged
      seizures are less pronounced in the immature than in the mature brain, there have
      been few investigations of the long-term effects of recurrent seizures during
      development. This study examined the effects of multiple administrations of the
      convulsant kainic acid (KA) on seizure characteristics and spatial learning as a
      function of brain development. METHODS: To determine the long-term effects of
      serial KA seizures during ontogeny, saline or convulsant doses of KA were given
      intraperitoneally 4 times, at 2-day intervals. Immature rats were given KA on
      P20, P22, P24 and P26; adult rats got KA on P60, P62, P64 and P66. Ictal
      characteristics and EEGs were recorded. To examine the effects of multiple KA
      seizures on the retention of spatial learning, water maze testing was performed
      before (immature group: from P16-19, adult group: from P56-P59) and after
      (immature: from P60-P63, adult: from P100-P103) KA injections. Finally, histology
      was performed to compare KA-induced damage at each age. RESULTS: In immature
      animals, serial KA administration resulted in seizures with a progressively
      longer onset latency and decreased severity. In contrast, KA serially
      administered to adult rats caused severe seizures after each of the 4 injections.
      In immature rats, epileptiform EEG changes were most prominent after the first KA
      injection, whereas in adults, prolonged paroxysmal EEG patterns were seen after
      all 4 KA injections. Before KA, both rat pups and adults acquired place learning
      in the water maze. One month after the final KA injection, there was no deficit
      in spatial learning retention in the immature group, whereas the adult group had
      profound impairment compared to age-matched, saline-injected controls. Histology
      revealed no lesions in immature rats treated multiple times with KA but profound
      cell loss in hippocampal fields CA4, CA3 and CA1 in rats treated serially with KA
      as adults. CONCLUSIONS: Previous studies have shown that a single KA injection
      causes prolonged status epilepticus (which persists for several hours), leading
      to severe histologic and behavioral sequelae in adult rats but not in pups. Our
      study extends those findings, demonstrating that immature rats are spared the
      cognitive and pathological sequelae of multiple injections of convulsant doses of
      KA as well.

PMID- 9579916
TI  - Anticonvulsant activity of felbamate in amygdala kindling model of temporal lobe
      epilepsy in rats.
AB  - PURPOSE: Previous studies have demonstrated that felbamate (FBM, 2-phenyl-1,3
      propanediol dicarbamate) at nontoxic doses exerts potent anticonvulsant activity
      in a variety of animal epilepsy or seizure models. We further characterized the
      anticonvulsant activity of FBM by using the kindling model of temporal lobe
      epilepsy (TLE). METHODS: The experiments were performed in fully kindled rats.
      The anticonvulsant effect of FBM was assessed by determining seizure severity,
      afterdischarge (AD) duration and seizure duration either at the focal seizure
      threshold, or after suprathreshold stimulation. In addition, the neurological
      performance of kindled rats after FBM administration was evaluated in the open
      field and by the rotorod test. RESULTS: FBM at doses of 12.5-50 mg/kg, given
      intraperitoneally (i.p.) 60 min before testing, dose-dependently increased the AD
      threshold (ADT). The maximal effect was achieved after the highest dose tested
      and reached almost 600% of the control ADT. This dose of FBM significantly
      diminished other seizure parameters, e.g., seizure severity, seizure duration,
      and AD duration. When the rats were stimulated with suprathreshold current (500
      microA) seizure severity was moderately but significantly reduced. No behavioral
      abnormalities were noted in kindled rats after administration of either of the
      doses. CONCLUSIONS: FBM potently increases the threshold for focal seizures and
      reduces seizure severity, seizure duration, and AD duration at doses that produce
      no adverse behavioral effects in amygdala-kindled rats. These data are thus
      compatible with clinical experience with FBM in TLE and substantiate that
      kindling is a good predictor of anticonvulsant activity against TLE.

PMID- 9579917
TI  - Periventricular nodular heterotopia: epileptogenic findings.
AB  - PURPOSE: We studied 17 patients with periventricular nodular heterotopia (PNH) to
      further investigate the electroclinical pictures and semiology of the associated
      seizures. METHODS: PNH was diagnosed by means of magnetic resonance imaging
      (MRI). The patients' clinical and familial histories were carefully analyzed, and
      their electroclinical features and course of epilepsy followed for periods
      ranging from 10 months to 22 years. The electroclinical data were compared with
      those of previously reported PNH cases. RESULTS: The patients were subdivided
      into those with bilateral (7) and unilateral (10) PNH. The former were mainly
      characterized by structural abnormalities in the posterior cerebral fossa and
      multiple seizure types; the latter were characterized by the paratrigonal
      location of the malformation and, frequently, by elementary seizures with a
      visual or auditory onset. Focal seizures were drug resistant in most cases. The
      interictal EEG abnormalities were always focal and consistent with the location
      of the PNH. A previously unreported photic driving of posterior background
      activity was observed in all patients and was always consistent with the PNH
      location. CONCLUSIONS: Our present findings and previously reported data show
      that bilateral and unilateral PNH cases are different in their morphological and
      electroclinical features and may be determined by different etiologies. The
      female predominance, frequent familial occurrence, and positive family history
      for epilepsy suggest that genetic factors may be involved in the genesis of
      bilateral and symmetrical PNH, whereas the presence of prenatal risk factors and
      its location in the watershed paratrigonal area suggest that vascular mechanisms
      may determine unilateral PNH.

PMID- 9579918
TI  - Altered seizure patterns after temporal lobectomy.
AB  - PURPOSE: We compared features of seizures occurring after temporal lobectomy with
      those of preoperative seizures in the same patients to determine whether aspects
      of postoperative partial seizures presage ultimate seizure control. METHODS:
      Seizure descriptions of 100 consecutive patients who underwent anterior temporal
      lobectomy (ATL) were obtained by our epileptologists before and after surgery.
      Follow-up for seizure control for all patients was obtained for a median of 5.5
      years. RESULTS: Twenty-six of the 100 patients had at least one diurnal complex
      partial seizure (CPS) after lobectomy. The proportion of patients with an aura
      for their CPS decreased from 86% preoperatively to 58% postoperatively. Fifty
      five percent had two or more aura features before surgery, as compared with 31%
      after lobectomy. Eleven of 18 (61%) with fewer than two postoperative aura
      features, as compared with 2 of 8 (25%) with two or more aura features ultimately
      had >90% seizure reduction postoperatively. Nineteen (95%) of 20 patients with
      only simple partial seizures (SPS) postoperatively ultimately obtained > or =90%
      reduction, and 7 (35%) of them became seizure-free. Although generalized tonic
      clonic seizures (GTCS) decreased from 70% to 39% after lobectomy, 7 (23%) of 30
      patients who had not had GTCS preoperatively had at least one after lobectomy,
      usually while receiving a lesser amount of antiepileptic drug (AED) therapy.
      Among the 27 patients with residual CPS, ultimate outcome was better among
      patients with removal of >6 cm as measured along the inferior temporal gyrus than
      among those with less extensive resections. CONCLUSIONS: In addition to
      eliminating or reducing the frequency of temporal lobe seizures, lobectomy may
      simplify or eliminate the aura features of residual CPS. The number of CPS aura
      features correlated inversely with ultimate postoperative seizure reduction.
      Ultimate seizure control among patients with only SPS was better than that of
      patients with CPS postoperatively. First-ever GTCS may occur when AED dosages are
      reduced after surgery.

PMID- 9579919
TI  - Seizure semiology of occipital lobe epilepsy in children.
AB  - PURPOSE: Occipital lobe epilepsy in children occurs as an idiopathic form, i.e.,
      Benign Epilepsy with Occipital Paroxysms (BEOP), and a symptomatic form. This
      study attempted to determine whether seizure semiology could distinguish between
      the two forms. METHODS: Fifty children (34 boys, 16 girls) with clinical seizures
      and interictal EEGs presenting occipital spikes were included consecutively in
      the study. Seizure onset was between the ages of 2 months and 15 years. Epilepsy
      was considered symptomatic when psychomotor retardation and/or abnormalities at
      neurological and/or neuroradiological examination were found: 17 children were
      classified as idiopathic, and the remaining 33 children were classified as
      symptomatic. Seizure semiology was assessed by means of a structured interview of
      the children and their parents, using a detailed questionnaire. Seizure semiology
      was determined to comprise motor (versive or other movements of the eyes, versive
      movements of the head, (hemiconvulsions), visual, other signs (e.g. vomiting and
      headache), and impairment of consciousness. RESULTS: There were no statistically
      significant differences in seizure semiology between the two groups. CONCLUSIONS:
      Seizure semiology cannot distinguish between different forms of occipital lobe
      epilepsy: Further clinical examination, clinical neurophysiological
      investigations, and neuroimaging studies are needed for a correct classification.

PMID- 9579920
TI  - Sensitivity of a seizure activity detection computer in childhood
      video/electroencephalographic monitoring.
AB  - PURPOSE: Few data describe the sensitivity of a "Seizure Activity Detection
      Computer" (SzAC) in childhood video/EEG (VEEG) monitoring, especially for very
      young children. We examined the accuracy of SzAC in childhood VEEG monitoring in
      different pediatric age groups. METHODS: We visually analyzed VEEG monitoring
      samples for randomly designated subsets of 56 patients with childhood epilepsy,
      reviewing 335 visually detected electrographic seizures to analyze the
      sensitivity of SzAC for each age group as well as the electrographic
      characteristics affecting the sensitivity of automated computer-based seizure
      detection. RESULTS: SzAC was positive in 227 of 335 (67.8%) visually identified
      electrographic seizures in the entire study group. The SzAC sensitivity for
      infants (age 2 months to 2 years) was 59.7% (43 of 72 seizures); for young
      children (age 3-10 years), sensitivity 56.5% (91 of 161 seizures). In adolescents
      (age 11-18 years), SzAC was positive in 93 of 102 (91.2%) seizures--i.e., in a
      significantly greater number of seizures than in younger age groups. SzAC was
      significantly less sensitive in detecting electrographic seizures characterized
      as being of short duration or of low voltage. CONCLUSIONS: The overall
      sensitivity of SzAC in detecting childhood electrographic seizures was 67.8%. The
      sensitivity was significantly less in younger age groups as compared with that in
      children aged >11 years. Electrographic seizures of relatively short duration or
      low voltage were often missed by SzAC.

PMID- 9579921
TI  - Identification of frontal lobe epileptic foci in children using positron emission
      tomography.
AB  - PURPOSE: Presurgical evaluation for intractable frontal lobe epilepsy (FLE) is
      difficult and invasive, partly because anatomic neuroimaging studies with
      computed tomography (CT) and magnetic resonance imaging (MRI) typically do not
      show a discrete lesion. In adult patients with FLE, functional neuroimaging of
      glucose metabolism with positron emission tomography (PET) is less sensitive in
      detecting focal metabolic abnormalities than in temporal lobe epilepsy (TLE).
      Comparable data on children with FLE are not available. METHODS: We used high
      resolution PET scanning of glucose metabolism to evaluate 13 children (age 17
      months to 17 years; mean age 9.5 years) with intractable FLE being considered for
      surgical treatment. Only children with normal CT and MRI scans were included.
      RESULTS: Hypometabolism including the frontal lobe was evident in 12 of the 13
      children, was unilateral in 11 of 13, and was restricted to the frontal lobe in 8
      of 13. One child showed bilateral frontal cortex hypometabolism and another had
      an ictal PET scan demonstrating unilateral frontal cortex hypermetabolism
      surrounded by hypometabolism. Additional hypometabolic areas outside the frontal
      cortex were observed in 5 children in parietal and/or temporal cortex.
      Localization of seizure onset on scalp EEG was available in 10 children and
      corresponded to the location of frontal lobe PET abnormality in 8. However, in 4
      of the 10 children, the extent of hypometabolism exceeded the epileptogenic
      region indicated by ictal EEG. In 2 of the 13 children, the abnormality evident
      on EEG was more extensive than that evident on PET. In the remaining 3 children
      for whom only interictal EEG data were available, the PET foci did not correspond
      in location to the interictal EEG abnormalities. In 11 of the 13 children, the
      presumed region of seizure onset in the frontal lobe, as based on analysis of
      seizure semiology, corresponded to the locations of frontal lobe glucose
      metabolism abnormalities. CONCLUSIONS: Although high-resolution PET appears to be
      very sensitive in localizing frontal lobe glucose metabolic abnormalities in
      children with intractable FLE and normal CT/MRI scans, the significance of
      extrafrontal metabolic disturbances requires further study; these may represent
      additional epileptogenic areas, effects of diaschisis, seizure propagation sites,
      or secondary epileptogenic foci.

PMID- 9579922
TI  - Asymmetries in the effect of side of seizure onset on recognition memory
      following intracarotid amobarbital injection.
AB  - PURPOSE: To assess interhemispheric differences in recognition memory for objects
      during the intracarotid amobarbital sodium procedure (IAP). METHODS: The
      recognition memory for real objects of patients with either right (RTLE; n = 28)
      or left (LTLE; n = 22) temporal lobe epilepsy was assessed at baseline, and after
      left and right intracarotid amobarbital sodium injection. RESULTS: There were no
      differences between groups on baseline performance. Performance following
      injection ipsilateral to the side of seizure focus was relatively lower for the
      LTLE as compared with the RTLE group, but this difference did not reach
      statistical significance. However, performance following injection contralateral
      to the side of seizure focus was significantly lower for the RTLE as compared
      with the LTLE group. Within-group differences in performance after ipsilateral as
      compared with contralateral injection were significant for the RTLE but not the
      LTLE group. The difference in interhemispheric asymmetry in IAP memory
      performance between RTLE and LTLE groups was reflected in decreased ability to
      classify LTLE patients as compared with RTLE patients about side of seizure
      onset, using a clinically applicable decision rule. CONCLUSIONS: Recognition
      memory during the IAP for real objects, simultaneously named and presented
      visually during encoding, is mediated effectively by both the left and right
      hemisphere when there is no seizure focus present. However, memory appears to be
      more vulnerable to the presence of a seizure focus in the right as compared with
      the left hemisphere.

PMID- 9579923
TI  - Vascular determinants of epilepsy: the Rotterdam Study.
AB  - PURPOSE: To investigate the relation between vascular determinants and epilepsy
      in an elderly population. METHODS: This is a cross-sectional, community-based,
      case-control study. The total study population was comprised of 4,944 subjects,
      65 of whom had epilepsy which conformed to International League Against Epilepsy
      (ILAE) criteria. Vascular determinants that were evaluated included a history of
      stroke or myocardial infarction, peripheral vascular disease, hypertension, serum
      total cholesterol and left ventricular hypertrophy. Multivariate logistic
      regression analysis was used to calculate prevalence odds ratios (OR), adjusted
      for age and gender, as a measure of the strength of the associations. RESULTS: A
      history of stroke was strongly associated with lifetime epilepsy (OR 3.3; 95% CI
      [Confidence Interval] 1.3-8.5), as well as with late-onset epilepsy (OR 3.1; 95%
      CI 0.9-10.6). All vascular determinants were associated with lifetime epilepsy
      and late-onset epilepsy, with odds ratios >1. When stroke patients were excluded,
      the odds ratios were statistically significant for the relationships between
      total cholesterol and late-onset epilepsy (OR 1.3, 95% CI 1.0-1.6) and left
      ventricular hypertrophy and late-onset epilepsy (OR 2.9, 95% CI 1.0-8.6).
      Furthermore, presence of any of these vascular indicators was twice as common
      among subjects with late-onset epilepsy as compared with subjects without
      epilepsy (OR 2.0, 95% CI 0.9-4.2), and this was statistically significant when
      stroke patients were excluded (OR 2.1, 95% CI 1.0-4.7). CONCLUSIONS: These
      results suggest that there may be a relationship between vascular factors and the
      risk of late-onset epilepsy, apart from the relationship that exists through
      clinically overt stroke.

PMID- 9579924
TI  - Relationship between seizure frequency and costs and quality of life of
      outpatients with partial epilepsy in France, Germany, and the United Kingdom.
AB  - PURPOSE: The relationship between seizure frequency and both health care costs
      and quality of life (QOL) was investigated in a retrospective, cross-sectional,
      multicenter study in France, Germany, and the United Kingdom. METHODS: Three
      hundred outpatients with stable partial epilepsy were approximately evenly
      distributed among five seizure-frequency groups, ranging from seizure-free in the
      last 3 months (group 1) to daily seizures (group 5). Economic data, obtained
      through patient interviews and record abstraction, comprised direct medical
      costs, direct nonmedical costs, and indirect costs for the preceding 3 months.
      Total societal costs in the three countries were pooled and converted to United
      States dollar equivalents. QOL was assessed through a self-administered
      questionnaire, the Functional Status Questionnaire (FSQ). RESULTS: Mean total
      costs increased from $780 in group 1 to $2,171 in group 5 (p = 0.0001), with
      significant increases in each cost category as seizure frequency increased.
      Greater seizure frequency also significantly (p = 0.0270) correlated with lower
      employment rates, which ranged from 57% in group 1 to 30% in group 5. QOL
      declined as seizure frequency increased. Particularly affected were basic and
      intermediate activities of daily living (ADL), mental health, social activity,
      and feeling about health. CONCLUSIONS: The study results show that higher seizure
      frequencies are associated with higher direct and indirect costs and with reduced
      QOL for patients with epilepsy.

PMID- 9579925
TI  - Disclose or conceal? Strategies of information management in persons with
      epilepsy.
AB  - PURPOSE: When handling information about their disease in their social contacts,
      persons with epilepsy try to avoid or limit stigmatization. We report two basic
      strategies of information management: general concealment and preventive
      disclosure. To test whether persons with epilepsy apply a strategy of preventive
      disclosure, we hypothesized that they would disclose their epilepsy when
      anticipating that their disease would make them conspicuous in social contacts
      and when believing that they would be able to forestall stigmatizing attribution
      processes through disclosure. METHODS: One hundred nineteen outpatients at the
      Bethel Epilepsy Center, Bielefeld, Germany, aged 16-74 years responded to a
      questionnaire assessing willingness to disclose their epilepsy in various
      fictitious daily scenarios, the perceived risk that the interaction partner might
      find out about their epilepsy (risk of detection), as well as the anticipated
      positive and negative social consequences of disclosure in these social
      situations. RESULTS: Willingness to disclose varied across the different
      scenarios, and only a few respondents rejected disclosure categorically.
      Willingness to disclose depended on the subjectively perceived risk of detection
      and the anticipated consequences of disclosure: Respondents were more willing to
      disclose their epilepsy the more they feared that their interaction partner would
      detect their disease or find out about it in another way and the more they
      anticipated that disclosure would enable them to exert a favorable impact on
      their partner's social judgment formation. CONCLUSIONS: Many persons with
      epilepsy appear to apply a strategy of preventive disclosure with which they
      strive to influence social judgment formation in their environment by
      purposefully disclosing their disease to forestall possible stigmatization
      processes.

PMID- 9579926
TI  - Development of hippocampal atrophy: a serial magnetic resonance imaging study in
      a patient who developed epilepsy after generalized status epilepticus.
AB  - PURPOSE: To investigate changes in hippocampal volume. METHODS: We used serial
      magnetic resonance imaging (MRI) in a patient who developed chronic epilepsy
      after having generalized tonic-clonic status epilepticus (SE). Five MRI
      investigations were performed during SE and a 58-month follow-up period.
      Hippocampal volumetric measurements and coregistration of scans were performed to
      detect hippocampal atrophy. RESULTS: During status both mesiotemporal regions
      returned a high signal on T2-weighted images. Two months after the onset of SE,
      bilateral hippocampal atrophy was detected. Further progressive hippocampal
      atrophy was detected in the subsequent 58 months by both hippocampal volumetric
      measurements and coregistration of scans. CONCLUSIONS: Our findings suggest that
      hippocampal atrophy is a process that may continue after the end of the SE.

PMID- 9579927
TI  - Failure of absorption of gabapentin after rectal administration.
AB  - PURPOSE: We wished to determine the extent of absorption of gabapentin (GBP)
      after rectal administration to children on maintenance therapy. METHODS: Two
      children scheduled for extensive surgery received GBP rectally and orally. A
      pharmacokinetic profile was derived after each route of administration. RESULTS:
      Serum GBP levels after rectal administration decreased at a rate similar to their
      rate of decrease after oral administration. However, GBP concentrations were much
      lower after rectal administration; therefore, we concluded that the aqueous
      solution was poorly absorbed rectally. The GBP half-life (t1/2) for the 2
      children after oral doses were 4.2 and 4.8 h. CONCLUSIONS: Rectal administration
      of GBP is not satisfactory when oral administration is interrupted. When oral GBP
      therapy is temporarily discontinued, clinicians should consider administration of
      alternative antiepileptic drugs (AEDs) that can be administered parenterally or
      rectally.

PMID- 9579928
TI  - Commission on European Affairs: appropriate standards of epilepsy care across
      Europe.ILEA.

PMID- 9579929
TI  - Myoclonus and epilepsy in childhood. Commission on Pediatric Epilepsy of the
      International League Against Epilepsy.

PMID- 9579930
TI  - Recommendations for neuroimaging of patients with epilepsy. Commission on
      Neuroimaging of the International League Against Epilepsy.

PMID- 9579931
TI  - Analysis of surgical blood loss and number of blood transfusions after temporal
      lobe resection performed in adults with epilepsy receiving valproate (VPA) in the
      immediate preoperative period.

PMID- 9579932
TI  - Teratogenic effects of antiepileptic drugs: what do we advise patients?

PMID- 9579934
TI  - Antiepileptic effects of tiagabine, a selective GABA uptake inhibitor, in the rat
      kindling model of temporal lobe epilepsy.
AB  - PURPOSE: We determined the antiepileptic profile of tiagabine (TGB), a selective
      gamma-aminobutyric acid (GABA) uptake inhibitor, in the rat kindling model of
      temporal lobe epilepsy (TLE). METHODS: The anticonvulsant and adverse effects of
      TGB were examined in amygdala- or hippocampal-kindled rats and compared with
      those of other GABA uptake inhibitors (SKF89976A and NNC-711) and conventional
      antiepileptic drugs [AEDs: valproate (VPA) and carbamazepine (CBZ)]. In addition,
      the antiepileptogenic effects of TGB on amygdala kindling development were
      examined. RESULTS: TGB (2.5-40 mg/kg intraperitoneally, i.p.) had potent and dose
      dependent anticonvulsant effects on both amygdala- and hippocampal-kindled
      seizures. The order of anticonvulsant potency of the three GABA uptake inhibitors
      tested was: NNC-711 > TGB > SKF-89976A and paralleled the in vitro GABA uptake
      efficacy. In addition, daily treatment with TGB 10 mg/kg for 10 days
      significantly retarded kindling development. Although adverse effects of TGB on
      motor systems were significantly less than those of VPA and CBZ, high toxic doses
      of TGB often caused EEG paroxysm and myoclonus. CONCLUSIONS: Our results indicate
      the clinical usefulness of TGB for treatment of drug-resistant TLE.

PMID- 9579933
TI  - Voltage-activated calcium channels: targets of antiepileptic drug therapy?
AB  - Voltage-gated calcium currents play important roles in controlling neuronal
      excitability. They also contribute to the epileptogenic discharge, including
      seizure maintenance and propagation. In the past decade, selective calcium
      channel blockers have been synthesized, aiding in the analysis of calcium channel
      subtypes by patch-clamp recordings. It is still a matter of debate whether
      whether any of the currently available antiepileptic drugs (AEDs) inhibit these
      conductances as part of their mechanism of action. We tested oxcarbazepine,
      lamotrigine, and felbamate and found that they consistently inhibited voltage
      activated calcium currents in cortical and striatal neurons at clinically
      relevant concentrations. Low micromolar concentrations of GP 47779 (the active
      metabolite of oxcarbazepine) and lamotrigine reduced calcium conductances
      involved in the regulation of transmitter release. In contrast, felbamate blocked
      nifedipine-sensitive conductances at concentrations significantly lower than
      those required to modify N-methyl-D-aspartate (NMDA) responses or sodium
      currents. Aside from contributing to AED efficacy, this mechanism of action may
      have profound implications for preventing fast-developing cellular damage related
      to ischemic and traumatic brain injuries. Moreover, the effects of AEDs on
      voltage-gated calcium signals may lead to new therapeutic strategies for the
      treatment of neurodegenerative disorders.

PMID- 9579935
TI  - Protective effect of zonisamide, an antiepileptic drug, against transient focal
      cerebral ischemia with middle cerebral artery occlusion-reperfusion in rats.
AB  - PURPOSE: The antiepileptic effects of zonisamide (ZNS) have been well documented
      experimentally and clinically. The purpose of this study was to examine whether
      ZNS reduces cerebral damage after transient focal ischemia in rats. METHODS:
      Ischemia was induced by a transient occlusion of the left middle cerebral artery
      (MCA) with a 3-0 nylon monofilament for 90 min. Neurological evaluation was
      performed by measuring the event of neurological deficit of the contralateral
      forepaw and hindpaw at 10 min and 1 day after MCA occlusion (MCAo). Brain infarct
      size was determined by measuring triphenyltetrazonium chloride-negative stained
      area of the serial brain sections 1 day after MCAo. RESULTS: The pre- or
      postischemic treatment with ZNS [(10-100 mg/kg p.o.), 30 min before and 4 h after
      or 15 min and 4 h after the occlusion] markedly reduced cerebral damage in the
      ipsilateral hemisphere and the neurological deficit induced by transient
      ischemia. The reducing effect on the damage was observed in the cortical and
      subcortical regions. Preischemic treatment with carbamazepine (CBZ 60 mg/kg p.o.
      twice 30 min before and 4 h after MCAo) tended to reduce the cerebral damage and
      neurological deficit, but the lower dose (20 mg/kg p.o. twice) did not. Valproate
      (VPA 1,000 mg/kg p.o. twice) also had no effect. CONCLUSIONS: ZNS at the
      anticonvulsant dose, unlike CBZ and VPA, ameliorated the brain infarction and the
      event of neurological deficit after transient focal cerebral ischemia. These data
      suggest that ZNS has therapeutic potential in protecting against ischemic
      cerebral damage, such as stroke.

PMID- 9579936
TI  - Maternal use of antiepileptic drugs and the risk of major congenital
      malformations: a joint European prospective study of human teratogenesis
      associated with maternal epilepsy.
AB  - PURPOSE: To quantify the risks of intrauterine antiepileptic drug (AED) exposure
      in monotherapy and polytherapy. METHODS: Data from five prospective European
      studies totaling 1,379 children were pooled and reanalyzed. Data were available
      for 1,221 children exposed to AED during pregnancy and for 158 children of
      unexposed control pregnancies. RESULTS: Overall, when comparing a subgroup of 192
      children exposed to AED with 158 children of matched nonepileptic controls, there
      was an increased risk of major congenital malformations (MCA) in children exposed
      to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI):
      1.2-4.7]. A significant increase in risk was found for children exposed to
      valproate (VPA) (RR 4.9; 95% CI: 1.6-15.0) or carbamazepine (CBZ) (RR 4.9; 95%
      CI: 1.3-18.0) in monotherapy. When comparing different AED regimens during all
      1,221 pregnancies, risks of MCA were significantly increased for the combination
      of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4-67.3) and the
      combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1-57.6). Offspring
      of mothers using > 1,000 mg VPA/day were at a significantly increased risk of
      MCA, especially neural tube defects, compared to offspring exposed < or =600 mg
      VPA/day (RR 6.8; 95% CI: 1.4-32.7). No difference in risk of MCA was found
      between the offspring exposed to 601-1,000 mg/day and < or =600 mg/day.
      CONCLUSIONS: This reanalysis shows that VPA is consistently associated with an
      increased risk of MCA in babies born to mothers with epilepsy. Significant
      associations were also observed with CBZ. Larger prospective population-based
      studies are needed to evaluate the risks of many other less frequently prescribed
      treatment regimens, including newly marketed AEDs.

PMID- 9579937
TI  - Dissociation in epilepsy and conversion nonepileptic seizures.
AB  - PURPOSE: We examined the dimensionality of the item content of the Dissociative
      Experiences Scale (DES) in relation to the clinical diagnosis of conversion
      nonepileptic seizures (C-NES) versus complex partial epilepsy (CPE). METHODS: The
      DES was administered to a sex- and age-matched sample of 132 patients with C-NES
      and 169 with CPE and was factor analyzed with principal components analysis (PCA)
      with varimax rotation. RESULTS: The mean total DES score was 15.1 in the C-NES
      group and 12.7 in the CPE group (p = 0.079). The factors obtained by PCA
      differentiated the CPE and C-NES groups more strongly than did the total DES
      score. The factor accounting for the most variance, interpreted as
      "depersonalization-derealization," was significantly greater in C-NES than CPE (p
      = 0.005). An "absorption-imaginative involvement" factor, which included some of
      the clinical features of posttraumatic stress disorder was elevated only in
      subjects reporting histories of childhood abuse (p = 0.001) regardless of the
      diagnosis of CPE or C-NES. An "amnestic" factor appearing to represent memory
      problems related to neurologic impairment showed a trend toward elevation in CPE
      (p = 0.056) and may have confounded the CPE versus C-NES distinction using total
      DES scores. CONCLUSIONS: The DES has separate underlying dimensions that appear
      to relate distinctively to depersonalization and derealization, childhood trauma,
      and neurologic impairment. The heterogeneous item content of the DES is a
      potential confound that should be appreciated when this instrument is used to
      study dissociation in neuropsychiatric populations.

PMID- 9579938
TI  - The relation between quantitative MRI measures of hippocampal structure and the
      intracarotid amobarbital test.
AB  - PURPOSE: The increasing sophistication of quantitative magnetic resonance imaging
      (MRI) techniques has generated hopes that they may eventually supersede the
      intracarotid amobarbital procedure (IAP) in the presurgical screening for
      bilateral abnormalities in prospective candidates for temporal lobe epilepsy
      surgery. As the first step toward this aim, the purpose of this study was to
      examine the relationship between these measures of structural and functional
      integrity. METHODS: We examined the relation between memory performance and
      pass/fail rates on the IAP and two MRI measures of hippocampal integrity:
      hippocampal volumes, adjusted for intracranial volume (HCvol) and hippocampal T2
      relaxometry (HCT2), in 48 patients with medically intractable temporal lobe
      epilepsy, who underwent the IAP as part of their presurgical evaluation for
      temporal lobectomy. RESULTS: The unilateral memory scores from the IAP were not
      significantly correlated with the corresponding HCvol or HCT2 measures in the
      right- and left-temporal-lobe groups. However, the MRI measures of hippocampal
      asymmetry (right minus left HCvol, right minus left HCT2) were significantly
      correlated with our measure of functional asymmetry, the right minus left
      hemisphere memory score from the IAP, supporting the role of the IAP in
      lateralising temporal lobe dysfunction. Forty-six patients with unilateral
      hippocampal sclerosis and concordant EEG studies passed the IAP. Two patients
      failed the memory component of the IAP. In both cases, other presurgical
      investigations suggested bilateral abnormalities. CONCLUSIONS: We conclude that
      patients with unilateral hippocampal sclerosis, established by a rigorous
      quantitative MRI protocol, and concordant ictal and interictal EEG findings may
      not be at risk for postoperative amnesia, despite baseline neuropsychological
      deficits suggestive of bilateral disturbance.

PMID- 9579939
TI  - Widespread cerebral structural changes in two patients with gelastic seizures and
      hypothalamic hamartomata.
AB  - PURPOSE: We tested the hypothesis that widespread extralesional abnormalities of
      cerebral structure exist in association with apparently isolated hypothalamic
      hamartomata, providing a structural basis for the poor response of seizures to
      removal of the hamartoma or other apparently focal epileptogenic zones present.
      METHODS: High-resolution magnetic resonance imaging (MRI) brain scans of 2
      patients with hypothalamic hamartomata were quantified by determination of
      regional distribution and symmetry of distribution of cortical gray matter and
      subcortical matter volumes. The results were compared with normal ranges for the
      distribution of such tissues in 33 controls. RESULTS: Both patients had
      abnormalities of distribution of gray and subcortical matter, whereas control
      subjects did not. These abnormalities were beyond the hamartoma itself, in areas
      of cerebrum that on visual inspection alone appeared completely normal.
      CONCLUSIONS: Extralesional abnormalities of cerebral structure are present in the
      cerebrum of patients with hypothalamic hamartoma, as in most patients with other
      dysgeneses. These abnormalities may explain the poor outcome of epilepsy surgery
      in patients with this form of dysgenesis. These preliminary findings require
      further investigation.

PMID- 9579940
TI  - Changes in regional cerebral blood flow beyond the temporal lobe in unilateral
      temporal lobe epilepsy.
AB  - PURPOSE: Single photon emission computed tomography (SPECT) is widely used to
      evaluate functional abnormalities during the epileptic event. Changes in regional
      cerebral blood flow (rCBF) are well defined in patients with temporal lobe
      epilepsy (TLE) undergoing surgical resection. Nonetheless, the interpretation of
      ictal abnormalities in CBF beyond the temporal lobes has not been carefully
      addressed. METHODS: We assessed 4 patients with pathologically proven unilateral
      TLE who had significant ipsilateral frontal hypoperfusion in ictal studies with
      no other abnormalities but chronic epilepsy accounting for such findings.
      Patients were assessed as candidates for surgery by interictal EEG,
      neuropsychological studies, brain magnetic resonance imaging, scalp electrode
      video-EEG monitoring, and ictal SPECT. RESULTS: Characteristic hyperperfusion was
      evident over the temporal lobe ipsilateral to the EEG focus, with significant
      hypoperfusion over the frontal region in 3 patients. In patient 4, frontal
      hypoperfusion was not statistically significant. CONCLUSIONS: SPECT demonstrated
      relative rCBF changes beyond the epileptogenic zone in unilateral TLE. Our
      findings provide further insight into the pathophysiological changes underlying
      this condition.

PMID- 9579941
TI  - Cyclic alternating pattern as a provocative factor in nocturnal paroxysmal
      dystonia.
AB  - PURPOSE: We made a polygraphic study of 6 patients with nocturnal paroxysmal
      dystonia (NPD) in which the cyclic alternating pattern (CAP) parameters were
      compared with those of a group of age- and sex-matched controls. METHODS: All
      patients met the requirements for NPD diagnosis, characterized by generalized
      stereotyped movements (dystonic-dyskinetic), with a 1-min centered duration but
      with no clear evidence of epileptic abnormalities in the waking EEG and during
      nocturnal recordings. RESULTS: Besides the major events, the NPD polysomnograms
      also showed shorter, repeated episodes of shorter duration (generally <20 s)
      consisting of abrupt movements involving one or more body segments. Overall, the
      motor events in patients with NPD were closely related to periods of unstable non
      REM (NREM) sleep, as evidenced by the sequences of CAP, and began during an A
      phase. According to the conventional scoring parameters, NPD and controls
      differed only in sleep latency (+14 min in the NPD patients: p < 0.04). However,
      the architecture of sleep in the group with NPD was characterized by prolonged
      and irregular NREM/REM cycles. In addition, the NPD recordings showed
      significantly higher values of CAP rate (p < 0.0001). When major motor attacks
      were suppressed by medication, sleep was characterized by a decrease in the
      excessive amounts of CAP rate and by a more regular architecture. CONCLUSIONS:
      The modulatory role of CAP on nocturnal motor events is reported.

PMID- 9579942
TI  - Initial human experience with ganaxolone, a neuroactive steroid with
      antiepileptic activity.
AB  - PURPOSE: Studies were conducted to establish the safety, tolerability, and
      pharmacokinetics of the antiepileptic drug (AED) ganaxolone. Ganaxolone belongs
      to a novel class of neuroactive steroids called epalons, which specifically
      modulate the gamma-aminobutyric acid type A (GABA[A]) receptor in the central
      nervous system (CNS). Chemically related to progesterone but devoid of any
      hormonal activity, the epalons have potent antiepileptic, anxiolytic, sedative,
      and hypnotic activities in animals. METHODS: Ninety-six healthy male and female
      volunteers received ganaxolone in a variety of formulations, doses, and dosing
      regimens. The pharmacokinetics of ganaxolone were systematically characterized,
      and adverse events associated with drug use were documented. RESULTS: Ganaxolone
      was well tolerated after single doses (< or =1,500 mg) and after multiple doses
      (< or =300 mg b.i.d. for 10 days). Steady-state plasma levels (trough) occurred
      after approximately 7 days of dosing, with mean steady-state plasma
      concentrations (Cmax) in multiple dose studies of between 32 ng/ml (50-mg doses)
      and 376 ng/ml (500-mg doses). No serious or life-threatening adverse events
      attributed to the drug were observed. The majority of adverse events reported
      were mild (82%) to moderate (14%) and were limited to headache, dizziness,
      somnolence, gastrointestinal disturbances, and malaise. CONCLUSIONS: Ganaxolone
      alone or formulated with pharmaceutical-grade excipients is rapidly absorbed from
      the gastrointestinal tract after oral administration in doses ranging from 50 to
      1,500 mg. Pharmacokinetic analysis revealed a linear and proportional increase in
      the area under the curve (AUC) and Cmax values with increasing dose within the
      expected therapeutic dose range. Safety and tolerability in the clinical program
      were unremarkable.

PMID- 9579943
TI  - Migraine with visual aura and photosensitive epileptic seizures.
AB  - A relationship between epilepsy and migraine has long been postulated, but the
      nature of this interaction is still debated. We observed this association in a 23
      year old man with a history of migraine with visual aura who had seizures at age
      15 years while watching television. Waking EEG was normal, but sleep recordings
      demonstrated posterior spike-waves during sleep. During intermittent photic
      stimulation (IPS), a photoparoxysmal response occurred, maximum in occipital
      areas. Brain magnetic resonance imaging scan was normal. Seizures did not recur
      after 4-year treatment with valproate. He is currently seizure-free, but
      continues to have rare migraine with visual aura. The role of spreading
      depression or of a putative dopaminergic failure in occipital cortex is
      discussed.

PMID- 9579944
TI  - Zonisamide monotherapy in newly diagnosed infantile spasms.
AB  - PURPOSE: We determined the short-term efficacy of zonisamide (ZNS) monotherapy in
      newly diagnosed patients with infantile spasms (IS). METHODS: Eleven hospitals
      participated in this open, prospective trial. ZNS 3-10 mg/kg/day was administered
      as the second-choice drug to 11 newly diagnosed patients with IS (cryptogenic 3,
      symptomatic 8) who failed to respond to high-dose vitamin B6. RESULTS: Four
      infants with symptomatic IS had cessation of spasms and disappearance of the
      hypsarrhythmia. In these responders, the spasms ceased after a few days (1-5
      days) of treatment at a dose of ZNS 4-5 mg/kg/day which produced plasma ZNS
      concentrations ranging from 5.2 to 16.3 microg/ml (mean 9.8 microg/ml). There
      were two relapses (50%) 4-6 weeks after cessation of seizures, however. Relapse
      was predicted by effects of ZNS on EEG; the 2 infants in whom an abnormal EEG
      persisted had relapses, whereas the 2 whose EEG normalized remained seizure-free
      (follow-up 20 and 26 months). No adverse reactions were noted. CONCLUSIONS: ZNS
      may be effective in the initial treatment of selected patients with IS.

PMID- 9579945
TI  - Lamotrigine in pregnancy and lactation: a case report.
AB  - PURPOSE: We investigated the effect of pregnancy on the kinetics of lamotrigine
      (LTG), passage of LTG over the placenta and the excretion of the drug in breast
      milk. METHODS: We used high-performance liquid chromatography to determine
      concentrations of LTG in plasma and in breast milk in a woman who was treated
      with LTG monotherapy during pregnancy and lactation. RESULTS: Plasma levels of
      LTG decreased as pregnancy progressed. The ratio of dose to plasma concentration
      was 5.8 times higher at delivery and 3.6 times higher in late pregnancy as
      compared with 5 months postpartum, suggesting enhanced clearance of LTG during
      pregnancy. The concentration ratio of umbilical cord to mother's plasma was 1.2
      indicating extensive passage of LTG over the placenta. The LTG plasma
      concentration in the newborn was still 48 h after birth similar to the plasma
      levels of the mother at delivery and in the umbilical cord. The ratio of milk to
      plasma concentration was 0.6 2 weeks after delivery and the plasma concentration
      in the breast-fed child was 25% of the mother's plasma levels. No adverse effects
      were observed in the newborn. CONCLUSIONS: The kinetics of LTG may be influenced
      by pregnancy to such a degree that dose adjustments may be indicated. Due to an
      extensive passage of LTG into breast milk, and a slow elimination in the newborn,
      LTG concentrations in the nursed infant may reach levels at which pharmacological
      effects can be expected.

PMID- 9579946
TI  - Olfactory prodromal symptoms and unilateral olfactory dysfunction are associated
      in patients with right mesial temporal lobe epilepsy.
AB  - PURPOSE: We report a patient with mesial temporal lobe epilepsy (MTLE) with
      olfactory prodromal symptoms manifested as an unpleasant smell of onions, who was
      found to have an ipsilateral deficit of olfactory naming (olfactory agnosia).
      METHODS AND RESULTS: Preoperative olfactory testing revealed a selective right
      sided olfactory deficit for naming of odors. Olfactory threshold was within the
      normal range. The patient has been seizure free after selective
      amygdalohippocampectomy for 4 months. No olfactory prodromal events have occurred
      since surgery. Olfactory testing 3 months after resection showed that right-sided
      odor naming was still impaired. CONCLUSIONS: We conclude that olfactory prodromal
      symptoms may be associated with unilateral olfactory dysfunction, and
      lateralization of seizure origin may be possible by unilateral olfactory testing.

PMID- 9579947
TI  - Intraventricular interferon-alpha stops seizures in Rasmussen's encephalitis: a
      case report.
AB  - A 3.5-year-old girl had epilepsia partialis continua of the right side. Clinical
      and laboratory findings were consistent with Rasmussen's encephalitis. Treatment
      with high-dose methylprednisolone led to temporary control of seizures, but for 2
      years, the seizures remained refractory to phenobarbital, phenytoin, lorazepam,
      carbamazepine, valproic acid, vigabatrin, gabapentin, and lamotrigine. A 6-week
      course, and later a 6-month course, of intraventricular interferon-alpha almost
      totally suppressed the seizures. Although moderately hemiparetic, the child has
      reasonable neurologic function with mild speech delay. She is receiving her third
      course of treatment, and seizures remain completely controlled.

PMID- 9579948
TI  - Special report from the World Federation of Neurology. The worldwide impact of
      new drugs: development, distribution, and use.
AB  - Access to appropriate drug treatments and preventive agents for neurologic
      disorders is determined by medical, economic, political, social, and personal
      choices and policies. The development of new agents is dominated by large, often
      transnational companies located in economically advanced countries. Adequate
      breadth and stability of pharmaceutical supplies may be jeopardized by local
      economic, physical, and organizational constraints. Appropriate medical choices
      of drugs, their number, routes of administration, and sources, are made by
      physicians informed by their basic and continuing medical education but also
      influenced to varying degrees by patient expectation, financial incentives, and
      marketing information provided by the drug industry. Attempts to increase the
      availability of necessary drug treatment for all include initiatives by the World
      Health Organization, attention of national health planners to drug development,
      supply, and use, and industry-government cooperation. Although there are
      significant differences among countries, many national health planners have taken
      similar approaches: increasing attention to cost-effectiveness in prescribing and
      to competitive purchasing; the use of essential drug lists, formularies, and
      generic drugs; the devising of economic incentives for the development of needed
      but unprofitable drugs; careful planning of drug procurement and storage; and an
      emphasis on professional and patient education.

PMID- 9579949
TI  - ILAE Commission report. Restrictions for children with epilepsy. Commission of
      Pediatrics of the ILAE. International League Against Epilepsy.

PMID- 9579950
TI  - Mortality in epilepsy.

PMID- 9579951
TI  - Cause-specific mortality in epilepsy: a cohort study of more than 9,000 patients
      once hospitalized for epilepsy.
AB  - PURPOSE: We studied overall and cause-specific mortality rates in a large cohort
      of patients with epilepsy compared with mortality rates of the general population
      in the same geographic area. METHODS: The cohort consisted of all patients (N =
      9,061) aged > 15 years admitted with a diagnosis of epilepsy for inpatient care
      in Stockholm during the years 1980-1989. All patients were followed in the
      National Cause-of-Death Register, from which the causes of death were obtained,
      until December 31, 1992. Thus, 53,520 person-years were observed. Mortality rates
      were compared with those of the general population of Stockholm. RESULTS: We
      observed 4,001 deaths in the cohort, compared with an expected number of 1,109
      deaths in the general population. This yielded a standardized mortality ratio
      (SMR) of 3.6 [95% confidence interval (CI) 3.5-3.7]. Although highest in the
      younger patients, the SMR was significantly increased in all age groups. The
      excess mortality rate in the cohort was due to a wide range of causes of death,
      including malignant neoplasms [SMR 2.6 (2.4-2.8)], diseases of the circulatory
      system, [SMR 3.1 (3.0-3.3)], diseases of the respiratory system [SMR 4.0 (3.6
      4.5)], diseases of the digestive system [SMR 5.1 (4.4-5.8)], and injuries and
      poisoning [SMR 5.6 (5.0-6.3)]. CONCLUSIONS: Our results demonstrate that this
      large subgroup of patients with a diagnosis of epilepsy, once hospitalized and
      discharged, is a population at risk, with an excess mortality rate due to several
      different causes.

PMID- 9579952
TI  - Epilepsy in Pakistan: stigma and psychosocial problems. A population-based
      epidemiologic study.
AB  - PURPOSE: To assess the stigmatization and psychosocial problems of persons with
      epilepsy in Pakistan. METHODS: A population-based, cross-sectional epidemiologic
      study of 241 persons with epilepsy identified from an at-risk population of
      24,130 individuals (64.7% from urban and 35.3% from rural areas). Of these
      patients, 77% suffered from recurrent non-febrile generalized convulsions. We
      evaluated degree of stigmatizations (i.e., avoidance by friends, neighbors, and
      others), and the effect of epilepsy on other psychosocial aspects (e.g.,
      marriage), and also the relationships between gender and level of education of
      the patients, and stigmatization. RESULTS: Patients with epilepsy in Pakistan do
      not appear to be highly stigmatized, but their education and grades are affected
      by the disorder. They have difficulty performing activities of daily living and
      find it hard to make decisions about whether to marry or to have children. Women
      believed that they were more dangerous to others, received less help from their
      families, and, more frequently than men, encouraged others to avoid them. Women
      were also more likely than men to express the belief that people with epilepsy
      should not marry, but in fact, women more frequently married as compared men-a
      fact influenced by social and cultural pressures, including pressure from family,
      because it is nearly always the responsibility of the parents to arrange the
      marriage of a daughter. Influence of education indicates that people with
      epilepsy who have higher education, as compared with those with less education,
      had fewer children, were less often avoided by their classmates and neighbors,
      had fewer problems with plans for education, less frequently encouraged others to
      avoid them, were more frequently married, and believed that they were more
      dangerous to others. Most people believed that their conditions had a physical
      basis; only 3.1% attributed their epilepsy to supernatural causes. CONCLUSIONS:
      Stigmatization regarding epilepsy has not been proven to be an important feature
      in the culture of Pakistan because none of the observations are statistically
      significant as per P-value.

PMID- 9579953
TI  - Sexual function in women with epilepsy.
AB  - PURPOSE: To examine certain aspects of sexual behaviour and attitudes in a group
      of women with epilepsy using a validated questionnaire (Sexuality Experience
      Scales), and effects of antiepileptic drugs (AEDs) on sex hormone binding
      globulin (SHBG), total testosterone (TT), and free testosterone (FT). METHODS:
      One hundred ninety-five women all attending a hospital-based epilepsy clinic were
      recruited. One hundred fifty-nine received AED therapy and 36 women did not. A
      control group of 48 women was also recruited. All women completed the first two
      Sexuality Experience Scales (SES 1 and SES 2), and those women in stable
      heterosexual relationships completed SES 3 and SES 4. At the same time blood was
      taken for TT and SHBG levels. FT was calculated using the method of Nanjee and
      Wheeler (22). RESULTS: Women receiving AED therapy achieved significantly higher
      SES 1 and SES 2 scores than the rest of the women, suggesting that they adhered
      to a stricter sexual morality and were less open to psychosexual stimulation than
      the rest of the women treated. Women in the treated group were less likely to
      have received further education than the controls, a factor that influences SES 1
      and SES 2 scores. There were no significant differences between the three groups
      on SES 3 or SES 4, with the exception of the orgasmic adequacy (OE) scale of SES
      3 where those women in the treated group attained a higher mean score than the
      controls, suggesting that they found orgasm less satisfying. Women receiving AEDs
      had significantly higher SHBG and TT than controls and untreated patients. There
      were no differences in FT between the groups. Those women receiving AEDs also
      exhibited the expected midcycle rise in FT. There was no significant correlation
      between FT and the desired frequency of intercourse or enjoyment of it for the
      three groups. CONCLUSIONS: Women in the treated group appeared to be more "moral"
      and less open to sexual approach, but those who had regular partners appeared to
      desire and enjoy intercourse as much as the control and untreated groups. This
      could be explained by differences in demographic characteristics of the study
      groups or be indicative of a bimodal distribution of sexual interest in these
      women. As FT was within physiological norms for each study group this cannot be
      cited as a cause for hyposexuality.

PMID- 9579954
TI  - Three patterns of catamenial epilepsy.
AB  - PURPOSE: On the basis of the neuroactive properties of estradiol and progesterone
      and the menstrually related cyclic variations of their serum concentrations, we
      propose the existence of three hormonally based patterns of seizure exacerbation.
      Because previous reports both support and refute the concept of catamenial
      epilepsy, we test the hypothesis by charting seizures and menses and measuring
      midluteal serum progesterone levels to estimate the frequency of epileptic women
      with catamenial seizure exacerbation. METHODS: One hundred eighty-four women with
      intractable complex partial seizures (CPS) charted their seizure occurrence and
      onset of menstruation on a calendar for one cycle during which they had a
      midluteal blood sample taken for serum progesterone determination on day 22.
      Levels >5 ng/ml were considered ovulatory. The cycle was divided into four phases
      with onset of menstruation being day 1: menstrual (M) = -3 to +3, follicular (F)
      = 4 to 9, ovulatory (O) = 10 to -13, and luteal (L) = -12 to -4. Average daily
      seizure frequency for each phase was calculated and compared among phases by
      repeated-measures analysis of variance (ANOVA) and the Student-Newman-Keul's
      test, separately for ovulatory and anovulatory cycles. RESULTS: The 1,324
      seizures recorded during 98 ovulatory cycles occurred with significantly greater
      (p < 0.001) average daily frequency during the M (0.59) and O (0.50) phases than
      during the F (0.41) and L (0.40) phases, offering support for perimenstrual
      (catamenial 1) and preovulatory (catamenial 2) patterns of seizure exacerbation.
      The 1,523 seizures recorded during 86 anovulatory cycles occurred with
      significantly lower (p < 0.001) average daily frequency during the F phase (0.49)
      than during all other phases (M = 0.78, O = 0.74, L = 0.74), offering support for
      seizure exacerbation throughout the second half of inadequate luteal phase cycles
      (catamenial pattern 3). Although 71.4% of the women with ovulatory cycles and
      77.9% with inadequate luteal phase cycles had seizure exacerbation in relation to
      one of the three patterns of catamenial epilepsy, approximately one third of the
      women showed at least a twofold increase in average daily seizure frequency. We
      propose a twofold or greater increase as a reasonable definition of catamenial
      epilepsy. CONCLUSIONS: Charting of seizures and menses and determination of day
      22 progesterone levels during each cycle may be sufficient to establish the
      existence of three distinct patterns of catamenial epilepsy. Approximately one
      third of women with intractable CPS may have catamenial epilepsy.

PMID- 9579955
TI  - Central benzodiazepine/gamma-aminobutyric acid A receptors in idiopathic
      generalized epilepsy: an [11C]flumazenil positron emission tomography study.
AB  - PURPOSE: Previous [11C]flumazenil (FMZ) positron emission tomography (PET)
      investigations in patients with idiopathic generalized epilepsy (IGE) have
      demonstrated nonsignificant global cortical decreases in central benzodiazepine
      gamma-aminobutyric acid A (GABA[A]) receptor (cBZR) binding or focal decreases in
      the thalamus and increases in the cerebellar nuclei with no changes in cerebral
      cortex. We previously reported lower [11C]FMZ binding in cerebral cortex of IGE
      patients treated with valproate (VPA) than in cerebral cortex of controls. We now
      report high-resolution three-dimensional [11C]FMZ PET studies in a larger number
      of subjects using an improved method to detect differences in cBZR between IGE
      patients and controls and a more powerful longitudinal design to determine the
      functional effect of VPA. METHODS: We compared parametric images of [11C]FMZ
      volume of distribution (FMZVD) in 10 IGE patients before and after addition of
      VPA and in 20 normal subjects. RESULTS: Mean FMZVD was significantly higher in
      the cerebral cortex (11%, p = 0.009), thalamus (14%, p = 0.018), and cerebellum
      (15%, p = 0.027) of the 10 IGE patients as compared with that of 20 normal
      controls. Using statistical parametric mapping, no significant areas of focal
      abnormality of FMZVD were detected. Addition of VPA was not associated with a
      significant change in mean FMZVD in any brain area. CONCLUSIONS: Our finding of
      increased FMZVD in IGE could reflect microdysgenesis or a state of cortical
      hyperexcitability. Our data suggest that short-term VPA therapy does not affect
      the number of available cBZR in patients with IGE.

PMID- 9579956
TI  - What is the relationship between arachnoid cysts and seizure foci?
AB  - PURPOSE: Arachnoid cysts are sometimes encountered in MRIs performed for a
      variety of reasons. In patients with epilepsy, particularly those with refractory
      epilepsy, arachnoid cysts are often assumed to be related to their seizure focus.
      We conducted a study to investigate this putative relationship. METHODS: A
      retrospective study on the incidence of arachnoid cysts was performed in patients
      seen in our Epilepsy Clinic who had CT or MRI scans, interictal EEGs or ictal
      EEGS. Locations of seizure foci in these patients were defined from clinical and
      electrophysiologic data. RESULTS: Seventeen of 867 patients had arachnoid cysts.
      Twelve patients had temporal lobe cysts and only 3 of them had temporal lobe
      seizures. Four patients had frontal lobe cysts and only 1 had frontal lobe
      seizures ipsilateral to the cyst. One patient had a cerebello-pontine angle cyst
      and frontal lobe seizures. Thus, clinical manifestations of seizures and EEG
      findings (interictal and/or ictal) indicated that the seizure focus was adjacent
      to the cysts in only 4 patients (23.5%). CONCLUSIONS: Our findings suggest that
      arachnoid cysts are often an incidental finding in patients with epilepsy and do
      not necessarily reflect the location of the seizure focus.

PMID- 9579957
TI  - Age at onset and neuropsychological function in frontal lobe epilepsy.
AB  - PURPOSE: Previous studies into the cognitive consequences of frontal lobe
      epileptic dysfunction may have proved inconclusive, due to a factor not commonly
      accounted for: Damage or disturbance during different epochs of development may
      give rise to different levels of neuropsychological dysfunction. In this study,
      we investigated the influence of age at onset on cognitive performance in a group
      of subjects with frontal lobe epilepsy (FLE). METHODS: Seventy-four subjects (42
      with left, and 32 with right) FLE were classified into early (0-6 years),
      intermediate (7-11 years) or late onset (> or =12 years) and their performance
      recorded on a battery of measures assessing both executive and motor skills.
      RESULTS: On the measures of executive functioning, no consistent pattern emerged,
      whereas on the measures of motor skill, the results suggested that a right-sided
      early onset (i.e., 0-6 years) did not impair performance compared to a later
      lesion within the same hemisphere. Furthermore, this sparing of performance was
      not observed within the left hemisphere. CONCLUSIONS: Overall, the results
      suggest that individuals with differing ages of epilepsy onset will be
      differentially impaired on certain cognitive tasks. Several tentative
      ramifications of these results are suggested.

PMID- 9579958
TI  - Continuous source imaging of scalp ictal rhythms in temporal lobe epilepsy.
AB  - PURPOSE: We wished to determine whether continuous EEG source imaging can predict
      the location of seizure onset with sublobar accuracy in temporal lobe epilepsy
      (TLE). METHODS: We retrospectively analyzed the earliest scalp ictal rhythms,
      recorded with 23- to 27-channel EEG, in 40 patients with intractable TLE. A
      continuous source analysis technique with multiple fixed dipoles (Focus 1.1)
      decomposed the EEG into source components representing the activity of major
      cortical sublobar surfaces. For the temporal lobe, these were basal, anterior
      tip, anterolateral, and posterolateral cortex. Ictal EEG onset was categorized
      according to its most prominent and leading source component. All patients
      underwent intracranial EEG studies before epilepsy surgery, and all had a
      successful surgical outcome (follow-up >1 year). RESULTS: Most patients with
      ictal rhythms having a predominant basal source component had hippocampal-onset
      seizures, whereas those with seizures with prominent lateral source activity had
      predominantly temporal neocortical seizure origins. Seizures with a prominent
      anterior temporal tip source component mostly had onset in entorhinal cortex.
      Seizures in some patients had several equally large and nearly synchronous source
      components. These seizures, which could be modeled equally well by a single
      oblique dipole, had onset predominantly in either entorhinal or lateral temporal
      cortex. CONCLUSIONS: Multiple fixed dipole analysis of scalp EEG can provide
      information about the origin of temporal lobe seizures that is useful in
      presurgical planning. In particular, it can reliably distinguish seizures of
      mesial temporal origin from those of lateral temporal origin.

PMID- 9579959
TI  - The effect of television frame rate on EEG abnormalities in photosensitive and
      pattern-sensitive epilepsy.
AB  - PURPOSE: Seizures provoked by television viewing may be triggered by patterns in
      the television image or by flicker from the display itself. We examined the
      incidence of EEG abnormalities elicited by patterns displayed on television sets
      with two different frame rates to evaluate the likely contribution of
      photosensitive and pattern-sensitive mechanisms to television- and video-game
      epilepsy. METHODS: Televisions with frame rates of 50 and 100 Hz were used to
      present 35 patients who were photosensitive or pattern-sensitive with grating
      patterns. These patterns comprised vertical square-wave and sine-wave gratings of
      90% contrast, and the spatial frequency was varied between 0.25-7 cycles/degree.
      EEGs were analysed for laboratory sensitivity to patterned and unpatterned
      intermittent photic stimulation (IPS). RESULTS: Significantly fewer EEG
      abnormalities were elicited by patterns displayed on the 100 Hz frame-rate
      television than on the 50-Hz frame-rate television. No abnormalities were
      observed in response to the blank screens of either television. Thirty-three
      patients showed abnormalities in response to patterned IPS but only 15 in
      response to diffuse flash. Two patients showed no laboratory evidence of
      photosensitivity. Patients who were sensitive to patterned IPS at 50 Hz were
      significantly more likely to demonstrate abnormalities to patterns displayed on
      the 100-Hz frame-rate television than were patients who were not sensitive to 50
      Hz patterned IPS. CONCLUSIONS: We suggest that for many patients, the combination
      of high-contrast patterns and screen flicker may elicit the observed EEG
      abnormalities. For patients with sensitivity to screen flicker, the use of a high
      frame-rate television may be beneficial in reducing the risk of seizures.

PMID- 9579960
TI  - Significance of spikes recorded on intraoperative electrocorticography in
      patients with brain tumor and epilepsy.
AB  - PURPOSE: Patients with medically intractable epilepsy due to brain tumors may
      undergo resective surgery for treatment of both the tumor and the epilepsy. In
      this instance, the extent of surgical resection is sometimes guided by spikes
      recorded on intraoperative electrocorticography (ECoG). Whether spikes recorded
      by electrocorticography imply active epileptogenicity has not been addressed
      adequately. METHODS: We performed preresection and postresection
      electrocorticography on 36 patients with brain tumor and seizures. There were 31
      low-grade gliomas, 4 high grade gliomas, and 1 dysembryonic neuroepithelial
      tumor. Patients had resection of the tumor to normal tissue margins only. No
      additional surgery was performed, based on electrocorticography findings.
      Patients were divided into 2 groups: Group I (no seizures or rare seizures after
      resection) and Group II (recurrent seizures). Recorded spikes were analyzed for
      spike distribution and spike discharge rate. RESULTS: On preresection ECoG, 85%
      of patients in Group I and 88% of patients in Group II had spikes. In Group I,
      70% of patients had spikes over the tumor bed, and 63% of patients had spikes in
      the surrounding tissue. In Group II, 55% of patients had spikes over the tumor
      bed and 89% of patients had spikes in the surrounding tissue. Spike distribution
      and discharge rate did not correlate with outcome. On postresection ECoG, 60% of
      patients in Group I and 67% of patients in Group II had residual spikes. In Group
      I, 46% of patients had spikes along the margin of resection and 26% of patients
      had extramarginal spikes. In Group II, 50% had spikes along the margin of
      resection and 67% of patients had extramarginal spikes. CONCLUSIONS: The
      difference in spike distribution in the extramarginal area between the 2 groups
      was not statistically significant, but showed a trend toward a relationship
      between postresection spikes and seizure recurrence.

PMID- 9579961
TI  - Oral gabapentin disposition in patients with epilepsy after a high-protein meal.
AB  - PURPOSE: To study the interaction between gabapentin (GBP) and high-protein
      meals, 12 patients with epilepsy were administered this drug both while in a
      fasting state and after a high-protein meal. METHODS: After having acquired their
      informed consent, the patients (suffering from partial complex seizures resistant
      to other anticonvulsants) were randomly assigned to 2 groups of 6 subjects. Each
      subject was treated in a fasting state with a single 400 (group A) or 800 (group
      B) mg GBP oral dose. After 24 h, the GBP dose regimen was repeated, but was given
      after a high-protein meal. Serum GBP concentrations were measured by LC-Mass at
      baseline and 0.5, 1, 2, 3, 5, 7, 9, 12, and 24 h. Saliva GBP concentrations were
      determined at baseline and 2, 4.8, and 12 h. GBP urinary excretion was determined
      at 0-4, 4-8, and 8-12 h intervals. The following kinetic parameters were
      calculated: area under the concentration time curve from zero time to 24 h after
      the dose, AUC 0-24 h; maximal serum concentration, Cmax; time to the maximal
      serum concentration, Tmax; absorption rate constant, ka; elimination rate
      constant, beta; elimination half-time, t1/2beta. Student's t test for paired
      data, with significance assigned at P < 0.05, was used. RESULTS: No statistically
      significant differences were seen in GBP serum or saliva concentrations or in its
      urinary excretion (both in A or B group) between fasting and after the high
      protein meal. CONCLUSIONS: High-protein meals do not seem to interfere with oral
      disposition of GBP.

PMID- 9579962
TI  - Epilepsy in developing countries.
AB  - On June 6th and 7th, 1996, an international workshop on specific aspects of
      epilepsy in the developing world was organized in Geneva by the chairman of the
      ILAE Commission of Epilepsy in Developing Countries, P. Jallon, involving members
      of the ILAE, the World Health Organization (WHO), and a network of people who
      work with epilepsy patients in developing countries. Those taking part included
      all the members of the ILAE Commission on Epilepsy in Developing Countries, the
      chairmen of the ILAE Commissions on Tropical Diseases, Epidemiology, Education,
      Economics, and Drugs, as well as the president, treasurer, and past president of
      the ILAE; and the president of the IBE, Hanneke de Boer. There were
      representatives from Eastern European countries (Russia, Slovenia, Turkey), South
      America (Brazil, Colombia, Uruguay, Ecuador, Venezuela), Africa (Ethiopia,
      Senegal, South Africa, Togo, Tunisia), and Asia (India, Indonesia, Pakistan, Sri
      Lanka, The Philippines and China). Representatives from WHO joined the meeting on
      the last day (Drs. L. Prilipko, A. Janca, and C. L. Bolis). Three major topics
      were considered--epidemiology, medical assessment, and therapeutic aspects as
      well as some economic and social aspects of the disease. A second mission of this
      meeting was to work with WHO representatives to develop a program for action to
      care for people with epilepsy in these countries.

PMID- 9579963
TI  - Dipole modeling of interictal rolandic spikes and median nerve SEPs in children
      with benign rolandic epilepsy (BREC)

PMID- 9579964
TI  - Outcomes after seizure recurrence in people with well-controlled epilepsy and the
      factors that influence it.

PMID- 9579965
TI  - Fatal occupational injuries--United States, 1980-1994.
AB  - CDC's National Institute for Occupational Safety and Health (NIOSH) monitors
      occupational injury deaths through death certificates compiled for the National
      Traumatic Occupational Fatalities (NTOF) surveillance system. Previous reports
      analyzed data from 1980-1989. This report updates these estimates on the
      magnitude of work-related injury deaths for the United States from 1980 through
      1994, the most recent year for which data are available from this system, and
      identifies high-risk industries and occupations at national and state-specific
      levels. The findings indicate that the annual total number of deaths and crude
      death rates decreased from 7405 (7.5 per 100,000 workers) in 1980 to 5406 (4.4
      per 100,000 workers) in 1994.

PMID- 9579966
TI  - Surveillance for nonfatal occupational injuries treated in hospital emergency
      departments--United States, 1996.
AB  - CDC's National Institute for Occupational Safety and Health (NIOSH) uses the
      National Electronic Injury Surveillance System (NEISS) for surveillance of
      nonfatal occupational injuries treated in hospital emergency departments (EDs).
      This report, based on 1996 NEISS data, is the first since 1983 to provide updated
      national estimates of the magnitude and risk for nonfatal occupational injuries
      treated in EDs; the findings indicate that the workers at highest risk are young
      and male.

PMID- 9579967
TI  - Corneal decompensation after intraocular ophthalmic surgery--Missouri, 1998.
AB  - During January 8-14, 1998, six of eight patients undergoing elective intraocular
      surgery at a Veterans Affairs medical center (VAMC) in St. Louis, Missouri,
      developed corneal endothelial decompensation (corneal edema and opacification) <
      or =24 hours after surgery. All had been operated on with instruments sterilized
      by the Abtox Plazlyte system (Abtox, Inc., Chicago, Illinois). This report
      summarizes the results of the investigation of these cases and indicates that
      using the Abtox Plazlyte system to sterilize opthalmologic surgical equipment led
      to corneal decompensation.

PMID- 9579968
TI  - Diagnosis and reporting of HIV and AIDS in states with integrated HIV and AIDS
      surveillance--United States, January 1994-June 1997.
AB  - Recent reports based on acquired immunodeficiency syndrome (AIDS) surveillance
      data have highlighted substantial declines in AIDS incidence and deaths. As a
      result of improvements in treatment and care of persons infected with human
      immunodeficiency virus (HIV), surveillance of AIDS alone no longer accurately
      reflects the magnitude or direction of the epidemic. Current public health and
      clinical recommendations promote early diagnosis and treatment of HIV disease.
      Data on persons in whom HIV infection is diagnosed before AIDS is diagnosed are
      needed to determine populations in need of prevention and treatment services.
      This report examines data for persons aged > or =13 years in whom HIV infection
      was diagnosed in 25 states that conducted name-based HIV surveillance in addition
      to AIDS surveillance during January 1994-June 1997. Provisional data indicate
      that declines in AIDS incidence in these states were not accompanied by
      comparable declines in the number of newly diagnosed HIV cases.

PMID- 9580028
TI  - Extracellular phospholipases as universal virulence factor in pathogenic fungi.
AB  - Microbial pathogens use a number of genetic strategies to invade the host and
      cause infection. These common themes are found throughout microbial virulence
      factors. Secretion of enzymes, such as phospholipase, has been proposed as one of
      these themes which is used by bacteria, parasite, and pathogenic fungi. The role
      of extracellular phospholipase as a potential virulence factor in pathogenic
      fungi, including Candida albicans, Cryptococcus neoformans and Aspergillus has
      gained credence recently. In this address data implicating phospholipase as a
      virulence factor in Cryptococcus neoformans and Aspergillus fumigatus will be
      presented. This will be followed by a more detailed description of our molecular
      and biochemical approaches we used to more definitively delineate the role of
      phospholipase in the virulence of C. albicans. First, we purified the
      phospholipase B protein, the dominant phospholipase secreted by C. albicans,
      obtained the amino acid sequence of its N-terminus and an internal peptide
      fragment, and used this information to clone the gene encoding the protein using
      a PCR-based approach. Nucleotide sequence analysis revealed an ORF of 1818 bp
      that predicted for a pre-protein of 605 amino acid residues. The deduced amino
      acid sequences of the cloned gene (PLB 1) showed 42.3%, 45%, and 47.8% overall
      sequence identity, with the reported sequences of phospholipase B cloned from
      Penicillium notatum, Saccharomyces cerevisiae, and Saccharomyces rosei,
      respectively. Second, using targeted gene disruption, URA blaster, we created C.
      albicans null mutants which failed to secrete phospholipase B. Third, we tested
      the ability of these isogenic strain pairs to cause lethality using a murine
      model of hematogenously disseminated candidiasis. Our data demonstrate that the
      parent phospholipase-producing strain caused more fatality in mice, while the
      null phospholipase-deficient strain was avirulent. Importantly, the parent and
      null mutants had similar growth and germination rates. These data prove that
      phospholipase B is essential for candidal virulence, and pave the way for studies
      directed at determining the mechanism/s through which phospholipase modulate
      candidal virulence. Understanding phospholipase as a common theme in fungal
      pathogenicity is critical for developing new antifungal strategies based on anti
      virulence.

PMID- 9580029
TI  - [A search for specific genes working on the process of mycelial growth in Candida
      tropicalis].
AB  - Ethanol has been reported to cause mycelial growth in Candida tropicalis Pk233.
      Cultivation with ethanol in synthetic media containing glucose gave biphasic
      growth curves. During the first growth phase, there was an accumulation of
      swollen spherical yeast cells, instead of the oblong ones observed in the control
      culture, followed by the appearance of spherical daughter cells in chains. During
      the second growth phase, pseudohyphal cells appeared, projecting from the swollen
      yeast cells.Subtractive cloning was performed on cDNAs from both cultures to
      isolate genes expressed during the first phase, correlating to the process of
      ethanol induced hyphal growth. Subtracted cDNAs identified by homology search
      included a homologue of URP2 coding ribosomal protein S20, a homologue of nmt1
      coding a regulator gene working on thiamine metabolism, and a homologue of MSG5
      coding tyrosine phosphatase. Roles of these cloned homologues were discussed on
      the process of mycelial growth in this organism.

PMID- 9580030
TI  - [Rbf1 (RPG-box binding factor), a transcription factor involved in yeast-hyphal
      transition of Candida albicans].
AB  - The major fungal pathogen for fungal diseases which have become a major medical
      problem in the last few years is Candida albicans, which can grow both in yeast
      and hyphae forms. This ability of C. albicans is thought to contribute to its
      colonization and dissemination within host tissues. In a recent few years,
      accompanying the introduction of molecular biological tools into C. albicans
      organism, several factors involved in the signal transduction pathway for yeast
      hyphal transition have been identified. One MAP kinase pathway in C. albicans,
      similar to that leading to STE12 activation in Saccharomyces cerevisiae, has been
      reported. C. albicans strains mutant in these genes show retarded filamentous
      growth on a solid media but no impairment of filamentous growth in mice. These
      results suggest two scenarios that a kinase signaling cascade plays a part in
      stimulating the morphological transition in C. albicans, and that there would be
      another signaling pathway effective in animals. In this latter true hyphal
      pathway, although some candidate proteins, such as Efg1 (transcription factor),
      Int1 (integrin-like membrane protein), or Phr1 (pH-regulated membrane protein),
      have been identified, it is still too early to say that we understand the whole
      picture of that cascade. We have cloned a C. albicans gene encoding a novel DNA
      binding protein, Rbf1, that predominantly localizes in the nucleus, and shows
      transcriptional activation capability. Disruption of the functional RBF1 genes of
      C. albicans induced the filamentous growth on all solid and liquid media tested,
      suggesting that Rbf1 might be another candidate for the true hyphal pathway.
      Relationships with other factors described above, and the target (regulated)
      genes of Rbf1 is under investigation.

PMID- 9580031
TI  - Drug pumping mechanisms in Candida albicans.
AB  - Multiple drug resistance is becoming a major problem in the treatment of AIDS
      patients with oropharyngeal candidosis. Candida albicans strains isolated from
      candidosis patients who do not respond to fluconazole therapy often show azole
      drug resistance which usually correlates with the expression of C. albicans CDR1,
      CDR2 or BENr genes, encoding potential drug efflux pumps. The objective of this
      study was to develop a yeast secretory vesicle transport assay and use this
      system to study the pumping function of Cdr1 and Benr. The C. albicans CDR1 and
      BEN r genes were cloned separately into plasmid pVT101-U, to form plasmids
      pKY1011 and pKN5001 respectively. Plasmids pVT101-U, pKY1011 and pKN5001 were
      transformed into Saccharomyces cerevisiae SY1, a sec6-4 mutant with a temperature
      sensitive mutation in the secretory pathway. SY1 cells transformed with pKY1011
      or pKN5001, were more resistant to fluconazole (MICs in both cases 64 microg/ml)
      than SY1 cells (MIC 32 microg/ml). In addition, cells transformed with pKY1011
      were more resistant to cycloheximide (MIC 16 microg/ml) than SY1 cells (MIC 2
      microg/ml). Intact secretory vesicles were isolated from SY1 cells expressing
      Cdr1 and these vesicles accumulated fluconazole in a time dependent manner. These
      experiments demonstrated that S. cerevisiae secretory vesicles can be used to
      examine the mechanism of fluconazole transport by putative C. albicans membrane
      pumps.

PMID- 9580033
TI  - [Regulation of gene expression in Aspergilli].
AB  - The Aspergillus oryzae Taka-amylase A (TAA) gene has been used as a model gene to
      characterize the regulatory mechanisms of gene expression in Aspergilli. TAA gene
      contained a typical eukaryotic promoter with a TATA box and putative regulatory
      elements such as a CCAAT sequence in its 5'-noncoding region. A nuclear protein
      designated AnCP bound to the CCAAT sequence. Replacement of the CCAAT sequence
      with CGTAA was found to abolish the binding of AnCP and to have an inhibitory
      effect on taa promoter activity. Although AnCP was not purified to homogeneity,
      AnCP appeared to have an apparent molecular mass of approximately 120 kDa. In
      Saccharomyces cerevisiae, the CCAAT-binding HAP complex is a heteromeric protein
      comprising at least four subunits (yHAP2, yHAP3, yHAP4 and yHAP5) and is involved
      in the regulation of genes responsible for oxidative phosphorylation. A gene
      designated hapC with significant homology to yHAP3 has been isolated from A.
      nidulans by Hynes et al. We expressed hapC gene as a fusion protein with MalE in
      E. coli, purified HapC protein and prepared anti-HapC antiserum. The MalE-HapC
      fusion protein was able to substitute for the authentic HapC in AnCP.
      Furthermore, addition of the anti-HapC antiserum to the DNA binding reaction
      mixture retarded the mobility of the shifted band. These indicate clearly that
      HapC protein acts as a subunit of AnCP and that AnCP is a counterpart of the
      yeast Hap complex.

PMID- 9580032
TI  - [Molecular cloning of Candida albicans phospholipase D].
AB  - Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine, a major
      substrate, to phosphatidic acid and choline, and its activity is regulated by a
      variety of hormones, growth factors, and other extracellular signals in mammalian
      cells. Thus, it is now recognized as a signal transducing enzyme such as
      phosphatidylinositol-specific phospholipase C, adenylate cyclase, or protein
      tyrosine kinases. Furthermore, recent findings that regulation by members of the
      ADP-ribosylation factor (ARF) and Rho families of monomeric GTP-binding protein
      suggest roles of PLD in intracellular vesicle traffi-cking, morphological
      changes, and mitogenic signaling process. In Saccharomyces cerevisiae, PLD gene
      has been cloned and revealed to be essential for meiosis. In contrast, little is
      known about PLD in Candida albicans. As a first step to understand possible
      physiological roles of PLD in C. albicans, we cloned a PLD gene from a C.
      albicans genomic DNA library. Deduced amino acid sequence analysis showed the
      structural similarity to mammalian, yeast, and plant PLDs. It was also suggested
      employing RT-PCR (reverse transcriptase polymerase chain reaction) that an
      isozyme of C. albicans PLD was present.

PMID- 9580034
TI  - Molecular microbiology of Pneumocystis carinii.

PMID- 9580035
TI  - [Two cases of dermatophytosis of the external auditory meatus].
AB  - We report two cases of dermatophytosis of the external auditory meatus. Case 1: A
      44-year-old man suffered from severe itching in the right external auditory
      meatus for a year, and had also had tinea unguium for several years. He visited
      our outpatient clinic because of scaly erythema which had developed on the
      auricle. Otoscopic examination revealed yellow-brown dry cerumen and redness from
      the cartilaginous to the bony portion of the external auditory meatus. Case 2: A
      14-year-old boy, the son of Case 1, suffered from severe itching in the left
      external auditory meatus. He scratched the auditory meatus with an earpick which
      his father had used. Otoscopic examination revealed a similar lesion as in the
      father's case, although he had no history of dermatophytosis elsewhere on his
      body, including the auricle. Direct examination using a KOH method of the cerumen
      from both cases demonstrated numerous fungal elements. Fungal culture identified
      Trichophyton rubrum. Both cases were successfully treated with oral itraconazole.
      We suggest that infection from father to son was transferred by the earpick.

PMID- 9580036
TI  - [Anti-Candida activities of azole antifungals in the presence of lysozyme in
      vitro].
AB  - The combined effects of lysozyme and various antifungal agents were investigated
      by microbroth dilution method against Candida albicans in vitro. Synergistic anti
      Candida activity was observed between egg white lysozyme and itraconazole,
      clotrimazole, miconazole and lanoconazole. Similar, although not as clear,
      combination anti-Candida activities were seen in the cases of ketoconazole,
      bifonazole, amphotericin B and nystatin. Anti-Candida activity of fluconazole was
      not affected by the addition of lysozyme, however. Physiological roles of this
      combination effect in anti-Candida therapy by azole antifungals were discussed.

PMID- 9580037
TI  - [Two cases of tinea capitis with different clinical courses].
AB  - We report cases of two 4-year-old boys with tinea capitis who attend the same
      daynursery. Clinically, on the first visit both lesions were a superficial type,
      however we initiated treatment with a dose of 50 mg/day of oral itraconazole.
      Althougth the lesion of case 2 improved after 11 weeks of treatment, case 1
      developed to kerion celsi and required continued treatment for 22 weeks for cure.
      Microsporum canis was isolated from the hairs of both cases and MIC of
      itraconazole against both isolates was 1 micro g/ml. We specurate that secondary
      bacterial infection was responsible for the development to kelion celsi in case
      2.

PMID- 9580038
TI  - [Characterization of leukocytes, lymphocytes and lymphocyte subsets in eating
      disorders].
AB  - Mental anorexia patients have severe denutrition and high cortisol levels.
      Nervous bulimia presents a particular psychic profile. The aim of this study was
      to evaluate lymphocyte population in eating disorders in order to understand the
      effect of these disturbances on immune system. We have found that patients with
      mental anorexia or bulimia present a significant decrease of leucocytes,
      lymphocytes, CD2 and CD4. Patients with post-anorexia bulimia have no significant
      variants. There is no difference between mental anorexia and nervous bulimia.
      There is a tendential variation between mental anorexia and controls in relation
      to CD45Ra. Considering the similar patterns of immune disturbance in anorexia and
      bulimia it looks like a dominance of neuroimmune network over malnutrition. Naive
      cells are particularly sensitive to malnutrition.

PMID- 9580039
TI  - [Factors related to diagnostic reliability of bronchial biopsy in primary
      bronchogenic carcinoma].
AB  - To analyze the diagnostic reliability of bronchial biopsy (BB) in bronchogenic
      carcinoma and the impact of several factors, among them patient symptoms and
      condition, tumor characteristics and the endoscopist's and pathologist's
      experience. One hundred eighty-four BB from 151 patients diagnosed of
      bronchogenic carcinoma in our hospital in the years 1993 and 1994 were reviewed.
      We first performed single variable analysis, and later logistical regression
      analysis taking BB positivity or negativity as the dependent variable. The
      independent variables were age, tumor stage, histological type, lesion necrosis,
      number of biopsy fragments collected, size of the largest fragment, the
      endoscopist who performed the BB and the pathologist who studied the specimen.
      The diagnosis sensitivity of BB was 69.6%. The variables that significantly
      influenced diagnostic accuracy, in both the single variable and multiple
      factorial analyses, were clinical status (p < 0.0004) and necrosis (p < 0.0057)
      with odds ratios of 4.6088 and 0.3766, respectively. The patient's clinical
      status and the presence or absence of necrosis are the factors that most
      influence diagnostic accuracy in BB for bronchogenic carcinoma. The likelihood of
      obtaining a diagnosis is 4.6 greater when clinical status is severe, and 2.7
      times greater in the absence of necrosis. The experience of the bronchoscopist,
      after a learning period, and of the examining pathologist, do not appear to have
      a decisive effect on diagnostic reliability in this technique.

PMID- 9580040
TI  - [Perfusion of donor tissue improves the preservation of graft in heterotopic
      tracheal transplantation].
AB  - To assess the effect on tracheal graft preservation of perfusion of donor tissue
      with a Collins solution before extraction and immunosuppression of the recipient.
      An experimental study was performed in 36 albino rabbits with revascularized
      heterotopic cervical reconstruction of the trachea with omentum. The animals were
      distributed in four groups. Groups I (n = 9) and III (n = 9) were transplanted
      with non perfused donor tissue. Animals in groups II (n = 9) and IV (n = 9)
      received grafts perfused with Collins solution. Immunosuppression with steroids
      and cyclosporin was continued for 21 days in groups III and IV. In a mid portion
      of the trachea viewed under optical microscope, the degree of inflammation or
      circumferential necrosis was assessed on a scale of 0 to 9 by adding the scores
      for mucosa, submucosa and cartilage. The mean score for tracheal lesion was lower
      in group IV, with a likelihood of random difference of less than 5%. Perfusion of
      peritracheal tissues with Collins solution in the donor, in addition to
      immunosuppression decreases the extent of tissue damage in the tracheal graft.

PMID- 9580041
TI  - [Prevalence of hepatitis C virus and excessive consumption of alcohol in a
      nonhospital worker population].
AB  - The aim of the study was to know the prevalence of the hepatitis C virus (HCV) in
      a non hospital work population by ELISA 3.0 and PCR-Amplicor, as well as its
      relationship with excessive alcohol intake (more than 280 g/week in men and 168
      g/week in women). A transversal seroepidemiologic study was carried out in 1,109
      workers of the Empresa Nacional de Electricidad, S.A. (ENDESA). During the annual
      medical examinations (April 1993-October 1994) the amount of alcoholic beverages
      each worker had consumed over the 7 days prior to the medical examination was
      obtained by anamnesis together with a blood sample for different laboratory
      tests. Sixteen percent of the workers had had excessive alcohol intake. The
      prevalence of anti HCV antibodies in the study population was 2.4% being up to
      4.6% in the workers declaring excessive alcohol consumption and 10.4% if they
      also presented an elevation in any of the transaminases. The prevalence of the
      potentially ineffective workers was 1.46%. The prevalence of anti C antibodies by
      ELISA 3.0 was greater than expected (2.4%) significantly increasing in the
      population group which declared excessive alcohol intake, thereby demonstrating
      the relationship between alcohol and hepatitis C.

PMID- 9580042
TI  - [Nosocomial infection over three years in a neonatal intensive care unit.
      Multivariate study].
AB  - BACKGROUND: The Neonate Intensive Care Units (NICU) present high frequencies of
      hospital infections (HI) as well as patients with high intrinsic and extrinsic
      infection risks. PATIENTS AND METHODS: A prospective study of 3 years in a NICU
      was carried out. Six-hundred and five neonates with stays longer than 48 hours
      were included. A descriptive study and a predictive equation, by non-conditional
      logistic regression, were performed, including the principal HI risk factors.
      RESULTS: The HI incidence was 25.8/1,000 patients-day, and it was most frequent
      in children with weight lower than 2,500 g. The main etiologic agents were
      Streptococcus epidermis and Pseudomonas aeruginosa. The risk factors for HI in
      NICU were assisted respiration (odds ratio [OR] = 5.1; 95% CI, 2.3-11.5), low
      weight at birth (OR = 3.2; 95% CI, 1-1.08), transfusion (OR = 3.8; 95% CI, 1.4
      10.1) and central venous catheter. Validation by ROC curve was satisfactory.
      CONCLUSIONS: The incidence of HI in NICU is high, and depends on both disease
      features and instrumentation in NICU.

PMID- 9580043
TI  - [Influence of systemic arterial hypertension on mid-term survival of patients
      with acute myocardial infarction treated with fibrinolytic agents].
AB  - BACKGROUND: The purpose of this study to asses the effect of systemic arterial
      hypertension on mid-term survival of patients with acute myocardial infarction
      who received thrombolytic treatment. PATIENTS AND METHOD: We studied 202
      consecutive patients with acute myocardial infarction, admitted in the Coronary
      Care Unit of the Hospital Xeral de Galicia who received intravenous thrombolytic
      therapy within six hours from the onset of symptoms. The thrombolytics used were:
      urokinase (79.7%), rt-PA (9.9%), streptokinase (4.9%) and APSAC (5.5%). Left
      heart catheterization with coronary angiography was performed in 162 patients at
      2 weeks after infarction. Patency of the infarction-related artery (IRA) was
      classified according to Thrombolysis in Myocardial Infarction (TIMI) criteria. A
      patent artery weas defined as having TIMI grades 2 or 3 antegrade flow. RESULTS:
      Systemic arterial hypertension was found in 34.7% of patients. IRA patency (TIMI
      2-3) was demonstrated in the 75.3% of the patients. Early mortality (first month)
      was 5.4%. Multivariate analysis identified cardiogenic shock as the only variable
      with independent predictive value for early mortality. Mean follow-up was for 24
      +/- 19 months. Late mortality was 5.2% and cardiac death occurred in 4.2% of
      patients. Reinfarction occurred in 3.1% of patients. Congestive heart failure,
      arterial hypertension and reinfarction adversely affected prognosis. Actuarial
      survival at the end of follow-up period was significantly lower in patients with
      systemic arterial hypertension (70.4% vs 85.9%; p < 0.05). CONCLUSIONS: These
      data suggest that systemic arterial hypertension adversely affects mid-term
      prognosis in patients with acute myocardial infarction who received thrombolytic
      treatment.

PMID- 9580044
TI  - Risk factors for ritonavir intolerance and outcome after change to indinavir.

PMID- 9580045
TI  - [Alcohol withdrawal syndrome: clinical and analytical manifestations and
      treatment].
AB  - BACKGROUND: The aim of this study was to analyze clinical manifestations and
      treatment aspects of alcohol withdrawal syndrome. MATERIAL AND METHODS: A
      retrospective study of 212 clinical records. RESULTS: The commonest withdrawal
      effects were tremulousness (68.7%) 7 agitation (67.3%) and hallucinations (46%).
      Most patients were male. The 64% recognize a period of relative or absolute
      abstinence less than two days, and a 67.8% have been previous incident of
      withdrawal syndrome. The commonest complications during hospital stay were
      rhabdomyolysis (26%). Time of symptoms were three days and mean of
      hospitalization were 14 days. The treatment used was the correction of fluid and
      electrolyte imbalance (93%) and B vitamins (98%). In relation to the use of
      drugs, in 84% of our patients we used benzodiazepines with longer-acting, and
      clomethiazole in 50% of cases. Mortality were 0.9%. CONCLUSIONS: Patient with
      alcohol withdrawal syndrome was a male, previously drinker, with a period of
      abstinence less than two days. In addition to tremulousness and agitation, in our
      series, we wish to emphasize higher frequency of hallucinations, and the
      incidence of complications as rhabdomyolysis, despite of such response of
      treatment is good and mortality is low.

PMID- 9580046
TI  - [Adrenocortical function in patients with active pulmonary tuberculosis].
AB  - STUDY OBJECTIVE: To assess adrenal function in patients with acute
      pleuropulmonary tuberculosis (APT) and compare it with that function in patients
      with community-acquired pneumonia (CAP). PATIENTS: Over a period of 6 months all
      consecutive patients 18 years of age or older with newly diagnosed APT and CAP
      were entered into the study. MEASUREMENTS: The whole patients had the following
      investigations: 1) Serum Na+, K+ and glucose concentrations 2) Systolic and
      diastolic blood pressures. 3) An ultrasonographic study of the adrenal glands. 4)
      A standard ACTH stimulation test. RESULTS: There was no significative difference
      in the serum cortisol level between the two groups at any time of the ACTH
      stimulation test (basal, 30 and 60 minutes), neither when taking into account the
      increments between basal and 60 minutes after stimulation serum cortisol levels.
      All patients in both groups had normal ACTH stimulation test with a peak
      stimulated cortisol level at 60 minutes > 504 nmol/L. CONCLUSIONS: We did not
      find evidence of adrenal cortical dysfunction in patients with acute
      pleuropulmonary tuberculosis or with community-acquired pneumonia in our
      hospital.

PMID- 9580047
TI  - [Clinical manifestations associated with antiphospholipid antibodies].
AB  - The antiphospholipid antibodies are immunoglobulins able to join negative charge
      phospholipids. The have been related to a great variety of conditions, specially
      among connective tissue illness although the idiopathic form seems to be the most
      frequent. Their presence must be ruled out in cases of young patients with
      stroke, deep veins thrombosis, acute heart attack and woman suffer multiple
      abortions and foetal death. These antibodies appear to be related to different
      clinical entities like Sneddon syndrome. Evans syndrome, "chorea gestationis",
      migraine. The laboratory determinations are based in direct methods (ELISA, RIA,
      ...) as well as in indirect ones (activated partial thromboplastin time,
      reptilase time, ...). The appropriate management and treatment may be based upon
      clinical expression, in case of arterial thrombosis (type II APS), or deep vein
      thrombosis (Type II) long term anticoagulation is indicated; Association with
      pentoxifylline in the case of retinal thrombosis (type IIIa), Stroke (type IIIb)
      cases may require long term anticoagulation as well as aspirin. Type IV cases are
      better managed with an individualised treatment.

PMID- 9580048
TI  - [Pre-Cushing's syndrome in patients with asymptomatic adrenal mass].

PMID- 9580049
TI  - Use of ion trap gas chromatography-tandem mass spectrometry for detection and
      confirmation of anabolic substances at trace levels in doping analysis.
AB  - A procedure for detecting and confirming 23 anabolic substances and/or
      metabolites has been developed using a GC-MS-MS ion trap system in full-scan
      mode. The process used to select the precursor ion, and the optimization of the
      system parameters used to obtain the daughter ion spectra, are explained. Urine
      samples were prepared using solid-phase extraction and enzymatic hydrolysis, and
      after TMS derivatives had been formed, they were injected into the mass
      spectrometer. This method permits confirmation of the presence of anabolic
      substances at low ng ml(-1) levels without the need of further purification
      procedures on the samples. This procedure has been used on more than 2000 urine
      samples collected from sporting competitions and has made it possible to confirm
      more than 45 true positive cases which could not have been confirmed using
      routine GC-MS methods.

PMID- 9580050
TI  - Lesions described as nodular mesothelial hyperplasia are primarily composed of
      histiocytes.
AB  - It is known that, on occasion, histiocytic proliferations can be confused with
      reactive mesothelial cell hyperplasia or with a malignant process. We report four
      cases of histiocytic proliferation, two occurring in the pleura in a 23-year-old
      woman and a 78-year-old woman, respectively, one in a hernial sac of a 2-year-old
      boy, and one in the lamina propria of the bladder of a 74-year-old man with a
      noninvasive papillary transitional cell carcinoma. The morphologic features of
      the pleural lesion of the 23-year-old woman and of the hernial sac lesion of the
      2-year-old boy, as well as the bladder lesion, were similar to those reported in
      cases of the so-called nodular mesothelial hyperplasia. The pleural lesion in the
      78-year-old woman consisted of a proliferation of cells with a signet ring-like
      morphology that was originally interpreted as either an unusual form of
      mesothelial hyperplasia or a metastatic signet ring cell adenocarcinoma. Because
      of mitotic activity and some cellular atypia in the bladder lesion, the
      possibility of invasive transitional cell carcinoma into the lamina propria was
      considered before immunohistochemical studies were performed. Staining for
      keratin showed only a few positive cells in the hernial sac and pleural lesions,
      whereas most cells reacted for the histiocytic marker CD68. Immunohistochemical
      studies on the bladder lesion also demonstrated strong staining for CD68, but no
      reactivity for keratin was observed. Based on these results, it is concluded that
      all of the lesions are primarily reactive histiocytic proliferations and because
      they may occur in other locations aside from the serosal membranes, the
      designation "nodular histiocytic hyperplasia" appears to be more appropriate than
      that of nodular mesothelial hyperplasia. It is important that the reactive nature
      of these lesions be recognized because on occasion they may present high mitotic
      activity or may show signet ring-like morphology and thus they can be confused
      with a malignancy.

PMID- 9580051
TI  - Receptor-mediated endocytosis in kidney proximal tubules: recent advances and
      hypothesis.
AB  - Preparation of kidney proximal tubules in suspension allows the study of receptor
      mediated endocytosis, protein reabsorption, and traffic of endosomal vesicles.
      The study of tubular protein transport in vitro coupled with that of the function
      of endosomal preparation offers a unique opportunity to investigate a receptor
      mediated endocytosis pathway under physiological and pathological conditions. We
      assume that receptor-mediated endocytosis of albumin in kidney proximal tubules
      in situ and in vitro can be regulated, on the one hand, by the components of the
      acidification machinery (V-type H+-ATPase, Cl(-)-channel and Na+/H+-exchanger),
      giving rise to formation and dissipation of a proton gradient in endosomal
      vesicles, and, on the other hand, by small GTPases of the ADP-ribosylation factor
      (Arf)-family. In this paper we thus analyze the recent advances of the studies of
      cellular and molecular mechanisms underlying the identification, localization,
      and function of the acidification machinery (V-type H+-ATPase, Cl(-)-channel) as
      well as Arf-family small GTPases and phospholipase D in the endocytotic pathway
      of kidney proximal tubules. Also, we explore the possible functional interaction
      between the acidification machinery and Arf-family small GTPases. Finally, we
      propose the hypothesis of the regulation of translocation of Arf-family small
      GTPases by an endosomal acidification process and its role during receptor
      mediated endocytosis in kidney proximal tubules. The results of this study will
      not only enhance our understanding of the receptor-mediated endocytosis pathway
      in kidney proximal tubules under physiological conditions but will also have
      important implications with respect to the functional consequences under some
      pathological circumstances. Furthermore, it may suggest novel targets and
      approaches in the prevention and treatment of various diseases (cystic fibrosis,
      Dent's disease, diabetes and autosomal dominant polycystic kidney disease).

PMID- 9580052
TI  - [Factors predicting survival in patients on peritoneal dialysis].
AB  - OBJECTIVE: To determine the factors associated with survival in a cohort of 74
      patients with end-stage renal disease (ESRD) undergoing chronic peritoneal
      dialysis (CPD). SETTING: The study was carried out at a general hospital of the
      Instituto Mexicano del Seguro Social. DESIGN: Analysis of a retrolective cohort
      under a nested case control design. PATIENTS AND METHODS: The variables studied
      included age, gender, cause of ESRD (diabetic or non-diabetic), socioeconomic
      status, modality of CPD (intermittent vs continuous ambulatory peritoneal
      dialysis), catheters per patient, rate of peritonitis, levels of serum creatinine
      and albumin at the beginning of the CPD. RESULTS: During a 75.1 years-patient
      follow up, there were 41 deaths (cases). The main cause of death was peritonitis.
      The cumulated survival of the 74 patients was 64%, 29% and 13% at 12, 24 and 33
      months, respectively. Intermittent peritoneal dialysis, the rate of peritonitis
      and the level of basal serum albumin were associated with a decreased survival in
      a univariate analysis. Only a high rate of peritonitis was associated with an
      increase in mortality rate independent from other variables (p = 0.002).
      CONCLUSIONS: The probability of survival in ESRD in our hospital was low in
      relation to other nephrology departments of Mexico and other countries. A high
      rate of peritonitis proved to be an important independent predictor of a lesser
      survival rate in patients under CPD in our institution.

PMID- 9580054
TI  - [Hemochromatosis associated with hereditary spherocytosis].
AB  - Hereditary spherocytosis is a chronic hemolytic anemia that very infrequently
      produces severe iron overload. Only 15 cases of hereditary spherocytosis
      associated with hemochromatosis have been described previously. It was initially
      thought that hemochromatosis was the result of the increase of iron stores
      secondary to chronic hemolysis. Afterwards, it became apparent that iron overload
      could appear in patients splenectomized. This fact suggested that spherocytosis
      and idiopathic hemochromatosis could be inherited independently. We describe the
      case of a 45-year-old man, with known hereditary spherocytosis, splenectomized at
      5 years of age, who developed iron overload which affected his heart, liver and
      pancreas.

PMID- 9580053
TI  - [Preliminary results of the study of neuronal death and the expression of bcl-2
      protein in Alzheimer's disease].
AB  - Alzheimer's disease (AD) is a degenerative central nervous system disorder where
      beside the histopathologic features of senile plaques and neurofibrillary tangles
      there is an important neuronal loss. It has been suggested that this neuronal
      death occurs via an apoptotic mechanism. Recognition of apoptotic cells is
      possible by an in situ end-labeling technique which identify the 3'-OH termini of
      DNA strands breaks through the incorporation of labeled nucleotides with the
      enzyme terminal-deoxinucleotidyl transferase (Tdt). We have applied this
      technique and high densities of apoptotic cells were found in 5 AD brains
      compared to 5 age-matched normal samples. We studied by immunohistochemical
      analyses the expression of the antiapoptotic protein bcl-2. We have not found
      neuronal bcl-2 immunoreactivity and we found an increased expression of bcl-2 by
      astrocytes compared to controls, this fact may aid glial survival or may have a
      deleterious effect on neuronal viability.

PMID- 9580055
TI  - A comparison of the effects of fentanyl and propofol on left ventricular
      contractility during myocardial stunning.
AB  - BACKGROUND: The intravenous anaesthetic propofol has been shown to possess free
      radical scavenging activity and calcium channel blocking effects in a number of
      in vitro models. We decided to compare the effects of propofol with those of
      fentanyl on myocardial contractility during and after ischaemia to determine
      whether propofol could protect the heart and improve recovery of ventricular
      contractile function in open-chested dogs. METHODS: Twenty adult beagles were
      acutely instrumented, under halothane anaesthesia, to measure ECG; aortic, left
      ventricular pressures; cardiac output; coronary flow; and segmental lengths in
      the regions perfused by the left anterior and left circumflex coronary arteries.
      After surgery and a stabilisation period halothane anaesthesia was terminated and
      fentanyl (100 microg x kg[-1] bolus followed by 2 microg x kg[-1] x min[-1]
      infusion; n=10) or propofol (5 mg x kg[-1] bolus followed by 0.3 mg x kg[-1] x
      min[-1] infusion; n=10) anaesthesia commenced. After a stabilisation period the
      LAD coronary artery was occluded for 10 min and then reperfused for 3 h.
      Measurements were taken throughout the protocol. RESULTS: We found no significant
      difference in recovery of contractile function between propofol and fentanyl as
      assessed by normalised preload recruitable work area (50+/-10 vs 47+/-16%),
      normalised systolic shortening (36+/-12 vs 48+/-14%) and peak left ventricular
      dP/dt (1665+/-276 vs 1846+/-151 mmHg x s[-1]) at the end of reperfusion.
      CONCLUSION: We conclude that at the concentration used in this study propofol
      shows no improvement in contractility during "stunning" when compared to
      fentanyl.

PMID- 9580057
TI  - [Unilateral neonatal cystic disease of the kidney as first manifestation of
      tuberous sclerosis].
AB  - OBJECTIVE: To report a case of unilateral cystic disease in a neonatal kidney as
      the first manifestation of tuberous sclerosis, with special reference to the
      diagnostic difficulties. METHODS: The pathological and clinical features of
      unilateral cystic kidney disease, which was basically segmental, are described.
      This condition had been detected in a newborn at physical examination. RESULTS:
      The pathological findings of the kidney cysts were characteristic of tuberous
      sclerosis, which allowed us to rule out a renal tumor. The clinical course
      confirmed the histological diagnosis. CONCLUSIONS: The reported cases of
      bilateral cystic kidney disease as the first manifestation of tuberous sclerosis
      are few and only one case with unilateral involvement has been reported in the
      English literature. In the case described herein, biopsy proved to be very useful
      in the diagnosis of the disease since the kidney cysts had specific histological
      features.

PMID- 9580056
TI  - [Unilateral renal agenesis associated with pelvic renal ectopy].
AB  - OBJECTIVE: To describe a rare case of right renal agenesia and left pelvic
      ectopy. To our knowledge, only 10 such cases have been reported in the world
      literature. METHODS: A 76-year-old male patient who consulted for irritative
      prostatic syndrome is described. Patient evaluation included IVP and CT. RESULTS:
      IVP revealed the absence of the right kidney in addition to an anomalous position
      of the left kidney. The foregoing findings were confirmed by CT. CONCLUSION: This
      uncommon congenital anomaly is essentially asymptomatic and is generally
      diagnosed in infants through its complications. In the case described herein,
      however, this anomaly had been incidentally detected during IVP and CT assessment
      of a 76-year-old patient who had consulted for irritative prostatic syndrome.

PMID- 9580058
TI  - [Ureteral hydronephrosis secondary to appendicular abscess].
AB  - OBJECTIVE: To report a case of ureterohydronephrosis secondary to an undiagnosed
      appendiceal abscess. METHODS/RESULTS: Herein we describe a case of a 4-year-old
      girl with right ureterohydronephrosis arising from extrinsic compression of the
      right ureter due to an undiagnosed appendiceal abscess. The patient was treated
      with intravenous antibiotics and the abscess was drained. Regular isotope and US
      assessments showed both the residual retroperitoneal fibrosis and renoureteral
      dilation had decreased. CONCLUSIONS: Acute appendicitis is still the most common
      cause of emergency abdominal operations in children. Although the symptoms are
      easily recognizable and generally lead to the correct diagnosis in most cases,
      the peculiarities of childhood can lead to errors in the diagnosis resulting in
      the complications reported herein. We emphasize the usefulness of ultrasound in
      the diagnosis and conservative treatment is advocated.

PMID- 9580059
TI  - Ca2+ dependence of the response of three adenosine type receptors in rat
      hepatocytes.
AB  - The effect of three different receptor-specific adenosine agonists on the rate of
      ureagenesis by isolated rat hepatocytes and the dependence on the external free
      Ca2+ concentration ([Ca2+]e) were investigated. In the presence of high [Ca2+]e
      all adenosine receptor agonists increased ureagenesis to similar levels. However,
      with low [Ca2+]e the effects of each agonist varied as follows: (i) the adenosine
      A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine, increased ureagenesis
      depending partially on [Ca2+]e, (ii) the adenosine receptor A2 agonist, 2-p-(-2
      carboxy-ethyl) phenethylamino-5'-N-ethylcarboxyamido adenosine hydrochloride,
      increased ureagenesis independently of [Ca2+]e and (iii) in contrast, the
      adenosine receptor A3 agonist N6-2-(-4-aminophenyl) ethyladenosine, increased
      ureagenesis only in the presence of high [Ca2+]e. The adenosine receptor A1
      antagonist, 1-allyl-3,7-dimethyl-8-phenyl xanthine, inhibited the effect of the
      adenosine receptor A1 agonist on ureagenesis, but not the effect of the adenosine
      A2 or A3 receptor agonists. The adenosine A2 receptor antagonist, 3,7-dimethyl-1
      propargylxanthine, inhibited only the effect of the adenosine A2 receptor
      agonist. Thus, in addition to A1 and A2 type adenosine receptors, rat hepatocytes
      possess an A3-like adenosine receptor which responds to the addition of an
      adenosine A3 agonist by accelerating ureagenesis a [Ca2+]e dependent manner.
      Moreover, it was observed that in the presence of extracellular Ca2+ each agonist
      increased [Ca2+]i and this effect was inhibited by the appropriate specific
      antagonist.

PMID- 9580060
TI  - [Fertility and viability study of ovine hydatid cysts].
AB  - BACKGROUND: The purpose of this work is to analyze the fertility of the hydatid
      cysts from ovine, animal species of great epidemiological interest in the hydatid
      disease, and the ability of the gerbil (Meriones unguiculatus) as model
      experimental for the study "in vivo" of this hidatyd disease as preliminary phase
      of therapeutic studies. METHODS: It has been carried out a study of the fertility
      and viability of hydatid cysts from lungs and livers of ovine from Castilla and
      Leon by examination and evaluation of parameters among these is the production of
      a secondary hydatid disease in laboratory animals. RESULTS: The total cystic
      index was 8.57 cysts by infested ovine (5.97 cysts by infested lung and 5.57
      cysts by infested liver). The fertility percentage obtained in hydatid cysts from
      ovine with "in vitro" viables protoescoleces was 43.97% being 43.02% a pulmonary
      cysts and 46.16% in hepatic cysts. The viability of protoscoleces was
      demonstrated by production of a secondary hydatid disease in 100% of gerbils
      infested. CONCLUSIONS: It is emphasized the validity of the criteria used to
      study the viability "in vitro" of the protoescoleces from hydatid cysts of origin
      ovine. The secondary hydatid produced in gerbil leads us to consider them as
      experimental animal for investigation "in vivo" of hydatid disease of origin
      ovine.

PMID- 9580061
TI  - Nasal pungency and odor of homologous aldehydes and carboxylic acids.
AB  - Airborne substances can stimulate both the olfactory and the trigeminal nerve in
      the nose, giving rise to odor and pungent (irritant) sensations, respectively.
      Nose, eye, and throat irritation constitute common adverse effects in indoor
      environments. We measured odor and nasal pungency thresholds for homologous
      aliphatic aldehydes (butanal through octanal) and carboxylic acids (formic,
      acetic, butanoic, hexanoic, and octanoic). Nasal pungency was measured in
      subjects lacking olfaction (i.e., anosmics) to avoid odor biases. Similar to
      other homologous series, odor and pungency thresholds declined (i.e., sensory
      potency increased) with increasing carbon chain length. A previously derived
      quantitative structure-activity relationship (QSAR) based on solvation energies
      predicted all nasal pungency thresholds, except for acetic acid, implying that a
      key step in the mechanism for threshold pungency involves transfer of the inhaled
      substance from the vapor phase to the receptive biological phase. In contrast,
      acetic acid - with a pungency threshold lower than predicted - is likely to
      produce threshold pungency through direct chemical reaction with the mucosa. Both
      in the series studied here and in those studied previously, we reach a member at
      longer chain-lengths beyond which pungency fades. The evidence suggests a
      biological cut-off, presumably based upon molecular size, across the various
      series.

PMID- 9580062
TI  - [Lupus nephropathy treated with cyclosporine A. Report of 3 cases].
AB  - Three patients are reported who had systemic lupus erythematosus and membrane
      proliferative glomerulonephritis. These patients failed to respond to intravenous
      cyclophosphamide and steroids and were then changed to receive oral cyclosporine
      A, at a dose of 5 mg/kg/day. The three patients showed remission of disease,
      symptoms, and renal and immunological parameters, with minimal secondary effects.
      The medical literature was reviewed and cyclosporine A is suggested to be a
      therapeutical choice for patients with lupus nephropathy even when they do not
      respond to other immunosuppressive regimes, such as pulse cyclophosphamide.

PMID- 9580063
TI  - [Synchronous presentation of thyroid carcinoma and malignant lymphoproliferative
      disease: report of 3 cases].
AB  - Multiple primary neoplasms are increasing in clinical practice, which is mainly
      due to the longer survival of cancer patients. Radiotherapy at an early stage of
      Hodgkin disease or lymphoma is well known to be associated with the future
      occurrence of secondary thyroid cancer. Nevertheless, the synchronous
      presentation of these two types of neoplasms is exceptional. We report here three
      cases of synchronic diagnosis of thyroid carcinoma and a malignant
      lymphoproliferative disease in patients who had not previously received
      radiotherapy nor chemotherapy. In malignant tumours of synchronic presentation,
      there is usually and underlying genetic predisposition involved in the etiology.
      In our patients, no carcinogenic environmental factor was demonstrated and, while
      this neoplastic association might be casual, an investigation on the possible
      individual predisposing factors would be warranted.

PMID- 9580064
TI  - [A 53-year old infertile male with bronchiectasis].

PMID- 9580065
TI  - [Affective factors in the evolution of catatonia: a report of two cases of
      catatonia in twins].
AB  - The evolution of two twin patients diagnosed of catatonic schizophrenia is
      studied, through their clinical history, and the incidence of affective factors
      on the evolution of their clinical chart is evaluated. With regard to the
      results, the diagnosis of schizoaffective disorder is postulated.

PMID- 9580066
TI  - [Neurinoma of the thyroid gland].
AB  - Schwannomas are solitary neurogenic tumors that arise from cells of the neural
      sheat. They grow slowly and represent a proliferation of Schwann cells.
      Extracranial neurogenic tumors of the head and neck are uncommon. We describe a
      case of solitary cervical schwannoma placed in the thyroid area. And recall the
      histology, the nerves more frequently involved, diagnostic tests and the
      treatment of these nervous tumors.

PMID- 9580067
TI  - [Diabetic complications and hypoacusia].
AB  - The relationship between diabetes mellitus and hypacusia has been discussed since
      the work of Jordao, in 1857. Numerous authors are openly pro this viewpoint,
      whereas other deny it. The hypoacusis is typically bilateral, progressive and of
      neurosensory nature, affecting the higher frequencies. In the etiologic aspect
      some authors bet for an angiopathic origin, but others suppose a neuropathic
      cause. We have achieved a comparative study with the aim to get some conclusions
      that could enlighten this field. Forty patients with diabetes mellitus type II
      were audiometrically examinees (at threshold and with supraliminar tests) and the
      results compared with those of a control group. We also assessed several
      complications of the disease and their possible report with the auditive
      impairment (retinopathy and neuropathy). We found out a sensorineural, bilateral
      and symmetrical hearing impairment. Employing the Man Whitney's U test we compare
      distinct groups and explain the gained outcomes. Bibliographic review of authors
      defending the vascular or the nervous starting point.

PMID- 9580068
TI  - [Severe caustic esophagitis in childhood].
AB  - OBJECTIVE: A retrospective analysis of patients treated for serious caustic
      esophagitis in our hospital was performed with the aim of defining
      epidemiological factors, initial treatment and therapeutic criteria for
      esophageal stricture with long evolution. PATIENTS AND METHODS: Thirty-four cases
      of serious caustic esophagitis treated since 1982 were analyzed surveying
      epidemiologic, clinical and endoscopy data, as well as initial medical treatment,
      dilatation session number, treatment period, complications, surgical treatment
      indications if necessary and actual situation. RESULTS: Alkaline caustic agents
      were swallowed in 71% of the cases, with dishwashing detergent being the most
      frequent (16 patients), Grade II esophagitis was noticed in 13 cases, grade III
      in 18. Established esophageal stricture was present in 3 patients when admitted.
      Repeated esophageal dilations were necessary in 13 patients (38%), with between 1
      and 21 dilatation sessions needed. Esophageal stricture persistence forced us to
      perform an esophageal substitution technique by esophagocoloplasty. Resection and
      enlargement of a short stenotic segment was performed in 1 patient. Long-term
      evolution in all cases has been satisfactory. CONCLUSIONS: We consider that
      adequate treatment of these patients includes conservative corticosteroids,
      sucralfate and anti-H2 combined with a previous endoscopy evaluation. If
      evolution turns into stricture, dilatations must be done, sometimes throughout
      years. If this treatment fails and the injury is extensive, esophagocoloplasty is
      the surgical technique of choice. Nevertheless, as any accident, the best
      treatment is good prevention.

PMID- 9580069
TI  - [Pediatric emergencies in a community health center].
AB  - OBJECTIVE: The excess of pediatric emergencies going to hospitals has been the
      subject of many studies in Spain and, on some occasions, this problem has
      attributed to the inefficiency of pediatric primary care. Our main objective was
      to evaluate whether or not our community health center is an efficient filter for
      hospital emergencies. PATIENTS AND METHODS: We conducted a prospective one year
      long study of all pediatric emergency demands within our normal office hours
      (workdays, from 08:00 to 21:00 hours). RESULTS: The total number of emergencies
      amounted to 1,294, with an average of 5.78 per day. The largest inflow occurred
      in September and the lowest in August. Most of the emergencies were between 16:00
      and 19:00 hours. Fifty percent of the patients were under 4 years of age. We made
      86 different diagnoses according to the WONCA classification. Only 10 diagnoses
      came with a frequency superior to 3%, and 60% of the emergencies were related to
      one of these 10 diagnoses. Of all pediatric emergencies, 94.7% were completely
      resolved by us. Only 60 patients (4.6%) were sent-on to hospital emergency
      services. Among these patients, 40 required traumatological or surgical
      attention, 5 ophthalmological care, 3 otorhinolaryngological care, and only 12
      exclusively needed pediatric attention. In 55.7% of the cases there was no reason
      to use the emergency channel. CONCLUSIONS: During our office hours, our community
      health center is an efficient filter for hospital pediatric emergencies.

PMID- 9580070
TI  - [Preventive use of antibiotics in neonatal surgery].
AB  - OBJECTIVE: The objective of this study was to determine the incidence of surgical
      wound infection and the impact of this on the implementation of an antibiotic
      protocol according to the type of surgery and the prevailing endogenous flora in
      our neonatology unit. PATIENTS AND METHODS: Patients' charts were retrospectively
      reviewed in order to assess the effectiveness of a protocol of surgical
      prophylaxis, comparing the incidence of postsurgical wound infection in two
      periods of time. Surgical interventions were classified according to the period
      of the study in which they were performed, before (period A) and after (period B)
      the protocol was undertaken. In addition, if the antibiotics administered fit or
      not those indicated in the protocol, it was classified as correct or not.
      RESULTS: A total of 31 (37%) of the interventions were performed in period A,
      whereas 53 (63%) were carried out in period B. No statistically significant
      differences were found between periods with regard to the proportion of
      infections 925.8% vs 15%). When prophylactic antibiotics were administered
      correctly, infection occurred in 10.2%, as compared to 31.4% when they did not
      fit the protocol (p < 0.05). The duration of the antibiotics was longer in period
      A, in infected wounds and when prophylaxis was not correct. CONCLUSIONS: The
      correct adjustment to the protocol significantly decreases the incidence of wound
      infections, as well as the duration of antibiotic use. An appropriate policy of
      antibiotic prophylaxis in surgery is advantageous in terms of economic cost and
      might prevent antibiotic resistance and avoid unnecessary toxicity.

PMID- 9580073
TI  - [An increase in the incidence of serotype C meningococcal diseases in the
      province of Sevilla].

PMID- 9580072
TI  - [Introduction to molecular biology and its application to pediatrics (8):
      additional methods for the detection of mutations. Clinical case: hemochromatosis
      in a family. Transgenic animals].

PMID- 9580071
TI  - [Functional impotence of the lower limb in an infant].

PMID- 9580074
TI  - Microsporidiosis in HIV-positive children in Madrid (Spain).
AB  - A prospective study was carried out to determine the prevalence rates of
      microsporidiosis and other enteroparasites in HIV-positive children in the Madrid
      area. HIV-positive pediatric patients from three hospitals were enrolled in the
      study. A total of 293 samples (158 stool and 127 urine) were collected from 83
      children whose mean age was 6.3 years and had a mean CD4 count of 504.7/mm3
      (range 1-2,220/mm3), 48 of whom suffered diarrhea at the time of the study.
      Microsporidia identification was investigated in stool and urine samples using
      Weber's chromotrope-based stain, IIF and PCR species-specific tests. Enteric
      parasites were identified in 32.5% of the children. Cryptosporidium sp. was the
      most common parasite encountered (14.4%), followed by Blastocytis sp. (9.6%) and
      Giardia duodenalis (8.4%). Microsporidia was only found in the stools of one
      child (1.2% of total and 2% of those with diarrhea) and Enterocytozoon bieneusi
      was demonstrated by PCR. The patient was 10 years old, presented non-chronic
      diarrhea and his CD4 count was 298/mm3. These data differ from those previously
      reported by us in HIV-positive adults (13.9%) in the same area, although this
      group showed more severely depressed CD4 lymphocyte counts than children. New
      epidemiological studies should be carried out to elucidate whether additional
      risk factors exist between these groups.

PMID- 9580076
TI  - Vascular density as a prognostic indicator for invasive ductal breast carcinoma.
AB  - Estimated vascular density obtained with the aid of antibodies against
      endothelial cells has been claimed to be an independent prognostic indicator for
      invasive ductal breast carcinoma. Since 1991 most studies have counted the number
      of vessels with the optic microscope. We have performed immunohistochemical
      staining for Factor VIII on formaldehyde-fixed, paraffin-embedded primary
      invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60
      months, who had received postoperative chemoradiation therapy. We have performed
      a manual count with a 20x objective of the vessels in the vascular hot-spot
      identified in a 4x field. We analysed the association of this factor with
      epidemiological risk factors, histopathological features, hormonal receptor
      status and p53 and c-erbB-2 expression and the influence on prognosis. In
      univariate analysis vascular density is a significant prognostic indicator in
      both node-negative and node-positive patients, together with staging, Baak's
      morphometric multiparametric index, tumour size and histological grade. However,
      in multivariate analysis only tumour staging and vascular density are independent
      prognostic factors in breast carcinoma.

PMID- 9580077
TI  - Transanal self-expanding metal stents as an alternative to palliative colostomy
      in selected patients with malignant obstruction of the left colon.
AB  - BACKGROUND: Palliative colostomy is still unavoidable in many patients with
      malignant obstruction of the left colon. This report describes an initial
      experience and follow-up in a small series of patients with left-sided colon
      obstruction in whom transanal self-expanding metal stent (SEMS) placement was
      attempted for palliative purposes. METHODS: Palliative transanal SEMS placement
      was attempted in 11 patients with malignant obstruction of the rectosigmoid
      region. The selection criteria included patients with advanced pelvic disease,
      peritoneal carcinomatosis and/or multiple parenchymatous metastatic disease.
      Wallstent oesophageal endoprostheses were used, and the technique was carried out
      by interventional radiologists. RESULTS: The technique succeeded in relieving the
      obstruction in seven patients, and surgical intervention was prevented in six.
      Five of these six patients died with an unobstructed colon from 26 days to 7
      months after SEMS placement. The technique failed in four patients, three of whom
      underwent emergency colostomy. CONCLUSION: Transanal SEMS placement is an
      appealing method for the relief of obstruction in selected patients, obviating
      the need for palliative colostomy.

PMID- 9580075
TI  - A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG
      antivenoms for Bothrops snake bites in Uraba, Colombia. The Regional Group on
      Antivenom Therapy Research (REGATHER).
AB  - The therapeutic efficacy and the incidence of early antivenom reactions (EARs)
      were compared in a clinical trial performed in 79 patients bitten by Bothrops sp.
      in Uraba, Colombia. Patients were randomized into three groups according to the
      antivenom administered: A (n = 30, Butantan polyspecific, pepsin-digested
      Bothrops antivenom); B (n = 27, Butantan polyspecific, whole IgG Bothrops
      antivenom); and C (n = 22, Colombian commercial, monovalent, whole IgG Bothrops
      antivenom). The groups were comparable in all clinical and epidemiologic aspects;
      33 patients had mild, 22 moderate, and 24 severe envenoming. At the doses used
      (two, four, and six vials [10 ml/vial] for mild, moderate, and severe
      envenomings, respectively) there were no differences between the antivenoms in
      restoring normal hemostatic parameters within 24 hr. The evolution of local
      envenoming was comparable in the three groups. Serum venom/antivenom kinetics
      determined by ELISA showed a complete clearance of venom levels 1 hr after
      treatment in mild/moderate envenomings. In severe cases, venom levels remained
      detectable up to 24 hr and recurrence of antigenemia was observed in some cases.
      Antivenom concentrations remained at high levels up to 24 hr of treatment. The
      incidence of EARs was significantly different in the groups: A (36.7%), B
      (11.1.%), and C (81.8%). There were no life-threatening anaphylactic reactions.
      We conclude that the efficacy of the three antivenoms was similar in neutralizing
      human Bothrops envenomings and that the production of whole IgG antivenoms by
      caprylic acid fractionation is a good alternative for reducing the incidence of
      EARs.

PMID- 9580078
TI  - Entamoeba histolytica: collagen-induced AP-1 DNA binding activity.
AB  - The interaction of Entamoeba histolytica trophozoites with collagen induces the
      synthesis and release of electron-dense granules containing a collagenase
      activity that is an important factor in the pathogenicity of the parasite. The
      binding is thought to be mediated by an 'integrin-like' collagen receptor. In the
      signal transduction mechanisms activated by collagen, pp125FAK and p42MAPK are
      involved. Using immunoprecipitation assays coupled to Western blot analysis, we
      demonstrate here the collagen-dependent association of paxillin and Src with
      pp125FAK. Furthermore, collagen induces a time-dependent increase in the DNA
      binding activity of the activator protein 1, which is well correlated with an
      increase in Fos expression. Our results suggest that a stimulus-transcription
      coupling triggered by collagen in E. histolytica trophozoites might activate or
      repress genes involved in tissue invasiveness.

PMID- 9580080
TI  - The relationship between dental age, bone age and chronological age in 54
      children with short familial stature.
AB  - Patients with short familial stature (SFS) have a short body height, but their
      bone age is normal. The aim of this research was to assess dental maturity in 54
      patients with SFS, aged from 4 to 15 1/2 years. Bone age was judged from
      radiographs of the left wrist, and dental age from orthopantomograms. Dental age
      was retarded in relation to chronological age and to bone age.

PMID- 9580079
TI  - Coexpression of mRNA for the full-length neurotrophin receptor trk-C and trk-A in
      favourable neuroblastoma.
AB  - Neuroblastoma, a childhood tumour of the sympathetic nervous system, may
      sometimes regress spontaneously in infants, or progress to a poor clinical
      outcome despite intensive therapy. Neuroblastomas express neurotrophin receptors
      and high levels of mRNA for trk-A correlates with favourable outcome, whereas trk
      B mRNA is expressed by more unfavourable tumours. Using a sensitive RNase
      protection assay, mRNA expression for the neurotrophin receptor trk-C was
      investigated in 50 tumour samples from 45 children at different stages including
      metastatic and relapsing tumour tissue, out of which 22 were also investigated
      for trk-A mRNA. Thirty-seven of 43 primary tumours (86%) showed trk-C mRNA with
      more than 300-fold difference between the highest and the lowest values. A higher
      trk-C index (trk-C mRNA/GAPDH mRNA) was associated with favourable features such
      as younger age (P = 0.009-0.003), favourable tumour stage (1, 2 or 4S; P < 0.001)
      and favourable prognosis (P = 0.044). Better survival probability was shown in
      children with intermediate or high trk-C index compared with patients with low or
      undetectable levels (P = 0.031). All localised tumours co-expressed mRNA for trk
      A and trk-C receptors. RT-PCR analysis detected mRNA encoding the cytoplasmic trk
      C tyrosine kinase region only in favourable neuroblastomas. We conclude that
      favourable neuroblastoma may express the full-length trk-C receptor while
      unfavourable tumours, especially those with MYCN amplification, seem to either
      express no trk-C or truncated trk-C receptors with unknown biological function.
      Trk-C and possibly its preferred ligand NT-3 may be involved in the biology of
      favourable neuroblastomas showing apoptosis or differentiation.

PMID- 9580081
TI  - Application of C18 disks followed by gas chromatography techniques to degradation
      kinetics, stability and monitoring of endosulfan in water.
AB  - A comparative degradation study of endosulfan spiked at 35 micrograms/l in water
      using photocatalysis with (FeCl3/H2O2)/(TiO2/H2O2) and photolysis using either a
      xenon arc lamp and/or sunlight was performed. After irradiation the water samples
      were preconcentrated using C18 solid-phase disk extraction and analysis by gas
      chromatography-electron capture and mass spectrometric detection. Endosulfan
      sulphate was found in the photodegradation studies. Endosulfan showed high
      stability in water when it was exposed to sunlight and xenon are lamp, but by
      means of photocatalysis with FeCl3/H2O2, TiO2/H2O2, the degradation was very fast
      with half lives varying from 59-98 min. The degradation kinetics followed a first
      order reaction and the R.S.D. of rate constants, for n = 3, varied from 4-17%.
      The stability of endosulfan on C18 Empore disks has been determined at 20 degrees
      C, 4 degrees C and -20 degrees C for periods up to 3 months. Endosulfan was not
      degraded on C18 Empore disks. Ground water samples from south of Spain (Almeria)
      were monitored during 1 year. The compounds alpha-, beta- and endosulfan sulphate
      were detected at concentration values varying from 0.5-540 ng/l.

PMID- 9580082
TI  - Arginine vasopressin enhances sympathetic constriction through the V1 vasopressin
      receptor in human saphenous vein.
AB  - BACKGROUND: Arginine vasopressin (AVP) not only acts directly on blood vessels
      through V1 receptor stimulation but also may modulate adrenergic-mediated
      responses in animal experiments in vivo and in vitro. The aim of the present
      study was to investigate whether AVP can contribute to an abnormal adrenergic
      constrictor response of human saphenous veins. METHODS AND RESULTS: Saphenous
      vein rings were obtained from 32 patients undergoing coronary artery bypass
      surgery. The vein rings were suspended in organ bath chambers for isometric
      recording of tension. AVP (3x10[-9] mol/L) enhanced the contractions elicited by
      electrical field stimulation at 1, 2, and 4 Hz (by 80%, 70%, and 60%,
      respectively) and produced a leftward shift of the concentration-response curve
      to norepinephrine (half-maximal effective concentration decreased from 6.87x10[
      7] to 1.04x10[-7] mol/L; P<.05). The V1 vasopressin receptor antagonist
      d(CH2)5Tyr(Me)AVP (10[-6] mol/L) prevented the potentiation evoked by AVP. The
      selective V1 receptor agonist [Phe,2 Orn8]-vasotocin (3x[-10]-9 mol/L) induced
      potentiation of electrical stimulation-evoked responses, which was also inhibited
      in the presence of the V1 receptor antagonist (10[-6] mol/L). In contrast, the V2
      receptor agonist desmopressin (10[-9] to 10[-7] mol/L) did not modify neurogenic
      responses, and the V2 receptor antagonist [d(CH2)5, D-Ile,2 Ile,4 Arg8]
      vasopressin (10[-8] to 10[-6] mol/L) did not prevent the potentiation induced by
      AVP. The dihydropyridine calcium antagonist nifedipine (10[-6] mol/L) did not
      affect the potentiating effect of AVP. CONCLUSIONS: The results suggest that low
      concentrations of AVP facilitate sympathetic neurotransmission and potentiate
      constrictor effects of norepinephrine in human saphenous veins. These effects
      appear to be mediated by V1 receptor stimulation and are independent of calcium
      entry through dihydropyridine calcium channels. Thus, AVP may contribute to
      vascular mechanisms involved in acute ischemic syndromes associated with venous
      grafts, particularly if the sympathetic nervous system is activated.

PMID- 9580083
TI  - Subtotal colectomy vs. intraoperative colonic irrigation in the management of
      obstructed left colon carcinoma.
AB  - PURPOSE: Whether primary anastomosis should be performed after segmental
      resection with intraoperative colonic irrigation or subtotal colectomy is not yet
      established in the surgical treatment of obstructive left colon carcinoma. In
      this prospective, nonrandomized study, we present the results of 66 patients
      undergoing one-stage surgery for obstructed left colon carcinoma. PATIENTS AND
      METHODS: We compared two techniques, subtotal colectomy (35 patients) and
      intraoperative colonic irrigation with segmental resection and immediate
      anastomosis (31 patients). RESULTS: The mortality rate was similar in both
      groups, 8.5 percent in the subtotal colectomy group and 3.2 percent in the
      intraoperative colonic irrigation group. The surgical complication rate was
      significantly higher in the intraoperative colonic irrigation group (41.9
      percent) than in the subtotal colectomy group (14.2 percent; P < 0.05). Mean
      operating time was significantly lower in the subtotal colectomy group than in
      the intraoperative colonic irrigation group (P < 0.05). Both groups had a similar
      mean duration of hospital stay. Ten patients who underwent subtotal colectomy
      (31.2 percent) presented with diarrhea in the immediate postoperative period,
      which disappeared spontaneously or with antidiarrheal medication; a disabling
      diarrhea persisted in two patients only (6.2 percent). CONCLUSION: We believe
      that subtotal colectomy is the treatment of choice for obstructed left-sided
      colonic carcinoma. Segmental resection with intraoperative colonic irrigation is
      more appropriate than subtotal colectomy only in patients with carcinomas of the
      rectosigmoid junction or with previous anal incontinence to avoid the appearance
      of postoperative diarrhea.

PMID- 9580084
TI  - Role of UEV-1A, a homologue of the tumor suppressor protein TSG101, in protection
      from DNA damage.
AB  - The open reading frame YGL087c in the budding yeast Saccharomyces cerevisiae
      genome encodes a polypeptide highly similar to the human UEV (ubiquitin
      conjugating E2 enzyme variant) proteins, which have been proposed to belong to a
      family of putative dominant negative ubiquitin regulators. Deletion of the
      YGL087c open reading frame yields viable cells which are sensitive to UV
      irradiation or methyl methanesulfonate, but not to hydroxyurea. This phenotype is
      reminiscent of that of rad mutants and suggests that the YGL087c-encoded protein
      functions in a process related to tolerance to DNA damage. We also show that the
      mutant phenotype is fully complemented by expression of the human UEV-1A cDNA and
      we propose that UEV-1 proteins could also have a role in protecting higher
      eukaryotic cells from DNA damaging agents.

PMID- 9580085
TI  - "Hard days on the endless frontier" revisited.

PMID- 9580086
TI  - Principles and philosophy of modeling in biomedical research.
AB  - Despite widespread applications in biomedical research, the role of models and
      modeling is often controversial and ill understood. It is usual to find that
      fundamental definitions, axioms, and postulates used in the modeling process have
      become tacit assumptions. What is essential, however, is a clear vision of the
      fundamental principles of modeling. This is even more compelling for new and
      emerging interdisciplinary fields that use techniques from previously separate
      scientific disciplines. This article outlines and reviews the central nature and
      philosophy of modeling, the rules that govern it, and its underlying key integral
      relationship to the 'scientific method'. A comprehensive understanding of these
      issues is indispensable to successful research and meaningful progress in all
      facets of biomedicine.

PMID- 9580088
TI  - De novo smoldering paroxysmal nocturnal hemoglobinuria: a flow cytometric
      diagnosis.
AB  - An asymptomatic 26-year-old woman with mild macrocytic anemia (11.6 g Hb/dl) was
      studied. All biochemical parameters, bone marrow histology and cytogenetics were
      normal. The Ham's and sucrose tests were negative. A flow cytometric analysis
      revealed that CD55 and CD59 staining was absent in 20% and 21% of the
      granulocytes, but erythrocytes and CD34-positive bone marrow cells were CD55 and
      CD59 positive. Seven months after the initial study, the patient suffered an
      episode of hemoglobinuria, with mild anemia, moderate thrombocytopenia and a weak
      positive sucrose lysis test. A new flow cytometric analysis disclosed an
      increased percentage of CD55 and CD59 negative granulocytes and a 25% of
      erythrocytes with an intermediate pattern of fluorescence after CD59 labelling.
      At fourteen months, a population of CD55-deficient erythrocytes was detected and
      the Ham's test became positive. The present report is, to our knowledge, the
      first case of smoldering paroxysmal nocturnal hemoglobinuria in a patient with no
      previous aplastic anemia, or evident pancytopenia. The diagnosis was established
      by flow cytometry of peripheral blood granulocytes, with apparently
      phenotipically normal progenitor cells in an early stage of the disease. Flow
      cytometry appears to be a useful tool in our knowledge of paroxysmal nocturnal
      hemoglobinuria evolution.

PMID- 9580087
TI  - Meropenem versus ceftazidime plus amikacin in the treatment of febrile episodes
      in neutropenic patients: a randomized study.
AB  - BACKGROUND AND OBJECTIVE: Meropenem is the first of a new class of carbapenems
      which may be administered without cilastatin. This study was performed to assess
      the clinical efficacy and tolerability of meropenem monotherapy (1 g/8 h)
      compared with the standard combination of ceftazidime (2 g/8 h) plus amikacin (15
      mg/kg/day) for the empirical treatment of infective febrile episodes in
      neutropenic cancer patients. METHODS: This was a three-center, randomized, non
      blind parallel group trial. The primary objective was to compare the clinical
      efficacy of meropenem monotherapy with that of ceftazidime plus amikacin in the
      empirical treatment of febrile infective episodes in neutropenic patients. This
      was evaluated by the number of patients surviving on unmodified therapy at 72 h
      (primary end point) and by the clinical response at the end of therapy (secondary
      end point). RESULTS: A total of 93 febrile episodes (46 meropenem, 47
      ceftazidime/amikacin) were evaluable. Bone marrow transplant patients accounted
      for 49.5% of all cases. There was a high incidence of Gram-positive infections
      but no pseudomonal infections. Microbiologically documented infections,
      clinically documented infections and unexplained fever accounted for 45%, 10% and
      45% of episodes, respectively. There was a similar proportion of patients in the
      meropenem and ceftazidime/amikacin groups on unmodified empiric therapy at 72 h
      (80.4% vs 76.6%, p = 0.65,) and cured at the end of therapy (37% vs 36.2%, p =
      0.9). No significant difference in tolerability was observed between the groups.
      Meropenem was well tolerated; of note, there were no cases of nausea/vomiting or
      seizure related to its use. INTERPRETATION AND CONCLUSIONS: Meropenem monotherapy
      was well tolerated and produced response rates similar to those obtained with
      ceftazidime/amikacin. The low overall success rates with both treatments concur
      with those of other recent studies and are probably due to a combination of
      several factors, including the adoption of strict assessment criteria.

PMID- 9580089
TI  - Unusual invasive bronchial aspergillosis in a patient with acute lymphoblastic
      leukemia.
AB  - Invasive tracheobronchial aspergillosis is an uncommon form of Aspergillus lung
      infection observed in immunocompromised patients. A 43-year-old patient diagnosed
      with acute lymphoblastic leukemia presented prolonged fever and hemoptysis during
      remission induction chemotherapy. The bronchoscopic examination showed pale
      mucosa with multiple raised white-colored nodules of 3 to 5 millimeters in
      diameter in all the bronchi. Hyphae of Aspergillus sp were observed in the biopsy
      of one of the nodules and in the examination of the bronchoalveolar lavage.
      Despite amphotericin B therapy, the patient developed bilateral necrotizing
      pneumonia and multiple abscesses in the brain and in the thyroid gland, and died.
      From a review of the literature in the Medline database, four similar cases (two
      in AIDS patients, one in lymphoma and the remaining case in an acute myeloid
      leukemia patient) have been reported.

PMID- 9580090
TI  - Interferon-alpha lymphoblastoid in chronic myeloid leukemia patients unresponsive
      to recombinant IFN alpha 2.

PMID- 9580091
TI  - Hypertension in Cuba: evidence of a narrow black-white difference.
AB  - The Caribbean nation of Cuba is comprised of over 10 million persons who trace
      their ancestry primarily to Africa and Spain. To date, little data on blood
      pressure (BP) or hypertension prevalence from Cuba have appeared in English
      language journals. Because the current government has pursued an active policy of
      reducing social differentiation on the basis of ethnic origin, Cuba provides an
      important population laboratory from which to advance the understanding of black
      white differences in BP and hypertension. The authors conducted a population
      based random sample among adults (aged > 15 years) in the city of Cienfuegos.
      Overall response rate was 95%, yielding 1633 participants who provided BP
      readings, self-reported racial group, demographic information, and treatment
      status. Overall prevalence of hypertension (SBP > or = 140 mm Hg or DBP > or = 90
      mm Hg or currently treated) was 44% (46% among blacks and 43% whites; P = 0.19).
      Excess BP among black subjects was reduced slightly by excluding those under
      treatment, but attained statistical significance after adjustment for sex and age
      (P = 0.01). The black-white difference was small, however, relative to that
      observed in the United States. Racial differences in treatment status and control
      were also observed. Although there remains a difference in socioeconomic profile
      between those of African and of European origin in Cuba, this has decreased over
      recent decades. In the United States, the greater magnitude of social
      differentiation parallels a greater relative risk of BP elevation among blacks,
      suggesting that social, economic and psychological factors may play an important
      role in the observed racial gap in cardiovascular risk.

PMID- 9580092
TI  - Effects of 1,10-phenanthroline and hydrogen peroxide in Escherichia coli: lethal
      interaction.
AB  - It has been observed that when Escherichia coli cells are treated simultaneously
      with phenanthroline and H2O2, there is a lethal interaction. In order to analyze
      the mechanism of this lethal interaction, wild-type and xthA mutant cells of E.
      coli were treated with 2.5 mM H2O2 and 1 mM phenanthroline. This treatment was
      preceded by treatments with different metal chelators (dipyridyl for Fe2+,
      desferal for Fe3+ and neocuproine for Cu2+) or conducted simultaneously to other
      treatments with chelators and radical scavengers (thiourea, ethanol and sodium
      benzoate). The lethal interaction was observed in both the E. coli wild-type
      strain and xthA mutant strain, which is deficient in the exonuclease III repair
      enzyme. Nevertheless, the mutant strain was much more sensitive than the wild
      type one. Dipyridyl pretreatment protected the cells against the lethal
      interaction, while desferal pretreament was unable to do so. This suggests that
      the lethal interaction requires Fe2+ and not Fe3+ ions. Ethanol and sodium
      benzoate were incapable of protecting bacterial cells against the lethal
      interaction. Even a 20-min pretreatment with benzoate did not confer protection.
      On the other hand, thiourea protected the cells completely. Based on our results,
      we propose that the lethal interaction may be caused not only by the reaction
      kinetics of phenanthroline and Fe, but also by the ability of phenanthroline to
      intercalate in DNA. After forming the mono and bis complexes, phenanthroline
      would serve as a shuttle and take the Fe2+ ions to the DNA. So, the Fenton
      reaction would take its course with the consequent generation of OH. radicals
      near DNA. This proximity to the DNA would protect the OH. radicals against the
      scavengers' action, thus optimizing the Fenton reaction.

PMID- 9580093
TI  - Comparison between mixed venous oxygen saturation and thermodilution cardiac
      output in monitoring patients with severe heart failure treated with milrinone
      and dobutamine.
AB  - PURPOSE: Although thermodilution cardiac output (COtd) is the accepted method for
      monitoring patients with heart failure in the intensive care unit, it is
      particularly inaccurate in low-flow states and in the presence of tricuspid
      regurgitation; in addition, it does not adequately reflect the interaction
      between oxygen delivery and tissue oxygen extraction. We were concerned about the
      underuse of mixed venous oxygen saturation (SvO2) in this setting and
      hypothesized that it might be a more useful parameter than COtd for evaluating
      hemodynamic status and monitoring therapy in patients with severe congestive
      heart failure. PATIENTS AND METHODS: We determined the correlation coefficients
      between increasing dose of inotrope and each of the parameters COtd and SvO2 in
      18 patients with congestive heart failure who received a 3-day trial of either
      milrinone or dobutamine during admission to the Veterans Affairs Medical Center
      in San Diego. In addition, we analyzed reproducibility of repeated COtd and SvO2
      measurements taken at a single dose of inotrope. RESULTS: In patients receiving
      milrinone the increase in dose correlated much better with SvO2 (average
      correlation coefficient 0.79) than with COtd; this stronger correlation with SvO2
      was seen in 82% of the trials reviewed (p < 0.05). In addition, we found that
      repeated SvO2 measurements taken at a single dose of milrinone were more
      reproducible than COtd as indicated by smaller relative 95% confidence intervals.
      In patients receiving dobutamine no significant trend in correlation coefficients
      or reproducibility was observed. CONCLUSION: The knowledge that there is a
      significant relation between SvO2 and increasing dose of milrinone therapy in
      patients with severe heart failure and tricuspid regurgitation has practical
      value for physicians monitoring these patients in the intensive care unit. We
      believe this study demonstrates the worth of SvO2 in detecting hemodynamic change
      during trials of milrinone therapy and that this parameter may in fact be more
      reproducible than traditional thermodilution methods.

PMID- 9580094
TI  - Role of transesophageal echocardiography in the assessment of patients with blunt
      chest trauma: correlation of echocardiographic findings with the
      electrocardiogram and creatine kinase monoclonal antibody measurements.
AB  - OBJECTIVES: This study was designed to evaluate the usefulness of transesophogeal
      echocardiography (TEE) for detecting cardiac damage after blunt chest trauma
      (BCT). BACKGROUND: Multiple methods have been used to detect cardiac damage after
      a BCT, but none has been demonstrated to be sensitive, specific, and feasible
      enough. METHODS: This multicenter prospective trial was designed to evaluate the
      usefulness of TEE in the assessment of patients with BCT and to compare the TEE
      findings with those provided by the electrocardiogram (ECG) and cardiac
      isoenzymes assay. One hundred seventeen consecutive patients with a significant
      BCT were enrolled. A TEE was performed in each patient. Serial ECGs and plasma
      profiles of creatine kinase (CK) and CK-monoclonal antibody (MB) were obtained.
      RESULTS: Sixty-six (56%) patients had pathologic findings in the TEE attributed
      to the BCT (group A). In the remaining 51 (44%) patients the TEE was normal
      (group B). An abnormal ECG was more frequent in group A (59% vs 24%; p < 0.001),
      and the serum CK-MB peak level was also higher in group A (174 +/- 30 U/L vs 93
      +/- 21 U/L; p = 0.05). Relative to pathologic TEE findings, the sensitivity and
      specificity of an abnormal ECG were 59% and 73% and of high CK-MB with CK-MB/CK >
      5% were 64% and 52%, respectively. CONCLUSIONS: We conclude that TEE can be
      routinely and safely performed for diagnosing cardiac injuries after a BCT and
      plays an important role in the evaluation and treatment of these patients. EGG
      and CK-MB assay are not good methods for detecting cardiac damage in this
      setting.

PMID- 9580095
TI  - Construction and characterization of a stably transformed HeLa cell line in which
      the expression of bovine herpesvirus 1 ICP0 (BICP0) is induced by tetracycline.
AB  - To explore the effects BICP0 (a principal transactivator of BHV-1 gene
      expression) on viral promoter elements, we established a cell line in which the
      expression of BICP0 is regulated by tetracycline. A hybrid promoter containing
      reiterated copies of the tet-operator (tet-O) and a minimal herpesviral alpha
      gene transinducing factor (alpha TIF) responsive element (minimal human
      cytomegalovirus immediate early promoter) was fused to the BICP0 gene and used to
      transform a HeLa cell line which expressed a fusion protein consisting of the
      repressor of the tet-O and the transactivating domain of alpha TIF.
      Simultaneously, the hygromycin resistance gene was transfected to select cells in
      media containing either hygromycin alone or both hygromycin and tetracycline.
      Immunofluorescent assays indicated that BICP0 was synthesised in the transformed
      cell lines solely upon induction of the gene by tetracycline removal. Only cells
      which had been kept constantly in medium containing tetracycline were able to
      synthesise BICP0 upon induction. Induced cell lines transactivated the native
      BICP0 promoter as well as the herpes simplex virus thymidine kinase promoter and
      the long terminal repeat sequences of human immunodeficiency virus in a dose
      dependent manner. These cell lines may help to further explore the functions of
      BICP0 as well as to investigate the molecular basis of interactions between
      herpes- and retroviruses.

PMID- 9580096
TI  - First reported outbreak of abdominal angiostrongyliasis.
AB  - Human abdominal angiostrongyliasis is a potentially fatal disease caused by
      Angiostrongylus costaricensis, a nematode found in the Americas. During the
      period of December 1994 through August 1995, an outbreak of this disease occurred
      in Guatemala. We identified 22 cases of abdominal angiostrongyliasis and
      conducted a matched case-control study to identify risk factors for illness. The
      median age of the 18 cases enrolled in the study was 37 years (range, 9-68
      years), and 11 (61.1%) were male. Consumption of the following six raw food items
      was associated with angiostrongyliasis: mint (odds ratio [OR], 6.9; 95%
      confidence interval [CI], 1.5-66.0), shrimp (OR, infinite; 95% CI, 1.4 to
      infinite), and four kinds of ceviche that reportedly contained raw mint (OR for
      consumption of mint or ceviche that contained mint, 7.0; 95% CI, 1.0-315). We
      conclude that raw mint was the likely vehicle of infection for this outbreak. To
      our knowledge, this is the first reported outbreak of abdominal
      angiostrongyliasis and the first time that a specific food item has been
      epidemiologically linked to the disease.

PMID- 9580097
TI  - The expression of a peroxiredoxin antioxidant gene, AtPer1, in Arabidopsis
      thaliana is seed-specific and related to dormancy.
AB  - We have isolated a gene, AtPer1, from the dicotyledon Arabidopsis thaliana, which
      shows similarity to the 1-cysteine (1-Cys) peroxiredoxin family of antioxidants.
      In higher plants, members of this group of antioxidants have previously only been
      isolated from monocotyledons. It has been suggested that seed peroxiredoxins
      protect tissues from reactive oxygen species during desiccation and early
      imbibition and/or are involved in the maintenance of/protection during dormancy.
      AtPer1 expression is restricted to seeds. Despite differences in seed development
      between monocots and dicots, AtPer1 shows an expression pattern during seed
      development and germination similar to the dormancy-related transcript Per1 in
      barley. In situ hybridization identifies AtPer1 as the first aleurone-expressed
      transcript characterized in developing Arabidopsis seeds. The transcript is also
      expressed in the embryo. AtPer1 expression in seeds is unaltered in an ABA
      deficient mutant (aba-1) during seed development, while expression in seeds of an
      ABA-insensitive mutant (abi3-1) is reduced. The transcript is not induced in
      vegetative tissue in response to stress by ABA or drought. AtPer1 transcript
      levels are correlated to germination frequencies of wildtype seeds, but AtPer1
      transcript abundance is not sufficient for expression of dormancy in non-dormant
      mutants. Hypotheses on peroxiredoxin function are discussed in view of the
      results presented here.

PMID- 9580098
TI  - Dyslipidaemia in female overweight and obese patients. Relation to anthropometric
      and endocrine factors.
AB  - OBJECTIVE: To characterize serum lipid abnormalities in overweight and obese
      female patients and to quantify the relative importance of associated factors.
      METHODS: Cross sectional study at the first visit to the out-patient department.
      237 consecutive overweight and obese female patients (age 31 +/- 14 y, body mass
      index (BMI) 34.2 +/- 6.0 kg/m2) were studied. Evaluation included a questionnaire
      based assessment of dietary and physical activity habits, determination of
      anthropometric indexes (BMI, abdominal/thigh ratio (A/T) and conicity index (CI))
      and endocrine evaluation. Statistical analysis by factorial ANOVA and multiple
      regression. RESULTS: Dyslipidaemia was present in 46% of the patients, with
      hypercholesterolaemia (35%) being more frequent than hypertriglyceridaemia (10%).
      Age but not dietary habits or physical activity patterns was significantly
      related to serum lipid concentrations, independently accounting for 6-10% of
      their variability. Pharmacological drug use resulted in increased serum
      triglyceride concentrations, explaining less than 5% of their variability. Serum
      cholesterol concentrations were not significantly related either to
      anthropometric or to endocrine indexes. For serum triglyceride concentrations,
      anthropometric indexes accounted for 6% of their variability and endocrine
      indexes-postprandial insulin, serum cortisol, testosterone and androstenedione
      together accounted for 32%. CONCLUSION: In mild to moderate female obesity of the
      peripheral type, dyslipidaemia is common. However the most common abnormality,
      hypercholesterolaemia is not significantly related to anthropometric or endocrine
      indexes, while these together account for more than one third of variability in
      serum triglyceride concentrations.

PMID- 9580099
TI  - Thoracic empyema in HIV-infected patients: microbiology, management, and outcome.
AB  - OBJECTIVES: To evaluate etiology, bacteriology, stage of disease, treatment, and
      outcome of HIV-infected patients with thoracic empyema (TE) over a 9-year period
      at a hospital teaching center. DESIGN: We have retrospectively reviewed the
      charts of all HIV-infected patients with a hospital discharge diagnosis of
      empyema between January 1985 and November 1993. PATIENTS: Twenty-three patients
      were identified (22 male and 1 female). The average patient age was 28.7+/-5.3
      years. All the patients were injection-drug users, and 10 (43%) fulfilled
      criteria for an AIDS diagnosis. In 15 cases (65%), the empyema was the first
      cause of medical consultation, which then led to an HIV infection diagnosis in 11
      of them (48%). MEASUREMENTS: In each case, symptoms, chest studies, culture
      results, procedure timing, length of hospitalization, and outcome were reviewed.
      RESULTS: Twenty-one patients (91%) had developed an empyema secondary to
      community-acquired pneumonia. The cultures of pleural fluid were positive in 19
      cases (83%). Anaerobes were isolated from 6 patients and aerobes from 13. A
      single bacteria was isolated from 10 (52%), and multiple organisms (average 2.66
      per case) grew in the remaining 9 positive cultures. The most common organism
      culture growths were Staphylococcus aureus (23%) and Gram-negative bacilli (36%).
      Length of hospitalization averaged 25.6 days (+/-15). Intercostal tube drainage
      was necessary in 18 patients and none required surgery. Patients with AIDS
      diagnosis needed a longer period of hospitalization, and the presence of
      bacteremia and bronchopleural fistula was more frequent. However, this did not
      influence a patient's final outcome. A follow-up was available in 18 cases, with
      4 deaths recorded (average survival, 35 months; range, 4 to 84 months).
      CONCLUSIONS: In our series, TE associated with HIV infection was often the
      primary cause leading to hospital admission and later HIV diagnosis. IV drug
      abuse was the predominant factor for HIV infection and was also related to
      clinical presentation and microbiological findings. The best approach to
      treatment is--as with other patient groups--a prompt drainage and appropriate
      antibiotic treatment, since a favorable outcome is expected.

PMID- 9580100
TI  - Spontaneous regression of a recurrent hepatocellular carcinoma.

PMID- 9580101
TI  - [The medical specialty of endocrinology in the next century, A reflection which
      involves other medical specialties].

PMID- 9580102
TI  - [Isoxsuprine in hypertension during pregnancy].
AB  - The objective of this paper is to demonstrate that isoxsuprine is an effective,
      quick hypotensive of easy management in the hypertension of pregnancy that does
      not have adverse effects on the mother-fetus binomial. This study was carried out
      at the Obstetric Intensive Care Unit at the Gyneco-Obstretrics Hospital in the
      Centro Medico Nacional La Raza of the IMSS. Fifty patients were chosen and
      managed according to the protocol management of the hospital; they had a
      diagnosis of severe toxemia or preeclampsia in patients with 24 weeks or more of
      pregnancy, with hypertension, edema, convulsions and/or coma state or without
      concomitant or previous pathological states. All of the patients received
      isoxsuprine (50 mg in 250 ml of DW5%). We evaluated the hypotensive effect of
      isoxsuprine according to the time and average dose administered, and its effect
      on the mother and fetus heart frequency according to the basal values. We valued
      the APGAR score at minute one and minute five, seconds after the delivery. We
      analyzed according to the degrees of toxemia and at the end of the obstetric
      event. We demonstrated a significant decrease in the arterial tension after
      administration fifteen minutes later with a dose of nine drops (0.29 mcg/min)
      average and demonstrated at the same time that there are no adverse effects on
      the mother fetus binomial. Isoxsuprine is an affective, quick and economical
      hypotensive of easy management that has no adverse effects on mother-fetus
      glycemia, obstetric bleeding and APGAR score.

PMID- 9580103
TI  - [Skin lesions in a 1,000 newborns. A case and control study].
AB  - Cutaneous alterations are common in neonates. Nevertheless, no reliable studies
      exist to characterize the type and frequency of skin diseases in Mexican
      newborns. We carried out a prospective study for 6 month on 1,000 children to
      analyze cutaneous lesions present during the neonatal period in our population.
      Of these children, 790 (78%) were neonates admitted to the well-baby nursery, and
      220 (22%) were in the sick-baby nursery. Comparison was made between the two
      groups. It was found that all the newborns (100%) from both groups presented from
      2 to 10 different cutaneous lesion. A wide variety of skin diseases were found,
      but most were of a transitory nature. Birthmarks were less common and
      malformations even more so. By means of the X2 method, there was no statistically
      significant difference between the two groups (p > 0.1).

PMID- 9580104
TI  - [Prevalence of non insulin dependent diabetes mellitus and associated risk
      factors in the Mazatec population of the State of Oaxaca, Mexico].
AB  - The occurrence non-insulin dependent diabetes mellitus has increased during the
      second half of this century in Mexico as well as in other countries. American
      Indians have one of the highest prevalences in the world, but there are few
      studies that have estimated the occurrence of diabetes in Mexican Indians. The
      authors conducted a cross-sectional study in Huautla, Oaxaca, Mexico, to estimate
      the prevalence of diabetes in Mexican Mazatecos Indians, as well as its related
      risk factors. A total of 798 subjects were interviewed, and 16 diabetics were
      found, the prevalence of diabetes was 2.01%. The prevalence increased with age,
      but declined in those 65 years of age or older, mainly in women. The prevalence
      was slightly higher in women (2.2%) than in men (1.6%). There was a relation of
      diabetes with obesity, central body fat distribution, a family history of
      diabetes and hypertension. The prevalence is low if compared with the notified
      prevalence in the country, but there are certain age groups where its occurrence
      is similar to those living in an urban area. There is a need of intervention
      measures to prevent an epidemic such as the one seen nowadays among American
      Indians.

PMID- 9580105
TI  - [Therapeutic and diagnostic uses of cells and tissues cultured in vitro].

PMID- 9580106
TI  - [Molecular epidemiology of high-incidence cancers in Mexico].

PMID- 9580107
TI  - [International Workshop on Molecular Epidemiology. Proposals of the
      Interdisciplinary Group on American Trypanosomiasis and Leishmaniasis].
AB  - Parasite diseases such as Leishmaniases and American Trypanosomiases have been
      increasingly important in Mexico and other countries of the American Region. In
      known areas, these diseases are highly endemic, and in recently opened developing
      areas became a new threat to public health. Some social groups working in natural
      resources exploitation, agriculture, animal stock and public labor are
      particularly affected. The molecular epidemiology approach to these diseases is
      linking valuable capabilities and resources within the academic and operational
      institutions actual working in genetic polymorphism, strain characterization and
      PRC identification of Trypanosoma and Leishmania parasites. Clinical and
      epidemiological aspects of American trypanosomiasis infections and Chagas's
      disease and of cutaneous, mucocutaneous, disseminated and visceral leishmaniases,
      as well as genetic susceptibility studies have been initiated by Mexican
      scientists. In order to organize and coordinate the molecular epidemiology
      activities and support effective prevention and control programs against these
      diseases, political decision from the health, and academic authorities is
      urgently needed to adopt and support the research strategy for typing Trypanosoma
      and Leishmania species through exposition and biological markers (analysis of
      chromosomal DNA, ribosomal genes restriction patterns, DNA sequence, and DNA
      plasmids); the study of the membrane proteins and isoenzymes and monoclonal
      antibodies; detecting antigens and nucleic acids; defining susceptibility to
      infection with genetic markers, and searching for species, variants and mutant
      strains responsible for high virulence. The support for the establishment of a
      Reference Center for identification, cryopreservation and registration of
      parasites, vectors and reservoires is of paramount importance.

PMID- 9580108
TI  - Subclasses of IgG in different aged rats with fasciolosis.
AB  - The variations in antibody responses (total IgG and IgG1, IgG2a, IgG2b, and IgG2c
      subclasses) were studied in two groups of rats infected with metacercariae of the
      trematode Fasciola hepatica L. Animals of group 1 were 4 weeks old, and rats of
      group 2 were 13 weeks old. All IgG subclasses increased during the course of
      infection except IgG2c, which decreased. The younger rats reached more marked
      responses than the older, at least during the period of this trial. IgG1 and
      IgG2a antibodies reached the highest levels, and among these two, IgG2a response
      was slightly superior to IgG1.

PMID- 9580109
TI  - Molecular genetic analysis of patients carrying steroid 21-hydroxylase deficiency
      in the Mexican population: identification of possible new mutations and high
      prevalence of apparent germ-line mutations.
AB  - Steroid 21-hydroxylase deficiency is the underlying cause in over 90% of patients
      with congenital adrenal hyperplasia, an inherited metabolic disorder of adrenal
      steroidogenesis. We have characterized 94 mutant alleles from 47 unrelated
      Mexican patients and the corresponding mutant alleles in their parents by
      amplification of the functional CYP21 gene by PCR, followed by direct sequence
      analysis. The study included patients diagnosed with the three clinical forms of
      the disease. Our results revealed: (1) the presence of relatively few mutations
      or combinations of mutations associated with particular phenotypes; (2) the
      presence of putative new mutations; (3) the finding of identical genotypes in
      patients displaying discordant phenotypes; (4) the identification of patients
      lacking all previous reported mutations; and (5) an apparent high frequency of
      germ-line mutations. The absence of previously reported mutations in about 22% of
      the disease alleles, the finding of putative new mutations in some of the
      patients lacking previously known mutations, and the apparent high prevalence of
      germ-line mutations make evident the differences in the genetic background
      leading to this disorder between the Caucasian and the Mexican populations.

PMID- 9580110
TI  - Human apolipoprotein A-II is a pro-atherogenic molecule when it is expressed in
      transgenic mice at a level similar to that in humans: evidence of a potentially
      relevant species-specific interaction with diet.
AB  - We report on the effect of human apolipoprotein (apo) A-II transgene expression
      on atherosclerosis susceptibility in two transgenic lines (25.3 and 11.1) whose
      plasma human apoA-II concentrations (approximately 23 and 96 mg/dl, respectively)
      span the normal range in humans. After 9 months of an atherogenic diet, 25.3 and
      11.1 transgenic mice developed aortic atherosclerotic lesions that were
      approximately 1.7- and 7-fold, respectively, more extensive than those of non
      transgenic control mice. However, there was no difference in the area of
      atherosclerosis of transgenic and control mice when fed a regular chow diet This
      contrasts with the findings in murine apoA-II transgenic mice and provides
      evidence of a species-specific characteristic that could be of relevance with
      respect to the high fat intake diets common in most industrialized countries. A
      possible mechanism of the pro-atherogenic action of human apoA-II could be the
      inhibition of reverse cholesterol transport and, in support of this, we observed
      an impairment of apoA-I-HDL particle interconversion in the plasma of 11.1
      transgenic mice caused, at least in part, by a marked decrease in the endogenous
      lecithin:cholesterol acyltransferase activity.

PMID- 9580111
TI  - Melatonin interaction with magnesium and zinc in the response of the striatum to
      sensorimotor cortical stimulation in the rat.
AB  - The sensorimotor cortex (SMCx) sends numerous projections to the striatum. These
      projections are excitatory and glutamate mediated. Glutamatergic receptors,
      specifically those of NMDA type-receptors, are closely related to excitotoxicity.
      Thus, in some circumstances, an excess of Ca2+ influx through NMDA channels
      alters neuronal metabolism and may become lethal for the cell. Two other divalent
      cations, Mg2+ and Zn2+, have inhibitory effects on NMDA receptors. Magnesium ions
      exert a voltage-dependent block of the NMDA calcium channel, whereas zinc ions
      exert a voltage-independent NMDA block. In the present work, the effects of
      iontophoresis of Mg2+ and Zn2+ on the striatal response to SMCx stimulation were
      studied. Moreover melatonin, an indoleamine with anticonvulsant properties and
      inhibitory effects on the NMDA receptor, was also iontophorized alone or in
      combination with Mg2+ and Zn2+. Single pulse electrical stimulation of SMCx
      produced an excitatory response in the striatum. Iontophoresis of melatonin, Mg2+
      and Zn2+ produced a potent attenuation of the excitatory response of the striatum
      to SMCx stimulation, although the latency of the effect of melatonin was longer
      than those of Mg2+ and Zn2+. When these cations were simultaneously ejected with
      melatonin, additive inhibitory effects were recorded. These observations suggest
      that the inhibitory effects produced by Mg2+ and Zn2+ and melatonin are produced
      via different processes, and thus the inhibitory role of melatonin on the NMDA
      receptor activity is exclusive of a direct action on the NMDA calcium channel.

PMID- 9580112
TI  - EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by
      Bcl-XL.
AB  - Signaling through the epidermal growth factor receptor (EGFR) has been primarily
      implicated in the growth of epithelial cells including keratinocytes. However,
      the mechanism by which EGFR stimulation promotes keratinocyte cell growth is
      poorly understood. Here we report that human keratinocytes undergo apoptosis when
      incubated with the blocking EGFR monoclonal antibody 225 IgG, or PD153035, a
      highly specific EGFR tyrosine kinase inhibitor. Endogenous mRNA and protein
      levels of Bcl-XL, a member the Bcl-2 family which suppresses apoptosis, were
      specifically inhibited by EGFR blockade. Furthermore, stimulation of EGFR
      signaling through two natural ligands, transforming growth factor (TGF)-alpha and
      epidermal growth factor (EGF), increased the expression of Bcl-XL in quiescent
      keratinocytes and HaCaT cells. Finally, ectopic expression of Bcl-XL in HaCaT
      cells increased survival after EGFR blockade when compared to untransfected cells
      or HaCaT keratinocytes transfected with empty vector. These results suggest that
      the anti-apoptotic protein Bcl-XL plays an important role in the maintenance of
      keratinocyte survival in response to EGFR signaling.

PMID- 9580113
TI  - Educational outcomes of an otitis media workshop for primary care providers in
      Latin America.
AB  - Otitis media is a prevalent condition that can be diagnosed and treated by
      primary care providers skilled in otoscopy. Previous analysis demonstrated that
      brief, intensive instruction at one site in rural Mexico improved the test scores
      of health care providers and changed long-term practices (Eavey R, et al.
      Otolaryngol Head Neck Surg 1993; 109:895-8). We wanted to confirm these test
      score findings at other sites. A didactic course on otitis media with a practical
      otoscopy workshop was conducted at six Mexican locations and in one Venezuelan
      city by an interdisciplinary group of physicians. The same coded test was given
      immediately before and after the course. The Wilcoxon test for significance of
      intrasubject performance before and after intervention was used as a
      nonparametric assessment. At all seven sites (n = 190 subjects), test scores
      demonstrated statistically significant improvement (range = p < 0.001 to p <
      0.0001). We conclude that this educational method consistently improved short
      term knowledge of otitis media and that further teaching efforts and a longer
      term practice-impact study are warranted.

PMID- 9580114
TI  - [Cajal and the Regenerationist movement].

PMID- 9580115
TI  - Low probability of transmission of Trypanosoma cruzi to humans by domiciliary
      Triatoma sordida in Bolivia.
AB  - The role of Triatoma sordida in the domestic transmission of Trypanosoma cruzi
      was assessed in 7 rural localities in Velasco Province, Department of Santa Cruz,
      Bolivia. Tri. sordida, the only triatomine species identified in these
      localities, was found inside 58.0% of houses but not in large numbers (3.1 bugs
      per infested house on average). A total of 220 faecal samples from domiciliary
      bugs was examined microscopically and by the polymerase chain reaction for the
      presence of trypanosomes: 21.4% were infected. Analysis of blood meals of
      domiciliary Tri. sordida showed that humans were the commonest host (70.4%),
      followed by chickens and dogs. Four of 418 persons tested were seropositive for
      Tryp. cruzi. Only 2 of a second group of 62 persons living in dwellings infested
      by Tri. sordida were seropositive. Tryp. cruzi infection was demonstrated in dogs
      and domestic rats. Three other species of small mammals were found to be infected
      with trypanosomes. In our study area, domestic Tri. sordida are mainly
      incriminated in the transmission of Tryp. cruzi to synanthropic animals, whereas
      transmission to humans is very rare. The presence in houses of small populations
      of Tri. sordida infected with Tryp. cruzi is therefore currently insufficient for
      this insect to constitute a major epidemiological risk factor.

PMID- 9580116
TI  - Recombinant antigens for specific and sensitive serodiagnosis of Latin American
      tegumentary leishmaniasis.
AB  - The diagnostic potential of recombinant leishmanial antigens for Latin American
      tegumentary leishmaniasis (LATL) was examined. Two Leishmania (Viannia) peruviana
      recombinant proteins, T26-U2 and T26-U4, were assessed by their reactivity to
      detect specific anti-leishmanial antibodies. Seventy-eight individual sera from
      persons with LATL, 39 from those with other diseases, and 10 negative control
      sera were tested by Western blotting and enzyme-linked immunosorbent assay. The
      sensitivity of the test using T26-U2 plus T26-U4 was similar to that obtained
      with whole parasite extract (92%). However, the specificity obtained using both
      recombinant antigens (87%) was higher than that of the whole parasite extract
      (65%). All tests using recombinant proteins (T26-U2, T26-U2 plus T26-U4 or T26
      U4) had a higher positive predictive value (89%, 92% and 98%, respectively) than
      the value obtained using total parasites (81%). Eleven Colombian sera were also
      tested, and the results indicated that T26-U2 plus T26-U4 could be used
      successfully in Peru and in other Latin American countries.

PMID- 9580117
TI  - Nitazoxanide for the treatment of intestinal protozoan and helminthic infections
      in Mexico.
AB  - A study to evaluate the efficacy and safety of nitazoxanide as a single agent for
      the treatment of a broad spectrum of mixed parasitic infections, both protozoa
      and helminths, was conducted at a primary school in San Pedro Toliman, Queretaro,
      Mexico. Three faecal samples from 1824 adults and children were screened for the
      presence of oocysts, cysts, trophozoites, eggs or larvae of intestinal protozoa
      or helminths. Two hundred and forty-six adults and children infected with at
      least one protozoan and 2 helminths were given 7.5 mg/kg of nitazoxanide (500 mg
      to adults and 200 mg to children less than 12 years old) every 12 h for 3
      consecutive days. Faecal samples were examined on days 6, 7, 8, 13, 14 and 15 (+/
      1) following initiation of treatment, using formalin-ether concentration and
      Kato-Katz egg counting. Treatment with nitazoxanide was 71-100% effective in
      eliminating evidence of infection with Entamoeba histolytica/E. dispar, Giardia
      duodenalis, Blastocystis hominis, Isospora belli, Enterobius vermicularis,
      Ascaris lumbricoides, Trichuris trichiura and Hymenolepis nana. Haematology and
      clinical chemistry values obtained before and after treatment remained unaffected
      by nitazoxanide. The drug was well tolerated, with only 15 patients (6.1%)
      reporting mild abdominal pain that lasted less than 24 h.

PMID- 9580118
TI  - Functional glomerular reserve in recipients of en bloc pediatric transplant
      kidneys.
AB  - BACKGROUND: The transplantation of an adequate renal mass is increasingly
      recognized to be of importance. The improved graft survival is probably due to a
      lesser risk of developing hyperfiltration-associated lesions. METHODS: We have
      reviewed the glomerular reserve in our recipients of en bloc pediatric transplant
      kidneys after an intravenous amino acid overload and compared them to single
      adult kidney transplant recipients. RESULTS: En bloc transplants evidenced
      increased glomerular filtration rate as compared with baseline as from the second
      hour of amino acid infusion (from 71+/-14 to 84.9+/-17 ml/min, 1.73 m2, P<0.05)
      and increased renal plasma flow as from the third hour (from 335+/-116 to 402+/
      155 ml/min, 1.73 m2, P<0.05). In the single adult kidney recipient group, no
      change was seen either in the glomerular filtration rate (from 62.5+/-13 to
      58.1+/-13 ml/min, 1.73 m2, P=NS) nor in renal plasma flow (from 354+/-125 to
      304+/-98 ml/min, 1.73 m2, P=NS). CONCLUSIONS: These results show that patients
      receiving en bloc pediatric kidney transplantations have a greater renal
      functional reserve and show a lesser risk of hyperfiltration.

PMID- 9580119
TI  - Right coronary artery arising from the left aortic sinus in a heart with left
      coronary dominance: a post-mortem description--a case report.
AB  - The authors report the post-mortem description of the coronary arterial
      circulation of an 81-year-old man. The heart showed a concordant atrioventricular
      and ventricle-arterial disposition. The coronary artery distribution presented
      left dominance. No myocardial scars were observed. The ostium of the right
      coronary artery (RCA) was located in the left aortic sinus just in front of the
      opening of the left coronary artery. The ostium was slit-like and its maximum
      diameter was 5 mm. The RCA began between the aorta and the pulmonary trunk and
      ended as a small right marginal artery. The absence of heart disease and the
      man's survival until an advanced age were probably due to the fact that the RCA
      supplied only a small portion of the right ventricle, given the left coronary
      dominance.

PMID- 9580121
TI  - Automated segmentation of cell nuclei in fine needle aspirates of the breast.
AB  - OBJECTIVE: To achieve a classifier of breast lesions to discriminate between
      benign and malignant cases of cytologic smears with automated segmentation image
      analysis techniques. STUDY DESIGN: The techniques were applied to images of
      epithelial cell nuclei from cytologic smears obtained by fine needle aspiration.
      The images of the nuclei were taken from 95 cases of malignant lesions and 47
      benign (approximately 25 nuclei per case), and 28 nuclear variables were
      measured. The data were analyzed by a double methodology, discriminant analysis
      and classification and regression trees (CART), to determine which provided the
      best results. RESULTS: CART selected the SD of the nuclear area with correct
      classification of 85.1% of benign and 94.7% malignant aspirates. Discriminant
      analysis selected the group of variables formed by axis lengths, SD of the
      longest axis, sphericity and variance of gray levels, with results similar to
      those of CART. CONCLUSION: Automated segmentation image analysis techniques were
      effective, and the classifier was quick, simple and efficacious in malignant
      benign discrimination.

PMID- 9580120
TI  - Phacomatosis pigmentokeratotica: report of new cases and further delineation of
      the syndrome.
AB  - BACKGROUND: The epidermal nevus syndromes include different diseases that have
      the common feature of mosaicism. One of these has been recently identified and
      named phacomatosis pigmentokeratotica, in analogy to phacomatosis
      pigmentovascularis. It is characterized by an organoid nevus with sebaceous
      differentiation, a speckled-lentiginous nevus, and other associated anomalies. It
      has been hypothesized that this syndrome is caused by a particular genetic
      mechanism known as the twin-spot phenomenon. OBSERVATIONS: We describe 3 patients
      manifesting an association of organoid nevus showing sebaceous differentiation
      and speckled-lentiginous nevus with associated anomalies and update the
      neurologic findings of a previously described patient. Hemiatrophy seems to be a
      common finding in all cases; hyperpathia, dysesthesia, and hyperhidrosis, as well
      as other neurologic defects, may be present. CONCLUSIONS: The findings in these
      patients allowed us to better delineate this syndrome. Further studies are needed
      to elucidate the underlying genetic defect. At present, however, the hypothesis
      that best explains this phenotype is twin spotting. Clinical recognition of this
      syndrome can contribute to the classification of the epidermal nevus syndromes
      and give insight into unusual genetic mechanisms occurring in humans.

PMID- 9580122
TI  - Synthesis and in vitro anthelmintic activity against Nippostrongylus brasiliensis
      of new 2-amino-4-hydroxy-delta-valerolactam derivatives.
AB  - The synthesis of a series of 2-amino-4-hydroxy-delta-valerolactam derivatives is
      described (compounds 4 to 10). These compounds showed a high anthelmintic in
      vitro activity against the Nippostrongylus brasiliensis model.

PMID- 9580123
TI  - [Hemorrhage induced by snake venoms in Argentina].
AB  - Mice of 18 and 20 g were injected intradermally with 0.1 ml of serial dilution of
      venom in saline solution 0.9 buffered pH 7.2. Groups of 4 animal were formed,
      they were sacrificed 2 hours after inoculation. Skin of every mouse was put out,
      and the haemorrhagic area was measured Bothrops alternatus, Bothrops jararaca,
      Bothrops jararacussu and bothrops neuwiedii venoms were used. Crotalus durissus
      terrificus did not show any haemorrhagic activity.

PMID- 9580124
TI  - Extension of a Jovanovic-Freundlich isotherm model to multicomponent adsorption
      on heterogeneous surfaces.
AB  - A recently proposed Jovanovic-Freundlich isotherm model for single component
      adsorption without lateral interactions on heterogeneous surfaces is extended to
      account for lateral interactions and for competitive adsorption. The model is
      tested using previously reported single component and competitive adsorption data
      of 2-phenylethanol and 3-phenylpropanol on ODS-silica with methanol-water as the
      mobile phase. A comparison is made regarding the ability of the Jovanovic
      Freundlich and Langmuir-Freundlich models to predict competitive equilibria using
      the single component identified parameters. Fair predictions of the competitive
      data were obtained when using heterogeneous-surface models which do not take into
      account the possible interactions of phenylalcohols in the adsorbed phase via
      hydrogen bonding. Markedly improved predictions were obtained with models which
      account simultaneously for the two main sources of adsorbed phase nonideal
      behavior, i.e. adsorbate-adsorbate interactions and heterogeneity of the
      adsorbent surface.

PMID- 9580125
TI  - Synaptonemal complex analysis of the X1X2Y trivalent in Mantis religiosa L.
      males: inferences on the origin and maintenance of the sex-determining mechanism.
AB  - Characterization of sex chromosomes in males of Mantis religiosa L. (2n = 24 +
      X1X2Y) was carried out by C-banding, silver staining and fluorescence in situ
      hybridization. They are meta- or submetacentric, their arms being designated as
      X1L, X1R, X2R, X2L, YL and YR. Meiotic behaviour of the sex trivalent was
      examined through the analysis of synaptonemal complexes (SCs), prometaphase I
      (metaphase I) and metaphase II nuclei. On the basis of the SC analysis,
      chromosomal length measurements at mitosis and prometaphase I and data from
      several orthopteran species, it is proposed that the breakpoints of the
      reciprocal translocation that originated this complex sex-determining mechanism
      were close to the centromeres of the X and the largest autosome, and that the
      asynapsed X1L and X2R regions observed in the sex trivalent at pachytene
      represent the original X chromosome. The X centromere being probably that of the
      X2 element because it lacks a partner in the SC pachytene trivalent. The
      relationship among synaptic pattern, chiasma localization and balanced
      segregation of the sex trivalent is also discussed.

PMID- 9580126
TI  - Pre-IDDM and preventive trials without placebo controls.

PMID- 9580127
TI  - Pyridazine derivatives XIV. Study of the vasorelaxant action of 6-aryl-5
      piperidino-3-hydrazinopyridazines in isolated rat thoracic aorta: comparison with
      hydralazine.
AB  - 1. For several years we have been working on the synthesis of modified
      hydrazinopyridazines which have proved to possess remarkable vasorelaxant and
      antihypertensive activity. We now report the vasodilator effects of three novel 6
      aryl-5-piperidino-3-hydrazinopyridazines (1a, 1b and 1c), structurally related to
      the well-known antihypertensive drug hydralazine. 2. Hydralazine and the new
      hydrazinopyridazines relaxed, in a concentration-dependent and nonspecific way,
      the contractions elicited by noradrenaline or a high K+ concentration in rat
      aortic rings with or without endothelium. According to the IC50 (50% inhibitory
      concentrations) values obtained, the vasorelaxant potency of the new compounds
      was greater than that of hydralazine. 3. In a Ca2+-free medium, the contractions
      provoked by noradrenaline or caffeine were significantly inhibited by the new
      hydrazinopyridazines and by hydralazine. 4. Hydralazine and the novel molecules
      did not significantly modify basal, noradrenaline- or K+-induced 45Ca2+ uptake.
      5. These results suggest that 1a, 1b and 1c have an endothelium-independent
      vasorelaxant activity greater than that of hydralazine in isolated rat aortic
      rings, which seems not to be mediated by a blockade of transmembrane Ca2+
      movements through specific channels. This effect could be due, at least in part,
      to an intracellular mechanism of action.

PMID- 9580128
TI  - Catalepsy induced by nitric oxide synthase inhibitors.
AB  - 1. Previous study showed that N(G)-nitro-L-arginine (L-NOARG), an inhibitor of
      nitric bxide synthase, induces catalepsy in a dose-dependent manner in male
      albino-Swiss mice. 2. The objective of the present work was to further
      investigate this effect, extending it to other NOS inhibitors. 3. Results showed
      that L-NOARG (40-80 mg/kg i.p.), N(G)-nitro-L-arginine methylester (L-NAME, 40
      160 mg/kg i.p.) or N(G)-monomethyl-L-arginine (L-NMMA, 80 mg/kg i.p.) were able
      to induce catalepsy in mice. The effect of L-NOARG (40 mg/kg) was antagonized by
      pretreatment with L-arginine (300 mg/kg), but not by D-arginine (300 mg/kg). The
      catalepsy-inducing effect of L-NOARG suffered rapid tolerance, showing a
      significant decrease after two days of chronic treatment (40 mg/kg i.p., twice a
      day). 4. The results suggest that interference with the formation of nitric oxide
      induces significant motor effects in mice.

PMID- 9580129
TI  - Role of cyclic guanosine monophosphate and K+ channels as mediators of the
      mesenteric vascular hyporesponsiveness in portal hypertensive rats.
AB  - The mechanisms mediating the hyporesponsiveness to vasoconstrictors in portal
      hypertension are not completely established. In the present study, we evaluated
      the role of cyclic guanosine monophosphate (cGMP) and potassium channels as
      contributors to the pressor hyporesponsiveness to methoxamine (MTX) of the
      mesenteric vascular bed of portal vein-ligated (PVL) hypertensive rats. In basal
      conditions, and compared with sham-operated control rat (SHAM) vessels, PVL
      preparations showed a blunted pressor response (maximum: 39.3 +/- 6.1 vs. 94.5 +/
      8.9 mm Hg), which increased by pretreatment with methylene blue (MB), a
      guanylate cyclase inhibitor (118.7 +/- 8.9 vs. 152.0 +/- 10.0, respectively), and
      even more with the nitric oxide (NO) synthesis inhibitor N(omega)-nitro-L
      arginine (NNA) (159.9 +/- 7.4 vs. 194.1 +/- 5.7, respectively), suggesting that
      NO acts through cGMP-dependent and independent mechanisms. In all cases, however,
      the pressor responses of PVL vessels were lower than those of SHAM. Pretreatment
      of the vessels with the potassium channel inhibitors, tetraethylammonium (TEA),
      glibenclamide (GLB), or charybdotoxin (CHX), did not improve the reduced pressor
      responses of the PVL rats. However, when the preparations were simultaneously
      pretreated with MB and TEA or with NNA and TEA, the pressor responses were
      potentiated with respect to groups treated with MB or NNA alone, and the
      differences between PVL and SHAM vessels were completely corrected. These data
      suggest that both NO and potassium channels mediate the vascular
      hyporesponsiveness to methoxamine of the PVL mesenteric vasculature. Our results
      also disclose that NO blunts the pressor response of the PVL vessels by a dual
      mechanism of action, through activation of potassium channels and through the
      formation of cGMP. Finally, the NO-independent component mediated by potassium
      channels can be only seen when the main cGMP-NO component is inactivated. In
      conclusion, both cGMP and potassium channels mediate the vascular
      hyporesponsiveness to MTX of the mesenteric bed of portal hypertensive rats.

PMID- 9580130
TI  - Two marine Agrobacterium producers of sesbanimide antibiotics.
AB  - Sesbanimides are cytotoxic compounds, originally isolated in 1983 from seeds of
      the leguminous plants Sesbania drummondii and Sesbania punicea. In this paper we
      describe the bacterial production of sesbanimides by two "marine Agrobacterium";
      strain PH-103 which produces Sesbanimide-A and strain PH-A034C which produces
      Sesbanimide-C. The isolation and taxonomy of the producing microorganisms,
      fermentation and isolation of sesbanimides are reported.

PMID- 9580131
TI  - Characterization of IS1515, a functional insertion sequence in Streptococcus
      pneumoniae.
AB  - We describe the characterization of a new insertion sequence, IS1515, identified
      in the genome of Streptococcus pneumoniae I41R, an unencapsulated mutant isolated
      many years ago (R. Austrian, H. P. Bernheimer, E. E. B. Smith, and G. T. Mills,
      J. Exp. Med. 110:585-602, 1959). A copy of this element located in the cap1EI41R
      gene was sequenced. The 871-bp-long IS1515 element possesses 12-bp perfect
      inverted repeats and generates a 3-bp target duplication upon insertion. The IS
      encodes a protein of 271 amino acid residues similar to the putative transposases
      of other insertion sequences, namely IS1381 from S. pneumoniae, ISL2 from
      Lactobacillus helveticus, IS702 from the cyanobacterium Calothrix sp. strain PCC
      7601, and IS112 from Streptomyces albus G. IS1515 appears to be present in the
      genome of most type 1 pneumococci in a maximum of 13 copies, although it has also
      been found in the chromosome of pneumococcal isolates belonging to other
      serotypes. We have found that the unencapsulated phenotype of strain 141R is the
      result of both the presence of an IS1515 copy and a frameshift mutation in the
      cap1EI41R gene. Precise excision of the IS was observed in the type 1
      encapsulated transformants isolated in experiments designed to repair the
      frameshift. These results reveal that IS1515 behaves quite differently from other
      previously described pneumococcal insertion sequences. Several copies of IS1515
      were also able to excise and move to another locations in the chromosome of S.
      pneumoniae. To our knowledge, this is the first report of a functional IS in
      pneumococcus.

PMID- 9580132
TI  - Identification of a novel nonsense mutation and a missense substitution in the
      vasopressin-neurophysin II gene in two Spanish kindreds with familial
      neurohypophyseal diabetes insipidus.
AB  - Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant
      disease caused by deficiency in the antidiuretic hormone arginine vasopressin
      (AVP) encoded by the AVP-neurophysin II (AVP-NPII) gene on chromosome 20p13. In
      this study, we analyzed two families with FNDI using direct automated
      fluorescent, solid phase, single-stranded DNA sequencing of PCR-amplified AVP
      NPII DNA. In one of the families, affected individuals presented a novel nonsense
      mutation in exon 3 of the gene, consisting in a G to T transition at nucleotide
      2101, which produces a stop signal in codon 82 (Glu) of NPII. The premature
      termination eliminates part of the C-terminal domain of NPII, including a
      cysteine residue in position 85, which could be involved in the correct folding
      of the prohormone. In the second family, a G279A substitution at position -1 of
      the signal peptide was observed in all affected individuals. This missense
      mutation, which replaces Ala with Thr, is frequent among FNDI patients and is
      thought to reduce the efficiency of cleavage by signal peptidases.

PMID- 9580133
TI  - Necrotizing external otitis caused by Aspergillus fumigatus: computed tomography
      and high resolution magnetic resonance imaging in an AIDS patient.
AB  - Most necrotizing (malignant) external otitis (NEO) occurs in diabetic patients
      and is commonly caused by Pseudomonas aeruginosa. We report an acquired
      immunodeficiency syndrome (AIDS) patient with NEO caused by Aspergillus fumigatus
      in which computed tomography (CT) showed destructive petrous bone involvement and
      magnetic resonance imaging (MRI) of the ear discovered extensive soft tissue and
      facial nerve involvement. Dedicated MRI studies of the ear in this type of
      pathology provide new insights relating to nerve dysfunction, that cannot be
      obtained with CT.

PMID- 9580134
TI  - Managed care, professional integrity, and ethics.

PMID- 9580135
TI  - Oral angiosarcoma misdiagnosed as a pyogenic granuloma.

PMID- 9580136
TI  - Persistent idiopathic unilateral hypoglossal nerve palsy.

PMID- 9580137
TI  - Aortopulmonary paraganglioma: an overview after five years.

PMID- 9580138
TI  - Secondary hyperparathyroidism: detection with I-123-Tc-99m-Sestamibi subtraction
      scintigraphy versus US.
AB  - PURPOSE: To compare iodine-123-technetium-99m-sestamibi subtraction scintigraphy
      with ultrasonography (US) for detection of parathyroid abnormalities in uremic
      patients with secondary hyperparathyroidism. MATERIALS AND METHODS: Fourteen
      adult uremic patients with severe secondary hyperparathyroidism underwent
      subtraction scintigraphy before total or subtotal parathyroidectomy. Subtraction
      scintigrams were acquired with a double-energy-window technique. US was performed
      with high-frequency transducers and standard methods. RESULTS: 1-123-Tc-99m
      sestamibi subtraction scintigraphy correctly demonstrated 41 of 50 surgically
      confirmed enlarged parathyroids; US demonstrated 27. Sensitivity for detection of
      hyperplastic glands was 82% for scintigraphy and 54% for US. Scintigrams were
      correct in seven patients, and US scans were correct in five. Scintigraphy
      demonstrated all four enlarged parathyroids in six of 12 patients who were to
      undergo first surgery, whereas US demonstrated all four enlarged glands in three
      of the 12 patients. Gland weight was correlated with likelihood of detection with
      either method. Glands undetected at scintigraphy were significantly (P < .01)
      smaller (mean weight, 257 mg) than those undetected at US (mean weight, 467 mg).
      CONCLUSION: I-123-Tc-99m-sestamibi subtraction scintigraphy is efficient for
      detection of enlarged parathyroid glands in uremic patients with secondary
      hyperparathyroidism and is more sensitive than US.

PMID- 9580139
TI  - "Blowout" as a sign of invasion of the laryngeal cartilage by cancer.

PMID- 9580140
TI  - Sonography as the primary screening technique for blunt abdominal trauma:
      experience with 899 patients.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy of sonography
      when used routinely as the primary screening technique for blunt abdominal
      trauma. SUBJECTS AND METHODS: From December 1994 through December 1995, we used
      sonography as the primary screening technique for the initial assessment of blunt
      abdominal trauma. Sonography was performed by dedicated technologists and
      overseen and interpreted by radiology residents or attending physicians. A
      positive study was defined as evidence of free fluid or parenchymal injury.
      Sonographic findings were correlated with CT, surgery, or clinical follow-up.
      RESULTS: Of the 899 sonograms obtained for blunt abdominal trauma, the findings
      of 783 were negative, 101 were positive, and 15 were indeterminate. Of the 783
      sonograms with negative findings, 768 (98%) were confirmed by CT, surgery, or
      clinical follow-up. Similarly, of the 101 sonograms with positive findings, 95
      (94%) were confirmed. Interpretations resulted in 15 false-negative and five
      false-positive examinations. For all sonograms, we calculated a sensitivity of
      86%, a specificity of 99%, and an accuracy of 98%. CONCLUSION: Sonography can be
      used effectively as the primary screening technique for blunt abdominal trauma.

PMID- 9580141
TI  - Gluten sensitivity in patients with primary biliary cirrhosis.
AB  - OBJECTIVE: Whereas celiac disease and primary biliary cirrhosis have been
      reported to coexist in the same patient, the frequency of this relationship has
      not been clarified. Nowadays, the concept of celiac disease has been extended
      from that of a severe enteropathy to a broader concept of gluten-driven
      intestinal immunological response. In this study we assessed features of gluten
      sensitivity in a cohort of patients with primary biliary cirrhosis. METHODS: Ten
      patients with primary biliary cirrhosis were evaluated a mean of 2 yr after
      diagnosis. The following features of gluten sensitivity were assessed: serum
      antigliadin and endomysial antibodies, small bowel histology (degree of atrophy
      and quantitative histological parameters), the presence of the typical celiac HLA
      genotype (DQ2), and intraepithelial lymphocyte response in the rectal mucosa
      after local gluten instillation (rectal gluten challenge). RESULTS: Overall,
      three patients presented evidence of gluten sensitivity. All three had abnormal
      titers of antigliadin antibody type IgA and one was positive for endomysial
      antibody. Two patients had partial villous atrophy. The rectal gluten challenge
      showed a celiac-like response, evidenced by an increase in intraepithelial
      lymphocyte infiltration after gluten exposure, in the three patients. The
      characteristic celiac HLA genotypes (DQA1 0501 and DQB1 0201) were identified in
      three patients. One of them also exhibited other features of gluten sensitivity.
      However, despite evidence of gluten intolerance, patients had minimal or no
      symptoms characteristic of celiac disease. CONCLUSION: We detected features of
      gluten sensitivity in a high proportion of patients with primary biliary
      cirrhosis. Further studies should be performed to elucidate the clinical
      significance of this association.

PMID- 9580142
TI  - Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1
      receptor antagonist in celiac disease. Are they related to the associated
      osteopenia?
AB  - OBJECTIVE: Decreased bone mineral density is a common finding in untreated celiac
      disease patients. However, the precise pathophysiology of osteopenia remains
      incompletely understood. Pathological features of gluten sensitivity are
      associated with local release of proinflammatory and antiinflammatory cytokines.
      We investigated the serum levels of IL-1beta, IL-6, and IL-1 receptor antagonist
      in celiac patients and correlated them with bone density measurements. METHODS:
      We assessed serum samples of 16 female patients at the time of diagnosis (on an
      unrestricted diet) and after a mean time of 37 months on a gluten-free diet. At
      the same time, bone mineral density in the lumbar spine and total skeleton was
      determined by DEXA. RESULTS: Untreated patients had high serum levels of IL-1beta
      and IL-6 and normal IL-1-RA. Treatment produced a decrease in median IL-1beta
      levels (p = NS) and a significant diminution of IL-6 (p < 0.05). On the contrary,
      IL-1-RA increased significantly after treatment (p < 0.05). Baseline lumbar spine
      Z-score and IL-6 levels exhibited a significant inverse correlation (r = -0.61; p
      < 0.01). Patients with more severe baseline osteopenia (< -2 Z-scores) had a
      significantly lower IL-1-RA than those with less bone compromise (> -2 Z-scores).
      CONCLUSIONS: Our data demonstrate that the inflammatory process observed in
      active celiac disease is associated with high serum levels of IL-1beta and IL-6
      and normal levels of IL-1-RA. Treatment significantly reduces both
      proinflammatory cytokines and significantly increases the antiinflammatory one.
      We also suggest that these cytokines might have a role in the osteopenia
      associated with celiac disease.

PMID- 9580143
TI  - Laryngeal tuberculosis in renal allograft patients.
AB  - Laryngeal tuberculosis, although the most common granulomatous disease of the
      larynx, is a rare form of extrapulmonary tuberculosis, never reported in
      immunosuppressed allograft recipients. We present two cases of laryngeal
      tuberculosis in renal transplant patients and a review of the literature. Two
      women, a 29-year-old and a 60-year-old, each more than 9 years after their
      cadaveric renal allograft, presented with a 2-week febrile illness with
      hoarseness and dysphagia, and both were found to have laryngeal tuberculosis by
      direct laryngoscopy. Although both radiographs were unremarkable, both patients
      had sputum positive for acid-fast bacilli that subsequently grew Mycobacterium
      tuberculosis. Clinical response promptly followed institution of isoniazid,
      rifampicin, and pyrazinamide in each case, although both required threefold
      increases in daily cyclosporin A dosage to maintain therapeutic levels.

PMID- 9580144
TI  - B2 kinin receptor upregulation by cAMP is associated with BK-induced PGE2
      production in rat mesangial cells.
AB  - In the rat mesangial cell (MC), activation of the bradykinin B2 receptor (B2R) by
      bradykinin (BK) is associated with both phospholipase C (PLC) and A2 (PLA2)
      activities and with inhibition of adenosine 3',5'-cyclic monophosphate (cAMP)
      formation leading to cell contraction. Because cAMP plays an important role in
      the regulation of gene expression in general, we investigated the effect of
      increasing the intracellular cAMP concentration ([cAMP]i) in mesangial cells on
      the B2 mRNA expression, on the density of B2 receptor binding sites, on the BK
      induced increase in both the free cytosolic Ca2+ concentration ([Ca2+]i), and in
      the prostaglandin E2 (PGE2) production. Forskolin, PGE2, and cAMP analog, 8
      bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), were used to increase
      [cAMP]i. Twenty-four-hour treatment with forskolin, PGE2, and 8-BrcAMP resulted
      in significant increases in B2 receptor binding sites, which were inhibited by
      cycloheximide. The maximum B2 receptor mRNA expression (160% above control) was
      observed in cells treated during 24 h with forskolin and was prevented by
      actinomycin D. In contrast, the D-myo-inositol 1,4,5-trisphosphate (IP3)
      formation and the BK-induced increase in [Ca2+]i, reflecting activation of PLC,
      were not affected by increased levels of [cAMP]i. However the BK-induced PGE2
      release, reflecting PLA2 activity, was significantly enhanced. These data bring
      new information regarding the dual signaling pathways of B2 receptors that can be
      differentially regulated by cAMP.

PMID- 9580145
TI  - Role of AT1 receptors in the renal papillary effects of acute and chronic nitric
      oxide inhibition.
AB  - Nitric oxide (NO) is a vasodilator substance controlling renal papillary blood
      flow (PBF) in the rat. In this study we have evaluated the role of AT1
      angiotensin II receptors as modulators of the whole kidney and papillary
      vasoconstrictor effects induced by the acute or chronic inhibition of NO
      synthesis. Experiments have been performed in anesthetized, euvolemic Munich
      Wistar rats prepared for the study of renal blood flow (RBF) and PBF. In normal
      rats, acute administration of the NO synthesis inhibitor N omega-nitro-L-arginine
      methyl ester (L-NAME) increased mean arterial pressure (MAP) and decreased RBF
      and PBF. Either acute or chronic treatment with the AT1 receptor blocker losartan
      did not modify the decreases in RBF or PBF secondary to L-NAME. In animals made
      hypertensive by chronic inhibition of NO, basal MAP was higher, whereas RBF and
      PBF were lower than in the controls. In these animals, acute or chronic
      administration of losartan decreased MAP and increased both RBF and PBF
      significantly. These results indicate that, under normal conditions, the
      decreases in RBF or PBF induced by the acute inhibition of NO synthesis are not
      modulated by AT1-receptor stimulation. However, the arterial hypertension, renal
      vasoconstriction, and reduced PBF present in chronic NO-deficient hypertensive
      rats is partially due to the effects of angiotensin II, via stimulation of AT1
      receptors.

PMID- 9580146
TI  - Lack of response of thrombocytopenia associated with human immunodeficiency virus
      to triple antiretroviral therapy.

PMID- 9580147
TI  - Effect of alendronate on cultured normal human osteoblasts.
AB  - Alendronate is an aminobisphosphonate with a potent anti-reabsorptive action that
      does not appear to interfere with bone mineralization, and is even able to
      increase bone mineral density in osteoporotic postmenopausal women through a
      still not fully understood mechanism. This study was conducted to assess the
      direct effect of alendronate on diverse aspects of normal human osteoblast
      physiology. For that purpose, the in vitro effect of a wide range of
      concentrations [from 10(-1) to 10(-12) mol/L] of alendronate on cell viability,
      proliferation, collagen synthesis, and the mineral-depositing capacity of normal
      human osteoblasts was tested. Alendronate effects were examined at 48 and 96 h of
      culture in the presence or absence of fetal calf serum. In vitro alendronate
      affected osteoblast viability at concentrations equal to or higher than 10(-4)
      mol/L. At concentrations equal to or higher than 10(-3) mol/L, no viable cells
      were observed in cultures. In vitro alendronate at concentrations between 10(-5)
      and 10(-12) mol/L did not have any effect on the proliferative capacity of normal
      human osteoblasts determined by two different techniques: (1) tritiated thymidine
      incorporation to DNA and (2) cell counting. Collagen synthesis by normal human
      osteoblasts showed a tendency to decrease following incubation with alendronate
      supplemented with fetal calf serum. This decrease was only statistically
      significant after 96 h of culture; however, a dose-response effect could not be
      documented. Finally, no effect of alendronate was observed on calcium deposition
      in vitro by normal human osteoblasts at concentrations equal to or lower than 10(
      5) mol/L. In conclusion, the present study shows that alendronate in vitro does
      not affect viability, proliferation, and mineral deposit capacity of normal human
      osteoblasts at the concentration at which it inhibits by 50% the resorptive
      capacity of osteoclasts that for this drug has been reported as 2 x 10(-9) mol/L.

PMID- 9580148
TI  - Systemic xanthohistiocytoma: a variant of xanthoma disseminatum?
AB  - We present a 66-year-old man who had maculopapular pigmented lesions on the skin
      of the head, neck and trunk suggesting generalized eruptive histiocytoma (GEH).
      These lesions had a yellowish centre in a target-like pattern that has not been
      previously described. The patient suffered from diplopia and had a severe
      sensorimotor polyneuropathy causing progressive paresis of the limbs. The
      explorations performed disclosed the presence of specific xanthomatous
      infiltrates in the skin, lungs, respiratory tract, peripheral nerves and
      meninges, suggesting xanthoma disseminatum (XD) or juvenile xanthogranuloma.
      Multiple osteolytic lesions of large bones were also found. The infiltrate was
      CD68, MAC 387 and factor XIIIa positive and S-100 and CD1 negative. Some cells
      contained worm-like bodies visible by electron microscopy. Our patient presented
      clinical and immunohistochemical findings suggestive of GEH, juvenile
      xanthogranuloma or XD, supporting the idea of a wide spectrum of non-Langerhans
      cell histiocytosis. These specific target-like xanthomatous lesions seem to be
      unique for this new variant of XD.

PMID- 9580149
TI  - The origin of Rhodnius prolixus in Central America.

PMID- 9580150
TI  - [Evaluation of body fluid compartments and their relationship with water
      electrolyte changes in obstructive jaundice].
AB  - BACKGROUND: The alteration of the mechanisms of water and sodium preservation may
      be an important factor in the development of acute postoperative renal failure in
      obstructive jaundice (OJ). Experimental OJ has been associated with a depletion
      of the extracellular volume and alteration of the mechanisms of regulation of
      hydrosaline metabolism. The aim of this study was to evaluate the distribution of
      the body volumes and the regulating hormones of hydrosaline metabolism in human
      OJ. PATIENTS AND METHOD: A prospective, clinical study evaluating 18 patients
      with OJ (9 females and 9 males) with a mean age of 69 +/- 8.9 years was
      performed. The plasma levels of antinatriuretic peptide (ANP), aldosterone and
      renin were determined. The body volumes were evaluated by tetrapolar
      bioimpedanciometry. The results of the patients with OJ were compared with a
      control group (CG) of 12 healthy subjects, matched for age and sex (6 females and
      6 males with a mean age of 64.5 +/- 14 years). RESULTS: High ANP values were
      observed in 87.5% of the patients. The results of the hormonal studies compared
      with the CG were: ANP (117.33 +/- 37.7 vs 41.31 +/- 16.8 pg/ml; p < 0.001),
      aldosterone (185.68 +/- 82.1 vs 44.3 +/- 21.6 pg/ml; p < 0.001) and renine (57.18
      +/- 69.9 vs 16.08 +/- 9.7 microU/ml; p < 0.05). Depletion of extracellular volume
      was found in 75% of the patients. CONCLUSIONS: Human obstructive jaundice is
      associated with an important alteration in the hormonal mechanisms of water and
      sodium regulation. This alteration is accompanied by a marked depletion of
      extracellular volume.

PMID- 9580151
TI  - [Intestinal obstruction and necrotizing thyroiditis secondary to Pneumocystis
      carinii infection in a seropositive hemophiliac patient seropositive for human
      immunodeficiency virus].
AB  - We report a case of bowel infection by Pneumocystis carinii (PC) that presented
      as an acute obstruction accompanied by intestinal hemorrhage (melena) in a HIV
      seropositive hemophilic patient. Laparotomy followed by resection of two plaque
      like jejunal tumors was performed, and intravenous therapy with pentamidine was
      initiated. No other organ was found to be affected by PC (not even the lung),
      with the exception of the thyroid gland. To our knowledge, this is the first
      reported case in which acute intestinal obstruction was the presenting symptom of
      extrapulmonary pneumocystosis.

PMID- 9580152
TI  - Effect of desialylated human chorionic gonadotropin (hCG) on the bioactivity of
      rat Leydig cells.
AB  - Human chorionic gonadotropin is a glycoprotein hormone that, like LH, stimulates
      steroidogenesis in gonadal cells. Using a desialylation process. 95 per cent of
      the sialic acid residues from an intact standard hCG molecule were eliminated and
      then the electrophoretic properties and the bioactivity of the desialylated hCG
      were determined. Using rat Leydig cells as a biological model, the binding
      affinity to LH receptors of Leydig cell membranes, steroidogenic activity and
      second messenger production were studied. The results indicate that the loss of
      sialic acid from the hCG molecule slightly increases the binding activity to LH
      receptors and results in steroidogenic activity with an increased ED50. Cyclic
      AMP production was significantly reduced however and arachidonic acid release was
      not observed. Several possible mechanisms that could explain these results are
      discussed.

PMID- 9580153
TI  - Inositolphosphoglycans possibly mediate the effects of glucagon-like peptide-1(7
      36)amide on rat liver and adipose tissue.
AB  - Insulin-like effects of glucagon-like peptide-1(7-36)amide (GLP-1) in rat liver,
      skeletal muscle and fat, and also the presence of GLP-1 receptors in these
      extrapancreatic tissues, have been documented. In skeletal muscle and liver, the
      action of GLP-1 is not associated with an activation of adenylate cyclase, and in
      cultured murine myocytes and hepatoma cell lines, it was found that GLP-1
      provokes the generation of inositolphosphoglycan molecules (IPGs), which are
      considered second messengers of insulin action. In the present work, we document
      in isolated normal rat adipocytes and hepatocytes that GLP-1 exerts a rapid
      decrease of the radiolabelled glycosylphosphatidylinositols (GPIs)--precursors of
      IPGs--in the same manner as insulin, indicating their hydrolysis and the
      immediate short-lived generation of IPGs. Thus, IPGs could be mediators in the
      GLP-1 actions in adipose tissue and liver, as well as in skeletal muscle, through
      GLP-1 receptors which are, at least functionally, different from that of the
      pancreatic B-cell.

PMID- 9580154
TI  - Age-related changes of lymphocyte subsets in normal bone marrow biopsies.
AB  - There is a paucity of information in the literature concerning the age-related
      changes of the lymphocyte subsets in bone marrow (BM), and the available reports
      disagree about the characteristics of the population studied and the methods for
      obtaining, handling, and analyzing the samples. The purpose of the present study
      was to determine the distribution of lymphoid subsets in the BM from infants,
      children, and adults by analyzing fragments of sternum obtained during
      cardiovascular surgery. The samples were studied by flow cytometry employing the
      whole blood lysis method and excluding from the analysis the contamination of the
      lymphoid window by erythroid precursors. We observed that in the first 4 years of
      life the B subset represented more than 65% of all cells in the lymphoid window,
      most of them (80%) exhibiting the immature phenotype CD19+CD100+. Conversely, the
      T subset was composed of mature CD4+ or CD8+ cells, with the CD4/CD8 ratio being
      less than 1 in all age groups. With age there was a progressive decrease in the
      percentage of B cells and an increase of T cells, reaching similar proportions in
      the BM from adults (33.6% and 34.8%, respectively). Furthermore, the percentage
      of CD10+ cells in the B subset decreased independently, whereas the CD20
      expression increased. The percentage of NK cells did not change with age.

PMID- 9580155
TI  - Mechanism of the leakage induced on lipid model membranes by the hemolytic
      protein sticholysin II from the sea anemone Stichodactyla helianthus.
AB  - A potent hemolytic polypeptide, sticholysin II, has been purified to homogeneity
      from the sea anemone Stichodactyla helianthus. The protein produces leakage of
      aqueous contents of model lipid vesicles composed of either phosphatidylcholine
      or sphingomyelin if cholesterol is present in these membranes. The leakage has
      been analyzed by measuring the dequenching of the fluorescent dye 8
      aminonaphthalene-1,3,6-trisulfonic acid, coencapsulated with its quencher N,N'-p
      xylenebispyridinium bromide, upon dilution of the vesicle contents into the
      external medium. The protein displays a maximum effect on vesicles containing 20
      25% cholesterol. Leakage is also produced in vesicles composed of mixtures of
      phosphatidylcholine and sphingomyelin, the maximum effect being observed for 20
      30% sphingomyelin molar content. The extent of the leakage is dependent on the
      molecular mass of the vesicle entrapped solutes in the range 445-960 Da. This
      suggests the involvement of a pore of about 1 nm in diameter based on the
      limiting size observed for the leakage of the different solutes. Oligomerization
      of the protein is apparently involved in the membrane permeabilization, based on
      the kinetic analysis of the leakage process which is shown to proceed through an
      all-or-none mechanism.

PMID- 9580156
TI  - The cytotoxin alpha-sarcin behaves as a cyclizing ribonuclease.
AB  - The hydrolysis of adenylyl(3'-->5')adenosine (ApA) and guanylyl(3'-->
      5')adenosine (GpA) dinucleotides by the cytotoxic protein alpha-sarcin has been
      studied. Quantitative analysis of the reaction has been performed through reverse
      phase chromatographic (HPLC) separation of the resulting products. The hydrolysis
      of the 3'-5' phosphodiester bond of these substrates yields the 2'-3' cyclic
      mononucleotide; this intermediate is converted into the corresponding 3'
      monophosphate derivative as the final product of the reaction. The values of the
      apparent Michaelis constant (KM), kcat and kcat/KM have also been calculated. The
      obtained results fit into a two-step mechanism for the enzymatic activity of
      alpha-sarcin and allow to consider this protein as a cyclizing RNase.

PMID- 9580158
TI  - Chronic exposure to aluminum impairs neuronal glutamate-nitric oxide-cyclic GMP
      pathway.
AB  - Humans are exposed to aluminum from environmental sources and therapeutic
      treatments. However, aluminum is neurotoxic and is considered a possible
      etiologic factor in Alzheimer's disease and other neurological disorders. The
      molecular mechanism of aluminum neurotoxicity is not understood. We tested the
      effects of aluminum on the glutamate-nitric oxide-cyclic GMP pathway in cultured
      neurons. Neurons were exposed to 50 microM aluminum in culture medium for short
      term (4 h) or long-term (8-14 days) periods, or rats were prenatally exposed,
      i.e., 3.7% aluminum sulfate in the drinking water, during gestation. Chronic (but
      not short-term) exposure of neurons to aluminum decreased glutamate-induced
      activation of nitric oxide synthase by 38% and the formation of cyclic GMP by
      77%. The formation of cyclic GMP induced by the nitric oxide-generating agent S
      nitroso-N-acetylpenicillamine was reduced by 33%. In neurons from rats prenatally
      exposed to aluminum but not exposed to it during culture, glutamate-induced
      formation of cyclic GMP was inhibited by 81%, and activation of nitric oxide
      synthase was decreased by 85%. The formation of cyclic GMP induced by S-nitroso-N
      acetylpenicillamine was not affected. These results indicate that chronic
      exposure to aluminum impairs glutamate-induced activation of nitric oxide
      synthase and nitric oxide-induced activation of guanylate cyclase. Impairment of
      the glutamate-nitric oxide-cyclic GMP pathway in neurons may contribute to
      aluminum neurotoxicity.

PMID- 9580157
TI  - Lipopolysaccharide intranigral injection induces inflammatory reaction and damage
      in nigrostriatal dopaminergic system.
AB  - The pathogenesis of Parkinson's disease is still poorly understood. To address
      the hypothesis that immune-mediated events, such as microglial activation, may be
      involved in the dopaminergic neurodegeneration, we have studied the effect that
      intranigral injection of the immunostimulant lipopolysaccharide has on
      monoaminergic neurotransmitters in rats. Activation of microglial cells,
      visualized by immunohistochemistry with a specific monoclonal antibody, was
      already obvious 2 days after injection. In relation to the biochemical parameters
      studied, we found a significant decrease of dopamine levels in both the
      substantia nigra and striatum up to at least 21 days after intranigral injection
      of lipopolysaccharide. This result was supported by the decrease in tyrosine
      hydroxylase activity and the loss of tyrosine hydroxylase-positive neuronal
      bodies, shown by immunohistochemistry. These alterations of the dopaminergic
      system did not reverse during the interval studied (21 days); conversely, the
      serotoninergic system suffered only transient damage. In addition, we found that
      the neurotoxic effect of lipopolysaccharide was not mediated by nitric oxide.
      Based on our results we suggest that the nigrostriatal dopaminergic system is
      susceptible to damage by inflammatory events and that these may be implicated in
      neurodegeneration processes such as Parkinson's disease.

PMID- 9580159
TI  - The mechanisms involved in formation of deletions and duplications of 15q11-q13.
AB  - Haplotype analysis was undertaken in 20 cases of 15q11-q13 deletion associated
      with Prader-Willi syndrome (PWS) or Angelman syndrome (AS) to determine if these
      deletions arose through unequal meiotic crossing over between homologous
      chromosomes. Of these, six cases of PWS and three of AS were informative for
      markers on both sides of the deletion. For four of six cases of paternal 15q11
      q13 deletion (PWS), markers on both sides of the deletion breakpoints were
      inferred to be of the same grandparental origin, implying an intrachromosomal
      origin of the deletion. Although the remaining two PWS cases showed evidence of
      crossing over between markers flanking the deletion, this was not more frequent
      than expected by chance given the genetic distance between proximal and distal
      markers. It is therefore possible that all PWS deletions were intrachromosomal in
      origin with the deletion event occurring after normal meiosis I recombination.
      Alternatively, both sister chromatid and homologous chromosome unequal exchange
      during meiosis may contribute to these deletions. In contrast, all three cases of
      maternal 15q11-q13 deletion (AS) were associated with crossing over between
      flanking markers, which suggests significantly more recombination than expected
      by chance (p = 0.002). Therefore, there appears to be more than one mechanism
      which may lead to PWS/AS deletions or the resolution of recombination
      intermediates may differ depending on the parental origin of the deletion.
      Furthermore, 13 of 15 cases of 15q11-q13 duplication, triplication, or inversion
      duplication had a distal duplication breakpoint which differed from the common
      distal deletion breakpoint. The presence of at least four distal breakpoint sites
      in duplications indicates that the mechanisms of rearrangement may be complex and
      multiple repeat sequences may be involved.

PMID- 9580160
TI  - Inducible gene expression from African swine fever virus recombinants: analysis
      of the major capsid protein p72.
AB  - A method to study the function of individual African swine fever virus (ASFV)
      gene products utilizing the Escherichia coli lac repressor-operator system has
      been developed. Recombinant viruses containing both the lacI gene encoding the
      lac repressor and a strong virus late promoter modified by the insertion of one
      or two copies of the lac operator sequence at various positions were constructed.
      The ability of each modified promoter to regulate expression of the firefly
      luciferase gene was assayed in the presence and in the absence of the inducer
      isopropyl beta-D-thiogalactoside (IPTG). Induction and repression of gene
      activity were dependent on the position(s) of the operator(s) with respect to the
      promoter and on the number of operators inserted. The ability of this system to
      regulate the expression of ASFV genes was analyzed by constructing a recombinant
      virus inducibly expressing the major capsid protein p72. Electron microscopy
      analysis revealed that under nonpermissive conditions, electron-dense membrane
      like structures accumulated in the viral factories and capsid formation was
      inhibited. Induction of p72 expression allowed the progressive building of the
      capsid on these structures, leading to assembly of ASFV particles. The results of
      this report demonstrate that the transferred inducible expression system is a
      powerful tool for analyzing the function of ASFV genes.

PMID- 9580162
TI  - [Incidence and current clinical spectrum of tuberculosis in a metropolitan area
      in the south of Spain].
AB  - BACKGROUND: To study the incidence and clinical spectrum of tuberculosis in the
      metropolitan area of Malaga (Spain). METHODS: Prospective study which includes
      all patients who had a diagnosis of tuberculosis within the referral area of
      "Carlos Haya" Malaga Regional Hospital from March 1, 1993 to February 28, 1994.
      RESULTS: During the study period, there were 138 cases of tuberculosis, with an
      incidence of 43.7 cases/10(5) inhabitants. Ninety one cases (66%) were male, and
      the mean age (SD) was 33.2 (18.3), with 88% being less than 55 years old. Thirty
      six patients (26.1%) were HIV-infected. Extrapulmonary tuberculosis made up 27.5%
      of the cases, and was more frequent in HIV-infected patients (p < 0.01; odds
      ratio: 2.9; 95% CI: 1.2-7.1). The mean (SD) time to diagnosis was 54.3 (76) days.
      The diagnosis was microbiologically confirmed in 106 cases (76.8%),
      histologically in 14 cases (10.1%), and the remaining 18 cases (13.1%) were
      clinically diagnosed. The global rate of resistance was 10.8%. The rate of
      primary resistance was 4.6%, and the rate of multidrug-resistant tuberculosis was
      3.1%. Eighty nine patients (77.4%) were cured, six patients (5.2%) stopped the
      treatment, 3 (2.6%) had relapses and 1 (0.9%) was considered a therapeutic
      failure; 16.7% of patients were lost for follow-up. Sixteen patients died and in
      nine of them (6.5%) the death was attributed to tuberculosis. CONCLUSIONS: The
      incidence of tuberculosis in Malaga urban area is high. It mainly affects young
      males of unfavored socio-economic classes. HIV-infected patients account for a
      high percentage of the cases. The high number of productive cases and the long
      time to diagnosis evidence the shortcomings of our sanitary system. These facts,
      together with the high rate of non-compliance, of treatment may explain the
      seriousness of the current situation in our country.

PMID- 9580161
TI  - [Primary gastrointestinal lymphomas: response to eradicative therapy and
      prognostic factors in 52 patients].
AB  - BACKGROUND: To analyze the response to eradicative therapy and prognostic factors
      in 52 patients with primary gastrointestinal lymphoma (PGIL) diagnosed at a
      single institution in a 13 year period. PATIENTS AND METHODS: The main clinical,
      biological and evolutive data were recorded. Pathologic diagnosis of PGIL was
      made according to the Working Formulation. Clinical stage was determined by the
      Ann Arbor system modified by Mushoff. The results of therapy as well as the
      influence of such characteristics on complete remission (CR), disease-free
      survival (DFS) and overall survival (OS) were studied. RESULTS: Mean age of the
      series was 53 years (SD 15). Thirty patients were males. HIV infection preceded
      PGIL diagnosis in 10 cases. Seventeen had bad performance status (ECOG 2-4) and
      30 B symptoms. The PGIL localization was gastric in 31 cases and 29 had a low
      grade malignant lymphoma. B phenotype was demonstrated in 98% and 22 patients
      presented advanced stages (IIE2-IV). Treatment was radical surgery followed by
      intensive chemotherapy in 32 cases, intensive chemotherapy alone in 17, and
      surgical resection in 3. CR was obtained in 34 patients and 6 of them relapsed.
      The projected DFS from CR at 9 years was 72% and OS was 26%. CR and survival were
      not influenced by PGIL localization and treatment type. The main unfavourable
      prognostic factors were advanced stage (CR and OS), B symptoms (DFS and OS) and
      advanced ECOG score (CR, DFS and OS). Previous HIV infection had an independent
      prognostic influence on both CR and OS. CONCLUSIONS: In patients with PGIL, the
      achievement of CR, DFS and survival have been independent of the type of
      eradicative treatment used. Performance status, B symptoms and clinical stage
      have been the main prognostic factors. HIV infection carried an independent
      prognostic significance.

PMID- 9580163
TI  - [Plasma cell tumors associated with HIV infection].

PMID- 9580164
TI  - Preliminary study of the potential vasodilator effects on rat aorta of centaurein
      and centaureidin, two flavonoids from Centaurea corcubionensis.
AB  - In this work, the potential vasorelaxant activity of centaurein and centaureidin,
      two flavonoids from Centaurea corcubionensis, were studied for the first time in
      rat aorta. Centaureidin (10 microM-0.1 mM) totally relaxed, in a concentration
      dependent manner and with almost equal effectiveness, the contractions induced by
      NA (IC50 = 16.7 +/- 1.9 microM) or by a high K+ concentration (IC50 = 16.1 +/-
      3.1 microM) in intact rat aortic rings. Mechanical removal of endothelium did not
      significantly modify the vasoralexant effects of this flavone (IC50 = 20.8 +/-
      2.4 microM for NA; IC50 = 21 +/- 2.9 microM for K+). On the other hand,
      centaurein (1 microM-0.1 mM) had no effect on NA- and high K(+)-induced
      contractions in rubbed and intact rat aortic rings. These results indicate that
      substitution by glucose in the chemical structure of centaureidin leads to the
      loss of its vasodilator activity.

PMID- 9580165
TI  - [Prognostic evaluation of post-infarction patients using two-dimensional
      echocardiography, late ventricular potentials and baroreflex sensitivity].
AB  - BACKGROUND: Although many variables are useful predictors of post-infarction
      mortality, their predictive positive values are weak when applied individually.
      The aim of this study was to determine the prognostic value of the combination of
      left ventricular ejection fraction, ventricular late potentials and baroreflex
      sensitivity. PATIENTS AND METHODS: We studied 69 consecutive post-infarction
      patients. On the day of their discharge from the coronary unit, all patients
      underwent a two-dimensional echocardiography, to determine the ejection fraction
      as well as a high resolution electrocardiogram to detect late potentials. To a
      subset of 49 patients was carried out to learn their baroreflex sensitivity. The
      patients were followed for 14 +/- 7 months and the following cardiac end points
      were considered: sudden cardiac death, non sudden cardiac death and non-fatal
      episodes of sustained ventricular tachycardia or ventricular fibrillation.
      RESULTS: There were 8 end points: 3 sudden cardiac deaths, 3 non sudden cardiac
      deaths and 2 successfully resuscitated sustained ventricular tachycardia
      episodes. The rate of fibrinolysis was 55%. An ejection fraction < 45%, the
      presence of late potentials and a baroreflex sensitivity < 3.0 msec/mmHg were
      univariate predictors with predictive positive values of 33%, 24% and 16%,
      respectively. When ejection fraction < 45%, late potentials and baroreflex
      sensitivity < 3.0 were combined, we found a significant increase in the positive
      predictive value (50%). CONCLUSION: The combined determination of ejection
      fraction, ventricular late potentials and baroreflex sensitivity allows us to
      identify subset postinfarction patients with a high rate of cardiac
      complications.

PMID- 9580166
TI  - [Elective noninvasive test in the diagnosis of coronary disease in the aged].
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the best
      noninvasive test to diagnose coronary artery disease in the elderly. PATTERNS AND
      METHODS: We conducted a study on 56 elderly patients (> 65 years) with chest pain
      and no previous history of coronary artery disease. They underwent exercise
      stress test, dipyridamole echocardiography (0.84 mg/kg), dobutamine
      echocardiography (up to a total dose of 40 microgram/kg/min and atropine when it
      was necessary), dobutamine MIBI-SPECT and coronary angiography. RESULTS:
      Angiography detected significant coronary artery disease in 41 patients. All
      tests used in this study had a similar sensitivity (conclusive exercise stress
      test 87%, dipyridamole echocardiography 83%, dobutamine echocardiography 80% and
      MIBI-SPECT 87%; p = NS). Coronary angiography did not identify significant
      lesions in 15 patients. Specificity of conclusive exercise stress test,
      dipyridamole and dobutamine echocardiography was similar (75%, 100% and 93%
      respectively; p = NS). However, the specificity of stress echocardiography was
      higher than that of scintigraphy (100% vs 66%; p = 0.02 for dipyridamole
      echocardiography and 93% vs 66%; p = 0.07 for dobutamine echocardiography).
      Diagnostic accuracy of each test was similar. CONCLUSIONS: Exercise stress test
      remains the non invasive diagnostic test of choice to detect coronary disease in
      the elderly. If this test is inconclusive, both stress echocardiography and
      isotopic studies are useful, although the specificity of stress echocardiography
      is higher than that of scintigraphy.

PMID- 9580168
TI  - [Dual-chamber pacemakers in obstructive hypertrophic cardiomyopathy: gradient
      variation with stress echocardiography].
AB  - INTRODUCTION: Permanent cardiac pacing with a dual chamber pacemaker has become a
      valid alternative in treatment of patients with obstructive hypertrophic
      cardiomyopathy and refractory symptoms to pharmacological treatment, with a
      significant decrease of left ventricular outflow tract gradient. AIM: To assess
      any modification of the gradient with dobutamine stress echocardiography.
      PATIENTS AND METHODS: We study 10 patients with obstructive hypertrophic
      cardiomyopathy and angina and/or dyspnea refractory to customary pharmacological
      treatment. A dual chamber pacemaker had been implanted 3-6 months previously. A
      dobutamine stress echocardiography was performed, beginning with a 10
      microgram/kg/min infusion, with increases of 10 micrograms each 3 minutes until a
      maximum of 40. Modification of subaortic gradient, severity of systolic anterior
      motion of mitral valve (SAM, degree 0-3/3) and severity of mitral regurgitation
      (degree 0-4/4) were assessed. RESULTS: Subaortic gradient decreased in all
      patients after pacemaker implantation (90 +/- 15 vs 20 +/- 10 mmHg; p < 0.001).
      With stress echocardiography the gradient increased in all patients (20 +/- 10 to
      101 +/- 13 mmHg; p < 0.001). After implant there were only two patients with a +1
      SAM, while during stress echocardiography SAM developed in all patients in +2 or
      +3 degree. Three patients had +1 mitral regurgitation after pacemaker
      implantation but during stress echocardiography 2-4/4 mitral regurgitation
      developed in all patients. CONCLUSIONS: Permanent dual chamber pacing decreased
      left ventricular outflow tract gradient in patients with obstructive hypertrophic
      cardiomyopathy, but during dobutamine stress echocardiography obstruction
      echocardiographic signs appeared.

PMID- 9580167
TI  - [Anatomopathological bases of latent ventricular dysfunction in insulin-dependent
      diabetics].
AB  - INTRODUCTION AND OBJECTIVES: The natural history of diabetic cardiomyopathy
      remains unclear, mainly due to concurrent coronary disease or hypertension. Since
      the presence of confounding factors is less likely in youngsters, they constitute
      a suitable study model to analyze early stages of diabetic cardiomyopathy.
      PATIENTS AND METHODS: We screened 33 young normotensive asymptomatic patients
      with type I diabetes mellitus. Mean age was 28 +/- 8 y (range 18 to 46 y) and
      there were 14 men. RESULTS: 2-D Echo showed normal left ventricular size and wall
      motion in all patients but one. Radionuclide basal ejection fraction was 56.5 +/-
      6.6% and increased to 63 +/- 7.4% (p < 0.02) on exercise. According to Rozansky
      criteria, 16 patients had an abnormal response. Abnormal stress sestamibi was
      detected in 18 patients and only 3 had reversible defects. Coronary angiography
      was performed in 11 patients with at least one abnormal non-invasive study
      response. Coronary angiography revealed normal vessels in all patients and left
      anterior descending blood flow velocity (Doppler) increased 4 fold after
      papaverine infusion. Left ventricular biopsies showed hypertrophy (either nuclear
      or cellular) in 11, myocytolysis in 6, interstitial fibrosis in 9 and lipid
      deposits in 4. Morphometric analysis of cardiac samples comparing the diabetic
      group and a control group showed that the volume fraction of fibrosis (0.19 +/-
      0.06 vs 0.10 +/- 0.06; p < 0.01), fiber area -mu2- (1,062 +/- 547 vs 600 +/- 167;
      p < 0.02) and fiber diameter -mu- (24.2 +/- 3.3 vs 15.1 +/- 3.4; p < 0.001) were
      higher in the former; and volume fraction of the myocytes was higher in the
      latter (0.71 +/- 0.006 vs 0.89 +/- 0.07; p < 0.001). CONCLUSIONS: Left
      ventricular dysfunction, not related to coronary atherosclerosis or small vessel
      disease, is frequent in asymptomatic young diabetic patients. Abnormal pathologic
      findings are common in the type of cell hypertrophy, interstitial fibrosis,
      myocytolysis and lipid deposits.

PMID- 9580170
TI  - Experimental pancreas transplantation: the consequences of portocaval shunt on
      blood glucose, plasma insulin, and glucagon.

PMID- 9580171
TI  - Genetics of inflammatory bowel disease: implications for the future.
AB  - There is overwhelming evidence that genetic factors play a role in the
      predisposition to suffer the development of the chronic inflammatory bowel
      diseases. The genetic analysis of complex diseases, such as ulcerative colitis
      and Crohn's disease, is difficult. The presence of disease heterogeneity, the
      relative low frequency in the population, the degree to which first-degree
      relatives are affected (approximately 10%), the presence of genes with minor
      genetic effects, and ethnic differences are some of the difficulties encountered
      when identifying disease susceptibility loci. Two major approaches to identifying
      these genes are being followed at present. The first, family-based, consists of
      studying linkage analysis in sibling pairs and parental transmission in genome
      wide screening using microsatellite markers. These studies are appropriate and
      helpful for finding genes of major or moderate effects but may provide difficulty
      when identifying genes with minor effects. Risch and Merikangas have pointed to
      the power of association studies utilizing candidate genes in families. These
      studies should be considered in the future in genome-wide screens when
      technologic advances permit. The second approach is based on classic
      epidemiologic designs, population-based studies, using candidate genes in the
      framework of a biologic hypothesis. Recent data using both approaches in both
      Crohn's disease and ulcerative colitis are reviewed. The results of genome-wide
      linkage studies have not reached consensus but suggest that these diseases are
      different and polygenic in nature. We have started our studies with the
      hypothesis that an abnormal immune dysbalance contributes to the biologic basis
      of disease. We therefore study polymorphisms in genes encoding proinflammatory
      and regulatory cytokines. Preliminary data of these association studies suggest
      the importance of several genes with small effects in determining the severity
      and prognosis of these diseases.

PMID- 9580169
TI  - Cyclosporine increases renal parathyroid hormone-related protein expression in
      vivo in the rat.
AB  - BACKGROUND: Clinical use of cyclosporine (CsA) is limited by its known
      nephrotoxicity. Parathyroid hormone (PTH)-related protein (PTHrP) increases after
      acute renal ischemia and stimulates proliferation of renal cells in culture.
      Herein, we have examined whether the renal expression of PTHrP and its PTH/PTHrP
      receptor is affected by chronic CsA nephrotoxicity. METHODS: Rats were randomly
      assigned to receive daily intramuscular injections of either CsA (25 mg/kg) or
      the same volume of the vehicle olive oil (control) for 3 weeks. At this time
      interval, under ether anesthesia, rat blood and kidneys were obtained for
      analytical determinations, and total RNA isolation or immunohistochemistry,
      respectively. RESULTS: Serum urea was 11+/-2 and 6+/-1 mmol/L (P < 0.01) in CsA
      treated and control rats, respectively. We found that PTH/PTHrP receptor mRNA was
      unchanged, but PTHrP mRNA, and also transforming growth factor-beta1 mRNA
      expression as positive control, was about twofold increased in the kidney of CsA
      treated rats. This was accompanied by increased PTHrP immunostaining in renal
      cortical tubules, associated with tubule vacuolation. CONCLUSION: This study
      demonstrates an up-regulation of PTHrP, associated with chronic CsA-induced
      nephrotoxicity. Our findings support a role for PTHrP in the CsA-injured kidney.

PMID- 9580172
TI  - Administration of antibiotics to patients with rupture of membranes at term: a
      prospective, randomized, multicentric study. Collaborative Group on PROM.
AB  - OBJECTIVE: To assess whether antibiotic administration changes the rate of
      materno-fetal infectious morbidity in premature rupture of membranes occurring
      later than 35 weeks of gestation. METHODS: A prospective, randomized and
      multicentric study in the Perinatology Units of eleven hospitals in Spain. Women
      were randomized to either antibiotic administration or control group. All were
      induced, if labor had not started spontaneously after 12 hours of ruptured
      membranes. Main outcome measures were maternal infection (chorioamnionitis and
      endometritis) and neonatal infectious morbidity (neonatal sepsis, meningitis and
      bronchopneumonia). RESULTS: Seven hundred and thirty-three patients were enrolled
      in the study, 371 in the antibiotics group and 362 in the control group. The
      incidence of chorioamnionitis and puerperal endometritis were reduced but the
      differences are statistically nonsignificant. However, the incidence of neonatal
      sepsis was significantly lower in newborns to mothers who had received
      antibiotics, 1 vs. 7 cases (Fisher's exact test, p<0.007). CONCLUSION: The study
      strongly suggests that prophylactic use of antibiotics in premature rupture of
      membranes occurring at 36 or more weeks of gestation reduces the risk of neonatal
      sepsis and probably maternal endometritis.

PMID- 9580173
TI  - Variations in cotinine levels in smokers during and after pregnancy.
AB  - OBJECTIVE: To compare the antenatal and postnatal cotinine levels in smoking
      women after controlling for the differences in smoking practices. STUDY DESIGN: A
      paired comparison of two measurements of cotinine concentration was conducted in
      40 smoking women voluntarily recruited in a prenatal education program held in La
      Fe Hospital, Valencia, Spain, during 1990 and 1991. Cotinine concentration was
      assayed by gas chromatography in samples of saliva obtained during and after
      pregnancy. The Wilcoxon matched-pairs test and multiple linear regression
      analysis were used. RESULTS: The cotinine per cigarette ratio during pregnancy
      (median 3.53 ng/ml per cigarette) was significantly lower than the ratio in the
      postnatal testing (median 9.87 ng/ml per cigarette). This difference persisted
      after allowing for differences in reported cigarette consumption. CONCLUSION:
      These findings suggest that the available equivalencies between cotinine level
      and nicotine intake obtained from adult nonpregnant populations cannot be
      directly applied during pregnancy.

PMID- 9580175
TI  - The production of MLR-blocking factors after lymphocyte immunotherapy for RSA
      does not predict the outcome of pregnancy.
AB  - PROBLEM: The questions of whether production of mixed lymphocyte reaction
      blocking factors (MLR-BFs) after immunotherapy with lymphocytes for recurrent
      spontaneous abortion (RSA) has prognostic value and whether cytotoxic antibodies
      are also involved were tested. METHOD OF STUDY: A prospective study with 33
      patients who had a history of two or more abortions, lacking MLR-BFs, was carried
      out. The patients received immunizations with lymphocytes and 6 weeks or later
      were tested for seroconversion of MLR-BFs. Seventeen of these thirty-three
      patients were evaluated for antipaternal cytotoxic antibodies. The results were
      correlated with the outcome of the next pregnancy after treatment. RESULTS:
      Eighty percent of the 33 patients had a live child. Of those patients having
      success, only 50% produced MLR-BFs. Of those patients having a new loss, five did
      and two did not produce MLR-BF (P > 0.05). Regarding the 17 patients tested for
      cytotoxic antibodies, 4 of the 5 patients who tested positive had a new abortion,
      whereas only 1 of 12 whose tests remained negative did not have gestational
      success (P < 0.01). CONCLUSION: The presence of MLR-BFs is not a prognostic
      criterium for the outcome of pregnancy after alloimmunotherapy, and,
      consequently, it is not a good diagnostic tool for RSA of alloimmune cause.

PMID- 9580174
TI  - Olfactory neuroblastoma is not related to the Ewing family of tumors: absence of
      EWS/FLI1 gene fusion and MIC2 expression.
AB  - The relationship of olfactory neuroblastoma to the Ewing sarcoma family of tumors
      remains controversial due to its variable histopathology and to conflicting or
      inconsistent cytogenetic, immunophenotypic, and molecular data. To address this
      issue, we performed a morphologic, immunohistochemical, and molecular study of 20
      olfactory neuroblastomas. Morphologically, the tumors consisted of nests of
      primitive small, round, blue cells, usually set in a background of
      neurofibrillary stroma. Immunohistochemical stains revealed strong reactivity for
      neuroendocrine markers (synaptophysin, chromogranin, neuron-specific enolase) and
      only focal staining for cytokeratins in two cases. Immunostaining with antibody
      O13 to the Ewing sarcoma-associated MIC2 antigen was uniformly negative (0 of
      17). Amplifiable RNA was extracted from paraffin-embedded tissue blocks of 11
      cases, and no evidence of the chimeric EWS/FLI transcript, characteristic of
      Ewing sarcoma, was found in any case. The EWS gene was not rearranged using
      Southern blot analysis in one additional case in which high molecular weight DNA
      was available. These results disagree with the proposed classification of
      olfactory neuroblastoma in the Ewing sarcoma family of tumors and suggest that
      therapy developed for the latter tumor group may not be biologically rational for
      olfactory neuroblastoma.

PMID- 9580176
TI  - A modulatory role for substance P on the regulation of luteinizing hormone
      secretion by cultured porcine gonadotrophs.
AB  - Substance P (SP) has been suggested to regulate gonadotroph function both
      directly and indirectly in different species. In pigs, the possible role of
      hypothalamic and pituitary SP in the control of LH release has not been examined.
      Here, we investigated SP effects on basal and GnRH-stimulated LH secretion by
      porcine gonadotrophs in vitro, in both static and dynamic culture systems. SP
      concentrations of 100 nM or above stimulated LH release from monolayer cultures
      without affecting intracellular LH content. In the same cultures, SP potentiated
      GnRH (10 nM)-stimulated LH release and reversed the GnRH-induced decrease of
      gonadotroph LH stores. The GnRH, but not the SP, effect was completely blocked by
      the potent GnRH-receptor antagonist antide. In superfused pituitary fragments,
      three successive pulses of SP or GnRH also stimulated LH release, yet the
      combined administration of both factors did not result in a synergistic
      stimulation. These results demonstrate that SP acts directly on porcine
      gonadotrophs to stimulate LH release, and to maintain the levels of hormonal
      stores, through a GnRH receptor-independent mechanism. Furthermore, our findings
      suggest that continuous exposure of gonadotrophs to SP would potentiate GnRH
      stimulated LH secretion, thus supporting a possible role of SP as modulator of
      porcine gonadotroph function.

PMID- 9580177
TI  - [Primary polycythaemia vera in the elderly].
AB  - We present an 86-years-old woman's case with paralysis in her left hand of abrupt
      apparition, accompanied by arterial hypertension and dizziness. The investigation
      revealed erythrocytosis, leukocytosis, thrombocytosis, with normal arterial O2
      saturation (O2 SAT), increased of his red cell volume and blood viscosity. The
      polycythaemia vera (PV) was diagnose and the paralysis disappeared, when 24 hours
      before a phlebotomy was practiced, and the function was recovered by the hand. We
      analysed the presents diagnostics criteria of the disease defined by
      Polycythaemia Vera Study Group (PVSG). The different treatments for PV are
      discussed; in addition to venesection, conventional treatment include
      chemotherapy with hydroxyurea and pipobroman, as well as the erythropheresis, 
      interferon and aspirin. All of the treatments are associated with complications;
      thrombotic in the case of phlebotomy; malignancies and gastrointestinal bleeding
      in the case of myelosuppressive treatments and aspirin. We think the optimal
      treatment for PV is a judicious combination of the available alternatives,
      depending on the phase of the disease, and the age of the patient.

PMID- 9580178
TI  - [Multiple pulmonary nodules as a manifestation of varicella].
AB  - It is presented the case of pulmonary affectation by varicella in a woman with
      bronchial asthma. The hemoptysis and the multiple pulmonary nodules presence have
      been the principal manifestations of this entity. As evolution; to emphasize the
      of the hemoptysis and the radiological normality.

PMID- 9580179
TI  - [Whipple's disease: early diagnosis through articular disease and
      hyperpigmentation].
AB  - We present a new case of Whipple's disease. The patient have a clinical history
      of steatorrhea and diarrhea of various years of evolution with hyperpigmentation
      of skin and mucosae and migratory polyarthralgias with inflammatory sings. The
      biochemicals analysis for rheumatoid and endocrinological diseases were
      negatives. A endoscopically yeyunal biopsy was performed and the diagnosis of
      Whipple's disease was made. We comment this clinical presentation of Whipple's
      disease with a seronegative inflammatory rheumatological disease. The
      differential diagnosis with seronegative arthritis was emphasized.

PMID- 9580180
TI  - [A comparative study of western blot interpretation criteria for Lyme disease
      serological diagnosis in our environment].
AB  - We have studied the WB reliability for the Lyme disease (LD) serological
      diagnosis. Twenty five samples (20 sera and 5 CSF) from 5 patients with LD,
      according to CDC criteria were analyzed. The syphilis was excluded in every
      patient. Borrelia burgdorferi antibodies were assessed by an indirect ELISA (IgG
      + IgM, B31 strain). Intrathecal antibodies in CSF were studied in patients with
      neurological diseases. Positive samples by ELISA were reanalyzed by WB according
      to the manufacturer, Tilton and Dressler criteria and presence either 93, 39, 34
      or 23 kDa band for IgG. Four patients were controlled and one of them (25%)
      became negative the antibodies (serorreversion). Three of them, who had
      neurological symptoms, displayed intrathecal antibodies. WB sensibility for LD
      according to the manufacturer, Tilton, Dressler and any of the four IgG bands was
      26.31%, 42.1%, 21% and 84% for IgG and 52.6%, 47.3% and 42.1% for IgM
      respectively. Tilton and Dressler criteria may not be as sensible as 93, 39, 34
      or 23 kDa IgG bands for the diagnosis of LD in our environment.

PMID- 9580181
TI  - Solid-phase extraction and high-performance liquid chromatography procedures for
      the analysis of paralytic shellfish toxins.
AB  - Paralytic shellfish poisoning (PSP) toxins are produced by certain dinoflagellate
      species such as Gymnodinium catenatum and Alexandrium tamarensis, during certain
      periods of the year influenced by several environmental factors, affecting the
      aquaculture industry and mainly bivalve molluscs. HPLC with fluorescence
      detection is a powerful analytical technique for the analysis of such toxins;
      several HPLC alternatives have been developed in order to improve the liquid
      chromatographic analysis, but due to the complexity of the sample matrix,
      important work has been focused recently on the clean-up of samples prior to HPLC
      analysis. Solid-phase extraction procedures offer advantages for this clean-up.
      In this work we focus on the study of three different clean-up methods prior to
      HPLC with fluorescence detection analysis of PSP toxin present in contaminated
      mussel samples; by spiking uncontaminated mussel samples with two different PSP
      toxin standards and by calculating the recovery values for these experiments.
      These recoveries must be taken into account in order to quantify the exact amount
      of PSP toxins present in the contaminated samples.

PMID- 9580182
TI  - [Chronic obstructive lung disease in the general population. An epidemiologic
      study performed in Guipuzcoa].
AB  - To perform a cross-sectional descriptive study of chronic obstructive pulmonary
      disease in the general population. We studied 600 men aged between 40 and 60 from
      a random sample (69.9% of the total, 76.6% eligible subjects). Each subject
      answered a questionnaire, underwent spirometric testing and measurement of CO in
      expired air. Smokers accounted for 50.8% of the sample, although only 24.8% of
      the population had CO levels in expired air greater than 10 ppm. The prevalence
      of chronic bronchitis was 9.2%. Forty subjects (6.8%), only 25% of whom had
      previously undergone spirometry, met the criteria for air flow limitation. Air
      flow limitation was associated with chronic bronchitis and smoking, which were
      also mutually associated. Our data underline the need to combat smoking, given
      its relation with chronic bronchitis and airflow limitation, as well as to
      perform spirometry more routinely, mainly in smokers or patients with symptoms of
      chronic bronchitis.

PMID- 9580183
TI  - [Guidelines for nonspecific bronchial provocation tests].

PMID- 9580184
TI  - [Pulmonary hypoplasia in adults: embryology, clinical presentation and diagnostic
      methods. Our experience and review of the literature].
AB  - We report five patients diagnosed of pulmonary hypoplasia (PH) in adulthood (age
      > 18 years, range 45 to 67 years). PH was left-sided in four cases. The
      malformations found were 2 cases of renal agenesis, 2 diaphragmatic hernias and 1
      hiatal hernia. Lung function data were FEV1 0.88 +/- 0.32 L; FVC 1.30 +/- 0.52 L;
      FEV 1/FVC 68.5 +/- 5%. Arterial gases (with FiO2 0.21) were PaO2 63.6 +/- 24 and
      PaCO2 47.1 +/- 11.2 mmHg. Three cases were referred for monitoring of respiratory
      insufficiency (2 requiring home oxygen therapy) and two for radiographic study of
      chest disease. The diagnoses were made by computerized tomography (CT) of the
      chest. Congenital diseases due to underdeveloped lungs in the pseudoglandular
      phase are rarely diagnosed in adults (48 cases, including ours, have been found
      in the literature), and PH is rarely diagnosed, possibly because the anomalies
      observed are attributed to old infections. Clinical presentation is highly
      variable, depending in large measure on a history of smoking and repeated
      respiratory infections. Chest CT is at present the diagnostic tool of choice.

PMID- 9580185
TI  - [Study of the diagnostic concordance in asthma and COPD in ambulatory patients].

PMID- 9580186
TI  - Multivariate analysis of prognostic factors in resected colorectal cancer: a new
      prognostic index.
AB  - OBJECTIVE: We analysed different clinicopathological variables in colorectal
      cancer and their independent prognostic significance in order to elaborate a
      prognostic index, which may be used to categorize patients into homogeneous
      groups and indicate adjuvant therapy. DESIGN: Retrospective study. METHODS:
      Patients (n = 108) undergoing surgery for colorectal cancer were studied (5-year
      survival was controlled). Different clinicopathological variables and biological
      parameters (tumoural ploidy, proliferating cell nuclear antigen PCNA and
      nucleolar organizing regions NORs) were analysed. The Kaplan-Meier method and log
      rank test were used for univariate analysis and the Cox regression method was
      used for multivariate analysis. RESULTS: Some variables with prognostic effect in
      univariate analysis (e.g. rectal bleeding, altered bowel habit, intestinal
      obstruction, type of surgery, histological type, venous and neural invasion and
      invasive margin) did not have independent prognostic significance after Cox
      analysis. Final multivariate analysis model was defined by five parameters:
      postoperative carcinoembryonic antigen, Astler-Coller-Turnbull staging,
      histological grade, lymphatic invasion and tumour ploidy. A new prognostic index
      was elaborated that provided information to group patients in three prognostic
      categories of different risk: high, medium and low. CONCLUSION: The prognostic
      index allowed categorization of patients into different risk groups with
      identical tumoural stage and histological grade. Therefore, this index provides
      better prognostic information that may be helpful when selecting patients for
      adjuvant therapy.

PMID- 9580187
TI  - Independent cycles of exocrine pancreatic secretion, hormones and gastroduodenal
      motility in healthy fasting humans: reassessment of a complex partnership.
AB  - BACKGROUND: Interdigestive pancreatic secretion cycles in close association with
      the phases of the migrating motor complex (MMC) and release of regulatory
      hormones. The extrinsically denervated pancreas exhibits an intrinsic cyclic
      rhythm. We hypothesized that this intrinsic rhythm is normally present in the
      intact human pancreas. METHODS: 19 healthy males (age range 26-35 years) were
      studied after 12 h fasting. A manometry catheter was positioned with four
      pressure ports in the antrum and three in the duodenum, and motility was recorded
      for a complete MMC cycle or 5 h. Duodenal aspirates were sampled at 15-min
      intervals, and immediately analysed for amylase, lipase and chymotrypsin
      activities; enzyme outputs were calculated by standard marker perfusion
      techniques. Plasma levels of pancreatic polypeptide (PP) and motilin were also
      determined (RIA) at 15-min intervals. RESULTS: Output of amylase, lipase and
      chymotrypsin occurred in parallel. All phase III motility fronts were accompanied
      by a pancreatic secretory peak. However, in 12 subjects at least one secretory
      peak was observed without the concomitant occurrence of phase III. A total of 16
      out of 51 secretory peaks identified across all subjects were independent (31%).
      These phase III-independent peaks of pancreatic secretion occurred in subjects
      with a longer MMC cycle (160 +/- 19 min vs 102 +/- 13 min, P < 0.05). Phase III
      associated and -independent peaks had a similar magnitude (amylase output: 21.6
      +/- 3.9 kUh-1 vs 21.1 +/- 2.8 kUh-1, respectively). Irrespective of MMC phases,
      antral but not duodenal motor activity was closely correlated with fluctuations
      of pancreatic secretion (P < 0.05). Cycling of PP and motilin were also closely
      coordinated with pancreatic enzymes, with a particularly tight link between
      endocrine and exocrine secretion from the pancreas. CONCLUSIONS: Peaks of
      pancreatic secretion invariably occur when a phase III motor activity occurs, but
      additional secretory peaks occur without a concomitant phase III. Interdigestive
      phasic pancreatic secretion is tightly coordinated with PP and motilin release as
      well as with antral motor activity. An intrinsic rhythm of the pancreas distinct
      from other cyclic activity may be present in healthy humans, expressed as peaks
      of pancreatic secretion independent of a motor phase III.

PMID- 9580188
TI  - Erythema elevatum diutinum and AIDS: are they related?

PMID- 9580189
TI  - Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase: structure,
      catalytic mechanism and targeted inhibitor design.
AB  - The structure of the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from
      glycosomes of the parasite Trypanosoma cruzi, causative agent of Chagas' disease,
      is reported. The final model at 2.8 A includes the bound cofactor NAD+ and 90
      water molecules per monomer and resulted in an Rfactor of 20.1%, Rfree = 22.3%,
      with good geometry indicators. The structure has no ions bound at the active site
      resulting in a large change in the side chain conformation of Arg249 which as a
      consequence forms a salt bridge to Asp210 in the present structure. We propose
      that this conformational change could be important for the reaction mechanism and
      possibly a common feature of many GAPDH structures. Comparison with the human
      enzyme indicates that interfering with this salt bridge could be a new approach
      to specific inhibitor design, as the equivalent to Asp210 is a leucine in the
      mammalian enzymes.

PMID- 9580190
TI  - Neurotrophin-7: a novel member of the neurotrophin family from the zebrafish.
AB  - A novel member of the neurotrophin family, zebrafish neurotrophin-7 (zNT-7), was
      isolated from the zebrafish Danio rerio. The amino acid sequence of zNT-7 is more
      closely related to that of fish nerve growth factor (NGF) and neurotrophin-6 (NT
      6) than to that of any other neurotrophin. zNT-7 is, however, equally related to
      fish NGF and NT-6 (65% and 63% amino acid sequence identity, respectively)
      indicating that it represents a distinct neurotrophin sequence. zNT-7 contains a
      15 amino acid residue insertion in a beta-turn region in the middle of the mature
      protein. Recombinant zNT-7 was able to bind to the human p75 neurotrophin
      receptor and to induce tyrosine phosphorylation of the rat TrkA receptor tyrosine
      kinase, albeit less efficiently than rat NGF. zNT-7 did not interact with rat
      TrkB or TrkC, indicating a similar receptor specificity as NGF. We propose that a
      diversification of the NGF subfamily in the neurotrophin evolutionary tree
      occurred during the evolution of teleost fishes which resulted in the appearance
      of several additional members, such as zNT-7 and NT-6, structurally and
      functionally related to NGF.

PMID- 9580191
TI  - [Incentives for doctors from the pharmaceutical industry: ethical problems,
      limits, and alternatives].

PMID- 9580192
TI  - Delayed interval delivery in a quintuplet pregnancy.
AB  - We present a case report of delayed delivery of a quintuplet pregnancy. The
      pregnancy resulted from intrauterine insemination following hormonal treatment.
      This case may represent the first report of quintuplets delivered using the
      technique of delayed interval delivery. Three separate spontaneous labours and
      one Caesarean section for two fetuses took place between the 24th and 32nd weeks
      of pregnancy. The delay between the first and the last delivery was 61 days. Only
      a boy, born fourth, survived.

PMID- 9580193
TI  - Parental human leukocyte antigens and implantation failure after in-vitro
      fertilization.
AB  - At present, it is well accepted that maternal recognition of paternally derived
      fetal antigens occurs during normal pregnancy and may be beneficial for
      implantation and maintenance of gestation. Thus, we have investigated the
      compatibility of human leukocyte antigens (HLA) in couples with successive failed
      in-vitro fertilization (IVF) cycles. Study group 1 included 50 couples with prior
      primary infertility who had not achieved a pregnancy after > or = 3 (range 3-7,
      mean 3.7) IVF cycles where at least two embryos (mean 3.3, range 2-4) were
      transferred in each attempt. An infertile control group (group 2) included 50
      infertile couples undergoing IVF with the same indications as couples in group 1,
      who achieved a viable pregnancy with their first IVF attempt. The results were
      compared with those found in a population sample including 100 men and 100 women
      from the local population (group 3). We found a statistically significant (P <
      0.05) excess of HLA sharing (> or = 2 antigens) between partners in group 1 as
      compared to groups 2. There was a trend toward increased HLA sharing in group 1
      when groups 1 and 3 were compared. We conclude that some cases of implantation
      failure after IVF and embryo transfer might be caused by underlying close
      histocompatibility between partners.

PMID- 9580195
TI  - Chop and re-chop.

PMID- 9580194
TI  - Hemangiopericytoma of the breast: mammographic and sonographic findings.
AB  - The authors describe the mammographic and B-mode and color Doppler sonographic
      findings in a breast hemangiopericytoma in a 49-year-old woman. High vascularity
      was noted on color Doppler scans with the presence of a single vascular feeding
      pedicle. An update of the literature is included.

PMID- 9580196
TI  - [Transient radicular nerve conduction block in patients with intermittent
      neurogenic claudication].
AB  - Patients with neurogenic claudication do not usually exhibit symptoms at rest.
      The diagnosis is uncertain when there are no signs of lumbar radiculopathy.
      However, the functional deficiary could show up during a brief time at
      presentation of the symptoms if appropriate electrophysiological techniques are
      used to measure nerve conduction at the radicular segment. In 8 patients with
      neurogenic claudication, we examined the curve of recruitment of the soleus H
      reflex and in four of them the chronodispersion of the F wave of the posterior
      tibial nerve, before and after walking was also examined. Both studies showed
      normal results before walking in all patients. The H wave showed a transient
      diminution of excitability in 6 patients after walking, which lasted for a mean
      period of 7 min. Only one of these patients also showed an increase in the
      chronodispersion of the F wave. Our data suggest that conduction is transiently
      blocked in large myelinated fibers at a radicular level in patients with
      neurogenic claudication after walking. This could partially explain the symptoms
      of neurogenic claudication.

PMID- 9580197
TI  - [Recommendations on antiretroviral treatment. The AIDS Study Group of the Spanish
      Society of Infectious Diseases and Clinical Microbiology].

PMID- 9580198
TI  - Localization of adrenomedullin-like immunoreactivity in the hypothalamo
      hypophysial system of amphibians.
AB  - The presence of adrenomedullin-like immunoreactive (AMi) cell bodies and fibers
      in the hypothalamus and hypophysis of the amphibians Rana perezi (anuran) and
      Pleurodeles waltl (urodele) was examined by immunohistochemistry. A large
      population of AMi neurons was found in the suprachiasmatic nucleus of both
      species. Differently, AMi cells in the magnocellular nucleus of the preoptic area
      were only found in the urodele, whereas dispersed cells in the caudal
      infundibular region were exclusively present in the anuran. This different
      staining pattern is reflected in the hypophysis where the neural lobe is
      primarily immunoreactive in the urodele while the labeling in the intermediate
      lobe prevailed in the anuran. The results strongly suggest that, as is mammals,
      the AM in amphibians may play an important regulatory role in the hypothalamo
      hypophysial system.

PMID- 9580199
TI  - [Screening of cervical cancer, false negative smears].

PMID- 9580200
TI  - [Incidence of radicular cysts in a series of 125 chronic periapical lesions.
      Histopathologic study].
AB  - The incidence of radicular cysts in 125 chronic periapical lesions was studied in
      36 cases of periapical surgery (28.8%), and to 89 tooth extractions (71.2%).
      Histopathology revealed 18 radicular cysts (14.4%) and 107 lesions corresponding
      to chronic apical periodontitis (C.A.P.) or granulomas (85.6%). Cholesterol
      clefts, a fibrous capsule and presence of a cavity were more common in the cysts,
      significant differences being observed with respect to chronic apical
      periodontitis.

PMID- 9580201
TI  - Repercussions of acidosis on postnatal erythrocyte deformability in term and
      preterm newborns.
AB  - Erythrocyte deformability in newborns, a determining factor in neonatal blood
      hyperviscosity, is also often responsible for decreased blood flow in the
      microcirculation of several organs, such as the brain, kidneys, and digestive
      tract. In 70 neonates classified by gestational age and by the presence or
      absence of acidosis, we analyzed the filterability of erythrocytes in suspension
      through 5 polycarbonate membranes and its relation with gasometric
      determinations, Anion-GAP, plasma viscosity, plasma osmolality, erythrocyte
      volumes, and plasma lipids. Using a logistic regression analysis, controlling
      gestational age (p = 0.17), mean corpuscular volume (MCV) (p = 0.63), and mean
      corpuscular hemoglobin concentration (MCHC) (p = 0.21), the presence of acidosis
      (p = 0.0049, odds ratio: 3.60) is a risk factor for an increased rigidity index
      in newborns. Metabolic and respiratory acidosis were significantly related with
      lower erythrocyte deformability in the early neonatal period (below 5 days of
      age). Decreased plasma bicarbonate and increased Anion-GAP (even in compensated
      metabolic acidosis), as well as increased pCO2 in respiratory acidosis, were
      significantly related with decreased erythrocyte filterability. In newborns under
      32 weeks of gestational age the increase in erythrocyte rigidity index is more
      related to the low gestational age and increased MCV than to the presence of
      acidosis. These factors can produce changes in the microcirculation of these
      patients.

PMID- 9580202
TI  - Study of major volatiles in wines and discriminant analysis applied to
      classification according to region.
AB  - The major volatiles of eighty eight wines (white, rose and red) from Madrid were
      studied. The samples came from the three districts forming the "Vinos de Madrid"
      DO (Denominacion de Origen) region: Arganda, Navalcarnero and San Martin, and
      were analyzed by gas chromatography. The resulting data were treated by Stepwise
      Discriminant Analysis (SDA) in order to ascertain the efficacity of these
      compounds in classifying the wines according to their geographical origin. The
      results confirm that the above components were of little use in classifying the
      red and white wines and, although a correct classification percentage of 90.91%
      was obtained for the roses when all the variables were used, this too was
      considered unsatisfactory.

PMID- 9580203
TI  - [Biological markers of activity in chronic inflammatory bowel disease].

PMID- 9580205
TI  - [Massive rectal hemorrhage due to jejunal diverticulosis].

PMID- 9580204
TI  - [Systemic amyloidosis presenting as cholestatic jaundice].
AB  - We present a case of a 68 year old man with general deterioration and recent
      onset of jaundice that was admitted for clinical evaluation. Previous records
      were: treated bone tuberculosis, hypertrophic myocardiopathy and ischemic
      cardiopathy. Physical examination showed liver enlargement without evidence of
      chronic liver disease. Laboratory studies and other explorations such as
      abdominal ultrasound, CAT and ERCP did not leed to an objective diagnosis.
      Therefore, a liver biopsy was performed, showing liver amyloidosis AA type with
      amyloid deposits in portal spaces. The patient died three months later. The
      rarity of this clinical presentation is discussed and its poor prognosis
      outlined. Some peculiarities of liver deposits are reviewed.

PMID- 9580206
TI  - [Brain metastasis as the presenting form of esophageal adenocarcinoma].

PMID- 9580207
TI  - Fas-mediated apoptosis with normal expression of bcl-2 and p53 in lymphocytes
      from aplastic anaemia.
AB  - In order to investigate the involvement of apoptosis in the pathogenesis of
      aplastic anaemia (AA) we measured the expression of the Fas receptor (membrane
      protein that triggers apoptosis), Fas ligand (FasL), bcl-2 (cytoplasmatic protein
      that blocks apoptosis) and p53 (nuclear protein that induces apoptosis) in CD3
      and CD19 lymphocytes from the peripheral blood or bone marrow of controls,
      patients with AA, aplastic anaemia in complete remission (AA-CR) and multiply
      transfused patients without aplastic anaemia. The Fas receptor was overexpressed
      in both T and B lymphocytes from the peripheral blood and bone marrow from
      patients with AA. These abnormalities were not detected in AA-CR or multiply
      transfused patients. CD3/FasL cells were not increased and no FasL expression was
      detected in B lymphocytes. Bcl-2 was highly expressed in lymphocytes from
      controls, AA, AA-CR and multiply transfused patients (> 99% of positive cells)
      whereas p53 was not detected in any group. To further characterize the functional
      activity of the Fas receptor we performed a Fas-induced apoptosis assay in
      peripheral blood lymphocytes using an anti-Fas monoclonal antibody. The
      crosslinking of the Fas receptor transduced an increased apoptotic signal in
      lymphocytes from AA patients, but not in lymphocytes from controls, AA-CR
      patients or multiply transfused patients. Taken together, these data suggest that
      a Fas-based mediated apoptosis without the apparent participation of bcl-2 or p53
      is a possible mechanism of lymphocyte depletion in patients with AA. In addition,
      these findings suggest that Fas expression is a continuous event occurring from
      progenitor bone marrow cells to mature cells.

PMID- 9580209
TI  - [Diagnosis of meningoencephalitis caused by herpes simplex virus type 1 using
      nested PCR in CSF samples].
AB  - BACKGROUND: The aim of this study was to achieve the early diagnosis of the
      neurologic alteration caused by the Herpes Simplex virus type 1 (HSV-1) with the
      nested PCR technique in CSF. PATIENTS AND METHODS: From January, 1994 to October,
      1995, 140 CSF from 140 patients were studied in our laboratory. Ninety-five were
      diagnosed with viral meningoencephalitis (Group A) and 45 with other neurologic
      diseases (Group B). Nested PCR of HSV-1 and conventional viral cultures were
      carried out in all the cases. RESULTS: Laboratory diagnosis was achieved in 13
      (13.68%) of Group A patients: in 12 (12.63%) HSV-1 genome was detected by nested
      PCR and in one patient adenovirus was isolated. In Group B, the HSV-1 was
      detected by nested PCR in 2 patients (4.44%). CONCLUSIONS: The results obtained
      demonstrate the usefulness of nested PCR in HSV-1 infection for the diagnosis of
      herpetic meningoencephalitis in initial stages of the disease, from a single CSF
      sample.

PMID- 9580208
TI  - The C(H)1 domain of IgG is not essential for C3 covalent binding: importance of
      the other constant domains as targets for C3.
AB  - The covalent binding of C3 to antigen-antibody complexes [immune complexes (IC)]
      plays a pivotal role in the elimination of antigens. C3 prevents the formation of
      large IC lattices promoting their solubilization. Subsequently, bound C3
      fragments determine the efficacy of antigen presentation, and the generation of
      antibody responses and immunological memory. C3 binding to IgG-IC generates IgG
      C3b-C3b complexes which are detected by SDS-PAGE as two major bands: C3alpha65
      heavy chain and C3alpha65-C3alpha43 covalent complexes. Using human heat
      aggregated IgG1 as a model of IC, a C3b binding site was localized only in the
      Cgamma1 domain. However, with true IC of ovalbumin and rabbit IgG anti-ovalbumin,
      C3b binds to both the Fab and Fc regions of IgG. To study the binding of C3b to
      the different domains of IgG and particularly to evaluate the involvement of the
      Cgamma1 domain, we have constructed recombinant single-chain antibodies without
      Cgamma1, which have the structure: V(H)-linker-V(L)-hinge-Cgamma2-Cgamma3 (scAb).
      The variable domains were from a mouse mAb anti-HSA and the constant region
      (hinge-C(H)2-C(H)3) from human IgG1 or rabbit IgG. C3 binds very efficiently to
      IC formed with human (h-scAb) or rabbit (r-scAb) recombinant antibodies (scAb
      HSA) and generates also two bands on SDS-PAGE (C3alpha65-scAb and C3alpha65
      C3alpha43), which are the counterparts of those of the complete antibody. In
      addition, IC formed with scAb activate the alternative pathway to a similar
      extent as IC of the entire IgG. These data indicate that the Cgamma1 domain is a
      dispensable region for C3b binding and that the remaining constant domains are as
      efficient as Cgamma1 in C3b binding. Overall these results support the view that
      C3 does not specifically recognize a unique site in the Cgamma1 domain. Rather it
      seems to be able to attach along the antibody molecule. Probably this implies an
      advantage for effective processing of C3b-IC and elimination of antigens in vivo.

PMID- 9580210
TI  - [Dermatophytes isolated in our clinics. 5-year-study in Zaragoza].
AB  - BACKGROUND: This review summarizes the different species of dermatophytes
      isolates in our laboratory between 1991 and 1995. We describe the clinical forms
      and establish the distribution over this period of time. METHODS: Retrospective
      survey of samples from outpatients of the Dermatology Service in Miguel Servet
      Hospital where mycologic cultures are required. The extraction of samples is made
      by scrapes with a carpet or scalpel and they are cultured on Saboureaud agar with
      chloramphenicol and dermatophytes agar for 3 weeks. All plates were incubated at
      28 degrees C. The identification of isolated strains is made by means of
      morphologic and physiologic criteria; the doubtful strains were identified in
      national referral center of Majadahonda CNMVISS. RESULTS: 4004 samples were
      analyzed from 3934 patients and 543 strains of dermatophytes were isolated. The
      frequencies were as follow: Microsporum canis (44%), Trichophyton mentagrophytes
      (31.4%), Trichophyton rubrum (18.6%), Epidermophyton floccosum (2.6%),
      Microsporum gypseum (1.4%), Trichophyton tonsurans (0.7%), Trichophyton
      verrucosum (0.7%), Trichophyton violaceum (0.2%) y Microsporum audouinii (0.2%).
      The most frequently observed dermatophytoses were Tinea corporis (54.8%),
      followed by Tinea unguium (12.6%), Tinea capitis (12.5%), Tinea pedis (8.3%),
      Tinea manuum (6.3%), Tinea cruris (4.7%) and Tinea barbae (0.7%). CONCLUSIONS:
      The zoophylic species are the most prevalent in our area and we have observed a
      raise of Microsporum canis in recent years. It is important to perform mycologic
      survey in every suspected lesion in older to determinate the true incidence of
      human dermatophytoses.

PMID- 9580211
TI  - Routine detection of point mutations in non-classic steroid 21-hydroxylase.

PMID- 9580212
TI  - Snapshots of nutrition and dietetics outside of the United States: The
      Netherlands and Colombia.

PMID- 9580213
TI  - Trends in cancer mortality in Argentina, 1966-91.
AB  - Trends in death certification rates for 12 major cancer sites and total cancer
      mortality in Argentina were analysed for the period 1966-91 on the basis of the
      World Health Organization database. In the late 1960s, total cancer mortality
      rates in Argentina (184/100,000 men, 117/100,000 women, world standard) were
      among the highest in the world. Over the 25-year period considered, however,
      cancer mortality in Argentina declined by 15% in both sexes, to reach 157/100,000
      in men and 99/100,000 in women, for 1990-91. These rates were somewhat lower than
      those of North America and, particularly for women, relatively low on a worldwide
      scale. The favourable trends, observed mostly between the 1960s and the 1980s,
      reflect the steady decline in gastric cancer rates in both sexes, together with
      some decline in oesophageal, lung and other tobacco-related neoplasms, mostly in
      men, following some decline in tobacco consumption over the last two decades. The
      fall in oesophageal cancer may be related to decreased consumption of hot mate,
      too. Colorectal cancer rates were high in the 1960s, but declined by 17% in men
      and 35% in women. An approximately 50% decline was observed for skin cancer
      mortality, which was among the lowest in the world in the early 1990s, and some
      decline was observed also for leukaemias and uterine cancer, while breast and
      prostate neoplasms showed a general stability. The two major unfavourable
      features of cancer mortality in Argentina were the persistently high rates for
      oesophageal in men, and for uterine cancer mortality in women. These are likely a
      result of hot mate drinking for oesophageal cancer and inadequate screening for
      cervical cancer.

PMID- 9580214
TI  - Organization of the caudal rhombencephalic alar plate of the ribbed newt
      Pleurodeles waltl: evidence for the presence of dorsal column and lateral
      cervical nuclei.
AB  - As part of a recent program on the evolution of somatosensory systems in
      vertebrates, the cytoarchitecture, chemoarchitecture, and fiber connections of
      the caudal rhombencephalic alar plate were studied in the ribbed newt,
      Pleurodeles waltl. This part of the brain stem includes ill-defined dorsal column
      and lateral cervical nuclei. A cytoarchitectonic analysis revealed that the
      caudal medullary alar plate consists of an inner and an outer cell layer. The
      dorsomedial part of the outer cell layer at the obex level contains the dorsal
      column nucleus (DCN), whereas its ventrolateral part constitutes the lateral
      cervical nucleus (LCN). NADPH-diaphorase histochemistry and calbindin D-28k
      immunohistochemistry clearly delineate the main components of the compact inner
      cell layer, i.e. the nucleus of the solitary tract dorsally and the nucleus of
      the descending trigeminal tract ventrally. Neither NADPH-diaphorase-labeled nor
      calbindin D-28k positive neurons were observed in the DCN and LCN. With
      anterograde and retrograde tracing, the DCN and LCN were further delineated.
      Labeling of ascending dorsal root projections showed that the dorsal column and
      the DCN are somatotopically arranged: lumbar primary afferent fibers terminate on
      medial DCN neurons, whereas cervical primary afferent fibers terminate on lateral
      DCN neurons. The LCN is densely innervated by the dorsolateral funiculus.
      Retrograde tracing showed extensive, predominantly contralateral projections of
      both the DCN and LCN to the torus semicircularis and the ventral thalamus. These
      data show that even in the poorly segregated caudal rhombencephalic alar plate of
      urodeles a DCN and LCN can be distinguished with afferent and efferent
      projections comparable to those in anurans and other terrestrial vertebrates.

PMID- 9580215
TI  - Neuropeptides in the cat amygdala.
AB  - The distribution of seven neuropeptides was studied in the cat amygdala using an
      indirect immunoperoxidase technique. No labeling was found for luteinizing
      hormone-releasing hormone or beta-endorphin (1-27). Sparse alpha-melanocyte
      stimulating hormone-immunoreactive fibers were found in the basomedial nucleus of
      the amygdala, whereas a low density of fibers containing alpha-neo-endorphin was
      observed in the anterior amygdaloid area. Neurotensin was observed in fibers of
      the anterior amygdaloid area (low density) and both the lateral (low density) and
      the medial part (moderate density) of the central nucleus. A low density of
      fibers containing neurokinin A was found in the anterior amygdaloid area, the
      basolateral nucleus, and the medial part of the central nucleus. A moderate
      density was observed in the basomedial nucleus and in the medial and cortical
      nuclei. Fibers containing somatostatin-28 (fragment 1-12) were observed in all
      the amygdaloid nuclei, whereas immunoreactive cell bodies were found in all the
      nuclei except in the medial part of the central nucleus and the medial nucleus.
      Perikarya containing neurokinin A were observed in the latter nucleus. The
      results point to a discrete distribution of peptidergic fibers in the cat
      amygdala, as well as the occurrence of neurons containing neurokinin A and
      somatostatin-28 (fragment 1-12). The distribution of the peptides studied in the
      cat is compared with the location of the same peptides in the amygdala of other
      species. The possible diencephalic origin of the peptidergic fibers is also
      discussed.

PMID- 9580216
TI  - Sequential changes of energy metabolism and mitochondrial function in myocardial
      infarction induced by isoproterenol in rats: a long-term and integrative study.
AB  - Acute myocardial infarction is the second cause of mortality in most countries,
      therefore, it is important to know the evolution and sequence of the
      physiological and biochemical changes involved in this pathology. This study
      attempts to integrate these changes and to correlate them in a long-term model
      (96 h) of isoproterenol-induced myocardial cell damage in the rat. We achieved an
      infarct-like damage in the apex region of the left ventricle, occurring 12-24 h
      after isoproterenol administration. The lesion was defined by histological
      criteria, continuous telemetric ECG recordings, and the increase in serum marker
      enzymes, specific for myocardial damage. A distinction is made among
      preinfarction, infarction, and postinfarction. Three minutes after drug
      administration, there was a 60% increase in heart rate and a lowering of blood
      pressure, resulting possibly in a functional ischemia. Ultrastructural changes
      and mitochondrial swelling were evident from the first hour of treatment, but
      functional alterations in isolated mitochondria, such as decreases in oxygen
      consumption, respiratory quotient, ATP synthesis, and membrane potential, were
      noticed only 6 h after drug administration and lasted until 72 h later.
      Mitochondrial proteins decreased after 3 h of treatment, reaching almost a 50%
      diminution, which was maintained during the whole study. An energy imbalance,
      reflected by a decrease in energy charge and in the creatine phosphate/creatine
      ratio, was observed after 30 min of treatment; however, ATP and total adenine
      nucleotides diminished clearly only after 3 h of treatment. All these alterations
      reached a maximum at the onset of infarction and were accompanied by damage to
      the myocardial function, drastically decreasing left ventricular pressure and
      shortening the atrioventricular interval. During postinfarction, a partial
      recovery of energy charge, creatine phosphate/creatine ratio, membrane potential,
      and myocardial function occurred, but not of mitochondrial oxygen consumption,
      rate of ATP synthesis, total adenine nucleotides, or mitochondrial proteins.
      Interesting correlations of the sequential changes in heart and mitochondrial
      functions with energy metabolism were obtained at different stages of the
      isoproterenol-induced cardiotoxicity. These correlations could be useful to study
      and understand the cellular events involved in this pathology.

PMID- 9580217
TI  - A peptide of nine amino acid residues from alpha-sarcin cytotoxin is a membrane
      perturbing structure.
AB  - A water-soluble synthetic peptide with only nine amino acid residues, comprising
      the 131-139 sequence region of the cytotoxic protein alpha-sarcin (secreted by
      the mold Aspergillus giganteus), interacts with large unilamellar vesicles
      composed of acid phospholipids. It promotes lipid mixing between bilayers and
      leakage of vesicle aqueous contents, and it also abolishes the phospholipid phase
      transition. Other larger peptides containing such an amino acid sequence also
      produce these effects. These peptides acquire alpha-helical conformation in the
      presence of trifluoroethanol, but display beta-strand conformation in the
      presence of sodium dodecyl sulfate. The interaction of these peptides with the
      lipid vesicles also results in beta-structure. The obtained data are discussed in
      terms of the involvement of the 131-139 stretch of alpha-sarcin in its
      interaction with lipid membranes.

PMID- 9580218
TI  - Effects of capture and transport on blood parameters in free-ranging mouflon
      (Ovis ammon).
AB  - Twelve free-ranging mouflon (Ovis ammon), eight adults and four lambs, were
      captured in northeast Spain. The animals were transported for 9 hr from the
      capture site to the Wildlife Rescue Center at Vallcalent (Lleida), 300 km SW.
      Blood samples were taken at capture and after transport to study the effects on
      hematologic and biochemical parameters. The RBC, PCV, Hb, and alkaline
      phosphatase values were significantly higher in lambs than in adults, and total
      protein levels were significantly lower in lambs. Comparisons of blood parameters
      of adult animals at capture and after transport revealed significantly lower RBC,
      PCV, Hb, PLT, lymphocyte counts, glucose, cholesterol, creatinine, and alkaline
      phosphatase values and significantly higher neutrophil count, AST, ALT, CK, LDH,
      and total bilirubin levels after transport. The differences observed in the blood
      parameters of lambs before and after transport were not statistically
      significant.

PMID- 9580219
TI  - Osmolarity modulates the expression of the Hha protein from Escherichia coli.
AB  - The effect of the osmolarity of the culture medium on the expression of the hha
      gene of Escherichia coli was investigated. When cells were grown in LB medium,
      expression reached a maximum in the exponential phase of growth and decreased in
      the stationary phase. Increasing the osmolarity of the LB medium had no
      significant effect on the expression of the hha gene, but depletion of NaCl led
      to a significant decrease in expression. Expression of the hha gene is thus
      sensitive to the osmolarity of the growth medium. High levels of expression of
      the hha gene when cells are grown at medium to high osmolarity are consistent
      with the finding that the Hha protein appears to play its main modulatory role
      when cells grow under these conditions.

PMID- 9580220
TI  - [Analgesic-antispasmodic effect and safety of lysine clonixinate and L
      hyoscinbutylbromide in the treatment of dysmenorrhea].
AB  - The purpose of this longitudinal open but not comparative study was to confirm
      the safety and efficacy of Lysine clonixinate (125 mg) and hyoscinbutylbromide
      (10 mg) capsules, during a period of observation of there menstrual cycles on 30
      women with uterine dysfunction due to primary or secondary dysmenorrhea. The time
      of evolution for primary dysmenorrhea was of 4.46 years, and for secondary was of
      1.77 years. Some associated manifestations of dysmenorrhea were: nausea (92%),
      vomit (92%), general pain (82.1%), abdominal pain (85.7%) and headache (46.4%).
      Regarding to the menstrual pain intensity, at first was highly severe in 10.7%
      severe in 42.9%, and moderate in 46.4%. At the end of the study, only 1 of 28
      patients showed menstrual pain of moderate intensity. Only three adverse effects
      of light intensity were found without needing treatment, related to the
      manifestations of gastralgia and sleepiness. The association of a spasmolytic
      analgesic (Lysine clonixinate and hyoscinbutylbromide bromide) on the treatment
      for primary or secondary dysmenorrhea, reduces and prevents the menstrual pain
      (colic) as well as the associated manifestations with few spasmolytic association
      is efficacy and safety.

PMID- 9580221
TI  - Promotion of development of bovine embryos produced in vitro by addition of
      cysteine and beta-mercaptoethanol to a chemically defined culture system.
AB  - The aim of this research was to determine the effects of L-cysteine and beta
      mercaptoethanol on the in vitro development of bovine embryos that had been
      produced in vitro. A 2 x 3 factorial arrangement of treatments was used to
      evaluate the effect of 0.63 or 6.9 microM L-cysteine and 0, 10, or 100 microM
      beta-mercaptoethanol on the development of bovine embryos in a chemically defined
      medium. Embryos containing 6 to 8 cells were randomly allocated to one of the six
      treatment combinations and were cultured for 7 d. Both beta-mercaptoethanol and L
      cysteine increased the number of embryos that reached the blastocyst stage of
      development, although no interaction was observed between the compounds. Embryos
      that were cultured in the presence of beta-mercaptoethanol had more cells at the
      blastocyst stage than did embryos cultured in medium without beta
      mercaptoethanol. These findings provide evidence that beta-mercaptoethanol and L
      cysteine promote increased embryonic development and that beta-mercaptoethanol
      increases the number of cells in bovine embryos produced in vitro and cultured in
      a cell-free, protein-free culture system.

PMID- 9580222
TI  - Jugular venous oxygen monitoring: a helpful technique in the early diagnosis of a
      traumatic carotid-cavernous sinus fistula.
AB  - This report describes the early diagnosis of a right traumatic carotid-cavernous
      sinus fistula (CCSF) in a patient with head injury manifested as an acute
      increase in right jugular venous oxygen saturation and with no ophthalmic
      clinical signs. High values of jugular venous oxygen saturation must be
      cautiously interpreted with the clinical examination and computed tomographic
      findings to establish an accurate diagnosis of hyperemia with or without a CCSF.

PMID- 9580223
TI  - Characterization and trypanocidal activity of nifurtimox-containing and empty
      nanoparticles of polyethylcyanoacrylates.
AB  - The aim of this study was to evaluate the utility of nanoparticles of
      polyalkylcyanoacrylate as a targeted delivery system for nifurtimox against
      Trypanosoma cruzi, responsible for Chagas' disease. Ethylcyanoacrylate
      nanoparticles were prepared by an emulsion polymerization process and
      formulations containing different concentrations of nifurtimox,
      polyethylcyanoacrylates and surfactants were investigated and analysed for size
      and drug content. The nanoparticles obtained were less than 200 nm in size, as
      measured by electron microscopy and cytometry. The peak percentage of nifurtimox
      uptake into the nanoparticles was 33.4% for use of 500 microL
      polyethylcyanoacrylate, 200 microL surfactant (Tween 20) and 10 mg nifurtimox in
      50 mL polymerization medium. The highest release of nifurtimox from the
      nanoparticles was 65.4% after 6-h incubation at pH 7.4. In-vitro studies using
      cultures of T. cruzi epimastigotes revealed considerably increased trypanocidal
      activity compared with a standard solution of nifurtimox. Studies of cell
      cultures previously infected with metacyclic forms of the parasite showed that
      only 2-h treatment with solutions of 0.001% of the nanoparticle suspension
      reduced parasitism by 87-94% both when the nanoparticles were loaded with
      nifurtimox and when unloaded. Electron-microscopic examination revealed processes
      of degeneration and lysis, suggesting apoptotic processes, in intracellular
      amastigotes and free amastigotes treated with the nanoparticles. It was
      demonstrated that unloaded nanoparticles, by mechanisms not completely
      elucidated, have trypanocide activity similar to that of a standard solution of
      nifurtimox. It is concluded that the nanoparticles loaded with nifurtimox
      constitutes a good carrier of the drug against T. cruzi. The loaded-nanoparticles
      significantly increase trypanocidal activity.

PMID- 9580224
TI  - Polyamine-mediated heart hypertrophy induced by clenbuterol in the mouse.
AB  - The use of beta-agonists as growth-promoting agents in cattle could lead to toxic
      side-effects in man. One such effect is the accumulation of polyamines which seem
      to be implicated in muscle and heart hypertrophy. We have studied the induction
      of cardiac hypertrophy after treatment with clenbuterol and the role of
      polyamines in this effect. Treatment of mice with repeated doses of clenbuterol,
      a specific beta-adrenergic agonist, resulted in a marked increase in heart muscle
      weight whereas total body weight did not change significantly. Clenbuterol-linked
      cardiac hypertrophy could be prevented by co-administration of either the non
      specific beta-adrenergic antagonist, propranolol, or the irreversible inhibitor
      of ornithine decarboxylase, alpha-difluoromethylornithine. The clenbuterol
      induced cardiac hypertrophy was associated with a corresponding increase in the
      level of the polyamines putrescine, spermidine and spermine. These observations
      are indicative of the role of polyamines in cardiac hypertrophy induced by
      clenbuterol.

PMID- 9580225
TI  - Associated factors to psychiatric morbidity in postmenopausal phases.
AB  - BACKGROUND: The greatest risk of psychiatric morbidity during the climacteric
      years is linked to a greater exposure to stressful life experiences, women's
      dissatisfaction with their role in society and to an absence of social backup.
      The question to be posed now is the extent to which the longitudinal surveys can
      confirm, refute or complement the results of the cross-sectional analyses.
      METHODS: A study involving population-based cohorts was carried out on a sample
      of 120 women who had been previously identified as being premenopausal or
      menopausal during a cross-sectional examination conducted between 1987 and 1988
      within the city of Valencia (Spain). The aims were to analyze the movements of
      specific psychosocial factors (role satisfaction, level of social support) making
      a comparison between the premenopausal and postmenopausal phases. RESULTS: An
      increase in the frequency of psychiatric episodes was detected in the later
      stages of the climacteric. The absence of global social support, being a possible
      psychiatric case and experiencing severe life events during the initial phases of
      the climacteric all emerge as being the most reliable factors for predicting the
      psychiatric morbidity during the postmenopausal phase. CONCLUSIONS: The results
      lend weight to the hypothesis of psychiatric morbidity being linked to social
      changes. A discussion of the clinical implications is presented.

PMID- 9580226
TI  - Genotoxicity testing of methyl tertiary-butyl ether (MTBE) in the Salmonella
      microsuspension assay and mouse bone marrow micronucleus test.
AB  - Methyl tertiary-butyl ether (MTBE) is an oxygenated fuel additive that is present
      in gasoline at levels up to 15% by volume. Since the 1990 Clean Air Act
      amendments require the use of oxygenated gasoline in 39 areas of the USA, the use
      of MTBE is projected to continue to dramatically increase. As the use of MTBE
      increase, the potential for environmental release of MTBE from gasoline stations
      and automobiles will also increase. Despite its growing use as a fuel additive
      and its potential for increased exposure to the public, few genotoxicity data on
      MTBE have been published in the peer-review literature. In the present study, we
      tested the potential genotoxicity of MTBE in two short-term test systems, an in
      vitro Salmonella microsuspension assay and an in vivo mouse bone marrow
      micronucleus test. For the microsuspension assay, MTBE was tested at 7 dose
      levels of 30 to 7400 micrograms/tube in tester strain TA98, TA100, TA104, and
      TA1535, with and without the addition of metabolic enzymes (S9) at 4
      concentration (0, 300, 600, and 1200 micrograms S9/ml final concentration). A
      closed system was used to minimize loss of MTBE. The response was not
      significant. However, a high degree of toxicity was observed at the highest doses
      in all tester strains. MTBE was also tested for clastogenicity i the mouse bone
      marrow micronucleus test using both male and female Swiss-Webster mice. Mice were
      administered single intraperitoneal injections of MTBE in olive oil at 5 doses
      ranging from 0.25 to 1.75 g/kg. There were no significant increases in
      micronucleus formation at any dose of MTBE when compared with the negative
      control animals receiving only olive oil. MTBE was not positive when tested for
      point mutations and clastogenicity, using respectively, a Salmonella
      microsuspension assay and the mouse bone marrow micronucleus test.

PMID- 9580227
TI  - Late rupture of the renal graft: not always graft rejection.

PMID- 9580228
TI  - p21WAF1 mutation is not a predominant alteration in pediatric bone tumors.
AB  - The molecular events leading to the development of pediatric bone tumors are not
      clear to date, but abnormal cell cycle progression has been reported in a wide
      variety of human tumors due to the alteration of several tumor suppressor genes.
      We have analyzed 55 bone sarcoma samples from pediatric patients to test the
      possibility that they harbor mutations in the p21WAF1 tumor suppressor gene.
      Mutation analysis was performed through denaturing gradient gel electrophoresis
      analysis of exon 2 of the gene and consequent cycle sequencing of the altered
      fragments. No mutations affecting the coding regions of the p21WAF1 were found.
      Nevertheless, we found genetic polymorphisms in nine of the samples analyzed. We
      conclude that p21WAF1 mutations do not play an important role in the development
      of this kind of pediatric malignancy.

PMID- 9580229
TI  - Regional tongue sensitivity for sweetness and pungency of ethanol-aspartame
      mixtures.
AB  - Binary mixtures of aspartame prepared at three levels of concentration and
      dissolved in four ethanolic dilutions were perceptually evaluated. Sweet-pungent
      combinations were presented in solution or in disks of filter paper (paper)
      soaked in the solutions. Variations in sweetness and pungency were examined at
      two oral loci including the tip and the back plus the front of the tongue in the
      liquid condition or the tip and the back of the tongue in the paper condition. A
      similar behavior was observed in liquid and paper conditions; as the
      concentration of aspartame and ethanol increased so did the intensity for sweet
      and pungent qualities. Whereas sweetness was not influenced by ethanol addition
      (2-8% V/V), a suppressive effect of aspartame (1-4 mM) on pungency was noted for
      liquid but not for the paper condition. Sweetness was enhanced when the back plus
      the front of the tongue was stimulated by solutions. Finally, there was a complex
      pattern of regional effects on the perceived pungency of alcoholic-sweet
      solutions that was not replicated in the paper condition.

PMID- 9580230
TI  - [Improvement in diastolic function in hypertensive patients with left ventricular
      hypertrophy with inhibitors of the angiotensin converting enzyme].
AB  - An open and multicentric study was conducted with 66 patients with mild to severe
      diastolic arterial hypertension and echocardiographic left ventricular
      hypertrophy, the evolution of diastolic function, by means of doppler transmitral
      flow echocardiography, under treatment with ramipril, an angiotensin converting
      enzyme inhibitor, at a dose of 2.5 and 5 mg/day, or combined with a diuretic,
      after three and six months of treatment. Despite not obtaining the tensional
      control in all patients, a decrease in the mass, both in absolute values and mass
      index, was obtained. This decrease was observed both in male and female patients
      from the first three months, which went on until the sixth month, thus suggesting
      an independent action of the hemodynamic load decrease for the obtention of this
      effect. There was also a change in the ventricular geometry with a displacement
      of patients from concentric enlargement to normal, remodelling and eccentric
      enlargement. The diastolic function improved both for the early and for the late
      maximal filling velocity, relationship between both, and deceleration time,
      although the time during which this improvement occurred was different for each
      parameter, thus indicating the different influence of the dynamic and structural
      factors on these parameters. No correlation was found between the improvement in
      diastolic function and hypertrophy regression. We can conclude that ramipril is
      useful for the control of the left ventricular hypertrophy and diastolic
      function, irrespective of arterial tension values.

PMID- 9580231
TI  - [Acute pancreatitis and thrombotic thrombocytopenic purpura].

PMID- 9580232
TI  - [Prevalence of hepatitis D in a population of Northeast Mexico and its
      relationship with other viruses].
AB  - BACKGROUND: There are few reports in Mexico on the prevalence of infection by
      virus D. OBJECTIVE: The aim of the present study was to study the hepatitis D
      virus infection prevalence in patients entering to the University Hospital.
      METHODS: Seventy three HBsAg positive patients sera were studied. There were 38
      patients with acute hepatitis, 28 patients with chronic liver disease and 7 were
      asymptomatic HBsAg carriers. Serological markers for hepatitis viruses B, D and C
      were detected by means of ELISA test (Abbott). RESULTS: Anti-HDV was detected in
      3 cases (4%). The first two cases were men with acute hepatitis B. Both had a
      coinfection by viruses B and D, however IgM anticore could not be demonstrated in
      the first case, this patient developed hepatic cirrhosis within 13 months, in
      addition he had a concurrent infection by hepatitis C virus with a positive
      second generation ELISA antibody. The second case recovered from the acute
      hepatitis. The third case was a female nurse with acute hepatitis and a
      coinfection by viruses B and D who recovered from the acute attack. Antibody to
      hepatitis C was present in 3 out of 22 patients with chronic liver disease
      (13.6%), one of them having an hepatocellular carcinoma. CONCLUSIONS: Our results
      coincide with the previously reported low incidence of hepatitis D and represent
      the first report in Mexico of concurrent infections by viruses B-C and B-D-C.

PMID- 9580233
TI  - [Malnutrition and total parenteral nutrition: a cohort study to determine the
      incidence of refeeding syndrome].
AB  - The Refeeding Syndrome is conformed by a series of clinical manifestations
      related to electrolytic alterations associated with the restarting of the
      nutritive contribution both enteral and parenteral. AIM: To detect the Refeeding
      Syndrome incidence in malnourished patients who required nutritional, enteral or
      endovenous support and its relationship with mortality. MATERIAL AND METHODS: A
      cohort study was performed in the service of Nutritional Support of the IMSS
      (Social Security Mexican Institute) Specialties Hospital CMN Leon, from June 1995
      to May 1996. All patients with mild and severe malnutrition were included, they
      received endovenous or enteral nutritious support for more than 7 days, without
      presenting previous electrolytic unbalance. Serum potassium, phosphorous, and
      magnesium levels were determined before starting the nutritious support and also
      on the 3rd, 7th, and 10th days. Descriptive statistics, Student's t and Z test
      were used, with a 5% significance level. RESULTS: 148 patients with total
      nutritional support, 23 (16%) of them with restrained malnutrition and 65 (44%)
      with severe deficit. 54 men and 34 women with an average age of 51.6 +/- 19.4
      years. Nineteen patients were eliminated due to a nutrition period of less than 7
      days, and other 19 were also eliminated for presenting electrolytic alterations
      before the nutritive support started. An incidence of 48% of electrolytic
      alterations compatible with the refeeding syndrome was the result in the
      remaining 50 patients. The alterations were: hypomagnesemia 13/24, hypokalemia
      12/24 and hypophosphatemia 4/24; in 55% of the cases the syndrome appeared at the
      third day of administration. Hospital sojourn of patients with the syndrome was
      26.7 +/- 18 days vs 15.3 +/- 7 (p < 0.05) of those who did not present it. 15
      patients died, 5 of them had electrolytic alterations before nutrition, 7 (29%)
      with refeeding syndrome and 3 (12%) did not presented it (p = 0.059).
      CONCLUSIONS: Refeeding Syndrome is a frequent entity in malnourished patients
      submitted to enteral or parenteral nutrition; at least in this study it was of
      48%; its presence was followed by a longer hospital stay and a higher mortality
      rate.

PMID- 9580234
TI  - [Effects of fiber administration in the prevention of gallstones in obese
      patients on a reducing diet. A clinical trial].
AB  - Nearly 30% of the obese patients treated with hypoenergetic diets for weight
      reduction develop gallstone disease (GD). Until the present time, the use of
      ursodeoxycholic acid (UDA) is the only available therapeutic measure to avoid the
      development of GD. Dietary fiber induce a bile acid synthesis. A double-blind
      clinical trial was conducted to compare the effect of rational diet plus UDA vs a
      rational diet supplemented with Psyllium plantago (Pp) for the prevention of GD
      in obese subjects undergoing a weight-reduction diet. Patients with a body mass
      index (BMI = weight in Kg/square height in m) of 30 Kg/m2 or more and with normal
      gallbladder and biliary tree ultrasound (GBUS) were included. Weight-reduction
      diets were individually calculated for each patient according to their energy
      expenditure (EE). Patients were randomly and blindly assigned either to group I
      (diet + 750 mg UDA + fiber placebo) or group II (diet + 15 g Pp+ UDA placebo). An
      anthropometric evaluation was performed to each patient before and after the two
      month treatment, as well as resting EE by indirect calorimetry, GBUS and
      endoscopy for the determination of cholesterol crystals in duodenal bile. Weight
      reduction was similar in both groups (group I = 6 +/- 2 Kg vs group II = 6 +/- 3
      Kg). GD development was observed in one patient of group I (5.5%) and two
      patients of group II (p > 0.05). All patients with GD lost a minimum of 4 Kg
      during the study period. GD development did not correlate with the presence of
      crystals in the duodenal bile at the beginning of the study. Our results suggest
      a beneficial effect of a rational diet with fiber supplementation to prevent GD
      development in obese patients included in a weight reduction program.

PMID- 9580235
TI  - [Meckel's diverticulum in adults. A 3-decade experience].
AB  - OBJECTIVE: To review the prevalence, clinic manifestations and characteristics of
      the adult Meckel's diverticulum in the Hospital Espanol de Mexico. BACKGROUND:
      The Meckel's diverticulum is the most frequent congenital malformation of the
      gastrointestinal tract. However, only in seldom occasions produces manifestations
      in adults. METHODS: Retrospective review of 31 years. RESULTS: Meckel's
      diverticulum was found in only 13 cases. The most common clinical manifestation
      was pain in the right lower abdominal quadrant; there was not a single case of
      bleeding. A correct pre surgical diagnosis was done in only one patients. Post
      surgical course was satisfactory in all patients. CONCLUSION: In adults, the
      Meckel's diverticulum complications are uncommon, being the most frequent
      clinical manifestation the pain in the right lower abdominal quadrant and
      intestinal obstruction.

PMID- 9580236
TI  - Collateral blood supply through the ophthalmic artery: a steal phenomenon
      analyzed by color Doppler imaging.
AB  - OBJECTIVE: This study aimed to evaluate the retrobulbar circulatory effects of
      reversed ophthalmic artery flow (ROAF) on the ophthalmic artery branches by means
      of color Doppler imaging. DESIGN: The design was a case-controlled study.
      PARTICIPANTS: Among 56 consecutive patients with severe (>70% stenosis) occlusive
      carotid artery disease, 15 patients (26.8%) with ROAF were identified. The
      control group consisted of 15 patients with similar degrees of carotid artery
      stenosis and forward ophthalmic artery flow. INTERVENTION: Arteriography and
      measurement of the retrobulbar hemodynamic parameters with color Doppler imaging
      were performed. MAIN OUTCOME MEASURES: Blood flow velocities and resistive index
      in the ophthalmic, central retinal, and temporal short posterior ciliary arteries
      were measured. RESULTS: Arteriography confirmed the diagnosis of ROAF in all 15
      patients. There was no patient with ROAF diagnosed by arteriography and not
      diagnosed by color Doppler imaging. The frequency of bilateral severe occlusive
      carotid artery disease was significantly higher in the ROAF group (40%) compared
      to the control group (6.6%) (P = 0.04). Patients with ROAF showed significantly
      reduced vascular resistance in the ophthalmic artery (P = 0.03), higher vascular
      resistance, and lower blood flow velocities in the central retinal and temporal
      short posterior ciliary arteries (P < 0.05). CONCLUSION: This study suggests that
      patients with ROAF show a steal phenomenon, characterized by a shunt to the low
      resistance intracranial circuit and reduction of retrobulbar blood flow.

PMID- 9580237
TI  - Effects of a self-etching primer on enamel shear bond strengths and SEM
      morphology.
AB  - PURPOSE: To study a dental adhesive system containing a self-etching primer, by
      evaluating the enamel shear bond strengths and comparing the SEM interfacial
      morphology. MATERIALS AND METHODS: 100 flat enamel bonding sites were prepared to
      600-grit on proximal surfaces of caries-free human molars. The bonding surfaces
      were treated with Clearfil Liner Bond 2 as recommended by the manufacturer, or
      combined with various acidic etchants. A composite rod (Clearfil Photo Anterior)
      was applied to the bonding area in two increments in a Teflon mold and
      polymerized for 100 s. After 24 h of water storage, the specimens were
      thermocycled and the shear bond strengths measured using an Instron testing
      machine. Forty extra molar crowns were roughened and treated with Clearfil Liner
      Bond 2 and alternative etchants, as described. A low-viscosity resin was bonded
      to the occlusal surfaces of these crowns, which were further demineralized and
      deproteinized. Field-Emission SEM examinations were carried out to evaluate the
      effects of different treatments on enamel surfaces. RESULTS: The mean shear bond
      strengths were in the range of 18.1 MPa to 25.9 MPa, without significant
      differences between pairs of means. The failures were predominantly of the
      adhesive type. The use of alternative etchants resulted in the deepest etching
      patterns. The use of Clearfil Liner Bond 2, according to manufacturer's
      directions, resulted in a poorly-defined etching pattern. Regardless of the
      alternative etchant used, the use of the self-etching primer did not affect the
      mean enamel shear bond strength.

PMID- 9580238
TI  - Bond strengths and SEM morphology of dentin-amalgam adhesives.
AB  - PURPOSE: To compare two one-bottle dentin bonding systems (DBS) with five multi
      bottle DBS and one resin-modified glass-ionomer cement, regarding their ability
      to bond spherical amalgam to freshly prepared dentin surfaces, in vitro. The
      tested hypothesis was that one-bottle DBS would result in lower shear bond
      strengths than multi-bottle DBS. MATERIALS AND METHODS: Eighty flat dentin
      bonding sites were prepared to 600-grit on middle dentin of caries-free human
      molars mounted in acrylic resin. The bonding surfaces were treated with eight
      different bonding systems, according to manufacturer's instructions: All-Bond 2;
      Amalgambond Plus; Fuji Duet; One-Step/Resinomer; OptiBond; OptiBond FL; Prime &
      Bond 2.0/Dyract Cem; and Scotchbond Multi-Purpose Plus. A spherical amalgam alloy
      (Megalloy) was hand-condensed on the treated surfaces. After thermocycling, the
      bond strengths were calculated by testing the specimens in shear. Field-emission
      SEM examinations were carried out to evaluate the effects of different treatments
      on the dentin-amalgam interface of MO/OD cavities treated under the same
      protocol. RESULTS: Statistical analysis revealed that Prime & Bond 2.0/Dyract
      Cem, Amalgambond Plus, and Scotchbond Multi-Purpose Plus resulted in the highest
      shear bond strengths. The field-emission SEM observations showed accumulation of
      the fluid adhesive resin underneath the amalgam restoration, and an
      interpenetration between the amalgam and the adhesive resin, except for OptiBond
      and OptiBond FL. All systems, but Fuji Duet, formed an acid-resistant resin
      dentin interdiffusion zone.

PMID- 9580239
TI  - Solubilization of diazepam.
AB  - Several attempts to increase diazepam solubility are in the literature. This
      study discusses these different solubilization approaches. Specific reference is
      given to the rationale in the application of pH control, cosolvency, surfactants,
      and cyclodextrins. It was found than cosolvency is a more attractive means of
      solubilizing diazepam than either pH control, surfactants, or cyclodextrins.
      Advantages, assumptions, and limitations of these diazepam solubilization
      techniques are also described.

PMID- 9580240
TI  - Optimized serum pancreolauryl test for differentiating patients with and without
      chronic pancreatitis.
AB  - The serum pancreolauryl test has limited sensitivity for detecting mild
      pancreatic insufficiency. The aim of this study was to optimize the serum
      pancreolauryl test so as to increase the probability of positive results in
      patients with chronic pancreatitis. The study had three parts. First, the
      sampling time was optimized by analyzing retrospectively the frequency of
      fluorescein peaks at different times from 0 to 240 min in 560 consecutive
      patients. Second, the calculation of serum fluorescein concentrations by means of
      a standard calibration factor was prospectively compared in 271 consecutive
      patients with a modification involving a specimen-specific calibration factor for
      each patient. Third, the clinical utility of the intravenous injection of
      secretin before ingestion of the test meal was prospectively evaluated in a
      further 32 patients. As a result, the optimized serum pancreolauryl test
      developed differs from the former version of the test in utilizing intravenous
      administration of secretin before the test meal, calculation of serum fluorescein
      based on specimen-specific calibration factors, and blood samples taken only at 0
      (basal), 120, 150, 180, and 240 min. This optimized pancreolauryl test was
      abnormal more frequently in patients with chronic pancreatitis than was the
      formerly used test, especially for cases of mild and moderate disease.

PMID- 9580241
TI  - Expression of the leukocyte early activation antigen CD69 is regulated by the
      transcription factor AP-1.
AB  - The leukocyte Ag CD69, one of the earliest cell surface activation Ags, is up
      regulated at the transcriptional level by proinflammatory stimuli involving the
      NF-kappaB/Rel family of transcription factors. However, promoter fragments
      lacking a critical kappaB motif respond to other stimuli such as phorbol esters
      and triggering Abs against TCR/CD3. Since the 5' promoter flanking region of the
      CD69 gene contains several putative binding sequences for transcription factor
      activating protein-1 (AP-1), we explored its role in the inducible expression of
      CD69. Stimuli that induce AP-1, but not NF-kappaB, such as pyrrolidine
      dithiocarbamate, augmented the cell surface expression of CD69 as well as its
      mRNA levels, and the promoter activity of the CD69 gene. This up-regulation is
      accompanied by an increased binding of jun and fos family members to a consensus
      AP-1 binding site of the proximal (-16) CD69 promoter region, which seems to be
      functionally responsive to different activation signals and is trans activated by
      c-jun expression vectors. Furthermore, cotransfection of a dominant negative
      version of c-jun, but not IkappaB, abolished the inducible transcriptional
      activity of the CD69 promoter. In conclusion, the inducible expression of the
      CD69 gene by mitogenic signals is regulated by the transcription factor AP-1.

PMID- 9580242
TI  - Evaluation of a digital radiography to estimate working length.
AB  - The working lengths obtained with different methods in single-rooted teeth were
      compared. An endodontic rule in millimeters and calipers was used as a direct
      method of measurement (on endodontic files). As indirect methods, measurements
      were taken from conventional x-rays with calipers and with a digital radiological
      measurement system. No statistically significant differences were obtained
      between the direct and indirect methods. Three vertical angulations were taken
      for the indirect methods (0 degree, 15 degrees, and 30 degrees). No significant
      differences were found between results for the two indirect methods versus the
      standard method except for the 30 degrees angulation, which resulted in an
      impression of a shortened image of about 1.5 mm when using the indirect methods
      (significance level: alpha = 0.05).

PMID- 9580243
TI  - Predictive factors for rupture of thoracoabdominal aortic aneurysm.
AB  - PURPOSE: To identify the predictive risk factors for rupture of thoracoabdominal
      aortic aneurysms (TAA). METHODS: Thirty-one patients with TAA who did not have
      the indications for surgical repair of the aneurysm were selected. Inclusion
      criteria were maximum diameter less than 60 mm, refusal of surgical treatment,
      and high surgical risk. The selected patients participated in a prospective
      follow-up study for a median period of 47 months and underwent at least two
      thoracoabdominal computed tomographic scans a year to measure transverse and
      anteroposterior diameters. Identification of the predictive factors associated
      with rupture was undertaken with multivariate analysis by means of Cox regression
      model. RESULTS: During the study period five patients underwent elective repair,
      six died of unrelated causes, nine had aneurysms that ruptured (all with
      diameters greater than 50 mm), and 11 reached the end of the study without
      rupture or surgical management. Initial anteroposterior diameter and annual
      growth rate of the anteroposterior diameter were the variables associated with
      rupture of the TAA according to the multivariate statistical analysis by means of
      Cox regression model. CONCLUSION: We recommend elective repair for a fit patient
      with asymptomatic TAA with an initial anteroposterior diameter of 50 mm only when
      there is an annual growth rate of at least 10 mm. Patients with similar diameters
      but with smaller annual growth rates should be treated conservatively and undergo
      thoracoabdominal computed tomography every 6 months. Patients with an initial
      anteroposterior diameter of 60 mm and an annual growth rate of 6 mm should
      undergo surgical treatment. These guidelines for elective repair of TAA are based
      on the results of a relatively small series and have to be carefully
      individualized for each patient.

PMID- 9580244
TI  - Inhibitory activity of a nisin-producing starter culture on Listeria innocua in
      raw ewes milk Manchego cheese.
AB  - The inhibitory activity of nisin-producing Lactococcus lactis subsp. lactis ESI
      515 on the survival of Listeria innocua during ripening of raw ewes milk Manchego
      cheese was investigated. After 60 days of ripening, counts of L. innocua in
      cheese were 4.08 log units lower than the control when Lc. lactis subsp. lactis
      ESI 515 was used as a single-strain starter. Nisin activity was detected in
      cheeses manufactured with Lc. lactis subsp. lactis ESI 515 throughout the
      ripening period.

PMID- 9580245
TI  - Diffuse large B-cell lymphoma: is morphologic subdivision useful in clinical
      management?
AB  - The diffuse large B-cell lymphoma category of the REAL classification encompasses
      different morphologic lymphoma subtypes in a single entity. The aim of this study
      is to determine the influence of the morphologic subdivision within this category
      with respect to clinical features and response to treatment. From January 1993 to
      October 1996, 132 patients were diagnosed de novo with diffuse large B-cell
      lymphoma in our institution. All cases were classified according to the REAL and
      the Updated Kiel classifications, and immunohistochemical study was performed in
      all of them. Sixty-three per cent of patients received chemotherapy with a
      curative approach. Of the 105 assessable patients, 80 cases (74%) were classified
      as centroblastic (CB) and 25 cases (26%) as immunoblastic (IB), according to the
      updated Kiel classification. These 2 subsets of lymphomas did not differ with
      respect to major clinical features and laboratory parameters. Both groups had a
      similar complete response rate with a uniform therapeutic approach and the
      overall 2-yr survival did not show statistical differences (49% in CB vs. 45% in
      IB). In conclusion, for clinicians, morphologic subdivision of the diffuse large
      B-cell lymphoma category into CB and IB subtypes has little clinical and
      prognostic significance.

PMID- 9580246
TI  - Natural killer cell development and function precede alpha beta T cell
      differentiation in mouse fetal thymic ontogeny.
AB  - Natural killer (NK) cells mediate MHC-unrestricted cytolysis of virus-infected
      cells and tumor cells. In the adult mouse, NK cells are bone marrow-derived
      lymphocytes that mature predominantly in extrathymic locations but have also been
      suggested to share a common intrathymic progenitor with T lymphocytes. However,
      mature NK cells are thought to be absent in mouse fetal ontogeny. We report the
      existence of thymocytes with a mature NK cell phenotype (NK1.1+/CD117-) as early
      as day 13 of gestation, approximately 3 days before the appearance of CD4+/CD8+
      cells in T lymphocyte development. These mature fetal thymic NK cells express
      genes associated with NK cell effector function and, when freshly isolated,
      display MHC-unrestricted cytolytic activity in vitro. Moreover, the capacity of
      fetal thymic NK cells for sustained growth both in vitro and in vivo, in addition
      to their close phenotypic resemblance to early precursor thymocytes, confounds
      previous assessments of NK lineage precursor function. Thus, mature NK cells may
      have been inadvertently included in previous attempts to identify multipotent and
      bipotent precursor thymocytes. These results provide the first evidence of
      functional NK lymphocytes in mouse fetal ontogeny and demonstrate that NK cell
      maturation precedes alpha beta T cell development in the fetal thymus.

PMID- 9580247
TI  - Effects of a short-acting insulin analog (Insulin Lispro) versus regular insulin
      on lipid metabolism in insulin-dependent diabetes mellitus.
AB  - Insulin Lispro (IL) is a short-acting insulin analog that better reproduces the
      physiological postprandial insulin profile. The aim of this study was to compare
      the effects of intensive insulin therapy on lipid metabolism using preprandial IL
      and regular insulin (RI) in 10 insulin-dependent diabetes mellitus (IDDM)
      subjects. The mean hemoglobin A1c (HbA1c) at baseline was 7.13% +/- 1.2% and did
      not change after both treatments. In IDDM patients, total cholesterol and
      triglyceride levels appeared lower after RI than after IL. The low-density
      lipoprotein (LDL) to high-density lipoprotein (HDL) ratio significantly decreased
      only after RI (baseline, 2.01 +/- 0.6; IL, 1.88 +/- 0.6; RI, 1.71 +/- 0.5, P <
      .05). Although no very-low-density lipoprotein (VLDL) composition abnormalities
      were observed at baseline, the protein content was lower (P < .05) after IL
      (8.13% +/- 2.93%) than after RI (11.93% +/- 3.41%). Intermediate-density
      lipoprotein (IDL) protein depletion at baseline (6.14% +/- 6.84%) was normalized
      after both treatments (IL, 11.09% +/- 12.14%; RI, 10.38% +/- 16.68%, P < .05).
      LDL, HDL, HDL2, and HDL3 composition abnormalities were similar after both
      treatments and did not normalize. IDDM and control subjects showed similar LDL
      subfraction distribution at baseline and after both treatments. Two-hour
      postprandial VLDL composition alterations, although improved after RI, completely
      normalized after IL (P < .05). Lipoprotein lipase (LPL) and cholesteryl ester
      transfer protein (CETP) activities were similar to the control group and did not
      change after both treatments. Hepatic lipase (HL) activity was lower in diabetic
      patients (39.6 +/- 35.2 v 87.0 +/- 27.1 U/L, P < .01) and remained lower after
      both treatments. In conclusion, in IDDM patients, IL (injected immediately before
      the meal) may offer small different effects on lipoprotein metabolism versus RI
      (injected 30 minutes before the meal) that, taken together, do not seem relevant.

PMID- 9580248
TI  - Hepatitis B virus infection.

PMID- 9580249
TI  - Detailed analysis of a 17q21 microdissection library by sequence bioinformatics
      and isolation of region-specific clones.
AB  - A region-specific microdissection library originating from human chromosome
      17q21, was constructed using the MboI linker-adaptor microcloning technique. DNA
      sequencing of 241 microclones resulted in the identification of 74 novel coding
      sequences, paralogs of known genes, and known, but previously unmapped, genes or
      expressed sequence tags that were "virtually" mapped to chromosome 17q21. By
      pooling the microclones as multiplexed hybridization probes, and by virtue of
      their origin on 17q21, we were able to identify approximately 150 P1 clones from
      the human Reference Library Data Base P1 Library that potentially map to
      chromosome 17q21. Verification of the 17q21 location of 16 P1 clones was
      accomplished by PCR analysis with STS primer pairs to known 17q21 genes or by
      FISH. Our results demonstrate the substantial advantage of combining the sequence
      analysis of microclones with multiplex hybridization strategies for gene
      discovery and mapping specific gene rich regions of the genome.

PMID- 9580250
TI  - Arenavirus phylogeny: a new insight.
AB  - Arenaviridae is a worldwide distributed family, of enveloped, single stranded,
      RNA viruses. The arenaviruses were divided in two major groups (Old World and New
      World), based on serological properties and genetic data, as well as the
      geographic distribution. In this study the phylogenetic relationship among the
      members of the Arenaviridae was examined, using the reported genomic sequences.
      The comparison of the aligned nucleotide sequences of the S RNA and the predicted
      amino acid sequences of the GPC and N proteins, together with the phylogenetic
      analysis, strongly suggest a possible kinship of Pichinde and Oliveros viruses,
      with the Old World arenavirus group. This analysis points at the evolutive
      relationships between the arenaviruses of the Americas and can be used to
      evaluate the different hypotheses about their origin.

PMID- 9580251
TI  - During the initiation of fermentation overexpression of hexokinase PII in yeast
      transiently causes a similar deregulation of glycolysis as deletion of Tps1.
AB  - In the yeast Saccharomyces cerevisiae a novel control exerted by TPS1 (= GGS1 =
      FDP1 = BYP1 = CIF1 = GLC6 = TSS1)-encoded trehalose-6-phosphate synthase, is
      essential for restriction of glucose influx into glycolysis apparently by
      inhibiting hexokinase activity in vivo. We show that up to 50-fold overexpression
      of hexokinase does not noticeably affect growth on glucose or fructose in wild
      type cells. However, it causes higher levels of glucose-6-phosphate, fructose-6
      phosphate and also faster accumulation of fructose-1,6-bisphosphate during the
      initiation of fermentation. The levels of ATP and Pi correlated inversely with
      the higher sugar phosphate levels. In the first minutes after glucose addition,
      the metabolite pattern observed was intermediate between those of the tps1 delta
      mutant and the wild-type strain. Apparently, during the start-up of fermentation
      hexokinase is more rate-limiting in the first section of glycolysis than
      phosphofructokinase. We have developed a method to measure the free intracellular
      glucose level which is based on the simultaneous addition of D-glucose and an
      equal concentration of radiolabelled L-glucose. Since the latter is not
      transported, the free intracellular glucose level can be calculated as the
      difference between the total D-glucose measured (intracellular +
      periplasmic/extracellular) and the total L-glucose measured
      (periplasmic/extracellular). The intracellular glucose level rose in 5 min after
      addition of 100 mM-glucose to 0.5-2 mM in the wild-type strain, +/- 10 mM in a
      hxk1 delta hxk2 delta glk1 delta and 2-3 mM in a tps1 delta strain. In the
      strains overexpressing hexokinase PII the level of free intracellular glucose was
      not reduced. Overexpression of hexokinase PII never produced a strong effect on
      the rate of ethanol production and glucose consumption. Our results show that
      overexpression of hexokinase does not cause the same phenotype as deletion of
      Tps1. However, it mimics it transiently during the initiation of fermentation.
      Afterwards, the Tps1-dependent control system is apparently able to restrict
      properly up to 50-fold higher hexokinase activity.

PMID- 9580252
TI  - Genomic profile of Romanian M. tuberculosis strains appreciated by spoligotyping.

PMID- 9580253
TI  - Current status of guided periodontal tissue regeneration.

PMID- 9580254
TI  - Age-related changes in populations of aortic glycosaminoglycans: species with low
      affinity for plasma low-density lipoproteins, and not species with high affinity,
      are preferentially affected.
AB  - Glycosaminoglycans were extracted from the intima and media layers of normal
      human thoracic aortas from donors of different ages. The arterial segments were
      devoid of macroscopically visible lesions obtained from patients who had no
      clinically evident cardiovascular disease. Total glycosaminoglycan content
      increases during the first 40 years of life. Changes in the content of hyaluronic
      acid and heparan sulfate are less noticeable. The content of chondroitin sulfate
      (mainly the 6-isomer) increases, whereas dermatan sulfate remains constant.
      Plasma LDL-affinity chromatography of dermatan sulfate+chondroitin 4/6-sulfate
      fractions allowed the separation of LDL high- and low-affinity glycosaminoglycan
      species. Remarkably, only glycosaminoglycan species with low affinity for plasma
      LDL increase with age in the disease-free areas of human thoracic aortas studied.
      These results suggest that age-related changes in glycosaminoglycan composition
      of the arterial wall do not contribute to increased deposition of plasma LDL.
      However, the alternative explanation that individuals with arterial
      glycosaminoglycans that avidly bind LDL would develop early and severe
      cardiovascular disease and would thus be excluded from our analysis cannot be
      ruled out.

PMID- 9580256
TI  - Angiocentric cutaneous T-cell lymphoma of childhood (hydroa-like lymphoma): a
      distinctive type of cutaneous T-cell lymphoma.
AB  - BACKGROUND: Angiocentric cutaneous T-cell lymphomas of childhood (ACTCLC) are an
      unusual type of T-cell lymphomas that present with a vesiculopapular eruption
      mimicking hydroa vacciniforme. Most patients have been children from Asia and
      Latin America. OBJECTIVE: The purpose of this study was to describe four cases of
      ACTCLC; to discuss its clinical, histopathologic, and immunohistochemical
      features; to consider its possible relationship to the Epstein-Barr virus (EBV);
      and to clarify its classification within the spectrum of angiocentric lymphomas.
      METHODS: The clinical, histopathologic, and immunohistochemical features of four
      cases of ACTCLC were identified and analyzed. In addition in situ hybridization
      for EBV was performed in all cases. RESULTS: The clinical features were similar
      to previous cases reported under different names, such as hydroa-like lymphomas,
      edematous, scarring vasculitic panniculitis. Histologically, all showed
      angiocentric infiltrates composed mainly of T cells. In all cases there were
      variable numbers of CD30+ cells. The EBV was present in three of the cases.
      CONCLUSION: ACTCLC is a distinct type of T-cell lymphoma. It affects mainly
      children, and the EBV appears to play a role in the pathogenesis of this disease.

PMID- 9580257
TI  - Allergenic cross-reactivity between third stage larvae of Hysterothylacium
      aduncum and Anisakis simplex.

PMID- 9580255
TI  - Interferon-alpha2b therapy is efficacious in Asian-Americans with chronic
      hepatitis B infection: a prospective controlled trial.
AB  - Chronic hepatitis B virus infection is endemic in Asian communities in the United
      States. The purpose of the current study was to compare the antiviral efficacy of
      interferon-alpha2b in a group of adult Asian patients chronically infected with
      hepatitis B with active replication compared to a control group of Caucasian
      patients treated with the same regimen. Patients with entry aminotransferase
      (ALT) levels greater than three times the upper limit of normal received
      interferon-alpha2b, 5 million units, subcutaneously daily for 16 weeks. Patients
      with pretreatment ALT levels 1.5-3 times the upper limit of normal received
      prednisone for a total of six weeks prior to interferon starting at 60 mg daily
      with reduction in dosage by 20 mg every two weeks with a two-week period between
      finishing prednisone and starting interferon-alpha2b. Eight (62%) of the 13
      Asians and six (60%) of the 10 Caucasians cleared HBeAg and HBV DNA from serum
      (NS). By the end of one year of follow-up after therapy, four (67%) of six
      Caucasian responders but none of the Asian responders had cleared hepatitis B
      surface antigen from serum (P < 0.05). Loss of serum markers of active
      replication appeared less durable in the Asian responders compared to the
      Caucasians with reappearance of serum HBeAg in two (25%) of eight of the former
      but only one (17%) of the latter group. Three other Asian patients subsequently
      redeveloped HBeAg in serum. It is concluded that adult Asian-Americans have an
      identical initial response rate to antiviral therapy with interferon-alpha2b;
      however, the response may be less durable and does not usually lead to loss of
      HBsAg.

PMID- 9580258
TI  - Residual stresses in ultra-high molecular weight polyethylene loaded cyclically
      by a rigid moving indenter in nonconforming geometries.
AB  - The characterization of stress and deformation fields that incorporate moving
      cyclic loads and nonlinear material response in ultra-high molecular weight
      polyethylene components for total knee replacements is required to quantify
      mechanisms of surface damage. A simulation of stresses in polyethylene components
      for total knee replacement subjected to cyclic moving loads was performed with
      use of nonlinear finite element analysis. Convergence to a steady-state cycle of
      stress and deformation was observed within five cycles of loading. Differential
      plastic deformation under the surface of the polyethylene led to horizontal
      residual stresses that were tensile at the surface and compressive in the
      subsurface. The magnitudes of the residual stresses indicate their importance in
      surface failure mechanisms. Horizontal residual tensile stresses at the surface
      are consistent with the initiation and propagation of surface cracks that could
      cause pitting in polyethylene. Horizontal residual compressive stresses under the
      surface could cause such cracks to arrest or turn and thus limit damage to a
      region just beneath the surface. The results emphasize the importance of
      incorporating nonlinear effects to simulate long-term stress fields associated
      with surface damage in polyethylene.

PMID- 9580259
TI  - Is there a role for nitric oxide in tumor angiogenesis?

PMID- 9580260
TI  - Altered synaptic physiology and reduced susceptibility to kainate-induced
      seizures in GluR6-deficient mice.
AB  - L-glutamate, the neurotransmitter of the majority of excitatory synapses in the
      brain, acts on three classes of ionotropic receptors: NMDA (N-methyl-D
      aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and
      kainate receptors. Little is known about the physiological role of kainate
      receptors because in many experimental situations it is not possible to
      distinguish them from AMPA receptors. Mice with disrupted kainate receptor genes
      enable the study of the specific role of kainate receptors in synaptic
      transmission as well as in the neurotoxic effects of kainate. We have now
      generated mutant mice lacking the kainate-receptor subunit GluR6. The hippocampal
      neurons in the CA3 region of these mutant mice are much less sensitive to
      kainate. In addition, a postsynaptic kainate current evoked in CA3 neurons by a
      train of stimulation of the mossy fibre system is absent in the mutant. We find
      that GluR6-deficient mice are less susceptible to systemic administration of
      kainate, as judged by onset of seizures and by the activation of immediate early
      genes in the hippocampus. Our results indicate that kainate receptors containing
      the GluR6 subunit are important in synaptic transmission as well as in the
      epileptogenic effects of kainate.

PMID- 9580261
TI  - [Treatment of respiratory insufficiency in the patient with limited airflow].

PMID- 9580262
TI  - [Evolution of the filling pattern of the left ventricle during the first year
      after an acute myocardial infarct. The influence of the infarct size].
AB  - OBJECTIVES: Acute myocardial infarction induces diastolic dysfunction as a result
      of the alteration of left ventricular relaxation and stiffness caused by ischemia
      and fibrosis. This study analyzes the association of infarct size with the
      diastolic filling pattern and the evolution of the latter during the first
      postinfarction year. PATIENTS AND METHODS: The study group consisted of 68
      patients with a first acute myocardial infarction treated with thrombolytic
      agents. A Doppler echocardiography was performed at 8 +/- 2, 32 +/- 7 and 370 +/-
      23 days after infarction. Five measurements of the ratio between E and A waves
      peak velocities (E/A ratio) and of the E deceleration time (EDT, ms) were
      averaged in each echocardiographic study. The patients were divided according to
      infarct size into a large infarct group (creatine kinase > 1,000 U/ml; 1,913 +/-
      883; n = 26) and a small infarct group (creatine kinase < 1,000 U/ml; 556 +/-
      227; n = 42). RESULTS: The large infarct group exhibited a greater E/A ratio and
      shorter EDT than the small infarct group in the first week (E/A ratio: 1.4 +/-
      0.7 vs 0.8 +/- 0.3; p = 0.0001; EDT: 159 +/- 49 vs 192 +/- 56; p = 0.02) and at
      one month (E/A ratio: 1.2 +/- 0.7 vs 0.9 +/- 0.3; p = 0.01; EDT: 170 +/- 55 vs
      207 +/- 40; p = 0.004); however no differences were observed between either group
      at one year in either E/A ratio (0.8 +/- 0.2 vs 0.9 +/- 0.4; NS) or EDT (207 +/-
      44 vs 219 +/- 54; NS). In the large infarct group, E/A ratio decreased and EDT
      increased at one year compared to the first week (E/A ratio: p = 0.0004; EDT: p =
      0.0001) and the first month (E/A: p = 0.02; EDT: p = 0.003); in contrast, in the
      small infarct group there were no significant differences in E/A ratio nor EDT
      during the first year postinfarction. CONCLUSIONS: In the first month
      postinfarction, large infarcts exhibit a greater E/A ratio and shorter EDT than
      small infarcts. The evolution of large infarcts is characterized by an
      attenuation of this pattern, with a progressive reduction of E/A ratio and
      prolongation of EDT during the first year post-infarction.

PMID- 9580263
TI  - [Role of adenosine triphosphate (ATP) in head-up tilt-induced syncope].
AB  - INTRODUCTION AND OBJECTIVES: Recent studies have demonstrated that adenosine is
      an endogenous modulator of the cardiac excitatory afferent nerves, and could
      provoke a vasovagal response during head-up tilt test. Isoproterenol has been the
      drug of choice to increase the sensitivity of this testing. The aim of the
      present study was to analyze the role of adenosine in head-up tilt-induced
      syncope in susceptible patients, and to compare the relative sensitivities of
      adenosine and isoproterenol. METHODS: Thirty patients with unexplained syncope
      (16 female and 14 male, mean age 37.1 +/- 18 years), no heart disease and
      negative baseline head-up tilt test were studied. After the baseline test,
      patients were randomized to receive adenosine triphosphate (bolus injections of
      3, 6 and 9 mg/ 5 min) or isoproterenol (bolus injections of 2, 4 and 6
      micrograms/5 min) and underwent a second tilt test. After 15 min at rest,
      patients received the alternative drug and a third test was performed. Eleven
      normal control subjects were tested with adenosine in the upright position to
      determine its effects. RESULTS: A vasovagal response was induced in 7 patients
      (23.3%) after ATP administration. Nine patients (30%) showed a positive response
      with isoproterenol. Only 2 patients (6.6%) showed a positive response with both
      drugs. Of the control subjects, one (9%) had a vasovagal response after ATP
      administration. CONCLUSIONS: We conclude that adenosine triphosphate seems to be
      a useful tool to provoke vasovagal reaction in susceptible patients during head
      up tilt test.

PMID- 9580264
TI  - [National Commission of Urology].

PMID- 9580265
TI  - [Histomorphometry study of the effect of an inhibitor of 5-alpha reductase on the
      coating of human prostate explants in tissue culture].
AB  - Histomorphometric study of hyperplastic human prostate explants coating grown "in
      vitro" to evaluate the response to a 5-alpha-reductase inhibitor (finasteride).
      Explants were grown for four weeks in three groups, one in growth medium alone
      (RPM1-1640), one supplemented with testosterone and one supplemented with
      testosterone plus finasteride. Explants underwent histological studies,
      quantifying the surface and thickness of the coating epithelium. Study of the
      values obtained from the different samples show significant differences (p <
      0.001) for the coated surface and its thickness between groups supplemented with
      testosterone and testosterone + finasteride, and so it can be inferred that this
      compound (finasteride) would blockade basal cells proliferation and their
      migration on the explant surface.

PMID- 9580266
TI  - [Genital autoaggression. An unusual presentation].
AB  - Self-injuries are relatively common and usually consist in incisive injuries on
      the penis and the scrotum. This paper presents one case of genital self-injury by
      injection of petrol on the back of the penis. A description is offered of the
      clinical form of presentation, as well as the good evolution following medical
      treatment. Finally, a revision of likely complications is included.

PMID- 9580267
TI  - [Follicular cystitis. Presentation as a bladder pseudotumor].
AB  - Presentation of a case report of follicular cystitis in a 48-year old male
      patient who referred gross haematuria and repeat urinary infections.
      Ultrasonographic and endoscopic examinations show the presence of a vesical
      pseudoneoplasm. Definite diagnosis was achieved through histologic study after
      TUR-biopsy.

PMID- 9580268
TI  - [Hydrocele and cholesterol granuloma of the tunica vaginalis simulating a tumor
      in echography].
AB  - OBJECTIVE: A case of cholesterol granuloma of tunica vaginalis, with an equivocal
      ultrasound image but typical histopathological picture, is described. PATIENT AND
      METHOD: A 33-year-old man complained of a painless scrotal mass of 17 years
      duration. The mass was 10 cm in diameter, could not be transilluminated and
      appeared as paratesticular and solid on ultrasound, suggesting a tumor. At
      operation an old hydrocele with cholesterol crystals and cholesterol granuloma of
      tunica vaginalis was found. A partial resection of tunica vaginalis was
      performed, sparing the testis. COMMENT: Cholesterol granuloma is a rare
      inflammatory reaction of tunica vaginalis, that may simulate an intrascrotal
      tumor on physical examination, on ultrasound and at operation.

PMID- 9580270
TI  - Targeting cancer cell death with a bcl-XS adenovirus.
AB  - Transformation is a complex cellular process that requires several genetic
      abnormalities. In many cases, one of these abnormalities is an inhibition of PCD,
      which provides a selective advantage for tumor cells. This has been recently
      shown in an in vivo model, where overexpression of Bcl-XL, is a crucial step in
      the progression from hyperplasia to neoplasia and is accompanied by a significant
      decrease in tumor apoptosis [56]. Frequently, overexpression of a member of the
      Bcl-2 family results in a block in cell death and appears to nullify many built
      in cellular defense mechanisms against cancer. Such a block presents a problem
      because radiation and chemotherapy, standard cancer treatments, ultimately exert
      their effect by induction of apoptosis and would also be made less effective.
      Therefore, to better treat cancer it may be necessary to develop novel methods to
      overcome the effects of the Bcl-2 family. One way to approach this problem is to
      target the cause--the molecular machinery that allows a cancer cell to survive.
      Advances in our understanding of apoptosis has identified the Bcl-2 family as a
      mediator of most apoptosis pathways, including those initiated by oncogenes,
      tumor suppressor genes, growth factor withdrawal, and external damaging signals.
      Therefore, functional inhibition of Bcl-2 family members is lethal to many cancer
      cells. Using gene transfer technology, we can now deliver genes that accomplish
      this goal. Further investigation will reveal whether this translates to improved
      therapy in the future.

PMID- 9580269
TI  - pRB, p107 and p130 as transcriptional regulators: role in cell growth and
      differentiation.
AB  - The mammalian cell cycle engine, which is composed of cyclin/CDK holoenzymes,
      controls the progression throughout the cell cycle by regulating, at least in
      part, the transcription of two types of genes: genes whose protein products are
      required for DNA metabolism and genes whose protein products are involved in cell
      cycle control. Among the targets of cyclin/CDKs, there is a family of negative
      growth regulators collectively known as pocket proteins. This family of pocket
      proteins includes the product of the retinoblastoma tumor suppressor gene, pRB
      and the functionally and structurally related proteins p107 and p130. In this
      review, the mechanisms by which pocket proteins are thought to regulate cell
      growth and differentiation are discussed.

PMID- 9580272
TI  - [Paroxysmal dyskinesias as the initial manifestation of multiple sclerosis].
AB  - We herein report two patients with paroxysmal dyskinesias (PD) as the initial
      manifestation of multiple sclerosis (MS). PD can occur in clinically definite MS
      or rarely be the presenting symptom. They are produced by demyelinating lesions
      at any level in the motor pathway or in the thalamus. MRI disclosed an area of
      demyelination in the posterior limb of the internal capsule contralateral to the
      PD in the patients reported herein. PD associated with MS do not adjust
      completely to the accepted classifications of PD, therefore they should be
      considered a special category of dyskinesias.

PMID- 9580271
TI  - Synchronization and oscillatory dynamics in heterogeneous, mutually inhibited
      neurons.
AB  - We study some mechanisms responsible for synchronous oscillations and loss of
      synchrony at physiologically relevant frequencies (10-200 Hz) in a network of
      heterogeneous inhibitory neurons. We focus on the factors that determine the
      level of synchrony and frequency of the network response, as well as the effects
      of mild heterogeneity on network dynamics. With mild heterogeneity, synchrony is
      never perfect and is relatively fragile. In addition, the effects of inhibition
      are more complex in mildly heterogeneous networks than in homogeneous ones. In
      the former, synchrony is broken in two distinct ways, depending on the ratio of
      the synaptic decay time to the period of repetitive action potentials (tau s/T),
      where T can be determined either from the network or from a single, self
      inhibiting neuron. With tau s/T > 2, corresponding to large applied current,
      small synaptic strength or large synaptic decay time, the effects of inhibition
      are largely tonic and heterogeneous neurons spike relatively independently. With
      tau s/T < 1, synchrony breaks when faster cells begin to suppress their less
      excitable neighbors; cells that fire remain nearly synchronous. We show
      numerically that the behavior of mildly heterogeneous networks can be related to
      the behavior of single, self-inhibiting cells, which can be studied analytically.

PMID- 9580274
TI  - [The situation of tuberculosis in Spain].

PMID- 9580273
TI  - Beta-amyloid(Phe(SO3H)24)25-35 in rat nucleus basalis induces behavioral
      dysfunctions, impairs learning and memory and disrupts cortical cholinergic
      innervation.
AB  - Long-term behavioral effects, changes in learning and memory functions and
      aberrations of cholinergic fibers projecting to the parietal cortex were
      investigated after bilateral injections of beta-amyloid(Phe(SO3H)24)25-35 peptide
      in rat nucleus basalis magnocellularis (nbm). The beta-amyloid peptide used in
      these experiments contained the original beta-amyloid 25-35 sequence which was
      coupled to a phenylalanine-sulphonate group at position 24. This additional
      residue serves as a protective cap on the molecule without influencing its
      neurotoxic properties and results in water-solubility, stability and low rates of
      peptide metabolism. In this paper, home cage, locomotor and open-field
      activities, passive shock-avoidance and 'Morris' water maze learning abilities
      were assessed throughout a 35-day survival period. Subsequently,
      acetylcholinesterase (AChE) histochemistry was used to visualize alterations of
      parietal cortical cholinergic innervation. In response to the neurotoxic action
      of beta-amyloid(Phe(SO3H)24)25-35, a progressive hyperactivity developed in the
      rats in their home cages which were maintained throughout the 5-week post
      injection period. This was accompanied by a significant hypoactivity in the novel
      environment of a locomotor arena. Beta-amyloid(Phe(SO3H)24)25-35-treated animals
      showed greatly impaired cortical memory functions in the step-through passive
      shock-avoidance paradigm, while spatial learning processes remained unaffected.
      Moreover, beta-amyloid(Phe(SO3H)24)25-35 injections in the nucleus basalis
      suppressed explorative behavior in rats and inhibited conditioned stress
      responses 28 days after surgery. Reductions of cortical cholinergic (AChE
      positive) projections provided anatomical substrate for the behavioral changes.
      This indicated extensive, long-lasting neurodegenerative processes as a result of
      beta-amyloid(Phe(SO3H)24)25-35 infusion.

PMID- 9580275
TI  - [Antiochian genealogies in which idiopathic epilepsy presents familial
      conglomeration. Simulations of power for the detection of genetic linkage].
AB  - OBJECTIVE AND METHODS: We have analyzed a set of multigenerational extended
      pedigrees ascertained from affected cases of idiopathic epilepsy in the
      Antioquian Neurologic Institute. All pedigrees show familial aggregation of
      several forms of non myoclonic idiopathic epilepsy. In a recent paper, we have
      demonstrated that generalized idiopathic epilepsy of the awakening type is better
      explained by the existence of a major gene. In this paper, we have explored by
      simulation techniques the usefulness of the bigger pedigrees for linkage
      analysis. By using simlink and taking into account the parameters of the major
      gene, we have estimated that total power of three families is approximately 100
      million times favoring the linkage detection. RESULTS AND CONCLUSIONS: These
      analyses suggest that the major gene accounting by the susceptibility to develop
      generalized idiopathic epilepsy of the awakening type could be localized by
      typifying affected families belonging to the Paisa community from Antioquia,
      Colombia (Acta Neurol Colomb 1997; 13: 69-75).

PMID- 9580276
TI  - [Physiopathology of vertebrobasilar ischemia].
AB  - Although most of the studies concerning physiopathology of ischemia refer to
      cerebral hemispheres, it seems reasonable to consider that cellular and
      biochemical changes due to ischemia are similar in cerebellum and brain stem,
      which receive blood flow from vertebral and basilar arteries. Anyway, it must be
      noted that arterial distribution and anatomical structure of this part of the
      brain are quite distinct, so there might be differences in tissue vulnerability
      according to severity and duration of ischemia. Cellular injury from ischemia
      results, at first, as a consequence of energy failure that leads to loss of ionic
      homeosthasis and membrane potential. This runs a cascade of reactions which is
      responsible of injury progression. Reperfusion may potentiate this reactions if
      it does not occur early enough. Main mediators of these reactions are acidosis,
      citoplasmic calcium overload and excess of free radicals. Development of an
      inflammatory response and injury to microcirculation contribute to perpetuate the
      process.

PMID- 9580277
TI  - [Posterior cerebral artery syndrome].

PMID- 9580278
TI  - Translocated intestinal bacteria cause spontaneous bacterial peritonitis in
      cirrhotic rats: molecular epidemiologic evidence.
AB  - BACKGROUND/AIMS: Intestinal bacterial translocation is common in cirrhotic rats
      with spontaneous bacterial peritonitis, and it is thought to play a major
      pathogenic role. There has so far been no evidence for clonality between bacteria
      isolated from intestine and ascites. This study aimed to use molecular
      epidemiology techniques to show that spontaneous bacterial peritonitis is due to
      translocated intestinal bacteria. METHODS: Samples of ascitic fluid, portal
      blood, mesenteric lymph nodes and ileal contents from healthy (n=10) and ascitic
      cirrhotic rats with (n=12) or without (n=15) spontaneous bacterial peritonitis
      were cultured. In six infected rats, DNA macrorestriction fragments of 30
      bacterial isolates [Escherichia coli (n=13), Enterococcus faecalis (n=12) and
      Proteus mirabilis (n=5)] from ascites (n=8), mesenteric lymph nodes (n=7), portal
      blood (n=6), and ileal flora (n=9) were compared. RESULTS: Bacterial
      translocation was more frequent in animals with (58%) than in those without
      spontaneous bacterial peritonitis (20%, p=0.049) or controls (10%, p=0.026). The
      same bacterial strain was simultaneously isolated in ascites and in mesenteric
      lymph nodes and/or ileum in 7/8 (87%) instances. The identity rate for bacteria
      present in both ascites and mesenteric lymph nodes was 80% (4/5). Likewise,
      identity was demonstrated in 3/4 instances of bacteria found in both ascites and
      portal blood. CONCLUSIONS: These results indicate that spontaneous bacterial
      peritonitis in cirrhotic rats is mainly due to intestinal bacteria translocated
      to mesenteric lymph nodes. Portal blood could be a less frequent route.

PMID- 9580279
TI  - Longitudinal distortion product otoacoustic emission (DPE) latency changes in
      preterm neonates.
AB  - The purpose of this investigation was to determine what types of changes occur in
      the distortion product otoacoustic emission (DPE) latency with increasing
      postconceptual age. These DPE latency changes were then described in relation to
      developmental changes in conductive and cochlear mechanisms in the neonate.
      Longitudinal DPE latency measurements were obtained from a single ear of 18
      preterm neonates. DPEs were evoked at f2s of 3, 4 and 5 kHz. The longitudinal
      data revealed that DPE latency decreased as a function of postconceptual age for
      f2 of 3 and 4 kHz, but did not change significantly at 5 kHz. These findings
      suggest that (1) the conductive and/or cochlear system have not reached maturity
      in the preterm neonate, (2) DPE latency can be used to measure developmental
      changes in the auditory periphery, and (3) maturational changes need to be
      considered if DPE latency is used to identify auditory dysfunction in neonates.

PMID- 9580280
TI  - Lipoprotein(a) levels in children and adolescents with diabetes.
AB  - OBJECTIVE: To determine lipoprotein(a) in children and adolescents with IDDM and
      assess its relation with Lp(a) levels in their first degree relatives. RESEARCH
      DESIGN AND METHODS: In a cross-sectional study we included 141 IDDM patients, (58
      male and 83 female) with mean ages 12.2 +/- 2.8 and 12.6 +/- 3.1 years,
      respectively. Patients with microalbuminuria, hepatopathy, thyroid dysfunction,
      infectious disease, acute decompensation or surgery three months prior to the
      study, were excluded. Clinical history, physical examination, blood chemistry,
      glycosilated hemoglobin, microalbuminuria and lipid profile including total
      cholesterol triglycerides, HDL-C, Apo A-I, Apo B and Lp(a) were determined.
      Parents and non-diabetic siblings were also studied when feasible. RESULTS: Mean
      plasma concentration of total cholesterol, HDL-C and Apo A-I were significantly
      higher in diabetic boys compared to their non-diabetic sibs. Mean Lp(a) plasma
      values and the prevalence of Lp(a) > 30 mg/dL were similar in the IDDM patients,
      their healthy sibs and parents. Hypercholesterolemia and hypertriglyceridemia
      were more frequent among the IDDM patients. No correlation was found between
      HbA1, and Lp(a) concentrations. However, a correlation was observed between Lp(a)
      plasma concentrations of parents and their diabetic and healthy offspring.
      CONCLUSION: Diabetes mellitus does not seem to affect Lp(a) levels. These data
      are consistent with a genetic regulation of Lp(a) plasma levels.

PMID- 9580282
TI  - [The case-control design in medical research].
AB  - The aim of this paper is to present a conceptual and practical framework of the
      case-control design in medical research. To illustrate this method, practical
      examples directed to clinicians and other health professionals interested in
      medical research are presented. The case-control method is very versatile and
      allows for multiple applications. Guidelines for the selection of cases and
      controls, and some considerations on sample size are presented. In the
      statistical analysis we use concrete examples of how to estimate odds ratios,
      confidence intervals, and methods to control for potential confounders, from
      stratified analysis to logistic regression.

PMID- 9580281
TI  - Diagnostic methods of primary tuberculous pleural effusion in a region with high
      prevalence of tuberculosis. A study in Mexican population.
AB  - STUDY OBJECTIVES: 1) To determine the age distribution of the patients with
      pleural tuberculosis in a region with high prevalence of tuberculosis; and 2) to
      evaluate the efficiency of the methods used in its diagnosis. SETTING: The
      National Institute of Respiratory Diseases in Mexico City, a tertiary reference
      center for pulmonary diseases. DESIGN: A retrospective study. PATIENTS: 452
      consecutive inpatients with diagnosis of pleural effusion from January 1991 to
      September 1996 were reviewed: 133 patients had a diagnosis of tuberculous pleural
      effusion of primary origin without parenchymal abnormalities by chest
      roetgenogram. The others were excluded because of reactivated tuberculosis or non
      tuberculous effusion. MEASUREMENTS AND RESULTS: The patients had a mean age of 42
      +/- 17 years (98 male, 35 female). Pleural granulomas in the morphological study
      were found in 87% whereas the baciloscopy and the culture of the fluid were
      positive in only 8% and 19% respectively. The determination of adenosine
      deaminase (ADA) gave a diagnostic yield of 84%. CONCLUSIONS: 1) Primary
      tuberculosis pleural effusion, reported in the English literature, was also
      present in our adults; 2) the pleural biopsy continued to be the most effective
      method in the diagnosis of the pathology; and 3) the determination of ADA in an
      area with high prevalence of the disease was a reliable and unexpensive
      diagnostic method.

PMID- 9580283
TI  - [Total reconstruction of the posterior wall of the external ear canal with
      allogenic rib cartilage. Technique and results].
AB  - Middle-ear reconstruction using a closed surgical technique has the same surgical
      stages as in combined-approach tympanoplasty. The only special feature is the
      reconstruction of the posterior canal wall and scutum, an essential step. This
      reconstruction process is carried out with allogenic costal cartilage affixed to
      two deep bony slots with fibrin glue. In 90% of cases surgery is done in two
      stages.

PMID- 9580284
TI  - [Laryngeal sarcomatoid carcinoma: clinical, histological and immunohistochemical
      study of four cases].
AB  - The purpose of this study was to confirm how the use of immunohistochemical
      techniques can help to differentiate between tumors with a mixed proliferative
      pattern (epithelial and mesenchymal). It is fundamental to differentiating tumors
      of these characteristics in order to determine the prognosis and plan treatment.
      We used different techniques on tissue samples from four cases diagnosed as
      laryngeal sarcomatoid carcinoma. The results demonstrated that all four were
      sarcomatoid carcinomas, which correlated with the patients' favorable clinical
      evolution. The immunohistochemical study was useful for differentiating tumor
      type in the case of a biopsy specimen obtained from a mixed-pattern neoplasm.

PMID- 9580285
TI  - [Response of cartilaginous neoplasms of the larynx to surgery and alternative
      therapies].
AB  - Three primary cartilaginous tumors of the larynx are reported: two
      chondrosarcomas (including an undifferentiated chondrosarcoma with prolonged
      survival) and one chondroma. The need for accurate histological staging, only
      possible after surgery, is emphasized. Surgery is teh preferred initial
      treatment.

PMID- 9580286
TI  - [Complications of total laryngectomy in relation to the previous radiotherapy].
AB  - Different factors, particularly prior radiotherapy, are associated with the
      occurrence of postoperative complications after total laryngectomy. We compared
      the postoperative complications of 50 patients who underwent total laryngectomy
      without prior radiotherapy and those of 50 patients who underwent total
      laryngectomy for tumor recurrence or persistence after radiotherapy. Twenty-four
      percent of the patients without previous irradiation suffered cervical
      complications compared with 26% of the patients with previous irradiation. The
      most frequent cervical complication was pharyngo-cutaneous fistula, which
      occurred in 12% of the non-irradiated patients and in 18% of the irradiated
      patients. There were no significant differences in the frequency of complications
      or in the occurrence of fistulas in relation to prior radiotherapy. In the group
      of irradiated patients, the proportion of major fistulas was greater. The
      occurrence of cervical complications, particularly pharyngo-cutaneous fistulas,
      significantly prolonged the hospital stay.

PMID- 9580287
TI  - [Thyroid cancer. Epidemiological, diagnostic and therapeutic features].
AB  - A retrospective clinical study was made of 189 cases of thyroid cancer seen in
      our service between 1974 and 1994. Epidemiological, clinical, diagnostic, and
      therapeutic variables were analyzed for each histological type of thyroid
      carcinoma. Total thyroidectomy is the treatment of choice at our institution,
      followed by radioiodine treatment for differentiated carcinomas and external
      radiation and chemotherapy for anaplastic carcinomas. The 5-year survival rate
      after surgical treatment was 72% for all histological types of thyroid carcinoma.
      Permanent postoperative complications occurred in 2% of patients.

PMID- 9580288
TI  - [Tuberculosis of the middle ear. A case report].
AB  - A case of tuberculous otitis media in an immunocompetent 11-year-old boy is
      reported. The difficult diagnosis is highlighted. The bibliography was reviewed.

PMID- 9580290
TI  - [Learning in deep hypnosis. The potentiation of mental abilities?].
AB  - INTRODUCTION: Hypnosis is a well known and efficient psychotherapeutic treatment.
      It has been stated as useful in memory improvement, however, there are only a few
      reports of this method in teaching, and its neurophysiological aspects.
      OBJECTIVE: In this paper, the authors were intended to deal with some students'
      academically difficulties in Histology subject, by improving their mental
      capacity by means of hypnosis, and then, to compare their previous bad
      achievements, just in the same subject, with those obtained in a test applied
      after hypnosis intervention. MATERIAL AND METHODS: In order to fulfil the
      proposals, seven high academically risk students were hypnotized to make them
      study under two very deep trance sessions, in which, some suggestions were given,
      such as: highest concentration, intellectual capacities reinforcement, positive
      affection, and also: Synthesis, reviewing, and generalization capacity
      enhancement. The process went into selective deafness, and selective vision as
      special phenomena. RESULTS AND CONCLUSIONS: Students achievements in the final
      test were compared to those previously obtained in the subject using the Signs
      Statistical Test. A significant improvement was demonstrated after hypnosis
      intervention.

PMID- 9580289
TI  - [Clinical characteristics of the peripheral form of epidemic neuropathy in the
      province of Cienfuegos].
AB  - INTRODUCTION: From October 1992 to September 1993 clinical observations of the
      civil population of Cienfuegos revealed the presence of epidemic neuropathy (EN)
      reaching about 2,000 patients. The clinical manifestations were not uniform.
      Although numerous studies have been carried out in our country, none have
      established the characteristics of EN 'the peripheral form'. MATERIAL AND
      METHODS: We studied the first 50 patients assisted by the neurological services
      of the clinical surgical hospital Dr. Gustavo Aldereguia Lima of Cienfuegos
      diagnosed of EN 'peripheral form' according to the procedure established by
      Ministry of Public Health of Cuba. A clinical history was made for each patient
      consisting of: General data, history of toxic, nutritional, malabsorption factors
      and chronic illnesses; symptoms and a neurological examinations. Laboratory test,
      in a group of patients, were done in sera, urine, cerebrospinal fluid (CSF),
      gastric juice and neurophysiological studies that included computerized evoked
      potentials and electroencephalograms registers. RESULTS: Upon analysis of the
      clinical history, nutritional factors was common to all the patients associated
      to toxic and malabsorption. The clinical forms were neuropathy (NP) 48%,
      myeloneuropathy (MNP) 42% and myelopathy (MP) 10%. Retrobulbar optic neuropathy
      was observed in 42% of the patients and auditory neuropathy in 22%. CONCLUSIONS:
      The clinical characteristics of NP, in our cases, indicated that this disease
      fundamentally affects the sensorial neurons and the sensitive peripheral nerves,
      bilaterally, symmetrically, distally and predominantly in lower limbs. The
      pathological process has been associated with a distal axonopathy. However,
      clinic signs of myelopathy can be found up to 40% frequently combined with
      neuropathy or in isolated form, and seems to affect the posterior and lateral
      columns of the spinal cord, mainly at thoraciclumbar level. Neuropathy of central
      nervous system is unknown since no patient has died of EN.

PMID- 9580291
TI  - [Demand for neuropediatric services in a general referral hospital. III.
      Diagnosis].
AB  - INTRODUCTION AND OBJECTIVES: In order to determine the requirements for
      neuropaediatric attention in the Hospital Miguel Servet of Zaragoza, we studied
      the diagnoses of the 2,046 children evaluated during the 5 year period-May 1990
      to May 1995-, when a neuropediatrician was appointed to the hospital (which
      previously did not have such a specialist). RESULTS: The most frequent problems
      were non-epileptic paroxystic disorders, epilepsies and febrile crises. The
      following is a list in descending order, of diseases affecting these children:
      Prenatal encephalopathies, disorders of development and behaviour, head injury
      (TCE), peripheral nervous system and cranial nerve disorders (which were neither
      traumatic nor secondary to space-occupying lesions), headaches, perinatal
      encephalopathies, infections and para-infectious diseases of the nervous system,
      cardiovascular problems, hydrocephalus, metabolic disorders, hypovision and eye
      disorders, neuromuscular disorders, tumours, dyskinesias, medulla problems and
      neurocutaneous syndromes. CONCLUSIONS: The frequency and diversity of the
      neurological pathology seen in childhood and the continual advances in knowledge
      and the related sciences are more than a single professional person can be
      expected to cope with. Experts are required in areas such as
      electroencephalography and epilepsy, neonatal neurology, the neurological aspects
      of intensive care, neuropsychology, neuro-oncology, neurometabolic disorders,
      neurogenetics and neuromuscular disorders. Neuropediatricians are required to
      control illnesses with great personal, family and social impact, such as the
      neurocutaneous syndromes and myelomeningocoele. Neuropaediatric services working
      in close inter-disciplinary collaboration with other specialists are necessary.

PMID- 9580292
TI  - [Demand for neuropediatric services at a general referral hospital. IV.
      Psychomotor development and physical examination].
AB  - INTRODUCTION AND OBJECTIVE: Diagnosis in neuropediatrics requires a detailed
      personal and family history and thorough physical examination. In this paper we
      study the psychomotor development and physical examination of children evaluated
      during a 5 year period, from May 1990 to May 1995 by a neuropediatrician newly
      appointed to the Hospital Miguel Servet in Zaragoza, which previously did not
      have such a specialist. RESULTS: Psychomotor retardation was seen in 19% of the
      children. In 50% of the children evaluated, significant data was obtained from
      the physical examination. The commonest finding, observed in 14% of the children,
      was of anomalous behaviour or an impression of mental deficiency. In decreasing
      order of frequency other data were: Diffuse pyramidal involvement, cranial nerve
      involvement, anomalous phenotype, microcephaly, microsomy, signs of neuromuscular
      involvement, hemiparesia, macrocephaly, skin markings, scoliosis, signs of
      extrapyramidal involvement, signs of cerebellar involvement, macrosomy and
      sensory disorders. CONCLUSIONS: Diagnosis in neuropediatrics is directed or
      established, sometimes exclusively, by an extensive personal and family history
      and adequate interpretation of this, which in the end depends on the skill of the
      clinician.

PMID- 9580293
TI  - [Partial bilateral agenesis of the posterior arch of the atlas].
AB  - INTRODUCTION: Congenital abnormalities of the posterior arch of the atlas (C-1)
      are very uncommon and not widely known. Isolated partial agenesis of the
      posterior arch of the atlas was initially considered a benign variation without
      any clinical or pathological significance. There is, however, increasing evidence
      that neurological symptoms may occur after minor cervical trauma in patients with
      an isolated partial agenesis of the posterior arch of the atlas, specially the
      types 'C' and 'D' malformations described by Currarino et al. CLINICAL CASE: A 63
      year old woman with cervicalgia and 'seasickness', was study with a plain
      cervical spine radiographs and CT with three-dimensional reconstruction, who
      showed a bilateral partial absence of the posterior arch of C-1 with persistent
      posterior tubercle, corresponded to type 'D' in the classification descrites by
      Currarino et al. CONCLUSIONS: The fact of this pathology can unchain an important
      neurological symptoms after minor cervical trauma, oblige to the physician
      (radiologist, neurologist, neurosurgeon, traumatologist, rehabilitation
      specialist) know this pathology, for to include this patients in a group of the
      risk, and indicate to them who should avoid contact sports and other strenuous
      athletic endeavors, and furthermore value the surgical treatment.

PMID- 9580294
TI  - [Progressive or insufflating congenital porencephaly. Report of a case].

PMID- 9580295
TI  - [Development of a new questionnaire in Spanish for diagnosis of migraine].

PMID- 9580296
TI  - [Status epilepticus and multiple sclerosis].

PMID- 9580297
TI  - [Pneumocystis carinii pneumonia in a patient whose primary cerebral tumor was
      treated with steroids].

PMID- 9580298
TI  - [Meningitis and focal encephalopathy due to varicella zoster virus].

PMID- 9580300
TI  - [Electrical status epilepticus during sleep].

PMID- 9580299
TI  - [Nuclear magnetic resonance in subacute combined degeneration of the spinal cord.
      A case report].

PMID- 9580301
TI  - [Exertion-induced left axial deviation and its value as a disease marker of the
      anterior descending coronary artery].

PMID- 9580302
TI  - [Anorexia nervosa in a patient with type-1 diabetes mellitus].
AB  - Female patient, 21 years of age, with diabetes mellitus type I, admitted due to
      progressive weight loss, with a recent history of impaired glycemic control,
      ketosis and amenorrhea for 12 months. Studies were conducted in order to exclude
      an endocrine or malignant disorder. After nutritional, endocrine and psychiatric
      evaluation, the diagnosis of anorexia nervosa, was made. Therapeutic results and
      clinical course after the first year are shown. The case raises important
      problems, especially within diabetic population, puzzling the clues for diagnosis
      and therapy.

PMID- 9580303
TI  - Acid/base properties of beta-blockers and benzodiazepines in sodium dodecyl
      sulfate micelles. A spectrophotometric and potentiometric study.
AB  - The effect of sodium dodecyl sulfate (SDS) micelles on the acid-base properties
      of two family of pharmaceutical drugs (beta-blockers and benzodiazepines) at 25
      degrees C and I = 0.1 M NaCl have been studied. The characterization of the
      several solution equilibria for the system drug/SDS micelle solution was
      performed by potentiometry and spectrophotometry, below and above the critical
      micelle concentration (cmc). Two widely used models have been applied to quantify
      the effect of micelles on the pKa of the drugs, and the results obtained point to
      different interactions of each family of drugs with the micelles.

PMID- 9580304
TI  - Development of artificial organs to treat chronic renal failure in Latin America.

PMID- 9580305
TI  - Statistical analysis of axial deformity during distraction osteogenesis of the
      tibia.
AB  - In this study, we documented the prevalence of coronal axis malalignment in a
      series of 93 tibias (from 54 patients) lengthened with monolateral fixation. The
      average length obtained by distraction osteogenesis was 8.9 cm (range, 3.5-15.6)
      or 38% of the original bone length (range, 11-78%). Fifty (54%) of 93 tibias had
      documented valgus angulation of > or = 10 degrees or had fixator manipulation
      during the lengthening process for undesirable or progressive angulation; no
      cases of varus angulation were noted. Thirteen (14%) segments had later
      corrective osteotomy for unsatisfactory valgus malalignment. Statistical analysis
      revealed two factors to have a significant effect on the rate of malalignment.
      Those cases that had tibial osteotomy below the proximal one third of the
      original tibial length and those cases in which the fixator was placed > 5
      degrees out of parallel had higher rates of angulation or manipulation (p < 0.001
      and p = 0.002). Although the percentage of original bone lengthened was not
      statistically significant (p = 0.083), it did have an important effect on rates
      of axial malalignment. From this study we conclude that relatively high rates of
      malalignment in the tibia during distraction osteogenesis with monolateral
      external fixation are predominately the result of more distal osteotomies and
      nonparallel fixator placement. Attention to these details in general, and
      particularly where long lengthenings are planned, may significantly reduce this
      common complication.

PMID- 9580306
TI  - Primary lingual abscess presenting as acute swelling of the tongue obstructing
      the upper airway: diagnosis with MR.
AB  - We report the sudden development of an inflammatory process thought to be of the
      floor of the mouth with subsequent involvement of the respiratory airway. MR
      imaging showed an enhancing posterior lingual lesion, consistent with an abscess.
      Immediate surgical drainage relieved the symptoms. MR imaging allowed accurate
      diagnosis, which was essential for surgical planning in a condition that was
      otherwise difficult to diagnose.

PMID- 9580307
TI  - Serum ferritin as a component of the insulin resistance syndrome.
AB  - OBJECTIVE: In epidemiological studies, serum ferritin was the second-strongest
      determinant of blood glucose (after BMI) in regression models and the third
      strongest determinant of serum insulin (after BMI and age). Its concentration
      also correlated positively with plasma triglycerides and apolipoprotein B
      concentrations, and negatively with HDL2 cholesterol. We hypothesized that serum
      ferritin could be a marker of insulin resistance. RESEARCH DESIGN AND METHODS:
      Oral glucose tolerance and insulin sensitivity (SI, minimal model method) were
      prospectively evaluated in 36 healthy subjects. The relationship between serum
      ferritin and metabolic control (as measured by HbA1c levels) was also studied in
      76 consecutive NIDDM patients. RESULTS: In healthy subjects, log-transformed
      serum ferritin (LOGFER) correlated with basal serum glucose (r = 0.44, P =
      0.007), but not with BMI, age, systolic or diastolic blood pressure, total
      cholesterol, VLDL cholesterol, HDL cholesterol, total triglycerides, VLDL
      triglycerides, serum insulin, or HbA1c (all P = NS). Identical results were
      obtained when the two lowest quartiles of serum ferritin were evaluated
      separately. However, in the two highest quartiles, LOGFER correlated with BMI
      (0.50, P = 0.02), diastolic blood pressure (r = 0.8, P < 0.0001), serum LDL
      cholesterol (r = 0.57, P = 0.01), VLDL cholesterol (r = 0.48, P = 0.03), total
      cholesterol and HDL2 and HDL3 subtractions of HDL cholesterol (r = -0.68, -0.76, 
      0.55, P = 0.001. < 0.0001, and 0.01, respectively), total triglycerides (r =
      0.60, P = 0.006), HDL2/HDL3 quotient (P = -0.71, P = 0.001), VLDL triglycerides
      (r = 0.65, P = 0.004), and serum uric acid (r = 0.51, P = 0.03), but not with
      systolic blood pressure (r = 0.38, P = 0.15). After adjusting for BMI, only the
      correlations between LOGFER and diastolic blood pressure (r = 0.7, P = 0.002) and
      HDL2/HDL3 quotient (r = -0.63, P = 0.01) remained significant. Strong
      correlations between LOGFER and glucose area under the curve during oral glucose
      tolerance test (Pearson's r = 0.73, P = 0.001) and SI (r = -0.68, P = 0.001),
      which remained significant after controlling for BMI, were observed. LOGFER (beta
      = -0.44, P = 0.01) and BMI (beta = -0.52, P = 0.004) constituted independent
      predictors of insulin sensitivity in a multivariate analysis (R2 = 0.68). In 76
      consecutive NIDDM outpatients, serum glucose (P < 0.00001) and LOGFER (P = 0.03)
      independently predicted the value of HbA1c (R2 = 0.40) in a multiple linear
      regression analysis. CONCLUSIONS: The correlations among serum ferritin and
      diastolic blood pressure, HDL quotient, glucose area under the curve, and SI
      suggest that serum ferritin could be a marker of the insulin resistance syndrome.
      Serum ferritin may also be an independent determinant of poor metabolic control
      in the diabetic patient.

PMID- 9580308
TI  - Posterior cloaca: a unique defect.
AB  - The authors present nine cases of a unique defect in which urethra and vagina are
      fused together forming a urogenital sinus that deviates posteriorly and opens in
      the anterior rectal wall at the anus or immediately anterior to it. The rectum is
      essentially normal or may be minimally anteriorly mislocated. The authors call
      this defect posterior cloaca. The diagnosis requires a suspicious observer and a
      meticulous examination of the female genitalia. A complete urologic evaluation is
      mandatory because 88% of these patients have important associated urologic
      defects. Our patients were operated on via a posterior sagittal transanorectal
      approach, which allowed a full dissection and mobilization of urethra and vagina
      together to be placed in a normal location. Rectal dissection and mobilization
      was avoided to preserve bowel control. Seven patients enjoy bowel and urinary
      control. One patient was lost to follow-up, and one patient with a severely
      dysplastic sacrum suffers from fecal and urinary incontinence.

PMID- 9580309
TI  - Characterization of the cadmium-binding capacity of Chlorella vulgaris.

PMID- 9580310
TI  - Stiff-man syndrome in a child.

PMID- 9580312
TI  - The influence of hyperestrogenism during in vitro fertilization on the
      fibrinolytic mechanism.
AB  - OBJECTIVE: To evaluate levels of various fibrinolytic factor antigens in women
      during ovulation induction using controlled ovarian hyperstimulation. METHODS:
      Plasma tissue-type plasminogen activator (tPA), urokinase-type plasminogen
      activator (uPA), and the plasminogen activator inhibitors (PAI-1 and PAI-2) were
      evaluated and compared with plasma 17 beta-estradiol levels, ranging from 20
      pg/mL to > 5,000 pg/mL during the course of treatment. Sixteen patients
      undergoing IVF were compared prior to (Controls) and following treatment with
      leuprolide acetate down-regulation followed by menopausal gonadotropin-CG
      ovulation induction for 14 days. RESULTS: A significant positive correlation was
      found between tPA and PAI-1 during treatment, while tPA and PAI-1 were negatively
      correlated with estradiol levels. Mean levels of tPA and PAI-1 significantly
      decreased as estradiol levels increased. CONCLUSIONS: As the plasminogen
      activator decreased with increasing estradiol levels, this suggests a potential
      for thrombosis. However, the major plasminogen activator inhibitor (PAI-1) also
      decreased; thus, the net clinical effect in terms of increased potential for
      thrombosis should be minimal. Furthermore, the levels of both tPA and uPA were
      still within normal ranges. The overall data from this study suggest that ovarian
      hyperstimulation with fertility-enhancing drugs does not enhance the potential
      for thrombosis even though there are elevated 17 beta-estradiol levels.

PMID- 9580313
TI  - Double-blind, randomized controlled trial of interleukin-2 treatment of chronic
      hepatitis B.
AB  - Pilot studies have demonstrated that recombinant interleukin 2 (rIL-2) has an
      indirect antiviral activity against hepatitis B virus, but the minimal dose of
      rIL-2 for induction of this effect was not defined. The aim of the study was to
      ascertain the most efficient dose of rIL-2 for induction of the loss of
      detectable serum HBV-DNA or a 50% or greater decrease in its level. Thirty-one
      patients with chronic hepatitis B, hepatitis B e antigen and serum HBV-DNA
      positive were enrolled in this double-blind randomized controlled trial. Patients
      were divided: Group I (n = 8) placebo; Group II (n = 7) treated with 0.9 MU of
      rIL-2 subcutaneously administered daily for 8 weeks; Group III (n = 8) treated
      with 1.8 MU of rIL-2 under the same schedule; Group IV (n = 8) which received 3.6
      MU of rIL-2 under the same conditions. At the end of treatment 25% of the
      patients in the placebo group, and 13% and 25% in rIL-2 groups III and IV,
      respectively, had a decrease in HBV-DNA higher than 50% of the basal value. None
      of the patients lost serum HBV-DNA. Only three patients (one from group II and
      two from group IV) normalized the ALT levels. Overall, during treatment, ALT
      levels decreased in the treated groups. This decrease occurred simultaneously
      with an increase in serum HBV-DNA concentration. Since the response rate in the
      treated groups was similar to that of the placebo group, rIL-2 is not useful as
      monotherapy for the treatment of chronic hepatitis B at the doses and schedules
      used in this study.

PMID- 9580311
TI  - Hypothalamic synaptogenesis and its relationship with the maturation of hormonal
      secretion.
AB  - 1. Information obtained during the last decade has demonstrated that hypothalamic
      neurons release a wide variety of neuroactive substances, such as
      neurotransmitters, mostly monoamines and amino acids, and neuromodulators such as
      the peptides vasopressin (AVP) and oxytocin (OXT) and hypophysial releasing
      hormones. 2. Synapse formation between hypothalamic neurons was followed at
      different times within a given nucleus and among different nuclei during
      development of the mouse hypothalamus. 3. The amounts of various
      neurotransmitters and hormones were determined at various stages of development.
      4. A correlation is presented of the biochemical and ultrastructural features and
      their functional implications during maturation.

PMID- 9580314
TI  - Advances in the immunogenetics of coeliac disease. Clues for understanding the
      pathogenesis and disease heterogeneity.
AB  - Recent studies using the technique of the human genome screening in families with
      multiple siblings suffering from coeliac disease have suggested the presence of
      at least four different chromosomes in the predisposition to suffer from coeliac
      disease. Two loci in chromosome 6 appear to be important in disease
      susceptibility. Other studies based on cytokine gene polymorphisms have found a
      strong association with a particular haplotype in the TNF locus. This haplotype
      carries a gene for a high secretor phenotype of TNFalpha. The finding may be
      important in understanding the heterogeneity of inflammatory response. Evidence
      has been presented in favour of a predominantly Th1 pattern of cytokine
      production by the coeliac disease associated HLA-DQ restricted T cell clones. HLA
      DQ2 and -DQ8 restricted gliadin-specific T cells have been shown to produce IFN
      gamma, which appears to be an indispensable cytokine in the damage to enterocytes
      encountered in the small intestine, since the histological changes can be blocked
      by anti-IFN-gamma antibodies in vitro. TNF-alpha, also produced by several T cell
      clones, may in conjunction with IFN-gamma have a toxic effect or enhance the IFN
      gamma-induced increase of HLA-class II expression on surface enterocytes. In the
      lamina propria this leads to an increased expression of adhesion molecules such
      as ICAM-1 on T lymphocytes and macrophages. Th1 cells also activate cytotoxic
      CD8+ T cells that migrate in the epithelial layer, and stimulate further LPL
      macrophages to produce IFN-gamma and TNF-alpha enhancing the inflammatory
      response. During this process autoreactive T cells proliferate, creating a
      situation which is very similar to the process that takes place in autoimmune
      diseases. Occasionally, this inflammatory destruction of the small intestinal
      integrity initiated by gluten peptides goes further and develops into a proper
      autoimmune disease which requires the use of immunosuppressive drugs in addition
      to a gluten-free diet.

PMID- 9580315
TI  - The pharmacology of leishmaniasis.
AB  - The development of new strategies on chemotherapy of parasitic protozoan diseases
      is one of the most exciting research fields of recent years. World Health
      Organization (WHO) reports have recognized that the physiology and biochemistry
      of protozoan parasites and the host-parasite relation are the main targets for
      the design of new drugs that can be used in the future against these diseases.

PMID- 9580317
TI  - [Risk of transmission of cholera by fish products: regional perspective in South
      America].
AB  - Cholera returned to South America in January 1991, after almost a century of
      absence. The hygienic status of the countries affected, aggravated by economic
      and political difficulties, allowed the disease to spread rapidly. In Peru,
      fishery products were incriminated from the outset, although without conclusive
      evidence. However, epidemiological and laboratory findings in other countries
      have confirmed the transmission of the disease by these products. The authors
      discuss the effects of the recent cholera epidemic on the trade and consumption
      of fishery products in countries of South America. The actual risk of cholera
      transmission by food and in particular by the consumption of fishery products is
      discussed, and a basis for conducting an accurate evaluation of these risks is
      proposed. Finally, the authors summarise the measures recommended to prevent the
      transmission of cholera by fishery products.

PMID- 9580316
TI  - Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic
      interneurons.
AB  - Neurocalcin (NC) is a recently described calcium-binding protein isolated and
      characterized from bovine brain. NC belongs to the neural calcium-sensor proteins
      defined by the photoreceptor cell-specific protein recoverin that have been
      proposed to be involved in the regulation of calcium-dependent phosphorylation in
      signal transduction pathways. We analyzed the distribution and morphology of the
      NC-immunoreactive (IR) neurons in the rat dorsal hippocampus and the coexistence
      of NC with GABA and different neurochemical markers which label perisomatic
      inhibitory cells [parvalbumin (PV) and cholecystokinin (CCK)], mid-proximal
      dendritic inhibitory cells [calbindin D28k (CB)], distal dendritic inhibitory
      cells [somatostatin (SOM) and neuropeptide Y (NPY)], and interneurons specialized
      to innervate other interneurons [calretinin (CR) and vasoactive intestinal
      polypeptide (VIP)]. NC-IR cells were present in all layers of the dentate gyrus
      and hippocampal fields. In the dentate gyrus, NC-IR cells were concentrated in
      the granule cell layer, especially in the hilar border, whereas in the CA fields
      they were most frequently found in the stratum radiatum. NC-IR cells were
      morphologically heterogeneous and exhibited distinctive features of non-principal
      cells. In the dentate gyrus, pyramidal-like, multipolar and fusiform (horizontal
      and vertical) cells were found. In the CA3 region most NC-IR cells were
      multipolar, but vertical and horizontal fusiform cells also appeared. In the CA1
      region, where NC-IR cells showed most frequently vertically arranged dendrites,
      multipolar, bitufted and fusiform (vertical and horizontal) cells could be
      distinguished. All the NC-IR cells were found to be GABA-IR in all hippocampal
      layers and regions, and they represented about 19% of the GABA-positive cells.
      NC/CB, NC/CR and NC/VIP double-labeled cells were found in all hippocampal
      regions, and represented 29%, 24% and 18% of the NC-IR cells, respectively. NC
      and CCK did not coexist in the dentate gyrus; however, 9% of the NC-IR cells in
      the CA fields also contained CCK. No coexistence of NC with PV, SOM or NPY was
      found in any hippocampal region. We conclude that NC is exclusively expressed by
      interneurons in the rat hippocampus. NC-IR cells are a morphologically and
      neurochemically heterogeneous subset of GABAergic non-principal cells, which, on
      the basis of the known termination pattern of the colocalizing markers, are also
      functionally heterogeneous and are mainly involved in feed-forward dendritic
      inhibition in the commissural-associational and Schaffer collateral termination
      zones (CB containing cells), in innervation of other interneurons (CR- and VIP
      containing cells), and in perisomatic inhibition (CCK-containing cells). NC is
      never present in perisomatic inhibitory PV-containing cells, or in feed-back
      distal dendritic inhibitory SOM/NPY-containing cells.

PMID- 9580318
TI  - The course of relapse across 36 months for smokers from a smoking-cessation
      program.
AB  - The aim of this study is to examine relapse of 72 smokers who stopped smoking
      with a behavioral smoking cessation program and relapse in the period from the
      end-of-treatment to the 36-mo. follow-up. The relapse occurred fundamentally
      between the end-of-treatment and the 6- (53.7% relapse) and the 12-mo. follow-up
      (61.1% relapse), and more slowly beyond 12-mo. follow-ups with 72.2% and 70.4%
      relapse at the 24- and 36-mo. follow-up.

PMID- 9580319
TI  - Preliminary investigation of associations of illness schemata and treatment
      induced reduction in headaches.
AB  - This study examined how illness schemata-ways people organize information about
      illness-change over the course of cognitive-behavioral treatment of chronic
      headache and the extent to which such changes predict reduction of headache. 73
      subjects with chronic migraine, mixed migraine and tension, or tension headache
      were classified on the basis of outcome from imagery-based treatment as Treatment
      responders (n = 24). Treatment nonresponders (n = 27), and Monitoring Controls (n
      = 22). Self-reported illness schemata related to the seriousness and
      changeability of headache were assessed at pretreatment and 8-wk. follow-up.
      While groups did not differ on pretreatment measures of illness schemata, at
      follow-up the Treatment responder group reported higher Changeability scores than
      Treatment-nonresponders and Control subjects and lower Seriousness scores than
      Control subjects. Headache reduction at follow-up was related to follow-up
      Changeability scores, in-session changes in systolic blood pressure and reported
      posttreatment expectations of headache activity, but not pretreatment measures of
      illness schemata. Findings indicate that improvements in headache activity are
      not influenced by the severity of headaches and may change prior to cognitive
      behavioral treatment. Rather, among individuals who show decreases in headache
      activity, changes in beliefs about illness and headache reduction may have
      reciprocal relations both of which result from cognitive behavioral treatment.

PMID- 9580320
TI  - [Using Karnofsky's scale to measure the quality of life].
AB  - Karnofsky's scale is one of the indexes most frequently used to measure cancer
      patients' quality of life. The main problem encountered when trying to verify it
      is the degree of subjectivity inherent in it. Due to this, an attempt was made to
      create a more objective measuring instrument based on Karnofsky's scale. To this
      end, a retrospective study involving 300 outpatients was carried out. For these
      patients, their Karnofsky index was determined by two independent agents: the
      patient's oncologist and the nursing team which complied its measure based on a
      survey answered by the patient himself/herself. The differences between these two
      methods proved to be statistically insignificant.

PMID- 9580321
TI  - [Structuring of the free time of hospitalized patients].

PMID- 9580322
TI  - [Living with a brother's illness].
AB  - The objective of this study is trying to reveal the reactions of healthy children
      facing their brothers oncologic illness through their mothers perception. To
      collecting the data surveying descriptive study with qualitative characteristics
      was realized. An interview with 8 mothers and the informations about their 13
      children analysis allow us to know the reaction of these children facing their
      brothers diagnostic, hospitalization and parents different conducts.

PMID- 9580323
TI  - [The surgical nurse: his/her leadership of auxiliary nursing personnel].
AB  - This investigation as carried out in order to promote follow-up in the studies
      concerning nurse's leadership in the hospital context. Emphasys is given to the
      nurses that works in surgical ward unities. As a theoretical framework, authors
      utilized the model of leadership proposed by Hersey and Blanchard, named
      Situational Leadership. The objective was to analyze the correspondence of
      opinion between nurses and nursing auxiliary personnel about the leadership style
      of nurse should adopt in accordance with the maturity level of an element of the
      auxiliary personnel based on six categories of activities that were studied.
      Authors found out that nurses should adopt the styles of participant leadership,
      such as E3 (participating) and/or E4 (delegating).

PMID- 9580324
TI  - [The opinion of nurses concerning the shift transfer].
AB  - The study intends to survey nurse's opinions regarding shift changes in their
      workplaces. It aims deepening our knowledge about how this activity contributes
      to the work organization, considering the process of caring in nursing. We
      emphasize the importance of shift change and of data gathered by nursing staff as
      a connecting link of the health system. They are fundamental activities for the
      unit work organization, being a decisive factor to maintain the quality of the
      assistance, since they allow updating information about the patient and nursing
      actions adjustment.

PMID- 9580326
TI  - Stability of antigen and agarose used in a double immunodiffusion serologic test
      for Brucella ovis.

PMID- 9580325
TI  - A pharmacokinetic study of peritoneal absorption of glucose and alanine in rats:
      nutritional implications.
AB  - BACKGROUND: The aim of this work was to study the serum bioavailability of
      glucose and alanine after bolus injection into the peritoneal cavity in Wistar
      rats and to determine the influence of their metabolism on the rate of absorption
      of these nutrients. METHODS: A group of animals (n = 14) was infused
      intraperitioneally (i.p.) or i.v. with 2 microCi of nonmetabolizable L-[1-14C]
      glucose diluted in 5 mL of 5% D-glucose/250 g body wt, after which plasma
      radioactivity was determined. A second group of animals (n = 14) received, either
      i.p. or i.v., 3 microCi of nonmetabolizable D-[U-14C] alanine diluted in 2 mL of
      an iso-os-molar L-amino acid solution/250 g body wt, after which both plasma
      radioactivity and L-alanine concentration were determined. The constants of
      absorption from peritoneal cavity (Ka) and elimination from plasma (Ke) and the
      serum absolute bioavailability (BA(a)) after 8 h were calculated assuming a
      bicompartment pharmacokinetic model. RESULTS: L-glucose: Ka = 3.05 +/- 0.97 h-1;
      Ke = 0.40 +/- 0.12 h-1; BA(a) = 94% +/- 4%. D-alanine: Ka = 1.08 +/- 0.40 h-1; Ke
      = 0.11 +/- 0.06 h-1; BAa = 90% +/- 11%. L-alanine: Ka = 1.75 +/- 0.273 h-1; Ke =
      0.02 +/- 0.01 h-1; BA(a) = 99% +/- 1%. No hyperglycemia, hypoglycemia, or
      glycosuria appeared in any case. CONCLUSIONS: The absorption rate from peritoneal
      cavity is nearly 10-fold higher than the elimination rate from plasma for the
      three substrates. Eight hours after i.p. injection an absolute bioavailability
      almost as high as after i.v. injection (i.e., close to 100%) was achieved. The
      metabolism of the nutrients seems to help the peritoneal absorption, as L-alanine
      is better absorbed then D-alanine. These results show that upon i.p. injection
      the studied nutrients are almost completely absorbed in a short period of time
      without hyperglycemia or neoglucogenesis and so suggest that their administration
      may be a feasible approach to feeding patients receiving peritoneal dialysis.
      This model could be applied to other compounds, such as peptides and
      disaccharides.

PMID- 9580327
TI  - Abnormal expression of type 1 plasminogen activator inhibitor and tissue factor
      in severe preeclampsia.
AB  - Preeclampsia is a multisystemic obstetric disease of unknown etiology that is
      commonly associated with fibrin deposition, occlusive lesions in placental
      vasculature, and intrauterine fetal growth retardation. We previously reported
      that type 1 plasminogen activator inhibitor (PAI-1) levels are significantly
      increased in plasma and placenta from pregnant women with preeclampsia compared
      to normal pregnant women. In the present report we localize the expression of
      placental PAI-1 in greater detail and compare it with that of tissue factor (TF),
      a procoagulant molecule, and vitronectin (Vn), a PAI-1 cofactor. We also examine
      the expression of two cytokines, tumor necrosis factor alpha (TNFalpha) and
      interleukin-1 (IL-1), in order to begin to define the underlying mechanisms
      responsible for the elevated levels of PAI-1 and fibrin deposits observed in
      placenta from preeclampsia. We demonstrate a significant increase in PAI-1, TF
      and TNFalpha antigen and PAI-1 and TF mRNA in placentas from preeclamptic
      patients. PAI-1 mRNA was increased not only in syncytiotrophoblast and infarction
      areas, but also in fibroblasts and in some endothelial cells of fetal vessels in
      placentas from preeclamptic patients. However, there was no colocalization
      between PAI-1, TF, Vn and TNFalpha in placental villi. The elevated TNFalpha in
      the placenta may induce PAI-1 and TF, and thus promote the thrombotic alterations
      associated with preeclampsia.

PMID- 9580329
TI  - Healing patterns in recession defects treated with ePTFE membranes and with free
      connective tissue grafts. A histologic and histometric study in the beagle dog.
AB  - This study focussed on the biologic success of 2 different procedures for root
      coverage. In the maxillary canines of 7 beagle dogs, buccal recessions were
      created and treated on one side with an ePTFE membrane (GTR-group) and on the
      contralateral side with a free connective tissue graft from the palate (CT
      group). 2 areas served as negative controls. After 4 months of healing,
      histologic sections were processed and histologically analyzed. The evaluated
      parameters were coverage height, bone, cementum and connective tissue attachment
      regeneration, length of the epithelium, resorption, and ankylosis.
      Histologically, both GTR-group and CT-group produced more new bone, new cementum
      and new connective tissue attachment than the two control teeth. When
      histologically evaluated, the amount of new bone was more pronounced in the GTR
      group than in the CT-group, however, no statistical differences in any of the
      evaluated parameters could be detected between the 2 procedures tested. Frequency
      and distribution of resorption and ankylosis were similar in the GTR-group and in
      the CT-group. Within the limits of this study, no differences in terms of the
      biologic rehabilitation between those recessions treated with ePTFE membranes and
      those treated with a free connective tissue graft could be found.

PMID- 9580328
TI  - Induction of apoptosis by vanilloid compounds does not require de novo gene
      transcription and activator protein 1 activity.
AB  - The vanilloid compounds, capsaicin and resiniferatoxin, are quinone analogues
      that inhibit the NADH-plasma membrane electron transport system and induce
      apoptosis in transformed cells. Because disruption of the mitochondrial
      transmembrane potential (deltapsi(m)) is a common metabolic alteration in all
      apoptotic processes, we have evaluated the role of mitochondrial permeability
      transition in apoptosis induced by vanilloids in Jurkat cells. Using a
      cytofluorimetric approach, we have determined that DNA nuclear loss induced by
      vanilloids is preceded by an increase of the production of reactive oxygen
      species (ROS) and by a subsequent deltapsi(m) dissipation in T-cell lines.
      Overexpression of Bcl-2 and pretreatment with either the immunosuppressant
      cyclosporin A or the glutathione precursor N-acetyl-L-cysteine blocked
      deltapsi(m) disruption and apoptosis, but not the generation of ROS induced by
      these compounds. Capsaicin and resiniferatoxin were found to activate both
      isoforms of c-jun-NH2-kinase (JNK), with a maximal activity after 30 min of
      treatment. Despite the activation of JNK, there was no induction of activator
      protein 1 (AP-1) activity as determined by gel shift assay or of induction of an
      AP-1-responsive reporter. On the other hand, vanilloids did not signal for c-Raf
      kinase and extracellular signal-regulated kinases 1 and 2. We suggest that ROS
      generation by inhibition of the NADH-dependent plasma membrane electron transport
      system resulted in the oxidation of mitochondrial megachannel pores that allows
      for the disruption of deltapsi(m) and apoptosis, and that AP-1 activation is not
      required for vanilloid-induced apoptosis.

PMID- 9580330
TI  - Developmental expression of the tenascin-C is altered by hypothyroidism in the
      rat brain.
AB  - Tenascin-C is an extracellular matrix glycoprotein involved in cell adhesion and
      migration, and neurite outgrowth. Since these processes have been found to be
      under thyroid control in the developing rat brain, we have investigated the
      effect of congenital hypothyroidism on tenascin-C expression. At birth, in situ
      hybridization studies in hypothyroid rats show an abnormal up-regulation of
      tenascin-C in some areas (caudate-putamen, geniculate nuclei, ependymal
      epithelium of the lateral ventricles, hippocampus) and down-regulation in others
      (occipital and retrosplenial cortex, subiculum). With subsequent development,
      hypothyroid animals show higher tenascin-C expression also in the upper layers of
      the cerebral cortex and subplate, and the Bergmann glia of the cerebellum.
      Significantly, thyroxine treatment of hypothyroid rats led to normalization of
      tenascin-C levels in most areas. In agreement with the messenger RNA data,
      hypothyroid rats contain an uniformly higher level of immunoreactive tenascin-C
      protein throughout the brain, particularly in the cerebellum. Suggesting a direct
      cellular effect, thyroid hormone also decreases tenascin-C expression in two
      glial cell lines (C6, B3.1) expressing thyroid receptors. Our results show that
      congenital hypothyroidism causes specific alterations in the pattern of tenascin
      C expression in the rat brain which may at least partially be responsible for
      some of the developmental disturbances observed in this syndrome.

PMID- 9580331
TI  - Effects of hyoscine-N-butylbromide given before romifidine in horses.

PMID- 9580332
TI  - Microvenular haemangioma: a new case in a child.

PMID- 9580333
TI  - [Clinical profile, coronary angiography findings and early outcome in young
      patients with acute myocardial infarction in the thrombolytic era].
AB  - PURPOSE: To assess the clinical, angiographic and early follow-up findings of
      young patients suffering an acute myocardial infarction, in comparison with older
      patients with infarction, in the thrombolytic era. METHODS: A retrospective
      analysis of the medical records of 46 patients < 40 years-old (group I) at the
      time of an acute myocardial infarction was compared with that of 46 older
      patients, randomly selected, presenting with this syndrome between february, 1991
      and february, 1996 (group II). In both groups a comparison was conducted
      regarding the proportions of gender, risk factors, type of infarction (Q vs non
      Q), left ventricular function, coronary anatomy and early mortality (1 month).
      The medical treatment was comparable for both groups, including the utilization
      of thrombolytics. RESULTS: The groups were discriminated only by: higher
      prevalence of smoking, of angiographically normal coronary arteries, and of non
      critical (< 75% reduction of luminal diameter) coronary stenosis in group I; in
      the older group a higher proportion of patients had multivessel disease. Although
      not reaching statistical significance, a trend was observed to a more benign
      early course of the infarction in the patients less than < 40 years-old.
      CONCLUSION: The present findings are similar to those described in the pre
      thrombolytic era, for young patients suffering an acute myocardial infarction.

PMID- 9580334
TI  - [The use of left and right internal thoracic artery grafts for revascularization
      of the left coronary artery].
AB  - PURPOSE: To analyze the late results of patients who underwent left coronary
      myocardial revascularization with both internal thoracic arteries, with the right
      internal thoracic through the transverse sinus. METHODS: From July/83 to
      September/96, 233 patients underwent myocardial revascularization, with ages
      ranging from 35 to 76 (average of 52.8) years. One hundred and eighty five were
      male and 48 female. Internal thoracic arteries (466), saphenous veins (192) and
      epigastric arteries (11) were employed. RESULTS: The hospital mortality was 3%
      and the late mortality was 6.1%. The immediate postoperative bleeding was 0.8%,
      mediastinitis 1.7% and myocardial infarction 2.1%. The immediate and late
      coronariography showed the rates of patency, respectively: left internal thoracic
      artery 98% and 96%, right internal thoracic artery 96% and 92, and saphenous vein
      grafts 80% and 67.5%. CONCLUSION: The main advantage in using both internal
      thoracic arteries in the revascularization of the left coronary branches was the
      better quality of life, the low rates of cardiac events and the absence of
      reoperation due to occlusion of the grafts.

PMID- 9580336
TI  - [Symposium: The admission process in Medical Schools: selection criteria for
      admission to higher education].

PMID- 9580337
TI  - [Predictive value of cognitive variables].

PMID- 9580335
TI  - [Epidemiological transition in Latin America: a comparison of four countries].
AB  - BACKGROUND: In the last decade, Latin America has experienced important
      transformations in its health conditions, due to demographic changes and a rapid
      urbanization process. AIM: To analyze socioeconomic, demographic and
      epidemiological changes in Chile, Guatemala, Mexico and Uruguay and relate them
      to the different stages in the demographic and epidemiological transition of
      these countries. MATERIAL AND METHODS: Data was obtained from official
      information of local and international organizations such as Pan-American Health
      Organization, United Nations, Latin American Center for Demography (CELADE) and
      World Bank. RESULTS: Guatemala is in a pre-transition stage with a high
      proportion of communicable diseases as causes of death (61%) as compared with
      Mexico (22%), Chile (13%) and Uruguay (7%). Mexico is in a prolonged transition
      situation and Chile is close to Uruguay in a post-transitional stage. Despite
      decreasing rates of mortality, the proportion of deaths represented by chronic
      diseases and injuries has increased to over 30% in all countries, except Uruguay.
      Adjusted mortality rates for cardiovascular diseases are lower in Latin American
      countries, as compared to Canada. However, excepting Guatemala, there are
      differences in the pattern of cardiovascular disease, with a higher mortality due
      to cerebrovascular and a lower mortality due to coronary artery diseases.
      CONCLUSIONS: An increment in non communicable diseases is expected for the next
      decades in Latin America. Analysis of demographic and epidemiological transition
      is crucial to define health policies and to adequate health systems to the new
      situations.

PMID- 9580338
TI  - [Analysis of agreement between self-reported and observed information on pubertal
      development among school girls].
AB  - AIM: To test the reliability of the self-classification concerning levels of
      breast and public hair development among female adolescents of different
      socioeconomic groups. MATERIAL AND METHOD: A total of 445 female adolescents
      attending three secondary schools located in Ribeirao Preto, State of S. Paulo,
      Brazil, were studied. After being familiarised with Tanner's tables of breast and
      public hair development, the adolescents were asked to self classify themselves
      according to these variables. The results were compared to those obtained by a
      physical examination carried out soon after. RESULTS: Agreement rates between
      referred and observed information on breast development varied from 57.3% to
      65.2%. For public hair the values varied from 65.4% to 73.5%. Total agreement
      rates for breast and public hair development, when considered simultaneously,
      reached values below 50.0% in the three schools. However, high agreement rates
      were observed for some critical degrees, such as B2, B4 and PH4. CONCLUSIONS:
      Significant events, such as the beginning of pubertal development, the menarche
      and the showing down of the body's development growth could be determined with
      acceptable levels of agreement. The low agreement rates observed for the
      simultaneous analysis of the degree of both breast and public hair show the need
      for the perfecting of methodologies that can replace the physical examination of
      adolescents, once reliable information about pubertal development is obtained in
      field studies.

PMID- 9580339
TI  - Comparative analysis of the vascular actions of diterpenes isolated from
      Euphorbia canariensis.
AB  - We have analysed the effects of 2,3-diepiingol 7,12-diacetate-8-isobutyrate
      (compound 1), ingenol-3-angelate-17-benzoate (compound 2), ingenol-3-angelate-17
      benzoate-20-acetate (compound 3) and 3,5,7,8,9,15-hexahydroxyjatropha-6(17),11
      dien-14-one-5,8-bi s(2-methylbutyrate)-7-(2-methylpropionate) (compound 4), four
      diterpenes isolated from E. canariensis, on the isometric tension developed by
      isolated rabbit basilar and carotid arteries. Concentration-response curves to
      these compounds were obtained cumulatively in both arteries at resting tension
      and active tone (KCl, 50 mM). At resting tension a concentration-dependent
      contraction was induced by the four compounds. In the basilar artery the order of
      potency was 3=1>2=4, without significant differences between Emax values. In the
      carotid artery the order of potency was 3>2=1=4 and there were no significant
      differences between the Emax (maximum effect) values of compounds 1-3, all of
      which were higher than that of compound 4. In pre-contracted basilar artery
      compounds 1-3 induced concentration-dependent relaxation and compound 4 was
      almost ineffective; the order of potency was 3>2=1 without significant
      differences between Emax values. In the carotid artery with active tone the four
      compounds tested induced further contractions; the order of potency was 3>2=4>1
      without significant differences between Emax values. These results show that the
      four diterpenes are potent active substances in rabbit basilar and carotid
      arteries and that there are regional differences between their action. The four
      compounds tested contract basilar and carotid arteries at resting tension.
      Compounds 1-3 relax pre-contracted basilar artery but not carotid artery.

PMID- 9580340
TI  - Electrochemical study of nisoldipine: analytical application in pharmaceutical
      forms and photodegradation.
AB  - The anodic and cathodic behavior of nisoldipine, 3-isobutyl-5-methyl-1,4-dihydro
      2,6-dimethyl-4-(2-nitrophenyl)pyridine-3 ,5-dicarboxylate, are reported. This
      drug belongs to the nitroaryl-1,4-dihydropyridine family, known as calcium
      channel antagonist and employed in therapeuticalls as peripheral and cerebral
      vasodilators, in the treatment of the arterial hypertension. The cathodic
      response corresponds to the reduction of the nitroaromatic group to generate the
      hydroxylamine derivative. The study by dc and d.p.p. reveals the appearance of
      four signals depending on pH: Signal I (pH 1-11.5) R - NO2 + 4H+ + 4e- --> R -
      NHOH + H2O; Signal II (pH 1-5) R - N+H2OH + 2H+ + 2e- --> RN+H3 + H2O; Signal III
      (pH > 11.5) R - NO2 + e- <--> R - NO2.-; Signal IV (pH > 11.5) R - NO2.- + 3e- +
      4H+ --> R - NHOH. In contrast, the anodic response corresponds to the oxidation
      of the 1,4-dihydropyridine ring to generate the corresponding pyridine
      derivative. Both, cathodic (d.p.p.) and anodic signals (d.p.v.) were employed to
      develop analytical methodology for the determination of the drug. The
      repeatability of the measurements for both methods was adequate with R.S.D. of
      1.4% (n = 10) and 2.1% (n = 10) for d.p.p. and d.p.v., respectively. Also
      recovery studies, 103.8% (R.S.D. 2.65%) by d.p.p. and 98.7% (R.S.D. 2.1%) by
      d.p.v. show that the accuracy and precision of the developed methods were
      adequate. The analytical methods were successfully applied to the determination
      of nisoldipine in both tablets and capsules. In addition, a preliminary study of
      the photostability of nisoldipine (using both UV and artificial day light) was
      completed. The identity of the main electroactive photodegradation products by GC
      with spectrometry detection is provided.

PMID- 9580341
TI  - Tonic and bursting activity in the cuneate nucleus of the chloralose-anesthetized
      cat.
AB  - Whole-cell recordings were obtained from cuneate neurons in anesthetized,
      paralysed cats. Stimulation of the contralateral medial lemniscus permitted us to
      separate projection cells from presumed interneurons. Pericruciate motor cortex
      electrical stimulation inhibited postsynaptically all the projection cells (n=57)
      and excited all the presumed interneurons (n=29). The cuneothalamic cells showed
      an oscillatory and a tonic mode of activity. Membrane depolarization and primary
      afferent stimulation converted the oscillatory to the tonic mode. Hyperpolarizing
      current steps applied to projection neurons induced a depolarizing sag and bursts
      of conventional spikes in current-clamp records. This indicates the probable
      existence of low-threshold and hyperpolarization-activated inward currents. Also,
      the hyperpolarization induced on projection cells by motor cortex stimulation
      deinactivated a low-threshold conductance that led to bursting activity. The
      presumed cuneate interneurons had larger and more proximally located peripheral
      receptive fields than the cuneothalamic cells. Finally, experiments specifically
      designed to test whether motor cortex-induced presynaptic inhibition could be
      postsynaptically detected gave negative results. These results demonstrate, for
      the first time, that the cuneothalamic cells possess both bursting and tonic
      firing modes, and that membrane depolarization, whether produced by injection of
      positive current or by primary afferent stimulation, converts the oscillatory
      into the tonic mode.

PMID- 9580342
TI  - Measurement of damage in 210 Mexican patients with systemic lupus erythematosus:
      relationship with disease duration.
AB  - The Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology (SLICC/ACR) Damage Index is a validated instrument specifically
      designed to ascertain damage in SLE; this instrument has been applied mainly to
      Caucasians and African-American SLE patients. The objective of this study was to
      assess damage using the SLICC/ACR Damage Index in Mexican SLE patients. The
      SLICC/ACR Damage Index was applied to 210 consecutive SLE patients with disease
      of variable duration. The SLICC/ACR Damage Index was assessed by review of
      hospital clinical records, interview and physical examination. One hundred and
      seventeen (55.5%) patients had some damage. The proportion of patients with
      damage increased significantly with disease duration (33% at 1-60 months, 66% at
      61-120 months and 70% at > or = 121 months, P < 0.001). The main organ systems
      involved were musculoskeletal (osteonecrosis), neuropsychiatric (neuropathy,
      seizures), gonadal (amenorrhea prior to age 40 years), ocular (cataracts), renal
      (glomerular filtration < 50%) and peripheral vascular (permanent damage by venous
      thrombosis). Damage was frequent, increased over time, particularly for ocular,
      renal, musculoskeletal and gonadal. Patients who experienced damage were older,
      had a longer disease duration, a greater number of ACR criteria at diagnosis, and
      were more likely to have renal involvement and antibodies to dsDNA. The damage
      occurred in many different domains and started to develop early after disease
      onset. Mexican patients had more peripheral vascular and gonadal involvement
      compared with published data from non-Hispanic SLE populations.

PMID- 9580343
TI  - Effect of prostaglandin F2 alpha on seasonality of swine reproduction.

PMID- 9580344
TI  - A comparative study of ofloxacin and ciprofloxacin erythrocyte distribution.
AB  - The present work deals with the in vitro and in vivo distribution of ofloxacin
      and ciprofloxacin in erythrocytes. In vitro studies were carried out in standard
      solutions prepared using fresh blood for a concentration range between 100 and
      0.25 micrograms mL-1. A 5 mg kg-1 bolus dose was administered to rabbits and
      erythrocyte and plasma kinetics were determined over 8 h. A linear model was used
      to establish the relationship between plasma and erythrocyte concentrations of
      both quinolones in vitro. The mean partition coefficient values obtained were
      1.04 +/- 0.02 and 1.32 +/- 0.03 for ofloxacin and ciprofloxacin, respectively. A
      decrease in the ciprofloxacin partition coefficient was observed at higher
      concentrations. Values ranged between 2.54 +/- 0.40 and 1.38 +/- 0.15 as the
      concentrations increased. The partition coefficients obtained from the linear
      relationship between plasma and erythrocyte concentrations established from the
      in vivo data were 0.80 +/- 0.58 for ofloxacin and 0.61 +/- 0.30 for
      ciprofloxacin. In vivo plasma and erythrocyte data analysis was performed by a
      deconvolution method and the theoretical transfer curves in erythrocytes were
      estimated. The distribution of both quinolones to erythrocytes is very rapid,
      probably due to a high permeability of erythrocyte membranes to these drugs. This
      was also confirmed by the parallelism between plasma and erythrocyte kinetics.

PMID- 9580345
TI  - Treatment of T prolymphocytic leukemia with allogeneic bone marrow
      transplantation.
AB  - T prolymphocytic leukemia (T-PLL) is an unusual disease characterized by high
      white cell counts, older age at presentation, splenomegaly and a very aggressive
      clinical course. We describe a 47-year-old male with refractory T-PLL who was
      treated with high-dose chemoradiotherapy and allogeneic bone marrow
      transplantation (BMT) from an HLA-matched sibling. The transplant was complicated
      by both acute and chronic graft-versus-host disease (GVHD). The patient achieved
      complete remission and remains in remission 3 years after the transplant.

PMID- 9580346
TI  - Mechanisms underlying the transport and intracellular metabolism of acetic acid
      in the presence of glucose in the yeast Zygosaccharomyces bailii.
AB  - Zygosaccharomyces bailii ISA 1307 displays biphasic growth in a medium containing
      a mixture of glucose (0.5%, w/v) and acetic acid (0.5%, w/v), pH 5.0 and 3.0. In
      cells harvested during the first growth phase, no activity of a mediated acetic
      acid transport system was found. Incubation of these cells in phosphate buffer
      with cycloheximide for 1 h restored activity of an acetic acid carrier which
      behaved as the one present in glucose-grown cells. These results indicated that
      the acetic acid carrier is probably present in cells from the first growth phase
      of the mixed medium but its activity was affected by the presence of acetic acid
      in the culture medium. In glucose-grown cells, after incubation in phosphate
      buffer with glucose and acetic acid, the activity of the acetic acid carrier
      decreased significantly with increased acid concentration in the incubation
      buffer. At acid concentrations above 16.7 mM, no significant carrier activity was
      detectable. Furthermore, the intracellular acid concentration increased with the
      extracellular one and was inversely correlated with the activity of the acetic
      acid carrier, suggesting the involvement of a feedback inhibition mechanism in
      the regulation of the carrier. During biphasic growth, the first phase
      corresponded to a simultaneous consumption of glucose and acetic acid, and the
      second to the utilization of the remaining acid. The enzyme acetyl-CoA synthetase
      was active in both growth phases, even in the presence of glucose. Activity of
      isocitrate lyase and phosphoenolpyruvate carboxykinase was found only in acetic
      acid-grown cells. Thus it appears that both membrane transport and acetyl-CoA
      synthetase and their regulation are important for Z. bailii to metabolize acetic
      acid in the presence of glucose. This fact correlates with the high resistance of
      this yeast to environments with mixtures of sugars and acetic acid such as those
      often present during wine fermentation.

PMID- 9580347
TI  - [Aortic balloon valvuloplasty as a bridge to definitive therapy of severe aortic
      stenosis].
AB  - In a 36-year-old man with severe aortic stenosis and refractory cardiogenic
      shock, an emergency percutaneous balloon aortic valvuloplasty was performed,
      followed by clinical improvement, allowing elective aortic valve replacement at
      the 48th day post-valvuloplasty. Clinical follow-up for eight months after
      surgery showed significant functional improvement. Aortic balloon valvuloplasty
      is a life-saving approach to patients with severe aortic stenosis and high
      surgical risk and should be considered as a bridge to planned valve replacement
      or cardiac transplantation. Aortic valve replacement should be considered even in
      patients with severe ventricular dysfunction, while the cardiac transplantation
      should be indicated for patients with a very marked and irreversible depression
      of myocardial contractility.

PMID- 9580348
TI  - Creation of transjugular intrahepatic portosystemic shunts with use of the Cragg
      Endopro System I.

PMID- 9580350
TI  - Behavioral and monoaminergic changes after lindane exposure in developing rats.
AB  - The effects of lindane on behavior and central monoaminergic systems were studied
      in rat pups at 15 days of postnatal age. Pups were previously given nonconvulsant
      lindane PO doses, either a single 20 mg/kg or 7-day repeated 10 mg/kg doses. Both
      treatment schedules improved the passive avoidance acquisition but only the acute
      administration prolonged the step-through latency. Acute lindane decreased the
      motor activity, whereas the repeated dosing increased it. Increases of the ratio
      5-HIAA/serotonin in several brain regions and of the ratio DOPAC/dopamine in the
      mesencephalon after a single dose of lindane suggest an enhanced monoaminergic
      turnover. In contrast, repeated lindane doses decreased monoamine/metabolite
      ratios excluding the striatum, where an increase of DOPAC/dopamine ratio
      correlates with the higher motor activity of these animals. It is postulated that
      both the imbalance of the central monoaminergic systems and the lindane-induced
      GABAergic blockade may be the basis of the behavioral alterations.

PMID- 9580349
TI  - Usefulness of videoduodenoscopy and vital dye staining as indicators of mucosal
      atrophy of celiac disease: assessment of interobserver agreement.
AB  - BACKGROUND: The present study was designed to determine the diagnostic usefulness
      of videoduodenoscopic inspection alone and the addition of vital dye staining in
      the detection of celiac disease. We additionally sought to evaluate interobserver
      agreement for specific duodenoscopic markers of mucosal atrophy. METHODS: One
      hundred sixty-seven consecutive subjects who underwent duodenoscopy for
      intestinal biopsy were included in a prospective controlled study. Endoscopic
      examination was performed by experienced endoscopists according to a set protocol
      using methylene blue (1%) dye. All procedures were recorded on videotape, but
      only 20 (10 with atrophy and 10 normal) were used in a blinded, independent,
      randomized analysis by five reviewers to evaluate interobserver agreement.
      Endoscopic signs indicative of mucosal atrophy were as follows: reduction in the
      number or loss of Kerkring's folds, "scalloped" folds, "mosaic pattern," and
      visualization of the underlying blood vessels. RESULTS: Eighty-seven patients had
      celiac disease (57 newly diagnosed, 30 when treated). Seven treated patients had
      nonatrophic mucosa. In 80 patients the final diagnosis excluded celiac disease.
      Videoendoscopic inspection alone correctly identified 75 of 80 patients with
      complete mucosal atrophy and 86 of 87 with normal mucosa. False-negative
      diagnoses occurred in treated celiac patients with mild atrophy. Mosaic pattern
      (89%) and scalloped folds (86%) were the most useful endoscopic signs. Vital dye
      staining, as assessed by experienced endoscopists, provided identical results to
      those obtained by inspection alone. Sensitivity, specificity, and positive and
      negative predictive values for the presence of one or more than one feature were
      94%, 100%, 100%, and 96%, respectively. The agreement (kappa statistics) among
      observers was excellent for the mosaic pattern (kappa: 0.76 for both the
      videoendoscopic inspection alone and dye staining) and the scalloped folds
      (kappa: 0.83 and 0.76, respectively) and was fair (kappa: 0.41 and 0.59,
      respectively) for the reduction in the number or loss of duodenal folds.
      CONCLUSION: This study confirms that videoduodenoscopy is useful in the detection
      of intestinal atrophy. Dye staining produces a better delineation of scalloped
      folds and mosaic pattern in the atrophic mucosa, but did not provide additional
      information to the expert endoscopist. Finally, interobserver agreement was
      excellent for the most prevalent signs.

PMID- 9580352
TI  - [Vertigos in childhood. Characteristics according to our results].
AB  - The paper deals with a review of 25 cases of infantile dizziness done for a term
      of 10 years. The protocol employed in the study, the characteristics and the
      follow-up of the crises are contemplated.

PMID- 9580351
TI  - [Outpatient ENT hospital emergencies: a descriptive study of one year of
      services].
AB  - A descriptive and retrospective scrutiny dealing with 2,638 emergency cases
      admitted at "Virgen de la Salud" Hospital, Toledo, during 1993. Analysis of a
      series of parameters as age, sex, hour, day of the week, month, kind of
      pathology, emergency ward in charge of the exigency and so on, and correlation of
      these items. Assessment of the gravity of each urgent case and motive of
      admission. Our results are confronted with those given by other authors.

PMID- 9580353
TI  - [Hyperandrogenic ovary syndrome].

PMID- 9580354
TI  - [Evaluation of the efficacy of psychoeducative groups in schizophrenic patients].
AB  - One of the main difficulties we find in psychopharmacologic treatment of
      schizophrenia is medication compliance. Following Kissling, only 40-50% of
      patients adequately follow prescription directions. This phenomenon becomes one
      of the major factors of the high relapse rates in schizophrenia. Several studies
      have been made in recent oriented to improve medication compliance through
      psychoeducational groups involving patients and their closest relatives. Our
      results confirm the hypothesis. Statistically significant differences (p <
      0.0001) are found between readmission rates in control group (2.32%) and in group
      of patients participating in psychoeducational groups (0.30%). Significant
      differences are also found when considering separately first episode patients
      (1.61% controls vs. 0.04% cases, p < 0.0001) and patients with previous history
      (3.05% controls vs. 0.61% cases, p < 0.0001).

PMID- 9580355
TI  - [Evaluation of the impact of early retirement on the quality of life].
AB  - AIM: To evaluate the impact of early retirement, quality of life and general
      health level of a sample of industrial workers. SUBJECTS: 78 early retired
      industrial workers were evaluated on two separate occasions, baseline and after
      three years. INSTRUMENTS: A sociodemographic and clinical "ad hoc" protocol and
      the Spanish versions ot the following scales: the Quality of Life Questionnaire
      (1) the GHQ-28 (2, 3) and the MMSE (4, 5), the Self-Concept Scale (6, 7) and the
      Depression-Anxiety Scale from Goldberg (8-10). RESULTS: Those retired for
      physical or accident purpose showed a worse self-image and greater levels of
      anxiety CONCLUSIONS: Being retired for physical or accident purpose plays a
      significant role in the development of psychopathology.

PMID- 9580357
TI  - [Risk stratification and prognosis in critical surgical patients using the Acute
      Physiology, Age and Chronic Health III System (APACHE III)].
AB  - INTRODUCTION: Outcome prediction in critical surgical patients admitted to
      intensive care units (ICU) has been established using several scoring systems. To
      evaluate the predictive performance of the Acute Physiology, Age and Chronic
      Health Evaluation (APACHE III) scoring system in these patients, we studied a
      population admitted to a surgical ICU in our University Hospital. METHODS: We
      collected prospective data on 220 consecutive patients admitted over a period of
      12 months. APACHE III (A3) scores were obtained over the first 24 hours of ICU
      admission (APACHE II scores were also calculated); data also included age, sex,
      acute and chronic diseases, ICU and hospital length of stay (LOS), patient
      location prior to ICU admission and outcome. The relationship of hospital
      mortality with A3 scores was analyzed using logistic regression, with the
      discriminatory power of these systems being assessed by the area under the ROC
      curve and percentage of correct classification. RESULTS: Patient's mean age was
      57 +/- 17 years and 44% were male; 53.6% were elective and 46.4% were emergency
      postoperative patients; 5% of patients had co-morbidities; ICU mortality rate was
      10% and in-hospital mortality rate (HMR) was 15%; mean ICU LOS was 3.9 +/- 5.6
      days and mean hospital LOS was 9.4 +/- 8.2 days; mean scores were: APACHE III =
      33 +/- 2 and APACHE II = 9 +/- 6 points. There was a significant relationship
      between ascending A3 scores and HMR. APACHE III had a correct classification rate
      of 87.3% and an area under the ROC curve of 0.830. CONCLUSIONS: In a population
      of critical surgical patients admitted to our ICU the APACHE III scoring system
      demonstrated an excellent prognostic performance as measured by contingency
      tables and areas under the ROC curve; this system can be a useful tool for
      outcome prediction in critical surgical patients.

PMID- 9580358
TI  - [Analysis of blood utilization in programmed surgery].
AB  - The purpose of this study is to analyse the crossmatched blood units for elective
      surgery and the real amount of transfused blood, the crossmatch:transfusion rate
      (C:T) which must be less than 2.5. As in other Blood Banks, the differences are
      more evident in the situations in which the need for blood is very small, the so
      called "Type and Screen".

PMID- 9580356
TI  - [Pseudoneurologic conversion and factitious disorders: differential diagnosis in
      2 clinical cases].
AB  - The recognition and differentiation of conversion and factitious disorders could
      be difficult when they coexist with physical problems and their psychopathology
      is not evident. We present two illustrative cases of patients who share the
      existence of neurological disorders and present a similar psychiatric semiology,
      which is phenomenologically different related with their physical deficits. The
      psychopathological assessment was made by means of a standardized instrument for
      diagnosis (SCAN) and suitable paraclinical techniques for each case. The test
      MMPI (Minnesota Multiphasic Personality Inventory) was used in both cases, and an
      exploration with Thiopental was carried out in one of them. The pertinent
      differential diagnosis, the advantages of coordinated interdisciplinary
      interventions in order to elucidate these mental disorders, and the convenience
      of using appropriated psychometric instruments and exploratory methods are
      expounded in the present paper.

PMID- 9580359
TI  - [Hypothyroid coma and thyrotoxic crisis].
AB  - Two clinical cases of endocrinologic emergency are presented: myxedema coma and
      thyrotoxic crisis. These are very severe situations with a high mortality rate.
      In myxedema coma it reaches 50% and in thyrotoxic crisis the range is between 25
      and 30%. These entities are not the always present in mind because of their
      rarity. Consequently, they may well be undiagnosed. In our cases, the myxedema
      coma was initially diagnosed as brainstem stroke, and the hyperthyroidism was
      taken for concealed malignant tumor. The management of both situations is briefly
      commented.

PMID- 9580360
TI  - [Intermittent claudication. Review of a disease of growing prevalence. I.
      Clinical aspects, etiology, epidemiology, natural history and diagnosis].

PMID- 9580361
TI  - [Airway management in ICU patients with mechanical ventilation].
AB  - A prospective protocol for the management of the airway was applied to patients
      in the ICU. Acute complications due to intubation and tracheotomy as well as
      laryngo-tracheal lesions were studied in 125 consecutive patients during one year
      from the moment of extubation. Thirty four cases (27%) needed reintubation, and
      58 tracheotomies were performed (46%). The average length of intubation was of 10
      +/- 7 days. Sixty five patients (53%) had acute complications due to intubation
      and 30 (52%) had acute complications due to the traccotomy. The high incidence of
      laryngo-tracheal lesions in the 85 patients who underwent early exploration (76
      cases [90%]) was reduced in those who underwent late exploration (11 cases
      [20%]). Analysis of possible prognostic factors in the development of late
      lesions allows us to affirm that a reduction in the length of intubation
      diminishes the presence of late lesions. We recommend the avoidance of oro
      tracheal intubation prolonged for more than 10 days by the early carrying out of
      tracheotomy.

PMID- 9580362
TI  - [Nodular heterotopia or central nervous system tumor].

PMID- 9580363
TI  - [Treatment of malignant ventricular arrhythmia guided by electrophysiologic
      study].
AB  - The purpose of this study was to assess the results of the treatment of malignant
      ventricular tachyarrhythmias guided by electrophysiologic studies. Thirty
      patients with ventricular arrhythmias, aged 56.6 +/- 14.1 years, were submitted
      to EP testing. The clinical presentation of arrhythmia was sustained monomorphic
      ventricular tachycardia in 24 (80%), non-sustained ventricular tachycardia in
      three and another three were survivors of sudden cardiac death. Twenty five
      patients (83%) had evidence of structural heart disease and left ventricular
      ejection fraction was less than 40% in 16 (53%). Antiarrhythmic drugs were
      considered effective when sustained monomorphic ventricular tachycardia was
      noninducible or significantly slowed in serial EP testing. Sustained monomorphic
      VT was induced in 19 patients (63%) and an effective drug therapy was found in 13
      (68%). In the other 11 patients sustained arrhythmias were not induced, although
      in six of them the study was done already under antiarrhythmic drugs, that were
      continued in the follow-up. In the six patients in which an effective drug
      regimen could not be found and in two sudden death survivors with primary
      ventricular fibrillation and negative EP testing, an Implantable Cardioverter
      Defibrillator was implanted. After 17.8 +/- 10.5 months, there was recurrence of
      the arrhythmia in 4 (18%) of the 22 patients on antiarrhythmic drugs and half of
      the patients with ICDs received appropriate therapy from the device. Three
      patients (10%) died in the follow-up, of which only one due to sudden death. We
      conclude that selection of optimal antiarrhythmic treatment based on the results
      of EP testing, is associated with decreased episode recurrence and sudden death.

PMID- 9580364
TI  - [Genetic diagnosis of familial adenomatous polyposis: detection of APC gene
      mutations based on an in vitro synthetized protein].
AB  - Familial adenomatous polyposis of the colon (FAP) is a dominant autosomic disease
      in which virtually 100% of the affected individuals develop colorectal cancer
      before the age of forty. The gene responsible for this disease (APC gene) is
      mutated in the germ line of these patients. The genetic diagnosis of FAP was
      initially done using linkage analysis. Because 95% of the mutations in APC gene
      result in a stop codon which will originate a truncated protein, previous authors
      have proposed that the mutation analysis should be performed using an in vitro
      synthesized protein (IVSP) assay. In this study we searched for germinal
      mutations in exon 15 of the APC gene in subjects belonging to families with FAP,
      using the IVSP assay. Eighty individuals belonging to 23 families were included
      in this series. We started by studying exon 15 which encompasses 6500/8535 bp and
      which corresponds to 75% of the coding region. This exon was divided into four
      fragments, which were amplified by PCR and the product was used in a
      transcription/translation assay. Mutations resulting in a truncated protein were
      detected in 9/23 (39%) of the families. This corresponds to 20/42 (48%) of
      individuals analysed in these nine families. All the mutations were located in
      the 5' region of exon 15, with seven of them being in the first fragment and the
      remaining two in the same place of the second fragment. With the exception of two
      healthy individuals at risk, all the others with a detected mutation, already
      exhibited clinical manifestations. One of these two individuals was later
      confirmed to harbor colonic polyps, strengthening the diagnostic accuracy of this
      IVSP analysis. We also identified 10 other healthy subjects at risk with a
      negative genetic diagnosis, who were therefore removed from surveillance
      programs. In conclusion, our results show that IVSP analysis has a high
      sensitivity as a diagnostic tool and should be used as the first screening method
      to identify those individuals who have inherited the genetic defect, even before
      they have developed any symptoms. This will enable us to try new drugs which may
      potentially delay or prevent the development of colonic polyps.

PMID- 9580365
TI  - [Lesions of erythema nodosum type as the only manifestation of brucellosis].

PMID- 9580366
TI  - Insulin sensitivity and insulin secretion in lean and obese normal pregnant
      women.
AB  - An insulin-modified frequently sampled intravenous glucose tolerance test with
      minimal model analysis was performed in normal pregnant women between 28-32 weeks
      of gestation, to assess insulin sensitivity and insulin secretion. Insulin
      sensitivity in the pregnant group (no. 26) was reduced to approximately 50% that
      of nonpregnant group (no. 27) (p < 0.05). This increased insulin resistance was
      compensated by an enhancement of the first phase of insulin secretion, which was
      increased more than twofold in the pregnant women when compared with the
      nonpregnant women (p < 0.05). There was a trend toward greater insulin resistance
      and insulin secretion in the obese pregnant women (no. 7) as compared with the
      lean pregnant women (no. 19) although this difference was not statistically
      significant. Our findings confirm that late pregnancy is a state of physiologic
      insulin resistance compensated by an increase of insulin secretion.

PMID- 9580367
TI  - Stimulation of insulin release in vivo by the methyl esters of succinic acid and
      glutamic acid.

PMID- 9580368
TI  - Beta cell replication and mass in islet transplantation.

PMID- 9580369
TI  - Nefazodone in major depression: adjunctive benzodiazepine therapy and
      tolerability.
AB  - One hundred sixty-six patients suffering from major depressive disorders were
      treated for 8 weeks with nefazodone in an open study in dosage ranges from 200 to
      600 mg. This report focuses primarily on the first week of therapy and on the
      concomitant use of several benzodiazepines, one of which is not metabolized by
      the cytochrome system (temazepam). Triazolam response was further evaluated as a
      function of two nefazodone dosage regimens provided during the first week of
      therapy, one group receiving nefazodone 200 mg/day for 7 days, and another group
      receiving nefazodone 200 mg/day for 3 days, followed by 4 days with 400 mg/day.
      Finally, a comparison of three different nefazodone dosages, the third being 400
      mg from day 1 on, was also carried out. Outcome measures included Hamilton Rating
      Scale for Depression total and the total of the three Hamilton Rating Scale for
      Depression insomnia items, as well as global improvement, a daily completed sleep
      questionnaire, and adverse event assessment. A combination of nefazodone with a
      benzodiazepine (BZ) caused more sedation than nefazodone alone; triazolam, the BZ
      with the shortest half-life and the highest dependence on the cytochrome 450
      system for its metabolism, caused the least amount of sedation, and alprazolam
      and diazepam, the two daytime benzodiazepines, caused the most sedation.
      Triazolam caused significant and identical reduction of insomnia in both
      nefazodone groups. Compared with nefazodone 200 mg given as monotherapy, insomnia
      was significantly improved--not only by triazolam, but also alprazolam and
      diazepam, but not temazepam. The addition of nefazodone raised triazolam plasma
      levels to almost 500%, the plasma level of desmethyl-diazepam 87%, and that of
      alprazolam 34%. Temazepam plasma levels remained unchanged. When prescribing
      nefazodone with a benzodiazepine, one should expect an improved sleep pattern
      initially, but at the cost of clinically relevant daytime sedation. The
      prediction that temazepam, the only BZ not dependent on the cytochrome mechanism
      for metabolism, should be the least sedating, and triazolam, because of its
      cytochromic metabolism interference with nefazodone should be the most sedating,
      could not be confirmed. In fact, triazolam 0.25 mg capsules seem to be the safest
      treatment of choice when one has to combine a benzodiazepine with nefazodone in
      initial stages of therapy, at least of the four benzodiazepines tested in this
      study.

PMID- 9580370
TI  - A retrospective study of kidney transplant recipients from living unrelated
      donors.
AB  - Due to the shortage of cadaveric organs, kidneys from living unrelated donors
      (LUD) are increasingly being used for transplantation. The long-term outcome for
      LUD recipients is not completely known. This study was undertaken to evaluate the
      long-term graft survival in LUD recipients and compare it with that of cadaver
      donor allograft recipients. Three hundred and sixty-four LUD and 3881 cadaveric
      kidney recipients were evaluated using data obtained through the Brazilian Renal
      Transplant Registry. Transplants performed between January 1, 1987, and June 30,
      1996, were eligible for analysis. Graft and patient survival were estimated by
      the Kaplan-Meier method. Sixty percent of the LUD were from spouses. The median
      duration of follow-up was 23.8 mo (0 to 117.2 mo). Patient survival rates were
      not significantly different for LUD and cadaveric kidney recipients (69% [95%
      confidence interval (CI), 61.9 to 76.1%] versus 73.2% [71 to 75.4%] at 5 yr; 69%
      [61.9 to 76.1%] versus 60.6% [55.1 to 66.1%] at 9.6 yr). Graft survival rates for
      recipients of LUD allografts were similar to those for cadaveric kidneys at 5 yr
      (50.1% [43.2 to 57%] versus 50.4% [48.1 to 52.8%]) and higher, although not
      significantly, at 9.6 yr (45.7% [37.7 to 53.7%] versus 32.7% [26.4 to 39%],
      respectively, P = 0.14). In a multivariate analysis using the Cox proportional
      hazards regression model, after adjusting for recipient age, race, history of
      previous transplantation, and year of transplantation, the risk of graft failure
      was 16% (95% CI, -3% to 31%) lower for LUD than cadaveric recipients. We conclude
      that LUD are an excellent alternative to cadaveric kidney donors. The long-term
      patient and graft survival rates for recipients of LUD allografts are at least as
      good as those for recipients of cadaveric kidneys.

PMID- 9580371
TI  - Prevention of rotavirus diarrhoea in foals by parenteral vaccination of the
      mares: field trial.
AB  - Many countries have reported rotavirus diarrhoea in foals. In Argentina it causes
      important economic losses to the horse industry. In this work we present the
      results obtained using an experimental vaccine in a farm with enzootic infection
      of rotavirus. A hundred mares were vaccinated 60 and 30 days before foaling with
      inactivated rotavirus SA11 (G3P2), H2 (G3P12), Lincoln (G6P1), with aluminum
      hydroxide as adjuvant; 65 mares were included in the unvaccinated, control group.
      To evaluate the vaccine, morbidity, duration of the diarrhoea and rotavirus
      shedding were recorded. Antibody levels were established in serum, colostrum and
      milk of the vaccinated mares, and also in serum from the foals. In foals from
      vaccinated mares the morbidity was 30%, clinical signs were observed during 1.8
      days, and rotavirus shedding was not detected. In the control group the morbidity
      reached 80%, the clinical signs lasted 7.3 days and rotavirus shedding was
      detected in 80% of the diarrhoeic foals. At foaling the serum antibody levels
      were 15 times higher with a mean neutralizing titre (NT) of 3.5 logs than before
      vaccination (2.4 logs), in colostrum 5.00 logs, and in milk at 90 days post
      partum 1.7 logs. In foals from vaccinated mares the level of neutralizing
      antibodies was 3.8 logs at 48 days of age, going down to 2.2 logs at 90 days of
      age. Immunization of the pregnant mare would be a good method for preventing
      diarrhoea in foals.

PMID- 9580372
TI  - Influence of several adjuvants on the immune response against a recombinant
      meningococcal high molecular weight antigen.
AB  - Studying outer membrane proteins as vaccine candidates, our group has previously
      isolated, cloned, and expressed in Escherichia coli the gene encoding for a high
      molecular weight protein (P64k), common to many meningococcal strains. To
      continue the characterisation of this meningococcal antigen, we have evaluated
      its immunogenicity in mice alone or combined with several commercially-available
      adjuvants. We used as an adjuvant aluminium hydroxide (Alhydrogel and
      Rehydragel), aluminium phosphate, Algammulin, crude saponin, the saponin Quil A,
      dimethyl-dioctadecyl ammonium bromide (DDA), Freund's adjuvant, and Montanide
      888. The antibody titres against the recombinant protein and whole meningococci
      elicited with these adjuvants were compared. We found that Quil A produced the
      highest titres against the recombinant P64k. Algammulin and the quaternary
      ammonium compound DDA induced the highest levels of antibodies against
      meningococci. We analysed the recognition of a set of linear peptides by antisera
      prepared against the protein combined with some of the adjuvants. The responses
      depended on the adjuvant used and the results have been confirmed by epitope
      mapping using overlapping peptides synthesised on pins.

PMID- 9580373
TI  - Quantitation of hepatitis C virus in liver and peripheral blood mononuclear cells
      from patients with chronic hepatitis C virus infection.
AB  - Since the natural history of hepatitis C virus-associated liver disease and the
      therapeutic responsiveness might vary according to liver and blood mononuclear
      cells viral levels, it may be important to quantitate viral RNA in liver, blood
      mononuclear cells and serum, and to compare these data with genotype, biochemical
      and histologic data. A polymerase chain reaction-based assay available for serum
      hepatitis C virus RNA quantitation has been optimized to quantitate viral genomes
      in liver and peripheral blood mononuclear cells from 47 chronic hepatitis C
      patients. The procedure permitted hepatitis C virus RNA quantitation in freshly
      isolated mononuclear cells and in total RNA extracted from frozen mononuclear
      cells and liver tissue. The intrahepatic viral amount (median: 2.6 x 10(3)
      copies/microgram RNA; range: 0 to 3.6 x 10(4) copies/microgram RNA) correlated
      significantly with the hepatitis C virus RNA concentration in serum (r = 0.76, P
      < .001), but not in mononuclear cells. Viral RNA concentrations in liver (P <
      .001), serum (P < 0.01) and PBMC (P < 0.05) were significantly higher in
      hepatitis C virus genotype 1 patients (essentially type 1b) than in non-1 type
      cases, but were unrelated to biochemical or histologic indexes of disease
      activity. In conclusion, the optimized assay permit HCV RNA quantitation in liver
      and peripheral blood mononuclear cells, suggesting that serum viral level is an
      accurate measurement of intrahepatic viral burden.

PMID- 9580374
TI  - Preservative-free lidocaine 1% anterior chamber irrigation as an adjunct to
      topical anesthesia.
AB  - PURPOSE: To evaluate the effect on the central corneal endothelium of anterior
      chamber irrigation with preservative-free lidocaine 1% as an adjunct to topical
      anesthesia during phacoemulsification. SETTING: Department of Ophthalmology,
      Hospital Capuchos, Lisbon, Portugal. METHODS: This prospective, randomized
      controlled study comprised 59 eyes. Thirty-one eyes had phacoemulsification (in
      the-bag cracking technique) under topical anesthesia with anterior chamber
      irrigation by preservative-free lidocaine 1%. Twenty-eight eyes having the same
      procedure but with local-regional anesthesia served as the control group. All
      eyes had preoperative and postoperative specular microscopy and computer-assisted
      morphometry. A Student's t-test was used for between-group comparison of the
      following parameters: patient age, central corneal endothelial cell loss, mean
      endothelial cell size variation, and phacoemulsification ultrasound time Follow
      up was 4 weeks. RESULTS: The between-group differences in mean patient age and
      ultrasound time were not significant. The differences between groups in the
      endothelial cell parameters were also not significant. Mean postoperative
      endothelial cell loss was 3.59% +/- 2.79 (SD) in the topical anesthesia group and
      4.37 +/- 2.00% in the control group. Mean variation in cell size was 3.71 +/-
      1.57% and 3.79 +/- 1.07%, respectively. CONCLUSION: Intracameral infusion of
      preservative-free lidocaine 1% had no effect on the corneal endothelial cell loss
      rate or mean cell size variation in this short-term assessment.

PMID- 9580375
TI  - Alpha-1 antichymotrypsin levels are actively increased in normal colostrum.
AB  - BACKGROUND: It is well known that human colostrum has important antiinflammatory
      functions. The purpose of the current study was to determine antiprotease levels
      in colostrum and serum and to assess the importance of local synthesis and the
      electrophoretic differences in both locations. METHODS: Five protease inhibitors
      were determined by radical immunodiffusion in colostrum and serum samples taken
      simultaneously from 50 healthy women, 36 to 72 hours after delivery. RESULTS:
      Antithrombin II, inter-alpha trypsin inhibitor, and alpha-2 macroglobulin levels
      were undetectable in colostrum. Mean antitrypsin levels in colostrum were 6% of
      serum levels, but colostrum alpha-1 antichymotrypsin was higher than expected
      (0.39+/-0.34 g/l) in relation according to the albumin passive transport, and
      their mean value was 41% of serum levels. Colostrum antichymotrypsin levels did
      not correlate with serum antichymotrypsin levels or with colostrum albumin
      levels. The antichymotrypsin molecule in colostrum had a slower electrophoretic
      mobility when compared with that of serum antichymotrypsin, and it showed a
      different pattern in Western blot analysis, with a predominating 80-kDa molecule.
      CONCLUSIONS: Although the origin of colostral antichymotrypsin is unclear, local
      production in breast epithelial cells is likely. Antichymotrypsin is increased in
      colostrum, and its molecule has some characteristic differences, suggesting that
      it has an important and specific role in infant nutrition during breast milk
      feeding.

PMID- 9580376
TI  - Evaluation of an extensively hydrolyzed casein-whey protein formula in immediate
      cow's milk protein hypersensitivity.
AB  - BACKGROUND: Hydrolysate formulas are safe for most infants who are allergic to
      cow's milk. The purpose of this study was to assess the clinical tolerance and
      safety of an extensively hydrolyzed casein-whey protein formula in a homogeneous
      group of patients with immediate cow's milk hypersensitivity. METHODS: The study
      population consisted of 33 infants in whom immediate cow's milk protein allergy
      had been diagnosed by clinical data, evidence of specific immunoglobulin E
      antibodies, and positive results in a controlled challenge test with cow's milk
      proteins. RESULTS: The hydrolysate was well tolerated in 31 of the 33 patients,
      which represented a 94% effectiveness. Using 95% confidence intervals generated
      for a binomial outcome (reaction-no reaction), the casein-whey protein formula is
      tolerated by 84.4% to 99% of infants with immediate immunoglobulinE-mediated
      cow's milk protein allergy. These figures are in the range of values recommended
      for this type of product. CONCLUSIONS: This extensively hydrolyzed casein-whey
      protein formula is generally safe to feed children with immediate
      hypersensitivity to cow's milk. However. it is advisable that the first intakes
      be given under direct medical supervision, in that the occurrence of adverse
      reactions in highly sensitive infants cannot be unequivocally excluded.

PMID- 9580377
TI  - Endocardial and epicardial ablation guided by nonsurgical transthoracic
      epicardial mapping to treat recurrent ventricular tachycardia.
AB  - INTRODUCTION: An epicardial site of origin of ventricular tachycardia (VT) may
      explain unsuccessful endocardial radiofrequency (RF) catheter ablation. A new
      technique to map the epicardial surface of the heart through pericardial puncture
      was presented recently and opened the possibility of using epicardial mapping to
      guide endocardial ablation or epicardial catheter ablation. We report the
      efficacy and safety of these two approaches to treat 10 consecutive patients with
      VT and Chagas' disease. METHODS AND RESULTS: Epicardial mapping was carried out
      with a regular steerable catheter introduced into the pericardial space. An
      epicardial circuit was found in 14 of 18 mapable VTs induced in 10 patients.
      Epicardial mapping was used to guide endocardial ablation in 4 patients and
      epicardial ablation in 6. The epicardial earliest activation site occurred 107+/
      60 msec earlier than the onset of the QRS complex. At the epicardial site used to
      guide endocardial ablation, earliest activation occurred 75+/-55 msec before the
      QRS complex. Epicardial mid-diastolic potentials and/or continuous electrical
      activity were seen in 7 patients. After 4.8+/-2.9 seconds of epicardial RF
      applications, VT was rendered noninducible. Hemopericardium requiring drainage
      occurred in 1 patient; 3 others developed pericardial friction without
      hemopericardium. Patients remain asymptomatic 5 to 9 months after the procedure.
      Interruption during endocardial pulses occurred after 20.2+/-14 seconds (P =
      0.004), but VT was always reinducible and the patients experienced a poor
      outcome. CONCLUSION: Epicardial mapping does not enhance the effectiveness of
      endocardial pulses of RF. Epicardial applications of RF energy can safely and
      effectively treat patients with VT and Chagas' disease.

PMID- 9580378
TI  - Preparation of a monoclonal antibody specific for the class I isotype of beta
      tubulin: the beta isotypes of tubulin differ in their cellular distributions
      within human tissues.
AB  - Tubulin, the subunit protein of microtubules, is an alpha/beta heterodimer. In
      many organisms, both alpha and beta consist of various isotypes. Although the
      isotypes differ in their tissue distributions, the question of whether the
      isotypes perform different functions in vivo is unanswered. In mammals, the betaI
      and betaIV isotypes are quite widespread, and betaII is less so, while betaIII
      and betaVI have narrow distributions and betaV distribution is unknown. As a tool
      for localizing the isotypes, we report the preparation of a monoclonal antibody
      specific for betaI, to add to our previously described monoclonal antibodies
      specific for betaII, betaIII, and betaIV [Banerjee et al., J. Biol. Chem.
      263:3029-3034, 1988; 265:1794-1799, 1990; 267:5625-5630, 1992]. In order to
      prepare this antibody, we have purified betaI-rich rat thymus tubulin. We have
      used our battery of antibodies to localize the beta isotypes in four human
      tissues: oviduct, skin, colon, and pancreas. We have found striking differences
      in their tissue distributions. There is little or no betaIII in these tissues,
      except for the columnar epithelial cells of the colon. BetaII is restricted to
      very few cells, except in the skin, where it is concentrated in the stratum
      granulosum. BetaI is widespread in all the epithelia. In the skin it is found in
      the entire stratum malpighii. In the oviduct, betaI is found largely in the
      nonciliated epithelial cells. In the exocrine pancreas, betaI occurs only in the
      centroacinar cells and not in the acinar cells; the latter do not stain with any
      of these antibodies. BetaIV is present at very low levels in skin and pancreas.
      By contrast, it is prominent in the colon and also in the oviduct, where it
      occurs in all the epithelial cells, especially in the ciliated cells, with the
      highest concentrations in the cilia themselves. These results suggest that the
      regulation of the expression and localization of isotypes in tissues is very
      complex.

PMID- 9580379
TI  - Structural and functional aspects of cardosins.

PMID- 9580380
TI  - Crystallisation, structure solution, and initial refinement of plant cardosin-A.

PMID- 9580381
TI  - Infant random dot stereoacuity cards.
AB  - PURPOSE: The overall goal was to develop a simple test of random dot stereoacuity
      that can be used during the first 24 months of life to measure sensory outcomes
      following treatment of ophthalmopediatric disorders, both in the context of
      clinical trials and in the context of clinical management. METHODS: A series of
      random dot stereoacuity test cards were constructed using vectographic vertical
      bar stimuli with crossed disparities ranging from 1735 to 45 sec. A two
      alternative, forced-choice, preferential-looking test protocol was used to
      measure stereoacuity in 95 healthy term infants (173 tests) over the 1.5-to-24
      month age range. Success rate, validity, and tolerance limits for normal
      performance as a function of age were evaluated. RESULTS: The success rate was
      high (158 of 173 tests; 91.3%). The maturation of random dot stereoacuity was
      similar to that measured in earlier lab-based preferential-looking and visual
      evoked potential protocols; few infants younger than 2 months of age demonstrated
      stereopsis although by 12 months, mean stereoacuity was 2.1 log sec (120 sec). A
      further improvement to 1.7 log sec (56 sec) was seen during months 18 to 24,
      consistent with data obtained in an earlier operant random dot protocol.
      Tolerance limits for normal ranged from approximately 1000 sec at 6 months to 100
      sec after 12 months. CONCLUSIONS: The infant random dot stereoacuity cards
      provide a simple, quick, and portable preferential-looking test of random dot
      stereoacuity for infants that has a high success rate and excellent concordance
      with stereoacuity outcomes from laboratory-based protocols.

PMID- 9580382
TI  - Spontaneous brain magnetic activity in schizophrenia patients treated with
      aripiprazole.
AB  - This magnetoencaphalographic (MEG) study was conducted as part of a multicenter
      clinical trial to study the efficacy of aripiprazole. Participants included 5 DSM
      IV schizophrenia subjects and 10 age-matched normal controls. The schizophrenia
      subjects underwent a second MEG recording after 8 weeks of open-label treatment
      with aripiprazole. Overall, control subjects showed no abnormal spontaneous
      magnetic brain activity. At washout, 3 patients showed increased delta and theta
      activity along with paraxosymal bitemporal slow waves. In 2 of these patients,
      the slow waves were generated in the superior temporal plane, as determined by
      dipole modeling. In the third patient, the slow waves appeared to have been
      generated at multiple regions throughout the temporal and inferior parietal
      lobes. As a group, schizophrenia patients, when compared with normal controls,
      demonstrated significant decreases in alpha peak frequency and power. Following
      treatment, aripiprazole had a significant normalizing effect on delta and theta
      activity. Patients on aripiprazole continued to demonstrate significant
      abnormalities in alpha frequency and power.

PMID- 9580383
TI  - Acute dissection of the thoracic aorta: experience at the Puerto Rico Medical
      Center (1991 through 1995)
AB  - BACKGROUND: Acute dissection of the thoracic aorta has a very poor prognosis
      unless promptly diagnosed and treated. The clinical presentation, diagnosis and
      management of 16 patients was reviewed. METHODS: We identified 12 patients from
      the Puerto Rico Medical Center and 4 patients from the "Centro Cardiovascular de
      Puerto Rico y del Caribe" whose diagnosis was made from January 1991 to December
      1995. Medical records and autopsy reports were reviewed. RESULTS: Of the 16
      patients, 10 [62%] were males, 10 [62%] were 60 years old or older [range 25 to
      85 years], and 15 [93%] had a past history of hypertension although only 6 [38%]
      were found with an initial blood pressure of 140/90 or higher. Chest pain was the
      initial symptom in 13 [81%]. Of these 46% [6/13] described it as oppressive, with
      radiation to back or neck in 38% [5/13]. In none a neurological abnormality was
      the initial presentation. No physical sign was present in more than 40% of
      patients. One patient had a diastolic murmur suggestive of aortic regurgitation
      but none had a pericardial rub or a neurologic deficit. The electrocardiogram
      showed left ventricular hypertrophy in 35% but none had changes compatible with
      an acute Q wave infarction. The chest radiography was compatible with dissection
      in all in whom it was done [8/8]. Computerized tomography of the chest was
      diagnostic in 6 of 8 patients [sensitivity 75%]. Aortography had a sensitivity of
      80% [4/5]. Trans-thoracic echocardiogram was diagnostic in 3 of 4 patients [75%
      sensitivity]. Transesophageal echocardiogram had a 100% sensitivity [2/2]. In 8
      patients [50%] the correct diagnosis was made by postmortem examination, all of
      whom died within 24 hours of Emergency Room's evaluation. Of those properly
      diagnosed 5 died without being surgically intervened. Only one survived surgery
      [1/3] Overall mortality was 93%. The most common pathological finding was Type A
      dissection in 14 [88%]. Cardiac tamponade was found in 9 [56%]. Hemothorax was
      found in 6 [38%]. Aortic valve insufficiency was reported in 20% and coronary
      artery involvement in 28%. CONCLUSIONS: The dismal prognosis traditionally
      associated with acute dissection of the thoracic aorta remains unchanged. Prompt
      diagnosis based on high clinical suspicion. followed by expeditious medical and
      surgical treatment are fundamental to change the natural course of this
      condition.

PMID- 9580384
TI  - Gastric emphysema simulating perforated hollow viscus: case report and review of
      literature.
AB  - Gastric emphysema is a benign condition in which air from non bacterial sources
      accumulate within the wall of the stomach. This pathology is usually associated
      with gastric and, or small bowel obstruction. A case report of gastric emphysema
      is presented, together with a pertinent review of the literature.

PMID- 9580385
TI  - Role of interferon alfa-2b in the induction and maintenance treatment of low
      grade non-Hodgkin's lymphoma: results from a prospective, multicenter trial with
      double randomization.
AB  - PURPOSE: To evaluate the effectiveness of adding interferon (IFN) alfa-2b to
      chemotherapy in the induction treatment of low-grade non-Hodgkin's lymphoma
      (NHL), and to assess the role of maintenance IFN. PATIENTS AND METHODS: A
      multicenter, two-phase controlled trial with double randomization was conducted
      in 155 patients with low-grade NHL. In the first randomization, 78 patients
      received cyclophosphamide, vincristine, and prednisone (CVP) and IFN, 3 MU/m2
      three times a week for 3 months, and 77 patients received CVP alone. Responding
      patients were randomized to receive IFN for 1 year versus observation. RESULTS:
      Of 144 assessable patients, 73 received CVP + IFN and 71 received CVP. Responses
      were similar: CVP + IFN 79% versus CVP 76% (P = .62). The number of patients who
      did not complete the treatment was higher in the CVP + IFN group than in the CVP
      group (18% v 4%; P = .009), although the received dose-intensity of chemotherapy
      was comparable. Duration of response and progression-free survival (PFS) were
      significantly higher in the CVP + IFN group than in the CVP group (P = .0004).
      However, we observed no differences in overall survival (OS) (P = .30), with a
      median follow-up for the surviving patients of 3 years. Grade 3/4
      granulocytopenia was the most frequent toxicity and was similar in both groups
      (33% v32%). Eighty-three (74%) of the 112 responding patients were randomized to
      maintenance IFN or observation. The duration of response was similar between 42
      patients that received IFN compared with 41 control patients (P = .83),
      independently of treatment previously administered. CONCLUSION: Adding IFN alfa
      2b to induction CVP in low-grade NHL did not induce a higher response rate, but
      it significantly increased the duration of the responses. We found significant
      differences in PFS that favored the patients who received CVP + IFN, but not in
      OS. To date, no additional benefit has been seen from the administration of IFN
      for maintenance.

PMID- 9580386
TI  - Influence of lipoprotein (a) levels and isoforms on fibrinolytic activity--study
      in families with high lipoprotein (a) levels.
AB  - Increased levels of lipoprotein (a) [Lp(a)] have been considered an independent
      risk factor for cardiovascular disease, but the mechanism behind this
      relationship is not completely understood. A high concentration of Lp(a) may
      interfere with fibrinolysis because of the structural similarity between apo(a)
      and plasminogen. The aim of the present study was to examine the influence of
      apo(a) levels and isoforms on fibrinolytic activity in 82 subjects from 24
      families in which the Lp(a) levels were > or =30 mg/dl in at least one child and
      one parent. Several fibrinolytic parameters, including plasmin generation by
      fibrin-bound tissue plasminogen activator, the lipid profile and apo(a) isoforms
      were studied. Subjects with high circulating Lp(a) levels (n = 44) had
      significantly reduced plasmin generation compared with their relatives with
      normal Lp(a) levels (n = 38). A significant inverse correlation between Lp(a)
      levels and plasmin generation was observed. The individuals with a combination of
      high levels of plasma Lp(a) and a major apo(a) isoform < or =580 kD molecular
      weight show the lowest fibrinolytic activity. A high correlation was found
      between the levels of apo(a) isoforms in children and the levels of the
      corresponding parental apo(a) isoforms. We conclude that the antifibrinolytic
      effect of Lp(a) in subjects with two apo(a) isoforms may depend not only on the
      total plasma level of Lp(a) but also on the relative concentration of the small
      apo(a) isoform.

PMID- 9580387
TI  - Modulation of rat striatal glutamatergic response in search for new
      neuroprotective agents: evaluation of melatonin and some kynurenine derivatives.
AB  - Melatonin attenuates the excitatory response of striatal neurons to sensorimotor
      cortex (SMCx) stimulation, which may be the basis for its neuroprotective role.
      Searching for new compounds with melatonin-like properties, the effects of
      several kynurenine derivatives in the response of the rat striatum to SMCx
      stimulation were studied using electrophysiological and microiontophoretical
      techniques. Melatonin iontophoresis (-100 nA) significantly attenuated the
      striatal excitatory response in 89.4% of the recorded neurons, showing excitatory
      properties in the other 10.6%. Compound A [2-acetamide-4-(3-methoxyphenyl)-4
      oxobutyric acid] (-100 nA) displayed similar attenuating effects (86.7% of
      neurons inhibited vs. 13.3% excited). Compound B [2-acetamide-4-(2-amine-5
      methoxyphenyl)-4-oxobutyric acid] (-100 nA) was more potent than melatonin itself
      to attenuate the excitatory response in 100% of the recorded neurons. Compound C
      [2-butyramide-4-(3-methoxyphenyl)-4-oxobutyric acid] (-100 nA) significantly
      increased the excitatory response in 84.2% of the recorded neurons, showing
      attenuating effects on the other 15.8% of the neurons. Interestingly, compound C
      iontophoresis excited the neurons in which melatonin had attenuating properties,
      whereas it inhibited the neurons showing excitatory responses to melatonin. These
      data suggest melatonin inverse agonist properties for compound C. Also, the
      effects of compounds B and C appeared immediately after they were
      iontophoretized, whereas both melatonin and compound A onset latencies were
      longer (2-4 min). The lack of latency shown by these melatonin analogs points to
      the possibility that melatonin itself was metabolized before producing its
      effects on striatal neurons. The results show a family of structurally-related
      melatonin analogs that may open new perspectives in search for new
      neuroprotective agents, including its clinical potentiality.

PMID- 9580388
TI  - Experimental hypercholesterolaemia in rabbits. Effect on lipid domains in
      homologous spermatozoa.
AB  - The distribution of membrane filipin sterol complexes (FSC) in the plasma
      membrane of the acrosomal region (PMAR) of rabbit sperm from epididymis and
      testis, in normal and hypercholesterolaemic rabbits, was examined at
      ultrastructural level. Membrane FSG were quantitatively analysed on freeze
      fracture replicas of filipin-treated cells. Cauda epididymal sperm shows a
      significant increase in filipin sterol complexes concentration in PMAR of
      hypercholesterolaemic animals compared to normal rabbits. Hypercholesterolaemic
      animals had 0.53 +/- 0.08 FSC micron-2 in the marginal segment of PMAR and 0.26
      +/- 0.03 FSC micron-2 for normal animals. In the principal piece we found 0.70 +/
      0.07 FSC micron-2 for hypercholesterolaemic and 0.43 +/- 0.03 FSC micron-2 for
      control animals. We also counted 0.58 +/- 0.04 FSC micron-2 in the equatorial
      segment of PMAR for hypercholesterolaemic and 0.38 +/- 0.03 FSC micron-2 for
      normal animals respectively. The FSC concentration of testicular sperm, like
      sperm from corpus and caput of epididymis in hypercholesterolaemic animals, did
      not differ from the controls. Cholesterol, phospholipids and
      cholesterol:phospholipid ratio in caudal epididymal sperm from treated males did
      not differ from controls. Only the sphingomyelin concentration decreases in cauda
      epididymal sperm from hypercholesterolaemic males compared to controls. The
      results presented in this paper suggest that the lipidic domains in PMAR of
      hypercholesterolaemic rabbits changes when the gametes go through the epididymis.

PMID- 9580389
TI  - Changes in the redox state in the retina and brain during the onset of diabetes
      in rats.
AB  - Diabetic retinopathy is thought to result from chronic changes in the metabolic
      pathways of the retina. Hyperglycemia leads to increased intracellular glucose
      concentrations, alterations in glucose degradation and an increase in
      lactate/pyruvate ratio. We measured lactate content in retina and other ocular
      and non-ocular tissues from normal and diabetic rats in the early stages of
      streptozotocin-induced diabetes. The intracellular redox state was calculated
      from the cytoplasmic [lactate]/[pyruvate] ratio. Elevated lactate concentration
      were found in retina and cerebral cortex from diabetic rats. These concentrations
      led to a significant and progressive decrease in the NAD+/NADH ratio, suggesting
      that altered glucose metabolism is an initial step of retinopathy. It is thus
      possible that tissues such as cerebral cortex have mechanisms that prevent the
      damaging effect of lactate produced by hyperglycemia and/or alterations of the
      intracellular redox state.

PMID- 9580391
TI  - 13C-urea breath test for the diagnosis of Helicobacter pylori infection. A
      further simplification for clinical practice.
AB  - BACKGROUND: The 13C-urea breath test is the most accurate noninvasive method for
      the diagnosis of Helicobacter pylori infection. The oral administration of citric
      acid solution as test drink 10 min before administration of 13C-urea appears to
      be the most valuable test procedure hitherto reported. To simplify the test for
      clinical routine, we evaluated in a prospective, randomized, crossover study the
      accuracy of a new modification that consists in giving the 13C-urea dissolved in
      the test drink. METHODS: Forty dyspeptic patients were studied. H. pylori status
      was assessed by histology, rapid urease test, and culture. A 13C-urea breath test
      was performed on 2 consecutive days by giving 200 ml 0.1N citric acid solution
      either 10 min previous to (protocol 1) or simultaneously with (protocol 2) the
      administration of 75 mg 13C-urea in randomized order. The 13CO2/12CO2 ratio was
      measured in breath samples taken before and 10, 20, 30, 45, and 60 min after
      administration of 13C-urea. RESULTS: Twenty patients were H. pylori-positive. In
      these subjects maximal delta values (28.1 per thousand (21.4-34.9) versus 30.6
      per thousand (22.8-38.4)), expired cumulative amount of 13C (9.3% (6.9-11.7)
      versus 10.2% (7.4-12.9)), and time to maximal delta value (33 min (26-39) versus
      35 min (29-42)) obtained by applying test protocols 1 and 2, respectively, were
      similar. Both test protocols provided negative results in all H. pylori-negative
      subjects. The 13C-urea was stable in citric acid solution at room temperature for
      at least 2 weeks. CONCLUSIONS: The 13C-urea breath test for the diagnosis of H.
      pylori infection can be simplified by giving the substrate dissolved in the test
      drink. This modification is not associated with a loss of diagnostic accuracy.

PMID- 9580390
TI  - Carbachol-induced hydrolysis of phospholipids in hippocampal slices may be
      mediated in part by subsequent activation of metabotropic glutamate receptors.
AB  - We observed that AP-3, an antagonist of metabotropic glutamate receptors, reduced
      carbachol-induced hydrolysis of phospholipids in hippocampal slices. This
      inhibition could be explained in different ways, e.g.: 1) AP-3 acts also as
      antagonist of muscarinic receptors mediating the hydrolysis of phospholipids
      induced by carbachol, 2) Carbachol induces the release of glutamate which, by
      activating metabotropic glutamate receptors, leads to additional hydrolysis of
      phospholipids. The aim of this work was to test these possibilities. It is shown
      that AP-3 reduces carbachol-induced hydrolysis of phospholipids in hippocampal
      slices but not in cerebellar neurons at 10-14 days of culture, when these cells
      are not able to induce hydrolysis of phospholipids following activation of
      metabotropic glutamate receptors. It is also shown that carbachol induces a
      release of [3H]aspartate in hippocampal slices. The results reported suggest that
      the hydrolysis of phospholipids induced by carbachol in hippocampal slices would
      have two components. One part would be due to direct activation by carbachol of
      muscarinic receptors associated to activation of phospholipase C. This part would
      not be inhibited by AP-3. The second part would be due to subsequent release of
      glutamate and activation of metabotropic glutamate receptors. This part would be
      inhibited by AP-3.

PMID- 9580392
TI  - In vitro quantitative assessment of enamel microhardness after exposure to
      eroding immersion in a cola drink.
AB  - Studies assessing the erosive potential of soft drinks have employed long time
      intervals of immersion that may not accurately depict the impact of frequent soft
      drink consumption on enamel. This in vitro study assessed the effect of a cola
      drink on enamel, replicating an actual drinking pattern. Six groups of 4 human
      enamel slabs were immersed (5 min each bath) in fresh cola drink, with immersions
      taking place with or without agitation, and under 3 regimes of frequency intake
      (low intake, 1 immersion/day; medium, 5/day; high, 10/day). Quantitative
      assessments of surface erosion were done over an 8-day interval using surface
      microhardness testing (Vickers). Results showed a sharp decrease from baseline
      (mean value 352.1 Vickers Hardness Number, SD 32.5) to day 1 (269.3, SD 41.0) and
      then continued decreasing throughout the assay, although less markedly, to reach
      204.5, SD 45.4 on day 8. Microhardness decreased regardless of frequency regime,
      except on day 8, on which slabs from the low intake group were harder (233.2, SD
      25.0) than slabs from the high intake group (169.8, SD 49.5; p < 0.05). Results
      from the ANOVA on the factorial experiment indicated that the role of agitation
      was statistically significant (d.f. = 1, F = 7.2, p = 0.020) while the level of
      intake was of borderline significance (d.f. = 2, F = 3.2, p = 0.075). The main
      effect resulting from the joint roles of agitation and intake indicated that
      there was an important interaction between the two variables (d.f. = 3, F = 4.5,
      p = 0.023).

PMID- 9580393
TI  - [Isotopic ventriculography in patients with obstructive hypertrophic
      cardiomyopathy treated with dual chamber stimulation].
AB  - BACKGROUND: Dual pacing stimulation improves symptoms and reduces
      intraventricular pressure gradient in obstructive hypertrophic cardiomyopathy.
      The mechanisms proposed for these effects are a change in ventricular contraction
      sequence, a paradoxical movement of the interventricular septum and a reduction
      in ventricular contractility. However, dual chambers pacing stimulation effects
      on systolic and diastolic function are unknown, and the study of this is the aim
      of this work. PATIENTS AND METHODS: We performed a radionuclide ventriculography
      in 10 patients with obstructive hypertrophic cardiomyopathy at 2 days and 1 and 6
      months after placing a dual chamber pacemaker. The phase images, ventricular
      volumes, left ventricular ejection fraction and segmentary contractility were
      evaluated. Diastolic maximum peak-filling-rate and time to-peak-filling-rate were
      also studied. RESULTS: In DDD pacing stimulation, parametric phase images show a
      reversal up-down contraction sequence starting from the apical segment. At 6
      months radionuclide ventriculography, a reduction in ejection fraction was found
      (60.9 +/- 12 vs 73.4 +/- 9.1; p < 0.05) which was attributed to apical, apical
      septum and mainly basal-septum segmentary contraction decrease. A paradoxical mid
      systolic septum movement was also found during DDD stimulation. No differences on
      diastolic parameters were noted. CONCLUSION: During dual chamber stimulation, a
      reversal ventricular contraction sequence, a paradoxical septum movement,
      hypokinesis of the septal ventricular segments and a reduction on left
      ventricular ejection fraction was observed.

PMID- 9580394
TI  - [Evaluation of left ventricular contraction using heart tomography with
      technetium 99m tetrofosmin in synchrony with ECG. Correlation with bidimensional
      echocardiography].
AB  - BACKGROUND: Echocardiography is a standard method of evaluating segmental and
      global left ventricular function in clinical practice. The aim of this study was
      to determine if segmental and global ventricular function determined from Gated
      SPECT myocardial imaging adequately coincides with echocardiographic data.
      PATIENTS AND METHODS: We studied 23 patients with ischemic heart disease referred
      for clinical 99mTc tetrofosmin Gated SPECT imaging. The results were compared
      with those obtained using a standard rest echocardiographic assessment. Both
      studies were performed within a 24-48 hour period. Segmental results in both
      studies were analyzed by semiquantitative visual scoring using a two or three
      point grading system and a summed score was obtained to determine global left
      ventricular function. RESULTS: There was a good segmental score agreement between
      both techniques for wall motion (77.5%; kappa = 0.49) and less for wall
      thickening (85%; kappa = 0.36). There were non significant statistical
      differences in the global left ventricular function with both techniques by wall
      motion (echocardiography 15.3 +/- 5.4 vs tetrofosmin 14.9 +/- 4.4; p = NS) and
      wall thickening (echocardiography 12.7 +/- 2.3 vs tetrofosmin 12.4 +/- 1.8; p =
      NS) scores. Correlation for global wall motion (r = 0.81; p < 0.0001) and wall
      thickening (r = 0.72; p = 0.0001) scores between the two modalities was good.
      CONCLUSIONS: Gated SPECT 99mTc tetrofosmin myocardial imaging is a valid method
      to assess segmental and global left ventricular function and agrees well with
      echocardiography.

PMID- 9580396
TI  - [Home hospitalization for children with cancer: one more step towards integral
      care in pediatric oncology].

PMID- 9580395
TI  - [Amoxicillin-clavulanic acid hepatotoxicity].

PMID- 9580397
TI  - [A survey on the inclusion criteria in pediatric dialysis and transplantation
      programs in terminal renal failure].
AB  - OBJECTIVE: The purpose of this study was to know the current practices of Spanish
      pediatric nephrologists concerning the inclusion or not of children with end
      stage renal disease (ESRD) in programs of dialysis and transplantation in order
      to open a discussion on the topic that would allow a consensus to be reached.
      PATIENTS AND METHODS: A descriptive and prospective study using an anonymously
      mailed survey to 90 members of the Spanish Pediatric Nephrology Association was
      carried out. RESULTS: The index of response was 43%. In 90% of the physicians
      polled they believe that some situations exist where it is advisable not to
      include a child with ERF in dialysis and, although all assure that there are no
      written procedures, a large majority (85%) think that they should exist, at least
      in the most representative cases. Serious physical and/or intellectual handicap
      and poor prognosis constitute the most important factors for making a decision.
      The expressed desire of the parents is considered the third most important factor
      by 56%. Of the answers, 82% placed economic cost of the substituting treatments
      as least important. Ninety-two percent think that not always and not in all cases
      is it necessary to turn to all possible technical means to extend the life. More
      than half (54%) think that the last decision must be taken by the physician and
      the family, although 44% confer this power to the Ethical Committee. CONCLUSIONS:
      It would be useful to develop guidelines to help pediatric nephrologists and/or
      ethical committees to decide, with the family of the patient, about the inclusion
      of the child in ESRD in programs of dialysis and transplantation.

PMID- 9580399
TI  - [Neonatal morbidity associated with meconial amniotic fluid].
AB  - BACKGROUND: The significance of meconium-stained amniotic fluid (MSAF) is
      discussed, both in regards to obstetric and pediatric management. The primary
      concerns regarding MSAF have been its significance as a sign of fetal
      distress/perinatal asphyxia and the prevention of associated morbidity such as
      meconium aspiration syndrome. The objectives of our study were: (1) To know the
      incidence and type of MSAF, (2) to study the associated morbidity in newborns
      with MSAF admitted to the Neonatal Care Unit (NCU), and (3) to analyze the
      perinatal differences between newborns with moderate versus thick MSAF. PATIENTS
      AND METHODS: A retrospective study was performed to know the incidence of MSAF in
      all of the deliveries in our hospital during a 4 year period. The consistency of
      meconium was classified into 3 classes, thin (light), moderate or thick (heavy).
      On the other hand, a prospective analysis was undertaken to determine the
      morbidity of all meconium-stained neonates admitted to our NCU during this
      period, mainly in relation to perinatal asphyxia, pulmonary, gastrointestinal and
      infectious pathology and neonatal mortality. RESULTS: The presence of MASF
      complicates 18% of all of our deliveries with it being mild in 10.8%, moderate in
      4.4% and severe in 2.8%. Of all newborns with MSAF, one third were admitted to
      the NCU, mainly for two reasons, association with perinatal asphyxia (124 cases)
      and observation of a risk of meconium aspiration syndrome (85 cases). The main
      neonatal morbidities associated with MSAF in our populations were perinatal
      asphyxia in 56.1% (32 cases of severe perinatal asphyxia and 92 non-severe),
      pulmonary pathology in 34% (meconium aspiration syndrome in 32 cases and other
      respiratory abnormalities in 43) and gastrointestinal pathology in 30.5%
      (transitory feeding intolerance in all cases). Four cases of meconium-stained
      neonates were exitus. The neonatal morbidity is significantly more frequent in
      relation to thick meconium and also if perinatal asphyxia is associated to MSAF.
      CONCLUSIONS: Although the relationship between MSAF and perinatal asphyxia is
      controversial, their association increases neonatal morbidity. In accordance with
      our results, thick meconium is implicated as a risk factor influencing the well
      being during the intrapartum and postpartum periods.

PMID- 9580398
TI  - [Facial asymmetry with crying: a neurophysiological study and clinical account of
      this entity].
AB  - OBJECTIVE: The objectives of this study were to determine in our newborn
      population the frequency of facial asymmetry during crying or congenital
      hypoplasia of the depressor anguli oris muscle (DAOM) without associated major
      malformations and to evaluate the contribution of electrophysiological studies in
      the diagnosis of this anomaly. PATIENTS AND METHODS: We performed a prospective
      study of the living newborns with facial asymmetry which did not need to be
      admitted to the hospital and that were delivered without the use of forceps in
      our hospital during 4 consecutive years. Newborn evaluation included physical
      examination, facial nerve electroneurography and DAOM electromyography. RESULTS:
      This anomaly without major malformations was present in 0.348/1,000 newborns.
      Electrophysiological studies demonstrated a normal latency in the facial nerve
      electroneurography and an absence or reduced number of motor unit potential
      without signs of denervation in the electromyography. CONCLUSIONS: Diagnosis of
      this entity is important to exclude facial nerve palsy. Only a physical
      examination is necessary for a correct diagnosis.

PMID- 9580400
TI  - [What is your diagnosis? Pustulous lesions on the face. Tinea faciei].

PMID- 9580401
TI  - [An outbreak of scarlet fever in an urban health center in 1997].

PMID- 9580402
TI  - [Weight loss in an adolescent at social risk].

PMID- 9580403
TI  - [Intermittent claudication: review of a disease of growing prevalence. II.
      Treatment].

PMID- 9580404
TI  - [Carboxyhemoglobin levels and risk factors of carbon monoxide poisoning].

PMID- 9580405
TI  - [Antiphospholipid antibodies in acute infection caused by hepatitis C virus].

PMID- 9580406
TI  - Prevalence of skin reactions to aeroallergens in asthmatics of Puerto Rico.
AB  - In Puerto Rico, although a high prevalence of asthma has been reported, the
      sensitization rates to aeroallergens in these patients is unknown. The purpose of
      this study using a case control design, was to determine and compare the rates of
      sensitization to common aeroallergens in an asthmatic population of 576
      asthmatics and 144 healthy controls. A skin prick test was conducted using
      standardized extracts of Dermatophagoides farinae (Df) and D. pteronyssinus (Dp),
      house dust (HD), cat hair and epithelium (CT), dog hair and dander (DG), grass
      pollen mix (PG), tree pollen mix (PT), weed pollen mix (PW), Aspergillus mix
      (AM), mold mixes A (MA) and B (MB), Periplaneta americana (PA) and Alternaria
      Hormodendrum mix (AH). In addition, an extract from the domestic mite Blomia
      tropicalis (Bt) was also used. A wheal > or = 3 mm2 was considered a positive
      reaction. In addition, a standardized questionnaire was administered and a
      preliminary domestic mite identification survey was conducted. The analysis of
      the data showed that 85.8% of the asthmatics had at least one positive reaction
      and 61.6% of them had positive skin reactions to atleast one mite species.
      Asthmatics reacted to domestic mites 6.19 times more than the control group (p <
      0.0001) and was the largest significant difference found in this study for any
      allergen tested. Preliminary identification of the acarologic fauna in southern
      Puerto Rico demonstrated that Blomia tropicalis, Dermatophagoides pteronyssinus,
      D. farinae and E. maynei are the dominant domestic mite species found in homes of
      asthmatic individuals. These results demonstrate that domestic mites are a very
      important source of sensitizing aeroallergens for asthmatic patients in Puerto
      Rico. Based upon the mite survey, Blomia tropicalis plays an important role in
      allergic sensitization, in addition to Dermatophagoides pteronyssinus and D.
      farinae. The skin prevalence to pollens and to molds may not reflect the true
      prevalence of sensitization to these allergens. Pollen identification and counts,
      and a survey of microflora of Puerto Rico are needed in order to identify and
      validate important allergens that eventually could be incorporated into a more
      appropriate panel for testing sensitization in susceptible individuals.

PMID- 9580407
TI  - Maxillary sinus augmentation using different grafting materials and dental
      implants in monkeys. Part I. Evaluation of anorganic bovine-derived bone matrix.
AB  - The aim of this study was to evaluate clinically, histologically and
      histometrically the use of anorganic bovine bone matrix (i.e. Bio-oss) as a
      grafting material for maxillary sinus augmentation procedures. In 4 adult male
      rhesus monkeys (i.e. Macaca mulatta) the 1st, 2nd and 3rd maxillary molars on one
      side of the jaws were extracted. The remaining bone between the alveolar crest
      and the bottom of the sinus was then reduced to 3-4 mm. After 3 months, maxillary
      sinus augmentation procedures were performed on one side of the jaws in each
      monkey and the sinuses were grafted with the bovine bone matrix. At that time, 2
      IMZ pure titanium plasma coated implants were immediately placed into the
      augmented sinuses (i.e. simultaneous implants-loaded group). After 4 months, 2
      additional similar implants were placed into these previously augmented sinuses
      (i.e. delayed implants-loaded group). Four months later, the abutment connection
      was performed and all 4 implants were loaded with a gold-alloy bridge for 6
      months (i.e. until sacrifice of the animals). The contralateral side of each
      monkey received the same treatment with the exception that the extractions were
      performed 7 months after those in the opposite side and that the implants in this
      side were not loaded. Thus, 2 additional study groups (i.e. simultaneous implants
      unloaded group and delayed implants-unloaded group) were obtained. Clinically,
      all loaded implants were stable at the day of sacrifice. Histologically, the
      grafted sinuses exhibited significant bone formation with integration of the
      bovine bone matrix particles to the new bone. Direct mineralized bone-to-implant
      contact was greater for the delayed implant placement groups than for the
      implants installed simultaneously with the sinus augmentation. Furthermore, the
      percentage of direct mineralized bone-to-implant contact was greater in the
      residual bone than in the augmented area. It was concluded that the anorganic
      bovine bone matrix facilitated bone formation and implant osseointegration in the
      augmented sinuses and that the delayed implant placement in combination with the
      sinus augmentation procedure seemed to be preferable.

PMID- 9580408
TI  - Maxillary sinus augmentation using different grafting materials and
      osseointegrated dental implants in monkeys. Part II. Evaluation of porous
      hydroxyapatite as a grafting material.
AB  - The aim of this study was to evaluate clinically, histologically and
      histometrically the use of porous hydroxyapatite (i.e. Interpore-200) as a bone
      grafting material for maxillary sinus augmentation procedures. In 4 adult male
      rhesus monkeys (i.e. Macaca mulatta) the 1st, 2nd and 3rd maxillary molars on one
      side of the jaws were extracted and the remaining bone between the alveolar crest
      and the bottom of the sinus was reduced to 3-4 mm. After 3 months, maxillary
      sinus augmentation procedures were performed on one side of the jaws in each
      monkey, and the sinuses grafted with the porous hydroxyapatite. Two IMZ titanium
      plasma-sprayed cylinder implants were then immediately placed into the augmented
      sinus (i.e. simultaneous implants-loaded group). After 4 months, 2 additional
      similar implants were placed into the previously augmented sinuses (i.e. delayed
      implants-loaded group). Four months later, the abutment connection was performed
      and all 4 implants were loaded with a gold-alloy bridge for 6 months (i.e. until
      sacrifice). The contralateral side of each monkey received the same treatment
      with the exception that the extractions were performed 7 months after those in
      the opposite side and that the implants in this side were not loaded. Thus, 2
      additional study groups (i.e. simultaneous implants-unloaded group and delayed
      implants-unloaded group) were obtained. Clinically, all loaded implants were
      stable at the day of sacrifice. Histologic analysis demonstrated a significant
      amount of new bone formation in the augmented sinuses. Porous hydroxyapatite
      graft particles appeared to be integrated to the new bone. The percentage of
      direct mineralized bone-to-implant contact in the augmented area was greater on
      the delayed-placed implants than on the simultaneously-placed implants. Also, the
      percentage of direct mineralized bone-to-implant contact was greater in the
      residual bone than in the augmented area. It was concluded that this porous
      hydroxyapatite bone graft enhanced bone formation and bone-to-implant contact in
      the augmented sinuses and that the delayed implant placement in combination with
      the sinus augmentation procedure appears to result in a higher percentage of
      direct mineralized bone-to-implant contact.

PMID- 9580409
TI  - Maxillary sinus augmentation using different grafting materials and dental
      implants in monkeys. Part IV. Evaluation of hydroxyapatite-coated implants.
AB  - The aim of this study was to evaluate clinically, histologically and
      histometrically the use of hydroxyapatite-coated dental implants in conjunction
      with maxillary sinus augmentation procedures. In 4 adult male Rhesus monkeys
      (Macaca mulatta) the 3 maxillary molars on 1 side of the jaws were extracted and
      the remaining bone between the alveolar crest and the floor of the sinus was
      reduced to 3-4 mm. After 3 months, maxillary sinus augmentation procedures were
      performed in each monkey and the sinuses were grafted with a porous
      hydroxyapatite bone graft (Interpore-200). At the same time, 2 hydroxyapatite
      coated cylinder implants (IMZ) were immediately placed into the augmented sinuses
      (i.e. simultaneous-implants-loaded group). Four months later, 2 additional
      similar implants were placed into the previously augmented sinuses (i.e. delayed
      implants-loaded group). After 4 months, the abutment connection was performed and
      all 4 implants were loaded with a gold-alloy bridge for 6 months (i.e. until
      sacrifice of the animals). The contralateral side of each monkey received the
      same treatment with the exception that removal of the maxillary molars was
      performed 7 months after those in the opposite side, and that the implants in
      this side were not loaded. Thus, 2 additional study groups (i.e. simultaneous
      implants-unloaded group and delayed-implants-unloaded group) were obtained.
      Clinically, all loaded and unloaded implants were stable the day of sacrifice.
      Histologically, the grafted sinuses exhibited a significant amount of new bone
      formation with integration of the porous hydroxyapatite graft particles and
      hydroxyapatite-coat of the dental implants to the new bone. Histometric analysis
      indicated that on the loaded side the implants placed simultaneously with the
      sinus lift procedure exhibited greater direct mineralized bone-to-implant contact
      than the delayed placed implants. In addition, the percentage of direct
      mineralized bone-to-implant contact was significantly greater in the residual
      bone in comparison to the augmented area in all groups. Loading of the implants
      exhibited a positive effect on the percentage of direct mineralized bone-to
      implant contact in the augmented area. It could be concluded that hydroxyapatite
      coated implants may be of benefit when used in conjunction with sinus
      augmentation procedures.

PMID- 9580410
TI  - [Impact of zidovudine treatment and the pneumocystis carinii prophylaxis in
      natural history of patients with HIV infection].
AB  - INTRODUCTION: Early use of prophylactic regimens against Pneumocystis carinii and
      zidovudine therapy, may have modified the natural history of patients with HIV-1
      infection. We describe the incidence of opportunistic infections and analize the
      mortality rate in those patients to check the occurrence of any change in the
      above mentioned natural history. PATIENTS: Clinical charts of patients with HIV-1
      infection attending our hospital are reviewed, from november 1987 to june 1994.
      RESULTS: We found 200 patients with AIDS, documenting 64 (32%) deaths and 69
      (34.5%) patients lost to follow-up. Seven HIV-1 infected patients (3.5%) received
      primary prophylaxis against Pneumocystis carinii and 17 (8.5%) zidovudine therapy
      before developing AIDS. Patients with AIDS receiving zidovudine therapy had a
      higher survival (median 50 months) than those not receiving such therapy (median
      17 months; p < 0.001). Ninety one patients with tuberculosis receiving zidovudine
      therapy had also a higher survival than those not receiving antirretroviral
      therapy (p < 0.01). Eighty six patients with Pneumocystis carinii pneumonia
      receiving zidovudine had also a higher survival (p < 0.001). Likewise, patients
      on zidovudine treatment had a lower reduction on CD4 lymphocyte count.
      CONCLUSIONS: The spectrum of AIDS-defining illnesses is similar to the whole
      country. We have not found any difference in the incidence of opportunistic
      infections, but we observed a trend to reduction in the incidence rate of PCP.
      The introduction of zidovudine therapy seems to have a positive influence on the
      survival of AIDS patients. This advantage is highlighted in those patients more
      immunodeficients at first.

PMID- 9580411
TI  - [Emergency department observation and short term unit].
AB  - BACKGROUND: An emergency department observation and short term unit is analyzed,
      and the conditions appropriate for it. METHODS: Four hundred patients admitted
      consecutively were evaluated. Demographic, and clinical data, complementary tests
      performed, diagnosis, destination and revisits to the emergency department were
      analyzed. RESULTS: The 57% of the patients were over 65 years. Complementary
      tests were performed in all patients. 42% were discharged home without
      hospitalization, being syncope, intoxication and epilepsy the most common
      diagnosis. The 1.8% of the patients no hospitalized revisted to emergency
      department during the next 72 hours. CONCLUSION: Emergency department observation
      and short term units can reduce hospitalization and health care costs and improve
      the quality of medical care through extended evaluation and treatment.

PMID- 9580412
TI  - [Most common cardiovascular diseases and sleep apnea syndrome. A general
      population study].
AB  - BACKGROUND: The sleep apnea syndrome (SAS) is a frequent disease associated with
      significant morbidity. The aim of our study was to investigate diseases
      associated with the sleep apnea syndrome (SAS) in general population. METHODS: We
      selected a random sample of 110 people from the electoral census. These people
      were invited to the clinic where medical history, physical examination and
      monitoring for sleep-disordered breathing was done. RESULTS: Twenty two subjects
      were diagnosed of SAS. The prevalence of arterial hypertension in the SAS group
      was 36.4%, and coronary artery disease 13.6%. CONCLUSIONS: Although the
      prevalence of this diseases was increased in the SAS group, we do not see
      significant association with this disease.

PMID- 9580413
TI  - [Drug interactions and their management in patients with human immunodeficiency
      virus infection].
AB  - In fact patients with human immune deficiency virus infection are in treatment
      with multidrugs regimen, also in antiretrovirical therapy as profilaxis and
      treatment opportunist infections and other problems, in other fact the high tase
      of intravenous drugs users in meta-done programming (one of the principal
      transmission cause). Consequently is necessary an rational approximation to this
      problem also in the deepth knowledgment of his mechanisms and his management in
      the daily clinical practice.

PMID- 9580414
TI  - [Paget's disease and sarcomatous degeneration].

PMID- 9580415
TI  - Intra-hippocampal administration of cycloheximide attenuates the restraint
      induced exploratory deficit of an elevated plus maze.
AB  - Rats submitted to 2 h of restraint stress show a reduced open arm exploration in
      the elevated plus maze 24 h later. The stress-induced exploratory deficit is
      prevented by i.c.v. pre-stress administration of cycloheximide (CHX), a protein
      synthesis inhibitor. The objective of the present work was to determine if the
      hippocampus could be involved in this effect. CHX (4 or 8 microg) was injected
      into the dorsal hippocampus of male Wistar rats (200-250 g), immediately before
      (n = 9-20 animals/group) a 2 h period of forced restraint. After 24 h the animals
      were tested in the elevated plus maze. Non-stressed, control groups, received
      saline (SAL) or cycloheximide (CHX, n = 6-12/group) and were tested 1 or 24 h
      later in the maze. Pre-stress microinjections of cycloheximide increased
      exploration of open arms in the elevated plus maze (percentage of entries, SAL =
      10.3 +/- 2.7, CHX 4 microg = 24.5 +/- 4.6, CHX 8 microg = 28.2 +/- 4.8,
      percentage of time spent, SAL = 2.0 +/- 0.6, CHX 4 microg = 8.4 +/- 2.3, CHX 8
      microg = 9.6 +/- 2.6, Duncan test, P < 0.05). No drug effect was observed in non
      stressed animals. These results suggest that blockade of protein synthesis in the
      dorsal hippocampus during the restraint period may attenuate the behavioural
      consequences of stress.

PMID- 9580416
TI  - Effect of seasonal exposure to pollen on nonspecific interleukin-4, interleukin
      5, and interferon-gamma in vitro release by peripheral blood mononuclear cells
      from subjects with pollinosis.
AB  - The immune response to environmental allergens depends on both genetic and
      environmental factors. Allergen exposure triggers the activation of allergen
      specific Th2 cells in allergic patients, as well as increased Th2-type cytokine
      mRNA expression and eosinophil recruitment. Nevertheless, different patterns of
      release of cytokines could explain the heterogeneity of atopic response. In our
      study, 25 patients with pollinosis and 15 healthy donors were selected to
      characterize their release of Th2 (interleukin [IL]-4 and IL-5) and Th1
      (interferon-gamma [IFN-gamma]) cytokines, both during and outside the pollen
      season. Peripheral blood mononuclear cells from patients and controls were
      isolated, cultured in the presence of phorbol-12-myristate-13-acetate plus
      ionomycine, and phytohemagglutinin (PHA), and cytokine release was assessed by
      titration in the supernatants. Both IL-4 and IL-5 showed higher levels during
      than outside the pollen season in pollinic patients (P<0.05) after nonspecific
      stimuli, whereas IFN-gamma levels were significantly lower during than outside
      the pollen season only after culture with PHA. Significant differences were not
      observed in the control group. Our results are consistent with the hypothesis
      that release of cytokines by peripheral blood mononuclear cells from patients
      with pollinosis depends on environmental exposure to sensitizing pollens, and
      that influence can be revealed by in vitro nonspecific stimulation. Nevertheless,
      the heterogeneity in results suggests that the use of mitogens to assess Th1/Th2
      dominance may need careful evaluation.

PMID- 9580417
TI  - Gastric inflammatory myofibroblastic proliferation in children.
AB  - Gastric inflammatory myofibroblastic proliferation (IMP) is an extremely rare
      entity in children, which to our knowledge has only been mentioned in case
      reports. We describe the ninth pediatric case and review the literature
      concerning the etiology, clinical and laboratory features, pathology, treatment,
      and outcome. There has been a predominance in preschool females. Abdominal pain,
      upper gastrointestinal hemorrhage, and an abdominal mass, either isolated or
      associated, have been the main clinical features. Iron-deficiency anemia has been
      a constant finding. Lesions are elevated and involve the full thickness of the
      gastric wall, usually with ulceration of the luminal surface; extragastric
      extension suggesting malignancy is frequent. Diagnosis is made by histology after
      surgical excision. There was no mortality directly related to gastric IMP, and
      only one case recurred after surgical excision. The pathogenesis is
      controversial, but the finding of Helicobacter pylori in our case may indicate an
      inflammatory origin. Awareness of this benign lesion and its mimicry of
      malignancy is important so that inappropriately aggressive therapy can be
      avoided.

PMID- 9580418
TI  - Unexpected late graft failure 9 months after HLA-identical bone marrow transplant
      (BMT) for chronic myeloid leukemia (CML): treatment with a second BMT.
AB  - We describe a patient with CML in 1st chronic phase (CP) who experienced a graft
      failure 9 months after an HLA genotypically identical sibling BMT. Drug toxicity,
      viral infections, chronic graft-versus-host-disease (GVHD) or leukemic relapse
      were excluded. Chimerism study showed 85% of donor marrow cells. She underwent a
      second BMT, reengrafted but died of grade IV acute GVHD.

PMID- 9580419
TI  - Characterization of the acute endocrine actions of (-)-11-hydroxy-delta8
      tetrahydrocannabinol-dimethylheptyl (HU-210), a potent synthetic cannabinoid in
      rats.
AB  - In the present study we have characterized the effects of the acute
      administration of the synthetic cannabinoid (-)-11-hydroxy-delta8
      tetrahydrocannabinol-dimethylheptyl (HU-210, 4, 20 and 100 microg/kg), on the
      secretion of prolactin, growth hormone, luteinizing hormone, follicle-stimulating
      hormone, adrenocorticotropic hormone and corticosterone in adult male rats. HU
      210 administration resulted in a dose-dependent inhibition of plasma growth
      hormone, follicle-stimulating hormone and luteinizing hormone 60 min after the
      acute intraperitoneal injection, starting at 20 microg/kg. Plasma
      adrenocorticotropic hormone and corticosterone levels revealed a dose-dependent
      activation of the pituitary-adrenal axis after acute exposure to HU-210. Plasma
      prolactin levels reflected a biphasic action of HU-210: the 4 microg/kg dose
      resulted in high prolactin levels and the 20 and 100 microg/kg doses induced a
      decrease in the levels of this hormone. The time course of the endocrine effects
      of HU-210 was examined using the 20 microg/kg dose and was found to parallel the
      onset of the immobility and hypothermic effects of this cannabinoid. HU-210 (20
      microg/kg) was also found to block the hormonal surges of luteinizing hormone,
      follicle-stimulating hormone and prolactin occurring during the afternoon of the
      proestrus phase in adult female rats. This dose induced activation of tubero
      infundibular dopaminergic neurons, as reflected by the decrease in hypothalamic
      contents of dopamine in both males and females in the afternoon of the proestrus
      phase. The actions of HU-210 during early postnatal development revealed a
      delayed maturation of the endocrine response to HU-210, with respect to the
      behavioral effects. The findings of the present study reveal that HU-210 induces
      a set of endocrine alterations closely related to those described for natural
      cannabinoids such as delta9-tetrahydrocannabinol but at doses 50-200 times lower
      than those required for delta9-tetrahydrocannabinol.

PMID- 9580420
TI  - Participation in a pharmacological hypolipidaemic trial does not alter
      participants' dietary habits.
AB  - OBJECTIVE: The aim of this study was to observe whether the act of participation
      in a well-controlled clinical trial can, co-incidentally, modify the dyslipaemic
      patient's adherence to his/her diet. DESIGN AND SUBJECT: Food diaries of 55 men
      and 51 women (aged 46.4 +/- 10.6 and 55.8 +/- 12.1 years respectively) were
      analyzed at the beginning and the end of the double-blind stage of treatment (12
      weeks). STATISTICS: Variance analysis and multi-variant analysis with repeated
      data by SPSS/PC statistical package. RESULTS: In neither sex were there any
      statistically significant differences between the start and end of the study with
      respect to the intake of energy, proteins, total lipids, carbohydrates, saturated
      fatty acids, polyunsaturated fatty acids, cholesterol, fibre and alcohol.
      CONCLUSIONS: Although in individual cases some changes in dietary awareness can
      occur, on a larger scale, the hypocholesterolaemic intervention trial induced no
      significant overall changes in the participants dietary/lifestyle patterns and,
      as such, augurs well for other such trials in which the effect of the therapy may
      sometimes be confounded by changes in the patients' life-style patterns
      coincidental to the act of participation in the trial.

PMID- 9580422
TI  - Ixodes ricinus strains in Europe.
AB  - An analysis of cuticular hydrocarbons (CH) of unfed adult Ixodes ricinus ticks
      collected throughout Europe showed that there are 10 distinct I. ricinus groups.
      Studies on the seasonal and annual consistency of CH composition and possible
      effects of host and environmental factors suggested that CHs may be used as a
      genuine genetic marker for I. ricinus. Preliminary studies compared the vector
      competence of ticks from three of the most separated I. ricinus groups and the
      results suggested that there may be significant differences in tick
      susceptibility to Borrelia afzelii.

PMID- 9580421
TI  - Influence of maturation and ageing on the biotransformation of noradrenaline in
      the rat.
AB  - The present investigation was undertaken to study the influence of maturation and
      ageing on the disposition of noradrenaline by the aorta, heart (ventricle), liver
      and kidney of the rat. Slices of these tissues taken from rats aged less than 18
      h, 2.5-3 months or 18-24 months were incubated with 0.1 mumol.l-1 3H-amine during
      30 min. At the end of this period, the accumulation of the intact amine in the
      tissue, as well as the 3H-metabolites formed (3,4-dihydroxyphenylethylglycol, 3,4
      dihydroxymandelic acid, normetanephrine and O-methylated deaminated metabolites)
      were determined by scintillation counting. The results obtained show that in the
      rat: 1) at any age, noradrenaline is preferentially deaminated; 2) while the
      capacity of the sympathetic nerve terminals in accumulating noradrenaline is
      rather well developed at birth, the metabolic system for its degradation is still
      immature; 3) aldehyde dehydrogenase activity or that of its co-factor (or both)
      of the heart is apparently missing at birth; 4) removal of noradrenaline by the
      liver and the kidney did not change with ageing, while that by the aorta
      decreased and that by the heart increased.

PMID- 9580423
TI  - European reservoir hosts of Borrelia burgdorferi sensu lato.
AB  - Existing knowledge on reservoir hosts of Borrelia burgdorferi sensu lato was
      collated and reviewed and several species, particularly birds, were identified as
      reservoir competent. At the present time, 9 small mammals, 7 medium-sized mammals
      and 16 bird species, including passerines, sea birds and pheasants, appear to be
      capable of transmitting spirochaetes to ticks and thus of participating in the
      natural circulation of B. burgdorferi s.l. in Europe. The house mouse, Mus
      musculus is strongly suspected of reservoir competence and many other small
      rodent species, particularly in eastern Europe and Russia, have been implicated.
      Ungulates are not thought to play a major role as reservoir hosts, though co
      feeding transmission may permit some tick infection. The criteria for
      establishment of reservoir status are outlined and a method for identification of
      host blood meals of previous instars of unfed ticks, developed in a participant
      laboratory, is briefly described.

PMID- 9580424
TI  - Lyme borreliosis habitat assessment.
AB  - Tick ecologists throughout Europe provided descriptions of Lyme borreliosis
      habitats according to a standardised format and data for 105 habitats in 16
      countries were received. The data showed that high risk situations, as defined by
      the presence of large numbers of B. burgdorferi sensu lato-infected nymphal I.
      ricinus, occur in heterogeneous deciduous woodland, usually with a recreational
      function and with a diverse fauna, usually including deer. Large numbers of ticks
      occurred in some other habitats, but infection prevalence was usually low. The
      situation for adult I. ricinus was similar but less clearly defined. Tick
      infection rates were found to be lower in western Europe than in the east, and
      the infection rate in I. persulcatus, the most easterly vector species, was
      markedly higher than in I. ricinus. In the vast majority of habitats the
      infection rate in adult I. ricinus was greater than in nymphs. Larvae were rarely
      found to be infected.

PMID- 9580425
TI  - Sporogony and experimental transmission of Babesia equi by Boophilus microplus.
AB  - The development of Babesia equi in salivary glands of adult female Boophilus
      microplus was observed under a light microscope using semithin sections stained
      with toluidine blue. Engorged nymphs were obtained from splenectomized foals
      experimentally infected with B. equi. As adults, they were then fed on rabbits
      for 5 days and the salivary glands of manually collected individuals were removed
      at intervals of 24 h. Sporozoites were found in type III granular acini cells
      between the 2nd and 5th days following feeding on the rabbits. Sporoblasts and
      sporozoites were observed in the same or adjacent acini cells in all the glands
      examined. The formation of the sporozoites occurred following the multiple
      division of the sporoblasts through a process of radial budding from the
      periphery of bodies resulting from multiple fission. Sporozoites were detected in
      smears of adult males stained with Giemsa, between the 2nd and 5th days following
      feeding by the ticks. Adults of B. microplus, fed during the nymphal phase on
      foals with patent parasitemia, transmitted sporozoites of B. equi to a
      splenectomized foal. The role of B. microplus in the transmission and
      epidemiology of B. equi is discussed.

PMID- 9580426
TI  - [Iron deficiency and pica].
AB  - PURPOSE: To study the relationship between pica and iron-lack anaemia in a series
      of iron-deficiency patients in order to establish the pathogenesis of such
      relationship. PATIENTS AND METHODS: Four-hundred and thirty-three patients were
      analysed. Pica was studied by introducing certain diet queries into the clinical
      history. All patients received oral iron and were periodically controlled with
      the usual clinico-haematological procedures. RESULTS: Pica was present in 23
      patients (5.3%). Eight nourishing (namely, coffee grains, almonds, chocolate,
      ice, lettuce, carrots, sunflower seeds and bread) and 2 non-nourishing (clay and
      paper) substances were involved. A second episode of pica appeared in 9 cases
      upon relapsing of iron deficiency. Both anaemia and pica were cured by etiologic
      and substitutive therapy in all instances. No clear correlation was found with
      either socio-economic status or pathogenetic causes of iron deficiency and pica,
      and no haematological differences were seen between patients with pica and those
      without this alteration. CONCLUSIONS: (1) The pathogenesis of pica is unclear,
      although it appears unrelated to the degree of iron deficiency. (2) According to
      the findings in this series, pica seems a consequence of iron deficiency rather
      than its cause. (3) Adequate therapy can cure both conditions, although pica may
      reappear upon relapse of iron deficiency.

PMID- 9580427
TI  - [Acute myeloid leukemia in those over 70 years of age. Experience using low-dose
      ara-C treatment].
AB  - PURPOSE: The treatment of elderly patients with acute myeloid leukaemia (AML)
      remains controversial. We present the results of the treatment of a group of
      patients aged above 70 years with AML diagnosed in our Hospital since 1990.
      PATIENTS AND METHODS: We have studied retrospectively the cases of AML in
      patients older than 70 years diagnosed in our Service since January 1990 to June
      1996. Induction treatment was performed, in all cases but one, with two cycles of
      Ara-C 10 mg/m2/12 h s.c. for 21 days and after haematological recuperation, if
      complete remission had been achieved, monthly maintenance treatment with Ara-C
      (25 mg/m2/12 h oral x 5 days), prednisone (40 mg/m2/day x 5 days) y vincristine
      (1 mg/m2 i.v. x 1 day) was begun. RESULTS: During the period of study 48 patients
      with AML have been diagnosed in our Service, among them 22 (45.8%) were older
      than 70 years. One of them could not be considered for the study as not all data
      from him could be compiled. Among the other 21 patients 5 presented previous
      haematological processes (4 myelodysplastic syndrome and 1 Waldenstrom's
      macroglobulinemia). Initial diagnosis according to FAB classification for AML was
      as follows: 7 M1, 6 M2, 4 M4, 2 M5 and 2 M6. From these 21 patients 2 received no
      treatment due to rapid progression and death, among the other 19, one was
      directly treated with a modification of the maintenance treatment with
      vincristine and prednisone without response (survival 2 months). The other 18
      patients were treated with low-dose Ara-C (described above), among them 3 (16.7%)
      were not evaluable as they did not finish the first cycle of induction treatment;
      8 (44.4%) showed no response; 2 (11.1%) achieved partial remission and 5 (27.8%)
      complete remission. One patient did not show any response after two cycles of low
      dose Ara-C but she obtained complete remission when treated with Ara-C and
      idaurubicin. Overall mean survival was 5.7 months (median 2; 95% confidence
      interval 1.6-9.8 months). In the group of patients treated with low-dose Ara-C
      mean survival was 6.6 months (median 3.5; 95% confidence interval 1.9-11.2
      months). CONCLUSION: We consider that the treatment with low-dose Ara-C is a
      valid option in the treatment of elderly patients (aged 70 or above) with AML
      because 28% complete remissions can be achieved, specially in those ones in which
      other more aggressive treatments are not possible.

PMID- 9580428
TI  - [Posttransfusion graft vs host disease].

PMID- 9580429
TI  - Genital oedema from contact allergy to prednicarbate.

PMID- 9580430
TI  - Transvenous embolization of a dural arteriovenous fistula of the cavernous sinus
      through the contralateral pterygoid plexus.
AB  - We report a new transvenous endovascular route for treatment of dural
      arteriovenous fistulas of the cavernous sinus. The cavernous sinus was approached
      from the contralateral pterygoid plexus and embolization of a dural fistula was
      performed successfully with Guglielmi detachable coils.

PMID- 9580431
TI  - Interleukin-12-dependent activation of human lymphocyte subsets.
AB  - Recently, we reported that IL-12 increased expression and function of CD26/DPPIV,
      this may be a new cellular pathway of the Th1-like immune responses. Here, we
      looked for a specific subset which would respond to CD26 upregulation by IL-12.
      Contrary to previously described results, under our culture conditions (1
      microg/ml of PHA), IL-12 enhanced preferentially the CD8 cell proliferation. By
      using dual fluorescence analysis, IL-12-dependent CD26 expression was found in
      both CD4 and CD8 (previously CD26+ or CD26-) activated T cells and, moreover, the
      CD45RO percentage was unaffected. However, the density of CD45RO Ag (which was
      reported to coexpress with CD26) was impaired. These effects can be implicated in
      the biological functions of IL-12 and provide some clinical possibilities.

PMID- 9580432
TI  - Diagnosis of porcine trichinellosis: parasitological and immunoserological tests
      in pigs from endemic areas of Argentina.
AB  - In order to compare the reliability of serological and parasitological techniques
      for the diagnosis of porcine trichinellosis from endemic areas in Argentina, 116
      pigs were studied: 61 animals from two separate outbreaks and 55 from a small
      abattoir. Direct diagnostic techniques included trichinoscopy and the artificial
      digestion method. Indirect diagnostic tests used in this study were the enzyme
      linked immunosorbent assay (ELISA), employing the excretory-secretory products of
      muscle larvae (ML) as antigen, and the indirect immunofluorescence assay using as
      antigen ML in suspension (IIF-susp), cryostat sections of infected rat muscle or
      of free ML (IIF-slide). The percentage of parasitologically positive pigs was
      invariably lower than that of serologically positive animals (IIF-slide), even
      when digestion studies were carried out individually with a greater amount of
      muscle sample than required by current regulations. Close correlation was found
      between IIF using as antigen tissue sections and IIF using free ML sections,
      while IIF-susp proved unsuitable for diagnosis since this assay presented a high
      percentage of false negative results (20%). The IIF-slide technique proved
      positive in all parasitologically positive animals. ELISA rendered a lower
      percentage of positive reactions than IIF-slide, especially when worm burden was
      low. Since most parasitologically positive animals rendered at least two positive
      serological tests (two variations of IIF or IIF plus ELISA), those negative by
      digestion and positive by two serological methods were strongly suspected of
      having trichinellosis. Upon studying swine from a abattoir it was found that 9%
      of the pigs were positive when assayed by two serological techniques, but
      Trichinella spiralis infection could not be parasitologically confirmed. To sum
      up, serological methods may be used for screening all pigs and positive findings
      should be tested by the digestion method by analysing a greater quantity of pork
      than that required by current regulations, above all in areas with reported
      clinical trichinellosis in humans, to ensure that the pork is safe for human
      consumption.

PMID- 9580433
TI  - Thioperamide, a histamine H3-receptor blocker, facilitates vasopressor response
      to footshocks.
AB  - OBJECTIVE AND DESIGN: We assessed the functional role of the histamine H3
      receptor in conscious intact rats during activation of the sympathoadrenal axis.
      MATERIAL: Male Sprague-Dawley rats, with or without cerebroventricular cannula,
      were subjected to mild footshocks and mean arterial pressure (MAP) and heart rate
      were determined using a tail-cuff plethysmograph. TREATMENTS: Saline,
      phentolamine (3 mg/kg, i.p.), (R)-alphafluoromethylhistidine (AFMH) (100 mg/kg,
      i.p., or 100 microg/5 microl, i.v.t.), (R)-alphamethylhistamine (AMH) (2 mg/kg,
      i.p. or 100 microg/5 microl, i.v.t.), thioperamide (THIO) (1 or 2 mg/kg, i.p., or
      100 microg/5 microl, i.v.t.), mepyramine (10 mg/kg, i.p.), cimetidine (2 mg/kg,
      i.p.). METHODS: Urinary catecholamines were determined by fluorometry.
      Statistical differences between experimental groups were evaluated by Student's t
      test or one-way ANOVA. RESULTS: Footshocks increased both MAP and heart rate. The
      vasopressor response to footshocks was facilitated (p < 0.001) by i.p.
      administration of AFMH, a histidine decarboxylase inhibitor, or THIO, a H3
      receptor antagonist, but not by i.v.t. injection of these drugs. AMH, a H3
      receptor agonist, given i.p., decreased the vasopressor response to footshocks (p
      < 0.001). This action of AMH was abolished by THIO but not by mepyramine or
      cimetidine. The MAP response to exogenous norepinephrine was not altered by i.p.
      administration of either AFMH or THIO. CONCLUSIONS: Our results demonstrate an
      involvement of peripheral histamine H3 prejunctional receptors in the inhibitory
      modulation of peripheral noradrenergic responses during stress.

PMID- 9580434
TI  - Hilar biliary cysts in hepatic transplantation. Report of three symptomatic cases
      and occurrence in resected liver grafts.
AB  - Hilar cysts are infrequent post-transplant biliary tract complications. Thirteen
      cases were discovered among 493 consecutive liver transplants (2.6%). Three
      (0.60%) were symptomatic (obstructive jaundice) while the other ten were found by
      systematically searching in the hilum in a series of 129 consecutive, resected
      grafts at retransplantation or autopsy (n = 54). Two types of cysts were
      detected: in eight grafts (1.6%), these were blind unilocular cavities with
      viscid mucous content, located adjacent to the biliary tract anastomoses. These
      had been inadvertently created as a result of the sequestered remnant cystic duct
      after cholecystectomies and biliary tract reconstructions, where a double
      barreled common duct and long cystic duct had been present in the donor liver.
      These mucoceles ranged from 0.5 to 5.5 cm in diameter (median 1.7 cm). The three
      symptomatic cases were diagnosed by imaging techniques 3.5 years after
      transplantation; however, this type of cyst was found as early as the 2nd month
      post-transplantation when detected in lost liver grafts. Five livers (1%), lost
      between 5 months and 2.8 years post-transplantation, showed cystically dilated
      peribiliary glands, sometimes with multilocular, and occasionally multiple,
      cavities ranging from 0.5 to 2 cm in diameter (median 0.8 cm). This type of cyst
      was asymptomatic and located adjacent to the left, right, or common hepatic
      ducts. Threads were found near four cysts, suggesting that surgical injury may
      have been responsible for obstructing the neck of the glands. With the increasing
      number of long-term survivors of liver transplantation, unless preventive
      surgical methods are implemented, the number of symptomatic cysts of these
      origins can be expected to grow. Transplantation teams should, therefore, be
      aware of these potential causes of biliary tract complications.

PMID- 9580436
TI  - Apoptosis in the human inner ear. Detection by in situ end-labeling of fragmented
      DNA and correlation with other markers.
AB  - The aim of this study was to obtain baseline data on the recently described
      special form of single cell death, apoptosis, in normal human inner ears. For
      this purpose, in situ end-labeling of the fragmented DNA was applied, in
      conjunction with apoptosis-related markers, to detect cellular elements showing
      programmed cell death in decalcified and paraffin-embedded tissues. Over 20
      specimens were analyzed which were obtained from autopsy cases with no history of
      acoustic lesions confirmed by histopathology. Based on staining results, we saw
      no apoptotic signs in the majority of normal adult inner ears. An apoptotic cell
      captured in the Reissner's membrane of the cochlea from an old patient may,
      however, indicate an age-related subtle cell loss with the process of apoptosis.
      Nevertheless, the fact that more apoptosis was not found in our cases suggests
      that this phenomenon does not contribute significantly to the tissue homeostasis
      in the adult inner ear under normal conditions. These data are in accordance with
      our immunohistochemical findings on the p53 nucleoprotein, and proliferating cell
      nuclear antigen expression since there was no staining in any of the cellular
      elements, including the mesenchymal cells. This reflects a stationary and stable
      condition of cells of the vestibular and the cochlear structures, probably to
      maintain their integrity and the fine sensory functions. As opposed to the above
      findings, during inner ear development, the epithelial cells lining the cochlear
      lumen, the ossifying cartilage of the temporal bone, and the mesenchymal cells
      show different degrees of proliferation in combination with single cell death as
      signs of maturation of the vestibular and the cochlear apparatus. In addition,
      apoptosis has been demonstrated in cells of the cochlear stria vascularis from an
      adult patient treated with high doses of cisplatin, vinblastine and bleomycin
      prior to death. Furthermore, a wide range of apoptosis could be induced
      experimentally in a normal ear by an external perfusion of actinomycin D (ActD),
      which is known to produce programmed cell death in many cell types of different
      origins. The potential role of cytostatic agents in the apoptotic process of the
      inner ear needs, however, to be confirmed in large-scale specimens from patients
      treated with genotoxins. The fact, however, that apoptotic cells are also seen in
      association with ActD indicates that the fine sensory structure of the cochlea
      may also be a target for certain chemotherapeutic agents when administered in
      high doses.

PMID- 9580435
TI  - The pharmacology and kinetics of ecto-nucleotidases in the perilymphatic
      compartment of the guinea-pig cochlea.
AB  - This study investigated the characteristics of ecto-nucleotidases in tissues
      lining the perilymphatic cavity of the cochlea. The perilymphatic space of the
      isolated guinea-pig cochlea was maintained with oxygenated artificial perilymph
      (AP) perfused at a rate of 100 microl/min. Following AP perfusion, either
      adenosine triphosphate (ATP), adenosine diphosphate (ADP) or adenosine
      monophosphate (AMP) was introduced into scala tympani, and perfusion arrested for
      2 min for substrate incubation with cochlear tissues. Effluent collected from the
      cochlea was assayed for adenine nucleotide metabolites by reverse-phase high
      performance liquid chromatography (RP-HPLC). Extracellular ATP and ADP were
      rapidly and sequentially hydrolysed to adenosine by Ca2+/Mg2+-dependent and
      Ca2+/Mg2+-independent enzymatic mechanisms. The degradation of extracellular ATP,
      ADP and AMP occurred in the presence of intact tissues, as demonstrated by the
      limited lactate dehydrogenase (LDH) activity (0-2.2%). ATPase activity was not
      affected by inhibitors of intracellular ATPases (oligomycin, ouabain, N
      ethylmaleimide, 100 microM NaN3) and non-specific alkaline phosphatase (beta
      glycerophosphate). The hydrolysis of ATP was inhibited by 5 mM NaN3, suramin,
      ATPgammaS, La3+ and CTP, the hydrolysis of ADP by beta,gamma-imidoATP, and AMP
      degradation by alpha,beta-methyleneADP. Ecto-ATPase, ecto-ADPase and ecto-5'
      nucleotidase followed Michaelis-Menten hyperbolic kinetics, with estimated Km
      values of 2282 microM, 6619 microM and 881 microM, respectively. Our results
      indicate the presence of considerable ecto-nucleotidase activity within scala
      tympani of the cochlea, and support its role as the terminating mechanism for P2
      receptor signalling known to occur in the cochlea. A competition plot is
      consistent with ATP and ADP degradation mediated by the same enzyme (ecto-ADP
      diphosphohydrolase) with two different catalytic sites.

PMID- 9580437
TI  - Liver cirrhosis and mortality by abdominal surgery. A study of risk factors.
AB  - AIM: To determine the mortality-related factors in cirrhotic patients who
      underwent nonderivative abdominal surgery. PATIENTS AND METHODS: We
      retrospectively reviewed the clinical charts of 63 patients (38 men, 25 women)
      with liver cirrhosis and abdominal surgery. Patients who underwent surgical
      derivative procedures for portal hypertension and/or hepatic resection for
      hepatic tumor were excluded. The study population was divided in patients who
      died (Group 1) and alive patients (Group 2). Thirteen (21%) patients died and the
      other 50 (79%) had an uneventful course. We compared the clinical and analytical
      parameters between both groups. Multivariate analysis was performed for the
      variables with predictive value. RESULTS: Prothrombin time and the presence of
      hepatic encefalopathy showed statistical significance in the univariate analysis
      (p < 0.05 and p < 0.01, respectively). However, in multiple logistic regression
      analysis serum bilirrubine value was associated with mortality rate (Odds ratio
      1.65, 95% CI, 0.97-1.14; p = 0.064). Emergency surgery was required more
      frequently in patients of group 1 than in those of group 2, but the difference
      did not achieve statistical significance. CONCLUSIONS: In the present study, the
      serum bilirrubine value, the prothrombin time and the presence of hepatic
      encefalopathy were associated with mortality of cirrhotic patients who underwent
      non-derivative abdominal surgery. The lack of significance of other factors
      (albumin, nutrition, infections and urgent surgery) could be due to the small
      number of patients in our series.

PMID- 9580439
TI  - [Anisakiasis at the ileal level].
AB  - Two cases of ileal anisakiasis are presented here. Symptoms were compatible with
      appendicitis. Either of them were operated on, the both were found and ileal
      tumour. Damage zone was removed. Pathological examination of piece showed us
      anisakis simplex larva set in the mucosa. The evolution of patients had no
      complications, currently they are asymptomatic. Both of them had eaten uncooked
      anchovy some days before. Anisakiasis cases are quite strange in Spain. There was
      only seven cases of anisakiasis in Spanish literature previously.

PMID- 9580438
TI  - [NF-kappa B and inflammatory intestinal diseases].
AB  - The chronic inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and
      ulcerative colitis (UC), are multifactorial pathologies. There is overwhelming
      evidence that genetic factors play a pivotal role in the predisposition to suffer
      from IBD. The severity of the inflammatory response depends on genes coding for
      proteins which regulate the cytokine production. Among them, NF kappa B stands
      out as the most important regulator of the gene expression of several pro- and
      anti-inflammatory genes. We present hereby its structure, function, regulation
      and the role played in IBD. Different theories relating the mechanism of action
      of glucocorticosteroids to NF kappa B are described in this review as well. The
      more accurate knowledge of the NF kappa B physiology has allowed new
      therapeutical approaches to inflammatory diseases to appear, namely the transfer
      to primary intestinal epithelial cells by an adenoviral vector of a mutant I
      kappa B (the inhibitory protein of NF kappa B) and the local use of p65 antisense
      phosphorothioate oligonucleotides.

PMID- 9580440
TI  - [Fulminant hemorrhagic colitis from cytomegalovirus].

PMID- 9580441
TI  - [The clinical utility of the quotient of lipase-amylase and polymorphonuclear
      elastase in acute pancreatitis].

PMID- 9580442
TI  - [Demand for neuropediatric care in a regional general hospital. V. Complementary
      tests].
AB  - INTRODUCTION: Complementary tests orientated by the clinical findings and
      correctly interpreted, are useful in some cases in order to exclude certain
      pathologies and on other occasions to help to orientate towards or to confirm
      diagnoses. Material and methods. In this paper we analyze the complementary tests
      most often used in children evaluated during a five year period, from May 1990 to
      May 1995, by a neuropaediatrician who recently joined the staff of the Hospital
      Miquel Servet in Zaragoza (which had no neuropaediatrician before then). RESULTS
      AND CONCLUSIONS: Neuroimaging is the technique which was most often useful in
      establishing the diagnosis. CT or MR orientated or established the diagnosis in
      21% of the total number of children evaluated and in 39% of the children in whom
      this investigation was carried out. The EEG contributed to the diagnosis of
      epilepsy in 11% of the children. In 16% of the cases of epilepsy the EEG was
      normal or with nonspecific changes and diagnosis was made on clinical grounds
      alone. Biochemical tests enabled some pathologies to be ruled out, but
      contributed to diagnosis on few occasions, most frequently the CSF (basically in
      meningitis and encephalitis) and muscle enzyme tests were also useful. Routinely
      used investigations such as those involving amino acids, ammonia, lactate and
      pyruvate established the diagnosis in a smaller proportion of cases than those
      used more selectively. Genetics were not found to be very useful in diagnosis.
      Reallocation of resources is necessary to permit the population as a whole to
      benefit from the continuous advances being made in techniques of direct study of
      molecular genetics.

PMID- 9580443
TI  - [Post-traumatic epilepsy].
AB  - Post-traumatic epilepsy is a well-known complication of head injury (TCE). There
      is extensive bibliography on the subject which contains contradictory data and
      unanswered questions. In this paper, we review and update the literature
      emphasizing particularly current definitions, incidence, risk factors and
      evaluation of prophylactic treatment in relation to the physio-pathology. We give
      data of a retrospective study of the cases observed during the past 15 years in
      our unit, analyzing the factors which may help to predict the evolution of these
      crises. There is a relationship between the incidence of post-traumatic epilepsy
      and the severity of injury. One of the main risk factors is the presence of focal
      lesions, particularly haemorrhagic lesions. Prophyllactic treatment with anti
      epileptic drugs is only effective during the first week in the group at risk of
      developing early crises. It has not been shown to be of use in preventing post
      traumatic epilepsy. Other treatments, such as antioxidants, calcium antagonist
      and glutamate inhibitors are still only at an experimental stage.

PMID- 9580444
TI  - [Diagnostic focus on the child with focal seizures].
AB  - The diagnostic possibilities applicable in the focal epilepsies of the childhood
      are reviewed, as well as the methods diagnoses to arrive to their determination.
      Stress is made in that it is necessary to keep in more mind the atypical of the
      seizures that the present anomalies or not in the electroencephalogram.

PMID- 9580445
TI  - Massive haemoptysis complicating exogenous lipid pneumonia.
AB  - Exogenous lipid pneumonia is an uncommon condition resulting from the aspiration
      or inhalation of fat or oil material. The prognosis in this entity is usually
      good and complications are rare. We report an unusual case of chronic lipid
      pneumonia complicated with massive haemoptysis who responded to steroid therapy
      after arterial embolization.

PMID- 9580447
TI  - Trigeminal and olfactory sensitivity: comparison of modalities and methods of
      measurement.
AB  - OBJECTIVE: The principal objective was to chart sensitivity for human nasal
      irritation by alternative psychophysical methods, namely, a common detection
      procedure versus a nasal lateralization procedure that required the subject to
      indicate whether a vapor had stimulated the left or right nostril. This objective
      relates to the broader issues as to (a) whether subjects with normal olfaction
      (normosmics) can yield, through novel methodology, an index of sensitivity to
      nasal irritation comparable with that obtained from subjects without olfaction
      (anosmics) and (b) whether both types of subjects have similar irritation
      sensitivity in general. This study sought to gauge interconvertability both
      between types of subjects and between modes of stimulus presentation for
      irritative and, where appropriate, olfactory stimulation. METHODS: Static
      dilution series of four n-aliphatic alcohols, chosen to represent volatile
      organic compounds (VOCs), provided the source of calibrated olfactory and
      irritative vapors emitted from their squeezable containers into the nose or eye
      either by a mechanical device or by hand. Standard psychophysical methodology
      (forced-choice; ascending strength of stimulation) served to chart detection
      thresholds for irritation and odor and an analogous procedure served to chart the
      threshold for localization of stimulation. RESULTS: Within the limits of
      resolution, detection thresholds and nasal localization thresholds yielded
      comparable indices of the potency of the VOCs to evoke nasal irritation. The
      thresholds agreed well with those for detection of eye irritation, though only
      the eyes proved to be capable of detecting irritation from l-octanol. The method
      of emitting the stimulus had little material effect on measures of either
      irritative or olfactory detection. CONCLUSIONS: The threshold for nasal
      localization offers a suitable way to measure nasal irritation in normosmic
      persons. Olfactory stimulation does not interfere with the measure since subjects
      cannot localize on that basis. Anosmic and normosmic persons have comparable
      sensitivity to nasal and ocular irritation. If anosmic persons have any lower
      sensitivity, as sometimes claimed, it would seem to have only trivial
      consequences for estimates of the irritative potency of VOCs.

PMID- 9580446
TI  - Lactic acid fermentation and storage of blanched garlic.
AB  - The controlled fermentation of peeled, blanched garlic, using a starter culture
      of Lactobacillus plantarum, was studied and compared with that of unblanched
      garlic. Blanching was carried out in hot water (90 degrees C) for 15 min. The
      starter grew abundantly in the case of blanched garlic, producing mainly lactic
      acid and reaching a pH of 3.8 after 7 days, but its growth was inhibited in
      unblanched garlic. Ethanol and fructose, coming from enzymatic activities of the
      garlic, and a green pigment were formed during the fermentation of unblanched
      garlic, but not of blanched garlic. The blanched garlic fermented by L.
      plantarum, even without a preservation treatment (pasteurization), was
      microbiologically stable during storage at 30 degrees C in an acidified brine
      (approximately 3% (w/w) NaCl and pH 3.5 at equilibrium), but fructans were
      hydrolyzed. The packed fermented product and that obtained by direct packing
      without fermentation were not significantly different with regard to flavour.

PMID- 9580448
TI  - Oral metamizol (1 g and 2 g) versus ibuprofen and placebo in the treatment of
      lower third molar surgery pain: randomised double-blind multi-centre study.
      Cooperative Study Group.
AB  - OBJECTIVE: To assess the efficacy of metamizol 1 g and 2 g in the relief of pain
      after surgical extraction of the lower third molar, and to compare the
      therapeutic effect with that of ibuprofen 600 mg or placebo. METHODS: A total of
      253 patients aged between 18 years and 60 years who had undergone extraction of
      the lower third molar (types II-IV) under local anaesthesia, up to a maximum of
      108 mg of mepivacaine, were randomly assigned to a single oral dose of a new
      galenic form (drinkable vials) of metamizol 1 g (n = 75), metamizol 2 g (n = 72),
      ibuprofen 600 mg (n = 74) or placebo (n = 32). Pain intensity was evaluated by a
      100-mm visual analogue scale. To enter the study, a pain level of 50 mm or more
      was required. The duration of the trial was 1 h. Assessments were carried out at
      15, 30 and 60 min after treatment. RESULTS: The analgesic efficacy of metamizol 2
      g was significantly better than ibuprofen and placebo with regard to all
      evaluated parameters. The values of the pain intensity difference at 15 min, the
      percentage of patients with a decrease of 50% or more on the visual analogue
      scale at 60 min and the sum of pain intensity differences at 60 min showed
      metamizol 2 g to be significantly more effective than metamizol 1 g. In general,
      metamizol 1 g was as effective as ibuprofen 600 mg. The analgesic efficacy of
      placebo was significantly lower than that of all active treatments. A lower
      number of patients treated with metamizol 1 g (n = 1) or metamizol 2 g (n = 1)
      needed rescue medication than those given ibuprofen (n = 7) or placebo (n = 5).
      No serious adverse effects developed and none of the patients had to leave the
      study for this reason. CONCLUSIONS: The model of the lower third molar, for which
      the analgesic outcome referred to the first hour after drug administration,
      demonstrated that the analgesic efficacy of oral metamizol 2 g was significantly
      higher than that of ibuprofen 600 mg or placebo. Metamizol 1 g and ibuprofen 600
      mg showed a similar therapeutic effect. All regimens were as well tolerated as
      placebo.

PMID- 9580449
TI  - Lack of benefit of protease inhibitors on HCV viremia in HIV-infected patients.

PMID- 9580450
TI  - [Serum concentrations of vitamins A, E and ascorbic acid in premenopausal and
      postmenopausal women with breast cancer].

PMID- 9580452
TI  - [Community-acquired bacteremias of urinary origin].

PMID- 9580451
TI  - The use of molecular modelling in the understanding of configurational
      specificity (R or S) in asymmetric reactions catalyzed by Saccharomyces
      cerevisiae or isolated dehydrogenases.
AB  - This method gives a general ideal how to use crystallographic information of
      enzymes to understand reactions catalyzed by these biocatalysts, commonly used by
      biochemists to produce chiral products. The interactions of three acetoacetic
      esters with the enzymes L-lactate dehydrogenase and alcohol dehydrogenase were
      studied through molecular modelling computer program. These artificial substrates
      have been widely used to produce chiral synthons. Through this methodology it was
      possible to understand the conformational specificity of these enzymes with
      respect to the products and how these enzymes can be inhibited by modifying the
      structures of the artificial substrates. Also, it was possible to predict whether
      some type of artificial substrate will suffer reduction by cells that contain
      these dehydrogenases and what kind of configuration (R or S) the final product
      will have.

PMID- 9580453
TI  - [Nosocomial bacteremias of urinary origin].

PMID- 9580454
TI  - [Bacteremia in diabetic patients].

PMID- 9580455
TI  - Occipitocervical fixation with a single occipital clamp using inverted hooks.
AB  - A simple occipitocervical osteosynthesis technique using cervical CCD (compact
      Cotrel-Dubousset) material is described in a clinical case. The originality of
      this technique consists in the occipital fastening used, involving the
      simultaneous insertion of two hooks into a single burr-hole. This greatly
      facilitated the positioning of the osteosynthesis rods, reduced surgical time,
      and provided immediate stability. These criteria are of considerable importance
      since this difficult surgical procedure is often performed in patients in a frail
      condition.

PMID- 9580456
TI  - Red blood cell phenotypes in alpha-thalassemias in the Spanish population.
AB  - BACKGROUND AND OBJECTIVE: alpha-thalassemia is very common on all thalassemic
      geographical regions. The present work aimed at analyzing the relationship
      between the degree of microcytosis and hematological parameters and the type of
      alpha-thalassemic mutation. DESIGN AND METHODS: Five hundred and thirty-six
      subjects with 4 kinds of alpha-thalassemia were examined using established
      techniques that determined all hematological parameters, and globin synthesis and
      molecular biological techniques to study the DNA of globin genes by Southern
      blotting. RESULTS: Adult carriers of alpha (+)-thalassemia (-alpha/alpha alpha)
      present very few hematological alterations. In a statistical comparison with
      normal individuals (alpha alpha/alpha alpha), significant differences were found
      between the hemocytometric data and the MCV and MCH of heterozygous alpha +
      thalassemia and the heterozygous alpha zero or homozygous alpha + genotype. Hb H
      disease was detected in 15 patients, presenting a severe degree of anemia, a
      significant increase in RDW and globin chain synthesis with an alpha/beta ratio
      of 0.5 +/- 0.1. INTERPRETATION AND CONCLUSIONS: These data provide reference
      values for geographical areas where alpha + thalassemia is common. These
      hematocytometric data, together with hemoglobin analysis, could be useful as a
      future reference data for new patients diagnosed with alpha-thalassemia.

PMID- 9580457
TI  - Fractures of allografts used in limb preserving operations.
AB  - One hundred and thirty-seven allografts used since 1986 in limb preserving
      operations for malignant bone tumours were reviewed. The follow up was longer
      than two years. There were fourteen fractures (10.2%) in twelve patients at a
      mean time of 22 months from the operation. Most of them were in the metaphyseal
      area and were related to perforations of the allograft made for stabilisation
      with plates, for tendon and ligament reattachment, or any other hole in the
      allograft. Fractures occurred always after the allograft-host junction was
      united. Healing was achieved in 7 cases by internal fixation with autologous bone
      grafting in a mean of 5 months. In cases of multiple fractures of the allograft,
      the graft was exchanged. We recommend using intramedullary fixation in order to
      reduce the incidence of allograft fracture, and the use of internal fixation,
      with intramedullary whenever possible, and autologous bone grafting to achieve
      consolidation of the fractures.

PMID- 9580458
TI  - [Psychological profile of anesthesia residents in the province of Andalucia].
AB  - OBJECTIVES: To describe the personality traits and value systems of the
      population of residents in anesthesiology of a province in Andalusia and to
      analyze what the ideal profile of an anesthesiologist in training would be.
      SUBJECTS AND METHOD: Forty-four residents in anesthesiology were invited to
      participate, of whom 22 accepted. The participants voluntarily completed
      anonymous written questionnaires with 232 items: the sixteen personality factors
      questionnaire, form A (R.B. Cattell), and the survey of interpersonal values
      (L.V. Gordon). RESULTS: The residents scored high on primary factors of
      intelligence (B), self-sufficiency (Q2) and conservatism (Q1). High scores were
      also recorded on the secondary factors of anxiety (QI) and socialization (QIII);
      low scores were seen for independence (QIV). Four theoretical personality models
      (alpha, beta, gamma and delta) were established based on the data. Four residents
      were alphas (18%), 10 were betas (45%), 6 were gammas (27%) and 2 were deltas
      (10%). CONCLUSIONS: An ideal personal profile for residents in anesthesiology by
      American authors has been available since the 1960s. An ideal resident should be
      independent, calm, aware, stable, secure, self-disciplined and alert; moreover,
      he or she should enjoy team work. The residents with alpha personalities were
      ideal. At present, the training of residents and the selection criteria for
      access to specialized training based on a personality test are scarcely valued in
      our discipline.

PMID- 9580459
TI  - [Pharmacology of spinal facilitation: the basis for preventive analgesia].
AB  - Repeated C fiber stimulation results in increased spinal afferent processing
      leading to exaggerated response to a painful stimulus (hyperalgesia) and
      anomalous pain behavior in response to an otherwise innocuous stimulus
      (allodynia). Evidence points to a complex scenario in which continued C fiber
      stimulation leads to local spinal release of glutamate, which activates spinal N
      methyl-D-aspartate receptors. Their activation then leads to increased
      intracellular Ca and later to spinal formation of several intermediaries,
      including prostanoids and nitric oxide. Both serve to facilitate spinal
      processing directly, by increasing the release of spinal neurotransmitters.
      Conversely, spinal delivery of antagonists of such processes prevents a
      hyperalgesixc state from developing. These observations are clearly relevant to
      the study and management of pain following injury in humans.

PMID- 9580460
TI  - [Anesthesiologic implications of moyamoya disease].
AB  - A 34-year-old woman 22 weeks pregnant suffered cerebral hemorrhage, requiring
      admission to the intensive care unit and mechanical ventilation. She recovered
      without sequelae. The diagnosis was moyamoya disease and she was scheduled for
      elective cesarean delivery at 38 weeks of gestation. After appropriate
      preoperative study and complementary testing (echocardiogram, computerized axial
      tomography of the brain and determination of anti-cardiolipin and other
      antibodies, which were normal) the patient was given intradural anesthesia with
      15 mg of 0.5% bupivacaine and 24 micrograms of fentanyl, with continuous
      monitoring of blood pressure, tympanic temperature and neurological variables.
      Warm intravenous fluids and ephedrine (100 to 250 micrograms/min) were perfused.
      No noteworthy neurological events or hemodynamic changes occurred during or after
      surgery. Postoperative analgesia was provided with 2 mg/12 h of morphine through
      an epidural catheter.

PMID- 9580462
TI  - [Renal adenocarcinoma with vena cava invasion: current status of its diagnosis
      and treatment using total segmentary cavectomy].
AB  - OBJECTIVES: Renal adenocarcinoma is characterized by marked venotropism; 20-49%
      show extension into the main renal vein and 4-19% into the vena cava. The present
      study analyzes the different diagnostic methods to evaluate the vascular
      involvement by renal carcinoma and presents the results achieved by total
      segmental cavectomy with ligation of the left renal vein and without vena caval
      reanastomosis. METHODS: Three patients (two males, one female) underwent total
      segmental cavectomy with ligation of the left renal vein in our Service over the
      last 10 years. A bilateral subcostal approach with access to the large vessels
      was utilized in all three cases. The superior and inferior renal vena cava were
      exposed and the hepatic veins were ligated at the level of the intrahepatic
      segment. Incision of the vena cava was performed, the thrombus was removed and
      the renal vessels were ligated. The proximal and distal segments of the vena cava
      were ligated after cavectomy. In the third patient, intrahepatic extension of the
      thrombus required the use of a temporary filter for the proximal segment of the
      vena cava. RESULTS: The early postoperative course was satisfactory; adequate
      renal function was maintained and no problems with venous return were observed.
      Of the diagnostic methods analyzed, MRI was found to be the most useful. A
      relationship was found between survival and the pathological stage and the
      presence or absence of lymph node metastasis. CONCLUSIONS: Total segmental
      cavectomy without reanastomosis and with ligation of the left renal vein appears
      to be a feasible technique which achieves good results. MRI is the diagnostic
      method of choice in the evaluation of vascular tumor extension.

PMID- 9580461
TI  - The value of cell cultures for the diagnosis of mixed
      myelodysplastic/myeloproliferative disorders.
AB  - BACKGROUND AND OBJECTIVE: Myelodysplastic syndromes (MDS) are a group of
      disorders characterized by dyshematopolesis in bone marrow (BM) and peripheral
      blood (PB) cytopenias. In recent years particular attention has been paid to
      myeloproliferative disorders with dysplastic features or myelodysplastic
      syndromes that evolve into a myeloproliferative disorder. The present study was
      designed to analyze patients with MDS but with a normal or increased colony
      forming capacity, in order to see whether or not cell cultures could contribute
      to the diagnosis of intermediate MDS-MPD conditions. DESIGN AND METHODS: A total
      of 80 patients diagnosed as having MDS were included in the study. CFU-GM assay
      was performed by plating 1 x 10(5) mononuclear cells/mL in IMDM and 0.9% methyl
      cellulose containing 10% PHA-LCM. In all cases cultures were run in parallel
      without PHA-LCM to assess autonomous growth. Cultures were incubated at 37
      degrees C in a fully humidified atmosphere with 5% CO2 and scored at day 14.
      Cytogenetic analysis was performed according to standard procedures. Short-term
      cultures of 24 and/or 48 hours were used. RESULTS: Twenty-two patients out of the
      80 MDS cases included in the study showed a normal or increased cell growth
      pattern. Among these 22 patients, eight were diagnosed as suffering from chronic
      myelomonocytic leukemia (CMML) according to the FAB criteria and were excluded
      from the present analysis. The remaining 14 cases, which constitute the body of
      this study, displayed an increased number of clusters and/or colonies, with an
      altered cluster/colony ratio (anomalous growth) in 10 cases. Autonomous colony
      formation was present in five of these 14 cases and autonomous cluster growth was
      seen in all but three of them. In addition, one patient showed endogenous BFU-E
      growth. Morphological diagnoses were then revised due to this aberrant colony
      growth pattern: based on actual criteria, 3 patients could have been considered
      as having a-CML (atypical chronic myeloid leukemia). Another 6 cases evolved to a
      more proliferative disorder: 5 to CMML, and one to a-CML. Interestingly, in 3 of
      these 6 patients the evolution took place concomitantly with an infectious
      episode. In one additional patient the platelet count increased up to 1000 x
      10(9)/L and required treatment with hydroxyurea. INTERPRETATION AND CONCLUSIONS:
      Our results show that intermediate MDS-MPD cases are relatively common and that
      in vitro characteristics, i.e. high clonogenic capacity with a high
      cluster/colony ratio and scanty autonomous growth, in patients showing
      myelodysplastic features could contribute to an early diagnosis in these cases.
      It is possible that in some cases an infectious episode, through higher cytokine
      secretion, contributes to the development of these disorders.

PMID- 9580463
TI  - [Testicular microlithiasis: diagnosis associated with orchialgia].
AB  - OBJECTIVES: To analyze the possible association between orchidalgia and
      testicular microlithiasis and to determine if this condition has a negative
      effect on fertility. METHODS: Two male patients with similar findings of
      microlithiasis on the testicular ultrasound were studied. One patient had a
      history of thalassemia and the other patient had intermittent episodes of
      testicular torsion. A histological study was performed in both patients. RESULTS:
      The testicular pain remitted spontaneously in the first case and after
      orchidopexy in the other patient. Biopsy disclosed a diminished spermatogenesis
      and no anomaly, respectively. CONCLUSION: Our findings and the reports published
      in the literature indicate that testicular microlithiasis cannot be considered to
      be an etiological factor in orchidalgia or infertility.

PMID- 9580465
TI  - [Application of the polymerase chain reaction to an experimental model of
      infection by herpes simplex virus type 1].
AB  - Herpes simplex type 1 (HSV-1) has been implicated as a cause of facial paralysis.
      We developed an experimental model in rabbits in which we injected HSV-1 into the
      tongue. The animals were killed after one and three weeks. The geniculate and
      trigeminal ganglia and medulla were extracted and the samples were processed. The
      polymerase chain reaction (PCR), nested-PCR and cultures were carried out in
      order to detect the viral genome in the samples. The viral genome was found in
      all but two rabbits. None of the animals developed clinical facial palsy. We
      conclude that nested PCR is more sensitive for the identification of HSV-1 in
      samples.

PMID- 9580464
TI  - [Emphysematous prostatitis, apropos of a case].
AB  - OBJECTIVE: To describe a case of emphysematous prostatitis in a 70-year-old male
      patient. The rarity of this condition is underscored, the diagnostic and
      therapeutic aspects are discussed and the literature briefly reviewed.
      METHODS/RESULTS: The diagnosis of emphysematous prostatitis was based on the
      findings of a plain x-ray of the pelvis, which demonstrated gas in the prostatic
      region in the AP and oblique views. The diagnosis was confirmed by transrectal
      US, which also permitted percutaneous drainage. CONCLUSIONS: A plain x-ray of the
      pelvis is simple and low-cost, and can be useful in orienting the diagnosis in
      patients with features of prostatic abscess. However, transrectal US is the
      diagnostic method of choice, which also permits treatment by percutaneous
      drainage with antibiotic protection.

PMID- 9580467
TI  - [Preconceptional control in diabetic women].
AB  - The experience of the Preconceptional Clinic developed in our hospital from 1992
      to 1996 is here reported. Twenty-eight insulin-dependent diabetic patients
      underwent a preconceptional control (PCC). Pregnancy was obtained in 19 patients
      (2 miscarriages, 12 full pregnancies, and 5 pregnancies in course). A comparative
      case-control study was performed between the 12 patients undergoing PCC, who have
      completed their pregnancy, and other 12 prepregnant diabetic patients, controlled
      from the 7-12 weeks of pregnancy. HbA1c levels in the PCC group were lower, and
      no differences regarding fetal morbidity were observed. The presence of a severe
      congenital malformation in the PCC group, with normal periconceptional HbA1c
      levels, denotes the teratogenic influence of factors yet to be elucidated.

PMID- 9580466
TI  - [Chordoma of the ethmoidal sinus. A case report].
AB  - Chordomas are dysembryogenic tumors originating from the notochordal process. The
      case of a 9-month-old male infant with involvement of the ethmoidal sinus and
      anterior fossa is reported. These tumors are rare in ENT practice and in children
      arise in the clivus. The diagnosis was made by biopsy, CT and MRI. Surgery is the
      only effective treatment, with chemotherapy and radiotherapy having little value.
      The complication and relapse rates are high.

PMID- 9580468
TI  - [Distal ischemia in the upper limbs in a patient with renal failure].

PMID- 9580469
TI  - [Luetic neuro-retinitis: therapy failure with penicillin benzathine].

PMID- 9580470
TI  - Characterization of rat exploratory behavior using the exploration box test.
AB  - A method to measure various aspects of exploratory behavior was further
      characterized using standard pharmacological treatments known to induce anxiety,
      or anxiolysis, or locomotor activation. FG 7142, an anxiogenic beta-carboline,
      induced a dose-dependent reduction in the rat exploratory behavior. A single FG
      7142 (20 mg/kg) treatment before behavioral testing had a carry-over effect on
      rats' behavioral performance on the two subsequent days. When FG 7142 (20 mg/kg)
      was administered during five consecutive days before behavioral testing, its
      anxiogenic-like effect first deepened, but waned off by the fifth session.
      Diazepam at the dose of 0.5 mg/kg had no effect of its own, but blocked the
      anxiogenic-like effect of FG 7142 (10 mg/kg) treatment. At a higher dose (1
      mg/kg), diazepam treatment reduced exploratory behavior, but this effect was not
      carried over to the drug-free sessions on the subsequent day. Buspirone and
      gepirone (both 1 mg/kg), the 5-HT1A receptor agonists, had no effect. D
      Amphetamine, a locomotion-enhancing drug which has anxiogenic-like properties in
      several tests of exploratory behavior, increased the activity of rats at the dose
      of 0.5 mg/kg, but at the dose of 1 mg/kg the only effect was a reduction in the
      number of rearings: this effect was not carried over to the subsequent retest. On
      the basis of the results described in this article and elsewhere, we suggest that
      this technique can be useful for separating a true anxiogenic drug from other
      compounds which influence exploratory activity.

PMID- 9580471
TI  - Asymmetrical oxygen availability from serosal and luminal sides of rat distal
      colon epithelium.
AB  - Short-circuit current (Isc) and transepithelial potential difference (PD) of the
      rat distal colon mucosa are sensitive to acute hypoxia in vitro. The relative
      contribution of luminal and serosal oxygenation in sustaining Isc and PD was
      assessed. Rat distal colon Isc and PD responses to hypoxia and reoxygenation of
      preparations of mucosa-submucosa, and of isolated mucosa (with and without the
      mucus gel layer), mounted in an Ussing chamber, and of sacs of everted and non
      everted isolated mucosa, were measured. In Ussing chambers, a 5-min total
      (bilateral) hypoxia reduces Isc and PD by 50 to 70%, while an overshoot was
      observed on reoxygenation. Serosal hypoxia caused about the same effect as total
      hypoxia, with complete recovery on reoxygenation. Luminal hypoxia had no effect
      in either Isc or PD. After total hypoxia, selective serosal reoxygenation allowed
      complete recovery of Isc and PD; addition of luminal reoxygenation did not
      further increase Isc and PD. Luminal reoxygenation after total hypoxia did not
      modify the decrease in Isc and PD, but addition of serosal reoxygenation led to
      complete recovery. A similar behaviour was seen in isolated mucosa preparations
      without the mucus gel layer. Baseline Isc and PD of everted sacs were about 45%
      of those of non-everted sacs, but their response to a hypoxic challenge was
      slightly attenuated. On reoxygenation, both everted and non-everted sacs showed
      complete recovery. Summing up: serosal oxygenation is both necessary and
      sufficient to sustain rat distal colon Isc and PD, while luminal oxygenation is
      not; there seems to exist a barrier, different from the mucus gel layer, for
      oxygen access from the luminal side of the epithelium; and distal colon isolated
      mucosa everted sac preparations are suboptimally oxygenated.

PMID- 9580472
TI  - Effect of dithiothreitol on mucus gel layer and electrophysiological properties
      in rat colon.

PMID- 9580473
TI  - Liver transplantation in cirrhotic patients over 60 years of age.
AB  - Although life expectancy in Spain is above seventy years, age over sixty is
      considered a relative contraindication for liver transplantation (LT) in most
      centers. The aim of this study was to assess the outcome of LT in patients over
      sixty years of age comparing them to patients under that age. From January 1992
      to August 1995, 61 cirrhotic patients underwent LT at our institution; of them,
      43 (group I) were younger than 60 years (mean +/- SEM: 51.9 +/- 0.9 years, range:
      37-59) and 18 patients (group II) were 60 years or older (64.1 +/- 0.7, range: 60
      71). Main pre-transplant variables (sex, etiology of liver disease, presence of
      hepatocarcinoma, Child-Pugh's score and renal function) were similar in both
      groups. The follow-up (median and range) for group I was 28 and 3-47 months, and
      for group II 16.5 and 3-48 months. Actuarial survival rates at one and four years
      post-LT were respectively 88.3% and 85.6% for group I, and 87.8% and 87.8% for
      the group II (p = n.s.). There were no differences between both groups regarding
      the incidence of rejection, major infections, neurologic complications, renal
      failure, pathological bone fractures, diabetes mellitus or hypertension.
      Nevertheless, cardiovascular complications were significantly more frequent in
      group II (p = 0.002) although they were not the cause of death. In conclusion,
      our results show that the outcome of LT in patients over sixty years old is
      comparable to that observed in patients under that age. LT should not be
      contraindicated on the only basis of an age greater than 60 years.

PMID- 9580475
TI  - [Leiomyoma of the greater omentum].

PMID- 9580474
TI  - [Screening for colorectal cancer predisposition].
AB  - In the last years the advantages in molecular biology have developed a variety of
      useful tests in order to detect genetic mutations. These mutations are associated
      to a susceptibility of suffering a colo-rectal cancer. The genetic tests are
      designed to screen the disease although many problems can emerge when they are
      offered to the population. In this article, we will try to analyze the
      advantages, disadvantages and the present indications for genetic testing in colo
      rectal cancer, particularity in cases of familial adenomatous polyposis and
      nonpolyposis inherited colon cancer.

PMID- 9580476
TI  - [Nodular subcutaneous fat necrosis: a rare complication of acute pancreatitis].

PMID- 9580477
TI  - Low levels of high density lipoprotein cholesterol in patients with active
      sarcoidosis.
AB  - OBJECTIVE: To determine lipoprotein abnormalities in patients diagnosed with
      sarcoidosis and their relation to disease activity. METHODS: We studied 90
      patients with biopsy-proven sarcoidosis who had not been treated with
      corticosteroids (44 with active disease and 46 with inactive disease) and 147
      control subjects. Sarcoidosis activity was evaluated by means of clinical, chest
      X-ray, gallium-67 scan, serum angiotensin converting enzyme (peptidyl-dipeptidase
      A) values, and pulmonary function tests. Analysis of lipoprotein metabolism
      included: serum cholesterol, low density lipoprotein (LDL)-cholesterol, high
      density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, HDL3-cholesterol,
      apolipoprotein A-I, apolipoprotein B, and triglyceride concentrations. RESULTS:
      Patients with active sarcoidosis had significantly low HDL-cholesterol
      concentrations (1.15 +/- 0.27 mmol/l) as compared with inactive sarcoid patients
      (1.40 +/- 0.34 mmol/l) and with the healthy control subjects (1.49 +/- 0.34
      mmol/l) (p = 0.00001). The decrease in the HDL-cholesterol concentrations seen in
      patients with active disease was due mainly to the cholesterol bound to HDL2
      subfraction. Apolipoprotein A-I concentrations were significantly reduced in the
      patients with active disease (1.18 +/- 0.32 g/l) compared to the healthy controls
      (1.38 +/- 0.27 g/l) (p = 0.003). There were no significant differences in
      cholesterol, triglyceride, LDL-cholesterol or apolipoprotein B values among the
      three groups. Multivariate logistic regression analysis showed that HDL
      cholesterol was the only variable independently associated with disease activity
      (Regression Coefficient b = -0.03; S.E. = 0.008; p = 0.0005). CONCLUSION: The
      decrease in HDL-cholesterol that is observed in patients with sarcoidosis is
      limited to those with active disease.

PMID- 9580478
TI  - Recognition of B-CLL cells experimentally infected with EBV by autologous T
      lymphocytes.
AB  - We compared 5-day-old cultures of two B-CLL clones experimentally infected with
      EBV for their interaction with autologous T lymphocytes. The clone which was
      strongly activated by the virus stimulated autologous T cells. It was also
      damaged by the cytotoxic T cells which were generated in mixed cultures with
      autologous lymphoblastoid cell lines (LCL). Cultured, non-infected CLL cells were
      not lysed by these effectors. The other B-CLL clone, which was activated to
      considerably lesser extent by the virus, did not stimulate the autologous T
      lymphocytes. While, also in this case cytotoxic function was generated in the
      mixed T cell-LCL culture, the effectors did not damage the EBV-infected CLL
      cells. The results with B-CLL cells can be regarded as a model for the EBV genome
      carrier normal B lymphocytes. They substantiate the current concept that such
      cells persist in seropositive healthy individuals undisturbed by the specific
      immune response as long as they maintain the phenotype of resting cells. However,
      after activation they can be recognized and eliminated by T cells.

PMID- 9580479
TI  - Collagen-related markers of bone turnover reflect the severity of liver fibrosis
      in patients with primary biliary cirrhosis.
AB  - The influence of a nonskeletal disease with increased connective tissue synthesis
      or degradation in the collagen-related markers of bone turnover has been
      evaluated in 34 women with primary biliary cirrhosis (PBC; age range 41-81
      years), a disease with increased hepatic fibrosis, often associated with
      osteoporosis. Serum osteocalcin (BGP), and carboxy-terminal (PICP) and amino
      terminal (PINP) propeptides of type I collagen were assessed as indexes of bone
      formation, whereas serum tartrate-resistant acid phosphatase (TRAP), and cross
      linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary
      hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), and type I
      collagen cross-linked N- (NTX) and C-telopeptide (CTX) were measured as markers
      of bone resorption. The histologic stage of the disease and serum amino-terminal
      propeptide of type III collagen (PIIINP) as an index of liver fibrogenesis were
      also evaluated. BGP levels were significantly lower, whereas PICP and PINP levels
      were higher in patients than in controls. Among the bone resorption markers,
      serum ICTP and urinary PYR, DPYR, HYP, NTX, and CTX levels were significantly
      higher in patients than in controls. Serum PIIINP levels were also increased in
      PBC patients. BGP did not correlate with PICP and PINP, but these markers of bone
      formation as well as ICTP, PYR, DPYR, and NTX correlated with serum PIIINP
      levels. Serum TRAP did not correlate with collagen-related markers of bone
      resorption. Moreover, patients with PIIINP and bilirubin above normal levels had
      higher PICP, PINP, ICTP PYR, DPYR, CTX, and NTX. These markers correlated with
      the histologic stage of the disease, but not with osteopenia measured by
      densitometric procedures in 22 patients. In conclusion, collagen-related markers
      of bone turnover do not reflect bone remodeling in PBC. The close association of
      these markers with PIIINP and the clinical and histologic stage of the liver
      disease suggests that they are influenced by liver collagen metabolism.

PMID- 9580480
TI  - Tissue specific interactions of exercise, dietary fatty acids, and vitamin E in
      lipid peroxidation.
AB  - Both physical exercise and ingestion of polyunsaturated fatty acids that play an
      essential role in free radical-mediated damages cause lipid peroxidation. The
      intake of specific fatty acids can modulate the membrane susceptibility to lipid
      peroxidation. Data confirmed that liver, skeletal muscle, and heart have
      different capabilities to adapt their membrane composition to dietary fatty
      acids, the heart being the most resistant to changes. Such specificity affects
      membrane hydroperoxide levels that depend on the type of dietary fats and the
      rate of fatty acid incorporation into the membrane. Sedentary rats fed a
      monounsaturated fatty acid-rich diet (virgin olive oil) showed a higher
      protection of their mitochondrial membranes against peroxidation than sedentary
      rats fed a polyunsaturated fatty acid-rich diet (sunflower oil). Rats subjected
      to training showed higher hydroperoxide contents than sedentary animals, and
      exhaustive effort enhanced the aforementioned results as well as in vitro
      peroxidation with a free radical inducer. This study suggests that peroxide
      levels first depend on tissue, then on diet and lastly on exercise, both in liver
      and muscle but not in heart. Finally, it appears that alpha-tocopherol is a less
      relevant protective agent against lipid peroxidation than monounsaturated fatty
      acids.

PMID- 9580481
TI  - Influence of the human immunodeficiency virus in the incidence of tuberculosis in
      a cohort of intravenous drug users: effectiveness of anti-tuberculosis
      chemoprophylaxis.
AB  - SETTING: A residential program in Barcelona for drug addicts (therapeutic
      community) admitted between November 1988 and March 1992, and followed until
      September 1994. OBJECTIVE: To study the incidence of tuberculosis as related to
      the presence of tuberculosis infection and/or human immunodeficiency virus (HIV)
      infection, and to evaluate the protective effect of chemoprophylaxis with
      isoniazid. DESIGN: Prospective cohort study. Incidence rates were compared using
      the Chi-square test for cohort studies. The effectiveness of chemoprophylaxis was
      evaluated by the Kaplan-Meier method at the univariate level, and by logistic
      regression models and proportional risks analysis at the multivariate level.
      RESULTS: During the study of 361 individuals without previous known tuberculosis
      or history of anti-tuberculosis chemoprophylaxis, 25 developed tuberculosis, an
      overall incidence rate of 1.79/100 person-years. For HIV-positive persons, the
      incidence rate was 3.25/100 person-years, compared with 0.30/100 in those who
      were HIV-negative (P < 0.05). The highest incidence rates occurred among HIV
      positive persons who did not receive chemoprophylaxis and who were either anergic
      (HIV-positive, purified protein derivative [PPD]-negative, Multitest-negative) or
      who were infected with Mycobacterium tuberculosis (PPD+), 10.0/100 person-years
      and 4.64/100 person-years, respectively. Of the 53 persons who received
      chemoprophylaxis, three developed tuberculosis, an incidence rate of 1.4/100
      person-years. In comparison, in the group of 51 patients who were designated to
      receive chemoprophylaxis but where none was actually taken, 17 developed
      tuberculosis, an incidence rate of 5.7/100 person-years (P = 0.03). CONCLUSION:
      HIV-infected intravenous drug users, particularly those who are anergic or who
      are PPD positive, are at increased risk of developing tuberculosis. Anti
      tuberculosis chemoprophylaxis proved effective in this population.

PMID- 9580483
TI  - [Medical education at Universidad de los Andes, Santiago, Chile].
AB  - Universidad de los Andes School of Medicine started in 1991 with a new medical
      curriculum aimed at providing a medical education for its students, that is, it
      attempts to give, together with technical proficiency in medical matters,
      formation of character and a strong ethical attitude. The curriculum lasts for
      seven years: five of basic, pre-clinical and clinical theoretical and practical
      courses, followed by two years of internships in Internal Medicine, Surgery,
      Obstetrics and Pediatrics, plus a four month period of an elective internship.
      The courses have an integrated design, in which each matter is presented from
      multiple perspectives, e.g. in Internal Medicine together with the clinical
      aspects of disease, the pathophysiology and the pharmacology of the drugs used
      are presented. Also the Pathology of each disease is given in coordination in the
      Pathology course. General educational matters such as Anthropology, Psychology,
      Origin of Living Beings, Theology and Medical Ethics are interspersed in the
      curriculum. An important feature is the personal counselling system, in which
      each student may choose an academic counsellor and discuss with him (her) the
      subjects of his choosing. Clinical practice is given in a system that includes
      five hospitals and five private clinics that range from general medical practice
      to Psychiatry or Ophthalmology.

PMID- 9580482
TI  - [Prognostic implications of early discharge from the coronary unit in patients
      with acute myocardial infarction].
AB  - INTRODUCTION AND OBJECTIVES: The high demand for health care has obliged Coronary
      Units to hasten the discharge of patients in less serious condition and this
      might be an influence on their prognosis. Our objective have been: a) to analyse
      the characteristics and the evolution (death or readmission) during the first
      month of patients with myocardial infarction and very early discharge from the
      Coronary Unit (stay of 2 days or less), and b) to assess the profile of very low
      risk group patients for complications who could be discharged early from the
      Coronary Unit. PATIENTS AND METHODS: A study of 978 consecutive patients who had
      been admitted for acute myocardial, in faration were divided into two groups
      according to their length of stay in the Coronary Unit (A < or = 2 and B > 2
      days). Their baseline characteristics, course of stay and vital status at month,
      were compared. A subgroup of patients at low risk was studied and complications
      that might have arisen from their early discharge from the Coronary Unit were
      assessed. RESULTS: Seventy-three patients (7.5%) died within the first two days.
      Of the remaining 905, the stay was 2 days or less for 336 patients (group A); and
      longer than 2 days for 569 (group B). Group A had a higher frequency of
      dyslipemia, Killip class I on admission, uncomplicated myocardial infarction in
      the Coronary Unit and the use of beta-blockers and had less frequency of
      diabetes, Q wave myocardial infarction, anterior infarction or the use of
      fibrinolytics. In the first month after discharge from the Coronary Unit, 10
      patients from group A and 18 patients from group B died, the rate of death or
      readmission into the Coronary Unit within 30 days was similar between both groups
      (group A = 13% and group B = 13%). A multiple regression showed that Killip class
      on admission (p < 0.001) and an uncomplicated course (p < 0.001) were
      independently related with the length of stay in the coronary unit. A subset of
      378 low risk patients (Killip I on admission, uncomplicated course in the ICU and
      age < 71 years) had no mortality at 30 days and their readmission rate in the
      first month was 4%. In this subgroup, those patients whose stay was equal to or
      less than two days were more frequently readmitted in the first week. (group A =
      9/197 [5%] and group B = 1/181 ([0.5%]; p = 0.034). CONCLUSION: Selected patients
      with myocardial infarction can be discharged very early from the Coronary Unit
      with a low risk of death. A readmission rate following discharge of some 5% must
      be allowed for these patients.

PMID- 9580484
TI  - [Growth hormones and oncogenes in mammary adenocarcinomas induced by
      medroxyprogesterone acetate in BALB/c mice].
AB  - We have studied the involvement of growth factors (GF), their receptors (GF-R)
      and oncogenes in modulating tumor growth in the medroxyprogesterone acetate (MPA)
      induced mammary tumor model in BALB/c mice. We demonstrated the presence of both
      ligands of the insulin-like growth factor family (IGF-I, IGF-II) and the two
      types of receptors (IGF-RI, IGF-RII). MPA upregulated IGF-II mRNA and protein
      levels in hormone-dependent lines (MPA-D). The progression to a hormone
      independent phenotype was accompanied by a high constitutive expression of IGF-II
      and by a significant decrease in IGF-IIR number. An antisense strategy used to
      evaluate the role of IGF in the MPA-induced growth of epithelial MPA-D cells
      showed that IGF mediate progestin-induced mammary tumor growth by
      autocrine/intracrine pathways. We also studied the role of heregulins (HRG), the
      recently identified ligands for the c-erbB3 and c-erbB4 oncogenes. HRG mRNA
      expression was restricted to tumors of ductal origin. MPA induced an in vivo up
      regulation of HRG expression. Finally, we also found that MPA may be exerting its
      proliferative effect on MPA-D lines by inhibiting the expression of transforming
      growth factor beta 1, (TGF-beta 1) and the lack of expression of TGF-beta 1 in
      hormone-independent tumors may be related to the acquisition of autonomous
      growth.

PMID- 9580485
TI  - [Clinical experience with an alpha glucosidase inhibitor (acarbose) in the
      treatment of non-insulin-dependent diabetes. Multicenter study].
AB  - BACKGROUND: Acarbose, an alpha glucosidase inhibitor is a drug used in the
      treatment of non insulin dependent diabetes mellitus, that interferes with the
      intestinal absorption of monosaccharides. AIM: To study the effect of acarbose in
      non insulin dependent diabetic patients that had an inadequate metabolic control
      with diet and sulphonylureas. PATIENTS AND METHODS: Diabetic patients received
      acarbose, 150 mg/day during four weeks and this dose was increased to 300 mg/day
      during 3 months. Afterwards, patients were followed for a period of 12 weeks
      without acarbose. Fasting and post-prandial blood glucose and glycosilated
      hemoglobin were measured sequentially during the study. RESULTS: Eighty five
      patients were recruited for the study but 64 complied with the treatment
      protocol. The age of these patients was 56 +/- 8.8 years old, their diabetes
      duration was 7.8 +/- 8.8 years and their body mass index was 27.6 +/- 3.6 kg/m2.
      During acarbose treatment, glycosilated hemoglobin decreased from 8.36 +/- 1.33
      to 7.71+ 1.7% (p < 0.001), fasting blood glucose decreased from 173 +/- 48 to 159
      +/- 59 mg/dl (p < 0.03) and post-prandial blood glucose decreased from 254 +/- 80
      to 241 +/- 80 mg/dl (NS). After discontinuing acarbose glycosilated hemoglobin
      and blood glucose levels returned to basal levels. Body weight and blood pressure
      did not change during the treatment period. Fifty nine patients had
      gastrointestinal symptoms (meteorism, flatulence and abdominal distention) that
      were mild in 59% and moderate in 39%. Episodes of hypoglycemia were not observed.
      CONCLUSIONS: Acarbose, associated to sulphonylureas is an effective drug to
      reduce blood glucose and glycosilated hemoglobin levels in patients with non
      insulin dependent diabetes.

PMID- 9580486
TI  - [Occult gallbladder disease or microlithiasis in patients with acute
      pancreatitis: a frequent clinical event].
AB  - BACKGROUND: Patients with acute pancreatitis (AP) and a normal gallbladder by
      standard echographic evaluation may have "occult" gallbladder disease or
      microlithiasis with recurrent episodes of AP. AIM: To conduct a prospective
      evaluation of patients with the diagnosis of non-biliary AP in order to detect
      "occult" gallbladder disease and to compare its clinical presentation with that
      of biliary AP. PATIENTS AND METHODS: Patients admitted with the diagnosis of AP
      to a clinical hospital were included in the study. According to an abdominal
      ultrasound study, patients were classified as having or not cholelithiasis. A
      duodenal biliary drainage was performed in 15 patients with AP and without
      gallbladder stones. RESULTS: Patients without cholelithiasis had recurrent AP
      more often than patients with biliary AP (53 and 3.3% respectively). Excessive
      alcohol ingestion did not rule out the possibility of biliary etiology. In 6
      patients, the analysis of duodenal bile showed cholesterol crystals, and
      cholecystectomy confirmed the existence of gallbladder disease in 5. All of them
      remained asymptomatic during a follow-up period of four years. One patient
      refused surgery, with subsequent development of gallstones and recurrent episodes
      of AP. In other 4 patients, gallbladder disease was confirmed by percutaneous
      gallbladder puncture or during cholecystectomy. No recurrence of AP were observed
      during the follow-up CONCLUSIONS: Microlithiasis or "occult" gallbladder disease
      accounts for at least 67% of the original "non-biliary" AP. Duodenal bile
      analysis is a useful and necessary technique for the evaluation of patients with
      "non-biliary" acute pancreatitis. Careful clinical and echographic follow-up of
      this subgroup of patients with AP is mandatory.

PMID- 9580487
TI  - Biodistribution study of the anaesthetic sodium phenobarbital labelled with
      technetium-99m in Swiss mice infected with Schistosoma mansoni Sambon, 1907.
AB  - Technetium-99m (99m Tc) is a radionuclide that has negligible environmental
      impact, is easily available, inexpensive and can be used as a radioactive tracer
      in biological experiences. In order to know the mode of action of sodium
      phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to
      the liver, we labelled sodium phenobarbital (PBBT) with 99mTc and a
      biodistribution study in infected and non-infected Swiss mice was performed. The
      PBBT was incubated with stannous chloride used as reducing agent and with 99mTc,
      as sodium pertechnetate. The radioactivity labelling (%) was determined by paper
      ascending chromatography performed with acetone (solvent). The 99mTc-PBBT was
      administered by intraperitoneal route to Swiss mice infected eight weeks before.
      The animals were perfused after different periods of time (0,1,2,3,4 hr) when
      blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult
      worms were isolated. The radioactivity present in these samples was counted in a
      well counter and the percentage was determined. The radioactivity was mainly
      taken up by the blood, kidney, liver and spleen. No radioactivity was found on
      the adult worms. We concluded that the worm shift was due to an action on the
      host of the sodium phenobarbital.

PMID- 9580488
TI  - [Prevalence of Anophelines (Diptera: Culicidae) during sunset in areas of the
      Itaipu Hydroelectric plant in Guaira county, state of Parana, Brazil].
AB  - Systematic collections of anophelines were conducted from November 1994 to August
      1995 from 18:00 to 20:00 hr using Shannon traps and human-bait along the lake
      margin which forms the Itaipu Hydroelectric reservoir, State of Parana, Brazil.
      Species prevalence was studied at 15 min intervals. Anopheles albitarsis sensu
      latu and An. galvaoi, were the most frequently collected mosquitoes. All
      Anopheles species populations peaked between 18:45 and 19:30 hr. The observations
      illustrate the existence of a haematophagic activity cycle during the early
      evening hours: exogenous stimulus (the beginning of sunset)-->Shannon trap (light
      attraction)-->human bait (haematophagy)-->rest and digestion-->exogenous stimulus
      ->Shannon trap or surrounding vegetation. The greater abundance of An. albitarsis
      collected in human-bait and Shannon trap suggests it may be a potential malaria
      vector in the region.

PMID- 9580489
TI  - Characterization of rotavirus strains with unusual electrophoretic profiles.

PMID- 9580490
TI  - TcruziDB, an integrated database, and the WWW information server for the
      Trypanosoma cruzi genome project.
AB  - Data analysis, presentation and distribution is of utmost importance to a genome
      project. A public domain software, ACeDB, has been chosen as the common basis for
      parasite genome databases, and a first release of TcruziDB, the Trypanosoma cruzi
      genome database, is available by ftp from
      ftp://iris.dbbm.fiocruz.br/pub/genomedb/Tcr uziDB as well as versions of the
      software for different operating systems
      (ftp://iris.dbbm.fiocruz.br/pub/unixsoft/). Moreover, data originated from the
      project are available from the WWW server at http://www.dbbm.fiocruz.br. It
      contains biological and parasitological data on CL Brener, its karyotype, all
      available T. cruzi sequences from Genbank, data on the EST-sequencing project and
      on available libraries, a T. cruzi codon table and a listing of activities and
      participating groups in the genome project, as well as meeting reports. T. cruzi
      discussion lists (tcruzil@iris.dbbm.fiocruz.br and tcgenics@iris.dbbm.fiocruz.br)
      are being maintained for communication and to promote collaboration in the genome
      project.

PMID- 9580491
TI  - The Trypanosoma cruzi genome project: nuclear karyotype and gene mapping of clone
      CL Brener.
AB  - By using improved pulsed field gel electrophoresis conditions, the molecular
      karyotype of the reference clone CL Brener selected for Trypanosoma cruzi genome
      project was established. A total of 20 uniform chromosomal bands ranging in size
      from 0.45 to 3.5 Megabase pairs (Mbp) were resolved in a single run. The weighted
      sum of the chromosomal bands was approximately 87 Mbp. Chromoblots were
      hybridized with 39 different homologous probes, 13 of which identified single
      chromosomes. Several markers showed linkage and four different linkage groups
      were identified, each comprising two markers. Densitometric analysis suggests
      that most of the chromosomal bands contain two or more chromosomes representing
      either homologous chromosomes and/or heterologous chromosomes with similar sizes.

PMID- 9580492
TI  - Identification of transcribed sequences (ESTs) in the Trypanosoma cruzi genome
      project.
AB  - Random single pass sequencing of cDNA fragments, also known as generation of
      Expressed Sequence Tags (ESTs), has been highly successful in the study of the
      gene content of higher organisms, and forms an integral part of most genome
      projects, with the objective to identify new genes and targets for disease
      control and prevention and to generate mapping probes. In the Trypanosoma cruzi
      genome project, EST sequencing has also been a starting point, and here we report
      data on the first 797 sequences obtained, partly from a CL Brener epimastigote
      non-normalized library, partly on a normalized library. Only around 30% of the
      sequences obtained showed similarity with Genbank and dbEST databases, half of
      which with sequences already reported for T. cruzi.

PMID- 9580493
TI  - Upper extremity skeletal muscle mass: potential of measurement with single
      frequency bioimpedance analysis.
AB  - This study examined the potential of single frequency (50 kHz) BIA for estimation
      of upper extremity skeletal muscle (SM) mass. Subjects (n = 50) were weight
      stable adults varying in age (X +/- SD, 51.6 +/- 17 yr) and body mass index (27.2
      +/- 5.9 kg/m2). Determinants of arm to arm impedance index (length L; L2/Z) were
      examined using multiple regression analysis. A good correlation was observed
      between L2/Z and arm SM estimated by dual-energy X-ray absorptiometry (r = 0.88,
      p < 0.001). Additional significant model covariates were arm fat mass (p < 0.05),
      bone mass (p < 0.01), and age (p < 0.001). These findings suggest that upper
      extremity SM may be rapidly and easily quantified using a simple and inexpensive
      BIA system combined with appropriate age-adjusted impedance prediction equations.

PMID- 9580494
TI  - Postnatal development of interlaminar astroglial processes in the cerebral cortex
      of primates.
AB  - Long astroglial processes traversing several cortical laminae appear to be
      characteristic of primate brains. Whether interlaminar processes develop as a
      modification of radial glia or are truly postnatal elements stemming from
      stellate astroglia, could be assessed by analyzing their early developmental
      stages. A survey of glial fibrillar acidic protein immunoreactive (GFAP-IR)
      astroglial interlaminar processes in the cerebral cortex of Ceboidea monkeys at
      various postnatal developmental ages, and in human cortical samples of a ten day
      and a seven year old child disclosed that such processes develop postnatally. At
      one month of age GFAP-IR interlaminar processes in monkeys were scarce and short
      in most frontal, parietal or occipital (striate) cortical areas, except for
      sulcal (principal and orbital sulci) and temporal cortical areas. Some processes
      were weakly positive for vimentin, and these were most abundant in ventral
      temporal cortical areas. At two months of age processes were present in all these
      areas, albeit in restricted patches and significantly shorter than in adults. The
      expression of this pattern was increased at seven months of age. At three years
      of age almost every area showed abundant processes and with lengths comparable to
      the adult Ceboidea individuals. In humans, at 10 days of age long interlaminar
      processes were readily apparent in a frontal cortex sample, becoming most
      apparent at the age of seven years although not reaching yet the adult
      characteristics as described previously. CONCLUSIONS: (1) GFAP-IR interlaminar
      processes develop postnatally, thus typifying a subtype of the classical stellate
      forms; (2) they bear no obvious direct relationship with radial glia; (3) their
      development is not contemporary among the various cortical regions. These long
      cellular processes represent an addition to those already described for other
      astroglial cell types in the adult mammalian brain (Golgi-Bergmann glia,
      tanicytes, Muller cells).

PMID- 9580495
TI  - Bothrops sp. snake venoms: comparison of some biochemical and physicochemical
      properties and interference in platelet functions.
AB  - Procoagulant, proteolytic, phospholipase and platelet pro-aggregating and
      inhibiting activities were screened for pooled venoms of seven Bothrops species
      as well as Crotalus durissus terrificus and Lachesis muta snakes typical of the
      Brazilian territory. As reported by other authors, we also found that examination
      of the electrophoretic and gel filtration patterns of Bothrops snakes venoms
      could not be used for identification of the species of a given venom because of
      the lack of marked interspecific differences within the same genus. Our data
      indicated that B. cotiara, B. alternatus and B. atrox possess no platelet pro
      aggregating activity, low inhibitory effect on platelet aggregation and very low
      or intermediate levels for the other activities. B. moojeni, B. neuwiedi and B.
      jararacussu whose venoms possess high procoagulant, platelet pro-aggregating and
      phospholipase activities are low in both proteolytic and platelet inhibitory
      activities. B. jararaca venom showed the highest inhibitory effect on platelet
      aggregation and very low platelet pro-aggregating activity. Compared with the
      Bothrops venoms studied, L. muta venom showed that highest proteolytic activity
      while C. d. terrificus venom presented remarkable high platelet pro-aggregating
      and phospholipase activities. In all venoms, proteolytic activity could be
      completely inhibited by EDTA (2 mM) alone. In contrast, the presence of
      phenylmethylsulfonyl fluoride (5 mM) inhibited partially the caseinolytic
      activity of all venoms, except that L. muta venom, which was almost completely
      blocked by this reagent. Altogether, these data confirm the presence of high
      levels of metalloproteinases in the venoms of Crotalinae snakes. Most of these
      enzymes are dependent of the availability of Ca2+, being much less the same
      concerning the presence of serine residues in their active sites. The data
      indicated that the presence and levels of procoagulant, azocaseinolytic and
      phospholipase A2 activities alone could not differentiated the species of the
      Bothrops venoms studied, particularly in the cases of B. jararaca, B. moojeni and
      B. atrox. However, the platelet inhibiting property of low doses of B. jararaca
      venom can be useful to differentiate it from B. moojeni venom. In the same way,
      the platelet pro-aggregating activity of high doses of B. jararaca venom may be
      used to distinguish it from B. atrox crude venom, otherwise very similar but
      incapable to activate platelets. In conclusion, our comparative screening of
      biological properties has indicated that platelet studies may serve as a tool to
      distinguish among venoms that otherwise behave biochemically in a very similar
      way. Although promising, the general applicability of platelet activation studies
      by snake venoms for classification or taxanomical purposes has yet to be extended
      to other family of snakes to be proven useful.

PMID- 9580496
TI  - Nasal myiasis due to Oestrus ovis infestation in a dog.

PMID- 9580498
TI  - XX/XY chromosome chimaerism in an intersex dog.

PMID- 9580499
TI  - Genome diversity in temperate bacteriophages of Oenococcus oeni.
AB  - The genome structure of six bacteriophages of Oenococcus oeni was compared. Two
      distinct groups with no apparent restriction site conservation were defined. In
      members of the alpha group (fOgML34, fOg4029, fOg30 and fOg218) a 7.5 kb region
      containing the origin of DNA packaging (cos) was highly conserved. Stretches of
      DNA heterogeneity could also be assigned to particular regions and were mostly
      evident in the right area of the genomes. fOg44 and fOgPSU1 (beta group) were
      indistinguishable in the left half of their genomes, including cos, but were
      markedly dissimilar in other regions. Strong labelling signals detected in cross
      hybridizations involving members of different groups were confined to fragments
      centrally located in their physical maps. The attachment site (attP) of fOg44 was
      assigned to this conserved region. It is suggested that recombination events at
      this location may have been important in generating the observed diversity of
      oenophage genomes.

PMID- 9580500
TI  - Congenital adrenal hyperplasia and early newborn screening: 17 alpha
      hydroxyprogesterone (17 alpha-OHP) during the first days of life.
AB  - OBJECTIVE: Definition of upper limits for 17 alpha-hydroxyprogesterone (17 alpha
      OHP) is important as its measurement is used in screening for congenital adrenal
      hyperplasia. This study aimed at investigating the cut off concentrations in
      relation to the day of sample collection. METHODS: 17 alpha-OHP concentration was
      determined in dried filter paper blood spots taken from cord blood and by heel
      pricking up to the sixth day of life. A sensitive fluoroimmunoassay (DELFIA)
      method was used. Samples from 1091 apparently health full term neonates were
      tested. Samples were separated according to the age of sampling. RESULTS: The 17
      alpha-OHP (nmol/l blood) (median and 97.5th centile) concentrations according to
      the age of sampling were: cord blood (n = 126) 123.7, 265.6; first day 0-6 hours
      (n = 30) 49.4, 80.3; 6-12 hours (n = 57) 42.7, 79.8; 12-18 hours (n = 58) 38.1,
      62.7; 18-24 hours (n = 67) 28.8, 49.7; second day 24-36 hours (n = 51) 23.6,
      43.3; 36-48 hours (n = 63) 19.9, 35.4; third day (n = 200) 10.6, 23.5; fourth day
      (n = 197) 8.8, 20.8; fifth day (n = 76) 6.4, 18.3; sixth day (n = 166) 6.6, 19.4.
      CONCLUSION: Cord 17 alpha-OHP concentrations were very high as previously
      described, probably owing to steroid production by fetal adrenal glands.
      Therefore, cord blood is not useful for screening purposes. Thereafter there is a
      gradual decline in 17 alpha-OHP median concentrations. A cut off value of 30
      nmol/l blood was useful in samples obtained after 48 hours of life. However, cut
      off values before 48 hours should be adjusted according to the sampling time.

PMID- 9580501
TI  - [Use of health services by a population of 60-year olds and older in Mexico].
AB  - OBJECTIVE: To describe the sociodemographic characteristics and determinants of
      health services utilization by the Mexican population of 60 years of age or more.
      MATERIAL AND METHODS: Information obtained from the National Health Survey II
      (ENSA-II) allowed analysis of 4,628 elderly people. Prevalence of chronic
      diseases was analyzed and the determinants of individuals who had used the health
      services in the two weeks prior to the interview. RESULTS: The chronic diseases
      most frequently reported were: hypertension, diabetes and heart disease. The
      utilization and hospitalization rates of that age group were 11.4 and 5.5%,
      respectively. The services most frequently used were: the private physician,
      social security (IMSS, ISSSTE) welfare services (Ministry of Health--SSA- and
      IMSS-Solidaridad). Interestingly, 25 to 45% of social security insurance holders
      did not use the services, instead they consulted a private physician. The most
      important explanatory variables for health services utilization were: the
      perceived illness, not having worked for the previous week and being a social
      security insurance holder. Gender, area of residence and level of education were
      not significant in the explanation of health services utilization. CONCLUSIONS:
      This study demonstrates the need to strengthen preventive and support programs
      for the elderly population, since they only demand health services when they feel
      sick.

PMID- 9580503
TI  - [Diagnosis and treatment of leprosy].

PMID- 9580502
TI  - [Prevalence of tuberculosis infection in students in the city of Tijuana,
      Mexico].
AB  - OBJECTIVE: To determine the prevalence of tuberculosis infection in school
      children from Tijuana, Mexico. MATERIAL AND METHODS: A study sample was randomly
      chosen from the municipal school registry and 1,131 elementary and high school
      children were included. All received one doses of PPD 5TU (Mantoux). Subjects
      with induration > or = 10 mm were considered positive reactors. RESULTS: The
      overall prevalence of positive reactors was 57%. The proportion of positive
      reactors was significantly higher among BCG-immunized subjects than in non
      immunized individuals (59.7 vs 45.6%; p < 0.001). Correlation was not significant
      between age of immunization with BCG and diameter of induration. CONCLUSIONS: The
      prevalence of tuberculosis infection in Tijuana is extremely high; this fact has
      important implications in the control of tuberculosis in this region.

PMID- 9580504
TI  - [Dilatation of the abdominal aorta in patients with ischemic cerebrovascular
      disease].

PMID- 9580505
TI  - [Prevalence and control of arterial hypertension in the adult population of the
      Valencian community, 1994].
AB  - BACKGROUND: High blood pressure (HBP) is probably one of the main targets for
      prevention in primary health care. Knowledge of the magnitude and control is
      needed for monitoring this health problem at the population level. The aim of
      this study was to estimate the prevalence of hypertension in the adult population
      of Valencian Region (VR) (Spain), and to evaluate the degree of treatment and
      control. SUBJECTS AND METHODS: Two measurements of blood pressure (BP) were
      obtained for a representative sample of 1,674 participants (14 years and older)
      in the nutrition and health survey of the VR in 1994. A semi-automatic digital
      esfingmomanometer was used. HBP definition was based on the criteria of the WHO
      and the Fifth Joint National Committee on Detection Evaluation and Treatment on
      HBP. Criteria of the MONICA project were used to determine the level of treatment
      and control of hypertension. Prevalence of HBP was estimated for sex and age
      groups accounting for the study design. RESULTS: HBP prevalence was 31.7% (14.1%
      borderline HBP plus 17.6% defined HBP). Hypertension increased with age from a
      prevalence of 9.3% in the group 15-24 years of age, to 68.8% in the group > or =
      65 years old. A 57% of hypertensive persons were not under treatment, a 16.6%
      were treated but their BP was not controlled, and a 26.4% were under treatment
      and presents controlled BP. The uncontrolled BP was more evident at younger ages.
      CONCLUSIONS: This study has shown that one third of the adult population from VR
      had HBP, and over the half of them are not treated. Furthermore, over one third
      of hypertensives under pharmacological treatment presented uncontrolled BP. These
      results should be taken into account if preventive actions are to be implemented
      at the individual and population level.

PMID- 9580506
TI  - [Diarrhea associated with Clostridium difficile].

PMID- 9580507
TI  - [Influence of levels of vitamin B2, B12, and folic acid on the values of basal
      homocysteinemia and after methionine overload].

PMID- 9580508
TI  - [Homocysteinemia as a risk factor for vascular disease-which patients should be
      treated?].

PMID- 9580509
TI  - [Transient hypertrophic neonatal myocardiopathy after acute fetal distress].
AB  - Hypertrophic cardiomyopathy is rare in neonates. The causes include metabolic
      disease, maternal diabetes, dexamethasone therapy in premature newborns for
      bronchopulmonary dysplasia and idiopathic hypertrophic cardiomyopathy. The
      authors present a case report regarding a neonate with transient hypertrophic
      cardiomyopathy, after acute fetal distress. Signs of congestive cardiac failure
      appeared at day 1. Echocardiography showed signs of mild pulmonary hypertension
      and normal ventricular wall thickness. Echocardiography on day 2 showed
      hypertrophy of myocardial walls affecting first the right ventricular anterior
      wall and the interventricular septum, followed by the left ventricular posterior
      wall. With therapy, clinical improvement was noted on day 4. The ventricular wall
      thickness was almost normal at three weeks. The authors alert physicians to the
      importance of echocardiographic examination of these neonates.

PMID- 9580510
TI  - Study on the possible involvement of protein kinases in the modulation of brain
      presynaptic sodium channels; comparison with calcium channels.
AB  - A possible modulatory role of kinases on voltage sensitive Na+ channels of
      presynaptic brain nerve endings was investigated by testing the effect of several
      kinase activators and inhibitors on the elevation of [Nai] induced by veratridine
      in mouse brain synaptosomes loaded with a selective Na+ indicator dye.
      Veratridine (20 microM) increases the basal [Nai] level (20 mM) more than
      twofold. This increase is independent of external Ca2+, but abolished by
      tetrodotoxin (1 microM). Activation of cAMP dependent protein kinase with
      forskolin or cAMP analogs, or of protein kinase C with diacylglycerol did not
      affect the veratridine-induced elevation in [Nai]. Drugs reported to inhibit
      calmodulin-dependent events, as well as the regulatory domain of protein kinase
      C, were potent and effective inhibitors of the increase in [Nai] induced by
      veratridine, as well as other veratridine induced responses, namely elevation of
      [Cai] (monitored with the Ca2+ indicator dye fura-2) and neurotransmitter (GABA)
      release. Drugs that inhibit kinases by binding to the catalytic site were
      ineffective, however, as was the phosphatase inhibitor, okadaic acid. A selective
      inhibitor of Ca2+ and calmodulin dependent protein kinase II also did not affect
      the elevation of [Nai] induced by veratridine, but markedly diminished the
      elevation of [Cai] induced by depolarization either with veratridine or with high
      K+ (15 and 30 mM). On the basis of these results it is concluded that, the
      dramatic inhibition exerted by some of the drugs tested on the elevation of [Nai]
      induced by veratridine is not due to their effects on kinases, but to a possible
      interaction of these compounds with an intracellular site of the Na+ channel. On
      the other hand, while Ca2+ and calmodulin dependent protein kinase II is unable
      to modulate brain presynaptic voltage sensitive Na+ channels, it facilitates the
      activation of brain presynaptic voltage sensitive Ca2+ channels.

PMID- 9580511
TI  - [Clinical and epidemiological spectrum of Mycoplasma pneumoniae infections at a
      pediatric hospital].
AB  - OBJECTIVE: The objective of this study was to determine the epidemiology of
      Mycoplasma pneumoniae infections at our hospital and to evaluate the prescription
      of macrolides to empirically treat respiratory infections in children. PATIENTS
      AND METHODS: A one year prospective study was performed. To find out the
      prevalence of M. pneumoniae infections, we obtained blood samples of 519 children
      attending our hospital out-patient department to determine M. pneumoniae IgG
      levels. In order to establish the incidence, IgM antibodies against M. pneumoniae
      were measured in 255 children admitted to the hospital showing clinical pictures
      compatible with this infection. RESULTS: In the first years of life, prevalence
      of M. pneumoniae infection was low. According to our study, only 3.3% of 1 year
      old patients had M. pneumoniae antibodies. Antibody levels increased in children
      of 5 years or older. The highest rates, between 58.5% and 63.3%, were detected in
      patients between 8 and 12 years of age. The incidence rate (6.7%) was low among
      the children admitted. The most frequent clinical entity was pneumonia (82%). The
      highest rate of infection was found in children of 8 to 10 years. Symtomatology
      was mainly sub-acute. Crioagglutinins provided the most significant predictive
      value for etiological diagnosis. CONCLUSIONS: M. pneumoniae infections gain
      significance in patients over 5 years of age. In our environment, incidence of
      acute symptomatic infection is low. We consider that both age and presentation of
      acute respiratory processes should be taken into account when establishing
      empirical macrolide treatment in children.

PMID- 9580513
TI  - [Congenital short colon syndrome].

PMID- 9580512
TI  - [Acute respiratory infections in pediatric intensive care units. A multicenter
      prospective study].
AB  - OBJECTIVE: The purpose of this study was to know the etiology, clinical
      background, treatment an evolution of severe infectious diseases in children
      admitted to Pediatric Intensive Care Units (PICUs). PATIENTS AND METHODS: A
      multicenter prospective study was carried out. Children with respiratory
      infections admitted to 10 PICUs throughout Spain between May 1994 and April 1995
      were included in a long term survey. The nosocomial infections were not included.
      Student's t and Wilcoxon tests were used for quantitative variables and Chi
      square with Yates correction and Fisher's test for the qualitative variables.
      RESULTS: One hundred twenty-two patients with acute respiratory infections were
      studied. The mean value on Downes score at admittance was 5.2 +/- 2.3. Diagnosis
      were allocated as follows: 47 bronchopneumonia (38.5%), 40 bronchiolitis (33%),
      15 epiglotitis (12%), 14 laryngitis (11.5%) and "others" 6 (5%). Etiologic agents
      were identified in 69 cases (56.5%), with respiratory syncytial virus being the
      most frequently isolated agent (35 cases, 51%), followed by Hemophilus influenzae
      in 13 cases (19%). The mean PICU stay was 5.8 +/- 7.9 days (1-67 days). Of these
      cases, 112 (92%) recovered completely and 9 (7%) died (8 with bronchopneumonia
      and 1 with epiglotitis). A significant association could be seen between the
      increase in mortality and the variables Downes' score and diagnosis of
      bronchopneumonia. CONCLUSIONS: The most frequent respiratory infections in the
      PICU were pneumonia and bronchopneumonia. Viral etiology, with a frequency of
      54%, was the main cause of respiratory infection. Bacterial etiology represented
      46% of the total cases, with Hemophilus influenzae as the most frequent etiologic
      agent.

PMID- 9580514
TI  - [Growth hormone treatment of short colon syndrome].

PMID- 9580515
TI  - [Left lateral cervical tumor].

PMID- 9580516
TI  - [Prevalence of smoking among adolescent students in Navarra].
AB  - This paper reports the prevalence of smoking among adolescent students in
      Navarra, analyzing the data by sex and geographic area. A sample representative
      of Navarran adolescent school children between 12 and 18 years old was
      identified. The prevalence of smoking was measured by way of an anonymous self
      administered questionnaire filled out at school. A chi 2 test and analysis of
      variance were performed. Three hundred students (180 girls, 51.43%; 170 boys,
      48.57%) were surveyed. Mean ages were 14.35 +/- 1.82 and 14.15 +/- 1.93 years,
      respectively. Smoking prevalence was 35% among girls in the Foral Community of
      Navarra and 28.82% among the boys. The age of initiation to smoking and frequency
      of smoking are analyzed for the five geographic areas of the Navarra province.
      The prevalence of smoking is higher among girls. Children are tending to start
      smoking at earlier ages (primary school). No differences in smoking frequency
      were observed for rural and urban areas.

PMID- 9580517
TI  - [Fiber optic bronchoscopy in extraction of tracheo-bronchial foreign bodies in
      adults].
AB  - The aim of this study was to determine the clinical, radiologic and endoscopic
      characteristics of adults with tracheobronchial foreign bodies (FB), and to
      review the role of fiberoptic bronchoscopy in extracting them. We reviewed the
      case histories and bronchoscopic reports for all patients over 14 years of age
      with FB treated between 1976 and 1995. Fifty-nine FB were removed from 56
      patients; 68% were male and 48% were over 60 years of age. The most common
      clinical presentations were symptoms of respiratory infection and acute choking.
      In only in 28% could a risk factor for aspiration be identified. The X-ray was
      non specific and in 37% of cases the chest film was normal. In 66% FB aspiration
      was an unexpected endoscopic finding. The FB was removed from the right lung in
      81.3%. FB were food items in 71% of cases. Fiberoptic bronchoscopy was useful for
      removal in 95% of cases, with few and unimportant complications. Two cases were
      resolved with rigid bronchoscopy and only one patient required surgery. FB
      aspiration is common and diagnosis is difficult in the adult. Fiberoptic
      bronchoscopy resolved most aspirations in adults with no important complications.
      The rigid bronchoscope should be reserved for very specific cases.

PMID- 9580518
TI  - [Cellular homogeneity in diverse portions of the diaphragm].
AB  - The diaphragm is the main inspiratory muscle. It is composed of two parts, the
      costal and crural, with both anatomical and functional differences. The general
      morphometric characteristics of the diaphragm have been described in various
      species but homogeneity throughout the muscle has not been adequately studied.
      The aim of this study was to evaluate the fiber phenotype of various parts of the
      diaphragm. The entire diaphragm muscles of five New Zealand rabbits were removed
      and each was divided into quarters. The specimens were processed for morphometry
      (hematoxyllineosin stains, NADH-TR and ATPase at pH levels of 4.2, 4.6 and 9.4).
      For each portion we measured percent and size of fibers, expressing the latter as
      minimum diameter (Dm), measured area (Ar) and calculated area (Ac). Left and
      right diaphragm hemispheres (20 portions examined) were similar for fiber
      percentages and sizes. For left and right halves, respectively 50 +/- 2 and 51 +/
      4% of fibers were type I; type I Dm measurements were 38 +/- 5 and 41 +/- 4
      microns; type I Ar values were 1798 +/- 481 and 2030 +/- 390 micron 2; type I Ac
      values were 1181 +/- 360 and 1321 +/- 382 micron 2; type II Dm values were 46 +/-
      4 and 46 +/- 5 microns; type II Ar values were 2466 +/- 388 micron 2 and 2539 +/-
      456 micron 2; type II Ac data were 1642 +/- 255 and 1655 +/- 382 micron 2. We
      likewise found no differences between costal and crural portions of the muscle (n
      = 20). For costal and crural portions, respectively, 50 +/- 3 and 50 +/- 2% of
      fibers were type I; type I Dm sizes were 39 +/- 5 and 40 +/- 4 microns; type I Ar
      measurements were 1859 +/- 521 and 1964 +/- 365 micron 2; type I Ac figures were
      1231 +/- 317 and 1266 +/- 288 micron 2; type II Dm were 47 +/- 4 and 44 +/- 3
      microns; type II Ar were 2563 +/- 481 and 2430 +/- 331 micron 2; type II Ac were
      1729 +/- 373 and 1557 +/- 212 micron 2. Type II fibers, however, were somewhat
      larger than type I fibers in all portions (p = 0.001). New Zealand rabbit
      diaphragm muscle has similar percentages of slow and rapid contraction fibers.
      The size is not different from that observed in other species of mammals of
      similar size. Fiber type proportions are similar throughout the muscle, with more
      type II fibers present in all areas. The morphometric characters, therefore,
      suggest an homogeneous throughout the diaphragm, suggesting homogeneous response
      of the muscle to usual loads, and also suggesting the possibility of proposing
      longitudinal morphometric studies using this species as a model.

PMID- 9580519
TI  - [Multifocal inflammatory pseudotumor of the lung with good response to
      corticoids].
AB  - A 75-year-old woman was admitted to our hospital with persistent fever,
      productive cough and systemic symptoms of two months' duration. A chest film
      showed bilateral infiltration in the form of subpleural plaques with multiple
      satellite nodules in both lung fields. The biopsy specimens taken by thoracoscopy
      were compatible with inflammatory pulmonary pseudotumor. Lung resection was ruled
      out because the lesions were bilateral and corticosteroid treatment was instated.
      The clinical and radiologic response was excellent and the patient was
      asymptomatic after 30 months of low-dose corticoid therapy.

PMID- 9580520
TI  - [An epidemiologic study of pathogenic agents found in acute exacerbations of
      chronic bronchitis in northern Spain].

PMID- 9580521
TI  - GABA(B) receptor gene expression in monkey thalamus.
AB  - Expression of gamma-amino butyric acid type B (GABA[B]) receptor gene transcripts
      was examined in the macaque monkey thalamus by in situ hybridization, using
      monkey-specific cRNA probes. GABA(B) transcript expression was widespread and of
      much higher density in the dorsal thalamus than in the reticular nucleus and
      other parts of the ventral thalamus and was highest in the epithalamus. In the
      dorsal thalamus, highest mRNA levels were found in the anteroventral nucleus and
      in the parafascicular nucleus. Sensory relay nuclei showed moderate GABA(B) mRNA
      levels. Neurons of all sizes were labeled, suggesting expression in relay cells
      and interneurons, and there was no labeling of neuroglial cells. Following 10-day
      periods of monocular deprivation, levels of GABA(B) mRNA were decreased in the
      deprived magno- and parvo-cellular laminae of the dorsal lateral geniculate
      nuclei, indicating activity-dependent regulation. High levels of GABA(B)
      receptors in the dorsal thalamus are likely to reflect the high density of
      synaptic inputs from the reticular nucleus while low expression in the reticular
      nucleus implies weak, GABA(B)-mediated intrareticular inhibition.

PMID- 9580522
TI  - Bone scan in Camurati-Engelmann disease.

PMID- 9580523
TI  - Hypersensitivity pneumonitis induced by Penicillium notatum antigens in guinea
      pigs.
AB  - Data concerning the experimental induction of hypersensitivity pneumonitis in
      guinea pigs using a glycoprotein derived from Penicillium notatum are presented.
      This antigen was obtained from the mycelial and metabolic products of the
      cultures passed through a Sephadex G-50 column. It was aerosolized for inhalation
      by adult guinea pigs for 12 weeks to detect specific serum IgM, IgG and IgE
      antibodies as well as sensitized leukotriene CD4 cells. Histopathological studies
      of the lungs showed interstitial infiltrates of macrophages and leukotriene
      cells, cellular bronchiolitis and single non-necrotizing granulomas. The results
      from this animal model suggest that this hypersensitivity pneumonitis is a
      typical delayed-type reaction due to chronic contact with the heterologous
      glycoprotein of Penicillium.

PMID- 9580524
TI  - Is the histamine skin test inhibited by prednisone?
AB  - BACKGROUND: A clinical trial was carried out to determine whether therapeutic
      doses of prednisone could inhibit the response to the histamine skin test.
      METHODS: Forty-five male and female asthmatic and allergic patients participated
      in the study, their ages ranged from 6-14 years old (16 girls and 29 boys). The
      clinical trial was random, double-blind, and placebo-controlled. METHODS: Three
      treatment groups were formed and patients were assigned randomly to them. Groups
      A and B received prednisone at 0.5 and 1 mg/kg/day, respectively, whereas group C
      received a placebo (p.o.). All treatments lasted for 10 days. The histamine test
      was applied on the first, fifth and tenth days of treatment, and the size of the
      wheal and the extension of the flare were evaluated 5 min after the application
      of the test. The statistical tool used was ANOVA, since the study sought to see
      the difference among the treatment groups, after including 45 patients in three
      groups of 15 patients each. RESULTS: No significant statistical difference was
      observed among the groups using an ANOVA test. CONCLUSIONS: It was concluded that
      the response to the histamine test was not modified by a 10-day treatment with
      prednisone at doses of 0.5 mg/kg/day and 1 mg/kg/day.

PMID- 9580525
TI  - An improved histochemical technique for differentiating adrenaline- and
      noradrenaline-containing cells.
AB  - BACKGROUND: Sevki's histochemical technique allows specific staining of
      catecholamine-containing cells, yet discrimination between adrenaline-(ADR-)
      cells and noradrenaline-(NOR-) cells is unreliable, being based on hue
      differences. METHODS: In this work, histochemical differentiation of ADR- and NOR
      cells in rat adrenal medulla was carried out by introducing two modifications to
      Sevki's technique: 1) employment of aged Giemsa solution, and 2) addition of an
      alkaline differentiating step. RESULTS: With these changes, ADR-cells stained
      brown, whereas NOR-cells were deep-green, resulting in a clear-cut
      differentiation. CONCLUSIONS: The modified technique permits to differentiate ADR
      from NOR-cells in the adrenal medulla using only a bright field microscope
      without any sophisticated equipment. The present procedure is inexpensive and
      easy to carry out.

PMID- 9580526
TI  - Isolated kidney controlled perfusion with true physiological pulsatile waveform.
AB  - A computer controlled perfusion system has been developed to study the behavior
      of perfused kidneys in several conditions. The system is designed to perform
      kidney perfusions at constant pressure and low temperature (about 4 degrees C).
      We compared 2 types of perfusion pumps, a classical roller pump widely used in
      hemodialysis circuits and a vacuum powered tubular pump with active valves
      developed by our group and able to produce a flow pattern very similar to the
      pulse wave in the human circulatory system. In this preliminary study, we show
      the hydrodynamics obtained with both pumps in isolated hypothermic kidneys
      perfused with this system. The different flow patterns with both pumps seem to
      determine differences in the preservation conditions of the kidney.

PMID- 9580527
TI  - Mucinous metaplasia of apocrine duct.
AB  - Mucinous syringometaplasia is a rare condition characterized by the presence of
      mucinous cells lining eccrine ducts. Because most occurrences are on the palms
      and soles, the disorder is generally considered to be the result of chronic
      trauma or pressure. We describe an example of mucinous metaplasia involving an
      apocrine duct on the left arm of a 57-year-old woman. Histopathologic study
      demonstrated that in deeper areas of the invagination, the lining of the lumen
      consisted of columnar cells showing decapitation secretion and that the
      invagination was connected to a rudimentary hair follicle. These histopathologic
      features support the possibility that the involved duct was an apocrine one. We
      discuss the differential diagnosis with those cutaneous adnexal neoplasms in
      which the presence of mucinous cells has been described.

PMID- 9580529
TI  - [Control of hypertensive crisis with urapidil in two cases of adrenalectomy].
AB  - We review the use of urapidil to manage hypertension in two patients undergoing
      adrenalectomy for pheochromocytoma and aldosterone producing adenoma. Bolus
      administration (25 mg/i.v.) of urapidil provided good control of blood pressure
      during surgical manipulation of the tumor, although continuous perfusion of the
      drug was required by one patient before complete excision was achieved. No
      changes in heart rate or sudden decrease in blood pressure were observed. We
      believe that urapidil may be useful for treating hypertension during tumor
      adrenalectomy.

PMID- 9580528
TI  - Rupture of mitral chorda tendinea following blunt chest trauma.
AB  - Acute mitral insufficiency, originated from rupture of mitral chordae tendineae
      secondary to nonpenetrating thoracic trauma, is an unusual condition. This
      diagnosis is difficult to establish because physical examination,
      electrocardiogram, and cardiac enzymes are neither sensitive nor specific. The
      diagnosis of rupture must be quickly established because this disorder may be
      fatal. This paper reports the case of a patient with acute mitral insufficiency
      secondary to a mitral valve chord rupture a week after a nonpenetrating thoracic
      trauma.

PMID- 9580530
TI  - [Histamine liberation in the recovery unit after administration of mivacurium by
      continuous infusion].

PMID- 9580531
TI  - [Anesthesia in massive bronchial lavage].

PMID- 9580532
TI  - Cloning of a cdc2-related protein kinase from Trypanosoma cruzi that interacts
      with mammalian cyclins.
AB  - Two cdc2-related protein kinases (crk), tzcrk3 and tzcrk1, from the protozoan
      parasite Trypanosoma cruzi were cloned. tzcrk3 encodes a 35 kDa protein sharing
      51.5% amino acid identity with human cdc2 and 82% identity with Trypanosoma
      brucei CRK3. tzcrk1 encodes a 33 kDa protein sharing 52.7% identity with human
      cdc2 and a high degree of identity (> 78%) with T. brucei CRK1, Leishmania
      mexicana CRK1 and Trypanosoma congolense CRK1. A recombinant TzCRK1 protein was
      able to phosphorylate histone HI and retinoblastoma protein. Western blotting
      using a polyclonal antibody raised against the recombinant TzCRK1 protein showed
      that the kinase is present in all life cycle stages of the parasite. A PSTAIRE
      antiserum detected proteins of 32, 33 and 35 kDa, with differential expression in
      the life cycle of the parasite. Transfection of COS-7 cells with tzcrk1
      demonstrated for the first time that a CRK protein can bind mammalian cyclins;
      TzCRK1 co-immunoprecipitated with cyclins E, D3 and A suggesting a role for this
      kinase in cell cycle control. These results indicate that T. cruzi might have
      cyclin homologues that control the activity of the CRK proteins and that a
      complex mechanism would exist in order to regulate the kinases involved in the
      cell cycle and the differentiation processes of the parasite.

PMID- 9580533
TI  - Increased resistance to quinolones in Campylobacter jejuni: a genetic analysis of
      gyrA gene mutations in quinolone-resistant clinical isolates.
AB  - Campylobacter jejuni is a frequent cause of enteritis and sometimes it requires
      antimicrobial therapy. We have studied the evolution of resistance to nine
      antibiotics from 1990 to 1994 and investigated how frequently gyrA mutations are
      involved in the acquisition of quinolone resistance. The percentage of
      chloramphenicol-, clindamycin-, tetracycline- and amoxicillin plus clavulanic
      acid-resistant strains has remained practically unchanged and erythromycin and
      gentamicin resistance has decreased, whereas the percentage of ampicillin-,
      nalidixic acid- or ciprofloxacin-resistant strains has almost doubled in the
      follow-up period, from 56 to 76% for ampicillin- and from 47.5 to 88% for
      quinolone-resistant strains. This study clearly shows that a mutation in Thr-86
      to Ile or Lys is a frequent mechanism associated with the acquisition of a high
      level of resistance to quinolones in clinical isolates of C. jejuni.

PMID- 9580535
TI  - Angiotensin-converting enzyme gene polymorphism and antiproteinuric response to
      renoprotective therapy.

PMID- 9580534
TI  - Risk behaviors, HIV seropositivity, and tuberculosis infection in injecting drug
      users who operate shooting galleries in Puerto Rico.
AB  - This study was designed to assess HIV risk behaviors, HIV seroprevalence, and
      tuberculosis (TB) infection in shooting gallery managers in Puerto Rico. The
      subjects were 464 injection drug users (IDUs), of whom 12.5% reported managing
      shooting galleries. The median frequency of drug injection was higher in shooting
      gallery managers than in nonmanagers. A trend was observed for purified protein
      derivative (PPD) reactivity to increase according to the length of time spent as
      a gallery manager, but this trend was not statistically significant. However,
      anergy rates increased significantly with increase in the number of months spent
      as shooting gallery manager (p = .021). Multivariate analyses showed that IDUs
      reporting shooting gallery management experience of > or = 25 months were more
      likely to be infected with HIV. Prevention programs need to emphasize strategies
      to protect the health of shooting gallery clients and, in particular, shooting
      gallery managers. Additional studies are required to determine effective
      strategies for reducing the risk of HIV and TB infection in shooting galleries.

PMID- 9580536
TI  - Are there any differences in the parathyroid response in the different types of
      renal osteodystrophy?
AB  - With the purpose of studying the curve of parathyroid response to variations of
      serum calcium during dialysis, we studied 20 patients on haemodialysis: 10 women
      and 10 men, with different forms of bone disease diagnosed by bone biopsy
      (adynamic bone disease, mild hyperparathyroidism, severe hyperparathyroidism). In
      all patients, we performed parathyroid stimulation by 4 h dialysis with 1 mEq/l
      of Ca2+ in the dialysate, and an inhibition test in another dialysis session with
      4 mEq/l of Ca2+, with a 48 h interval. Ca2+ and intact parathyroid hormone (iPTH)
      were measured prior to dialysis and every hour subsequently, to obtain a Ca2+
      iPTH for each patient. The analysis of the curves was made using Brown's four
      parameter model. Stimulation and inhibition levels were similar in all groups,
      but basal iPTH and the response profiles obtained varied in the different
      histological groups. Basal, maximal and minimal iPTH were lower in adynamic forms
      than in the other two groups (P<0.04), and basal calcium was higher than basal
      calcium of severe hyperparathyroidism, expressing a basal inhibition status. In
      severe hyperparathyroidism, basal calcium was lower than the set-point, showing a
      permanent stimulation, and the slope was higher than in other groups, showing
      more sensitivity to serum calcium variations. The set-point of severe
      hyperparathyroidism was significantly higher than the set-point of mild and
      adynamic forms. In conclusion, the functional parathyroid study showed a
      different response in the different forms of renal osteodystrophy.

PMID- 9580537
TI  - Can we use 99mTc-MIBI in functional studies of the parathyroid gland?
AB  - The usefulness of technetium-99m-sestamibi (99mTc-MIBI) in patients with
      secondary hyperparathyroidism on haemodialysis was assessed. We studied 33
      patients with parathyroid scintigraphy with i.v. (99mTc-MIBI). Static images in a
      scintillation camera were taken at 15 and 120 min after the injection. With P x
      Ca<80, we performed an inhibition test with calcitriol i.v. 2 microg, three times
      a week, for 2 weeks. The MIBI study and assessment of intact parathyroid hormone
      (iPTH) were performed before (baseline study) and after inhibition. A 'focal
      positive study' corresponded to one or more areas of abnormal hypercaptation in
      relation to surrounding thyroid tissue seen in early images and persisting in
      later images, and a 'negative study' did not correspond to the previous image. In
      the baseline study, iPTH in the positive MIBI group was significantly greater
      than in the negative group. Eight positive MIBI patients had a bone biopsy; six
      corresponded to severe osteitis fibrosa and two to mild osteitis fibrosa. In the
      negative MIBI group, four of the six patients who had bone biopsy had mild forms
      of osteitis fibrosa (Fisher=0.03); the other two had low turnover forms. A
      positive inhibition test was defined when the basal uptake disappeared after
      calcitriol administration. In these patients, we observed a significant decrease
      of iPTH, not observed in the negative inhibition test. In 10 patients who had
      been parathyroidectomized, those with alpha positive basal MIBI result had a
      nodular parathyroid hyperplasia. We conclude that a scintigraphic parathyroid
      study with 99mTc-MIBI showed a good correlation with functional parathyroid
      status. With the same inhibition test, only some glands were inhibited,
      suggesting that this could be the expression of different vitamin D receptor
      densities in inhibited glands and/or a different kind of proliferation in those
      glands. This test would be of value in functional studies when a therapeutic
      decision must be made.

PMID- 9580538
TI  - Aluminium removal with the double chamber technique: paired filtration-dialysis
      (PFD).
AB  - Several dialysis techniques have been used to improve aluminium removal. So far
      there are no data available using paired filtration-dialysis (PFD). In this
      study, we evaluated the aluminium removed by PFD in two phases. Bovine plasma
      with known concentrations of aluminium and desferrioxamine was used in both
      experiments. In phase I, the aluminium removal was investigated using the PFD
      system (single pass) in its usual configuration, modifying the order of the
      convective and diffusive processes, dialysis with high permeability membranes and
      dialysis with low permeability membranes. During the second phase, the experiment
      lasted longer using recirculation, and the PFD was compared with conventional
      dialysis using high permeability membranes. Changes in the PFD configuration did
      not alter the aluminium removal; the efficiency of PFD for aluminium removal was
      very close to that of dialysis with high permeability membranes and much greater
      than with low permeability membranes. The aluminium is removed mainly in the
      first part of the dialysis. Aluminium mobilization using the double chamber
      technique (PFD) was efficient and might be of value for those patients with
      aluminium overload who needs high depurative techniques and are unable to
      tolerate high-flux techniques.

PMID- 9580539
TI  - Intralesional methotrexate in solitary keratoacanthoma.

PMID- 9580540
TI  - Depression of FSH and LH secretion following pulsatile GnRH administration in
      ovariectomized women.
AB  - To investigate the mechanism by which pulsatile administration of gonadotrophin
      releasing hormone (GnRH) modifies secretion of luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH), we studied three groups of five women who had
      been ovariectomized for non-malignant gynaecological conditions at least 6 months
      previously, none of whom had received substitutional hormone therapy. Before and
      after 15 day treatment with subcutaneous pulsatile GnRH (one 20 microg dose every
      90 min in group A, one 10 microg dose every 90 min in group B and one 20 microg
      dose every 120 min in group C), pulsatile secretion of LH and FSH was
      characterized by determining these hormones in 4 ml blood samples taken every 10
      min for 8 h (9.00 a.m. to 5.00 p.m.). For both LH and FSH, mean serum
      concentration and pulse amplitude were lower after GnRH treatment than before
      (and in the case of LH the decrease depended upon both the size and frequency of
      exogenous GnRH pulses) but in no group was there a significant change in LH or
      FSH pulse frequency. We conclude that exogenous pulsatile GnRH probably acts by
      partially desensitizing the pituitary rather than by depressing endogenous GnRH
      secretion. Such partial desensitization would explain reports that exogenous
      pulsatile GnRH improves ovulation by women with polycystic ovary syndrome.

PMID- 9580541
TI  - The spectrum of acute renal failure in the intensive care unit compared with that
      seen in other settings. The Madrid Acute Renal Failure Study Group.
AB  - Acute renal failure (ARF) is at a crossroads between nephrology and intensive
      care medicine. However, there seems to be wide differences between the ARF
      observed in the intensive care unit (ICU) compared to that observed in other
      areas of the hospital, particularly when examining the mortality rate. Among the
      ICU patients the 70% mortality rate is higher to the 50% found in an overall
      series of studies. Recently, Druml proposed that there is a changing trend in the
      clinical spectrum of ARF as a convincing reason to justify these differences.
      According to him, we are moving from an ARF seen as a mono-organ failure to
      another one observed in a multiorgan dysfunction syndrome (MODS) context.
      Although extremely coherent, this hypothesis has not been fully confirmed in a
      prospective study. In fact, most authors seem to look at the problem from
      opposite sides of the river, either from the critical medicine or the
      nephrological bank. To the best of our knowledge, only one retrospective study
      has dealt with this topic by comparing outcome of ARF in ICU and non-ICU
      patients. In this article we aim to overcome this problem by reviewing the data
      of the prospective epidemiological ARF study carried out in Madrid using two
      different approaches: (1) comparing the ARF cases observed in the ICU setting
      with those ARF studied outside the ICU, and (2) comparing the outcome of isolated
      ARF with the outcome of ARF as part of a MODS in patients treated in both
      settings.

PMID- 9580542
TI  - Pregnancy in women on chronic dialysis. A single-center experience with 17 cases.
AB  - Successful pregnancy outcome is an uncommon occurrence in women requiring chronic
      dialytic treatment, and the most adequate dialysis therapy in the management of
      these pregnant patients has not been established. During the period 1988-1995, we
      studied the outcome of 17 pregnancies in dialyzed females, with an average age of
      28.2 +/- 5.9 years (range: 18-38 years). Seven women had adequate urine volume
      (>800 ml/24 h). Five patients started dialysis after conception and the remaining
      12 pregnancies were diagnosed after 6-72 months on dialysis. Fourteen women were
      maintained on hemodialysis (HD) and 3 on continuous ambulatory peritoneal
      dialysis (CAPD). The HD schedule was increased to 3 h 5-6 times weekly, and CAPD
      was increased to six 2-liter exchanges/day. Mean serum urea was 78.6 +/- 27.4
      mg/dl (range 45-110); serum creatinine was 6.5 +/- 3.7 mg/dl (3.3-9.8 mg/dl); and
      hematocrit was 28.9 +/- 3.3 vol% (22-35 vol%). Anemia was partially controlled
      with rHuEpo in 8 patients. Significant problems were polyhydramnios in 7 cases (5
      HD/2 CAPD), oligohydramnios in 1 (HD), gestational diabetes in 2 (CAPD),
      premature labor with spontaneous abortion at the 19th, 22nd and 28th weeks of
      gestation (2 HD/1 CAPD), hypertension in 8 (7 HD/1 CAPD), and sterile
      eosinophilic peritonitis in 1 case (CAPD). Mean gestational age at delivery in 14
      successful pregnancies (12 HD/2 CAPD) was 32.3 +/- 2.6 weeks (27-36 weeks) and
      mean baby weight was 1,400.7 +/- 579.1 g (range 720-2,650 g). No congenital fetal
      abnormality was observed. Respiratory distress was observed in 6 infants, with 2
      deaths (1 HD/1 CAPD) in the first week after delivery. In this study, successful
      pregnancies were reported in 70.6% of dialyzed women with uremia, with
      hemodialysis having a rate of fetal survival of 78.6% and CAPD with 33.3%.

PMID- 9580543
TI  - p53 oncoprotein as a prognostic indicator in patients with breast cancer.
AB  - p53 is a tumor suppressor gene located on the human chromosome 17 that is thought
      to regulate (suppress) the proliferation of normal cells. The mutant protein
      accumulates in the nuclei of tumor cells that may then have a proliferative
      advantage over normal cells. The purpose of this study was to investigate the
      relationship between levels of mutant p53 expression and the clinical outcome of
      patients with node-positive and node-negative breast cancer. Expression of mutant
      p53 was evaluated in 655 human breast carcinomas (349 node-positive and 306 node
      negative patients) with long-term clinical follow-up by immunohistochemistry in
      sections from paraffin embedded tumors. RESULTS: Immunoreactivity was found in
      37.3% of breast tumors. There was no significant correlation between the
      expression of p53 and tumor size, nodal involvement, age or histological type.
      However, p53 overexpression was clearly related to histological grade and steroid
      receptors, with a trend to higher overexpression in ER-tumors or in those with a
      high histological grade (p < 0.01). On univariate analysis positive tumors were
      associated with reduced DFS in the total group (p < 0.001) as well as in node
      positive patients (p < 0.05) and in node-negative patients (p < 0.01). In
      conclusion, these results suggest that the immunoreactivity of p53 may be a
      biologic marker of prognostic significance in both node-positive and node
      negative patients.

PMID- 9580544
TI  - The safety of pyrimethamine and sulfadoxine for the prevention of Pneumocystis
      carinii pneumonia.
AB  - The medical records of 157 patients taking pyrimethamine-sulfadoxine for
      Pneumocystis carinii pneumonia prophylaxis were reviewed for assessment of safety
      and tolerance. 11 patients had experienced side effects, 7 (1 each: neutropenia,
      Stevens-Johnson, hepatic abnormalities; 2 each: subjective and hypersensitivity
      reactions) leading to a discontinuation of the drugs.

PMID- 9580545
TI  - Creptotrema agonostomi n. sp. (Trematoda: Allocreadiidae) from the intestine of
      freshwater fish of Mexico.
AB  - Creptotrema agonostomi n. sp. is described from the mugilid fish Agonostomus
      monticola from Rio Cuitzmala, Jalisco, east Mexico, from Rio Las Palmas and Rio
      Maquinas, Veracruz, west Mexico, and from the ictalurid, Ictalurus balsanus from
      Rio Chontalcoatlan, Guerrero, east Mexico. It is distinguished from other species
      of Creptotrema by its small size, large acetabulum with vertical incision, cirrus
      sac not reaching the posterior border of acetabulum, and very small eggs,
      measuring 0.041-0.057 x 0.020-0.033 mm.

PMID- 9580546
TI  - Factors related to the presence of IgA class antineutrophil cytoplasmic
      antibodies in ulcerative colitis.
AB  - OBJECTIVES: Few studies have assessed the IgA antineutrophil cytoplasmic antibody
      (ANCA) positivity in ulcerative colitis patients and there is no information
      about factors related to its synthesis and its status after colectomy. The aims
      of the study were to assess the serum IgA ANCA prevalence in ulcerative colitis
      patients, both nonoperated and operated, and to determine the clinical factors
      related to this positivity. METHODS: Fifty-four ulcerative colitis patients, 63
      ulcerative colitis colectomized patients (32 with Brooke's ileostomy and 31 with
      ileal pouch anal anastomosis), and 24 controls were studied. Antineutrophil
      cytoplasmic antibodies were detected by specific indirect immunofluorescent
      assays. RESULTS: The percentage of IgA ANCA was significantly higher in patients
      with ileal pouch anal anastomosis (45%) than in patients with Brooke's ileostomy
      (22%). There were no differences related to the presence of pouchitis in ileal
      pouch anal anastomosis patients. Patients with nonoperated extensive colitis
      (47%) had a significantly higher percentage of IgA ANCA than patients with
      proctitis (19%). Total percentage of ANCA (IgA and/or IgG) tended to be higher in
      ulcerative colitis and in patients with ileal pouch anal anastomosis than in
      patients with Brooke's ileostomy. However, in ileal pouch anal anastomosis
      patients, ANCA positivity was mainly due to exclusive IgA production.
      CONCLUSIONS: A substantial percentage of ulcerative colitis patients, and
      especially colectomized patients with ileal pouch anal anastomosis, had IgA ANCA,
      suggesting that ANCA production in ulcerative colitis might be stimulated by an
      immune reaction in the intestinal mucosa.

PMID- 9580547
TI  - Esophagitis dissecans superficialis (esophageal cast) complicating esophageal
      sclerotherapy.
AB  - Esophagitis dissecans superficialis is a rare and benign condition that involves
      the formation of an esophageal cast. This disorder has been described in
      association with a variety of etiologic factors. We report a case of an
      esophageal cast in a patient included in a program of sclerotherapy of varices.
      We discuss the possible relationship existing between sclerotherapy and the
      development of esophagitis dissecans superficialis.

PMID- 9580548
TI  - Malignant peripheral nerve sheath tumor in a water moccasin (Agkistrodon
      piscivorus).

PMID- 9580550
TI  - Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen
      removal.
AB  - Glutamine and glutamate transport activities were measured in isolated luminal
      and abluminal plasma membrane vesicles derived from bovine brain endothelial
      cells. Facilitative systems for glutamine and glutamate were almost exclusively
      located in luminal-enriched membranes. The facilitative glutamine carrier was
      neither sensitive to 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid inhibition
      nor did it participate in accelerated amino acid exchange; it therefore appeared
      to be distinct from the neutral amino acid transport system L1. Two Na-dependent
      glutamine transporters were found in abluminal-enriched membranes: systems A and
      N. System N accounted for approximately 80% of Na-dependent glutamine transport
      at 100 microM. Abluminal-enriched membranes showed Na-dependent glutamate
      transport activity. The presence of 1) Na-dependent carriers capable of pumping
      glutamine and glutamate from brain into endothelial cells, 2) glutaminase within
      endothelial cells to hydrolyze glutamine to glutamate and ammonia, and 3)
      facilitative carriers for glutamine and glutamate at the luminal membrane may
      provide a mechanism for removing nitrogen and nitrogen-rich amino acids from
      brain.

PMID- 9580549
TI  - Phospholipid interactions of a peptide from the fusion-related domain of the
      glycoprotein of VHSV, a fish rhabdovirus.
AB  - Previous studies mapped a p2 domain (aa 82-109) which binds phosphatidylserine
      (PS) (Estepa and Coll, 1996a) and contains three contiguous hydrophobic amino
      acid heptad repeats followed by a positively charged stretch (Coll, 1995b) in the
      glycoprotein G of the viral hemorrhagic septicemia virus (VHSV), a fish
      rhabdovirus. Anti-p2 antibodies inhibited low-pH VHSV-induced fusion (Estepa and
      Coll, 1997) and low-pH PS binding to VHSV (Estepa and Coll, 1996a). We report
      here further studies on the interaction of the synthetic peptide p2 with
      phospholipid vesicles. The synthetic p2 peptide was able to mediate aggregation,
      lipid mixing, and leakage of contents only with negatively charged phospholipid
      vesicles and in a concentration-dependent manner. As shown by its effect on lipid
      phase transitions deduced from data with fluorescence polarization and
      differential scanning calorimetry, the p2 peptide becomes inserted into the
      hydrophobic negatively charged phospholipid vesicle bilayers. In addition, data
      based on circular dichroism showed that the p2 peptide folds as a structure with
      a high content of beta-sheets stabilized by interaction with anionic
      phospholipids. These studies are potentially relevant to viral fusion in VHSV.

PMID- 9580551
TI  - Ultrasonographic appearance of an echinococcus ovarian cyst.
AB  - BACKGROUND: We describe the ultrasonographic pattern of a pelvic echinococcus
      cyst, visualized using a vaginal probe and color Doppler. CASE: A 27-year-old
      woman presented with an asymptomatic right adnexal mass. Vaginal ultrasonography
      revealed a cyst in the posterior cul-de-sac, adjacent to the right ovary, with
      internal septae resembling a maze or an onion slice structure. Color Doppler
      revealed peripheral vascularization with a low resistance pattern (resistance
      index 0.6; pulsatility index 0.93). Benign cysts usually have a simple echogenic
      pattern. In contrast, ovarian carcinomas have a complex internal structure.
      CONCLUSION: Ovarian echinococcus cysts may have a peculiar ultrasonographic
      pattern at high-frequency (7.5-MHz) vaginal ultrasonography. Such high-frequency
      ultrasonography can be a useful tool in the diagnosis of the disease.

PMID- 9580552
TI  - Dynamic activation of endothelial nitric oxide synthase by Hsp90.
AB  - Heat-shock protein 90 (Hsp90) coordinates the trafficking and regulation of
      diverse signalling proteins, but its precise role in regulating specific cellular
      targets is not known. Here we show that Hsp90 associates with endothelial nitric
      oxide synthase (eNOS) and is rapidly recruited to the eNOS complex by agonists
      that stimulate production of nitric oxide, namely vascular endothelial growth
      factor, histamine and fluid shear stress. Moreover, the binding of Hsp90 to eNOS
      enhances the activation of eNOS. Inhibition of signalling through Hsp90
      attenuates both agonist-stimulated production of nitric oxide and endothelium
      dependent relaxation of isolated blood vessels. Our results indicate that Hsp90
      facilitates signalling mediated by growth-factor, G-protein and
      mechanotransduction pathways that lead to the activation of eNOS. These
      observations indicate that in addition to its role as a molecular chaperone
      involved in protein folding and maturation, Hsp90 may also be recruited to
      cellular targets depending on the activation state of the cell.

PMID- 9580553
TI  - Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human
      endothelial cells: implications for atherogenesis.
AB  - To study the role of vascular cell adhesion molecule-1 (VCAM-1) in monocyte
      recruitment and atherogenesis, we constructed a recombinant adenovirus,
      AdRSVrVCAM-1, carrying the rabbit VCAM-1 cDNA. We have previously shown that
      AdRSVrVCAM-1-transduced human umbilical vein endothelial cells (HUVECs) support
      the adhesion of CD4+ CD45RO+ memory T lymphocytes under laminar flow conditions.
      We now demonstrate that AdRSVrVCAM-1-transduced HUVECs support the adhesion of
      peripheral blood monocytes at a shear stress of < or = 1.5 dyne/cm2. Although
      VCAM-1 supported only firm adhesion of lymphocytes, it was able to mediate
      monocyte rolling, firm adhesion, and transmigration when expressed in the context
      of otherwise unactivated vascular endothelium. VCAM-1-transduced HUVECs supported
      the adhesion of as many as 4-fold more monocytes than T cells under laminar flow.
      The greater monocyte adhesion was explained at least in part by leukocyte
      leukocyte interactions (secondary adhesions), which were not seen with T cells.
      These secondary monocyte interactions were specifically blocked by monoclonal
      antibodies to L-selectin and P-selectin glycoprotein ligand-1. These data
      demonstrate that VCAM-1 expressed in the context of unactivated vascular
      endothelium supports the adhesion of the leukocyte populations present in
      atherosclerotic plaque and may contribute to the predominance of monocytes over
      lymphocytes.

PMID- 9580554
TI  - Occupational asthma in the community: risk factors in a western Mediterranean
      population.
AB  - Risk factors and prevalence of occupational asthma in the general population were
      examined in a cross-sectional community study conducted in north Barcelona. A
      self-administered questionnaire that contained questions about bronchial asthma
      and occupation was mailed to a random sample of 4000 adults who lived in north
      Barcelona; the response rate was 31.0%. Investigators made phone calls to
      nonresponders to determine response bias. Risk factors for occupational asthma
      were assessed with logistic regression. Investigators, who sought a definite
      diagnosis of occupational asthma, offered a chest examination to all subjects who
      reported asthma in life and who experienced clinically relevant occupational
      exposures. The examination included skin tests to common allergens, forced
      spirometry with reversibility test, and peak expiratory flow rate at and away
      from work. Cumulative prevalences obtained from responders were good estimates
      for the general population: asthma in life, 9.0%; clinically relevant
      occupational exposure, 28.9%; and respiratory symptoms at work, 18.3%.
      Adjustments were made for age, sex, and smoking habits, and relevant exposure
      caused an increase in asthma risk (odds ratio [OR] = 1.9; 95% confidence interval
      [95% CI] = 1.1, 3.2); however, when investigators introduced specific occupations
      in the model as independent variables, only occupational exposure to leather (OR
      = 12.8 [95% CI = 4.4, 37.4]), animals (OR = 10.3 [95% CI = 1.6, 65.2]), dyes (OR
      = 5.6 [95% CI = 2.1, 15.3]), and flour (OR = 4.6 [CI = 1.3, 15.7]) persisted as
      significant risk factors. A 1.7/1000 minimum prevalence of occupational asthma
      for the north Barcelona population was estimated from chest examination results.
      Occupational risk for asthma appeared to be associated with exposure to leather,
      animals, dyes, or flour in the north Barcelona area.

PMID- 9580555
TI  - The parasitophorous vacuole membrane surrounding Plasmodium and Toxoplasma: an
      unusual compartment in infected cells.
AB  - Plasmodium and Toxoplasma belong to a group of unicellular parasites which
      actively penetrate their respective mammalian host cells. During the process of
      invasion, they initiate the formation of a membrane, the so-called
      parasitophorous vacuolar membrane, which surrounds the intracellular parasite and
      which differs substantially from endosomal membranes or the membrane of
      phagolysosomes. The biogenesis and the maintenance of the vacuolar membrane are
      closely related to the peculiar cellular organization of these parasites and are
      unique phenomena in cell biology. Here we compare biological similarities and
      differences between the two parasites, with respect to: (i) the formation, (ii)
      the maintenance, and (iii) the biological role of the vacuolar membrane. We
      conclude that most differences between the organisms primarily reflect the
      different biosynthetic capacities of the host cells they invade.

PMID- 9580556
TI  - Focusing on spindle poles.
AB  - Spindle poles are discernible by light microscopy as the sites where microtubules
      converge at the ends of both mitotic and meiotic spindles. In most cell types
      centrosomes are present at spindle poles due to their dominant role in
      microtubule nucleation. However, in some specialized cell types microtubules
      converge into spindle poles in the absence of centrosomes. Thus, spindle poles in
      centrosomal and acentrosomal cell types are structurally different, and it is
      this structural dichotomy that has created confusion as to the mechanism by which
      microtubules are organized into spindle poles. This review summarizes a series of
      recent articles that begin to resolve this confusion by demonstrating that
      spindle poles are organized through a common mechanism by a conserved group of
      non-centrosomal proteins in the presence or absence of centrosomes.

PMID- 9580557
TI  - BDNF-GFP containing secretory granules are localized in the vicinity of synaptic
      junctions of cultured cortical neurons.
AB  - The protein family of mammalian neurotrophins, comprising nerve-growth factor
      (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 and -4/5 (NT-3,
      NT-4/5), supports the survival and the phenotype of neurons from the central as
      well as the peripheral nervous system (CNS, PNS). In addition, exogenous
      application of neurotrophins has recently been found to modulate synaptic
      transmission in the rodent CNS. However, to provide evidence for a role of
      neurotophins as endogenous fast acting modulators of synaptic transmission, the
      synaptic localization and secretion of neurotrophins needs to be shown. We have
      now constructed a fusion protein consisting of N-terminal BDNF (the most abundant
      neurotrophin in the rodent hippocampus and neocortex) and C-terminal green
      fluorescent protein (GFP) to elucidate the cellular localization of BDNF in
      cortical neurons. Transient expression of BDNF-GFP in COS-7 cells revealed that
      the cellular localization in the trans-Golgi network (TGN), the processing of
      precursor proteins and the secretion of mature BDNF-GFP is indistinguishable from
      the properties of untagged BDNF. Upon transient transfection of primary rat
      cortical neurons, BDNF-GFP was found in secretory granules of the regulated
      pathway of secretion, as indicated by colocalization with the secretory granule
      marker secretogranin II. BDNF-GFP vesicles were found in the neurites of
      transfected neurons with a pattern reminiscent of the localization of endogenous
      BDNF in untransfected cortical neurons. BDNF-GFP vesicles were found
      predominantly in the somatodendritic compartment of the neurons, whereas
      additional axonal localization was found less frequently. Immunocytochemical
      staining of synaptic terminals with synapsin I antibodies revealed that the
      density of BDNF-GFP vesicles is elevated in the vicinity of synaptic junctions,
      indicating that BDNF is localized appropriately to function as an acute modulator
      of synaptic transmission. These data suggest that BDNF-GFP will be a useful tool
      to investigate synaptic release of BDNF during physiological synaptic
      stimulation, and will thereby allow us to elucidate the participation of
      neurotrophin release in activity dependent synaptic plasticity.

PMID- 9580558
TI  - The RNP protein, RNPS1, associates with specific isoforms of the p34cdc2-related
      PITSLRE protein kinase in vivo.
AB  - The PITSLRE protein kinases are members of the p34cdc2 superfamily, with >20
      different isoforms expressed from two linked genes in humans. PITSLRE homologues
      have been identified in mouse, chicken, Drosophila, Xenopus, and possibly
      Plasmodium falciparum, suggesting that their function may be well conserved. A
      possible role for a caspase processed PITSLRE isoform has been suggested by
      studies of Fas- and TNF-induced cell death. However, the function of these
      kinases in proliferating cells is still unknown. Here we demonstrate that the 110
      kDa PITSLRE isoforms (p110) are localized to both the nucleoplasm and nuclear
      speckles, and that these isoforms specifically interact in vitro and in vivo with
      the RNA-binding protein RNPS1. RNPS1 is also localized to nuclear speckles, and
      its over expression disrupts normal nuclear speckle organization by causing the
      aggregation of many nuclear speckles into approximately 6 'mega' speckles. This
      type of nuclear speckle aggregation closely resembles what occurs when cells are
      treated with several transcriptional inhibitors. These data indicate that the
      PITSLRE p110 isoforms interact with RNPS1 in vivo, and that these proteins may in
      turn influence some aspect of transcriptional and/or splicing regulation.

PMID- 9580559
TI  - Recycling of the yeast v-SNARE Sec22p involves COPI-proteins and the ER
      transmembrane proteins Ufe1p and Sec20p.
AB  - Vesicle-specific SNAP receptors (v-SNAREs) are believed to cycle between
      consecutive membrane compartments. The v-SNARE Sec22(Sly2)p mediates the
      targeting of vesicles between endoplasmic reticulum (ER) and early Golgi of
      Saccharomyces cerevisiae. To analyze factors involved in targeting of
      Sec22(Sly2)p, an alpha-factor-tagged Sec22 protein (Sec22-alpha) was employed.
      Only on reaching the late Golgi, can alpha-factor be cleaved from this hybrid
      protein by Kex2p, a protease localized in this compartment. In wild-type cells
      Kex2p-cleavage is observed only when Sec22-alpha is greatly overproduced.
      Immunofluorescence microscopy and subcellular fractionation studies showed that
      Sec22-alpha is returned to the ER from the late Golgi (Kex2p) compartment. When
      Sec22-alpha is expressed in wild-type cells at levels comparable to the
      quantities of endogenous Sec22p, very little of this protein is cleaved by Kex2p.
      Efficient cleavage, however, occurs in mutants defective in the retrograde
      transport of different ER-resident proteins indicating that Sec22-alpha rapidly
      reaches the late Golgi of these cells. These mutants (sec20-1, sec21-1, sec27-1
      and ufe1-1) reveal Golgi structures when stained for Sec22-alpha and do not show
      the ER-immunofluorescence observed in wild-type cells. These results show
      consistently that Sec22p recycles from the Golgi back to the ER and that this
      recycling involves retrograde COPI vesicles.

PMID- 9580560
TI  - The expression of an Ets1 transcription factor lacking its activation domain
      decreases uPA proteolytic activity and cell motility, and impairs normal
      tubulogenesis and cancerous scattering in mammary epithelial cells.
AB  - Cell migration and invasion play a crucial role during normal and pathological
      development. The expression of several members of the Ets family of transcription
      factors has been shown to correlate with the occurrence of these processes. In
      the present study, we investigated the effect of the expression of Ets1-DB, the
      DNA-binding domain of c-Ets1, on the functional properties of NMuMG and MMT
      epithelial cell lines, from normal and cancerous mouse mammary tissues,
      respectively. We found that stable expression of this Ets1-DB mutant inhibited,
      in both cell types, the gene expression and activity of urokinase type
      plasminogen activator (uPA), a potential target of c-Ets1. uPA is a key serine
      proteinase in the proteolytic cascade leading to the degradation of the
      extracellular matrix. In two-dimensional cultures, expression of the Ets1-DB
      mutant resulted in a decrease in cell migration and invasion in both cell lines.
      In three-dimensional collagen gels, NMuMG cells underwent tubular morphogenesis,
      while MMT cells developed as scattered structures. The Ets1-DB mutant impaired
      the capacity of NMuMG cells to form tubules and reduced the ability of MMT cells
      to invade these gels. Similar inhibition of cell migration, invasion and
      morphogenesis were observed in non-infected NMuMG and MMT cell lines treated with
      aprotinin, a serine proteinase inhibitor, suggesting that the inhibition of the
      plasmin cascade mediates in part the biological effects induced by the Ets1-DB
      mutant. These results demonstrate that Ets family members are involved in the
      control of uPA activity, cell motility and invasion during normal tubular
      morphogenesis and cancerous scattering in mammary epithelial cells.

PMID- 9580561
TI  - Rescue of the mutant phenotype by reexpression of full-length vinculin in null F9
      cells; effects on cell locomotion by domain deleted vinculin.
AB  - Vinculin plays a role in signaling between integrins and the actin cytoskeleton.
      We reported earlier that F9-derived cells lacking vinculin are less spread, less
      adhesive, and move two times faster than wild-type F9 cells. Expression of intact
      vinculin in null cells restored all wild-type characteristics. In contrast,
      expression of the head (90 kDa) fragment exaggerated mutant characteristics,
      especially locomotion, which was double that of vinculin null cells. Expression
      of the tail domain also had a marked effect on locomotion in the opposite
      direction, reducing it to very low levels. The expression of the head plus tail
      domains together (no covalent attachment) effected a partial rescue towards wild
      type phenotype, thus indicating that reexpressed polypeptides may be in their
      correct location and are interacting normally. Therefore, we conclude that: (1)
      the head domain is part of the locomotory force of the cell, modulated by the
      tail, and driven by the integrin/matrix connection; (2) intact vinculin is
      required for normal regulation of cell behavior, suggesting that vinculin head
      tail interactions control cell adhesion, spreading, lamellipodia formation and
      locomotion.

PMID- 9580562
TI  - Spinalin, a new glycine- and histidine-rich protein in spines of Hydra
      nematocysts.
AB  - Here we present the cloning, expression and immunocytochemical localization of a
      novel 24 kDa protein, designated spinalin, which is present in the spines and
      operculum of Hydra nematocysts. Spinalin cDNA clones were identified by in situ
      hybridization to differentiating nematocytes. Sequencing of a full-length clone
      revealed the presence of an N-terminal signal peptide, suggesting that the mature
      protein is sorted via the endoplasmic reticulum to the post-Golgi vacuole in
      which the nematocyst is formed. The N-terminal region of spinalin (154 residues)
      is very rich in glycines (48 residues) and histidines (33 residues). A central
      region of 35 residues contains 19 glycines, occurring mainly as pairs. For both
      regions a polyglycine-like structure is likely and this may be stabilized by
      hydrogen bond-mediated chain association. Similar sequences found in loricrins,
      cytokeratins and avian keratins are postulated to participate in formation of
      supramolecular structures. Spinalin is terminated by a basic region (6 lysines
      out of 15 residues) and an acidic region (9 glutamates and 9 aspartates out of 32
      residues). Western blot analysis with a polyclonal antibody generated against a
      recombinant 19 kDa fragment of spinalin showed that spinalin is localized in
      nematocysts. Following dissociation of the nematocyst's capsule wall with DTT,
      spinalin was found in the insoluble fraction containing spines and the operculum.
      Immunocytochemical analysis of developing nematocysts revealed that spinalin
      first appears in the matrix but then is transferred through the capsule wall at
      the end of morphogenesis to form spines on the external surface of the inverted
      tubule and the operculum.

PMID- 9580563
TI  - Role of fungal dynein in hyphal growth, microtubule organization, spindle pole
      body motility and nuclear migration.
AB  - Cytoplasmic dynein is a microtubule-associated motor protein with several
      putative subcellular functions. Sequencing of the gene (DHC1) for cytoplasmic
      dynein heavy chain of the filamentous ascomycete, Nectria haematococca, revealed
      a 4,349-codon open reading frame (interrupted by two introns) with four highly
      conserved P-loop motifs, typical of cytoplasmic dynein heavy chains. The
      predicted amino acid sequence is 78.0% identical to the cytoplasmic dynein heavy
      chain of Neurospora crassa, 70.2% identical to that of Aspergillus nidulans and
      24.8% identical to that of Saccharomyces cerevisiae. The genomic copy of DHC1 in
      N. haematococca wild-type strain T213 was disrupted by inserting a selectable
      marker into the central motor domain. Mutants grew at 33% of the wild-type rate,
      forming dense compact colonies composed of spiral and highly branched hyphae.
      Major cytological phenotypes included (1) absence of aster-like arrays of
      cytoplasmic microtubules focused at the spindle pole bodies of post-mitotic and
      interphase nuclei, (2) limited post-mitotic nuclear migration, (3) lack of
      spindle pole body motility at interphase, (4) failure of spindle pole bodies to
      anchor interphase nuclei, (5) nonuniform distribution of interphase nuclei and
      (6) small or ephemeral Spitzenkorper at the apices of hyphal tip cells.
      Microtubule distribution in the apical region of tip cells of the mutant was
      essentially normal. The nonuniform distribution of nuclei in hyphae resulted
      primarily from a lack of both post-mitotic nuclear migration and anchoring of
      interphase nuclei by the spindle pole bodies. The results support the hypothesis
      that DHC1 is required for the motility and functions of spindle pole bodies,
      normal secretory vesicle transport to the hyphal apex and normal hyphal tip cell
      morphogenesis.

PMID- 9580565
TI  - Transient ER retention as stress response: conformational repair of heat-damaged
      proteins to secretion-competent structures.
AB  - Mechanisms to acquire tolerance against heat, an important environmental stress
      condition, have evolved in all organisms, but are largely unknown. When
      Saccharomyces cerevisiae cells are pre-conditioned at 37 degrees C, they survive
      an otherwise lethal exposure to 48-50 degrees C, and form colonies at 24 degrees
      C. We show here that incubation of yeast cells at 48-50 degrees C, after pre
      conditioning at 37 degrees C, resulted in inactivation of exocytosis, and in
      conformational damage and loss of transport competence of proteins residing in
      the endoplasmic reticulum (ER). Soon after return of the cells to 24 degrees C,
      membrane traffic was resumed, but cell wall invertase, vacuolar carboxypeptidase
      Y and a secretory beta-lactamase fusion protein remained in the ER for different
      times. Thereafter their transport competence was resumed very slowly with widely
      varying kinetics. While the proteins were undergoing conformational repair in the
      ER, their native counterparts, synthesized after shift of the cells to 24 degrees
      C, folded normally, by-passed the heat-affected copies and exited rapidly the ER.
      The Hsp70 homolog Lhs1p was required for acquisition of secretion competence of
      heat-damaged proteins. ER retention and refolding of heat-denatured glycoproteins
      appear to be part of the cellular stress response.

PMID- 9580564
TI  - Characterizing titin's I-band Ig domain region as an entropic spring.
AB  - The poly-immunoglobulin domain region of titin, located within the elastic
      section of this giant muscle protein, determines the extensibility of relaxed
      myofibrils mainly at shorter physiological lengths. To elucidate this region's
      contribution to titin elasticity, we measured the elastic properties of the N
      terminal I-band Ig region by using immunofluorescence/immunoelectron microscopy
      and myofibril mechanics and tried to simulate the results with a model of
      entropic polymer elasticity. Rat psoas myofibrils were stained with titin
      specific antibodies flanking the Ig region at the N terminus and C terminus,
      respectively, to record the extension behaviour of that titin segment. The
      segment's end-to-end length increased mainly at small stretch, reaching
      approximately 90% of the native contour length of the Ig region at a sarcomere
      length of 2.8 microm. At this extension, the average force per single titin
      molecule, deduced from the steady-state passive length-tension relation of
      myofibrils, was approximately 5 or 2.5 pN, depending on whether we assumed a
      number of 3 or 6 titins per half thick filament. When the force-extension curve
      constructed for the Ig region was simulated by the wormlike chain model, best
      fits were obtained for a persistence length, a measure of the chain's bending
      rigidity, of 21 or 42 nm (for 3 or 6 titins/half thick filament), which correctly
      reproduced the curve for sarcomere lengths up to 3.4 microm. Systematic
      deviations between data and fits above that length indicated that forces of >30
      pN per titin strand may induce unfolding of Ig modules. We conclude that
      stretches of at least 5-6 Ig domains, perhaps coinciding with known super repeat
      patterns of these titin modules in the I-band, may represent the unitary lengths
      of the wormlike chain. The poly-Ig regions might thus act as compliant entropic
      springs that determine the minute levels of passive tension at low extensions of
      a muscle fiber.

PMID- 9580566
TI  - GTPgammaS-induced actin polymerisation in vitro: ATP- and phosphoinositide
      independent signalling via Rho-family proteins and a plasma membrane-associated
      guanine nucleotide exchange factor.
AB  - In a cell-free system from neutrophil cytosol GTP(&ggr ;)S can induce an increase
      in the number of free filament barbed ends and massive actin polymerisation and
      cross-linking. GTP(&ggr ;)S stimulation was susceptible to an excess of GDP, but
      not Bordetella pertussis toxin and could not be mimicked by aluminium fluoride,
      myristoylated GTPgammaS.Gialpha2 or Gbeta1gamma2 subunits of trimeric G proteins.
      In contrast, RhoGDI and Clostridium difficile toxin B (inactivating Rho family
      proteins) completely abrogated the effect of GTPgammaS. When recombinant,
      constitutively activated and GTPgammaS-loaded Rac1, RhoA, or Cdc42 proteins alone
      or in combination were probed at concentrations >100 times the endogenous,
      however, they were ineffective. Purified Cdc42/Rac-interactive binding (CRIB)
      domain of WASP or C3 transferase did not prevent actin polymerisation by
      GTPgammaS. The action of GTPgammaS was blocked by mM [Mg2+], unless a heat- and
      trypsin-sensitive component present in neutrophil plasma membrane was added.
      Liberation of barbed ends seems therefore to be mediated by a toxin B-sensitive
      cytosolic Rho-family protein, requiring a membrane-associated guanine nucleotide
      exchange factor (GEF) for its activation by GTPgammaS under physiologic
      conditions. The inefficiency of various protein kinase and phosphatase inhibitors
      (staurosporine, genistein, wortmannin, okadaic acid and vanadate) and removal of
      ATP by apyrase, suggests that phosphate transfer reactions are not required for
      the downstream propagation of the GTPgammaS signal. Moreover, exogenously added
      phosphoinositides failed to induce actin polymerisation and a PtdIns(4,5)P2
      binding peptide did not interfere with the response to GTPgammaS. The speed and
      simplicity of the presented assay applicable to protein purification techniques
      will facilitate the further elucidation of the molecular partners involved in
      actin polymerisation.

PMID- 9580567
TI  - Hyaluronan-dependent cell migration can be blocked by a CD44 cytoplasmic domain
      peptide containing a phosphoserine at position 325.
AB  - CD44 is the principle transmembrane receptor for the extracellular matrix
      glycosaminoglycan hyaluronan. This receptor:ligand interaction plays an essential
      role in a number of physiological events including tumour progression, lymphocyte
      homing into inflammatory sites and tissue morphogenesis during development. In
      previous studies we have shown that serine phosphorylation is a critical control
      mechanism for CD44-dependent cell migration. Here we have investigated the target
      phosphorylation residues by mutating them individually or in combination. These
      studies demonstrate that Ser325 is the principle CD44 phosphorylation site and
      that mutation of this residue blocks CD44-mediated cell migration but not
      hyaluronan binding. In addition, we show that an upstream Ser323 residue is
      required as part of the kinase consensus site. To further characterize the role
      of CD44 phosphorylation, phosphorylated and non-phosphorylated peptides spanning
      the Ser325 region were synthesised and linked to a 16 amino acid Penetratin
      sequence to mediate efficient plasma membrane translocation. Peptides containing
      a phosphoserine at residue 325 are efficient blockers of CD44-mediated cell
      migration but do not reduce CD44 expression or its ability to bind hyaluronan.
      These data strongly argue that CD44 adhesion and migration are regulated by
      distinct mechanisms and that migration requires the specific interaction of
      intracellular component(s) with phosphorylated CD44 receptors.

PMID- 9580568
TI  - In vitro cytopathogenicity of the human immunodeficiency virus (HIV)-1 predicts
      survival in HIV-infected hemophiliacs independent from CD4 cell count.
AB  - In addition to quantification of viral load the graded cytopathogenicity of the
      human immunodeficiency virus may provide prognostic information for the course of
      HIV infection. However, the prognostic value of graded cytopathogenicity in
      addition to the CD4 count has not been evaluated in a large longitudinal study.
      Therefore a total of 216 HIV-seropositive hemophiliacs have been followed up from
      1985 to 1998 (mean follow-up 70.4 +/- SD 26 months, median 72, range: 12 to 120
      months). In vitro virulence was determined according to cytopathic effects on
      freshly isolated PBMC of healthy donors and graded from A (strongest
      cytopathogenic effect) to D (no cytopathic isolate effect). Survival was analyzed
      among patients with different virus isolates by Kaplan-Meier statistics (log
      rank) and factors independently associated with decreased survival were analyzed
      by Cox hazard regression analysis. - A virus isolate A was found in 22 (10.2%)
      patients, a virus isolate B was found in 21 (9.3%) patients, a virus isolate C
      was found in 9 (4.2%) and a virus isolate D was found in 10 (4.2%) patients. Mean
      survival times were 48 months (95% Confidence Interval (CI) = 36 - 60) in
      patients with isolate A, 72 months (CI = 36 - 108) with isolate B, 84 months (CI
      = 48-120) with isolate C, 72 months (60 - 96) with isolate D and 96 months (CI =
      96 - 108) in patients with a negative virus culture (p < 0.001). Cox regression
      analysis indicated significant associations with outcome for young age (p
      <0.001), positive virus culture (p < 0.0001) and CD4 count (p < 0.0001) as
      independent predictors of survival. The presence of an isolate A revealed the
      strongest odds ratio (6.3, 95% CI 2.9-13.2). Our data indicate that the presence
      of a virus isolate A represents a strong risk factor for mortality in the course
      of HIV infection. Besides quantification of viral load and CD4 count, the graded
      cytopathogenicity may provide additional information for early and aggressive
      antiretroviral treatment, since the mean survival in patients with cytopathogenic
      virus isolates is reduced significantly.

PMID- 9580569
TI  - Influence of positive end-expiratory pressure ventilation (PEEP) on left
      ventricular pattern of contraction in experimental ARDS.
AB  - The aim of the present study was to investigate the pattern of ventricular
      dynamic contraction and its relation to changes of transseptal pressure gradient
      during ventilation with positive end-expiratory pressure (PEEP). For that
      purpose, left (LV) and right ventricular (RV) pressures as well as ventricular
      shortening in septal-lateral (s.l.) direction were assessed in 8 dogs (RV n = 5)
      exposed to experimental acute respiratory distress syndrome (eARDS) and PEEP 10
      and 20 cmH2O (P10, P20). Despite maintenance of transmural central venous
      pressure by volume substitution, PEEP resulted in a fall of stroke index (P10 vs.
      eARDS: -7%, p<0.05; P20 vs. P10: -28%, p<0.05); this was accompanied by a fall of
      LV end-diastolic diameter (P10 vs. eARDS: -3.1%, p<0.01; P20 vs. P10: -7.4%,
      p<0.01). Although the transseptal LV to RV end- diastolic pressure gradient
      changed only minimally, there was a significant increase of paradoxic left
      ventricular systolic lengthening from 3.1% at eARDS to 4.5% at P10 (p<0.05 vs.
      eARDS) and 8.4% at P20 (p<0.05 vs. P10). Neither RV end-diastolic diameter nor
      s.l. shortening were significantly influenced by P10 or P20. It is concluded,
      that a rearrangement of LV dynamic contraction does occur during ventilation with
      PEEP, which is compatible with the concept of paradoxic systolic bulging of the
      interventricular septum towards the lumen of the right ventricle. Since this
      phenomenon occurred independent from changes of the end-diastolic pressure
      gradient between both ventricles, we suggest that systolic septal movement to the
      right is an active contractile process to support the function of a stressed RV.

PMID- 9580570
TI  - Attenuation of the near-infrared and red photoplethysmographic signal by
      different depth of tissues.
AB  - Photoplethysmography enables non-invasive investigation of the volume pulse in
      the microvasculature of patients. We previously have shown that time-discrete
      analysis enables identification of highly reproducible characteristics of the
      volume pulse in absolute values. The method would be of particular interest, if
      the perfusion of deeper tissue layers like the skeletal muscle can be assessed.
      The aim of the current study was to investigate the attenuation of the
      photoplethysmographic signal by different tissues and up to which depth of tissue
      a time-discrete analysis of the photoplethysmographic signal would be possible.
      For the recordings we used the time-discrete near-infra-red photoplethysmography
      (NIRP), a reflection photoplethysmograph measuring at wavelengths of 840 nm and
      640 nm. In an in vitro circuit filled with bovine blood we generated a typical
      and exactly reproducible volume pulse. On a platform the NIRP sensor probe was
      placed above the artificial vessel and recordings of the volume pulse were
      obtained by varying the sensor-vessel-distance with increasing layers of water,
      blood-agar or bovine skeletal muscle tissue. - The amplitude of the NIR signal
      was attenuated to 50% by each layer of 2.01 mm of water, 1.42 mm of blood-agar
      and 1.05 mm of bovine skeletal muscle tissue. A time-discrete analysis could be
      performed up to a depth of 15 mm of water, 6 mm of blood-agar and 5 mm of bovine
      skeletal muscle tissue. - As the photoplethysmographic curve is strongly
      attenuated even by a few millimetres of water we suggest that the NIRP signal
      mirrors the perfusion of the superficial tissue layer and mainly originates from
      the subpapillary capacious plexus. - We conclude that with the equipment used in
      this study volume pulsations in deeper layers of tissue like skeletal musculature
      can not be assessed.

PMID- 9580571
TI  - Changes in the arteriolar volume pulse of the finger during various degrees of
      tilt using near infra-red and red photoplethysmography.
AB  - 1. Photoplethysmography is a widely used non invasive technique for the
      measurement of peripheral oxygen saturation. A more detailed analysis of the
      volume pulse (VP) can indicate alterations in peripheral vascular tone, due to
      sympathetic stimulation, stress, pain and temperature. - 2. In six healthy male
      volunteers we investigated changes in the VP resulting from vasoconstriction and
      vasodilatation induced by varies degrees of tilt. Subjects were subjected 0
      degrees tilt followed by head down -8 degrees -15 degrees, -30 degrees -15
      degrees, -8 degrees, 0 degrees, 15 degrees, 30 degrees , 70 degrees, 30 degrees,
      15 degrees and 0 degrees. Each tilt stage was sustained for 15 minutes. Both VP -
      and haemodynamic changes were continuously recorded 30s before and then for 210 s
      after the imposition of each tilt step. We used a new computer driven soft and
      hardware for the analysis of the VP. 3. The VP signal was obtained with a sensor
      emitting 840 nm (NIR) and 640 nm (RED) light into finger tip with a sample rate
      of 128 Hz. All data was normalised to the initial mean value obtained at 0
      degrees tilt. The signal strength parameters amplitude, and area under the curve
      and the first derivative of the amplitude (flux) as well as time discrete
      parameters, time of first maximum (Tmax), dicrote wave (Td), volume pulse
      decrease (Tdec) and fundamental arterial oscillation Tag = Td - Tmax were
      measured. 4. HR increased significantly during 30 degrees and 70 degrees tilt,
      but no change in the other hemodynamic parameters was observed. Amplitude, area
      under the curve and flux of both the Red and the NIR signal increased following
      head down tilt. A significant decrease of those parameters was found during foot
      down tilt. 5. No significant changes were found in the time discrete values,
      neither within each tilt step nor when compared to the initial mean value at 0
      degrees tilt. 6. This study reveals that signal strength related parameters such
      as area under the curve, amplitude and flux reflect changes in vascular tone.
      Time discrete parameters however did not depict these changes and appear
      unsuitable for data analysis when using this specific hardware applied in the
      current study.

PMID- 9580572
TI  - Modulation of cystic fibrosis transmembrane conductance regulator gene -
      expression by elevation of intracellular cyclic AMP.
AB  - Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. Its product is a cyclic AMP-dependent Cl-
      channel, that is defective in CF. Since cAMP regulates the expression of many
      genes and since the 5'-flanking region of the CFTR gene contains cAMP response
      elements, we hypothesized that intracellular cAMP might modulate not only the
      cAMP-dependent Cl- channel CFTR, but also CFTR gene expression in epithelial
      cells. To accomplish this, we investigated Cl- secretion and CFTR-mRNA levels in
      HT-29 and T84 colon carcinoma epithelial cells before and after exposure to
      forskolin and 8-bromo-cAMP for 12 hr. While resting T84 cells increased Cl-
      secretion in response to forskolin strongly and immediately, HT-29 cells did not,
      although both cell lines showed highly increased Cl- efflux in response to
      A23187, a calcium ionophore. Interestingly, prolonged exposure to forskolin (12
      hr) induced a clear decrease of CFTR-mRNA levels in T84 cells, but an increase of
      CFTR-mRNA levels in HT-29 cells, thus demonstrating different behaviour of CFTR
      gene regulation in different epithelial cells in response to intracellular cAMP.
      These results suggest that cells with an effective cAMP-dependent Cl- channel
      (CFTR) respond to prolonged stimulation of this channel with down-regulation of
      CFTR gene expression, while cells with no effective cAMP-dependent Cl--secretion
      respond with an up-regulation of CFTR gene expression.

PMID- 9580573
TI  - Pituitary apoplexy manifested by sterile meningitis.
AB  - Pituitary apoplexy is rare and underdiagnosed. It results from either infarction
      or hemorrhage into an adenoma of the pituitary gland. The clinical presentation
      comprises a rapid development of impaired consciousness, severe headache, and
      amblyopia or diplopia. Meningeal irritation signs are considered rare and have
      not been reported as presenting signs. We report a 64-year-old patient whose
      presentation with necrosis of a pituitary adenoma was clinically
      indistinguishable from infectious meningitis.

PMID- 9580574
TI  - Asymptomatic pneumatosis intestinalis and free abdominal air in a patient with
      AIDS.
AB  - Detection of free abdominal air requires in most cases immediate surgical
      intervention. However, there may be situations, where invasive procedures are not
      indicated. We present a case of asymptomatic pneumatosis intestinalis and free
      abdominal air in a patient with Aids. Pneumatosis intestinalis is a rare entity
      with accumulation of subserosal or submucosal gas occurring in the small or large
      bowel. It has been reported in a variety of gastrointestinal disorders, in Aids,
      after transplantation, with steroid use, and in association with leukemia,
      lymphoma, vasculitis, collagen vascular disease and chronic obstructive pulmonary
      disease.

PMID- 9580575
TI  - Dose-response analysis of opioid cross-tolerance and withdrawal suppression
      during LAAM maintenance.
AB  - Levo-alpha-acetylmethadol (LAAM) currently is approved as an opioid maintenance
      treatment. This double-blind study was designed to characterize withdrawal
      suppression and opioid blockade produced by two different LAAM maintenance doses.
      Outpatient opioid-dependent volunteers were stabilized (5-7 weeks) on 25 (n = 8)
      or 75 mg (n = 8) LAAM administered every-other-day with placebo administered on
      intervening days. After stabilization, four inpatient, randomly ordered
      experimental sessions were conducted at 24, 48, 72 and 96 hr after LAAM dosing;
      the timing of these sessions corresponds to intervals that occur during typical
      thrice-weekly treatment and after a missed dose. During each session, after
      baseline assessments, ascending doses of hydromorphone (0, 6 and 12 mg i.m.) were
      administered 45 min apart; physiological, subjective and observer-rated effects
      were recorded throughout the session. Physiological and subjective indices of
      opioid withdrawal measured at session base lines increased with time since the
      last LAAM dose, but did not depend on the maintenance dose. Withdrawal symptoms
      were mild in both groups, even at 96 hr after LAAM dosing. Hydromorphone produced
      dose-related opioid agonist effects at all intervals in the 25 mg LAAM group;
      these effects were attenuated substantially in the 75 mg LAAM group. Time since
      last LAAM dose had little influence on hydromorphone effects in either group.
      Thus, 75 mg LAAM provides opioid blockade and withdrawal suppression for up to 96
      hr, whereas 25 mg LAAM is relatively ineffective at producing significant opioid
      blockade.

PMID- 9580576
TI  - Preclinical evaluation of PNU-151774E as a novel anticonvulsant.
AB  - PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide,
      methanesulfonate] is a structurally novel anticonvulsant having Na+ channel
      blocking and glutamate release-inhibiting properties, as well as being a MAOB
      inhibitor. Its anticonvulsant activity was evaluated in the maximal electroshock
      (MES) test and in chemically induced seizures (bicuculline, BIC; picrotoxin, PIC;
      3-mercaptopropionic acid, 3-MPA; pentylenetetrazole, PTZ; strychnine, STRYC).
      Behavioral toxicity was evaluated in the rotorod test with measurements of
      spontaneous locomotor activity and passive avoidance responding. The anti-MES
      activity of PNU-151774E in both mice and rats, respectively, produced ED50 values
      of 4.1 mg/kg and 6.9 mg/kg after i.p. administration or 8.0 mg/kg and 11.8 mg/kg
      after p.o. administration. Oral anti-MES activity in rats peaked between 1 and 2
      h after administration and was evident up to 4 h. This activity was related to
      brain levels of unchanged drug which peaked at 37 mM within 1 h. Oral ED50 values
      (mg/kg) effective in blocking tonic extension seizures by chemical convulsants in
      mice were: BIC (26.9), PIC (60.6), 3-MPA (21.5), STRYC (104.1) and PTZ (26.8).
      This potency was associated with high therapeutic indices relative to: MES
      (78.2), BIC (23.3), PIC (10.3), 3-MPA (29.1) and STRYC (6.0). No evidence of
      tolerance to anti-MES activity after repeated dosing was observed. PNU-151774E
      did not show anti-absence seizure activity as assessed by i.v. infusion of PTZ.
      PNU-151774E impaired spontaneous activity in rats only at the oral rotorod ED50
      dose of 700 mg/kg p.o. PNU-151774E did not impair passive avoidance responding at
      doses up to 40 times the oral MES ED50 dose in rats. These results indicate that
      PNU-151774E is an anticonvulsant effective in various seizure models with a wide
      therapeutic window, and with a low potential to induce tolerance and locomotor or
      cognitive side effects.

PMID- 9580577
TI  - Electrophysiological characterization of the effect of long-term duloxetine
      administration on the rat serotonergic and noradrenergic systems.
AB  - Duloxetine is a dual serotonin (5-HT)/norepinephrine (NE) re-uptake blocker with
      antidepressant potential. In the present in vivo electrophysiological study, the
      changes in the function of the rat 5-HT and NE systems after 2- and 21-day
      administration of duloxetine (20 mg/kg/day) were assessed in the dorsal
      hippocampus and the dorsal raphe nucleus (DRN). The firing rate of DRN neurons
      was decreased after 2 days of duloxetine, but returned to the control level after
      21-day administration. This recovery of firing rate was presumably due to the
      desensitization of the DRN somatodendritic 5-HT1A autoreceptors found after long
      term duloxetine administration. Overall serotonergic tone was assessed by
      examining the ability of the 5-HT1A antagonist WAY 100635 to alter hippocampal
      firing. WAY 100635 increased hippocampal firing rates in 21-day treated rats to a
      greater extent than in 2-day treated or control rats, suggesting that long-term
      administration induced an increase in endogenous levels of 5-HT in postsynaptic
      regions. This increase in 5-HT levels was accompanied by selective changes in the
      5-HT and NE systems induced by long-term duloxetine administration, i.e., the
      desensitization of the alpha-2 adrenergic heteroreceptor on 5-HT terminals and
      the continued blockade of the 5-HT transporters. In contrast, the sensitivity of
      the alpha-2 adrenergic and terminal 5-HT1B autoreceptors, as well as that of the
      postsynaptic 5-HT1A receptor after 21-day treatment was unchanged. Therefore,
      this study demonstrates that duloxetine increases serotonergic tone in a limbic
      forebrain structure and may therefore be effective in the treatment of
      depression.

PMID- 9580578
TI  - Lidocaine toxicity in primary afferent neurons from the rat.
AB  - Evidence from both clinical studies and animal models suggests that the local
      anesthetic, lidocaine, is neurotoxic. However, the mechanism of lidocaine-induced
      toxicity is unknown. To test the hypothesis that toxicity results from a direct
      action of lidocaine on sensory neurons we performed in vitro histological,
      electrophysiological and fluorometrical experiments on isolated dorsal root
      ganglion (DRG) neurons from the adult rat. We observed lidocaine-induced neuronal
      death after a 4-min exposure of DRG neurons to lidocaine concentrations as low as
      30 mM. Consistent with an excitotoxic mechanism of neurotoxicity, lidocaine
      depolarized DRG neurons at concentrations that induced cell death (EC50 = 14 mM).
      This depolarization occurred even though voltage-gated sodium currents and action
      potentials were blocked effectively at much lower concentrations. (EC50 values
      for lidocaine-induced block of tetrodotoxin-sensitive and -resistant voltage
      gated sodium currents were 41 and 101 microM, respectively.) At concentrations
      similar to those that induced neurotoxicity and depolarization, lidocaine also
      induced an increase in the concentration of intracellular Ca++ ions ([Ca++]i;
      EC50 = 21 mM) via Ca++ influx through the plasma membrane as well as release of
      Ca++ from intracellular stores. Finally, lidocaine-induced neurotoxicity was
      attenuated significantly when lidocaine was applied in the presence of nominally
      Ca(++)-free bath solution to DRG neurons preloaded with 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Our results indicate: 1)
      that lidocaine is neurotoxic to sensory neurons; 2) that toxicity results from a
      direct action on sensory neurons; and 3) that a lidocaine-induced increase in
      intracellular Ca++ is a mechanism of lidocaine-induced neuronal toxicity.

PMID- 9580579
TI  - Efflux of intracellular alpha-ketoglutarate via p-aminohippurate/dicarboxylate
      exchange in OK kidney epithelial cells.
AB  - The involvement of intracellular alpha-ketoglutarate (alpha-KG) in p
      aminohippurate (PAH) transport was investigated in OK kidney epithelial cells.
      Efflux of intracellular alpha-KG from the OK cells to the basolateral side was
      increased by applying PAH to the basolateral side of the cells. In contrast, the
      intracellular alpha-KG concentration was not influenced by the addition of PAH.
      The alpha-KG efflux across the basolateral membrane induced by PAH was higher
      than that across the apical membrane. Probenecid inhibited the PAH-dependent
      alpha-KG efflux. The alpha-KG efflux to the basolateral side was saturable with
      increasing concentration of PAH in the basolateral medium. Antimycin A, a
      metabolic inhibitor, inhibited [14C]PAH uptake across the basolateral membrane of
      OK cells in a dose-dependent manner. In addition, both the alpha-KG efflux
      induced by PAH and the intracellular alpha-KG concentration were decreased by
      antimycin A dose-dependently. These results directly show that alpha-KG generated
      by intracellular metabolism is effluxed via PAH/dicarboxylate exchange in the
      basolateral membrane of OK cells.

PMID- 9580580
TI  - Identification and characterization of human cytochrome P450 isoforms interacting
      with pimozide.
AB  - Using human liver microsomes (HLMs) and recombinant human cytochrome P450
      (CYP450) isoforms, we identified the major route of pimozide metabolism, the
      CYP450 isoforms involved, and documented the inhibitory effect of pimozide on
      CYP450 isoforms. Pimozide was predominantly N-dealkylated to 1,3-dihydro-1-(4
      piperidinyl)-2H-benzimidazol-2-one (DHPBI). The formation rate of DHPBI showed
      biphasic kinetics in HLMs, which suggests the participation of at least two
      activities. These were characterized as high-affinity (K(m1) and Vmax1) and low
      affinity (K(m2) and Vmax2) components. The ratio of Vmax1 (14 pmol/min/mg
      protein)/K(m1) (0.73 microM) was 5.2 times higher than the ratio of Vmax2 (244
      pmol/min/mg protein)/K(m2) (34 microM). K(m2) was 91 times higher than K(m1). The
      formation rate of DHPBI from 25 microM pimozide in nine human livers correlated
      significantly with the catalytic activity of CYP3A (Spearman r = 0.79, P = .028),
      but not with other isoforms. Potent inhibition of DHPBI formation from 10 microM
      pimozide was observed with ketoconazole (88%), troleandomycin (79%), furafylline
      (48%) and a combination of furafylline and ketoconazole (96%). Recombinant human
      CYP3A4 catalyzed DHPBI formation from 10 microM pimozide at the highest rate (V =
      2.2 +/- 0.89 pmol/min/pmol P450) followed by CYP1A2 (V = 0.23 +/- 0.08
      pmol/min/pmol P450), but other isoforms tested did not. The K(m) values derived
      with recombinant CYP3A4 and CYP1A2 were 5.7 microM and 36.1 microM, respectively.
      Pimozide itself was a potent inhibitor of CYP2D6 in HLMs when preincubated for 15
      min (Ki = 0.75 +/- 0.98 microM) and a moderate inhibitor of CYP3A (Ki = 76.7 +/-
      34.5 microM), with no significant effect on other isoforms tested. Our results
      suggest that pimozide metabolism is catalyzed mainly by CYP3A, but CYP1A2 also
      contributes. Pimozide metabolism is likely to be subject to interindividual
      variability in CYP3A and CYP1A2 expression and to drug interactions involving
      these isoforms. Pimozide itself may inhibit the metabolism of drugs that are
      substrates of CYP2D6.

PMID- 9580581
TI  - Effect of the Mdr1a P-glycoprotein gene disruption on the tissue distribution of
      SDZ PSC 833, a multidrug resistance-reversing agent, in mice.
AB  - The involvement of mdr1a P-glycoprotein (P-gP) on the tissue distribution of the
      multidrug resistance-reversing agent SDZ PSC 833 was assessed by use of mdr1a (-/
      ) mice. The mdr1a (-/-) and wild-type mdr1a (+/+) mice received a 4-h
      constantrate i.v. infusion (2 micrograms/min) of [14C]SDZ PSC 833. Mice were
      sacrificed at 0, 0.5, 1, 2 and 4 h during infusion and at 0.5, 1, 3, 8 and 24 h
      after stopping the infusion. Blood and tissues were analyzed on total (14C) and
      parental SDZ PSC 833 concentrations. Mdr1a (-/-) mice exhibited increased SDZ PSC
      833 accumulation in cerebrum, cerebellum and somewhat in testes and small
      intestine compared with the wild-type mice. The difference between mdr1a (-/-)
      and (+/+) brain (cerebrum and cerebellum) penetration depended on SDZ PSC 833
      blood concentrations, because this cyclosporin analog apparently governs its own
      brain penetration by inhibiting the P-glycoprotein pump in mdr1a (+/+) mice. Thus
      the mdr1a (-/-)/(+/+) ratio of brain concentrations tended to decrease and
      increase at high and low blood concentrations, respectively. These findings
      clearly demonstrate the interaction of SDZ PSC 833 with the P-glycoprotein
      present at the blood-brain barrier. The SDZ PSC 833 distribution in other mdr1a P
      glycoprotein-expressed tissues, as well as its metabolism and elimination, was
      not affected by the mdr1a gene disruption. This suggests that factors other than
      mdr1a P-gP are involved in the disposition of this multidrug resistance-reversing
      agent.

PMID- 9580582
TI  - The effects of buprenorphine on self-administration of cocaine and heroin
      "speedball" combinations and heroin alone by rhesus monkeys.
AB  - Concurrent abuse of cocaine and opioids is frequently observed clinically, and we
      have developed a model of "speedball" self-administration involving the
      simultaneous injection of cocaine and heroin combinations in rhesus monkeys
      (Mello et al. (1995) J Pharmacol Exp Ther 274:1325). In the present study, we
      evaluated the effects of buprenorphine (0.0075-0.75 mg/kg/day i.v.) and saline on
      speedball combinations of cocaine [0.001, 0.01 or 0.10 mg/kg/inj] and heroin
      [0.0001-0.032 mg/kg/inj]. We also examined the effects of buprenorphine (0.075
      and 0.237 mg/kg/day i.v.) on self-administration of heroin alone (0.0001-0.01
      mg/kg/inj). Drug and food (1-g banana pellets) self-administration were
      maintained on a second-order FR4 (VR16:S) schedule in four 1-hr sessions each
      day. Each buprenorphine or saline control treatment was evaluated for 10
      consecutive days, and monkeys returned to base-line performance between each
      treatment condition. Buprenorphine (0.075-0.75 mg/kg/day) selectively reduced
      self-administration of speedball combinations of low-dose cocaine (0.001
      mg/kg/inj) and heroin (0.001 or 0.0032 mg/kg/inj) (P < .05-.01), and
      buprenorphine (0.237 mg/kg/day) shifted dose-effect curves for speedball
      combinations of cocaine (0.001 mg/kg/inj) and heroin (0.0001-0.032 mg/kg/inj)
      downward (P < .05-.01) and approximately 1 log unit to the right. Buprenorphine
      treatment was less effective in decreasing responding maintained by speedball
      combinations of heroin and 0.01 and 0.10 mg/kg/inj cocaine. Buprenorphine
      treatment (0.075 and 0.237 mg/kg/day) also shifted the heroin dose-effect curve
      downward (P < .01-.001) and to the right. Both speedball and heroin self
      administration were associated with dose-dependent decreases in food-maintained
      responding during saline control treatment. However, food-maintained responding
      was often higher than control levels during buprenorphine treatment (P < .05
      .001), which suggests that buprenorphine antagonized the rate-decreasing effects
      of speedballs and of heroin. Buprenorphine's selective reduction of speedball and
      heroin self-administration is consistent with clinical treatment trials in opioid
      abusers and polydrug abusers. Thus, these primate models of speedball and heroin
      self-administration should be useful for preclinical evaluation of novel drug
      abuse treatment medications.

PMID- 9580583
TI  - Importance of chronopharmacokinetics in design and evaluation of transdermal drug
      delivery systems.
AB  - Circadian and meal effects on nicotine kinetics determine in part blood nicotine
      concentrations and in doing so may influence cigarette smoking behavior
      throughout the day. We have shown previously that nicotine clearance varies by
      approximately 17% (from peak to through) due to diurnal factors throughout the
      day and that meals increase nicotine clearance by about 42%. Until now
      pharmacokinetic analyses of nicotine absorption from patches have assumed a
      constant clearance of nicotine over 24 hr. Using 11 individual kinetic estimates
      from a previous study, we analyzed plasma nicotine concentrations vs. time data
      of two nicotine patch studies, and conducted a set of simulations to determine
      the extent to which time-varying kinetics would influence the design of
      transdermal drug delivery systems, intented to maintain a constant plasma
      nicotine concentration over 24 hr. Not incorporating time-varying kinetics leads
      to biased estimates of the delivery rate of the nicotine patches, and increases
      the variability in the delivery rates estimates. The hypothetical transdermal
      drug delivery systems designed assuming constant nicotine clearance results in a
      systematical underdosing during the first 12 hr after beginning therapy. The
      transdermal drug delivery systems obtained assuming the correct time-varying
      clearance shows three components: 1) an early high delivery rate, followed by 2)
      a rather constant, but slightly decreasing at night, release rate and 3)
      transient increases in delivery rate for 2 hr after each meal. The effect of
      circadian variations in clearance could be compensated for in patch design by
      decreasing the delivery rate during the night. Transient variations in clearance
      due to meals would require the corresponding use of rapid drug delivery dosage
      forms. The methods we devise to predict optimal dosing regimens in presence of
      chronopharmacokinetics might be useful for other medications in which blood
      levels need to be precisely controlled.

PMID- 9580584
TI  - Renal effects of glibenclamide: a micropuncture study.
AB  - The renal effects of glibenclamide were investigated using free flow
      micropuncture techniques in anesthetized Sprague-Dawley rats. Intravenous
      infusion of the drug (3 mg/hr) evoked a natriuresis and diuresis; potassium
      excretion remained unchanged. Fractional reabsorption in the proximal convoluted
      tubule in glibenclamide-infused rats did not differ significantly from that in
      control animals, although the late proximal tubular fluid to plasma concentration
      ratio for potassium was reduced. Fractional sodium delivery to the early distal
      tubule was elevated, while the fractional deliveries of water and potassium to
      this nephron site were unaffected. We conclude that glibenclamide impairs sodium
      reabsorption in one or more of the nephron segments that comprise the loop of
      Henle. These results are consistent with the hypothesis that the natriuresis
      resulting from glibenclamide administration is a consequence of blockade of
      potassium channels in the apical membrane of the thick ascending limb of Henle's
      loop. The data suggest that glibenclamide may additionally inhibit a small
      secretory potassium flux in the proximal tubule.

PMID- 9580585
TI  - Inhibitory effect of zinc protoporphyrin IX on lower esophageal sphincter smooth
      muscle relaxation by vasoactive intestinal polypeptide and other receptor
      agonists.
AB  - This study was performed in the opossum lower esophageal sphincter (LES) smooth
      muscle strips to determine the action of the heme oxygenase inhibitor zinc
      protoporphyrin IX (ZnPP IX) on the relaxant effect of vasoactive intestinal
      polypeptide and isoproterenol, which are known to stimulate adenylate cyclase
      (AC) via G protein coupling, and of the direct activator of AC catalytic subunit
      forskolin. To investigate the cGMP pathway, we examined the effect of atrial
      natriuretic factor known to activate the receptor linked to the particulate
      guanylate cyclase via G protein coupling and that of sodium nitroprusside [nitric
      oxide (NO) donor], authentic NO and carbon monoxide, which stimulate the
      intracellular soluble fraction of GC. The smooth muscle relaxation caused by
      nonadrenergic noncholinergic (NANC) nerve stimulation also was investigated. ZnPP
      IX caused concentration-dependent attenuation of the relaxant effect of
      vasoactive intestinal polypeptide, isoproterenol and atrial natriuretic factor
      without any effect on that of forskolin, sodium nitroprusside, NO and CO.
      Interestingly, ZnPP IX had no significant effect on the LES relaxation caused by
      NANC nerve stimulation and the smooth muscle contraction by bethanechol. From
      these results, we conclude that ZnPP IX attenuates the LES smooth muscle
      relaxation caused by the stimulation of G protein-coupled receptors to
      particulate AC and guanylate cyclase. The lack of effect of ZnPP IX on the NANC
      nerve-mediated LES relaxation suggests either lack of a role of heme oxygenase
      pathway in the response or an upregulation of NOS leading to normal LES
      relaxation.

PMID- 9580586
TI  - Mechanism of gallbladder relaxation in the cat: role of norepinephrine.
AB  - We investigated the mechanisms of neurally mediated relaxation of cat gallbladder
      muscle. Muscle strips from the gallbladder corpus placed in the muscle bath with
      oxygenated Krebs' solution developed spontaneous active tension. Tension was
      measured with isometric force transducers, and muscle relaxation was expressed as
      percent decrease of active basal tension. Electrical field stimulation (EFS)
      evoked a tetrodotoxin-sensitive and hexamethonium-insensitive frequency-dependent
      relaxation with a maximal relaxation at 20 Hz. Gallbladder muscle strips also
      relaxed in response to increasing concentrations of vasoactive intestinal peptide
      (VIP), isoproterenol and, after pretreatment with phentolamine, norepinephrine.
      Nitric oxide synthase inhibitors N omega-nitro-L-arginine and N omega-nitro-L
      arginine methyl ester at a concentration of 100 microM, which blocked EFS-induced
      relaxation in the lower esophageal sphincter, had no significant effect on EFS
      induced gallbladder muscle relaxation. The VIP antagonists VIP10-28 and [4Cl-D
      Phe6,Leu17]VIP at a concentration of 10 microM that blocked exogenous VIP-induced
      gallbladder relaxation also had no effect on the relaxation caused by EFS. In
      contrast, either propranolol or guanethidine at concentrations of > or = 1 microM
      significantly reduced EFS-evoked gallbladder relaxation (P < .01, analysis of
      variance). It is concluded that norepinephrine utilizing beta adrenergic
      receptors mediates EFS-stimulating postganglionic intramural neurons in the cat
      gallbladder.

PMID- 9580587
TI  - Characterization of endothelium-dependent relaxation independent of NO and
      prostaglandins in guinea pig coronary artery.
AB  - In the presence of N omega-nitro-L-arginine and indomethacin, acetylcholine (ACh)
      induced endothelium-dependent relaxation in guinea pig coronary artery
      preconstricted with 9,11-dideoxy-9 alpha, 11 alpha-epoxymethano prostaglandin F2
      alpha. Dexamethasone and arachidonyltrifluoromethyl ketone, inhibitors of
      phospholipase A2, and 17-octadecynoic acid, an inhibitor of cytochrome P450
      epoxygenase, had no effect on the response to ACh. Although proadifen, which is
      used widely as an inhibitor of cytochrome P450-dependent enzymes, suppressed the
      ACh-induced relaxation, the drug also inhibited the relaxation induced by
      cromakalim, a K+ channel opener. In isolated smooth muscle cells of guinea pig
      coronary artery, proadifen, but not 17-octadecynoic acid, almost abolished
      delayed rectifier K+ current. Epoxyeicosatrienoic acids failed to relax the
      artery. Apamin and iberiotoxin, inhibitors of small- and large-conductance Ca(++)
      activated K+ channels, respectively, did not affect the relaxation induced by
      ACh. A combination of charybdotoxin plus apamin, but not iberiotoxin plus apamin,
      abolished the response. However, the combination of charybdotoxin plus apamin had
      no effect on ACh-induced increase in intracellular free Ca++ concentration in
      endothelial cells. These results suggest that epoxyeicosatrienoic acids do not
      contribute to N omega-nitro-L-arginine/indomethacin-resistant relaxation induced
      by ACh in the guinea pig coronary artery. The present study also proposes that K+
      channels on vascular smooth muscle cells, which both charybdotoxin and apamin
      must affect for inhibition to occur, are the target for endothelium-derived
      hyperpolarizing factor.

PMID- 9580589
TI  - Signal transduction correlates of mu opioid agonist intrinsic efficacy: receptor
      stimulated [35S]GTP gamma S binding in mMOR-CHO cells and rat thalamus.
AB  - This study examined the signal transduction correlates of mu opioid agonist
      efficacy in two systems: mu receptor-transfected mMOR-CHO cell and rat thalamic
      membranes. The potency and maximal stimulation of [35S]GTP gamma S binding by
      various agonists was measured in the presence of excess GDP and compared with
      receptor binding affinity under identical assay conditions. Results showed that
      the relative maximal stimulation produced by these agonists was greater in mMOR
      CHO cell than in rat thalamic membranes; some drugs that were full agonists in
      mMOR-CHO cells were partial agonists in the thalamus, and some partial agonists
      in the transfected cells were full antagonists in the thalamus. Furthermore,
      there was receptor reserve for G-protein activation by some agonists in mMOR-CHO
      cell membranes, but no receptor reserve was detected in rat thalamic membranes.
      Saturation analysis of agonist-stimulated [35S]GTP gamma S binding revealed that
      full agonists produced both a higher Bmax and apparent affinity of [35S]GTP gamma
      S binding than partial agonists. Correlation of the Bmax and KD of agonist
      stimulated [35S]GTP gamma S binding with agonist intrinsic efficacy revealed only
      a moderate correlation with either parameter alone, but a highly significant
      correlation (r > 0.9) with a combination of the two parameters (Bmax/KD). These
      results suggest that the intrinsic efficacy of agonists at G-protein-coupled
      receptors is determined primarily by the ability of the agonist-occupied receptor
      to promote high-affinity GTP binding to the G-protein and to catalytically
      activate a maximal number G-proteins.

PMID- 9580588
TI  - Absorption and elimination of viper venom after antivenom administration.
AB  - The mechanisms by which antivenom neutralizes the venom are still poorly
      understood. In the present work, we studied the effects of antivenom, constituted
      with either F(ab')2 or Fab, on the processes of absorption and elimination of
      Vipera aspis venom in experimentally envenomed rabbits. We first concluded from
      this study that during the few hours after intramuscular injection, the venom
      rapidly disappeared from the site of injection but did not immediately reach the
      vascular system, suggesting that it is partly absorbed via the lymphatic
      circulation. Concerning the elimination process of the venom in the presence of
      antivenom, we observed that the elimination of F(ab')2/venom complexes is slower
      than that of free venom in the absence of antivenom but faster than that of free
      F(ab')2, suggesting that F(ab')2/venom complexes are eliminated by phagocytosis.
      The Fab/venom complexes, on the other hand, are eliminated more slowly than free
      Fab. These complexes are not eliminated through the renal route in agreement with
      their high molecular weight. In addition, we observed that the treatment of
      envenomed rabbits with antivenom made of Fab, but not F(ab')2, is responsible for
      an oliguria that could be responsible for clinical problems.

PMID- 9580590
TI  - Characterization of the uptake of rocuronium and digoxin in human hepatocytes:
      carrier specificity and comparison with in vivo data.
AB  - Mechanisms of drug transport in the liver have been investigated predominantly in
      rodents. Most of the in vitro drug research in the liver is performed in liver
      preparations of animals. The results of such experiments frequently are discussed
      in relation to anticipated metabolic profiles in man, but these extrapolations
      are often inappropriate because of large interspecies differences in drug
      metabolism. In the present study, the mechanisms and specificity of the uptake of
      the organic cation rocuronium and the cardiac glycoside digoxin were investigated
      in human hepatocytes and were compared with results obtained in rat hepatocytes.
      The extraction ratio for the intact liver was calculated from the measured uptake
      rates of the compounds in the human cells in vitro and compared with published in
      vivo data. The initial hepatic extraction ratio, calculated from the in vitro
      uptake data for digoxin and rocuronium, very well reflected the initial
      extraction ratio for distribution in the liver in vivo in man. Uptake of 100
      microM rocuronium was inhibited by 40 microM K-strophantoside (80% inhibition),
      and although not significantly, by 160 microM procainamide ethobromide, whereas
      no inhibitory effect was found in the presence of 160 microM taurocholic acid. In
      a previous study in rat hepatocytes, marked inhibition of digoxin uptake by
      quinine and only minimal inhibition by the diastereomer quinidine was
      demonstrated, showing clear stereoselectivity in transport inhibition.
      Unexpectedly, the uptake of digoxin in human hepatocytes was not inhibited
      significantly by quinidine or quinine, which indicates clear species differences.
      This is the first study to investigate the uptake mechanisms of organic cations
      and cardiac glycosides in human hepatocytes in some detail. The results show that
      uptake characteristics of drugs found in rats can not be extrapolated directly to
      humans.

PMID- 9580591
TI  - Gender differences in the expression of endothelin receptors in human saphenous
      veins in vitro.
AB  - The contractile response to endothelin-1 (ET-1) appears to be modulated by the
      relative density of ETA and ETB receptors. To determine the effects of gender on
      the distribution of ET receptors, we analyzed the endothelin receptor subtypes on
      membrane fractions prepared from saphenous vein samples obtained from patients of
      different genders undergoing coronary artery bypass graft surgery. The
      contractile response to ET-1 in the presence and absence of 1 microM of the ETA
      receptor antagonist BQ-123 was also investigated. Similar studies were repeated
      with endothelium-denuded samples to study the role of endothelium- and smooth
      muscle-derived ETB receptors. Competitive binding experiments were performed on
      membrane fractions using [125I]ET-1 and unlabeled ligands ET-1, ET-3, sarafatoxin
      6c and BQ-123. Analysis of the binding data with endothelium-intact samples
      yielded two classes of binding sites in both women and men. In women, the maximum
      binding capacities were 83 +/- 6 and 97 +/- 10 fmol/mg protein for ETA and ETB
      receptors, respectively; the corresponding values in men were 618 +/- 121 and 201
      +/- 10 fmol/mg protein. In addition, ET-1-induced contractions were 2-fold
      greater in men than in women at high ET-1 concentrations. Competitive binding
      studies with endothelium-denuded saphenous veins demonstrated the presence of
      only ETA receptors in both female and male tissue. These results indicate that
      the ratio and the density of ET receptors are different in men and women, which
      might be an important factor in the regulation of the contractile response.

PMID- 9580592
TI  - Differentiation of kappa opioid agonist-induced antinociception by naltrexone
      apparent pA2 analysis in rhesus monkeys.
AB  - Naltrexone (NTX) exhibited approximately 3-fold higher affinity for sites labeled
      by [3H]U69,593 (putative kappa 1-selective ligand) than [3H]bremazocine (non
      selective ligand) in the presence of mu and delta receptor blockade in monkey
      brain membranes. This led us to test an hypothesis that NTX could display in vivo
      antagonist selectivity for kappa 1-versus non-kappa 1-mediated effects. Six
      opioid agonists were characterized by NTX apparent pA2 analysis in a 50 degrees C
      water tail-withdrawal assay in rhesus monkeys. Constrained NTX pA2 values (95%
      confidence limits) were: alfentanil, 8.66 (8.47-8.85); ethylketocyclazocine, 7.97
      (7.93-8.01); U69,593, 7.64 (7.49-7.79); U50,488, 7.55 (7.42-7.67); bremazocine,
      6.92 (6.73-7.12); enadoline, 6.87 (6.69-7.05). Pretreatment with clocinnamox, an
      irreversible mu antagonist, confirmed that mu receptors were not involved in the
      antinociception produced by the kappa agonists, U69,593, U50,488, bremazocine and
      enadoline; however, both mu and kappa receptors mediated the antinociceptive
      effects of ethyl-ketocyclazocine. The apparent NTX pA2 profile of opioid agonists
      correlated highly with the radioligand binding studies, which indicates that
      U69,593 and U50,488 produced antinociception by acting on kappa-1 receptors,
      whereas bremazocine and enadoline probably acted via non-kappa-1 receptors. This
      study provides further functional evidence of kappa opioid receptor multiplicity
      in primates and suggests that NTX may be a useful tool to study this phenomenon
      in vivo.

PMID- 9580593
TI  - Glycine site antagonists and partial agonists inhibit N-methyl-D-aspartate
      receptor-mediated [3H]arachidonic acid release in cerebellar granule cells.
AB  - Activation of N-methyl-D-aspartate (NMDA) receptors is known to produce
      arachidonic acid release, which has been implicated in excitotoxicity.
      Antagonists and partial agonists at the glycine site of the NMDA receptor,
      despite exhibiting functional differences in electrophysiological studies,
      inhibit glutamate-induced neurotoxicity and ischemia-induced neurodegeneration.
      The objective of this study was to investigate the effects of both glycine site
      antagonists and partial agonists on NMDA receptor-mediated [3H]arachidonic acid
      (AA) release evoked by glutamate, NMDA or a competitive inhibitor of the
      glutamate/aspartate uptake carrier. The [3H]AA release evoked by a maximally
      effective concentration of glutamate (100 microM) was blocked by the glycine site
      antagonists 7-chlorokynurenic acid (7-CKYN) and 5,7-dichlorokynurenic acid (5,7
      DCKYN) and by a low intrinsic efficacy glycine partial agonist (+)-1-hydroxy-3
      aminopyrrolid-2-one [(+)-HA-966]. 1-Aminocyclopropanecarboxylic acid (ACPC), a
      high intrinsic efficacy glycine partial agonist, did not modify [3H]AA release
      evoked by 100 microM glutamate. However, ACPC blocked (in a glycine reversible
      manner) the [3H]AA release induced by NMDA (100 microM) with an IC50 of 131 +/- 2
      microM. Furthermore, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a competitive
      inhibitor of the glutamate transporter, also released [3H]AA (Emax and EC50 of
      127 +/- 4% and 30 +/- 1 microM, respectively). ACPC, 7-CKYN and (+/-)-2-amino-7
      phosphonoheptanoic acid (AP-7), a competitive NMDA receptor antagonist, inhibited
      [3H]AA release evoked by PDC. These results demonstrate that both glycine site
      antagonists and partial agonists can inhibit NMDA receptor-mediated [3H]AA
      release in cerebellar granule cells, an action consistent with the
      neuroprotective effects of these compounds.

PMID- 9580594
TI  - S-(+)-3-isobutylgaba and its stereoisomer reduces the amount of inflammation and
      hyperalgesia in an acute arthritis model in the rat.
AB  - The present study investigated whether spinal administration of S-(+)-3
      isobutylgaba (S-(+)-3-IBG) or its stereoisomer, R-(-)-3-isobutylgaba (R-(-)-3
      IBG), are effective in reducing the hyperalgesia and swelling observed after
      injection of kaolin and carrageenan into the knee joint of the rat. The effects
      of pretreatment and post-treatment of S-(+)-3-IBG, R-(-)-3-IBG and artificial
      cerebrospinal fluid (aCSF) on the swelling, pain-related behavior scores and the
      heat hyperalgesia induced by knee joint inflammation were compared. Infusion of
      either S-(+)-3-IBG or R-(-)-3-IBG through a microdialysis fiber, implanted in the
      dorsal horn of the spinal cord, for 1.5 h before injection of kaolin and
      carrageenan resulted in a 20 to 30% reduction in joint swelling compared with
      aCSF-treated controls, and prevented the development of heat hyperalgesia and
      spontaneous pain. In contrast, infusion of either stereoisomer after the
      development of inflammation reduced the hyperalgesia but did not reduce the
      amount of joint swelling compared with aCSF-treated animals. In summary, S-(+)-3
      IBG and R-(-)-3-IBG are effective antihyperalgesic agents when administered both
      before and after joint inflammation. In addition, if administered before
      injection of kaolin and carrageenan into the knee joint this drug can attenuate
      joint inflammation. Both the antihyperalgesic and anti-inflammatory properties of
      this drug probably are mediated through a central neurogenic mechanism.

PMID- 9580595
TI  - The methylglutamate, SYM 2081, is a potent and highly selective agonist at
      kainate receptors.
AB  - The methylglutamate analog (2S,4R)-4-methylglutamate (SYM 2081) has been shown to
      potently displace high affinity [3H]kainate binding to cortical tissue and to
      recombinant kainate receptors, and to evoke rapidly desensitizing responses in
      electrophysiological recordings. We have used two electrode voltage clamp
      recordings to compare the potency and efficacy of SYM 2081 with other alpha-amino
      3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)/kainate receptor agonists at
      homomeric kainate and AMPA receptors expressed in Xenopus oocytes. In the
      presence of concanavalin A to reduce agonist induced desensitization at kainate
      receptors, SYM 2081 was a potent agonist at homomeric kainate receptors composed
      of the GluR5 and GluR6 subunit, with an EC50 of 0.12 +/- 0.02 and 0.23 +/- 0.01
      microM, respectively. SYM 2081 was highly selective for kainate receptors, the
      EC50 for activation of AMPA receptors composed of the GluR1 and GluR3 subunits
      was 132 +/- 44 and 453 +/- 57 microM, respectively. Other methylglutamate analogs
      were tested for kainate receptor agonist activity. Methylglutamate compounds with
      the methyl group at the 2 or 3 position of glutamate were inactive indicating
      that positioning of the methyl group at the 4 position was essential for agonist
      activity. Of the four stereoisomers of 4-methylglutamate, SYM 2081 (2S,4R) was
      the most potent agonist. The (2R,4R) isomer was estimated to be 20-fold and the
      (2S,4S)-isomer approximately 1000-fold less potent than SYM 2081. These results
      indicate that SYM 2081 is a potent and selective agonist at kainate receptors,
      and thus will be a useful ligand for evaluating the role of kainate receptors in
      central nervous system function and disease.

PMID- 9580596
TI  - Open state block by fendiline of L-type Ca++ channels in ventricular myocytes
      from rat heart.
AB  - The effects of fendiline on L-type Ca++ currents [ICa(L)] were investigated in
      rat ventricular cardiomyocytes using the patch-clamp technique both in the whole
      cell disrupted-patch and in the cell-attached configuration. For comparison, the
      effects of verapamil were also investigated. Both compounds depressed the
      magnitude of whole cell ICa(L), verapamil being about 15 times more potent than
      fendiline. Verapamil did not change the time course of the current, whereas
      fendiline accelerated its decay when either Ca++ or Ba++ ions were used as charge
      carriers. In the presence of the Ca++ agonist BayK8644 (10 microM), the potency
      ratio of fendiline/verapamil was inverted. BayK8644 (10 microM) also reversed the
      potency ratio of verapamil/fendiline in smooth muscle, with respect to changes in
      tension induced by K+ (48 mM). In single channel recordings at 0.1 Hz, in the
      presence of BayK8644 (1 microM) and using Ba++ ions as the charge carrier,
      fendiline (1 microM) reduced mean open time by 34% and channel availability by
      8%; the ensemble average current of Ca++ channels was reduced by 43%. In the same
      experimental conditions, verapamil (1 microM) was ineffective. These results can
      be explained by the assumption that fendiline blocks Ca++ channels preferentially
      in the open state, in contrast to verapamil which blocks preferentially
      inactivated Ca++ channels.

PMID- 9580597
TI  - Evaluation of cannabinoid receptor agonists and antagonists using the guanosine
      5'-O-(3-[35S]thio)-triphosphate binding assay in rat cerebellar membranes.
AB  - Cannabinoid receptors are members of the superfamily of G protein-coupled
      receptors. Their activation has previously been shown to stimulate guanosine 5'-O
      (3-[35S]thio)-triphosphate ([35S]GTP gamma S) binding in a range of brain regions
      using both membrane preparations and autoradiography. This study evaluates the
      activities of structurally diverse cannabinoid receptor ligands in the GTP gamma
      S binding assay, comparing the relationship between receptor binding and
      activation and also examining efficacy differences between compounds. Using rat
      cerebellar membrane preparations, the effects of GDP concentration on GTP gamma S
      binding and the activities of a range of cannabinoid receptor ligands, including
      the CB1 selective antagonist SR141716A, were investigated. GDP concentration was
      found to have differing effects on cannabinoid-stimulated [35S]GTP gamma S
      binding depending on the nature of the agonist used. The stimulation produced by
      high efficacy compounds, such as CP 55,940 and WIN 55212-2, was increased by
      raising the GDP concentration, but that of a low efficacy agonist, (-)-delta
      tetrahydrocannabinol, was decreased. Of the cannabinoid compounds tested, a wide
      range of potencies (EC50) and levels of maximal stimulation (Emax) were observed.
      These ranged from CP 55,244 (Emax of 165, 148-183%, and an EC50 of 0.47, 0.22
      0.96, nM) through (-)-delta-tetrahydrocannabinol, cannabinol and anandamide,
      which produced no concentration-dependent stimulation of [35S]GTP gamma S binding
      under the same conditions. SR141716A competitively antagonized all the agonists
      against which it was tested, providing equilibrium dissociation constants (Kd
      values) in the sub-nanomolar range (0.06-0.40 nM), implicating a CB1 receptor
      mediated response. These results provide a more detailed characterization of the
      cannabinoid-stimulated [35S]GTP gamma S binding assay than has previously been
      reported.

PMID- 9580598
TI  - Levels of endogenous adenosine in rat striatum. I. Regulation by ionotropic
      glutamate receptors, nitric oxide and free radicals.
AB  - Glutamate release after ischemia, hypoxia and seizure activity plays an important
      role in stimulating adenosine production and release. We characterized the
      ionotropic glutamate receptor subtype that regulates adenosine levels in vivo and
      investigated the role of nitric oxide and free radicals in mediating N-methyl-D
      aspartate (NMDA)-induced increases in adenosine levels. Rats received unilateral
      intrastriatal injections and were sacrificed 15 min postinjection by high-energy
      focused microwave irradiation (10 kW, 1.25 s). Adenosine levels were measured by
      high-performance liquid chromatography in ipsilateral and contralateral striata.
      NMDA and kainic acid dose-dependently increased levels of adenosine whereas (+/-)
      alpha-amino-3-hydroxy-5-methyl-4-isoxazol proprionic acid had no effect. The NMDA
      and kainic acid-induced increases were blocked by dizocilpine, and the kainic
      acid response was decreased by 6-cyano-7-nitroquinoxaline-2,3-dione. The effects
      of NMDA and kainic acid on levels of adenosine were not additive. Intrastriatal L
      arginine decreased, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine
      methyl ester, increased basal adenosine levels. Coadministration of NMDA with L
      arginine or NG-nitro-L-arginine methyl ester did not significantly affect NMDA
      induced increases in levels of adenosine. N-Tert-butyl-phenylnitrone, a free
      radical scavenger, reversed L-arginine-induced decreases and NMDA-induced
      increases in levels of adenosine. Together, these results indicate that NMDA-type
      ionotropic receptors play an important role in regulating in vivo levels of
      adenosine in rat striatum and that free radicals, but not nitric oxide,
      apparently are involved in NMDA-induced increases in levels of adenosine.
      Conversely, nitric oxide, but not free radicals, apparently exert tonic control
      over basal levels of endogenous adenosine.

PMID- 9580599
TI  - Levels of endogenous adenosine in rat striatum. II. Regulation of basal and N
      methyl-D-aspartate-induced levels by inhibitors of adenosine transport and
      metabolism.
AB  - Selective inhibitors of adenosine production, degradation and transport were used
      to potentiate in vivo levels of adenosine and to determine the source of both
      basal and N-methyl-D-aspartate (NMDA)-induced increases in levels of endogenous
      adenosine in vivo. Male Sprague-Dawley rats receiving unilateral intrastriatal
      injections of pharmacological agents were sacrificed 15 min postinjection by high
      energy focused microwave irradiation (10 kW, 1.25 s). Ipsilateral and
      contralateral striata were dissected, and adenosine levels were measured by high
      performance liquid chromatography. Inhibition of 5'-nucleotidase by alpha, beta
      methylene ADP dose-dependently decreased adenosine levels under basal as well as
      NMDA-stimulated conditions. Inhibition of nucleoside transport by dilazep and
      adenosine deaminase by 2'-deoxycoformycin each dose-dependently increased basal
      adenosine levels. 2'-Deoxycoformycin potentiated NMDA-induced increases in
      adenosine levels. Inhibition of adenosine kinase by 5'-amino-5'-deoxyadenosine
      increased basal levels of adenosine, but did not significantly affect NMDA
      induced increases in adenosine. 2'-Deoxycoformycin combined with 5'-amino-5'
      deoxyadenosine produced a greater enhancement of NMDA-induced increases in levels
      of adenosine than when either drug was administered separately. Endogenous
      adenosine in vivo apparently originates from release of adenosine as well as from
      release and extracellular breakdown of a nucleotide under both basal and NMDA
      stimulated conditions. Furthermore, inhibitors of adenosine kinase and adenosine
      deaminase work best to increase levels of endogenous adenosine under basal and
      NMDA-stimulated conditions, respectively.

PMID- 9580600
TI  - Characterization of the histamine H2 receptor structural components involved in
      dual signaling.
AB  - We previously demonstrated that the histamine H2 receptor can activate both
      adenylate cyclase (AC) and phospholipase C (PLC) signaling pathways via separate
      GTP-dependent mechanisms. We examined whether H2 receptor-specific peptides
      corresponding to the amino (N) or carboxyl terminus (C) of the second (2i) or
      third (3i) intracytoplasmic loops or the carboxyl terminal tail (P4iN) could
      effect histamine- stimulated AC and PLC activity in cell membranes prepared from
      HEPA cells stably transfected to express the canine H2 histamine receptor cDNA.
      Tiotidine binding and basal signaling were not altered by the synthetic peptides.
      H2P2iN, H2P2iC, H2P3iN and H2P4iN did not effect histamine stimulated AC activity
      although H2P3iC (10(-4) M) significantly inhibited this parameter (65.6 +/- 7.2%
      of maximal stimulation) (n = 6). Combination of the five peptides (H2P2iN,
      H2P2iC, H2P3iN, H2P3iC and H2P4iN) abolished histamine stimulated AC activity.
      Although all of the peptides inhibited histamine-stimulated PLC activity to a
      moderate degree individually, H2P3iC (10(-4) M) had the greatest effect,
      decreasing PLC activation to 20.8 +/- 6.3% of maximal stimulation (IC50 = 7.5 X
      10(-7) M) (n = 6). H2P3iC and the peptide combination did not alter, forskolin,
      GTP gamma s or epinephrine-stimulated AC activity nor GTP gamma s and vasopressin
      stimulated PLC. These studies demonstrate that both the second and third
      intracytoplasmic loops of the histamine H2 receptor are linked to separate
      signaling pathways in a differential manner.

PMID- 9580602
TI  - Effects of 8-bromo-cyclic GMP on membrane potential of single swine tracheal
      smooth muscle cells.
AB  - Cyclic GMP relaxes swine tracheal smooth muscle. Relaxation occurs because of
      decreases in intracellular calcium concentration ([Ca++]i) that are thought to
      occur through hyperpolarization which inhibits calcium influx. Activation of K+
      channels has been suggested as the underlying mechanism for the
      hyperpolarization. In the present study, the effects of 8-bromoguanosine 3',5'
      cyclic monophosphate (8-Br-cGMP, a membrane-permeable analog of cyclic GMP) on
      acetylcholine (ACh)-induced increases in [Ca++]i were examined by laser scanning
      confocal microscopy in fluo 3-loaded single cells. Membrane potential and
      currents were measured by the perforated-configuration of patch-clamp method, 8
      Bromo-cGMP (1 microM-0.1 mM) inhibited 0.1 microM ACh-induced oscillations in
      [Ca++]i in a concentration-dependent manner. Spontaneous changes in membrane
      potential were observed by the patch-clamp method. Acetylcholine (0.03 microM)
      did not affect the time-averaged mean potential. The spontaneous changes in
      membrane potential were reduced and the cells were depolarized by 0.1 microM ACh
      and to a greater degree by 1 microM ACh. This result is consistent with previous
      observations of ACh-induced depolarization in intact tissue. The application of
      0.1 mM 8-Br-cGMP had no significant effects on spontaneous changes in membrane
      potential and did not induce changes in membrane potential in cells treated with
      0.1 microM ACh. In voltage-clamped cells, ACh (0.1 microM) induced oscillations
      in calcium-activated K+ currents. 8-Bromo-cGMP (0.1 mM) inhibited these ACh
      induced oscillations in currents, but had no significant effects on spontaneous
      changes in membrane current in unstimulated cells. These data indicate that 8-Br
      cGMP inhibits ACh-induced increases in [Ca++]i by mechanisms other than
      regulation of membrane potential.

PMID- 9580603
TI  - kappa-Opioid receptor binding populations in rhesus monkey brain: relationship to
      an assay of thermal antinociception.
AB  - The binding characteristics of the kappa opioid ligands [3H]U69,593 and
      [3H]bremazocine, the mu opioid ligand [3H][D-ala2,N-Me-Phe4,glycol5]enkephalin
      and the delta opioid ligand [3H]p-Cl-[D-pen2,5]enkephalin were studied in rhesus
      monkey brain membranes in saturation binding experiments and were followed by
      competition binding experiments with a variety of peptidic and nonpeptidic opioid
      ligands. The [3H]U69,593 sites appeared to be a subset of kappa opioid receptors
      (kappa-1 receptors: Kd, 1.2 nM; Bmax, 66 fmol/mg). [3H]Bremazocine (in the
      presence of mu and delta receptor-masking agents), bound to a larger population
      of kappa receptors (kappa-all: Kd, 0.39 nM; Bmax, 227 fmol/mg), which presumably
      included the aforementioned kappa-1 sites. Competition binding experiments
      revealed that the presently defined kappa-1 sites were similar to previously
      reported sites in other mammalian species, particularly in terms of the higher
      kappa-1 selectivity observed with arylacetamide (e.g., U50,488) vs. benzomorphan
      kappa agonists (e.g., ethylketocyclazocine). The kappa-selective antagonist
      norbinaltorphimine (nor-BNI) displayed a very small (2.3-fold) selectivity for
      kappa-1 vs. kappa-all sites. This led to the prediction that in rhesus monkeys (n
      = 3), systemically administered nor-BNI (10 mg/kg s.c.) should have a very
      moderate degree of antagonist selectivity for the antinociceptive effects of a
      putative kappa-1-agonist, the arylacetamide U50,488 (0.1-3.2 mg/kg s.c.), vs.
      those of the benzomorphan kappa agonist ethylketocyclazocine (0.01-056 mg/kg
      s.c.). This prediction was confirmed in vivo because nor-BNI (10 mg/kg) caused a
      robust and long lasting (up to 21 days) antagonism of the antinociceptive effects
      of U50,488 and a small but significant antagonism of ethylketocyclazocine. The
      arylacetamide congener Cl-977 (enadoline), which displayed an 11-fold kappa-1 vs.
      kappa-all binding selectivity, was not sensitive to nor-BNI pretreatment. This
      indicates that the kappa subtype-binding profile of an agonist is not necessarily
      predictive of its sensitivity to nor-BNI in vivo. Overall, the present results
      suggest that at least two functional kappa receptor populations may be present in
      rhesus monkey brain.

PMID- 9580601
TI  - Differential effects of chronic antidepressant treatment on swim stress- and
      fluoxetine-induced secretion of corticosterone and progesterone.
AB  - Hypersecretion of cortisol occurs in numerous patients with major depression and
      normalizes with clinical recovery during the course of chronic antidepressant
      treatment. These clinical data suggest that investigation of the effects of
      antidepressant treatments on the regulation of the brain-pituitary-adrenal axis
      may assist in elucidating the therapeutic basis of antidepressant actions. In the
      present investigation, both swim stress and acute fluoxetine challenge increased
      release of corticosterone and progesterone to reflect an activation of the brain
      pituitary-adrenal axis. The effects of chronic antidepressant treatment (21 days)
      on corticosterone and progesterone secretion induced by these challenges were
      investigated. Chronic fluoxetine treatment (5 mg/kg/day) completely blocked the
      increased secretion of corticosterone and progesterone in response to the acute
      fluoxetine challenge. Chronic treatment with desipramine, imipramine or
      amytriptyline (15 mg/kg/day) also markedly attenuated fluoxetine-induced
      corticosterone and progesterone secretion. However, chronic treatment with the
      monoamine oxidase inhibitors, phenelzine (5 mg/kg) and tranylcypromine (5 mg/kg),
      did not affect this hormonal response to acute fluoxetine challenge. Plasma
      levels of fluoxetine after acute challenge were not significantly different for
      the various chronic antidepressant treatment conditions from the chronic saline
      controls; therefore, an increase in the metabolism of fluoxetine can not explain
      the antagonism of the fluoxetine-induced hormonal response after chronic
      antidepressant treatment. In contrast to the effects of selected antidepressants
      on acute fluoxetine-induced steroid release, chronic treatment with imipramine
      (20 mg/kg/day), fluoxetine (5 mg/kg/day) or phenelzine (5 mg/kg) did not
      significantly alter this swim stress-induced corticosterone or progesterone
      secretion. Because chronic fluoxetine and tricyclic antidepressant drugs blocked
      the acute action of fluoxetine to increase adrenal cortical secretion, but did
      not alter swim stress-induced secretion of these steroids, we propose that
      distinct neurochemical mechanisms control fluoxetine and swim stress-induced
      steroid release. We speculate that the substantial adaptive response to those
      chronic antidepressant treatments, which minimize the effect of acute fluoxetine
      challenge to increase in corticosterone and progesterone secretion, may be
      relevant to the therapeutic actions of these drugs.

PMID- 9580604
TI  - Inhibition of 5-lipoxygenase diminishes neurally evoked tachykinergic contraction
      of guinea pig isolated airway.
AB  - The role of endogenous 5-lipoxygenase products in modulating tachykinergic
      neurotransmission in guinea pig isolated trachea was investigated. Tachykinin
      containing afferent nerve fibers were stimulated with either electrical field
      stimulation or antidromic stimulation of the right vagus nerve. This resulted in
      contractions of the isolated caudal trachea and bronchus that could be blocked
      with either tetrodotoxin or a combination of neurokinin-1 and neurokinin-2
      receptor antagonists. The 5-lipoxygenase inhibitor ZD 2138 (1 microM)
      significantly inhibited these neurally mediated tachykinergic contractions, by
      approximately 50%, yet had no effect on the contractions evoked by stimulating
      tachykinergic fibers in an action potential-independent fashion with capsaicin or
      by exogenously applied neurokinin A. The effect of ZD 2138 on action potential
      driven tachykinergic contractions was mimicked by pobilukast, pranlukast,
      montelukast and zafirlukast, four structurally unrelated antagonists of the
      cysteinyl leukotriene 1 receptor subtype. Pobilukast had no effect on the
      tachykinergic contraction in tissues pretreated with ZD 2138. Likewise, ZD 2138
      had no effect on the tachykinergic contractions in tissues pretreated with
      pobilukast. Intracellular electrophysiological recording of the membrane
      properties of jugular ganglion neurons, the source of tachykinins in the guinea
      pig trachea/bronchus, demonstrated that leukotriene D4 caused a membrane
      depolarization of vagal afferent C-fiber neurons and an increase in input
      impedance, both of which were abolished by zafirlukast. Taken together, these
      data indicate that in the resting guinea pig isolated trachea/bronchus,
      endogenous 5-lipoxygenase activity leads to the production of cysteinyl
      leukotrienes that amplify action potential-dependent release of tachykinins from
      airway afferent nerve fibers.

PMID- 9580605
TI  - Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2
      oxoglutarate carriers.
AB  - The role of organic anion transporters in the mitochondrial uptake of glutathione
      (GSH) was investigated by assessing competition with substrates or inhibition
      with inhibitors of specific carriers and modulation of mitochondrial energetics.
      Potential artifacts in the transport methodology, including contamination of
      matrix space with extramitochondrial fluid, changes in matrix volume during
      incubations, efflux of transported GSH during sample processing, induction of the
      membrane permeability transition, contamination of the mitochondrial preparation
      with plasma membranes and GSH degradation, were corrected or eliminated.
      Substrates (i.e., malate, succinate) and an inhibitor (i.e., butylmalonate) of
      the dicarboxylate carrier, an inhibitor (i.e., phenylsuccinate) of the 2
      oxoglutarate carrier, and glutamate produced significant inhibition of GSH uptake
      whereas substrates and inhibitors of the mono- and tricarboxylate carriers were
      generally without effect. Phosphoenolpyruvate, which is a substrate for the
      tricarboxylate carrier, inhibited GSH uptake, but this was due to induction of
      the membrane permeability transition and not to competition for uptake. Although
      glutamate inhibited GSH uptake, the converse did not occur. GSH uptake was pH
      independent and aspartate had no effect, which suggest that the glutamate and
      glutamate-aspartate carriers are not involved in GSH uptake but that the glutamyl
      residue of GSH may be important in its transport. GSH uptake was dependent on
      phosphate and ATP generation. Hence, we conclude that both the dicarboxylate and
      2-oxoglutarate carriers of the inner membrane can catalyze uptake of GSH into the
      matrix. The function of an additional, novel transporter cannot be excluded at
      present. This is the first study to define the function of mitochondrial anion
      carriers in GSH transport.

PMID- 9580606
TI  - Activity-dependent neurotrophic factor: structure-activity relationships of
      femtomolar-acting peptides.
AB  - Activity-dependent neurotrophic factor (ADNF) is a glia-derived protein that is
      neuroprotective at femtomolar concentrations. A 14-amino acid peptide of ADNF
      (ADNF-14) has been reported that protects cultured neurons from multiple
      neurotoxins. Structure-activity relationships of peptides related to ADNF-14 now
      have been determined. A 9-amino acid core peptide (ADNF-9) has been identified
      that has greater potency and a broader effective concentration range (10(-16) to
      10(-13) M) than ADNF or ADNF-14 in preventing cell death associated with
      tetrodotoxin treatment of cerebral cortical cultures. Deletions or conservative
      amino acid substitutions to ADNF-9 resulted in reduced potency, narrower
      effective concentration range and/or decreased efficacy. Removal of the N
      terminal serine or the COOH-terminal isoleucine-proline-alanine from ADNF-9
      produced a significant reduction in survival-promoting activity. Comparative
      studies of ADNF-9 action in mixed (glia plus neurons) vs. glia-depleted neuronal
      cultures indicated that ADNF-9 can act directly on neurons, although the potency
      of the peptide was 10,000-fold greater in mixed cultures. Kinetic studies showed
      that exposure to ADNF-9 for only 2 hr was sufficient to produce a 4-day
      protection against the cell-killing action of tetrodotoxin. Treatment with
      bafilomycin A1 (an inhibitor of receptor-mediated endocytosis) for 2 hr prevented
      the ADNF- and ADNF-9-mediated neuroprotection. ADNF-9, like ADNF-14, was
      neuroprotective against N-methyl-D-aspartate and the beta-amyloid peptide (amino
      acids 25-35), and had a much broader range of effective concentrations than ADNF
      14. These studies identify ADNF-9 as an attractive lead compound for the
      development of therapeutic agents against neurodegenerative diseases.

PMID- 9580607
TI  - Actions of A-131701, a novel, selective antagonist for alpha-1A compared with
      alpha-1B adrenoceptors on intraurethral and blood pressure responses in conscious
      dogs and a pharmacodynamic assessment of in vivo prostatic selectivity.
AB  - A-131701 (3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b, hexahydro-[1H]
      benz[e]isoindol-2-yl)ethyl]pyrido [3',4': 4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)
      dione) is a novel compound previously shown to be selective for alpha-1a sites
      compared with alpha-1b adrenoceptors in radioligand binding studies and isolated
      tissue bioassays and to block canine urethral pressure (IUP) responses to
      exogenous alpha-1 adrenergic agonists to a greater extent than blood pressure
      responses. In conscious dogs in which IUP and mean arterial blood pressure (MABP)
      responses were measured periodically up to 24 hr, A-131701 blocked phenylephrine
      (PHE)-induced increases in IUP to a greater extent than MABP responses, and the
      blockade of the IUP effects of PHE was significantly different from control for
      up to 12 hr after doses greater than 0.3 mg/kg p.o., whereas blood pressure
      effects were of a lesser extent and duration. In addition to the weak antagonism
      of PHE-induced blood pressure responses, A-131701 also exhibited minimal effects
      on basal blood pressure in the dog, unlike terazosin, doxazosin or tamsulosin.
      Pharmacokinetic analysis of plasma samples from dogs indicated that A-131701 had
      a half-life of 0.4 to 0.8 hr and a bioavailability of 30 to 50% in dogs. Somewhat
      longer half-lives were observed in rat and monkey, with bioavailability values in
      the 25 to 30% range. Evidence of nonlinearity of pharmacokinetics was obtained in
      dogs and monkeys. Pharmacodynamic analysis revealed differences between A-131701
      and nonselective alpha-1 adrenoceptor antagonists in selectivity for prostatic
      versus vascular alpha-1 adrenoceptors based on either extent or duration of
      blockade, which were either similar to or superior to compounds such as
      tamsulosin or REC 15/2739. These data demonstrate that A-131701 selectively
      blocks canine prostatic alpha-1 adrenoceptors for prolonged periods compared with
      MABP responses in vivo. Therefore, A-131701 should have clinical utility in the
      pharmacotherapy of benign prostatic hyperplasia.

PMID- 9580608
TI  - 5-Hydroxytryptamine2 receptors modulate auditory filtering in the rat.
AB  - Sensory processing deficits are a hallmark of schizophrenia and can be
      demonstrated by recording auditory evoked potentials (AEPs) elicited in response
      to closely paired click stimuli. In nonschizophrenic humans, as well as in rats,
      the amplitude of the response to the second click is reduced (filtered) compared
      with the first. In contrast, schizophrenics, or rats treated with amphetamine,
      generate AEPs that have smaller amplitudes and show little or no reduction in the
      response to the second click. We sought to evaluate the role of 5
      hydroxytryptamine2 5-HT2 receptors in auditory filtering. Male Sprague-Dawley
      rats were implanted with a skull screw electrode to permit chronic recording of
      AEPs from a point approximating human vertex. During subsequent recording
      sessions, pairs of clicks (a conditioning click followed by a test click) were
      presented 500 msec apart. Parameters of N40, a dominant midlatency component of
      the AEP, were examined to evaluate the effects of a 5-HT2 receptor agonist, (+/-)
      2,5-dimethoxy-4-iodoamphetamine (DOI), and a 5-HT2 receptor antagonist,
      ketanserin. Systemic administration of ketanserin reduced sensory filtering in a
      dose-dependent manner. Conversely, DOI significantly improved filtering. In
      addition, DOI dose-dependently antagonized the disruption of filtering induced by
      administration of amphetamine (1.83 mg/kg i.p.). Taken together, these results
      indicate an important role for 5-HT2 receptors in the modulation of auditory
      filtering.

PMID- 9580609
TI  - Mutation of a highly conserved aspartate residue in the second transmembrane
      domain of the cannabinoid receptors, CB1 and CB2, disrupts G-protein coupling.
AB  - The cannabinoid receptors, CB1 and CB2, are members of the G-protein coupled
      receptor family and share many of this family's structural features. A highly
      conserved aspartic acid residue in the second transmembrane domain of G-protein
      coupled receptors has been shown for many of these receptors to be functionally
      important for agonist binding and/or G-protein coupling. To determine whether
      this residue is involved in cannabinoid receptor function, we used site-directed
      mutagenesis of receptor cDNA followed by expression of the mutant receptor in HEK
      293 cells. Aspartate 163 (in CB1) and aspartate 80 (in CB2) were substituted with
      either asparagine or glutamate. Stably transfected cell lines were tested for
      radioligand binding and inhibition of cAMP accumulation. Binding of the
      cannabinoid receptor agonist [3H]CP-55,940 was not affected by either mutation in
      either the CB1 or CB2 receptor, nor were the affinities of anandamide or (-)
      delta 9-tetrahydrocannabinol. Binding of the CB1-selective receptor antagonist
      SR141716A also was unaltered. However, the affinity of WIN 55,212-2 was
      attenuated significantly in the CB1, but not the CB2, mutant receptors. Studies
      examining inhibition of cAMP accumulation showed reduced effects of cannabinoid
      agonists in the mutated receptors. Our data suggest that this aspartate residue
      is not generally important for ligand recognition in the cannabinoid receptors;
      however, it is required for communication with G proteins and signal
      transduction.

PMID- 9580610
TI  - NO-independent vasodilation to acetylcholine in the rat isolated kidney utilizes
      a charybdotoxin-sensitive, intermediate-conductance Ca(++)-activated K+ channel.
AB  - The role of K+ channels in the nitric oxide-independent renal vasodilator effect
      of acetylcholine (Ach) was examined to address the hypothesis that the mechanism
      underlying this response was different from that of bradykinin, because an
      earlier study indicated the possibility of different mediators. We used the rat
      isolated, perfused kidney that was constricted with phenylephrine and treated
      with nitroarginine and indomethacin to inhibit nitric oxide synthase and
      cyclooxygenase, respectively. The nonspecific K+ channel inhibitors, procaine and
      tetraethylammonium (TEA), reduced vasodilator responses to Ach and cromakalim,
      but not those to nitroprusside. Glibenclamide, an inhibitor of ATP-sensitive K+
      channels, reduced vasodilator responses to cromakalim but did not affect those to
      Ach or nitroprusside. Charybdotoxin, an inhibitor of Ca(++)-activated K+
      channels, reduced vasodilator responses to Ach without affecting those to
      cromakalim or nitroprusside. Iberiotoxin and apamin, inhibitors of large- and
      small-conductance Ca(++)-activated K+ channels, respectively, did not reduce
      vasodilation induced by Ach, cromakalim or nitroprusside. The inhibitor of
      cytochrome P450, clotrimazole, reduced the renal vasodilator effects of Ach and
      bradykinin but not those of nitroprusside or SCA 40, an agonist for Ca(++)
      activated K+ channels. These results suggest that in the rat kidney, Ach, like
      bradykinin, utilizes a charybdotoxin-sensitive Ca(++)-activated K+ channel of
      intermediate conductance to elicit vasodilation and that this effect may be
      dependent on cytochrome P450 activity.

PMID- 9580611
TI  - Spectroscopic studies of nitric oxide (NO) interactions with cobalamins: reaction
      of NO with superoxocobalamin(III) likely accounts for cobalamin reversal of the
      biological effects of NO.
AB  - Recent reports indicate that oxidized cobalamin, Cbl(III), can interfere with the
      biological effects of nitric oxide (NO) on vascular and visceral smooth muscle
      and in other systems. In attempting to elucidate the mechanism of these effects
      of Cbl(III), we reported that a Cbl(III)NO complex could be detected by electron
      paramagnetic resonance (EPR) spectroscopy, but not by ultraviolet/visible
      spectroscopy. Subsequently, others concluded that the alleged Cbl(III)NO complex
      is detectable by ultraviolet/visible, but not by EPR spectroscopy and provided
      ultraviolet/visible evidence for an alleged Cbl(III)NO complex. We report further
      investigation of the interaction of NO with Cbl, using both techniques, Fourier
      transform infrared (FTIR) spectroscopy and mass spectrometry. Our EPR results and
      the UV/VIS results of others appear to be experimental artifacts that can now, at
      least in part, be explained. Under conditions where FTIR measurements readily
      detect a N-O stretching frequency of NO bound to Fe(II), we do not detect a
      similar signal that can be ascribed to either Cbl(III)NO or Cbl(II)NO, indicating
      that neither Cbl(III) nor Cbl(II) form a stable complex with NO. Loss of the
      Cbl(II) EPR signal and mass spectral detection of N2O upon addition of NO to
      Cbl(II) solutions, demonstrates that Cbl(II), which is present in aerobic
      Cbl(III) solutions, reduces NO; however, this reaction does not appear to be fast
      enough to account for the observed biological effects in aerated media. Nitric
      oxide also reacts rapidly and irreversibly with the superoxo complex of Cbl(III),
      Cbl(III)O2-, which is always present in aerated solutions of Cbl(III). We believe
      that this latter reaction accounts for the observed inactivation of NO by
      Cbl(III) in biological systems. Because Cbl(III)O2- is spontaneously regenerated
      from Cbl(II) and O2 in aerated solutions, this may constitute a cyclic mechanism
      for the rapid elimination (oxidation) of NO. Thus, several physicochemical
      techniques fail to provide convincing evidence for the existence of stable
      Cbl(III)NO or Cbl(II)NO complexes but do provide evidence that Cbl species
      participate in redox reactions with NO under aerobic conditions, thereby
      inhibiting its physiological roles.

PMID- 9580612
TI  - Gender difference in the cycle length-dependent QT and potassium currents in
      rabbits.
AB  - Women are known to have a longer electrocardiographic Q-T than men, which may
      contribute to their being at greater risk of developing drug-induced polymorphic
      ventricular arrhythmias. However, little is known about the underlying
      mechanisms. In the present study, we evaluated potential gender differences in Q
      T interval in isolated perfused rabbit hearts using the Langendorff technique and
      evaluated the density of outward potassium currents in single ventricular
      myocytes using the whole-cell patch-clamp technique. We found that female hearts
      demonstrated a greater Q-T lengthening (delta Q-T%) upon an increase in cycle
      length (CL), resulting in a significantly longer Q-T (301 +/- 4.8 ms, CL = 2.3 s)
      at a long CL in female hearts compared with male hearts (267 +/- 4.0 ms, P <
      .01). Ventricular myocytes isolated from female hearts showed a smaller IK(tail)
      and peak IKI outward current density. A 50% reduction in extracellular K+ and
      Mg++ shifted the I-V relationship of IKI and Ito and reduced their amplitude.
      However, neither the I-V relationship of IKr nor the gender difference in the Q-T
      CL relationship was significantly altered. We conclude that 1) female rabbit
      ventricular myocytes have significantly lower IKr and IKl outward current
      densities than do male cells, which may contribute to the gender difference in Q
      T, and 2) a lower base-line IKr density may contribute to the steeper Q-T-CL
      relationship in female hearts.

PMID- 9580613
TI  - Enhancement of gamma-aminobutyric acidA receptor activity by alpha-chloralose.
AB  - alpha-Chloralose is widely used as an anesthetic in the laboratory due to its
      minimal effects on autonomic and cardiovascular systems, yet little is known
      about its mechanism of action. We examined the effects of alpha-chloralose on
      gamma-aminobutyric acid type A (GABAA) receptor activity because recent studies
      have shown that several classes of general anesthetics modulate the function of
      this receptor. GABAA receptor activity was assayed by measuring the GABA-induced
      current in Xenopus oocytes expressed with human GABAA receptor alpha-1, beta-1
      and gamma-2L subunits. alpha-Chloralose produced a concentration-dependent
      potentiation of the GABA-induced current with an EC50 value of 49 microM and a
      maximal effect of 239% of control. Membrane current was not affected by alpha
      chloralose in the absence of GABA. alpha-Chloralose (100 microM) increased the
      affinity for GABA 5-fold and produced a small (17%) increase in the efficacy of
      GABA. Measurement of the reversal potentials for the alpha-chloralose response
      suggested that the effect is mediated through increased Cl- conductance. Studies
      of alpha-chloralose interactions with other allosteric modulators determined that
      alpha-chloralose binds to a site on the GABAA receptor complex distinct from the
      benzodiazepine, neurosteroid and barbiturate sites. Chloral hydrate,
      trichloroethanol and urethane also augmented GABA-induced currents. alpha
      Chloralose had no effect on the hydroxytryptamine-induced currents in oocytes
      expressed with the 5-hydroxytryptamine3 receptor. These data extend the number of
      classes of anesthetics that allosterically modulate GABAA receptor activity and
      indicate that GABAA receptors may be a common site of action for diverse classes
      of general anesthetics.

PMID- 9580614
TI  - Electrophysiological effects of MS-551, a new class III agent: comparison with dl
      sotalol in dogs.
AB  - MS-551 is a newly synthesized, nonspecific K+ channel blocker. To elucidate its
      electrophysiological and potential proarrhythmic effects relative to those of dl
      sotalol in vivo, serial changes in ECGs, endocardial and epicardial monophasic
      action potential durations, and left and right ventricular pressures were
      measured simultaneously in pentobarbital-anesthetized open-chest dogs. Complete
      heart block was produced by the injection of 37% formaldehyde into the
      atrioventricular node. Intravenous administration of MS-551 produced prolongation
      of action potential duration at 90% repolarization time (APD90) immediately after
      the beginning of infusion and reached plateau at 10 min. MS-551 (1 mg/kg) caused
      73 +/- 8% increase in APD90 and 28 +/- 5% increase in QTc at basic cycle length
      of 700 msec. The maximal prolongation of APD90 induced by 1 mg/kg MS-551 was 39%
      greater than that by the same dose of sotalol (P < .01). The dose-response curve
      of prolongation of ventricular effective refractory period produced by MS-551 was
      shifted significantly to the left compared with that induced by sotalol. The EC50
      was 0.5 +/- 0.1 mg/kg and 1.2 +/- 0.2 mg/kg for MS-551 and sotalol, respectively
      (P < .05). When 0.5 mg/kg MS-551 doses were used, no ventricular arrhythmia was
      induced by stimulation at 200-msec basic cycle length. When 1.5 mg/kg sotalol was
      administered, 5 of 15 developed torsade de pointes, 2 of 15 developed ventricular
      fibrillation and 5 of 15 developed sustained ventricular tachycardia. The
      idioventricular rates and left ventricular pressures were reduced significantly
      by sotalol, not by MS-551. In conclusion, MS-551 is a potent class III
      antiarrhythmic agent that selectively prolongs repolarization in the ventricular
      myocardium and appears to be devoid of autonomic effects. Dose for dose, it is
      more potent in prolonging the APD90 and the right ventricular effective
      refractory period possibly with a lower tendency for the development of
      proarrhythmia in a canine heart-block model.

PMID- 9580615
TI  - Potent stimulation of myofilament force and ATPase activity of skeletal muscle by
      eudistomin M, a novel Ca(++)-sensitizing agent from a Caribbean tunicate.
AB  - In the course of our survey of biologically active compounds from natural
      sources, eudistomins were isolated from a Caribbean tunicate Eudistoma olivaceum.
      In the present experiments, eudistomin M (Eud-M, > 10(-5) M) caused a
      concentration-dependent increase in the contractile response of skinned fibers
      from guinea pig skeletal psoas muscles to Ca++. The superprecipitation and ATPase
      activity of myosin B from fast skeletal muscles of rabbit back and leg were
      potentiated by this compound (> 10(-5) M) in a concentration-dependent manner. In
      skinned fibers, superprecipitation and the ATPase activity of myosin B, Eud-M
      shifted the concentration-response curve for Ca++ to the upper direction. Ca(++)
      , K(+)-EDTA- or Mg(++)-ATPase was not affected by Eud-M. This compound had no
      effect on the ATPase activity of actomyosin reconstituted from actin and myosin
      in the presence or absence of troponin. However, the ATPase activity of actin
      myosin-troponin-tropomyosin reconstituted system was increased significantly by
      Eud-M. These results suggest that Eud-M increases the Ca++ sensitivity of the
      contractile apparatus in skeletal muscles at least partially mediated through
      troponin-tropomyosin system and thus enhances the ATPase activity of myosin B and
      the contractile force of myofilament.

PMID- 9580616
TI  - Alterations in corticotropin-releasing factor and vasopressin content in rat
      brain during morphine withdrawal: correlation with hypothalamic noradrenergic
      activity and pituitary-adrenal response.
AB  - The modification in the activity of noradrenergic neurons projecting to the
      hypothalamus and the pituitary-adrenal response during morphine withdrawal as
      well its correlation with alterations in corticotropin-releasing factor (CRF) and
      vasopressin (AVP) content in different brain areas was analyzed. Male rats were
      implanted with placebo (naive) or morphine (tolerant/dependent) pellets for 7
      days. On day 8, groups of rats received an acute injection of saline s.c.
      (control) or naloxone (1 mg/kg s.c.) and were decapitated 30 min later. After
      administration of naloxone to tolerant rats (withdrawal) we found a striking
      parallelism between an enhanced activity of hypothalamic noradrenergic neurons
      and an increased corticosterone secretion; concomitantly, the CRF but not the AVP
      content in the paraventricular nucleus was decreased, which might reflect an
      increased release of the peptide. During withdrawal, CRF content also was
      decreased in the arcuate nucleus, whereas no changes were found in the median
      eminence, dorsomedial, ventromedial nuclei or in the bed nucleus of the stria
      terminalis. AVP content levels were not modified in arcuate nucleus, supraoptic
      or in the suprachiasmatic nuclei. Present data suggest that a hypothalamic
      noradrenergic hypersecretion may be involved in a selectively increased activity
      of CRF neurons in the paraventricular nucleus and arcuate nucleus and then in the
      enhanced release of corticosterone induced by morphine withdrawal. However, we
      did not find any correlation between opioid withdrawal-induced alterations in the
      pituitary-adrenal axis and AVP modifications.

PMID- 9580617
TI  - Effects of kappa-opioid receptor agonists on responses to colorectal distension
      in rats with and without acute colonic inflammation.
AB  - The objective of this study was to evaluate the effects of kappa-opioid receptor
      agonists on pressor and visceromotor responses to colorectal distension in awake,
      unrestrained rats, a model of visceral pain. Because visceral pain can be
      enhanced in the presence of inflammation, the study was conducted in rats that
      had been given either intracolonic saline or 5% acetic acid 6 hr before drug
      administration. We developed a method of staircase colorectal distension as a
      means of obtaining stimulus-response functions over a short period of time. Kappa
      opioid receptor agonists, given i.v. in a cumulative dose paradigm, dose
      dependently attenuated both the pressor and visceromotor responses to colorectal
      distension. In addition, all drugs tested also increased response threshold. The
      rank order of potency of the drugs tested was: CI977 > U69,593 > U50,488 > or =
      morphine > or = EMD61,753 > ICI204,448. Effective doses of these drugs were
      antagonized by naloxone, but not by either of two kappa-opioid receptor-selective
      antagonists (nor-binaltorphimine and 2-(3,4-dichlorophenyl)-N-methyl-N-(1-[3
      isothiocyanate phenyl]-2-[1-pyrrolidinyl]ethyl)-acetamide). Acute inflammation of
      the colon did not lead to changes in the potency of the agonists tested. The
      present results provide further evidence that kappa-opioid receptor agonists
      significantly attenuate visceral nociception and, in conjunction with other
      information, suggest that a peripherally restricted kappa-opioid receptor agonist
      would be therapeutically effective in relieving visceral pain.

PMID- 9580619
TI  - Two new potent neurotransmitter release enhancers, 10,10-bis(4-pyridinylmethyl)
      9(10H)-anthracenone and 10,10-bis(2-fluoro-4-pyridinylmethyl)-9(10H)
      anthracenone: comparison to linopirdine.
AB  - Linopirdine (3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one, DUP996) is an
      extensively studied representative of a class of cognition enhancing compounds
      that increase the evoked release of neurotransmitters. Recent studies suggest
      that these agents act through the blockade of specific K+ channels. We have
      recently identified more potent anthracenone analogs of linopirdine: 10,10-bis(4
      pyridinylmethyl)-9(10H)-anthracenone (XE991) and 10,10-bis(2-fluoro-4
      pyridinylmethyl)-9(10H)-anthracenone (DMP 543). Although linopirdine possesses an
      EC50 of 4.2 microM for enhancement of [3H]ACh release from rat brain slices,
      XE991 and DMP 543 have EC50S of 490 and 700 nM, respectively. In addition to
      greater in vitro potency relative to linopirdine, both compounds show greater in
      vivo potency and duration of action. Although 5 mg/kg (p.o.) linopirdine does not
      lead to statistically significant increases in hippocampal extracellular
      acetylcholine levels, 5 mg/kg (p.o.) XE991 leads to increases (maximal effect >
      90% over baseline) which are sustained for 60 min. Moreover, DMP 543 at 1 mg/kg
      causes more than a 100% increase in acetylcholine levels with the effect lasting
      more than 3 hr. At doses relevant to their release-enhancing properties, the only
      overt symptom consistently observed was tremor, possible via a cholinergic
      mechanism. These results suggest that XE991 and DMP 543 may prove to be superior
      to linopirdine as Alzheimer's disease therapeutics. In addition, these agents
      should be useful pharmacological tools for probing the importance of particular
      ion channels in the control of neurotransmitter release.

PMID- 9580618
TI  - Effects of angiotensin II on intracellular calcium and contracture in
      metabolically inhibited cardiomyocytes.
AB  - Angiotensin II (A-II) is known to potentiate ischemic dysfunction during
      ischemia, but the mechanisms involved are not completely established. We examined
      the effects of A-II on intracellular calcium concentration ([Ca++]i) and cell
      contracture caused by metabolic inhibition in isolated adult rabbit ventricular
      myocytes. [Ca++]i was assessed by flow cytometry, using the Ca(++)-sensitive
      fluorescent probe, fluo-3. After 90 min of exposure to 2 mM cyanide (CN) and 0
      glucose, there was a significant increase in myocyte [Ca++]i. This increase was
      slightly augmented in the presence of 100 nM A-II. In the presence of partial
      Na+/K+ ATP pump inhibition ([K+]o = 0.8 mM), there was a more significant
      increase in [Ca++]i associated with exposure to CN + A-II vs. CN alone. Similar
      results were obtained with CN plus 2-deoxyglucose, and the effect of A-II was
      inhibited by 10 microM 5-(N-ethyl-N-isopropyl)amiloride. Myocytes exposed to 2 mM
      CN and 0 glucose gradually developed contracture over a 3-hr period. Addition of
      100 nM A-II significantly (P < .01) enhanced loss of rod shape morphology during
      3 hr of CN exposure. Partial inhibition of the Na+ pump by exposure to 0.8 mM K+
      had no effect on myocyte survival in the absence of CN, but augmented the harmful
      effect of A-II on cell contracture caused by CN exposure. This effect of A-II was
      completely reversed by the addition of 1 mM amiloride, a Na+/H+ exchange
      inhibitor. We conclude that A-II directly enhances cell injury during CN exposure
      in isolated rabbit ventricular myocytes. We postulate that this effect of A-II is
      mediated by stimulation of Na+/H+ exchange with resultant increased [Na+]i and
      subsequent [Ca++]i loading, possibly via reverse Na+/Ca++ exchange.

PMID- 9580620
TI  - Modulation of the neuronal nicotinic acetylcholine receptor-channel by the
      nitromethylene heterocycle imidacloprid.
AB  - Nitromethylene heterocycle insecticides are known to act on the nicotinic
      acetylcholine receptor-channel. The effects of the nitromethylene heterocycle,
      imidacloprid, on the nicotinic acetylcholine receptor-channel of clonal rat
      phaeochromocytoma (PC12) cells were studied using whole-cell and single-channel
      patch clamp methods. Imidacloprid suppressed carbachol-induced whole-cell
      currents in a dose-dependent manner, and this compound itself generated small
      currents. Multiple conductance states of single-channel currents were also evoked
      by imidacloprid at the nicotinic acetylcholine receptor-channels. The most
      frequently generated single-channel currents showed two conductance states, 25.4
      and 9.8 pS, which were identical to the conductance states of acetylcholine
      generated currents. The mean open time and burst duration of the main conductance
      currents induced by imidacloprid were shorter than those induced by
      acetylcholine. Co-application of imidacloprid and acetylcholine caused some
      interactions at the two conductance states. Mean open time and mean burst
      duration of the main conductance state currents evoked by acetylcholine were
      decreased by the co-application of imidacloprid as compared with those induced by
      acetylcholine alone. In conclusion, imidacloprid has both multiple agonist and
      antagonist effects on the neuronal nicotinic acetylcholine receptor-channels.

PMID- 9580622
TI  - Short-term hemodynamic effects of mibefradil in dogs with chronic heart failure:
      comparison with diltiazem.
AB  - Despite the marked vasodilator and antiischemic actions of existing calcium
      channel blockers, their use in the treatment of patients with chronic heart
      failure (HF) remains highly controversial. We compared the short-term hemodynamic
      effects of i.v. mibefradil, a predominant T-type calcium channel blocker with
      only partial L-type calcium channel antagonism, and diltiazem, a selective L-type
      calcium channel antagonist in dogs with chronic HF. Each of three drugs namely,
      mibefradil, diltiazem and normal saline (as placebo control), were studied in
      random order (6 days between each drug intervention), in each of 8 dogs with
      chronic HF produced by multiple intracoronary microembolizations. Intravenous
      mibefradil and diltiazem were administered as a 100 micrograms/kg bolus followed
      by a continuous infusion of 6 and 4 micrograms/kg/min, respectively, for 15 min.
      Equal volumes of normal saline were administered in an identical fashion. In all
      instances, hemodynamics were obtained at base line and at 5, 10, 15, 30 and 60
      min after bolus drug administration. Left ventriculograms were obtained at
      baseline, and at 15 and 60 min after bolus drug administration. Saline infusion
      had no effects on hemodynamic or angiographic indexes of left ventricular (LV)
      function. At 15 min, mibefradil caused significant increases of LV stroke volume
      and LV ejection fraction compared to baseline (40 +/- 5 vs. 31 +/- 3 ml, P < .05
      and 41 +/- 1 vs. 28 +/- 1%, P < .05, respectively). In contrast, at 15 min,
      diltiazem produced no significant changes of LV stroke volume or ejection
      fraction compared to baseline despite reducing mean aortic pressure to the same
      extent as mibefradil. Short-term i.v. mibefradil improves LV function in dogs
      with chronic HF. The beneficial effects of mibefradil compared to diltiazem may
      be a consequence of T-type calcium channel selectivity resulting in a
      vasodilatory response that is free of negative inotropy.

PMID- 9580621
TI  - Effects of three sarcoplasmic/endoplasmic reticulum Ca++ pump inhibitors on
      release channels of intracellular stores.
AB  - The three principal sarcoplasmic/endoplasmic reticulum Ca++ pump inhibitors have
      been compared for their effects on Ca++ fluxes across intracellular stores
      present in isolated skeletal muscle and brain membrane preparations. At moderate
      concentrations that only partially inhibited Ca++ pumping, all three inhibitors
      induced transient release of Ca++ from isolated sarcoplasmic reticulum membranes,
      and release was ruthenium red-sensitive, much faster and sustained at higher pump
      inhibitor concentrations. In contrast, in unidirectional 45Ca efflux assays,
      cyclopiazonic acid appeared to have little effect, thapsigargin decreased efflux
      and 2,5-di(tert-butyl)-1,4-benzohydroquinone increased efflux only slightly.
      These observations taken together suggest that transient releases were manifest
      primarily by vesicles with a high ratio of ryanodine receptors to pumps (and thus
      more susceptible to becoming leaky with only some pumps inhibited), and that
      Ca(++)-induced Ca++ release amplified releases when all pumps were blocked. These
      mostly indirect side effects were specific for ryanodine receptors. In similar
      experiments with brain cerebellar membranes, none of the three inhibitors
      appeared to directly reduce release induced by inositol 1,4,5-trisphosphate.
      These findings may affect interpretation of results of experiments involving
      application of these compounds to isolated membranes, cells or tissue
      preparations.

PMID- 9580623
TI  - Stabilization of vasoactive intestinal peptide by lipids.
AB  - An anionic phospholipid, phosphatidylglycerol (PG), induced vasoactive intestinal
      peptide (VIP) to adopt a helical conformation, determined by circular dichroism
      studies. PG inhibited the trypsin-catalyzed, antibody-catalyzed and uncatalyzed
      cleavage of VIP, measured by radiometric and HPLC methods. Phosphatidylcholine, a
      neutral lipid, did not alter the circular dichroism spectra of VIP, and it was
      without detectable effect on the rates of VIP cleavage. Trypsin-catalyzed
      cleavage of Boc-Ile-Glu-Arg-methylcoumarinamide, a substrate unrelated in
      sequence to VIP, proceeded at equivalent rates in the absence and presence of PG,
      which suggests that the phospholipid did not exert a nonspecific inhibitory
      effect on the enzyme. Study of the kinetics of antibody-catalyzed VIP cleavage
      indicated that the inhibition by PG was due to decreased affinity for VIP,
      suggested by observations of increased K(m) values and unaltered Vmax values.
      Incorporation of VIP in the liposomes and the liposomal surface permitted
      maintenance of the peptide in essentially undegraded form at 37 degrees C for 8
      days. The longevity of liposomal VIP administered i.v. to mice was increased by
      about 5-fold compared with aqueous VIP. These observations indicate that certain
      phospholipids and liposomes can be applied to circumvent the rapid loss of VIP in
      vitro and in vivo due to degradative processes.

PMID- 9580624
TI  - Coupling of store-operated Ca++ entry to contraction in rat aorta.
AB  - The purpose of this study was to test whether the elevated intracellular Ca++
      level ([Ca++]i) resulting from store-operated Ca++ entry was associated with
      vascular smooth muscle contraction. Cyclopiazonic acid (CPA), a selective
      inhibitor of sarcoplasmic reticulum Ca(++)-ATPase, concentration-dependently (1
      10 microM) elevated [Ca++]i in rat aorta, as indicated by an increase in the fura
      2 340/380 ratio. Simultaneous measurement of contraction demonstrated that 1 and
      10 microM CPA induced insignificant and variable amounts of contraction,
      respectively. Verapamil (10 microM) had relatively little effect on the 1 and 10
      microM CPA-elevated [Ca++]i. In contrast, Ni++ (0.1 mM), in the presence of
      verapamil, abolished the 1 microM CPA-elevated [Ca++]i. Ni++ (0.1 mM) also
      partially decreased the 10 microM CPA-elevated [Ca++]i and, furthermore,
      abolished the associated contraction. A higher Ni++ concentration (1 mM)
      abolished the 10 microM CPA-elevated [Ca++]i that remained after verapamil and
      0.1 mM Ni++. Phorbol dibutyrate (10 nM), a protein kinase C activator,
      potentiated contractions to 1 and 10 microM CPA in the presence of verapamil.
      Ni++ (0.1 mM) abolished the enhanced contractions, and decreased the elevated
      [Ca++]i. These results suggest that 1) elevated [Ca++]i due to store-operated
      Ca++ entry is dissociated from contraction; 2) the elevated [Ca++]i is restricted
      to at least two noncontractile compartments that can be differentiated by their
      relative sensitivities to blockade by low (0.1 mM) and higher (1 mM) Ni++
      concentrations, and 3) [Ca++]i elevation within the compartment sensitive to
      blockade by 0.1 mM Ni++ can be coupled to contraction via protein kinase C
      activation.

PMID- 9580625
TI  - N-methyl-D-aspartate receptor channel block by the enantiomeric 6,7-benzomorphans
      BIII 277 CL and BIII 281 CL.
AB  - BIII 277 CL ((-)-2R-[2 alpha, 3(R*),6 alpha]-3-(2-methoxypropyl)-6,11, 11
      trimethyl-2,6-methano-1,2,3,4,5,6-hexahydro-3-benzazocin-9-ol hydrochloride) is a
      novel benzomorphan with neuroprotective and anticonvulsant properties that
      exhibits high affinity binding to the N-methyl-D-aspartate (NMDA) receptor but,
      in contrast to other structurally related benzomorphans, low affinity for mu
      opiate and sigma sites. Whole-cell voltage-clamp and single-channel recording
      were used to study the interaction of BIII 277 CL and its enantiomer BIII 281 CL
      with native NMDA receptors in cultured hippocampal neurons. BIII 277 CL and BIII
      281 CL produced a slow use-dependent block of whole-cell NMDA receptor currents.
      Once block was established, recovery was slow (< 50% in > or = 40 min). The
      steady-state IC50 (nH) values derived from logistic fits to concentration-block
      isotherms obtained at -60 mV were 5.3 nM (0.67) and 58 nM (1.2), respectively.
      The benzomorphans had no effect on currents evoked by alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionate and gamma-aminobutyric acid but minimally inhibited
      kainate-evoked currents at high (> or = 30 microM) concentrations. BIII 277 CL
      and BIII 281 CL failed to bind and block closed NMDA receptor channels, and the
      block was occluded by Mg++, consistent with an open channel-blocking mechanism.
      Steady-state block was diminished by depolarization; analysis of the voltage
      dependence of block indicated that BIII 281 CL binds within the channel at a site
      that senses 46% of the transmembrane electric field. Recordings of single NMDA
      receptor channels in outside-out membrane patches confirmed the slow, persistent
      blocking action obtained in whole-cell recordings. In addition, at high
      concentrations, flickering of the unitary currents was observed consistent with a
      low-affinity channel-blocking action. Taking the present data in conjunction with
      previously obtained structure-activity information for N-substituted
      benzomorphans, a three-mode-blocking model was developed in which there are three
      interaction sites for binding of the high-affinity ligand BIII 277 CL. In this
      model, the drug can bind in one of three modes by docking at one, two or all
      three interaction points but cannot transition between modes. The model further
      proposes that the lower-affinity enantiomer BIII 281 CL binds in modes with one
      and two but not all three interaction points docked. We conclude that BIII 277 CL
      and BIII 281 CL are potent and selective, use-dependent (uncompetitive) channel
      blocking NMDA receptor antagonists. The substantially higher affinity that BIII
      277 CL exhibits for the NMDA receptor in comparison with its enantiomer and other
      benzomorphans appears to be due to stabilization of binding at three sites within
      the channel.

PMID- 9580626
TI  - ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective
      analgesic acting via neuronal nicotinic acetylcholine receptors: I. In vitro
      characterization.
AB  - The discovery of (+/-)-epibatidine, a naturally occurring neuronal nicotinic
      acetylcholine receptor (nAChR) agonist with antinociceptive activity 200-fold
      more potent than that of morphine, has renewed interest in the potential role of
      nAChRs in pain processing. However, (+/-)-epibatidine has significant side-effect
      liabilities associated with potent activity at the ganglionic and neuromuscular
      junction nAChR subtypes which limit its potential as a clinical entity. ABT-594
      [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine] is a novel, potent cholinergic
      nAChR ligand with analgesic properties (see accompanying paper by Bannon et al.,
      1998b) that shows preferential selectivity for neuronal nAChRs and a consequently
      improved in vivo side-effect profile compared with (+/-)-epibatidine. ABT-594 is
      a potent inhibitor of the binding of [3H](-)-cytisine to alpha 4 beta 2 neuronal
      nAChRs (Ki = 37 pM, rat brain; Ki = 55 pM, transfected human receptor). At the
      alpha 1 beta 1 delta gamma neuromuscular nAChR labeled by [125I] alpha
      bungarotoxin (alpha-Btx), ABT-594 has a Ki value of 10,000 nM resulting in a
      greater than 180,000-fold selectivity of the compound for the neuronal alpha 4
      beta 2 nAChR. In contrast, (+/-)-epibatidine has Ki values of 70 pM and 2.7 nM at
      the alpha 4 beta 2 and alpha 1 beta 1 delta gamma nAChRs, respectively, giving a
      selectivity of only 38-fold. The S-enantiomer of ABT-594, A-98593 has activity at
      the neuronal alpha 4 beta 2 nAChR identical with ABT-594 (Ki = 34-39 pM), which
      demonstrates a lack of stereospecific binding similar to that reported previously
      for (+/-)-epibatidine. A similar lack of stereoselectivity is seen at the human
      alpha 7 receptor. However, A-98593 is 3-fold more potent at the neuromuscular
      nAChR (Ki = 3420 nM) and the brain alpha-Btx-sensitive nAChR (Ki = 4620 nM) than
      ABT-594. ABT-594 has weak affinity in binding assays for adrenoreceptor subtypes
      alpha-1B (Ki = 890 nM), alpha-2B (Ki = 597 nM) and alpha-2C (Ki = 342 nM), and it
      has negligible affinity (Ki > 1000 nM) for approximately 70 other receptors,
      enzyme and transporter binding sites. Functionally, ABT-594 is an agonist. At the
      transfected human alpha 4 beta 2 neuronal nAChR (K177 cells), with increased
      86Rb+ efflux as a measure of cation efflux, ABT-594 had an EC50 value of 140 nM
      with an intrinsic activity (IA) compared with (-)-nicotine of 130%; at the nAChR
      subtype expressed in IMR-32 cells (sympathetic ganglion-like), an EC50 of 340 nM
      (IA = 126%); at the F11 dorsal root ganglion cell line (sensory ganglion-like),
      an EC50 of 1220 nM (IA = 71%); and via direct measurement of ion currents, an
      EC50 value of 56,000 nM (IA = 83%) at the human alpha 7 homooligimeric nAChR
      produced in oocytes. A-98593 is 2- to 3-fold more potent and displays
      approximately 50% greater intrinsic activity than ABT-594 in all four functional
      assays. In terms of potency, ABT-594 is 8- to 64-fold less active than (+/-)
      epibatidine and also has less IA in these functional assays. ABT-594 (30 microM)
      inhibits the release of calcitonin gene-related peptide from C-fibers terminating
      in the dorsal horn of the spinal cord, an effect mediated via nAChRs.
      Pharmacologically, ABT-594 has an in vitro profile distinct from that of the
      prototypic nicotinic analgesic (+/-)-epibatidine, with the potential for
      substantially reduced side-effect liability and, as such, represents a
      potentially novel therapeutic approach to pain management.

PMID- 9580628
TI  - Pharmacokinetic analysis for assessing developmental toxicity of a new synthetic
      acetolactate synthase inhibitor, LGC-40863, in rats.
AB  - Effects of O-[2,6-bis[(4,6-dimethoxy-2pyrimidinyl)oxy]benzoyl]oxime (LGC-40863)
      on dams and embryonic development were examined at p.o. doses of 500, 1000 and
      2000 mg/kg/day on days 6 to 15 of gestation in rats. No significant maternal or
      embryonic toxicity was observed at any of the doses. However, external fetal
      anomalies including brachycephaly, microcephaly, micrognathia, agnathia, lordosis
      and edema were observed at an incidence of 2.2% at the lowest dosage level but
      not at higher dosages. Because these malformations are not common as spontaneous
      variations in rats, we carried out a toxicokinetic study to clarify whether the
      fetal anomalies at 500 mg/kg are related to LGC-40863. During multiple p.o.
      administrations of LGC-40863 at the same doses used in the developmental toxicity
      study, LGC-40863 was not detected in the systemic circulation. Moreover, 3 months
      of multiple dosing did not alter its plasma level. In the pregnant rats receiving
      500 mg/kg on 10 consecutive days of gestation, LGC-40863 was also undetectable.
      However, after i.v. administration, high levels of the drug were found in plasma,
      and these could be described by a two-compartment model. These results
      demonstrate that the bioavailability of LGC-40863 is negligible. To investigate a
      possible relevance of metabolite(s) to the fetal anomalies, we examined excretion
      of radioactivity after p.o. doses of 500 and 2000 mg/kg of LGC-40863 spiked with
      [14C]LGC-40863. For both doses, cumulative recovery up to 72 hr was approximately
      80% and 9% in feces and urine, respectively, indicating dose linearity in the
      elimination kinetics. Overall, these toxicokinetic data suggest that the fetal
      anomalies observed at 500 mg/kg are not associated with LGC-40863 but are
      spontaneously generated. In conclusion, LGC-40863 had neither significant
      maternal nor developmental toxicity at any of the doses tested for p.o. exposure.

PMID- 9580627
TI  - ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective
      antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II.
      In vivo characterization.
AB  - The antinociceptive effects of ABT-594, a novel nicotinic acetylcholine receptor
      (nAChR) ligand, were examined in rats in models of acute thermal (hot box) and
      persistent chemical (formalin test) pain. Also, the effects of ABT-594 treatment
      on motor function and electroencephalogram (EEG) were determined. In the hot box
      and formalin test (i.e., phase 1 and 2), acute treatment with ABT-594 (0.03, 0.1
      and 0.3 mumol/kg i.p.) produced significant dose-dependent antinociceptive
      effects. In the hot box, the efficacy of ABT-594 was maintained after a repeated
      dosing paradigm (5 days b.i.d.i.p.). ABT-594 was fully efficacious in the
      formalin test when administered before formalin, and also retained significant
      efficacy (0.3 mumol/kg i.p.) when administered after formalin injection. The
      antinociceptive effects of ABT-594 in the hot box and formalin tests were
      attenuated by pretreatment with the nAChR antagonist, mecamylamine, and in
      animals treated with the nAChR antagonist chlorisondamine, given centrally (10
      micrograms/rat i.c.v. 5 days before), but not in animals pretreated with the
      opioid receptor antagonist, naltrexone. Acute treatment with ABT-594 produced an
      initial decrease in open-field locomotor activity, which was absent in animals
      dosed repeatedly (5 days b.i.d.) with ABT-594. Also, acute treatment with ABT-594
      decreased body temperature and decreased the amount of time the animals could
      maintain balance in an edge-balance test. These effects were no longer present in
      animals dosed repeatedly with ABT-594. At antinociceptive doses, ABT-594 produced
      activation of free running EEG in contrast to the sedative-like effects of
      morphine. Full antinociceptive efficacy was maintained in both the hot box and
      formalin tests after oral administration, whereas the effects on motoric
      performance were attenuated. In conclusion, these data demonstrate that ABT-594
      is a potent antinociceptive agent with full efficacy in models of acute and
      persistent pain and that these effects are mediated predominately by an action at
      central neuronal nAChRs. In addition, antinociceptive effects were maintained
      after repeated dosing, whereas effects of ABT-594 on motor and temperature
      measures were attenuated in animals treated repeatedly with ABT-594. Thus,
      compounds acting at nAChRs may represent a novel approach for the treatment of a
      variety of pain states.

PMID- 9580629
TI  - Modulation of mouse endotoxin shock by inhibition of phosphatidylcholine-specific
      phospholipase C.
AB  - During Gram-negative bacterial infections, lipopolysaccharide (LPS) interacts
      with monocyte/macrophage receptors, resulting in a host defense response.
      Activation of intracellular signal transduction pathways implicating various
      protein kinase and phospholipases is crucial in activating the transcription of
      genes encoding proinflammatory cytokines and inducible nitric oxide synthase
      (iNOS). In this article, we demonstrate that in mouse, endotoxin shock activation
      of phosphatidylcholine-specific phospholipase C (PC-PLC) plays a major role in
      controlling the inflammatory response. Inhibition of PC-PLC by the specific
      inhibitor tricyclodecan-9-yl-xanthogenate (D609) before LPS reduced the release
      of interleukin-1 beta, interleukin-6 and nitric oxide (NO) in vivo. In contrast,
      tumor necrosis factor-alpha serum levels were not altered by the pretreatment
      with D609. Consequently, survival from endotoxin shock of D609-treated animals
      was significantly improved compared with control animals (45% vs. 20%). Thus,
      inhibition of PC-PLC can reduce the inflammatory response to LPS and may serve as
      a novel approach to therapy of sepsis.

PMID- 9580630
TI  - 5-Hydroxytryptamine2 receptor facilitates GABAergic neurotransmission in rat
      hippocampus.
AB  - 5-Hydroxytryptamine (5-HT; serotonin) administration enhances GABAergic synaptic
      activity recorded in pyramidal neurons of the CA1 region of hippocampus. Previous
      studies have attributed this effect to the activation of HT-5(3) receptors
      located on GABAergic interneurons. During unrelated experiments, we noticed that
      under our recording conditions, 5-HT can still increase GABAergic synaptic
      activity after the complete blockade of 5-HT3 receptors. This indicated the
      involvement of an additional 5-HT receptor subtype. Therefore, we reinvestigated
      the effects of 5-HT on GABAergic synaptic activity recorded in pyramidal cells of
      the CA1 region. The ability of 5-HT to increase GABAergic synaptic activity in
      the presence of 5-HT3 receptor blockade was mimicked by the selective 5-HT2
      agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and blocked by the
      selective 5-HT2 antagonist ketanserin. This indicated that the additional 5-HT
      receptor belongs to 5-HT2 receptor family. 5-HT2 receptor activation resulted in
      an increase in the frequency of spontaneous inhibitory postsynaptic currents as
      well as a shift in their amplitude distribution toward larger sizes. These
      effects were absent in the presence of tetrodotoxin. We interpret these results
      to indicate that 5-HT2 receptors activate GABAergic interneurons in the slice,
      leading to an increase in GABAergic synaptic activity onto pyramidal cells of the
      CA1 region.

PMID- 9580631
TI  - Cannabinoid-precipitated withdrawal: a time-course study of the behavioral aspect
      and its correlation with cannabinoid receptors and G protein expression.
AB  - To characterize the time course of the behavioral and biochemical aspects of the
      cannabinoid withdrawal syndrome, we injected the cannabinoid antagonist SR141716A
      (5 mg/kg i.p.) in rats made tolerant to CP-55,940 (0.4 mg/kg i.p., twice daily
      for 6.5 days), 1, 24 and 96 h after the last CP-55,940 injection. Because the CB1
      receptor and G protein alpha subunit are involved in cannabinoid tolerance, we
      observed their changes throughout the brain during the withdrawal syndrome by use
      of in situ hybridization. In vehicle-pretreated rats SR141716A per se induced
      abnormal behavior significantly different from the vehicle group: wet dog shakes,
      forepaw fluttering and scratching. These signs remained significantly elevated
      even after the second and third antagonist doses. SR141716A significantly
      modified the mRNA levels of G alpha s and G alpha i subunits in some brain areas
      without affecting CB1 receptor and G alpha o expression. These findings led us to
      conclude that SR141716A may have intrinsic activity. Concerning cannabinoid
      withdrawal, the first SR141716A injection in tolerant rats resulted in behavioral
      signs different from those observed with the antagonist alone; this moderate
      withdrawal syndrome was characterized by turning, chewing and digging. Additional
      SR141716A doses 24 and 96 h later did not induce a significant abstinence
      syndrome. In situ hybridization after the first SR141716A injection showed that
      CB1 receptor and G protein alpha subunits, whose levels were low in tolerance,
      recovered their basal level of expression. Thus, the general desensitization of
      the cannabinoid receptor and of the transduction system in tolerance are
      recovered in abstinent rats and might be part of the molecular mechanisms
      underlying cannabinoid dependence.

PMID- 9580632
TI  - delta Opioid receptor subtypes activate inositol-signaling pathways in the
      production of antinociception.
AB  - To analyze the selectivity of delta receptor subtypes to regulate different
      classes of G proteins, the expression of the alpha-subunits of Gi2, Gi3, Go1,
      Go2, Gq and G11 transducer proteins was reduced by administration of
      oligodeoxynucleotides (ODNs) complementary to sequences in their respective
      mRNAs. Mice receiving antisense ODNs to Gi2 alpha, Gi3 alpha, Go2 alpha and G11
      alpha subunits showed an impaired antinociceptive response to all the delta
      agonists evaluated. An ODN to Go1 alpha specifically blocked the antinociceptive
      effect of the agonist of delta-1 receptors, [D-Pen2,5]enkephalin (DPDPE), without
      altering the activity of [D-Ala2]deltorphin II or [D-Ser2]-Leu-enkephalin-Thr
      (DSLET). In mice treated with an ODN to Gq alpha, the effects of the agonists of
      delta-2-opioid receptors were reduced, but not those of DPDPE. Thus, Go1 proteins
      are selectively linked to delta-1-mediated analgesia, and Gq proteins are related
      to delta-2-evoked antinociception. After impairing the synthesis of Go1 alpha
      subunits, DPDPE exhibited an antagonistic activity on the antinociception
      produced by [D-Ala2]deltorphin II. After treatment with ODNs complementary to
      sequences in Gq alpha or PLC-beta 1 mRNAs, the analgesic capacity of [D
      Ala2]deltorphin II was diminished. However, the delta-2-agonist did not alter the
      antinociceptive activity of DPDPE. An ODN complementary to nucleotides 7 to 26 of
      the murine delta receptor reduced the analgesic potency of [D-Ala2]deltorphin II,
      but not that observed for DPDPE. In these mice, [D-Ala2]deltorphin II did not
      antagonize the effect of DPDPE. These results suggest the existence of different
      molecular forms of the delta opioid receptor, and the involvement of inositol
      signaling pathways in the supraspinal antinociceptive effects of delta agonists.

PMID- 9580633
TI  - Guanine nucleotide-binding inhibitory protein-mediated inhibition of adenylyl
      cyclase is enhanced in spontaneously hypertensive rat preglomerular arteriolar
      smooth muscle cells.
AB  - The purpose of our study was to determine whether Gi-mediated control over
      adenylyl cyclase in preglomerular arteriolar smooth muscle cells (PGASMC) is
      enhanced in the spontaneously hypertensive rat (SHR). PGASMC were cultured from
      preglomerular microvessels isolated from adult SHR (14-15 wk of age) and age
      matched WKY rats. Confluent monolayers of cells in third passage were used for
      the experiments. cAMP released into the media (30 min) as well as cellular levels
      of cAMP were measured in the presence of a phosphodiesterase inhibitor, 1
      isobutyl-3-methyl-xanthine (IBMX; 100 microM) and expressed as pmol/mg protein.
      Total (released + cellular) cAMP was significantly lower in SHR (14.19 +/- 2.30
      pmol/mg protein) as compared with WKY (28.3 +/- 3.04 pmol/mg protein).
      Correspondingly, the released (4.6 +/- 0.4 pmol/mg protein) as well as cellular
      (9.78 +/- 2.18 pmol/mg protein) cAMP levels were also significantly lower in SHR
      when compared with WKY (8.85 +/- 1.26 and 18.86 +/- 2.0 pmol/mg protein,
      respectively). The steady-state levels of none of the Gi alpha subunits, namely
      Gi alpha 1, Gi alpha 2 and Gi alpha 3, were higher in the SHR PGASMC. Pertussis
      toxin treatment (PTX; 100 ng/ml; 24 hr) caused complete ADP-ribosylation of Gi
      alpha subunits in both WKY and SHR PGASMC. The same treatment of PTX also
      produced a significant increase in total cAMP in SHR, but not in WKY, such that
      the total cAMP levels after PTX treatment were not significantly different
      between the two strains. Interestingly, PTX significantly increased the released
      (20.26 +/- 0.90 pmol/mg protein) but not the cellular (13.63 +/- 1.63 pmol/mg
      protein) cAMP in SHR. Forskolin (1 microM) induced similar increases in total
      cAMP and isoproterenol (1 microM) caused greater increases in total cAMP in SHR
      cells compared with WKY cells. These data strongly suggest that in SHR PGASMC
      total adenylyl cyclase activity is not altered. Furthermore, steady-state
      expressions of Gi alpha-1, Gi alpha-2 and Gi alpha-3 are not increased whereas Gi
      mediated inhibition of adenylyl cyclase is augmented in SHR PGASMC.

PMID- 9580634
TI  - Regulation of the Na+/K(+)-ATPase pump in vitro after long-term exposure to
      cocaine: role of serotonin.
AB  - Long-term exposure to cocaine can cause persistent behavioral changes and
      alterations in neuronal function. One cocaine-regulated mRNA in the rat brain is
      the beta-1 subunit of the Na+/K(+)-ATPase pump. We examined both Na+/K(+)-ATPase
      function and expression after cocaine treatment of pheochromocytoma cells. One
      hour exposure to cocaine did not alter Na+/K(+)-ATPase activity, as measured by
      the ouabain-sensitive component of rubidium uptake. Four days of cocaine resulted
      in an approximately 30% decrease in Na+/K(+)-ATPase activity. Western blot
      analyses demonstrated an approximately 25% decrease in levels of the beta-1
      isoform, without changes in pump total alpha subunit levels. Treatment with
      dopamine type 1 or type 2 receptor agonists for the same period did not affect
      Na+/K(+)-ATPase activity. The serotonin-selective reuptake inhibitor paroxetine
      caused an approximately 45% decrease in rubidium uptake after 4 days, whereas
      pump function was not altered after treatment with either the dopamine-selective
      reuptake blocker nomifensine or the norepinephrine-selective reuptake blocker
      desipramine. Chronic treatment with both cocaine and LY 278,584, a serotonin type
      3 receptor antagonist, did not replicate the cocaine-associated decrease in pump
      function. Long-term cocaine exposure regulates expression and function of the
      Na+/K(+)-ATPase pump in neuronal-like cells; this regulation is mediated in part
      via the serotonin type 3 receptor. Similar Na+/K(+)-ATPase pump regulation in
      vivo may selectively alter neuronal function in the mammalian brain.

PMID- 9580635
TI  - Inhibition of platelet-derived growth factor and epidermal growth factor receptor
      signaling events after treatment of cells with specific synthetic inhibitors of
      tyrosine kinase phosphorylation.
AB  - The receptor kinase activity associated with the epidermal growth factor (EGF)
      receptor and platelet-derived growth factor (PDGF) receptor plays an important
      role in ligand-induced signaling events. The effect of specific, synthetic
      chemical inhibitors of PDGF- and EGF-mediated receptor tyrosine
      autophosphorylation on receptor signaling were examined in NIH 3T3 cells
      overexpressing PDGF or EGF receptors. Specific inhibition of ligand-dependent
      receptor autophosphorylation, PI3K activation, mitogen-activated protein kinase
      (MAPK) activation, cyclin E-associated kinase activity and cell proliferation was
      measured after treatment of cells with these inhibitors. A synthetic PDGF
      receptor kinase inhibitor exhibited specific inhibitory properties when tested
      for PDGF-induced receptor autophosphorylation, MAPK activity, PI3K activation,
      entry into S phase and cyclin E-associated kinase activity. A synthetic EGF
      receptor kinase inhibitor showed selective inhibitor properties when tested for
      EGF-induced receptor autophosphorylation, MAPK activation, PI3K activation, entry
      into S phase and cyclin E-associated kinase activity. In both cases, these
      compounds were found to be effective as inducers of growth arrest and
      accumulation of cells in the G1 phase of the cell cycle after ligand treatment.
      However, at high concentrations, the EGF receptor kinase inhibitor was observed
      to exhibit some nonspecific effects as demonstrated by attenuation of PDGF
      induced receptor autophosphorylation and cell cycle progression. This
      demonstrates that it is critical to use the lowest concentration of such an
      inhibitor that will alter the response under investigation, to have confidence
      that the conclusions derived from the use of such inhibitor are valid. We
      conclude that these experimental parameters signify useful end points to measure
      the relative selectivity of tyrosine kinase inhibitors that affect receptor
      mediated signal transduction.

PMID- 9580637
TI  - Tyrosine phosphatase-dependent/tyrosine kinase-independent induction of nuclear
      factor-kappa B by tumor necrosis factor-alpha: effects on prostaglandin
      endoperoxide synthase-2 mRNA accumulation.
AB  - We previously have demonstrated that tumor necrosis factor-alpha (TNF-alpha)
      increases prostaglandin endoperoxide synthase-2 (PGHS-2) mRNA accumulation and
      tyrosine phosphorylation in the fibrosarcoma cell line, MCA-101. Tyrosine kinase
      inhibitor, genistein, and tyrosine phosphatase inhibitor, phenylarsine oxide
      (PAO), blocked TNF-alpha-mediated induction of PGHS-2 mRNA in these cells.
      Because the PGHS-2 promoter has a nuclear factor-kappa B (NF-kappa B) binding
      motif, which is important for PGHS-2 gene transcription in some cell types, we
      have evaluated the effects of tyrosine kinase inhibitors and PAO on TNF-alpha
      induced NF-kappa B activation. TNF-alpha (1 nM) rapidly induced translocation of
      NF-kappa B, an event accompanied by degradation of inhibitory protein I kappa B
      alpha. N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a serine protease
      inhibitor, inhibited I kappa B-alpha degradation and NF-kappa B activation in
      response to TNF-alpha in a dose-dependent manner (25, 50, 100 microM). TPCK also
      inhibited PGHS-2 mRNA accumulation. These data suggest that NF-kappa B
      contributed to PGHS-2 mRNA accumulation in MCA-101 cells stimulated with TNF
      alpha. PAO (2.4 microM) completely abolished activation of NF-kappa B and
      degradation of I kappa B-alpha induced by TNF-alpha at a concentration that
      blocked PGHS-2 mRNA accumulation. However, four tyrosine kinase inhibitors,
      genistein, tyrphostin 47, herbimycin A and erbstatin, failed to block
      translocation of NF-kappa B and degradation of I kappa B-alpha. These data
      demonstrate that tyrosine kinase pathways are not required for TNF-alpha-induced
      NF-kappa B activation in MCA-101 cells and suggest that signaling via these
      pathways mediates TNF-alpha-induced PGHS-2 mRNA accumulation via an NF-kappa B
      independent mechanism. Moreover, an upstream tyrosine phosphatase pathway may
      mediate PGHS-2 mRNA accumulation by TNF-alpha via an NF-kappa B-dependent
      mechanism.

PMID- 9580636
TI  - Pharmacological and molecular characterization of muscarinic receptors in cat
      esophageal smooth muscle.
AB  - The muscarinic receptor subtypes that mediate cholinergic responses in cat
      esophageal smooth muscle were examined. Antagonist effects on carbachol-induced
      and nerve-evoked contractions were studied in vitro using muscle strips from the
      distal esophagus. Antagonists displayed similar relative selectivities in
      suppressing carbachol and nerve-mediated responses as follows: 4-diphenylacetoxy
      N-methylpiperidine (4-DAMP) > zamifenacin > para-fluoro-hexahydrosiladiphenidol >
      pirenzepine > AF-DX 116 > methoctramine, indicating that these responses are
      mediated by the same receptor subtype. 4-DAMP, pirenzepine and methoctramine
      effects on carbachol responses gave pA2 values characteristic of the M3 receptor
      in both the circular muscle (9.25 +/- 0.12, 6.79 +/- 0.09 and 6.04 +/- 0.11,
      respectively) and longitudinal muscle (9.46 +/- 0.14, 7.25 +/- 0.07 and 6.10 +/-
      0.06, respectively). Reverse transcription-polymerase chain reaction analysis was
      done using primer sequences based on the cloned human muscarinic receptor
      subtypes. Messenger RNA for the m3 receptor was readily identified, whereas m2
      was not detected in esophageal muscle, but was present in cardiac muscle.
      Sequence homology between the amplified products from cat tissue and the
      corresponding human m2 and m3 receptors genes were 93% and 89%, respectively. In
      the cat esophagus, the M3 receptor mediates functional responses and messenger
      RNA for the corresponding molecular form of this receptor is abundant in this
      tissue.

PMID- 9580638
TI  - Colitis-induced changes in the expression of the Na+/H+ exchanger isoform NHE-1.
AB  - The sodium hydrogen exchanger (NHE) plays an important role in the absorption of
      NaCl, the regulation of intracellular pH and cell growth. These functions are
      compromised in the inflammatory bowel diseases. The objective of this study was
      to examine the expression of the NHE-1 isoform during colitis induced by acetic
      acid or trinitrobenzenesulfonic acid in Sprague-Dawley male rats. We also
      examined the effect of dexamethasone on the expression of NHE-1. Levels of mRNA
      were estimated using the reverse transcription-polymerase chain reaction and slot
      blot analysis, and levels of protein were estimated by enhanced chemiluminescence
      light Western blot analysis. The levels of the NHE-1 mRNA and protein in colonic
      mucosa increased as assessed at 1, 2, 5 and 7 days post-acetic acid
      administration and 7 days post-trinitrobenzenesulphonic acid administration in
      the rats. The levels of mRNA were not suppressed by dexamethasone treatment in
      either case. These findings demonstrate that colitis-induced expression of the
      NHE-1 mRNA and protein is independent of the way colitis is induced. Although
      factor(s) responsible for the induction remain to be identified, our findings
      showing similar changes in the NHE-2 and NHE-3 mRNA isoforms, together with the
      lack of their suppression by dexamethasone, suggest that cytokines and
      intracellular pH are secondary factors.

PMID- 9580639
TI  - Dehydroepiandrosterone and analogs inhibit DNA binding of AP-1 and airway smooth
      muscle proliferation.
AB  - The adrenal steroid dehydroepiandrosterone (DHEA) and its analogs reduce growth
      of immortalized and malignant cell lines. We therefore explored their effects on
      the growth of airway smooth muscle, whose hyperplasia may lead to fixed airways
      obstruction and enhanced airways hyperresponsiveness in severe chronic asthma.
      DHEA and its potent analog 16 alpha-bromoepiandrosterone dramatically reduced
      proliferation in primary cultures of rat tracheal smooth muscle stimulated with
      fetal bovine serum or platelet-derived growth factor. Growth inhibition was dose
      dependent and could not be attributed to interference with glucose-6-phosphate
      dehydrogenase activity or cholesterol metabolism, as reported for immortalized or
      malignant cell lines, respectively. Expression of the early response gene c-fos
      remained intact, but DHEA and 16 alpha-bromoepiandrosterone decreased DNA binding
      of the transcription factor activator protein-1, a later response important for
      expression of genes that mediate DNA synthesis and cell cycle progression. These
      results suggest that the nonglucocorticoid steroid DHEA and its analogs may
      impair activation of secondary growth response genes in a fashion analogous to
      that reported for glucocorticoids and that they may prove useful for treatment of
      asthmatic airway remodeling in the human.

PMID- 9580640
TI  - Role of wild-type p53 on the antineoplastic activity of temozolomide alone or
      combined with inhibitors of poly(ADP-ribose) polymerase.
AB  - The DNA repair enzyme O6-alkylguanine DNA-alkyltransferase (OGAT) and a deficient
      mismatch repair system play a critical role in the resistance to chemotherapeutic
      agents that generate adducts at the O6-position of guanine. However, DNA adducts
      different from O6-methylguanine might be also involved in cytotoxicity induced by
      methylating agents. Because the loss of p53 function is generally associated with
      tumor cell resistance to anticancer chemotherapy, we have investigated whether
      wild-type p53 might affect chemosensitivity of leukemia cells endowed with high
      OGAT levels to the methylating agent temozolomide (TZM). The effect of poly(ADP
      ribose) polymerase (PADPRP) inhibition, which potentiates the cytotoxic effects
      of N7-methylguanine and N3-methylguanine, was also assessed in OGAT-proficient
      cells, either susceptible or tolerant to O6-methylguanine. OGAT-proficient and
      p53 null HL60 cells were transfected with the human p53 cDNA (p53+ cells).
      Treatment with TZM concentrations not toxic for the cells transduced with the
      control vector (p53-cells), induced apoptosis in p53+ cells. These cells were
      characterized by a lower level of bcl-2 protein than p53- cells, whereas bax and
      OGAT expression was comparable in both lines. Inhibition of PADPRP potentiated
      the cytotoxic and apoptotic effects of TZM in either p53- or p53+ HL60 cells.
      Furthermore, PADPRP inhibitors potentiated apoptosis induced by TZM in Jurkat
      cells, which possess a mutated p53 gene and are tolerant to O6-methylguanine
      adducts. The analysis of cell cycle indicated that the drug combination of TZM
      and PADPRP inhibitors provoked G1 arrest only in p53+ cells. Conversely, G1
      arrest was not observed in p53+ cells exposed to TZM alone. It is possible to
      speculate that PADPRP inhibitors might affect the repair of DNA adducts that are
      processed differently from O6 methylguanine and induce a different pattern of
      cell cycle distribution. In conclusion, the results show that p53 increases
      apoptosis by TZM in OGAT-proficient cells and suggest the potential role of
      PADPRP inhibitors in enhancing TZM activity against leukemias independently of
      DNA repair systems.

PMID- 9580641
TI  - Pharmacological and immunocytochemical characterization of subtypes of alpha-1
      adrenoceptors in dog aorta.
AB  - In this study, the effects of nine alpha-1 adrenoceptor antagonists [prazosin, WB
      4101 (WB), chloroethylclonidine (CEC), 5-methylurapidil (5-MU), BMY 7378 (BMY),
      MDL 73005EF (MDL73), MDL 72832 (MDL72), RS 17053 (RS) and SK&F 105854 (SKF)] were
      studied on contractile responses to phenylephrine (PE) of the endothelium-denuded
      dog aorta in vitro. All antagonists, except CEC, 5-MU and RS, produced
      concentration-dependent competitive inhibition of contractile responses of the
      aorta to PE. The rightward shift of the concentration-response curves of PE
      yielded constant pKB values with increasing antagonist concentrations in most
      cases allowing a single pooled value to be determined: for prazosin, a pKB of
      8.99 +/- 0.11 (n = 20, KB of 1.03 nM); for WB, a pKB of 8.75 +/- 0.08 (n = 23, KB
      of 1.76 nM); for BMY, a pKB of 7.21 +/- 0.13 (n = 13, KB of 62 nM); for MDL72, a
      pKB of 7.95 +/- 0.15 (n = 12, KB of 11.2 nM); and for SK&F 105854, a pKB of 5.82
      +/- 0.08 (n = 15, KB of 1.52 microM). For MDL73, pKB values decreased with
      antagonist concentration: 7.88 +/- 0.06 at 10 nM, 7.56 +/- 0.28 at 100 nM and
      6.92 +/- 0.18 at 1000 nM, which suggests the presence of more than one receptor
      subtype. CEC (10 and 100 microM) almost completely inhibited responses to PE;
      lower concentrations had no significant effect. 5-MU (10-300 nM) and RS (3-300
      nM) were ineffective antagonists in this tissue. Because WB, a highly selective
      alpha-1D and alpha-1A adrenoceptor subtypes inhibitor, blocked PE responses (with
      less affinity than for alpha-1A adrenoceptors), and 5-MU and RS, which are
      selective blockers for alpha-1A adrenoceptor, were ineffective, we conclude that
      alpha-1A adrenoceptors are absent in the dog aorta. The effects of the less
      selective MDL72 were inconsistent with actions at alpha-1B or alpha-1D
      adrenoceptors. Although WB shifted the PE concentration-response curve to the
      right, the abilities of BMY, MDL73 and SKF to inhibit competitively PE
      contraction were of lower affinity compared with expectations for interaction
      with alpha-1D adrenoceptors; they are not the predominant subtype. The complete
      inhibition of PE responses by CEC suggests that the dog aorta contains the alpha
      1B adrenoceptor subtype. In immunocytochemical studies of the expression of alpha
      1B adrenoceptor, all cells apparently expressed this protein. Moreover, Western
      blot studies of the microsomal fractions confirmed the presence of alpha-1B
      adrenoceptors. In the dog aorta, the alpha-1 adrenoceptors predominantly resemble
      alpha-1B rather than alpha-1D adrenoceptors as reported in the rat aorta.

PMID- 9580642
TI  - Nociceptin-induced inhibition of tachykinergic neurotransmission in guinea pig
      bronchus.
AB  - Nociceptin is a novel neuropeptide of the opioid peptide family recently
      identified as the endogenous ligand of the opioid receptor-like "orphan"
      receptor. Unlike other opioids, nociceptin has hyperalgesic effects in vivo. In
      the present study, nociceptin was found to inhibit electrical field stimulation
      induced tachykinergic contractions of the guinea pig isolated bronchus
      preparation. The threshold effect was about 1 nM, and at 0.1 microM, nociceptin
      inhibited contractions evoked by 5-Hz stimulation by more than 50%. This
      inhibitory effect was found to be mediated by a prejunctional mechanism involving
      none of the classical (mu, delta and kappa) opioid receptors. Although the
      hypothesis that the effect of nociceptin was secondary to opioid receptor-like
      stimulation cannot be pharmacologically addressed, opioid receptor-like-receptor
      mRNA was found to be expressed in the upper vagal sensory ganglion, where the
      cell bodies of the tachykinin-containing sensory neurons are located. Nociceptin
      immunoreactive nerve fibers in the airway wall, distinct from the tachykinin
      containing fibers, were identified as an endogenous source of nociceptin. These
      data indicate that nociceptin may influence airway physiology by modulating
      tachykinergic neurotransmission.

PMID- 9580643
TI  - Intake of high-fat food is selectively enhanced by mu opioid receptor stimulation
      within the nucleus accumbens.
AB  - The present study was designed to further investigate the nature of feeding
      induced by opioid stimulation of the nucleus accumbens through an examination of
      the effects of intra-accumbens (ACB) opioids on macronutrient selection. In 3-hr
      tests of free-feeding (satiated) rats, intra-ACB administration of the mu
      receptor agonist D-Ala2,N,Me-Phe4, Gly-ol5-enkephalin (DAMGO; 0, 0.025, 0.25 and
      2.5 micrograms bilaterally) markedly enhanced the intake of fat or carbohydrate
      when the diets were presented individually (although the effect on fat intake was
      much greater in magnitude). Intra-ACB injections of DAMGO, however, produced
      potent preferential stimulatory effects on fat ingestion with no effect on
      carbohydrate ingestion when both fat and carbohydrate diets were present
      simultaneously. Moreover, this selective stimulation of fat intake was
      independent of base-line diet preference and could be blocked by systemic
      injection of naltrexone (5 mg/kg). We also examined the effect of 24-hr food
      deprivation on the pattern of macronutrient intake in rats with access to both
      carbohydrate and fat. In contrast to the DAMGO-induced selective enhancement of
      fat intake, food deprivation significantly increased the intake of both diets to
      the same extent; however, in this case, only the stimulated fat intake was
      blocked by systemic naltrexone. Intra-ACB administration of DAMGO in hungry rats
      produced an effect similar to that observed in free-feeding rats; preference was
      strongly shifted to fat intake. Similarly, the opioid antagonist naltrexone (20
      micrograms) infused directly into ACB preferentially decreased fat intake in
      hungry rats. These findings suggest that endogenous opioids within the ventral
      striatum may participate in the mechanisms governing preferences for highly
      palatable foods, especially those rich in fat.

PMID- 9580644
TI  - IL-10 synergizes with dexamethasone in inhibiting human T cell proliferation.
AB  - We have evaluated the effects of dexamethasone (Dex) alone or in combination with
      interleukin (IL)-10 or transforming growth factor-beta 1 (TGF-beta 1) on human T
      cell proliferation. Both IL-10 and TGF-beta 1 significantly decreased the Dex
      concentration needed to inhibit T cell proliferation by 50% (IC50). Dex in
      combination with IL-10 completely inhibited T cell proliferation, even when IL-10
      alone was ineffective, as in the case of phytohemagglutinin-induced T cell
      proliferation. The evaluation of the results according to the isobole method
      displayed a potent synergistic activity between Dex and IL-10, whereas the
      combination of Dex with TGF-beta 1 was additive. IL-10, but not TGF-beta 1,
      enhanced the inhibitory effect of Dex on IL-2 production. IL-2 and IL-4 only
      partly antagonized the antiproliferative effect of the combinations. IL-4 was as
      effective as IL-2 in antagonizing the combination of Dex with TGF-beta 1, but
      significantly less effective against the combination of Dex with IL-10. IL-10 and
      TGF-beta 1 are thus able to potentiate the Dex inhibitory effect on T cell
      proliferation and could be regarded as potential agents for future
      immunosuppressive protocols.

PMID- 9580645
TI  - Spontaneous and cationic lipid-mediated uptake of antisense oligonucleotides in
      human monocytes and lymphocytes.
AB  - Monocytes are important target cells for anti-inflammatory antisense strategies.
      However, monocytes are characterized by strong phagocytic and catalytic activity
      which may limit the effect of antisense oligonucleotides. Intracellular
      distribution of oligonucleotides in monocytes and the effect of cationic lipids
      on oligonucleotide uptake in monocytes and other leukocytes have not been
      evaluated. We investigated cationic lipid-mediated uptake of oligonucleotides in
      human monocytes and lymphocyte subpopulations. Incorporation of oligonucleotides
      was quantified by flow cytometry and by confocal microscopy. In the absence of
      cationic lipids, nearly 100% of monocytes and of B lymphocytes incorporated
      oligonucleotides compared with only 12% of natural killer cells and 1% of T
      lymphocytes. The amount of oligonucleotide uptake per cell, as determined by mean
      fluoresence intensity of positive cells, was four times higher in monocytes than
      in B lymphocytes. Cationic lipids, which form complexes with oligonucleotides,
      markedly enhanced the amount of oligonucleotide uptake in all cell types and were
      most effective at a ratio of 1.1 of positive-to-negative molar charges. In
      monocytes, oligonucleotides incorporated spontaneously (without a lipid carrier)
      were trapped in cytoplasmic vesicles. In contrast, cationic lipid-mediated uptake
      of fluorescence-labeled oligonucleotides resulted in cytoplasmic and nuclear
      staining. We conclude that 1) monocyte and lymphocyte subpopulations differ in
      the degree of spontaneous oligonucleotide uptake, and 2) lipofectin both
      quantitatively and qualitatively affects this uptake. Our results may explain the
      necessary role of cationic lipids in most antisense models with leukocytes as
      target cells.

PMID- 9580646
TI  - Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group.
AB  - BACKGROUND: Sildenafil is a potent inhibitor of cyclic guanosine monophosphate
      hydrolysis [corrected] in the corpus cavernosum and therefore increases the
      penile response to sexual stimulation. We evaluated the efficacy and safety of
      sildenafil, administered as needed in two sequential double-blind studies of men
      with erectile dysfunction of organic, psychogenic, and mixed causes. METHODS: In
      a 24-week dose-response study, 532 men were treated with oral sildenafil (25, 50,
      or 100 mg) or placebo. In a 12-week, flexible dose-escalation study, 329
      different men were treated with sildenafil or placebo, with dose escalation to
      100 mg based on efficacy and tolerance. After this dose-escalation study, 225 of
      the 329 men entered a 32-week, open-label extension study. We assessed efficacy
      according to the International Index of Erectile Function, a patient log, and a
      global-efficacy question. RESULTS: In the dose-response study, increasing doses
      of sildenafil were associated with improved erectile function (P values for
      increases in scores for questions about achieving and maintaining erections were
      <0.001). For the men receiving 100 mg of sildenafil, the mean score for the
      question about achieving erections was 100 percent higher after treatment than at
      base line (4.0 vs. 2.0 of a possible score of 5). In the last four weeks of
      treatment in the dose-escalation study, 69 percent of all attempts at sexual
      intercourse were successful for the men receiving sildenafil, as compared with 22
      percent for those receiving placebo (P<0.001). The mean numbers of successful
      attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those
      receiving placebo (P<0.001). Headache, flushing, and dyspepsia were the most
      common adverse effects in the dose-escalation study, occurring in 6 percent to 18
      percent of the men. Ninety-two percent of the men completed the 32-week extension
      study. CONCLUSIONS: Oral sildenafil is an effective, well-tolerated treatment for
      men with erectile dysfunction.

PMID- 9580647
TI  - The efficacy of live attenuated, cold-adapted, trivalent, intranasal
      influenzavirus vaccine in children.
AB  - BACKGROUND: Influenzavirus vaccine is used infrequently in healthy children, even
      though the rates of influenza in this group are high. We conducted a multicenter,
      double-blind, placebo-controlled trial of a live attenuated, cold-adapted,
      trivalent influenzavirus vaccine in children 15 to 71 months old. METHODS: Two
      hundred eighty-eight children were assigned to receive one dose of vaccine or
      placebo given by intranasal spray, and 1314 were assigned to receive two doses
      approximately 60 days apart. The strains included in the vaccine were
      antigenically equivalent to those in the inactivated influenzavirus vaccine in
      use at the time. The subjects were monitored with viral cultures for influenza
      during the subsequent influenza season. A case of influenza was defined as an
      illness associated with the isolation of wild-type influenzavirus from
      respiratory secretions. RESULTS: The intranasal vaccine was accepted and well
      tolerated. Among children who were initially seronegative, antibody titers
      increased by a factor of four in 61 to 96 percent, depending on the influenza
      strain. Culture-positive influenza was significantly less common in the vaccine
      group (14 cases among 1070 subjects) than the placebo group (95 cases among 532
      subjects). The vaccine efficacy was 93 percent (95 percent confidence interval,
      88 to 96 percent) against culture-confirmed influenza. Both the one-dose regimen
      (89 percent efficacy) and the two-dose regimen (94 percent efficacy) were
      efficacious, and the vaccine was efficacious against both strains of influenza
      circulating in 1996-1997, A(H3N2) and B. The vaccinated children had
      significantly fewer febrile illnesses, including 30 percent fewer episodes of
      febrile otitis media (95 percent confidence interval, 18 to 45 percent; P<0.001).
      CONCLUSIONS: A live attenuated, cold-adapted influenzavirus vaccine was safe,
      immunogenic, and effective against influenza A(H3N2) and B in healthy children.

PMID- 9580648
TI  - Epstein-Barr virus and a cellular signaling pathway in lymphomas from
      immunosuppressed patients.
AB  - BACKGROUND: Epstein-Barr virus (EBV) is associated with various malignant and
      benign lymphoproliferative disorders. It also efficiently transforms human B
      lymphocytes in vitro. The latent membrane protein 1 (LMP1) of EBV-infected cells
      plays a central part in this process by mimicking members of the family of tumor
      necrosis factor (TNF) receptors, thereby transmitting growth signals from the
      cell membrane to the nucleus through cytoplasmic TNF-receptor-associated factors
      (TRAFs). I sought evidence of LMP1-mediated signal transduction through TRAFs in
      tumor tissue from patients with post-transplantation lymphoproliferative disease
      and non-Hodgkin's lymphomas related to the acquired immunodeficiency syndrome
      (AIDS). METHODS: The association of LMP1 with TRAF-1 or TRAF-3 in tumor tissue
      was studied with double-immunofluorescence microscopy and immunoprecipitation
      assays. Evidence of LMP1-TRAF signaling was sought with an electrophoretic
      mobility shift assay for the nuclear factor-kappaB (NF-kappaB) transcription
      factor. RESULTS: Tumors from eight patients with post-transplantation
      lymphoproliferative disease, two patients with AIDS-associated non-Hodgkin's
      lymphoma, and three patients with endemic Burkitt's lymphoma were analyzed.
      Tumors from six of the patients with post-transplantation lymphoproliferative
      disease were positive for EBV and expressed LMP1; two samples were EBV-negative.
      Tumors from both patients with AIDS-associated non-Hodgkin's lymphoma were EBV
      positive and expressed LMP1, whereas tumors from all three patients with
      Burkitt's tumors were positive for EBV but negative for LMP1. Double
      immunofluorescence microscopy showed that LMP1 localized with and
      immunoprecipitated with TRAF-1 and TRAF-3 in all eight of the EBV-positive, LMP1
      positive samples. An electrophoretic mobility shift assay revealed activated NF
      kappaB in all eight EBV-positive, LMP1-positive samples as well, but not in
      either of the EBV-negative, LMP1-negative samples or in the three EBV-positive,
      LMP1-negative samples. CONCLUSIONS: LMP1-mediated signaling through the TRAF
      system has a role in the pathogenesis of the EBV-positive lymphomas that arise in
      immunosuppressed patients.

PMID- 9580649
TI  - Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation.

PMID- 9580650
TI  - Images in clinical medicine. Calcified mass in a patient on long-term
      hemodialysis.

PMID- 9580651
TI  - Dialysis therapy.

PMID- 9580652
TI  - Treatment of benign nodular thyroid disease.

PMID- 9580654
TI  - A pill for impotence.

PMID- 9580655
TI  - Influenza immunization for children.

PMID- 9580656
TI  - Epstein-Barr virus in action in vivo.

PMID- 9580657
TI  - Hepatocyte transplantation.

PMID- 9580658
TI  - The variable expressivity and incomplete penetrance of the twist-null
      heterozygous mouse phenotype resemble those of human Saethre-Chotzen syndrome.
AB  - Most targeted gene mutations are recessive and analyses of gene function often
      focus on homozygous mutant phenotypes. Here we describe parts of the expression
      pattern of M-twist in the head of developing wild-type mice and present our
      analysis of the phenotype of heterozygous twist- null animals at around birth and
      in adults. A number of twist -null heterozygous mice present skull and limb
      defects and, in addition, we observed other malformations, such as defects in
      middle ear formation and the xyphoid process. Our study is of interest to
      understand bone formation and the role of M-twist during this process, as within
      the same animal growth of some bones can be accelerated while for others it can
      be delayed. Moreover, we show here that expressivity of the mouse mutant
      heterozygous phenotype is dependent on the genetic background. This information
      might also be helpful for clinicians, since molecular defects affecting one
      allele of the human H-twist ( TWIST ) gene were identified in patients affected
      with Saethre-Chotzen syndrome (SCS). Expressivity of this syndrome is variable,
      although most patients present craniofacial and limb malformations resembling
      those seen in mutant mice. Thus the mutant mouse twist -null strain might be a
      useful animal model for SCS. The twist -null mutant mouse model, combined with
      other mutant mouse strains, might also help in an understanding of the etiology
      of morphological abnormalities that appear in human patients affected by other
      syndromes.

PMID- 9580660
TI  - Characterization of molecular defects in xeroderma pigmentosum group F in
      relation to its clinically mild symptoms.
AB  - Xeroderma pigmentosum (XP) complementation group F was first reported in Japan
      and most XP-F patients reported to date are Japanese. The clinical features of XP
      F patients are rather mild, including late onset of skin cancer. Recently a cDNA
      that corrects the repair deficiency of cultured XP-F cells was isolated. The XPF
      protein forms a tight complex with ERCC1 and this complex functions as a
      structure-specific endonuclease responsible for the 5' incision during DNA
      excision repair. Here we have identified XPF mRNA mutations and examined levels
      of the mRNA and protein expression in seven primary cell strains from Japanese XP
      F patients. The XP-F cell strains were classified into three types in terms of
      the effect of the mutation on the predicted protein; (i) XPF proteins with amino
      acid substitutions; (ii) amino acid substituted and truncated XPF proteins; and
      (iii) truncated XPF protein only. A normal level of expression of XPF mRNA was
      observed in XP-F cells but XPF protein was extremely low. These results indicate
      that the detected mutations lead to unstable XPF protein, resulting in a decrease
      in formation of the ERCC1-XPF endonuclease complex. Slow excision repair of UV
      induced DNA damage due to low residual endonuclease activity provides a plausible
      explanation for the typical mild phenotype of XP-F patients.

PMID- 9580659
TI  - Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide
      repeat instability.
AB  - X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat
      expansion in the first exon of the androgen receptor (AR) gene. Disease
      associated alleles (37-66 CAGs) change in length when transmitted from parents to
      offspring, with a significantly greater tendency to shift size when inherited
      paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats
      do not display repeat instability, we attempted to model trinucleotide repeat
      instability by generating transgenic mice with yeast artificial chromosomes
      (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of
      independent lines of AR YAC transgenic mice with CAG 45 alleles reveal
      intergenerational instability at an overall rate of approximately 10%. We also
      find that the 45 CAG repeat tracts are significantly more unstable with maternal
      transmission and as the transmitting mother ages. Of all the CAG/CTG repeat
      transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the
      smallest trinucleotide repeat mutations, suggesting that the length threshold for
      repeat instability in the mouse may be lowered by including the appropriate
      flanking human DNA sequences. By sequence-tagged site content analysis and long
      range mapping we determined that one unstable transgenic line has integrated an
      approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC.
      Identification of the cis -acting elements that permit CAG tract instability and
      the trans -acting factors that modulate repeat instability in the AR YAC CAG 45
      mice may provide insights into the molecular basis of trinucleotide repeat
      instability in humans.

PMID- 9580661
TI  - Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome
      and implications for treatment.
AB  - The antenatal variant of Bartter's syndrome is an autosomal recessive kidney
      disease characterized by polyhydramnios, premature delivery, hypokalemic
      alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked
      recently to mutations in an ATP-sensitive, renal outer medullary K+channel, ROMK,
      and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized
      four of the mutations reported in three heterozygous ROMK variants of antenatal
      Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One
      mutation expressed normal function and appears to be an allelic polymorphism. The
      other three mutations produced channels with significantly reduced K+fluxes.
      However, the mechanisms in each case were different and reflected abnormalities
      in phosphorylation, proteolytic processing or protein trafficking. The different
      mechanisms may be important in the design of appropriate therapy for patients
      with this disease.

PMID- 9580662
TI  - Reduced collagen VI causes Bethlem myopathy: a heterozygous COL6A1 nonsense
      mutation results in mRNA decay and functional haploinsufficiency.
AB  - We have identified a new pathogenic mechanism for an inherited muscular dystrophy
      in which functional haploinsufficiency of the extracellular matrix protein
      collagen VI causes Bethlem myopathy. The heterozygous COL6A1 mutation results in
      a single base deletion from the mRNA and a premature stop codon. The mutant mRNA
      is unstable, subject to nonsense-mediated mRNA decay, and is almost completely
      absent both from patient fibroblasts and skeletal muscle, resulting in
      haploinsufficiency of the alpha1(VI) subunit and reduced production of
      structurally normal collagen VI. This is the first example of a muscular
      dystrophy caused by haploinsufficiency of a structural protein or member of the
      dystrophin-glycoprotein complex, and identifies collagen VI as a critical
      contributor to cell-matrix adhesion in skeletal muscle.

PMID- 9580663
TI  - Ataxin-3 is transported into the nucleus and associates with the nuclear matrix.
AB  - It has been reported that the ataxin-3 protein containing a polyglutamine
      sequence in the pathological range (61-84Q) is localized within the nucleus of
      neuronal cells, whereas ataxin-3 with a normal repeat length (12-37Q) is
      predominantly a cytoplasmic protein. In this study, the subcellular localization
      of the full-length ataxin-3 protein with a glutamine sequence in the normal range
      (Q3KQ22) was analysed in two mammalian cell lines. Using two affinity-purified
      polyclonal antibodies raised against the N- or C-terminal portion of ataxin-3,
      the protein was detected predominantly, but not exclusively, in the nucleus of
      COS-7 as well as neuroblastoma cells by immunofluorescence and confocal laser
      scanning microscopy (CLSM). The distribution of the protein in these cellular
      compartments was confirmed by biochemical subcellular fractionations.
      Furthermore, CLSM revealed that the ataxin-3 protein present in the nucleus of
      neuroblastoma cells is associated with the inner nuclear matrix. Our results
      taken together with the finding of a nuclear localization signal in ataxin-3
      indicate that the ataxin-3 protein per se translocates to the nucleus and that an
      expanded glutamine repeat is not essential for this transport.

PMID- 9580664
TI  - L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired
      exploration patterns.
AB  - L1 is a neural cell adhesion molecule mainly involved in axon guidance and
      neuronal migration during brain development. Mutations in the human L1 gene give
      rise to a complex clinical picture, with mental retardation, neurologic
      abnormalities and a variable degree of hydrocephalus. Recently, a transgenic
      mouse model with a targeted null mutation in the L1 gene was generated. These
      knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have
      performed further studies of these KO mice including magnetic resonance imaging
      of the brain, neuropathological analysis and behavioral testing. The ventricular
      system was shown to be abnormal with dilatation of the lateral ventricles and the
      4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the
      cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is
      characterized by stereotype peripheral circling reminiscent of that of rodents
      with induced cerebellar lesions.

PMID- 9580665
TI  - Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal
      age effect on level of recombination.
AB  - Non-disjoined chromosomes 15 from 115 cases of uniparental disomy (ascertained
      through Prader-Willi syndrome) and 13 cases of trisomy of maternal origin were
      densely typed for microsatellite loci spanning chromosome 15q. Of these 128 cases
      a total of 97 meiosis I (MI) errors, 19 meiosis II (MII) errors and 12 mitotic
      errors were identified. The genetic length of a map created from the MI errors
      was 101 cM, as compared with a maternal length of 137 cM based on CEPH controls.
      No significant differences were detected in the distribution of recombination
      events along the chromosome arm and a reduction was seen for most of the
      chromosome 15 intervals examined. It was estimated that 21% of tetrads leading to
      MI non-disjunction were achiasmate, which may account for most or all of the
      reduction in recombination noted. The mean age of mothers of cases involving MI
      errors which showed no transitions from heterodisomy to isodisomy was
      significantly lower (32.7) than cases showing one or more observable transitions
      (36.3) (P < 0.003, t -test). However, even among chiasmate pairs the highest mean
      maternal age was seen for multiple exchange tetrads. Chromosome-specific
      differences in maternal age effects may be related to the normal distribution of
      exchanges (and their individual susceptibilities) for each chromosome. However,
      they may also reflect the presence of multiple factors which act to ensure normal
      segregation, each affected by maternal age in a different way and varying in
      importance for each chromosome.

PMID- 9580666
TI  - An elastin gene mutation producing abnormal tropoelastin and abnormal elastic
      fibres in a patient with autosomal dominant cutis laxa.
AB  - Elastin is the protein responsible for the characteristic elastic properties of
      many tissues including the skin, lungs and large blood vessels. Loss-of-function
      mutations in the elastin gene are known to cause the heart defect supravalvular
      aortic stenosis (SVAS). We and others have identified deletions, nonsense
      mutations and splice site mutations in SVAS patients that abolish the function of
      one elastin gene. We have now identified an elastin mutation in a patient with a
      completely different phenotype, the rare autosomal dominant condition cutis laxa.
      A frameshift mutation in exon 32 of the elastin gene is predicted to replace 37
      amino acids at the C-terminus of elastin by a novel sequence of 62 amino acids.
      mRNA and immunoprecipitation studies show that the mutant allele is expressed.
      Electron microscopy of skin sections shows abnormal branching and fragmentation
      in the amorphous elastin component, and immunocytochemistry shows reduced elastin
      deposition in the elastic fibres and fewer microfibrils in the dermis. These
      findings suggest that the mutant tropoelastin protein is synthesized, secreted
      and incorporated into the elastic matrix, where it alters the architecture of
      elastic fibres. Interference with cross-linking would reduce elastic recoil in
      affected tissues and explain the cutis laxa phenotype.

PMID- 9580667
TI  - Mutation detection by a two-hybrid assay.
AB  - Yeast-based assays have been developed to detect inactivating mutations in human
      genes, but these assays generally rely on the human protein having a biological
      function in yeast. We describe a simple method to detect mutations by virtue of
      their ability to abolish a protein-protein interaction in the yeast two-hybrid
      assay. By the use of direct recombinational cloning in yeast of a reverse
      transcription-PCR product followed by a simple growth selection this method
      distinguished both homozygous and heterozygous mutations in the p53 tumor
      suppressor gene. This approach should be applicable to many human genes whose
      encoded proteins have suitable partners in the two-hybrid assay.

PMID- 9580668
TI  - A new spontaneous mouse mutation of Hoxd13 with a polyalanine expansion and
      phenotype similar to human synpolydactyly.
AB  - Human synpolydactyly (SPD) is an inherited congenital limb malformation caused by
      mutations in the HOXD13 gene. Heterozygotes are typically characterized by 3/4
      finger and 4/5 toe syndactyly with associated duplicated digits; hands and feet
      of homozygotes are very small because of a shortening of the phalanges,
      metacarpal and metatarsal bones. Here we describe the phenotype and molecular
      basis of a spontaneous mutation of Hoxd13 in mice that provides a phenotypically
      and molecularly accurate model for human SPD. The new mutation, named
      synpolydactyly homolog (spdh), is a 21 bp in-frame duplication within a
      polyalanine-encoding region at the 5'-end of the Hoxd13 coding sequence. The
      duplication expands the stretch of alanines from 15 to 22; the same type of
      expansion occurs in human SPD mutations. spdh/spdh homozygotes exhibit severe
      malformations of all four feet, including polydactyly, syndactyly and
      brachydactylia. The phenotype of spdh is much more severe than that exhibited by
      mice with a genetically engineered, presumably null, disruption of Hoxd13. Thus
      spdh probably acts in a dominant-negative manner and will be valuable for
      examining interactions with other Hox genes and their protein products during
      limb development. Homozygous mice of both sexes also lack preputial glands and
      males do not breed; therefore, spdh/spdh mice may also be valuable in studies of
      reproductive physiology and behavior.

PMID- 9580669
TI  - CSR, a scavenger receptor-like protein with a protective role against cellular
      damage causedby UV irradiation and oxidative stress.
AB  - Oxidative stress is a pathogenic condition that causes cellular damage and, in a
      normally functioning cell, several transcription factors respond to this threat
      by modulating expression of genes whose products ameliorate the altered redox
      status in some way. We have isolated a novel macrophage scavenger receptor-like
      gene, CSR (cellular stress response), whose transcription in normal fibroblasts
      was significantly elevated by exposure to UV radiation or hydrogen peroxide, and
      pre-treatment with antioxidants prevented induction of CSR . Under conditions of
      oxidative stress, reactive oxygen species were significantly depleted in CSR 
      overexpressing cells, indicating that the CSR product protects cells by
      scavenging oxidative molecules or harmful products of oxidation. Further
      investigations into the regulation and function of CSR should open a way to
      understanding the cellular response and the pathogenic processes caused by
      oxidative stress.

PMID- 9580670
TI  - A dinucleotide mutation in the endothelin-B receptor gene is associated with
      lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease.
AB  - Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized
      by a white coat colour and aganglionosis of the bowel, which is similar to
      Hirschsprung disease (HSCR). We decided to investigate possible mutations of the
      endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents
      and some patients have demonstrated EDNRB defects. First, we identified a full
      length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading
      frame which encoded 443 amino acid residues. The predicted amino acid sequence
      was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB
      respectively, but only 55% identical to the human, bovine and rat endothelin A
      receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR
      and the amplification-created restriction site (ACRS) technique, revealed a
      dinucleotide TC-->AG mutation, which changed isoleucine to lysine in the
      predicted first transmembrane domain of the EDNRB protein. This was associated
      with LWFS when homozygous and with the overo phenotype when heterozygous.

PMID- 9580671
TI  - Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products.
AB  - Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by a mutation
      in either the TSC1 or TSC2 tumour suppressor gene. The disease is characterized
      by a broad phenotypic spectrum that can include seizures, mental retardation,
      renal dysfunction and dermatological abnormalities. TSC2 encodes tuberin, a
      putative GTPase activating protein for rap1 and rab5. The TSC1 gene was recently
      identified and codes for hamartin, a novel protein with no significant homology
      to tuberin or any other known vertebrate protein. Here, we show that hamartin and
      tuberin associate physically in vivo and that the interaction is mediated by
      predicted coiled-coil domains. Our data suggest that hamartin and tuberin
      function in the same complex rather than in separate pathways.

PMID- 9580673
TI  - Characterization of protein-binding to the spinach chloroplast psbA mRNA 5'
      untranslated region.
AB  - RNA-binding proteins play a major role in regulating mRNA metabolism in
      chloroplasts. In this work we characterized two proteins, of 43 and 47 kDa, which
      bind to the spinach psbA mRNA 5' untranslated region (psbA encoding the D1
      protein of photosystem II). The 43 kDa protein, which is present in the stroma
      and in membranes, co-sediments with a complex of 68S. It was purified, and the N
      terminal sequence was determined. Upon homology search it was identified as the
      chloroplast homologue of the Escherichia coli ribosomal protein S1. The 47 kDa
      protein, which, in contrast with the 43 kDa protein, sediments with a small
      sedimentation coefficient, is only detected in the stromal fraction. It is
      soluble in an uncomplexed form. By deletion analysis, an element within the psbA
      mRNA 5' untranslated region was identified that is necessary but not sufficient
      for binding of stromal proteins. The 'central protein binding element' ranges
      from nucleotide -49 to -9 of the psbA mRNA 5' untranslated region. It comprises
      the Shine-Dalgarno-like GGAG motif and, 7 nucleotides upstream, an
      endonucleolytic cleavage site involved in psbA mRNA degradation in vitro . The
      mechanistic impacts of this region in relation to RNA-binding proteins are
      discussed.

PMID- 9580675
TI  - Extending the cleavage rules for the hammerhead ribozyme: mutating adenosine15.1
      to inosine15.1 changes the cleavage site specificity from N16.2U16.1H17 to
      N16.2C16.1H17.
AB  - In this paper, we show that an adenosine to inosine mutation at position 15.1
      changes the substrate specificity of the hammerhead ribozyme from N16.2U16.1H17to
      N16.2C16.1H17(H represents A, C or U). This result extends the hammerhead
      cleavage triplet definition from N16.2U16.1H17to the more general N16.2Y16.1H17.
      Comparison of cleavage rates using I15.1ribozymes for NCH triplets and standard
      A15.1 ribozymes for NUH triplets under single turnover conditions shows similar
      or slightly enhanced levels of reactivity for the I15. 1-containing structures.
      The effect of I15.1 substitution was also tested in nuclease-resistant 2'- O 
      alkyl substituted derivatives (oligozymes), showing a similar level of activity
      for the NUH and NCH cleaving structures. The availability of NCH triplets that
      can be targeted without loss of efficiency increases the flexibility of ribozyme
      targeting strategies. This was demonstrated by an efficient cleavage of an HCV
      transcript at a previously inaccessible GCA site in codon 2.

PMID- 9580672
TI  - Identifying 5-methylcytosine and related modifications in DNA genomes.
AB  - Intense interest in the biological roles of DNA methylation, particularly in
      eukaryotes, has produced at least eight different methods for identifying 5
      methylcytosine and related modifications in DNA genomes. However, the utility of
      each method depends not only on its simplicity but on its specificity,
      resolution, sensitivity and potential artifacts. Since these parameters affect
      the interpretation of data, they should be considered in any application.
      Therefore, we have outlined the principles and applications of each method,
      quantitatively evaluated their specificity,resolution and sensitivity, identified
      potential artifacts and suggested solutions, and discussed a paradox in the
      distribution of m5C in mammalian genomes that illustrates how methodological
      limitations can affect interpretation of data. Hopefully, the information and
      analysis provided here will guide new investigators entering this exciting field.

PMID- 9580674
TI  - Selective inhibition of cell-free translation by oligonucleotides targeted to a
      mRNA hairpin structure.
AB  - Using an in vitro selection approach we have previously isolated oligodeoxy
      aptamers that can bind to a DNA hairpin structure without disrupting the double
      stranded stem. We report here that these oligomers can bind to the RNA version of
      this hairpin, mostly through pairing with a designed 6 nt anchor. The part of the
      aptamer selected against the DNA hairpin did not increase stability of the RNA
      aptamer complex. However, it contributed to the binding site for Escherichia coli
      RNase H, leading to very efficient cleavage of the target RNA. In addition, a 2'-
      O -methyloligoribonucleotide analogue of one selected sequence selectively
      blocked in vitro translation of luciferase in wheat germ extract by binding to
      the hairpin region inserted upstream of the initiation codon of the reporter
      gene. Therefore, non-complementary oligomers can exhibit antisense properties
      following hybridization with the target RNA. Our study also suggests that in
      vitro selection might provide a means to extend the repertoire of sequences that
      can be targetted by antisense oligonucleotides to structured RNA motifs of
      biological importance.

PMID- 9580676
TI  - Analyzing genomes with cumulative skew diagrams.
AB  - A novel method of cumulative diagrams shows that the nucleotide composition of a
      microbial chromosome changes at two points separated by about a half of its
      length. These points coincide with sites of replication origin and terminus for
      all bacteria where such sites are known. The leading strand is found to contain
      more guanine than cytosine residues. This fact is used to predict origin and
      terminus locations in other bacterial and archaeal genomes. Local changes,
      visible as diagram distortions, may represent recent genome rearrangements, as
      demonstrated for two strains of Escherichia coli . Analysis of the diagrams of
      viral and mitochondrial genomes suggests a link between the base composition bias
      and the time spent by DNA in a single stranded state during replication.

PMID- 9580677
TI  - A novel splice variant of the transcription factor Nrf1 interacts with the
      TNFalpha promoter and stimulates transcription.
AB  - Common signaling chains of various receptor families, despite some similarities,
      are able to provoke quite different cellular responses. This suggests that they
      are linked to different cascades and transcription factors, dependent on the
      context of the ligand binding moiety and the cell type. The ITAM (immunoreceptor
      tyrosine-based activation motif) containing gamma chain of the FcepsilonRI,
      FcgammaRI, FcgammaRIII and the T-cell receptor is one of these shared signaling
      molecules. Here, we show that in the context of the FcgammaRIII, the gamma chain
      activates the transcription factor Nrf1 or a closely related protein that
      specifically interacts with the extended kappa3 site in the TNFalpha promoter. A
      novel splice variant of Nrf1 with a 411 bp deletion of the serine-rich region,
      resulting in an overall structure reminiscent of the BTB and CNC homology (Bach)
      proteins, was isolated from the corresponding DC18 cells. In a gel shift
      analysis, this bacterially expressed splice variant binds to the TNFalpha
      promoter site after in vitro phosphorylation by casein kinase II (CKII). In
      addition, cotransfection studies demonstrate that this splice variant mediates
      induced transcription at the TNFalpha promoter after stimulation/activation in a
      heterologous system.

PMID- 9580679
TI  - Quantitative parameters for amino acid-base interaction: implications for
      prediction of protein-DNA binding sites.
AB  - Inspection of the amino acid-base interactions in protein-DNA complexes is
      essential to the understanding of specific recognition of DNA target sites by
      regulatory proteins. The accumulation of information on protein-DNA co-crystals
      challenges the derivation of quantitative parameters for amino acid-base
      interaction based on these data. Here we use the coordinates of 53 solved protein
      DNA complexes to extract all non-homologous pairs of amino acid-base that are in
      close contact, including hydrogen bonds and hydrophobic interactions. By
      comparing the frequency distribution of the different pairs to a theoretical
      distribution and calculating the log odds, a quantitative measure that expresses
      the likelihood of interaction for each pair of amino acid-base could be
      extracted. A score that reflects the compatibility between a protein and its DNA
      target can be calculated by summing up the individual measures of the pairs of
      amino acid-base involved in the complex, assuming additivity in their
      contributions to binding. This score enables ranking of different DNA binding
      sites given a protein binding site and vice versa and can be used in molecular
      design protocols. We demonstrate its validity by comparing the predictions using
      this score with experimental binding results of sequence variants of zif268 zinc
      fingers and their DNA binding sites.

PMID- 9580678
TI  - Effects of phosphate neutralization on the shape of the AP-1 transcription factor
      binding site in duplex DNA.
AB  - Previous electrophoretic experiments suggest that the AP-1 site in duplex DNA
      bends in response to the pattern of amino acid charges distal to the basic region
      in bound bZIP proteins. The extent and direction of apparent DNA bending are
      consistent with the prediction that DNA will collapse locally upon asymmetric
      phosphate charge neutralization. To prove that asymmetric phosphate
      neutralization could produce the observed degree of DNA bending, the present
      experiments partially substitute anionic phosphate diesters in the AP-1 site with
      various numbers of neutral methylphosphonate linkages. DNA bending is induced
      toward the neutralized face of DNA. The degree of DNA bending induced by
      methylphosphonate substitution (approximately 3.5 degrees per neutralized
      phosphate) is comparable to that induced by GCN4 variants carrying increasing
      numbers of additional basic amino acids. It is plausible, therefore, that
      asymmetric phosphate neutralization is the cause of DNA bending in such
      complexes.

PMID- 9580680
TI  - oriGNAI3: a narrow zone of preferential replication initiation in mammalian cells
      identified by 2D gel and competitive PCR replicon mapping techniques.
AB  - The nature of mammalian origins of DNA replication remains controversial and this
      is primarily because two-dimensional gel replicon mapping techniques have
      identified broad zones of replication initiation whereas several other
      techniques, such as quantitative PCR, have disclosed more discrete sites of
      initiation at the same chromosomal loci. In this report we analyze the
      replication of an amplified genomic region encompassing the 3'-end of the GNAI3
      gene, the entire GNAT2 gene and the intergenic region between them in
      exponentially growing Chinese hamster fibroblasts. These cells express GNAI3 but
      not GNAT2 . The replication pattern was first analyzed by two-dimensional neutral
      alkaline gel electrophoresis. Surprisingly, the results revealed a small
      preferential zone of replication initiation, of at most 1.7 kb, located in a
      limited part of the GNAI3 - GNAT2 intergenic region. Mapping of this initiation
      zone was then confirmed by quantitative PCR. The agreement between the two
      techniques exploited here strengthens the hypothesis that preferred sites of
      replication initiation do exist in mammalian genomes.

PMID- 9580681
TI  - In vitro DNA binding of the archaeal protein Sso7d induces negative supercoiling
      at temperatures typical for thermophilic growth.
AB  - The topological state of DNA in hyperthermophilic archaea appears to correspond
      to a linking excess in comparison with DNA in mesophilic organisms. Since DNA
      binding proteins often contribute to the control of DNA topology by affecting DNA
      geometry in the presence of DNA topoisomerases, we tested whether the histone
      like protein Sso7d from the hyperthermophilic archaeon Sulfolobus solfataricus
      alters DNA conformation. In ligase-mediated supercoiling assays carried out at
      37, 60, 70, 80 and 90 degrees C we found that DNA binding of increasing amounts
      of Sso7d led to a progressive decrease in plasmid linking number (Lk), producing
      negative supercoiling. Identical unwinding effects were observed when recombinant
      non-methylated Sso7d was used. For a given Sso7d concentration the DNA unwinding
      induced was augmented with increasing temperature. However, after correction for
      the overwinding effect of high temperature on DNA, plasmids ligated at 60-90
      degrees C exhibited similar sigma values at the highest Sso7d concentrations
      assayed. These results suggest that Sso7d may play a compensatory role in vivo by
      counteracting the overwinding effect of high temperature on DNA. Additionally,
      Sso7d unwinding could be involved in the topological changes observed during
      thermal stress (heat and cold shock), playing an analogous role in crenarchaeal
      cells to that proposed for HU in bacteria.

PMID- 9580682
TI  - Genomic footprinting of the yeast zinc finger protein Rme1p and its roles in
      repression of the meiotic activator IME1.
AB  - The zinc finger protein Rme1p is a negative regulator of the meiotic activator
      IME1 in Saccharomyces cerevisiae . Prior studies have shown that Rme1p binds in
      vitro to a site near nt -2030 in the IME1 upstream region, but a genomic mutation
      in that site has little effect on repression of IME1 . To identify Rme1p binding
      sites in vivo , we have examined the binding of Rme1p to genomic sites through in
      vivo footprinting. We show that Rme1p binds to two sites in the IME1 upstream
      region, near nt -1950 and -2030. Mutations in both binding sites abolish
      repression of chromosomal IME1 by Rme1p, whereas a mutation in either single site
      causes partial derepression. Therefore, both Rme1p binding sites are essential
      for repression of IME1 . Prior studies have shown that repression by Rme1p
      depends upon RGR1 and SIN4 , which specify RNA polymerase II mediator subunits
      that are required for normal nucleosome density. We find that RGR1 and SIN4 are
      not simply required for Rme1p to bind to DNA in vivo . These results suggest that
      Rme1p functions directly as a repressor of IME1 and that Rgr1p and Sin4p are
      required for DNA-bound Rme1p to exert repression.

PMID- 9580683
TI  - Structural requirements for DNA binding of GCM proteins.
AB  - Members of the GCM family of transcription factors contain a DNA binding domain
      unrelated to any other known DNA binding domain and bind to a DNA sequence motif
      not recognized by any other known transcription factor. Here we show that
      positions 2, 3, 6 and 7 of the 5'-ATGCGGGT-3' motif are particularly important
      for DNA binding and that methylation of several G residues on the upper strand,
      but not on the lower strand, interfered with binding of GCM proteins. No
      differences were detected between the DNA binding of Drosophila GCM and mammalian
      mGCMa. Alanine scan mutagenesis of the DNA binding domain of mGCMa identified the
      three conserved amino acids K74, C76 and C125 as being essential for DNA binding.
      Conserved cysteine residues were also found to be important for maintaining the
      overall integrity of the DNA binding domain and for mediating redox sensitivity
      of DNA binding. These cysteine residues are arranged in a symmetrical structure
      that bears no resemblance to other cysteine-containing structures, such as zinc
      fingers. In agreement with this, DNA binding of mGCMa was not dependent on zinc
      ions. Our results give insights into the exact nature of the GCM binding sites
      expected in target genes and point to a role for redox regulation in the function
      of GCM proteins.

PMID- 9580686
TI  - Cytarabine-induced destabilization of a model Okazaki fragment.
AB  - Cytarabine is a potent anticancer drug that interferes with elongation of the
      lagging strand at the replication fork during DNA synthesis. The effects of
      cytarabine substitution on the structural and thermodynamic properties of a model
      Okazaki fragment were investigated using UV hyperchromicity and 1H NMR
      spectroscopy to determine how cytarabine alters the physicochemical properties of
      Okazaki fragments that are intermediates during DNA replication. Two model
      Okazaki fragments were prepared corresponding to a primary initiation site for
      DNA replication in the SV40 viral genome. One model Okazaki fragment consisted of
      five ribo- and seven deoxyribonucleotides on the hybrid strand, together with its
      complementary (DNA) strand. The second model Okazaki fragment was identical to
      the first with the exception of cytarabine substitution for deoxycytidine at the
      third DNA nucleotide of the hybrid strand. Thermodynamic parameters for the
      duplex to single strand transition for each model Okazaki fragment were
      calculated from the concentration dependence of the T m at 260 nm. Cytarabine
      significantly decreased the stability of this model Okazaki fragment, decreasing
      the melting temperature from 46.8 to 42.4 degrees C at a concentration of 1.33 x
      10(-5) M. The free energy for the duplex to single strand transition was 1.2
      kcal/mol less favorable for the cytarabine-substituted Okazaki fragment relative
      to the control at 37 degrees C. Analysis of the temperature dependence of the
      imino1H resonances for the two duplexes demonstrated that cytarabine specifically
      destabilized the DNA:DNA duplex portion of the model Okazaki fragment. These
      results are consistent with inhibition of lagging strand DNA synthesis by
      cytarabine substitution resulting from destabilization of the DNA:DNA duplex
      portion of Okazaki fragments in vivo .

PMID- 9580684
TI  - A differential response of wild type and mutant promoters to TFIIIB70
      overexpression in vivo and in vitro.
AB  - TFIIIB, the initiation factor for transcription by RNA polymerase III (pol III)
      is, in yeast, composed of three subunits: TBP, TFIIIB70/Brf1 and TFIIIB90. To
      determine the extent to which each of these subunits is limiting for pol III
      transcription, the effect of overexpressing each subunit was assessed on the
      expression of wild-type and promoter mutant pol III genes both in vivo and in
      vitro . In vivo , we find that the synthesis of wild-type pol III genes is not
      limited to a significant extent by the level of any TFIIIB subunit. There is,
      however, a two-fold increase in the synthesis of the promoter mutant gene, sup9-e
      A19-supS1 , in strains overexpressing TFIIIB70. The findings suggest that
      overexpression of TFIIIB70has a differential effect on the expression of pol III
      genes with strong versus weak promoters. In vitro transcription assays support
      this conclusion and reveal an inverse correlation between the transcriptional
      response to TFIIIB70overexpression and promoter strength. The individual TFIIIB
      subunits are nuclear by immunofluorescence and are calculated to have nuclear
      concentrations in the low micromolar range. In comparison, the factors are
      diluted 100-fold or more in whole cell extracts. This dilution accounts for the
      generally limiting nature of TFIIIB70in pol III gene transcription in vitro.

PMID- 9580685
TI  - Cloned human FMR1 trinucleotide repeats exhibit a length- and orientation
      dependent instability suggestive of in vivo lagging strand secondary structure.
AB  - The normal human FMR1 gene contains a genetically stable (CGG) n trinucleotide
      repeat which usually carries interspersed AGG triplets. An increase in repeat
      number and the loss of interspersions results in array instability, predominantly
      expansion, leading to FMR1 gene silencing. Instability is directly related to the
      length of the uninterrupted (CGG) n repeat and is widely assumed to be related to
      an increased propensity to form G-rich secondary structures which lead to
      expansion through replication slippage. In order to investigate this we have
      cloned human FMR1 arrays with internal structures representing the normal,
      intermediate and unstable states. In one replicative orientation, arrays show a
      length-dependent instability, deletions occurring in a polar manner. With longer
      arrays these extend into the FMR1 5'-flanking DNA, terminating at either of two
      short CGG triplet arrays. The orientation-dependent instability suggests that
      secondary structure forms in the G-rich lagging strand template, resolution of
      which results in intra-array deletion. These data provide direct in vivo evidence
      for a G-rich lagging strand secondary structure which is believed to be involved
      in the process of triplet expansion in humans.

PMID- 9580687
TI  - Sequence specificity of illegitimate plasmid recombination in Bacillus subtilis:
      possible recognition sites for DNA topoisomerase I.
AB  - Previous work in our group indicated that structural plasmid instability in
      Bacillus subtilis is often caused by illegitimate recombination between non
      repeated sequences, characterized by a relatively high AT content. Recently we
      developed a positive selection vector for analysis of plasmid recombination
      events in B. subtilis which enables measurement of recombination frequencies
      without interference of selective growth differences of cells carrying wild-type
      or deleted plasmids. Here we have used this system to further analyse the
      sequence specificity of illegitimate plasmid recombination events and to assess
      the role of the host-encoded DNA topoisomerase I enzyme in this process. Several
      lines of evidence suggest that single-strand DNA nicks introduced by DNA
      topoisomerase I are a major source of plasmid deletions in pGP100. First, strains
      overproducing DNA topoisomerase I showed increased levels of plasmid deletion.
      Second, these deletions occurred predominantly (>90% of the recombinants) between
      non-repeated DNA sequences, the majority of which resemble potential DNA
      topoisomerase I target sites. Sequence alignment of 66 deletion end-points
      confirmed the previously reported high AT content and, most importantly, revealed
      a highly conserved C residue at position -4 relative to the site of cleavage at
      both deletion termini. Based on these genetic data we propose the following
      putative consensus cleavage site for DNA topoisomerase I of B.subtilis: 5'
      A/TCATA/TTAA/TA/TA-3'.

PMID- 9580689
TI  - Step-wise DNA relaxation and decatenation by NaeI-43K.
AB  - Nae I protein was originally isolated for its restriction endonuclease
      properties. Nae I was later discovered to either relax or cleave supercoiled DNA,
      depending upon whether Nae I position 43 contains a lysine (43K) or leucine (43L)
      respectively. Nae I-43K DNA relaxation activity appears to be the product of
      coupling separate endonuclease and ligase domains within the same polypeptide.
      Whereas Nae I relaxes supercoiled DNA like a topoisomerase, even forming a
      transient covalent intermediate with the substrate DNA, Nae I shows no obvious
      sequence similarity to the topoisomerases. To further characterize the
      topoisomerase activity of Nae I, we report here that Nae I-43K changes the
      linking number of a single negatively supercoiled topoisomer of pBR322 by units
      of one and therefore is a type I topoisomerase. Positively supercoiled pBR322 was
      resistant to Nae I-43K. At low salt concentration Nae I-43K was processive; non
      saturating amounts of enzyme relaxed a fraction of the DNA. At high salt
      concentration the same non-saturating amounts of Nae I-43K partially relaxed all
      the DNA in a step-wise fashion to give a Gaussian distribution of topoisomers,
      demonstrating a switch from a processive to a distributive mode of action. Nae I
      43K decatenated kinetoplast DNA containing nicked circles, implying that Nae I
      43K can cleave opposite a nick. The products of the reaction are decatenated
      nicked circles under both processive and distributive conditions. The behavior of
      Nae I-43K is consistent with that of a prokaryotic type I topoisomerase.

PMID- 9580688
TI  - Escherichia coli ribosomal protein L3 stimulates the helicase activity of the
      Bacillus stearothermophilus PcrA helicase.
AB  - Escherichia coli ribosomal protein L3 stimulates the in vitro helicase activity
      of Bacillus stearothermophilus PcrA helicase upon a variety of different
      substrates. L3 has no intrinsic helicase or ATPase activity nor is it able to
      stimulate the ATPase activity of PcrA. Gel mobility shift assays revealed that
      the affinity of PcrA for a variety of different DNA species (single-stranded,
      nicked and 3'-tailed) was enhanced in the presence of L3. We suggest that the
      stimulatory effect of L3 upon the helicase activity of PcrA is mediated via a
      protein-protein interaction which promotes cooperative binding of PcrA to its DNA
      substrate. This activity of L3 appears to be specific for PcrA helicase.

PMID- 9580690
TI  - Solution structure of duplex DNA containing an extrahelical abasic site analog
      determined by NMR spectroscopy and molecular dynamics.
AB  - Translesional DNA synthesis past abasic sites proceeds with the preferential
      incorporation of dAMP opposite the lesion and, depending on the sequence context,
      one or two base deletions. High-resolution NMR spectroscopy and molecular
      dynamics simulations were used to determine the three-dimensional structure of a
      DNA heteroduplex containing a synthetic abasic site (tetrahydrofuran) residue
      positioned in a sequence that promotes one base deletions. Analysis of NMR
      spectra indicates that the stem region of the duplex adopts a right-handed
      helical structure and the glycosidic torsion angle is in anti orientation for all
      residues. NOE interactions establish Watson-Crick alignments for all canonical
      base pairs of the duplex. Measurement of distance interactions at the lesion site
      shows the abasic residue excluded from the helix. Restrained molecular dynamics
      simulations generated three-dimensional models in excellent agreement with the
      spectroscopic data. These structures show a regular duplex region and a slight
      bend at the lesion site. The tetrahydrofuran residue extrudes from the helix and
      is highly flexible. The model reported here, in conjunction with a previous study
      performed on abasic sites, explains the structural bias of one-base deletion
      mutations.

PMID- 9580691
TI  - Interaction of transcription factor YY1 with a replication-enhancing element,
      REE1, in an autonomously replicating human chromosome fragment.
AB  - We have previously shown that autonomous replication of human chromosome
      fragments is stimulated by the presence of an 18 bp sequence, REE1, which
      exhibits transcriptional silencer activity. The REE1 sequence is partly
      homologous with the serum response element (SRE) required for expression of the
      human c- fos gene. Here we have examined interaction of REE1 with human nuclear
      proteins using a gel retardation assay. One of the REE1-protein complexes formed
      showed almost the same mobility as the SRE-protein complex and complex formation
      was competitively inhibited by the SRE fragment. The protein complex with REE1 as
      well as that with SRE was found to contain the transcription factor YY1, known to
      bind to the SRE. These results suggest that YY1 protein may participate in
      stimulation of replication through its interaction with REE1.

PMID- 9580692
TI  - Rapid design of denaturing gradient-based two-dimensional electrophoretic gene
      mutational scanning tests.
AB  - With the current rapid pace at which human disease genes are identified there is
      a need for practical, cost-efficient genetic screening tests. Two-dimensional
      electrophoretic separation of PCR-amplified gene fragments on the basis of size
      and base pair sequence, in non-denaturing and denaturing gradient polyacrylamide
      gels respectively, provides a rapid parallel approach to gene mutational
      scanning. Accuracy of the denaturing gradient gel electrophoresis (DGGE)
      component of this system strongly depends on the design of the PCR primers and
      the melting characteristics of the fragments they encompass. We have developed a
      fully automated generally applicable procedure to generate optimal two
      dimensional test designs at a minimum amount of time and effort. Designs were
      generated for the RB1 , TP53 , MLH1 and BRCA1 genes that can be readily
      implemented in research and clinical laboratories as low cost genetic screening
      tests.

PMID- 9580693
TI  - High level transactivation by the ecdysone receptor complex at the core
      recognition motif.
AB  - Ecdysteroid signaling in insects is mediated by the ecdysone receptor complex
      that is composed of a heterodimer of the ecdysone receptor and Ultraspiracle. The
      DNA binding specificity plays a critical role of defining the repertoire of
      target genes that respond to the hormone. We report here the determination of the
      preferred core recognition motif by a binding site selection procedure. The
      consensus sequence consists of a perfect palindrome of the heptameric half-site
      sequence GAGGTCA that is separated by a single A/T base pair. No binding polarity
      of the ecdysone receptor/Ultraspiracle heterodimer to the core recognition motif
      was observed. This core motif mediated the highest level of ligand-induced
      transactivation when compared to a series of synthetic ecdysone response elements
      and to the natural element of the Drosophila hsp27 gene. This is the first report
      of a palindromic sequence identified as the highest affinity DNA binding site for
      a heterodimeric nuclear hormone receptor complex. We further present evidence
      that the ligand of the ecdysone receptor preferentially drives Ultraspiracle from
      a homodimer into a heterodimer. This mechanism might contribute additionally to a
      tight control of target gene expression.

PMID- 9580694
TI  - Meiotic double-strand breaks in yeast artificial chromosomes containing human
      DNA.
AB  - Meiotic recombination in the yeast Saccharomyces cerevisiae is initiated by
      double-strand breaks (DSB) in chromosomal DNA. These DSB, which can be mapped in
      the rad 50S mutant yeast strain, are caused by a topoisomerase II-like enzyme,
      the protein Spo11. Evidence suggests that this protein is located in the axial
      element of the meiotic chromosome which implies that the DSB are located in these
      chromosomes in the vicinity of the bases of the DNA loops. We have found that in
      the yeast artificial chromosomes carrying human DNA, at the level of resolution
      obtained by pulsed field gel electrophoresis (PFGE), the meiotic DSB in the
      diploid yeast are co-localized with the DNase I hypersensitive sites (HS) in a
      haploid strain of yeast. These HS are located close to sequences which, under
      stress, have the potential to form secondary structures containing unpaired
      nucleotides. Clusters of such sequences could be a hallmark of the bases of the
      chromatin loops.

PMID- 9580695
TI  - c-Myc gene single-strand binding protein-1, MSSP-1, suppresses transcription of
      alpha-smooth muscle actin gene in chicken visceral smooth muscle cells.
AB  - The expression of alpha-smooth muscle actin is coordinately regulated by positive
      and negative cis- elements in the promoter region. Although cis -elements and
      trans -acting factors involved in the positive regulation of the alpha-smooth
      muscle (alpha-SM) actin gene have been well characterized, details of negative
      regulation remain unclear. In functional analyses using cultured gizzard smooth
      muscle cells, we identified a sequence ranging from -238 to -219 in the promoter
      region as a novel negative element. Mutation and deletion analyses further
      revealed that a sequence, TATCTTA (-228 to -222), is essential for negative
      regulation. Gel shift assay and Southwestern blotting indicated that a nuclear
      protein factor specifically interacts with single- or double-strand DNA including
      this sequence, and the protein factor displays a highly potent binding to the
      sense strand DNA. cDNA cloning and gel shift analysis using anti-MSSP-1
      antibodies revealed that this protein factor is a chicken homolog of human MSSP-1
      (c- myc gene single-strand binding protein-1). In fact, overexpression of MSSP-1
      in cultured smooth muscle cells suppresses the promoter activity. These results
      suggest a novel function of MSSP-1 regarding the transcriptional regulation of
      alpha-sm actin gene.

PMID- 9580696
TI  - Analysis of sequences and predicted structures required for viral satellite RNA
      accumulation by in vivo genetic selection.
AB  - In vivo genetic selection was used to study the sequences and structures required
      for accumulation of subviral sat-RNA C associated with turnip crinkle virus
      (TCV). This technique is advantageous over site-specific mutagenesis by allowing
      side-by-side selection from numerous sequence possibilities as well as sequence
      evolution. A 22 base hairpin and 6 base single-stranded tail located at the 3'
      terminus of sat-RNA C were previously identified as the promoter for minus strand
      synthesis. Approximately 50% of plants co-inoculated with TCV and sat-RNA C
      containing randomized sequence in place of the 22 base hairpin accumulated sat
      RNA in uninoculated leaves. The 22 base region differed in sat-RNA accumulating
      in all infected plants, but nearly all were predicted to fold into a hairpin
      structure that maintained the 6 base tail as a single-stranded sequence. Two
      additional rounds of sat-RNA amplification led to four sequence family 'winners',
      with three families containing multiple variants, indicating that evolution of
      these sequences was occurring in plants. Three of the four sequence family
      winners had the same 3 bp at the base of the stem as wild-type sat-RNA C. Two of
      the winners shared 15 of 22 identical bases, including the entire stem region and
      extending two bases into the loop. These results demonstrate the utility of the
      in vivo selection approach by showing that both sequence and structure contribute
      to a more active 3'-end region for accumulation of sat-RNA C.

PMID- 9580697
TI  - Upf1 and Upf2 proteins mediate normal yeast mRNA degradation when translation
      initiation is limited.
AB  - mRNA degradation is coupled with the process of mRNA translation. For example, an
      mRNA molecule, on which translation is prematurely terminated because of a
      nonsense codon, may be rapidly degraded. This nonsense-mediated mRNA decay in the
      yeast Saccharomyces cerevisiae is mediated by the Upf1 and Upf2 proteins. Yeast
      mRNAs can also be selectively destabilized by limiting the rate of translation
      initiation. Two such destabilized mRNAs, from the SSA1 and SSA2 genes, have been
      identified using temperature-sensitive mutations affecting the Prt1 component of
      eukaryotic initiation factor 3. For SSA1 and SSA2 mRNAs, and for structurally
      modified SSA mRNA derivatives, I show here that degradation is triggered when
      translation initiation is limited but ongoing. This initiation-dependent mRNA
      degradation is limited to a subset of mRNAs that includes at least those from the
      SSA1 and SSA2 genes, and occurs through Upf1- and Upf2-mediated processes,
      although sequence elements characteristic of nonsense-mediated decay are not
      evident in these mRNAs.

PMID- 9580699
TI  - Sp1, but not Sp3, functions to mediate promoter activation by TGF-beta through
      canonical Sp1 binding sites.
AB  - Transforming growth factor beta (TGF-beta) causes growth arrest at the G1 phase
      of the cell cycle in most cell types. Both the cyclin dependent kinase inhibitor
      p15(INK4B) and p21(Cip1/WAF1) genes have been found to be induced by TGF-beta in
      human keratinocyte HaCaT cells. Analyses of the human p15 and p21 promoters have
      led to the identification of GC-rich sequences capable of binding to Sp1
      transcription factors as necessary elements for the TGF-beta induction of both
      promoters. We report here that canonical Sp1 binding sites derived from the SV40
      21 bp repeat could also support promoter induction by TGF-beta when placed
      upstream of a minimal luciferase reporter construct containing only the TATA and
      Inr elements. Gel retardation assays identified Sp1, Sp3 and DeltaSp3 as major
      factors binding to the canonical Sp1 sites in HaCaT cells and that TGF-beta
      treatment did not change their binding activities over a 24 h period. More
      importantly, GAL4-Sp1, but not GAL4-Sp3, chimeric protein supported TGF-beta
      mediated gene induction from a luciferase reporter construct driven by five GAL4
      DNA binding sites. Our results suggest that Sp1 binding site can function as a
      distinct TGF-beta responsive element for TGF-beta mediated promoter expression
      and Sp1 per se can mediate this response.

PMID- 9580698
TI  - Heterologous complementation reveals that mutant alleles of QSR1 render 60S
      ribosomal subunits unstable and translationally inactive.
AB  - QSR1 is a highly conserved gene which encodes a 60S ribosomal subunit protein
      that is required for joining of large and small ribosomal subunits. In this
      report we demonstrate heterologous complementation of a yeast QSR1 deletion
      strain with both the human and corn homologs and show that the human and corn
      proteins are assembled into hybrid yeast/human and yeast/corn ribosomes. While
      the homologous genes complement lethality of the QSR1 deletion, they also result
      in a diminished growth rate. Analyses of the translation rates of ribosomes
      containing the human and corn proteins reveal a partial loss of function.
      Velocity gradient analyses of the hybrid ribosomes after exposure to high
      concentrations of salt indicate that the decreased activity is due to lability of
      the hybrid 60S subunits.

PMID- 9580700
TI  - Oligomeric properties and DNA binding specificities of repressor isoforms from
      the Streptomyces bacteriophage phiC31.
AB  - Three protein isoforms (74, 54 and 42 kDa) are expressed from repressor gene c in
      the Streptomyces temperate bacteriophage phiC31. Because expression of the two
      smaller isoforms, 54 and 42 kDa, is sufficient for superinfection immunity, the
      interaction between these isoforms was studied. The native 42 kDa repressor
      (Nat42) and an N-terminally 6x histidine-tagged 54 kDa isoform (His54) were shown
      by co-purification on a Ni-NTA column to interact in Streptomyces lividans . In
      vitro three repressor preparations, containing Nat42, His54 and the native 54 and
      42 kDa isoforms expressed together (Nat54&42), were subjected to chemical
      crosslinking and gel filtration analysis. Homo- and hetero-tetramers were
      observed. Previous work showed that the smallest isoform bound to 17 bp operators
      containing aconservedinvertedrepeat (CIR) and that the CIRs were located at 16
      loci throughout the phiC31 genome. One of the CIRs (CIR6) is believed to be
      critical for regulating the lytic pathway. The DNA binding activities of the
      three repressor preparations were studied using fragments containing CIRs (CIR3
      CIR6) from the essential early region as templates for DNase I footprinting.
      Whereas Nat42 bound to CIR6, poorly to CIR5 but undetectably to CIR3 or CIR4, the
      Nat54&42 preparation could bind to all CIRs tested, albeit poorly to CIR3 and
      CIR4. The His54 isoform bound all CIRs tested. Isoforms expressed from the phiC31
      repressor gene, like those which are expressed from many eukaryotic transcription
      factor genes, apparently have different binding specificities.

PMID- 9580701
TI  - Adjacent proline residues in the inhibitory domain of the Oct-2 transcription
      factor play distinct functional roles.
AB  - A 40 amino acid region of Oct-2 from amino acids 142 to 181 functions as an
      active repressor domain capable of inhibiting both basal activity and activation
      of promoters containing a TATA box, but not of those that contain an initiator
      element. Based on our observation that the equivalent region of the closely
      related Oct-1 factor does not act as an inhibitory domain, we have mutated
      specific residues in the Oct-2 domain in an attempt to probe their importance in
      repressor domain function. Although mutations of several residues have no or
      minimal effect, mutation of proline 175 to arginine abolishes the ability to
      inhibit both basal and activated transcription. In contrast, mutation of proline
      174 to arginine confers upon the domain the ability to repress activation of an
      initiator-containing promoter by acidic activation domains, and also suppresses
      the effect of the proline 175 mutation. Hence, adjacent proline residues play key
      roles in the functioning of the inhibitory domain and in limiting its specificity
      to TATA-box-containing promoters.

PMID- 9580702
TI  - Crystal structures of B-DNA with incorporated 2'-deoxy-2'-fluoro-arabino
      furanosyl thymines: implications of conformational preorganization for duplex
      stability.
AB  - The fundamental conformational states of right-handed double helical DNA, the A-
      and B-forms, are associated with distinct puckers of the sugar moieties. The
      furanose conformation itself is affected by the steric and electronic nature of
      the ring substituents. For example, a strongly electronegative substituent at the
      C2' position, such as in the 2'-deoxy-2'-fluoro ribo furanosyl analogue, will
      drive the conformational equilibrium towards the C3'- endo type (north).
      Conversely, the 2'-deoxy-2'-fluoro arabino furanosyl modification with opposite
      stereochemistry at C2' appears to have a preference for a C2'- endo type pucker
      (south). Incorporation of 2'-fluoroarabinofuranosyl thymines was previously shown
      to enhance the thermodynamic stability of B-DNA duplexes. We have determined the
      crystal structures of the B-DNA dodecamer duplexes [d(CGCGAASSCGCG)]2and
      [d(CGCGAASTCGCG)]2with incorporated 2'-deoxy-2'-fluoroarabinofuranosyl thymines S
      (south) at 1.55 A resolution. In the crystal structures, all S residues adopt an
      O4'- endo conformation (east), well compatible with an overall B-form duplex
      geometry. In addition to the increased rigidity of S nucleosides, a clathrate
      like ordered water structure around the 2'-fluorines may account for the observed
      larger thermodynamic stability of DNA duplexes containing 2'-deoxy-2'
      fluoroarabino thymidines.

PMID- 9580704
TI  - Sequencing DNA using mass spectrometry for ladder detection.
AB  - Sequencing of DNA fragments of 130 and 200 bp using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry for DNA ladder detection
      was demonstrated. With further improvement in mass resolution and detection
      sensitivity, mass spectrometry shows great promise for routine DNA sequencing in
      the future.

PMID- 9580703
TI  - DNA condensation for gene therapy as monitored by atomic force microscopy.
AB  - The atomic force microscope (AFM) was used to assay the extent of DNA
      condensation in approximately 100 different complexes of DNA with polylysine (PL)
      or PL covalently attached to the glycoproteins asialoorosomucoid (AsOR) or
      orosomucoid (OR). The best condensation of DNA was obtained with 10 kDa PL
      covalently attached to AsOR, at a lysine:nucleotide (Lys:nt) ratio of 5:1 or
      higher. These conditions produce large numbers of toroids and short rods with
      contour lengths of 300-400 nm. Some DNA condensation into shortened thickened
      structures was seen with 10 kDa PL attached to AsOR at Lys:nt ratios of 1.6:1 and
      3:1. Some DNA condensation was also seen with 4 kDa PL at Lys:nt ratios of 3:1
      and higher. Little DNA condensation was seen with PL alone or with PL convalently
      attached to OR at Lys:nt ratios up to 6:1. AsOR-PL enhanced gene expression in
      the mouse liver approximately 10- to 50-fold as compared with PL alone.

PMID- 9580705
TI  - Multiple parameters determine the specificity of transcriptional response by
      nuclear receptors HNF-4, ARP-1, PPAR, RAR and RXR through common response
      elements.
AB  - A number of nuclear receptors, including retinoic acid receptors (RARs), retinoid
      X receptors (RXRs), hepatocyte nuclear factor 4 (HNF-4), chicken ovalbumin
      upstream promoter transcription factor I (COUP-TFI), apolipoprotein regulatory
      protein 1 (ARP-1) and peroxisome proliferator-activated receptor (PPAR), bind to
      response elements comprised of two core motifs, 5'-RG(G/T)TCA, or a closely
      related sequence separated by 1 nt (DR1 elements). The potential role of the
      precise sequence of the core motif as well as the spacer nucleotide in
      determining specificity and promiscuity of receptor-response element interactions
      was investigated. We show here that nucleotides at base positions 1, 2 and 4 of
      the core motif as well as the spacer nucleotide determine the binding preference
      of HNF-4 and ARP-1 homodimers and RAR:RXR and PPAR:RXR heterodimers. In
      transfection experiments transcriptional activation by HNF-4 and PPAR:RXR and
      repression by ARP-1 correlated with the relative in vitro binding affinity
      provided the element was located within the proper promoter context. Furthermore,
      promoter context also determined whether an element that binds to HNF-4 and
      PPAR:RXR with equal affinity functions as an HNF-4 response element or PPAR
      response element. Thus, apart from the element-specific differences in affinity
      for the receptors, additional promoter-specific transcription factors that
      interact with HNF-4 and PPAR:RXR determine the specificity of transcriptional
      response through DR1-type elements.

PMID- 9580707
TI  - Oligoribonucleotide circularization by 'template-mediated' ligation with T4 RNA
      ligase: synthesis of circular hammerhead ribozymes.
AB  - Circular hammerhead ribozymes were synthesized from linear oligoribonucleotides
      using T4 RNA ligase. Some of the precursors could not be efficiently circularized
      under standard conditions. For these molecules, the use of a DNA template allowed
      their efficient circularization. The template was designed to prevent the
      precursor from folding into an unsuitable structure. The template allowed
      circular ribozymes as small as 15 nucleotides in length to be efficiently
      synthesized at concentrations as high as 50 microM in the ligation reaction. The
      circular products retained their biological activity.

PMID- 9580706
TI  - Preparation of active tRNA gene transcripts devoid of 3'-extended products and
      dimers.
AB  - Significant amounts (10-30%) of 3'-extended products with one or two extra
      nucleotides are synthesized in the course of run-off tRNA gene transcription with
      T7 RNA polymerase. Denaturing polyacrylamide gel electrophoresis appeared to be
      insufficient to provide preparative amounts of pure correct-size transcripts.
      Formation of dimers by tRNA gene transcripts as side products in the course of
      their activation is also another obstacle in preparation of biologically active
      transcripts. Here, we have shown that EF-Tu affinity chromatography and/or non
      denaturing electrophoresis are simple and efficient tools for isolation of highly
      active correct-size transcripts. Conditions for transcript activation in vitro
      should be carefully controlled to prevent dimer formation and obtain reliable
      data on tRNA transcript structure and function.

PMID- 9580708
TI  - Direct visualization of site-specific and strand-specific DNA methylation
      patterns in automated DNA sequencing data.
AB  - We report here a simple method of directly visualizing in automated DNA
      sequencing chromatograms DNA methylations of different types including cytosine
      methylations in Hpa II and dcm sites as well as adenine methylations in dam
      sites. This is made possible by the observation that the extent of incorporation
      of fluorescently labeled dideoxynucleotides is influenced by the methylated bases
      in template DNA. This simple approach involves routine automated DNA sequencing
      without any prior treatment of DNA specific for detecting DNA methylation.

PMID- 9580710
TI  - A role for academic medical centers in the era of managed care: immediate,
      interactive, free information.

PMID- 9580709
TI  - New positive/negative selectable markers for mammalian cells on the basis of
      Blasticidin deaminase-thymidine kinase fusions.
AB  - Two positive and negative selectable markers were created for use in mammalian
      cells. They are based on two genes for the resistance to Blasticidin S (BlaS) and
      on the thymidine kinase (Tk) gene of herpes simplex virus (HSV). The markers can
      be selected positively by their ability to induce BlaS resistance and negatively
      on the induced sensitivity towards gancyclovir (GANC). Both constructs are also
      expressed in Escherichia coli and transfer BlaS resistance to this organism as
      well, making these markers very suitable for the construction of shuttle vectors.

PMID- 9580711
TI  - Medical students' empathic understanding of their patients.

PMID- 9580712
TI  - Fundamentals of financial statement analysis for academic physician managers.
AB  - Academic medical centers (i.e., teaching hospitals) and academic medical
      practices are under pressure to control costs to compete with for-profit health
      care institutions. The authors explain how academic physician managers who want
      to control costs wisely must first understand the cost structure of the medical
      center or practice and compare that structure with those of for-profit
      institutions. Doing this requires a firm understanding of how to use a valuable
      tool, financial statement analysis, to assess an institution's health and
      performance. Such analysis consists of calculating a variety of financial ratios
      (e.g., operating income divided by revenues; net income divided by total assets)
      and then comparing them with the corresponding ratios that are considered
      industry norms. Three types of financial statements (defined in detail) lend
      themselves to this approach: the balance sheet, income statement, and statement
      of cash flows. The authors define standard financial ratios, point out their uses
      and limitations, and emphasize that a ratio's meaning derives from comparing it
      with the corresponding benchmark ratio in the industry as a whole. Ratios should
      be used not as the end point of assessing financial status, but as ways to
      identify possible problems that require further investigation. Analysis of trends
      of ratios over time within an institution is a complementary approach. The
      authors then discuss the use of ratios in three standard types of institutional
      evaluation: of performance, of liquidity and leverage, and of strategic planning.
      In addition, they present the financial statement of a fictitious academic
      medical center as an example of how to use ratios for financial statement
      analysis. The authors emphasize that the key to using the ratios they discuss and
      hundreds of others is first to decide what question needs answering and then to
      choose the relevant ratios to provide a basis for finding the answer.

PMID- 9580713
TI  - Defining teaching hospitals' GME strategy in response to new financial and market
      challenges.
AB  - The authors present an overview of current graduate medical education (GME)
      issues, particularly the financial challenges to teaching hospitals resulting
      from the Balanced Budget and Tax Payer Relief Acts of 1997 and other recent
      market-driven factors. They describe in detail the nature of Medicare GME
      payments before and after the 1997 legislation, with specific examples, and
      explain the negative financial impact of the legislation and aspects of the
      legislation that are designed to alleviate that impact. Other factors influencing
      GME program size and composition are also discussed, including oversupplies or
      shortages of physicians, the concern that teaching hospitals are using public
      funds to train international medical graduates, changing training requirements,
      etc. The authors also describe a recent consulting assignment during which they
      assisted a major teaching hospital to develop a GME strategy that was responsive
      to the organization's mission and patients and that took into account future GME
      financing challenges. Detailed explanations are given of how the consultants
      analyzed the hospital's GME programs and finances, developed and ranked key
      institution-specific program criteria (strategic, organizational and operational,
      and financial), and, in consultation with all key stakeholders, formulated a GME
      strategy specific to the institution's needs. The authors conclude by cautioning
      that each institution's GME strategy will be different, but that it is important
      for institutions to develop such strategies to better face future challenges.

PMID- 9580714
TI  - What should we do about Eduard Pernkopf's atlas?
AB  - Eduard Pernkopf created a classic anatomy atlas during World War II. He was also
      an ardent Nazi. Questions have been raised recently about the propriety of using
      an atlas created by a Nazi and illustrated by dissections of cadavers whose
      identities are unknown, but who could have been victims of Nazi political terror.
      To examine the ethical issues involved, the author first reviews recently
      published work regarding Pernkopf and his atlas, with the caution that facts are
      few in a debate where emotions run high and opinions abound. He then considers
      what has been written by bioethicists on the use of scientific data from the Nazi
      era and how those arguments might apply to Pernkopf and his atlas. Important
      questions remain, however. For example, are scientific data tainted by their
      associations with Nazism, or should such data (including the atlas) be assessed
      on their own merits, separate from the persons and ideologies involved in their
      creation? Finally, the author offers his own perspective as a young gross
      anatomist and physician. He argues that rejecting the hateful beliefs of Pernkopf
      and his fellow Nazis does not necessitate rejecting the elegant anatomic images
      they produced. The author further suggests that use of the atlas is itself the
      most fitting tribute to those who died for it, whether they were victims of Nazi
      repression or not. Those cadavers not only teach anatomy, they "can remind us of
      suffering not only in the past but in the present, that we may be more
      compassionate physicians, more compassionate citizens of the world."

PMID- 9580715
TI  - Strategies for improving teaching practices: a comprehensive approach to faculty
      development.
AB  - Medical school faculty members are being asked to assume new academic duties for
      which they have received no formal training. These include time-efficient
      ambulatory care teaching, case-based tutorials, and new computer-based
      instructional programs. In order to succeed at these new teaching tasks, faculty
      development is essential. It is a tool for improving the educational vitality of
      academic institutions through attention to the competencies needed by individual
      teachers, and to the institutional policies required to promote academic
      excellence. Over the past three decades, strategies to improve teaching have been
      influenced by the prevailing theories of learning and research on instruction,
      which are described. Research on these strategies suggests that workshops and
      students' ratings of instruction, coupled with consultation and intensive
      fellowships, are effective strategies for changing teachers' actions. A
      comprehensive faculty development program should be built upon (1) professional
      development (new faculty members should be oriented to the university and to
      their various faculty roles); (2) instructional development (all faculty members
      should have access to teaching-improvement workshops, peer coaching, mentoring,
      and/or consultations); (3) leadership development (academic programs depend upon
      effective leaders and well-designed curricula; these leaders should develop the
      skills of scholarship to effectively evaluate and advance medical education); (4)
      organizational development (empowering faculty members to excel in their roles as
      educators requires organizational policies and procedures that encourage and
      reward teaching and continual learning). Comprehensive faculty development, which
      is more important today than ever before, empowers faculty members to excel as
      educators and to create vibrant academic communities that value teaching and
      learning.

PMID- 9580716
TI  - Course-based assessment: implementing outcome assessment in medical education.
AB  - Rapid, intensive change in the health care system requires a change in how the
      outcomes of medical education are measured. The post-Flexner model of evaluating
      the institution focuses on teaching (rather than learning) and is not relevant to
      ambulatory training. Medical education needs to use assessment that focuses on
      student learning, can respond quickly to changes, and is continuously refined by
      use of information about students' abilities. Course-based assessment is a
      systematic way to gather, analyze, disseminate, and use course data to improve
      student learning, and it is well suited to current trends in health professions
      education. The authors present and discuss six principles of effective outcome
      assessment in medical education and illustrate these principles from their
      experience of using this type of assessment in a pre-clinical course integrating
      basic science, social science, and clinical skills. Courses and programs for
      medical students and residents should use course-based assessment to ensure that
      medical trainees acquire the skills and attitudes needed to practice medicine
      well. The next challenge for medical educators is to implement course-based
      assessment that is intimately tied to a broader institutional plan.

PMID- 9580717
TI  - Beyond curriculum reform: confronting medicine's hidden curriculum.
AB  - Throughout this century there have been many efforts to reform the medical
      curriculum. These efforts have largely been unsuccessful in producing fundamental
      changes in the training of medical students. The author challenges the
      traditional notion that changes to medical education are most appropriately made
      at the level of the curriculum, or the formal educational programs and
      instruction provided to students. Instead, he proposes that the medical school is
      best thought of as a "learning environment" and that reform initiatives must be
      undertaken with an eye to what students learn instead of what they are taught.
      This alternative framework distinguishes among three interrelated components of
      medical training: the formal curriculum, the informal curriculum, and the hidden
      curriculum. The author gives basic definitions of these concepts, and proposes
      that the hidden curriculum needs particular exploration. To uncover their
      institution's hidden curricula, he suggests that educators and administrators
      examine four areas: institutional policies, evaluation activities, resource
      allocation decisions, and institutional "slang." He also describes how
      accreditation standards and processes might be reformed. He concludes with three
      recommendations for moving beyond curriculum reform to reconstruct the overall
      learning environment of medical education, including how best to move forward
      with the Medical School Objectives Project sponsored by the AAMC.

PMID- 9580718
TI  - "Patient informatics": creating new partnerships in medical decision making.
AB  - The amassing of health information on the Internet and World Wide Web continues
      unabated. Patients anxious to participate in decisions about their own treatment
      have turned to the Internet to confirm diagnoses, validate physician-recommended
      treatment, or seek alternative therapies. While increased information for
      patients has been linked to improved outcomes, there are inherent dangers
      associated with the kind of unauthenticated information available on the Web. The
      authors discuss the nature of these dangers as well as review the advantages for
      patients of "information therapy" (improved access to health information). They
      also examine how the Internet has begun to affect the physician-patient
      relationship, and describe how the Internet and information technology can be
      effectively used by physicians in patient care. They recommend that the academic
      health sciences community seize the opportunity to take the lead in ensuring that
      patients have access to reliable health information, and suggest that "patient
      informatics" be integrated by academic physicians and educators into the teaching
      of clinical skills.

PMID- 9580719
TI  - The preparedness of students to discuss end-of-life issues with patients.
AB  - PURPOSE: To explore how well medical schools prepare students to address end-of
      life issues with their patients. METHOD: In 1997, the authors surveyed 226 fourth
      year students at Georgetown University School of Medicine and Mayo Medical
      School, assessing relevant knowledge, experiences, and attitudes, and the
      students' sense of preparedness to address end-of-life issues. RESULTS: Seventy
      two percent (162) of the eligible students responded. Almost all (99%) recognized
      the importance of advance directives and anticipated discussing end-of-life
      issues with patients in their practices (84%). However, only 41% thought their
      education regarding end-of-life issues had been adequate, only 27% had ever
      discussed end-of-life issues with a patient themselves, and only 35% thought they
      had had adequate exposure and education regarding advance directives. Eighty
      percent favored more education about end-of-life issues. Educational exposure to
      end-of-life issues and to role models, ability to correctly define an advance
      directive, number of end-of-life discussions witnessed, and age all were
      associated the students' sense of preparedness to discuss advance directives with
      patients. CONCLUSION: Most of the students felt unprepared to discuss end-of-life
      issues with their patients, but wanted to learn more. The factors associated with
      a sense of preparedness suggest several possible, easily made, educational
      interventions, but further research is required to understand the scope of the
      problem and to implement curricular modifications.

PMID- 9580720
TI  - Does training location influence the clinical skills of medical students?
AB  - PURPOSE: To examine the benefits of the shift of medical education into
      ambulatory primary care settings by investigating whether medical students
      exposed to a common primary care problem (low back pain) in ambulatory care
      settings develop better clinical skills. METHOD: In 1995, the authors categorized
      420 students from all four North-Carolina medical schools into groups that had
      previously encountered patients with low back pain in ambulatory primary care
      settings, tertiary care settings, both, or neither. The clinical skills of the
      groups were determined using data collected during standardized-patient
      examination in which students took the history of, physically examined, and chose
      a diagnostic strategy for patients with acute, uncomplicated low back pain.
      RESULTS: In general, there was no difference between the performances of the
      student groups associated with the settings of their previous encounters with low
      back pain. On average, the students failed to ask 35% of the history items and
      failed to perform 35% of the physical examination items. Many students chose
      inappropriate diagnostic strategies. CONCLUSION: The lack of difference between
      the groups' clinical performances indicates a need to more rigorously define and
      evaluate outcomes of education in ambulatory care settings. The generally poor
      clinical performance of all groups suggests that the current curriculum
      inadequately teaches clinical skills needed to assess and manage common problems.
      Clearer expectations of competencies and assurances that preceptors in ambulatory
      care settings will help students meet those learning objectives might lead to
      better outcomes.

PMID- 9580721
TI  - The effect at one teaching hospital of interns' workloads on the satisfaction of
      their patients.
AB  - PURPOSE: To explore whether the amount of workload of first-year residents
      (interns) affects the satisfaction of their patients. METHOD: The authors
      collected data from January through May 1995 for 145 patients admitted to
      Lexinton Veterans Affairs Medical Center with the primary diagnosis of chronic
      obstructive pulmonary disease (COPD) or congestive heart failure (CHF). Workload
      was measured as the number of other patients for whom the intern had primary
      responsibility on the day of the studied patient's admission. A questionnaire
      measured the patients' satisfaction on the day of discharge. The authors analyzed
      the data using Pearson correlation and multiple linear regression. RESULTS: For
      the 89 patients with COPD (controlling for patient age, severity of illness, and
      sex of intern), greater workloads for their interns was a significant predictor
      of decreased patients' satisfaction (p = .001). No association was found for the
      56 patients with CHF. CONCLUSION: Interns' workloads on the day their patients
      are admitted can influence their patients' subsequent satisfaction.

PMID- 9580722
TI  - Relationship between early clinical exposure and first-year students' attitudes
      toward medical education.
AB  - PURPOSE: To determine whether there is a relationship between early clinical
      exposure and students' attitudes toward medical education. METHOD: At the end of
      the spring quarter, 1995, 93 first-year students at the University of Washington
      School of Medicine were asked to complete a one-page, 15-item questionnaire. The
      11 items in the questionnaire's first section assessed the students' attitudes
      toward medical education; each item was rated on a five-point Likert scale (1 =
      strongly agree, 5 = strongly disagree). The four items in the second section
      assessed the students' clinical exposures, including type, frequency, and
      duration. RESULTS: In all, 86 of the students (92%) returned completed
      questionnaires. The students' participation in clinical experiences was, overall,
      much higher than expected. A total of 77 students (90%) reported some form of
      clinical exposure. The clinical-exposure group was defined as those students who
      had participated in a preceptorship for at least one academic quarter (a half-day
      per week in clinic) or who had at least five days of clinical experience.
      Significance tests revealed that the students in the clinical-exposure group were
      more satisfied with their medical education than were the other students (p =
      .009). The students' attitudes toward medical education were generally favorable,
      regardless of their clinical exposures. However, approximately one fourth of the
      class expressed discontent with the process of medical education, and 40%
      indicated they were more cynical than when they had started school. CONCLUSION:
      The results of this study suggest that early clinical experience may contribute
      to students' satisfaction with medical education.

PMID- 9580723
TI  - Influence of medical school on medical students' opinions about primary care
      practice.
AB  - PURPOSE: To compare first- and fourth-year medical students' opinions about
      primary care practice. METHOD: A cross-sectional survey was made of medical
      students at New York Medical College (NYMC) and East Carolina University School
      of Medicine (ECUSOM) over three years (1993-94, 1994-95, and 1995-96). Three
      consecutive classes of first-year students from both schools (n = 807), two
      consecutive classes of fourth-year NYMC students (n = 373), and three consecutive
      classes of fourth-year ECUSOM students (n = 221) were given a self-administered
      questionnaire about professional aspects of primary care practice. Responses to
      ten items about primary care practice were the independent variables in a
      logistic regression analysis. Career choice, categorized as primary care or non
      primary care, was the dependent variable. Independent, two-tailed t-tests were
      employed to compare the responses of the first-year students interested in
      primary care careers with those of the fourth-year students interested in primary
      care careers. RESULTS: In all, 639 (79%) of the first-year students and 396 (67%)
      of the fourth-year students returned completed questionnaires. The first-year
      students interested in primary care careers were significantly more likely to
      believe that primary care practice has more prestige, has more intellectual
      stimulation, needs a large knowledge base, and involves work that is more
      important than that of non-primary care physicians, and were significantly more
      likely to disagree with the assertion that in primary care practice, physicians
      have more control over their working hours. With one exception (prestige of
      primary care practice), all these independent variables were significant for the
      fourth-year students as well. The comparison of the first- and fourth-year
      students indicated that the fourth-year students were significantly more likely
      to believe that primary care practice has more intellectual stimulation, needs a
      large knowledge base, and requires knowledge that non-primary care practice may
      not; they were also significantly more likely to disagree with the assertions
      that primary care practice is adequately compensated, has more prestige, and
      allows more control over working hours. CONCLUSION: It appears that students'
      positive perceptions about primary care practice may change as realistic
      perceptions about the professional demands on primary care physicians develop
      during medical school.

PMID- 9580724
TI  - Attitudes of physicians practicing in New Mexico toward gay men and lesbians in
      the profession.
AB  - PURPOSE: To examine the attitudes of physicians practicing in New Mexico toward
      gay and lesbian medical students, house officers, and physician colleagues.
      METHOD: In May 1996, the authors mailed a questionnaire with demographic and
      attitude questions to 1,949 non-federally employed physicians practicing in New
      Mexico. The questionnaire consisted of questions dealing with medical school
      admission, residency training, and referrals to colleagues. The response rate was
      53.6%. RESULTS: Of all the responding physicians, 4.3% would refuse medical
      school admission to applicants known to be gay or lesbian. Respondents were most
      opposed to gay and lesbian physicians' seeking residency training in obstetrics
      and gynecology (10.1%), and least opposed to their seeking residency training in
      radiology (4.3%). Disclosure of homosexual orientation would also threaten
      referrals to gay and lesbian obstetrician-gynecologists (11.4%) more than to gay
      or lesbian physicians in other specialties. CONCLUSION: Physicians' attitudes
      toward gay and lesbian medical students, house officers, and physician colleagues
      seem to have improved considerably from those reported previously in the
      literature. However, gay men and lesbians in medicine continue to face opposition
      in their medical training and in their pursuit of specialty practice.

PMID- 9580725
TI  - Does teaching medical students in the office affect the way physicians complete
      patient-encounter forms?
AB  - PURPOSE: To determine whether teaching medical students has concurrent economic
      effects on physicians and their practices. METHOD: The authors reviewed 869
      patient-encounter forms completed in April 1994 and July 1995 by four family
      medicine physicians who were clinical faculty at the State University of New York
      Health Science Center at Syracuse. The authors compared those forms that were
      completed when a third-year medical student was present for the patient encounter
      with those completed when a student was not present. The authors looked for
      differences in the distributions of billing codes and in the frequencies of in
      office procedures performed and diagnostic tests ordered. RESULTS: The presence
      or absence of a third-year medical student had no significant effect on the
      variables studied. CONCLUSION: In the clinical settings studied, concurrent
      medical student teaching did not appear to affect the distribution of billing
      codes or the frequency of in-office procedures performed or diagnostic tests
      ordered.

PMID- 9580726
TI  - Physician workload: the rural perspective.

PMID- 9580727
TI  - A futile search.

PMID- 9580728
TI  - The torch is lit and burning, thank you!

PMID- 9580729
TI  - Questions about donepezil.

PMID- 9580730
TI  - Playing-related musculoskeletal disorders in musicians: a systematic review of
      incidence and prevalence.
AB  - BACKGROUND: Work-related musculoskeletal disorders cause pain, disability and
      loss of employment for many workers, including musicians. Although performing
      arts medicine is a growing field, the health problems of musicians remain under
      recognized and under-researched. Therefore, the author undertook a systematic
      review of published information on the incidence and prevalence of playing
      related musculoskeletal disorders (PRMDs) in classical musicians. METHODS: Seven
      databases were searched for the period 1980 to 1996. The main textbook and
      performing arts medicine journals were searched manually, as were reference lists
      of all relevant papers. The author also contacted individuals familiar with the
      literature of performing arts medicine. Studies were included for review if they
      reported PRMD incidence or prevalence in classical musicians. Of the 24 studies
      identified, 18 cross-sectional surveys and cohort studies were reviewed. The
      author subjectively assessed the studies using criteria modified from an existing
      evaluation scale and used 4 criteria for data combination. On the basis of
      prevalence values from the eligible studies, chi 2 tests for heterogeneity were
      performed. RESULTS: Only one study estimated PRMD incidence. Ten of the 17
      prevalence studies were ineligible for data combination, because of low response
      rates and other methodological problems. In the 7 eligible studies, PRMD point
      prevalence ranged from 39% to 87% in adult musicians and from 34% to 62% in
      secondary school music students. The best estimates of PRMD prevalence were
      derived from the 3 studies that excluded mild complaints; these studies indicated
      that PRMD prevalence was 39% and 47% in adults and 17% in secondary school music
      students respectively. Statistical combination of data across studies within each
      demographic category was not possible. INTERPRETATION: Available data indicate
      that the prevalence of PRMD in adult classical musicians is comparable to the
      prevalence of work-related musculoskeletal disorders reported for other
      occupational groups. Several recommendations for future research are outlined.

PMID- 9580731
TI  - Identifying unidentified recipients of HIV-infected blood.

PMID- 9580732
TI  - Unconventional therapies for cancer: 2. Green tea. The Task Force on Alternative
      Therapies of the Canadian Breast Cancer Research Initiative.

PMID- 9580733
TI  - Management of common musculoskeletal problems: a survey of Ontario primary care
      physicians.
AB  - BACKGROUND: In Canada, primary care physicians manage most musculoskeletal
      problems. However, their training in this area is limited, and some aspects of
      management may be suboptimal. This study was conducted to examine primary care
      physicians' management of 3 common musculoskeletal problems, ascertain the
      determinants of management and compare management with that recommended by a
      current practice panel. METHODS: A stratified computer-generated random sample of
      798 Ontario members of the College of Family Physicians of Canada received a self
      administered questionnaire by mail. Respondents selected various items in the
      management of 3 hypothetical patients: a 77-year-old woman with a shoulder
      problem, a 64-year-old man with osteoarthritis of the knee and a 30-year-old man
      with an acutely hot, swollen knee. Scores reflecting the proportion of
      recommended investigations, interventions and referrals selected for each
      scenario were calculated and examined for their association with physician and
      practice characteristics and physician attitudes. RESULTS: The response rate was
      68.3% (529/775 eligible physicians). For the shoulder problem, all of the
      recommended items were chosen by the majority of respondents. However, of the
      items not recommended, ordering blood tests was selected by almost half (242
      [45.7%]) as was prescribing an NSAID (236 [44.7%]). For the knee osteoarthritis
      the majority of respondents chose the recommended items except exercise (selected
      by only 175 [33.1%]). Of the items not recommended, tests were chosen by about
      half of the respondents and inappropriate referrals (chiefly for orthopedic
      surgery) were chosen by a quarter. For the acutely hot knee, the majority of
      physicians chose all of the recommended items except use of ice or heat (selected
      by only 188 [35.6%]). Although most (415 [78.5%]) of the respondents selected the
      recommended joint aspiration for this scenario, 84 (15.9%) omitted this
      investigation or referral to a specialist. The selection of recommended items was
      strongly associated with training in musculoskeletal specialties during medical
      school and residency. INTERPRETATION: Primary care physicians' management of 3
      common musculoskeletal problems was for the most part in accord with panel
      recommendations. However, the unnecessary use of diagnostic tests, inappropriate
      prescribing of NSAIDs, low use of patient-centred options such as exercise, and
      lack of diagnostic suspicion of infectious arthritis are cause for concern. The
      results point to the need for increased exposure to musculoskeletal problems
      during undergraduate and residency training and in continuing medical education.

PMID- 9580735
TI  - Undergraduate and postgraduate medical education in Canada.
AB  - An overview of medical education at both the undergraduate and postgraduate
      levels in Canadian faculties of medicine is provided. Particular attention is
      focused on changes that have occurred in the 1990s and their effect on medical
      students and on educational programs. Also considered are the effects of
      reductions in the number of entry-level positions for residency training and the
      changes in educational requirements for licensure on senior medical students.

PMID- 9580734
TI  - No to mandatory continuing medical education, yes to mandatory practice auditing
      and professional educational development.
AB  - The issue of mandatory continuing medical education (CME) is controversial.
      Traditional measures mandate only attendance, not learning, and have no
      measurable performance end points. There is no evidence that current approaches
      to CME, mandatory or voluntary, produce sustainable changes in physician
      practices or application of current knowledge. Ongoing educational development is
      an important value in a professional, and there is an ethical obligation to keep
      up to date. Mandating self-audit of the effect of individual learning on
      physician's practices and evaluation by the licensing authority are effective
      ways of ensuring the public are protected. The author recommends the use of a
      personal portfolio to document sources of learning, the effect of learning and
      the auditing of their applications on practice patterns and patient outcomes. A
      series of principles are proposed to govern its application.

PMID- 9580737
TI  - Campylobacter enteritis: it could happen to you!

PMID- 9580736
TI  - AIDS in Africa: a personal experience.

PMID- 9580738
TI  - Dictation software for MDs improving but frustration still part of the program.

PMID- 9580739
TI  - At least 12 US states refuse to recognize physician training accredited in
      Canada.
AB  - The easing of trade rules has done little to ease the movement of physicians
      between Canada and the US. Borders may be breaking down when it comes to the
      transfer of goods, Milan Korcok reports, but for physicians the moats in front of
      those borders appear to be getting deeper and more difficult to cross.

PMID- 9580740
TI  - Manitoba crash a wake-up call for "fly-in" physicians.
AB  - A December plane crash in northern Manitoba served to remind the province's "fly
      in" physicians of the perils their work may entail. Four people were killed and
      13 injured in the crash, which left Dr. Gerry Huot in serious condition in a
      Winnipeg hospital. The accident caused a serious head injury, and 4 months later
      he remains in hospital. It is causing some physicians to rethink their travel
      plans.

PMID- 9580741
TI  - Dr. Max King: the sad life and early death of Mackenzie King's physician brother.
AB  - While researching her best-selling biography, Mrs. King: The Life and Times of
      Isabel Mackenzie King, CMAJ contributing editor Charlotte Gray discovered a
      wealth of information about Dr. Dougal Macdougall (Max) King. Although he never
      became as famous as his older brother Mackenzie, Gray presents a convincing
      argument that Dr. Max King's life and early death speak volumes about medicine
      and the medical profession at the turn of the century. She also argues that
      Mackenzie King's own life would have been much different had his brother not died
      at the too young age of 42. Gray's book was nominated for the Viacom Award, which
      honours the best nonfiction book published annually in Canada.

PMID- 9580742
TI  - The Morrison ruling: the case may be closed but the issues it raised are not.

PMID- 9580743
TI  - Inflammatory bowel disease: short- and long-term treatments.

PMID- 9580744
TI  - Toremifene and letrozole for advanced breast cancer.

PMID- 9580745
TI  - Tiagabine for epilepsy.

PMID- 9580746
TI  - Surveillance for asthma--United States, 1960-1995.
AB  - PROBLEM/CONDITION: Asthma is one of the most common chronic diseases in the
      United States, and it has increased in importance during the preceding 20 years.
      Despite its importance, no comprehensive surveillance system has been established
      that measures asthma trends at the state or local level. REPORTING PERIOD: This
      report summarizes and reviews national data for specific end-points: self
      reported asthma prevalence (1980-1994), asthma office visits (1975-1995), asthma
      emergency room visits (1992-1995), asthma hospitalizations (1979-1994), and
      asthma deaths (1960-1995). DESCRIPTION OF SYSTEM: The National Center for Health
      Statistics (NCHS) annually conducts the National Health Interview Survey, which
      asks about self-reported asthma in a subset of the sample. NCHS collects
      physician office visit data with the National Ambulatory Medical Care Survey,
      emergency room visit data with the National Hospital Ambulatory Medical Care
      Survey, and hospitalization data with the National Hospital Discharge Survey.
      NCHS also collects mortality data annually from each state and produces
      computerized files from these data. We used these datasets to determine self
      reported asthma prevalence, asthma office visits, asthma emergency room visits,
      asthma hospitalizations, and asthma deaths nationwide and in four geographic
      regions of the United States (i.e., Northeast, Midwest, South, and West).
      RESULTS: We found an increase in self-reported asthma prevalence rates and asthma
      death rates in recent years both nationally and regionally. Asthma
      hospitalization rates have increased in some regions and decreased in others. At
      the state level, only death data are available for asthma; death rates varied
      substantially among states within the same region. INTERPRETATION: Both asthma
      prevalence rates and asthma death rates are increasing nationally. Available
      surveillance information are inadequate for fully assessing asthma trends at the
      state or local level. Implementation of better state and local surveillance can
      increase understanding of this disease and contribute to more effective treatment
      and prevention strategies.

PMID- 9580747
TI  - Making the diagnosis of cystic fibrosis.

PMID- 9580748
TI  - The hematopoietic garden: how does it grow?

PMID- 9580749
TI  - The consent form: a time for reassessment.

PMID- 9580750
TI  - Mediators of thyroid diseases in children.

PMID- 9580751
TI  - Identification of term infants at risk for neonatal morbidity.

PMID- 9580752
TI  - Congenital hypothyroidism and associated birth defects: implications for
      investigators and clinicians.

PMID- 9580753
TI  - Guidelines for antithrombotic therapy in pediatric patients.
AB  - Because of the relatively low incidence of TEs in children, the diagnostic and
      therapeutic approaches used are largely extrapolated from guidelines for adults.
      Features that differ in children compared with adults include underlying
      disorders, high incidence of CVL-related DVT in the upper venous system, and
      response to SH, warfarin, and thrombolytic agents. There is a paucity of
      information on the risk/benefit ratio of the therapeutic interventions and long
      term outcome. Clinical trials are urgently needed to clarify optimal management
      for pediatric patients with TEs.

PMID- 9580754
TI  - The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis
      Foundation Consensus Panel.
AB  - The diagnostic criteria proposed here are not likely to cover every possible
      clinical scenario, and there will be clinical dilemmas. For the vast majority of
      patients with CF, the diagnosis will be suggested by the presence of one or more
      characteristic clinical features, a history of CF in a sibling, or a positive
      newborn screening test result and will then be confirmed by laboratory evidence
      of CFTR dysfunction (Table V). Abnormal CFTR function will usually be documented
      by two elevated sweat chloride concentrations obtained on separate days or
      identification of two CF mutations. For patients in whom sweat chloride
      concentrations are normal or borderline and in whom two CF mutations are not
      identified, an abnormal nasal PD measurement recorded on 2 separate days can be
      used as evidence of CFTR dysfunction. Clinical judgment will continue to be
      essential in patients who have typical or "atypical" clinical features but who
      lack conclusive evidence of CFTR dysfunction. Such patients will require close
      clinical follow-up along with laboratory reevaluation as appropriate.

PMID- 9580755
TI  - Uncertainty in the diagnosis of cystic fibrosis: possible role of in vivo nasal
      potential difference measurements.
AB  - The diagnosis of cystic fibrosis (CF) is not always certain, despite extensive
      clinical evaluation, multiple sweat chloride tests, and genotype analysis. We
      hypothesized that nasal transepithelial potential difference measurements have a
      useful role in this situation. In 11 patients without an established diagnosis of
      CF, results of simultaneous nasal potential difference (PD) and sweat chloride
      measurements were compared with those from control subjects, obligate CF
      heterozygotes, and patients with a confirmed diagnosis of CF. Two patients
      conformed to the PD profile for CF patients, whereas nine had values
      corresponding to those of the healthy control subjects. Subsequently the 5
      thymidine (IVS8-5T) CF gene variant was identified in the two patients with
      abnormal PD measurements.

PMID- 9580756
TI  - Severe aplastic anemia of neonatal onset: a single-center retrospective study of
      six children.
AB  - We report severe aplastic anemia of neonatal onset diagnosed in six girls between
      1985 and 1995 in a single center. Initial blood cell counts (mean age 3.8 days
      old, 1 to 15 days) showed thrombocytopenia (six of six), anemia (four of six),
      and neutropenia (two of six). Neutrophil counts gradually decreased below 0.5 x
      10(9)/L, and severe aplastic anemia occurred in three patients by 3 months of age
      and in all patients by 1 year of age. Lymphocyte number and functions were
      normal. In all children bone marrow biopsy showed hypocellularity for age and
      absence of fibrosis, blasts, lymphocytic infiltrates, and cytologic
      abnormalities. Blood and medullary cytogenetic studies were normal. A search for
      known constitutional, viral, or toxic causes was negative. Immunosuppressive
      therapy failed to restore hematopoiesis (three of six). Five children received a
      bone marrow transplantation at an average age of 9 months (range 2.7 to 29
      months). One child is alive and well after a human leukocyte antigen-identical
      bone marrow transplantation, whereas the other four died. Both congenital onset
      and the high rate of familial involvement suggest that this condition may be
      inherited.

PMID- 9580757
TI  - Conventional consent with opting in versus simplified consent with opting out: an
      exploratory trial for studies that do not increase patient risk.
AB  - OBJECTIVE: The objective of this study was to assess a modified consent procedure
      allowed under federal regulations and developed for studies, particularly
      clinical trials, that are judged by the Institutional Review Board to reduce or
      have no effect on patient risk. STUDY DESIGN: This was a randomized trial of a
      conventional consent procedure that required parental signature to give consent
      (opting in) after a comprehensive disclosure of the rights of participants in
      research versus a modified consent procedure that required parental signature to
      refuse consent (opting out) after specific disclosures appropriate when risk is
      not increased. Consent was sought for a trial of primary follow-up care for
      disadvantaged infants at high risk, a trial judged by our Institutional Review
      Board to increase access to care for both groups. A blinded assessor interviewed
      mothers within 24 hours of the consent decision. RESULTS: Among the 44 mothers
      interviewed, the modified consent group scored higher than the conventional
      consent group in recall and understanding of study purpose and methods (47% vs
      30%; p < 0.02). Other comparisons provided no evidence that the modified consent
      procedure was less desirable. Virtually all mothers reported satisfaction.
      CONCLUSIONS: The modified approach may improve communication and facilitate
      studies judged by the Institutional Review Board to be risk-neutral or risk
      reducing. Further evaluation of a modified consent procedure for such studies is
      warranted.

PMID- 9580758
TI  - Bioassay of thyrotropin receptor antibodies with Chinese hamster ovary cells
      transfected with recombinant human thyrotropin receptor: clinical utility in
      children and adolescents with Graves disease.
AB  - OBJECTIVE: The objective of this study was to compare the clinical utility of a
      new bioassay for thyrotropin (TSH) receptor antibodies (Abs) with the
      conventional radioreceptor assay and with measurement of thyroid peroxidase Abs
      in the diagnosis of Graves disease in childhood. STUDY DESIGN: Serum samples
      obtained from 22 children and adolescents with Graves disease (19 hyperthyroid, 3
      in remission), 13 children and adolescents with chronic lymphocytic thyroiditis,
      and 17 normal children in a control group were evaluated. RESULTS: TSH receptor
      Abs were detected by bioassay in 10 (91%) of 11 patients with active Graves
      disease but in 0 of 2 patients in remission, 0 of 13 normal members of the
      control group, and 0 of 11 patients with chronic lymphocytic thyroiditis
      including 1 with thyrotoxicosis. The sensitivity and specificity of TSH receptor
      Abs detected by radioreceptor assay studied in the same 11 patients and in an
      additional 11 patients was similar to bioassay. In contrast, thyroid peroxidase
      Abs were detected in only 12 (71%) of 17 patients with Graves disease but in 11
      of 11 patients with chronic lymphocytic thyroiditis and in 0 of 17 members of the
      control group. CONCLUSION: Bioassay of TSH receptor Abs is both sensitive and
      specific for the diagnosis of active Graves disease in the young. When cost and
      simplicity are considered, however, bioassay offers no advantage over
      radioreceptor assay for initial diagnostic screening. Rather, bioassay for TSH
      receptor Abs may be useful in thyrotoxic patients who are negative initially in
      the radioreceptor assay or in treated patients whose clinical picture is
      discordant with results in the radioreceptor assay.

PMID- 9580759
TI  - Prospective validation of a scoring system for predicting neonatal morbidity
      after acute perinatal asphyxia.
AB  - OBJECTIVE: To prospectively validate a previously reported scoring system for
      identifying the near-term infant at risk for the multiple organ system sequelae
      of acute perinatal asphyxia. STUDY DESIGN: Prospective observational study.
      SETTING: Three Denver teaching hospitals, each providing comprehensive obstetric
      care. SUBJECTS: Newborn infants of 36 weeks or more gestation. INTERVENTION:
      None. STATISTICAL ANALYSIS: Chi-squared analysis with Fisher's exact test.
      OUTCOME: Scores consisting of graded abnormalities in fetal heart rate
      monitoring, umbilical arterial base deficit, and 5-minute Apgar score were
      calculated by the research nurse after admission of the infant to the nursery
      (range of possible scores, 0 to 9). A second nurse, blinded to these data,
      prospectively followed the newborn's hospital course for multiple organ system
      morbidity. RESULTS: Three thousand two hundred thirty-eight newborns were
      studied; 366 required neonatal intensive care unit admission. Eleven newborns had
      a score > or = 6 (mean umbilical artery pH = 6.98, base deficit = 17.1 mEq/L).
      Morbidities in these 11 newborns included seizures (2), hypoxic-ischemic
      encephalopathy (5), respiratory distress (9), hypotension (7), renal dysfunction
      (9), hypoglycemia/hypocalcemia (4), and thrombocytopenia or disseminated
      intravascular coagulopathy (3). The odds ratio (OR) and 95% confidence interval
      (CI) for newborns admitted to the neonatal intensive care unit with a score > or
      = 6 for having multiple organ system morbidity, defined as three or more affected
      organ systems, was 38.5 (95% CI, 9.2 to 127.8). The scoring system showed a
      stronger relationship with multiple organ system morbidity than did isolated
      individual indicators commonly used to identify asphyxia calculated on the same
      subjects: for those with pH < 7.00, OR 24 (95% CI, 6.4 to 94.1); base deficit >
      or = 10 mEq/L, OR 4.5 (95% CI, 1.9 to 10.3), and 5-minute Apgar score < or = 3,
      OR 7.4 (95% CI, 1.3 to 38.1). CONCLUSION: This scoring system, encompassing both
      immediate intrapartum and postpartum measures and acid-base status proximate to
      the time of delivery, is useful for rapidly identifying the term and near-term
      newborn at risk for multiple organ system morbidity after acute perinatal
      asphyxia.

PMID- 9580760
TI  - The effect of profound umbilical artery acidemia in term neonates admitted to a
      newborn nursery.
AB  - OBJECTIVE: To determine whether there were immediate adverse effects of an
      umbilical artery pH < or = 7.0 in term and near-term infants. STUDY DESIGN: All
      infants triaged to the newborn nursery with an umbilical artery pH < or = 7.0
      from May 1993 through April 1994 (n = 37) were prospectively identified; 35 of
      the 37 infants were enrolled and matched with nonacidemic control infants (n =
      35). Organ system dysfunction (neurologic, renal, hepatic, gastrointestinal) was
      evaluated either clinically or biochemically with selected blood and urine
      parameters. RESULTS: Acidemic and control groups were similar for pregnancy
      complications before labor, but acidemic infants were more often delivered by
      cesarean section (20/35 vs 6/35, p = 0.001). No differences existed between
      acidemic and control infants in gestational age, birth weight, neurologic
      evaluations, hearing deficits, feeding tolerance, and hepatic function. The
      acidemic group had a higher mean serum creatinine than control infants on day 2
      of life (0.90 +/- 0.34 vs 0.71 +/- 0.12 mg/dl, p = 0.005) and a greater number of
      infants with a urine Chemstrip positive for heme (14/35 vs 3/35, p = 0.005). No
      differences existed between groups in time to first void, urine specific gravity,
      and number of infants with microscopic hematuria. CONCLUSION: Term and near-term
      infants born with an umbilical artery pH < or = 7.0 and triaged to the newborn
      nursery on the basis of a stable appearance in the delivery room do not have
      clinical manifestations of hypoxia-ischemia in the 48 hours after birth. The
      higher mean serum creatinine for acidemic compared with control groups is
      presumably prerenal in origin and results from processes responsible for profound
      fetal acidemia. Infants with an umbilical artery pH < or = 7.0 and assessed to be
      clinically well can be treated similar to nonacidemic infants.

PMID- 9580761
TI  - Myocardial, erythropoietic, and metabolic adaptations to anemia of prematurity in
      infants with bronchopulmonary dysplasia.
AB  - OBJECTIVES: The effects of anemia of prematurity during bronchopulmonary
      dysplasia (BPD) as well as on the metabolic and erythropoietic functions were
      determined before and after a transfusion. Fourteen anemic (Hb range: 65-88
      gm/L), oxygen dependent (fraction of inspired oxygen < or = 35%), nonventilated,
      preterm infants with BPD were studied at a postnatal age of 6 +/- 2 weeks. STUDY
      DESIGN: Cardiac output, heart rate, mean velocity of circumferential fiber
      shortening, shortening fraction (SF), and stroke volume were assessed by pulsed
      and continuous wave Doppler echocardiography. Values for resting oxygen
      consumption, carbon dioxide production, and energy expenditure were obtained by
      indirect calorimetry. The affinity of oxygenated hemoglobin was determined by a
      blood oxygen dissociation analyzer. RESULTS: An increased hemoglobin level
      resulted in a suppression of erythropoietin secretion (p < 0.001), whereas heart
      rate, cardiac output, stroke volume, and SF decreased (p < 0.05). Weight gain
      before and after transfusion were similar. Plasma lactate levels decreased from
      1.6 +/- 0.3 to 1.2 +/- 0.3. Oxygen consumption, carbon dioxide production, and
      energy expenditure were not affected. CONCLUSIONS: Anemia of prematurity and BPD
      increase heart rate, cardiac output, stroke volume, and SF. These hemodynamic
      compensatory responses are normalized by transfusion.

PMID- 9580762
TI  - Prevention of iron-deficiency anemia: comparison of high- and low-iron formulas
      in term healthy infants after six months of life.
AB  - OBJECTIVES: For bottle-fed babies or nursing infants who receive milk
      supplements, the American Academy of Pediatrics recommends the use of iron
      fortified infant formula. Because these recommendations have not been universally
      adopted, the hematologic effects of currently available low-iron formulas need to
      be determined. STUDY DESIGN: Healthy Chilean 6-month-old infants (without iron
      deficiency anemia, born at term weighing > or 3.0 kg) who were totally or
      partially weaned from the breast were randomly allocated in a double-blind
      fashion to receive high-iron (n = 430) or low-iron formula (n = 405), containing
      an average of 12.7 mg/L or 2.3 mg/L, respectively, of elemental iron as ferrous
      sulfate. Iron status was determined at 12 months. RESULTS: The prevalence of iron
      deficiency anemia was not different in the high- and low-iron groups (2.8% versus
      3.8%, p = 0.35). Nevertheless, infants receiving high-iron formula had somewhat
      higher levels of hemoglobin and serum ferritin, greater mean cell volumes, and
      lower erythrocyte protoporphyrin levels (p < 0.005). CONCLUSIONS: Although high
      iron formulas are more efficacious in improving iron status, currently available
      low-iron formulas may prevent iron-deficiency anemia in selected healthy, term
      infant populations with otherwise poor sources of dietary iron after 6 months of
      life. Formulas with relatively small amounts of iron appear to prevent iron
      deficiency anemia. We speculate that the optimal level of iron fortification
      likely lies somewhere between the current levels in high- and low-iron formulas.

PMID- 9580763
TI  - Bone mineral content is not reduced despite low vitamin D status in breast milk
      fed infants versus cow's milk based formula-fed infants.
AB  - The effect of low or borderline vitamin D status on bone mineralization of
      exclusively breast milk-fed infants has not been studied. The low vitamin D
      status of Korean breast milk-fed infants may theoretically have adverse effects
      on bone mineralization. Assuming that bone mineral content (BMC) relates in part
      to vitamin D status, we hypothesized that serum 25-hydroxyvitamin D (25-OHD)
      concentration and BMC would be low, and serum osteocalcin concentration high,
      reflecting active bone turnover, in breast milk- versus formula-fed infants born
      in the winter. Eighteen breast milk- and 17 formula-fed infants were recruited at
      ages 2 to 5 months. The BMC of the lumbar1-4 spine region was measured by using
      dual energy x-ray absorptiometry. The BMC and serum osteocalcin levels were
      similar for both groups. The serum 25-OHD level was significantly lower in breast
      milk- than formula-fed infants; 44% of the breast milk group versus 6% of the
      formula group had serum 25-OHD levels less than 28 nmol/L (11 ng/ml), the lower
      limit of normal. The BMC did not correlate with the serum 25-OHD level. Thus BMC
      and serum osteocalcin levels in 2- to 5-month-old infants were not different by
      type of feeding, despite low vitamin D status in breast milk-fed infants. We
      speculate that adequate mineral absorption occurs during this period from a
      predominantly (vitamin D independent) passive transport mechanism.

PMID- 9580764
TI  - The effect of nursing on the brain activity of the newborn.
AB  - OBJECTIVE: To determine whether nursing influences brain activity in the newborn
      and whether there are differences in this respect between breast- or bottle
      feeding and pacifier sucking. STUDY DESIGN: Fifty unselected volunteer mothers
      and their healthy full-term infants, under care in the maternity ward after
      delivery, served as subjects. Thirty mother-infant pairs were studied in relation
      to breast-feeding and 20 to bottle-feeding and pacifier sucking. Breast-fed
      infants were studied between the 1st and 7th day after delivery (mean +/- 2.7
      days) and the infants in the bottle-fed group between the 1st and 8th day after
      delivery (mean +/- 3.3 days). METHODS: Qualitative and quantitative
      electroencephalogram (EEG), electrooculogram, submental electromyogram, and
      electrocardiogram were recorded before, during and after breast- and bottle
      feeding and pacifier sucking. RESULTS: The amplitude of the EEG increased
      significantly during breast-feeding in the posterior cortical areas in both
      hemispheres with a slight predominance on the right. Bottle-feeding caused a
      similar, but somewhat less marked change. When the breast- and bottle-fed infants
      were compared, a significant difference was found in only one parameter of the 84
      studied. Pacifier sucking had no significant effects on EEG activity. CONCLUSION:
      Nursing effects a change in the brain activity of the newborn. The cortical
      response to nursing is most probably a result of activation of the neurohumoral
      mechanisms related to hunger and satisfaction, including the hypothalamic,
      limbic, and other brain stem structures, which also regulate the sleep-wake cycle
      and modulate the level of cortical activity with respect to attention and
      vigilance.

PMID- 9580765
TI  - Intravenous correction of neonatal hypomagnesemia: effect on ionized magnesium.
AB  - OBJECTIVES: Neonatal hypomagnesemia is defined as total magnesium (TMg) < or =
      0.65 mmol/L (1.6 mg/dl). However, magnesium (Mg) deficiency and sufficiency
      overlap at serum values of 0.57 to 0.74 mmol/L (1.4 to 1.8 mg/dl). We
      hypothesized that (1) some infants with TMg < or = 0.65 mmol/L (1.6 mg/dl) have
      normal ionized Mg values (normal neonatal range 0.40 to 0.56 mmol/L (0.97 to 1.36
      mg/dl)); (2) the dose (6.0 mg of elemental Mg/kg) used to correct hypomagnesemia
      does not lead to elevation of ionized Mg; (3) after intravenous magnesium sulfate
      infusion, ionized calcium increases in patients with low baseline ionized Mg and
      decreases in patients with normal baseline ionized Mg. STUDY DESIGN: We recruited
      22 neonates with TMg < or = 1.6 mg/dl. They received intravenous sulfate (6 mg
      elemental Mg/kg) over a 1-hour period. Serum TMg, ionized Mg, and ionized Ca were
      measured before and after magnesium sulfate infusion. An ion-selective electrode
      was used to allow direct measurement of ionized Mg and ionized Ca. RESULTS:
      Thirteen (59%) of 22 neonates with TMg < or = 0.65 mmol/L (1.6 mg/dl) had normal
      IMg. In 7 (31%) of 22 cases ionized Mg increased slightly above 0.56 mmol/L (1.36
      mg/dl); the maximum value was 0.61 mmol/L (1.48 mg/dl). The change in ionized Ca
      concentrations and the baseline ionized Mg value were inversely correlated (r = 
      0.79; p < 0.0001). CONCLUSIONS: (1) Measurement of ionized Mg should prevent
      overdiagnosis and treatment of hypomagnesemia. (2) The dose used in this study is
      safe. (3) Ionized Mg concentrations are inversely correlated to the response of
      ionized Ca concentrations to an Mg load.

PMID- 9580766
TI  - Gilbert syndrome accelerates development of neonatal jaundice.
AB  - OBJECTIVE: Gilbert Syndrome (GS), associated with unconjugated hyperbilirubinemia
      and decreased bilirubin UDP-glucuronosyltransferase activity, is usually
      diagnosed after puberty. The role of GS in neonatal jaundice is unknown. This
      study tested the hypothesis that a recently identified molecular marker for GS (a
      TA insertion in the promoter of UGT1A, the gene encoding bilirubin UDP
      glucuronosyltransferase) is associated with neonatal jaundice. STUDY DESIGN:
      Transcutaneous jaundice index was measured shortly after birth and daily for the
      first week of life in 151 healthy infants. Genomic DNA was isolated from blood or
      buccal brushings, and the UGT1A promoter was amplified by the polymerase chain
      reaction to yield 90 (A[TA]6TAA, normal) or 92 (A[TA]7TAA, GS) base pair
      products. Statistical analysis used Kruskal-Wallis, Wilcoxon, and Fisher's exact
      tests. RESULTS: Nineteen (13%) subjects were homozygous for the A(TA)7TAA
      polymorphism associated with GS. The A(TA)7TAA homozygotes had a greater increase
      in jaundice index during the first 2 days of life than heterozygotes or A(TA)6TAA
      homozygotes. CONCLUSION: Although peak jaundice levels did not differ among
      groups, newborn infants with the molecular marker for GS have an accelerated
      increase in neonatal jaundice during the first 2 days of life.

PMID- 9580767
TI  - The development of low birth weight term infants and the effects of the
      environment in northeast Brazil.
AB  - OBJECTIVES: (1) To compare the mental and psychomotor development of low birth
      weight term (LBW-T) infants with that of appropriate birth weight (ABW) infants
      at 6 and 12 months of age. (2) To examine the relationship between developmental
      levels and social background. METHODS: A cohort of 131 LBW-T infants (1500 to
      2499 gm) and 131 ABW infants (3000 to 3499 gm) matched for sex and time of birth,
      recruited from six maternity centers in Northeast Brazil were followed for 1
      year. Their development was assessed with the Bayley Scales at 6 and 12 months of
      age, and at 12 months their behavior during the test was rated on five scales.
      Details of their families' socioeconomic status were recorded and the degree of
      stimulation in their homes was assessed. RESULTS: At 6 months of age the LBW-T
      infants had significantly lower scores than the ABW infants on the mental
      development index (MDI; 4.2 points lower, p < 0.001) and on the psychomotor
      development index (PDI; 7.3 points lower, p < 0.001). The difference had
      increased by 12 months of age (MDI 7.0 points lower, p < 0.001; PDI 9.9 points
      lower, p < 0.001). Socioeconomic variables were related to development at both
      ages in both groups. Maternal literacy was significantly related to the PDI in
      LBW-T infants at 12 months but not in ABW infants. Similarly, stimulation in the
      home was related to the MDI in LBW-T infants at 6 and 12 months but not in ABW
      infants. LBW-T infants were less active, cooperative, vocal, and happy, and were
      more inhibited than ABW infants. CONCLUSIONS: LBW-T infants had poorer
      development than ABW infants and differed in their behavior. There was an
      interaction between birth weight and the environment. LBW-T infants, but not ABW
      infants, were affected by the quality of stimulation in the home and maternal
      illiteracy.

PMID- 9580768
TI  - Sleep-disordered breathing in children with achondroplasia.
AB  - OBJECTIVE: Our objective was to characterize sleep-disordered breathing in 88
      children with achondroplasia aged 1 month to 12.6 years. RESULTS: At the time of
      their initial polysomnography, five children had previously undergone
      tracheostomy, and seven children required supplemental oxygen. Initial
      polysomnography demonstrated a median obstructive apnea index of 0 (range, 0 to
      19.2 apneas/hr). The median number of central apneas with desaturation per study
      was 0.5 (0 to 49), the median oxygen saturation nadir was 91% (50% to 99%), and
      the median peak end-tidal pCO2 was 47 mm Hg (36 to 87 mm Hg). Forty-two children
      (47.7%) had abnormal initial study results, usually caused by hypoxemia. Two
      children with severe obstructive sleep apnea eventually required continuous
      positive airway pressure therapy, and three additional children required
      tracheostomies. CONCLUSIONS: (1) Children with achondroplasia often have sleep
      related respiratory disturbances, primarily hypoxemia. (2) The majority do not
      have significant obstructive or central apnea; however, a substantial minority
      are severely affected. (3) Tonsillectomy and adenoidectomy decreases the degree
      of upper airway obstruction in most but not all children with achondroplasia and
      obstructive sleep apnea. (4) Restrictive lung disease can present at a young age
      in children with achondroplasia.

PMID- 9580769
TI  - Sleep-disordered breathing in children with myelomeningocele.
AB  - BACKGROUND: Although patients with myelomeningocele and the Chiari II
      malformation are known to have sleep apnea and respiratory control deficits, the
      prevalence, types, severities, and associations of sleep-disordered breathing
      (SDB) have not been adequately defined. METHODS: A cross-sectional study of our
      myelomeningocele clinic population was undertaken to correlate polysomnographic
      results with historical data and findings from magnetic resonance imaging of the
      Chiari malformation, pulmonary function results, and nocturnal pulse oximetry.
      RESULTS: A questionnaire survey of symptoms was available for 107 of 109 children
      (98% of the clinic population), and 83 patients agreed to undergo overnight
      polysomnography. Breathing during sleep was classified as normal in 31 cases
      (37%), mildly abnormal in 35 cases (42%), and moderately/severely abnormal in 17
      cases (20%). Among the 17 patients with moderately/severely abnormal SDB, 12
      patients had predominantly central apneas and 5 had predominantly obstructive
      apnea. Patients with a thoracic or thoracolumbar myelomeningocele, those who had
      previously had a posterior fossa decompression operation, those with more severe
      brain-stem malformations, and those with pulmonary function abnormalities were
      more likely to have moderately/severely abnormal SDB, relative risks (95%
      confidence intervals) 9.2 (2.9 to 29.3), 3.5 (1.3 to 8.9), 3.0 (0.9 to 10.5), and
      11.6 (1.6 to 81.3), respectively. Failure of obstructive SDB to resolve after
      adenotonsillectomy in four patients suggested abnormal control of pharyngeal
      airway patency during sleep. Nocturnal pulse oximetry accurately predicted
      moderately/severely abnormal SDB with a sensitivity of 100% and a specificity of
      67%. CONCLUSIONS: The pathogenesis of SDB in patients with myelomeningocele
      involves the functional level of the spinal lesions, congenital and acquired
      brainstem abnormalities, pulmonary function abnormalities, disorders of upper
      airway maintenance, and sleep state. Polysomnography and nocturnal pulse oximetry
      should be performed in high-risk patients to detect and classify SDB.

PMID- 9580770
TI  - Adenoid size is related to severity but not the number of episodes of obstructive
      apnea in children.
AB  - OBJECTIVE: The objective of this study was to determine the extent to which
      adenotonsillar hypertrophy contributes to the severity of obstructive sleep apnea
      (OSA) in children. STUDY DESIGN: Thirty-three consecutive children who were
      referred to a sleep disorders center for evaluation of suspected OSA had standard
      lateral neck roentgenography performed. Adenoid size was determined by measuring
      the adenoidal-nasopharyngeal (AN) ratio. Tonsil size was quantitated on physical
      examination. The severity of OSA was determined by full-night polysomnography in
      the sleep laboratory. RESULTS: All of the patients reported snoring with trouble
      breathing, apneas, or both problems witnessed by a parent. The patients'
      respiratory disturbance index ranged from 0 to 95.3 (mean +/- SD 12.5 +/- 9.1).
      The patients' AN ratio ranged from 0.48 to 0.98 (0.76 +/- 0.14); 30 (91%) of the
      33 patients had AN ratios greater than published normal means, and 16 (48%) had
      AN ratios more than 2 standard deviations above published means. Although the AN
      ratio and tonsil size did not predict the number of apneas, a significant
      relationship was seen between the AN ratio and the duration of obstructive apneas
      (r = 0.48, p < 0.01). Obesity (percent ideal body weight) was the only
      independent predictor for the number of respiratory events per hour of sleep (r =
      0.49, p < 0.01). Percent ideal body weight was also the major predictor of the
      lowest oxyhemoglobin saturation (r = -0.58, p < 0.0001), but the AN ratio also
      contributed to the variance in saturation, with a correlation coefficient (r) of
      0.69 for the two factors (p < 0.0001). CONCLUSION: Lymphoid hyperplasia affects
      the severity of apnea more than the number of obstructive apneas. The
      pathophysiologic characteristics of OSA in children probably involve complex
      interactions between pharyngeal size and mechanics.

PMID- 9580771
TI  - Prediction of adult hypertension by K4 and K5 diastolic blood pressure in
      children: the Bogalusa Heart Study.
AB  - OBJECTIVE: The objective of this study was to examine the reproducibility of K4
      and K5 diastolic blood pressure measurements and the ability to predict adulthood
      values. STUDY DESIGN: The Bogalusa Heart Study is a long-term epidemiologic study
      of cardiovascular disease risk factors from birth to early adulthood conducted in
      the biracial (one third black, two thirds white) community of Bogalusa,
      Louisiana. Analyses included blood pressure measurements taken on 12,139 subjects
      during multiple cross-sectional screenings from 1973 to 1994; 20% (N = 2530) had
      measurements taken as a child, ages 4 to 18 years, and during adulthood, ages 19
      to 32 years. Six resting blood pressure measurements were taken by trained
      observers with mercury sphygmomanometers at each screening with K1, K4, and K5
      recorded. Variance components analysis was used to evaluate the reliability of K4
      and K5. RESULTS: The total variance was larger for K5 (253 mm Hg2) than for K4
      (109 mm Hg2) at age 5 years. Variance for both K4 and K5 decreased with age. The
      interobserver variability was larger for K5 (more than 50% vs 40%). Childhood K4
      (vs childhood K5) was better correlated with adult K1 and K5 (0.28 vs 0.11 for
      K1; 0.33 vs 0.25 for K5 at age 11 to 13 years). K4 was also shown to have a
      higher odds ratio for predicting adult hypertension than K5 (1.57 vs 1.14 at age
      11 to 13 years). CONCLUSION: During childhood K4 is a more reliable measure of
      diastolic blood pressure than K5. K4 diastolic blood pressure measured in
      childhood is a better predictor of adult hypertension.

PMID- 9580772
TI  - Predictors of future ambulatory blood pressure in youth.
AB  - OBJECTIVE: The objective of this study was to determine the predictors of future
      ambulatory blood pressure in normotensive youths with family histories of
      essential hypertension. STUDY DESIGN: Eighty-eight healthy youths (mean age 10.9
      +/- 2.5 years; 52 blacks, 36 whites; 45 boys) were studied. During an initial
      visit anthropometric variables and hemodynamics were measured at rest and before,
      during, and after three laboratory stressors: postural change, forehead cold, and
      video game challenge. The subjects' ambulatory blood pressure was monitored for
      24 hours as part of a follow-up evaluation an average of 2.5 years later.
      RESULTS: Anthropometric and demographic variables and measures of reactivity to
      laboratory stressors were related to future daytime and nighttime ambulatory
      blood pressure. CONCLUSION: These findings provide important information on the
      predictors of ambulatory blood pressure and underscore the importance of resting
      blood pressure and adiposity. These results support the guidelines of the Second
      Task Force, which recommend the measurement of blood pressure and adiposity in
      the context of ongoing health care.

PMID- 9580773
TI  - Association of being overweight with greater asthma symptoms in inner city black
      and Hispanic children.
AB  - OBJECTIVE: To determine whether the weight status of inner city black and
      Hispanic children with asthma differs from that of their peers and to assess
      whether overweight asthmatic children experience greater asthma symptoms. STUDY
      DESIGN: A cross-sectional study in an ambulatory chest clinic of an inner city
      medical center. METHODS: We studied black and Hispanic children aged 2 to 18
      years (n = 209) with the single diagnosis of asthma. The peer control subjects
      consisted of a sample of black and Hispanic children aged 6 to 13 years (n =
      1017), enrolled in the New York City schools. Asthma symptoms, the number of
      asthma medications prescribed, and peak expiratory flow rate (PEFR) measurements
      were used to classify asthma severity and relate to body mass index (BMI).
      Bivariate categorical analysis and chi 2 tests were performed to examine the
      relationship between high BMI and the individual measures of asthma severity.
      RESULTS: The prevalence of overweight was significantly higher in children with
      moderate to severe asthma than in their peers. The risk of overweight based on a
      BMI in the 85th percentile or greater was significantly associated with the
      following measures of asthma severity: (1) the number of school days missed per
      year; (2) a PEFR less than or equal to 60% of the predicted PEFR; and (3) the
      number of asthma medications prescribed. CONCLUSIONS: The prevalence of
      overweight was significantly higher in children with moderate to severe asthma
      than in their peers, and being overweight was associated with significantly more
      severe asthma symptoms. Further studies in overweight asthmatic children are
      needed, including the effect of weight loss on lung function and other markers of
      asthma severity.

PMID- 9580774
TI  - Nitrofurantoin prophylaxis for bacteriuria and urinary tract infection in
      children with neurogenic bladder on intermittent catheterization.
AB  - OBJECTIVE: To determine the effect of nitrofurantoin prophylaxis on rates of
      bacteriuria and symptomatic urinary tract infection in children with chronic
      neurogenic bladder receiving clean intermittent catheterization. DESIGN: Double
      blind, placebo-controlled, crossover trial of 15 children receiving
      nitrofurantoin or placebo for 11 months (5 months receiving one drug, then 1
      month of washout followed by 5 months of the alternate drug). Weekly home visits
      were made. During each visit a sample of bladder urine was obtained by
      intermittent catheterization, signs and symptoms of urinary tract infection were
      recorded, and all medications were recorded as well as a capsule count of the
      study drug. RESULTS: During nitrofurantoin the frequency of bacteriuria remained
      high. Cultures of 74% (203 of 274) of the 274 samples on placebo were positive
      for a pathogen (> or = 10(4) colony-forming units per milliliter) compared with
      65% (165 of 252) of the 252 samples on nitrofurantoin. The bacterial species
      responsible for bacteriuria, however, were altered; Escherichia coli, the most
      common pathogen isolated during placebo, was replaced by resistant Klebsiella
      spp. and Pseudomonas spp. during nitrofurantoin. The carriage of these resistant
      organisms tripled during nitrofurantoin. Symptomatic infection dropped in half on
      nitrofurantoin, but this decline was due solely to infections caused by E. coli.
      Despite an increased frequency of resistant organisms on nitrofurantoin
      prophylaxis, an increase in urinary tract infections caused by these resistant
      organisms did not occur. CONCLUSION: Routine use of nitrofurantoin prophylaxis in
      an attempt to eradicate bacteriuria in patients with chronic neurogenic bladder
      is not effective.

PMID- 9580775
TI  - Long-term use of high-dose benzoate and dextromethorphan for the treatment of
      nonketotic hyperglycinemia.
AB  - OBJECTIVE: The objective of this study was to test the hypotheses that reduction
      of glycine and blocking of the N-methyl-D-aspartate receptor channel complex
      would be beneficial for both seizure reduction and developmental progress in
      patients with nonketotic hyperglycinemia. METHODS: We administered benzoate (at
      doses of 500 to 750 mg/kg/day) and dextromethorphan (at doses of 3.5 to 22.5
      mg/kg/day) to four infants with nonketotic hyperglycinemia with follow-up of 3
      months to 6 years. RESULTS: Benzoate reduced to normal the glycine concentration
      in plasma and substantially reduced but did not normalize the glycine
      concentration in cerebrospinal fluid. Dextromethorphan was a potent
      anticonvulsant in some but not all patients. There was remarkable interpatient
      variability in dextromethorphan metabolism. Three patients are living (ages
      ranging from 4 to 6 years) and are moderately to severely developmentally
      delayed; two are free of seizures. The third patient, with the slowest
      development, had intractable seizures for nearly a month before diagnosis, and
      although seizure-free for 30 months, now has grand-mal seizures. One patient died
      of intractable seizures at 3 months. CONCLUSIONS: These outcomes suggest that
      benzoate and dextromethorphan are not uniformly effective in nonketotic
      hyperglycinemia, but for some patients they improve arousal, decrease or
      eliminate seizures, and allow for some developmental progress. Trials with
      additional patients and other receptor channel blockers are warranted.

PMID- 9580776
TI  - Identification of a genetic cause for isolated unilateral coronal synostosis: a
      unique mutation in the fibroblast growth factor receptor 3.
AB  - To determine whether the autosomal dominant fibroblast growth factor receptor 3
      (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either
      apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior
      plagiocephaly (N = 10) were studied for this mutation. Of 37 patients with
      unicoronal synostosis, 4 tested positive for the Pro250Arg mutation in FGFR3, and
      33 were negative for this mutation. In three mutation positive patients with full
      parental studies, a parent with an extremely mild phenotype was found to carry
      the same mutation. None of the 6 patients with nonsynostotic plagiocephaly and
      none of the 4 patients with additional suture synostosis had the FGFR3 mutation.
      Because it is impossible to predict the FGFR3 Pro250Arg mutation status based on
      clinical examination alone, all patients with unicoronal synostosis should be
      tested for it. To assess their recurrence risk, all parents of mutation positive
      patients should be tested regardless of their clinical findings, because the
      phenotype can be extremely variable and without craniosynostosis.

PMID- 9580777
TI  - Clinical and molecular heterogeneity in carbonic anhydrase II deficiency and
      prenatal diagnosis in an Italian family.
AB  - Carbonic anhydrase (CA) II deficiency is characterized by osteopetrosis, renal
      tubular acidosis, cerebral calcification, and usually severe mental retardation.
      We describe an Italian boy with this disease whose mental retardation was
      relatively mild and whose renal tubular acidosis had only a distal component. A
      novel mutation of a gt-->tt change of splice donor site at the 5' end of intron 6
      was demonstrated. Comparison of this patient with two previous Italian families
      with different mutations illustrates the clinical and molecular heterogeneity of
      this disease. The identification of the mutation in this family provided the
      opportunity for prenatal diagnosis in a subsequent pregnancy.

PMID- 9580778
TI  - Clinical features of Behcet's disease in children: an international collaborative
      study of 86 cases.
AB  - OBJECTIVES: The objective of this study was to characterize the clinical picture
      of Behcet's disease (BD) in children. STUDY DESIGN: A questionnaire was completed
      by five BD specialists from Turkey, France, Iran, or Saudi Arabia. We first
      reviewed 86 cases retrospectively with a specially designed computerized database
      and then selected 65 who met the criteria of the International Study Group for
      BD, which include buccal aphthosis plus at least two among recurrent genital
      aphthosis, eye lesions, skin lesions, and positive pathergy test. The remaining
      21 patients, who had features suggestive of BD but did not fulfill the
      international criteria, were analyzed separately and then compared with the other
      65 patients. RESULTS: BD affected boys and girls equally. The clinical picture
      frequently included mucocutaneous lesions. Uveitis was less frequent than in
      adults but carried a poor prognosis, especially in male patients (p < 0.001). The
      mortality rate (3%) was related to large vessel involvement. Familial cases were
      particularly frequent (15%). Erythema nodosum and skin hypersensitivity were
      common in Turkish patients, whereas neuro-BD was more frequent in French and
      Saudi Arabian patients. Patients who did not fulfill the international criteria
      had significantly less genital aphthosis (p < 0.01), less skin lesions or
      hypersensitivity (p < 0.01), and less uveitis (p < 0.01). CONCLUSION: BD in
      children is similar to BD in adults. The high frequency of familial cases calls
      for further investigation of the immunogenetic factors that may favor early
      expression of the disease.

PMID- 9580779
TI  - Increased incidence of congenital malformations in children with transient
      thyroid-stimulating hormone elevation on neonatal screening.
AB  - We investigated the incidence of congenital malformation in all infants with
      raised thyroid-stimulating hormone (TSH) levels on neonatal screening in Scotland
      between August 1979 and December 1993. Of 344 infants with elevated TSH, 31 (9%)
      had one or more malformations: 12 cardiac 15 noncardiac, and 16 dysmorphic
      syndromes (including 5 with Down syndrome). Criteria were devised to distinguish
      between definite or probable congenital hypothyroidism and transient TSH
      elevation. Congenital hypothyroidism was considered definite in 224 (65.1%)
      infants and probable in 11 (3.2%). Eighty-eight (25.6%) infants had transient TSH
      elevation, whereas thyroid status was uncertain in 21 (6.1%). In the definite
      group 12 (5.4%) infants had one or more malformations compared with 13 (14.8%) in
      the transient group. Cardiac malformation, noncardiac malformation, dysmorphic
      syndromes, and "sickness" were much more frequent in the transient compared with
      the definite group: 5.7% versus 1.8%, 8.0% versus 1.8%, 6.8% versus 2.7%, and
      37.5% versus 7.1%, respectively. The incidence of congenital malformation in
      bonafide congenital hypothyroidism is lower than has been previously reported.
      The high incidence of congenital malformation associated with transient TSH
      elevation indicates the need to reevaluate the diagnosis of hypothyroidism in all
      infants with TSH elevation and concurrent illness or malformation.

PMID- 9580780
TI  - The effect of inhaled nitric oxide therapy on bleeding time and platelet
      aggregation in neonates.
AB  - The effect of inhaled nitric oxide (iNO) on bleeding time and platelet
      aggregation was studied in nine newborn infants with resolving pulmonary
      hypertension. Infants treated with iNO at 40 ppm for 30 minutes had bleeding
      times that were nearly twofold longer than those obtained 24 hours after iNO was
      discontinued. iNO had no effect on in vitro platelet aggregation studies.

PMID- 9580781
TI  - Juvenile multiple sclerosis: clinical features and prognostic characteristics.
AB  - In a retrospective study we analyzed clinical features and their prognostic
      significance in 72 patients with onset of multiple sclerosis by the age of 21
      years. In juvenile multiple sclerosis disease progression does not depend on age
      of onset, severity of neurologic involvement, or polysymptomatic or
      monosymptomatic involvement at presentation.

PMID- 9580782
TI  - Is Down syndrome a risk factor for poor outcome after repair of congenital heart
      defects?
AB  - Down syndrome is commonly associated with significant congenital heart disease
      with the potential for early development of pulmonary hypertension. As such,
      children with Down syndrome may be at increased risk for both perioperative and
      long-term mortality. The purpose of this study, using data collected from a
      population-based outcomes study, is to analyze the potential role that Down
      syndrome plays in the outcome of surgically "corrected" congenital heart disease.
      Data were collected from a registry of all Oregon residents who, in the period
      1958 to the present, had a reparative operation for one of 14 congenital cardiac
      malformations when younger than 18 years (N = 3965 patients). Down syndrome was
      present in 289 (7%) of the total registry patients. In evaluating the cardiac
      mortality associated with Down syndrome for each of the repaired cardiac
      malformations, only complete atrioventricular septal defect was associated with
      significantly higher perioperative (13% vs 5%) as well as higher overall late
      cardiac mortality through 20 years after the operation (20% vs 5%; p = 0.04). The
      survival outcomes for each of the other cardiac malformations were similar for
      children with and without Down syndrome.

PMID- 9580783
TI  - Chronic neurologic disease with visual, gait, and bladder problems in a male
      teenager.

PMID- 9580784
TI  - Testing for hearing loss after meningitis.

PMID- 9580785
TI  - Compartment syndrome and Varicella.

PMID- 9580786
TI  - Hepatoblastoma and birth weight.

PMID- 9580787
TI  - Pigmented viral warts: a clinical and histopathological study including human
      papillomavirus typing.
AB  - Although clinical, histological and viral correlations have recently been
      established among pigmented warts, homogeneous intracytoplasmic inclusion bodies
      and related types of human papillomavirus (HPV) (HPV 65, 4 and 60), the causes of
      the pigmentation remain unknown. In this study, comparative histological and
      histochemical analyses were performed with 53 pigmented (34 HPV 65-induced, 12
      HPV 4-induced and seven HPV 60-induced) and 73 non-pigmented warts (27 HPV 2
      induced, 23 HPV 1-induced, 12 HPV 63-induced, six unknown HPV-type induced and
      five HPV 60 induced) to clarify the causes of the pigmentation. Electron
      microscopy was also used to examine the pigmented warts. Many melanin blockade
      melanocytes were identified in all of the pigmented warts with Masson-Fontana
      staining and electron microscopy, and increased melanin in keratinocytes was also
      noted in 22 pigmented warts, suggesting that the dispersion of melanin granules
      in the dendrites of the melanin blockade melanocytes and the increased melanin
      granules in keratinocytes are the primary contributors to the pigmentation of the
      warts. The homogeneous intracytoplasmic inclusion bodies might also play a part
      in the darkening of the warts, as only the cases which had the inclusion bodies
      as well as the melanin blockade melanocytes were clinically pigmented. Although
      melanin blockade melanocytes were seen in a few cases of HPV 1- and HPV 2-induced
      warts in which the homogeneous inclusion bodies were not observed, the warts were
      not clinically pigmented. Melanin blockade melanocytes were not seen in any of
      the HPV 63-induced non-pigmented warts. In conclusion, the pigmented warts were
      associated with one of the related types of HPV (HPV 65, 4 and 60), and the
      pigmentation of the lesions is thus thought to be caused primarily by melanin
      blockade melanocytes. The homogeneous intracytoplasmic inclusion bodies might
      also play a part in the darkening of the lesions. This is the first report
      dealing with the pigmentary disorder associated with specific types of HPV.

PMID- 9580788
TI  - Palmoplantar pustulosis: a clinical and immunohistological study.
AB  - Pustulosis palmoplantaris (PPP) is a common chronic skin disease, which is very
      resistant to treatment. It is not known why the lesions are located in the palms
      and soles. There are few studies of the disease and in particular studies of the
      histology. Fifty-nine patients with PPP answered a questionnaire concerning their
      medical history and 39 of them were clinically examined. Biopsy specimens were
      taken from involved skin in 22 of the 39 patients and studied
      immunohistologically for tryptase+ mast cells, EG2+ eosinophils, lipocalin+
      neutrophils and CD3+ T lymphocytes. The sweat gland and sweat duct were
      visualized with AE1/AE3 antibody (cytokeratins 1-8, 10, 14/15, 16, 19). In
      addition to neutrophils in the pustule and lymphocytes in the upper dermis, there
      were also large numbers of mast cells and eosinophils in the subpustular area.
      Numerous eosinophils were present in the pustule. The epidermal part of the
      eccrine duct was not detectable in any of the specimens from patients with PPP
      but was present in all of the nine control persons (including two smokers). The
      results indicate that the acrosyringium is involved in the inflammation and also
      that mast cells and eosinophils participate in a hitherto unknown way. Of the 39
      patients clinically examined, two had previously diagnosed thyroid disease and
      two had gluten hypersensitivity. Seventeen had one or several abnormal serum
      concentrations of thyroid-stimulating hormone, thyroxin, antibodies against
      thyroglobulin or thyroperoxidase and 10 had immunoglobulin (Ig) A antibodies to
      gliadin. The mean +/- SD for serum IgA and for eosinophil cationic protein was
      increased. From the questionnaire the most notable finding was that 56 of the 59
      patients had been or still were smokers, all of whom had started smoking before
      the first signs of PPP. We hypothesize that the acrosyringium might be the target
      for the inflammation and that PPP is linked to autoimmune thyroid disease and
      smoking.

PMID- 9580789
TI  - Dermal mast cells in scleroderma: their skin density, tryptase/chymase phenotypes
      and degranulation.
AB  - To determine the distribution, tryptase/chymase phenotypes and degranulation of
      mast cells (MCs) in the dermis of patients with scleroderma, we examined MC
      density in the skin of 22 patients with systemic sclerosis (SSc) and 11 with
      localized scleroderma (LSc). We used antitryptase and antichymase antibodies
      after Carnoy's fixation. Detailed reports of two representative patients with SSc
      and LSc are included. In the scleroedematous stage (grade 1) showing oedema in
      both papillary and reticular dermis with variable homogenization of collagen
      bundles in the reticular dermis, MC skin density was variable in each specimen
      although MC skin density, as a whole, was significantly increased as compared
      with normal skin (P < 0.05). In the sclerotic stage (grade 2) characterized by
      homogenization of collagen bundles in the entire dermis, MC skin density was
      significantly decreased as compared with normal skin (P < 0.005). LSc showed
      changes similar to those in SSc. The ratio of MCTC cells (both tryptase- and
      chymase-positive MC) to MCT cells (tryptase-positive but chymase-negative MC) was
      variable in SSc and LSc. MCT cells were exclusively dominant in three patients
      with SSc and two with LSc. In a patient with SSc (patient 1) showing remarkable
      perivascular and interstitial oedema in the upper dermis, MC skin density was
      increased in the oedematous portion and tryptase-positive granules were
      distributed in extracellular locations. In another patient with LSc (patient 2),
      tryptase positivity increased and chymase positivity decreased in both number and
      intensity as the skin sclerosis progressed. MCs must have variable interactions
      with the lesional skin in SSc and LSc. The present study suggests that MCs are
      involved in the development of interstitial oedema.

PMID- 9580790
TI  - Minoxidil upregulates the expression of vascular endothelial growth factor in
      human hair dermal papilla cells.
AB  - The hair follicle dermal papilla which controls hair growth, is characterized in
      the anagen phase by a highly developed vascular network. We have demonstrated in
      a previous study that the expression of an angiogenic growth factor called
      vascular endothelial growth factor (VEGF) mRNA varied during the hair cycle. VEGF
      mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase, but
      during the catagen and telogen phases. VEGF mRNA is less strongly expressed. This
      involvement of VEGF during the hair cycle allowed us to determine whether VEGF
      mRNA expression by DPC was regulated by minoxidil. In addition, the effect of
      minoxidil on VEGF protein synthesis in both cell extracts and DPC-conditioned
      medium, was investigated immunoenzymatically. Both VEGF mRNA and protein were
      significantly elevated in treated DPC compared with controls. DPC incubated with
      increasing minoxidil concentrations (0.2, 2, 6, 12 and 24 mumol/L) induced a dose
      dependent expression of VEGF mRNA. Quantification of transcripts showed that DPC
      stimulated with 24 mumol/L minoxidil express six times more VEGF mRNA than
      controls. Similarly, VEGF protein production increases in cell extracts and
      conditioned media following minoxidil stimulation. These studies strongly support
      the likely involvement of minoxidil in the development of dermal papilla
      vascularization via a stimulation of VEGF expression, and support the hypothesis
      that minoxidil has a physiological role in maintaining a good vascularization of
      hair follicles in androgenetic alopecia.

PMID- 9580791
TI  - Melanoma excision by general practitioners in north-east Thames region, England.
AB  - A retrospective study of pathology reports of melanomas excised by general
      practitioners (GPs) was undertaken in the course of a population-based study of
      melanoma, with a telephone survey of the current practice of those GPs who had
      excised melanomas. The objectives of this study were to identify all cases of
      cutaneous melanoma excised by GPs in the North-East Thames Region between 1989
      and 1993, and to review the management of those patients. The main outcome
      measures of the study were: (i) the patterns of distribution of GP excisions
      within the region; (ii) the histological subtypes of melanomas excised, the
      accuracy of the pre-excision clinical diagnosis and the adequacy of treatment of
      the GP-treated tumours compared with the control group; and (iii) the reported
      current practice in the management of pigmented skin lesions by the GPs who had
      excised melanomas. Eight hundred and nineteen melanomas were excised in the
      region during the study period, of which 59 were excised by GPs. The Breslow
      thickness of tumours was similar in both GP-excised and non-GP-excised groups.
      Tumours were more likely to be amelanotic in the GP-excised group (P < 0.001).
      Incomplete excision was significantly more likely in the GP group (P < 0.001).
      The GPs made a confident clinical diagnosis of melanoma in only 17% of patients
      prior to surgery. The reported referral rate to specialists by this subset of GPs
      of patients with pigmented lesions was low, and at interview half of the GPs
      reported that they felt confident enough to manage patients with suspected skin
      cancers on their own. The majority of the GPs did not routinely obtain
      histological examination of skin lesions they believed to be benign. In
      conclusion, there are problems with the accuracy of clinical diagnosis and
      inadequacy of excision of melanomas removed in primary care. In the majority of
      cases, however, patients were subsequently appropriately treated by referral to
      specialist units. There was an under-usage of pathological examination of samples
      by the GPs interviewed.

PMID- 9580792
TI  - The effect of the introduction of a pigmented lesion clinic on the interval
      between referral by family practitioner and attendance at hospital.
AB  - The value of pigmented lesion clinics (PLCs) for the early detection and
      treatment of malignant melanoma has been questioned. We have examined the effect
      of the introduction of a PLC on the referral interval between patients with
      melanoma presenting to their general practitioner (GP) and their attendance at
      hospital. The case notes of all patients presenting with melanoma in
      Leicestershire between 1984 and 1994 were reviewed. There was a significant
      initial reduction in the mean referral interval following the introduction of the
      PLC from 27.9 days (SEM = 6.6) in 1984 to 11.3 (2.3) days in 1987 (P < 0.01).
      However, the referral interval gradually rose over the following 7 years to a
      mean of 20.4 (4.4) days in 1994, which was not significantly better than the
      1985/86 level. The increase in the referral interval was due to a greater
      percentage of melanomas being referred to clinics other than the PLC. Only 48% of
      melanomas were referred to the PLC in 1994 compared with 70% in 1987. We also
      reviewed the referral letters for those patients presenting in 1991 and 1994, and
      decided, on the basis of the content of the letter, whether the GP had suspected
      the diagnosis of melanoma. More than 50% of the melanomas were correctly
      diagnosed by the GP, but only half of these were then appropriately referred to
      the PLC. We believe that PLCs are of value in the early diagnosis and treatment
      of melanoma, but only if they are appropriately utilized by GPs.

PMID- 9580793
TI  - Sun exposure and large numbers of common and atypical melanocytic naevi: an
      analytical study in a southern European population.
AB  - The study analysed the relationship between high counts of common naevi and
      numbers of atypical naevi (AN) in sites differing in exposure to the sun. A
      series of 90 subjects with 100 or more common naevi (cases) and 92 controls was
      investigated by means of a case-control study. A striking association between
      high numbers of common naevi and prevalence of AN (whole body) was found. The
      adjustment for phenotype and phototype did not obscure this association. Similar
      findings were obtained after exclusion of subjects with familiarity for melanoma.
      Cases had more AN than controls in all the body sites, except for the buttocks,
      where sun exposure can be considered minimal or absent: in this site, an excess
      of common naevi but not of AN was found. The present study suggests that subjects
      with high common naevi counts show a higher prevalence of AN independently of
      their complexion, sunburn history and family history of melanoma. Phenotypic
      expression of AN seems to be enhanced by direct sun exposure.

PMID- 9580794
TI  - Clinical and prognostic relevance of serum S-100 beta protein in malignant
      melanoma.
AB  - To assess the clinical and prognostic relevance of serum S-100 beta in malignant
      melanoma serum levels of S-100 beta protein were measured in 84 patients with
      malignant melanoma. Using a cut-off value of 0.3 microgram/L the sensitivity was
      0% (none of 36) in patients with stage II, 31% (four of 13) in patients with
      stage III and 69% (24 of 35) in patients with stage IV. In the reference group
      serum S-100 beta was below 0.3 microgram/L in all cases (specificity = 100%). A
      significant correlation existed between serum S-100 beta values and clinical
      staging as well as survival. In patients with distant metastases the serum
      concentration of S-100 beta protein correlated well with the number of affected
      organs. Serial measurement in these patients revealed that tumour progression was
      accompanied by rising S-100 beta values whereas declining values could only be
      revealed in one patient with a dramatic clinical response to therapy. Our results
      suggest that serum S-100 beta determination is a useful marker for the evaluation
      of prognosis in patients with metastatic malignant melanoma and should be
      included in the clinical staging.

PMID- 9580795
TI  - Soluble E-selectin, other markers of inflammation and disease severity in
      children with atopic dermatitis.
AB  - E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular
      cell adhesion molecule-1 (VCAM-1) are membrane-bound adhesion molecules which
      mediate the attachment of leucocytes to endothelial cells. These molecules are
      preferentially expressed on activated endothelium. The soluble forms of these
      molecules (sE-selectin, sP-selectin, sICAM-1 and sVCAM-1) are present in the
      circulation as a result of shedding. Some of the soluble adhesion molecules have
      been thought to reflect disease activity in atopic dermatitis (AD). To evaluate
      their potential to reflect disease activity in AD, we correlated their plasma
      concentration with clinical severity measured by objective SCORAD (SCORing Atopic
      Dermatitis). Furthermore, levels of total IgE, specific IgE, and eosinophil
      cationic protein (ECP) were determined. SCORAD and sE-selectin levels were
      significantly increased in children with specific IgE for both food and
      inhalation allergens (P < 0.05). ECP consistently showed an increase with the
      scores of SCORAD, but no statistical significance was reached. Disease activity
      was significantly correlated with the plasma levels of sE-selectin (rs = 0.6, P <
      0.0005) but not with sP-selectin, sICAM-1 and sVCAM-1. This agrees with recent
      studies performed in adults with AD, and supports the potential of sE-selection
      as a parameter for monitoring disease activity in young children with AD.

PMID- 9580796
TI  - Community validation of the United Kingdom diagnostic criteria for atopic
      dermatitis in Romanian schoolchildren.
AB  - Although the U.K. modification of Hanifin and Rajka's diagnostic criteria for
      atopic dermatitis (AD) for use in epidemiological studies has demonstrated good
      validity and repeatability when previously tested in a U.K. community setting,
      little is known about its performance in other countries where different
      cultural, educational and linguistic factors could impair validity. We used a
      questionnaire to test the validity of the U.K. criteria as a point prevalence
      measure of AD in 1114 Romanian schoolchildren aged 6-12 years against the
      clinical diagnosis of a dermatologist with an interest in AD, who was unaware of
      the questionnaire content and responses. The sensitivity and specificity of the
      U.K. criteria for AD in this setting was 74% and 99%, respectively, an
      improvement rather than a deterioration in validity when compared with the
      previous U.K. study. Test-retest repeatability for all of the questions
      pertaining to the U.K. criteria using the chance-corrected kappa statistic was
      high, with values of 0.72 and over. The positive predictive value of the criteria
      was lower than in the U.K. study (63% compared with 80%, respectively) due to the
      very low prevalence of AD in this study (2.4%). The validity of a parental report
      of 'eczema' was poor, with a sensitivity of 22%, specificity of 97% and positive
      predictive value of 18%. This study suggests that the U.K. criteria perform well
      in settings outside the U.K., although care has to be taken when using the
      criteria to ascertain cases in settings where the prevalence of AD is very low.

PMID- 9580797
TI  - Renal function after 10 years' treatment with cyclosporin for psoriasis.
AB  - Renal function was assessed by measuring serum creatinine and glomerular
      filtration rate (GFR) in two groups of patients with chronic plaque psoriasis who
      had been treated with cyclosporin A (CyA), average dose 2.8 mg/kg per day (range
      1-5 mg/kg per day). Group I was our original cohort of nine patients, seven of
      whom had received CyA for an average period of 10 years (range 9.5-11 years).
      These seven patients showed a persistent increase in serum creatinine > 30% from
      baseline measurement and four of the seven had persistent increases > 50%. The
      GFR, which was first measured after 2.5 years of treatment, showed at 10 years a
      decrease of > 30% in two patients and of > 50% in one patient. Three of the seven
      showed stable renal function while two had repeat renal biopsy because of
      deteriorating renal function and histology showed further evidence of CyA
      nephrotoxicity compared with that after 5 years' treatment. Two of the nine
      patients in group I had discontinued CyA 5 years previously after 5 years of
      treatment because of CyA nephrotoxicity on renal biopsy and impaired renal
      function. This impairment of renal function showed improvement during the 5 years
      of follow-up, implying reversibility of CyA nephrotoxicity. The second group of
      20 patients had received CyA for an average duration of 6 years (range 5-8
      years). Nine of the 20 patients showed persistent increases in serum creatinine
      of > 30% from baseline and five showed persistent increases of > 50%. The GFR
      showed a persistent decrease of > 30% in seven patients and of > 50% in two
      patients. This study has shown that nephrotoxicity is associated with long-term
      treatment with CyA. However, there is patient variation as to when nephrotoxicity
      commences and its speed of progression. On discontinuing CyA the impairment of
      renal function improves with time. Providing renal function is monitored with GFR
      and renal biopsy in addition to serum creatinine then long-term (5-10 years) CyA
      treatment can be justified in severe psoriasis not responsive to other
      treatments.

PMID- 9580798
TI  - The prescription of isotretinoin to women: is every precaution taken?
AB  - A questionnaire survey of dermatologists practising in Scotland was carried out
      to assess strategies for the management of women prescribed isotretinoin for
      acne. The results of the study suggested that the prevention of pregnancy during
      treatment is of considerable concern to dermatologists: over 90% routinely asked
      women about sexual activity and 97% routinely gave both verbal and written advice
      on the need to avoid pregnancy during treatment. However, clinical practices
      which might place women at risk of pregnancy were identified: only 30% of
      trainees and 51% of consultants routinely carried out pregnancy tests before
      treatment, and when tests were carried out, there was a tendency to rely on
      potentially insensitive urine assays. Additionally, there was an apparent lack of
      recognition of the possibility of sexual activity in girls aged under 16 years.
      Suggestions for the management of women prescribed isotretinoin include taking a
      sexual history from all women; providing clear information on the need to avoid
      pregnancy during treatment; obtaining informed consent prior to treatment;
      recommending the use of effective contraceptive measures; and exclusion of
      pregnancy prior to treatment by means of a suitably timed blood or urine sample
      and sensitive assay technique.

PMID- 9580799
TI  - Treatment of psoriasis with fumaric acid esters: results of a prospective
      multicentre study. German Multicentre Study.
AB  - Systemic treatment of psoriasis with fumaric acid esters (FAE) has been found
      effective by empirical means. In recent years clinical studies have confirmed the
      antipsoriatic activity of a defined mixture of different FAE. The aim of the
      present prospective multicentre study was to investigate further the efficacy and
      safety of FAE therapy in a large number of patients with severe psoriasis
      vulgaris. From 101 patients included in the study 70 completed the treatment
      period of 4 months. Discontinuation was due to adverse events in seven, lack of
      efficacy in two, and other reasons, such as non-attendance for scheduled visits,
      in 22 patients. Evaluation of overall efficacy showed a decrease in psoriasis
      area and severity index of 80% after 4 months of FAE therapy. Laboratory
      investigations revealed a slight overall decrease of lymphocytes during the
      treatment period which was more than 50% below baseline in 10 patients. During
      weeks 4 and 8 mean eosinophil counts were above the normal range. At the end of
      FAE therapy elevated eosinophil counts had returned to normal values. None of the
      patients showed changes in renal function parameters throughout the study.
      Adverse events were reported in 69% of the patients mainly consisting of
      gastrointestinal complaints (56%) and flushing (31%). In five patients
      gastrointestinal complaints and in two patients flushing led to withdrawal from
      the study. Taken together the results of this multicentre study showed in a large
      number of patients that systemic FAE treatment is effective in severe psoriasis
      vulgaris. Transient eosinophilia seems to be a characteristic feature of FAE
      therapy, while lymphocytopenia is usually mild. Adverse effects are dose-related
      and consist mainly of gastrointestinal complaints and flushing.

PMID- 9580800
TI  - Demodex folliculorum and topical treatment: acaricidal action evaluated by
      standardized skin surface biopsy.
AB  - A standardized skin surface biopsy was performed in 34 patients suffering from
      skin diseases with high Demodex folliculorum density (Dd) > 5D/cm2 before, during
      and after topical treatment. The patients were randomized into six comparable
      groups to study six topical treatments: metronidazole 2%, permethrin 1%, sublimed
      sulphur 10%, lindane 1%, crotamiton 10% and benzyl benzoate (BB) 10%. Their
      acaricidal activity was measured according to three criteria: (i) for each
      treatment, decrease of Dd to under the normal threshold (< or = 5 D/cm2); (ii)
      for each treatment, a significant decrease in Dd; and (iii) comparison of the
      relative difference in Dd between treatments. These three criteria converged to
      establish the acaricidal activity of BB on D. folliculorum; the efficacy of
      crotamiton was demonstrated by the second criterion. An important irritating
      effect was observed with BB and sulphur.

PMID- 9580801
TI  - Patch testing with preservatives, antimicrobials and industrial biocides. Results
      from a multicentre study.
AB  - Preservatives are biologically reactive substances, and their allergenic
      potential has been known for a long time. This study examined the role of
      different preservatives in a large number of patients with suspected allergic
      contact dermatitis. Patch test data and data from the patients' history were
      collected from the 24 departments participating in the Information Network of
      Departments of Dermatology from 1 January 1990 to 31 December 1994. Patch test
      data from 28,349 patients tested with preservatives of the standard series (SS),
      from 11,485 patients tested additionally with a preservative series (PS), and
      from 1787 patients tested with an industrial biocide tray (IB) were evaluated.
      Sensitization rates (standardized) of the SS preservatives were all > 1%, with
      thiomersal rating highest (5.3%), the parabens lowest (1.6%), and the remainder
      (chlormethylisothiazolinone/methylisothiazolinone, formaldehyde and
      methyldibromoglutaronitrile/phenoxyethanol (MDBGN/PE)) in the range of 2%. The
      most important allergens of the PS were, in women, alkylaminobenzoate (contained
      in milking fat) (2.5%), MDBGN/PE (2.2%), benzalkonium chloride (1.8%),
      chloracetamide (1.4%), diazolidinyl urea (1.3%), octylgallate (1.2%) and Bronopol
      (1.1%). In men rates differed only with regard to alkylaminobenzoate (0.9%).
      Patients tested with the IB series reacted most often to methylene-bis
      thiocyanate (5%), but with a reaction index of -0.7, many reactions were most
      probably false positives. A further seven preservatives, mostly formaldehyde
      releasers used in cutting fluids, gave sensitization rates of between 1% and 3%.
      Glutaraldehyde, not contained in the series but often tested additionally, showed
      a remarkable increase in sensitization during the study period. Health care
      personnel were frequently affected. Altogether, this study identified areas of
      concern within the different groups of preservatives. The overall impact of most
      of the preservatives on public health seems to be low, but for diagnostic reasons
      preservatives must be included in patch test series.

PMID- 9580802
TI  - Pigmentary changes after pulsed dye laser treatment in 125 northern European
      patients with port wine stains.
AB  - We investigated the occurrence of pigmentary changes after flash lamp pumped dye
      laser treatment in 125 Norwegian patients. Post-treatment hyperpigmentation
      occurred with equal frequency during summer and winter (23%), and the facial
      regions did not exhibit higher occurrence than lesions located elsewhere. The
      patients that achieved hyperpigmented skin were not exposed to any higher fluence
      than those without this complication. On the contrary, we found that during the
      summer period from April to September the patients with post-treatment
      hyperpigmentation had been exposed to a significantly lower dose than those
      without pigmentary changes. These results indicate that the epidermal melanin
      content is not the only criterion for obtaining post-treatment hyperpigmentation.
      There might also be a constitutional disposition. In predisposed individuals the
      threshold dose for hyperpigmentation might be reduced in summer when the skin is
      more pigmented.

PMID- 9580803
TI  - Panniculitis in association with apomorphine infusion.
AB  - This study was undertaken to ascertain the histopathology and aetiology of
      cutaneous nodules observed in Parkinson's patients treated with continuous
      subcutaneous apomorphine. Ten patients were recruited, answered questionnaires,
      and underwent skin biopsies and full blood count, and nine were patch tested to
      apomorphine and its preservative. Six had serum IgE levels measured. A florid
      panniculitis was seen in all biopsies; five were predominantly eosinophilic,
      three lymphocytic and two neutrophilic; in seven cases the panniculitis was mixed
      and in three it was septal. Patch testing was universally negative and the IgE
      levels were normal.

PMID- 9580804
TI  - Aspirin-sensitive urticaria: provocation with a leukotriene receptor antagonist.
AB  - The diagnosis of two patients with aspirin-induced urticaria (AIU) was confirmed
      by oral provocation with aspirin, other non-steroidal anti-inflammatory drugs,
      and food additives. Low doses of a novel leukotriene (LT) receptor antagonist,
      ONO-1078 (ONO, Japan) induced urticaria in these patients, while the same doses
      of ONO-1078 did not provoke any eruptions in 10 normal healthy volunteers or five
      patients with aspirin-unrelated chronic urticaria. This is the first report that
      a selective LTD4/LTE4 receptor antagonist that is effective as an antiasthmatic
      agent evoked urticaria in patients with AIU. Our observation suggests that the
      pathogenesis of AIU depends on the stimulation of LT receptors. The accumulation
      of results of anti-LT therapy may provide clues to resolve the pathogenetic
      mechanisms of this disorder.

PMID- 9580805
TI  - Urticarial reaction following the inhalation of nicotine in tobacco smoke.
AB  - We report a patient with recurrent generalized itching and urticaria due to
      inhalation of nicotine in tobacco smoke. A skin prick test with nicotine base
      (1:10 w/v) was negative but an intradermal test with nicotine base (1:100 w/v)
      was strongly positive. Intradermal tests with nicotine base (1:100 w/v) performed
      on 10 healthy controls were negative. A provocation test with a nicotine patch
      showed the same symptoms and signs including generalized itching, weals and
      flares, and mild dyspnoea, which occurred when he was exposed to tobacco smoke.
      Nicotine in tobacco smoke can act as an inhalant allergen and induce urticaria in
      hypersensitive persons.

PMID- 9580806
TI  - Response of severe systemic mastocytosis to interferon alpha.
AB  - Six patients with documented systemic mast cell disease were enrolled in a 1
      year, phase I study to determine the possible benefits of interferon alpha-2b
      (IFN-alpha). IFN-alpha therapy was begun at a dosage of 0.5 million units/day
      (MU/day) by subcutaneous injection and increased, as tolerated, to 3.0 MU/day.
      Subsequent dose modifications were made based on clinical tolerance and response.
      No immediate, adverse reactions to IFN-alpha occurred. Several patients showed
      symptomatic improvement. In two patients ascites resolved and did not recur. Two
      other patients reported improved energy levels and had decreased size of
      retroperitoneal, measenteric and retrocrural nodes. One patient failed to benefit
      and died shortly after completing 12 months of therapy. Bone marrow mastocytosis
      decreased by 5% to 10% after 12 months of therapy with IFN-alpha. Although five
      of the six patients had a decrease in the urinary excretion of 1-methyl-4
      imidazole acetic acid, serum tryptase values did not appreciably change in any
      patient. Side-effects from IFN-alpha included hypothyroidism, thrombocytopenia
      and depression. It is concluded that although treatment with IFN-alpha was
      associated with a decline in bone marrow mastocytosis and reduced excretion of
      histamine metabolites, prolonged therapy may be needed and dose-limiting side
      effects are frequent.

PMID- 9580807
TI  - The photosensitivity dermatitis and actinic reticuloid syndrome (chronic actinic
      dermatitis) occurring in seven young atopic dermatitis patients.
AB  - Seven young patients with atopic dermatitis (AD) who presented with a marked
      photoexposed site dermatitis have been investigated in detail. The results of
      phototesting, patch testing and other investigations were compatible with the
      diagnosis of photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR)
      (chronic actinic dermatitis). It is known that AD patients may have
      photoaggravation of their dermatitis or exacerbation secondary to a
      photodermatosis, such as polymorphic light eruption, actinic prurigo or drug
      induced phototoxicity. The patients we describe, however, appear to be an
      uncommon AD subgroup affected by PD/AR. We recommend that all AD patients who
      have a history of sunlight-induced exacerbation or marked intolerance of PUVA or
      ultraviolet B phototherapy should have phototesting and patch testing conducted.

PMID- 9580808
TI  - Ichthyosiform erythroderma associated with generalized pustulosis.
AB  - Two unrelated boys are described who were born as collodion babies and
      subsequently developed non-bullous ichthyosiform erythroderma and flares of
      generalized sterile pustulosis, similar to generalized pustular psoriasis. Both
      patients had a good response to treatment with oral retinoids.

PMID- 9580809
TI  - Palmoplantar keratoderma associated with congenital heart disease.
AB  - We report the case of a 14-month-old boy suffering from total anomalous pulmonary
      venous connection (TAPVC) associated with congenital diffuse palmoplantar
      keratoderma (PPK). An association between TAPVC and PPK has not been described
      previously, but PPK has been reported in association with a variety of cardiac
      abnormalities. Given the low frequency of both conditions, a genetic link seems
      likely. It is therefore advisable for dermatologists to check for heart
      abnormalities in children with congenital PPK.

PMID- 9580810
TI  - Human papillomavirus 57 identified in a plantar epidermoid cyst.
AB  - We report a 23-year-old Japanese man who had plantar warts on the right sole,
      beneath one of which an epidermoid cyst developed. On microscopic examination, an
      acanthotic epidermis markedly invaginated into the underlying dermis, resulting
      in an open epidermoid cyst. Not only the polymerase chain reaction but also an in
      situ hybridization detected HPV 57 DNA in the cyst. HPV 60 is the only type of
      HPV that has been identified in epidermoid cysts. To our knowledge, this is the
      first case report of an epidermoid cyst, in which a different type of virus from
      HPV 60 was identified. Histological features of the cyst were also different
      those of HPV 60-associated epidermoid cysts.

PMID- 9580811
TI  - Pigmented Bowen's disease.
AB  - We describe two Afro-Caribbean women who presented with pigmented Bowen's
      disease. One, a 44-year-old woman, developed a sharply demarcated, irregularly
      marginated, hyperpigmented plaque with a velvety surface in the perianal area.
      The other, a 25-year-old woman, developed a well defined, verrucous,
      hyperpigmented patch on the umbilicus. Histology showed that both cases were
      Bowen's disease, and subsequent treatment with 5-fluorouracil and cryotherapy led
      to complete resolution.

PMID- 9580812
TI  - Eccrine porocarcinoma with melanocyte colonization.
AB  - We describe a 74-year-old Japanese man with a pigmented eccrine porocarcinoma
      (malignant eccrine poroma). The patient had a brown-black nodule measuring 9 x 7
      mm on his leg. Microscopically, the tumour, which had invaded the reticular
      dermis, was composed of poroid cells with large and small intracytoplasmic
      lumina. The tumour cells showed cytological pleomorphism and frequent, often
      abnormal, mitotic figures. Many dendritic melanocytes containing melanin were
      intermingled with the tumour cells. The poroid cells were diffusely positive for
      cytokeratin, while the dendritic cells containing melanin were positive for S-100
      protein and HMB-45. Ten months of follow-up revealed no recurrence or metastasis
      of the tumour.

PMID- 9580813
TI  - Granulomatous mycosis fungoides with small intestinal involvement and a fatal
      outcome.
AB  - We report a case of granulomatous mycosis fungoides that progressed into fatal
      gastrointestinal involvement 4 years after the onset of skin lesions, despite
      improvement of the skin lesions in response to a combination of PUVA and systemic
      interferon-gamma therapy. Histological examination showed Pautrier's
      microabscesses with granuloma annulare-like features and sarcoidal granuloma
      formation in the plaque stage, proliferation of blast-transformed atypical
      lymphocytes with persistent granuloma formation in the tumour stage, and
      metastatic lesions. A literature review of granulomatous mycosis fungoides
      revealed that 11 of the 24 reported cases died of the disease, and like our case,
      seven died within 5 years. We suggest that mycosis fungoides with granulomatous
      reactions does not indicate a favourable prognosis.

PMID- 9580814
TI  - Post-kala-azar dermal leishmaniasis with mucosal involvement in a kidney
      transplant recipient: treatment with liposomal amphotericin B.
AB  - Post-kala-azar dermal leishmaniasis (PKDL) is a rare clinical variant of
      cutaneous leishmaniasis. It is very common in the Indian subcontinent and less
      frequent in East Africa, but exceptional in the American and European continents.
      We have observed a case of PKDL in a renal transplant recipient. No systemic
      symptoms were present. The patient was treated with liposomal amphotericin B. We
      emphasize the unusual aspects of this case: the appearance of PKDL in Europe, its
      relationship with immunosuppression, the severe mucosal involvement and the
      excellent response to liposomal amphotericin B, a newly described treatment for
      the disease.

PMID- 9580815
TI  - Cutaneous adverse effects associated with terbinafine therapy: 10 case reports
      and a review of the literature.
AB  - Terbinafine is an allylamine antifungal agent widely used to treat dermatophyte
      onychomycosis and dermatomycoses. We report 10 severe cutaneous adverse reactions
      associated with terbinafine therapy which required discontinuation of the
      antifungal agent: erythema multiforme (five patients), erythroderma (one), severe
      urticaria (one), pityriasis rosea (one) and worsening of pre-existing psoriasis
      (two patients). The spectrum of cutaneous adverse effects associated with
      terbinafine therapy is reviewed. Patients should be counselled about
      discontinuing terbinafine at the onset of a cutaneous eruption and about seeking
      medical advice about further management.

PMID- 9580816
TI  - Leg ulceration with associated thrombocytosis: healing of ulceration associated
      with treatment of the raised platelet count.
AB  - Thrombocytosis is the cause of various complications in myeloproliferative
      disorders. We present the case of a 54-year-old woman with chronic myelogenous
      leukaemia who developed large ulcers on both lower legs that were refractory to
      standard treatment. As concomitant thrombocytosis persisted despite treatment
      with hydroxyurea, the new megakaryocyte inhibitor anagrelide (Agrelin) was
      administered and led to normalization of the platelet count within 11 days. The
      leg ulcers started to heal after 2 weeks and disappeared over a period of 5
      months. Our findings argue for a pathogenic role of platelets in the development
      of leg ulcers in patients with thrombocytosis due to a myeloproliferative
      disorder.

PMID- 9580817
TI  - alpha-Melanocyte stimulating hormone inhibits tumour necrosis factor-alpha
      stimulated intercellular adhesion molecule-1 expression in normal cutaneous human
      melanocytes and in melanoma cell lines.
AB  - alpha-Melanocyte stimulating hormone (alpha-MSH) was found significantly to
      reduce tumour necrosis factor-alpha (TNF-alpha) stimulated upregulation of
      intercellular adhesion molecule-1 (ICAM-1) in normal adult cutaneous melanocytes.
      The maximum inhibitory response to alpha-MSH was obtained at around 10(-10) mol/L
      alpha-MSH when cells were coincubated with alpha-MSH and TNF-alpha for 24 h.
      alpha-MSH had little or no effect on basal ICAM-1 expression in melanocytes and
      the effects of alpha-MSH could be mimicked with 3-isobutyl-1-methylxanthine
      (IBMX). Preliminary data in three human melanoma cell lines also showed alpha-MSH
      and forskolin to be effective in significantly reducing TNF-alpha stimulated ICAM
      1 expression over 24 h. The extent of the inhibition varied from cell line to
      cell line and was greatest in those cells with the highest number of alpha-MSH
      receptors. These data suggest that alpha-MSH has the ability to oppose the action
      of the pro-inflammatory cytokine TNF-alpha on melanocytes and melanoma cells.

PMID- 9580818
TI  - Anogenital warts in prepubertal children: a follow-up study.

PMID- 9580819
TI  - Virus characterization studies in eczema herpeticum.

PMID- 9580820
TI  - Human herpesvirus 8 is not detectable by polymerase chain reaction in
      angiosarcoma.

PMID- 9580821
TI  - Childhood bullous pemphigoid associated with chronic renal allograft rejection.

PMID- 9580822
TI  - Bullous pemphigoid induced by bumetanide.

PMID- 9580823
TI  - Pseudoporphyria caused by nabumetone.

PMID- 9580824
TI  - Digital necroses and Sharp's syndrome: the success of topical application of
      granulocyte/macrophage-colony stimulating factor in promoting healing after
      amputation of three toes.

PMID- 9580825
TI  - Panniculitis due to alpha 1-antitrypsin deficiency induced by cryosurgery.

PMID- 9580826
TI  - Hazards of therapy with high doses of N-acetylcysteine for anticonvulsant-induced
      hypersensitivity syndrome.

PMID- 9580827
TI  - Optimizing botulinum toxin therapy for hyperhidrosis.

PMID- 9580828
TI  - Painful subungual tumour in incontinentia pigmenti. Response to treatment with
      etretinate.

PMID- 9580829
TI  - The clinical effect of topical calcipotriol in acrodermatitis continua of
      hallopeau.

PMID- 9580830
TI  - A sporadic case of porokeratosis plantaris palmaris et disseminata.

PMID- 9580831
TI  - Dermatomyositis-like graft-versus-host disease.

PMID- 9580832
TI  - Nasal tip metastasis revealing a Pancoast tumour.

PMID- 9580833
TI  - Lepromatous leprosy presenting as a single doughnut-shaped lesion on the face.

PMID- 9580834
TI  - Maintenance treatment with cyclosporin in psoriasis.

PMID- 9580836
TI  - Sun protection: have we gone too far?

PMID- 9580835
TI  - Renal biopsy findings in long-term cyclosporin treatment of psoriasis.

PMID- 9580837
TI  - Benign masticatory muscle hypertrophy.

PMID- 9580838
TI  - Drug distribution in the training room.
AB  - Individuals providing medications for athletes have a responsibility to provide
      high-quality pharmaceutical care while meeting both legal and ethical
      requirements. Pharmacotherapy monitoring and patient counseling about
      prescription drugs are recent additions to legal requirements in most states.
      Quality control of drug selection, labeling, and packaging as well as optimum
      storage, security, and accountability are essential in promoting positive patient
      outcomes.

PMID- 9580839
TI  - Therapeutic drugs. What to avoid with athletes.
AB  - Sports medicine is a reflection of the type and quality of medicine practiced in
      the community in general. In turn, the practice of medicine is a reflection of
      society, its cultural biases and mores. The use of medication in the treatment of
      athletes requires special consideration on the part of the physician so that the
      athlete is not put in a compromising condition or in jeopardy of
      disqualification. Periodic familiarity with the updated lists of banned
      substances, knowledge of the requisites of the particular sport, and most
      importantly, knowledge of the athletes themselves will help minimize medication
      related problems.

PMID- 9580840
TI  - Recreational drugs.
AB  - The war against substance abuse continues in today's society and the sports world
      often seems to be in the middle of all the attention, especially among the media.
      New recreational drugs arrive on the scene from time to time, much like GHB, but
      the predominant substances of abuse continue to be marijuana, cocaine, and
      alcohol. As research evolves in efforts to stay current and determine any
      potential performance effects of new substances, the literature has changed very
      little regarding the more common recreational drug and their effects on athletic
      participation. New studies are emerging comparing recreational drug use among
      athletes versus nonathletes. Findings include differences among these groups
      regarding individual sports, team sports, contact versus noncontact sports, and
      gender-specific sports. Higher risk-taking behavior contribute to these findings
      and is known to be more prevalent among an athletic population. Overall, illicit
      drug use in America in 1996 remained about the same as in 1995 after rising
      steadily since the early 1990s. About 13 million Americans used drugs at least
      monthly in 1996, up slightly from 12.8 million in 1995. Teenage drug and alcohol
      use fell to 9% in 1996, down from 10.9% in 1995. Attempts to recognize the early
      signs of substance abuse and identify those athletes "at risk" of experimenting
      with elicit drugs are paramount to the optimal treatment response program. The
      preparticipation examination remains the best initial format for establishing a
      sound physician-patient relationship. A thorough history including risk factors,
      family history, and personnel tendencies toward substance abuse should be
      obtained followed by an ongoing relationship between the athlete and his team
      physician. The better rapport between the athlete and team physician, the higher
      likelihood of early recognition of a developing substance abuse problem.
      Likewise, the earliest intervention usually leads to the most optimal treatment
      response.

PMID- 9580841
TI  - Anabolic agents.
AB  - This article provides a comprehensive but practical discussion of four anabolic
      agents used by athletes. Anabolic-androgenic steroids, dehydroepiandrosterone,
      human growth hormone, and insulin-like growth factor are discussed. A thorough
      review of available literature on the basic chemistry and physiology,
      epidemiology, reasons for use, and performance and side effects of each agent are
      also presented.

PMID- 9580842
TI  - Other ergogenic agents.
AB  - Amid the surrounding chaos of the supplement blitz, athlete, coach, and physician
      alike must step back and place the issue of supplements into perspective. There
      is no legal supplement that can substantially alter performance to date in the
      same way as illegal drugs. Effectiveness, safety, legality, and purity of
      compounds are all issues that should be addressed when approaching the use of any
      supplement. Education about the validity of the claims of supplements is
      important. Research is lending useful and helpful information despite the many
      new products continually appearing on the market. Because there is no mechanism
      for investigations to adequately research every supplement, many of the
      supplements should be approached with caution and skepticism. In addition,
      supplements in and of themselves should not be viewed as the sole answer to
      performance improvement. There is some promise to an extremely small number of
      supplements that appear to enhance performance, yet they do so in the realm of
      complete athletic training, including hard work, sports-specific training and
      strength training, psychological preparedness, and good nutritional intake.

PMID- 9580843
TI  - Athletic drug testing.
AB  - A drug-control program requires testing to ensure compliance and to deter use. In
      the athletic drug testing area, measurement of performance-enhancing substances
      is complex partly because of the large number of prohibited substances. A number
      of sophisticated analytical techniques, such as high-resolution mass
      spectrometry, are increasingly used to provide the maximum detection time window.
      Endogenous steroids pose an increasing challenge because of their availability in
      "nutritional supplements". Continued vigilance is required to prevent the
      pharmacologic enhancement of performance.

PMID- 9580844
TI  - Drug programs.
AB  - Drug programs can be a positive method to assist athletes in the decision-making
      process concerning drug use. The keys to a successful drug program include the
      following: (1) inclusion of all involved parties in the development and
      administration of the program, (2) a reliable testing program that is sensitive
      for the drugs banned, (3) a disciplinary program that is consistent, (4) an
      evaluation and treatment program to prevent recurrence of the behavior or one
      that will treat the disease, and (5) the maintenance of confidentiality that will
      foster the confidence and support of all involved parties in the program.

PMID- 9580846
TI  - Pharmacologic treatment of exercise-induced asthma.
AB  - Exercise-induced asthma (EIA) is a complex disorder affecting a sizeable minority
      of athletes. Proper pharmacologic management allows most every athlete at any
      level to participate with EIA. This article briefly addresses the
      pathophysiology, diagnosis, and basic treatment principles, including
      nonpharmacologic management for EIA. Most of the article details the current
      treatment strategies and provides information on experimental treatments being
      investigated. In addition, ergogenic concerns and problems in treating elite
      athletes are discussed.

PMID- 9580845
TI  - Pharmacologic management of athletic amenorrhea.
AB  - Amenorrhea is the absence of menses in reproductive-age women. The female athlete
      can frequently experience amenorrhea during athletic training. This article
      serves as an overview of the possible causes of amenorrhea. Its primary role,
      however, is to focus on both nonpharmacologic and pharmacologic treatment options
      for the female with athletic amenorrhea.

PMID- 9580847
TI  - The team physician's bag.
AB  - This article discusses the choices to be made by the team physician before
      venturing out on the road with the team, including an analysis of hardware from
      the actual travel kit to the supplies needed. Typical problems encountered are
      reviewed in context to preparing the medications that will be carried on the
      road. Organization and periodic review of needs and supplies is vital to a
      successful trip.

PMID- 9580848
TI  - Pharmacologic management of pain and inflammation in athletes.
AB  - This article attempts to concisely present some of the scientific basis of the
      pharmacology of anti-inflammatory medications. The clinical use and application
      of anti-inflammatories is also addressed. The information is designed to assist
      the clinician to develop a sound approach in selecting the appropriate treatment
      plan for their patients.

PMID- 9580849
TI  - Treatment of advanced (stages III and IV) non-small-cell lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths, and approximately 85% of
      patients in whom this neoplasm is diagnosed will die of this disease as a result
      of micrometastatic disease from tumors that appeared surgically resectable or of
      surgically unresectable disease that is either locally advanced or metastatic. It
      will affect approximately 171,000 people in the United States in 1998 and about
      75% of these cases will be non-small-cell lung cancer (NSCLC). In only 25% of
      cases can complete surgical resection and cure be considered. Despite this grim
      outlook, advances have recently been made that beckon in an era of cautious
      optimism. In this review, a discussion of the latest developments in the
      management of locally advanced and metastatic NSCLC will be presented in detail.
      One of the significant developments has been the modifications to the staging
      system after the natural history of various stages was better characterized by
      reviewing the outcome of more than 5000 patients. Advances have also been seen in
      the diagnostic field. Specifically, positron emission tomography and endoscopic
      ultrasonography and biopsy are being evaluated to determine their role in
      diagnosing and staging lung cancer. At the present, however, history and physical
      examination, serum evaluation, computed tomography, and conventional approaches
      for obtaining a histologic diagnosis are standard practice. The role of adjuvant
      therapy, both postoperatively and in the neoadjuvant setting, has been studied.
      There are no data to support the use of radiotherapy or chemotherapy, with or
      without radiotherapy, in the postoperative setting. In the neoadjuvant setting,
      some intriguing results in favor of adjuvant chemotherapy have been observed. As
      discussed in detail these results provide preliminary data and need to be
      evaluated on a larger scale. Before the 1990s radiotherapy was the principal
      treatment modality used in the treatment of patients with locally advanced NSCLC.
      However, the results of several studies have shown the superiority of
      chemotherapy and radiotherapy in combination for patients with unresectable stage
      III NSCLC. Many questions regarding the optimal modes of chemotherapy and
      radiotherapy and the timing of these two modalities have yet to be answered.
      Concurrent with these advances has been the development of new chemotherapeutic
      agents that have been extensively evaluated in phase I and II trials. These
      agents include gemcitabine, paclitaxel, docetaxel, vinorelbine, and irinotecan.
      These agents have shown significant activity and acceptable toxicity when used in
      combination with cisplatin or carboplatin, but the results from the large
      cooperative trials that are ongoing are eagerly awaited to help define the
      optimal regimen. Further studies are either planned or ongoing to further define
      the role of these newer agents in the treatment of metastatic disease, in
      combination with radiotherapy for unresectable disease, and in the surgical
      adjuvant setting.

PMID- 9580850
TI  - Thyroid stunning.

PMID- 9580851
TI  - Comparison of cellular and conventional dosimetry in assessing self-dose and
      cross-dose delivered to the cell nucleus by electron emissions of 99mTC, 123I,
      111In, 67Ga and 201T1.
AB  - The radionuclides used in nuclear medicine imaging emit numerous mono-energetic
      electrons responsible for dose heterogeneity at the cellular level. S(self) the
      self-dose per unit cumulated activity (which results from the radionuclide
      located in the target cell), and S(cross) the cross-dose per unit cumulated
      activity (which comes from the surrounding cells) delivered to a target cell
      nucleus by electron emissions of technetium-99m, iodine-123, indium-111, gallium
      67 and thallium-201 were computed at the cellular level. An unbounded close
      packed hexagonal cell arrangement was assumed, with the same amount of
      radioactivity per cell. Various cell sizes and subcellular distributions of
      radioactivity (nucleus, cytoplasm and cell membrane) were simulated. The results
      were compared with those obtained using conventional dosimetry. S(self) and
      S(cross) values depended closely on cell dimensions. While the self-dose depended
      on the tracer distribution, the latter affected the cross dose by less than 5%.
      When the tracer was on the cell membrane, the self-dose was particularly low
      compared to the cross-dose, as the self-dose to cross-dose ratio was always less
      than 11%. In the case of cytoplasmic or cell membrane distribution of
      radioactivity, conventional electron dosimetry slightly overestimated the dose
      absorbed by the target cell nucleus (by 1.08-to 1.7-fold). In contrast,
      conventional dosimetry strongly underestimated the absorbed dose (1.1- to 75
      fold) when the radioactivity was located in the nucleus. The discrepancies
      between conventional and cellular dosimetry call for calculations at the cellular
      level for a better understanding of the biological effects of radionuclides used
      in diagnostic imaging.

PMID- 9580852
TI  - Median root prior and ordered subsets in Bayesian image reconstruction of single
      photon emission tomography.
AB  - Median root prior allows Bayesian image reconstruction without any a priori
      knowledge of the final solution. It limits the noise generated by maximum
      likelihood-expectation maximization, including when the ordered subsets
      accelerating procedure is used. Therefore the number of iterations can be
      optimized to obtain the best resolution for cold lesions. Moreover, the higher
      the number of subsets, the better the contrast, with optimal results for subsets
      containing between four and eight projections.

PMID- 9580853
TI  - Attenuation-corrected thallium-201 single-photon emission tomography using a
      gadolinium-153 moving line source: clinical value and the impact of attenuation
      correction on the extent and severity of perfusion abnormalities.
AB  - The aim of the study was to test the clinical value of attenuation-corrected (AC)
      thallium-201 single-photon emission tomography using a moving gadolinium-153 line
      source in a group of patients in whom coronary angiography was planned because of
      clinically suspected coronary artery disease (CAD). Furthermore, we wanted to
      test the impact of AC on assessment of the extent and severity of perfusion
      abnormalities. A total of 107 patients planned to undergo coronary angiography
      were included in the study. In each patient, AC and NC (non-corrected) 201Tl SPET
      was performed. AC and NC images were evaluated visually as well as by a 31
      segment semiquantitative analysis and the findings were correlated with
      angiographic results. Patients were assigned to two groups: group A with angina
      and no previous cardiac infarction or intervention and group B with known CAD
      because of previous myocardial infarction or intervention. With visual analysis,
      NC revealed a sensitivity of 88.9% in group A and 74.3% in group B, compared to
      94.4% in group A and 94.3% in group B with AC. Specificity for NC was calculated
      to be 68.7% for group A and 91.3% for group B. AC demonstrated significantly
      higher specificity of 83.9% and 100% respectively. This effect was particularly
      demonstrated for males and bicycle workload. The extent and severity of perfusion
      abnormalities were significantly influenced by the use of AC, in that
      significantly fewer abnormal and less severely abnormal segments were
      demonstrated in the segmental analysis as compared to NC; this was especially
      true for the vascular territory of the left anterior descending artery and the
      right coronary artery. It is concluded that AC with a moving line source is
      feasible in patients with all degrees of probability of CAD. AC has a significant
      impact on the assessment of the severity and extent of myocardial ischaemia,
      especially in the posterior and septal wall.

PMID- 9580854
TI  - Value of iodine-123 metaiodobenzylguanidine scintigraphy in patients with
      vasospastic angina.
AB  - To assess the presence and location of presynaptic myocardial sympathetic
      abnormality in patients with vasospastic angina, iodine-123 labelled
      metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET) was
      performed. Fifty patients suspected of having vasospastic angina pectoris were
      enrolled in the study. All patients underwent a provocative test with
      intracoronary ergonovine infusion during coronary angiography, in which 99%-100%
      obstructive spasm was defined as a positive result. Twenty-five patients were
      diagnosed as having vasospastic angina based on a positive provocative test. MIBG
      SPET was performed at 20 min and 3 h after administration of 111 MBq or MIBG. On
      early images, only 5 of 25 patients with vasospastic angina showed a mild
      reduction in MIBG uptake, whereas 3-h delayed images demonstrated MIBG
      abnormality in 20 patients (80%). The location of the MIBG abnormality was
      completely or partially consistent with the spastic coronary territory in 18
      patients. On the other hand, only 4 of 25 patients (16%) with negative
      provocative test demonstrated reduced MIBG uptake. Accordingly, positive and
      negative predictive values of MIBG SPET for the provocative test were 83% (20/24)
      and 81% (21/26) respectively. In conclusion, MIBG scintigraphy with SPET can
      permit the non-invasive detection and evaluation of suspected vasospastic angina.

PMID- 9580855
TI  - Impact of exercise rehabilitation on cardiac neuronal function in heart failure:
      an iodine-123 metaiodobenzylguanidine scintigraphy study.
AB  - Exercise training can induce important haemodynamic and metabolic adaptations in
      patients with chronic heart failure due to severe left ventricular dysfunction.
      This study examined the impact of exercise rehabilitation on cardiac neuronal
      function using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, Fourteen
      patients (11 men, 3 women; mean age 48 years; range: 36-66 years) with stable
      chronic heart failure of NYHA class II-III and an initial resting radionuclide
      left ventricular ejection fraction (LVEF) < 50% were enrolled in the study.
      Patients underwent progressive, supervised endurance training (treadmill test,
      Bruce protocol) during a 6-month period (60 sessions, 3 sessions per week) at a
      cardiac rehabilitation referral centre in order to measure exercise parameters.
      Planar 123I-MIBG scintigraphy provided measurements of cardiac neuronal uptake
      (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of
      MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of
      exercise training. Workload (801 +/- 428 vs 1229 +/- 245 kpm.min-1, P = 0.001),
      exercise duration (504 +/- 190 vs 649 +/- 125 s, P = 0.02), and myocardial MIBG
      uptake (135% +/- 19% vs 156% +/- 25%, P = 0.02) increased significantly after
      rehabilitation. However, LVEF did not change significantly (23% +/- 9% vs 21% +/-
      10%, p = NS). It is concluded that exercise rehabilitation induces improvement of
      cardiac neuronal function without having negative effects on cardiac
      contractility in patients with stable chronic heart failure.

PMID- 9580856
TI  - Decreased uptake of therapeutic doses of iodine-131 after 185-MBq iodine-131
      diagnostic imaging for thyroid remnants in differentiated thyroid carcinoma.
AB  - We performed a prospective random study to assess possible thyroid stunning by a
      185-MBq iodine-131 dose used to diagnose thyroid remnants. Patients with
      differentiated thyroid carcinoma were included after total or near-total
      thyroidectomy. They were randomly assigned to two groups. In group 0 (G0, 32
      patients), iodine-123 administration only was used to diagnose thyroid remnants
      and/or metastasis, so that no thyroid stunning by 131I would occur. In group 1
      (G1, 19 patients), diagnostic imaging was performed with 123I and 185 MBq 131I.
      123I imaging was less sensitive than 131I imaging in identifying thyroid remnants
      in both groups (94%). Thyroid uptake of 123I was measured in both groups (at 2 h)
      and was not significantly different between the groups. Patients with thyroid
      remnants who remained in the study (28/32 in G0, 17/19 in G1) were treated with
      370 MBq 131I, 5 weeks after treatment (mean time, range 12-84 days). In 12/17 G1
      patients thyroid uptake measurement was repeated immediately before treatment.
      Uptake was equal to 1.97% +/- 0.71% and significantly lower (P < 0.05) than the
      previous measurement (3.76% +/- 1.50%). Patients were imaged 7 days after
      administration of the therapeutic dose and the images were compared with the
      diagnostic images. In 28/28 G0 patients thyroid remnants were unchanged and
      clearly seen. In 5/17 G1 patients, however the remnants were hardly identified,
      although they had been clearly seen at the time of diagnosis. We conclude the
      following: (1) a diagnostic dose of 185 MBq 131I decreases thyroid uptake for
      several weeks after administration and can impair immediate subsequent 131I
      therapy; (2) 123I is slightly less sensitive than 131I in identifying thyroid
      remnants; and (3) the need to scan for thyroid remnants remains to be confirmed,
      since only 2/51 patients enrolled in this study were not treated with 131I.

PMID- 9580857
TI  - Role of indium-111 labelled platelet scintigraphy in the management of
      thrombocytopenic patients with malignant neoplasms.
AB  - This study was done to investigate the role of indium-111 labelled platelet
      scintigraphy in the treatment of thrombocytopenia in patients with malignant
      neoplasms. The study involved 20 consecutive patients with thrombocytopenia
      associated with malignant neoplasms of hematological disorders and without
      evidence of underproduction of megakaryocytes due to chemotherapy or bone marrow
      infiltration by the malignancy. Splenic sequestration of platelets was evaluated
      by measuring splenic uptake of 111In-labelled platelets, and findings were
      correlated with the outcome of splenectomy and medication. Of the 20 patients, 13
      had splenic sequestration of platelets. Seven of the 13 patients underwent
      splenectomy; six of these seven patients experienced a complete response. The
      other six patients received medication only and showed no response. Of the seven
      patients without splenic sequestration of platelets, five received medication,
      and four of them responded to it. 111In-labelled platelet scintigraphy has a role
      in selecting appropriate therapy and predicting its efficacy in patients with
      thrombocytopenia associated with malignant neoplasms.

PMID- 9580858
TI  - The limited role of myocardial fluorine-18 fluorodeoxyglucose imaging in
      candidates for cardiac transplantation: a planar imaging study.
AB  - This study compares the incidence and extent of hibernating myocardium (defined
      by myocardial perfusion/metabolism mismatch) in 28 cardiac transplant candidates
      with ischaemic cardiomyopathy and in 16 other patients with coronary artery
      disease (CAD) undergoing viability assessment. It then reviews the impact of
      myocardial perfusion metabolism imaging on management decisions in the transplant
      candidates at 6 months after scintigraphy. Each patient underwent a planar
      myocardial thallium-201 and fluorine-18 fluorodeoxyglucose scan on a modified
      gamma camera. Perfusion/metabolism mismatch was sized semi-quantitatively and
      each patient was assigned a global mismatch score. Transplant candidates had a
      lower left ventricular ejection fraction (LVEF) (P < 0.0002) and extent of
      hibernation myocardium (lower global mismatch score: P = 0.005) than other CAD
      patients but the difference in respect of mismatch frequency (8/28 vs 9/16
      patients) did not reach statistical significance. Transplant candidates with LVEF
      < 20% had a lower global mismatch score (P < 0.02) than those with an LVEF > or =
      20%. Interestingly two of three other CAD patients with LVEF < 20% had a moderate
      mismatch. Follow-up studies revealed the lack of impact of metabolic imaging as
      none of the three transplant candidates who eventually underwent
      revascularisation had hibernating myocardium and transplantation was offered to
      one of only two candidates with more than one minor mismatch. Thus metabolic
      imaging in potential transplant candidates may be of limited value because of the
      very low extent of hibernating myocardium, particularly if LVEF is below 20% and
      where clinical decisions are often based on many other factors.

PMID- 9580859
TI  - Focal fluorine-18 fluorodeoxyglucose accumulation in inflammatory pancreatic
      disease.
AB  - Focal 2-deoxy-2[fluorine-18]fluoro-D-glucose (FDG) uptake on positron emission
      tomography (PET) in a pancreatic mass has been reported as a specific finding for
      pancreatic carcinoma. Inflammatory conditions of the pancreas and associated
      clinical circumstances yielding similar findings have not yet been fully defined.
      Among 42 patients studied by attenuation-corrected FDG PET for pancreatic
      disease, 12 with focal FDG uptake in the pancreas were identified as having no
      underlying neoplasm based on surgical findings, biopsy results, and long term
      clinical and imaging follow up. Focal FDG accumulation in the pancreas with
      standardized uptake values ranging from 3.4 to 11.2 on FDG PET was ultimately
      found to be related to inflammation rather than neoplasm. This occurred in
      pancreatic masses in which clinical and laboratory evidence of acute pancreatitis
      was equivocal or entirely lacking, as well as in the setting of acute
      pancreatitis and after recovery from acute pancreatitis. Inflammation can give
      rise to focal FDG uptake in the same intensity range as pancreatic neoplasm, even
      when clinical, laboratory and computed tomographic findings suggestive of an
      inflammatory etiology are equivocal or absent.

PMID- 9580860
TI  - Prostaglandins as biochemical markers of radiation injury to the salivary glands
      after iodine-131 therapy?
AB  - Because salivary glands, as well as thyroid tissue, are able to concentrate
      radioiodine, the treatment of thyroid diseases with iodine-131 may have secondary
      effects on salivary gland function which seriously impair the quality of life.
      Such effects include sialoadenitis and xerostomia. Salivary secretion is
      stimulated by prostaglandins (PGs). In this study we evaluate whether 131I
      therapy influences the levels of PGs in saliva. Patients who had previously
      received 131I for treatment of hyperthyroidism or differentiated thyroid cancer
      and healthy volunteers were studied. Levels of PGs [6-oxo-PGF1 alpha, bicyclo
      PGEm, thromboxane B2 (TXB2), PGF2 alpha] in unstimulated saliva were measured
      using enzyme immunoassay. Significantly lower levels of 6-oxo-PGF1 alpha, bicyclo
      PGEm and PGF2 alpha and higher levels of TXB2 were found in the group of patients
      in comparison with the controls. Differences between patients and controls were
      more pronounced in smokers. This study demonstrates that salivary gland uptake of
      131I significantly affects PG levels in saliva.

PMID- 9580861
TI  - Pulmonary embolism exclusion: a practical approach to low probability using the
      PIOPED data. Prospective Investigation of Pulmonary Embolism Diagnosis.
AB  - A recent trend among physicians is the categorisation of lung scans as normal
      [excludes pulmonary embolism (PE)], high probability (confirms PE) and non
      diagnostic (no judgement on PE risk). The low probability scan is therefore being
      eliminated as a functional category. This occasional survey contends that such an
      approach is misguided. Correction of the original PIOPED data with certain
      assumptions provides a more reproducible, albeit restricted, low probability scan
      category which excludes PE in 97% of cases in the low pre-test clinical category.
      Patients with a low probability scan with risk factors for PE (i.e. medium
      clinical risk) will require further investigation. More important, the very low
      probability scan category excludes PE in 98% of patients with low and more than
      92% of patients with medium pre-test clinical likelihood. The demise of "low
      probability" is premature.

PMID- 9580862
TI  - The mechanism of accumulation of tumour-localising radiopharmaceuticals.

PMID- 9580863
TI  - Statistical parametric mapping in whiplash brain: is it only a contusion
      mechanism?

PMID- 9580864
TI  - The true clinical significance of renography in nephro-urology.

PMID- 9580866
TI  - Negotiating the parameters of nuclear regulation: who should be in charge?

PMID- 9580865
TI  - Supervising nuclear medicine procedures: who, how, and how often.

PMID- 9580867
TI  - Nuclear Medicine Department at Ga-Rankuwa Hospital MEDUNSA, Gauteng, Republic of
      South Africa.

PMID- 9580868
TI  - Nuclear medicine at Tygerberg Hospital, Cape Town, South Africa.

PMID- 9580869
TI  - Pilot study proposal for a distance education programme for nuclear medicine
      technologists in Africa.

PMID- 9580870
TI  - A cost-utility analysis of interferon beta for multiple sclerosis.

PMID- 9580871
TI  - Effect of in vivo administered 2,3,7,8-tetrachlorodibenzo-p-dioxin on DNA-binding
      activities of nuclear transcription factors in liver of guinea pigs.
AB  - To study the long-term effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on
      the DNA-binding activity of nuclear transcription factors; a single dose of TCDD
      was injected intraperitoneally to male guinea pigs (1 microgram/kg i.p.). The
      animals were killed after 1, 2, 10, 20, 28, and 40 days, and DNA-binding
      activities in liver nuclear fraction were assessed through electrophoretic gel
      mobility shift assay (EMSA). As expected, the nuclear protein binding to dioxin
      or xenobiotic response element (DRE or XRE) increased as a result of TCDD's
      action (1-20 days). In addition, protein binding to 32P-labeled activator protein
      1 (AP-1) response element (RE) (1-28 days) and activator protein-2 (AP-2) RE (1
      28 days) were all increased by the action of TCDD. On the other hand, TCDD
      treatment significantly lowered the nuclear protein binding to both specific
      protein-1 (Sp-1) RE and c-MycRE at all time points (1-40 days). In the case of
      protein binding to 32P-labeled cAMP response element (CRE), we found two groups
      of binding bands being affected by TCDD. The intensity of the upper band group
      decreased, and that of the lower band group increased. As for AP-1 proteins,
      judging by the results of the Western blotting assay, the level of c-Fos
      increased while that of c-Jun decreased with TCDD treatment both at day 1 and 28.
      It is known that the rise in AP-1 and AP-2 activities often results in lowering
      certain cell differentiation signaling messengers in the nucleus. In agreement
      with this scenario, binding of C/EBP (CCAAT enhancer binding protein) to its
      response element site was found to be suppressed for 1 through 28 days. Among
      hormone receptors, TCDD treatment decreased the binding to retinoic acid RE but
      increased the binding to thyroid hormone RE.

PMID- 9580872
TI  - Molecular cloning, sequence, and expression of mouse flavin-containing
      monooxygenases 1 and 5 (FMO1 and FMO5).
AB  - Full-length cDNA clones encoding FMO1 and FMO5 have been isolated from a library
      constructed with mRNA from the liver of a female CD-1 mouse. The derived sequence
      of FMO1 contains 2310 bases: 1596 in the coding region, 301 in the 5'-flanking
      region, and 413 in the 3'-flanking region. The sequence for FMO5 consists of 3168
      bases; 1599 in the coding region, 812 in the 5'-flanking region, and 757 in the
      3'-flanking region. The sequence of FMO1 encodes a protein of 532 amino acids
      with a predicted molecular weight of 59.9 kDa and shows 83.3% identity to human
      FMO1 and 83-94% identity to other FMO1 homologs. FMO5 encodes a protein of 533
      amino acids with a predicted molecular weight of 60.0 kDa and 84.1% identity to
      human FMO5 and 83-84% identity to other FMO5 orthologs. Two GxGxxG putative
      pyrophosphate binding domains exist beginning at positions 9 and 191 for FMO1,
      and 10 and 192 for FMO5. Mouse FMO1 and FMO5 were expressed in E. coli and show
      similar mobility to the native proteins as determined by SDS-PAGE. The expressed
      FMO1 protein showed activity toward methimazole, and FMO5 was active toward
      noctylamine. In addition, FMO1 was shown to metabolize radiolabeled phorate,
      whereas FMO5 showed no activity toward phorate.

PMID- 9580873
TI  - Purification and properties of soman-hydrolyzing enzyme from human liver.
AB  - A soman-hydrolyzing enzyme (somanase) was purified from human liver. The human
      somanase is capable of hydrolyzing pinacolyl methylphosphonofluoridate (soman),
      diisopropylphosphorofluoridate (DFP), and ethyl-N-dimethyl phosphoramidocyanidate
      (Tabun) with P-F or P-CN bonding, but not ethyl (S-2-diisopropylaminoethyl)
      methylphosphonothiolate (VX) and diethyl-p-nitro-phosphenylphosphate (paraoxon)
      with P-S or P-O bonding. The somanase has been purified 1570-fold with a specific
      activity of 41.4 mumol/min/mg protein. Its molecular weight is around 58 kDa
      determined by SDS-PAGE. The somanase could be stimulated by the divalent cations
      Mn+2, Mg+2, and Co+2, where CO+2 activation is the highest. The requirement of
      disulfide bonds for the enzyme activity was demonstrated by the inhibition effect
      of DTT.

PMID- 9580874
TI  - Streptozotocin-induced diabetes increases gamma-glutamyltranspeptidase activity
      but not expression in rat liver.
AB  - Earlier work describing increased biliary excretion of the acetaminophen-cysteine
      conjugate advanced the hypothesis that streptozotocin-induced diabetes increases
      gamma-glutamyltranspeptidase (GGT) expression in Sprague-Dawley rats. To test
      this hypothesis, rats were divided into control, diabetic, and insulin-treated
      diabetic groups. Diabetes was induced by intravenous injection of 45 mg
      streptozotocin/kg body weight and was effectively controlled by insulin treatment
      in the appropriate group. Densitometric quantification demonstrated that hepatic
      GGT activity in diabetic rats was significantly increased when compared to normal
      and insulin-treated diabetic controls. Histochemical staining of liver was
      greater in female than in male rats, and staining increased in female rat liver
      as the duration of diabetes lengthened from 30 to 90 days. GGT activity was
      increased by diabetes in liver canalicular-enriched and basolateral-enriched
      membrane preparations, and it was unchanged in renal brush border-enriched
      membranes. Total mRNA isolated from diabetic and insulin-treated diabetic rat
      livers did not conclusively demonstrate an elevation of GGT mRNA relative to
      normal. Western blot analysis showed no differences in the amount of GGT in
      diabetic versus normal rat livers. These data indicate that streptozotocin
      induced diabetes does not alter the expression of, but does increase the activity
      of, GGT in liver.

PMID- 9580875
TI  - Effects of potassium antimony tartrate on rat erythrocyte phosphofructokinase
      activity.
AB  - In an earlier study, we observed a marked accumulation of antimony in
      erythrocytes of rats administered potassium antimony tartrate (Sb) in drinking
      water. This observation has raised concerns of possible adverse effects on the
      hematological systems. A study was therefore carried out to investigate the
      effects of Sb on phosphofructokinase (PFK), a rate-limiting enzyme of erythrocyte
      glycolysis. Preincubation of PFK with Sb caused a marked inhibition of the enzyme
      with 95% loss of activity at 5 mM. In comparison, 5 mM sodium arsenite, a known
      enzyme inhibitor, reduced PFK activity by only 38%. Increasing the concentrations
      of fructose-6-phosphate (F6P) or magnesium had no effects on the inhibitory
      potency of Sb. Varying the concentrations of ATP and Sb produced a complex effect
      on PFK activity. At 1 mM ATP, 0.2 mM Sb was required for 50% inhibition (IC50) of
      PFK but only 0.05 mM Sb was required for the same inhibition when the
      concentration of ATP was reduced to 0.2 mM. Glutathione (2-10 mM) and hemoglobin
      (8-40 micronM partially protected the enzyme from the Sb effect, with the
      protection being more effective at low antimony concentrations. When Sb was added
      to assay mixtures after initiation of a PFK reaction with physiological
      concentrations of ATP (0.2 mM) and F6P (0.1 mM), PFK activity was approximately
      50% inhibited by 0.5 mM Sb and completely inhibited by 5 mM Sb. In contrast,
      glucose utilization in whole blood was only 16% lower over an 8 hour incubation
      period in the presence of 5 mM Sb. It is concluded that while PFK is markedly
      inhibited by Sb under in vitro assay conditions, glycolysis in erythrocytes is
      not significantly affected except at very high Sb concentrations. The weak effect
      of Sb on glycolysis in erythrocytes may be due in part to the protective effect
      of hemoglobin and, to a lesser extent, glutathione on PFK.

PMID- 9580876
TI  - Antioxidant and detoxifying enzymes in the liver and kidney of pheasants after
      intoxication by herbicides MCPA and ANITEN I.
AB  - The activity of antioxidant and detoxifying enzymes, such as superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GSHPx), glutathione reductase,
      glutathione-S-transferase (GST), the contents of thiobarbituric acid reactive
      substances, and the superoxide dismutase and glutathione-S-transferase isoenzyme
      patterns, were determined in the liver and kidney of pheasants after acute
      intoxication by herbicides MCPA and ANITEN I. In the liver, the activity of
      antioxidant enzymes was significantly decreased in the group given ANITEN I. New
      superoxide dismutase isoforms (pI 6.30, 6.85, 7.00) and higher intensity of
      isoform with pI 6.60 were observed after isoelectrofocusing in all experimental
      groups. In the kidney, the activity of superoxide dismutase was significantly
      decreased, and a higher intensity of superoxide dismutase isoforms (pI 6.00 and
      6.60) was observed in all experimental groups. The contents of thiobarbituric
      acid reactive substances were significantly increased in the group with ANITEN I.
      The glutathione-S-transferase isoenzyme pattern was studied by using subunit
      specific substrates and by Western blotting. The activity of glutathione-S
      transferase with ethacrynic acid and cross-reactivity with rat subunit 7 was
      lower in all experimental groups in the kidney and liver, except in the liver of
      the group given a higher dose of ANITEN I. In this group, we have found a 2.10
      fold higher activity to ethacrynic acid and a strong induction of subunit 7.

PMID- 9580877
TI  - Sensitivity of bovine retinal acetylcholinesterase (E.C. 3.1.1.7) toward tacrine:
      kinetic characterization.
AB  - This work addresses the kinetic analysis of the interaction of tacrine with
      bovine retina acetylcholinesterase (A ChE, E.C. 3.1.1.7). It was found that the
      tacrine effect was reversible in nature. Tacrine inhibited bovine retinal AChE
      activity in a concentration-dependent manner; IC50 was fo to be 8.07 nM. The
      Michaelis-Menten constant (Ka) for the hydrolysis of acetylthiocholine iodide
      (ASCh) by AChE was 0.061 mM in the control system, and this value was increased
      by 54-67% in the tacrine-treated systems. The Vmax was 0.701 mumole/min per
      milligram protein for the control system, but it was decreased by 26-69% in the
      tacrine-treated systems. The Lineweaver-Burk plot, Dixon plot, and their
      secondary replots indicated that the nature of the inhibition was of the partial
      mixed type, that is, a mixture of competitive and noncompetitive inhibition. The
      values of Ki and Kt were estimated to be as 4.475 and 8.517 nM, respectively.

PMID- 9580879
TI  - Clinical significance of hepatic HCV RNA in patients with chronic hepatitis C
      demonstrating long-term sustained response to interferon-alpha therapy.
AB  - Whether sustained biochemical response and absence of serum HCV RNA in the 6-12
      months following suspension of interferon-alpha (IFN-alpha) therapy reflect
      definitive viral clearance in patients with chronic hepatitis C virus (HCV)
      infection is controversial. To obtain more information on this topic, HCV RNA was
      sought in both liver and serum samples of 25 long-term responders who were
      followed for a median period of 39 months (range 21-79) after discontinuation of
      IFN-alpha. Liver biopsy was undertaken before and 6 to 12 months after IFN-alpha
      withdrawal. Liver and serum HCV RNA were tested by a nested polymerase chain
      reaction. Twenty-two patients (88%) tested negative for both liver and serum HCV
      RNA, two patients had detectable HCV RNA in both liver and serum, and one patient
      showed persistent HCV RNA only in the liver. Post-treatment liver histology
      improved markedly in all patients, including those with viral persistence. During
      further follow-up, biochemical remission was maintained in all patients except
      one in whom both serum and liver specimens remained HCV RNA positive. The data
      indicate that the large majority of long-term responders test negative for HCV
      RNA in the liver, which suggests definitive eradication of HCV RNA infection.

PMID- 9580878
TI  - Detection of hepatitis C virus core protein circulating within different virus
      particle populations.
AB  - Progress in studying pathogenesis and increasing the reliability of hepatitis C
      diagnosis can be achieved by analysis of different forms of virus particles
      circulating in blood of both patients and infected persons. Detection of
      hepatitis C virus (HCV) proteins faces two basic difficulties: low concentration
      of HCV proteins, and their blocking by antibodies. The aim of this work was to
      develop a method for the detection of nucleocapsid (core) protein in the plasma
      of HCV-infected persons using monoclonal antibodies (MABs). Twenty-seven anti-HCV
      positive donor plasmas were studied of which 21 contained HCV RNA and 6 were
      negative. The plasmas were centrifuged for 3 hr at 143,000 g and the antigenic
      activity of core-protein was studied in the pellets by EIA using four MABs able
      to recognize four nonoverlapping determinants, two at N-terminus and two at C
      terminus of recombinant core (1-150 aa). The determinants detected were present
      in the natural core protein of at least two genotypes (1b and 3a). Maximal
      efficiency of recombinant protein detection was achieved with 2 MABs, whereas a
      combination of 4 MABs was necessary for optimal detection of natural core
      protein. This is indicative of different conformational structures of natural
      protein and its gene-engineered analog. The sensitivity of core detection by
      monoclonal sandwich assay was 1 ng/ml in the pellet or 5 pg/ml after
      normalization to the initial plasma volume. To dissociate immune complexes, the
      pellet was treated with 2.5 M KBr after first treating the pellet with the
      nonionic detergent Tween 80 to remove the virus lipid envelope. Using this
      treatment protocol, core protein was found in 19 of 21 RNA positive plasmas.

PMID- 9580880
TI  - Floating density of hepatitis C virus particles and response to interferon
      treatment.
AB  - Hepatitis C virus (HCV) particles can be classified into two major fractions
      according to their floating density in serum. However, the genomic heterogeneity
      of each fraction and the relationship between this viral characteristic and
      interferon (IFN) response in patients with chronic hepatitis are not known. In
      this study, floating density and single strand conformation polymorphism (SSCP)
      of the hypervariable region 1 (HVR1) of HCV were examined in 16 patients with
      chronic hepatitis prior to IFN treatment. The ratio of HCV RNA titers in the top
      (T) and bottom (B) fractions, or T:B ratio, was 10:1 in 4 patients, 1:1 in 7, and
      1:10 in 5. Three of the 4 patients with a 10:1 ratio showed a sustained response
      to IFN, while none of the 5 patients with a 1:10 ratio demonstrated a sustained
      response (P < 0.05). All 4 patients with a 10:1 ratio had 1 or 2 SSCP bands, and
      4 of the 5 patients with a 1:10 ratio had 4 or 5 bands (P < 0.01). Furthermore,
      the number of SSCP bands in the top fraction from 6 sustained responders (1.8 +/-
      0.3) was significantly smaller than from 10 non sustained responders (4.1 +/-
      0.8) (P < 0.05). Thus, patients with a high T:B ratio and low heterogeneity in
      HVR1 demonstrated sustained responses to IFN, while those with low T:B ratios and
      high heterogeneity did not.

PMID- 9580881
TI  - Large-scale analysis of hepatitis C virus serological typing assay: effectiveness
      and limits.
AB  - The HCV (hepatitis C virus) Serotyping 1-6 Assay (Murex Laboratories) was
      evaluated on 303 French HCV-infected patients. Serological typing results were
      compared to the genotypes obtained from sequence analyses of the 5' noncoding
      regions of the virus genome from 46 HCV-infected patients, and assay specificity
      was found to be high (97.6%). The serological typing assay, run in 257
      consecutive HCV-infected patients, yielded an assay sensitivity lower (70.6%)
      than that previously reported. This finding was attributed mainly to nonreactive
      sera from human immunodeficiency virus (HIV)-positive patients (P < 0.001) and
      perhaps reflected cryoglobulin positivity in others. No anti-type 6 reactivity
      was detected, and the overall serological type distribution values for types 1 to
      5 were 67.3, 7.9, 16.4, 6.6, and 0.9%, respectively. A higher prevalence of type
      4 was noted among HIV-infected patients (P < 0.001). In addition, serotype 2 was
      significantly more frequent in cryoglobulinemia positive than in cryoglobulinemia
      negative patients (P < 0.05). Although an initial high level (7%) of mixed
      serological typing reactivities was found, after predilution of serum only two
      mixed infections could be confirmed (0.9%). It is suggested, therefore, that
      mixed reactivities have to be interpreted carefully and retested with prediluted
      serum, particularly when the optical density of the reactivity is > 2.5 or
      remains > 0.4 after competition with all type-specific peptides. The high
      specificity and relatively good sensitivity even in immunocompromised patients
      obtained with this assay indicate that it can be used routinely. Because response
      to treatment is linked to HCV type, this assay could be used to identify HCV
      serotype to guide therapeutic decisions.

PMID- 9580882
TI  - HCV antibodies in saliva and urine.
AB  - Infection with hepatitis C virus (HCV) is usually established by detection of
      serum antibodies (anti-HCV). This study was conducted in order to evaluate
      whether saliva and urine may substitute serum for anti-HCV detection. Serum,
      saliva, and urine were obtained simultaneously from 141 patients with a variety
      of liver diseases and from 52 patients with autoimmune diseases (systemic lupus
      erythematosus n = 27 and rheumatoid arthritis n = 25). The cell free fraction of
      saliva and urine samples was tested for anti-HCV using a modification of a serum
      anti-HCV kit. Western blot analysis was used as a confirmation method. Of the
      patients with liver diseases, 73 were anti-HCV-seropositive. Salivary and urinary
      anti-HCV could be detected in 66 (90%) and 36 (49%) of the anti-HCV-seropositive
      patients, respectively. The presence of anti-HCV in saliva or urine was not
      related to the severity of liver disease. All the anti-HCV-seronegative liver
      patients were negative for salivary anti-HCV and 22 (32%) had urinary anti-HCV.
      The patients with autoimmune diseases were all anti-HCV-seronegative. None had
      detectable salivary anti-HCV while 33 (63%) were positive for urinary anti-HCV.
      Western Blot analysis confirmed the presence of anti-HCV in all serum and saliva
      samples tested but only in 2/12 urine samples. The results suggest that saliva,
      but not urine, may serve as a substitute for serum for the determination of anti
      HCV positivity.

PMID- 9580883
TI  - Isolation and characterization of human monoclonal antibodies against hepatitis C
      virus envelope glycoproteins.
AB  - The isolation and characterization of human monoclonal antibodies (humAbs)
      against the hepatitis C Virus (HCV) glycoproteins E1 and E2 are described. B
      cells from blood donors with anti-HCV were transformed with Epstein-Barr virus.
      The supernatants of the resulting lymphoblastoid clones were screened by ELISA
      with an extract of cells infected with a recombinant vaccinia virus RMPA95
      expressing the envelope proteins E1 and E2 of an HCV genotype 1a virus (H
      strain). Positive clones were fused to the heteromyeloma cell line K6H6/B5.
      Fifteen heterohybridoma cell lines have been established. The specificity of the
      isolated humAbs was determined both by ELISA and Western blot assays. Several
      recombinant extracts expressing either the E1 or E2 protein or truncated forms
      were used in an attempt to map the epitopes on the viral glycoproteins. Some of
      the humAbs were used successfully for immunofluorescence investigation of
      transfected cells. Seven specific anti-E2 humAbs, which react with the envelope
      protein 2 of genotype 1a and 1b isolates, were characterized.

PMID- 9580884
TI  - Clinical and molecular virological differences between fulminant hepatic failures
      following acute and chronic infection with hepatitis B virus.
AB  - Clinical and molecular biological characteristics were compared between patients
      who presented with fulminant hepatic failure following acute infection with
      hepatitis B virus (HBV) and those who developed hepatic failure during they
      carried HBV. The 11 patients with acute HBV infection had higher levels of
      alanine aminotransferase (mean +/- SD: 4943 +/- 2867 vs 1157 +/- 678 IU/L, P <
      0.01), more often with a single peak (91% vs. 0%, P < 0.001), and lower total
      bilirubin level (15.3 +/- 4.4 vs 28.1 +/- 14.3 mg/1000 ml, P < 0.01) than the 13
      patients with chronic HBV infection. Hepatitis B surface antigen was detected
      less often (55% vs. 100%, P < 0.05) and viral DNA polymerase less frequently (0%
      vs. 46%, P < 0.05) in the patients with acute than chronic HBV infection.
      Hepatitis B e antigen was detected in one (9%) patient with acute infection, less
      frequently than in six (46%) patients with chronic infection (P < 0.05).
      Mutations in the precore region was detected in HBV DNA clones from ten (91%)
      patients with acute infection and only in those from eight (62%) patients with
      chronic infection. All HBV DNA clones from the five (38%) patients with chronic
      infection that did not have precore mutations, however, possessed mutations in
      the core promoter. These results indicate that HBV mutants incapable of
      translating hepatitis B e antigen would play a major role in fulminant hepatic
      failure occurring after acute HBV infection. In contrast, HBV variants with core
      promoter mutations for reducing the transcription of hepatitis B e antigen would
      play an additional role in fulminant hepatic failure developing during chronic
      infection.

PMID- 9580885
TI  - G1 phase dependent nuclear localization of relaxed-circular hepatitis B virus DNA
      and aphidicolin-induced accumulation of covalently closed circular DNA.
AB  - During chronic hepatitis B virus (HBV) infection, virus persistence relies on the
      maintenance of a pool of covalently closed circular DNA (cccDNA) in the nuclei of
      infected hepatocytes. To achieve this, HBV DNA has to be transported from the
      cytoplasm to the nucleus. By carrying out subcellular fractionation experiment,
      both of the relaxed-circular (RC) and single-stranded (SS) HBV DNA were found in
      the cytoplasm whereas only RC form could be detected in the nucleus of a
      hepatoblastoma cell line (HepG2) stably producing HBV. This fraction of nuclear
      RC viral DNA was clearly demonstrated in the G1 but not S phase of synchronized
      HepG2 cells. Conversely, the relative amount of cytoplasmic RC viral DNA in the S
      phase was larger than that in the G1 phase. Although no cccDNA could be detected
      in HepG2 cells without synchronization, an increasing amount of cccDNA in the
      nucleus was demonstrated after prolonged incubation of the cells in aphidicolin.
      Finally, by undertaking in situ hybridization using a probe specific to plus
      strand HBV DNA, nuclear viral DNA was detected predominantly in the G1 phase of
      HepG2 cells. In summary, the results indicated that only RC but not SS form of
      HBV DNA was localized to the nuclei of HepG2 cells. The nuclear localization
      occurred preferentially in the G1 but not S phase and prolonged treatment with
      aphidicolin resulted in accumulation of nuclear cccDNA.

PMID- 9580886
TI  - Possible influence of the mutant CCR5 Allele on vertical transmission of HIV-1.
AB  - A possible correlation between the rate of vertical transmission of HIV-1 and the
      presence of the defective HIV co-receptor gene delta 32ccr5 in the chromosomes of
      infants born to HIV-positive mothers was assessed. The prevalence and genotypic
      distribution of the delta 32ccr5 gene were studied in 451 uninfected and 225 HIV
      1-infected adults and 79 children born to HIV-1-positive mothers in Austria (45
      uninfected and 34 infected by vertical transmission). As expected in a Caucasian
      population, the delta 32ccr5 allele was found in uninfected Austrians at a
      frequency of 10% (17.3% heterozygotes and 1.3% delta 32ccr5/ delta 32ccr5
      homozygotes, consistent with the expected Hardy-Weinberg distribution). The
      mutant allele frequency was 11.1% in uninfected children (17.8% heterozygotes,
      2.2% homozygotes) and 9.6% in HIV-positive adults (19.1% heterozygotes but no
      delta 32ccr5/delta 32ccr5 homozygotes). Among the group of 34 vertically infected
      children, however, there were only two heterozygotes and no delta 32ccr5/delta
      32ccr5 homozygotes, corresponding to a significantly reduced mutant allele
      frequency of 2.9% (P = 0.05 compared to HIV-negative children). These results
      suggest that CCR5/delta 32ccr5 heterozygous children are less susceptible to
      vertical transmission of HIV-1. The data also support the hypothesis that delta
      32ccr5 homozygous individuals are resistant to HIV-1 infection.

PMID- 9580887
TI  - Effect of the HIV-1 syncytium-inducing phenotype on disease stage in vertically
      infected children.
AB  - The syncytium-inducing (SI) capability of HIV-1 isolates from 48 HIV-infected
      children was determined in order to examine the association of the SI phenotype
      with an AIDS diagnosis and/or with other clinical parameters in HIV-infected
      children. In a retrospective cross-sectional analysis, phenotypic data were
      linked to clinical and immunologic data from each patient. Multiple longitudinal
      samples were analyzed from 14 patients. Children with SI viruses were older than
      children with nonsyncytium-inducing (NSI) strains. Twelve of 13 children less
      than 2 years old carried NSI viruses, seven of the 12 already had a diagnosis of
      AIDS. Two children under 2 years of age died within 1 month of NSI virus
      isolation. Although plasma p24 antigen levels tended to be higher in the NSI
      group, the difference appeared to reflect high p24 levels in children under 2
      years old with AIDS. When children under 2 were omitted, differences in age, CD4+
      cell counts, p24 antigenemia, and clinical parameters were not significant. The
      SI phenotype of HIV-1 did not occur more frequently in children with an AIDS
      diagnosis. Four children remained stable with SI isolates overtime periods of 16
      to 31 months. Three children's isolates converted from NSI to SI and 2 converted
      from SI to NSI. These data indicate that SI viruses do not play a significant
      role in progression to AIDS during the first 2 years of life. Furthermore, for
      children above the age of 2, the association between advanced disease stage and
      the SI phenotype in adults may not apply.

PMID- 9580888
TI  - Circulating cytomegalic endothelial cells are associated with high human
      cytomegalovirus (HCMV) load in AIDS patients with late-stage disseminated HCMV
      disease.
AB  - The prevalence of circulating cytomegalic endothelial cells, detected currently
      by the pp65-antigenemia assay and described previously in blood of transplanted
      and AIDS patients with disseminated human cytomegalovirus (HCMV) infection, was
      found to be 2.9% in the AIDS population and 6.5% in the fraction of the AIDS
      population with HCMV in blood. Cytomegalic endothelial cells increased to 39.7%
      and 48.4%, respectively, in AIDS patients with very high levels of antigenemia
      and viremia, while an end organ disease reached an incidence of 76.4%. Positive
      and negative predictive values of cytomegalic endothelial cell detection for
      diagnosis of HCMV end organ disease were 73.1% and 21.4% with antigenemia levels
      > 1,000, respectively. On the other hand, in a selected group of 38 cytomegalic
      endothelial cell-positive AIDS patients with < 50 CD4+ T cells/microliter and
      late-stage HCMV disease, who were followed-up for variable periods of time, the
      prevalence of high level antigenemia was 95.3%, that of viremia 86.0% and that of
      L-DNAemia 92.7%, while the incidence of HCMV end organ disease was 84.2%. In this
      population, it was shown that cytomegalic endothelial cell presence was
      associated with lack of (56.0% of episodes) or insufficient (4.0%) anti-HCMV
      treatment or emergence of HCMV drug-resistant strains (17.3%) or short-term
      response to antiviral treatment (22.7%); was determined in the same patient by
      different conditions during follow-up. Longitudinal observations indicated that
      cytomegalic endothelial cells were detected often in blood at least 3 months
      later than end organ disease suggesting that the duration of end organ disease
      was a cofactor associated with the appearance of cytomegalic endothelial cells.

PMID- 9580889
TI  - Glycoprotein B genotype correlates with cell tropism in vivo of human
      cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) strains can be classified into four genotypes of the
      glycoprotein B (gB). In a previous study, the gB genotype 1 was found more
      frequently in bone marrow transplant recipients with nonfatal HCMV infection than
      in patients who died from HCMV disease [Fries et al. (1994): Journal of
      Infectious Diseases 169:769-774]. The distribution and cell tropism of different
      gB types in vivo were investigated. The gB type of HCMV was determined in blood
      or urine specimen from 76 organ and 47 bone marrow transplant recipients using
      PCR and restriction fragment length polymorphism (RFLP). The leukocyte
      populations (polymorphonuclear leukocytes, monocytes, T lymphocytes, non-T
      lymphocytes) of 20 viremic patients were purified by a fluorescence-activated
      cell sorter (FACS) and examined for HCMV infection by PCR. Sequence analysis of
      four randomly selected strains showed that gB types were similar to published
      sequences and no atypical gB types were found. Within the compartments blood and
      urine, the gB types were almost equally distributed, whereas the gB type 1, in
      contrast to gB types 2 and 3, did not infect T lymphocytes in vivo. These data
      show that the gB type correlates with viral tropism in vivo and thus provides
      further evidence that the gB variation may indeed influence the virulence of
      HCMV.

PMID- 9580890
TI  - Altered antibody response to influenza H1N1 vaccine in healthy elderly people as
      determined by HI, ELISA, and neutralization assay.
AB  - To determine the influence of ageing per se as well as of priming histories on
      the antibody response to influenza vaccination, haemagglutination inhibition
      (HI), ELISA IgG, IgA, IgM and neutralizing antibody titres were studied in 43
      healthy young subjects (mean age 23 years) and 55 healthy elderly people (mean
      age 79 years). The HI and ELISA lgG responses to the A/Guizhou/54/89 strain
      (H3N2) for which both the young and the elderly had similar priming histories
      were equal. By contrast, the HI and IgG responses to A/Taiwan/1/86 (H1N1), where
      the priming histories were different, were lower in the elderly (P < 0.05).
      Influenza-specific IgA responses in the elderly tended to be higher for all
      vaccine strains. Influenza-specific postvaccination IgM titres were similar or
      tended to be higher in the elderly. A subgroup of elderly subjects (18%) who did
      not express HI activity to the A/Taiwan/1/86 (H1N1) vaccine strain, reacted in
      the HI assay with the closely related A/Singapore/6/86 (H1N1) strain. These
      elderly people, however, produced lgG antibodies which neutralized A/Taiwan/1/86
      virus in vitro. It is concluded that the elderly are capable of mounting antibody
      responses similar to those observed in the young. Moreover, the observed age
      related differences in antibody responses to H1N1 strains are probably not due to
      ageing of the immune system itself, but are determined by differences in priming
      histories.

PMID- 9580891
TI  - Who is responsible for the science of orthopaedic and sports physical therapy?

PMID- 9580892
TI  - The patient-specific functional scale: validation of its use in persons with neck
      dysfunction.
AB  - Self-report measures of disability are being used more frequently to assess
      patients' outcomes in clinical practice. This study examines the reliability,
      validity, and sensitivity to change of the Patient-Specific Functional Scale when
      applied to persons with neck dysfunction. The Patient-Specific Functional Scale
      and Neck Disability Index were applied at the initial visit, within 72 hours of
      the initial visit, and following 1-4 weeks of treatment in 31 patients with
      cervical dysfunction. At the time of the initial visit, the clinician made an
      estimate of patients' prognoses on a five-point scale. This estimate served as an
      priori construct for change: patients with better ratings would change more. The
      results demonstrate excellent reliability (R = .92) validity (r = .73-.83
      compared with the Neck Disability Index, and r = .52-.64 compared with the
      prognosis rating), and sensitivity of change (r = .79-.83 compared with Neck
      Disability Index change scores, and r = .46-.53 compared with the prognosis
      rating). No difference was found between the Patient-Specific Functional Scale
      and Neck Disability Index in their ability to detect change over time. The
      results of this study are consistent with previous investigations which have
      concluded that the Patient-Specific Functional Scale is an efficient and valid
      measure for assessing disability and change in disability in persons with low
      back pain and knee dysfunction.

PMID- 9580893
TI  - Relationship between hip external rotation and turnout angle for the five
      classical ballet positions.
AB  - Functional turnout for each of the five classical ballet positions involves lower
      extremity motion that occurs primarily through hip external rotation. Ballet
      dancers often attempt to increase turnout angle through excessive motions at the
      foot or knee that may be associated with the development of musculoskeletal
      pathology. The purpose of this study was to further the understanding of turnout
      by identifying the relationship between available hip external rotation an
      functional turnout for the five classical ballet positions. Subjects were 20
      female ballet dancers between the ages of 11 and 14. The investigators measured
      hip external rotation as the sum of passive external rotation available at both
      hips of each subject. Functional turnout angle was measured for each subject as
      the subject stood in each of the five classical ballet positions. A repeated
      measures analysis of variance and Tukey Honestly Significant Difference test
      indicated that hip external rotation was significantly less than functional
      turnout for the five classical ballet positions. No significant differences in
      functional turnout angle were present among the five ballet functional turnout
      angle for each of the five ballet positions. Hip external rotation should not be
      used to predict functional turnout for the five classical ballet positions.
      Turnout in first position may be useful as guide for functional turnout for the
      crossed foot positions: third, fourth, and fifth.

PMID- 9580894
TI  - Reliability and responsiveness of disablement measures following acute ankle
      sprains among athletes.
AB  - The minimum amount of change which represents clinical improvement following
      ankle sprains is unknown. This study considers the usefulness of physiological
      and behavioral measures commonly employed for this purpose in sports
      rehabilitation settings. Thirteen collegiate athletes of both genders were
      measured at approximately 3 and 10 days post-grade I or II ankle sprain.
      Volumetric displacement and sagittal plane ankle range of motion measures were
      used as impairment indicators. Motor ability scores (activity count) and a
      perceived athletic ability measure (visual analog scale) were used to indicate
      functional limitations. Volumetric displacement and both functional limitation
      measures demonstrated responsiveness to change between two occasions of
      measurement separated by 1 week. Observed changes in range of motion deficits
      could not be distinguished from measurement error. The results of this study
      suggest that behavioral measures of motor activity and perceived athletic ability
      may be at least as useful as physical measures of organic dysfunction for
      assessing clinical improvement following acute ankle sprains among athletes.

PMID- 9580895
TI  - The reliability of the star-excursion test in assessing dynamic balance.
AB  - Quantification of dynamic balance is often necessary to assess a patient's level
      of injury or ability to function in order to initiate an appropriate plan of
      care. Some therapists use the star-excursion test in an attempt to quantify
      dynamic balance. This test requires the patient to balance on one leg while
      reaching with the other leg. For the purpose of this study, the reach was
      performed in four directions. No previous researchers have attempted to evaluate
      the reliability of this test. Twenty healthy subjects between the ages of 18 and
      35 years participated in this study. During two testing sessions, each subject
      was required to perform five reaching trials in four directions. Reliability
      estimates, calculated using the intraclass correlation coefficient (2, 1), ranged
      from 0.67 to 0.87. Six duplicate practice sessions were suggested to increase
      this range above 0.86. Task complexity may account for the moderate reliability
      estimates. Subjects should engage in a learning period before being evaluated on
      the star-excursion test.

PMID- 9580896
TI  - Genu recurvatum syndrome.
AB  - Genu recurvatum is a common entity found in the clinic that my have negative
      consequence to knee structures. The purpose of this article is to review the
      anatomy, biomechanics, and clinical effects associated with genu recurvatum. Genu
      recurvatum is operationally defined as knee extension greater than 5 degrees.
      Individuals who exhibit genu recurvatum may experience knee pain, display an
      extension gait pattern, and have poor proprioceptive control of terminal knee
      extension. An evaluative process and treatment program are discussed that include
      muscle imbalance correction, proprioceptive practice, gait, and functional
      training. Taping or knee bracing may be used initially to facilitate knee
      control. This article is intended to draw attention to patients with genu
      recurvatum and presents a suggested treatment progression. Individuals who are
      involved in athletic endeavors should be aware of knee position during activities
      to help protect joint structures.

PMID- 9580897
TI  - Vertical patellar dislocation: a case report.
AB  - The purpose of this case report is to highlight an unusual diagnosis and
      mechanism of injury. Vertical patellar dislocation is an uncommon entity.
      Relatively few cases have been reported in the literature, and most of these have
      occurred in adolescent boys who have sustained a direct blow to the knee while
      engaging in some form of contact sport. The case reported here is a vertical
      patellar dislocation that happened to a 10-year-old girl without any trauma. This
      is an unusual case and seemingly atypical for a vertical patellar dislocation.
      The knowledge of this diagnosis might assist clinicians in the understanding of
      unlikely mechanisms of injury in the assessment and treatment of this
      musculoskeletal disorder.

PMID- 9580898
TI  - In-season management of shoulder pain in a collegiate swimmer: a team approach.
AB  - Shoulder pain is a common problem among competitive swimmers, often limiting
      their ability to train and compete. Although a number of rehabilitation programs
      for shoulder injuries have been reported in the literature, there is a lack of
      objective data regarding the effectiveness of these protocols in the competitive
      swimming population. This case report describes the evaluation and treatment of
      shoulder pain in an NCAA Division I swimmer during the competitive season. Once a
      physical therapy diagnosis was made, a plan of care was developed to address each
      component impairment. This required the input of the team trainers, the team
      physician, and an orthopaedic surgeon. A chief component of the athlete's
      rehabilitation involved allowing the athlete to compete, but not practice.
      Excellent results were achieved, as evidenced by symptom reduction and swimming
      performance. This case report highlights the interactive, team approach necessary
      for optimal management of the injured athlete.

PMID- 9580899
TI  - Are we there yet? When will we be there? Designing collaborative plans for future
      psychiatric rehabilitation nursing practice.

PMID- 9580900
TI  - Promoting the importance of work for persons with psychiatric disabilities--the
      role of the psychiatric nurse.
AB  - 1. Familiarize yourself with the vital resources in your community. 2. Assist
      individuals in focusing on "real life" and practical problem issues. Maintain a
      focus on recovery and rehabilitation issues. 3. Remember: longer-term vocational
      successes depend on individual choice, encouragement, and supports.

PMID- 9580901
TI  - Integrating psychosocial rehabilitation in a community-based faculty nursing
      practice.
AB  - 1. When clients share their experiences with students, the experience helps
      sensitize students to the stigma of mental illness, and also facilitates the
      client's recovery. 2. Encouragement from staff, clinicians, other clients, and
      family members that they can succeed at this next step in what most often
      motivates a client-consumer to "try" something new or "try again". 3. Client
      involvement in community activities is effective in normalizing daily life
      experiences and in breaking down the barrier of stigma.

PMID- 9580902
TI  - Hope: the critical factor in recovery.
AB  - 1. Psychiatric rehabilitation focuses on improving a person's knowledge and
      skills to maximize levels of functioning and developing resources within the
      community to support successful living. 2. The recovery process is a lifelong
      process of defining new possibilities and finding new meaning and purpose in
      life. By accepting the limitations of what they cannot do, clients begin to
      discover what they are able to do and to look forward to a new beginning. 3.
      Facilitating success, connecting to successful role models, managing the illness,
      and educating clients and the community are all identified as areas that enhance
      hope for clients.

PMID- 9580903
TI  - Psychosocial rehabilitation nurses: taking our place on the multidisciplinary
      team.
AB  - Nurses have been working in the AMI/ABLE ISA for the past 6 years as part of a
      multidisciplinary team. The nursing contribution is important to the Team, not
      only because of nursing expertise in providing psychiatric mental health care,
      but also because nurses can provide services unique to nursing, such as health
      assessments and education, and medication support (Fur-long-Norman, Palmer-Erbs,
      & Jonikas, 1997). More than 80 people who are disabled by mental illnesses have
      been served by this innovative program since 1991, and members' hospitalization
      rates have been cut approximately in half by integrating services and reducing
      fragmentation, and by using aggressive outreach and a psychosocial rehabilitation
      approach. Psychosocial rehabilitation nursing has become a subspecialty that has
      expanded the profession. Experience in the AMI/ABLE program demonstrates that
      nurses, as fully integrated members of multidisciplinary teams, adapt to working
      in partnerships with clients and their families, in nontraditional settings.

PMID- 9580904
TI  - To work or not to work: that is not the question.
AB  - 1. Although employers in the public mental health arena may be expected to hire
      consumers of mental health services, it has been much more difficult for people
      with mental disabilities to find work in the private sector, or to return to such
      jobs after an acute episode of mental illness. 2. Many consumer-and survivor-run
      services around the country offer those with mental illness not only volunteer
      and employment opportunities, job training, and placement services, but also good
      role models and hope for the future. 3. How to address gaps in resumes is still
      controversial. However, since it is illegal for employers to ask questions
      designed to elicit information about illness, many experts advise consumers to
      get the job first; they can disclose their illness and ask for reasonable
      accommodations later.

PMID- 9580905
TI  - Tamoxifen and the breast cancer prevention trial: women helping women.

PMID- 9580906
TI  - Screening issues in gynecologic malignancies for women with disabilities:
      critical considerations.
AB  - There are 25 million women with disabilities in the United States. They have
      biologically similar risks to other women for developing all cancers, including
      gynecologic malignancies. Unfortunately, barriers to comparable cancer screening
      include lack of knowledge by women themselves, lack of awareness on the part of
      health care providers about special health concerns clinicians might encounter,
      and physical access barriers. Together, these factors conspire to delay diagnosis
      and treatment of many common gynecologic malignancies. Additionally, medications
      taken by some women with chronic disease states may adversely affect their risk
      for developing certain types of cancer, and they may be at increased risk for
      contracting underdiagnosed sexually transmitted diseases linked to cervical
      cancer. This article describes some important issues regarding incidence and
      screening for gynecologic malignancies in women with disabilities.

PMID- 9580907
TI  - News from the Society for the Advancement of Women's Health Research. Put out
      that light!

PMID- 9580909
TI  - Toward optimal health: the experts respond to hair loss in women. Interview by
      Jodi Godfrey Meisler.

PMID- 9580908
TI  - 1995 assisted reproductive technology success rates: national summary and
      fertility clinic report.
AB  - Although ART offers important options for the treatment of infertility, the
      decision to use ART involves many factors in addition to success rates. Going
      through repeated ART cycles requires substantial commitments of time, effort,
      money, and emotional energy. Couples and individuals considering ART should
      carefully examine all related financial, psychologic, ethical, and medical issues
      before beginning treatment. They should also contact ART clinics to discuss their
      specific medical situation and potential for success using ART. The next
      published report will feature 1996 data and provide a listing of clinics that did
      not submit data. Eventually, the annual report will include information from all
      U.S. fertility clinics, not just those that are SART members.

PMID- 9580910
TI  - All's fair ... but not in diabetes. Women's unique vulnerability: part II.

PMID- 9580911
TI  - Crisis in assisted conception: the British approach to an American dilemma.
AB  - Although British and American couples who are infertile have similar treatment
      options in their home countries, the British system for ensuring quality of care
      has striking advantages over the American status quo in reproductive medicine.
      The British system effectively addresses what continue to be serious problems on
      the American scene, such as the lack of any clear license or certification of
      infertility treatment centers to reassure consumers, the absence of a complete
      consumer-friendly account of success rates at various sites and by technique, and
      the continuing proportional increase in multiple births because of high numbers
      of embryos transferred in in vitro fertilization (IVF) and numbers of oocytes
      produced as a result of ovulation-stimulating drugs. In addition, the British
      system has clear compulsory guidelines in place that regulate what kinds of human
      embryo research can be performed, by whom, and where. In infertility practice,
      the British also have strict controls on the introduction of innovations, such as
      intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis
      (PGD). The British prohibition, for example, against cloning by nuclear
      replacement is already a matter of record, and there is no necessity (as is the
      case in the United States with cloning via nuclear transplantation) to invoke a
      public ban and hope that a private moratorium will be observed. Regardless of
      what one thinks about the clinical and research issues, the clarity and order
      that permeate practice and research in reproductive medicine in Great Britain
      have advantages that could serve as guideposts for necessary reforms in the
      United States.

PMID- 9580912
TI  - The exploitation of autoimmune disease: breast implant litigation and its dire
      implications for women's health.
AB  - Men, women, and children are subject to a number of disease conditions that have
      been documented over many centuries. Among the most recently described and the
      least understood of these conditions are autoimmune diseases. As we unfortunately
      have seen in recent years, the obscure nature of autoimmune disorders has allowed
      scientific distortion by individuals who stand to profit by claiming a cause-and
      effect relationship among some types of autoimmune conditions and a number of
      medical products, resulting in a rapidly expanding use of "junk science" in our
      courtrooms. Attempts have been made recently to implicate a number of
      environmental factors in the development of autoimmune disorders, most notably
      silicone gel-filled breast implants. The controversies surrounding these alleged
      relationships have proved to be among the most contentious, costly, and dangerous
      events ever to occur in women's health care.

PMID- 9580913
TI  - Sense and sensitivity: developing a gender issues perspective in medical
      education.
AB  - As part of a larger project focused on integrating women's health issues and
      gender issues into undergraduate medical education in Canada, the question of
      what is actually meant by a "gender issues perspective" in medical education was
      explored. Clinical experience, discussions with colleagues, and exposure to a
      variety of medical education resources reinforced the complexity of the subject
      and demonstrated the difficulty in making amorphous ideas concrete. Eight
      dimensions encompass the key concepts underlying a gender issues perspective.
      Practical applications highlight the usefulness of these suggested dimensions in
      making sense of and bringing sensitivity to this complex subject.

PMID- 9580914
TI  - Anterior cruciate ligament injuries in the female athlete.
AB  - The normal anterior cruciate ligament (ACL) is critical to knee joint stability,
      especially for athletes in cutting sports. Rupture of the ACL can be a
      devastating, if not career-ending, injury for a young athlete because of the
      resultant instability and increased risk of meniscal and chondral damage.
      Considerably more girls and women than ever before now participate in athletics.
      Some epidemiologic data show that female athletes may sustain a higher incidence
      of ACL injuries than male athletes. Risk factors that may be responsible for
      these increased injury rates are reviewed. History and physical examination are
      most important in establishing the diagnosis of ACL injury, although ancillary
      diagnostic imaging is helpful if the extent of injury is in question. Treatment
      options, including various surgical reconstructions and rehabilitation, are
      discussed, with attention to the specific concerns of the female athlete. With
      appropriate diagnosis and treatment, the ACL-injured athlete may now anticipate
      full return to function and athletic competition.

PMID- 9580915
TI  - Prescription of activity restriction to treat high-risk pregnancies.
AB  - The purpose of this study was to determine by two groups of physicians the use of
      pregnancy bed rest, the types of activity restriction prescribed, if there is
      variability in prescription, and if side effects of this treatment are observed.
      A national survey of 44 directors of maternal fetal medicine (MFM) and a random
      selection of 47 practicing obstetricians certified by the American College of
      Obstetricians and Gynecologists (ACOG) was conducted. The survey contained
      questions about home and hospital bed rest and whether or not side effects of bed
      rest were observed. Physicians were also asked to indicate the type/degree of
      activity restriction prescribed for 16 diagnostic scenarios for women with mild
      hypertension, chronic hypertension, incompetent cervix, preterm labor, premature
      rupture of membranes, placenta previa, and twin pregnancy. Repeated measures
      analysis of variance was used to analyze the type of activity restriction
      prescribed at 20, 24, 28, 32, and 36 weeks' gestation. Results reveal that bed
      rest was prescribed extensively (89%-93%), but few any physical and psychologic
      side effects. Physicians in both groups demonstrated marked variability in
      prescribing the location (home or hospital) and the severity of activity
      restriction even when treating the same condition. MFM directors were
      significantly more likely to treat pregnancy-induced hypertension (p < 0.01) and
      placenta previa with hospital bed rest (p < 0.05). ACOG physicians preferred to
      prescribe either home or hospital bed rest across all diagnostic scenarios,
      whereas the prescription by MFM directors related more to the individual
      diagnosis than to a general preference. Choice of location of bed rest and the
      severity of activity restriction appear to be functions of physicians' practice
      style.

PMID- 9580916
TI  - Sex differences in the factors related to hospital utilization: results from the
      1990 Ontario Health Survey.
AB  - We assessed the factors associated with hospital admission in Ontario, Canada,
      across age-specific and sex-specific groups. Data from the cross-sectional,
      population-based 1990 Ontario Health Survey (OHS) were used to examine the
      relationships between hospital admission and sociodemographic, health care need,
      psychosocial, and lifestyle factors. The OHS sample of 42,698 adults aged > or =
      16 years, weighted to represent more than 7 million Ontarians, was used.
      Hospitalization rates per 1000 in the prior year were 130 for men and 203 for
      women. The higher rates for women are attributed in part to admissions related to
      childbearing. Women who delivered a child in the year before the OHS were
      excluded from subsequent analyses. Multivariate logistic regression models
      revealed that health care need (increasing number of health problems, fair/poor
      health status, older age) was the most important factor associated with higher
      hospitalization rates for men. For women, in addition to health care need,
      psychosocial (low/average well-being) and sociodemographic factors (married, low
      income, unemployed, English/French spoken in the home) were related to higher
      hospital utilization. Health care need is the most important factor for
      describing hospital use in men and women. However, rates of hospital utilization
      for women are more sensitive to sociodemographic factors even in a setting with
      universal health insurance. This suggests that among women, societal factors may
      exist that relate to potential disparities in access to health services. Efforts
      to assess how these factors operate are necessary to aid the development of
      interventions to minimize disparities that may exist.

PMID- 9580917
TI  - Sexual coercion, domestic violence, and negotiating condom use among low-income
      African American women.
AB  - Coercion to engage in unwanted sex places women at risk for human
      immunodeficiency virus (HIV) infection. A survey of 125 women living in low
      income housing developments in Fulton County, Georgia, showed that 53 (42%) women
      had engaged in unwanted sex because a male partner threatened to use force or
      used force to obtain sexual access. Women who had been sexually coerced were more
      likely to have used marijuana and crack cocaine and to have abused alcohol.
      Coerced women were more likely to have been physically abused by a domestic
      partner. These women were also more likely to perceive that requesting male
      partners to use condoms would create a potentially violent situation. These
      results suggest that women experience an interactive constellation of social
      problems that create risks for HIV infection and, therefore, that efforts to
      prevent HIV infection among women will require multifaceted intervention
      strategies to reach both men and women at risk.

PMID- 9580918
TI  - Development and health care needs of lesbians.
AB  - Lesbians have complained about the lack of awareness and sensitivity of their
      health care providers, resulting in unnecessary examinations and inappropriate
      focus on reproductive issues. This study attempted to identify psychosocial and
      health care needs of lesbians, to assess relationships with primary care
      providers and disclosure of sexual orientation, and to describe the chronologic
      features of a sexual identity and lifestyle. An anonymous, self-administered
      written questionnaire was distributed through a campus lesbian organization.
      Fifty-three women (median age 23 years) completed the questionnaire. Whereas 60%
      had disclosed their sexual orientation to their parents, only 31% had "come out"
      to their health care provider. Of participants who had disclosed their sexual
      preference to a provider, 27% reported a negative effect on their health care,
      57% of participants who never had penile intercourse had annual Papanicolaou
      smears, and 16% felt pressured in the past to accept birth control from a
      physician. Lesbian sexuality was associated with several risk factors, such as
      childhood abuse (20%), alcohol or drug problems (39%), suicide attempts (27%),
      depression (49%), and physical or verbal abuse at school (34%). Average age of
      awareness of sexual orientation was 15 years, and average age of first homosexual
      activity was 17 years. Lesbians are at risk for depression, substance abuse, and
      suicide attempts. Although most would like to confide in their physician, few do
      because of fears of negative reactions. Communication must be improved to better
      address their specific health care needs.

PMID- 9580919
TI  - The clinical presentation of tuberculosis.

PMID- 9580920
TI  - Are prognostic factors helpful in determining the indication for pleurodesis in
      malignant pleural effusions?

PMID- 9580921
TI  - Malignant pleural effusion: prognostic factors for survival and response to
      chemical pleurodesis in a series of 120 cases.
AB  - Chemical pleurodesis is an effective treatment of malignant pleural effusions,
      but indications must be individualised to optimise its results. The aim of the
      present study was to investigate the relationship of various prognostic features
      with both the response rate to pleurodesis and the probability of patient
      survival. A non-concurrent cohort study was carried out in which 120 evaluable
      patients with malignant pleural effusion underwent pleurodesis. Lung (40%),
      breast (26.6%), and unknown primary site (12.5%) carcinomas were the most
      frequent neoplasms. Clinical data and pleural fluid parameters were analysed.
      Median overall survival was 9 months. Pleural fluid glucose (< 60 mg/dl),
      Karnofsky performance status (< 70), size of the effusion in chest radiographs
      (massive effusion), pleural fluid pH (< 7.20), presence of concomitant
      alterations in chest radiographs, and pleural lactic acid dehydrogenase levels (>
      600 U/l) showed a significant association with the probability of failure.
      Patients with these features, along with those having non-chemosensitive tumours
      (in particular, non-small cell lung cancer), had a significantly worse actuarial
      survival. This study confirms that some pretreatment clinical data and pleural
      fluid parameters can predict both the outcome of pleurodesis and the survival of
      patients with malignant pleural effusion.

PMID- 9580922
TI  - Bi-level positive airway pressure treatment of obstructive sleep apnoea syndrome.
AB  - We evaluated the effect of non-invasive nocturnal ventilation with the bi-level
      positive airway pressure (BiPAP) ventilator in 12 overweight patients with
      verified obstructive sleep apnoea syndrome (OSAS) and nocturnal hypercapnia. All
      patients exhibited subsequently less overnight CO2 accumulation (p < 0.0001), the
      desaturation event frequency was reduced (p < 0.002), daytime O2 tension rose (p
      < 0.001), daytime CO2 tension was reduced (p < 0.01), and apnoeas were
      eliminated. All symptoms characterising the syndrome, when present at the
      beginning of the therapy, were eliminated during the treatment. Patient
      compliance was high. This study showed that OSAS patients with hypercapnia can be
      effectively treated by BiPAP ventilation during sleep.

PMID- 9580923
TI  - Use of whole-body plethysmography to compare bronchodilator inhaler efficacy.
AB  - Whole-body plethysmography is not included in guidelines from regulatory
      authorities for the development of treatments or delivery devices for lung
      disease, despite its potential advantages compared to spirometry. Two separate
      studies were undertaken to assess the use of specific airway conductance (sGaw)
      as a pharmacodynamic endpoint for the comparison of two bronchodilator delivery
      systems (a novel dry powder inhaler and a standard metered dose inhaler). The
      first pilot study involved delivery of a single dose of salbutamol (200
      micrograms) to 12 healthy volunteers and determination of sGaw up to 120 min
      after treatment. The second study involved delivery of cumulative doses of
      salbutamol (100, 200 and 400 micrograms) to 19 healthy volunteers with
      demonstrated reversibility of sGaw to the bronchodilator and measurement of sGaw
      up to 240 min after treatment. In both studies, increases in sGaw after treatment
      were significant compared to placebo and larger than the recorded increases in
      FEV1. Increases in sGaw were similar for both delivery devices and support the
      therapeutic equivalence of the two products. Power calculations indicated that
      the second study had appropriate statistical power to discriminate between
      treatments. It is concluded that the assessment of sGaw in healthy volunteers may
      be a useful and sensitive pharmacodynamic endpoint for use in the development of
      bronchodilators and their delivery devices.

PMID- 9580924
TI  - Pulmonary function and regional distribution of emphysema as determined by high
      resolution computed tomography.
AB  - In patients with pulmonary emphysema, emphysematous changes are not uniform and
      vary from minimum alveolar destruction to advanced bullous formation, depending
      on the lobe or site in the lungs. However, we have little knowledge on whether or
      how this nonuniformity or localization affects pulmonary function in PE patients.
      Therefore, we measured the computed tomography (CT) density of divided sites in
      lungs with high-resolution CT images from 25 PE patients (FEV1.0%, mean +/- SD 36
      +/- 9%, %DLCO 48 +/- 16%, all men, 68 +/- 4 years) and compared them to various
      parameters of pulmonary function. The mean CT density of whole lungs correlated
      with 12 pulmonary function parameters including FEV1.0 and diffusion capacity.
      When both lung fields were divided into peripheral, intermediate and central
      portions, the CT density of the central portion correlated with all pulmonary
      function parameters with which CT density of whole lungs correlated. In contrast,
      the CT density of the peripheral portion significantly correlated with only 7
      parameters with smaller correlation coefficient values than those of the central
      portion. When divided into upper, middle and lower portions, the CT densities of
      upper, middle and lower portions correlated with 6, 8 and 10 of the 12 pulmonary
      function parameters which correlated with the density of whole lungs,
      respectively. The delta value of CT densities between the upper and lower
      portions or between the lateral and medial portions correlated with obstructive
      impairment (FEV1.0 and FEV1.0%). These findings suggest that (1) central rather
      than peripheral emphysematous changes affect pulmonary function, and (2)
      uniformity of emphysematous change correlates with the severity of airway
      obstruction in PE patients.

PMID- 9580925
TI  - Influence of asthma in pregnancy on labor and the newborn.
AB  - Asthma in pregnancy has been associated with maternal and fetal morbidity and
      mortality. This study examines the relations of asthma in pregnancy, its severity
      and its treatment to the labor process, maternal and fetal parameters. Hundred
      and one consecutive asthmatic women, who gave birth to single babies between
      November 1993 and November 1994 at the Soroka Medical Center were studied. A
      group of 77 nonasthmatic women, matched for age and ethnic origin, who gave birth
      to single babies during the same period served as controls. A larger percentage
      of asthmatic women suffered from respiratory and urinary tract infections than in
      the control group (p < 0.001). Severe asthma was associated with a higher rate of
      infections than milder asthma (p = 0.01). The incidence of smoking was higher
      among asthmatic women than among controls (p = 0.037). No association was found
      between socioeconomic status and smoking or infections. No association was found
      between maternal asthma or maternal use of corticosteroids and the following:
      maternal hypertension, maternal diabetes, low birth weight (< 2,500 g), preterm
      delivery (< 37 weeks), adequacy of weight to gestational age and Apgar scores.
      Three infants with congenital heart defects were born to asthmatic mothers. When
      the presentation of the fetus was not cephalic, all the asthmatic women were
      delivered by cesarean section, versus only 60% in the control group (p = 0.08).
      Labor was induced with oxytocin more often in the asthma group than in the
      control group (p = 0.07). We conclude that the labor and neonatal outcome in
      pregnant asthmatic women treated medically is good, even when asthma is severe
      and when the patient is treated with corticosteroids. There is, however, a
      relation between asthma in pregnancy, especially if severe, and predisposition to
      infections.

PMID- 9580926
TI  - Surfactant function in neonates with respiratory distress syndrome.
AB  - The function of pulmonary surfactant of a group of 14 preterm neonates (birth
      weight 907 +/- 60 g) who suffered from severe respiratory distress syndrome (RDS)
      and who had received exogenous bovine lipid extracted surfactant on the first day
      of life was compared to that in a second group of 8 neonates (birth weight 940 +/
      110 g) with mild RDS who had not received surfactant treatment. Mechanical
      respiratory support from day 2 on was the same in both groups. The minimal
      surface tension (gamma(min)) improved steadily, falling from about 30 mN/m
      initially to less than 20 mN/m before extubation. A consistent but loose
      correlation was found between gamma(min) and mechanical respiratory support
      necessary, as quantitated by the oxygenation index. Total protein was about 0.8
      +/- 0.2 mg/mg of phospholipids and did not change during the first week of life.
      There were no correlations between total protein and gamma(min) or the
      oxygenation index. The data suggest that inhibition of surfactant function by
      proteins leaked into the airspaces does not play a major role during recovery
      from RDS. Instead, endogenous remodelling of surfactant might be of greater
      relevance.

PMID- 9580927
TI  - Water-soluble cooling lubricants induce airway hyperresponsiveness in rabbits.
AB  - Airway hyperresponsiveness (AHR) to water-soluble cooling lubricants (CL) induced
      by aerosol administered by tracheal tube was studied in a rabbit model of
      occupational lung disease. Two commercial CL were examined: the first was of the
      boric acid amine ester type without biozide (CL-BAE), the second was of the
      sulfonate type with biozide (CL-SB). 50, 5.0 or 0.5 mg/m3 CL was administered
      over a period of twice 2 h to six different groups of rabbits. Airway
      responsiveness (AR) to aerosols of 0.2% and 2.0% acetylcholine solution (ACH) was
      measured before and after each exposure to CL. A control group A of nine animals
      not exposed to CL showed no significant respiratory responses following
      inhalation of 0.2% ACH for 1 min. Conversely, inhalation of 2.0% ACH almost
      doubled the dynamic elastance (Edyn) in the ACH challenge test in this animal
      group. Airway resistance (RI), Edyn, slope of inspiratory pressure generation
      (delta Pes/tI), arterial pressure (Pa) and arterial blood gas tensions (PaO2,
      PaCO2) were not significantly altered during and after exposures to CL. However,
      after CL-BAE inhalation of 50 and 5 mg/m3 over 4 h, the amplitude of the ACH
      induced airway obstruction indicated by the changes in Edyn rose significantly to
      almost five times the control response before exposure (group C, D, p < 0.005).
      Similar changes in RI and delta Pes/tI were obtained. After inhalation of 0.5
      mg/m3 CL-BAE (group D), no significant changes in AR were observed. Similar to CL
      BAE inhalation of 50 mg/m3, CL-SB caused enlarged AR in the ACH challenge test
      (group E), whereas no significant changes were found after exposure to 5.0 and
      0.5 mg/m3 in groups F and G. In summary, CL aerosols with and without biozide in
      the range of 50 and 5 mg/m3 applied via tracheal tubes increased AR to ACH within
      4 h of exposure in a time- and concentration-dependent manner. It has to be
      assumed that this augmented AR indicates an increased risk of developing
      lubricant-induced obstructive lung diseases.

PMID- 9580928
TI  - Pneumothorax or the end of a wire's journey.

PMID- 9580929
TI  - Paradoxical pleural response to antituberculous chemotherapy and isoniazid
      induced lupus. Review and report of two cases.
AB  - Among 28 inpatients receiving antituberculous chemotherapies including isoniazid
      (INH) and rifampicin, we found 2 patients with newly developing pleural effusion
      in the hemithorax during the initial phase of successful chemotherapy. The
      analysis of the effusion fluids revealed an elevated level of antinuclear
      antibody and a decreased level of total component, which are findings compatible
      with lupus pleuritis. The peripheral lymphocyte stimulation test using INH was
      positive in 1 patient. To the best of our knowledge, there has been no published
      discussion of the relationship between a paradoxical response to antituberculous
      treatment and INH-induced lupus.

PMID- 9580930
TI  - Anaplastic large cell lymphoma presenting as an endobronchial polypoid mass.
AB  - We present a case of CD30+ anaplastic large cell lymphoma (ALCL) with a unusual
      endobronchial polypoid mass. There was para-aortic lymphadenopathy on the CT
      scan. This case illustrates that ALCL should be included in the differential
      diagnosis of endobronchial mass lesions.

PMID- 9580931
TI  - An exotic cause of chronic cough.

PMID- 9580932
TI  - Palliative care: past, present, and future perspectives.
AB  - OBJECTIVES: To provide a review of the development and impact of palliative care;
      to discuss quality of lie as a framework for guiding clinical practice and
      research in palliative care; and to identify future trends that are likely to
      affect palliative care services. DATA SOURCES: Research studies, review articles,
      and book chapters. CONCLUSIONS: Palliative care is in the process of dynamic
      change. Advocates of palliative care are suggesting that cost-effective holistic
      care strategies should be available to patients and families throughout the
      illness trajectory, not just reserved for end of life care. IMPLICATIONS FOR
      NURSING PRACTICE: Incorporation of palliative care principles across the cancer
      illness trajectory requires an attitude shift by all members of the
      multidisciplinary team.

PMID- 9580934
TI  - Psychosocial aspects of palliative care.
AB  - OBJECTIVES: To provide information about factors that affect psychosocial
      adjustment among individuals and families who are faced with chronic illness; to
      discuss assessment guidelines and risk factors that may indicate a need for
      professional intervention; and to review psychosocial interventions that are used
      to minimized distress and promote adaptation. DATA SOURCES: Research studies,
      review articles, and book chapters. CONCLUSIONS: The majority of cancer patients
      experience emotional turmoil that occurs at transition points along the illness
      trajectory. Psychosocial issues faced by patients and their families are
      influenced by individual, sociocultural, medical, and family factors.
      IMPLICATIONS FOR NURSING PRACTICE: Supportive psychotherapeutic measures help to
      minimize distress, enhance feelings of control, and improve quality of life.

PMID- 9580933
TI  - Promoting symptom control in palliative care.
AB  - OBJECTIVES: To describe management of common physical problems that occur in
      patients with advanced cancer. DATA SOURCES: Research and review articles, book
      chapters, and published guidelines. CONCLUSIONS: Effective symptom control for
      patients with advanced cancer requires the coordinated efforts of a
      multidisciplinary team. Excellent palliation can be achieved in patients
      suffering from pain, as well as from gastrointestinal, respiratory, or
      dermatologic disorders. IMPLICATIONS FOR NURSING PRACTICE: Nursing is the
      cornerstone of effective palliative care. Through accurate assessments and
      expertise in delivering pharmacologic and nonpharmacologic treatments, nurses
      ensure optimal palliation of physical symptoms.

PMID- 9580935
TI  - The spiritual dimension of palliative care.
AB  - OBJECTIVES: To review the relevant literature about spirituality and palliation
      in oncology and to suggest a model for framing and understanding the spiritual
      themes oncology patients may present. DATA SOURCES: Research studies, review
      articles, and books related to spirituality, palliation, patient and staff
      preferences, family therapy, and culture. CONCLUSIONS: Spirituality/religion is a
      significant element in the lives of most Americans and plays a role in coping
      with crisis events such as cancer. Responding to the spiritual dimension is an
      important part of palliative care. IMPLICATIONS FOR NURSING PRACTICE: Caregivers
      must learn and use appropriate assessment protocols and include appropriate
      spiritual/religious interventions in careplans.

PMID- 9580936
TI  - Promoting patient decision making in life-and-death situations.
AB  - OBJECTIVES: To review factors in the health care culture that deny seriously ill
      patients' last wishes regarding care. DATA SOURCES: Review articles and research
      studies that pertain to decision making. CONCLUSIONS: Decision making in
      palliative care has been identified as an understudied area. Although there are
      significant benefits to being involved in treatment decision making, long-term
      follow-up of the consequences of active participation in the final stages of life
      is lacking. IMPLICATIONS FOR NURSING PRACTICE: Nurses have a role to play in
      assisting patients and their families in treatment decision making in both the
      curative and palliative phase of care. A nursing intervention to promote patient
      involvement in decision making is described.

PMID- 9580937
TI  - Unraveling ethical issues in palliative care.
AB  - OBJECTIVES: To describe the ethical issues inherent in palliative care and the
      essential role of nurses in addressing the ethical dimensions of professional
      practice. DATA SOURCE: Review articles, research studies, and books related to
      ethical issues in palliative care. CONCLUSIONS: Nurses in all roles and practice
      settings confront numerous ethical concerns. Some of the most perplexing and
      troubling ethical issues arise within the context of palliative care. Being
      prepared to deal with these ethical issues can foster patient and family well
      being and protect the integrity of the nurse. IMPLICATIONS FOR NURSING PRACTICE:
      Oncology nurses have a vital role in improving the quality of end-of-life care.
      Attention to the ethical dimension of palliative care is necessary to
      accomplishing this.

PMID- 9580938
TI  - Loss, grief, and bereavement in family members of cancer patients.
AB  - OBJECTIVES: To review loss, grief, and bereavement related to family caregivers
      of cancer patients during illness and after death, and to review interventions to
      enhance survivors' recovery after the patient's death. DATA SOURCES: Review
      articles, research studies, book chapters, and data from authors' research.
      CONCLUSIONS: Loss and grief can lead to positive outcomes in survivors of
      patients who have died of cancer. Conversely, negative bereavement outcomes may
      put survivors at risk for illness and even death. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses can provide interventions for family members that may positively
      influence physical health as well as recovery from bereavement. Outcomes research
      is needed to expand our understanding about how interventions affect survivors'
      recovery from bereavement.

PMID- 9580939
TI  - Caring for the caregiver in oncology and palliative care.
AB  - OBJECTIVES: To review the stressors and manifestations of stress present in
      oncology and palliative care settings and elucidate successful coping strategies.
      DATA SOURCES: Review articles and research reports. CONCLUSIONS: Professional
      care of advanced cancer patients and their families confronts nurses with a
      variety of challenges and stressors. Multiple strategies have been described in
      the literature to assist professionals to cope with stressful aspects of clinical
      practice. Research is needed to test the efficacy of these strategies.
      IMPLICATIONS FOR NURSING PRACTICE: Personal coping strategies and the development
      of supportive collaborative relationships within the work environment are
      essential to the enhancement of self-esteem and professional effectiveness.

PMID- 9580940
TI  - Regulatory barriers to pain management.
AB  - OBJECTIVES: To provide an overview of relevant federal and state policies, as
      well as recommendations for identifying and addressing barriers to the treatment
      of cancer and non-cancer pain. DATA SOURCES: Review of federal and state statutes
      and medical board guidelines. CONCLUSIONS: There has been an increase in pain
      related policies since the mid 1980s, with recent years showing a significant
      amount of policy development and adoption. However, a variety of laws and
      policies contain provisions that have the potential to discourage the use of
      opioid analgesics for the relief of pain. IMPLICATIONS FOR NURSING PRACTICE: The
      evaluation and treatment of patients with cancer and non-cancer pain can be
      enhanced by a knowledge of the specific restrictions of controlled substances
      statutes and practice guidelines. In this way, there will be less chance for
      nurses to practice outside established legal parameters.

PMID- 9580941
TI  - Cost-effectiveness and palliative care.
AB  - OBJECTIVES: To examine the issues and methods in measuring the cost-effectiveness
      of palliative care for incurable cancer. DATA SOURCES: Review articles, book
      chapters, and research studies pertaining to cost-effectiveness and palliative
      care. CONCLUSIONS: All health care interventions, whether palliative or active
      therapy, are delivered at a price. Assessing the cost-effectiveness of
      interventions does not mean that less is better; it means that whatever is spent
      maximizes the utility of resource allocation. IMPLICATIONS FOR NURSING PRACTICE:
      Nurses influence both the cost and the effectiveness of palliative care. Cost of
      nursing services is often factored into the numerator of the cost-effective
      equation. Effectiveness of nursing care should be factored into the denominator
      and can be measured in multiple ways, including the impact on patients' quality
      of life. Nurses can play an active role in assessing and advocating for the cost
      effectiveness of palliative interventions.

PMID- 9580942
TI  - Control of the luteal function in humans.
AB  - Although luteinizing hormone (LH) of the anterior pituitary is considered
      primarily responsible for the initiation of luteinization in most species, the
      mechanisms governing the subsequent life and death of the corpus luteum vary
      among species. In women and in nonhuman primate, the corpus luteum derives its
      support from LH that must be continuously present. To date, the factors
      regulating the life span and endocrine activity of the corpus luteum in humans
      and primates are not completely understood. This article summarizes our study on
      luteinizing hormone and chorionic gonadotropin receptors in human corpora lutea
      during the menstrual cycle and pregnancy and the apoptosis of human corpora lutea
      during the menstrual cycle and pregnancy.

PMID- 9580944
TI  - Autocrine/paracrine regulation of normal human corpus luteum development.
AB  - The human corpus luteum (CL) is a transient endocrine gland regulated primarily
      by the age-dependent action of LH/hCG, which initiates a series of cell-specific
      processes necessary for the structure and also function of the gland. An
      extensive local regulation of the luteal function also exists, based on the
      heterogeneity of the cellular composition of the CL. It is most likely that
      interactions occur among the different subpopulations of steroidogenic (large and
      small luteal cells) and nonsteroidogenic cells (leukocytes, endothelial cells,
      and fibroblasts). Therefore, local produced substances, including steroids,
      growth factors, reactive oxygen species, and, recently, nitric oxide, may
      modulate luteal life span. The knowledge of the basic events involved in the
      control of human luteal function may lead to a better understanding of the
      physiopathology of the human menstrual cycle.

PMID- 9580943
TI  - Localization of steroidogenesis and steroid receptors in human corpus luteum.
      Classification of human corpus luteum (CL) into estrogen-producing degenerating
      CL, and nonsteroid-producing degenerating CL.
AB  - In the analysis of the regulation of human corpus luteum, it is very important to
      localize the sites of specific steroid hormone production to obtain a better
      understanding of luteal function. We have examined expression of steroidogenic
      enzymes, steroid receptors, and adrenal 4 binding protein (Ad4BP), a
      transcription factor of steroidogenesis, in corpus luteum of normal cycling human
      ovary. Corpus luteum can be classified into four different stages from ovulation
      to complete regression or fibrosis based on these findings: (1) corpus luteum,
      (2) steroid-producing degenerating corpus luteum or SPDCL, (3) nonsteroid
      producing or NSPDCL, and (4) corpus albicans. Corpus luteum in the luteal phase
      is characterized as follows: (a) the expression of P450scc (cholesterol side
      chain cleavage), 3 beta HSD (hydroxysteroid dehydrogenase), and Ad4BP in almost
      all the luteinized granulosa and theca cells, consistent with active progesterone
      biosynthesis; (b) expression of estrogen-producing P450arom (aromatase) in
      luteinized granulosa cells, indicating active estrogen production and that of
      P450c17 (17 alpha hydroxylase) in luteinized theca cells, and (c) expression of
      progesterone receptor (PR) and androgen receptor (AR) in both luteinized
      granulosa and theca cells. SPDCL correspond to corpus luteum undergoing
      regression or degeneration in the following cycle and are characterized as
      follows: (a) absence of all the steroidogenic enzymes and Ad4BP in the luteinized
      granulosa cells, suggestive of hormonally inactive nature of these cells and (b)
      marked expression of P450scc, 3 beta HSD, P450c17 and Ad4BP in luteinized theca
      cells. NSPDCL is characterized as the absence of all the steroidogenic enzymes
      and sporadic expression of Ad4BP in luteinized theca cells. These findings
      indicate that luteal cells remain even after losing expression of steroidogenic
      enzymes, consistent with a prolonged process of degeneration or regression of
      human corpus luteum. In corpus albicans, all the cells were replaced by fibrosis
      and steroidogenic enzymes; steroid receptors and Ad4BP were not expressed at all.
      Localization of steroidogenesis in human corpus luteum has thus provided new
      insights into understanding of its biological features.

PMID- 9580945
TI  - Immune regulation of corpus luteum function.
AB  - Immune cells of myeloid and lymphoid lineages constitute a significant cell mass
      in the corpus luteum. Changes in the distribution and numbers of these cells
      within the corpus luteum take place during the life span of the corpus luteum.
      These cells are now recognized to be important both in structural changes of the
      corpus luteum as well as in the regulation of steroidogenesis. Cytokines are
      secreted from immune cells and other cells of the corpus luteum and comprise an
      important component of the intercellular signaling that is regulating tissue
      remodeling and the endocrine activity of the gland. This review covers recent
      findings of the participation of immune cells and cytokines in the regulation of
      the corpus luteum function.

PMID- 9580946
TI  - Role of endothelial cells in the steroidogenic activity of the bovine corpus
      luteum.
AB  - The LH surge triggers the ovulation of the preovulatory follicle and subsequent
      formation of a corpus luteum. After ovulation, microvessels from the thecal layer
      grow into the granulosa cell layer and a rapid process of neovascularization
      takes place, by midcycle endothelial cells constitute more than 50% of total
      corpus luteum (CL) cells. Concomitantly with the angiogenic process, luteal
      steroidogenic cells differentiate as they are surrounded by the growing capillary
      network. Luteal regression, on the other hand, is accompanied by changes in blood
      flow and vasculature. Thus, changes in the endothelial cell population within the
      CL closely consort with the functional changes occurring during various stages of
      the CL life span. This article summarizes data demonstrating that endothelial
      cells play an essential role in luteal steroidogenic activity by being involved
      in both luteotrophic and luteolytic processes.

PMID- 9580947
TI  - Cellular interactions in the corpus luteum.
AB  - The corpus luteum (CL) is an organ that exhibits extremely rapid growth,
      development, and regression during the course of each nonpregnant cycle. The CL
      consists of steroidogenic (parenchymal) and nonsteroidogenic (nonparenchymal)
      cells. The small and large parenchymal cells differ in numerous morphological and
      functional characteristics, and are thought to interact with each other to
      maintain normal luteal function. These steroidogenic luteal cells also interact
      with the nonsteroidogenic cells; for example, they produce factors that stimulate
      proliferation and migration of endothelial cells and proliferation of
      fibroblasts; they also may enhance or suppress immune cell function. Conversely,
      endothelial cells produce factors that modulate steroidogenesis, and immune cells
      produce cytokines that modify the secretory function of steroidogenic cells.
      Cellular interactions may be mediated by several mechanisms, including humoral
      (endocrine and paracrine) pathways as well as contact-dependent (gap junctional)
      pathways. Thus, hormones, growth factors and cytokines produced locally by
      steroidogenic or nonsteroidogenic cells may be transferred from cell to cell
      indirectly or directly to regulate luteal function. Gap junctions are present in
      luteal tissues of several species, and gap junctional intercellular communication
      is affected by the stage of luteal development and systemic and local regulators
      of luteal function. Such cellular interactions probably are important in luteal
      hormone production, signal transduction, angiogenesis, and luteolysis because of
      their role in coordinating function among the various luteal cell types.

PMID- 9580948
TI  - Oxytocin in intercellular communication in the corpus luteum.
AB  - Although oxytocin has been recognized as a product of the corpus luteum in
      numerous species, including nonhuman primate and women, for sometime, its precise
      role in luteal physiology has remained obscure. However, with the recent
      observations that the steroidogenic activity of the large and small cells is
      increased in the presence of LH when these cells are in intimate contact has led
      to the hypothesis that cell-to-cell communication must occur between these cells.
      Cell-to-cell communication is possible via several mechanisms, including
      paracrine/autocrine and intercellular crosstalk via gap junctions. Substantial
      morphological and immunohistological evidence using antibodies to gap-junction
      specific proteins, the connexins, indicates the presence of gap junctions in
      corpora lutea. Our recent studies indicate that oxytocin affects the expression
      of the gap-junction protein connexin-43 and that the gonadotropins are intimately
      involved in this action. The synthesis of oxytocin and the oxytocin receptor is
      influenced by the gonadotropins and locally produced prostaglandins. Oxytocin
      stimulates estradiol synthesis, which may affect the expression of the gap
      junction protein connexin-43, allowing interaction between the large cells and
      small cells of the corpus luteum. With the ubiquitous presence of oxytocin and
      its receptor, and the presence of gap junctions in the corpora lutea of numerous
      species, it is concluded that oxytocin is involved in not only
      paracrine/autocrine interaction but also may be of significant importance in
      intercellular crosstalk in the corpus luteum.

PMID- 9580949
TI  - The role of steroidogenic and nonsteroidogenic luteal cell interactions in
      regulating progesterone production.
AB  - The corpus luteum is an extremely important reproductive endocrine gland that
      influences numerous physiological processes and is therefore perhaps the most
      widely studied reproductive endocrine structure to date. The corpus luteum and
      its major product, progesterone, are central to any discussion of impaired
      reproductive performance. It is generally agreed that our best chances for
      reducing reproductive losses lie in a thorough understanding of the mechanisms
      controlling luteal function during reproductive cycles and pregnancy. Normal
      corpus luteum function is dependent on numerous regulatory factors, such as
      prostaglandins, oxytocin, steroids, growth factors, cytokines, etc. Recently,
      increased interest in studying luteal cell interactions (steroidogenic large and
      small luteal cells as well as nonsteroidogenic "accessory" cells of the corpus
      luteum) has produced new evidence of communication within the corpus luteum that
      influences its function. The exact means of communication among the luteal cells
      are not known; however, this interaction seems to involve both luteotropic and
      luteolytic actions and can occur through either contact-dependent and contact
      independent mechanisms.

PMID- 9580950
TI  - Changes in proteoglycans of intervertebral disc in diabetic patients. A possible
      cause of increased back pain.
AB  - STUDY DESIGN: Characterization of the analytic profile of proteoglycans in the
      intervertebral discs at L4-L5 of nondiabetic (n = 5) and diabetic (n = 5) age
      matched subjects. The discs used were discarded material from operations.
      OBJECTIVES: To clarify the reason for the higher risk of disc prolapse in
      diabetic patients. SUMMARY OF BACKGROUND DATA: The pathogenesis of diabetes
      results from a combination of neurologic dysfunctions and a yet undefined
      metabolic failure, which leads to an abnormal proteoglycan profile. METHODS: The
      following methods were used to determine the proteoglycan profile: the
      measurement of 35S-sulfate uptake per gram wet tissue into sulfated
      glycosaminoglycan using fresh tissue explants; extraction of proteoglycans by 4 M
      guanidinium chloride containing protease inhibitors, with further purification by
      ultracentrifugation on cesium chloride buoyant density gradient under
      dissociative conditions; total uronic acid and protein contents in the various
      gradient fractions; assessing the length of sugar side chains of isolated
      35Sulfate-glycosaminoglycan molecules by separation of the glycosaminoglycan
      molecules on a Sepharose 6B-CL column; and paper chromatography of the final
      digest products of glycosaminoglycan molecules obtained by chondroitinase ABC, a
      glycosaminoglycan-degrading enzyme. RESULTS: The findings show that discs from
      normal nondiabetic subjects have 15 times the rate of 35Sulfate incorporation
      into glycosaminoglycan molecules than do discs of diabetic patients. The
      proteoglycans of diabetic patients are banded at a lower buoyant density,
      indicating a lowered glycosylation rate and a lower number of sugar side chains
      per core protein. In discs of diabetic patients, there is a slight increase in
      the chain length of chondroitin sulfate. Further analysis of the
      glycosaminoglycan chains showed a decreased amount of keratan sulfate, compared
      with that in nondiabetic subjects. However, the total uronic acid content of the
      disc tissues and the ratio of uronic acid to protein of each fraction were
      unchanged in diabetic patients versus that in control subjects. CONCLUSIONS:
      Discs in patients with diabetes have proteoglycans with lower buoyant density and
      substantially undersulfated glycosaminoglycan, which with the specific neurologic
      damage in these patients, might lead to increased susceptibility to disc
      prolapse.

PMID- 9580951
TI  - Correlation between bone mineral density and intervertebral disc degeneration.
AB  - STUDY DESIGN: Intervertebral disc area, disc bulge ratio, and bone mineral
      density were measured in 86 postmenopausal women and the data analyzed.
      OBJECTIVE: To examine quantitatively the correlation between intervertebral disc
      degeneration and bone mass. SUMMARY OF BACKGROUND DATA: In results of previous
      studies, an inverse correlation between osteoporosis and spondylosis has been
      reported. In these studies, only radiographic findings were used to evaluate
      spondylosis; changes in the intervertebral disc itself were not investigated.
      METHODS: To determine bone mass, total-body bone mineral density, lumbar bone
      mineral density, and age-matched control values of bone mineral density were
      measured by dual-energy X-ray absorptiometry in all cases. To evaluate
      intervertebral disc degeneration, disc area and disc bulge ratio (calculated by
      measuring the areas protruding from lines connecting the middle points of the
      anterior and posterior borders of the vertebral bodies) were obtained from four
      discs, using magnetic resonance images of the lumbar spine. The correlation
      between bone mass data and disc area data was analyzed. RESULTS: Bone mineral
      density showed a significant decrease with increasing age. Disc area and disc
      bulge ratio had no relation to age. There was a negative correlation between
      total-body bone mineral density, lumbar bone mineral density, and age-matched
      control values versus disc area, and a positive correlation between all bone
      mineral density data and the disc bulge ratio. CONCLUSIONS: According to the
      results of the analysis by disc morphology and bone mass, especially total body
      bone mineral density, bone mass has an inverse correlation to intervertebral disc
      degeneration--i.e., reduction and disc bulge--which is important when considering
      degenerative spinal diseases and osteoporosis.

PMID- 9580952
TI  - The involvement of matrix metalloproteinases and inflammation in lumbar disc
      herniation.
AB  - STUDY DESIGN: Surgically obtained herniated lumbar disc specimens were stained
      with hematoxylin-eosin or toluidine blue (for detection of proteoglycans) or were
      immunostained with monoclonal antibodies (CD68), antihuman interstitial
      collagenase (matrix metalloproteinase [MMP]-1) and antihuman stromelysin (MMP-3).
      OBJECTIVE: To investigate the possible correlation of matrix metalloproteinase
      activity to granulation tissue formation and lumbar disc herniation, depending on
      the type of herniation. SUMMARY OF BACKGROUND DATA: Interstitial collagenase and
      stromelysin have been implicated in the degradation of the matrix of articular
      cartilage in rheumatoid arthritis, osteoarthritis and degenerated disc tissues.
      However, their role in the herniation of the intervertebral disc has received
      little study. METHODS: Twenty-one specimens of lumbar disc herniation (classified
      as protrusions, subligamentous extrusions, transligamentous extrusions, and
      sequestrations) and four nonherniated discs were stained with hematoxylin-eosin
      or toluidine blue or were immunostained with monoclonal antibodies to CD20,
      CD45RO, and CD68, anti-MMP-1, and anti-MMP-3, using the avidin-biotin-peroxidase
      complex method. The amount of granulation tissue and results of staining were
      graded to examine differences in histology among the four herniation types.
      RESULTS: In sequestration and transligamentous extrusion specimens, granulation
      tissue containing many CD68-positive macrophages was commonly observed. Most
      cells in granulation tissue, as well as chondrocytes, stained positively with
      anti-MMP-1 and anti-MMP-3 antibodies. Granulation tissue was less commonly
      observed in subligamentous extrusions and was absent from most protrusion
      specimens and all nonherniated specimens. B and T lymphocytes could not be
      demonstrated in granulation tissue. CONCLUSIONS: The increased staining of MMP-1
      and MMP-3 associated with inflammatory cells of granulation tissue in herniated
      discs suggests a causal correlation of these proteinases to tissue degradation in
      herniation.

PMID- 9580953
TI  - Effects of steroid and lipopolysaccharide on spontaneous resorption of herniated
      intervertebral discs. An experimental study in the rabbit.
AB  - STUDY DESIGN: Histologic examination was performed on autografted intervertebral
      disc materials of rabbit models, which were partially incised through a
      retroperitoneal approach at L1-L2 and grafted within the posterior epidural space
      at L4. OBJECTIVE: To evaluate whether the resorption process of the herniated
      intervertebral disc is influenced and controlled by treatments with medications.
      SUMMARY OF BACKGROUND DATA: Regarding resorption of herniated intervertebral
      discs, recent studies of magnetic resonance images and histologic investigations
      of surgically resected specimens in lumber disc herniation patients have been
      reported. It has been shown that inflammatory factors may play an important role
      in the mechanism of resorption of the herniated intervertebral disc. However,
      little is known about the origin of newly formed vessels and inflammatory cells
      detected in herniated disc specimens from patients. In this study, The resorption
      process of disc material grafted into the epidural space was observed in a rabbit
      model. METHODS: Thirty-six adult rabbits were used. The L1-L2 intervertebral disc
      was partially incised through a retroperitoneal approach. The harvested disc
      material, which contains the nucleus pulposus and the anulus fibrosus were placed
      into the posterior epidural space at L4 of the same rabbit. The animals were
      divided into control, and steroid groups. The control group received no treatment
      after surgery. In the lipopolysaccharide group, rabbits were injected 1 mg/kg
      into the peritoneum immediately and at 7 days after surgery. In the steroid
      group, rabbits were injected with 1 mg/kg betamethasone into the epidural space
      daily from 1 to 7 days after surgery. Rabbits of each group were killed for
      histologic examination at 1, 2, 4, and 8 weeks after surgery. RESULTS: At 1 and 2
      weeks after surgery, inflammatory cells and newly formed vessels were more
      frequently observed in the lipopolysaccharide group than in the control and
      steroid groups. At 4 weeks after surgery, derangement and loosening of collagen
      fibers were also observed in the lipopolysaccharide group. At 8 weeks after
      surgery, fragmentation and partial disappearance of matrix were observed in the
      control and lipopolysaccharide groups. Most of the intervertebral discs were
      replaced by fibrous tissues in the lipopolysaccharide group. However, the matrix
      of the intervertebral disc almost remained. CONCLUSIONS: Autologous
      intervertebral disc material grafted into the epidural space was penetrated by
      newly formed vessels produced from the epidural fat tissue and resolved as the
      result of inflammatory reaction. Lipopolysaccharide accelerated the replacement
      of grafted intervertebral disc by fibrous tissue, which suggests the resorption
      of the disc in the epidural space of the rabbit, whereas high-dose steroid
      suppressed the replacement.

PMID- 9580954
TI  - The effect of epidural injection of betamethasone or bupivacaine in a rat model
      of lumbar radiculopathy.
AB  - STUDY DESIGN: The effect of epidural injection of betamethasone or bupivacaine
      was investigated in an animal model of lumbar radiculopathy. OBJECTIVE: To
      investigate the effects of an epidural steroid (betamethasone) or a local
      anesthetic (bupivacaine) in an animal model of radiculopathy produced by nerve
      root irritation. SUMMARY OF BACKGROUND DATA: Epidural injections are commonly
      used for the treatment of low back pain and sciatica. However, efficacy remains
      controversial, and there is a paucity of basic information to support clinical
      use or the injections. METHODS: Fifty-one rats were used. The left L4 and L5
      nerve roots were loosely ligated with chromic gut, and either betamethasone,
      bupivacaine, betamethasone in combination with bupivacaine, or saline was
      injected using an epidurally placed catheter. The effects of epidural injection
      were evaluated using response to noxious stimuli and immunohistochemical methods.
      RESULTS: In betamethasone-treated rats (either alone or in combination with
      bupivacaine), thermal hyperalgesia was significantly less (P < 0.010 after
      surgery than that in saline- or bupivacaine-treated groups, in which the
      hyperalgesia was maximum at 2-3 postoperative weeks before resolving 5 weeks
      after surgery. Immunohistochemical analysis did not correlate with these results.
      CONCLUSIONS: Epidural steroid injection has a significant effect on the thermal
      hyperalgesia produced in a model of radiculopathy, which may provide clinical
      support for advocates of epidural steroids.

PMID- 9580955
TI  - Biomechanical evaluation of anterior cervical spine stabilization.
AB  - STUDY DESIGN: An in vitro biomechanical study. OBJECTIVES: To simulate a severe
      compressive flexion injury for determination of the relative stability of
      different anterior instrumentation systems in a porcine model and to validate
      this model in human cadaveric specimens. SUMMARY OF BACKGROUND DATA: Anterior
      plate fixation is useful for high-grade mechanical insufficiency of the cervical
      spine and may prevent the need for a second procedure. METHODS: The cervical
      spines of 45 porcine and 12 cadaveric specimens were subjected to nondestructive
      flexion, lateral bending, and torsional testing on a modified universal testing
      machine. A corpectomy was performed with release of the posterior ligamentous
      structures. The specimens were stabilized with one of three anterior plate
      constructs. The nondestructive testing was repeated to evaluate structural
      stability (stiffness and neutral zone). Finally, destructive testing examined
      failure moment, energy to failure, and mechanism of failure. RESULTS: The
      instrumented specimens had flexural and lateral bending and torsional stiffness
      values that were similar to or greater than those of their paired intact
      specimens. The cervical spine locking plate had a significantly higher flexural
      stiffness ratio (plated:intact), torsional stiffness ratio, lower flexural
      neutral zone ratio, higher failure moment, and higher energy to failure than did
      the Caspar plate. CONCLUSIONS: The cervical spine locking plate is theoretically
      safer than the Caspar system because the posterior vertebral body cortex is not
      breached by the fixation screws, and the screws are less likely to back out
      anteriorly and irritate the esophagus. According to these results, the cervical
      spine locking plate system is biomechanically equivalent to and in some cases
      more stable than the Caspar system for fixation of a severe compressive flexion
      injury.

PMID- 9580956
TI  - Quantitative anthropometry of the subatlantal cervical longitudinal ligaments.
AB  - STUDY DESIGN: The quantitative anthropometry of the cervical longitudinal
      ligaments was determined in 20 human cadaveric subatlantal cervical spines at the
      limits of flexion and extension. OBJECTIVES: To provide measurements of cervical
      anterior and posterior longitudinal ligament lengths, widths, and cross-sectional
      areas at segmental levels. SUMMARY OF BACKGROUND DATA: Although mathematical
      models of the cervical spine require specific data to predict kinematics, the
      anthropometry of the cervical spine has not been examined in detail. The
      dimensional changes of ligaments in physiologic motion are not well
      characterized. METHODS: Segmental lengths and widths of the cervical longitudinal
      ligaments were measured in sagittal plane flexion and extension, using a three
      dimensional electromagnetic digitizer. The cross-sectional areas of the ligaments
      at resting length were measured with a laser micrometer system. Comparisons
      between anterior and posterior location and among segmental levels were made.
      Several ligaments were examined histologically to determine the insertion sites
      and, thus, to define the segmental length. RESULTS: The anterior longitudinal
      ligaments were shorter in flexion than in extension. In extension, they were
      longer than the posterior longitudinal ligaments in flexion. The resting isolated
      ligaments were longer than the longest in situ lengths at several vertebral
      levels. The anterior longitudinal ligaments were wider at the disc than at the
      body. The cross-sectional area at C2-C3 was smaller than at subaxial levels. The
      longitudinal ligaments were observed to insert along the entire underlying
      vertebral body. CONCLUSIONS: The quantitative anthropometry of the cervical
      longitudinal ligaments is important in the development of accurate mathematical
      models of the cervical spine. The in situ ligaments may not be under tension in
      the physiologic range of motion.

PMID- 9580957
TI  - Effect of the pedicle and posterior arch on vertebral body strength predictions
      in finite element modeling.
AB  - STUDY DESIGN: A finite element study to predict the contribution of the pedicles
      and the posterior arch to vertebral body strength. OBJECTIVE: To determine the
      effect of the pedicle and posterior arch on strain distributions occurring within
      the vertebral body under axial compressive loading. SUMMARY OF BACKGROUND DATA:
      Posterior vertebral body fracture can arise from high-impact or normal loading in
      bones compromised by osteoporosis or neoplasm and can result in spinal canal
      encroachment. Anatomically, the pedicles and posterior arch have a potential role
      as a structural buttress to the posterior vertebral body wall. However, most
      finite element models used to investigate vertebral body strength have neglected
      these structures. METHODS: Three 3-dimensional finite element models were
      developed of L1, incorporating anatomic curvature, with varying degrees of
      posterior element inclusion (no pedicle, pedicle, and pedicle and posterior
      arch). Three cases were analyzed with each model: 25% dehydrated disc, normal
      healthy disc, and uniform pressure loading. Outcome variables were the maximum
      von Mises strains and the displacement of the posterior wall into the spinal
      canal. RESULTS: Inclusion of the posterior arch resulted in substantial decreases
      in maximum strain and posterior wall displacement under all loading
      configurations using transversely isotropic trabecular bone properties. No
      changes in maximum strains or displacements were recorded in the pedicle model,
      compared with that observed in the no-pedicle baseline case. CONCLUSIONS: The
      pedicle functions as a structural buttress, providing support to the posterior
      wall of the vertebral body when constrained through the posterior arch. To yield
      more accurate vertebral body strength predictions from finite element modeling,
      the posterior arch should be included.

PMID- 9580958
TI  - Anterior vertebral body screw pullout testing. A comparison of Zeilke, Kaneda,
      Universal Spine System, and Universal Spine System with pullout-resistant nut.
AB  - STUDY DESIGN: A biomechanical study of pullout of anteriorly implanted screws in
      cadaveric vertebral bodies. OBJECTIVES: To investigate and compare the pullout
      strength of the Zielke, Kaneda, Universal Spine System (USS) pedicle screw, and
      USS pedicle screw with a new pullout-resistant nut. SUMMARY OF BACKGROUND DATA: A
      common problem with anterior purchase regardless of the implant system is screw
      pullout at the proximal and distal ends of multilevel constructs. There is
      limited information on a solution to this problem. METHODS: The L1 to L4
      vertebral bodies from four cadavers had one each of Zielke and Kaneda pedicle
      screws (Acromed Corp., Cleveland, OH), USS pedicle screw (Synthes Spine, Paoli,
      PA), and USS pedicle screw with pullout-resistant nut implanted transversely
      across the center of the vertebral body with bicortical purchase in a similar
      fashion as would be used clinically. The screws were extracted using a
      servohydraulic material testing system. The maximum axial forces were recorded.
      RESULTS: The Zielke and Kaneda screws had no significant difference in mean
      pullout strength (P = 0.542). The USS screw alone was less strong (P = 0.009).
      The USS screw and pullout-resistant nut increased the pullout strength by twofold
      (P = 0.00006). In the screw pullout tests, the mode of failure was at the screw
      thread's interface. The USS screw and pullout-resistant nut failed by imploding
      the body around the nut. With the USS screw and pullout-resistant nut, the
      pullout strength was determined by the compressive strength of the bone.
      CONCLUSIONS: The addition of a pullout-resistant nut to an anterior vertebral
      body screw improves the pullout strength by twofold and changes the mode of
      failure to rely ultimately on the inherent vertebral body strength rather than
      the screw's characteristics. The addition of a pullout-resistant nut may be
      applicable to multilevel implant constructs to prevent screw pullout at the top
      and bottom.

PMID- 9580959
TI  - Reoperation in patients after anterior cervical plate stabilization in
      degenerative disease.
AB  - STUDY DESIGN: Consecutive case retrospective chart review. OBJECTIVES: First, to
      assess whether the number of' patients requiring a second cervical surgical
      intervention was changed as a result of using anterior cervical plate
      stabilization, and second, to determine the additional risks and/or benefits
      associated with the hardware implantation. SUMMARY OF BACKGROUND DATA: The
      optimal technique of performing stabilization, arthrodesis, and alignment of a
      cervical segment after discectomy with neural decompression in degenerative
      disease has yet to be determined. METHODS: The charts of 402 patients who had
      undergone an anterior cervical discectomy and arthrodesis for degenerative
      disease performed both with and without anterior cervical plate stabilization
      were reviewed, and reoperation data were compiled. The average follow-up time was
      3.8 years (range, 1.5-9.4 years). RESULTS: Of 365 patients with 1- or 2-level
      cervical arthrodesis, 22 required a second surgical intervention (20 bone alone,
      2 with anterior cervical plate stabilization). The Log-Rank test, which uses all
      patients and their total follow-up periods, was statistically significant
      favoring anterior cervical plate stabilization at one and two levels (P = 0.015).
      CONCLUSIONS: The addition of anterior cervical plate stabilization in one- and
      two-level cervical degenerative disease supplements the internal stabilization
      initially provided by the bone graft, and yields a lower reoperation rate.

PMID- 9580960
TI  - The correlation between surface measurement of head and neck posture and the
      anatomic position of the upper cervical vertebrae.
AB  - STUDY DESIGN: Repeated measurements were made of surface postural angles
      registering the relative positions of the head and neck in photographs and of
      angles of the upper cervical vertebrae recorded in lateral cephalometric
      radiographs in the same subjects. For all registrations, subjects assumed the
      natural head rest position. OBJECTIVES: To examine the correlation between
      external measurement of head and neck posture and the anatomic positions of the
      upper four cervical vertebrae. SUMMARY OF BACKGROUND DATA: Interpretation of
      surface cervical posture measurement is confounded by lack of knowledge about the
      extent of the underlying compensatory adjustments among the upper cervical
      vertebrae that may accompany variation in head and neck posture. The correlation
      between surface measurement and postural characteristics of the upper cervical
      spine has not been reported to date. METHODS: The association between a set of
      angles describing the anatomic position of the four upper cervical vertebrae on
      lateral cephalometric radiographs and a surface measurement of head and neck
      posture, the craniovertebral angle, was studied in 34 young adult women aged
      between 17.2 and 30.5 years, mean age, 24.5 years. Anatomic positions of the
      upper four cervical vertebrae were expressed by angles relative to the true
      vertical or horizontal. Surface angles registering head and neck position for
      each subject were obtained from photographs recorded on two occasions. RESULTS:
      No strong correlation could be established between the angles taken from the
      lateral cephalometric radiographs measuring the extent of upper cervical
      lordosis, orientation of the atlas, vertebral inclination, or odontoid process
      tilt and surface angles recording head and neck position. This finding was
      attributed principally to the much greater positional variability demonstrated
      within the upper cervical spine when compared with the surface measurements of
      head and neck position. CONCLUSION: Anatomic alignment of the upper cervical
      vertebrae cannot be inferred from variation in surface measurement of head and
      neck posture. This is the case even in those people identified with more extreme
      head and neck postural tendencies.

PMID- 9580961
TI  - Changes in cross-sectional area of psoas major muscle in unilateral sciatica
      caused by disc herniation.
AB  - STUDY DESIGN: A clinical prospective cohort study of 15 healthy volunteers and 25
      patients with unilateral sciatica from single-level disc herniation. OBJECTIVES:
      To detect any changes in the cross-sectional area of the psoas major muscle in
      patients with single-level (lateral to mediolateral) disc herniation causing
      unilateral sciatica. SUMMARY OF BACKGROUND DATA: The exact role of the psoas
      major muscle in the origin of low back pain and sciatica has not been clarified.
      METHODS: Fifteen healthy volunteers and 25 patients with unilateral sciatica from
      single-level disc herniation were subjected to magnetic resonance imaging of the
      lumbar spine. The cross-section area of the psoas major muscle on either side was
      recorded, and differences were noted. In patients, the cross-section area of
      either side was compared with and duration of sciatica was related to changes in
      the cross-section area. RESULTS: Insignificant variation in the cross-section
      area of the psoas major was observed in volunteers. In the patient group,
      significant reduction in the cross-section area of the psoas major was observed
      at the level and the site of the disc herniation. A significant correlation
      between cross-section area of the psoas major and ipsilateral continuous sciatica
      was found. There was no relation between the reduction of the cross-section area
      and the amount of disc herniation. CONCLUSION: The cross-section area of the
      psoas major is ipsilaterally decreased in unilateral lumbar disc herniation. The
      reduction in cross-section area is positively correlated with the duration of
      continuous sciatica.

PMID- 9580962
TI  - Neuromonitoring of an experimental model of clip compression on the spinal nerve
      root to characterize acute nerve root injury.
AB  - OBJECTIVES: To evaluate the sensitivity of an electro-monitoring method in acute
      nerve root injury, and to determine a proposed criterion for irreversible
      electrophysiologic degradation. STUDY DESIGN: Acute nerve root injury was induced
      by a clip compression model in rabbits, mimicking nerve root injury by a
      transpedicular screw. A common neuromonitoring technique, spinal somatosensory
      evoked potential, was used to study the electrophysiologic change during the
      procedure. SUMMARY OF BACKGROUND DATA: With the advent of the transpedicular
      screw system, increased risk of injury to the spinal root because of the passage
      of screws is not unexpected. Although both an experimental model and a clinical
      application in intraoperative neuromonitoring of spinal cord function have been
      established, the value of neuromonitoring of an acute spinal root injury remains
      obscure. Several neurophysiologic surveillance techniques have been used
      successfully to monitor the potential injury to the spinal cord during orthopedic
      procedures around the spinal cord and spinal column. Spinal somatosensory-evoked
      potential, which has the advantages of high amplitude and quick recording time,
      is used to detect nerve root impairment during the insertion of transpedicular
      screws. METHODS: Experimental acute nerve root injury was induced in rabbits by
      direct hemostatic clip compression on the nerve root (S1) during different time
      intervals. Spinal somatosensory-evoked potential elicited by stimulating the
      sciatic nerve and recorded from a needle electrode at the L6-L7 interspinous
      ligament was monitored immediately before and after compression. RESULTS: Spinal
      somatosensory-evoked potential is sensitive enough to detect the compromise of a
      single nerve root and that a decrease in the amplitude is the most reliable and
      sensitive sign. With this model, there was a statistically significant
      correlation between the compression time and reduction of amplitude and delay of
      latency. The criterion for irreversible electrophysiologic change was an
      amplitude loss of more than 20% and a delay in latency immediately after nerve
      root compression. CONCLUSIONS: It was concluded that spinal somatosensory-evoked
      potential can provide immediate feedback of nerve root injury and should be
      considered for use during the dynamic phase of transpedicular screw insertion.

PMID- 9580963
TI  - Effect of patient position and hypotensive anesthesia on inferior vena caval
      pressure.
AB  - STUDY DESIGN: This is a prospective study to measure the inferior vena caval
      pressure of 20 patients in different positions and different states of blood
      pressure. OBJECTIVES: Because the inferior vena caval pressure could affect the
      vertebral venous pressure, which in turn may influence blood loss during lumbar
      spinal surgery, this study was designed to provide the quantitative data
      necessary to stress the importance of patient positioning and to assess the
      effect of controlled hypotension on inferior vena caval pressure. SUMMARY OF
      BACKGROUND DATA: Positioning patients with a pendulous abdomen and controlled
      hypotension has been practiced widely during lumbar spinal surgery. It is
      generally believed that the former will help reduce vertebral venous engorgement
      and the latter will produce a bloodless surgical wound. However, there have been
      no complete studies in which quantitative changes of inferior vena caval pressure
      resulting from different positions was examined. In addition, it would be
      interesting to know what happens to inferior vena caval pressure during induced
      hypotension. Could there be an adverse effect on the inferior vena caval pressure
      during the hypotensive state? METHODS: An intravenous catheter was introduced
      into the inferior vena cava in each of 20 patients undergoing spinal surgery. In
      each patient, the inferior vena caval pressure was measured when the patient was
      supine, prone on a conventional pad, and prone on a Relton-Hall frame. It was
      followed by isoflurane-induced hypotension with reduction of mean arterial
      pressure by 20 mm Hg. RESULTS: In this series, the inferior vena caval pressure
      ranged from 8.2 to 23.4 mm Hg (with a mean of 15.3 mm Hg) when patients were
      positioned prone on a conventional pad. However, when they were subsequently
      positioned prone on a Relton-Hall frame, the inferior vena caval pressure
      decreased dramatically to a range of 4.6 to 13.6 mm Hg (with a mean of 8.2 mm
      Hg). In each patient the measured inferior vena caval pressure when positioned
      prone on a conventional pad was 1.5 times greater than that measured with the
      patient positioned on a Relton-Hall frame. There was a statistically significant
      difference between these two positions (F = 75.996; P < 0.05). The patients' mean
      arterial pressure ranged from 92 to 105 mm Hg before induced hypotension. During
      this time, the inferior vena caval pressure ranged from 4.1 to 13.1 mm Hg (mean,
      8.2 mm Hg). During the hypotensive state, the patients' inferior vena caval
      pressure was found to range from 4.2 to 13.6 mm Hg (mean, 8.1 mm Hg). In each
      patient the hypotensive interior vena caval pressure may be slightly higher or
      lower than the baseline pressure. However, the variation never exceeded 1.7 mm
      Hg. Statistically, there was no significant difference between these two periods
      (t = 0.956; P > 0.05). CONCLUSIONS: A device allowing the patient's abdominaL
      viscera to hang freely while the patient is in a prone position significantly
      reduces their inferior vena caval pressure. The patients also has a constant
      inferior vena caval pressure during isoflurane-induced hypotension.

PMID- 9580964
TI  - Reduction technique for uni- and biarticular dislocations of the lower cervical
      spine.
AB  - STUDY DESIGN: A technical report concerning the methods of reduction of
      dislocations of the lower cervical spine used in 168 consecutive cases (77
      unilateral and 91 bilateral dislocations). OBJECTIVES: To evaluate the efficacy
      of a reduction protocol comprising three successive phases: reduction by
      traction, reduction by closed maneuvers with the patient under general
      anesthesia, and open reduction. SUMMARY OF BACKGROUND DATA: Management of
      cervical dislocations varies greatly among spine treatment centers, especially
      concerning the upper limit of traction, the safety of closed manipulations in
      anesthetized patients, and the approach preferred when surgical reduction is
      necessary. METHODS: Reduction by gradual traction without anesthesia was
      attempted first. In case of failure, specific closed manipulations were used with
      the patient under general anesthesia just before anterior arthrodesis was
      performed. If this failed, anterior surgical reduction was attempted. Anterior
      fusion was performed in every patient, even when closed reduction was successful,
      because of the lasting instability produced by attending ligamentous lesions.
      RESULTS: Of the patients in 168 cases of dislocation, the protocol failed in 5,
      all of whom had longstanding unilateral dislocation. Of the 91 with bilateral
      dislocation, reduction was achieved by simple traction in 39 (43%), by maneuvers
      with the patient under general anesthesia in 27 (30%), and by anterior surgery in
      25 (27%). Among the patients in 77 cases of unilateral dislocation, reduction was
      achieved by traction in 18 (23%), by external maneuvers in 28 (36%), and by
      anterior surgery in 26 (34%). In 7 patients, discal herniation engendering
      neurologic signs was resected during anterior surgery. No neurologic
      deterioration during or immediately after reduction by this protocol was
      observed. CONCLUSIONS: This protocol consists of application of rapidly
      progressive traction, followed if necessary by one or two reduction maneuvers
      with the patient under general anesthesia. If both methods fail, specific
      surgical procedures using an anterior exposure seem to be reliable, in that
      anatomic reduction was obtained in 163 of 168 patients without neurologic
      deterioration.

PMID- 9580965
TI  - Lymphatic drainage after lumbar surgery.
AB  - STUDY DESIGN: A case report of lymphatic drainage after anterior retroperitoneal
      debridement and reconstruction for lumbar osteomyelitis. OBJECTIVES: To report a
      case of protracted lymphatic drainage after anterior lumbar surgery, a
      complication that has not been reported previously. SUMMARY OF BACKGROUND DATA:
      Lymphatic drainage after transthoracic surgery is a well-recognized complication.
      The possibility of lymphatic drainage after anterior lumbar surgery is less
      likely to be considered. METHODS: The cause, clinical symptoms and appearance,
      treatment, and differential diagnosis are reviewed. RESULTS: Lymphangiography is
      useful in diagnosis and should be performed early if the diagnosis is in doubt.
      Percutaneous drainage can facilitate early wound healing. CONCLUSION: Lymphatic
      drainage should be considered in the differential diagnosis of postoperative
      wound drainage, particularly after surgical debridement for osteomyelitis.

PMID- 9580966
TI  - Local and remote sustained trigger point therapy for exacerbations of chronic low
      back pain.

PMID- 9580967
TI  - The epidemiology of low back pain in the rest of the world.

PMID- 9580968
TI  - Efficacy of five cervical orthoses in restricting cervical motion: a comparison
      study.

PMID- 9580969
TI  - The value of the physical examination in diagnosis of painful sacroiliac joint
      pathologies.

PMID- 9580970
TI  - The use of baker's yeast in the generation of asymmetric centers to produce
      chiral drugs and others compounds.
AB  - This review gives a general idea about the importance of chiral carbon in
      medicine and a way to obtain chiral building blocks with baker's yeast
      (Saccharomyces cerevisiae) or synthesis of medicaments and other organic
      compounds. Reactions with these microorganisms are cheaper and easier to be
      executed than with chemicals (for example, organometallics). Examples of
      important and practical reactions catalyzed by enzymes inside Saccharomyces
      cerevisiae are given and probable mechanisms of action of these enzymes are
      shown. Although these microbes have advantages such as low cost and availability,
      there are some cares that are necessary to be taken, like NAD(P)H dosage to
      choose strains more adequate for reduction reactions.

PMID- 9580971
TI  - Dual-task results and the lateralization of spatial orientation: artifact of test
      selection?
AB  - An investigation was conducted to identify the degree to which results regarding
      the lateralization of spatial orientation among men and women are artifacts of
      test selection. A dual-task design was used to study possible lateralization
      differences, providing baseline and dual-task measures of spatial-orientation
      performance, right- and left-hand tapping, and vocalization of "cat, dog, horse."
      The Guilford-Zimmerman Test (Guilford & Zimmerman, 1953), the Eliot-Price Test
      (Eliot & Price, 1976), and the Stumpf-Fay Cube Perspectives Test (Stumpf & Fay,
      1983) were the three spatial-orientation tests used to investigate possible
      artifacts of test selection. Twenty-eight right-handed male and 39 right-handed
      female undergraduates completed random baseline and dual-task sessions. Analyses
      indicated no significant sex-related differences in spatial-orientation ability
      for all three tests. Furthermore, there was no evidence of differential
      lateralization of spatial orientation between the sexes.

PMID- 9580972
TI  - Central, local, and overall ratings of perceived exertion during cycling and
      running by women with an external or internal locus of control.
AB  - Much research has been directed toward finding the most prominent psychological
      factors affecting ratings of perceived exertion during physical exercise. The one
      most frequently mentioned, although rarely investigated empirically, is locus of
      control. Findings from non-sport-related research indicate that individuals with
      an internal locus of control (internals) are better at using the available
      information than individuals with an external locus of control (externals). That
      finding has been attributed to the inferior information-processing capacity of
      the latter group, a deficit that might also affect the processing of exertional
      cues during physical exercise. In the present study, a group of women categorized
      as internals were compared with a similar group of externals during both
      ergometer cycling and treadmill running. The results indicated significantly
      different ratings between the groups not only for overall perceived exertion but
      also for local (muscles and joints) and central (cardiopulmonary) exertion. The
      observed differences were greater during ergometer cycling than during treadmill
      running. It is possible that the more distinct cues available during cycling,
      stemming mainly from the working muscles (local factors), presented more
      information to process, a task that the internals were better at than the
      externals.

PMID- 9580973
TI  - Electrodermal responses to implied versus actual violence on television.
AB  - The electrodermal response (EDR) of children watching a violent show was
      measured. Particular attention was paid to the type of violence (actual or
      implied) that prompted an EDR. In addition, the impact of the auditory component
      (sounds associated with violence) of the show was evaluated. Implied violent
      stimuli, such as the villain's face, elicited the strongest EDR. The elements
      that elicited the weakest responses were the actual violent stimuli, such as
      stabbing. The background noise and voices of the sound track enhanced the total
      number of EDRs. The results suggest that implied violence may elicit more fear
      (as measured by EDRs) than actual violence does and that sounds alone contribute
      significantly to the emotional response to television violence. One should not,
      therefore, categorically assume that a show with mostly actual violence evokes
      less fear than one with mostly implied violence.

PMID- 9580974
TI  - Side bias in schizophrenia: hand, foot, eye, and ear.
AB  - Schizophrenics and normal controls were examined for their side (lateral) bias in
      terms of hand, foot, eye, and ear. Preference and performance measures were
      taken. The findings indicated a rightward bias for both measures in controls and
      in participants with schizophrenia. Side pattern was congruent between those with
      and without schizophrenia, with limb lateralization (hand, foot) orthogonal to
      sense-organ lateralization (eye, ear). Analysis of right- and left-side responses
      indicated a significant group difference for eye bias and ear bias as a function
      of response measures, preference, and performance.

PMID- 9580975
TI  - Rating and recognition of peers' personal odors by 9-year-old children: an
      exploratory study.
AB  - Eighteen elementary school children assessed the pleasantness and perfumed aspect
      of familiar peers' odors, sampled through tee shirts worn without modification of
      hygienic habits. The participants were also requested to categorize the odors by
      sex and to recognize those of several target classmates varying in sex and
      socioemotional status (the participant's most preferred classmate vs. a mere
      acquaintance). The ratings of odors by familiar peers appeared consistent with
      those obtained from nonfamiliar peers and adults and varied according to the sex
      of wearer of the tee shirts. For the five categories of peers examined, as well
      as for the participants themselves, olfactory recognition was better than chance.
      Moreover, it was higher for the same-sex preferred peers than for the others only
      for the female perceivers. The results are discussed in terms of their behavioral
      relevance for peer relationships, focusing especially on (a) the relations
      between sex differences in odors and gender development and (b) the function of
      olfactory memory in the emotional regulation of friendships.

PMID- 9580976
TI  - Effects of gender constancy and figure's height and sex on young children's
      gender-typed attributions.
AB  - Young children's attributions of gender-typed activities to figures/models
      differing in height and/or sex were examined over three experiments. The
      influence of gender constancy understanding on children's gender-typed
      attributions was also examined. In Experiment 1, young children attributed
      significantly more masculine activities to male than female figures and
      significantly more feminine activities to female than male figures. Experiment 2
      confirmed the results demonstrated in Experiment 1. In Experiment 2, additional
      line-drawn stimuli and figure comparisons were incorporated; participants
      attributed significantly more masculine activities to taller than shorter male
      figures and taller than shorter female figures. In addition, children attributed
      significantly more feminine activities to taller than shorter female figures. In
      Experiment 3, participants viewed pictures of taller and shorter male and female
      models. Results confirmed those of Experiment 1, as well as most of those of
      Experiment 2. No consistent patterns of children's gender-typed attributions as a
      function of gender constancy understanding emerged in the three experiments.
      Results are discussed as they apply to unexplored tenets from Kohlberg's
      cognitive-developmental model, as well as those of gender schema models, of early
      gender role development.

PMID- 9580977
TI  - Psychology and "the Babe".
AB  - Psychologists and baseball players were among those Americans who formed
      professional associations in the last quarter of the nineteenth century.
      Psychologists used laboratory tasks to quantify mental and behavioral processes
      while sportswriters and baseball organizers measured individual and team
      performance. The most popular baseball player of the 1920s, George Herman "Babe"
      Ruth, possessed superior batting skills that were evident in the statistical
      indices of baseball performance. In 1921, he was brought to the psychological
      laboratory at Columbia University to perform standard laboratory tasks in an
      effort to discover the basis for his success in hitting home runs and to suggest
      the potential of tests for identifying future baseball stars. Baseball's
      addiction to quantitative indices of performance was thus brought together with a
      new science devoted to quantitative assessment and a desire to make such
      assessments useful. The attempt to analyze the basis of Ruth's batting skills is
      part of the history of applied psychology, sport psychology, and popular interest
      in the science of psychology.

PMID- 9580980
TI  - Evolution of nicotinic acetylcholine receptor subunits.
AB  - A phylogenetic tree of a gene family of nicotinic acetylcholine receptor subunits
      was constructed using 84 nucleotide sequences of receptor subunits from 18
      different species in order to elucidate the evolutionary origin of receptor
      subunits. The tree constructed showed that the common ancestor of all subunits
      may have appeared first in the nervous system. Moreover, we suggest that the
      alpha 1 subunits in the muscle system originated from the common ancestor of
      alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, and beta 3 in the nervous system,
      whereas the beta 1, gamma, delta, and epsilon subunits in the muscle system
      shared a common ancestor with the beta 2 and beta 4 subunits in the nervous
      system. Using the ratio (f) of the number of nonsynonymous substitutions to that
      of synonymous substitutions, we predicted the functional importance of subunits.
      We found that the alpha 1 and alpha 7 subunits had the lowest f values in the
      muscle and nervous systems, respectively, indicating that very strong functional
      constraints work on these subunits. This is consistent with the fact that the
      alpha 1 subunit has sites binding to the ligand, and the alpha 7-containing
      receptor regulates the release of the transmitter. Moreover, the window analysis
      of the f values showed that strong functional constraints work on the so-called
      M2 region in all five types of muscle subunits. Thus, the window analysis of the
      f values is useful for evaluating the degree of functional constraints in not
      only the entire gene region, but also the within-gene subregion.

PMID- 9580978
TI  - Complete mitochondrial DNA sequence of the fat dormouse, Glis glis: further
      evidence of rodent paraphyly.
AB  - The complete mitochondrial genome of the fat dormouse, Glis glis, has been
      sequenced (16,602 bp). A total of 23 complete mitochondrial mammalian genomes
      have been taken into account for phylogenetic reconstruction. Phylogenetic
      analyses were performed with parsimony, distance (stationary Markov model), and
      maximum-likelihood methods. In all cases, data strongly support the paraphyly of
      rodents, with dormouse and guinea pig in a different clade from rat and mouse,
      reaching bootstrap values of 95%. Rodent monophyly and the existence of Glires
      (Rodentia and Lagomorpha) are weakly supported, with maximum bootstrap values of
      11% and 8.6%, respectively. This result agrees with the analyses of isochore
      patterns in the nuclear genome and the B2 and B2-like retroposons, which show a
      close relationship between dormice and guinea pigs rather than between dormice
      and rats and mice.

PMID- 9580981
TI  - The kappa-carrageenase of the marine bacterium Cytophaga drobachiensis.
      Structural and phylogenetic relationships within family-16 glycoside hydrolases.
AB  - We report here cloning from the marine gliding bacterium Cytophaga drobachiensis
      of kappa-carrageenase, a glycoside hydrolase involved in the degradation of kappa
      carrageenan. Structural features in the nucleotide sequence are pointed out,
      including the presence of an octameric omega sequence similar to the ribosome
      binding sites of various eukaryotes and prokaryotes. The cgkA gene codes for a
      protein of 545 aa, with a signal peptide of 35 aa and a 229-aa-long
      posttranslationaly processed C-terminal domain. The enzyme displays the overall
      folding and catalytic domain characteristics of family 16 of glycoside
      hydrolases, which comprises other beta-1,4-alpha-1,3-D/L-galactan hydrolases,
      beta-1,3-D-glucan hydrolases (laminarinases), beta-1,4-1,3-D-glucan hydrolases
      (lichenases), and beta-1,4-D-xyloglucan endotransglycosylases. In order to
      address the origin and evolution of CgkA, a comprehensive phylogenetic tree of
      family 16 was built using parsimony analysis. Family-16 glycoside hydrolases
      cluster according to their substrate specificity, regardless of their
      phylogenetic distribution over eubacteria and eukaryotes. Such a topology
      suggests that the general homology between laminarinases, agarases, kappa
      carrageenases, lichenases, and xyloglucan endotransglycosylases has arisen
      through gene duplication, likely from an ancestral protein with laminarinase
      activity.

PMID- 9580982
TI  - Measures of divergence between populations and the effect of forces that reduce
      variability.
AB  - Wright's FST and related statistics are often used to measure the extent of
      divergence among populations of the same species relative to the net genetic
      diversity within the species. This paper compares several definitions of FST
      which are relevant to DNA sequence data, and shows that these must be used with
      care when estimating migration parameters. It is also pointed out that FST is
      strongly influenced by the level of within-population diversity. In situations
      where factors such as selection on closely linked sites are expected to have
      stronger effects on within-population diversity at some loci than at others,
      differences among loci can result entirely from differences in within-population
      diversities. It is shown that several published cases of differences in FST among
      regions of high and low recombination in Drosophila may be caused in this way.
      For the purpose of comparisons of levels of between-population differences among
      loci or species which are subject to different intensities of forces that reduce
      variability within local populations, absolute measures of divergence between
      populations should be used in preference to relative measures such as FST.

PMID- 9580984
TI  - The evolution of the alcohol dehydrogenase gene family by loss of introns in
      plants of the genus Leavenworthia (Brassicaceae).
AB  - We present results showing that several species in the plant genus Leavenworthia,
      in the Brassica family, have three alcohol dehydrogenase loci, unlike Arabidopsis
      thaliana, which has only a single classical (class P) alcohol dehydrogenase
      locus. Based on a portion of the sequence, the alcohol dehydrogenase loci of
      Leavenworthia show about 92%-93% amino acid sequence identity to that of the A.
      thaliana alcohol dehydrogenase. The great majority of the sequence differences
      from the A. thaliana Adh-coding sequence, and also between three different
      Leavenworthia species, are synonymous, suggesting that all are currently
      functional (or have been in the recent evolutionary past). The loci differ in the
      numbers of introns present, with one locus (Adh-3) having no introns present. RT
      PCR tests detect expression of all three loci. Linkage data using variant alleles
      identified by single-strand conformation polymorphism analysis show that the
      three Leavenworthia loci are not closely linked. The results therefore suggest
      that the Adh-3 locus may have arisen via an mRNA intermediate but, despite loss
      of the introns, is expressed.

PMID- 9580985
TI  - The "five-sites" rule and the evolution of red and green color vision in mammals.
AB  - Amino acid changes S180A (S-->A at site 180), H197Y, Y277F, T285A, and A308S are
      known to shift the maximum wavelength of absorption (lambda max) of red and green
      visual pigments toward blue, essentially in an additive fashion. To test the
      generality of this "five-sites" rule, we have determined the partial amino acid
      sequences of red and green pigments from five mammalian orders (Artiodactyla,
      Carnivora, Lagomorpha, Perissodactyla, and Rodentia). The result suggests that
      cat (Felis catus), dog (Canis familiaris), and goat (Capra hircus) pigments all
      with AHYTA at the five critical sites have lambda max values of approximately 530
      nm, whereas rat (Rattus norvegicus) pigment with AYYTS has a lambda max value of
      approximately 510 nm, which is accurately predicted by the five-sites rule.
      However, the observed lambda max values of the orthologous pigments of European
      rabbit (Oryctolagus cuniculus), white-tailed deer (Odocoileus virginianus), gray
      squirrel (Sciurus carolinensis), and guinea pig (Cavia procellus) are
      consistently more than 10 nm higher than the predicted values, suggesting the
      existence of additional molecular mechanisms for red and green color vision. The
      inferred amino acid sequences of ancestral organisms suggest that the extant
      mammalian red and green pigments appear to have evolved from a single ancestral
      green-red hybrid pigment by directed amino acid substitutions.

PMID- 9580986
TI  - Likelihood ratio tests for detecting positive selection and application to
      primate lysozyme evolution.
AB  - An excess of nonsynonymous substitutions over synonymous ones is an important
      indicator of positive selection at the molecular level. A lineage that underwent
      Darwinian selection may have a nonsynonymous/synonymous rate ratio (dN/dS) that
      is different from those of other lineages or greater than one. In this paper,
      several codon-based likelihood models that allow for variable dN/dS ratios among
      lineages were developed. They were then used to construct likelihood ratio tests
      to examine whether the dN/dS ratio is variable among evolutionary lineages,
      whether the ratio for a few lineages of interest is different from the background
      ratio for other lineages in the phylogeny, and whether the dN/dS ratio for the
      lineages of interest is greater than one. The tests were applied to the lysozyme
      genes of 24 primate species. The dN/dS ratios were found to differ significantly
      among lineages, indicating that the evolution of primate lysozymes is episodic,
      which is incompatible with the neutral theory. Maximum-likelihood estimates of
      parameters suggested that about nine nonsynonymous and zero synonymous nucleotide
      substitutions occurred in the lineage leading to hominoids, and the dN/dS ratio
      for that lineage is significantly greater than one. The corresponding estimates
      for the lineage ancestral to colobine monkeys were nine and one, and the dN/dS
      ratio for the lineage is not significantly greater than one, although it is
      significantly higher than the background ratio. The likelihood analysis thus
      confirmed most, but not all, conclusions Messier and Stewart reached using
      reconstructed ancestral sequences to estimate synonymous and nonsynonymous rates
      for different lineages.

PMID- 9580987
TI  - Evolutionary rates for tuf genes in endosymbionts of aphids.
AB  - The gene encoding elongation factor Tu (tuf) in aphid endosymbionts (genus
      Buchnera) evolves at rates of 1.3 x 10(-10) to 2.5 x 10(-10) nonsynonymous
      substitutions and 3.9 x 10(-9) to 8.0 x 10(-9) synonymous substitutions per
      position per year. These rates, which are at present among the most reliable
      substitution rates for protein-coding genes of bacteria, have been obtained by
      calibrating the nodes in the phylogenetic tree produced from the Buchnera EF-Tu
      sequences using divergence times for the corresponding ancestral aphid hosts. We
      also present data suggesting that the rates of nonsynonymous substitutions are
      significantly higher in the endosymbiont lineages than in the closely related
      free-living bacteria Escherichia coli and Salmonella typhimurium. Synonymous
      substitution rates for Buchnera approximate estimated mutation rates for E. coli
      and S. typhimurium, as expected if synonymous changes act as neutral mutations in
      Buchnera. We relate the observed differences in substitution frequencies to the
      absence of selective codon preferences in Buchnera and to the influence of
      Muller's ratchet on small asexual populations.

PMID- 9580988
TI  - The frequency distribution of gene family sizes in complete genomes.
AB  - We compare the frequency distribution of gene family sizes in the complete
      genomes of six bacteria (Escherichia coli, Haemophilus influenzae, Helicobacter
      pylori, Mycoplasma genitalium, Mycoplasma pneumoniae, and Synechocystis sp.
      PCC6803), two Archaea (Methanococcus jannaschii and Methanobacterium
      thermoautotrophicum), one eukaryote (Saccharomyces cerevisiae), the vaccinia
      virus, and the bacteriophage T4. The sizes of the gene families versus their
      frequencies show power-law distributions that tend to become flatter (have a
      larger exponent) as the number of genes in the genome increases. Power-law
      distributions generally occur as the limit distribution of a multiplicative
      stochastic process with a boundary constraint. We discuss various models that can
      account for a multiplicative process determining the sizes of gene families in
      the genome. In particular, we argue that, in order to explain the observed
      distributions, gene families have to behave in a coherent fashion within the
      genome; i.e., the probabilities of duplications of genes within a gene family are
      not independent of each other. Likewise, the probabilities of deletions of genes
      within a gene family are not independent of each other.

PMID- 9580989
TI  - Detecting recombination from gene trees.
AB  - In this article, a method is proposed for detecting recombination in the
      sequences of a gene from a set of closely related organisms. The method, the
      Homoplasy Test, is appropriate when the sequences are rather similar, differing
      by 1%-5% of nucleotides. It is effective in detecting relatively frequent
      recombination between a set of rather similar strains, in contrast to previous
      methods which detect rare or unique transfers between more distant strains. It is
      based on the fact that, if there is no recombination and if no repeated mutations
      have occurred (homoplasy), then the number of polymorphic sites, v, is equal to
      the number of steps, t, in a most-parsimonious tree. If the number of "apparent
      homoplasies" in the most-parsimonious tree, h = t-v, is greater than zero, then
      either homoplasies have occurred by mutation or there has been recombination. An
      estimate of the distribution of h expected on the null hypothesis of no
      recombination depends on Se, the "effective site number," defined as follows: if
      ps is the probability that two independent substitutions in the gene occur at the
      same site, then Se = 1/ps. Se can be estimated if a suitable outgroup is
      available. The Homoplasy Test is applied to three bacterial genes and to
      simulated gene trees with varying amounts of recombination. Methods of estimating
      the rate, as opposed to the occurrence, of recombination are discussed.

PMID- 9580990
TI  - Gene and domain duplication in the chordate Otx gene family: insights from
      amphioxus Otx.
AB  - We report the genomic organization and deduced protein sequence of a
      cephalochordate member of the Otx homeobox gene family (AmphiOtx) and show its
      probable single-copy state in the genome. We also present molecular phylogenetic
      analysis indicating that there was single ancestral Otx gene in the first
      chordates which was duplicated in the vertebrate lineage after it had split from
      the lineage leading to the cephalochordates. Duplication of a C-terminal protein
      domain has occurred specifically in the vertebrate lineage, strengthening the
      case for a single Otx gene in an ancestral chordate whose gene structure has been
      retained in an extant cephalochordate. Comparative analysis of protein sequences
      and published gene expression patterns suggest that the ancestral chordate Otx
      gene had roles in patterning the anterior mesendoderm and central nervous system.
      These roles were elaborated following Otx gene duplication in vertebrates,
      accompanied by regulatory and structural divergence, particularly of Otx1
      descendant genes.

PMID- 9580991
TI  - Estimating times of divergence with a change of rate: the orangutan/African ape
      divergence.

PMID- 9580992
TI  - L1 repeat is a basic unit of heterochromatin satellites in cetaceans.

PMID- 9580994
TI  - 26th Annual International Neuropsychological Society Conference. Honolulu,
      Hawaii, USA. February 4-7, 1998. Abstracts.

PMID- 9580995
TI  - Keio University International Symposia for Life Sciences and Medicine.
      Neuroscience: Frontiers of Neural Development. Tokyo, Japan, December 1-4, 1997.

PMID- 9580993
TI  - A threshold size for microsatellite expansion.

PMID- 9580996
TI  - Addiction journals: amazing happenings, landmark meeting, historic consensus,
      evolving process.

PMID- 9580997
TI  - The Farmington Consensus.

PMID- 9580998
TI  - E. M. Jellinek and the evolution of alcohol studies: a critical essay.
AB  - The career of E. M. Jellinek and his impact on the evolution of the modern
      alcohol studies field is examined. Special attention is paid to his statistical
      and theoretical contributions, his work with the Yale Section of Alcohol Studies
      and the World Health Organization, and his own evolving perspective toward
      alcohol problems.

PMID- 9580999
TI  - Where to publish? Some considerations among English-language addiction journals.
AB  - A search and survey of specialty periodicals in the addiction field identified 35
      English-language scientific journals that publish unsolicited research
      manuscripts. Among these, the typical addiction journal publishes a variety of
      types of articles in one of many different citation and referencing formats,
      releases four issues per year to about 1000 subscribers, annually receives more
      than 100 manuscripts for scientific review, and accepts 53 of them to be
      published without payment of an author fee. Together these 35 addiction journals
      publish over 1700 new articles each year. Addiction journals vary widely in
      acceptance rates, ranging from 26% to 95%, and averaging 53%. For better or
      worse, these journals offer ample opportunity for the reporting of scientific
      data in the addiction field.

PMID- 9581000
TI  - A natural classification of alcoholics by means of statistical grouping methods.
AB  - AIMS: The results of previous studies using statistical grouping methods for
      subtyping of alcoholics did not converge to a coherent natural classification,
      probably among other things as a consequence of improper selection of methods. As
      an alternative an analytic strategy is formulated and tested. First, a cluster
      procedure tests a categorical model of the data. If no compact isolated groups
      are detected non-metric multi-dimensional scaling is used to unravel the complex
      relations in the data by reconstructing a low dimensional spatial solution.
      DESIGN: Cross-sectional study. SETTING: In and outpatient treatment programs of
      the Amsterdam health region in The Netherlands. PARTICIPANTS: A consecutive
      sample of 277 men and women voluntarily seeking treatment for their alcohol
      problems. No exclusion criteria were applied. MEASUREMENTS: A sample of 102
      symptoms reflecting various aspects of alcoholism measured by structured self
      report questionnaire (93 symptoms) or derived from a semi-structured interview
      taken by treatment staff (nine symptoms). FINDINGS: The cluster procedure failed
      to show a fitting categorical model. Non-metric multi-dimensional scaling
      produced a three-dimensional spatial solution. The first dimension reflects the
      alcohol dependence syndrome. The second bipolar dimension reveals a male
      dominated anti-social alcoholism, and a female-dominated pattern of isolated home
      drinking. The third bipolar dimension represents chronic alcoholism, and young
      quarrelsome people from troubled families. CONCLUSIONS: The three-dimensional
      solution obtained has a high face validity and incorporates a number of aspects
      of previous classifications. The results illustrate the strength of the analytic
      strategy in unravelling complex symptomatology. Limitations of the classification
      obtained are stressed and directions for subsequent validation research are
      given.

PMID- 9581001
TI  - Project MATCH secondary a priori hypotheses. Project MATCH Research Group.
AB  - AIMS: (1) To assess the benefits of matching alcohol dependent clients to three
      treatments, based upon a priori hypotheses involving 11 client attributes; (2) to
      discuss the implications of these findings and of matching hypotheses previously
      reported from Project MATCH. SETTING AND PARTICIPANTS: (1) Clients receiving
      outpatient therapy (N = 952; 72% male); (2) clients receiving aftercare therapy
      following inpatient or day hospital treatment (N = 774; 80% male). INTERVENTION:
      Clients were randomly assigned to one of three 12-week, manual-guided, individual
      treatments: Cognitive Behavioral Coping Skills Therapy (CBT), Motivational
      Enhancement Therapy (MET) or Twelve-Step Facilitation Therapy (TSF). DESIGN: Two
      parallel but independent randomized clinical trials were conducted, one with
      outpatients, one with aftercare clients. Participants were monitored over 15
      months including a 1-year post-treatment period. Individual differences in
      response to treatment were modeled as a latent growth process and evaluated for
      17 contrasts specified a priori. Outcome measures were percentage of days
      abstinent and drinks per drinking day. FINDINGS: Two a priori contrasts
      demonstrated significant post-treatment attribute by treatment interactions: (1)
      outpatients high in anger and treated in MET had better post-treatment drinking
      than in CBT; (2) aftercare clients high in alcohol dependence had better post
      treatment outcomes in TSF; low dependence clients did better in CBT. Other
      matching effects varied over time, while still other interactions were opposite
      that predicted. CONCLUSIONS: (1) Anger and dependence should be considered when
      assigning clients to these three treatments; (2) considered together with the
      results of the primary hypotheses, matching effects contrasting these
      psychotherapies are not robust. Possible explanations include: (a) among the
      client variables and treatments tested, matching may not be an important factor
      in determining client outcomes; (b) design issues limited the robustness of
      effects; and (c) a more fully specified theory of matching is necessary to
      account for the complexity of the results.

PMID- 9581002
TI  - Outcome studies of brief alcohol intervention in general practice: the problem of
      lost subjects.
AB  - AIMS: To identify the attrition rate of eligible subjects from the general
      practice brief intervention studies, reasons for attrition, and the potential
      bias arising from lost subjects. DESIGN: Review of all published trials of brief
      intervention for excessive drinkers in primary care settings. FINDINGS: The
      attrition rate of eligible subjects from the general practice brief intervention
      studies ranges from 44.3 to 83.2% (mean 70.6%). The potential bias introduced by
      the characteristics of subjects available and not available for research is not
      adequately addressed. Where there is evidence, subjects unavailable for study or
      those lost to follow-up usually show different characteristics (e.g. younger,
      heavier drinkers, less educated) from those completing the study. CONCLUSIONS:
      Study populations in general practice-based brief alcohol interventions may have
      been those most susceptible to intervention. This suggests caution is appropriate
      in generalizing from brief intervention study results to routine primary care.

PMID- 9581003
TI  - An evaluation of two primary care interventions for alcohol abuse among Mexican
      American patients.
AB  - AIMS: This study examined the effects of two primary care interventions (a
      physician intervention and a clinic-based psychoeducational group) on drinking
      patterns, psychosocial problems and blood test results (MCV, GGT, SGOT and SGPT).
      DESIGN: Subjects were randomized into one of four treatment groups: physician
      intervention, psychoeducation, both interventions, or no intervention. Follow-up
      data were collected at 12 and 18 months. SETTING: Subjects were recruited from a
      family practice outpatient clinic managed by a public hospital. PARTICIPANTS:
      Included 175 Mexican-American female and male primary care patients who screened
      positive for alcohol abuse or dependence. These patients were not seeking help
      for alcohol problems. INTERVENTIONS: Included a brief physician intervention and
      a 6-week patient psychoeducational group. MEASUREMENTS: The Diagnostic Interview
      Schedule assessed subjects for alcohol abuse; the Addiction Severity Index
      measured alcohol-related problems, including psychosocial issues. FINDINGS: All
      four treatment groups demonstrated significant improvement over time, with few
      differences between intervention and control groups. CONCLUSIONS: Assessment can
      be confounded with brief interventions; future investigators should use non
      assessed control groups.

PMID- 9581005
TI  - A comparison of 'visible' and 'invisible' users of amphetamine, cocaine and
      heroin: two distinct populations?
AB  - AIM: To compare the characteristics of heroin, cocaine and amphetamine users
      having no history of contact with services with those of a group in contact.
      METHOD: Multiple agency sampling and field work which included 'snowballing'
      using 'privileged access interviewers'. Each subject underwent a structured
      interview which included the Severity of Dependency Scale (SDS), and completed a
      confidential, self-report questionnaire. SETTING: Three contrasting provincial
      urban locations. PARTICIPANTS: Five hundred and eighty-one regular users of the
      target drugs. Of these, 380 (65%) denied any contact with police or helping
      agencies in connection with drug use. FINDINGS: Most zero-contact users (79%)
      expressed little or no concern about their drug use, and no wish for help or
      advice. They were much more likely to use stimulants only; less likely ever to
      inject any drug or, for those that did, to share equipment; less likely to use
      opioids, amphetamine or cocaine powder on a daily basis; more likely to use
      Ecstasy; and yielded significantly lower SDS scores for all target drugs save
      crack. Prevalence of crack use was lower, but the proportion of daily users was
      the same as in the contact group. Most (69%) contact users remained concerned
      about their drug use, but 58% expressed little or no confidence that local
      services could meet their needs. In both groups, SDS scores for cocaine powder
      were comparable to those for cannabis, LSD and Ecstasy. Of the 495 cannabis
      smokers identified (85% of the sample), 72% reported daily consumption.
      CONCLUSIONS: The findings are consistent with the hypothesis that 'visible' and
      'invisible' drug users are distinct populations in terms of behavioral
      characteristics, vulnerability to compulsive use, and prevalence of drug-related
      problems or concern. Purchasers and providers with limited resources should
      concentrate on improving the range and quality of services for users already in
      contact rather than attempting to uncover invisible populations. On the basis of
      SDS scores, cocaine HCI seems to have a relatively modest addictive potential.

PMID- 9581004
TI  - Brief coping skills treatment for cocaine abuse: substance use outcomes at three
      months.
AB  - AIMS: Coping skills training, a promising treatment approach for alcoholics, was
      adapted for use with cocaine abusers and effects on outcome were investigated.
      DESIGN: A cocaine-specific coping skills training (CST) package was compared to
      an attention placebo control when both were added to a comprehensive treatment
      program. SETTING: The sites were two private substance abuse treatment
      facilities, one residential and rural, and one an urban partial hospital.
      PARTICIPANTS: Substance abusers in treatment with cocaine abuse or dependence
      were selected. INTERVENTION: The CST intervention was conducted in individual
      sessions. It involved functional analysis of high risk situations and coping
      skills training based on the functional analysis. FINDINGS: Clients who received
      CST had significantly fewer cocaine use days and the length of their longest
      binge was significantly shorter during the 3-month follow-up period compared to
      clients in the control condition. CST did not affect relapse rates or use of
      other substances. CONCLUSIONS: Results support the notion that cocaine-specific
      CST is a promising adjunct to treatment for cocaine abusers.

PMID- 9581006
TI  - HIV prevention and drug treatment services for drug misusers: a national study of
      community pharmacists' attitudes and their involvement in service specific
      training.
AB  - AIMS: To investigate the attitudes of community pharmacists towards HIV
      prevention services for drug misusers and the relationship between these and
      their involvement in service provision. DESIGN: Postal survey of a one in four
      random sample of community pharmacies (N = 2654) in England and Wales, stratified
      by Family Health Service Authority, in 1995, using up to four mailshots. SETTING:
      Community pharmacies in England and Wales. PARTICIPANTS: The community pharmacist
      in charge of the dispensary at the random sample of community pharmacies.
      MEASUREMENTS: Information on attitudes and behaviour were collected through self
      completion and postal return of structured questionnaires using questions with
      both category responses and Likert scales. FINDINGS: A 74.8% response rate was
      achieved. Community pharmacists were positive about their role in HIV prevention
      and the provision of clean injecting equipment to injecting drug users--positive
      attitudes that were more evident among those pharmacists already providing these
      services. However, they had concerns over the effect drug misusers may have on
      business and indicated a need for more training and for more role support. Only a
      minority had taken part in training on drug misuse and HIV prevention (34.7% and
      21.3%, respectively). Many community pharmacists supported the proposal that
      there should be extensions of their involvement, to include services such as
      supervising the consumption of methadone in the pharmacy (38.6%) and collecting
      used prescribed ampoules from patients (33.8%). Positive relationships were
      identified between training and attitude, and between attitude and service
      provision. Changes in attitude responses between this 1995 survey and the earlier
      1988 survey are also presented. CONCLUSIONS: Recommendations are made for further
      training and greater communication between prescriber/carer and the community
      pharmacists, for involvement of community pharmacies in new possible forms of
      service provision, and for there to be greater attention to the value of role
      support.

PMID- 9581007
TI  - The transition from injecting to smoking heroin in three Spanish cities. The
      Spanish Group for the Study of the Route of Heroin Administration.
AB  - AIMS: To measure the current prevalence of different routes of heroin
      administration among users and to describe the most frequent patterns in the
      evolution of the main route from the time of first use to the present and their
      implications for the control of the HIV epidemic. DESIGN: Cross-sectional study.
      Face-to-face interviews using a structured questionnaire. SETTING AND
      PARTICIPANTS: Nine hundred and nine regular heroin users from Madrid, Barcelona
      and Seville (about 300 per city), half of them recruited in treatment centres and
      the other half out of treatment. MEASUREMENTS: Socio-demographic characteristics,
      current and historical behaviours related to route of administration. FINDINGS:
      Before 1980 injection was the first main route of heroin administration for most
      users in Barcelona and Madrid; in Seville smoking already predominated, although
      40% of users began by injecting. Sniffing subsequently became predominant in
      Barcelona, while smoking became the predominant first route in Madrid and Seville
      (smoking has been the only first route in Seville since 1991). The prevalence of
      injection as the main route of administration during the last 30 days was 77.3%
      in Barcelona, 24.3% in Madrid and 23.9% in Seville; smoking predominated in the
      latter two cities. The factors most strongly associated with injection as the
      preferred route were city of recruitment and having a partner who injected. Some
      73% of those who stopped injecting in their last change of route stated that the
      results of their HIV test or fear of becoming infected had been important in
      making this decision. CONCLUSIONS: The change from injecting to smoking will
      greatly facilitate the control of HIV infection in Spain. However, the main
      causal factor does not appear to be the perception of HIV risk, but rather other,
      ecological factors (cultural or market-related). The absence of these factors in
      some areas may impede the spread of smoking.

PMID- 9581008
TI  - Regional variations in deaths from volatile solvent abuse in Great Britain.
AB  - AIMS: To assess geographical variations in mortality and the relationship of
      socio-economic correlates to deaths from volatile substance abuse (VSA) in Great
      Britain. DESIGN: Analysis of the National Register of deaths from VSA by linking
      the addresses (postcode) of the deceased to census enumeration districts and
      hence wards and counties. SETTING AND PARTICIPANTS: All 775 deaths in Great
      Britain listed in the national register between 1985-91. Population counts from
      the 1991 census were used as denominators. MEASUREMENT: The Poisson heterogeneity
      test was used to test the null hypothesis that all standardized mortality ratios
      were from the same population. The t-test was used to compare differences in
      Townsend Deprivation scores between wards with and without VSA deaths. Multiple
      regression was used to assess the relationship between indices of deprivation and
      deaths from VSA. FINDINGS: One-third of all VSA deaths occurred in six regions of
      Great Britain which accounted for 17% of the at risk population. There was
      considerable variation in age standardized mortality ratios (ASMR) across
      regions. A ward level analysis indicated that wards with a VSA death had
      significantly higher levels of deprivation. The Townsend deprivation index showed
      mean deprivation scores of 2.8 and 0.2, respectively, for wards with and without
      a registered death (p < 0.0001). Multiple regression at county/region level found
      that 45% of the variation in ASMR was explained by the components of the Townsend
      deprivation index. CONCLUSIONS: Factors associated with deprivation are important
      in VSA deaths and this should be taken into account in planning public health
      measures to prevent mortality.

PMID- 9581009
TI  - The influence of smoking on reward responsiveness and cognitive functions: a
      natural experiment.
AB  - AIMS: To investigate the effects of (a) nicotine abstinence and (b) cigarette
      smoking after abstinence, on reward responsiveness and cognitive functions which
      are putatively dependent on activity in the dopaminergic system implicated in
      smoking. DESIGN: During Ramadhan, Muslim smokers elected to abstain from smoking
      either for the whole month (RAMQUIT) or during daylight hours (DAYQUIT). These
      groups, and non-smokers (NOSMOKE), were assessed on two occasions 6 hours apart
      (TEST1 and TEST2). DAYQUIT participants had abstained for 6 hours at TEST1 and
      smoked a single cigarette immediately prior to TEST2. RAMQUIT participants had
      abstained for at least 10 days prior to TEST1 and remained abstinent at TEST2.
      NOSMOKE and RAMQUIT participants are a small snack prior to TEST2 to control for
      non-specific consummatory effects. SETTING: TEST1 was conducted at the mosque and
      TEST2 in participants' homes. PARTICIPANTS: All were male; mean age was 26.7
      years. Modal cigarette consumption prior to Ramadhan by both the 13 DAYQUIT and
      the 11 RAMQUIT smokers was 21-30 per day. DAYQUIT subjects rated themselves as
      more dependent. MEASUREMENTS: The Card Arranging Reward Responsivity Objective
      Test (CARROT), testing behavioural responsiveness to small financial incentive;
      digit span, measuring attention; verbal fluency, indexing frontal lobe function;
      and the two-choice guessing test (2CGT; at TEST1 only), measuring response
      stereotypy. FINDINGS: At TEST1, compared with non-smokers, both smoking groups
      showed greater stereotypy (2CG) and lower reward responsiveness (CARROT). DAYQUIT
      participants improved on all measures after smoking a single cigarette. No marked
      changes were seen in the other groups. CONCLUSION: These data suggest that (i)
      abstaining smokers have impaired dopaminergic function and (ii) nicotine
      consumption may boost their dopaminergic activity.

PMID- 9581011
TI  - Rheumatoid arthritis and metal compounds--perspectives on the role of oxygen
      radical detoxification.
AB  - Rheumatoid arthritis (RA) is characterised by migration of activated phagocytes
      and other leukocytes into synovial and periarticular tissue. Activated oxygen
      species and other mediating substances from triggered phagocytes appear to
      exacerbate and perpetuate the rheumatoid condition. Iron excesses are capable of
      aggravating the arthritic inflammation, probably through their pro-oxidant
      potentials. In contrast, therapeutically given gold salts, through a lysosomal
      loading of the metal, inhibit the triggered cells, thereby reducing the toxic
      oxygen production. Pharmacological doses of zinc also may immobilise macrophages.
      Furthermore, the copper-zinc-containing enzyme SOD (superoxide dismutase) can act
      as a scavenger of toxic oxygen in the tissues. Therapeutic remission of RA has
      been obtained following intraarticular administration of SOD. Intramuscular
      administration of copper complexes has induced remission in about 60% of RA
      patients in open studies. Another drug, penicillamine, that protects cellular
      membranes against toxic oxygen in vitro, is presumed to act as an antirheumatic
      via the SOD mimetic activity of its copper complex. Thiomalate and other thiols
      may possess similar activities. Selenium compounds also may act as oxygen radical
      scavengers. A significant alleviation of articular pain and morning stiffness was
      obtained following selenium and vitamin E supplementation in a double-blind study
      on RA patients. The observations reviewed here indicate that metal compounds and
      other antioxidants can reduce the rheumatic inflammation by reducing the cellular
      production and/or concentration of toxic oxygen species.

PMID- 9581010
TI  - Abuse of codeine-containing cough syrups: a report from India.
AB  - AIM: To study the socio-demographic and clinical profile of patients seeking
      treatment for abuse of codeine-containing cough syrups (CCS). DESIGN:
      Observational; case series. SETTING: An addiction clinic in North India.
      PARTICIPANTS: Forty-six consecutive treatment-seeking patients of DSM-III-R
      diagnosed dependence on CCS, from January 1994 to June 1995. MEASUREMENTS: Semi
      structured interview schedule for patients and their family covering socio
      demographic and clinical variables. FINDINGS: All patients were male. Many were
      young (mean age 27 years), with completed school education (85%) and from urban
      backgrounds (80%). The mean age of starting CCS use was 23 years. Initiated
      commonly through friends (89%) and often for curiosity (63%), 89% of the patients
      progressed to daily use of CCS in less than 6 months (54% in less than a month),
      and in quantities much higher than prescribed limits. Opioid-like withdrawal was
      reported by 92%. Concurrent use of other substances, psychiatric co-morbidity and
      HIV-related risk behaviour were present in 72%, 24% and 45%, respectively. Most
      of the patients reported a 'stimulant' effect of CCS ('alert', 96%; 'more
      active', 94%). CONCLUSIONS: The combination of an opioid and a sympathomimetic
      agent in the CCS may cause a special, distinct euphoretic effect. This effect,
      along with the low price, easy availability and 'pure' preparation of CCS, may be
      responsible for the rapidly rising popularity of the CCS as drugs of abuse in
      India.

PMID- 9581012
TI  - Trends in quality assurance of metal determination in clinical chemistry.
AB  - A summary is given of the main strategies that can be used to obtain high quality
      results in the determination of metals in clinical chemistry. The trends in
      quality assurance of metal analyses are discussed.

PMID- 9581014
TI  - Risk assessment in relation to neonatal metal exposure.
AB  - Rapid changes in organ development and function occur during the neonatal period.
      During this period the central nervous system is in a rapid growth rate and
      highly vulnerable to toxic effects of, e.g., lead and methylmercury. Furthermore,
      the kinetics of many metals is age-specific, with a higher gastrointestinal
      absorption, less effective renal excretion as well as a less effective blood
      brain barrier in newborns compared to adults. Due to their low body weight and
      high food consumption per kg of body weight, the tissue levels of contaminants
      can reach higher levels in newborns than in adults. Generally, there is a low
      transfer of toxic metals through milk when maternal exposure levels are low.
      However, knowledge is limited about the lactational transport of metals and the
      potential effects of metals in the mammary gland on milk secretion and
      composition. There are some data from rodents on the lactational transfer and the
      uptake in the neonate of inorganic mercury, methylmercury, lead and cadmium.
      Metal levels in human breast milk and blood samples from different exposure
      situations can give information on the correlation between blood and milk levels.
      If such a relationship exists, milk levels can be used as an indicator of both
      maternal and neonatal exposure. Better understanding of the neonatal exposure,
      including kinetics in the lactating mother and in the newborn, and effects of
      toxic metals in different age groups is needed for the risk assessment.
      Interactions with nutritional factors and the great beneficial value of breast
      feeding should also be considered.

PMID- 9581013
TI  - Chemical speciation of arsenic in serum of uraemic patients.
AB  - Chemical speciation of arsenic was carried out in serum of a total of 51 uraemic
      patients: 19 non-dialysis (ND), 18 haemodialysis (HD) and 14 continuous
      ambulatory peritoneal dialysis (CAPD) patients. The low molecular mass As species
      were separated by ion-exchange liquid chromatography and measured on-line by
      hydride generation atomic absorption spectrometry (HGAAS). The high molecular
      mass As species were separated by fast protein liquid chromatography, either size
      exclusion, ion-exchange or affinity chromatography, and the fractions were
      digested and measured off-line with HGAAS. The mean total As concentrations in
      the serum of the three groups of the uraemic patients were significantly higher
      than the reference value (6.47 +/- 4.28, 5.12 +/- 5.58 and 4.67 +/- 5.41
      micrograms l-1 for HD, ND and CAPD patients, respectively, versus the reference
      value of 0.96 +/- 1.52 micrograms l-1. The major As species in serum of the
      patients were dimethylarsinic acid (DMA) and arsenobetaine. The HD patients
      showed a significantly higher mean DMA level than ND and CAPD patients. No
      selective removal of different As species in serum of HD patients was observed
      after 4 h of haemodialysis. The inorganic As species in serum were bound to
      proteins, mainly transferrin (about 5-6% of total As in serum). This binding may
      play an important role in arsenic detoxification.

PMID- 9581015
TI  - Effect of cadmium chelating agents on organ cadmium and trace element levels in
      mice.
AB  - In experiments performed on male mice (CD-1, Charles River), the mobilizing
      effects of repeated administration of the carbodithioate analogue BLDTC [N-benzyl
      4-O-(beta-D-galactopyranosyl)-D-glucamine-N-carbodithioate+ ++] and CaDTPA
      (calcium trisodium pentetate) on cadmium deposits in the liver, kidneys, brain
      and testes were compared. The antidotes were injected alternately every 48 h over
      a period of 16 d (8 doses in total) following a previous loading with 20 doses of
      CdCl2.2.5 H2O (single doses of 3 mg kg-1 i.p.). The experiments confirmed BLDTC
      to be one of the most effective cadmium mobilizing agents. The administration of
      CaDTPA, which is known as a useful antidote in acute cadmium intoxication,
      increased the mobilizing effect of BLDTC. Cadmium elevated the concentration of
      zinc in all organs examined and the level of copper in the liver, kidneys and
      testes. This accumulation of trace elements was only partially corrected by the
      chelators. The antidotes administered alone exert only a negligible effect on the
      trace element levels in the organs.

PMID- 9581017
TI  - Concentrations of radon and decay products in various underground mines in
      western Turkey and total effective dose equivalents.
AB  - In the present work radon concentration measurements were performed for one year
      in 12 different boron, chromium and coal underground mines in Western Turkey.
      Lucas cells and nuclear track detectors were used for the measurements of radon
      and its decay products. The effects of parameters, such as type of mine, gallery
      depth and ventilation rate, on the radon concentration in mine air were examined.
      The radiation exposure doses of miners due to the inhalation of radon and radon
      daughters were determined. Gamma survey measurements were also realized together
      with radon measurements and the total effective dose equivalents in mSv y-1 were
      estimated.

PMID- 9581016
TI  - Urinary arsenic species in Devon and Cornwall residents, UK. A pilot study.
AB  - First void urine samples were collected from 24 residents in an area of past
      intense mining and smelting activity of arsenical ores. Seven samples were also
      taken from a control village. The arsenic species in the urine were separated and
      quantified with an HPLC-ICP-MS system equipped with a hydraulic high-pressure
      nebulizer. The detection limit for arsenic in urine using this system is 0.05
      microgram dm-3. Creatinine was also determined for all samples to remove the
      influence of urine density and all results were expressed in microgram As g-1
      creatinine. The results showed elevated levels of both organic and inorganic
      arsenic compounds in the 'exposed' population's urine when compared with those of
      the control group. The total As concentrations (less arsenobetaine) in the
      'exposed' population were in the range 2.7-58.9 micrograms g-1 creatinine (mean
      13.4, median 9.2 micrograms g-1) compared with the control group data range 2.5
      5.3 micrograms g-1 (mean 4.2, median 4.7 micrograms g-1).

PMID- 9581018
TI  - Selenium levels, thiobarbituric acid-reactive substance concentrations and
      glutathione peroxidase activity in the blood of women with gestosis and imminent
      premature labour.
AB  - The aim of the study was to investigate antioxidant status, monitored by selenium
      and thiobarbituric acid-reactive substance concentrations in blood plasma, and
      glutathione peroxidase activity in erythrocytes and blood plasma in women with
      gestosis (n = 26), imminent premature labour (n = 48) and normal pregnancy (n =
      23) during 19-38 weeks of pregnancy. Selenium concentrations in blood plasma were
      significantly higher in women with pathological pregnancies than in normal (45.5
      +/- 10.5 micrograms l-1, p < 0.01 and 44.1 +/- 11.6 micrograms l-1, p < 0.05 vs.
      38.6 +/- 8.3 micrograms l-1, respectively). In all groups of pregnant women Se
      concentrations were extremely low as compared with non-pregnant females.
      Glutathione peroxidase (GSH-Px) activity in blood plasma was significantly higher
      in complicated pregnancies than in healthy ones. There were no significant
      differences in thiobarbituric acid-reactive substance concentrations between all
      groups of pregnant women. Statistically significant correlations were found
      between blood plasma Se concentrations and GSH-Px activity in healthy pregnant (r
      = 0.53, p < 0.01), imminent premature labour (r = 0.39, p < 0.01), and non
      pregnant females (r = 0.56, p < 0.001).

PMID- 9581019
TI  - Iron metabolism and human ferritin heavy chain cDNA from adult brain with an
      elongated untranslated region: new findings and insights.
AB  - Ferritin is a ubiquitous protein which plays a major role in iron sequestration,
      detoxification and storage. In this paper we highlight the role of ferritin in
      iron homeostasis and describe factors and diseases that affect its expression. We
      also describe new studies which further characterize the structure and expression
      of a novel form of ferritin heavy (H) chain mRNA that was identified in brain and
      discuss possible implications of these findings. Human fetal and adult brain cDNA
      libraries previously were screened with cDNA for well-characterized liver
      ferritin H. In addition to 'liver-like' brain ferritin H cDNA, novel ferritin H
      cDNAs with an additional 279 nucleotide sequence at the 3'untranslated region
      (UTR) were identified in both libraries (see refs. 1 and 2; Dhar, M.,
      Chauthaiwale, V., and Joshi, J. G., Gene, 1993, 126, 275 and Dhar, M., and Joshi,
      J. G., J. Neurochem., 1993, 61, 2140). However, relative to liver ferritin H
      cDNA, these novel cDNAs were incomplete at their 5'ends [see ref. 3; Joshi, J.
      G., Fleming, J. T., Dhar, M. S., and Chauthaiwale, V., J. Neurol Sci., 1995, 134,
      (Suppl.), 52]. In the present paper, by sequencing of cDNAs using reverse
      transcriptase polymerase chain reaction, we show that the 279 nt 3'UTR sequence,
      a coding sequence identical to that in human liver ferritin H, and a full-length
      5'UTR that includes one mRNA regulatory iron-response element sequence, co-exist
      in at least one species of ferritin H transcript in six normal human adult and
      six late-onset, sporadic Alzheimer disease (AD) brains. This sequence is the same
      in the normal and AD brains. Dot-blot analysis of poly A+ RNAs from different
      human tissues indicates that relative to the coding sequence of ferritin H,
      expression of the 279 nt 3'UTR sequence varies among different tissues, is
      highest in the adult brain, and is very low in fetal brain. In normal adult
      hippocampus, ferritin H RNA with the novel 279 nt sequence localizes strongly to
      small non-neuronal cells, capillary endothelial cells, and to selected
      populations of neurons (granule cells of the dentate gyrus). Significant homology
      was observed between a region in the 279 nt 3'UTR segment of ferritin H RNA and
      the 3'UTR of cyclooxygenase-2 mRNA (an inducible iron-containing enzyme involved
      in prostaglandin synthesis). Possible functions for ferritin H protein derived
      from the novel message and for the elongated 3'UTR and 5'UTR are discussed.

PMID- 9581020
TI  - Testing of chelating agents and vitamins against lead toxicity using mammalian
      cell cultures.
AB  - Mammalian cell cultures were used to determine the capacity of antidotes to
      modify (a) lead uptake, (b) lead toxicity and (c) lead release from cells. The
      following chelating agents were tested: Na, Ca-ethylenediaminetetraacetic acid
      (EDTA), diethylenetriaminepentaacetic acid (DTPA), nitriloacetic acid, ethylene
      glycol-bis(aminoethyl)tetraacetic acid (EGTA), D,L-mercaptosuccinic acid (MSA),
      meso-2,3-dimercaptopropanesuccinic acid (MSA), D,L-2,3-dimercaptopropane-1
      sulfonic acid (DMPS), penicillamine (PA), N-acetylpenicillamine (NAPA), and
      diethylcarbodithioate (DDTC). The following vitamins were tested: thiamine (B1),
      riboflavine (B2), pyridoxine (B6), cobalamin (B12) and ascorbic acid (C).
      Inhibition of lead uptake was produced by EDTA, EGTA, DMSA, DMPS, MSA, PA, NAPA
      and vitamins B1, B6 and C, vitamins B2 and B12 being ineffective. The same
      compounds reduced lead cytotoxicity. Interestingly DDTC and DTPA increased lead
      uptake, but did not exacerbate lead toxicity. Significant release of lead from
      preloaded cells was caused by DTPA, NAPA, DMPS and PA, while the other chelators
      were ineffective.

PMID- 9581021
TI  - Lead concentrations and isotope ratios in street dust determined by
      electrothermal atomic absorption spectrometry and inductively coupled plasma mass
      spectrometry.
AB  - A major source of environmental lead, particularly in urban areas, has been from
      the combustion of leaded petrol. Street dust has previously been used to assess
      urban lead contamination, and the dust itself can also be a potential source of
      lead ingestion, particularly to children. The progressive reduction of lead in
      petrol, in recent years, would be expected to have been reflected in a reduction
      of lead in urban dust. We have tested this hypothesis by repeating an earlier
      survey of Manchester street dust and carrying out a comparable survey in Paris.
      Samples were collected from streets and parks, lead was extracted by digestion
      with concentrated nitric acid and determined by electrothermal atomic absorption
      spectrometry. Lead isotope ratios were measured by inductively coupled plasma
      mass spectrometry. Results for Manchester show that lead concentrations have
      fallen by about 40% (street dust averages, 941 micrograms g-1 (ppm) in 1975 down
      to 569 ppm in 1997). In Paris, the lead levels in street dust are much higher and
      significant differences were observed between types of street (not seen in
      Manchester). Additionally, lead levels in parks were much lower than in
      Manchester. Samples collected under the Eiffel Tower had very high concentrations
      and lead isotope ratios showed that this was unlikely to be fallout from motor
      vehicles but could be due to the paint used on the tower. Isotope ratios
      measurements also revealed that lead additives used in France and the UK come
      from different sources.

PMID- 9581022
TI  - Selective uptake of selenite by red blood cells.
AB  - Both organic and inorganic forms of selenium (Se) can be utilized in the body,
      and the biotransformation of selenite into an organic form of Se in the
      bloodstream is the first step for the utilization of inorganic Se. Selenite
      injected intravenously into rats was shown to be taken up rapidly and selectively
      by red blood cells (RBCs) through the anion-exchange carrier. The uptake of
      selenite by RBCs was inhibited by 4,4'-diisothiocyano-2,2'-stilbene disulfonate,
      a specific inhibitor of the anion-exchange carrier (band 3 protein). The uptake
      was also inhibited by chromate owing to the glutathione deprivation in RBCs,
      which was confirmed by the inhibition by azodicarboxylic acid bis(dimethylamide).
      The presence of hydrogencarbonate in the incubation solution slightly retarded
      the uptake of selenite by RBCs. Although Se effluxed into the plasma was bound
      selectively to albumin, plasma proteins (albumin) did not accelerate the uptake
      process. Based on these results, the rapid and selective uptake of selenite by
      RBCs was explained by the selective and efficient uptake through the anion
      exchange carrier, followed by reduction by glutathione.

PMID- 9581023
TI  - Nickel, cobalt, zinc and copper levels in brown trout (Salmo trutta) from the
      river Otra, southern Norway.
AB  - The Flat Nickel mine at Evje in southern Norway was mined extensively from 1914
      to 1945 with little regard for any potential environmental effect. Much of the
      ore extracted was smelted at a site adjacent to the river Otra south of Evje.
      Recent studies have revealed heavy metal pollution in the land surrounding the
      smelter and in water draining from the mine leading to concern for the aquatic
      ecosystem in the river Otra. Brown trout were sampled from an uncontaminated lake
      9 km upstream from the smelter, from the base of the Oddebekken (a tributary
      draining the mine water into the Otra), from sites immediately upstream and down
      stream of the smelter and from a site 4 km down stream from the smelter. Fish
      from sites adjacent to the smelter and the base of the Oddebekken were smaller
      than those from the lake and down stream site. Concentrations of the metals were
      highest in fish sampled where the mine water entered the Otra and gradually
      decreased in fish further down the river. Fish from the uncontaminated lake had
      the lowest level of metals.

PMID- 9581025
TI  - Inductively coupled plasma mass spectrometric determination of molybdenum in
      urine from a Danish population.
AB  - Molybdenum creatinine levels in urine were measured in 128 Danish inhabitants by
      ICP-MS in order to establish reference intervals of molybdenum in urine for the
      Danish population as a part of the EURO-TERVIHT project (Trace Element Reference
      Values in Human Tissues). The Mo concentration was determined using the isotopes
      95Mo and 98Mo. The values measured based on 98Mo were about 2% lower than those
      calculated using 95Mo, a negligible difference in the context of reference
      values. The limit of detection was 0.2 microgram l-1, the precision was 8.6% and
      the recovery of added NIST 1643c certified reference material was 94%. The
      distribution of the data, with and without correction for creatinine
      concentration, was long-normal. The mean concentration measured was 42.5
      micrograms l-1, (3.89 micrograms Mo mmol-1 creatinine) using 95Mo and 41.5
      micrograms l-1 (3.81 micrograms Mo mmol-1 creatinine) using 98Mo, with the 95%
      parametric reference intervals 10.0-124.0 micrograms l-1 (0.89-11.50 micrograms
      Mo mmol-1 creatinine) and 9.6-122.6 micrograms l-1 (0.84-11.47 micrograms Mo mmol
      1 creatinine), respectively. The difference between men and women reached the
      level of significance only after the values were corrected for the creatinine
      concentration. There was no influence of age on the Mo concentration. Specific
      effects of different food and beverage intakes could not be demonstrated, with
      the exception of a positive correlation between butter consumption and Mo
      concentration.

PMID- 9581024
TI  - Occupational arsenic exposure and glycosylated haemoglobin.
AB  - In a group of 40 workers occupationally exposed to arsenic (As workers)
      biological markers for cardiovascular diseases were studied. The median arsenic
      concentration in urine samples from the exposed group was 22.3 nmol of As per
      mmol of creatinine, while the individual maximum level was 294.5 nmol of As per
      mmol of creatinine. That of the reference group was 12 nmol of As per mmol of
      creatinine and significantly below the level of the exposed group (p < 0.001).
      The arsenic concentration in urine samples from colleagues of the persons working
      with arsenic containing products was similar to the arsenic concentration in
      urine samples from the As workers. The concentration of glycosylated haemoglobin
      (Hgb A1C) was increased in whole blood from the As workers. The level of the As
      workers was 5.4% (median), similar to that of colleagues (5.5%), while that of
      the reference group was 4.4%. The differences were significant (p < 0.001).
      Multiple regression analysis showed a significant connection (p = 0.034) between
      the concentration of Hgb A1C in whole blood and the arsenic level in urine from
      the As workers. The systolic blood pressure was 125 mm Hg in the As workers and
      117 mm Hg in the control group. The difference was significant (p = 0.023). It is
      concluded that arsenic exposure has an influence on carbohydrate metabolism,
      increases the systolic blood pressure and finally may result in increased risk of
      development of cardiovascular diseases.

PMID- 9581026
TI  - Strain dependence of steady-state retention and elimination of mercury in mice
      after prolonged exposure to mercury(II) chloride.
AB  - Previous studies have demonstrated that the toxicokinetics of a single oral dose
      of inorganic mercury in mice depends on the specific strain. The strain dependent
      kinetics were attributed primarily to differences in intestinal Hg2+ absorption.
      Elimination kinetics have been difficult to evaluate, however, as the majority of
      a single oral dose will pass through the gastrointestinal tract unabsorbed.
      Therefore, in contrast to previous studies, in this study exposure to inorganic
      mercury in drinking water for a prolonged time period was used in order to reach
      a steady state for whole-body retention of mercury. The exposure level (5 mg l-1)
      was sufficiently low to exclude gastrointestinal toxicity. The steady-state
      retention of mercury was established in four inbred mouse strains (B10.S, DBA,
      A.SW and SJL). The DBA strain reached the highest whole-body steady state level
      of mercury (19 micrograms Hg) whereas B10.S mice, when considering the drinking
      water consumption, had the lowest steady-state retention of mercury (15
      micrograms Hg). Analysis of the whole-body elimination of mercury after 12 weeks
      of drinking water exposure indicated that variations in the elimination kinetics
      could explain a large fraction of the observed strain differences in the steady
      state retention of mercury. Thus, the approximate half-time for elimination of
      aged mercury depots was longest in DBA mice (83 d) and shortest in B10.S mice (44
      d). Further, the observed organ depositions indicated that differences in the
      transport of mercury from the liver to kidney might also explain some of the
      differences in the elimination kinetics.

PMID- 9581027
TI  - Comparison of enhanced elimination of bismuth in humans after treatment with meso
      2,3-dimercaptosuccinic acid and D,L-2,3-dimercaptopropane-1-sulfonic acid.
AB  - Two groups of 12 human volunteers, who had been treated with colloidal bismuth
      subcitrate, because of Helicobacter pylori-associated gastritis, participated in
      the study. The patients received a single dose of meso-2,3-dimercaptosuccinic
      acid (DMSA) or D,L-2,3-dimercaptopropane-1-sulfonic acid (DMPS) at a dose of 30
      mg kg-1 in a randomized single blind study. In contrast to DMPS, increasing
      concentrations of bismuth in blood were observed during the first 4 h after
      intake of DMSA. In urine, both chelators induced a 50-fold increase in urinary
      bismuth excretion compared with the control urines. The treatment was well
      tolerated. The results indicate that both DMSA and DMPS effectively increase the
      elimination of bismuth in human urine. Consequently, both chelators may be of
      benefit in the treatment of patients with bismuth intoxication.

PMID- 9581028
TI  - Decreased selenium concentration in maternal and cord blood in preterm compared
      with term delivery.
AB  - The Se concentration in maternal and cord whole blood and plasma was determined
      spectrofluorimetrically in: (1) 42 women at term and (2) 46 at preterm
      parturients, and in the placenta. The glutathione peroxidase (GSH-Px) activity
      was measured in red cells and plasma in maternal and cord blood of both groups.
      The Se concentrations and GSH-Px activities of the above-mentioned groups were
      compared with those of non-pregnant women. Whole blood and plasma Se
      concentration of parturients at term did not differ significantly from those of
      non-pregnant women (72.3 versus 80.3 ng ml-1 whole blood and 48.7 versus 56.2 ng
      ml-1 plasma). In preterm parturients, however, Se concentrations were
      significantly lower (61.1 ng ml-1 whole blood and 39.2 ng ml-1 plasma) when
      compared with term parturients. The Se levels in cord blood and plasma were
      similar to their mothers' Se concentrations. No difference was observed in
      placenta Se levels (130 ng g-1 wet weight in both groups). The same was true for
      glutathione (GSH): the concentration in maternal and cord blood of term and
      preterm parturients did not differ and varied from 2.43 to 2.50 mmol l-1 red
      cells. Red cell GSH-Px activities were similar in maternal and cord blood of both
      term and preterm groups and ranged from 14.3 to 15.7 U g-1 Hb. The plasma enzyme
      activity in the maternal blood of preterm parturients was significantly (p <
      0.05) lower than that of mothers at term delivery. The GSH-Px activity in the
      plasma of cord blood was significantly (p < 0.001) lower in the preterm than in
      the term group. It is suggested that low Se levels in the blood of women at
      preterm delivery, as shown here, may be one of the causes of retinopathy and
      respiratory distress syndrome in preterm infants.

PMID- 9581029
TI  - Immunological effects of occupational exposure to metallic mercury in the
      population of T-cells and NK-cells.
AB  - This paper presents a study of the counts of lymphocytes, (CD3+)T-cells, (CD4+)T
      helper and (CD8+)T-suppressor and (CD16+)NK-cells in the peripheral blood of 101
      males with a history of occupational exposure to metallic mercury vapours (Hg0)
      and in 36 males without this exposure. These workers were divided depending on
      the duration of exposure: 37 males with a short-term history of exposure to Hg0
      (up to 10 years) and 64 males with a history of long-term exposure (10 to 37
      years). For the determination of T-cell populations monoclonal antibodies were
      used in indirect immunofluorescence tests. The time weighted average of mercury
      concentrations in air was 0.028 mg m-3. Mercury concentration in the urine of the
      exposed subjects ranged from 20-260 micrograms dm-3, and in blood it was from 4
      to 72 micrograms dm-3. Stimulation of the T-cell line was noted as evidenced by
      increased numbers of (CD3+)T-cells, (CD4+)T-helper and (CD8+)T-suppressor cells
      in the workers with < 10 or > 10 years' exposure to Hg0. Lower increase count of
      (CD3+)T-cells and (CD4+)T-helper cells than (CD8+)T-suppressor cells was the
      cause of decreased values in the (CD3+)T/(CD8+)T-suppressor ratio and (CD4+)T
      helper/(CD8+)T-suppressor ratio in the workers with < 10 or > 10 years' of
      exposure. Moreover, no changes were observed in the T-cell populations between
      workers with < 10 and those with > 10 years' exposure. In addition, statistical
      analysis of the effects of age and duration of exposure to Hg0 on the studied
      immunological parameters indicates that exposure duration may affect some of the
      values. These quantitative changes of T-cell population as well as changes of the
      (CD3+)T/(CD8+)T-suppressor and (CD4+)T-helper/(CD8+)T-suppressor ratio have been
      proposed as immunological indicators of exposure to Hg0, which can be used for
      monitoring and to explain the origin of autoimmunity disorders induced by
      metallic mercury.

PMID- 9581030
TI  - Determination of solvent thinner components in human body fluids by capillary gas
      chromatography with trapping at low oven temperature for headspace samples.
AB  - A simple and sensitive method is presented for determination of solvent thinner
      components in human body fluids by capillary gas chromatography (GC) with a low
      oven temperature for trapping headspace vapor components. After heating a blood
      or urine sample containing ethyl acetate, benzene, butan-1-ol, toluene, butyl
      acetate, isoamyl acetate and ethylbenzene (internal standard) in a 7.5 ml vial at
      90 degrees C for 30 min, 5 ml of headspace vapor were drawn into a glass syringe.
      All vapor was introduced through an injection port in the splitless mode into a
      DB-624 medium-bore capillary column at a 5 degrees C oven temperature for
      trapping the volatile compounds, and the oven temperature was programmed up to
      110 degrees C for their detection by GC. These conditions gave sharp peaks, a
      good separation of each peak and low background noise for both whole blood and
      urine samples. As much as 3.58-55.1 and 3.52-57.9% of the six compounds, which
      had been added to vials, could be introduced to the GC instrument for whole blood
      and urine, respectively. The intra-day RSD values in terms of the introduction
      rate (net recovery) of the six compounds in whole blood and urine samples were <
      or = 8.1%. The calibration curves showed linearity in the range 0.78-400 ng per
      0.5 ml whole blood or urine. The detection limits were 0.5-5 ng per 0.5 ml. The
      data on toluene in post mortem blood in an actual case are also presented.

PMID- 9581031
TI  - Fees and expenses.

PMID- 9581032
TI  - Amoxycillin prophylaxis for endocarditis prevention. British Society for
      Antimicrobial Chemotherapy Endocarditis Working Party.

PMID- 9581033
TI  - The ups and downs of barodontalgia.

PMID- 9581034
TI  - Mike Grace talks to Mike Joy. Interview by Mike Grace.

PMID- 9581035
TI  - Assessing and managing dental phobia in general practice: some practical
      suggestions.
AB  - An awareness of the predisposing dynamics of dental phobia allows members of the
      dental team to deal empathetically and objectively with their child and adult
      patients' anxieties and concerns. The use of communication skills and behavioural
      management techniques together with or without conscious sedation, allow the
      patient to slowly progress from experiencing phobic reactions toward dental
      treatment to a lesser form of dental anxiety.

PMID- 9581036
TI  - Rubber dam.
AB  - In a busy dental practice the many advantages of the routine use of dental dam
      for day-to-day procedures are often not appreciated. Many general dental
      practitioners (GDPs) are unaware of the simple and rapid techniques for placement
      that exist and the important role that rubber dam plays in infection control.

PMID- 9581037
TI  - Advances in periodontal diagnosis. 5. Potential inflammatory and immune markers.
AB  - The potential inflammatory and immune markers that might detect periodontal
      disease severity or activity are examined. The role of inflammatory and immune
      factors passing from the tissues into the gingival crevicular fluid (GCF) are
      considered. GCF sampling is a necessary part of all diagnostic tests based on
      gingival and periodontal tissue factors. Inflammatory and immune factors found in
      GCF are reviewed with special reference to the humoral immune response,
      complement, cytokines and prostaglandins. The possible development of diagnostic
      tests based on these factors are discussed.

PMID- 9581038
TI  - Trends in the provision of primary care dental general anaesthesia in the north
      of England, 1991/92 to 1994/95.
AB  - AIM: To investigate trends in the provision of primary care dental general
      anaesthesia (PCDGA) and any association with dental caries. DESIGN: Cross
      sectional analysis of data about the provision of PCDGA in the general dental
      service and community dental service from 1991/92 to 1994/95. SETTING: The former
      North Western, Mersey, Northern and Yorkshire regions. METHOD: The combined rates
      of PCDGAs in the general dental service and community dental service, from
      1991/92 to 1994/95 were calculated and compared with the levels of caries from
      the NHS dental epidemiology programme. RESULTS: All regions except the North
      Western had a lower rate at the end of the 1991 study but only the Northern
      region had a lower rate in 1994/95 than in 1993/94. Only weak correlations were
      found between the PCDGA rate in a health authority and the level of dental
      caries. CONCLUSIONS: PCDGA rates did not continue to decline during the period of
      this study. One of the principal recommendations of the Poswillo report was that
      the use of general anaesthesia should be avoided wherever possible. Other
      initiatives, perhaps the development of criteria for selection of patients, may
      be necessary if further reductions in PCDGA rates are to be achieved.

PMID- 9581039
TI  - An investigation of male attitudes toward marketing communications from dental
      service providers.
AB  - OBJECTIVE: To identify the process by which males aged 25-34 who do not display
      regular attendance behaviour are exposed to, attend, comprehend and are persuaded
      by communications by general dental practitioners. DESIGN: Focus groups (of 1
      hour duration) comprising 6-7 members, conducted over a period of 18 months,
      discussing five open-ended questions or statements. SETTING: The Manchester
      Metropolitan University, Crewe+Alsager Faculty, Cheshire, UK during 1995-96.
      SUBJECTS: 116 non-attending males (aged between 25-34 years) taken from
      professional lecturers (17%), full-time (50%) and part-time students (33%) with
      varying income and education levels. INTERVENTIONS: A theoretical linear
      sequential model related to patients behaviour was considered in relation to the
      timing of communications but this was not tested. MAIN OUTCOME MEASURES: Views of
      group members concerning their attitudes, perceptions and experience of
      communications from GDPs. RESULTS: Informative oral communications were
      considered as important during treatment. Most written communications were cited
      as impersonal, health posters were perceived as negative being targeted at
      children only, general media articles on dentistry were not very evident or
      interesting, however, a practice brochure was viewed as a handy communication
      tool. CONCLUSIONS: General dental practitioners should look carefully at all of
      their own methods of communication with patients (from oral to written) and
      consider the value of their marketing and all areas of communications, especially
      when considering non-attenders and males (aged 25-34).

PMID- 9581040
TI  - A new technique for the controlled removal of mottled enamel: measurement of
      enamel loss.
AB  - AIM: To describe and investigate a simple, effective new method for controlled
      removal of unsightly, malformed surface enamel. SUBJECTS AND METHODS: 22 mottled
      incisor teeth were chosen from a group of 12 patients, aged 9-15 years. One half
      of the labial surface of the tooth was covered with a layer of unfilled bis-GMA
      resin so that it remained unaffected by the procedure. The other half was treated
      by etching the enamel with 35% phosphoric acid for 30 seconds, washing and
      drying. The frosted, etched enamel was removed with a composite finishing bur
      (Jet 7901) running dry in an air turbine, until a shiny enamel surface
      reappeared. The enamel was then smoothed with a pumice and water slurry in a slow
      rotating rubber prophylaxis cup. The bis-GMA resin was peeled off, and an
      elastomeric impression of the tooth (now with one half of its labial surface
      treated, and the other untreated) was taken. The treatment of the remainder of
      the labial aspect was then completed. The thickness of the mid-labial enamel
      removed was measured directly from the impression by surface imaging, using a
      confocal microscope. RESULTS: The mean thickness of enamel removed was 164
      microns (SD +/- 85 microns). CONCLUSIONS: This technique results in equivalent
      amounts of enamel removal to that claimed for other more complex and time
      consuming methods.

PMID- 9581042
TI  - Serious hazards of transfusion (SHOT): first annual report.

PMID- 9581041
TI  - Factors affecting the lifespan of the human dentition in Britain prior to the
      seventeenth century.
AB  - OBJECTIVE: To confirm that compensatory eruption (supereruption) of teeth past a
      stable periodontium occurs in response to severe occlusal attrition. DESIGN:
      Regression analysis study from radiographs and direct measurements. SETTING:
      Archaeological material at the University of Aberdeen. SUBJECTS: 47 individuals >
      21 years old and dating from Late Mediaeval times (1300-1600 AD). MAIN OUTCOME
      MEASURES: Occlusal attrition was recorded on the first permanent mandibular
      molars. Measurements on radiographs of the teeth from the fixed point of the
      inferior dental canal were taken to the occlusal surface, the alveolar crest and
      the tooth apex. Regression analysis was undertaken between these variables and
      related to attrition (age). RESULTS: Continuous eruption of the permanent human
      dentition past a stable periodontium does occur in response to tooth height lost
      by wear, despite the fact that supereruption may lead to the eventual self
      destruction of the dentition. This mechanism was primarily responsible for the
      early loss (at 40-45 years of age) of dentitions in Mediaeval times. CONCLUSIONS:
      Stability of occlusal height appears to be an important function of the dentition
      and if triggered by severe wear will lead to increasing root exposure and
      eventual exfoliation of the teeth. It is important not to confuse bone loss due
      to periodontitis with root exposure due to supereruption of the teeth.

PMID- 9581043
TI  - Tripler's Emergency Medical Response Team.

PMID- 9581044
TI  - The role of geriatric psychiatry in medical education.

PMID- 9581045
TI  - CT demonstration of a pancreatic duct stricture and obstructive pancreatitis with
      ERCP and intraoperative correlation.
AB  - We describe a case of a pancreatic duct stricture in a young female resulting in
      chronic intermittent obstructive pancreatitis, and requiring repeated
      hospitalizations over a ten year period. The stricture was identified by computed
      tomographic (CT) scan and endoscopic retrograde cholangio-pancreatography (ERCP)
      and noted to be in the distal pancreatic duct. The patient was treated
      successfully with distal pancreatectomy. This case report illustrates the utility
      of CT scanning and ERCP in determining the etiology of pancreatitis. When a
      stricture is identified, these studies give anatomic detail that aid in intra
      operative decision making.

PMID- 9581046
TI  - Accidental poisoning in children with special reference to kerosene poisoning.
      1951.

PMID- 9581047
TI  - Who calls the Hawaii Poison Center?
AB  - The types of callers and calls received by the Hawaii Poison Center's telephone
      triage service during the last fiscal year (July 1, 1996 through June 30, 1997)
      are described. A comparison to national data for human toxic exposures is
      provided. Methods included a review of Hawaii Poison Center statistics, the
      American Association of Poison Control Centers annual report, and retrospective
      recall of cases.

PMID- 9581048
TI  - Hawaii Poison Center. Forty years of saving lives and health costs.
AB  - The Hawaii Poison Center was established because poisoning was a significant
      public health problem in the 1950s. The history and status of the Center, in the
      context of national trends and key issues in poison control public health
      infrastructure, is reviewed.

PMID- 9581049
TI  - Clinical pearls in pediatric toxicology: a systematic approach to the poisoned
      child.
AB  - Toxic ingestions in children can present various clinical dilemmas. This brief
      article will focus on some of the key clinical pearls that will enhance the
      physician's ability to approach any poisoning case in a more systematic and
      organized fashion.

PMID- 9581050
TI  - The Hawaii Poison Center: what's it worth to you?
AB  - Benefits of the Hawaii Poison Center (HPC) to the public, providers, and third
      party payers are enumerated. Financial advantages to third party payers during
      1996-7 were quantified by comparing costs for the home management of poisonings
      with alternative sources of care reported by callers, if the HPC were closed. The
      value for third party payers exceeded $2.5 million, greater than eight times the
      investment in operating the HPC, similar to national data. Since third party
      payers are the most visible beneficiary of cost savings, a case is made for their
      financial support of the HPC.

PMID- 9581051
TI  - The selected information sources on poisoning and toxicology.
AB  - The third leading cause of unintentional injury death in 1993 was poisoning by
      solids and liquids, just behind motor vehicle accidents and falls. Poisoning and
      toxicology impacts all health care professionals. Physicians and emergency
      medicine professionals manage acute care, health educators address prevention and
      public education, and researchers focus on advancements. This article is an
      introduction to selected basic through advanced print and electronic information
      sources for anyone interested in poisoning and toxicology. All sources are
      available through the Hawaii Medical Library.

PMID- 9581052
TI  - Estimation of nonlinear couplings on the basis of complexity and predictability-
      a new method applied to cardiorespiratory coordination.
AB  - Nonlinear coordination is an essential property of the complex functioning of the
      autonomic nervous system. Therefore, the coupled behavior of heart rate
      fluctuations (HRF) and respiratory movements (RM) was analyzed on the basis of
      their joint reconstruction in the phase space. Independence measures of
      complexity and predictability were approximated from the correlation integrals
      which enabled the strength of cardiorespiratory couplings to be quantified. These
      measures were validated in a simulation study of two coupled nonlinear
      oscillators in dependence on their coupling strength and respective
      synchronization effects. The cardiorespiratory coordination during quiet sleep
      and active sleep of newborn piglets was quantified by means of the proposed
      independence measures of complexity and predictability. The difference of those
      measures between the sleep states investigated was more significant than the
      difference of the respective linear coherence peaks.

PMID- 9581053
TI  - Adaptive AR modeling of nonstationary time series by means of Kalman filtering.
AB  - An adaptive on-line procedure is presented for autoregressive (AR) modeling of
      nonstationary multivariate time series by means of Kalman filtering. The
      parameters of the estimated time-varying model can be used to calculate
      instantaneous measures of linear dependence. The usefulness of the procedures in
      the analysis of physiological signals is discussed in two examples: First, in the
      analysis of respiratory movement, heart rate fluctuation, and blood pressure, and
      second, in the analysis of multichannel electroencephalogram (EEG) signals. It
      was shown for the first time that in intact animals the transition from a
      normoxic to a hypoxic state requires tremendous short-term readjustment of the
      autonomic cardiac-respiratory control. An application with experimental EEG data
      supported observations that the development of coherences among cell assemblies
      of the brain is a basic element of associative learning or conditioning.

PMID- 9581054
TI  - Estimation of conduction velocity vector fields from epicardial mapping data.
AB  - An automated method to estimate vector fields of propagation velocity from
      observed epicardial extracellular potentials is introduced. The method relies on
      fitting polynomial surfaces T(x, y) to the space-time (x, y, t) coordinates of
      activity. Both speed and direction of propagation are computed from the gradient
      of the local polynomial surface. The components of velocity, which are total
      derivatives, are expressed in terms of the partial derivatives which comprise the
      gradient of T. The method was validated on two-dimensional (2-D) simulations of
      propagation and then applied to cardiac mapping data. Conduction velocity was
      estimated at multiple epicardial locations during sinus rhythm, pacing, and
      ventricular fibrillation (VF) in pigs. Data were obtained via a 528-channel
      mapping system from 23 x 22 and 24 x 21 arrays of unipolar electrodes sutured to
      the right ventricular epicardium. Velocity estimates are displayed as vector
      fields and are used to characterize propagation qualitatively and quantitatively
      during both simple and complex rhythms.

PMID- 9581055
TI  - Dipole separability in a neuromagnetic source analysis.
AB  - By studying the ability of a one-dipole model to explain the magnetic field
      actually resulting from two dipoles, minimum requirements for a successful
      separation of two dipoles were explored. Two dipoles in different depths
      generally require a much higher signal-to-noise ratio (SNR) than two dipoles in
      the same depth. For the latter condition, the dipole distance as well as the
      angles between the moments and the line connecting the dipole locations
      (connecting line) were systematically varied. A perpendicular orientation of the
      two dipoles turned out to be the most favorable condition: the minimum distance
      required for a separation of two dipoles was more than four times smaller than
      for a configuration with both moments oriented parallel to the connecting line.
      Separability of parallel dipoles was moderately enhanced if both moments assumed
      an orientation perpendicular to the connecting line. The separability of two
      antiparallel dipoles is not limited by concurrence with a one-dipole model, but
      by the low signal amplitudes resulting from a mutual cancellation of the fields
      arising from the two dipoles, and by concurrence with a quadrupole model. The
      results are presented so that quantitative conclusions about dipole separability
      can be derived for arbitrary SNR's. The study does not generally disprove the
      common believe that magnetoencephalography has a relatively poor spatial
      resolution, but it qualifies this view by suggesting that under favorable
      conditions two sources with a distance of only 1 cm may be resolvable.

PMID- 9581056
TI  - Pharmacokinetic-pharmacodynamic model for educational simulations.
AB  - Pharmacokinetic-pharmacodynamic (PK-PD) models play an important role in
      educational simulations. The parameters of PK-PD models described in the
      scientific literature are obtained from studies in which the drug concentrations
      and the drug-effect data are measured simultaneously. Simultaneous PK-PD studies
      cannot be expected to incorporate all possible combinations of drugs and patient
      physiology that are desired for educational simulations. To solve this problem,
      we elaborate on the traditional simultaneous PK-PD model, creating a new model
      that accepts parameter data from different, more readily available,
      nonsimultaneous pharmacologic studies. These data are incorporated in the model
      using a novel estimation procedure for the parameters kc0 and EC50. A sensitivity
      analysis of the parameter estimation procedure confirms that the time of peak
      effect following a bolus and the dose-response curve are accurately reflected by
      the new model. It also demonstrates how inconsistencies among the different
      parameter sets affect simulation of the recovery phase. The model is extended to
      incorporate any monotonic parametric or nonparametric dose-response curve. For
      the neuromuscular relaxant vecuronium, we demonstrate that data from different
      pharmacologic studies are available, and that the described estimation procedure
      leads to parameter estimates that are within the standard deviations of the
      parameters determined in a simultaneous PK-PD study.

PMID- 9581057
TI  - Vaccination policies for chaos reduction in childhood epidemics.
AB  - This paper considers the problem of controlling a childhood epidemic described by
      a susceptible-infective-recovered (SIR) model. The epidemic has a chaotic
      behavior, with large outbreaks entailing considerable costs. The control problem
      is set up to perform a chaos reduction, namely to yield a beneficial compression
      of the outbreaks of infectives. A simple class of vaccination policies is
      considered with this aim.

PMID- 9581058
TI  - A flexible algorithm for construction of 3-D vessel networks for use in thermal
      modeling.
AB  - A new algorithm for the construction of artificial blood vessel networks is
      presented. The algorithm produces three-dimensional (3-D) geometrical
      representations of both arterial and venous networks. The key ingredient of the
      algorithm is a 3-D potential function defined in the tissue volume. This
      potential function controls the paths by which points are connected to existing
      vessels, thereby producing new vessel segments. The potential function has no
      physiological interpretation, but, by adjustment of parameters governing the
      potential, it is possible to produce networks that have physiologically
      meaningful geometrical properties. If desired, the veins can be generated counter
      current to the arteries. Furthermore, the potential function allows fashioning of
      the networks to the presence of bone or air cavities. The resulting networks can
      be used for thermal simulations of hyperthermia treatment.

PMID- 9581059
TI  - Radiation patterns of dual concentric conductor microstrip antennas for
      superficial hyperthermia.
AB  - The finite difference time domain (FDTD) method has been used to calculate
      electromagnetic radiation patterns from 915-MHz dual concentric conductor (DCC)
      microwave antennas that are constructed from thin and flexible printed circuit
      board (PCB) materials. Radiated field distributions are calculated in homogeneous
      lossy muscle tissue loads located under variable thickness coupling bolus layers.
      This effort extends the results of previous investigations to consider more
      realistic applicator configurations with smaller 2-cm-square apertures and
      different coupling bolus materials and thicknesses, as well as various spacings
      of multiple-element arrays. Results are given for practical applicator designs
      with microstrip feedlines etched on the backside of the PCB antenna array instead
      of previously tested bulky coaxial-cable feedline connections to each radiating
      aperture. The results demonstrate that for an optimum coupling bolus thickness of
      2.5-5 mm, the thin, flexible, and lightweight DCC antennas produce effective
      heating to the periphery of each aperture to a depth of approximately 1 cm, and
      may be combined into arrays for uniform heating of large area superficial tissue
      regions with the 50% power deposition contour conforming closely to the outer
      perimeter of the array.

PMID- 9581060
TI  - A new technique for transmission of signals from implantable transducers.
AB  - To reduce space requirements for implant electronics in in vivo telemetry
      applications, the purpose of this project was to develop and test a new data
      transmission method that utilizes the ionic properties of bodily fluids as the
      transmission medium. Motivated by an interest in using the new method to transmit
      information from a sensor which measures tension in anterior cruciate ligament
      (ACL) grafts, a sine wave was injected into a cadaver leg using platinum
      electrodes implanted into the lateral femoral epicondyle. The signal was detected
      by electromyogram (EMG) surface electrodes. The effect of transmission frequency,
      the current injected, interelectrode separation, distance of the electrodes from
      the joint line, and the surface of electrode placement on the signal attenuation
      was studied. The logarithmic relation between attenuation and frequency was
      constant from 2 kHz until 10 kHz. For frequencies above 10 kHz, the attenuation
      increased linearly at the rate of 1 dB/octave. Attenuation was inversely
      sensitive to both current and interelectrode separation with larger separations
      and currents giving less attenuation. Attenuation was significantly less for the
      lateral thigh surface than for the anterior surface and increased with increasing
      distance from the joint line for both surfaces. For the application of interest
      here, suitable values of transmission variables to avoid the possible negative
      consequences of injecting current into living tissue are a current of 3 mA
      injected at a frequency of 37 kHz. The values of reception variables for minimum
      attenuation are wide interelectrode separation (5 cm) with the electrodes placed
      5 cm proximal of the joint line on the lateral surface of the thigh. With the
      exception of the surface which is application dependent, these values of the
      reception variables should also be appropriate for other applications.

PMID- 9581061
TI  - An ultrasonic approach to localization of fiducial markers for interactive, image
      guided neurosurgery--Part I: Principles.
AB  - Fiducial markers are reference points used in the registration of image space(s)
      with physical (patient) space. As applied to interactive, image-guided surgery,
      the registration of image space with physical space allows the current location
      of a surgical tool to be indicated on a computer display of patient-specific
      preoperative images. This intrasurgical guidance information is particularly
      valuable in surgery within the brain, where visual feedback is limited. The
      accuracy of the mapping between physical and image space depends upon the
      accuracy with which the fiducial markers were located in each coordinate system.
      To effect accurate space registration for interactive, image-guided neurosurgery,
      the use of permanent fiducial markers implanted into the surface of the skull is
      proposed in this paper. These small cylindrical markers are composed of materials
      that make them visible in the image sets. The challenge lies in locating the
      subcutaneous markers in physical space. This paper presents an ultrasonic
      technique for transcutaneously detecting the location of these markers. The
      technique incorporates an algorithm based on detection of characteristic
      properties of the reflected A-mode ultrasonic waveform. The results demonstrate
      that ultrasound is an appropriate technique for accurate transcutaneous marker
      localization. The companion paper to this article describes an automatic,
      enhanced implementation of the marker-localization theory described in this
      article.

PMID- 9581063
TI  - Automatic matching of homologous histological sections.
AB  - The role of neuroanatomical atlases is undergoing a significant redefinition as
      digital atlases become available. These have the potential to serve as more than
      passive guides and to hold the role of directing segmentation and multimodal
      fusion of experimental data. Key elements needed to support these new tasks are
      registration algorithms. For images derived from histological procedures, the
      need is for techniques to map the two-dimensional (2-D) images of the sectional
      material into the reference atlas which may be a full three-dimensional (3-D)
      data set or one consisting of a series of 2-D images. A variety of 2-D-2-D
      registration methods are available to align experimental images with the atlas
      once the corresponding plane of section through the atlas has been identified.
      Methods to automate the identification of the homologous plane, however, have not
      been previously reported. In this paper we use the external section contour to
      drive the identification and registration procedure. For this purpose, we model
      the contours by B-splines because of their attractive properties the most
      important of which are: 1) smoothness and continuity; 2) local controllability
      which implies that local changes in shape are confined to the B-spline parameters
      local to that change; 3) shape invariance under affine transformation, which
      means that the affine transformed curve is still a B-spline whose control points
      are related to the object control points through the transformation. In this
      paper we present a fast algorithm for estimating the control points of the B
      spline which is robust to nonuniform sampling, noise, and local deformations.
      Curve matching is achieved by using a similarity measure that depends directly on
      the parameters of the B-spline. Performance tests are reported using histological
      material from rat brains.

PMID- 9581062
TI  - An ultrasonic approach to localization of fiducial markers for interactive, image
      guided neurosurgery--Part II: Implementation and automation.
AB  - Registration of image space and physical space lies at the heart of any
      interactive, image-guided neurosurgery system. This paper, in conjunction with
      the previous companion paper [1], describes a localization technique that enables
      bone-implanted fiducial markers to be used for the registration of these spaces.
      The nature of these subcutaneous markers allows for their long-term use for
      registration which is desirable for surgical follow-up, monitoring of therapy
      efficacy, and performing fractionated stereotactic radiosurgery. The major
      challenge to using implanted markers is determining the location of the markers
      in physical space after implantation. The A-mode ultrasonic technique described
      here is capable of determining the three-dimensional (3-D) location of small
      implanted cylindrical markers. Accuracy tests were conducted on a phantom
      representing a human head. The accuracy of the system was characterized by
      comparing the location of a marker analogue as determined with an optically
      tracked pointer and the location as determined with the ultrasonic localization.
      Analyzing the phantom in several orientations revealed a mean system accuracy of
      0.5 mm with a +/- 0.1-mm 95% confidence interval. These tests indicate that
      transcutaneous localization of implanted fiducial markers is possible with a high
      degree of accuracy.

PMID- 9581064
TI  - Numerical simulation of SAR and B1-field inhomogeneity of shielded RF coils
      loaded with the human head.
AB  - The finite-difference time-domain (FDTD) method is combined with the method of
      moments (MoM) to compute the electromagnetic fields of shielded radio-frequency
      (RF) coils loaded with an anatomically accurate model of a human head for high
      frequency magnetic resonance imaging (MRI) applications. The combined method can
      predict both the specific energy absorption rate (SAR) and the magnetic field
      (known as the B1 field) excited by any RF coils. Results for SAR and B1 field
      distribution, excited by shielded and end-capped birdcage coils, are calculated
      at 64, 128, 171, and 256 MHz. The results show that the value of SAR increases
      when the frequency of the B1 field increases and the B1 field exhibits a strong
      inhomogeneity at high frequencies.

PMID- 9581065
TI  - A cepstral method for analysis of acoustic transmission characteristics of
      respiratory system.
AB  - The generation and transmission process of transmitted sound signals (TSS) is
      analyzed and a mathematical model of TSS is established in this paper. The power
      cepstral characteristics of TSS are studied based on the mathematical model and a
      new analysis method of acoustic transmission of respiratory system using
      homomorphic processing technique is proposed. The experimental results show that
      the normal respiratory system has only one formant, while the abnormal
      respiratory system presenting lung consolidation has two formants and the second
      formant plays important role in that system. This new method is a simple and
      effective one.

PMID- 9581066
TI  - Influence of joint angle on the calibration and performance of EMG amplitude
      estimators.
AB  - Multiple-channel electromyogram (EMG) amplitude estimators incorporating temporal
      whitening filters and/or spatial uncorrelation filters contain a characterization
      of the EMG waveform (specifically, auto- and cross-correlation information) which
      may vary with joint angle. This paper reports on an experimental study which
      investigated the influence of joint angle on these EMG amplitude estimators. It
      was found that little or no relative improvement in estimator performance
      resulted from altering either temporal whitening or spatial uncorrelation filters
      as a function of joint angle. Also, the absolute performance level of these
      estimators did not vary with joint angle.

PMID- 9581067
TI  - Prediction of the sequence of optokinetic nystagmus eye movements reveals
      deterministic structure in reflexive oculomotor behavior.
AB  - Optokinetic nystagmus (OKN) is a reflexive eye movement with a characteristic
      pattern of alternating fast and slow phases (resembling a noisy sawtooth), but
      with significant variation in the timing and amplitude of its components. We
      attempt to predict the sequence of OKN fast and slow phases by embedding them in
      state space and forming local approximations to the resulting trajectories. There
      is significant predictability only in the sequence of fast phase starting and
      ending positions. This is presumably related to the desire of the oculomotor
      system to aim the eyes at a location in space where something important might be
      expected to appear, leading to a partially deterministic rule for generating the
      end points of the fast phases.

PMID- 9581068
TI  - Communicable diseases and fifty years of independence.

PMID- 9581069
TI  - Mitochondrial myopathies--a clinicopathological study.
AB  - Mitochondrial myopathies are heterogeneous group of clinical disorders that can
      affect multiple systems besides skeletal muscles. The mitochondrial abnormalities
      in the skeletal muscles are morphologically identified by the presence of
      characteristic Ragged-red fibers (RRF) in the cryostat sections of the muscle
      stained with modified Gomori's trichrome stain. In this retrospective study,
      clinical and histopathological features in six patients with mitochondrial
      myopathies have been analysed. The utility of histochemical methods in confirming
      the diagnosis of mitochondrial myopathy has been emphasised.

PMID- 9581070
TI  - A, B & H isoantigens in cervical lesions.
AB  - Expression of A, B and H isoantigens in cervical mucosa was demonstrated by
      specific red cell adherence test in 92 cervical lesions (40 chronic cervicitis,
      12 dysplasia and 40 carcinoma cervix). Eighty percent cases of chronic cervicitis
      showed a moderate reaction. On the contrary, in carcinoma cervix, 75% cases were
      found to be SRCA negative. In dysplasia, the intensity of red blood cell
      adherence was found to be directly related to the degree of cellular
      differentiation. Study of A, B and H isoantigens might help in deciding the
      prognosis of dysplasia and/or early detection of malignancy.

PMID- 9581071
TI  - Blood glucose and ischemic brain damage.
AB  - The effect of hyperglycemia on ischemic brain damage was studied in a rat model
      of incomplete ischemia. Incomplete ischemia was produced by permanent occlusion
      of one (either left or right) common carotid artery (CCA). Hyperglycemia was
      induced by intraperitoneal injection of 50% glucose, and same volume of
      physiological saline was injected in the controls 40 min before CCA ligation.
      Serum glucose level, at the time of vessel ligation, was 33.3 mMol/L. After CCA
      ligation, the rats were allowed to wake up and survive for upto 1 month.
      Perfusion-fixed brains were embedded in paraffin, subserially sectioned, and
      stained with haematoxylin-eosin/cresyl violet. Brain from sham-operated animals
      showed no damage neurons. Only mild neuronal damage was observed in saline pre
      treated rats in CA1 area. Histological examination 24 h after CCA occlusion
      revealed ischemic neuronal cell damage to be more extensive in hyperglycemic
      rats. Neuronal damage was found in the major brain structures vulnerable to
      several insults. Some of those damaged neurons recovered well, but presence of
      some damaged neurons at 1 month of recovery suggesting delayed recovery. The
      results indicate that increased blood glucose level (hyperglycemia) during brain
      ischemia exaggerates structural alterations and leads to delay in recovery.

PMID- 9581072
TI  - C-reactive protein and buffy coat smear in early diagnosis of childhood
      septicemia.
AB  - Out of 200 cases of septicemia in children (age group 0-14 years), 111 had
      positive C-Reactive Protein (CRP > 12 mg/l) and 84 were buffy coat smear
      positive. Blood culture was positive in 98 cases, with predominant organism being
      Klebsiella pneumoniae, followed by Staphylococcus aureus. CRP test showed 100%
      sensitivity and 87.3% specificity, while buffy coat smear showed 76.5%
      sensitivity and 91.2% specificity. As blood culture reports are not available
      before 48-72 hours, combination of CRP test and buffy coat smear examination will
      be very helpful in early diagnosis of childhood septicemia.

PMID- 9581073
TI  - Relation of mast cell, nerve and fibrosis in appendix.
AB  - The relationship of mast cells, nerves and fibrosis was studied in 50 cases of
      Appendix using simple histochemical technique. In the mucosa, the mast cell
      number was greater in the early stages of fibrosis. Both in the mucosa and
      submucosa mast cells were found closely associated with neural tissue. As the
      fibrosis increased this association between mast cells and neural tissue was
      retained only in the submucosa.

PMID- 9581074
TI  - A study on opportunistic enteric parasites in 80 HIV seropositive patients.
AB  - AIDS is characteristically associated with several opportunistic enteric
      protozoal infestations that cause chronic and at times fatal diarrhoeas. A study
      is undertaken to isolated opportunistic enteric parasites in 80 HIV seropositive
      patients. An attempt is made to correlate and signify the presence of coexistent
      oral candidosis and enteric pathogens.

PMID- 9581075
TI  - A simple device for embalming cadavers.
AB  - A simple design of a mobile embalming unit is presented that offers better
      quality embalming and is fairly economical. The technique is faster and
      consistently more reliable than the conventional gravity aided embalming.

PMID- 9581076
TI  - Serology and immunoglobulin profile in rheumatoid arthritis.
AB  - One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non
      rheumatoid cases suffering from various other diseases and 40 healthy individuals
      were investigated for the presence of rheumatoid factor, quantitation of serum
      immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex
      agglutination test of serum for rheumatoid factor showed 56.6% positivity in
      rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum
      immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in
      cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group
      of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and
      4.4% cases of rheumatoid arthritis who had severe underlying disease. In non
      rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed
      rheumatoid factor and that too in an insignificant titre (less than 1:20).
      Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It
      has been observed that RF appears first in synovial fluid and it may take several
      months to a year to attain detectable level in serum.

PMID- 9581077
TI  - Enhanced detection of herpes simplex virus from ocular specimens of herpetic
      keratitis patients.
AB  - Corneal scrapings collected from 70 patients were used to assess the diagnostic
      value of indirect immunofluorescence (indirect IF) procedure in comparison with
      routine virus culture (RVC) for the diagnosis of Herpes simplex virus induced
      keratitis (HSK). Virus specific antigen was detected by indirect IF in 22
      (31.42%) cases. In contrast, only 20% (14) of the cases had positive viral
      isolation which sometimes took as long as a week to show a cytopathogenic effect
      (CPE). It is concluded that antigen detection by indirect IF is a rapid, specific
      and sensitive technique for demonstrating HSV-1 antigen in corneal scrapings from
      HSK patients and a useful laboratory tool not only for diagnosing HSK but also
      for monitoring efficiency of anti HSV treatment for HSK.

PMID- 9581078
TI  - Changing patterns and re-distribution of antigen in poorly differentiated
      carcinomas: its implications in tumour diagnosis.
AB  - The variability of expression of tumour-associated antigens via either antigenic
      heterogeneity or antigenic modulation presents a basic problem in
      immunohistochemical diagnosis of poorly/undifferentiated tumours. This work was
      designed to study antigenic expression on human resected epithelial tumours by a
      panel of most widely used antibodies (EMA, CEA, AUAI & Cytokeratin) in relation
      to tumour differentiation and polarization. It was observed that poorly
      differentiated carcinoma with loss of polarity show homogeneous membrane staining
      (with antibodies against EMA, CEA & AUAI) in contrast to either apical (luminal)
      or basolateral membrane staining in well differentiated counterparts. Biochemical
      studies have shown that apical and basolateral epithelial cell membrane domains
      have a characteristic set of glycoproteins. Tight junctions are essential for
      maintaining this functional polarization. It was concluded that structural and
      functional abnormalities of tight junctions in poorly differentiated carcinomas
      results in loss of polarity with progressive invasion of the cell surface by
      antigenic glycoprotein and resultant homogeneous individual cell antigenic
      expression in poorly differentiated carcinomas. This study demonstrates that
      antigenic expression on tumour cells is not static, but dynamic and heterogeneity
      of antigenic expression may well be due to biological factors such as spatial
      configuration of the lesion.

PMID- 9581079
TI  - The role of Gardnerella vaginalis in nonspecific vaginitis in intra uterine
      contraceptive device users.
AB  - Two Hundred Forty patients who had Intra Uterine Contraceptive Device (IUCD) and
      manifested of nonspecific vaginitis were investigated for the presence of G.
      vaginalis. Pure growth of this organism was obtained in 14(5.8%) cases while
      116(48.3%) cases showed this organism in association with other organisms e.g.
      Esch. coli (11.7%), Klebsiella (9.2%), Candida (9.2%), Strept. faecalis (7.3%),
      Proteus species (5.8%) and Staph. albus (5%).

PMID- 9581080
TI  - Autopsy study of patients dying of bleeding diathesis.
AB  - Ten thousand & thirty seven autopsies performed from the year 1982 to 1992 were
      studied retrospectively, to find out the number of deaths due to bleeding
      diathesis. Eighty-seven (0.87%) patients died due to bleeding diathesis, out of
      which haemolytic uraemic syndrome (HUS) was seen in 9 cases (10.34%),
      disseminated intravascular coagulation (DIC) in 67 cases (77.01%) & 11 cases were
      grouped as miscellaneous. Martius scarlet blue stain was carried out to
      demonstrate fibrin & depending on the number of thrombi in the glomerulus & blood
      vessels, the lesions were graded as mild, moderate or severe. Kidney was the most
      common organ involved in all groups of bleeding diathesis. In DIC kidney & lung
      involvement was almost equal.

PMID- 9581081
TI  - Neonatal hepatitis--an autopsy study of 14 cases.
AB  - Fourteen autopsy cases of neonatal hepatitis have been studied. Of these seven
      cases were due to infections viz.: cytomegalovirus infection (four cases),
      probable cases of congenital syphilis (two cases) and neonatal herpes (one case).
      The remaining seven cases were of Idiopathic Neonatal Hepatitis (INH) with giant
      cell change in six cases. Even in these cases (INH) there was a high index of
      suspicion of intrauterine or acquired infection in view of severe mononuclear
      inflammation in the pancreas, alimentary tract and lungs. Most of these neonates
      with INH had low birth weight and two were preterm pointing towards a prenatal
      insult. The orcein stain and Periodic Acid Schiff (PAS) with diastase in all the
      cases were negative making hepatitis B virus infection and infinity 1 antitrypsin
      deficiency less likely. These autopsies represent the tip of the iceberg and only
      the severe cases of infection. The fatal outcome could have been prevented by
      maternal screening for infections and earlier clinical diagnosis.

PMID- 9581082
TI  - Cytohormonal evaluation of vaginal smears by phase contrast microscopy with
      special reference to progesterone deficiency pattern during early pregnancy as
      predictor of abortion.
AB  - Cytohormonal profile of unstained vaginal smears were studied under phase
      contrast microscope to define various cell morphologies in detail and build up of
      smear pattern serially in various stages of menstrual cycle and first trimester
      of pregnancy. The findings were correlated clinically and found comparable to
      Papanicolaou stained smears. The maturation index was calculated more objectively
      by phase contract microscopy because of the refractile appearance of the pyknotic
      nuclei of superficial cells. The prognostication of abortion was done by
      combining abnormal maturation index and the presence of syncytiotrophoblasts in
      vaginal smears. Under phase contrast microscope, the sensitivity of abnormal
      smear was 87.5%, the specificity was 95%, the positive predictive value was
      96.55% and the overall accuracy was 90% as compared to positive Papanicolaou
      smear whose sensitivity though 93%, had low specificity of 50% only. Phase
      contrast study appears to offer certain distinct advantage over the conventional
      light microscopy for quick, comprehensive and quantitative assessment of the
      study material. It allows the physician to detect changes in the material
      obtained from the patients without detour of laboratory fixation and staining. It
      is technically easy as errors in interpretation due to unsatisfactory fixation,
      staining and artefacts are obviated. Thus phase contrast microscopy offers an
      alternative and easy method of cytohormonal evaluation of wet and unstained
      smears.

PMID- 9581083
TI  - Aspiration cytologic diagnosis in clinically unsuspected leprosy--a case report.

PMID- 9581084
TI  - Intraperitoneal abscess in a new born secondary to Klebsiella septicaemia--a case
      report.
AB  - A five day old female baby was admitted with distension of abdomen since birth
      and nonbilious vomiting, fever of one day duration. Blood culture grew Klebsiella
      pneumoniae. Abdominal exploration revealed thick walled cavity containing
      purulent fluid grew klebsiella pneumoniae which was sensitive to various
      antibiotics including gentamycin. The child was treated with injection gentamycin
      and ceftazidime. The child had uneventful recovery and is doing well 3 years post
      operatively.

PMID- 9581085
TI  - Papillary carcinoma of the male breast diagnosed by fine needle aspiration
      cytology.
AB  - A 57-year old male presented with a left breast mass, the fine needle aspiration
      cytology revealed characteristic cytomorphological features of papillary
      carcinoma of the breast. In our knowledge this is a second reported case of
      papillary carcinoma of male breast diagnosed by the fine needle aspiration
      cytology. Cytomorphological and histopathological features of the case are
      described with literature on cytological features of papillary carcinoma and
      carcinoma of male breast is briefly reviewed.

PMID- 9581086
TI  - Multiple primary visceral malignancy--a review with report of two cases.
AB  - Multiple primary cancers are being reported with increasing frequency in recent
      years, the frequency varying from 0.3 to 4.3% in different studies. A combination
      of primary cancer of larynx and lung is the most common followed by malignant
      neoplasm involving lip-larynx, skin-larynx, skin-lung, breast-ovary and breast
      endometrium. Two interesting cases of rare combinations of primary cancers are
      being presented. In the first case primary adenocarcinoma of the gall bladder was
      associated with appendiceal adenocarcinoma. In the second case primary malignant
      papillary serous cystadenocarcinoma of right ovary and squamous cell carcinoma of
      cervix uteri were found.

PMID- 9581087
TI  - Neurofibromatosis of the colon: an unusual manifestation of von Recklinghausen's
      diseases--a case report.
AB  - Multiple neurofibromas arising in nerves are well established features of von
      Recklinghausen's disease. However, significant involvement of the
      gastrointestinal tract, especially the colon, is a rare entity. We hereby report
      a case of colonic neurofibromatosis.

PMID- 9581088
TI  - Troponin--a promising marker for myocardial injury.

PMID- 9581089
TI  - Anti tubercular activity of garlic oil.

PMID- 9581090
TI  - Birth language: a renewed consciousness.

PMID- 9581091
TI  - Midwifery management of pain in labor. The CNM Data Group, 1996.
AB  - Joint data collection by nine nurse-midwifery practices in the United States
      permitted a description of pain management practices with intrapartum patients.
      Observational data are reported for healthy gravidas at term (N = 4,171). A wide
      variety of techniques for pain management, including both pharmacologic and
      nonpharmacologic methods, were used. High prevalence modalities were paced
      breathing (used by 55.2% of this clinical sample), activity and position change
      (42.4%), narcotics (30.0%), and epidurals (18.7%). Paced breathing plus narcotics
      was the most common combination. Variations are reported for subgroups of women
      according to age, parity, race/ethnicity, education, insurance, marital status,
      activity in labor, and type of delivery. The only methods associated with a
      lowered rate of spontaneous delivery were epidurals and intrathecal narcotics.

PMID- 9581092
TI  - Bacterial vaginosis and preterm birth: a comprehensive review of the literature.
AB  - Preterm low birth weight is the major determinant of infant morbidity and
      mortality. Numerous studies have linked bacterial vaginosis (BV) with preterm
      birth and low birth weight (LBW), especially among black women. This article
      reviews the published literature to provide clear evidence that BV is an
      independent risk factor for preterm birth and LBW. Pregnant black women are
      especially at risk, having nearly three times the level of BV as pregnant white
      women. Compounding the problem is the fact that half the population of women with
      BV are asymptomatic, and current standard antenatal procedures do not provide for
      screening for BV. By reviewing BV treatment literature, this article also
      provides evidence that treatment for BV is effective and that the identification
      and treatment of BV in pregnant women can lead to substantial reduction in the
      high rates of preterm birth and LBW.

PMID- 9581094
TI  - Practical approaches for estimating prepregnant body weight.
AB  - Measurements of prepregnant body weight have important research and clinical
      applications. In practice, however, they are not always recorded; even when they
      are, this information is not always readily available. For this reason,
      researchers and clinicians have to rely on retrospective estimates of prepregnant
      weight, which can be estimated using: 1) maternal self-reports, 2) retrospective
      extrapolation, or 3) standardized estimates that correct for weight gained during
      early pregnancy. The aim of the present study was to examine the relative merits
      of these three approaches. Maternal self-reports tend to be unreliable and
      biased, being influenced by a variety of sociodemographic characteristics that
      generally underestimate true prepregnant body weight. Estimates of prepregnant
      weight based on retrospective extrapolation are vulnerable to measurement error,
      transient fluctuations in body weight, and incorrectly assume that the rate of
      weight gain is constant throughout pregnancy. Standardized estimates that correct
      for weight gained during early pregnancy incorrectly presume that there is little
      interindividual variation in gestational weight gain and that weight gain is
      similar for each woman in consecutive pregnancies. Because none of these
      techniques can provide a precise measure of prepregnant weight, researchers have
      little alternative but to recruit and weigh women before they become pregnant,
      although measurements of body weight recorded during the first trimester of
      pregnancy may provide a reasonable indication of prepregnant weight. For
      clinicians, self-reports of prepregnant weight or measurements recorded early in
      pregnancy are probably sufficiently accurate for practical purposes whenever
      recent, accurate measurements of prepregnant weight are unavailable.

PMID- 9581093
TI  - Use of prenatal services by Hispanic women in San Diego County. A comparison of
      urban and rural settings.
AB  - The purpose of this study was to investigate patterns of prenatal care use among
      urban and rural Hispanic women in San Diego County, California. A cohort study of
      Hispanic women delivering at one of five San Diego County hospitals between July
      1991 and January 1992 was conducted (N = 587). Data were collected by in-person
      interview and medical record abstraction. Logistic regression was used to
      identify variables associated with late entry into prenatal care, while
      simultaneously adjusting for important confounding variables. Three factors were
      found to be significantly associated with late entry into prenatal care. Women
      who resided in urban areas were two times more likely to enter prenatal care late
      as compared to women who lived in rural areas (odds ratio = 2.11; 95% confidence
      intervals (CI) = 1.12, 4.0). Women who reported not having initially "wanted" the
      pregnancy were 2.2 times more likely to enter prenatal care late (95% CI = 1.05,
      4.59). The risk of entering prenatal care late increased by 20% for each
      additional barrier to care that was reported (95% CI = 1.09, 1.34). Results
      indicate that timely entry into prenatal care may be improved among San Diego
      Hispanic women by targeting specific barriers to prenatal care identified in this
      study and by providing greater family planning assistance to this population to
      decrease unwanted pregnancies.

PMID- 9581095
TI  - Direct entry midwifery education. Evaluation of program innovations.
AB  - During the 1996-1997 academic year, the State University of New York Health
      Science Center at Brooklyn, in partnership with North Central Bronx Hospital,
      implemented the first direct entry (DE) midwifery education program to be
      preaccredited by the American College of Nurse-Midwives. Five DE midwifery
      students were admitted and graduated. During their one-year course of studies,
      these students were provided supplementary didactic and clinical instruction in
      the medical sciences and basic health skills in addition to the identical course
      of midwifery studies offered to their registered nurse-student peers. The
      experience of students and faculty during this first year was that there was no
      significant difference in academic performance between the DE and nurse-midwifery
      students. Moreover, once oriented to the clinical environment, DE students
      progressed through the clinical practicums, and acquired entry-level midwifery
      skills, at a pace equivalent to that of their nurse peers and consonant with all
      expectations of safe practice. In addition, the Basic Health Skills and
      Integrated Medical Science course offerings served as effective instructional
      supplements to the curriculum by providing DE students with an opportunity to
      equalize their knowledge base with that previously acquired by registered nurse
      prepared students; an unanticipated discovery was that some nurse-midwifery
      students could equally benefit from enrollment in these courses.

PMID- 9581096
TI  - Intrapartum hypertension in a low-risk obstetric population.
AB  - Hypertension is one of the more serious medical problems requiring special
      attention during labor. Clinical midwifery data were used to determine the
      incidence of and risk factors for intrapartum hypertension in a low-risk
      population of women who received care from certified nurse-midwives. Descriptive
      statistics are reported for demographic and clinical variables. Nulliparity and
      young maternal age were two important risk factors for onset of hypertension in
      labor. Body mass index, weight gain in pregnancy, and advanced maternal age,
      however, were not predictors. The impact of cultural factors and the style of
      care on the modification of risk conditions warrants further investigation.

PMID- 9581097
TI  - Mentoring and job satisfaction. Perceptions of certified nurse-midwives.
AB  - The purpose of this study was to investigate the relationship between mentoring
      and job satisfaction among recently certified nurse-midwives. The Demographic
      Data Questionnaire, Job Satisfaction Survey, and Quality of Mentoring Tool were
      mailed to all first-year eligible members (N = 466) of the American College of
      Nurse-Midwives (ACNM). A total of 317 surveys (68%) were included in the
      analysis. Sixty-five percent (n = 208) have had a mentor. Twenty-six (8%) had
      participated in the ACNM Mentoring Program and 33 (10%) had participated in a
      student mentoring program other than the ACNM Mentoring Program. The most
      frequently identified qualities of the mentoring relationship were model,
      supporter, envisioner, and investor. Eighty-one percent (n = 249) reported that
      they were satisfied with their current job. There was no significant relationship
      between stated job satisfaction and participation in a mentoring relationship. A
      significant, but low, correlation was found between stated job satisfaction and
      the quality of the mentoring relationship (r = .16, P = .03) and between scores
      on the Job Satisfaction Survey and Quality of Mentoring Tool (r = .14, P = .04).

PMID- 9581098
TI  - Accuracy of the Ovulon fertility monitor to predict and detect ovulation.
AB  - The purpose of this pilot study was to correlate the three biologic markers of
      the Ovulon fertility monitor (a long-term predictive peak about 6 days before
      ovulation, a short-term predictive peak about 1 day before ovulation, and a nadir
      at the time of ovulation) with the peak in cervical mucus and the luteinizing
      hormone (LH) surge in the urine. Ten volunteer subjects (mean age 30.2 years)
      monitored their cervical-vaginal mucus, the surge of LH in the urine with a home
      assay test, and their vaginal electrical readings (with Ovulon monitors) on a
      daily basis for one to four menstrual cycles. In 19 of the 21 cycles that
      indicated a LH surge, there was a strong positive correlation between the LH
      surge and the peak of cervical-vaginal mucus (r = 0.96, P < or = .01), and
      between the LH surge and both the Ovulon nadir and Ovulon short-term predictive
      peak (r = 0.84, P < or = .01), and a modest positive correlation between the long
      term Ovulon predictive peak and the LH surge (r = 0.62, P < or = .01). The time
      of optimal fertility as determined by the peak in cervical mucus, the LH surge,
      and the Ovulon was similar. The Ovulon has potential as a reusable device to help
      women determine their fertile period.

PMID- 9581099
TI  - Physician- and midwife-attended home births.

PMID- 9581100
TI  - Pregnancy interruption using mifepristone (RU-486): a new choice for women in the
      USA.

PMID- 9581101
TI  - Early-onset group B strep infection in newborns: prevention and prophylaxis.

PMID- 9581102
TI  - Induction of labor in the nineties: conquering the unfavorable cervix.

PMID- 9581103
TI  - Persistence of penicillin G benzathine in pregnant group B streptococcus
      carriers.

PMID- 9581104
TI  - Delayed entry into prenatal care: effect of physical violence.

PMID- 9581105
TI  - Risk for neural tube defect-affected pregnancies among women of Mexican descent
      and white women in California.

PMID- 9581107
TI  - Differing birth weight among infants of U.S.-born blacks, African-born blacks,
      and U.S.-born whites.

PMID- 9581106
TI  - "I gotta push: please let me push!" Social interactions during the change from
      first to second stage labor.

PMID- 9581109
TI  - Managed care reform passes Senate: pressure moves to House.

PMID- 9581108
TI  - Opportunities for prevention of perinatal group B streptococcal disease: a
      multistate surveillance analysis.

PMID- 9581111
TI  - CAT Fund Advisory Board offers recommendations.

PMID- 9581110
TI  - State society takes lead opposing E&M guidelines.

PMID- 9581112
TI  - State society urges AMA to pursue ICD-9 changes.

PMID- 9581113
TI  - More government intrusion into patient care.

PMID- 9581116
TI  - Fraud and abuse gaining attention amid national E&M guideline controversy.

PMID- 9581115
TI  - Are we doing the most for our diabetic patients?

PMID- 9581117
TI  - Choosing litigation is a balancing act.

PMID- 9581118
TI  - Promoting healthier communities.

PMID- 9581119
TI  - Managed care reform ... what does it mean for patients?

PMID- 9581120
TI  - Center offers first OTC drug/conditions chart.

PMID- 9581121
TI  - What to expect at your deposition: a guide for physicians and health care
      professionals.

PMID- 9581123
TI  - The visuospatial sketchpad for mental images: testing the multicomponent model of
      working memory.
AB  - In the model of Baddeley (Working Memory, Oxford University Press, Oxford, 1986),
      one function of the visuospatial sketchpad (VSSP) component of working memory is
      to allow the processing of mental images. Properties of the VSSP were
      investigated by means of the usual dual-task paradigm (to search for interference
      from the other components of working memory, i.e., the articulatory loop and the
      central executive), applied to three distinct subprocesses of mental imagery
      (Kosslyn, 1994 Image and Brain. MIT Press, Cambridge, MA): image generation
      (Experiment 1), image maintenance (Experiment 2), and image rotation (Experiment
      3). First, in the control condition (no interference task) of each experiment, we
      replicated the effects of stimulus or task complexity already reported. Second,
      no interference from the articulatory loop was observed. Third, maintenance of
      images appeared free from any interference. And fourth, generation and rotation
      tasks were interfered to a greater extent by the central executive than by the
      involvement of the VSSP in a secondary task. These observations (a) support the
      dissociation between the articulatory loop and the VSSP, (b) suggest an important
      use of central attentional resources in the generation and rotation of mental
      images, (c) would support the distinction between visual and spatial components
      in the structure of working memory, and (d) suggest the dissociation of the VSSP
      into two subcomponents: a passive visuospatial store and an active device for
      recapitulating visuospatial information.

PMID- 9581122
TI  - Is visual anticipation of collision during self-motion related to perceptual
      style?
AB  - We have previously shown that during self-motion in car driving situations, the
      perception of another car's trajectory relies both on global visual information
      such as the optical flow field, and on local visual information such as the
      optical motion of the other car and the relative optical motion of the other car
      with respect to fixed elements in the environment. Here, we studied the
      environmental factors that contribute to perceptual judgements in relation to the
      observer's perceptual style (visual-field dependence vs. visual-field
      independence). In an experiment, observers were presented with visual scenes
      corresponding to the curvilinear self-motion of a driver approaching an
      intersection where another vehicle was arriving perpendicularly. The factors
      manipulated were the presence or absence of a spatial reference point (road sign
      near the intersection), environmental complexity ("road" or "spot" scenes), and
      the degree of field dependence/independence. Nine field-independent (FI) subjects
      and seven field-dependent (FD) subjects were asked to predict whether the other
      vehicle would reach the intersection before or after they would. Their responses
      were analyzed. Overall, subjects' judgements were more accurate with road
      environments and with a road sign, suggesting that the relative motion of the
      other vehicle with respect to fixed elements in the environment provides
      additional useful information. FI subjects were significantly more accurate than
      FD subjects, suggesting that the former are better at picking up relevant dynamic
      information in a complex environment.

PMID- 9581124
TI  - What makes people study more? An evaluation of factors that affect self-paced
      study.
AB  - Allocation of study time across items was investigated in three experiments.
      According to the norm-affects-allocation hypothesis, when studying an item, a
      person changes the sought-after degree of learning for the item (called the norm
      of study) in an attempt to achieve task goals. As the norm of study is increased,
      more time will be allocated for study. This hypothesis was evaluated by having
      people pace their study of items for an eventual test of recall. As predicted,
      study time was greater (a) when points awarded for recalling an item increased,
      (b) when instructions emphasized mastering each item rather than quickly learning
      each item, (c) when points deducted for each second of study decreased, and (d)
      when the likelihood an item would be on the test increased. Also, although
      allocating more study time was usually accompanied by an increase in eventual
      recall, under several conditions people's allocation of study time appeared sub
      optimal. Discussion focuses on current theory of self-paced study and people's
      apparent sub-optimal allocation of study time.

PMID- 9581125
TI  - Mental imagery yields stimulus-response compatibility.
AB  - The present paper provides evidence for stimulus-response (S-R) compatibility
      effects in visual mental images. In two experiments subjects either studied a
      simple map (Experiment 1) or read a verbal description of the same map
      (Experiment 2), and then responded after generating a mental image of the
      presented information. Responses were made in a crossed-hand and in an uncrossed
      hand manner, and the S-R arrangements were compatible and incompatible. In both
      experiments response latencies were found to be faster for compatible than for
      incompatible S-R mappings, and the crossed-hand condition resulted in increased
      response latencies relative to the uncrossed-hand condition. The findings are
      discussed with respect to the processing mechanisms involved in imagery and
      perception.

PMID- 9581126
TI  - Auditory stress effects on preparation and execution of graphical aiming: a test
      of the neuromotor noise concept.
AB  - Effects of physical and mental stress, on the preparation and execution of a
      psychomotor task were studied to test the applicability of the neuromotor noise
      concept (Van Gemmert and Van Galen, 1997) as an explanation of stress effects.
      Central to this notion is that both physical stress and mental load raise
      neuromotor noise levels in the human information processing system. It is
      proposed that increased levels of neuromotor noise lead to decreased processing
      times during task preparation (activation effect), decreased or increased
      reaction times during task initiation, depending on task difficulty (impoverished
      signal-to-noise effect) and increased limb stiffness during task execution
      (biomechanical filtering effect). To test these predictions, an experiment was
      conducted in which two types of auditory stressors, physical stress and mental
      load, were manipulated across the stages of preparation, initiation, and
      execution of a graphical aiming task. The results confirmed the notion that the
      neuromotor noise concept is a tenable approach to explain the effects of stress
      on human performance.

PMID- 9581128
TI  - Health tips. Gearing up for golf.

PMID- 9581127
TI  - Hip fractures. Surgery is usually effective, but recovery takes time.

PMID- 9581130
TI  - Additional evidence that walking has health benefits.

PMID- 9581129
TI  - More preventive screenings now covered by Medicare.

PMID- 9581131
TI  - Varicose veins. New techniques allow outpatient treatment.

PMID- 9581132
TI  - Near-death experiences. Being supportive can help.

PMID- 9581133
TI  - Trans fat. Another artery-clogger?

PMID- 9581134
TI  - Can you tell me about St. John's wort? I've been depressed and wonder if it would
      be safe to take.

PMID- 9581135
TI  - Does the new pill to treat baldness really work?

PMID- 9581136
TI  - Measurement of cardiac troponin T is an effective method for predicting
      complications among emergency department patients with chest pain.
AB  - STUDY OBJECTIVES: To determine the test performance characteristics of serum
      cardiac troponin T (cTnT) measurement for diagnosis of acute myocardial
      infarction (AMI), and to determine the ability of cTnT to stratify emergency
      department patients with chest pain into high- and low-risk groups for cardiac
      complications. METHODS: We conducted a prospective observational cohort study
      with convenience sampling in a tertiary care, urban ED. The study sample
      comprised 667 patients presenting to the ED with a complaint of chest pain or
      other symptoms suggesting acute ischemic coronary syndrome (AICS). Patients were
      assigned to different blood sampling protocols for cTnT therapy on the basis of
      their ECG at presentation: nondiagnostic for AMI at 0, 3, 6, 9, 12, and 24 hours
      after ED presentation; or ECG diagnostic for AMI at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,
      12, 18, and 24 hours after ED presentation. RESULTS: Of 667 patients, 34 had AMI
      diagnosed within 24 hours of ED arrival. Using a .2 microgram/L discrimination
      level for cTnT, sensitivity for AMI within 24 hours of ED arrival was 97% (95%
      confidence interval, 91.4% to 99.9%), and specificity was 92% (89.8%-94.1%). When
      the effects of age, race, sex, and creatine kinase-MB isoenzyme subunit test
      results were controlled, a patient with cTnT of .2 microgram/L or greater was 3.5
      (1.4 to 9.1) times more likely to have a cardiac complication within 60 days of
      ED arrival than a patient with a cTnT value below .2 microgram/L. CONCLUSION:
      Measurement of cTnT will accurately identify myocardial necrosis in patients
      presenting to the ED with possible AICS. Elevated cTnT values identify patients
      at increased risk of cardiac complications.

PMID- 9581137
TI  - Early echocardiography can predict cardiac events in emergency department
      patients with chest pain.
AB  - STUDY OBJECTIVE: Accurate diagnosis in emergency department patients with
      possible myocardial ischemia is problematic. Two-dimensional echocardiography has
      a high sensitivity for identifying patients with myocardial infarction (MI);
      however, few studies have investigated its diagnostic ability when used acutely
      in ED patients with possible myocardial ischemia. Therefore we investigated the
      ability of ED echocardiography for predicting cardiac events in patients with
      possible myocardial ischemia. METHODS: Echocardiography was performed within 4
      hours of ED presentation in 260 patients with possible myocardial ischemia, and
      was considered positive if there were segmental wall motion abnormalities or the
      ejection fraction was less than 40%. ECGs were considered abnormal if there was
      an ST-segment elevation or depression of greater than or equal to 1 mm, or
      ischemic T-wave inversion. Cardiac events included MI and revascularization.
      RESULTS: Of the 260 patients studied, 45 had cardiac events (23 MI, 19
      percutaneous transluminal angioplasty, 3 coronary bypass surgery). The
      sensitivity of echocardiography for predicting cardiac events was 91% (95%
      confidence interval 79% to 97%]), which was significantly higher than the ECG
      (40% [95% CI 27% to 55%]: P < .0001), although specificity was lower (75% [95% CI
      69% to 81%] versus 94% [95% CI 90% to 97%]; P < .001). Addition of the
      echocardiography results to baseline clinical variables and the ECG added
      significant incremental diagnostic value (P < .001). With use of multivariate
      analysis, only male gender (P < .03, odds ratio [OR] 2.4 [1.1 to 5.3]), and a
      positive echocardiographic finding (P < .0001, OR 24 [9 to 65]) predicted cardiac
      events. Excluding patients with abnormal ECGs (N = 30) did not affect sensitivity
      (85%) or specificity (74%) of echocardiography. CONCLUSION: Echocardiography
      performed in ED patients with possible myocardial ischemia identifies those who
      will have cardiac events, is more sensitive than the ECG, and has significant
      incremental value when added to baseline clinical variables and the ECG.

PMID- 9581139
TI  - Critical pathway for the emergency department management of acute asthma: effect
      on resource utilization.
AB  - STUDY OBJECTIVE: To determine the effect of a critical pathway on resource
      utilization in asthmatic patients. METHODS: The study combined a prospective
      analysis of 149 patients with asthma treated by a pathway protocol with a
      retrospective analysis of 97 patients with asthma treated by conventional means.
      The setting was a community hospital. RESULTS: Among patients treated by
      protocol, oxygen use declined by 19% (P = .001), handheld nebulizer treatments by
      33% (P = .001), saline locks by 15% (P = .011), and intravenous steroid
      administration by 13% (P = .034). There was an increase in the use of metered
      dose inhalers with spacer by 64% (P = .001) and oral steroids by 18% (P = .027).
      CONCLUSION: A critical pathway, based primarily on national guidelines, can be an
      effective means of treating asthma patients in terms of resource utilization.

PMID- 9581138
TI  - Adrenal function and physiologic stress during acute asthma exacerbation.
AB  - OBJECTIVE: Adrenal function in stable asthmatics has been extensively studied.
      The purpose of this study was to determine the effect of asthma exacerbation on
      adrenal function. METHODS: We studied an observational cohort, convenience sample
      of patients at a university-affiliated county hospital. Adult patients with
      asthma who were not steroid-dependent and who presented to the emergency
      department because of their asthma comprised the study group. All patients were
      examined and pulmonary function tests were performed. Blood samples for
      determination of initial cortisol levels were obtained, followed by the
      administration of .25 mg cosyntropin intramuscularly. Standard therapy with
      aerosolized albuterol was then initiated. Plasma cortisol levels were measured 30
      and 60 minutes later. Steroid therapy was withheld until completion of the rapid
      cosyntropin stimulation test. RESULTS: A total of 74 patients participated; 64%
      (47) were women. The range of pretreatment FEV1 was from 10% predicted to 74%
      predicted. The range of cortisol levels on presentation was from 1.6
      micrograms/dL to 35.8 micrograms/dL. Twelve patients had initial cortisol levels
      greater than 20 micrograms/dL, a level indicative of physiologic stress. Four
      patients had initial cortisol levels greater than 30 micrograms/dL. Mean plasma
      cortisol levels at 0, 30, and 60 minutes were 13.7 micrograms/dL (+/- 7.2
      micrograms/dL), 28.7 micrograms/dL (+/- 7.4 micrograms/dL), and 33.0
      micrograms/dL (+/- 8.2 micrograms/dL). We found an association between evidence
      of physiologic stress and severe airflow obstruction (P < .03) but no linear
      correlation (r = -.15). CONCLUSION: Few patients with asthma have adrenal
      suppression on presentation. Asthma exacerbation does not provoke a physiologic
      stressor response in most asthmatic patients.

PMID- 9581140
TI  - Ventilatory strategies affect gas exchange in a pig model of closed-chest cardiac
      compression.
AB  - STUDY OBJECTIVE: To identify the arterial and mixed venous blood gas changes
      caused by different ventilatory strategies during resuscitation from ventricular
      fibrillation in a pig model of closed-chest cardiac compression. METHODS: A
      prospective randomized animal study was performed using 27 domestic pigs (body
      weight, 30 to 35 kg). Pentobarbital-anesthetized pigs were assigned to receive
      one of three treatments: (1) chest compression without assisted ventilation (n =
      8), (2) assisted ventilation with room air (n = 8), and (3) assisted ventilation
      with 100% oxygen (n = 8). A fourth group, with the airway completely blocked, was
      added at the end of the experiment (n = 3). After instrumentation, the ventricles
      were fibrillated, and chest compression was begun 30 seconds after fibrillation
      with the use of the Thumper Mechanical CPR system (Michigan Instruments).
      Arterial and mixed venous blood gas samples were collected at 1, 3, 10, and 20
      minutes of resuscitation. Defibrillation was attempted after the 20-minute sample
      was taken. RESULTS: Fibrillation followed by chest compression alone caused a
      significant drop in arterial and mixed venous partial pressure of oxygen (PO2)
      and a significant increase in arterial and mixed venous partial pressure of
      carbon dioxide (PCO2). Compared with the chest compression only, ventilation with
      room air significantly increased arterial and mixed venous PO2 and decreased
      arterial and mixed venous PCO2. Ventilation with 100% oxygen further increased
      arterial and mixed venous PO2 but did not affect PCO2, when compared with room
      air ventilation. The only successful defibrillations (3 animals) occurred in the
      group receiving 100% oxygen. CONCLUSION: This study indicates that passive air
      movement during chest compression does not allow physiologically significant
      pulmonary gas exchange and that room air ventilation alone is not sufficient to
      maintain mixed venous PO2.

PMID- 9581142
TI  - 1997 National Asthma Education and Prevention Program guidelines: a practical
      summary for emergency physicians.
AB  - Numerous clinical guidelines have been promoted to help improve the management of
      acute injury and illness. In November 1997, the National Asthma Education and
      Prevention Program released the final version of its comprehensive second Expert
      Panel Report, designed to distill scientific advances in asthma care and provide
      a set of practical tools to help guide clinician and patient decisions. The
      panel's recommendations for acute asthma care stress the use of the objective
      measures of pulmonary function to assess severity, aggressive inhaled beta 2
      agonist therapy, early systemic corticosteroid administration, and early
      disposition decisions. This article provides a focused overview of the 146-page
      document and highlights aspects of the new guidelines of particular importance to
      emergency physicians.

PMID- 9581141
TI  - Use of tube condensation as an indicator of endotracheal tube placement.
AB  - STUDY OBJECTIVE: To determine whether condensation on the inner surface of the
      endotracheal tube (vapor trail) is a reliable indicator of intratracheal
      placement. METHODS: Twenty-seven separate experiments were conducted on 10
      conditioned, mongrel dogs weighing 15 to 20 kg each. After induction of
      anesthesia, an endotracheal tube was placed in the trachea under direct
      visualization. A second, identical endotracheal tube was then placed in the
      esophagus. An attending emergency physician, blinded to tube placement, then used
      a bag-valve apparatus to manually ventilate each endotracheal tube in turn. Five
      ventilations were performed on each tube, and the presence or absence of
      condensation on the inner surface of the tube was recorded. A second physician,
      blinded both to tube placement and to the actions of the first assessor, then
      repeated the ventilation and assessment of both tubes. RESULTS: Vapor trail was
      observed in 27 (100%) of 27 endotracheal tubes correctly placed in the trachea
      (95% confidence interval [CI], 90% to 100%) and in 23 (83%) of 27 tubes placed in
      the esophagus (95% CI, 66% to 96%). Physicians concurred in all cases. Absence of
      vapor trail was 15% sensitive (95% CI, 4% to 34%) for indicating incorrect
      (esophageal) tube placement. CONCLUSION: In this model, condensation on the inner
      surface of the endotracheal tube was common after placement within the esophagus.
      If these results are confirmed in human studies, the presence of a vapor trial
      should not be used as a clinical indicator of correct endotracheal tube
      placement.

PMID- 9581143
TI  - Advances, opportunities, and the new asthma guidelines.
AB  - A main tenet of the National Asthma Education and Prevention Program's approach
      is to integrate proper management of acute asthma into overall asthma care.
      Accordingly, we maintain that emergency physicians should be aware of emerging
      chronic management strategies, especially newer treatment regimens, so as to
      understand pre-ED treatments, provide optimum ED care, and make appropriate
      prescriptions and referral on discharge. This commentary discusses limitations to
      the new guidelines and identifies important areas for further study.

PMID- 9581144
TI  - A study of the workforce in emergency medicine.
AB  - STUDY OBJECTIVE: Emergency medicine has progressed significantly since its
      initial recognition as a medical specialty. Relatively little factual information
      is known, however, regarding who or how many physicians practice emergency
      medicine. The purpose of this study is to determine the total number of
      physicians practicing clinical emergency medicine during a specified period, to
      describe certain characteristics of those individuals, and to estimate the total
      number of full-time equivalents (FTEs), as well as the total number of
      individuals needed to staff those FTEs. METHODS: Data were gathered from a survey
      of a random sample of 2,062 hospitals drawn from a population of 5,220 hospitals
      reported by the American Hospital Association as having, or potentially having,
      an emergency department. The survey instrument addressed items such as
      descriptive data on the institution, enumeration of physicians in the ED, as well
      as the total number working during the period June 1, 1997, through June 14,
      1997. Demographic data on the individuals were also collected. RESULTS: A total
      of 942 hospitals responded (a 45.7% return rate). These hospitals reported a
      total of 5,872 physicians were working during the specified period, or an average
      of 7.48 persons scheduled per institution. The physicians were scheduled for a
      total of 297,062 hours. The average standard for FTE was 40 clinical hours per
      week. This equates to 3,713 FTEs or 4.96 FTEs per institution. The ratio of
      persons to FTEs was 1.51:1. With regard to demographics, 83% of the physicians
      were men and 81% were white. Their average age was 42 years. As to professional
      credentials, 58% were emergency medicine-residency trained and 53% were board
      certified in emergency medicine; 46% were certified by the American Board of
      Emergency Medicine. CONCLUSION: Given that there are 4,945 hospitals with EDs and
      given that the data indicate there are 4.96 FTEs per ED, the total number of FTEs
      is projected to be 24,548 (standard error = 437). Given further that the data
      indicate a physician/FTE ratio of 1.51:1, we conclude that there are 36,990
      persons (standard error = 683) needed to staff those FTEs. When adjusted for
      persons working at more than one ED, that number is reduced to 32,026.

PMID- 9581145
TI  - Report of the Task Force on Residency Training Information, American Board of
      Emergency Medicine.
AB  - The American Board of Emergency Medicine gathers extensive background information
      on emergency medicine residents and the programs in which they train. Before the
      compilation of this report, this information has not been widely available.

PMID- 9581146
TI  - The workforce in emergency medicine.

PMID- 9581147
TI  - Baseball and beer: an analysis of alcohol consumption patterns among male
      spectators at major-league sporting events.
AB  - STUDY OBJECTIVE: Examination of alcohol consumption patterns of male spectators
      at two major-league baseball stadiums. METHODS: A prospective observational study
      was conducted at two stadiums over the course of three games at each venue. We
      approached 1,084 male spectators of drinking age in a consecutive fashion at two
      junctures: at the entrance gate and during the fifth inning inside the stadium's
      concourse. Of those approached, 747 (68.9%) participated. After verbal consent,
      participants completed a questionnaire and blew into a breath analyzer. The
      results were blinded and later analyzed. RESULTS: Forty-one percent of all
      participants tested positive for alcohol. The highest consumption occurred in the
      20- to 35-year-old age group. In this age group, 50.8% had consumed some alcohol,
      and 10.8% had a blood alcohol level of .08% (intoxicated) or higher. Almost 5% of
      all participants tested during the fifth inning collection were intoxicated and
      claimed to be driving. CONCLUSION: Of the spectators tested, those in the 20- to
      35-year-old age group were most likely to have consumed alcohol and to be legally
      intoxicated. A disturbing number of spectators who had blood alcohol levels of
      .08% or higher late in the game claimed to be driving home.

PMID- 9581148
TI  - Drugs of abuse and alcohol in weekend drivers involved in car crashes in Belgium.
AB  - STUDY OBJECTIVE: To determine levels of alcohol and drugs of abuse in weekend
      drivers injured in car crashes. METHODS: This study was the first systematic drug
      and alcohol testing of blood and urine samples of drivers injured in weekend car
      crashes in Belgium. Five collaborating hospital in Flanders participated. All
      injured weekend drivers admitted to the emergency units from July 1, 1994, to
      June 30, 1995, were included in the study sample. Sampling times were from Friday
      at 8 PM to Monday at 8 AM. RESULTS: Of the 211 injured drivers, 47.9% had
      positive test results for screenings for drugs or alcohol; 35.5% only for
      alcohol, 6.6% only for drugs, and 5.7% had positive results for both alcohol and
      drugs. Of the 87 weekend drivers with positive alcohol test results, 8% had a
      blood alcohol concentration (BAC) level below 80 mg/dL, 25.3% had a concentration
      between 150 and 190 mg/dL, and 39% had a BAC of 200 mg/dL or greater. There seems
      to be a consistent association between the consequences of the weekend crashes
      and the use of alcohol, drugs, or both. More than 50% of those who had negative
      results for drugs and alcohol could leave the hospital within 24 hours after
      their car crash. For the majority of those with positive findings for alcohol
      only or for drugs and alcohol (respectively, 72% and 78%), hospitalization in a
      general hospital unit or ICU was necessary. CONCLUSION: The results suggest that
      testing drivers for use of alcohol alone is insufficient.

PMID- 9581149
TI  - Alcohol-related research and advocacy: much to do, many places to do it!

PMID- 9581150
TI  - Vertebrobasilar distribution stroke mimicking transtentorial herniation.
AB  - Strokes in the vertebrobasilar arterial distribution may result in a variety of
      physical findings and can be challenging to diagnose. We report a case of a 60
      year-old woman with infarction of the left midbrain, right pons, and bilateral
      thalami with physical findings resembling transtentorial herniation.

PMID- 9581151
TI  - Glottic positioning of the endotracheal tube tip: a diagnostic dilemma.
AB  - Distal placement of the endotracheal tube tip in the glottic opening is rarely
      discussed in most emergency medicine, surgery, and prehospital medicine texts. We
      report three cases of glottic intubation recognized after the patients were
      thought to have been successfully intubated. Glottic positioning of the
      endotracheal tube tip went unrecognized initially because of the absence of air
      heard over the epigastrium, the presence of bilateral breath sounds, and
      acceptable readings by both pulse oximetry and capnography. Recognition of this
      complication is aided by the use of radiographic findings, inappropriate
      endotracheal tube depth, and the presence of inadequate ventilatory volumes.
      Potential complications of glottic intubation include dislodgement of the
      endotracheal tube, kinking of the tube, and inadequate protection of the airway.

PMID- 9581152
TI  - Update: isolation of avian influenza A(H5N1) viruses from human beings--Hong
      Kong, 1997-1998.

PMID- 9581153
TI  - Reappraisal of mouth-to-mouth ventilation.

PMID- 9581154
TI  - Layperson CPR.

PMID- 9581155
TI  - Cecal hernia: a rare cause of intestinal obstruction.

PMID- 9581156
TI  - Pulse oximetry gap in carbon monoxide poisoning.

PMID- 9581157
TI  - Clinical policy for procedural sedation and analgesia in the emergency
      department. American College of Emergency Physicians.

PMID- 9581159
TI  - [Unwanted drug effects in clinical practice].
AB  - BACKGROUND AND OBJECTIVE: Unwanted drug reactions (UDR) in routine clinical
      practice remain largely unrecorded, even though such documentation can
      significantly contribute to quality assurance in drug therapy. This prospective
      study was undertaken to ascertain within a defined time period the frequency and
      significance of UDR in the medical wards of a general hospital (focus on
      gastroenterology) and find the organisational structures needed for its
      documentation. PATIENTS AND METHODS: All observed UDRs among a total of 4032 in
      patients were recorded on a simple registration form, filled in by doctors
      assigned to collect the information, which was then analysed in cooperation with
      the Drug Commission of the German Medical Council (AKdA). RESULTS: UDRs were
      recorded in 315 patients (7.8%), 135 of them (43%) already present on admission.
      101 patients had been admitted because of the UDR. Gastrointestinal disorders,
      particularly peptic ulcer, and skin rash were the most common UDRs. Individual
      drugs most frequently responsible were acetylsalicylic acid, cyclophosphamide and
      digoxin, the most common drug groups were nonsteroid analgesics, antibiotics and
      cytostatic drugs. The method employed proved to be practicable and cost
      effective. CONCLUSIONS: A simple and cost-effective system, integrated into the
      daily medical routine, can heighten awareness of UDRs among doctors and thus
      improve drug safety in hospitals, while concomitantly providing an important
      feature of further medical education.

PMID- 9581158
TI  - [Diagnostic and therapeutic procedures by doctors for patients in a hypertensive
      crisis. An inquiry in 56 internal medicine clinics].
AB  - BACKGROUND AND OBJECTIVE: Despite official guidelines on the diagnosis and
      treatment of hypertensive crisis, the extent to which they are being followed in
      routine medical practice is unknown. This study was undertaken to discover how
      hospital doctors were handling cases of hypertensive crisis (HC). MATERIALS AND
      METHODS: Physicians were requested to participate in a multiple-choice
      questionnaire study, relating to the diagnosis of HC, any emergency diagnosis and
      choice of antihypertensive drugs, these questionnaires to be distributed among
      the medical staff. Ultimately 463 questionnaires (one per doctor) were sent out
      and 325 were completed (response rate of 70%). RESULTS: The most frequently
      mentioned blood pressure values characteristics for HC were > 200 systolic and >
      120 diastolic. 160/90 was given most often as the therapeutic goal, which most
      doctors wanted to reach in an HC within 30 to 60 min. The calcium-antagonist
      nifedipine was the drug of first choice for almost all clinical presentations.
      Second was intravenously urapidil, an alpha-agonist. Nitroglycerin was named as
      first choice only for pulmonary oedema or myocardial infarction. In everyone of
      the stated conditions most doctors were eager to avoid using beta-blockers. As
      for the drug of first choice in associated myocardial infarction, 111 doctors
      named nifedipine, 28 wanted to avoid it and 45 considered it contraindicated.
      CONCLUSION: These data show a marked discrepancy between recommended guidelines
      and actual practice in the management of hypertensive crisis.

PMID- 9581160
TI  - [Diagnosis of a "hereditary pancreatitis" by the detection of a mutation in the
      cationic trypsinogen gene].
AB  - HISTORY AND CLINICAL FINDINGS: A 71-year-old woman was admitted with the
      suspected diagnosis of pancreatic carcinoma. As a child she had had repeated
      attacks of abdominal pain of undetermined cause. When aged 48 years she had
      developed diabetes mellitus. Her now 42-year-old daughter had from the age of 9
      years suffered from repeated attacks of acute pancreatitis that had finally led
      to chronic pancreatitis. The patient's 15-year-old grandchild was having
      recurrent bouts of abdominal pain. INVESTIGATIONS: Imaging procedures revealed
      calcifications in the pancreas and an infiltrating space-occupying lesion, about
      3 cm in diameter, in the head of the pancreas with lymph node and liver
      metastases. Cytological analysis of material aspirated from the space-occupying
      mass showed typical findings of ductal pancreatic carcinoma. FURTHER TESTS,
      TREATMENT AND COURSE: At first the patient's course was not typical for a
      genetically-determined disease, but the family history raised the suspicion of
      hereditary pancreatitis. A genetic test (Afl-III-RFLP test) demonstrated the
      mutation Arg 117 His in the cationic trypsinogen gene in all diseased or
      symptomatic family members. The patient died of the complications of the
      pancreatic cancer. CONCLUSION: Genetic tests are valuable in the diagnosis of
      hereditary pancreatitis, because the increased cancer risk can be met by frequent
      examinations in affected family members.

PMID- 9581161
TI  - [Terazosin].

PMID- 9581162
TI  - [State-of-the-art diagnosis of dyspepsia].

PMID- 9581164
TI  - [Halved fracture risk through 10% bone increase--an illusion in the therapy of
      osteoporosis?].

PMID- 9581163
TI  - [Hereditary liver diseases. Recent molecular genetic aspects].

PMID- 9581166
TI  - [Lymphocytic colitis during ticlopidine therapy].

PMID- 9581165
TI  - [Epithelial iron accumulation in gastric mucosal biopsies from myelodysplastic
      syndrome].

PMID- 9581167
TI  - [Cardiac troponin T in the diagnosis and follow up of suspected myocarditis].
AB  - BACKGROUND AND OBJECTIVE: Results of routine laboratory tests for demonstrating
      myocardial damage in patients suspected of having myocarditis are often negative.
      This study was undertaken to ascertain (1) whether measuring Tropinin T (cTnT) in
      these patients can sensitively determine myocardial cell death, (2) to what
      extent this correlates with the findings of endomyocardial biopsy, and (3)
      whether measurement of cTnT can provide noninvasive assessment of the course of
      myocarditis. PATIENTS AND METHODS: 80 consecutive patients (52 men, 28 women)
      with clinically suspected myocarditis were investigated. The main clinical
      symptoms were heart failure (n = 45), angina pectoris (n = 25) or cardiac
      arrhythmias (n = 10). In most patients the symptoms had developed in temporal
      relation to a viral infection. Coronary heart disease was excluded in all by
      coronary angiography. Interventricular septal endomyocardial biopsies were
      examined histologically and immunohistologically. cTnT was measured with a highly
      sensitive sandwich-immunoassay. RESULTS: An increased level of cTnT (> 0.1 ng/ml)
      was demonstrated in 28 of the 80 patients (35%). Myocarditis was diagnosed
      histologically in only 5 patients, but immunohistologically in 26 of 28 (93%)
      with a raised cTnT level and in 23 of 52 (44%) with a normal cTnT level. The cTnT
      level was more frequently elevated in patients with a brief rather than a long
      history of myocarditis. After 6 months the cTnT level was elevated in only 4 of
      28 patients with myocarditis, but the myocardial biopsy showed persisting
      myocarditis in 14 patients. CONCLUSION: Measurement of cTnT is a very sensitive
      way of demonstrating myocardial cell damage in patients clinically suspected of
      having myocarditis. Immunohistological analysis can often provide positive
      results even if the histological findings are unremarkable. The sensitivity in
      diagnosing of cTnT is greatest when the patient is tested shortly after the onset
      of symptoms.

PMID- 9581168
TI  - [Treatment of coronary pseudoaneurysm by stent-graft implantation].
AB  - HISTORY AND CLINICAL FINDINGS: A 54-year-old man was urgently admitted because of
      sudden onset of progressively worsening angina pectoris, his first attack.
      Physical examination was unremarkable. INVESTIGATIONS: Electrocardiography and
      laboratory tests excluded acute myocardial infarction. With the exception of
      hypercholesterolemia (total cholesterol 247 mg/dl) laboratory tests were normal.
      Coronary angiography revealed a 60% eccentric narrowing in the proximal part of
      the interventricular branch with adjacent aneurysmatic dilatation. Intravascular
      ultrasound (IVUS) showed a coronary pseudoaneurysm, its cavity communicating with
      the empty atheroma hole of an adjacent ruptured coronary plaque. TREATMENT AND
      COURSE: A 19 mm stent graft was implanted, via a percutaneously inserted balloon
      catheter system, in the region of the stenosis and the pseudoaneurysm. Subsequent
      angiography demonstrated a smooth nonstenotic lumen. The membrane of the graft
      (made of polytetrafluoroethylene [PTFE]), fixed between two thin metal stents,
      had occluded the pseudoaneurysm. Occlusion of an immediately distal septal branch
      briefly produced an asymptomatic rise of creatine kinase to maximally 173 U/l.
      Oral medication included ticlopidine hydrochloride (2 x 250 mg daily for 4
      weeks). The patient was symptom-free after the procedure and was discharged 5
      days later. CONCLUSION: Implantation of a new type of stent-graft provides quick
      and uncomplicated treatment of a coronary aneurysm. The membrane fixed between
      two stents prevents wash out of any thrombi. The method may also be applicable to
      other potentially thrombus-containing lesions.

PMID- 9581169
TI  - [Lambl's excrescence as tumorous heart valve mass].
AB  - HISTORY AND CLINICAL FINDINGS: A 44 year old woman consulted a general physician
      because of weakness and fatigue. 5 months ago otitis media and a urinary tract
      infection had been treated successfully with antibiotics. The physical
      examination was unremarkable except for healed scars after an orthopedic
      operation about 35 years ago and a resection of a benign tumor of the left breast
      about 14 years ago. INVESTIGATIONS: Except for a slightly elevated
      antistreptolysin titer the laboratory tests were normal. The ECG showed sinus
      rhythm, left axis deviation and normal ST-segments. In the transthoracic
      echocardiogram an echogenic mass adherent on the ventricular side of the
      noncoronary cusp of the aortic valve in size of 2 x 1.5 cm could be demonstrated.
      The mass moved with the normally functioning valve and prolapsed into the aorta
      ascendens. The Doppler-echocardiogram was normal. TREATMENT AND COURSE: Because
      of the size of this echogenic mass with unknown origin and the risk of an embolic
      event its removal was indicated. This was done without destroying the aortic
      valve. Postoperative echocardiography demonstrated normal valve function. The
      histologic examination showed an endothelialized mass, rich in fibers and with
      only a few fibroblasts and histiocytes, without smooth muscle cells, according to
      a Lambl's excrescence. CONCLUSION: Cardiac valve tumors are rare. The
      differentiation between surface excrescences on the cardiac valve and neoplasia
      is only possible by histologic examination. Because of its possible malignancy
      and the potential risk of emboli surgical treatment is indicated.

PMID- 9581171
TI  - [Palliative medicine in the Netherlands].

PMID- 9581170
TI  - [Therapy of adrenal cortex diseases].

PMID- 9581172
TI  - [Retaining of revenue from the coworker pool in repayment by the hospital
      representative. Decision of the Labor Court, Giessen, August 26, 1997].

PMID- 9581173
TI  - [Anticoagulation after venous thrombosis caused by type-II HIT syndrome].

PMID- 9581174
TI  - [Artificial administration of fluids to the dying].

PMID- 9581175
TI  - [The artificial pacemaker erythema].

PMID- 9581177
TI  - [Radiotherapy of follicle center lymphoma. Results of a German multicenter and
      prospective study. Members of the Study Group "NHL-early stages"].
AB  - PURPOSE: Follicle centre lymphoma grade I, II (REAL) or centroblastic-centrocytic
      lymphoma (Kiel classification) present a well defined clinical entity from a
      clinical point of view. These lymphomas are not curable by chemotherapy in early
      or advanced stages. They are treated by radiation therapy in early stages, but up
      to now the curative potency of radiotherapy has not been confirmed by prospective
      clinical trials. PATIENTS AND METHODS: Between January 1986 and August 1993 117
      adults with follicle centre lymphoma were recruited from 24 institutions to enter
      the multicentric prospective, not randomised clinical trial. Patients with
      histologically proven nodal follicle centre lymphoma of stages I, II and limited
      III were included. They were treated by a standardised radiotherapy regimen, in
      stage I by extended field and in stages II and III by total nodal irradiation.
      Dose per fraction was 1.8 to 2.0 Gy, in the abdominal bath 1.5 Gy up to a total
      dose of 26 Gy in adjuvant situation and 36 Gy to enlarged lymphoma. RESULTS: All
      patients developed a complete remission at the end of radiotherapy. Median follow
      up is 68 months. Overall survival of all patients in 86 +/- 3% at 5 and 8 years.
      Stage adjusted survival at 5 and 8 years was 89% for stage I, 86% for stage II
      and 81% for III. Patients in stages I and II < 60 years had survival rates of 94%
      at 5 and 8 years, patients > 60 years 63% (p < 0.0001). Recurrence free survival
      of all patients is 70% at 5 and 60 +/- 5% at 8 years. The number of recurrences
      is high with 29% at 5 and 41% at 8 years. All recurrences were seen within 7
      years. The probability of localised nodal in-field recurrences is 11% and 22% at
      5 and 8 years, respectively. Adverse prognostic factors were identified by
      multivariate analysis: age > 60 years, treatment breaks > or = 7 days and dose
      deviations > 20% from prescribed doses. Acute side effects of extended field
      irradiation were moderate. CONCLUSIONS: On the basis of these results
      radiotherapy is a potentially curative therapeutic approach in stages I, II and
      limited III of follicle centre lymphoma. The optimal technique is total lymphoid
      irradiation with doses of 30 Gy in the adjuvant situation and 40 to 44 Gy in
      enlarged lymphomas. The number of local recurrences leads to the assumption, that
      the extension of radiotherapy to the total lymphoid system might reduce their
      frequency.

PMID- 9581176
TI  - [Testicular intraepithelial neoplasms (TIN). An indication for radiotherapy?].
AB  - BACKGROUND: Testicular intraepithelial neoplasia (TIN), synonymous for carcinoma
      in situ of the testis, is a rarely observed preinvasive neoplasia located within
      the germinative epithelium. According to the current knowledge of the biology of
      TIN, it is the common precursor of all testicular germ cell neoplasms except
      spermatocytic seminoma. MATERIAL AND METHODS: This report provides a review of
      histopathology, epidemiology and diagnostic procedures for TIN and discusses the
      therapeutic options with particular respect to radiooncological aspects. RESULTS:
      TIN has a 70% rate of progression to invasive cancer within 7 years. Depending on
      the individual therapeutic setting surgery, chemotherapy and radiotherapy are
      alternative treatment modalities. In case of TIN in a single testis or bilateral
      TIN, local radiotherapy is the standard procedure. With 20 Gy recommended as
      standard dose in Germany, radiotherapy yields safe eradication of TIN. However,
      some of the patients show significantly reduced synthesis of testicular
      androgens. With respect to sporadic reports in the literature, total doses well
      below 20 Gy might be equally efficient to treat TIN safely. Yet, up to date
      neither the minimum dose for efficient treatment nor the toxicity profile after
      consecutive chemo-radiotherapy has been established. CONCLUSIONS: The currently
      recommended standard dose of 20 Gy in Germany is probably in excess of the
      minimum dose needed for safe eradication of TIN. Thus, new radiooncological
      strategies should aim at reducing the total dose of treatment in order to
      minimize late side effects while maintaining the high efficacy of radiotherapy.
      This topic is under investigation in a multicenter clinical trial.

PMID- 9581178
TI  - [Value of radiosurgery in first-line therapy of glioblastoma multiforme. The
      Heidelberg experience and review of the literature].
AB  - AIM: To describe the clinical results and the feasibility of a phase II dose
      escalation study of small boost target volumes with a radiosurgical technique in
      patients with positive early postoperative MRI scans. PATIENTS AND METHOD: Since
      1986, 35 patients were treated within a concept for first line therapy. Including
      criteria were residual tumor < or = 5 cm and Karnofsky performance score > or =
      70. The mean age was 54.5 years. The treatment concept included an operation for
      reduction of tumor volume and a postoperative irradiation. The postoperative
      irradiation was divided in 2 parts: first, a hyperfractionated (1.8 Gy single
      dose twice a day, 54 Gy total dose) irradiation was performed containing the
      tumor and the edema with a 2 cm safety margin. Secondly, a radiosurgical boost
      dose was delivered. The target volume of this radiosurgery was the contrast
      enhancing residual tumor in early postoperative MRI scans. The median boost dose
      was 15 Gy. Survival curves were calculated according to the Kaplan-Meier method.
      Quality of life was evaluated using objective criteria such as neurological
      findings, frequency of seizures and steroid medication. RESULTS: The median
      survival calculated from the time of diagnosis was 10.1 months. The 1- and 2-year
      survival rate were 35% and 6%, respectively. Young age tended to longer survival,
      patients younger than 53 years had a median survival of 10.4 months whereas
      patients older than 53 years showed a median survival of 9.2 months. The mean
      value of the boost volume was 22 cm3. Patients with smaller volumes had a median
      survival of 10.1 months and patients with bigger volumes showed a median survival
      of 9.9 months, 4.5 months after therapy, 75% of the patients showed improved or
      stable quality of life. CONCLUSION: The feasibility of a radiosurgically
      delivered boost dose after postoperative irradiation could be demonstrated. The
      observed survival rate is comparable to the survival rates reported in the
      literature. Whether or not the radiosurgery after postoperative irradiation is
      able to prolong survival can only be evaluated in a randomized phase III trial.

PMID- 9581180
TI  - [Improved reproducibility and comfort by standardized postural support in the
      irradiation of the female breast].
AB  - BACKGROUND: Positioning and immobilisation techniques are essential for precise
      radiotherapy. The currently available standardised positioning devices are
      insufficient. For this reason, we designed a new and generally usable hard foam
      positioning support cushion for the breast irradiation and tested its usefulness
      in a prospective study. PATIENTS AND METHODS: Fifty-five female breast cancer
      patients receiving adjuvant radiotherapy following breast conservative surgery
      were irradiated either without immobilisation (n = 27) or with the developed
      positioning support cushion (n = 28). The time necessary for patient set-up, the
      subjective lying comfort and--comparing portal images with simulator images--the
      reproducibility of the set-up were determined. RESULTS: It was possible to
      improve irradiation reproducibility significantly (average deviation without
      positioning support cushion: 8.4 mm, with positioning support cushion: 6.1 mm, p
      < 0.001). The additional time required for the positioning of the patient was in
      average 19 s (with positioning support cushion: 74 s, without cushion: 55 s). A
      significantly higher proportion of patients (72%) found the position with the
      hard foam cushion was pleasant, whereas only 46% of patients were pleased with
      the position without cushion. CONCLUSION: The positioning support cushion
      designed in our department seems to play an important role in quality assurance
      of external beam irradiation of the breast and significantly increases the
      patients' comfort in a supine position. Compared to conventional positioning and
      fixation devices it may be quickly and easily applied at low cost. Therefore, its
      use can be recommended.

PMID- 9581181
TI  - Changes in RBE of 14-MeV (d + T) neutrons for V79 cells irradiated in air and in
      a phantom: is RBE enhanced near the surface?
AB  - PURPOSE: The relative biological effectiveness (RBE) for inactivation of V79
      cells was determined as function of dose at the Heidelberg 14-MeV (d + T) neutron
      therapy facility after irradiation with single doses in air and at different
      depths in a therapy phantom. Furthermore, to assess the reproducibility of RBE
      determinations in different experiments we examined the relationship between the
      interexperimental variation in radiosensitivity towards neutrons with that
      towards low LET 60Co photons. METHODS: Clonogenic survival of V79 cells was
      determined using the colony formation assay. The cells were irradiated in
      suspension in small volumes (1.2 ml) free in air or at defined positions in the
      perspex phantom. Neutron doses were in the range, Dt = 0.5-4 Gy. 60Co photons
      were used as reference radiation. RESULTS: The radiosensitivity towards neutrons
      varied considerably less between individual experiments than that towards photons
      and also less than RBE. However, the mean sensitivity of different series was
      relatively constant. RBE increased with decreasing dose per fraction from RBE =
      2.3 at 4 Gy to RBE = 3.1 at 0.5 Gy. No significant difference in RBE could be
      detected between irradiation at 1.6 cm and 9.4 cm depth in the phantom. However,
      an approximately 20% higher RBE was found for irradiation free in air compared
      with inside the phantom. Combining the two effects, irradiation with 0.5 Gy free
      in air yielded an approximately 40% higher RBE than a dose of 2 Gy inside the
      phantom. CONCLUSION: The measured values of RBE as function of dose per fraction
      within the phantom is consistent with the energy of the neutron beam. The
      increased RBE free in air, however, is greater than expected from microdosimetric
      parameters of the beam and may be due to slow recoil protons produced by
      interaction of multiply scattered neutrons or to an increased contribution of
      alpha particles from C(n, alpha) reactions near the surface. An enhanced RBE in
      subcutaneous layers of skin combined with an increase in RBE at low doses per
      fraction outside the target volume could potentially have significant
      consequences for normal tissue reactions in radiotherapy patients treated with
      fast neutrons.

PMID- 9581179
TI  - [Prevention and therapy of acute radiation-related morbidity of the skin and
      mucosa. II, Recommendations of the literature].
AB  - BACKGROUND: In a German multicenter questionnaire, answered by 89 departments, we
      had examined the strategies to prevent or to treat the acute morbidity of the
      skin and mucosa associated to radiation therapy. In this work, the
      recommendations from the literature are compared to the results of the
      questionnaire. METHODS: An extensive research on common data information systems
      (Medline, Cancerlit, DIMDI and others) was performed. The criteria included the
      organ related morbidity and therapeutic strategies for its reduction. The
      obtained data were compared to the results from the questionnaire. RESULTS: The
      study data found by the research often demonstrate small patient numbers and
      little convincing results. However, as in the questionnaire, the joint principle
      seems to be the reduction of acute inflammatory tissue reaction by evasion of
      bacterial and mycotic overgrowth and reduction of exo- and endogenous toxins.
      CONCLUSIONS: Further studies with more convincing results are required.

PMID- 9581183
TI  - Radiotherapy of bone metastases of a spinal meningeal hemangiopericytoma.
AB  - Hemangiopericytoma is a rare tumor arising from pericapillary cells or pericytes
      of Zimmerman, and can occur anywhere capillaries are found. We describe a patient
      with a meningeal hemangiopericytoma who was treated with primary surgical
      resection and experienced multiple bone metastases 20 years after the first
      treatment. This patient with multiple bone metastases was treated with multiple
      courses of irradiation and good palliation was achieved.

PMID- 9581184
TI  - [Value of radiotherapy in disseminated highly malignant non-Hodgkin's lymphoma.
      Comment on the article by U. Kaiser, R. Pfab, K. Havemann, Strahlenther Onkol
      1997, 173, 136-40 (No. 3)].

PMID- 9581182
TI  - [Significance of apoptotic processes in radiotherapy. II].
AB  - Apoptosis is known as an active process of cell death forced by radio- and
      chemotherapy. Therefore, established concepts (terms, therapy schemes) will
      reflect a picture different from that usually seen, when examined under the
      apoptotic point of view. Furthermore, the development of new concepts for
      innovative diagnosis, prognosis and therapy could be accomplished. This is an
      attempt to reveal actual features of both aspects.

PMID- 9581185
TI  - [Which action mechanisms are secured in the treatment of radiogenic side effects
      by hyperbaric oxygenation? Comment on the article by A. Hartmann, M. Almeling, U.
      M. Carl, Hyperbaric oxygenation (HBO) in the treatment of radiogenic side
      effects, Strahlenther Onkol l996, 172, 641-8 (No. 12)].

PMID- 9581186
TI  - [Comment. Hyperbaric oxygenation (HBO) in the treatment of radiogenic side
      effects. Clinical experiences are decisive!].

PMID- 9581187
TI  - [Regional radiotherapy with chemotherapy (VMB) compared to subtotal-nodal
      irradiation. A Stanford study].

PMID- 9581188
TI  - [Malignant second tumors in patients after therapy of Hodgkin's disease at the
      Royal Marsden Hospital].

PMID- 9581189
TI  - [Acute and chronic radiation effects in patients with collagenoses].

PMID- 9581190
TI  - Visual suppression of vestibular nystagmus.
AB  - The realisation of combined movements of the head and eyes requires the capacity
      to modulate the vestibulo-ocular reflex (VOR) but the absence of sufficiently
      rapid visual feed back results in an open loop function. This reflex must be
      modulated by other mechanisms. Two options are discussed. A modulation of the
      gain of the reflex loop is not satisfactory for small combined movements of the
      head and eyes as it would no longer permit the effective compensation for
      unexpected perturbations of movement of the head. An additive mechanism modifying
      the VOR through the addition of an other ocular movement is limited by the
      constrictions of latency, speed and amplitude of such movement. According to
      experimental conditions, varying complementary effect of the two mechanisms seems
      to result in maximum efficiency. This paper attempts to include the mechanism of
      the ocular fixation index (OFI) among the models of study. The OFI applied to a
      pendular test is, by the nature of its stimulus, more physiologic and more
      capable of being integrated into existing models. In the usual conditions of the
      test, the additive model is probably dominant with a preponderant role in the
      ocular pursuit system. But whatever may be the part of each mechanism, the OFI is
      not only dependent on the integrity of the floccular inhibition of the VOR but on
      the numerous cortical and subcortical structures involved in the realisation of
      voluntary ocular movements. This information should encourage clinicians to
      investigate the ocular movements of patients presenting vertigo, particularly
      those with visual instability on head movements.

PMID- 9581191
TI  - Ocular fixation index and mathematical models.
AB  - Ocular fixation test and ocular fixation index (OFI) never have been interpreted
      in terms of mathematical models, despite their widespread diffusion. However,
      ocular fixation is a typical case of visual-vestibular interaction, and
      mathematical models have proven very helpful in interpreting some mechanisms of
      this interaction, e.g. those of the optokinetic-vestibular interaction. In the
      present paper, a first attempt is proposed toward a model interpretation of OFI.
      By using very simple mathematical models, the hypothesis is tested that visual
      suppression of vestibular nystagmus results from direct action of smooth pursuit
      system (SPS). The aim is to draw consequences and recognize possible limits of
      this hypothesis. Dependence of OFI on SPS performance is examined. Although the
      available experimental data are insufficient for comprehensive validation of the
      model, the results agree with the current interpretations. In particular,
      quantitative support is given to the sensitivity of OFI to central vestibular
      diseases. Although the interpretation of visual suppression and OFI in terms of
      mathematical models is still at a very preliminary stage, models may provide a
      theoretical reference framework for the interpretation of new experimental
      results and/or suggest new test protocols.

PMID- 9581192
TI  - Sensitive detection of noise-induced damage in human subjects using transiently
      evoked otoacoustic emissions.
AB  - Thirty-eight males (76 ears) exposed to occupational noise were investigated
      using transient-evoked otoacoustic emissions. Based upon the hearing loss at 4
      kHz, they were classified into four described groups. Ten normally hearing
      subjects (20 ears) without exposure to occupational noise were used as controls.
      Significant changes in response amplitude, reproducibility, and signal to noise
      ratio (SNR) in broadband and frequency-bands (1, 2, 3, 4 kHz) were revealed
      between control subjects and the patients of group I exposed to noise with normal
      pure-tone audiometric thresholds. The changes of response amplitudes,
      reproducibility (%), and SNR were not significant between the group I and the
      patients of group II with mild hearing loss (< or = 40 dB) at 4 kHz. When the
      patients suffered from hearing loss beyond 40 dB HL at 4 kHz, emission amplitude,
      reproducibility, and SNR showed significant changes, whereas the percentage of
      absent emissions also showed significant changes. From these data, we conclude
      that TEOAE testing is more sensitive than pure-tone audiometry in the detection
      of early noise-induced damage. The test could be proposed as a hearing screen for
      monitoring employees with early noise-induced hearing loss.

PMID- 9581193
TI  - Our classification of tympanic retraction pockets.
AB  - A classification of tympanic retraction pockets is indispensable in order to
      standardise their evaluation. In this manner, the evolution of the pathology can
      be carefully followed and the most appropriate therapy chosen. The authors
      propose adapting their classification to endoscopy which permits the inspection
      of the depths of certain pockets, otherwise invisible to examination under
      microscope, thus ensuring a better follow-up.

PMID- 9581194
TI  - An unusual localisation of Kaposi's sarcoma: the external auditory canal.
AB  - The epidemic form of Kaposi's sarcoma is associated with human immunodeficiency
      virus infection. Cutaneous and mucosal manifestations are frequently reported in
      the ENT sphere, mostly involving the oral cavity. The external and middle ear are
      only rarely concerned with only one case of a mastoid lesion without extension to
      the external auditory canal (EAC) being reported to this day. The present article
      describes the first case of involvement of the EAC with extension to adjacent
      structures. This patient presented other Kaposi lesions and had been treated by
      systemic hormonal therapy. Thereafter local injection of a cytotoxic agent was
      given without effect. Finally, radiotherapy resulted in a 50% regression of the
      tumour mass. The epidemiologic factors and therapeutic modalities with their
      results are described.

PMID- 9581195
TI  - Intraparotid facial nerve neurilemmoma: a case report.
AB  - A case report of intraparotid facial nerve neurilemmoma is presented. The survey
      of this pathology is reviewed.

PMID- 9581196
TI  - An unusual complication of panendoscopy of the upper aero-digestive tract:
      esophageal perforation. A report of 3 cases.
AB  - Three cases of iatrogenic esophageal perforation are presented from a series of
      1275 panendoscopies of the upper aero-digestive tract utilising rigid esophoscopy
      (0.24%). In all cases, the diagnosis was made during the endoscopy permitting
      immediate surgical treatment under the same anesthesia, via thoracoscopy or
      laparoscopy in two cases and by means of thoracotomy in the remaining case. The
      perforation was localised at the level of the inferior third of the esophagus in
      all three cases. In spite of the early intervention, there was one mortality in a
      patient whose pre-existing fibrothorax created a hazardous terrain.

PMID- 9581197
TI  - Papillary thyroid carcinoma arising in the wall of a thyroglossal duct cyst.
AB  - The thyroglossal duct cyst is the most common anomaly in thyroid development.
      However, carcinomas arising in a thyroglossal duct cyst are rare entities. To
      date, approximately 125 cases have been reported, the majority being papillary
      thyroid carcinomas. In most cases the diagnosis is established only after
      excision of a clinically benign thyroglossal duct cyst. The etiology of such
      tumors remains unclear but de novo origin is generally proposed. Controversies
      exist in relation to a rational and effective therapeutic approach. A further
      case of thyroglossal duct papillary carcinoma affecting a 55 year-old Spanish man
      is presented to highlight the clinicopathological features of this condition.
      Preoperative computed tomography performed on our patient showed irregular
      calcium deposits adjacent to the hyoid bone. Cytohistological and
      immunohistochemical studies showed a papillary thyroid carcinoma with abundant
      psammoma bodies. Surgery consisted only of a Sistrunk procedure. In view of the
      prolonged course of papillary carcinoma, long-term follow-up is mandatory.

PMID- 9581198
TI  - An unusual neck mass: the Warthin tumor.
AB  - The cystoadenolymphoma or Warthin's tumor is a benign lesion of the salivary
      glands and principally of the parotid gland. We report a case of a 62 year old
      white male seen at our Institute for evaluation of an asymptomatic right neck
      mass located 2 cm below the mandible at the anterior margin of the
      sternocleidomastoid muscle. The echography showed a lymphoid structure simulating
      a lymphoproliferative process. Histologic examination of the surgical specimen
      revealed a Warthin's tumor. We discuss the importance of considering Warthin's
      tumor in the differential diagnosis of an isolated neck mass, and report our
      experience over a ten year period in the surgical management of neck masses.
      Additionally, the literature concerning extraparotid Warthin's tumors is
      reviewed.

PMID- 9581199
TI  - Metastatic cervical adenopathy revealing a Grawitz tumour. A case report.
AB  - The author presents a case of metastatic cervical adenopathy whose primary was
      found in an advanced but still latent Grawitz tumour. This veritable metastatic
      disease and the problems it raises, are discussed.

PMID- 9581200
TI  - Invasive sino-nasal aspergillosis: a case report.
AB  - A case of invasive sino-nasal aspergillosis in an immunocompromised child is
      reported. Prognosis of this fulminant disease is usually poor. This paper reviews
      the early symptoms, clinical manifestations, risk factors, diagnosis and
      treatment. Awareness of the disease and early diagnosis by histological
      examination is essential. Treatment should consist of early administration of
      i.v. Amphotericin B and extensive surgical debridement.

PMID- 9581201
TI  - Nd:YAG laser-assisted uvulopalatoplasty for snoring.
AB  - Uvulopalatopharyngoplasty (UPPP) has been acknowledged as the surgical treatment
      of choice for snoring. More recently, laser-assisted uvulopalatoplasty (LAUP) has
      emerged as a reliable, safe, less invasive technique in the surgical treatment of
      snoring. Our experience includes 90 patients treated by means of Nd:YAG laser
      assisted uvulopalatoplasty and the results are presented. The value of different
      factors (age, sex, snoring loudness, pharynx appearance, Muller manoeuver,
      presence of apnoeic episodes, overweight) in predicting success or failure of
      laser surgery has been evaluated. Good results were obtained in 80% of our
      patients. We found excessive snoring loudness and apnoeic episodes to be
      statistically associated with failure of LAUP to correct snoring. The other
      mentioned factors cannot be used in predicting the outcome of Nd:YAG laser
      assisted uvulopalatoplasty.

PMID- 9581202
TI  - Nasal mucosal sarcoidosis: a case report.
AB  - The authors present a case of nasal mucosal sarcoidosis. Its low incidence may be
      due to unawareness of this sometimes forgotten entity. Crusting and nasal
      obstruction may be the first symptoms of this multisystemic disease. With the
      nasal endoscope, today's most helpful tool for examining the nose and its
      adjacent structures, the otolaryngologist can diagnose this disease at an early
      stage.

PMID- 9581203
TI  - Vocal cord immobilisation in diffuse idiopathic skeletal hyperostosis (DISH).
AB  - Advanced forms of diffuse idiopathic skeletal hyperostosis or Forestier's disease
      can induce dysphagia and significant respiratory symptoms such as hoarseness,
      dyspnea, snoring and laryngeal stridor. Severe respiratory distress is very rare.
      Two identical cases of chronic respiratory distress due to bilateral vocal cord
      adduction-fixation in conjunction with skeletal pathology in the cervical area
      are presented. The clinical, diagnostic and therapeutic work-up and the
      prognostic outcome of the laryngeal pathology are discussed.

PMID- 9581204
TI  - Aging. To sleep, perchance to dream.

PMID- 9581205
TI  - Treatment research in geriatric psychiatry. From regulatory to public health
      considerations.

PMID- 9581206
TI  - Delusions and hallucinations in an adult day care population. A longitudinal
      study.
AB  - The frequency of the manifestation of delusions and hallucinations (d/h) among
      participants of adult day care centers was examined, as was the relationship of
      d/h to demographic and medical variables, agitation, depressed affect, and
      dementia. Changes in d/h were also assessed over a 1-year period, and those
      changes were compared with changes in agitation, depressed affect, and dementia.
      Depressed affect and agitation were related both to delusions and to
      hallucinations. Dementia was also related to d/h, although a substantial
      percentage of individuals who were not diagnosed with dementia also experienced
      some type of d/h. Finally, delusions were more prevalent and generally tended to
      relate more strongly to agitation, depressed affect, and dementia than did
      hallucinations.

PMID- 9581207
TI  - Age differences in behaviors leading to completed suicide.
AB  - The authors described retrospectively the premorbid self destructive behaviors of
      suicide victims to determine whether these behaviors differ with age. One hundred
      forty one suicide victims, age 21-92 years, were studied by psychological
      autopsy. Older age was significantly associated with more determined and planful
      self-destructive acts, less violent methods, and fewer warnings of suicidal
      intent. Age differences in the behaviors leading to suicide indicate that
      intervention in the midst of a suicidal crisis may be less effective in elderly
      persons than in younger people. Primary prevention should be the focus of efforts
      to decrease suicide rates in late life.

PMID- 9581208
TI  - A structured trial of risperidone for the treatment of agitation in dementia.
AB  - Fifteen patients with dementia and agitated behavior were treated in a 9-week
      structured trial of risperidone. Agitation remitted in all patients, and
      aggressive behaviors improved early in the course of treatment. The modal optimal
      risperidone dose was 0.5 mg/day. Extrapyramidal symptoms developed at some point
      during the trial in eight patients, and cognitive skills declined in three
      patients. These results indicate that risperidone is effective for treatment of
      agitation in elderly patients with dementia, although adverse extrapyramidal or
      cognitive effects may occur, even with low doses.

PMID- 9581209
TI  - The relationship between patient, informant, social worker, and consensus
      diagnoses of personality disorder in elderly depressed inpatients.
AB  - Two psychiatrists simultaneously administered the Personality Assessment Form
      (PAF) to 20 depressed geropsychiatric inpatients and to 20 of their relatives
      (informants). A social worker also completed PAF ratings, and a consensus
      conference independently assigned an Axis II diagnosis. For patient interviews,
      categorical and dimensional interrater reliability indices for cluster and total
      personality disorders (PDs) were generally marginal. For informant interviews,
      categorical interrater reliability indices for cluster and total PDs were also
      marginal, but dimensional reliability was high. Consistent with previous
      research, agreement between categorical scores yielded by the four assessment
      methods was poor, but agreement between dimensional scores was generally better.
      It appears that patients, family members, and staff maintain different
      perspectives on patients' personality that, if overlapping, may provide useful
      diagnostic data.

PMID- 9581210
TI  - Short-term administration of selegiline for mild-to-moderate dementia of the
      Alzheimer's type.
AB  - As a follow-up to an earlier study showing short-term benefit in inpatients with
      more severe dementia, the authors studied the short-term cognitive, functional,
      and behavioral effects of selegiline in outpatients with mild-to-moderate
      dementia of the Alzheimer type (DAT) by means of a double-blind, randomized,
      crossover study of placebo vs. selegiline. Fifty outpatients with mild-to
      moderate DAT and no behavioral disturbances were given selegiline in two 8-week
      treatment periods separated by a 4-week washout. Outcome was assessed with
      standardized measures of dementia severity, daily functioning, behavior, and
      cognition. There was no drug-placebo difference in any outcome measure.
      Selegiline did not show short-term benefit in this study, contrary to the earlier
      study, perhaps because the patients were studied less intensively and/or lacked
      behavioral problems that could show response, although the medication was well
      tolerated.

PMID- 9581211
TI  - Higher cerebrospinal fluid MHPG in subjects with dementia of the Alzheimer type.
      Relationship with cognitive dysfunction.
AB  - The authors sought to determine the relationships between cerebrospinal fluid
      (CSF) levels of three neurotransmitter monoamine metabolites and cognitive
      function. CSF was collected from subjects with dementia of the Alzheimer's type
      ([DAT] n = 28) and control subjects (n = 10) for determination of CSF 5
      hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxy-phenylglycol (MHPG), and
      homovanillic acid (HVA) levels. All subjects underwent systematic assessment to
      determine cognitive function. Subjects with DAT had higher concentrations of CSF
      MHPG. In the overall sample, cognitive function was inversely correlated with CSF
      levels of MHPG but not with 5-HIAA or HVA. Within the DAT sample, these
      correlations did not achieve significance.

PMID- 9581212
TI  - Depression among African American nursing home patients with dementia.
AB  - The authors compared 218 black and 68 white nursing home patients with dementia
      for differences in the prevalence, recognition, and treatment of depression.
      There were no racial differences in depressive symptoms, but whites were
      significantly more likely to receive a diagnosis of "possible depression" and
      there were few racial differences in clinical, social, or demographic factors
      associated with depression. Depression was often unrecognized and undertreated in
      both racial groups; several depression instruments developed for use in dementia
      had good reliability and validity among blacks; and there were no significant
      differences in depressive symptoms or diagnosis between U.S.-born and Caribbean
      born black patients. The absence of any appreciable interracial or intraracial
      differences in depression symptoms or diagnoses may reflect uniformity in nursing
      home selection criteria or lessening of mood differences that may have existed
      before admission.

PMID- 9581213
TI  - Identifying persons with dementia by use of a caregiver telephone interview.
AB  - A telephone screening assessment designed to identify persons likely to have
      dementia was conducted in a random community sample of 4,403 adults. Because of
      the cognitive impairment of the subjects, information was obtained from
      caregivers. Twenty-nine subjects were identified as likely to have dementia. Of
      these, 15 agreed to a complete dementia assessment conducted in their residence,
      and all were diagnosed with dementia. There was high reliability between the
      caregiver telephone interview and the clinical examination.

PMID- 9581214
TI  - Electroconvulsive therapy for epilepsy and major depression.
AB  - In this first report of electroconvulsive therapy (ECT) for the simultaneous
      treatment of seizures and depressive episodes, the authors discuss the use of ECT
      in the treatment of complex-partial seizures and major depression in a geriatric
      patients who refused antidepressant and antiepileptic medication. ECT has
      numerous anticonvulsant effects, including elevated seizure threshold and
      decreased seizure duration, which make it a useful adjunctive therapy in epilepsy
      that is refractory or not amenable to treatment with medication.

PMID- 9581215
TI  - Retrospective review of the effects of sertraline on 32 outpatients with
      dementia.

PMID- 9581216
TI  - Epidemiology of dementia and Alzheimer's disease.
AB  - The prevalence of dementia in subjects 65 years and older in North America is
      approximately 6%-10%, with Alzheimer's disease (AD) accounting for two-thirds of
      these cases. If milder cases are included, the prevalence rates double. Both
      causative and associative genes for AD have now been identified. The search for
      nongenetic risk factors has been less conclusive. Only age and family history of
      dementia are consistently associated with AD in all studies, but putative,
      protective agents such as estrogen, nonsteroidal anti-inflammatory agents
      (NSAIDs), and vitamin E are now undergoing clinical trials.

PMID- 9581217
TI  - Dementia in older minority populations. Issues of prevalence, diagnosis, and
      treatment.
AB  - Dementia continues to be a major disease that affects older Americans. It has
      been estimated that up to 25% of all community-dwelling elderly individuals in
      the United States suffer from signs or symptoms of dementia. Little, however, has
      been written on dementia as it relates to older minority populations. The purpose
      of this article is to discuss the prevalence of dementia in elderly minority
      populations, describe some of the unique issues related to the diagnosis and
      treatment of dementia in these populations, and make recommendations aimed toward
      improving the quality of life for elderly minority individuals with dementia.

PMID- 9581219
TI  - Management of Alzheimer's disease in a primary care setting.
AB  - This article covers a broad topic from the pragmatic point of view of a primary
      care physician. The perspective is that of a primary care physician who teaches
      resident physicians and students in a medical school and for almost 20 years has
      conducted clinical research in patient care settings, including a large Health
      Maintenance Organization in Seattle, Washington. This article addresses four
      general areas that are important for the management of dementia in primary care
      settings: recognition and diagnosis, treatment in the community (treatment before
      a person becomes permanently or semipermanently institutionalized), treatment as
      the disease progresses, and minimization of excess disability.

PMID- 9581218
TI  - Differential diagnosis and early detection of dementia.
AB  - Of the many potential causes of dementia, Alzheimer's disease (AD) is the most
      common and accounts for approximately two-thirds of cases in older populations.
      Typical clinical features help differentiate various other conditions. Screening
      laboratory tests are generally sufficient for routine evaluations; brain imaging
      assessments also assist in the differential diagnosis by identifying structural
      and functional abnormalities. Because new treatments for AD are more likely to
      delay disease onset than to reverse neuronal damage, early detection methods have
      practical treatment implications. Recent studies combine genetic risk with
      neuroimaging assessments as a method of early disease detection; additional
      techniques aimed at increasing sensitivity and specificity are under development.
      Such strategies should eventually assist in the early detection of AD and
      therapeutic monitoring of brain function during antidementia treatments.

PMID- 9581220
TI  - Psychosocial and behavioral interventions for Alzheimer's disease patients and
      their families.
AB  - In the absence of definitive treatments for Alzheimer's disease and related
      dementias, researchers in a variety of disciplines are developing psychosocial
      and behavioral intervention strategies to help patients and caregivers better
      manage and cope with the troublesome symptoms common in these conditions. These
      strategies include cognitive interventions, functional performance interventions,
      environmental interventions, integration of self interventions, and pleasure
      inducing interventions. Although more research is needed to further develop these
      strategies and establish their best use, psychosocial and behavioral
      interventions hold great promise for improving the quality of life and well-being
      of dementia patients and their family caregivers.

PMID- 9581221
TI  - Cholinergic deficiency in Alzheimer's disease. Pathogenic model.
AB  - Genetic vulnerability factors are becoming more important in AD, yet only a
      minority of cases are familial, and of these only a portion are genetically
      determined. Because, early in the course, neurodegeneration is occurring in
      vulnerable cholinergically innervated regions and not throughout the brain as a
      whole, AD may be conceptualized as a corticolimbic system neurodegenerative
      disorder involving the entorhinal cortex, hippocampus, and amygdala. This
      conceptualization has obvious implications for the development of therapies since
      future interventions may be designed to prevent or slow neurodegeneration or
      improve clinical signs by modulating risk factors, beta-amyloid deposition, and
      phosphorylation of tau proteins; inhibiting inflammatory or oxidative processes;
      or enhancing cholinergic function in various ways. The recently reported effects
      of antioxidants, including vitamin E and selegiline, in prolonging time to
      institutionalization, death, or significant worsening, is one example of the
      feasibility of this approach, as are the observations that anti-inflammatory use
      may reduce AD risk and that long-term cholinesterase inhibitor use may delay
      nursing home placement. At present, approaches that are focused on
      neurotransmitter systems may prove more immediately accessible targets for
      therapeutic intervention.

PMID- 9581222
TI  - Alzheimer's disease. Cholinergic therapy and beyond.
AB  - While much of the Alzheimer's disease (AD) research community turns its spotlight
      on genetics, molecular biology, and the neurotoxicity of beta-amyloid, there is a
      more subtle but equally significant shift in focus emerging within AD therapeutic
      circles. Once devoid of specific treatment options, the field now enjoys a choice
      of two Food and Drug Administration (FDA)-approved cholinesterase inhibitors and
      the prospect of several more in the near future. In addition, therapy for AD is
      rapidly expanding beyond the central cholinergic hypothesis to include
      neuroprotective agents and the possibility of interfering with basic mechanisms
      involved in the pathogenesis of this disorder. Clinically, we have entered the
      era of viable cholinergic therapies, and we are already moving beyond that
      starting point to an era of effective combination approaches. This article
      provides a clinical framework for these current and potential new therapies.

PMID- 9581224
TI  - Advance directives, competency evaluation, and surrogate management in elderly
      patients.
AB  - As patients age, their capacities for memory, judgment, reasoning, planning, and
      decision-making may erode. Preparing for the time when these losses occur
      involves three important strategies: advance directives, competency evaluation,
      and surrogate management. Advance directives allow currently competent patients
      to record the kind of medical procedures they desire if they become incompetent
      in the future. Competency evaluations determine the mental competence of a
      patient and require special training for the physician. The need for surrogate
      management increases as a patient's cognitive deficits worsen and often requires
      involvement of the legal system. This paper addresses these important strategies
      in detail.

PMID- 9581223
TI  - The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer's disease.
AB  - A variety of neuropsychiatric symptoms occur in Alzheimer's disease (AD)
      including agitation, psychosis, depression, apathy, disinhibition, anxiety,
      purposeless behavior, and disorders of sleep and appetite. Neuropsychiatric
      symptoms have been related to cholinergic deficiency and improve after treatment
      with cholinomimetic agents. Cholinergic drugs are unique among psychotropic
      agents in exerting disease-specific and broad-spectrum effects. These
      observations provide the basis for the cholinergic hypothesis of the
      neuropsychiatric symptoms of AD, suggesting that the cholinergic deficit of AD
      contributes to the neuropsychiatric symptoms of AD and that cholinomimetic
      therapy ameliorates the behavioral disturbances accompanying AD.

PMID- 9581225
TI  - Mental health services for Alzheimer's disease. Current trends in reimbursement
      and public policy, and the future under managed care.
AB  - Behavioral or psychiatric symptoms in Alzheimer's disease are strongly related to
      the use of health care services and result in a significant emotional and
      financial burden for families. This paper is an overview of major trends in the
      organization and funding of mental health services for people with Alzheimer's
      disease, emphasizing specific public policy and reimbursement initiatives that
      have affected acute and long-term care. Recent trends reflecting increased
      federal scrutiny of Medicare-reimbursed services and the current and future
      challenges in providing mental health services to people with Alzheimer's disease
      within managed care and capitated health plans are also addressed.

PMID- 9581226
TI  - [The economy and anesthesia].

PMID- 9581227
TI  - [Economic aspects of anesthesia. I. Health care reform in the German Republic].
AB  - Implications for Hospitals and Departments of Anaesthesiology. This article
      outlines the new German health care laws and their impact on the statutory health
      care system, hospitals and anaesthesia departments. The German health care system
      provides coverage for all citizens, although financial support from the public
      sector is on the downgrade. Hence, pressure to reduce public sector health care
      spending is likely to continue in the near future. Hospital costs account for one
      third of total health care spending in Germany, and hospitals are facing
      increasing economic constraints: the volume and the charges for specific medical
      treatments are negotiated between the hospitals and the insurance agencies (or
      sickness funds) in advance. Only part of hospital care is still reimbursed on the
      basis of a per diem rate, and an increasing number of services are based on fixed
      payments per case or treatment. Reducing the costs for this treatment is
      therefore of utmost importance for hospitals and hospital departments. The
      prospective payment system and the pressure to contain costs demand a controlling
      system that allows for cost accounting per case. However, an economic evaluation
      must include comparative analysis of alternative therapeutic options in terms of
      both costs and outcome. Economic aspects challenge the traditional relationship
      between physicians and patients: doctors are still the advocates of their
      patients, but also act as agents for their institutions. Nevertheless, not only
      economic issues, but also ethical priorities and the value of an anaesthetic
      practice must be considered in the era of cost containment. Anaesthetists must be
      actively involved in providing high-quality care with its obvious benefits for
      the patient and be able to resist efforts to cut out expensive treatment
      modalities regardless of their benefits.

PMID- 9581228
TI  - [The importance of bronchial hyperreactivity in anesthesiology].
AB  - Airways of patients with bronchial hyperreactivity (BHR) are characterised by
      exaggerated bronchoconstriction in response to a variety of stimuli; bronchospasm
      may be elicited during induction and maintenance of anaesthesia. The prevalence
      of BHR in normal populations is approximately 10%. BHR is an important feature of
      clinical asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis,
      atopy, upper respiratory tract infections and smoking. This review will outline
      some important aspects of the pathophysiological basis of BHR, i.e., neural and
      inflammatory mechanisms. Furthermore, it should assist in identifying patients at
      risk and update perioperative anaesthetic considerations. Prophylaxis of airway
      reflex activation and an appropriate anaesthetic plan should prevent airway
      constriction. Since tracheal intubation is the major risk factor to induce
      bronchospasm intubation should be avoided whenever possible and regional
      anaesthesia preferred. If tracheal intubation is unavoidable, propofol and
      ketamine can be recommended as induction agents. Prophylaxis of intraoperative
      bronchospasm and initial therapy, such as deepening of anaesthesia, inhalational
      administration of sympathomimetics and anticholinergics, and i.v. use of local
      anaesthetics and corticosteroids are outlined. Despite its popularity
      theophylline offers little benefit during anaesthesia. Adequate preoperative
      evaluation and preparation of the patient with BHR will contribute to optimising
      anaesthetic management of patients with BHR.

PMID- 9581229
TI  - [Pioneer in orotracheal intubation: Eugen Tschudy. The first emergency intubation
      for airway obstruction?].

PMID- 9581230
TI  - [The effect of endothelin on granulocyte-endothelium interaction].
AB  - PURPOSE: The interaction of activated granulocytes and endothelial cells
      influences not only capillary permeability but also increases pulmonary vascular
      resistance. The aim of this study was to evaluate the role of endothelin-1 (ET-1)
      during the granulocyte-mediated increase in pulmonary pressure. METHODS: The
      experiments were performed on isolated and ventilated rabbit lungs perfused with
      a blood-free buffer solution. Isolated, washed human granulocytes were injected
      into the pulmonary artery and stimulated by 10(-6) M N-formyl-L-leucin-methionyl
      L-phenylalanine (FMLP). Pulmonary arterial pressure (PAP) was continuously
      registered, and perfusate samples were taken to determine ET-1 and eicosanoid
      levels. To analyse the role of ET-1, six lung preparations were pretreated with
      the ETA receptor antagonist BQ123 (10(-6) M) prior to FMLP injection. To analyse
      the role of thromboxane A2, six additional lung preparations were pretreated with
      the cyclooxygenase inhibitor diclofenac (10 micrograms/ml). Additionally,
      granulocytes were stimulated in vitro with FMLP for 15 min, and ET-1
      concentration was measured in the supernatant. RESULTS: Immediately after FMLP
      injection, PAP increased to 18.5 +/- 1.6 mmHg, descending to values 4.8 +/- 0.8
      mmHg above the baseline after 15 min. At this time, ET-1 could be detected in the
      perfusate. The concentrations of the cyclooxygenase products thromboxane A2 and
      prostacyclin remained nearly unchanged during the observation period.
      Pretreatment with the ETA receptor antagonist BQ123 significantly reduced the
      pressure response after FMLP injection (p < 0.01 at 5 and 10 min; p < 0.05 at 15
      and 30 min). Pretreatment with the cycloocygenase inhibitor diclofenac failed to
      inhibit the pressure reaction evoked by activated granulocytes. In contrast to
      this, ET-1 was not detected after in vitro stimulation of granulocytes.
      CONCLUSION: ET-1 is involved as a mediator of pulmonary vasoconstriction due to
      granulocyte activation. Since in vitro FMLP-stimulation of human granulocytes did
      not induce ET-1 production, it seems likely that isolated activated granulocytes
      would not produce ET-1, but provoke the endothelial cells to release ET-1 in the
      pulmonary circulation.

PMID- 9581231
TI  - [The effect of total intravenous anesthesia with propofol, alfentanil and
      vecuronium (TIVA) on bronchial mucosal transport].
AB  - PURPOSE: The mucociliary escalator of the lung is an important protective
      transport system by means of which inhaled particles and microorganisms are
      removed from the tracheobronchial system. In the present prospective study the
      effect of total intravenous anaesthesia with propofol, alfentanil, vecuronium,
      and oxygen-air ventilation on bronchial mucus transport velocity (BTV) was
      investigated. METHOD: 10 patients undergoing major abdominal surgery were
      included in the study. In all patients anaesthesia was induced and maintained
      with propofol, alfentanil, and vecuronium. Ventilation was assisted with a
      mixture of air and oxygen (FiO2:0.35). The BTV was measured preoperatively in the
      conscious patients one day before surgery while they received local anaesthesia
      with 10 ml of 1 percent lidocaine and after the end of the operation during
      intubation anaesthesia. BTV was determined with a small volume of albumin
      microspheres labelled with technetium -99m, which was deposited on the dorsal
      surface at the lower ends of the right and left main bronches via a catheter
      placed in the inner channel of a fibre-optic bronchoscope [7]. The study was
      approved by the ethics committee of our hospital. RESULTS: The administered dose
      of propofol was 3.0 g (1.8-5.5), of alfentanil 26 mg (20-50), and of vecuronium
      20 mg (16-34) (median with range). The duration of mechanical ventilation up to
      the time of measurement was 5 h (3.0-9.5). TIVA produced a decrease of BTV in the
      right (9.7 vs 4.9 mm/min) and left main bronchus (11.3 mm/min vs 5.3 mm/min).
      CONCLUSIONS: Total intravenous anaesthesia with propofol, alfentanil, and
      vecuronium depressed mucociliary flow in patients with healthy lungs. The period
      for recovery of mucociliary clearance and the possible disadvantage in patients
      with increased pulmonary risk (e.g. patients with chronic bronchitis and
      abdominal surgery) should be clarified in further studies.

PMID- 9581232
TI  - [The basics of transfusion. 1. General transfusion methods and treatment with
      erythrocyte concentrates].

PMID- 9581233
TI  - [Problems with infusion of vasoactive drugs].
AB  - An infusion system that is insufficiently equipped with an alarm device in case
      the syringe pumps are obstructed, may gravely endanger patient safety. In a
      patient with septic shock, an obstruction of the infusion system led to periodic
      application of norepinephrine boli. Sudden haemodynamic disturbances in
      critically ill patients should be evaluated for pathological causes as well as
      for technical failure in the infusion system. A sensitive alarming system of
      syringe pumps may help to eliminate inappropriate drug delivery. For safe
      infusion of vasoactive drugs the following conditions are highly recommended: a
      singular syringe pump, a high volume delivery at a low drug concentration, a
      pressure-controlled infusion device and a short and pressure-resistant infusion
      system.

PMID- 9581234
TI  - High-dose chemotherapy and hematopoietic stem cell transplantation for relapsed
      or refractory diffuse large-cell non-Hodgkin's lymphoma.
AB  - The use of high-dose chemotherapy and transplantation for chemotherapy sensitive
      relapsed diffuse large-cell non-Hodgkin's lymphoma is now the gold standard for
      patients who are candidates for such therapy. Recent data also demonstrates the
      relative effectiveness of this approach for patients who are induction failures
      but are continuing to respond to conventional therapy at the time of
      transplantation. Newer approaches such as the use of novel agents to modify the
      transplant regimen, newer cytokines, or alternative sources of hematopoietic stem
      cells need to be tested in order to improve the outcome in patients with
      chemotherapy resistant disease.

PMID- 9581235
TI  - High-dose therapy followed by stem cell transplantation in partial response after
      first-line induction therapy for aggressive non-Hodgkin's lymphoma.
AB  - Patients with aggressive non-Hodgkin's lymphoma who fail to achieve a complete
      remission (CR) with standard induction therapy have a poor prognosis with
      conventional-dose salvage therapy alone. Retrospective series have suggested that
      early introduction of high-dose salvage therapy with autologous stem cell
      transplantation (ASCT) may benefit partial-responder (PR) patients. However, two
      randomized studies (of 69 and 51 patients with partial clinical responses) failed
      to demonstrate any advantage of intensive therapy. By contrast, the GELA
      comparative study on 94 PR-patients (residual disease being histologically
      documented in 53 patients) suggested that high-dose therapy with ASCT improves
      survival. Interpretation of all these results is complicated by the heterogeneity
      of patient populations with respect to initial prognostic factors, induction
      regimens and, in particular, the criteria used to define partial response.
      Gallium CT scan and magnetic resonance imaging are now used to better explore
      residual masses. In the future, early restaging with these imaging techniques
      might be used to delineate patients who are likely to achieve CR from those who
      will fail to induction treatment and could be candidates for experimental
      treatments.

PMID- 9581236
TI  - High-dose therapy for diffuse large-cell lymphoma in first remission.
AB  - Diffuse large-cell lymphoma (DLCL) is curable by first-line conventional
      chemotherapy in 50%-60% of patients. High-dose therapy makes no contribution to
      this group of patients and, if applied indiscriminately as first-line
      consolidation therapy, is likely to unnecessarily increase overall morbidity and
      mortality. Instead, recent interest has been directed towards (a) the
      identification of a group of patients with a poor prognosis, and (b) the
      intensification of first-line treatment for such patients with high-dose therapy
      and allied regimens. Many prognostic factors have now been standardised, while
      studies are progressing in the identification of newer prognostic factors, such
      as the molecular markers. Multi-centre randomised trials are currently in
      progress to determine the appropriate level of treatment for prognostic subsets,
      with the value of high-dose therapy being assessed for those in the worst
      prognostic groups.

PMID- 9581237
TI  - Conditioning regimens before transplantation in patients with aggressive non
      Hodgkin's lymphoma.
AB  - Substantial progress has been made in understanding the role of
      autotransplantation in aggressive non-Hodgkin's lymphoma. At present, the
      clinical indications for high-dose therapy include patients with relapsed or poor
      prognosis disease. Hematopoietic reconstitution with peripheral stem cells has
      rendered transplantation less toxic but the optimal preparative regimen remains
      to be found. It should combine a high antitumor activity with acceptable toxicity
      to normal tissues. The literature, on combinations of drugs with or without total
      body irradiation, was reviewed with regard to this objective. BEAM, CBV and ICE,
      the most common chemotherapy regimens can be considered safe as they cause low
      transplant-related morbidity. The combination of fractionated TBI and etoposide
      or cyclophosphamide was not found to be superior. However, it must be kept in
      mind that comparisons were made on registry data or retrospectively. In every
      case, relapse of the residual primary disease argue for the need for more
      effective strategies such as tandem transplantation or sequential high-dose
      chemotherapy with stem-cell support. To obtain an objective evaluation, these new
      preparative regimens need to be tested in controlled trials with treatment groups
      stratified for known prognostic factors.

PMID- 9581238
TI  - Consensus conference on high-dose therapy with hematopoietic stem cell
      transplantation in diffuse large-cell lymphoma. Type of cells, optimal
      mobilization of stem cells--positive and negative selection.
AB  - Stem cell transplantation has played a role in the management of diffuse large
      cell lymphoma for decades. The optimal source of the stem cells and the proper
      composition of the cellular graft product has not been defined. The field is
      changing rapidly and the future is likely to hold improvements and requirements
      that will further benefit the patient!

PMID- 9581239
TI  - Immunotherapy in conjunction with autologous and allogeneic blood or marrow
      transplantation in lymphoma.
AB  - Relapse is the major obstacle for successful transplantations in lymphoma. One of
      the ways to reduce relapse rates is to intensify immune-mediated effector
      mechanisms. Graft-versus-lymphoma may be achieved either by administration of
      cytokines or by allogeneic cell-mediated adoptive immunotherapy. The use of
      allogeneic non-myeloablative stem cell transplantation (SCT) is another option
      which may be applicable to all age groups. It remains to be seen whether non
      myeloablative SCT will result in a lesser degree of relapse and higher disease
      free survival in lymphoma patients.

PMID- 9581240
TI  - Tumor vaccination strategies combined with autologous peripheral stem cell
      transplantation.
AB  - Despite advances in high-dose therapy with autologous stem cell transplantation
      for lymphomas, relapse of the underlying disease remains a significant obstacle.
      Recent advances in cancer vaccine development, specifically, the molecular
      identification of novel tumor antigens and understanding of cellular signals
      delivered by cytokines and costimulatory molecules required for efficient T-cell
      activation, now make it possible to consider combining active specific
      immunotherapy with PSCT as a strategy for elimination of minimal residual
      disease. As a model lymphoma-specific antigen, vaccination with patient-specific,
      immunoglobulin idiotype has been shown to be therapeutically effective when
      combined with marrow transplantation in small animal models. These preclinical
      studies predict the feasibility of immunization of human patients with B-cell
      malignancies vaccinated with this antigen in the post-transplant setting in
      ongoing clinical trials, especially for T-cell responses. In the future, other
      vaccine formulations, based on gene therapy approaches to enhance the
      immunogenicity of whole lymphoma cells or the identification of novel, defined
      antigens selectively expressed on lymphoma cells, as well as combined strategies
      of pre- and post-transplant tumor vaccination are envisioned.

PMID- 9581241
TI  - Unicompartmental knee arthroplasty for medial gonarthrosis: 5 to 9 years follow
      up evaluation of 77 knees.
AB  - A total of 77 knees in 60 consecutive patients were operated on for medial
      gonarthrosis using a cemented porous coated anatomical (PCA) unicompartmental
      knee arthroplasty. Their average age was 71.3 years; 11 were men and 49 women.
      Clinically, the results in 67 knees were rated as being good to excellent, with
      mean preoperative and postoperative flexion of 123 and 122 deg, respectively. No
      deep infections or deep venous thrombosis occurred, but there was one dislocation
      of the femoral component. Overall clinical and radiographic results were
      satisfactory in 88% at 7.0 years' follow-up. Kaplan-Meier survivorship analysis
      indicated that the failure rate of unicompartmental knee arthroplasty was 12% at
      average follow-up. In patients aged 70 years or more, unicompartmental knee
      arthroplasty for medial gonarthrosis should be considered an excellent
      alternative to high tibial osteotomy.

PMID- 9581243
TI  - Treatment of cutout of a lag screw of a dynamic hip screw in an intertrochanteric
      fracture.
AB  - Sixteen consecutive patients with cutout of a lag screw of a dynamic hip screw
      fixation in an intertrochanteric fracture were treated with reinsertion of a lag
      screw, bone cement supplementation in the neck-trochanter, and subtrochanteric
      valgus osteotomy. Postoperatively, patients were permitted to ambulate with
      protected weight-bearing. Fourteen patients were followed-up for at least 1 year
      (median 2 years; range 1-3 years), and all had a solid union. The union period
      took a median of 5 months, with a range of 3-7 months. Usually, union of an
      intertrochanteric fracture was faster than that of subtrochanteric osteotomy (P <
      0.01). There were no complications of wound infection, loss of reduction, cutout
      of a lag screw, or osteonecrosis of the femoral head. From clinical and
      theoretical considerations, we conclude that despite cutout of a lag screw of a
      dynamic hip screw fixation being difficult to treat, out technique still can
      provide an excellent outcome. Therefore, we strongly recommend its wide use.

PMID- 9581244
TI  - Tissue response to polyglycolide and polylactide pins in cancellous bone.
AB  - An absorbable self-reinforced polyglycolide (SR-PGA) pin, 2.0 mm in diameter and
      15 mm in length, was implanted in the trabecular bone areas of the distal femur
      of 51 rats and a biodegradable self-reinforced poly-L-lactide (SR-PLLA) pin of
      the same size was inserted into the distal femur of the other hind leg of the
      same rats. The intact femora of eight non-operated rats were used as controls.
      Tissue reaction to the implants was examined within standardized sample fields
      radiographically, histologically, histomorphometrically, microradiographically
      and using oxytetracycline fluorescence studies. The follow-up periods of the
      groups consisting of five operated rats and one intact control rat were 1, 3, 6,
      12, 24, 36, 48 and 52 weeks. Eleven extra rats were operated on to ensure five
      samples in each follow-up group for the final analyses. The first signs of
      degradation of the SR-PGA pin were seen at 3 weeks, and the pin was totally
      degraded by 36 weeks. No signs of degradation of the SR-PLLA pin were observed
      during the follow-up period. Active new bone formation was seen close to the
      implant profile at 1 week in both groups. At 12 weeks the mean fractional osteoid
      formation surface was statistically significantly (P < 0.01) higher in the SR-PGA
      implanted specimens than in the SR-PLLA-implanted specimens. At that time there
      were also statistically significantly (P < 0.05) more phagocyting macrophages in
      the SR-PGA-implanted specimens than in the SR-PLLA-implanted specimens, which is
      in accordance with the degradation behaviour of both implants. The
      biocompatibility of polyglycolide and polylactide proved to be good.

PMID- 9581242
TI  - Surgical options for distal radial fractures: indications and limitations.
AB  - Distal radial fractures are common problems for the orthopedic surgeon, and
      various surgical treatments have been reported. However, each method has its
      indications, pitfalls, and limitations. It is important to select the appropriate
      procedure for the fracture pattern. We studied 115 consecutive patients including
      45 patients with distal radial fractures treated with percutaneous pinning, 67
      patients treated with external fixation, and 32 patients treated with assisted
      wrist arthroscopy. Percutaneous pinning was useful in extra-articular fractures
      and minimally comminuted intra-articular fractures, but was inadequate for
      patients with severe osteopenia and markedly comminuted intra-articular
      fractures. External fixation was indicated when intra-articular comminution was
      present. However, the dorsomedial fragment was often not reduced and maintained
      by this technique; additional pinning was needed to reduce this fragment. A
      dynamic-type fixator was feasible for younger patients who required early
      functional recovery. Arthroscopy provided accurate visualization of the wrist
      joint and the intra-articular fracture.

PMID- 9581245
TI  - Evaluation of imaging in loosening of hip arthroplasty in 326 consecutive cases.
AB  - Between 1989 and 1995, 326 hip arthroplasties were surgically revised in our
      clinic because of loosening. For evaluation of loosening, we used history,
      clinical examination, radiographs, bone scans and arthrography with digital
      subtraction technique. In 130 cases (40%), surgery was planned by plain
      radiographs. In 116 cases (89%) a correct diagnosis of loosened components was
      made. Of the 72 patients (22%) with an additional bone scan, 87% (63 patients)
      had a correct diagnosis. Fifty-four patients (17%) with different findings were
      examined by hip arthrography; in 83% (45 patients) the diagnosis was confirmed
      intraoperatively. In 93% (65 patients) of 70 patients (21%) with bone scans and
      arthrography, surgery confirmed the diagnosis. Sensitivity for loosening of the
      socket was 61% by bone scan and 85% by digital subtraction arthrography;
      specificity was 75% in each case. Sensitivity for loosening of the stem was 71%
      by bone scan and 65% by digital subtraction arthrography; specificity was 80% and
      88%, respectively. Our results showed that in most cases of suspected loosening
      of total hip arthroplasties, analysis of plain radiograph series can lead to an
      accurate diagnosis in 85%-90%. In cases of uncertainty, we suggest the additional
      use of digital subtraction arthrography, which has a similarly high diagnostic
      quality. Because of the low sensitivity of nuclide bone scanning (about 60%) and
      its dependence on prosthetic material and fixation, we do not recommend primary
      scintigraphy. It can be helpful in problematic cases with additional questions
      like activity of ectopic bone formation.

PMID- 9581246
TI  - Cell survival following bone-anterior cruciate ligament-bone allograft
      transplantation: DNA fingerprints, segregation, and collagen morphological
      analysis of multiple markers in the canine model.
AB  - Bone-anterior cruciate ligament-bone allograft transplantation has become
      recognized as a potential solution to reconstruction of the anterior cruciate
      ligament (ACL). The purpose of this study was to determine the time-dependent
      fibrocyte donor cell survival rate after cryopreserved bone-ACL-bone allograft
      transplantation. Additionally, bony incorporation of the pediculated bone plugs
      was examined. The ability to successfully transplant allogenous ACL fibrocytes
      and have them survive has not previously been documented. In this study, DNA
      fingerprints identified and documented the survival rate of the cellular DNA in
      transplanted ACL allografts for ACL re-construction in the knee joints of 10
      skeletally mature dogs. At 4, 8, 26 and 52 weeks after ACL allograft
      transplantation, DNA probes, H & E, Giemsa, Goldner, PAS and polarized light
      staining was done to demonstrate the time-dependent changes in the allografts
      after transplantation. At 4 weeks host fibrocytes began to grow into the graft;
      however, histologically the cells could not be distinguished as to host or donor
      origin. After 4 weeks the DNA pattern reflected only the band pattern of the
      host. This reveals the early cellular infiltration activity of the host into the
      ACL allograft, also demonstrated in the light microscopy stainings. The survival
      rate of transplanted allogenous ACL fibrocytes had not been documented before
      this study. There is no evidence that ACL allograft cells survive in the intra
      articular environment of the host's knee. Within 4 weeks ACL allografts became
      completely repopulated with host cells. The cells that migrate early into the ACL
      allografts are probably of synovial origin because they are present before
      revascularization and collagen reorganization occur. We conclude from this study
      that viable cells in transplanted ACL allografts did not survive longer than 4
      weeks after intra-articular transplantation. Advances in molecular biology may
      offer new approaches to alter or stimulate fibrocyte population and function in
      the transplanted ACL allograft used for ACL reconstruction. New methods to
      maintain the viability of donor cells may be necessary to improve the
      biomechanical and histological properties of autografts or allografts for ACL
      reconstruction.

PMID- 9581247
TI  - Effect of alignment of the transplanted graft extracellular matrix on cellular
      repopulation and newly synthesized collagen.
AB  - This study examines the effect of alignment of the transplanted graft
      extracellular matrix on cellular repopulation and new collagen synthesis. The
      lateral half of the patellar tendon was harvested as a tendon graft from Lewis
      rats and frozen at -80 degrees C. In order to maintain the original alignment of
      the graft extracellular matrix, the graft was transplanted to a same size defect
      in the patellar tendon of other Lewis rats (group I). For controls, the graft was
      transplanted in a lax condition after excision of only the distal half of the
      lateral side of a patellar tendon (group II). After transplantation, six animals
      in each group were killed at 3, 7, 14, and 28 days. Cellular repopulation was
      assessed by using fibrillar-actin (F-actin) labeling with rhodamine-phalloidin,
      and new collagen synthesis was detected by means of a polyclonal antibody against
      type III collagen aminopropeptide (pN collagen III). Collagen fibril profiles
      were observed under the transmission electron microscope. On the 3rd day after
      transplantation, no specific fluorescence was detected in either group. Specific
      labeling for F-actin and pN collagen III, however, was observed at both ends of
      the graft in both groups at 1 week and throughout the graft at 2 weeks after
      transplantation. Consistent with the actin bundles' orientation, pN collagen III
      was aligned parallel to the longitudinal axis of the graft in group I. Collagen
      fibrils with a smaller diameter, mixed evenly and everywhere with a larger
      diameter, increased gradually in group I. However, smaller collagen fibrils in
      group II increased more slowly and were distributed unevenly. In summary, the
      dense collagen arrangement in the native patellar tendon determined the alignment
      of the repopulating cells, and the distribution of newly synthesized collagen
      might be affected by the actin cytoskeleton within the repopulating cells.

PMID- 9581248
TI  - Long-term results of Salter and Chiari hip osteotomies in developmental hip
      dysplasia. A survey of over 10 years follow-up with a new hip evaluation score.
AB  - When conservative treatment of developmental hip dysplasia (DDH) does not render
      satisfactory results, surgical methods are indicated to gain a maximum of joint
      posture and stability. To assess the efficiency of these surgical procedures, the
      long-term results of the most often used pelvic osteotomies were examined. As
      common evaluation scores do not apply for DDH, we developed a specific score
      system of 100 points to integrate subjective factors such as patient's complaints
      with objective functional and radiological findings after surgical intervention.
      Our survey with an average postoperative follow-up examination of 10 years
      indicated that Salter's innominate osteotomy can render long-term pain relief and
      enable normal hip development, whereas Chiari's capsular arthroplasty does not.
      Here, subjective patient complaints do not correlate with clinical and
      radiological findings, which leads to unsatisfactory results. Ideally, patients
      aged 2-3 years can undergo Salter's innominate osteotomy whereas the Chiari
      osteotomy should be considered for patients older than 15 years. Even under
      optimal surgical conditions, Chiari's osteotomy cannot significantly prevent the
      development of joint arthritis. Undoubtedly, late results of both surgical
      procedures are dependent upon the initial stage of DDH. Additional upper femoral
      correction osteotomies have no further influence on hip development.

PMID- 9581249
TI  - Changes of sonographic, magnetic resonance tomographic, electromyographic, and
      histopathologic findings within a 2-month period of examinations after
      experimental muscle denervation.
AB  - This study compares sonographical, histopathological, magnetic resonance imaging
      (MRI), and electromyographical (EMG) findings following acute muscle denervation.
      We performed an experimental denervation of the supraspinatus and infraspinatus
      muscles on 35 New Zealand white rabbits by segment resection of the suprascapular
      nerve. The sonographical appearance of the supraspinatus muscle was followed and
      documented at short time intervals within a 2-month follow-up period. The
      sonographical, histopathological, and MRI changes due to denervation suggest a
      regular pattern. Apart from the reduction of the muscle diameter, there were
      considerable sonographical signs of denervation with an increase of echointensity
      and inhomogenicity of echotexture that appeared on day 14 after injury, and
      progressed continuously with time. MRI revealed a remarkable increase in signal
      intensity 3 weeks after denervation and reproducible T2 times. Pathological
      spontaneous activity on EMG could also be detected from day 14 after injury.
      Conventional histopathological staining methods (H&E, NADH, ATPase, basic and
      acid phosphatase) confirmed denervation and absence of reinnervation. The first
      nonspecific histopathological changes were seen 11 days after denervation in the
      form of moderately atrophic fibers. Typical histopathological signs of
      denervation appeared 3 weeks after nerve dissection. In summary, EMG, ultrasound,
      MRI, and histopathology each showed first abnormalities after about 2 weeks. In
      addition to EMG, sonography and MRI can document the course of muscle atrophy and
      mesenchymal abnormalities in neurogenic muscle lesions.

PMID- 9581250
TI  - The value of magnetic resonance imaging as postoperative control after
      arthroscopic treatment of osteochondritis dissecans.
AB  - The purpose of our study was to evaluate the value of MRI for preoperative
      arthroscopical planning in patients with osteochondritis dissecans. Based on the
      experience from 136 patients with osteochondritis dissecans of the knee or the
      ankle who were arthroscopically operated by retrograde drilling a follow-up study
      was carried out with 86 of them by clinical, radiological and postoperative
      magnetic resonance imaging (MRI) examinations. The evaluation was made by means
      of a visual analogue scale and a score system. The radiological findings were
      analysed according to the classification of Rodegerdts and Gleissner. The changes
      based on the MR images were classified according to our own pathoanatomical
      classification. The total score showed a significant improvement from 63.3 to
      79.6 points (knee) and from 50.6 to 70.4 points (ankle). In 72% of the cases, the
      findings of the MR images showed a defective cartilage surface in the area of the
      osteochondritis dissecans lesion. An increase of signal in the osteonecrotic area
      could be seen in 51% of the cases when using a short-time inversion recovery
      (STIR) image. Especially in patients with postoperative failures, a high
      percentage of cartilage defects (grade III) could be detected on the MR images
      (PS 500/10). Uptake of gadolinium-diethylene triamine tetra-acetic acid was
      regarded as a sign for revascularization. Radiographs did not correlate with
      these changes detected in the MR images. This retrospective study of an operated
      osteonecrosis dissecans by MRI provides more detailed information about eventual
      revascularization of the osteonecrotic area. With this information a more
      detailed preoperative planing for further cases should be possible.

PMID- 9581252
TI  - Good and relative indications for elbow arthroscopy. A retrospective study on 103
      patients.
AB  - The purpose of this study was to present our long-term experience with
      arthroscopic surgery of the elbow joint with special regard to diagnosis-specific
      results. Out of 121 patients undergoing elbow arthroscopy 103 were evaluated,
      with a mean follow-up of 6.2 years. The age of the patients at time of surgery
      ranged between 3 and 72 years. For documentation, the Figgie score was used. The
      results were related to the patients' pathology. The total score improved
      significantly from 49.3 to 89.1 (P < 0.05). There was no age dependency of the
      results, but there were correlations with the preoperative duration of symptoms
      and the individual job situation. Comparing the different parameters of the
      Figgie score, the aspect pain showed the greatest improvement. While patients
      with free joint bodies as well as septic or rheumatoid arthritis obtained a
      measurable benefit from the arthroscopic procedure, the postoperative improvement
      for the patients with severe degenerative arthritis was only limited. Patients
      with unspecific preoperative complaints showed no improvement at all. Thus, while
      patients with free joint bodies or synovitis without degenerative joint disease
      are good candidates for elbow arthroscopy, there is only a limited indication for
      patients with severe degenerative joint disease or patients with a restricted
      range of motion.

PMID- 9581251
TI  - Complications after treatment of patients with osteogenesis imperfecta with a
      Bailey-Dubow rod.
AB  - The purpose of this study was to analyse the complications using the Bailey-Dubow
      expanding intramedullary rods in patients with osteogenesis imperfecta. Between
      1985 and 1996 intramedullary rodding of 107 long bones with expanding Bailey
      Dubow rods was performed in 29 patients suffering from osteogenesis imperfecta.
      Indications for using rods included osseous deformities and bone deformities in
      combination with fractures. The average follow-up was 3.5 years (range 2 months
      to 9 years). The total complication rate in these patients was 63.5% (68 rods).
      The main complication was rod migration often combined with perforation of joint,
      bone and soft tissue. Additionally, there was a high incidence of new fractures
      as well as refractures. Other complications like infections, pseudarthrosis, lack
      of elongation or over-elongation of the rods, and loosening of the T-piece were
      only rarely seen. Based on our experience and the information available in the
      literature, the Bailey-Dubow rod is currently the most successful way to
      stabilize the growing long bones of patients suffering from osteogenesis
      imperfecta. However, when using this device, the surgeon as well as the parents
      of the patient must be aware of the high incidence of complications.

PMID- 9581253
TI  - Day-case simple extensor origin release for tennis elbow.
AB  - The results of day-case lateral release for resistant tennis elbow were evaluated
      in 20 patients after an average follow-up of 16 months. Using the outcome
      criteria of Verhaar et al. [4] an excellent result was obtained in 55%, a good
      result in 35% and a fair result in 10%, with all patients benefiting from
      surgery. We believe surgery should be offered at an earlier stage in the
      treatment of tennis elbow, with the simple and effective nature of the operation
      providing little justification for persisting with conservative treatment. With
      hindsight, three-quarters of our patients would have preferred earlier surgical
      referral.

PMID- 9581254
TI  - Level of physical activity in elderly patients after hemiarthroplasty for three-
      and four-part fractures of the proximal humerus.
AB  - We report on 13 physically active patients who performed sports activities at a
      weekend or recreational level when they suffered a severe proximal humerus
      fracture or fracture dislocation. All patients were treated using the NEER II
      hemiarthroplasty, 9 patients within 4 weeks after trauma and 4 patients 2, 5, 10
      and 15 months after trauma. At an average follow-up of 50 (range 6-98) months,
      all patients were evaluated, both by clinical review and radiographs. Patients
      obtained 69.0 points using the HSS score (Hospital for Special Surgery) for
      evaluation. Subjectively, 85% of the patients evaluated the result as 'good' or
      'excellent' on a visual analogue scale for satisfaction. There was no
      radiographic evidence of implant loosening. At an average period of 33 (range 16
      52) weeks 10 patients started with their physical activities again without a
      change in their participation level.

PMID- 9581255
TI  - Revision resurfacing knee arthroplasty for aseptic loosening.
AB  - This re-investigation presents our experience with revision resurfacing knee
      arthroplasty caused by aseptic failure. The evaluation of the results should
      elucidate the benefit of revision, its complications as well as the impact of the
      implant type used. The study involved 36 patients whose primary resurfacing knee
      prostheses failed by aseptic loosening. The rather elderly patients (average 68.3
      years) underwent revision 6 years later on average. In 30 cases (83.3%),
      arthroplasty could be repeated with resurfacing implants, whereas the use of
      hinge prostheses was unavoidable in 6 knees (16.7%). After an average of 7 years
      later, 30 knees were re-investigated according to the Hospital for Special
      Surgery (HSS) scoring system. Results were compared with the HSS values prior to
      revision. Complications and revised implant survivorship were reported
      chronologically. The revision knees had a 80% incidence of improved HSS score. In
      73.3% the outcome was graded as good or even excellent. In contrast, scoring
      values before revision were dissatisfying without exception. The early
      complication rate after operation was 25%. Persisting pain, instability and
      limited mobility led to repeated revision in two cases and arthrodesis of one of
      the knees. The outcome of revision after 7 years revealed a remarkable early
      complication rate. Nevertheless, good or excellent results could be scored after
      implantation of PFC, PFC-modular, TC and TCIII prostheses.

PMID- 9581256
TI  - A simple technique for correction of complicated tibial deformity including
      rotational deformity.
AB  - Although the simplest way to correct bone deformity is one-stage correction, the
      problem associated with that method is overstretching of the soft tissues, which
      limits the correction and leads to complications such as compartment syndrome or
      peripheral nerve palsy. If an adequate amount of tissue necessary for correction
      is formed in advance, the deformity can be corrected safely at one stage without
      overstretching of the tissues. A leg lengthening technique was employed to form
      the necessary tissues. After leg lengthening with an unilateral external fixator
      (Hifixator), deformities were corrected manually at one stage without anesthesia,
      and the corrected positions were again secured with the fixator. To correct
      rotational deformity, two sets of pins were inserted into the proximal bone
      fragment of the tibia at the time of the operation, and after lengthening the
      proximal pin clamp of the fixator was disconnected from one pin set and
      reconnected to the other set. We applied this method to four tibias of three
      patients without any complications. The tension of the tissues was monitored
      using a pressure sensor built into a Hifixator to prevent the tissues from
      overstretching. During and after the correction, the tension of the tissue was
      maintained at less than before the correction.

PMID- 9581257
TI  - Callus formation in the humerus compared with the femur and tibia during limb
      lengthening.
AB  - We investigated whether the callus formation in the humerus during the
      distraction period of limb lengthening proceeds at a higher rate than that in the
      femur and tibia. Ten achondroplastic patients underwent 3 bilateral humerus, 3
      bilateral femur and 4 bilateral tibia lengthenings. To reduce the confounding
      effect of bone size, we used bone mineral apparent density (BMAD) to compare the
      three groups; this is a volumetric bone mineral density measurement. BMAD in the
      distracted callus space was evaluated at 8 weeks after the start of distraction
      using dual-energy X-ray absorptiometry (mean +/- SD; g/cm3): in the humerus (0.24
      +/- 0.08) it was significantly higher than in the tibia (0.10 +/- 0.02), while
      there was no difference between the humerus and femur (0.35 +/- 0.11). We
      conclude that the callus formation in the humerus during the distraction period
      of limb lengthening proceeded at a significantly faster rate than in the tibia,
      but there was no significant difference between the humerus and femur.

PMID- 9581258
TI  - The effects of high-dose methotrexate on the development of cartilage lesions in
      a lapine model of osteoarthrosis.
AB  - To determine whether systemic administration of methotrexate (MTX) can prevent
      joint destruction in experimental osteoarthrosis (OA) in rabbits, the disorder
      was induced unilaterally in the knee joints of 40 rabbits by partial medial
      meniscectomy and sectioning of the medial collateral and both cruciate ligaments.
      A sham operation (arthrotomy only) was performed in another four animals. Effects
      on the cartilage of the femoral condyles were studied after 6 and 12 weeks.
      Twelve weeks after induction, femoral and tibial osteophyte formation was
      demonstrated on radiographs in all cases. Marked cartilage damage was found
      histologically (median Mankin score 10 vs 1 for non-operated controls; P < 0.05,
      Wilcoxon test). Cartilage proteoglycan (GAG) content (dye binding assay) was
      reduced in operated joints [63 +/- 8 (mean +/- SEM) vs 75 +/- 6 micrograms
      chondroitin sulfate/mg cartilage wet weight], and the leukocyte count in the
      joints was elevated (226 +/- 14 vs 7 +/- 3 leukocytes per microliter joint
      aspirate after injection of 0.5 ml saline solution; both P < 0.05, Wilcoxon
      test). The rate of GAG synthesis was unchanged (ex vivo labelling with 35S
      sulfate). Treatment with MTX (30 mg x kg body weight-1 x week-1 i.m., starting 12
      h postoperatively) reduced cartilage damage (median Mankin score 8 vs 10 for
      placebo, P < 0.05, Mann-Whitney U-test), but had no significant effect on the
      other parameters tested. No significant MTX effects were observed on cartilage
      from nonoperated joints. Our data indicate that MTX may have a limited
      therapeutic effect in experimental OA in the rabbit.

PMID- 9581259
TI  - Pelvic osteotomies: anatomic pitfalls at the pubic bone. A cadaver study.
AB  - Pelvic osteotomies for acetabular dysplasia include an osteotomy of the pubic
      bone. The anatomical consequences of two different approaches to the pubic bone
      were assessed by performing a triple osteotomy on a series of 12 fresh cadaver
      hemipelvises. The medial approach through a separate incision over the pubic
      symphysis was compared with the lateral approach through the incision used for
      the innominate osteotomy. Although the medial approach appears technically easy,
      there are several anatomical structures at risk, such as the femoral vein and the
      corona mortis. The lateral approach is safer, and it is easier to make the
      osteotomy close to the hip joint. The closer the osteotomy is to the hip joint,
      the smaller the chance of developing a non-union.

PMID- 9581260
TI  - Healing of tibial fractures is not impaired after acute hindlimb ischemia in
      rats.
AB  - The influence of transient circulatory arrest on the healing of closed tibial
      fractures was investigated in rats by the use of a hindlimb tourniquet technique.
      Twenty-four animals were randomly divided into three groups. In all animals, the
      left lower leg was fractured and fixed with an intramedullary nail system. In the
      ischemic group, complete acute transient ischemia for 4.5 h and neurapraxia of
      the sciatic and femoral nerves were induced prior to fracture. In the neurapraxia
      group, the sciatic and femoral nerves were crushed with forceps before fracture.
      In the control group, no other intervention than fracture was made. The rats of
      the control group ambulated normally 3-4 days after the operation. The animals of
      the ischemic and neurapraxia groups resumed normal weight-bearing after about 3
      weeks. After 6 weeks, all animals were killed, and mechanical strength and bone
      mineral turnover of the healing tibia as well as blood flow of the bone and
      musculature were evaluated. The weight of the tibia and the corresponding
      anterior tibial muscle in the ischemic and neurapraxia animals were reduced
      compared with the control rats. Bone mineral turnover was found to be lower in
      the ischemic group. There were no differences between the groups in mechanical
      strength nor in blood circulation of bone and muscle. In conclusion, complete,
      acute hindlimb ischemia for 4.5 h in rats did not cause delayed healing of closed
      tibial fractures.

PMID- 9581261
TI  - Rupture of the flexor pollicis longus tendon at the musculotendinous junction in
      a bowler.
AB  - Traumatic rupture of the flexor tendons at the musculotendinous junction is rare.
      A case of flexor pollicis longus tendon rupture at the musculotendinous junction
      is described. The mechanism of the tendon injury appears to be longitudinal
      traction on the contracted muscle during delivery of a bowling ball.

PMID- 9581262
TI  - The relevance of hydroxyapatite and spongious titanium coatings in fixation of
      cementless stems. An experimental comparative study in rat femur employing
      histological and microangiographic techniques.
AB  - Pure titanium rods plasma-spray coated with hydroxyapatite (HA) or porous
      titanium (Ti) of controlled roughness were implanted bilaterally in the distal
      femur of Sprague-Dawley rats to compare the extent of bone growth on the two
      types of coating. The relevance of other factors, like mechanical stability and
      biological adaptation of the bone to the insertion of a foreign body implant,
      were investigated in femora which were over-reamed (absence of primary fit) or
      reamed without insertion of the rod. Continuous tetracycline labeling for the
      first 30 days and for the last 2 weeks in the 90-day group was performed;
      histological/histometric, fluorescence and microangiographic studies were carried
      out on serial sections of the implanted and control femora. In the group of
      stable implants, HA-coated rods showed 90% integration versus 53% with Ti-coated
      implants (P < 0.001); in over-reamed implants neither surface bone growth nor
      endosteal fixation occurred, and both types of rods were surrounded by a thick
      layer of connective tissue. The study documented early adhesion of osteoblasts
      and direct deposition of bone matrix on the substrate, while on spongious
      titanium osteogenesis was observed only in proximity to the surface. Remodeling
      of the reactive, primary bone to mature, lamellar bone took the form of a capsule
      surrounding the implants and radial bridges connecting the latter to the
      endosteal surface. The number, height and thickness of these bridges appeared to
      be the factors determining implant stability, rather than the extent of the bony
      capsule on the perimeter of the implant. Integration was a function not only of
      mechanical conditions and surface geometry, but also of the biological response
      of the whole bone to changes in the vascularization pattern. The reported
      phenomena can be seen more easily in experimental models involving small rodents
      because of their fast bone turnover and revascularization, but it is expected
      that they take place, even at a lower speed, in clinical situations like
      cementless stems of total hip replacement.

PMID- 9581263
TI  - Simultaneous dorsal dislocation of the metacarpophalangeal and carpometacarpal
      joints of a finger.
AB  - A case of simultaneous dorsal dislocation of the metacarpophalangeal (MP) and
      carpometacarpal (CMC) joints in the little finger is presented. The patient
      required a second surgical intervention for volar subluxation of the MP joint
      which occurred while wearing a dorsal splint following open reduction of the MP
      joint and closed reduction of the CMC joint. Two years postoperatively, the
      patient was asymptomatic but was left with mild stiffness of the MP joint.

PMID- 9581264
TI  - The fate of missed atlanto-axial rotatory subluxation in children.
AB  - Torticollis in children can be due to atlanto-axial rotatory subluxation. If
      diagnosis, based on plain lateral radiography and on computed tomography, and
      specific treatment are delayed, reduction becomes difficult to accomplish.
      Atlanto-axial fusion might be indicated to cure the instability. Thus, a
      diagnostic delay may prevent restoration of cervical spine function. In acquired
      torticollis in children, radiographic evaluation is indicated if the symptoms are
      not relieved within 1 week, but immediate radiography is indicated in traumatic
      torticollis.

PMID- 9581265
TI  - Subcutaneous rupture of the tibialis anterior tendon: review of the literature
      and a case report.
AB  - Closed rupture of the anterior tibial tendon is uncommon, with 33 cases being
      reported previously. In this report we add another to these few. The literature
      is reviewed; late diagnosis is frequent, and the injury occurs in middle-aged and
      elderly patients after distorsion of the foot in plantar flexion and eversion.
      The treatment of the rupture in early and delayed cases is discussed.

PMID- 9581266
TI  - Bilateral spontaneous rupture of flexor digitorum profundus tendons.
AB  - Spontaneous tendon rupture is an unusual condition usually associated with
      underlying disease processes such as rheumatoid arthritis, chronic renal failure
      or bony abnormalities of the hand. We report a case of spontaneous, non
      concurrent bilateral rupture of flexor profundus tendons in an otherwise healthy
      individual. Treatment was successful and consisted of a two-stage reconstruction
      of the ruptured tendon.

PMID- 9581267
TI  - Anomalous palmaris longus muscle causing carpal tunnel-like syndrome.

PMID- 9581268
TI  - Management of a huge tumour of the humerus by total replacement of the humerus:
      an 11-year follow-up.
AB  - A massive tumour of the humerus was replaced using a total humerus replacement.
      The clinical and functional outcome at 11 years remains excellent.

PMID- 9581269
TI  - Fracture of the anterior superior process of the calcaneus: an often misdiagnosed
      fracture.
AB  - Fracture of the anterior superior process of the calcaneus has been considered an
      unusual injury. Following a sudden twist there is immediate pain on the outer
      aspect of the mid-portion of the foot and discomfort on weight-bearing. Three
      mechanisms of injury have been reported to cause the fracture. The diagnosis is
      often missed, and prolonged disability and local pain at the calcaneocuboid joint
      deserve further consideration. Oblique X-rays of the foot are helpful to
      visualize the fracture. Type III fractures may cause cartilage lesions and
      arthrosis; therefore, one should not wait long before excision or refixation of
      the fragment.

PMID- 9581272
TI  - One-pot synthesis of beta-D-Galf(1-->4)[beta-D-Galp(1-->6)]-D-GlcNAc, a 'core'
      trisaccharide linked O-glycosidically in glycoproteins of Trypanosoma cruzi.
AB  - Tin(IV) chloride-promoted condensation of benzyl 2-acetamido-3-O-benzoyl-2-deoxy
      alpha-D-glucopyranoside (4) with penta-O-benzoyl-beta-D-galactopyranose (6) gave
      the derivative of beta-D-Galp-(1-->6)-alpha-D-GlcNAc 7 in 80% yield. This was
      glycosylated with penta-O-benzoyl-alpha, beta-D-galactofuranose (5), employing
      the same catalyst, to afford the protected benzyl per-O-benzoyl-beta-D-Galf(1-
      >4)[beta-D-Galp(1-->6)]D-GlcNAc 10 in 41% yield. Alternatively, compound 10 was
      obtained directly in a one-pot reaction from 4, by sequential addition of 6 and 5
      (34% yield). beta-Glycosidic linkages were diastereoselectively formed. De-O
      benzoylation of 10, followed by heterogeneous catalytic transfer hydrogenolysis
      of the benzyl group afforded the free trisaccharide beta-D-Galf(1-->4)[beta-D
      Galp(1-->6)]-D-GlcNAc (14) in 98% yield from 10. Sodium borohydride reduction of
      14 gave the corresponding alditol, whose spectral data were identical to those
      reported for the alditol obtained from the 38-43 kDa cell-surface glycoprotein of
      Trypanosoma cruzi.

PMID- 9581270
TI  - Pseudoacids. I. 4- and 5-oxoacids.
AB  - Certain 4- and 5-oxoacids may exist in their cyclic lactol (or pseudoacid) forms.
      These commonly occur in compounds with proximate carboxylic acid and carbonyl
      (aldehyde or ketone) functions for the formation of five- or six-membered rings.
      Examples include trans-2,3-disubstituted aliphatic, (Z)-2,3-olefinic and o
      disubstituted aromatic acids. Crystal structures of compounds in these categories
      are reported: trans-4-methyl-3-oxo-6-hydroxytetrahydropyran-3-carboxylic acid
      (6), monoclinic, C2/c, a = 25.412 (5), b = 6.291 (1), c = 10.757 (2) A, beta =
      104.84 (3) degrees; penicillic acid (7), 4-methoxy-5-hydroxy-5-(2'
      propenyl)dihydrofuran-2-one, tetragonal, P4(2)/n, a = b = 15.83 (2), c = 7.016
      (11) A; mucochloric acid (8), (Z)-3,4-dichloro-5-hydroxydihydrofuran-2-one,
      triclinic, P1, a = 6.227 (5), b = 8.085 (5), c = 12.369 (9) A, alpha = 99.50 (5),
      beta = 102.38 (6), gamma = 90.29 (6) degrees; 2-methanoylbenzoic acid (9), 3
      hydroxy-1-(3H)-isobenzofuranone, monoclinic, P2(1), a = 4.006 (1), b = 11.489
      (2), c = 7.347 (1) A, beta = 97.50 (3) degrees; 2-ethanoylbenzoic acid (10), 3
      hydroxy-3-methyl-1-(3H)-isobenzofuranone, orthorhombic, P2(1)2(1)2(1), a = 5.199
      (6), b = 9.651 (14), c = 15.950 (17) A; 2-(2'-oxoethyl)benzoic acid (11), 3
      hydroxy-3,4-dihydroisobenzopyran-1-one, monoclinic, P2(1)/n, a = 4.651 (3), b =
      11.886 (7), c = 14.312 (11) A, beta = 90.86 (6) degrees. These compounds also
      exist in the cyclic forms in chloroform solution. A trimeric cyclic trioxane
      structure, analogous to paracetaldehyde, is confirmed as the solid form of 5
      oxopentanoic acid (1), triclinic, P1, a = 5.640 (4), b = 8.571 (8), c = 18.962
      (13) A, alpha = 78.68 (6), beta = 84.34 (5), gamma = 80.38 (6) degrees. In
      solution (NMR), mixtures of the open aldoacid, trimeric acid and cyclic
      pseudoacid exist. In both furanoid and pyranoid pseudoacids, endocyclic lactol C
      O bond lengths are lengthened (1.46-1.48 A), while the exocyclic C-O(H) bonds are
      shortened (1.38 A). Pseudoacids commonly form hydrogen-bonded chains linking the
      lactol hydroxy and carbonyl groups, but 3-hydroxy-3,4-dihydroisobenzopyran-1-one
      forms distinctive hydrogen-bonded dimers.

PMID- 9581273
TI  - A convenient synthesis of D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and L
      myo-inositol 1,4,5-trisphosphate (Ins(3,5,6)P3).
AB  - An efficient synthesis of an optically active inositol derivative that is a
      precursor to D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3, (-)) is described.
      Crystallization of the diastereomers of (+/-)-1-O-[(+)-menthoxycarbonyl]-6-O
      benzyl-2,3:4,5-di-O-isopropyl idene-myo- inositol diastereomers from methanol
      gives only one diastereomer. Alkaline hydrolysis gives the useful inositol
      derivative (-)-6-O-benzyl-2,3:4,5-di-O-isopropylidene-myo-inositol. Likewise,
      crystallization of the diastereomers of (+/-)-3-O-[(-)-menthoxycarbonyl]-4-O
      benzyl-1,2:5,6-di-O-isopropyl idene-myo- inositol from methanol gave a pure
      compound which could be hydrolyzed to give (+)-4-O-benzyl-1,2:5,6-di-O
      isopropylidene-myo-inositol, a precursor to D-myo-inositol 3,5,6-trisphosphate
      (Ins(3,5,6)P3,(+)). The ease with which these enantiomerically pure inositol
      derivatives were isolated may facilitate the synthesis of more complex inositol
      phosphate derivatives such as D-myo-inositol 1,3,4,5-tetrakisphosphate.

PMID- 9581276
TI  - Lipo-oligosaccharides of Campylobacter jejuni serotype O:10. Structures of core
      oligosaccharide regions from a bacterial isolate from a patient with the Miller
      Fisher syndrome and from the serotype reference strain.
AB  - Lipo-oligosaccharide (LOSa) was obtained by phenol-water extraction of bacterial
      cells of an isolate PG 836, identified as Campylobacter jejuni serotype O:10,
      from a patient who subsequently developed the Miller-Fisher syndrome (MFS). The
      product was separated into a water-insoluble gel of low Mr and a water-soluble
      component of high Mr. The structure of the core oligosaccharide region in LOSa is
      reported herein for comparison with LOSb from the C. jejuni O:10 reference
      strain, and is based on investigations carried out on: (1) O-deacylated LOSa; (2)
      the core oligosaccharide (OS 1a) liberated on acetic acid hydrolysis of the
      ketosidic linkages to lipid A, with accompanying loss of N-acetylneuraminic acid
      residues; (3) the product of the removal of phosphate residues from OS 1a to give
      OS 2a; and (4) the Smith degradation of OS 2a to yield a mixture of Os 3a and OS
      4a. The results revealed that the core oligosaccharide region in LOSa from the
      MFS bacterial isolate had chains (1a), of which some were terminated by an N
      acetylneuraminobiose [Neu5Ac(alpha 2-8)Neu5Ac] unit in a GD3 [Neu5Ac-Neu5Ac-Gal]
      epitope, and the inner regions of which were different from those of other C.
      jejuni serotypes. Similar experiments on LOSb from bacterial cells of the C.
      jejuni O:10 reference strain showed that the core oligosaccharide unit [1a, R = P
      (phosphoric monoester)] of LOSa from the MFS isolate was more uniformly complete
      than that of the O:10 reference strain [1b, R = AEP (2-aminoethylphosphate)]
      differing in the nature of the phosphate substituent at the inner heptose
      residue. The close structural relationship of LOSa from the MFS associated
      bacterium to LOSb from the O:10 reference strain runs parallel to that of the
      previously studied Guillain-Barre syndrome (GBS) associated bacterium typed as C.
      jejuni O:19 in comparison with the lipo-oligosaccharide from the reference
      strain. Preliminary studies on the high Mr components showed that those from the
      O:10 strains were indistinguishable from each other, but were structurally
      unrelated to those from the GBS associated C. jejuni serotype O:19 isolates and
      the O:19 reference strain [G.O. Aspinall, A.G. McDonald, and H. Pang,
      Biochemistry, 33 (1994) 250-255].

PMID- 9581277
TI  - Dimers of a GFG hexasaccharide occur in apple fruit xyloglucan.
AB  - Apple fruit xyloglucan is predominantly built up from XXXG, XXFG, and XLFG units
      (G = beta-D-Glcp-, X = alpha-D-Xylp-(1-->6)-beta-D-Glcp-, L = beta-D-Galp-(1-->2)
      alpha-D-Xylp-(1-->6)-beta-D-Glcp-, F = alpha-L-Fucp-(1-->2)-beta-D-Galp-(1-->2)
      alpha-D-Xyl p-(1-->6)-beta-D-Glcp-). However, small amounts of oligosaccharides
      with a less heavily branched glucan backbone also occur. Structural analysis of
      two such oligosaccharides, isolated from a xyloglucan preparation digested with
      endoglucanase i.v., using a combination of FAB mass spectrometry and 1H NMR
      spectroscopy, afforded the identification of GFG and a dimer of GFG. The finding
      of the dodecasaccharide GFGGFG as a structural element of apple fruit xyloglucan
      is most unusual.

PMID- 9581278
TI  - Structural studies on a sulfated polysaccharide from an Arthrobacter sp. by NMR
      spectroscopy and methylation analysis.
AB  - Structural characterization of a sulfated polysaccharide peptidoglycan complex
      (SP-PG) from an Arthrobacter sp. was performed by NMR spectroscopy and
      methylation analysis. In order to simplify the analyses, the desulfated SP-PG was
      used. NMR spectroscopy revealed the presence of a trisaccharide repeating unit
      and a disaccharide repeating unit. The trisaccharide unit was composed of two
      galactofuranosides and one glucopyranoside, and the disaccharide unit was of two
      galactopyranosides, as shown below. The methylation analysis showed that the
      polysaccharide consists mainly of a 4-linked galactopyranoside, a 6-linked
      galactopyranoside, a 6-linked galactofuranoside, a 2,6-linked galactofuranoside,
      a terminal galactopyranoside and a terminal glucopyranoside. These findings
      confirmed the structure indicated by the NMR spectroscopy. The repeating units
      determined in this study are novel.

PMID- 9581279
TI  - Isolation and structural characterisation of rhamnogalacturonan oligomers
      generated by controlled acid hydrolysis of sugar-beet pulp.
AB  - Controlled acid hydrolysis was applied to a deesterified beet pulp and the
      resulting soluble fraction was fractionated on a Biorad AG 1X8 column eluted by
      ammonium acetate pH 6 from 0.05 to 2 M. Eight retained fractions were obtained,
      containing almost exclusively GalA and Rha. Three types of oligomers could be
      identified: homogalacturonans, of which mono-,di- and tri-GalA were isolated as
      individual components, and two series of rhamnogalacturonan (RG) oligomers. One
      RG oligomer, isolated after ion-exchange chromatography, was identified as alpha
      D-GalAp-(1-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GalA p-(1-->2)-L-Rhap. The major
      peak contained oligomers of dp 6 to more than 20, of which dp 6 to 16 could be
      isolated on Bio-Gel P-6 + P-4. NMR of the oligomers of dp 6 to 10 showed the
      following structure: alpha-D-GalAp-(1[-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GalA p
      (1]n-->2)-L-Rhap. A second, quantitatively minor, series of RG oligomers eluted
      at higher ionic strength. These oligomers, which could be hydrolysed by RG
      hydrolase and RG-lyase, were based on the alternating RG structure. Their non
      reducing end was GalA, susceptible to hydrolysis by RG-galacturonohydrolase, and
      their reducing end might have more than one consecutive GalA.

PMID- 9581281
TI  - Use of a phenyl 1-selenogalactofuranoside as a glycosyl donor for the synthesis
      of galactofuranosyl-containing disaccharides.
AB  - The use of acetylated phenyl 1-seleno-beta-D-galactofuranoside as a glycosyl
      donor for the synthesis of protected D-Galf-beta-(1-->3)-alpha-D-Manp as its
      methyl or ethylthio glycoside has been demonstrated. Activation of the
      selenoglycoside over a thioglycoside acceptor by NIS/TfOH is extremely selective
      and gives the ethylthio disaccharide in 91% yield. The parent disaccharide is
      found as a terminal and branched unit in the lipopeptidophosphoglycan
      oligosaccharides of the protozoan Trypanosoma cruzi, the causative agent of
      Chagas' disease.

PMID- 9581282
TI  - 4,6-di-O-benzoyl-3-O-benzyl-alpha-D-arabino-hexo-pyranos-2-ulosyl bromide: a
      conveniently accessible glycosyl donor for the expedient construction of
      diantennary beta-D-mannosides branched at O-3 and O-6.
AB  - A concise practical, large scale-adaptable six-step sequence has been developed
      for the transformation of diacetone-glucose into 4,6-di-O-benzoyl-3-O-benzyl
      alpha-D-arabino-hexopyranos-2-ulosy l bromide (7), a most useful indirect beta-D
      mannosyl donor as its blocking group pattern allows the construction of
      biologically relevant beta-D-mannosides branched at O-3 and O-6. The broad
      utility of this new ulosyl bromide 7 resides in its high anomeric reactivity, and
      in the ease and uniformity with which beta-stereocontrol can be achieved over
      both, glycosidations and carbonyl reduction of the beta-ulosides formed: Koenigs
      Knorr conditions exclusively provide beta-glycosiduloses, hydride reduction of
      their carbonyl functions proceeds with high stereoselectivities (> 20:1) in favor
      of the beta-D-mannosides. These preparatively auspicious properties are
      materialized in an efficient, straightforward synthesis of alpha-D-Manp-(1-->6)
      [alpha-D-Manp-(1-->3)]-beta-D-Manp++ +-(1-->O)-Octyl, the 3,6-O-branched core
      mannotrioside carrying an octyl spacer instead of the chitobiosyl unit.

PMID- 9581283
TI  - Sequence-specific methylation of the mouse H19 gene in embryonic cells deficient
      in the Dnmt-1 gene.
AB  - We have used Dnmtc/c ES cells that are homozygous for disruption of the DNA
      methyltransferase gene to address how de novo methylation is propagated and
      whether it is directed to specific sites in the early embryo. We examined the
      imprinted H19 gene and the specific-sequence region implicated as an "imprinting
      mark" to determine whether de novo methylation was occurring at a restricted set
      of sites. Since the "imprinting mark" was found to be methylated differentially
      at all stages of development, we reasoned that the sequence may still be a target
      for the de novo methylation activity found in the Dnmtc/c cells, even though the
      loss of maintenance the methylase activity renders the H19 promoter active. We
      used bisulfite genomic sequencing to determine the methylation state of the
      imprinted region of the H19 gene and found a low level of DNA methylation at
      specific single CpG sites in the upstream region of the imprinted H19 sequence in
      the Dnmtc/c mutant ES cells. Moreover, these CpG sites appeared to be favoured
      targets for further de novo methylation of neighbouring CpG sites in rescued ES
      cells, which possess apparently normal maintenance activity. Our data provide
      further evidence for a separate methylating activity in ES cells and indicate
      that this activity displays sequence specificity.

PMID- 9581284
TI  - Control of gene expression in Xenopus early development.
AB  - We examine the control of gene expression before and through the MBT in Xenopus
      laevis. The generalized repression of transcription that occurs before the
      midblastula transition (MBT) is regulated by a dynamic competition between
      chromatin and transcription complex assembly. Conditions favoring the access of
      basal factors (TBP) or transactivators can overcome this transcriptional
      repression. Changes in DNase I hypersensitivity patterns of the chromatin during
      early development show that it is more accessible to DNase I before the MBT (and
      by extension to other DNA interacting proteins) than after the MBT. We also show
      that at the level of genomic domains, organization of the chromatin matrix
      attachment sites is random before MBT. We propose that these three components,
      chromatin domain structure, DNA accessibility, and the transcription complex
      chromatin dynamic competition, combine to regulate transcription in the embryo
      before and through the MBT.

PMID- 9581285
TI  - Analysis of CpG islands of trophoblast giant cells by restriction landmark
      genomic scanning.
AB  - Rat trophoblast giant cells each contain at least 100 times more genomic DNA per
      nucleus than diploid cells. This unusual phenomenon appears to be of interest in
      relation to the molecular mechanism of cell differentiation and gene expression
      in the placenta. In the present study, we analyzed the CpG islands of trophoblast
      giant cells by restriction landmark genomic scanning (RLGS) using the methylation
      sensitive landmark enzymes, Not I and Bss HII. More than 1,000 and 1,900 spots
      were detected by RLGS using Not I and Bss HII, respectively, in the placental
      junctional zone, where more than 90% of genomic DNA is present in the cells with
      higher DNA content. Of these, 97% (1,009 spots) and 99% (1,911 spots) of the
      spots found in the junctional zone showed an identical pattern and identical
      intensity with those of diploid cell controls, for which genomic DNA was
      extracted from the labyrinth zone and maternal kidney. Therefore, the giant cells
      are basically polyploid. More importantly, 24 tissue-specific spots were detected
      by RLGS using Not I. Subsequent cloning and sequencing of four typical spots of
      the genomic DNA confirmed that these DNA fragments contained abundant CpG
      dinucleotides and showed characteristics of CpG islands. Of these 24 spots, there
      were ten spots specific for the placenta, and three of them were specific for the
      junctional zone, indicating that methylation status of CpG islands in the
      placental tissue differed between the junctional zone and labyrinth zone. These
      results suggest that multiple rounds of endoreduplication and modification of CpG
      islands by cytosine methylation occur during the differentiation process of giant
      cells.

PMID- 9581286
TI  - A juvenile hormone agonist reveals distinct developmental pathways mediated by
      ecdysone-inducible broad complex transcription factors.
AB  - Juvenile hormone (JH) is an important regulator of insect development that, by
      unknown mechanisms, modifies molecular, cellular, and organismal responses to the
      molting hormone, 20-hydroxyecdysone (20E). In dipteran insects such as
      Drosophila, JH or JH agonists, administered at times near the onset of
      metamorphosis, cause lethality. We tested the hypothesis that the JH agonist
      methoprene acts by interfering with function of the Broad Complex (BRC), a 20E
      regulated locus encoding BTB/POZ-zinc finger transcription factors essential for
      metamorphosis of many tissues. We found that methoprene, administered by feeding
      or by topical application, disrupts the metamorphic reorganization of the central
      nervous system, salivary glands, and musculature in a dose-dependent manner. As
      we predicted, methoprene phenocopies a subset of previously described BRC
      defects; it also phenocopies Deformed and produces abnormalities not associated
      with known mutations. Interestingly, methoprene specifically disrupts those
      metamorphic events dependent on the combined action of all BRC isoforms, while
      sparing those that require specific isoform subsets. Thus, our data provide
      independent pharmacological evidence for the model, originally based on genetic
      studies, that BRC proteins function in two developmental pathways. Mutations of
      Methoprene-tolerant (Met), a gene involved in the action of JH, protect against
      all features of the "methoprene syndrome." These findings have allowed us to
      propose novel alternative models linking BRC, juvenile hormone, and MET.

PMID- 9581287
TI  - Prenatal onset of axonopathy in Dystonia musculorum mice.
AB  - Dystonia musculorum (dt) is a recessive hereditary neuropathy of the mouse.
      Affected animals display loss of limb coordination and twisting of the trunk.
      Sensory nerve fibers of these mice are severely reduced in number, and the
      remaining fibers present numerous axonal swellings. The gene defective in dt,
      dystonin (Dst), encodes a cytoskeletal linker protein that forms the bridge
      between F-actin and intermediate filaments. Dst is expressed during
      embryogenesis, whereas overt phenotype in dt mice only appears during the second
      week after birth. Here we show that axonal swellings are present in sensory nerve
      fibers of dt embryos as early as E15.5, before myelination and radial axonal
      growth have begun. Thus disease progression is gradual in dt mice, having begun
      during embryogenesis. In dt embryos, microtubule network disorganization and
      cytoplasmic organelle accumulation within axonal swellings were consistently
      observed. In addition, a few of the axonal swellings presented intermediate
      filament accumulation. These results demonstrate that dystonin is required for
      cytoskeleton organization during axonogenesis. They also suggest that axonal
      transport defects, through microtubule network perturbation, may be the primary
      mechanism of neurodegeneration in dt mice.

PMID- 9581288
TI  - The ultraspiracle gene of the spruce budworm, Choristoneura fumiferana: cloning
      of cDNA and developmental expression of mRNA.
AB  - Cloning and characterization of a Choristoneura fumiferana ultraspiracle (Cfusp)
      cDNA are described. First, a PCR fragment and then a cDNA clone (4.4 kb) were
      isolated from spruce budworm cDNA libraries. Comparison of the deduced amino acid
      sequence of this cDNA with the sequences in Genbank showed that this sequence had
      high homology with the ultraspiracle cDNAs cloned from Drosophila melanogaster
      (Dmusp), Bombyx mori (Bmusp), Manduca sexta (Msusp), and Aedes aegypti (Aausp).
      The Cfusp cDNA contained all the regions that are typical for a steroid/thyroid
      hormone receptor superfamily member. The DNA binding domain or C region was the
      most conserved sequence among all the usps. The A/B, D, and E regions also showed
      high amino acid identity with the amino acid sequences of Dmusp, Msusp, Bmusp,
      and Aausp. The Cfusp 4.5-kb mRNA was present in the embryos, in all larval
      stages, and in the pupae. The Cfusp mRNA levels in the midgut increased during
      the sixth-instar larval development and reached peak levels during the
      ecdysteroid raises for the pupal molt. However, Cfusp mRNA levels remained
      unchanged in the midgut of fifth-instar larvae, and in the epidermis and fat body
      of sixth-instar larvae indicating both a tissue- and stage-specific regulation of
      Cfusp mRNA expression.

PMID- 9581289
TI  - In vitro biosynthesis of poly(3-hydroxybutyric acid) by using purified
      poly(hydroxyalkanoic acid) synthase of Chromatium vinosum.
AB  - Purified recombinant poly(hydroxyalkanoic acid) (PHA) synthase from Chromatium
      vinosum (PhaECCv) was used to examine in vitro the specific synthase activity,
      turnover of R-(-)-3-hydroxybutyryl coenzyme A (3HB-CoA) and poly(3-hydroxybutyric
      acid) formation under various conditions. The 3HB-CoA consumption was terminated
      by a reaction-dependent inactivation of the PHA synthase. Salts (MgCl2, CaCl2,
      NaCl), proteins (bovine serum albumin, lysozyme, phasine) or detergent (Tween 20)
      increased the 3HB-CoA turnover to 2.5-fold. Specific PHA synthase activity was
      only partially affected by the added components. In general, a higher
      concentration of salt often inhibited the activity of PhaECCv without affecting
      the yield according to 3HB-CoA turnover. NAD+ and NADP+ (2 mM) inhibited PhaECCv
      completely, whereas NADH and NADPH did not. Macroscopic poly(3HB) granules were
      formed in vitro if PhaECCv was incubated in the presence of sufficient amounts of
      3HB-CoA and if MgCl2 was present. The form and size of the granules synthesized
      in vitro were affected by the concentration of the PHA synthase protein as well
      as by bovine serum albumin and the GA24 protein, a poly(3HB)-granule-associated
      protein of Alcaligenes eutrophus. Scanning electron micrographs from the
      synthesized granules were obtained. The granules consisted of poly(3HB) that had
      a molar mass in the range (1-2) x 10(6) g/mol.

PMID- 9581290
TI  - Molecular cloning and nucleotide sequence of the pyruvate kinase gene of an
      actinomycete Microbispora thermodiastatica.
AB  - The gene for the thermostable pyruvate kinase of Microbispora thermodiastatica
      IFO 14046, a moderate thermophilic actinomycete, was cloned in Escherichia coli.
      This gene consists of an open reading frame of 1422 nucleotides and encodes a
      protein of 474 amino acids with molecular mass of 50,805 Da. The open reading
      frame was confirmed as the pyruvate kinase gene by comparison with the N-terminal
      amino acid sequence of the purified pyruvate kinase from M. thermodiastatica.

PMID- 9581291
TI  - Cloning, sequencing and overexpression of a Rhodothermus marinus gene encoding a
      thermostable cellulase of glycosyl hydrolase family 12.
AB  - A gene library from the thermophilic eubacterium Rhodothermus marinus, strain ITI
      378, was constructed in pUC18 and transformed into Escherichia coli. Of 5400
      transformants, 3 were active on carboxymethylcellulose. Three plasmids conferring
      cellulase activity were purified and were all found to contain the same cellulase
      gene, celA. The open reading frame for the celA gene is 780 base pairs and
      encodes a protein of 260 amino acids with a calculated molecular mass of 28.8
      kDa. The amino acid sequence shows homology with cellulases in glycosyl hydrolase
      family 12. The celA gene was overexpressed in E. coli when the pET23, T7 phage
      RNA polymerase system was used. The enzyme showed activity on
      carboxymethylcellulose and lichenan, but not on birch xylan or laminarin. The
      expressed enzyme had six terminal histidine residues and was purified by using a
      nickel nitrilotriacetate column. The enzyme had a pH optimum of 6-7 and its
      highest measured initial activity at 100 degrees C. The heat stability of the
      enzyme was increased by removal of the histidine residues. It then retained 75%
      of its activity after 8 h at 90 degrees C.

PMID- 9581292
TI  - Molecular breeding of the basidiomycete Coprinus cinereus strains with high
      lignin-decolorization and -degradation activities using novel heterologous
      protein expression vectors.
AB  - Two chromosome-integrating vectors, pLC1 and pLC2, were used. The former is the
      pUC19-based vector carrying the Lentinus edodes ras gene promoter and priA gene
      terminator, and the latter is the pBR322-based vector carrying the promoter and
      terminator of the priA gene. The manganese (II) peroxidase (MnP) cDNA (mnpc)
      derived from Pleurotus ostreatus was fused between the promoter and terminator of
      pLC1 and pLC2, yielding the recombinant plasmids pLC1-mnp and pLC2-mnp. These
      plasmids were introduced into protoplasts of the Coprinus cinereus trp1 strain
      with the C. cinereus TRP1-containing plasmid pCc1001 by co-transformation. Two
      Trp+ transformants for each plasmid, showing clearly higher lignin-decolorization
      activities, were obtained through introduction of pLC1-mnp and pLC2-mnp. Southern
      blot analysis revealed that the four transformants all possess the mnpc sequence
      on their chromosomes. One Trp+ MnP+ transformant (named TF2-7), which was derived
      from the introduction of pLC2-mnp and carried the highest number of copies
      (approx. 10) of mnpc, showed remarkably high lignin-decolorization and 
      degradation activities; at the time of cultivation when only 35%-40% of the
      lignin was decolored and degraded by the control Trp+ transformant obtained by
      the introduction of pCc1001 alone, almost all of the lignin was decolored and
      degraded by TF2-7.

PMID- 9581293
TI  - Peroxisomal beta-oxidation activities and gamma-decalactone production by the
      yeast Yarrowia lipolytica.
AB  - gamma-Decalactone is a peachy aroma compound resulting from the peroxisomal beta
      oxidation of ricinoleic acid by yeasts. The expression levels of acyl-CoA oxidase
      (gene deletion) and 3-ketoacyl-CoA thiolase activities (gene amplification on
      replicative plasmids) were modified in the yeast Yarrowia lipolytica. The effects
      of these modifications on beta-oxidation were measured. Overexpression of
      thiolase activity did not have any effect on the overall beta-oxidation activity.
      The disruption of one of the acyl-CoA oxidase genes resulted in an enhanced
      activity. The enhancement led to an increase of overall beta-oxidation activity
      but reduced the gamma-decalactone production rates. This seemed to indicate a non
      rate-limiting role for beta-oxidation in the biotransformation of ricinoleic acid
      to gamma-decalactone by the yeast Yarrowia lipolytica. All strains produced and
      then consumed gamma-decalactone. We checked the ability of the different strains
      to consume gamma-decalactone in a medium containing the lactone as sole carbon
      source. The consumption of the strain overexpressing acyl-CoA oxidase activity
      was higher than that of the wild-type strain. We concluded that peroxisomal beta
      oxidation is certainly involved in gamma-decalactone catabolism by the yeast Y.
      lipolytica. The observed production rates probably depend on an equilibrium
      between production and consumption of the lactone.

PMID- 9581294
TI  - Efficient secretion of Trichoderma reesei cellobiohydrolase II in
      Schizosaccharomyces pombe and characterization of its products.
AB  - A cbh2 cDNA encoding Trichoderma reesei QM9414 cellobiohydrolase II, located on
      the expression vector whose copy number is controlled by the level of gentamicin,
      was successfully expressed under the control of a human cytomegalovirus promoter
      in the fission yeast. Schizosaccharomyces pombe. The 24-amino-acid leader peptide
      of the cbh2 gene was recognized by the yeast, enabling the efficient secretion of
      the heterologous cellobiohydrolase. The transformed S. pombe strain produced over
      115 micrograms cellobiohydrolase proteins/ml rich medium supplemented with malt
      extract and 100 micrograms/ml gentamicin. The molecular masses of the recombinant
      cellobiohydrolases, secreted as two molecular species, were estimated to be 70
      kDa and 72 kDa by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS
      PAGE). Deglycosylation treatments revealed that the recombinant enzymes were
      overglycosylated and scarcely susceptible to alpha-mannosidase. The recombinant
      enzymes showed no carboxymethylcellulase activity, but showed similar
      characteristics to those of a native enzyme purified from T. reesei in their
      optimum pH and temperature, pH and temperature stabilities, and Vmax values
      toward phosphoric-acid-swollen cellulose as substrate, except that their Km
      values were about four-fold higher than that of the native enzyme.

PMID- 9581295
TI  - Protein secretion in phosphate-limited cultures of Bacillus subtilis 168.
AB  - The secretion of proteins from Bacillus subtilis was studied under
      physiologically well-defined conditions in continuous cultures at a range of
      specific growth rates. The kinetics of secretion was analysed by using pulse
      chase and immunoprecipitation techniques that allowed both processing and release
      to be monitored. Growth conditions were selected that were known to lead to
      significant changes in the anionic polymer composition of the cell wall. Under
      magnesium limitation only low levels of native proteins were released into the
      growth medium. In contrast, much higher amounts of released protein were observed
      under phosphate limitation. Although synthesis of native secretory proteins
      appeared to be highly regulated, only minor changes in the secretion of
      heterologous proteins were detected. Comparable kinetics of protein release of
      cells grown under different conditions indicated similar cell wall
      permeabilities. The large changes in the amounts of released proteins were not
      reflected in the production of chaperones and components required fro protein
      secretion. The data suggest that the capacity of the secretion machinery is not a
      major limiting step in the export of native secretory proteins.

PMID- 9581296
TI  - Efficient production of polyhydroxyalkanoates from plant oils by Alcaligenes
      eutrophus and its recombinant strain.
AB  - The ability of Alcaligenes eutrophus to grow and produce polyhydroxyalkanoates
      (PHA) on plant oils was evaluated. When olive oil, corn oil, or palm oil was fed
      as a sole carbon source, the wild-type strain of A. eutrophus grew well and
      accumulated poly(3-hydroxybutyrate) homopolymer up to approximately 80% (w/w) of
      the cell dry weight during its stationary growth phase. In addition, a
      recombinant strain of A. eutrophus PHB-4 (a PHA-negative mutant), harboring a PHA
      synthase gene from Aeromonas caviae, was revealed to produce a random copolyester
      of 3-hydroxybutyrate and 3-hydroxyhexanoate from these plant oils with a high
      cellular content (approximately 80% w/w). The mole fraction of 3-hydroxyhexanoate
      units was 4-5 mol% whatever the structure of the triglycerides fed. The
      polyesters produced by the A. eutrophus strains from olive oil were 200-400 kDa
      (the number-average molecular mass). The results demonstrate that renewable and
      inexpensive plant oils are excellent carbon sources for efficient production of
      PHA using A. eutrophus strains.

PMID- 9581297
TI  - Recalcitrance of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene to degradation by
      pure cultures of 1,1-diphenylethylene-degrading aerobic bacteria.
AB  - 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) is the peri-chlorinated
      derivative of 1,1-diphenylethylene (DPE). Biodegradation of DDE and DPE by
      bacteria has so far not been shown. Pure cultures of aerobic bacteria involved in
      biodegradation of styrene and polychlorinated biphenyls (PCB) were therefore
      screened for their ability to degrade or cometabolize DPE and DDE. Styrene
      metabolizing bacteria (Rho-dococcus strains S5 and VLB150) grew with DPE as their
      sole source of carbon and energy. Polychlorinated-biphenyl-degrading bacteria
      (Pseudomonas fluorescens and Rhodococcus globerulus) were unable to degrade DPE
      even in the presence of an easily utilizable cosubstrate, biphenyl. This is the
      first report of the utilization of DPE as sole carbon and energy source by
      bacteria. All the tested bacteria failed to degrade DDE when it was provided as
      the sole carbon source or in the presence of the respective degradable
      cosubstrates. DPE transformation could also be detected in cell-free extracts of
      Rhodococcus S5 and VLB150, but DDE was not transformed, indicating that cell wall
      and membrane diffusion barriers were not limiting biodegradation. The results of
      the present study show that, at least for some bacteria, the chlorination of DDE
      is the main reason for its resistance to biodegradation by styrene and DPE
      degrading bacteria.

PMID- 9581298
TI  - HIV neuropathogenesis and therapeutic strategies.
AB  - Human immunodeficiency virus (HIV)-1 neuropathogenesis can be divided into three
      important components: (i) virus entry into the nervous system; (ii) the role of
      viral proteins and/or cellular products in neural tissue damage; (iii) the
      mechanisms of neuronal injury/death. Both blood derived macrophages or
      trafficking HIV-1 infected T-lymphocytes have been implicated in viral entry to
      the central nervous system (CNS). The major cell type harboring productive HIV-1
      infection in the nervous system is the perivascular macrophage/microglia. The HIV
      1 infection of brain astrocytes, restricted to the expression of regulatory gene
      products, may cause astrocyte dysfunction and contribute to neuronal injury or to
      disruption of the blood-brain barrier (BBB). Studies of cerebrospinal fluid and
      postmortem tissues reveal chronic inflammation/immune activation in the nervous
      system during the later stages of HIV-1 infection associated with disruption of
      BBB integrity. Blood-brain barrier damage may underlie the white matter pallor
      described in HIV-1 infection and could result in further entry into the CNS of
      toxic viral or cellular products, or additional HIV-1 infected cells. The HIV
      infected and activated macrophages/microglia produce excessive amounts of pro
      inflammatory cytokines, including tumor necrosis factor alpha, and platelet
      activating factor. These products are directly toxic to human neurons in vitro.
      The HIV-1 envelope glycoprotein, gp 120 may stimulate the release of toxic
      factors from brain macrophages. Blocking N-methyl-D-aspartate (NMDA; or AMPA)
      glutamate receptors can antagonize candidate toxins of both viral and cellular
      origin. It has been postulated that (weak) excitotoxicity leads to oxidative
      stress in neurons and ultimately to apoptosis. Neuronal apoptosis occurs in the
      brains of both children and adults with HIV-1 infection. This understanding of
      HIV neuropathogenesis implies that therapeutic strategies should include: (i)
      anti-retroviral medications to decrease systemic and CNS virus load, and possibly
      to prevent perinatal transmission of HIV; (ii) anti-inflammatory compounds to
      decrease the chronic immune activation in microglia and allow the restoration of
      BBB integrity; and (iii) neuroprotective compounds to reduce neuronal injury and
      apoptotic death.

PMID- 9581299
TI  - Incidence of thrombocytopenia in infants born to mothers with idiopathic
      thrombocytopenic purpura.
AB  - Neonatal thrombocytopenia related to maternal idiopathic thrombocytopenic purpura
      (ITP) is reportedly uncommon but may have severe complications. The present
      report reviews records of 15 infants born to mothers with ITP during a 10-year
      period, and the incidence of neonatal thrombocytopenia and the risk of
      hematological complications is examined. Severe thrombocytopenia (platelets <
      50,000/microL) was seen in three infants despite successful therapy with high
      dose gamma globulin prior to delivery, which elevated maternal platelet counts.
      Although the platelet counts of these three infants fell to < 10,000/microL, none
      had severe complications. Moreover, no infants required treatment such as
      adrenocorticosteroids, platelets transfusion, or high doses of gamma globulin. No
      maternal markers predicted the degree of neonatal thrombocytopenia. The risk of
      complications arising from neonatal thrombocytopenia is low, but careful
      observation is required for the thrombocytopenic newborn of ITP mothers even when
      the infant has no bleeding complications at delivery.

PMID- 9581300
TI  - Ionized magnesium level in whole blood of healthy Japanese children.
AB  - Magnesium (Mg) catalyzes or activates more than 300 enzymes in the body, and it
      plays a pivotal role in the metabolism of carbohydrates, fats and proteins. Until
      recently Mg has only been measured as a total substance concentration; however,
      it is the free ionized form of magnesium (iMg2+) that is physiologically active.
      In 1992, a novel ion selective electrode (ISE) utilizing a neutral carrier-based
      membrane for assessment of iMg2+ in whole blood, plasma or serum was designed and
      it was used to measure the iMg2+ level in whole blood of 160 healthy Japanese
      children. There was a significant positive correlation between serum total
      magnesium (SMg) and iMg2+. Percent ionized magnesium (iMg2+/SMg) was 58.3 +/-
      4.1% and increased with growth (age and bodyweight). The level of iMg2+ was 1.29
      +/- 0.08 mg/dL (range, 1.09-1.51) ?0.535 +/- 0.033 mmol/L (range, 0.452-0.627)?
      and was constant irrespective of growth. On the other hand, SMg, serum total
      calcium (SCa) and ionized calcium (iCa2+) decreased with growth. Thus only iMg2+
      level was constant irrespective of growth. It is suspected that the buffer action
      of protein binding Mg may keep the iMg2+ level constant, because iMg2+ plays an
      important part in the activation of many enzymes.

PMID- 9581301
TI  - Helicobacter pylori-dependent intragastric urea biodegradation in children:
      diagnostic and pathogenetic importance.
AB  - The objective of the present work was to study the relationship between
      intragastric urea hydrolysis generated by Helicobacter pylori urease and acid
      peptic disease in childhood. Intragastric urease activity was examined by urea
      and ammonia concentration measurement in gastric juice in 91 children with upper
      abdominal complaints. Helicobacter pylori infection was detected from 70 (76.9%)
      of 91 patients, including all of the 15 subjects with peptic ulcer disease.
      Helicobacter pylori-related gastritis in children was associated with a decrease
      of urea and an increase of ammonia in gastric juice (P < 0.001) in comparison
      with H. pylori-negative children. The gastritis score was correlated with the
      concentrations of urea and ammonia in the gastric juice of patients infected with
      H. pylori. There was a significant correlation between the histologically
      detected dissemination of organisms and gastric ammonia levels. Similar results
      were obtained concerning correlation between gastric juice ammonia and anti-H.
      pylori specific immunoglobulin G versus highly purified antigen of H. pylori
      containing urease. Present findings prove that H. pylori plays an essential role
      in the pathogenesis of gastritis and that ammonia is one of the main pathogenic
      factors of acid-peptic disease.

PMID- 9581302
TI  - Comparative efficacy of cefixime and ampicillin-sulbactam in shigellosis in
      children.
AB  - Shigellosis is still an important health problem in developing and underdeveloped
      countries as it is resistance to commonly used antibiotics including ampicillin,
      trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline. Between May 1996
      and October 1996, in a prospective randomized double-blind trial, cefixime was
      compared with ampicillin-sulbactam, both given orally for a period of 5 days, for
      the treatment of 80 children with acute bloody diarrhea. Forty patients were
      treated with a single-dose (8 mg/kg per day) of cefixime and the other 40
      patients were given three doses of 100 mg/kg per day of ampicillin-sulbactam.
      After identification of Shigella organisms in stool specimens, nine patients in
      the cefixime receiving group and six patients in the ampicillin-sulbactam
      receiving group were excluded from the study. Differences in average age, sex and
      weight between the cefixime and ampicillin-sulbactam group were statistically
      meaningless (P > 0.05). Fever and bloody diarrhea were universal features. The
      efficacy of cefixime was found to be better than ampicillin-sulbactam. Patients
      given cefixime had a shorter duration of fever (P < 0.01), shorter duration to
      disappearance of blood in the stool (P < 0.01), reduced time with diarrhea (P <
      0.01) and reduced hospitalization time during the 5 study days (P < 0.01) than
      patients given ampicillin-sulbactam. No adverse effects were observed in the two
      study groups. This controlled trial showed good efficacy with cefixime compared
      to ampicillin-sulbactam in the treatment of shigellosis. Single-dose daily oral
      therapy with cefixime also showed good tolerability. Cefixime should be
      considered as an alternative drug of choice for shigellosis in children.

PMID- 9581304
TI  - Magnetic resonance imaging of acute cerebellar ataxia: report of a case with
      gadolinium enhancement and review of the literature.
AB  - A 10-year-old girl exhibited severe cerebellar ataxia following acute
      enterocolitis, and was diagnosed as having acute cerebellar ataxia (ACA). MRI of
      the brain in the acute stage revealed moderate swelling of the cerebellum and
      abnormal signal intensity enhanced with gadolinium in the cerebellar hemisphere.
      This is the first report of an ACA case with positive gadolinium enhancement.
      Cases of ACA with MRI abnormalities are reviewed and the clinical entity of ACA
      is discussed in association with autoimmune encephalitis.

PMID- 9581303
TI  - Acute bronchodilatory effect of salmeterol on methacholine-induced
      bronchoconstriction in childhood asthma.
AB  - A review of the literature highlights the need for research, particularly on the
      acute bronchodilatory effect of salmeterol on bronchoconstriction in the
      pediatric age group. The present study attempted to evaluate the acute
      bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction
      in childhood asthma and to compare it with the effect of salbutamol. Forty-four
      asymptomatic children with mild-to-moderate asthma (23 boys and 21 girls; aged 7
      17 years) were studied. At the beginning, the baseline forced expiratory volume
      in 1 s (FEV1) was measured, and the methacholine challenge was performed by
      doubling the dose to determine PC20 (provocative concentration of inhaled
      methacholine required to reduce FEV1 by 20%). At the same time, the
      transcutaneous arterial oxygen saturation (SaO2) was also measured. Each subject
      inhaled a single dose of 25 micrograms salmeterol (n: 23, group I) or 100
      micrograms salbutamol (n: 21, group II) following the SaO2 measurement. The same
      measurements (FEV1, SaO2) were repeated 5 and 20 min after the inhalation. After
      inhalation of salmeterol or salbutamol, the differences between the values of
      FEV1 and SaO2 after 5 and 20 min were insignificant in both group I and group II
      (P > 0.05), although there was a significant improvement in both FEV1 and SaO2
      after 5 and 20 min (P < 0.005). From these findings it was concluded that
      salmeterol can be considered as effective as salbutamol on methacholine-induced
      bronchoconstriction.

PMID- 9581305
TI  - Hypokalemic paralysis in association with acute gastroenteritis: a report of a
      sporadic case.
AB  - Hypokalemic periodic paralysis is a condition, characterized by episodic weakness
      of the skeletal muscle. It may be presented as familial or sporadic (secondary).
      In sporadic cases, the patient may present with paralysis without any previous
      self or familial history. It is known that these patients are more susceptible to
      hypokalemia than normal individuals. In low serum K+ concentrations that the
      normal population can tolerate, these patients may easily suffer from paralysis.
      A sporadic case of hypokalemic quadriparesis associated with acute
      gastroenteritis without any self or family history is reported. The patient had
      experienced two episodes of quadriparesis within a short interval and responded
      dramatically to potassium replacement therapy.

PMID- 9581306
TI  - Central diabetes insipidus as a complication of neonatal pathology: report of
      three cases.
AB  - Three patients, 11, 17 and 41 days old with various degrees of central nervous
      system (CNS) lesions developed central diabetes insipidus as a complication of
      hypothalamic damage. Two of the children had congenital CNS malformations
      including meningomyelocele, hydrocephalus, and prosencephaly, while the third
      child presented Streptococcus agalactiae meningitis, complicated with CNS
      hemorrhage and hypertensive dilatation of the lateral ventricles. All of them
      fulfilled the criteria for central diabetes insipidus, reaching high levels of
      serum sodium and osmolality, along with hypotonic urine. The responses to
      intranasal arginine-vasopressin were prompt, normalizing the serum levels of
      sodium and increasing urinary osmolality, allowing a better metabolic balance,
      avoiding continuing damage to the already compromised CNS. The neonatologist must
      be aware of the possibility of this kind of complication even in a normal child
      with CNS infection. Imaging studies showing hemorrhage in the region of the
      posterior hypothalamus must be a sign that this type of complication is able to
      occur.

PMID- 9581308
TI  - Inhaled nitric oxide therapy via nasopharyngeal tube in an infant with end-stage
      pulmonary hypertension.
AB  - The delivery of nitric oxide (NO) via a nasopharyngeal tube is an alternative to
      endotracheal intubation. A male infant with end-stage pulmonary hypertension (PH)
      due to a severe hypoplastic lung developed a PH crisis on day 145 and received NO
      inhalation via a nasopharyngeal tube. Clinical improvement was maintained for 7
      days with 18-22 ppm NO inhalation. The patient remained in close physical contact
      with his parents without the use of sedation. Blood methemoglobin levels remained
      below 1%. The environmental NO levels were less than 0.06 ppm and NO2 less than
      0.3 ppm throughout the treatment, well within the safety margin. On day 152, the
      patient succumbed to hypoxemia and heart failure. The use of a nasopharyngeal NO
      delivery system without sedation, as an alternative to endotracheal intubation
      with sedation, was a practical method in treating a patient with PH while
      maintaining a certain quality of life for the patient and the family.

PMID- 9581307
TI  - Neonatal intrahepatic cholestasis with hepatic siderosis and steatosis.
AB  - Neonatal intrahepatic cholestasis is a heterogeneous disease of undetermined
      cause. There is an unreported subset of idiopathic neonatal intrahepatic
      cholestasis with an unusual histological combination of hepatic siderosis and
      macrovesicular steatosis. The patients were a 34-day-old female and a 39-day-old
      male with normal birth weights. Their mothers had received oral iron supplement 4
      6 weeks before delivery. The patients had obstructive jaundice noticed at the
      well-baby clinic at 1 month of life. They had high levels of serum galactose and
      tyrosine, hyperferritinemia. Urinary organic acid and bile acid analyses were
      negative, and galactose-1-phosphate uridyltransferase activity in red cells was
      normal. Liver biopsies showed diffuse iron deposits and macrovesicular fat. By
      substituting formula milk with lactose-free milk, the patients responded, and had
      normal biochemical tests within 5 months of life. Follow-up biopsies, at the age
      of 12 months, showed mild residual fibrosis without iron or fat deposits. They
      are both well at 3 and 6 years of age, respectively, without biochemical liver
      dysfunction and neurologic impairment. Prenatal iron-overload might contribute to
      the pathogenesis of the disease, but further studies are needed to confirm the
      assumption.

PMID- 9581309
TI  - Uncommon multisystemic involvement in a case of Henoch-Schonlein purpura.
AB  - A case of Henoch-Schonlein purpura (HSP) characterized by several unusual
      complications is reported. A 10-year-old boy was hospitalized with acute abdomen
      and developed purpura on the lower extremities after 4 days of hospitalization.
      He had protein-losing enteropathy, diagnosed by an elevated fecal alpha-1
      antitrypsin clearance. The colicky abdominal pain and protein-losing enteropathy
      subsided after methylprednisolone pulse therapy was administered. He had left
      hydronephrosis and gall-bladder abnormalities detected by ultrasonography, and
      purpura nephritis. However, after improvement of these abnormalities, he showed
      steroid-induced epidural lipomatosis, detected by magnetic resonance imaging,
      which resolved with steroid reduction. Ultrasonography and magnetic resonance
      imaging were useful for detecting these uncommon multisystemic involvements in
      HSP.

PMID- 9581310
TI  - The need to establish a scientific basis for child care as a medical science.

PMID- 9581311
TI  - Child rearing and child outcomes in Japan and the UK.
AB  - Japan and the UK are compared in relation to various child health outcomes. It is
      noted that in the rates of child abuse and criminal activity, Japan is in a more
      favorable position. Rates of behavior problems and suicide rates are very similar
      in the two countries. Consideration is given to the reasons for the differences.
      The rates of single parents and divorce are much lower in Japan. The rates of
      working mothers are about the same, but Japanese women work longer hours.
      However, it is suggested that more important differences may lie in the greater
      respect for authority and emphasis on discipline and conformity in Japan. The
      effects of industrialization on family life and on child development are
      summarized. It is suggested that the separation of the adolescent age group from
      the rest of the population has had especially negative results in Western
      industrialized countries. Various suggestions are made concerning the positive
      role that pediatricians can play in promoting child development. In particular,
      pediatricians are encouraged to support and not undermine parents, to involve
      fathers in management of illness and disability, to press for full implementation
      of the United Nations Convention on the Rights of the Child, and for ready
      availability of good substitute child care facilities.

PMID- 9581312
TI  - Perinatal outcome and the social contract: interrelationships between health and
      society.
AB  - Rates of infant mortality and prematurity or low birthweight serve as indirect
      measures of the health of a nation. This paper presents current population data
      documenting the still serious problem of perinatal outcome in the USA as well as
      in other economically developed countries. International comparisons suggest that
      nations which have the greatest inequality of income and social opportunity also
      have the most adverse perinatal, child and adult health outcomes. Furthermore,
      the data assert that these effects are independent of average national wealth or
      gross national economic productivity. Health status differs by social class and
      race, even among the most affluent sectors of the population. All social classes,
      even the wealthiest, suffer the health consequences of social inequalities. An
      explanatory socio-psychological theory of causality is proposed.

PMID- 9581313
TI  - Children in Germany now.

PMID- 9581314
TI  - Child-rearing in France: the point of view of a nutritionist.

PMID- 9581315
TI  - Child rearing in Japan: current trends and problems.
AB  - Loyalty to one's extended family, a well-known Japanese tradition, has broken
      down following World War II. Child rearing in Japan, therefore, has been changing
      gradually and clearly. Traditionally, child rearing was taught to young mothers
      by the grandmothers. However, recently young couples are no longer living with
      their parents. Therefore, there are no advisers nor consultants available at home
      for their child rearing. Commercialism has certainly invaded the field of child
      rearing, including too many guidebooks and even baby-sitting companies.
      Children's lives have become much more competitive, busy and unnatural in
      comparison with those of 20-30 years ago. This might be one cause of the
      increased incidence of bullying, school phobia and psychological disorders in
      children.

PMID- 9581316
TI  - Safe use of imipenem/cilastatin in a neonatal intensive care unit.

PMID- 9581317
TI  - The right man syndrome: skepticism and alternative medicine.

PMID- 9581318
TI  - Speculating about miracles, nonlocal reality, and the nuocontinuum.

PMID- 9581319
TI  - The Getting Well program: digging deep to find healing.

PMID- 9581320
TI  - An overview of medical acupuncture.
AB  - This article defines the theoretical matrix and clinical value of the emerging
      complementary discipline of medical acupuncture, the acupuncture approach most
      commonly integrated by physicians into conventional medical practice. Medical
      acupuncture respects our contemporary understanding of neuromuscular anatomy and
      pain physiology while embracing the classical Chinese perception of a subtle
      circulation network of a vivifying force called qi. This hybrid acupuncture
      approach expresses the best of both worlds by describing a context in which to
      organize patient symptoms that usually escape attention in the standard medical
      evaluation. Musculoskeletal problems have been shown to be the most frequently
      and successfully treated disorders; however, medical acupuncture is adaptable to
      most clinical practices and can be used either as the primary or a complementary
      treatment. The physician acupuncturist can creatively intervene in a spectrum of
      medical disorders from early premorbid manifestations to chronic organic or
      musculoskeletal lesions by activating the appropriate subunit of qi circulation.

PMID- 9581322
TI  - Between lightning and thunder: the pause before the shifting paradigm.

PMID- 9581323
TI  - Complementary therapies and the medical profession: a study of medical students'
      attitudes.
AB  - BACKGROUND: Despite the popularity of complementary therapies with the public,
      knowledge and use of these therapies among doctors appear limited. However,
      studies show that physicians and medical students are positive toward
      complementary therapies and have a high level of interest in learning about them.
      METHODS: The attitudes of medical students toward complementary therapies were
      examined using a questionnaire distributed to 800 first-, third-, and fifth-year
      medical students at two universities in Melbourne, Australia. RESULTS: The survey
      revealed that whereas Australian medical students were positive toward
      complementary therapies, their self-reported knowledge was low, with 56% having
      no knowledge of the principles of complementary therapies. Attitudes toward
      different therapies were found to vary widely, with students having little
      knowledge of chiropractic and naturopathy, the two therapies most commonly used
      by Australians. Students consistently scored meditation, massage, and acupuncture
      the highest with regard to knowledge, perceived usefulness, intended patterns of
      referral after graduation, and desire for education in the undergraduate degree.
      CONCLUSIONS: When the medical course included some tuition on complementary
      therapies, students were more positive toward them. A single lecture on
      complementary therapies was found to have significant impact on medical students'
      views. Medical students have a high level of interest in complementary therapies
      that is not being satisfied by their undergraduate curricula.

PMID- 9581321
TI  - A review of mind-body therapies in the treatment of cardiovascular disease. Part
      1: Implications for the elderly.
AB  - BACKGROUND: A review of research on complementary and alternative treatments,
      specifically mind-body techniques, was conducted at Stanford University. The
      goals of the review were to establish a comprehensive literature review and to
      provide a rationale for future research concerning successful aging. METHODS:
      Computerized searches were conducted using MEDLINE, PsychInfo, Stanford Library,
      Dissertation Abstracts, Lexus-Nexus, the Internet, and interviews conducted with
      practitioners. All studies since 1990 that examined mind-body treatments of
      cardiovascular disorders in the elderly were included. Mind-body practices
      evaluated were social support, cognitive-behavioral treatment, meditation, the
      placebo effect, hope, faith, imagery, spiritual healing, music therapy, hypnosis,
      yoga, t'ai chi, qigong and aikido. Studies conducted after 1990 were a priority,
      but when more recent literature was scarce, other studies using randomized,
      controlled trials were included. RESULTS: Mind-body techniques were found to be
      efficacious primarily as complementary and sometimes as stand-alone alternative
      treatments for cardiovascular disease-related conditions. Studies provided
      evidence for treatment efficacy, but the need for further controlled research was
      evident. CONCLUSIONS: Reviewers found only a handful of randomized, controlled
      research studies conducted in the United States. As a result, there is a lack of
      replicated studies with which to determine appropriate treatment dosage and the
      mechanisms by which many of the practices work. Compelling anecdotal evidence,
      the presence of some controlled research, overall cost effectiveness, and the
      lack of side effects resulting from mind-body treatments make further
      investigation a high priority.

PMID- 9581324
TI  - Incidence of premenstrual syndrome and remedy usage: a national probability
      sample study.
AB  - CONTEXT: Premenstrual syndrome is believed to affect 30% to 80% of women. Studies
      in various cultures have used a variety of methodologies to determine prevalence,
      symptom profile, and effectiveness of available treatments. This study was
      designed to provide information on incidence of PMS and therapies used based on a
      national probability sample of US women. METHOD: In 1996 a national probability
      sample (N = 1052) of women aged 21 to 64 years was surveyed by telephone using
      random digit dial methods. The survey included demographic information, questions
      concerning respondent knowledge of premenstrual syndrome, incidence rates of
      common premenstrual syndrome symptoms, and any remedies that were used to control
      the symptoms. RESULTS: Forty-one percent of the women responded "yes" to the
      question, "Do you suffer from premenstrual syndrome?" An additional 17% indicated
      that they experienced symptoms prior to their menstrual cycle that are commonly
      associated with premenstrual syndrome (e.g., pain, bloating, feeling more
      emotional, weight gain, food cravings), though without associating these symptoms
      with premenstrual syndrome explicity. The most frequently noted severe symptom
      was that of "[feeling] more emotional." Of those reporting premenstrual syndrome
      symptoms, approximately 42% took either prescription or over-the-counter
      medications to relieve them. Eighty percent of the women taking any type of
      medication relied on over-the-counter medications. Prescription drug use for
      premenstrual syndrome symptoms focused on medications to control pain; hormone
      supplements were the second most frequently prescribed rugs. Fewer than 3% of the
      respondents used prescription medications. Respondents were asked to indicate
      whether they had used a complementary medical therapy to control symptoms.
      Exercise was used most frequently (18%), and acupuncture was the least frequently
      used. Although only a small percentage of women used complementary therapies, for
      most of these therapies a near-perfect concordance was found between usage and
      belief in efficacy. CONCLUSIONS: Women were aware of symptoms related to
      premenstrual syndrome more frequently than they recognized a formalized medical
      syndrome. Less than half of the women reporting symptoms had taken either over
      the-counter or prescription drugs. Those who tried complementary therapies
      generally found them to be effective.

PMID- 9581325
TI  - Harriet Beinfield, LAc, and Efrem Korngold, LAc, OMD eastern medicine for western
      people. Interview by Bonnie Horrigan.

PMID- 9581326
TI  - In support of single-case clinical studies.

PMID- 9581327
TI  - Codex: a crisis of healthcare freedom and government regulation.

PMID- 9581328
TI  - Six second therapy.
AB  - Good general practice involves recognising the therapeutic power of the
      consultation itself. These simple acts are a way of enhancing that therapeutic
      power. Each takes around 2 seconds, so in 6 seconds we can achieve some useful
      therapy--that has to be fairly cost-effective!

PMID- 9581329
TI  - New and emerging drug treatments for hypertension.
AB  - BACKGROUND: Existing antihypertensive therapies are effective in lowering blood
      pressure, however, they are associated with adverse effects that may contribute
      to medication non-compliance. Furthermore, morbidity and mortality benefits have
      not been established with commonly used agents such as ACE inhibitors and calcium
      channel blockers. OBJECTIVE: Newer antihypertensive therapies offer similar
      efficacy with fewer adverse effects and may be of benefit in a number of
      concomitant disease states. DISCUSSION: This article examines the promise of the
      newer therapies: angiotensin II antagonists, T-type calcium channel blockers,
      dual metalloprotease inhibitors and endothelin receptor antagonists.

PMID- 9581330
TI  - 'I'm just here for my blood pressure pills, doc'.
AB  - In summary, a consultation for a blood pressure check provides the opportunity
      and obligation for a systemic review of and, when needed, the development of,
      strategies to modify risk factors which are known to expose an individual to
      greater risk of ultimately developing vascular disease.

PMID- 9581331
TI  - Common dilemmas in managing hypertension.
AB  - BACKGROUND: Undertaking a blood pressure measurement is a common occurrence in
      general practice. Excellent guidelines for the management of hypertension are
      available to all Australian general practitioners. There are, however, variants
      of primary hypertension that present management dilemmas, such as: is it ever
      safe to stop medication, the role of ambulatory blood pressure monitoring, and
      refractory or isolated systolic hypertension. OBJECTIVE: To provide management
      guidance on some of the difficult dilemmas that may occur in relation to blood
      pressure control in everyday practice while recognising the limitations of the
      application of scientific evidence to the individual presenting patient.
      DISCUSSION: Recommendations are given for the withdrawal of antihypertensive
      medication in a select group of patients. Ambulatory blood pressure monitoring is
      recommended for the patient with labile or refractory hypertension and where
      'white coat' hypertension is suspected. Management advice is given for the very
      old, the asymptomatic middle-aged man, and refractory and isolated systolic
      hypertension.

PMID- 9581332
TI  - Detecting and improving compliance. Is concordance the solution?
AB  - BACKGROUND: Despite the proven benefits of hypertension control, fewer than 50%
      of those treated for hypertension have their blood pressure adequately
      controlled. The major reason for this is poor compliance with treatment.
      OBJECTIVE: This article examines the extent of the problem, methods of detection
      and effective strategies in managing the problem of poor compliance with medical
      care with particular reference to hypertension. New ideas in the field are also
      discussed. DISCUSSION: Self-report is probably the best method of detection of
      poor compliance. Strategies of managing the problem are discussed.

PMID- 9581333
TI  - Mentally ill families. When are the children unsafe?
AB  - This article examines the impact of parental mental illness on the behaviour and
      development of children. Early identification and intervention is crucial; too
      often the child is not considered, particularly if the parent is not frankly
      abusive. Supports and aid to parenting may be crucial for mentally ill parents to
      prevent relapse and promote the child's mental health. General practitioners have
      a crucial role in this process.

PMID- 9581334
TI  - Choosing a method to answer the question. Quantitative or qualitative-
      complimentary, not competitive?
AB  - One of the defining characteristics of general practice is its heterogeneity. GPs
      vary widely in their assessment and management of clinical problems. It is
      therefore likely that this environment will generate numerous questions that
      require the use of various research approaches. This paper discusses how to
      choose between these approaches.

PMID- 9581335
TI  - Augmentation of Pap smear screening of high risk aboriginal women. Use of a
      computerised process tool within the Broome Aboriginal Medical Service.
AB  - OBJECTIVE: The Broome Regional Aboriginal Medical Service (BRAMS) in Broome,
      Western Australia, conducted a 4 month program to augment the Pap smear screening
      of Aboriginal women. The emphasis was on those with a past history of abnormal
      smears, aged greater than 40 years, living in remote communities and very (more
      than 5 years) overdue. METHOD: Continuation of existing opportunistic recall
      processes supplemented by three components: the development of an Aboriginal
      Health Worker (AHW) run Pap smear clinic; the provision of Aboriginal outstation
      screening; and active recruitment of targeted women (by AHW staff) using
      worklists. All components used Healthplanner, a computerised process tool to
      facilitate targeting and recall. MAIN OUTCOME MEASURES: The number of Pap smears
      taken from the target groups before and after intervention and the proportion
      screened from the women eligible in each target group at the start of the
      program. RESULTS: There was statistically significant increase in the coverage of
      Aboriginal women overall, those over the age of 40 years, and those from remote
      communities when compared with the same period the previous years. In 4 months,
      21-30% of Aboriginal women eligible for Pap smears in these high risk categories
      including those with past abnormal smears were screened. Over-screening of women
      did not occur as only 4% of smears taken were from women screened less than 12
      months previously. Smears taken by AHW staff were of high quality. CONCLUSION:
      Use of a computerised process tool in a remote setting can facilitate selective
      recruitment of high risk women overdue for Pap smears.

PMID- 9581337
TI  - Management of a sore throat. Antibiotics are no longer appropriate.
AB  - Evidence is mounting that antibiotics have little impact on the duration of sore
      throat symptoms, regardless of aetiology. Complications of sore throat are now so
      rare that an adverse drug reaction from antibiotic therapy is more likely.

PMID- 9581336
TI  - Scars. Can they be minimised?
AB  - To produce a wound either accidentally (trauma) or intentionally (surgically)
      takes only a few moments. The subsequent process of healing to produce the final
      scar takes up to 1 year to complete and is dependent on many factors. An
      understanding of the nature of wound healing, the factors influencing it and how
      to modify these factors will allow you to produce the 'best' scar. Ideal
      conditions for best scarring include: accurate apposition of wound edges; sutures
      under minimal tension; everted skin edges; placing the wound in 'Langer's lines'
      or lines of election; adequately supporting the wound; ensuring the wound is free
      from infection or haematoma.

PMID- 9581338
TI  - A punch injury.

PMID- 9581339
TI  - Painful knees. Finding the cause.

PMID- 9581341
TI  - Tennis elbow ... or is it?

PMID- 9581340
TI  - A severe facial rash.

PMID- 9581342
TI  - Practice tip. Simple cure for the ingrown toenail.

PMID- 9581343
TI  - Consider toxic as well as allergic effects of insect stings.

PMID- 9581344
TI  - Jumper ants don't bite they sting.

PMID- 9581345
TI  - [Generation and characterization of avian vitelline antibodies against
      lipopolysaccharide and lipid A. 1. Induction and preparation of specific egg yolk
      antibodies (IgY) against endotoxins].
AB  - The immunisation of mammals with LPS- and lipid A-antigens leads to the
      production of specific antibodies. In the present study, we describe the
      generation and preparation of antibodies from egg yolks of immunized chickens.
      Egg yolk antibodies were raised by immunizing laying hens with five LPS- and
      three lipid A-preparations from various gram-negative bacteria species in
      different immunisation protocols. Antibodies from collected egg yolks were
      extracted and purified by means of several standard methods. The purity of
      antibody-preparations was measured and compared by SDS-PAGE. Specific antibodies
      were assayed by two different EIA procedures. It could be shown that the
      immunisation of hens with LPS- and lipid A-Antigens resulted in the production of
      specific egg yolk antibodies, regardless of immunisation-scheme and amount of
      antigen.

PMID- 9581346
TI  - [Generation and characterization of avian vitelline antibodies against
      lipopolysaccharide and lipid A. 2. Investigations of specificity of egg yolk
      antibodies (IgY) against endotoxin].
AB  - Various preparations of egg yolk antibodies against different endotoxins of gram
      negative bacteria were characterized with regard to their immunological
      properties. To do this, we investigated the reactivity of antibodies against a
      number of lipopolysaccharides and lipid-A by enzyme-immuno-assays and immunoblot.
      It could be shown that all antibody preparations contained specific antibodies,
      reactive with their homologous antigen. Furthermore these antibodies showed cross
      reactivity with structural diverse LPS- and lipid A-antigens from different
      sources. Anti lipid A-antibodies appeared to be highly crossreactive with
      purified LPS and lipid A from several gram-negative organisms. Egg yolk
      antibodies raised by immunization with LPS showed cross-reactivity with
      enterobacterial LPS and only marginal reactivity with both LPS from other gram
      negative bacteria and lipid A. The results from immunoblot experiments confirmed
      our findings from EIA-studies.

PMID- 9581347
TI  - [Intraocular and serum antibody titers to Leptospira in 150 horses with equine
      recurrent uveitis (ERU) subjected to vitrectomy].
AB  - Between February 1993 and July 1997, 150 horses suffering from recurrent uveitis
      were subjected to parsplana vitrectomy. In these horses, antibody titers to
      Leptospira serovars were determined in serum samples and in samples from diluted
      vitreous collected during vitrectomy. Although the vitreous samples were diluted
      with 250 ml of balanced salt solution, in 86 of the 150 vitreous samples (= 57%)
      the antibody titers were higher than in the serum samples. Additionally, serum
      samples from 77 horses suffering from ERU, but which were not subjected to
      vitrectomy, and serum samples from 97 horses with clinically normal eyes were
      analyzed for antibodies to Leptospira serovars. Among the 227 horses with ERU
      (150 treated surgically, 77 treated conservatively) 50 horses (50 of 227 = 22%)
      had serum antibody titers to Leptospira serovars of > or = 1:800. Among the 97
      horses with clinically normal eyes, 24 horses (24 of 97 = 25%) had serum antibody
      titers to Leptospira serovars of > or = 1:800. In undiluted vitreous samples from
      20 horses with clinically normal eyes, no antibody titers to Leptospira serovars
      could be detected. Among the 150 horses with ERU, 90 animals (90 of 150 = 60%)
      had antibody titers of > or = 1:100 in the diluted vitreous samples, the
      difference being highly significant (p < 0.001). The findings are discussed in
      relation to the etiology of recurrent uveitis in horses.

PMID- 9581348
TI  - Isolation of fowl adenoviruses serotype 4 from pigeons with hepatic necrosis.
AB  - Nine homogenized livers were taken to isolate the causative agent of adenovirus
      type I and type II infections in pigeons. The samples were passaged up to four
      times on primary chicken embryo hepatocytes. Adenoviruses were isolated from all
      of the six type II but none of the three type I infections. Serologically the
      isolated adenoviruses were classified as fowl adenovirus (FAV) serotype 4.
      Restriction enzyme analysis of two isolates in comparison with FAV4 reference
      strain KR5 confirmed the serological results and classification of the pigeon
      isolates as FAV4 strains.

PMID- 9581349
TI  - Current status on the laboratory diagnosis of Ornithobacterium rhinotracheale
      "ORT" in poultry.
AB  - Respiratory disease conditions are one of the most serious groups of diseases
      affecting poultry. Ornithobacterium rhinotracheale by has recently been
      recognized in many countries. Clinical signs and lesions are of little value in
      diagnosis. Accurate diagnosis must be substantiated by isolation and
      identification of the causative bacteria and/or detection of antibodies using
      serological examination. In the present paper a review on the current status of
      ORT laboratory diagnosis, results of serotyping of field isolates, serological
      surveillance in poultry flocks as well as the role of other avian pathogens in
      course of ORT infection will be given.

PMID- 9581350
TI  - Arginine in liquid contents of displaced abomasal in dairy cows.
AB  - Increased nitric oxide synthesis by abomasal neurons was related to disorders of
      abomasal muscle function in displaced abomasum in a previous study. Nitric oxide
      is synthesised from L-arginine. The objectives of the studies reported on here
      were to isolate factors associated with arginine in abomasal fluid and to
      evaluate the association between arginine in abomasal fluid and left displaced
      abomasum (LDA), right displaced abomasum (RDA) or abomasal volvulus (AV). Four
      cows fitted with abomasal cannulas were fed two different diets in succession.
      Abomasal samples were taken from 1.00 a.m. to 11.00 p.m. during each diet. The
      data were analyzed using three factor analysis of variance. Diet, sampling time
      and cow were significantly associated with abomasal arginine concentration. Diet
      and cow significantly affected abomasal arginine percentage, whereas sampling
      time had no significant effect. Cows diagnosed with LDA, RDA or AV and control
      cows were used to study the association between abomasal arginine and LDA, RDA or
      AV. Linear regression of arginine on LDA, RDA or AV, adjusting for age, time to
      calving, duration of illness and intraherd correlation was used for data
      analysis. Associations between arginine concentration and LDA or RDA, and between
      arginine percentage and LDA, RDA or AV were not significant. AV significantly
      increased abomasal arginine concentration. The findings do not support the
      hypothesis that arginine in abomasal fluid is related to abomasal displacement in
      dairy cows.

PMID- 9581351
TI  - The future of dentistry--the evidence revolution.
AB  - An increasing demand for evidence-based practice will transform the way we treat
      our patients in the next decade. This represents both a threat and a golden
      opportunity for GDPs. I believe that we should grasp this opportunity and in
      partnership with our academic colleagues, develop a national programme of general
      practice research.

PMID- 9581352
TI  - Complexity of malocclusions.

PMID- 9581353
TI  - Adoption of healthy habits.

PMID- 9581354
TI  - Dental health education.

PMID- 9581355
TI  - Sugar consumption.

PMID- 9581356
TI  - Dramatic condition.

PMID- 9581357
TI  - Dihydrocodeine prescription.

PMID- 9581358
TI  - Plastic trays and accurate impressions.

PMID- 9581359
TI  - A licence to learn.

PMID- 9581360
TI  - Advances in periodontal diagnosis. 6. Proteolytic and hydrolytic enzymes of
      inflammatory cell origin.
AB  - Potential proteolytic and hydrolytic enzymes of inflammatory cell origin might
      serve as biomarkers of periodontal disease activity. The role of these enzymes in
      periodontal pathology, particularly in respect of collagen and proteoglycan
      degradation, is discussed. The cellular location of these enzymes and their
      normal control mechanisms by endogenous inhibitors is described.

PMID- 9581361
TI  - Using articulators to enhance clinical practice.
AB  - This paper looks at how articulators can be of value in everyday NHS practice. A
      variation on the conventional classification of articulators is suggested with
      advice provided for the practitioner who wants to enhance his or her restorative
      work without immediately investing in high cost equipment. It is argued that
      rather than prolong chairside time, for specific types of treatment the use of an
      appropriate articulator and facebow can not only enhance the quality of the
      completed restoration, but also save on chairside time.

PMID- 9581362
TI  - The air/water syringe: a potential source of microbial contamination.

PMID- 9581363
TI  - Barriers to dental care for the elderly must be investigated and lowered.

PMID- 9581364
TI  - Workplace-based oral health awareness campaign shown to be clinically effective.

PMID- 9581366
TI  - Can a workplace preventive programme affect periodontal health?
AB  - AIM: To evaluate an oral health awareness campaign in an adult population.
      DESIGN/SETTING: Four workplaces in north-east London were selected, matched in
      two pairs and randomly allocated to test and control groups. Completion occurred
      in 1995. SUBJECTS: 98 volunteer employees in good general health. INTERVENTIONS:
      Two oral examinations were carried out, six weeks apart. The test group received
      the programme immediately after baseline examination and the controls after the
      second visit. MAIN OUTCOME MEASURES: Gingival bleeding on probing (BOP) and
      probing depths (PD) were measured on each occasion using a controlled pressure
      probe. RESULTS: The mean percentage of sites with BOP per subject reduced from
      56% to 25% in the test group, while remaining static in the control group at 46%
      to 48%. The mean percentage of sites probing 4 mm and above per subject reduced
      from 38% to 25% in the test group and from 28% to 25% in the control group. These
      differences between groups were statistically significant when submitted to
      analysis of covariance (P < 0.001). CONCLUSIONS: The study showed the clinical
      effectiveness of a workplace-based oral health awareness campaign, which is
      ideally suited to the skills and resources of the primary care dental team.

PMID- 9581365
TI  - Reported dental attendance and perceived barriers to care in frail and
      functionally dependent older adults.
AB  - OBJECTIVES: This study was designed to investigate the reported dental attendance
      and the perceived barriers to dental care for frail and functionally dependent
      older adults. DESIGN: A single centre study of a housebound group of more than 60
      years of age and their personal carers. SETTING: The study was carried out from a
      general dental practice in Ware, Hertfordshire, a market town 20 miles north of
      London. SUBJECTS AND METHODS: A group of 263 housebound adults more than 60 years
      old were identified. The subjects were living in 5 residential homes, 3 sheltered
      housing complexes and in private accommodation. The subjects and 115 of their
      personal carers were interviewed. RESULTS: 93% only attended a dentist when they
      had problems. The presence of natural teeth, residential status and age were all
      statistically significant independent explanatory variables for the time since
      the previous reported dental visit. Lack of perceived need was found to be a
      barrier to care for 86% of subjects. Cost and lack of suitable transport were
      also commonly identified. However, the true cost implication to a patient was
      poorly appreciated especially by those 34% of subjects who cited cost as a
      barrier. 52% of the whole group, rising with age to 75% of those more than 90
      years old, expressed a preference for treatment to be carried out in their own
      homes. 93% of carers had found difficulty in arranging dental care for their
      clients but the difficulties were not always the same as the subjects' perceived
      barriers. Among the carers, younger, regular dental attendees who were paid to
      care were more likely to see benefit in obtaining dental care for their clients.
      CONCLUSION: The mechanisms by which these barriers to care may be lowered should
      be investigated in order to meet the unmet need identified by this study.

PMID- 9581367
TI  - Rigidity and retention of root canal posts.
AB  - OBJECTIVE: To test the rigidity and the retention into roots of parallel root
      canal posts, one a spiral vented titanium post and the other a spiral serrated,
      hollow, stainless steel post. A serrated, stainless steel post was used as the
      control. MATERIALS AND METHODS: A three-point bending test was used to test
      rigidity. To test retention, ten posts of each type were cemented into the roots
      of extracted teeth with a resin cement and the tensile loads required to remove
      them were compared using Student's t and Mann-Whitney U tests. RESULTS: The
      serrated stainless steel posts were significantly more rigid than either of the
      other types. The titanium posts and the stainless steel hollow posts were not
      significantly different in rigidity. The serrated, stainless steel posts were
      significantly better retained than either of the other types. The titanium posts
      showed greater retention than the hollow posts. CONCLUSIONS: Within the limits of
      the study the stainless steel, serrated posts were superior to the two newer
      types in terms of rigidity and retention into roots.

PMID- 9581368
TI  - The teaching of molecular biology to undergraduate dental students within the UK.
AB  - This work was undertaken to assess the extent and nature of molecular biology
      teaching to undergraduate dental students in the UK. We surveyed the lecturers of
      those schools involved in teaching molecular biology and a questionnaire and
      covering letter were circulated to all 14 UK Dental Schools.

PMID- 9581369
TI  - [Prions and the problems they raise].
AB  - A prion is an "infectious" protein. Most probably, prions play a major role,
      direct or indirect, in the propagation of neurodegenerative diseases such as
      spongiform encephalopathies. By extension, the term prion is also used to explain
      several cases of dominant cytoplasmic heredity known in the yeast Saccharomyces
      cerevisiae. Several recent publications, briefly discussed, suggest that amyloid
      fibrils (aggregated prions) appear late in some experimental neuropathies, long
      after the disease symptoms. The present uncertainty deals with the presence or
      not of a second component besides the prion to make up the infections agent. As
      such, the prion theory raises major problems about the chemistry of protein
      folding. A major contribution in prion research is urgent and mandatory.

PMID- 9581370
TI  - BSE: can we predict the future?
AB  - Prion diseases are transmissible neurodegenerative disorders of humans and
      animals. The prion protein (PRPc) gene is expressed to some extent in many cell
      types but principally in neurons. Normal PrPc may contribute in the protection of
      neurons and are protease sensitive. Abnormal prions consist of a post
      translationally modified form of PrP, PrPsc, which is partly protease resistant.
      PrPsc is a protein with high resistance to inactivation by irradiation, heat and
      harsh chemical treatments. It is currently proposed that PrPsc is an infectious
      protein that propagates by inducing the normal PrPc to become the abnormal PrPsc.
      PrPsc cause transmissible spongiform encephalopathies (TSE), an unusual group of
      degenerative brain diseases that can be transmitted by inoculation or ingestion
      of diseased brain or other tissues. The human diseases occur in an inherited,
      acquired and sporadic forms. Transmission of prion diseases between species is
      limited by a species barrier, determined in part by the degree of sequence
      homology between the host PrPsc and inoculated PrPsc. The epidemic of bovine
      spongiform encephalopathy (BSE) in the United Kingdom is a new disease that has
      affected over 160,000 cattle and has presumably arisen from dietary exposure to
      PrPsc from sheep with scrapie. Until shown otherwise we must assume that oral
      consumption of infectious BSE protein is a new factor for Creutzfeld-Jakob (CJD)
      disease in man. This disease is a new variant of CJD (nVCJD) and has a different
      clinical picture. Early diagnostic markers to facilitate the diagnosis and screen
      blood and organ donors are not available. The control of the disease relies on
      the measures to eradicate the spread of BSE by banning the use of ruminant
      tissues in ruminant feed and slaughter and rendering procedures to ensure
      inactivation of prions of all infected animals. The control of nVCJD is based on
      reduction of exposure to BSE by banning a variety of tissues for consumption. A
      surveillance worldwide is increased for both BSE and nV-CJD and the WHO update
      regularly recommendations to limit the risk of transmitting the disease. The
      extent of the size of the nVCJD will depend on different factors among others the
      dose of infectious material, the route of infection, the genetic susceptibility
      of the person. Therefore is not possible to predict how important the disease
      will be.

PMID- 9581371
TI  - [Development and status of animal welfare legislation].
AB  - A report on the status of animal welfare legislation in the European Union as
      well as in the Federal Republic of Germany is given.

PMID- 9581372
TI  - [Animal protection in constitutional law?--On the necessity of including animal
      protection in the constitution].
AB  - The inclusion of animal protection in the constitution poses a lengthy legal
      political demand, which is again being vehemently discussed at the present time.
      Under consideration of juristic aspects, the following treatise attempts to
      clarify the legal requirements which presently exist for anchoring animal
      protection in constitutional law. It is therefore necessary in the first instance
      to explain the present situation regarding animal protection law. The legal
      situation in this respect is marked by a fundamental collision between special
      democratic rights guaranteed by the constitution on the one hand, and the norms
      of animal protection law on the other hand, which tend to restrict these rights.
      Based on concrete examples taken from court decisions, it is shown that
      constitutional vacuum surrounding a major part of animal protection law greatly
      complicates or even renders impossible the application and enforcement of the
      latter in practice. A prerequisite for a proper legal framework for animal
      protection is that the different special basic democratic rights governing animal
      use must be counterpoised by animal protection laws backed up by the
      constitution. Only by this means it is possible to prevent the ineffectiveness of
      animal protection legislative norms in the long term.

PMID- 9581373
TI  - [Patents on life? No patent on life!].
AB  - Inventions related to living material are in principle patentable as well as
      inventions in the "classical" fields of technology as long as they are new,
      industrially applicable and involve an inventive step. A patent gives to its
      owner for a limited period of time the exclusive right to prevent others from
      using his patented new technical know-how. Starting point of patent protection in
      the field of genetic engineering is a genetic information or a genetically
      induced characteristic of an organism; there is no such thing as a "Patent on
      Life". As far as inventions relate to genetically modified organisms, patents
      give to their owners no additional property rights that might exclude the
      applicability e.g. of the laws on animal protection. Intellectual property like
      any other property is subject to the limits set up by law. It is neither
      scientifically correct nor does it help in finding a solution for the conflict
      within society to shift the--undoubtedly necessary--discussion about research and
      application in the field of genetic engineering to a discussion about patent law.

PMID- 9581375
TI  - [Early castration of dogs and cats from the point of view of animal welfare].
AB  - The castration of dogs and cats is regulated in section 6 of the German Law for
      Prevention of Cruelty To Animals (Tierschutzgesetz) dated February 17, 1993.
      Gonadectomy in juvenile and prepuberal as well as in adult vertebrates is only
      permitted by law in case of a medical indication or a special using of the
      animal. On account of his special knowledge, the veterinarian is made responsible
      by law for the estimation of the indispensibility and for the performance of
      castration. As early-age castration means usually the surgical removal of healthy
      gonads from a healthy organism, it is principally forbidden by law at present.
      The bill of June 30, 1995 points to the legitimation of castration for
      contraception. This does, however, not dispense the veterinarian from deciding in
      each individual case under consideration of unwanted side effects and
      consequences that can be caused by castration and early-age castration,
      respectively.

PMID- 9581374
TI  - [The problem of seizure of animals based on sections 16 and 19 of the Animal
      Protection Act].
AB  - The present Animal Protection Act (APA) provides two options for the seizure of
      animals because of welfare reasons. The seizure of animals based on section 16 a,
      sentence 2, no. 2 APA is only possible if the later redelivery to the owner is
      intended. The definitive seizure can be based on section 19 APA when a criminal
      or disciplinary procedure is carried out. The general statutes of preventing
      danger in the federal states are not applicable.

PMID- 9581376
TI  - [Animal welfare and contraception of zoo and wild animals].
AB  - Side effects and disadvantages of contraceptive methods currently used in zoo-
      and wild animals are presented and discussed. For the preservation of wild animal
      populations in captivity, i.e. in zoos, wild animal- and national parks,
      contraception alone is not suitable without a sensible supplementary postnatal
      selection.

PMID- 9581377
TI  - [Group housing for two to eight week old fattening calves].
AB  - The effect of three different feeding techniques (electronic automated feeder,
      teat bucket and bucket with floating teat) on oral activities, skin condition,
      health and performance of 144 German Holstein group housed veal calves was
      investigated. About 21% of the observed time over 24 hours was spent on oral
      activities and only about 1% with the particularly health-relevant activities at
      prepuce, navel or scrotum. As a consequence of sucking activities at pen mates in
      most cases reddening of the skin and, with low incidence (about 7%), additional
      loss of hair could be found. Altogether about 74% of the calves were affected
      with the highest incidence in the electronic automated feeder groups. Calves of
      these groups had, moreover, higher disease incidences and a lower weight gain and
      feed conversion rate than those fed by teat bucket or by bucket with floating
      teat. Altogether results show that in terms of behaviour and health it is
      possible to keep calves at the age of two weeks in groups, even in conventional
      veal calf production, when satisfactory management is applied. The electronic
      automated feeder still needs further technical development for use with veal
      calves.

PMID- 9581378
TI  - [Mouth-nose ring to prevent cattle from sucking].
AB  - A report is given on a ring implanted in the mouth-nose-region, which prevents
      from uddersucking. Different kinds of rings are described, the implanting
      operations and the effect of the ring are explained.

PMID- 9581379
TI  - [Aspects of transport of pet animals].
AB  - The position of pet animal transport is discussed. The different transport
      situations are compared to the physical and psychological impact criteria as well
      as to the response of the animal to these impact factors. Comments on the
      transport practice of pet animals in the area of pet shops are given from the
      point of view of a veterinarian.

PMID- 9581380
TI  - [Keeping reptiles].
AB  - Keeping of reptiles in captivity is permanently increasing. As there exists such
      a great number of species of reptiles, the conditions of the natural habitat of
      the kept species have to be imitated as exactly as possible. Disorders in
      reptiles are often caused by inadequate maintainance.

PMID- 9581381
TI  - [Critical review of "Recommendations for Horse Maintenance"].
AB  - Comments are given on the present recommendations for the keeping of horses in
      stables. Proposals for an animal friendly accommodation are made including
      practical considerations.

PMID- 9581382
TI  - [Marking of horses].
AB  - The author informs on up to date identification methods of horses. The
      implantation of passive transponders is a practicable method for marking of
      horses. Because it gives less pain to horses, this method is to prefer. Stress
      inflicted on horse is minimal, it compares to a intramuscular injection. The
      reliability of the system in use has so far been very high. Members of ISO have
      voted overwhelmingly in favor of a standard for electronic identification of
      animals. From now on, countries and user organizations can make use of this
      technique to identify animals and if used can rely on the fact that their animals
      can be uniquely identified all over the world.

PMID- 9581383
TI  - [Doping of horses].
AB  - A survey is given about the situation of "doping" of horses. A definition of the
      term "doping" is delivered which is up to date and considers the matters of
      animal welfare. Existing regulations will be discussed in view of recent results
      of research. Different regulations for horses as well as humans in sports will be
      compared. Also different attempts of solutions for the regulatory body will be
      presented, which may change the regulatory significance. Finally a preview about
      actual questions related to doping is given.

PMID- 9581384
TI  - [Problems in the energy and nutritional requirements of feeding and welfare of
      food producing animals].
AB  - The efforts in optimizing feeding conditions of food producing animals in the
      past were focussed primarily on promoting performance and/or the products'
      quality (MEYER 1997). In spite of great success in this direction various risks
      occur due to the conflict between the increased requirements on the one hand and
      the species typical demands on the other (for example: need of roughage as well
      as of concentrates with high energy and nutrient density in ruminants).
      Especially in feeding high yielding dairy cows the conflict is obvious: Even in
      the case, that high amounts of concentrates are fed it becomes more and more
      difficult to meet the energy requirement when the milk yield exceeds 40 kg milk
      per day (FLACHOWSKY a. LEBZIEN 1997). A negative energy balance is accompanied by
      a forced predisposition for ketosis and infertility (KRUIP 1996). Insufficient
      proportions of roughage in those rations predispose the animals for rumen
      acidosis and associated problems (health of claws etc.) as well as for
      displacement of abomasum. Thereby in feeding high yielding dairy cows there is
      only the choice between different risks due to the fact that the feed intake
      capacity did not increase to the same extent as the milk production did. In
      fattening calves the use of roughage (in Germany required by law) is on debate in
      this direction (necessary to avoid disturbances in the behaviour). Further
      problems in feeding animals according to their species typical demands are
      related to the established conditions of housing, feeding and water supply (risks
      of mechanization and automatization due to potential disfunction). The generally
      increased feeding intensity results--for example in poultry--in a higher
      frequency of skeleton diseases; the more and more specialized pig production
      (separate units for piglet production, rearing units, fattening units) is
      accompanied by increased changes in diets and techniques of feed and water
      supply, to that the animals have to be accustomed, too. The science of animal
      nutrition gets more and more involved in questions on the species depending
      requirements that guarantee a physiological development of the animal, health and
      normal behaviour. There is an increased need to create and evaluate parameters
      that can be used for characterization animals' well-being related to different
      feeding strategies. Without any doubts it is a special task to veterinary
      nutritionists to point out risks, problems, conflicting aims when the feeding
      intensity is forced continuously. The slogan "back to nature" is too simple and
      does not correspond to the complexity of efforts which are suitable and necessary
      to meet animals' energy and nutrient requirements as well as demands of animals'
      welfare. Eventually it is helpful to remember sometimes the limits set up by the
      biology and physiology when feeding intensity or techniques are on debate.

PMID- 9581385
TI  - [Review of nutritional conditions of horses and cattle as a tool in veterinary
      services animal welfare procedures].
AB  - The control of husbandry by veterinarians with the prospect of animal welfare
      demands a valuation of the nutritional status of farm animals. The situation of
      main importance is a suspected undernutrition. A prolonged failure in nutrient
      and energy supply results in mobilisation of body fat as well as body protein.
      Especially the protein depletion includes a loss of capacity of several essential
      functions, e.g. of the immune system or the respiratory tract. Undernutrition is
      often classified as stress, but the typical parameters for stress related
      reactions offer no sufficient information to evaluate a case of undernutrition. A
      useful tool to justify the nutritional status of an animal is the amount of body
      fat by sonographic measurements. Processes related to reproduction are rather
      sensible to a reduction of body fat; although they are less expensive by energy
      point of view compared to exercise or milk production. Measuring body fat offers
      the opportunity to describe the degree of undernutrition and to appreciate, if a
      malnourished animal is damaged accordingly the definitions of animal welfare.
      However, the equipment and the experience to use sonographic methods is often not
      available for veterinarians, who are responsible in official control of
      husbandry. But the visual and manual procedures to proof defined areas, mainly
      related to back fat thickness, well known as the body condition scoring,
      alternatively can be used. The body condition score systems, as defined for cows,
      sheep and horses, are proofed by different experiments with regard to accuracy
      and reproducibility. They completely cover the demand in precision to evaluate
      body fat and in consequence the nutritional status of an animal.

PMID- 9581386
TI  - [Keeping, transport and racing of sled dogs].
AB  - An introduction of the practice of sled dog racing in Germany is given. Reference
      is made to the origin (Alaska, Siberia, special breeds) of the dogs, the keeping
      systems, the preparation for racing, transport and rules of racing, either on
      snow or when snow is lacking on bare ground. In some countries tethering of dogs
      is still allowed. The keeping in groups in kennels suits the animals, tieing is
      easier for man. There are sprint races (4-18 km), middle distances (40-450 km)
      and long distance races (> 500 kg-1000 miles). Below -25 degrees C no sprint
      races are performed. Above +15 degrees C ambient temperature all races are
      stopped (hyperthermia). The close control of the kennels and the permanent
      control of the health of the dogs before and when racing by veterinarians is
      asked for by organisations, owners and performers. The veterinarian decides on
      each dog individually whether it is fit for racing or not. There exists an
      International Association of Veterinarians for sled dogs (ISDVMA).

PMID- 9581388
TI  - Footplate otosclerosis and tympanic membrane perforation.

PMID- 9581387
TI  - [Sled dog racing and animal welfare aspects].
AB  - Transport, housing and the dimensions of strain during training and race are
      important aspects of animal welfare. The race veterinarian has a great
      responsibility. He is responsible for the treatment of injured dogs and he has to
      give advice on all medical and animal welfare questions. The presence of the
      veterinarian during the entire race is very important. These veterinarians should
      have special knowledge of small animals and of sled dogs in particular. There
      should be health checks of sled dogs before and after racing similar to horse
      sport tournaments.

PMID- 9581389
TI  - Vocal fold mass and scar.

PMID- 9581390
TI  - Esophageal stethoscope mimicking an antrochoanal polyp.

PMID- 9581391
TI  - Waardenburg syndrome.

PMID- 9581392
TI  - The abnormal internal acoustic canal.

PMID- 9581393
TI  - Effect of corrective make-up training on patients with facial nerve paralysis.
AB  - Two women who suffered from facial nerve paralysis following surgical resection
      of a posterior fossa tumor were instructed by an expert beautician in the
      application of make-up to correct their facial imbalances. The results of a
      personality assessment administered before and after instruction showed positive
      changes including reductions in depression and feelings of inferiority.
      Postoperative restoration of normal facial appearance and recovery of physiologic
      function are related and important concerns to patients. It is noteworthy that
      daily use of simple low-cost make-up techniques can significantly reduce the
      "psychological load" of patients with facial paralysis during the recovery
      period.

PMID- 9581394
TI  - Mammalian auditory hair cell regeneration/repair and protection: a review and
      future directions.
AB  - Regeneration/repair and protection of auditory hair cells and auditory neurons is
      an exciting, rapidly evolving field. Simultaneous developments in the fields of
      otobiology and surgical otology have led to new and exciting possibilities in
      inner ear medicine and surgery; specifically, the treatment or prevention of a
      variety of types of hearing losses in the foreseeable future. Sensorineural
      hearing loss in humans is commonly associated with a loss of auditory hair cells.
      It has been generally accepted that hearing loss resulting from hair cell damage
      is irreversible because the human ear has been considered to be incapable of
      regenerating or repairing these sensory elements following severe injury. An
      organ of Corti explant study has shown that it is possible to initiate the
      regeneration/repair of mammalian hair cells. In this study, ototoxin-damaged
      organ of Corti explants from juvenile rats were treated with a combination of
      retinoic acid (10-8M) and fetal calf serum (10%). TGF-alpha has been identified
      as a growth factor capable of evoking auditory hair cell regeneration/repair in
      ototoxin-damaged organ of Corti explants. Preliminary in vitro experiments with
      juvenile rat organ of Corti explants and in vivo studies in the cochleae of adult
      guinea pigs indicate that pretreatment followed by continuous treatment of the
      inner ear with a combination of retinoic acid and TGF-alpha can protect the
      auditory hair cells from the ototoxic effects of aminoglycosides. Because the
      integrity of spiral ganglion neurons is also essential for normal auditory
      function, there is a parallel series of in vitro and in vivo studies of the
      effects of neurotrophic factors on the survival of auditory neurons and the
      regeneration of injured neuronal processes. Clinical studies have demonstrated
      that it is now possible to perform surgeries on the inner ear, i.e., partial or
      total labyrinthectomies, and maintain hearing. The field of cochlear implantation
      has also provided insights into both the short- and long-term effects of cochlear
      fenestration on inner ear function. Administration of growth factors to the inner
      ears of animals is now possible with the use of implanted catheters and miniature
      infusion pumps. These advances suggest that localized application of drugs to the
      human inner ear may be feasible. The aim of this paper has been to provide an
      overview of advances in the study of the biology of auditory hair cells and
      auditory neurons, as well as recent relevant surgical advances. Taken together,
      these advances in otobiology and surgery will, in the future, be combined to
      devise new and innovative treatments for inner ear disorders.

PMID- 9581395
TI  - Nasal flow volume loop as measurement of response to intranasal drug therapy.

PMID- 9581397
TI  - Cochlear implantation in sudden bilateral sensorineural hearing loss.
AB  - Although 1-4% of all cases of sudden sensorineural hearing loss (SSHL) are
      bilateral, all such patients reported to date have experienced significant
      recovery of hearing in at least one ear. We report a case of profound, bilateral
      idiopathic SSHL without recovery which was treated with cochlear implantation;
      the first such report to our knowledge. The patient achieved open-set spondee
      recognition. Individuals with sudden bilateral hearing loss in whom treatable
      causes have been eliminated may benefit from cochlear implantation.

PMID- 9581396
TI  - Analysis of patients with persistent dizziness after vestibular nerve section.
AB  - Vestibular neurectomy can be an effective operation for the control of persistent
      dizziness refractory to medical treatment or even endolymphatic sac surgery. Past
      studies have reported favorable results, creating an almost deceptive impression
      of the procedure's success rate. However, not all patients will respond
      favorably. Some will continue to have significant postoperative disequilibrium
      and, worse yet, persistent vertigo. To analyze the reasons for continued
      problems, 142 patients undergoing various surgical approaches employed to divide
      the vestibular nerve (retrolabyrinthine, middle fossa, retrosigmoid and
      translabyrinthine) were retrospectively, reviewed. Twenty-nine patients (20%)
      continued to have significant dizziness despite vestibular neurectomy. The
      reasons for failure were incomplete vestibular nerve section, poor central
      nervous system compensation, new vestibular disease in the opposite ear,
      obstructive anatomy, the presence of other central nervous system diseases, and
      unknown causes. This paper will detail the advantages and disadvantages of
      various vestibular neurectomy approaches and will present recommendations for
      further treatment of this difficult-to-manage group of patients.

PMID- 9581398
TI  - Inferior turbinate reduction surgery in children.
AB  - We assessed the effectiveness and safety of surgical reduction of the inferior
      turbinate in 64 children, ages three to 15 years, who were operated on between
      January 1985 and November 1995. All patients/parents were interviewed and
      assessed by means of a questionnaire one to 10 years postoperatively. All
      patients had follow-up and were evaluated clinically at one and two weeks
      postoperatively. Long-term follow-up visits occurred at six, 12 and 24 months.
      Eighty-nine percent of the children/parents reported a sustained improvement in
      their nasal airways. No cases of serious postoperative hemorrhage, excessive
      dryness nor long-term crusting of the nose were observed or reported. We conclude
      that in the treatment of children with severe nasal obstruction, surgical
      reduction of the inferior turbinate is a safe and effective operation, alone or
      in combination with other airway procedures, and may increase the effectiveness
      of subsequent medical management.

PMID- 9581399
TI  - Lingual osseous choristoma: a study of eight cases and review of the literature.
AB  - A choristoma is a tumor-like mass of normal tissue in an "abnormal" location.
      Lingual osseous choristoma, previously known as osteoma of the tongue, is a rare
      entity: we found documentation of eight cases at our center during the 10-year
      period between 1987 and 1996. These cases were analyzed along with 50 others
      reported in the English language literature between 1913 and 1996. Lingual
      osseous choristoma frequently occurs during the third and fourth decades of life,
      and predominantly affects women (81%). Most of the osseous choristomas in our
      review were located in the posterior third of the tongue, primarily at or close
      to the foramen cecum or circumvallate papillae (87.9%). While 39.7% of the
      patients were asymptomatic, the remaining patients complained of symptoms
      including a lump in the throat (25.8%), dysphagia (6.9%), gagging (5.1%), nausea
      (3.4%) and irritation (3.4%). Treatment of lingual osseous choristoma consists of
      simple excision. The tumor's origin has been discussed elsewhere.

PMID- 9581400
TI  - Pre- and postoperative imaging analysis for frontal sinus disease following
      conservative partial middle turbinate resection.
AB  - The prudence of partial or complete middle turbinate resection during endoscopic
      sinus surgery (ESS) is controversial. The greatest concern regarding partial
      resection relates to the effect on the frontal recess and the development of
      frontal sinus disease. The purpose of this study was to radiographically evaluate
      the frontal sinus in patients who had undergone ESS with partial conservative
      middle turbinate resection. We reviewed the charts and operative records from 195
      consecutive cases of ESS performed by a single surgeon (JFB) over a two-year
      period. Thirty-three of 117 patients who had undergone ESS with conservative
      partial middle turbinate resection without frontal recess exploration agreed to
      return for magnetic resonance imaging (MRI) of their sinuses. The preoperative
      computed tomography (CT) scans and postoperative MR images were reviewed and
      graded (1-3) by a single neuroradiologist. Significant frontal sinus disease
      (grades 2 and 3) was seen in 15 of 52 sides preoperatively (29%), and in 14 sides
      postoperatively (27%). During the postoperative MRI studies, only six frontal
      sinus sides demonstrated minimal mucosal thickening (grade 1) which had not been
      apparent on preoperative CT. This radiographic analysis suggests that
      conservative partial middle turbinate resection during ESS does not adversely
      affect the frontal sinus. We believe that the surgical technique employed when
      resecting the middle turbinate, and the avoidance of unnecessary dissection in
      the recess are both important factors in preventing the development of frontal
      sinus disease following ESS.

PMID- 9581401
TI  - Generalizations regarding the process and phenomenon of osseointegration. Part
      II. In vitro studies.
AB  - In this review, the appropriate use of cell culture to evaluate substrate effects
      on osteoblast behavior during the process of osseointegration has been considered
      in the context of existing reports. The interactions of osteoblasts with
      different substrates can be measured in terms of cytotoxicity, attachment,
      proliferation, and differentiation. The osteoblast culture systems that produce
      an osteoblast matrix opposing implant material substrates provide one model for
      evaluating the implant-bone interface. Alterations in osteoblast behavior at
      different culture substrates may reflect clinical determinants of bone formation
      at these substrates in vivo; however, cell responses in vitro have not been
      compared or correlated with in vivo outcomes. Legitimate interpretations of in
      vitro experiments are discussed in terms of practical, technical, and biologic
      limitations presented by the cell culture approach. Cell culture provides access
      to molecular and cellular information that fosters nanostructural engineering
      approaches to implant design and significant hypotheses to be tested in vivo. In
      this way, cell culture offers unique insights into the process and phenomenon of
      osseointegration.

PMID- 9581402
TI  - A review of survival rates for implants placed in grafted maxillary sinuses using
      meta-analysis.
AB  - A variety of materials and procedures are used to create adequate bone volume in
      the maxillary sinus for placement of endosseous implants in the posterior
      atrophic maxilla. This review used the structured method of meta-analysis to
      evaluate the survival of the implants placed into various materials that have
      been used in the maxillary sinus with the sinus lift procedure. A MEDLINE
      computer search of the English literature yielded 28 studies that reported using
      the maxillary sinus augmentation procedure to increase bone volume for placement
      of endosseous implants; only 10 of these met the inclusion criteria for meta
      analysis. Data regarding immediate or delayed placement of implants were combined
      to simplify analysis. Implant survival was 90% for autogenous bone (484 implants
      in 130 patients followed for 6 to 60 months), 94% for the combination of
      hydroxyapatite (HA) and autogenous bone (363 implants in 104 patients followed
      for 18 months), 98% for the combination of demineralized freeze-dried bone (DFDB)
      and HA (215 implants in 50 patients followed for 7 to 60 months), and 87% for HA
      alone (30 implants in 11 patients followed for 18 months). The results for
      autogenous bone were based on six reports, for the combination of autogenous bone
      and HA on three reports, and for DFDB/HA and HA alone on one study each. The
      results of single studies cannot be weighted as heavily as the results combining
      several studies; however, the analysis of these studies suggests that implant
      survival rates were similar for autogenous bone, HA/autogenous bone mix, HA/DFDB,
      and HA alone.

PMID- 9581404
TI  - Description and evaluation of a simplified method to achieve passive fit between
      cast titanium frameworks and implants.
AB  - Because osseointegrated implants have no resilience in bone, passive fit between
      dental implants and prosthetic superstructures has been identified, both from
      biologic and mechanical perspectives, as a potential discriminating prognostic
      factor. Distortion of the metal framework during the casting procedure has been
      cited as a main cause of misfit. The objectives of the present article were to
      describe a recently presented method (Cresco Ti Precision method) intended to
      correct for distortion in cast titanium frameworks, and to elucidate and evaluate
      the method by photoelastic and strain gauge techniques. The method appears to be
      an efficient and accurate procedure for correcting for distortion in cast
      titanium frameworks.

PMID- 9581403
TI  - Effects of steroid-induced osteoporosis on osseointegration of titanium implants.
AB  - The purpose of this study was to clarify the effects of steroid administration on
      the osseointegration of pure titanium implants. Twelve female New Zealand white
      rabbits, 8 weeks of age, were divided into two groups: a prednisolone-treated
      group (Group P) and a control group (Group C). In each rabbit, two implants were
      placed into the mandible and two into the tibial metaphyses with bone tapping.
      The six steroid-treated rabbits received three courses of 4 days of prednisolone
      injections (10 mg/kg per day) before implant placement, 1 month and 2 months
      after implant placement. The six control rabbits received no administration of
      prednisolone. Three months after implant placement, all rabbits were sacrificed.
      Bone density of the femur and removal torque of the implants placed in the tibia
      were significantly lower in Group P than in Group C. In addition, there were
      significant correlations between the bone density of the femur and the removal
      torque of the implants placed in the tibia. There was no significant difference
      in removal torque of the implants placed in the mandible between Group P and
      Group C, and there was no significant correlation between the bone density of the
      femur and the removal torque of the implants placed in the mandible. These
      results suggest that steroid administration could have less effect on the
      osseointegration of titanium implants in the mandible than in the skeletal bone.

PMID- 9581406
TI  - Treatment outcomes of patients with implant-supported fixed partial prostheses.
AB  - Implant and prosthesis success for 77 partially edentulous patients, provided
      with 97 fixed prostheses, supported by 230 Branemark implants, in place for up to
      12 years (mean 5.41 years), were documented in this study. Implant losses per
      location mirrored their placement, with no difference between zones I and II or
      between the maxilla and mandible. The implant success rate was 94%, and
      continuous prosthesis stability was 97%. These results indicate that the
      Branemark implant-supported fixed partial prosthesis is a highly efficacious
      treatment.

PMID- 9581405
TI  - Dosimetric measurement of scattered radiation from dental implants in simulated
      head and neck radiotherapy.
AB  - The purpose of this study was to examine the dose enhancement at bone-implant
      interfaces from scattered radiation during simulated head and neck radiotherapy.
      Three cylindric implant systems with different compositions (pure titanium,
      titanium-aluminum-vanadium alloy, titanium coated with hydroxyapatite) and a high
      gold content transmandibular implant system (gold-copper-silver alloy) were
      studied. Extruded lithium fluoride single crystal chips were used as
      thermoluminescent material to measure radiation dose enhancement at 0, 1, and 2
      mm from the bone-implant interface. The relative doses in buccal, lingual,
      mesial, and distal directions were also recorded and compared. The results
      indicated that the highest dose enhancement occurred at a distance of 0 mm from
      the bone-implant interface for all the implant systems studied. The
      transmandibular implants had higher scattered radiation than other groups at 0 mm
      and at 1 mm from the bone-implant interface. There was no significant difference
      of dose enhancement between buccal, lingual, mesial, and distal directions.
      Titanium implants coated with hydroxyapatite demonstrated the best results under
      the simulated irradiation.

PMID- 9581408
TI  - Localized management of sinus floor with simultaneous implant placement: a
      clinical report.
AB  - Localized management of sinus floor (LMSF) achieves implant placement and sinus
      lifting simultaneously. LMSF is a further application of the principles of the
      edentulous ridge expansion (ERE) technique. It comprises the dissection of a
      partial-thickness flap, the buccal expansion of the residual alveolar bone, and
      the fracture and elevation of the sinus floor with simultaneous implant
      placement. Three hundred three patients were treated with 499 implants placed
      using the LMSF between April 1988 and December 1993. The selected patients, who
      showed no signs of sinus pathology, exhibited insufficient vertical alveolar bone
      dimensions for the placement of dental implants with the traditional technique.
      The minimal residual alveolar bone height was between 5 and 7 mm. Based on the
      criteria established by Albrektsson and his coworkers in 1986, the success rate
      of the 499 implants placed with the LMSF was 97.5%.

PMID- 9581407
TI  - A 5-year multicenter study on implant-supported single crown restorations.
AB  - In this multicenter prospective study, the results achieved with the use of
      Branemark implants for single tooth replacement were evaluated. The overall
      cumulative success rate was 95.9% for implants and 91.1% for crowns. Two of the
      99 implants placed had to be removed before the prosthodontic stage of treatment;
      thus, 97 were restored with CeraOne crowns. Seventy-seven implants were evaluated
      radiographically at the 1-year follow-up, 57 at 3 years, and 47 at 5 years. Mean
      marginal bone resorption was well within the limits set by Albrektsson et al in
      1986. The status of the soft tissue around crowns and adjacent teeth remained
      stable over the evaluation period. The gold abutment screw in the CeraOne system
      seems to have eliminated the problem of loosening abutment screws in single tooth
      replacements. The results suggest that the Branemark system can be safely used
      for tissue-integrated replacement of single teeth.

PMID- 9581409
TI  - Natural tooth intrusion phenomenon with implants: a survey.
AB  - A common assumption when planning for treatment for a fixed partial denture
      potentially involving an osseointegrated implant is to avoid connection between
      the implant and natural tooth abutment because of the differences in mobility and
      potential long-term effects. A large population was surveyed to measure the
      incidence of natural tooth intrusion in implant-assisted fixed partial dentures
      (IAFPD) and to try to identify a correlation between type of implant and/or type
      of connector. Natural tooth intrusion occurred in 3.5% of the patient population
      specifically treated with IAFPD. No correlation could be made between incidence
      of intrusion and the type of implant or type of connector used.

PMID- 9581410
TI  - In vivo horizontal bending moments on implants.
AB  - To date, transverse and vertical forces applied eccentrically to the axis of
      dental implants in the molar area during oral function have not been quantified.
      A specially designed load cell placed directly in the implant allowed for
      measurements of bending moments. Results of both load directions were compared to
      each other and to the loads applied vertically along the implant axis. The stress
      in the bone-implant interface area caused by these three different types of loads
      was calculated by finite element analysis. The transverse loads during chewing
      resulted in the highest bending moments (170 Nmm mean maximum) and the highest
      stress in the bone (sigma max approximately 6.2 MPa) at the crest to the buccal
      side. Mesial implant moment was significantly less (52 Nmm mean maximum moment;
      sigma max approximately 1.3 MPa). Clenching in centric occlusion caused a bending
      moment either to the lingual or to the buccal side, depending on the occlusal
      contour (140 Nmm maximum).

PMID- 9581411
TI  - Console abutment loading in craniofacial osseointegration.
AB  - Retention of implant-supported facial prostheses presents challenges in design
      that may lead to use of freestanding abutments. This is particularly so in the
      midface and orbit. Individual implant success rates are lower in these regions,
      and bone remodeling capacity may be compromised by combined modality cancer
      therapy. The present study was undertaken to determine the variations in load
      delivery so as to compare the use of long cantilevers and offset abutments with
      freestanding axially loaded abutments. The study revealed not only that the loads
      delivered are not trivial, but also that the highest loads generated are
      frequently delivered at the cervix of the implant. The long cantilevers produced
      the highest laterally acting cervical loads, whereas the 30-degree and 60-degree
      Console abutments delivered the highest laterally acting cervical loads of all
      the Console abutments. The potential of long cantilevers and offset abutments to
      deliver significant loads should be considered when designing retention for a
      facial prosthesis.

PMID- 9581412
TI  - Implant-supported overdentures: a longitudinal prospective study.
AB  - The aim of this study was to evaluate the clinical function and long-term
      prognosis of overdentures retained by a small number of implants in the maxilla
      and mandible using one of two different attachment systems. Included in the study
      were all patients referred to specialty clinics in Jonkoping and Linkoping,
      Sweden, during the treatment period who needed an overdenture and could be
      provided with a minimum number of two bilaterally-placed implants. Excluded were
      patients with bone-grafted jaws, irradiated cancer patients, heavy bruxers, and
      patients who had lost a fixed prosthesis because of implant losses. The patients
      were randomly assigned to receive one retentive system, either a round 2-mm
      diameter bar with clips or ball attachments (Nobel Biocare). Eighteen
      overdentures were placed in maxillae and 32 in mandibles, supported by a total of
      115 Branemark implants. Of the implants placed, 86.1% were continuously
      osseointegrated. The cumulative implant survival rates after 7 years of loading
      were 75.4% in the maxillae and 100% in the mandibles. There was no difference in
      implant survival rate between the attachment systems. Patients with implant
      losses were characterized by severely resorbed maxillary ridges and inferior bone
      quality, together with unfavorable loading circumstances such as short implants
      combined with long leverages. Complications and prosthetic adjustments were
      mostly resolved early and easily.

PMID- 9581413
TI  - Use of the Endopore dental implant to restore single teeth in the maxilla:
      protocol and early results.
AB  - This report outlines the experimental, surgical, and prosthodontic protocols for
      a prospective clinical trial using the Endopore dental implant to replace single
      maxillary teeth. Twenty patients (10 male, 10 female) ranging in age from 30 to
      60 years each received one implant (mean length 10.1 mm), which, after an initial
      healing period of 4 months, was restored with a single crown. Records collected
      included radiographs, Periotest mobility measurements, supragingival Plaque
      Index, and an assessment of peri-implant soft tissue health using pocket probing
      depths, sulcular bleeding following probing, and probing attachment levels.
      Radiographs were exposed at predetermined intervals following crown placement (1
      and 6 months, and then yearly) in a standardized procedure using a specialized
      filmholder that attaches to each implant after removal of the crown. At the time
      of this preliminary report, all of the 20 implants placed had been uncovered and
      were in function; 16 of the implants had been in function for 6 months or more,
      14 had passed 1 year of function, and 3 had passed the 2-year function point.
      There have been no failures to date.

PMID- 9581414
TI  - Clinical and histologic features of a nonaxial load on the osseointegration of a
      posterior mandibular implant: report of a case.
AB  - The authors report on the clinical and histologic features of a single implant
      replacing a mandibular molar, which fractured after a 1-year loading period.
      Because of anatomic factors, the implant had been placed in an angulated
      position. The histologic examination showed a very high percentage of bone
      implant contact. The bone located at the interface with the implant was mature,
      compact, and had few marrow spaces. No resorption areas were present, and no
      connective tissue was seen at the interface. Most likely, the lateral nonaxial
      forces exerted on the implant created very high bending moments. These forces
      produced a fracture of the implant, although no loss of osseointegration was
      observed at the interface.

PMID- 9581415
TI  - The 2nd Asian-Pacific Congress of Epidemiology jointly with the 8th Scientific
      Meeting of Japan Epidemiological Association. Tokyo, Japan, 28-30 January 1998.
      Abstracts.

PMID- 9581416
TI  - Early intervention programs.

PMID- 9581417
TI  - Prevalence and correlates of obesity in preschool children.
AB  - Obesity, a common nutritional disorder in childhood, is a complex problem that is
      poorly understood. The purpose of this study was to identify the prevalence of
      obesity in preschool children, and to examine the relationships between obesity
      and gender, race, socioeconomic status, and health problems. Data were collected
      from 309 charts of children enrolled in a Head Start program. Ninety-nine (32%)
      of the children were obese. Obese children had significantly higher blood
      pressure readings than those who were not obese. This study represents a
      beginning effort to learn more about the prevalence of, and factors associated
      with, obesity in preschoolers.

PMID- 9581418
TI  - Risk-taking in preschool children.
AB  - This study was designed to characterize preschool-age children who engage in
      daring, risk-taking behaviors. Seventy-four children (39 males, 35 females) and
      their mothers from a wide range of socioeconomic strata participated. Children
      who described themselves as high in risk-taking were generally males, had higher
      accident and injury rates, and had parents whose assessments of their children's
      risk-taking activities were congruent with their own. Contrary to our
      expectations, however, risk-taking children did not appear to be more than
      ordinarily impulsive, which suggests that risk-taking is engaged in
      contemplatively (i.e., with some caution) by some youngsters and need not result
      in serious mishaps. Cognitive ability was found to be a codependent predictor of
      risk-taking for boys. Parents and clinicians will find it useful to know that
      risk-taking is a multidimensional phenomenon, not a unitary behavior or
      personality trait and that the Injury Behavior Checklist would be a valuable tool
      for screening selected populations.

PMID- 9581419
TI  - The new varicella vaccine: efficacy, safety, and administration.
AB  - Since the FDA has given approval for the manufacture of a varicella vaccine
      (Varivax), nurses are beginning to administer the vaccine to children. Over
      11,000 healthy and immunocompromised children have been immunized since 1979.
      Varivax has been found to be 95% to 100% effective in conferring immunity for at
      least 10 years, and it appears to be a safe vaccine. This article presents a
      review of the research literature on clinical trials of Varivax, and the risks,
      benefits, and projected cost of the vaccine. Precautions, contraindications, and
      guidelines for administration are tabled and discussed in a sample case using the
      Health Belief Model as a theoretical framework. The article includes a discussion
      of areas for further research and implications for nursing.

PMID- 9581420
TI  - Family dynamics in families with very low birth weight and full-term infants: a
      pilot study.
AB  - The purpose of this pilot study was to determine differences in family health
      across six dimensions of functioning between families with a very low birth
      weight infant (VLBW) and families with a full-term infant. An epidemiologic model
      and Barnhill's (1979) system theory of healthy family dynamics provided the
      organizing framework for the study. Sixteen families with a VLBW infant and 25
      families with a full-term infant were assessed for differences in family health
      across Barnhill's six dimensions. Independent t-tests showed no significant
      differences on the five dimensions of infant behavioral style. While a 2 x 3
      MANOVA showed no significant differences on any of the measures by family, the
      Turkey HSD post hoc tests for main effect found significant differences related
      to the mothers' position within the family, Specifically, the position the mother
      maintains in the family significantly contributes to certain dimensions of family
      health.

PMID- 9581421
TI  - Foster parents of cocaine-exposed infants.
AB  - The purpose of this study was to describe the experience of foster parents of
      cocaine-exposed infants. A qualitative approach was selected because of the
      paucity of knowledge on the topic. Results showed foster parents observed
      alterations in physiological and behavioral health, developmental problems, and
      variability among infants related to these problems. Foster parents were
      concerned about the future development of infants. They felt the experience of
      living with a cocaine-exposed infant gave them a unique view of the effects of
      exposure. Parents found difficulties obtaining social services. Foster parents
      reported problems with access to and appropriateness of health care and
      identified difficulties arising from community reaction to foster parenting.
      Recommendations focused on the need for more research on social, developmental,
      and behavioral effects of cocaine exposure and increased attention to the needs
      and concerns of foster parents.

PMID- 9581422
TI  - Videotaped assessment of parenting practices: a preliminary report.
AB  - Assessment of parenting skills was based upon a standardized videotape of
      vignettes of parents reading a magazine while their children were playing,
      playing with their children, or trying to get them to clean up. Parents who
      viewed this videotape came from 40, 2-parent families referred to an outpatient
      clinic for behavior problems (Behavior Problem group) or 20 nonreferred 2-parent
      families (Nonclinic group). They were compared on the degree to which they
      selected: (1) positive responses to children's prosocial behavior (praise), (2)
      ignoring children's inappropriate behavior (ignore), and (3) punishing children's
      aversive behavior (punish). The Nonclinic group was more accurate than the
      Behavior Problem Group and mothers were more accurate than fathers in their
      selection of praise to children's prosocial behavior. Nonclinic mothers were more
      accurate than all other combinations of Group and Parent Sex in their selection
      of ignore for children's inappropriate behavior. Sensitivity calculations
      suggested that this instrument could potentially be useful as a screening tool in
      clinical pediatric practice and early intervention. Implications for nursing
      research and practice were discussed.

PMID- 9581423
TI  - Changes in transcultural nursing and its influence on the growth of Australian
      aboriginal children.
AB  - The health of Australian Aboriginal people is reportedly poor. This report
      discusses how nurses, over a generation, have helped improve the health of
      children at an Aboriginal community in Queensland, Australia. By delivering
      health services using the principles of transcultural nursing, the nurses were
      able to deliver culturally congruent nursing care. This empowered the families to
      become active seekers of health care, rather than passive recipients.

PMID- 9581424
TI  - Child abuse and neglect: (Part I) A status report.

PMID- 9581425
TI  - Rapid strep tests in the pediatric clinical setting.

PMID- 9581426
TI  - Lean and mean: the quality of care in the era of managed care.
AB  - This paper reviews the genesis of managed care and the reasons for its rapid
      growth. The effects of the differing incentives of traditional and managed-care
      plans on quality of care are described. There is an urgent need for federal,
      state and local health departments to monitor and regulate the quantity and
      quality of health care provided by all types of insurance plans. The elements of
      such a program are outlined, and the need for adequate funding as well as
      political and technical leadership is emphasized. This should become a major
      priority issue for the public health movement in the United States.

PMID- 9581427
TI  - Epidemiology and health policy in the Americas: meeting the neoliberal challenge.
AB  - This paper analyses the anti-health policies and programs that are being pursued
      by neoliberal governments on a global scale, and that are being sold to the
      public by labeling them as "health reforms." The role of epidemiologists in this
      situation is to strengthen opposition to these anti-health reforms by documenting
      their effects on preventive and therapeutic health services and on the health
      status of the population. Major difficulties in this regard are discussed. There
      is a great need for epidemiologists to move boldly forward to attack the major
      diseases that afflict the Americas today. Two examples of high-priority programs
      are discussed: the achievement of safe water supplies by newly developed, low
      cost community-based initiatives, and the long over-due organization of effective
      campaigns against cardiovascular disease. The establishment of specific, concrete
      Health Objectives at all levels of government--national, state/provincial, and
      local--must become the central focus of public health policy and action
      throughout the Americas. Epidemiologists are urged to take leadership in
      advocating and achieving this fundamentally epidemiologic approach.

PMID- 9581428
TI  - The public health versus clinical approaches to maternity services: the emperor
      has no clothes.
AB  - This paper explores the conflict between practice based on science, or based on
      peers, and between the recommendations of public health agencies and the
      recommendations of organizations of clinicians, with specific reference to
      maternity services. The WHO European Regional Office, as a public health agency,
      has been bringing to the attention of the public and of governments two serious
      problems brought about by the present hegemony of the clinical approach: (1) The
      reliance on standards of practice rather than scientific evidence, and (2) Having
      doctors decide health policy, leading to the failure to honour the self
      determination of the individual and family and basic human reproductive rights.

PMID- 9581429
TI  - Preemption or prevention?: lessons from efforts to control firearms, alcohol, and
      tobacco.
AB  - The judicial doctrine of preemption allows federal or state governments to
      restrict the ability of state or local governments, respectively, to regulate in
      a given area. Industries whose products create substantial public health risks
      have begun to promote preemptive legislation which prevents the lower levels of
      government from adopting strong public health protections. This article discusses
      the implications of preemptive legislation concerning three of the most harmful
      products available in America: tobacco, firearms and alcohol. These examples
      illustrate the potential danger that preemptive legislation poses to efforts to
      prevent illness, injury and death caused by these products.

PMID- 9581430
TI  - Effectiveness and role of driver education and training in a graduated licensing
      system.
AB  - Formal driver education/training programs exist in almost all jurisdictions
      around the world. They are generally accepted as an efficient and effective means
      for learning to drive, and, more importantly, for learning to drive safely,
      although empirical evidence for safety benefits is lacking. Recently, there has
      been a heightened interest in driver education/training, largely as a result of
      the adoption of graduated licensing in a few jurisdictions in North America and
      elsewhere. These jurisdictions have effectively elevated the status of driver
      education/training by integrating it into the licensing system. Implicitly, this
      suggests that driver education provides safety benefits. This article provides a
      contemporary review of the value of driver education/training, particularly in
      relation to new licensing systems such as graduated ones. The article examines
      the safety benefits of driver education/training and considers the merits of
      integrating driver education/training programs with new approaches to the
      licensing of young drivers.

PMID- 9581431
TI  - Alcohol and the U.S.-Canada border: trade disputes and border traffic problems.
AB  - The public health interest in trade and in cross-border traffic of alcoholic
      beverages is considered in general terms. Within this framework, three specific
      issues in U.S.-Canada trade and borders are discussed: cross-border drinking and
      driving in both directions, particularly by youth; smuggling from the U.S. to
      Canada; and the "beer wars" and other U.S.-Canada trade disputes involving
      alcoholic beverages. While problems can be alleviated on each of these fronts, it
      is concluded that an important step internationally would be to establish that,
      because of the problems they entail, alcoholic beverages should be exempt from
      trade agreements, or else provision should be made for the public health interest
      to be represented in negotiations and dispute resolution involving alcoholic
      beverage controls.

PMID- 9581432
TI  - Body mass and social class: a comparison of Finland and Sweden in the 1990s.
AB  - High physical weight affects public health as well as people's social relations.
      This study seeks to examine the distribution of physical weight across the social
      structure in Finland and Sweden in the early 1990s. We compare physical weight,
      classified by overweight and obesity, 1) between men and women, 2) between
      different age groups, and 3) between social classes in these two countries.
      Comparable interview surveys were conducted in Finland 1994 (N = 8,650, response
      rate 73%) and in Sweden 1991 (N = 5,306, response rate 79%). Physical weight,
      overweight and obesity of populations are described in terms of body mass index
      (BMI = weight (kg)/height (m2)). The average BMI is higher in Finnish men (25.6)
      and women (24.6) than in their Swedish counterparts (24.6 and 23.2,
      respectively). In both countries, the average BMI is higher in men than in women
      below the age of about 55-64 years. In both countries and in both genders the
      average BMI is higher, the higher the age. The level of overweight as well as
      obesity is lower in Sweden than in Finland. Social class differences can be found
      in both countries. The odds ratio for overweight is higher in Finnish male and
      female farmers (OR = 1.57 and 1.94, respectively) as compared to upper white
      collars (OR = 1.0). In Sweden, high odds ratio for overweight can be found among
      male entrepreneurs (OR = 1.80) and female unskilled manuals (OR = 2.65). Obesity
      varies by social class in Swedish men and women as well as in Finnish women, but
      not in Finnish men. The results show that Finnish men and women are more often
      overweight and obese than their Swedish counterparts, but social class
      differences in overweight and obesity are larger in Sweden than in Finland.

PMID- 9581434
TI  - The F-Scan system with EDG module for gait analysis in the pediatric patient.
AB  - The Electrodynogram (EDG) system of foot-fall measurement has been in clinical
      use for more than 15 years. Recently the EDG was acquired by Tekscan, which
      manufactures the F-Scan system of foot-pressure analysis. The new F-Scan system
      with EDG module retains all of the benefits of the F-Scan system while
      incorporating the valuable temporal and pressure data comparisons offered by the
      EDG. This merging of technologies has resulted in a system that is more suitable
      for application in the pediatric patient than either system alone.

PMID- 9581433
TI  - Measurement of tibial torsion.
AB  - The anatomic accuracy of noninvasive in vivo measurement of tibial torsion was
      investigated through a comparison of goniometer measurements with those made on
      computed tomographic images. Seven normal subjects (2 women and 5 men; 14 legs)
      who ranged in age from 26 to 73 years were studied. The findings indicated that
      there was good agreement between measurements made by the two methods on the same
      limb. However, structural inconsistencies were found that cast doubt on the
      validity of certain anatomic reference points traditionally used in vivo studies
      of tibial torsion. In particular, use of the tibial tuberosity as a proximal
      reference may not give a true measurement of tibial or tibiofibular torsion.

PMID- 9581436
TI  - Pediatric peroneal spastic flatfoot in the absence of coalition. A suggested
      protocol.
AB  - While most pediatric patients with peroneal spastic flatfoot demonstrate tarsal
      coalitions, not all do. The absence of coalition may present a diagnostic
      challenge and make appropriate treatment difficult. Past and present etiologic
      theories, diagnostic modalities, and treatments are outlined in this article. The
      common peroneal nerve block is of great value in the diagnosis and treatment of
      peroneal spastic flatfoot with or without coalition. With adjunctive treatments,
      increased motion and decreased symptomatology are often obtained. A protocol,
      applied to five cases described herein, is suggested.

PMID- 9581435
TI  - Progressive subtalar joint dislocation and limb-length inequality. An unusual
      case.
AB  - Subtalar joint dislocation is a rare entity, accounting for only 1% of all
      traumatic dislocations. The authors report a case of an adolescent with gradual
      lateral subluxation of an anatomically abnormal subtalar joint with no history of
      trauma, an extremely rare presentation. The patient also had a congenitally short
      limb. The patient underwent llizarov leg lengthening along with multiple
      surgeries of the subtalar joint. The choice of the Ilizarov technique to lengthen
      the leg and realign the subtalar joint in this case is discussed.

PMID- 9581437
TI  - Wolf-Hirschhorn syndrome. Review of the literature and three case studies.
AB  - Wolf-Hirschhorn syndrome is a rare chromosomal abnormality caused by loss of
      material from the distal aspect of the short arm of chromosome 4. Characteristics
      include marked prenatal and postnatal growth retardation with psychomotor delay,
      profound mental deficiency, distinctive facies, and midline defects. Features
      that may affect the lower limb include lordosis, scoliosis, hypotonia, talipes
      equinovarus, and lesser-toe anomalies. This article reviews the literature on
      this rare syndrome and presents three case studies.

PMID- 9581438
TI  - Air quality and public health.

PMID- 9581439
TI  - Awareness of cancer-related programs and services among rural African Americans.
AB  - African Americans are at increased risk for cancer and represent an important
      target population for programs such as Healthy People 2000, the Cancer
      Information Service (CIS), and the 5 a Day for Better Health Initiative. Yet,
      awareness of such programs among rural blacks is unknown. This study assessed
      awareness of these programs and determined related knowledge and beliefs among
      rural African Americans. It was undertaken as part of the baseline survey for the
      Black Churches United for Better Health project, a National Cancer Institute
      funded initiative. A minority of respondents (n = 3737) demonstrated name
      recognition of Healthy People 2000 (23.4%), the CIS (42.4%), and the 5 a Day
      Program (40.7%). Far fewer (7.4%) were able to correctly identify the recommended
      daily number of servings of fruits and vegetables. Reported family history of
      cancer was associated with a greater tendency believe that eating more fruits and
      vegetables can prevent disease. These findings underscore the need for efforts to
      reach the rural black community with culturally sensitive and stage appropriate
      cancer prevention messages. Knowledge of family history of cancer may play an
      important role in targeting subgroups and delivering effective cancer prevention
      messages.

PMID- 9581440
TI  - Development of a multidisciplinary primary care program at the Drew University of
      Medicine and Science.
AB  - This article describes a required primary care curriculum for all third and
      fourth year medical students at the Drew/UCLA Medical Education Program. The
      curriculum is a supplement to the traditional medical school clinical
      requirements. Key features of the primary care core curriculum in the third year
      include a weekly half-day multidepartmental continuity clinic in a community
      health center serving underrepresented minority populations, a weekly didactic
      conference on primary care and society, a weekly clinical workshop on primary
      care skills, a weekly case review conference, and an orientation to primary care
      research methods. Fourth year medical students select a primary care
      subinternship that extends half days for 10 weeks in a community-based ambulatory
      care clinic. Fourth-year students also are required to select a mentor and
      conduct a research project on a primary care topic. Continuity of care records
      suggest that this program has been successful in allowing medical students to
      assume primary responsibility for a set of patients and to maintain significant
      levels of continuity of care over the course of the year. The evolution of the
      program, problems encountered, and anticipated changes in the curriculum are
      discussed.

PMID- 9581441
TI  - Race and the treatment of cytomegalovirus retinitis in a cohort of patients with
      acquired immunodeficiency syndrome.
AB  - This historical cohort study assessed the impact of race on critical factors in
      the diagnosis and drug treatment of cytomegalovirus (CMV) retinitis in acquired
      immunodeficiency syndrome (AIDS) patients over a 7-year period. The study
      subjects included 194 adult patients with a history of AIDS who were treated for
      CMV retinitis between September 1987 and September 1994. Abstracted inpatient
      hospital medical records and a statewide automated AIDS database were the primary
      sources of data. Patients were assessed for severity of CMV retinitis at
      diagnosis, time from initial CMV retinitis diagnosis to first treatment, survival
      from diagnosis of AIDS, and initiation of drug treatment for CMV retinitis.
      Results indicated a significant difference in the severity of CMV retinitis at
      diagnosis by race. Patients diagnosed with early disease were more likely to be
      white, whereas patients diagnosed with severe disease were more likely to be
      black. There was no difference in the type of CMV retinitis treatment or patient
      survival time after diagnosis, nor time to treatment once diagnosed by race.
      These results suggest that differences in survival may not be the result of
      discrimination against black patients and may be due more likely to practices
      associated with accessing medical treatment.

PMID- 9581442
TI  - Differential effect of ecologic risk factors on the low birthweight components of
      African-American, Mexican-American, and non-Latino white infants in Chicago.
AB  - This study explored the relationship between ecologic risk factors and infant
      birthweight. A stratified analysis was performed on all African-American, Mexican
      American, and white infants born in Chicago in 1990. One half of African-American
      mothers (n = 26,799) resided in communities with multiple ecologic risk factors,
      yet their very low birthweight rates were unaffected by the number of these
      factors. By contrast, only 5% of Mexican-American mothers (n = 9913) and 5% of
      white mothers (n = 13,596) lived in communities with multiple ecologic risk
      factors. Their very low birthweights were twice that of infants born to mothers
      who resided in communities with no ecologic risk factors. These results indicate
      that ecologic risk factors affect the very low birthweight rates of Mexican
      Americans and whites but not African Americans.

PMID- 9581443
TI  - Substance use disorders in an adolescent inpatient psychiatric population.
AB  - This study examined the comorbidity of substance use disorders and other
      psychiatric disorders in adolescent populations. The study population was
      comprised of 100 consecutive admissions, ages 13 to 17, to an acute care
      adolescent psychiatric inpatient unit for substance use disorders. Patients were
      assessed using the Personal Experience Screening Questionnaire (PESQ) and the
      substance-use disorder portion of the Structured Clinical Interview for DSM III-R
      (SCID-R). Thirty-three (33%) patients were identified as having a substance abuse
      or dependence diagnosis. There was no significant difference in the age between
      substance users and nonsubstance users. There were significantly more whites in
      the substance-using group. Sixty percent of all adolescents interviewed had
      histories of sexual or physical trauma, with trauma being significantly more
      common in the substance-using group. There were no significant differences in the
      number or type of other Axis I or Axis II diagnoses between the two groups. While
      substance users and nonsubstance users had no significant difference in the
      number of past psychiatric hospitalizations, nonsubstance users had significantly
      more past medical hospitalizations. These results indicate that high rates of
      comorbid substance abuse and psychiatric disorders exist in adolescents, and more
      in-depth study of comorbidity among adolescents is warranted.

PMID- 9581444
TI  - Predictive value of prior Rose angina for myocardial infarction confirmation
      after emergency admissions.
AB  - The Rose Questionnaire, developed to facilitate screening for the presence of
      coronary artery disease, has shown good utility for white men and more variable
      utility among Latino, African-American, and female subjects. This study
      investigated its utility for prediction of outcome in patients with suspected
      myocardial infarction. A total of 1428 white, Latino, and African-American
      subjects completed questionnaires after emergency admission, which were
      correlated with diagnoses at the time of discharge from a public hospital and
      private hospital. Results indicated that subjects with positive questionnaires
      were less likely to have infarction confirmed at discharge, except for those with
      a prior history of myocardial infarction, than those with a negative response.
      These data are important in evaluating the overall utility of the Rose
      Questionnaire and the significance of angina.

PMID- 9581445
TI  - Retrospective on community dentistry and public health at the University of
      Southern California (1966-1976), Part 1.

PMID- 9581446
TI  - Pennsylvania Medical Society Membership directory, 1997-98.

PMID- 9581447
TI  - Training issues.

PMID- 9581448
TI  - A fresh look at proportional mortality ratios.
AB  - This is a review of the use of proportional mortality ratios (PMRs). District
      health authorities rarely concern themselves with searching for unknown causes of
      disease but do need to monitor the health of a population. PMRs are a good way to
      do this. Textbooks of epidemiology tend to see PMRs as biased measures of risk
      and give them little attention. This review shows that the bias is small and of
      no practical importance. PMR studies can be seen as case-control studies and the
      major bias in these studies as analogous to Berkson's fallacy. We can then use
      the same techniques to reduce bias in PMR studies that are used in case-control
      studies. These are the use of several controls, the use of positive and negative
      controls, and the use of only one type of death in the denominator, rather than
      all causes of death. This article reviews these means of minimising bias using
      examples to show that careful selection of controls can overcome many of the
      supposed problems of PMR studies. It also shows how PMRs can control confounding
      in a way that SMRs cannot. PMR studies should be more widely used to monitor the
      health of the population.

PMID- 9581449
TI  - Colour blindness.
AB  - The physiology of colour vision is discussed; as is the way in which the human
      eye can detect various combinations of red, green and blue. Red-green colour
      blindness, with X-linked inheritance, is the most common, but other types are
      also considered. Methods of testing relating to the age of the child are
      reviewed. The use of colours in teaching is widespread, but there is controversy
      over the difficulties this may cause a colour blind child. A review of the
      literature does not reveal much information on this, and any problems that do
      arise are likely to be individual to the child, and to depend on such factors as
      overall intelligence, the attitude of the teacher, and the personality of the
      child. There is not doubt that it is essential to recognise colour vision defects
      when it comes to choosing a career, and that tests must be done during secondary
      schooling, but in order to avoid some affected children being disadvantaged there
      is enough evidence to support testing at school entry.

PMID- 9581450
TI  - Early life and later determinants of adult disease: a 50 year follow-up study of
      the Newcastle Thousand Families cohort.
AB  - The relative contribution of socioeconomic, behavioural and biological factors
      operating in fetal and infant life, childhood and adulthood to risk for
      cardiovascular disease, respiratory diseases and non-insulin-dependent diabetes
      in middle age has become an important research issue. All 1142 babies born in
      Newcastle upon Tyne in May and June 1947 were recruited into a prospective cohort
      study of child health (the 'Thousand Families' study) and followed in great
      detail to the age of 15 y, with a brief further follow up at age 22 y. Children
      from poorer families were at greatest risk of severe respiratory tract infection
      in infancy. Children from professional and managerial families were on average
      taller and heavier throughout childhood than those from semi- and unskilled
      manual social classes. Repeated infections in early childhood greatly increased
      the risk of developing chronic respiratory disease by age 15 y. This paper
      outlines a new investigation designed to trace surviving members of this cohort
      and to chart the relationships between their socioeconomic circumstances,
      lifestyles, experiences and health from birth through to the present day.
      Existing data on socioeconomic circumstances and infections in infancy and
      childhood, infant nutrition, birthweight and physical development to age 22 y
      will be linked to information gained from a new study. This comprises a postal
      questionnaire survey of study members' adult health, socioeconomic circumstances
      and lifestyle, and a hospital based clinical examination including heart and lung
      function, glucose tolerance, blood lipids and anthropometric measurements at age
      49-51 y. Out of a target sample of 979 people for whom sufficient data are
      available on the first year of life, 866 (88%) have been traced and 649 are still
      resident in the North of England. Those study members who have been traced are
      highly representative of the original cohort. The Thousand Families cohort
      provides a unique opportunity for detailed epidemiological study because of the
      wealth of data available on infant and childhood socioeconomic and family
      circumstances, all of which was collected prospectively. In addition, there has
      been comparatively little loss to follow-up since 1948.

PMID- 9581451
TI  - Definition of healthy eating in the Spanish adult population: a national sample
      in a pan-European survey.
AB  - A national survey was carried out to find out how the Spanish adult population
      defined 'healthy eating'. Consumers were asked to describe in their own words
      what 'healthy eating' means to them. The sample included 1009 Spanish subjects
      over 15 y of age selected by a multietapic procedure. This study belongs to the
      Spanish partnership in a pan-European survey about attitudes to food, nutrition
      and health coordinated by the Institute of European Food Studies of Dublin. The
      results were shown as the percentages of the sample who gave one of the five most
      frequently mentioned descriptions ('more vegetables', 'balanced diet', 'more
      fruit', 'less fat' and 'more fish') and the distribution of responses by age,
      sex, region, socio-economic level and education level. A multivariable logistic
      regression model was fitted to assess the characteristics independently related
      to the use of the definition 'balance and variety' for healthy eating. The
      majority of the Spanish people defined 'healthy eating' as a diet with 'more
      vegetables' as the main description. Other descriptions commonly mentioned were
      'less fat', 'more fruit', 'more fish', and 'more lean meat'. A higher age was
      associated with a lower likelihood of mentioning the concept of balanced diet. A
      higher educational level was also independently and strongly related to a higher
      prevalence of this definition. Differences between men and women showed only
      borderline significance. Our results suggest the need to improve nutritional
      education about fiber, low fat and cholesterol. It would be interesting to
      develop strategies in Spain to educate people on a definition of 'healthy eating'
      based upon 'balance and variety'.

PMID- 9581452
TI  - Economic burden of stroke and the evaluation of new therapies.
AB  - Stroke is a major health problem in all industrialised countries and evidence is
      mounting that this problem also affects the developing countries. In the
      industrialised countries, it is the third largest killer and, of the survivors,
      about one-half are left with a permanent handicap. Despite the huge burden of
      stroke on healthcare and social services (several USA studies estimate the annual
      cost of stroke to be between US $6.5 and 11.2 billion) the cost of strokes has
      aroused little attention. An absence of effective therapies may be one of the
      reasons for this lack of interest; the costs have been taken as inevitable. With
      the advent of new therapies for acute ischaemic stroke (thrombolytics and
      neuroprotectants) there is renewed interest in improving both the management and
      outcome for patients. Key to the evaluation (both clinical and economic) of new
      stroke therapies is the choice of evaluation scales/instruments. Increasingly,
      stroke investigators are using measures of functional outcome (for example the
      Barthel index) as a primary endpoint in stroke trials. This is pertinent, as
      functional outcome has been found to reflect reasonably well the degree to which
      a patient needs support after stroke, irrespective of whether this is provided by
      the family or society.

PMID- 9581453
TI  - Can marital selection explain the differences in health between married and
      divorced people? From a longitudinal study of a British birth cohort.
AB  - In view of the rising divorce rates, the impact of divorce on health has an
      increasing importance in public health. The differentials in health between the
      married and the divorced may be explained by 'marital selection' and 'marital
      protection'. Using longitudinal data from a study of the 1958 British birth
      cohort, factors that select people into divorce were identified from the areas of
      socio-economic status, health, and attractiveness, which included physical
      attractiveness, health-related behaviour and temperament. Evidence for both
      positive and adverse selection is found. The different sets of selection factors
      for females and males appear to be in line with gender role expectations. The
      health differentials between married and divorced men were weak and can be
      explained away by the selection factors. Having controlled for the selection
      effects, there were still significant associations between divorce and physical
      and psychological health in women. Though these unexplained differentials cannot
      be definitely interpreted as the consequences of marital dissolution, this
      interpretation remains plausible.

PMID- 9581454
TI  - Epidemiology of paragonimiasis in Cross River basin, Nigeria: prevalence and
      intensity of infection due to Paragonimus uterobilateralis in Yakurr local
      government area.
AB  - Prevalence and intensity of paragonimiasis among inhabitants of the Yakurr Local
      Government Area in the Cross River basin of Nigeria is reported. Diagnosis was
      based on a single sample detection of eggs of Paragonimus in 5 ml of sputum.
      12.27% out of 880 subjects were infected. The infections were due to Paragonimus
      uterobilateralis. Prevalence of the infection increased with age, up to a peak
      prevalence of 23.75% (19 out of 108) among subjects between the ages of 17-22 y
      old. Thereafter, it declined progressively with increase in age to much lower
      values such that by the age of 53-58 y old, infection had fallen by more than
      75%. Prevalence of the infection was significantly higher among females, 13.80%
      (58 out of 108), than males 11.36% (50 out of 108) (P < 0.009). Intensity of
      infection (eggs/5 ml sputum) ranged from 12-123 eggs/5 ml.sputum, with subjects
      between the ages of 17-22 y old being the most heavily infected group. Prevalence
      and intensity of the infection were positively correlated (P < 0.497). The need
      for control measures to reduce human suffering due to infections in the area,
      particularly among women and children is emphasized.

PMID- 9581455
TI  - Observations of sexually transmitted disease consultations in India.
AB  - OBJECTIVES: To assess the quality of sexually transmitted disease (STD) case
      management provided in public and private health facilities in selected areas of
      Madras, Tamil Nadu, India, in order to make recommendations for improving the
      quality of care and promote the syndromic approach to STD treatment. METHODS:
      Structured observations of consultations for STDs in health care facilities.
      Scoring of the observations according to standards for history taking,
      examination, treatment and provision of basic health promotion advice allows
      evaluation of STD case management. RESULTS: With STD treatment adequacy scored
      against Indian national guidelines (which recommend aetiologic treatment),
      history taking, examination and treatment were satisfactory in 76 out of 108
      (70%) of observed consultations. However, if STD treatment adequacy is scored
      with respect to the syndrome approach towards selected STD (male urethritis and
      non herpetic genital ulcer for both sexes), only 8 out of 81 (10%) of the
      patients were satisfactory managed. During 32 out of 108 (30%) of the
      consultations, advice on the use of condoms in order to prevent STD or HIV/AIDS
      was given. Instructions regarding how to use condoms were offered to seven (6%)
      patients and condoms were only provided to one patient (1%). Patients were urged
      to refer their partner(s) for treatment during 29 (27%) of consultations. A
      criterion of adequate use of the STD consultation for health promotion, requiring
      both promotion of condoms and encouragement to refer partner(s) for treatment,
      was met during 13 (12%) of consultations. CONCLUSIONS: Monitoring and improving
      the standards of care at facilities at which STDs are treated have become key
      roles of STD/HIV/AIDS programmes. The present report suggests that in Madras the
      activities of medical practitioners who treat STD patients are far from ideal at
      present. Improvements would involve simplifying existing treatment guidelines by
      promoting the syndromic approach to STD management, continuing education
      programmes for health care providers in the public and private sectors and repeat
      assessments and feedback of the quality of STD care.

PMID- 9581456
TI  - A SAS macro for a simulation study of imputation methods for missing values--an
      application of Bebbington's algorithm.
AB  - This paper presents a SAS macro for a simulation study of comparing a new variant
      of hot-deck imputation with mean imputation for missing values, in which a simple
      algorithm proposed by Bebbington (Applied Statistics, 1975) for carrying out
      simple random sampling without replacement was employed to draw repeated random
      samples efficiently. A simulated example of drawing repeated random samples from
      a regional survey of obesity in school children was used to demonstrate the SAS
      macro.

PMID- 9581457
TI  - Continuity of public health leadership and population health outcome.

PMID- 9581458
TI  - Lithogenecity of bile in the pathogenesis of cholelithiasis.
AB  - The authors have made a review of the present literature relating to lithogenic
      bile as the main pathogenic factor in the creation of cholelithiasis. Lithogenic
      bile is formed in result of complex biochemical reactions taking place in bile
      under physiological conditions, as well as in pathology of the liver and the
      biliary tract. Significant clinical implications result from the analysis.

PMID- 9581459
TI  - Cord blood IgE levels as a predictive value of the atopic disease in early
      infancy a review article.
AB  - The article reviews the recent opinions concerning the predictive value of high
      cord blood IgE (cIgE) concentrations in the development of atopic disease in
      infancy and childhood. The results of data from different scientific centers
      remain still controversial. There is a general agreement that a high neonatal IgE
      concentration is connected with later allergic disease but low positive
      predictive value (PPV) of elevated cIgE makes cIgE determinations unuseful for
      general screening test.

PMID- 9581460
TI  - An improved method for chemical deglycosylation of gastric mucus glycoprotein.
AB  - We describe an improved method for chemical deglycosylation of gastric mucin
      which involves: reduction, alkylation, desialylation, periodate oxidation with
      beta-elimination and two-steps of TFMSA/anisole treatment. The product was 96%
      deglycosylated protein with amino acid composition similar to purified mucin with
      apparent molecular weight of 90 kDa.

PMID- 9581461
TI  - The effects of reductive dissociation of gastric mucin isolated in the presence
      of proteinase inhibitors.
AB  - Mucin was purified by the gel filtration method on columns with high porous
      molecular sives in buffers with SDS and proteinase inhibitors. The addition of
      proteinase inhibitors distinctly inhibited proteolytic activity. It was found
      that the obtained mucin, after disulphide-bound reduction, is dissociated to
      mucin subunits and N-glycosylated glycoprotein of molecular weight about 75 kDa.
      This protein has carbohydrate and amino acid composition different from high
      molecular fraction. The 75 kDa protein is strongly associated with high molecular
      mass mucin subunits and can be separated either during electrophoresis or
      fractionation in buffers with 2-mercaptoethanol.

PMID- 9581462
TI  - C-reactive protein concentration in the sera of pregnant women with imminent
      premature parturition and preterm amniorrhea.
AB  - C-reactive protein (CRP) levels were evaluated during spontaneous labour, in
      imminent premature parturition (IPP) and after preterm rupture of oocyst
      membranes (PROM). Increasing CRP level during spontaneous labour was found in
      16.6% parturients. Elevated CRP level in patients with IPP makes it impossible to
      predict premature labour. In parturients with PROM, increase in CRP level makes
      further infection predictable only in a few cases.

PMID- 9581463
TI  - Fungi in water reservoirs of the Western Suwalki Lake District and in some
      adjacent water basins.
AB  - In the years 1991-1995 the authors investigated the mycoflora and the effect of
      environmental factors of 36 lakes and 4 rivers in the Western Suwalki Lake
      District. In addition the effect of environment factors on the occurrence of
      various aquatic fungi was analysed. Altogether of 109 fungi species were
      recorded. Twenty two species new the mycoflora of Poland were noted. The presence
      of Tripospermum myrti in Lake Oleckie Wielkie is noteworthy.

PMID- 9581464
TI  - Lysozyme in ulcerative colitis.
AB  - Studies were carried out on the neutrophil activity in a course of ulcerative
      colitis. Activity of lysozyme in blood serum as a granulocyte-derived enzyme was
      assessed. The studies included 60 patients who had 82 relapses and 11 patients
      with remissions. They were classified into mild, moderate and severe relapse
      according to severity of disease. Increased activity of lysozyme in blood serum
      was shown. That may indirectly prove the role of functional state of neutrophils
      in the disease.

PMID- 9581465
TI  - Nitroblue tetrazolium test in course of ulcerative colitis.
AB  - Studies were carried out on the neutrophil activity in a course of a ulcerative
      colitis (UC). Phagocytic ability of granulocytes was assessed in spontaneous and
      stimulated nitroblue tetrazolium (NBT) reduction test. The studies included 60
      patients who had 82 relapses and 11 patients with remission. They were classified
      into mild, moderate and severe relapse according to severity of disease.
      Increased phagocytic ability of neutrophils in spontaneous and stimulated NBT
      reduction test was shown.

PMID- 9581466
TI  - Alpha-fetoprotein serum concentration in different stages of liver cirrhosis.
AB  - Serum alpha-fetoprotein (AFP) concentration was measured in 41 patients with
      different stages of liver cirrhosis demonstrated through scored Child-Pugh
      classification. Mean value was elevated up to 65.9 21.9 U/l, butstatistically
      significant difference in comparison with control group was observed only in
      patients classified as Child-Pugh C. AFP concentration revealed significant
      positive correlation with score values. Dynamics of AFP during one-year follow up
      demonstrated three-fold and statistically significant increase of its
      concentration, that was accompanied by elevation of mean score values.

PMID- 9581467
TI  - Hyperthyroid goitre treated surgically.
AB  - The aim of the study was the comparative analysis of the degree of intensity of
      male and female hyperthyroidism treated surgically in the years 1990 to 1996. In
      this period 295 females and 42 males underwent operation for hyperthyroid goitre.
      Female predominance was noted in hyperthyroidism (ratio 7:1), in Graves' disease
      (7.4:1) and in toxic nodular goitre (6.3:1). The clinical findings in pre- and
      postoperative patients, including laboratory, visual diagnosis, and intra- and
      postoperative complications were evaluated. In the preoperative period, the
      incidence of the thyreocardiac syndrome was greater in the male. Male
      hyperthyroidic goitres were more frequently located retrosternally and caused
      trachea compression. No significant sexual differences were found in routine
      laboratory tests. Operations for hyperthyroidic male goitres usually caused more
      intraoperative problems and were connected with greater blood loss. Estimation of
      cardio-vascular parameters in the early postoperative period showed higher
      intensification of hyperkinetic circulation and higher mean body temperature in
      men. Signs of psychosis developed postoperatively in two men. The analysis of
      patients with hyperthyroidic goitre treated surgically revealed more severe
      course of male thyreotoxicosis in the perioperative period.

PMID- 9581468
TI  - The ability of human polymorphonuclear cells (PMNS) to release of soluble IL-6
      receptor (IL-6sR) in response to different stimuli in vitro.
AB  - In the present work we have examined the release of soluble IL-6 receptor (IL
      6sR) by polymorphonuclear cells (PMNs) in response to different stimuli: zymosan,
      ConA, PHA and LPS. We have also investigated the generation of IL-6sR by whole
      blood cells (WBC) under the same condition of the culture. IL-6sR secreted by
      PMNs and WBC were detected in cell-free supernatants by ELISA. Results of our
      investigation revealed that freshly isolated PMNs from healthy subjects exhibit a
      different ability to the secretion of IL-6sR in response to used stimuli. LPS
      showed the most significant effect on the IL-6sR secretion by PMNs and WBC as
      compared to the other inducers. The mean concentrations of IL-6sR released by
      PMNs were lower than concentrations of IL-6sR released by WBC. Measurements of
      the IL-6sR secretion by immunocompetent cells appear to be useful in the
      estimation of the cellular activity mediated by IL-6.

PMID- 9581469
TI  - Soluble IL-6 receptor release by PMNs and PBMC in patients with oral cavity
      cancer.
AB  - It is known that the main source of cytokine and soluble cytokine receptors are
      mononuclear cells in the peripheral blood. Data including the release of soluble
      mediators by polymorphonuclear cells (PMNs) are controversial. In these
      examinations using an in vitro model, we studied the ability of spontaneous and
      LPS-stimulated PMNs to the release of soluble IL-6 receptor (IL-6sR) in oral
      cavity cancer patients. Obtained results were compared to the release of IL-6sR
      by a peripheral blood mononuclear cells (PBMC) and the serum levels. The
      concentrations of IL-6sR in the culture supernatants of cells and in the serum
      were tested by ELISA. The culture supernatants of spontaneous and LPS-stimulated
      PMNs derived from oral cavity cancer patients contained an insignificant lower
      concentrations of IL-6sR than those from healthy subjects. The concentrations of
      IL-6sR released by PBMC were higher than those released by PMNs in both control
      and patient groups. There was correlation between the amounts of IL-6sR in the
      culture supernatants of spontaneous PMNs and PBMC. The altered ability of PMNs
      and PBMC to the release of IL-6sR may influence the immune response of host to
      tumor mediated by IL-6.

PMID- 9581471
TI  - Preparation of benzyl 2-benzyloxycarbonylamino-4-dichloroacetamido-2,4-dideoxy
      alpha- D-xylopyranoside, substrate for the synthesis of the heterocyclic analogue
      of chloromycetin.
AB  - The paper describes the eleven stage synthesis of the derivative (XI) of 2,4
      diamino-2,4-dideoxy-D-xylose, containing amino groups selectively substituted by
      two different acyls. The initial substrate was L-arabinose. The compound
      obtained, after removing the blocking groups, constitutes a semiproduct for the
      synthesis of the pyrrole analogue of chloromycetin by the Knorr method.

PMID- 9581470
TI  - Alcohol dehydrogenase (ADH) activity in the sera of patients during the course of
      viral hepatitis.
AB  - Total alcohol dehydrogenase activity in the sera of 77 patients in the course of
      viral hepatitis was determined by means of photometric method based on p
      nitrosodimethylaniline reduction. Blood samples were taken 5 times at intervals
      of 7 to 9 day. We found that serum total ADH activity was higher at the onset of
      disease than that of the control group. The highest increase of activity was
      observed in the first week of hospitalisation, and exceeded the mean control
      value about 7 times. After that, the activity of ADH gradually decreased, and
      reached the value of the control group in the last period of the study. During
      five weeks of the study the total activity of ADH showed a good linear
      correlation with alanine and aspartate aminotransferases. We concluded that total
      alcohol dehydrogenase activity measured by photometric method increase in the
      course of viral hepatitis and correlate with the progress and treatment of
      disease measured by commonly accepted enzymatic markers of liver cell damage.

PMID- 9581472
TI  - Synthetic analogues of netropsin and distamycin. IV. Synthesis of a new
      carbocyclic analogue of distamycin with alkylating side groups.
AB  - A carbocyclic analogue of distamycin was obtained, in which the N-methylpyrrole
      rings were substituted by disubstituted benzene rings. Additionally, N-chloro- or
      N-bromoacetyl groups, displaying alkylating properties, were introduced. The
      synthesis, starting from 3,5-dinitrobenzoyl chloride, consisted of five stages.

PMID- 9581473
TI  - The bactericidal activity of blood platelets in patients infested with Entamoeba
      histolytica/Entamoeba dispar.
AB  - Blood platelets participate actively in organism defensive reactions and
      particularity in antiparasitic immunity. Platelets stimulation can be the result
      of contact with a parasite, the presence of immunoglobulins, complement and
      lymphokines. The aim of the study was to evaluate the blood platelets
      bactericidal activity in the course of amoebiasis. The examination was carried
      out in the group of 22 patients with E. histolytica/E. dispar, diagnosed on the
      basis of cyst forms presence in faeces. The results show that blood platelets
      bactericidal activity is significantly impaired in the course of amoebiasis.

PMID- 9581474
TI  - Prolidase as a prodrug converting enzyme I. Synthesis of proline analogue of
      chlorambucil and its susceptibility to the action of prolidase.
AB  - The feasibility to targeting prolidase as an antineoplastic prodrug-converting
      enzyme has been examined. The synthesis of proline analogue of chlorambucil (well
      known antineoplastic agent) conjugated through imido-bond (potential target for
      prolidase action) has been performed. It was found that the product of synthesis,
      N-[4-[4-(N,N-bis(2-chloroethyl)amino) phenyl]butyryl]-L-proline is insoluble in
      aqueous solutions but it may be solubilized in methanol. The methanol in 30%
      concentration reduces catalytic activity of prolidase to 40% of values found in
      aqueous solution, although it allows in such conditions the measurement of
      substrate susceptibility to the action of this enzyme. It has been presented that
      product of synthesis is weakly susceptible to the action of purified prolidase,
      comparable to the susceptibility of glycyl-L-hydroxyproline. Although
      insolubility of the proline analogue of chlorambucil in aqueous solutions limit
      its potential therapeutic value, the presented data suggest that prolidase may
      have a broader substrate specificity. It suggests that targeting of prolidase as
      a prodrug-converting enzyme may serve as a novel strategy in therapy of various
      diseases.

PMID- 9581475
TI  - Pathological changes in rats hepatocytes on acute lindane poisoning.
AB  - Histological, histochemical and ultrastructural examinations of the liver were
      carried out on rats. The animals were given crystalline lindane intragastrically,
      in a dose evoking acute intoxication, (1/3 LD50). Then the rats were decapited
      after 1, 3, 10, 20 and 36 days following pesticide administration. The obtained
      results indicate, that acute lindane intoxication produces morphological changes
      in the rat liver, which evidence a disturbance inenergetic processes of
      hepatocytes and they are reversible and adaptative.

PMID- 9581476
TI  - Intravital treatment of the pulp with simultaneous laser biostimulation.
AB  - The aim of the study was clinical and radiological evaluation of the pulp
      treatment using direct capping and amputation under anaesthesia with simultaneous
      laser biostimulation. Thirty procedures were performed using laser and thirty-six
      without it. In all cases non-setting Ca(OH)2 was applied as a biological
      dressing. The results obtained provide justification for the application of laser
      biostimulation to biological treatment of the pulp.

PMID- 9581477
TI  - Hyphomycetes in morning dew of meadows.
AB  - Hyphomycetes in morning dew of meadows in northeastern Poland. The authors
      investigated of the Hyphomycetes in morning dew of meadows grass in the morning
      hours of sunny days in May and September 1994. The presence 23 Hyphomycetes
      species was noted. The following fungi were recorded for the first time from
      Poland: Blodgettia borneti, Canalisporium elegans, C. pulchrum, Paraepicoccum
      amazonense and Sporidesmium basiacutum.

PMID- 9581478
TI  - Hyphomycetes in the water of peatmoss (Sphagnum).
AB  - The authors investigated hyphomycetes in the water of peatmoss (Sphagnum)
      collected from forest peatbogs in the Augustowska and Knyszynska Forests in
      northeastern Poland. The presence of 28 hyphomycete species was noted. Cordana
      musae, Helicoon macrosporum, Sporidesmiella aspera, Stemphyliomma tambopataense
      and Tripospermum pes-gallinae were recorded for the first time from Poland.

PMID- 9581479
TI  - The influence of tobacco parental smoking on serum IgE level of their offspring.
AB  - This study was designed to evaluate the influence of passive smoking on serum IgE
      level and on incidence of atopic diseases in infants. Eighty two infants and
      their families were studied. The cigarette smoking was recorded in 28% of mothers
      and in 62% of fathers. Both parents were smokers in 20 families (24%). An
      elevated total serum IgE level was demonstrated significantly more frequent in
      the children of smoking mothers (p < 0.05). Paternal smoking did not influence
      neither serum IgE level nor incidence of atopic diseases.

PMID- 9581480
TI  - The incidence and clinical manifestation of food allergy in unselected Polish
      infants: follow-up from birth to one year of age.
AB  - This study was intended to evaluate the incidence of atopic diseases and spectrum
      of clinical allergic manifestation in Polish infants from North-East region of
      Poland in relation to genetic hereditance. The infants included in the study were
      unselected, born consecutively during the first three months of 1993. It was
      demonstrated that 39% of infants developed an atopic disease during first year of
      life, 70% in high-risk of allergy group and 18% in low-risk of allergy group. The
      difference was statistically significant (p < 0.0005). The common atopic
      manifestation in children was atopic dermatitis. It was recorded in 70% of babies
      with and in 12% of babies without a family history of atopy.

PMID- 9581481
TI  - Effect of endotoxin on the concentration of triacylglycerols in the liver of the
      rat.
AB  - The aim of the present study was to examine an effect of endotoxin E.coli O127:B8
      on the concentrations of triacylglycerol (TG) in the rat's liver. The rats were
      divided into the following groups: control, treated with one dose of endotoxin,
      treated with three doses of endotoxin. The rats had free access to food (pallet
      diet for rodents) and water. Endotoxin E.coli O127:B8 was injected
      interperitoneally in dose of 3 mg/kg b.w.--once or three times at intervals of 72
      hrs. One dose of endotoxin decreased blood serum TG concentration, although the
      concentration of liver TG was increased after 24 hrs. Triple doses of endotoxin
      given at 72 hrs intervals increased the blood serum TG concentration after 24
      hrs, but had no effect on the liver concentration.

PMID- 9581482
TI  - Activity of lysosomal and nonlysosomal proteases of fibrosarcoma induced by
      methylcholanthrene.
AB  - Activity of lysosomal (cathepsins A,B,C,D and E) and nonlysosomal proteases
      (cathepsin G, elastase, collagenase, prolidase, prolinase) was evaluated in
      fibrosarcoma induced in rats by methylcholanthrene. No differences were found in
      the activity of the examined proteases in tumours of different size in the
      external, intermediate and central spheres of these tumours. Activity of
      cathepsins A,B,C,D,E and G, prolidase and prolinase was higher in the
      fibrosarcoma and activity of collagenase and elastase was lower than in the rat
      skin.

PMID- 9581484
TI  - Serum cholinesterase activity in children with gastroduodenitis or peptic ulcer
      disease.
AB  - Serum cholinesterase /ChE/ investigation in children with gastroduodenitis or
      peptic ulcer disease indicate its low activity, specially in children with peptic
      ulcer disease. These investigation can be index of parasympathetic tonus in
      digestive tract disease.

PMID- 9581485
TI  - The alterations in the activity of amylase and its salivary isoenzyme in the
      serum of patients with ovarian carcinoma, submitted to radiotherapy.
AB  - Total activity of alpha-amylase and its salivary isoenzyme in the serum of
      patients with ovarian carcinoma of various types were evaluated before
      radiotherapy, in the middle of radiotherapy period, in the last day and 2 months
      after radiotherapy. Before radiotherapy the activity of these enzymes were
      significantly higher in patients with ovarian serous cystadenocarcinoma. It was
      found that irradiation resulted in a decrease of both total amylase activity and
      its salivary isoenzyme in the serum. The proportional participation of salivary
      isoenzymes in total amylase activity was normalized. It is suggested that the
      assay of salivary alpha-amylase activity may be useful in the evaluation of
      radiotherapy effectiveness.

PMID- 9581483
TI  - Activity of lysosomal and nonlysosomal proteases and contents of protein and its
      degradation products in the blood serum of rats with fibrosarcoma induced by
      methylcholanthrene.
AB  - Activity of lysosomal and nonlysosomal proteases and contents of protein and its
      degradation products in the blood serum of rats with methylcholantrene
      fibrosarcoma were evaluated. Activity of lysosomal proteases and prolidase and
      prolinase as well in the blood serum of rats with methylcholanthrene tumour did
      not differ from the activity of these enzymes in the blood serum of control rats.
      Only the activity of elastase and collagenase in the blood serum of rats with
      methylcholanthrene tumour especially with tumour of intermediate and big mass was
      increased. Content of total protein was decreased in the blood serum of rats with
      tumour of intermediate and big mass and contents of glycoproteins and alfa-amin
      nitrogen were increased in comparison to the blood serum of control rats.

PMID- 9581486
TI  - Effect of topical miconazole in plaque psoriasis.
AB  - The aim of this study was the assessment of efficacy and tolerance of topical
      miconazole in plaque psoriasis. 9 patients aged 23-63 years with diagnosis of
      plaque psoriasis were enrolled. 2% miconazole cream was applied twice daily from
      7 to 12 weeks (under occlusive dressing to obtain optimal penetration of the
      drug) in the plaque with a minimum diameter of 5 cm. In most patients clinical
      improvement of the topical miconazole treatment was observed.

PMID- 9581487
TI  - Colour doppler sonography guided percutaneous fine-needle biopsy of the liver.
AB  - Between 1992 and 1997, every year, approximately 30,000 examinations of the liver
      and bile ducts were done. Addition of colour Doppler imaging improves safety of
      procedures and allowed to perform ultrasound guided biopsy in 73 patients. On the
      basis of our experience we state that colour Doppler sonography guided
      percutaneous fine needle biopsy of the liver is useful, sufficient and safety
      diagnostic method of abscesses, cysts and malignant tumours of the liver.

PMID- 9581488
TI  - Assessment of bone density in children with Scheuermann's disease.
AB  - Twenty four children with Scheuermann's disease (11 girls and 13 boys) aged 9-18
      years measured for bone mineral density. The total skeleton (TB BMD) and lumbar
      spine (L2-L4 BMD) mineral density were investigated by dual energy X-ray
      absorptiometry (DEXA). In nine patients with Scheuermann's disease and backache
      we found lower levels of TB BMD and L2-L4 BMD in comparison with reference
      population of Lunar database. Osteopenia in these children may be caused by
      decreased physical activity due to vertebral pain.

PMID- 9581489
TI  - Serum beta 2-microglobulin in patients with trichinosis.
AB  - beta 2-microglobulin (beta 2-m) has been identified as the light chain of the
      class I major histocompatibility complex proteins, which plays an important role
      in immune response, especially in T-lymphocytes activation. The aim of the study
      was to evaluate serum beta 2-m concentration in patients with trichinosis in
      different phases of this illness. beta 2-m was determined with ELISA in 7
      patients twice: in the first week of the hospitalization during acute phase of
      trichinosis and 21-25 days later, after abatement of clinical signs. It was found
      that beta 2-m was significantly elevated at the beginning of the illness and
      decreased, but in the fourth week of the hospitalization it was still high. There
      was a positive correlation between beta 2-m and absolute count of eosinophils in
      blood in the first (r = 0.77, p < 0.05) and in the fourth week of hospitalization
      (r = 0.65, p < 0.05). It is concluded that beta 2-m may have certain importance
      in the activation of eosinophils and may serve as a marker of immune activation
      in the course of trichinosis.

PMID- 9581490
TI  - Effects of ranitidine or nocloprost on the selected gastric juice components in
      the patients with the gastric ulcer.
AB  - The 24 patients with gastric ulcer were treated ranitidine (2 x 150 mg daily) or
      nocloprost (2 x 200 micrograms daily). The effects of these drugs on the gastric
      juice components were measured. We evaluated hydrochloric acid, total protein,
      pepsin and some carbohydrates components secretion. We showed, that ranitidine
      decreased significantly total protein, fucose, N-acetylneuraminic acid and
      hexoses contents in the gastric juice in the basal secretion; the same tendency
      was observed in the pentagastrin-stimulated secretion. The similar direction of
      the changes, but weakly expressed was confirmed in the patients treated with
      nocloprost. It has been shown, that ranitidine modified the gastric mucin
      components content, what can suggest diminished degradation of mucus directly
      adhering to the gastric mucosa.

PMID- 9581491
TI  - Influence of endotoxin on the level of tumor necrosis factor alfa and blood
      morphology in rats.
AB  - The influence of endotoxin E.coli O127 B:8 given intravenously or
      intraperitoneally on the level of Tumor Necrosis Factor alfa (TNF-alpha), blood
      cells count and bone marrow morphology in rats was studied. The presented results
      show that endotoxin (3 mg/kg) given intravenously or intraperitoneally (1 or 3
      times) provoked an appearance of TNF-alpha in the systemic circulation 24 hours
      after its injection. Endotoxin given intravenously evoked greater changes in
      blood morphology and bone marrow than that applicated intraperitoneally.

PMID- 9581492
TI  - [Therapy or euthanasia? How far may (and should) the veterinarian go in the
      treatment of an animal?].
AB  - Veterinarians are often faced with the question of whether they should treat or-
      in accordance with the animal owner--to end the life of a pet animal. This
      situation can be described as a moral dilemma. Can this moral dilemma be solved?
      The author argues that we have special moral obligations to care for pet animals.
      The special, quasi-personal relationships between pet animal and animal owners
      provide veterinarians in most cases with moral reasons to carry out the
      treatment.

PMID- 9581493
TI  - [Cancer eye in cattle: 21 cases (1990-1996)].
AB  - Between 1990 and 1996, 21 cows suffering from cancer eye had been admitted to the
      Clinic for Food Animals and Horses, University of Bern. Case history and
      localization and dimension of the tumor at admission were evaluated. Treatment
      consisted of bulbus extirpation in 17 of 21 cows. In two cows, cryosurgery was
      performed, while two cows were slaughtered for economic reasons. Telephone follow
      up inquiries were performed between 10 and 84 months after surgery. Mean survival
      time after surgery was 15 months. Recurrence of the tumor was evident in six
      cases within 2 to 14 months after surgery. We recommend bulbus extirpation in
      cows with cancer eye to extend productive life.

PMID- 9581494
TI  - [Two cases of renal amyloidosis in the shar pei].
AB  - The variability of the symptomatology and of the lesions of renal amyloidosis of
      the shar pei is described together with difficulty of making the diagnosis.

PMID- 9581495
TI  - [What is your diagnosis? Foreign body in the stomach of a dog].

PMID- 9581496
TI  - [Case report: Eisenmenger syndrome in a 9-month-old border collie puppy].

PMID- 9581497
TI  - Protein methylation: a signal event in post-translational modification.

PMID- 9581498
TI  - Mechanism of autoproteolysis at the NS2-NS3 junction of the hepatitis C virus
      polyprotein.

PMID- 9581500
TI  - PIP2: activator ... or terminator of small G proteins?

PMID- 9581499
TI  - The origin and evolution of oxygenic photosynthesis.
AB  - The evolutionary developments that led to the ability of photosynthetic organisms
      to oxidize water to molecular oxygen are discussed. Two major changes from a more
      primitive non-oxygen-evolving reaction center are required: a charge-accumulating
      system and a reaction center pigment with a greater oxidizing potential.
      Intermediate stages are proposed in which hydrogen peroxide was oxidized by the
      reaction center, and an intermediate pigment, similar to chlorophyll d, was
      present.

PMID- 9581501
TI  - Two forms of type IV zinc-finger motif and their kingdom-specific distribution
      between the flora, fauna and fungi.

PMID- 9581502
TI  - Contrasting routes of c-type cytochrome assembly in mitochondria, chloroplasts
      and bacteria.
AB  - The biogenesis of bacterial c-type cytochromes generally involves many gene
      products--some of which may also have roles in other processes--and their
      interaction with the disulphide-bond-forming system of the bacterial periplasm.
      However, in some bacteria a simpler process appears to operate that might be
      related to the formation of c-type cytochromes in thylakoids of photosynthetic
      cells. The corresponding process in fungal mitochondria is distinct.

PMID- 9581504
TI  - Metabolic databases.

PMID- 9581503
TI  - Specificity, free energy and information content in protein-DNA interactions.
AB  - Site-specific DNA-protein interactions can be studied using experimental and
      computational methods. Experimental approaches typically analyze a protein-DNA
      interaction by measuring the free energy of binding under a variety of
      conditions. Computational methods focus on alignments of known binding sites for
      a protein, and, from these alignments, make estimates of the binding energy.
      Understanding the relationship between these two perspectives, and finding ways
      to improve both, is a major challenge of modern molecular biology.

PMID- 9581505
TI  - The DNA replication problem, 1953-1958.

PMID- 9581506
TI  - Female physicians become mentors for Girl Scouts.

PMID- 9581507
TI  - Listeria monocytogenes rhomboencephalitis with cranial-nerve palsies: a case
      report.
AB  - Listeria monocytogenes rhomboencephalitis is an uncommon complication of L.
      monocytogenes meningitis. It presents in a typical biphasic pattern characterized
      by a non-specific prodromal period followed by any combination of asymmetrical,
      cranial-nerve palsies; cerebellar signs; hemiparesis or hypesthesia; and
      diminished consciousness. The survival rate is greater than 70% when appropriate
      antibiotic therapy is initiated early. However, approximately 60 percent of the
      survivors develop neurological sequelae. We present the case of a 33-year-old
      woman who developed L. monocytogenes meningitis with subsequent
      rhomboencephalitis and cranial-nerve palsie, and review the literature on this
      syndrome.

PMID- 9581508
TI  - Primary angioplasty in acute myocardial infarction: West Virginia University
      experience.
AB  - Primary angioplasty is a useful alternate treatment to open the occluded coronary
      arteries during the acute phase of a myocardial infarction associated with ST
      segment elevation. We describe our experience with 50 patients seen at West
      Virginia University Hospital in Morgantown over a period of one year.

PMID- 9581509
TI  - Axillary vein thrombosis during pregnancy in association with a lupus
      anticoagulant.
AB  - A 42-year-old multiparous pregnant woman presented with swelling and pain of the
      left arm at 34 weeks gestation. She had no discoloration of her arm nor a loss of
      radial pulse. Duplex scanning demonstrated a thrombosis in the axillary vein. She
      was found to have a positive circulating lupus anticoagulant. Intravenous heparin
      was administered and resulted in resolution of discomfort and swelling on day
      four of therapy. The patient was maintained on therapeutic doses of subcutaneous
      heparin until vaginal delivery at 39 weeks. Prenatal course was complicated by a
      resolving infection believed to be due to cat-scratch disease which produced a
      five centimeter cystic lesion in the left axillae which was removed in the first
      trimester. Titers for cat-scratch disease were positive for mother and infant at
      delivery but infant titers were negative at six weeks. Axillary vein thrombosis
      in pregnancy can be complicated by pulmonary embolism and should be treated by
      heparin.

PMID- 9581511
TI  - Adoption: from chaos to normalcy.
AB  - This article acknowledges the risk factors and psychological demands of the
      adopted child and adoptive parents. Despite many biologic and psychosocial
      obstacles, most adoptions are considered successful because most of the adopted
      children do not encounter long-term psychological difficulties.

PMID- 9581510
TI  - Bacteremia due to streptococcus zooepidemicus associated with an abdominal aortic
      aneurysm.
AB  - Group C streptococci are a common cause of infection in animals but a rare cause
      of infection in man. To our knowledge, the English literature contains only three
      cases of arteriosclerotic aneurysms of the abdominal aorta (AAA) secondarily
      infected with group C Beta-hemolytic Streptococci. Two cases did not survive in
      spite of adequate antibiotic therapy. One patient responded to aortic repair with
      a bifurcated woven dacron graft followed by four weeks of high-dose intravenous
      penicillin. This article describes our clinical experience with a patient who
      survived an atherosclerotic aneurysm of the abdominal aorta and S. zooepidemicus
      infection.

PMID- 9581512
TI  - Inhibition of eukaryote serine/threonine-specific protein kinases by piceatannol.
AB  - The protein tyrosine kinase (PTK) inhibitor piceatannol is also an inhibitor of
      the rat liver cyclic AMP-dependent protein kinase (PKA) catalytic subunit (cAK),
      rat brain Ca(2+)- and phospholipid-dependent protein kinase C (PKC), avian
      gizzard Ca(2+)-calmodulin-dependent myosin light chain kinae (MLCK), and of wheat
      embryo Ca(2+)-dependent protein kinase (CDPK) (IC50 values 3, 8, 12, and 19
      microM, respectively). However, a number of piceatannol-related compounds with
      fewer or no phenolic hydroxy substituents are inactive or very poor inhibitors of
      these serine/threonine protein kinases. Similarly, the PTK inhibitor ellagic acid
      is a potent inhibitor of cAK and of PKC (IC50 values 2 and 8 microM,
      respectively), whereas the non-phenolic perylene is ineffective as a protein
      kinase inhibitor. Ellagic acid is a competitive inhibitor of both cAK and of PKC
      but piceatannol inhibits these enzymes in a fashion that is competitive and non
      competitive, respectively. Interaction with calmodulin may contribute to the
      inhibition of MLCK and CDPK by piceatannol.

PMID- 9581513
TI  - Effects of compounds extracted from Tanacetum microphyllum on arachidonic acid
      metabolism in cellular systems.
AB  - In the present study, the effects of compounds extracted from Tanacetum
      microphyllum, four flavonoids and one sesquiterpene lactone, on arachidonic acid
      metabolism in cellular systems were examined. In the PGE2- and LTC4-release
      assay, most compounds did not exhibit any significant effect. Only
      hydroxyachillin, and the flavonoids centaureidin and 5,3'-dihydroxy-4'-methoxy-7
      methoxycarbonylflavonol showed a significant effect, although with less potency
      than the reference drugs, indomethacin and NDGA. However, all compounds inhibited
      the release of TXB2 from ionophore-stimulated human platelets. The action is more
      marked with the flavonoids santin and ermanin.

PMID- 9581514
TI  - Alpha-viniferin: a prostaglandin H2 synthase inhibitor from root of Carex
      humilis.
AB  - An inhibitor on cyclooxygenase activity of prostaglandin H2 synthase was purified
      from the root of Carex humilis Leyss (Cyperaceae) by a variety of column
      chromatographic methods. As a result of the structure analysis by FAB-mass, 1H
      NMR, and 13C-NMR spectral data, the active compound was identified as (+)-alpha
      viniferin, an oligomeric stilbene characterized originally from Caragana chamlagu
      Lamarck (Leguminosae). (+)-alpha-Viniferin exhibited a dose-dependent inhibition
      on cyclooxygenase activity, where 50% of inhibition (IC50) was shown at a final
      concentration of about 7 microM. Resveratrol, a putative building block of
      oligomeric stilbenes, also inhibited the cyclooxygenase activity. The inhibitory
      potency of (+)-alpha-viniferin was about 3- to 4-fold stronger than that of
      resveratrol on cyclooxygenase activity of prostaglandin H2 synthase partially
      purified from sheep seminal vesicles.

PMID- 9581515
TI  - Cytotoxic activity of labdane type diterpenes against human leukemic cell lines
      in vitro.
AB  - Nine labdane type diterpenes isolated from the plant Cistus creticus subsp.
      creticus and from the resin "Ladano" which is excreted on the surface of the
      leaves and stems of this plant, were examined for their in vitro cytotoxic
      activity against 14 human leukemic cell lines. Compound 1, (13E)-labd-13-ene-8
      alpha,15-diol, exhibited cytotoxic activity against 13 of the cell lines tested,
      while compound 2, (13E)-labd-7,13-dienol, was active only against HL60 cells.
      Further compound 1 was examined for its effect on the uptake of [3H]-thymidine as
      a marker of DNA synthesis.

PMID- 9581516
TI  - Anti-tumor effects of d-dicentrine from the root of Lindera megaphylla.
AB  - d-Dicentrine, a naturally occurring aporphine type isoquinoline alkaloid,
      isolated from the root of Lindera megaphylla Hemsl. (Lauraceae), was evaluated
      for its potential anti-cancer activity. We found d-dicentrine significantly
      inhibited the growth of human hepatoma cell line HuH-7 by delaying its doubling
      time in tissue culture. An in vitro colony forming assay showed that d-dicentrine
      decreased the colony formation efficiency in both hepatoma cell lines, HuH-7 and
      MS-G2, used in our study. Biosyntheses of the macromolecules DNA and RNA were
      also strongly inhibited. An MTT assay in 21 tumor cell lines also revealed that d
      dicentrine was most cytotoxic to esophageal carcinoma HCE-6, lymphoma cell lines
      Molt-4 and CESS, leukemia cell lines HL60 and K562, and hepatoma cell line MS-G2.
      An in vitro tumor growing assay in the Severe Combined immunodeficiency (SCID)
      mice showed that intraperitoneal injection of d-dicentrine at the dose of 100
      micrograms twice a week for 4 weeks significantly inhibited the tumor incidence
      of leukemia cell line K562 in SCID mice. All these data indicated that d
      dicentrine has potential anti-tumor applications.

PMID- 9581517
TI  - Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT
      1080 invasiveness in vitro.
AB  - We investigated the inhibitory effect of eggplant (Solanum melongena var.
      marunasu) extract on human fibrosarcoma HT-1080 cell invasion of reconstituted
      basement membrane [Matrigel (MG)]. We found that the effective component of the
      plant extract was delphinidin, a flavonoid pigment contained in the peel. The
      extract and delphinidin did not affect tumor cell adhesion to MG or haptotactic
      migration to MG. HT-1080 secretes matrix metalloproteinase(MMP)-2 and MMP-9,
      which degrade extracellular matrix as part of the invasive process. Delphinidin
      slightly inhibited the activity of MMPs, which may have been responsible, in
      part, for the inhibition of tumor cell invasiveness.

PMID- 9581518
TI  - Inhibitory effect of bupleuri radix saponins on adhesion of some solid tumor
      cells and relation to hemolytic action: screening of 232 herbal drugs for anti
      cell adhesion.
AB  - Anti-cell adhesive activity and hemolytic action of herbal drugs were
      investigated. Among 232 herbal drugs tested, six showed a remarkable anti-cell
      adhesive activity, and the extract from the roots of Bupleurum falcatum
      (Umbelliferae), the semen of Psorala corylifolia (Leguminosae), and the semen of
      Areca catechu (Palmae) showed an anti-cell adhesive action at non-cytotoxic
      concentrations. Saikosaponins-a, d and e, isolated from the roots of Bupleurum
      falcatum, exhibited a potent anti-cell adhesive activity and a strong hemolytic
      action. In a structure-activity relationship for both activities, it seems that a
      sugar moiety and an ether linkage between C-13 and C-28 are required for good
      bioactivities. In addition, saikosaponin d with a beta-hydroxy group at C-16 was
      more potent than saikosaponin a possessing an alpha-hydroxy group. Taken
      together, it is suggested that the mechanism for anti-cell adhesive activity of
      saikosaponin may resemble that for their hemolytic action.

PMID- 9581519
TI  - Hypotensive constituents from the pods of Moringa oleifera.
AB  - Hypotensive activity of the ethanolic and aqueous extracts of Moringa oleifera
      whole pods and their parts, namely, coat, pulp, and seed was investigated. The
      activity of the ethanolic extract of both the pods and the seeds was equivalent
      at the dose of 30 mg/kg. The ethyl acetate phase of the ethanolic extract of pods
      was found to be the most potent fraction at the same dose. Its bioassay-directed
      fractionation led to the isolation of thiocarbamate and isothiocyanate glycosides
      which were also the hypotensive principles of the pods as observed in case of
      Moringa leaves. Two new compounds, O-[2'-hydroxy-3'-(2"-heptenyloxy)]-propyl
      undecanoate (1) and O-ethyl-4-[(alpha-L-rhamnosyloxy)-benzyl] carbamate (2) along
      with the known substances methyl p-hydroxybenzoate (3) and beta-sitosterol have
      also been isolated in the present studies. The latter two compounds and p
      hydroxybenzaldehyde showed promising hypotensive activity. Structures of all
      these compounds have been deduced by spectroscopy and chemical reactions.

PMID- 9581520
TI  - The selective antianginal effect without changing blood pressure of
      butylidenephthalide in conscious rats.
AB  - Synthetic butylidenephthalide (Bdph), 60 mg/kg per os (p.o.) given 3 h prior to
      injection of pituitrin (4 U/kg, i.v.), significantly prevented T-wave lowering on
      lead II electrocardiograph in unanesthetized rats. The effective dose, 60 mg/kg,
      was about 1/56th of the median lethal dose (LD50, p.o.) in rats. However, Bdph
      (60 mg/kg, p.o.) did not affect systolic pressure and heart rate in
      unanesthetized rats. Therefore, Bdph, found in the rhizome of Ligusticum
      chuaxiong Hort. (L. wallichii Franch., Umbelliferae), appears to have selective
      antianginal effect without changing blood pressure and heart rate.

PMID- 9581521
TI  - Structure-hepatoprotective relationships study of soyasaponins I-IV having
      soyasapogenol B as aglycone.
AB  - As a part of our study on the leguminous plants, we investigated the constituents
      of the aerial parts of Glycine soya. We isolated and identified four known
      saponins, soyasaponins I, II, III, and IV which have the same aglycone,
      soyasapogenol B. As a part of our studies concerning hepatoprotective drugs, we
      also examined the hepatoprotective actions of these saponins towards
      immunologically induced liver injury on primary cultured rat hepatocytes. The
      action of soyasaponin II was almost comparable with that of soyasaponin I,
      whereas those of soyasaponin III and IV were more effective than soyasaponins I
      and II. This means that the disaccharide group shows greater action than the
      trisaccharide group. Furthermore, the saponin having a hexosyl unit shows a
      slightly greater action than that of the pentosyl unit in each disaccharide group
      or trisaccharide group. Structure-activity relationships suggest that the sugar
      moiety linked at C-3 may play an important role in hepatoprotective actions of
      soybean saponins.

PMID- 9581522
TI  - Antimalarial naphthoquinones from Nepenthes thorelii.
AB  - Roots of Nepenthes thorelii yielded plumbagin, 2-methylnaphthazarin, octadecyl
      caffeate, isoshinanolone, and droserone. In addition, seven derivatives were
      prepared from plumbagin. Each of these natural and semisynthetic compounds was
      evaluated for in vitro antimalarial potential.

PMID- 9581523
TI  - Angiotensin converting enzyme (ACE) inhibitors from Jasminum azoricum and
      Jasminum grandiflorum.
AB  - Bioactivity-guided fractionation of extracts of the aerial parts of Jasminum
      azoricum var. travancorense, using an in vitro ACE inhibition assay, led to
      isolation of three oligomeric, iridoid-type compounds, which were named sambacein
      I-III. Their structures are based on spectroscopic and chemical evidence.
      Similarly, fractionation of extracts of aerial parts of J. grandiflorum resulted
      in the isolation of the previously reported ACE inhibitor, oleacein. The IC50
      values of purified ACE inhibitors were 26-36 microM. Moreover, 2-(3,4
      dihydroxyphenyl)-ethanol, isoquercitrin and ursolic acid were isolated from J.
      grandiflorum. Sambaceins and oleacein are formed from genuine iridoid glucosides
      during processing of the plant material. NMR spectroscopy was used to measure the
      level of the ACE inhibitors in the traditional medicines prepared in Kerala from
      these Jasminum species.

PMID- 9581524
TI  - Generation and characterization of monoclonal antibodies against the
      pyrrolizidine alkaloid retrorsine.
AB  - Monoclonal antibodies against retrorsine were established using a retrorsine
      hemisuccinate::bovine-thyroglobuline conjugate as antigen for immunization. In
      competitive enzyme-linked immunoassays the specificity of the obtained antibodies
      was tested with 20 different pyrrolizidine alkaloids. Among these the alkaloids
      acetylgynuramine, gynuramine, integerrimine, neoplatyphylline, platyphylline,
      rosmarinine, senecionine, and seneciphylline were able to bind the antibody.
      There was no cross-reactivity with the alkaloids senkirkine, angeloyl
      heliotridine, heliotridine, axillarine, anacrotine, monocrotaline, madurensine,
      otosenine, retronecine, tussilagine, triangularine, and jacoline as well as with
      seneciphylline N-oxide. From this antigen spectrum it can be concluded that
      besides the necic structure itself the dominant and discriminative epitope
      consists of the exocyclic ethylidene group of the various diesters.

PMID- 9581525
TI  - Improved taxol yield in cell suspension culture of Taxus wallichiana (Himalayan
      yew)
AB  - Cell culture of Taxus wallichiana Zucc (= T. baccata ssp wallichiana Zucc. Pilg.)
      (Himalayan yew) has been established and taxol-producing cell lines selected by
      cell line cloning. Cell line NC110 derived from needle leaf of a 40-year-old tree
      growing in Darjeeling Himalayas produced 0.018% taxol in B5 basal medium
      supplemented with 2,4-D (2 mg/l), kinetin (0.5 mg/l), and casein hydrolysate
      (0.5%). This cell line has been maintained for over 2 years. Significant
      enhancement in the level of taxol (0.05%) was obtained in this cell line by
      supplementation of the basal medium with 5 mg/l of IAA-phenylalanine instead of
      2,4-D without adversely affecting cell growth. IAA-glycine also enhanced taxol
      level (0.03%) while IAA alone (1-10 mg/l) was ineffective in inducing taxol
      accumulation. Using three different cell lines with different taxol-producing
      capacities, it has been demonstrated that 2,4-D and IAA-phenylalanine when
      present alone favour growth and taxol production but when combined enhance
      biomass to a maximum (six-fold in NC110) without enhancing taxol accumulation,
      suggesting that a two-stage culture may be beneficial for optimising taxol
      accumulation in cell culture of T. wallichiana.

PMID- 9581526
TI  - Structures of the two saponins isolated from commercially available root extract
      of Primula sp.
AB  - The two main saponins of commercially available extract of Primula sp. were
      isolated by HPLC. Their structures were elucidated by spectroscopic methods as
      already known primulasaponin (1) and the new 3-O-?[alpha-rhamnopyranosyl-(1-->2)
      beta- galactopyranosyl-(1-->3)-[beta-xylopyranosyl-(1-->4)-beta-glucopyranosyl -
      (1-->2)]-beta-glucuronopyranosyl]?-protoprimulagenin A (2).

PMID- 9581527
TI  - Immunochemical distinction of Aloe vera, A. arborescens, and A. chinensis gels.
AB  - Verectin antiserum raised in white rabbits was immunoprecipitated with the Aloe
      vera nondialysable fraction. Analysis of the immunoprecipitation revealed that
      verectin accounted for about 1.25% of the total proteins in the nondialysable
      fraction of Aloe vera gel. The verectin antibody showed differential
      immunoreactivities against nondialysable fractions of A. arborescens, A.
      chinensis, and A. vera: 1) an immunopreciptin line was formed against the
      fraction of A. vera, but not against those of A. arborescens and A. chinensis gel
      in an Ouchterlony double immunodiffusion test and 2) an immunopositive band was
      detected in the A. vera and A. chinensis nondialysable fractions but not in that
      of A. arborescens in immunoblotting. These findings indicate that the verectin
      antibody can be used to distinguish Aloe materials.

PMID- 9581528
TI  - Xanthones with antimalarial activity from Garcinia dulcis.
AB  - Chromatographic separation of the EtOH extract of the bark of Garcinia dulcis
      (Guttiferae) furnished five xanthones, viz 1,7-dihydroxyxanthone (1), 12b-hydroxy
      des-D-garcigerrin A (2), 1-O-methylsymphoxanthone (3), symphoxanthone (4), and
      garciniaxanthone (5). These xanthones 1-5 showed inhibitory effects on the growth
      of Plasmodium falciparum with IC50 values of 0.96-3.88 micrograms/ml. In
      addition, revised 13C-NMR assignments of 3 and complete 13C-NMR assignments of 4
      were obtained through analysis of their COSY, NOESY, HMQC, and HMBC spectra.

PMID- 9581529
TI  - Inhibitory effects of hydroxystilbenes on cyclooxygenase from sheep seminal
      vesicles.

PMID- 9581530
TI  - New treatments for schizophrenia--Part II.

PMID- 9581531
TI  - Neuropsychological testing.

PMID- 9581532
TI  - Dissociated killers.

PMID- 9581533
TI  - Strokes and Alzheimer's disease.

PMID- 9581534
TI  - The imprint of a father.

PMID- 9581535
TI  - A protective factor.

PMID- 9581536
TI  - What are the new treatments for bipolar disorder?

PMID- 9581537
TI  - GLUT4 vesicle dynamics in living 3T3 L1 adipocytes visualized with green
      fluorescent protein.
AB  - Insulin stimulates glucose uptake into its target cells by a process which
      involves the translocation of the GLUT4 isoform of glucose transporter from an
      intracellular vesicular compartment(s) to the plasma membrane. The step(s) at
      which insulin acts in the vesicle trafficking pathway (e.g. vesicle movement or
      fusion with the plasma membrane) is not known. We expressed a green-fluorescent
      protein-GLUT4 (GFP-GLUT4) chimaera in 3T3 L1 adipocytes. The chimaera was
      expressed in vesicles located throughout the cytoplasm and also close to the
      plasma membrane. Insulin promoted a substantial translocation of GFP-GLUT4 to the
      plasma membrane. Time-lapse confocal microscopy demonstrated that the majority of
      GFP-GLUT4-containing vesicles in the basal state were relatively static, as if
      tethered (or attached) to an intracellular structure. A proportion (approx. 5%)
      of the vesicles spontaneously lost their tether, and were observed to move
      rapidly within the cell. Other vesicles appear to be tethered only on one edge
      and were observed in a rapid stretching motion. The data support a model in which
      GLUT4-containing vesicles are tightly tethered to an intracellular structure(s),
      and indicate that a primary site of insulin action must be to release these
      vesicles, allowing them to then translocate to and fuse with the plasma membrane.

PMID- 9581538
TI  - Cucurbitacins are insect steroid hormone antagonists acting at the ecdysteroid
      receptor.
AB  - Two triterpenoids, cucurbitacins B and D, have been isolated from seeds of Iberis
      umbellata (Cruciferae) and shown to be responsible for the antagonistic activity
      of a methanolic extract of this species in preventing the 20-hydroxyecdysone
      (20E)-induced morphological changes in the Drosophila melanogaster BII permanent
      cell line. With a 20E concentration of 50 nM, cucurbitacins B and D give 50%
      responses at 1.5 and 10 microM respectively. Both cucurbitacins are able to
      displace specifically bound radiolabelled 25-deoxy-20-hydroxyecdysone
      (ponasterone A) from a cell-free preparation of the BII cells containing
      ecdysteroid receptors. The Kd values for cucurbitacins B and D (5 and 50 microM
      respectively) are similar to the concentrations required to antagonize 20E
      activity with whole cells. Cucurbitacin B (cucB) prevents stimulation by 20E of
      an ecdysteroid-responsive reporter gene in a transfection assay. CucB also
      prevents the formation of the Drosophila ecdysteroid receptor/Ultraspiracle/20E
      complex with the hsp27 ecdysteroid response element as demonstrated by gel-shift
      assay. This is therefore the first definitive evidence for the existence of
      antagonists acting at the ecdysteroid receptor. Preliminary structure/activity
      studies indicate the importance of the Delta23-22-oxo functional grouping in the
      side chain for antagonistic activity. Hexanorcucurbitacin D, which lacks carbon
      atoms C-22 to C-27, is found to be a weak agonist rather than an antagonist.
      Moreover, the side chain analogue 5-methylhex-3-en-2-one possesses weak
      antagonistic activity.

PMID- 9581539
TI  - Cross-species characterization of the promoter region of the cystic fibrosis
      transmembrane conductance regulator gene reveals multiple levels of regulation.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) gene is highly
      conserved within vertebrate species. Its pattern of expression in vivo seems to
      be tightly regulated both developmentally and in a tissue-specific manner, but
      shows differences with species. To identify transcriptional regulatory elements
      in the CFTR promoter region, we have used a combined approach based both on the
      analysis of the chromatin structure in vivo in rat tissues and on evolutionary
      clues (i.e. phylogenetic footprinting). In CFTR-expressing tissues, 15 DNase I
      hypersensitive sites were identified within a 36 kb region encompassing exon 1.
      Eleven of them are clustered in a 3.5 kb region that exhibits eleven phylogenetic
      footprints observed when comparing sequences from eight mammalian species
      representing four orders (Primates, Artiodactylia, Lagomorpha and Rodentia).
      Comparison of the two sets of data allows the identification of two types of
      regulatory elements. Some are conserved between species, such as a non-consensus
      cAMP response element (CRE) and a PMA-responsive element (TRE) located
      respectively at positions -0.1 and -1.3 kb relative to ATG. Some are species
      specific elements such as a 300 bp purine.pyrimidine (Pu.Py) stretch that is
      present only in rodents. Analysis of protein/DNA interactions in vitro with rat
      tissue protein extracts on the conserved elements revealed that the TRE site
      binds a specific heterodimeric complex composed of Fra-2, Jun D and a protein
      immunologically related to Jun/CRE-binding protein in the duodenum, whereas the
      CRE-like site binds ATF-1 ubiquitously. Functional analysis in Caco-2 cells
      showed that the CRE-like site supports a high basal transcriptional activity but
      is not able by itself to induce a response to cAMP, whereas the TRE site acts as
      a weak transactivator stimulated by PMA. Lastly, we found that the rodent
      specific Pu.Py stretch confers nuclease S1 hypersensitivity under conditions of
      acidic pH and supercoiling. This indicates a non-B DNA conformation and thus
      reinforces the biological significance of non-random Pu.Py strand asymmetry in
      the regulation of transcription. Thus the tight transcriptional regulation of
      CFTR expression involves the combination of multiple regulatory elements that act
      in the chromatin environment in vivo. Some of them are conserved throughout
      evolution, such as the CRE-like element, which is clearly involved in the basal
      level of transcription; others are species-specific.

PMID- 9581540
TI  - Transforming growth factor beta1 attenuates ceramide-induced CPP32/Yama
      activation and apoptosis in human leukaemic HL-60 cells.
AB  - Ceramide, a product of sphingomyelin turnover, is a novel lipid second messenger
      that mediates important cellular functions including proliferation,
      differentiation and apoptosis. This study demonstrates that the CPP32/Yama
      protease was activated during apoptosis induced by the membrane-permeable second
      messenger C2-ceramide in HL-60 cells. We also found that the addition of a
      specific tetrapeptide inhibitor of CPP32/Yama, Ac-DEVD-CHO, provided an effective
      protection against ceramide-induced cell death. These results suggested that
      CPP32/Yama has a central role in ceramide-mediated apoptosis. Furthermore a wide
      variety of cytokines were examined for their effect on ceramide-induced
      apoptosis. Only transforming growth factor beta1 (TGF-beta1) (1 ng/ml) exerted
      significant prevention of apoptosis induced by C2-ceramide, or by
      sphingomyelinase (increases intracellular ceramide). Consistently, TGF-beta1
      abrogated the cleavage of poly(ADP-ribose) polymerase and the production of the
      CPP32/Yama active subunit, p17. However, TGF-beta1 treatment did not cause growth
      inhibition or alter the level of cyclin-dependent kinase inhibitor p27. It
      suggests that the preventive effect of TGF-beta1 is not mediated by growth
      arrest. Interestingly, we found that TGF-beta1 prevented the C2-ceramide-caused
      decrease of Bcl-2 protein. We thus propose that TGF-beta1 rescues ceramide
      induced cell death, possibly by maintaining the constant level of Bcl-2, thereby
      abolishing CPP32/Yama protease activation.

PMID- 9581541
TI  - alpha1-Adrenoceptor-mediated phosphorylation of myosin in rat-tail arterial
      smooth muscle.
AB  - The mechanism of alpha1-adrenoceptor-mediated contraction was investigated in
      helical strips of the rat-tail artery. Muscle strips with the endothelium removed
      contracted in response to the alpha1-adrenoceptor agonist cirazoline, with half
      maximal contraction at 0.23 microM. The contractile response to a submaximal
      concentration of cirazoline (0.3 microM) was biphasic, with a rapid phasic
      component peaking at approx. 30 s, followed by sustained tonic contraction.
      Phosphorylation of the 20 kDa light chain of myosin (LC20) in response to 0.3
      microM cirazoline was also biphasic and closely matched the time-course of
      contraction. Resting LC20 phosphorylation levels were 0.22+/-0.06 mol of Pi/mol
      of LC20 (n=3) and reached a maximum of 0.58+/-0.08 mol of Pi/mol of LC20 (n=3).
      Phosphopeptide mapping and phosphoamino acid analysis revealed that LC20
      phosphorylation occurred exclusively at serine-19. The sustained phase of
      contraction was eliminated by removal of extracellular Ca2+ and the phasic
      response was eliminated by depletion of endogenous Ca2+ stores. Both phases of
      the contractile response were restored by re-addition of Ca2+ to the bathing
      medium. LC20 phosphorylation and both phases of the contractile response to 0.3
      microM cirazoline were inhibited by the myosin light-chain kinase inhibitor ML-9
      (30 microM). Resting LC20 phosphorylation, however, was unaffected by ML-9.
      Finally, both phasic and tonic responses to 0.3 microM cirazoline were partially
      inhibited by chloroethylclonidine (50 microM), suggesting the involvement of both
      alpha1A and alpha1B adrenoceptors in these contractile responses.

PMID- 9581542
TI  - A mutant phosphofructokinase produces a futile cycle during gluconeogenesis in
      Escherichia coli.
AB  - Strains of Escherichia coli bearing different forms of phosphofructokinase were
      used to assess the occurrence of futile cycling in cell resuspensions supplied
      with glycerol as gluconeogenic carbon source. A model was used to simulate
      results of different kinds of experiments for different levels of futile cycle.
      The main predictions of the model were experimentally confirmed in a strain with
      a mutant phosphofructokinase-2 (phosphofructokinase-2*) which is not inhibited by
      MgATP. The intracellular fructose 1, 6-bisphosphate concentration reaches
      significantly higher levels in the mutant-bearing strain than in strains with
      either phosphofructokinase-1 or -2. Also, this strain showed a higher rate and
      level of in vivo radioactive labelling of fructose 1, 6-bisphosphate, from a
      trace of [U-14C]glucose supplied during gluconeogenesis, indicating higher kinase
      activity in these conditions. Cell resuspensions of the mutant-bearing strain
      produced higher levels of radioactively labelled CO2 when supplied with [U
      14C]glycerol as the only carbon source. Simultaneously, fewer glycerol carbons
      were incorporated into HClO4-insoluble macromolecules. Finally, radioactive CO2
      output was measured in resuspensions supplied with glycerol as the major carbon
      source with traces of either [1-14C]glucose or [6-14C]glucose. It was found that,
      whereas in the strains with either of the wild-type phosphofructokinase
      isoenzymes, radioactive CO2 output from [1-14C]glucose was higher than with [6
      14C]glucose, the reverse is found for the strain with phosphofructokinase-2*.
      This result also agrees with the corresponding prediction of the model. Using the
      radioactivity flux rates predicted by the model, an explanation linking the
      futile cycle to the differential labelling of CO2 is advanced. Finally, on the
      basis of these results it is proposed that strains bearing phosphofructokinase-2*
      sustain higher rates of futile cycling during gluconeogenesis than strains
      bearing either of the wild-type isoforms of phosphofructokinase. The kinetic
      equations and parameter values used for the model simulations are given in
      Supplementary Publication SUP 50183 (8 pages), which has been deposited at the
      British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23
      7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J.
      (1997) 321, 8.

PMID- 9581543
TI  - Mechanism of tubulin-colchicine recognition: a kinetic study of the binding of
      the colchicine analogues colchicide and isocolchicine.
AB  - Colchicide (IDE) is a colchicine (COL) analogue in which the C-10 methoxy group
      is replaced by a hydrogen atom. Its binding to tubulin is accompanied by a
      quenching of the protein fluorescence. The fluorescence decrease shows a
      monoexponential time dependence. The observed rate constant increases in a non
      linear way with the total concentration of IDE, allowing the determination of a
      binding constant for an initial binding site (K1=5300+/-300 M-1) and the rate
      constant for the subsequent isomerization (k2=0.071+/-0.002 s-1) at 25 degrees C.
      The rate constant, k-2, for the reversed isomerization can be determined by
      displacement experiments. Despite the minor alteration of the C-ring substituent,
      the kinetic and thermodynamic parameters of binding are substantially different
      from those of COL itself, for both steps. In isocolchicine (ISO) the carbonyl
      oxygen atom and the methoxy groups of the C-ring have been interchanged. Its
      binding to tubulin only results in small fluorescence and absorbance changes.
      Therefore competition experiments with MTC [2-methoxy-5-(2',3',4'
      trimethoxyphenyl)-2,4, 6-cycloheptatrien-1-one] were performed. ISO competes
      rapidly and with low affinity with MTC. Fluorimetric titrations of tubulin with
      MDL (MDL 27048 or trans-1-(2,5 dimethoxyphenyl)-3-[4-(dimethylamino)phenyl]-2
      methyl-2-propen-1 -one) in the presence and absence of ISO give evidence for the
      existence of a second, slow-reacting low-affinity site for ISO that is not
      accessible to MTC or MDL. The relevance of these results for the recognition of
      COL is analysed.

PMID- 9581544
TI  - Identification of a key regulatory element for the basal activity of the human
      insulin-like growth factor II gene promoter P3.
AB  - Transcription of the human insulin-like growth factor II (IGF-II) gene is under
      the control of four promoters (P1-P4) that are differentially active during
      growth and development. Promoter 3 (P3) is the most active promoter during fetal
      development as well as in most adult tissues. P3 is also the most active promoter
      in tumour tissues and cell lines expressing IGF-II. Transient transfections of
      HeLa and Hep3B cells with truncated promoter constructs revealed that the region
      between -289 and -183 relative to the transcription start site supports basal
      promoter activity in both cell lines. Footprint experiments showed that the
      region between positions -192 and -172 (P3-4) is the only element bound by
      nuclear proteins. P3-4 is bound by five proteins, of which three proteins
      (proteins 3, 4 and 5) bind specifically and are expressed at the same levels in
      HeLa and Hep3B cells. Electrophoretic mobility shift assays and differential
      footprint experiments revealed the presence of two protein-binding regions within
      the P3-4 element. Proteins 4 and 5 bind box A (-193 to -188), whereas box B (-183
      to -172) is bound by protein 3. From transcription experiments in vitro it can be
      concluded that Box A is essential for P3 activity. Box A is part of a region 11
      dG residues long and is protected by proteins 4 and 5 that bind a contiguous set
      of six dG residues. DNA-binding of proteins 4 and 5 to box A requires the
      presence of Zn2+ ions. Thus structural and functional analysis reveals that the
      P3-4 element is a key regulatory element of P3 that contains two separate binding
      sites for proteins essential for the basal activity of IGF-II P3.

PMID- 9581545
TI  - Xyloglucan undergoes interpolymeric transglycosylation during binding to the
      plant cell wall in vivo: evidence from 13C/3H dual labelling and isopycnic
      centrifugation in caesium trifluoroacetate.
AB  - Xyloglucan from the walls of Rosa cells that had been cultured on [12C]- or [13C]
      glucose formed bands in caesium trifluoroacetate with mean buoyant densities of
      1.575 or 1.616 g/ml respectively. Incubation of a mixture of [13C,3H]xyloglucan
      and [12C,1H]xyloglucan in the presence of xyloglucan endotransglycosylase (XET)
      activity caused the mean buoyant density of the radioactive material to decrease,
      indicating that interpolymeric transglycosylation could be detected in vitro. We
      used two 13C/3H-dual-labelling protocols to look for interpolymeric
      transglycosylation in vivo. In protocol A, [13C]glucose-grown Rosa cells were
      transferred into [12C]glucose medium 6 h after a approximately 2 h pulse of l-[1
      3H]arabinose (which radiolabels the xylose residues of xyloglucan). The mean
      buoyant density of the wall-bound [3H]xyloglucan decreased during the following 7
      days in culture. This indicates that, during or after the wall-binding of newly
      synthesized [12C,1H]xyloglucan, it became covalently attached to previously wall
      bound [13C, 3H]xyloglucan. In protocol B, [12C]glycerol- or [12C]glucose-grown
      Rosa cells were transferred into [13C]glucose medium, 20 or 60 min before a
      approximately 2 h pulse of [3H]arabinose. The buoyant density of the earliest
      wall-bound [3H]xyloglucan showed that it had a 12C/13C ratio of approximately
      1:1. This indicates that, during (or, implausibly, before) wall-binding, the
      newly synthesized [13C, 3H]xyloglucan became covalently attached to previously
      synthesized [12C]xyloglucan. During the following 7 days in culture, the mean
      buoyant density of the [3H]xyloglucan increased, showing that later-synthesized
      [13C,1H]xyloglucan can be covalently attached to previously wall-bound
      [12C,13C,3H]xyloglucan. The only known mechanism by which segments of xyloglucans
      could become covalently attached to each other in the cell wall is by
      interpolymeric transglycosylation catalysed by XET. We conclude that XET
      catalysed interpolymeric transglycosylation accompanies, and probably causes, the
      integration of newly secreted xyloglucan into the cell-wall architecture.

PMID- 9581547
TI  - Allosteric communication in mammalian muscle aldolase.
AB  - Mixed disulphide formation in the presence of oxidized glutathione reversibly
      inactivates rabbit skeletal muscle aldolase. Inactivation is allosteric,
      preferentially modifying Cys-72 on the surface of the aldolase homotetramer
      distant from active-site locations and subunit interfaces. Ion-exchange
      chromatography fractionates partly inactivated aldolase into three distinct
      enzymic species: unmodified enzyme, inactive fully modified enzyme corresponding
      to one thiol reacted per subunit, and inactive singly modified enzyme in which
      only one thiol has reacted. Acid-precipitable enzymic intermediates formed in the
      presence of substrate, D-fructose 1,6-bisphosphate, and product, dihydroxyacetone
      phosphate, indicates that active site binding is unaffected upon modification.
      The absence of enamine carbanion formation in the presence of substrate but not
      product is consistent with mixed disulphide formation's blocking -C-C- cleavage
      and/or subsequent D-glyceraldehyde 3-phosphate release. Inactivation upon single
      subunit modification and substrate protection against modification denotes that
      the blocked step is associated with a long-range conformational transition
      involving highly co-operative subunit behaviour.

PMID- 9581546
TI  - Suppression of smooth-muscle alpha-actin expression by platelet-derived growth
      factor in vascular smooth-muscle cells involves Ras and cytosolic phospholipase
      A2.
AB  - Platelet-derived growth factor (PDGF), which is a potent mitogen for vascular
      smooth-muscle cells (VSMC), also inhibits the expression of specific smooth
      muscle proteins, including smooth-muscle alpha-actin (SM-alpha-actin), in these
      cells. The goal of this study was to identify signalling pathways mediating these
      distinct effects. In rat aortic VSMC, PDGF caused a rapid activation of Ras and
      Raf, leading to the activation of mitogen-activated protein kinases (ERKs). Cells
      stably transfected with constitutively active Ras (H-Ras) expressed low levels of
      SM-alpha-actin protein. Arginine vasopressin, which stimulated SM-alpha-actin
      promoter activity in wild-type cells or controls (Neo; transfected with a plasmid
      lacking an insert), failed to do so in cells transiently expressing H-Ras. The
      effects of Ras on suppression of SM-alpha-actin expression were not mediated by
      the Raf/ERK pathway, since cells stably expressing constitutively active Raf (BxB
      Raf) had normal levels of SM-alpha-actin protein, and stimulation of SM-alpha
      actin promoter activity by vasopressin was unaffected in cells transiently
      expressing BxB-Raf. Furthermore a specific inhibitor of ERK activation had no
      effect on SM-alpha-actin expression. Exposure of wild-type VSMC to PDGF, or
      stable expression of Ras but not Raf, also resulted in constitutive increases in
      prostaglandin E2 production and cytosolic phospholipase A2 (cPLA2) activity,
      which was mediated by an increased expression of cPLA2 protein. Transient
      expression of cPLA2 in wild-type VSMC inhibited the stimulation of SM-alpha-actin
      promoter activity by vasopressin. These results suggest that PDGF-induced
      inhibition of SM-alpha-actin expression is mediated through a Ras-dependent/Raf
      independent pathway involving the induction of cPLA2 and eicosanoid production.

PMID- 9581548
TI  - Glutathione S-transferases act as isomerases in isomerization of 13-cis-retinoic
      acid to all-trans-retinoic acid in vitro.
AB  - A discovery that rapid enzymic isomerization of 13-cis-retinoic acid (13-cRA) to
      all-trans-retinoic acid (t-RA) can be catalysed by purified hepatic glutathione S
      transferases (GSTs; EC 2.5.1.18) from rat is now reported. Rates of cis-trans
      isomerization were determined quantitatively by HPLC. GST-catalysed reactions
      reached equilibrium rapidly, in marked contrast with uncatalysed or GSH-catalysed
      isomerizations. The GST-catalysed reaction exhibited substrate saturation
      kinetics with a Km of approx. 8 microM. The maximal velocity of the reaction and
      the catalytic efficiency of GSTs were determined. The initial rate of the
      reaction increased linearly as a function of enzyme concentration. Catalysis by
      GSTs was independent of the presence of GSH, indicating that GSTs act as GSH
      independent isomerases as well as transferases. Incubation with guanidine (7-8 M)
      or heat-inactivation of GSTs (100 degrees C for 3 min) decreased isomerase
      activities by approx. 50% and 75% respectively. The same heat treatment did not
      significantly inhibit isomerization catalysed by GSH and apoferritin, indicating
      that the observed decrease in isomerase activity by heat inactivation was not
      primarily due to oxidation of protein thiol groups in the GSTs. The specific
      activity of GSTs was approx. 23- and 340-fold those of GSH and apoferritin
      respectively when comparisons were made on the basis of free thiol
      concentrations, indicating that free thiol in GSTs cannot account for the
      majority of observed isomerase activities and suggesting that specific
      conformations of GSTs are important for such activities. Complete inhibition of
      the reaction by low concentrations of N-ethylmaleimide (10 microM) demonstrated
      that intact protein thiols are required for the isomerase activities of GSTs.

PMID- 9581549
TI  - A novel region of the alpha4 integrin subunit with a modulatory role in VLA-4
      mediated cell adhesion to fibronectin.
AB  - The integrin VLA-4 (alpha4 beta1) is a receptor for fibronectin and vascular cell
      adhesion molecule 1 (VCAM-1). Four functionally different epitopes, designated A,
      B1, B2 and C, have previously been defined on the alpha4 subunit. Using K562
      alpha4 mutant transfectants we found that alpha4 amino acids Tyr151, Gln152,
      Asp153, Tyr154 and Val155 are important for the structure of the epitope B2.
      Mutations at alpha4 Gln152 substantially impaired the transfectant adhesion to a
      CS-1-containing fragment of fibronectin (FN-H89), whereas this adhesion was not
      affected on the other alpha4 mutant transfectants. None of the alpha4 mutations
      significantly altered the adhesion of the different alpha4 transfectants to VCAM
      1. In addition, we have identified residues Gln152, Asp153 and Tyr154 as part of
      the alpha4 epitope B2 involved in homotypic cell aggregation. The decrease in
      adhesion to FN-H89 shown by Gln152 alpha4 mutant transfectants was the result of
      an inefficient binding of FN-H89 by VLA-4 mutated at this residue. Also, mutant
      VLA-4 displayed an altered reactivity with HUTS-21, an anti-beta1 monoclonal
      antibody that reacts with functionally active VLA integrins. Adhesion to FN-H89
      was not restored unless stimuli that increase the ligand-binding affinity of VLA
      heterodimers were added, suggesting that cell adhesion was affected in the
      initial phases. These results indicate that alpha4 Gln152 modulates cell adhesion
      to FN-H89 by playing important roles in the maintenance and/or the acquisition of
      an active state of VLA-4, an integrin that is normally expressed on the cell
      surface in a range of multiple activation states. The location of the alpha4
      Gln152 residue on a loop of the upper surface of the proposed beta-propeller
      structure suggests a close association with potential ligand-binding sites.

PMID- 9581551
TI  - Identification of cytoskeleton-associated proteins in isolated rat liver
      endosomes.
AB  - The polypeptides of three highly purified endosomal fractions isolated from the
      livers of oestradiol-treated rats were analysed by Western blotting, and the
      amount and distribution of intrinsic and cytoskeletal-associated proteins were
      quantified and studied. The 'late' endosomes [multivesicular bodies (MVBs)] had
      the lowest content of cytoskeletal-associated proteins, the most significant
      being the presence of 25% of the total dynein found in endosomes. The 'early'
      endosome [compartment of uncoupling receptors and ligands (CURL)] fraction
      contained kinesin (40% of the total in endosomes), dynein (23%), actin (15%) and
      tubulin (10%). The receptor-recycling compartment (RRC), also demonstrated to be
      involved in transcytosis, contained the largest number and enrichment of
      cytoskeletal proteins: actin (84% of the total in endosomes), alpha-actinin
      (90%), dynein (52%), tubulin (91%) and kinesin (45%). We also analysed and
      compared the presence of different endosomal markers such as Rab4, Rab5 and
      cellubrevin (vesicle soluble NSF attachment protein receptor) in CURL (41%, 15%
      and 60%) and in RRC (44%, 75% and 30% respectively). Finally, the expression of
      annexins I, II, IV and VI was studied: annexin I was equally distributed between
      MVBs and CURL; annexin II was highly enriched in RRC (95%), annexin IV was
      equally distributed between CURL and RRC, and annexin VI was enriched in CURL
      (57%). The results indicate that isolated rat liver endosomes contain all the
      required molecular machinery for the achievement of their role in intracellular
      trafficking.

PMID- 9581550
TI  - Relative contributions of Na+-dependent phosphate co-transporters to phosphate
      transport in mouse kidney: RNase H-mediated hybrid depletion analysis.
AB  - Reabsorption of Pi in the proximal tubule of the kidney is an important
      determinant of Pi homoeostasis. At least three types (types I-III) of high
      affinity Na+-dependent Pi co-transporters have been identified in mammalian
      kidneys. The relative roles of these three types of Na+/Pi co-transporters in Pi
      transport in mouse kidney cortex have now been investigated by RNase H-mediated
      hybrid depletion. Whereas isolated brush-border membrane vesicles showed the
      presence of two kinetically distinct Na+/Pi co-transport systems (high Km-low
      Vmax and low Km-high Vmax), Xenopus oocytes, microinjected with polyadenylated
      [poly(A)+] RNA from mouse kidney cortex, showed only the high-affinity Pi uptake
      system. Kidney poly(A)+ RNA was incubated in vitro with antisense
      oligonucleotides corresponding to Npt-1 (type I), NaPi -7 (type II) or Glvr-1
      (type III) Na+/Pi co-transporter mRNAs, and then with RNase H. Injection of such
      treated RNA preparations into Xenopus oocytes revealed that an NaPi-7 antisense
      oligonucleotide that resulted in complete degradation of NaPi-7 mRNA (as revealed
      by Northern blot analysis), also induced complete inhibition of Pi uptake.
      Degradation of Npt-1 or Glvr-1 mRNAs induced by corresponding antisense
      oligonucleotides had no effect on Pi transport, which was subsequently measured
      in oocytes. These results indicate that the type II Na+/Pi co-transporter NaPi-7
      mediated most Na+-dependent Pi transport in mouse kidney cortex.

PMID- 9581553
TI  - Expression levels of functional folate receptors alpha and beta are related to
      the number of N-glycosylated sites.
AB  - In a previous study with inhibitors of N-glycosylation, it was proposed that core
      glycosylation of the folate receptor (FR) is required for the proper folding of
      the protein [Luhrs (1991) Blood 77, 1171-1180]. The human FR isoforms type alpha
      and type beta have three and two candidate sites for N-glycosylation
      respectively, only one of which is conserved. The significance of N-glycosylation
      at each of these loci in the expression and function of FR was examined by
      eliminating the sites both individually and in combination by introducing Asn-
      >Gln substitutions. Translation experiments in vitro showed that the mutations
      did not alter the synthetic rates of the polypeptides. The recombinant proteins
      were expressed in human 293 fibroblasts. Treatment with N-glycanase and analysis
      by Western blotting of the wild-type and mutant proteins revealed that all of the
      candidate sites in both FR-alpha and FR-beta are glycosylated. When all of the N
      glycosylation sites were abolished, 2% and 8% of FR-alpha and FR-beta
      respectively were expressed on the cell surface compared with the corresponding
      wild-type proteins; the residual FR polypeptides in the cell lysates were unable
      to bind [3H]folic acid. In both the proteins, the inclusion of each additional N
      glycosylation site partly contributed to restoration of cell surface [3H]folic
      acid binding and receptor-mediated folate transport. Further, in FR-beta the
      introduction of an additional unnatural site of N-glycosylation resulted in the
      enhancement of the expression of the cell surface receptor compared with the wild
      type protein. The results indicate that the total mass of N-glycosylation, not a
      specific locus of the modification, is critical for the efficient folding and
      optimal expression of functional FR-alpha and FR-beta.

PMID- 9581552
TI  - Tetramerization domain of human butyrylcholinesterase is at the C-terminus.
AB  - Butyrylcholinesterase (BChE) in human serum consists predominantly of tetramers.
      Recombinant BChE, however, expressed in Chinese hamster ovary (CHO) cells,
      consists of approx. 55% dimers, 10-30% tetramers and 15-40% monomers. To
      determine the origin of the monomer species we added the FLAG epitope (epitope
      tag, amino acid sequence DYKDDDDK) to the C-terminus of the enzyme, and expressed
      BChE-FLAG in CHO cells. We found that secreted, active monomers had lost their
      FLAG epitope, suggesting that the monomers were made by proteolysis of dimers or
      tetramers at the C-terminus. To estimate the number of amino acids that could be
      deleted from the C-terminus without losing BChE activity, we expressed deletion
      mutants. We found that deletion of up to 50 amino acids from the C-terminus
      yielded active monomers, but that deletion of 51 amino acids destroyed BChE
      activity and caused the inactive protein to remain within the cell. Deletion of
      eight or more amino acids from the N-terminus also resulted in inactive protein
      that remained inside the cell. Monomeric BChE had wild-type Km and kcat values (8
      microM and 24000 min-1 for butyrylthiocholine) and showed substrate activation.
      The Cys-571-->Ala mutant, though incapable of forming the interchain disulphide
      bond, had nearly the same amount of tetrameric BChE as recombinant wild-type
      BChE. These results support the conclusion that the tetramerization domain of
      BChE is at the C-terminus, within the terminal 50 amino acids, and that the
      interchain disulphide bond is not essential for tetramerization. Molecular
      modelling suggested that the tetramerization domain was a four-helix bundle,
      stabilized by interactions of seven conserved aromatic amino acids.

PMID- 9581554
TI  - 14-3-3 proteins interact with the insulin-like growth factor receptor but not the
      insulin receptor.
AB  - We have used a yeast two-hybrid system to identify proteins which bind to the
      cytosolic portion of the type 1 insulin-like growth factor (IGF) receptor (IGFIR)
      but not the insulin receptor (IR). This analysis identified 14-3-3beta and zeta
      proteins. 14-3-3beta also binds to the IGFIR but not the IR in vitro and 14-3-3
      IGFIR complexes are present in insect cells overexpressing the IGFIR cytoplasmic
      domain. 14-3-3 proteins are substrates of the IGFIR in the yeast system and in
      vitro. The interaction of 14-3-3 with the IGFIR requires receptor-kinase activity
      and maps to the C-terminus of the receptor, but does not depend on tyrosine
      residues in this or the juxtamembrane regions. Instead, the binding maps to
      serine residue 1283 and requires phosphorylation of this residue. 14-3-3 proteins
      are phosphoserine-binding proteins which have been shown to interact directly
      with components of the mitogenic and apoptotic signalling pathways, suggesting
      that they participate in growth regulation. Our findings suggest that 14-3-3
      proteins may play a role in IGFIR signal transduction and may contribute to the
      differences in IGF and IR signalling capabilities.

PMID- 9581555
TI  - Human and rat testis express two mRNA species encoding variants of NRD
      convertase, a metalloendopeptidase of the insulinase family.
AB  - Rat testis NRD convertase (EC 3.4.24.61) is a Zn2+-dependent endopeptidase that
      cleaves, in vitro, peptide substrates at the N-terminus of Arg residues in
      dibasic sites. This putative processing enzyme of the insulinase family of
      metallopeptidases exhibits a significant degree of similarity to insulinase and
      two yeast processing enzymes, Axl1 and Ste23. We report the cloning of two human
      testis cDNA species encoding isoforms of NRD convertase, hNRD1 and hNRD2. Whereas
      the hNRD1 transcript (3.7 kb) is equivalent to the previously characterized rat
      cDNA (rNRD1), hNRD2 and rNRD2 are 3.9 kb novel forms containing a nucleotide
      insertion encoding a 68-residue segment. This motif, which is inserted N-terminal
      of the Zn2+-binding site, HXXEH, is contained within the most conserved region
      among the insulinase family members. Analysis of the deduced primary sequences
      revealed 92% identity between rat and human orthologues. The human gene encoding
      NRD convertase was localized to chromosome 1p32.1-p32.2. Whereas NRD convertase
      is mostly expressed in testis and in 24 cell lines, low mRNA levels were detected
      in most of the 27 other tissues tested.

PMID- 9581556
TI  - ATP stimulates lysosomal sulphate transport at neutral pH: evidence for
      phosphorylation of the lysosomal sulphate carrier.
AB  - ATP markedly stimulated sulphate uptake by rat liver lysosomes that had been
      treated with N-ethylmaleimide to block the effects of the lysosomal proton
      translocating ATPase (H+-ATPase). Maximal stimulation required millimolar
      concentrations of ATP and neutral buffer pH. ATP-stimulated transport exhibited
      saturation kinetics with a Km of 175 microM, identical with the Km for lysosomal
      sulphate uptake at pH 5.0, a process that does not require ATP. The requirement
      for ATP was specific: other nucleotides such as AMP, ADP, CTP, GTP, ITP and UTP
      failed to stimulate transport. Adenosine 5'-[beta,gamma-imido]triphosphate, the
      non-hydrolysable analogue of ATP, also failed to stimulate sulphate uptake,
      suggesting a requirement for ATP hydrolysis. Lysosomal pH, membrane potential and
      glucose transport were unchanged by the presence of ATP under the experimental
      conditions, consistent with a direct effect of ATP on the sulphate transporter.
      Exposure of lysosomes to protein kinase A and protein kinase C inhibitors did not
      alter the stimulation of sulphate transport by ATP. The lysosomal sulphate
      transport protein might be subject to regulation by a phosphorylation pathway
      that is not dependent on protein kinase A or protein kinase C.

PMID- 9581557
TI  - Mapping the binding site of thymosin beta4 on actin by competition with G-actin
      binding proteins indicates negative co-operativity between binding sites located
      on opposite subdomains of actin.
AB  - The beta-thymosins are small monomeric (G-)actin-binding proteins of 5 kDa that
      are supposed to act intracellularly as actin-sequestering factors stabilizing the
      cytoplasmic monomeric pool of actin. The binding region of thymosin beta4 was
      determined by analysing the binding of thymosin beta4 to actin complexed with
      DNase I, gelsolin or gelsolin segment 1. Binding was analysed by determining the
      increase in the critical concentration of actin polymerization by native gel
      electrophoresis or chemical cross-linking. The formation of a ternary complex
      including thymosin beta4 should indicate that the actin-binding proteins attach
      to different sites on actin. Competition would be indicative of binding to
      identical or overlapping sites on actin or of a negative co-operative linkage
      between the two binding sites. Competition of thymosin beta4 for actin binding
      was observed in the presence of intact gelsolin or the N-terminal gelsolin
      fragment, segment 1, indicating that thymosin beta4 binds to a site close to or
      identical with the gelsolin segment 1-binding site. The ternary complex of actin
      DNase I-thymosin beta4 was obtained only when using the chemically cross-linked
      actin-thymosin beta4 complex, indicating that thymosin beta4 is dissociated by
      the binding of DNase I to actin. It is suggested that the dissociation of
      thymosin beta4 by DNase I binding to actin is caused by negative co-operativity
      between their spatially separated binding sites on actin. A similar negative co
      operativity was observed between DNase I and gelsolin segment 1 binding to actin.
      The results therefore indicate that the respective binding sites for DNase I and
      segment 1 on subdomains 1 and 2 of actin are linked in a negative co-operative
      manner.

PMID- 9581558
TI  - Uncoupling of Ca2+ transport ATPase in muscle and blood platelets by
      diacylglycerol analogues and cyclosporin A antagonism.
AB  - The possibility that diacylglycerol analogues might have a wider spectrum of
      intracellular targets than the well-known protein kinase C was investigated with
      vesicles containing the Ca2+-ATPase derived from the dense tubular system in
      platelets and from the sarcoplasmic reticulum of skeletal muscle. The
      diacylglycerol analogues PMA and 1-oleoyl-2-acetyl-rac-glycerol (OAG) inhibited
      Ca2+ accumulation by these vesicles, an effect that was antagonized by
      cyclosporin A. The inhibitory activity of PMA and OAG resulted from the
      uncoupling of the Ca2+-ATPase, characterized by a pronounced inhibition of Ca2+
      uptake accompanied by a discrete decrease in ATPase activity and by the
      inhibition of the enzyme's phosphorylation by Pi, leading to both a decrease in
      ATP synthesis and an enhancement of Ca2+ efflux. The inhibition of Ca2+ uptake by
      PMA was found to decrease as the Ca2+ concentration in the medium was raised from
      0.1 to 10.0 microM. This was observed with muscle, but not with platelet
      vesicles. In contrast, the ability of cyclosporin A to antagonize the inhibition
      of Ca2+ uptake by PMA also increased when the Ca2+ concentration in the medium
      was raised from 0.1 to 10.0 microM, but this was observed with both muscle and
      platelet vesicles. The fact that phospholipase C activity and products from the
      inositol metabolism have been described as localized in regions of the
      sarcoplasmic reticulum where Ca2+-ATPase and Ca2+ channels are found suggests a
      possible physiological role for these products in the regulation of cytosolic
      Ca2+ levels.

PMID- 9581559
TI  - Enhanced bradykinin-stimulated phospholipase C activity in murine embryonic stem
      cells lacking the G-protein alphaq-subunit.
AB  - The gene coding for the G-protein alphaq subunit was interrupted by homologous
      recombination in murine embryonic stem cells (alphaq-null ES cells) as detected
      by Southern analysis and reverse-transcriptase PCR. The bradykinin (BK) B2
      receptor was stably transfected into wild-type (WT) alphai-2-null and alphaq-null
      ES cells. The B2 receptor bound BK with high affinity and mobilized Ca2+. BK also
      activated phospholipase C (PLC), as determined by total inositol phosphate (IP)
      accumulation in a Bordetella pertussis toxin- and genistein-insensitive manner.
      In WT and alphai-2-null ES cells, BK increased IP levels approx. 4-fold above
      baseline. Most interestingly, in alphaq-null ES cells, BK increased IP
      accumulation approx. 9-fold above baseline. Re-expression of alphaq in alphaq
      null ES cells resulted in normalization of the BK-stimulated IP accumulation (4
      fold above baseline). These results suggest that the B2 receptor activates PLC
      through more than one member of the Gq family. Additionally, the absence of
      alphaq alters the kinetics of IP generation, which may reflect intrinsic
      characteristics of individual members of the Gq family or a decreased
      susceptibility to heterologous regulation in the alphaq-null ES cells, thus
      allowing for a more sustained generation of IP.

PMID- 9581560
TI  - The 46 kDa mannose-6-phosphate receptor contains a signal for basolateral sorting
      within the 19 juxtamembrane cytosolic residues.
AB  - The cytosolic domain of the 46 kDa mannose-6-phosphate receptor (MPR 46) contains
      a signal that mediates sorting of the receptor and of a reporter protein to the
      basolateral surface domain of Madin-Darby canine kidney cells. Progressive
      truncation of the 67 cytosolic residues indicated that the 19 juxtamembrane
      residues are sufficient for basolateral sorting. Alanine/glycine-scanning
      mutagenesis identified Glu-11 and Ala-17 as the critical residues between
      residues 7 and 19. Glu-11 is also of critical importance for the one of the three
      internalization signals in the cytosolic tail of the receptor [Denzer, Weber,
      Hille-Rehfeld, von Figura and Pohlmann (1997) Biochem. J. 326, 497-505]. Although
      overlapping, the signals for basolateral sorting and internalization depend on
      different residues. The basolateral sorting signal of MPR 46 is distinct from
      tyrosine- or dileucine-based basolateral sorting signals and also lacks
      similarity to the few other basolateral signals that do not fall into these two
      classes.

PMID- 9581561
TI  - Differential regulation of nitric oxide synthase mRNA expression by
      lipopolysaccharide and pro-inflammatory cytokines in fetal hepatocytes treated
      with cycloheximide.
AB  - The effect of cycloheximide (CHX) on the mRNA expression of the cytokine
      inducible, calcium-independent nitric oxide synthase (iNOS) was investigated in
      fetal hepatocytes stimulated with lipopolysaccharide (LPS) or pro-inflammatory
      cytokines. In the presence of CHX the LPS-dependent iNOS mRNA levels were
      reduced, whereas the response to pro-inflammatory cytokines was enhanced. Because
      iNOS transcription is highly dependent on the activation of nuclear factor kappaB
      (NF-kappaB), this factor was evaluated by electrophoretic mobility shift assays,
      and a close correlation between NF-kappaB activity and iNOS mRNA levels was
      observed. CHX itself potentiated the degradation of the IkappaB alpha and IkappaB
      beta inhibitory subunits (IkappaB is inhibitory kappaB) of the NF-kappaB complex,
      and therefore the loss of LPS-dependent iNOS mRNA expression cannot be attributed
      to a blockage in the activation of NF-kappaB. These results suggest the existence
      of a CHX-sensitive pathway in the expression of iNOS mediated by LPS, a mechanism
      that is not involved in the response to pro-inflammatory cytokines.

PMID- 9581562
TI  - Staphylococcus aureus causing osteomyelitis binds to a nonapeptide sequence in
      bone sialoprotein.
AB  - Bone sialoprotein is a glycoprotein of the bone and dentine extracellular matrix.
      This protein consists of 320 amino acids, of which 25% are glutamic and aspartic
      acid residues. Sialic acid, containing oligosaccharides and tyrosine sulphate
      residues, supplies additional polyanionic properties. Staphylococcal cells,
      isolated from patients suffering from infection of bone tissue, bind the bone
      derived sialoprotein, an interaction which is specifically inhibited by the
      recombinant bone sialoprotein core protein. We have previously shown that the 150
      N-terminal amino acid residues of bone sialoprotein are responsible for the
      binding to staphylococcal cells. By using recombinant deleted variants of bone
      sialoprotein and synthetic peptides, we have now localized the staphylococcal
      binding site to less than 10 residues within the N-terminal part of the protein.

PMID- 9581563
TI  - Immortalized, cloned mouse chondrocytic cells (MC615) produce three different
      matrix proteoglycans with core-protein-specific chondroitin/dermatan sulphate
      structures.
AB  - Cloned immortalized MC615 mouse chondrocytic cells were used to examine their
      capability to produce multiple types of matrix proteoglycans. Immunofluorescence
      staining indicated a uniform expression of aggrecan, biglycan and decorin by all
      cells. After culture with [35S]sulphate, proteo[35S]glycans secreted by the cells
      were found to elute in two peaks from a Sepharose CL-4B column. The first peak,
      at the void volume of the column, contained a large proteoglycan with an
      estimated average hydrodynamic mass of 10(3) kDa. The glycosaminoglycan chains of
      this proteoglycan had an average hydrodynamic size of 17 kDa, estimated by
      Sepharose CL-6B chromatography, indicating the presence of 30-70
      glycosaminoglycan chains per core protein, which was consistent with the
      characteristics of aggrecan. Biglycan and decorin were immunoisolated from the
      second Sepharose CL-4B peak, and had average glycosaminoglycan hydrodynamic sizes
      of approx. 25 kDa and 32 kDa respectively. Glycosaminoglycan chains of the
      aggrecan, biglycan and decorin were treated with chondroitin ABC lyase,
      chondroitin AC lyase and chondroitin B lyase to determine the positions of
      sulphation and the degree of uronic acid epimerization. The aggrecan
      glycosaminoglycan chains were found to contain a 4-sulphate/6-sulphate ratio of
      7:3, with no epimerization of glucuronic acid to iduronic acid. The biglycan
      glycosaminoglycan chains were found to contain a similar ratio of 4-sulphate/6
      sulphate, but with approx. 40-45% of the glucuronic acid epimerized to iduronic
      acid. The decorin glycosaminoglycan chains were found to contain 4-sulphate but
      no detectable 6-sulphate, and approx. 30-35% epimerization of the glucuronic acid
      to iduronic acid. The results, using these cloned cells, indicated that a single
      MC615 cell is able to make all three proteoglycans with distinctive differences
      between the glycosaminoglycans of aggrecan, biglycan and decorin. These data
      indicate that a mechanism must exist for a single MC615 cell to regulate the
      sizes and fine structures of glycosaminoglycans on simultaneously produced,
      different proteoglycans in a core-protein-specific manner.

PMID- 9581565
TI  - RNA minihelices as model substrates for ATP/CTP:tRNA nucleotidyltransferase.
AB  - Twenty-one RNA minihelices, resembling the coaxially stacked acceptor- /T-stems
      and T-loop found along the top of a tRNA's three-dimensional structure, were
      synthesized and used as substrates for ATP/CTP:tRNA nucleotidyltransferases from
      Escherichia coli and Saccharomyces cerevisiae. The sequence of nucleotides in the
      loop varied at positions corresponding to residues 56, 57 and 58 in the T-loop of
      a tRNA. All minihelices were substrates for both enzymes, and the identity of
      bases in the loop affected the interaction. In general, RNAs with purines in the
      loop were better substrates than those with pyrimidines, although no single base
      identity absolutely determined the effectiveness of the RNA as substrate. RNAs
      lacking bases near the 5'-end were good substrates for the E. coli enzyme, but
      were poor substrates for that from yeast. The apparent Km values for selected
      minihelices were 2-3 times that for natural tRNA, and values for apparent Vmax
      were lowered 5-10-fold.

PMID- 9581564
TI  - The N-terminal Arg2, Arg3 and Arg4 of human lactoferrin interact with sulphated
      molecules but not with the receptor present on Jurkat human lymphoblastic T
      cells.
AB  - We previously characterized a 105 kDa receptor for human lactoferrin (hLf) on
      Jurkat human lymphoblastic T-cells. To delineate the role of the basic cluster
      Arg2-Arg3-Arg4-Arg5 of hLf in the interaction with Jurkat cells, we isolated N
      terminally deleted hLf species of molecular mass 80 kDa lacking two, three or
      four N-terminal residues (hLf-2N, hLf-3N and hLf-4N) from native hLf that had
      been treated with trypsin. Native hLf bound to 102000 sites on Jurkat cells with
      a dissociation constant (Kd) of 70 nM. Consecutive removal of N-terminal arginine
      residues from hLf progressively increased the binding affinity but decreased the
      number of binding sites on the cells. A recombinant hLF mutant lacking the first
      five N-terminal residues (rhLf-5N) bound to 17000 sites with a Kd of 12 nM. The
      binding parameters of bovine lactoferrin (Lf) and native hLf did not
      significantly differ, whereas the binding parameters of murine Lf (8000 sites; Kd
      30 nM) resembled those of rhLf-5N. Culture of Jurkat cells in the presence of
      chlorate, which inhibits sulphation, decreased the number of binding sites for
      both native hLf and hLf-3N but not for rhLf-5N, indicating that the hLf-binding
      sites include sulphated molecules. We propose that the interaction of hLf with a
      large number of binding sites (approx. 80000 per cell) on Jurkat cells is
      dependent on Arg2-Arg3-Arg4, but not on Arg5. Interaction with approx. 20000
      binding sites per cell, presumably the hLf receptor, does not require the first N
      terminal basic cluster of hLf. Moreover, the affinity of hLf for the latter
      binding site is enhanced approx. 6-fold after removal of the first basic cluster.
      Thus N-terminal proteolysis of hLf in vivo might serve to modulate the nature of
      its binding to cells and thereby its effects on cellular physiology.

PMID- 9581566
TI  - A re-examination in vivo of the phosphatidylcholine-galactolipid metabolic
      relationship during plant lipid biosynthesis.
AB  - It remains unclear how and in what form the lipids synthesized in plant
      endoplasmic reticulum are exported to chloroplasts and used as precursors for the
      biosynthesis of plastid galactolipids, which are the most abundant lipids on
      Earth. Neither the mechanism of transfer nor the nature of the lipids imported
      into plastids has been elucidated. To characterize events occurring in vivo, the
      labelling of lipids from 15-day-old leek seedlings (Allium porrum, var. furor)
      was studied using pulse-chase experiments. During the chase, a substantial
      decline in the radioactivity incorporated into phosphatidylcholine (and not in
      other phospholipids) was accompanied by an increase in the label found in
      galactolipids. The positional distribution of labelled fatty acids in
      phosphatidylcholine and galactolipids was further studied as a function of the
      chase time; whereas phosphatidylcholine was preferentially labelled at the sn-2
      position, the increase in radioactivity in galactolipids mainly concerned the sn
      1 position. These results strongly suggest that the diacylglycerol moiety of
      phosphatidylcholine might not be integrated as a whole in the galactolipid.

PMID- 9581567
TI  - Superagonistic behaviour of epidermal growth factor/transforming growth factor
      alpha chimaeras: correlation with receptor routing after ligand-induced
      internalization.
AB  - Human epidermal growth factor (EGF) and human transforming growth factor alpha
      (TGF-alpha) are structurally related polypeptide growth factors that exert their
      mitogenic activity through interaction with a common cell-surface receptor, the
      epidermal growth factor receptor (EGFR). The biological effect induced by these
      two ligands is quantitatively similar in most cases; in some test systems,
      however, TGF-alpha functions as a more potent form of EGF. In this study, we have
      compared EGF, TGF-alpha and ten previously described chimaeras of these two
      ligands in terms of their ability to generate a mitogenic response in cells
      carrying the human EGFR, and observed that three of the mutant growth factors
      (E3T, E4T and T3E4T) are mitogenic at concentrations 10-fold lower than that of
      either wild-type EGF or TGF-alpha. No difference in tyrosine kinase activity of
      the receptor towards an external substrate was observed after binding of the
      various mutants. It has been established before [Ebner and Derynck (1991) Cell
      Regulation 2, 599-612] that EGF and TGF-alpha differ in the processing of the
      receptor-ligand complex after internalization, as a result of their different pH
      sensitivities of receptor binding. Similar measurements on our chimaeric mutants
      revealed that the above superagonists show an enhanced pH dependence of binding
      in comparison with EGF. Furthermore, induction of receptor recycling by these
      superagonists is largely comparable with that induced by TGF-alpha. No
      superagonistic behaviour was observed on a cell-line containing an EGFR/erbB-2
      chimaera which does not show ligand-induced internalization. These data show that
      EGF/TGFalpha chimaeras can be more active than the naturally occurring ligands,
      and that receptor recycling after ligand-induced internalization seems to be a
      prerequisite for this phenomenon.

PMID- 9581569
TI  - Role of Arg-401 of cytosolic serine hydroxymethyltransferase in subunit assembly
      and interaction with the substrate carboxy group.
AB  - In an attempt to identify the arginine residue involved in binding of the
      carboxylate group of serine to mammalian serine hydroxymethyltransferase, a
      highly conserved Arg-401 was mutated to Ala by site-directed mutagenesis. The
      mutant enzyme had a characteristic visible absorbance at 425 nm indicative of the
      presence of bound pyridoxal 5'-phosphate as an internal aldimine with a lysine
      residue. However, it had only 0.003% of the catalytic activity of the wild-type
      enzyme. It was also unable to perform reactions with glycine, beta-phenylserine
      or d-alanine, suggesting that the binding of these substrates to the mutant
      enzyme was affected. This was also evident from the interaction of amino
      oxyacetic acid, which was very slow (8.4x10(-4) s-1 at 50 microM) for the R401A
      mutant enzyme compared with the wild-type enzyme (44.6 s-1 at 50 microM). In
      contrast, methoxyamine (which lacks the carboxy group) reacted with the mutant
      enzyme (1.72 s-1 at 250 microM) more rapidly than the wild-type enzyme (0.2 s-1
      at 250 microM). Further, both wild-type and the mutant enzymes were capable of
      forming unique quinonoid intermediates absorbing at 440 and 464 nm on interaction
      with thiosemicarbazide, which also does not have a carboxy group. These results
      implicate Arg-401 in the binding of the substrate carboxy group. In addition, gel
      filtration profiles of the apoenzyme and the reconstituted holoenzyme of R401A
      and the wild-type enzyme showed that the mutant enzyme remained in a tetrameric
      form even when the cofactor had been removed. However, the wild-type enzyme
      underwent partial dissociation to a dimer, suggesting that the oligomeric
      structure was rendered more stable by the mutation of Arg-401. The increased
      stability of the mutant enzyme was also reflected in the higher apparent melting
      temperature (Tm) (61 degrees C) than that of the wild-type enzyme (56 degrees C).
      The addition of serine or serinamide did not change the apparent Tm of R401A
      mutant enzyme. These results suggest that the mutant enzyme might be in a
      permanently 'open' form and the increased apparent Tm could be due to enhanced
      subunit interactions.

PMID- 9581570
TI  - A tyrosine residue essential for catalytic activity in aminopeptidase A.
AB  - Aminopeptidase A (EC 3.4.11.7; APA) is a 130 kDa membrane-bound zinc enzyme that
      contains the consensus sequence HEXXH (residues 385-389) conserved among the zinc
      metalloprotease family. In this motif, both histidine residues and the glutamic
      residue were shown to be involved respectively in zinc co-ordination and
      catalytic activity. Treatment of APA with N-acetylimidazole results in a loss of
      enzymic activity; this is prevented by the competitive aminopeptidase inhibitor
      amastatin, suggesting the presence of an important tyrosine, lysine or cysteine
      residue at the active site of APA. A tyrosine residue was previously proposed to
      be involved in the enzymic activity of aminopeptidase N. Furthermore sequence
      alignment of mouse APA with other monozinc aminopeptidases indicates the presence
      of a conserved tyrosine (Tyr-471 in APA). The functional role of Tyr-471 in APA
      was investigated by replacing this residue with a phenylalanine (Phe-471) or a
      histidine (His-471) residue by site-directed mutagenesis. Kinetic studies showed
      that the Km values of both mutants were similar to that of the wild-type enzyme,
      whereas kcat values were decreased by three orders of magnitude and corresponded
      to a variation in free energy of the rate-limiting step by 4.0 and 4.2 kcal/mol
      (0.96 and 1.00 kJ/mol) for the Phe-471 and His-471 mutants respectively. The
      mutation did not modify the inhibitory potency of a thiol-containing inhibitor
      that strongly chelates the active-site zinc ion, whereas that of a putative
      analogue of the transition state presumed to mimic the reaction intermediate was
      reduced. Taken together, these results strongly suggest that the Tyr-471 hydroxy
      group participates in catalysis by stabilizing the transition state complex
      through interaction with the oxyanion.

PMID- 9581568
TI  - CD45 and RPTPalpha display different protein tyrosine phosphatase activities in T
      lymphocytes.
AB  - To examine the substrate specificity and function of two receptor protein
      tyrosine phosphatases, CD45 and RPTPalpha, RPTPalpha was expressed in a CD45(-),
      T-cell receptor (TCR)+, BW5147 T-lymphoma cell. High levels of expression of
      RPTPalpha did not fully restore either proximal or distal TCR-mediated signalling
      events. RPTPalpha was unable to reconstitute the phosphorylation of CD3zeta and
      did not increase the expression of the activation marker, CD69, on stimulation
      with TCR/CD3. RPTPalpha did not significantly alter the phosphorylation state or
      kinase activity of two CD45 substrates, p56(lck) or p59(fyn), suggesting that
      RPTPalpha does not have the same specificity or function as CD45 in T-cells.
      Further comparison of the two phosphatases indicated that immunoprecipitated
      RPTPalpha was approx. one-seventh to one-tenth as active as CD45 when tested
      against artificial substrates. This difference in activity was also observed in
      vitro with purified recombinant enzymes at physiological pH. Additional analysis
      with Src family phosphopeptides and recombinant p56(lck) as substrates indicated
      that CD45 was consistently more active than RPTPalpha, having both higher Vmax
      and lower Km values. Thus CD45 is intrinsically a much more active phosphatase
      than RPTPalpha, which provides one reason why RPTPalpha cannot effectively
      dephosphorylate p56(lck) and substitute for CD45 in T-cells. This work
      establishes that these two related protein tyrosine phosphatases are not
      interchangeable in T-cells and that this is due, at least in part, to
      quantitative differences in phosphatase activity.

PMID- 9581571
TI  - Purification of Escherichia coli acetohydroxyacid synthase isoenzyme II and
      reconstitution of active enzyme from its individual pure subunits.
AB  - The first step in the biosynthesis of branched-chain amino acids is catalysed by
      acetohydroxyacid synthase (EC 4.1.3.18). The reaction involves the
      decarboxylation of pyruvate followed by condensation with either a second
      molecule of pyruvate or with 2-oxobutyrate. The enzyme requires as cofactors
      thiamine diphosphate, a divalent metal ion and, usually, FAD. In most bacteria
      the enzyme is a heterotetramer of two large and two small subunits. Escherichia
      coli contains three active isoenzymes and the present study concerns isoenzyme
      II, whose large and small subunits are encoded by the ilvG and ilvM genes
      respectively. Cloning these genes into a plasmid vector and overexpression in E.
      coli allowed a two-step purification procedure for the native enzyme to be
      developed. The level of expression is considerably higher from a vector that
      introduces a 50 residue N-terminal fusion containing an oligohistidine sequence
      on the large subunit. Purification to homogeneity was achieved in a single step
      by immobilized-metal-affinity chromatography. The kinetic properties of the
      native and fusion enzyme are indistinguishable with respect to the substrate
      pyruvate and the inhibitor chlorsulfuron. The individual subunits were expressed
      as oligohistidine-tagged fusion proteins and each was purified in a single step.
      Neither subunit alone has significant enzymic activity but, on mixing, the enzyme
      is reconstituted. The kinetic properties of the reconstituted enzyme are very
      similar to those of the fusion enzyme. It is proposed that the reconstitution
      pathway involves successive, and highly co-operative, binding of two small
      subunit monomers to a large subunit dimer. None of the cofactors is needed for
      subunit association although they are necessary for the restoration of enzymic
      activity.

PMID- 9581572
TI  - T-tubule membranes from chicken skeletal muscle possess an enzymic cascade for
      degradation of extracellular ATP.
AB  - The chicken T-tubule Mg2+-ATPase is an integral membrane glycoprotein that
      presents properties different from those of other ATPases located in skeletal
      muscle cells and exhibits ATP-hydrolysing activity on the extracellular side of
      the transverse tubule (TT) membranes. In this study we demonstrate that TT
      vesicles purified from chicken skeletal muscle possess ecto-ADPase and ecto-5'
      nucleotidase activities that, along with ecto-ATPase, are able to sequentially
      degrade extracellular ATP to ADP, AMP and adenosine. Characterization studies of
      these TT ectonucleotidases revealed remarkable differences between ecto-ATPase
      and ecto-ADPase activities with respect to thermal stability, temperature
      dependence of the hydrolytic activity, effect of ionic strength, kinetic
      behaviour, divalent cation preference and responses to azide, N-ethylmaleimide,
      NaSCN, Triton X-100 and concanavalin A. Ecto-ATPase, but not ecto-ADPase, was
      inhibited by a polyclonal antibody against the chicken TT ecto-ATPase. On the
      basis of these results we propose that ATP and ADP hydrolysis are accomplished by
      two distinct enzymes and therefore the TT ecto-ATPase is not an apyrase. 5'
      Nucleotidase activity was inhibited by adenosine 5'-[alpha,beta
      methylene]diphosphate and concanavalin A, followed simple Michaelis-Menten
      kinetics and was released from the membranes by treatment with
      phosphatidylinositol-specific phospholipase C, indicating that AMP hydrolysis in
      T-tubules is catalysed by a typical ecto-5'-nucleotidase. Results obtained from
      electrophoresis experiments under native conditions suggest that ecto-ATPase,
      ecto-ADPase and 5'-nucleotidase might be associated, forming functional complexes
      in the T-tubule membranes. The TT ectonucleotidases constitute an enzymic cascade
      for the degradation of extracellular ATP that might be involved in the regulation
      of purinergic signalling in the muscle fibre.

PMID- 9581573
TI  - Characterization of maize (Zea mays) pollen profilin function in vitro and in
      live cells.
AB  - Profilin is a small, 12-15 kDa, actin-binding protein that interacts with at
      least three different ligands. The 1:1 interaction of profilin with globular
      actin (G-actin) was originally thought to provide a mechanism for sequestering
      actin monomers in the cytoplasm. It has recently become clear that the role of
      profilin in the cell is more complex, perhaps due to interactions with
      polyphosphoinositides and proline-rich proteins, or due to the ability to lower
      the critical concentration for actin assembly at the fast-growing barbed end of
      actin filaments. Because actin-binding proteins have been shown to behave
      differently with heterologous sources of actin, we characterized the interaction
      between maize pollen profilins and plant G-actin. The equilibrium dissociation
      constants measured by tryptophan fluorescence quenching were similar to those of
      other CaATP-G-actin-profilin complexes (Kd=1.0-1.5 microM). The ability of maize
      profilin isoforms to bind poly-l-proline was analysed, and the Kd values for
      recombinant pollen and human profilins were similar when determined by two
      independent methods. However, the affinity of native maize pollen profilin for
      poly-l-proline was substantially lower than that of any of the recombinant
      proteins by one of these assays. The possibility of post-translational
      modification of profilin in the mature pollen grain is discussed. Finally, we
      quantified the effects of microinjection of each profilin isoform on the
      cytoarchitecture of Tradescantia stamen hair cells and show that the resultant
      disruption can be used to compare actin-binding proteins in living cells. The
      results are discussed in relation to a recent model of the interphase actin array
      in these plant cells.

PMID- 9581576
TI  - The enzyme glucosidase II is induced in response to amino acid deprivation in
      renal epithelial cells.

PMID- 9581574
TI  - Major co-localization of the extracellular-matrix degradative enzymes heparanase
      and gelatinase in tertiary granules of human neutrophils.
AB  - The expression of cell-surface adhesion proteins and the release of extracellular
      matrix degradative enzymes constitute crucial processes for the attachment of
      neutrophils to the endothelium and for the subsequent extravasation of these
      cells through the endothelial layer. We have analysed in resting human
      neutrophils the subcellular localization of heparanase, a heparan-sulphate
      degrading endoglycosidase that can degrade basement-membrane components, thereby
      facilitating neutrophil passage into the tissue during an inflammatory reaction.
      By subcellular fractionation of postnuclear supernatants from resting human
      neutrophils on continuous sucrose gradients, we have found that heparanase
      activity was mainly located in gelatinase-containing tertiary granules. Using a
      specific antibody, the 96-kDa heparanase protein was further located in the
      gelatinase-rich subcellular fractions. Following immunoblotting and
      immunoprecipitation analysis in the distinct subcellular fractions, we also found
      co-localization of heparanase and Mo1 (CD11b/CD18), a leucocyte integrin involved
      in the attachment of neutrophils to the endothelium, in the fractions enriched in
      gelatinase-containing tertiary granules. Treatment of human neutrophils with
      tumour necrosis factor or granulocyte/macrophage colony-stimulating factor
      induced an increase in the CD11b/CD18 cell-surface expression, as well as the
      release of both gelatinase (matrix metalloproteinase-9) and heparanase, but not
      of other granule markers, indicating a major co-localization of gelatinase,
      heparanase and CD11b/CD18 in the same organelle. Furthermore, confocal laser
      scanning microscopy using specific antibodies against gelatinase and heparanase
      revealed a major co-localization of both enzymes in intracellular cytoplasmic
      granules. The major localization of heparanase and CD11b/CD18 in the gelatinase
      containing tertiary granule supports the notion that mobilization of this
      organelle can regulate extravasation of human neutrophils.

PMID- 9581577
TI  - Dr. William J. Mayo's association with noted southern surgeons.

PMID- 9581578
TI  - Influence of prostate-specific antigen testing on the spectrum of patients with
      prostate cancer undergoing radical prostatectomy at a large referral practice.
AB  - OBJECTIVE: To analyze trends in the clinical stage and pathologic outcome of
      patients with prostate cancer who underwent radical prostatectomy at a large
      referral practice during the prostate-specific antigen (PSA) testing era.
      MATERIAL AND METHODS: Between January 1987 and June 1995, 5,568 patients with
      prostate cancer (4,774 with clinically localized disease of stage T2c or less)
      underwent pelvic lymphadenectomy and radical retropubic prostatectomy at our
      institution. Patient age, preoperative serum PSA level, clinical stage,
      pathologic stage, Gleason score, and tumor ploidy were assessed. Outcome was
      based on clinical and PSA (increases in PSA level of 0.2 ng/mL or more)
      progression-free survival. RESULTS: Patient age (65 to 63 years old; P<0.001) and
      serum PSA level (median, 8.4 to 6.8 ng/mL; P<0.001) decreased during the study
      period. The percentage of patients with clinical stage T1c prostate cancer
      increased from 2.1% in 1987 to 36.4% in 1995 (P<0.001), and clinical stage T3
      cancer decreased from 25.3% to 6.5% (P<0.001). Nondiploid tumors decreased from
      38.3% to 24.6% (P<0.001), and the proportion of patients with pathologically
      organ-confined disease increased from 54.9% to 74.3% (P<0.001). More cT1c than
      cT2 tumors were diploid (80% versus 72%; P<0.001), had a Gleason score of 7 or
      less (75% versus 65%; P<0.001), and were confined to the prostate (75% versus
      57%; P<0.001). Five-year progression-free survival was 85% and 76% for patients
      with clinical stage T1c and T2, respectively (P<0.001). CONCLUSION: Since the
      advent of PSA testing, patients referred to our institution for radical
      prostatectomy have shown a significant migration to lower-stage, less-nondiploid,
      more often organ-confined prostate cancer at the time of initial assessment.
      Cancer-free survival associated with PSA-detected cancer (cT1c) is superior to
      that with palpable tumors (cT2). Whether these trends translate into improved
      long-term cancer-specific survival remains to be confirmed with longer follow-up.

PMID- 9581575
TI  - Mutagenesis of Glu403 to Cys in rabbit neutral endopeptidase-24.11 (neprilysin)
      creates a disulphide-linked homodimer: analogy with endothelin-converting enzyme.
AB  - Neutral endopeptidase-24.11 (NEP; neprilysin; EC 3.4.24.11) and endothelin
      converting enzyme (ECE) are related zinc metallopeptidases involved in the
      processing of biologically active peptides. Only ECE, however, exists as a
      disulphide-linked homodimer. The covalent linkage in rat ECE is between Cys412 in
      each subunit, which is equivalent to Glu403 in rabbit NEP. Here we report that
      directed mutagenesis of Glu403 to cysteine in rabbit NEP creates a disulphide
      linked homodimer, as revealed by transient transfection in COS-1 cells and
      SDS/PAGE of a membrane fraction. Under reducing conditions, both the mutant
      (E403C) and the wild-type NEP migrate as a polypeptide of 92 kDa. However, under
      non-reducing conditions, the Mr of the wild type remains unchanged, whereas that
      of the mutant is doubled. Co-transfection of wild-type ECE and E403C NEP cDNA did
      not result in the production of a NEP-ECE heterodimer. Comparison of the kinetic
      constants for wild-type and E403C mutant NEP with either [D-Ala2,Leu5]enkephalin
      or 3-carb oxypropanoyl-alanyl-alanyl- leucine-4-nitroanilide(Suc-Ala-Ala-Leu-NH
      Np) as substrate show a decrease of approx. 50% in Vmax/Km for the mutant form.
      The IC50 value for inhibition of the mutant by phosphoramidon or thiorphan is
      increased 3-fold and 5-fold respectively. Although NEP and ECE exhibit only about
      40% identity and differ substantially in substrate specificity and some other
      characteristics, these data indicate that they have considerable similarity in
      three-dimensional structure, allowing dimer formation in the mutant NEP with the
      disulphide link probably occurring in a hydrophilic surface loop.

PMID- 9581579
TI  - Topical psoralen-ultraviolet A therapy for palmoplantar dermatoses: experience
      with 35 consecutive patients.
AB  - OBJECTIVE: To report the effectiveness of topical psoralen-ultraviolet A (PUVA)
      therapy for palmoplantar dermatoses and to describe our method of administration
      of this treatment modality. DESIGN: We conducted a retrospective study of 35
      patients, 27 to 66 years of age, who received topical hand and foot PUVA therapy.
      MATERIAL AND METHODS: Ten patients had psoriasis vulgaris, 8 had pustular
      psoriasis, 5 had dyshidrotic eczema, and 12 had other types of dermatitis. The
      affected area was soaked in a psoralen solution, 0.0005% methoxsalen (10 mg of
      methoxsalen in 2 L of warm water), for 30 minutes and then exposed to incremental
      amounts of ultraviolet A light three times weekly until the dermatosis subsided
      or cleared. Treatment frequency was then reduced and ultimately discontinued.
      Time to maximal improvement of the hands and feet was defined as the period from
      the beginning of PUVA treatment to the point at which the frequency of treatment
      was reduced from three times weekly to twice weekly. RESULTS: Fourteen patients
      (40%) had clearing of their disease, and 14 others (40%) had improvement of their
      conditions. The mean time to clearing was 2.8 months (range, 2 weeks to 7
      months), and the mean number of treatments was 27.3 (range, 10 to 55). The mean
      total dose of ultraviolet A received was 140 J/cm2 (range, 9 to 530). Two
      patients (6%) had no response to treatment. Mild localized ultraviolet-related
      erythema developed in 16 patients (46%). Five patients "dropped out" of
      treatment, and nine other patients discontinued treatment during maintenance
      therapy. The principal reason cited was inconvenience. CONCLUSION: Topical PUVA
      therapy is an effective and safe treatment option for recalcitrant dermatoses
      affecting the palms and soles.

PMID- 9581580
TI  - GB virus-C infection in type 1 autoimmune hepatitis.
AB  - OBJECTIVE: To assess the frequency and significance of GB virus-C infection in
      type 1 autoimmune hepatitis. MATERIAL AND METHODS: Serum specimens from 94
      patients with type 1 autoimmune hepatitis were tested for GB virus-C RNA by
      reverse transcription and polymerase chain reaction. Serum samples from 50 normal
      subjects were also assessed. RESULTS: Three of the 94 specimens from patients
      with autoimmune hepatitis were positive for GB virus-C RNA in comparison with
      none of the 50 control samples (3% versus 0%; P = 0.5). Two patients were
      seropositive after variceal hemorrhage and blood transfusion, including one
      patient who clearly acquired the infection in this fashion. One patient had no
      epidemiologic basis for his seropositivity. Viremia was prolonged in all infected
      patients (mean duration, 69 +/- 23 months; range, 36 to 113); however, no
      clinical features suggested a concurrent viral infection, and mortality was
      similar to that among the uninfected counterparts (33% versus 8%; P = 0.2). Liver
      transplantation was more common in the infected patients (67% versus 9%; P =
      0.03), but the duration of disease was also longer in these patients (277 +/- 29
      months versus 106 +/- 9 months; P = 0.0008). Clinical features and immediate
      responses to corticosteroid therapy were similar in both groups. CONCLUSION: GB
      virus-C RNA is found infrequently in type 1 autoimmune hepatitis, and GB virus-C
      is unlikely to be an important etiologic agent or prognostic determinant.

PMID- 9581581
TI  - The preparticipation physical examination: Mayo Clinic experience with 2,739
      examinations.
AB  - OBJECTIVE: To report the results of preparticipation physical examination (PPE)
      performed on 2,739 high school athletes and present a model for providing PPEs in
      similar practice settings. DESIGN: We analyzed 2,739 PPEs performed on high
      school athletes by means of a station examination approach in our Sports Medicine
      Center during a 3-year period. MATERIAL AND METHODS: Personnel from the
      Departments of Physical Medicine and Rehabilitation, Orthopedics, Family
      Medicine, and Internal Medicine participated in performance of a comprehensive
      station-based physical examination of high school athletes. The final reviewing
      physician assigned one of three dispositions to each athlete: cleared for
      participation in sports, not cleared, or cleared with follow-up recommended.
      RESULTS: On the basis of PPE findings, 53 athletes (1.9%) were disqualified from
      participation in sports. Abnormalities that did not preclude participation but
      necessitated follow-up were identified in another 327 athletes (11.9%).
      Musculoskeletal problems were the leading cause of restriction from sports
      activities (43.4%) and the second leading cause for recommended follow-up
      (27.8%). Clinically significant cardiac abnormalities were noted in only 10
      athletes (0.37% of the overall group of students). Our methods and results are
      discussed in relationship to previous PPE studies. CONCLUSION: On the basis of
      this study, we conclude that (1) a Sports Medicine Clinic can efficiently
      administer PPEs to a large number of athletes by using an adaptable station
      approach, (2) the musculoskeletal component of a PPE is an important part of the
      process that often reveals abnormalities and should be performed by qualified
      personnel, and (3) each practice must refine its delivery of PPEs on the basis of
      its particular environment.

PMID- 9581583
TI  - Contemporary urologic management of patients with spinal cord injury.
AB  - Urologic management strategies in patients with spinal cord injury are discussed
      herein, and the underlying pathophysiology and urodynamic principles are
      emphasized. Contemporary management of the spinal cord-injured bladder has
      allowed for near-elimination of renal failure as the primary cause of long-term
      morbidity in these patients; low urine storage, sterile urine, and effective
      emptying are imperative for good long-term results.

PMID- 9581582
TI  - Suppression of frequent premature ventricular contractions and improvement of
      left ventricular function in patients with presumed idiopathic dilated
      cardiomyopathy.
AB  - OBJECTIVE: To examine the hypothesis that suppression of frequent premature
      ventricular contractions may be associated with improvement in left ventricular
      function in patients with presumed idiopathic dilated cardiomyopathy. DESIGN: We
      conducted a retrospective case study and statistical analysis of the effect of
      cardiac medical therapy on outcome. MATERIAL AND METHODS: The study population
      consisted of 14 patients with more than 20,000 premature ventricular contractions
      in 24 hours recorded by Holter monitoring and associated left ventricular
      dysfunction (ejection fraction, 40% or less). Clinical characteristics, number of
      premature ventricular contractions per hour on 24-hour ambulatory Holter
      monitoring, and ejection fraction based on transthoracic echocardiography were
      compared before and after cardiac therapeutic intervention. RESULTS: Of the 14
      patients, 10 had presumed idiopathic dilated cardiomyopathy, and 4 had ischemic
      heart disease. Of the overall study group, seven had received additional cardiac
      medical therapy after the index evaluation, including four patients who had
      amiodarone therapy. A significant reduction (75% or more from baseline) in
      premature ventricular contractions after medical therapeutic intervention was
      observed in five patients at the first follow-up examination. The mean interval
      to the first follow-up examination was 6 +/- 3 months. Of the five patients, four
      had significant improvement in clinical functional status and the ejection
      fraction. The mean ejection fraction of these five patients increased from 27 +/-
      10% at baseline to 49 +/- 17% after medical therapy (P = 0.04). CONCLUSION: The
      suppression of frequent premature ventricular contractions may be associated with
      improvement of left ventricular function in patients with presumed idiopathic
      dilated cardiomyopathy.

PMID- 9581584
TI  - Regression of acquired immunodeficiency syndrome-related pulmonary Kaposi's
      sarcoma after highly active antiretroviral therapy.
AB  - Kaposi's sarcoma (KS) is the most common neoplasm affecting people with the human
      immunodeficiency virus (HIV) infection. The skin is the most common site of
      disease; however, KS can also involve visceral organs such as the lungs, leading
      to severe morbidity and contributing to death in almost 30% of patients with the
      acquired immunodeficiency syndrome (AIDS). New antiretroviral strategies
      incorporating combination nucleoside analogues with a protease inhibitor lead to
      increased circulating CD4+ lymphocyte counts, decreased plasma levels of HIV, and
      decreased mortality from AIDS-defining opportunistic infections. The effects of
      highly active antiretroviral therapy (HAART) on AIDS-associated KS remain largely
      unknown. Herein the case of an antiretroviral-naive man with advanced AIDS (CD4+
      helper T-lymphocyte count, 35/mm3; HIV viral RNA quantification, more than
      800,000 copies/mL), and symptomatic pulmonary KS is described. After HAART was
      initiated, his CD4+ cell count increased fourfold, his HIV-viral load decreased
      to nondetectable levels, and the pulmonary KS regressed dramatically. To my
      knowledge, this report represents the first documented case of pulmonary KS
      regression after the initiation of HAART. Although this finding is preliminary,
      if confirmed by other clinicians, the effect of potent antiretrovirals on KS
      growth and development will have important implications on the manner in which KS
      is staged and treated.

PMID- 9581585
TI  - Giant cell (temporal) arteritis: involvement of the vertebral and internal
      carotid arteries.
AB  - We report the radiographic findings in a case of histologically proven giant cell
      (temporal) arteritis coupled with high-grade stenoses affecting the internal
      carotid and vertebral arteries. The 69-year-old patient sought medical assessment
      because of transient ischemic attacks. The stenoses, which were extradural just
      proximal to the dural entry point, were thought to be a manifestation of the
      giant cell arteritis.

PMID- 9581586
TI  - Localized lymphoplasmacellular pancreatitis forming a pancreatic inflammatory
      pseudotumor.
AB  - Inflammatory pseudotumors (IPTs) of the pancreas are rare. To our knowledge, we
      report the first case of a pancreatic IPT composed of dense lymphocytic and
      plasmacellular infiltrates that histologically resembled a primary
      lymphoplasmacytic lymphoma of the pancreas. In addition, it is the first
      pancreatic IPT analyzed for latent Epstein-Barr virus, an agent implicated in the
      pathogenesis of IPTs of the liver and spleen.

PMID- 9581587
TI  - D-lactic acidosis: pathologic consequence of saprophytism.
AB  - In this report, we describe a 50-year-old woman with a short bowel who had
      recurrent episodes of weakness, ataxia, slurred speech, confusion, and nausea. D
      Lactic acidosis was diagnosed on the basis of a D-lactate level of 8.2 mmol/L
      (normal, 0 to 0.25) obtained during an episode of confusion. D-Lactic acidosis is
      a potentially fatal clinical condition seen in patients with a short small
      intestine and an intact colon. Excessive production of D-lactate by abnormal
      bowel flora overwhelms normal metabolism of D-lactate and leads to an
      accumulation of this enantiomer in the blood. This disorder provides insight into
      the role of intestinal flora in human metabolism and demonstrates the manner in
      which altered intestinal flora can produce disease in humans. Increased awareness
      of D-lactic acidosis is necessary for prompt and appropriate treatment. The
      pathophysiology and treatment of D-lactic acidosis are reviewed.

PMID- 9581588
TI  - Management of Barrett's esophagus.
AB  - In Barrett's esophagus, the squamous lining of the lower esophagus is replaced by
      columnar epithelium. Barrett's esophagus is associated with gastroesophageal
      reflux and an increased risk of the development of esophageal cancer. Endoscopy
      shows red columnar epithelium in the lower esophagus. Biopsy is needed to confirm
      intestinal metaplasia. Some cases progress from dysplasia to invasive
      adenocarcinoma. Medical or surgical antireflux treatment controls symptoms and
      esophagitis, but Barrett's esophagus remains. Patients are usually followed up by
      endoscopy for detection of dysplasia or early cancer. For patients with low-grade
      dysplasia, follow-up is adequate; however, for those with high-grade dysplasia,
      esophagectomy or experimental endoscopic mucosal ablation is advised.

PMID- 9581589
TI  - Sune Bergstrom--Nobel Prize for prostaglandin studies.

PMID- 9581590
TI  - 29-year-old man with recurrent deep venous thrombosis and skin lesions.

PMID- 9581591
TI  - Sarcoidosis of the liver and bile ducts.
AB  - In sarcoidosis, granulomas are frequently present in multiple organs, including
      the liver. Typically, epithelioid granulomas (noncaseating) are scattered
      throughout the liver, but confluent granulomas can be present in cases with
      severe hepatic involvement. The characteristic inclusions in giant cells (for
      example, Schaumann bodies and asteroid bodies) are not seen in all cases and are
      not pathognomonic. The granulomas of sarcoidosis may heal without a trace, but
      confluent granulomas can result in extensive, irregular scarring. Occlusion of
      intrahepatic portal vein branches by the granulomatous inflammation probably
      accounts for the development of portal hypertension in some cases. A
      granulomatous cholangitis leading to ductopenia seems to be the underlying
      pathogenetic mechanism of the chronic cholestatic syndrome of sarcoidosis.
      Recognition of this syndrome is important in the differential diagnosis of other
      chronic cholestatic diseases, such as primary biliary cirrhosis or primary
      sclerosing cholangitis. Other rare complications of sarcoidosis are the Budd
      Chiari syndrome and obstructive jaundice attributable to hepatic hilar
      lymphadenopathy or strictures of the bile ducts.

PMID- 9581592
TI  - Bacterial and parasitic cholangitis.
AB  - Bacterial cholangitis is a clinically defined syndrome caused by the
      regurgitation of infected bile into the circulation. The pathogenic mechanism is
      unclear, and systemic sepsis may not occur. Prerequisite conditions are the
      presence of microorganisms in the bile and increased biliary pressure. Bacteria
      that commonly cause cholangitis are Escherichia coli, Klebsiella, Enterococcus,
      Enterobacter, Pseudomonas, and anaerobes. Although most infections are
      polymicrobial, this situation may not always prevail. Successful treatment
      depends on relieving biliary obstruction and administering antibiotics effective
      against bacteria in the circulation and the bile. The causes of biliary
      obstruction that predispose to bacterial cholangitis are myriad. Common
      conditions include biliary stones and benign strictures. In many parts of the
      world, biliary parasites are an important factor. Biliary parasites cause
      necrosis, inflammation, fibrosis, strictures, and cholangiectasis of the bile
      ducts by several mechanisms: (1) as a direct result of the irritating chemical
      composition of the parasite, parasitic secretions, or eggs; (2) physical
      obstruction of the bile ducts; (3) induction of formation of biliary stones; and
      (4) introduction of bacteria into the biliary system during migration from the
      duodenum. Therefore, bacterial cholangitis has an important and frequently
      dominant role in the pathogenesis and clinical course of biliary disease due to
      these parasitic infestations. Common biliary parasites include the nematode
      Ascaris lumbricoides, the trematodes Opisthorchis viverrini and felineus,
      Clonorchis sinensis, and Fasciola hepatica, and the cestodes Echinococcus
      granulosus and multilocularis. The epidemiologic, pathologic, and clinical
      manifestations of these parasitic infestations are reviewed.

PMID- 9581593
TI  - Cholangitis in viral disease.
AB  - This review of biliary manifestations of viral diseases includes aspects of
      morphologic diagnosis, therapeutic implications, prognostic effect, and natural
      history. The viral causes of cholangitis are reviewed, with subclassification on
      the basis of primary hepatic versus systemic infections and immune competence of
      the host. Special attention is given to the histopathologic and clinical features
      of viruses affecting the biliary tree. Among hepatotropic viruses, hepatitis C
      more frequently is associated with cholangitis than is hepatitis B. In both
      hepatitis B and hepatitis C, the lymphocytic cholangitis duct damage is
      reversible and does not adversely influence the course of disease or response to
      therapy. Hepatitis A and hepatitis E, despite causing clinical cholestasis, do
      not result in severe cholangitis. The effect of systemic viruses on the biliary
      tree is primarily dependent on the status of the host immune system. Infants and
      severely immunosuppressed patients (such as those who have undergone liver
      transplantation) are at risk for cytomegalovirus cholangitis, whereas patients
      with late-stage acquired immunodeficiency syndrome (AIDS) are at risk for
      cholangitis due to numerous organisms. Overall, cholangitis attributable to viral
      disease encompasses a wide spectrum of clinicopathologic scenarios, depending on
      the etiologic virus and the immune competence of the host.

PMID- 9581594
TI  - Psychiatry, managed care, and crooked thinking.

PMID- 9581595
TI  - Prostate cancer in the serum prostate-specific antigen era.

PMID- 9581596
TI  - Encapsulation and perfusion of mitochondria in agarose beads for functional
      studies with 31P-NMR spectroscopy.
AB  - An NMR method to study on-line mitochondrial function was developed. Mitochondria
      were maintained in a stable physiologic state in agarose beads that were
      continuously superfused with oxygenated buffer at 28 degrees C. Oxidative
      function of both heart and liver mitochondria was evaluated with 31P NMR at 9.4 T
      using pyruvate plus malate as substrate. This method allows clear resolution of
      adenosine triphosphate-gamma (ATPgamma) and adenosine diphosphate-beta (ADPbeta)
      phosphate signals, whereas alpha signals of ATP and ADP overlap. ATP production
      by mitochondria was documented to be very sensitive to different interventions
      (hypoxia, ischemia, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP))
      and depended on the ADP concentration in superfusion medium. These data
      demonstrate that the new application of NMR to study mitochondrial function can
      discriminate, on-line, between several physiologic and biochemical processes in
      intact physiologically stable mitochondria.

PMID- 9581597
TI  - Blood oxygen saturation assessment in vivo using T2* estimation.
AB  - The feasibility of noninvasively assessing hemoglobin oxygen saturation of deep
      blood vessels in vivo by measuring blood T2* is investigated. Techniques for
      blood T2* measurements in major arteries and veins in the presence of pulsatile
      blood flow are presented and validated using a flow phantom. Images of multiple
      TEs were collected in a paired fashion. Cardiac triggering was used to eliminate
      image artifacts caused by pulsatile arterial blood flow. Using these techniques,
      it was found that the T2* of arterial blood (199 +/- 8 ms) is significantly
      greater than that of venous blood (108 +/- 6 ms) in 10 volunteers, consistent
      with the fact that the oxygen saturation level of arterial blood is much larger
      than that of venous blood. Various oxygen saturation levels were created in vivo
      in a pig and the blood T2* was shown to increase with oxygen saturation levels
      over a wide range. Preliminary results of this study indicate that it is feasible
      to assess local oxygen saturation by measuring blood T2* using the proposed
      techniques.

PMID- 9581598
TI  - Timing algorithm for bolus chase MR digital subtraction angiography.
AB  - To acquire multiple longitudinal locations in the lower extremity after a single
      contrast injection, appropriate table translation and contrast injection are
      required. An approximate model based on constant bolus velocity was developed to
      describe the space-time course of a contrast bolus in the lower extremity. This
      model was verified in dynamic MR angiograms acquired in a group of patients using
      time-resolved 2D MR digital subtraction angiography (MRDSA). From this contrast
      bolus passage model, a timing algorithm for table translation and contrast
      injection was developed for bolus chase MRDSA, subsequently validated in bolus
      chase 2D MRDSA experiments. All targeted major peripheral arteries were well
      depicted in bolus chase 2D MRDSA using this timing algorithm and a single 15-ml
      contrast dose.

PMID- 9581599
TI  - Sodium MRI of human articular cartilage in vivo.
AB  - Preliminary results from in vivo sodium MRI of human patellar articular cartilage
      are presented. Sodium images generated of an in vitro bovine patella clearly
      distinguish the region of proteoglycan depletion from the region of healthy
      cartilage. This provides the first evidence that sodium imaging may be used to
      detect changes due to osteoarthritis in vivo. The process of optimizing imaging
      time and signal-to-noise ratio, as well as potential implications in the
      detection of osteoarthritic change, are discussed.

PMID- 9581600
TI  - Quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSS
      II).
AB  - In the pulsed arterial spin labeling (ASL) techniques EPISTAR, PICORE, and FAIR,
      subtraction of two images in which inflowing blood is first tagged and then not
      tagged yields a qualitative map of perfusion. An important reason this map is not
      quantitative is that there is a spatially varying delay in the transit of blood
      from the tagging region to the imaging slice that cannot be measured from a
      single subtraction. We introduce here two modifications of pulsed ASL (QUIPSS and
      QUIPSS II) that avoid this problem by applying additional saturation pulses to
      control the time duration of the tagged bolus, rendering the technique relatively
      insensitive to transit delays and improving the quantitation of perfusion.

PMID- 9581601
TI  - Simultaneous multislice acquisition using rosette trajectories (SMART): a new
      imaging method for functional MRI.
AB  - A new acquisition technique for rapid, whole-brain functional MRI is presented.
      In this technique, several slices are simultaneously acquired using rosette k
      space trajectories and a gradient-induced frequency modulation. This modulation
      together with the spectral properties of the rosette acquisition allow all slices
      to be reconstructed individually. In functional MRI studies, acquisition rates of
      16.7 to 25 images/s were achieved, a threefold improvement over single-slice
      acquisitions. The raw images showed some increase in noise. However, because this
      increase is mostly stationary, the functional activation maps showed only a
      slight increase in noise (8%).

PMID- 9581602
TI  - BASE imaging: a new spin labeling technique for measuring absolute perfusion
      changes.
AB  - A new technique for magnetic resonance imaging of absolute perfusion changes that
      uses magnetically labeled tissue water proton spins as a freely diffusible tracer
      is described. It consists of unprepared basis (BA) images that serve as a
      reference and selective (SE) inversion prepared images that are sensitive to
      perfusion changes. In the present study, the BASE technique was applied to
      functional neuroimaging. BA and SE images were alternatingly and repeatedly
      acquired during periods of visual stimulation and control. Visual stimulation was
      achieved with an alternating black/white checkerboard operating at a frequency of
      8 Hz. Maps of the absolute cerebral blood flow changes (deltaCBF) were calculated
      from the image intensities of the corresponding BA and SE images. The individual
      mean values of deltaCBF measured in five healthy volunteers ranged from 69 +/- 18
      to 99 +/- 26 ml/min/100 g. Since the BASE technique does not require nonselective
      spin inversion, it can be used with small transmit/receive head coils (e.g.,
      surface coils). In addition, the BASE technique is robust against a mismatch of
      the inversion and detection slice profiles.

PMID- 9581603
TI  - Heuristic optimization algorithms applied to the quantification of spectroscopic
      data.
AB  - The quantification of in vivo MR spectra imposes severe problems because of low
      spectral resolution and poor signal-to-noise ratio. Maximum likelihood methods
      are often applied. However, with conventional spectrum analysis procedures, the
      search for a global minimum in a multidimensional space often terminates in only
      a local minimum. Heuristic optimization procedures are able to circumvent this
      difficulty. Two approaches, the genetic algorithm and the simulated annealing,
      have been adapted to the quantification of MR spectra. For evaluation purposes,
      the procedures have been applied to synthetic and in vivo spectra with different
      noise levels. They both allowed a reliable spectrum quantification. The areas of
      most peaks were quantified reproducibly, although in some cases, the
      discrimination between spectroscopically almost identical metabolites (e.g.,
      glutamate and glutamine) was not completely satisfactory. The two algorithms are
      found to be valuable alternative methods in the quantification of in vivo MR
      spectra.

PMID- 9581604
TI  - Three-dimensional 31P magnetic resonance spectroscopic imaging of regional high
      energy phosphate metabolism in injured rat heart.
AB  - The purpose of this study was to measure the spatially varying 31P MR signals in
      global and regional ischemic injury in the isolated, perfused rat heart. Chronic
      myocardial infarcts were induced by occluding the left anterior descending
      coronary artery eight weeks before the MR examination. The effects of acute
      global low-flow ischemia were observed by reducing the perfusate flow. Chemical
      shift imaging (CSI) with three spatial dimensions was used to obtain 31P spectra
      in 54-microl voxels. Multislice 1H imaging with magnetization transfer contrast
      enhancement provided anatomical information. In normal hearts (n = 8), a
      homogeneous distribution of high-energy phosphate metabolites (HEP) was found. In
      chronic myocardial infarction (n = 6), scar tissue contained negligible amounts
      of HEP, but their distribution in residual myocardium was uniform. The size of
      the infarcted area could be measured from the metabolic images; the correlation
      of infarct sizes determined by histology and 31P MR CSI was excellent (P <
      0.006). In global low-flow ischemia (n = 8), changes of HEP showed substantial
      regional heterogeneity. Three-dimensional 31P MR CSI should yield new insights
      into the regionally distinct metabolic consequences of various forms of
      myocardial injury.

PMID- 9581605
TI  - Magnetization transfer attenuates metabolite signals in tumorous and
      contralateral animal brain: in vivo observations by proton NMR spectroscopy.
AB  - Tumorous and contralateral rat brain was examined by in vivo single voxel proton
      NMR spectroscopy. Magnetization transfer (MT) experiments cause attenuation of
      various metabolite signals. Selective saturation of immobile metabolites was
      achieved by pulsed RF preirradiation. The method is compared with continuous wave
      MT generation. In contralateral tissue, MT attenuation is detected for both the
      CH3 and the CH2 protons of (phospho-)creatine (Cr + PCr) and for a signal at 3.44
      ppm ascribed to taurine. Significant attenuation is also observed for a signal at
      3.78 ppm that is commonly ascribed to the alphaCH proton of glutamate and
      glutamine (Glx); however, no effect is observed for the gammaCH2 protons of Glx.
      Within implanted F98 glioma tumors, only the CH3 signal of Cr + PCr shows
      significant MT attenuation. Although the MT effect detected for lactate in the
      tumors fails to reach significance, a significant effect is observed for the
      lactate signal acquired during 3 to 9 min postmortem.

PMID- 9581606
TI  - In-plane motion correction for MR spectroscopic imaging.
AB  - A motion-detection method is described that is specifically suited for MR
      spectroscopic imaging (MRSI) studies. Information on in-plane rotation and
      translation of the subject was obtained using external spatial reference markers
      that are uniquely identified via their chemical shift. The marker locations were
      obtained directly from the acquired data at each encoding step, and no additional
      data acquisition was required. This method was applied to brain 1H MRSI studies
      that include subcutaneous lipid signals, which otherwise result in enhanced
      sensitivity to subject motion.

PMID- 9581607
TI  - Assessment of glucosylifosfamide mustard biodistribution in rats with prostate
      adenocarcinomas by means of in vivo 31P NMR and in vitro uptake experiments.
AB  - A combined in vitro/in vivo study was performed to evaluate the possible
      application of phosphorus (31P) NMR spectroscopy for therapy monitoring and to
      investigate glucosylifosfamide mustard (Glc-IPM) transport and biodistribution by
      radiotracer techniques. Dynamic in vivo 31P NMR measurements were performed in
      rats with prostate adenocarcinoma after i.v. injection of 1 mmol/kg body weight
      (bw) of ifosfamide (IFO) (n = 4) and 1 mmol/kg bw (n = 4) or 2.15 mmol/kg bw (n =
      9) of Glc-IPM. In a biodistribution study with 14C-labeled Glc-IPM and a final
      dose of 0.8 mmol Glc-IPM/kg bw, the animals were killed 5, 30, 60, and 120 min
      after drug administration, an ethanol extraction was performed from several
      tissues, and the dose per g tissue was calculated. The same tumor cell line was
      used in saturation and competition experiments to further elucidate the transport
      mechanism. The 31P NMR signals of IFO and Glc-IPM showed no overlap with the
      endogenous phosphorus peaks. A rapid washout with a half-life between 25.9 +/-
      5.6 min for the lower dose and 34.3 +/- 4.2 min for the higher dose of Glc-IPM
      was observed in the tumor. No statistically significant change of the pH value
      was observed during the examination period. The beta-nucleoside 5'-triphosphate
      (NTP)/inorganic phosphate (Pi) signal intensity ratio showed a tendency to
      decrease but without statistical significance. A rapid elimination was
      demonstrated by both the noninvasive NMR technique and the biodistribution study.
      No saturation was found in vitro for the Glc-IPM uptake, even at the
      concentration of 5 mM. Furthermore, the Glc-IPM uptake was not inhibited by the
      presence of 2-deoxyglucose and vice versa. The data show that the
      pharmacokinetics of Glc-IPM in the tumor can be followed in vivo by 31P NMR. The
      results presented are evidence for diffusion as the transport mechanism for Glc
      IPM in this tumor model. However, the better visualization of Glc-IPM as compared
      to ifosfamide may be due to metabolic trapping of a negatively charged metabolite
      after deglycosylation.

PMID- 9581608
TI  - A new multiple quantum filter design procedure for use on strongly coupled spin
      systems found in vivo: its application to glutamate.
AB  - A numerical procedure is outlined that is appropriate for the design of multiple
      quantum filter sequences targeted for the strongly coupled, multiple spin systems
      that occur in metabolites present in brain. The procedure uses numerical methods
      of solution of the density matrix equations, first, to establish the most
      appropriate resonance to target with the filter; second, to provide contour plots
      of a performance index of the filter in terms of critical sequence parameters;
      and third, to produce the response signals of the target and the background
      metabolites to the optimized filter. The procedure is exemplified for the AMNPQ
      spin system of the amino acid glutamate at a field strength of 3 T. The 2.3 ppm
      peak of the PQ multiplet of glutamate was identified as the target resonance, and
      the performance of the filter so derived was evaluated experimentally on phantom
      solutions and in human brain. These experiments clearly demonstrate that a
      linewidth of <or=4 Hz is required for full resolution of glutamate from glutamine
      at 3 T using this double quantum filter. Nevertheless, even at a linewidth of
      approximately 7 Hz in vivo, the 2.3 ppm peak of glutamate dominates the filter
      response and thereby removes a significant cause of uncertainty in measuring
      changes in glutamate by eliminating most of the background observed in unedited
      spectra obtained using PRESS or STEAM.

PMID- 9581609
TI  - Influence of aging or left ventricular hypertrophy on the human heart: contents
      of phosphorus metabolites measured by 31P MRS.
AB  - Although both aging and hypertrophy are extremely important factors for cardiac
      performance, their influence on cardiac metabolism, especially that of high
      energy phosphates, has not been fully elucidated as yet. Quantitative
      measurements of high-energy phosphates were attempted by comparing myocardial 31P
      NMR spectra with an external reference using depth-resolved surface-coil
      spectroscopy. The voxel size of the region of interest (ROI) was disk-shaped with
      15-cm diameter and 25-mm thickness, but the left ventricular weight actually
      involved in the ROI was estimated to be between 22 and 66 g using MRI. Myocardial
      phosphocreatine (PCr) content and adenosine triphosphate (ATP) content for the 30
      normal volunteers showed significant age dependence since both decreased in
      relation to increasing age. Myocardial PCr content and ATP content in patients
      with hypertension did not differ significantly from the age-matched control
      group. PCr content (6.1 +/- 2.2 micromol/g wet tissue, n = 10) and ATP content
      (4.1 +/- 1.3 micromol/g wet tissue) in patients with hypertrophic cardiomyopathy
      were less than the age-matched control group (n = 15; PCr: 9.7 +/- 2.5 micromol/g
      wet tissue, P < 0.01; ATP: 6.4 +/- 1.8 micromol/g wet tissue, P < 0.05),
      respectively. These results indicate that quantitative 31P MRS may be valuable in
      the assessment of changes in high-energy phosphate metabolism caused by aging or
      hypertrophy.

PMID- 9581610
TI  - Recovery of the rodent brain after cardiac arrest: a functional MRI study.
AB  - Recovery of the cerebral cortex after 10 min of cardiac arrest was studied in rat
      using noninvasive MRI techniques. The apparent diffusion coefficient (ADC) of
      brain water was imaged to document reversal of the metabolic impairment.
      Perfusion-weighted imaging and blood oxygen level dependent (BOLD) imaging were
      performed to assess functional recovery. To this purpose, rats were anesthetized
      with alpha-chloralose, and somatosensory cortex was activated by electrical
      stimulation of the contralateral forepaw. In sham-operated controls, cortical ADC
      was 862 +/- 10 microm2/s, and stimulation of forepaw led to a focal increase of
      signal intensity in somatosensory cortex by 71 +/- 22% in perfusion-weighted
      images and by 6 +/- 1% in BOLD images. One hour after successful resuscitation
      following 10 min of cardiac arrest, ADC did not differ from control but
      functional activation was completely suppressed. After 3 hours of reperfusion,
      functional activity began to reappear but the recovery of the BOLD signal
      progressed faster than that of the perfusion-weighted signal. The differences in
      the recovery of ADC, BOLD, and perfusion imaging are related to differences
      between metabolic and functional recovery on one hand and between blood flow and
      oxygen extraction on the other. The combination of these MRI methods thus
      provides detailed qualitative information about the progression of brain recovery
      after transient circulatory arrest.

PMID- 9581611
TI  - Quantitative assessment of bone marrow hematopoiesis using parametric magnetic
      resonance imaging.
AB  - Spatial maps of the percentage cellularity in pelvic bone marrow were calculated
      at a resolution of 15.6 mm3 from six volunteers and 10 patients treated for
      documented hematologic disease using a three-point Dixon MRI pulse sequence. The
      percentage cellularity calculation was aided by analyzing a two-dimensional
      feature space consisting of the apparent water fraction (Wa), and the T2
      relaxation time of water (T2w). An extracellular water fraction was assigned to
      each voxel on the basis of a two-component T2w algorithm. In six cases, the
      method was compared to results obtained from core biopsies or aspirates of the
      posterior iliac crest. The results indicate that segmentation schemes that
      combine high-quality phase-contrast imaging with nuclear relaxation time
      measurements can potentially identify the true fractional marrow volume occupied
      by hematopoietic elements in a variety of clinical situations.

PMID- 9581612
TI  - Characterization of and correction for eddy current artifacts in echo planar
      diffusion imaging.
AB  - Magnetic resonance diffusion imaging is potentially an important tool for the
      noninvasive characterization of normal and pathological tissue. The technique,
      however, is prone to a number of artifacts that can severely affect its ability
      to provide clinically useful information. In this study, the problem of eddy
      current-induced geometric distortions that occur in diffusion images acquired
      with echo planar sequences was addressed. These geometric distortions produce
      artifacts in computed maps of diffusion parameters and are caused by
      misalignments in the individual diffusion-weighted images that comprise the
      diffusion data set. A new approach is presented to characterize and calibrate the
      eddy current effects, enabling the eddy current distortions to be corrected in
      sets of interleaved (or snapshot) echo planar diffusion images. Correction is
      achieved by acquiring one-dimensional field maps in the read and phase encode
      direction for each slice and each diffusion step. The method is then demonstrated
      through the correction of distortions in diffusion images of the human brain. It
      is shown that by using the eddy current correction scheme outlined, the eddy
      current-induced artifacts in the diffusion-weighted images are almost completely
      eliminated. In addition, there is a significant improvement in the quality of the
      resulting diffusion tensor maps.

PMID- 9581613
TI  - Analysis of subcutaneous angiogenesis by gradient echo magnetic resonance
      imaging.
AB  - The goal of this study was to develop an experimental method for noninvasive
      analysis of angiogenesis, namely the sprouting of capillaries from existing blood
      vessels. Angiogenesis was assayed in the subcutaneous vasculature of nude mice in
      a region of 3 x 3 cm that included in its center a defined angiogenic stimulus.
      Angiogenic stimuli included agarose beads containing angiogenic growth factors,
      multicellular tumor spheroids, and dermal incisions. Highly significant
      correlation (r = 0.905, P = 0.0001) was found between the apparent vessel density
      determined by gradient echo MRI and the density of blood-containing vessels
      determined postmortem. The functionality of the neovasculature was demonstrated
      in mice breathing alternatingly carbogen or 95% air/5% CO2. Large signal
      enhancement with carbogen breathing corresponded to regions of high vessel
      density. The assay reported here can be applied for the study of dermal wound
      healing, primary vascularization of subcutaneous implants, and for measuring the
      activity of angiogenic and antiangiogenic agents.

PMID- 9581614
TI  - Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin
      labeling.
AB  - A method is presented for multislice measurements of quantitative cerebral
      perfusion based on magnetic labeling of arterial spins. The method combines a
      pulsed arterial inversion, known as the FAIR (Flow-sensitive Alternating
      Inversion Recovery) experiment, with a fast spiral scan image acquisition. The
      short duration (22 ms) of the spiral data collection allows simultaneous
      measurement of up to 10 slices per labeling period, thus dramatically increasing
      efficiency compared to current single slice acquisition protocols. Investigation
      of labeling efficiency, suppression of unwanted signals from stationary as well
      as intraarterial spins, and the FAIR signal change as a function of inversion
      delay are presented. The assessment of quantitative cerebral blood flow (CBF)
      with the new technique is demonstrated and shown to require measurement of
      arterial transit time as well as suppression of intraarterial spin signals. CBF
      values measured on normal volunteers are consistent with results obtained from
      H2O15 positron emission tomography (PET) studies and other radioactive tracer
      approaches. In addition, the new method allows detection of activation-related
      perfusion changes in a finger-tapping experiment, with locations of activation
      corresponding well to those observed with blood oxygen level dependent (BOLD)
      fMRI.

PMID- 9581615
TI  - Three-dimensional coronary MR angiography using zonal echo planar imaging.
AB  - Using an adapted two-dimensional spatially selective RF excitation scheme, a
      novel yet practical three-dimensional (3D) zonal echo-planar imaging technique
      for MR coronary angiography has been developed. The robustness of the technique
      compared with the two-dimensional (2D) segmented fast low angle shot (FLASH)
      method was evaluated using the right coronary artery images of 16 asymptomatic
      volunteers with a 0.5-T mobile scanner. Each 3D acquisition required multiple
      breath-holds, and real-time navigator echoes were used to ensure consistent
      breath-holding. Advantages of the technique include an improved signal-to-noise
      ratio, clearer depiction of tortuous coronary vessels due to decreased partial
      volume effects, and reduced motion blurring by the use of a short echo-planar
      readout.

PMID- 9581616
TI  - An MR-based technique for quantifying the deformation of articular cartilage
      during mechanical loading in an intact cadaver joint.
AB  - The objective of this study was to develop an MR-based technique for quantifying
      the deformation of articular cartilage during mechanical loading in an intact
      cadaver joint at high spatial and temporal resolution. A nonmetallic pressure
      device was constructed for applying loads of >1000 N to a femoro-patellar
      articulation within an extremity coil of a clinical 1.5 T MRI scanner. Digital
      image processing methods were used to determine the location- and time-dependent
      cartilage deformation in consecutive 2D fat-suppressed FLASH images.
      Additionally, three-dimensional reconstruction of the cartilage was performed
      from 3D fat-suppressed FLASH image data. During the first 10 min of static
      compression, thickness changes between 10 and 30% were observed. Thickness
      changes greater than 50% and volume changes of 20% were recorded after 3 h. The
      technique permits analysis of the load and time-dependent mechanical behavior of
      articular cartilage in its natural environment.

PMID- 9581617
TI  - Fast imaging of phosphocreatine using a RARE pulse sequence.
AB  - A technique is described for acquiring phosphocreatine (PCr) images of skeletal
      muscle using a rapid acquisition with relaxation enhancement (RARE) pulse
      sequence. All of the phosphorus metabolites other than PCr are forced to dephase
      within the first few echoes, whereas the Carr-Purcell Meiboom-Gill (CPMG) pulse
      sequence maintains a high PCr signal long enough to acquire 64 echoes in a single
      shot. Axial PCr images of a human forearm with a signal-to-noise ratio of 9 were
      acquired in 2 min. The effect of the refocusing pulse section profile on the
      ratio of desired to undesired metabolite signal is demonstrated.

PMID- 9581618
TI  - Flow cytometric analysis of CD3/TCR complex, zinc, and glucocorticoid-mediated
      regulation of apoptosis and cell cycle distribution in thymocytes from old mice.
AB  - Apoptosis represents the main mechanism involved in the intrathymic cell
      selection. The involution and atrophy of the thymic gland during aging has been
      associated with an altered representation of thymocyte subsets and particularly
      of CD4+CD8+ double-positive (DP) thymocytes, i.e., the cell population mainly
      involved in thymocyte selection. The aim of the present study was to evaluate the
      responsiveness of thymocytes from old mice to factors regulating the apoptotic
      cell death, such as antibodies to CD3/T cell receptor complex, zinc, and
      dexamethasone (DEX). Balb/c mice were used at the ages of 2 months (young), 21-22
      months (old), and 24-26 months (very old). Thymocytes from these mice were
      incubated overnight with anti-CD3 monoclonal antibody (8 microg/ml), Zn2+ (150
      microM), or DEX (10[-7] M) and then analysed for number of apoptotic nuclei, cell
      cycle phase, and phenotype by flow cytometry. A significant decrease of both the
      total number and the proportion of DP thymocytes was present in old and very old
      mice in comparison with young animals. Antibodies to CD3 antigen induced
      thymocyte apoptosis in both young and old mice. The stimulation of the CD3/TCR
      complex was more effective in giving apoptosis in very-old than in old and young
      mice. An impairment of the inhibiting effect of zinc on apoptosis induced by
      either serum deprivation or DEX was found in old and very old mice, whereas zinc
      was less effective in inhibiting CD3-induced apoptosis only in very old animals.
      Reduced DEX-induced apoptosis was also present in old age; this effect was more
      evident in very old than in old mice. Thymocyte apoptosis in old mice required
      protein synthesis being blocked with cycloheximide. Apoptosis was exerted on
      thymocytes in a specific cell cycle phase, i.e., on G0/G1 phase cells. Anti-CD3
      antibodies, Zn2+, or DEX regulated apoptosis by modulating the proportion of DP
      thymocytes. The results demonstrate an altered in vitro responsiveness of
      thymocytes from old and very old mice to factors regulating apoptosis and suggest
      further investigations to determine if this altered responsiveness is associated
      with increased apoptosis of thymocyte populations occurring with increasing age.

PMID- 9581619
TI  - Comparison of flow cytometric and manual bone marrow differentials in Wistar
      rats.
AB  - Preclinical drug trials frequently require the evaluation of animal bone marrow,
      a time-consuming process requiring the skills of a highly trained hematologist.
      In the present study, a flow cytometric technique was developed that could
      effectively replace the need for manual bone marrow differentials in rats.
      Peroxidase activity, measured indirectly with 2'7'-dichlorofluorescein, was
      coupled with the use of species-specific T- and B-lymphocyte antibodies and cell
      size to produce a flow cytometric analysis of rat bone marrow. Accurate
      identification of lymphocyte, proliferating and maturing erythroid and myeloid,
      and megakaryocyte populations was confirmed by cell sorting. Flow cytometry
      yielded differentials that were indistinguishable from manual differentials and
      published reference ranges. Enumeration of lymphocyte numbers with monoclonal
      markers is a key advantage of flow cytometric differentials because
      misidentification of lymphocytes in poorly prepared or stained bone marrow smears
      is a common problem. The most apparent advantage is increased throughput and
      reproducibility. Operator training for analysis using flow cytometry can be
      readily accomplished within a few days as opposed to the extensive training
      required for individuals performing manual bone marrow differentials. This
      methodology provides a high-volume, rapid, and relatively low-cost tool for the
      reliable evaluation of rat bone marrow differentials that has been heretofore
      unavailable.

PMID- 9581620
TI  - Flow cytometric evaluation of bone marrow differentials in rats with
      pharmacologically induced hematologic abnormalities.
AB  - Previously, flow cytometric determination of peroxidase activity, cell size, and
      reactivity to lymphocyte antibodies were used to produce bone marrow
      differentials in untreated rats. In the present study, abnormal hematologic
      profiles were induced with erythropoietin (EPO), recombinant murine stem cell
      factor (rm-SCF), granulocyte-macrophage stimulating factor (GM-CSF), and
      cyclophosphamide (CP). Manual and flow cytometric data showed comparable levels
      of erythroid and myeloid hyperplasia in EPO- and rm-SCF/GM-CSF-treated animals,
      respectively. In CP-treated animals, flow cytometric data revealed significant
      decreases in cellularity at concentrations of CP > or = 5 mg/kg. In contrast, 20
      mg/kg CP were necessary to induce microscopically apparent hypoplasia in
      histologic bone sections, showing that the automated methodology was a more
      sensitive indicator of bone marrow hypocellularity than was the more conventional
      manual method. Megakaryocyte counts were consistently higher by flow cytometer
      than by manual counts performed on cytocentrifuge preparations made from the same
      cell suspensions but were similar to megakaryocyte counts performed on histologic
      sections of femur, indicating that the automated methodology produced a more
      accurate reflection of true megakaryocyte numbers. Induction of hematologic
      abnormalities in the present study showed that manual bone marrow differentials
      can be replaced with the more efficient and reliable flow cytometric method in
      most preclinical toxicology studies.

PMID- 9581621
TI  - Optimization of a flow cytometric method for the simultaneous measurement of cell
      surface antigen, DNA content, and in vitro BrdUrd incorporation into normal and
      malignant hematopoietic cells.
AB  - We have designed an assay for the simultaneous measurement of cell surface
      phenotype, S-phase fraction, and DNA content by single laser instrumentation for
      the purpose of determining the labeling index (LI), duration of S-phase (Ts), and
      the potential doubling time (Tpot) of leukocyte subpopulations. The procedure was
      optimized with regard to: mode of bromodeoxyuridine (BrdUrd) incorporation,
      selection of suitable leukocyte differentiation antigens (LDAs) as well as PE
      conjugated monoclonal antibodies (MoAbs) against myeloid cells, overnight
      permeabilization and fixation (paraformaldehyde 1% and 0.05% Nonidet P40), DNase
      I treatment (250 Kunitz units), concentration of FITC-conjugated anti-BrdUrd MoAb
      (dilution 1:5), and DNA staining with 7-amino-actinomycin (7-AAD) (10 microg/ml).
      We validated this assay by measuring LI, Ts, and Tpot repeatedly in four leukemic
      cell lines and found these to be stable (coefficients of variation (CV): 0.06,
      0.13, and 0.08, respectively). Finally, we employed the assay on different
      leukocyte preparations from normal donors (including purified CD34 + cells) and
      patients with malignant myeloid disorders, and we concluded that it will yield
      valuable data regarding the cell cycle kinetics of subsets of leukocytes in
      heterogeneous mixtures of hematopoietic cells.

PMID- 9581622
TI  - Analysis of in vitro lymphocyte adhesion and transendothelial migration by
      fluorescent-beads-based flow cytometric cell counting.
AB  - In this report, we describe a new and simple method for flow cytometric
      quantitation of lymphocyte numbers in lymphocyte-endothelial adhesion/
      transendothelial migration assays. The method exploits fluorescent flow cytometer
      alignment beads as a counting reference. Known amounts of beads are added to
      samples with unknown lymphocyte numbers. Lymphocytes and a preset number of
      fluorescent beads are simultaneously analyzed. The total number of cells present
      in the sample can be subsequently calculated from the fixed ratio of added to
      analyzed fluorescent beads. Using this fluorescent-beads-based flow cytometric
      cell counting of lymphocyte numbers in adhesion/migration assays, labeling of
      cells and other time-consuming calibration procedures are not required and
      analysis time is short. Furthermore, we demonstrate that this cell counting
      method can be combined with concurrent single- or double-label fluorescence flow
      cytometric phenotyping of adherent and migrated lymphocytes. The method was
      applied to the in vitro study of the effects of lymphocyte activation status and
      binding of bispecific antibody (directed against CD3 x tumor cell-associated
      antigen) on lymphocyte adhesion and transendothelial migration.

PMID- 9581623
TI  - Comparative analysis of apoptosis measured by Hoechst and flow cytometry in non
      Hodgkin's lymphomas.
AB  - Fine-needle samples of 75 non-Hodgkin's lymphomas were investigated for apoptosis
      immediately and after 24 h of culture after in vitro irradiation (2 Gy, 10 Gy,
      and nonirradiated controls). Apoptotic cells were simultaneously quantified by
      fluorescence microscopic enumeration of apoptotic cells using Hoechst 33342
      staining, and by flow cytometric detection of sub-G1 peak cells. The
      nonirradiated controls showed a similar mean percent apoptotic cells using both
      methods, analyzed immediately (9% by morphology vs. 10% by flow) or after 24 h of
      culture (40% by morphology vs. 41% by flow). In the irradiated samples, the mean
      percent apoptotic cells quantified by morphology was higher than by flow
      cytometry (64% by morphology vs. 55% by flow after 2 Gy irradiation, and 71% vs.
      58% after 10 Gy). The results of the two methods were correlated, although large
      differences were seen between the techniques in individual tumors. In our system,
      flow cytometric sub-G1 peak analysis appears to underestimate apoptosis. Of these
      two methods, we find the Hoechst morphology method to be more reliable for
      quantitation of apoptosis utilizing fresh fine-needle sample material, in that
      discrimination of apoptotic cells from debris is easier and that both early and
      late apoptotic cells are detectable.

PMID- 9581624
TI  - Relationship between morphometric analysis of nucleolar organizer regions and
      cell proliferation in acute leukemias.
AB  - Silver-stained nucleolar organizer regions in interphase cells have been widely
      studied as a cell kinetic parameter in different tissues. Many different
      approaches have been used for this evaluation, often leading to conflicting
      results. The aim of our study was to analyze several commonly used AgNOR
      parameters in bone marrow smears of 32 newly diagnosed cases of acute leukemia:
      number of clusters and dots, percentage of cells with one cluster (cells in a
      long G1 phase), total and percentage of silver-stained area per nucleus, mean
      size of AgNORs, and the Ruschoff index. These parameters were compared with the
      in vitro incorporation of bromodeoxyuridine (BrdU). A significant correlation was
      found between the BrdU index and the mean number of clusters (r = 0.60), dots (r
      = 0.60), percentage of cells with one cluster (r = -0.63), as well as with the
      mean size of AgNORs (r = -0.63) and the Ruschoff index (r = 0.72). In a factor
      analysis, total AgNOR area, its percentage of nuclear area, the mean AgNOR size,
      and the nuclear area formed one factor (factor of area parameters), and clusters,
      dots, the percentage of cells with one cluster, and BrdU index made another
      factor (factor of proliferation parameters). The Ruschoff index participated
      equally in both factors. Based on these data, we postulate that the number of
      clusters and dots are related to the percentage of cells in S-phase and the AgNOR
      area may be related to the cell duplication time, as has been reported in the
      literature. Mean size of AgNORs is smaller in highly proliferating cells.
      Probably the Ruschoff index is related to the percentage of cells in S-phase as
      well as to the cell duplication time, and seems to be the best AgNOR parameter
      for the global evaluation of cell kinetics in acute leukemias.

PMID- 9581625
TI  - Novel approach for simultaneous evaluation of cell phenotype, apoptosis, and cell
      cycle using multiparameter flow cytometry.
AB  - Apoptosis is a vital process for organism development and, when disrupted, can
      lead to abnormalities including cancer and autoimmune diseases. We demonstrate a
      novel multicolor flow cytometry approach for quantifying apoptosis and cell cycle
      information of phenotypically distinct populations, using less than 2 x 10(5)
      cells per sample. We used incorporation of Cy5-dUTP into DNA strand breaks by the
      terminal dUTP nucleotide end labeling (TUNEL) method to determine apoptosis,
      while cell cycle information was assessed with an ultraviolet DNA binding dye,
      DAPI. To simultaneously determine surface phenotype, we used paraformaldehyde
      fixation and a gentle permeabilization protocol combined with FITC- and PE
      labeled surface antibodies. Using these fluorochromes, and three-laser
      instrumentation, we quantified apoptosis and cell cycle phase in lymphocyte
      subpopulations from heterogeneous human and murine cell sources, subjected to
      various culture conditions. Further, we used this method to detect divergent
      rates of apoptosis in a human, heterogeneous lymphocyte tumor population,
      demonstrating a potential application for clinical and/or research settings.
      Thus, we describe a six-parameter, four-color flow cytometry approach for
      evaluating apoptosis and cell cycle with dual surface labels. This method may
      also be useful as a generalized scheme to assess simultaneously two intracellular
      targets in a mixed cell population.

PMID- 9581626
TI  - Quantification of neurotoxicity and identification of cellular subsets in a three
      dimensional brain model.
AB  - Imaging of cells in a large intact three-dimensional tissue remains difficult.
      Quantification and identification of cell damage in a mixed culture system has
      been limited by the inability of fluorescent probes to discriminate types of
      cellular death and penetrate tissue more that 100 microm thick. We have
      investigated several probes in combination with neural cell-specific antibodies
      to quantify cell damage in the presence of several toxins. Acridine orange and
      ethidium bromide were excellent for determination of cell viability, death by
      necrosis, or apoptosis in thick brain tissue aggregates. Calcein and ethidium
      homodimer were effective on live/ dead stains, and the Syto dyes 11 and 13 worked
      well for quantification of all cells in the brain aggregate model. By using these
      combinations of dyes in conjunction with confocal microscopy, we were able to
      quantify neural cell damage without disrupting the three-dimensional environment.

PMID- 9581627
TI  - Birds' eye view: a decade of perspectives.

PMID- 9581628
TI  - Heritable variation and mutagenesis at early International Congresses of
      Genetics.

PMID- 9581630
TI  - Behavioral effects of prenatal alcohol exposure: a Borchard Foundation symposium.
      Introduction to the symposium.

PMID- 9581631
TI  - A review of the neurobehavioral deficits in children with fetal alcohol syndrome
      or prenatal exposure to alcohol.
AB  - Fetal alcohol syndrome is a devastating developmental disorder caused by prenatal
      exposure to high amounts of alcohol. In addition to structural abnormalities and
      growth deficits, fetal alcohol syndrome is associated with a broad spectrum of
      neurobehavioral anomalies. This paper reviews the behavioral and cognitive
      effects of prenatal alcohol exposure. More than 20 years of research are
      discussed, with a focus on IQ, activity, attention, learning, memory, language,
      motor, and visuospatial abilities in children prenatally exposed to varying
      amounts of alcohol, including those with fetal alcohol syndrome.

PMID- 9581629
TI  - Functions of the high mobility group protein, Abf2p, in mitochondrial DNA
      segregation, recombination and copy number in Saccharomyces cerevisiae.
AB  - Previous studies have established that the mitochondrial high mobility group
      (HMG) protein, Abf2p, of Saccharomyces cerevisiae influences the stability of
      wild-type (rho+) mitochondrial DNA (mtDNA) and plays an important role in mtDNA
      organization. Here we report new functions for Abf2p in mtDNA transactions. We
      find that in homozygous deltaabf2 crosses, the pattern of sorting of mtDNA and
      mitochondrial matrix protein is altered, and mtDNA recombination is suppressed
      relative to homozygous ABF2 crosses. Although Abf2p is known to be required for
      the maintenance of mtDNA in rho+ cells growing on rich dextrose medium, we find
      that it is not required for the maintenance of mtDNA in p cells grown on the same
      medium. The content of both rho+ and rho- mtDNAs is increased in cells by 50-150%
      by moderate (two- to threefold) increases in the ABF2 copy number, suggesting
      that Abf2p plays a role in mtDNA copy control. Overproduction of Abf2p by > or =
      10-fold from an ABF2 gene placed under control of the GAL1 promoter, however,
      leads to a rapid loss of rho+ mtDNA and a quantitative conversion of rho+ cells
      to petites within two to four generations after a shift of the culture from
      glucose to galactose medium. Overexpression of Abf2p in rho- cells also leads to
      a loss of mtDNA, but at a slower rate than was observed for rho+ cells. The mtDNA
      instability phenotype is related to the DNA-binding properties of Abf2p because a
      mutant Abf2p that contains mutations in residues of both HMG box domains known to
      affect DNA binding in vitro, and that binds poorly to mtDNA in vivo, complements
      deltaabf2 cells only weakly and greatly lessens the effect of overproduction on
      mtDNA instability. In vivo binding was assessed by colocalization to mtDNA of
      fusions between mutant or wild-type Abf2p and green fluorescent protein. These
      findings are discussed in the context of a model relating mtDNA copy number
      control and stability to mtDNA recombination.

PMID- 9581632
TI  - Prenatal alcohol exposure and development at preschool age: main results of a
      French study.
AB  - Very high levels of alcohol consumption during pregnancy are harmful for the
      central nervous system of the child and affect morphogenesis and growth. The aim
      of this study was to investigate the effects of moderate prenatal alcohol
      exposure on development at preschool age in a longitudinal study. Pregnant women
      were interviewed on their alcohol consumption during pregnancy at their first
      visit to the maternity hospital of Roubaix, France. The development of their 160
      children was assessed at the age of 4 1/2. Multiple regression analyses indicated
      that consumption of 1.5 oz of absolute alcohol (approximately 3 drinks) or more
      during pregnancy was significantly related to a decrease of 7 points on the
      general cognitive index of the McCarthy scales, after controlling for
      confounders. This level of consumption was also related to a higher score on
      minor neurological anomalies, a lower height of the child, and a higher score on
      facial features. This level of 1.5 oz of absolute alcohol/day should not be
      interpreted as a biological threshold, because the study does not allow
      conclusions to be drawn regarding the effects of lower levels of alcohol
      consumption. Alcohol consumption during pregnancy can affect the development of
      the child, at levels well below those associated with fetal alcohol syndrome.

PMID- 9581633
TI  - Neuroanatomical and neurophysiological mechanisms involved in central nervous
      system dysfunctions induced by prenatal alcohol exposure.
AB  - One of the most severe consequences of maternal ethanol consumption is the damage
      to the developing central nervous system, which is manifested by long-term
      cognitive and behavioral deficits in the offspring. Prenatal exposure to ethanol
      affects many crucial neurochemical and cellular components of the developing
      brain. Ethanol interferes with all of the stages of brain development, and the
      severity of the damage depends on the amount of ethanol intake and level of
      exposure. Experimental observations also indicate that the toxic effects of
      ethanol are not uniform: some brain regions are more affected than others and,
      even within a given region, some cell populations are more vulnerable than
      others. The neocortex, the hippocampus, and the cerebellum are the regions in
      which the neurotoxic effects of ethanol have been associated with the behavioral
      deficits. At the cellular level, ethanol disrupts basic developmental processes,
      including interference with division and proliferation, cell growth, and
      differentiation and the migration of maturing cells. Alterations in astroglia
      development and in neuronal-glial interactions may also influence the development
      of the nervous system. An impairment of several neurotransmitter systems and/or
      their receptors, as well as changes in the endocrine environment during brain
      development, are also important factors involved in the behavioral dysfunctions
      observed after prenatal ethanol exposure. Finally, some molecular mechanisms of
      ethanol-induced behavioral dysfunctions will be discussed.

PMID- 9581635
TI  - Neuropsychological disorders in children exposed to alcohol during pregnancy: a
      follow-up study of 24 children to alcoholic mothers in Goteborg, Sweden.
AB  - This paper reports on a follow-up study of 24 children to alcoholic mothers at 12
      to 14 years of age. The mothers were offered support to help them stop drinking
      during pregnancy and was grouped to time point of instituted sobriety. Six of the
      24 children attended a school for the mentally retarded, and 11 children had some
      kind of special education. The children have difficulties in mathematics, logical
      conclusions, visual perception, spatial relations, and short-range
      memory/attention. Sixteen children were in fostercare. A clear correlation
      between the occurrence and severity of neuropsychological problems and the degree
      of alcohol exposure in utero was found.

PMID- 9581634
TI  - Specificity of neurobehavioral outcomes associated with prenatal alcohol
      exposure.
AB  - A current issue in alcohol research is whether a "neurobehavioral profile" can be
      identified for prenatal alcohol exposure, even when dysmorphic features are not
      present, or whether comparable neurobehavioral deficits are detected when damage
      is incurred by numerous neurotoxicants to which the fetus is exposed during a
      common developmental period. Failure to detect such differences may, in part, be
      an artifact of the global developmental tests used to assess outcome. Cognitive
      effects of prenatal exposure to three different teratogens [polychlorinated
      biphenyls (PCBs), alcohol, and cocaine] are examined to determine whether
      exposure to each substance results in a common or different pattern of impairment
      on the same set of newer, more narrow band infant tests. Comparison of findings
      from three independent cohorts indicate that PCB exposure was related to poorer
      recognition memory on the Fagan Test of Infant Intelligence (FTII) in Michigan
      infants exposed prenatally to PCB-contaminated fish, whereas prenatal alcohol
      exposure was unrelated to recognition memory but to slower processing speed on a
      new FTII measure and slower reaction time on Haith's Visual Expectancy Paradigm
      (VExP) in our Detroit alcohol-exposed infants. Preliminary findings from a new
      study of infants recently born to Taiwanese women accidentally contaminated with
      sizable amounts of PCBs indicate recognition memory deficits, confirming our
      Michigan findings, but no processing speed effects on the FTII. Recent findings
      from our Detroit cohort suggest that heavy prenatal cocaine exposure is related
      to poorer recognition memory on the FTII, but faster reaction times on the VExP,
      a pattern different from that seen for either PCBs or alcohol.

PMID- 9581636
TI  - A fetal alcohol behavior scale.
AB  - This research aimed to develop a Fetal Alcohol Behavior Scale (FABS) that
      describes the behavioral essence of fetal alcohol syndrome (FAS) and fetal
      alcohol effects (FAE), regardless of age, race, sex, and IQ. Using a reference
      sample of 472 diagnosed patients with FAS or FAE, ages 2 to 51, five studies are
      described. The FABS demonstrates high item-to-scale reliability (Cronbach's alpha
      = 0.91) and good test-retest reliability (r = 0.69) over an average interval of 5
      years. It identifies many of the subjects with known or presumed prenatal alcohol
      exposure in detection studies using both prison and general samples. FABS scores
      also predict dependent living among adult patients with FAS/FAE. The FABS is
      uncorrelated with IQ, sex, age, race, and diagnosis (FAS versus FAE). We outline
      areas of further work to define the specificity and utility of this FABS.

PMID- 9581637
TI  - Long-term outcome of children with fetal alcohol syndrome: psychopathology,
      behavior, and intelligence.
AB  - Within an interdisciplinary research project, the long-term outcome of children
      with fetal alcohol syndrome was studied. Methods for the assessment of
      psychopathology, behavior, and intelligence included psychiatric interviews,
      behavior checklists for parents and teachers, and intelligence tests. The
      children were assessed during preschool age, early school age (6 to 12 years),
      and late school age (> or =13 years). An excess of psychopathology, (including
      hyperkinetic disorders, emotional disorders, sleep disorders, and abnormal habits
      and stereotypes) with a strong persistence over time was found. Cognitive
      functioning was marked by a large proportion of mentally retarded children and
      also did not change considerably over time. This long-term outcome study reflects
      the handicapping effects of fetal alcohol syndrome.

PMID- 9581638
TI  - A review of the neuroanatomical findings in children with fetal alcohol syndrome
      or prenatal exposure to alcohol.
AB  - Human and animal studies have clearly demonstrated that alcohol is both a
      physical and behavioral teratogen and that heavy prenatal alcohol exposure can
      lead to a distinct pattern of birth defects termed the fetal alcohol syndrome.
      Underlying the behavioral and cognitive anomalies seen in fetal alcohol syndrome
      are alterations in brain structure and/or function. This paper reviews the
      literature examining brain anomalies attributable to prenatal alcohol exposure,
      beginning with a survey of autopsy studies and leading up to current findings
      using magnetic resonance imaging and positron emission tomography studies.
      Autopsy reports clearly illustrate the wide and devastating influence alcohol has
      on the developing brain, although for the most part no specific pattern of brain
      malformation has been identified. More recent magnetic resonance imaging studies,
      particularly when combined with quantitative analysis, have indicated that
      specific brain areas--such as the basal ganglia, the corpus callosum, and parts
      of the cerebellum--might be especially susceptible to alcohol's teratogenic
      effects. Further studies using functional brain imaging techniques may provide
      even more information about the unique effects prenatal alcohol exposure has on
      the developing brain. Discovering specific areas of the brain that are affected
      by alcohol may allow clinicians and researchers to look for patterns of
      vulnerable regions in the brain, thereby helping in the future detection of
      children who are prenatally exposed to alcohol.

PMID- 9581639
TI  - Relation of maternal age and pattern of pregnancy drinking to functionally
      significant cognitive deficit in infancy.
AB  - Prospective studies of the effects of prenatal alcohol exposure on development
      have focused primarily on the detection of subtle deficits. This study was
      designed to extend those findings by evaluating dose-response, functional
      significance, and pattern of drinking in greater detail. 480 African-American
      infants, recruited to overrepresent prenatal exposure at moderate-to-heavy
      levels, were assessed. For the five outcomes tested, nonparametric and hockey
      stick regression analyses both indicated essentially no relation between
      pregnancy drinking and developmental outcome below a median threshold of 0.5 oz
      absolute alcohol/day, with the impact of the exposure increasing gradually above
      threshold. Functional deficit was defined in terms of performance in the bottom
      10th percentile of the distribution. For four of the five outcomes tested, there
      was no increased incidence of functionally significant deficit in infants born to
      moderate-to-heavy drinking mothers <30 years old, whereas those born to older
      drinking mothers were 2 to 5 times more likely to be functionally impaired. Among
      the infants exposed above threshold, functionally significant deficits were seen
      primarily in those whose mothers averaged at least 5 drinks/occasion on an
      average of at least once/week. By contrast, a history of alcohol abuse was not
      related to functional deficit. These data suggest that efforts to reduce the
      incidence of alcohol-related functional impairment should specifically target the
      older mother who engages in intermittent heavy drinking during pregnancy.

PMID- 9581640
TI  - Free methionine supplementation limits alcohol-induced liver damage in rats.
AB  - Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has
      been shown to result in liver damage being comparable with alcohol-induced liver
      disease in man. In the present study, a striking effect of free methionine
      consumption on histological liver injury, triglyceride accumulation, and energy
      rich nucleoside content in the liver of rats with a jejunoileal bypass is
      demonstrated. The animals obtained 0, 30, and 120 mg of methionine in the control
      group and 0, 30, 120, and 240 mg in the alcohol-fed group per day and per
      kilogram of body weight for 12 weeks. Methionine was found to strongly improve
      the alcohol-induced histological changes in the liver. Triglyceride content of
      the liver was found to decrease in a dose-dependent manner with increasing
      methionine ingestion (from 255 +/- 20.7 to 49.7 +/- 6.1 micromol/g of protein in
      the control group and from 233 +/- 17.3 to 42.1 +/- 7.2 micromol/g of protein in
      the alcohol group). Hepatic adenosine triphosphate content increased
      significantly with higher methionine consumption (13.5 +/- 0.8 vs. 26.9 +/- 2.8
      micromol/g of protein in the control group and 11.9 +/- 1.4 vs. 20.5 +/- 2.5
      micromol/g of protein in the alcohol group), whereas no differences were found in
      the protein and DNA content of the liver. These results underscore the impairment
      of the transmethylation/transsulfuration pathway in the development of alcohol
      induced liver diseases.

PMID- 9581641
TI  - Effects of acute and chronic doses of naltrexone on ethanol self-administration
      in rhesus monkeys.
AB  - The effects of acute and chronic administration of intramuscular naltrexone (0.1,
      0.3, 1.0, and 3.0 mg/kg) on oral ethanol (8%) self-administration were examined.
      Naltrexone (1.0 mg/kg) effects on the self-administration of ethanol
      concentrations ranging from 0.5 to 8% (w/v) were also investigated. Rhesus
      monkeys with substantial histories of drug and ethanol drinking served as
      subjects. During daily 3-hr sessions, monkeys were presented with ethanol
      solutions, concurrently available with water, under fixed-ratio reinforcement
      schedules. Naltrexone decreased the consumption of ethanol (g/kg). Biphasic
      temporal effects were observed within sessions. Naltrexone dose-dependently
      decreased the number of ethanol deliveries by a maximum of 56% (n = 18; 3 monkeys
      x 6 sessions) during the first hour of the session. During the second and third
      hours, however, ethanol intake recovered such that maximum decreases over the 3
      hr session were approximately 27% (n = 18), and the mean decrease was 16% (n =
      18). Often marked tolerance was observed, such that the effects of acute
      naltrexone administration were greater than effects after chronic administration.
      The self-administration of low ethanol concentrations (< or =2% w/v) was
      increased in several monkeys, by up to 340%, after naltrexone pretreatment. In
      summary, the effects of naltrexone on ethanol self-administration, in drug- and
      alcohol-experienced rhesus monkeys, are not characterized by unitary decreases in
      measures of ethanol self-administration. Rather, differential naltrexone effects
      were a function of experimental parameters, including the dose and number of
      naltrexone injections, the ethanol concentration, and the time point of
      measurement.

PMID- 9581642
TI  - Comparison of local and systemic ethanol effects on extracellular dopamine
      concentration in rat nucleus accumbens by microdialysis.
AB  - To determine the site of action of systemic ethanol on dopaminergic function in
      the nucleus accumbens, we compared the effect of intraperitoneal (i.p.) and local
      administration of ethanol on interstitial dopamine concentration using
      microdialysis in freely moving rats. The i.p. administration of 1 g/kg of ethanol
      significantly increased the dialysate dopamine (DA) concentrations (approximately
      40% above basal), compared with saline treatment. The concentration-time profile
      of DA and ethanol in dialysates was similar after two ethanol injections 4 hr
      apart. Local perfusion with several ethanol concentrations showed that 510 and
      860 mM of ethanol caused a significant concentration-related increase in
      extracellular DA concentrations in the nucleus accumbens (510 mM, 28% increase;
      860 mM, 62% increase). However, lower ethanol concentrations, 170 mM or below,
      failed to change basal DA concentrations. Stimulation with high potassium (50 mM)
      in artificial cerebrospinal fluid preceding local ethanol treatment increased
      dialysate DA concentrations to 523 +/- 83% of basal levels, confirming that the
      DA terminals were responsive to pharmacological manipulation. Basal DA levels in
      dialysates were approximately 70% calcium-dependent when tested at the end of the
      local perfusion experiments. Stereological examination of the nucleus accumbens
      revealed probe-induced damage, but did not detect additional damage by local
      perfusion of ethanol. When ethanol concentrations in the DA sampling area around
      the probe are taken into account in both systemic and local administration
      experiments, this study suggests that concentrations of ethanol associated with
      moderate intoxication do not directly affect the function of DA terminals in the
      nucleus accumbens. Therefore, the systemic effects of ethanol on nucleus
      accumbens DAergic function is more likely due to an interaction with sites other
      than the nucleus accumbens.

PMID- 9581643
TI  - Alcohol-induced upregulation of plasminogen activators and fibrinolytic activity
      in cultured human endothelial cells.
AB  - Clinical studies suggest that moderate alcohol consumption may decrease the risk
      for coronary artery disease and myocardial infarction. This effect may be
      attributed, in part, to the alcohol-mediated increase in endothelial cell (EC)
      mediated fibrinolytic activity mediated by the increase in synthesis and/or
      activity of tissue-type plasminogen activators (t-PAs) and/or urokinase-type PA
      (u-PAs). To determine whether low alcohol levels (0.01 to 0.1%, v/v) induced the
      expression of these proteins, cultured human saphenous vein ECs (HSVECs) were
      preincubated in the absence/presence of ethanol for 5 to 120 min at 37 degrees C,
      washed, refed, and further incubated for 8 and 24 hr without alcohol. PA mRNA
      (reverse transcriptase-polymerase chain reaction) and secreted antigen (ELISA)
      levels were analyzed after incubation for 8 and 24 hr and the net expression of
      (sustained) endogenous PA-mediated surface-localized HSVEC fibrinolytic activity
      (plasmin generation) quantitated by activation of 125I-Glu-plasminogen after
      incubation for 24 hr. A brief 5 to 30 min preincubation (induction) of both t-PA
      and u-PA antigen increased approximately 3-fold (t-PA control, 14.2 +/- 1.7, plus
      alcohol, 25.4 +/- 5 ng/ml; u-PA control, 15 +/- 0.8, plus alcohol, 46.4 +/- 1.3
      ng/ml) and mRNA levels approximately 2-fold, as compared with controls. Increased
      PA expression was associated with a significant concomitant approximately 2-fold
      increase in surface-localized fibrinolytic activity (control, 96 +/- 2.8, plus
      alcohol, 255 +/- 42 fmol/ well). These combined results indicate that a brief
      exposure (<30 min) to low levels of alcohol can induce synthesis of EC-produced t
      PA and u-PA resulting in an increased expression of HSVEC surface-localized
      fibrinolytic activity and may account, in part, for the apparent cardioprotective
      benefit associated with moderate alcohol consumption.

PMID- 9581644
TI  - Chronic ethanol exposure impairs phosphorylation of CREB and CRE-binding activity
      in rat striatum.
AB  - This study examined influences of ethanol exposure on phosphorylation of cAMP
      response element-binding protein (CREB) and CRE-binding activity in the striatum
      of rats. The phosphorylated form of CREB increased 180% during acute
      intoxication, compared to sham conditions. After chronic ethanol exposure,
      induction of CREB phosphorylation by an acute ethanol challenge was markedly
      attenuated (50%) compared with acute ethanol exposure in the pair-fed condition.
      Gel retardation assays with oligomers encoding the rat proenkephalin CRE-1 and
      CRE-2 were performed to determine the effects of ethanol on CRE-binding activity.
      Supershift experiments demonstrated that striatal nuclear protein contains CREB
      and CEBPPbeta (CCAAT/enhancer-binding protein) and that both transcription
      factors are involved in specifically binding to the DNA sequence. Rechallenging
      rats that had been chronically exposed to ethanol with an acute ethanol challenge
      reduced the CRE/nuclear protein complexes. However, supershift analyses did not
      show that chronic ethanol exposure altered the dimerization patterns of CREB and
      CEBPbeta within the complexes. Associated with these impairments in CREB binding
      and CREB phosphorylation was a significant reduction in two CREB-modulated
      factors, proenkephalin and c-fos expression. In summary, acute ethanol exposure
      activates the phosphorylation of CREB. Neuroadaptation to chronic ethanol
      exposure includes alterations in CREB physiology that may impair genes that are
      dependent upon CREB for transcriptional activation.

PMID- 9581645
TI  - Influence of ethanol consumption on immune competence of adult animals exposed to
      ethanol in utero.
AB  - Ethanol consumption results in significant changes in the immune system of
      experimental animals and humans. Previous work by ourselves and others has
      established that in utero exposure to ethanol results in alterations in the
      immune system of the offspring that persist into adult life. The present study
      was designed to determine if prenatal exposure to ethanol results in increased
      vulnerability to the immunosuppressive effects of ethanol consumption in
      adulthood. Male and female Sprague-Dawley offspring were selected in adulthood
      from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups,
      and given either an ethanol-containing liquid diet or were pair-fed an isocaloric
      liquid diet without ethanol for 30 days. At the end of the 30-day feeding period,
      lymphocyte responses to the mitogens concanavalin A (Con A) and
      lipopolysaccharide, and to interleukin-2 (IL-2) were tested using in vitro
      assays. The results of this study support and extend previous data demonstrating
      long-term adverse effects of prenatal ethanol exposure on T-cell responses to
      mitogens, and provide further evidence that deficits seem to be more robust in
      male than in female offspring. Prenatal E males showed reduced T-lymphocyte
      proliferation to Con A and T-lymphoblast proliferation to IL-2, compared with
      their prenatal PF and C counterparts, regardless of whether they were exposed to
      the ethanol or the control diet in adulthood. In addition, T-lymphoblast
      proliferation to IL-2 was suppressed in prenatal E, compared with prenatal C,
      females exposed to control diet in adulthood. This is the first report of a
      deficit in T-cell aspects of immunity in E females, although it appears that this
      deficit may have been partially mediated by nutritional effects. A second major
      finding in this study is that consumption of ethanol diet in adulthood in itself
      had significant immunosuppressive effects on T-cell responses in both males and
      females. However, contrary to our expectation, previous exposure to ethanol in
      utero did not exacerbate the changes in immune responsiveness that were observed
      after adult ethanol consumption.

PMID- 9581646
TI  - Common quantitative trait loci for alcohol-related behaviors and CNS neurotensin
      measures: voluntary ethanol consumption.
AB  - The C57BL/6, DBA/2, and recombinant inbred (RI) strains derived from them (BxD
      RIs) are the most frequently studied mouse strains with regard to genetic
      regulation of voluntary ethanol consumption (YEC). We have studied VEC in an
      alternate genetic model provided by the LSxSS RIs. These RI strains exhibit
      phenotypic extremes in VEC comparable to the C57BL/6 and DBA/2 mice and genotype
      dependent sex differences in drinking behavior. A correlational analysis between
      various ethanol-related behaviors suggests genetic independence of VEC from high
      dose neurosensitivity (sleep time), acute ethanol tolerance, hypothermia, and low
      dose locomotor activity. A search for quantitative trait loci identified a number
      of putative quantitative trait loci (QTL), three of which are identical to those
      previously reported for 10% ethanol drinking in the BxD RIs. We also find a
      significant correlation between low-affinity neurotensin receptor densities
      (NTRL) in the frontal cortex and VEC, and more common QTL between these two
      phenotypes than expected by chance. This suggests a role for frontal cortex NTRL
      in regulating voluntary ethanol intake.

PMID- 9581647
TI  - Ethanol disrupts carbamylcholine-stimulated release of arachidonic acid from
      Chinese hamster ovary cells expressing different subtypes of human muscarinic
      receptor.
AB  - Ethanol disrupts signal transduction mediated by a variety of G-protein coupled
      receptors. We examined the effects of ethanol on arachidonic acid release
      mediated by muscarinic acetylcholine receptors. Chinese hamster ovary (CHO) cells
      transfected with the different subtypes of human muscarinic receptors (M1 to M5)
      were incubated with [3H]arachidonic acid ([3H]AA) for 18 hr, washed, and exposed
      to the cholinergic agonist carbamylcholine for 15 min. Carbamylcholine induced
      [3H]AA release from CHO cells expressing M1, M3, or M5, but not M2 or M4,
      muscarinic receptors. Dose response curves revealed that carbamylcholine
      stimulated [3H]AA release by up to 12-fold with an ECo of approximately 0.4
      microM; maximal responses were obtained with 10 microM carbamylcholine. Exposure
      of M1-, M3-, or M5-expressing cells to ethanol for 5 min before stimulating with
      carbamylcholine reduced [3H]AA release by 40 to 65%; 50% of the maximal
      inhibition was obtained with an ethanol concentration of 30 to 50 mM. Ethanol did
      not affect basal [3H]AA release measured in the absence of carbamylcholine. Dose
      response curves suggest that ethanol acts as a noncompetitive inhibitor of
      muscarinic receptor-induced [3H]AA release insofar as maximal [3H]AA release was
      depressed in the presence of ethanol with no apparent change in the EC50 for
      stimulation by carbamylcholine. Exposure of CHO cells to 38 mM ethanol for 48 hr
      increased [3H]AA release induced by carbamylcholine without affecting basal
      [3H]AA release or altering the EC50 for carbamylcholine. These results indicate
      that ethanol acutely inhibits muscarinic receptor signaling through the
      arachidonic acid pathway in a noncompetitive manner, but chronically enhances
      muscarinic signaling through the same pathway.

PMID- 9581648
TI  - Differential effects of ethanol on memory in adolescent and adult rats.
AB  - Previous studies have shown that ethanol inhibits memory-related synaptic
      activity and plasticity more potently in hippocampal slices from immature rats,
      compared with those taken from adults. We therefore hypothesized that ethanol
      would more potently attenuate the acquisition of spatial memory in adolescents,
      compared with adult rats. Adult (65 days of age) and adolescent (30 days of age)
      male rats were given five daily trials on a spatial memory task in a Morris Water
      Maze. The animals from each age group were subdivided into three subgroups. Each
      day, thirty minutes before training, the animals in each subgroup were given an
      intraperitoneal injection of 1.0 g/kg of ethanol, 2.0 g/kg of ethanol, or the
      saline vehicle. Training continued daily until the control animals had reached a
      performance criterion. Ethanol treatment significantly impaired spatial memory
      acquisition in the adolescent rats, but did not impair acquisition in adult rats.
      A separate experiment with identical treatment groups showed that ethanol did not
      impair acquisition of a nonspatial memory task in the water maze in animals from
      either age group. These experiments show that the acquisition of spatial, but not
      nonspatial, memory is more potently impaired by ethanol in adolescent animals,
      compared with adults.

PMID- 9581649
TI  - Serum and muscle levels of alpha-tocopherol, ascorbic acid, and retinol are
      normal in chronic alcoholic myopathy.
AB  - Some authors have suggested a possible loss of antioxidant factors in alcoholic
      skeletal myopathy. To assess the relationship between ethanol consumption and
      serum and muscle levels of alpha-tocopherol, ascorbic acid, and retinol in
      chronic alcoholics with and without skeletal myopathy, a prospective cross
      sectional study was performed in the Alcohol Unit of a 1000-bed university
      hospital. Twenty-five chronic male alcoholic patients (10 with skeletal myopathy)
      and 15 male controls of similar age were included. Evaluation of daily and
      lifetime ethanol consumption, assessment of anthropometric and protein
      nutritional parameters, and open biopsy of the left deltoid muscle were
      performed, as well as determinations of serum and muscle levels of retinol, alpha
      tocopherol, and ascorbic acid by HPLC analysis. Ten of the 25 chronic alcoholic
      patients presented histological criteria of skeletal myopathy. Four alcoholics
      presented caloric malnutrition and three protein malnutrition. All of the muscle
      biopsies of the control group were entirely normal, as were their nutritional
      studies. The serum and muscular levels of alpha-tocopherol, ascorbic acid, and
      retinol were normal and were similar in both alcoholics and controls. Except for
      serum retinol, these values were also similar in alcoholic patients with or
      without skeletal myopathy. In the univariate analysis, we identified the total
      lifetime dose of ethanol (p < 0.003), the muscle arm area (p < 0.05), and serum
      levels of prealbumin (p < 0.03) and retinol-binding protein (p < 0.05) as factors
      influencing the development of alcoholic myopathy. However, in multivariate
      analysis, the total lifetime dose of ethanol was the only independent factor in
      relation to alcoholic myopathy (p < 0.003). Serum and muscle levels of the
      antioxidants alpha-tocopherol, ascorbic acid, and retinol do not influence the
      presence of skeletal myopathy in chronic alcoholic patients.

PMID- 9581650
TI  - Effect of pentylenetetrazole on ethanol intake, ethanol kinetics, and social
      behavior in male Wistar rats.
AB  - Stress and anxiety are often implicated in excessive alcohol use. The nature of
      this interaction, however, is not understood. The aim of this study was to
      examine the effect of the anxiogenic agent, pentylenetetrazole (PTZ), on the
      acquisition and maintenance of ethanol drinking behavior in male Wistar rats. In
      rats maintained on a limited access procedure, with a choice between a 12% w/v
      ethanol (ETOH) solution and water available for 30 min each day, acute PTZ
      administration (1.5 to 15.0 mg/kg) did not modify ETOH intake. Chronic PTZ
      administration elicited a significant suppression in ETOH intake; however, this
      effect developed gradually over time. During the acquisition phase, chronic PTZ
      treatment also suppressed ETOH consumption. Chronic, but not acute, treatment
      with PTZ seemed to enhance water consumption. To assess whether the effect of PTZ
      on ETOH intake was due to either alterations in ETOH kinetics or behavior, blood
      ETOH levels and social interaction behaviour were examined. PTZ (15.0 mg/kg)
      produced a significant suppression in social interaction behavior, although
      tolerance developed to this effect on chronic PTZ administration. Both acute and
      chronic PTZ treatment (15 mg/kg) resulted in lower blood ETOH levels achieved
      after administration of 1.0 g/kg po of ETOH. Because the anxiogenic effect of PTZ
      was not maintained on repeated administration, yet the suppression of ETOH intake
      was only observed after chronic treatment, this suggests a dissociation between
      the processes regulating these behaviors.

PMID- 9581651
TI  - Effect of alcohol on exercise-induced changes in serum glucose and serum free
      fatty acids.
AB  - The effect of alcohol on exercise-induced changes in serum glucose, serum free
      fatty acids, and serum insulin was studied in healthy male volunteers by
      performing an exhaustive ergometer exercise: (1) followed by alcohol intoxication
      (induced by 1.5 g of alcohol/kg of body weight); (2) during alcohol intoxication
      (induced by 0.8 g of alcohol/kg of body weight); and (3) during hangover (13 hr
      after a dose of 1.5 g of alcohol/kg of body weight). Acute alcohol intake
      immediately before exercise inhibited the exercise-induced increase in mean serum
      glucose concentration and caused a mild decrease in serum glucose levels during
      recovery from exercise. Exercise during hangover also resulted in decreased
      glucose levels during recovery from exercise. Alcohol administration immediately
      before or after exercise inhibited the postexercise increase in mean serum free
      fatty acids concentration. This was not seen during hangover, when blood alcohol
      concentration had already reached 0. In conclusion, alcohol interferes with the
      metabolism of carbohydrates during and after anaerobic exercise by decreasing the
      availability of circulating glucose. Furthermore, during recovery from exercise,
      alcohol decreases the supply of free fatty acids for the body.

PMID- 9581652
TI  - Involvement of kappa-opioids in the mouse cerebellar adenosinergic modulation of
      ethanol-induced motor incoordination.
AB  - Using rotorod performance as the test response, possible modulation and co
      modulation of ethanol-induced motor incoordination by the cerebellar kappa-opioid
      and adenosine A1 receptors was studied. A dose-related accentuation of ethanol
      induced motor incoordination was observed after direct cerebellar microinfusion
      of three kappa-opioid receptor agonists: U-50488, U-62066, and bremazocine. On
      the contrary, significant and dose-related attenuation of ethanol's motor
      impairment was produced by intracerebellar nor-binaltorphimine, a kappa-opioid
      receptor antagonist. Furthermore, the accentuation by kappa-agonists was
      virtually abolished by kappa-antagonist nor-binaltorphimine. Therefore, the
      accentuation and attenuation by kappa-opioid receptor agonists/antagonist,
      respectively, was through specific kappa-opioid receptors. Pretreatment with the
      intracerebellar adenosine A1-selective agonist, N6-cyclohexyladenosine, further
      enhanced the ethanol-induced motor incoordination and its accentuation by
      intracerebellar kappa-opioid receptor agonists. Ethanol-induced motor
      incoordination was markedly attenuated by intracerebellar pertussis toxin (PTX)
      pretreatment, suggesting an involvement of PTX-sensitive G protein in the
      expression of motor incoordinating effect of ethanol. Additionally, the
      intracerebellar PTX also markedly attenuated the accentuation by kappa-opioid
      agonists of ethanol-induced motor impairment, suggesting participation of PTX
      sensitive GTP-binding G protein (Gi, Go) in the kappa-opioid modulation of
      ethanol's motor impairment. It also confirms that kappa-opioid receptors are
      linked to PTX-sensitive G protein. The functional similarity between kappa-opioid
      and adenosine A1 receptors in increasing ethanol's motor incoordination, together
      with their anatomical co-localization primarily on the axons and axonal terminals
      of the cerebellar granule cells, suggests a possible common catalytic unit of
      adenylate cyclase as the basis of modulation of ethanol-induced motor
      incoordination by both receptor mechanisms.

PMID- 9581653
TI  - P-450-dependent metabolism of lauric acid in alcoholic liver disease: comparison
      between rat liver and kidney microsomes.
AB  - Monooxygenase enzymatic activities were measured in liver and kidney microsomes
      of control and ethanol-treated rats. Animals were administered alcohol by using a
      model for alcoholic liver injury. Several in vitro approaches were used to
      compare the laurate metabolism in liver and kidney microsomes: correlation
      studies between specific P-450 catalytic activities, immunoblot analysis, and
      chemical and immunoinhibitions. Ethanol treatment increased the liver and renal
      hydroxylations of chlorzoxazone and 4-nitrophenol. Moreover, lauric acid (omega
      1)-hydroxylation was found to be significantly increased (-6-fold) after ethanol
      treatment in liver, but not in kidney microsomes. The laurate omega-1/omega ratio
      increased from 1.52 +/- 0.49 to 4.11 +/- 1.01 in liver microsomes of control and
      ethanol-treated rats, and from 0.29 +/- 0.06 to 0.44 +/- 0.07 in kidney
      microsomes. Immunoblot analysis using polyclonal anti-cytochrome P-450 (CYP) 2E1
      or CYP4A antibodies showed an increase of CYP2E1 and CYP4A contents in both
      organs, but the increase was higher in liver than in kidney microsomes. Chemical
      inhibitions using CYP2E1 competitive inhibitors (such as chlorzoxazone and
      ethanol) led to a nonsignificant inhibition of the renal (omega-1)-hydroxylation
      of lauric acid. In contrast, 17-octadecynoic acid (a mechanism-based inhibitor of
      omega-hydroxylase) was able to inhibit both omega- and (omega-1)-hydroxylations
      of lauric acid in kidney microsomes. Immunoinhibitions specific to CYP2E1
      significantly decreased the (omega-1)-hydroxylation of lauric acid in liver, but
      not in kidney microsomes, whereas the polyclonal anti-CYP4A1 antibody inhibited
      omega- and (omega-1)-hydroxylations of lauric acid in kidney microsomes. All of
      these results show that lauric acid hydroxylations in liver and kidney respond in
      different manners to ethanol treatment. Lauric acid (omega-1)-hydroxylation, a
      highly specific probe for CYP2E1 in rat and human liver microsomes, is mediated
      by a CYP4A isoform in rat kidney microsomes.

PMID- 9581654
TI  - Influence of chronic alcohol intake on intestinal taurine and antipyrine
      transport in pregnant rats.
AB  - Taurine is a nonessential amino acid that plays a critical role in development.
      However, biosynthetic capacity is almost negligible in the fetus and must be
      supplied by the mother. Therefore, when maternal taurine status is depressed
      during gestation, fetal tissue taurine concentrations can also be compromised. In
      the present study, the effect of chronic alcohol intake on the intestinal
      transport of taurine during pregnancy has been investigated by an in vitro
      technique that allows measurement of the unidirectional influx of the amino acid
      across the intact rat mid jejunum. The influence of alcohol intake on the passive
      component of the intestinal transport was also investigated with antipyrine, a
      model compound for passive diffusion. For chronic alcohol treatment, the rats
      were fed a liquid diet containing ethanol (36% of calories) or an isocaloric diet
      (pair-fed control) for 5 weeks before and during pregnancy. The animals were
      sacrificed at 21 days of gestation. Results from the kinetic analysis revealed
      that chronic ethanol treatment significantly decreases the maximum transport (Jm)
      of taurine, without modifying the Michaelis-Menten constant (Km), but enhances
      its diffusion component (ka) compared with that of controls. At the same time,
      this treatment significantly increased the passive diffusion of antipyrine. These
      results indicate that although chronic ethanol inhibits the active transport of
      taurine, passive diffusion is significantly increased. However, because of the
      predominant passive component in the intestinal absorption of taurine, an overall
      enhancement in the absorption of this amino acid is observed in alcohol-fed rats.
      The biological and practical implications of our results are discussed.

PMID- 9581655
TI  - Ethanol reward and aversion in mice bred for sensitivity to ethanol withdrawal.
AB  - The present study examined mice selectively bred for sensitivity to ethanol
      withdrawal for differences in the conditioned place preference (CPP) and
      conditioned taste aversion (CTA) paradigms. Withdrawal Seizure-Prone (WSP) and
      Withdrawal Seizure-Resistant (WSR) mice and High Alcohol Withdrawal (HAW) and Low
      Alcohol Withdrawal (LAW) mice were selectively bred for differences in chronic
      and acute ethanol withdrawal, respectively. For the CPP experiment, male HAW and
      LAW (generation 5) mice received four pairings of ethanol (2 g/kg), with a
      distinctive floor stimulus. On intervening days, mice received saline paired with
      an alternate floor type. During the preference test, all mice received an
      injection of saline before 60-min access to both floor types. HAW mice showed
      conditioned preference for the ethanol-paired floor, whereas LAW mice did not.
      For the CTA experiments, male HAW, LAW, WSP, and WSR mice were adapted to a 2
      hr/day water restriction regimen and subsequently received ethanol injections (0,
      2, 2.5, or 4 g/kg, i.p.) immediately after 1-hr access to a NaCl-flavored
      solution. Dose-dependent reductions in NaCl intake reflected the development of
      CTA in both HAW/LAW and WSP/WSR lines. However, a smaller magnitude of CTA was
      observed in WSP mice relative to WSR mice after the first ethanol-NaCl pairing.
      WSP/WSR mice showed similar reductions of NaCl intake on subsequent conditioning
      trials. Overall, these data suggest that HAW mice selectively bred for high
      sensitivity to acute ethanol withdrawal are more sensitive to the rewarding
      effects of ethanol in the CPP paradigm. This outcome is consistent with a
      previous study showing greater CPP in WSP mice relative to WSR mice. In the CTA
      paradigm, sensitivity to ethanol withdrawal in the HAW/ LAW selected lines does
      not appear to be genetically correlated with sensitivity to the aversive
      properties of ethanol. However, the difference in acquisition of CTA in WSP/WSR
      lines suggest that some genes determining ethanol withdrawal severity may also
      influence initial sensitivity to ethanol's aversive effects.

PMID- 9581656
TI  - Chronic alcohol intoxication attenuates human immunodeficiency virus-1
      glycoprotein 120-induced superoxide anion release by isolated Kupffer cells.
AB  - This work tests the hypothesis that chronic alcohol intoxication suppresses the
      microbicidal activity of Kupffer cells by modulating the expression of cell
      surface receptors associated with respiratory burst and the release of potent
      microbicidal agents [i.e., reactive oxygen species (ROS)]. Because alcohol is
      also a potential risk factor in human immunodeficiency virus-1 (HIV-1) infection,
      this study examines the effect of HIV-1 glycoprotein 120 (gp120)-induced ROS
      release by isolated Kupffer cells. After 16 weeks of ethanol feeding, Kupffer
      cells from male Sprague-Dawley rats were isolated and assayed for HIV-1 gp120
      induced superoxide release. Fluorescein isothiocyanate (FITC)-HIV-1 gp120
      binding, NADPH oxidase, and protein kinase C activity in Kupffer cells were
      measured. Results show that HIV-1 gp120 induced the release of superoxide anion
      in a dose-dependent manner in normal rats. Mannosylated-bovine serum albumin
      inhibited FITC-HIV-1 gp120-mediated superoxide release in normal Kupffer cells by
      85%. Moreover, 83 +/- 6% of Kupffer cells were FITC-HIV 1 gp120-positive, whereas
      <30% were CD4-positive. In alcohol-fed rats, HIV-1 gp120-induced ROS release was
      reduced by 70% and FITC-HIV-1 gp120 binding (in terms of fluorescence intensity
      per 10[6] Kupffer cells) by 44% in Kupffer cells, without any change in percent
      positive cells for this ligand. Concomitantly, HIV-1 gp120-induced translocation
      of NADPH oxidase to the plasma membranes of Kupffer cells in alcohol-fed rats was
      suppressed by 60%. In contrast, alcohol consumption significantly increased total
      protein kinase C activity and phorbol ester-induced superoxide release by Kupffer
      cells. These studies demonstrate that Kupffer cells are likely targets of HIV-1
      whose binding sites on macrophages could also include mannose-specific receptors.
      These observations further suggest that suppression of HIV-1 gp120-mediated ROS
      production in chronic alcoholics is due to altered cell surface receptor
      expression for gp120, and defective postreceptor signaling mechanisms, which in
      turn could lead to attenuated microbicidal activity of hepatic macrophages.

PMID- 9581657
TI  - Induction of Fos-like proteins and ultrasonic vocalizations during ethanol
      withdrawal: further evidence for withdrawal-induced anxiety.
AB  - The ethanol withdrawal syndrome includes anxiety as a prominent symptom. Because
      the extent that specific regions of brain are critical to the generation of this
      emotional state is unknown, Fos-like immunoreactivity (Fos-LI) was used to
      associate specific regions of the rat brain with the anxiety component of the
      ethanol withdrawal syndrome exacerbated by an air puff challenge in rats. Chronic
      ethanol liquid diet was administered intragastrically for 4 days or by having the
      rats consume the diet for 14 days. During withdrawal from either treatment
      protocol, Fos-LI was induced most prominently in forebrain areas, although the
      midbrain and hindbrain were also represented. Included in these Fos-LI positive
      regions were many cortical regions, septum, accumbens, claustrum, amygdala,
      paraventricular nucleus of the thalamus and hypothalamus, hippocampus, locus
      coeruleus, and central gray. Fos-LI expression differed mostly in intensity
      between the two treatment and withdrawal protocols, with the gastric protocol
      producing the greatest Fos-LI induction in most brain regions. The threshold for
      air puff-induced ultrasonic vocalizations was decreased, and the number of
      vocalizations was increased and the period of vocalization was extended. These
      behavioral data indicate that aversively motivated responding in rats during
      ethanol withdrawal can be readily quantified with the ultrasonic vocalizations
      test without precipitating convulsive activity. Furthermore, a comparison of the
      effects of the air puff challenge versus withdrawal on Fos-LI indicated that the
      behavioral state induced in these two situations share functional neuroanatomical
      features. Some regions--such as the accumbens core, medial septum, subregions of
      the amygdala, hippocampus, substantia nigra, and cerebellum--exhibited little Fos
      LI during withdrawal and also did not exhibit strong increases after the addition
      of the air puff challenge. However, other regions-such as the cerebral cortex
      (medial prefrontal, frontal, cingulate and ventrolateral orbital, claustrum, and
      tenia tecta), hypothalamus, and locus ceoruleus- exhibited Fos-LI at levels
      higher than that seen after either the ethanol withdrawal or puff challenge
      alone. These overlapping patterns of Fos-LI in specific regions of the brain,
      activated by both ethanol withdrawal and an anxiety provoking behavioral
      challenge, suggest that specific neuroanatomical sites in brain are associated
      with the symptom of anxiety observed during the "ethanol withdrawal syndrome."

PMID- 9581658
TI  - Hepatic stellate cells and liver retinoid content in alcoholic liver disease in
      humans.
AB  - Body retinoids are stored in the lipid droplets of hepatic stellate (Ito) cells.
      In chronic liver disease, the stellate cells differentiate into myofibroblast
      like cells, a process whereby they lose their retinoid-containing lipid droplets.
      We studied the relation between liver retinoid content, the number of lipid
      droplets per stellate cell, and the number of stellate cells per mm2 in human
      alcoholic liver disease. Semithin sections of liver biopsies from normal subjects
      and patients with early (steatosis, inflammation, and mild fibrosis) and late
      (cirrhosis and cirrhosis with acute alcoholic hepatitis) alcoholic liver disease
      were morphometrically evaluated. Liver retinoid content was determined by HPLC.
      In normal patients, liver retinoid content was 901 +/- 213 IU/g of liver (mean +/
      SEM). There was a decrease in liver retinoid content in early alcoholic liver
      disease (409 +/- 50 IU/g) and a further reduction in cirrhosis (153 +/- 50 IU/g).
      In patients with acute alcoholic hepatitis, retinoid content was strikingly low
      (5.2 +/- 1.8 IU/g). There was a progressive decrease in the number of stellate
      cells per mm2 associated with progressive liver damage. We found a fair
      correlation between the number of stellate cells per mm2 and liver retinoid
      content in all patient groups (overall correlation: 0.71). In normal subjects,
      the mean number of lipid droplets per stellate cell was 7.4 +/- 0.7. In patients
      with early alcoholic liver disease and in patients with alcoholic cirrhosis, this
      value was increased to 13.6 +/- 0.8 and 10.4 +/- 2.0, respectively. In patients
      with acute alcoholic hepatitis, only a few lipid droplets were present (4.2 +/-
      0.5). There was a good correlation between liver retinoid content and mean number
      of lipid droplets in normal patients (r = 0.58). In alcoholic cirrhosis, however,
      correlation was poor (r = 0.34). In early alcoholic liver disease, the
      correlation was absent (r = 0.004). In conclusion, the major finding of our study
      is that the correlation between the mean number of lipid droplets per stellate
      cell and liver retinoid content varies according to the hepatic pathology
      considered. Marked lipid droplet accumulation occurs in stellate cells in early
      alcoholic liver disease and, to a lesser extent, in alcoholic cirrhosis, but
      there is no correlation between the mean number of lipid droplets per stellate
      cell and liver retinoid content. Therefore, not retinoids but probably lipids are
      responsible for the accumulation of lipid droplets. We also find that there is a
      fair correlation between the number of stellate cells per mm2 and liver retinoid
      content in all patient groups. Finally, we confirm the decrease in hepatic
      retinoid content that occurs in alcoholic liver disease in humans, even at the
      early stages of the disease.

PMID- 9581659
TI  - Inducibility of cytochromes P-4502E1 and P-4501A1 in the rat pancreas.
AB  - Cytochrome P-450 (CYP) isoenzymes have been incriminated in the toxicity and
      carcinogenicity of various xenobiotics in different tissues, but prior
      measurements of their activity in pancreatic microsomes have been disappointing.
      We now applied new isolation methods and a highly sensitive procedure to assay
      for the metabolism of p-nitrophenol and 7-ethoxyresorufin, specific substrates
      for CYP2E1 (2E1) and CYP1A1 (1A1), respectively. 2E1 and 1A1 content was
      estimated with high-resolution chemiluminescent Western blots using recombinant
      2E1 and 1A1 as standards. We found that p-nitrophenol hydroxylase activity was
      5.07 +/- 0.66 and 1.50 +/- 0.26 pmol/ min/mg of protein in pancreatic microsomes
      of ethanol-fed and control rats, respectively. Chronic ethanol treatment
      increased 2E1 content in pancreatic microsomes 3.6-fold. Activity and content of
      2E1 were also assessed in hepatic microsomes: specific activity (expressed per
      2E1 content) was similar in pancreatic and hepatic microsomes. There was also an
      inductive effect of 3-methylcholanthrene (MC) on 1A1 in pancreatic microsomes.
      Pancreatic microsomal 7-ethoxyresorufin-O-dealkylation activity in MC-treated
      rats was 19.6 +/- 1.7 pmol/min/mg of protein, 61-fold higher than in controls. MC
      treatment increased the 1A1 content in pancreatic microsomes 42-fold. These
      results demonstrate that, in pancreatic microsomes, ethanol and MC exert striking
      inductive effects on 2E1 and 1A1 activities, which could play a role in the
      pathogenesis of pancreatitis and/or pancreatic cancer.

PMID- 9581660
TI  - A family-based analysis of the association of the dopamine D2 receptor (DRD2)
      with alcoholism.
AB  - The possible association of the DRD2 locus, and in particular the Taql-A1 allele,
      with alcoholism remains controversial, in part because of differences in allele
      frequencies among populations. To avoid problems associated with differences in
      allele frequencies in different populations, we tested whether the DRD2 locus is
      associated with alcohol dependence in a large family-based sample. Neither the
      transmission/disequilibrium test nor the Affected Family-Based Controls test
      provide any evidence of linkage or association between the DRD2 locus and alcohol
      dependence.

PMID- 9581661
TI  - A model to examine the validity of the 6-month abstinence criterion for liver
      transplantation.
AB  - Six months of abstinence from alcohol is a commonly used criterion for liver
      transplantation eligibility for patients with alcoholic cirrhosis. There is
      limited evidence to document the validity of this criterion with regard to risk
      of alcoholism relapse. Ninety-one patients with alcoholic cirrhosis were
      interviewed for relapse risk using the High Risk Alcoholism Relapse (HRAR) Scale.
      The HRAR model can be used to predict relapse risk independent of duration of
      sobriety and therefore can be used to examine the validity of the 6 months of
      abstinence criteria in this clinical population. The two methods demonstrated
      poor to fair agreement. Agreement was highest with a cutoff allowing a 5% 6-month
      relapse risk when 79% agreement (c = 0.56) was demonstrated between the two
      methods. Using the 6-month abstinence criterion alone disallows a significant
      number of candidates who have a low relapse risk based on their HRAR score. The
      validity of the 6-month abstinence criterion is supported somewhat by comparison
      with the HRAR model. However, use of the 6-month abstinence criterion alone
      forces a significant number of patients with a low relapse risk by HRAR to wait
      for transplant listing. A relapse risk model based on an estimate of alcoholism
      severity in addition to duration of sobriety may more accurately select patients
      who are most likely to benefit from liver transplantation.

PMID- 9581662
TI  - Relationship of binge drinking to alcohol dependence, other psychiatric
      disorders, and behavioral problems in an American Indian tribe.
AB  - The hypothesis that binge drinking is a benign behavior not associated with
      alcohol dependence, other psychiatric disorders, or problem areas, in American
      Indians, was tested in a sample of 582 adult Southwestern American Indian males
      and females in large multigenerational pedigrees. All information was obtained
      from semistructured psychiatric interviews that were independently blind-rated
      for DSM-III-R diagnoses. Three main outcome measures were used: the relationship
      between binge drinking and (1) alcohol dependence and other psychiatric
      disorders, (2) substance abuse treatment, and (3) four behavioral problem
      categories-violence/lawlessness, physical, social, and work. Binge drinking and
      alcohol dependence were strongly associated. Most binge drinkers were diagnosed
      as alcohol dependent. However, when controlling for alcohol dependence and other
      covariates, binge drinking was independently associated with an increase in odds
      for positive diagnoses for multiple psychiatric disorders, and for social, work,
      physical, and violence/lawlessness behavioral problems. In sum, binge drinking
      was found to be a common and severe problem with deleterious consequences in
      multiple domains of functioning. Assessment instruments should be designed to
      elicit information on binge patterns of drinking and strategies devised to
      provide appropriate treatment.

PMID- 9581663
TI  - Clinical characteristics and disease course of alcoholics with inactive aldehyde
      dehydrogenase-2.
AB  - Inactive aldehyde dehydrogenase-2 (ALDH2) is known as a genetic negative risk
      factor for the development of alcoholism. In alcoholics with inactive ALDH2,
      unidentified factors that overcome the adverse reactions of high blood
      acetaldehyde concentration after drinking may increase such persons'
      susceptibility to alcoholism. Comparison of clinical characteristics, including
      sociofamilial backgrounds and psychopathologies, failed to show significant
      differences between alcoholics with inactive ALDH2 (inactive group) and those
      with active ALDH2 (active group). Examination of the temporal profile of disease
      development showed that the inactive group experienced each stage or event in the
      history of drinking and alcoholism 1 to 5 years later in life than the active
      group; however, not all comparisons reached statistically significant levels.
      Although preliminary, these results suggest that an inactive ALDH2-mediated delay
      in the occurrence of alcohol-related problems seems to contribute to the
      suppression of alcoholism development.

PMID- 9581664
TI  - Comparison of social abilities of children with fetal alcohol syndrome to those
      of children with similar IQ scores and normal controls.
AB  - Children diagnosed with fetal alcohol syndrome (FAS) were assessed with items
      from the social skills domain of the Vineland Adaptive Behavior Scales (VABS) via
      interviews with their caregivers. Their scores were compared with scores from
      children in two control groups. The control groups included children matched for
      IQ to the FAS group (specifically on verbal IQ, henceforth, the VIQ group) and
      children with IQ scores in the average to above-average range (normal control
      group). Forty-five children (age range, 5 years 7 months to 12 years 11 months)
      were assessed (n/group = 15). All groups differed with regard to social ability,
      as measured by the VABS (NC > VIQ > FAS), even when the effects of socioeconomic
      status were held constant. The three subdomains of the VABS social scale
      (interpersonal relationship skills, use of play and leisure time, and coping
      skills) were assessed, and results showed that the children with FAS were most
      impaired on the subdomain that assessed interpersonal relationship skills. An
      additional measure was constructed by obtaining an age-equivalent score for the
      VABS social scale and calculating a difference score by subtracting the child's
      chronological age from his/her age-equivalent score. There was a significant
      correlation between chronological age and difference scores for children in the
      FAS group but not for children in the two control groups. Specifically, in older
      children with FAS, there was an increased discrepancy between their ages and
      their age-equivalent scores, a discrepancy that was not present in children in
      the control groups. These results suggest that social deficits in children with
      FAS are beyond what can be explained by low IQ scores and indicate that there may
      be arrested, and not simply delayed, development of social abilities in children
      with FAS.

PMID- 9581665
TI  - Trends in alcohol-related problems among whites, blacks, and Hispanics: 1984
      1995.
AB  - The objective of this study was to report trends in alcohol problems among
      whites, blacks, and Hispanics between 1984 and 1995. Data were obtained from two
      nationwide probability samples of U.S. households, the first conducted in 1984
      and the second in 1995. The 1984 sample consisted of 1777 whites, 1947 blacks,
      and 1453 Hispanics. The 1995 sample included 1636 whites, 1582 blacks, and 1585
      Hispanics. On both occasions, interviews (average length, 1 hr) were conducted in
      respondents' homes by trained interviewers. The results indicate that between
      1984 and 1995, alcohol problems were stable among white and black men and
      increased among Hispanic men. The rates of three or more alcohol problems for men
      of each ethnic group for 1984 and 1995 were: 12% and 11% for white men, 16% and
      13% for black men, and 9% and 16% for Hispanic men, respectively. Problem
      prevalence was stable and relatively low among women in all three ethnic groups.
      Overall, the prevalence of alcohol problems continues to be high among men in the
      United States. Even though recent research has shown that rates of frequent heavy
      drinking among white men have declined, we found no corresponding decrease in
      problem prevalence. Rates of frequent heavy drinking and alcohol-related problems
      between 1984 and 1995 have remained especially high among black and Hispanic men,
      suggesting that men of these two ethnic groups should be specifically targeted
      for renewed prevention efforts.

PMID- 9581667
TI  - Voices of the afflicted.
AB  - Over the past 10 years, I have been privileged to conduct educational forums for
      audiences containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from those afflicted can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcohol
      dependence.

PMID- 9581666
TI  - Pretreatment with isradipine, a calcium-channel blocker, does not attenuate the
      acute behavioral effects of ethanol in humans.
AB  - The acute subject-rated, performance-impairing, and physiological effects of
      ethanol (0, 0.5, and 1 g/kg) were examined after pretreatment with isradipine (0,
      5, and 10 mg) in nine healthy volunteers. Volunteers received 1 of the 9 ethanol
      isradipine combinations during each of nine experimental sessions. Ethanol alone
      produced prototypical subject-rated drug effects (e.g., increased ratings of
      "Drunk," "Good effects," and "Like drug") and impaired performance. Isradipine
      alone also produced significant subject-rated drug effects (e.g., increased
      ratings of "Drug effect," "Bad effects," "High," and "Stimulated"), but did not
      impair performance. Isradipine pretreatment generally did not significantly alter
      the subject-rated or performance-impairing effects of ethanol. Isradipine alone,
      but not ethanol alone, significantly decreased systolic and diastolic blood
      pressure. The ethanol-isradipine combinations generally produced significantly
      greater decreases in blood pressure than were observed with isradipine alone.
      Breath-alcohol levels were significantly lower after isradipine pretreatment,
      which suggests isradipine altered the bioavailability of ethanol. The present
      findings extend previous studies with humans that examined the behavioral effects
      of ethanol after pretreatment with other calcium-channel blockers, including
      nifedipine, nimodipine, and verapamil. Whereas the available studies suggest that
      calcium-channel blockers would not be useful pharmacological adjuncts in the
      management of ethanol abuse, more research is needed. Future studies should use
      self-administration and drug discrimination procedures adapted for use with
      humans to determine if calcium-channel blockers can attenuate any of the
      behavioral effects of ethanol.

PMID- 9581668
TI  - Pathogenesis of alcoholic pancreatitis--a peak into a black box.

PMID- 9581669
TI  - The incidental focal liver lesion: photon, proton, or needle?

PMID- 9581670
TI  - Increased renal expression of nitric oxide synthase type III in cirrhotic rats
      with ascites.
AB  - This article assesses the circulating levels of L-arginine, the renal response to
      L-arginine infusion, and the renal expression of inducible and constitutive
      nitric oxide synthase (NOS II and NOS III, respectively) in cirrhotic rats with
      ascites. Systemic and renal hemodynamics and renal function were measured in
      basal conditions and following two doses of L-arginine (5 and 10 mg x kg(-1) x
      min for 40 minutes). Renal NOS II and III messenger RNA (mRNA) expression was
      evaluated in basal conditions by polymerase chain reaction and Northern blot,
      respectively. Renal NOS II and III protein expression was assessed by Western
      blot and immunohistochemistry. Plasma concentration of L-arginine was
      significantly lower in cirrhotic rats than in control rats (48+/-11 vs. 86+/-9
      micromol/L, P < .025). In both groups L-arginine infusion had no effect on
      systemic hemodynamics, but markedly increased renal perfusion. This effect was
      significantly more intense in cirrhotic rats. A very weak signal of similar
      intensity was found for NOS II mRNA in both groups of animals. However, no NOS II
      protein expression was detected. In contrast, higher NOS III mRNA abundance and
      protein expression, which was mainly located in the endothelial lining of the
      renal arterioles, were found in the kidney of cirrhotic animals. These results
      indicated increased renal expression of NOS III mRNA and protein, deficient
      circulating levels of L-arginine, and increased renal hemodynamic response to
      this amino acid in cirrhotic rats with ascites. Our results suggest that L
      arginine supplementation at doses not affecting arterial pressure could have
      beneficial effects on renal perfusion in cirrhosis.

PMID- 9581671
TI  - Decreased muscle strength in patients with alcoholic liver cirrhosis in relation
      to nutritional status, alcohol abstinence, liver function, and neuropathy.
AB  - To study motor function quantitatively in alcoholic liver cirrhosis muscle
      strength, liver function, peripheral nerve function, and nutrition were assessed
      in 24 patients. Isokinetic strength of flexion and extension at elbow, wrist,
      hip, knee, and ankle and of shoulder abduction and adduction was evaluated and
      compared with findings in 24 matched healthy subjects. Degree of liver disease
      was assessed with the Child-Pugh score and the galactose elimination capacity
      (GEC). Nutritional status was evaluated with an estimation of lean body mass
      (LBM) from 24-hour urinary creatinine excretions. Peripheral nerve function was
      evaluated with neurological symptom and disability scores, nerve conduction
      studies, and quantitative sensory tests summed to obtain a neuropathy rank-sum
      score (NRSS) for each patient. Combined muscle strength at hip, knee, ankle,
      shoulder, elbow, and wrist were weakened with 34% (P < .005), 35% (P < .001), 35%
      (P < .01), 34% (P < .01), 29% (P < .01), and 29% (P < .02), respectively. The
      median Child-Pugh score was 7 (range, 5-12), and the median duration of alcohol
      abstinence was 90 days (range, 5-960 days). After multiple linear regression
      analysis including LBM, Child-Pugh score, GEC, duration of alcohol abstinence,
      and NRSS, only LBM was correlated to the strength at the knee (r=.79; P < .0001)
      and at the ankle (r=.63; P < .01). It is concluded that muscle strength is
      weakened substantially in alcoholic patients with liver cirrhosis and that
      weakness is related to the severity of malnutrition but not to the severity of
      liver disease, duration of alcohol abstinence, or neuropathy.

PMID- 9581672
TI  - Bacterial infection is independently associated with failure to control bleeding
      in cirrhotic patients with gastrointestinal hemorrhage.
AB  - Bacterial infection is frequently diagnosed in cirrhotic patients with variceal
      hemorrhage. The aim of this study was to assess the incidence of failure to
      control bleeding in cirrhotic patients during the first 5 days after the episode
      of variceal bleeding in relation to the diagnosis of bacterial infection and use
      of antibiotics. One hundred seventy-seven consecutive admissions for
      gastrointestinal bleeding in 151 patients were evaluated prospectively. From
      them, 163 admissions for variceal bleeding in 137 patients were included in the
      main analysis. Bleeding was managed in a standardized protocol using octreotide
      or terlipressin with sclerotherapy or band ligation for active bleeding at
      endoscopy. The end points were defined as in Baveno guidelines related to
      transfusion requirement or fresh hematemesis after 6 hours from time zero. The
      standardized screening protocol for bacterial infection consisted of chest
      radiograph and blood, urine, and ascitic fluid cultures. Active bleeding was
      reported at endoscopy in 86 admissions (53%). Failure to control bleeding
      occurred in 76 patient admissions (47%). Empirical antibiotic treatment was used
      in 113 admissions (69%), whereas in 81% of them (91 admissions, 56%) 102
      bacterial infections were documented. Multivariate analysis showed that proven
      bacterial infection (P < .0001) or antibiotic use (P < .003) as well as active
      bleeding at endoscopy (P < .001) and Child-Pugh score (P < .02) were independent
      prognostic factors of failure to control bleeding. The results remained unchanged
      when all patient admissions with gastrointestinal bleeding of any source were
      included in the multivariate analysis. Bacterial infection is associated with
      failure to control variceal bleeding and needs to be evaluated in the planning
      and analysis of clinical trials.

PMID- 9581673
TI  - Factors associated with serum alanine transaminase activity in healthy subjects:
      consequences for the definition of normal values, for selection of blood donors,
      and for patients with chronic hepatitis C. MULTIVIRC Group.
AB  - In clinical research, the definition of the upper limit of normal (ULN) alanine
      transaminase (ALT) is never detailed. However, such a definition can vary and may
      have practical consequences. Our aim was to assess factors associated with serum
      ALT activity in apparently healthy subjects and then to apply seven different
      definitions of ULN in three different populations so as to assess the prevalence
      of subjects with normal ALT among blood donors and among hepatitis C patients
      before (normal ALT hepatitis C patients) and after treatment (interferon [IFN]
      responders). ALT measurements were performed in the same laboratory using the
      same technique; 1,033 donors were prospectively investigated, 186 patients with
      hepatitis C never treated and 40 patients treated with 3 MU three times per week
      of IFN-alpha for at least 6 months. The seven definitions (D) of ULN were: D1:
      95th percentile of ALT; D2: 95th percentile after separating males and females;
      D3: males and females separately, ULN=10 (mean of log10 ALT + 1.96 SD); D4:
      ULN=45 IU/L given by the manufacturer; D5: mean + 1 SD after exclusion of the 5%
      extreme values; D6: 95th percentile after separating subjects with body mass
      index (BMI) under or equal to the median (23); and D7: 95th percentile after
      separating subjects according to BMI and sex. BMI and male sex were independently
      associated (P < .0001; logistic regression) with ALT, without an association with
      alcohol. The range of ULN varied from 26 IU/L in females (D5) to 66 IU/L in males
      with BMI >23 (D7). Depending on the definition, the prevalence of blood donors
      with normal ALT varied from 82% to 96%, i.e., a range of 14%; that of hepatitis C
      patients with normal ALT varied from 16% to 27%, i.e., a range of 11%; the
      prevalence of IFN responders varied from 25% to 42%, i.e., a range of 17%.
      Definitions of normal ALT values should be adjusted for sex and BMI to reduce
      artificial heterogeneity in blood donor selection and in hepatitis C clinical
      studies.

PMID- 9581674
TI  - Cost-effectiveness of ultrasound-guided liver biopsy.
AB  - The risk of a major complication from "blind" percutaneous liver biopsy is
      reported to be in the range of 0.24% to 3.8%. In a recent randomized trial,
      patients whose liver biopsies were performed with ultrasonography had a
      significant reduction in complications requiring hospitalization compared with
      patients without ultrasound-guided biopsies (0.5% vs. 2.2%, P < .05). Despite
      this, routine use of ultrasonography for liver biopsies has not been implemented
      because of controversies with respect to cost-effectiveness. The aim of our study
      was to analyze the relative cost-effectiveness of performing ultrasound-guided
      liver biopsies using decision analysis. A decision tree was constructed to
      compare a strategy of liver biopsy using ultrasonography with a strategy without
      ultrasonography. The major outcomes included were minor complications such as
      pain requiring analgesics and major complications, which require hospitalization.
      Costs included were direct medical costs from the payer's perspective. In our
      baseline model, the cost from complications per patient with and without
      ultrasonography was $62 and $129, respectively. The marginal effectiveness
      expressed as the number of major complications avoided was 1.2/100 liver
      biopsies. The incremental cost to avoid one major complication was $2,731. The
      model was most sensitive to the frequency of major complications and the
      additional cost of ultrasonography. Our decision analysis model suggests that
      ultrasound-guided liver biopsy is cost-effective. Future studies assessing the
      efficacy of image-guided liver biopsies should be conducted.

PMID- 9581675
TI  - Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in
      cirrhosis: relationship with the development of renal impairment and mortality.
AB  - Spontaneous bacterial peritonitis (SBP) is associated with an important
      production of inflammatory mediators. However, it is unknown whether there is a
      relationship between the abdominal production of these mediators and the
      development of renal impairment, one of the most important prognostic parameters
      in spontaneous bacterial peritonitis. We studied 52 cirrhotic patients at
      diagnosis and resolution of the infection, by measuring endotoxin, tumor necrosis
      factor (TNF), and interleukin-6 (IL-6) levels in plasma and ascitic fluid.
      Thirteen patients (25%) developed renal impairment. Patients developing renal
      impairment showed significantly higher plasma and ascitic fluid cytokine levels
      at diagnosis of infection than patients who did not (plasma TNF-alpha: 96.0+/
      38.7 vs. 39.1+/-3.6 pg/mL, P=.0209; ascitic fluid TNF-alpha: 474.5+/-118.1 vs.
      160.8+/-42.7 pg/mL, P=.0173; plasma IL-6: 6,635+/-2,897 vs. 458+/-109 pg/mL,
      P=.0004; ascitic fluid IL-6: 182,559+/-47,328 vs. 39,250+/-10,803 pg/mL,
      P=.0001). Independent predictors of development of renal impairment at diagnosis
      were: renal failure (blood urea nitrogen > 30 mg/dL or serum creatinine > 1.5
      mg/dL) (P < .001), IL-6 levels in ascitic fluid (P < .001), and mean arterial
      pressure (P < .05). Ten of the 13 (77%) patients who developed renal impairment
      died during hospitalization, but only 2 of the 39 (5%) patients who did not
      (P=.0001). In addition, renal failure at diagnosis of the infection was the only
      independent predictor of hospital mortality (P < .001). In conclusion, the
      inflammatory response to the infection may be an important mechanism of renal
      impairment and the associated mortality in SBP.

PMID- 9581676
TI  - Loss of butyrate-induced apoptosis in human hepatoma cell lines HCC-M and HCC-T
      having substantial Bcl-2 expression.
AB  - We have demonstrated that sodium butyrate induces differentiation in human
      hepatoma cells; however, recent studies have shown that this agent causes
      apoptosis in some types of cancer cells. In this study, we examined whether
      sodium butyrate causes apoptosis in the human hepatoma cell lines, HCC-M and HCC
      T. The growth of human hepatoma cells was dose-dependently reduced by sodium
      butyrate. Flow cytometric analysis showed cell-cycle arrest at the G1 phase in
      the sodium butyrate-treated cells. Apoptotic change was never found in treated
      cells at concentration levels of less than 5 mmol/L. Sodium butyrate decreased
      p53 expression and increased p21WAF-1 expression in HCC-T and HCC-M cells having
      the wild-type p53 gene. Western blot analysis showed that Bcl-2 was expressed in
      the HCC-T and HCC-M cells, and its expression was increased after exposure to
      sodium butyrate. Antisense oligodeoxynucleotide against bcl-2 easily caused
      apoptosis. These results indicate that sodium butyrate hardly induces apoptotic
      change in the human hepatoma cell lines, HCC-T and HCC-M, with the increase of
      Bcl-2 expression. Cell-cycle arrest in the G1 phase caused by sodium butyrate was
      suggested to be induced by the increase in p21WAF-1 expression, but this change
      did not link with the p53 increase.

PMID- 9581677
TI  - Inhibition of establishment and growth of mouse liver metastases after treatment
      with interferon gamma and beta-1,3-D-glucan.
AB  - The purpose of this study was to investigate the combined antitumor effect of
      aminated beta-1,3-D-glucan (AG) and interferon-gamma (IFN-gamma) in an
      experimental liver metastasis model. Liver metastases were established by
      inoculation of C-26 colon carcinoma cells into the superior mesenteric vein of
      syngeneic mice. Treatment of mice started 24 hours after inoculation of tumor
      cells by daily intravenous injections of either AG, IFN-gamma, or a combination
      of both for a duration of 6 days. The resultant liver metastases were then
      quantified after an additional period of 11 days. Combination of IFN-gamma and AG
      inhibited the growth of liver metastases almost entirely. IFN-gamma was also very
      efficient, while AG alone did not exert any significant antitumor effect. These
      results, along with histological studies from mice receiving AG and IFN-gamma,
      indicated that activation and recruitment of liver macrophages may be a part of
      the mechanism responsible for the inhibition of metastatic growth observed in
      this study.

PMID- 9581678
TI  - Glutathione protects metastatic melanoma cells against oxidative stress in the
      murine hepatic microvasculature.
AB  - Calcein-labeled B16 melanoma (B16M) cells were injected intraportally, and in
      vivo video microscopy was used to study the distribution and damage of cancer
      cells arrested in the liver microvasculature over a period of 4 hours. The
      contribution of glutathione (GSH)-dependent antioxidant machinery to the possible
      oxidative stress-resistance mechanism of B16M cell was determined by in vitro
      incubation with the selective inhibitor of GSH synthesis L-buthionine (S,R)
      sulphoximine (BSO) before B16M cell injection in untreated and 0.5-mg/kg
      lipopolysaccharide (LPS)-treated mice. In addition, untreated and LPS-treated
      isolated syngeneic hepatic sinusoidal endothelial cells (HSE) were used to
      determine in vitro their specific contribution to B16M cell damage. Trauma
      inherent to intrasinusoidal lodgement damaged 35% of B16M cells in both normal
      and LPS-treated mouse liver. The rest of the arrested B16M cells remained intact
      in normal liver for at least 4 hours, although their damaged cell percentage
      significantly (P < .05) increased since the second hour in normal mice injected
      with BSO-treated cells and since the first hour in LPS-treated mice given
      untreated cells. Recombinant human interleukin-1 receptor antagonist (rHuIL-1-Ra)
      given to mice 15 minutes before LPS significantly (P < .05) abrogated B16M cell
      damage. On the other hand, 40% of the B16M cells co-cultured with unstimulated
      HSE and 70% of the co-cultured with LPS-treated HSE became sensitive to
      endothelial cell-mediated damage after BSO treatment. These results demonstrate
      that a high intracellular level of GSH protects B16M cells from possible in vivo
      and in vitro sinusoidal cell-mediated oxidative stress, contributing to the
      mechanism of metastatic cell survival within the hepatic microvasculature.

PMID- 9581679
TI  - pp60c-src activation in hepatocellular carcinoma of humans and LEC rats.
AB  - For the related Src kinases, a close correlation exists between elevated tyrosine
      kinase activity and cell transformation. However, the involvement of pp60c-src in
      hepatocellular carcinoma (HCC) remains obscure. The aim of this study was to
      evaluate whether pp60c-src tyrosine kinase activity is elevated in HCC. We
      analyzed the kinase activity of pp60c-src in normal liver tissue, chronic
      hepatitis liver tissue, and tumorous and adjacent nontumorous portions of HCC
      tissue from patients and Long-Evans cinnamon (LEC) rats that are known to develop
      liver cancer spontaneously. The kinase activity of pp60c-src was rarely detected
      in the normal human liver tissue and chronic hepatitis liver tissue, but it was
      elevated in tumorous and nontumorous portions of HCC tissue. Furthermore, the
      kinase activity of pp60c-src was significantly elevated in tumorous tissues
      compared with nontumorous tissues. The kinase activity of pp60c-src was also
      higher in poorly differentiated HCC. In addition, the kinase activity of pp60c
      src increased proportionately with the development of HCC of LEC rats. Our
      results suggest that activation of the protooncogene product pp60c-src may play
      an important role in the malignant transformation of hepatocytes in human and LEC
      rats, and that it may be closely related to the histopathological grading of
      human HCC.

PMID- 9581680
TI  - Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the
      functions of cultured rat hepatic stellate cells and Kupffer cells.
AB  - Effects of antioxidants, resveratrol, quercetin, and N-acetylcysteine (NAC) on
      the functions of cultured rat hepatic stellate cells and Kupffer cells were
      studied. These compounds dose-dependently suppressed serum-dependent
      proliferation of stellate cells as determined by [3H]thymidine and 5-bromo-2'
      deoxyuridine uptake. Expression of smooth muscle alpha-actin was suppressed by a
      high dose of resveratrol and quercetin. These phenolic compounds also suppressed
      inositol phosphate metabolism, tyrosine phosphorylation, and mitogen-activated
      protein (MAP) kinase activation in platelet-derived growth factor/BB-stimulated
      stellate cells. Moreover, the phenolic compounds selectively reduced the level of
      cell cycle protein cyclin D1 in stellate cells. Thus, resveratrol and quercetin
      might inhibit stellate cell activation by perturbing signal transduction pathway
      and cell cycle protein expression, whereas mechanism of potent antiproliferative
      effect of NAC remains to be elucidated. On the other hand, kinetic analysis
      showed that production of nitric oxide (NO) and tumor necrosis factor alpha (TNF
      alpha) by lipopolysaccharide-stimulated Kupffer cells was strongly inhibited by
      resveratrol and quercetin but not by NAC. Although expression of messenger RNAs
      for inducible NO synthase and TNF-alpha was not affected by the phenolic
      compounds, cellular levels of inducible NO synthase and TNF-alpha secretion were
      suppressed significantly, indicating the posttranscriptional process of
      generating these proteins might be affected predominantly by these phenolic
      compounds. Thus, NAC and these phenolic compounds may have therapeutic potential
      against liver injury by regulating functions of hepatic stellate cells and
      Kupffer cells.

PMID- 9581681
TI  - Characterization of the IGF axis components in isolated rat hepatic stellate
      cells.
AB  - The insulin-like growth factors I and II (IGF-I, -II) are circulating peptides
      known to participate in the regulation of metabolism, growth, and cellular
      differentiation. In the present study, "early cultured" (days 2-3 of culture) and
      "culture-activated" (days 6-7 of culture) rat hepatic stellate cells (HSCs) were
      analyzed for expression of individual components of the IGF axis. Northern blot
      analysis of IGF-I messenger RNA (mRNA) revealed transcripts of 7.5, 4, 2, and 1.0
      to 1.5 kb in culture-activated HSCs, while early cultured HSCs did not express
      IGF-I mRNA. In culture-activated HSCs, an IGF-I secretion of 8.3+/-2.5 ng/10(6)
      cells per 24 hours was determined radioimmunologically. In media from early
      cultured HSCs, IGF-I was not detectable. The IGF-I receptor (IGF-I-R) mRNA
      expression was three-fold higher in early cultured HSCs than in culture-activated
      HSCs. By immunohistochemistry, a decrease of IGF-I-R expression of HSCs in vivo
      following CCl4-induced liver damage was noted as well. IGF binding proteins
      (IGFBPs) were detected in conditioned media from HSCs by 125I-IGF-I ligand
      blotting at apparent molecular masses of 24 and 41 to 45 kd that were
      immunologically identified as IGFBP-4 and -3, respectively. Synthesis of these
      IGFBPs increased with time of culture. At neutral pH, no IGFBP proteolysis was
      observed in conditioned media of early cultured and culture-activated HSCs,
      whereas at acidic pH, protease activities against IGFBP-3 and -4 were detectable.
      IGFBP protease activities were completely abolished by inhibitors of aspartyl and
      cysteine proteases. Addition of 100 nmol/L IGF-I stimulated cell proliferation of
      early cultured HSCs 5.6+/-1.1- and 4.6+/-0.2-fold as measured by [3H]thymidine
      and 5-bromo-2'-deoxyuridine incorporation, respectively. In culture-activated
      HSCs, proliferation was increased 1.2+/-0.1-fold in the presence of 100 nmol/L
      IGF-I in both proliferation assays. It can be concluded that due to a higher
      expression of the IGF-I-R and lower levels of IGFBPs, early cultured HSCs are
      more susceptible to the mitogenic actions of IGFs than the culture-activated
      HSCs. The present data suggest a role for the IGF axis components in the
      initiation rather than the perpetuation of HSC proliferation during hepatic
      fibrogenesis.

PMID- 9581682
TI  - Inhibition of NFkappaB in activated rat hepatic stellate cells by proteasome
      inhibitors and an IkappaB super-repressor.
AB  - The hepatic stellate cell (HSC), following a fibrogenic stimulus, is transformed
      from a quiescent to an activated cell. Cytokines induce NFkappaB activity in
      activated but not in quiescent HSCs with subsequent expression of NFkappaB
      responsive genes, such as intercellular adhesion molecule (ICAM)-1 and
      interleukin (IL)-6. We investigated the effect of proteasome inhibitors and an
      IkappaB super-repressor on the cytokine mediated activation of NFkappaB, ICAM-1,
      and IL-6 in activated HSCs. Culture-activated HSCs were stimulated with IL-1beta
      or tumor necrosis factor alpha (TNFalpha) in the presence or absence of
      proteasome inhibitors, ALLN or MG-132, or after infection with an adenovirus
      expressing the IkappaB super-repressor (Ad5IkappaB) or beta-galactosidase
      (Ad5LacZ) as a control. NFkappaB activity was evaluated by immunofluorescence and
      by electrophoretic mobility shift assay. The steady state level of cytoplasmic
      IkappaB protein was measured by Western Blot. ICAM-1 and IL-6 expression was
      measured by reverse transcriptase-polymerase chain reaction and enzyme-linked
      immunosorbant assay. Proteasome inhibitors, which block the degradation of
      IkappaB, and the Ad5IkappaB, which provides an exogenous nondegradable IkappaB,
      block the stimulation of NFkappaB activity by TNFalpha and IL-1beta in activated
      HSCs. These reagents block the subsequent nuclear translocation of p65 NFkappaB
      and induction of ICAM-1 and IL-6 by cytokines. The specificities of the
      proteasome inhibitors and the IkappaB super-repressor are demonstrated by their
      failure to block c-Jun N-terminal kinase induction by cytokines. Cytokine-induced
      stimulation of NFkappaB, ICAM-1, and IL-6 is blocked by proteasome inhibitors and
      Ad5IkappaB in activated HSCs. Inhibition of IkappaBalpha degradation is a
      potential target for anti-inflammatory therapy in the liver and might influence
      the activation process of HSCs following fibrotic stimuli.

PMID- 9581683
TI  - Interleukin 1beta and interleukin 6, but not tumor necrosis factor alpha, inhibit
      insulin-stimulated glycogen synthesis in rat hepatocytes.
AB  - Recent evidence indicates that inflammatory cytokines are involved in changes of
      blood glucose concentrations and hepatic glucose metabolism in infectious
      diseases, including sepsis. However, little is known regarding how cytokines
      interact with glucoregulatory hormones such as insulin. The objective of the
      present study is to investigate if and how cytokines influence insulin-stimulated
      glycogen metabolism in the liver. Interleukin 1beta (IL-1beta) and interleukin 6
      (IL-6) markedly inhibited the increase of glycogen deposition stimulated by
      insulin in primary rat hepatocyte cultures; however, tumor necrosis factor alpha
      had no effect. Labeling experiments revealed that both cytokines counteracted
      insulin action by decreasing [14C]-glucose incorporation into glycogen and by
      increasing [14C]-glycogen degradation. Furthermore, it was discovered that IL
      1beta and IL-6 inhibited glycogen synthase activity and, in contrast, accelerated
      glycogen phosphorylase activity. In experiments with kinase inhibitors,
      serine/threonine kinase inhibitor K252a blocked IL-1beta- and IL-6-induced
      inhibitions of glycogen deposition, as well as glycogen synthase activity,
      whereas another kinase inhibitor staurosporine blocked only IL-6-induced
      inhibition. Tyrosine kinase inhibitor herbimycin A blocked only IL-1beta-induced
      inhibition. These results indicate that IL-1beta and IL-6 regulate insulin
      stimulated glycogen synthesis through different pathways involving protein
      phosphorylation in hepatocytes. They may mediate the change of hepatic glucose
      metabolism under pathological and even physiological conditions by modifying
      insulin action in vivo.

PMID- 9581684
TI  - Zonated expression of cytokines in rat liver: effect of chronic ethanol and the
      cytochrome P450 2E1 inhibitor, chlormethiazole.
AB  - The release of proinflammatory cytokines by endotoxins and during oxidative
      stress is considered to be an early key step in the pathogenesis of alcoholic
      liver disease (ALD). Ethanol-inducible cytochrome P450 2E1 (CYP2E1) has
      potentially pro-oxidative and toxicological properties, and its expression is
      restricted to the perivenous region of liver. We investigated zonal differences
      of cytokine expression in rat liver and how these are affected by alcohol
      exposure and by chlormethiazole (CMZ), a transcriptional and posttranslational
      inhibitor of hepatic CYP2E1. Periportal and perivenous cell lysates were obtained
      by the digitonin pulse technique from livers of rats treated with ethanol and CMZ
      for 38 days. Cytokine expression on the mRNA and protein levels was quantified
      using competitive polymerase chain reaction (PCR) and Western blot, respectively.
      Chronic ethanol treatment significantly increased the expression of CYP2E1,
      microsomal p-nitrophenol hydroxylase activity (indicative for CYP2E1 enzyme
      activity), and the expression of transforming growth factor beta1 (TGF-beta1),
      tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-1beta (1.4- to 4.6
      fold). In contrast, ethanol caused a decrease in IL-4 expression and had no
      influence on IL-6 expression. CMZ treatment caused a reduction in hepatic CYP2E1
      expression and in the ethanol-induced cytokine expression by 40% to 60%.
      Expression of IL-6, IL-2, and IL-4 mRNA occurred preferentially in the periportal
      region, whereas ethanol caused a pronounced increase in the perivenous expression
      of TGF-beta1, which was inhibited by CMZ as monitored both on the mRNA and
      protein levels. These results show the zonated expression of several cytokines
      and the counteraction of CMZ on all effects of ethanol on cytokine expression.
      The data further strengthen a link between increased CYP2E1 expression and
      enhanced cytokine expression as important events in the development of ALD.

PMID- 9581685
TI  - Time course study of the influence of acute iron overload on Kupffer cell
      functioning and hepatotoxicity assessed in the isolated perfused rat liver.
AB  - This study tested the hypothesis that acute iron overload (500 mg/kg) alters
      Kupffer cell functioning by promoting free radical reactions associated with the
      respiratory burst of liver macrophages, assessed in the isolated perfused rat
      liver under conditions of Kupffer cell stimulation by carbon infusion and
      inactivation by gadolinium chloride pretreatment. Total serum and hepatic iron
      levels were markedly enhanced compared with control values 2 to 24 hours after
      iron treatment. Total liver O2 uptake progressively increased by iron overload
      reaching a maximum at 6 hours after treatment, an effect that was completely
      blocked by GdCl3. Concomitantly, carbon-induced GdCl3-sensitive liver O2 uptake
      was either enhanced by 119% at 2 hours after iron overload, diminished compared
      with control values at 4 hours, or abolished at 6 hours. Iron-overloaded rats
      showed a marked increase in liver sinusoidal lactate dehydrogenase efflux at 4
      and 6 hours after treatment, an effect that is exacerbated by carbon infusion and
      reduced (69%-89%) by GdCl3 pretreatment. Both basal and carbon-induced lactate
      dehydrogenase effluxes returned to control values at 24 hours after iron overload
      concomitantly with depression of the basal O2 uptake, without development of iron
      induced GdCl3-sensitive respiration or Kupffer cell activation by carbon
      infusion. It is concluded that iron overload induces a derangement in the Kupffer
      cell functional status represented by early increases in macrophage-dependent
      respiratory activity, which may contribute to the concomitant liver injury that
      developed and to the impairment of both hepatic respiration and the macrophage
      response to particle stimulation observed at later times after treatment.

PMID- 9581686
TI  - Increased lipid peroxidation and impaired antioxidant enzyme function is
      associated with pathological liver injury in experimental alcoholic liver disease
      in rats fed diets high in corn oil and fish oil.
AB  - Increased hepatic oxidative stress with ethanol administration is hypothesized to
      be caused either by enhanced pro-oxidant production or decreased levels of
      antioxidants or both. We used the intragastric feeding rat model to assess the
      relationship between hepatic antioxidant enzymes and pathological liver injury in
      animals fed different dietary fats. Male Wistar rats (5 per group) were fed
      ethanol with either medium-chain triglycerides (MCTE), palm oil (PE), corn oil
      (CE), or fish oil (FE). Control animals were fed isocaloric amounts of dextrose
      instead of ethanol with the same diets. The following were evaluated in each
      group: liver pathology, lipid peroxidation, manganese superoxide dismutase
      (MnSOD) levels, copper-zinc SOD (CuZnSOD) levels, glutathione peroxidase (GPX)
      levels, and catalase (CAT) levels. All enzymes were evaluated using activity
      assays and immunoblots. Rats fed FE showed the most severe pathology (fatty
      liver, necrosis, and inflammation), those fed CE showed moderate changes, those
      fed PE showed fatty liver only, and those fed MCTE were normal. Parameters
      indicative of lipid peroxidation (conjugated dienes and thiobarbituric acid
      reactive substances) were also greater in rat livers from animals fed the diets
      high in polyunsaturated fatty acids (CE and FE). CuZnSOD, GPX, and CAT activities
      showed an inverse correlation (r=-.92, P < .01) with severity of pathological
      injury, with the lowest levels for both enzymes found in FE-fed rats. Decreased
      enzyme activity in CE- and FE-fed rats was accompanied by similar decreases in
      immunoreactive protein. Ethanol administration did not cause significant
      decreases in enzyme activity in groups that showed no necroinflammatory changes
      (MCTE and PE). MnSOD activity showed no significant change in any ethanol-fed
      group. Our results show that decreases in CuZnSOD, GPX, and CAT occur in rats
      showing pathological liver injury and also having the highest levels of lipid
      peroxidation. These results suggest that feeding dietary substrates that enhance
      lipid peroxidation can exacerbate both ethanol-induced oxidative damage as well
      as necroinflammatory changes. The decrease in activity of antioxidant enzymes
      observed in animals fed diets high in polyunsaturated fatty acids and ethanol
      could possibly increase the susceptibility to oxidative damage and further
      contribute to ethanol-induced liver injury.

PMID- 9581687
TI  - Cyclic adenosine monophosphate-mediated protection against bile acid-induced
      apoptosis in cultured rat hepatocytes.
AB  - Cyclic adenosine monophosphate (cAMP) has been shown to modulate apoptosis. To
      evaluate the role of cAMP in bile acid-induced hepatocyte apoptosis, we studied
      the effect of agents that increase cAMP on the induction of apoptosis by
      glycochenodeoxycholate (GCDC) in cultured rat hepatocytes. GCDC induced apoptosis
      in 26.5%+/-1.1% of hepatocytes within 2 hours. Twenty-minute pretreatment of
      hepatocytes with 100 micromol/L 8-(4-chlorothiophenyl) cAMP (CP-cAMP) resulted in
      a reduction in the amount of apoptosis to 35.2%+/-3.8% of that seen in
      hepatocytes treated with GCDC alone. Other agents that increase intracellular
      cAMP, including dibutyryl cAMP (100 micromol/L), glucagon (200 nmol/L), and a
      combination of forskolin (20 micromol/L) and 3-isobutyl-1-methylxanthine (20
      micromol/L), also inhibited GCDC-induced apoptosis to a similar extent.
      Pretreatment with the protein kinase A (PKA) inhibitor, KT5720, prevented the
      protective effect of CP-cAMP and inhibited CP-cAMP-induced activation of PKA
      activity. Inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin (50
      nmol/L), or Ly 294002 (20 micromol/L) also prevented the cytoprotective effect of
      cAMP. PI3K assays confirmed that wortmannin (50 nmol/L) inhibited PI3K activity,
      while CP-cAMP had no effect on the activity of this lipid kinase. GCDC increased
      mitogen-activated protein kinase (MAPK) activity, but had no effect on stress
      activated protein kinase (SAPK) activity in hepatocytes. cAMP decreased basal and
      GCDC-induced MAPK activity and increased SAPK activity. The MAPK kinase
      inhibitor, PD 98059, inhibited both GCDC-mediated MAPK activation and GCDC
      induced apoptosis. IN CONCLUSION: 1) agents that increase intracellular cAMP
      protect against hepatocyte apoptosis induced by hydrophobic bile acids; 2)
      activation of MAPK by GCDC may be involved in bile acid-induced apoptosis; and 3)
      cAMP-mediated cytoprotection against bile acid-induced apoptosis appears to
      involve PKA, MAPK, and PI3K.

PMID- 9581688
TI  - The effect of N-acetylcysteine on oxygen transport and uptake in patients with
      fulminant hepatic failure.
AB  - We have investigated the effect of N-acetylcysteine on hemodynamic variables,
      oxygen delivery (DO2), oxygen consumption (VO2), and oxygen extraction in
      patients with fulminant hepatic failure using independent methods of determining
      DO2 and VO2, thereby eliminating the effect of mathematical coupling, which may
      have biased previous studies. In 11 patients with severe fulminant hepatic
      failure, we documented the hemodynamic effects of N-acetylcysteine during the
      first 5 hours of a standard infusion regime and simultaneously measured VO2 using
      a method based on respiratory gas analysis. We related physiological changes to
      plasma N-acetylcysteine concentrations, and compared this group with 7 patients
      who received placebo infusions. A variable hemodynamic response to N
      acetylcysteine was observed that did not differ significantly in comparison with
      the placebo group, and did not correlate with plasma drug concentrations. The
      most significant relationship observed between DO2 and VO2 in any patient
      predicted a 13-mL x min(-1) x m(-2) increase in VO2 when DO2 increased by 100 mL
      x min(-1) x m(-2); in 8 patients, VO2 was independent of DO2 over the range
      observed. In the group that received N-acetylcysteine, a small (mean 6 [SD 6] mL
      x min(-1) x m[-2]) increase in VO2 occurred in comparison with baseline after 1
      hour of infusion (P < .01), but changes were not significantly different from the
      placebo group and were not sustained. N-Acetylcysteine infusion did not increase
      oxygen extraction or result in an improvement in whole-blood lactate levels or
      base excess during the study period. We conclude that N-acetylcysteine infusion
      does not result in clinically relevant improvements in global VO2, or in clinical
      markers of tissue hypoxia in patients with severe fulminant hepatic failure.

PMID- 9581689
TI  - Chylomicrons alter the hepatic distribution and cellular response to endotoxin in
      rats.
AB  - Chylomicrons (CM) can bind endotoxin (lipopolysaccharide [LPS]), forming CM-LPS
      complexes, and protect against endotoxic shock and death in rodent models of gram
      negative sepsis. The liver appears to play a central role in this process, as
      demonstrated by the increased uptake of LPS by this organ. We examined the effect
      of CM on the uptake and cellular response to injected 125I-LPS by hepatocytes and
      hepatic nonparenchymal cells. Whereas CM increased the uptake of LPS by both
      hepatocytes and Kupffer cells, the increase was proportionately greater in
      hepatocytes than Kupffer cells. Importantly, CM-LPS complexes inhibited inducible
      nitric oxide synthase (iNOS) mRNA expression and NO production in Kupffer cells
      and endothelial cells, reducing mRNA levels by 45% to 50% as compared with LPS
      alone. CM-bound LPS also reduced NO production by hepatocytes in response to
      cytokine stimulation. Lastly, CM-LPS complexes yielded a concentration-dependent
      inhibition of LPS-induced tumor necrosis factor alpha (TNF-alpha) production by
      Kupffer cells in vitro. These data indicate that the mechanism by which CM
      protect against endotoxicity may involve an increased uptake of LPS by
      hepatocytes. Moreover, uptake of CM-bound LPS by liver cells attenuates the
      capacity of these cells to respond to proinflammatory stimulation. These results
      highlight important anti-inflammatory properties of CM.

PMID- 9581690
TI  - Hepatic venous hemoglobin oxygen saturation predicts regenerative status of
      remnant liver after partial hepatectomy in rats.
AB  - This study was designed to evaluate the use of hepatic venous hemoglobin oxygen
      saturation (ShVO2) as an indicator of hepatic oxygen supply-demand relation and
      also regenerative status of the liver after partial hepatectomy in rats. We
      assessed the ShVO2 levels for 7 days, as well as hepatic hemodynamics, oxygen
      consumption, DNA synthesis and energy charge of the remnant liver for 3 days
      after 50% hepatectomy or sham operation. Total hepatic oxygen consumption (HVO2)
      per liver weight, hepatic oxygen extraction ratio (HO2ER), and DNA synthesis were
      significantly elevated at days 1 and 3 after hepatectomy, compared with the
      preoperative levels. Meanwhile, significantly decreased ShVO2 levels were
      observed at days 1 and 3, and the ShVO2 levels were significantly correlated with
      the HVO2. Furthermore, the decreased ShVO2 levels were synchronized with the
      increased DNA synthesis in the remnant liver. Energy charge levels were also
      significantly decreased at day 1 after hepatectomy. These results suggest that
      the regenerating liver demands an increased amount of oxygen for mitochondrial
      oxidative phosphorylation to restore hepatic energy charge. In conclusion, the
      ShVO2 after hepatectomy may reflect oxygen metabolic status in the remnant liver
      and could be useful for estimating liver regeneration.

PMID- 9581691
TI  - Hepatocyte growth factor stimulates synthesis of lipids and secretion of
      lipoproteins in rat hepatocytes.
AB  - We have reported that infusion of recombinant human hepatocyte growth factor
      (rhHGF) stimulates liver regeneration after hepatectomy in cirrhotic rats and
      increases the level of serum lipids and secretion of very-low density lipoprotein
      (VLDL). Studies were now performed to determine whether rhHGF directly influences
      lipid synthesis and its secretion in cultured rat hepatocytes. Isolated cells
      were cultured in the presence or absence of rhHGF (20 ng/mL) for 2 days. During
      the first 12 hours, rhHGF transiently inhibited the release of lipids
      (triacylglycerol, total cholesterol, and phospholipids), but stimulated their
      releases with maximal levels achieved at 36 hours. [3H]-glycerol experiment with
      the transcriptional and translational inhibitors revealed that rhHGF stimulated
      de novo synthesis of lipids by affecting activities of lipid metabolic gene.
      [35S]-Methionine experiment also revealed de novo synthesis of apolipoprotein B
      by rhHGF. Furthermore, lipid analysis of lipoprotein fractions in the conditioned
      medium showed that rhHGF enhanced levels of triacylglycerol, total cholesterol,
      and phospholipids by 50% to 200% in both VLDL and low-density lipoproteins
      (LDL)/high-density lipoprotein (HDL). Genistein, a tyrosine kinase inhibitor,
      blocked the secretion of VLDL, as well as synthesis of lipids and apolipoprotein
      B stimulated by rhHGF. These results indicate that HGF likely stimulates lipid
      biosynthesis and lipoprotein secretion in hepatocytes through its tyrosine kinase
      associated receptor, c-met, and accelerates the progress of cell maturation in
      liver regeneration.

PMID- 9581692
TI  - Thrombin activates two stress-activated protein kinases, c-Jun N-terminal kinase
      and p38, in HepG2 cells.
AB  - Recently identified c-Jun N-terminal kinase (JNK) and p38 mitogen-activated
      protein kinase are activated by stimuli of various cellular stresses, cytokines,
      and growth factors. Strong activation of JNK was reported in the regenerating
      liver, implicating JNK in growth stimulation of hepatocytes. However, it is not
      known which factors regulate JNK activity in liver cells. In this study, we
      examined activation of JNK and p38 in HepG2 cells stimulated with heterotrimeric
      G protein-coupled receptor agonists known as mitogens. Thrombin, lysophosphatidic
      acid (LPA), and bradykinin (BK) stimulated extracellular signal-regulated protein
      kinase to similar extents, indicating that HepG2 cells have cell surface
      receptors for these agonists, which are coupled to intracellular signaling
      pathways. In contrast, only thrombin strongly activated JNK and p38. Thrombin
      induced activation of JNK and p38 peaked at 30 minutes and 15 minutes with
      maximal stimulation of 13- and 4-fold increases, respectively. LPA and BK failed
      to activate JNK at all and activated p38 only slightly. Interestingly, thrombin
      induced JNK activation was inhibited by protein kinase C down-regulation and the
      addition of a specific protein kinase C inhibitor. Short-term stimulation of
      cells with an active phorbol ester also induced JNK activation in HepG2 cells.
      These results indicate that thrombin is a relatively strong activator for JNK and
      p38 and might play a role in the regulation of activities of JNK and p38 in liver
      cells.

PMID- 9581693
TI  - Oral tolerization to adenoviral proteins permits repeated adenovirus-mediated
      gene therapy in rats with pre-existing immunity to adenoviruses.
AB  - Exposure to wild-type adenoviruses is common in humans and results in immune
      response against adenoviruses. The pre-existing antibodies and a strong secondary
      humoral and cellular immune response would interfere with gene transfer using
      recombinant adenoviral vectors. To test whether the secondary immune response can
      be abrogated by oral tolerization to adenoviral antigens, we immunized bilirubin
      UDP-glucuronosyltransferase (BUGT)-deficient jaundiced Gunn rats with a
      recombinant adenovirus (5 x 10(9) pfu/rat) expressing the human UDP
      glucouronosyltransferase (BUGT1) gene (Ad-hBUGT). Transgene expression was shown
      by reduction of mean serum bilirubin levels from 7.0 mg/dL to 2.3 mg/dL in 14
      days, which then increased gradually to pretreatment levels in 6 weeks. All
      recipients developed antibodies (1:2[10]) and cytotoxic lymphocytes against the
      adenovirus. For oral tolerization, we administered to the immunized rats protein
      extracts of a recombinant adenovirus type 5 (1-1.5 mg/day) via duodenostomy tubes
      10 to 40 days after the initial virus injection; control rats received bovine
      serum albumin. In rats fed adenoviral proteins and the BSA-fed controls, the
      antibody titers decreased to 1:2(7) and 1:2(9), respectively, in 70 days.
      Lymphocytes from the tolerized rats expressed TGF-beta1 upon exposure to antigen
      presenting cells primed with adenoviral antigens, whereas IFN-gamma expression
      was undetectable. In contrast, lymphocytes from the BSA-treated control rats
      expressed IFN-gamma but not transforming growth factor beta1 (TGF-beta1). Seventy
      days after the first injection in the orally tolerized rats, but not in the
      controls, a second Ad-hBUGT injection caused human BUGT1 expression again,
      reducing serum bilirubin levels to those observed after the first injection. In
      the tolerized rats, serum antibody titers and anti-adenoviral cytotoxic
      lymphocyte activities continued to decline despite the second injection, whereas
      the antibody levels were boosted in the non-tolerized group. This results show
      that by preventing the secondary booster response, oral tolerization permits
      repeated adenovirus-directed gene transfer despite the presence of a residual
      antibody titer from a previous adenoviral exposure.

PMID- 9581694
TI  - Persistent viremia after recovery from self-limited acute hepatitis B.
AB  - To define the duration of viremia in the course of acute hepatitis B, we
      semiquantitatively determined the levels of hepatitis B virus (HBV) DNA in the
      sera, using polymerase chain reaction (PCR) coupled with Southern blotting, of
      non-immunocompromised patients with self-limited acute hepatitis B. In the sera
      of 10 of 11 patients, HBV DNA, which was presumably coated with viral proteins,
      was detected for a long period after recovery, even at the final observation
      times, which ranged from 6 to 19 months after disease onset. To characterize the
      mode of HBV that was present in serum, we immunoprecipitated immune complexes in
      sera by the addition of anti-human immunoglobulin G (IgG) and determined the
      levels of HBV DNA separately in the supernatants and pellets. In the acute phase
      of hepatitis B, high levels of HBV DNA were detected both in the supernatants and
      pellets at comparative levels. After the convalescent phase, the amount of HBV
      DNA in the supernatant decreased with respect to that in the pellets. It is
      notable that, in most cases, serum HBV persisted as a form of immune complex even
      after the seroconversion to antibody to hepatitis B surface antigen (anti-HBs).
      These data suggest that the replication of HBV may persist in some organs, most
      likely in the liver or peripheral blood cells, for a long period after recovery
      from acute hepatitis B, and the data indicate the possible transmission of HBV
      from organ transplantation donors who exhibit serological markers of past
      infection only.

PMID- 9581695
TI  - Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized,
      controlled trial.
AB  - Thymosin alpha1 (Talpha) is an immune modifier that has been shown in a pilot
      study to be effective for chronic hepatitis B; this requires confirmation. Ninety
      eight patients with clinicopathologically proven chronic hepatitis B were
      randomly allocated to 3 groups: 1) group A received a 26-week course of Talpha
      with a 1.6-mg subcutaneous injection two times a week (T6 group); 2) group B
      received the same regimen as group A, but Talpha therapy extended for 52 weeks
      (T12 group); and 3) group C served as a control group and was followed up for 18
      months without specific treatment (T0 group). The three groups were comparable in
      clinicohistological features at entry. The complete virological response rate
      (clearance of serum hepatitis B virus [HBV] DNA and hepatitis B e antigen
      [HBeAg]) was higher in group A (40.6%) and group B (26.5%) than in group C (9.4%)
      (group A vs. group C: P=.004; group B vs. group C: P=.068) when assessed 18
      months after entry, although complete response rates among these three groups
      were similar when first assessed at the end of therapy. There was a trend for
      complete virological response to increase or accumulate gradually after the end
      of Talpha therapy. None of the responders lost hepatitis B surface antigen.
      Blinded histological assessment showed a significant improvement in treated
      patients, particularly in lobular necroinflammation and scores excluding
      fibrosis. No significant side effects were observed. These results suggest that a
      26-week course of Talpha therapy is effective and safe in patients with chronic
      hepatitis B.

PMID- 9581696
TI  - Characteristics of patients with hepatitis C virus with and without GB virus
      C/hepatitis G virus co-infection and efficacy of interferon alfa.
AB  - GB virus C/hepatitis G virus (GBV-C/HGV) infection seems to be common among
      patients with hepatitis C virus (HCV) infection. We studied retrospectively the
      proportions of patients with GBV-C/HGV RNA and antibodies to the GBV-C/HGV second
      envelope protein (anti-E2) among 149 subjects with chronic hepatitis C who had
      received interferon alfa. The clinical characteristics of patients with GBV-C/HGV
      RNA or anti-E2 were examined, as was the efficacy of the treatment. Stored serum
      specimens were tested for GBV-C/HGV RNA by the reverse transcription polymerase
      chain reaction and for anti-E2 by an enzyme-linked immunosorbent assay. Of the
      149 patients before therapy, 8 (5%) had GBV-C/HGV RNA only, 72 (48%) had anti-E2
      only, and 4 (3%) had both. The mean age of patients with GBV-C/HGV RNA (some with
      anti-E2) was significantly less than that of patients with anti-E2 only. Results
      of laboratory and histological evaluations were not different depending on the
      presence of GBV-C/HGV RNA or anti-E2. The GBV-C/HGV RNA titer decreased during
      therapy in all 12 patients with GBV-C/HGV RNA; only 4, with a low titer before
      therapy and with anti-E2 detected at some time, had sustained clearance of GBV
      C/HGV. Our results suggested that half of the patients with chronic hepatitis C
      had been exposed to GBV-C/HGV, but in almost all, the virus had been cleared;
      also, even chronic GBV-C/HGV infection did not affect the severity of the disease
      arising from HCV. Interferon alfa treatment was sometimes effective against GBV
      C/HGV, and anti-E2 may be associated with clearance of GBV-C/HGV.

PMID- 9581698
TI  - A randomized study comparing ribavirin and interferon alfa monotherapy for
      hepatitis C recurrence after liver transplantation.
AB  - Hepatitis C virus (HCV) infection usually recurs after orthotopic liver
      transplantation (OLT), and most patients develop graft damage. This study
      compared the efficacy of interferon alfa (IFN-alpha) and ribavirin monotherapies
      in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT
      recipients with chronic hepatitis C were randomized to receive either IFN-alpha
      (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks.
      Virological, biochemical, and histological responses to treatment were assessed.
      Twenty-eight patients completed the treatment regimen, two ribavirin-treated
      patients being withdrawn because of severe hemolysis. Normalization of serum
      aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin
      (93%) and 6 of 14 patients receiving IFN-alpha (43%; P=.01). Lobular inflammation
      was reduced in 9/14 ribavirin-treated (64%) and 3 of 14 IFN-alpha-treated
      patients (21%; P=.05), each of whom had a biochemical response. However, the
      total histological activity index did not improve in either the interferon
      (P=.43) or the ribavirin (P=.96) group. Posttreatment viremia levels were
      significantly reduced in IFN-alpha-treated (P=.05) but not in ribavirin-treated
      (P=.88) patients. Hemolysis occurred in all ribavirin-treated patients, with
      serum hemoglobin decreasing to < 10 g/dL in 50%. Total leukocyte and lymphocyte
      counts decreased significantly during ribavirin treatment (P=.02 and P=.004,
      respectively). We concluded that in patients with chronic hepatitis C after OLT,
      IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving
      normalization of serum aspartate aminotransferase levels and reducing lobular
      inflammation, but not the total histological activity index. These findings
      provide a rationale for combination therapy in the post-OLT setting, although
      patients must be carefully monitored for hemolysis.

PMID- 9581697
TI  - Risk factors for hepatocellular carcinoma and its incidence after interferon
      treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group.
AB  - To elucidate the risk factors for liver carcinogenesis and to examine the
      incidence of hepatocellular carcinoma (HCC) after interferon therapy, 1,022
      chronic hepatitis C patients treated with interferon were followed by
      ultrasonography for 13 to 97 months (median 36 months). Sustained response with
      prolonged alanine aminotransferase normalization was found in 313 patients,
      transient response with alanine aminotransferase relapse after therapy in 304,
      and no response in 405. Forty-six developed HCC, of whom 5 were sustained
      responders, 9 were transient responders, and 32 were nonresponders. The
      cumulative incidence of HCC in transient responders was almost equal to that in
      sustained responders, and it was significantly higher in nonresponders than in
      sustained and transient responders (P=.0009). The seventh-year cumulative
      incidence rates of HCC in sustained responders, transient responders, and
      nonresponders were estimated to be 4.3%, 4.7%, and 26.1%, respectively. However,
      there was no significant difference in the cumulative incidence of HCC between
      patients with HCV subtype 1 and 2 (P=.14). Cox regression analysis showed that
      the risk of HCC development was not elevated in transient responders compared
      with sustained responders, but that the risk was 7.90-fold higher in
      nonresponders than in sustained responders (P=.008). Patients > or =55 years of
      age had a significantly higher risk ratio (4.65) than did those under 55 years of
      age (P=.006). The risk of HCC development in men was 4.35 times higher than the
      risk in women (P=.02). However, the degree of fibrosis was not a significant risk
      factor for the development of HCC (risk ratio, 3.16; P=.052). These results
      suggest that patients in the high-risk group of HCC after interferon therapy were
      those who showed no response, those who were older, and those who were male, and
      that such patients should be carefully followed using ultrasonography.

PMID- 9581699
TI  - The GDPAL region of the pre-S1 envelope protein is important for morphogenesis of
      woodchuck hepatitis virus.
AB  - The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region,
      Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and
      secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino
      acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV)
      form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles
      the DDPLL sequence of DHBV. To determine whether the GDPAL region was
      functionally equivalent to the DDPLL region, we deleted this region from the pre
      S protein of WHV or mutated individual amino acids within the region. The mutant
      DNA was transfected into human hepatoma cell line Huh7, and the medium was
      assayed for virion production by immunoprecipitation and Southern blot analysis.
      We found that an in-frame deletion of this small region inhibited virion
      formation, suggesting that the GDPAL region of the pre-S envelope protein was
      required for virus assembly and/or secretion of WHV. Individual replacement of
      alanine 204, leucine 205, or serine 206 with other amino acid residues did not
      affect virus production. However, substitution of either aspartic acid 202 with
      valine or proline 203 with leucine dramatically inhibited WHV production.
      Furthermore, the GDPAL mutants were individually tested for their abilities to
      complement a pre-S1 defective genome. The results showed that the GDPAL region
      functioned as part of the pre-S1 protein but was not required to function as part
      of the pre-S2 protein.

PMID- 9581700
TI  - The impact of traveling to endemic areas on the spread of hepatitis E virus
      infection: epidemiological and molecular analyses.
AB  - Traveling to endemic areas carries a risk of hepatitis E virus (HEV) infection,
      but no molecular analysis to document sources of infection is available. Eighteen
      (38%) of 47 patients with acute non-A, non-B, non-C hepatitis were positive for
      antibody to HEV (anti-HEV), and 9 (50%) of these were also positive for serum HEV
      RNA by polymerase chain reaction following reverse transcription. Only 1 (5%) of
      the 21 patients with acute hepatitis A was positive for HEV RNA. Travel to
      endemic areas (mostly to China; odds ratio, 22.2; 95% confidence interval, 4.7
      105.8) and deeper jaundice (odds ratio, 5.2; 95% confidence interval, 1.01-27.2)
      were the only factors associated with HEV infection in multivariate analysis. The
      two HEV isolates from two patients who had traveled to China and the HEV isolate
      from a patient whose travel history was obscure formed a monophyletic group with
      the isolates from Guangzhou. The HEV isolates from our patients show a homology
      of 72% to 78% in nucleotide sequence with the Burma, Beijing, India, Pakistan,
      and Xiangjiang strains; a homology of 81% to 91% with the Guangzhou strains; and
      a homology of 76% with the Mexico strain. The close relationship between the
      Taiwan isolates and the Guangzhou strains was further supported by the short
      Kimura's two-parameter distances among them. In summary, HEV infection does occur
      in this area. Epidemiological and molecular analyses strongly indicate that most
      cases of HEV infection originated from travel to HEV-endemic areas.

PMID- 9581701
TI  - Neurovisual impairment: a frequent complication of alpha-interferon treatment in
      chronic viral hepatitis.
AB  - Following our earlier observation of clinically evident optic tract neuropathy in
      patients receiving low-dose interferon (IFN) therapy, we prospectively evaluated
      53 consecutive patients treated for chronic hepatitis B or C with a median dose
      of 3 MU of IFN-a2b thrice weekly. Measurements included routine ophthalmologic
      evaluation and recordings of visual evoked responses (VER), electroretinograms
      (ERG), visual acuity, and visual fields, before, at the end of IFN treatment, and
      at follow-up visits. Baseline P100 latencies of VERs (base-VER) were abnormally
      prolonged in 24 patients (32 of 106 eyes, 30.2%); age was the only significant
      covariate associated with increased risk for an abnormal base-VER by multiple
      logistic regression (relative risk [RR] 5.3 per each 5-year increase in age). In
      45 patients (74 eyes) with normal baseline P100 latencies, the end-of-treatment
      VERs (end-VER) were significantly prolonged compared with baseline, becoming
      abnormal in 11 (15 of 74 eyes, 20.3%) (138.8+/-8.7 vs. 117.7+/-5.2 ms, P < .001).
      This subgroup had older age (59.1+/-11.0 vs. 47.5+/-15.3, P=.007) and reduced
      visual sensitivity compared with their own pretreatment measurements (24.5+/-1.6
      vs. 23.0+/-1.2db, P=.019). Changes of end-VERs by age had a sigmoid distribution
      with a steep increase of values beyond the 5th decade (R2=.326, P < .001). In a
      logistic regression model, significant predictors of abnormal end-VERs were,
      patients' age (RR 5.6 per each 5-year increase), presence of hepatitis B virus
      (HBV) infection (RR 15.1 compared with hepatitis C virus [HCV] infection) and
      serum cholesterol levels above 240 mg% (RR 7.1 compared with values < 240 mg%).
      Subconjunctival hemorrhages were seen in 2 cases and funduscopic examination
      revealed cotton wool spots in one other. ERG recordings and the P100 amplitude
      remained unchanged. After stopping IFN, the treatment-associated neurovisual
      abnormalities reversed to normal in 7 patients (10 of 15 eyes) and persisted in 5
      (5 of 15 eyes, 33.3%) for up to 37 (median 7.3) months observation, all patients
      remaining clinically asymptomatic. In conclusion, subclinical neurovisual
      impairment is a frequent, largely unrecognized complication of low-dose IFN
      therapy, and patients with chronic hepatitis B and older age appear to be most
      susceptible. This apparently innocuous complication is long lasting, possibly
      irreversible in some patients, with yet undetermined consequences on visual
      function.

PMID- 9581702
TI  - Relative quantification and mapping of hepatitis C virus by in situ hybridization
      and digital image analysis.
AB  - Although several reports concerning the detection of hepatitis C virus (HCV) by
      in situ hybridization have been published, there are no data concerning the
      relative viral load in infected hepatocytes or about its relation with serum
      viremia levels. To address these issues, liver biopsies from 10 patients with
      chronic hepatitis C were analyzed by in situ hybridization and digital image
      analysis of hybridization signals. Serum HCV RNA levels were measured using the
      Amplicor Monitor test. HCV RNA was detected by in situ hybridization in the
      hepatocytes of the ten liver samples. The hybridization signals were mainly found
      in the cytoplasm. The relative viral load per infected cell fit the second order
      polynomial curves in all cases. The minimum and maximum relative viral load per
      infected hepatocyte differed in the ten cases; however, large differences were
      not observed in the mean relative viral load among the samples, especially when
      compared with the increasing values detected for copy number per milliliter in
      serum. The percentage of infected cells ranged from 4.8% to 87.6% in the ten
      cases. The percentage of positive cells correlated with the serum viremia levels.
      Our data suggest that HCV viremia does not depend on the relative viral load per
      infected cell but on the number of infected hepatocytes.

PMID- 9581703
TI  - Determinants of outcome of compensated hepatitis C virus-related cirrhosis.
AB  - The aim of this study was to assess the incidence of decompensation (ascites,
      jaundice, variceal bleeding, and encephalopathy), hepatocellular carcinoma (HCC)
      and death or liver transplantation in patients with compensated hepatitis C virus
      (HCV)-related cirrhosis, taking into account the viral genotype and interferon
      (IFN) therapy. Between 1989 and 1994, 668 patients with no clinical evidence of
      decompensation were referred to our department for liver biopsy because of
      positivity for anti-HCV antibodies and elevated aminotransferase activity; 103 of
      these patients had cirrhosis. The median follow-up was 40 months. Fifty-nine
      patients were treated with IFN for a mean duration of 11+/-6 months; 3 (5%) had a
      prolonged biochemical and virological response. Baseline characteristics of IFN
      treated and untreated patients were not significantly different. HCV genotypes
      (InnoLiPa) were predominantly 1b (48%) and 3a (20%). During follow-up,
      complications of cirrhosis occurred in 26 patients, HCC in 11 patients, and
      decompensation not related to HCC in 19 patients. Sixteen patients died, 94% of
      liver disease. Three patients were transplanted for liver failure. The 4-year
      risk of HCC was 11.5% (annual incidence 3.3%) and that of decompensation was 20%.
      Survival probability was 96% and 84% at 2 and 4 years, respectively. In
      multivariate analysis, the absence of IFN therapy was the only independent factor
      predictive both for HCC and decompensation. A low albumin level at entry and the
      absence of IFN therapy were the two independent factors predictive of death or
      liver transplantation. Probability of survival at 2 and 4 years was significantly
      different between IFN-treated and untreated patients (respectively 97% and 92% vs
      95% and 63%, P < .0001). In conclusion, in patients with compensated HCV-related
      cirrhosis: 1) complications of cirrhosis are frequent, whatever the viral
      genotype; and 2) the severity of cirrhosis and the absence of IFN therapy are
      independently predictive of bad outcome.

PMID- 9581704
TI  - Neurovisual complications of interferon-alpha therapy.

PMID- 9581705
TI  - Hepatitis C: somber views of natural history and optimistic views of interferon
      treatment?

PMID- 9581706
TI  - Blocking NF-kappaB in the liver: the good and bad news.

PMID- 9581707
TI  - Life or death: the fate of the hepatic stellate cell following hepatic injury.

PMID- 9581708
TI  - Nitric oxide in hepatopulmonary syndrome.

PMID- 9581709
TI  - Autoantibodies present in chronic hepatitis C and chronic hepatitis B viral
      infections.

PMID- 9581710
TI  - Alveolar echinococcosis.

PMID- 9581711
TI  - Interactive role of infection, inflammation and traditional risk factors in
      atherosclerosis and coronary artery disease.
AB  - Although first suggested at the turn of the 20th century, there is a renewed
      interest in the infectious theory of atherosclerosis. Studies done in many
      laboratories around the world over the past several years have shown an
      association between markers of inflammation and coronary atherosclerosis with an
      exacerbation of the inflammatory process during acute myocardial ischemia,
      particularly in the early stages of reperfusion. It is also being recognized that
      the traditional risk factors, such as smoking, dyslipidemia, hypertension and
      diabetes mellitus, do not explain the presence of coronary atherosclerosis in a
      large proportion of patients. We believe that in certain genetically susceptible
      people, infection with very common organisms, such as Chlamydia pneumoniae or
      cytomegalovirus, may lead to a localized infection and a chronic inflammatory
      reaction. Persistence of infection may relate to the degree of inflammation and
      severity of atherosclerosis. Early trials with appropriate antibiotic agents in
      some patients with a recent history of acute myocardial infarction have led to
      very salutary results. If patients with an infectious basis of atherosclerosis
      can be identified, a therapy directed at eradication of the offending organism
      may be appropriate.

PMID- 9581712
TI  - Seasonal distribution of acute myocardial infarction in the second National
      Registry of Myocardial Infarction.
AB  - OBJECTIVES: This observational study sought to determine whether cases of acute
      myocardial infarction (AMI) reported to the second National Registry of
      Myocardial Infarction (NRMI-2) varied by season. BACKGROUND: The existence of
      circadian variation in the onset of AMI is well established. Examination of this
      periodicity has led to new insights into pathophysiologic triggers of
      atherosclerotic plaque rupture. Although a seasonal pattern for mortality from
      AMI has been previously noted, it remains unclear whether the occurrence of AMI
      also displays a seasonal rhythmicity. Documentation of such a pattern may foster
      investigation of new pathophysiologic determinants of plaque rupture and
      intracoronary thrombosis. METHODS: We analyzed the number of cases of AMI
      reported to NRMI-2 by season during the period July 1, 1994 to July 31, 1996.
      Data were normalized so that seasonal occurrence of AMI was reported according to
      a standard 90-day length. RESULTS: A total of 259,891 cases of AMI were analyzed
      during the study period. Approximately 53% more cases were reported in winter
      than during the summer. The same seasonal pattern (decreasing occurrence of
      reported cases from winter to fall to spring to summer) was seen in men and
      women, in different age groups and in 9 of 10 geographic areas. In-hospital case
      fatality rates for AMI also followed a seasonal pattern, with a peak of 9% in
      winter. CONCLUSION: The present results suggest that there is a seasonal pattern
      in the occurrence of AMIs reported to NRMI-2 that is characterized by a marked
      peak of cases in the winter months and a nadir in the summer months. This pattern
      was seen in all subgroups analyzed as well as in different geographic areas.
      These findings suggest that the chronobiology of seasonal variation in AMI may be
      affected by variables independent of climate.

PMID- 9581713
TI  - A clinical trial comparing primary stenting of the infarct-related artery with
      optimal primary angioplasty for acute myocardial infarction: results from the
      Florence Randomized Elective Stenting in Acute Coronary Occlusions (FRESCO)
      trial.
AB  - OBJECTIVES: This study sought to compare stenting of the primary infarct-related
      artery (IRA) with optimal primary percutaneous transluminal coronary angioplasty
      (PTCA) with respect to clinical and angiographic outcomes of patients with an
      acute myocardial infarction. BACKGROUND: Early and late restenosis or reocclusion
      of the IRA after successful primary PTCA significantly contributes to increased
      patient morbidity and mortality. Coronary stenting results in a lower rate of
      angiographic and clinical restenosis than standard PTCA in patients with angina
      and with previously untreated, noncomplex lesions. METHODS: After successful
      primary PTCA, 150 patients were randomly assigned to elective stenting or no
      further intervention. The primary end point of the trial was a composite end
      point, defined as death, reinfarction or repeat target vessel revascularization
      as a consequence of recurrent ischemia within 6 months of randomization. The
      secondary end point was angiographic evidence of restenosis or reocclusion at 6
      months after randomization. RESULTS: Stenting of the IRA was successful in all
      patients randomized to stent treatment. At 6 months, the incidence of the primary
      end point was 9% in the stent group and 28% in the PTCA group (p=0.003); the
      incidence of restenosis or reocclusion was 17% in the stent group and 43% in the
      PTCA group (p=0.001). CONCLUSIONS: Primary stenting of the IRA, compared with
      optimal primary angioplasty, results in a lower rate of major adverse events
      related to recurrent ischemia and a lower rate of angiographically detected
      restenosis or reocclusion of the IRA.

PMID- 9581714
TI  - Clinical experience with primary percutaneous transluminal coronary angioplasty
      compared with alteplase (recombinant tissue-type plasminogen activator) in
      patients with acute myocardial infarction: a report from the Second National
      Registry of Myocardial Infarction (NRMI-2).
AB  - OBJECTIVES: We sought to compare outcomes after primary percutaneous transluminal
      coronary angioplasty (PTCA) or thrombolytic therapy for acute myocardial
      infarction (MI). BACKGROUND: Primary PTCA and thrombolytic therapy are
      alternative means of achieving reperfusion in patients with acute MI. The Second
      National Registry of Myocardial Infarction (NRMI-2) offers an opportunity to
      study the clinical experience with these modalities in a large patient group.
      METHODS: Data from NRMI-2 were reviewed. RESULTS: From June 1, 1994 through
      October 31, 1995, 4,939 nontransfer patients underwent primary PTCA within 12 h
      of symptom onset, and 24,705 patients received alteplase (recombinant tissue-type
      plasminogen activator [rt-PA]). When lytic-ineligible patients and patients
      presenting in cardiogenic shock were excluded, baseline characteristics were
      similar. The median time from presentation to initiation of rt-PA in the
      thrombolytic group was 42 min; the median time to first balloon inflation in the
      primary PTCA group was 111 min (p < 0.0001). In-hospital mortality was higher in
      patients in shock after rt-PA than after PTCA (52% vs. 32%, p < 0.0001). In
      hospital mortality was the same in lytic-eligible patients not in shock: 5.4%
      after rt-PA and 5.2% after PTCA. The stroke rate was higher after lytic therapy
      (1.6% vs. 0.7% after PTCA, p < 0.0001), but the combined end point of death and
      nonfatal stroke was not significantly different between the two groups (6.2%
      after rt-PA and 5.6% after PTCA). There was no difference in the rate of
      reinfarction (2.9% after rt-PA and 2.5% after PTCA). CONCLUSIONS: These findings
      suggest that in lytic-eligible patients not in shock, PTCA and rt-PA are
      comparable alternative methods of reperfusion when analyzed in terms of in
      hospital mortality, mortality plus nonfatal stroke and reinfarction.

PMID- 9581715
TI  - Time to therapy and salvage in myocardial infarction.
AB  - OBJECTIVES: This study sought to examine the influence of time to reperfusion on
      myocardial salvage. BACKGROUND: Major trials of reperfusion therapy for
      myocardial infarction (MI) have demonstrated improved outcome for patients
      achieving earlier reperfusion. However, some patients experience significant
      benefit despite delayed reperfusion. METHODS: Fifty-five patients with a first
      anterior MI underwent successful reperfusion therapy (angioplasty or
      thrombolysis). Technetium-99m (Tc-99m) sestamibi was injected before reperfusion
      therapy and again at hospital discharge to determine the myocardial salvage index
      for each patient. Residual flow to the infarct territory was assessed by the
      nadir of the Tc-99m sestamibi count-profile curve. RESULTS: The salvage index
      showed wide variability (range -0.04 to 1.0), and extreme values were seen in
      34.5% of the group (<0.10 in 9%, >0.90 in 25%). A high salvage index was
      associated with reperfusion therapy before 2 h (p=0.02) or good residual blood
      flow (p < 0.01). For the 10 patients who received reperfusion therapy within 2 h,
      residual blood flow was not correlated with salvage (p=0.12). For the 45 patients
      treated after 2 h, residual blood flow correlated significantly with salvage
      (r=0.57, p < 0.0001). There was a significant interaction (p < 0.05) between
      residual blood flow and time to therapy, indicating that the effect of each
      variable on salvage depended on the value of the other. Multiple historic and
      hemodynamic variables were examined, but none demonstrated any association with
      residual flow or myocardial salvage. CONCLUSIONS: In patients with acute MI,
      successful reperfusion therapy within 2 h is associated with the greatest degree
      of myocardial salvage. For patients treated after 2 h, residual blood flow to the
      infarct-related territory appears to be the most important determinant of
      myocardial salvage.

PMID- 9581716
TI  - Normal triglyceride levels and coronary artery disease events: the Baltimore
      Coronary Observational Long-Term Study.
AB  - OBJECTIVES: This study sought to evaluate long-term predictors of coronary events
      in men and women with arteriographically defined coronary artery disease (CAD).
      BACKGROUND: There is conflicting evidence of the role of triglycerides (TGs) as a
      prognosticator of CAD, and no studies have examined the long-term outcome of
      "normal" levels in predicting new coronary events. METHODS: This was a
      retrospective cohort study that evaluated 740 consecutive patients presenting for
      diagnostic coronary arteriography between 1977 and 1978. Beginning in 1988,
      patients with arteriographic CAD (n=350) were recontacted and asked to complete
      detailed medical questionnaires. Case and control patients were stratified by
      development of new coronary events, including death from ischemic heart disease,
      nonfatal myocardial infarction and revascularization. RESULTS: There were 199
      events during the 18-year follow-up period. The mean high density lipoprotein
      cholesterol (HDL-C) was significantly lower (35 vs. 39 mg/dl; p=0.002) and TGs
      higher (160 vs. 137 mg/dl; p=0.03) in case patients than in control patients;
      After adjusting for age, gender and beta-adrenergic blocking agent use, multiple
      logistic regression analysis revealed the following independent predictors of CAD
      events: diabetes mellitus (relative risk [RR] 2.1, 95% confidence interval [CI]
      1.4% to 3.1%), HDL-C <35 mg/dl (RR 1.5, 95% CI 1.1% to 2.00) and TGs >100 mg/dl
      (RR 1.5, 95% CI 1.1% to 2.1%). A Kaplan-Meier analysis revealed significantly
      reduced survival from CAD events in patients with baseline TG levels > or = 100
      mg/dl compared with TG levels <100 mg/dl (p=0.008). CONCLUSIONS: TG levels
      previously considered "normal" are predictive of new CAD events. The cutpoints
      established by the National Cholesterol Education Program for elevated TGs (>200
      mg/dl) may need to be refined.

PMID- 9581717
TI  - Plasma triglycerides and the clinician: time for reassessment.

PMID- 9581718
TI  - Elevated plasma lipoprotein(a) is associated with coronary artery disease in
      patients with chronic stable angina pectoris.
AB  - OBJECTIVES: We sought to assess the relation between plasma lipoprotein(a)
      [Lp(a)] levels, clinical variables and angiographic coronary artery disease (CAD)
      in patients with chronic stable angina. BACKGROUND: The relation between plasma
      Lp(a) levels and the severity and extent of angiographic CAD has not been studied
      in well characterized patients with stable angina pectoris. METHODS: We
      investigated clinical variables, lipid variables and angiographic scores in 129
      consecutive white patients (43 women) undergoing coronary angiography for chronic
      stable angina. RESULTS: Plasma Lp(a) levels were significantly higher in patients
      with than in those without significant angiographic stenoses (> or =70%) (372
      mg/liter [interquartile range 87 to 884] vs. 105 mg/liter [interquartile range 56
      to 366], respectively, p=0.002). This difference remained significant when
      patients with mild or severe angiographic disease were compared with those with
      completely normal coronary arteries (312 mg/liter [interquartile range 64 to 864]
      vs. 116 mg/liter [interquartile range 63 to 366], respectively, p=0.02). However,
      subset analysis indicated that this difference achieved statistical significance
      only in women. Multiple logistic regression analysis indicated that Lp(a)
      concentration was independently predictive of significant angiographic stenoses
      (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 2.0 to 42.1, p=0.006)
      and remained true even after exclusion of patients receiving lipid-lowering
      treatment (n=27) (OR 10.4, 95% CI 1.1 to 102.9, p=0.05). Lp(a) also had
      independent predictive value in a similar analysis using mild or severe
      angiographic disease as the outcome variable (OR 11.8, 95% CI 1.5 to 90.8,
      p=0.02). CONCLUSIONS: Our results indicate that elevated plasma Lp(a) is an
      independent risk factor for angiographic CAD in chronic stable angina and may
      have particular significance in women.

PMID- 9581719
TI  - Measuring the effect of risk factors on coronary atherosclerosis: coronary
      calcium score versus angiographic disease severity.
AB  - OBJECTIVES: This study sought to determine whether noninvasive quantification of
      coronary calcium is comparable to selective coronary angiography in measuring the
      effect of cardiovascular risk factors on coronary atherosclerosis. BACKGROUND:
      Electron beam computed tomography (EBCT) allows the delineation of anatomic
      coronary atherosclerotic disease and may be useful for noninvasively defining the
      role of established and new cardiovascular risk factors in selected patient
      groups. METHODS: A total of 211 consecutive patients, 26 to 79 years old,
      referred for evaluation of suspected or recently diagnosed coronary artery
      disease were examined. Selective coronary angiography was used to define five
      angiographic disease categories: normal coronary arteries, nonobstructive disease
      and one-, two- or three-vessel disease. EBCT was used to calculate coronary
      calcium scores, and cardiovascular risk, including lipid variables and fibrinogen
      levels, was assessed. RESULTS: Coronary calcium score and angiographic disease
      severity categories were largely predicted by identical risk factors (i.e., age,
      male gender, total/high density lipoprotein cholesterol ratio, fibrinogen) and,
      to a lesser degree, hypertension. Only smoking predicted angiographic disease
      severity but not calcium scores. The risk factors together explained a comparable
      proportion of the variability in angiographic disease categories and in calcium
      score quintiles (33% vs. 41%, p=0.16 by bootstrap analysis). An overall risk
      score composed of these risk factors separated angiographic disease categories
      and calcium score quintiles with a similar area under the receiver operating
      characteristic curve ([mean+/-SE] 0.81+/-0.03 vs. 0.83+/-0.03, p=NS).
      CONCLUSIONS: Quantification of coronary calcium is comparable to selective
      coronary angiography in measuring the effect of established cardiovascular risk
      factors on coronary atherosclerosis. Thus, EBCT may be useful for the noninvasive
      evaluation of the relations between conventional or developing cardiovascular
      risk factors and coronary atherosclerosis.

PMID- 9581720
TI  - Impact of coronary risk factors on contribution of nitric oxide and adenosine to
      metabolic coronary vasodilation in humans.
AB  - OBJECTIVES: The contribution of nitric oxide (NO) and adenosine to the increase
      in coronary blood flow (CBF) induced by cardiac pacing was investigated in 28
      subjects with angiographically normal coronary arteries with and without one or
      more risk factors for atherosclerosis. BACKGROUND: NO and adenosine are important
      in the regulation of coronary circulation, and the inhibition of NO synthesis
      increases adenosine production during cardiac pacing in experimental models.
      METHODS: Coronary artery diameters and CBF were assessed by quantitative coronary
      arteriography and Doppler flow velocity measurement. Plasma levels of nitrites
      and nitrates (NOx) (stable end products of NO), adenosine and lactate were
      measured, and blood gas analysis was performed. RESULTS: The extent of CBF
      response to cardiac pacing did not differ between the 14 subjects with and the 8
      subjects without risk factors for atherosclerosis. NOx (12.0+/-0.9 vs. 14.9+/-1.1
      ,amol/liter [mean+/-SD], p < 0.05), but not adenosine (50.8+/-7.2 vs. 50.8+/-6.5
      nmol/liter), levels in coronary sinus blood increased in the subjects without
      risk factors. In contrast, adenosine (58.9+/-7.5 vs. 77.4+/-9.8 nmol/liter, p <
      0.05), but not NOx (11.1+/-1.1 vs. 12.2+/-1.1 micromol/liter), levels increased
      in subjects with risk factors. Aminophylline, an antagonist of adenosine
      receptors, blunted CBF response to cardiac pacing in six subjects with risk
      factors. The number of risk factors showed a negative correlation (p < 0.05) with
      NOx production and a positive correlation (p < 0.05) with adenosine production
      during cardiac pacing, respectively. CONCLUSIONS: NO and adenosine are increased
      during metabolic coronary vasodilation induced by cardiac pacing. Adenosine
      production may be a compensatory mechanism when NO production is reduced.

PMID- 9581721
TI  - Thallium reinjection versus standard stress/delay redistribution imaging for
      prediction of cardiac events.
AB  - OBJECTIVES: The purpose of this study was to compare thallium reinjection with
      standard stress/delay redistribution for the prediction of cardiac events.
      BACKGROUND: Although thallium reinjection enhances the detection of viable
      myocardium, its contribution to prognosis over stress/delay redistribution in a
      general referral population has not been clearly evaluated. METHODS: This
      retrospective analysis included 366 consecutive patients with coronary artery
      disease who underwent stress/delay redistribution imaging and thallium
      reinjection scintigraphy, with a mean follow-up of 33+/-12 months. RESULTS:
      Cardiac events occurred in 48 patients (40 deaths, 8 myocardial infarctions). Of
      the 366 original patients, 159 demonstrated ischemia by stress/delay
      redistribution, 107 showed ischemia by reinjection only, and 100 showed
      infarction only. Cardiac events occurred in 20 patients (12.6%) with stress/delay
      redistribution, 13 patients (12%) with ischemia detected by thallium reinjection
      only and 15 patients (15%) with infarction only. The size of the reversible
      thallium defect by either stress/delay redistribution imaging or reinjection
      scintigraphy did not predict cardiac events. Independent predictors of cardiac
      events included left ventricular cavity size, the size of the abnormal perfusion
      defect and patient age. CONCLUSIONS: Thallium reinjection does not contribute
      independent prognostic utility for cardiac events when compared with stress/delay
      redistribution. Left ventricular dilation and the size of the post-stress defect
      were predictors of cardiac events.

PMID- 9581722
TI  - Assessing prognosis by means of radionuclide perfusion imaging: what technique
      and which variables should be used?

PMID- 9581724
TI  - Effect of high dose verapamil on restenosis after peripheral angioplasty.
AB  - OBJECTIVES: We sought to determine whether treatment with high dose verapamil
      prevents restenosis in patients at high risk for reoccurrence after successful
      percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Restenosis is
      the major limitation of PTCA. Calcium antagonists have demonstrated some
      potential as inhibitors of this process. METHODS: A total of 98 patients with
      peripheral occlusive arterial disease (POAD), stable angina pectoris, mild
      hypertension and at least one additional risk factor increasing the likelihood of
      restenosis after angioplasty were selected for this placebo-controlled, double
      blind, randomized trial. Verapamil (240 mg twice daily) or placebo was taken for
      6 months. Efficacy variables assessed before and after angioplasty and at 6 weeks
      and 6 months after PTCA included thickness of the intima/media complex degree of
      stenosis, interventricular septal thickness, crurobrachial pressure ratios of
      dorsalis pedis and posterior tibial arteries, distance to claudication and total
      vessel diameter. RESULTS: No significant intergroup differences emerged before or
      immediately after PTCA. Six weeks after angioplasty, a significant thickening of
      the intima/media complex in the treated vascular segment of 14.3% occurred in the
      placebo group versus 0% among verapamil patients (p < 0.01). At 6 months, the
      intima/media thickness was 35.7% greater in the placebo group but had decreased
      by 14.3% in the verapamil group (p < 0.001). At 6 months, a marked reduction in
      septal thickness was observed in the verapamil group versus that in the placebo
      group (p < 0.001). The rate of restenosis was also significantly lower in the
      verapamil group (p < 0.001). Few minor side effects were reported. CONCLUSIONS:
      In patients with POAD at increased risk for restenosis, the administration of
      high dose verapamil prevented recurrent stenosis for 6 months after successful
      peripheral angioplasty and was well tolerated.

PMID- 9581723
TI  - Predictors of restenosis after coronary stent implantation.
AB  - OBJECTIVES: We sought to determine predictors of restenosis after coronary
      stenting (CS) in a consecutive series of patients. BACKGROUND: Although stenting
      in highly selected patient groups reduces restenosis, the results of stenting in
      a heterogeneous patient group and the effects of clinical and procedural factors
      on stent restenosis are currently unclear. METHODS: We analyzed the 6-month
      angiographic outcome of 500 lesions in 463 consecutive patients undergoing
      successful CS. Clinical, qualitative and quantitative angiographic variables were
      correlated with restenosis assessed as both a binary and a continuous variable.
      RESULTS: Restenosis, defined as the presence of >50% diameter stenosis in the
      dilated segment, was present in 105 (26%) of the 405 lesions with angiographic
      follow-up. The mean late lumen loss during the follow-up period was 0.79+/-0.64
      mm. Implantation of multiple stents (p < 0.0001) and a high acute gain (p <
      0.0002) were independently associated with a higher late lumen loss. In contrast,
      the use of high inflation pressure (p < 0.02) and Palmaz-Schatz stents (p <
      0.005) was independently associated with a lower late lumen loss. When restenosis
      was defined as a qualitative variable, implantation of multiple stents (p <
      0.001), stenosis length (p < 0.01), small reference diameter (p < 0.02) and stent
      type other than Palmaz-Schatz (p < 0.01) were independent predictors of
      restenosis. None of the clinical variables tested was associated with restenosis.
      CONCLUSIONS: Coronary stenting in an unselected patient group is associated with
      an acceptable restenosis rate. Although some risk factors were identified, the
      risk of restenosis was not related to most of the variables tested. This suggests
      that the superiority of CS over balloon angioplasty, in terms of restenosis,
      might also apply to subgroups of patients that were not included in the recent
      randomized studies.

PMID- 9581725
TI  - Cost of cardiac care in the three years after coronary catheterization in a
      contained care system: critical determinants and implications.
AB  - OBJECTIVES: We sought to determine the clinical, angiographic, treatment and
      outcome correlates of the intermediate-term cost of caring for patients with
      suspected coronary artery disease (CAD). BACKGROUND: To adequately predict
      medical costs and to compare different treatment and cost reduction strategies,
      the determinants of cost must be understood. However, little is known about the
      correlates of costs of treatment of CAD in heterogeneous patient populations that
      typify clinical practice. METHODS: From a consecutive series of 781 patients
      undergoing cardiac catheterization in 1992 to 1994, we analyzed 44 variables as
      potential correlates of total (direct and indirect) in-hospital, 12- and 36-month
      cardiac costs. RESULTS: Mean (+/-SD) patient age was 65+/-10 years; 71% were men,
      and 45% had multiple vessel disease. The initial treatment strategy was medical
      therapy alone in 47% of patients, percutaneous intervention (PI) in 30% and
      coronary artery bypass graft surgery (CABG) in 24%. The 36-month survival and
      event-free (death, infarction, CABG, PI) survival rates were 89.6+/-0.2% and
      68.4+/-0.4%, respectively. Median hospital and 36-month costs were $8,301 and
      $28,054, respectively, but the interquartile ranges for both were wide and
      skewed. Models for log(e) costs were superior to those for actual costs. The
      variances accounted for by the all-inclusive models of in-hospital, 12- and 36
      month costs were 57%, 60% and 71%, respectively. Baseline cardiac variables
      accounted for 38% of the explained in-hospital costs, whereas in-hospital
      treatment and complication variables accounted for 53% of the actual costs.
      Noncardiac variables accounted for only 9% of the explained costs. Over time,
      complications (e.g., late hospital admission, PI, CABG) and drug use to prevent
      complications of heart transplantation became more important, but many baseline
      cardiac variables retained their importance. CONCLUSIONS: 1) Variables readily
      available from a comprehensive cardiovascular database explained 57% to 71% of
      cardiac costs from a hospital perspective over 3 years of care; 2) the initial
      revascularization strategy was a key determinant of in-hospital costs, but over 3
      years, the initial treatment become somewhat less important, and late
      complications became more important determinants of costs.

PMID- 9581726
TI  - Effects of mental stress on left ventricular and peripheral vascular performance
      in patients with coronary artery disease.
AB  - OBJECTIVES: We sought to investigate the mechanism of a mental stress-induced
      fall in left ventricular ejection fraction (LVEF) in patients with coronary
      artery disease. BACKGROUND: Mental stress induces a fall in LVEF in a significant
      proportion of patients with coronary artery disease. This is accompanied by an
      increase in heart rate, blood pressure and rate-pressure product. Whether the
      mental stress-induced fall in LVEF is due to myocardial ischemia, altered loading
      conditions or a combination of both is not clear. METHODS: Left ventricular (LV)
      function was studied noninvasively by serial equilibrium radionuclide
      angiocardiography and simultaneous measurement of peak power, a relatively
      afterload-independent index of LV contractility, in 21 patients with coronary
      artery disease (17 men, 4 women) and 9 normal subjects (6 men, 3 women) at
      baseline, during mental stress and during exercise. Peripheral vascular
      resistance (PVR), cardiac output (CO), arterial and end-systolic ventricular
      elastance (Ea, Ees,) and ventriculoarterial coupling (V/AC) were also calculated.
      Patients underwent two types of mental stress-mental arithmetic and anger recall
      as well as symptom-limited semisupine bicycle exercise. RESULTS: Nine patients
      (43%) had an absolute fall in LVEF of > or = 5% (Group I) in response to at least
      one of the mental stressors, whereas the remaining patients did not (Group II).
      Group I and Group II patients were similar in terms of baseline characteristics.
      Both groups showed a significant but comparable increase in systolic blood
      pressure (15+/-7 vs. 9+/-10 mm Hg, p=0.12) and a slight increase in heart rate
      (7+/-4 vs. 8+/-7 beats/min, p=0.6) and a comparable increase in rate-pressure
      product (2.2+/-0.9 vs. 1.9+/-1.2 beats/min x mm Hg, p=0.6) with mental stress.
      However, PVR increased in Group I and decreased in Group II (252+/-205 vs. -42+/
      230 dynes x s x cm(-5), p=0.006), and CO decreased in Group I and increased in
      Group II (-0.2+/-0.4 vs. 0.6+/-0.7 liters/min, p=0.02) with mental stress. There
      was no difference in the change in peak power (p=0.4) with mental stress. With
      exercise, an increase in systolic blood pressure, heart rate, rate-pressure
      product and CO and a fall in PVR were similar in both groups. Of the two mental
      stressors, anger recall resulted in a greater fall in LVEF and a greater increase
      in diastolic blood pressure. Exercise resulted in a fall in LVEF in 7 patients
      (33%). However, exercise-induced changes in LVEF and hemodynamic variables were
      not predictive of mental stress-induced changes in LVEF and hemodynamic
      variables. Conclusions. Abnormal PVR and Ea responses to mental stress and
      exercise are observed in patients with a mental stress-induced fall in LVEF.
      Peripheral vasoconstrictive responses to mental stress contribute significantly
      toward a mental stress-induced fall in LVEF.

PMID- 9581727
TI  - Randomized, double-blind, placebo-controlled study of the preventive effect of
      supplemental oral vitamin C on attenuation of development of nitrate tolerance.
AB  - OBJECTIVES: This study sought to evaluate the preventive effect of vitamin C, an
      antioxidant, on the development of nitrate tolerance. BACKGROUND: Decreased
      intracellular production of cyclic guanosine monophosphate (cGMP) is a mechanism
      of nitrate tolerance, and increased superoxide levels and reduced activation of
      guanylate cyclase have been observed in vitro. METHODS: In this double-blind,
      placebo-controlled study, 24 normal volunteers and 24 patients with ischemic
      heart disease (IHD) were randomized to receive either vitamin C (2 g three times
      daily [vitamin C group, n=12]) or placebo (placebo group, n=12). The vasodilator
      response to nitroglycerin was assessed with forearm plethysmography by measuring
      the change in FBF before and 5 min after sublingual administration of 0.3 mg of
      nitroglycerin. Blood samples were simultaneously obtained to measure platelet
      cGMP levels. FBF was measured, and blood sampling was performed serially at
      baseline (day 0), 3 days after administration of vitamin C or placebo (day 3) and
      3 days after application of a 10-mg/24-h nitroglycerin tape concomitantly with
      oral vitamin C or placebo (day 6). RESULTS: There were no differences between the
      vitamin C and placebo groups in percent increases in FBF (%FBF) or platelet cGMP
      levels (%cGMP) after administration of sublingual nitroglycerin on day O (%FBF:
      normal volunteers 31+/-8 vs. 32+/-10; patients with IHD 32+/-9 vs. 32+/-8; %cGMP:
      normal volunteers 37+/-9 vs. 39+/-10; patients with IHD 38+/-10 vs. 39+/-10
      [vitamin C group vs. placebo group]) or day 3 (%FBF: normal volunteers 32+/-9 vs.
      33+/-9; patients with IHD 31+/-10 vs. 31+/-10; %cGMP: normal volunteers 36+/-8
      vs. 37+/-9; patients with IHD 39+/-11 vs. 38+/-10 [vitamin C group vs. placebo
      group]). The %FBF and %cGMP in the placebo group were significantly lower on day
      6 than in the vitamin C group (%FBF: normal volunteers 30+/-8 vs. 19 4, p < 0.01;
      patients with IHD 29+/-9 vs. 17+/-6, p < 0.01; %cGMP: normal volunteers 36 10 vs.
      17+/-6, p < 0.01; patients with IHD 37+/-11 vs. 15+/-5, p < 0.01 [vitamin C group
      vs. placebo group]). CONCLUSIONS: These results indicate that combination therapy
      with vitamin C is potentially useful for preventing the development of nitrate
      tolerance.

PMID- 9581728
TI  - Effect of enalapril on endothelial function in young insulin-dependent diabetic
      patients: a randomized, double-blind study.
AB  - OBJECTIVES: We sought to determine whether 6 months of treatment with the
      angiotensin-converting enzyme (ACE) inhibitor enalapril can improve conduit
      artery endothelial function in young subjects with insulin-dependent diabetes
      mellitus (IDDM). BACKGROUND: Endothelial dysfunction is an early event in
      atherogenesis and has been demonstrated in young subjects with IDDM. ACE
      inhibitors have been shown to enhance conduit artery endothelial function in
      animal experiments and in patients with established coronary atherosclerosis,
      although their effect in IDDM is not known. METHODS: Ninety-one subjects (mean
      age 30.9 years, range 18 to 44) with stable IDDM but no clinical evidence of
      vascular disease were randomized to receive enalapril (20 mg once daily) (46
      subjects) or placebo (45 subjects) in a randomized, double-blind, parallel-group
      study. Brachial artery flow-mediated dilation (FMD), an endothelium-dependent
      stimulus, and response to glyceryl trinitrate (GTN), which acts directly on
      vascular smooth muscle, were assessed noninvasively by means of high resolution
      external vascular ultrasound at baseline and after 12 and 24 weeks of treatment.
      RESULTS: FMD was inversely correlated with total cholesterol (r=0.22, p=0.041)
      but not with any diabetic variables. Treatment with enalapril had no significant
      effect on FMD (p=0.67) or response to the endothelial-independent dilator GTN
      (p=0.45). CONCLUSIONS: These data suggest that impairment of endothelial
      dependent dilation in young subjects with IDDM is not improved by treatment with
      the ACE inhibitor enalapril. This lack of improvement may reflect the complex
      nature of vascular disease in IDDM, which can affect both endothelial and smooth
      muscle function.

PMID- 9581729
TI  - Combined oral positive inotropic and beta-blocker therapy for treatment of
      refractory class IV heart failure.
AB  - OBJECTIVES: We sought to assess the effects of combined oral positive inotropic
      and beta-blocker therapy in patients with severe heart failure. BACKGROUND:
      Patients with severe, class IV heart failure who receive standard medical therapy
      exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not
      tolerate beta-blockade, a promising new therapy for chronic heart failure.
      Positive inotropes, including phosphodiesterase inhibitors, are associated with
      increased mortality when administered over the long term in these patients. The
      addition of a beta-blocker to positive inotropic therapy might attenuate this
      adverse effect, although long-term oral inotropic therapy might serve as a bridge
      to beta-blockade. METHODS: Thirty patients with severe heart failure (left
      ventricular ejection fraction [LVEF] 17.2+/-1.2%, cardiac index 1.6+/-0.1
      liter/min per m2) were treated with the combination of oral enoximone (a
      phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone
      was given at a dose of < or = 1 mg/kg body weight three times a day. After
      clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and
      slowly titrated up to a target dose of 100 to 200 mg/day. RESULTS: Ninety-six
      percent of the patients tolerated enoximone, whereas 80% tolerated the addition
      of metoprolol. The mean duration of combination therapy was 9.4+/-1.8 months. The
      mean length of follow-up was 20.9+/-3.9 months. Of the 23 patients receiving the
      combination therapy, 48% were weaned off enoximone over the long term. The LVEF
      increased significantly, from 17.7+/-1.6% to 27.6+/-3.4% (p=0.01), whereas the
      New York Heart Association functional class improved from 4+/-0 to 2.8+/-0.1
      (p=0.0001). The number of hospital admissions tended to decrease during therapy
      (p=0.06). The estimated probability of survival at 1 year was 81+/-9%. Heart
      transplantation was performed successfully in nine patients (30%). CONCLUSIONS:
      Combination therapy with a positive inotrope and a beta-blocker appears to be
      useful in the treatment of severe, class IV heart failure. It may be used as a
      palliative measure when transplantation is not an option or as a bridge to heart
      transplantation. Further study of this form of combined therapy is warranted.

PMID- 9581730
TI  - Phosphodiesterase inhibitors in refractory heart failure: bridge to beta
      blockade?

PMID- 9581732
TI  - Increased oxidative stress in patients with congestive heart failure.
AB  - OBJECTIVES: We sought to study the markers of lipid peroxidation and defenses
      against oxidative stress in patients with varying degrees of heart failure.
      BACKGROUND: Despite advances in other areas of cardiovascular disease, the
      morbidity and mortality from congestive heart failure (CHF) are increasing. Data
      mainly from animal models suggest that free radical injury may promote myocardial
      decompensation. However, there are no studies in humans correlating the severity
      of heart failure with increased free radical injury and antioxidants. METHODS:
      Fifty-eight patients with CHF and 19 control subjects were studied. In addition
      to complete clinical and echocardiographic evaluations, the prognosis of these
      patients was established by measuring the levels of soluble tumor necrosis factor
      alpha receptors 1 and 2 (sTNF-R1 and sTNF-R2). Oxidative stress was evaluated by
      measuring plasma lipid peroxides (LPO), malondialdehyde (MDA), glutathione
      peroxidase (GSHPx) and vitamin E and C levels. RESULTS: The patients' age range,
      cause of heart failure and drug intake were comparable across the different
      classes of heart failure. Heart failure resulted in a significant increase in LPO
      (p < 0.005), MDA (p < 0.005), sTNF-R1 (p < 0.005) and sTNF-R2 (p < 0.005). There
      was a significant positive correlation between the clinical class of heart
      failure and LPO, MDA, sTNF-R1 and sTNF-R2 levels. There was an inverse
      correlation between GSHPx and LPO. With increased lipid peroxidation in patients
      with CHF, the levels of vitamin C decreased, but vitamin E levels were
      maintained. CONCLUSIONS: These data demonstrate a progressive increase in free
      radical injury and encroachment on antioxidant reserves with the evolution of
      heart failure; they also suggest that oxidative stress may be an important
      determinant of prognosis. The therapeutic benefit of administering antioxidant
      supplements to patients with CHF should be evaluated.

PMID- 9581731
TI  - Direct myocardial effects of OPC-18790 in human heart failure: beneficial effects
      on contractile and diastolic function demonstrated by intracoronary infusion with
      pressure-volume analysis.
AB  - OBJECTIVES: We sought to determine the precise myocardial effects of OPC-18790 as
      demonstrated by intracoronary administration. BACKGROUND: Although previous
      studies have determined the cardiovascular effects of a novel intravenous
      inotrope, OPC-18790, the observed benefits on contractile and diastolic function
      may have been confounded by the marked changes in peripheral loading associated
      with this drug when given intravenously. METHODS: Eight heart failure patients
      received intracoronary OPC-18790 at 31.25 microg/min for 20 min, and then at 62.5
      microg/min for another 20 min. Hemodynamic variables and pressure-volume indexes
      using the conductance catheter method were determined at baseline and then after
      the two doses. RESULTS: There were no significant effects on heart rate, cardiac
      output or loading conditions, including afterload as determined by systemic
      vascular resistance and arterial elastance (Ea) and preload as determined by end
      diastolic volume (EDV). There were significant increases in end-systolic
      elastance (Ees) from 0.74+/-0.11 to 0.90+/-0.16 mm Hg/ml at 31.25 microg/min and
      to 137+/-0.33 mm Hg/ml at 62.5 microg/min (p < 0.05 by analysis of variance
      [ANOVA]). Diastolic function improved, as determined by the time constant for
      isovolumetric relaxation tau, which decreased significantly from baseline to
      31.25 microg/min (94+/-9 to 79+/-9 ms, p < 0.05), and did not shorten further at
      62.5 microg/min (78+/-8 ms, p=NS). There were significant decreases in right
      atrial pressure (9+/-1 to 7+/-1 mm Hg, p < 0.01 by ANOVA) and mean pulmonary
      artery wedge pressure (21+/-3 to 16+/-2 mm Hg, p < 0.05 by ANOVA). This fall in
      filling pressures was not accompanied by any change in EDV. Inspection of the
      diastolic portion of the pressure-volume curve confirmed a downward shift
      consistent with pericardial release in five of the eight patients. CONCLUSIONS:
      Intracoronary administration of OPC-18790 demonstrates that the direct myocardial
      effects of this agent include a modest increase in inotropy and improvement in
      diastolic function, both of which occur without increases in heart rate,
      indicating that this agent may be beneficial for the intravenous treatment of
      congestive heart failure.

PMID- 9581733
TI  - Evaluation of biopsy classification for rejection: relation to detection of
      myocardial damage by monoclonal antimyosin antibody imaging.
AB  - OBJECTIVES: This study sought to compare the histologic grades of rejection in
      endomyocardial biopsy specimens with the global estimate of myocardial transplant
      related cardiac damage detected by myocardial uptake of monoclonal antimyosin
      antibodies. BACKGROUND: The diagnosis and treatment of acute cardiac allograft
      rejection is based on the interpretation of endomyocardial biopsies. Because
      allograft rejection is a multifocal process and biopsy is obtained from a small
      area of the right ventricle, sampling error may occur. Global assessment of
      myocardial damage associated with graft rejection is now possible with the use of
      antimyosin scintigraphy. The present study was undertaken to compare the
      histologic grades of rejection in endomyocardial biopsy specimens with the global
      assessment of transplant-related myocardial damage detected by antimyosin
      scintigraphy. METHODS: Biopsies (n=395) from 112 patients were independently
      interpreted by three pathologists in a blinded manner according to the original
      Stanford four-grade (normal, mild, moderate and severe) and the current
      International Society of Heart and Lung Transplantation (ISHLT) seven-grade (0,
      1A, 1B, 2, 3A, 3B and 4) classifications. The results were correlated with 395
      antimyosin studies performed at the time of the biopsies. The heart/lung ratio of
      antimyosin antibody uptake was used to assess the severity of myocardial damage.
      RESULTS: In the Stanford biopsy grade classification, significantly higher
      antimyosin uptake, indicating increasing degrees of myocardial damage, were
      associated with normal (1.78+/-0.26), mild (1.88+/-0.31) and moderate (1.95+/
      0.38) biopsy classifications for rejection (p < 0.01). In the ISHLT
      classification, significant differences were detected only for antimyosin uptake
      associated with grades 0 (1.77+/-0.26) and 3A (1.98+/-0.39) but not for
      intermediate scores (1A, 1B and 2). In view of the similar intensity of antibody
      uptake among the various grades, ISHLT biopsy scores were regrouped: normal
      biopsies in grade A; 1A and 1B as grade B; and 2 and 3A as grade C. Antimyosin
      uptake in grades A, B and C was 1.78+/-0.26, 1.88+/-0.31, 1.95+/-0.38,
      respectively (p < 0.01). CONCLUSIONS: The current ISHLT seven-grade scoring
      system does not reflect the progressive severity of myocardial damage associated
      with heart transplant rejection. Because myocardial damage constitutes the basis
      of treatment for allograft rejection, there is a need to reevaluate the ISHLT
      grading system, given its importance for multicenter trials.

PMID- 9581734
TI  - Handgrip increases endothelin-1 secretion in normotensive young male offspring of
      hypertensive parents.
AB  - OBJECTIVES: We tested the hypothesis that an abnormal response of plasma
      endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive
      offspring of hypertensive parents. BACKGROUND: It has been hypothesized that ET-1
      is involved in blood pressure control and plays a pathophysiologic role in the
      development of clinical hypertension. METHODS: Two groups of healthy male
      subjects, 11 with hypertensive parents (group A) and 10 without a family history
      of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart
      rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine
      were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of
      recovery. RESULTS: Group A had higher norepinephrine levels than group B
      throughout the test (baseline 181+/-32 [SEM] vs. 96+/-12 pg/ml, p < 0.05; peak HG
      467+/-45 vs. 158+/-12 pg/ml, p < 0.000001; R2 293+/-46 vs. 134+/-8 pg/ml, p <
      0.01; RO1 214+/-27 vs. 129+/-10 pg/ml, p < 0.0005); no significant difference in
      epinephrine levels was detected. Compared with group B subjects, group A had
      higher baseline ET-1 levels (1.07+/-0.14 vs. 0.59+/-0.11 pg/ml, p < 0.02), which
      increased to a greater extent at peak HG (1.88+/-0.31 vs. 0.76+/-0.09 pg/ml, p <
      0.005) and R2 (2.46+/-0.57 vs. 1.31+/-0.23 pg/ml, p < 0.05) and remained elevated
      at R10 (3.16+/-0.78 vs. 0.52+/-0.09 pg/ml, p < 0.002). Multivariate analysis
      demonstrated that only a family history of hypertension (chi-square=7.59,
      p=0.0059) and ET-1 changes during HG (chi-square=4.23, p=0.0398) were predictive
      of blood pressure response to HG and that epinephrine and norepinephrine were
      not. CONCLUSIONS: The response to HG in offspring of hypertensive parents
      produced increased ET-1 plasma levels and resulted in a sustained ET-1 release
      into the bloodstream during recovery compared with offspring of normotensive
      parents. This may be an important marker for future clinical hypertension.

PMID- 9581735
TI  - Noninvasive differential diagnosis between chronic pulmonary thromboembolism and
      primary pulmonary hypertension by means of Doppler ultrasound measurement.
AB  - OBJECTIVES: The purpose of this investigation was to differentiate chronic
      pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by
      using noninvasive Doppler ultrasound techniques. BACKGROUND: A recent
      investigation in our laboratory has indicated that the pulmonary artery (PA)
      pressure waveform conveys significant information that can be used to
      differentiate CPTE from PPH. Pulse pressure was markedly larger in CPTE than in
      PPH, indicating that the major occlusive site is central in CPTE and peripheral
      in PPH. METHODS: In 19 patients with CPTE and 16 patients with PPH, we estimated
      PA systolic pressure and diastolic pressure from the velocities of tricuspid
      regurgitation and pulmonary regurgitation, respectively. RESULTS: Estimated
      systolic pressure was not significantly different between CPTE and PPH (mean [+/
      SD] 81+/-20 and 79+/-21 mm Hg, respectively, p=NS). Pulse pressure normalized by
      systolic pressure was higher in CPTE than in PPH (0.82+/-0.05 vs. 0.63+/-0.10,
      respectively, p < 0.01). Pulse pressure normalized by mean pressure was also
      higher in CPTE than in PPH (1.65+/-0.30 vs. 0.94+/-0.25, respectively, p < 0.01).
      Receiver operating characteristic analysis indicated that pulse pressure
      normalized by systolic pressure separated CPTE from PPH, with a sensitivity of
      0.95 and a specificity of 1.00. Pulse pressure normalized by mean pressure also
      separated them, with a sensitivity of 0.95 and a specificity of 1.00.
      CONCLUSIONS: Normalized pulse pressures estimated from Doppler ultrasound
      measurements enable us to noninvasively differentiate between CPTE and PPH.

PMID- 9581736
TI  - Partitioning of pulmonary vascular resistance in primary pulmonary hypertension.
AB  - OBJECTIVES: This study sought to determine the site of increased pulmonary
      vascular resistance (PVR) in primary pulmonary hypertension by standard bedside
      hemodynamic evaluation. BACKGROUND: The measurement of pulmonary vascular
      pressures at several levels of flow (Q) allows the discrimination between active
      and passive, flow-dependent changes in mean pulmonary artery pressure (Ppa), and
      may detect the presence of an increased pulmonary vascular closing pressure. The
      determination of a capillary pressure (Pc') from the analysis of a Ppa decay
      curve after balloon occlusion allows the partitioning of PVR in an arterial and a
      (capillary + venous) segment. These approaches have not been reported in primary
      pulmonary hypertension. METHODS: Ppa and Pc' were measured at baseline and after
      an increase in Q induced either by exercise or by an infusion of dobutamine, at a
      dosage up to 8 microg/kg body weight per min, in 11 patients with primary
      pulmonary hypertension. Reversibility of pulmonary hypertension was assessed by
      the inhalation of 20 ppm nitric oxide (NO), and, in 6 patients, by an infusion of
      prostacyclin. RESULTS: At baseline, Ppa was 52+/-3 mm Hg (mean value+/-SE), Q
      2.2+/-0.2 liters/min per m2, and Pc' 29+/-3 mm Hg. Dobutamine did not affect Pc'
      and allowed the calculation of an averaged extrapolated pressure intercept of
      Ppa/Q plots of 34 mm Hg. Inhaled NO had no effect. Prostacyclin decreased Pc' and
      PVR. Exercise increased Pc' to 40+/-3 mm Hg but did not affect PVR. CONCLUSIONS:
      ns. These findings are compatible with a major increase of resistance and
      reactivity at the periphery of the pulmonary arterial tree.

PMID- 9581737
TI  - Reduced cardiopulmonary baroreflex sensitivity in patients with hypertrophic
      cardiomyopathy.
AB  - OBJECTIVES: We sought to assess baroreflex function in patients with hypertrophic
      cardiomyopathy (HCM). BACKGROUND: We have previously demonstrated a specific
      abnormality in the afferent limb of the cardiopulmonary baroreflex in patients
      with vasovagal syncope. Patients with HCM exhibit abnormal control of their
      vasculature during exercise and upright tilt; we therefore hypothesize a similar
      abnormality in the afferent limb of the cardiopulmonary baroreflex arc. METHODS:
      We investigated 29 patients with HCM and 32 control subjects. Integrated
      baroreceptor sensitivity was assessed after administration of phenylephrine.
      Cardiopulmonary baroreceptor sensitivity was assessed by measuring forearm
      vascular resistance (FVR) during lower body negative pressure (LBNP). Carotid
      artery baroreflex sensitivity was assessed by measuring the in RR interval during
      manipulation of carotid artery transmural pressure. The integrity of the efferent
      limb of the reflex arc was determined by studying responses to both handgrip and
      peripheral alpha-receptor sensitivity. RESULTS: During LBNP, FVR increased by
      only 2.36+/-9 U in patients, compared with an increase of 123+/-8.76 U in control
      subjects (p=0.001). FVR paradoxically fell in eight patients, but in none of the
      control subjects. Furthermore, FVR fell by 4.9+/-5.6 U in patients with a history
      of syncope, compared with an increase of 4.7+/-7.2 U in those without syncope
      (p=0.014). Integrated and carotid artery baroreflex sensitivities were similar in
      patients and control subjects (14+/-7 vs. 14+/-6 ms/mm Hg, p=NS and -3+/-2 vs. 
      4+/-2 ms/mm Hg, p=NS, respectively). Similarly, handgrip responses and the
      dose/response ratio to phenylephrine were not significantly different.
      CONCLUSIONS: This study suggests that patients with HCM have a defect in the
      afferent limb of the cardiopulmonary reflex arc.

PMID- 9581738
TI  - Quantitation of mitral regurgitation using the systolic/diastolic pulmonary
      venous flow velocity ratio.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that pulmonary
      venous flow velocity ratios during systole and diastole in patients with mitral
      regurgitation (MR) correctly predict the quantitative degree of MR. BACKGROUND:
      Pulmonary venous flow velocity measurements have thus far been used only for the
      qualitative assessment of MR. Recent studies have evaluated this method using
      transesophageal echocardiography against semiquantitative references. METHODS: In
      100 patients without aortic regurgitation or atrial fibrillation and with left
      ventricular (LV) ejection fraction >45%, MR was assessed by quantitative
      echocardiographic Doppler and color Doppler, providing forward and total LV
      stroke volume for the calculation of the mitral regurgitant fraction
      (RFstandard), the reference parameter, and also supplying mitral regurgitant
      orifice area (ROA) values and the RF by the flow convergence method (RFPISA
      [proximal isovelocity surface area]). Measurements of pulmonary venous flow
      velocity time integral values during systole to diastole (VTIs/VTId) were
      obtained and tested for their predictibility of ROA, RFstandard and RFPISA.
      RESULTS: There was an inverse and significant correlation between VTIs/VTId and
      ROA, RFPISA and RFstandard, respectively: RFstandard=49 - 20 VTIs/VTId, r=0.77,
      p=0.0001. A principal source of variability in the relation between VTIs/VTId and
      RFstandard was the presence of mitral valve prolapse as the cause of MR.
      Pulmonary venous flow reversal (VTIs/VTId <0) correctly identified severe MR with
      52% sensitivity, 96% specificity and 80% positive and 87% negative predictive
      accuracy. CONCLUSIONS: The VTIs/VTId ratio allows a moderately accurate
      assessment of the severity of MR.

PMID- 9581739
TI  - Comparison of single- and dual-coil active pectoral defibrillation lead systems.
AB  - OBJECTIVES: The purpose of this study was to compare defibrillation thresholds
      with lead systems consisting of an active left pectoral electrode and either
      single or dual transvenous coils. BACKGROUND: Lead systems that include an active
      pectoral pulse generator reduce defibrillation thresholds and permit transvenous
      defibrillation in nearly all patients. A further improvement in defibrillation
      efficacy is desirable to allow for smaller pulse generators with a reduced
      maximal output. METHODS: This prospective study was performed in 50 consecutive
      patients. Each patient was evaluated with two lead configurations with the order
      of testing randomized. Shocks were delivered between the right ventricular coil
      and either an active can alone (single coil) or an active can with the proximal
      atrial coil (dual coil). The right ventricular coil was the cathode for the first
      phase of the biphasic defibrillation waveform. RESULTS: Delivered energy at the
      defibrillation threshold was 10.1+/-5.0 J for the single-coil configuration and
      8.7+/-4.0 J for the dual-coil configuration (p < 0.02). Moreover, 98% of patients
      had low (<15 J) thresholds with the dual-coil lead system, compared with 88% of
      patients with the single-coil configuration (p=0.05). Leading edge voltage (p <
      0.001) and shock impedance (p < 0.001) were also decreased with the dual-coil
      configuration, although peak current was increased (p < 0.001). CONCLUSIONS: A
      dual-coil, active pectoral lead system reduces defibrillation energy requirements
      compared with a single-coil, unipolar configuration.

PMID- 9581740
TI  - Effect of direct current shocks on left atrial mechanical function in patients
      with structural heart disease.
AB  - OBJECTIVES: This study examined the effect of endocardial and transthoracic
      direct current (DC) shocks on left atrial and left atrial appendage function in
      humans with structural heart disease. BACKGROUND: DC cardioversion of atrial
      fibrillation (AF) to sinus rhythm is associated with transient left atrial and
      left atrial appendage dysfunction and the development of spontaneous echo
      contrast (SEC). This phenomenon has been termed atrial "stunning" and may be
      associated with thrombus formation and embolic stroke. To what extent the shock
      itself contributes to atrial stunning is unclear. METHODS: Thirteen patients in
      sinus rhythm undergoing implantation of a ventricular implantable cardioverter
      defibrillator (ICD) were prospectively evaluated. All patients had significant
      structural heart disease. To evaluate the effects of DC shocks on left atrial and
      left atrial appendage function, biphasic R wave synchronized endocardial shocks
      of 1, 10 and 20 J were delivered between the right ventricular electrode and the
      left pectoral generator of the ICD in sinus rhythm. R wave synchronized
      transthoracic shocks of 360 J were also delivered between anteriorly and
      posteriorly positioned chest electrodes. Transesophageal echocardiography was
      performed to evaluate left atrial appendage velocities, mitral inflow velocities
      and the presence of SEC before and immediately after each DC shock. RESULTS:
      There were no significant changes in left atrial or left atrial appendage
      function after endocardial or transthoracic DC shocks. Left atrial SEC did not
      develop after endocardial or transthoracic DC shocks. CONCLUSIONS: Endocardial
      and transthoracic DC shocks are not directly responsible for left atrial and left
      atrial appendage stunning and do not contribute to the stunning that is observed
      after the cardioversion of AF to sinus rhythm.

PMID- 9581741
TI  - Effects of epinephrine and phenylephrine on QT interval dispersion in congenital
      long QT syndrome.
AB  - OBJECTIVES: Measurement of QT interval dispersion during pharmacologic adrenergic
      stimulation was used to assess the effect of alpha- and beta-adrenergic
      stimulation on arrhythmic vulnerability in familial long QT syndrome (LQTS).
      BACKGROUND: Nonhomogeneity in the ventricular action potential duration causes
      electrical instability leading to life-threatening ventricular arrhythmias and is
      markedly increased in LQTS. QT interval dispersion measured from the
      electrocardiogram (ECG) can be used as an index of nonhomogeneous ventricular
      repolarization. METHODS: Sixteen symptomatic patients with LQTS and nine healthy
      control subjects were examined at baseline and during epinephrine (mainly beta
      adrenergic agonist, 0.05 microg/kg body weight per min) and phenylephrine
      infusions (alpha-adrenergic agonist, mean 1.4 microg/kg per min). QT interval
      dispersion was determined from a 12-lead ECG as interlead range and coefficient
      of variation measured to the end (QTend) and apex (QTapex) of the T wave.
      RESULTS: At baseline QTend dispersion was greater in patients with LQTS compared
      with control subjects (mean [+/-SD] 68+/-34 vs. 36+/-7 ms, p=0.001). QTend
      dispersion was markedly increased in patients with LQTS by use of epinephrine
      (from 68+/-34 to 90+/-36 ms, p=0.002), but remained unchanged in control
      subjects. Phenylephrine did not affect QT dispersion in either group (all p=NS).
      Atrial pacing to achieve comparable heart rates during baseline and epinephrine
      and phenylephrine infusions did not influence the magnitude of QT dispersion in
      either group. QTapex dispersion analysis gave congruent results. CONCLUSIONS:
      Epinephrine but not phenylephrine increased QT dispersion, suggesting that beta
      adrenergic stimulation provokes arrhythmias in patients with LQTS by aggravating
      nonhomogeneity of ventricular repolarization, whereas alpha-adrenergic
      stimulation is less important for arrhythmic vulnerability. The results also
      suggest that rapid pacing may not reduce vulnerability to arrhythmias in
      congenital LQTS.

PMID- 9581742
TI  - Electrocardiographic identification of abnormal ventricular depolarization and
      repolarization in patients with idiopathic ventricular fibrillation.
AB  - OBJECTIVES: We sought to gain more insight into the arrhythmogenic etiology of
      idiopathic ventricular fibrillation (VF) by assessing ventricular depolarization
      and repolarization properties by means of various electrocardiographic (ECG)
      techniques. BACKGROUND: Idiopathic VF occurs in the absence of demonstrable
      structural heart disease. Abnormalities in ventricular depolarization or
      repolarization have been related to increased vulnerability to VF in various
      cardiac disorders and are possibly also present in patients with idiopathic VF.
      METHODS: In 17 patients with a first episode of idiopathic VF, 62-lead body
      surface QRST integral maps, QT dispersion on the 12-lead ECG and XYZ-lead signal
      averaged ECGs were computed. RESULTS: All subjects of a healthy control group had
      a normal dipolar QRST integral map. In patients with idiopathic VF, either a
      normal dipolar map (29%,), a dipolar map with an abnormally large negative area
      on the right side of the thorax (24%) or a nondipolar map (47%) were recorded.
      Only four patients (24%) had increased QT dispersion on the 12-lead ECG and late
      potentials could be recorded in 6 (38%) of 16 patients. During a median follow-up
      duration of 56 months (range 9 to 136), a recurrent arrhythmic event occurred in
      7 patients (41%), all of whom had an abnormal QRST integral map. Five of these
      patients had late potentials, and three showed increased QT dispersion on the 12
      lead ECG. CONCLUSIONS: In patients with idiopathic VF, ventricular areas of slow
      conduction, regionally delayed repolarization or dispersion in repolarization can
      be identified. Therefore, various electrophysiologic conditions, alone or in
      combination, may be responsible for the occurrence of idiopathic VF. Body surface
      QRST integral mapping may be a promising method to identify those patients who do
      not show a recurrent episode of VF.

PMID- 9581743
TI  - Conversion efficacy and safety of intravenous ibutilide compared with intravenous
      procainamide in patients with atrial flutter or fibrillation.
AB  - OBJECTIVES: This multicenter study compared the efficacy and safety of ibutilide
      versus procainamide for conversion of recent-onset atrial flutter or
      fibrillation. BACKGROUND: Ibutilide fumarate is an intravenous (IV) class III
      antiarrhythmic agent that has been shown to be significantly more effective than
      placebo in the pharmacologic conversion of atrial flutter and fibrillation to
      sinus rhythm. Procainamide is commonly used for conversion of recent-onset atrial
      fibrillation to normal sinus rhythm. METHODS: One hundred twenty-seven patients
      (age range 22 to 92 years) with atrial flutter or fibrillation of 3 h to 90 days'
      (mean 21 days) duration were randomized to receive either two 10-min IV infusions
      of 1 mg of ibutilide fumarate, separated by a 10-min infusion of 5% dextrose in
      sterile water, or three successive 10-min IV infusions of 400 mg of procainamide
      hydrochloride. RESULTS: Of the 127 patients, 120 were evaluated for efficacy: 35
      (58.3%) of 60 in the ibutilide group compared with 11 (18.3%) of 60 in the
      procainamide group had successful termination within 1.5 h of treatment (p <
      0.0001). Seven patients were found to have violated the protocol and were not
      included in the final evaluation. In the patients with atrial flutter, ibutilide
      had a significantly higher success rate than procainamide (76% [13 of 17] vs. 14%
      [3 of 22], p=0.001). Similarly, in the atrial fibrillation group, ibutilide had a
      significantly higher success rate than procainamide (51% [22 of 43] vs. 21% [8 of
      38], p=0.005). One patient who received ibutilide, which was found to be a
      protocol violation, had sustained polymorphic ventricular tachycardia requiring
      direct current cardioversion. Seven patients who received procainamide became
      hypotensive. CONCLUSIONS: This study establishes the superior efficacy of
      ibutilide over procainamide when administered to patients to convert either
      atrial fibrillation or atrial flutter to sinus rhythm. Hypotension was the major
      adverse effect seen with procainamide. A low incidence of serious proarrhythmia
      was seen with the administration of ibutilide occurring at the end of infusion.

PMID- 9581744
TI  - Clinical anatomy of the normal pulmonary root compared with that in isolated
      pulmonary valvular stenosis.
AB  - OBJECTIVES: This study aimed to clarify the clinical anatomy of the pulmonary
      root. BACKGROUND: Many descriptions of valvular anatomy have focused on the
      annulus, leading to varied interpretations of abnormal valves. METHODS: Twenty
      two heart specimens with isolated pulmonary valvular stenosis were examined to
      analyze the gross structure of the pulmonary root. For comparison, we examined a
      normal series of a similar age range together with nine adult hearts. Serial
      histologic sections were prepared from five specimens. RESULTS: The normal
      pulmonary valve is enclosed in a proximal sleeve of free-standing right
      ventricular infundibulum supporting the fibroelastic walls of the pulmonary
      sinuses at the anatomic ventriculoarterial junction. The valvular leaflets are
      attached in semilunar fashion across this junction, delimiting the extent of the
      valvular sinuses. The stenotic valves were separated into dome-shaped valves,
      dysplastic valves and a third group of less typical cases. In the dome-shaped
      valves, which had a relatively circular origin of their leaflets, three raphes
      were tethered to the arterial wall at the sinutubular junction, producing a
      waistlike narrowing. The leaflets of the dysplastic valves were attached in a
      relatively normal semilunar fashion, but stenosis was caused by thickening of the
      leaflets at their free edges. Serial histologic sections through normal and
      abnormal valves failed to demonstrate any well defined fibrous "annulus" that
      could be of clinical relevance. CONCLUSIONS: Unlike the normal and the dysplastic
      valves, the dome-shaped valves have circular rather than semilunar lines of
      attachment of the valvular leaflets. Liberation of the fused zones of apposition
      of the leaflets within the dome is unlikely to restore such abnormal valves to
      normal structure, even if this procedure relieves the stenosis.

PMID- 9581745
TI  - Angiogenesis is enhanced in ischemic canine myocardium by transmyocardial laser
      revascularization.
AB  - OBJECTIVES: This study sought to test whether transmyocardial laser
      revascularization (TMLR) stimulates angiogenesis in an animal model of chronic
      ischemia. BACKGROUND: TMLR relieves angina and may also improve blood flow in
      patients who are not candidates for traditional therapies. The mechanisms of
      these benefits are not fully defined. METHODS: Ischemia was created in 14 dogs by
      proximal left anterior descending coronary ameroid constrictors. TMLR was
      performed in the anterior wall (approximately 1 channel/cm2) of seven dogs; the
      remaining dogs served as the ischemic control group. Myocardial blood flow was
      measured (colored microspheres) at rest and during chemical stress (adenosine) in
      the acute setting and after 2 months. RESULTS: TMLR did not influence blood flow
      in the acute setting. After 2 months, resting blood flow increased comparably in
      the anterior wall in both groups to approximately 80% of normal. However, the
      TMLR-treated dogs demonstrated an approximately 40% increase in blood flow
      capacity during stress in the ischemic territory compared with untreated dogs
      (left anterior descending coronary artery/left circumflex coronary artery flow
      0.53+/-0.16 in the control group vs. 0.73+/-0.08 in TMLR animals, p < 0.05).
      Vascular proliferation, assessed by bromodeoxyuridine incorporation and
      proliferating cell nuclear antigen positivity in endothelial and smooth muscle
      cells was about four times greater in the TMLR group than in the control group (p
      < 0.001). The density of vessels with at least one smooth muscle cell layer was
      approximately 1.4 times greater in the myocardium surrounding the TMLR channel
      remnants than in control ischemic tissue (p < 0.001). CONCLUSIONS: In this canine
      model of chronic ischemia, TMLR significantly enhances angiogenesis as evidenced
      by the increased number of vessels lined with smooth muscle cells, markedly
      increased vascular proliferation and increased blood flow capacity during stress.

PMID- 9581746
TI  - Fibrin-film stenting in a porcine coronary injury model: efficacy and safety
      compared with uncoated stents.
AB  - OBJECTIVES: This study was designed to test the efficacy and safety of a fibrin
      film-covered stent compared with that of a bare metal stent in the porcine
      coronary injury model. BACKGROUND: Biodegradable stents are a potential method of
      achieving total lesion coverage and delivering local, lesion-specific drug
      therapy. METHODS: Two coronary arteries in each pig were randomly assigned to
      deployment of either a fibrin-film or a bare tantalum wire-coil stent. An
      oversized balloon injury, 1.15 to 1.30 times the reference vessel diameter, was
      induced in each coronary segment before stenting to simulate angioplasty injury.
      Thirty pigs were studied: group 1 for 28 days (15 pigs); group 2 for 90 days (5
      pigs); group 3 for 6 months (5 pigs); group 4 for 1 year (5 pigs). RESULTS: Two
      pigs died of occlusion of the bare stent and one of occlusion of the fibrin stent
      (p > 0.99). There were no significant differences between the fibrin-stented and
      bare-stented coronary segments with regard to arterial injury. In group 1 (28
      days, 14 pigs), the mean neointimal thicknesses in the fibrin-stented and bare
      stented groups were 0.57+/-0.31 and 0.57+/-0.27 mm, respectively (p=0.89). In
      groups 2 to 4 (90 days, four pigs; 6 months, four pigs; 1 year, five pigs), the
      mean neointimal thicknesses for fibrin- and bare-stented coronary segments at the
      times studied were 0.48+/-0.26 versus 0.50+/-0.22 mm at 90 days; 035+/-0.04
      versus 0.35+/-0.16 mm at 6 months; and 0.33+/-0.14 versus 0.30+/-0.14 mm at 1
      year (p=0.98). CONCLUSIONS: Fibrin-film stents appear to be an excellent
      candidate for local drug delivery because they can completely and safely cover
      the stented coronary segment while degrading slowly over 1 to 3 months. This
      result is important when compared with the poor results of previous studies of
      synthetic polymer stents.

PMID- 9581747
TI  - Paradoxical sinus deceleration during dobutamine stress echocardiography.

PMID- 9581748
TI  - F-18 FDG uptake in transplanted heart.

PMID- 9581749
TI  - QT dispersion as a marker of risk in patients awaiting heart transplantation?

PMID- 9581750
TI  - Echocardiography in Staphylococcus aureus bacteremia.

PMID- 9581751
TI  - Propagation velocity of left ventricular filling flow measured by color M-mode
      Doppler echocardiography.

PMID- 9581752
TI  - Is pharmacologic cardioversion of atrial fibrillation really preferable to
      electrical cardioversion?

PMID- 9581753
TI  - Before predicting survival in children with pulmonary hypertension and congenital
      heart disease...

PMID- 9581754
TI  - Flash decaging of tyrosine sidechains in an ion channel.
AB  - A nonsense codon suppression technique was employed to incorporate ortho
      nitrobenzyl tyrosine, "caged tyrosine," in place of tyrosine at any of three
      positions (93, 127, or 198) in the alpha subunit of the muscle nicotinic ACh
      receptor (nAChR) expressed in Xenopus oocytes. The ortho-nitrobenzyl group was
      then removed by 1 ms flashes at 300-350 nm to yield tyrosine itself while
      macroscopic currents were recorded during steady ACh exposure. Responses to
      multiple flashes showed (1) that each flash decages up to 17% of the tyrosines
      and (2) that two tyrosines must be decaged per receptor for a response. The
      conductance relaxations showed multiple kinetic components; rate constants (<0.1
      s(-1) to 10(3) s(-1)) depended on pH and the site of incorporation, and relative
      amplitudes depended on the number of prior flashes. This method, which is
      potentially quite general, (1) provides a time-resolved assay for the behavior of
      a protein when a mutant sidechain is abruptly changed to the wild-type residue
      and (2) will also allow for selective decaging of sidechains that are candidates
      for covalent modification (such as phosphorylation) in specific proteins in
      intact cells.

PMID- 9581755
TI  - Pavlovian conditioning, negative feedback, and blocking: mechanisms that regulate
      association formation.

PMID- 9581756
TI  - Tackling pain at the source: new ideas about nociceptors.

PMID- 9581757
TI  - Neuronal cell death.

PMID- 9581758
TI  - New directions in pain research: molecules to maladies.

PMID- 9581759
TI  - vab-8 is a key regulator of posteriorly directed migrations in C. elegans and
      encodes a novel protein with kinesin motor similarity.
AB  - Nervous system assembly requires the directed migrations of cells and axon growth
      cones along the dorsoventral and anteroposterior axes. Although guidance
      mechanisms for dorsoventral migrations are conserved from nematodes to mammals,
      mechanisms for anteroposterior migrations are unknown. In C. elegans, the gene
      vab-8, which specifically functions in posteriorly directed migrations, encodes
      two isoforms of a novel intracellular protein that act cell-autonomously in
      different migrations. VAB-8L, which contains a domain similar to kinesin-like
      motors, functions in all vab-8-dependent axon growth cone migrations. VAB-8S,
      which lacks this N-terminal domain, functions in a subset of vab-8-dependent cell
      migrations. Continuous expression of VAB-8L in the ALM mechanosensory neuron,
      which normally requires vab-8 early in its development for posteriorly directed
      cell migration, redirects its anteriorly projecting axon posteriorly. We propose
      that regulation of vab-8 activity is a mechanism for controlling the direction of
      cell and axon growth cone migrations.

PMID- 9581760
TI  - A role for Abl in Notch signaling.
AB  - Abl is an axonal tyrosine kinase that has yet to be clearly linked to a receptor;
      Notch is a receptor for which the signaling pathway remains incompletely
      understood. We show here that Notch and abl mutations interact synergistically to
      produce synthetic lethality and defects in axon extension. Surprisingly, we
      cannot account for these axonal aberrations on the basis of changes in cell
      identity. We show, moreover, that Notch is present in the growth cones of
      extending axons, and that the Abl accessory protein Disabled binds to a signaling
      domain of Notch in vitro. We therefore speculate that Disabled and Abl may play a
      role in Notch signaling in Drosophila axons, perhaps by binding to the Notch
      intracellular domain.

PMID- 9581761
TI  - SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family.
AB  - The PSD-95/SAP90 family of proteins has recently been implicated in the
      organization of synaptic structure. Here, we describe the isolation of a novel
      Ras-GTPase activating protein, SynGAP, that interacts with the PDZ domains of PSD
      95 and SAP102 in vitro and in vivo. SynGAP is selectively expressed in brain and
      is highly enriched at excitatory synapses, where it is present in a large
      macromolecular complex with PSD-95 and the NMDA receptor. SynGAP stimulates the
      GTPase activity of Ras, suggesting that it negatively regulates Ras activity at
      excitatory synapses. Ras signaling at the postsynaptic membrane may be involved
      in the modulation of excitatory synaptic transmission by NMDA receptors and
      neurotrophins. These results indicate that SynGAP may play an important role in
      the modulation of synaptic plasticity.

PMID- 9581762
TI  - CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD
      95/SAP90.
AB  - The synaptic protein PSD-95/SAP90 binds to and clusters a variety of membrane
      proteins via its two N-terminal PDZ domains. We report a novel protein, CRIPT,
      which is highly conserved from mammals to plants and binds selectively to the
      third PDZ domain (PDZ3) of PSD-95 via its C terminus. While conforming to the
      consensus PDZ-binding C-terminal sequence (X-S/T-X-V-COOH), residues at the -1
      position and upstream of the last four amino acids of CRIPT determine its
      specificity for PDZ3. In heterologous cells, CRIPT causes a redistribution of PSD
      95 to microtubules. In brain, CRIPT colocalizes with PSD-95 in the postsynaptic
      density and can be coimmunoprecipitated with PSD-95 and tubulin. These findings
      suggest that CRIPT may regulate PSD-95 interaction with a tubulin-based
      cytoskeleton in excitatory synapses.

PMID- 9581763
TI  - Ca2+ influx regulates BDNF transcription by a CREB family transcription factor
      dependent mechanism.
AB  - CREB is a transcription factor implicated in the control of adaptive neuronal
      responses. Although one function of CREB in neurons is believed to be the
      regulation of genes whose products control synaptic function, the targets of CREB
      that mediate synaptic function have not yet been identified. This report
      describes experiments demonstrating that CREB or a closely related protein
      mediates Ca2+-dependent regulation of BDNF, a neurotrophin that modulates
      synaptic activity. In cortical neurons, Ca2+ influx triggers phosphorylation of
      CREB, which by binding to a critical Ca2+ response element (CRE) within the BDNF
      gene activates BDNF transcription. Mutation of the BDNF CRE or an adjacent novel
      regulatory element as well as a blockade of CREB function resulted in a dramatic
      loss of BDNF transcription. These findings suggest that a CREB family member acts
      cooperatively with an additional transcription factor(s) to regulate BDNF
      transcription. We conclude that the BDNF gene is a CREB family target whose
      protein product functions at synapses to control adaptive neuronal responses.

PMID- 9581764
TI  - Identification of a signaling pathway involved in calcium regulation of BDNF
      expression.
AB  - A signaling pathway by which calcium influx regulates the expression of the major
      activity-dependent transcript of BDNF in cortical neurons has been elucidated.
      Deletion and mutational analysis of the promoter upstream of exon III reveals
      that transactivation of the BDNF gene involves two elements 5' to the mRNA start
      site. The first element, located between 72 and 47 bp upstream of the mRNA start
      site, is a novel calcium response element and is required for calcium-dependent
      BDNF expression in both embryonic and postnatal cortical neurons. The second
      element, located between 40 and 30 bp upstream of the mRNA start site, matches
      the consensus sequence of a cAMP response element (CRE) and is required for
      transactivation of the promoter in postnatal but not embryonic neurons. The CRE
      dependent component of the response appears to be mediated by CREB since it is
      part of the complex that binds to this CRE, and since dominant negative mutants
      of CREB attenuate transactivation of the promoter. A constitutively active mutant
      of CaM kinase IV, but not of CaM kinase II, leads to activation of the promoter
      in the absence of extracellular stimuli, and partially occludes calcium-dependent
      transactivation. The effects of CaM kinase IV on the promoter require an intact
      CRE. These mechanisms, which implicate CaM kinase IV and CREB in the control of
      BDNF expression, are likely to be centrally involved in activity-dependent
      plasticity during development.

PMID- 9581765
TI  - Brain control of embryonic circadian rhythms in the silkmoth Antheraea pernyi.
AB  - The clock protein PER is necessary for circadian control of egg-hatching behavior
      in the silkmoth Antheraea pernyi. Since the brain and midgut of the silkmoth
      embryo contain PER-positive cells, we examined the circadian clock potential of
      these embryonic tissues. Transplantation experiments indicate that the circadian
      clock controlling egg-hatching behavior resides in brain, and that a humoral
      factor mediates this circadian regulation. We also used ligation experiments on
      first instar larvae to show that the circadian control of PER movement into the
      nuclei of midgut epithelial cells is dependent on an intact (connected) brain.
      These results implicate a novel brain factor in the circadian regulation of egg
      hatching behavior and provide further evidence for differing mechanisms of PER
      control among species.

PMID- 9581766
TI  - Olfactory reciprocal synapses: dendritic signaling in the CNS.
AB  - Synaptic transmission between dendrites in the olfactory bulb is thought to play
      a major role in the processing of olfactory information. Glutamate released from
      mitral cell dendrites excites the dendrites of granule cells, which in turn
      mediate GABAergic dendrodendritic inhibition back onto mitral dendrites. We
      examined the mechanisms governing reciprocal dendritic transmission in rat
      olfactory bulb slices. We find that NMDA receptors play a critical role in this
      dendrodendritic inhibition. As with axonic synapses, the dendritic release of
      fast neurotransmitters relies on N- and P/Q-type calcium channels. The magnitude
      of dendrodendritic transmission is directly proportional to dendritic calcium
      influx. Furthermore, recordings from pairs of mitral cells show that
      dendrodendritic synapses can mediate lateral inhibition independently of axonal
      action potentials.

PMID- 9581767
TI  - Active currents regulate sensitivity and dynamic range in C. elegans neurons.
AB  - Little is known about the physiology of neurons in Caenorhabditis elegans. Using
      new techniques for in situ patch-clamp recording in C. elegans, we analyzed the
      electrical properties of an identified sensory neuron (ASER) across four
      developmental stages and 42 unidentified neurons at one stage. We find that ASER
      is nearly isopotential and fails to generate classical Na+ action potentials.
      Rather, ASER displays a high sensitivity to input currents coupled to a
      depolarization-dependent reduction in sensitivity that may endow ASER with a wide
      dynamic range. Voltage clamp revealed depolarization-activated K+ and Ca2+
      currents that contribute to high sensitivity near the zero-current potential. The
      depolarization-dependent reduction in sensitivity can be attributed to activation
      of K+ current at voltages where it dominates the net membrane current. The
      voltage dependence of membrane current was similar in all neurons examined,
      suggesting that C. elegans neurons share a common mechanism of sensitivity and
      dynamic range.

PMID- 9581768
TI  - Visualization of cyclic AMP-regulated presynaptic activity at cerebellar granule
      cells.
AB  - Adenylyl cyclase (AC) modulation of vesicular cycling was visualized at cultured
      cerebellar granule cell synapses using the sequential uptake of antibodies
      directed against the intraluminal domain of synaptotagmin I. Vesicle recycling
      due to spontaneous transmitter release in the absence of action potentials was
      increased by the AC/protein kinase A (PKA) activators forskolin and CPT-cAMP.
      These effects were blocked by the PKA inhibitor Rp-cAMPs. Cyclic AMP elevation
      also induced new cycling at previously silent sites. Activation of L-AP4
      sensitive mGluR reduced the cAMP/PKA enhancement at preexisting synapses
      downstream of both AC and calcium channels. Modulation of the turnover and the
      number of vesicular release sites provide one mechanism that may underlie cAMP
      dependent cerebellar long-term potentiation.

PMID- 9581769
TI  - Spillover-mediated transmission at inhibitory synapses promoted by high affinity
      alpha6 subunit GABA(A) receptors and glomerular geometry.
AB  - Divergence and convergence of synaptic connections make a crucial contribution to
      the information processing capacity of the brain. Until recently, it was thought
      that transmitter released at a synapse affected only a specific postsynaptic
      cell. We show here that spillover of inhibitory transmitter at the Golgi to
      granule cell synapse produces significant cross-talk to non-postsynaptic cells,
      which is promoted both by the anatomical specialization of this glomerular
      synapse and by the presence of the high affinity alpha6 subunit-containing
      GABA(A) receptor in granule cells. Cross-talk is manifested as a novel slow
      rising and decaying small amplitude inhibitory postsynaptic current (IPSC) that
      can also contribute a long-lasting component to more typical IPSCs, which is
      prolonged by inhibition of the neuronal GABA transporter GAT-1. Because of the
      long duration of IPSCs generated by spillover, the total charge carried is three
      times that of IPSCs generated by directly connected terminals. GABA spillover
      within the mossy fiber glomerulus may play an important role in regulating the
      number of granule cells active in the cerebellar cortex, a regulation that is
      suggested by theoretical models to optimize cerebellar information processing.

PMID- 9581770
TI  - Inactivation of presynaptic calcium current contributes to synaptic depression at
      a fast central synapse.
AB  - Voltage-gated calcium channels are well characterized at neuronal somata but less
      thoroughly understood at the presynaptic terminal where they trigger transmitter
      release. In order to elucidate how the intrinsic properties of presynaptic
      calcium channels influence synaptic function, we have made direct recordings of
      the presynaptic calcium current (I(pCa)) in a brainstem giant synapse called the
      calyx of Held. The current was pharmacologically classified as P-type and
      exhibited marked inactivation. The inactivation was largely dependent upon the
      inward calcium current magnitude rather than the membrane potential, displayed
      little selectivity between divalent charge carriers (Ca2+, Ba2+ and Sr+), and
      exhibited slow recovery. Simultaneous pre- and postsynaptic whole-cell recording
      revealed that I(pCa) inactivation predominantly contributes to posttetanic
      depression of EPSCs. Thus, because of its slow recovery, I(pCa) inactivation
      underlies this short-term synaptic plasticity.

PMID- 9581771
TI  - Deletion of the K(V)1.1 potassium channel causes epilepsy in mice.
AB  - Mice lacking the voltage-gated potassium channel alpha subunit, K(V)1.1, display
      frequent spontaneous seizures throughout adult life. In hippocampal slices from
      homozygous K(V)1.1 null animals, intrinsic passive properties of CA3 pyramidal
      cells are normal. However, antidromic action potentials are recruited at lower
      thresholds in K(V)1.1 null slices. Furthermore, in a subset of slices, mossy
      fiber stimulation triggers synaptically mediated long-latency epileptiform burst
      discharges. These data indicate that loss of K(V)1.1 from its normal localization
      in axons and terminals of the CA3 region results in increased excitability in the
      CA3 recurrent axon collateral system, perhaps contributing to the limbic and
      tonic-clonic components of the observed epileptic phenotype. Axonal action
      potential conduction was altered as well in the sciatic nerve--a deficit
      potentially related to the pathophysiology of episodic ataxia/myokymia, a disease
      associated with missense mutations of the human K(V)1.1 gene.

PMID- 9581772
TI  - Cellular factors in the transcription and replication of viral RNA genomes: a
      parallel to DNA-dependent RNA transcription.
AB  - Viral RNA replication and transcription involves not only viral RNA-dependent RNA
      polymerases, but also cellular proteins, the majority of which are subverted from
      the RNA-processing or translation machineries of host cells. These factors
      interact with viral RNA or polymerases to form transcription or replication
      ribonucleoprotein complexes and may provide template specificity for RNA
      dependent RNA synthesis, suggesting a close parallel to the mechanism of DNA
      dependent RNA synthesis. The types of cellular proteins involved and their modes
      of action are reviewed.

PMID- 9581773
TI  - Intersubunit interactions allowing a carboxylate mutant coat protein to inhibit
      tobamovirus disassembly.
AB  - Tobacco mosaic tobamovirus (TMV) coat protein (CP) mutant E50Q lacks a repulsive
      intersubunit carboxylate group and can effectively inhibit the disassembly of
      wild-type TMV (Culver et al, 1995, Virology 206,724). To investigate the ability
      of this mutant CP to block disassembly, a series of second-site amino acid
      substitutions were added to the E50Q CP. These second-site mutations were
      designed to disrupt specific intersubunit stabilizing interactions involving
      hydrophobic or polar residues, salt bridges, and CP-RNA contacts. Results showed
      substitutions disrupting intersubunit interactions that face the disassembling
      surface of the virion dramatically reduced the ability of CP E50Q to inhibit TMV
      disassembly. Substitutions that disrupted the CP inner loop, RNA binding
      capabilities, or intersubunit interactions that faced away from the disassembling
      surface did not dramatically interfere with CP E50Q's ability to inhibit
      disassembly. Taken together, these findings suggest that intersubunit
      interactions made by 5' terminal E50Q subunits, not associated with RNA, provide
      the stabilizing forces that prevent virion disassembly. The role of these
      stabilizing interactions in TMV disassembly and their potential use for creating
      disassembly inhibiting CPs are discussed.

PMID- 9581774
TI  - Role for the vaccinia virus A36R outer envelope protein in the formation of virus
      tipped actin-containing microvilli and cell-to-cell virus spread.
AB  - A small-plaque-forming vaccinia virus mutant with a deletion in the A36R gene
      encoding an outer envelope protein (Parkinson and Smith, Virology, 204, 376-390,
      1994) was shown to assemble wrapped forms of intra- and extracellular virus
      particles and to mediate acid-induced polykaryon formation. The intracellular
      virions, however, did not acquire actin tails and those on the cell surface were
      not associated with specialized microvilli. This phenotype is similar to that of
      the A34R (E. J. Wolffe, E. Katz, A. Weisberg, and B. Moss, J. Virol 71, 3904
      3915, 1997) and A33R (R. Roper, E. J. Wolffe, A. Weisberg, and B. Moss, J.
      Virol., in press) deletion mutants. Taken together, these data support a model in
      which the envelope proteins encoded by the A33R, A34R, and A36R genes are all
      required for nucleation of actin tails, which facilitate dissemination rather
      than egress of virus particles.

PMID- 9581776
TI  - Effects of Vpu expression on Xenopus oocyte membrane conductance.
AB  - The HIV-1-specific vpu gene encodes an integral membrane phosphoprotein which
      affects three aspects of the HIV-1 infectious cycle: it enhances virion release
      from infected cells; it causes degradation of the CD4 protein in the endoplasmic
      reticulum; and it delays syncytia formation in HIV-1-infected CD4+ T-cells.
      Although little is known about how Vpu mediates these effects, it has been
      proposed to function as a nonspecific cation channel. In this report, voltage
      clamp measurements of Xenopus oocytes show that Vpu expression is not associated
      with increased transmembrane currents. Instead, Vpu expression diminishes
      membrane conductance. Injection of 4.6 ng of Vpu mRNA into these cells reduces
      endogenous potassium conductance by 50%. Only Vpu mutants which retain the
      ability to degrade CD4 can diminish K+ conductance. Inhibition by Vpu is not
      unique to K+ channels as it is also observed on several coexpressed membrane
      proteins but not on a coexpressed cytoplasmic protein. These results indicate
      that the CD4 degradative capability of Vpu and the Vpu-mediated modulation of
      membrane protein expression are mechanistically coupled and that Vpu may
      contribute to HIV pathogenesis by altering plasma membrane protein expression at
      the cell surface.

PMID- 9581775
TI  - NF-kappaB protects HIV-1-infected myeloid cells from apoptosis.
AB  - HIV-1 infection of primary monocytic cells and myeloid cell lines results in
      sustained NF-kappaB activation. Recently, NF-kappaB induction has been shown to
      play a role in protecting cells from programmed cell death. In the present study,
      we sought to investigate whether constitutive NF-kappaB activity in chronically
      HIV-1-infected promonocytic U937 (U9-IIIB) and myeloblastic PLB-985 (PLB-IIIB)
      cells affects apoptotic signaling. TNFalpha and cycloheximide caused infected
      cells to undergo apoptosis more rapidly than parental U937 and PLB-985 cells.
      Inhibition of TNFalpha-induced NF-kappaB activation using the antioxidant N
      acetylcysteine (NAC) resulted in increased apoptosis in both U937 and U9-IIIB
      cells, while preactivation of NF-kappaB with the non-apoptotic inducer IL-1beta
      caused a relative decrease in apoptosis. Inhibition of constitutive NF-kappaB
      activity in U9-IIIB and PLB-IIIB cells also induced apoptosis, suggesting that NF
      kappaB protects cells from a persistent apoptotic signal. TNFalpha plus NAC
      treatment resulted in a marked decrease in Bcl-2 protein levels in HIV-1-infected
      cells, coupled with an increase in Bax protein compared to uninfected cells,
      suggesting that the difference in susceptibility to TNFalpha-induced apoptosis
      may relate to the differences in relative levels of Bcl-2 and Bax. The protective
      role of NF-kappaB in blocking TNFalpha- and HIV-1-induced apoptosis was supported
      by studies in Jurkat T cells engineered to express IkappaB alpha repressor
      mutants (TD-IkappaB) under the control of a tetracycline-responsive promoter.
      Cells underwent apoptosis in response to TNFalpha only when NF-kappaB activation
      was inhibited by TD-IkappaB expression. As was observed for the U9-IIIB cells,
      TNFalpha treatment also induced a marked decrease in Bcl-2 protein levels in TD
      IkappaB expressing cells. These experiments demonstrate that apoptotic signaling
      is perturbed in HIV-1-infected U9-IIIB cells and indicate that NF-kappaB
      activation may play an additional protective role against HIV-1-induced apoptosis
      in myeloid cells.

PMID- 9581777
TI  - An insect picorna-like virus, Plautia stali intestine virus, has genes of capsid
      proteins in the 3' part of the genome.
AB  - The complete genome of an insect picorna-like virus, Plautia stali intestine
      virus (PSIV), was cloned and sequenced. The genome had 8797 nucleotides including
      two consecutive long open reading frames. The deduced amino acid sequence of the
      first open reading frame (nucleotides 571 to 6003) contained conserved sequence
      motifs for picornavirus RNA helicase, cysteine protease, and RNA-dependent RNA
      polymerase. The order of the three motifs in the genome was the same as those of
      mammalian picornaviruses. The coding regions of four capsid proteins (33, 30, 26,
      and 4.5 kDa) were mapped by determining their N-terminal sequences. Unlike
      mammalian picornaviruses, the genes for these proteins were in the 3' region of
      the PSIV genome. In vitro translation assay suggested that the capsid protein
      precursor of PSIV would be translated by internal initiation. The deduced amino
      acid sequence of the capsid proteins showed homology to those of the proteins
      encoded in the 3' part of the genomes of widely distributed insect picorna-like
      viruses, cricket paralysis virus, and Drosophila C virus. Some insect picorna
      like viruses would have the same unique coding strategy as PSIV.

PMID- 9581778
TI  - Mutation in a 17D-204 vaccine substrain-specific envelope protein epitope alters
      the pathogenesis of yellow fever virus in mice.
AB  - The heterogeneous nature of the yellow fever (YF) 17D-204 vaccine virus
      population was exploited in this study to isolate virus variants able to escape
      neutralization by the 17D-204 vaccine-specific MAb 864. The conformational change
      on the virus surface that resulted in the loss of the MAb 864-defined epitope was
      effected in each variant by a single amino acid mutation in the envelope (E)
      protein at either position E-305 or E-325. Interestingly, both positions were
      mutated during attenuation of the 17D-204 vaccine substrain from the wildtype
      Asibi strain. The mutations in several of the variants represented reversion to
      the wildtype Asibi virus sequence consistent with loss of a 17D-204 substrain
      specific epitope. The majority of the variant viruses were shown to have altered
      mouse neurovirulence phenotypes, ranging from complete avirulence through to
      increased virulence. The avirulent variants are the first flavivirus MAb
      neutralization-resistant variants to be attenuated for neurovirulence in the
      adult mouse model. Overall, the results indicate that the E protein epitope
      recognized by MAb 864 defines a functionally important region that encodes major
      molecular determinants of YF virus pathogenesis in vivo.

PMID- 9581779
TI  - Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected
      individuals: association with low expression of CCR5 and high production of beta
      chemokines.
AB  - We examined the human immunodeficiency virus type 1 infectability of CD4+
      lymphocytes isolated from CCR5 wild-type individuals, individuals heterozygous
      for the delta32 allele of CCR5, and HIV-1-exposed but uninfected (EU) individuals
      who had CD4+ lymphocytes refractory to M-tropic viral replication. None of the EU
      individuals were found to be heterozygous for the delta32 allele. The CD4+
      lymphocytes isolated from CCR5/delta32 and EU individuals were less infectable
      with an M-tropic viral isolate of HIV-1 than CCR5/CCR5 control individuals but
      were equally as infectable with a T-tropic viral isolate. The restriction to M
      tropic viral isolate replication did not associate with any profound genotypic
      change in the CCR5 gene. CD4+ lymphocytes from CCR5/delta32 and CCR5/CCR5 EU
      individuals were more sensitive to the HIV-inhibitory effects of the recombinant
      beta-chemokines RANTES, MIP-1alpha, and MIP-1beta than were CD4+ lymphocytes from
      CCR5/CCR5 control individuals. CD4+ lymphocytes from EU individuals also showed
      increased sensitivity to recombinant beta-chemokines and low surface expression
      of CCR5. A phenotype of low CCR5 expression and high secretion of beta-chemokines
      is associated with reduced infectability of cells by M-tropic HIV-1. This
      phenotype may also be associated with protection against sexual transmission of
      HIV-1.

PMID- 9581780
TI  - Membranes of herpes simplex virus type-1-infected human corneal epithelial cells
      are not permeabilized to macromolecules and therefore do not release IL-1alpha.
AB  - Nanogram amounts of the proinflammatory cytokine interleukin-1alpha (IL-1alpha)
      were detected in uninfected cultures of human corneal epithelial cells (HCEC).
      Although HSV-1 replicated >10(4)-fold in these cells and caused extensive
      cytopathic effects, virus infection was not accompanied by significant
      extracellular release of IL-1alpha. Additional studies showed that release of
      radiolabeled cytosolic proteins from virus-infected HCEC was no greater than that
      released by mock-infected cells. These findings indicate that HSV-1 infection of
      HCEC does not result in IL-1alpha release because newly formed virus progeny can
      escape infected cells without disrupting cell membranes.

PMID- 9581781
TI  - Expression of the rice yellow mottle virus P1 protein in vitro and in vivo and
      its involvement in virus spread.
AB  - Rice yellow mottle sobemovirus (RYMV) is responsible for the yellow mottle
      disease on rice in Africa. The expression and function of the protein P1 (17.8
      kDa) encoded by the first open reading frame (ORF) of RYMV was investigated.
      Using an antibody raised against purified P1, two proteins with apparent
      molecular masses of 18 and 19 kDa were identified in in vitro translation
      reactions of transcripts of the full-length cDNA of RYMV. Likewise, gene products
      with similar molecular mass were detected in inoculated and systemically infected
      rice leaves and in infected rice protoplasts. A mutant from which ORF1
      nucleotides 88 to 547 were deleted and a frameshift mutant that resulted in
      truncation of 83 amino acids from the C terminus of P1 were incapable of
      replicating in protoplasts. In contrast, a mutant that does not express P1 due to
      a mutation at the initiation codon replicated efficiently in protoplasts but at a
      reduced level (about 0.5- to 2-fold less) compared to replication of wild-type
      RNA. None of these mutants caused systemic infection in rice plants. Transgenic
      rice plants that express P1 complemented the initiation codon mutant, but not the
      deletion mutants, and produced systemic infection. These experiments demonstrate
      that P1 of RYMV is dispensible for virus replication, although nucleotide
      deletions or additions in ORF1 are apparently lethal for virus replication.
      Furthermore, P1 of RYMV is required for the infection of plants and is important
      for virus spread.

PMID- 9581782
TI  - Regulation of intracellular human immunodeficiency virus type-1 protease
      activity.
AB  - The maturation of HIV-1 virions is accomplished through the proteolytic cleavage
      of Gag and GagPol precursor polyproteins by the viral-encoded protease (PR).
      Since virions are assembled from unprocessed polyproteins, the intracellular
      activation of PR must be limited. An experimental system was established that
      allows the investigation of the intracellular regulation of PR activity. By
      expressing Gag in trans with the GagPol precursor, downregulation of the
      intracellular PR activity associated with GagPol was demonstrated. Inhibition of
      PR activity was dependent upon the context of PR expression. Sequences capable of
      mediating this inhibition were localized to capsid. A mechanism through which Gag
      regulates PR activity is proposed whereby the disproportionate synthesis of Gag
      inhibits the activation of PR in the cytoplasm. Further elucidation of the
      mechanism of intracellular inhibition of PR activity may facilitate the
      development of novel PR inhibitors capable of inhibiting viral replication in
      vivo.

PMID- 9581783
TI  - The early HPV16 proteins can regulate mRNA levels of cell cycle genes in human
      cervical carcinoma cells by p53-independent mechanisms.
AB  - Cervical carcinoma-associated human papillomavirus type 16 (HPV16) encodes E6 and
      E7 oncoproteins which inactivate p53 and Rb, respectively, but these interactions
      are not sufficient to account for the oncogenic potential of the virus. Several
      viral promoters were shown to be regulated by E6 and E7. To identify genes as
      cellular targets of the HPV16 early proteins, we transfected a new HPV-negative
      and p53-mutated cervical carcinoma-derived cell line with either the HPV16 full
      length genome or the HPV16 E6 gene. HPV16 clones but not 16E6 clones showed a
      decreased doubling time that was not related to the viral DNA and mRNA patterns.
      In exponentially growing cells as well as in cells synchronized by serum
      starvation, expression of the E6 gene was associated with upregulation of the c
      fos and c-jun proto-oncogenes and with downregulation of the c-Ha-ras gene.
      Furthermore, a viral gene other than E6 may be involved in downregulation of p53
      because a reduced mRNA level at the G1/S transition was observed only in HPV16
      cells. The present study on natural host cells indicates p53-independent
      transcriptional modulations of cell cycle regulatory genes related to HPV16 E6
      and E7 expression.

PMID- 9581784
TI  - Inhibition of ICE-like proteases inhibits apoptosis and increases virus
      production during adenovirus infection.
AB  - Interleukin-1b converting enzyme (ICE)-related cysteine proteases are required
      for E1A-induced, p53-dependent apoptosis in baby rat kidney (BRK) cells.
      Adenovirus E1B 19K protein, which is a potent inhibitor of apoptosis, inhibits
      activation of these proteases in BRK cells. E1A expression induces apoptosis
      during infection of human cells by mutant adenoviruses which contain
      nonfunctional E1B 19K. The question arises as to whether ICE-related proteases
      are involved in E1A-induced apoptosis during mutant adenovirus infection of human
      cells. To test the involvement of the cysteine proteases in E1A-induced apoptosis
      during productive adenovirus infection of HeLa cells, we examined whether Z-VAD
      FMK, an inhibitor of ICE-related proteases, can inhibit apoptosis induced by
      mutant adenovirus which lacks functional E1B 19K. Z-VAD-FMK inhibited E1A-induced
      apoptosis in adenovirus-infected Hela cells, suggesting that the ICE family
      proteases are involved in this apoptosis pathway. Z-VAD-FMK also inhibited
      cleavage of substrates such as cysteine protease CPP32 and nuclear lamins,
      whereas cleavage of poly(ADP-ribose) polymerase was partially inhibited during
      infection with an E1B 19K mutant. Inhibition of apoptosis by Z-VAD-FMK
      significantly enhanced production of infectious adenovirus and attenuated virus
      release. Thus apoptosis may be a method for the host cell to limit virus
      production and release at the end of the infection cycle.

PMID- 9581785
TI  - The DNA sequence of the RK strain of human herpesvirus 7.
AB  - The complete DNA sequence of human herpesvirus-7 (HHV-7) strain RK was determined
      following direct cloning of virion DNA fragments into a sequencing vector. The
      sequence was compared with the previously published complete sequences of HHV-7
      strain JI and human herpesvirus-6 (HHV-6) strain U1102. Despite a very close
      relationship between the two HHV-7 strains, differences are apparent in regions
      containing tandem reiterations, particularly in the "telomeric" reiterations
      located near the termini of the large direct repeat at the genome ends, and in a
      total of 179 additional positions distributed throughout the genome (i.e., about
      one nucleotide difference per kbp). This extent of divergence implies that the
      two strains arose from an ancestral virus several thousands of years ago.
      Differences that affect coding potential do not cluster in particular protein
      coding regions, indicating that specific HHV-7 genes have not been measurably
      subject to unusual evolutionary pressures since divergence. Reassessments of
      genetic content indicated that the HHV-7 genome contains 84 different genes,
      whereas the HHV-6 genome contains 85. All HHV-7 genes but 1 have direct HHV-6
      counterparts, and all but 2 HHV-6 genes have HHV-7 homologues. Sequence
      comparisons between HHV-7 and HHV-6 provided evidence that the protein-coding
      regions of 11 genes are expressed by splicing.

PMID- 9581786
TI  - Mutational analysis of stem-loops in the RNA packaging signal of the Moloney
      murine leukemia virus.
AB  - The retroviral RNA genome is targeted for incorporation into the nascent virion
      particle by the psi region, a specific block of RNA sequences near the 5' end. A
      number of deletions and linker insertion mutations were introduced into the psi
      region of cloned DNA of the Moloney murine leukemia virus, and the mutants were
      introduced into cells in culture and tested for their ability to direct the
      assembly of virions and the packaging of viral RNA. Only a small portion of the
      psi region was important for packaging, containing the so-called stem-loops C and
      D. Additional mutants were used to demonstrate that the base pairing of stem D,
      and the sequence of loop D, were essential for normal packaging of the RNA. Two
      mutants with alterations near the 5' splice donor were also replication
      defective, probably due to effects on gene expression. The results allow a high
      resolution definition of the RNA structures required during virus replication in
      culture.

PMID- 9581787
TI  - Analysis of hepatitis B virus populations in an interferon-alpha-treated patient
      reveals predominant mutations in the C-gene and changing e-antigenicity.
AB  - It is largely unknown whether hepatitis B virus (HBV) sequence variation during
      chronic infection hampers HBV immune recognition or the antiviral effect of
      cytokines on HBV production. Here we have analyzed which region of the HBV genome
      changes most drastically during an interferon-alpha (IFNalpha)-stimulated immune
      response. In addition, we have investigated whether the mutations affect viral
      replication, gene expression, and immune recognition of the mutant viral
      proteins. The study was performed with full-length HBV genomes taken
      longitudinally from a patient who transiently cleared HBV and seroconverted to
      anti-HBe during a long-term IFNalpha treatment. We found a replacement of the
      predominant virus population during IFNalpha therapy The virus populations
      differed mainly by a cluster of nucleotide changes in the C-gene and a pre-S2
      deletion. Most of the newly emerging mutations localized within core/HBe B-cell
      epitopes, changed HBe antigenicity toward mono- and polyclonal antibodies, and
      also influenced the reactivity of the anti-HBc/e antibodies of the patient. All
      genomes tested expressed less HBeAg than wild-type HBV, while replication and
      IFNalpha susceptibility were similar. These data indicate that IFNalpha therapy
      can lead to the emergence of HBV variants with mutations mainly affecting
      recognition of the core/HBe proteins by antibodies. Taken together, the type of
      core/HBe-specific B-cell immune response, the sequence of the corresponding
      epitopes, and the HBe expression level appear to contribute to the decision on
      viral clearance or persistence.

PMID- 9581788
TI  - Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are
      infectious in vivo.
AB  - We constructed a chimeric cDNA clone of hepatitis C virus (HCV) that is
      infectious. The chimeric genome encodes the polyprotein of a genotype 1b strain
      (HC-J4) of HCV and replicates via 5' and 3' untranslated regions of a genotype 1a
      strain. The infectivity of three full-length cDNA clones was tested by direct
      injection of RNA transcripts into the liver of a chimpanzee. The chimpanzee
      became infected with HCV and the viral titer increased over time from 10(2)
      genome equivalents (GE)/ml at week 1 postinoculation (p.i.) to 10(4)-10(5) GE/ml
      during weeks 3-11 p.i. Antibodies to HCV were detected from week 18 p.i. However,
      the chimpanzee did not develop hepatitis. Sequence analysis of PCR products
      amplified from the serum of the chimpanzee demonstrated that only one of the
      three clones was infectious. Sequence comparisons with the cloning source, an
      acute-phase infectious plasma pool derived from an experimentally infected
      chimpanzee, showed that this infectious clone had three amino acids that differed
      from the consensus sequence of HC-J4, whereas the two noninfectious clones had
      seven and nine amino acid differences, respectively. Together, genotype 1b,
      represented by the infectious molecular clone described herein, and genotype 1a,
      represented by the two cDNA clones previously shown to be infectious for
      chimpanzees, account for the majority of HCV infections in the United States,
      Europe, and Japan.

PMID- 9581789
TI  - Sequence, transcriptional analysis, and deletion of the bovine adenovirus type 1
      E3 region.
AB  - The early 3 (E3) transcriptional unit of human adenoviruses (HAV) encodes
      proteins that modulate host antiviral immune defenses. HAV E3 sequences are
      highly variable; different HAV groups encode phylogenetically unrelated proteins.
      The role of the E3 region of many human and animal adenoviruses is unknown
      because the sequences are unrelated to previously characterized viruses and the
      functions of proteins encoded by these regions have not been studied. We
      sequenced a portion of the bovine adenovirus serotype 1 (BAV-1) genome
      corresponding to the putative E3 region. This sequence was substantially
      different from other adenoviral E3 sequences, including those of two other bovine
      adenoviruses. However, two regions of putative sequence conservation were
      identified. BAV-1 E3 sequences were identified in early and late transcripts,
      but, unlike HAV, introns were not detected in the E3 region transcripts. Like HAV
      E3, a majority of the BAV-1 E3 region was not essential for growth in cell
      culture, as demonstrated by the construction of a recombinant BAV-1 lacking 60%
      of the putative E3 region.

PMID- 9581790
TI  - Tomato spotted wilt Tospovirus genome reassortment and genome segment-specific
      adaptation.
AB  - A system to associate specific genome segments with viral phenotypes and to study
      factors influencing genome reassortment was developed for tomato spotted wilt
      Tospovirus (TSWV). Reassortant isolates were generated by co-inoculating a TSWV
      isolate, TSWV-D, with TSWV-10 or TSWV-MD. The parental origin of each genome
      segment in putative reassortant isolates was determined by segment-specific
      restriction fragment length polymorphisms. The TSWV isolates readily exchanged
      genome segments in a nonrandom fashion. The S RNA from TSWV-D was dominant over
      the S RNA from TSWV-10. The intergenic region (IGR) of the S RNA was correlated
      with competitiveness of this genome segment in reassortant isolates. The less
      competitive S RNA contained a net increase of 62 nt, including a 33-nt
      duplication in the IGR. This duplicate sequence was highly conserved among
      isolates from the southeastern United States and an isolate from Bulgaria. The
      evidence supports the hypothesis that the IGR of the S RNA with an ambisense
      coding strategy serves a regulatory function which influences the occurrence of
      this segment in the viral population. In addition, it was demonstrated that
      stable parental phenotypes can be mapped to specific genome segments as well as
      generating novel phenotypes not associated with either parent.

PMID- 9581791
TI  - Autographa californica nucleopolyhedrovirus infection results in Sf9 cell cycle
      arrest at G2/M phase.
AB  - Baculovirus infection results in the induction of membrane structures within the
      nucleoplasm of the host cells. The source of these membranes is unclear; however,
      using the normal dynamics of cellular membranes and the nuclear envelope as a
      model, it is possible that the cell cycle might play a role in the regulation of
      formation of these intranuclear membranes. Therefore, one goal of this study was
      to investigate the effect of baculovirus infection on the cell cycle of Sf9 host
      cells. Since few data are available on the cell cycle of insect cells, the first
      task was to define Sf9 cell cycle kinetics. The cell cycle phase distribution of
      Sf9 cells grown in suspension culture was determined to be evenly distributed
      (29% of the cells in G1, 33% in S, and 36% in G2/M phase), with the duration of
      G1 and S phases both being about 6 h and the combined duration of G2/M phase
      being about 8 h. When Sf9 cells were infected with AcMNPV (Autographa californica
      nuclear polyhedrosis virus), approximately 84% of the cells were arrested in G2/M
      phase by 18-24 h p.i. Concomitant with the viral-induced arrest in G2/M phase,
      high levels of both cdc2-associated histone H1 kinase activity and cyclin B
      protein were detected. By 24 h p.i. cyclin B was no longer detected; however,
      cdc2-associated histone H1 kinase activity remained throughout the infection.
      These data suggested that early in infection, cyclin B/cdc2 complex may be used
      to regulate the transition from G2 to M phase, but prolonged arrest may be due to
      a protein(s) encoded by AcMNPV. DNA hybridization analysis showed that the
      maximal rate of viral DNA replication occurred before G2/M arrest. We noted that
      viral DNA replication still occurred late in infection, when the majority of the
      cells were arrested in G2/M phase. Since cellular DNA replication normally does
      not occur during G2 or M phase, experiments were designed to determine if viral
      DNA replication could occur even when host cell DNA replication was arrested. Sf9
      cells were arrested and "frozen" at the boundary of G1/S phase using 5-fluoro
      2'deoxyuridine (FdUrd) treatment and then infected with AcMNPV In the blocked,
      infected cells, viral DNA replication was detected; however, cellular DNA
      remained at steady-state levels. These results suggested that cellular DNA
      replication was not necessary for viral DNA replication and show that viral DNA
      replication was not significantly inhibited by FdUrd treatment. It was a surprise
      to detect viral DNA replication when the host cells were "frozen" at G1/S phase.
      We wanted to determine if the viral infection was progressing to the stage of
      progeny virus production. Our data showed that progeny budded virus (BV) and
      virus-induced intranuclear microvesicles were produced in the frozen, infected
      cells; however, the intranuclear microvesicles had an unusual structure. They
      were irregular in shape and thickened compared to those observed in a normal
      infection. Very few enveloped nucleocapsids were visible in the nucleus of the
      frozen, infected cells and the occluded-derived virus envelope proteins, ODV-E66
      and ODV-EC27, were not detected by Western blot analyses. Since the cells were
      sustained at the boundary of G1 and S phases for the duration of this experiment,
      the decreased amount of enveloped ODV in the nucleus could be due to several
      factors, including decreased levels of proteins expressed from late genes,
      aberrant microvesicles, or the necessity of G2/M phasing of the infected cell for
      efficient production and maturation of intranuclear microvesicles. These data
      indicate that AcMNPV infection results in cell cycle arrest in G2/M phase and
      this arrest may be due to a viral-encoded protein(s) that has cdc2-associated
      kinase activity. (ABSTRACT TRUNCATED)

PMID- 9581792
TI  - Comparison of the native CCMV virion with in vitro assembled CCMV virions by
      cryoelectron microscopy and image reconstruction.
AB  - Cryoelectron microscopy and three-dimensional image reconstruction analysis has
      been used to determine the structure of native and in vitro assembled cowpea
      chlorotic mottle virus (CCMV) virions and capsids to 25-A resolution. Purified
      CCMV coat protein was used in conjunction with in vitro transcribed viral RNAs to
      assemble RNA 1 only, RNA 2 only, RNA 3/4 only, and empty (RNA lacking) virions.
      The image reconstructions demonstrate that the in vitro assembled CCMV virions
      are morphologically indistinguishable from native virions purified from infected
      plants. The viral RNA (vRNA) is packaged similarly within the different types of
      virions. The centers of all assembled particles are generally devoid of density
      and the vRNA packs against the interior surface of the virion shell. The vRNA
      appears to adopt an ordered conformation at each of the quasi-threefold axes.

PMID- 9581793
TI  - Coamplification and dispersion of adjacent human endogenous retroviral HERV-H and
      HERV-E elements; presence of spliced hybrid transcripts in normal leukocytes.
AB  - In an RT-PCR study of HERV-H spliced subgenomic transcripts, we found transcripts
      with HERV-H leader and protease-encoding sequences spliced to HERV-E integrase
      encoding sequences in lymphocytes from healthy blood donors. In other cell types,
      including two T-cell leukemia cell lines, these transcripts were absent. The PCR
      fragments of the hybrid transcripts contained two open reading frames (ORFs). One
      was a hybrid HERV-H protease/HERV-E integrase ORF and the other was the HERV-E
      envelope surface glycoprotein ORF. Alternative splice products were also
      identified. The genomic DNA origin of the hybrid transcripts was shown to be a
      HERV-H element with a large 3'-end deletion, adjacent to a HERV-E element lacking
      the 5'-LTR. This hybrid structure was shown to be amplified and dispersed to six
      different human chromosomes. Thus, a relatively large part of full-length HERV-E
      elements (15-20%) is potentially under the transcriptional control of HERV-H
      LTRs. The HERV-H/HERV-E junction was present in multiple copies also in the
      chimpanzee and gorilla, but not in the orangutan or old world monkeys.

PMID- 9581794
TI  - Regeneration of the binding properties of adenovirus 12 early region 1A proteins
      after preparation under denaturing conditions.
AB  - Adenovirus 12 early region 1A (Ad12 E1A) was expressed in Escherichia coli.
      Protein was purified in good yield in the presence of 8 M urea and then renatured
      by dialysis against dilute NH4HCO3 buffer. The affinity of this protein for pRb,
      C-terminal binding protein (CtBP), TATA binding protein (TBP), and SUG1 was
      similar to, or greater than, that of Ad12 E1A prepared by immunoaffinity
      chromatography under nondenaturing conditions. While the binding of the 266- and
      235-amino-acid (aa) E1A components to TBP showed similar characteristics the
      larger E1A protein had a higher affinity for CtBP, pRb, and SUG1. Using nuclear
      magnetic resonance (NMR) spectroscopy it was shown that structural perturbations
      occurred in the 266-aa protein in the presence of Zn2+ consistent with binding-
      no such changes were seen for the 235-aa protein. Limited proteolysis of the 266-
      and 235-aa E1A proteins gave rise to comparable polypeptide products, suggesting
      overall similarities in structure. However, the different affinities of the 266-
      and 235-aa proteins for the partner proteins and the differences seen in the NMR
      spectra from the two proteins suggested structural differences.

PMID- 9581795
TI  - Signal transduction by immunoglobulin Fc receptors.
AB  - Receptors for the Fc portion of immunoglobulin molecules (FcR) present on
      leukocyte cell membranes mediate a large number of cellular responses that are
      very important in host defense. Cross-linking of FcR by immune complexes leads to
      functions such as phagocytosis, cell cytotoxicity, production and secretion of
      inflammatory mediators, and modulation of the immune response. Molecular
      characterization of FcRs indicates the existence of several types of these
      receptors, which seem to be redundant in their cell distribution and function.
      There is a great deal of interest in understanding how these various receptors
      signal the cell to respond in different ways during inflammation and the immune
      response. Previous studies indicate that FcR signaling shares elements with the T
      and B cell antigen receptors. Signaling is initiated in all of them by activation
      of tyrosine kinases of the Src and ZAP-70 families. Subsequent events, which vary
      depending on the cell type and receptor involved, include activation of other
      enzymes such as phospholipase Cgamma1, phosphatidylinositol-3-kinase, and mitogen
      activated protein kinase. Several recent lines of research, including studies of
      phagocytosis by FcR-transfected cells, antibody-dependent cytotoxicity by natural
      killer cells, mast cell degranulation, and FcR-deficient mice, have given us new
      insights on the signal transduction pathways activated by FcRs. This review
      describes the advances in these areas and presents a general model for FcR
      mediated signaling.

PMID- 9581796
TI  - Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic
      sinusoid.
AB  - During the innate immune response, excessive release of reactive oxygen species
      (ROS) from sequestered phagocytes and activated resident macrophages represents
      the predominant component of oxidative stress in the liver and other tissues. The
      consequence of oxidative stress is determined by the status and adaptive changes
      of antioxidant pathways. In this review, we present evidence that the
      synchronized response of hepatic sinusoidal endothelial cells, the primary sites
      of phagocyte attachment, plays an important role in defense against phagocyte
      derived ROS. An essential component of the metabolic adaptation of hepatic
      sinusoidal cells to lipopolysaccharide (LPS)-induced oxidative stress is the
      stimulated expression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme
      of the pentose cycle (hexose monophosphate shunt, HMS). All major ROS-metabolic
      enzymes, i.e., glutathione peroxidase, glutathione reductase, catalase,
      superoxide dismutases, NADPH oxidase, and nitric oxide synthase, directly or
      indirectly depend on NADPH, which is produced in the HMS in these cells. The
      functional significance of up-regulated HMS within a particular cell type depends
      on the accompanying adaptive changes in ROS-metabolizing enzymes. In LPS
      activated Kupffer cells, the elevated expression of glucose transporter GLUT1 and
      G6PD mainly serves primed production of superoxide anion, hydrogen peroxide, and
      nitric oxide. In sinusoidal endothelial cells, the LPS-induced response pattern
      of glucose- and ROS-metabolizing enzymes results in elevated ROS detoxifying
      capacity. The described studies also suggest the existence of an intercellular
      oxidant balance between pro-oxidant Kupffer cells and antioxidant endothelial
      cells in the hepatic micro-environment. Maintenance of the intercellular
      oxidant/antioxidant balance between phagocytes and endothelial cells may
      represent an important mechanism protecting the hepatic parenchyma against
      exogenous oxidative stress during the inflammatory response.

PMID- 9581797
TI  - Specific Th1 cell lines that confer protective immunity against experimental
      Borrelia burgdorferi infection in mice.
AB  - Although humoral responses to Borrelia burgdorferi (Bb) have been shown to be
      protective in some animal models of Lyme disease, the role of T cells in this
      disease is less well understood. This work describes three Bb-specific T cell
      lines that prevent disease progression in syngeneic mice. The T cell lines were
      generated in C3H mice immunized with Bb in complete Freund's adjuvant. All lines
      were Bb-specific, CD4+, TCRalphabeta+, and they proliferated and produced
      interferon-gamma and interleukin-2 on stimulation with Bb. Injection of the cell
      lines into naive C3H recipients significantly reduced the number of organisms
      recoverable from the blood and tissues of infected mice and protected them from
      developing Bb-induced periarthritis. These studies demonstrated that Th1 cells
      can confer resistance to Bb infection in susceptible mice and suggested that the
      timing of this T cell response may be critical for determining disease outcome.

PMID- 9581798
TI  - Suppressed PHA activation of T lymphocytes in simulated microgravity is restored
      by direct activation of protein kinase C.
AB  - Utilizing clinostatic rotating wall vessel (RWV) bioreactors that simulate
      aspects of microgravity, we found phytohemagglutinin (PHA) responsiveness to be
      almost completely diminished. Activation marker expression was significantly
      reduced in RWV cultures. Furthermore, cytokine secretion profiles suggested that
      monocytes are not as adversely affected by simulated microgravity as T cells.
      Reduced cell-cell and cell-substratum interactions may play a role in the loss of
      PHA responsiveness because placing peripheral blood mononuclear cells (PBMC)
      within small collagen beads did partially restore PHA responsiveness. However,
      activation of purified T cells with cross-linked CD2/CD28 and CD3/CD28 antibody
      pairs was completely suppressed in the RWV, suggesting a defect in signal
      transduction. Activation of purified T cells with PMA and ionomycin was
      unaffected by RWV culture. Furthermore, sub-mitogenic doses of PMA alone but not
      ionomycin alone restored PHA responsiveness of PBMC in RWV culture. Thus our data
      indicate that during polyclonal activation the signaling pathways upstream of PKC
      activation are sensitive to simulated microgravity.

PMID- 9581799
TI  - Human neutrophils are devoid of the integral membrane protein caveolin.
AB  - The secretory vesicles of human neutrophils are rapidly mobilizable vesicles that
      contain several GPI-linked proteins, a characteristic feature of caveolae in
      other cells. To investigate whether secretory vesicles are structurally related
      to caveolae, we examined human neutrophils for the presence of caveolin, a major
      constituent of caveolae, by immunoblotting using monoclonal and polyclonal
      antibodies. Caveolin was not detected in lysates of human neutrophils nor in
      isolated plasma membrane/light membrane fractions in which secretory vesicles
      localize. In contrast, caveolin was readily detected in isolated membranes of
      adipose cells. We conclude that human neutrophils are devoid of caveolin and that
      secretory vesicles are not related to caveolae nor dependent on caveolae for
      mobilization.

PMID- 9581800
TI  - A novel cell surface proliferation-associated marker expressed on T cells and up
      regulated on germinal center B cells.
AB  - In this study we present data on a novel cell surface antigen recognized by
      monoclonal antibody (mAb) VPM30, originally thought to recognize only bovine and
      ovine sIg+ B cells from peripheral blood. Here we show that the antigen,
      molecular mass 28 kDa, is not only found in B cell follicles in frozen sections,
      but when used on paraffin sections VPM30 specifically stains B cells in the light
      zone of germinal centers but not in the mantle or dark zones. In addition we show
      that the antigen is also expressed by 90% of T cells after activation, with
      kinetics of antigen expression mirroring those of proliferation. By both size and
      distribution, the antigen appears to be novel, corresponding to no known cluster
      of differentiation, and will be of great use in the study of ruminant cellular
      immune responses.

PMID- 9581801
TI  - Role of the liver in T cell differentiation--generation of CD3-CD4+/CD8+TCRbeta-
      cells and CD3-4-8-TCRbeta+ cells from CD4-8-TCRbeta- athymic nude bone marrow
      cells by culture with parenchymal liver cells.
AB  - To investigate the influence of the liver on differentiation of hematopoietic
      stem cells/pro-T cells, TN-NWP-BMC (athymic nude bone marrow cells that were
      treated with anti-TCRbeta, anti-CD4, and anti-CD8 Abs plus complement and then
      passed through a nylon wool column) were cultured on parenchymal liver cells.
      After culture for 2.5 days, CD3-4-8-TCRbeta+ cells and CD3-CD4+/CD8+TCRbeta-
      cells were developed from TN-NWP-BMC. TCRVbeta8+ cells comprised 19.9% of CD3-4-8
      TCRbeta+ cells, and Vbeta8 mRNA was detected in the CD3-4-8-TCRbeta+ cells by
      reverse transcriptase-polymerase chain reaction. The CD3-CD4+/CD8+TCRbeta- cells
      contained not only single-positive cells but also CD4+8+ double-positive cells.
      The CD8 protein consisted of 88.9% CD8alpha+beta-, 10.1% CD8alpha+beta+, and 1%
      CD8alpha-beta+ molecules. From these results and the finding of co-expressed
      antigens, CD3-4-8-TCRbeta+ cells and CD3-CD4+/CD8+TCRbeta- cells appear to be
      immature cells not committed to a certain cell lineage.

PMID- 9581802
TI  - IL-8 is an essential mediator of the increased delayed-phase vascular
      permeability in LPS-induced rabbit pleurisy.
AB  - We investigated the involvement of IL-8 in the delayed vascular permeability (VP)
      in rabbit lipopolysaccharide (LPS)-pleurisy. Maximal level of interleukin-8 (IL
      8) was detected in pleural fluid at 2 h after LPS injection and anti-IL-8
      inhibited the delayed VP by 90%. Injection of homologous IL-8 induced VP, the
      time-course of which preceded that of LPS-induced delayed VP. Production of IL-8
      in LPS-pleurisy was inhibited with anti-tumor necrosis factor alpha (TNF-alpha),
      whereas the production of TNF-alpha was not affected with anti-IL-8. Injection of
      IL-8 did not induce TNF-alpha production and anti-TNF-alpha had no effect on IL-8
      induced VP. Injection of homologous TNF-alpha induced IL-8 production and VP, and
      TNF-alpha-induced delayed VP was blocked with anti-IL-8. These results indicate
      important roles of IL-8 in LPS-induced delayed VP and that TNF-alpha causes the
      delayed VP through the production of IL-8.

PMID- 9581803
TI  - Vasoactive intestinal peptide and pituitary adenylate cyclase-activating
      polypeptide modulate endotoxin-induced IL-6 production by murine peritoneal
      macrophages.
AB  - Vasoactive intestinal peptide (VIP) is a neuropeptide synthesized by immune cells
      that can modulate several immune aspects, including the function of cells
      involved in the inflammatory response, such as macrophages and monocytes.
      Production and release of cytokines by activated mononuclear phagocytes is an
      important event in the pathogenesis of ischemia-reperfusion injury. VIP has been
      shown to attenuate the deleterious consequences of this pathologic phenomenon. We
      have investigated the effects of VIP and PACAP38 on the production of interleukin
      6 (IL-6), a proinflammatory cytokine, by endotoxin-activated murine macrophages.
      Both neuropeptides exhibit a dual effect on the IL-6 production by peritoneal
      macrophages. Whereas VIP and PACAP inhibit with similar dose-response curves the
      release of IL-6 from macrophages stimulated with a LPS dose range from 100 pg/mL
      to 10 microg/mL, both neuropeptides enhance IL-6 secretion in unstimulated
      macrophages and in macrophages stimulated with very low LPS concentrations (1-10
      pg/mL). The inhibition on LPS-induced IL-6 production is specific, presumably
      mediated through a subtype of the PACAP-R. VIP and PACAP regulate the production
      of IL-6 at a transcriptional level. These results were correlated with an
      inhibition on both IL-6 expression and release in endotoxemic mice in vivo. These
      findings support the idea that in the absence of stimulation or in the presence
      of low doses of LPS, VIP and PACAP could play a role in immune system
      homeostasis. However, under toxicity conditions associated with high LPS doses,
      VIP and PACAP could act as protective mediators that regulate the excessive
      release of IL-6 in order to reduce inflammation or shock.

PMID- 9581804
TI  - Neuropeptide regulation of proinflammatory cytokine responses.
AB  - Severe traumatic injuries and infections are frequently accompanied by life
      threatening shock and are associated with increases in the proinflammatory
      cytokines, particularly tumor necrosis factor alpha (TNF-alpha). The body's first
      perception of injury is the nociceptive or pain response. This response is
      induced at the site of injury and is transmitted systemically by sensory
      neuropeptides, the tachykinins, released from sensory afferent c-fiber neurons.
      We studied the role of tachykinins in regulating the production of
      proinflammatory cytokines induced by the administration of bacterial
      lipopolysaccharide. Destruction of terminal sensory nerve endings before
      lipopolysaccharide administration abrogates tachykinin synthesis and down
      regulates TNF-alpha transcription and secretion. In contrast, the responses of
      interleukins-1 and -6 are unaffected. Pretreating animals with an antagonist for
      the substance P-specific NK-1 receptor also down-regulated the TNF-alpha
      response, whereas blockade of the NK-2 receptor had no effect. These findings
      indicate that substance P contributes to the induction of those cytokines that
      are involved in precipitating the shock response.

PMID- 9581805
TI  - Expression of macrophage-derived chemokine (MDC) mRNA in macrophages is enhanced
      by interleukin-1beta, tumor necrosis factor alpha, and lipopolysaccharide.
AB  - A cDNA encoding the C-C chemokine MDC was isolated from a human macrophage cDNA
      library by differential hybridization using monocyte- and macrophage-specific
      cDNA probes. During monocyte to macrophage differentiation in vitro, MDC
      expression is first detected after 1 day of culturing and reaches maximum levels
      after 6 days when macrophages have fully matured, as judged from the expression
      of known macrophage marker genes. Exposure of macrophages to lipopolysaccharide
      (LPS) results in a dose-dependent increase in MDC mRNA levels, with maximum
      induction occurring after 6-8 h, whereas expression levels of macrophage
      inflammatory protein-1alpha (MIP-1alpha), MIP-2, interleukin-1beta (IL-1beta),
      and tumor necrosis factor alpha (TNF-alpha) respond much faster to LPS.
      Furthermore, MDC expression in macrophages is enhanced by the inflammatory
      mediators TNF-alpha and IL-1beta. Similar to other TNF-alpha/IL-1beta-inducible
      genes, costimulation of macrophages with both cytokines leads to higher MDC
      expression levels than stimulation with a single cytokine. By contrast, both
      resting and activated monocytes do not express MDC mRNA.

PMID- 9581806
TI  - Arterial and venular endothelial cell costimulation of cytokine secretion by
      human T cell clones.
AB  - Vascular endothelial cell (EC) costimulation of cytokine secretion by T
      lymphocytes may be important in inflammation and allograft rejection. Venous and
      arterial iliac endothelial cells (VIEC, AIEC) both costimulate interleukin-2 (IL
      2) production by peripheral blood lymphocytes (PBL) or T cell clones stimulated
      with phytohemagglutinin (PHA). Interferon-gamma (IFN-gamma) production is
      costimulated in a subset of clones but IL-4 is not. Surprisingly, two T cell
      clones were reciprocally better costimulated by VIEC or AIEC. EC activation by
      pretreatment with tumor necrosis factor alpha (TNF-alpha) does not increase T
      cell costimulation despite large increases in EC cell adhesion molecule
      expression. Neither VIEC nor AIEC express CTLA4-binding molecules and
      costimulation is blocked by cyclosporin A, suggesting that CD28 is not involved
      in EC costimulation of T cells. These data suggest that adult vascular EC
      costimulate production of IL-2 and IFN-gamma but not IL-4 by mature T cells, that
      EC costimulation is not increased in inflamed tissues, and that different EC
      optimally costimulate particular T cells. These findings have implications for
      the nature of the costimulatory signal(s) provided by EC and may be important in
      understanding vasculitis or atherosclerosis.

PMID- 9581807
TI  - Interleukin-2-induces development of denditric cells from cord blood CD34+ cells.
AB  - Dendritic cells (DC) have been shown to develop along a myeloid or lymphoid
      lineage of differentiation propagated from bone marrow or early thymic precursor
      cells with hematopoietic cytokines. In our study, we have induced growth and
      differentiation of DC from cord blood CD34+ cells initiated in interleukin-2 (IL
      2) alone or in IL-2 + stem cell factor (SCF) + tumor necrosis factor alpha (TNF
      alpha)-supplemented medium and cultured with IL-2 or IL-2 + SCF for 28-35 days.
      Dendritic morphology and antigenic phenotype of DC grown with IL-2 were
      characteristic for DC cultured in the presence of granulocyte-macrophage colony
      stimulating factor (GM-CSF). Growth and differentiation of DC was followed by an
      increase in expression of MHC II and co-stimulating molecules CD80 and CD86. We
      have also shown the expression of the IL-2 receptor (IL-2R) gamma-chain in CD34+
      cells after 2-3 days of culture with IL-2 alone. The co-expression of the IL-2R
      alpha, beta, and gamma subunits in both DC cultured with IL-2- or GM-CSF
      containing cocktail of cytokines was also shown. The time curve for induction of
      IL-2R demonstrated low levels of subunit expression at the beginning of culture.
      The number of CD1a cells co-expressing CD25, CD122, and CDgamma increased to
      about 24-68 and to 78-95% after 21 and 28-35 days, respectively. Development of
      natural killer cells was shown along with DC. The proportion of CD56+ cells and
      cytotoxicity increased in a time-dependent manner.

PMID- 9581808
TI  - Inhibition of p130cas tyrosine phosphorylation by calyculin A.
AB  - P130cas is a dominant tyrosine phosphorylated protein in v-src-and v-crk
      transformed cells. Tyrosine phosphorylation also occurs in response to integrin
      mediated cell adhesion. P130cas has a unique structure with multiple SH2 and SH3
      binding sites, which makes it a candidate docking protein that might be involved
      in several signal transduction pathways. Little is known about how p130cas itself
      is regulated. In this report we present evidence that tyrosine phosphorylated
      p130cas was rapidly dephosphorylated in several lymphatic cell lines after
      treatment with calyculin A, a serine/threonine phosphatase inhibitor. A similar
      result was obtained with okadaic acid, but higher concentrations and longer
      incubation times were required. Constitutive phosphorylation as well as receptor
      cross linking-induced p130cas phosphorylation was inhibited. Furthermore, the
      p130cas-Crk association was disrupted by treatment of cells with calyculin A.
      However, the p130cas-Lyn association was not affected. These results suggest that
      calyculin A specifically affects SH2 domain-mediated protein-protein interactions
      and that Lyn does not bind to a susceptible SH2 domain. Furthermore, the data
      presented is consistent with the existence of a calyculin A-sensitive phosphatase
      or tyrosine kinase that may be a critical regulator of p130cas tyrosine
      phosphorylation.

PMID- 9581809
TI  - IgA Fc receptor (CD89) activation enables coupling to syk and Btk tyrosine kinase
      pathways: differential signaling after IFN-gamma or phorbol ester stimulation.
AB  - IgA Fc receptors (Fc alphaR) can mediate a variety of inflammatory responses. It
      has been demonstrated that the FcRgamma subunit is critical in mediating
      signaling through Fc alphaR. We show that aggregation of Fc alphaR on U937 cells
      and blood neutrophils results in tyrosine phosphorylation of several
      intracellular proteins, including the FcR gamma subunit, p72syk, and Bruton
      tyrosine kinase (Btk). Syk was found to be associated with Fc alphaR and its
      phosphorylation was increased in phorbol myristate acetate (PMA)- and interferon
      gamma (IFN-gamma)-treated U937 cells. In contrast, phosphorylation of Btk was
      only detected after cell treatment with PMA but not IFN-gamma. These data
      indicate that signaling through Fc alphaR gamma2 involves at least two
      subfamilies of tyrosine kinases, syk and Btk. Our results also suggest that
      activation of tyrosine kinase pathways through Fc alphaR depends on the
      activation state of the cell. This may be an important regulatory mechanism in
      IgA-mediated responses at inflammatory sites.

PMID- 9581810
TI  - Granulosa cell tumors express erbB4 and are sensitive to the cytotoxic action of
      heregulin-beta2/PE40.
AB  - The molecular genetic events involved in the etiology of human granulosa cell
      (GC) tumors, which represent approximately 7% of all malignant ovarian neoplasms,
      are unknown. Amplification and/or overexpression of the ERBB genes are a feature
      of many cancer types, and overexpression of erbB2 correlates with poor prognosis
      in epithelial ovarian cancer. In the present study, we used immunohistochemistry
      to determine the level and frequency of expression of different erbB receptors in
      GC tumors. Ten of 12 tumors expressed erbB4 at moderate to high levels in >50% of
      cancer cells, whereas erbB2 (6 of 12) and erbB3 (2 of 12) were expressed less
      frequently. Western blot experiments showed that the only available GC tumor cell
      line, COV434, also expressed erbB receptors. Heregulin (HRG)-beta2, a ligand for
      erbB3 and erbB4 receptors, stimulated tyrosine phosphorylation of the erbB
      receptors, which was accompanied by activation of Erk1 and Erk2, two mitogen
      activated protein kinases with a functional role in mitogenesis. Importantly, HRG
      increased cell proliferation in COV434 cells, and treatment with HRG/PE40, a
      ligand toxin shown previously to be cytotoxic against human breast cancer cells
      overexpressing erbB receptors, led to a dramatic and irreversible decrease in
      cell number. These results indicate that erbB receptor signaling pathways may be
      critical in the control of GC tumor cell proliferation and that HRG/PE40 is a
      potential therapeutic agent for the treatment of GC tumors.

PMID- 9581811
TI  - Direct evidence that apoptosis enhances tumor responses to fractionated
      radiotherapy.
AB  - Currently, the contribution of cellular apoptotic sensitivity to tumor response
      after radiation therapy remains controversial. To address this issue, the
      survival of Rat-1 fibroblasts containing a 4-hydroxytamoxifen-regulated c-Myc
      allele, c-MycER (T. D. Littlewood et al., Nucleic Acids Res., 23: 1686-1690,
      1995), after single and fractionated doses of radiation was investigated. This
      model system allows pharmacological regulation of apoptosis sensitivity in the
      same cells in vitro and as xenograft tumors derived from these cells in vivo (G.
      I. Evan et al., Cell, 69: 119-128, 1992; R. M. Alarcon et al., Cancer Res., 56:
      4315-4319, 1996). Activating c-MycER in vitro resulted in marked sensitization of
      Rat-1 fibroblasts to the effects of both single-dose and fractionated irradiation
      as measured by the induction of apoptosis and clonogenic survival. Overexpression
      of the antiapoptosis protein Bcl-2 suppressed the induction of apoptosis and
      increased clonogenic survival in cells with activated c-Myc after single-dose and
      fractionated radiation. Systemic time-release implant delivery of 4
      hydroxytamoxifen to severe combined immunodeficient mice bearing Rat-1-MycER
      tumors over the course of either single-dose (10 Gy) or fractionated (five
      fractions of 2 Gy) radiotherapy resulted in prolonged tumor growth delay relative
      to identical tumors from mice that received placebo implants. Furthermore, tumors
      derived from Rat-1-MycER cells that overexpressed Bcl-2 exhibited shorter tumor
      growth delays relative to similarly treated Rat-1-MycER tumors. The length of
      tumor growth delay after single-dose or fractionated radiotherapy strongly
      correlated with the extent of radiation-induced apoptosis in the xenograft tumors
      as measured by terminal deoxynucleotidyl transferase-mediated nick end labeling.
      These in vivo results provide direct evidence that increasing the sensitivity of
      tumor cells to die by apoptosis increases the efficacy of fractionated
      radiotherapy by reducing tumor cell clonogenic survival.

PMID- 9581812
TI  - Involvement of nitric oxide during phthalocyanine (Pc4) photodynamic therapy
      mediated apoptosis.
AB  - Photodynamic therapy (PDT), a new treatment modality, uses a combination of
      photosensitizing agent and visible light for the therapy of many solid
      malignancies. The hallmark of PDT is intracellular oxidative stress mediated by
      reactive oxygen species, which, through a cascade of events, results in a cell
      kill that induces apoptosis in some cells. To better understand the mechanism of
      apoptosis, we hypothesized the role of nitric oxide (NO), which is considered to
      be involved in a variety of physiological and pathological processes, during PDT.
      The model photosensitizer we have been working with is a silicon-phthalocyanine
      compound termed Pc4. Here, we investigated the involvement of NO during Pc4 PDT
      in PDT of apoptosis-resistant radiation-induced fibrosarcoma (RIF-1) cells and in
      PDT of apoptosis-sensitive human epidermoid carcinoma (A431) cells. Pc4 PDT
      resulted in a rapid increase in nitrite production in A431 cells, starting as
      early as 15 s post-PDT, and showed a progressive increase up to 15 min post-PDT.
      This increase in nitrite production was observed in cell lysates as well as in
      the cell culture medium. RIF-1 cells did not show an increase in nitrite
      production in either the cell lysates or the culture medium. At this time, a
      majority of the cells were viable. The Western blot analysis also showed a rapid
      increase in the expression of the constitutive form of NO synthase as early as 15
      s post-PDT when compared to that of the controls. This response showed a dose
      dependency up to 5 min after Pc4 PDT. This observation was confirmed by a [3H]L
      citrulline assay, which also showed a similar pattern for constitutive NO
      synthase activity. RIF-1 cells did not show any change in protein expression or
      enzyme activity after the same treatment. These data, for the first time,
      demonstrate the generation of NO during PDT and suggest that it may be involved
      in PDT-mediated apoptosis. This may have relevance in improving the therapeutic
      efficacy of PDT using pharmacological modulators of NO or NO synthase.

PMID- 9581813
TI  - Potentiation of chlorambucil cytotoxicity in B-cell chronic lymphocytic leukemia
      by inhibition of DNA-dependent protein kinase activity using wortmannin.
AB  - In this study, we examined the ability of wortmannin to modulate chlorambucil
      (CLB) cytotoxicity in lymphocyte samples from patients with B-cell chronic
      lymphocytic leukemia (B-CLL). It has been suggested previously that enhanced
      cross-link repair is a primary mechanism of resistance to nitrogen mustards (NMs)
      in B-CLL. DNA-dependent protein kinase (DNA-PK) is involved in the repair of
      double-strand breaks and in rejoining steps in recombination mechanisms. Mutants
      defective in this process are hypersensitive to alkylating agents. We have
      recently demonstrated that the activity of DNA-PK is a determinant in the
      cellular response of B-CLL to CLB. The DNA-PK gene has homology to the P110
      phosphatidylinositol 3-kinase (PI 3-K). Wortmannin, an inhibitor of P110 PI 3-K,
      also inhibits DNA-PK activity in vitro. We investigated the effect of wortmannin
      on DNA-PK activity and CLB toxicity in the lymphocytes from 11 patients with B
      CLL. Our results demonstrate that DNA-PK activity is decreased after exposure to
      wortmannin in a dose-dependent manner. Wortmannin, at nontoxic concentrations,
      synergistically sensitized B-CLL lymphocytes to the effects of CLB. Moreover, we
      observed a significant correlation when we compared the fold decrease in DNA-PK
      activity and the synergistic value (I), obtained when wortmannin was used at 0.1
      microM. In the resistant B-CLL lymphocyte samples, there was a highly significant
      correlation between the ability of wortmannin at 0.1 and 0.25 microM to decrease
      the level of DNA-PK activity and to increase CLB sensitivity. In a model of
      primary human tumor cells, our findings suggest that the inhibition of DNA-PK
      activity may be a powerful way to overcome resistance to NMs such as CLB and
      point to new possibilities to improve the effectiveness of NM therapy.

PMID- 9581814
TI  - Selective sensitivity to radiation of cerebral glioblastomas harboring p53
      mutations.
AB  - Recent studies suggest that a balance may exist between the cell cycle arrest and
      apoptosis-inducing functions of the p53 tumor suppressor gene. Adenoviral p21
      transduction attenuates apoptosis, whereas deletion of the p21 gene promotes it,
      and p21-null xenografts respond better than isogenic p21-wild type tumors to
      irradiation. Hence, the role of p53 in dictating the clinical response to
      radiotherapy and chemotherapy may be more complex than previously thought. We
      have analyzed survival and radiation response (regrowth-free period) of 42
      patients with glioblastomas whose p53 status was determined by a sensitive yeast
      functional assay. Multivariate analysis revealed that p53 mutation is associated
      with longer survival (P < 0.02). Among 36 radiation-treated patients, the
      regrowth-free period after treatment was significantly longer for tumors with p53
      mutations (P < 0.0001), and p53 mutation was the sole independent factor
      predictive of radiotherapeutic response (P < 0.01). Survival time after regrowth
      was independent of p53 status, suggesting that the difference in survival was
      related to the treatment rather than to the intrinsic aggressiveness of the
      tumor. Thus, in this Northern Japanese population, p53 mutation is a marker for
      better radiation response in glioblastomas, and this results in significantly
      longer survival.

PMID- 9581815
TI  - Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and
      primitive neuroectodermal tumors of the central nervous system.
AB  - About one-third of sporadic basal cell carcinomas (BCCs) of the skin and 10-15%
      of primitive neuroectodermal tumors (PNETs) of the central nervous system show
      mutations in the PTCH tumor suppressor gene. The PTCH gene product (Ptch)
      functions as a transmembrane receptor for the Sonic hedgehog protein (Shh) and
      interacts with another transmembrane protein called Smoh. To further elucidate
      the significance of alterations in the Shh signaling pathway, we investigated 31
      sporadic BCCs and 15 PNETs for the mutation and/or expression of SMOH, PTCH, SHH,
      and GL11. In addition, we fine-mapped the SMOH gene locus by fluorescence in situ
      hybridization to chromosomal band 7q32. Mutational analysis identified four BCCs
      with somatic missense mutations in SMOH affecting codon 535 (TGG==>TTG:
      Trp==>Leu) in three tumors and codon 199 (CGG==>TGG: Arg==>Trp) in one tumor. A
      missense mutation at codon 533 (AGC==>AAC: Ser==>Asn) was found in one PNET. PTCH
      mutations were detected in eight BCCs and one PNET. Two BCCs demonstrated
      mutations in both SMOH and PTCH. The majority of tumors showed an increased
      expression of SMOH, PTCH, and GL11 transcripts as compared with that of normal
      skin and nonneoplastic brain tissue, respectively. In contrast, only one BCC and
      one PNET expressed SHH mRNA at levels detectable by reverse transcription-PCR,
      and no SHH gene mutations were found. In summary, our results indicate that both
      PTCH and SMOH represent important targets for genetic alterations in sporadic
      BCCs and PNETs.

PMID- 9581816
TI  - Chromosome 3p14 alterations in lung cancer: evidence that FHIT exon deletion is a
      target of tobacco carcinogens and asbestos.
AB  - Alterations in the FHIT gene region have been previously associated with smoking
      status and the occurrence of lung tumors. In the current study, we examined the
      nature of the mutations that occur at FHIT and the types of carcinogen exposures
      that are associated with FHIT alterations. We screened 40 primary lung tumors for
      the presence of point mutations within the coding exons of FHIT using PCR-single
      strand conformational polymorphism. Tumors were also analyzed for allelic loss
      using microsatellite markers located in or near FHIT. No tumors contained point
      mutations within the coding region of the FHIT gene. However, several samples
      failed to generate a PCR product, suggesting that regions of the gene are
      homozygously deleted. Samples were reanalyzed for exon loss using PCR; 13 of 30
      tumors failed to generate a PCR product, and 20 of 30 tumors were missing at
      least one FHIT exon or had loss (loss of heterozygosity or deletion) of one
      microsatellite marker, suggesting that regions of the gene are homozygously
      deleted. These data indicate that the FHIT gene has a novel pattern of mutational
      inactivation not seen previously with other tumor suppressor genes, most likely
      influenced by the proximity of the FRA3B region. There were no associations of
      age, sex, p53, or k-ras mutation and FHIT exon deletion. However, there was an
      association of smoking duration and asbestos exposure with FHIT exon loss,
      indicating that carcinogenic exposures may be causal in the generation of
      alterations in the FHIT region.

PMID- 9581817
TI  - Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell
      apoptosis and p53 accumulation in gastric carcinomas.
AB  - A novel inhibitor of apoptosis designated survivin has recently been found in
      many common human cancers but not in normal tissues. A potential distribution of
      survivin in gastric cancer and its implication for apoptosis inhibition have been
      investigated. Recombinant survivin expressed in Escherichia coli as a glutathione
      S-transferase fusion protein was used to raise a novel panel of mouse monoclonal
      antibodies. In an immunohistochemical analysis of 174 cases of gastric carcinomas
      (stages I-III), anti-survivin monoclonal antibody 8E2 (IgG1) reacted with 34.5%
      of cases (60 of 174 cases) with a variable number of tumor cells stained (20
      100%). In contrast, no expression of survivin in neighboring normal tissues was
      observed. When stratified for p53 and bcl-2 expression and apoptotic index, the
      expression of survivin significantly segregated with p53- and bcl-2-positive
      cases [56.1 versus 15.2% (P = 0.001) and 69.2 versus 31.6% (P = 0.006),
      respectively] and with a decreased apoptotic index as compared with that of
      survivin-negative tumors (0.97 +/- 0.64 versus 0.62 +/- 0.39%, P < 0.001). These
      data identify a role for survivin in promoting aberrantly increased cell
      viability in gastric cancer and suggest a potential correlation between
      accumulated p53 and survivin expression in neoplasia.

PMID- 9581818
TI  - Transactivation of transforming growth factor alpha gene by hepatitis B virus
      preS1.
AB  - Hepatitis B virus (HBV) causes acute and chronic liver injury, and integration of
      HBV DNA is considered to be an important pathogenic determinant for
      hepatocarcinogenesis and tumor development. Transforming growth factor alpha (TGF
      alpha) drastically accelerates hepatocarcinogenesis when it is overexpressed in
      TGF-alpha transgenic mice (C. Jhappan et al., Cell, 61: 1137-1146, 1990). In HBV
      infected patients, hepatocellular carcinoma (HCC) cells show elevated expression
      of TGF-alpha (C. C. Hsia et al., J. Med. Virol., 43: 216-221, 1994), the
      mechanism for which, however, has not been clarified yet. We here show that
      preS1, a part of the HBV large surface protein, carries a transcriptional
      transactivation domain and activates the transcription of the TGF-alpha gene by 2
      fold in human HCC HuH6 cells. The responsive elements are restricted to the 315
      bp segment of the proximal TGF-alpha promoter (-373 to -59). Furthermore, the
      expression of TGF-alpha was markedly increased in permanently preS1-producing
      HuH6 transformants. The crucial role for HBV preS1 in hepatocarcinogenesis and
      tumor development through transactivation of the TGF-alpha gene may give us new
      insight into the understanding of pathogenesis and therapy of viral
      hepatocarcinogenesis.

PMID- 9581820
TI  - Correlation of high-resolution magic angle spinning proton magnetic resonance
      spectroscopy with histopathology of intact human brain tumor specimens.
AB  - High-resolution magic angle spinning proton (HRMAS 1H) magnetic resonance
      spectroscopy produces well-resolved spectra of metabolites from intact tissue
      specimens. Here we report the results of a preliminary study of 19 human brain
      tumors obtained by applying this method. Among these 19 cases were 2 low-grade
      astrocytomas, 1 anaplastic astrocytoma, 8 glioblastomas, 6 meningiomas, and 2
      schwannomas. In addition, autopsy human brain tissues from two subjects without
      any known neurological diseases were used as normal controls. The HRMAS 1H
      magnetic resonance spectroscopy measurements were performed at 2 degrees C on a
      400-MHz NMR spectrometer with a HRMAS speed of 2.5 kHz. From these HRMAS 1H MR
      spectra, we measured the concentrations of 11 metabolites, the ratios of 15
      metabolites (resonances) to creatine (at 3.03 ppm), and the spin-spin relaxation
      time for these metabolites (resonances). Our results indicate that these
      parameters have the potential to characterize tumor types and grades with
      statistical significance as well as identify tumor biochemical characteristics.
      In particular, we found that compared with metabolite concentrations and
      metabolite spin-spin relaxation time, the metabolic ratios presented the highest
      sensitivity in differentiating normal tissue from tumors, as well as in
      distinguishing between tumor groups. Of 15 analyzed metabolic ratios, 12 showed
      statistical significance in differentiating normal tissue from low-grade and
      anaplastic astrocytomas, 13 showed statistical significance in differentiating
      normal tissue from glioblastomas, 14 showed statistical significance in
      differentiating normal tissue from schwannomas, and 9 showed statistical
      significance in differentiating normal tissue from meningiomas. Moreover, our
      results strongly indicate that the resonance ratio of inositol (at 4.05 ppm) to
      creatine may help distinguish tumor type. Our results suggest that the HRMAS
      method for intact tissue measurement may function as an adjunct to histopathology
      and contribute to improved accuracy for brain tumor diagnoses.

PMID- 9581819
TI  - 1Alpha,25-dihydroxyvitamin D3 inhibits programmed cell death in HL-60 cells by
      activation of sphingosine kinase.
AB  - Sphingolipid breakdown products [ceramide, sphingosine, and sphingosine-1
      phosphate (SPP)] are emerging as a new class of bioactive molecules. In agreement
      with previous studies, treatment of human promyelocytic leukemia HL-60 cells with
      1-alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] induced a transient increase of
      ceramide levels within 2 h, which then returned to basal levels within 8 h. In
      contrast, sphingosine kinase activity increased more slowly and reached maximal
      levels only after 20 h of exposure, leading to a concomitant increase in SPP
      level. Unlike treatments with cell-permeable ceramide analogues or
      sphingomyelinase, which induce apoptosis, 1,25-(OH)2D3 did not induce apoptosis,
      despite the early formation of ceramide. Moreover, prolonged treatment of HL-60
      cells with 1,25-(OH)2D3 suppressed ceramide-induced apoptosis. There was a
      correlation between the time course and dose response of the activation of
      sphingosine kinase by 1,25-(OH)2D3 and the protection against apoptosis. In
      contrast, treatment with all-trans-retinoic acid neither stimulated sphingosine
      kinase activity nor protected cells from ceramide-induced apoptosis. Treatment
      with SPP protected HL-60 cells from ceramide-induced apoptosis, and N,N
      dimethylsphingosine (DMS), a competitive inhibitor of sphingosine kinase,
      prevented the survival effect of 1,25-(OH)2D3. The effect of DMS was counteracted
      by SPP, suggesting that SPP is a critical component of the cytoprotective effect
      of 1,25-(OH)2D3. Chelerythrine chloride, an inhibitor of protein kinase C,
      markedly reduced sphingosine kinase activity and the apoptosis-sparing effect of
      1,25-(OH)2D3, and conversely, the tumor promoter 12-O-tetradecanoylphorhol-13
      acetate not only suppressed ceramide-induced apoptosis but also stimulated
      sphingosine kinase activity. Moreover, the protective effect of 12-O
      tetradecanoylphorbol-13-acetate was blocked by DMS. Collectively, our
      observations indicate that the cytoprotective effect of 1,25-(OH)2D3 is mediated
      by SPP, which is formed as a consequence of activation of sphingosine kinase.

PMID- 9581821
TI  - Establishment of a Salmonella tester strain highly sensitive to mutagenic
      heterocyclic amines.
AB  - Heterocyclic amines (HCAs) that are present in cooked foods require metabolic
      activation to exert their genotoxicity. They undergo activation via N
      hydroxylation by cytochrome P450 1A2 (CYP1A2), followed by O-esterification by O
      acetyltransferase (OAT). To develop a Salmonella tester strain that is highly
      sensitive to mutagenic HCAs, we introduced a coexpression plasmid (p1A2OR)
      carrying human CYP1A2 and NADPH-CYP reductase cDNAs and an expression plasmid
      (pOAT) carrying Salmonella OAT to Salmonella typhimurium TA1538 to yield a
      TA1538/ARO strain. The TA1538/ARO strain was proven to express the enzymes, as
      indicated by high activities of 7-ethoxyresorufin O-deethylase and isoniazid N
      acetylase. The TA1538/ARO strain exhibited very high sensitivity to mutagenic
      HCAs 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and a
      somewhat higher sensitivity to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      compared with the parent Ames tester strain TA1538. The minimum concentrations of
      2-amino-3,4-dimethylimidazo[4,5-f]quinoline, IQ, 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine giving
      positive results were defined by evidence that the number of colonies increased
      in a dose-dependent manner and reached a number two times higher than that
      obtained by vehicle alone as a control in the TA1538/ARO strain at concentrations
      of 0.3, 3, 30, and 1000 pM, respectively. When the membrane and cytosol fractions
      prepared from TA1538/ARO were added to a mixture containing the parental TA1538,
      the sensitivity of TA1538 to IQ was much lower than that seen with TA1538/ARO.
      These results indicate that the intracellular expression of drug-metabolizing
      enzymes makes the established strain of Salmonella highly sensitive to mutagenic
      HCAs.

PMID- 9581822
TI  - BRCA-associated breast cancer: absence of a characteristic immunophenotype.
AB  - To characterize the biological features of breast cancer associated with germ
      line mutations in BRCA1 and BRCA2, invasive tumors were studied from 58 Jewish
      women ascertained through studies of early-onset breast cancer. All women were
      tested for the BRCA1 founder mutations 187delAG (commonly known as 185delAG) and
      5385insC (commonly known as 5382insC) and the BRCA2 founder mutation 6174delT.
      Mutations were detected in 17 of 58 (29.3%) women. Comparing BRCA-associated
      breast cancers (BABCs) to cases arising in women without founder mutations, no
      differences were noted in tumor size, tumor stage, or frequency of axillary nodal
      involvement. Infiltrating ductal carcinoma was the predominant histological type
      in both groups. BABCs were significantly more likely to be of histological grade
      III (100 versus 63%; P = 0.04), estrogen receptor negative (75 versus 35%; P =
      0.004), and HER2/neu negative (87 versus 58%; P = 0.04). An associated
      intraductal component was present in 59% of BABCs and 76% of cancers not
      associated with mutations (P = not significant). A high Ki-67 labeling index was
      more commonly observed in BABCs than in cases without mutations (83 versus 48%; P
      = 0.09). There were no differences between the two groups in the frequency of
      expression of epidermal growth factor receptor, cathepsin D, bcl-2, p27, p53, or
      cyclin D. There were no significant differences in relapse-free or overall
      survival. These observations suggest that breast cancers arising in Jewish women
      with germ-line BRCA founder mutations have a greater proliferative potential than
      cancers in women without such mutations. Additional studies of BABC are required
      to determine the nature and implications of additional genetic abnormalities
      occurring in these tumors.

PMID- 9581823
TI  - The level of urokinase-type plasminogen activator receptor is increased in serum
      of ovarian cancer patients.
AB  - Ascites and serum of patients with ovarian carcinoma contain a soluble form of
      urokinase-type plasminogen activator receptor (uPAR). We now report that pro-uPA
      Sepharose-purified uPAR from ascites of patients with ovarian carcinoma is the
      full-length molecule missing the glycosyl-phosphatidylinositol anchor, as
      determined by its amino acid composition. We next examined the significance of
      determining serum soluble uPAR (suPAR) levels in ovarian cancer patients using a
      specific ELISA and compared the results with serum concentrations of CA-125, an
      established diagnostic marker. Serum from pre- and postoperative ovarian cancer
      patients was assayed for suPAR and CA-125. The majority of the patients with
      ovarian cancer had enhanced preoperative serum levels of suPAR compared with
      healthy controls, but suPAR concentrations decreased after operation. Although
      uPAR was associated with most ovarian carcinomas, it appeared to be a less
      specific indicator for ovarian cancer than CA-125. On the other hand, suPAR was
      more specific for other types of solid tumors. Moreover, we have observed some
      cases of ovarian cancer that showed increase of suPAR but not of CA-125. The
      prognostic significance of serum suPAR assay for survival of ovarian carcinoma
      patients was evaluated using Cox's proportional hazards analysis. Our preliminary
      data show that high preoperative levels of suPAR were associated with worse
      survival of the patients, whereas CA-125 had no prognostic implications. This is
      the first report evaluating the assay of serum suPAR levels in ovarian cancer and
      analyzing its value as a tumor or prognostic marker.

PMID- 9581824
TI  - Somatostatin receptor subtype specificity and in vivo binding of a novel tumor
      tracer, 99mTc-P829.
AB  - Recent data suggest that somatostatin receptors (SSTRs) are expressed on various
      tumor cells. High-level expression of SSTR on the tumor cell surface provides the
      basis for the successful clinical use of radiolabeled ligands for the in vivo
      localization of tumor sites. We have characterized the in vitro binding
      properties of the novel SSTR ligand 99mTc-P829 using primary human tumors
      (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small
      cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell
      lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3,
      4, and 5. 99mTc-P829 bound to primary tumor cells and tumor cell lines with high
      affinity and high capacity. The dissociation constants (Kd) ranged between 1 and
      20 nM. 99mTc-P829 also bound with high affinity to the transfected hSSTR2 (Kd,
      2.5 nM), hSSTR5 (Kd, 2 nM), and hSSTR3 (Kd, 1.5 nM). Binding of 99mTc-P829 to
      hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and
      vasoactive intestinal peptide (VIP; IC50, 2 nM) and, less effectively, by Tyr3
      octreotide (IC50, 20 nM). In contrast, the binding of 99mTc-P829 to hSSTR2 and
      hSSTR5 could be displaced by P829/([ReO]-P829) and Tyr3-octreotide but not by
      VIP. 99mTc-P829 scintigraphy revealed in vivo binding to primary or metastatic
      tumor sites in seven of eight patients with breast cancer and six of six patients
      with melanoma. In summary, our data show that 99mTc-P829 binds with high affinity
      to many different types of primary and cloned tumor cells. Furthermore, our data
      identify hSSTR2, the VIP acceptor hSSTR3, and hSSTR5 as the respective target
      receptors. Because these receptors are frequently expressed at high levels on
      primary tumor cells, 99mTc-P829 appears to be a promising novel peptide tracer
      for tumor imaging.

PMID- 9581825
TI  - Selective down-regulation of progesterone receptor isoform B in poorly
      differentiated human endometrial cancer cells: implications for unopposed
      estrogen action.
AB  - The uterine endometrium responds to unopposed estrogen stimulation with rapid
      cell proliferation. Progesterone protects the endometrium against the
      hyperplastic effects of estradiol (E2) through progesterone receptors (PRs), of
      which two isoforms are expressed: human (h) PRA and PRB. hPRB has a longer NH2
      terminus and may function differently from hPRA. Thus, the relative expression of
      hPRA:hPRB is likely to be important for the action of progesterone. We
      hypothesized that the hPRA:hPRB ratios may be abnormal in endometrial cancer,
      leading to a lack of normal progesterone protection against the growth-promoting
      effects of E2. To test this hypothesis, well-differentiated Ishikawa endometrial
      cancer cells were compared to poorly differentiated Hec50 and KLE cells. Reverse
      transcription-PCR was chosen as a sensitive method to detect transcripts for the
      two forms of PR. The relative expression of PR isoforms under hormonal
      stimulation was determined by Western blotting. Transient transfections of hPRA
      and hPRB into endometrial cells allowed the evaluation of the transcriptional
      activity of each isoform independently on reporter gene transcription under the
      control of a simple progesterone response element-containing promoter. The effect
      of coexpressing the estrogen receptor on PR expression was also studied. Ishikawa
      cells (well-differentiated) express both hPRA and hPRB. Both isoforms, but
      predominantly hPRB, are up-regulated by E2 and not by tamoxifen or the pure
      antiestrogen ICI 182,780. Hec50 and KLE cells (poorly differentiated) express
      only hPRA. No hPRB is present in the poorly differentiated cells, and it is not
      induced by estrogen receptor expression and/or estrogen treatment. In all cells,
      hPRB expression, whether endogenous or produced as a result of transfection, acts
      as a stronger transcription factor than hPRA on a simple progesterone-dependent
      promoter. We speculate that down-regulation of hPRB may predict for poorly
      differentiated endometrial cancers that do not respond to progestin therapy.

PMID- 9581826
TI  - Expression of all known vasopressin receptor subtypes by small cell tumors
      implies a multifaceted role for this neuropeptide.
AB  - Vasopressin is one of several small neuropeptides that are reported to be
      autocrine growth factors for small cell carcinoma of the lung (SCCL). It has been
      assumed that this peptide exercises its mitogenic influences through the
      vasopressin V1a receptor, and we have previously demonstrated that this receptor
      is expressed by classical and variant SCCL. Activation of the vasopressin V1a
      receptor produces changes in phospholipases C, D, and A2, in protein kinase C,
      and in Ca2+ mobilization. This study demonstrates that SCCL cells express not
      only vasopressin V1a receptors but also mRNAs and proteins representing normal
      V1b receptors and V2 receptors. They were also shown to express mRNA for a human
      form of the putative receptor rabbit vasopressin-activated calcium-mobilizing
      receptor (VACM-1). Additionally, SCCL tumor cells were found to express mRNA and
      protein representing a possible nonfunctional, shortened, "diabetic" form of the
      vasopressin V2 receptor that is the product of incomplete posttranscriptional
      splicing. At least four of these five vasopressin receptors were produced by cell
      lines exemplifying classical and variant forms of SCCL. No differences in the
      sequences for the V1 receptors between classical and variant SCCL were found.
      However, although the nature and expression of both vasopressin V1 receptors and
      human VACM are apparently unaffected by dedifferentiation in SCCL, only the
      abnormal (and probably nonfunctional) form of the V2 receptor could be
      demonstrated in variant cell line NCI H82. Functional engagement of vasopressin
      V2 receptors is reported to produce rises in cAMP and activation of protein
      kinase A, whereas stimulation of V1b receptors is believed to produce similar
      changes to those produced by V1a receptors, i.e., activation of phospholipases
      and of protein kinase C. Stimulation of VACM receptors raises intracellular free
      Ca2+ through currently unknown but phosphoinositide-independent mechanisms. The
      presence of all known vasopressin receptors that are, together, potentially
      capable of inducing several different transduction cascades in small cell tumor
      cells suggests that this peptide serves a multifaceted role in tumor physiology.

PMID- 9581827
TI  - The key to the antiestrogenic mechanism of raloxifene is amino acid 351
      (aspartate) in the estrogen receptor.
AB  - The crystallization of the ligand-binding domain (LBD) of the estrogen receptor
      (ER) with 17beta-estradiol and raloxifene [A. M. Brzozowski et al., Nature
      (Lond.), 389: 753-758, 1997] now provides a molecular basis for the biological
      activity of complexes as either agonists or antagonists. It is well established
      that the critical structural feature of antiestrogens is a correctly positioned
      alkylaminoethoxy side chain. The X-ray crystallography clearly shows that the
      alkylaminoethoxy side chain of raloxifene causes a specific and inappropriate
      molecular perturbation of the LBD and that the nitrogen in the side chain must
      hydrogen bond with aspartate 351 in the LBD of ER. We previously identified and
      characterized a naturally occurring mutation in the ER from a tamoxifen
      stimulated transplantable human breast tumor line. The mutation is at AA351 of
      LBD, where the aspartate is changed to tyrosine (Asp351Tyr). In this report, we
      compared and contrasted the pharmacology of raloxifene to block or induce E2
      stimulated increase in TGF-alpha mRNA in stable transfectants of ER-negative
      human breast cancer cells with the cDNAs from wild-type, mutant-amino acid (AA)
      400 ER and mutant-AA 351 ER. Our results show that the mutation at AA 351 that
      replaces aspartate by tyrosine specifically changes the pharmacology of
      raloxifene from an antiestrogen to an estrogen. By contrast, a mutation at AA 400
      does not, and the antiestrogenic properties of raloxifene are retained. These
      data and the fact that the nitrogen in the side chain must specifically interact
      with aspartate 351 makes this the key to the antiestrogenic activity of
      raloxifene.

PMID- 9581829
TI  - Human DNA topoisomerase IIalpha-dependent DNA cleavage and yeast cell killing by
      anthracycline analogues.
AB  - Anthracyclines are among the most clinically useful topoisomerase II poisons. A
      complete understanding of their molecular mechanism is thus fundamental for a
      rational design of novel agents. We evaluated four anthracycline analogues with
      respect to human topoisomerase IIalpha-dependent DNA cleaving activity,
      efficiency in killing yeast cells, and uptake and retention in yeast and compared
      the yeast system to tumor cell line models. The yeast JN394top2-4 strain was used
      because it has a topoisomerase II ts gene mutation: enzyme activity is much less
      at 30 degrees C than at 25 degrees C and is completely lost at 35 degrees C.
      Untransformed JN394top2-4 cells were 33-fold more sensitive to idarubicin at 25
      degrees C than at 30 degrees C, showing that topoisomerase II is the primary drug
      target. Overexpression of human topoisomerase IIalpha was toxic to yeast cells
      when the yeast enzyme was inactivated. Drug-dependent killing of yeast cells
      expressing low levels of the human alpha isoenzyme at 35 degrees C showed that
      the analogues spanned a 3-log range of cytotoxic potency in yeast, as they did in
      tumor cells. However, the compounds were much less active against the yeast
      strain than mammalian tumor cell lines. Drug uptake was determined and found to
      be altered in yeast with respect to tumor cells. Although DNA cleavage stimulated
      by anthracyclines roughly correlated with cytotoxicity, the cleavage
      level:cytotoxicity ratios were different for the studied drugs. Thus, the results
      suggest that other drug-dependent molecular factors contribute to drug activity
      in addition to the cellular content of topoisomerase IIalpha and drug uptake.

PMID- 9581828
TI  - Induction of apoptosis in MCF-7:WS8 breast cancer cells by beta-lapachone.
AB  - Beta-lapachone (beta-lap) affects a number of enzymes in vitro, including type I
      topoisomerase (Topo I); however, its exact intracellular target(s) and mechanism
      of cell killing remain unknown. We compared the cytotoxic responses of MCF-7:WS8
      (MCF-7) human breast cancer cells after 4-h pulses of beta-lap or camptothecin
      (CPT), a known Topo I poison. A direct correlation between loss of survival and
      apoptosis was seen after beta-lap treatment (LD50 = 2.5 microM). A concentration
      dependent, transient sub-2 N preapoptotic cell population was observed at 4-8 h.
      Estrogen deprivation-induced synchronization and bromodeoxyuridine-labeling
      studies revealed an apoptotic exit point near the G1-S border. Apoptosis
      activated by beta-lap was closely correlated with cleavage of lamin B but not
      with increases in p53/p21 or decreases in bcl-2. Loss of hyperphosphorylated
      forms of the retinoblastoma protein was observed within 5 h, but cyclins A, B1,
      and E levels were unaltered for up to 72 h after 5 microM beta-lap. Topo I and
      Topo IIalpha levels decreased at > 24 h. Logarithmic-phase MCF-7 cells were not
      affected by < or = 1 microM beta-lap. In contrast, dramatic and irreversible G2-M
      arrest with no apoptosis was observed in MCF-7 cells treated with 1 microM CPT,
      monitored for 6-10 days posttreatment. MCF-7 cells treated with supralethal doses
      of CPT (5 microM) resulted in only approximately 20% apoptosis. No correlation
      between apoptosis and loss of survival was observed. MCF-7 cells exposed to > 5
      microM CPT arrested at key cell cycle checkpoints (i.e., G1, S, and G2-M), with
      little or no movement for 6 days. Ten-fold increases in p53/p21 and 2-5-fold
      decreases in bcl-2, Topo I, Topo IIalpha, and cyclins A and B1, with no change in
      cyclin E, were observed. Temporal decreases in bcl-2 and cleavage of lamin B
      corresponded to the minimal apoptotic response observed. Beta-lap activated
      apoptosis without inducing p53/p21 or cell cycle arrest responses and killed MCF
      7 cells solely by apoptosis. In contrast, concentration-dependent increases in
      nuclear p53/p21 and various cell cycle checkpoint arrests were seen in MCF-7
      cells after CPT. Despite dramatic p53/p21 protein induction responses, CPT
      treated MCF-7 cells showed low levels of apoptosis, possibly due to protective
      cell cycle checkpoints or the lack of specific CPT-activated apoptotic pathways
      in MCF-7 cells.

PMID- 9581830
TI  - Intracellular expression of a single-chain antibody directed against human
      papillomavirus type 16 E7 oncoprotein achieves targeted antineoplastic effects.
AB  - Human papillomavirus type 16 (HPV16) E7 is a viral oncoprotein that is believed
      to play a major role in cervical neoplasia. Anti-HPV16 E7 intracellular single
      chain antibodies (scFvs) were constructed to down-regulate HPV16 E7 oncoprotein
      in HPV DNA-containing cell lines. In these studies, we transfected anti-E7 scFvs
      into the HPV16-positive human cervical carcinoma cell lines CaSki and SiHa and
      tested them for their ability to inhibit cell proliferation and alter the level
      of HPV16 E7 oncoprotein. Our results showed that anti-HPV16 E7 scFvs inhibited
      cell proliferation by >85% in CaSki cells and by 95% in SiHa cells. E7
      oncoprotein was down-regulated by anti-HPV16 E7 scFv, and its expression was
      inversely related to the amount of scFv transfected. However, there were no
      effects of transfecting scFvs alone in HPV-negative cell lines. These results
      imply that anti-HPV16 E7 scFvs only have specific anti-HPV16 E7 effects on cell
      proliferation and on the synthesis of virally encoded proteins in HPV-positive
      cell lines. Thus, transfection of HPV16 E7-positive tumors with antigen-specific
      scFvs may be a viable strategy for cervical cancer gene therapy.

PMID- 9581831
TI  - Heterogeneity of intracellular pH and of mechanisms that regulate intracellular
      pH in populations of cultured cells.
AB  - Cells within solid tumors are known to exist in a microenvironment that may be
      acidic and depend on membrane-based mechanisms (Na+/H+ antiport and Na+-dependent
      Cl-/HCO3- exchanger) that regulate intracellular pH (pHi). We have used the
      fluorescent pH indicator 2',7'-bis-(2-carboxyethyl) 5 (and 6)-carboxyfluorescein
      and flow cytometry to study the distribution of pHi and the activity of these pHi
      regulating mechanisms among populations of murine mammary sarcoma (EMT6), human
      breast cancer (MCF-7), and Chinese hamster ovary cells exposed to different
      levels of extracellular pH (pHe). Cells were exposed to Na+ buffer in the
      presence or absence of HCO3- and of 5-(N-ethyl-N-isopropyl)-amiloride (a potent
      inhibitor of the Na+/H+ antiport) to determine the relative importance of each
      exchanger in the regulation of pHi. Our results indicate that: (a) the
      distribution of pHi at any value of pHe is broader than can be accounted for by
      machine noise; (b) cells maintain levels of pHi that are higher than pHe under
      acidic conditions; (c) the distribution of pHi is narrower when the Na+-dependent
      Cl-/HCO3- exchanger is active; and (d) populations that are derived from selected
      cells with values of pHi at lower and higher ends of the pHi distribution
      generate pHi distributions that are similar to those of controls, suggesting a
      stochastic variation in the activity of membrane-based mechanisms that regulate
      pHi. Our data suggest that the Na+-dependent Cl-/HCO3- exchanger is the dominant
      mechanism for regulation of pHi under moderately acidic conditions such as may
      occur in the microenvironment of solid tumors.

PMID- 9581832
TI  - Telomerase from human leukemia cells: properties and its interaction with
      deoxynucleoside analogues.
AB  - Telomerase is a unique reverse transcriptase involved in the maintenance of
      genomic integrity. In an attempt to understand the properties of this enzyme and
      to study the effect of deoxynucleoside analogues, we have isolated and partially
      purified telomerase from the blast cells of a patient with acute myelogenous
      leukemia. During the course of purification of telomerase, three characteristic
      forms of this enzyme activity were separated. Two processive forms and one less
      processive form were noted. All forms of the enzyme activities could be abolished
      by RNase A and proteinase K treatments, implying that they are
      ribonucleoproteins. The major form of telomerase was characterized with respect
      to divalent ion requirements, effect of salt and nonionic detergents. The Km of
      deoxynucleoside triphosphates was determined with a modified telomerase repeat
      array protocol assay. Studies with deoxynucleoside analogues indicated that 3'
      azido-3'deoxythymidine triphosphate is much more inhibitory than 2',3'-dideoxy
      2',3'didehydrothymidine triphosphate, and the cytidine analogue ddCTP was not
      inhibitory. ddGTP was the most potent inhibitor among all dideoxynucleosides
      studied.

PMID- 9581833
TI  - Prolactin activates Stat1 but does not antagonize Stat1 activation and growth
      inhibition by type I interferons in human breast cancer cells.
AB  - Type I interferons (IFN alpha and IFN beta) are presently used in the adjuvant
      treatment of several human cancers. However, these cytokines have demonstrated
      only modest success in breast cancer therapy, and research efforts have focused
      on improving their efficacy. Recent progress in understanding the molecular
      mechanisms underlying the antiproliferative effects of IFNs has identified the
      cytoplasmic transcription factor Stat1 as a critical mediator. It is, therefore,
      possible that IFN-induced growth inhibition of mammary epithelial cells is
      counteracted by other cytokines that also use Stat1. One such candidate IFN
      antagonist with particular relevance to breast cancer is the mammotropic hormone
      prolactin (PRL). The main goal of this study was to examine whether PRL would
      interfere with type I IFN (IFN alpha/beta) signal transduction by competing for
      limited cytoplasmic Stat factors. A second aim was to test whether pretreatment
      of mammary tumor cell lines with IFN gamma could enhance the effect of IFN
      alpha/beta. By analyzing the effect of PRL on IFN alpha/beta-induced tyrosine
      phosphorylation of Stat proteins and their binding to IFN-regulated genes, we now
      report that costimulation of PRL receptors did not interfere with IFN alpha/beta
      signals in several human breast cancer cell lines, including T47D, MCF-7, and BT
      20. Specifically, PRL did not affect IFN alpha/beta-induced tyrosine
      phosphorylation or heterodimerization of Stat1 and Stat2 in any cell line.
      Instead, IFN alpha/beta- and PRL-induced tyrosine phosphorylation of Stat1 was
      additive and occurred without evidence of competition for limited concentrations
      of cytoplasmic Stat1. A similar additive relationship was observed on IFN
      alpha/beta- and PRL-induced Stat3 tyrosine phosphorylation. Furthermore,
      electrophoretic mobility shift assays showed that type I IFNs induced
      predominantly Stat1-Stat2 or Stat1-Stat3 heteromeric complexes with various IFN
      response elements of IFN-stimulated genes, whereas PRL induced Stat1 homodimers.
      Despite significant mutual use of Stats by IFNs and PRL, these results indicated
      a high degree of signaling specificity in the two receptor systems, and that
      cytoplasmic levels of Stat proteins were not limiting. Similarly, PRL did not
      interfere with the growth-inhibitory effect of IFN beta. On the other hand, the
      study indicated that pretreatment of human breast cancer cell lines with IFN
      gamma enhanced the growth-inhibitory action of type I IFNs, suggesting a possible
      avenue for improving the effect of type I IFNs in the treatment of breast cancer
      patients.

PMID- 9581834
TI  - A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and
      induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic
      effects in human prostate carcinoma DU145 cells.
AB  - Prostate cancer (PCA) is the most common nonskin malignancy and the second
      leading cause of cancer deaths in United States males. One practical and
      translational approach to control PCA is to define a mechanism-based
      anticarcinogenic agent(s). Recently, we showed that silymarin, a flavonoid
      antioxidant isolated from milk thistle, possesses exceptionally high to complete
      protective effects against experimentally induced tumorigenesis. Because the
      epidermal growth factor receptor (erbB1) and other members of the erbB family
      have been shown to play important roles in human PCA, efforts should be directed
      to identify inhibitors of this pathway for PCA intervention. In this study, we
      assessed whether silymarin inhibits erbB1 activation and associated downstream
      events and modulates cell cycle regulatory proteins and progression, leading to
      growth inhibition of human prostate carcinoma DU145 cells. Treatment of serum
      starved cells with silymarin resulted in a significant inhibition of transforming
      growth factor alpha-mediated activation of erbB1 but no change in its protein
      levels. Silymarin treatment of cells also resulted in a significant decrease in
      tyrosine phosphorylation of an immediate downstream target of erbB1, the adapter
      protein SHC, together with a decrease in its binding to erbB1. In the studies
      analyzing cell cycle regulatory molecules, silymarin treatment of cells also
      resulted in a significant induction of cyclin-dependent kinase inhibitors (CDKIs)
      Cip1/p21 and Kip1/p27, concomitant with a significant decrease in CDK4
      expression, but no change in the levels of CDK2 and CDK6 and their associated
      cyclins E and D1, respectively. Cells treated with silymarin also showed an
      increased binding of CDKIs with CDKs, together with a marked decrease in the
      kinase activity of CDKs and associated cyclins. In additional studies, treatment
      of cells grown in 10% serum with anti-epidermal growth factor receptor monoclonal
      antibody clone 225 or different doses of silymarin also resulted in significant
      inhibition of constitutive tyrosine phosphorylation of both erbB1 and SHC but no
      change in their protein levels. Furthermore, whereas silymarin treatment resulted
      in a significant increase in the protein levels of both Cip1/p21 and Kip1/p27,
      monoclonal antibody 225 showed an increase only in Kip1/p27. These findings
      suggest that silymarin also inhibits constitutive activation of erbB1 and that
      the observed effect of silymarin on an increase in CDKI protein levels is
      mediated via inhibition of erbB1 activation only in the case of Kip1/p27;
      however, additional pathways independent of inhibition of erbB1 activation are
      possibly responsible for the silymarin-caused increase in Cip1/p21 in DU145
      cells. In other studies, silymarin treatment also induced a G1 arrest in the cell
      cycle progression of DU145 cells and resulted in a highly significant to complete
      inhibition of both anchorage-dependent and anchorage-independent growth of DU145
      cells in a dose- and time-dependent manner. Taken together, these results suggest
      that silymarin may exert a strong anticarcinogenic effect against PCA and that
      this effect is likely to involve impairment of erbB1-SHC-mediated signaling
      pathway, induction of CDKIs, and a resultant G1 arrest.

PMID- 9581835
TI  - A peptidomimetic antagonist of the integrin alpha(v)beta3 inhibits Leydig cell
      tumor growth and the development of hypercalcemia of malignancy.
AB  - The integrin alpha(v)beta3 interacts with the arginine-glycine-aspartic acid
      (RGD) tripeptide recognition sequence of a variety of extracellular matrix
      proteins. Recent studies show that alpha(v)beta3 plays an important role in tumor
      induced angiogenesis and tumor growth and that antagonists of alpha(v)beta3
      inhibit angiogenic processes that include endothelial cell adhesion and
      migration. Consequently, we reasoned that an RGD-based peptidomimetic antagonist
      of alpha(v)beta3 might inhibit tumor angiogenesis and tumor growth in vivo. An
      RGD-peptidomimetic library was screened to identify antagonists of vitronectin
      binding to alpha(v)beta3, and the compounds chosen were modified to produce
      selective and potent inhibitors of alpha(v)beta3. One of these compounds, beta
      [[2-2-[[[3-[(aminoiminomethyl)amino]-phenyl]carbonyl]amino]ac etyl]amino]-3,5
      dichlorobenzenepropanoic acid (SC-68448), inhibited vitronectin binding to both
      alpha(v)beta3 and the closely related platelet receptor, alpha(IIb)beta3, in a
      dose-responsive manner. SC-68448 inhibited vitronectin binding to alpha(v)beta3
      (IC50, 1 nM) and fibrinogen binding to the platelet receptor alpha(IIb)beta3
      (IC50, >100 nM), demonstrating that SC-68448 was 100-fold more potent as an
      inhibitor of alpha(v)beta3 versus alpha(IIb)beta3. In cell-based studies, SC
      68448 inhibited alpha(v)beta3-mediated endothelial cell proliferation in a dose
      dependent manner but did not inhibit tumor cell proliferation, suggesting that
      effects on endothelial cell proliferation were not due to SC-68448-induced
      cytotoxicity. In accord with these results, SC-68448 inhibited angiogenesis in
      vivo in a basic fibroblast growth factor-induced rat corneal neovascularization
      model. A xenogeneic severe combined immune deficiency mouse/rat Leydig cell tumor
      model was developed for testing SC-68448 as an inhibitor of tumor growth in vivo.
      Rat Leydig cell tumors grew rapidly in severe combined immune deficiency mice and
      produced humoral hypercalcemia of malignancy. SC-68448 inhibited the growth of
      the tumors in mice by up to 80% and completely blocked the development of
      hypercalcemia. Together, these results demonstrate the feasibility of antitumor
      therapies based upon the development of nontoxic small molecule pharmacological
      antagonists of integrin alpha(v)beta3.

PMID- 9581836
TI  - Isolation of human O6-alkylguanine-DNA alkyltransferase mutants highly resistant
      to inactivation by O6-benzylguanine.
AB  - The activity of O6-alkylguanine-DNA alkyltransferase (AGT) protects cells from
      killing by methylating or chloroethylating agents. AGT is strongly inhibited by
      O6-benzylguanine (ED50, 0.2 microM), and this drug is presently undergoing
      clinical trials to enhance chemotherapy by alkylating agents. Point mutations
      such as P140A (ED50, 5 microM) render AGT resistant to O6-benzylguanine (BG).
      Selection for such mutants may prove to be a problem in the use of BG, and a
      better knowledge of the factors underlying resistance to BG will enable the
      rational design of improved inhibitors able to inactivate these mutants. BG
      resistant AGT mutants may also be valuable for expression in bone marrow stem
      cells to reduce myelosuppression brought about by alkylating agents, to increase
      the therapeutic index of therapies including BG, and for use as a selectable
      marker to allow other genes to be expressed in such stem cells. We have therefore
      set up a general screen to obtain such mutants by using the ability of AGT to
      protect Escherichia coli GWR109 lacking endogenous AGT from killing by N-methyl
      N'-nitro-N-nitrosoguanidine. When the cells were rendered permeable to BG by
      mutating the lipopolysaccharide membrane component forming strain TRG8, the
      protection by AGT expression was abolished by treating the cells with BG. The
      known P140A mutant was used to test the system and was highly selected for by
      treatment with 50 microM BG and 40 microg/ml N-methyl-N'-nitro-N
      nitrosoguanidine. The sequence coding for PVP at positions 138-140 in AGT was
      replaced with a random nucleotide sequence, and this library was used to
      transform TRG8. All of the 59 colonies analyzed having AGT activity that survived
      the selection from the pool of 36,000 transformants were resistant to BG. Many
      (69%) of these mutants contained lysine at position 140, and all of these showed
      the highest level of resistance with <10% loss of activity when crude cell
      extracts were incubated with 1.2 mM BG. This result was confirmed with three
      mutants (P138K/V139L/P140K, P138M/V139L/P140K, and P140K), which were purified to
      homogeneity. The next most common residues found at position 140 were arginine
      (7%) and asparagine (7%). Studies carried out with purified preparations of
      mutants P140R and P140N revealed that these mutations also provided resistance to
      BG but to a lesser extent than P140K (ED50s of 190 and 7 microM, respectively).
      These results indicate that: (a) this screening method can be used to evaluate BG
      resistance of single or multiple changes throughout the AGT sequence; and (b)
      replacement of proline-140 with lysine is the most effective point mutation at
      this site causing BG resistance and is more than 200 times more effective than
      replacement with alanine.

PMID- 9581837
TI  - Adenovirus-mediated transduction of Escherichia coli uracil
      phosphoribosyltransferase gene sensitizes cancer cells to low concentrations of 5
      fluorouracil.
AB  - 5-fluorouracil (5-FU), although a widely used chemotherapeutic agent, has a
      limited effect in the treatment of human solid tumors due to their resistance to
      the cytotoxic effects of 5-FU. Escherichia coli uracil phosphoribosyltransferase
      (UPRT) is a pyrimidine salvage enzyme that catalyzes the synthesis of UMP from
      uracil and 5-phosphoribosyl-alpha-1-diphosphate. The present study demonstrates
      that adenovirus-mediated transduction of E. coli UPRT gene results in marked
      sensitization of colon, gastric, liver, and pancreas cancer cell lines to low
      concentration of 5-FU in vitro. The in vitro bystander effect was observed when
      only 10% of the hepatoma Hep3B cells were infected with UPRT-expressing
      adenovirus. In addition, 5-FU treatment of human hepatoma or gastric cancer
      xenografts in nude mice transduced with UPRT was demonstrated to result in
      significant in vivo antitumor effects. The adenovirus vector transduction of the
      UPRT gene followed by 5-FU administration is representative of a new
      chemosensitization strategy for cancer gene therapy.

PMID- 9581838
TI  - Vascular endothelial growth factor as a marker of tumor endothelium.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that is
      a primary stimulant of the vascularization of solid tumors. VEGF production is
      induced by oncogenic gene mutations in the tumor cells and by hypoxic conditions
      inside the tumor mass. Hypoxia and the locally increased concentration of VEGF
      lead to an up-regulation of VEGF receptor expression on tumor endothelial cells.
      Therefore, in the tumor microenvironment, there is an up-regulation of both VEGF
      and its receptor, leading to a high concentration of occupied receptor on tumor
      vascular endothelium. The VEGF:receptor complex presents an attractive target for
      the specific delivery of drugs or other effectors to tumor endothelium. In the
      present study, several hybridomas that secrete monoclonal antibodies against the
      VEGF:receptor (Flk-1) complex or against VEGF itself have been raised. Three of
      the antibodies (3E7, GV39M, and 11B5) bind with high affinity to the VEGF:Flk-1
      complex in ELISA and to tumor endothelium in frozen sections of human tumors,
      rodent tumors, and human tumor xenografts. 3E7 and GV39M localize selectively to
      tumor endothelium after i.v. injection into mice bearing human tumor xenografts.
      Additionally, one antibody (2C3) was raised that blocks the interaction between
      VEGF and KDR/Flk-1. 2C3 inhibits VEGF-mediated growth of endothelial cells in
      vitro and localizes strongly to connective tissue in tumors after injection into
      mice bearing human tumor xenografts. These findings suggest that 3E7, GV39M, and
      2C3 are candidates for targeting and imaging the vasculature or connective tissue
      of tumors.

PMID- 9581839
TI  - Vaccination with multiple antigen peptide as rejection antigen peptide in murine
      leukemia.
AB  - pRL1a (IPGLPLSL) is the Ld-binding tumor rejection antigen peptide recognized by
      CTLs on BALB/c radiation leukemia RL(male)1. We demonstrated that in vivo and in
      vitro sensitization with pRL1a multiple antigen peptide (MAP), but not with the
      pRL1a peptide itself, generated pRL1a-specific CTLs in the spleen cells of BALB/c
      mice. No enhancement of cytotoxicity was observed by emulsifying pRLla MAP in
      incomplete Freund's adjuvant or in complete Freund's adjuvant for in vivo
      sensitization. Selective depletion of CD4+ T cells in mice by treatment with anti
      L3T4 (CD4) monoclonal antibody and that of macrophages by treatment with
      carrageenan on in vivo sensitization with pRL1a MAP abrogated CTL generation. The
      findings suggest that CD4+ T cells and antigen-presenting cells were necessary
      for the in vivo priming of CD8+ T cells with pRL1a MAP. Furthermore, we
      demonstrated that in vivo sensitization of BALB/c mice with pRL1a MAP, but not
      with pRL1a peptide, showed an inhibitory effect on RL(male)1 tumor growth. No
      growth-inhibitory effect was observed on control RVA, RVD, or Meth A tumors.

PMID- 9581840
TI  - DNA vaccines encoding full-length or truncated Neu induce protective immunity
      against Neu-expressing mammary tumors.
AB  - We generated DNA expression vectors encoding the full-length neu cDNA (designated
      pNeuN), the neu extracellular domain (pNeuE), or the neu extracellular and
      transmembrane domains (pNeuTM). The 293 cells transfected with pNeuN or pNeuTM
      expressed the neu extracellular domain on the surface membrane, whereas 293 cells
      transfected with pNeuE secreted the extracellular domain of neu into the culture
      supernatant. We examined whether i.m. injection of either of these plasmids could
      induce protective immunity in FVB/N mice against the adoptive transfer of Tgl-1
      cells, a neu-expressing tumor cell line generated from a mouse mammary tumor that
      spontaneously arose in a FVB/N neu-transgenic mouse. The i.m. injection of pNeuTM
      or pNeuE, and to a lesser extent pNeuN, induced protective immunity against a
      subsequent challenge with Tgl-1 cells in FVB/N mice. In addition, the coinjection
      of a plasmid encoding interleukin-2 (designated pIL-2) augmented the efficacy of
      each of the pNeu plasmids for inducing protective immunity. The plasmid pNeuTM
      seemed to be the most effective for inducing anti-neu antibodies. However, the
      generation of detectable anti-neu antibodies in response to any one of these pNeu
      plasmids was not enhanced by coinjection of pIL-2 and was not required for
      protective immunity against Tgl-1 cells. These studies demonstrate that DNA
      expression vectors encoding soluble or membrane-bound forms of neu lacking the
      cytoplasmic kinase domain can be effective in inducing protective antitumor
      immunity.

PMID- 9581841
TI  - Mechanisms of inactivation of E-cadherin in breast cancer cell lines.
AB  - Loss of E-cadherin (CDH1) function is thought to contribute to progression in
      breast cancer and other solid tumors by increasing proliferation, invasion,
      and/or metastasis. In some cases, the restoration of CDH1 function may be an
      important therapeutic option. This possibility will depend on the mechanism by
      which CDH1 is inactivated. Here we present analyses of CDH1 expression, genetic
      mutation, and promoter methylation in CDH1 in 10 commonly used breast cancer cell
      lines. Five cell lines (BT-474, MCF-7, MDA-MB-361, MDA-MB-468, and T-47D)
      expressed CDH1 and were genetically normal. Five others (SK-BR-3, 600 MPE, MDA-MB
      134 IV, CAMA1, and MDA-MB-435) did not express CDH1. Fluorescence in situ
      hybridization analyses of each of these cell lines showed evidence for the
      physical deletion of one allele of CDH1, and three cell lines were found to carry
      homozygous deletions. SK-BR-3 was deleted from exon 12 through the promoter; exon
      6 was deleted in MDA-MB-134 IV cells, and 600 MPE cells carried a 21-bp deletion
      in the splicing acceptor site for exon 9. CAMA1 seemed to have been inactivated
      through promoter methylation. No explanation was found for the inactivation of
      CDH1 in MDA-MB-435.

PMID- 9581842
TI  - Impairment of nucleotide excision repair by apoptosis in UV-irradiated mouse
      cells.
AB  - We investigated the relationship between nucleotide excision repair (NER)
      activity and apoptosis in UV-irradiated cells. Mouse erythroleukemia (MEL) and
      lymphoma (GRSL) cells exhibited enhanced sensitivity to the cytotoxic effects of
      UV radiation compared to hamster cell lines, although normal UV-induced hprt
      mutation frequencies were found. Determination of UV-induced repair replication
      revealed a limited capacity of MEL and GRSL cells to perform NER consistent with
      poor removal of cyclobutane pyrimidine dimers and pyrimidine 6-4 pyrimidone
      photoproducts from transcriptionally active genes during the first 8 h after UV
      exposure. However, both cyclobutane pyrimidine dimers and pyrimidine 6-4
      pyrimidone photoproducts appeared to be processed to almost normal level 24 h
      after UV treatment. In parallel, we observed that the UV-irradiated MEL and GRSL
      cells suffered from severe DNA fragmentation particularly 24 h after UV exposure.
      Taken together, these data indicate a reduced repair of UV-induced photolesions
      in apoptotic cells, already established at the early onset of apoptosis. To test
      whether inhibition of repair in cells was due to inactivation of NER or to
      apoptosis-induced chromatin degradation, we performed in vitro excision assays
      using extracts from UV-irradiated MEL cells. These experiments showed that the
      NER capacity during early apoptosis was intact, indicating that slow removal of
      UV-induced photolesions in apoptotic cells is due to substrate modification
      (presumably degradation of chromatin) rather than direct inhibition of factors
      involved in NER.

PMID- 9581843
TI  - Functional characterization of transforming growth factor beta type II receptor
      mutants in human cancer.
AB  - We recently identified missense mutations at amino acid residues 526 and 537
      located within the highly conserved subdomain XI of the transforming growth
      factor beta type II receptor (TbetaR-II) serine-threonine kinase in two human
      squamous carcinoma cell lines. These cell lines are resistant to transforming
      growth factor beta-mediated inhibition of growth. Moreover, treatment with
      transforming growth factor beta fails to increase the levels of type 1
      plasminogen activator inhibitor and fibronectin synthesis. To test the effects of
      the mutations on receptor function, mutant TbetaR-II cDNAs were expressed in
      TbetaR-II-deficient T47D cells. Cyclin A promoter activity was reduced by 50% in
      cells expressing wild-type TbetaR-II but increased 2-fold in cells transfected
      with either of the two mutant receptors. Conversely, plasminogen activator
      inhibitor type 1 promoter activity was increased 6-fold in cells transfected with
      wild-type receptor but not with either of the two mutant receptors. Moreover, the
      activity of both mutant serine-threonine kinases was strongly reduced compared to
      that of the wild-type receptor. Thus, the amino acid residues at positions 526
      and 537 seem to be essential for kinase function and signaling activity of the
      TbetaR-II.

PMID- 9581844
TI  - p53-dependent signaling sustains DNA replication and enhances clonogenic survival
      in 254 nm ultraviolet-irradiated human fibroblasts.
AB  - The cyclin-dependent kinase inhibitor p21(WAF1/CIP1/SDI1/CAP20) exists in normal
      human fibroblasts in a quaternary complex with a cyclin, a cyclin-dependent
      kinase, and proliferating cell nuclear antigen. A model was proposed in which,
      during p53-mediated suppression of cell proliferation following treatment with
      254 nm UV radiation (UVC), the enhanced expression of p21 might inhibit DNA
      replication by virtue of its interactions with proliferating cell nuclear
      antigen. To test this model, we examined the mechanisms of inhibition of DNA
      replication in diploid human fibroblasts that express human papillomavirus type
      16 E6, which inactivates p53. E6-expressing cells were defective in G1 checkpoint
      responses of induction of p21 and G1 arrest after ionizing radiation-induced
      damage to DNA. Accordingly, E6-expressing cells were resistant to inactivation of
      single-cell colony formation by ionizing radiation. E6 cells also displayed
      normal S-phase checkpoint responses of inhibition and recovery of replicon
      initiation following exposure to ionizing radiation and normal ability to bypass
      pyrimidine dimers during DNA replication soon after UVC irradiation (i.e.,
      postreplication repair). However, DNA replication 6 h after UVC exposure was
      significantly inhibited in E6 cells in comparison to isogenic controls. This
      failure to maintain DNA replication in S-phase cells was associated with enhanced
      sensitivity to inactivation of single-cell colony formation by UVC. These results
      indicate that the p53-induced p21 pathway is not involved in the immediate S
      phase responses to radiation-induced DNA damage of inhibition of replicon
      initiation and translesion bypass. However, our results demonstrate that p53 and,
      conceivably, p21 contribute to the ability of normal human fibroblasts to sustain
      DNA replication activity and form colonies following UVC irradiation.

PMID- 9581845
TI  - Synchronous oral carcinomas: independent or common clonal origin?
AB  - Second primary tumors in patients with head and neck cancer have a detrimental
      impact on long-term survival; at least 15% of patients develop additional tumors.
      Originally, it was hypothesized that multiple tumors developed independently
      after widespread epithelial exposure to carcinogens (the field cancerization
      theory), but recent molecular studies now support the alternative theory of a
      common clonal origin. If multiple tumors originate from the same clone, early
      genetic alterations in these cells should be common to all of the tumors. We have
      compared the pattern of allelic imbalance in paired tumors from five male
      patients with two synchronous oral squamous cell carcinomas and in peripheral
      dysplasia using microsatellite markers on chromosomes 3p, 9p, and 17p.
      Discordance, usually through loss of alternate alleles at the same microsatellite
      loci, was detected in two patients. The remaining three patients had identical
      alterations in their tumors. The changes identified occurred early in
      tumorigenesis, because, with only one exception, these were also present in the
      associated dysplasia. Thus, we provide evidence that synchronous oral squamous
      cell carcinomas are of independent origin in some patients but may be of common
      clonal origin in others.

PMID- 9581846
TI  - 4-Oxoretinol, a metabolite of retinol in the human promyelocytic leukemia cell
      line NB4, induces cell growth arrest and granulocytic differentiation.
AB  - All-trans-retinoic acid (RA) is used as a differentiation therapy for acute
      promyelocytic leukemia. Patients can become resistant to RA, and this resistance
      is thought to be mediated in part by an increase in the rate of RA metabolism. We
      have characterized the metabolism of all-trans-retinol (ROL; vitamin A) in NB4
      cells, which are human promyelocytic leukemia cells. NB4 cells metabolize ROL
      into a variety of compounds, including all-trans-4-hydroxyretinol, all-trans-4
      oxoretinol (4-oxoROL), 14-hydroxy-4,14-retro-retinol, anhydroretinol, and several
      ROL esters. No metabolism of ROL to RA or to RA derivatives in NB4 cells was
      detected. The rate of ROL metabolism increased after cell differentiation; in a
      24-h period, differentiated cells metabolized 2-fold more ROL than did
      undifferentiated cells. The major difference in the ROL metabolism pattern
      between undifferentiated and differentiated cells was an approximately 10-fold
      increase in the production of all-trans-4-hydroxyretinol and 4-oxoROL in
      differentiated cells. Furthermore, exogenously added 4-oxoROL was capable of
      eliciting NB4 cell differentiation, as measured by growth inhibition, nitroblue
      tetrazolium reduction, nuclear body relocalization of PML, and surface expression
      of CD11b. In addition, 4-oxoROL synergized with IFN-gamma in the promotion of NB4
      cell growth arrest. Following treatment of NB4 cells with 4-oxoROL to induce
      differentiation, the production of 4-oxoROL from ROL was observed; this indicated
      that 4-oxoROL induces its own synthesis in NB4 cells. In addition, 48 h after the
      administration of 1 microM 4-oxoROL, NB4 cells maintained a high intracellular
      concentration (17 microM) of 4-oxoROL. These unique properties of 4-oxoROL may
      provide advantages over RA in the treatment of promyelocytic leukemia cells
      because it may be possible to maintain cytodifferentiating concentrations of 4
      oxoROL in the cells for extended periods of time.

PMID- 9581847
TI  - Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast
      cancer cell lines.
AB  - Two breast cancer cell lines, YMB-S and ZR-75-1S, were established in our
      laboratory. They proliferated in suspension culture without aggregation in a
      complete liquid medium. We found that sodium butyrate (NaB) arrested the cells in
      the G0-G1 phase of the cell cycle, inhibited their proliferation, and induced
      cell-cell and cell-surface adhesion. In this study, we explored the mechanism of
      this adhesion. Adhesion was inhibited by an anti-E-cadherin antibody, suggesting
      a role for E-cadherin. However, there were no changes in the expression of E
      cadherin, alpha-catenin, and beta-catenin. Northern blot analysis and
      cytofluorometry revealed that NaB-treated cells showed a lower expression of MUC1
      than did untreated cells. To examine the possibility that the adhesion of these
      cells might be induced by decreased MUC1 expression, the level of MUCI expression
      was directly reduced using an antisense oligonucleotide. The MUC1 antisense
      oligonucleotide induced cell-cell and cell-surface adhesion of these breast
      cancer cells, just as NaB did. Our observations indicate that E-cadherin can be
      functionally suppressed by overexpression of MUC1 but resumes its activity after
      suppression of MUC1 expression. Thus, regulation of MUC1 might be a new strategy
      for cancer therapy.

PMID- 9581848
TI  - Overexpression of a transmembrane isoform of neural cell adhesion molecule alters
      the invasiveness of rat CNS-1 glioma.
AB  - CNS-1 is a highly invasive neural cell adhesion molecule (NCAM)-positive rat
      glioma that exhibits similarities in its pattern of infiltration to human
      gliomas. To investigate whether increasing NCAM expression alters invasive
      behavior, retroviruses encoding human NCAM 140 and a cytoplasmic truncation of
      NCAM 140 were used to transduce a population of CNS-1 glioma cells that had a
      relatively low endogenous level of NCAM. Compared to cells transduced with a
      control virus, cells overexpressing either intact or truncated human NCAM 140
      showed decreased invasion of a reconstituted basal lamina. Changes in growth rate
      or in key matrix metalloproteinase activities could not account for this result.
      In a migration assay on type IV collagen, cells exhibited a substrate
      concentration-dependent increase in the rate of migration; however,
      overexpression of NCAM 140 or truncated NCAM 140 inhibited motility at higher
      substrate concentrations. Consistent with these findings was the decreased spread
      of NCAM 140 overexpressers in vivo following instillation of cells into the right
      frontal cortex of rat brain. NCAM 140 overexpressers showed considerably more
      restricted perivascular and periventricular spread than cells transduced with a
      control virus. However, NCAM-140-overexpressing tumor exhibited a less cohesive
      pattern of growth near the site of tumor instillation and more individual cell
      infiltration of brain parenchyma with more pronounced perineuronal satellitosis.
      The stability of recombinant NCAM expression was confirmed by recovering tumor
      cells from tumor-bearing animals and measuring NCAM levels by flow cytometry.
      These observations show that overexpression of NCAM 140 decreases the long-range
      spread of CNS-1 glioma along basal lamina pathways but enhances local
      infiltration of neuropil.

PMID- 9581849
TI  - Mutant RAS selectively promotes sensitivity of myeloid leukemia cells to
      apoptosis by a protein kinase C-dependent process.
AB  - RAS mutations arise at high frequency in human malignancy and have been shown to
      play a role in the disruption of both normal differentiation and proliferation.
      In addition, RAS influences a number of intracellular signaling pathways, which
      impinge on proteins that regulate programmed cell death. In this study, we have
      examined whether this oncogene can influence the activation of the apoptotic
      process induced by a range of therapeutic agents used to treat leukemia, and we
      have identified the downstream targets of RAS mediating the observed changes in
      sensitivity. Using myeloid leukemia cells (P39) retrovirally transduced with
      mutant H-RAS, we found that the influence of this oncogene was highly dependent
      on the inducer used: whereas RAS had no significant effect on spontaneous
      apoptosis or on the response to the cytotoxic drugs (doxorubicin or 1-beta
      arabinofuranosylcytosine), P39-RAS cells showed a strongly augmented response to
      all-trans-retinoic acid (ATRA) in both the induction of apoptosis and
      differentiation. Because, under some circumstances, RAF has been associated with
      promoting apoptosis, we examined whether the activation of this kinase by mutant
      RAS could be responsible for the augmented response to ATRA. However,
      constitutive activation of RAF did not alter the apoptotic sensitivity of these
      cells, making it unlikely that RAS promotes apoptosis by stimulating this kinase.
      Nor did we find that BCL-2 was differentially down-regulated in P39-RAS cells.
      Rather, we found that the activation of protein kinase C (PKC) by low-dose
      phorbol ester could almost entirely recapitulate transformation by RAS, in terms
      of promoting both apoptosis and differentiation after treatment with ATRA.
      Moreover, the RAS-induced phenotype could be completely abolished by a specific
      inhibition of PKC under conditions that had no effect on the response of control
      cells. In conclusion, we have shown that mutant RAS promotes differentiation
      associated cell death in P39 cells by stimulating the activity of PKC, which is
      itself an important regulator of myeloid differentiation. PKC activation, in
      turn, powerfully synergizes with the PKC-independent action of ATRA. This work
      identifies a possible explanation for the ability of this oncogene to promote
      myeloid differentiation of hematopoietic cells. Clinically, it raises the
      possibility that although leukemias expressing mutant RAS may not show an altered
      response to cytotoxic agents, they may show enhanced sensitivity to
      differentiation therapy with ATRA.

PMID- 9581850
TI  - Absence of a radiation-induced first-cycle G1-S arrest in p53+ human tumor cells
      synchronized by mitotic selection.
AB  - It is well known that normal human diploid fibroblasts undergo a significant, p53
      dependent arrest in the G1 phase of the cell cycle after exposure to ionizing
      radiation. The presence and magnitude of a G1 arrest in human tumor cell lines,
      however, has been controversial, particularly in cells derived from solid tumors
      and irradiated during exponential growth. To examine this question more
      precisely, we synchronized cells by mitotic selection and irradiated them in very
      early G1 prior to any of the described G1 checkpoints. Progression of cells from
      G1 into the S phase was monitored by autoradiographic measurement of cumulative
      labeling indices and by flow cytometric analysis. Three different human tumor
      cell lines confirmed as expressing normal p53 function were examined, i.e., lines
      derived from an adenocarcinoma of the colon (RKO), a breast cancer (MCF-7), and a
      squamous cell carcinoma (SCC61). Following irradiation with 4-8 Gy, there was a
      transient delay in progression from G1 into S phase, lasting approximately 2 h,
      and in two of the three cell lines (RKO and MCF-7), a small fraction of cells (5
      8%) never entered the first S phase. Although there was no evidence for a
      prolonged G1 arrest, the expected G2 delay was observed in all three cell lines.
      When irradiated RKO cells were resynchronized at the next mitosis, approximately
      30% of the cells did not enter the second S phase. This latter finding is
      consistent with earlier reports on the kinetics of radiation-induced reproductive
      failure in mammalian cells. These results indicate that cells derived from human
      solid tumors that express normal p53 may respond to irradiation quite differently
      than do normal cells in terms of G1 checkpoint control.

PMID- 9581852
TI  - The use of biochemical markers in ischaemic heart disease: prefactory remarks.
AB  - There has been a lack of rigour in many test assessments. The seven well-accepted
      methodological standards, which are often ignored, are: (1) a suitable spectrum
      of the investigated population; (2) demarcation of significant clinical sub
      groups; (3) avoidance of verification bias; (4) avoidance of review bias; (5)
      indices of test performance reported with their confidence intervals; (6)
      adequate handling of indeterminate results; (7) adequate test reproducibility.
      Additionally, rule-in and rule-out decision thresholds should be reported related
      to time after infarction. These decision thresholds are dependent on the
      particular methodology in use and confusion can, and does, result when comparing
      a value obtained with one analyzer with another. There is an urgent need for the
      standardization of analyte calibration. There are eight methodological standards
      for post-infarction prognosis studies. Less than 15% fulfilled these standards in
      a recent study of 766 such reports.

PMID- 9581851
TI  - Elevated cyclins and cyclin-dependent kinase activity in the rhabdomyosarcoma
      cell line RD.
AB  - An important early event in the differentiation of skeletal muscle cells is exit
      from the cell cycle, after which full expression of the muscle phenotype occurs.
      Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, expresses a number of
      muscle-specific proteins, including MyoD; however, these cells fail to arrest or
      differentiate when cultured in differentiation medium (DM). To determine the
      basis for the failure of RMS cells to differentiate or arrest, we studied the
      molecular response of the embryonal RMS cell line, RD, to culture in DM. Under
      these conditions, the retinoblastoma protein (RB) was primarily in the
      hyperphosphorylated state. This is in contrast to myoblasts cultured in DM, in
      which the hypophosphorylated form of RB is exclusively present. Measurements of
      the expression and activities of cyclin-dependent kinases (cdks) cdk2 and cdk4
      indicated that RD cells maintained higher levels than do myoblasts, and the
      activity and abundance of these proteins did not significantly decrease upon
      culture in DM in RD cells, as they did in myoblasts. Similarly, elevated
      expression of cyclins D1, E, and A was observed in RD cells. Interestingly, cdk
      inhibitors are expressed in RD cells, with p16ink4 expression markedly elevated
      relative to myoblasts. Ectopic expression of p21cip1, p16ink4, or p27kip1 caused
      a growth arrest of RD cells but not detectable expression of a myogenic marker.
      Furthermore, a constitutively active RB protein could also inhibit the growth of
      RD cells without inducing myogenic differentiation. Taken together, these data
      suggest that the elevated levels of cdk2 and/or cdk4 observed in RD cells
      contribute to the inability of RD cells to growth arrest when cultured in DM but
      that these activities alone are not responsible for the failure of RD cells to
      differentiate.

PMID- 9581853
TI  - Analytical and clinical evaluation of new diagnostic tests for myocardial damage.
AB  - As with any new test, novel cardiac markers must meet basic analytical and
      clinical performance issues. For sensitivity and specificity, it is important to
      know what protein forms are released into blood after injury, and which of these
      forms are measured by the assays in question. When commercial tests become
      available, the choice of the measurement platform will be important in the timely
      delivery of results. The cut-off concentration used is also important, and
      requires careful selection of the patient groups to be studied. If the intent of
      the marker is to be used to diagnose acute myocardial infarction (AMI), data from
      normal subjects should not be included. However, low cut-off limits can be useful
      for detection of minor myocardial injury if the new assay is highly sensitive and
      specific. New tests are needed in the area of early diagnosis of AMI, detection
      of reinfarction or myocardial extension after AMI, risk stratification of
      patients with unstable angina, and therapeutic monitoring of patients with
      congestive heart failure. The most promising new markers are glycogen
      phosphorylase BB, free fatty acid binding protein, and brain natriuretic peptide.

PMID- 9581854
TI  - Diagnostic application of CK-MB mass determination.
AB  - Recent advances in analytic techniques have increased the diagnostic value of
      creatine kinase MB (CK-MB), enabling earlier and more sensitive results. The CK
      MB mass immunoassays, that utilise the monoclonal anti-CK-MB in conjunction with
      anti-M or anti-B antibodies, are able to measure accurately small changes during
      the early hours after myocardial infarction (MI). CK-MB has two main limitations
      in diagnosing MI neither of which however undermines its established clinical
      value: CK-MB is not perfectly specific to cardiac injury, with increase occurring
      also during massive musculoskeletal injury; furthermore, the early release
      pattern of CK-MB limits its value for the late MI diagnosis. For the foreseeable
      future evidence is compelling for greater access to rapid testing capabilities in
      emergency situations, using protocols incorporating CK-MB mass evaluation
      together with other biochemical markers, i.e. myoglobin and troponins.

PMID- 9581855
TI  - Early diagnosis of myocardial infarction with MB CK isoforms.
AB  - Over 5 million patients with chest pain present annually to the ER in the US but
      only 10% will have infarction with < 50% identified by ECG. Early diagnosis of
      infarction in the ER to triage provides more appropriate and early therapy, less
      unnecessary use of CCU, and is more cost effective. A rapid automated MB CK
      isoform assay (25 min) was evaluated in a prospective study of 1110 patients
      presenting to the ER with chest pain. This assay was shown to have a sensitivity
      of 96% and specificity of 93% to diagnose infarction within 6 h of onset of chest
      pain. In 92% the diagnosis was confirmed within 1 h of arrival at the ER. Similar
      sensitivity and specificity for total MB CK, troponin T, and troponin I required
      16 h from onset of pain. Thus, MB CK isoforms provide a rapid diagnosis early
      after onset of infarction and have the requisite sensitivity and specificity for
      triaging patients in the ER.

PMID- 9581856
TI  - Troponin T: a sensitive and specific diagnostic and prognostic marker of
      myocardial damage.
AB  - Cardiac troponin T (cTnT) in serum is a highly sensitive and specific marker for
      myocardial damage. Quantitative immunoassays take 9 min. A rapid test (TropT,
      CardiacT) using plasma detects cTnT concentrations above 0.10 microg/l within 15
      min. Both assays are specific for the cardiac isoform. In a study using the
      maximal values from serial sampling in 502 infarction-suspected patients, we
      found a diagnostic sensitivity for non-Q- and Q-wave infarctions of 100%, with a
      specificity of 99%. cTnT has been shown to be a powerful prognostic marker for
      risk stratification in acute coronary syndromes. In 30-40% of patients with
      unstable angina, cTnT > or = 0.10 microg/l detects minor myocardial damage (MMD)
      with poor prognosis. False positives may be found in certain skeletal muscle
      diseases, such as polymyositis and Duchenne's muscular dystrophy. Constantly
      increased values in renal failure may be due to uremic cardiomyositis. Even in
      uremia, a rapid increase of cTnT will indicate acute myocardial damage. We
      propose a diagnostic strategy based on timed, parallel determinations of
      myoglobin + cTnT.

PMID- 9581857
TI  - Assessment of left ventricular function using serum cardiac troponin I
      measurements following myocardial infarction.
AB  - The prognosis and extent of injury to the myocardium have previously been
      assessed by increased serum creatine kinase (CK) MB levels. We report findings
      from 39 consecutive, acute myocardial infarction (AMI) patients presenting 4.5 h
      (range, 0.7-12.1 h) after the onset of chest pain. We compared CK MB mass (upper
      reference limit, 5.0 ng/ml) and cardiac troponin I (cTnI; upper reference limit,
      0.8 ng/ml) (Stratus II, Dade International) in serial serum specimens obtained
      over 36 h after chest pain from AMI patients; within 6 h after onset of chest
      pain. While the appearance of the kinetics of CK MB and cTnI were similar during
      the initial 24 h following the onset of chest pain, cTnI was increased
      significantly (p < 0.05) over CK MB after 9 to 12 h. Half-life determinations
      (mean+/-S.D.) in 22 of the 39 AMI patients demonstrated a significantly (p <
      0.01) shorter half-life in non-Q-wave infarcts [t1/2 6.8 h (+/-5.6)] vs. Q-wave
      infarcts [t1/2 20.4 h (+/-10.7)]. Further serial time versus marker (mean+/-S.D.)
      results were significantly correlated (p < 0.001, r = 0.66). Sixteen of twenty
      patients assessed by echocardiography had an abnormal left ventricular ejection
      fraction (LVEF); mean 37.6 (S.D. 15.2)%, ranging from 15.4 to 67.6%. LVEF was
      significantly and inversely correlated to peak CK MB (r = .50, p = 0.03), as well
      as to peak cTnI (r = 0.46, p = 0.04). Based on these findings, cTnI shows
      excellent promise as a useful marker of infarct size, for the assessment of left
      ventricular function, and may potentially replace CK MB as the cardiac-specific
      marker for AMI detection.

PMID- 9581858
TI  - Diagnostic strategies using myoglobin measurement in myocardial infarction.
AB  - Myoglobin, a low molecular-weight heme protein (17800 D) present in both cardiac
      and skeletal muscle, is an old test with new perspectives. Advantages and
      disadvantages of myoglobin determination are well known. Myoglobin is the
      earliest known, commercially available, biochemical marker of acute myocardial
      infarction (AMI) and its rapid kinetics make it an early, good marker of
      reperfusion. However, since myoglobin is present in both skeletal and cardiac
      muscle, any damage to these muscle types results in its release into blood. Serum
      myoglobin levels are falsely elevated in conditions unrelated to AMI as skeletal
      muscle and neuromuscular disorders, renal failure, intramuscular injection,
      strenuous exercise, and after several toxins and drugs intake. New strategies for
      myoglobin measurement may resolve this limitation. These strategies include both
      the combined measurement of myoglobin and a skeletal specific marker (carbonic
      anhydrase III) or a cardiac specific marker (troponin I), as well as the
      myoglobin evaluation on serial samples. In particular, the diagnostic algorithm
      based on the combined measurement of myoglobin and troponin I, assuring a
      satisfactory analytical turnaround time, significantly improves the diagnostic
      efficiency of laboratory assessment of suspected AMI patients, allowing the
      successive monitoring of coronary reperfusion.

PMID- 9581859
TI  - Glycogen phosphorylase isoenzyme BB to diagnose ischaemic myocardial damage.
AB  - Glycogen phosphorylase isoenzyme BB (GPBB) is a key enzyme of glycogenolysis. Its
      degree of association with the sarcoplasmatic reticulum glycogenolysis complex
      depends essentially on the metabolic state of the myocardium. With the onset of
      tissue hypoxia, when glycogen is broken down, GPBB is converted from a
      structurally bound into a cytoplasmatic form. Considerable amounts of GPBB are
      only found in human heart and brain. In the first clinical studies GPBB was the
      most sensitive marker for the diagnosis of acute myocardial infarction within 4 h
      of chest pain onset. GPBB also increases early in patients with unstable angina
      and reversible ST-T alterations in the resting electrocardiogram at hospital
      admission, which could be useful for risk stratification. GPBB is sensitive for
      the detection of perioperative ischaemic myocardial damage and infarction in
      patients undergoing coronary artery bypass grafting. The diagnostic specificity
      of GPBB in non-traumatic chest pain patients was comparable to creatine kinase
      MB. These results indicate that GPBB is a sensitive marker for ischaemic
      myocardial damage.

PMID- 9581860
TI  - Fatty acid-binding protein and the early detection of acute myocardial
      infarction.
AB  - Fatty acid-binding protein (FABP) is a newly introduced plasma marker of acute
      myocardial infarction (AMI). The plasma kinetics of FABP (15 kD) closely resemble
      those of myoglobin (18 kD) in that elevated plasma concentrations are found
      within 3 h after AMI and return to normal generally within 12 to 24 h. This makes
      both myoglobin and FABP useful biochemical markers for the early assessment or
      exclusion of AMI. The myocardial tissue content of FABP (0.5 mg/g) is about five
      fold lower than that of myoglobin (2.5 mg/g), but the reference plasma
      concentration of FABP (ca. 2 microg/l) is about 15-fold lower than that of
      myoglobin (ca. 32 microg/l), together suggesting a superior performance of FABP
      for the early detection of AMI. Indeed, in a study including blood samples from
      83 patients with confirmed AMI, taken immediately upon admission to the hospital
      (< 6 h after AMI), the diagnostic sensitivity was significantly greater for FABP
      (78%, confidence interval 67-87%) than for myoglobin (53%, CI 40-64%) (P < 0.05).
      In addition, the differences in contents of myoglobin and FABP in heart and
      skeletal muscles and their simultaneous release upon muscle injury allow the
      plasma ratio of myoglobin/FABP to be applied for discrimination of myocardial
      (ratio 4-5) from skeletal muscle injury (ratio 20-70). Rapid and sensitive
      immunochemical assay systems for FABP in plasma are now being developed and soon
      will enable the introduction of this marker in clinical practice.

PMID- 9581861
TI  - The use of biochemical markers in ischaemic heart disease: summary of the
      roundtable and extrapolations.
AB  - Acceptable biochemical markers of ischaemic heart disease are now considered to
      include myoglobin, CK-MB isoforms, CK-MB, and cardiac troponins T and I. AST
      (SGOT), total LD and LD isoenzymes, and total CK activity measurements are
      regarded as obsolete for this purpose. All acceptable biochemical markers must be
      available, if required, with a turnaround time of < 20 min. Such a service can
      either be provided by quantitative assays in a well-equipped laboratory or by
      qualitative point-of-care (bedside) devices (except for the CK-MB isoform assay)
      which can also be used in patients' homes and ambulances. There is, however, a
      pressing need for the careful side-by-side assessment of the relative merits of
      each of these biochemical markers to permit definitive conclusions about their
      future usage. A particular problem is the lack of primary standards for CK-MB and
      troponin I assays. The sensitivity of the initial ECG is about 50% for detecting
      myocardial damage; thus the use of biochemical markers may contribute to the
      early diagnosis and monitoring of thrombolytic therapy and these possible
      applications are examined. In addition, biochemical markers are presently the
      gold standard for the diagnosis of minor myocardial damage. There is now good
      evidence that biochemical markers, particularly the cardiac troponins, have a
      prognostic function in ischaemic heart disease although such findings pose
      unanswered clinical management questions. At the same time, it is recognized that
      there is often no need at all for the use of any biochemical marker when the
      clinical diagnosis is unequivocal, other than for prognosis, monitoring
      thrombolytic therapy, or diagnosing reinfarction.

PMID- 9581863
TI  - Formation of the 67-kDa laminin receptor by acylation of the precursor.
AB  - Even though the involvement of the 67-kDa laminin receptor (67LR) in tumor
      invasiveness has been clearly demonstrated, its molecular structure remains an
      open problem, since only a full-length gene encoding a 37-kDa precursor protein
      (37LRP) has been isolated so far. A pool of recently obtained monoclonal
      antibodies directed against the recombinant 37LRP molecule was used to
      investigate the processing that leads to the formation of the 67-kDa molecule. In
      soluble extracts of A431 human carcinoma cells, these reagents recognize the
      precursor molecule as well as the mature 67LR and a 120-kDa molecule. The
      recovery of these proteins was found to be strikingly dependent upon the cell
      solubilization conditions: the 67LR is soluble in NP-40-lysis buffer whereas the
      37LRP is NP-40-insoluble. Inhibition of 67LR formation by cerulenin indicates
      that acylation is involved in the processing of the receptor. It is likely a
      palmitoylation process, as indicated by sensitivity of NP-40-soluble extracts to
      hydroxylamine treatment. Immunoblotting assays performed with a polyclonal serum
      directed against galectin3 showed that both the 67- and the 120-kDa proteins
      carry galectin3 epitopes whereas the 37LRP does not. These data suggest that the
      67LR is a heterodimer stabilized by strong intramolecular hydrophobic
      interactions, carried by fatty acids bound to the 37LRP and to a galectin3 cross
      reacting molecule.

PMID- 9581862
TI  - Potent interaction of histamine and polyamines at microsomal cytochrome P450,
      nuclei, and chromatin from rat hepatocytes.
AB  - Histamine and polyamines have been implicated in the mediation of cell
      proliferation. Our previous work linked the growth-modulatory effects of
      histamine with its binding to intracellular sites in microsomes and nuclei of
      various tissues. In this study, we identify cytochrome P450 enzymes as a major
      component of microsomal intracellular sites in hepatocytes and demonstrate that
      polyamines compete with high affinity for histamine binding to them. Spectral
      measurement of histamine binding to P450 in liver microsomes resolved high and
      intermediate affinity binding sites (Ks1 = 2.4 +/- 1.6 microM; Ks2 = 90 +/- 17
      microM) that corresponded to microsomal binding sites (Kd1 = 1.0 +/- 0.9 microM;
      Kd2 = 57 +/- 13 microM) resolved by 3H-histamine binding; additional low affinity
      (Kd3 approximately 3 mM), and probably physiologically irrelevant, sites were
      resolved only by 3H-histamine radioligand studies. As determined spectrally,
      treatment of microsomes with NADPH/carbon monoxide decreased histamine binding to
      P450 by about 90% and, as determined by 3H-histamine binding, abolished the high
      affinity sites and reduced by 85% the number of intermediate sites. Spermine
      competed potently for 3H-histamine binding: in microsomes, Ki = 9.8 +/- 5.8
      microM; in nuclei, Ki = 13.7 +/- 3.1 microM; in chromatin, Ki = 46 +/- 33 nM.
      Polyamines inhibited the P450/histamine absorbance complex with the rank order of
      potency: spermine > spermidine >> putrescine. In contrast, histamine did not
      compete for 3H-spermidine binding in nuclei or microsomes, suggesting that
      polyamines modulate histamine binding allosterically. We propose that certain
      P450 isozymes that modulate gene function by controlling the level of oxygenated
      lipids, represent at least one common intracellular target of growth-regulatory
      endogenous bioamines and, as shown previously, of exogenous growth-modulatory
      drugs including antiestrogens, antiandrogens, and certain antidepressants and
      antihistamines.

PMID- 9581864
TI  - Tiludronate inhibits interleukin-6 synthesis in osteoblasts: inhibition of
      phospholipase D activation in MC3T3-E1 cells.
AB  - In previous studies, we have reported that PGF2alpha stimulates phosphoinositide
      hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase
      D through heterotrimeric GTP-binding protein in osteoblast-like MC3T3-E1 cells,
      and that PGF2alpha and PGE1 induce interleukin-6 (IL-6) synthesis via activation
      of protein kinase C and protein kinase A, respectively. In the present study, we
      investigated the effect of tiludronate, a bisphosphonate known to inhibit bone
      resorption, on the PGF2alpha- and PGE1-induced IL-6 synthesis in these cells.
      Tiludronate significantly suppressed the PGF2alpha-induced IL-6 secretion in a
      dose-dependent manner in the range between 0.1 and 30 microM. However, the IL-6
      secretion induced by PGE1 or (Bu)2cAMP was hardly affected by tiludronate. The
      choline formation induced by PGF2alpha was reduced by tiludronate dose
      dependently in the range between 0.1 and 30 microM. On the contrary, tiludronate
      had no effect on PGF2alpha-induced formation of inositol phosphates. Tiludronate
      suppressed the choline formation induced by NaF, known as an activator of
      heterotrimeric GTP-binding protein. However, tiludronate had little effect on the
      formation of choline induced by TPA, a protein kinase C activator. Tiludronate
      significantly inhibited the NaF-induced IL-6 secretion in human osteoblastic
      osteosarcoma Saos-2 cells. These results strongly suggest that tiludronate
      inhibits PGF2alpha-induced IL-6 synthesis via suppression of phosphatidylcholine
      hydrolyzing phospholipase D activation in osteoblasts, and that the inhibitory
      effect is exerted at the point between heterotrimeric GTP-binding protein and
      phospholipase D.

PMID- 9581865
TI  - High affinity MAR-DNA binding is a common property of murine and human mutant
      p53.
AB  - We recently reported that murine MethA mutant but not wild-type p53 specifically
      binds to MAR-DNA elements (MARs) with high affinity. Here we show that this DNA
      binding activity is exerted not only by MethA mutant p53 but also by other murine
      mutant p53 proteins isolated from the transformed murine BALB/c cell lines 3T3tx
      and T3T3 and differing in their conformational status. High affinity MAR-DNA
      binding was not restricted to the Xbal-IgE-MAR-DNA fragment from the murine
      immunoglobulin heavy chain gene enhancer locus [Cockerill et al. (1987): J Biol
      Chem 262:5394-5397] used in previous studies, as MethA p53 also specifically
      interacted with other A/T-rich bona fide MARs. Not only murine but also human
      mutant p53 proteins carrying the mutational hot spot amino acid exchanges 175Arg-
      >His, 273Arg-->Pro, or 273Arg-->His bound to the Xbal-IgE-MAR-DNA fragment. We
      therefore conclude that high affinity MAR-DNA binding is a property common to a
      variety of mutant p53 proteins.

PMID- 9581866
TI  - Butyrate analogue, isobutyramide, inhibits tumor growth and time to androgen
      independent progression in the human prostate LNCaP tumor model.
AB  - Progression to androgen independence remains the main obstacle to improving
      survival and quality of life in patients with advanced prostate cancer. Induction
      of differentiation may serve as a rational basis for prevention of progression to
      androgen independence by modulating gene expression activated by castration or
      upregulated during androgen-independent progression. The objectives of this study
      were to characterize the in vitro effects of sodium butyrate on human prostate
      cancer cell growth, PSA gene expression, and differentiation in the LNCaP tumor
      model and to determine whether tumor progression in vivo is delayed by
      isobutyramide, an orally bioavailable butyrate analogue with a longer half-life.
      The effects of isobutyramide on LNCaP tumor growth and serum PSA levels in both
      intact and castrate male mice were compared to controls. At concentrations >1 mM,
      butyrate induced dose-dependent changes towards a more differentiated phenotype,
      G1 cell cycle arrest, and an 80% decrease in LNCaP cell growth rates. PSA gene
      expression was increased threefold by butyrate, indicative of differentiation
      enhanced gene expression. The half-life of isobutyramide in athymic mice was
      determined by gas chromatography to be 4 h. During a 4 week period in intact
      placebo mice, tumor volume and serum PSA increased 4.1- and 6.6-fold,
      respectively, compared to twofold and 2.7-fold increases in tumor volume and
      serum PSA in intact-treated mice. During a 7 week period in castrate-placebo
      mice, tumor volume and serum PSA levels increased 2.4-fold and fourfold,
      respectively, compared to a 50% reduction in tumor volume and a twofold increase
      in serum PSA above nadir levels in castrate mice treated with adjuvant
      isobutyramide. Isobutyramide treatment induced pronounced morphological changes
      in LNCaP tumor cells, with loss of defined nucleoli and dispersion of chromatin
      distribution. LNCaP tumor PSA mRNA levels actually increased threefold,
      indicative of differentiation-enhanced gene expression. This study demonstrates
      that butyrate causes LNCaP cell cycle arrest and increased PSA gene expression,
      both indicative of differentiation. The combination of castration and adjuvant
      isobutyramide was synergistic in delaying tumor progression. Decreased tumor cell
      proliferation and increased PSA gene expression induced by isobutyramide results
      in disconcordant changes in serum PSA and tumor volume and reduces the utility of
      serum PSA as a marker of response to therapy.

PMID- 9581867
TI  - Estrogen modulation of osteoblastic cell-to-cell communication.
AB  - Two osteoblastic cell populations, calvarial and marrow stromal cells, were
      exposed to estrogen derivatives in vitro. The hormonal effect was monitored by
      following intracellular Ca+2 levels [Ca+2]i and gap-junction communication. We
      measured fast changes in intracellular Ca+2 levels in response, of these cells,
      to the steroid hormones. The changes were dose dependent revealing maximal
      activity at 100 pM by 17-beta-Estradiol and 1 nM by estradiol-CMO. Additionally,
      the effect of estrogen, on functional coupling of the cells, was measured using
      fluorescence dye migration and counting the number of neighboring cells coupled
      by gap junctions. An uncoupling effect was demonstrated in response of these
      cells to estrogen treatment. The quick stereospecific effect was achieved in the
      presence of 17-beta-estradiol but not in the presence of 17-alpha-estradiol.
      These results suggest the involvement of plasma membrane receptors in addition to
      the already known nuclear receptors in transducing the hormone effects in the
      osteoblastic cells.

PMID- 9581868
TI  - TGF-beta1 modifications in nuclear matrix proteins of osteoblasts during
      differentiation.
AB  - Nuclear matrix protein (NMP) composition of osteoblasts shows distinct two
      dimensional gel electrophoretic profiles of labeled proteins as a function of
      stages of cellular differentiation. Because NMPs are involved in the control of
      gene expression, we examined modifications in the representation of NMPs induced
      by TGF-beta1 treatment of osteoblasts to gain insight into the effects of TGF
      beta on development of the osteoblast phenotype. Exposure of proliferating fetal
      rat calvarial derived primary cells in culture to TGF-beta1 for 48 h (day 4-6)
      modifies osteoblast cell morphology and proliferation and blocks subsequent
      formation of mineralized nodules. Nuclear matrix protein profiles were very
      similar between control and TGF-beta-treated cultures until day 14, but
      subsequently differences in nuclear matrix proteins were apparent in TGF-beta
      treated cultures. These findings support the concept that TGF-beta1 modifies the
      final stage of osteoblast mineralization and alters the composition of the
      osteoblast nuclear matrix as reflected by selective and TGF-beta-dependent
      modifications in the levels of specific nuclear matrix proteins. The specific
      changes induced by TGF-beta in nuclear matrix associated proteins may reflect
      specialized mechanisms by which TGF-beta signalling mediates the alterations in
      cell organization and nodule formation and/or the consequential block in
      extracellular mineralization.

PMID- 9581870
TI  - Src protein and tyrosine-phosphorylated protein profiles in marrow stroma during
      osteogenic stimulation.
AB  - Src protein is essential for the regulation of bone turnover primarily via bone
      resorption because it is required in osteoclast differentiation and function. We
      followed temporal changes of Src protein abundance in marrow stromal cells
      induced to mineralize by dexamethasone (DEX), growth in cold temperature, or
      both. Given the tyrosine kinase function of Src and its numerous substrates,
      profiles of phosphotyrosine-containing proteins were followed as well. On day 11
      of stimulation, specific alkaline phosphatase (ALP) activity at 30 degrees C
      decreased under DEX relative to 37 degrees C cultures, in accord with increased
      cell counts. Mineralization per well under DEX increased by 25% at 37 degrees C,
      whereas at 30 degrees C it increased by more than threefold regardless of the DEX
      stimulation. At 30 degrees C, on a per cell basis mineralization increased 2.5
      and 3 times with and without DEX, respectively. Cultures at 37 degrees C showed a
      general drop per cell of many phosphotyrosine-containing proteins on day 3
      relative to days 1 and 2 in both DEX-stimulated and nonstimulated cultures;
      several proteins did recover (recuperate) thereafter. On days 1 and 2, the
      phosphotyrosine signal was higher in several proteins under DEX stimulation; this
      trend became inverted after day 3. The changes in abundance per cell of Src
      protein (pp60src) followed a similar trend, and in addition a truncated Src
      molecule, p54/52src, was detected as a putative cleavage product presumably
      representing its carboxy terminus. The pp60src was most abundant, relative to its
      truncated product, in day 7 nonstimulated cultures, whereas under DEX stimulation
      the truncated species pp54/52src showed the highest relative abundance on days 7.
      At 30 degrees C, DEX stimulation accentuated the increase in Src protein on day
      3, showed no change on day 7, and returned to increase Src protein on day 10.
      Potassium ionophorvalinomycin, considered to select against mineralizing
      osteoprogenitors at 30 degrees C, showed on day 10 in the absence of DEX a
      relative increase in truncated Src protein compared to both DEX-stimulated and
      nonstimulated cultures in the absence of valinomycin. On day 7 of DEX
      stimulation, the presence of valinomycin resulted in low p54/52src. Among
      phosphotyrosine-containing proteins, a 32-34 kDa band, as yet unidentified,
      showed the most concordant changes with mineralization induction. P32-34
      decreased by DEX on days 2 and 8 and increased by low temperature alone or
      combined with DEX on day 3. On day 7, p32-34 did not change under DEX, but
      valinomycin selected cells with less phoshpotyrosine-containing p32-34. Taken
      together, high Src abundance at the start of osteogenic induction followed by a
      decrease 1 week later is probably related to energy metabolism-dependent
      induction of mineralization. This is in temporal accord with the increase in Src
      truncation and fluctuation in mitochondrial membrane potential (which affects
      mineralization). The reported binding of amino-terminal Src oligopeptide to p32
      ADP/ATP carrier in the mitochondrial inner membrane raises the question of its
      possible involvement in mitochondria-regulated mineralization.

PMID- 9581869
TI  - Mammalian protein homologous to VAT-1 of Torpedo californica: isolation from
      Ehrlich ascites tumor cells, biochemical characterization, and organization of
      its gene.
AB  - Recently, interest has focused on the human gene encoding the putative protein
      homologous to VAT-1, the major protein of the synaptic vesicles of the electric
      organ of the Pacific electric ray Torpedo californica, after it has been
      localized on chromosome locus 17q21 in a region encompassing the breast cancer
      gene BRCA1. Chromosomal instability in this region is implicated in inherited
      predisposition for breast and ovarian cancer. Here we describe isolation and
      biochemical characterization of a mammalian 48 kDa protein homologous to the VAT
      1 protein of Torpedo californica. This VAT-1 homolog was isolated from a murine
      breast cancer cell line (Ehrlich ascites tumor) and identified by sequencing of
      cleavage peptides. The isolated VAT-1 homolog protein displays an ATPase activity
      and exists in two isoforms with isoelectric points of 5.7 and 5.8. cDNA was
      prepared from Ehrlich ascites tumor cells, and the murine VAT-1 homolog sequence
      was amplified by polymerase chain reaction and partially sequenced. The known
      part of the murine and the human translated sequences share 97% identity. By
      Northern blots, the size of the VAT-1 homolog mRNA in both murine and human
      (T47D) breast cancer cells was determined to be 2.8 kb. Based on the presented
      data, a modified gene structure of the human VAT-1 homolog with an extended exon
      1 is proposed. VAT-1 and the mammalian VAT-1 homolog form a subgroup within the
      protein superfamily of medium-chain dehydrogenases/reductases.

PMID- 9581871
TI  - Copper stimulates proliferation of human endothelial cells under culture.
AB  - Copper ions stimulate proliferation of human umbilical artery and vein
      endothelial cells but not human dermal fibroblasts or arterial smooth muscle
      cells. Incubation of human umbilical vein endothelial cells for 48 h with 500
      microM CuSO4 in a serum-free medium in the absence of exogenous growth factors
      results in a twofold increase in cell number, similar to the cell number increase
      induced by 20 ng/ml of basic fibroblast growth factor under the same conditions.
      Copper-induced proliferation of endothelial cells is not inhibited by 10% fetal
      bovine serum or by the presence of antibodies against a variety of angiogenic,
      growth, and chemotactic factors including angiogenin, fibroblast growth factors,
      epidermal growth factor, platelet-derived growth factor, tumor necrosis factor
      alpha, transforming growth factor-beta, macrophage/monocyte chemotactic and
      activating factor, and macrophage inflammatory protein-1alpha. Moreover, despite
      the previous observations that copper increased total specific binding of 125I
      angiogenin to endothelial cells, binding to the 170 kDa receptor is not changed;
      hence, the mitogenic activity of angiogenin is not altered by copper. Copper
      induced proliferation, along with early reports that copper induces migration of
      endothelial cells, may suggest a possible mechanism for the involvement of copper
      in the process of angiogenesis.

PMID- 9581872
TI  - PTH-responsive osteoblast nuclear matrix architectural transcription factor binds
      to the rat type I collagen promoter.
AB  - In connective tissue, cell structure contributes to type I collagen expression.
      Differences in osteoblast microarchitecture may account for the two distinct cis
      elements regulating basal expression, in vivo and in vitro, of the rat type I
      collagen alpha1(I) polypeptide chain (COL1A1). The COL1A1 promoter conformation
      may be the penultimate culmination of osteoblast structure. Architectural
      transcription factors bind to the minor groove of AT-rich DNA and bend it,
      altering interactions between other trans-acting proteins. Similarly, nuclear
      matrix (NM) proteins bind to the minor groove of AT-rich matrix-attachment
      regions, regulating transcription by altering DNA structure. We propose that
      osteoblast NM architectural transcription factors link cell structure to promoter
      geometry and COL1A1 transcription. Our objective was to identify potential
      osteoblast NM architectural transcription factors near the in vitro and in vivo
      regulatory regions of the rat COL1A1 promoter. Nuclear protein-promoter
      interactions were analyzed by gel shift analysis and related techniques. NM
      extracts were derived from rat osteosarcoma cells and from rat bone. The NM
      protein, NMP4, and a soluble nuclear protein, NP, both bound to two homologous
      poly(dT) elements within the COL1A1 in vitro regulatory region and proximal to
      the in vivo regulatory element. These proteins bound within the minor groove and
      bent the DNA. Parathyroid hormone increased NP/NMP4 binding to both poly(dT)
      elements and decreased COL1A1 mRNA in the osteosarcoma cells. NP/NMP4-COL1A1
      promoter interactions may represent a molecular pathway by which osteoblast
      structure is coupled to COL1A1 expression.

PMID- 9581873
TI  - CBFa(AML/PEBP2)-related elements in the TGF-beta type I receptor promoter and
      expression with osteoblast differentiation.
AB  - Organization of the transforming growth factor-beta (TGF-beta) type I receptor
      (TRI) promoter predicts constitutive transcription, although its activity
      increases with differentiation status in cultured osteoblasts. Several sequences
      in the rat TRI promoter comprise cis-acting elements for CBFa (AML/PEBP2alpha)
      transcription factors. By gel mobility shift and immunological analyses, a
      principal osteoblast-derived nuclear factor that binds to these sites is CBFa1
      (AML-3/PEBP2alphaA). Rat CBFa1 levels parallel expression of the osteoblast
      phenotype and increase under conditions that promote mineralized bone nodule
      formation in vitro. Fusion of CBFa binding sequence from the TRI promoter to
      enhancer-free transfection vector increases reporter gene expression in cells
      that possess abundant CBFa1, and overexpression of CBFa increase the activity of
      transfected native TRI promoter/reporter plasmid. Consequently, phenotype
      restricted use of cis-acting elements for CBFa transcription factors can
      contribute to the high levels of TRI that parallel osteoblast differentiation and
      to the potent effects of TGF-beta on osteoblast function.

PMID- 9581874
TI  - Multivalent cations depress ligand affinity of insulin-like growth factor-binding
      proteins-3 and -5 on human GM-10 fibroblast cell surfaces.
AB  - The effect of multivalent cations on [125I]-IGF binding to cell-associated IGFBPs
      was investigated using human fibroblasts. The major cell-associated binding site
      for [125I]-IGF-I is IGFBP-3 and for [125I]-IGF-II are IGFBP-3 and IGFBP-5.
      Lanthanum and chromium did not affect either [125I]-IGF-I or [125I]-IGF-II
      binding to cell-associated IGFBPs. By contrast, zinc (Zn2+), gold (Au3+), and
      cadmium (Cd2+) depressed binding of both ligands. Ligand binding resulted in
      nonlinear Scatchard plots. Assuming a pre-existent asymmetric model with high-
      (K[aHi]) and low- (K[aLo]) affinity sites, Zn2+ lowered both K(aHi) and K(aLo).
      Au3+ eliminated K(aHi). Assuming that the nonlinear plots were caused by ligand
      induced negative cooperativity, Zn2+ and Cd2+ lowered both Ke and Kf (affinity of
      unoccupied and saturated IGFBPs, respectively). Au3+ eliminated Ke and reduced
      Kf. Zn2+ was active at serum levels in lowering IGF binding. Zinc, gold, and
      cadmium bind to similar regions within proteins (a zinc-binding motif) indicating
      similar mechanisms of action. A zinc-binding motif is present in the IGFBPs, but
      not in the IGFs. We demonstrate for the first time that the trace nutrient zinc
      and related multivalent cations decrease IGF binding to fibroblast-associated
      IGFBPs by lowering the affinity of the IGF-IGFBP interaction.

PMID- 9581875
TI  - The Reproductive Tract and HIV-1 Transmission. Papers presented at the two-day
      interdisciplinary conference. Bethesda, Maryland, USA. February 11-12, 1997.

PMID- 9581876
TI  - Toward an understanding of a vector-free pandemic: the reproductive tract as
      conduit for the explosive global spread of HIV-1 infection.

PMID- 9581877
TI  - Heterosexual transmission of human immunodeficiency virus type 1 (HIV):
      interactions of conventional sexually transmitted diseases, hormonal
      contraception and HIV-1.
AB  - The interactions between HIV-1 and other viral sexually transmitted infections
      (STI) are complex. The presence of ulcerative and nonulcerative STD increase
      susceptibility of exposed individuals to HIV-1 infection by several folds. In HIV
      1 infected individuals, STD increase genital tract shedding of HIV-1 and enhance
      the infectivity of these individuals. STD have also recently been shown to
      increase plasma viremia either directly or through altering the cytokine milieu,
      which may both increase infectivity and result in more rapid HIV-1 disease
      progression. HIV-1 infection in turn has effects on susceptibility to other STD
      as well as increasing the serverity of some infections and possibly reducing the
      response to antimicrobial therapy. In addition, other potential risk factors for
      sexual transmission of HIV-1, such as hormonal contraception in women and lack of
      circumcision in men, may operate partly through effects on enhancing
      susceptibility to STD. The mutual enhancement of transmission of HIV-1 and other
      STD that has fueled HIV-1 epidemics worldwide, offers the opportunity for
      intervention. The effectiveness of this approach has recently been demonstrated
      in a trial in Mwanza, Tanzania, where provision of effective treatment for STD
      resulted in a 40% decline in HIV-1 incidence. The implementation of effective STD
      management may do much to slow the spread of HIV-1.

PMID- 9581878
TI  - Prevalence and correlates of HIV type 1 shedding in the female genital tract.
AB  - Heterosexual transmission is the predominant mode of transmission of HIV-1 in
      most of the world. Factors correlated with viral shedding from the female
      reproductive tract (and thus infectivity of women) are discussed in this review.
      Hormonal contraceptive use, cervical ectopy, pregnancy, abnormal cervical and
      vaginal discharge, and CD4 lymphocyte depletion have been associated with
      increased HIV-1 shedding in women; however, findings vary between studies.
      Prevalence and correlates of cervicovaginal HIV-1 shedding in larger published
      studies are discussed and potential mechanisms for observed associations are
      reviewed.

PMID- 9581879
TI  - The vaginal microbial ecosystem and resistance to HIV.

PMID- 9581880
TI  - Urological manifestations of HIV infection.
AB  - HIV-1 disease is associated with many infectious and neoplastic complications.
      This is particularly true of the genitourinary tract, where high rates of renal
      disease, neoplasms, voiding and erectile dysfunction, hematuria, opportunistic
      genitourinary infections, and epididymo-orchitis are found in HIV-1-infected
      individuals. Recent experience at Ben Taub General Hospital (Houston, TX) shows
      that men requiring admission to the urologic service for treatment of
      genitourinary disorders have high rates of HIV-1 seropositivity, particularly in
      the setting of epididymo-orchitis, where 21 of 106 (20%) were found to be HIV-1
      infected. These men were significantly more likely to require surgical treatment
      and to harbor resistant bacteria in infected tissues. Importantly, for 15 of 21
      HIV-1-infected men, epididymo-orchitis was the first clinical manifestation of
      HIV-1 disease, and 6 were first found to be HIV-1 seropositive during that
      admission. Our experience illustrates the critical importance of screening for
      HIV-1 infection in the setting of genitourinary disease.

PMID- 9581881
TI  - Factors associated with changes in HIV shedding in semen.
AB  - The efficiency and duration of transmissibilty of HIV seems to be highly variable
      and dependent on a number of factors related to both the donor and the recipient
      as well as characteristics intrinsic to the virus itself. Some of the factors
      likely to be important in sexual transmission of HIV include stage of disease,
      antiretroviral therapy, and concomitant systemic or mucosal infections, including
      sexually transmitted diseases. This paper describes recent work from our group in
      each of these areas.

PMID- 9581882
TI  - Human immunodeficiency virus in semen arises from a genetically distinct virus
      reservoir.
AB  - The reservoir of human immunodeficiency virus (HIV) in semen is unknown. Several
      lines of evidence suggest that semen HIV may not arise from the same reservoir of
      infection as peripheral blood. If true, the viral burden in the two compartments
      could be qualitatively and quantitatively different, a scenario of potentially
      profound significance for the design of effective strategies of treatment,
      disease monitoring, and infection containment. We report here that the ratio of
      infected to uninfected leukocytes in ejaculated semen specimens is highly
      discordant with paired blood samples, demonstrating that they derive from
      distinct populations of infected cells. In addition, infectious HIV was isolated
      from semen cells, but not from blood cells, of an individual on triple
      antiretroviral therapy; the absence of major resistance-conferring mutations in
      the semen virus indicates that it was replicating in isolation from the antiviral
      agents. The compartmentalization of blood and semen infection was further
      supported by genetic analysis of several infectious HIV clones isolated from
      semen cells and peripheral blood cells of another donor not on antiretroviral
      therapy. Protease gene sequence analyses revealed significant divergence of the
      two viral populations. These findings confirm the distinct compartmentalization
      of HIV in the semen of this study cohort, and support the concept that semen HIV
      arises from an isolated reservoir of infection that may function independently in
      the pathobiology of HIV disease.

PMID- 9581883
TI  - Quantitation of mediators of inflammation and immunity in genital tract
      secretions and their relevance to HIV type 1 transmission.

PMID- 9581884
TI  - Mucosal immunity in the female reproductive tract: correlation of
      immunoglobulins, cytokines, and reproductive hormones in human cervical mucus
      around the time of ovulation.
AB  - Mucosal surfaces serve as the portal of entry for many viral, bacterial, and
      parasitic infections. Understanding the immunity at mucosal membranes is
      essential to enhancing protection and decreasing infections. To evaluate the
      humoral and cellular immunity in the female reproductive tract, 15 reproductive
      age women with a history of regular, cyclic monthly menses were recruited for
      this study. The presence of immunoglobulins and cytokines in cervical mucus was
      correlated with the production of reproductive hormones in sera. Cervical mucus
      specimens were collected at each daily visit beginning on cycle day 8 and
      continuing for 5 days postovulation. Volunteers were monitored by daily urinary
      LH testing coupled with transvaginal ultrasonography to ascertain follicular
      collapse. The cervix was washed in sterile saline before aspirating the cervical
      mucus from the cervical canal. Collection volumes ranged between 50 and 800
      microl and were considered to represent the total mucus produced. Estradiol
      displayed the characteristic biphasic pattern with a peak before ovulation and in
      the luteal phase. Both IgG (30 mg/dl) and IgA (15 mg/dl) had a biphasic pattern
      with peak immunoglobulin levels detected 1 day before the estradiol peak and
      increasing again just after ovulation. Peak interleukin 10 (40 pg/ml) levels
      corresponded precisely with estradiol peak levels just before ovulation. Peak
      interleukin 1beta (1.3 ng/ml) levels occurred approximately 1 day before the
      estradiol peak. No apparent pattern in interleukin 6 (150 pg/ml) could be
      ascertained. Our data suggest a correlation between the IgG and IgA
      immunoglobulin levels, interleukin 1beta and interleukin 10, in the female
      reproductive tract and estradiol levels in the circulation. The increase in
      immunoglobulins and cytokines occurs approximately 1 day before the peak
      estradiol production before ovulation. These data suggest a role for cytokines
      and hormones in the regulation of reproductive tract immunity.

PMID- 9581885
TI  - The mucosal immune system in the human female reproductive tract: potential
      insights into the heterosexual transmission of HIV.
AB  - Using isolated cell suspensions and in situ techniques, we have partially
      characterized the organization, functional capacity, and sex hormone regulation
      of the mucosal immune system in the human female reproductive tract. Isolated
      cells suspensions have been used to demonstrate that the uterus contains antigen
      presenting cells that are functionally able to present antigen to autologous
      tetanus toxoid-specific T cells. Immunophenotypic analyses of the female
      reproductive tract by three-color immunofluorescent staining has been used to
      show that lymphoid aggregates, which are absent in postmenopausal women, develop
      in the uterine endometrium during the menstrual cycle in premenopausal women.
      Lymphoid aggregates are composed of a B lymphocyte core surrounded by numerous
      CD8+CD4- T lymphocytes and an outer halo of macrophages. Macrophages, CD4+ and
      CD8+ T cells, and CD56+ NK cells are distributed throughout the uterine
      endometrium. In contrast, the Fallopian tube, cervix, and vagina, which lack
      lymphoid aggregates, contain CD8+ and CD4+ T cells as well as macrophages. The
      female reproductive tract has also been analyzed for the presence of antigen
      independent CD3+ T lymphocyte cytolytic function by an anti-CD3 MAb-mediated
      redirected lysis assay. High levels of CD3+ T lymphocyte cytolytic activity were
      demonstrated in cervix and vagina and independent of stage of the menstrual
      cycle. In the uterus, cytolytic activity changed with endocrine state. In
      postmenopausal women the uterine endometrium had CD3+ T lymphocytes with high
      cytolytic activity, whereas premenopausal women had CD3+ T lymphocytes with
      moderate cytolytic potential during the proliferative phase to low/no cytolytic
      activity during the secretory phase of the menstrual cycle. In studies to
      determine whether the upper reproductive tract could be infected with HIV-1, we
      found on the basis of nef expression and p24 release that epithelial cells from
      the Fallopian tube, and from the uterus and cervix, are infectable. These studies
      demonstrate that the human female reproductive tract is an inductive site for
      immune responses and the cell-mediated immunity is present throughout the female
      reproductive tract. These studies further indicate that the Fallopian tube and
      uterus are potential entry sites for HIV-1 infection and that uterine immune cell
      architecture as well as cytolytic activity are under hormonal control.

PMID- 9581886
TI  - Mucosal phenotype of antiviral cytotoxic T lymphocytes in the vaginal mucosa of
      SIV-infected rhesus macaques.
AB  - CD8+ T lymphocytes are present in the vaginal epithelium and submucosa of women
      and female rhesus macaques. Antiviral cytotoxic T lymphocyte precursors were
      detected in the vaginal intraepithelial lymphocyte (IEL) population of SIV
      infected monkeys. Monoclonal antibodies to adhesion molecules distinguish
      lymphocytes that recirculate through peripheral lymphoid tissues (e.g., L
      selectin) from mucosal lymphocytes that traffic through peripheral blood to the
      gut (e.g., the integrins alpha4beta7 and alphaEbeta7). Cytolytic CD8+ T cell
      lines from either peripheral blood or the vaginal epithelium of SIV-infected
      monkeys were stained with antibodies against these molecules. Three of three
      vaginal epithelial cell lines had the phenotype: alpha4beta7+/alphaEbeta7+/L
      selectin-. Two of three peripheral blood cell lines had this phenotype and the
      other was positive for all three molecules. These results suggest that cytolytic
      vaginal IELs have the same mucosal phenotype as has been described for human and
      murine gut IELs, and that their precursors are destined to traffic through
      peripheral blood and return to the vaginal mucosa.

PMID- 9581887
TI  - Mechanism of monocyte-macrophage-mediated transmission of HIV.
AB  - Observations from our laboratory support the theory that HIV-infected monocyte
      macrophages present in genital tract secretions have an important role in sexual
      transmission of HIV. Light and electron microscopy were used to study the
      behavior of HIV-infected, primary human monocytes. These cells progress on
      surfaces, putting forward a leading pseudopod from which they secrete HIV. When
      added to cultures of CD4-, cervix-derived epithelial cells, monocytes advanced
      between epithelial cells while secreting virus anteriorly. Epithelial cells
      subsequently become productively infected. Infection of epithelia could be
      blocked by sera from HIV-seropositive individuals. These findings support the
      supposition that transmission of HIV may occur via cell-mediated infection of
      intact epithelia. The observations also hint at the possibility that HIV-infected
      monocyte-macrophages in semen or cervical-vaginal secretions could cross intact
      epithelia by passing between epithelial cells. To test this hypothesis supravital
      stained mouse macrophages were inoculated into the vaginas of mice. Four hours
      later numerous stained cells were observed in the connective tissue beneath the
      vaginal epithelium and in the iliac lymph nodes. We speculate that direct
      infection of epithelial cells and/or cell trafficking across epithelia may be
      involved in sexual transmission of HIV.

PMID- 9581888
TI  - SIV replication and the dendritic cell.
AB  - To evaluate the potential involvement of dendritic cells (DCs) in the mucosal
      transmission of HIV-1 we have used a model system of skin-derived DCs to study
      the cell-virus interactions in vitro. More recently we have extended these
      studies to the macaque system to further investigate DCs from a variety of more
      accessible tissues, particularly the mucosae. The DCs isolated from macaque body
      surfaces exhibit an almost identical phenotype and morphology to mature human
      DCs. Both CD4+ and CD8+ T cells are also present in the suspensions isolated from
      these tissues, with some T cells being tightly bound to the DCs. As in the human
      system, the skin-derived DCs support active replication of SIV in collaboration
      with syngeneic skin-derived T cells. Much of the virus is produced by
      multinucleated syncytia. On separation of the cell subsets by cell sorting, it
      was revealed that most active viral replication occurs in the DC-T cell conjugate
      fraction. Virus growth is also detected within the DC-T cell mixtures isolated
      from the nasopharyngeal and vaginal mucosae, but not in those isolated from the
      cervical mucosa. This animal model is being used to further dissect the role of
      DCs in the transmission and pathogenesis of infection with immunodeficiency
      viruses.

PMID- 9581890
TI  - Mucosal transmission of virulent and avirulent lentiviruses in macaques.
AB  - Sexual transmission of human immunodeficiency virus provides an efficient mode
      for virus spread and poses unique challenges to vaccine developers. Host and
      viral factors that affect transmission have been studied by epidemiological
      approaches in the human population, and some of these factors have been modeled
      with experimental infection of nonhuman primates. Basic principles have emerged
      regarding transmission and viral virulence. These ideas may be beneficial for
      designing a safe and effective vaccine.

PMID- 9581889
TI  - Does viral tropism play a role in heterosexual transmission of HIV? Findings in
      the SIV-rhesus macaque model.
AB  - Substantial effort is being directed toward generating vaccines that can prevent
      the heterosexual transmission of HIV-1. If "selection" for specific variants
      during sexual intercourse occurs, then vaccines should be designed to prevent
      transmission of these specific viruses. Using the SIV-rhesus macaque model to
      test the hypothesis that specific HIV genotypes are more efficient at producing
      infection by sexual transmission, it was possible to demonstrate that the
      genotypic determinants that permit SIV or SHIV to produce systemic infection
      differ depending on the route of virus inoculation. This finding supports the
      conclusion that there is selection for viral genotypes during sexual transmission
      of HIV. However, the ability of a virus to grow in rhesus macaque monocyte
      derived macrophages in vitro does not predict the outcome of intravaginal
      inoculation with that virus. We did find that after intravenous inoculation all
      the vaginally transmitting viruses produced plasma antigenemia and high levels of
      plasma viral RNA. In contrast, although the nontransmitting viruses infect rhesus
      macaques after intravenous inoculation, the infection that occurs after
      intravenous inoculation is characterized by a lack of viral antigen in plasma and
      low levels of plasma viral RNA. On the basis of these results, it is clear that
      viruses which are adapted to replicate to high levels in vivo are transmitted by
      vaginal inoculation. This principle may also apply to the transmission of HIV in
      humans.

PMID- 9581891
TI  - The HIV type 1 coreceptor CCR5 and its role in viral transmission and disease
      progression.
AB  - The purified CD4+ lymphocytes of a group of highly exposed but HIV-1-uninfected
      individuals were determined to be less susceptible to infection with multiple non
      syncytium-inducing (NSI) primary isolates of HIV-1 than were CD4+ lymphocytes
      from nonexposed control individuals. This relative resistance to HIV-1 infection
      did not extend to T cell line-adapted or syncytium-inducing (SI) primary viral
      isolates, was restricted by the envelope glycoprotein, and was associated with an
      increased production of the C-C chemokines RANTES, MIP-1alpha, and MIP-1beta. The
      block to replication in CD4+ lymphocytes from two exposed-uninfected subjects was
      at the point of entry, as was the block imposed by the recombinant C-C chemokines
      RANTES, MIP-1alpha, and MIP-1beta. Resistance to infection and the high
      production of beta chemokines were characteristic of every CD4+ lymphocyte clone
      from the exposed-uninfected subjects. We have now identified the mechanism
      underlying this in vitro and in vivo resistance to infection: These individuals
      have inherited a homozygous 32-bp nucleotide deletion (delta32) within the gene
      encoding the coreceptor for primary NSI isolates of HIV-1 (CCR5). This deletion
      encodes a severely truncated and unstable protein that is not expressed on the
      cell surface. This allele is common in the Caucasian population, with a frequency
      of 0.0808, but is not found in people of African or Asian ancestry. To determine
      its role in HIV-1 transmission and disease progression, we analyzed the CCR5
      genotype of 1252 homosexual men enrolled in the Chicago component of the
      Multicenter AIDS Cohort Study (MACS). No infected participant was found to be
      homozygous for the delta32 allele whereas 3.6% of at-risk but uninfected
      Caucasian participants were homozygous, showing the highly protective role of
      this genotype against sexual acquisition of HIV-1. No evidence was found to
      suggest that heterozygotes were protected against HIV-1 infection, but a limited
      protective role against disease progression was noted. The delta32 allele of CCR5
      is therefore an important host factor in HIV-1 transmission and pathogenesis.

PMID- 9581892
TI  - Natural endogenous reverse transcription of HIV type 1.
AB  - Molecular mechanisms by which human lentiviruses, such as human immunodeficiency
      virus type 1 (HIV-1), are sexually transmitted have yet to be fully elucidated.
      It is now demonstrated that endogenous reverse transcription of lentiviruses can
      occur within the intact virion, before infection of target cells. This is a
      biochemically active process and is altered by the microenvironment to which HIV
      1 virions are subjected. Stimulation of endogenous reverse transcription within
      virion particles, without nonphysiological permeabilization, has been called
      natural endogenous reverse transcription (NERT). This molecular mechanism has
      been shown to augment HIV-1 infection in initially quiescent peripheral blood
      mononuclear cells (PBMCs) as well as nonproliferating macrophages. As such, this
      process may be important in augmenting the sexual transmission of HIV-1, as
      genital secretions have been shown to stimulate NERT within HIV-1 virion
      particles. Further studies are planned to elucidate fully this initial molecular
      mechanism, which may be critical in understanding the sexual transmission of HIV
      1 and therefore the spread of the AIDS pandemic.

PMID- 9581894
TI  - Infectivity and dynamics of HIV type 1 replication in the blood and reproductive
      tract of HIV type 1-infected women.
AB  - This article delineates several parameters that can influence compartmentalized
      virus shedding in relation to organ-specific factors and cofactors in the blood
      and reproductive tract compartments of women infected with the human
      immunodeficiency virus type 1 (HIV-1). Because a wide variety of techniques is
      currently used for the collection, processing, and quantitation of HIV load in
      the female genital secretions, standard protocols for appropriate sampling and
      testing of these specimens are provided. Studies conducted in our laboratory have
      shown that the levels of cell-free HIV-1 RNA in the female reproductive tract and
      the blood plasma within HIV-1-infected women are different and therefore may
      represent independent events.

PMID- 9581893
TI  - Oral SIV, SHIV, and HIV type 1 infection.
AB  - Several strains of simian immunodeficiency virus (SIV), including uncloned and
      molecularly cloned SIV strains, can cross intact mucosal surfaces after oral
      exposure in both adult and neonatal rhesus macaques, resulting in viremia and
      disease. Cell-free SIV strains as well as infected whole blood have resulted in
      systemic infection after oral inoculation. Neonatal macaques, exposed orally to
      the chimeric SHIV-vpu+, a derivative of SIVmac239 that encodes the env gene of
      the T cell-tropic HIV-IIIB, have also become persistently infected. These data
      indicate that oral exposure to various virus strains, including T cell-tropic
      variants, leads to infection. After nontraumatic inoculation, the oral route was
      more efficient than the rectal route in permitting SIV entry in adult macaques.
      Infection and AIDS resulting from oral exposure of adult macaques have
      implications for the transmission of the human immunodeficiency virus type 1 (HIV
      1) during oral-genital contact.

PMID- 9581895
TI  - Vaginal transmission of SIV: assessing infectivity and hormonal influences in
      macaques inoculated with cell-free and cell-associated viral stocks.
AB  - Cell associated and cell-free simian immunodeficiency virus (SIV) were used to
      investigate transmission of SIV across the vaginal mucosa of rhesus macaques. The
      intact vaginal epithelium was found to be a strong but penetrable barrier to cell
      free SIV infection. We found that 10,000-fold more cell-free SIV was needed to
      infect 100% of the macaques by the vaginal route when compared to the dose needed
      to infect 100% by the intravenous (i.v.) route. Like cell-free SIV, cell
      associated SIV was an efficient means of transmission if given by the i.v. route;
      as few as 2 SIV-infected peripheral blood mononuclear cells (PBMC) were
      infectious inoculum. However, macaques were resistant to cell-associated SIV when
      exposed by the vaginal route; 10,000 SIV-infected PBMC failed to infect vaginally
      inoculated macaques. It was also found that vaginal transmission of cell-free SIV
      to macaques increased during the luteal phase of the menstrual cycle compared to
      the follicular phase. Results with this animal model predict that cell-free human
      immunodeficiency virus (HIV) is likely to be the more efficient mode of HIV
      vaginal transmission and that susceptibility may vary during the menstrual cycle.

PMID- 9581896
TI  - Effects of two progestin-only contraceptives, Depo-Provera and Norplant-II, on
      the vaginal epithelium of rhesus monkeys.
AB  - The objective of this study was to determine whether progestin-only
      contraceptives induce thinning of the vaginal epithelium in nonhuman primates.
      Eight intact rhesus monkeys (four per group) were treated with either a single
      intramuscular injection of 30 mg of Depo-Provera or a subcutaneous insertion of
      Norplant-II (2 x 75 mg rods; day 0). Norplant-II rods were removed 90 days after
      insertion. Vaginal biopsies were obtained during a pretreatment menstrual cycle
      and following treatment on days 10, 30, 60, 118, and 146. Formalin-fixed vaginal
      biopsies were evaluated for epithelial thickness and the degree of
      keratinization. The circulating levels of estradiol, progesterone,
      medroxyprogesterone acetate (MPA), or levonorgestrel (LNG) were monitored
      throughout the study by specific radioimmunoassays. Circulating levels of
      estradiol and progesterone confirmed the stage of the menstrual cycle in which
      pretreatment biopsies were obtained. Following treatment with Depo-Provera, serum
      levels of MPA increased to 2.3 +/- 0.6 ng/ml (x +/- SE, n = 4) within 24 hr.
      Serum levels of MPA were maximal on day 14 (5.5 +/- 0.9 ng/ml), dropped below 1
      ng/ml by day 50, and were nondetectable by day 70. Circulating levels of LNG were
      elevated 24 hr after insertion of Norplant-II (5.8 +/- 3.0 ng/ml), peaked on day
      2 (7.6 +/- 4.2 ng/ml), remained between 1.4 and 6.2 ng/ml from days 14 to 90, and
      were nondetectable by day 118, the first serum sample after removal of Norplant
      II. There were no significant differences (p > 0.05) in the epithelial thickness
      (microm), number of epithelial cell layers, or type of epithelium present in
      vaginal biopsies obtained during the follicular or luteal phases of the
      pretreatment menstrual cycle. Conversely, a pronounced effect of progestin
      treatment was observed on the vaginal epithelium. There were no significant
      differences (p > 0.05) between the two progestin treatment groups, but a
      significant effect (p < 0.05) over time was observed (two-way ANOVA). Compared
      with pretreatment menstrual cycle controls, the vaginal epithelial thickness was
      decreased (p < 0.05) by day 30 or 60 following Norplant-II insertion or Depo
      Provera injection, respectively. The number of epithelial cell layers was also
      decreased (p < 0.05) on days 30 and/or 60 in progestin-treated monkeys compared
      with pretreatment control cycles. Following removal of Norplant-II or metabolic
      excretion of MPA, the vaginal epithellium regenerated and the thickness was no
      longer different (p > 0.05) from the pretreatment control cycle. These data
      demonstrate that progestin-only contraceptives induced thinning of the vaginal
      epithelium in rhesus monkeys, and this effect was rapidly reversible following
      physical or metabolic removal of the progestin.

PMID- 9581897
TI  - Effect of Depo-Provera on the vaginal epithelium and cervical ectopy: report on a
      study in progress.

PMID- 9581898
TI  - Cell-specific targeting with retroviral vectors.

PMID- 9581899
TI  - Suppression of angiogenesis: a means to fight cancer.

PMID- 9581901
TI  - Retroviral vector targeting human cells via c-Kit-stem cell factor interaction.
AB  - Targeted gene transfer into hematopoietic stem cells by retroviral vectors would
      greatly facilitate the development of in vivo strategies for stem cell gene
      therapy. We engineered a recombinant retroviral vector that can target human
      cells expressing a c-Kit receptor via a ligand-receptor interaction. The
      ecotropic (Moloney murine leukemia virus) envelope protein was modified by
      insertion of a sequence encoding the N-terminal 161 amino acids of murine stem
      cell factor (mSCF), the ligand for murine c-Kit. The chimeric envelope protein
      was correctly processed and incorporated into viral particles as efficiently as
      the wild-type envelope protein. Virions pseudotyped with the chimeric envelope
      proteins bound to 293 cells expressing murine c-Kit (293KIT) preferentially;
      however, they could not transduce any c-Kit-positive cells under conventional
      conditions. They could transduce 293KIT cells in the presence of chloroquine, and
      HEL cells expressing human c-Kit on a fibronectin fragment (CH296)-coated dish.
      The fact that recombinant mSCF in the medium at the time of transduction greatly
      reduced the efficiency of both gene deliveries implies that the vector utilized
      the mSCF-c-Kit interaction for the initial step of transduction in either case.
      The vector may prove useful for targeting cells expressing c-Kit on their
      surface.

PMID- 9581900
TI  - Efficient serum-free retroviral gene transfer into primitive human hematopoietic
      progenitor cells by a defined, high-titer, nonconcentrated vector-containing
      medium.
AB  - Defined serum-free conditions have great conceptual advantages for the biological
      safety and standardization of clinical gene transfer into hematopoietic stem
      cells. In the only study reported to date, Sekhar et al. achieved low serum
      conditions by a complex concentration procedure of a retroviral supernatant
      initially containing 10% fetal bovine serum. The high cost, small volume,
      possible coenrichment of serum-derived pathogens, limited recovery of vector
      particles, and low titer of the final diluted medium restrict the clinical
      application of this procedure. Transduction of primitive hematopoietic progenitor
      cells was not demonstrated. In the present study, a defined serum-free medium
      containing high titers of the pseudotyped retroviral vector PG13/LN was generated
      from PG13/LN producer cells without requiring a physical enrichment procedure.
      The transduction of committed hematopoietic progenitor cells in the serum-free
      vector-containing medium was efficient, and similar to that occurring under serum
      containing control conditions. The number of primitive human hematopoietic long
      term culture-initiating cell-derived colonies (LTC-IC-derived colonies) generated
      from CD34+ and CD34+/HLA-DRlo peripheral blood progenitor "stem" cells (PBSCs)
      increased during 7 days of treatment in this vector-containing medium in the
      presence of IL-3, SCF, and flt-3 ligand. The described procedure allowed
      efficient transduction of LTC-IC-derived colonies generated from CD34+, CD34+/HLA
      DRlo, and CD34+/CD38lo PBSCs. This is the first report to demonstrate an increase
      in primitive peripheral blood LTC-IC-derived colonies in vitro as well as their
      efficient transduction in a high-titer, serum-free vector-containing medium that
      can be produced exclusively from defined pharmaceutical-grade components, making
      it ideally suited for applications in clinical gene therapy.

PMID- 9581902
TI  - Retinal functional change caused by adenoviral vector-mediated transfection of
      LacZ gene.
AB  - We examined the effect of insertion of an exogenous gene on retinal function to
      assess the rationale of adenoviral vector-mediated gene transfer for future gene
      therapy. An adenoviral vector expressing bacterial LacZ (AdCALacZ) was injected
      into the eyes of adult rats either intravitreally (group A) or subretinally
      (group B), and the gene expression and retinal function were thus examined at
      different time points after gene transfer for 3 weeks. X-Gal histostaining showed
      that neural retinal cells were transfected in group A and that retinal pigment
      epithelial cells were transfected in group B. The gene transfer was more
      efficient in group B (54.4% of the fixed retinal area was stained) than in group
      A (10.4%). The electroretinogram (ERG) revealed retinal dysfunction in the
      AdCALacZ-transfected rats even at the stage in which the histological damage was
      not apparent by electron microscopy and immunohistochemical studies for
      cytokeratin, S-100 protein, and glial fibrillary acidic protein. The ERG change
      was correlated with the intensity of inflammation, and retinal function recovered
      to the original level by 3 weeks, along with a diminution of inflammation.
      Functional changes were more evident in eyes treated with AdCALacZ than in those
      infected with adenoviral vector with no exogenous gene; however, no histological
      difference was observed between these groups, indicating that the insertion of
      exogenous gene itself affects retinal function. The results showed that different
      kinds of retinal cells could be gene-transferred by an adenoviral vector,
      depending on the application method. The retinal dysfunction caused by each
      adenoviral transfection method was caused by inflammation and the insertion of
      exogenous gene, and this retinal dysfunction was recoverable. In future gene
      therapy, special attention should be given to the method of exogenous gene
      insertion in the retina.

PMID- 9581903
TI  - Differential ganciclovir-mediated cytotoxicity and bystander killing in human
      colon carcinoma cell lines expressing herpes simplex virus thymidine kinase.
AB  - The two human colon carcinoma cell lines HT-29 and SW620, which stably express
      herpes simplex virus thymidine kinase (HSV-TK), are sensitized to the cytotoxic
      effects of the antiviral drug ganciclovir (GCV). Compared with HT-29 cells, SW620
      cells were more sensitive to lower GCV concentrations (<1 microM), accumulated
      GCV triphosphate more rapidly, and incorporated higher levels of GCV into DNA.
      Following a 24-hr exposure to 10 microM GCV, bystander killing was as much as
      sixfold greater in SW620 cells than HT-29 cells. This bystander effect was
      dependent on the level of HSV-TK expression, the number of cells expressing HSV
      TK, and the overall confluency of the cells. However, bystander killing did not
      correlate with gap junctional intercellular communication as determined by
      microinjection of Lucifer Yellow fluorescent dye. SW620 cells were coupled to <3%
      adjacent cells (compared with >50% for HT-29 cells), but were still able to
      transfer phosphorylated GCV to bystander cells as soon as 4 hr after drug was
      added. These results emphasize the importance of cell-specific metabolism in HSV
      TK/GCV-mediated cytotoxicity and may suggest a novel mechanism for bystander
      killing.

PMID- 9581904
TI  - Adenoviral gene transfer in arteries of hypercholesterolemic nonhuman primates.
AB  - Arterial gene transfer with adenoviral vectors is a promising approach for the
      treatment and prevention of vascular disorders. However, in small animals such as
      rats and rabbits adenoviral vectors can have deleterious effects on the artery
      wall. The effects of adenovirus in primate arteries have not been studied. AdRSVn
      LacZ, a replication-defective adenoviral vector, was delivered to the left
      brachial arteries of six hypercholesterolemic cynomolgus monkeys; right brachial
      arteries received vehicle only. Serum was collected before gene transfer and at
      vessel harvest 9 or 10 days later. Recombinant gene expression was present in
      occasional endothelial cells of transduced arteries, and all animals generated
      neutralizing antibodies. In transduced arteries, immunostaining revealed a
      fourfold increase in intimal and medial macrophage accumulation (p < 0.05);
      intimal cellularity was also significantly increased (twofold; p < 0.05). T cell
      density and total cellular proliferation (determined by bromodeoxyuridine
      labeling) were unaffected. In hypercholesterolemic nonhuman primates, adenoviral
      vectors increase vessel wall inflammation and promote the progression of early
      atherosclerotic lesions. The long-term consequences of these observations remain
      unclear; however, a better understanding of host responses to specific vector
      systems appears necessary for the development of safe and effective approaches to
      human vascular gene therapy.

PMID- 9581905
TI  - Regional suppression of tumor growth by in vivo transfer of a cDNA encoding a
      secreted form of the extracellular domain of the flt-1 vascular endothelial
      growth factor receptor.
AB  - Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, is
      overexpressed in most solid tumors. On the basis of the knowledge that solid
      tumor growth beyond a small volume is critically dependent on angiogenesis, and
      that adenovirus (Ad) vectors can mediate efficient in vivo gene transfer and
      expression, we hypothesized that Ad-mediated transfer of a secreted form of the
      extracellular domain of the flt-1 VEGF receptor (Adsflt) would suppress tumor
      growth on a regional basis. To evaluate this concept, three tumor models were
      examined using a murine colon carcinoma cell line and syngeneic BALB/c mice.
      First, mice with preestablished splenic CT26.CL25 tumors and liver metastases
      were given Adsflt on AdNull intravenously and, after 15 days, spleens and livers
      were harvested to quantify tumor burden. Adslft-treated animals had minimal
      residual splenic tumors and liver metastases; in contrast, control animals had
      bulky splenic tumors and extensive liver metastases (p < 0.003). Second, mice
      with preestablished lung metastases showed a significant reduction in pulmonary
      metastases with regionally administered Adslft (intratracheal, p < 0.02) but not
      when the vector was systemically administered (intravenous, p > 0.9). Finally,
      mice with primary subcutaneous tumors treated with intratumoral administration of
      Adslft showed significant tumor suppression (p < 0.05) not observed in AdNull
      treated mice or mice given Adslft intravenously (p > 0.3). We conclude that Ad
      mediated in vivo regional delivery of a secreted form of the extracellular domain
      of the flt-1 VEGF receptor can effectively inhibit regional tumor growth, a
      strategy that may provide a means to control tumor growth within the treated
      organ without the risk of systemic antiangiogenesis.

PMID- 9581906
TI  - Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor
      expression at the site of an allogeneic vaccine.
AB  - Murine tumor models have demonstrated that whole tumor cell vaccines engineered
      to secrete certain cytokines in a paracrine fashion elicit systemic immune
      responses capable of eliminating small amounts of established tumor. In
      particular, autologous tumors that express the cytokine GM-CSF induce potent
      systemic immune responses against poorly immunogenic murine tumors. However,
      phase I clinical trials have demonstrated the technical difficulty of routinely
      expanding primary autologous human tumor cells to the numbers required for
      vaccination, making the generalization of autologous vaccines impractical.
      Dissection of the mechanism by which antitumor immunity is generated has
      demonstrated that GM-CSF recruits professional antigen-presenting cells that act
      as intermediates in presenting tumor antigen to and activating effector T cells.
      Furthermore, the identification of commonly recognized murine and human tumor
      antigens indicates that many are shared rather than unique. These findings would
      suggest that allogeneic as well as autologous tumor cells can be used as the
      vaccinating cells for activating antitumor immunity. A major concern in the
      application of allogeneic vaccines relates to the potential interference of
      allogeneic MHC expression at the vaccine site with priming of tumor-specific T
      cell responses. Here we describe a series of experiments that directly examines
      the effects of allogeneic MHC molecules on the immune-priming capabilities of a
      whole cell tumor vaccine engineered to secrete GM-CSF. The results demonstrate
      that the expression of an allogeneic MHC molecule by a vaccine cell can actually
      enhance the induction of systemic antitumor immunity. In addition, allogeneic MHC
      expression has no inhibitory effect on the ability of GM-CSF-transduced vaccines
      to induce systemic antitumor immunity. These findings support the design of
      clinical trials for testing this more feasible and generalizable allogeneic whole
      tumor cell vaccine approach.

PMID- 9581907
TI  - Suppression of tumorigenicity and metastasis of human renal carcinoma cells by
      infection with retroviral vectors harboring the murine inducible nitric oxide
      synthase gene.
AB  - The purpose of this study was to determine whether retrovirus-mediated transfer
      of the murine macrophage inducible nitric oxide synthase (iNOS) gene can inhibit
      tumorigenicity and metastasis of human renal cancer cells. Retroviral vectors
      encoding murine macrophage iNOS were constructed in the pLXSN retroviral vector
      with the iNOS gene under the control of a long terminal repeat promoter and a
      neomycin resistance gene under the control of an internal simian virus 40
      promoter. Highly metastatic human renal carcinoma SN12PM6 cells were infected
      with control or iNOS retrovirus. Expression of iNOS was confirmed by Northern and
      Western blot analyses, and expression of the functional iNOS protein, i.e.,
      production of nitric oxide (NO), was determined by measuring nitrite accumulation
      in culture supernatants. Noninfected or control cells produced large orthotopic
      tumors in the kidney of nude mice and a larger number of experimental lung
      metastases, whereas iNOS-infected cells produced small tumors in the kidneys and
      few to no lung metastases. The data indicate that the infection of human renal
      cancer cells by retroviruses harboring the murine iNOS gene can induce the
      production of high levels of NO, which is associated with autocytotoxicity,
      suppression of tumorigenicity, and abrogation of metastasis.

PMID- 9581908
TI  - Double suicide gene (cytosine deaminase and herpes simplex virus thymidine
      kinase) but not single gene transfer allows reliable elimination of tumor cells
      in vivo.
AB  - Suicide genes such as cytosine deaminase (CD) and herpes simplex virus thymidine
      kinase (TK) encode products that convert nontoxic substances (prodrugs) into
      toxic metabolites. Suicide gene transfer is currently being used in cancer
      therapy or can be used as a safety modality. To analyze the reliability of
      suicide genes as a safety modality for a vaccination study with viable
      cytokine/B7 gene-modified tumor cells, the individual and combined efficacy of
      the two suicide genes was compared for in vitro and in vivo cell killing of a
      murine mammary adenocarcinoma cell line (TS/A). To adapt the system to an in vivo
      gene delivery situation, bulk cultures cotransfected with the CD and TK gene were
      used instead of selected clones. In vitro, both CD and TK conferred sensitivity
      to the respective prodrug but the combined cytotoxic effects of both gene
      products were always superior. For in vivo analysis BALB/c mice were injected
      subcutaneously with CD- and TK-modified TS/A cells, treated with prodrugs, and
      tumor size was evaluated for a period of 100 days. In the in vivo situation the
      combination of both enzyme/prodrug systems was again most effective. The highest
      single concentration of 5-FC (500 mg/kg) or GCV (100 mg/kg) was not able to fully
      protect the animals from developing tumors, whereas a combination of 5-FC (250
      mg/kg) and GCV (50 mg/kg) resulted in complete tumor eradication. In nude mice
      treated in the same way, most CD/TK tumors could not be eliminated. Furthermore,
      BALB/c mice cured of TS/A-CD/TK tumors developed a systemic tumor immunity
      against challenge with parental TS/A cells. These findings indicate that reliable
      tumor elimination by the suicide genes depends on T cells. The cooperative effect
      of both suicide genes was confirmed in vitro with the human renal cell carcinoma
      line RCC26. We conclude that TK and CD together, but neither gene alone, act as a
      safety mechanism for the elimination of tumor cells in a reliable fashion and
      suggest that a rapid and quantitative antigen release by effective TK- and CD
      mediated tumor destruction is necessary for T cell immunity to develop.

PMID- 9581909
TI  - Adenovirus-mediated gene transfer of the human TIMP-1 gene inhibits smooth muscle
      cell migration and neointimal formation in human saphenous vein.
AB  - Neointimal formation involving smooth muscle cell (SMC) migration and
      proliferation is a common feature of atherosclerosis, restenosis after
      angioplasty, and vein graft intimal thickening. Extracellular matrix remodeling
      by metalloproteinase (MMP) enzymes is an essential component of neointimal
      formation and therefore MMPs are a potential target for localized gene therapy.
      To evaluate this concept using human tissue, we used the highly reproducible
      organ culture model of neointimal formation in human saphenous vein to
      investigate the effect of adenovirus-mediated gene transfer of tissue inhibitor
      of metalloproteinase 1 (TIMP-1) and the bacterial LacZ gene (RAd35) as a control.
      Incubating veins with 100 microl of RAd35 (1.2 x 10(10) pfu/ml) led to expression
      of LacZ in 39 +/- 7% of surface cells but had no effect on SMC proliferation,
      migration, or neointimal formation. Similar infection with RAdTIMP-1 increased
      explanation of TIMP-1 in surface cells and significantly inhibited neointimal
      formation and SMC migration after 14 days by 54% and 78%, respectively (n = 6, p
      < 0.05 Student's paired t test). No effect on SMC proliferation or deleterious
      effect on cell viability was observed. A specific MMP inhibitory effect was
      detected using in situ zymography. These data confirm the importance of MMPs in
      neointimal formation and highlight the potential for application of TIMP gene
      therapy.

PMID- 9581910
TI  - Sustained expression of high levels of human factor IX from human cells implanted
      within an immunoisolation device into athymic rodents.
AB  - Immunoisolation of allogeneic cells within a membrane-bound device is a unique
      approach for gene therapy. We employed an immunoisolation device that protects
      allograft, but not xenograft, cells from destruction, to implant a human
      fibroblast line (MSU 1.2) in athymic rodents. Cells, transduced with the MFG
      human factor IX retroviral vector, and expressing 0.9 microg/10(6) cells/day in
      vitro, were implanted in rats (four 40-microl devices, each containing 2 x 10(7)
      cells, two subcutaneously, two in epididymal fat) and in mice (two 20-microl
      devices, each containing 2 x 10(6) cells, subcutaneously). Plasma factor IX
      levels increased for 50 days, reaching maxima of 203 ng/ml (rat) and 597 ng/ml
      (mouse), and both continued at greater than 100 ng/ml for more than 140 days. A
      clone derived from the transduced cells, making 5 microg of factor IX/10(6)
      cells/day, was implanted within a device (one 20-microl device containing 2.5 x
      10(6) cells), or without a device (1 x 10(7) cells implanted freely), either
      subcutaneously or in epididymal fat. The freely implanted cells expressed
      transiently, reaching more than 100 ng/ml in each site by day 4, but dropped to
      zero by day 20 (subcutaneous) or day 90 (epididymal fat). In devices, levels
      gradually increased to 100 ng/ml (subcutaneous) or 300 ng/ml (epididymal fat),
      remaining high for more than 100 days. These results show long-term, high-level
      expression of a human protein: (1) when cells are implanted within a cell
      transplantation device, but not when the cells are freely implanted, and (2) from
      a transgene driven by a viral promoter. An alloprotective device will enable the
      use of cloned cell lines that can be subjected to stringent quality control
      assessment that is impossible to achieve with autologous approaches.

PMID- 9581911
TI  - A phase I/II study of tgAAV-CF for the treatment of chronic sinusitis in patients
      with cystic fibrosis.

PMID- 9581912
TI  - Comparison of freezing and lyophilizing for preservation of colostrum as a source
      of immunoglobulins for calves.
AB  - Lyophilizing was compared to freezing as a method of colostrum storage. Eight
      lots of colostrum from the first milking were divided into two equal parts; one
      was frozen, and the other was lyophilized. Twenty-two newborn calves were divided
      into two groups and fed either 2 L of frozen and thawed colostrum or 2 L of
      reconstituted lyophilized colostrum. The calves were bled at 12, 18, 24, and 72 h
      after feeding, and levels of the immunoglobulins IgG1, IgG2, IgM, and IgA were
      determined with a radial immunodiffusion assay, in colostrum and sera. The mean
      concentration of individual immunoglobulin isotypes in the sera of calves fed
      either frozen or lyophilized colostrum did not differ significantly. Calves fed
      from the same lots of colostrum had similar immunoglobulin concentrations in
      their sera, irrespective of the method of storage. All immunoglobulin isotypes
      were absorbed with equal efficiency from frozen and lyophilized colostrum as
      determined by calculation of the absorption coefficient.

PMID- 9581913
TI  - Body condition at parturition and postpartum weight gain influence luteal
      activity and concentrations of glucose, insulin, and nonesterified fatty acids in
      plasma of primiparous beef cows.
AB  - Effects of body condition score (BCS) at parturition and postpartum weight gain
      on luteal activity and concentrations of glucose, insulin, and NEFA in plasma
      were evaluated during the breeding season in 242 primiparous beef cows over 3 yr
      (Y) at three locations (L). At approximately 90 d prepartum, cows were blocked by
      breed, expected calving date, and BCS and randomly assigned to diets so that cows
      would calve in BCS of 4, 5, or 6. At calving, cows were blocked by breed, calving
      date, and BCS and randomly allotted to gain .45 (M) or .90 (H) kg/d, from
      parturition to the start of breeding (postpartum nutrition; PPN). During the 60-d
      breeding season, weekly blood samples were obtained from cows, and progesterone,
      insulin, glucose, and NEFA were quantified. Progesterone concentrations greater
      than 1 ng/mL for more than 1 wk indicated luteal activity. To determine the
      possible value of blood constituents as predictors of luteal activity,
      categorical data analyses were performed. Cows with greater BCS at parturition
      had greater concentrations of glucose during breeding (P < .07). Similarly, PPN
      influenced glucose at the beginning of breeding, but the differences were minimal
      after d 28 (PPN x day; P <.001). Cows with greater BCS at parturition and M-PPN
      had greater concentrations of insulin during the breeding season (BCS x PPN; P <
      .02). Cows with a BCS of 6 at parturition had the lowest concentrations of NEFA;
      however, cows on H-PPN had greater concentrations of NEFA (BCS x PPN; P < .03).
      Location, BCS, PPN, and day affected luteal activity (P < .002). Location
      differences in luteal activity were associated with the interval from calving to
      the start of breeding. In general, a greater percentage of cows with BCS of 5 or
      6 at calving had luteal activity by the end of the breeding season.
      Concentrations of metabolites in blood during breeding were not predictive of
      luteal activity. We conclude that BCS at parturition and postpartum nutrition
      influence concentrations of glucose, insulin, and NEFA in blood and the onset of
      luteal activity in primiparous beef cows.

PMID- 9581914
TI  - Genetics of the interval from weaning to estrus in first-litter sows: correlated
      responses.
AB  - The objective of this study was to evaluate relationships between rebreeding
      performance and growth performance (n = 3,777 gilts) and rebreeding performance
      and reproductive performance (n = 2,242 sows). Our data were from a selection
      experiment for shorter intervals from weaning to estrus after the first parity
      (IWE), involving Dutch Landrace pigs, in which a selection line and a control
      line without selection were maintained for eight generations. Relationships were
      evaluated before and after transforming IWE to normal interval (NI; IWE < or = 7
      d), prolonged interval (PI; IWE > 7 d), and incidence of a prolonged interval
      (INC). Heritabilities of NI, PI, and INC were .18, .17, and .27. Within-line
      phenotypic and genetic trends in growth and reproductive performance were not
      different from zero and did not diverge as a correlated response to the selection
      applied. Phenotypic correlations between IWE, NI, or PI and growth or
      reproductive performance were low and ranged from -.14 to .11. Genetic
      correlations were higher, and, for the majority of traits, the genetic
      correlations with NI and PI had a different sign. Phenotypic and genetic
      contrasts between sows with NI and sows with PI different from zero indicated
      that INC may increase as a correlated response to selection for reproductive
      performance. Analyses using untransformed IWE or data from populations selected
      for rebreeding performance may underestimate the correlated response in IWE due
      to selection on economically important traits.

PMID- 9581915
TI  - The role of animal science in natural resource management: current decision
      making models and future needs.
AB  - Sustainable systems for land and natural resource management must be
      biologically, economically, and socially sustainable. Scientists and educators
      have historically viewed their role as developing new knowledge and technology to
      enhance biological and economic sustainability. Scientists have traditionally
      viewed sociopolitical sustainability and policy development as beyond our
      appropriate roles. Changing public values and perceptions on appropriate land use
      and natural resource protection are forcing land grant universities and their
      scientists and educators to re-evaluate traditional paradigms. The animal science
      community, in concert with the social and other biological sciences, must become
      more proactive in decision making processes on appropriate land use and natural
      resource management if we are to remain relevant. This paper describes the
      current situation and outlines approaches for the research and education
      communities to be important contributors to collaborative decision making
      processes on land and natural resource management.

PMID- 9581916
TI  - Sheep fed grain prefer foods and solutions that attenuate acidosis.
AB  - We conducted experiments to determine whether lambs fed grain prefer foods and
      solutions containing sodium bicarbonate (NaHCO3) and lasalocid, compounds capable
      of attenuating acidosis. In Exp. 1, we determined whether lambs fed barley
      preferred flavored rabbit pellets (RP) containing NaHCO3 and lasalocid. Lambs in
      two groups (n = 10/group) were fed increasing amounts of barley on d 1 to 12 (300
      to 1,100 g) and again on d 23 to 34 (300 to 1,350 g). After ingesting barley on d
      1 to 12, lambs were fed ground RP containing lasalocid and NaHCO3 (i.e.,
      medicated) and flavored with either 2% onion (group 1) or 2% oregano (group 2).
      During d 23 to 34, lambs were fed unmedicated RP containing NaCl and flavored
      with either 2% oregano (group 1) or 2% onion (group 2). During preference tests
      on d 35 to 40, lambs fed grain preferred RP with NaHCO3 to RP with NaCl (151 vs.
      96 g; P < .01). In the Exp. 2, we determined whether wheat ingestion affected
      consumption of aqueous solutions containing NaHCO3. In trial 1, 28 lambs were
      assigned to four treatments: 1) low-wheat + 2% NaHCO3, 2) high-wheat + 2% NaHCO3,
      3) low-wheat + water, and 4) high-wheat + water. For 12 d from 0800 to 0830,
      lambs in treatments 1 and 3 were fed 300 g of wheat and lambs in treatments 2 and
      4 were fed up to 1,300 g of wheat; fluids (NaHCO3 and water) were then offered
      from 0930 to 1230 daily. Lambs drank more NaHCO3 on the high- than on the low
      wheat diet (1,332 vs 890 g; P = .03); water consumption was similar for lambs on
      the high- and low-wheat diets (1,675 vs 1,700 g; P > .10). In trial 2, lambs in
      treatments 3 and 4 were offered a solution containing 1.4% NaCl. For 13 d from
      0800 to 0830, lambs in treatments 1 and 3 were fed 500 g of wheat and lambs in
      treatments 2 and 4 were fed up to 1,700 g of wheat. Lambs had access to fluids
      from 0800 to 1200 daily. Lambs drank nearly twice as much NaHCO3 solution on the
      high- than on the low-wheat diet (1,066 vs 572 g), whereas they drank only 1.4
      times more NaCl solution on the high- than on the low-wheat diet (888 vs. 634 g;
      P < .001). Fewer lambs showed signs of acidosis in treatment 2 than in treatment
      4 in trials 1 (2 vs 9) and 2 (7 vs 17). Collectively, these results are
      consistent with the hypothesis that lambs fed grain prefer substances that
      attenuate acidosis.

PMID- 9581917
TI  - Manipulating odor cues facilitates add-on fostering in sheep.
AB  - Manipulating the odor of a ewe's own and alien lambs has been used to facilitate
      fostering a second lamb on ewes with a single offspring (add-on fostering).
      Previous research has demonstrated that familiar odor cues must be present on the
      own and alien young to achieve successful and rapid adoptions. Familiar odors may
      consist of natural own-lamb odors or artificial odors previously applied to the
      lambs involved. In the present study (Exp. 1), an artificial odorant (neatsfoot
      oil) was applied to the own and alien lambs shortly after birth to establish a
      common familiar odor. Acceptance tests were conducted daily over a 72 h period.
      In Exp. 2, neatsfoot oil was again used as a common artificial odorant to
      facilitate add-on fostering, but, in addition, the natural odors of own and alien
      lambs were transposed by exchanging cloth stockinette jackets worn by the lambs.
      In Exp. 1, 9 of 18 ewes (50%) met the criteria for accepting their own and alien
      lambs within 72 h. Seven of these nine ewes (78%) accepted the alien lamb
      immediately. In Exp. 2, 24 of 30 ewes (80%) accepted their own and alien young,
      and 20 of the 24 acceptances (83%) were immediate. We conclude that add-on
      fostering may be limited only by our inability to properly match familiar-odor
      cues on own and alien lambs.

PMID- 9581918
TI  - How readily will sheep walk for a preferred forage?
AB  - We studied how ewes chose between a poor-quality hay freely available and a good
      quality one offered in limited quantities when they walked across an indoor test
      area. To determine what dictates a ewe's behavior, we varied the accessibility of
      the good hay by changing the quantity that rewarded the walk (2, 4, 8, 16, or 32
      g) and the distance walked (23 or 46 m). Ewes were more reluctant to walk for the
      good hay as reward level decreased. For a given reward, average preference for
      good hay (P(GH)) also fell when ewes had to walk 46 m to be rewarded. In each
      comparison, for the same reward to distance (Rew/Dist) ratio, average P(GH) did
      not differ. We determined the correlation between P(GH) and Rew/Dist using data
      from three experiments with ewes offered a similar choice. The best model
      accounted for 85% of the corrected total sum of squares. Good hay procurement
      cost thus dictated a ewe's behavior. Choice was suboptimal only, either due to
      the test conditions, discrimination errors, or an animal's will to select a mixed
      diet. Our results suggest that, within its perceptive field, a ewe will equally
      walk to resources that have the same edible biomass relative to the distance to
      the patch.

PMID- 9581919
TI  - Comparison of image analysis, exertion force, and behavior measurements for use
      in the assessment of beef cattle responses to hot-iron and freeze branding.
AB  - Thirty-three steers (328 +/- 2 kg) from a total of 300 animals were randomly
      selected for a comparison of techniques designed to quantify the behavioral
      response to painful procedures. The steers were randomly assigned to freeze
      branding, (F), hot-iron branding (H), and sham branding (S) treatments. The
      responses of all steers were videotaped to quantify the amount and intensity of
      head movements during branding. In addition, the force that steers exerted on the
      headgate and squeeze chute during branding was recorded using strain gauges and
      load cells. Behaviors believed to be indicative of pain (tail-flicking, kicking,
      falling, and vocalizing) were also recorded during branding. These techniques
      were compared for their effectiveness in measuring behavioral responses of steers
      during branding. Hot-iron-branded steers had greater maximum and average head
      movement distances and velocities than F or S steers (P < .05), and F steers only
      had greater maximum values than S animals (P < .05). The maximum exertion forces
      obtained from headgate load cells were also greater in H than in F or S steers (P
      < .05); however, no differences were observed between H and F treatments for
      squeeze load cell or headgate strain gauge data. Hot-iron-branded steers had the
      greatest incidence of tail-flicks, kicks, falls in the chute, and vocalizations,
      and S steers had the least. Results indicate that H steers experienced more
      discomfort at the time of branding than F and S steers, whereas F steers
      experienced more discomfort than shams. Image analysis was a superior technique
      for detecting treatment differences compared with exertion force measurements and
      frequency counts of tail-flicks, kicks, falls, and vocalization during branding.

PMID- 9581920
TI  - A computer model to predict composition of empty body weight changes in cattle at
      all stages of maturity.
AB  - We developed methods to integrate two published models that partitioned gains in
      empty body weight (EBW) to fat and fat-free matter. These models were based on
      separate mathematical formulations for growing and mature cattle. We assumed that
      as cattle grow from birth to maturity a transition would occur at some point in
      the life cycle from the growing to the mature mathematical formulation. This
      transition point and the rate at which the transition occurs between the two
      mechanisms were estimated from published data. Evaluation results with data on
      steers that were full-fed to grow from birth to 815 kg EBW showed that the
      methods used to integrate the two models provided an accurate prediction of empty
      body composition at final slaughter. Evaluation results with full-fed growing
      cattle that were slaughtered at market weights suggest that partitioning of EBW
      gains can be fully described by the mathematical formulation used for growing
      cattle. However, for cattle that were restricted in growth, then realimented, the
      results showed that a model with a transition to the mathematical formulation for
      mature cattle, during the realimentation phase, accurately predicted the observed
      final composition. These results suggest that the integrated model would
      accurately predict the changes in body composition of cattle of all ages, under
      different systems of nutritional management.

PMID- 9581921
TI  - The beta-agonist cimaterol directly enhances chronic protein accretion in
      skeletal muscle.
AB  - Our objective was to determine whether the chronic anabolic effects of beta
      adrenergic agonists on skeletal muscle are direct and how long they are
      maintained. We studied acute (6 h) and chronic (1 to 20 d) effects of cimaterol
      (CIM) on skeletal muscle metabolism and protein accretion by use of close
      arterial infusion in the hindlimbs of six young steers. Surgical catheterizations
      were conducted to allow continuous infusion of CIM (.5 microg/min) or saline into
      the external iliac artery of contralateral hindlimbs and simultaneous sampling
      for arteriovenous difference measurements. Hindlimb blood flow and net flux of
      amino acids, glucose, lactate, and NEFA were determined during a basal period
      before infusion, at 6 h, and at 1, 3, 7, 14, and 20 d of infusion. Cimaterol
      infusion acutely stimulated blood flow and caused acute mobilization of nitrogen
      (alanine), NEFA, and lactate from the treated hindlimb. Cimaterol infusion
      increased net uptake of amino acids (P < .05) in treated and control hindlimbs
      after 1 d of CIM infusion, but a progressive increase between 1 and 14 d of
      infusion was observed only in the treated hindlimbs. Net uptake of total amino
      acids in the treated hindlimb was increased 50 and 80% (P < .05) at 7 and 14 d,
      respectively, when compared to the control hindlimb and was increased 260% at d
      14 when compared with the basal period. Net amino acid uptake was not different
      between treated and control hindlimbs by d 20 of CIM infusion. Integration of net
      tyrosine and phenylalanine uptake over the entire infusion period predicted a 10%
      difference in skeletal muscle protein mass between treated and control hindlimbs.
      Semitendinosus and semimembranosus muscles in the treated hindlimb contained 9
      and 11% greater protein content, respectively (P < .05), at the end of the
      infusion period. Results provide a quantitative description of the temporal
      pattern of transient effects of CIM on skeletal muscle metabolism and protein
      accretion and provide evidence that these are direct effects.

PMID- 9581922
TI  - Effect of corticosterone on beta-adrenoceptor density in rat skeletal muscle.
AB  - Corticosteroid hormones increase the density of beta-adrenoceptors in some
      tissues and may be able to prevent the anabolic effects of beta-agonists from
      becoming attenuated. The aim of this study was to find a suitable dose of
      corticosterone that would up-regulate beta2-adrenoceptors in skeletal muscle
      without arresting the animal's growth. Male rats were given five daily injections
      of corticosterone at 0, 6.25, 12.5, 25, or 50 mg/kg. The animals were far more
      sensitive to the catabolic effects of this steroid than female rats used in a
      previous study. There was no change in food intake, liver, heart, or soleus
      muscle mass, but corticosterone caused a dose-related decrease in weight gain,
      carcass weight, omental fat pad weight, and gastrocnemius/plantaris muscle mass
      (P < .01). From a regression of muscle mass against dose, we calculated that 4.4
      mg x kg(-1) x d(-1) would be the largest dose of corticosterone that a male rat
      could tolerate without any catabolic effect in skeletal muscle. Corticosterone
      failed to increase beta-adrenoceptor density at any of the doses tested. We
      conclude that corticosterone treatment is unlikely to be effective at enhancing
      the growth response of male rats to beta-agonists.

PMID- 9581923
TI  - Developmental expression and location of IGF-I and IGF-II mRNA and protein in
      skeletal muscle.
AB  - To investigate the role of IGF in muscle development in vivo, developmental
      expression and location of IGF-I and -II protein and mRNA were examined in fetal,
      postnatal, and adult skeletal muscle. Muscle tissue was collected from 30-, 44-,
      59-, 68-, 75-, 89-, and 109-d porcine fetuses, 21-d neonatal pigs, and 6-mo-old
      (adult) pigs. Relative amounts of IGF-II mRNA peaked (P < .05) in 59-d fetal
      muscle and decreased thereafter. Inversely, muscle IGF-I expression increased (P
      < .05) to maximal levels around birth. For in situ hybridization, frozen muscle
      tissue sections (10 microm) were hybridized with a hydrolyzed form of the same
      riboprobes or incubated with polyclonal or monoclonal antibodies to IGF-I or -II,
      respectively. The majority of IGF-I and IGF-II mRNA was localized to developing
      muscle fibers, whereas little signal was found in the surrounding connective
      tissues. Immunofluorescent localization of IGF-I and -II confirmed that muscle
      IGF are present in developing muscle fibers. Collectively, these data show that
      IGF-I and -II are expressed and produced primarily in muscle cells within
      developing muscle tissue and support the hypothesis that IGF-I and -II modulate
      fetal muscle development.

PMID- 9581924
TI  - Effect of clenbuterol on endocrine status and nitrogen and energy balance in food
      restricted rats.
AB  - We administered clenbuterol as a dietary admixture (4 mg/kg diet) to three groups
      of male Wistar rats (n = 8) housed individually in metabolism cages and fed for
      15 d at 110, 160, and 235% (ad libitum) of the estimated requirement for energy
      maintenance. Untreated groups at each level of energy intake and a baseline group
      were also included. In the diet-restricted rats, clenbuterol induced greater and
      more persistent increases in nitrogen balance, biological value, and net protein
      utilization than it did in the ad libitum-fed rats. Energy balance was increased
      by clenbuterol treatment in the diet-restricted rats, with no significant changes
      occurring in the ad libitum fed rats. Compared with untreated rats, clenbuterol
      reduced blood glucose in all diet groups and serum insulin in the ad libitum and
      the moderately restricted (160%) rats. Serum IGF-I was increased in the highly
      restricted (110%) rats. Corticosterone levels were increased by clenbuterol
      treatment in all diet groups. These results are consistent with previous results
      showing that clenbuterol can help improve growth, but they also show that
      clenbuterol can offset the effects of food restriction on protein and energy
      metabolism.

PMID- 9581925
TI  - Beef color update: the role for vitamin E.
AB  - Dietary supplementation of livestock with vitamin E results in improved quality
      of meat subsequently obtained from these animals. The effect is especially
      noteworthy in cattle, in which the primary effects are delayed discoloration and
      lipid oxidation. A threshold level of alpha-tocopherol in muscle ensures a
      detectable effect; dietary strategies for attaining this threshold must consider
      tocopherol status of cattle arriving at the feedyard and duration and level of
      supplementation. The alpha-tocopherol concentration in muscle must be determined
      before proper interpretation of experimental results can be made. Muscles vary in
      their color stability, and this relative difference is not changed by vitamin E
      supplementation. Several in vitro models have been used to characterize the
      interaction between alpha-tocopherol, lipid oxidation, and oxymyoglobin
      oxidation. Alpha-tocopherol seems to exert its color-stabilizing effect by
      indirectly delaying oxymyoglobin oxidation via direct inhibition of lipid
      oxidation. However, recent results demonstrating a protective effect of alpha
      tocopherol toward oxymyoglobin in low-oxygen atmospheres indicate that additional
      mechanisms may exist. A better understanding of the fundamental bases for
      protection of water-soluble myoglobin by lipid-soluble alpha-tocopherol is needed
      to optimize this beneficial effect.

PMID- 9581926
TI  - Beef customer satisfaction: role of cut, USDA quality grade, and city on in-home
      consumer ratings.
AB  - An in-home beef study evaluated consumer ratings from moderate-to-heavy beef
      users as influenced by cut (top loin, top sirloin, and top round steaks), USDA
      quality grade (Top Choice, Low Choice, High Select, and Low Select), and city
      (Chicago, Houston, Philadelphia, and San Francisco). Consumers (n = 2,212)
      evaluated each steak for overall like (OLIKE), tenderness (TEND), juiciness
      (JUIC), flavor desirability (DFLAV), and flavor intensity (IFLAV) using 23-point
      hedonic scales (23 = like extremely, extremely tender, extremely juicy, like
      extremely, and an extreme amount of flavor; 1 = dislike extremely, not at all
      tender, not at all juicy, dislike extremely, and no flavor at all). A USDA grade
      x cut interaction existed for OLIKE (P < .05). Consumers rated top loin steaks
      highest (P < .05) in OLIKE and ranked Top Choice highest of all steaks (P < .05).
      Within the top loin, consumers were not (P > .05) able to distinguish OLIKE
      differences between Low Choice and High Select or between High Select and Low
      Select. For OLIKE, top sirloin was rated intermediate (P < .05) of the three
      cuts, and consumers were not able to detect (P > .05) USDA quality grade
      differences. For OLIKE, top round was the lowest-rated (P < .05) cut. However,
      consumers preferred (OLIKE, P < .05) Top Choice to the other USDA grades offered.
      Grade and city interacted to affect TEND, JUIC, DFLAV, and IFLAV. The cut x city
      interaction was significant for all palatability attributes. Cut and city
      affected customer satisfaction more than USDA quality grade. Tenderness and
      flavor were important and equal contributors to OLIKE, r = .85 and r = .86,
      respectively.

PMID- 9581927
TI  - Effect of postmortem storage on the Z-line region of titin in bovine muscle.
AB  - Myofibrils were prepared from bovine muscles (cutaneous trunci, rectus abdominis,
      psoas major, and masseter) and compared between different aging periods at 4
      degrees C (0, 1, 2, 4, 8, and 16 d). Myofibrils were stained with an antibody
      directed against a 56-kDa fragment (FE-RE) of titin located in the Z-line region.
      Unaged myofibrils from all four muscles showed a single stained band at the Z
      line with similar intensities. Postmortem time did not significantly affect the
      total amount of fluorescence in the sarcomere, suggesting the titin FE-RE epitope
      was not degraded nor were titin fragments containing this epitope released during
      storage. However, the fluorescence patterns were altered. The relative
      fluorescence intensity at the Z-line decreased but that in the I-band increased
      gradually, showing the translocation of some titin FE-RE epitopes during the
      aging period. This suggested that a cleavage occurred in a region of titin very
      close to the Z-line during postmortem storage. Usually the position of maximum
      fluorescence remained at the Z-line, although about 1/3 of the myofibrils from
      rectus abdominis showed a two-band pattern around the Z-line after 16 d of aging.
      The titin changes observed may be related to the increased fragility of the
      myofibril and the improvement of meat tenderness during postmortem storage.

PMID- 9581928
TI  - Backfat fatty acid evolution in swine fed diets high in either cis
      monounsaturated, trans, or (n-3) fats.
AB  - To evaluate the effects of dietary fats on the evolution of the fatty acid
      profile of swine backfat, 30 castrated Landrace x Duroc pigs averaging 26 kg were
      assigned three diets with 4% added pomace oil (O), hydrogenated fat (H), or
      linseed oil (L). Subcutaneous fat samples were taken from biopsies at 0, 17, 31,
      and 60 d, and at 24 h postmortem when pigs averaged 95 kg live weight at 82 d on
      trial. On d 17, saturated fatty acid (SFA) content was 2% lower for the O diet
      than for H and L (P < .089). There was a linear increase in SFA at a monthly rate
      of 2% in the three diets. The increase was mainly due to 18:0; palmitic acid
      percentages showed no variation. Pigs fed the O diet experienced exponential
      increases in monounsaturated fatty acids (MUFA), especially until d 17 (P <
      .001). In pigs fed the H or L diets, MUFA contents decreased at a monthly rate of
      2.40%, and the same happened with oleic acid contents. Diets rich in (n-3) (L)
      and trans-fatty acids (H) caused exponential increases in swine backfat contents
      of total (n-3) and total trans, respectively. At d 31 (P < .001), 72 to 73% of
      the maximum contents had been reached. Contents for 20:3(n-3), 20:5(n-3), and
      22:5(n-3) follow a pattern similar to that of their precursor 18:3(n-3), showing
      an exponential increase in pigs fed the L diet, and contents for H and O
      treatments were lower (P < .001). The three diets caused a linear decrease in (n
      6) fatty acid contents throughout the 82-d trial.

PMID- 9581929
TI  - The effect of narasin on apparent nitrogen digestibility and large intestine
      volatile fatty acid concentrations in finishing swine.
AB  - The effect of narasin on apparent nitrogen and dry matter digestibilities and
      large intestine VFA concentrations in finishing swine was investigated. The study
      used 21 crossbred barrows averaging 72 kg. Seven blocks were formed on the basis
      of pretreatment dry matter digestibility, and barrows were randomly assigned to
      three treatments in each block. Treatments consisted of a control (C) and narasin
      (N15 and N30) applied at 15 and 30 ppm, respectively. Fecal and urine samples
      were collected. Upon the completion of the digestibility work, intestinal samples
      were taken from three locations, and VFA concentrations for each animal were
      measured. Weight gains for the N15 and N30 treatments were increased 3.0 and 6.0%
      (not significant), respectively, over control. Fecal nitrogen was decreased (P <
      .05) in the narasin-fed barrows, and apparent nitrogen digestibility was
      increased (P < .05). Neither nitrogen retention nor urinary nitrogen excretion
      was altered (P > .05) due to narasin. There were no increases (P > .05) in
      apparent dry matter digestibility due to narasin. Analysis of pooled colon
      samples showed an increase (P < .05) in the concentration of propionic acid in
      relation to acetic and butyric in the narasin-fed barrows. Butyric acid was
      reduced (P < .05) in the transverse colon of narasin-fed barrows. In summary,
      narasin administration to finishing barrows resulted in improved apparent
      nitrogen digestibility, thus decreasing fecal nitrogen, and increased relative
      concentrations of propionic acid in the large intestine.

PMID- 9581930
TI  - Influence of dietary lysine on the utilization of zinc from zinc sulfate and a
      zinc-lysine complex by young pigs.
AB  - We conducted two trials (n = 144 and 96) to evaluate the response of feeding
      either ZnSO4 x H2O or a zinc-lysine complex (ZnLys) in combination with various
      lysine levels on growth performance, liver, kidney, and 10th rib Zn
      concentration, serum Zn humoral immune response and absorption of Zn (chromic
      oxide method) of young pigs. The following treatments were started after a 7-d
      postweaning adjustment during which all pigs were fed a common diet adequate in
      zinc. Diets were as follows: 1) basal 1 (B1), .8% dietary lysine without added Zn
      (basal contained 32 ppm Zn); 2) B1 plus 100 ppm Zn from ZnSO4; 3) B1 plus 100 ppm
      Zn from ZnLys, 4) basal 2 (B2), 1.1% lysine without added Zn; 5) B2 plus 100 ppm
      Zn from ZnSO4; 6) B2 plus 100 ppm Zn from ZnLys. In Trial 1 only, 100 ppm Zn from
      ZnSO4 (diet 7) or ZnLys (diet 8) was added to a .95% lysine basal diet. The basal
      20% CP diet contained 9.0% corn gluten meal to lower the total lysine level.
      Within lysine level, all diets were made isolysinic by using crystalline lysine.
      Zinc sulfate, ZnLys, or lysine replaced dextrose in the basal diet. After 4 wk on
      test, one barrow in each pen was killed; liver, kidney, left 10th rib, and
      contents of the stomach, small intestine, and lower colon were removed for Zn
      analyses. Performance (ADG and ADFI) was only improved (P < .05) in one of the
      two trials when either zinc source was added to the basal diets, but performance
      was higher (P < .01) for pigs fed 1.1% lysine diets compared with .8% lysine
      diets in both trials. Serum Zn concentrations were lower (P < .001) for pigs fed
      both dietary lysine basal diets without added Zn. The humoral response to sheep
      red blood cells and ovalbumin was not influenced (P > .20) by lysine level, or Zn
      level and source. Pigs fed diets without added Zn had lower (P < .001) liver,
      kidney, and rib Zn concentrations than pigs fed diets with added Zn regardless of
      Zn source. Dietary lysine did not influence liver Zn, but kidney (P < .01) and
      rib (P < .001) Zn concentrations were lower for pigs fed the higher lysine level.
      Digestibility coefficients of Zn were lower in the stomach for pigs fed diets
      without added Zn, similar among Zn levels and sources in the small intestine, and
      higher in the lower colon for pigs fed the basal diets without added Zn. Lysine
      level and Zn source did not influence Zn absorption. The ZnSO4 and a zinc lysine
      complex seemed to be equally effective in promoting growth performance, zinc
      absorption, and tissue stores of young pigs when diets contained deficient,
      adequate, or slightly more than adequate levels of lysine.

PMID- 9581931
TI  - Influence of dietary lysine on growth performance and carcass characteristics of
      late-finishing gilts.
AB  - We conducted two experiments evaluating the lysine requirement of 91- to 113-kg
      gilts. Gilts (PIC L326 x C-22) with initial body weights of 42 (Exp. 1) or 39 kg
      (Exp. 2) were blocked by weight in a randomized complete block design. Experiment
      1 included 105 gilts, with seven gilts per pen and five replications (pens) per
      treatment. Experiment 2 included 125 gilts, with eight gilts per pen and four
      replications (pens) per treatment. Gilts were fed a corn-soybean meal diet (no
      crystalline lysine) containing 1.0% total lysine from 39 to 68 kg and .80% total
      lysine from 68 to 91 kg. In Exp. 1, when the average weight of gilts within a
      block reached 91 kg, gilts were fed corn-soybean meal diets containing .40, .55,
      or .70% total lysine. Increasing dietary lysine increased (linear, P < .05) ADG,
      daily lysine intake (11.3, 15.1, and 19.8 g/d), gain/feed, plasma urea N, and
      carcass lean percentage but decreased 10th rib fat depth. Because of the linear
      responses in Exp. 1, Exp. 2 was conducted with corn-soybean meal diets containing
      .60, .70, .80, or .90% total lysine. Increasing total dietary lysine had no
      effect on ADG, gain/feed, 10th rib fat depth, or carcass lean percentage (P >
      .10). Daily lysine intake increased (linear, P < .01) with increasing dietary
      lysine (18.1, 21.1, 23.9, 26.5 g/d). Based on these results, the total dietary
      lysine requirement for 91- to 113-kg gilts is approximately .60% total lysine,
      which corresponds to approximately 18 g/d lysine intake.

PMID- 9581932
TI  - Ratio of total sulfur amino acids to lysine for finishing pigs.
AB  - We conducted two experiments to determine the optimum ratio of total sulfur amino
      acids (TSAA) to Lys for late finishing pigs. In Exp. 1, 50 barrows and 50 gilts
      were allotted to treatments with three replicates of three or four pigs per
      replicate in a randomized complete block (RCB) design within a split-plot
      arrangement of treatments. Sex was the whole plot and TSAA:Lys ratio was the
      subplot. Average initial and final BW were 77 and 111 kg. Barrows and gilts were
      fed diets formulated to contain .55 and .65% Lys, respectively. The ratios of
      TSAA:Lys were .50, .55, .60, .65, and .70. Diets met or exceeded an ideal amino
      acid pattern for all indispensable amino acids (except TSAA), and all diets were
      isonitrogenous and equal in electrolyte balance. In Exp. 2, 60 gilts were
      allotted to five treatments with four replicates of three gilts each in a RCB
      design. Average initial and final BW were 74 and 110 kg. Gilts were fed diets
      formulated to contain .65% Lys. The ratios of TSAA:Lys were .35, .425, .50, .575,
      and .65. In Exp. 1, there were no TSAA:Lys ratio effects (P > .10) for ADG, final
      BW, percentage muscle, longissimus muscle area, carcass length, percentage fat
      free lean (PFFLEAN), lean gain per day (LGD), total fat (TOFAT), percentage TOFAT
      (PTOFAT), fat gain per day (FGD), lean:fat, retained energy in TOFAT as ether
      extractable lipid (RE-F), retained energy (RE), or serum urea N (SUN). Feed
      intake (ADFI) was greater (quadratic, P < .05) for pigs fed .70 TSAA:Lys than for
      pigs fed any other treatment. Hot carcass weight, psoas muscle weight, 10th rib
      fat thickness, dressing percentage, fat-free lean (FFLEAN), and retained energy
      in FFLEAN as protein (RE-P) responded inconsistently to TSAA:Lys ratio, resulting
      in cubic (P < .09) effects. In Exp. 2, ADFI (linear, P < .08), TOFAT (linear, P <
      .05), PTOFAT (linear, P < .07), FGD (linear, P < .05), RE-F (linear, P < .05), RE
      (linear, P < .05), and SUN (linear, P < .02; quadratic, P < .01) decreased as
      TSAA:Lys ratio increased. Also, gain:feed (GF) (linear, P < .01; quadratic, P <
      .04), PFFLEAN (linear, P < .04), and lean:fat (linear, P < .04) increased as
      TSAA:Lys ratio increased. One-slope, broken-line regression models estimated
      required ratios of TSAA:Lys of .44 (SUN), .40 (ADG), .47 (ADFI), .45 (GF), .45
      (FFLEAN), .44 (LGD), .65 (TOFAT), .65 (FGD), .44 (RE-P), .65 (RE-F), .65 (RE),
      and .57 (lean:fat). Thus, for growth and muscling traits of late finishing pigs,
      the optimum ratio of TSAA:Lys is less than the current proposed ratio (.65), but
      to minimize fat accretion, the ratio is .65.

PMID- 9581933
TI  - The lysine requirement of lactating primiparous sows.
AB  - We conducted an experiment with 289 primiparous sows to evaluate the effect of
      lysine intake on lactation and subsequent reproductive performance. Sows were
      randomly allotted to one of five experimental corn-soybean meal lactation diets.
      The first four diets contained incremental levels of apparently digestible lysine
      (.67, .86, 1.06, and 1.25%) and provided digestible lysine intakes of 27, 34, 41,
      and 48 g/d. All lysine was derived from intact protein sources. Synthetic valine,
      threonine, and methionine were used to maintain ratios to lysine that were equal
      to those of the .67% lysine diet. The fifth diet contained 1.06% digestible
      lysine and provided 43 g/d digestible lysine, but no additional synthetic amino
      acids were added. The average lactation length in this study was 16.9 +/- .2 d.
      Lysine intake during lactation did not affect number of pigs weaned, litter
      growth rate, sow backfat loss, or weaning to mating interval. Sow weight loss and
      loin eye area loss decreased quadratically (P < .05) with increasing lysine
      intake. These were minimized at 45 and 48 g/d digestible lysine, respectively.
      Removing synthetic amino acids from the 1.06% digestible lysine diet resulted in
      an increased litter growth rate (1.98 vs 2.15 kg/d, P < .05). Increasing dietary
      lysine intake while maintaining amino acid ratios to lysine for valine,
      threonine, and total sulfur amino acids during the first lactation resulted in a
      linear (P < .05) decrease in second litter total born. However, removal of
      synthetic amino acids from the 1.06% digestible lysine diet resulted in an
      increased second litter total born (12.9 vs 11.2, P < .05), which tended to be
      higher compared with the .67% digestible lysine treatment (12.9 vs 11.7, P =
      .13). The results suggest that primiparous sows are able to mobilize sufficient
      body reserves to maintain a high level of milk production at low levels of lysine
      intake during a 17-d lactation. Higher levels (45 to 48 g/d) of digestible lysine
      are required to minimize body protein loss. The source or composition of amino
      acids in the lactation diet may have an effect on second litter size.

PMID- 9581934
TI  - Effect of lean growth genotype and dietary amino acid regimen on the lactational
      performance of sows.
AB  - The effect of dietary amino acid regimen and genetic capacity for lean tissue
      growth on the lactational performance of sows was determined in primiparous sows
      with a high (350 to 390 g/d) or low (240 to 280 g/d) genetic capacity for lean
      tissue growth from 18 to 110 kg of body weight. During lactation, sows were
      offered daily 6.5 kg of one of four fortified corn-soybean meal diets containing
      .58, .77, .96, and 1.15% lysine (L). Litters were standardized to 14 pigs within
      8 h after birth. On d 2 of lactation, the high lean growth (LG) sows possessed
      more proteinaceous tissues and protein and less fat tissue and lipid. During
      lactation (d 2 to 28 postpartum), high LG sows consumed more feed, mobilized more
      body protein, and lost less body lipid. Milk, milk energy, and milk lysine yields
      (pooled across dietary regimens) were similar between genotypes. As daily dietary
      lysine intakes increased from 27 to 62 g and total digestible lysine supplies
      (from diet and mobilized tissues) increased from 39 to 68 g, daily yields of
      milk, milk energy, and milk lysine increased, but the magnitude of the response
      differed (P < .05) between genotypes, evidently because of differences in the
      ability of the high and low LG sows to mobilize energy from body tissue. Based on
      these data, the lactational capacities of high and low LG sows nursing 12 to 14
      pigs are similar when similar supplies of lysine and energy are available from
      dietary intake and mobilized body tissue stores. When supplies of ME do not limit
      milk synthesis, daily digestible lysine intakes of at least 54 g (> or = 66 g
      from a corn-soy diet) are needed by these sows nursing litters of 12 to 14 pigs
      to support milk synthesis and minimize maternal protein losses. This is
      equivalent to a total digestible lysine need of 4.3 to 4.6 g/kg of milk produced.
      When ME provided by the diet is less than that needed to fuel maximum milk
      synthesis, however, the dietary amino acid needs of genetically lean sows may be
      reduced because of their inability to mobilize sufficient body fat stores.

PMID- 9581935
TI  - Effects of species raw material source, ash content, and processing temperature
      on amino acid digestibility of animal by-product meals by cecectomized roosters
      and ileally cannulated dogs.
AB  - We conducted experiments to determine amino acid (AA) digestibility of nine
      animal by-product meals using precision-fed cecectomized roosters and ileally
      cannulated dogs. The products initially evaluated in roosters were meat and bone
      meals (MBM) containing 24 or 34% ash, poultry by-product meals (PBP) containing 7
      or 16% ash, lamb meals (LM) containing 15 or 24% ash, a LM analog containing a
      mixture of LM and turkey meal, and two MBM processed at either a low or high
      temperature. The MBM and PBP differing in ash, low-ash LM, and low-temperature
      MBM then were incorporated into extruded dry dog foods and evaluated in
      cecectomized roosters and ileally cannulated dogs. True digestibility of total AA
      in roosters averaged 76% for the nine meals fed alone, with the low-temperature
      MBM being highest at 84% and the low-ash LM being lowest at 66% (P < .05). No
      consistent differences in rooster AA digestibility were observed between pairs of
      meals differing in ash content. Digestibilities of AA were higher in the low
      temperature MBM than in the high-temperature MBM. Differences in rooster AA
      digestibility values among the six extruded dog foods containing selected animal
      meals were similar to those observed when the animal meals were fed alone. The
      ileally cannulated dog assay yielded results for AA digestibilities that were
      highly correlated (r = .87 to .92) with those of the rooster assay, whereby the
      high-ash MBM and low-temperature MBM foods had the highest mean AA digestibility
      at 82% and the low-ash LM food had the lowest mean AA digestibility at 62% (P <
      .05). Again, no consistent differences in AA digestibilities for dogs were
      observed between pairs of dog foods containing MBM or PBP differing in ash
      content. Results of this study indicated that processing temperature influenced
      AA digestibility of MBM, but species raw material source and ash content had no
      consistent effect on AA digestibility. Results also indicated that the precision
      fed cecectomized rooster assay could be used to predict differences in AA
      digestibility among animal by-product meals for dogs.

PMID- 9581936
TI  - Influence of dietary factors on the pH and ammonia emission of slurry from
      growing-finishing pigs.
AB  - We investigated the effects of dietary factors on the pH and the ammonia emission
      from slurry of growing-finishing pigs. Sixteen male hybrid pigs (80 to 90 kg BW)
      were allotted to one of four diets based on barley-wheat, tapioca, barley
      tapioca, and sugar beet pulp. Diets were formulated to have similar NE and CP
      contents and a similar lysine:NE ratio. Diets differed in nonstarch
      polysaccharide content (NSP) and dietary electrolyte balance (dEB). Urine and
      feces were daily collected quantitatively in metabolism cages and mixed as a
      slurry at the end of the collection period. After mixing, the pH and the ammonia
      emission from the slurry were measured daily in a laboratory setup for 7 d at 20
      degrees C. The type of diet affected the pH of the slurry and the ammonia
      emission (P < .001). The pH of the slurry from pigs fed the sugar beet pulp-based
      diet was .8 unit lower and ammonia emission was 52 to 53% lower than that of the
      other three diets. The low dEB and high NPS sugar beet pulp-based diet increased
      the VFA concentration and reduced the pH and ammonia emission from the slurry. We
      conclude that dietary NSP and dEB influence the pH and ammonia emission from
      slurry of growing-finishing pigs.

PMID- 9581937
TI  - Circadian and ultradian variation in pancreatic secretion of meal-fed pigs after
      weaning.
AB  - We studied the time structure of pancreatic secretion in two experiments
      involving seven 6- to 7-wk-old intact male pigs, surgically fitted with a jugular
      vein catheter for blood sampling, pancreatic catheter, and a duodenal T-cannula
      for chronic pancreatic juice sampling for 72 h at 30- to 60-min intervals. Pigs
      were kept in metabolic cages in a regimen of 12 h of light alternating with 12 h
      of darkness and were fed at 0800, 1500, and 2200 daily a standard diet based on
      barley, soybean meal, and fish meal. Beginning 4 d after surgical recovery, three
      24-h collections of pancreatic juice and blood sampling were begun either at 0700
      or 0800 every 2nd d for 5 d. Pancreatic secretion exhibited a pattern
      characterized by distinct meal-related secretions of the first phase
      (postprandial), containing large amounts of protein and enzymes (trypsin and
      chymotrypsin), and by non-food-stimulated secretions of the second phase with
      less protein and enzymes. During the dark span, the first phase was practically
      absent; the response of the pancreatic secretion to the 2200 meal was not very
      pronounced. Apart from the anticipated circadian rhythm demonstrable by single
      cosinor analysis on a group basis, a prominent 8-h component was almost
      invariably statistically significant. Moreover, an approximately 3.43-h component
      was also prominent. These data indicate that pancreatic secretions are circadian
      periodic and that their response to a standard meal is also circadian-stage
      dependent. The circadian components may have been free-running because the pigs
      were adjusting themselves to the changing phase and that resulted in the period
      being different from exactly 24 h.

PMID- 9581938
TI  - Tissue swainsonine clearance in sheep chronically poisoned with locoweed
      (Oxytropis sericea).
AB  - Locoweed poisoning is seen throughout the world and annually costs the livestock
      industry millions of dollars. Swainsonine inhibits lysosomal alpha-mannosidase
      and Golgi mannosidase II. Poisoned animals are lethargic, anorexic, emaciated,
      and have neurologic signs that range from subtle apprehension to seizures.
      Swainsonine is water-soluble, rapidly absorbed, and likely to be widely
      distributed in the tissues of poisoned animals. The purpose of this study was to
      quantify swainsonine in tissues of locoweed-poisoned sheep and determine the rate
      of swainsonine clearance from animal tissues. Twenty-four crossbred wethers were
      gavaged with ground Oxytropis sericea to obtain swainsonine doses of 1 mg
      swainsonine x kg(-1) BW x d(-1) for 30 d. After dosing, the sheep were killed on
      d 0, 1, 2, 3, 4, 6, 14, 30, 60, and 160. Animal weights and feed consumption were
      monitored. Serum was collected during dosing and withdrawal periods, and tissues
      were collected at necropsy. Serum swainsonine concentrations were determined
      using an alpha-mannosidase inhibition assay. Swainsonine concentrations in
      skeletal muscle, heart, brain, and serum were similar at approximately 250 ng/g.
      Clearance from these tissues was also similar, with half-lives (T(1/2)) of less
      than 20 h. Swainsonine at more than 2,000 ng/g, was detected in the liver,
      spleen, kidney, and pancreas. Clearance from liver, kidney, and pancreas was
      about T(1/2) 60 h. These findings imply that poisoned sheep have significant
      tissue swainsonine concentrations and animals exposed to locoweed should be
      withheld from slaughter for at least 25 d (10 T(1/2)) to ensure that the locoweed
      toxin has cleared from animal tissues and products.

PMID- 9581939
TI  - Feeding lactating primiparous sows to establish three divergent metabolic states:
      I. Associated endocrine changes and postweaning reproductive performance.
AB  - We investigated effects of different metabolic states on reproductive performance
      in lactating, primiparous sows. Sows were fed ad libitum (AL; n = 12),
      alimentated via a gastric cannula to 125% of AL feed intake (SA; n = 8), or
      restricted (R; n = 9) to 50% of AL from d 1 to 28 of lactation. At weaning, all
      sows were fed 2.5x maintenance energy requirements until standing heat and then
      fed twice maintenance energy requirement until slaughter. Sow weight, backfat,
      and litter weights were recorded weekly. After weaning, sows were tested twice
      daily for the onset of estrus and inseminated twice using pooled semen. At d 28
      of gestation, sows were slaughtered, and the reproductive tracts were recovered
      to determine ovulation rate and embryo survival. Intensive blood sampling was
      performed before and after weaning for 12-h periods to characterize changes in
      plasma LH, insulin, and IGF-I. After weaning, additional samples were taken to
      monitor changes in LH and progesterone. Insulin and IGF-I were determined at
      standing heat. During lactation, AL and R sows lost, whereas SA sows gained, body
      weight and backfat (P < .001). Litter growth rates did not differ among
      treatments. Although plasma insulin was not different among treatments, plasma
      IGF-I concentration was lower (P < .001) in R sows. Mean LH and pulse frequency
      before (P < .03 and P < .06, respectively) and after (P < .001; for both) weaning
      were lower in R than in AL or SA sows. After weaning, SA sows lost more weight (P
      < .01) and backfat (P < .01) and ate less feed (P < .001) than AL or R sows. At
      standing heat, no differences in plasma IGF-I or insulin were observed, although
      energy balance for SA sows was lower (P < .01) than for AL or R sows. Weaning-to
      estrus interval was extended (P < .02) in R sows. We observed no treatment
      difference in ovulation rate or embryo survival. Our results demonstrate that
      making sows anabolic during lactation did not ameliorate the negative impact of
      the suckling stimulus or improve fertility after weaning.

PMID- 9581940
TI  - Feeding lactating primiparous sows to establish three divergent metabolic states:
      II. Effect on nitrogen partitioning and skeletal muscle composition.
AB  - We established an experimental model to study nitrogen (N) partitioning in
      lactating primiparous sows alimented to three levels of nutrient intake. Thirty
      six sows fitted with a gastric cannula and fed a 15.4 MJ DE/kg and 18.6% CP diet
      were allocated to one of three treatments after farrowing: 1) ad libitum-fed; 2)
      restricted-fed to 55% of the ad libitum feed intake; and 3) superalimented to at
      least 125% of the ad libitum feed intake. These feed intakes were successfully
      achieved throughout lactation. Nitrogen balance was studied for three 5-d periods
      starting on d 2, 11, and 19 of lactation, and a triceps muscle biopsy was taken
      on d 26. For all treatments, N intake increased, milk N production increased,
      urinary N losses decreased, but fecal N losses increased as the 28-d lactation
      progressed. Restricted-fed sows had the lowest fecal N and urinary losses and
      mobilized the most maternal protein (-23.0 vs -7.4 +/- 6.5 g N/d for ad libitum
      fed sows) during lactation. As a consequence of these economies, and extensive
      protein mobilization, restricted-fed sows were able to maintain milk N production
      similar to that of sows on the other treatments. Superalimented sows did not
      mobilize protein, had the poorest protein digestibility, directed the least
      digestible N toward milk (40.1 vs 78.3% in restricted-fed sows), and produced
      amounts of milk N similar to those produced by sows on the other treatments. The
      treatment differences in N retention measured by N balance were reflected in
      differences in skeletal muscle variables and urinary creatinine. Skeletal muscle
      cell size (protein:DNA ratio) and protein synthetic capacity (RNA:DNA ratio)
      increased in response to feed intake. The protein:DNA ratio increased (P < .01)
      linearly and the RNA:DNA ratio increased (P < .05) in a curvilinear manner. These
      data suggest that primiparous sows partition additional retained N toward their
      maternal reserves rather than milk N. They also suggest that sows fed inadequate
      N intakes maintain milk production by mobilizing maternal protein reserves. Such
      sows also conserve maternal N during lactation, possibly by reducing muscle
      protein synthesis.

PMID- 9581941
TI  - Feeding lactating primiparous sows to establish three divergent metabolic states:
      III. Milk production and pig growth.
AB  - First-litter sows fitted with stomach cannulas were used to test the hypothesis
      that making gilts anabolic during lactation by providing them with extra
      nutrition would increase milk production and pig growth. Gilts were allocated to
      one of three dietary treatments after farrowing: 1) restricted, sows were fed 50%
      of their estimated ad libitum intake; 2) ad libitum, sows were encouraged to eat
      as much feed as possible; and 3) superalimented, sows were infused seven times
      daily through their cannula to achieve a 25 to 30% increase in energy intake in
      excess of that achieved by sows fed on an ad libitum basis. Milk production was
      estimated in mid- (d 10 to 15) and late (d 21 to 25) lactation by a modification
      of the isotope dilution technique. Milk production was similar between treatments
      in mid- and late lactation (P > .05), and this was reflected in a similarity in
      weaning litter weight (P = .238). Milk composition was similar also (P > .05)
      between dietary treatments. Superalimentation provided gilts with 38% more energy
      (P < .001) than gilts fed on an ad libitum basis, and they accrued live weight
      (5.1 kg) and backfat (1.8 mm) during lactation (P < .001). These data provide
      evidence that, unlike multiparous sows that show an increase in milk yield when
      made anabolic during lactation, primiparous sows seem to partition extra energy
      into body growth rather than into milk production.

PMID- 9581942
TI  - Effect of bovine follicular fluid from healthy and atretic follicles on follicle
      stimulating hormone-induced production of estradiol by bovine granulosa cells
      cultured in vitro.
AB  - We studied the effects of active factors present in bovine follicular fluid (bFF)
      from large healthy or atretic follicles on steroidogenic capability of cultured
      bovine granulosa cells. Pools of bFF were collected from follicles (> 10 mm;
      abattoir material) and classified individually as being healthy (bFF-healthy) or
      atretic (bFF-atretic). Pools of jugular plasma were used as controls and were
      from heifers bled during the growing (plasma-growing) or the regressing (plasma
      regressing) phase of follicular dominance. Granulosa cells were cultured in serum
      free conditions and under minimal FSH support (.5 ng/mL) for the first 3 d in
      order to maintain their physiological estradiol production in response to FSH.
      Effects of addition of bFF and plasma at final concentrations of 0, 1, or 5% on
      estradiol and progesterone production and on the percentage of apoptotic cells
      were determined on d 4 of culture following stimulation of granulosa cells with
      either 2 or 6 ng/mL FSH. In a parallel experiment, evaluation of 17beta
      hydroxysteroid dehydrogenase (17beta-HSD) activity was measured following
      addition of bFF. In contrast to plasma, addition of bFF pools decreased (P <
      .001) the FSH-induced estradiol production. Such suppression occurred in a dose
      related manner (P < .05) and to a greater extent (P < .001) following addition of
      bFF from atretic than from healthy follicles. The FSH-induced progesterone
      production was not affected (P > . 1) by addition of bFF but was stimulated (P <
      .05) by that of plasma. Follicle-stimulating hormone decreased (P < .001) the
      percentage of apoptotic granulosa cells and this effect was further enhanced (P <
      .001) by addition of 1 or 5% bFF. The source of bFF did not affect (P > . 1) the
      percentage of apoptotic cells measured at the end of the culture period. On d 4,
      treatment with bFF increased (P < .001) granulosa cell androstenedione conversion
      into testosterone. Results of the present study indicate that factors contained
      in bFF can suppress granulosa cell estradiol production, and the suppressive
      effect varies according to the degree of atresia of the follicle from which the
      fluid has been harvested.

PMID- 9581943
TI  - Ontogeny of insulin-like growth factors (IGF), IGF binding proteins, IGF
      receptors, and growth hormone receptor mRNA levels in porcine pancreas.
AB  - We examined the ontogeny of mRNA levels of IGF-I and -II, IGF type 1 (IGFI-R) and
      type II receptors (IGFII-R), IGF binding protein-1 and -3 (IGFBP-1 and -3), GH
      receptor (GHR), and tissue concentrations of IGF and IGFBP in the pancreas of
      pigs. Tissues were collected from fetuses at 90 and 110 d of gestation and from
      pigs at 1, 21, 90 and 180 d of age. Northern blots were performed using total RNA
      hybridized with 32P-labeled cDNA probes (human IGF-I and human IGFI-R) and cRNA
      probes (rat IGF-II, human IGFII-R, human IGFBP-1, pig IGFBP-3, and pig GHR).
      There were two accelerated growth stages of the pancreas: the first one at 90 d
      of fetal life, which is characterized by cell hyperplasia (high ratio of DNA to
      body weight), and the second one at postnatal 90 d, which is attributed to cell
      hypertrophy (high ratios of pancreatic weight, RNA, and protein to DNA). The
      level of IGF-II mRNA and its tissue concentration were predominant during fetal
      life and low thereafter. The IGF-I mRNA level was high during fetal and early
      postnatal life and decreased thereafter. Messenger RNA levels of IGFI-R, IGFBP-3,
      and GHR and concentrations of IGFBP-1 and -2 were abundant during fetal and early
      postnatal life. In conclusion, IGF may be involved in various physiological
      periods of pancreatic development in pigs.

PMID- 9581944
TI  - Generation times of Epidinium caudatum and Entodinium caudatum, determined in
      vitro by transferring at various time intervals.
AB  - Generation times were determined in vitro with a pure culture of Epidinium
      caudatum and a mixed culture of Epidinium caudatum and Entodinium caudatum.
      Measurement of logarithmic growth from a small inoculum for Epidinium caudatum
      alone, or in coculture, resulted in generation times of 30.8 and 19.5 h,
      respectively. Epidinium concentrations, either alone or in coculture, were
      maintained when cultures were transferred every 12 h; however, concentrations
      decreased rapidly with transfers at 4, 6, or 8 h. For Entodinium caudatum, a
      generation time of 16.3 h was obtained from measurement of logarithmic growth.
      Based on sequential transfer data at varying time intervals, Epidinium caudatum
      and Entodinium caudatum seem to be capable of doubling in approximately 12 to 13
      h. These values are markedly less than those previously reported and help explain
      the ability of these protozoa to maintain themselves in the rumen.

PMID- 9581945
TI  - Methionine and somatotropin supplementation in growing beef cattle.
AB  - This objective of this study was to determine the effects of supplemental bovine
      somatotropin and supplemental ruminally protected methionine (Met) on ADG, feed
      efficiency (FE), body composition (BC), and serum concentrations of Met, ST, IGF
      I, and progesterone in growing beef cattle. Two experiments were conducted. In
      one experiment, 24 growing beef cattle (6 steers and 18 heifers, 410 +/- 2 kg)
      were divided into two treatment groups, either controls or Met-treated animals.
      In a second experiment, 32 heifers and 8 steers (311 +/- 2 kg) were used in a
      completely randomized design experiment (four treatments; two pens/treatment).
      Treatments were arranged as a 2 x 2 factorial, with main effects of ST (0 or 33
      microg/kg BW per day) and Met (0 or 6 g x animal(-1) x d(-1)). Feed efficiency
      and ADG were not affected by Met. However, ST increased FE and ADG (P < .05).
      Serum Met concentrations tended (P = .08) to increase with Met administration and
      remained unchanged by ST administration. Serum ST and IGF-I concentrations were
      increased (P < .05) by ST administration but unchanged by Met administration. The
      BC and heifer serum progesterone concentrations were similar across treatments,
      and no interactions (P > .10) were observed between ST and Met. In summary, ST
      improved BW gain and FE. Methionine was not the first-limiting AA in the diet
      fed.

PMID- 9581946
TI  - Effect of level and source of dietary selenium on concentrations of thyroid
      hormones and immunoglobulins in beef cows and calves.
AB  - Our objective was to determine the effect of level and chemical form of dietary
      selenium on productivity of beef cows, concentrations of triiodothyronine (T3),
      and thyroxine (T4) in plasma, and immunoglobulins (IgG and IgM) in plasma and
      colostrum of cows. Pregnant cows (n = 60) were randomly allocated among four
      dietary treatments of 20, 60, or 120 ppm Se as selenite and 60 ppm as
      selenomethionine from selenized yeast (SeY) in salts offered free-choice.
      Treatments began 90 d prepartum and continued through the second parturition.
      Treatments did not affect the final body weights of cows or birth weights or
      weaning weights of calves. At parturition, cows given salt with 20 ppm Se as
      selenite had lower (P < . 05) concentrations of Se in blood than cows with access
      to higher-Se salts. Treatments affected (P < .01) the concentration of T3 and the
      ratio of T3:T4 in plasma of cows. The concentration of T3 in plasma of cows with
      access to salt with 20 ppm Se was 14% lower than that in cows supplemented with
      60 ppm Se as selenite or SeY. Plasma IgG in cows and calves, colostrum, and Se
      concentrations in colostrum, casein, and whey were lowest (P < .01) for cows
      given salt with only 20 ppm Se. Thus, salts with concentrations of 60 and 120 ppm
      Se improved measures of Se status in cows and calves. Consideration should be
      given to the concentrations of T3 and IgG when determining the nutritional
      requirements for Se in cattle.

PMID- 9581947
TI  - Statistical analysis of repeated measures data using SAS procedures.
AB  - Mixed linear models were developed by animal breeders to evaluate genetic
      potential of bulls. Application of mixed models has recently spread to all areas
      of research, spurred by availability of advanced computer software. Previously,
      mixed model analyses were implemented by adapting fixed-effect methods to models
      with random effects. This imposed limitations on applicability because the
      covariance structure was not modeled. This is the case with PROC GLM in the SAS
      System. Recent versions of the SAS System include PROC MIXED. This procedure
      implements random effects in the statistical model and permits modeling the
      covariance structure of the data. Thereby, PROC MIXED can compute efficient
      estimates of fixed effects and valid standard errors of the estimates. Modeling
      the covariance structure is especially important for analysis of repeated
      measures data because measurements taken close in time are potentially more
      highly correlated than those taken far apart in time.

PMID- 9581948
TI  - Apparent ruminal degradation and rumen escape of lysine, methionine, and
      threonine administered intraruminally in mixtures to high-yielding cows.
AB  - We studied the kinetics of lysine, methionine, and threonine in six high-yielding
      dairy cows at peak lactation (stage 1) and 6 mo later (stage 2). The cows were
      fitted with cannulas in the rumen and duodenum and were automatically fed every
      4th h. The three amino acids (AA) were administered intraruminally in mixtures at
      dosages of 100, 200, 300, and 400 mmol of each, together with polyethylene glycol
      (PEG) as a liquid marker. Mean rumen liquid pools at stages 1 and 2 were not
      significantly different. The mean liquid outflow decreased from 13.6 to 9.5 L/h,
      and there was a significant linear increase in the liquid outflow with increasing
      dosages of AA. No significant interaction was found between feeding levels and AA
      dosages on rates of apparent degradation and rumen escape values. Expressed as
      percentages of the dosage, all three AA studied showed a significant linear
      decrease in degradation and a significant increase in rumen escape values with
      increasing dosage. At the feeding levels in stages 1 and 2, the highest relative
      degradation rates (percentage of dosage) were observed for threonine. The
      relative degradation rate of methionine was significantly lower than of lysine at
      the high feeding level but significantly higher at the low feeding level. The
      mean rumen escape values of threonine, methionine, and lysine across dosages and
      feeding levels were 16.7, 22.1, and 20.5%, respectively. The flow of the
      administered AA into the duodenum during an 8-h period after administration
      increased with increasing dosages, with peak concentrations after 1 h. Thus, the
      amounts of rumen escape of the three AA were considerable at all dosages, even
      when the AA were administered in unprotected form.

PMID- 9581949
TI  - Rapid communication: mapping of the porcine Colipase gene to chromosome 7 using
      linkage analysis.

PMID- 9581950
TI  - Effect of shock waveform on relationship between upper limit of vulnerability and
      defibrillation threshold.
AB  - INTRODUCTION: The upper limit of vulnerability (ULV) correlates with the
      defibrillation threshold (DFT). The ULV can be determined with a single episode
      of ventricular fibrillation and is more reproducible than the single-point DFT.
      The critical-point hypothesis of defibrillation predicts that the relation
      between the ULV and the DFT is independent of shock waveform. The principal goal
      of this study was to test this prediction. METHODS AND RESULTS: We studied 45
      patients at implants of pectoral cardioverter defibrillators. In the monophasic
      biphasic group (n = 15), DFT and ULV were determined for monophasic and biphasic
      pulses from a 120-microF capacitor. In the 60- to 110-microF group (n = 30), DFT
      and ULV were compared for a clinically used 110-microF waveform and a novel 60
      microF waveform with 70% phase 1 tilt and 7-msec phase 2 duration. In the
      monophasic-biphasic group, all measures of ULV and DFT were greater for
      monophasic than biphasic waveforms (P < 0.0001). In the 60- to 110-microF group,
      the current and voltage at the ULV and DFT were higher for the 60-microF waveform
      (P < 0.0001), but stored energy was lower (ULV 17%, P < 0.0001; DFT 19%, P =
      0.03). There was a close correlation between ULV and DFT for both the monophasic
      biphasic group (monophasic r2 = 0.75, P < 0.001; biphasic r2 = 0.82, P < 0.001)
      and the 60- to 110-microF group (60 microF r2 = 0.81 P < 0.001; 110 microF r2 =
      0.75, P < 0.001). The ratio of ULV to DFT was not significantly different for
      monophasic versus biphasic pulses (1.17 +/- 0.12 vs 1.14 +/- 0.19, P = 0.19) or
      60-microF versus 110-microF pulses (1.15 +/- 0.16 vs 1.11 +/- 0.14, P = 0.82).
      The slopes of the ULV versus DFT regression lines also were not significantly
      different (monophasic vs biphasic pulses, P = 0.46; 60-microF vs 110-microF
      pulses, P = 0.99). The sample sizes required to detect the observed differences
      between experimental conditions (P < 0.05) were 4 for ULV versus 6 for DFT in the
      monophasic-biphasic group (95% power) and 11 for ULV versus 31 for DFT in the 60-
      to 110-microF group (75% power). CONCLUSION: The relation between ULV and DFT is
      independent of shock waveform. Fewer patients are required to detect a moderate
      difference in efficacy of defibrillation waveforms by ULV than by DFT. A small
      capacitor biphasic waveform with a long second phase defibrillates with lower
      stored energy than a clinically used waveform.

PMID- 9581951
TI  - Effect of shock polarity on biphasic defibrillation thresholds using an active
      pectoral lead system.
AB  - INTRODUCTION: The downsizing of implantable defibrillator pulse generators has
      made pectoral placement routine. A further reduction of defibrillation thresholds
      (DFTs) may simplify implantation defibrillation testing and allow for smaller,
      lower output pulse generators while maintaining an adequate defibrillation safety
      margin. One factor that may affect defibrillation efficacy is shock polarity.
      METHODS AND RESULTS: Sixty consecutive patients undergoing dual-coil, active left
      pectoral defibrillator implantation were evaluated. Paired, biphasic DFTs were
      measured in normal (RV apex = cathode) and reverse (RV apex = anode) polarity
      with order of testing randomized. Reverse polarity conferred a 15% reduction of
      mean DFTs (8.5 +/- 5.0 J normal, 7.2 +/- 4.6 J reverse polarity, P = 0.02). The
      effect of polarity appeared most pronounced among the patients with a high DFT (>
      or = 15 J) resulting in a 31% reduction with reverse polarity (16.7 +/- 2.5 J
      normal, 11.5 +/- 5.9 J reverse, P = 0.03). CONCLUSION: Reversing shock polarity
      results in significantly lower biphasic DFTs with an active pectoral lead system,
      particularly in the subgroup of patients with a high normal polarity threshold.
      Reversing polarity in these patients may simplify acute defibrillation testing
      and allow for lower output devices.

PMID- 9581952
TI  - Focal atrial tachycardia: reanalysis of the clinical and electrophysiologic
      characteristics and prediction of successful radiofrequency ablation.
AB  - INTRODUCTION: Reports about the clinical and electrophysiologic characteristics
      of focal atrial tachycardia vary widely. Furthermore, the impact of age, gender,
      associated cardiac diseases, mechanism, location of atrial tachycardia, and the
      prediction of results of radiofrequency catheter ablation was not clear. The
      purpose of this study was to further understand the clinical and
      electrophysiologic characteristics of focal atrial tachycardia and the prediction
      of results of radiofrequency ablation. METHODS AND RESULTS: We searched the
      literature published between January 1969 and July 1997 using the key word
      "atrial tachycardia" from the MEDLINE and National Library of Medicine systems.
      The items analyzed were age, sex, cardiac disease, mechanism, attack pattern,
      cycle length, location, number of atrial tachycardias, results of ablation, and
      recurrence after ablation. Multivariate analysis showed that age and paroxysmal
      type of tachycardia were independent predictors of nonautomatic mechanism; age
      and presence of other cardiac diseases were independent predictors of multiple
      atrial tachycardias, and age also was the independent predictor of right-sided
      atrial tachycardia. Atrial tachycardia located in the right atrium was the only
      significant predictor of successful radiofrequency catheter ablation. Other
      cardiac diseases and multiple atrial tachycardias were the significant predictors
      of recurrence after initial successful radiofrequency catheter ablation.
      CONCLUSION: Patient age is closely related to the clinical and electrophysiologic
      characteristics of atrial tachycardia based on our reanalysis, which found that
      patient age is an independent predictor of nonautomatic mechanism, right atrial
      location, existence of multiple atrial tachycardias, and recurrence of atrial
      tachycardia after initial successful ablation.

PMID- 9581953
TI  - Divergent effect of acute ventricular dilatation on the electrophysiologic
      characteristics of d,l-sotalol and flecainide in the isolated rabbit heart.
AB  - INTRODUCTION: The interaction between acute ventricular dilatation (AVD) as one
      aspect of ventricular dysfunction and Class I and III antiarrhythmic drugs is
      uncertain. We therefore investigated the effects of AVD on the electrophysiologic
      properties of d,l-sotalol and flecainide. METHODS AND RESULTS: The isolated
      rabbit heart was used as a model of AVD. The ventricular size and, therefore, the
      diastolic pressure were modified by sudden volume changes of a fluid-filled
      balloon placed in the left ventricle. Pacing was performed alternately using epi-
      and endocardial monophasic action potential (MAP)-pacing catheters at cycle
      lengths from 1,000 to 300 msec. d,l-Sotalol (10 microM) resulted in a significant
      (P < 0.05) lengthening of refractoriness (+13.5% +/- 3.1%), MAP duration (+14.9%
      +/- 3.2%), and QT interval (+15.5% +/- 4.1%) (mean +/- SEM at 1,000 msec). These
      effects had a reverse rate-dependence. AVD to a diastolic pressure of 30 mmHg
      reduced refractoriness and left ventricular MAP duration. In comparison with the
      control group with the same extent of AVD, d,l-sotalol still led to a significant
      prolongation of repolarization for all cycle lengths except 300 msec, so that its
      effects were not absolutely but relatively preserved. In contrast, flecainide (2
      microM) had no significant effects on refractoriness or MAP duration. It led to a
      significant, rate-dependent increase of pacing thresholds (+47.6% +/- 8.2%),
      prolongation of QRS (+48.8% +/- 5.6%), and conduction time (+78.6% +/- 8.6%)
      (mean +/- SEM at 300 msec). In the flecainide group, AVD significantly increased
      the normal rate-dependent prolongation of QRS (+16.7% +/- 5.5%) and conduction
      time (+17.1% +/- 4.3%). CONCLUSION: Our data demonstrate that, during AVD, the
      Class III effect of d,l-sotalol is preserved, whereas flecainide's effect of
      slowing conduction is exaggerated. This may contribute to flecainide-related
      proarrhythmia in certain clinical situations.

PMID- 9581954
TI  - Syncytial heterogeneity as a mechanism underlying cardiac far-field stimulation
      during defibrillation-level shocks.
AB  - INTRODUCTION: The mechanisms by which a defibrillation shock directly stimulates
      regions of cardiac tissue distal to the stimulus electrodes ("far-field"
      stimulation) are still not well understood. Existing hypotheses have proposed
      that intercellular discontinuities and/or fiber curvatures induce the requisite
      membrane polarizations. This article hypothesizes a third potential mechanism:
      one based on the existence and influences of syncytial (anatomic) heterogeneities
      inherent throughout the bulk myocardium itself. METHODS AND RESULTS: We simulated
      the effects of such heterogeneities in a model of a two-dimensional region of
      passive cardiac tissue subjected to uniform 1 V/cm longitudinal or transverse
      field stimuli. Heterogeneities were manifested via random spatial variations of
      intracellular volume fractions (fi) over multiple length scales, with mean fi of
      80% and standard deviation of fi (sigma[fi]) ranging from 0% to 10%. During field
      stimulation, many interspersed and variously shaped and sized islands of
      hyperpolarization and depolarization developed across the tissue, with their
      locations and extents correlated to the spatial gradients of the underlying
      heterogeneities. Increases in sigma(fi) correspondingly increased the shock
      induced magnitudes of resulting membrane polarizations. The ratio of maximal
      polarizations for equivalent longitudinal and transverse shocks approximated 2:1
      across all sigma(fi) tested. At sigma(fi) = 5%, these maximal induced
      polarizations were 17.4 +/- 2.4 mV and 8.18 +/- 1.5 mV, respectively. Assuming an
      excitation threshold of 25 mV, these data suggest corresponding diastolic
      thresholds of 1.47 +/- 0.20 V/cm and 3.14 +/- 0.50 V/cm, respectively.
      CONCLUSION: This study predicts that syncytial heterogeneities inherent within
      cardiac tissue could represent a significant-and heretofore unappreciated
      mechanism underlying field-induced polarizations throughout the bulk myocardium.

PMID- 9581955
TI  - Evidence for multiple atrio-AV nodal inputs in the normal dog heart.
AB  - INTRODUCTION: Complete AV block after combined fast pathway (FP) and slow pathway
      (SP) ablation is uncommon. The purpose of this study was to interrupt activation
      of these and additional inputs by placing a radiofrequency lesion across the
      interatrial septum between the FP and SP ablation sites. METHODS AND RESULTS: In
      eight anesthetized open chest dogs, FP ablation induced significant A-H
      prolongation (deltaA-H: 51 +/- 14 msec; P < 0.001) and a shift of earliest
      retrograde atrial activation from the anterior septum to the region of the
      coronary sinus (CS) os. Subsequently, ablation of the interatrial septum across
      the fossa ovalis was successful in 5 of 8 dogs, changing the sequence of atrial
      activation (A) so that A at the His-bundle electrogram, which initially preceded
      A at the CS os (18 +/- 4 msec vs 46 +/- 7 msec, P < 0.01), now followed CS os A
      (81 +/- 31 msec vs 59 +/- 20 msec, P < 0.05). Additional ablation of the SP
      caused a type II Mobitz AV block or complete AV block in 5 of 8 dogs. The four
      dogs with complete AV block showed a stable, high junctional escape rhythm at a
      rate of 64 +/- 16 beats/min. Pacing between the ablation lesions and the AV node
      in one dog showed 1:1 AV conduction and Wenckebach-type AV block indicating
      preserved AV nodal function. Histology showed necrotic changes in the FP and SP
      transitional cell zones and in the atrial tissue of the interatrial septum.
      However, the compact AV node, His bundle, and adjacent atria and transitional
      cells were undamaged. CONCLUSION: There are additional AV nodal inputs in the
      interatrial septum in addition to the anterior FP and posterior SP inputs.
      Ablation of all of these may be required, if the aim is production of complete AV
      block proximal to the AV node with a high junctional escape rhythm.

PMID- 9581956
TI  - Temperature-controlled irrigated tip radiofrequency catheter ablation: comparison
      of in vivo and in vitro lesion dimensions for standard catheter and irrigated tip
      catheter with minimal infusion rate.
AB  - INTRODUCTION: In patients with ventricular tachycardias due to structural heart
      disease, catheter ablation cures < 60% partly due to the limited lesion size
      after conventional radiofrequency ablation. Irrigated tip radiofrequency ablation
      using power control and high infusion rates enlarges lesion size, but has
      increased risk of cratering. The present study explores irrigated tip catheter
      ablation in temperature-controlled mode, target temperature 60 degrees C, using
      an irrigation rate of 1 mL/min, comparing this to conventional catheter
      technique, target temperature 80 degrees C. METHODS AND RESULTS: In vivo
      anesthetized pigs were ablated in the left ventricle. In vitro strips of porcine
      left ventricular myocardium were ablated in a tissue bath. Lesion volume was
      significantly larger after irrigated tip ablation both in vivo (544 +/- 218 vs
      325 +/- 194 mm3, P < 0.01) and in vitro (286 +/- 113 vs 179 +/- 23 mm3, P <
      0.001). The incidence of cratering was not significantly different between the
      two groups. In vivo, no coagulum formation on part of the catheter tip was seen
      after irrigated tip ablation as opposed to 52% of the applications with
      conventional ablation (P < 0.05). CONCLUSION: We conclude that temperature
      controlled radiofrequency ablation with irrigated tip catheters using low target
      temperature and low infusion rate enlarges lesion size without increasing the
      incidence of cratering and reduces coagulum formation of the tip.

PMID- 9581957
TI  - Functional communication between cardiac ATP-sensitive K+ channel and Na/K
      ATPase.
AB  - INTRODUCTION: Functional interaction between K(ATP) channel and Na/K ATPase was
      studied in single guinea pig ventricular myocytes because both membrane molecules
      are known to be involved in ischemic episodes. METHODS AND RESULTS: K(ATP)
      channel currents were recorded at 36 degrees C by using whole cell, cell
      attached, inside-out, and open cell-attached modes of patch clamp techniques on
      enzymatically isolated ventricular myocytes. In the whole cell mode, ouabain (1
      microM) reversibly inhibited the K(ATP) currents induced by metabolic stress (ATP
      free pipette solution and 1 mM NaCN), but not those activated by cromakalim (100
      microM), a K(ATP) channel opener. In the cell-attached mode, ouabain
      concentration dependently inhibited K(ATP) channel opening induced by metabolic
      suppression (5.5 mM 2-deoxyglucose and 1 mM CN-). Half-inhibition concentration
      for ouabain was 21.0 +/- 5.5 nM and the Hill coefficient was 0.8 +/- 0.1 (n =
      26). However, ouabain did not have an effect on the channel activity induced by
      cromakalim (100 microM). In the inside-out mode, ouabain applied to the internal
      side of membrane did not affect the channel. In the open cell-attached mode made
      by preincubation with streptolysin-O (0.08 U/mL), the K(ATP) channels were not
      activated by the metabolic inhibitors but were by reducing extracellular ATP
      concentrations, because subsarcolemmal ATP concentration could be controlled
      through tiny membrane holes. The channels thus activated were not suppressed by
      ouabain. CONCLUSION: The inhibition of Na/K ATPase by ouabain appeared to block
      the K(ATP) channels by accumulating subsarcolemmal ATP caused by a decrease of
      the transition from ATP to ADP. In the presence of ischemic episodes, the
      administration of digitalis compounds may affect the opening of K(ATP) channels,
      which is primarily protective against the development of irreversible myocardial
      damage.

PMID- 9581958
TI  - Susceptibility to atrial fibrillation: a study in an ovine model of pacing
      induced early heart failure.
AB  - INTRODUCTION: The development of susceptibility to atrial fibrillation (AF) is a
      common consequence of many forms of cardiovascular disease, especially heart
      failure. In this study we used a sheep model of pacing-induced stable early heart
      failure to describe, quantify, and relate the level of susceptibility to AF to
      changes in structural and electrophysiologic parameters. METHODS AND RESULTS:
      Epicardial electrodes were implanted on the atria and right ventricles of nine
      sheep. The AF threshold, atrial vulnerability period, atrial effective refractory
      period (ERP), and interatrial conduction time were examined during control and
      over a 6-week period of ventricular pacing at 190 beats/min. Left atrial (LA)
      area and left ventricular (LV) fractional shortening were monitored using
      echocardiography. There were significant increases in LA susceptibility to AF (P
      < 0.0003), LA area (P < 0.0002), and LA ERP400 (P < 0.0002). Rate of increase in
      LA area was related positively to AF susceptibility (P = 0.02) and inversely to
      LA ERP400 (P = 0.002). LV fractional shortening decreased to approximately 50% of
      control value (P < 0.00001). No changes were observed in right atrial
      electrophysiology. CONCLUSION: In this study, susceptibility (the ability of an
      extrastimulus to induce AF) was rigorously measured within a predetermined
      format. Significant relationships were found to exist between susceptibility,
      certain of the observed changes in atrial electrophysiology and structure.

PMID- 9581959
TI  - Selected slow pathway ablation in a patient with corrected transposition of the
      great arteries and atrioventricular nodal reentrant tachycardia.
AB  - We report the first known case of AV nodal reentrant tachycardia (AVNRT)
      associated with a corrected transposition of the great arteries to be treated
      successfully by ablation of the slow pathway. Triple AV nodal pathways were
      observed in the anterograde direction and two types of AVNRT were induced. Input
      of the fast pathway to the AV node was located at the anterior portion of the
      left-sided AV annulus, while the input of the intermediate and slow pathways was
      located at the anteroseptal portion of the right-sided AV annulus. Radiofrequency
      energy ablation at the right anteroseptal site eliminated the intermediate and
      slow pathways.

PMID- 9581960
TI  - Recurrent supine syncope: an unusual manifestation of the neurally mediated
      faint.
AB  - INTRODUCTION: Syncope occasionally may occur in the supine patient due to severe
      brady- or tachyarrhythmia. However, recurrent syncope upon assumption of the
      supine position as a result of a neurally mediated reflex mechanism has not been
      reported previously. METHODS AND RESULTS: Two young patients, both of whom had
      significant systemic illnesses, experienced recurrent episodes of presyncope
      and/or syncope shortly after assuming the supine position. During ambulatory ECG
      monitoring, symptoms were provoked only by lying down and were associated with
      transient bradycardia. Head-up tilt table testing was undertaken as part of the
      syncope evaluation and was nondiagnostic in both cases. However, both patients
      exhibited a transient cardioinhibitory response with reproduction of typical
      symptoms upon return of the table to the supine position ("reverse tilt"). During
      follow-up (8 and 14 months), both patients improved with pharmacologic treatment
      (disopyramide in one case and midodrine in the other). CONCLUSION: Presyncope or
      syncope upon lying down can be an unusual manifestation of the neurally mediated
      faint.

PMID- 9581961
TI  - Arrhythmia of the month: shortening of ventriculoatrial conduction time during
      radiofrequency catheter ablation of a concealed accessory pathway.

PMID- 9581962
TI  - Mahaim pathway.

PMID- 9581963
TI  - Double blind test of magnetic field effects on neurite outgrowth.
AB  - Previous work reported that nerve growth factor-stimulated neurite outgrowth in
      PC-12 cells could be altered by exposure to parallel alternating current (AC) and
      direct current (DC) magnetic fields under a variety of exposure conditions,
      producing results that are consistent with the predictions of the ion parametric
      resonance (IPR) model. The credibility of these results, considered extraordinary
      by some scientists, could be strengthened if the cell response were found to
      persist under alternate assay conditions. We replaced part of our standard assay
      procedure with a double blind procedure. This new procedure obscured 1) whether a
      particular set of dishes of cells was exposed or not, and 2) which individual
      dish was in which exposure system. The goal was to determine whether the
      previously observed responses of PC-12 cells to magnetic fields would be
      sufficiently robust to decode the imposed blinding, thereby removing any question
      of experimenter bias in reported results. We placed three coded dishes of cells
      in each of two otherwise identical exposure systems, one not energized and one
      energized to produce exposure conditions predicted to maximally suppress neurite
      outgrowth (Bdc of 36.6 microT, parallel 45 Hz AC of 23.8 microT rms). Each of the
      six dishes were recoded before assay to further obscure the exposure identity of
      any individual dish. The combined results of four distinct runs of these double
      blind experiments unequivocally demonstrated that 1) there was a clear,
      distinctive, repeatable consistency with the actual energization of the exposure
      systems and location of each dish, and with the predictions of the IPR model; 2)
      only the explicitly stated experimental variables influenced the experiment; and
      3) the reported response of the cells was very improbably due to chance (P =
      .000024).

PMID- 9581964
TI  - 60 Hz electric fields and incandescent light as aversive stimuli controlling the
      behavior of rats responding under concurrent schedules of reinforcement.
AB  - Several reports have shown that animals will sometimes engage in behaviors that
      reduce their exposure to a 60 Hz electric field (E-field). The field, therefore,
      can function as an aversive stimulus. In other studies, the E-field at equivalent
      strengths failed to function as an aversive stimulus. The present experiment,
      using rats, demonstrates how factors other than field strength can influence
      whether a subject engages in behavior that reduces field exposure. The general
      design consisted of giving the rat a choice between two alternatives, one of
      which sometimes included an added stimulus. Each subject was trained to press
      each of two levers to obtain food. Pressing one lever was reinforced
      intermittently under a variable interval 2 min schedule (VI 2); pressing the
      other lever was reinforced by a second VI 2 schedule operating independently of
      the first. Under this concurrent schedule the rat spent 50% of the daily 50 min
      session responding to each of the levers, indicating that they were equally
      "valued." Next, while the schedules remained in effect, the first response to one
      of the levers turned on a 100 kV/m E-field which remained on until the rat
      pressed the other lever. The time spent responding under the schedule associated
      with the field was reduced by about 5-10%. When the procedure was changed so that
      no lever presses produced food, i.e., extinction, but the added stimulus
      contingency remained, the rats spent even less time in the presence of the field.
      Similar outcomes were observed during both the concurrent food or extinction
      schedules when incandescent light was used. Thus, both an E-field and
      incandescent light functioned as aversive stimuli, but the magnitude of the
      aversiveness was small. Aversiveness depended not only on stimulus intensity, but
      also on behavioral factors.

PMID- 9581965
TI  - Effects of extremely low frequency electromagnetic field (EMF) on collagen type I
      mRNA expression and extracellular matrix synthesis of human osteoblastic cells.
AB  - Human osteoblastic cells were grown in a three-dimensional (3-D) cell culture
      model and used to test the effects of a 20 Hz sinusoidal electromagnetic field
      (EMF; 6 mT and 113 mV/cm max) on collagen type I mRNA expression and
      extracellular matrix formation in comparison with the effects of growth factors.
      The cells were isolated from trabecular bone of a healthy individual (HO-197) and
      from a patient presenting with myositis ossificans (MO-192) and grown in a
      collagenous sponge-like substrate. Maximal enhancement of collagen type I
      expression after EMF treatment was 3.7-fold in HO-197 cells and 5.4-fold in MO
      192 cells. Similar enhancement was found after transforming growth factor-beta
      (TGF-beta) and insulin-like growth factor-I (IGF-I) treatment. Combined treatment
      of the cells with EMF and the two growth factors TGF-beta and IGF-I did not act
      synergistically. MO-192 cells produced an osteoblast-characteristic extracellular
      matrix containing collagen type I, alkaline phosphatase, and osteocalcin,
      together with collagen type III, TP-1, and TP-3, two epitopes of an osteoblastic
      differentiation marker. The data suggest that the effects of EMFs on osteoblastic
      differentiation are comparable to those of TGF-beta and IGF-I. We conclude that
      EMF effects in the treatment of skeletal disorders and in orthopedic adjuvant
      therapy are mediated via enhancement of collagen type I mRNA expression, which
      may lead to extensive extracellular matrix synthesis.

PMID- 9581966
TI  - Thermophysiological responses of human volunteers during controlled whole-body
      radio frequency exposure at 450 MHz.
AB  - Thermoregulatory responses of heat production and heat loss were measured in
      seven adult volunteers (four women and three men, aged 21-57 yr) during 45-min
      dorsal exposures of the whole body to 450 MHz continuous wave radio frequency
      (RF) fields. Two power densities (PD) (local peak PD = 18 and 24 mW/cm2; local
      peak specific absorption rate = 0.320 [W/kg]/[mW/cm2]) were tested in each of
      three ambient temperatures (Ta = 24, 28, and 31 degrees C) plus Ta controls (no
      RF). No changes in metabolic heat production occurred under any exposure
      conditions. Vigorous increases in sweating rate on back and chest, directly
      related to both Ta and PD, cooled the skin and ensured efficient regulation of
      the deep body (esophageal) temperature to within 0.1 degrees C of the normal
      level. Category judgments of thermal sensation, comfort, sweating, and thermal
      preference usually matched the measured changes in physiological responses. Some
      subtle effects related to gender were noted that confirm classic physiological
      data. Our results indicate that dorsal exposures of humans to a supraresonant
      frequency of 450 MHz at local peak specific absorption rates up to 7.68 W/kg are
      mildly thermogenic and are counteracted efficiently by normal thermophysiologic
      heat loss mechanisms, principally sweating.

PMID- 9581967
TI  - Particle deposition onto a human head: influence of electrostatic and wind
      fields.
AB  - This study investigates electrostatic fields surrounding the human head and
      particle deposition onto facial skin and eyes caused by the combined effect of
      electrostatic and wind fields. The electrostatic fields are calculated by a three
      dimensional numerical model calculating the field strength between a field source
      and a human head. The deposition velocity can be viewed as determined by the sum
      of two contributions: that of an electrostatic field and that of a wind field.
      Deposition velocities are calculated by a semiempirical particle deposition model
      that considers particle transport from the free stream to the human face. The
      particle deposition model uses the electrostatic field model results as input
      parameters and is applied to the forehead and eyes of two facial shapes for two
      different turbulence conditions and aerosol charge distributions. The results of
      different practical working conditions, under which the potential difference
      between head (person) and source ranges from 5.6 to 15.0 kV, indicates that the
      presence of electrostatic fields always increases particle deposition for
      industrial aerosols. For aged aerosols an effect is only present for submicron
      particles.

PMID- 9581968
TI  - Complex effects of long-term 50 Hz magnetic field exposure in vivo on immune
      functions in female Sprague-Dawley rats depend on duration of exposure.
AB  - In previous studies we have demonstrated that 50 Hz, 100 microT magnetic field
      (MF) exposure of female Sprague-Dawley rats for 13 weeks significantly enhances
      the development and growth of mammary tumors in a breast cancer model. The
      present study was designed to test the hypothesis that, at least in part, the
      tumor (co)promoting effect of MF exposure is due to MF effects on the immune
      surveillance system, which is of critical importance in protecting an organism
      against the development and growth of tumors. For this purpose, female Sprague
      Dawley rats of the same age as in the mammary tumor experiments were continuously
      exposed for different periods (2, 4, 8, and 13 weeks) to a 50 Hz, 100 microT MF.
      Control groups were sham-exposed simultaneously. Following the different exposure
      periods, splenic lymphocytes were cultured and the proliferative responses to the
      T-cell-selective mitogen concanavalin A (Con A) and the B-cell-selective pokeweed
      mitogen (PWM) were determined. Furthermore, the production of interleukin-1 (IL
      1) was determined in the splenocyte cultures. The mitogenic responsiveness of T
      cells was markedly enhanced after 2 weeks of MF exposure, suggesting a co
      mitogenic action of MF. A significant, but less marked increase in T-cell
      mitogenesis was seen after 4 weeks of MF exposure, whereas no difference from
      sham controls was determined after 8 weeks, indicating adaptation or tolerance to
      this effect of MF exposure. Following 13 weeks of MF exposure, a significant
      decrease in the mitogenic responsiveness of lymphocytes to Con A was obtained.
      This triphasic alteration in T-cell function (i.e., activation, tolerance, and
      suppression) during prolonged MF exposure resembles alterations observed during
      chronic administration of mild stressors, substantiating the hypothesis that
      cells respond to MF in the same way as they do to other environmental stresses.
      In contrast to T cells, the mitogenic responsiveness of B cells and IL-1
      production of PWM-stimulated cells were not altered during MF exposure. The data
      demonstrate that MF in vivo exposure of female rats induces complex effects on
      the mitogenic responsiveness of T cells, which may lead to impaired immune
      surveillance after long-term exposure.

PMID- 9581969
TI  - Involvement of microtubules in the regulation of neuronal growth cone morphologic
      remodeling.
AB  - The guidance of nerve fibers depends on the constant protrusion, movement, and
      retraction (i.e., remodeling) of growth cone lamellae and filopodia. We used
      drugs that interfere with the dynamics of microtubules to investigate the role of
      microtubules in the remodeling of larval amphibian spinal cord neuronal growth
      cones. Vinblastine (8-100 nM), taxol (10 nM), and nocodazole (330 nM) altered
      microtubule distributions in growth cones and decreased the percentage of
      lamellar perimeter undergoing remodeling, while not affecting the rates of
      lamellar protrusion and retraction. Also, 8-20 nM vinblastine caused temporary
      losses of the continuity of the originally fan-shaped lamella, resulting in two
      or more lamellae at the growth cone. At higher concentrations of microtubule
      drugs, the originally fan-shaped lamella broke up into separate smaller lamellae
      followed by the centrifugal displacement from the base of the growth cone and
      eventual collapse of the resultant lamellae. Low doses of cytochalasin B
      prevented the centrifugal displacement of lamellae in response to microtubule
      drugs. During microtubule drug-mediated loss of growth cone lamellae, some
      filopodia were observed to elongate to greater than normal lengths. Similarly,
      exposure to 20 nM vinblastine resulted in an increase in filopodial length but
      not filopodial number. As evidenced by DiOC6(3) staining, 8-20 nM vinblastine
      altered the distribution of membranous organelles within growth cones, suggesting
      that the effects of microtubule drugs on growth cones may be mediated in part by
      alterations in organelle localization. Our data show that microtubules are
      involved in the maintenance and regulation of lamellar and filopodial structures
      at the neuronal growth cone. These findings have implications for the mechanisms
      by which growth cones are guided during development and regeneration.

PMID- 9581970
TI  - Region-specific expression of cyclin-dependent kinase 5 (cdk5) and its
      activators, p35 and p39, in the developing and adult rat central nervous system.
AB  - The ubiquitously expressed cyclin-dependent kinase 5 (cdk5) is essential for
      brain development. Bioactivation of cdk5 in the brain requires the presence of
      one of two related regulatory subunits, p35 and p39. Since either protein alone
      can activate cdk5, the significance of their coexistence as cdk5 kinase
      activators is unclear. To determine whether the two activators are expressed in
      different cells throughout the nervous system and during development, we compared
      the tissue distributions of cdk5, p35, and p39 mRNAs in the rat using in situ
      hybridization. In the adult rat, expression levels of p35 mRNA are generally
      higher in the brain than in the spinal cord, while the converse is observed for
      p39 mRNA. During neurogenesis, both p35 and p39 transcripts can be detected as
      early as embryonic day 12 (E12) in the marginal zone, but are absent from the
      ventricular zone, which may restrict cdk5 activation to the postmitotic neural
      cells in the developing brain. The expression levels of p35 and p39 mRNAs in the
      marginal zone increase by E15 and E17, paralleling the neurogenetic timetable.
      One exception is in the rostral forebrain, where p35 mRNA expression levels are
      high, suggesting that p35 may be the major activator for cdk5 during
      telencephalic morphogenesis. A significant level of p35 mRNA is present in the
      myotome at E12 and p35 expression persists in the premuscle mass and mature
      musculature at later stages, suggesting that p35 may also activate cdk5 during
      myogenesis.

PMID- 9581971
TI  - Characterization of neuronal regeneration in the abdominal ganglion of Aplysia
      californica.
AB  - The ability of neurons in the abdominal ganglion of Aplysia to regenerate their
      axons following branchial nerve crush was studied using retrograde staining and
      intracellular dye injection. The duration of the gill withdrawal reflex (GWR) was
      measured prior to and following nerve crush. Three days after crushing the nerve,
      the duration of the gill withdrawal reflex was reduced to 20% of control levels.
      There was rapid recovery 19 days after crushing the branchial nerve. The GWR
      duration returned to control levels by postlesion days 25-27. Some of the
      behavioral recovery can be attributed to axonal regeneration. Regeneration, as
      evidenced by retrograde staining, was first observed by postlesion day 15. The
      number of stained neurons in ganglia with crushes increased until postlesion day
      33. The number of stained neurons in experimental animals was always less than
      that of controls (67+/-9% at postlesion day 56). More axonal regeneration was
      seen in the hemiganglion ipsilateral to the branchial nerve. Regeneration after
      32 days postlesion was 60+/-5% of controls in the ipsilateral hemiganglion, as
      opposed to 29+/-6% in the contralateral hemiganglion. Regeneration of individual
      neurons was also demonstrated. Identified neuron R2 was shown by intracellular
      dye injection and electrical stimulation of antidromic action potentials to have
      an axon in the branchial nerve in all ganglia allowed to regenerate for longer
      than 32 days. These results indicate that in Aplysia, despite behavioral
      recovery, complete axonal regeneration does not occur in a large segment of the
      neurons in the adult central nervous system.

PMID- 9581972
TI  - Sympathetic nerve contact causes maturation of mast cells in vitro.
AB  - Using a tissue culture model developed to study interactions between peripheral
      neurons and mast cells (MC), time-lapse microscopy showed that RBL-2H3 cells (a
      model of the mucosal MC) formed attachments with sympathetic neurons, ceased to
      divide, and moved along neurites toward the cell bodies. Electron microscopy
      showed significant increase in granules compared to intrinsic controls (RBL cells
      in coculture but lacking neurite contact). In studies using cohort cultures of 12
      to 14-day-old sympathetic neurons, RBL cells adhered more rapidly to neurons
      than did control YB2/0 cells (a neutral target cell), and were inhibited in
      growth compared with RBL cells cultured in parallel without neurons. RBL cells
      cocultured with neurons for 24-48 h took up significantly more 3H-5HT and
      released a significantly larger percentage of 3H-5HT in response to the calcium
      ionophore A23187 than RBL cells in parallel pure cultures. Since no change in MC
      phenotype was seen, we conclude that contact with nerve membrane may be a
      developmental cue leading to maturation of MC.

PMID- 9581973
TI  - A novel neuropeptide precursor gene is expressed in the terrestrial snail central
      nervous system by a group of neurons that control mating behavior.
AB  - We report the isolation of a cDNA clone encoding a neuropeptide precursor named
      preproGFAD from the central nervous system (CNS) of the snail Helix lucorum.
      Analysis of the expression of this gene shows that it is neurospecific and
      expressed in several groups of CNS neurons. Most notable is the expression of
      preproGFAD gene in the right mesocerebrum, where the neurons controlling mating
      behavior are located. The expression in this particular region is observed in
      adult animals but not in juvenile ones. The preprohormone is 108 amino acids long
      and contains a hydrophobic leader peptide and eight Lys-Arg recognition sites for
      endoproteolysis. The post-translational processing of the prohormone may lead to
      the generation of seven tetrapeptides, Gly-Phe-Ala-Asp-COOH (GFAD). This peptide
      has the same sequence as two previously isolated peptides from a related snail,
      Achatina fulica. The first of them (achatin-I) contains D-Phe; the second
      (achatin-II) is its L-Phe-containing stereoisomer. Injection of synthetic D-GFAD
      in nanomolar concentrations into intact animals caused an increase of the
      heartbeat rate and opening of the genital atrium. In preparations containing CNS
      with intact innervation of reproductive organs, bath application of D-GFAD caused
      extensive movements of the penis but not of other reproductive organs.
      Intracellular activation of individual neurons expressing the preproGFAD gene
      also elicited penis movements. D-GFAD also suppressed activity of neurons
      modulating feeding behavior. Our data therefore indicate that the preproGFAD gene
      encodes the precursor of a neuropeptide that participates in the regulation of
      male mating behavior.

PMID- 9581974
TI  - Contact-dependent regulation of N-type calcium channel subunits during
      synaptogenesis.
AB  - The developmental regulation of the N-type calcium channel during synaptogenesis
      was studied using cultured rat hippocampal neurons to elucidate the roles of
      extrinsic versus intrinsic cues in the expression and distribution of this
      channel. Prior to synapse formation, alpha1B and beta3 subunits of the N-type
      calcium channel were distributed diffusely throughout neurites, growth cones, and
      somata. As synaptogenesis proceeded, the subunit distributions became punctate
      and colocalized with the synaptic vesicle protein synaptotagmin. Isolated neurons
      were also examined to test for the requirement of extrinsic cues that control N
      type calcium channel expression and distribution. These neurons expressed N-type
      calcium channel subunits, but their distributions remained diffuse. Functional
      omega-conotoxin GVIA-sensitive channels were expressed in isolated neurons,
      although the distribution of alpha1B subunits was diffuse. The distribution of
      the alpha1B subunit and synaptotagmin only became punctate when neuron-neuron
      contact was allowed. Thus, the expression of functional N-type calcium channels
      is the result of an intrinsic program while extrinsic regulatory cues mediated by
      neuron-neuron contact are required to control their distribution during
      synaptogenesis.

PMID- 9581975
TI  - Glutamate receptor GluR1 expression is altered selectively by chronic audiogenic
      seizures in the Frings mouse brain.
AB  - The audiogenic seizure-susceptible mouse, Frings, is genetically susceptible to
      sound-induced seizures and provides a reliable model of reflex epilepsy that
      lasts throughout the life span of the animal. We used immunohistochemistry to
      examine if the expression of the non-N-methyl-D-aspartate glutamate receptor
      (GluR) subunits GluR1, GluR2, or GluR3 were altered subsequent to multiple
      seizures. Following a regimen of one seizure per day for 3 weeks, GluR1
      immunoreactivity, but not GluR2 or GluR3, was substantially elevated in the outer
      shell of the nucleus accumbens in 21 of 31 chronically seized Frings mice. No
      other brain regions such as the hippocampus exhibited any qualitative changes in
      expression of these subunits. In 9 of the 21 Frings mice exhibiting increased
      GluR1, but in none of the controls, bilateral structural lesions were observed in
      the lateral hypothalamus. These results support a model where highly localized
      changes in the expression of GluR1 occur in response to repeated audiogenic
      seizure.

PMID- 9581976
TI  - Expression and androgen regulation of the ciliary neurotrophic factor receptor
      (CNTFRalpha) in muscles and spinal cord.
AB  - We have previously observed that ciliary neurotrophic factor (CNTF) can prevent
      the degeneration of androgen-sensitive perineal motoneurons and their target
      muscles, the bulbocavernosus and levator ani (BC/LA), in perinatal female rats.
      Response to CNTF is dependent on the expression of the alpha component of the
      CNTF receptor (CNTFRalpha). In the present study, we examined the developmental
      profile and androgen regulation of CNTFRalpha gene expression in BC/LA muscle,
      thigh muscle, and lumbosacral spinal cord. CNTFRalpha mRNA was abundantly
      expressed in the BC/LA and thigh around the time of birth; expression declined
      progressively after birth and remained low into adulthood. In contrast,
      CNTFRalpha message remained high in the lumbosacral spinal cord throughout
      development. Androgen regulation of CNTFRalpha expression was examined in
      prenatal animals by administering the androgen receptor blocker hydroxyflutamide
      from embryonic days E18 through E21. Four days of androgen deprivation caused a
      significant up-regulation of CNTFRalpha mRNA in the BC/LA, thigh, and spinal cord
      of male fetuses. After castration in adulthood, CNTFRalpha expression in the
      BC/LA transiently increased, then decreased below control levels. Expression of
      CNTFRalpha in thigh muscles and the lumbosacral spinal cord was not affected by
      adult castration. Thus, the perineal muscles and motoneurons are potential sites
      of direct CNTF action, and expression of the CNTFRalpha gene is modulated by
      androgen, especially in the androgen-sensitive perineal muscles. Transient up
      regulation of CNTFRalpha following castration or androgen receptor blockade may
      represent a protective response designed to counteract the muscle atrophy
      normally induced by androgen withdrawal.

PMID- 9581977
TI  - Genes to Cells in Mishima.

PMID- 9581978
TI  - Interplay between positive and negative elongation factors: drawing a new view of
      DRB.
AB  - DRB is a classic inhibitor of transcription by RNA polymerase II (pol II).
      Although it has been demonstrated that DRB inhibits the elongation step of
      transcription, its mode of action has been elusive. DRB also markedly inhibits
      human immunodeficiency virus (HIV) transcription, by targeting the elongation
      which is enhanced by the HIV-encoded transactivator Tat. Two factors essential
      for DRB action have recently been identified. These factors, positive
      transcription elongation factor b (P-TEFb) and DRB sensitivity-inducing factor
      (DSIF), positively and negatively regulate pol II elongation, and are likely to
      be relevant to the function of Tat. In this review, we summarize the recent
      findings on these factors, and discuss a possible model for the molecular
      mechanism of DRB action.

PMID- 9581979
TI  - A measure of the mitotic index: studies of the abundance and half-life of p34cdc2
      in cultured cells and normal and neoplastic tissues.
AB  - BACKGROUND: The cdc2 gene encodes a protein kinase, p34cdc2, that is essential
      for mitosis, and is present at high levels in dividing cells. Classical studies
      of the levels of this protein in dividing and resting cells used antibodies that
      cross-react with other members of the CDK family, in particular with CDK2. We
      have therefore re-examined the abundance of p34cdc2 in a variety of tissues and
      cell lines, using a highly specific, epitope-mapped monoclonal antibody that does
      not react with CDK2. RESULTS: We observed high levels of p34cdc2 in proliferating
      cells, especially those in neoplastic tissues. Cells that have withdrawn from the
      cell cycle have low or undetectable levels. At the end of mitosis, the level of
      p34cdc2 declines, with simple first-order kinetics, with a half-life which is
      never less than 6h and is more typically about 18h. The persistence of p34cdc2
      after the last cell division is comparable to that of PCNA, a commonly used
      marker of proliferation. CONCLUSIONS: The immunochemical detection of p34cdc2
      provides an accurate, reliable and meaningful measure of the proliferative
      activity of cells in tissues. We suggest that p34cdc2 should be considered as the
      most authentic molecular marker of the mitotic index.

PMID- 9581980
TI  - Type I interferons are essential mediators of apoptotic death in virally infected
      cells.
AB  - BACKGROUND: The interferons (IFNs) have been extensively studied in the context
      of host defence against viral infection. In the established model of IFN action,
      virally infected cells secrete type I IFNs (IFN-alpha/beta) which induce an
      antiviral state in uninfected cells. However, it is not clear how IFNs function
      on the infected cells. It has been reported that cells infected by some viruses
      die by apoptosis. RESULTS: In the present study, we found that three types of
      viruses commonly induce apoptosis in primary cell cultures. Importantly, we
      observed that virus-induced apoptosis was inhibited by anti-IFN-alpha/beta
      antibodies, and in cells lacking either the type I IFN receptor 1 (IFNAR1) or its
      downstream mediator, Stat1 (Signal transducer and activator of transcription 1).
      IFN-alpha treatment by itself did not induce apoptosis unless it was combined
      with transfection by double-stranded RNA (dsRNA), which is normally generated
      during the course of viral infection. CONCLUSION: These results indicate a novel
      antiviral function of the type I IFNs, i.e. the selective induction of apoptosis
      in virally infected cells. In effect, these IFNs have a bifunctional role in
      limiting the spread of virus; eliciting an antiviral state in uninfected cells
      while promoting apoptosis in infected cells. Our results may help explain why
      IFNs are sometimes useful in the treatment of viral diseases and will provide
      further insight into the mechanisms of virus-induced pathogenesis.

PMID- 9581982
TI  - Region-specific expression of murine Hox genes implies the Hox code-mediated
      patterning of the digestive tract.
AB  - BACKGROUND: Hox genes encode transcription factors which are involved in the
      establishment of regional identities along the anteroposterior (AP) body axis. To
      elucidate the AP patterning of the digestive tract, we have systematically
      examined the expression patterns of Hox genes belonging to paralogue groups 6, 7,
      8 and 9 by whole-mount in situ hybridization and by section in situ hybridization
      analyses. RESULTS: The expression patterns of these genes showed co-linearity
      along the wall of the digestive tract, thereby yielding the Hox code of the gut.
      The expression boundaries of the Hox genes at later stages (12.5 d.p.c.)
      corresponded to the morphological boundaries of individual gut subdomains.
      CONCLUSIONS: The visceral mesoderm-restricted expression suggested that the Hox
      code primarily functions in the mesenchymal specification which eventually leads
      to the regional differentiation of gut subdomains as the result of epithelial
      mesenchymal interactions. Overlapping expression patterns were found among the
      paralogous Hox genes, indicating that the paralogues may have redundant functions
      in the specification of the gut.

PMID- 9581981
TI  - Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast
      cells.
AB  - BACKGROUND: While mast cells have been previously shown to express both GATA-1
      and GATA-2 mRNAs, individual functions for these related factors during their
      course of differentiation within the mast cell lineage have not yet been defined.
      To address this question, the expression of GATA-1 and GATA-2 mRNAs and proteins
      were examined in three mouse mast cell progenitor lines as well as in mast cells
      isolated from both wild-type and GATA-1-deficient mice. RESULTS: Both mast cell
      progenitor lines, as well as primary mouse bone marrow-derived mast cells (BMMCs)
      and peritoneal mast cells (PMCs) were examined by RNA blotting and immunological
      analyses. GATA-2 protein was abundantly expressed in all three mast cell lines
      and in BMMCs, but only weakly in some of PMCs. In contrast, GATA-1 protein was
      expressed in PMCs and BMMCs after culture in the presence of IL3 and SCF. We also
      found the presence of Alcian blue staining-positive but berberine staining
      negative mast cells in the skin of mice heterozygous to GATA-1 knock-down allele.
      CONCLUSION: These results suggest that the expression of GATA factor-dependent
      genes is regulated by GATA-2 during mast cell development and that GATA-1 is
      required for the specification of differentiated mast cell phenotypes.

PMID- 9581983
TI  - Caroli's disease.
AB  - Caroli's disease is characterized by multifocal segmental dilatation of the
      intrahepatic bile ducts. It is a rare congenital condition, which appears to be
      autosomal recessively inherited in most cases. There are two forms of disease,
      one associated with congenital hepatic fibrosis and a simple form occurring
      alone. Recent reports suggest that the simple form may be as common as that with
      congenital hepatic fibrosis. Other conditions, including choledochal cyst and
      renal cystic disease, are frequently associated. The major clinical feature is
      recurrent cholangitis, which may be complicated by intrahepatic calculi and
      hepatic abscess formation. There is good evidence that malignancy complicates
      Caroli's disease in approximately 7% of cases. The diagnosis rests on
      demonstrating that the cystic liver lesions are in continuity with the biliary
      tree. Modern imaging techniques allow the diagnosis to be made more easily and
      without invasive imaging of the biliary tree. The treatment depends on the
      clinical features and the location of the biliary abnormality. When the disease
      is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to
      remove the risk of malignancy. In diffuse Caroli's disease, treatment options
      include conservative or endoscopic therapy, internal biliary bypass procedures
      and liver transplantation in carefully selected cases.

PMID- 9581984
TI  - Caroli's disease: 1977-1995 experiences.
AB  - OBJECTIVE: Until recently, congenital cystic dilatation of the intrahepatic
      biliary ducts (Caroli's disease) has been recognized infrequently. This report
      aimed to analyse and discuss our observations on 21 adult patients with the
      disease. PATIENTS: From 1977 to 1995, 21 patients (eight women and 13 men), aged
      17 to 68 years, were diagnosed and treated for Caroli's disease at Yuksek Ihtisas
      Hospital. The mean duration of the disease was 6.5 years. RESULTS: The commonest
      presenting symptom was abdominal pain, a feature in 18 cases. The distribution of
      the biliary lesions was bilobar in 12 patients and monolobar in nine. Two of them
      were congenital hepatic fibrosis. Twenty-one patients had coexisting
      hepatobiliary disease, associated with Caroli's disease. Approximately 95% of our
      patients had cystolithiasis, cholelithiasis or both. Surgical treatment was used
      in 18 patients, a partial hepatectomy being carried out in seven of them, an
      internal biliary drainage by choledocystojejunostomy in five cases, and by
      choledochotomy in four cases. Three cases with Caroli's disease were treated with
      endoscopic sphincterotomy and stone extraction. In the follow-up period, four of
      our patients died. CONCLUSION: Caroli's disease is being diagnosed more
      frequently as a result of improved diagnostic capabilities. The aim of the
      treatment is to obtain sufficient biliary drainage and to relieve the symptoms.

PMID- 9581985
TI  - Is coffee a colonic stimulant?
AB  - BACKGROUND: It is unclear if ingestion of coffee affects colonic function and if
      this effect is due to its caffeine content. We investigated the effects of coffee
      on colonic motor activity in healthy humans. METHODS: We performed ambulatory
      colonic manometry by placing a six-sensor solid-state probe up to the mid
      transverse colon in 12 healthy subjects. The following day, over a 10 h period,
      subjects received four stimuli: 240 ml of three drinks at 45 degrees C in random
      order: black Colombian coffee (150 mg caffeine), decaffeinated coffee or water
      and 1000 kcal meal. We analyzed the effects of each stimulant on colonic motor
      responses. RESULTS: Caffeinated coffee, decaffeinated coffee and meal induced
      more activity in the colon with a greater area under the curve of pressure waves
      (P < 0.01) and a greater number of propagated contractions (P < 0.05) when
      compared with water. Caffeinated coffee, decaffeinated coffee and meal induced
      greater (P < 0.05) motor activity in the transverse/descending colon when
      compared with the rectosigmoid colon. The effects of decaffeinated coffee on
      colonic motility were not significantly different from those of water or
      caffeinated coffee and were lower (P < 0.05) than that of a meal. CONCLUSION:
      Caffeinated coffee stimulates colonic motor activity. Its magnitude is similar to
      a meal, 60% stronger than water and 23% stronger than decaffeinated coffee.

PMID- 9581986
TI  - Gastro-oesophageal reflux disease in primary care: an international study of
      different treatment strategies with omeprazole. International GORD Study Group.
AB  - OBJECTIVE: To assess the efficacy of omeprazole in patients presenting with
      troublesome reflux symptoms. DESIGN: Randomized, double-blind, parallel-group,
      placebo-controlled comparison. SETTING: Primary care. SUBJECTS: Patients were
      recruited using a symptom-based questionnaire for diagnosis of gastro-oesophageal
      reflux disease. INTERVENTIONS: After endoscopy, patients without endoscopic
      oesophagitis were randomized to omeprazole 20 mg (Ome20), omeprazole 10 mg
      (Ome10) or placebo once daily for 4 weeks (n = 261) and those with oesophagitis
      (except circumferential/ulcerative) were randomized to receive either Ome20 or
      Ome10 once daily for 4 weeks (n = 277). Patients not symptom-free at 4 weeks
      received open treatment with Ome20 once daily for a further 4 weeks. Those
      symptom-free at 4-8 weeks were followed up for 6 months off treatment, to see
      whether their symptoms recurred. MAIN OUTCOME MEASURE: Complete upper GI symptom
      relief during week 4 on Ome20 or Ome10 in patients with or without endoscopic
      oesophagitis. RESULTS: Forty one percent of all patients on Ome20 and 35% on
      Ome10 reported complete relief from upper GI symptoms during week 4, whilst 73%
      of the patients on Ome20 and 62% on Ome10 obtained sufficient control. Complete
      relief during week 4 was reported by 19% of endoscopy-negative patients on
      placebo, and sufficient control by 35%. Endoscopic healing at 4 weeks occurred in
      76% of oesophagitis patients on Ome20 and in 56% on Ome10. After 6 months off
      treatment, 90% of patients with oesophagitis and 75% of endoscopy-negative
      patients reported symptomatic relapse. CONCLUSION: Both 10 mg and 20 mg of
      omeprazole gave effective relief of symptoms, although 20 mg gave superior
      healing in patients with oesophagitis. After cessation of treatment, symptomatic
      relapse was rapid and frequent in both endoscopy-positive and endoscopy-negative
      patients.

PMID- 9581987
TI  - Effects of interferon therapy on fibrosis serum markers in HCV-positive chronic
      liver disease.
AB  - OBJECTIVE: To evaluate serum levels of prolyl-hydroxylase and helical domain of
      Type IV collagen, markers of hepatic fibrogenesis, in patients with HCV-positive
      chronic liver disease and the effects of interferon therapy on these markers.
      DESIGN: Prolyl-hydroxylase and Type IV collagen were determined before therapy
      and each month during the treatment and follow-up. METHODS: Fifty-seven HCV
      positive patients were studied. All the subjects received alpha2a recombinant
      interferon, 6 MU subcutaneously three times a week for 4 weeks, followed by 3 MU
      thrice weekly for 5 months. After cessation of treatment, each patient was
      followed for 12 months. Prolyl-hydroxylase and helical domain of Type IV collagen
      were measured by using immunoenzymatic methods. HCV-RNA and HCV genotype were
      determined according to the method of Okamoto. RESULTS: In the patients prolyl
      hydroxylase (39.8+/-8.9 ng/ml) was not different from controls (39.1+/-5.9
      ng/ml). On the contrary, the patients showed a mean Type IV collagen (133.6+/
      93.3 ng/ml) significantly (P < 0.01) higher than controls (100.2+/-10.5 ng/ml). A
      good relationship between the degree of liver fibrosis and the Type IV collagen
      serum level was found (r = 0.68; P < 0.005). In both responders and non
      responders the Type IV collagen levels decreased during interferon therapy.
      During the follow-up, in responders the Type IV collagen did not show
      modifications, while in non-responders/relapsers it returned rapidly to the
      pretreatment levels (139.1+/-100.7 ng/ml). CONCLUSION: In HCV-positive chronic
      liver disease, prolylhydroxylase is not a good marker of hepatic fibrosis, while
      Type IV collagen is a useful tool for evaluating fibrogenic activity. Interferon
      seems to be able to reduce the liver fibrosis even without the inhibition of
      viral replication and independently from liver necrosis.

PMID- 9581988
TI  - Evaluation of a new Near Patient Test for the detection of Helicobacter pylori.
AB  - OBJECTIVE: Peptic ulcer disease is rare in the absence of Helicobacter pylori.
      Testing for H. pylori has recently become easier with the development of Near
      Patient Tests. However, the validity of many of these tests is unknown. The aim
      of this study was to assess the validity of the QuickVue one-step Near Patient
      Test for H. pylori in a group of patients attending for endoscopy at a tertiary
      referral hospital. METHODS: In a retrospective study the QuickVue one-step serum
      test (Quidel) was performed on the stored serum from 193 patients whose H. pylori
      status had been determined by a 'gold standard' using urease testing, histology,
      culture and 14C-urea breath testing. Twenty four other patients presenting to
      endoscopy were studied prospectively. For these patients QuickVue was performed
      on capillary and venous samples and the results were compared to a similar 'gold
      standard'. Enzyme immunoassay (Premier, H. pylori, Meridian Diagnostics, OH, USA)
      was used to define H. pylori status of patients with indeterminate H. pylori
      status by the above criteria. RESULTS: In the retrospective study the QuickVue
      one-step H. pylori test had a sensitivity (CI) of 82% (75-89) and specificity of
      83% (74-92). In the prospective study on capillary blood its sensitivity (CI) was
      89% (52-100) and its specificity 93% (68-100); and on venous blood, 78% (40-97)
      and 93% (68-100). Premier has previously been shown to have a sensitivity and
      specificity of 100%. CONCLUSION: In this group of patients the QuickVue one-step
      H. pylori Near Patient Test was less accurate than the Premier ELISA test, but
      its ease of use and availability in primary care make it useful for patient
      screening.

PMID- 9581989
TI  - Screening for osteoporosis in Crohn's disease. A detailed evaluation of calcaneal
      ultrasound.
AB  - OBJECTIVES: To compare calcaneal broadband ultrasonic attenuation (BUA) and
      velocity of sound (VOS) in patients with Crohn's disease with an age-matched
      control population. The validity of BUA as a screening tool for osteoporosis was
      evaluated and the relationship between BUA and previous fracture studied. DESIGN:
      Cross-sectional study. BACKGROUND: Since patients with Crohn's disease are at
      risk of osteoporosis and premature fracture, routine assessment of bone mineral
      density (BMD) is recommended. Quantitative ultrasound of the calcaneum is an
      inexpensive and radiation-free means of assessing bone density which also
      provides information on bone microstructure. METHODS: BUA (dB/MHz) and VOS (m/s)
      were measured at the calcaneum (CUBAclinical, McCue Ultrasonics, Winchester, UK)
      and compared with bone mineral density at the hip and lumbar spine measured by
      dual-energy X-ray absorptiometry (DEXA); 100 patients (42 men) with Crohn's
      disease and 52 age-matched healthy controls (23 men) were studied. RESULTS: BUA
      was significantly reduced in patients with Crohn's disease compared with age
      matched controls [76.53 dB/MHz (+/-17.3) vs 87.29 dB/MHz (+/-17.9), difference in
      means = 10.76, 95% CI -16.67, -4.85, P = 0.0004] and was significantly associated
      with BMD at the spine (r = 0.49, 95% CI 0.32, 0.63, P< 0.0001) and femoral neck
      (r = 0.54, 95% CI 0.38, 0.67, P < 0.0001). In the diagnosis of osteoporosis (t
      score <-2.5) BUA had a sensitivity of 66.7% at the femoral neck, with a
      specificity of 85.6%; sensitivity of BUA at the spine was 75% with specificity
      89%. CONCLUSION: Patients with Crohn's disease have reduced BUA compared with an
      age-matched control population. Calcaneal BUA is significantly associated with
      BMD at the hip and spine but the correlation is insufficient to recommend
      ultrasound as a screening tool for DEXA.

PMID- 9581990
TI  - A 5-year follow-up of self-expanding metal stents in the endoscopic management of
      patients with benign bile duct strictures.
AB  - BACKGROUND: Metal stents offer superior biliary drainage in patients with
      malignant bile duct obstruction, with fewer episodes of stent occlusion compared
      with polyethylene stents. Metal stent patency has only been studied over limited
      time periods in such patients with malignant disease. OBJECTIVE: To assess the
      long-term patency of metal stents in a group of patients with benign bile duct
      strictures who are suitable for extended follow-up. METHODS: Between May 1989 and
      May 1992, eight patients (median age 59.0 years; range 26-88 years) with benign
      biliary strictures were selected at a tertiary referral centre for insertion of a
      metal stent. Strictures were secondary to bile duct trauma (n = 5), chronic
      pancreatitis (n = 2) or idiopathic (n = 1). A long metal stent was inserted in
      three patients and a short metal stent in five patients. RESULTS: After a median
      follow-up of 64.5 months (range 26-81 months, seven of the eight patients are
      alive. Baby scope examination at 1 year showed complete epithelialization of the
      metal stent in all subjects examined. Median stent patency was 35 months (range 7
      72 months). Symptomatic episodes of metal stent occlusion have occurred on nine
      occasions in five patients (62.5%) secondary to mucosal hypertrophy (n = 3) or
      biliary calculi (n = 2). CONCLUSION: The long-term management of selected
      patients with benign bile duct strictures may be significantly improved by the
      use of metal stents avoiding the need for frequent polyethylene stent changes.

PMID- 9581991
TI  - Idiopathic megacolon associated with oesophageal achalasia.
AB  - We report a rare case of achalasia coexistent with megacolon. The patient, a 25
      year-old woman, presented at our hospital with a history of abdominal pain with
      distension, and was finally operated on for a megacolon. Five months later she
      presented symptoms of progressive dysphagia and heartburn. Oesophageal manometry
      of the upper and lower oesophageal sphincter and X-ray studies showed images
      compatible with achalasia. Oesophagomyotomy of the oesophagogastric junction
      (Heller procedure with Dor haemifundoplication technique) was performed. In the
      specimens taken for biopsy, neither pathology of the myenteric plexuses, nor
      atrophy of the muscle fibres was evident. Chagas' disease serological diagnosis
      for Trypanosoma cruzii, neurological disease, diabetes and all the pathological
      events related with neuromuscular disorders of the gastrointestinal tract proved
      negative. We believe that the pathological findings are related to a dysfunction
      of the physiological mediators of the upper and lower digestive tract motility.
      The present case is extraordinary and, to our knowledge, extremely rare. The
      association of the two pathological diseases is questionable, and the literature
      is reviewed.

PMID- 9581992
TI  - Prophylactic endoscopic ligation of high-risk oesophageal varices in a cirrhotic
      patient with severe haemophilia A.
AB  - One of the main complications in cirrhosis is haemorrhage from oesophageal
      varices. It is serious and often fatal, especially in cirrhotic patients with
      haemophilia. We describe the use of endoscopic variceal ligation (EVL) for
      prophylaxis of oesophageal variceal bleeding in a high-risk patient, a 40-year
      old Japanese man, with severe haemophilia A and liver cirrhosis caused by
      hepatitis C virus. He had large, coil-shaped varices with a red colour sign,
      predicting the likelihood of haemorrhage. Administration of omeprazole and factor
      VIII concentrate achieved rapid healing of the post-EVL ulcers and prevented
      bleeding from them. Four EVL sessions eradicated oesophageal varices completely,
      and he has had no recurrence of varices for 2 years, indicating that the
      procedure was of considerable benefit.

PMID- 9581993
TI  - Autoimmune chronic active hepatitis associated with the presence of
      antiphospholipid antibodies.
AB  - We report a patient with clinical, biochemical and immunological indices
      suggestive of autoimmune hepatitis with marked transaminasaemia, raised
      immunoglobulins and positive anti-nuclear and anti-smooth muscle antibodies. A
      coagulation screen revealed a transient, markedly increased, activated, partial
      thromboplastin time and a normal prothrombin time, with elevated levels of
      anticardiolipin antibodies and the presence of lupus anticoagulant, indicating
      the presence of antiphospholipid antibodies. Subsequent histology confirmed
      moderate hepatitis with piecemeal necrosis and fibrosis. Appropriate autoimmune
      therapy was commenced. This presentation illustrates the rare association of anti
      phospholipid antibodies with autoimmune chronic active hepatitis presenting with
      a temporarily abnormal coagulation screen.

PMID- 9581995
TI  - Late-onset idiopathic hypoparathyroidism as a cause of diarrhoea.
AB  - A 62-year-old man presented with a 20-month history of intermittent watery
      diarrhoea and hypocalcaemia. At age 43 he had undergone partial gastrectomy with
      Billroth II anastomosis for perforated peptic ulcer and at age 57 developed
      megaloblastic anaemia with low serum cobalamin and folate levels. Exhaustive
      gastrointestinal studies performed to ascertain the cause of the diarrhoea were
      all negative. Plasma parathyroid hormone levels were undetectable and late-onset
      idiopathic hypoparathyroidism was diagnosed. Normalization of hypocalcaemia
      promptly corrected the bowel habit. Idiopathic hypoparathyroidism is an unusual
      cause of diarrhoea that should, however, be considered in patients with
      hypocalcaemia and associated diarrhoea without evidence of primary intestinal
      disease.

PMID- 9581994
TI  - Upper gastrointestinal bleeding due to a malignant Schwannoma of the stomach.
AB  - A case history of a patient showing signs of upper gastrointestinal bleeding is
      described. Extensive analysis showed that the bleeding was due to a malignant
      Schwannoma of the stomach with several lymph node metastases. The patient was
      operated on and is doing well 5 years after surgery. The literature on this rare
      malignant tumour is reviewed.

PMID- 9581996
TI  - Metastatic transitional cell carcinoma presenting as diffuse liver disease.
AB  - Three cases of transitional cell carcinoma (TCC) metastatic to the liver are
      reported. Each case presented as diffuse liver disease. This is a rare
      presentation, most liver metastases occurring as an isolated mass or multiple
      discrete masses.

PMID- 9581997
TI  - Health of the nation: the emergence of the Western diseases and their possible
      control.

PMID- 9581999
TI  - A survey from the literature of plants used to treat scorpion stings.
AB  - A catalogue of plants used to treat envenomation by scorpions has been compiled
      from a comprehensive range of over 30 reference books and review papers. Details
      of the parts used and the method of use are given, as well as the geographical
      source. The possible pharmacological and chemical basis of the use of some of the
      plants listed is discussed and compared with plants used to treat envenomation by
      snakes.

PMID- 9581998
TI  - Hepatitis A: insights into new trends in epidemiology.

PMID- 9582000
TI  - Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and
      antioxidants activity in vitro.
AB  - The effects on toxic and behavioral levels of guarana (Paullinia cupana) were
      assessed in rats and mice subsequent to acute and chronic administrations and
      were compared to those produced by Ginseng (Panax ginseng). Experimental
      parameters included tests for antioxidant capacity in vitro and measured in vivo,
      toxicological screening, progress in weight, motor activity, death rate, and
      histopathological examination of the viscera. Guarana showed an antioxidant
      effect because, even at low concentrations (1.2 microg/ml), it inhibited the
      process of lipid peroxidation. In high doses of 1000-2000 mg/kg (i.p. and p.o.)
      it did not induce significant alterations in parameters for toxicological
      screening. No effects on motor activity were observed, neither did guarana alter
      the hypnotic effect of pentobarbital. Ginseng (250-1000 mg/kg i.p.), however,
      elicited reductions in motor activity, eyelid ptosis and bristling fur.
      Consumption of liquids containing guarana or ginseng and progress in weight of
      the animals remained at levels similar to the controls, even after prolonged
      administration. The percentage mortality was equivalent in control and in treated
      groups. The absence of toxicity of guarana was also demonstrated by
      histopathological examination, with no alteration being detected in heart, lungs,
      stomach, small and large intestine, liver, pancreas, kidneys, bladder and spleen.

PMID- 9582001
TI  - Anti-nociceptive and anti-inflammatory effects of some Jordanian medicinal plant
      extracts.
AB  - The anti-nociceptive effect of ethanolic extract of 11 traditionally used
      Jordanian plants was studied by using the acetic acid-induced writhing and hot
      plate test in mice. The anti-inflammatory effect of these plants was determined
      by xylene-induced ear oedema in mice and cotton pellet granuloma test in rats.
      Mentha piperita, Cinnamomum zeylanicum, Apium graveolens, Eucalyptus
      camaldulentis, and Ruta graveolens possess an anti-nociceptive effect against
      both acetic acid-induced writhing and hot plate-induced thermal stimulation. M.
      piperita, Jasminum officinale, Commiphora molmol, and Beta vulgaris possess an
      anti-inflammatory effect against acute (xylene-induced ear oedema) and chronic
      (cotton-pellet granuloma) inflammation. The anti-nociceptive and anti
      inflammatory effects were dose dependent. These data affirm the traditional use
      of some of these plants for painful and inflammatory conditions.

PMID- 9582002
TI  - Effect of Syzygium aromaticum extract on immediate hypersensitivity in rats.
AB  - We investigated the effect of aqueous extract of Syzygium aromaticum (L.) Merr.
      et Perry (Myrtaceae) flower bud (SAFB) on immediate hypersensitivity. SAFB
      inhibited compound 48/80-induced systemic anaphylaxis in rats (IC50 = 31.25
      mg/kg, i.p.). SAFB also inhibited local immunoglobulin E (IgE)-mediated passive
      cutaneous anaphylactic reaction (IC50 = 17.78 mg/kg, i.v.; IC50 = 19.81 mg/kg,
      p.o.). When SAFB was pretreated at concentrations ranging from 25 to 1000 mg/kg,
      the serum histamine levels were reduced in a dose-dependent manner. Moreover,
      SAFB dose-dependently inhibited histamine release from rat peritoneal mast cells
      (RPMC) by compound 48/80 or anti-dinitrophenyl IgE. When SAFB was added, the
      level of cAMP in RPMC transiently and significantly increased about 47-fold at 10
      s compared with that of basal cells. These results indicate that SAFB inhibits
      immediate hypersensitivity by inhibition of histamine release from mast cells in
      vivo and in vitro.

PMID- 9582003
TI  - Endothelium-dependent vasorelaxing activity of aqueous extracts of Ilex
      paraguariensis on mesenteric arterial bed of rats.
AB  - The effects of aqueous extracts of Ilex paraguariensis leaves (AEIp) were
      studied. Mesenteric arterial bed (MAB), precontracted by methoxamine with or
      without intact endothelium, was mounted on a tissue bath and exposed to plant
      extracts (bolus). The bolus injections of AEIp (300-1050 microg) significantly
      inhibited, in a concentration-dependent manner, the maximal contractile response
      induced by methoxamine (30 microm) in MAB. The endothelium-dependent relaxations
      were reversed by N(G)-nitro-L-arginine methyl ester (10 mM), whereas methylene
      blue (100 microM) was not capable of effectively inhibiting the AEIp-induced
      vasodilatation of MAB. The vasorelaxing effect of AEIp persisted in the presence
      of indomethacin (10 microM). These results suggest the involvement of NO of
      endothelial source (or others factors) in this vasodilatory effect.

PMID- 9582004
TI  - Inhibition of cytochrome P450-dependent monooxygenases by an alkaloid fraction
      from Helietta apiculata markedly potentiate the hypnotic action of pentobarbital.
AB  - Crude alkaloid fraction (CAF) isolated from the leaves of Helietta apiculata
      showed the presence of furoquinolines. The extract was investigated to determine
      if it can enhance the sensitivity of the central nervous system (CNS) to the
      hypnotic action of pentobarbital. Administration of CAF to mice in a dose range
      of 300-500 mg/kg prior to an injection of pentobarbital (40 mg/kg, i.p.) was
      associated with a statistically significant decrease of sleep latency and
      prolongation of pentobarbital-induced sleeping time. Pretreatment of rats with
      the same alkaloid extract (150 mg/kg, i.p. for 4 days) prior to administration of
      pentobarbital (40 mg/kg, i.p.) caused not only significant reduction of the
      levels of microsomal proteins, total cytochrome P450 enzymes and a decrease of
      aminopyrin-N-demethylation and 3,4-benz(a)pyrene hydroxylation but also changed
      the pattern of cytochrome P450. It is concluded that the CAF isolated from H.
      apiculata can potentiate the CNS depressant effect of pentobarbital due to
      alteration of barbiturate metabolism through inhibition, mainly, of cytochrome
      P450-dependent enzymes.

PMID- 9582005
TI  - Effects of leaf extract of Caesalpinia bonduc (Caesalpiniaceae) on the
      contractile activity of uterine smooth muscle of pregnant rats.
AB  - The calcium dependency and the cholinergic effect of the leaf extract of
      Caesalpinia bonduc Roxb. (Caesalpiniaceae) was studied in isolated pregnant rat
      myometrium preparations. Isometric contractions were recorded. The extract (Cebo)
      increased the contractile force in the isolated strips in a concentration
      dependent manner. The effects were comparable to those obtained with
      acetylcholine. Contractions induced by Cebo or acetylcholine were inhibited in
      the presence of atropine. The stimulating action of Cebo on the contractile
      responses of isolated myometrium preparations inhibited by atropine may be
      mediated by cholinergic receptors. In calcium-free solution Cebo induced a tonic
      contraction (contracture) of the muscle. Moreover, in high-potassium calcium-free
      solution Cebo caused contracture of the uterine smooth muscle. Cebo was still
      able to elicit contractions in calcium-free solution containing EDTA or EGTA.
      These findings suggest the existence of cholinergic receptors sensitive to Cebo
      which could influence the influx of calcium (phasic contraction) and mobilization
      of calcium from cellular stores (tonic contraction), both of which are
      responsible for the increase of contractile activity and development of the
      contracture of uterine smooth muscle.

PMID- 9582006
TI  - Heterotheca inuloides: anti-inflammatory and analgesic effect.
AB  - Heterotheca inuloides Cass. (Asteraceae) is used in the traditional medicine of
      Mexico. The aqueous extract obtained from the flowers of H. inuloides was
      assessed for anti-inflammatory activity by carrageenan-induced edema test. At 100
      mg/kg, i.p, it produced 29% inhibition of inflammation. Ethyl ether (HI-1),
      butanol (HI-2) and aqueous fraction (HI-3) were obtained from the aqueous
      extract. The biological assay, by carrageenan-induced edema test, gave the
      following values (% inhibition): HI-1, 19.9; HI-2, 58.0 and HI-3, 30.0. HI-2 was
      significantly more effective than HI-1 and HI-3. The dose-effect curve of HI-2
      was obtained and the calculated ED50 was 29.7 (22.5-39.2) mg/kg. The peritoneal
      examination after the treatment with HI-2 showed that the anti-inflammatory
      action of H. inuloides was not due to an irritating effect at the injection site.
      At 50-100 mg/kg, i.p., HI-2 inhibited inflammation induced by dextran (38.9-68.1%
      inhibition) and arachidonic acid (0-33.9%). No effect was observed at the same
      doses for zymosan or C16-paf-induced edema. In addition, HI-2 reduced abdominal
      constrictions in mice following injection of acetic acid: at 50-100 mg/kg, it
      gave 73.8-78.2% inhibition. The ulcerogenic assay showed that ulcer indices after
      HI-2 i.p. treatment were 0.5 +/- 0.5 at 50 mg/kg and 1.2 +/- 0.4 at 100 mg/kg.
      The results showed related anti-inflammatory activity and the analgesic effect of
      HI-2.

PMID- 9582007
TI  - Screening of Australian medicinal plants for antiviral activity.
AB  - Extracts of 40 different plant species used in the traditional medicine of the
      Australian Aboriginal people have been investigated for antiviral activity. The
      extracts have been tested for activity against one DNA virus, human
      cytomegalovirus (HCMV) and two RNA viruses, Ross River virus (RRV) and poliovirus
      type 1, at non-cytotoxic concentrations. The most active extracts were the aerial
      parts of Pterocaulon sphacelatum (Asteraceae) and roots of Dianella longifolia
      var. grandis (Liliaceae), which inhibited poliovirus at concentrations of 52 and
      250 microg/ml, respectively. The extracts of Euphorbia australis (Euphorbiaceae)
      and Scaevola spinescens (Goodeniaceae) were the most active against HCMV.
      Extracts of Eremophila latrobei subsp. glabra (Myoporaceae) and Pittosporum
      phylliraeoides var. microcarpa (Pittosporaceae) exhibited antiviral activity
      against RRV.

PMID- 9582008
TI  - Effect of ashwagandha on lipid peroxidation in stress-induced animals.
AB  - The aqueous suspension of root extract of an Indian drug ashwagandha (Withania
      somnifera L. (Solanaceae)) was evaluated for its effect on lipid peroxidation
      (LPO) in stress-induced animals. Elevation of LPO was observed in rabbits and
      mice after intravenous administration of 0.2 microg/kg of lipopolysaccharide
      (LPS: from Klebsiella pneumoniae) and 100 microg/kg of peptidoglycan (PGN: from
      Staphylococcus aureus), respectively. The peak was reached immediately after PGN
      and 2-6 h after LPS administration. Simultaneous oral administration of
      ashwagandha (100 mg/kg) prevented the rise in LPO in rabbits and mice.

PMID- 9582009
TI  - Effects of leaf aqueous extract of Bidens pilosa (Asteraceae) on KCl- and
      norepinephrine-induced contractions of rat aorta.
AB  - The effect of leaf aqueous extract of Bidens pilosa Linn. on KCl- and
      norepinephrine-induced contractions of rat aortic strips was studied. In aortic
      strips with endothelium intact, contractions induced using 60 mM KCl and 10(-5) M
      norepinephrine were dose-dependently relaxed by the extract, a more significant
      effect being seen with norepinephrine-induced contractions. Following mechanical
      damage to the aortic endothelium, inhibition of contractions was more prominent
      (105%) with the norepinephrine-induced contractions compared with KCl-induced
      contractions (15%) when the maximal dose (8 mg/ml) of the extract was used. The
      results suggest that the relaxation effect of the extract may be due to the
      blockade of the influx of extracellular Ca2+ into the cell.

PMID- 9582010
TI  - Piscicidal properties of piperovatine from Piper piscatorum (Piperaceae).
AB  - Extraction of the roots of the Amazonian medicinal plant, Piper piscatorum
      Trelease and Yuncker, with MeOH and subsequent bioassay guided fractionation
      using the guppy, Girardina guppii yielded the active amide, N-isobutyl-6-(p
      methoxyphenyl) 2E, 4E-hexadieneamide (piperovatine) and a second inactive amide,
      N-isobutyl-(E)-7-(3,4-methylenedioxyphenyl)hept-2-enamide (pipercallosidine). The
      former displayed an LC50 of 115 ng/ml in toxicity tests and proved to be the
      constituent responsible for the dual ethnobotanical uses of this plant: that of
      fish stupefacient (barbasco) and oral local anesthetic.

PMID- 9582011
TI  - Activation of protein kinase C delta by the c-Abl tyrosine kinase in response to
      ionizing radiation.
AB  - The c-Abl protein tyrosine kinase is activated by ionizing radiation (IR) and
      certain other DNA-damaging agents. The present studies demonstrate that c-Abl
      associates constitutively with protein kinase C delta (PKCdelta). The results
      show that the SH3 domain of c-Abl interacts directly with PKCdelta. c-Abl
      phosphorylates and activates PKCdelta in vitro. We also show that IR treatment of
      cells is associated with c-Abl-dependent phosphorylation of PKCdelta and
      translocation of PKCdelta to the nucleus. These findings support a functional
      interaction between c-Abl and PKCdelta in the cellular response to genotoxic
      stress.

PMID- 9582012
TI  - Association of PKC delta and active Src in PMA-treated MCF-7 human breast cancer
      cells.
AB  - Phorbol ester treatment of MCF-7 cells led to the tyrosine phosphorylation and
      activation of PKC delta. However, through Western blot analysis and in vitro
      immunecomplex kinase assays, we detected a differential localization of tyrosine
      phosphorylated PKC delta and catalytically active PKC delta. Catalytically active
      PKC delta was concentrated in Triton X-100 solubilized-membrane fractions while
      tyrosine-phosphorylated PKC delta was localized to the cytosol fraction. Phorbol
      ester treatment of MCF-7 cells stimulated both the time-dependent in vivo
      association of Src with PKC delta, evidenced in Src immunoprecipitates by the co
      immunoprecipitation of PKC delta, and activation of Src, evidenced in Src
      immunoprecipitates as an increase in reactivity with a Src antibody (clone 28)
      reactive only with active Src (dephosphorylated on residue 530) and in Src and
      PKC delta immunoprecipitates by an increase in Src kinase activity. While our
      data are consistent with reports in the literature showing the activator/stimulus
      dependent tyrosine phosphorylation of PKC delta, our data show that the tyrosine
      phosphorylation of PKC delta is not essential for kinase activity. These results
      are the first to demonstrate an in vivo association between PKC delta and active
      Src in the absence of over-expression of either PKC delta or Src, and support the
      association of Src and PKC delta towards a physiological function.

PMID- 9582013
TI  - Hyperphosphorylated p107 and p130 bind to T-antigen: identification of a critical
      regulatory sequence present in RB but not in p107/p130.
AB  - The retinoblastoma tumor suppressor RB and its related proteins, p107 and p130,
      are targets of several viral oncoproteins, including SV40 large T-antigen (T-Ag)
      and adenovirus E1A. T-Ag and E1A each contains an LXCXE-peptide motif through
      which binding to the conserved 'A/B pocket' present in RB, p107 and p130 is
      achieved. The LXCXE-binding activity of RB, we have previously shown, is
      inhibited by phosphorylation at Thr 821 and 826 in the C-terminal region of RB.
      Thr 821 and its surrounding sequence is unique to RB and not found in p107 or
      p130. Interestingly, hyperphosphorylation of p107 does not disrupt its ability to
      bind T-Ag or to inhibit the transactivating function of E1A. Insertion of a
      fourteen amino acid sequence of RB containing Thr 821 into p107 prevents binding
      of T-Ag and E1A to phosphorylated p107. These results show that the RB sequence
      surrounding Thr 821 plays a critical role in the regulation of the 'A/B pocket'
      function. In addition, these data indicate that the protein binding functions of
      RB and p107 are not equivalently regulated by phosphorylation.

PMID- 9582015
TI  - TP53 DNA contact mutations are selectively associated with allelic loss and have
      a strong clinical impact in head and neck cancer.
AB  - Recent studies have suggested that different mutation types within the core
      domain of the tumour suppressor protein p53, i.e. DNA contact mutations and
      structural mutations, confer different biological properties. We have analysed in
      86 head and neck squamous cell carcinomas (HNSCC), whether these p53 mutation
      types have a differential clinical impact. Thirty-seven missense mutations were
      identified. Thirteen of these (36%) were DNA contact mutations, occurring in the
      L3 loop, in the H2 loop sheet helix motif, in the S10 beta strand and in Zinc
      binding residues. Microsatellite marker analysis revealed a selective association
      between these mutations and the loss of wild-type alleles (100% LOH vs 50% LOH in
      tumours with structural mutations; P=0.0034, Fisher's exact, 2-tailed). In
      comparison to structural mutations or to the absence of mutations in the core
      domain, DNA contact mutations were associated with higher tumour stages (84.6% vs
      62%), a higher incidence of lymph node metastasis (91.7% vs 56%; P=0.014,
      Fisher's exact, 2-tailed), a shortened recurrence-free survival (8.1 months vs
      23.7 months, P=0.047, log rank test) and overall survival (11 months vs 29.2
      months; P=0.003, log rank test). The latter was also the case when only stage IV
      tumours were analysed (P=0.0055, log rank test). These data indicate that in
      HNSCC, TP53 DNA contact mutations confer a strong selection pressure to eliminate
      wild-type alleles, and that they result in an accelerated tumour progression and
      reduced therapeutic responsiveness.

PMID- 9582014
TI  - In B16 melanoma cells, the inhibition of melanogenesis by TPA results from PKC
      activation and diminution of microphthalmia binding to the M-box of the
      tyrosinase promoter.
AB  - In B16 melanoma cells, cAMP-induced melanogenesis is inhibited by the tumor
      promoting phorbol ester, TPA. However, the role of PKC activation or depletion in
      the inhibition of melanogenesis by TPA remains controversial. In this report,
      using specific PKC inhibitors, we demonstrated that PKC inhibition does not
      impair cAMP-induced melanin synthesis and tyrosinase expression. Further, the
      inhibition of melanogenesis by TPA results from a decrease of the tyrosinase
      promoter transcriptional activity and this effect is mimicked by over-expression
      of a constitutively active form of PKC alpha. These findings clearly demonstrate
      that PKC activation accounts for the inhibition of melanin synthesis by TPA.
      Additional experiments were undertaken to elucidate the mechanism by which TPA
      inhibits the tyrosinase gene transcription. Deletions and mutation in the
      tyrosinase promoter showed that TPA acts on a M-box which is involved in tissue
      specific expression and regulation by cAMP of the tyrosinase gene. We showed that
      TPA decreases the binding of microphthalmia, a basic helix-loop-helix
      transcription factor, to the M-box. Since microphthalmia, strongly stimulates the
      transcriptional activity of the promoter we propose that TPA, through PKC
      activation, decreases microphthalmia binding to the M-box of the tyrosinase
      promoter, thereby leading to a reduced tyrosinase expression and melanogenesis
      inhibition.

PMID- 9582016
TI  - Activation of the Xmrk proto-oncogene of Xiphophorus by overexpression and
      mutational alterations.
AB  - Xmrk is a receptor tyrosine kinase closely related to the human EGF receptor. In
      the teleost fish Xiphophorus two versions of the Xmrk gene exist, an oncogene
      (ONC) and a proto-oncogene (INV). While ONC-Xmrk is the melanoma-inducing gene,
      INV-Xmrk appears not to be involved in transformation of pigment cells. To
      elucidate the mechanism that converts the proto-oncogene into a transforming
      oncogene a comparative analysis of the structure, expression and function of both
      versions of the gene was performed. In contrast to ONC-Xmrk which is expressed at
      high levels in melanoma cells, the proto-oncogene INV-Xmrk is ubiquitously
      expressed at very low levels indicating overexpression as one possible reason for
      tumorigenicity by ONC-Xmrk. As sequence comparison of the proto-oncogene and the
      oncogene revealed a number of amino acid changes, a possible effect of these
      mutations on the activation of the ONC-Xmrk receptor was determined. A
      constitutive activation of the oncogenic receptor was found and ectopic
      expression of INV-Xmrk after microinjection into medakafish embryos did not lead
      to the high tumour rate in transgenic fish as observed for the oncogene. Our data
      therefore suggest that overexpression of the receptor alone is not sufficient for
      melanoma induction, but that in addition activating mutations in ONC-Xmrk are
      responsible for its full tumorigenic potential.

PMID- 9582018
TI  - Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an
      inverse manner.
AB  - Alternative splicing of cyclin D1 gene mRNA has recently been demonstrated. The
      novel transcript shows no splicing at the downstream exon 4 boundary and encodes
      a protein with an altered carboxyl-terminal domain that is a cyclin D1 variant;
      exon 5 is not included in the coding sequence which terminates downstream of exon
      4. We here produced cells that exogenously express each form of cyclin D1 and
      analysed their cell cycle regulation. We found that (1) alternative splicing
      forms of cyclin D1 modulated entry into the cell cycle in an inverse manner; (2)
      both splicing forms suppressed cell growth; and (3) cells overexpressing form [a]
      were inhibited from entry into and completion of the S phase, although form [b]
      expressing cells showed no reduction of G1- to S transition. We also found that
      overexpression of either cyclin D1 form upregulated Rb gene products, suggesting
      that this upregulation may be one of the causes of growth suppression in cyclin
      D1 overexpressing cells.

PMID- 9582017
TI  - Activation loop tyrosines contribute varying roles to TrkB autophosphorylation
      and signal transduction.
AB  - The TrkB receptor tyrosine kinase (RTK) is a high affinity receptor for the
      neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT
      4/5). Following exposure to BDNF or NT-4/5, TrkB is autophosphorylated on five
      cytoplasmic tyrosines: Y484, Y670, Y674, Y675, and Y785. Based on
      crystallographic analyses for others RTKs, TrkB tyrosines Y670, Y674, and Y675
      are expected to lie within a putative kinase activation loop. Phosphorylation of
      these activation loop tyrosines is postulated to be a conserved event required
      for complete RTK activation. Here, we have assessed the importance these
      activation loop tyrosines play in regulating TrkB autophosphorylation,
      cytoplasmic signal transduction, and cell proliferation. We show that while
      tyrosine 670 is dispensable for BDNF-inducible TrkB autophosphorylation and the
      activation of certain signal transduction events, it is required for complete
      TrkB-mediated cellular proliferation. Combinatorial mutagenesis of tyrosines 674
      and 675 only moderately affects TrkB autophosphorylation, but significantly
      impairs the BDNF-inducible stimulation of cytoplasmic signaling events and
      cellular proliferation. The combined mutation of all three activation loop
      tyrosines results in an inactive receptor, which is unable to autophosphorylate,
      stimulate signaling events, or induce mitogenesis. The data highlight the varying
      degrees of importance of the three activation loop tyrosines in TrkB mediated
      biological responses.

PMID- 9582019
TI  - BRCA1 physically associates with p53 and stimulates its transcriptional activity.
AB  - Mutations of the BRCA1 tumor suppressor gene are the most commonly detected
      alterations in familial breast and ovarian cancer. Although BRCA1 is required for
      normal mouse development, the molecular basis for its tumor suppressive function
      remains poorly understood. We show here that BRCA1 increases p53-dependent
      transcription from the p21WAF1/CIP1 and bax promoters. We also show that BRCA1
      and p53 proteins interact both in vitro and in vivo. The interacting regions map,
      in vitro, to aa 224-500 of BRCA1 and the C-terminal domain of p53. Tumor-derived
      transactivation-deficient BRCA1 mutants are defective in co-activation of p53
      dependent transcription and a truncation mutant of BRCA1 that retains the p53
      interacting region acts as a dominant inhibitor of p53-dependent transcription.
      BRCA1 and p53 cooperatively induce apoptosis of cancer cells. The results
      indicate that BRCA1 and p53 may coordinately regulate gene expression in their
      role as tumor suppressors.

PMID- 9582020
TI  - Expression of mouse telomerase reverse transcriptase during development,
      differentiation and proliferation.
AB  - We have identified the mouse telomerase reverse transcriptase component (mTERT)
      and demonstrate both substantial sequence homology to the human ortholog (hTERT),
      and the presence of reverse transcriptase and telomerase specific motifs.
      Furthermore, we show functional interchangeability with hTERT in in vitro
      telomerase reconstitution experiments, as mTERT produces strong telomerase
      activity in combination with the human telomerase RNA component hTR. The mouse
      TERT is widely expressed at low levels in adult tissues, with greatest abundance
      during embryogenesis and in adult thymus and intestine. The mTERT component mRNA
      levels were regulated during both differentiation and proliferation, while mTR
      levels remained constant throughout both processes. Comparison of mTERT and mTR
      levels to telomerase activity indicates that mTERT expression is more tightly
      linked to the regulation of telomerase activity during these processes than is
      mTR. In contrast to the situation in human cell cultures, mTERT transcript levels
      are present at readily detectable levels in primary cultured cells and are not
      upregulated following crisis. The widespread expression of mTERT in primary cells
      and mouse tissues could explain the increased frequency of spontaneous
      immortalization of mouse cells in culture and tumorigenesis in vivo.

PMID- 9582021
TI  - Activation of the cJun N-terminal kinase (JNK) pathway by the Epstein-Barr virus
      encoded latent membrane protein 1 (LMP1).
AB  - Expression of the oncogenic Epstein-Barr virus (EBV)-encoded Latent Membrane
      Protein 1 (LMP1) activates signalling on the NF-kappaB axis through two distinct
      domains in the cytoplasmic C-terminus of the protein, namely CTAR1 (aa 187-231)
      and CTAR2 (aa 351-386). Whilst this effect is responsible for some of the
      functional consequences of LMP1 expression, additional LMP1-mediated signalling
      pathways may exist which contribute to the pleiotropic activities of this
      protein. In this study we provide evidence of a kinase cascade being activated by
      LMP1. Thus, we demonstrate that stable or transient expression of the LMP1
      prototype from B95.8 in cells of epithelial or B cell origin activates the c-Jun
      N-terminal kinase (JNK, also known as the stress-activated protein kinase, SAPK)
      pathway, an effect which was found to be mediated through CTAR2 but not CTAR1.
      LMP1 from the Cao viral strain or LMP1 homologues from the simian EBV naturally
      infecting baboons and rhesus monkeys were also able to activate JNK. This
      phenomenon translates to induction of AP-1, a transcription factor which is
      readily activated by growth factors and mitogens. Interestingly, an LMP1/ CD40
      chimaera comprising of the N-terminus and transmembrane domain of LMP1 and the
      cytoplasmic tail of CD40 which shares a common TRAF binding motif with CTAR1,
      effectively induced JNK. As NF-kappaB and JNK are co-activated in LMP1-expressing
      cells, we investigated whether the two pathways are overlapping or independent.
      We have found that inhibition of NF-kappaB by metabolic inhibitors or a
      constitutively active mutated IkappaBalpha does not impair the ability of LMP1 to
      signal on the JNK axis. Conversely, whilst a dominant negative mutated SEK (JNKK)
      inhibited LMP1-induced JNK activation, it did not affect NF-kappa-B suggesting
      that these two LMP1-mediated pathways are divergent.

PMID- 9582022
TI  - Analysis of PTEN and the 10q23 region in primary prostate carcinomas.
AB  - Deletions involving chromosome 10q23 occur frequently in prostatic carcinomas.
      Recently, a novel tumour suppressor gene, PTEN, mapping to this interval, has
      been identified. Mutation or deletion of PTEN has been observed in a proportion
      of prostate cancer cell lines; however, primary prostate carcinomas have not been
      studied. We have investigated the involvement of PTEN in primary prostatic
      adenocarcinomas using a panel of 51 matched normal and prostate tumour DNAs. We
      first determined the proportion of tumours with allele loss at loci in 10q23
      which span the region containing the PTEN gene. Our results show that LOH
      involving 10q23 is common in primary prostate carcinomas. Twenty-five of 51 (49%)
      tumours showed loss of heterozygosity (LOH) over the region spanning the PTEN
      locus. We next directly analysed the PTEN gene for mutations of the coding region
      using single strand conformation polymorphism (SSCP) and sequence analyses. Of
      those tumours with LOH, only a single tumour was found to carry a missense
      mutation in PTEN. No mutations in PTEN were identified in tumours without LOH.
      Our results suggest either that mutation of PTEN is a late event in prostate
      tumorigenesis, or that another tumour suppressor gene important in prostate
      cancer may lie close to PTEN in 10q23.

PMID- 9582024
TI  - Defining the minimal requirements for papilloma viral E6-mediated inhibition of
      human p53 activity in fission yeast.
AB  - The majority of human anogenital carcinomas show evidence of papillomavirus
      infection. To facilitate viral replication, viruses disable key cellular
      responses which would otherwise precipitate cell suicide. An obligate factor in
      one such response is the p53 tumour suppressor protein. p53 gene mutation is an
      infrequent event in anogenital cancer, apparently due to the action of HPV E6
      protein, which inhibits wild-type p53 function by stimulating the degradation of
      p53 protein. p53 is required for the apoptotic response that is triggered in
      untransformed cells following inappropriate cell-cycling. E6 directed inhibition
      of p53 function thus facilitates the survival of transformed cells. We have
      developed a genetically tractable model that reports E6 protein-mediated human
      p53 inactivation in the fission yeast Schizosaccharomyces pombe. Functional
      dissection of the requirements for E6 directed inhibition in this system reveal
      an absolute requirement for the presence of both E6 protein and the human E3
      ubiquitin ligase, E6-AP. Using a defined set of E6 mutants we show that
      degradation of p53 protein rather than E6/p53 association is likely required for
      E6-mediated inhibition. This S. pombe based system represents a candidate screen
      for novel antiviral agents that act by disrupting the E6/E6-AP/p53 interaction.

PMID- 9582023
TI  - Src kinases and not JAKs activate STATs during IL-3 induced myeloid cell
      proliferation.
AB  - Interaction of IL-3 with its receptor is known to activate STAT-3 via
      phosphorylation of Tyrosine 701, which facilitates its dimerization and
      translocation to the nucleus, leading to the transcription of its target genes.
      In this communication, we have investigated the nature of tyrosine kinases that
      mediate STAT-3 phosphorylation during IL-3-mediated activation of myeloid cell
      proliferation. Our results show that interaction of IL-3 with its receptor leads
      to the activation of c-Src kinase activity, which in turn facilitates the binding
      of c-Src to STAT-3. This association leads to the phosphorylation of STAT-3,
      allowing this transcription factor to translocate to the nucleus. Expression of a
      dominant negative mutant of src (AMSrc) in these cells results in a block to IL-3
      mediated phosphorylation of STAT-3, and its ability to bind to DNA. On the other
      hand, expression of a dominant negative mutant of JAK2 (JAK2KE) had no effect on
      IL-3-mediated activation of STAT-3. Our results also show that AMSrc does not
      affect the phosphorylation of JAK2, suggesting that JAK and STAT phosphorylation
      events are mediated by two independent pathways. Inhibition of c-Src activation
      by AMSrc, which leads to a block to STAT-3 activation, results in a dramatic
      inhibition of cell proliferation mediated by IL-3. However, expression of AMSrc
      does not activate apoptotic pathways. In contrast, expression of JAK2KE results
      in accelerated apoptosis of 32Dcl3 cells grown in the absence of IL-3 with
      concomitant down-regulation of Erk-2 kinase activity. These results suggest that
      Src family kinases mediate the phosphorylation of STATs and play a critical role
      in signal transduction pathways associated with myeloid cell proliferation while
      JAK kinases mediate the activation of Erk-2 pathway which appears to provide
      antiapoptotic signals. Thus the activation of JAKs and STATs appear to be two
      independent but related events, which dictate two separate biological outcomes,
      the combination of which results in proliferation and survival of myeloid
      precursor cells.

PMID- 9582025
TI  - An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta subunit
      and HUMORF8, a putative deubiquitinating enzyme.
AB  - Peripheral blood cell DNA from a patient with a chronic myeloproliferative
      disorder was tested in the tumorigenicity assay. Upon tumor induction in nude
      mice we isolated a human oncogene by means of genomic cloning, exon trap analysis
      and cDNA cloning. Sequence analysis revealed a fusion product of the p85beta
      subunit of phosphatidylinositol (PI) 3-kinase and HUMORF8, a putative
      deubiquitinating enzyme, which has been generated during the DNA transfection
      process. Application of the tumorigenicity assay to various p85beta and HUMORF8
      cDNA constructs indicated that the recombination of both genes rather than the
      truncation of one of the fusion partners renders the chimeric protein
      tumorigenic. Moreover, sequence analysis of human wildtype p85beta revealed an
      alanine for serine substitution at a site important for the regulation of the
      lipid kinase activity of PI 3-kinase in human p85alpha. This variation may relate
      to differences in the mode of signal transduction from both p85 isoforms.

PMID- 9582026
TI  - A piece of my mind. Identity matters (or does it?).

PMID- 9582028
TI  - Future physicians care about patients--and changing economic patterns of care.

PMID- 9582027
TI  - Reports at European Urology Congress reflect issues of interest to aging men.

PMID- 9582029
TI  - Psychiatrists, journalists hold their first meeting of minds.

PMID- 9582030
TI  - From the Food and Drug Administration.

PMID- 9582031
TI  - From the Centers for Disease Control and Prevention. Demographic characteristics
      of persons without a regular source of medical care--selected states, 1995.

PMID- 9582032
TI  - From the Centers for Disease Control and Prevention. Outbreak of Campylobacter
      enteritis associated with cross-contamination of food--Oklahoma, 1996.

PMID- 9582033
TI  - Antiretroviral therapy for HIV infection: promises and problems.

PMID- 9582034
TI  - Serum lipids after a low-fat diet.

PMID- 9582035
TI  - The role of the psychiatrist in a patient's request to die.

PMID- 9582036
TI  - The emerging tobacco epidemic in China.

PMID- 9582037
TI  - The emerging tobacco epidemic in China.

PMID- 9582038
TI  - Risk of injury among workers with disability.

PMID- 9582039
TI  - Risk of injury among workers with disability.

PMID- 9582040
TI  - Risk of injury among workers with disability.

PMID- 9582041
TI  - Risk of injury among workers with disability.

PMID- 9582042
TI  - Improving the quality of care for Medicare patients with acute myocardial
      infarction: results from the Cooperative Cardiovascular Project.
AB  - CONTEXT: Medicare has a legislative mandate for quality assurance, but the
      effectiveness of its population-based quality improvement programs has been
      difficult to establish. OBJECTIVE: To improve the quality of care for Medicare
      patients with acute myocardial infarction. DESIGN: Quality improvement project
      with baseline measurement, feedback, remeasurement, and comparison samples.
      SETTING: All acute care hospitals in the United States. PATIENTS: Preintervention
      and postintervention samples included all Medicare patients in Alabama,
      Connecticut, Iowa, and Wisconsin discharged with principal diagnoses of acute
      myocardial infarctions during 2 periods, June 1992 through December 1992 and
      August 1995 through November 1995. Indicator comparisons were made with a random
      sample of Medicare patients in the rest of the nation discharged with acute
      myocardial infarctions from August 1995 through November 1995. Mortality
      comparisons involved all Medicare patients nationwide with inpatient claims for
      acute myocardial infarctions during 2 periods, June 1992 through May 1993 and
      August 1995 through July 1996. INTERVENTION: Data feedback by peer review
      organizations. MAIN OUTCOME MEASURES: Quality indicators derived from clinical
      practice guidelines, length of stay, and mortality. RESULTS: Performance on all
      quality indicators improved significantly in the 4 pilot states. Administration
      of aspirin during hospitalization in patients without contraindications improved
      from 84% to 90% (P< .001), and prescription of beta-blockers at discharge
      improved from 47% to 68% (P < .001). Mortality at 30 days decreased from 18.9% to
      17.1% (P = .005) and at 1 year from 32.3% to 29.6% (P < .001). These improvements
      in quality occurred during a period when median length of stay decreased from 8
      days to 6 days. Performance on all quality indicators except reperfusion was
      better in the pilot states than in the rest of the nation in 1995, and the
      differences were statistically significant for aspirin use at discharge (P <
      .001), beta-blocker use (P < .001), and smoking cessation counseling (P = .02).
      Postinfarction mortality was not significantly different between the pilot states
      and the rest of the nation during the baseline period, although it was slightly
      but significantly better in the pilot states during the follow-up period
      (absolute mortality difference at 1 year, 0.9%; P = .004). CONCLUSIONS: The
      quality of care for Medicare patients with acute myocardial infarction has
      improved in the Cooperative Cardiovascular Project pilot states. Performance on
      the defined quality indicators appeared to be better in the pilot states than in
      the rest of the nation in 1995 and was associated with reduced mortality.

PMID- 9582043
TI  - Effect of local medical opinion leaders on quality of care for acute myocardial
      infarction: a randomized controlled trial.
AB  - CONTEXT: The effectiveness of recruiting local medical opinion leaders to improve
      quality of care is poorly understood. OBJECTIVE: To evaluate a guideline
      implementation intervention of clinician education by local opinion leaders and
      performance feedback to (1) increase use of lifesaving drugs (aspirin and
      thrombolytics in eligible elderly patients, beta-blockers in all eligible
      patients) for acute myocardial infarction (AMI), and (2) decrease use of a
      potentially harmful therapy (prophylactic lidocaine). DESIGN: Randomized
      controlled trial with hospital as the unit of randomization, intervention, and
      analysis. SETTING: Thirty-seven community hospitals in Minnesota. PATIENTS: All
      patients with AMI admitted to study hospitals over 10 months before (1992-1993,
      N=2409) or after (1995-1996, N=2938) the intervention. INTERVENTION: Using a
      validated survey, we identified opinion leaders at 20 experimental hospitals who
      influenced peers through small and large group discussions, informal
      consultations, and revisions of protocols and clinical pathways. They focused on
      (1) evidence (drug efficacy), (2) comparative performance, and (3) barriers to
      change. Control hospitals received mailed performance feedback. MAIN OUTCOME
      MEASURES: Hospital-specific changes before and after the intervention in the
      proportion of eligible patients receiving each study drug. RESULTS: Among
      experimental hospitals, the median change in the proportion of eligible elderly
      patients receiving aspirin was +0.13 (17% increase from 0.77 at baseline),
      compared with a change of -0.03 at control hospitals (P=.04). For beta-blockers,
      the respective changes were +0.31 (63% increase from 0.49 at baseline) vs +0.18
      (30% increase from baseline) for controls (P=.02). Lidocaine use declined by
      about 50% in both groups. The intervention did not increase thrombolysis in the
      elderly (from 0.73 at baseline), but nearly two thirds of eligible nonrecipients
      were older than 85 years, had severe comorbidities, or presented after at least 6
      hours. CONCLUSIONS: Working with opinion leaders and providing performance
      feedback can accelerate adoption of some beneficial AMI therapies (eg, aspirin,
      beta-blockers). Secular changes in knowledge and hospital protocols may
      extinguish outdated practices (eg, prophylactic lidocaine). However, it is more
      difficult to increase use of effective but riskier treatments (eg, thrombolysis)
      for frail elderly patients.

PMID- 9582044
TI  - The generalist role of specialty physicians: is there a hidden system of primary
      care?
AB  - CONTEXT: Despite increased emphasis on primary care in the United States, most
      care continues to be provided by specialists. The extent to which specialists
      incorporate elements of primary care in their approach to ambulatory patients is
      unknown. OBJECTIVES: To examine the extent to which selected medical and surgical
      subspecialties provide generalist care to Medicare patients, and to compare
      patterns of care between specialists and generalists. DESIGN: A cross-sectional
      study of all ambulatory care recorded in Part B of the Washington State Medicare
      Claims Database in 1994 and 1995. SETTING: Ambulatory practices in Washington
      State. PATIENTS: Medicare beneficiaries 65 years or older who made office visits
      to the study physicians. MAIN OUTCOME MEASURES: The extent to which individual
      specialties accounted for the majority of visits made by patients to physicians
      (a measure of continuity), provided care outside the traditional domain of their
      specialty (a measure of comprehensiveness), and provided influenza immunization.
      RESULTS: A total of 373 505 patients constituted the sample. Patients had an
      average of 7.48 outpatient visits per year; 9.6% saw only generalists, while
      14.7% saw only specialists. The practices of general internists and family
      physicians differ systematically from the practices of most specialists.
      Approximately half (49.8%) of all ambulatory visits to general internists and
      family physicians are made by patients for whom they provide the majority of
      outpatient care, compared with 21.0% of medical specialist and 11.7% of surgical
      specialist visits. The rate of influenza immunization was 55.4% for patients who
      received the majority of their care from generalists, 47.7% from medical
      specialists, and 39.6% from surgical specialists. Pulmonologists, general
      surgeons, and gynecologists were more likely than other specialists to provide
      services outside their specialty. CONCLUSIONS: Most specialists do not assume the
      principal care responsibility for elderly patients, although a substantial
      proportion of patients see only specialists for their care. Selected specialties
      assume the generalist role more often, particularly when they provide the
      majority of outpatient care for an individual patient.

PMID- 9582045
TI  - Cost-effectiveness analysis of a rotavirus immunization program for the United
      States.
AB  - CONTEXT: Rotavirus is the most common cause of severe diarrhea in children, and a
      live, oral vaccine may soon be licensed for prevention. OBJECTIVE: To estimate
      the economic impact of a national rotavirus immunization program in the United
      States. DESIGN: Cost-effectiveness was analyzed from the perspectives of the
      health care system and society. A decision tree used estimates of disease burden,
      costs, vaccine coverage, efficacy, and price obtained from published and
      unpublished sources. INTERVENTION: The proposed vaccine would be administered to
      infants at ages 2, 4, and 6 months as part of the routine schedule of childhood
      immunizations. MAIN OUTCOME MEASURES: Total costs, outcomes prevented, and
      incremental cost-effectiveness. RESULTS: A routine, universal rotavirus
      immunization program would prevent 1.08 million cases of diarrhea, avoiding 34000
      hospitalizations, 95000 emergency department visits, and 227000 physician visits
      in the first 5 years of life. At $20 per dose, the program would cost $289
      million and realize a net loss of $107 million to the health care system-$103 per
      case prevented. The program would provide a net savings of $296 million to
      society. Threshold analysis identified a break-even price per dose of $9 for the
      health care system and $51 for the societal perspective. Greater disease burden
      and greater vaccine efficacy and lower vaccine price increased cost
      effectiveness. CONCLUSIONS: A US rotavirus immunization program would be cost
      effective from the perspectives of society and the health care system, although
      the cost of the immunization program would not be fully offset by the reduction
      in health care cost of rotavirus diarrhea unless the price fell to $9 per dose.

PMID- 9582046
TI  - A conceptual model of the effects of health care organizations on the quality of
      medical care.
AB  - There has been a great deal of interest in recent years in developing measures of
      health care quality that can be used to characterize and study the effects of
      health plans. However, because of the recent emergence of diverse types of health
      care organizations, it is often difficult to know which parts of a plan should be
      combined for analysis purposes. Also, simple taxonomies of health maintenance
      organizations (eg, staff, independent practice associations, group, and network)
      no longer adequately describe the diverse types of organizations that have become
      common. In this article we describe these trends, explain why older taxonomies of
      health care plans are not adequate, and present a new framework for
      characterizing and studying the effects of diverse types of plans.

PMID- 9582047
TI  - Effects of sodium restriction on blood pressure, renin, aldosterone,
      catecholamines, cholesterols, and triglyceride: a meta-analysis.
AB  - CONTEXT: One of the controversies in preventive medicine is whether a general
      reduction in sodium intake can decrease the blood pressure of a population and
      thereby reduce the number of strokes and myocardial infarctions. In recent years
      the debate has been extended by studies indicating that reduced sodium intake has
      adverse effects. OBJECTIVE: To estimate the effects of reduced sodium intake on
      systolic and diastolic blood pressure (SBP and DBP), body weight, and plasma or
      serum levels of renin, aldosterone, catecholamines, cholesterols, and
      triglyceride, and to evaluate the stability of the blood pressure effect in
      relation to additional trials. DATA SOURCES: MEDLINE search from 1966 through
      December 1997 and reference lists of relevant articles. STUDY SELECTION: Studies
      randomizing persons to high-sodium and low-sodium diets were included if they
      evaluated at least one of the effect parameters. DATA EXTRACTION: Two authors
      independently recorded data. DATA SYNTHESIS: In 58 trials of hypertensive
      persons, the effect of reduced sodium intake as measured by urinary sodium
      excretion (mean, 118 mmol/24 h) on SBP was 3.9 mm Hg (95% confidence interval
      [CI], 3.0-4.8 mm Hg) (P<.001) and on DBP was 1.9 mm Hg (95% CI, 1.3-2.5 mm Hg)
      (P<.001). In 56 trials of normotensive persons, the effect of reduced sodium
      intake (mean, 160 mmol/24 h) on SBP was 1.2 mm Hg (95% CI, 0.6-1.8 mm Hg)
      (P<.001) and on DBP was 0.26 mm Hg (95% CI, -0.3-0.9 mm Hg) (P=.12). The
      cumulative analysis showed that this effect size has been stable since 1985. In
      plasma, the renin level increased 3.6-fold (P<.001), and the aldosterone level
      increased 3.2-fold (P<.001); the increases were proportional to the degree of
      sodium reduction for both renin (r=0.66; P<.001) and aldosterone (r=0.64;
      P<.001). Body weight decreased significantly, and noradrenaline, cholesterol, and
      low-density lipoprotein cholesterol levels increased. There was no effect on
      adrenaline, triglyceride, and high-density lipoprotein cholesterol. CONCLUSION:
      These results do not support a general recommendation to reduce sodium intake.
      Reduced sodium intake may be used as a supplementary treatment in hypertension.
      Further long-term studies of the effects of high reduction of sodium intake on
      blood pressure and metabolic variables may clarify the disagreements as to the
      role of reduced sodium intake, but ideally trials with hard end points such as
      morbidity and survival should end the controversy.

PMID- 9582048
TI  - Better care and better outcomes: the continuing challenge.

PMID- 9582049
TI  - Primary care and the specialist.

PMID- 9582050
TI  - Contempo new and now: updates linking evidence and experience.

PMID- 9582051
TI  - Alternative careers for physicians.

PMID- 9582052
TI  - Physicians enter the job market.

PMID- 9582054
TI  - Everywhere and then some: physicians making careers in biopharmaceuticals.

PMID- 9582053
TI  - The power of the pen: medical journalism and public awareness.

PMID- 9582055
TI  - Physician surplus: the Czech story.

PMID- 9582056
TI  - Family medicine: a call to the front line.

PMID- 9582058
TI  - Jewish leaders meet NIH chiefs on genetic stigmatization fears.

PMID- 9582059
TI  - Success prompts bid for second Neurolab launch.

PMID- 9582060
TI  - Troubled UK biotech firm faces new probe.

PMID- 9582061
TI  - Banned drug 'still used until this month'.

PMID- 9582063
TI  - Tycho's illusion and human cognition.

PMID- 9582062
TI  - Unesco board set to agree compromise on bioethics committee.

PMID- 9582064
TI  - A marriage of bone and nacre.

PMID- 9582065
TI  - Calcium signalling. Oscillation, activation, expression.

PMID- 9582066
TI  - Neuropharmacology. Premenstrual steroids?

PMID- 9582067
TI  - Molecular clocks: mastering time by gene regulation.

PMID- 9582068
TI  - Allosteric effects of DNA on transcriptional regulators.
AB  - Selective gene transcription is mediated in part by regulatory proteins that bind
      to DNA response elements. These regulatory proteins receive global information
      from signal-transduction events. But transcriptional regulators may also be
      modified in an allosteric manner by response elements themselves to generate the
      pattern of regulation that is appropriate to an individual gene.

PMID- 9582069
TI  - Accretion rate of cosmic spherules measured at the South Pole.
AB  - Micrometeorites are terrestrially collected, extraterrestrial particles smaller
      than about 1 mm, which account for most of the mass being accreted to the Earth.
      Compared with meteorites, micrometeorites more completely represent the Earth
      crossing meteoroid complex and should include fragments of asteroids, comets,
      Mars and our Moon, as well as pre-solar and interstellar grains. Previous
      measurements of the flux of micrometeoroids that survive to the Earth's surface
      have large uncertainties owing to the destruction of particles by weathering,
      inefficiencies in magnetic collection or separation techniques, low particle
      counts, poor age constraint or highly variable concentrating processes. Here we
      describe an attempt to circumvent these problems through the collection of
      thousands of well preserved and dated micrometeorites from the bottom of the
      South Pole water well, which supplies drinking water for the Scott-Amundsen
      station. Using this collection, we have determined precise estimates of the flux
      and mass distribution for 50-700-microm cosmic spherules (melted
      micrometeorites). Allowing for the expected abundance of unmelted micrometeorites
      in the samples, our results indicate that about 90% of the incoming mass of
      submillimetre particles evaporates during atmospheric entry. Our data indicate
      the loss of glass-rich and small stony spherules from deep-sea deposits, and they
      provide constraints for models describing the survival probability of
      micrometeoroids.

PMID- 9582070
TI  - A molecular timescale for vertebrate evolution.
AB  - A timescale is necessary for estimating rates of molecular and morphological
      change in organisms and for interpreting patterns of macroevolution and
      biogeography. Traditionally, these times have been obtained from the fossil
      record, where the earliest representatives of two lineages establish a minimum
      time of divergence of these lineages. The clock-like accumulation of sequence
      differences in some genes provides an alternative method by which the mean
      divergence time can be estimated. Estimates from single genes may have large
      statistical errors, but multiple genes can be studied to obtain a more reliable
      estimate of divergence time. However, until recently, the number of genes
      available for estimation of divergence time has been limited. Here we present
      divergence-time estimates for mammalian orders and major lineages of vertebrates,
      from an analysis of 658 nuclear genes. The molecular times agree with most early
      (Palaeozoic) and late (Cenozoic) fossil-based times, but indicate major gaps in
      the Mesozoic fossil record. At least five lineages of placental mammals arose
      more than 100 million years ago, and most of the modern orders seem to have
      diversified before the Cretaceous/Tertiary extinction of the dinosaurs.

PMID- 9582071
TI  - The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster.
AB  - Genes of the Hox cluster are restricted to the animal kingdom and play a central
      role in axial patterning in divergent animal phyla. Despite its evolutionary and
      developmental significance, the origin of the Hox gene cluster is obscure. The
      consensus is that a primordial Hox cluster arose by tandem gene duplication close
      to animal origins. Several homeobox genes with high sequence identity to Hox
      genes are found outside the Hox cluster and are known as 'dispersed' Hox-like
      genes; these genes may have been transposed away from an expanding cluster. Here
      we show that three of these dispersed homeobox genes form a novel gene cluster in
      the cephalochordate amphioxus. We argue that this 'ParaHox' gene cluster is an
      ancient paralogue (evolutionary sister) of the Hox gene cluster; the two gene
      clusters arose by duplication of a ProtoHox gene cluster. Furthermore, we show
      that amphioxus ParaHox genes have co-linear developmental expression patterns in
      anterior, middle and posterior tissues. We propose that the origin of distinct
      Hox and ParaHox genes by gene-cluster duplication facilitated an increase in body
      complexity during the Cambrian explosion.

PMID- 9582072
TI  - Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation.
AB  - Primary or nonspecific X-linked mental retardation (MRX) is a heterogeneous
      condition in which affected patients do not have any distinctive clinical or
      biochemical features in common apart from cognitive impairment. Although it is
      present in approximately 0.15-0.3% of males, most of the genetic defects
      associated with MRX, which may involve more than ten different genes, remain
      unknown. Here we report the characterization of a new gene on the long arm of the
      X-chromosome (position Xq12) and the identification in unrelated individuals of
      different mutations that are predicted to cause a loss of function. This gene is
      highly expressed in fetal brain and encodes a protein of relative molecular mass
      91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase
      activating protein (rhoGAP). By enhancing their GTPase activity, GAP proteins
      inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might
      cause constitutive activation of their GTPase targets. Such activation is known
      to affect cell migration and outgrowth of axons and dendrites in vivo. Our
      results demonstrate an association between cognitive impairment and a defect in a
      signalling pathway that depends on a Ras-like GTPase.

PMID- 9582073
TI  - GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an
      endogenous steroid.
AB  - The hormone progesterone is readily converted to 3alpha-OH-5alpha-pregnan-20-one
      (3alpha,5alpha-THP) in the brains of males and females. In the brain,
      3alpha,5alpha-THP acts like a sedative, decreasing anxiety and reducing seizure
      activity, by enhancing the function of GABA (gamma-aminobutyric acid), the
      brain's major inhibitory neurotransmitter. Symptoms of premenstrual syndrome
      (PMS), such as anxiety and seizure susceptibility, are associated with sharp
      declines in circulating levels of progesterone and, consequently, of levels of
      3alpha,5alpha-THP in the brain. Abrupt discontinuation of use of sedatives such
      as benzodiazepines and ethanol can also produce PMS-like withdrawal symptoms.
      Here we report a progesterone-withdrawal paradigm, designed to mimic PMS and post
      partum syndrome in a rat model. In this model, withdrawal of progesterone leads
      to increased seizure susceptibility and insensitivity to benzodiazepine sedatives
      through an effect on gene transcription. Specifically, this effect was due to
      reduced levels of 3alpha,5alpha-THP which enhance transcription of the gene
      encoding the alpha4 subunit of the GABA(A) receptor. We also find that increased
      susceptibility to seizure after progesferone withdrawal is due to a sixfold
      decrease in the decay time for GABA currents and consequent decreased inhibitory
      function. Blockade of the alpha4 gene transcript prevents these withdrawal
      properties. PMS symptoms may therefore be attributable, in part, to alterations
      in expression of GABA(A) receptor subunits as a result of progesterone
      withdrawal.

PMID- 9582074
TI  - Modifying the mechanical property and shear threshold of L-selectin adhesion
      independently of equilibrium properties.
AB  - Interactions between adhesion molecules on two different cells differ from
      interactions between receptors and soluble ligands in that the adhesion molecule
      interaction (bond) is often subjected to force. It is widely assumed by cell
      biologists that the 'strength' of a bond is a simple function of the affinity of
      one adhesion molecule for the other, whereas biophysicists suggest that bonds
      have 'mechanical properties' that affect their strength. Mechanical properties
      are a function of the shape of the energy landscape related to bond formation and
      dissociation, whereas affinity is related only to the net energy change.
      Mechanical properties determine the amount by which the kinetics and affinity of
      bonds are altered by applied force. To date there has been no experimental
      manipulation of an adhesion molecule that has been shown to affect mechanical
      properties. L-selectin is an adhesion molecule that mediates lymphocyte binding
      to, and rolling on, high endothelial venules; these are prerequisites for the
      emigration of lymphocytes from the bloodstream into lymph nodes. Here we report a
      selective and reversible chemical modification of a mucin-like ligand that alters
      the mechanical properties of its bond with L-selectin. The effect of force on the
      rate of bond dissociation, that is, on a mechanical property, is altered, whereas
      there is little or no effect of the modification on the rate of bond dissociation
      in the absence of force. Moreover, the puzzling requirement for hydrodynamic
      shear flow above a threshold level for L-selectin interactions is dramatically
      altered.

PMID- 9582075
TI  - Calcium oscillations increase the efficiency and specificity of gene expression.
AB  - Cytosolic calcium ([Ca2+]i) oscillations are a nearly universal mode of
      signalling in excitable and non-excitable cells. Although Ca2+ is known to
      mediate a diverse array of cell functions, it is not known whether oscillations
      contribute to the efficiency or specificity of signalling or are merely an
      inevitable consequence of the feedback control of [Ca2+]i. We have developed a
      Ca2+ clamp technique to investigate the roles of oscillation amplitude and
      frequency in regulating gene expression driven by the proinflammatory
      transcription factors NF-AT, Oct/OAP and NF-kappaB. Here we report that
      oscillations reduce the effective Ca2+ threshold for activating transcription
      factors, thereby increasing signal detection at low levels of stimulation. In
      addition, specificity is encoded by the oscillation frequency: rapid oscillations
      stimulate all three transcription factors, whereas infrequent oscillations
      activate only NF-kappaB. The genes encoding the cytokines interleukin (IL)-2 and
      IL-8 are also frequency-sensitive in a way that reflects their degree of
      dependence on NF-AT versus NF-kappaB. Our results provide direct evidence that
      [Ca2+]i oscillations increase both the efficacy and the information content of
      Ca2+ signals that lead to gene expression and cell differentiation.

PMID- 9582076
TI  - Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene
      expression.
AB  - Inositol 1,4,5-trisphosphate (InsP3) releases calcium from intracellular stores
      and triggers complex waves and oscillations in levels of cytosolic free calcium.
      To determine which longer-term responses are controlled by oscillations in InsP3
      and cytosolic free calcium, it would be useful to deliver exogenous InsP3, under
      spatial and temporal control, into populations of unpermeabilized cells. Here we
      report the 15-step synthesis of a membrane-permeant, caged InsP3 derivative from
      myo-inositol This derivative diffused into intact cells and was hydrolysed to
      produce a caged, metabolically stable InsP3 derivative. This latter derivative
      accumulated in the cytosol at concentrations of hundreds of micromolar, without
      activating the InsP3 receptor. Ultraviolet illumination uncaged an InsP3 analogue
      nearly as potent as real InsP3, and generated spikes of cytosolic free calcium,
      and stimulated gene expression via the nuclear factor of activated T cells. The
      same total amount of InsP3 analogue elicited much more gene expression when
      released by repetitive flashes at 1-minute intervals than when released at 0.5-
      or > or = 2-minute intervals, as a single pulse, or as a slow sustained plateau.
      Thus, oscillations in cytosolic free calcium levels at roughly physiological
      rates maximize gene expression for a given amount of InsP3.

PMID- 9582077
TI  - NMR structure and mutagenesis of the FADD (Mort1) death-effector domain.
AB  - When activated, membrane-bound receptors for Fas and tumour-necrosis factor
      initiate programmed cell death by recruiting the death domain of the adaptor
      protein FADD to the membrane. FADD then activates caspase 8 (also known as FLICE
      or MACH) through an interaction between the death-effector domains of FADD and
      caspase 8. This ultimately leads to the apoptotic response. Death-effector
      domains and homologous protein modules known as caspase-recruitment domains have
      been found in several proteins and are important regulators of caspase (FLICE)
      activity and of apoptosis. Here we describe the solution structure of a soluble,
      biologically active mutant of the FADD death-effector domain. The structure
      consists of six antiparallel, amphipathic alpha-helices and resembles the overall
      fold of the death domains of Fas and p75. Despite this structural similarity,
      mutations that inhibit protein-protein interactions involving the Fas death
      domain have no effect when introduced into the FADD death-effector domain.
      Instead, a hydrophobic region of the FADD death-effector domain that is not
      present in the death domains is vital for binding to FLICE and for apoptotic
      activity.

PMID- 9582078
TI  - Crystal structure of the tetramerization domain of the Shaker potassium channel.
AB  - Voltage-dependent, ion-selective channels such as Na+, Ca2+ and K+ channel
      proteins function as tetrameric assemblies of identical or similar subunits. The
      clustering of four subunits is thought to create an aqueous pore centred at the
      four-fold symmetry axis. The highly conserved, amino-terminal cytoplasmic domain
      (approximately 130 amino acids) immediately preceding the first putative
      transmembrane helix S1 is designated T1. It is known to confer specificity for
      tetramer formation, so the heteromeric assembly of K+-channel subunits is an
      important mechanism for the observed channel diversity. We have determined the
      crystal structure of the T1 domain of a Shaker potassium channel at 1.55 A
      resolution. The structure reveals that four identical subunits are arranged in a
      four-fold symmetry surrounding a centrally located pore about 20 A in length.
      Subfamily-specific assembly is provided primarily by polar interactions encoded
      in a conserved set of amino acids at its tetramerization interface. Most highly
      conserved amino acids in the T1 domain of all known potassium channels are found
      in the core of the protein, indicating a common structural framework for the
      tetramer assembly.

PMID- 9582079
TI  - A UVB phototherapy protocol with very low dose increments as a treatment of
      atopic dermatitis.
AB  - From 1991 to 1992, 15 patients with atopic dermatitis were treated with a new UVB
      treatment regimen guided by skin reflectance measurements. The new treatment was
      characterized by very low dose increments from start to end of therapy. The
      median cumulative dose increment during therapy was only 20%. The severity of the
      disease, the efficacy of the treatment, the occurrence of adverse effects and the
      cumulative UVB dose were obtained from the case records. This data were compared
      in an open study with the data obtained from 17 patients with atopic dermatitis
      who were treated from 1988 to 1991 at the department with a standard UVB
      treatment regimen with stepwise dose increments. There was no difference in the
      severity of the disease at the beginning of the therapy between the two groups.
      The skin reflectance-guided low-dose UVB therapy was not significantly faster
      (3.5 weeks) than the regimen with stepwise dose increments (4.5 weeks). The
      cumulative UV exposure was four times lower with the new treatment regimen (34
      standard erythema doses) compared with the old regimen (161 standard erythema
      doses), P<0.001. The healing score was significantly higher with the new
      treatment regimen compared with the old, P<0.05. This study indicates that skin
      reflectance-guided UVB phototherapy may enable the dermatologist to lower the
      cumulative UVB exposure significantly without losing effect.

PMID- 9582080
TI  - Quantification of personal solar UV exposure of outdoor workers, indoor workers
      and adolescents at two locations in Southeast Queensland.
AB  - Quantification of human exposure to solar ultraviolet (UV) radiation at two
      locations was performed to study the effect of occupation (outdoor workers,
      schoolchildren and home workers) and location on personal UV exposure. The study
      took place on 13 and 14 February 1997 in Toowoomba (27.5 degrees S, 151.9 degrees
      E) and Brisbane (27.4 degrees S, 153.1 degrees E) in Southeast Queensland,
      Australia. From the data collected by calibrated ambient UV monitoring stations
      located in Toowoomba and Brisbane, Toowoomba received 16% more UVB (280-320 nm)
      than Brisbane from 07:00 to 17:00 Australian Eastern Standard Time (EST) on the
      13 February, 1997 and 10% more UVB on the 14 February 1997. All groups,
      regardless of occupation, in this study received a median erythemal UV exposure
      of over 2 MED on the shoulder over the 2 day period. The highest median erythemal
      UV exposure to the shoulder over the 2 day period was 6 MED in Toowoomba outdoor
      workers. The median 2 day erythemal exposure to the shoulder was 33% higher in
      Toowoomba than in Brisbane for the outdoor workers, 50% higher in Toowoomba
      compared to Brisbane for the schoolchildren and 25% higher in Toowoomba than
      Brisbane for the home workers.

PMID- 9582081
TI  - Quantitative evaluation of the personal erythemal ultraviolet exposure in a car.
AB  - Erythemal ultraviolet (UV)-radiation exposure to the right hand, mid-arm,
      shoulder, chin, nose and left and right sides of the face has been evaluated in a
      car from a large family class and a car from a small car class. In the small car,
      the site with highest exposure received 2.2 times more radiation than the site
      with the highest exposure in the larger car. In both cars, highest erythemal
      exposures were to the right shoulder, arm, and hand. Over a 6 h period, erythemal
      exposure to the right shoulder of a person in the driver's seat of the small car
      was 3.1 mJ x cm(-2).

PMID- 9582082
TI  - The effect of UVB irradiation on antibody responses during herpes simplex virus
      type 1 (HSV-1) infections of mice.
AB  - Ultraviolet B (UVB) exposure suppresses cell-mediated immunity and may alter the
      cytokine profile, reducing T helper 1 (Th1) cytokines and promoting Th2
      cytokines. Th1 cytokines enhance the production of immunoglobulin (Ig) G2a, IgG2b
      and IgG3 antibodies, while Th2 cytokines enhance the production of IgG1 and IgE
      antibodies. The effect of suberythemal UVB irradiation on antibody isotypes
      following infection of C3H/HeN mice with herpes simplex virus (HSV) was
      investigated using two protocols. First, mice were irradiated prior to two
      subcutaneous infections with HSV. Second, mice were immunised with inactivated
      HSV before being irradiated and challenged epidermally with HSV, which led to an
      increase in the size of the clinical lesions compared with unirradiated animals.
      In both models, the HSV-specific IgG titre was not affected by the UVB exposure
      but, generally, the irradiated animals showed a small reduction in both Th1- and
      Th2-associated HSV antibody isotypes. IL-4 knockout (IL-4-/-) mice were used to
      investigate the role of IL-4 in UVB-induced isotype switching. Here IL-4-/- and
      IL-4+/+ strains were irradiated prior to primary and secondary epidermal
      infections with HSV, followed by measurement of antibody titres and lesion size.
      In both the mutant and parent mice, UV irradiation led to an increase in lesion
      severity. In IL-4+/+ mice, UV exposure did not affect the HSV titre of any of the
      individual isotypes tested but did suppress the total IgG to HSV This suppression
      may be due to UV-induced IL-4 release because, in the IL-4-/- mice, HSV IgG was
      elevated by the UVB irradiation. If UV modulates the immune response solely via
      the action of cytokines, then the downregulation of Th1 cytokines and
      upregulation of Th2 cytokines should be accompanied by antibody isotype switching
      from IgG2a and IgG3 towards IgG1 and IgE. This result was not obtained in the
      models tested, perhaps because HSV infection promotes such a complex array of
      innate and acquired immune responses that a clear effect on virus-specific
      isotype production may not be apparent.

PMID- 9582083
TI  - Relationship between minimal phototoxic dose and skin colour plus sun exposure
      history: a neural network approach.
AB  - Before beginning PUVA-therapy it is important to accurately gauge an individual's
      degree of psoralen photosensitivity. This determination is usually based on an
      individual's skin phototype or minimal phototoxic dose. Since minimal phototoxic
      dose is technically complex and time consuming to measure, sun reactivity skin
      phototype is often used instead; however, it has recently been shown that skin
      phototype lacks specificity as a predictor of an individual's minimal phototoxic
      dose. In this study, an artificial neural network was developed to attempt to
      predict the minimal phototoxic dose from skin colour measurements combined with
      skin phototype. Our results showed that minimal phototoxic dose was predicted
      with an error less than 1 J/cm2 in only about half the subjects. In conclusion,
      minimal phototoxic dose probably cannot be predicted with sufficient accuracy on
      the basis of skin colour and skin phototype alone.

PMID- 9582084
TI  - Morphological and hormonal changes in the ventral and dorsolateral prostatic
      lobes of rats treated with finasteride, a 5-alpha reductase inhibitor.
AB  - BACKGROUND: In rats, the prostate is divided into three distinct lobes, and the
      lobes are dependent on androgens [testosterone (T) and dihydrotestosterone (DHT)]
      as trophic hormones. However, the reasons for the difference in the incidence of
      proliferative changes reported are not well-understood. Administration of
      finasteride, a 5-alpha reductase (5alphaR) inhibitor which selectively inhibits
      the conversion of T to DHT, results in elevated intraprostatic T levels. However,
      long-term (2 years) administration of finasteride results in no increase in
      proliferative changes in the ventral lobes of the rat prostate. Therefore,
      studies were designed to determine the differences in intraprostatic hormonal
      levels, morphology, and 5alphaR activity in different lobes of the rat prostate.
      METHODS: Sexually mature male Sprague-Dawley rats were used in all studies.
      Finasteride was administered orally to rats. The methodology included
      determination of intraprostatic T and DHT levels by radioimmunoassay, qualitative
      and quantitative evaluation of prostatic morphology, and in vitro determination
      of 5alphaR activities in rat prostatic lobes. RESULTS: A significant amount of
      5alphaR activity was observed in the dorsal, ventral, and lateral lobes of the
      rat prostate. Both 5alphaR isozymes (types 1 and 2) were present in all lobes,
      based on 5alphaR activities observed at both acidic and neutral pH. Oral
      administration of finasteride (160 mg/kg/day) for 15 days resulted in significant
      (P < or = 0.001) decreases in intraprostatic DHT levels and increases in T
      levels; when compared to controls, the mean decrease in DHT levels in the ventral
      and the dorsolateral lobes was 86% and 94%, respectively, and the mean increase
      in T levels in the ventral and the dorsolateral lobes was approximately 3 times
      and 20 times, respectively, higher than in controls. Chronic administration of
      finasteride (80 mg/kg/day) for 6 months resulted in significant (P < or = 0.001)
      decreases in the weights of the prostatic lobes, which correlated with
      significant (P < or = 0.001) decreases in the total number of epithelial and
      stromal cells per gland in both the ventral and dorsolateral lobes of the
      prostate. There were no qualitative differences in prostatic morphology between
      the control and finasteride-treated groups. A short-term study in control rats
      exposed to bromodeoxyuridine (Brdu) showed that the number of Brdu-labeled cells
      in the dorsolateral lobe was significantly (P < or = 0.05) greater than in the
      ventral lobe. CONCLUSIONS: This first comparative study has highlighted some of
      the similarities and differences among the prostatic lobes of the rat. Inhibition
      of conversion of T to DHT with finasteride resulted in a significant increase in
      intraprostatic T levels and a significant decrease in DHT levels in rats; despite
      a significant increase in intraprostatic T levels, the prostate remained
      atrophic, indicating that DHT alone has a trophic effect on the prostate.

PMID- 9582085
TI  - Sex hormone-induced prostatic carcinogenesis in the noble rat: the role of
      insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor
      (VEGF) in the development of prostate cancer.
AB  - BACKGROUND: Despite extensive effort, the mechanisms of prostate carcinogenesis
      are still unknown. We report on a modified method which enabled us to induce a
      high incidence of prostate carcinogenesis in the Noble rat and examined the role
      of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor
      (VEGF) and their receptors during sex hormone-induced prostate carcinogenesis.
      METHODS: Noble rats were implanted subcutaneously with a combination of
      testosterone and estradiol capsules for up to 12 months. Animals were sacrificed
      starting at 2 months after implantation, and the prostate gland was removed for
      histopathological and immunohistochemical studies. RESULTS: The results showed
      that hyperplasia/dysplasia was detected as early as 2 months after treatment,
      while carcinoma in situ was induced in 4 months and adenocarcinoma in 7 months.
      Our data suggest that IGF-1, produced by stromal cells in hyperplasia, exerted
      its effects, through a paracrine mode, on epithelial cells which were IGF-1
      receptor (IGF-1R)-positive. The production of IGF-1 appeared to switch to
      epithelial cells in adenocarcinoma, through which it regulated tumor cell growth
      via autocrine mode by binding to IGF-1R of carcinoma cells. On the other hand,
      VEGF was overexpressed in hyperplastic/dysplastic and carcinoma cells, while VEGF
      R was detected in endothelial cells. The results suggest that overexpression of
      VEGF in deranged epithelia and arterial muscle cells may exert its influence on
      stromal angiogenesis and abnormal growth of prostate gland. CONCLUSIONS: A
      modified Noble rat model with a high incidence of prostate carcinogenesis has
      been developed. Using this model, we have further established that IGF-1 and VEGF
      may be the critical regulators in mediating epithelial-stromal interactions in
      sex hormone-induced prostate carcinogenesis.

PMID- 9582086
TI  - Monoclonal antibodies against human prostasomes.
AB  - BACKGROUND: The prostasomes are secreted into the gland ducts of the human
      prostate. At ejaculation, these native prostasomes are expelled with the
      secretions of the prostate and appear in the seminal plasma as seminal
      prostasomes, where they facilitate sperm function in various ways. We have
      designed methods for producing monoclonal anti-prostasome antibodies to be used
      for immunohistochemistry and sequencing analyses of the prostasomes. METHODS: The
      immunogen applied was purified seminal prostasomes placed on small pieces of
      nitrocellulose membranes (prostasome blots) and deposited into the spleen of mice
      for immunization. For screening, both seminal and native prostasomes were used.
      RESULTS: We obtained antibodies which detected native prostasomes both in
      prostatic secretions and in paraffin sections of the prostate. The immunostaining
      demonstrated that all prostate epithelial cells contained prostasomes. They were
      located in the apical parts of the secretory cells and in the gland ducts, while
      the nuclei and the corpora amylacea were unstained. CONCLUSIONS: Using the
      methods described, monoclonal antibodies against native prostasomes were
      produced. In addition to their usefulness in structural and functional studies of
      prostasomes, specific monoclonal antibodies can be used to characterize
      prostasomes by sequencing analyses.

PMID- 9582087
TI  - Role of alphaII(b)beta3 integrin in prostate cancer metastasis.
AB  - BACKGROUND: Integrins participate in cell-cell and cell-matrix interactions. In
      this study we determined whether alphaII(b)beta3 integrin is involved in
      metastasis of human prostate adenocarcinoma cells. METHODS: Prostate
      adenocarcinoma PC-3 and DU-145 cell lines express alphaII(b)beta3. Northern
      blotting, 5'-RACE, and immunofluorescent localization confirmed expression of
      alphaIIb integrin in prostate adenocarcinoma cells. We used orthotopic/ectopic
      site of implantation and lung colonization assays in SCID mice to determine
      whether alphaII(b)beta3 participates in metastatasis of tumor cells. RESULTS:
      Immunofluorescent localization of alphaIIb integrin in fibronectin-adherent DU
      145 and PC-3 cells is remarkably different. In DU-145 cells the integrin
      localizes to focal contact sites, whereas it is predominantly intracellular in PC
      3 cells. Both tumor cell lines are tumorigenic when implanted subcutaneously or
      intraprostatically in SCID mice, but only DU-145 cells injected
      intraprostatically metastasize. Flow cytometry with a mAb directed to
      alphaII(b)beta3 revealed higher expression of alphaII(b)beta3 in DU-145 tumor
      cell suspensions isolated from the prostate when compared to DU-145 tumor cells
      from the subcutis. Function-blocking mAbs to alphaII(b)beta3 inhibit lung
      colonization of tail vein-injected DU-145 cells. CONCLUSIONS: Altogether, the
      data suggest that alphaII(b)beta3 integrin participates in the metastatic
      progression of prostatic adenocarcinoma.

PMID- 9582088
TI  - Three-dimensional ultrastructure of apoptotic nuclei in rat prostatic epithelial
      cells revealed by a quick-freezing and deep-etching method.
AB  - BACKGROUND: To clarify intranuclear apoptotic changes, we have investigated
      chromatin organization in apoptotic nuclei of castrated rat prostatic cells by a
      quick-freezing and deep-etching (QF-DE) method. METHODS: The ventral prostates
      taken from intact and castrated adult male rats were investigated by light
      microscopy, in situ end-labeling (ISEL) technique, conventional electron
      microscopy, and the QF-DE method. RESULTS: In control nuclei, the chromatin
      fibers were uniformly distributed and formed a network structure. In apoptotic
      nuclei, destruction of such chromatin networks was detected, which was clearly
      seen by the QF-DE method. Although it first appeared spotty in the apoptotic
      nucleus, definite destruction of the intranuclear network occurred in the nuclear
      center at later stages, and broken fibrous structures were condensed along the
      nuclear margin. The ISEL technique was applied to the QF-DE method. Localization
      of damaged DNA fragments could three-dimensionally be detected on replica
      membranes. CONCLUSIONS: Intranuclear chromatin organization in apoptotic cell
      death of rat prostates was observed by the QF-DE method. We could examine early
      stage apoptotic nuclei at an electron microscopic level, which would not be
      clarified by other conventional methods.

PMID- 9582089
TI  - Expression of cytokeratin-19 as a marker of neoplastic progression of human
      prostate epithelial cells.
AB  - BACKGROUND: Our earlier studies demonstrated neoplastic transformation of SV40
      immortalized neonatal human prostate epithelial cells (267B1) by fractionated
      doses of ionizing radiation or by introduction of v-ki-ras oncogene. X-ray
      treated 267B1 cells represent three different stages of neoplastic progression:
      nontumorigenic F3-SAC cells that acquired morphological changes and anchorage
      independence when treated with 2 x 2 Gy of X-rays; malignantly transformed 267B1
      XR and 267B1-SXR cells that received 2-Gy doses to a total of 30 Gy. We also
      reported alterations in cell size, morphology, actin stress fibers, and levels of
      actin-binding proteins in these transformed human prostate cells. METHODS: We
      analyzed intermediate filament-nuclear matrix (IF-NM) protein expression in the
      various 267B1 cells as a consequence of neoplastic progression by two-dimensional
      gel electrophoresis and immunofluorescence. RESULTS: Our present study revealed
      that the 267B1 cells experienced progressive changes in their intermediate
      filament protein composition during the process of neoplastic conversion,
      achieved either by X-rays or by ras-oncogene. In particular, we observed a
      stepwise downregulation of cytokeratin-19 in these in vitro transformed 267B1
      cells. CONCLUSIONS: Our data suggest that loss of expression of cytokeratin-19
      accompanied the morphological alterations associated with in vitro neoplastic
      transformation of SV40-immortalized prostate epithelial cells.

PMID- 9582090
TI  - Coexpression of gonadotropic hormones and their corresponding FSH- and LH/CG
      receptors in the human prostate.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) affects the majority of elderly
      men, and prostate cancer is the most common male cancer. Prostatic growth and
      function are thought to be regulated by steroid hormones, primarily androgens and
      estrogens, but nonandrogenic hormones must also be considered. The increasing
      evidence of para/autocrine functions of the gonadotropic glycoprotein-hormones
      (GPH), their allocation to the superfamily of cystine-knot growth factors, and
      luteinizing hormone (LH)/chorionic gonadotropin (CG)-receptor (R) gene expression
      in nongonadal tissues led us to investigate intraprostatic GPH and GPH-R gene
      expression. METHODS AND RESULTS: RT-PCR and subsequent Southern hybridization
      and/or restriction enzyme analysis of BPH and prostatic adenocarcinoma
      demonstrated that all three human (h) gonadotropic hormones, i.e., follicle
      stimulating hormone (FSH), LH, and CG, as well as the corresponding FSH-R and
      LH/CG-R, are transcribed intraprostatically. Significant amounts of the alpha and
      beta subunits of hCG were secreted by short-term primary cultures of human BPH
      tissues, as detected by highly sensitive and specific time-resolved
      immunofluorometric assays (IFMAs). CONCLUSIONS: Our data suggest that prostatic-
      and pituitary-derived GPH act directly on the prostatic gland, particularly FSH
      via the FSH-R, thereby possibly modulating locally acting key hormones and growth
      factors involved in BPH development.

PMID- 9582091
TI  - Overexpression of manganese superoxide dismutase in DU145 human prostate
      carcinoma cells has multiple effects on cell phenotype.
AB  - BACKGROUND: Recent studies suggest that the gene for manganese superoxide
      dismutase (MnSOD) is a candidate tumor-suppressor gene. The present study was
      designed to study the effect of overexpression of MnSOD on cultured human
      prostate carcinoma cells. METHODS: DU145 human prostate carcinoma cells were
      transfected with the cDNA for manganese superoxide dismutase (MnSOD), and two
      clones overexpressing MnSOD activity were subsequently characterized by
      comparison with parental and plasmid control-transfected cells. RESULTS: One
      clone overexpressing MnSOD had no change in other antioxidant enzymes (AEs)
      (nonadapted), while a second clone showed an increase in catalase activity
      (adapted). Sensitivity of parental, plasmid control-transfected, and MnSOD cDNA
      transfected cells to agents that generate oxidative stress correlated with AE
      profiles. Both clones overexpressing MnSOD activity showed increased reactive
      oxygen species levels under basal cell culture conditions. Both clones
      overexpressing MnSOD activity showed inhibition of cell growth in vitro and in
      vivo compared with parental and plasmid control-transfected cells. Flow cytometry
      studies using mitochondrial-specific probes showed equal mitochondrial mass in
      all cell lines, but altered mitochondrial membrane potential in MnSOD
      overexpressing clones compared with parental or plasmid control-transfected
      cells. CONCLUSIONS: Our results suggest novel mechanisms by which MnSOD
      overexpression may modulate the malignant phenotype, with potential applications
      in developing new therapies for prostate cancer.

PMID- 9582092
TI  - A UV-crosslinkable interaction in human U6 snRNA.
AB  - U6 snRNA is the most conserved of all the snRNAs involved in pre-mRNA splicing,
      and likely plays an important role in splicing catalysis. Using a U6 snRNA
      fragment encompassing residues 25-99, we have identified a strong, UV-sensitive
      tertiary intramolecular interaction. A 5' deletion that removed sequences up to
      nt 37 only slightly reduced crosslinking, but further deletion of 11 bases,
      eliminating the nearly invariant ACAGAGA sequence, essentially abolished
      crosslinking, as did deletion of sequences 3' of 82A. The crosslinked residues
      were mapped to 44G in the ACAGAGA sequence and to 81C, the nucleotide at the base
      of the U6 intramolecular helix, opposite the G of the invariant AGC
      trinucleotide. This interaction is striking in that it has the potential to
      juxtapose invariant regions of U6 believed to play critical roles in splicing
      catalysis.

PMID- 9582094
TI  - Recognition of picornavirus internal ribosome entry sites within cells; influence
      of cellular and viral proteins.
AB  - The ability of different picornavirus internal ribosome entry site (IRES)
      elements to direct initiation of protein synthesis has been assayed in different
      cell lines in the presence and absence of viral proteases that inhibit cap
      dependent protein synthesis. Reporter plasmids that express dicistronic mRNAs,
      containing different IRES elements, with the general structure CAT/IRES/LUC, have
      been assayed. In each plasmid, the CAT sequence encodes chloramphenicol acetyl
      transferase and the LUC sequence encodes luciferase. The poliovirus (PV) 2A
      protease and the foot-and-mouth disease virus (FMDV) Lb protease induce the
      cleavage of the translation initiation factor elF4G and hence inhibit the
      activity of the cap-binding complex, elF4F. In human osteosarcoma (HTK-143)
      cells, each of the various IRES elements functioned efficiently. In these cells,
      the co-expression of the viral proteases severely inhibited the expression of
      CAT, but the proteases had little effect on the activities of the various IRES
      elements. In contrast, in baby hamster kidney (BHK) cells, the efficiencies of
      the different IRES elements varied significantly, whereas, in normal rat kidney
      (NRK) cells, each of the IRES elements was relatively inefficient. In both BHK
      and NRK cells, the activities of those IRES elements that functioned
      inefficiently were strongly stimulated by the co-expression of the PV 2A or FMDV
      Lb proteases. This stimulation was independent of the loss of cap-dependent
      protein synthesis and was not achieved by the co-expression of the C-terminal
      fragment of elF4G. The results suggest that the PV 2A and FMDV Lb proteases
      induce the cleavage of another cellular protein, in addition to elF4G, which
      influences IRES function.

PMID- 9582095
TI  - Group I-like ribozymes with a novel core organization perform obligate sequential
      hydrolytic cleavages at two processing sites.
AB  - A new category of self-splicing group I introns with conserved structural
      organization and function is found among the eukaryotic microorganisms Didymium
      and Naegleria. These complex rDNA introns contain two distinct ribozymes with
      different functions: a regular group I splicing-ribozyme and a small internal
      group I-like ribozyme (GIR1), probably involved in protein expression. GIR1 was
      found to cleave at two internal sites in an obligate sequential order. Both sites
      are located 3' of the catalytic core. GIR1-catalyzed transesterification
      reactions could not be detected. We have compared all available GIR1 sequences
      and propose a common RNA secondary structure resembling that of group I splicing
      ribozymes, but with some important differences. The GIR1s lack most peripheral
      sequence components, as well as a P1 segment, and, at approximately 160-190 nt,
      they are the smallest functional group I ribozymes known from nature. All GIR1s
      were found to contain a novel 6-bp pseudoknot (P15) within their catalytic core
      region. Experimental support of the proposed structure was obtained from the
      Didymium GIR1 by RNA structure probing and site-directed mutagenesis. Three
      dimensional modeling indicates a compactly folded ribozyme with the functionally
      essential P15 exposed in the cleft between the two principal domains P3-P8 and P4
      P6.

PMID- 9582093
TI  - The chemical basis of adenosine conservation throughout the Tetrahymena ribozyme.
AB  - Adenosines are present at a disproportionately high frequency within several RNA
      structural motifs. To explore the importance of individual adenosine functional
      groups for group I intron activity, we performed Nucleotide Analog Interference
      Mapping (NAIM) with a collection of adenosine analogues. This paper reports the
      synthesis, transcriptional incorporation, and the observed interference pattern
      throughout the Tetrahymena group I intron for eight adenosine derivatives tagged
      with an alpha-phosphorothioate linkage for use in NAIM. All of the analogues were
      accurately incorporated into the transcript as an A. The sites that interfere
      with the 3'-exon ligation reaction of the Tetrahymena intron are coincident with
      the sites of phylogenetic conservation, yet the interference patterns for each
      analogue are different. These interference data provide several biochemical
      constraints that improve our understanding of the Tetrahymena ribozyme structure.
      For example, the data support an essential A-platform within the J6/6a region,
      major groove packing of the P3 and P7 helices, minor groove packing of the P3 and
      J4/5 helices, and an axial model for binding of the guanosine cofactor. The data
      also identify several essential functional groups within a highly conserved
      single-stranded region in the core of the intron (J8/7). At four sites in the
      intron, interference was observed with 2'-fluoro A, but not with 2'-deoxy A.
      Based upon comparison with the P4-P6 crystal structure, this may provide a
      biochemical signature for nucleotide positions where the ribose sugar adopts an
      essential C2'-endo conformation. In other cases where there is interference with
      2'-deoxy A, the presence or absence of 2'-fluoro A interference helps to
      establish whether the 2'-OH acts as a hydrogen bond donor or acceptor. Mapping of
      the Tetrahymena intron establishes a basis set of information that will allow
      these reagents to be used with confidence in systems that are less well
      understood.

PMID- 9582096
TI  - Matching the crystallographic structure of ribosomal protein S7 to a three
      dimensional model of the 16S ribosomal RNA.
AB  - Two recently published but independently derived structures, namely the X-ray
      crystallographic structure of ribosomal protein S7 and the "binding pocket" for
      this protein in a three-dimensional model of the 16S rRNA, have been correlated
      with one another. The known rRNA-protein interactions for S7 include a minimum
      binding site, a number of footprint sites, and two RNA-protein crosslink sites on
      the 16S rRNA, all of which form a compact group in the published 16S rRNA model
      (despite the fact that these interactions were not used as primary modeling
      constraints in building that model). The amino acids in protein S7 that are
      involved in the two crosslinks to 16S rRNA have also been determined in previous
      studies, and here we have used these sites to orient the crystallographic
      structure of S7 relative to its rRNA binding pocket. Some minor alterations were
      made to the rRNA model to improve the fit. In the resulting structure, the
      principal positively charged surface of the protein is in contact with the 16S
      rRNA, and all of the RNA-protein interaction data are satisfied. The quality of
      the fit gives added confidence as to the validity of the 16S rRNA model. Protein
      S7 is furthermore known to be crosslinked both to P site-bound tRNA and to mRNA
      at positions upstream of the P site codon; the matched S7-16S rRNA structure
      makes a prediction as to the location of this crosslink site within the protein
      molecule.

PMID- 9582097
TI  - Conservation of functional domains involved in RNA binding and protein-protein
      interactions in human and Saccharomyces cerevisiae pre-mRNA splicing factor SF1.
AB  - The modular structure of splicing factor SF1 is conserved from yeast to man and
      SF1 acts at early stages of spliceosome assembly in both organisms. The hnRNP K
      homology (KH) domain of human (h) SF1 is the major determinant for RNA binding
      and is essential for the activity of hSF1 in spliceosome assembly, supporting the
      view that binding of SF1 to RNA is essential for its function. Sequences N
      terminal to the KH domain mediate the interaction between hSF1 and U2AF65, which
      binds to the polypyrimidine tract upstream of the 3' splice site. Moreover, yeast
      (y) SF1 interacts with Mud2p, the presumptive U2AF65 homologue in yeast, and the
      interaction domain is conserved in ySF1. The C-terminal degenerate RRMs in U2AF65
      and Mud2p mediate the association with hSF1 and ySF1, respectively. Analysis of
      chimeric constructs of hSF1 and ySF indicates that the KH domain may serve a
      similar function in both systems, whereas sequences C-terminal to the KH domain
      are not exchangeable. Thus, these results argue for hSF1 and ySF1, as well as
      U2AF65 and Mud2p, being functional homologues.

PMID- 9582098
TI  - Dbp7p, a putative ATP-dependent RNA helicase from Saccharomyces cerevisiae, is
      required for 60S ribosomal subunit assembly.
AB  - Putative ATP-dependent RNA helicases are ubiquitous, highly conserved proteins
      that are found in most organisms and they are implicated in all aspects of
      cellular RNA metabolism. Here we present the functional characterization of the
      Dbp7 protein, a putative ATP-dependent RNA helicase of the DEAD-box protein
      family from Saccharomyces cerevisiae. The complete deletion of the DBP7 ORF
      causes a severe slow-growth phenotype. In addition, the absence of Dbp7p results
      in a reduced amount of 60S ribosomal subunits and an accumulation of halfmer
      polysomes. Subsequent analysis of pre-rRNA processing indicates that this 60S
      ribosomal subunit deficit is due to a strong decrease in the production of 27S
      and 7S precursor rRNAs, which leads to reduced levels of the mature 25S and 5.8S
      rRNAs. Noticeably, the overall decrease of the 27S pre-rRNA species is neither
      associated with the accumulation of preceding precursors nor with the emergence
      of abnormal processing intermediates, suggesting that these 27S pre-rRNA species
      are degraded rapidly in the absence of Dbp7p. Finally, an HA epitope-tagged Dbp7
      protein is localized in the nucleolus. We propose that Dbp7p is involved in the
      assembly of the pre-ribosomal particle during the biogenesis of the 60S ribosomal
      subunit.

PMID- 9582099
TI  - In vitro assembly of the mouse U14 snoRNP core complex and identification of a 65
      kDa box C/D-binding protein.
AB  - The eukaryotic nucleolus contains a diverse population of small nucleolar RNAs
      (snoRNAs) that have been categorized into two major families based on
      evolutionarily conserved sequence elements. U14 snoRNA is a member of the larger,
      box C/D snoRNA family and possesses nucleotide box C and D consensus sequences.
      In previous studies, we have defined a U14 box C/D core motif that is essential
      for intronic U14 snoRNA processing. These studies also revealed that nuclear
      proteins that recognize boxes C/D are required. We have now established an in
      vitro U14 snoRNP assembly system to characterize protein binding. Electrophoretic
      mobility-shift analysis demonstrated that all the sequences and structures of the
      box C/D core motif required for U14 processing are also necessary for protein
      binding and snoRNP assembly. These required elements include a base paired 5',3'
      terminal stem and the phylogenetically conserved nucleotides of boxes C and D.
      The ability of other box C/D snoRNAs to compete for protein binding demonstrated
      that the box C/D core motif-binding proteins are common to this family of
      snoRNAs. UV crosslinking of nuclear proteins bound to the U14 core motif
      identified a 65-kDa mouse snoRNP protein that requires boxes C and D for binding.
      Two additional core motif proteins of 55 and 50 kDa were also identified by
      biochemical fractionation of the in vitro-assembled U14 snoRNP complex. Thus, the
      U14 snoRNP core complex is a multiprotein particle whose assembly requires
      nucleotide boxes C and D.

PMID- 9582100
TI  - Chimeric rRNAs containing the GTPase centers of the developmentally regulated
      ribosomal rRNAs of Plasmodium falciparum are functionally distinct.
AB  - The human malaria parasite, Plasmodium falciparum, maintains at least two
      distinct types, A and S, of developmentally controlled ribosomal RNAs. To
      investigate specific functions associated with these rRNAs, we replaced the
      Saccharomyces cerevisiae GTPase domain of the 25S rRNA with GTPase domains
      corresponding to the Plasmodium A- and S-type 28S rRNAs. The A-type rRNA differs
      in a single nonconserved base pair from the yeast GTPase domain. The S-type rRNA
      GTPase domain has three additional changes in highly conserved residues, making
      it unique among all known rRNA sequences. The expression of either A- or S-type
      chimeric rRNA in yeast increased translational accuracy. Yeast containing only A
      type chimeric rRNA and no wild-type yeast rRNA grew at the wild-type level. In
      contrast, S-type chimeric rRNA severely inhibited growth in the presence of wild
      type yeast rRNA, and caused lethality in the absence of the wild-type yeast rRNA.
      We show what before could only be hypothesized, that the changes in the GTPase
      center of ribosomes present during different developmental stages of Plasmodium
      species can result in fundamental changes in the biology of the organism.

PMID- 9582101
TI  - Obesity induced by neonatal monosodium glutamate treatment in spontaneously
      hypertensive rats: an animal model of multiple risk factors.
AB  - The present study was designed to develop an animal model of multiple risk
      factors, including obesity, hypertension, non-insulin-dependent diabetes
      mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal
      monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR).
      Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight
      of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not
      in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance,
      hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension
      was attenuated in obese SHR as compared with control SHR. The degree of obesity
      was closely related to the metabolic abnormalities, but inversely correlated with
      the blood pressure level. Macrovascular changes were investigated in obese SHR at
      14 months of age. Intimal thickening was accelerated in the carotid artery of
      obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total
      cholesterol were significantly increased in obese SHR. SHR associated with MSG
      induced obesity showed major manifestations of metabolic syndrome X. This animal
      model may be useful to study the clustering of risk factors for the development
      of macrovascular diseases.

PMID- 9582102
TI  - Effects of intravenously administered C-type natriuretic peptide in humans:
      comparison with atrial natriuretic peptide.
AB  - We have previously reported that C-type natriuretic peptide (CNP), the third
      member of the natriuretic peptide family, is produced in vascular endothelial
      cells and suggested that CNP might be a local regulator of vascular tone and
      growth. To evaluate the biological actions of CNP as compared with human atrial
      natriuretic peptide (hANP), we intravenously administered synthetic CNP (0.43
      nmol/kg) and alpha-hANP (0.43 and 0.043 nmol/kg) to healthy humans. The
      experiments were done on different days in the same five healthy volunteers (31+/
      1 yr old). CNP injection caused a transient but significant decrease in both
      systolic and diastolic blood pressure (-4.3+/-1.3, -4.1+/-1.0 mmHg) with a
      significant increase in heart rate (+7.6+/-2.6 bpm), and exerted significant
      diuretic and natriuretic activities (+130+/-80%, +160+/-100% over the basal
      level). These effects of CNP (0.43 nmol/kg) were comparable to, or less than,
      those of alpha-hANP (0.043 nmol/kg). CNP injection also significantly suppressed
      aldosterone secretion (22% reduction as compared with the basal level). Our
      results demonstrate that intravenously-administered CNP acts as a natriuretic
      peptide with less potency than ANP.

PMID- 9582103
TI  - Responses of natriuretic peptides to acute and chronic salt loading in
      normotensive and hypertensive subjects.
AB  - Responses of endocrine systems to acute and chronic salt loading were examined in
      normotensive and hypertensive subjects. In the acute salt load study, isotonic
      saline (20 ml/kg for 1 h) was intravenously infused in 10 normotensive subjects
      and 12 patients with essential hypertension. Plasma noradrenaline was suppressed
      by saline infusion in the normotensive subjects (-19%, p < 0.05), but was not
      suppressed in the hypertensive patients (-5%, NS). Plasma brain natriuretic
      peptide concentration was significantly increased in the hypertensive patients
      (+15%, p<0.05), while it was unchanged in the normotensive subjects. In the
      chronic salt load study, 9 normotensive subjects and 30 patients with essential
      hypertension underwent two 7-d periods of 30 and 260 mmol/d sodium intake. On the
      basis of the blood pressure change, 17 hypertensive patients were classified as
      salt-resistant and 13 as salt-sensitive. The salt-sensitive hypertensive patients
      had suppressed plasma renin activity even during low-salt intake. During high
      salt intake, the plasma noradrenaline concentration failed to decrease in the
      salt-sensitive hypertensive patients (-6%, NS), whereas it fell significantly in
      the normotensive subjects (-27%, p < 0.05) and the salt-resistant hypertensive
      patients (-33%, p < 0.01). The high-salt intake also increased plasma
      concentrations of brain natriuretic peptide as well as atrial natriuretic peptide
      in all groups. In the salt-sensitive hypertensive patients, there was a positive
      correlation between the increase in blood pressure and that in atrial natriuretic
      peptide (r= 0.84, p< 0.01). These data indicate that brain natriuretic peptide is
      involved in chronic changes in body fluid volume. In patients with essential
      hypertension, acute volume expansion also evokes the response of brain
      natriuretic peptide. Salt-sensitive hypertension seems to be characterized by
      blunted response of the sympathetic nervous system. In addition, an increase in
      atrial natriuretic peptide is likely to play an important role in mechanisms
      counteracting salt-induced elevation of blood pressure.

PMID- 9582104
TI  - Decrease in circulating and urine adrenomedullin concentrations in stroke-prone
      spontaneously hypertensive rats.
AB  - Adrenomedullin (AM) is a peptide with potent vasodilatory and hypotensive
      properties. Plasma AM levels in rats with experimentally induced hypertension,
      such as Dahl salt-sensitive rats and two-kidney, one-clip hypertensive rats, are
      higher than those in normotensive rats. We previously noted, however, that plasma
      AM levels in spontaneously hypertensive rats (SHR) are similar to those in Wistar
      Kyoto rats. To define the role of AM in rats with severe hypertension, we
      investigated changes in circulating and tissue AM levels in stroke-prone
      spontaneously hypertensive rats (SHRSP/Izm). The immunoreactive rat AM levels in
      plasma, urine, and tissue measured with a sensitive radioimmunoassay, and the AM
      mRNA levels in various tissues in 15-wk-old SHRSP/Izm were compared with those in
      age-matched Wistar-Kyoto rats (WKY/Izm). The plasma and urinary AM levels in
      SHRSP/Izm were significantly lower than those in WKY/Izm [plasma AM, 2.14+/-0.06
      (SE) vs. 3.24+/-0.16 fmol/ml, p< 0.001; urinary AM, 16.36+/-3.21 vs. 36.12+/-6.09
      fmol/ml, p< 0.01]. A negative correlation was found between the plasma AM level
      and the systolic blood pressure in both SHRSP/Izm and WKY/Izm. Reverse-phase high
      performance liquid chromatography showed that the molecular components of plasma
      immunoreactive AM in SHRSP/Izm were similar to those in WKY/Izm. Furthermore,
      tissue AM levels in various organs in SHRSP/Izm were not lower than those in
      WKY/Izm. In conclusion, low levels of circulating AM may contribute to the
      maintenance of high blood pressure in 15-wk-old SHRSP/Izm. These low plasma AM
      levels may be caused by accelerated metabolism of circulating AM in SHRSP/Izm.

PMID- 9582105
TI  - Polymorphism of alpha-adducin in Japanese patients with essential hypertension.
AB  - Recently, a molecular variant of alpha-adducin (with tryptophan instead of
      glycine at amino acid number 460) has been reported to be more common among
      Italian and French hypertensive individuals than among controls. Moreover,
      hypertensive individuals with Trp460 exhibit a greater sensitivity to changes in
      sodium balance and a greater fall in blood pressure in response to diuretic
      treatment. In the present study, we investigated the association between
      Gly460Trp polymorphism of the alpha-adducin gene and hypertension in Japanese
      subjects. The study population comprised 283 subjects enrolled at our outpatient
      clinic. The subjects were divided into normotensive (NT), borderline (B), and
      hypertensive (HT) groups. The alpha-adducin genotype was determined by allele
      specific oligonucleotide hybridization. The genotype frequency of Gly460Trp
      polymorphism differed significantly among the NT, B, and HT groups (p=0.0113).
      The GG genotype of the adducin gene was more common in the NT group than in the
      HT group. Moreover, the Trp460 allele was significantly associated with lower
      plasma renin activity (p = 0.0075). However, this polymorphism was unrelated to
      left ventricular mass and height as assessed by echocardiography. The present
      study suggests that Gly460Trp polymorphism of the a-adducin gene may be involved
      in hypertension, particularly the low-renin type, in Japanese individuals.

PMID- 9582106
TI  - L-type calcium channels in vascular smooth muscle cells from spontaneously
      hypertensive rats: effects of calcium agonist and antagonist.
AB  - Studies using the whole-cell voltage-clamp technique have demonstrated that L
      type Ca2+ channel activity is increased in vascular smooth muscle cells from
      spontaneously hypertensive rats (SHR). We recorded L-type Ca2+ channel currents
      in cultured mesenteric artery smooth muscle cells from SHR and Wistar Kyoto (WKY)
      rats by using the cell-attached patch-clamp technique. Depolarizing voltage steps
      from a holding potential of -40 mV elicited voltage-dependent inward Ba2+
      currents. There was no difference in the L-type Ca2+ channel I-V curve or in the
      open probability between SHR and WKY. The inward currents were inhibited by the
      Ca2+ antagonists nifedipine and verapamil, but were enhanced by the Ca2+ agonist
      Bay K 8644 in a concentration-dependent manner. The Bay K 8644-induced increase
      and the nifedipine-induced inhibition of the inward currents were enhanced in
      SHR, whereas there was no difference in the verapamil-induced inhibition of the
      currents between the two strains of rats. These results suggest that the enhanced
      L-type Ca2+ channel activity observed in vascular smooth muscle cells from SHR is
      not due to altered function of a single L-type Ca2+ channel. It appears that the
      sensitivity of dihydropyridine receptors in the channels is enhanced in SHR.

PMID- 9582107
TI  - Role of the renin-angiotensin system in cardiac hypertrophy and renal glomerular
      sclerosis in transgenic hypertensive mice carrying both human renin and
      angiotensinogen genes.
AB  - Tsukuba hypertensive mice (THMs) are transgenic mice carrying human renin and
      angiotensinogen genes. The aim of this study was to evaluate the role of the
      renin-angiotensin system (RAS) in cardiac hypertrophy and renal disorders in
      THMs. After a 2-wk control period, 10-wk-old THMs were treated with lisinopril
      (ACEI group) or hydralazine (hydralazine group) or left untreated (control group)
      for 8 wk. C57BL/6 mice of similar age (wild group) were used as normal controls.
      Systolic blood pressure and urinary albumin excretion were measured once a week.
      All mice were sacrificed at 20 wk of age, and heart to body weight ratio, cardiac
      myocyte diameter, renal glomerular sclerosis index, and glomerular size were
      measured. Fibronectin expression was also evaluated. At 20 wk of age, systolic
      blood pressure and urinary albumin excretion in the control group were
      significantly higher than those in the wild group and significantly lower than
      those in the ACEI and hydralazine groups. Heart to body weight ratio and cardiac
      myocyte diameter were significantly higher in the hydralazine and control groups
      than in the other groups. Renal glomerular sclerosis index and glomerular size
      were also significantly higher in the control group than in the other groups, and
      there were significant differences between the ACEI and hydralazine groups in
      these variables. Fibronectin expression was marked in the control and hydralazine
      groups. These findings suggest that the RAS plays an important role in cardiac
      hypertrophy in THMs, but that both the RAS and elevation of blood pressure
      contribute to the pathogenesis of renal glomerular sclerosis.

PMID- 9582108
TI  - Exogenous ouabain is accumulated in the adrenals and mimics the kinetics of
      endogenous digitalis-like factor in rats.
AB  - Ouabain has been isolated as an endogenous pathogenetic factor in salt-induced
      hypertension and has been shown to be rich in the adrenals. In this study, organ
      accumulation of orally administered [3H]ouabain was examined in rats. Exogenous
      [3H]ouabain was accumulated in high levels in the adrenals, especially in the
      zona intermedia, and was not metabolized in the rat. Accumulated [3H]ouabain
      mimicked the movement of "endogenous" digitalis-like factor, since 1) the plasma
      [3H]ouabain level decreased in bilaterally adrenalectomized rats, 2) the plasma
      [3H]ouabain level increased accompanied by a decrease in [3H]ouabain content in
      the adrenals in reduced renal mass hypertensive rats, and 3) [3H]ouabain levels
      in plasma and in the adrenals increased in spontaneously hypertensive rats, as
      compared with those in respective control animals. Moreover, the rat diet
      contained a relatively high amount of ouabain-like immunoreactivity (OLI), and
      the ratio of the [3H]ouabain content to OLI in each organ was comparable to that
      of the daily intake of dietary [3H]ouabain to OLI. Furthermore, high 3H
      radioactivities were also observed in the adrenals of rats that ingested
      [3H]digoxin and [3H]digitoxin. These data suggest that exogenous ouabain, related
      cardiotonic glycosides of plant origin, or both accumulate in the adrenals and,
      at least in part, act as "endogenous" digitalis-like factor(s).

PMID- 9582109
TI  - Association of insulin resistance and hyperinsulinemia with disturbed lipid
      metabolism in patients with essential hypertension.
AB  - To clarify the association of insulin resistance and hyperinsulinemia with lipid
      metabolism in patients with essential hypertension (EHT), we used the euglycemic
      hyperinsulinemic glucose clamp technique (GC) and the 75-g oral glucose tolerance
      test (OGTT) to compare the characteristics of glucose and lipid metabolism in
      insulin-resistant patients with essential hypertension (EHT-R) with those in
      insulin-non-resistant patients with essential hypertension (EHT-N) and
      normotensive subjects (NT). Twenty-eight NT and 42 EHT whose body mass index
      (BMI) was less than 28 kg/m2 were studied to eliminate the effects of obesity on
      insulin sensitivity and lipid metabolism. Insulin sensitivity was evaluated by GC
      and expressed as metabolic clearance rate of glucose (M value, mg/m2/min). Mean 
      ISD of the M value in NT (145.0 mg/m2/min) was chosen as the cutoff point for
      insulin resistance. On the basis of this value, 33.3% of the EHT were EHT-R.
      There was no significant difference in age or BMI among the three groups. Blood
      samples were collected before GC to measure levels of total cholesterol (TC),
      triglyceride (TG), free fatty acid (FFA), and HDL cholesterol (HDL-C). EHT-R had
      significantly higher levels of fasting blood sugar, fasting immunoreactive
      insulin, insulin at 120 min (IRI-120), and summation of insulin or blood sugar
      (BS) during the OGTT, as compared with NT and EHT-N. EHT-R also had significantly
      higher FFA and TG than the other two groups, while there was no difference in FFA
      or TG between EHT-N and NT. TC and HDL-C were similar in the three groups. There
      was either a significant negative correlation, or a trend toward negative
      correlation, between M value and FFA (r= -0.50, p < 0.05) or TG (r= -0.24, p <
      0.1). There were significant positive correlations between IRI-120 and FFA
      (r=0.35, p< 0.05) or TG (r=0.29, p< 0.05). There was a positive correlation (r= 
      0.36, p< 0.01) between sigma BS and FFA, while no other significant relation was
      found between sigma BS and serum lipids. In summary, (i) 33.3% of EHT were found
      to be insulin resistant, when insulin resistance was defined as M value < 145.0
      mg/m2/min, i.e., mean -ISD of the M value of NT; (ii) these EHT-R had higher
      levels of BS, insulin, FFA, and TG than did NT and EHT-N; (iii) EHT-N showed no
      difference in the levels of BS, insulin, or lipid, as compared with NT; and (iv)
      the levels of FFA and of TG correlated negatively with insulin sensitivity and
      positively with the insulin level during the OGTT. These results suggest that
      disturbances of glucose and lipid metabolism in EHT may be related to both
      insulin resistance and compensatory hyperinsulinemia, and that EHT-R may have
      more risk factors for arteriosclerotic complications than EHT-N.

PMID- 9582110
TI  - U/Pb zircon geochronology and tempo of the end-permian mass extinction 
AB  - The mass extinction at the end of the Permian was the most profound in the
      history of life. Fundamental to understanding its cause is determining the tempo
      and duration of the extinction. Uranium/lead zircon data from Late Permian and
      Early Triassic rocks from south China place the Permian-Triassic boundary at
      251.4 +/- 0.3 million years ago. Biostratigraphic controls from strata
      intercalated with ash beds below the boundary indicate that the Changhsingian
      pulse of the end-Permian extinction, corresponding to the disappearance of about
      85 percent of marine species, lasted less than 1 million years. At Meishan, a
      negative excursion in delta13C at the boundary had a duration of 165,000 years or
      less, suggesting a catastrophic addition of light carbon.

PMID- 9582111
TI  - Chemical amplification: continuous-flow PCR on a chip.
AB  - A micromachined chemical amplifier was successfully used to perform the
      polymerase chain reaction (PCR) in continuous flow at high speed. The device is
      analogous to an electronic amplifier and relies on the movement of sample through
      thermostated temperature zones on a glass microchip. Input and output of material
      (DNA) is continuous, and amplification is independent of input concentration. A
      20-cycle PCR amplification of a 176-base pair fragment from the DNA gyrase gene
      of Neisseria gonorrhoeae was performed at various flow rates, resulting in total
      reaction times of 90 seconds to 18.7 minutes.

PMID- 9582112
TI  - Predatory dinosaur remains from madagascar: implications for the cretaceous
      biogeography of gondwana 
AB  - Recent discoveries of fossil vertebrates from the Late Cretaceous of Madagascar
      include several specimens of a large theropod dinosaur. One specimen includes a
      nearly complete and exquisitely preserved skull with thickened pneumatic nasals,
      a median frontal horn, and a dorsal projection on the parietals. The new
      materials are assigned to the enigmatic theropod group Abelisauridae on the basis
      of a number of unique features. Fossil remains attributable to abelisaurids are
      restricted to three Gondwanan landmasses: South America, Madagascar, and the
      Indian subcontinent. This distribution is consistent with a revised
      paleogeographic reconstruction that posits prolonged links between these
      landmasses (via Antarctica), perhaps until late in the Late Cretaceous.

PMID- 9582113
TI  - Tracking the evolution of a hydrothermal event plume with a RAFOS neutrally
      buoyant drifter 
AB  - The migration and evolution of a deep ocean hydrothermal event plume were tracked
      with a neutrally buoyant RAFOS float. The float remained entrained in the plume
      for 60 days, and the plume vorticity was calculated directly from the
      anticyclonic motion of the float. Concentrations of suspended particles,
      particulate iron, and dissolved manganese in the plume did not decay
      significantly during the 60 days, which indicates that event plumes would be
      easily detectable a year after formation.

PMID- 9582114
TI  - Earthquakes on dipping faults: the effects of broken symmetry 
AB  - Dynamic simulations of earthquakes on dipping faults show asymmetric near-source
      ground motion caused by the asymmetric geometry of such faults. The ground motion
      from a thrust or reverse fault is larger than that of a normal fault by a factor
      of 2 or more, given identical initial stress magnitudes. The motion of the
      hanging wall is larger than that of the footwall in both thrust (reverse) and
      normal earthquakes. The asymmetry between normal and thrust (reverse) faults
      results from time-dependent normal stress caused by the interaction of the
      earthquake-generated stress field with Earth's free surface. The asymmetry
      between hanging wall and footwall results from the asymmetric mass and geometry
      on the two sides of the fault.

PMID- 9582115
TI  - Percolation of core melts at lower mantle conditions 
AB  - Experiments at high pressure and temperature to determine the dihedral angle of
      core melts in lower mantle phases yielded a value of approximately 71 degrees for
      perovskite-dominated matrices. This angle, although greater than the 60 degrees
      required for completely efficient percolation, is considerably less than the
      angles observed in mineral matrices at upper mantle pressure-temperature
      conditions in experiments. In other words, molten iron alloy can flow much more
      easily in lower mantle mineralogies than in upper mantle mineralogies.
      Accordingly, although segregation of core material by melt percolation is
      probably not feasible in the upper mantle, core formation by percolation may be
      possible in the lower mantle.

PMID- 9582116
TI  - Localized reconnection in the near jovian magnetotail 
AB  - The oppositely directed magnetic field in the jovian magnetic tail is expected
      eventually to reconnect across the current sheet, allowing plasma produced deep
      inside the magnetosphere near Io's orbit to escape in the antisolar direction
      down the tail. The Galileo spacecraft found localized regions of strong northward
      and southward field components beyond about 50 jovian radii in the postmidnight,
      predawn sector of the jovian magnetosphere. These pockets of vertical magnetic
      fields can be stronger than the surrounding magnetotail and magnetodisk fields.
      They may result from episodic reconnection of patches of the near jovian
      magnetotail.

PMID- 9582117
TI  - Ferromagnetism in LaFeO3-LaCrO3 superlattices 
AB  - Ferromagnetic spin order has been realized in the LaCrO3-LaFeO3 superlattices.
      Ferromagnetic coupling between Fe3+ and Cr3+ through oxygen has long been
      expected on the basis of Anderson, Goodenough, and Kanamori rules. Despite many
      studies of Fe-O-Cr-based compounds, random positioning of Fe3+ and Cr3+ ions has
      frustrated the observation of ferromagnetic properties. By creating artificial
      superlattices of Fe3+ and Cr3+ layer along the [111] direction, ferromagnetic
      ordering has been achieved.

PMID- 9582118
TI  - Inducible repair of thymine glycol detected by an ultrasensitive assay for DNA
      damage.
AB  - An ultrasensitive assay for measuring DNA base damage is described that couples
      immunochemical recognition with capillary electrophoresis and laser-induced
      fluorescence detection. The method provides a detection limit of 3 x 10(-21)
      moles, an improvement of four to five orders of magnitude over current methods.
      Induction and repair of thymine glycols were studied in irradiated A549 cells (a
      human lung carcinoma cell line). Exposure of these cells to a low dose of
      radiation (0.25 Gray) 4 hours before a clinically relevant dose (2 Gray) enhanced
      removal of thymine glycols after the higher dose. These data provide evidence for
      an inducible repair response for radiation-induced damage to DNA bases.

PMID- 9582119
TI  - Inhibitory function of p21Cip1/WAF1 in differentiation of primary mouse
      keratinocytes independent of cell cycle control.
AB  - The cyclin-dependent kinase inhibitor p21(Cip1/WAF1) has been implicated as an
      inducer of differentiation. However, although expression of p21 is increased in
      postmitotic cells immediately adjacent to the proliferative compartment, its
      expression is decreased in cells further along the differentiation program.
      Expression of the p21 protein was decreased in terminally differentiated primary
      keratinocytes of mice, and this occurred by a proteasome-dependent pathway.
      Forced expression of p21 in these cells inhibited the expression of markers of
      terminal differentiation at both the protein and messenger RNA levels. These
      inhibitory effects on differentiation were not observed with a carboxyl-terminal
      truncation mutant or with the unrelated cyclin-dependent kinase inhibitor
      p16(INK4a), although all these molecules exerted similar inhibition of cell
      growth. These findings reveal an inhibitory role of p21 in the late stages of
      differentiation that does not result from the effects of p21 on the cell cycle.

PMID- 9582120
TI  - Genetic evaluation of suspected cases of transient HIV-1 infection of infants.
AB  - Detection of human immunodeficiency virus-type 1 (HIV-1) on only one or a few
      occasions in infants born to infected mothers has been interpreted to indicate
      that infection may be transient rather than persistent. Forty-two cases of
      suspected transient HIV-1 viremia among 1562 perinatally exposed seroreverting
      infants and one mother were reanalyzed. HIV-1 env sequences were not found in
      specimens from 20; in specimens from 6, somatic genetic analysis revealed that
      specimens were mistakenly attributed to an infant; and in specimens from 17,
      phylogenetic analysis failed to demonstrate the expected linkage between the
      infant's and the mother's virus. These findings argue that transient HIV-1
      infection, if it exists, will only rarely be satisfactorily documented.

PMID- 9582121
TI  - Large-scale identification, mapping, and genotyping of single-nucleotide
      polymorphisms in the human genome.
AB  - Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in
      the human genome, and they provide powerful tools for a variety of medical
      genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic
      DNA was examined by a combination of gel-based sequencing and high-density
      variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A
      genetic map was constructed showing the location of 2227 of these SNPs. Prototype
      genotyping chips were developed that allow simultaneous genotyping of 500 SNPs.
      The results provide a characterization of human diversity at the nucleotide level
      and demonstrate the feasibility of large-scale identification of human SNPs.

PMID- 9582122
TI  - RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and
      diacylglycerol-binding motifs.
AB  - RasGRP, a guanyl nucleotide-releasing protein for the small guanosine
      triphosphatase Ras, was characterized. Besides the catalytic domain, RasGRP has
      an atypical pair of "EF hands" that bind calcium and a diacylglycerol (DAG)
      binding domain. RasGRP activated Ras and caused transformation in fibroblasts. A
      DAG analog caused sustained activation of Ras-Erk signaling and changes in cell
      morphology. Signaling was associated with partitioning of RasGRP protein into the
      membrane fraction. Sustained ligand-induced signaling and membrane partitioning
      were absent when the DAG-binding domain was deleted. RasGRP is expressed in the
      nervous system, where it may couple changes in DAG and possibly calcium
      concentrations to Ras activation.

PMID- 9582123
TI  - Mutations in the SMAD4/DPC4 gene in juvenile polyposis.
AB  - Familial juvenile polyposis is an autosomal dominant disease characterized by a
      predisposition to hamartomatous polyps and gastrointestinal cancer. Here it is
      shown that a subset of juvenile polyposis families carry germ line mutations in
      the gene SMAD4 (also known as DPC4), located on chromosome 18q21.1, that encodes
      a critical cytoplasmic mediator in the transforming growth factor-beta signaling
      pathway. The mutant SMAD4 proteins are predicted to be truncated at the carboxyl
      terminus and lack sequences required for normal function. These results confirm
      an important role for SMAD4 in the development of gastrointestinal tumors.

PMID- 9582124
TI  - Requirement for Atm in ionizing radiation-induced cell death in the developing
      central nervous system.
AB  - Ataxia telangiectasia (AT) is characterized by progressive neurodegeneration that
      results from mutation of the ATM gene. However, neither the normal function of
      ATM in the nervous system nor the biological basis of the degeneration in AT is
      known. Resistance to apoptosis in the developing central nervous system (CNS) of
      Atm-/- mice was observed after ionizing radiation. This lack of death occurred in
      diverse regions of the CNS, including the cerebellum, which is markedly affected
      in AT. In wild-type, but not Atm-/- mice, up-regulation of p53 coincided with
      cell death, suggesting that Atm-dependent apoptosis in the CNS is mediated by
      p53. Further, p53 null mice showed a similar lack of radiation-induced cell death
      in the developing nervous system. Atm may function at a developmental survival
      checkpoint that serves to eliminate neurons with excessive DNA damage.

PMID- 9582125
TI  - COI1: an Arabidopsis gene required for jasmonate-regulated defense and fertility.
AB  - The coi1 mutation defines an Arabidopsis gene required for response to
      jasmonates, which regulate defense against insects and pathogens, wound healing,
      and pollen fertility. The wild-type allele, COI1, was mapped to a 90-kilobase
      genomic fragment and located by complementation of coi1-1 mutants. The predicted
      amino acid sequence of the COI1 protein contains 16 leucine-rich repeats and an F
      box motif. It has similarity to the F-box proteins Arabidopsis TIR1, human Skp2,
      and yeast Grr1, which appear to function by targeting repressor proteins for
      removal by ubiquitination.

PMID- 9582126
TI  - Calcium channel blockers. The jury is still out on whether they cause heart
      attacks and suicide.

PMID- 9582127
TI  - Toys and games: poorly recognised hearing hazards?. European case ascertainment
      will help to confirm the association.

PMID- 9582128
TI  - Screening for Chlamydia trachomatis. The case for screening is made, but much
      detail remains to be worked out.

PMID- 9582129
TI  - Chronic obstructive pulmonary disease. No longer any justification for
      therapeutic nihilism.

PMID- 9582130
TI  - Breaking down language barriers. The NHS needs to provide accessible interpreting
      services for all.

PMID- 9582131
TI  - Differences in late fetal death rates in association with determinants of small
      for gestational age fetuses: population based cohort study.
AB  - OBJECTIVE: To examine differences in late fetal death rates in association with
      determinants of small for gestational age fetuses. DESIGN: Population based
      cohort study. SUBJECTS: 1 026 249 pregnancies without congenital malformations.
      SETTING: Sweden 1983-92. MAIN OUTCOME MEASURE: Late fetal death rate. RESULTS:
      Depending on underlying determinants late fetal death rates were greatly
      increased in extremely small for gestational age fetuses (range 16 to 45 per
      1000) compared with non-small for gestational age fetuses (1.4 to 4.6). In
      extremely small for gestational age fetuses late fetal death rates were increased
      from 31 per 1000 in mothers aged less than 35 years to 45 per 1000 in older
      mothers, and from 22 per 1000 in women <155 cm in height to 33 per 1000 in women
      >=175 cm tall. Late fetal death rates were also higher in extremely small for
      gestational age fetuses in singleton compared with twin pregnancies and in non
      hypertensive pregnancies compared with pregnancies complicated by severe pre
      eclampsia or other hypertensive disorders. Slightly higher late fetal death rates
      were observed in nulliparous compared with parous women and in non-smokers
      compared with smokers. CONCLUSIONS: Although the risk of late fetal death is
      greatly increased in fetuses that are extremely small for gestational age the
      risk is strongly modified by underlying determinants-for example, there is a
      lower risk of late fetal death in a small for gestational age fetus if the mother
      is of short stature, has a twin pregnancy, or has hypertension.

PMID- 9582132
TI  - Cost effectiveness of community leg ulcer clinics: randomised controlled trial.
AB  - OBJECTIVES: To establish the relative cost effectiveness of community leg ulcer
      clinics that use four layer compression bandaging versus usual care provided by
      district nurses. DESIGN: Randomised controlled trial with 1 year of follow up.
      SETTING: Eight community based research clinics in four trusts in Trent.
      SUBJECTS: 233 patients with venous leg ulcers allocated at random to intervention
      (120) or control (113) group. INTERVENTIONS: Weekly treatment with four layer
      bandaging in a leg ulcer clinic (clinic group) or usual care at home by the
      district nursing service (control group). MAIN OUTCOME MEASURES: Time to complete
      ulcer healing, patient health status, and recurrence of ulcers. Satisfaction with
      care, use of services, and personal costs were also monitored. RESULTS: The
      ulcers of patients in the clinic group tended to heal sooner than those in the
      control group over the whole 12 month follow up (log rank P=0.03). At 12 weeks,
      34% of patients in the clinic group were healed compared with 24% in the control.
      The crude initial healing rate of ulcers in intervention compared with control
      patients was 1.45 (95% confidence interval 1.04 to 2. 03). No significant
      differences were found between the groups in health status. Mean total NHS costs
      were 878.06 pounds per year for the clinic group and 859.34 pounds for the
      control (P=0.89). CONCLUSIONS: Community based leg ulcer clinics with trained
      nurses using four layer bandaging is more effective than traditional home based
      treatment. This benefit is achieved at a small additional cost and could be
      delivered at reduced cost if certain service configurations were used.

PMID- 9582133
TI  - Sex differences in selection of pacemakers: retrospective observational study.
AB  - OBJECTIVE: To evaluate the effect of patients' sex on selection of pacemakers.
      DESIGN: Retrospective univariate and multivariate analysis of a large database.
      SETTING: German central pacemaker register. SUBJECTS: Records collected at the
      register for 1992 and 1993 (n=31 913), covering 64% of all implantations in
      Germany. MAIN OUTCOME MEASURE: Probability of receiving a single chamber, dual
      chamber, or rate responsive pacemaker in relation to sex. RESULTS: Univariate
      analysis showed that women were more likely to receive single chamber pacemakers
      and less likely to receive dual chamber or rate responsive systems than men.
      After demographic and clinical variables were controlled for, women were still
      more likely to receive a single chamber system (atrial pacing: odds ratio 0.89,
      95% confidence interval 0.74 to 1.07; ventricular pacing: 0.85, 0.80 to 0.92) and
      less likely to receive a dual chamber (1.20, 1.12 to 1.30) or a rate responsive
      system (1.26, 1.17 to 1.37) than men. CONCLUSIONS: The data suggest sex
      differences in the selection of a pacemaker system which cannot be explained by
      the underlying cardiac disorder. Further research is needed to evaluate why
      guidelines for implanting pacemakers are not better adhered to.

PMID- 9582134
TI  - Rapid resolution of symptoms and signs of intracerebral haemorrhage: case
      reports.

PMID- 9582135
TI  - Admission for depression among men in Scotland, 1980-95: retrospective study.

PMID- 9582136
TI  - Changing proximal femoral geometry in north east Scotland: an osteometric study.

PMID- 9582137
TI  - Management of hyperlipidaemia after coronary revascularisation: follow up study.

PMID- 9582139
TI  - The new NHS: yes and no 

PMID- 9582138
TI  - Detection of a variant protein in hair: new diagnostic method in Portuguese type
      familial amyloid polyneuropathy.

PMID- 9582140
TI  - Deathbed scenes 

PMID- 9582141
TI  - Out of hours service in Denmark: evaluation five years after reform.
AB  - OBJECTIVE: Five years after its introduction, to evaluate the 1992 reform in the
      out of hours service in Denmark. DESIGN: Comparison of data before and after
      reform. Data were collected from published reports, Danish national health
      statistics, and the Danish trade union for general practitioners. SETTING:
      Denmark. MAIN OUTCOME MEASURES: Number of out of hours services; workload of
      general practitioners; cost of the service; patient satisfaction. RESULTS: Five
      years after the reform, the percentage of telephone consultations had almost
      doubled, to 48%. Consultations in doctors' surgeries were relatively unchanged,
      but home visits were much reduced, to 18%. The percentage of doctors who worked 5
      hours or more out of hours per week dropped from about 70% to about 50%. Overall
      patient satisfaction in 1995 was high (72%). CONCLUSION: The organisation of the
      out of hours service, with a fully trained general practitioner in a telephone
      triage function, is working satisfactorily. Many calls that previously would have
      required home visits are now dealt with by telephone or through consultations.
      The out of hours workload for general practitioners has decreased considerably.

PMID- 9582143
TI  - Psychiatric problem dismissed 

PMID- 9582142
TI  - Shifting of care for diabetes from secondary to primary care, 1990-5: review of
      general practices.

PMID- 9582144
TI  - Helicobacter pylori and gastric diseases.

PMID- 9582145
TI  - Piano player, pathologist, postmortem, postscript 

PMID- 9582146
TI  - Adverse reactions to drugs.

PMID- 9582147
TI  - Ethical debate. Too drunk to care?

PMID- 9582148
TI  - Adjuvant tamoxifen: how long before we know how long?

PMID- 9582149
TI  - BMJ data.

PMID- 9582150
TI  - Facing loss.

PMID- 9582152
TI  - Perspectives in economic evaluation.

PMID- 9582151
TI  - Assessment in primary care: practical issues and possible approaches.

PMID- 9582153
TI  - The depopulation of france 

PMID- 9582154
TI  - Majority view of climate scientists is that global warming is indeed happening.

PMID- 9582155
TI  - PACT data for dispensed drugs linked to NHS numbers are available now.

PMID- 9582156
TI  - There is no such thing as ageing. Ageing has been defined as to grow or make old.

PMID- 9582157
TI  - Can students learn comparable clinical skills in general practice and hospital
      settings?. Students are discriminating consumers of educational experience.

PMID- 9582158
TI  - Compression ultrasonography for diagnosing deep vein thrombosis. One examination
      of whole leg is better than two of selected parts.

PMID- 9582159
TI  - Attitudes to questioning in clinical practice may be changed.

PMID- 9582160
TI  - Time to publication of studies was not affected by whether results were positive.

PMID- 9582162
TI  - Patrick ("Paddy") francis ahern 

PMID- 9582163
TI  - Royal college proposes solutions for medical SRs 

PMID- 9582161
TI  - BMJ has largely met its target for publication time for long papers.

PMID- 9582165
TI  - Outpatients: a ringside view 

PMID- 9582164
TI  - Join the club 

PMID- 9582166
TI  - What makes a healthy website? 

PMID- 9582167
TI  - Non-random reflections on health services research 

PMID- 9582168
TI  - Physician-assisted suicide 

PMID- 9582169
TI  - Some small for gestational age fetuses have higher risk of late fetal death than
      others 

PMID- 9582170
TI  - Case upheld for four layer bandaging for leg ulcers 

PMID- 9582172
TI  - Rates of depression among men in scotland have risen since 1980 

PMID- 9582171
TI  - Women may not be receiving most effective pacemakers 

PMID- 9582174
TI  - More diabetics are being reviewed in general practice but without a proportionate
      decline in secondary care 

PMID- 9582173
TI  - Danish out of hours service is working well 

PMID- 9582176
TI  - Event-related potentials as an index of cognitive function during recovery from
      severe closed head injury.
AB  - OBJECTIVE: To evaluate the utility and neuropsychological correlates of serially
      performed recordings of event-related potentials (ERPs) in patients recovering
      from a severe closed head injury (CHI). DESIGN: Prospective longitudinal study.
      SETTING: Brain injury rehabilitation unit based in a national rehabilitation
      hospital. SUBJECTS: Sixteen patients with severe CHI (significant degree of
      impaired consciousness greater than 24 hours) subclassified into two severity
      groups according to initial Glasgow Coma Scale (GCS) score: those with initial
      GCS score < 9, consistent with a more severe injury; and those with initial GCS
      score > 8, indicating a less severe injury. METHODS: ERPs were elicited using the
      standard auditory P300 "oddball" detection paradigm. ERP recordings were carried
      out three times: 2 months after injury, 1 month later, and 2.5 months or more
      after the initial study. Parameters analyzed included latencies and amplitudes of
      the P3, N2, P2, and N1 components of the ERPs. Correlations between changes in
      these ERP parameters and specific neuropsychological test results were evaluated.
      RESULTS: Initial P3 latencies in the more severely injured group were
      significantly longer (P < .05) than those recorded in the less severely injured
      patients. In subsequent recordings, P3 latency was found to be significantly
      shorter compared with the initial P3 latency, and the difference in P3 latency
      between the two patient groups was no longer statistically significant by the
      time of the third recording. For the group as a whole, P3 latency decreased
      significantly on each repeated recording. N2 latency was found to be
      significantly shorter (P < .05) between the first and third recordings. Cognitive
      performance significantly improved between the first and third recordings. P3
      latency shortening was correlated with improvement in neuropsychological test
      scores for short-term and long-term story recall and for word recall. N2 latency
      shortening was correlated with improvement in the neuropsychological test scores
      for word recall only. CONCLUSION: ERP recordings performed in the subacute stage
      after CHI may assist in evaluating injury severity. Moreover, serially performed
      recordings of P3 latency may be used as a physiologic index of brain activity
      that correlates with recovery from CHI.

PMID- 9582175
TI  - Stability of normal personality traits after traumatic brain injury.
AB  - OBJECTIVE: To test the hypothesis that changes in personality traits are evident
      after traumatic brain injury (TBI) using current models of normal adult
      personality variation. DESIGN: Comparison of inception cohort and control group
      at two measurement occasions. SETTING: A large urban academic medical center.
      PARTICIPANTS: Retrospective personality assessments were obtained from
      significant others of 21 TBI patients within 30 days of injury and at 6-month
      follow-up and from a control group of significant others of 25 persons without
      neurological history twice over a 6-month interval. MAIN OUTCOME MEASURES: Five
      scales-Neuroticism, Extraversion, Openness to Experience, Agreeableness, and
      Conscientiousness-from the revised NEO Personality Inventory (NEO PI-R), Form R,
      and an observer rating scale for retrospective estimates of change (REC).
      RESULTS: Significant score changes were found for only one of the five trait
      domains in the patient sample; controls showed minimal changes overall. Patients'
      Extraversion scores declined to average levels at 6-month follow-up, diminishing
      premorbid differences between patients and controls on this dimension. Subjective
      change estimates made by raters after follow-up reflected perceptions of
      increased neuroticism in patients that were inconsistent with the serial NEO PI-R
      data the raters provided. CONCLUSIONS: The absence of systematic changes in
      personality trait scores among the patients cautions against presuming that such
      changes account for the behavior of TBI patients.

PMID- 9582177
TI  - Distress, depressive symptoms, and depressive disorder among caregivers of
      patients with brain injury.
AB  - OBJECTIVE: To examine the prevalence and correlates of major depression in
      caregivers of individuals with moderate to severe traumatic brain injuries.
      DESIGN: Repeated-measures design involving structured diagnostic interview and
      self-report of psychological distress administered on two occasions separated by
      6 months. SETTING: Three acute care rehabilitation hospitals. SUBJECTS: Fifty
      nine caregivers (39 mothers and 20 spouses) of individuals with moderate to
      severe brain injuries recruited from previous inpatient rosters. All caregivers
      were currently residing with the person with traumatic brain injury. MAIN OUTCOME
      MEASURE: The Diagnostic Interview Schedule-Revised [DIS-R] was utilized to assess
      depression. The Symptom Checklist 90-Revised (SCL 90-R) measured general
      psychological distress. RESULTS: Forty-seven percent of caregivers initially met
      diagnostic criteria for depression, and 43% met criteria 6 months later. Nearly
      two thirds of those who were initially depressed continued to be depressed 6
      months later, and 17% of those who were not depressed initially subsequently met
      criteria for depression. The best predictor of depression was a previous (pre
      brain injury) depressive episode. Neither time since injury nor injury severity
      predicted diagnostic status, and spouses were no more likely to be depressed than
      were mothers. The SCL 90-R, including its depression scale, showed high
      specificity but low sensitivity in predicting diagnostic status. CONCLUSIONS: The
      prevalence of major depression is high in caregivers of individuals with brain
      injuries. Because depression may interfere with the capacity to provide care and
      contribute to the rehabilitation process, it is important for clinicians to
      carefully assess both the current and preaccident affective status of primary
      caregivers.

PMID- 9582178
TI  - Use of elaborative encoding to facilitate verbal learning after adolescent
      traumatic brain injury.
AB  - OBJECTIVE: To investigate the effectiveness of elaborative encoding in learning
      and remembering word definitions after traumatic brain injury (TBI). DESIGN: Two
      case studies. SETTING: University outpatient clinic. PARTICIPANTS: Two
      adolescents with severe memory impairments after TBI who needed specific
      vocabulary for school. INTERVENTIONS: A series of individual speech-language
      therapy sessions incorporating clinician- and subject-generated strategies to
      facilitate elaborative encoding. Target words were based on school requirements
      and pretreatment test results and were assigned randomly to treatment or control
      groups. MAIN OUTCOME MEASURE: Accuracy of free-recalled definitions at the
      conclusion of therapy and after 1 month with no therapy. RESULTS: Significant
      improvement in expressed word knowledge at the conclusion of therapy, with
      improvement on treated words maintained at 1 month for both subjects.
      CONCLUSIONS: Elaborative encoding was an effective tool for teaching specific
      information required for school. Patterns of response differed substantially from
      those of normally developing children. Generalization to classroom use was
      planned for and should be measured in future research.

PMID- 9582179
TI  - NeuroSPECT findings in patients with posttraumatic anosmia: a quantitative
      analysis.
AB  - OBJECTIVE: To investigate quantitative neuroSPECT findings, particularly from
      orbital frontal cortex, in patients rendered totally anosmic from head injury.
      SETTING: Veterans Administration (VA) Medical Center. SUBJECTS: Eighteen patients
      with head injury resulting in severe anosmia and five normal controls. All 18
      patients had sustained their head injuries at least 5 years prior to involvement
      in the study. MEASURES: Quantitative neuroSPECT (count density) from sagittal
      regions of interest (ROIs) ranging circumferentially from orbital frontal cortex
      to occipital pole. RESULTS: Quantitative evaluation of neuroSPECT findings for
      anosmic patients as a group showed substantial orbital frontal hypoperfusion
      compared with controls, with 67% of individual anosmic patients showing orbital
      frontal hypoperfusion at a level two or more standard deviations below that of
      the worst control subject. By contrast, there were no between-group differences
      for five other ROIs (inferior frontal pole, superior frontal pole, posterior
      superior frontal lobe, the parasagittal region, and occipital pole), and
      individual abnormalities were infrequent in these areas. In addition, orbital
      frontal count was significantly correlated with ratings of outcome, the only ROI
      to have such a relationship. CONCLUSIONS: Findings strongly suggest that
      posttraumatic anosmia and the neuropsychological deficits typically associated
      with posttraumatic anosmia are closely and specifically associated with
      hypoperfusion in orbital frontal cortex. The results also underscore the
      importance of posttraumatic anosmia as a clinical sign of orbital frontal damage,
      which is particularly important in patients with mild head injury who have normal
      computed tomography and magnetic resonance imaging scans.

PMID- 9582180
TI  - Recovery in pediatric brain injury: is psychostimulant medication beneficial?
AB  - OBJECTIVE: To assess the effects of methylphenidate on attention, memory,
      behavior, processing speed, and psychomotor skills of children with closed head
      injuries. DESIGN: Double-blind, placebo-controlled, crossover design. SETTING: An
      outpatient facility of a children's hospital medical center. PATIENTS: Ten
      pediatric subjects identified through chart review. Subjects met baseline scores
      for hyperactivity (Conner's Hyperactivity Index greater than or equal to 60) and
      intellectual functioning (Verbal Intelligence Quotient greather than or equal to
      70) and achieved minimal scores on two psychometric tests. All subjects evidenced
      head injury by focal lesions on computed tomography scan and/or sequelae reported
      at the time of injury. Severity of injury ranged from mild to severe. All
      subjects were medically stable at the time of testing. Mean time post injury was
      2 years, 8 months. INTERVENTION: Administration of methylphenidate and placebo.
      MAIN OUTCOME MEASURES: Percentage change in scores was calculated to assess
      differences between baseline and end of methylphenidate/placebo trials. RESULTS:
      No significant differences between methylphenidate and placebo on measures
      assessing behavior, attention, memory, and processing speed. CONCLUSIONS: The
      results of the study call into question the effectiveness of methylphenidate in
      the pediatric head injury population.

PMID- 9582182
TI  - Does the SCL 90-R obsessive-compulsive dimension identify cognitive impairments?
AB  - OBJECTIVE: To investigate the relevance of the Symptom Checklist 90-R Obsessive
      Compulsive subscale to cognition in individuals with brain tumor. DESIGN: A
      prospective study of patients assessed with a neuropsychological test battery.
      SETTING: A university medical center. PATIENTS: Nineteen adults with biopsy
      confirmed diagnoses of malignant brain tumors were assessed prior to aggressive
      chemotherapy. MAIN OUTCOME MEASURES: Included in the assessment were the Mattis
      Dementia Rating Scale, California Verbal Learning Test, Trail Making Test B,
      Symptom Checklist 90-R, Mood Assessment Scale, Beck Anxiety Inventory, and
      Chronic Illness Problem Inventory. RESULTS: The SCL 90-R Obsessive-Compulsive
      subscale was not related to objective measures of attention, verbal memory, or
      age. It was related significantly to symptoms of depression (r = .81, P < .005),
      anxiety (r = .66, P < .005), and subjective complaints of memory problems (r =
      .75, P < .005). Multivariate analyses indicated that reported symptoms of
      depression contributed 66% of the variance in predicting SCL 90-R Obsessive
      Compulsive Scores, whereas symptoms of anxiety contributed an additional 6% (P <
      .0001). CONCLUSIONS: Our data suggest that the SCL 90-R is best viewed as an
      indicator of unidimensional emotional distress and somatic effects of structural
      brain injury.

PMID- 9582181
TI  - Performance of administrators, professionals, and paraprofessionals during
      community-based brain injury rehabilitation training.
AB  - OBJECTIVE: Two related studies that evaluated the impact of a continuing
      education program about community-based rehabilitation on the performance of
      administrators, professionals, and paraprofessionals are presented. One study
      contained a second part that examined whether differences between pre-course test
      performance and post-course test performance might be accounted for by practice
      effects. DESIGN: Factorial mixed model designs. SETTING: University classroom.
      PARTICIPANTS: Three hundred and eight professionals, administrators, and
      paraprofessionals from a variety of community-based rehabilitation programs.
      INTERVENTION: The 4-day graduate-level course focused on three content areas:
      brain and behavior relationships, behavioral and cognitive intervention
      strategies, and a rehabilitation philosophy that emphasizes individual client
      rights. MAIN OUTCOME MEASURE: An examination completed before and immediately
      after taking the course. RESULTS: Professionals and administrators perform better
      than paraprofessionals when tested at the beginning and end of the training.
      However, the absolute differences among these groups were not substantial. In
      addition, the rate of learning course content was the same for administrators,
      paraprofessionals, and professionals. CONCLUSIONS: The results support the
      usefulness of training for all levels of staff and suggest that all levels of
      staff benefit in an equal fashion.

PMID- 9582183
TI  - Statement on the rapid release of genomic DNA sequence.

PMID- 9582184
TI  - A "quality-first" credo for the Human Genome Project.

PMID- 9582185
TI  - Targeting transposition: at home in the genome.

PMID- 9582186
TI  - Trapping human ribosomal protein genes.

PMID- 9582187
TI  - WebWise: guide to McDermott Center for Human Growth and Development at University
      of Texas Southwest web site.

PMID- 9582188
TI  - Genetic studies in the sleep disorder narcolepsy.
AB  - Narcolepsy is a chronic neurologic disorder characterized by excessive daytime
      sleepiness and abnormal manifestations of REM sleep including cataplexy, sleep
      paralysis, and hypnagogic hallucinations. Narcolepsy is both a significant
      medical problem and a unique disease model for the study of sleep. Research in
      human narcolepsy has led to the identification of specific HLA alleles (DQB1*0602
      and DQA1*0102) that predispose to the disorder. This has suggested the
      possibility that narcolepsy may be an autoimmune disorder, a hypothesis that has
      not been confirmed to date. Genetic factors other than HLA are also likely to be
      involved. In a canine model of narcolepsy, the disorder is transmitted as a non
      MHC single autosomal recessive trait with full penetrance (canarc-1). A tightly
      linked marker for canarc-1 has been identified, and positional cloning studies
      are under way to isolate canarc-1 from a newly developed canine genomic BAC
      library. The molecular cloning of this gene may lead to a better understanding of
      sleep mechanisms, as has been the case for circadian rhythms following the
      cloning of frq, per, and Clock.

PMID- 9582189
TI  - Simultaneous genotyping and species identification using hybridization pattern
      recognition analysis of generic Mycobacterium DNA arrays.
AB  - High-density oligonucleotide arrays can be used to rapidly examine large amounts
      of DNA sequence in a high throughput manner. An array designed to determine the
      specific nucleotide sequence of 705 bp of the rpoB gene of Mycobacterium
      tuberculosis accurately detected rifampin resistance associated with mutations of
      44 clinical isolates of M. tuberculosis. The nucleotide sequence diversity in 121
      Mycobacterial isolates (comprised of 10 species) was examined by both
      conventional dideoxynucleotide sequencing of the rpoB and 16S genes and by
      analysis of the rpoB oligonucleotide array hybridization patterns. Species
      identification for each of the isolates was similar irrespective of whether 16S
      sequence, rpoB sequence, or the pattern of rpoB hybridization was used. However,
      for several species, the number of alleles in the 16S and rpoB gene sequences
      provided discordant estimates of the genetic diversity within a species. In
      addition to confirming the array's intended utility for sequencing the region of
      M. tuberculosis that confers rifampin resistance, this work demonstrates that
      this array can identify the species of nontuberculous Mycobacteria. This
      demonstrates the general point that DNA microarrays that sequence important
      genomic regions (such as drug resistance or pathogenicity islands) can
      simultaneously identify species and provide some insight into the organism's
      population structure.

PMID- 9582190
TI  - Two large families of chemoreceptor genes in the nematodes Caenorhabditis elegans
      and Caenorhabditis briggsae reveal extensive gene duplication, diversification,
      movement, and intron loss.
AB  - The str family of genes encoding seven-transmembrane G-protein-coupled or
      serpentine receptors related to the ODR-10 diacetyl chemoreceptor is very large,
      with at least 197 members in the Caenorhabditis elegans genome. The closely
      related stl family has 43 genes, and both families are distantly related to the
      srd family with 55 genes. Analysis of the structures of these genes indicates
      that a third of them are clearly or likely pseudogenes. Preliminary surveys of
      other candidate chemoreceptor families indicates that as many as 800 genes and
      pseudogenes or 6% of the genome might encode 550 functional chemoreceptors
      constituting 4% of the C. elegans protein complement. Phylogenetic analyses of
      the str and stl families, and comparisons with a few orthologs in Caenorhabditis
      briggsae, reveal ongoing processes of gene duplication, diversification, and
      movement. The reconstructed ancestral gene structures for these two families have
      eight introns each, four of which are homologous. Mapping of intron distributions
      on the phylogenetic tree reveals that each intron has been lost many times
      independently. Most of these introns were lost individually, which might best be
      explained by precise in-frame deletions involving nonhomologous recombination
      between short direct repeats at their termini. [Alignment of the putatively
      functional proteins in the str and stl families is available from Pfam
      (http://genome. wustl.edu/Pfam); alignments of all translations are available at
      http://cshl.org/gr; alignments of the genes are available from the author at
      hughrobe@uiuc.edu]

PMID- 9582191
TI  - Transposable elements and genome organization: a comprehensive survey of
      retrotransposons revealed by the complete Saccharomyces cerevisiae genome
      sequence.
AB  - We conducted a genome-wide survey of Saccharomyces cerevisiae retrotransposons
      and identified a total of 331 insertions, including 217 Ty1, 34 Ty2, 41 Ty3, 32
      Ty4, and 7 Ty5 elements. Eighty-five percent of insertions were solo long
      terminal repeats (LTRs) or LTR fragments. Overall, retrotransposon sequences
      constitute >377 kb or 3.1% of the genome. Independent evolution of
      retrotransposon sequences was evidenced by the identification of a single-base
      pair insertion/deletion that distinguishes the highly similar Ty1 and Ty2 LTRs
      and the identification of a distinct Ty1 subfamily (Ty1'). Whereas Ty1, Ty2, and
      Ty5 LTRs displayed a broad range of sequence diversity (typically ranging from
      70%-99% identity), Ty3 and Ty4 LTRs were highly similar within each element
      family (most sharing >96% nucleotide identity). Therefore, Ty3 and Ty4 may be
      more recent additions to the S. cerevisiae genome and perhaps entered through
      horizontal transfer or past polyploidization events. Distribution of Ty elements
      is distinctly nonrandom: 90% of Ty1, 82% of Ty2, 95% of Ty3, and 88% of Ty4
      insertions were found within 750 bases of tRNA genes or other genes transcribed
      by RNA polymerase III. tRNA genes are the principle determinant of
      retrotransposon distribution, and there is, on average, 1.2 insertions per tRNA
      gene. Evidence for recombination was found near many Ty elements, particularly
      those not associated with tRNA gene targets. For these insertions, 5'- and 3'
      flanking sequences were often duplicated and rearranged among multiple
      chromosomes, indicating that recombination between retrotransposons can influence
      genome organization. S. cerevisiae offers the first opportunity to view
      organizational and evolutionary trends among retrotransposons at the genome
      level, and we hope our compiled data will serve as a starting point for further
      investigation and for comparison to other, more complex genomes.

PMID- 9582192
TI  - Dispersed repetitive DNA has spread to new genomes since polyploid formation in
      cotton.
AB  - Polyploid formation has played a major role in the evolution of many plant and
      animal genomes; however, surprisingly little is known regarding the subsequent
      evolution of DNA sequences that become newly united in a common nucleus. Of
      particular interest is the repetitive DNA fraction, which accounts for most
      nuclear DNA in higher plants and animals and which can be remarkably different,
      even in closely related taxa. In one recently formed polyploid, cotton (Gossypium
      barbadense L.; AD genome), 83 non-cross-hybridizing DNA clones contain dispersed
      repeats that are estimated to comprise about 24% of the nuclear DNA. Among these,
      64 (77%) are largely restricted to diploid taxa containing the larger A genome
      and collectively account for about half of the difference in DNA content between
      Old World (A) and New World (D) diploid ancestors of cultivated AD tetraploid
      cotton. In tetraploid cotton, FISH analysis showed that some A-genome dispersed
      repeats appear to have spread to D-genome chromosomes. Such spread may also
      account for the finding that one, and only one, D-genome diploid cotton,
      Gossypium gossypioides, contains moderate levels of (otherwise) A-genome-specific
      repeats in addition to normal levels of D-genome repeats. The discovery of A
      genome repeats in G. gossypioides adds genome-wide support to a suggestion
      previously based on evidence from only a single genetic locus that this species
      may be either the closest living descendant of the New World cotton ancestor, or
      an adulterated relic of polyploid formation. Spread of dispersed repeats in the
      early stages of polyploid formation may provide a tag to identify diploid
      progenitors of a polyploid. Although most repetitive clones do not correspond to
      known DNA sequences, 4 correspond to known transposons, most contain internal
      subrepeats, and at least 12 (including 2 of the possible transposons) hybridize
      to mRNAs expressed at readily discernible levels in cotton seedlings, implicating
      transposition as one possible mechanism of spread. Integration of molecular,
      phylogenetic, and cytogenetic analysis of dispersed repetitive DNA may shed new
      light on evolution of other polyploid genomes, as well as providing valuable
      landmarks for many aspects of genome analysis.

PMID- 9582193
TI  - Estimation of distances and map construction using radiation hybrids.
AB  - A method of estimating distances between pairs of genetic markers is described
      that directly uses their observed joint frequency distribution in a panel of
      radiation hybrids (RHs). The distance measure is based on the strength of
      association between marker pairs, which is high for close markers and decays with
      distance. These distances are then submitted to a previous method that generates
      linear coordinates for the markers directly from the intermarker distance matrix.
      This method of map building from RH data is simpler than others, because it uses
      only the observed joint frequency distributions of markers in the panel, and does
      not attempt to model unobserved quantities such as the retention of different
      sized fragments that contain the markers. It also incorporates directly the
      observed variation in retention of different markers, without needing a model for
      differential fragment retention dependent on chromosomal location, which is
      generally not known. Only small, precise distances are used in map construction,
      thereby reducing any effects of different fragment retention frequencies and
      local variations in X-ray sensitivity. The method is tested by simulation, and
      known marker distances and locations are successfully recovered from RH raw data.
      The method is also applied to publicly available data sets related to the recent
      transcript map of the human genome.

PMID- 9582194
TI  - A map of 75 human ribosomal protein genes.
AB  - We mapped 75 genes that collectively encode >90% of the proteins found in human
      ribosomes. Because localization of ribosomal protein genes (rp genes) is
      complicated by the existence of processed pseudogenes, multiple strategies were
      devised to identify PCR-detectable sequence-tagged sites (STSs) at introns. In
      some cases we exploited specific, pre-existing information about the intron/exon
      structure of a given human rp gene or its homolog in another vertebrate. When
      such information was unavailable, selection of PCR primer pairs was guided by
      general insights gleaned from analysis of all mammalian rp genes whose
      intron/exon structures have been published. For many genes, PCR amplification of
      introns was facilitated by use of YAC pool DNAs rather than total human genomic
      DNA as templates. We then assigned the rp gene STSs to individual human
      chromosomes by typing human-rodent hybrid cell lines. The genes were placed more
      precisely on the physical map of the human genome by typing of radiation hybrids
      or screening YAC libraries. Fifty-one previously unmapped rp genes were
      localized, and 24 previously reported rp gene localizations were confirmed,
      refined, or corrected. Though functionally related and coordinately expressed,
      the 75 mapped genes are widely dispersed: Both sex chromosomes and at least 20 of
      the 22 autosomes carry one or more rp genes. Chromosome 19, known to have a high
      gene density, contains an unusually large number of rp genes (12). This map
      provides a foundation for the study of the possible roles of ribosomal protein
      deficiencies in chromosomal and Mendelian disorders.

PMID- 9582195
TI  - Alternate polyadenylation in human mRNAs: a large-scale analysis by EST
      clustering.
AB  - Alternate polyadenylation is an important post-transcriptional regulatory process
      now open to large-scale analysis by use of cDNA databases. We clustered 164,000
      expressed sequence tags (ESTs) into approximately 15,000 groups and aligned each
      group to a putative mRNA 3' end. By use of stringent criteria to discard
      artifactual mRNA extremities, clear evidence for alternate polyadenylation was
      obtained in 189 of the 1000 EST clusters studied. A number of previously
      unreported polyadenylation sites were identified, together with possible
      instances of tissue-specific differential polyadenylation. This study
      demonstrates that, besides quantitative aspects of gene expression, the
      distribution of alternate mRNA forms can be analyzed through EST sampling.

PMID- 9582196
TI  - A high-resolution microsatellite map of the mouse genome.
AB  - The European Collaborative Interspecific Backcross (EUCIB) resource was
      constructed for the purposes of high-resolution genetic mapping of the mouse
      genome (). The large Mus spretus/C57BL/6 backcross of 982 progeny has a genetic
      resolution of 0.3 cM at the 95% confidence level ( approximately 500 kb in the
      mouse genome). We have used the EUCIB mapping resource to develop a genome-wide
      high-resolution genetic map incorporating 3368 microsatellites. The
      microsatellites are distributed among 2302 genetically separated bins with 1.46
      markers per bin on average. Average bin separation is 0.61 cM. This high
      resolution genetic map will aid the construction of a robust physical map of the
      mouse genome.

PMID- 9582197
TI  - A pneumatic device for rapid loading of DNA sequencing gels.
AB  - This work describes the design and construction of a device that facilitates the
      loading of DNA samples onto polyacrylamide gels for detection in the Perkin
      Elmer/Applied Biosystems (PE/ABI) 373 and 377 DNA sequencing instruments. The
      device is mounted onto the existing gel cassettes and makes the process of
      loading high-density gels less cumbersome while the associated time and errors
      are reduced. The principle of operation includes the simultaneous transfer of the
      entire batch of samples, in which a spring-loaded air cylinder generates positive
      pressure and flexible silica capillaries transfer the samples. A retractable
      capillary array carrier allows the delivery ends of the capillaries to be held up
      clear of the gel during loader attachment on the gel plates, while enabling their
      insertion in the gel wells once the device is securely mounted. Gel-loading
      devices capable of simultaneously transferring 72 samples onto the PE/ABI 373 and
      377 are currently being used in our production sequencing groups while a 96
      sample transfer prototype undergoes testing.

PMID- 9582198
TI  - A homogeneous, ligase-mediated DNA diagnostic test.
AB  - Single-nucleotide variations are the most widely distributed genetic markers in
      the human genome. A subset of these variations, the substitution mutations, are
      responsible for most genetic disorders. As single nucleotide polymorphism (SNP)
      markers are being developed for molecular diagnosis of genetic disorders and
      large-scale population studies for genetic analysis of complex traits, a simple,
      sensitive, and specific test for single nucleotide changes is highly desirable.
      In this report we describe the development of a homogeneous DNA detection method
      that requires no further manipulations after the initial reaction is set up. This
      assay, named dye-labeled oligonucleotide ligation (DOL), combines the PCR and the
      oligonucleotide ligation reaction in a two-stage thermal cycling sequence with
      fluorescence resonance energy transfer (FRET) detection monitored in real time.
      Because FRET occurs only when the donor and acceptor dyes are in close proximity,
      one can infer the genotype or mutational status of a DNA sample by monitoring the
      specific ligation of dye-labeled oligonucleotide probes. We have successfully
      applied the DOL assay to genotype 10 SNPs or mutations. By designing the PCR
      primers and ligation probes in a consistent manner, multiple assays can be done
      under the same thermal cycling conditions. The standardized design and execution
      of the DOL assay means that it can be automated for high-throughput genotyping in
      large-scale population studies.

PMID- 9582199
TI  - Sequencing multimegabase-template DNA with BigDye terminator chemistry.
AB  - Using the recently introduced BigDye terminators, large-template DNA can be
      directly sequenced with custom primers on automated instruments. Cycle sequencing
      conditions are presented to sequence DNA samples isolated from a number of
      microbial genomes including 750-kb Ureaplasma urealyticum, 1.2-Mb Mycoplasma
      fermentans, 2.3-Mb Streptococcus pneumoniae, and 4.6-Mb Escherichia coli. Average
      read lengths of >700 bp from unique primer annealing sites are often sufficient
      to fill final gaps in microbial genome sequencing projects without additional
      manipulations of template DNA. The technique can also be applied to sequence
      targeted regions, thereby bypassing tedious subcloning steps.

PMID- 9582201
TI  - Role of monkey cerebellar nuclei in skill for sequential movement.
AB  - To examine whether the cerebellum is involved in learning and memory of
      visuomotor sequences, we trained two monkeys on a sequential button press task
      and inactivated different portions of the cerebellar nuclei by injecting a small
      amount of muscimol (gamma-aminobutyric acid agonist). Before the injection
      experiments started, the monkeys had learned a set of sequences (n = 21 and 12)
      extensively. After each injection, we had the monkeys perform the learned
      sequences and, in addition, learn new sequences. We found deficits in
      learning/memory by the injections into the dorsal and central part of the dentate
      nucleus. The number of errors increased significantly for the learned sequences
      but not for the new sequences. This effect was present only when the hand
      ipsilateral to the muscimol injection was used. Consistent with this result,
      anticipatory saccades, the occurrence of which is correlated closely with motor
      skill, also became less frequent particularly when the ipsilateral hand was used.
      No effect on learning/memory was observed after injections into the ventral or
      lateral parts of the dentate nucleus, interpositus nucleus, or fastigial nucleus.
      In contrast, hand movements became slower after ipsilateral injections at all of
      the injection sites. These results suggest that, among the cerebellar nuclei, the
      dentate nucleus, especially its dorsal and central regions, is related to the
      storage and/or retrieval of long-term memory for motor skill.

PMID- 9582200
TI  - Short-insert libraries as a method of problem solving in genome sequencing.
AB  - As the Human Genome Project moves into its sequencing phase, a serious problem
      has arisen. The same problem has been increasingly vexing in the closing phase of
      the Caenorhabditis elegans project. The difficulty lies in sequencing efficiently
      through certain regions in which the templates (DNA substrates for the sequencing
      process) form complex folded secondary structures that are inaccessible to the
      enzymes. The solution, however, is simply to break them up. Specifically, the
      offending fragments are sonicated heavily and recloned, as much smaller
      fragments, into pUC vector. The sequences obtained from the resulting library can
      subsequently be assembled, free from the effects of secondary structure, to
      produce high-quality, complete sequence. Because of the success and simplicity of
      this procedure, we have begun to use it for the sequencing of all regions in
      which standard primer walking has been at all difficult.

PMID- 9582202
TI  - Basilar membrane vibration in the gerbil hemicochlea.
AB  - Excised gerbil cochleae were cut along the mid-modiolar plane (hemicochlea).
      Along one-half turn of this preparation, fluorescent microbeads were placed on
      the basilar membrane (BM). The BM was vibrated with click stimuli (50 micros)
      produced mechanically by a piezo pusher. The stimulus delivery probe could be
      positioned either more apical or more basal from the beads. Vibration patterns
      were measured with a wide bandwidth photomultiplier from the movements of the
      beads. When the probe was positioned more basal, the responses to click stimuli
      were brief, damped sinusoids. According to the fast Fourier transforms (FFTs) of
      the averaged time wave forms, the best frequency between successive beads
      decreased toward the apex (0.8 octave/mm). Sharpness of tuning of the normalized
      FFT spectra (NQ10dB) on average was 1.5. Response amplitude at a fixed input
      level, measured at different beads away from the stimulation site, dropped
      exponentially (58 dB/mm). In addition, for each individual bead, amplitude
      dropped linearly with decreasing stimulus intensity. In experiments where the
      stimulating probe was placed more apical, two major properties were observed:
      first, beads revealed only the spectral components present in the motion of the
      probe. Second, magnitude reduction of the displacement of the cochlear partition
      was greater, on average 155 dB/mm, indicating a lack of significant propagation
      in the reverse direction.

PMID- 9582203
TI  - Representation of wrist joint kinematics by the ensemble of muscle spindles from
      synergistic muscles.
AB  - Proprioceptive information about movement is transmitted to the central nervous
      system by a variety of receptor types, which are widely distributed among the
      muscles, joints, and skin. Muscle spindles are known to be an important and
      reliable source of information for the perception of movement kinematics.
      Previous studies that focused on the characteristics of single muscle spindle
      firing patterns have left the impression that each receptor fires in relation to
      a number of kinematic variables, leaving the following question unanswered: what
      role is played by the ensemble of muscle spindles within the same muscle or
      within synergistic muscles? The study described in this paper addressed whether
      the perception of joint position and velocity is based on the net input of muscle
      spindles residing in all synergistic muscles crossing a joint. Normal human
      adults performed a motor coordination task that required perception of joint
      velocity and dynamic position at the wrist. The task was to open the left hand
      briskly as the right wrist was passively rotated in the flexion direction through
      a prescribed target angle. In randomly occurring trials, the tendons to three
      muscles [extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), and
      extensor digitorum (ED)] were vibrated either individually or in different
      combinations during the performance of the motor task. Tendon vibration is known
      to distort muscle spindle firing patterns, and consequently, kinesthesia. By
      comparing performance errors with and without tendon vibration, the relative
      influences of muscle spindles residing in ECR, ECU, and ED were quantified.
      Vibration of the individual ECR, ECU, or ED tendons produced systematic
      undershoot errors in performance, consistent with the misperception of wrist
      velocity and dynamic position. Performance errors were larger when combinations
      of, rather than individual, muscle tendons were vibrated. The error resulting
      from simultaneous vibration of ECR and ECU was roughly equal to the sum of the
      errors produced by vibration of the individual tendons. These effects of
      vibrating synergistic tendons at the wrist suggest that kinesthesia is derived
      from the integrated input of muscle spindles from all synergistic muscles.

PMID- 9582204
TI  - Development of spontaneous synaptic transmission in the rat spinal cord.
AB  - Dorsal root afferents form synaptic connections on motoneurons a few days after
      motoneuron clustering in the rat lumbar spinal cord, but frequent spontaneous
      synaptic potentials are detected only after birth. To increase our understanding
      of the mechanisms underlying the differentiation of synaptic transmission, we
      examined the developmental changes in properties of spontaneous synaptic
      transmission at early stages of synapse formation. Spontaneous postsynaptic
      currents (PSCs) and tetrodotoxin (TTX)-resistant miniature PSCs (mPSCs) were
      measured in spinal motoneurons of embryonic and postnatal rats using whole cell
      patch-clamp recordings. Spontaneous PSC frequencies were higher than mPSC
      frequencies in both embryonic and postnatal motoneurons, suggesting that even at
      embryonic stages, when action-potential firing rate was low, presynaptic action
      potentials played an important role in triggering spontaneous PSCs. After birth,
      the twofold increase in spontaneous PSC frequency was attributed to an increase
      in action-potential-independent quantal release rather than to a higher rate of
      action-potential firing. In embryonic motoneurons, the fluctuations in peak
      amplitude of spontaneous PSCs were normally distributed around single peaks with
      modal values similar to those of mPSCs. These data indicated that early in
      synapse differentiation spontaneous PSCs were primarily composed of currents
      generated by quantal release. After birth, mean mPSC amplitude increased by 50%
      but mean quantal current amplitude did not change. Synchronous, multiquantal
      release was apparent in postnatal motoneurons only in high-K+ extracellular
      solution. Comparison of the properties of miniature excitatory and inhibitory
      postsynaptic currents (mEPSCs and mIPSCs) demonstrated that mean mEPSC frequency
      was higher than mIPSC frequency, suggesting that either excitatory synapses
      outnumbered inhibitory synapses or that the probability of excitatory transmitter
      release was higher than the release of inhibitory neurotransmitters. The finding
      that mIPSC duration was several-fold longer than mEPSC duration implied that
      despite their lower frequency, inhibitory currents could modulate motoneuron
      synaptic integration by shunting incoming excitatory inputs for prolonged time
      intervals.

PMID- 9582205
TI  - Activity-dependent regulation of [Ca2+]i in avian cochlear nucleus neurons: roles
      of protein kinases A and C and relation to cell death.
AB  - Neurons of the cochlear nucleus, nucleus magnocellularis (NM), of young chicks
      require excitatory afferent input from the eighth nerve for maintenance and
      survival. One of the earliest changes seen in NM neurons after deafferentation is
      an increase in intracellular calcium concentration ([Ca2+]i). This increase in
      [Ca2+]i is due to loss of activation of metabotropic glutamate receptors (mGluR)
      that activate second-messenger cascades involved in [Ca2+]i regulation. Because
      mGluRs are known to act via the phospholipase C and adenylate cyclase signal
      transduction pathways, the goal of this study was to determine the roles of
      protein kinases A (PKA) and C (PKC) activities in the regulation of NM neuron
      [Ca2+]i by eighth nerve stimulation. Additionally, we sought to determine the
      relationship between increased [Ca2+]i and cell death as measured by propidium
      iodide incorporation. [Ca2+]i of individual NM neurons in brain stem slices was
      monitored using fura-2 ratiometric fluorescence imaging. NM field potentials were
      monitored in experiments in which the eighth nerve was stimulated. Five hertz
      orthodromic stimulation maintained NM neuron [Ca2+]i at approximately 110 nM for
      180 min. In the absence of stimulation, NM neuron [Ca2+]i increased steadily to a
      mean of 265 nM by 120 min. This increase was attenuated by superfusion of PKC
      activators phorbol-12,13-myristate acetate (100 nM) or dioctanoylglycerol (50
      microM) and by activators of PKA: 1 mM 8-bromoadenosine-3',5'-cyclophosphate
      sodium (8-Br-cAMP), 50 microM forskolin or 100 microM Sp-adenosine 3',5'-cyclic
      monophosphothioate triethylamine. Inhibition of PKA (100 microM Rp-cAMPS) or PKC
      (50 nM bisindolymaleimide or 10 microM U73122) during continuous orthodromic
      stimulation resulted in an increase in NM neuron [Ca2+]i that exceeded 170 and
      180 nM, respectively, by 120 min. Nonspecific kinase inhibition with 1 microM
      staurosporine during stimulation resulted in an [Ca2+]i increase that was greater
      in magnitude than that seen with either PKA or PKC inhibition alone, equal to
      that seen in the absence of stimulation, but much smaller than that seen with
      inhibition of mGluRs. In addition, manipulations that resulted in a [Ca2+]i
      increase >/=250 nM resulted in an increase in number and percentage of propidium
      iodide-labeled NM neurons. These results suggest that eighth nerve activity
      maintains [Ca2+]i of NM neurons at physiological levels in part via mGluR
      mediated activation of PKA and PKC and that increases in [Ca2+]i due to activity
      deprivation or interruption of the PKA and PKC [Ca2+]i regulatory mechanisms are
      predictive of subsequent cell death.

PMID- 9582206
TI  - GABAergic disinhibition affects responses of bat inferior collicular neurons to
      temporally patterned sound pulses.
AB  - Using the big brown bat, Eptesicus fuscus, as a model mammalian auditory system,
      we studied the effect of GABAergic disinhibition by bicuculline on the responses
      of inferior collicular (IC) neurons to temporally patterned trains of sound
      pulses delivered at different pulse repetition rates (PRRs) under free-field
      stimulation conditions. All 66 neurons isolated from eight bats either discharged
      one to two impulses (phasic on responders, n = 41, 62%), three to eight impulses
      (phasic bursters, n = 19, 29%), or many impulses throughout the entire duration
      of the stimulus (tonic responders, n = 6, 9%). Whereas 50 neurons responded
      vigorously to frequency-modulated (FM) pulses, 16 responded poorly or not at all
      to FM pulses. Bicuculline application increased the number of impulses of all 66
      neurons in response to 4 ms pulses by 15-1,425%. The application also changed
      most phasic on responders into phasic bursters or tonic responders, resulting in
      12 (18%) phasic on responders, 34 (52%) phasic bursters, and 20 (30%) tonic
      responders. Response latencies of these neurons were either shortened (n = 25,
      38%) by 0.5-6.0 ms, lengthened (n = 9, 14%) by 0. 5-2.5 ms or not changed (n =
      32, 48%) on bicuculline application. Each neuron had a highest response
      repetition rate beyond which the neuron failed to respond. Bicuculline
      application increased the highest response repetition rates of 62 (94%) neurons
      studied. The application also increased the highest 100% pulse-locking repetition
      rates of 21 (32%) neurons and facilitated 27 (41%) neurons in response to more
      pulses at the same PRR than predrug conditions. According to average rate-based
      modulation transfer functions (average rate MTFs), all 66 neurons had low-pass
      filtering characteristics both before and after bicuculline application.
      According to total discharge rate-based modulation transfer functions (total rate
      MTFs), filtering characteristics of these neurons can be described as band-pass
      (n = 52, 79%), low-pass (n = 12, 18%), or high-pass (n = 2, 3%) before
      bicuculline application. Bicuculline application changed the filtering
      characteristics of 14 (21%) neurons. According to synchronization coefficient
      based modulation transfer functions, filtering characteristics of these neurons
      can be described as low-pass (n = 41, 62%), all-pass (n = 11, 17%), band
      suppression (n = 7, 10.5%), and band-suppression-band-pass filters (n = 7,
      10.5%). Bicuculline application changed filtering characteristics of 19 (29%)
      neurons.

PMID- 9582207
TI  - Roles of ascending inhibition during two rhythmic motor patterns in Xenopus
      tadpoles.
AB  - We have investigated the effects of ascending inhibitory pathways on two
      centrally generated rhythmic motor patterns in a simple vertebrate model, the
      young Xenopus tadpole. Tadpoles swim when touched, but when grasped respond with
      slower, stronger struggling movements during which the longitudinal pattern of
      motor activity is reversed. Surgical spinal cord transection to remove all
      ascending connections originating caudal to the transection (in tadpoles
      immobilized in alpha-bungarotoxin) did not affect "fictive" swimming generated
      more rostrally. In contrast, cycle period and burst duration both significantly
      increased during fictive struggling. Increases were progressively larger with
      more rostral transection. Blocking caudal activity with the anesthetic MS222
      (pharmacological transection) produced equivalent but reversible effects.
      Reducing crossed-ascending inhibition selectively, either by midsagittal spinal
      cord division or rostral cord hemisection (1-sided transection) mimicked the
      effects of transection. Like transection, both operations increased cycle period
      and burst duration during struggling but did not affect swimming. The changes
      during struggling were larger with more rostral hemisection. Reducing crossed
      ascending inhibition by spinal hemisection also increased the rostrocaudal
      longitudinal delay during swimming, and the caudorostral delay during struggling.
      Weakening inhibition globally with low concentrations of the glycine antagonist
      strychnine (10-100 nM) did not alter swimming cycle period, burst duration, or
      longitudinal delay. However, strychnine at 10-60 nM decreased cycle period during
      struggling. It also increased burst duration in some cases, although burst
      duration increased as a proportion of cycle period in all cases. Strychnine
      reduced longitudinal delay during struggling, making rostral and caudal activity
      more synchronous. At 100 nM, struggling was totally disrupted. By combining our
      results with a detailed knowledge of tadpole spinal cord anatomy, we conclude
      that inhibition mediated by the crossed-ascending axons of characterized,
      glycinergic, commissural interneurons has a major influence on the struggling
      motor pattern compared with swimming. We suggest that this difference is a
      consequence of the larger, reversed longitudinal delay and the extended burst
      duration during struggling compared with swimming.

PMID- 9582208
TI  - Transient disturbances to one limb produce coordinated, bilateral responses
      during infant stepping.
AB  - Transient disturbances were applied to the lower limbs of infants (3-10 mo of
      age) while they were supported to stepped on a treadmill. The aim was to
      determine how stepping infants respond to novel disturbances that would disrupt
      equilibrium during independent walking. Their responses were also compared with
      those from lower mammals and adult humans. In the first series of experiments,
      the motion of the limb in the swing phase was transiently stopped by the
      experimenter grasping the limb for a short time (0.1-1.7 s). During such
      disturbances, the stance phase was prolonged in the contralateral limb, and the
      onset of the swing phase was delayed. The degree to which the stepping was
      modified in the contralateral limb depended on the amount of load experienced by
      that limb. If the contralateral limb was bearing very little weight at the time
      of the disturbance, its rhythm did not change appreciably. In the second series
      of experiments, load was added to the infant by pushing down on the pelvis during
      the stance phase. This greatly prolonged the stance phase and delayed the swing
      phase. It did not increase the amplitude of the extensor electromyogram (EMG) of
      the loaded limb. In conclusion, the neural circuitry controlling stepping in the
      infants responds to disturbances in an organized fashion that is conducive to
      maintaining equilibrium and forward progression.

PMID- 9582209
TI  - Voltage-gated and Ca2+-activated conductances mediating and controlling graded
      electrical activity in crayfish muscle.
AB  - Crayfish opener muscle fibers provide a unique preparation to quantitatively
      evaluate the relationships between the voltage-gated Ca2+ (ICa) and Ca2+
      activated K+ (IK(Ca)) currents underlying the graded action potentials (GAPs)
      that typify these fibers. ICa, IK(Ca), and the voltage-gated K+ current (IK) were
      studied using two-electrode voltage-clamp applying voltage commands that
      simulated the GAPs evoked in current-clamp conditions by 60-ms current pulses.
      This methodology, unlike traditional voltage-clamp step commands, provides a
      description of the dynamic aspects of the interaction between different
      conductances participating in the generation of the natural GAP. The initial
      depolarizing phase of the GAP was due to activation of the ICa on depolarization
      above approximately -40 mV. The resulting Ca2+ inflow induced the activation of
      the fast IK(Ca) (<3 ms), which rapidly repolarized the fiber (<6 ms). Because of
      its relatively slow activation, the contribution of IK to the GAP repolarization
      was delayed. During the final steady GAP depolarization ICa and IK(Ca) were
      simultaneously activated with similar magnitudes, whereas IK aided in the control
      of the delayed sustained response. The larger GAPs evoked by higher intensity
      stimulations were due to the increase in ICa. The resulting larger Ca2+ inflow
      increased IK(Ca), which acted as a negative feedback that precisely controlled
      the fiber's depolarization. Hence IK(Ca) regulated the Ca2+-inflow needed for the
      contraction and controlled the depolarization that this Ca2+ inflow would
      otherwise elicit.

PMID- 9582210
TI  - Activation kinetics of the delayed rectifier potassium current of bullfrog
      sympathetic neurons.
AB  - We examined the activation kinetics of the delayed rectifier K+ current of
      bullfrog sympathetic neurons, primarily using whole cell recording. On
      depolarization, currents activated with a sigmoid delay but did not show a Cole
      Moore shift. The time course of activation differed systematically from an
      exponential raised to a power. At most voltages, a power of 2 gave the best
      overall fit but a power of 3 better described the initial delay. After the delay,
      the time course could be fitted by a single exponential. Time constants were 15
      20 ms at 0 mV and decreased to a limiting tau = 7 ms at +50 to +100 mV. Tail
      currents were well fitted by single exponential functions and accelerated with
      hyperpolarization, from tau = 15-20 ms at 0 mV to tau = 2 ms at -110 mV (e-fold
      for 40 mV). Eleven kinetic models were evaluated for their ability to describe
      the activation kinetics of the delayed rectifier. Hodgkin-Huxley-like models did
      not fit the data well. A linear model where voltage sensor movement is followed
      by a distinct channel opening step, allosteric models based on the Monod-Wyman-
      Changeux model, and an unconstrained C-C-C-O model could describe whole cell data
      from -100 to +40 mV. After including whole cell data at +60 and +80 mV, and a
      maximal p(open) of 0.8 from noise analysis of cell-attached patches, an
      allosteric model fit the data best, as the other models had difficulty describing
      qualitative features of the data. However, some more complex schemes (with
      additional free parameters) cannot be excluded. We propose the allosteric model
      as an empirical description of macroscopic ionic currents, and as a model worth
      considering in future studies on the molecular mechanism of potassium channel
      gating.

PMID- 9582211
TI  - Regulation of action-potential firing in spiny neurons of the rat neostriatum in
      vivo.
AB  - Both silent and spontaneously firing spiny projection neurons have been described
      in the neostriatum, but the reason for their differences in firing activity are
      unknown. We compared properties of spontaneously firing and silent spiny neurons
      in urethan-anesthetized rats. Neurons were identified as spiny projection neurons
      after labeling by intracellular injection of biocytin. The threshold for action
      potential firing was measured under three different conditions: 1) electrical
      stimulation of the contralateral cerebral cortex, 2) brief directly applied
      current pulses, and 3) spontaneous action-potentials occurring during spontaneous
      episodes of depolarization ( state). The average membrane potential and the
      amplitude of noiselike fluctuations of membrane potential in the state were
      determined by fitting a Gaussian curve to the membrane-potential distribution.
      All neurons in the sample exhibited spontaneous membrane potential shifts between
      a hyperpolarized state and a depolarized state, but not all fired action
      potentials while in the state. The difference between the spontaneously firing
      and the silent spiny neurons was in the average membrane potential in the state,
      which was significantly more depolarized in the spontaneously firing than in the
      silent spiny neurons. There were no significant differences in the threshold, the
      amplitude of the noiselike fluctuations of membrane potential in the state, or in
      the proportion of time that the membrane potential was in the state. In both
      spontaneously firing and silent neurons, the threshold for action potentials
      evoked by current pulses was significantly higher than for those evoked by
      cortical stimulation. Application of more intense current pulses that reproduced
      the excitatory postsynaptic potential rate of rise produced firing at
      correspondingly lower thresholds. Because the membrane potential in the state is
      mainly determined by the balance between the synaptic drive and the outward
      potassium conductances activated in the subthreshold range of membrane
      potentials, either or both of these factors may determine whether firing occurs
      in response to spontaneous afferent activity.

PMID- 9582212
TI  - Pattern of cardiorespiratory afferent convergence to solitary tract neurons
      driven by pulmonary vagal C-fiber stimulation in the mouse.
AB  - The central integration of signals from pulmonary vagal C-fibers (or type-J
      receptors) with those arising from cardiac, peripheral chemoreceptor, and
      baroreceptor afferents to neurons within the nucleus of the solitary tract (NTS)
      was studied in an arterially perfused working heart-brain stem preparation of
      adult mouse. Pulmonary vagal C-fibers were excited by right atrial injection of
      phenylbiguanide (PBG) while cardiac receptors were stimulated by left ventricular
      injection of veratridine (1-3 micrograms/kg) or mechanically by distension of the
      left ventricle (20-50 microl perfusate) using an indwelling cannula. Carotid body
      chemoreceptors were activated by aortic injection of Na cyanide, whereas
      baroreceptors were stimulated by increasing arterial perfusion pressure.
      Stimulation of pulmonary C-fibers and cardiac, chemo-, and baroreceptors all
      produced a reflex bradycardia (23-133 bpm). Central respiratory activity, as
      recorded from the phrenic nerve, was depressed by stimulating pulmonary C-fibers
      and cardiac and baroreceptors but enhanced in amplitude and frequency during
      chemoreceptor stimulation. Twenty-seven NTS neurons were excited and three were
      inhibited after pulmonary C-fiber stimulation displaying decrementing discharges
      with a peak firing frequency of up to 42 Hz (15 +/- 2.2 Hz, mean +/- SE) that
      lasted for 8.8 +/- 0.9 s. These responses occurred <1 s from the end of the PBG
      injection that was within the pulmonary circulation time. None of these cells
      responded to increases in right atrial pressure. All cells excited by PBG were
      also driven synaptically after electrical stimulation of the ipsilateral cervical
      vagus nerve at a latency of 32.9 +/- 3.2 ms (range 20-62 ms). None of these
      neurons had ongoing activity related to central respiratory activity. Convergence
      from cardiorespiratory afferents to 21 neurons driven by pulmonary C-fibers was
      tested. Twenty-five percent of cells were selectively excited by chemical
      stimulation of cardiac receptors alone, 19% were driven by peripheral
      chemoreceptors, and 38% responded to both cardiac and chemoreceptor activation.
      In contrast, only 13% of the cells activated by PBG injection responded to
      stimulation of baroreceptors and only 6% to cardiac mechanoreceptor stimulation.
      None of these neurons were activated by increasing right atrial pressure. The
      data indicate a high proportion of afferent convergence from pulmonary C-fibers,
      cardiac receptors, and peripheral chemoreceptors in the NTS. However, these
      neurons appear not to integrate inputs from cardiovascular mechanoreceptors. The
      significance of the data is discussed in relation to pathological disease states
      such as pulmonary congestion and cardiac failure.

PMID- 9582213
TI  - Convergence properties of solitary tract neurons responsive to cardiac receptor
      stimulation in the anesthetized cat.
AB  - The convergence pattern of cardiac receptors, pulmonary C-fibers, carotid
      chemoreceptor, and baroreceptor afferents onto neurons within the nucleus of the
      solitary tract (NTS) was studied in the anesthetized (pentobarbitone sodium, 40
      mg/kg,) paralyzed and artificially ventilated cat. Extra- and intracellular
      recordings were made from NTS neurons while stimulating both cardiac receptors by
      aortic root injections of veratridine (1-3 micrograms/kg) and pulmonary C-fibers
      by a right atrial injection of phenylbiguanide (10-20 micrograms/kg). The
      ipsilateral carotid body was stimulated by using arterial injection of CO2
      saturated bicarbonate solution, whereas inflation of the ipsilateral carotid
      sinus was used to activate baroreceptors. The ipsilateral cardiac vagal branch,
      cervical vagus, and carotid sinus nerves were stimulated electrically (1 Hz, 0.2
      1 ms, 1-35 V). In 78 NTS neurons recorded either extracellularly (n = 47) or
      intracellularly (n = 31), electrical stimulation of the cardiac branch of the
      vagus nerve evoked synaptic potentials (spikes and/or excitatory postsynaptic
      potentials) with an onset latency between 4 and 220 ms. Some neurons displayed
      both short and long latency inputs(15.5 +/- 1.8 and 160.0 +/- 8.5 ms; n = 14). Of
      these 78 neurons, 24 responded to veratridine stimulation of cardiac receptors
      (i.e., cardioreceptive neurons) by exhibiting an augmenting-decrementing
      discharge of 37 +/- 4 s in duration with a peak frequency of 30 +/- 5 Hz.
      Convergence from other cardiorespiratory receptors was noted involving either
      carotid chemoreceptors (n = 7) or pulmonary C-fibers (n = 4) or from both carotid
      chemoreceptors and pulmonary C-fibers (n = 6). In contrast, only one
      cardioreceptive NTS neuron was activated by distension of the carotid sinus.
      Recording sites recovered were confined to the medial NTS at the level of the
      area postrema and extended caudally into the commissural subnucleus. Our results
      indicate a convergence of carotid chemoreceptor and pulmonary C-fiber afferent
      inputs to cardioreceptive NTS neurons. With the paucity of baroreceptor inputs to
      these neurons it is suggested that sensory integration within the NTS may reflect
      regulatory versus defensive or protective reflex control.

PMID- 9582215
TI  - Correlation analysis of corticotectal interactions in the cat visual system.
AB  - We have studied the temporal relationship between visual responses in various
      visual cortical areas [17, 18, postero medial lateral suprasylvian (PMLS),
      postero lateral lateral suprasylvian (PLLS), 21a]) and the superficial layers of
      the cat superior colliculus (SC). To this end, simultaneous recordings were
      performed in one or several visual cortical areas and the SC of anesthetized
      paralyzed cats, and visually evoked multiunit responses were subjected to
      correlation analysis. Significant correlations occurred in 117 (24%) of 489
      cortex-SC pairs and were found for all cortical areas recorded. About half of the
      significant correlograms showed an oscillatory modulation. In these cases,
      oscillation frequencies covered a broad range, the majority being in the alpha-
      and beta-band. On average, significant center peaks in cross-correlograms had a
      modulation amplitude of 0.34. Our analysis revealed a considerable intertrial
      variability of correlation patterns with respect to both correlation strength and
      oscillation frequency. Furthermore, cortical areas differed in their
      corticotectal correlation patterns. The percentage of cells involved a
      corticotectal correlation, as well as the percentage of significantly modulated
      correlograms in such cases, was low for areas 17 and PMLS but high for areas 18
      and PLLS. Analysis of the cortical layers involved in these interactions showed
      that consistent temporal relationships between cortical and collicular responses
      were not restricted to layer V. Our data demonstrate a close relationship between
      corticotectal interactions and intracortical or intracollicular synchronization.
      Trial-by-trial analysis from these sites revealed a clear covariance of
      corticotectal correlations with intracortical synchronization. The probability of
      observing corticotectal interactions increased with enhanced local cortical and
      collicular synchronization and, in particular, with interareal cortical
      correlations. Corticotectal correlation patterns resemble in many ways those
      described among areas of the visual cortex. However, the correlations observed
      are weaker than those between nearby cortical sites, exhibit usually broader
      peaks and for some cortical areas show consistent phase-shifts. Corticotectal
      correlations represent population phenomena that reflect both the local and
      global temporal organization of activity in the cortical and collicular network
      and do not arise from purely monosynaptic interactions. Our findings show that
      both striate and extrastriate inputs affect the superficial SC in a cooperative
      manner and, thus, do not support the view that responses in the superficial SC
      depend exclusively on input from the primary visual areas as implied by the
      concept of "two corticotectal systems." We conclude that the corticotectal
      projections convey temporal activation patterns with high reliability, thus
      allowing the SC evaluation of information encoded in the temporal relations
      between responses of spatially disseminated cortical neurons. As a consequence,
      information distributed across multiple cortical areas can affect the SC neurons
      in a coherent way.

PMID- 9582214
TI  - Thalamic locus mediates hypoxic inhibition of breathing in fetal sheep.
AB  - The effects of lesions rostral to the brain stem on breathing responses to
      hypoxia were determined in chronically catheterized fetal sheep (>0.8 term).
      These studies were designed to test the hypothesis that the diencephalon is
      involved in hypoxic inhibition of fetal breathing. As in normal fetuses, hypoxia
      inhibited breathing with transection rostral to the thalamus or transection
      resulting in virtual destruction of the thalamus but sparing most of the
      parafascicular nuclear complex. Neuronal lesions were produced in the fetal
      diencephalon by injecting ibotenic acid through cannulas implanted in the brain.
      Hypoxic inhibition of breathing was abolished when the lesions encompassed the
      parafascicular nuclear complex but was retained when the lesions spared the
      parafascicular nuclear region or when the vehicle alone was injected. A new locus
      has been identified immediately rostral to the midbrain, which is crucial to
      hypoxic inhibition of fetal breathing. This thalamic sector involves the
      parafascicular nuclear complex and may link central O2-sensing cells to
      motoneurons that inhibit breathing.

PMID- 9582216
TI  - Picrotoxin eliminates frequency selectivity of an auditory interneuron in a
      bushcricket.
AB  - AN1, an auditory interneuron in the bushcricket Ancistrura nigrovittata, is
      narrowly tuned to the male song frequency ( approximately 15 kHz). It receives
      pronounced inhibitory input at frequencies below and, more prominently, above
      this fundamental frequency. It is also subject to side-dependent inhibition
      producing asymmetric response functions for left- and right-side stimulation. In
      addition, intensity-response functions of AN1 peak as stimulus intensities
      increase. Application of the GABAA channel-blocker picrotoxin eliminates all
      subthreshold inhibitory postsynaptic potentials, revealing underlying excitation
      that is particularly obvious in the high-frequency range. Excitatory thresholds
      close to the song frequency remain unchanged by picrotoxin. Thus a specifically
      tuned neuron is shown to become broadly tuned after elimination of frequency
      dependent inhibition. Although average maximum response strength is increased by
      150% after picrotoxin application, at male song frequencies a slight reduction of
      the responses is still present at high intensities. Side-dependent inhibition
      remains largely unaffected by picrotoxin, suggesting that side- and frequency
      dependent inhibitions are caused by different transmitters from different
      neurons.

PMID- 9582217
TI  - IID sensitivity differs between two principal centers in the interaural intensity
      difference pathway: the LSO and the IC.
AB  - Interaural intensity differences (IIDs) are the chief cues that animals use to
      localize high-frequency sounds. Neurons that are sensitive to IIDs are excited by
      sound at one ear and inhibited by sound at the other. Thus a given IID generates
      a combination of excitation and inhibition that is reflected in a cell's spike
      count. In mammals, the so-called "IID pathway" begins in the lateral superior
      olive (LSO), which is dominated by the type of IID-sensitive neurons just
      described. The LSO then sends a prominent projection to the inferior colliculus
      (IC), which also contains a substantial population of IID-sensitive cells. Recent
      pharmacological studies have suggested that the response properties of IID
      sensitive neurons in the IC undergo considerable processing and thus should not
      simply reflect the output of the LSO. However, we have no direct evidence as to
      whether IID sensitivity, the defining response feature of these cells, differs at
      these two levels. The present study makes this direct comparison in the Mexican
      free-tailed bat, a species that relies greatly on high-frequency hearing and thus
      on IIDs for localizing sounds in space. Extracellular recording techniques were
      used to obtain IID functions from 50 IC neurons. Comparable data from 50 LSO
      cells were available from a previous study. The main result was that IID
      sensitivity significantly differed between cells in the LSO and the IC. Among LSO
      cells, sensitivity was centered approximately 0 dB (no intensity difference
      between the ears) whereas, in the IC, sensitivity was biased toward the
      inhibitory ear: on average, IC cells required a more intense signal at the
      inhibitory ear to reach the same degree of suppression as observed in LSO cells.
      Further analysis showed that the vast majority of IC cells (88%) exhibited a
      mismatch in the latencies of their inputs: inhibition arrived later when an
      equally strong excitation and inhibition were elicited; this reduced the
      effectiveness of the inhibition. Because latency shortens with increasing
      stimulus intensity, an IID with a more intense signal at the inhibitory ear could
      equate the latencies of excitation and inhibition, increasing the effectiveness
      of the inhibition. This result suggests that latency mismatches account, to a
      great extent, for the difference in sensitivity between the LSO and the IC; and
      when mismatches were negated by electronically time shifting the signals to the
      ears, sensitivity was no longer significantly different between the two nuclei.

PMID- 9582218
TI  - Synaptically evoked dendritic action potentials in rat neocortical pyramidal
      neurons.
AB  - In a previous study iontophoresis of glutamate on the apical dendrite of layer 5
      pyramidal neurons from rat neocortex was used to identify sites at which
      dendritic depolarization evoked small, prolonged Ca2+ spikes and/or low-threshold
      Na+ spikes recorded by an intracellular microelectrode in the soma. These spikes
      were identified as originating in the dendrite. Here we evoke similar dendritic
      responses by electrical stimulation of presynaptic elements near the tip of the
      iontophoretic electrode with the use of a second extracellular electrode. In 9 of
      12 recorded cells, electrically evoked excitatory postsynaptic potentials (EPSPs)
      above a minimum size triggered all-or-none postsynaptic responses similar to
      those evoked by dendritic glutamate iontophoresis at the same site. Both the
      synaptically evoked and the iontophoretically evoked depolarizations were
      abolished reversibly by blockade of glutamate receptors. In all recorded cells,
      the combination of iontophoresis and an EPSP, each of which was subthreshold for
      the dendritic spike when given alone, evoked a dendritic spike similar to that
      evoked by a sufficiently large iontophoresis. In one cell tested, dendritic
      spikes could be evoked by the summation of two independent subthreshold EPSPs
      evoked by stimulation at two different locations. We conclude that the dendritic
      spikes are not unique to the use of glutamate iontophoresis because similar
      spikes can be evoked by EPSPs. We discuss the implications of these results for
      synaptic integration and for the interpretation of recorded synaptic potentials.

PMID- 9582219
TI  - Effects of cerebellar nuclear inactivation on the learning of a complex forelimb
      movement in cats.
AB  - The purpose of this study was to determine the effects of inactivating
      concurrently the cerebellar interposed and dentate nuclei on the capacity of cats
      to acquire and retain a complex, goal-directed forelimb movement. To assess the
      effects on acquisition, cats were required to learn to move a vertical
      manipulandum bar through a two-segment template with a shape approximating an
      inverted "L" after the injection of muscimol (saline for the control group) in
      the interposed and dentate cerebellar nuclei. During training periods, they were
      exposed progressively to more difficult templates, which were created by
      decreasing the angle between the two segments of the template. After determining
      the most difficult template the injected animals could learn within the specified
      time and performance constraints, the retraining phase of the experiment was
      initiated in which the cats were required to execute the same sequence of
      templates in the absence of any injection. This stage of the experiment assessed
      retention and determined the extent of any relearning required to execute the
      task at criterion levels. Next, the animals were overtrained without any
      injection on the most difficult template they could perform. Finally, to
      determine the effects of nuclear inactivation on retention after extensive
      retraining, their capacity to perform the same template was determined after
      muscimol injection in the interposed and dentate nuclei. The findings show that
      during the inactivation of the dentate and interposed nuclei the animals could
      learn to execute the more difficult templates. However, when required to execute
      the most difficult template learned under muscimol on the day after injections
      were discontinued, the cats had to "relearn" (reacquire) the movement. Finally,
      when the cerebellar nuclei were inactivated after the animals learned the task in
      the absence of any injections during the retraining phase, retention was not
      blocked. The data indicate that the intermediate and lateral cerebellum are not
      required either for learning this type of complex voluntary movement or for
      retaining the capacity to perform the task once it is learned. Nevertheless, when
      the cerebellum becomes available for executing a task learned in the absence of
      this structure, reacquisition of the behavior usually is necessary. It is
      hypothesized that the relearning observed after acquisition during muscimol
      inactivation reflects the tendency of the system to incorporate the cerebellum
      into the interactions responsible for the learning and performance of a motor
      sequence that is optimal for executing the task.

PMID- 9582220
TI  - Neural modulation of gut motility by myomodulin peptides and acetylcholine in the
      snail Lymnaea.
AB  - Families of peptide neuromodulators are believed to play important roles in
      neural networks that control behaviors. Here, we investigate the expression and
      role of one such group of modulators, the myomodulins, in the feeding system of
      Lymnaea stagnalis. Using a combination of in situ hybridization and antibody
      staining, expression of the myomodulin gene was confirmed in a number of
      identified behaviorally significant neuronal types, including the paired B2 motor
      neurons. The B2 cells were shown to project axons to the proesophagus, where they
      modulate foregut contractile activity. The presence of the five myomodulin
      peptide structures was confirmed in the B2 cells, the proesophagus, and the
      intervening nerve by mass spectrometry. Using a sensitive cell culture assay,
      evidence that the B2 cells are cholinergic also is presented. Application of four
      of the five myomodulin peptides to the isolated foregut increased both
      contraction frequency and tonus, whereas the main effect of acetylcholine (ACh)
      application was a large tonal contraction. The fifth myomodulin peptide
      (pQIPMLRLamide) appeared to have little or no effect on gut motility.
      Coapplication of all five myomodulin peptides gave a greater increase in tonus
      than that produced by the peptides applied individually, suggesting that
      corelease of the peptides onto the gut would produce an enhanced response. The
      combined effects that the myomodulin peptides and ACh have on foregut motility
      can mimic the main actions of B2 cell stimulation.

PMID- 9582221
TI  - Complex synaptic current waveforms evoked in hippocampal pyramidal neurons by
      extracellular stimulation of dentate gyrus.
AB  - Excitatory postsynaptic currents (EPSCs) evoked in hippocampal CA3 pyramidal
      neurons by extracellular stimulation of the dentate gyrus typically exhibit
      complex waveforms. They commonly have inflections or notches on the rising phase;
      the decay phase may exhibit notches or other obvious departures from a simple
      monoexponential decline; they often display considerable variability in the
      latency from stimulation to the peak current; and the rise times tend to be long.
      One hypothesis is that these complex EPSC waveforms might result from excitation
      via other CA3 pyramidal cells that were recruited antidromically or trans
      synaptically by the stimulus due to the complex anatomy of this region. An
      alternative hypothesis is that EPSC complexity does not emerge from the
      functional anatomy but rather reflects an unusual physiological property,
      intrinsic to excitation-secretion coupling in mossy-fiber (mf) synaptic
      terminals, that causes asynchronous quantal release. We evaluated certain
      predictions of our anatomic hypothesis by adding a pharmacological agent to the
      normal bathing medium that should suppress di- or polysynaptic responses. For
      this purpose we used baclofen (3 microM), a selective agonist for the gamma
      aminobutyric acid B receptor. The idea was that baclophen should discriminate
      against polysynaptic versus monosynaptic inputs by hyperpolarizing the cells,
      bringing them further from spike threshold and possibly also through inhibitory
      presynaptic actions. Whole cell recordings were done from visually preselected
      CA3 pyramidal neurons and EPSCs were evoked by fine bipolar electrodes positioned
      into the granule cell layer of the dentate. To the extent that the EPSC
      complexity reflects di- or polysynaptic responses, we predicted baclofen to
      reduce the number of notches on the rising and decay phases, reduce the variance
      in latency to peak of the EPSCs, decrease the amplitudes and rise times of the
      individual and averaged EPSCs, and increase the apparent failures in evoked
      EPSCs. All of these predictions were confirmed, in support of the hypothesis that
      these complex EPSC waveforms commonly reflect di- or polysynaptic responses. We
      also documented a distinctly different, intermittent, form of EPSC complexity,
      which also is predicted and easily explained by our anatomic hypothesis. In
      particular, the results were in accord with the suggestion that stimulation of
      the dentate gyrus might antidromically stimulate axon collaterals of CA3 neurons
      that make recurrent synapses onto the recorded cell. We conclude that the overall
      pattern of results is consistent with expectations based on the functional
      anatomy. The explanation does not demand a special type of intrinsic asynchronous
      mechanism for excitation-secretion coupling in the mf synapses.

PMID- 9582222
TI  - Passive electrical properties of ventral horn neurons in rat spinal cord slices.
AB  - Recordings were made from large neurons located in the ventral horn of transverse
      spinal cord slices from young rats (7-15 days). Whole cell recordings were made
      simultaneously with two electrodes from the soma of these neurons, visualized
      using infra-red differential interference contrast optics. Positive
      identification of motoneurons could not always be achieved. The response of a
      neuron to a brief pulse of current delivered by one electrode, and recorded by
      the other electrode, were matched optimally to responses of a compartmental model
      of the same neuron with an identical current pulse as input. The compartmental
      model was based on a reconstruction of the neuron, using Biocytin staining. The
      compartmental model had three free parameters: specific membrane capacitance
      (Cm), membrane resistivity (Rm), and cytoplasmatic resistivity (Ri), all assumed
      to be uniform throughout the neuron. The experimental and model responses could
      be matched unequivocally for four neurons, giving Cm = 2.4 +/- 0.5 microF/cm2, Rm
      = 5.3 +/- 0. 9 kOmega/cm2, and Ri = 87 +/- 22 Omega/cm. No somatic shunt was
      required. For the remaining six neurons, a less perfect fit (but still within 95%
      confidence limits) was indicative of nonhomogeneous membrane properties. The
      electrotonic length of uncut dendrites was 0.85 +/- 0.14 lambda. The results
      resolve the issue of a somatic shunt conductance for motoneurons, relegating it
      to a microelectrode impalement artifact. They are consistent with previous
      reports on the electrical compactness of motoneurons to steady state currents and
      voltages. However, the much higher value of Cm (than the previously assumed 1
      microF/cm2) implies much greater dendritic attenuation of fast synaptic
      potentials, and a much enhanced integrative response of motoneurons to synaptic
      potentials.

PMID- 9582223
TI  - Effects of quinine on the excitability and voltage-dependent currents of isolated
      spiral ganglion neurons in culture.
AB  - This work examined how quinine, a drug that induces both hearing loss and
      tinnitus, interfered with the excitability of spiral ganglion (SG) neurons in
      cultures. The membrane potential changes and the modification of the action
      potential waveform induced by quinine were studied in SG neurons under current
      clamp. The effects of the drug on voltage-dependent currents in SG neurons were
      also investigated by the voltage-clamp method. Quinine did not appreciably affect
      either resting membrane potentials or input resistance at rest. However, action
      potentials fired by SG neurons were significantly broadened by the presence of
      quinine. With higher concentrations of quinine (>20 microM), the amplitude of
      action potentials was also reduced. Voltage-clamp results demonstrated that
      quinine primarily blocked the whole cell potassium currents (IK) in a voltage
      dependent manner. Up to 100 microM of quinine did not appreciably block IK evoked
      by a test pulse to -35 mV. In contrast, IK was significantly reduced with more
      positive test pulses, e.g., the concentration needed to obtain 50% inhibition
      (IC50) was 8 microM for a test pulse to 65 mV. At higher concentrations (>20
      microM), quinine also reduced the size of sodium currents (INa) in a use
      dependent manner, while leaving calcium currents (ICa) relatively unaffected.
      Compared with the potency of quinine's effects on other targets in the inner ear,
      the relatively low IC50 and the voltage-dependent nature of quinine inhibition on
      IK suggested that its modulation of the waveform and threshold of action
      potentials of SG neurons probably was primarily responsible for its ototoxic
      effects. From the point of view of how neural signaling process is affected by
      the drug, quinine-induced tinnitus may be explained by its broadening of action
      potentials while the drug's inhibition on INa may result in hearing loss by
      making the conversion from excitatory postsynaptic potentials to the generation
      of action potentials more difficult.

PMID- 9582224
TI  - Diverse signal transduction pathways mediated by endogenous P2 receptors in
      cultured rat cerebral cortical neurons.
AB  - The present study was conducted to assess the intracellular signaling pathways
      mediated by receptors for ATP, uridine triphosphate (UTP), and 2-methylthio ATP
      (2-MeSATP), by monitoring patch-clamp currents and intracellular calcium
      mobilization in cultured rat cortical cerebral neurons. All three agonists evoked
      potassium currents and increased the intracellular free Ca2+ concentration
      ([Ca2+]i), and these effects were inhibited by the broad G-protein inhibitor
      guanosine-5'-O-(2-thiodiphosphate) (GDPbetaS) but not by the Gi/o-protein
      inhibitor pertussis toxin (PTX). UTP-evoked currents were inhibited by either the
      phospholipase C inhibitor neomycin or the selective protein kinase C (PKC)
      inhibitor GF109203X, and the rise in cytosolic Ca2+ was inhibited by either
      neomycin or the inositol 1,4,5-trisphosphate (IP3) receptor antagonist heparin,
      indicating that the UTP receptor involved phospholipase C-mediated
      phosphatidylinositol signaling. In contrast, 2-MeSATP-induced currents and rise
      in cytosolic Ca2+ were not inhibited by either neomycin, or GF109203X, or
      heparin. 2-MeSATP elicited single-channel currents in the cell-attached patch
      clamp configuration and also in excised patches. The G-protein activator GTP
      gamma S induced single-channel currents in a fashion that mimicked the effect of
      2-MeSATP. These data suggest that 2 MeSATP activated potassium channels by a
      direct action of G-protein beta gamma subunits and increased [Ca2+]i by a
      mechanism independent of phospholipase C stimulation and IP3 production. ATP
      evoked currents were partially inhibited by either neomycin or GF109203X,
      although the rise in cytosolic Ca2+ was not affected by these inhibitors. ATP
      produced single-channel currents with two major classes of the slope conductance
      (86 and 95 pS) in cell-attached patches, each of which is consistent with that
      achieved by 2-MeSATP (85 pS) or UTP (96 pS); the currents with the lower
      conductance were observed in the outside-out patch-clamp configuration. These
      results indicate that P2 receptors for UTP and 2-MeSATP are linked to a PTX
      insensitive G-protein involving different signal transduction pathways and that
      ATP responses are mediated by both of these P2 receptors.

PMID- 9582225
TI  - Specificity in the interaction of HVA Ca2+ channel types with Ca2+-dependent AHPs
      and firing behavior in neocortical pyramidal neurons.
AB  - Intracellular recordings and organic and inorganic Ca2+ channel blockers were
      used in a neocortical brain slice preparation to test whether high-voltage
      activated (HVA) Ca2+ channels are differentially coupled to Ca2+-dependent
      afterhyperpolarizations (AHPs) in sensorimotor neocortical pyramidal neurons. For
      the most part, spike repolarization was not Ca2+ dependent in these cells,
      although the final phase of repolarization (after the fast AHP) was sensitive to
      block of N-type current. Between 30 and 60% of the medium afterhyperpolarization
      (mAHP) and between approximately 80 and 90% of the slow AHP (sAHP) were Ca2+
      dependent. Based on the effects of specific organic Ca2+ channel blockers
      (dihydropyridines, omega-conotoxin GVIA, omega-agatoxin IVA, and omega-conotoxin
      MVIIC), the sAHP is coupled to N-, P-, and Q-type currents. P-type currents were
      coupled to the mAHP. L-type current was not involved in the generation of either
      AHP but (with other HVA currents) contributes to the inward currents that
      regulate interspike intervals during repetitive firing. These data suggest
      different functional consequences for modulation of Ca2+ current subtypes.

PMID- 9582226
TI  - Responses of neurons in the insular cortex to gustatory, visceral, and
      nociceptive stimuli in rats.
AB  - Extracellular unit responses to baroreceptor and chemoreceptor stimulation,
      gustatory stimulation of the posterior tongue, electrical stimulation of the
      superior laryngeal (SL) nerve, and tail pinch were recorded from the insular
      cortex of anesthetized and paralyzed rats. Forty-three neurons identified
      responded to stimulation by at least one of the stimuli used in the present
      study. Of the 43 neurons, 33 responded to tail pinch, and the remaining 10 had no
      response; 18 showed an excitatory response, and 15 showed an inhibitory response.
      Of the 43 neurons, 35 responded to electrical stimulation of the SL nerve; 27
      showed an excitatory response, and 8 showed an inhibitory response. Of the 20
      neurons that responded to baroreceptor stimulation by an intravenous injection of
      methoxamine hydrochloride (Mex), 11 were excitatory and 9 were inhibitory. Twenty
      seven neurons were responsive to an intravenous injection of sodium nitroprusside
      (SNP); 10 were excitatory and 17 were inhibitory. Ten neurons were excited and 16
      neurons were inhibited by arterial chemoreceptor stimulation by an intravenous
      injection of sodium cyanide (NaCN). Twenty-six neurons were responsive to at
      least one of the gustatory stimuli (1.0 M NaCl, 30 mM HCl, 30 mM quinine HCl, and
      1.0 M sucrose): four to six excitatory neurons and three to nine inhibitory
      neurons for each stimulus. A large number of the neurons (42/43) received
      convergent inputs from more than one stimulus among the nine stimuli used in the
      present study. Most neurons (38/43) were responsive to two or more stimulus
      groups when the natural stimuli used in the present study are grouped into three,
      gustatory, visceral, and nociceptive stimuli. The neurons recorded were located
      in the insular cortex between 2.8 mm anterior and 1.1 mm posterior to the
      anterior edge of the joining of the anterior commissure (AC); the mean location
      was 1.0 mm (n = 43) anterior to the AC. This indicates that most of the neurons
      identified in the present study were located in the region posterior to the taste
      area and anterior to the visceral area in the insular cortex. These results
      indicate that the insular cortex neurons distributing between the taste area and
      the visceral area receive convergent inputs from baroreceptor, chemoreceptor,
      gustatory, and nociceptive organs and may have roles in taste aversion or in
      regulation of visceral responses.

PMID- 9582228
TI  - Facilitation of a nociceptive flexion reflex in man by nonnoxious radiant heat
      produced by a laser.
AB  - Electromyographic recordings were made in healthy volunteers from the knee-flexor
      biceps femoris muscle of the nociceptive RIII reflex elicited by electrical
      stimulation of the cutaneous sural nerve. The stimulus intensity was adjusted to
      produce a moderate pricking-pain sensation. The test responses were conditioned
      by a nonnoxious thermal (</=40 degrees C) stimulus applied to the receptive field
      of the sural nerve. This stimulus was delivered by a CO2 laser stimulator and
      consisted of a 100-ms pulse of heat with a beam diameter of 20 mm. Its power was
      22.7 +/- 4.2 W (7.2 mJ/mm2), and it produced a sensation of warmth. The maximum
      surface temperature reached at the end of the period of stimulation was
      calculated to be 7 degrees C above the actual reference temperature of the skin
      (32 degrees C). The interval between the laser (conditioning) and electrical
      (test) stimuli was varied from 50 to 3, 000 ms in steps of 50 ms. It was found
      that the nociceptive flexion reflex was facilitated by the thermal stimulus; this
      modulation occurred with particular conditioning-test intervals, which peaked at
      500 and 1,100 ms with an additional late, long-lasting phase between 1,600 and
      2,300 ms. It was calculated that the conduction velocities of the cutaneous
      afferent fibers responsible for facilitating the RIII reflex, fell into three
      ranges: one corresponding to A delta fibers (3.2 m/s) and two in the C fiber
      range (1.3 and 0.7 m/s). It is concluded that information emanating from warm
      receptors and nociceptors converges. In this respect, the present data show, for
      the first time, that in man, conditioning nonnociceptive warm thermoreceptive A
      delta and C fibers results in an interaction at the spinal level with a
      nociceptive reflex. This interaction may constitute a useful means whereby
      signals add together to trigger flexion reflexes in defensive reactions and other
      basic motor behaviors. It also may contribute to hyperalgesia in inflammatory
      processes. The methodology used in this study appears to be a useful noninvasive
      tool for exploring the thermoalgesic mechanisms in both experimental and clinical
      situations.

PMID- 9582227
TI  - Neurotransmitter-induced novel modulation of a nonselective cation channel by a
      cAMP-dependent mechanism in rat pineal cells.
AB  - In the rat, circadian rhythm in melatonin is regulated by noradrenergic and
      neuropeptide inputs to the pineal via adenosine 3',5'-cyclic monophosphate (cAMP)
      and Ca2+-dependent mechanisms. We have identified a large conductance (170 pS),
      voltage-dependent, nonselective cation channel on rat pineal cells in culture
      that shows a novel mode of modulation by cAMP. Pituitary adenylate cyclase
      activating peptide (PACAP), norepinephrine, or 8-Br-cAMP increase channel open
      probability (Po) with a hyperpolarizing shift in voltage dependence such that the
      channel becomes active at resting membrane potentials. The increase in Po was
      accompanied by a change in current rectification properties such that the channel
      was transformed from being inactive at rest to an inwardly rectifying cation
      conductance in the presence of agonist, which depolarizes the cell. This channel
      is calcium insensitive, is blocked by Cs+, and shows a permeability sequence: K+
      > Na+ >/= NH+4 > Li+. The data suggest that PACAP and norepinephrine acting
      through a cAMP-dependent mechanism modulate this nonselective cation channel,
      resulting in a slow onset depolarization that may be important in regulation of
      pineal cell excitability.

PMID- 9582229
TI  - Dopamine receptor-mediated mechanisms involved in the expression of learned
      activity of primate striatal neurons.
AB  - To understand the mechanisms by which basal ganglia neurons express acquired
      activities during and after behavioral learning, selective dopamine (DA) receptor
      antagonists were applied while recording the activity of striatal neurons in
      monkeys performing behavioral tasks. In experiment 1, a monkey was trained to
      associate a click sound with a drop of reward water. DA receptor antagonists were
      administered by micropressure using a stainless steel injection cannula (300
      microm ID) through which a Teflon-coated tungsten wire for recording neuronal
      activity had been threaded. Responses to sound by tonically active neurons
      (TANs), a class of neurons in the primate striatum, were recorded through a
      tungsten wire electrode during the application of either D1- or D2-class DA
      receptor antagonists (total volume <1 microl, at a rate of 1 microl/5-10 min).
      Application of the D2-class antagonist, (-)-sulpiride (20 micrograms/microl, 58
      mM, pH 6.8), abolished the responses of four of five TANs examined. In another
      five TANs, neither the D2-class antagonist nor the D1-class antagonists, SCH23390
      (10 micrograms/microl, 31 mM, pH 5.7) or cis-flupenthixol (30 micrograms/microl,
      59 mM, pH 6.6) significantly suppressed responses. In experiment 2, four- or five
      barreled glass microelectrodes were inserted into the striatum. The central
      barrel was used for extracellular recording of activity of TANs. Each DA receptor
      antagonist was iontophoretically applied through one of the surrounding barrels.
      SCH23390 (10 mM, pH 4.5) and (-)-sulpiride (10 mM, pH 4.5) were used. The effects
      of iontophoresis of both D1- and D2-class antagonists were examined in 40 TANs.
      Of 40 TANs from which recordings were made, responses were suppressed exclusively
      by the D2-class antagonist in 19 TANs, exclusively by the D1-class antagonist in
      3 TANs, and by both D1- and D2-class antagonists in 7 TANs. When 0.9% NaCl,
      saline, was applied by pressure (<1 microl) or by iontophoresis (<30 nA) as a
      control, neither the background discharge rates nor the responses of TANs were
      significantly influenced. Background discharge rate of TANs was also not affected
      by D1- or D2-class antagonists applied by either micropressure injection or
      iontophoresis. It was concluded that the nigrostriatal DA system enables TANs to
      express learned activity primarily through D2-class and partly through D1-class
      receptor-mediated mechanisms in the striatum.

PMID- 9582230
TI  - GABA-receptor-independent dorsal root afferents depolarization in the neonatal
      rat spinal cord.
AB  - Dorsal root afferent depolarization and antidromic firing were studied in
      isolated spinal cords of neonatal rats. Spontaneous firing accompanied by
      occasional bursts could be recorded from most dorsal roots in the majority of the
      cords. The afferent bursts were enhanced after elevation of the extracellular
      potassium concentration ([K+]e) by 1-2 mM. More substantial afferent bursts were
      produced when the cords were isolated with intact brain stems. Rhythmic afferent
      bursts could be recorded from dorsal roots in some of the cords during motor
      rhythm induced by bath-applied serotonin and N-methyl--aspartate (NMDA).
      Bilaterally synchronous afferent bursts were produced in pairs of dorsal roots
      after replacing the NaCl in the perfusate with sodium-2-hydroxyethansulfonate or
      after application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist
      bicuculline with or without serotonin (5-HT) and NMDA. Antidromic afferent bursts
      also could be elicited under these conditions by stimulation of adjacent dorsal
      roots, ventrolateral funiculus axons, or ventral white commissural (VWC) fibers.
      The antidromic bursts were superimposed on prolonged dorsal root potentials
      (DRPs) and accompanied by a prolonged increase in intraspinal afferent
      excitability. Surgical manipulations of the cord revealed that afferent firing in
      the presence of bicuculline persisted in the hemicords after hemisection and
      still was observed after removal of their ventral horns. Cutting the VWC
      throughout its length did not perturb the bilateral synchronicity of the
      discharge. These findings suggest that the activity of dorsal horn neurons is
      sufficient to produce the discharge and that the bilateral synchronicity can be
      maintained by cross connectivity that is relayed from side to side dorsal to the
      VWC. Antagonists of GABAB, 5-HT2/5-HT1C, or glutamate metabotropic group II and
      III receptors could not abolish afferent depolarization in the presence of
      bicuculline. Depolarization comparable in amplitude to DRPs, could be produced in
      tetrodotoxin-treated cords by elevation of [K+]e to the levels reported to
      develop in the neonatal rat spinal cord in response to dorsal root stimulation. A
      mechanism involving potassium transients produced by neuronal activity therefore
      is suggested to be the major cause of the GABA-independent afferent
      depolarization reported in our study. Possible implications of potassium
      transients in the developing and the adult mammalian spinal cord are discussed.

PMID- 9582232
TI  - Caudal pontine reticular formation of C57BL/6J mice: responses to startle
      stimuli, inhibition by tones, and plasticity.
AB  - C57BL/6J (C57) mice were used to examine relationships between the behavioral
      acoustic startle response (ASR) and the responses of neurons in the caudal
      pontine reticular formation (PnC) in three contexts: 1) responses evoked by basic
      startle stimuli; 2) the prepulse inhibition (PPI) paradigm; and 3) the effects of
      high-frequency hearing loss and concomitant neural plasticity that occurs in
      middle-aged C57 mice. 1) Responses (evoked action potentials) of PnC neurons
      closely paralleled the ASR with respect to latency, threshold, and responses to
      rapidly presented stimuli. 2) "Neural PPI" (inhibition of responses evoked by a
      startle stimulus when preceded by a tone prepulse) was observed in all PnC
      neurons studied. 3) In PnC neurons of 6-mo-old mice with high-frequency (>20 kHz)
      hearing loss, neural PPI was enhanced with 12- and 4-kHz prepulses, as it is
      behaviorally. These are frequencies that have become "overrepresented" in the
      central auditory system of 6-mo-old C57 mice. Thus neural plasticity in the
      auditory system, induced by high-frequency hearing loss, is correlated with
      increased salience of the inhibiting tones in both behavioral and neural PPI
      paradigms.

PMID- 9582231
TI  - Differential effects of morphine on corneal-responsive neurons in rostral versus
      caudal regions of spinal trigeminal nucleus in the rat.
AB  - The initial processing of corneal sensory input in the rat occurs in two distinct
      regions of the spinal trigeminal nucleus, at the subnucleus interpolaris/caudalis
      transition (Vi/Vc) and in laminae I-II at the subnucleus caudalis/spinal cord
      transition (Vc/C1). Extracellular recording was used to compare the effects of
      morphine on the evoked activity of corneal-responsive neurons located in these
      two regions. Neurons also were characterized by cutaneous receptive field
      properties and parabrachial area (PBA) projection status. Electrical corneal
      stimulation-evoked activity of most (10/13) neurons at the Vi/Vc transition
      region was increased [146 +/- 16% (mean +/- SE) of control, P < 0.025] after
      systemic morphine and reduced after naloxone. None of the Vi/Vc corneal units
      were inhibited by morphine. By contrast, all corneal neurons recorded at the
      Vc/C1 transition region displayed a naloxone-reversible decrease (55 +/- 10% of
      control, P < 0.001) in evoked activity after morphine. None of 13 Vi/Vc corneal
      units and 7 of 8 Vc/C1 corneal units tested projected to the PBA. To determine if
      the Vc/C1 transition acted as a relay for the effect of intravenous morphine on
      corneal stimulation-evoked activity of Vi/Vc units, morphine was applied
      topically to the dorsal brain stem surface overlying the Vc/C1 transition. Local
      microinjection of morphine at the Vc/C1 transition increased the evoked activity
      of 4 Vi/Vc neurons, inhibited that of 2 neurons, and did not affect the remaining
      12 corneal neurons tested. In conclusion, the distinctive effects of morphine on
      Vi/Vc and Vc/C1 neurons support the hypothesis that these two neuronal groups
      contribute to different aspects of corneal sensory processing such as pain
      sensation, autonomic reflex responses, and recruitment of descending controls.

PMID- 9582233
TI  - Intrinsic and thalamic excitatory inputs onto songbird LMAN neurons differ in
      their pharmacological and temporal properties.
AB  - In passerine songbirds, the lateral portion of the magnocellular nucleus of the
      anterior neostriatum (LMAN) plays a vital role in song learning, possibly by
      encoding sensory information and providing sensory feedback to the vocal motor
      system. Consistent with this, LMAN neurons are auditory, and, as learning
      progresses, they evolve from a broadly tuned initial state to a state of strong
      preference for the bird's own song and acute sensitivity to the temporal order of
      this song. Moreover, normal synaptic activity in LMAN is required during sensory
      learning for accurate tutor song copying to occur (). To explore cellular and
      synaptic properties of LMAN that may contribute to this crucial stage of song
      acquisition, we developed an acute slice preparation of LMAN from zebra finches
      in the early stages of sensory learning (18-25 days posthatch). We used this
      preparation to examine intrinsic neuronal properties of LMAN neurons at this
      stage and to identify two independent excitatory inputs to these neurons and
      compare each input's pharmacology and short-term synaptic plasticity. LMAN
      neurons had immature passive membrane properties, well-developed spiking
      behavior, and received excitatory input from two sources: afferents from the
      medial portion of the dorsolateral thalamus (DLM), and recurrent axon collaterals
      from LMAN itself ("intrinsic" input). These two inputs differed in both their
      pharmacology and temporal properties. Both inputs were glutamatergic, but LMAN
      responses to intrinsic inputs exhibited a larger N-methyl--aspartate component
      than responses to DLM inputs. Both inputs elicited temporal summation in response
      to pairs of stimuli delivered at short intervals, but -2-amino-5
      phosphonovalerate (APV) significantly reduced the temporal summation only of the
      responses to intrinsic inputs. Moreover, responses to DLM inputs showed
      consistent paired-pulse depression, whereas the responses to intrinsic inputs did
      not. The differences between these two inputs suggest that intrinsic circuitry
      plays an important role in transforming DLM input patterns into the appropriate
      LMAN output patterns, as has been suggested for mammalian thalamocortical
      networks. Moreover, in LMAN, such interactions may contribute to the profound
      temporal and spectral selectivity that these neurons will acquire during
      learning.

PMID- 9582234
TI  - Processing of frequency-modulated sounds in the cat's posterior auditory field.
AB  - Single-neuron activity was recorded from the posterior auditory field (PAF) in
      the cortex of gas-anesthetized cats. Tone bursts and broadband complex sounds
      were used for auditory stimulation. Responses to frequency-modulated (FM) sounds,
      in particular, were studied systematically. Linear FM sweeps were centered around
      the best frequency (BF) of a neuron and had an excursion large enough to cover
      its whole frequency tuning range. Rate and direction of change of the FM sweeps
      were varied. In the majority of PAF neurons (75%) the FM response seemed not to
      be linear, i.e., their best instantaneous frequency (BIF) varied by more than one
      octave at different FM rates (FMR). When the difference between BIF and BF at
      each FMR was used as a measure of linearity, it was within one-third octave only
      at five or fewer FMR in most PAF neurons (74%). The majority of PAF neurons (70%)
      preferred moderate FM rates (<200 Hz/ms). Fifty-four percent of all neurons in
      this area showed band-pass behavior with a clear preference in the middle range
      of FM rates in at least one direction. Overall, neurons with high-pass behavior
      in both directions made up only a minor portion (22%) of PAF neurons. When both
      directions of an FM sweep (low-to-high and high-to-low frequency) were tested,
      50% of the neurons were clearly selective for one direction, i.e., the response
      to one FM direction was at least twice as large as that to the other direction.
      This selectivity was not necessarily present at the preferred FM rate. In
      general, FM direction selectivity was equally distributed over FM rates tested.
      The selectivity of PAF neurons for the rate and direction of FM sounds makes
      these neurons suitable for the detection and analysis of communication sounds,
      which often contain FM components with a moderate sweep rate in a particular
      direction.

PMID- 9582235
TI  - Extracellular K+ induces locomotor-like patterns in the rat spinal cord in vitro:
      comparison with NMDA or 5-HT induced activity.
AB  - Bath-application of increasing concentrations of extracellular K+ elicited
      alternating motor patterns recorded from pairs of various lumbar ventral roots of
      the neonatal rat (0-2 days old) spinal cord in vitro. The threshold concentration
      of K+ for this effect was 7.9 +/- 0.8 mM (mean +/- SD). The suprathreshold
      concentration range useful to evoke persistent motor patterns (lasting >/=10 min)
      was very narrow ( approximately 1 mM) as further increments elicited only
      rhythmic activity lasting from 20 s to a few minutes. On average, the fastest
      period of rhythmic patterns was 1.1 +/- 0.3 s. Intracellular recording from
      lumbar motoneurons showed that raised extracellular K+ elicited membrane
      potential oscillations with superimposed repetitive firing. In the presence of N
      methyl--aspartate (NMDA) or non-NMDA receptor blockers [R(-)-2-amino
      phosphonovaleric acid or 6-cyano-7-nitroquinoxaline-2,3-dione, respectively]
      extracellular K+ increases could still induce motor patterns although the
      threshold concentration was raised. Serotonin (5-HT) also induced alternating
      motor patterns (threshold 15 +/- 7 microM) that were consistently slower than
      those induced by high K+ or NMDA. Ritanserin (1 microM) prevented the locomotor
      like activity of 5-HT but not that of high K+ provided the concentration of the
      latter was further increased. Subthreshold concentrations of K+ became effective
      in the presence of subthreshold doses of 5-HT or NMDA, indicating mutual
      facilitation between these substances. The fastest pattern frequency was observed
      by raising K+ or by adding NMDA. In the presence of 5-HT, the pattern frequency
      was never as fast even if NMDA (or high K+) was coapplied. Furthermore,
      application of 5-HT significantly slowed down the K+- or NMDA-induced rhythm, an
      effect strongly potentiated in the presence of ritanserin. It is suggested that
      the operation of the spinal locomotor network was activated by rises in
      extracellular K+, which presumably led to a broad increase in neuronal
      excitability. Whenever the efficiency of excitatory synaptic transmission was
      diminished (for example by glutamate receptor antagonism), a larger concentration
      of K+ was required to evoke locomotor-like patterns. The complex effect
      (comprising stimulation and inhibition) of 5-HT on alternating pattern generation
      appeared to result from a dual action of this substance on the spinal locomotor
      network.

PMID- 9582236
TI  - Modeling control of eye orientation in three dimensions. I. Role of muscle
      pulleys in determining saccadic trajectory.
AB  - This study evaluates the effects of muscle axis shifts on the performance of a
      vector velocity-position integrator in the CNS. Earlier models of the oculomotor
      plant assumed that the muscle axes remained fixed relative to the head as the eye
      rotated into secondary and tertiary eye positions. Under this assumption, the
      vector integrator model generates torsional transients as the eye moves from
      secondary to tertiary positions of fixation. The torsional transient represents
      an eye movement response to a spatial mismatch between the torque axes that
      remain fixed in the head and the displacement plane that changes by half the
      angle of the change in eye orientation. When muscle axis shifts were incorporated
      into the model, the torque axes were closer to the displacement plane at each eye
      orientation throughout the trajectory, and torsional transients were reduced
      dramatically. Their size and dynamics were close to reported data. It was also
      shown that when the muscle torque axes were rotated by 50% of the eye rotation,
      there was no torsional transient and Listing's law was perfectly obeyed. When
      muscle torque axes rotated >50%, torsional transients reversed direction compared
      with what occurred for muscle axis shifts of <50%. The model indicates that
      Listing's law is implemented by the oculomotor plant subject to a two-dimensional
      command signal that is confined to the pitch-yaw plane, having zero torsion.
      Saccades that bring the eye to orientations outside Listing's plane could easily
      be corrected by a roll pulse that resets the roll state of the velocity-position
      integrator to zero. This would be a simple implementation of the corrective
      controller suggested by Van Opstal and colleagues. The model further indicates
      that muscle axis shifts together with the torque orientation relationship for
      tissue surrounding the eye and Newton's laws of motion form a sufficient plant
      model to explain saccadic trajectories and periods of fixation when driven by a
      vector command confined to the pitch-yaw plane. This implies that the velocity
      position integrator is probably realized as a subtractive feedback vector
      integrator and not as a quaternion-based integrator that implements kinematic
      transformations to orient the eye.

PMID- 9582237
TI  - Rescue of alpha-SNS sodium channel expression in small dorsal root ganglion
      neurons after axotomy by nerve growth factor in vivo.
AB  - Small (18-25 microm diam) dorsal root ganglion (DRG) neurons are known to express
      high levels of tetrodotoxin-resistant (TTX-R) sodium current and the mRNA for the
      alpha-SNS sodium channel, which encodes a TTX-R channel when expressed in
      oocytes. These neurons also preferentially express the high affinity receptor for
      nerve growth factor (NGF), TrkA. Levels of TTX-R sodium current and of alpha-SNS
      mRNA are reduced in these cells after axotomy. To determine whether NGF
      participates in the regulation of TTX-R current and alpha-SNS mRNA in small DRG
      neurons in vivo, we axotomized small lumbar DRG neurons by sciatic nerve
      transection and administered NGF or Ringer solution to the proximal nerve stump
      using osmotic pumps. Ten to 12 days after pump implant, whole cell patch-clamp
      recording demonstrated that TTX-R current density was decreased in Ringer-treated
      axotomized neurons (154 +/- 45 pA/pF; mean +/- SE) compared with nonaxotomized
      control neurons (865 +/- 123 pA/pF) and was restored partially toward control
      levels in NGF-treated axotomized neurons (465 +/- 78 pA/pF). The V1/2 for steady
      state activation and inactivation of TTX-R currents were similar in control,
      Ringer- and NGF-treated axotomized neurons. Reverse transcription polymerase
      chain reaction revealed an upregulation of alpha-SNS mRNA levels in NGF-treated
      compared with Ringer-treated axotomized DRG. In situ hybridization showed that
      alpha-SNS mRNA levels were decreased significantly in small Ringer-treated
      axotomized DRG neurons in vivo and also in small DRG neurons that were
      dissociated and maintained in vitro, so as to correspond to the patch-clamp
      conditions. NGF-treated axotomized neurons had a significant increase in alpha
      SNS mRNA expression, compared with Ringer-treated axotomized cells. These results
      show that the administration of exogenous NGF in vivo, to the proximal nerve
      stump of the transected sciatic nerve, results in an upregulation of TTX-R sodium
      current and of alpha-SNS mRNA levels in small DRG neurons. Retrogradely
      transported NGF thus appears to participate in the control of excitability in
      these cells via actions that include the regulation of sodium channel gene
      expression in vivo.

PMID- 9582238
TI  - Minimal model of oscillations and waves in the Limax olfactory lobe with tests of
      the model's predictive power.
AB  - Propagating waves are observed in the olfactory or procerebral (PC) lobe of the
      terrestrial mollusk, Limax maximus. Wave propagation is altered by cutting
      through the various layers of the PC lobe both parallel and transverse to the
      direction of wave propagation. We present a model for the PC lobe based on two
      layers of coupled cells. The top layer represents the cell layer of the PC lobe,
      and the bottom layer corresponds to the neuropil of the PC lobe. To get wave
      propagation, we induce a coupling gradient so that the most apical cells receive
      a greater input from neighbors than the basal cells. The top layer in the model
      is composed of oscillators coupled locally, whereas the bottom layer is comprised
      of oscillators with global coupling. Odor stimulation is represented by an
      increase in the strength of coupling between the two layers. This model allows us
      to explain a number of experimental observations: 1) the intact PC lobe exhibits
      regular propagating waves, which travel from the apical to the basal end; 2)
      there is a gradient in the local frequency of slices cut transverse to the axis
      of wave propagation, with apical slices oscillating faster than basal slices; 3)
      with partial cuts through the cell layer or the neuropil layer, the apical and
      basal ends remain tightly coupled; 4) removal of the neuropil layer does not
      prevent wave propagation in the cell layer; 5) odor stimulation causes the waves
      to collapse and the cells in the PC lobe oscillate synchronously; and 6) by
      allowing a single parameter to vary in the model, we capture the reversal of
      waves in low chloride medium.

PMID- 9582239
TI  - Control of spatial orientation of the angular vestibuloocular reflex by the
      nodulus and uvula.
AB  - Spatial orientation of the angular vestibuloocular reflex (aVOR) was studied in
      rhesus monkeys after complete and partial ablation of the nodulus and ventral
      uvula. Horizontal, vertical, and torsional components of slow phases of nystagmus
      were analyzed to determine the axes of eye rotation, the time constants (Tcs) of
      velocity storage, and its orientation vectors. The gravito-inertial acceleration
      vector (GIA) was tilted relative to the head during optokinetic afternystagmus
      (OKAN), centrifugation, and reorientation of the head during postrotatory
      nystagmus. When the GIA was tilted relative to the head in normal animals,
      horizontal Tcs decreased, vertical and/or roll time constants (Tc(vert/roll))
      lengthened according to the orientation of the GIA, and vertical and/or roll eye
      velocity components appeared (cross-coupling). This shifted the axis of eye
      rotation toward alignment with the tilted GIA. Horizontal and vertical/roll Tcs
      varied inversely, with T(chor) being longest and T(cvert/roll) shortest when
      monkeys were upright, and the reverse when stimuli were around the vertical or
      roll axes. Vertical or roll Tcs were longest when the axes of eye rotation were
      aligned with the spatial vertical, respectively. After complete nodulo
      uvulectomy, T(chor) became longer, and periodic alternating nystagmus (PAN)
      developed in darkness. T(chor) could not be shortened in any of paradigms tested.
      In addition, yaw-to-vertical/roll cross-coupling was lost, and the axes of eye
      rotation remained fixed during nystagmus, regardless of the tilt of the GIA with
      respect to the head. After central portions of the nodulus and uvula were
      ablated, leaving lateral portions of the nodulus intact, yaw-to-vertical/roll
      cross-coupling and control of Tc(vert/roll) was lost or greatly reduced. However,
      control of Tchor was maintained, and T(chor) continued to vary as a function of
      the tilted GIA. Despite this, the eye velocity vector remained aligned with the
      head during yaw axis stimulation after partial nodulo-uvulectomy, regardless of
      GIA orientation to the head. The data were related to a three-dimensional model
      of the aVOR, which simulated the experimental results. The model provides a basis
      for understanding how the nodulus and uvula control processing within the
      vestibular nuclei responsible for spatial orientation of the aVOR. We conclude
      that the three-dimensional dynamics of the velocity storage system are determined
      in the nodulus and ventral uvula. We propose that the horizontal and
      vertical/roll Tcs are separately controlled in the nodulus and uvula with the
      dynamic characteristics of vertical/roll components modulated in central portions
      and the horizontal components laterally, presumably in a semicircular canal-based
      coordinate frame.

PMID- 9582240
TI  - Cellular mechanisms underlying intrathalamic augmenting responses of reticular
      and relay neurons.
AB  - Augmenting (or incremental) responses are progressively growing potentials
      elicited by 5- to 15-Hz stimulation within the thalamus, cerebral cortex, or by
      setting into action reciprocal thalamocortical neuronal loops. These responses
      are associated with short-term plasticity processes in thalamic and cortical
      neurons. In the present study, in vivo intracellular recordings of thalamic
      reticular (RE) and thalamocortical (TC), as well as dual intracellular
      recordings, were used to explore the mechanisms of two types of intrathalamic
      augmenting responses elicited by thalamic stimuli at 10 Hz in decorticated cats.
      As recently described, after decortication, TC cells display incremental burst
      responses to thalamic stimuli that occur through either progressive
      depolarization (high threshold, HT) or progressive hyperpolarization leading to
      deinactivation of low-threshold (LT) spike bursts. Here, low-intensity stimuli
      (10 Hz) to dorsal thalamic nuclei elicited decremental responses in GABAergic RE
      cells, consisting of a progressive diminution in the number of action potentials
      in successive spike bursts, whereas higher stimulation (>50% of maximal strength)
      induced augmentation characterized by an increased number of spikes in repetitive
      responses. These opposing discharge patterns occurred in the absence of changes
      in the membrane potential of RE cells. In TC cells, augmentation depended on the
      thalamic site where testing volleys were applied. With stimuli applied closer to
      the site of impalement, augmenting resulted from a transformation from LT spike
      bursts into HT responses. Augmenting responses were followed by self-sustained
      oscillatory activity, within the frequency of spindles (7-14 Hz) or clock-like
      delta oscillation (1-4 Hz). As LT augmentation in TC cells results from their
      progressive hyperpolarization, we tested the effects exerted by the activating
      depolarizing system arising in the mesopontine cholinergic nuclei and found that
      such conditioning pulse-trains prevented the hyperpolarizing-rebound sequences as
      well as the LT augmenting in TC cells. We propose that the depolarization
      dependent (HT) augmenting responses in TC cells result from decremental responses
      in RE neurons that are due to intra-RE inhibitory processes leading to
      disinhibition in target TC neurons, whereas LT-type augmenting in TC cells is
      produced mainly by incremental responses in GABAergic RE neurons.

PMID- 9582241
TI  - Cellular and network models for intrathalamic augmenting responses during 10-Hz
      stimulation.
AB  - Repetitive stimulation of the thalamus at 7-14 Hz evokes responses of increasing
      amplitude in the thalamus and the areas of the neocortex to which the stimulated
      foci project. Possible mechanisms underlying the thalamic augmenting responses
      during repetitive stimulation were investigated with computer models of
      interacting thalamocortical (TC) and thalamic reticular (RE) cells. The ionic
      currents in these cells were modeled with Hodgkin-Huxley type of kinetics, and
      the results of the model were compared with in vivo thalamic recordings from
      decorticated cats. The simplest network model demonstrating an augmenting
      response was a single pair of coupled RE and TC cells, in which RE-induced
      inhibitory postsynaptic potentials (IPSPs) in the TC cell led to progressive
      deinactivation of a low-threshold Ca2+ current. The augmenting responses in two
      reciprocally interacting chains of RE and TC cells depended also on gamma
      aminobutyric acid-B (GABAB) IPSPs. Lateral GABAA inhibition between identical RE
      cells, which weakened bursts in these cells, diminished GABAB IPSPs and delayed
      the augmenting response in TC cells. The results of these simulations show that
      the interplay between existing mechanisms in the thalamus explains the basic
      properties of the intrathalamic augmenting responses.

PMID- 9582242
TI  - Human brain regions involved in direction discrimination.
AB  - To obtain further evidence for the functional specialization and task-dependent
      processing in the human visual system, we used positron emission tomography to
      compare regional cerebral blood flow in two direction discrimination tasks and
      four control tasks. The stimulus configuration, which was identical in all tasks,
      included the motion of a random dot pattern, dimming of a fixation point, and a
      tone burst. The discrimination tasks comprised the identification of motion
      direction and successive direction discrimination. The control tasks were motion
      detection, dimming detection, tone detection, and passive viewing. There was
      little difference in the activation patterns evoked by the three detection tasks
      except for decreased activity in the parietal cortex during the detection of a
      tone. Thus attention to a nonvisual stimulus modulated different visual cortical
      regions nonuniformly. Comparison of successive discrimination with motion
      detection yielded significant activation in the right fusiform gyrus, right
      lingual gyrus, right frontal operculum, left inferior frontal gyrus, and right
      thalamus. The fusiform and opercular activation sites persisted even after
      subtracting direction identification from successive discrimination, indicating
      their involvement in temporal comparison. Functional magnetic resonance imaging
      (fMRI) experiments confirmed the weak nature of the activation of human MT/V5 by
      successive direction discrimination but also indicated the involvement of an
      inferior satellite of human MT/V5. The fMRI experiments moreover confirmed the
      involvement of human V3A, lingual, and parietal regions in successive
      discrimination. Our results provide further evidence for the functional
      specialization of the human visual system because the cortical regions involved
      in direction discrimination partially differ from those involved in orientation
      discrimination. They also support the principle of task-dependent visual
      processing and indicate that the right fusiform gyrus participates in temporal
      comparison, irrespective of the stimulus attribute.

PMID- 9582243
TI  - Shift of visual fixation dependent on background illumination.
AB  - Visual fixation, the act of maintaining the eyes directed toward a location of
      interest, is a highly skilled behavior necessary for high-level vision in
      primates. In spite of its significance, visual fixation is not well understood;
      it is not even clear what attributes of the visual input are used to control
      fixation. Here we show, in four Macaca fascicularis monkeys, that the position
      the eyes assume during fixation depends on the luminance of the background. Dark
      background yields fixation positions that are shifted upward with respect to the
      fixation positions obtained with a dimly illuminated, featureless background.
      This phenomenon was observed previously in a nutshell by Snodderly; here first we
      rigorously establish its existence by testing proper controls. We then study the
      properties of this upshift of the fixation position. We show that, although the
      size of the upshift varies between monkeys, for all monkeys the upshift is larger
      than the radius of the fovea. Hence, if the background is dim, the eyes are
      positioned during fixation so that the target does not fall on the fovea. The
      size of the upshift remains almost unchanged while the eyes fixate at different
      orbital positions; thus the upshift is not caused by orbital mechanics. The
      upshift clearly is present even at the first days of training, but with
      additional training in fixation with dark background, the upshift increases in
      size. The upshift rotates with the head. The upshift increases gradually with
      decreasing levels of background luminosity. Luminosity, not visual contrast, is
      indeed the primary variable determining the size of the upshift. The contribution
      of a unit area of the retina to the upshift decreases as inverse square root of
      distance from the target; therefore, it is the perifoveal region of the retina
      that mostly contributes to the upshift, while the far periphery has little
      influence. The upshift can be induced or be canceled in the midst of a fixation
      by changing the background illumination; hence, the upshift is indeed an
      attribute of the fixation control system. Finally, the fixation-upshift studied
      here is different from a previously reported upshift of the endpoints of memory
      guided saccades with respect to their target locations. These two types of
      upshift add up to each other. In discussing the function of the upshift, we note
      a possible morphological analogue with the retinal rod distribution. The upshift
      moves the line of gaze to a point intermediate between the fovea and the "dorsal
      rod peak." The upshift thus may improve visual acuity in scotopic conditions. The
      brain structure in which the upshift is generated must be involved in both ocular
      control and visual sensation. We consider several possibilities, of which we
      regard as the most likely the cerebellum and superior colliculus.

PMID- 9582244
TI  - Electrophysiological properties of human astrocytic tumor cells In situ: enigma
      of spiking glial cells.
AB  - To better understand physiological changes that accompany the neoplastic
      transition of astrocytes to become astrocytoma cells, we studied biopsies of low
      grade, pilocytic astrocytomas. This group of tumors is most prevalent in children
      and the tumor cells maintain most antigenic features typical of astrocytes.
      Astrocytoma cells were studied with the use of whole cell patch-clamp recordings
      in acute biopsy slices from 4-mo- to 14-yr-old pediatric patients. Recordings
      from 53 cells in six cases of low-grade astrocytomas were compared to either
      noncancerous peritumoral astrocytes or astrocytes obtained from other surgeries.
      Astrocytoma cells almost exclusively displayed slowly activating, sustained,
      tetraethylammonium (TEA)-sensitive outward potassium currents (delayed rectifying
      potassium currents; IDR) and transient, tetrodotoxin (TTX)-sensitive sodium
      currents (INa). By contrast, comparison glial cells from peritumoral regions or
      other surgeries showed IDR and INa, but in addition these cells also expressed
      transient "A"-type K+ currents and inwardly rectifying K+ currents (IIR), both of
      which were absent in astrocytoma cells. IIR constituted the predominant
      conductance in comparison astrocytes and was responsible for a high-resting K+
      conductance in these cells. Voltage-activated Na+ currents were observed in 37 of
      53 astrocytoma cells. Na+ current densities in astrocytoma cells, on average,
      were three- to fivefold larger than in comparison astrocytes. Astrocytoma cells
      expressing INa could be induced to generate slow action potential-like responses
      (spikes) by current injections. The threshold for generating such spikes was -34
      mV (from a holding potential of -70 mV). The spike amplitude and time width were
      52.5 mV and 12 ms, respectively. No spikes could be elicited in comparison
      astrocytes, although some of them expressed Na+ currents of similar size.
      Comparison of astrocytes to astrocytoma cells suggests that the apparent lack of
      IIR, which leads to high-input resistance (>500 MOmega), allows glioma cells to
      be sufficiently depolarized to generate Na+ spikes, whereas the high resting K+
      conductance in astrocytes prevents their depolarization and thus generation of
      spikes. Consistent with this notion, Na+ spikes could be induced in spinal cord
      astrocytes in culture when IIR was experimentally blocked by 10 microM Ba2+,
      suggesting that the absence of IIR in astrocytoma cells is primarily responsible
      for the unusual spiking behavior seen in these glial tumor cells. It is unlikely
      that such glial spikes ever occur in vivo.

PMID- 9582245
TI  - Effect of motion contrast on human cortical responses to moving stimuli.
AB  - The cortical areas activated by motion-defined contours were studied in humans
      using positron emission tomography (PET). Subjects observed four types of random
      dot fields, displayed through a 21 degrees diam aperture: unidirectional motion
      of a translating dot field, motion in opposing directions of two superimposed
      translating fields, motion in opposing directions of dots in contiguous spatial
      regions (motion contrast), producing a square wave grating defined by motion, and
      luminance variation of stationary dots in contiguous spatial regions, producing a
      square wave grating defined by luminance. Relative to a static dot field, the
      unidirectional motion condition activated areas previously described, including
      areas 17/18, lateral temporal-occipital-parietal cortex (MT/MST), and the
      superior temporal sulcus. Motion-defined gratings increased the activation of
      areas 17/18 and MT/MST, but not the superior temporal sulcus, and added more
      dorsal areas in the cuneus, roughly corresponding to V3/V3a, and ventral areas in
      the lingual gyrus/collateral sulcus, roughly corresponding to V2/VP. Luminance
      defined gratings, relative to a static dot field, activated areas 17/18, regions
      in the dorsal cuneus similar to those activated by motion defined gratings, and a
      region near the left collateral sulcus, slightly lateral to the motion grating
      activation. They also activated a region in the right fusiform gyrus that was
      more weakly activated by the motion grating. These results indicate that adding
      motion contrast to large moving fields increases activity in areas 17/18 and
      MT/MST and adds both dorsal and ventral regions that are similar for motion and
      luminance defined contours.

PMID- 9582246
TI  - NMDA receptor-mediated oscillatory activity in the neonatal rat spinal cord is
      serotonin dependent.
AB  - The effect of serotonin (5-HT) receptor blockade on rhythmic network activity and
      on N-methyl--aspartate (NMDA) receptor-induced membrane voltage oscillations was
      examined using an in vitro neonatal rat spinal cord preparation.
      Pharmacologically induced rhythmic hindlimb activity, monitored via flexor and
      extensor electroneurograms or ventral root recordings, was abolished by 5-HT
      receptor antagonists. Intrinsic motoneuronal voltage oscillations, induced by
      NMDA in the presence of tetrodotoxin (TTX), either were abolished completely or
      transformed to long-lasting voltage shifts by 5-HT receptor antagonists.
      Conversely, 5-HT application facilitated the expression of NMDA-receptor-mediated
      rhythmic voltage oscillations. The results suggest that an interplay between 5-HT
      and NMDA receptor actions may be critical for the production of rhythmic motor
      behavior in the mammalian spinal cord, both at the network and single cell level.

PMID- 9582247
TI  - Temporal integration can readily switch between sublinear and supralinear
      summation.
AB  - Temporal summation at dendrites of cultured rat hippocampal neurons was examined
      as a function of the interval separating two dendritic inputs. A novel method
      that relies on single-mode optical fibers to achieve rapid photorelease of
      glutamate was developed. Dendritic excitation achieved with this approach
      resembles that associated with miniature excitatory postsynaptic currents
      (mEPSCs), but the strengths, sites, and timing of the inputs can be precisely
      controlled. Dendritic summation deviated markedly from behavior predicted by
      passive cable theory. Subthreshold temporal summation varied as a triphasic
      function of the interpulse interval. As the interpulse interval decreased, local
      dendritic Na+ conductances were recruited to generate a marked transition from
      sublinear to supralinear summation. These results suggest that active dendritic
      conductances acting in concert with passive cable properties may serve to boost
      coincident synaptic inputs and attenuate noncoincident inputs.

PMID- 9582248
TI  - Change in motor plan, without a change in the spatial locus of attention,
      modulates activity in posterior parietal cortex.
AB  - The lateral intraparietal area (LIP) of macaque monkey, and a parietal reach
      region (PRR) medial and posterior to LIP, code the intention to make visually
      guided eye and arm movements, respectively. We studied the effect of changing the
      motor plan, without changing the locus of attention, on single neurons in these
      two areas. A central target was fixated while one or two sequential flashes
      occurred in the periphery. The first appeared either within the response field of
      the neuron being recorded or else on the opposite side of the fixation point.
      Animals planned a saccade (red flash) or reach (green flash) to the flash
      location. In some trials, a second flash 750 ms later could change the motor plan
      but never shifted attention: second flashes always occurred at the same location
      as the preceding first flash. Responses in LIP were larger when a saccade was
      instructed (n = 20 cells), whereas responses in PRR were larger when a reach was
      instructed (n = 17). This motor preference was observed for both first flashes
      and second flashes. In addition, the response to a second flash depended on
      whether it affirmed or countermanded the first flash; second flash responses were
      diminished only in the former case. Control experiments indicated that this
      differential effect was not due to stimulus novelty. These findings support a
      role for posterior parietal cortex in coding specific motor intention and are
      consistent with a possible role in the nonspatial shifting of motor intention.

PMID- 9582249
TI  - Localization of CCK receptors in thalamic reticular neurons: a modeling study.
AB  - In an earlier experimental study, intracellular recording suggested that
      cholecystokinin (CCK) suppresses a K+ conductance in thalamic reticular (RE)
      neurons, yet the reversal potential of the CCK response, revealed using voltage
      clamp, was hyperpolarized significantly relative to the K+ equilibrium potential.
      Here, biophysical models of RE neurons were developed and used to test whether
      suppression of the K+ conductance, gK, can account for the CCK response observed
      in vitro and also to determine the likely site of CCK receptors on RE neurons.
      Suppression of gK in model RE neurons can reproduce the relatively hyperpolarized
      reversal potential of CCK responses found using voltage clamp if the voltage
      clamp becomes less effective at hyperpolarized potentials. Three factors would
      reduce voltage-clamp effectiveness in this model: the nonnegligible series
      resistance of the voltage-clamp electrode, a hyperpolarization-activated mixed
      cation current (Ih) in RE neurons, and the dendritic location of CCK-sensitive K+
      channels. Although suppression of gK in the dendritic compartments of model RE
      neurons simulates both the magnitude and reversal potential of the CCK response,
      suppression of gK in just the somatic compartment of model RE neurons fails to do
      so. Thus the model predicts that CCK should effectively suppress K+ conductance
      RE neuron dendrites and thereby regulate burst firing in RE neurons. This may
      explain the potent effects of CCK on intrathalamic oscillations in vitro.

PMID- 9582250
TI  - Tanycytes present in the adult rat mediobasal hypothalamus support the
      regeneration of monoaminergic axons.
AB  - We have recently shown that tanycytes present in the median eminence (ME)
      constitute a preferential support for the regeneration of lesioned
      neurohypophysial oxytocinergic and vasopressinergic axons. However, although
      tanycytes are particularly abundant in the ME, they are also present along the
      third ventricle wall. This study was thus undertaken to determine whether
      tanycytes present in the mediobasal hypothalamus overlying the ME were also able
      to support the regeneration of the numerous monoaminergic axons innervating this
      region. Using confocal laser scanning microscopy combined with double or triple
      fluorescence immunostaining, we have compared the relationships occurring between
      glial cells and lesioned catecholaminergic and serotonergic axons at the levels
      of surgical cuts placed in the dorsomedial hypothalamus devoid of tanycytes or in
      the ventromedial hypothalamus containing numerous tanycyte processes. In dorsal
      lesions, catecholaminergic and serotonergic transected fibers were found to abut
      onto the scar formed along the surgical cut and composed of closely
      inderdigitating astrocyte processes strongly immunoreactive for both glial
      fibrillary acidic protein (GFAP) and vimentin (VIM). In ventral lesions, the
      lesional scar was composed of GFAP-immunoreactive (IR) and VIM-IR astrocyte
      processes and of VIM-IR but GFAP-negative processes that were identified as
      tanycytic processes. In all the ventral lesions examined, numerous
      catecholaminergic and serotonergic fibers were found to regenerate into the
      surgical cut in association with the VIM-IR, GFAP-negative tanycyte processes. On
      the other hand, such regenerating fibers were never found in scar portions
      containing only GFAP-IR astrocytic structures. These data indicate that, like in
      the ME, tanycytes present in the mediobasal hypothalamus of adult rat provide a
      substrate that favors the regeneration of lesioned axons.

PMID- 9582251
TI  - The effects of NGF and sensory nerve stimulation on collateral sprouting and gene
      expression in adult sensory neurons.
AB  - Collateral sprouting of mature cutaneous nociceptive fibers is regulated by the
      availability of NGF, and the onset of this sprouting can be accelerated by
      electrical stimulation of the intact nerve. To investigate this influence of
      stimulation on NGF-induced sprouting, the thoracic dorsal cutaneous nerves of
      adult rats were exposed and those on the left side of the animals were
      electrically stimulated. NGF was then administered daily for 1-12 days. At 12
      days poststimulation, the extent of nociceptive fibers sprouting was examined by
      an established behavioral mapping technique and was found to have occurred only
      in the NGF-treated animals. The dorsal root ganglia (DRGs) were sampled at
      various times throughout the experiment and processed for in situ hybridization
      to examine mRNA expression of the NGF receptors (p75 and trkA) and GAP-43. As
      well, expression of mRNAs for the neurotrophins NGF, BDNF, and NT-3 was examined.
      p75, trkA, and GAP-43 mRNAs were upregulated in DRGs from the NGF-treated, but
      not the control animals. The combination of stimulation plus NGF resulted in
      these increases being slightly higher than those in the absence of stimulation;
      however, stimulation alone had little effect on the mRNA expression. Examination
      of the neurotrophin mRNAs confirmed the absence of neuronal NGF and NT-3
      expression and the presence of neuronal BDNF mRNA. The NGF treatment resulted in
      the upregulation of BDNF mRNA to peak levels within the first 2 days of
      treatment, although the electrical stimulation had little additional effect.
      These results demonstrate that exogenously supplied NGF itself can elicit
      sprouting from intact cutaneous nociceptive afferents and that electrical
      stimulation further influences the expression of mRNAs involved in the sprouting
      response. While the increases in NGF receptors and GAP-43 mRNA have been shown to
      be associated with collateral sprouting, the role of BDNF is not clear, but may
      be involved in altered sensory processing (i.e., hyperalgesia) that has been
      shown to occur subsequent to NGF administration.

PMID- 9582252
TI  - PCBs reduce long-term potentiation in the CA1 region of rat hippocampus.
AB  - Prenatal exposure to polychlorinated biphenyls (PCBs) has been associated with a
      lower IQ in childhood. We have examined the effects of acute exposure to PCB
      mixtures and two single congeners on synaptic transmission between Schaffer
      collaterals and CA1 neurons of the rat hippocampus as well as posttetanic
      potentiation (PTP), paired pulse facilitation (PPF), and long-term potentiation
      (LTP). PTP and PPF represent transient increases in transmitter release
      immediately after stimulation, while LTP is a measure of long-term changes in
      synaptic plasticity that has been related to learning and memory. LTP, but
      neither PTP nor PPF, was reduced by Aroclor 1016 in a dose-dependent fashion at
      concentrations that had little effect on general synaptic transmission. The more
      highly chlorinated Aroclor 1254 at low concentrations specifically blocked LTP,
      but at higher concentrations also reduced synaptic transmission. The mono-ortho
      PCB congener 2,4,4'-trichlorobiphenyl and the coplanar congener 3,3',4,4'
      tetrachlorobiphenyl also blocked LTP without effect on PTP or PPF. We conclude
      that PCBs selectively impair the process of LTP in CA1 neurons of the
      hippocampus.

PMID- 9582253
TI  - Behavioral effects of 5-HT2C receptor antagonism in the substantia nigra zona
      reticulata of the 6-hydroxydopamine-lesioned rat model of Parkinson's disease.
AB  - Overactivity of the substantia nigra zona reticulata and the medial segment of
      the globus pallidus are responsible for the generation of symptoms in Parkinson's
      disease. Reducing the activity of these regions has been shown to be a viable
      alternative to dopamine replacement in the symptomatic treatment of Parkinson's
      disease. 5-HT2C receptors in the substantia nigra zona reticulata are excitatory.
      In this study we have shown that intracerebral infusion of the selective 5-HT2C
      receptor antagonist SB 206553 (50 nmol) into the substantia nigra zona reticulata
      has an antiparkinsonian action in the 6-hydroxydopamine-lesioned rat model of
      Parkinson's disease. SB 206553 did not affect locomotion when injected into the
      nonparkinsonian substantia nigra. Furthermore, we have demonstrated that systemic
      administration of selective 5-HT2C receptor antagonists SB 200646A (20 mg/kg) and
      SB 206553 (20 mg/kg) can potentiate the antiparkinsonian action of the dopamine
      D2 receptor agonist quinpirole in the 6-hydroxydopamine-lesioned rat. Hence, 5
      HT2C receptor antagonists may be useful adjuncts to dopamine agonists in the
      treatment of Parkinson's disease.

PMID- 9582254
TI  - Adult opossums (Didelphis virginiana) demonstrate near normal locomotion after
      spinal cord transection as neonates.
AB  - When the thoracic spinal cord of the North American opossum (Didelphis
      virginiana) is transected on postnatal day (PD) 5, the site of injury becomes
      bridged by histologically recognizable spinal cord and axons which form major
      long tracts grow through the lesion. In the present study we asked whether
      opossums lesioned on PD5 have normal use of the hindlimbs as adults and, if so,
      whether that use is dependent upon axons which grow through the lesion site. The
      thoracic spinal cord was transected on PD5 and 6 months later, hindlimb function
      was evaluated using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. All
      animals supported their weight with the hindlimbs and used their hindlimbs
      normally during overground locomotion. In some cases, the spinal cord was
      retransected at the original lesion site or just caudal to it 6 months after the
      original transection and paralysis of the hindlimbs ensued. Surprisingly,
      however, these animals gradually recovered some ability to support their weight
      and to step with the hindlimbs. Similar recovery was not seen in animals
      transected only as adults. In order to verify that descending axons which grew
      through the lesion during development were still present in the adult animal,
      opossums subjected to transection of the thoracic cord on PD5 were reoperated and
      Fast blue was injected several segments caudal to the lesion. In all cases,
      neurons were labeled rostral to the lesion in each of the spinal and supraspinal
      nuclei labeled by comparable injections in unlesioned, age-matched controls. The
      results of orthograde tracing studies indicated that axons which grew through the
      lesion innervated areas that were appropriate for them.

PMID- 9582255
TI  - Opioids disrupt Ca2+ homeostasis and induce carbonyl oxyradical production in
      mouse astrocytes in vitro: transient increases and adaptation to sustained
      exposure.
AB  - Pharmacologically distinct subpopulations of astroglia express mu, delta, and/or
      kappa opioid receptors. Activation of mu, delta, or kappa opioid receptors can
      destabilize intracellular calcium ([Ca2+]i) in astrocytes leading to cellular
      hypertrophy and reactive injury. To assess whether acute or sustained opioid
      exposure might adversely affect astroglial function by disrupting Ca2+
      homeostasis or by producing reactive oxygen species, fura-2 and a novel
      fluorescent-tagged biotin-4-amidobenzoic hydrazide reagent, respectively, were
      used to detect [Ca2+]i and carbonyl oxidation products within individual murine
      astrocytes. Acute (3 h) exposure to mu; (H-Tyr-Pro-Phe (N-Me) -D-Pro-NH2; PLO17),
      delta ([D-Pen2, D-Pen5]-enkephalin), and kappa (trans-(+/-)-3, 4-dichloro-N
      methyl-N-[2-(1-pyrr olidinyl) cyclohexyl] benzeneacetamide methanesulfonate;
      U50,488H) opioid agonists caused significant mean increases in [Ca2+]i and in the
      levels of oxidative products in astrocytes. In contrast, following 72 h of
      continuous opioid exposure, [Ca2+]i and carbonyl levels returned to normal,
      irrespective of opioid treatment. These preliminary findings indicate that
      opioids initially destabilize [Ca2+]i and increase reactive oxygen species in
      astrocytes; however, astrocytes later recover and adapt to sustained opioid
      exposure.

PMID- 9582256
TI  - Acute inflammatory response in spinal cord following impact injury.
AB  - Numerous factors are involved in the spread of secondary damage in spinal cord
      after traumatic injury, including ischemia, edema, increased excitatory amino
      acids, and oxidative damage to the tissue from reactive oxygen species.
      Neutrophils and macrophages can produce reactive oxygen species when activated
      and thus may contribute to the lipid peroxidation that is known to occur after
      spinal cord injury. This study examined the rostral-caudal distribution of
      neutrophils and macrophages/microglia at 4, 6, 24, and 48 h after contusion
      injury to the T10 spinal cord of rat (10 g weight, 50 mm drop). Neutrophils were
      located predominantly in necrotic regions, with a time course that peaked at 24 h
      as measured with assays of myeloperoxidase activity (MPO). The sharpest peak of
      MPO activity was localized between 4 mm rostral and caudal to the injury.
      Macrophages/microglia were visualized with antibodies against ED1 and OX-42.
      Numerous cells with a phagocytic morphology were present by 24 h, with a higher
      number by 48 h. These cells were predominantly located within the gray matter and
      dorsal funiculus white matter. The number of cells gradually declined through 6
      mm rostral and caudal to the lesion. OX-42 staining also revealed reactive
      microglia with blunt processes, particularly at levels distant to the lesion. The
      number of macrophages/microglia was significantly correlated with the amount of
      tissue damage at each level. Treatments to decrease the inflammatory response are
      likely to be beneficial to recovery of function after traumatic spinal cord
      injury.

PMID- 9582258
TI  - Cultured skin fibroblasts isolated from mice devoid of the prion protein gene
      express major heat shock proteins in response to heat stress.
AB  - Recent evidence has suggested that molecular chaperones participate in the
      conformational change between the normal cellular prion protein (PrPC) and its
      scrapie isoform (PrPSc). To study a role of PrPC in the regulation of expression
      of heat shock proteins (HSPs), a group of molecular chaperones, heat-induced
      expression of major HSPs (HSP105, HSP90alpha, HSP72, HSC70, HSP60, and HSP25) was
      investigated in cultured skin fibroblasts isolated from the mice homogeneous for
      a disrupted PrP gene (PrP-/- mice) by Western blot analysis and
      immunocytochemistry. Two lines of fibroblasts were established and designated SFK
      derived from the PrP-/- mice and SFH derived from the PrP+/+ mice, respectively.
      In both SFK and SFH cells, HSP105, HSP72, and HSP25 were expressed at low levels
      under unstressed conditions but they were induced markedly following exposure to
      heat stress (43 degreesC/20 min) at 3-72 h postrecovery. In both cell types,
      HSC70 and HSP60 were expressed at high levels under unstressed conditions and
      their levels remained unchanged after heat shock treatment. HSP90alpha was
      undetectable in both cell types under any conditions examined. The pattern of
      expression, induction, and subcellular location of HSP105, HSP72, HSC70, HSP60,
      and HSP25 was not significantly different between SFK and SFH cells under
      unstressed and heat-stressed conditions. Furthermore, the levels of constitutive
      expression of HSP105, HSC70, HSP60, and HSP25 were similar between the brain
      tissues isolated from the PrP-/- and PrP+/+ mice. These results indicate that HSP
      induction is not affected by either the existence or the absence of PrPC in the
      cells.

PMID- 9582257
TI  - Neuropharmacological characterization of basal forebrain cholinergic stimulated
      cataplexy in narcoleptic canines.
AB  - Basal forebrain (BF) cholinergic regulation of cataplexy was investigated in
      narcoleptic canines. Specific cholinergic agonists and antagonists, and
      excitatory or inhibitory amino acid neurotransmitter receptor agonists, were
      perfused through microdialysis probes implanted bilaterally in the BF of
      narcoleptic canines. Cataplexy was monitored using the food-elicited cataplexy
      test (FECT) and recordings of electroencephalogram, electrooculogram, and
      electromyogram. In narcoleptic canines, carbachol and oxotremorine (10(-5)-10(-3)
      M), but not McN-A-343 or nicotine (10(-4)-10(-3) M), produced a dose-dependent
      increase in cataplexy. In addition, N-methyl-d-aspartate (10(-4)-10(-3) M) and
      kainic acid (10(-5)-10(-4) M) did not have any effects, while muscimol (10(-3) M)
      produced a weak (P < 0.10) increase in cataplexy. In control canines, carbachol
      (10(-5)-10(-3) M), but not oxotremorine (10(-4)-10(-3) M), produced muscle atonia
      after the highest concentration in one of three animals. Carbachol (10(-3) M)
      induced cataplexy in narcoleptic canines was blocked by equimolar perfusion with
      the muscarinic antagonists atropine, gallamine, and 4-DAMP but not pirenzepine.
      These findings indicate that carbachol-stimulated cataplexy in the BF of
      narcoleptic canines is mediated by M2, and perhaps M3, muscarinic receptors. The
      release of acetylcholine in the BF was also examined during FECT and non-FECT
      behavioral stimulation in narcoleptic and control canines. A significant increase
      in acetylcholine release was found in both narcoleptic and control BF during FECT
      stimulation. In contrast, simple motor activity and feeding, approximating that
      which occurs during an FECT, did not affect acetylcholine release in the BF of
      narcoleptic canines. These findings indicate that BF acetylcholine release is
      enhanced during learned emotion/reward associated behaviors in canines.

PMID- 9582259
TI  - Effect of spinal cord injury on the permeability of the blood-brain and blood
      spinal cord barriers to the neurotropin PACAP.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to be a
      potent neurotropin. Because PACAP crosses the blood-brain barrier (BBB) by
      peptide transport system (PTS)-6, it can exert its neurotropic effects even when
      given peripherally. Recent studies have shown that the activity of BBB
      transporters of peptides and regulatory proteins can be affected by
      pathophysiological events, including spinal cord injury. We, therefore,
      determined whether PTS-6 is affected by spinal cord injury. We found that
      radioactively iodinated PACAP was taken up by brain and by all regions of the
      spinal cord. PTS-6 activity was demonstrable in the brain and the cervical and
      thoracic regions of the spinal cord. Spinal cord transection had widespread and
      long-lasting effects throughout the CNS on PTS-6 activity. The most dramatic
      effect was an anatomically descending decrease of PTS-6 activity that began in
      the brain immediately after injury. Later, beginning on day 7 after injury, PTS-6
      activity was increased throughout the CNS. These effects on PTS-6 were unrelated
      to the negligible disruption of barrier function by the injury. We conclude that
      spinal cord injury results in responses that are regionally and temporally unique
      to PTS-6 and could affect the delivery of blood-borne PACAP to the CNS.

PMID- 9582260
TI  - A role for the bilateral involvement of perirhinal cortex in generalized kindled
      seizure expression.
AB  - The perirhinal cortex (PRh) has been suggested as a substrate for the expression
      of generalized clonic seizures in the late stages of kindling development (stages
      4-5). Using the induction of Fos as a marker of neuronal activation, the PRh
      region was investigated after kindling or nonkindling electrical stimulation.
      Nonkindling electrical stimulation of the PRh elicited stimulus-locked behaviors,
      without afterdischarge. These behaviors were characterized by rearing and
      bilateral forelimb clonus which were terminated upon electrical stimulus offset
      in half of the rats displaying this behavior (with the other half expressing self
      sustained seizures). In these animals, Fos immunoreactivity was found throughout
      neocortical and subcortical structures in the hemisphere ipsilateral to the
      stimulating electrode. By contrast, Fos-immunoreactivity in the contralateral
      hemisphere was localized primarily in the PRh and frontal motor cortex. Likewise,
      similar patterns of Fos immunoreactivity were observed in both hemispheres of
      rats following kindling to one generalized clonic seizure from several limbic and
      paleocortical structures. These results suggest that the bilateral involvement of
      the PRh is critical in producing the bilateral behaviors associated with
      generalized clonic seizure expression. In support of this interpretation,
      infusion of 3 M KCl directly into the contralateral PRh of rats kindled to a
      single stage 4-5 (generalized clonic) seizure from the ipsilateral amygdala
      reduced seizure manifestations from a generalized clonic seizure (stage 4-5) to a
      unilateral clonic seizure (stage 3) without affecting measures of focal
      excitability. Taken together, these data indicate a role for the bilateral
      involvement of the PRh in generalized clonic seizure expression whether evoked
      from the naive or kindled state. These results further indicate that bilateral
      behaviors require the bilateral involvement of the structures necessary for the
      expression of these behaviors.

PMID- 9582262
TI  - Seventh international symposium on neural regeneration 
AB  - Copyright

PMID- 9582261
TI  - Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1.
AB  - Recent evidence points to a role of cytokines like tumor necrosis factor-alpha
      (TNF) in the generation of hyperalgesia not only in inflammatory, but also in
      neuropathic pain. We used the model of chronic constrictive injury (CCI) of one
      sciatic nerve in the mouse to investigate which of the two known TNF receptors is
      involved in the process that leads to hyperalgesia after nerve injury.
      Neutralizing antibodies to TNF, to the TNF receptor 1 (TNFR1), and to the TNF
      receptor 2 (TNFR2) were administered by epineurial injection once daily to mice
      with CCI. Testing of the animals' hind paws with thermal and innocuous mechanical
      stimuli revealed a reduction in thermal hyperalgesia and mechanical allodynia in
      mice treated with neutralizing antibodies to TNF and to TNFR1. Neutralizing
      antibodies to TNFR2 had no effect. We conclude that TNFR1, but not TNFR2, is
      mediating thermal hyperalgesia and mechanical allodynia after nerve injury.

PMID- 9582263
TI  - International symposium on spinal cord injury and repair 
AB  - Copyright

PMID- 9582265
TI  - Transport into and out of the cell nucleus.

PMID- 9582266
TI  - Nuclear export of cyclin B1 and its possible role in the DNA damage-induced G2
      checkpoint.
AB  - M-phase-promoting factor (MPF), a complex of cdc2 and a B-type cyclin, is a key
      regulator of the G2/M cell cycle transition. Cyclin B1 accumulates in the
      cytoplasm through S and G2 phases and translocates to the nucleus during
      prophase. We show here that cytoplasmic localization of cyclin B1 during
      interphase is directed by its nuclear export signal (NES)-dependent transport
      mechanism. Treatment of HeLa cells with leptomycin B (LMB), a specific inhibitor
      of the NES-dependent transport, resulted in nuclear accumulation of cyclin B1 in
      G2 phase. Disruption of an NES which has been identified in cyclin B1 here
      abolished the nuclear export of this protein, and consequently the NES-disrupted
      cyclin B1 when expressed in cells accumulated in the nucleus. Moreover, we show
      that expression of the NES-disrupted cyclin B1 or LMB treatment of the cells is
      able to override the DNA damage-induced G2 checkpoint when combined with caffeine
      treatment. These results suggest a role of nuclear exclusion of cyclin B1 in the
      DNA damage-induced G2 checkpoint.

PMID- 9582267
TI  - p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits
      cell growth: suppression by BAG-1.
AB  - The Drosophila seven in absentia (sina) gene is required for R7 photoreceptor
      cell formation during Drosophila eye development, where it functions within the
      Ras/Raf pathway and targets other proteins for degradation via associations with
      a ubiquitin-conjugating enzyme. Recently, a mammalian sina homologue was reported
      to be a p53-inducible gene in a myeloid leukemia cell line. To explore the
      function of human SINA-homologous (Siah) proteins, expression plasmids encoding
      Siah-1A were transiently transfected into 293 epithelial cells and GM701
      fibroblast cells, resulting in growth arrest without induction of apoptosis. We
      discovered that BAG-1, a ubiquitin-like Hsp70/Hsc70-regulating protein, is a
      negative regulator of Siah-1A. Siah-1A was identified as a BAG-1-binding protein
      via yeast two-hybrid methods. Specific interaction of BAG-1 with Siah-1A was also
      demonstrated by in vitro binding experiments using glutathione S-transferase
      fusion proteins and co-immunoprecipitation studies. Siah-1A-induced growth arrest
      in 293 and GM701 cells was abolished by co-transfection of wild-type BAG-1 with
      Siah-1A but not by a C-terminal deletion mutant of BAG-1 that fails to bind Siah
      1A. Over-expression of BAG-1 significantly inhibited p53-induced growth arrest in
      293 cells without preventing p53 transactivation of reporter gene plasmids. BAG-1
      also prevented growth arrest following UV-irradiation-induced genotoxic injury
      without interfering with accumulation of p53 protein or p21(waf-1) expression.
      BAG-1 functions downstream of p53-induced gene expression to inhibit p53-mediated
      suppression of cell growth, presumably by suppressing the actions of Siah-1A. We
      suggest that Siah-1A may be an important mediator of p53-dependent cell-cycle
      arrest and demonstrate that Siah-1A is directly inhibited by BAG-1.

PMID- 9582268
TI  - Nine hydrophobic side chains are key determinants of the thermodynamic stability
      and oligomerization status of tumour suppressor p53 tetramerization domain.
AB  - The contribution of almost each amino acid side chain to the thermodynamic
      stability of the tetramerization domain (residues 326-353) of human p53 has been
      quantitated using 25 mutants with single-residue truncations to alanine (or
      glycine). Truncation of either Leu344 or Leu348 buried at the tetramer interface,
      but not of any other residue, led to the formation of dimers of moderate
      stability (8-9 kcal/mol of dimer) instead of tetramers. One-third of the
      substitutions were moderately destabilizing (<3.9 kcal/mol of tetramer).
      Truncations of Arg333, Asn345 or Glu349 involved in intermonomer hydrogen bonds,
      Ala347 at the tetramer interface or Thr329 were more destabilizing (4.1-5.7
      kcal/mol). Strongly destabilizing (8.8- 11.7 kcal/mol) substitutions included
      those of Met340 at the tetramer interface and Phe328, Arg337 and Phe338 involved
      peripherally in the hydrophobic core. Truncation of any of the three residues
      involved centrally in the hydrophobic core of each primary dimer either prevented
      folding (Ile332) or allowed folding only at high protein concentration or low
      temperature (Leu330 and Phe341). Nine hydrophobic residues per monomer constitute
      critical determinants for the stability and oligomerization status of this p53
      domain.

PMID- 9582269
TI  - Degradation signals for ubiquitin system proteolysis in Saccharomyces cerevisiae.
AB  - Combinations of different ubiquitin-conjugating (Ubc) enzymes and other factors
      constitute subsidiary pathways of the ubiquitin system, each of which
      ubiquitinates a specific subset of proteins. There is evidence that certain
      sequence elements or structural motifs of target proteins are degradation signals
      which mark them for ubiquitination by a particular branch of the ubiquitin system
      and for subsequent degradation. Our aim was to devise a way of searching
      systematically for degradation signals and to determine to which ubiquitin system
      subpathways they direct the proteins. We have constructed two reporter gene
      libraries based on the lacZ or URA3 genes which, in Saccharomyces cerevisiae,
      express fusion proteins with a wide variety of C-terminal extensions. From these,
      we have isolated clones producing unstable fusion proteins which are stabilized
      in various ubc mutants. Among these are 10 clones whose products are stabilized
      in ubc6, ubc7 or ubc6ubc7 double mutants. The C-terminal extensions of these
      clones, which vary in length from 16 to 50 amino acid residues, are presumed to
      contain degradation signals channeling proteins for degradation via the UBC6
      and/or UBC7 subpathways of the ubiquitin system. Some of these C-terminal tails
      share similar sequence motifs, and a feature common to almost all of these
      sequences is a highly hydrophobic region such as is usually located inside
      globular proteins or inserted into membranes.

PMID- 9582270
TI  - Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility
      of Shigella flexneri.
AB  - Shigella, the causative agent of bacillary dysentery, is capable of directing its
      own movement in the cytoplasm of infected epithelial cells. The bacterial surface
      protein VirG recruits host components mediating actin polymerization, which is
      thought to serve as the propulsive force. Here, we show that neural Wiskott
      Aldrich syndrome protein (N-WASP), which is a critical target for filopodium
      formation downstream of Cdc42, is required for assembly of the actin tail
      generated by intracellular S.flexneri. N-WASP accumulates at the front of the
      actin tail and is capable of interacting with VirG in vitro and in vivo, a
      phenomenon that is not observed in intracellular Listeria monocytogenes. The
      verprolin-homology region in N-WASP was required for binding to the glycine-rich
      repeats domain of VirG, an essential domain for recruitment of F-actin on
      intracellular S.flexneri. Overexpression of a dominant-negative N-WASP mutant
      greatly inhibited formation of the actin tail by intracellular S.flexneri.
      Furthermore, depletion of N-WASP from Xenopus egg extracts shut off Shigella
      actin tail assembly, and this was restored upon addition of N-WASP protein,
      suggesting that N-WASP is a critical host factor for the assembly of the actin
      tail by intracellular Shigella.

PMID- 9582272
TI  - Functional properties of the ryanodine receptor type 3 (RyR3) Ca2+ release
      channel.
AB  - Single-channel analysis of sarcoplasmic reticulum vesicles prepared from
      diaphragm muscle, which contains both RyR1 and RyR3 isoforms, revealed the
      presence of two functionally distinct ryanodine receptor calcium release
      channels. In addition to channels with properties typical of RyR1 channels, a
      second population of ryanodine-sensitive channels with properties distinct from
      those of RyR1 channels was observed. The novel channels displayed close-to-zero
      open-probability at nanomolar Ca2+ concentrations in the presence of 1 mM ATP,
      but were shifted to the open conformation by increasing Ca2+ to micromolar levels
      and were not inhibited at higher Ca2+ concentrations. These novel channels were
      sensitive to the stimulatory effects of cyclic adenosine 5'-diphosphoribose
      (cADPR). Detection of this second population of RyR channels in lipid bilayers
      was always associated with the presence of the RyR3 isoform in muscle
      preparations used for single-channel measurements and was abrogated by the
      knockout of the RyR3 gene in mice. Based on the above, we associated the novel
      population of channels with the RyR3 isoform of Ca2+ release channels. The
      functional properties of the RyR3 channels are in agreement with a potential
      qualitative contribution of this channel to Ca2+ release in skeletal muscle and
      in other tissues.

PMID- 9582271
TI  - The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate
      trafficking of class I MHC complexes.
AB  - Nef, a regulatory protein of human and simian immunodeficiency viruses,
      downregulates cell surface expression of both class I MHC and CD4 molecules in T
      cells by accelerating their endocytosis. Fibroblasts were used to study
      alterations in the traffic of class I MHC complexes induced by Nef. We found that
      Nef downregulates class I MHC complexes by a novel mechanism involving the
      accumulation of endocytosed class I MHC in the trans-Golgi, where it colocalizes
      with the adaptor protein-1 complex (AP-1). This effect of Nef on class I MHC
      traffic requires the SH3 domain-binding surface and a cluster of acidic amino
      acid residues in Nef, both of which are also required for Nef to downregulate
      class I MHC surface expression and to alter signal transduction in T cells.
      Downregulation of class I MHC complexes from the surface of T cells also requires
      a tyrosine residue in the cytoplasmic domain of the class I MHC heavy chain
      molecule. The requirement of the same surfaces of the Nef molecule for
      downregulation of surface class I MHC complexes in T cells and for their
      accumulation in the trans-Golgi of fibroblasts indicates that the two effects of
      Nef involve similar interactions with the host cell machinery and involve a
      molecular mechanism regulating class I MHC traffic that is common for both of
      these cell types. Interestingly, the downregulation of class I MHC does not
      require the ability of Nef to colocalize with the adaptor protein-2 complex (AP
      2). We showed previously that the ability of Nef to colocalize with AP-2
      correlates with the ability of Nef to downregulate CD4 expression. Our
      observations indicate that Nef downregulates class I MHC and CD4 surface
      expression via different interactions with the protein sorting machinery, and
      link the sorting and signal transduction machineries in the regulation of class I
      MHC surface expression by Nef.

PMID- 9582273
TI  - Identification of BCAR3 by a random search for genes involved in antiestrogen
      resistance of human breast cancer cells.
AB  - The antiestrogen tamoxifen is important in the treatment of hormone-dependent
      breast cancer, although development of resistance is inevitable. To unravel the
      molecular mechanisms of antiestrogen resistance, a search for involved genes was
      initiated. Retrovirus-mediated insertional mutagenesis was applied to human ZR-75
      1 breast cancer cells. Infected cells were subjected to tamoxifen selection and a
      panel of resistant cell clones was established. Screening for a common
      integration site resulted in the identification of a novel gene designated BCAR3.
      Transfer of this locus by cell fusion or transfection of the BCAR3 cDNA to ZR75-1
      and MCF-7 cells induces antiestrogen resistance. BCAR3 represents a putative SH2
      domain-containing protein and is partly homologous to the cell division cycle
      protein CDC48.

PMID- 9582274
TI  - Evidence that the RdeA protein is a component of a multistep phosphorelay
      modulating rate of development in Dictyostelium.
AB  - We have isolated an insertional mutant of Dictyostelium discoideum that
      aggregated rapidly and formed spores and stalk cells within 14 h of development
      instead of the normal 24 h. We have shown by parasexual genetics that the
      insertion is in the rdeA locus and have cloned the gene. It encodes a predicted
      28 kDa protein (RdeA) that is enriched in charged residues and is very
      hydrophilic. Constructs with the DNA for the c-Myc epitope or for the green
      fluorescent protein indicate that RdeA is not compartmentalized. RdeA displays
      homology around a histidine residue at amino acid 65 with members of the H2
      module family of phosphotransferases that participate in multistep phosphoryl
      relays. Replacement of this histidine rendered the protein inactive. The mutant
      is complemented by transformation with the Ypd1 gene of Saccharomyces cerevisiae,
      itself an H2 module protein. We propose that RdeA is part of a multistep
      phosphorelay system that modulates the rate of development.

PMID- 9582275
TI  - Interferon-gamma expression by Th1 effector T cells mediated by the p38 MAP
      kinase signaling pathway.
AB  - Signal transduction via MAP kinase pathways plays a key role in a variety of
      cellular responses, including growth factor-induced proliferation,
      differentiation and cell death. In mammalian cells, p38 MAP kinase can be
      activated by multiple stimuli, such as pro-inflammatory cytokines and
      environmental stress. Although p38 MAP kinase is implicated in the control of
      inflammatory responses, the molecular mechanisms remain unclear. Upon activation,
      CD4+ T cells differentiate into Th2 cells, which potentiate the humoral immune
      response or pro-inflammatory Th1 cells. Here, we show that pyridinyl imidazole
      compounds (specific inhibitors of p38 MAP kinase) block the production of
      interferon-gamma (IFNgamma) by Th1 cells without affecting IL-4 production by Th2
      cells. These drugs also inhibit transcription driven by the IFNgamma promoter. In
      transgenic mice, inhibition of the p38 MAP kinase pathway by the expression of
      dominant-negative p38 MAP kinase results in selective impairment of Th1
      responses. In contrast, activation of the p38 MAP kinase pathway by the
      expression of constitutivelyactivated MAP kinase kinase 6 in transgenic mice
      caused increased production of IFNgamma during the differentiation and activation
      of Th1 cells. Together, these data demonstrate that the p38 MAP kinase is
      relevant for Th1 cells, not Th2 cells, and that inhibition of p38 MAP kinase
      represents a possible site of therapeutic intervention in diseases where a
      predominant Th1 immune response leads to a pathological outcome. Moreover, our
      study provides an additional mechanism by which the p38 MAP kinase pathway
      controls inflammatory responses.

PMID- 9582276
TI  - Sphingosine kinase-mediated Ca2+ signalling by G-protein-coupled receptors.
AB  - Formation of inositol 1,4,5-trisphosphate (IP3) by phospholipase C (PLC) with
      subsequent release of Ca2+ from intracellular stores, is one of the major Ca2+
      signalling pathways triggered by G-protein-coupled receptors (GPCRs). However, in
      a large number of cellular systems, Ca2+ mobilization by GPCRs apparently occurs
      independently of the PLC-IP3 pathway, mediated by an as yet unknown mechanism.
      The present study investigated whether sphingosine kinase activation, leading to
      production of sphingosine-1-phosphate (SPP), is involved in GPCR-mediated Ca2+
      signalling as proposed for platelet-derived growth factor and FcepsilonRI antigen
      receptors. Inhibition of sphingosine kinase by DL-threo-dihydrosphingosine and
      N,N-dimethylsphingosine markedly inhibited [Ca2+]i increases elicited by m2 and
      m3 muscarinic acetylcholine receptors (mAChRs) expressed in HEK-293 cells without
      affecting mAChR-induced PLC stimulation. Activation of mAChRs rapidly and
      transiently stimulated production of SPP in HEK-293 cells. Finally, intracellular
      injection of SPP induced a rapid and transient Ca2+ mobilization in HEK-293 cells
      which was not antagonized by heparin. We conclude that mAChRs utilize the
      sphingosine kinase-SPP pathway in addition to PLC-IP3 to mediate Ca2+
      mobilization. As Ca2+ signalling by various, but not all, GPCRs in different cell
      types was likewise attenuated by the sphingosine kinase inhibitors, we suggest a
      general role for sphingosine kinase, besides PLC, in mediation of GPCR-induced
      Ca2+ signalling.

PMID- 9582277
TI  - An intersection of the cAMP/PKA and two-component signal transduction systems in
      Dictyostelium.
AB  - Terminal differentiation of both stalk and spore cells in Dictyostelium can be
      triggered by activation of cAMP-dependent protein kinase (PKA). A screen for
      mutants where stalk and spore cells mature in isolation produced three genes
      which may act as negative regulators of PKA: rdeC (encoding the PKA regulatory
      subunit), regA and rdeA. The biochemical properties of RegA were studied in
      detail. One domain is a cAMP phosphodiesterase (Km approximately 5 microM); the
      other is homologous to response regulators (RRs) of two-component signal
      transduction systems. It can accept phosphate from acetyl phosphate in a reaction
      typical of RRs, with transfer dependent on Asp212, the predicted phosphoacceptor.
      RegA phosphodiesterase activity is stimulated up to 8-fold by the phosphodonor
      phosphoramidate, with stimulation again dependent on Asp212. This indicates that
      phosphorylation of the RR domain activates the phosphodiesterase domain.
      Overexpression of the RR domain in wild-type cells phenocopies a regA null. We
      interpret this dominant-negative effect as due to a diversion of the normal flow
      of phosphates from RegA, thus preventing its activation. Mutation of rdeA is
      known to produce elevated cAMP levels. We propose that cAMP breakdown is
      controlled by a phosphorelay system which activates RegA, and may include RdeA.
      Cell maturation should be triggered when this system is inhibited.

PMID- 9582279
TI  - Cloning and functional characterization of PTRF, a novel protein which induces
      dissociation of paused ternary transcription complexes.
AB  - Termination of transcription by RNA polymerase I (Pol I) is a two-step process
      which involves pausing of elongating transcription complexes and release of both
      pre-rRNA and Pol I from the template. In mouse, pausing of elongation complexes
      is mediated by the transcription termination factor TTF-I bound to the 'Sal box'
      terminator downstream of the rDNA transcription unit. Dissociation of paused
      ternary complexes requires a cellular factor, termed PTRF for Pol I and
      transcript release factor. Here we describe the molecular cloning of a cDNA
      corresponding to murine PTRF. Recombinant PTRF is capable of dissociating ternary
      Pol I transcription complexes in vitro as revealed by release of both Pol I and
      nascent transcripts from the template. Consistent with its function in
      transcription termination, PTRF interacts with both TTF-I and Pol I. Moreover, we
      demonstrate specific binding of PTRF to transcripts containing the 3' end of pre
      rRNA. Substitution of 3'-terminal uridylates by guanine residues abolishes PTRF
      binding and impairs release activity. The results reveal a network of protein
      protein and protein-nucleic acid interactions that governs termination of Pol I
      transcription.

PMID- 9582278
TI  - Embryonic lethality and liver degeneration in mice lacking the metal-responsive
      transcriptional activator MTF-1.
AB  - We have shown previously that the heavy metal-responsive transcriptional
      activator MTF-1 regulates the basal and heavy metal-induced expression of
      metallothioneins. To investigate the physiological function of MTF-1, we
      generated null mutant mice by targeted gene disruption. Embryos lacking MTF-1 die
      in utero at approximately day 14 of gestation. They show impaired development of
      hepatocytes and, at later stages, liver decay and generalized edema. MTF-1(-/-)
      embryos fail to transcribe metallothionein I and II genes, and also show
      diminished transcripts of the gene which encodes the heavy-chain subunit of the
      gamma-glutamylcysteine synthetase, a key enzyme for glutathione biosynthesis.
      Metallothionein and glutathione are involved in heavy metal homeostasis and
      detoxification processes, such as scavenging reactive oxygen intermediates.
      Accordingly, primary mouse embryo fibroblasts lacking MTF-1 show increased
      susceptibility to the cytotoxic effects of cadmium or hydrogen peroxide. Thus,
      MTF-1 may help to control metal homeostasis and probably cellular redox state,
      especially during liver development. We also note that the MTF-1 null mutant
      phenotype bears some similarity to those of two other regulators of cellular
      stress response, namely c-Jun and NF-kappaB (p65/RelA).

PMID- 9582281
TI  - Regulation of crp transcription by oscillation between distinct nucleoprotein
      complexes.
AB  - FIS belongs to the group of small abundant DNA-binding proteins of Escherichia
      coli. We recently demonstrated that, in vivo, FIS regulates the expression of
      several genes needed for catabolism of sugars and nucleic acids, a majority of
      which are also transcriptionally regulated by cAMP-cAMP-receptor protein (CRP)
      complex. Here we provide evidence that FIS represses transcription of the crp
      gene both in vivo and in vitro. Employing crp promoter-lacZ fusions, we
      demonstrate that both FIS and cAMP-CRP are required to keep the crp promoter in a
      repressed state. We have identified in the crp promoter other transcription
      initiation sites which are located 73, 79 and 80 bp downstream from the
      previously mapped start site. Two CRP- and several FIS-binding sites with
      different affinities are located in the crp promoter region, one of them
      overlapping the downstream transcription initiation sites. We show that
      initiation of transcription at the crp promoter is affected by the composition of
      nucleoprotein complexes resulting from the outcome of competition between
      proteins for overlapping binding sites. Our results suggest that the control of
      crp transcription is achieved by oscillation in the composition of these
      regulatory nucleoprotein complexes in response to the physiological state of the
      cell.

PMID- 9582280
TI  - Histone acetylation facilitates RNA polymerase II transcription of the Drosophila
      hsp26 gene in chromatin.
AB  - A number of activators are known to increase transcription by RNA polymerase
      (pol) II through protein acetylation. While the physiological substrates for
      those acetylases are poorly defined, possible targets include general
      transcription factors, activator proteins and histones. Using a cell-free system
      to reconstitute chromatin with increased histone acetylation levels, we directly
      tested for a causal role of histone acetylation in transcription by RNA pol II.
      Chromatin, containing either control or acetylated histones, was reconstituted to
      comparable nucleosome densities and characterized by electron microscopy after
      psoralen cross-linking as well as by in vitro transcription. While H1-containing
      control chromatin severely repressed transcription of our model hsp26 gene,
      highly acetylated chromatin was significantly less repressive. Acetylation of
      histones, and particularly of histone H4, affected transcription at the level of
      initiation. Monitoring the ability of the transcription machinery to associate
      with the promoter in chromatin, we found that heat shock factor, a crucial
      regulator of heat shock gene transcription, profited most from histone
      acetylation. These experiments demonstrate that histone acetylation can modulate
      activator access to their target sites in chromatin, and provide a causal link
      between histone acetylation and enhanced transcription initiation of RNA pol II
      in chromatin.

PMID- 9582282
TI  - The acetyltransferase activity of CBP stimulates transcription.
AB  - The CBP co-activator protein possesses an intrinsic acetyltransferase (AT)
      activity capable of acetylating nucleosomal histones, as well as other proteins
      such as the transcription factors TFIIE and TFIIF. In addition, CBP associates
      with two other TSs, P/CAF and SRC1. We set out to establish whether the intrinsic
      AT activity of CBP contributes to transcriptional activation. We show that a
      region of CBP, encompassing the previously defined histone AT (HAT) domain, can
      stimulate transcription when tethered to a promoter. The stimulatory effect of
      this activation domain shows some promoter preference and is dependent on AT
      activity. Analysis of 14 point mutations reveals a direct correlation between
      CBP's ability to acetylate histones in vitro and to activate transcription in
      vivo. We also find that the HAT domains of CBP and P/CAF share sequence
      similarity. Four conserved motifs are identified, three of which are analogous to
      motifs A, B and D, found in other N-acetyltransferases. The fourth motif, termed
      E, is unique to CBP and P/CAF. Mutagenesis shows that all four motifs in CBP
      contribute to its HAT activity in vitro and its ability to activate transcription
      in vivo. These results demonstrate that the AT activity of CBP is directly
      involved in stimulating gene transcription. The identification of specific HAT
      domain motifs, conserved between CBP and P/CAF, should facilitate the
      identification of other members of this AT family.

PMID- 9582283
TI  - Induction of type III secretion in Shigella flexneri is associated with
      differential control of transcription of genes encoding secreted proteins.
AB  - Shigella, the etiological agent of human bacillary dysentery, invades the colonic
      epithelium where it induces an intense inflammatory response. Entry of Shigella
      into epithelial cells involves a type III secretion machinery, encoded by the mxi
      and spa operons, and the IpaA-D secreted proteins. In this study, we have
      identified secreted proteins of 46 and 60 kDa as the products of virA and
      ipaH9.8, respectively, the latter being a member of the ipaH multigene family.
      Inactivation of virA did not affect entry into epithelial cells. Using lacZ
      transcriptional fusions, we found that transcription of virA and four ipaH genes,
      but not that of the ipaBCDA and mxi operons, was markedly increased during growth
      in the presence of Congo red and in an ipaD mutant, two conditions in which
      secretion through the Mxi-Spa machinery is enhanced. Transcription of the virA
      and ipaH genes was also transiently activated upon entry into epithelial cells.
      These results suggest that transcription of the virA and ipaH genes is regulated
      by the type III secretion machinery and that a regulatory cascade differentially
      controls transcription of genes encoding secreted proteins, some of which, like
      virA, are not required for entry.

PMID- 9582284
TI  - Coupling of signal transduction to alternative pre-mRNA splicing by a composite
      splice regulator.
AB  - Alternative splicing of pre-mRNA is a fundamental mechanism of differential gene
      expression in that it can give rise to functionally distinct proteins from a
      single gene, according to the developmental or physiological state of cells in
      multicellular organisms. In the pre-mRNA of the cell surface molecule CD44, the
      inclusion of up to 10 variant exons (v1-v10) is regulated during development,
      upon activation of lymphocytes and dendritic cells, and during tumour
      progression. Using minigene constructs containing CD44 exon v5, we have
      discovered exonic RNA elements that couple signal transduction to alternative
      splicing. They form a composite splice regulator encompassing an exon recognition
      element and splice silencer elements. Both type of elements are necessary to
      govern cell type-specific inclusion of the exon as well as inducible inclusion in
      T cells after stimulation by concanavalin A, by Ras signalling or after
      activation of protein kinase C by phorbol ester. Inducible splicing does not
      depend on de novo protein synthesis. The coupling of signal transduction to
      alternative splicing by such elements probably represents the mechanism whereby
      splice patterns of genes are established during development and can be changed
      under physiological and pathological conditions.

PMID- 9582285
TI  - A single amino acid substitution in yeast eIF-5A results in mRNA stabilization.
AB  - Most factors known to function in mRNA turnover are not essential for cell
      viability. To identify essential factors, approximately 4000 temperature
      sensitive yeast strains were screened for an increase in the level of the
      unstable CYH2 pre-mRNA. At the non-permissive temperature, five mutants exhibited
      decreased decay rates of the CYH2 pre-mRNA and mRNA, and the STE2, URA5 and PAB1
      mRNAs. Of these, the mutant ts1159 had the most extensive phenotype. Expression
      of the TIF51A gene (encoding eIF-5A) complemented the temperature-sensitive
      growth and mRNA decay phenotypes of ts1159. The tif51A allele was rescued from
      these cells and shown to encode a serine to proline change within a predicted
      alpha-helical segment of the protein. ts1159 also exhibited an approximately 30%
      decrease in protein synthesis at the restrictive temperature. Measurement of
      amino acid incorporation in wild-type cells incubated with increasing amounts of
      cycloheximide demonstrated that a decrease in protein synthesis of this magnitude
      could not account for the full extent of the mRNA decay defects observed in
      ts1159. Interestingly, the ts1159 cells accumulated uncapped mRNAs at the non
      permissive temperature. These results suggest that eIF-5A plays a role in mRNA
      turnover, perhaps acting downstream of decapping.

PMID- 9582286
TI  - The DEAH-box protein PRP22 is an ATPase that mediates ATP-dependent mRNA release
      from the spliceosome and unwinds RNA duplexes.
AB  - Of the proteins required for pre-mRNA splicing, at least four, the DEAH-box
      proteins, are closely related due to the presence of a central 'RNA helicase
      like' region, and extended homology through a large portion of the protein. A
      major unresolved question is the function of these proteins. Indirect evidence
      suggests that several of these proteins are catalysts for important structural
      rearrangements in the spliceosome. However, the mechanism for the proposed
      alterations is presently unknown. We present evidence that PRP22, a DEAH-box
      protein required for mRNA release from the spliceosome, unwinds RNA duplexes in a
      concentration- and ATP-dependent manner. This demonstrates that PRP22 can modify
      RNA structure directly. We also show that the PRP22-dependent release of mRNA
      from the spliceosome is an ATP-dependent process and that recombinant PRP22 is an
      ATPase. Non-hydrolyzable ATP analogs did not substitute for ATP in the RNA
      unwinding reaction, suggesting that ATP hydrolysis is required for this reaction.
      Specific mutation of a putative ATP phosphate-binding motif in the recombinant
      protein eliminated the ATPase and RNA-unwinding capacity. Significantly, these
      data suggest that the DEAH-box proteins act directly on RNA substrates within the
      spliceosome.

PMID- 9582287
TI  - Progression through the spliceosome cycle requires Prp38p function for U4/U6
      snRNA dissociation.
AB  - The elaborate and energy-intensive spliceosome assembly pathway belies the
      seemingly simple chemistry of pre-mRNA splicing. Prp38p was previously identified
      as a protein required in vivo and in vitro for the first pre-mRNA cleavage
      reaction catalyzed by the spliceosome. Here we show that Prp38p is a unique
      component of the U4/U6.U5 tri-small nuclear ribonucleoprotein (snRNP) particle
      and is necessary for an essential step late in spliceosome maturation. Without
      Prp38p activity spliceosomes form, but arrest in a catalytically impaired state.
      Functional spliceosomes shed U4 snRNA before 5' splice-site cleavage. In
      contrast, Prp38p-defective spliceosomes retain U4 snRNA bound to its U6 snRNA
      base-pairing partner. Prp38p is the first tri-snRNP-specific protein shown to be
      dispensable for assembly, but required for conformational changes which lead to
      catalytic activation of the spliceosome.

PMID- 9582288
TI  - The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus
      and its complexes with ATP and asparaginyl-adenylate: the mechanism of
      discrimination between asparagine and aspartic acid.
AB  - The crystal structure of Thermus thermophilus asparaginyl-tRNA synthetase has
      been solved by multiple isomorphous replacement and refined at 2.6 A resolution.
      This is the last of the three class IIb aminoacyl-tRNA synthetase structures to
      be determined. As expected from primary sequence comparisons, there are
      remarkable similarities between the tertiary structures of asparaginyl-tRNA
      synthetase and aspartyl-tRNA synthetase, and most of the active site residues are
      identical except for three key differences. The structure at 2.65 A of
      asparaginyl-tRNA synthetase complexed with a non-hydrolysable analogue of
      asparaginyl-adenylate permits a detailed explanation of how these three
      differences allow each enzyme to discriminate between their respective and very
      similar amino acid substrates, asparagine and aspartic acid. In addition, a
      structure of the complex of asparaginyl-tRNA synthetase with ATP shows exactly
      the same configuration of three divalent cations as previously observed in the
      seryl-tRNA synthetase-ATP complex, showing that this a general feature of class
      II synthetases. The structural similarity of asparaginyl- and aspartyl-tRNA
      synthetases as well as that of both enzymes to the ammonia-dependent asparagine
      synthetase suggests that these three enzymes have evolved relatively recently
      from a common ancestor.

PMID- 9582290
TI  - tRNA splicing.

PMID- 9582289
TI  - Cell cycle modulation of protein-DNA interactions at a human replication origin.
AB  - We followed the variations of protein-DNA interactions occurring in vivo over the
      early firing replication origin located near the human lamin B2 gene, in IMR-90
      cells synchronized in different moments of the cell cycle. In G0 phase cells no
      protection is present; as the cells progress in G1 phase an extended footprint
      covering over 100 bp appears, particularly marked at the G1/S border. As the
      cells enter S phase the protection shrinks to 70 bp and remains unchanged
      throughout this phase. In mitosis the protection totally disappears, only to
      reappear in its extended form as the cells move into the next G1. These
      variations are reminiscent of those corresponding to the formation of the pre-
      and post-replicative complexes described in yeast and Xenopus cells.

PMID- 9582291
TI  - Nitric oxide-induced deamination of cytosine and guanine in deoxynucleosides and
      oligonucleotides.
AB  - The autoxidation of nitric oxide (NO.) forms the nitrosating agent N2O3, which
      can directly damage DNA by deamination of DNA bases following nitrosation of
      their primary amine functionalities. Within the G:C base pair, deamination
      results in the formation of xanthine and uracil, respectively. To determine the
      effect of DNA structure on the deamination of guanine and cytosine, the NO.
      induced deamination rate constants for deoxynucleosides, single- and double
      stranded oligonucleotides, and a G-quartet oligonucleotide were measured.
      Deamination rate constants were determined relative to morpholine using a
      Silastic membrane to deliver NO. at a rate of approximately 10-20 nmol/ml/min for
      60 min, yielding a final concentration of approximately 600-1200 microM NO2-.
      GC/MS analysis revealed formation of nanomolar levels of deamination products
      from millimolar concentrations of deoxynucleosides and oligomers. Deamination
      rate constants for cytosine and guanine in all types of DNA were lower than the
      morpholine nitrosation rate constant by a factor of approximately 10(3)-10(4).
      Xanthine was formed at twice the rate of uracil, and this may have important
      consequences for mechanisms of NO.-induced mutations. Single-stranded oligomers
      were 5 times more reactive than deoxynucleosides toward N2O3. Double-stranded
      oligomers were 10-fold less reactive than single-stranded oligomers, suggesting
      that Watson-Crick base pairing protects DNA from deamination. G-quartet
      structures were also protective, presumably because of hydrogen bonding. These
      results demonstrate that DNA structure is an important factor in determining the
      reactivity of DNA bases with NO.-derived species.

PMID- 9582292
TI  - Monitoring the Gcn4 protein-mediated response in the yeast Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae the GCN4 gene encodes the transcriptional activator
      of the "general control" system of amino acid bioynthesis, a network of at least
      12 different biosynthetic pathways. We characterized the consequences of the
      general control response upon the signal "amino acid starvation" induced by the
      histidine analogue 3-aminotriazole with respect to Gcn4p levels in more detail.
      Therefore, we established test systems to monitor the time course of different
      parameters, including GCN4 mRNA, Gcn4 protein, Gcn4p DNA binding activity, as
      well as Gcn4p transactivation ability. We observed a biphasic response of Gcn4p
      activity in the cell. At first, translation of GCN4 mRNA is induced within 20 min
      after switch to starvation conditions. However, an additional increase in GCN4
      transcript steady state level was observed, leading to an additional second phase
      of GCN4 expression after 3-4 h of starvation. The DNA binding activity of Gcn4p,
      as well as the ability to activate transcription of target genes, correlate with
      the amount of Gcn4 protein in the cell, suggesting that under the tested
      conditions there is no additional regulation of DNA binding or transactivation
      ability of Gcn4p, respectively.

PMID- 9582293
TI  - Disruption of the intracellular sulfhydryl homeostasis by cadmium-induced
      oxidative stress leads to protein thiolation and ubiquitination in neuronal
      cells.
AB  - Cadmium is a potent cell poison known to cause oxidative stress by increasing
      lipid peroxidation and/or by changing intracellular glutathione levels and to
      affect the ubiquitin/ATP-dependent proteolytic pathway. However, the cellular
      mechanisms involved in cadmium toxicity are still not well understood, especially
      in neuronal cells. To investigate the relationship between cadmium-induced
      oxidative stress and the ubiquitin/ATP-dependent pathway, we treated cultures of
      neuronal cells with different concentrations of the metal ion. In addition to
      decreases in glutathione levels, we observed marked increases in protein-mixed
      disulfides (Pr-SSGs) after exposure of HT4 cells (a mouse neuronal cell line) or
      rat primary mesencephalic cultures to Cd2+. The increases in intracellular levels
      of Pr-SSGs were concurrent with increases in the levels of ubiquitinated proteins
      (Ub proteins) when the HT4 cells were subjected to lower (25 microM or less)
      concentrations of cadmium. However, higher concentrations of cadmium (50 microM),
      which were toxic, led to increases in Pr-SSGs but inhibited ubiquitination,
      probably reflecting inhibition of ubiquitinating enzymes. The cadmium-induced
      changes in Pr-SSGs and Ub proteins were not affected when more than 85% of
      intracellular glutathione was removed from the cells by the glutathione
      synthetase inhibitor L-buthionine-(S,R)-sulfoximine. However, the reducing agent
      dithiothreitol, which prevented the build up of Pr-SSGs in the cell, also blocked
      the accumulation of Ub proteins induced by cadmium. In addition, dithiothreitol
      blocked the effects of the higher toxic (50 microM) concentrations of cadmium on
      cytotoxicity and on glutathione, Pr-SSGs, and Ub proteins. Together, these
      results strongly suggest that changes in the levels of intracellular Pr-SSGs and
      ubiquitin-protein conjugates in neuronal cells are responses closely associated
      with the disruption of intracellular sulfhydryl homeostasis caused by cadmium
      mediated oxidative stress.

PMID- 9582294
TI  - Phosphatidic acid-induced elevation of intracellular Ca2+ is mediated by RhoA and
      H2O2 in Rat-2 fibroblasts.
AB  - We have investigated possible roles of RhoA and H2O2 in the elevation of
      intracellular Ca2+ ([Ca2+]i) by phosphatidic acid (PA) in Rat-2 fibroblasts. PA
      induced a transient elevation of [Ca2+]i in the presence or absence of EGTA.
      Lysophosphatidic acid (LPA) also increased [Ca2+]i, but the sustained Ca2+
      response was inhibited by EGTA. LPA stimulated the production of inositol
      phosphates, but PA did not. In the presence of EGTA, preincubation with LPA
      completely blocked the subsequent elevation of [Ca2+]i by PA, but not vice versa.
      PA stimulated the translocation of RhoA to the particulate fraction as did LPA.
      Scrape loading of C3 transferase inhibited the transient Ca2+ response to PA, but
      not to LPA, suggesting an essential role of RhoA in the elevation of [Ca2+]i by
      PA. H2O2 also induced a transient increase of [Ca2+]i as did PA. H2O2 scavengers,
      catalase and N-acetyl-L-cysteine, completely blocked the rise of [Ca2+]i
      stimulated by PA, but not by LPA. Furthermore, preincubation with PA blocked the
      subsequent Ca2+ response to H2O2, and the incubation with H2O2 also blocked the
      PA-induced rise of [Ca2+]i. Thus, it was suggested that PA stimulated Ca2+
      release from PA-sensitive, but not inositol 1,4,5-trisphosphate-sensitive, Ca2+
      stores by the activation of RhoA and intracellular H2O2.

PMID- 9582295
TI  - Hydrogen peroxide formation by reaction of peroxynitrite with HEPES and related
      tertiary amines. Implications for a general mechanism.
AB  - Organic amine-based buffer compounds such as HEPES (Good's buffers) are commonly
      applied in experimental systems, including those where the biological effects of
      peroxynitrite are studied. In such studies 3-morpholinosydnonimine N
      ethylcarbamide (SIN-1), a compound that simultaneously releases nitric oxide
      (.NO) and superoxide (O-2), is often used as a source for peroxynitrite. Whereas
      in mere phosphate buffer H2O2 formation from 1.5 mM SIN-1 was low ( approximately
      15 microM), incubation of SIN-1 with Good's buffer compounds resulted in
      continuous H2O2 formation. After 2 h of incubation of 1.5 mM SIN-1 with 20 mM
      HEPES about 190 microM H2O2 were formed. The same amount of H2O2 could be
      achieved from 1.5 mM SIN-1 by action of superoxide dismutase in the absence of
      HEPES. The increased H2O2 level, however, could not be related to a superoxide
      dismutase or to a NO scavenger activity of HEPES. On the other hand, SIN-1
      mediated oxidation of both dihydrorhodamine 123 and deoxyribose as well as
      peroxynitrite-dependent nitration of p-hydroxyphenylacetic acid were strongly
      inhibited by 20 mM HEPES. Furthermore, the peroxynitrite scavenger tryptophan
      significantly reduced H2O2 formation from SIN-1-HEPES interactions. These
      observations suggest that peroxynitrite is the initiator for the enhanced
      formation of H2O2. Likewise, authentic peroxynitrite (1 mM) also induced the
      formation of both O-2 and H2O2 upon addition to HEPES (400 mM)-containing
      solutions in a pH (4.5-7.5)-dependent manner. In accordance with previous reports
      it was found that at pH >/=5 oxygen is released in the decay of peroxynitrite. As
      a consequence, peroxynitrite(1 mM)-induced H2O2 formation ( approximately 80
      microM at pH 7.5) also occurred under hypoxic conditions. In the presence of
      bicarbonate/carbon dioxide (20 mM/5%) the production of H2O2 from the reaction of
      HEPES with peroxynitrite was even further stimulated. Addition of SIN-1 or
      authentic peroxynitrite to solutions of Good's buffers resulted in the formation
      of piperazine-derived radical cations as detected by ESR spectroscopy. These
      findings suggest a mechanism for H2O2 formation in which peroxynitrite (or any
      strong oxidant derived from it) initially oxidizes the tertiary amine buffer
      compounds in a one-electron step. Subsequent deprotonation and reaction of the
      intermediate alpha-amino alkyl radicals with molecular oxygen leads to the
      formation of O-2, from which H2O2 is produced by dismutation. Hence, HEPES and
      similar organic buffers should be avoided in studies of oxidative compounds.
      Furthermore, this mechanism of H2O2 formation must be regarded to be a rather
      general one for biological systems where sufficiently strong oxidants may
      interact with various biologically relevant amino-type molecules, such as ATP,
      creatine, or nucleic acids.

PMID- 9582296
TI  - Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac
      myocytes.
AB  - The gap junction protein connexin-43 is normally located at the intercalated
      discs of cardiac myocytes, and it plays a critical role in the synchronization of
      their contraction. The mechanism by which connexin-43 is localized within cardiac
      myocytes is unknown. However, localization of connexin-43 likely involves an
      interaction with the cytoskeleton; immunofluorescence microscopy showed that in
      cardiac myocytes, connexin-43 specifically colocalizes with the cytoskeletal
      proteins ZO-1 and alpha-spectrin. In transfected HEK293 cells,
      immunoprecipitation experiments using coexpressed epitope-tagged connexin-43 and
      ZO-1 indicated that ZO-1 links connexin-43 with alpha-spectrin. The domains
      responsible for the protein-protein interaction between connexin-43 and ZO-1 were
      identified using affinity binding assays with deleted ZO-1 and connexin-43 fusion
      proteins. Immunoblot analysis of associated proteins showed that the C-terminal
      domain of connexin-43 binds to the N-terminal domain of ZO-1. The role of this
      linkage in gap junction formation was examined by a dominant-negative assay using
      the N-terminal domain of ZO-1. Overexpression of the N-terminal domain of ZO-1 in
      connexin-43-expressing cells resulted in redistribution of connexin-43 from cell
      cell interfaces to cytoplasmic structures; this intracellular redistribution of
      connexin-43 coincided with a loss of electrical coupling. We therefore conclude
      that the linkage between connexin-43 and alpha-spectrin, via ZO-1, may serve to
      localize connexin-43 at the intercalated discs, thereby generating functional gap
      junctions in cardiac myocytes.

PMID- 9582297
TI  - Mapping drug interactions at the covalent topoisomerase II-DNA complex by
      bisantrene/amsacrine congeners.
AB  - To identify structural determinants for the sequence-specific recognition of
      covalent topoisomerase II-DNA complexes by anti-cancer drugs, we investigated a
      number of bisantrene congeners, including a 10-azabioisoster, bearing one or two
      4, 5-dihydro-1H-imidazol-2-yl hydrazone side chains at positions 1, 4, or 9 of
      the anthracene ring system. The studied bisantrene/amsacrine (m-AMSA) hybrid and
      bisantrene isomers were able to poison DNA topoisomerase II with an intermediate
      activity between those of bisantrene and m-AMSA. Moving the side chain from the
      central to a lateral ring (from C-9 to C-1/C-4) only slightly modified the drug
      DNA affinity, whereas it dramatically affected local base preferences of poison
      stimulated DNA cleavage. In contrast, switching the planar aromatic systems of
      bisantrene and m-AMSA did not substantially alter the sequence specificity of
      drug action. A computer-assisted steric and electrostatic alignment analysis of
      the test compounds was in agreement with the experimental data, since a common
      pharmacophore was shared by bisantrene, m-AMSA, and 9-substituted analogs,
      whereas the 1-substituted isomer showed a radically changed pharmacophoric
      structure. Thus, the relative space occupancy and electron distribution of
      putative DNA binding (aromatic rings) and enzyme binding (side chains) moieties
      are fundamental in directing the specific action of topoisomerase II poisons and
      in determining the poison pharmacophore.

PMID- 9582298
TI  - A short peptide motif at the carboxyl terminus is required for incorporation of
      the integral membrane MAL protein to glycolipid-enriched membranes.
AB  - The MAL (VIP17, MVP17) proteolipid, an integral membrane protein with specific
      residence in glycolipid-enriched membrane (GEM) microdomains, has been recently
      proposed as a component of the protein machinery for GEM vesiculation. In this
      work, we have searched the COOH terminus of MAL for sorting determinants
      responsible for targeting to GEMs. This has allowed the identification of the
      sequence Leu-Ile-Arg-Trp (LIRW) as necessary for the access of MAL to GEMs. This
      motif requires at least one additional amino acid at its COOH end for full
      effectiveness. The arginine within the LIRW motif is the most crucial residue for
      targeting to GEMs, tryptophan replacement affects targeting to a lesser extent,
      and the leucine-isoleucine pair tolerates substitution by valine, but not by
      alanine, without effect on targeting. Pulse-chase experiments indicate that the
      LIRW tetrapeptide is required for access to GEMs early after MAL biosynthesis.
      Interestingly, the loss of the capacity of the MAL protein to be incorporated
      into GEMs correlated with the loss of its response to brefeldin A treatment. This
      is the first identification of a juxtamembrane peptide motif required for
      incorporation of an integral membrane protein into GEMs.

PMID- 9582299
TI  - Signaling pathways involved in thrombin-induced cell protection.
AB  - This study examined the signal transduction pathways involved in thrombin-induced
      neuroprotection and compares these results with those of a similar study of
      thrombin-induced neuronal death. In thrombin-induced protection of astrocytes
      from hypoglycemia, pretreatment of astrocytes with tyrosine or serine/threonine
      kinase inhibitors, cytochalasin D, or exoenzyme C3, a potent inhibitor of the
      small GTPase RhoA, attenuated thrombin-induced protection. These same inhibitors
      were previously shown to block thrombin-induced cell death, implying a similarity
      in the cell death and cell-protective pathways. Biochemical assays determined
      that thrombin increased available RhoA activity, although more slowly and to a
      lesser extent than occurs in thrombin-induced cell death. A clear difference in
      these pathways was revealed when a time course study of thrombin-induced cell
      death indicated that unlike thrombin-induced protection, cells must be exposed to
      thrombin for >16 h to irreversibly enter the cell death pathway. Addition of
      lower doses of thrombin every 24 h also induced cell death. These studies
      indicate that exposure of cells to micromolar concentrations of thrombin alone
      does not induce cell death, but the continued exposure to thrombin is required.
      Thus the cell death and protective pathways may share initial signaling proteins,
      but differences in the amplitude as well as the duration of the signal may result
      in different final pathways.

PMID- 9582300
TI  - Energy thresholds in brain mitochondria. Potential involvement in
      neurodegeneration.
AB  - Decreases in mitochondrial respiratory chain complex activities have been
      implicated in neurodegenerative disorders such as Parkinson's disease,
      Huntington's disease, and Alzheimer's disease. However, the extent to which these
      decreases cause a disturbance in oxidative phosphorylation and energy homeostasis
      in the brain is not known. We therefore examined the relative contribution of
      individual mitochondrial respiratory chain complexes to the control of NAD-linked
      substrate oxidative phosphorylation in synaptic mitochondria. Titration of
      complex I, III, and IV activities with specific inhibitors generated threshold
      curves that showed the extent to which a complex activity could be inhibited
      before causing impairment of mitochondrial energy metabolism. Complex I, III, and
      IV activities were decreased by approximately 25, 80, and 70%, respectively,
      before major changes in rates of oxygen consumption and ATP synthesis were
      observed. These results suggest that, in mitochondria of synaptic origin, complex
      I activity has a major control of oxidative phosphorylation, such that when a
      threshold of 25% inhibition is exceeded, energy metabolism is severely impaired,
      resulting in a reduced synthesis of ATP. Additionally, depletion of glutathione,
      which has been reported to be a primary event in idiopathic Parkinson's disease,
      eliminated the complex I threshold in PC12 cells, suggesting that antioxidant
      status is important in maintaining energy thresholds in mitochondria. The
      implications of these findings are discussed with respect to neurodegenerative
      disorders and energy metabolism in the synapse.

PMID- 9582301
TI  - Distinctions in agonist and antagonist specificity conferred by anionic residues
      of the nicotinic acetylcholine receptor.
AB  - Two anionic residues in the nicotinic acetylcholine receptor, Asp-152 in the
      alpha-subunit and Asp-174 in the gamma-subunit or the corresponding Asp-180 in
      the delta-subunit, are presumed to reside near the two agonist binding sites at
      the alphagamma and alphadelta subunit interfaces of the receptor and have been
      implicated in electrostatic attraction of cationic ligands. Through site-directed
      mutagenesis and analysis of state changes in the receptor elicited by agonists,
      we have distinguished the roles of anionic residues in conferring ligand
      specificity and ligand-induced state changes. alphaAsp-152 affects agonist and
      antagonist affinity similarly, whereas gammaAsp-174 and deltaAsp-180 primarily
      affect agonist affinity. Combining charge neutralization on the alpha subunit
      with that on the gamma and delta subunits shows an additivity in free energy
      changes for carbamylcholine and d-tubocurarine, suggesting independent
      contributions of these residues to stabilizing the bound ligands. Since both
      aromatic and anionic residues stabilize cationic ligands, we substituted
      tyrosines (Y) for the aspartyl residues. While the substitution, alphaD152Y,
      reduced the affinities for agonists and antagonists, the gammaD174Y/deltaD180Y
      mutations reduced the affinity for agonist binding, but surprisingly enhanced the
      affinity for d-tubocurarine. To ascertain whether selective changes in agonist
      binding stem from the capacity of agonists to form the desensitized state of the
      receptor, carbamylcholine binding was measured in the presence of an allosteric
      inhibitor, proadifen. Mutant nAChRs carrying alphaD152Q or gammaD174N/deltaD180N
      show similar reductions in dissociation constants for the desensitized compared
      with activable receptor state and a similar proadifen concentration dependence.
      Hence, these mutations influence ligand recognition rather than the capacity of
      the receptor to desensitize. By contrast, the alphaD200Q mutation diminishes the
      ratio of dissociation constants for two states and requires higher proadifen
      concentrations to induce desensitization. Thus, the contributions of alphaAsp
      152, gamma/deltaAsp-174/180, and alphaAsp-200 in stabilizing ligand binding can
      be distinguished by the interactions between agonists and allosteric inhibitors.

PMID- 9582302
TI  - The thiol-specific antioxidant enzyme prevents mitochondrial permeability
      transition. Evidence for the participation of reactive oxygen species in this
      mechanism.
AB  - Mitochondrial swelling and membrane protein thiol oxidation associated with
      mitochondrial permeability transition induced by Ca2+ and inorganic phosphate are
      inhibited in a dose-dependent manner either by catalase, the thiol-specific
      antioxidant enzyme (TSA), a protein recently demonstrated to present thiol
      peroxidase activity, or ebselen, a selenium-containing heterocycle which also
      possesses thiol peroxidase activity. This inhibition of mitochondrial
      permeability transition is due to the removal of mitochondrial-generated H2O2
      which can easily diffuse to the extramitochondrial space. Whereas ebselen
      required the presence of reduced glutathione as a reductant to grant its
      protective effect, TSA was fully reduced by mitochondrial components. Decrease in
      the oxygen concentration of the reaction medium also inhibits mitochondrial
      permeabilization and membrane protein thiol oxidation, in a concentration
      dependent manner. The results presented in this report confirm that mitochondrial
      permeability transition induced by Ca2+ and inorganic phosphate is reactive
      oxygen species-dependent. The possible importance of TSA as an intracellular
      antioxidant, avoiding the onset of mitochondrial permeability transition, is
      discussed in the text.

PMID- 9582303
TI  - A family of human beta3-galactosyltransferases. Characterization of four members
      of a UDP-galactose:beta-N-acetyl-glucosamine/beta-nacetyl-galactosamine beta-1,3
      galactosyltransferase family.
AB  - BLAST analysis of expressed sequence tags (ESTs) using the coding sequence of a
      human UDP-galactose:beta-N-acetyl-glucosamine beta-1, 3-galactosyltransferase,
      designated beta3Gal-T1, revealed no ESTs with identical sequences but a large
      number with similarity. Three different sets of overlapping ESTs with sequence
      similarities to beta3Gal-T1 were compiled, and complete coding regions of these
      genes were obtained. Expression of two of these genes in the Baculo virus system
      showed that one represented a UDP-galactose:beta-N-acetyl-glucosamine beta-1, 3
      galactosyltransferase (beta3Gal-T2) with similar kinetic properties as beta3Gal
      T1. Another gene represented a UDP-galactose:beta-N-acetyl-galactosamine beta-1,
      3-galactosyltransferase (beta3Gal-T4) involved in GM1/GD1 ganglioside synthesis,
      and this gene was highly similar to a recently reported rat GD1 synthase
      (Miyazaki, H., Fukumoto, S., Okada, M., Hasegawa, T., and Furukawa, K. (1997) J.
      Biol. Chem. 272, 24794-24799). Northern analysis of mRNA from human organs with
      the four homologous cDNA revealed different expression patterns. beta3Gal-T1 mRNA
      was expressed in brain, beta3Gal-T2 was expressed in brain and heart, and
      beta3Gal-T3 and -T4 were more widely expressed. The coding regions for each of
      the four genes were contained in single exons. beta3Gal-T2, -T3, and -T4 were
      localized to 1q31, 3q25, and 6p21.3, respectively, by EST mapping. The results
      demonstrate the existence of a family of homologous beta3-galactosyltransferase
      genes.

PMID- 9582304
TI  - Multiple signalling pathways lead to the activation of the nuclear factor kappaB
      by the Rho family of GTPases.
AB  - Members of the Rho family of small GTPases activate the nuclear factor kappaB (NF
      kappaB) (Perona, R., Montaner, S., Saniger, L., Sanchez-Perez, I., Bravo, R., and
      Lacal, J. C. (1997), Genes & Dev. 11, 463-475). We have investigated whether
      different members of the family of exchange factors specific for Rho proteins
      (Dbl family) could activate the transcription factor NF-kappaB and have explored
      both their specificity under in vivo conditions and the mechanisms involved.
      Activated forms of Dbl, Ost, and Vav proteins induce NF-kappaB activation. While
      the activation induced by the Vav oncogen was efficiently inhibited by a dominant
      negative mutant of Rac1, the corresponding mutant of Cdc42Hs was able to block
      selectively NF-kappaB activation mediated by Dbl. Finally, mutants of RhoA and
      Cdc42Hs, but not that of Rac1, inhibited the activation of NF-kappaB by Ost.
      Thus, under in vivo conditions, different members of the Dbl family are related
      to specific Rho GTPases for the regulation of NF-kappaB. Activation of NF-kappaB
      by Rho or Ras proteins is mutually independent. However, there is a link between
      the NF-kappaB and the c-Jun N-terminal kinase/stress-activated protein kinase
      (JNK/SAPK) cascades since a dominant negative mutant of MEKK1 is able to inhibit
      NF-kappaB activation induced by Rac1 and Cdc42Hs proteins, but not by RhoA. These
      results indicate that, in mammalian cells, multiple pathways coexist for the
      activation of NF-kappaB, some of which are mediated by specific members of the
      Ras and Rho families of small GTPases.

PMID- 9582305
TI  - Nonmyogenic factors bind nicotinic acetylcholine receptor promoter elements
      required for response to denervation.
AB  - Nicotinic acetylcholine receptors (AChRs) belong to a class of muscle proteins
      whose expression is regulated by muscle electrical activity. In innervated muscle
      fiber, AChR genes are transcriptionally repressed outside of the synapse, while
      after denervation they become reexpressed throughout the fiber. The myogenic
      determination factors (MDFs) of the MyoD family have been shown to play a central
      role in this innervation-dependent regulation. In the chicken AChR alpha-subunit
      gene promoter, two E-boxes that bind MDFs are necessary to achieve the
      enhancement of transcription following muscle denervation. However, the deletion
      of promoter sequences located upstream to these E-boxes greatly impairs the
      response to denervation (Bessereau, J. L., Stratford- Perricaudet, L. D., Piette,
      J., Le Poupon, C. and Changeux, J. P. (1994) Proc. Natl. Acad. Sci. U. S. A. 91,
      1304-1308). Here we identified two additional cis-regulatory elements of the
      alpha-subunit gene promoter that cooperate with the E-boxes in the denervation
      response. One region binds the Sp1 and Sp3 zinc finger transcription factors. The
      second region binds at least three distinct factors, among which we identified an
      upstream stimulatory factor, a b-ZIP-HLH transcription factor. We propose that
      among MDF-responsive muscle promoters, a specific combination between myogenic
      and nonmyogenic factors specify innervation-dependent versus innervation
      independent promoters.

PMID- 9582306
TI  - A point mutation in Galphao and Galphai1 blocks interaction with regulator of G
      protein signaling proteins.
AB  - Regulator of G protein-signaling (RGS) proteins accelerate GTP hydrolysis by
      Galpha subunits and are thought to be responsible for rapid deactivation of
      enzymes and ion channels controlled by G proteins. We wanted to identify and
      characterize Gi-family alpha subunits that were insensitive to RGS action. Based
      on a glycine to serine mutation in the yeast Galpha subunit Gpa1(sst) that
      prevents deactivation by Sst2 (DiBello, P. R., Garrison, T. R., Apanovitch, D.
      M., Hoffman, G., Shuey, D. J., Mason, K., Cockett, M. I., and Dohlman, H. G.
      (1998) J. Biol. Chem. 273, 5780-5784), site-directed mutagenesis of alphao and
      alphai1 was done. G184S alphao and G183S alphai1 show kinetics of GDP release and
      GTP hydrolysis similar to wild type. In contrast, GTP hydrolysis by the G --> S
      mutant proteins is not stimulated by RGS4 or by a truncated RGS7. Quantitative
      flow cytometry binding studies show IC50 values of 30 and 96 nM, respectively,
      for aluminum fluoride-activated wild type alphao and alphai1 to compete with
      fluorescein isothiocyanate-alphao binding to glutathione S-transferase-RGS4. The
      G --> S mutant proteins showed a greater than 30-100-fold lower affinity for
      RGS4. Thus, we have defined the mechanism of a point mutation in alphao and
      alphai1 that prevents RGS binding and GTPase activating activity. These mutant
      subunits should be useful in biochemical or expression studies to evaluate the
      role of endogenous RGS proteins in Gi function.

PMID- 9582307
TI  - Identification of a transforming growth factor-beta1/bone morphogenetic protein 4
      (TGF-beta1/BMP4) response element within the mouse tissue transglutaminase gene
      promoter.
AB  - Tissue transglutaminase is a calcium-dependent, protein cross-linking enzyme that
      is highly expressed in cells undergoing apoptosis. The expression of tissue
      transglutaminase is regulated by a variety of molecules including retinoids,
      interleukin-6, and transforming growth factor-beta1 (TGF-beta1). Retinoid and
      interleukin-6 inductions of tissue transglutaminase expression are mediated by
      specific cis-regulatory elements located within the first 4.0 kilobase pairs of
      the promoter of the gene. The present studies were designed to identify the
      molecular mechanisms mediating the regulation of tissue transglutaminase gene
      expression by TGF-beta family members. Transient transfection of Mv1Lu cells with
      transglutaminase promoter constructs demonstrated that 0.2 nM TGF-beta1 maximally
      induced the activation of the promoter through a 10-base pair TGF-beta1 response
      element (TRE; GAGTTGGTGC) located 868 base pairs upstream of the transcription
      start site. This same element mediated an inhibitory activity of TGF-beta1 on the
      transglutaminase promoter in MC3T3 E1 cells. The TRE through which TGF-beta1
      regulated the activity of the transglutaminase promoter was necessary and
      sufficient for bone morphogenetic protein 2- (BMP) and BMP4-dependent inhibition
      of the tissue transglutaminase promoter. The TGF-beta1, BMP2, and BMP4 regulation
      of the transglutaminase promoter activity was similar to the responses we
      observed for the endogenous transglutaminase activity of Mv1Lu and MC3T3 E1
      cells. For BMP2 and BMP4, this regulation was paralleled by a decrease in tissue
      transglutaminase mRNA in MC3T3 E1 cells. The results of these experiments suggest
      that TGF-beta1, BMP2, and BMP4 regulation of mouse tissue transglutaminase gene
      expression requires a composite TRE located in the 5'-flanking DNA.

PMID- 9582308
TI  - Characterization of the region involved in CD3 pairwise interactions within the T
      cell receptor complex.
AB  - Assembly of the six-chain T cell antigen receptor-CD3 complex takes place by
      pairwise interactions. Thus, CD3-epsilon interacts with either CD3-gamma or CD3
      delta, and these dimers then associate with the TCR heterodimer (alpha.beta or
      gamma.delta) and the CD3-zeta homodimer to constitute a full complex. We have now
      mapped the site in CD3-epsilon responsible for the interaction with CD3-gamma and
      CD3-delta by analysis of a series of deletional mutants encompassing the most
      conserved regions. We found that the highly conserved juxtamembrane domain is
      mainly responsible for the interaction. Thus, deletion of this 16-amino acid
      extracellular sequence resulted in the inhibition of up to 95% of the CD3
      epsilon/gamma interaction. A highly conserved sequence is also present in both
      CD3-gamma and CD3-delta, suggesting that the domain in these two chains may
      reciprocally be involved in the interaction with CD3-epsilon. Indeed, an
      immobilized synthetic peptide corresponding to the CD3-gamma sequence
      specifically associated to a bacterially expressed CD3-epsilon protein,
      suggesting the 16-amino acid domain is sufficient to promote CD3-epsilon/CD3
      gamma assembly. The conservation of the motif in the CD3 chains suggest that, in
      addition to CD3-epsilon/CD3-gamma and CD3-epsilon/CD3-delta interactions, it may
      also mediate homotypic interactions. Indeed, it is shown that it mediates the
      formation of disulfide-linked homodimers and that the formation of homo- and
      heterodimers are mutually excluded. Finally, this domain contains a Cys-X-X-Cys
      sequence that resembles that of p56(lck), which is responsible for the
      interaction with the cytoplasmic tails of CD4 and CD8. Since the replacement of
      the two cysteines (Cys97 and Cys100) in CD3-epsilon by alanines strongly
      inhibited pair formation, the existence of a Cys-X-X-Cys motif involved in
      protein-protein interactions is suggested.

PMID- 9582309
TI  - Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions
      representing physiological acidosis.
AB  - The cortical deposition of Abeta is an event that occurs in Alzheimer's disease,
      Down's syndrome, head injury, and normal aging. Previously, in appraising the
      effects of different neurochemical factors that impact upon the solubility of
      Abeta, we observed that Zn2+ was the predominant bioessential metal to induce the
      aggregation of soluble Abeta at pH 7.4 in vitro and that this reaction is totally
      reversible with chelation. We now report that unlike other biometals tested at
      maximal biological concentrations, marked Cu2+-induced aggregation of Abeta1-40
      emerged as the solution pH was lowered from 7.4 to 6.8 and that the reaction was
      completely reversible with either chelation or alkalinization. This interaction
      was comparable to the pH-dependent effect of Cu2+ on insulin aggregation but was
      not seen for aprotinin or albumin. Abeta1-40 bound three to four Cu2+ ions when
      precipitated at pH 7.0. Rapid, pH-sensitive aggregation occurred at low nanomolar
      concentrations of both Abeta1-40 and Abeta1-42 with submicromolar concentrations
      of Cu2+. Unlike Abeta1-40, Abeta1-42 was precipitated by submicromolar Cu2+
      concentrations at pH 7.4. Rat Abeta1-40 and histidine-modified human Abeta1-40
      were not aggregated by Zn2+, Cu2+, or Fe3+, indicating that histidine residues
      are essential for metal-mediated Abeta assembly. These results indicate that H+
      induced conformational changes unmask a metal-binding site on Abeta that mediates
      reversible assembly of the peptide. Since a mildly acidic environment together
      with increased Zn2+ and Cu2+ are common features of inflammation, we propose that
      Abeta aggregation by these factors may be a response to local injury. Cu2+, Zn2+,
      and Fe3+ association with Abeta explains the recently reported enrichment of
      these metal ions in amyloid plaques in Alzheimer's disease.

PMID- 9582310
TI  - Molecular and functional properties of a calpain activator protein specific for
      mu-isoforms.
AB  - A natural calpain activator protein has been isolated from bovine brain and
      characterized in its properties and molecular structure. The protein is a
      homodimer with a molecular mass of about 30 kDa and results in being almost
      identical to UK114 goat liver protein. Significant similarities with mouse HR12
      protein were also observed, whereas a lower degree of similarity was found with a
      family of heat-responsive proteins named YJGF and YABJ from Haemophilus
      influenzae and Bacillus subtilis, respectively. The brain activator expresses a
      strict specificity for the mu-calpain isoform, being completely ineffective on
      the m-calpain form. As expected, also UK114 was found to possess calpain
      activating properties, indistinguishable from those of bovine brain activator. A
      protein showing the same calpain-activating activity has been also isolated from
      human red cells, indicating that this factor is widely expressed. All these
      activators are efficient on mu-calpain independently from the source of the
      proteinase. The high degree of specificity of the calpain activator for a single
      calpain isoform may be relevant for the understanding of sophisticated
      intracellular mechanisms underlying intracellular proteolysis. These data are
      indicating the existence of a new component of the Ca2+-dependent proteolytic
      system, constituted of members of a chaperonin-like protein family and capable of
      promoting intracellular calpain activation.

PMID- 9582311
TI  - Effects of poliovirus 3AB protein on 3D polymerase-catalyzed reaction.
AB  - Poliovirus RNA replication requires the activities of a viral RNA-dependent RNA
      polymerase, 3Dpol, in conjunction with several additional viral and likely
      cellular proteins. The importance of both the 3A and 3B coding regions has been
      documented previously by genetic tests, and their biochemical activities have
      been the subject of several recent investigations. In this study, we examined the
      previously reported stimulation of 3D-catalyzed RNA synthesis by 3AB. We show
      that 3AB does not stimulate RNA synthesis on templates that are stably base
      paired to a primer, indicating that 3AB does not stabilize or otherwise activate
      3Dpol for chain elongation. Similarly, it does not alter the kinetic parameters
      or binding affinities of 3D for substrates. In the absence of a primer, or in the
      presence of a primer that does not form a stable hybrid with the template, 3AB
      increases the utilization of 3'-hydroxyl termini as sites for chain elongation by
      3D, and thereby stimulates RNA synthesis. 3AB may interact with and stabilize
      these sites and/or may recruit 3Dpol to the site, resulting in stimulation of the
      initiation of elongation events. We propose that this activity is required for
      stabilizing weak interactions that occur during nucleotidyl-protein-primed
      initiation events in the viral RNA replication complex.

PMID- 9582312
TI  - Regulation of guanine nucleotide exchange through phosphorylation of eukaryotic
      initiation factor eIF2alpha. Role of the alpha- and delta-subunits of eiF2b.
AB  - The guanine nucleotide exchange activity of eIF2B plays a key regulatory role in
      the translation initiation phase of protein synthesis. The activity is markedly
      inhibited when the substrate, i. e. eIF2, is phosphorylated on Ser51 of its alpha
      subunit. Genetic studies in yeast implicate the alpha-, beta-, and delta-subunits
      of eIF2B in mediating the inhibition by substrate phosphorylation. However, the
      mechanism involved in the inhibition has not been defined biochemically. In the
      present study, we have coexpressed the five subunits of rat eIF2B in Sf9 cells
      using the baculovirus system and have purified the recombinant holoprotein to
      >90% homogeneity. We have also expressed and purified a four-subunit eIF2B
      complex lacking the alpha-subunit. Both the five- and four-subunit forms of eIF2B
      exhibit similar rates of guanine nucleotide exchange activity using
      unphosphorylated eIF2 as substrate. The five-subunit form is inhibited by
      preincubation with phosphorylated eIF2 (eIF2(alphaP)) and exhibits little
      exchange activity when eIF2(alphaP) is used as substrate. In contrast, eIF2B
      lacking the alpha-subunit is insensitive to inhibition by eIF2(alphaP) and is
      able to exchange guanine nucleotide using eIF2(alphaP) as substrate at a faster
      rate compared with five-subunit eIF2B. Finally, a double point mutation in the
      delta-subunit of eIF2B has been identified that results in insensitivity to
      inhibition by eIF2(alphaP) and exhibits little exchange activity when
      eIF2(alphaP) is used as substrate. The results provide the first direct
      biochemical evidence that the alpha- and delta-subunits of eIF2B are involved in
      mediating the effect of substrate phosphorylation.

PMID- 9582313
TI  - Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP
      ribosylation factor regulates hPLD2.
AB  - Phospholipase D (PLD) has been implicated in a variety of cellular processes
      including vesicular transport, the respiratory burst, and mitogenesis. PLD1,
      first cloned from human, is activated by small GTPases such as ADP-ribosylation
      factor (ARF) and RhoA. Rodent PLD2, which is approximately 50% identical to PLD1
      has recently been cloned from mouse embryo (Colley, W., Sung, T., Roll, R.,
      Jenco, J., Hammond, S., Altshuller, Y., Bar-Sagi, D., Morris, A., and Frohman, M.
      (1997) Curr. Biol. 7, 191-201) and rat brain (Kodaki, T., and Yamashita, S.
      (1997) J. Biol. Chem. 272, 11408-11413). We describe herein the cloning from a B
      cell library and expression of human PLD2 (hPLD2). The open reading frame is
      predicted to encode a 933-amino acid protein (Mr of 105,995); this corresponds to
      the size of the protein expressed in insect cells using recombinant baculovirus.
      The deduced amino acid sequence shows 53 and 90% identity to hPLD1 and rodent
      PLD2, respectively. The mRNA for PLD2 was widely distributed in various tissues
      including peripheral blood leukocytes, and the distribution was distinctly
      different from that of hPLD1. hPLD1 and hPLD2 both showed a requirement for
      phosphatidylinositol 4,5-bisphosphate. Both isoforms showed optimal activity at
      10-20 mol % phosphatidylcholine in a mixed lipid vesicle system and showed
      comparable basal activities in the presence of phosphatidylinositol 4,5
      bisphosphate. Unexpectedly, ARF-1 stimulated the activity of hPLD2 expressed in
      insect cells about 2-fold, compared with a 20-fold stimulation of hPLD1 activity.
      Thus, not only PLD1 but also hPLD2 activity can be positively regulated by both
      phosphatidylinositol 4,5-bisphosphate and ARF.

PMID- 9582314
TI  - Identification of amino acid residues contributing to desensitization of the P2X2
      receptor channel.
AB  - The P2X2 receptor (P2X2R) is a member of the ATP-gated ion channels that mediate
      Ca2+ entry in several tissues, including the brain, adrenal medulla, and
      pituitary. Alternative usage of cryptic splice sites in the primary P2X2R
      transcript accounts for the existence of several transcript types, one of which
      (P2X2-2R) encodes a functional channel. P2X2-2R lacks a stretch of cytoplasmic C
      terminal amino acids (Val370-Gln438) and exhibits rapid and complete
      desensitization, whereas P2X2R desensitizes slowly and incompletely. The role of
      the C terminus in P2X2R desensitization was studied by generating several channel
      mutants and monitoring intracellular free Ca2+ changes in transfected single GT1
      7 neurons. Deletion studies indicated that the Arg371-Ile391 segment of the P2X2R
      is required for sustained Ca2+ influx. To identify the important residues within
      this segment, three contiguous amino acids were sequentially changed to alanine.
      Only two of these replacement mutants, at Arg371-Thr372-Pro373 and Lys374-His375
      Pro376, had an enhanced rate of desensitization. Single amino acid deletions in
      the P2X2R C terminus and a series of insertions of wild-type sequences into the
      corresponding spliced site identified four residues, Pro373-Lys374-His375-Pro376,
      required for sustained Ca2+ influx through agonist-occupied wild-type channels.
      Thus, it is likely that the Pro373-Pro376 sequence of P2X2R represents a
      functional motif that is critical for the development of the slow desensitization
      profile observed in these channels. Consequently, deletion of this motif by
      alternative splicing provides an effective mechanism for generating a channel
      with controlled Ca2+ influx.

PMID- 9582315
TI  - Endoplasmic reticulum stress proteins block oxidant-induced Ca2+ increases and
      cell death.
AB  - Oxidants are important human toxicants. Increased intracellular free Ca2+ may be
      critical for oxidant toxicity, but this mechanism remains controversial.
      Furthermore, oxidants damage the endoplasmic reticulum (ER) and release ER Ca2+,
      but the role of the ER in oxidant toxicity and Ca2+ regulation during toxicity is
      also unclear. tert-Butylhydroperoxide (TBHP), a prototypical organic oxidant,
      causes oxidative stress and an increase in intracellular free Ca2+. Therefore, we
      addressed the mechanism of oxidant-induced cell death and investigated the role
      of ER stress proteins in Ca2+ regulation and cytoprotection after treating renal
      epithelial cells with TBHP. Prior ER stress induces expression of the ER stress
      proteins Grp78, Grp94, and calreticulin and rendered cells resistant to cell
      death caused by a subsequent TBHP challenge. Expressing antisense RNA targeted to
      grp78 prevents grp78 induction sensitized cells to TBHP and disrupted their
      ability to develop cellular tolerance. In addition, overexpressing calreticulin,
      another ER chaperone and Ca2+-binding protein, also protected cells against TBHP.
      Interestingly, neither prior ER stress nor calreticulin expression prevented
      lipid peroxidation, but both blocked the rise in intracellular free Ca2+ after
      TBHP treatment. Loading cells with EGTA, even after peroxidation had already
      occurred, also prevented TBHP-induced cell death, indicating that buffering
      intracellular Ca2+ prevents cell killing. Thus, Ca2+ plays an important role in
      TBHP-induced cell death in these cells, and the ER is an important regulator of
      cellular Ca2+ homeostasis during oxidative stress. Given the importance of
      oxidants in human disease, it would appear that the role of ER stress proteins in
      protection from oxidant damage warrants further consideration.

PMID- 9582316
TI  - Characterization of cytochrome c free radical reactions with peptides by mass
      spectrometry.
AB  - The reactions of horse heart cytochrome c, hydrogen peroxide, and the spin trap
      3,5-dibromo-4-nitrosobenzenesulfonic acid with a series of polypeptides were
      investigated using mass spectrometry. The mass spectra obtained from these
      reactions revealed that after a free radical has been generated on the heme
      containing protein horse heart cytochrome c, it can be transferred to other
      biomolecules. In addition, the number of free radicals transferred to the target
      molecule could be determined. Recipient peptides/proteins that contained a
      tyrosine and/or tryptophan amino acid residue were most susceptible to free
      radical transfer. Using tandem mass spectrometry, the location of the 3,5-dibromo
      4-nitrosobenzenesulfonic acid radical adduct on the nonapeptide RWIILGLNK was
      unequivocally determined to be at the tryptophan residue. We also demonstrated
      that the presence of an antioxidant in the reaction mixture not only inhibits
      free radical formation on horse heart cytochrome c, but also interferes with the
      transfer of the free radical, once it has been formed on cytochrome c.

PMID- 9582317
TI  - Conservative mutations in the immunosuppressive region of the bovine leukemia
      virus transmembrane protein affect fusion but not infectivity in vivo.
AB  - Many retroviruses, including bovine leukemia virus (BLV), contain a highly
      conserved region located about 40 amino acids downstream from the fusion peptide
      within the sequence of the external domain of the transmembrane (TM) protein.
      This region is notably thought to be involved in the presentation of the NH2
      terminal peptide to allow cell fusion. By using hydrophobic cluster analysis and
      by analogy with the influenza A hemagglutinin structures, the core of the TM
      structure including this particular region was predicted to consist, in the BLV
      and other retroviral envelope proteins, of an alpha-helix followed by a loop
      region, both docked against a subsequent alpha-helix that forms a triple-stranded
      coiled coil. The loop region could undergo, as in hemagglutinin, a major
      refolding into an alpha-helix integrating the coiled coil structure and putting
      the fusion peptide to one tip of the molecule. Based on this model, we have
      identified amino acids that may be essential to the BLV TM structure, and a
      series of mutations were introduced in the BLV env gene of an infectious
      molecular clone. A first series of mutations was designed to disturb the coiled
      coil structure (substitutions with proline residues), whereas others would
      maintain the general TM structure. When expressed by Semliki Forest virus
      recombinants, all the mutated envelope proteins were stable and efficiently
      synthesized in baby hamster kidney cells. Both proline-substituted and
      conservative mutants were strongly affected in their capacity to fuse to CC81
      indicator cells. In addition, it appeared that the integrity of the TM coiled
      coil structure is essential for envelope protein multimerization, as analyzed by
      metrizamide gradient centrifugation. Finally, to gain insight into the role of
      this coiled coil in the infectious potential of BLV in vivo, the mutated TM genes
      were introduced in an infectious and pathogenic molecular clone and injected into
      sheep. It appeared that only the conservative mutations (A60V and A64S) allowed
      maintenance of viral infectivity in vivo. Since these mutations destroyed the
      ability to induce syncytia, we conclude that efficient fusion capacity of the
      recombinant envelopes is not a prerequisite for the infectious potential of BLV
      in vivo. Viral propagation of these mutants was strongly affected in some of the
      infected sheep. However, the proviral loads within half of the infected animals
      (2 out of 2 for A60V and 1 out of 4 for A64S) were close to the wild-type levels.
      In these sheep, it thus appears that the A60V and A64S mutants propagate
      efficiently despite being unable to induce syncytia in cell culture.

PMID- 9582318
TI  - Primary structure, tissue distribution, and chromosomal localization of a novel
      isoform of lysyl hydroxylase (lysyl hydroxylase 3)
AB  - We report characterization of a novel isoform of lysyl hydroxylase (lysyl
      hydroxylase 3, LH3). The cDNA clones encode a polypeptide of 738 amino acids,
      including a signal peptide. The amino acid sequence has a high overall identity
      with LH1 and LH2, the isoforms characterized earlier. Conserved regions are
      present in the carboxyl-terminal portion of the isoforms and also in the central
      part of the molecules. Histidine and asparagine residues, which are conserved in
      the other isoforms and are known to be required for enzymatic activity, are also
      conserved in the novel isoform. The gene for LH3 (PLOD3) has been assigned to
      human chromosome 7q36 and rat chromosome 12. Gene expression of LH3 is highly
      regulated in adult human tissues. A strong hybridization signal, corresponding to
      an mRNA 2.75 kilobases in size, is obtained in heart, placenta and pancreas on
      multiple tissue RNA blots. Expression of the cDNA in vitro results in the
      synthesis of a protein that hydroxylates lysyl residues in collagenous sequences
      in a non-triple helical conformation.

PMID- 9582319
TI  - Involvement of molecular chaperonins in nucleotide excision repair. Dnak leads to
      increased thermal stability of UvrA, catalytic UvrB loading, enhanced repair, and
      increased UV resistance.
AB  - UvrA is one of the key Escherichia coli proteins involved in removing DNA damage
      during the process of nucleotide excision repair. The relatively low
      concentrations (nanomolar) of the protein in the normal cells raise the potential
      questions about its stability in vivo under both normal and stress conditions. In
      vitro, UvrA at low concentrations is shown to be stabilized to heat inactivation
      by E. coli molecular chaperones DnaK or the combination of DnaK, DnaJ, and GrpE.
      These chaperone proteins allow sub-nanomolar concentrations of UvrA to load UvrB
      through >10 cycles of incision. Guanidine hydrochloride-denatured UvrA was
      reactivated by DnaK, DnaJ, and GrpE to as much as 50% of the native protein
      activity. Co-immunoprecipitation assays showed that DnaK bound denatured UvrA in
      the absence of ATP. UV survival studies of a DnaK-deficient strain indicated an
      80-fold increased sensitivity to 100 J/m2 of ultraviolet light (254 nm) as
      compared with an isogenic wild-type strain. Global repair analysis indicated a
      reduction in the extent of pyrimidine dimer and 6-4 photoproduct removal in the
      DnaK-deficient cells. These results suggest that molecular chaperonins
      participate in nucleotide excision repair by maintaining repair proteins in their
      properly folded state.

PMID- 9582320
TI  - Potential role for ceramide in mitogen-activated protein kinase activation and
      proliferation of vascular smooth muscle cells induced by oxidized low density
      lipoprotein.
AB  - Proliferation of vascular smooth muscle cells (SMC) is a hallmark in the
      pathogenesis of atherosclerotic lesions. Mildly oxidized low density lipoproteins
      (UV-oxLDL), which are mitogenic to cultured AG-08133A SMC, activate the
      sphingomyelin (SM)-ceramide pathway. We report here the following. (i) UV-oxLDL
      elicited a biphasic and sustained activation of MBP kinase activity,
      phosphorylation and nuclear translocation of p44/42 mitogen-activated protein
      kinase (MAPK), and [3H]thymidine incorporation, which were inhibited by PD
      098059, a MAPK kinase inhibitor. (ii) The use of preconditioned media (from SMC
      pre-activated by UV-oxLDL) transferred to native SMC and blocking antibodies
      against growth factors suggest that UV-oxLDL-induced activation of MAPK and
      [3H]thymidine incorporation seem to be independent of any autocrine secretion of
      growth factors. (iii) UV-oxLDL-induced activation of a neutral sphingomyelinase,
      SM hydrolysis, ceramide production, and [3H]thymidine incorporation were
      inhibited by two serine-protease inhibitors (serpins), suggesting that a serpin
      sensitive proteolytic pathway is involved in the activation of the SM-ceramide
      signaling pathway. (iv) UV-oxLDL-induced MAPK activation and [3H]thymidine
      incorporation were mimicked by ceramide generated in the plasma membrane by
      bacterial sphingomyelinase treatment or by addition of the permeant C2-ceramide.
      Serpins did not inhibit the MAPK activation and [3H]thymidine incorporation
      induced by C2-ceramide, indicating that activation of the MAPK and [3H]thymidine
      incorporation is subsequent to the stimulation of the SM-ceramide pathway. Taken
      together, these data suggest that mitogenic concentrations of UV-oxLDL are able
      to stimulate the SM-ceramide pathway through a protease-dependent mechanism and
      activate p44/42 MAPK, leading to proliferation of vascular SMC.

PMID- 9582321
TI  - Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38
      mitogen-activated protein kinase pathway.
AB  - The mitogen-activated protein kinase (MAPK) cascade is believed to function as an
      important regulator of prostaglandin biosynthesis. Previously we reported that
      interleukin-1beta induces activation of JNK/SAPK and p38 MAPK with concomitant up
      regulation of cyclooxygenase (Cox)-2 expression and prostaglandin E2 (PGE2)
      synthesis. Our experiments demonstrate that overexpression of DeltaMEKK1 (a
      constitutively active truncation mutant of MEKK1 containing the C-terminal 324
      amino acids) increases Cox-2 expression and PGE2 production which is completely
      blocked by SC68376, a pharmacologic inhibitor of p38 MAPK. DeltaMEKK1
      overexpression results in activation of both c-Jun N-terminal
      kinases/extracellular signal-regulated kinases (JNK/SAPK) and p38 MAPK.
      Furthermore, activation of MEKK1 increases SEK1/MKK4 but not MKK3 or MKK6
      activity. These findings suggest that MEKK1 --> SEK1/MKK4 may function as an
      upstream kinase capable of activating both p38 MAPK and JNK/SAPK with subsequent
      induction of Cox-2 expression and PGE2 production. We also found that
      overexpression of the constitutively active form of SEK1 (SEK1-ED) increases both
      p38 MAPK and JNK/SAPK phosphorylation, and increases PGE2 production and Cox-2
      expression. By comparison, overexpression of the dominant negative form of SEK1
      (SEK1-AL) decreases the phosphorylation of both p38 MAPK and JNK/SAPK and reduces
      Cox-2 expression. Together, this data suggests a potential role for the MEKK1 -->
      SEK1/MKK4 --> p38 MAPK -->--> Cox-2 cascade linking members of the MAPK pathway
      with prostaglandin biosynthesis.

PMID- 9582322
TI  - Complex interactions of the protein L-isoaspartyl methyltransferase and
      calmodulin revealed with the yeast two-hybrid system.
AB  - The widely distributed protein-L-isoaspartyl, D-aspartyl
      carboxylmethyltransferase (EC 2.1.1.77) is hypothesized to play a role in the
      repair or metabolism of deamidated and isomerized proteins that are spontaneously
      generated during the aging of proteins in cells. The yeast two-hybrid system was
      used to identify proteins that potentially interact with the methyltransferase in
      a cellular processing pathway. Two cDNAs, both encoding calmodulin, were isolated
      from a human fetal brain cDNA library using the human methyltransferase as the
      bait. Enzymatic assays with purified components revealed a complex set of
      interactions between the methyltransferase and calmodulin. Calmodulin weakly
      stimulated protein carboxylmethyltransferase activity in vitro at concentrations
      of the two proteins reflecting their representation in mammalian brain.
      Calmodulin stimulation of methyltransferase was observed in both the presence and
      absence of calcium, although the effect was greater in the presence of calcium.
      Native calmodulin was not a substrate for the carboxylmethyltransferase, but
      deamidated variants of calmodulin act as substrates for the methyltransferase,
      with calculated Km values of 3.6 and 8.6 microM for calcium-liganded and
      unliganded calmodulin, respectively. Both the effector and substrate interactions
      of calmodulin with the protein isoaspartyl methyltransferase likely contributed
      to the positive results obtained with the two-hybrid system.

PMID- 9582323
TI  - Crystal structure of the arcelin-1 dimer from Phaseolus vulgaris at 1.9-A
      resolution.
AB  - Arcelin-1 is a glycoprotein from kidney beans (Phaseolus vulgaris) which displays
      insecticidal properties and protects the seeds from predation by larvae of
      various bruchids. This lectin-like protein is devoid of monosaccharide binding
      properties and belongs to the phytohemagglutinin protein family. The x-ray
      structure determination at 1.9-A resolution of native arcelin-1 dimers, which
      correspond to the functional state of the protein in solution, was solved using
      multiple isomorphous replacement and refined to a crystallographic R factor of
      0.208. The three glycosylation sites on each monomer are all covalently modified.
      One of these oligosaccharide chains provides interactions with protein atoms at
      the dimer interface, and another one may act by preventing the formation of
      higher oligomeric species in the arcelin variants. The dimeric structure and the
      severe alteration of the monosaccharide binding site in arcelin-1 correlate with
      the hemagglutinating properties of the protein, which are unaffected by simple
      sugars and sugar derivatives. Sequence analysis and structure comparisons of
      arcelin-1 with the other insecticidal proteins from kidney beans, arcelin-5, and
      alpha-amylase inhibitor and with legume lectins, yield insights into the
      molecular basis of the different biological functions of these proteins.

PMID- 9582324
TI  - Effect of pp120 on receptor-mediated insulin endocytosis is regulated by the
      juxtamembrane domain of the insulin receptor.
AB  - pp120, a substrate of the insulin receptor tyrosine kinase, does not undergo
      ligand-stimulated phosphorylation by the insulin-like growth factor-1 (IGF-1)
      receptor. However, replacement of the C-terminal domain of the IGF-1 receptor
      beta-subunit with the corresponding segment of the insulin receptor restored
      pp120 phosphorylation by the chimeric receptor. Since pp120 stimulates receptor
      mediated insulin endocytosis when it is phosphorylated, we examined whether pp120
      regulates IGF-1 receptor endocytosis in transfected NIH 3T3 cells. pp120 failed
      to alter IGF-1 receptor endocytosis via either wild-type or chimeric IGF-1
      receptors. Thus, the effect of pp120 on hormone endocytosis is specific to
      insulin, and the C-terminal domain of the beta-subunit of the insulin receptor
      does not regulate the effect of pp120 on insulin endocytosis. Mutation of Tyr960
      in the juxtamembrane domain of the insulin receptor abolished the effect of pp120
      to stimulate receptor endocytosis, without affecting pp120 phosphorylation by the
      insulin receptor. These findings suggest that pp120 interacts with two separate
      domains of the insulin receptor as follows: a C-terminal domain required for
      pp120 phosphorylation and a juxtamembrane domain required for internalization. We
      propose that the interaction of pp120 with the juxtamembrane domain is indirect
      and requires one or more substrates that bind to Tyr960 in the insulin receptor.

PMID- 9582325
TI  - Activation of thiamin diphosphate and FAD in the phosphatedependent pyruvate
      oxidase from Lactobacillus plantarum.
AB  - The phosphate- and oxygen-dependent pyruvate oxidase from Lactobacillus plantarum
      is a homotetrameric enzyme that binds 1 FAD and 1 thiamine diphosphate per
      subunit. A kinetic analysis of the partial reactions in the overall oxidative
      conversion of pyruvate to acetyl phosphate and CO2 shows an indirect activation
      of the thiamine diphosphate by FAD that is mediated by the protein moiety. The
      rate constant of the initial step, the deprotonation of C2-H of thiamine
      diphosphate, increases 10-fold in the binary apoenzyme-thiamine diphosphate
      complex to 10(-2) s-1. Acceleration of this step beyond the observed overall
      catalytic rate constant to 20 s-1 requires enzyme-bound FAD. FAD appears to bind
      in a two-step mechanism. The primarily bound form allows formation of
      hydroxyethylthiamine diphosphate but not the transfer of electrons from this
      intermediate to O2. This intermediate form can be mimicked using 5-deaza-FAD,
      which is inactive toward O2 but active in an assay using 2,6
      dichlorophenolindophenol as electron acceptor. This analogue also promotes the
      rate constant of C2-H dissociation of thiamine diphosphate in pyruvate oxidase
      beyond the overall enzyme turnover. Formation of the catalytically competent FAD
      thiamine-pyruvate oxidase ternary complex requires a second step, which was
      detected at low temperature.

PMID- 9582327
TI  - Sp1 binds to the rat luteinizing hormone beta (LHbeta) gene promoter and mediates
      gonadotropin-releasing hormone-stimulated expression of the LHbeta subunit gene.
AB  - The hypothalamic hormone gonadotropin-releasing hormone (GnRH) plays a critical
      role in reproductive function by regulating the biosynthesis and secretion of the
      pituitary gonadotropins. Although it is known that GnRH induces luteinizing
      hormone beta (LHbeta) gene transcription, the mechanisms by which this occurs
      remain to be elucidated. We have shown previously that GH3 cells transfected with
      the rat GnRH receptor cDNA (GGH3-1' cells) support the expression of a
      cotransfected fusion gene composed of 797 base pairs of rat LHbeta gene 5'
      flanking sequence and the first 5 base pairs of the 5'-untranslated region fused
      to a luciferase reporter (-797/+5LHbetaLUC) and respond to a GnRH agonist with a
      10-fold stimulation of activity. Furthermore, we have shown that DNA sequences at
      -490/-352 confer GnRH responsiveness to the rat LHbeta gene. We have now
      identified two putative binding sites for Sp1, a three-zinc-finger transcription
      factor, within this region. Using electrophoretic mobility shift assay, DNase I
      footprinting, and methylation interference assays, we demonstrate that Sp1 can
      bind to these sites and that Sp1 is responsible for DNA-protein complexes formed
      using GGH3-1' and alphaT3-1 nuclear extracts. Mutations of the Sp1 binding sites,
      which block binding of Sp1, blunt the stimulation of the LHbeta gene promoter by
      GnRH. These data define GnRH-responsive elements in the LHbeta 5'-flanking
      sequence and suggest that Sp1 plays an important role in conferring GnRH
      responsiveness to the LHbeta subunit gene.

PMID- 9582326
TI  - Functional interactions among the subunits of replication factor C potentiate and
      modulate its ATPase activity.
AB  - Replication factor C (RF-C), a complex of five subunits, and several
      subassemblies of RF-C, representing intermediates along the proposed protein
      assembly pathway (Podust, V. N., and Fanning, E. (1997) J. Biol. Chem. 272, 6303
      6310), were expressed in insect cells using baculoviruses encoding individual
      subunits (p140, p40, p38, p37, and p36). Purified proteins were analyzed for
      ATPase activity to assess the role of individual subunits in ATP hydrolysis. His
      tagged p40 contained low ATPase activity, but tagged p37 and p36 did not.
      Complexes of p40.p37.p36 bearing a His tag on any subunit displayed DNA
      stimulated ATPase activity, in agreement with a recent report (Cai, J., Gibbs,
      E., Uhlmann, F., Philips, B., Yao, N., O'Donnell, M. , and Hurwitz, J. (1997) J.
      Biol. Chem. 272, 18974-18981). In contrast, complex p38.p37.p36-his displayed no
      ATPase, suggesting that p40 is essential for ATPase activity. Although p38 was
      not required for ATPase activity, the activity of the p40-his.p38.p37. p36
      complex was more salt-resistant than that of the p40-his.p37.p36 complex. The
      p140 subunit further increased the specific ATPase activity of RF-C complex by
      enhancing its stimulation by DNA. Taken together, the data indicate that all five
      RF-C subunits constitute ATPase activity, although the contributions of the
      individual subunits differ. Predicted ATP-binding domains of all five subunits
      were mutated to assess the importance of multiple ATP-binding sites of RF-C. In
      each case, the Lys of the conserved P-loop motif was replaced by Glu. The ATP
      binding domain of p38 was found to be dispensable for the activity of the five
      subunit RF-C in polymerase delta DNA synthesis. In contrast, mutation of the ATP
      binding domains in other RF-C subunits impaired RF-C assembly, function, or both.

PMID- 9582328
TI  - Characterization and cloning of a Dictyostelium Ste20-like protein kinase that
      phosphorylates the actin-binding protein severin.
AB  - After receiving an external stimulus Dictyostelium amoebae are able to rearrange
      their actin cytoskeleton within seconds, and phosphorylation is a prime candidate
      for quick modification of cytoskeletal components. We isolated a kinase from
      cytosolic extracts that specifically phosphorylated severin, a Ca2+-dependent F
      actin fragmenting protein. In gel filtration chromatography severin kinase eluted
      with a molecular mass of about 300 kDa and contained a 62-kDa component whose
      autophosphorylation caused a mobility shift in SDS-polyacrylamide gel
      electrophoresis and stimulated phosphorylation of severin. Severin kinase
      activity could be specifically precipitated with antibodies raised against the 62
      kDa polypeptide. Phosphorylation of severin was strongly reduced in the presence
      of Ca2+, indicating additional regulation at the substrate level. Peptide
      sequencing and cloning of the cDNA demonstrated that the 62-kDa protein belongs
      to the Ste20p- or p21-activated protein kinase family. It is most closely related
      to the germinal center kinase subfamily with its N-terminal positioned catalytic
      domain followed by a presumptive regulatory domain at the C terminus. The
      presence of a Ste20-like severin kinase in Dictyostelium suggests a direct signal
      transduction from the plasma membrane to the cytoskeleton by phosphorylation of
      actin-binding proteins.

PMID- 9582329
TI  - Generation and application of type-specific anti-heparan sulfate antibodies using
      phage display technology. Further evidence for heparan sulfate heterogeneity in
      the kidney.
AB  - Detailed analysis of various heparan sulfate (HS) species is seriously hampered
      by a lack of appropriate tools, such as antibodies. We adopted phage display
      technology to generate anti-HS antibodies. A "single pot" semisynthetic human
      antibody phage display library was subjected to four rounds of selection on HS
      from bovine kidney using panning methodology. Three different phage clones
      expressing anti-HS single chain variable fragment antibodies (HS4C3, HS4D10, and
      HS3G8) were isolated, with an amino acid sequence of the complementarity
      determining region 3 of GRRLKD (VH3 gene, DP-38), SLRMNGCGAHQ (VH3 gene, DP-42),
      and YYHYKVN (VH1 gene, DP-8), respectively. The antibodies react with HS and
      heparin, but not with DNA or other glycosaminoglycans. Kd values for HS are about
      0.1 microM. The three antibodies react differently toward various HS preparations
      and show different staining patterns on rat kidney sections, indicating
      recognition of different HS molecules. This also holds for two described mouse
      anti-HS IgMs (JM403 and 10E4; both generated by conventional hybridoma technique)
      and indicates the presence of at least 5 different HS species in the kidney. O-
      and N-sulfation are important for binding of HS to HS4C3 and HS3G8. The three
      single chain antibodies, but not JM403, block a basic fibroblast growth factor
      binding site of HS. It is concluded that phage display technology presents a
      powerful technique to generate antibodies specific for HS epitopes. This is the
      first time this technique has been successfully applied to obtain directly
      antibodies to (poly)saccharides.

PMID- 9582330
TI  - Arrestin-independent internalization of the m1, m3, and m4 subtypes of muscarinic
      cholinergic receptors.
AB  - To understand what processes contribute to the agonist-induced internalization of
      subtypes of muscarinic acetylcholine receptors, we analyzed the role of
      arrestins. Whereas the m2 mAChR has been shown to undergo augmented
      internalization when arrestins 2 and 3 are overexpressed (Pals-Rylaarsdam, R.,
      Gurevich, V. V., Lee, K. B., Ptasienski, J. A., Benovic, J. L., and Hosey, M. M.
      (1997) J. Biol. Chem. 272, 23682-23689), the agonist-induced internalization of
      m1, m3, and m4 mAChRs was unchanged when arrestins 2 or 3 were overexpressed in
      transiently transfected HEK-tsA201 cells. Furthermore, when a dominant-negative
      arrestin was used to interrupt endogenous arrestin function, there was no change
      in the internalization of the m1, m3, and m4 mAChR whereas the internalization of
      the beta2 adrenergic receptor was completely blocked. Wild-type and GTPase
      deficient dominant-negative dynamin were used to determine which endocytic
      machinery played a role in the endocytosis of the subtypes of mAChRs.
      Interestingly, when dynamin function was blocked by overexpression of the GTPase
      deficient dynamin, agonist- induced internalization of the the m1, m3, and m4
      mAChRs was suppressed. These results suggested that the internalization of the
      m1, m3, and m4 mAChRs occurs via an arrestin-independent but dynamin-dependent
      pathway. To ascertain whether domains that confer arrestin sensitivity and
      dynamin insensitivity could be functionally exchanged between subtypes of mAChRs,
      chimeric m2/m3 receptors were analyzed for their properties of agonist-induced
      internalization. The results demonstrated that the third intracellular loop of
      the m2 mAChR conferred arrestin sensitivity and dynamin insensitivity to the
      arrestin-insensitive, dynamin-sensitive m3 mAChR while the analogous domain of
      the m3 mAChR conferred arrestin resistance and dynamin sensitivity to the
      previously arrestin-sensitive, dynamin-insensitive m2 mAChR.

PMID- 9582331
TI  - Characterization of the gene encoding the human Kidd blood group/urea transporter
      protein. Evidence for splice site mutations in Jknull individuals.
AB  - The Kidd (JK) blood group is carried by an integral membrane glycoprotein which
      transports urea through the red cell membrane and is also present on endothelial
      cells of the vasa recta in the kidney. The exon-intron structure of the human
      blood group Kidd/urea transporter gene has been determined. It is organized into
      11 exons distributed over 30 kilobase pairs. The mature protein is encoded by
      exons 4-11. The transcription initiation site was identified by 5'-rapid
      amplification of cDNA ends-polymerase chain reaction at 335 base pairs upstream
      of the translation start point located in exon 4. The 5'-flanking region, from
      nucleotide -837 to -336, contains TATA and inverted CAAT boxes as well as GATA
      1/SP1 erythroid-specific cis-acting regulatory elements. Analysis of the 3'
      untranslated region reveals that the two equally abundant erythroid transcripts
      of 4.4 and 2.0 kilobase pairs arise from usage of different alternative
      polyadenylation signals. No obvious abnormality of the Kidd/urea transporter
      gene, including the 5'- and 3'-untranslated regions, has been detected by
      Southern blot analysis of the blood of two unrelated Jknull individuals (B.S. and
      L.P.), which lacks all Jk antigens and Jk proteins on red cells, but was
      genotyped as homozygous for a "silent" Jkb allele. Further analysis indicated
      that different splice site mutations occurred in each variant. The first mutation
      affected the invariant G residue of the 3'-acceptor splice site of intron 5
      (variant B.S.), while the second mutation affected the invariant G residue of the
      5'-donor splice site of intron 7 (variant L.P.). These mutations caused the
      skipping of exon 6 and 7, respectively, as seen by sequence analysis of the Jk
      transcripts present in reticulocytes. Expression studies in Xenopus oocytes
      demonstrated that the truncated proteins encoded by the spliced transcripts did
      not mediate a facilitated urea transport compared with the wild type Kidd/urea
      transporter protein and were not expressed on the oocyte's plasma membrane. These
      findings provide a rational explanation for the lack of Kidd/urea transporter
      protein and defect in urea transport of Jknull cells.

PMID- 9582332
TI  - Structure-function analysis of CALX1.1, a Na+-Ca2+ exchanger from Drosophila.
      Mutagenesis of ionic regulatory sites.
AB  - Cytoplasmic Na+ and Ca2+ regulate the activity of Na+-Ca2+ exchange proteins, in
      addition to serving as the transported ions, and protein regions involved in
      these processes have been identified for the canine cardiac Na+-Ca2+ exchanger,
      NCX1.1. Although protein regions associated with Na+i- and Ca2+i-dependent
      regulation are highly conserved among cloned Na+-Ca2+ exchangers, it is unknown
      whether or not the structure-function relationships characteristic of NCX1.1
      apply to any other exchangers. Therefore, we studied structure-function
      relationships in a Na+-Ca2+ exchanger from Drosophila, CALX1.1, which is unique
      among characterized members of this family of proteins in that microM levels of
      Ca2+i inhibit exchange current. Wild-type and mutant CALX1.1 exchangers were
      expressed in Xenopus oocytes and characterized electrophysiologically using the
      giant excised patch technique. Mutations within the putative regulatory Ca2+i
      binding site of CALX1. 1, like corresponding alterations in NCX1.1, led to
      reduced ability (i.e. D516V and D550I) or inability (i.e. G555P) of Ca2+i to
      inhibit Na+-Ca2+ exchange activity. Similarly, mutations within the putative XIP
      region of CALX1.1, as in NCX1.1, led to two distinct phenotypes: acceleration
      (i.e. K306Q) and elimination (i.e. Delta310-313) of Na+i-dependent inactivation.
      These results indicate that the respective regulatory roles of the Ca2+i binding
      site and XIP region are conserved between CALX1.1 and NCX1.1, despite opposite
      responses to Ca2+i. We extended these findings using chimeric constructs of
      CALX1.1 and NCX1.1 to determine whether or not functional interconversion of
      Ca2+i regulatory phenotypes was feasible. With one chimera (i.e. CALX:NCX:CALX),
      substitution of a 193-amino acid segment, from the large intracellular loop of
      NCX1.1, for the corresponding 177-amino acid segment of CALX1.1 led to an
      exchanger that was stimulated by Ca2+i. This result indicates that the regulatory
      Ca2+i binding site of NCX1.1 retains function in a CALX1. 1 parent transporter
      and that the substituted segment contains some of the amino acid sequence(s)
      required for transduction of the Ca2+i binding signal.

PMID- 9582333
TI  - Direct identification of a second distinct site of contact between
      cholecystokinin and its receptor.
AB  - We have developed a biologically active analogue of cholecystokinin (CCK) that
      incorporates a photolabile benzoylphenylalanine (Bpa) moiety in the middle of its
      pharmacophoric domain, which efficiently establishes a covalent bond with an
      interacting domain of the CCK receptor. This probe incorporated L-Bpa in the
      position of Gly29 of the well characterized, radioiodinatable CCK analogue, D-Tyr
      Gly-[(Nle28,31)CCK-26-33]. It was a potent pancreatic secretagogue (EC50 = 28 +/-
      6 nM) that was equally efficacious with natural CCK, and bound to the CCK
      receptor with moderate affinity (IC50 = 450 +/- 126 nM). This was adequate to
      allow specific covalent labeling of the receptor. The labeled domain was within
      the cyanogen bromide fragment of the receptor including the top of TM6 (the sixth
      transmembrane domain), the third extracellular loop, and TM7 (the seventh
      transmembrane domain), as proven by direct Edman degradation sequencing. When
      this fragment was modified by the replacement of Val342 with Met to generate an
      additional site of cyanogen bromide cleavage, the labeled fragment was reduced in
      apparent size consistent with its representing the carboxyl-terminal portion of
      this fragment. Radiochemical sequencing of that fragment demonstrated covalent
      attachment of the probe to His347 and Leu348 in this domain. This represents the
      second experimentally demonstrated contact between a CCK analogue and this
      receptor, complementing the labeling of the domain just above TM1 (the first
      transmembrane domain) by a photolabile residue at the carboxyl terminus of CCK
      (Ji, Z. S., Hadac, E. M., Henne, R. M., Patel, S. A., Lybrand, T. P., and Miller,
      L. J. (1997) J. Biol. Chem. 272, 24393-24401). Both contacts are consistent with
      the conformational model of CCK binding proposed on the basis of the initial
      contact.

PMID- 9582334
TI  - Role of the S3 stalk segment in the thapsigargin concentration dependence of
      sarco-endoplasmic reticulum Ca2+ ATPase inhibition.
AB  - The sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) is specifically inhibited by
      thapsigargin (TG), whereas the Na+,K+-ATPase is not. Large chimeric exchanges
      between Ca2+ and Na+,K+-ATPases (Norregaard, A., Vilsen, B., and Andersen, J. P.
      (1994) J. Biol. Chem. 269, 26598-26601), as well as photolabeling with a TG azido
      derivative (Hua, S., and Inesi, G. (1997) Biochemistry 36, 11865-11872), suggest
      that the S3-M3 (stalk and membrane-bound) region of the Ca2+ ATPase is involved
      in TG binding. We produced small site-directed changes in the S3 stalk segment of
      the Ca2+ ATPase and found that mutation of five amino acids to the corresponding
      Na+,K+-ATPase residues increases by 3 orders of magnitude the TG concentration
      required for inhibition of Ca2+ ATPase and coupled Ca2+ transport. A single
      mutation in the S3 stalk segment (Gly257 --> Ile) is sufficient to increase by 1
      order of magnitude the TG concentration required to produce 50% inhibition. By
      comparison, mutations yielding a nine-amino acid homology in the M3 transmembrane
      segment, or a 25-amino acid homology in the S4 stalk segment, do not affect the
      ATPase sensitivity to TG. We suggest that specific binding of TG to the S3 stalk
      segment, in addition to stacking of the TG ring structure at the membrane
      interface, determines the high affinity of the ATPase for the inhibitor.

PMID- 9582335
TI  - Aggrecan synthesis and secretion. A paradigm for molecular and cellular
      coordination of multiglobular protein folding and intracellular trafficking.
AB  - Each globular domain of exported multiglobular proteins putatively undergoes
      chaperone surveillance in the endoplasmic reticulum lumen. It is difficult to
      visualize how surveillance of multiple globular domains might be orchestrated and
      regulated. Aggrecan core protein has been used as a prototype for this problem by
      examining transfection of informative constructs into Chinese hamster ovary
      cells. The salient results are as follows: 1) aggrecan's N-terminal G1 domain is
      minimally secreted, and its flanking Golgi reporter sites are not decorated with
      glycsoaminoglycan chains; in contrast, its C-terminal G3 domain is readily
      secreted with flanking GAG chains, and G3 also facilitates G1 secretion; 2) G3
      but not G1 can be intracellularly cross-linked to chaperone Hsp25; 3) G3 and
      Hsp25 remain noncovalently bound and are secreted together when G3 is situated N
      terminal to its normal location; 4) exon 15, which encodes the center of G3's C
      lectin subdomain, is necessary and sufficient for G3 secretion. A model is
      proposed in which Hsp25 piggybacks onto nascent G3 in the cytosol during a
      translocational pause and enters the ER lumen with G3, and once G3 properly
      folds, Hsp25 releases G3 and recycles to the nucleus while G3 continues to the
      Golgi stacks, providing passage for the entire core protein.

PMID- 9582336
TI  - Fibroblast growth factor receptor 3 mutations promote apoptosis but do not alter
      chondrocyte proliferation in thanatophoric dysplasia.
AB  - Thanatophoric dysplasia (TD) is a lethal skeletal disorder caused by recurrent
      mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene. The mitogenic
      response of fetal TD I chondrocytes in primary cultures upon stimulation by
      either FGF 2 or FGF 9 did not significantly differ from controls. Although the
      levels of FGFR 3 mRNAs in cultured TD chondrocytes were similar to controls, an
      abundant immunoreactive material was observed at the perinuclear level using an
      anti-FGFR 3 antibody in TD cells. Transduction signaling via the mitogen
      activated protein kinase pathway was assessed by measuring extracellular signal
      regulated kinase activity (ERK 1 and ERK 2). Early ERKs activation following FGF
      9 supplementation was observed in TD chondrocytes (2 min) as compared with
      controls (5 min) but no signal was detected in the absence of ligand. By contrast
      ligand-independent activation of the STAT signaling pathway was demonstrated in
      cultured TD cells and confirmed by immunodetection of Stat 1 in the nuclei of
      hypertrophic TD chondrocytes. Moreover, the presence of an increased number of
      apoptotic chondrocytes in TD fetuses was associated with a higher expression of
      Bax and the simultaneous decrease of Bcl-2 levels. Taken together, these results
      indicate that FGFR 3 mutations in TD I fetuses do not hamper chondrocyte
      proliferation but rather alter their differentiation by triggering premature
      apoptosis through activation of the STAT signaling pathway.

PMID- 9582337
TI  - The human poly(A)-binding protein 1 shuttles between the nucleus and the
      cytoplasm.
AB  - We have studied the intracellular localization of poly(A)-binding protein 1
      (PABP1) by indirect immunofluorescence as well as by tagging with the green
      fluorescent protein (GFP) in living cells. We show that PABP1 is able to enter
      the nucleus. Accumulation of PABP1 in the nuclei was observed upon transcription
      inhibition, suggesting that active transcription is required for PABP1 export.
      The nuclear import of PABP1 is an energy-dependent process since PABP1 fails to
      enter the nucleus upon ATP depletion and at low temperature. Transfection of
      PABP1 or PABP1-GFP resulted in heterogeneity of intracellular distribution of the
      protein. In the low expressing cells, PABP1 was localized in the cytoplasm,
      whereas in the high expressors, we observed accumulation of the protein in the
      nucleus. Nuclear PABP1 observed either after overexpression or after
      transcription inhibition was found in speckles and colocalized with splicing
      factor SC35. The ability of PABP1 to shuttle between nucleus and cytoplasm was
      also shown by heterokaryon formation upon cell fusion. Deletion mutagenesis
      showed that the minimal part of PABP1 retaining the ability to shuttle consists
      of the first two RNA-binding domains. This mutant interacted with poly(A) RNA
      with high affinity and accumulated in the nucleus. Deletion mutants exhibiting
      reduced RNA binding affinity did not accumulate in the nucleus. PABP1 has been
      proposed to participate at various steps of mRNA utilization. Our results suggest
      involvement of PABP1 in nuclear events associated with the formation and
      transport of mRNP to the cytoplasm and identify a new trafficking pattern for RNA
      binding proteins.

PMID- 9582338
TI  - Solution structure of a syndecan-4 cytoplasmic domain and its interaction with
      phosphatidylinositol 4,5-bisphosphate.
AB  - Syndecan-4, a transmembrane heparan sulfate proteoglycan, is a coreceptor with
      integrins in cell adhesion. It has been suggested to form a ternary signaling
      complex with protein kinase Calpha and phosphatidylinositol 4,5-bisphosphate
      (PIP2). Syndecans each have a unique, central, and variable (V) region in their
      cytoplasmic domains, and that of syndecan-4 is critical to its interaction with
      protein kinase C and PIP2. Two oligopeptides corresponding to the variable region
      (4V) and whole domain (4L) of syndecan-4 cytoplasmic domain were synthesized for
      nuclear magnetic resonance (NMR) studies. Data from NMR and circular dichroism
      indicate that the cytoplasmic domain undergoes a conformational transition and
      forms a symmetric dimer in the presence of phospholipid activator PIP2. The
      solution conformations of both free and PIP2-complexed 4V have been determined by
      two-dimensional NMR spectroscopy and dynamical simulated annealing calculations.
      The 4V peptide in the presence of PIP2 formed a compact dimer with two twisted
      strands packed parallel to each other and the exposed surface of the dimer
      consisted of highly charged and polar residues. The overall three-dimensional
      structure in solution exhibits a twisted clamp shape having a cavity in the
      center of dimeric interface. In addition, it has been observed that the syndecan
      4V strongly interacts not only with fatty acyl groups but also the anionic head
      group of PIP2. These findings reveal that PIP2 promotes oligomerization of
      syndecan-4 cytoplasmic domain for transmembrane signaling and cell-matrix
      adhesion.

PMID- 9582339
TI  - Identification of a novel p53 functional domain that is necessary for mediating
      apoptosis.
AB  - The ability of p53 to induce apoptosis requires its sequence-specific DNA binding
      activity; however, the transactivation-deficient p53(Gln22-Ser23) can still
      induce apoptosis. Previously, we have shown that the region between residues 23
      and 97 in p53 is necessary for such activity. In an effort to more precisely map
      a domain necessary for apoptosis within the N terminus, we found that deletion of
      the N-terminal 23 amino acids compromises, but does not abolish, p53 induction of
      apoptosis. Surprisingly, p53(Delta1-42), which lacks the N-terminal 42 amino
      acids and the previously defined activation domain, retains the ability to induce
      apoptosis to an even higher level than wild-type p53. A more extensive deletion,
      which eliminates the N-terminal 63 amino acids, renders p53 completely inert in
      mediating apoptosis. In addition, we found that both p53(Delta1-42) and p53(Gln22
      Ser23) can activate a subset of cellular p53 targets. Furthermore, we showed that
      residues 53 and 54 are critical for the apoptotic and transcriptional activities
      of both p53(Delta1-42) and p53(Gln22-Ser23). Taken together, these data suggest
      that within residues 43-63 lie an apoptotic domain as well as another
      transcriptional activation domain. We therefore postulate that the apoptotic
      activity in p53(Gln22-Ser23) and p53(Delta1-42) is still transcription-dependent.

PMID- 9582340
TI  - Identification of a nickel(II) binding site on hemoglobin which confers
      susceptibility to oxidative deamination and intramolecular cross-linking.
AB  - Complexation of Ni(II) with native state recombinant hemoglobin is shown to
      produce NH2-terminal deamination and globin cross-linking in the presence of the
      oxidant potassium peroxymonosulfate (OxoneTM). Both the oxidative deamination and
      cross-linking are exclusive to the beta chains. Recombinant hemoglobin mutants
      have been created to identify protein sequence requirements for these reactions.
      It was found that His-2 of the beta globin is required for redox active Ni(II)
      complexation, oxidative deamination, and cross-linking. The oxidative deamination
      results in the formation of a free carbonyl in place of the NH2-terminal amine of
      the beta chain. Most cross-linking of the beta globin occurs intramolecularly,
      forming beta globin dimers. Structural characterization of the beta globin dimers
      indicates the presence of heterogeneous cross-links within the central hemoglobin
      cavity between the NH2 terminus of one beta chain and the COOH-terminal region of
      the other.

PMID- 9582341
TI  - X-ray crystal structure of the human galectin-3 carbohydrate recognition domain
      at 2.1-A resolution.
AB  - Galectins are a family of lectins which share similar carbohydrate recognition
      domains (CRDs) and affinity for small beta-galactosides, but which show
      significant differences in binding specificity for more complex glycoconjugates.
      We report here the x-ray crystal structure of the human galectin-3 CRD, in
      complex with lactose and N-acetyllactosamine, at 2.1-A resolution. This structure
      represents the first example of a CRD determined from a galectin which does not
      show the canonical 2-fold symmetric dimer organization. Comparison with the
      published structures of galectins-1 and -2 provides an explanation for the
      differences in carbohydrate-binding specificity shown by galectin-3, and for the
      fact that it fails to form dimers by analogous CRD-CRD interactions.

PMID- 9582342
TI  - Smad-dependent transcriptional activation of human type VII collagen gene
      (COL7A1) promoter by transforming growth factor-beta.
AB  - We have previously shown that transforming growth factor-beta (TGF-beta)
      increases type VII collagen gene (COL7A1) expression in human dermal fibroblasts
      in culture (Mauviel, A., Lapiere, J.-C., Halcin, C., Evans, C. H., and Uitto, J.
      (1994) J. Biol. Chem. 269, 25-28). To gain insight into the molecular mechanisms
      underlying the up-regulation of COL7A1 by this growth factor, we performed
      transient cell transfections with a series of 5'-deletion
      promoter/chloramphenicol acetyltransferase reporter gene constructs. We
      identified a 68-base pair region between nucleotides -524 and -456, relative to
      the transcription start site, as critical for TGF-beta response. Using
      electrophoresis mobility shift assays (EMSAs) with an oligonucleotide spanning
      the region from -524 to -444, we discovered that a TGF-beta-specific protein-DNA
      complex was formed as early as 11 min after TGF-beta stimulation and persisted
      for 1 h after addition of the growth factor. Deletion analysis of the TGF
      betaresponsive region of the COL7A1 promoter by EMSA identified segment -496/-444
      as the minimal fragment capable of binding the TGF-beta-induced complex.
      Furthermore, two distinct segments, -496/-490 and -453/-444, appeared to be
      necessary for TGF-beta-induced DNA binding activity, suggesting a bipartite
      element. Supershift experiments with a pan-Smad antibody unambiguously identified
      the TGF-beta-induced complex as containing a Smad member. This is the first
      direct identification of binding of endogenous Smad proteins to regulatory
      sequences of a human gene.

PMID- 9582343
TI  - Murine cell line SX9 bearing a mutation in the dna-pkcs gene exhibits aberrant
      V(D)J recombination not only in the coding joint but also in the signal joint.
AB  - We established the radiosensitive cell line SX9 from mammary carcinoma cell line
      FM3A. In SX9 cells a defect of DNA-dependent protein kinase (DNA-PK) activity was
      suggested. Additionally, a complementation test suggested that the SX9 cell line
      belongs to a x-ray cross-complementing group (XRCC) 7. Isolation and sequence
      analyses of DNA-dependent protein kinase catalytic subunit (dna-pkcs) cDNA in SX9
      cells disclosed nucleotide "T" (9572) to "C" transition causing substitution of
      amino acid residue leucine (3191) to proline. Interestingly, the mutation occurs
      in one allele, and transcripts of the dna-pkcs expressed exclusively from mutated
      allele. V(D)J recombination assay using extrachromosomal vector revealed the
      defects of not only coding but also signal joint formation. The frequency of the
      signal joint decreased to approximately one-tenth and the fidelity drastically
      decreased to 12. 2% as compared with the normal cell line. To confirm the
      responsibility of the dna-pkcs gene for abnormal V(D)J recombination in SX9, the
      full-length dna-pkcs gene was introduced into SX9. As a result, restoration of
      V(D)J recombination by wild type dna-pkcs cDNA was observed. SX9 is a novel dna
      pkcs-deficient cell line.

PMID- 9582344
TI  - Rapid degradation of short-chain acyl-CoA dehydrogenase variants with temperature
      sensitive folding defects occurs after import into mitochondria.
AB  - Most disease-causing missense mutations in short-chain acyl-CoA dehydrogenase
      (SCAD) and medium-chain acyl-CoA dehydrogenase are thought to compromise the
      mitochondrial folding and/or stability of the mutant proteins. To address this
      question, we studied the biogenesis of SCAD proteins in COS-7 cells transfected
      with cDNA corresponding to two SCAD missense mutations, R22W (identified in a
      patient with SCAD deficiency) or R22C (homologous to a disease-associated R28C
      mutation in medium-chain acyl-CoA dehydrogenase deficiency). After cultivation at
      37 degreesC the steady-state amounts of SCAD antigen and activity in extracts
      from cells transfected with mutant SCAD cDNAs were negligible compared with those
      of cells transfected with SCAD wild type cDNA, documenting the deleterious effect
      of the two mutations. Analysis of metabolically labeled and immunoprecipitated
      SCAD wild type and mutant proteins showed that the two mutant proteins were
      synthesized as the 44-kDa precursor form, imported into mitochondria and
      processed to the mature 41.7-kDa form in a normal fashion. However, the
      intramitochondrial level of matured mutant SCAD proteins decreased rapidly to
      very low levels, indicating a rapid degradation of the mutant proteins at 37
      degreesC. A rapid initial elimination phase was also observed following
      cultivation at 26 degreesC; however, significantly higher amounts of
      metabolically labeled and immunoprecipitated mature mutant SCAD proteins remained
      detectable. This corresponds well with the appreciable steady-state levels of
      SCAD mutant enzyme activity observed at 26 degreesC. In addition, confocal laser
      scanning microscopy of immunostained cells showed that the SCAD mutant proteins
      were localized intramitochondrially. Together, these results show that newly
      synthesized SCAD R22W and R22C mutant proteins are imported and processed in the
      mitochondrial matrix, but that a fraction of the proteins is rapidly eliminated
      by a temperature-dependent degradation mechanism. Thermal stability profiles of
      wild type and mutant enzymes revealed no difference between the two mutants and
      the wild type protein. Furthermore, the turnover of the SCAD mutant enzymes in
      intact cells was comparable to that of the wild type, indicating that the rapid
      degradation of the mutant SCAD proteins is not due to lability of the correctly
      folded tetrameric structure but rather to elimination of partly folded or
      misfolded proteins along the folding pathway.

PMID- 9582345
TI  - Manganese lipoxygenase. Purification and characterization.
AB  - A linoleic acid (13R)-lipoxygenase was purified to homogeneity from the culture
      medium of Gaumannomyces graminis, the take-all fungus, by hydrophobic
      interaction, cation exchange, lectin affinity, and size-exclusion chromatography.
      The purified dioxygenase lacked light absorption between 300 and 700 nm. Gel
      filtration indicated an apparent molecular mass of approximately 135 kDa in 6 M
      urea and approximately 160 kDa in buffer. SDS-polyacrylamide gel electrophoresis
      (PAGE) showed that the enzyme was heterogeneous in size and consisted of diffuse
      protein bands of 100-140 kDa. Treatment with glycosidases for N- and O-linked
      oligosaccharides yielded a distinct protein of approximately 73 kDa on SDS-PAGE.
      Atomic emission spectroscopy indicated 0.5-1.0 manganese atom/enzyme molecule.
      The isoelectric point was approximately 9.7, and the enzyme was active between pH
      5 and 11 with optimum activity at pH 7. 0. For molecular oxygen, Km was 30 microM
      and Vmax 10 micromol mg-1min-1; for linoleic acid, Km was 4.4 micromol, Vmax 8.2
      micromol mg-1min-1, and the turnover number 1100 min-1. The enzyme oxidized
      linolenic acid twice as fast as linoleic acid. The main products were identified
      by mass spectrometry as 13-hydroperoxy-(9Z,11E, 15Z)-octadecatrienoic and 13
      hydroperoxy-(9Z,11E)-octadecadienoic acids, respectively. After reduction of the
      hydroperoxide, steric analysis of methyl 13-hydroxyoctadecadienoate by chiral
      high performance liquid chromatography yielded one enantiomer (>95%), which co
      eluted with the R-stereoisomer of methyl (13R, 13S)-hydroxyoctadecadienoate.
      Arachidonic and dihomogammalinolenic acids were not substrates, while oxygen
      consumption, UV analysis, and mass spectrometric analysis indicated that gamma
      linolenic acid was oxygenated both at C-11 and C-13. The enzyme was active at 60
      degreesC and after treatment with 6 M urea. It was strongly inhibited by 10-50
      microM concentrations of eicosatetraynoic acid and a lipoxygenase inhibitor (N-(3
      phenoxycinnamyl)acetohydroxamic acid), but many other lipoxygenase inhibitors
      (100 microM) were without effect. We conclude that, after deglycosylation, the
      enzyme has the same size on SDS-PAGE as mammalian and marine lipoxygenases, but
      it differs from all previously described lipoxygenases in three ways. It is
      secreted, it forms (13R)-hydroperoxy-(9Z, 11E)-octadecadienoic acid, and it
      contains manganese.

PMID- 9582346
TI  - Manganese lipoxygenase. Discovery of a bis-allylic hydroperoxide as product and
      intermediate in a lipoxygenase reaction.
AB  - Linoleic acid was incubated with manganese lipoxygenase (Mn-LO) from the fungus
      Gaumannomyces graminis. The product consisted of (13R)-hydroperoxy-(9Z,11E)
      octadecadienoic acid ((13R)-HPOD) and a new hydroperoxide, (11S)-hydroperoxy
      (9Z,12Z)-octadecadienoic acid ((11S)-HPOD). Incubation of (11R)-[2H]- and (11S)
      [2H]linoleic acids with Mn-LO led to the formation of hydroperoxides that largely
      retained and lost, respectively, the deuterium label. Conversion of the (11S)
      deuteriolinoleic acid was accompanied by a primary isotope effect, which
      manifested itself in a strongly reduced rate of formation of hydroperoxides and
      in a time-dependent accumulation of deuterium in the unconverted substrate. These
      experiments indicated that the initial step catalyzed by Mn-LO consisted of
      abstraction of the pro-S hydrogen of linoleic acid to produce a linoleoyl
      radical. (11S)-HPOD was converted into (13R)-HPOD upon incubation with Mn-LO. The
      mechanism of this enzyme-catalyzed hydroperoxide rearrangement was studied in
      experiments carried out with 18O2 gas or 18O2-labeled hydroperoxides. Incubation
      of [11-18O2](11S)-HPOD with Mn-LO led to the formation of (13R)-HPOD, which
      retained 39-44% of the 18O label, whereas (11S)-HPOD incubated with Mn-LO under
      18O2 produced (13R)-HPOD, which had incorporated 57% of 18O. Furthermore,
      analysis of the isotope content of (11S)-HPOD remaining unconverted in such
      incubations demonstrated that [11-18O2](11S)-HPOD suffered a time-dependent loss
      of 18O when exposed to Mn-LO, whereas (11S)-HPOD incorporated 18O when incubated
      with Mn-LO under 18O2. On the basis of these experiments, it was proposed that
      the conversion of (11S)-HPOD into (13R)-HPOD occurred in a non-concerted way by
      deoxygenation into a linoleoyl radical. Subsequent reoxygenation of this
      intermediate by dioxygen attack at C-13 produced (13R)-HPOD, whereas attack at C
      11 regenerated (11S)-HPOD. The hydroperoxide rearrangement occurred by oxygen
      rebound, although, as demonstrated by the 18O experiments, the oxygen molecule
      released from (11S)-HPOD exchanged with surrounding molecular oxygen prior to its
      reincorporation.

PMID- 9582347
TI  - Expression and purification of the extracellular ligand binding region of
      metabotropic glutamate receptor subtype 1.
AB  - Each metabotropic glutamate receptor possesses a large extracellular domain that
      consists of a sequence homologous to the bacterial periplasmic binding proteins
      and a cysteine-rich region. Previous experiments have proposed that the
      extracellular domain is responsible for ligand binding. However, it is currently
      unknown whether the extracellular ligand binding site can bind ligands without
      other domains of the receptor. We began by obtaining a sufficient amount of
      receptor protein on a baculovirus expression system. In addition to the transfer
      vector that encodes the entire coding region, transfer vectors that encode
      portions of the extracellular domain were designed. Here, we report a soluble
      metabotropic glutamate receptor that encodes only the extracellular domain and
      retains a ligand binding characteristic similar to that of the full-length
      receptor. The soluble receptor secreted into culture medium showed a dimerized
      form. Furthermore, we have succeeded in purifying it to homogeneity. Dose
      response curves of agonists for the purified soluble receptor were examined. The
      effective concentration for half-maximal inhibition (IC50) of quisqualate for the
      soluble receptor was 3.8 x 10(-8) M, which was comparable to that for the full
      length receptor. The rank order of inhibition of the agonists was quisqualate >>
      ibotenate >/= L-glutamate approximately (1S,3R)-1-aminocyclopentane-1, 3
      dicarboxylic acid. These data demonstrate that a ligand binding event in
      metabotropic glutamate receptors can be dissociated from the membrane domain.

PMID- 9582348
TI  - Sp1 cooperates with the ets transcription factor, GABP, to activate the CD18
      (beta2 leukocyte integrin) promoter.
AB  - CD18, the beta chain of the leukocyte integrins, plays a crucial role in immune
      and inflammatory responses. CD18 is expressed exclusively by leukocytes, and it
      is transcriptionally regulated during the differentiation of myeloid cells. The
      ets factors, PU.1 and GABP, bind to three ets sites in the CD18 promoter, which
      are essential for high level myeloid expression of CD18. We now identify two
      binding sites for the transcription factor, Sp1, that flank these ets sites. Sp1
      is the only factor from myeloid cells that binds to these sites in a sequence
      specific manner. Mutagenesis of these sites abrogates Sp1 binding and
      significantly reduces the activity of the transfected CD18 promoter in myeloid
      cells. Transfection of Sp1 into Drosophila Schneider cells, which otherwise lack
      Sp1, activates the CD18 promoter dramatically. GABP also activates the CD18
      promoter in Schneider cells. Co-transfection of Sp1 and GABP activates CD18 more
      than the sum of their individual effects, indicating that these factors cooperate
      to transcriptionally activate myeloid expression of CD18. These studies support a
      model of high level, lineage-restricted gene expression mediated by cooperative
      interactions between widely expressed transcription factors.

PMID- 9582349
TI  - Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding
      protein.
AB  - All eukaryotic mRNAs (except organellar) are capped at their 5' end. The cap
      structure (m7GpppN, where N is any nucleotide) is extremely important for the
      processing and translation of mRNA. Several cap-binding proteins that facilitate
      these processes have been characterized. Here we describe a novel human
      cytoplasmic protein that is 30% identical and 60% similar to the human
      translation initiation factor 4E (eIF4E). We demonstrate that this protein, named
      4E Homologous Protein (4EHP), binds specifically to capped RNA in an ATP- and
      divalent ion-independent manner. The three-dimensional structure of 4EHP, as
      predicted by homology modeling, closely resembles that of eIF4E and site-directed
      mutagenesis analysis of 4EHP strongly suggests that it shares with eIF4E a common
      mechanism for cap binding. A putative function for 4EHP is discussed.

PMID- 9582350
TI  - Impaired assembly of E1 decarboxylase of the branched-chain alpha-ketoacid
      dehydrogenase complex in type IA maple syrup urine disease.
AB  - The E1 decarboxylase component of the human branched-chain ketoacid dehydrogenase
      complex comprises two E1alpha (45.5 kDa) and two E1beta (37.5 kDa) subunits
      forming an alpha2 beta2 tetramer. In patients with type IA maple syrup urine
      disease, the E1alpha subunit is affected, resulting in the loss of E1 and
      branched-chain ketoacid dehydrogenase catalytic activities. To study the effect
      of human E1alpha missense mutations on E1 subunit assembly, we have developed a
      pulse-chase labeling protocol based on efficient expression and assembly of human
      (His)6-E1alpha and untagged E1beta subunits in Escherichia coli in the presence
      of overexpressed chaperonins GroEL and GroES. Assembly of the two 35S-labeled E1
      subunits was indicated by their co-extraction with Ni2+-nitrilotriacetic acid
      resin. The nine E1alpha maple syrup urine disease mutants studied showed aberrant
      kinetics of assembly with normal E1beta in the 2-h chase compared with the wild
      type and can be classified into four categories of normal (N222S-alpha and R220W
      alpha), moderately slow (G245R-alpha), slow (G204S-alpha, A240P-alpha, F364C
      alpha, Y368C-alpha, and Y393N-alpha), and no (T265R-alpha) assembly. Prolonged
      induction in E. coli grown in the YTGK medium or lowering of induction
      temperature from 37 to 28 degreesC (in the case of T265R-alpha), however,
      resulted in the production of mutant E1 proteins. Separation of purified E1
      proteins by sucrose density gradient centrifugation showed that the wild-type E1
      existed entirely as alpha2 beta2 tetramers. In contrast, a subset of E1alpha
      missense mutations caused the occurrence of exclusive alphabeta dimers (Y393N
      alpha and F364C-alpha) or of both alpha2beta2 tetramers and lower molecular
      weight species (Y368C-alpha and T265R-alpha). Thermal denaturation at 50 degreesC
      indicated that mutant E1 proteins aggregated more rapidly than wild type (rate
      constant, 0.19 min-1), with the T265R-alpha mutant E1 most severely affected
      (rate constant, 4.45 min-1). The results establish that the human E1alpha
      mutations in the putative thiamine pyrophosphate-binding pocket that are studied,
      with the exception of G204S-alpha, have no effect on E1 subunit assembly. The
      T265R-alpha mutation adversely impacts both E1alpha folding and subunit
      interactions. The mutations involving the C-terminal aromatic residues impede
      both the kinetics of subunit assembly and the formation of the native alpha2
      beta2 structure.

PMID- 9582351
TI  - Regulation of protein phosphatase 2A activity by caspase-3 during apoptosis.
AB  - Although the available evidence suggests that whereas the caspase family plays a
      major role in apoptosis, they are not the sole stimulators of death. A random
      yeast two-hybrid screen of a lymphocyte cDNA library (using caspase-3 as the
      bait) found an interaction between caspase-3 and the regulatory subunit Aalpha of
      protein phosphatase 2A. This protein was found to be a substrate for caspase-3,
      but not caspase-1, and could compete effectively against either a protein or
      synthetic peptide substrate. In Jurkat cells induced to undergo apoptosis with
      anti-Fas antibody, protein phosphatase 2A (PP2A) activity increased 4.5-fold
      after 6 h. By 12 h, the regulatory Aalpha subunit could no longer be detected in
      cell lysates. There was no change in the amount of the catalytic subunit. The
      effects on PP2A could be prevented by the caspase family inhibitors acetyl-Asp
      Glu-Val-Asp (DEVD) aldehyde or Ac-DEVD fluoromethyl ketone. The mitogen-activated
      protein (MAP) kinase pathway is regulated by PP2A. At 12 h after the addition of
      anti-Fas antibody, a decrease in the amount of the phosphorylated forms of MAP
      kinase was observed. Again, this loss of activated MAP kinase could be prevented
      by the addition of DEVD-cho or DEVD-fmk. These data are consistent with a pathway
      whereby induction of apoptosis activates caspase-3. This enzyme then cleaves the
      regulatory Aalpha subunit of PP2A, increasing its activity. These data show that
      the activated PP2A will then effect a change in the phosphorylation state of the
      cell. These data provide a link between the caspases and signal transduction
      pathways.

PMID- 9582352
TI  - Mutational analysis of the SRC homology 2 domain protein-tyrosine phosphatase
      Corkscrew.
AB  - The SRC homology 2 (SH2) domain protein-tyrosine phosphatase, Corkscrew (CSW) is
      required for signaling by receptor tyrosine kinases, including the Sevenless
      receptor tyrosine kinase (SEV), which directs Drosophila R7 photoreceptor cell
      development. To investigate the role of the different domains of CSW, we
      constructed domain-specific csw mutations and assayed their effects on CSW
      function. Our results indicate that CSW SH2 domain function is essential, but
      either CSW SH2 domain can fulfill this requirement. We also found that CSW and
      activated SEV are associated in vivo in a manner that does not require either CSW
      SH2 domain function or tyrosine phosphorylation of SEV. In contrast, the
      interaction between CSW and Daughter of Sevenless, a CSW substrate, is dependent
      on SH2 domain function. These results suggest that the role of the CSW SH2
      domains during SEV signaling is to bind Daughter of Sevenless rather than
      activated SEV. We also found that although CSW protein-tyrosine phosphatase
      activity is required for full CSW function, a catalytically inactive CSW is
      capable of providing partial function. In addition, we found that deletion of
      either the CSW protein- tyrosine phosphatase insert or the entire CSW carboxyl
      terminus, which includes a conserved DRK/GRB2 SH2 domain binding sequence, does
      not abolish CSW function.

PMID- 9582353
TI  - Characterization of a novel cis-syn and trans-syn-II pyrimidine dimer
      glycosylase/AP lyase from a eukaryotic algal virus, Paramecium bursaria chlorella
      virus-1.
AB  - Endonuclease V from bacteriophage T4, is a cis-syn pyrimidine dimer-specific
      glycosylase. Recently, the first sequence homolog of T4 endonuclease V was
      identified from chlorella virus Paramecium bursaria chlorella virus-1 (PBCV-1).
      Here we present the biochemical characterization of the chlorella virus
      pyrimidine dimer glycosylase, cv-PDG. Interestingly, cv-PDG is specific not only
      for the cis-syn cyclobutane pyrimidine dimer, but also for the trans-syn-II
      isomer. This is the first trans-syn-II-specific glycosylase identified to date.
      Kinetic analysis demonstrates that DNAs containing both types of pyrimidine
      dimers are cleaved by the enzyme with similar catalytic efficiencies. Cleavage
      analysis and covalent trapping experiments demonstrate that the enzyme mechanism
      is consistent with the model proposed for glycosylase/AP lyase enzymes in which
      the glycosylase action is mediated via an imino intermediate between the C1' of
      the sugar and an amino group in the enzyme, followed by a beta-elimination
      reaction resulting in cleavage of the phosphodiester bond. cv-PDG exhibits
      processive cleavage kinetics which are diminished at salt concentrations greater
      than those determined for T4 endonuclease V, indicating a possibly stronger
      electrostatic attraction between enzyme and DNA. The identification of this new
      enzyme with broader pyrimidine dimer specificity raises the intriguing
      possibility that there may be other T4 endonuclease V-like enzymes with
      specificity toward other DNA photoproducts.

PMID- 9582354
TI  - New insights into the co-evolution of cytochrome c reductase and the
      mitochondrial processing peptidase.
AB  - The mitochondrial processing peptidase (MPP) is a heterodimeric enzyme that forms
      part of the cytochrome c reductase complex from higher plants. Mitochondria from
      mammals and yeast contain two homologous enzymes: (i) an active MPP within the
      mitochondrial matrix and (ii) an inactive MPP within the cytochrome c reductase
      complex. To elucidate the evolution of MPP, the cytochrome c reductase complexes
      from lower plants were isolated and tested for processing activity. Mitochondria
      were prepared from the staghorn fern Platycerium bifurcatum, from the horsetail
      Equisetum arvense, and from the colorless algae Polytomella, and cytochrome c
      reductase complexes were purified by a micro-isolation procedure based on Blue
      native polyacrylamide gel electrophoresis and electroelution. This is the first
      report on the subunit composition of a respiratory enzyme complex from a fern or
      a horsetail. The cytochrome c reductase complexes from P. bifurcatum and E.
      arvense are shown to efficiently process mitochondrial precursor proteins,
      whereas the enzyme complex from Polytomella lacks proteolytic activity. An
      evolutionary model is suggested that assumes a correlation between the presence
      of an active MPP within the cytochrome c reductase complex and the occurrence of
      chloroplasts.

PMID- 9582355
TI  - Essential role for protein kinase B (PKB) in insulin-induced glycogen synthase
      kinase 3 inactivation. Characterization of dominant-negative mutant of PKB.
AB  - Activation of phosphatidylinositide 3'-OH kinase (PI 3-kinase) is implicated in
      mediating a variety of growth factor-induced responses, among which are the
      inactivation of glycogen synthase kinase-3 (GSK-3) and the activation of the
      serine/threonine protein kinase B (PKB). GSK-3 inactivation occurs through
      phosphorylation of Ser-9, and several kinases, such as protein kinase C, mitogen
      activated protein kinase-activated protein kinase-1 (p90(Rsk)), p70(S6kinase),
      and also PKB have been shown to phosphorylate this site in vitro. In the light of
      the many candidates to mediate insulin-induced GSK-3 inactivation we have
      investigated the role of PKB by constructing a PKB mutant that exhibits dominant
      negative function (inhibition of growth factor-induced activation of PKB at
      expression levels similar to wild-type PKB), as currently no such mutant has been
      reported. We observed that the PKB mutant (PKB-CAAX) acts as an efficient
      inhibitor of PKB activation and also of insulin-induced GSK-3 regulation.
      Furthermore, it is shown that PKB and GSK-3 co-immunoprecipitate, indicating a
      direct interaction between GSK-3 and PKB. An additional functional consequence of
      this interaction is implicated by the observation that the oncogenic form of PKB,
      gagPKB induces a cellular relocalization of GSK-3 from the cytosolic to the
      membrane fraction. Our results demonstrate that PKB activation is both necessary
      and sufficient for insulin-induced GSK-3 inactivation and establish a linear
      pathway from insulin receptor to GSK-3. Regulation of GSK-3 by PKB is likely
      through direct interaction, as both proteins co-immunoprecipitate. This
      interaction also resulted in a translocation of GSK-3 to the membrane in cells
      expressing transforming gagPKB.

PMID- 9582356
TI  - ADP-ribosylation factor and Rho proteins mediate fMLP-dependent activation of
      phospholipase D in human neutrophils.
AB  - Activation of intact human neutrophils by fMLP stimulates phospholipase D (PLD)
      by an unknown signaling pathway. The small GTPase, ADP-ribosylation factor (ARF),
      and Rho proteins regulate the activity of PLD1 directly. Cell permeabilization
      with streptolysin O leads to loss of cytosolic proteins including ARF but not Rho
      proteins from the human neutrophils. PLD activation by fMLP is refractory in
      these cytosol-depleted cells. Readdition of myr-ARF1 but not non-myr-ARF1
      restores fMLP-stimulated PLD activity. C3 toxin, which inactivates Rho proteins,
      reduces the ARF-reconstituted PLD activity, illustrating that although Rho alone
      does not stimulate PLD activity, it synergizes with ARF. To identify the
      signaling pathway to ARF and Rho activation by fMLP, we used pertussis toxin and
      wortmannin to examine the requirement for heterotrimeric G proteins of the Gi
      family and for phosphoinositide 3-kinase, respectively. PLD activity in both
      intact cells and the ARF-restored response in cytosol-depleted cells is inhibited
      by pertussis toxin, indicating a requirement for Gi2/Gi3 protein. In contrast,
      wortmannin inhibited only fMLP-stimulated PLD activity in intact neutrophils, but
      it has no effect on myr-ARF1-reconstituted activity. fMLP-stimulated
      translocation of ARF and Rho proteins to membranes is not inhibited by
      wortmannin. It is concluded that activation of Gi proteins is obligatory for
      ARF/Rho activation by fMLP, but activation of phosphoinositide 3-kinase is not
      required.

PMID- 9582357
TI  - Ubiquitination of histone H3 in elongating spermatids of rat testes.
AB  - Because of the potential role of histone ubiquitination in altering chromatin
      structure, we characterized the levels of ubiquitination of specific histones in
      meiotic and postmeiotic germ cells in rat testes by two-dimensional gel
      electrophoresis. The levels of the major ubiquitinated histone forms, mono- and
      poly-ubiquitinated H2A, were highest in the pachytene spermatocyte stage,
      declined thereafter through the round spermatid stage, and reached their lowest
      levels in elongating spermatids. Three additional ubiquitinated histone species,
      besides H2A, were detected using anti-ubiquitin antibodies specifically in the
      fraction enriched in elongating spermatids. Based on their electrophoretic
      mobilities, they corresponded to uH3, uTH3, and uH2B. Polyubiquitinated forms of
      these proteins were also observed. The identity of these proteins was confirmed
      by immunoblotting with anti-H3 antisera and by differential extraction of the
      proteins from the nucleus with increasing salt concentrations. This is the first
      report of ubiquitination of H3 in vivo. We speculate that its ubiquitination
      could loosen the nucleosome structure in preparation for histone removal, be a
      consequence of nucleosome relaxation or disruption caused by other means, or
      target H3 for degradation.

PMID- 9582358
TI  - Highly mutagenic bypass synthesis by T7 RNA polymerase of site-specific
      benzo[a]pyrene diol epoxide-adducted template DNA.
AB  - We have previously developed an in vitro system that allows quantitative
      evaluation of the fidelity of transcription during synthesis on a natural
      template in the presence of all four nucleotides. Here, we have employed this
      system using a TAA ochre codon reversion assay to examine the fidelity of
      transcription by T7 RNA polymerase past an adenine residue adducted at the N6
      position with (-)-anti-trans- or (+)-anti-trans-benzo[a]pyrene diol epoxide
      (BPDE). T7 RNAP was capable of transcribing past either BPDE isomer to generate
      full-length run-off transcripts. The extent of bypass was found to be 32% for the
      (-)-anti-trans-isomer and 18% for the (+)-anti-trans-isomer. Transcription past
      both adducts was highly mutagenic. The reversion frequency of bypass synthesis of
      the (-)-anti-trans-isomer was elevated 11,000-fold and that of the (+)-anti-trans
      isomer 6000-fold, relative to the reversion frequency of transcription on
      unadducted template. Adenine was misinserted preferentially, followed by guanine,
      opposite the adenine adducted with either BPDE isomer. Although base substitution
      errors were by far the most frequent mutation on the adducted template, three-
      and six-base deletions were also observed. These results suggest that
      transcriptional errors, particularly with regard to damage bypass, may contribute
      to the mutational burden of the cell.

PMID- 9582359
TI  - Multiple binding sites in the interaction between an extracellular fibrinogen
      binding protein from Staphylococcus aureus and fibrinogen.
AB  - Efb (previously Fib) is a fibrinogen-binding protein secreted by Staphylococcus
      aureus. It has previously been shown that it plays a role in a wound infection
      model in the rat and that antibodies against Efb reduce the number of recovered
      bacteria from the mammary glands in a mouse mastitis model. Efb binds to the
      alpha-chain of fibrinogen and does not participate in bacterial adherence to
      fibrinogen. The binding of Efb to fibrinogen is divalent, with one binding site
      within the two repeat regions in Efb at the N terminus and one binding site at
      the C terminus. The divalent binding nature leads to precipitation of Efb
      fibrinogen complex when the proteins are added to each other at a 1:1 molar
      ratio. The interaction between Efb and fibrinogen is strongly enhanced by Ca2+ or
      Zn2+ but not by Mg2.

PMID- 9582361
TI  - A genetic screen for aminophospholipid transport mutants identifies the
      phosphatidylinositol 4-kinase, STT4p, as an essential component in
      phosphatidylserine metabolism.
AB  - In an effort to understand molecular mechanisms of intracellular lipid transport,
      we have focused upon specific events required for de novo aminophospholipid
      synthesis in the yeast Saccharomyces cerevisiae. A genetic system for examining
      the steps between phosphatidylserine (PtdSer) synthesis in the endoplasmic
      reticulum and its transport to and decarboxylation by PtdSer decarboxylase 2 in
      the Golgi/vacuole has been developed. We have isolated a mutant, denoted pstB1,
      that accumulates PtdSer and has diminished phosphatidylethanolamine formation
      despite normal PtdSer decarboxylase 2 activity. The lesion in PtdSer metabolism
      is consistent with a defect in interorganelle lipid transport. A genomic DNA
      clone that complements the mutation was isolated, and sequencing revealed that
      the clone contains the STT4 gene, encoding a phosphatidylinositol 4-kinase. The
      pstB1 mutant exhibits a defect in Stt4p-type phosphatidylinositol 4-kinase
      activity, and direct gene replacement indicates that STT4 is the defective gene
      in the mutant. Creation of an STT4 null allele (stt4Delta::HIS3) demonstrates the
      gene is essential. These results provide evidence that implicates
      phosphoinositides in the regulation of intracellular aminophospholipid transport.

PMID- 9582360
TI  - Substrate specificity of delta ribozyme cleavage.
AB  - The specificity of delta ribozyme cleavage was investigated using a trans-acting
      antigenomic delta ribozyme. Under single turnover conditions, the wild type
      ribozyme cleaved the 11-mer ribonucleotide substrate with a rate constant of 0.34
      min-1, an apparent Km of 17.9 nM and an apparent second-order rate constant of
      1.89 x 10(7) min-1 M-1. The substrate specificity of the delta ribozyme was
      thoroughly investigated using a collection of substrates that varied in either
      the length or the nucleotide sequence of their P1 stems. We observed that not
      only is the base pairing of the substrate and the ribozyme important to cleavage
      activity, but also both the identity and the combination of the nucleotide
      sequence in the substrates are essential for cleavage activity. We show that the
      nucleotides in the middle of the P1 stem are essential for substrate binding and
      subsequent steps in the cleavage pathway. The introduction of any mismatches at
      these positions resulted in a complete lack of cleavage by the wild type
      ribozyme. Our findings suggest that factors more complex than simple base pairing
      interactions, such as tertiary structure interactions, could play an important
      role in the substrate specificity of delta ribozyme cleavage.

PMID- 9582362
TI  - In NIH-3T3 fibroblasts, insulin receptor interaction with specific protein kinase
      C isoforms controls receptor intracellular routing.
AB  - Insulin increased protein kinase C (PKC) activity by 2-fold in both membrane
      preparations and insulin receptor (IR) antibody precipitates from NIH-3T3 cells
      expressing human IRs (3T3hIR). PKC-alpha, -delta, and -zeta were barely
      detectable in IR antibody precipitates of unstimulated cells, while increasing by
      7-, 3.5-, and 3-fold, respectively, after insulin addition. Preexposure of 3T3hIR
      cells to staurosporine reduced insulin-induced receptor coprecipitation with PKC
      alpha, -delta, and -zeta by 3-, 4-, and 10-fold, respectively, accompanied by a
      1.5-fold decrease in insulin degradation and a similar increase in insulin
      retroendocytosis. Selective depletion of cellular PKC-alpha and -delta, by 24 h
      of 12-O-tetradecanoylphorbol-13-acetate (TPA) exposure, reduced insulin
      degradation by 3-fold and similarly increased insulin retroendocytosis, with no
      change in PKC-zeta. In lysates of NIH-3T3 cells expressing the R1152Q/K1153A IRs
      (3T3Mut), insulin-induced coprecipitation of PKC-alpha, -delta, and -zeta with
      the IR was reduced by 10-, 7-, and 3-fold, respectively. Similar to the 3T3hIR
      cells chronically exposed to TPA, untreated 3T3Mut featured a 3-fold decrease in
      insulin degradation, with a 3-fold increase in intact insulin retroendocytosis.
      Thus, in NIH-3T3 cells, insulin elicits receptor interaction with multiple PKC
      isoforms. Interaction of PKC-alpha and/or -delta with the IR appears to control
      its intracellular routing.

PMID- 9582363
TI  - Specific inhibition of in vitro formation of protease-resistant prion protein by
      synthetic peptides.
AB  - The transmissible spongiform encephalopathies are characterized by the conversion
      of the protease-sensitive prion protein (PrPsen) into a protease-resistant
      isoform (PrPres) associated with the neuropathogenic process in vivo. Recently,
      PrPres has been shown to be capable of directly inducing the conversion of PrPsen
      to PrPres in a cell-free in vitro system. In the present experiments, various PrP
      peptides were studied for their ability to enhance or inhibit this cell-free
      conversion reaction. None of the synthetic peptides was able to confer protease
      resistance to the labeled PrPsen molecules on their own. On the contrary,
      peptides from the central part of the hamster PrP sequence from 106 to 141 could
      completely inhibit the conversion induced by preformed PrPres. The presence of
      residues 119 and 120 from the highly hydrophobic sequence AGAAAAGA (position 113
      to 120) was crucial for an efficient inhibitory effect. Fourier transform
      infrared spectroscopy analysis indicated that inhibitory peptides formed high
      beta-sheet aggregates under the conditions of the conversion reaction, but this
      was also true of certain peptides that were not inhibitory. Thus, the potential
      to form beta-sheeted aggregates may be necessary, but not sufficient, for
      peptides to act as inhibitors of PrPres formation. Clearly, the amino acid
      sequence of the peptide is also important for inhibition. The sequence
      specificity of the inhibition is consistent with the idea that residues in the
      vicinity of positions 106-141 of PrPres and/or PrPsen are critically involved in
      the intermolecular interactions that lead to PrPres formation.

PMID- 9582364
TI  - Role of Sp proteins and RORalpha in transcription regulation of murine
      prosaposin.
AB  - Prosaposin is the precursor of four low molecular weight sphingolipid-activating
      proteins (SAPs) or saposins. These four proteins function as intracellular
      activators of several lysosomal enzymes involved in the degradation of
      glycosphingolipids, and prosaposin itself has neurite outgrowth effects.
      Expression of prosaposin is regulated in a temporal and spatial manner with
      expression in specific brain neurons and visceral cell types. Here a major
      regulatory fragment was characterized within 310 bp 5' to the transcription start
      site. Using electrophoretic mobility shift assay (EMSA) and DNA footprinting,
      members of the Sp family (Sp1, Sp3, and Sp4), the orphan nuclear receptor
      (RORalpha), and an unknown transcription factor (U; TGGGGGAG) were shown to bind
      to this region. To evaluate the role of such transcription factor binding sites
      for this locus, a series of mutant constructs was generated within this region,
      and their function was evaluated in cultured NS20Y neuroblastoma cells. A 3' Sp1
      site, a 5' Sp1/U cluster and the RORalpha binding sites were functional. The data
      are consistent with a model in which the factors that bind to the Sp1/U cluster
      and RORE site interact negatively to diminish promoter activity to a background
      level that is determined primarily by the 3' Sp1 site. These interactions depend
      on the tissue-specific repertoire of transcription factors leading to
      differential expression of this locus.

PMID- 9582365
TI  - Sequence requirements for association of protein-tyrosine phosphatase PEP with
      the Src homology 3 domain of inhibitory tyrosine protein kinase p50(csk).
AB  - Previously, we reported that the inhibitory tyrosine protein kinase p50(csk) is
      physically associated with the protein-tyrosine phosphatase PEP in hematopoietic
      cells. This interaction was shown to involve the Src homology 3 (SH3) region of
      Csk and a proline-rich sequence of PEP termed P1 (SRRTDDEIPPPLPERTPESFIVVEE). In
      this report, we have attempted to understand the structural basis for the highly
      specific association of these two molecules in vivo. Our studies revealed that
      the proline-rich core of the P1 region of PEP (PPPLPERT) was necessary but not
      sufficient for binding to p50(csk). Additional sequences located carboxyl to this
      motif were also needed for binding to the Csk SH3 domain in vitro and in vivo.
      Further analyses revealed that two aliphatic residues (isoleucine 625 and valine
      626; PESFIVVEE) were especially important for this effect. In addition to
      clarifying the molecular basis for the selective ability of PEP to associate with
      Csk, these results constitute further evidence that sequences outside proline
      rich cores dictate the specificity of SH3 domain-mediated interactions in vivo.

PMID- 9582366
TI  - Integrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP
      2. Roles of Fak and Src family kinases.
AB  - SHPS-1 is a receptor-like glycoprotein that undergoes tyrosine phosphorylation
      and binds SHP-2, an Src homology 2 domain containing protein tyrosine
      phosphatase, in response to various mitogens. Cell adhesion to extracellular
      matrix proteins such as fibronectin and laminin also induced the tyrosine
      phosphorylation of SHPS-1 and its association with SHP-2. These responses were
      markedly reduced in cells overexpressing the Csk kinase or in cells that lack
      focal adhesion kinase or the Src family kinases Src or Fyn. However, unlike Src,
      focal adhesion kinase did not catalyze phosphorylation of the cytoplasmic domain
      of SHPS-1 in vitro. Overexpression of a catalytically inactive SHP-2 markedly
      inhibited activation of mitogen-activated protein (MAP) kinase in response to
      fibronectin stimulation without affecting the extent of tyrosine phosphorylation
      of focal adhesion kinase or its interaction with the docking protein Grb2.
      Overexpression of wild-type SHPS-1 did not enhance fibronectin-induced activation
      of MAP kinase. These results indicate that the binding of integrins to the
      extracellular matrix induces tyrosine phosphorylation of SHPS-1 and its
      association with SHP-2, and that such phosphorylation of SHPS-1 requires both
      focal adhesion kinase and an Src family kinase. In addition to its role in
      receptor tyrosine kinase-mediated MAP kinase activation, SHP-2 may play an
      important role, partly through its interaction with SHPS-1, in the activation of
      MAP kinase in response to the engagement of integrins by the extracellular
      matrix.

PMID- 9582367
TI  - Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals
      functional similarities with keratinocyte growth factor (FGF-7).
AB  - A newly identified member of the fibroblast growth factor (FGF) family,
      designated FGF-10, is expressed during development and preferentially in adult
      lung. The predicted FGF-10 protein is most related to keratinocyte growth factor
      (KGF, or FGF-7). The latter is unique among FGFs in that it binds and signals
      only through the FGF receptor (FGFR2b) isoform KGF receptor (KGFR) expressed
      specifically by epithelial cells. In order to examine the biological and
      biochemical properties of human FGF-10, we isolated the cDNA and expressed its
      encoded protein in bacteria. The recombinant protein (rFGF-10) was a potent
      mitogen for Balb/MK mouse epidermal keratinocytes with activity detectable at 0.1
      nM and maximal at around 5 nM. Within this concentration range, FGF-10 did not
      stimulate DNA synthesis in NIH/3T3 mouse fibroblasts. rFGF-10 bound the KGFR with
      high affinity comparable to that of KGF, and did not bind detectably to either
      the FGFR1c (Flg) or FGFR2c (Bek) receptor isoforms. The mitogenic activity of FGF
      10 could be distinguished from that of KGF by its different sensitivity to
      heparin and lack of neutralization by a KGF monoclonal antibody. These results
      indicate that FGF-10 and KGF have similar receptor binding properties and target
      cell specificities, but are differentially regulated by components of the
      extracellular matrix.

PMID- 9582368
TI  - In vivo expression of an alternatively spliced human tumor message that encodes a
      truncated form of cathepsin B. Subcellular distribution of the truncated enzyme
      in COS cells.
AB  - Cathepsin B is a lysosomal cysteine protease whose increased expression is
      believed to be linked to the malignant progression of tumors. Alternative
      splicing and the use of alternative transcription initiation sites in humans
      produce cathepsin B mRNAs that differ in their 5'- and 3'-untranslated ends. Some
      human tumors also contain cathepsin B-related transcripts that lack exon 3 which
      encodes the N-terminal signal peptide and 34 of the 62-amino acid inhibitory
      propeptide. In this study we show that one such transcript, CB(-2,3), which is
      missing exons 2 and 3, is likely to be a functional message in tumors. Thus, CB(
      2,3) was found to be otherwise complete, containing the remainder of the
      cathepsin B coding sequence and the part of the 3'-untranslated region that is
      common to all previously characterized cathepsin B mRNAs in humans. Its in vitro
      translation product can be folded to produce enzymatic activity against the
      cathepsin B-specific substrate, Nalpha-benzyloxycarbonyl-L-Arg-L-Arg-4
      methylcoumaryl-7-amide. Endogenous CB(-2,3) from the metastatic human melanoma
      cell line, A375M, co-sediments with polysomes, indicating that it engages the
      eukaryotic translation machinery in these cells. Epitope-tagged forms of the
      truncated cathepsin B from CB(-2,3) are produced in amounts comparable to the
      normal protein after transient transfection into COS cells. Immunofluorescence
      microscopy and subcellular fractionation show this novel tumor form of cathepsin
      B to be associated with nuclei and other membranous organelles, where it is
      likely to be bound to the cytoplasmic face of the membranes. This subcellular
      distribution was different from the lysosomal pattern shown by the epitope
      tagged, full-length cathepsin B in COS cells. These results indicate that the
      message missing exons 2 and 3 is likely to be translated into a catalytically
      active enzyme, and that alternative splicing (exon skipping) could contribute to
      the aberrant intracellular trafficking of cathepsin B that is observed in some
      human cancers.

PMID- 9582369
TI  - Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor
      induced apoptosis and activation of nuclear transcription factor-kappaB and
      activated protein-1.
AB  - Several recently identified intracellular proteins associate with the tumor
      necrosis factor (TNF) receptor and activate nuclear transcription factor (NF)
      kappaB, c-Jun kinase, and apoptosis. However, the mechanism is not understood. In
      the present report, we investigated the role of reactive oxygen intermediates in
      TNF-induced signaling. Overexpression of manganese superoxide dismutase (Mn-SOD)
      in human breast cancer MCF-7 cells completely abolished TNF-mediated NF-kappaB
      activation, IkappaB alpha degradation, p65 nuclear translocation, and NF-kappaB
      dependent reporter gene expression. Besides TNF, phorbol ester-, okadaic acid-,
      ceramide-, and lipopolysaccharide-induced activation of NF-kappaB was blocked by
      Mn-SOD, indicating a common pathway of activation. H2O2-induced NF-kappaB
      activation, however, was potentiated. In addition, Mn-SOD blocked the TNF
      mediated activation of activated protein-1, stress-activated c-Jun protein
      kinase, and mitogen-activated protein kinase kinase. TNF-induced
      antiproliferative effects and caspase-3 activation, indicators of apoptosis, were
      also completely suppressed by transfection of cells with Mn-SOD. Suppression of
      apoptosis induced by okadaic acid, H2O2, and taxol was also inhibited by Mn-SOD
      but not that induced by vincristine, vinblastine, or daunomycin. Overall, these
      results demonstrate that, in addition to several recently identified signaling
      molecules, reactive oxygen intermediates play a critical role in activation of NF
      kappaB, activated protein-1, c-Jun kinase, and apoptosis induced by TNF and other
      agents.

PMID- 9582370
TI  - Rrp6p, the yeast homologue of the human PM-Scl 100-kDa autoantigen, is essential
      for efficient 5.8 S rRNA 3' end formation.
AB  - The eukaryotic 25 S, 18 S, and 5.8 S rRNAs are synthesized as a single transcript
      with two internal transcribed spacers (ITS1 and ITS2), which are removed by endo-
      and exoribonucleolytic steps to produce mature rRNA. Genetic selection for
      suppressors of a polyadenylation defect yielded two cold-sensitive alleles of a
      gene that we named RRP6 (ribosomal RNA processing). Molecular cloning of RRP6
      revealed its homology to a 100-kDa human, nucleolar PM-Scl autoantigen and to
      Escherichia coli RNase D, a 3'-5' exoribonuclease. Recessive mutations in rrp6
      result in the accumulation of a novel 5. 8 S rRNA processing intermediate, called
      5.8 S*, which has normal 5' ends, but retains approximately 30 nucleotides of
      ITS2. Pulse-chase analysis of 5.8 S rRNA processing in an rrp6- strain revealed a
      precursor-product relationship between 5.8 S* and 5.8 S rRNAs, suggesting that
      Rrp6p plays a role in the removal of the last 30 nucleotides of ITS2 from 5.8 S
      precursors. A portion of 5.8 S* rRNA assembles into 60 S ribosomes which form
      polyribosomes, suggesting that they function in protein synthesis. These findings
      indicate that Rrp6p plays a role in 5.8 S rRNA 3' end formation, and they
      identify a functional intermediate in the rRNA processing pathway.

PMID- 9582371
TI  - Assembly of iron-sulfur clusters. Identification of an iscSUA-hscBA-fdx gene
      cluster from Azotobacter vinelandii.
AB  - An enzyme having the same L-cysteine desulfurization activity previously
      described for the NifS protein was purified from a strain of Azotobacter
      vinelandii deleted for the nifS gene. This protein was designated IscS to
      indicate its proposed role in iron-sulfur cluster assembly. Like NifS, IscS is a
      pyridoxal-phosphate containing homodimer. Information gained from microsequencing
      of oligopeptides obtained by tryptic digestion of purified IscS was used to
      design a strategy for isolation and DNA sequence analysis of a 7,886-base pair A.
      vinelandii genomic segment that includes the iscS gene. The iscS gene is
      contained within a gene cluster that includes homologs to nifU and another gene
      contained within the major nif cluster of A. vinelandii previously designated
      orf6. These genes have been designated iscU and iscA, respectively. Information
      available from complete genome sequences of Escherichia coli and Hemophilus
      influenzae reveals that they also encode iscSUA gene clusters. A wide
      conservation of iscSUA genes in nature and evidence that NifU and NifS
      participate in the mobilization of iron and sulfur for nitrogenase-specific iron
      sulfur cluster formation suggest that the products of the iscSUA genes could play
      a general role in the formation or repair of iron-sulfur clusters. The proposal
      that IscS is involved in mobilization of sulfur for iron-sulfur cluster formation
      in A. vinelandii is supported by the presence of a cysE-like homolog in another
      gene cluster located immediately upstream from the one containing the iscSUA
      genes. O-Acetylserine synthase is the product of the cysE gene, and it catalyzes
      the rate-limiting step in cysteine biosynthesis. A similar cysE-like gene is also
      located within the nif gene cluster of A. vinelandii. The likely role of such
      cysE-like gene products is to increase the cysteine pool needed for iron-sulfur
      cluster formation. Another feature of the iscSUA gene cluster region from A.
      vinelandii is that E. coli genes previously designated as hscB, hscA, and fdx are
      located immediately downstream from, and are probably co-transcribed with, the
      iscSUA genes. The hscB, hscA, and fdx genes are also located adjacent to the
      iscSUA genes in both E. coli and H. influenzae. The E. coli hscA and hscB gene
      products have previously been shown to bear primary sequence identity when
      respectively compared with the dnaK and dnaJ gene products and have been proposed
      to be members of a heat-shock-cognate molecular chaperone system of unknown
      function. The close proximity and apparent co-expression of iscSUA and hscBA in
      A. vinelandii indicate that the proposed chaperone function of the hscBA gene
      products could be related to the maturation of iron-sulfur cluster-containing
      proteins. Attempts to place non-polar insertion mutations within either A.
      vinelandii iscS or hscA revealed that such mutations could not be stably
      maintained in the absence of the corresponding wild-type allele. These results
      reveal a very strong selective pressure against the maintenance of A. vinelandii
      iscS or hscA knock-out mutations and suggest that such mutations are either
      lethal or highly deleterious. In contrast to iscS or hscA, a strain having a
      polar insertion mutation within the cysE-like gene was readily isolated and could
      be stably maintained. These results show that the cysE-like gene located upstream
      from iscS is not essential for cell growth and that the cysE-like gene and the
      iscSUA-hscBA-fdx genes are contained within separate transcription units.

PMID- 9582372
TI  - A conserved C-terminal domain in PBX increases DNA binding by the PBX homeodomain
      and is not a primary site of contact for the YPWM motif of HOXA1.
AB  - HOX proteins are dependent upon cofactors of the PBX family for specificity of
      DNA binding. Two regions that have been implicated in HOX/PBX cooperative
      interactions are the YPWM motif, found N-terminal to the HOX homeodomain, and the
      GKFQ domain (also known as the Hox cooperativity motif) immediately C-terminal to
      the PBX homeodomain. Using derivatives of the E2A-PBX oncoprotein, we find that
      the GKFQ domain is not essential for cooperative interaction with HOXA1 but
      contributes to the stability of the complex. By contrast, the YPWM motif is
      strictly required for cooperative interactions in vitro and in vivo, even with
      mutants of E2A-PBX lacking the GKFQ domain. Using truncated PBX proteins, we show
      that the YPWM motif contacts the PBX homeodomain. The presence of the GKFQ domain
      increases monomer binding by the PBX homeodomain 5-fold, and the stability of the
      HOXA1.E2A-PBX complex 2-fold. These data suggest that the GKFQ domain acts mainly
      to increase DNA binding by PBX, rather than providing a primary contact site for
      the YPWM motif of HOXA1. We have identified 2 residues, Glu-301 and Tyr-305,
      required for GKFQ function and suggest that this is dependent on alpha-helical
      character.

PMID- 9582373
TI  - An analysis of Mek1 signaling in cell proliferation and transformation.
AB  - The Mek1 dual specificity protein kinase phosphorylates and activates the mitogen
      activated protein kinases Erk1 and Erk2 in response to mitogenic stimulation. The
      molecular events downstream of Mek and Erk necessary to promote cell cycle entry
      are largely undefined. In order to study signals emanating from Mek independent
      of upstream proteins capable of activating multiple signaling pathways, we fused
      the hormone-binding domain of the estrogen receptor (ER) to the C terminus of
      constitutively activated Mek1 phosphorylation site mutants. Although 4-OH
      tamoxifen stimulation of NIH-3T3 cells expressing constitutively activated Mek-ER
      resulted in only a small increase in specific activity of the fusion protein, a 5
      10 fold increase in total cellular Mek activity was observed over a period of 1-2
      days due to an accumulation of fusion protein. Induction of constitutively
      activated Mek-ER in NIH-3T3 cells resulted in accelerated S phase entry,
      proliferation in low serum, morphological transformation, and anchorage
      independent growth. Endogenous Erk1 and Erk2 were phosphorylated with kinetics
      similar to the elevation of Mek-ER activity. However, elevated Mek-ER activity
      attenuated subsequent stimulation of Erk1 and Erk2 by serum. 4-OH-tamoxifen
      stimulation of Mek-ER-expressing fibroblasts also resulted in up-regulation of
      cyclin D1 expression and down-regulation of p27(Kip1) expression, establishing a
      direct link between Mek1 and the cell cycle machinery.

PMID- 9582374
TI  - Guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) stimulation of GLUT4
      translocation is tyrosine kinase-dependent.
AB  - Guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) treatment of permeabilized
      adipocytes results in GLUT4 translocation similar to that elicited by insulin
      treatment. However, although the selective phosphatidylinositol 3-kinase
      inhibitor, wortmannin, completely prevented insulin-stimulated GLUT4
      translocation, it was without effect on GTPgammaS-stimulated GLUT4 translocation.
      In addition, insulin was an effective stimulant, whereas GTPgammaS was a very
      weak activator of the downstream Akt serine/threonine kinase. Consistent with an
      Akt-independent mechanism, guanosine 5'-O-2-(thio)diphosphate inhibited insulin
      stimulated GLUT4 translocation without any effect on the Akt kinase.
      Surprisingly, two functionally distinct tyrosine kinase inhibitors, genistein and
      herbimycin A, as well as microinjection of a monoclonal phosphotyrosine specific
      antibody, inhibited both GTPgammaS- and insulin-stimulated GLUT4 translocation.
      Phosphotyrosine immunoblotting and specific immunoprecipitation demonstrated that
      GTPgammaS did not elicit tyrosine phosphorylation of insulin receptor or insulin
      receptor substrate-1. In contrast to insulin, proteins in the 120-130-kDa and 55
      75-kDa range were tyrosine-phosphorylated following GTPgammaS stimulation.
      Several of these proteins were identified and include protein-tyrosine kinase 2
      (also known as CAKbeta, RAFTK, and CADTK), pp125 focal adhesion tyrosine kinase,
      pp130 Crk-associated substrate, paxillin, and Cbl. These data demonstrate that
      the GTPgammaS-stimulated GLUT4 translocation utilizes a novel tyrosine kinase
      pathway that is independent of both the phosphatidylinositol 3-kinase and the Akt
      kinase.

PMID- 9582375
TI  - The HOXC11 homeodomain protein interacts with the lactase-phlorizin hydrolase
      promoter and stimulates HNF1alpha-dependent transcription.
AB  - The lactase-phlorizin hydrolase (LPH) gene is expressed specifically in the
      enterocytes of the small intestine. LPH levels are high in newborn mammals, but
      decrease after weaning. We have previously suggested that the promoter element CE
      LPH1, located at -40 to -54, plays an important role in this down-regulation,
      because the DNA binding activity of a nuclear factor that binds to this site is
      present specifically in small intestinal extracts and is down-regulated after
      weaning. In an effort to clone CE-LPH1-binding factors, a yeast one-hybrid
      genetic selection was used, resulting in the isolation of a partial cDNA encoding
      the human homeodomain protein HOXC11. The full-length HOXC11 sequence was
      obtained by rapid amplification of cDNA ends. It was shown in a yeast assay and
      by electrophoretic mobility shift assay that HOXC11 binds to the CE-LPH1 element
      with similar specificity to the endogenous intestinal factor. Two HOXC11
      transcript sizes were identified by Northern blot analysis. The larger transcript
      (2.1 kilobase pairs) is likely to contain a translational start site in good
      context and is present in HeLa cells. The shorter 1.7-kilobase pair transcript,
      present in HeLa and Caco-2 cells, probably encodes a protein lacking 114 amino
      acids at the N-terminal end. Both forms of HOXC11 potentiate transcriptional
      activation of the LPH promoter by HNF1alpha. The expression of HOXC11 mRNA in
      human fetal intestine suggests a role in early intestinal development.

PMID- 9582376
TI  - Ada protein-RNA polymerase sigma subunit interaction and alpha subunit-promoter
      DNA interaction are necessary at different steps in transcription initiation at
      the Escherichia coli Ada and aidB promoters.
AB  - The methylated form of the Ada protein (meAda) binds the ada and aidB promoters
      between 60 and 40 base pairs upstream from the transcription start and activates
      transcription of the Escherichia coli ada and aidB genes. This region is also a
      binding site for the alpha subunit of RNA polymerase and resembles the rrnB P1 UP
      element in A/T content and location relative to the core promoter. In this
      report, we show that deletion of the C-terminal domain of the alpha subunit
      severely decreases meAda-independent binding of RNA polymerase to ada and aidB,
      affecting transcription initiation at these promoters. We provide evidence that
      meAda activates transcription by direct interaction with the C-terminal domain of
      RNA polymerase sigma70 subunit (amino acids 574-613). Several negatively charged
      residues in the sigma70 C-terminal domain are important for transcription
      activation by meAda; in particular, a glutamic acid to valine substitution at
      position 575 has a dramatic effect on meAda-dependent transcription. Based on
      these observations, we propose that the role of the alpha subunit at ada and aidB
      is to allow initial binding of RNA polymerase to the promoters. However,
      transcription initiation is dependent on meAda-sigma70 interaction.

PMID- 9582377
TI  - Vascular endothelial growth factor induces expression of the antiapoptotic
      proteins Bcl-2 and A1 in vascular endothelial cells.
AB  - We examined the role of vascular endothelial growth factor (VEGF) in preventing
      apoptosis in primary human umbilical vein endothelial (HUVE) cells. VEGF was
      capable of preventing serum starvation-induced apoptosis at concentrations
      between 10 and 100 ng/ml. The addition of VEGF to serum-starved HUVE cells led to
      a 5. 2-fold induction of Bcl-2 after 36 h and to a transient, 2.4-fold induction
      of A1 after a 7-h incubation, as quantitated by real time reverse transcriptase
      polymerase chain reaction analysis. Western blot analysis demonstrated a 2-3-fold
      induction of Bcl-2 protein after 18-36 h of exposure to VEGF and a transient
      induction of A1 after 7 h of VEGF stimulation. Moreover, overexpression of Bcl-2
      by means of transient biolistic transfection experiments of HUVE cells was
      sufficient to prevent endothelial cells from apoptotic cell death in the absence
      of VEGF. These findings indicate that Bcl-2 plays an important role in mediating
      the survival activity of VEGF on endothelial cells.

PMID- 9582378
TI  - Estradiol-induced phosphorylation of serine 118 in the estrogen receptor is
      independent of p42/p44 mitogen-activated protein kinase.
AB  - Phosphorylation of Ser118 of human estrogen receptor alpha (ER) enhances ER
      mediated transcription and is induced by hormone binding and by activation of the
      mitogen-activated protein kinase (MAPK) pathway. We discovered that
      phosphorylation of Ser118 reduces the electrophoretic mobility of the ER. Using
      this mobility shift as an assay, we determined the in vivo stoichiometry and
      kinetics of Ser118 phosphorylation in response to estradiol, ICI 182,780,
      epidermal growth factor (EGF), and phorbol 12-myristate 13-acetate (PMA). In
      human breast cancer MCF-7 cells, estradiol induced a steady state phosphorylation
      of Ser118 within 20 min with a stoichiometry of 0.67 mol of phosphate/mol of ER.
      Estradiol did not activate p42/p44 MAPK, and basal p42/p44 MAPK activity was not
      sufficient to account for phosphorylation of Ser118 in response to estradiol. In
      contrast, both EGF and PMA induced a rapid, transient phosphorylation of Ser118
      with a stoichiometry of approximately 0. 25, and the onset of Ser118
      phosphorylation correlated with the onset of p42/p44 MAPK activation by these
      agents. Either the EGF- or PMA-induced Ser118 phosphorylation could be inhibited
      without influencing estradiol-induced Ser118 phosphorylation. The data suggest
      that a kinase other than p42/p44 MAPK is involved in the estradiol-induced Ser118
      phosphorylation. We propose that the hormone-induced change in ER conformation
      exposes Ser118 for phosphorylation by a constitutively active kinase.

PMID- 9582379
TI  - The microheterogeneity of the mammalian H1(0) histone. Evidence for an age
      dependent deamidation.
AB  - Histone H1(0) is known to consist of two subfractions named H1(0)a and H1(0)b.
      The present work was performed with the aim of elucidating the nature of these
      two subfractions. By using reversed-phase high performance liquid chromatography
      in combination with hydrophilic interaction liquid chromatography, we
      fractionated human histone H1(0) into even four subfractions. Hydrophilic
      interaction liquid chromatographic analysis of the peptide fragments obtained
      after cleavage with cyanogen bromide and digestion with chymotrypsin suggested
      that the four H1(0) subfractions differ only in their small N-terminal end of the
      H1(0) molecule (30 residues). Edman degradation of the N-terminal H1(0) peptide
      fragments and mass spectra analysis have indicated that human histone H1(0)
      consists of intact histones H1(0) (named H1(0) Asn-3) and deamidated H1(0) forms
      (H1(0) Asp-3) having an aspartic acid residue at position 3 instead of
      asparagine. Moreover, both H1(0) Asn-3 and H1(0) Asp-3 are blocked (H1(0)a Asn-3,
      H1(0)a Asp-3) and unblocked (H1(0)b Asn-3, H1(0)b Asp-3) on their N terminus.
      Acid-urea gel electrophoretic analysis has shown that the histone subfraction, in
      the literature originally named H1(0)a, actually consists of a mixture of H1(0)a
      Asn-3 and H1(0)a Asp-3, whereas H1(0)b consists of H1(0)b Asn-3 and H1(0)b Asp-3.
      Furthermore, we found that hydrophilic interaction liquid chromatography
      separates rat and mouse histone H1(0) just like human H1(0) into four
      subfractions. Hydrophilic interaction liquid chromatographic analysis of brain
      and liver histone H1(0) from rats of different ages revealed an age-dependent
      increase of both the N-terminally acetylated and the deamidated forms of H1(0).
      In addition, we found that the relative proportions of the four forms of H1(0)
      histones differ from tissue to tissue.

PMID- 9582380
TI  - Oxidative stress inhibits calpain activity in situ.
AB  - In this study, the effects of oxidative stress on calpain-mediated proteolysis
      and calpain I autolysis in situ were examined. Calpain activity was stimulated in
      SH-SY5Y human neuroblastoma cells with the calcium ionophore, ionomycin. Calpain
      mediated proteolysis of the membrane-permeable fluorescent substrate N-succinyl-L
      leucyl-L-leucyl-L-valyl-L-tyrosine-7-amido-4-methylcouma rin, as well as the
      endogenous protein substrates microtubule-associated protein 2, tau and spectrin,
      was measured. Oxidative stress, induced by addition of either doxorubicin or 2
      mercaptopyridine N-oxide, resulted in a significant decrease in the extent of
      ionophore-stimulated calpain activity of both the fluorescent compound and the
      endogenous substrates compared with control, normoxic conditions. Addition of
      glutathione ethyl ester, as well as other antioxidants, resulted in the
      retention/recovery of calpain activity, indicating that oxidation-induced calpain
      inactivation was preventable/reversible. The rate of autolytic conversion of the
      large subunit of calpain I from 80 to 78 to 76 kDa was decreased during oxidative
      stress; however, the extent of calpain autolysis was not altered. These data
      indicate that oxidative stress may reversibly inactivate calpain I in vivo.

PMID- 9582381
TI  - Localization of the binding site for transforming growth factor-beta in human
      alpha2-macroglobulin to a 20-kDa peptide that also contains the bait region.
AB  - alpha2-Macroglobulin (alpha2M) functions as a major carrier of transforming
      growth factor-beta (TGF-beta) in vivo. The goal of this investigation was to
      characterize the TGF-beta-binding site in alpha2M. Human alpha2M, which was
      reduced and denatured to generate 180-kDa subunits, bound TGF-beta1, TGF-beta2,
      and NGF-beta in ligand blotting experiments. Cytokine binding was not detected
      with bovine serum albumin that had been reduced and alkylated, and only minimal
      binding was detected with purified murinoglobulin. To localize the TGF-beta
      binding site in alpha2M, five cDNA fragments, collectively encoding amino acids
      122-1302, were expressed as glutathione S-transferase (GST) fusion proteins. In
      ligand blotting experiments, TGF-beta2 bound only to the fusion protein (FP3)
      that includes amino acids 614-797. FP3 bound 125I-TGF-beta1 and 125I-TGF-beta2 in
      solution, preventing the binding of these growth factors to immobilized alpha2M
      methylamine (alpha2M-MA). The IC50 values were 33 +/- 5 and 26 +/- 6 nM for TGF
      beta1 and TGF-beta2, respectively; these values were comparable with or lower
      than those determined with native alpha2M or alpha2M-MA. A GST fusion protein
      that includes amino acids 798-1082 of alpha2M (FP4) and purified GST did not
      inhibit the binding of TGF-beta to immobilized alpha2M-MA. FP3 (0.2 microM)
      neutralized the activity of TGF-beta1 and TGF-beta2 in fetal bovine heart
      endothelial (FBHE) cell proliferation assays; FP4 was inactive in this assay. FP3
      also increased NO synthesis by RAW 264.7 cells, mimicking an alpha2M activity
      that has been attributed to the neutralization of endogenously synthesized TGF
      beta. Thus, we have isolated a peptide corresponding to 13% of the alpha2M
      sequence that binds TGF-beta and neutralizes the activity of TGF-beta in two
      separate biological assays.

PMID- 9582382
TI  - Viral protein R regulates docking of the HIV-1 preintegration complex to the
      nuclear pore complex.
AB  - Replication of human immunodeficiency virus type 1 (HIV-1) in non-dividing cells
      depends critically on import of the viral preintegration complex into the
      nucleus. Recent evidence suggests that viral protein R (Vpr) plays a key
      regulatory role in this process by binding to karyopherin alpha, a cellular
      receptor for nuclear localization signals, and increasing its affinity for the
      nuclear localization signals. An in vitro binding assay was used to investigate
      the role of Vpr in docking of the HIV-1 preintegration complex (PIC) to the
      nuclear pore complex. Mutant HIV-1 PICs that lack Vpr were impaired in the
      ability to dock to isolated nuclei and recombinant nucleoporins. Although Vpr by
      itself associated with nucleoporins, the docking of Vpr+ PICs was dependent on
      karyopherin beta and was blocked by antibodies to beta. Vpr stabilized docking by
      preventing nucleoporin-stimulated dissociation of the import complex. These
      results suggest a biochemical mechanism for Vpr function in transport of the HIV
      1 genome across the nuclear pore complex.

PMID- 9582383
TI  - CD27, a member of the tumor necrosis factor receptor superfamily, activates NF
      kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2,
      TRAF5, and NF-kappaB-inducing kinase.
AB  - CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily and is
      expressed on T, B, and NK cells. The signal via CD27 plays pivotal roles in T-T
      and T-B cell interactions. Here we demonstrate that overexpression of CD27
      activates NF-kappaB and stress-activated protein kinase (SAPK)/c-Jun N-terminal
      kinase (JNK). Deletion analysis of the cytoplasmic domain of CD27 revealed that
      the C-terminal PIQEDYR motif was indispensable for both NF-kappaB and SAPK/JNK
      activation and was also required for the interaction with TNF receptor-associated
      factor (TRAF) 2 and TRAF5, both of which have been implicated in NF-kappaB
      activation by members of the TNF-R superfamily. Co-transfection of a dominant
      negative TRAF2 or TRAF5 blocked NF-kappaB and SAPK/JNK activation induced by
      CD27. Recently, a TRAF2-interacting kinase has been identified, termed NF-kappaB
      inducing kinase (NIK). A kinase-inactive mutant NIK blocked CD27-, TRAF2-, and
      TRAF5-mediated NF-kappaB and SAPK/JNK activation. These results indicate that
      TRAF2 and TRAF5 are involved in NF-kappaB and SAPK/JNK activation by CD27, and
      NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-kappaB and SAPK/JNK
      activation.

PMID- 9582384
TI  - Nerve growth factor induces rapid increases in functional cell surface low
      density lipoprotein receptor-related protein.
AB  - The low density lipoprotein receptor-related protein (LRP) is a large endocytic
      receptor that binds multiple ligands and is highly expressed in neurons. Several
      LRP ligands, including apolipoprotein E/lipoproteins and amyloid precursor
      protein, have been shown to participate either in Alzheimer's disease
      pathogenesis or pathology. However, factors that regulate LRP expression in
      neurons are unknown. In the current study, we analyzed the effects of nerve
      growth factor (NGF) treatment on LRP expression, distribution, and function
      within neurons in two neuronal cell lines. Our results show that NGF induces a
      rapid increase of cell surface LRP expression in a central nervous system-derived
      neuronal cell line, GT1-1 Trk, which was seen within 10 min and reached a maximum
      at about 1 h of NGF treatment. This increase of cell surface LRP expression is
      concomitant with an increase in the endocytic activity of LRP as measured via
      ligand uptake and degradation assays. We also found that the cytoplasmic tail of
      LRP is phosphorylated and that NGF rapidly increases the amount of
      phosphorylation. Furthermore, we detected a significant increase of LRP
      expression at the messenger RNA level following 24 h of NGF treatment. Both rapid
      and long term induction of LRP expression were also detected in peripheral
      nervous system-derived PC12 cells following NGF treatment. Taken together, our
      results demonstrate that NGF regulates LRP expression in neuronal cells.

PMID- 9582385
TI  - FORUM: Defining Goals and Criteria for Ecosystem-Based Management
AB  - / Identifying goals or targets for landscape and ecosystem management is now a
      widely recognized need that has received little systematic attention. At a micro
      level most planners and managers of both ecosystems and economies continue to
      pursue traditional goals and targets that miss many desirable characteristics of
      ecosystem-based management goals. Desirable characteristics of ecosystem and
      landscape management goals and targets include: addressing complexity,
      transdisciplinarity, and the dynamic nature of natural systems; reflecting the
      wide range of interests and goals that exist; recognizing goals and values and
      limits; involving people and being explainable and implementable in a consistent
      way to different people and groups; and evolving adaptively as conditions and
      knowledge change. Substantive and procedural goals can be distinguished; the
      latter supporting the former. Substantive goals can be grouped according to their
      relationship to system structure, organization, and process/dynamics, and their
      disciplinary or subsystemic breadth. These discussions are illustrated by a
      review of the goals of biodiversity, sustainability, ecological health, and
      integrity. An example of a hierarchical framework of procedural goals and
      objectives that supports achievement of substantive goals is also provided. The
      conclusion is that a parallel, linked system of substantive and procedural goals
      at different levels of complexity and disciplinarity is needed to facilitate
      ecosystem-based management.KEY WORDS: Ecosystem management; Goals and objectives;
      Assessment criteria

PMID- 9582386
TI  - Frames of Reference: A Metaphor for Analyzing and Interpreting Attitudes of
      Environmental Policy Makers and Policy Influencers
AB  - / The concept of frame of reference offers a potentially useful analytical
      metaphor in environmental management. This is illustrated by a case study in
      which attitudes of individuals involved in the management of trees in the New
      Zealand high country are classified into seven distinctive frames of reference.
      Some practical and theoretical implications of the use of the frame metaphor are
      explored, including its potential contribution to the emerg- ing field of
      communicative planning. KEY WORDS: Frames of reference; Environmental policy
      analysis; Metaphor; New Zealand high country

PMID- 9582387
TI  - Sampling Schemes for Policy Analyses Using Computer Simulation Experiments
AB  - / Evaluating the environmental and economic impacts of agricultural policies is
      not a simple task. A systematic approach to evaluation would include the effect
      of policy-dependent factors (such as tillage practices, crop rotations, and
      chemical use) as well as the effect of policy-independent covariates (such as
      weather, topography, and soil attributes) on response variables (such as amount
      of soil eroded or chemical leached into the groundwater). For comparison
      purposes, the effects of these input combinations on the response variable would
      have to be assessed under competing policy scenarios. Because the number of input
      combinations is high in most problems, and because policies to be evaluated are
      often not in use at the time of the study, practitioners have resorted to
      simulation experiments to generate data. However, generating data from simulation
      models is often costly and time consuming; thus, the number of input combinations
      in a study may be limiting even in simulation experiments. In this paper, we
      discuss the problem of designing computer simulation experiments that require
      generating data for just a fraction of the possible input combinations. We
      propose an approach that is based on subsampling the 1992 National Resources
      Inventory (NRI) points. We illustrate the procedure by assessing soil erosion in
      a situation where there are "observed" data [reported by the Natural Resources
      Conservation Service (NRCS)] for comparison. Estimates for soil erosion obtained
      using the procedure we propose are in good agreement with NRCS reported
      values.KEY WORDS: Metamodel; National Resources Inventory; Nonpoint source
      pollution

PMID- 9582388
TI  - PROFILE: The Use of a Simple Air Quality Index in the Helsinki Area, Finland
AB  - / A simple air quality index (AQI) was introduced for the Helsinki Metropolitan
      Area in 1993, in order to inform the public about the current air quality in an
      easily understood way. The pollutants included in the AQI are CO (1 and 8 h), NO2
      (1 and 24 h), SO2 (1 and 24 h), O3 (1 h) and PM10 (24 h). The AQI is linked to
      the new air quality guidelines in Finland. The AQI is based on acute health
      effects, but long-term effects on nature and materials are also taken into
      consideration. Subindices are calculated hourly for all pollutants and for a
      given hour the highest subindex becomes the AQI. AQI values are currently
      calculated for the center of Helsinki and for typical suburban areas.KEY WORDS:
      Air pollution; Air quality index; Guidelines; Helsinki; Finland

PMID- 9582389
TI  - Industry Response to the Challenge of Sustainability: The Case of the Canadian
      Nonferrous Mining Sector
AB  - / The paper investigates how the Canadian nonferrous sector is tackling the
      challenge of sustainable development. Although there is no consensus as to what
      sustainable development means in practice for management in the sector, at least
      three dimensions must be taken into account: (1) metals are recyclable, the
      availability of this resource is not a concern for the foreseeable future; (2)
      the need to minimize environmental impacts of metals exploration, extraction,
      transformation, consumption, and recycling; and (3) production activities should
      not be socially or culturally disruptive. The nonferrous mining industry faces
      several environmental problems. Some of the most significant are acid mine
      drainage, sulfur emissions, recycling, and metals toxicity. The industry has
      developed a number of responses to address these specific concerns as well as
      other more general challenges. Six strategies are described and analyzed: (1)
      research and development, (2) an effort of consensus building among stakeholders
      known as the Whitehorse Mining Initiative, (3) international networking, (4)
      active involvement in the development of environmental management standards, (5)
      management reorganization and (6) voluntary agreements. The importance of
      external factors in the shaping of corporate environmental management practices
      is discussed, in particular the role of government. Progress has been achieved in
      three areas: (1) managerial practices and organization, (2) reducing the impacts
      of ongoing operations and (3) minimizing future liabilities, but two significant
      fields of conflict remain, namely mining in wilderness areas and projects on
      aboriginal lands.KEY WORDS: Canada; Environmental management; Minerals industry;
      Nonferrous metals; Sustainable development; Whitehorse Mining Initiative

PMID- 9582390
TI  - Canadian Innovations in Siting Hazardous Waste Management Facilities
AB  - / Siting hazardous waste facilities is an extremely complex and difficult
      endeavor. Public aversion to the construction of these facilities in or near
      their community often results in concerted opposition, referred to as the NIMBY
      syndrome. For the most part, siting processes do not fail because of inadequate
      environmental or technical considerations, but because of the adversarial
      decision-making strategies employed by the proponents. Innovative siting
      processes used in the provinces of Alberta and Manitoba offer tangible evidence
      of the successful application of an innovative siting approach based on the
      principles of decentralization of decision-making authority and full and
      meaningful public involvement. The purpose of this paper is to evaluate four
      Canadian siting processes from the perspective of public participation and access
      to decision-making authority. Examples of siting processes related to hazardous
      waste management facilities are provided from the provinces of Alberta, Manitoba,
      British Columbia, and Ontario. Siting has evolved from approaches dominated by
      top-down decision making to increasing decentralized and pluralistic approaches.
      Focusing on social and political concerns of potentially affected communities and
      on the process of decision making itself are fundamental to achieving siting
      success. In Alberta initially, and later in Manitoba, this new "open approach" to
      siting has resulted in the construction of the first two comprehensive hazardous
      waste treatment facilities in Canada.KEY WORDS: Hazardous waste facilities;
      Siting methodologies; Public participation

PMID- 9582391
TI  - Coastal Environmental Impacts Brought About by Alterations to Freshwater Flow in
      the Gulf of Mexico
AB  - / Freshwater inflow is one of the most influential landscape processes affecting
      community structure and function in lagoons, estuaries, and deltas of the world;
      nevertheless there are few reviews of coastal impacts associated with altered
      freshwater inputs. A conceptual model of the possible influences of freshwater
      inflows on biogeochemical and trophic interactions was used to structure this
      review, evaluate dominant effects, and discuss tools for coastal management.
      Studies in the Gulf of Mexico were used to exemplify problems commonly
      encountered by coastal zone managers and scientists around the world. Landscape
      alteration, impacting the timing and volume of freshwater inflow, was found to be
      the most common stress on estuarine systems. Poorly planned upstream landscape
      alterations can impact wetland and open-water salinity patterns, nutrients,
      sediment fertility, bottom topography, dissolved oxygen, and concentrations of
      xenobiotics. These, in turn, influence productivity, structure, and behavior of
      coastal plant and animal populations. Common biogeochemical impacts include
      excessive stratification, eutrophication, sediment deprivation, hypoxia, and
      contamination. Common biological impacts include reduction in livable habitats,
      promotion of "exotic" species, and decreased diversity. New multiobjective
      statistical models and dynamic landscape simulations, used to conduct policy
      relevant experiments and integrate a wide variety of coastal data for freshwater
      inflow management, assume that optimum estuarine productivity and diversity is
      found somewhere between the stress associated with altered freshwater flow and
      the subsidy associated with natural flow. These models attempt to maximize the
      area of spatial overlap where favorable dynamic substrates, such as salinity,
      coincide with favorable fixed substrates, such as bottom topography. Based upon
      this principle of spatial overlap, a statistical performance model demonstrates
      how population vitality measurements (growth, survival, and reproduction) can be
      used to define sediment, freshwater, and nutrient loading limits. Similarly, a
      spatially articulate landscape simulation model demonstrates how cumulative
      impacts and ecosystem processes can be predicted as a function of changes in
      freshwater, sediment, and nutrient inflows.KEY WORDS: Resource management;
      Landscape impacts; Freshwater discharge; Coastal, ecosystem models; Coastal
      wetlands

PMID- 9582392
TI  - Agency-Community Partnership in Landcare: Lessons for State-Sponsored Citizen
      Resource Management
AB  - / With over 2500 Australian Landcare groups, 65,000 volunteer members, and
      considerable evidence of program impact, Landcare is an important example of
      state-sponsored rural development in a developed nation. The agency-community
      partnership is a fundamental element of Landcare and getting the partnership
      right is vital to long-term program success. After reviewing the emergence of
      Landcare in the state of Victoria, the author reports research from a 1995 survey
      of Victorian Landcare groups. Survey information highlighted the extent of agency
      group contact, the important roles agency staff played in many Landcare groups,
      and the positive impact of agency contact and government funding upon group
      activity. Large majorities of groups reported they were satisfied with their
      relationship with agency staff. However, a majority of groups reported money or
      materials provided to manage land and water degradation was inadequate. Recently
      proposed changes to the Landcare program will provide government funding of work
      on private property and may address this concern. A majority of groups also
      reported support for leadership and management training was inadequate and
      respondents emphasized the need to revise program guidelines that limit funding
      for group coordinators. This information highlighted the importance of
      articulating a practical model of community participation in Australia and
      adopting a systematic approach to providing agency support for Landcare groups.
      Reflecting upon the Landcare experience, the author suggests some of the key
      elements of a practical model of state-sponsored citizen resource management
      contributing to rural development.KEY WORDS: Landcare; Australia; Community
      participation; Rural development; Citizen resource management; Sustainable
      agriculture

PMID- 9582393
TI  - RESEARCH: Perceptions of Risk Associated with Use of Farm Chemicals: Implications
      for Conservation Initiatives
AB  - / Data were collected from 245 farmers within the Darby Creek hydrologic unit in
      central Ohio to assess perceptions of risk associated with use of farm chemicals.
      Farmers were asked to evaluate the level of risk associated with use of
      agricultural chemicals for water quality, food safety, food quality, health of
      applicator, health of farm animals, wildlife, beneficial plants, beneficial
      insects, and human health. Study findings revealed that respondents perceived use
      of farm chemicals posed little or no threat to any of the assessed items. A
      composite index was formulated from the responses to the nine items and was
      titled Perceived Risk. Variance in the Perceived Risk index was regressed against
      social learning variables. The findings revealed that approximately 32% of the
      variance was explained by the predictive variables included in the model. It was
      concluded that the theoretical perspective was somewhat useful for understanding
      perceptions held about agricultural chemical use at the farm level. The findings
      are discussed in the context of future conservation and educational-information
      programs within the study region.KEY WORDS: Risk perception; Risk assessment;
      Groundwater; Pesticide contamination; Food safety; Environmental quality

PMID- 9582394
TI  - Effects of Grazing Pressure on Succession Process and Productivity of Old Fields
      on Mediterranean Islands
AB  - / Five experimental sites, located on four islands of the Aegean archipelago,
      were selected in order to assess the grazing-mediated recovery of natural
      vegetation in old fields. Years after abandonment of cultivation ranged from 5 to
      40. Grazing pressure was proved of considerable magnitude in all but the
      Santorini site, which recovers without mediation of intense grazing. The percent
      plant cover was low in all sites (less than 25%). One spiny species, Poterium
      spinosum, competitive under conditions of overgrazing and fire, accounted for 70%
      85% of the total plant cover in all sites, except Santorini, where participation
      of spiny species was very low. In the recently abandoned sites, annuals accounted
      for 50%-60% of the standing biomass, but constituted only a tiny fraction in
      those abandoned for 30 years or more. This was not paralleled by any remarkable
      increase of the total plant cover. In fact, the yearly produced green biomass
      decreased with the years after abandonment. The productivity of old fields
      abandoned for a long time is insufficient to support the grazing animals present.
      This shortfall, given the animals' requirements, is most dramatic in Symi. The
      nonrecovering vegetation in the old fields of these mountainous islands
      constitutes a severe environmental threat; remedial measures appear
      imperative.KEY WORDS: Aegean; Poterium spinosum; Pastures; Petrall curves; Sheep;
      Goats; Plant cover

PMID- 9582395
TI  - Closure of Disputes in Assessments of Climate Change in The Netherlands
AB  - / This paper presents an analysis of the closure of visible disputes in the
      assessments of climate change in the Netherlands. We focus primarily on two key
      constituents of the assessments: the estimate of climate sensitivity and the
      inclusion of non-CO2 greenhouse gases in assessment studies. For the cases
      studied, we identify variability in the assessment reports in the Netherlands
      during the pre-IPCC period. In the Netherlands arena, the assessments in this
      period can be seen as exponents of two different lines, a Netherlands line and an
      international line. We seek to identify what factors were decisive in the
      selection processes that resulted in the closure of visible disputes (visible in
      or across the assessment reports) for both cases. Our analysis reveals a
      remarkable difference in the adoption behavior of two Dutch assessment groups
      despite a large overlap in membership. We provide evidence that it is not the
      paradigmatic predisposition of the experts in the committee that was decisive for
      the closure of visible disputes, but it was the context in which the experts
      operated and the commitments they had made in each setting. 

PMID- 9582396
TI  - Short-Term Influence of Tank Tracks on Vegetation and Microphytic Crusts in
      Shrubsteppe Habitat
AB  - / I examined vegetation and microphytic crust cover on two sites in burned and
      two sites in unburned big sagebrush (Artemisia tridentata Nutt.) habitat within
      the Idaho Army National Guard Orchard Training Area in southwestern Idaho. The
      purpose of this study was to determine the short-term (1-2 years) influence of
      tank tracks on vegetation and microphytic crusts in shrubsteppe habitat. The two
      types of tank tracks studied were divots (area where one track has been stopped
      or slowed to make a sharp turn) and straight-line tracks. Divots generally had a
      stronger influence on vegetation and microphytic crusts than did straight-line
      tracks. Tank tracks increased cover of bare ground, litter, and exotic annuals,
      and reduced cover of vegetation, perennial native grasses, sagebrush, and
      microphytic crusts. Increased bare ground and reduced cover of vegetation and
      microphytic crusts caused by tank tracks increase the potential for soil erosion
      and may reduce ecosystem productivity. Reduced sagebrush cover caused by tank
      tracks may reduce habitat quality for rodents. Tank tracks may also facilitate
      the invasion of exotic annuals into sagebrush habitat, increasing the potential
      for wildfire and subsequent habitat degradation. Thus, creation of divots and
      movement through sagebrush habitat by tanks should be minimized.KEY WORDS:
      Divots; Fire history; Idaho; Military; Sagebrush; Straight-line tracks

PMID- 9582397
TI  - Effects of Tracking by Armored Vehicles on Townsend's Ground Squirrels in the
      Orchard Training Area, Idaho, USA
AB  - / Maintaining raptor populations is a primary objective of the legislation that
      designates the Snake River Birds of Prey National Conservation Area. Army
      training activities could influence habitat quality for raptors by changing the
      density, productivity, or behavior of their Townsend's ground squirrel
      (Spermophilus townsendii) prey. These changes could occur directly or as a result
      of changes in the vegetation available as food and cover for the ground
      squirrels. We assessed the effects of long-term tracking by armored vehicles by
      comparing 9-ha areas in sagebrush (Artemisia tridentata) -dominated shrubsteppe
      and bluegrass (Poa secunda) -dominated grasslands subjected to low-intensity
      tracking for approximately 50 years with others that had not been tracked. We did
      not detect any effect on ground squirrel population dynamics associated with long
      term tracking. Although densities of adults and juveniles tended to be higher in
      the areas exposed to such tracking, we attribute this difference to other factors
      that varied spatially. To determine short-term (two-year) effects, we
      experimentally tracked two sagebrush and two grassland sites with an M-1 tank
      after animals had begun their inactive season. In the following two active
      seasons we monitored squirrel demography and behavior and vegetative
      characteristics on the experimentally tracked sites and compared the results with
      control sites. Although we experimentally tracked approximately 33% of the
      surface of each of four sites where ground squirrel densities were assessed, the
      tracking had a detectable effect only on some herbaceous perennials and did not
      influence ground squirrel densities or behavior significantly during the
      subsequent two active seasons. We conclude that tracking after the start of the
      inactive season is likely to influence ground squirrel demography or behavior
      only if vegetation cover is substantially changed by decreasing coverage of
      preferred food plants or increasing the coverage of annual grasses and forbs that
      are succulent for only a short time each year.KEY WORDS: Armored vehicle
      tracking; Ground squirrels; Spermophilus townsendii; Behavior; Vegetation;
      Population density effects

PMID- 9582398
TI  - Bird Use of Restoration and Reference Marshes Within the Barn Island Wildlife
      Management Area, Stonington, Connecticut, USA
AB  - / Tidal marshes have been actively restored in Connecticut for nearly 20 years,
      but evaluations of these projects are typically based solely on observations of
      vegetation change. A formerly impounded valley marsh at the Barn Island Wildlife
      Management Area is a notable exception; previous research at this site has also
      included assessments of primary productivity, macroinvertebrates, and use by
      fishes. To determine the effects of marsh restoration on higher trophic levels,
      we monitored bird use at five sites within the Barn Island complex, including
      both restoration and reference marshes. Use by summer bird populations within
      fixed plots was monitored over two years at all sites. Our principal focus was
      Impoundment One, a previously impounded valley marsh reopened to full tidal
      exchange in 1982. This restoration site supported a greater abundance of wetland
      birds than our other sites, indicating that it is at least equivalent to
      reference marshes within the same system for this ecological function. Moreover,
      the species richness of birds and their frequency of occurrence at Impoundment
      One was greater than at 11 other estuarine marshes in southeastern Connecticut
      surveyed in a related investigation. A second marsh, under restoration for
      approximately ten years, appears to be developing in a similar fashion. These
      results complement previous studies on vegetation, macroinvertebrates, and fish
      use in this system to show that, over time, the reintroduction of tidal flooding
      can effectively restore important ecological functions to previously impounded
      tidal marshes.KEY WORDS: Estuarine; Tidal marsh; Wetland birds; Restoration

PMID- 9582399
TI  - ENVIRONMENTAL AUDITING: Choosing Indicators of Natural Resource Condition: A Case
      Study in Arches National Park, Utah, USA
AB  - / Heavy visitor use in many areas of the world have necessitated development of
      ways to assess visitation impacts. Arches National Park recently completed a
      Visitor Experience and Resource Protection (VERP) plan. Integral to this plan was
      developing a method to identify biological indicators that would both measure
      visitor impacts and response to management actions. The process used in Arches
      for indicator selection is outlined here as a model applicableto many areas
      facing similar challenges. The steps were: (1) Vegetation types most used by
      visitors were identified. Impacted and unimpacted areas in these types were
      sampled, comparing vegetation and soil factors. (2) Variables found to differ
      significantly between compared sites were used as potential indicators. (3) Site
      specific criteria for indicators were developed, and potential indicators
      evaluated using these criteria. (4) Chosen indicators were further researched for
      ecological relevancy. (5) Final indicators were chosen, field tested, and
      monitoring sites designated. In Arches, indicators were chosen for monitoring
      annually (soil crust index, soil compaction, number of used social trails and
      soil aggregate stability) and every five years (vegetation cover and frequency;
      ground cover; soil chemistry; and plant tissue chemistry).KEY WORDS: Biological
      indicators; Recreation impacts; Recreation management; Desert soils; Trampling

PMID- 9582400
TI  - Predicting response to cancer chemotherapy: the role of p53.
AB  - Loss of wild-type p53 activity is thought to be a major predictor of failure to
      respond to radiotherapy and chemotherapy in various human cancers. This
      assumption is largely based on some cell-death studies in p53-knockout mice and
      on correlations of p53 status assessed by immunochemistry or single-strand
      conformational polymorphism (SSCP) analysis, and responses to therapy in human
      cancers in vivo. In principle, p53 may enhance chemosensitivity by promoting
      apoptosis via transcription-independent mechanisms as well as transcriptional
      activation of proapoptotic genes such as bax and transcriptional repression of
      antiapoptotic genes such as bcl-2. Drug-induced suicide mediated by the CD95/CD95
      ligand system may also involve a p53-controlled pathway. Yet, p53 may decrease
      chemosensitivity by promoting p21-mediated and p21-independent growth arrest, DNA
      repair, and differentiation, and by enhancing the transcription of antiapoptotic
      genes such as bcl-x. Cell-culture work indicates that the effects of altering the
      p53 status on chemosensitivity depend very much on the cellular context.
      Disruption of p53 function in otherwise normal, nonneoplastic cells may enhance
      rather than decrease chemosensitivity. However, targeted p53 gene disruption in
      some cell types obtained from p53-knockout mice results in enhanced rather than
      decreased sensitivity, e.g., to irradiation. Transformed cells that have retained
      wild-type p53 function tend to acquire chemoresistance when p53 function is
      disabled, with few exceptions. Thus, preexisting molecular alterations or
      consecutive accumulation of molecular alterations after loss of p53 rather than
      the loss of wild-type p53 activity per se may confer chemoresistence to tumor
      cells. Moreover, p53 accumulation resulting from the increased half-life of
      mutant p53 proteins can act as a gain-of-function mutation, presumably as a
      consequence of multiple protein-protein interactions. Finally, significant tumor
      cell-type- and drug-specific patterns of modulation of chemosensitivity by p53
      are beginning to emerge. Transfer of wild-type p53 genes into tumor cells
      commonly induces growth arrest but may render these cells relatively more
      resistant to most chemotherapeutic drugs. Therefore, careful experimental in
      vitro and in vivo studies are required before chemotherapy-supported p53 gene
      therapy for human cancer is introduced into clinical practice.

PMID- 9582401
TI  - The cell biology of liver fibrogenesis - an imbalance of proliferation, growth
      arrest and apoptosis of myofibroblasts.
AB  - Fibrosis following liver damage and factors influencing this process are
      discussed with special reference to hepatic stellate cells and their
      transformation to myo- fibroblasts.

PMID- 9582403
TI  - Different subpopulations of cholinergic and nitrergic myenteric neurones project
      to mucosa and circular muscle of the guinea-pig gastric fundus.
AB  - Since the stomach lacks a well-developed ganglionated submucous plexus, the
      somata of enteric neurones innervating the muscle or the mucosa have to be
      localised within the myenteric plexus. The aim of this study was to determine the
      projection pathways and the neurochemical coding of myenteric neurones
      innervating these different targets in the gastric fundus. Myenteric cell bodies
      projecting to the mucosa or the circular muscle were retrogradely labelled by
      mucosa or muscle application of the fluorescent tracer DiI and subsequently
      characterised by their immunoreactivity for choline acetyltransferase (ChAT),
      nitric oxide synthase (NOS), substance P (SP) and/or neuropeptide Y (NPY). On
      average 143+/-91 and 89+/-49 myenteric neurones were labelled from the mucosa and
      the circular muscle, respectively. DiI-labelled neurones were either ChAT- or NOS
      positive. DiI-labelled ChAT-positive neurones were mainly ascending and
      outnumbered NOS-positive neurones, which were mainly descending (79.3+/-6.2% vs
      20.7+/-6.2% for mucosa neurones; 69.3+/-11.1% vs 30.7+/-11.1% for muscle
      neurones). Three ChAT-positive subpopulations (ChAT/-, ChAT/SP, ChAT/NPY) and two
      NOS-positive subpopulations (NOS/-, NOS/NPY) were found. ChAT/SP neurones
      projected mainly to the circular muscle (36.1+/-11.9% of the cholinergic muscle
      neurones; mucosa projection: 8.0+/-2.1%), whereas ChAT/NPY neurones projected
      mainly to the mucosa (38.1+/-9. 2% of the cholinergic mucosa neurones; muscle
      projection: 5.7+/-2. 4%). NOS/- cells projected predominantly to the muscle. This
      study demonstrates polarised pathways in the myenteric plexus consisting of
      ascending ChAT and descending NOS cells that innervate the circular muscle and
      the mucosa of the gastric fundus. The ChAT/SP neurones might function as circular
      muscle motor neurones, whereas ChAT/NPY neurones might represent secretomotor
      neurones.

PMID- 9582402
TI  - Nonvagal origin of galanin-containing nerve terminals innervating striated muscle
      fibers of the rat esophagus.
AB  - We investigated the origin of galanin-positive nerve fibers on motor endplates in
      rat esophagus using anterograde 1,1'-dioleyl-3,3,3', 3'
      tetramethylindocarbocyanine methane sulfonate (DiI) tracing from the nucleus
      ambiguus combined with galanin immunocytochemistry and calcitonin gene-related
      peptide immunocytochemistry. To demonstrate spatial relationships of galanin
      positive nerve fibers to vagal and enteric nerve fibers on motor endplates, we
      combined galanin immunocytochemistry with calcitonin gene-related peptide
      immunostaining for labeling of vagal terminals, and vasoactive intestinal peptide
      immunoreactivity and NADPH-diaphorase histochemistry for demonstration of enteric
      nerve fibers. Within fine varicose nerve fibers, galanin was colocalized with
      vasoactive intestinal peptide and NADPH-diaphorase to a high degree and turned
      out to be completely separated from calcitonin gene-related peptide-positive or
      anterogradely DiI-labeled vagal motor terminals. These results indicate that the
      enteric nervous system is the most important and possibly the only source of
      galanin-positive nerve terminals on motor endplates in rat esophagus. Galanin may
      be, in addition to nitric oxide and vasoactive intestinal peptide, a mediator of
      the enteric coinnervation of striated muscle in this organ.

PMID- 9582404
TI  - Neuronal subpopulations in autonomic ganglia associated with the chicken ureter:
      an immunohistochemical study.
AB  - The neurochemical coding of neurones located in ganglia of the nerve trunk
      accompanying the chicken ureter was analysed and quantified using NADPH
      diaphorase reactivity and immunohistochemistry against tyrosine hydroxylase (TH),
      nitric oxide synthase (NOS), calbindin (CAL), vasoactive intestinal polypeptide
      (VIP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and calcitonin
      gene-related peptide (CGRP) in untreated or colchicine-treated preparation.
      Almost all neurones were either positive for TH (38%) or for SOM (60%). Only 4%
      of the neurones were both TH- and SOM-positive and 3% of the neurones exhibited
      neither TH nor SOM immunoreactivity. The relative numbers of NPY-, NOS-, CAL- and
      VIP-positive neurones were 57%, 28%, 14% and 7%, respectively. No SP- or CGRP
      positive neurones were observed. All NADPH-diaphorase-positive neurones expressed
      NOS immunoreactivity. Only in some TH-positive neurones was NPY and/or NOS found.
      Four major subpopulations were found in the ureteric ganglia. The SOM-positive
      neurones were subdivided into SOM/NPY/NOS- (28% of all neurones), SOM/NPY- (18%)
      and SOM/CAL/NPY-positive neurones (14%). A subpopulation of these peptid- ergic
      neurones also contained VIP. About 35% of the neurones contained TH only.
      Neurones of all subpopulations (72% of the neurones), except most of the CAL
      positive neurones, were encircled by dense plexus of varicose SP/CGRP-positive,
      presumably sensory nerve fibres. Dense plexus of VIP-positive fibres were
      observed around 89% of the neurones. The chemical coding of the neuronal
      subpopulations identified in the ganglia accompanying the chicken ureter
      resembled that observed in the ganglia of Remak's nerve but was remarkably
      different from that of the autonomic neurones described in mammalian species.

PMID- 9582405
TI  - Specific localization of gap junction protein, connexin45, in the deep muscular
      plexus of dog and rat small intestine.
AB  - Cellular networks of pacemaker activity in intestinal movements are still a
      matter of debate. Because gap-junctional intercellular communication in the
      intestinal wall may provide important clues for understanding regulatory
      mechanisms of intestinal movements, we have attempted to clarify the distribution
      patterns of three types of gap junction proteins. Using antibodies for
      connexin40, connexin43, connexin45, smooth muscle actin, and vimentin,
      immunocytochemical observations were made with the confocal laser scanning
      microscope on cryosections of fresh-frozen small intestine and colon of the dog
      and rat. Connexin 45 was localized along the deep muscular plexus of the small
      intestine in both dog and rat. Double labeling studies revealed that connexin45
      overlapped with vimentin -, but not actin-positive areas, indicating the
      fibroblast-like nature of the cells, rather than their being smooth muscle-like.
      Connexin43 immunoreactivity appeared along the smooth muscle cell surface in the
      outer circular layer of the small intestine of both animals. Connexin 40
      immunoreactivity was not observed in the muscle layer other than in the wall of
      large blood vessels. It is suggested that connexin45-expressing cells along the
      deep muscular plexus of dog and rat small intestine are likely to act as a
      constituent of a pacemaker system, which may include a conductive system, by
      forming a cellular network operating via specific types of gap junctions.

PMID- 9582406
TI  - Extraocular muscle in merosin-deficient muscular dystrophy: cation homeostasis is
      maintained but is not mechanistic in muscle sparing.
AB  - Extraocular muscle is uniquely spared from damage in merosin-deficient congenital
      muscular dystrophy. Using a murine model, we have tested the hypothesis that the
      maintenance of calcium homeostasis is mechanistic in extraocular muscle
      protection. Atomic absorption spectroscopy has demonstrated a strong correlation
      between the perturbation of calcium homeostasis in hindlimb muscle that is
      severely damaged and the absence of changes in calcium in extraocular muscle. If,
      as in other skeletal muscles, extraocular muscle fibers are destabilized by
      merosin deficiency, we would expect an increase in total muscle calcium coupled
      with an adaptive response in the high capacity/speed of the sarcoplasmic
      reticulum of the eye muscle. However, we have not observed the expected increases
      in total muscle calcium content, Ca2+-ATPase activity, Na+/Ca2+ exchanger
      content, or smooth ER Ca2+-ATPase content that are predicted by this model.
      Instead, these results indicate that the increased membrane permeability that
      characterizes, and is potentially mechanistic in, myofiber degeneration in
      muscular dystrophy does not occur in merosin-deficient extraocular muscle. Thus,
      the high-capacity calcium-scavenging systems are not primarily responsible for
      extraocular muscle protection in muscular dystrophy.

PMID- 9582407
TI  - Nerve fiber formation and catecholamine content in adult rat adrenal medullary
      transplants after treatment with NGF, NT-3, NT-4/5, bFGF, CNTF, and GDNF.
AB  - Adrenal chromaffin cells have been characterized by the ability to change the
      phenotype in response to neurotrophic factor stimulation. The adrenal gland
      expresses numerous trophic factors endogenously, but there is still a lack of
      knowledge as to how the adrenal medullary cells respond to these factors.
      Accordingly, we evaluated nerve fiber outgrowth and cell morphology, and measured
      catecholamine content in adult rat adrenal medullary tissue transplanted to the
      anterior chamber of the eye after exposure to neurotrophin-3 (NT-3), neurotrophin
      4/5 (NT-4/5), basic fibroblast growth factor (bFGF), ciliary neurotrophic factor
      (CNTF), or glial cell line-derived neurotrophic factor (GDNF) compared with the
      effects after exposure to recombinant human nerve growth factor (rhNGF). The
      results show that rhNGF was the most potent factor in inducing neurite outgrowth
      from the grafted chromaffin cells. CNTF was also a powerful inducer of nerve
      fiber formation, while NT-4/5, GDNF, and bFGF were less potent. NT-3 did not
      produce neurite outgrowth above that seen in vehicle-treated eyes. Combining two
      neurotrophins, rhNGF and NT-3, reduced nerve fiber formation. Tyrosine
      hydroxylase (TH) immunohistochemistry revealed good cell survival in all grafts,
      and no morphological differences were detected with the different treatments. The
      adrenaline: noradrenaline: dopamine ratio was approximately 49%: 49%: 2%,
      independent of treatment, and the catecholamine content was equal irrespective of
      treatment. In conclusion, all neurotrophic factors used, except for NT-3,
      promoted neurite outgrowth from adult rat chromaffin transplants. Differences in
      outgrowth induced by the various trophic factors did not, however, change the
      catecholamine content in grafts when analyzed together with the graft-derived
      nerve plexus.

PMID- 9582408
TI  - Intergranular bridges in the anterior pituitary cell and their possible
      involvement in Ca2+-induced granule-granule fusion.
AB  - Quick-freeze deep-etch electron microscopy showed the presence of bridge-like
      structures between adjacent secretory granules in rat anterior pituitary
      secretory cells. These intergranular bridges were variable in length and
      thickness. The finest bridges were 7-8 nm in length, while the longest ones were
      as long as 80 nm. Annexin II, one of the Ca2+-dependent phospholipid-binding
      proteins, is known to interlink between two membranes and induce aggregation of
      liposomes and chromaffin granules under the presence of Ca2+. In anterior
      pituitary cells, annexin II was detected by immunoelectron microscopy at the
      contact sites of secretory granules with other granules. The anterior pituitary
      cells treated under the presence of extracellular Ca2+ with Clostridium
      perfringens enterotoxin which induces Ca2+ influx showed multigranular
      exocytosis, i.e., multiple fusions of secretory granules with each other and with
      the plasma membrane. The granule-granule fusion in progress could be captured by
      the quick-freeze deep-etch technique. The membranes of adjacent secretory
      granules were partially fused at their contact sites where intergranular strands
      were no longer seen, while there existed intergranular strands between unfused
      portions of the granule membranes. From these results, we consider that the
      intergranular bridges, some of which may be composed of annexin II, are involved
      in Ca2+-induced granule-granule fusion in anterior pituitary cells.

PMID- 9582410
TI  - Ultrastructural, morphometrical and immunocytochemical analyses of the exocrine
      pancreas in a hibernating dormouse.
AB  - Pancreatic acinar cells of euthermic, hibernating and arousing individuals of the
      hazel dormouse Muscardinus avellanarius (Gliridae) have been observed at the
      electron-microscopic level and analysed by means of ultrastructural morphometry
      and immunocytochemistry in order to investigate possible fine structural changes
      of cellular components during periods of strikingly different degrees of
      metabolic activity. During hibernation, the cisternae of the rough endoplasmic
      reticulum (RER) flatten assuming a parallel pattern, the Golgi apparatus is
      extremely reduced and the mitochondria contain many electron-dense particles. The
      cell nuclei appear irregularly shaped, with deep indentations containing small
      zymogen granules. They also contain abundant coiled bodies and unusual
      constituents, such as amorphous bodies and dense granular bodies. Large numbers
      of zymogen granules occur in all animals. However, the acinar lumina are open and
      filled with zymogen only in euthermic animals, whereas, in hibernating and
      arousing individuals, they appear to be closed. Morphometrical analyses indicate
      that, in pancreatic acinar cells, nuclei and zymogen granules significantly
      decrease in size from euthermia to hibernation, probably reflecting a drastic
      decrease of metabolic activities, mainly protein synthesis and processing. In all
      the studied animals, immunocytochemistry with specific antibodies has revealed an
      increasing gradient in alpha-amylase content along the RER-Golgi-zymogen granule
      pathway, reflecting the protein concentration along the secretory pathway.
      Moreover, during deep hibernation, significantly larger amounts of alpha-amylase
      accumulate in RER and zymogen granules in comparison to the other seasonal phases
      analysed. Upon arousal, all cytoplasmic and nuclear constituents restore their
      euthermic aspect and all morphometrical and immunocytochemical parameters exhibit
      the euthermic values, thereby indicating a rapid resumption of metabolic
      activities.

PMID- 9582409
TI  - Morphological and immunocytochemical features of the pineal organ of C3H and
      C57BL mice at different stages of postnatal development.
AB  - Considerable progress is currently being made in elucidating the molecular basis
      of the circadian (photoneuroendocrine) system by use of transgenic mice generated
      from the inbred strains C57BL and C3H. As in all other vertebrate species, the
      pineal organ is an important component of the photoneuroendocrine system in these
      mouse strains, but very little is known about its morphological and
      immunocytochemical features. We therefore investigated the pineal organ and the
      adjacent epithalamic region of adult, 10-, and 5-day-old C57BL and C3H mice for S
      antigen, serotonin, and dopamine-ss-hydroxylase (DBH) immunoreactions. In adult
      animals, the pineal organ was more than 2 times bigger in C3H than in C57BL mice.
      In younger animals, this difference was already evident, but less pronounced. The
      S-antigen immunoreactivity was more intense in adult C3H than in C57BL mice. This
      difference developed with increasing age; it was not yet detectable in 5-day-old
      animals. The intensity of the serotonin immunoreaction was similar in both
      strains at all stages investigated. However, the serotonin immunoreaction was
      more pronounced in adult than in young animals. The relative DBH-immunoreactive
      area (used as a marker for the sympathetic innervation of the pineal organ) was
      much bigger in C3H than in C57BL mice; within each strain it remained relatively
      constant during postnatal development. Adult individuals of both strains
      contained S-antigen- and serotonin-immunoreactive cells in the habenular complex.
      Their number increased with age, but they were always more numerous in C3H. In
      conclusion, the study has shown considerable differences in pineal morphology
      between C3H and C57BL, which may be related to the well-known differen- ces in
      melatonin formation between these two strains.

PMID- 9582411
TI  - Morphological adaptations to induced changes in transepithelial sodium transport
      in chicken lower intestine (coprodeum): a study of resalination, aldosterone
      stimulation, and epithelial turnover.
AB  - Transepithelial sodium transport and epithelial morphology during short-term
      adaptation to resalination or aldosterone stimulation were studied in the chicken
      coprodeum. Coprodeum was sampled for light and electron microscopy after 0-3 days
      of resalination in hens on a low-NaCl diet and after 0-6 days of aldosterone
      stimulation in hens on a high-NaCl diet. Sodium transport was measured in vitro
      with Ussing chambers. Plasma osmolality and electrolyte concentrations were
      measured in aldosterone-stimulated hens. Epithelial proliferation and migration
      between 1 h and 16 days were investigated in chickens on high-NaCl and low-NaCl
      diets using a bromodeoxyuridine technique. Resalination abolished the otherwise
      high sodium transport within 1 day, while the height and number of microvilli, as
      well as the number of brush cells, decreased over 3 days. Aldosterone stimulation
      increased sodium transport, the height and number of microvilli, and the brush
      cell number. Bromodeoxyuridine studies indicated an epithelial cell turnover of
      more than 16 days. The results thus demonstrate that epithelial cells have an
      unusual capacity to adjust rap- idly to variations in sodium intake. A strong
      correlation between structure and function was apparent.

PMID- 9582412
TI  - Effects of modulation of tyrosine phosphorylation on brush border enzyme activity
      in human Caco-2 intestinal epithelial cells.
AB  - Intestinal epithelial cell differentiation is closely regulated during normal
      cell renewal, maturation, and malignant transformation. Since tyrosine
      phosphorylation influences differentiation in other cell types and has been
      reported to vary between crypt cells to differentiated villus tip cells, we
      investigated the influence of tyrosine phosphorylation in colonocyte
      differentiation, by using human colonic Caco-2 cells as a model and expression of
      the brush border enzymes alkaline phosphatase (AKP) and dipeptidyl peptidase
      (DPDD) as differentiation markers. We studied three tyrosine kinase inhibitors
      with different modes of action and specificities, viz., genistein, erbstatin
      analog (EA), and tyrphostin, and the tyrosine phosphatase inhibitor sodium
      orthovanadate. AKP- and DPDD-specific activities were assayed in protein-matched
      cell lysates by synthetic substrate digestion. We also correlated the effects of
      these agents on brush border enzyme activity with tyrosine phosphorylation of
      phosphoproteins by Western blotting. Genistein (5-75 mg/ml) dose-dependently
      stimulated AKP and DPDD with a maximal stimulation at 75 mg/ml by 158.6+/- 17.5%
      and 228.6+/-37.1% of control values, respectively (n=12, P<0.001). The inactive
      analog genistin had no effect. Tyrphostin (25 mM) similarly stimulated AKP and
      DPDD by 138. 6+/-6.6% and 131.8+/-1.5% of control values (n=12, P<0.001).
      Unexpectedly, EA (0.1-10 mM) had the opposite effect, inhibiting AKP- and DPDD
      specific activity significantly at 10 mM with a maximal 14.8+/-6.4% and 26.5+/
      2.5% of control values (n=12, each P<0.001). Sodium orthovanadate had a
      discordant effect on these two differentiation markers. Orthovanadate dose
      dependently increased AKP to a maximal 188.5+/-16.1% of basal activity at 1.5 mM
      but decreased DPDD activity at 1.5 mM to 47.2+/-3.8% (n=9, P<0.001 each). The
      effects of each agent were preserved when proliferation was blocked with
      mitomycin C, suggesting that the modulation of phenotype by these agents was
      independent of any effects of proliferation. The tyrosine phosphorylation of
      several phosphoprotein bands was affected differently by these agents. In
      particular, the tyrosine phosphorylation of one 70-kDa to 71-kDa band was
      increased by genistein and tyrophostin but deceased by EA. The different effects
      of these modulators of tyrosine kinase activity raise the possibility that at
      least two independent enzymes or pathways regulating tyrosine phosphorylation
      modulate intestinal epithelial differentiation. Furthermore, tyrosine
      phosphorylation of the 70-kDa to 71-kDa phosphoprotein may be important in the
      intracellular signaling by which intestinal epithelial cell differentiation is
      controlled.

PMID- 9582413
TI  - Quantitative changes in rat renin secretory granules after acute and chronic
      stimulation of the renin system.
AB  - In order to study the cellular mode of renin secretion, stereological methods
      were used to estimate number and volume of rat renin secretory granules during
      stimulation of the renin system. An acute decrease in renal perfusion pressure to
      40 mmHg for 5 min increased plasma renin concentration (PRC) twofold, but did not
      significantly change the number of renin granules per arteriole or the renin
      containing volume of the arteriole. Chronic stimulation was achieved by a
      combination of low-salt diet and inhibition of angiotensin-converting enzyme
      (ACE) for 14 days, and resulted in a 36-fold increase in PRC, a 20-fold increase
      in the number of granules per arteriole, and a 17-fold increase in the arteriolar
      volume that contained renin. An acute decrease in renal perfusion pressure to 40
      mmHg for 5 min in the chronically stimulated rats increased PRC further (1.6
      fold), and significantly reduced the number of granules per arteriole by 4000
      (45% reduction), but did not change the renin-containing arteriolar volume
      significantly. The average renin granule size was 0.35 microm3 with no
      significant differences among the groups. We conclude that recruited granular
      cells contribute significantly to renin release, and that all granular cells
      along the arteriole participate in secretory responses. The reduced number of
      renin granules after acute stimulation is compatible with exocytosis as the
      dominating mechanism of renin release.

PMID- 9582415
TI  - NADPH-diaphorase activity in the nervous system of the embryonic and juvenile
      pond snail, Lymnaea stagnalis.
AB  - Nicotinamide-adenine-dinucleotide-phosphate-diaphorase (NADPH-d) histochemistry
      has been applied in the present study to determine the distribution of putative
      nitric oxide (nitric oxide synthase)-producing cells during embryonic and early
      postembryonic development in the pond snail, Lymnaea stagnalis L., with special
      reference to the nervous system. The first NADPH-d-positive structures appear as
      early as 18% of development (E18, trochophore stage) and correspond to the pair
      of protonephridia. These structures later show disintegration, although after
      metamorphosis (E26=75%) staining of their individually spreading cells can be
      observed until hatching. Peripheral sensory neurons in the foot, mantle edge and
      lips, and their afferents projecting to the central nervous system reveal NADPH-d
      activity in the postmetamorphosis period (E25-E27=E60%-E80%) of embryogenesis.
      After hatching (P1-P3), a number of stained sensory cells appear in the pharynx
      and esophagus. Some NADPH-d positive neuronal perikarya occur in the pedal and
      pleural ganglia, and a few weakly stained cells in the cerebral and buccal
      ganglia of juvenile snails. At the same time, a continuous bundle of reactive
      fibers is formed in the neuropil both through and through around the
      circumesophageal ganglion ring. The localization of NADPH-d activity in the
      developing nervous system of Lymnaea suggests that nitric oxide participates
      mainly in sensory processes. However, its role in specific intraganglionic
      integrative events cannot be excluded following embryonic metamorphosis.

PMID- 9582414
TI  - Immunolocalization of steroidogenic enzymes (P450scc, P450c17, P450arom, and
      3beta-HSD) in immature and mature testes of rainbow trout (Oncorhynchus mykiss).
AB  - We examined the localization of steroidogenic cells in rainbow trout
      (Oncorhynchus mykiss) testis during spermatogenesis by using polyclonal
      antibodies generated against rainbow trout cholesterol side-chain cleavage enzyme
      cytochrome P450 (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD),
      17alpha-hydroxylase/C17,21 lyase (P450c17), and aromatase cytochrome P450
      (P450arom) as markers of steroid production. Since we had previously produced
      specific antibodies against 3beta-HSD and P450arom, antibodies against
      oligopeptides corresponding to C-terminal sequences of P450scc and P450c17,
      predicted from rainbow trout P450scc and P450c17 cDNAs, were produced in this
      study. These two antibodies recognized 54-kDa (P450scc) and 59-kDa (P450c17)
      bands specifically in several steroidogenic organs, i.e., testis, ovary, and
      interrenal tissue (head kidney) in Western blots. Immunohistochemically,
      immunoreactive P450scc, P450c17, and 3beta-HSD, but not P450arom, were found only
      in interstitial Leydig cells of immature and mature testes. Immunoreactive
      P450arom was not detected in either testis. This study suggests that Sertoli
      cells and germ cells of rainbow trout testis do not contain P450scc, P450c17,
      P450arom, or 3beta-HSD.

PMID- 9582416
TI  - Cytobiological studies on hemocyanin metabolism in the branchial heart complex of
      the common cuttlefish Sepia officinalis (Cephalopoda, Dibranchiata).
AB  - The present study confirms previous investigations that demonstrated a high
      copper content in the branchial heart and its appendage, and that gave the first
      indication that this organ complex might be involved in hemocyanin metabolism in
      Sepia officinalis L. Immunocytochemical localization of hemocyanin molecules
      within the endocytotic lysosomal system of the ovoid cells and tracer experiments
      with 125I-labeled Sepia hemocyanin suggest its endocytotic uptake. Energy
      dispersive X-ray microanalysis and histochemical methods reveal a high copper
      content within the ovoid cells of the branchial heart. In view of the turnover of
      the respiratory pigment in the branchial heart of Sepia officinalis L., we
      believe that the ovoid cells are a site of hemocyanin catabolism.

PMID- 9582417
TI  - Cellular origin of chlorinated diketopiperazines in the dictyoceratid sponge
      Dysidea herbacea (Keller).
AB  - The tropical marine sponge Dysidea herbacea (Keller) contains the filamentous
      unicellular cyanobacterium Oscillatoria spongeliae (Schulze) Hauck as an
      endosymbiont, plus numerous bacteria, both intracellular and extracellular.
      Archaeocytes and choanocytes are the major sponge cell types present. Density
      gradient centrifugation of glutaraldehyde-fixed cells with Percoll as the support
      medium has been used to separate the cyanobacterial symbiont from the sponge
      cells on the basis of their differing densities. The protocol also has the
      advantage of separating broken from intact cells of O. spongeliae. The lighter
      cell preparations contain archaeocytes and choanocytes together with damaged
      cyanobacterial cells, whereas heavier cell preparations contain intact
      cyanobacterial cells, with less than 1% contamination by sponge cells. Gas
      chromatography/mass spectrometry analysis has revealed that the terpene
      spirodysin is concentrated in preparations containing archaeocytes and
      choanocytes, whereas nuclear magnetic resonance analysis of the symbiont cell
      preparations has shown that they usually contain the chlorinated
      diketopiperazines, dihydrodysamide C and didechlorodihydrodysamide C, which are
      the characteristic metabolites of the sponge/symbiont association. However, one
      symbiont preparation, partitioned by a second Percoll gradient, has been found to
      be devoid of chlorinated diketopiperazines. The capability to synthesize
      secondary metabolites may depend on the physiological state of the symbiont;
      alternatively, there may be two closely related cyanobacterial strains within the
      sponge tissue.

PMID- 9582418
TI  - De novo expression of MHC class II molecules by microglial cells during acute rat
      renal allograft rejection.
AB  - The expression of MHC class I and class II molecules in the cerebral cortex of
      rats was investigated at daily intervals from day 3 to day 6 after fully
      allogeneic (DA-->LEW) and isogeneic (LEW-->LEW) kidney transplantation. MHC class
      II molecules were temporarily induced on the previously negative microglial cells
      and on the endothelia of arterioles and venules during acute rejection. On the
      endothelia of all brain vessels MHC class I expression was enhanced. MHC class I+
      cells with microglial cell morphology were discernible within the diffusely MHC
      class I+ brain parenchyma. In contrast, the brain parenchyma of isograft
      recipients and untreated control animals did not express detectable levels of MHC
      molecules. In conclusion, we demonstrate that a strong immune reaction in the
      periphery is able to activate microglial cells in the central nervous system.

PMID- 9582419
TI  - Calretinin-immunoreactive laminar nerve endings in the laryngeal mucosa of the
      rat.
AB  - The distribution of laminar nerve endings that contained immunoreactive
      calretinin was examined in the laryngeal mucosa of the adult rat. In whole-mount
      preparations, the immunoreactive laminar endings were distributed in the
      supraglottic region but not in the subglottic region. The laminar endings that
      arose from thick nerve fibers with or without swellings were identified as
      corpuscles with many variform terminal arborizations. They appeared to be located
      at the interface between the epithelium and the subepithelial connective tissue.
      The terminals were scattered under the basal lamina of the epithelium, and some
      of them were located within the epithelial layer. Immunoelectron microscopy
      revealed that both sub- and intraepithelial immunoreactive terminals that were
      filled with mitochondria were partly or totally ensheathed by Schwann cell
      processes. The denervation experiments, in which the superior laryngeal nerve was
      cut unilaterally or bilaterally, suggested that the laminar endings originate
      from the superior laryngeal nerve with strict ipsilateral innervation. The
      laminar endings might be associated with detection of changes in pressure in the
      laryngeal cavity or chemical stimuli.

PMID- 9582420
TI  - Changes in neurotrophin-3 messenger RNA expression patterns in the prenatal rat
      tongue suggest guidance of developing somatosensory nerves to their final
      targets.
AB  - While brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) has been
      localized in the developing gustatory epithelium, little information is available
      about neurotrophin-3 (NT-3) mRNA expression pattern in the prenatal developing
      gustatory and lingual epithelium. In the present study, using in situ
      hybridization histochemistry, we report on NT-3 mRNA expression in the tongue of
      rats. At embryonic day (E) 13-17, NT-3 mRNA was expressed subepithelially in the
      periphery of the developing tongue, as well as among developing muscle. At E19,
      there was a shift in the expression of NT-3 mRNA. It was then expressed in the
      surface epithelium of the developing tongue in the developing filiform papillae
      and, in higher concentrations, in top-surface and fringe epithelium of the
      developing circumvallate papillae, and top- and lateral-surface epithelium of the
      developing fungiform papillae. NT-3 mRNA expression in areas rich in
      somatosensory innervation of the tongue, as well as its specific expression in
      defined regions compared with BDNF, and the decreased labeling noted from
      prenatal and early postnatal animals to adults indicate a specific role for NT-3
      in the development of lingual somatosensory innervation, as well as for
      maintenance of this innervation.

PMID- 9582421
TI  - Identification of a novel serine protease-like molecule in human brain.
AB  - Proteolysis of the amyloid beta protein precursor (APP) is a key event in the
      development of Alzheimer's disease. In our search for proteases that can cleave
      APP and liberate the amino terminus of the amyloidogenic beta protein, we
      characterized a calcium-dependent serine protease (CASP) which is present in
      reactive astrocytes and cross-reacts with anti-cathepsin G antibodies. We wanted
      to take advantage of this cross-reactivity to clone the cDNA of CASP and
      eventually evaluate its tissue distribution. Screening of two human fetal brain
      cDNA libraries with anti-cathepsin G antibodies led to the identification of a
      cDNA coding for a novel protein whose only homology to known proteins is to the
      active site of trypsin-type serine proteases. We called this protein the novel
      serine protease (NSP). NSP exists in at least three differentially spliced forms,
      one of which is expressed predominantly in brain and testis. Immunohistochemistry
      and immunoprecipitation with antibodies generated against NSP show that it is
      expressed and secreted by a variety of cells and that, in brain, it is found
      primarily in cerebrovascular smooth muscle cells and reactive astrocytes.

PMID- 9582422
TI  - Apoptosis of hippocampal neurons after amygdala kindled seizures.
AB  - Seizure-induced neuronal damage may involve both excitotoxic and apoptotic
      (programmed cell death) mechanisms. In the present study, we used an amygdala
      kindled seizure model to study whether apoptotic cell death occurs. To evaluate
      apoptosis, we counted the numbers of cells that had DNA fragments labeled at the
      3' end with digoxigenin using terminal transferase (ApopTag, Oncor).
      Additionally, the expression of Bax and Bcl-2, two genes associated with
      apoptotic cell death, was also measured following kindled seizures. We found that
      the number of ApopTag-positive cells in the hippocampus increased 30.4% after one
      kindled seizure and 82.5% after 20 seizures compared to sham controls. The
      ApopTag-labeled cells could be mainly interneurons of the hippocampal formation,
      although additional studies are required. Preferential vulnerability of
      inhibitory interneurons is consistent with previous studies on seizure-induced
      cell loss. These results, coupled with our findings that the ratio of Bax/Bcl-2
      expression is increased in the hippocampus by seizures, suggest that apoptosis of
      hippocampal interneurons may lead to dysinhibition in the hippocampus and
      increased seizure susceptibility.

PMID- 9582423
TI  - Expression patterns of voltage-dependent calcium channel alpha 1 subunits (alpha
      1A-alpha 1E) mRNA in rat retina.
AB  - The transcript levels of the genes encoding for the different alpha1 (alpha1A
      alpha1E) subunits of voltage-dependent calcium channels (VDCCs) were studied in
      the retina of the rat using RT-PCR, Northern blotting, and in situ hybridization.
      Abundant expression of alpha1A and alpha1B was found with RT-PCR and on Northern
      blots of total retina RNA, corresponding with high expression levels in all
      nuclear layers (outer and inner nuclear layers and the ganglion cell layer) of
      the retina. VDCC alpha1D mRNA was also present in all nuclear layers of the
      retina but at less abundant levels than alpha1A or alpha1B. Expression level of
      alpha1C in the retina was low as deduced from a faint Northern blot signal and a
      moderate yield after PCR amplification. VDCC alpha1E specific amplification of
      retinal cDNA yielded a longer product (designated alpha1E-L) than obtained from
      the hippocampus. Nucleotide sequencing of this PCR product revealed a 129 bp
      insert which is largely homologous (97%) with a previously described insert in
      the same position in human alpha1E cDNA. In situ hybridization in rat brain
      showed a differential expression pattern of the long and short variants of
      alpha1E mRNA. Northern blotting of retinal RNA confirmed the absence of the short
      variant (alpha1E-S), while alpha1E-L was present at low levels. In situ
      hybridization detected a significant level of expression of alpha1E-L in the
      inner nuclear layer. The prevalent expression of alpha1A and alpha1B, and to a
      lesser extent, of alpha1D, indicates that P/Q-, N-, and L-type calcium currents
      play a prominent role in the various cell types involved in the retinal signal
      transduction pathway. The absence of alpha1C transcript in the retina suggests
      that the slowly inactivating L-type calcium currents involved in neurotransmitter
      release from the terminals of photoreceptors and bipolar cells may be encoded by
      the alpha1D isoform.

PMID- 9582424
TI  - Time course of morphine withdrawal and preproenkephalin gene expression in the
      periaqueductal gray of rats.
AB  - We have previously reported the increase of preproenkephalin (PPE) mRNA in the
      caudal periaqueductal gray (PAG) of rats during morphine withdrawal. In this
      study, it was further evidenced that PPE mRNA in the caudal PAG was not increased
      by various kinds of stressor, suggesting that the increase in PPE mRNA in the
      caudal PAG is specific to morphine withdrawal. In order to investigate the
      physiological significance of the increase of PPE mRNA in the caudal PAG, we
      compared the time course of the increase of PPE mRNA in the caudal PAG with that
      of naloxone-precipitated or spontaneous morphine withdrawal signs. The increase
      of plasma corticosterone (PCS: 52 and 52 microg/100 ml; control group, 18 and 15
      microg/100 ml) and body weight loss (-6 and -9%; control group, 0 and -1%) were
      observed but PPE mRNA increase was not detected 1 and 2 h after naloxone in
      morphine treated rats. PPE mRNA increased by 37 to 56%, while PCS elevation and
      body weight loss gradually diminished 4 h to 2 days after naloxone. A total of 12
      h after spontaneous withdrawal, PCS was prominently increased (51 microg/100 ml;
      control group, 12 microg/100 ml), but body weight and PPE mRNA were not affected.
      One day after spontaneous withdrawal, PCS elevation (38 microg/100 ml; control
      group, 8 microg/100 ml) and body weight loss (-5%; control group, +3%) were
      observed and PPE mRNA also increased by 42%. Two to 3 days after the final
      morphine injection, PCS recovered to control level and body weight loss gradually
      disappeared, while PPE mRNA was still increased by 74 to 46%. These results
      suggest that PPE gene expression in the caudal PAG is stimulated in the
      recuperative phase of these morphine withdrawal signs.

PMID- 9582426
TI  - mu-Opioid receptor down-regulation and cAMP-dependent protein kinase
      phosphorylation in a mouse model of chronic morphine tolerance.
AB  - Results of radioligand binding and transfected receptor studies indicate that mu
      receptor down-regulation and phosphorylation may be critical to the expression of
      morphine tolerance. In this study, an animal model of morphine tolerance was used
      to correlate antinociception with changes in receptor number and phosphorylation
      state. mu-Opioid receptor protein was quantitated by Western immunoassay of
      brainstem tissue from morphine-treated mice. Degree of receptor phosphorylation
      was assessed using immunoprecipitation (IP) of the receptor followed by back
      phosphorylation. Acutely administered morphine produced no changes in mu-receptor
      quantity. Chronic morphine administration resulted in a 50% reduction in receptor
      protein quantity over placebo-treated samples. Back-phosphorylation experiments
      showed a drop in cAMP-dependent protein kinase A (PKA)-induced receptor
      phosphorylation shortly after acute morphine administration, followed by a
      naloxone-reversible increase in phosphorylation of the receptor that correlated
      with the onset of antinociception. Chronic morphine administration resulted in a
      decrease in PKA-induced phosphorylation of the mu-receptor. Since it has been
      shown that PKA activity is enhanced in the brains of morphine-tolerant mice, this
      decrease in mu-receptor phosphorylation suggests that the mu-receptor may be
      structurally or conformationally altered in the morphine-tolerant state.

PMID- 9582425
TI  - Expression of cholinergic markers in the pons of Flinders rats.
AB  - The Flinders sensitive line of rats (FSL rats) have an altered REM sleep pattern
      which includes a shorter REM sleep latency and an increased percentage of REM
      sleep [R.M. Benca, D.H. Overstreet, M.A. Gilliland, D. Russell, B.M. Bergmann,
      W.H. Obermeyer, Increased basal REM sleep but no difference in dark induction or
      light suppression of REM sleep in Flinders rats with cholinergic
      supersensitivity, Neuropsychopharmacology 15 (1996) 45-51; P.J. Shiromani, D.H.
      Overstreet, D. Levy, C.A. Goodrich, S.A. Campbell, J. C. Gillin, Increased REM
      sleep in rats selectively bred for cholinergic hyperactivity,
      Neuropsychopharmacology 1 (1988) 127-133]. Cholinergic mechanisms have been
      implicated in REM sleep generation [reviewed in P.J. Shiromani, J.C. Gillin, S.J.
      Henriksen, Acetylcholine and the regulation of REM sleep: basic mechanisms and
      clinical implication for affective illness and narcolepsy, Annu. Rev. Pharmacol.
      Toxicol. 27 (1987) 137-156]. In the present study, specific aspects of the
      cholinergic system were examined in the pontine region of the FSL rats. The
      number of cholinergic neurons in the LDT and PPT were not different in FSL and
      control rats. Analysis of steady state levels of mRNAs encoding the acetylcholine
      synthesizing protein, choline acetyltransferase (ChAT) or the m2, m3 and m5
      muscarinic receptor subtypes were also comparable in FSL and control rats. These
      data raise the possibility that the cellular events underlying the altered REM
      sleep pattern in FSL rats may include mechanisms that effect the muscarinic or
      nicotinic receptor in the pons.

PMID- 9582427
TI  - Analysis of the promoter region of the murine complement factor H gene.
AB  - We have used the luciferase system to assay basal promoter activity of the murine
      factor H gene. Based on the results from luciferase assays with clones of 13
      nested deletions, a 242-bp region that appeared to contain an enhancer element
      was subcloned upstream of a heterologous promoter and was shown to enhance
      transcription. A 26-bp fragment from this region was shifted in electrophoretic
      mobility assays, and this fragment contains a consensus sequence for the
      adenovirus major late transcription factor/upstream stimulatory factor
      (MLTF/USF). This fragment had enhancing activity in a minimal factor H promoter
      construct, demonstrating that it is a major enhancer of the factor H gene in
      murine liver cells.

PMID- 9582428
TI  - Cloning of glucocorticoid receptor and mineralocorticoid receptor cDNA and gene
      expression in the central nervous system of the tree shrew (Tupaia belangeri).
AB  - The glucocorticoid (GR) and the mineralocorticoid (MR) receptor mediate
      corticosteroid actions in the mammalian brain. Here, we report the sequence and
      distribution of both receptor subtype mRNAs in the central nervous system of the
      tree shrew Tupaia belangeri, a non-rodent mammal, phylogenetically located
      between insectivores and primates. The specific glucocorticoid and
      mineralocorticoid receptor cDNAs were cloned, employing polymerase chain reaction
      (PCR) based methods. The GR cDNA and MR cDNA encode the 776-amino acid (aa) and
      977-aa receptor, respectively. Comparisons of both GR and MR with corresponding
      cDNA-sequences of other species revealed the highest homology to the human
      equivalents (GR: 90%, MR: 89% nucleotide sequence identity of the coding
      regions). The localization of GR and MR mRNA in tree shrew brain was investigated
      by in situ hybridization using 35S-labeled riboprobes. The GR mRNA is widely
      distributed throughout all observed brain areas, with high signal intensities in
      the dentate gyrus, piriform cortex, cerebellum, anterior pituitary, subfornical
      organ and pineal gland. Whereas, moderate expression of GR mRNA was noted in
      region CA1 of the hippocampus, region CA3 displayed only low signal intensity. MR
      mRNA hybridization is mainly restricted to the strongly labeled hippocampal
      formation, but in contrast to the localization pattern found in rat, higher
      signal intensities are detected in field CA1 than in CA3. These data indicate
      that both GR and MR mRNAs are highly expressed in tree shrew brain with a species
      specific expression pattern.

PMID- 9582429
TI  - Characterization of two Sp1 binding sites of the human sex determining SRY
      promoter.
AB  - To investigate the molecular basis of the human SRY gene regulation, we have
      examined the significance of two potential binding sites for the transcription
      factor Sp1 (Sp1A: -124 to -131 and Sp1B: -147 to -154) by DNase I footprinting
      and gel mobility shift assays. Cotransfection experiments in Drosophila SL2 cells
      implicated Sp1 protein in the transcriptional activation of the SRY promoter.

PMID- 9582430
TI  - A new splicing variant of a type III POU gene from zebrafish encodes a POU
      protein with a distinct C-terminal.
AB  - A zebrafish POU protein cDNA clone was isolated and sequenced. It appears to be a
      novel splicing variant of the previously reported zebrafish POU gene zp-12. There
      are four splicing variants and at least three of them lead to different C
      terminal amino acid sequences. The four splicing variants are differentially
      regulated during development, indicating that they may be functionally
      diversified.

PMID- 9582431
TI  - NT-3 regulates expression of Brn3a but not Brn3b in developing mouse trigeminal
      sensory neurons.
AB  - We have used a quantitative RT-PCR approach to determine the levels of Brn3a and
      Brn3b POU domain transcription factor mRNAs in the developing mouse trigeminal
      ganglion from E10 to E18. Using low density neuronal cultures, we have shown that
      NT-3 can regulate the expression of Brn3a mRNA in trigeminal neurons during the
      periods that they are differentiating and innervating their peripheral and
      central targets. In contrast to Brn3a, Brn3b mRNA is expressed at extremely low
      levels in the early trigeminal ganglion. Trigeminal neurons from early ganglia
      express low levels of Brn3b mRNA in culture and do not up-regulate Brn3b mRNA in
      response to a number of growth factors and experimental conditions. However, at
      later ages, when in vivo levels of Brn3b mRNA are high, FGF2, TGFbeta1 and
      retinoic acid all up-regulate Brn3b mRNA expression in cultured trigeminal
      neurons. Since NT-3 regulates the developmental expression of Brn3a, Brn3a may
      mediate some of the effects that NT-3 exerts on sensory neurons and their
      progenitors. Similarly, Brn3b may mediate some of the effects that FGF2, TGFbeta1
      and retinoic acid have on neurons.

PMID- 9582432
TI  - Characterization of Bradyrhizobium japonicum pcaBDC genes involved in 4
      hydroxybenzoate degradation.
AB  - The pca structural genes encode enzymes that participate in the conversion of
      protocatechuate to succinate and acetylcoenzyme A. A 3. 05-kb region of the
      Bradyrhizobium japonicum strain USDA110 genome has been characterized, which
      contains the pcaB, pcaD and pcaC genes. The predicted protein sequences of the
      three genes have extensive homologies with beta-carboxy-cis,cis-muconate
      cycloisomerase (PcaB), beta-ketodiapate enol-lactone hydrolase (PcaD), and gamma
      carboxymuconolactone decarboxylase (PcaC), respectively, from Acinetobacter
      calcoaceticus and Pseudomonas putida. The DNA sequence revealed that the pca
      genes are probably arranged in a single transcriptional unit, pcaBDC, similar to
      that described in P. putida. A pcaB deletion mutant constructed by marker
      exchange mutagenesis lost the ability to use 4-hydroxybenzoate or protocatechuate
      as the only carbon source, demonstrating functionality of the characterized genes
      in catabolism of hydroxyaromatics by B. japonicum. Furthermore, 4-hydroxybenzoate
      and protocatechuate became toxic for the pcaB mutant, indicating that
      hydroxyaromatics catabolism serves both nutritional and detoxifying purposes.

PMID- 9582433
TI  - The cbaAB genes for bo3-type cytochrome c oxidase in Bacillus stearothermophilus.
AB  - Structural genes were cloned for cytochrome bo3-type cytochrome c oxidase
      recently isolated from a Gram-positive thermophile Bacillus stearothermophilus.
      Sequencing and Northern blotting analyses indicated that the two genes cbaA and
      cbaB composed an operon encoding for subunits I and II, respectively, and that
      the oxidase was SoxB-type. They are the first genes for a SoxB-type cytochrome c
      oxidase whose natural substrate is known.

PMID- 9582434
TI  - Localization and seizure-regulation of integrin beta 1 mRNA in adult rat brain.
AB  - Recent findings indicate that RGD-binding integrin receptors play a critical role
      in the maintenance of long-term potentiation but the identity and location of the
      integrin proteins involved are not known. The integrin beta1 is of particular
      interest in regard to synaptic plasticity because it is a component of many of
      the RGD-binding integrins and beta1-immunoreactivity has been localized within
      synaptic density fractions. The present study used in situ hybridization to
      evaluate the distribution of beta1 mRNA in adult rat brain and to determine if
      expression is altered by seizures. In untreated rats, beta1 mRNA is present at
      high levels in the ventricular epithelium and discrete neuronal groups including
      the magnocellular hypothalamic and efferent cranial nerve nuclei and the
      cerebellar Purkinje cells. Hybridization was less dense in the substantia nigra
      and hippocampal stratum pyramidale and low but present throughout the gray
      matter. Limbic seizures increased beta1 cRNA labeling of both neurons (e.g.,
      hippocampal stratum pyramidale) and astroglial cells from 8 h through 48 h after
      seizure onset. These results indicate that in adult rat brain, beta1 mRNA is
      expressed by both neurons and glia; neuronal expression is highest in
      hypothalamic and peripherally projecting neurons capable of substantial
      morphological plasticity. Seizure effects demonstrate that beta1 is positively
      regulated by activity, and suggest that activity-dependent expression may play a
      role in synaptic plasticity in the adult brain.

PMID- 9582435
TI  - Cell type specific repression of the varicella zoster virus immediate early gene
      62 promoter by the cellular Oct-2 transcription factor.
AB  - The cellular transcription factor Oct-2.1 has previously been shown to repress
      the transactivation of the varicella zoster virus (VZV) immediate early gene
      promoter by viral transactivators but not to inhibit its basal activity. In the
      case of the related virus herpes simplex virus (HSV), the effect of Oct-2 on the
      IE promoters has been shown to be cell type specific and to differ between the
      different alternatively spliced forms of Oct-2. Here we show that as well as Oct
      2.1, the Oct-2.4 and 2.5 isoforms which are expressed in neuronal cells can
      inhibit transactivation of the VZV immediate early promoter regardless of the
      cell type used. In contrast, all the isoforms of Oct-2 can inhibit basal activity
      of the VZV promoter in neuronal cells but not in other cell types indicating that
      this effect is cell type specific. These effects are discussed in terms of the
      differential regulation of latent infections with HSV or VZV in dorsal root
      ganglia.

PMID- 9582436
TI  - cDNA sequence and expression of the mouse alpha1(V) collagen gene (Col5a1).
AB  - Several overlapping cDNA clones corresponding to the entire coding sequence of
      the mouse alpha1(V) collagen gene (Col5a1) were isolated. The conceptual amino
      acid translation indicated a high degree of sequence identity (94%) with the
      human alpha1(V) chain. All of the important structures previously noted in the
      human alpha1(V) chain were also conserved in the mouse chain. The alpha1(V)
      transcripts were easily detected in mouse embryos as early as 11 days post coitum
      (d.p.c.). The transcripts were widely distributed in non-cartilaginous and
      cartilaginous tissues. Finally, we calculated the ratio of transcripts of
      alpha1(V):alpha2(V):alpha1(XI) in the calvaria and tongue of 18 d.p.c. embryos
      using the competitive reverse transcription-polymerase chain reaction (RT-PCR)
      technique. The results raised the possibility that there are at least two
      different kind of types V/XI collagen heterotrimers in mouse embryonic tissues.

PMID- 9582437
TI  - Identification of the pro-oncogene stathmin/op18 mRNA in the brain of
      mitochondrial Mn-superoxide dismutase-deficient mice by a modified differential
      display PCR.
AB  - Differential gene expression plays a critical role in many biological processes.
      To facilitate the screening of the entire mRNA species for cloning differentially
      expressed genes, we have made an effort to merge two polymerase chain reaction
      (PCR)-based methods, differential display (DD) and arbitrarily primed RNA
      fingerprinting (APR-FP), with some modifications. Using this modified method to
      screen the mRNAs of the brain tissues of manganese superoxide dismutase (MnSOD)
      deficient mice, we found several differentially expressed mRNA species. One mRNA
      species that was further analyzed by Northern hybridization and sequencing, and
      was confirmed to be induced only in the brain of MnSOD-deficient mice, encoded
      stathmin/op18. The MnSOD deficiency causes oxidative stress and mitochondrial
      dysfunction. Thus, the induction of stathmin/op18, a gene linked with microtubule
      catastrophe (disassembly) and often upregulated in neoplastic tissues and
      proliferating cells, may provide some understanding of the pathological changes
      in the brain of MnSOD-deficient mice.

PMID- 9582438
TI  - Differential effects on D2 dopamine receptor and prolactin gene expression by
      haloperidol and aripiprazole in the rat pituitary.
AB  - [3H]Spiperone-binding assay to D2 receptors and quantitative ribonuclease
      protection assay for both isoforms (D2L and D2S receptor) of the D2 receptor mRNA
      and the prolactin mRNA were performed on pituitaries from the control rat and
      from the rat injected orally daily with either haloperidol (2 mg/kg) or
      aripiprazole (24 mg/kg) for 21 days. Haloperidol treatment increased the
      [3H]spiperone-binding by 28%, the levels of D2L and D2S receptor mRNA by 41% and
      38%, respectively, and the level of prolactin mRNA by 26%. In contrast, the
      treatment with aripiprazole, a newly developed atypical antipsychotic with
      reduced side effects, decreased the [3H]spiperone-binding by 24% and the levels
      of D2L and D2S receptor mRNA by 23% and 23%, respectively, and did not have any
      effect on the level of prolactin mRNA. The same treatment with sulpiride (100
      mg/kg) increased the levels of D2L and D2S receptor mRNA by 59% and 62%,
      respectively, but treatment with clozapine (25 mg/kg) did not cause any effect.
      Neither treatment changed the ratio of the level of D2S receptor mRNA to the
      level of D2L receptor mRNA in the pituitary. These findings indicate that D2
      receptor densities in the pituitary are influenced differentially by the
      treatment with these antipsychotics, which could be induced at least partly by
      the changes in the levels of mRNA without any effects on the splicing mechanisms
      and thus affect the plasticity of the prolactin mRNA expression. The inhibitory
      effects of chronic aripiprazole treatment on D2 receptors in the pituitary might
      underlie this drug's clinical property of reduced hyperprolactinemia side effect.

PMID- 9582439
TI  - Psoralen crosslinking of active and inactive sea urchin histone and rRNA genes.
AB  - Chromatin structure is highly correlated with the transcriptional activity of
      specific genes. For example, it has been found that the regularity of nucleosome
      spacing is compromised when genes are transcribed. The rRNA genes from fungi,
      plants, and animals give distinctly bimodal distributions of psoralen
      crosslinking, which has led to the suggestion that these genes might be largely
      devoid of nucleosomes when transcriptionally active. We investigated the
      chromatin structure of the multicopy rRNA and histone genes during sea urchin
      early embryogenesis. The rRNA genes, which are weakly expressed, give a unimodal
      distribution of weak psoralen crosslinking, in contrast to the situation in all
      other organisms studied. The early histone genes were more accessible to psoralen
      crosslinking when active than inactive. The pattern of crosslinking suggests that
      these polII genes have a homogeneous structure and are still highly protected by
      nucleosomes when in the active conformation, unlike the situation in polI genes.

PMID- 9582440
TI  - Increased tyrosine phosphorylation and novel cis-acting element mediate
      activation of the fibroblast growth factor-2 (FGF-2) gene by nicotinic
      acetylcholine receptor. New mechanism for trans-synaptic regulation of cellular
      development and plasticity.
AB  - FGF-2, a mitogenic/neurotrophic protein, controls the development and plasticity
      of many types of neural cells. In neural crest-derived adrenal pheochromatocytes,
      induction of FGF-2 coincides with the establishment of functional innervation and
      is reproduced in vitro by stimulating acetylcholine receptors (AChR). The
      mechanisms by which AChR activate the FGF-2 gene were examined in cultured bovine
      adrenal medullary chromaffin (BAMC) cells in which AChR induce expression and
      nuclear accumulation of growth-promoting FGF-2 and FGF-2 receptors. Carbachol or
      nicotine increased expression of transfected FGF-2 gene promoter-luciferase
      constructs and were more potent than the muscarinic agonist ABMCB. Deletion
      analysis has identified a unique -555/-512 bp element that confers AChR
      stimulation and basal activity to the downstream FGF-2 promoter, and a separate
      protein kinase C/cAMP-responsive sequence (-625/-555 bp). Stimulation of AChR
      increased in vitro formation of protein complexes with the AChR-responsive
      element which were not displaced by target oligonucleotides for common trans
      activators. Southwestern analysis identified 50-55, 125, 140 and 170 kDa proteins
      that interact with the AChR-responsive element in a manner stimulated by AChR.
      Nicotine increased tyrosine phosphorylation of cytoplasmic and nuclear proteins,
      including 50-55 kDa promoter-binding factors. Activation of the FGF-2 promoter
      was reduced by genistein. Thus, nicotinic AChR activate the FGF-2 gene via a new
      signaling mechanism separate from the cAMP/PKC pathways. It utilizes tyrosine
      phosphorylation and interaction of trans-activating factors with a novel cis
      acting element. It offers a new pathway through which trans-synaptic signals may
      control neural development and plasticity.

PMID- 9582441
TI  - Genetic variation in functionally important domains of the bovine mtDNA control
      region.
AB  - DNA sequences of the mitochondrial control region (CR) of 32 unrelated Austrian
      cattle were analysed in order to determine the extent of variability in
      functionally important domains. Using sequencing of PCR products, allele-specific
      PCR (AS-PCR) and primer introduced restriction analysis (PIRA), 43 differences
      were observed. They included 33 transitions, five transversions, one deletion and
      four differences in the number of consecutive cytosines. Twenty-three of these
      polymorphisms have not been reported before. In addition, we analysed all
      available European cattle sequences for this region. The transcriptional start
      sites, the conserved sequence block CSB 1 and both binding sites for the
      mitochondrial transcription factor mtTFA were highly conserved. We found a
      transition in each of the inter-specifically conserved Mt4 and Mt5 elements,
      three nucleotide substitutions in the termination-associated sequence TAS-A and
      six polymorphisms in the conserved sequence block CSB 2+3, a region which has
      been implicated in mitochondrial RNA processing.

PMID- 9582442
TI  - A cis-acting regulatory element that affects the alternative splicing of a muscle
      specific exon in the mouse NCAM gene.
AB  - The pre-mRNA encoding the neural cell adhesion molecule (NCAM) is spliced to
      generate NCAM isoforms containing the muscle-specific domain (MSD) during
      myogenesis. Utilizing chimeric NCAM minigenes, we searched for cis-acting
      elements that contribute to the alternative selection of exon MSDb, one of the
      four exons encoding MSD, and identified an intronic cis-element located
      downstream of exon MSDb. The cis-element acted as a negative regulator for the
      selection of exon MSDb in nonmuscle fibroblasts but not in myoblasts, that are
      already destined to differentiate into muscle cells. The suppressive effect of
      this cis-element on the selection of exon MSDb was released in the process of
      myogenesis. When MyoD was co-expressed with a minigene containing this element in
      fibroblasts, the suppressive effect of the cis-element was released as the cells
      underwent differentiation. We propose that this cis-element contributes at least
      as one of the regulatory elements in the differentiation state-dependent
      selection of MSD exons in vivo.

PMID- 9582443
TI  - Excitotoxic injury induces monocyte chemoattractant protein-1 expression in
      neonatal rat brain.
AB  - Intra-hippocampal injection of NMDA (12.5 nmol) in postnatal day 7 (P7) rats
      results in neuronal necrosis and hippocampal atrophy; injury extends into the
      adjacent striatum, thalamus and cortex. NMDA-induced injury is marked by an acute
      microglial/monocyte response; the molecular signals that control this response
      and the role of activated microglia/monocytes in the progression of excitotoxic
      injury are unknown. Monocyte chemoattractant protein-1 (MCP-1) is a well
      characterized chemokine that regulates monocyte chemotaxis and activation, and
      contributes to the pathogenesis of monocyte-dependent tissue injury in several
      disease models. We hypothesized that MCP-1 could be a regulator of the
      microglial/monocyte response to excitotoxic injury in neonatal rat brain. To
      determine if intra-hippocampal NMDA injections induced MCP-1 mRNA expression, in
      situ hybridization assays were performed in brain samples obtained from 7-day-old
      rats, evaluated 0-24 h after intra-hippocampal NMDA injection. MCP-1 mRNA
      expression was first detected at 2 h after lesioning, in the choroid fissure,
      adjacent to the lesioned hippocampus; levels of expression increased markedly in
      the lesioned hippocampus and adjacent structures within the first 16 h after NMDA
      injection, and then rapidly declined. In control animals that received intra
      hippocampal saline injections, only minimal MCP-1 mRNA was detected, along the
      injection track. These results demonstrate that excitotoxic injury transiently
      induces MCP-1 gene expression in neonatal rat brain. The functional role of MCP-1
      in the injured brain remains to be determined.

PMID- 9582444
TI  - Enhanced expression of 14-3-3 family members in injured motoneurons.
AB  - An increase in 14-3-3 mRNA expression after hypoglossal nerve injury was
      demonstrated by RNA finger printing using the arbitrary primed polymerase chain
      reaction (RAP-PCR). RAP-PCR was carried out to compare differences in mRNA
      expression between axotomized (6 h after the transection) and normal hypoglossal
      nuclei in mice. The expression of several gene fragments was increased after
      nerve injury; one fragment was identified as 14-3-3 which is an activator of Raf
      1. Since a family of 14-3-3 genes are identified in the rat, we examined the
      expression of five members of the rat 14-3-3 family after injury (beta, gamma,
      zeta, eta and theta). Among these family members, a substantial up-regulation in
      mRNA expression was observed for the zeta and &theta; forms. Subsequent emulsion
      autoradiography of hybridization tissue sections revealed an increase in zeta and
      theta mRNA in injured motoneurons. Since 14-3-3 has the ability to dimerize and
      activate Raf-1, the up-regulation of 14-3-3 expression would be expected to
      facilitate the Ras-Erk signal pathway by Raf-1 activation. Our previous results
      have demonstrated that Shc, Erk1 and Mek1 mRNAs are up-regulated during nerve
      regeneration, whereas PKA which inhibits the Ras-Erk pathway via Raf-1 was down
      regulated. Taken together, the present results suggest that enhancement in
      expression of molecules involved in the Ras-Erk signaling is required for
      peripheral nerve regeneration.

PMID- 9582445
TI  - Dielectric studies of chain melting and denaturation in native DNA.
AB  - Dielectric methods, based on time domain reflectometry (TDR), have been employed
      to characterise DNA chain melting and denaturation. A dielectric dispersion has
      been identified, centred in the low megahertz region, which has been attributed
      to the fluctuation of counterions along short segments of the DNA chain. Chain
      melting studies have shown that the magnitude of this dispersion is dependent not
      only on the relative proportions of single to double stranded DNA but also on the
      intermolecular interactions between the DNA chains.

PMID- 9582446
TI  - Identification of a thyroid hormone response element in the promoter region of
      the rat lipocalin-type prostaglandin D synthase (beta-trace) gene.
AB  - We have previously reported that mRNA levels for the rat lipocalin-type
      prostaglandin (PG) D synthase/beta-trace (PGDS) gene, the enzyme responsible for
      the production of PGD2 in the central nervous system, are regulated by thyroid
      hormone in vivo. In this study, we describe the identification of a thyroid
      hormone (T3) response element (T3RE) in the 5'-flanking region of the rat PGDS
      gene. By radioimmunoprecipitation of genomic fragments using thyroid hormone
      receptor (TR) protein and specific anti-TR antibodies, gel-shift, foot-printing,
      mutational analysis, and transactivation assays we have identified a spaced four
      imperfect direct repeat (DR4) element, GGTTCACTTCAGGGTA (positions -586/-571),
      which functions as a T3RE when fused to a heterologous promoter. Our results
      suggest that thyroid hormone regulates the expression of the rat lipocalin-type
      PGDS gene through this element. Remarkably, the element identified also confers
      regulation by retinoic acid. Giving the important roles proposed for the PGDS
      enzyme and its product, PGD2, the major PG in the mammalian brain, the altered
      expression of the PGDS gene may contribute to the deleterious effects of
      hypothyroidism in the central nervous system.

PMID- 9582447
TI  - U14snoRNAs of the fern, Asplenium nidus, contain large sequence insertions
      compared with those of higher plants.
AB  - Northern analyses of U14snoRNAs in different plant species showed the expected
      hybridising band of approximately 120 nt in monocotyledonous and dicotyledonous
      angiosperms. In the lower plant, Bird's nest fern (Asplenium nidus), U14s were
      larger and three hybridising RNAs of approximately 190, 210 and 250 nt were
      observed. RT-PCR cloning of all three size variants using primers to the
      conserved 5' and 3' ends of higher plant U14snoRNAs showed large insertions in
      one of the plant-specific regions corresponding in position to the yeast U14
      specific Y-domain. The insertions are pyrimidine-rich in their 5' halves and
      purine-rich in their 3' halves and are likely to be sequestered in stem
      structures consistent with the proposed model of U14snoRNA secondary structure.
      The 5' flanking regions of one of the fern U14 variants was generated by PCR and
      lacked classical plant snRNA promoter elements.

PMID- 9582448
TI  - Complex alterations in gene expression occur in the knee ligaments of the
      skeletally mature multiparous rabbit during pregnancy.
AB  - Pregnancy is known to influence the function of ligaments of the knee in both
      humans and rabbits. During pregnancy, ligament laxity increases. The mechanism by
      which these changes in ligament function occur is unknown. The present study was
      undertaken to assess changes in the pattern of gene expression for a number of
      molecules which could be involved in the alterations in tissue function. Using
      RNA isolated from pregnant and age-matched nonpregnant rabbits, levels of mRNA
      for matrix molecules, proteinases and inhibitors, cytokines and growth factors
      and inducible nitric oxide synthase were assessed by semi-quantitative RT-PCR.
      The results indicate that the pregnancy-induced changes in the pattern of gene
      expression is very complex and differences in the changes observed for the medial
      collateral ligament and the anterior cruciate ligament may also indicate that
      ligament-specific effects of pregnancy occur. mRNA levels of some molecules were
      significantly elevated or suppressed, while others were unchanged, indicating
      that the changes observed were specific rather than general. While the extent of
      the molecules assessed was designed to be representative rather than exhaustive,
      the results indicate that there is likely no simple cause and effect relationship
      between the observed mechanical alterations during pregnancy and alterations in
      gene expression in the affected ligaments.

PMID- 9582450
TI  - Nitric oxide differentially affects the exocytotic and the carrier-mediated
      release of [3H] gamma-aminobutyric acid in rat hippocampal synaptosomes.
AB  - We studied the effects of nitric oxide (NO) on the Ca2+-dependent KCl-evoked
      release of gamma-aminobutyric acid (GABA) by rat hippocampal synaptosomes,
      measured in the presence of 1-(2-(((diphenyl-methylene)amino)oxy)ethyl)-1,2,5, 6
      tetrahydro-3-pyridine-carboxylic acid (NNC-711), which blocks the GABA carrier.
      Under these conditions, the NO donor, hydroxylamine, up to 1 mM, inhibited the
      Ca2+-dependent exocytotic GABA release, but did not affect the basal release.
      However, in the absence of NNC-711, hydroxylamine concentrations higher than 30
      microM caused a two-fold increase in the basal release of GABA, and the KCl
      evoked release of GABA was higher than in the presence of NNC-711 because both
      exocytotic and carrier-mediated release occur. Thus, it is expected that when
      both release mechanisms are operative, NO inhibits the exocytotic release and
      stimulates the carrier-mediated release, and the overall effect is an increased
      liberation of the neurotransmitter from the nerve terminals.

PMID- 9582449
TI  - Up-regulation of GDNFR-alpha and c-ret mRNA in facial motor neurons following
      facial nerve injury in the rat.
AB  - Glial cell line-derived neurotrophic factor (GDNF), a powerful trophic factor for
      developing, and injured adult motor neurons, has recently been shown to mediate
      its physiological effects via a multi-component receptor system comprising the
      GDNFR-alpha binding protein and the c-ret receptor tyrosine kinase. Using in situ
      hybridization histochemistry this study investigated whether adult motor neurons
      express mRNAs encoding GDNFR-alpha and c-ret, and explored possible time
      dependent changes in these mRNA species following facial nerve resection and
      crush injury. Levels of mRNA for the signaling component of the GDNF receptor, c
      ret, were increased approximately 1.4-fold in the ipsilateral facial nucleus, 1
      and 3 days after unilateral facial nerve crush and resection, but returned to
      contralateral levels by 7-21 days. GDNFR-alpha mRNA was increased from 2 to 3
      fold in the facial nucleus at 1 and 3 days after facial nerve crush and to
      similar, but more sustained (up to 21 days), levels after resection. In contrast,
      GDNF mRNA was not detectable in normal or injured facial motor neurons. The
      gradual return of c-ret and GDNFR-alpha mRNAs to control levels 21 days after
      facial nerve crush, parallels the axonal regeneration process, while nerve damage
      by resection has more severe consequences compared to nerve crush, reflected by
      the prolonged time course of increased GDNFR-alpha mRNA, similar to markers such
      as the NGF-receptor, galanin and GAP-43. These findings confirm the importance of
      GDNF trophic/signaling systems after nerve injury and suggest the potential for
      broad biological and therapeutic actions of GDNF or related factors in the CNS,
      particularly on damaged motor neurons.

PMID- 9582451
TI  - Effects of transient cerebral ischemia on hsp40 mRNA levels in rat brain.
AB  - Rats were subjected to transient cerebral ischemia by four-vessel occlusion of 30
      min duration, followed by 2, 4, 8 or 24 h of recovery. Total RNA was isolated
      from the cerebral cortex and hippocampus, and reverse transcribed into cDNA.
      Hsp40 mRNA levels of samples were evaluated by quantitative PCR. Transient
      cerebral ischemia caused a marked increase in hsp40 mRNA levels to about 250% and
      500% of control in the cortex and hippocampus respectively. Since hsp40 exerts a
      critical regulatory function in the HSC70/HSP70 ATPase cycle, an ischemia-induced
      rise of hsp40 mRNA levels could mark the onset of the recovery process after
      transient ischemia. On the other hand, the inhibitory action of hsp40 on P58 (a
      protein that activates protein synthesis by blocking the interferon-induced
      double-stranded RNA-activated protein kinase PKR) implies that the rise in hsp40
      expression may equally well contribute to the post-ischemic suppression of
      protein synthesis.

PMID- 9582452
TI  - Continuous treatment with nicotine increases diazepam binding inhibitor (DBI) and
      its mRNA in the mouse brain.
AB  - Effect of chronic treatment with nicotine on DBI and its mRNA in mouse cerebral
      cortex were examined. Continuous treatment of mice with nicotine significantly
      increased DBI content and its mRNA expression, which was completely abolished by
      simultaneous administration of mecamylamine (1 mg/kg, i.p.). These results
      indicate that chronic functional interaction between nicotine and nicotinic
      acetylcholine receptors has a critical role in increases in DBI content and its
      mRNA expression.

PMID- 9582453
TI  - Acute administration of cocaine, but not amphetamine, increases the level of
      synaptotagmin IV mRNA in the dorsal striatum of rat.
AB  - Synaptotagmin IV (Syt IV) is an inducible member of a multi-gene family of
      synaptic vesicle proteins that participate in Ca2+-dependent and Ca2+-independent
      interactions during membrane trafficking. We have examined the pattern of
      expression of Syt IV mRNA following the administration of cocaine and
      amphetamine. A single acute dose of cocaine, but not amphetamine, resulted in a
      transient increase, as determined by in situ hybridization, in the steady-state
      level of Syt IV mRNA in the dorsal striatum of rats 1 h after the administration
      of the drug. No change in the hybridization pattern of the Syt IV-specific probe
      to other regions of the rat brain were observed following cocaine or amphetamine
      administration at the time points examined (1, 3, 6, 12 and 24 h). The pattern of
      synaptotagmin I-(Syt I) specific hybridization remained constant, relative to
      controls, for both the cocaine- and amphetamine-treated animals. Northern
      hybridization analysis of mRNA isolated from striatal tissue using
      oligonucleotide probes specific to Syt I and Syt IV demonstrated that the probes
      hybridized exclusively to transcripts of the sizes previously reported for these
      two synaptotagmins and confirmed that the relative level of Syt IV to Syt I mRNA
      increased following the administration of cocaine but not amphetamine. These
      results indicate that these drugs have different effects on altering the levels
      of Syt IV mRNA. This work, in conjunction with earlier work that demonstrated
      that cocaine and amphetamine have different effects on the expression of
      immediate early genes such as c-Fos, supports the hypothesis that these
      psychotropic agents evoke different patterns of gene expression which may lead to
      alteration in synaptic efficacy.

PMID- 9582454
TI  - The secretory epithelial cells of the choroid plexus employ a novel kinesin
      related protein 

PMID- 9582455
TI  - HIV therapy guidelines.

PMID- 9582456
TI  - Randomised trials of STD treatment for HIV prevention: report of an international
      workshop. HIV/STD Trials Workshop Group.
AB  - Three community trials of the impact of STD treatment interventions on HIV
      incidence in rural populations have been completed or are in progress in Uganda
      and Tanzania. Investigators from these trials met for a joint technical workshop
      in Baltimore in May 1996. This report summarises the consensus of the workshop,
      with the aim of providing useful input to research on HIV intervention
      strategies. Issues discussed include: (i) the role of community randomised
      trials; (ii) strategies for STD management; (iii) epidemiological and statistical
      issues in the design and analysis of community randomised trials; (iv) diagnostic
      methods for STDs in population surveys; (v) treatment regimens for STDs in rural
      Africa; and (vi) ethical issues in community trials.

PMID- 9582457
TI  - Voluntary confidential HIV testing of STD patients in Switzerland, 1990-5: HIV
      test refusers cause different biases on HIV prevalences in heterosexuals and
      homo/bisexuals. Swiss Network of Dermatovenereology Policlinics.
AB  - OBJECTIVES: To monitor the prevalence of HIV infection among heterosexual and
      male homo/bisexual STD patients and assess the effect of HIV test refusers on the
      HIV prevalences. METHODS: A voluntary confidential HIV test was offered to all
      people diagnosed with an STD at the Swiss Network of Dermatovenerology
      Policlinics (SNDP) between July 1990 and June 1995. Anonymous sociodemographic
      and behavioural information was collected for each patient regardless of whether
      s/he accepted or refused the HIV test. RESULTS: The prevalence of HIV was 1.6%
      among heterosexuals and 22.4% homo/bisexual men and remained stable between July
      1990 and June 1995. Refusal rates were 17.5% among heterosexuals and 16.0% among
      homo/bisexual men and did not change significantly over time. To assess the
      potential effect of HIV test refusers on the monitored HIV prevalences, we
      analysed test refusers by multivariate logistic regression. Among heterosexuals,
      refusal rates were significantly higher among patients with relatively low risk
      behaviours (patients reporting 0-1 sexual partners in the previous 6 months)
      while among homo/bisexual men they were significantly higher in those with high
      risk behaviours (patients reporting 10 or more sexual partners in the previous 6
      months). CONCLUSIONS: We found high and stable HIV prevalences among patients
      treated for an STD at the SNDP. It appears that HIV test refusers biased HIV
      prevalences among heterosexuals and homo/bisexual men in different directions: in
      heterosexuals HIV prevalences were overestimated and in homo/bisexuals they were
      underestimated. A regular analysis of the characteristics of HIV test refusers
      should be an integral part of surveillance systems which use voluntary
      confidential HIV testing.

PMID- 9582458
TI  - Sexual behaviour of adolescents before and after the advent of AIDS.
AB  - OBJECTIVES: To asses changes in sexual behaviour and use of contraceptive methods
      in Danish adolescents from the period before the advent of AIDS up to the
      present. DESIGN: Comparative study comparing data obtained from two identical
      cross sectional surveys SETTING: Grenaa Gymnasium, Denmark. SUBJECTS: 626 high
      school students in 1982 and 499 high school students in 1996. METHODS: An
      anonymous standardised self administered questionnaire handed out to high school
      students at Grenaa Gymnasium in spring 1982. In spring 1996 an identical
      questionnaire was handed out to every high school student at the same gymnasium.
      MAIN OUTCOME MEASURES: Age at first sexual intercourse, contraceptive use, and
      reasons for choice of contraceptive strategy. RESULTS: Today more males had
      experienced the first sexual intercourse before their 16th birthday (p = 0.047)
      compared with 1982, the reverse held for females (p = 0.003). From 1982 to 1996
      condom use increased in males with no regular partner (p = 0.009). In females
      with no regular partner, there was during the same period an increase in
      considering the condom a personal contraceptive method (p = 0.017). In 1982 and
      1996 protection from sexually transmitted diseases was given as reason for the
      choice of contraceptive strategy by 21% and 72% of males with no regular partner
      (p < 0.001), and by 7% and 32% of males with a regular partner (p < 0.001). The
      corresponding figures for females in 1982 and 1996 were 10% and 71% (p < 0.001)
      for those with no regular partner and 4% and 21% (p < 0.001) for those with a
      regular partner. CONCLUSION: Condom use has increased among adolescents with no
      regular partner brought up under the widespread awareness of AIDS, and the reason
      for this is to be protected from sexually transmitted diseases. A future decline
      in the incidence of various sexually transmitted diseases may be expected, and
      information on safe sexual practices should be continued.

PMID- 9582459
TI  - Provision for sexual health care of adolescents in genitourinary medicine clinics
      in the United Kingdom. The British Cooperative Clinical Group.
AB  - OBJECTIVES: To investigate the provision for sexual health care of adolescents in
      genitourinary medicine clinics in the United Kingdom. METHODS: A questionnaire
      was sent to all 170 consultants in charge of genitourinary medicine clinics in
      the United Kingdom. RESULTS: Completed questionnaires were received from 119
      consultants in charge of clinics. Eleven per cent of attenders during April-June
      1995 were aged under 20 years. Attenders aged under 16 years and from 16-19 years
      old were found to have significantly higher rated of gonorrhoea than those aged
      over 19. The same applied to male attenders with chlamydia. Female attenders aged
      16-19 had significantly higher rates of anogenital warts than those aged over 19.
      Thirty six per cent of female cases of gonorrhoea occurred under the age of 20
      years. In most clinics (74%) it was policy for a new clinic attender aged under
      16 years to see a health adviser. Most clinics (79%) provided emergency
      contraception, but few (14%) had a full contraception service. Most clinics
      participated in STD/HIV/sexual health education in the local community,
      especially in schools (74%) and colleges (70%). Seventy five per cent of health
      authorities had medical services designated for young people, but only 18% had
      such services which offered screening for STDs. Only 4% of genitourinary medicine
      clinics held sessions which were designated for young people (upper age limit 21
      years or less). CONCLUSIONS: Genitourinary medicine clinics in the United Kingdom
      provide a range of services, including extensive education in the community, to
      promote sexual health among adolescents. A critical evaluation of the quality of
      health education activity by genitourinary medicine clinics would be of interest.

PMID- 9582461
TI  - Necrotising herpetic retinopathy in patients with advance HIV disease.
AB  - OBJECTIVES: To describe the presenting features, clinical and laboratory
      diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy
      (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory
      data review of five HIV infected patients presenting to the specialist HIV/AIDS
      unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical
      diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median
      CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus
      (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual
      acuity; one also had headache and another ocular pain. All had typical retinal
      appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in
      vitreous fluid of one of the four) and in vitreous fluid of one other. One
      patient refused therapy and rapidly became blind. Four patients received
      intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently
      received oral famciclovir and one oral valaciclovir; two patients also had
      intravitreal injections of foscarnet. In none of the four did treatment bring
      about improvement in visual acuity, but in all four visual loss from retinitis
      was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV
      disease and is strongly associated with evidence of VZV infection. With
      aggressive use of antiviral drugs the outcome is not uniformly poor.

PMID- 9582460
TI  - Behavioural and demographic characteristics of attenders at two genitourinary
      medicine clinics in England.
AB  - OBJECTIVES: To investigate how attenders with sexually transmitted disease (STD)
      differ from the general population with respect to sexual behaviour, and to
      identify which attenders at genitourinary medicine (GUM) clinics are at
      particular behavioural risk for acquiring STD. DESIGN: Multicentre cross
      sectional survey. SETTING: Two genitourinary medicine clinics, one in London and
      one in Sheffield SUBJECTS: 20,516 patients attending the two clinics over an 18
      month period. MAIN OUTCOME MEASURES: Behavioural and demographic characteristics
      and clinical diagnoses were recorded for each patient. RESULTS: 8862 patients, in
      whom 12,506 diagnoses were made, were seen in the Sheffield clinic, and 11,654
      patients, in whom 20,243 diagnoses were made, were seen in the London clinic.
      When compared with the reported results from a general population survey, there
      were higher proportions of clinic attenders reporting two or more sexual partners
      in the preceding 12 months (p < 0.001), and a higher proportion of males
      reporting homosexual contact (13% compared with 1%, p < 0.001). Only age and
      number of sexual partners in the past 12 months were significantly associated
      with acute STDs for each sex in each clinic. Acute STDs tended to occur with
      greater frequency in the younger age groups, peaking among 16-19 year olds,
      particularly among females. CONCLUSIONS: The results have confirmed that patients
      with STDs exhibit higher risk sexual behaviour than the general population, and
      have highlighted the problem of continuing high risk behaviour among younger
      attenders, particularly younger homosexual men. This study has demonstrated that
      among GUM clinic attenders age and number of sexual partners are key risk factors
      for the acquisition of an acute STD. The results of this survey also indicate,
      however, that half of the females and more than one quarter of males with acute
      STDs reported only one sexual partner in the past 12 months, suggesting that
      health education messages should point out that it is not only those who have
      multiple recent sexual partners, or who have recently changed sexual partner,
      that are at risk of STD, including HIV.

PMID- 9582462
TI  - Herpes zoster and the stage and prognosis of HIV-1 infection.
AB  - OBJECTIVES: To examine the incidence of herpes zoster in HIV-1 infection. To
      assess the prognostic significance of the occurrence of herpes zoster and
      progression to AIDS or death DESIGN AND METHODS: 146 homosexually active men with
      known times of HIV-1 seroconversion were identified through the Sydney AIDS
      Prospective Study and the clinic records of a private medical practice with large
      caseload of HIV infected homosexual men. Medical records were reviewed for a
      history of herpes zoster, CD4+ lymphocyte counts, and HIV-1 disease status. Cox's
      proportional hazards model was used to determine whether herpes zoster predicted
      progression to AIDS or death. RESULTS: After a mean follow up of 54 months, 30
      men (20%) had an episode of herpes zoster and three of these men had one
      recurrence. The overall incidence of herpes zoster was 44.4 episodes per 1000
      person years (95% CI 30.0-63.5). Herpes zoster was not found to be a marker of
      deteriorating immune functions as measured by CD4+ lymphocyte counts. CD4+ counts
      did not differ significantly between those with and without zoster at 1 year (551
      v 572.10(6)/1, p = 0.79), 2 years (451 v 557, p = 0.11), and 3 years (424 v 481,
      p = 0.50) following HIV-1 seroconversion. There was no statistically significant
      difference in progression to AIDS (RR = 1.89, 95% CI 0.80-4.46, p = 0.15) or
      death (RR = 0.90, 95% CI 0.31-2.65, p = 0.85) from HIV-1 sero-conversion in those
      who did and those who did not develop herpes zoster. CONCLUSION: The incidence of
      herpes zoster was consistent with the findings of other studies. There was no
      association between the occurrence of herpes zoster and progression of HIV-1
      disease.

PMID- 9582463
TI  - Prior fluconazole exposure as an independent risk factor for fluconazole
      resistant candidosis in HIV positive patients: a case-control study.
AB  - OBJECTIVES: To determine if prior fluconazole exposure was an independent risk
      factor for fluconazole resistant candidosis in HIV positive patients. METHODS:
      Twenty five HIV positive cases with fluconazole resistant oral candidosis were
      matched by CD4 lymphocyte count and time since first episode of candidosis to 25
      HIV positive controls with susceptible candidosis. For each individual a history
      of prior azole prophylaxis was compiled from computerised pharmacy records and
      review of case notes. RESULTS: The total days of prior azole therapy prescribed
      was significantly greater for cases than controls. These differences were
      attributable to prescriptions for secondary prophylaxis against recurrent
      candidosis, the cases having received significantly longer continuous azole
      prophylaxis than controls, with no difference in days of prior azole therapy
      remaining between the two groups if prophylactic prescriptions were excluded. The
      total cumulative dose of fluconazole received was significantly higher for cases
      than controls, though mean daily fluconazole doses did not differ significantly
      between the two groups. CONCLUSION: Even after controlling for degree of
      immunosuppression and duration of recurrent candidosis, the association between
      prior azole exposure and fluconazole resistant candidosis remains significant and
      largely reflects differences in the prescription of secondary antifungal
      prophylaxis.

PMID- 9582464
TI  - Women with recurrent vaginal candidosis have normal peripheral blood B and T
      lymphocyte subset levels.
AB  - OBJECTIVE: To compare the B and T lymphocyte subset levels of otherwise healthy
      women suffering from frequently recurrent vaginal candidosis with a healthy
      control group. SUBJECTS: 26 unselected otherwise healthy women of reproductive
      age with at least four attacks of vaginal candidosis in the past year and more
      than three vaginal isolates of a moderate or heavy growth of Candida albicans.
      Controls were 26 patients or clinical and laboratory staff (asymptomatic for
      genital infection) matched for time of day and age within 5 years. Only three
      patients accepted an HIV test. All proved HIV negative. No controls were tested.
      MAIN OUTCOME MEASURES: T lymphocyte subsets (CD4 and 8) and B lymphocytes (CD 19)
      as estimated from the total lymphocyte count and flow cytometry. RESULTS: No
      statistically significant difference between patients and controls. CONCLUSION:
      No significant difference was found between patients and controls in levels of
      lymphocyte subsets.

PMID- 9582465
TI  - Nasopharyngeal flora in HIV seropositive men who have sex with men.
AB  - OBJECTIVES: To assess, in men who were infected with the human immunodeficiency
      virus (HIV) and who identified themselves as having had sex with men; the
      nasopharyngeal prevalence of Neisseria gonorrhoeae, N meningitidis,
      Corynebacterium diphtheriae, and candida species; oral sexual behaviour; the
      relation between oral flora and oral sexual behavior. METHOD: Nasopharyngeal
      swabs were taken from HIV seropositive men for culture. The men were also asked
      to complete a self administered questionnaire. RESULTS: 390 men were recruited;
      286 (73.3%) provided nasopharyngeal samples and questionnaires; 41 (10.5%)
      provided nasopharyngeal samples only; 63 (16.2%) provided questionnaires only.
      From the 327 nasopharyngeal samples N meningitidis was cultured in 49 (15%) and
      candida species in 165 (50.5%). Cultures for N gonorrhoeae and C diphtheriae were
      all negative. Data from the 349 completed questionnaires indicated that 285 men
      were practising oro-penile sex, over 90% did not consistently use condoms; 150
      men were practising oro-anal sex, one used dental dams. In those providing both
      nasopharyngeal samples and sexual behaviour data meningococcal carriage was
      identified in 40 (17.5%) of the 228 men practising receptive oro-penile sex,
      compared with one (2.3%) of the 43 non-practisers (p < 0.025); in 21 (20%) of the
      105 men practising insertive oro-anal sex, compared with 17 (12.5%) of the 136
      non-practisers (p = 0.12). No correlation was identified between yeast carriage
      and oro-genital sex. CONCLUSION: Oro-genital sex, usually without barrier
      protection, is common among HIV infected men who have sex with men. It appears to
      be associated with increased meningococcal carriage but is autonomous to candida
      species isolation. Routine screening for nasopharyngeal N gonorrhoeae is not
      deemed necessary.

PMID- 9582467
TI  - Prevalence and risk factors for hepatitis B virus infections among visitors to an
      STD clinic.
AB  - OBJECTIVE: To determine the prevalence and risk factors for hepatitis B virus
      (HBV) infections among individuals attending an STD clinic in a low endemic
      region. STUDY DESIGN: A total of 1228 women and 1648 men attending the STD clinic
      at the University Hospital Rotterdam, Netherlands, were examined for HBV
      infection by determination of hepatitis B surface antigen (HBsAg) and antibodies
      to hepatitis B core antigen (anti-HBc). Demographic characteristics, information
      on sexual behaviour, and intravenous drug use were recorded. RESULTS: The
      seroprevalence of HBsAg was 1.4% in women and 2.1% in men (0% in homosexual men).
      The seroprevalence of anti-HBc was 13% in women and 20% in men (36% in homosexual
      men). Native country, intravenous drug use, a history of STD, and the number of
      partners in the past half year (inversely) were independent risk factors for
      HBsAg positivity in women and heterosexual men. For anti-HBc independent
      associations were observed for native country, age, intravenous drug use,
      commercial sex, number of lifetime partners, homosexual contacts, orogenital
      contact (inverse), and a history of STD. CONCLUSION: The HBV prevalence in the
      STD clinic attendants was high, exceeding the national estimate, and indicates
      that the STD clinic population may be considered a high risk group. Our data
      confirmed an increased risk for HBV infections among established risk groups.
      Therefore, these risk groups should be routinely screened to identify HBV cases
      for counselling and contact tracing.

PMID- 9582466
TI  - Development of intralesional therapy with fluorouracil/adrenaline injectable gel
      for management of condylomata acuminata: two phase II clinical studies.
AB  - OBJECTIVES: To evaluate a sustained release chemotherapy for treating condylomata
      acuminata with an injectable gel containing fluorouracil and adrenaline (5
      FU/adrenaline gel). Study 1-- To assess contributions of the components of 5
      FU/adrenaline gel to efficacy. Study 2--To assess therapeutic contribution of
      adrenaline and safety and efficacy of the formulations. DESIGN: Randomised,
      double blind, placebo controlled studies. SETTING: Private practices and
      university clinics in the United States. PATIENTS: Men and women with new,
      recurrent, or refractory external condylomata acuminata. INTERVENTION: Six
      injections over 8 weeks; follow up visits at weeks 1, 4, 8, and 12. MAIN OUTCOME
      MEASURES:  EFFICACY: patient/wart response, times to complete response,
      recurrence rates. SAFETY: injection reactions, tissue conditions, other adverse
      events, laboratory studies. RESULTS: Study 1: 132 evaluable patients. Complete
      response (CR) rate was highest for the 5-FU/adrenaline gel group, followed by the
      5-FU/adrenaline solution group, then the 5-FU gel group. 5-FU, adrenaline, and
      the collagen gel vehicle (in the presence of 5-FU) significantly affected CR and
      strongly influenced time to CR. The effects of 5-FU and adrenaline were
      statistically significant. Cutaneous reactions were mild to moderate. Study 2:
      187 evaluable patients. Patients treated with 5-FU/adrenaline gel had a
      significantly higher CR rate and lower cumulative 90 day recurrence rate than
      those treated with 5-FU gel without adrenaline. Treatments were generally well
      tolerated, with only three treatment related, serious adverse events. CONCLUSION:
      5-FU/adrenaline gel is safe and efficacious for treatment of condylomata
      acuminata, and when compared with individual or various combinations of
      components, this formulation provided the greatest therapeutic advantage.

PMID- 9582468
TI  - PCR for detection of Chlamydia trachomatis in endocervical, urethral, rectal, and
      pharyngeal swab samples obtained from patients attending an STD clinic.
AB  - OBJECTIVE: To investigate, by use of the Amplicor PCR in a routine setting, the
      recovery rate of Chlamydia trachomatis in ano-rectal and pharyngeal swab samples
      obtained from males and females attending an STD clinic in relation to sexual
      practices, symptoms, and signs. DESIGN: Data regarding sexual practices, and
      symptoms and signs related to the rectum and pharynx, were obtained from 196
      females and 208 males, including 31 homosexuals and eight bisexuals. Swab samples
      were obtained from the urethra, rectum, and pharynx from all the patients. An
      additional endocervical swab sample was obtained from the females. METHODS: All
      samples were analysed by the Amplicor PCR (Roche). SETTING: Rudolph Bergh's
      Hospital, a clinic for sexually transmitted diseases situated in the centre of
      Copenhagen, Denmark. RESULTS: The overall prevalence of urogenital C trachomatis
      infection was 9.2% (37/404). The specificity of the Amplicor PCR was 100% for
      both ano-rectal and pharyngeal swab samples. In females three (13%) of the 23
      infections were detected only by testing an ano-rectal or throat swab sample. In
      homosexual males two (67%) of three infections were detected only by the
      anorectal swab sample. Ano-rectal intercourse without use of condom was reported
      by 44% of females and by 52% of homosexual males. Fellatio without condom use was
      reported by 91% of females, and 80% of heterosexual males practised cunnilingus.
      Pharyngeal infection, however, occurred only in females, and the presence of
      pharyngeal symptoms or signs seemed predictive for pharyngeal C trachomatis
      infection, for which the time of incubation or colonisation exceeded 3 months.
      The presence of ano-rectal signs or symptoms was not predictive for an ano-rectal
      C trachomatis infection. CONCLUSION: The Amplicor PCR can be used on ano-rectal
      and pharyngeal swab samples. Ano-rectal swab samples should be obtained in
      females and homosexual males at high risk of being infected. Pharyngeal samples
      should be taken in females at high risk of being infected, especially when
      pharyngeal signs or symptoms are present.

PMID- 9582469
TI  - Evaluation of the microparticle enzyme immunoassay Abbott IMx Select Chlamydia
      and the importance of urethral site sampling to detect Chlamydia trachomatis in
      women.
AB  - OBJECTIVE: To evaluate the commercial microparticle enzyme immunoassay (MEIA),
      Abbott IMx Select Chlamydia, for the detection of Chlamydia trachomatis in women
      and to compare its performance with endocervical cell culture. Also, to determine
      whether sampling the urethral site is an important part of chlamydial diagnosis
      in women. SETTING: The Auckland, Manukau, and Waitakere Sexual Health Clinics,
      Auckland, New Zealand and the Department of Clinical Microbiology, Auckland
      Hospital, Auckland, New Zealand. PATIENTS: The study population consisted of 622
      consecutive women who attended the three sexual health clinics. METHODS: The IMx
      Chlamydia assay was performed on an IMx analyser, following a specimen treatment
      procedure. All reactive samples from the IMx Chlamydia assay were confirmed using
      the IMx Chlamydia blocking antibody reagent. The Syva direct fluorescent antibody
      (DFA) test was used to aid in resolving discrepancies. The cell culture technique
      was performed in shell vials using cycloheximide treated McCoy cells, which were
      stained using a fluorescein conjugated monoclonal antibody. RESULTS: When
      compared against the endocervical cell culture, the IMx Chlamydia had a
      sensitivity of 82.1% (23/28) and a specificity of 99.3% (590/594). When compared
      against an expanded gold standard, the IMx Chlamydia and endocervical cell
      culture had sensitivities of 84.4% (27/32) and 87.5% (28/32), specificities of
      100% (590/590) and 100% (590/590), positive predictive values of 100% (27/27) and
      100% (28/28), negative predictive values of 99.2% (590/595) and 99.3% (590/594),
      and accuracies of 99.2% (617/622) and 99.4% (618/622), respectively. The
      prevalence rate by endocervical cell culture and the expanded gold standard were
      4.5% and 5.1%, respectively. Additional urethral cell culture testing revealed a
      further nine patients positive from this site only, giving a 28% (9/32) increase
      in the number of patients diagnosed for chlamydia, thus giving an overall
      prevalence of 6.6% (41/622). CONCLUSIONS: The IMx Chlamydia assay is an easy and
      rapid test to perform, it is cost effective, and shows similar performance to
      endocervical cell culture in the female population studied and is thus an
      excellent alternative to culture for the diagnosis of C trachomatis. The study
      also showed the importance of urethral site sampling in these women, as
      endocervical testing alone will underestimate the prevalence of chlamydial
      genital infection.

PMID- 9582470
TI  - Chlamydia trachomatis in hydrocele fluid.
AB  - OBJECTIVE: To determine the presence of Chlamydia trachomatis in hydrocele fluid.
      METHODS: 90 male patients with hydrocele of tunica vaginalis from an endemic area
      for bancroftian filariasis were investigated for the presence of Chlamydia
      trachomatis in their hydrocele fluids. C trachomatis antigen detection tests-a
      direct immunofluorescence assay and an enzyme immunoassay along with polymerase
      chain reaction assay for amplification of a 517 bp fragment of C trachomatis
      endogenous plasmid-were used in this study. The patients were also tested for the
      presence of microfilaria in their hydrocele fluids and night blood.
      Histopathological examination was carried out to detect adult filarial worm in
      tunica vaginalis testes. RESULTS: Eight (8.88%) patients had chlamydia antigen in
      the hydrocele fluids; C trachomatis plasmid sequences could be amplified from
      five of these. Seven (7.77%) patients had microfilaria in the hydrocele fluids,
      three of them having adult worm in tunica vaginalis. CONCLUSION: C trachomatis
      infection might be associated with hydrocele in some of these patients.

PMID- 9582471
TI  - Cefaclor, an alternative to third generation cephalosporins for the treatment of
      gonococcal urethritis in the developing world?
AB  - OBJECTIVE: To reassess the in vivo and in vitro efficacy of cefaclor for the
      treatment of uncomplicated gonococcal infection. DESIGN: Open clinical trail
      conducted in South Africa among consecutive male patients with symptoms and signs
      of uncomplicated urethritis and laboratory evidence of gonorrhoea. METHODS:
      Patients were treated with 3 g of cefaclor plus 1 g probenecid as a single dose.
      Urethral specimens were cultured for Neisseria gonorrhoeae at the initial visit
      and at follow up. Patients were considered cured if follow up cultures were
      negative. Treatment was considered to have failed in the patients infected with
      identical gonococcal strains at the initial and at the control visit. Those with
      evidence of infection at the follow up visit were administered 400 mg of
      ofloxacin and doxycycline 100 mg twice daily for 7 days. Minimal inhibitory
      concentrations (MICs) of cefaclor were determined by an agar dilution technique
      on the gonococcal isolates from the study subjects. The results were compared
      with those of isolates from three other African countries. RESULTS: Of 155
      patients evaluated, 151 were cured (97%). Thirty per cent of the patients
      complained of adverse effects, mainly gastrointestinal. Even though MICs for the
      isolates from the three other African countries were significantly higher than
      those for the isolates from the study, none was considered resistant to cefaclor
      in vitro. MICs were markedly influenced by the type of test medium used.
      CONCLUSION: The trial demonstrated the efficacy of a single oral dose of cefaclor
      with probenecid for the treatment of uncomplicated gonococcal urethritis in South
      Africa. Its potential as an alternative therapy to third generation
      cephalosporins deserves to be further investigated.

PMID- 9582473
TI  - Risk factors for gonorrhoea: case-control study.
AB  - OBJECTIVE: To define risk factors for gonococcal infection. METHODS: A case
      control study comparing 200 gonorrhoea cases with 400 patients with non
      gonococcal genitourinary infections and 400 patients with various skin diseases,
      all of them attending City Department for Skin and Venereal Diseases In Belgrade
      (Yugoslavia) from October 1993 to December 1994. RESULTS: According to
      multivariate logistic regression analysis the following factors were
      significantly related to gonorrhoea in men: education level, sexual contact same
      day as meeting, condom use, history of prior gonorrhoea, and casual and/or new
      sex partner in the past month. Age, sexual contact same day as meeting, number of
      partners in the past year, and frequency of sexual intercourse in the past month
      were independently, significantly related to gonorrhoea in women. Also, in
      females, gonorrhoea was significantly more frequent in industrial workers and
      supported people. CONCLUSION: Since sexual behaviour, low education level,
      younger ages, and low socioeconomic status were found to be related to gonococcal
      infection, health education at early age seems to be the most appropriate means
      of altering high risk behaviour.

PMID- 9582472
TI  - Surveillance of antibiotic resistance in Neisseria gonorrhoeae in The
      Netherlands, 1977-95.
AB  - OBJECTIVE: To evaluate the prevalence and epidemiology of penicillinase producing
      Neisseria gonorrhoeae (PPNG) and tetracycline resistant N gonorrhoeae (TRNG) in
      the period 1977-95 in the Netherlands. To compare auxotypes, serovars, and
      antibiograms of PPNG, non-PPNG, and TRNG. To identify determinants in patient
      characteristics for the epidemic spread of TRNG/PPNG. METHODS: With respect to
      the national gonococcal surveillance all PPNG isolates from 30 laboratories over
      the country in 1977-90 and all gonococcal isolates from five sentinel
      laboratories (during 1 month per quarter) in 1991-5 were collected. Isolates were
      auxotyped and serotyped, the susceptibility for various antibiotics was tested
      and plasmid contents were evaluated. Additional data on PPNG infected individuals
      were collected retrospectively during a microepidemic of TRNG/PPNG. Univariate
      and multivariate analyses were performed to identify risk factors for TRNG/PPNG
      infections. RESULTS: In 1995 an overall high prevalence of PPNG infection (27%)
      and TRNG among PPNG infection (24%) was found in the Netherlands. Importantly,
      PPNG were found to have higher MICs for ceftriaxone and ciprofloxacin than non
      PPNG; clinically relevant resistance to these antibiotics (or related agents) may
      emerge first among these strains. The observed diversity of strains (123
      auxo/serovar classes since 1988) indicates a continuous introduction of new
      strains into the community. The epidemic increase of TRNG/PPNG was mainly caused
      by A/S classes NR/1B-6, PRO/1A-3, and PRO/1A-6, suggesting a clonal spread of a
      few strains; the rapid spread was associated with transmission in high risk
      individuals (that is, prostitutes and their clients). CONCLUSION: The prevalence
      of PPNG in the Netherlands remains high and reduced sensitivity to other
      antimicrobials was detected among the PPNG strains. This underlines the necessity
      for a continuous national surveillance of resistance in gonococci including
      limited epidemiological information.

PMID- 9582475
TI  - Diagnosis of neurosyphilis: appraisal of clinical caseload.
AB  - OBJECTIVES: To review the management of a cohort of patients with positive
      treponemal serology and psychiatric and/or neurological disorders. METHODS: A
      retrospective case note review of 172 patients with positive treponemal serology
      attending the Patrick Clement's Clinic, Central Middlesex Hospital between
      December 1990 and November 1995 was performed. RESULTS: 101 men and 71 women were
      new attenders diagnosed with positive treponemal serology. A neurological problem
      was identified in 27 patients (12 women and 15 men) with psychiatric and/or
      neurological disorders, of whom 20 (six women and 14 men) underwent investigation
      of the cerebrospinal fluid (CSF). With the medical history and results of CSF-RPR
      and FTA tests, white cell count (WCC), and total protein level in the CSF, 10
      patients (eight men and two women) were diagnosed with likely neurosyphilis and
      17 with neurological disorders not thought to be caused by syphilis. The clinical
      features in those having neurosyphilis were sensorineural hearing loss (n = 5)
      and tabes dorsalis (n = 5). In the seven patients diagnosed with neurosyphilis
      who underwent CSF examination one patient had a reactive CSF-FTA, elevated
      protein, and elevated WCC; one patient had a reactive CSF-FTA and RPR with
      elevated protein; the total protein only was elevated in three cases and the WCC
      elevated in one case. Nine of the 10 patients with neurosyphilis received
      adequate neurosyphilitic treatment; one patient was lost to follow up.
      CONCLUSIONS: The management of patients with positive treponemal serology and
      psychiatric and/or neurological disorders was consistent. Patients with suspected
      neurosyphilis or patients with neurological signs compatible with neurosyphilis
      (who did not undergo CSF examination) were treated with adequate neurosyphilitic
      therapy.

PMID- 9582474
TI  - Serological markers for treponemal infection in children in rural Kilimanjaro,
      Tanzania: evidence of syphilis or non-venereal treponematoses?
AB  - OBJECTIVE: To determine the seroprevalence of treponemal infection and possible
      risk factors among children aged 0-14 in the general population of a rural
      Tanzanian village. METHODS: The survey was conducted as a part of a cross section
      study of a total village population on HIV and sexually transmitted disease.
      Among 1708 registered children aged 0-14, the 553 first attending were tested for
      treponemal infection with both rapid plasma reagin test (RPR) and Treponema
      pallidum Haemagglutination test (TPHA). These children belonged to a household
      cohort--also including their parents, siblings, and other household members--with
      1339 members; 1224 (91.4% participated in the survey and 82.1% of these were
      tested for treponemal infection. RESULTS: The overall prevalence for the TPHA
      test was 6.4% among girls and 1.1% among boys (odds ratio, OR = 6.5; 95%
      confidence interval, CI: 1.9-22.3). The sex difference was most pronounced in the
      age group 10-14; 11.1% among girls versus 1.0% among boys (OR = 12.8; CI: 1.6
      101.9). Among the 20 children who were TPHA positive, we found two cases of
      active, congenital syphilis. There was a lack of association between positive
      serology in children and positive serology in their parents. CONCLUSION: The
      highly significant predominance of girls testing positive for TPHA, and the
      concomitant lack of association between parents' and children's serostatus might
      point to sexual transmission as being the most common route of transmission of
      treponemal infection in girls during childhood in this village. The sources of
      infection for the seropositive girls are possibly found outside the family.

PMID- 9582476
TI  - Sexually transmissible diseases--knowledge and practices of general practitioners
      in Victoria, Australia.
AB  - OBJECTIVE: To examine knowledge and practices in relation to sexually
      transmissible diseases (STDs) of general practitioners (GPs) in Victoria,
      Australia. METHOD: A questionnaire was distributed to 520 Victorian GPs randomly
      selected from the Australian Medical Publishing Company (AMPCo) database of
      Australian medical practitioners. RESULTS: A response rate of 85% was obtained.
      While sexual health consultations were common for Victorian GPs, STD caseloads
      were generally low. Knowledge of clinical features of symptomatic STDs and of
      important STD epidemiology was generally good although there was a lower
      awareness of the asymptomatic nature of the most prevalent STDs in Victoria.
      Diagnostic tests were generally selected appropriately although many GPs did not
      perform the gold standard combination of tests required for adequate differential
      diagnosis. Level of STD STD knowledge was related to frequency of advising about
      safe sex, diagnosing STDs, and younger practitioner age. Attendance at any of a
      number of postgraduate courses of relevance to the management of STDs was not
      related to better STD knowledge overall. CONCLUSIONS: Prevention and detection of
      STDs in general practice involve risk assessment and screening of asymptomatic
      patients as well as effective treatment of symptomatic patients and their
      contacts. Results presented here suggest that GPs have good knowledge and use
      appropriate investigations for patients presenting with symptoms of an STD. The
      low levels of awareness of the asymptomatic nature of many STDs and other
      particular aspects of STD knowledge and practice should be addressed in
      undergraduate and postgraduate medical education programmes.

PMID- 9582477
TI  - Utilisation of genitourinary medicine services by general practitioners: effect
      of geographic location, fundholding status, and potential effect of total
      fundholding.
AB  - OBJECTIVES: To determine the current utilisation of genitourinary medicine (GUM)
      services by general practitioners (GPs) and any changes likely to occur with
      moves towards a primary care led NHS. METHODS: A questionnaire survey of
      practising GPs appearing in the Medical Directory in England and Wales to
      determine the effect of geographical location, fundholding status, and potential
      effect of total fundholding on referrals to GUM clinics. RESULTS: Referral
      patterns for STDs varied according to the genital infection concerned, being
      highest for gonorrhoea and lowest for Trichomonas vaginalis infection. Referral
      patterns were little affected by geographic location of the practice or
      fundholding status. The reported intention on becoming total fundholding was a
      modest shift towards more STDs being treated in the community which varied
      according to the genital infection concerned. CONCLUSIONS: Although some GPs
      elect to always treat some STDs in the community most refer patients to GUM
      clinics. There appears to be little enthusiasm among GPs, should they become
      total fundholders, to extend their range of services to include STD provision.

PMID- 9582478
TI  - Psychological and psychosexual aspects of vulvar vestibulitis.
AB  - AIMS: To objectively assess the psychological and psychosexual morbidity of
      patients with vulvar vestibulitis. METHODS: 30 patients with variable degrees of
      vulvar vestibulitis were recruited from a vulval clinic. Each patient underwent a
      detailed history and clinical examination. Friedrich's criteria were used for the
      diagnosis of vulvar vestibulitis. Standardised questionnaires to assess
      psychological and psychosexual function were completed by the patient before
      review. These questionnaires were the STAI and a modified psychosexual
      questionnaire introduced by Campion. RESULTS: Patients experienced considerable
      psychological dysfunction compared with controls. All aspects of psychosexual
      dysfunction were affected. CONCLUSIONS: When managing patients, psychosexual and
      psychological issues must be considered in addition to other conventional types
      of therapy. Vulvar vestibulitis may be a risk factor for developing psychosexual
      complications including vaginismus, low libido, and orgasmic dysfunction.
      Consideration of these factors must be an integral part of the management of
      patients with all chronic vulval conditions.

PMID- 9582479
TI  - Vulvodynia and HIV: causal or casual association?
AB  - BACKGROUND: No study exists on HIV and vulvodynia. OBJECTIVE: To evaluate
      vulvodynia in HIV infected women and its possible association with HIV. DESIGN:
      Cross sectional study. SETTING: Department of Medical and Surgical Sciences,
      Section of Infectious Diseases, University of Turin. METHODS: 235 HIV positive
      and 272 HIV negative women were studied for vulvar pain between June 1995 and
      January 1997. Diagnosis of vulvodynia was based on clinical history,
      dermatological and vulvovaginal examination, and bacteriology. Colposcopy and
      vulvar biopsy were performed and psychometric examination was done. RESULTS:
      Vulvodynia was diagnosed in five women with HIV and in one uninfected woman (odds
      ratio = 2.5; 95% confidence interval: 0.1-62.6). High neuroticism scores were
      observed in women with history of vulvar pain, the highest in HIV infected
      vulvodynia patients (p = 0.000). CONCLUSIONS: Confirming the association of
      gynaecological pain with neurotic personality, our study suggests causal link
      between HIV and vulvodynia.

PMID- 9582480
TI  - Necropsies in HIV medicines.
AB  - OBJECTIVE: The objective of this study was to determine the availability of
      necropsy services to departments dealing with HIV positive patients, and to
      assess their satisfaction with, and utilisation of, these services. METHOD:
      Confidential questionnaires were sent to 187 consultants in genitourinary
      medicine and infectious diseases departments within the United Kingdom and
      Ireland. One hundred and forty four (77%) replies were suitable for analysis.
      RESULTS: Seventy five (52.1%) centres had a routine necropsy service, compared
      with 59 (41.0%) which did not, including 15 (10.4%) with no service provision.
      Sixty one (42.4%) centres were satisfied with their current service; however, 31
      (21.5%) clinics were not satisfied. The majority of service users considered
      necropsies to be beneficial in the subsequent management of HIV positive
      patients. CONCLUSION: The provision of services for HIV necropsies varies
      considerably. We advocate that they should be uniformly available, and that the
      dissatisfaction with current services should be addressed.

PMID- 9582481
TI  - Knowledge of HIV infected individuals about prevention of cryptosporidiosis.

PMID- 9582482
TI  - Sexual risk behaviour among subgroups of heterosexual HIV infected patients in an
      urban setting.
AB  - OBJECTIVE: To determine the frequency of characteristics associated with
      unprotected heterosexual intercourse in HIV infected adults in an urban area.
      DESIGN: Retrospective comparison of sexual risk transmission behaviour between
      HIV infected men and women from a drug treatment site and between women from the
      drug site and HIV infected women from an urban medical centre. METHODS: HIV
      infected women and men were asked questions on sexual behaviour for a 1 year
      period before enrollment. The outcome variable was heterosexual risk behaviour
      (HRB) defined as having vaginal sex at least once in the previous year and not
      always using condoms. RESULTS: 73% of the drug clinic females, 72% of the drug
      clinic males, and 42% of the medical centre female engaged in HRB. Using logistic
      regression analysis, women and men in drug treatment engaged in similar rates of
      HRB; however, women in drug treatment were four times (95% CI = 2.0-8.3) more
      likely to engage in HRB risk behaviour than women from the medical centre.
      CONCLUSION: The data suggest that a surprisingly large portion of HIV infected
      patients under treatment engaged in HRB, especially former drug users. Without
      specifically targeted interventions, the heterosexual spread of HIV in urban
      areas will continue to be a serious problem.

PMID- 9582483
TI  - Sexually transmitted disease among married Zambian women: the role of male and
      female sexual behaviour in prevention and management.
AB  - OBJECTIVES: Few studies have evaluated the relation between male and female
      sexual behaviour and STD among married African women. The objectives of this
      study were to identify male and female sexual behaviour associated with female
      STD, and to explore whether incorporating male and female sexual behaviour and
      male symptoms can improve algorithms for STD management in married African women.
      METHODS: 99 married couples with one symptomatic member (58 males, 41 females)
      attending an STD clinic in Lusaka, Zambia were interviewed separately about
      sexual and contraceptive behaviour, and had physical examinations. Diagnostic
      tests for Neisseria gonorrhoeae (GC), Trichomonas vaginalis (TV), and HIV were
      performed. Bivariate and multivariate odds ratios for the association between
      sexual behaviour and STD were calculated. Predictive algorithms based on current
      Zambian guidelines for management of STD in women were created. RESULTS: Among
      women at baseline, 10% were positive for GC, 14% for TV, 52% for HIV. Female
      alcohol use before sex, a male's paying for sex, and a couple's having sex
      unprotected by condoms or spermicides were associated with female STD.
      Incorporation of these behaviours along with symptoms of urethral discharge and
      dysuria among husbands increased the predictive ability of algorithms for
      management of STD in women. CONCLUSIONS: The addition of male and female sexual
      behaviour and male STD symptoms to diagnostic algorithms for female STD should be
      explored in other settings. Both husbands' and wives' behaviour independently
      predict STD in these women; risk reduction programmes should target both men's
      and women's sexual behaviour.

PMID- 9582484
TI  - Family planning services in developing countries: an opportunity to treat
      asymptomatic and unrecognised genital tract infections?
AB  - OBJECTIVE: To determine the prevalence of asymptomatic and unrecognised genital
      tract infections among women attending a family planning clinic in rural South
      Africa. METHODS: 189 consecutive women had genital samples taken to diagnose
      infection with Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas
      vaginalis, Candida albicans, Treponema pallidum, and HIV, and to diagnose
      bacterial vaginosis. RESULTS: Mean age was 25 years; 155 (82%) were unmarried,
      156 (83%) were currently using contraception, and 41 (22%) reported having an STD
      treated in the preceding 12 months. Although none volunteered abnormal urogenital
      symptoms, 74 (39%) had at least one elicited by direct questioning. 119 women
      (63%) had at least one genital infection: N gonorrhoeae (eight; 4%), C
      trachomatis (14; 8%), T vaginalis (26; 14%), C albicans (56; 30%), active
      syphilis (15; 8%), HIV (44; 24%), and bacterial vaginosis (29; 15%). 49 women
      (26%) had multiple infections. Most infections (71; 60%) were asymptomatic.
      Symptomatic women failed to recognise and report their symptoms, and routine
      services failed to detect the infections. CONCLUSION: Prevalence of genital tract
      infection is high among these women, most infections are asymptomatic, and
      symptomatic infections are frequently not recognised. Women attending family
      planning clinics in such settings should be screened for syphilis and offered
      testing for HIV infection. Strategies to detect and treat other genital
      infections need to be developed.

PMID- 9582485
TI  - Genotyping of Portuguese Chlamydia trachomatis urogenital isolates.
AB  - OBJECTIVE: To determine the prevalence of the different Chlamydia trachomatis
      genotypes in Portuguese patients. METHODS: Urogenital isolates (n = 240) derived
      from attenders of various clinics in the Lisbon area were differentiated into
      genovars by genotyping with restriction fragment length polymorphism (RFLP)
      analysis of the PCR amplified omp1 gene. RESULTS: Genotype E was the most common
      for both men (47.9%) and women (43.8%). Genotypes D and F were the second most
      prevalent for men (11.3%) and genotype H was the second most prevalent for women
      (19.5%). Genotypes F, G, D, in women and H, G, I, in men, were found in a lower
      percentage of cases. Genotypes B, Ba, J, K, L1 and L2 were very rarely detected.
      CONCLUSIONS: With one exception, the overall distribution of Chlamydia
      trachomatis genotypes in our study is similar to what has been observed in other
      western countries. The only exception is the unusual prevalence of genotype H
      among women. The clinical manifestations associated with this and other genotypes
      were similar.

PMID- 9582486
TI  - Gonorrhoea: auxotypes, serovars, and clinical manifestations among female sex
      workers from Kinshasa, Zaire.
AB  - The main question in this paper was to look at the distribution of auxotypes and
      serovars of Neisseria gonorrhoeae and check whether they correlate with clinical
      symptoms/signs among female sex workers (FSW) from Kinshasa, Zaire. The subject
      were 1233 FSW enrolled in a cross sectional study on STDs and HIV infection in
      1988; 771 of them were followed prospectively for a median duration of 23 months.
      At each visit, clinical symptoms and signs of cervicitis were recorded and the
      subjects were screened for gonococcal and chlamydial infection. The pre-dominant
      auxotypes were prototrophic (35.2%), proline requiring (29.6%), and proline
      requiring phenylalanine inhibition (19%). Serovars 1A-6 (42.5%) and 1B-1 (16.7%)
      were the commonest. Infection with auxotype prototrophic and phenylalanine
      inhibition (Proto/Phenali) was significantly associated with both mucopurulent
      cervicitis and pelvic inflammatory disease; (OR = 8.9; p = 0.002 and OR =19 x9; p
      = 0.002; respectively). Despite the few associations found in this study, there
      was not clear pattern linking clinical manifestations to auxotype/serovar
      profiles.

PMID- 9582487
TI  - Balanoposthitis associated with the presence of subpreputial "smegma stones".

PMID- 9582489
TI  - Kaposi's sarcoma in retrospect.

PMID- 9582488
TI  - What is the role of the HIV liaison psychiatrist?
AB  - In this article we review the field of HIV liaison psychiatry and illustrate the
      manner in which psychiatric care can contribute to the health and quality of life
      of this group of patients. To illustrate our discussion we review experience and
      findings in relation to affective illness, cognitive impairments, and personality
      disorder in HIV infection. We also highlight some of the areas where psychiatric
      care of people with HIV infection is unique from other types of psychiatric
      liaison work.

PMID- 9582490
TI  - Kaposi sarcoma presenting as severe haemoptysis.

PMID- 9582491
TI  - Foreign body granuloma of the penis caused by occupational glass fibre exposure.
AB  - We report a patient who presented with the suspected diagnosis of syphilis.
      Clinical findings included a penile ulcer, positive history of syphilis more than
      20 years ago, and positive syphilis serology (TPHA, FTA-Abs). A biopsy showed a
      plasma-cell rich inflammation with granuloma formation. Since a birefractory
      structure was observed in the biopsy possibly corresponding to a foreign body,
      the patient's occupational exposure was investigated. Working in the fiber
      reinforced plastics industry, he was heavily exposed to glass fibre that was even
      detected on the inside of his underwear. Taking the serological pattern into
      account that was not consistent with active syphilis, a penile ulcer following a
      foreign body reaction was diagnosed. This case report demonstrates the
      difficulties of differentiating foreign body granuloma of the genital region from
      venereal diseases with granuloma formation.

PMID- 9582493
TI  - Chronic balanitis: an unusual localisation of necrobiosis lipoidica.

PMID- 9582492
TI  - Microsporum canis infection of the penis.

PMID- 9582494
TI  - Acceptability of clinics for sexually transmitted diseases among users of the
      "gay scene" in the West Midlands.

PMID- 9582495
TI  - Alternative RNA processing--its role in regulating expression of
      calcitonin/calcitonin gene-related peptide.
AB  - The calcitonin/calcitonin gene-related peptide (CT/CGRP) gene is one of the
      earliest studied examples of alternative RNA processing. The regulatory
      mechanisms controlling this event are poorly understood. We have identified and
      characterized an intron element residing in intron 4 of the human CT/CGRP gene.
      This intron element functions to enhance polyadenylation of an embedded
      alternative 3'-terminal exon within the CT/CGRP gene and is potentially involved
      in tissue-specific regulation of CT/CGRP RNA processing.

PMID- 9582496
TI  - Measurement of an analog of insulin-like growth factor-I in blood plasma using a
      novel enzyme-linked immunosorbent assay.
AB  - Long-Arg3-IGF-I (LR3IGF-I) is a synthetic analog of IGF-I that has much lower
      affinity for IGF-binding proteins than do native IGFs-I and -II. Comparisons of
      the effects of LR3IGF-I with those of IGFs-I and-II in in vitro and in vivo
      studies have proved useful in defining the functions of IGF-binding proteins. We
      have developed a sensitive noncompetitive nonisotopic assay of LR3IGF-I. Mouse
      IgG 1A7-F5-E5 binds an epitope that contains the substituted arginine3 in LR3IGF
      I and was used as the solid phase antibody. The solution phase antibody was a
      rabbit immunoglobulin Nelson which binds to an epitope that is common to IGF-I
      and LR3IGF-I. The ELISA system was able to detect as little as 50 pg LR3IGF-I in
      100 microliters and the native peptides IGFs-I and -II have less than 0.01%
      activity. Blood plasma from animals treated with pharmacologically active doses
      of this growth factor analog could be diluted 33.3-fold before assay, at which
      concentrations plasma had no significant effect on the assay. The ELISA response
      to LR3IGF-I was unaffected by the presence of IGF-binding proteins. The intra
      assay and interassay coefficients of variation are 2.8 and 7.3% respectively.
      Recovery of LR3IGF-I added to blood plasma was approximately 90%. The ELISA was
      used to measure LR3IGF-I concentrations in plasma of cows treated with a
      pharmacologically active dose of this peptide and the results were compared with
      those obtained by a previously established LR3IGF-I RIA that requires size
      exclusion chromatography of plasma under acidic conditions to eliminate IGF
      binding protein artefacts from the RIA. There was a positive correlation between
      results obtained by the two assays. The LR3IGF-I ELISA permits discrimination
      between the exogenous synthetic IGF-I analog and the endogenous native IGFs-I and
      -II in animals treated with this growth factor without the need for
      radioiodination of LR3IGF-I and elimination of the requirement for extraction of
      plasma before assay.

PMID- 9582497
TI  - Localization and expression of adrenocorticotropic hormone receptor mRNA in
      normal and neoplastic human adrenal cortex.
AB  - The recent cloning of the ACTH receptor (ACTH-R) gene allows investigation of the
      tissue localization and relative abundance of ACTH-R mRNA in normal and
      neoplastic adrenal cortex. Using in situ hybridization (ISH) we studied the
      expression of ACTH-R mRNA in four adult adrenals of brain-dead patients, two
      cortisol-producing adenomas (CPA), three aldosterone-producing adenomas (APA),
      one non-functional adenoma (NFA), and three carcinomas. The results were compared
      with the mRNA expression of key steroidogenic enzymes and of the glucocorticoid
      receptor (GR) mRNA using Northern blotting. In adult adrenals, messenger RNA
      encoding ACTH-R was localized in all three zones of the adrenal cortex, in
      accordance with the stimulatory role of ACTH on mineralocorticoid, glucocorticoid
      and adrenal androgen secretion. In comparison, expression of side-chain cleavage
      enzyme (P450scc) showed a similar tissue distribution with mRNA abundance in all
      three zones, whereas 17-hydroxylase/17-20 lyase (P450c17) mRNA expression was
      only detected in the zona fasciculata and zona reticularis. All CPAs and APAs
      expressed significant levels of ACTH-R mRNA whereas an NFA showed low expression
      of ACTH-R mRNA. Two of three adrenocortical carcinomas expressed ACTH-R mRNA.
      Northern analysis using dot blot was employed to quantify ACTH-R and GR mRNA
      expression and confirmed the ISH data: ACTH-R mRNA expression was high in CPAs
      (275 and 195% vs 100 +/- 25% in adult adrenals), APAs (127, 200 and 221%) and two
      carcinomas (99 and 132%), but low in the NFA (7%) and in an androgen secreting
      carcinoma (16%). GR mRNA expression was high in the NFA (195%) and in two of
      three carcinomas (93, 188, 227%). We conclude that ACTH-R mRNA is upregulated in
      functional adenomas by yet unidentified mechanisms. The tissue distribution of
      ACTH-R and P450 enzyme mRNA expression is highly variable in neoplastic adrenals
      and does not allow a clear differentiation between benign and malignant tumors.

PMID- 9582498
TI  - Expression of the parathyroid Ca(2+)-sensing receptor in cytotrophoblasts from
      human term placenta.
AB  - Fura-2-loaded human cytotrophoblasts responded to elevated extracellular Ca2+
      concentration ([Ca2+]o) with monophasic or, in the case of large (> 20 microns)
      extravillous cells, biphasic elevations in intracellular free Ca2+ ion
      concentration ([Ca2+]i) that returned to baseline levels after restoration of
      control [Ca2+]o. Large extravillous cytotrophoblasts also responded to elevated
      [Mg2+]o with transient elevations in [Ca2+]i, consistent with the behaviour of
      the parathyroid Ca2(+)-sensing receptor. Expression of the parathyroid Ca2(+)
      sensing receptor in placental cells was confirmed using Northern blot and reverse
      transcription (RT)-PCR analysis. However, the major transcript in human placental
      cells (6.2 kb) differed from that expressed by human parathyroid cells (5.6 kb).
      RT-PCR analysis and DNA sequencing of key PCR products also revealed the presence
      of a splice variant in placental and parathyroid cells that lacks exon 3.

PMID- 9582499
TI  - Expression of nerve growth factor and its high-affinity receptor Trk-A in the rat
      pancreas during embryonic and fetal life.
AB  - The expression of functional receptors for nerve growth factor in insulin
      producing cell lines grown in vitro has recently been demonstrated. The possible
      importance of signals transduced via these receptors in the control of islet
      maturation has been proposed based on data obtained using an in vitro culture
      system. To further support this hypothesis, we have studied the expression of Trk
      A, the high-affinity receptor for NGF, in vivo during the embryonic and fetal
      development of the rat pancreas. We have also examined the expression of NGF
      during the same period. Immunohistological analysis shows that at embryonic day
      11 (E11), Trk-A is expressed by the epithelial cells of the presumptive pancreas.
      The few pancreatic endocrine cells present at that stage express Trk-A. At E12
      and E16, Trk-A expression was detected in the developing ductal network. The
      endocrine cells located in the ducts express Trk-A while those that have migrated
      into the surrounding mesenchyme now stain negative for Trk-A. By E20, Trk-A
      expression by ductal cells has considerably decreased and can be detected only in
      small ducts closely associated with islet-like structures. These islet-like
      structures stain negative for Trk-A. After birth, insulin-positive cells arranged
      into islets re-express Trk-A. During the same period, NGF mRNA is found to be
      expressed in the developing pancreas. The expression of Trk-A and its ligand NGF
      in the pancreas during embryonic and fetal life suggests that NGF and its
      receptor could play an important role in the development of the pancreas.

PMID- 9582500
TI  - Recombinant somatolactin as a stable and bioactive protein in a cell culture
      bioassay: development and validation of a sensitive and reproducible
      radioimmunoassay.
AB  - A recombinant somatolactin (SL) obtained by cloning and expression of sole SL
      cDNA was analyzed and used to develop a sensitive and specific RIA. In contrast
      to native proteins, which tend to dimerize and aggregate immediately after
      pituitary isolation, the majority of recombinant sole SL (rsSL) remained as a
      monomeric protein after long-term storage, as shown by size exclusion
      chromatography and Western blot. Using rsSL as a tracer and standard in the RIA,
      the minimum detectable dose and the midrange (ED50) of the assay were 0.15 and
      1.8-2.1 ng/ml respectively. Intra-and interassay coefficients of variation were
      4.3% and 6.5% at ED50 levels. Recombinant gilthead sea bream GH and recombinant
      trout GH did not show cross-reactivity, whereas a good parallelism between rsSL
      standard and serial dilutions of plasma and sole pituitary extracts was observed.
      In order to demonstrate some biological activity of rsSL, the ability of this
      recombinant product to prime gilthead sea bream phagocytes for in vitro
      enhancement of mitochondrial activity was examined by a chromogenic assay. A bell
      shape dose-response curve was obtained with a maximum at 50 nM (1.2
      micrograms/ml), similar to that reported previously for GH. Therefore, taking
      together all these data, it appears conclusive that rsSL is a long-term stable
      protein which retains, at least in part, biological activity, providing a useful
      tool to clarify the physiological role of fish SL.

PMID- 9582501
TI  - Bovine adrenal glomerulosa cells express such a low level of functional B2
      receptors that bradykinin does not significantly increase their aldosterone
      production.
AB  - It was recently demonstrated that bradykinin (BK) stimulates aldosterone
      secretion in bovine adrenal glomerulosa (BAG) cells. The aim of the present study
      was to characterize the mechanism of action of BK on these cells. Binding
      experiments with the radioligand 125I-[Tyr8]BK revealed the presence of a
      relatively small amount (Bmax = 180 +/- 55 fmol/mg of protein) of high affinity
      (Kd = 0.65 +/- 0.17 nM) binding sites. BK induced a time- and concentration
      dependent increase of [3H]inositol trisphosphate ([3H]IP3) in myo-[3H]inositol
      labeled BAG cells. A maximal response was obtained with 10 nM BK and the EC50
      value was 1.0 +/- 0.5 nM. 125I-[Tyr8]BK binding and BK-induced IP3 production
      were inhibited by the selective B2 receptor antagonist Icatibant (1 microM) and
      unaffected by the selective B1 receptor antagonist [DesArg9, Leu8]BK (1 microM).
      In fura-2 loaded BAG cells, BK (100 nM) induced a typical biphasic Ca2+ response
      composed of a rapid and transient increase of intracellular Ca2+ concentration
      [Ca2+]i which slowly declined to a level that remained above basal level for
      about 5 min. In the presence of EGTA (2 mM), the rapid and transient calcium
      increase was unaffected whereas the plateau phase was abolished. Angiotensin II
      (Ang II, 100 nM) also elicited a typical biphasic response in BAG cells. However
      the rapid and transient elevation of [Ca2+]i was followed by a sustained plateau
      phase which remained above the basal level for more than 10 min. Although BAG
      cells express functional B2 receptors, no secretion of aldosterone was observed
      after stimulation with 100 nM BK for 120 min. Under the same conditions Ang II
      increased by about 10-fold the basal level of aldosterone. The lack of effect of
      BK is probably attributable to its very transient effect on IP3 production.
      Pretreatment of BAG cells with 100 nM BK for 20 min reduced by 70 +/- 10% their
      total binding capacity. These results suggest a rapid and very efficient
      desensitization process. We conclude that BAG cells express functional B2
      receptors. The weak production of second messengers and the rapid desensitization
      process could explain why BK fails to increase aldosterone production in these
      cells. Since functional B2 receptors are expressed in BAG cells it is likely that
      under some specific physiological or pathological conditions these receptors may
      play a significant role in aldosterone secretion. However these conditions remain
      to be determined.

PMID- 9582502
TI  - Interleukin-1 inhibits Leydig cell steroidogenesis without affecting
      steroidogenic acute regulatory protein messenger ribonucleic acid or protein
      levels.
AB  - The rate-limiting step of steroidogenesis is the transport of the substrate
      cholesterol from the outer to the inner mitochondrial membrane which involves a
      cycloheximide-sensitive newly synthesized protein. A protein believed to carry
      out this function was recently cloned from MA-10 mouse Leydig tumor cells and
      named the steroidogenic acute regulatory protein (StAR). In the present study, we
      evaluated the expression and regulation of StAR in primary cultures of rat Leydig
      cells. StAR mRNA was expressed in Leydig cells as two major transcripts of 3.8
      and 1.7 kb and one minor transcript of 1.2 kb. Induction of StAR mRNA transcripts
      could be detected as early as 30 min after the addition of human
      choriogonadotropin (hCG) with peak levels attained between 2 and 4 h. hCG in
      concentrations of 0.1-10 ng/ml caused a dose-dependent increase in StAR mRNA
      expression. hCG administered at a dose of 10 ng/ml increased the 3.8 kb StAR mRNA
      level about 14-fold and the 1.7 kb StAR mRNA level about 13.6-fold. hCG
      stimulated StAR mRNA was associated with increased StAR protein levels as
      determined by immunoblot analysis (a 4.5-fold increase). Murine interleukin-1
      alpha (mIL-1 alpha) at a concentration of 100 ng/ml inhibited hCG-induced
      cytochrome P450 side-chain cleavage (P450 scc) mRNA expression and testosterone
      formation almost completely. Interestingly, mIL-1 alpha had no effect on hCG
      induced StAR mRNA or protein levels. Furthermore, mIL-1 alpha (10 ng/ml)
      decreased conversion of (22R)-hydroxycholesterol to testosterone while the
      conversion of pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone and
      androstenedione to testosterone were not affected. These results indicate that
      the major inhibitory effect of IL-1 on Leydig cell function occurs at the level
      of P450 scc.

PMID- 9582503
TI  - Culture of human insulinoma cells: development of a neuroendocrine tumor cell-
      and human pancreatic islet cell-specific monoclonal antibody.
AB  - We report on the culture of human insulinoma cells derived from a 32-year-old
      male patient with hyperinsulinism due to an insulinoma of the pancreas. A single
      cell suspension was made by passing insulinoma fragments through a fine-gauge
      stainless-steel mesh. Cluster-forming insulinoma cells resembling pancreatic
      islets grew in the presence of fibroblasts. The insulinoma cell clusters could be
      differentiated from fibroblasts by using in situ pan optic staining and specific
      immunocytochemical staining (anti-human insulin and anti-human insulinoma
      monoclonal antibody (mAb) D24). mAb D24 was generated using insulinoma cells as
      antigen for immunization of a Balb/C mouse and cell fusion by the hybridoma cell
      technique. The anti-insulinoma cell mAb recognized a 32 kDa protein on immunoblot
      analysis of neuroendocrine tumor cells. D24 mAb also reacted
      immunohistochemically with normal pancreatic beta-cells and tumors such as
      vipoma, gastrinoma and carcinoid. Insulinoma cell clusters separated from
      fibroblasts by micromanipulation and plated into multiwell culture dishes
      exhibited an insulin-secretion rate of approximately 30 U/100 cells per 24 h with
      no insulin-secretory response to elevated glucose concentration. Purified
      insulinoma cells incubated with 1 ng/ml human nerve growth factor expressed
      neurofilament and neurite extension. These findings together with earlier
      observations in animal models suggest that human pancreatic beta-cells share some
      properties with neurons and are related to other neuroendocrine cells in the
      gastrointestinal tract.

PMID- 9582504
TI  - Local production and action of adrenomedullin in the rat adrenal zona
      glomerulosa.
AB  - This study was designed to investigate the synthesis and action of adrenomedullin
      in the rat adrenal gland. The results obtained from in situ hybridization and
      immunocytochemical studies suggest that adrenomedullin is synthesized not only in
      the medulla, but also within the zona glomerulosa of the rat adrenal cortex.
      Findings from in situ hybridization and binding studies also suggested that
      specific adrenomedullin receptors are expressed in the zona glomerulosa, and that
      low levels are present in the inner zones of the cortex. The Kd of the zona
      glomerulosa adrenomedullin receptor (5.5 nmol/l) suggests that it may respond to
      locally produced adrenomedullin rather than circulating concentrations of the
      peptide, which are in a lower range. It was found that adrenomedullin acted on
      zona glomerulosa cells in vitro to stimulate aldosterone release and cAMP
      formation, but in this tissue did not stimulate inositol phosphate turnover. The
      effect of adrenomedullin on aldosterone secretion was significantly attenuated by
      a protein kinase A inhibitor, suggesting that cAMP mediates the effects of
      adrenomedullin on aldosterone secretion. Adrenomedullin did not significantly
      affect the response of zona glomerulosa cells to stimulation by either ACTH or
      angiotensin II. Adrenomedullin did not affect the release of catecholamines,
      either adrenaline or noradrenaline, by intact adrenal capsular tissue. These data
      suggest that both adrenomedullin and its specific receptor are expressed in the
      rat adrenal zona glomerulosa, leading to the hypothesis that adrenomedullin may
      have an autocrine/paracrine role in the regulation of the rat adrenal zona
      glomerulosa.

PMID- 9582505
TI  - Human placenta and fetal membranes contain peptide YY1-36 and peptide YY3-36.
AB  - Extracts of human term amniotic, placental, and chorion/decidua tissue contained,
      respectively, 4.36 +/- 2.79 (pmol/g wet wt; mean +/- S.E.M.: n = 5). 2.78 +/- 0.5
      (n = 5) and 0.68 +/- 0.68 (n = 5) peptide YY (PYY)-like immunoreactivity. Using a
      specific PYY antiserum, gel filtration chromatography and reverse-phase high
      performance liquid chromatography (HLPC), amniotic, placental and fetal
      intestinal tissue extracts were demonstrated to contain PYY-like immunoreactivity
      consisting of equal amounts of PYY1-36 and PYY3-36. The presence of pancreatic
      polypeptide was not detected in any of the extracts. Positive immunohistochemical
      staining for PYY was seen in extravillous trophoblasts in the decidual septa and
      fetal membranes, the syncytiotrophoblast and cytotrophoblasts, amniotic
      epithelial cells and in maternal decidual stromal cells. Positive staining for
      PYY was found at the earliest date examined (9.5 weeks) and remained present
      throughout pregnancy to term. PYY1-36 and PYY3-36 may play important roles in
      human pregnancy, acting via endocrine or paracrine mechanisms.

PMID- 9582506
TI  - Sexual maturation in male rhesus monkeys: importance of neonatal testosterone
      exposure and social rank.
AB  - In a 5-year longitudinal study, we examined the effect of disrupting the neonatal
      activity of the pituitary-testicular axis on the sexual development of male
      rhesus monkeys. Animals in a social group under natural lighting conditions were
      treated with a GnRH antagonist (antide), antide and androgen, or both vehicles,
      from birth until 4 months of age. In antide-treated neonates, serum LH and
      testosterone were near or below the limits of detection throughout the neonatal
      period. Antide + androgen-treated neonates had subnormal serum LH, but above
      normal testosterone concentrations during the treatment period. From 6 to 36
      months of age, serum LH and testosterone were near or below the limits of
      detection. Ten of 12 control animals reached puberty during the breeding season
      of their 4th year, compared with five of 10 antide- and three of eight antide +
      androgen-treated animals. Although matriline rank was balanced across treatment
      groups at birth, a disruption within the social group during year 2 resulted in a
      marginally lower social ranking of the two treated groups compared with the
      controls. More high (78%) than low (22%) ranking animals reached puberty during
      year 4. During the breeding season of that year, serum LH, testosterone and
      testicular volume were positively correlated with social rank. Thus the lower
      social rank of treated animals may have contributed to the subnormal numbers of
      these animals reaching puberty during year 4. However, of those animals achieving
      puberty during year 4, the pattern of peripubertal changes in serum testosterone
      and testicular volume differed between control and antide-treated animals. The
      results appear to suggest that the disruption of normal activity of the neonatal
      pituitary--testicular axis retarded sexual development, but that social rank is a
      key regulatory factor in setting the timing of sexual maturation in male rhesus
      monkeys. The effect of neonatal treatment with antide and low social rank on
      sexual development could not be reversed by neonatal exposure to greater than
      normal concentrations of androgen.

PMID- 9582507
TI  - Perturbation of sheep ovarian surface epithelial cells by ovulation: evidence for
      roles of progesterone and poly(ADP-ribose) polymerase in the restoration of DNA
      integrity.
AB  - Ovarian cells within the area of impending follicular rupture in the sheep
      exhibit evidence of DNA fragmentation. Most cells undergo a degenerative process
      indicative of apoptosis and are deleted before ovulation. However, some ovarian
      surface epithelial cells located along the margins of ruptured follicles persist
      (with damaged DNA) into the ensuing luteal phase. It is conceivable that a
      genetically-altered progenitor cell that has survived a sub-lethal insult at
      ovulation (i.e. with unrepaired DNA but not committed to death) could give rise
      to a malignant phenotype that is propagated during the postovulatory ovarian
      surface wound-repair process. It was hypothesized that progesterone derived from
      the formative corpus luteum reestablishes genomic integrity among ovarian surface
      epithelial cells contiguous with the ovulatory site and that this response is
      mediated by the DNA repair/apoptosis-activating enzyme poly(ADP-ribose)
      polymerase (PARP). Ovarian surface epithelial cells immediately surrounding the
      ovulatory stigma of sheep follicles were recovered on luteal days 1, 2 or 4;
      control cells were obtained from an ipsilateral ovarian region removed from the
      point of ovulation. Immunofluorescent staining of end-linked digoxigenin or
      poly(ADP-ribose) was used to detect fragmented DNA or PARP-modified proteins
      within individual cells. Approximately 25% of surface epithelial cells that
      bordered the ovarian rupture site contained damaged DNA on days 1 and 2; there
      was a dramatic decrease by day 4 (< 5%). The decline in DNA-compromised cells was
      negated by in vivo inhibition of lutein progesterone production invoked by
      ovarian perivascular injection (day 1) of the 3 beta-hydroxysteroid dehydrogenase
      inhibitor isoxazol; this effect was reversed by exogenous progesterone. There was
      a positive relationship on day 2 between the level of ovarian progesterone and
      immunostaining of ADP-ribose polymers in surface epithelial cells associated with
      the ovulatory site. Evidence of DNA fragmentation or PARP activity in control
      cells was low and not affected by time of sample collection or treatments. The
      progesterone receptor antagonist RU486 and the transcriptional inhibitor
      actinomycin D blocked increases in PARP in ovarian surface epithelial cells
      incubated with progesterone. It is suggested that DNA damage to ovarian surface
      epithelium that is inflicted at ovulation is (normally) reconciled on a localized
      basis by progesterone/PARP-mediated repair or dedicated apoptotic cell death
      thereby conferring protection against clonal transformation.

PMID- 9582508
TI  - The localisation and expression of 5 alpha-reductase types I and II mRNAs in
      human hyperplastic prostate and in prostate primary cultures.
AB  - The expression and localisation of mRNAs for 5 alpha reductase Type I (5 alpha R
      I) and Type II (5 alpha R-II) isoenzymes in human benign prostatic hyperplasia
      (BPH) were investigated by RT-PCR and by in mini hybridisation (ISH) using
      digoxigenin labelled riboprobes. In addition, we also examined the isoenzymes
      mRNA expression in primary BPH cultures of separated stroma/fibroblast and
      epithelial cells to determine whether primary cultures are appropriate models in
      which to investigate 5 alpha R activity and regulation. The results demonstrated
      conclusively the presence of mRNA encoding both isoenzymes in all specimens so
      far examined. Additionally, the presence of a functional 5 alpha R-I and -II
      activity in BPH was confirmed by enzyme assays. ISH studies localised the mRNA
      expression to both the fibroblast/stromal component as well as the epithelial
      cells of the hyperplastic tissue. In the glandular regions the expression for
      both isoenzymes was particularly strong in the basal layers of the epithelium
      whereas mRNA expression in the secretory cells was less pronounced. Expression of
      5 alpha R-I and -II mRNAs in fibroblast was on the other hand variable with high
      expression in some areas and little in others. These findings were supported by
      our primary culture experiments which demonstrated that both the fibroblast and
      epithelial cells maintain a capacity to express both isoenzymes in vitro. In the
      case of the fibroblast, the capacity to express the isoenzymes was maintained
      following the sequential passaging of the cells up to passage 6, after which the
      cells no longer expressed either isoenzyme.

PMID- 9582509
TI  - Glutamate concentration in plasma, erythrocyte and muscle in relation to plasma
      levels of insulin-like growth factor (IGF)-I, IGF binding protein-1 and insulin
      in patients on haemodialysis.
AB  - Elevated insulin-like growth factor binding protein (IGFBP) levels, including
      IGFBP-1, occur in renal failure, and may contribute towards reduced IGF
      bioactivity in uraemia. The reduced IGF bioactivity may, in turn, contribute
      towards the disturbances in protein metabolism present in renal failure. In this
      study, the relationships between intra- and extracellular amino acid (AA) levels
      and IGF-I and/or IGFBP-1 levels were studied in 30 adult patients (aged 24-70
      years) on haemodialysis who had no clinical signs of malnutrition. Blood samples
      (n = 30) and muscle biopsies (n = 13) were collected for determination of free AA
      in erythrocytes (RBC), plasma and muscle by reverse-phase HPLC while IGFBP-1, IGF
      I and insulin plasma levels were determined by radioimmunoassay The patients on
      haemodialysis had elevated glutamate concentrations in RBC and plasma compared
      with healthy controls (524 +/- 26 vs 448 +/- 17 mumol/l, P < 0.05 and 45 +/- 4 vs
      32 +/- 4 mumol/l, P < 0.01 respectively), although glutamate levels in muscle
      were within the normal range. The mean IGF-I level was slightly increased (s.d.
      score +0.74 +/- 0.30) but insulin levels were within the normal range. IGFBP-1
      levels, which were inversely correlated to insulin (r = -0.40, P < 0.02), were
      elevated threefold compared with controls. No plasma AA level displayed a
      significant correlation with IGF-I, IGFBP-1 or insulin levels. However, glutamate
      concentrations in RBC were positively correlated to IGFBP-1 (r = 0.51, P < 0.01)
      and inversely correlated to IGF-I (r = -0.46. P < 0.01), although unrelated to
      insulin. Muscle glutamate, which was inversely related to RBC glutamate,
      displayed an opposite pattern with an inverse relation to IGFBP-1 levels (r = -
      0.73, P < 0.01) and a positive correlation to IGF-I levels (r = 0.64, P < 0.02).
      Glutamate was the only AA to display an inverse correlation between RBC and
      muscle (r = -0.65, P < 0.02, n = 12). These findings lead us to propose that, in
      uraemia, the elevated IGFBP-I levels, which reduce the bioavailability of IGFs,
      are linked to glutamate uptake in muscle, resulting in accumulation of RBC
      glutamate. Whether there is a causal relationship or the correlation is due to
      some common regulator is not clarified in the present study.

PMID- 9582510
TI  - A comprehensive evolutionary analysis based on nucleotide and amino acid
      sequences of the alpha- and beta-subunits of glycoprotein hormone gene family.
AB  - On the basis of nucleotide sequences of the coding region and their predicted
      amino acid sequences, 58 glycoprotein hormone subunit genes were compared,
      aligned and used to construct phylogenetic trees for this family. The analysis
      included 17 alpha-subunits, eight TSH beta-, six FSH beta-, 17 LH beta/CG beta-,
      four fish gonadotropin (GTH)-I beta-, five fish GTH-II beta- and one additional
      fish GTH beta-subunit. The reliability of the phylogenetic trees was probed with
      the bootstrapping test. Our results indicated that: both the alpha- and beta
      subunits of the family diverged from a common ancestral gene about 927 million
      years ago, the initial precursor of the beta-subunit duplicated to give rise to
      the LH beta and a second hormone, the latter then duplicating to FSH beta and TSH
      beta, so that FSH beta is related more to TSH beta than to LH beta; and bony fish
      GTH-I beta is highly related to mammalian FSH beta, whereas the bony fish GTH-II
      beta is more related to mammalian LH beta. For scientific consistency and
      convenience, we propose that the following nomenclature be adopted, all fish
      gonadotropins of type I be classified as FSH and all type II be classified as LH
      hormones. In addition, on the basis of results from this and other studies, we
      propose an evolutionary history for this glycoprotein hormone family.
      Reconstruction of the evolutionary history of this family would not only provide
      clues to understanding thyrotropin and gonadotropin functions, but would also
      allow further revision of the present nomenclature of the gonadotropins in fish.

PMID- 9582512
TI  - Antigoitrogenic effect of combined supplementation with dl-alpha-tocopherol,
      ascorbic acid and beta-carotene and of dl-alpha-tocopherol alone in the rat.
AB  - The effects of the vitamins dl-alpha-tocopherol, ascorbic acid and beta-carotene,
      free radical scavengers and lipid peroxidation inhibitors, were analyzed in male
      Wistar rats made goitrous by feeding a low iodine diet (< 20 micrograms
      iodine/kg) and perchlorate (1% in drinking water) for 4, 8, 16, and 32 days.
      Groups of control or goitrous rats received for at least 16 days before killing a
      diet containing 0.6% vitamin E (as dl-alpha-tocopherol acetate), 1.2% vitamin C
      (ascorbic acid) and 0.48% beta-carotene, either simultaneously (vitamin cocktail)
      or separately. This treatment led to a 5-fold increase of vitamin E in the
      thyroid gland, a 24-fold increase in the liver and a 3-fold increase in the
      plasma. In control rats, vitamin cocktail administration increased slightly the
      thyroid weight with little changes in thyroid function parameters. During iodine
      deficiency, administration of the vitamin cocktail or vitamin E alone reduced
      significantly the rate of increase in thyroid weight, and DNA and protein
      contents, as well as the proportion of [3H]thymidine labeled thyroid follicular
      cells, but not that of labeled endothelial cells. Plasma tri-iodothyronine,
      thyroxine, TSH levels, thyroid iodine content and concentration as well as
      relative volumes of glandular compartments were not modified. The proportion of
      necrotic cells rose from 0.5% in normal animals to about 2% after 16 days of
      goiter development. No significant protective effect of the vitamins was
      observed. These results suggest that these vitamins, particularly vitamin E,
      modulate one of the regulatory cascades involved in the control of thyroid
      follicular cell growth, without interfering with the proliferation of endothelial
      cells.

PMID- 9582511
TI  - Deceleration by angiotensin II of the differentiation and bone formation of rat
      calvarial osteoblastic cells.
AB  - We examined the effects of angiotensin II (Ang II) on the differentiation of rat
      calvarial osteoblastic cells and on the formation of bone by these cells.
      Northern blotting analysis revealed that Ang II inhibited the expression of mRNA
      for osteocalcin, which is a protein that is specifically expressed during
      maturation of osteoblastic cells. Ang II decreased the activity of alkaline
      phosphatase, a marker of osteoblastic differentiation, in the cells, acting via
      the type 1 (AT1) receptor. We used von Kossa staining to examine the formation of
      mineralized nodules by osteoblastic cells. Both the number and the total area of
      mineralized nodules were quantified and shown to be decreased by 10(-7) M Ang II.
      The accumulation of calcium in cells and the matrix layer was also decreased by
      Ang II. Binding analysis with subtype-specific antagonists revealed the presence
      of AT1 receptors for Ang II in this culture system. Ang II caused a marked
      increase in the rate of production of intracellular cAMP in this system. Our data
      suggest that Ang II might be intimately involved in osteoblastic metabolism
      through its interaction with the AT1 receptor.

PMID- 9582513
TI  - Follicular waves and concentrations of steroids and inhibin A in ovarian venous
      blood during the luteal phase of the oestrous cycle in ewes with an ovarian
      autotransplant.
AB  - The dynamics of ovarian follicular development and the pattern of pituitary and
      ovarian hormone concentration were investigated during the luteal phase in ewes
      with autotransplanted ovaries. The follicles were measured by ultrasound and
      samples of ovarian and jugular venous blood were collected at intervals of 12 h.
      Blood samples were collected before and after a GnRH challenge (250 ng GnRH,
      i.v.) to allow the determination of basal and LH-stimulated concentration of
      ovarian steroids. Throughout the luteal phase, large antral follicles developed
      in three waves, each of which was preceded by a rise in the concentration of FSH
      (P < 0.05). The concentrations of oestradiol and androstenedione in the
      unstimulated and LH-stimulated samples were similar (P > 0.05) during the first 3
      days of the luteal phase but differed thereafter, with the LH-stimulated being
      significantly higher than the basal concentrations (P < 0.05). In the first wave
      of follicular development the changes in follicular size were accompanied by an
      increase in the concentration of ovarian steroids and inhibin A. During the
      second follicular wave, although changes in follicle diameter were similar to the
      first wave (P > 0.05), the basal concentration of ovarian steroids and inhibin A
      remained unchanged throughout the period of emergence and demise of the large
      follicles. These results confirm that the development of large antral follicles
      during the luteal phase of the sheep occurs in successive waves that are
      associated with fluctuations in FSH secretion. However while the results strongly
      suggest that fluctuations in both inhibin A and oestradiol secretion control FSH
      during the first follicular wave, the cause of the FSH fluctuations associated
      with waves two and three is unclear. Final resolution of this issue may need to
      await the development of a specific assay for dimeric inhibin B.

PMID- 9582514
TI  - Insulin-like growth factor-I-induced DNA synthesis in insulin-secreting cell line
      RINm5F is associated with phosphorylation of the insulin-like growth factor-I
      receptor and the insulin receptor substrate-2.
AB  - A proliferative effect of insulin-like growth factor-I (IGF-I) was previously
      shown in pancreatic islets. However, the mechanism under which IGF-I actions are
      exerted in insulin-secreting cells is not clear. The rat insulinoma cell line,
      RINm5F, was shown to have both IGF-I receptors and IGF-Il/mannose-6-phosphate
      receptors. IGF-I binding to cell surface receptors stimulated phosphorylation of
      97 kDa and 93 kDa subunits of the IGF-I receptor and incorporation of
      [3H]thymidine into RINm5F cells. Both the IGF-I-induced protein phosphorylation
      and [3H]thymidine incorporation were abolished in the presence of the tyrosine
      kinase inhibitor, genistein. Under basal conditions, IGF-I did not induce insulin
      release or changes in cytosolic free Ca2+ concentration. Immunoprecipitation of
      proteins from RINm5F cells, using phosphotyrosine antibodies, followed by western
      blotting using antibody against IRS-1 revealed no distinct band of phosphorylated
      insulin receptor substrate (IRS)-1. Instead, tyrosine-phosphorylated IRS-2 was
      detected and stimulated by IGF-I when western blotting was performed using
      antibody against IRS-2. These results indicate that IRS-1 is not likely to be
      involved in IGF-I signalling in RINm5F cells. Hence, IGF-I stimulated DNA
      synthesis in RINm5F cells was associated with phosphorylation of IGF-I receptors
      and IRS-2.

PMID- 9582515
TI  - Effect of forty-eight-hour glucose infusion into rats on islet ion fluxes,
      ATP/ADP ratio and redox ratios of pyridine nucleotides.
AB  - Glucose infusion into rats has been shown to sensitize/desensitize insulin
      secretion in response to glucose. In pancreatic islets from glucose-infused rats
      (GIR) (48 h, 50%, 2 ml/h) basal insulin release (2.8 mmol/l glucose) was more
      than fourfold compared with islets from saline-infused controls and the
      concentration-response curve for glucose was shifted to the left with a maximum
      at 11.1 mmol/l. The concentration-response curve for 45Ca2+ uptake was also
      shifted to the left in islets from GIR with a maximum at 11.1 mmol/l glucose.
      Starting from a high basal level at 2.8 mmol/l glucose KCl produced no insulin
      release or 45Ca2+ uptake in islets from GIR. Islets from GIR exhibited a higher
      ATP/ADP ratio in the presence of 2.8 mmol/l glucose and marked inhibition of
      86Rb+ efflux occurred even at 3 mmol/l glucose. Moreover, in islets from GIR the
      redox ratios of pyridine nucleotides were increased. On the other hand insulin
      content was reduced to about 20%. The data suggest that a 48-h glucose infusion
      sensitizes glucose-induced insulin release in vitro in concentrations below 11.1
      mmol/l. This may, at least in part, be due to enhanced glucose metabolism
      providing increased availability of critical metabolic factors including ATP
      which, in turn, decrease the threshold for depolarization and therefore calcium
      uptake. Calcium uptake may then be further augmented by elevation of the redox
      state of pyridine nucleotides.

PMID- 9582516
TI  - Contrasting internalization kinetics of human and chicken gonadotropin-releasing
      hormone receptors mediated by C-terminal tail.
AB  - The chicken gonadotropin-releasing hormone receptor (GnRH-R) is notable for
      having a cytoplasmic C-terminal tail, which is not present in the mammalian GnRH
      Rs. We report here that the cytoplasmic tail mediates rapid agonist-promoted
      receptor internalization. The chicken GnRH-R mediated internalization of
      gonadotropin-releasing hormone (GnRH) agonist (125I[His5-D-Tyr6]GnRH) at a rate
      of 11.3%.min-1, compared with only 0.71 %.min-1 for the human GnRH-R. To
      determine whether the presence of the cytoplasmic tail was responsible for the
      more rapid internalization kinetics of the chicken GnRH-R we truncated the tail
      after the Ile336 residue (S337stop). Receptor-mediated internalization of GnRH
      agonist by the S337stop-chicken GnRH-R was much slower than in the wild-type
      chicken receptor, and was similar to the wild-type human GnRH-R (0.55 %.min-1).
      These data indicate that rapid agonist-promoted internalization of the chicken
      GnRH-R is mediated through elements in the cytoplasmic C-terminal tail, distal to
      or including Ser337 and suggests that elimination of the C-terminal tail during
      evolution of mammalian GnRH-Rs may be related to its effects on internalization.

PMID- 9582517
TI  - Expression of oestrogen receptor beta (ER beta) occurs in multiple cell types,
      including some germ cells, in the rat testis.
AB  - The identification of a second oestrogen receptor (beta) has prompted a re
      evaluation of the potential sites of action of oestrogens. The aim of the present
      study was to characterize immunoexpression of ER beta expression in the testis to
      complement earlier data which had demonstrated that expression of ER alpha is
      confined to testicular interstitial Leydig cells. In all testes studied,
      including those from both fetal (day 20.5 p.c.) and adult rats, ER beta was found
      to be expressed in multiple cell types. Sertoli cell nuclei were immunopositive
      at all ages. In adult testes expression in Sertoli cells was not stage dependent
      and was unaffected by ablation of Leydig cells. In fetal testes ER beta was also
      expressed in peritubular cells, fetal Leydig cells and gonocytes. In the pubertal
      and adult testis ER beta was detected in the nuclei of spermatogonia and most
      pachytene spermatocytes. Weak immunopositive staining was present in the
      cytoplasm of spermatocytes undergoing the second meiotic division. In conclusion
      the widespread expression of ER beta in the testis is consistent with a role for
      oestrogens in modulating spermatogenesis, and hence fertility, in the male.

PMID- 9582518
TI  - Chromosome translocations in sarcomas and the analysis of paraffin-embedded
      material.
AB  - The identification of specific chromosome translocations in various sarcomas and
      the elucidation of their molecular consequences has raised the possibility of
      detecting their presence for diagnostic and prognostic purposes in a manner
      analogous to the haematological malignancies. However, it is important to
      correlate particular translocations, and also other genetic aberrations, with
      current histological diagnoses and the behaviour of tumours, in order to assess
      the potential benefits, if any, of identifying rearrangements. Recent
      developments which enable specific translocations to be identified in archival
      material are likely to play an increasing role in the assessment and, eventually,
      the management of patients with sarcomas.

PMID- 9582519
TI  - TGF beta--a role in systemic sclerosis?
AB  - Systemic sclerosis (SSc) is a multisystem connective tissue disorder in which
      there is progressive fibrosis. Transforming growth factor beta (TGF beta) has
      wide-ranging cellular actions. It is a potent chemoattractant for human dermal
      fibroblasts, from which it may induce synthesis of collagen, which suggests that
      it may have a central role to play in the pathogenesis of SSc. This is supported
      to some extent by in vitro studies. SSc fibroblasts produce more collagens and
      fibronectin than normal fibroblasts and elevated TIMP levels have been observed,
      all of which could be explained on the basis of TGF beta stimulation of
      fibroblasts. Some studies have suggested that fibroblasts are the source of TGF
      beta. However, the serum of patients with SSc is cytotoxic to endothelial cells,
      which could culminate in TGF beta synthesis by them, with secondary fibroblast
      stimulation. The role of TGF beta remains elusive, although it would seem an
      ideal candidate as a mediator of fibrosis in systemic sclerosis.

PMID- 9582520
TI  - Dual-colour fluorescence in situ hybridization analysis of synovial sarcoma.
AB  - Mounting cytogenetic evidence indicates that synovial sarcomas, regardless of
      histological conformation, share the specific reciprocal chromosomal
      translocation t(X;18)(p11.2;q11.2). Application of dual-colour fluorescence in
      situ hybridization (FISH) on interphase nuclei isolated from archival paraffin
      embedded material to identify the specific translocation is of diagnostic
      importance for pathological practice and retrospective study. Five cases of well
      characterized biphasic synovial sarcomas, two monophasic fibrous synovial
      sarcomas, one embryonal rhabdomyosarcoma, one fibrosarcoma, and one malignant
      peripheral nerve sheath tumour were analysed. To visualize the translocated
      chromosomal fragments and their topographic relationships with centromeres of
      chromosomes X and 18, nuclei from each case were hybridized concurrently with
      chromosome X centromeric and chromosome 18 painting probes, and chromosome 18
      centromeric and chromosome X painting probes, respectively. Six out of seven
      synovial sarcomas showed chromosomal alterations consistent with t(X;18). One
      biphasic synovial sarcoma had trisomy 18 and lacked the chromosomal translocation
      t(X;18). The other three spindle cell sarcomas and the normal control tissues
      showed the normal numerical and structural composition for chromosomes X and 18.
      It is indicated from the present study that when histological differential
      diagnosis is difficult, FISH would be a crucial aid in detecting a known specific
      chromosomal alteration and that dual-colour FISH is an efficient stable
      diagnostic tool for pathological research and daily diagnosis. The results also
      suggest that rare synovial sarcomas may lack the chromosomal translocation
      t(X;18). 1998 John Wiley & Sons, Ltd.

PMID- 9582521
TI  - No p16INK4A/CDKN2/MTS1 mutations independent of p53 status in soft tissue
      sarcomas.
AB  - The p16INK4A/CDKN2/MTS1 gene encodes a specific inhibitor of cyclin-dependent
      kinases (CDKs) 4 and 6. This study investigates p16INK4A gene status and
      expression in mesenchymal tumours, in particular soft tissue sarcomas (STSs).
      Employing non-radioactive polymerase chain reaction-single strand conformational
      polymorphism (PCR-SSCP) sequencing, no p16INK4A mutation was found in 86 samples
      taken from 74 mesodermal tumours with known p53 gene status. This suggests that
      p16INK4A gene alterations, inc contrast to p53, are not involved in the
      progression of STS. This finding is supported by the reports of a low frequency
      of deletions and intragenic mutations in STS. Furthermore, by
      immunohistochemistry (IHC), an inverse correlation was established between
      p16INK4A and RB positivity for 62 per cent of the frozen tumour samples
      investigated. However, alterations in other components of the pRh/p16INK4A/
      CDK4/cyclin D1/E2F pathway have been proven crucial for tumourigenesis in human
      sarcomas.

PMID- 9582522
TI  - Cell proliferation studies in primary synovial chondromatosis.
AB  - Primary synovial chondromatosis (PSC) is thought to be a cartilaginous
      metaplasia, but it may recur locally and malignant change has been reported.
      Histologically, the cartilage is usually cellular, with binucleate forms. These
      findings suggest that the disease is not simply a metaplasia but imply a
      proliferative component. In this study, immunohistochemical detection of Ki-67
      protein using an antigen retrieval microwave heating technique and DNA image
      cytometry (VIDAS image analysis system) has been used to assess the proliferative
      activity in 20 cases of PSC and the results have been compared with those
      obtained in other cartilage tissues: ten enchondromas, ten chondrosarcomas, and
      ten samples of normal articular cartilage. There was no detectable staining for
      Ki-67 protein in cases of PSC or in benign tissues, but there was a significant
      association between Ki-67 labelling index and grade in the chondrosarcomas (P <
      0.01). The absence of mitotic figures and the lack of Ki-67 protein in PSC are
      consistent with a metaplasia. All enchondromas gave diploid DNA histograms but
      non-diploid histograms were obtained i eight cases (40 per cent) of PSC, with
      significant populations of hyperdiploid and DNA aneuploid cells. The mean DNA
      content, the percentage of hyperdiploid cells, the percentage of DNA aneuploid
      cells, and the 2c deviation index were all significantly higher in PSC than in
      enchondromas (P < 0.01). These findings with image cytometry suggest a
      proliferative process in the development of at least some cases of PSC. In terms
      of cell proliferative activity, PSC appears to occupy a position which is
      intermediate between benign enchondromas and malignant chondrosarcomas, which may
      explain the aggressive clinical behaviour occasionally seen in this condition.

PMID- 9582523
TI  - Expression of growth factors and their receptors in adamantinoma of long bones
      and the implication for its histogenesis.
AB  - Adamantinoma of long bones is a rare bone tumour with (immuno-) histological
      features of epithelial cells, surrounded by various amounts of osteofibrous
      tissue. Recent studies have indicated that cells with an epithelial phenotype are
      most probably the malignant element. There is still debate as to whether the
      fibrous part should be designed as a benign neoplastic element of a biphasic
      tumour or as a reactive non-neoplastic tissue next to an epithelioid bone tumour.
      The expression of fibroblast growth factor type 2 (FGF-2), epidermal growth
      factor (EGF), and their respective receptors FGFR-1 and EGFR, as well as the
      proliferation marker Ki-67, was studied in both constituents of adamantinoma in
      serial sections of 25 cases by immunohistochemistry. Expression of FGF-2 and its
      receptor was present in both constituents of adamantinoma, but predominated in
      the epithelial component. Expression of EGF and its receptor was restricted to
      the epithelial component of adamantinoma. Comparing osteofibrous dysplasia (OFD)
      like adamantinoma with classic epithelial cell-rich adamantinoma, the expression
      of FGF-2, EGF, and EGFR was more intense and in a higher percentage of cells in
      classic adamantinoma. Proliferative activity was found nearly exclusively in the
      epithelial component. These data further substantiate the hypothesis that
      epithelial cells constitute the proliferating tumour cell population responsible
      for the malignant behaviour of adamantinoma. The data indicate that during
      progression, the epithelial cells acquire expression of FGF-2, EGF, and EGFR,
      accompanied by a higher proliferative activity. Within the epithelial cell
      population, there exists an autocrine pathway of growth stimulation. Furthermore,
      these data point to an interaction between the epithelial and fibrous components,
      in which the epithelial cells additionally stimulate fibrous cell growth via a
      paracrine pathway involving FGF-2.

PMID- 9582524
TI  - Human tumour-associated macrophages differentiate into osteoclastic bone
      resorbing cells.
AB  - Macrophages are commonly found within osteolytic secondary carcinomas in bone,
      but the manner in which these cells contribute to malignant bone resorption is
      uncertain. Macrophages isolated from primary breast carcinomas were co-cultured
      for up to 21 days with UMR 106 rat osteoblast-like cells on bone slices and glass
      coverslips in the presence and absence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      and human macrophage colony stimulating factor (M-CSF). Cell cultures were then
      assessed for the presence of phenotypic markers of macrophage and osteoclast
      differentiation. Isolated cells were negative for osteoclast markers including
      tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and the
      ability to carry our lacunar bone resorption, but were positive for CD11b and
      CD14, macrophage markers which are not present on osteoclasts. In 21-day co
      cultures of breast carcinoma tumour-associated macrophages (TAMs) and UMR 106
      cells, incubated in the presence of 1,25(OH)2D3 and M-CSF, numerous TRAP- and VNR
      positive multinucleated cells capable of extensive lacunar resorption were
      formed. Contact with UMR 106 cells and the presence of 1,25(OH)2D3 and M-CSF were
      absolute requirements for differentiation of human breast carcinoma TAMs into
      mature functional osteoclasts. TAM-osteoclast differentiation may represent an
      important cellular mechanism of osteolysis in metastatic skeletal carcinomas.

PMID- 9582525
TI  - Expression of gap junction proteins connexin 26 and connexin 43 in normal human
      breast and in breast tumours.
AB  - Gap junctional intercellular communication (GJIC) has been proposed as a cellular
      mechanism for tumour suppression and there is experimental evidence in support of
      this. If aberrant GJIC contributes to the formation of human breast tumours, one
      might expect that the connexins (gap junction proteins) expressed by epithelial
      cells in normal human breast would be down-regulated in tumour epithelial cells,
      or that tumour cells might show aberrant expression of other connexin family
      members. This study examines the immunocytochemical expression of connexins 26
      (Cx26) and 43 (Cx43) in normal human breast, 11 benign breast lesions, two
      special-type carcinomas, and 27 invasive carcinomas of no special histological
      type (NST). Cx26 generally was not expressed at detectable level in normal human
      breast, but punctate Cx43 immunostaining of the myoepithelial cells was found.
      Cx43 staining of the myoepithelium was also a feature of the benign lesions and
      ductal carcinoma in situ (DCIS). In general, the epithelial cells of benign
      lesions failed to stain for either connexin. Similarly, a lobular carcinoma did
      not express Cx26 or Cx43, but there was punctate Cx43 in the epithelial cells of
      a mucoid carcinoma. Cx26 was up-regulated in the carcinoma cells of 15 of the 27
      invasive NST carcinomas, although the staining was usually cytoplasmic and
      heterogeneous. Cx43 was expressed by stromal cells, possibly myofibroblasts, in
      all NST carcinomas. Furthermore, there was heterogeneous Cx43 expression in the
      carcinoma cells of 14 of the 27 NST carcinomas and the staining was often
      intercellular and punctate, characteristic of functional connexins. Up-regulated
      of Cx26 and/or Cx43 in the carcinoma cells of over two-thirds of invasive lesions
      of NST is not necessarily inconsistent with a tumour suppressor role for GJIC.
      However, the role of gap junctions in the formation and progression of solid
      human tumours is likely to be more complex than indicated from experimental
      systems.

PMID- 9582526
TI  - Expression of growth factors, growth inhibiting factors, and their receptors in
      invasive breast cancer. I: An inventory in search of autocrine and paracrine
      loops.
AB  - The aim of the present study was to investigate which growth factors, receptors,
      and growth inhibiting factors are expressed in invasive breast cancer. Five
      (angiogenic) growth factors and their receptors: platelet-derived growth factor A
      chain (PDGF-AA) and PDGF receptor alpha (PDGF alpha R), PDGF-BB and PDGF beta
      receptor, transforming growth factor alpha (TGF alpha) and its receptor epidermal
      growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) and
      its receptors vascular endothelial growth factor receptor I (Flt-1) and vascular
      endothelial growth factor receptor II (Flk-1/KDR); two growth inhibiting factors:
      transforming growth factor-beta-1 (TGF beta 1) and (TGF beta 2) and their
      receptor couple transforming growth factor beta receptor I (TGF beta R-I) and TGF
      beta R-II; and basic fibroblast growth factor (bFGF) were stained by standard
      immunohistochemistry on frozen sections in 45 cases of invasive carcinoma of the
      breast. Staining was scored as negative or positive in tumour epithelium, stroma,
      and blood vessels. TGF beta 1 and TGF beta 2 were expressed in the tumour cells
      in 67 per cent and 76 per cent of cases, respectively, whereas PDG beta R and TGF
      beta R-II were expressed in 0 per cent and 2 per cent, respectively. The other
      factors showed variable expression in tumour cells. All factors were expressed in
      the stroma in most cases, except Flt-1, Flk-1/KDR, TGF beta 2, and TGF beta R-II,
      which showed variable expression, and EGFR, which showed no expression. The
      endothelium was in most cases positive for bFGF, PDGF-AA, PDGF-BB, VEGF, PDGF
      alpha R, PDGF beta R, and TGF beta 1 but TGF beta/ was negative in most cases and
      TGF alpha, EGFR, Flt-1, Flk-1/KDR, TGF beta R-I, and TGF beta R-II were variably
      expressed. The most interesting possible auto/paracrine loops, as demonstrated on
      serial sections and by fluorescence double staining, were the TGF alpha/EGFR, TGF
      beta s/TGF beta R, VEGF/Flt-1, and the VEGF/Flk-1 combinations. In conclusion,
      growth factors, growth inhibiting factors, and their receptors are frequently
      expressed in invasive breast cancer. Indications for some possible auto- and
      paracrine loops have been found, which should encourage further study on the role
      of these factors in breast cancer proliferation and angiogenesis.

PMID- 9582527
TI  - Expression of growth factors, growth-inhibiting factors, and their receptors in
      invasive breast cancer. II: Correlations with proliferation and angiogenesis.
AB  - Growth factors may play an important role in tumour growth and angiogenesis by
      their influence on tumour cell proliferation or their effect on
      neovascularization. The aim of the present study was to determine which of the
      growth factors, growth-inhibiting factors, and their receptors investigated in a
      previous study are correlated with proliferation and angiogenesis in invasive
      breast cancer, with emphasis on the impact of possible autocrine and paracrine
      loops. Five growth factors and their receptors: platelet-derived growth factor A
      chain (PDGF-AA) and PDGF alpha receptor (PDGF alpha R), PDGF-BB and PDGF beta
      receptor (PDGF beta R), transforming growth factor alpha (TGF alpha) and its
      receptor epidermal growth factor receptor (EGFR), and vascular endothelial growth
      factor (VEGF) and its receptors (Flt-1 and Flk-1/KDR; two growth-inhibiting
      factors: transforming growth factor beta-1 (TGF beta 1) and TGF beta 2 and their
      receptor couple TGF beta R-I and TGF beta R-II; and basic fibroblast growth
      factor (bFGF) were stained in 45 cases of invasive breast cancer by standard
      immunohistochemistry on frozen sections. Staining in tumour cells, stromal cells,
      and endothelial cells was scored as negative or positive. Proliferation was
      determined by assessment of the mitotic activity index (MAI) and the degree of
      angiogenesis was measure by counting the number of microvessels (microvessel
      density: MVD) in the most vascularized area of the tumour. bFGF and EGFR showed
      positive correlations with the MAI, while TGF beta 2 showed a negative
      correlation. Expression of bFGF, TGF alpha, TGF beta 2, and EGFR correlated
      positively with the MVD. Co-expression of the TGF alpha/EGFR growth
      factor/receptor combination showed a stronger correlation with the MAI and the
      MVD than EGFR or TGF alpha alone, and the TGF beta 2/TGF beta R-I/TGE beta R-II
      combination showed a positive correlation with the MVD. In conclusion, the
      expression of several growth factors, growth factor receptors and growth
      inhibiting factors showed correlations with the rate of proliferation and the
      degree of angiogenesis in invasive breast cancer. Some growth factor/receptor
      combinations showed stronger correlations with proliferation and angiogenesis
      than the growth factor or receptor alone, pointing to the importance of possible
      auto- and paracrine loops for stimulation of proliferation and angiogenesis by
      growth factors and their receptors.

PMID- 9582528
TI  - Lack of genetic changes at specific genomic sites separates renal oncocytomas
      from renal cell carcinomas.
AB  - Morphological similarities between renal oncocytomas and 'oncocytic' renal cell
      carcinomas (RCCs) make a differential diagnosis in many cases difficult. A series
      of 41 renal oncocytomas has been analysed by microsatellite markers from
      chromosomes 1, 2, 3p, 6q, 8p, 9, 10, 13q, 14q, 17, and 21, alterations of which
      are known to be involved specifically in non-papillary and chromophobe RCCs. Only
      eight of the 41 renal oncocytomas showed loss of heterozygosity (LOH). LOH at
      chromosomes 1 and 14 occurred in four tumours each and at chromosomes 2, 8, and 9
      in one tumour each. Combined LOH at chromosomes 1, 9, and 14 and also at
      chromosomes 1 and 14 occurred in one case each. No LOH was seen at any other
      genomic sites. The lack of combination of LOH at specific chromosomal sites
      differentiates renal oncocytomas from other renal cell tumours with overlapping
      phenotypes. Applying the microsatellite assay described here, the diagnosis can
      be established within 2 days, from fresh as well as from paraffin-embedded
      material.

PMID- 9582529
TI  - Predicting the risk of metachronous colorectal cancer in patients with
      rectosigmoid adenoma using quantitative pathological features. A case-control
      study.
AB  - The prognostic value of quantitative pathological features in rectosigmoid
      adenomas was investigated, in search of more precise identifiers of adenoma
      bearing patients at high risk of metachronous colorectal cancer. In a "nested
      case-control study" design, 21 cases with metachronous colon cancer during an
      average follow-up time of 16 years (range 3-30 years) after polypectomy and 67
      controls were selected from a cohort of 1618 patients. The most advanced adenoma
      of each patient was analysed. Cases were matched with up to three controls
      simultaneously for size, grade of dysplasia, histological type, and number of
      adenomas, as well as for duration of follow-up. The patients did not undergo any
      post-polypectomy surveillance. Geometric characteristics of tumour nuclei, the
      arrangement of nuclei in the epithelium, and glandular changes were measured, and
      mitoses were counted. Several quantitative features measuring nuclear
      polymorphism and crowding showed significant prognostic value, while those
      measuring glandular changes and mitotic activity did not. A multivariate
      combination of the average distance between nuclei and the standard deviation of
      nuclear area discriminated an unfavourable group (n = 44) with 17 metachronous
      cancers from a favourable group (n = 44) with four metachronous cancers (P =
      0*001, RR = 6*3). With the optimum cut-off, 28 patients without any metachronous
      cancer were discriminated from a group of 60 patients with 21 metachronous
      cancers. In conclusion, in the present study, quantitative pathological features
      assessed in rectosigmoid adenomas showed prognostic value additional to
      traditional measures. These features may therefore be useful in guiding post
      polypectomy surveillance.

PMID- 9582531
TI  - Immunohistochemical detection of ribosomal transcription factor UBF: diagnostic
      value in malignant specimens.
AB  - The nucleolar organizer regions (NORs) of human chromosome can be identified in
      interphase and mitotic cells by localization of some intrinsic components such as
      the associated enzyme RNA polymerase I. A new sensitive staining method for NORs
      is described using a specific antibody to the ribosomal transcription factor UBF.
      By indirect immunofluorescence and enzyme-labelling methods, NORs stained in
      benign and malignant cells from a variety of tissues with monospecific anti-UBF
      serum showed significant morphological differences which correlated well with
      histopathological evaluation. The number of NORs per cell in malignant
      preparations increased significantly. Furthermore, the staining of a NOR protein
      component such as UBF appears to be as sensitive as the silver-staining technique
      (AgNOR) and might be a better alternative for detecting ribosomal activity in
      malignant tissues.

PMID- 9582530
TI  - Non-radioactive measurement of telomerase activity in human bladder cancer,
      bladder washings, and in urine.
AB  - Early diagnosis is still the most important prerequisite for successful cancer
      treatment and this holds true for bladder cancer. Urine cytology is commonly used
      as a non-invasive screening procedure for the detection of bladder carcinoma, but
      this method is labour-intensive and often generates false-negative results. The
      ribonucleoprotein telomerase appears to be promising new cancer marker, since its
      activity has been reported to correlate with indefinite growth. The aim of this
      study was to investigate whether telomerase activity can be detected in bladder
      cancer and in corresponding bladder washings. For this purpose, a sensitive non
      radioactive TRAP (telomeric repeat amplification protocol) detection system was
      developed. With this technique, telomerase activity was found in 95 per cent of
      the carcinomas (n = 20), in 70 per cent of the corresponding bladder washings,
      but in none of the urine samples obtained from patients with bladder carcinoma.
      No telomerase activity was detectable in normal urothelium or in samples from
      dysplastic urothelium. The data obtained from bladder washings show that
      superficial carcinoma cells released into the bladder still harbour telomerase
      activity. The absence of telomerase activity in voided urine is thus most likely
      due to degradation or inactivation under these conditions. The high rate of
      telomerase activity in bladder carcinoma indicates that the activation of
      telomerase in a common step in the tumourigenesis of bladder cancer.

PMID- 9582532
TI  - expression patterns of cyclins D1 and E in condyloma acuminatum in comparison
      with psoriatic proliferative lesions.
AB  - Human papillomavirus (HPV) is able to subvert the host cell replication machinery
      so as to foster viral reproduction. Specifically, HPV infection is known to
      induce expression of proliferation antigens such as Ki67 and proliferative cell
      nuclear antigen (PCNA) in differentiated keratinocytes which have ceased to
      replicate. In order to determine whether cyclin D1 or cyclin E deregulation is
      also a feature of HPV infection, an immunohistochemical investigation of cyclin
      D1, cyclin E, Ki67, and PCNA expression has been carried out in 38 cases of HPV
      6/11-related condyloma acuminatum (CA). Results were compared with those obtained
      from 15 psoriatic proliferative lesions. Whereas 35 (92.1 per cent) CA samples
      exhibited positive nuclear immunostaining for cyclin E, no cyclin D1
      immunoreaction was detected in any of the CA samples studied. All psoriatic
      lesions showed immunostaining for both cyclins. All CA cases revealed a positive
      immunoreaction for Ki67 and 33 for PCNA, both in the parabasal and in the
      differentiated upper epithelial layers. Parabasal keratinocytes of psoriatic
      lesions were always positive for both Ki67 and PCNA. These results indicate that
      in the onslaught of HPV 6/11 upon the keratinocyte replication machinery, cyclin
      E, PCNA, and Ki67 are amongst the targeted cell cycle modulators, whereas cyclin
      D1 is spared the main effects of virus-cell interplay. In contrast, both cyclins
      seem to be induced in psoriasis, a non-viral proliferative skin condition.

PMID- 9582533
TI  - The C-X-C chemokine Mig is highly expressed in the papillae of psoriatic lesions.
AB  - A prominent feature within the histopathological changes of psoriatic lesions is
      the particular spatial distribution of neutrophils, macrophages, and T-cell which
      are considered to participate in the pathogenesis of psoriasis. In this study, an
      attempt has been made to examine the microanatomical localization and magnitude
      of expression of the T-cell-attractant and -stimulating C-X-C and C-C chemokines
      Mig, interferon-inducible protein-10 (IP-10), macrophage inflammatory protein-1
      alpha and 1 beta (MIP-a alpha and 1 beta), and regulated on activation, normal T
      cell expressed and secreted (RANTES). Employing in situ hybridization, Mig
      message was strongly and selectively expressed in the upper lesional dermis with
      pronounced clustering in the tips of the papillae, whereas expression in normal
      or uninvolved skin was quiescent. In contrast, message for all the other
      chemokines investigated was much weaker or lacking. Expression of Mig transcripts
      in cell clusters of the papillae was paralleled by Mig immunoreactivity on
      endothelial and mononuclear cells. The expression profile, with high levels of
      Migs virtually limited to those lesional papillae with a pronounced infiltration
      of mononuclear leukocytes, strongly suggests that Mig is produced by a local
      population of highly activated macrophages and dermal microvascular endothelial
      cells. Considering the T-cell-attracting and -stimulating capacity of Mig and the
      importance of T-cells in the pathogenesis of psoriasis, this study indicates that
      this novel C-X-C chemokine plays an important role as a mediator of T-cell
      recruitment and activation in the papillae and thus contributes significantly to
      the cytokine network of inflammation in psoriasis.

PMID- 9582534
TI  - Differentiation of BCG-induced lymphadenitis from tuberculosis in lymph node
      biopsy specimens by molecular analyses of pncA and oxyR.
AB  - Without culture, differentiation of bacille Calmette-Guerin-induced lymphadenitis
      (BCG-LA) from tuberculosis (TB) is sometimes difficult by histology, but is
      important because of different treatment schemes. The purpose of this study was
      to investigate the feasibility of differentiating BCG-LA from TB in lymph nodes
      (LNs) by molecular analyses of two recently identified genes, pncA and oxyR. In
      both genes, a single tuberculosis difference exists between Mycobacterium bovis
      and M. tuberculosis. M tuberculosis complex (MTC) DNA was first detected in nine
      of ten formalin-fixed, paraffin-embedded LNs from patients aged under 20 years
      with suspected mycobacterial infections, using polymerase chain reaction (PCR)
      for IS6110, an insertion sequence specific for MTC species. PCR, together with
      direct DNA sequencing and PCR-restriction fragment length polymorphism (RFLP)
      assay, was then performed to identify polymorphic nucleotide in pncA and oxyR,
      respectively. For comparison, 37 adult cases of tuberculous lymphadenitis were
      also analysed by PCR-single strand conformation polymorphism (SSCP) assay for
      pncA and by PCR-RFLP for oxyR. The results revealed that five of the nine IS6110
      positive child cases had a G residue at nucleotide 169 in pncA, and also had a
      three-band pattern after digesting the amplified oxyR segment with AluI,
      suggesting BCG-LA. The remaining four child cases, as well as all adult cases
      with detectable IS6110, showed no motility shift in pncA PCR-SSCP and had the
      same one-band pattern as M. tuberculosis in oxyR PCR-RFLP, suggesting TB
      lymphadenitis. The data from molecular analyses showed a good correlation with
      the vaccination history and clinicopathological findings, except for one case.
      This study indicates that molecular assay of either oxyR or pncA could be a rapid
      and useful tool to distinguish BCG-LA from TB.

PMID- 9582535
TI  - Multiple organ involvement during experimental cytomegalovirus infection is
      associated with disseminated vascular pathology.
AB  - Since much of the pathogenesis of cytomegalovirus (CMV) disease is still unknown
      and vascular involvement may be of importance a rat model was used to study the
      nature and course of CMV-induced vascular pathology. In this model, local CMV
      infection was established by subcutaneous inoculation of rat-specific CMV (RCMV)
      in the sole of the foot. Sings of endothelial activation, including leucocyte
      adhesion, preceded detectable RCMV infection of these cells. ultimately,
      vasculitis and thrombotic occlusion were accompanied by diffuse tissue
      inflammation and necrosis. Generalized RCMV infection was induced in rats by
      intraperitoneal administration of the virus, which resulted in multiple organ
      pathology, including haemorrhages, inflammation, and gastrointestinal ulceration.
      RCMV-encoded antigens were found especially in mononuclear inflammatory cells in
      the organs and peripheral blood. In addition, multiple haemorrhages and disturbed
      haematological parameters indicated diffuse intravascular coagulopathy. In
      conclusion, this study provides evidence for extensive vascular involvement and
      haematological consequences during disseminated CMV infection. The nature and
      chronology of RCM-induced pathological vascular events were demonstrated,
      indicating the importance of endothelial damage. These data and further study may
      lead to a better understanding of the pathogenesis of CMV multiple-organ disease.

PMID- 9582536
TI  - Pathology and the OSCE: insights from pilot study.
AB  - Undergraduate medical education in Manchester in undergoing wholesale revision,
      with the introduction of problem-based learning (PBL) in each successive year of
      the curriculum, as the cohort of students who joined the faculty in 1994 advances
      through the course. This cohort has now entered year 3, which primarily hospital
      based. In preparation for this, we have explored the development of an OSCE, not
      only to assess core interpersonal skills such as history taking, clinical
      examination, and the ability to explain things to patients, but also to integrate
      the examination of important skills relating to investigational sciences. These
      include the correct choice of laboratory tests, accurate interpretation of data,
      and appropriate selection of clinical responses to test results.

PMID- 9582537
TI  - Diagnostic discord with melanoma.

PMID- 9582538
TI  - Breast screening evaluation.

PMID- 9582539
TI  - Endoscopic management of Bouveret's syndrome.

PMID- 9582540
TI  - Is there any evidence that treating gastric cancer with chemotherapy or
      radiotherapy is better than surgical resection alone?

PMID- 9582541
TI  - Novel molecular mechanism for infectious diarrhea due to enteropathogenic
      Escherichia coli.

PMID- 9582542
TI  - Comparison of activity of 10 antibiotics against clinical strains of Helicobacter
      pylori by three different techniques.
AB  - The authors determined the susceptibility of 55 single clinical strains of
      Helicobacter pylori isolated in the Montreal area to 10 antibiotics by three
      different methods--an agar dilution technique considered to be the gold standard,
      a disk diffusion method and the E-test. Testing was performed on Mueller-Hinton
      agar supplemented with 10% sheep blood; plates were incubated at 37 degrees C for
      72 h in a microaerophilic atmosphere. The metronidazole resistance rate is about
      11% in the Montreal area. Macrolides are very active against H pylori isolates,
      with few variations in activity between older and newer molecules. Correlation
      among different methods was not as good as reported in the literature for
      metronidazole.

PMID- 9582543
TI  - The evolving role of endoscopic retrograde cholangiography before and after
      cholecystectomy.
AB  - Laparoscopy is the preferred approach for cholecystectomy; however the
      indications for pre- versus postoperative endoscopic retrograde cholangiography
      (ERC) are still evolving. The records of patients who had ERC performed one month
      before (n = 119) or after (n = 35) laparoscopic or open cholecystectomy from
      January 1990 to August 1992 (period 1), and 66 patients who had preoperative ERC
      from November 1995 to October 1996 (period 2) are reviewed, ERC indications,
      findings and outcomes were reviewed, and trends in the use of preoperative ERC
      from 1990 to 1996 were sought. Between periods 1 and 2 the yield of preoperative
      ERC increased from 36% to 58% (P < 0.01). The use of preoperative ERC for the
      indication of abnormal liver enzymes declined (P < 0.05), while the yield
      increased (25% versus 61%, P < 0.01). Both the use of ERC and the yield remained
      stable for other indications. ERC was felt to have changed the surgical approach
      in 5% of patients. Primary indications for postoperative ERC (n = 35) included
      abnormal intraoperative cholangiography (43%), liver function test abnormalities
      (23%) and recurrence of preoperative symptoms (14%); stones were found in 60%,
      50% and 20% of patients with these indications, respectively. Overall, 46% of
      postoperative studies revealed duct stones. The roles for pre- and postoperative
      ERC are changing and depend greatly on the relative laparoscopic and endoscopic
      expertise at a given institution.

PMID- 9582544
TI  - Overview of olestra: a new fat substitute.
AB  - Olestra is a mixture of hexa-, hepta- and octa-esters formed from the reaction of
      sucrase and long chain fatty acids isolated from edible oils. Olestra has
      properties similar to those of traditional triglycerides but is not hydrolyzed by
      pancreatic lipases and, therefore, serves as a noncaloric replacement for fats in
      the diet. The safety of olestra has been established in over 100 studies in seven
      different species of animals, with confirmatory safety data coming from
      approximately 75 human studies; consumption of olestra at levels typical for
      savoury snacks does not result in reports of gastrointestinal problems in humans.
      This is consistent with the results of studies of the physiological and
      morphological effects of olestra in animals and in humans. It is anticipated that
      olestra will be available in Canada in the near future. Patients will soon be
      asking their physicians about its use. This article provides an overview of
      olestra.

PMID- 9582545
TI  - Nutrition and chronic liver disease.
AB  - Malnutrition frequently occurs in patients with chronic liver disease, and may
      influence both short and long term clinical outcome in these patients. Therefore,
      nutritional intervention may play an important role in the management of chronic
      liver disease patients. Recent progress in nutritional assessment, principles of
      nutrition management and the impact of malnutrition upon the clinical outcome of
      chronic liver disease are reviewed and summarized. Recommendations on how to
      manage/prevent malnutrition in these patients will be presented.

PMID- 9582546
TI  - Selecting candidates for liver transplantation: a medical ethics perspective on
      the microallocation of a scarce and rationed resource.
AB  - Liver transplantation has evolved over the past 35 years from an experimental
      procedure with high perioperative mortality to an accepted form of treatment with
      an approximate 85% one-year and 80% three-year patient survival rate. Following
      the success and acceptance of transplantation in the treatment of end-stage liver
      disease, there has been a progressive increase in the number of patients seeking
      a limited supply of donor organs. The ethical focus, on a microallocation level,
      has therefore changed from that of the 1960s, when the question was whether the
      procedure should be offered at all, to that of the 1990s and beyond, when the
      focus is on the proper allocation of a scarce, life-saving resource. The ethical
      issues concerning fair allocation surrounding liver transplantation are explored,
      from both the referring physician's perspective and the perspective of the
      transplant physician. In particular, the contrasting viewpoints of bioethicists
      Nicholas Rescher and James Childress, with respect to nonmedical and social
      criteria in the selection of patients for scarce, life-saving therapies are
      explored. Lastly, some alternative ethical models for patients selection are
      reviewed.

PMID- 9582547
TI  - Churg-Strauss syndrome leading to small bowel infarction: an unusual case of
      abdominal pain in a young patient.
AB  - A 33-year-old man with a history of severe asthma presented to the emergency
      department with a week-long history of severe unrelenting abdominal pain, nausea
      and decreased appetite. He was admitted to hospital, and routine gastrointestinal
      investigations were performed, which did not elucidate the cause of his abdominal
      pain. Exploratory laparotomy demonstrated patchy infarction of the entire small
      bowel, characteristic of Churg-Strauss syndrome. The patient subsequently
      underwent 12 separate laparotomies to salvage surviving small bowel. The patient
      is maintained on total parenteral nutrition.

PMID- 9582548
TI  - Omeprazole for refractory gastroesophageal reflux disease during pregnancy and
      lactation.
AB  - Symptomatic gastroesophageal reflux is a common complication of pregnancy and
      lactation. However, the safety of many effective medical therapies, including
      oral proton pump inhibitors, has not been well defined. The administration of
      oral omeprazole to a 41-year-old female during the third trimester of pregnancy,
      after ranitidine and cisapride failed to control her refractory gastroesophageal
      reflux, is reported. No adverse fetal effects were apparent, and the patient
      elected to continue omeprazole therapy (20 mg/day) while breastfeeding. Peak
      omeprazole concentrations in breast milk (58 nM, 3 h after ingestion) were less
      than 7% of the peak serum concentration (950 nM at 4 h), indicating minimal
      secretion. Although omeprazole is a potentially useful therapy for refractory
      gastroesophageal reflux during pregnancy and lactation, further data are needed
      to define better its safety and efficacy.

PMID- 9582549
TI  - Alcohol abuse: potential role in electrolyte disturbances and kidney diseases.
AB  - The present review summarizes the current knowledge on the multiple effects of
      alcohol overconsumption on the kidney function as well as on water, electrolyte
      and acid-base homeostasis. In contrast to the well known transitory diuretic
      effects, the overall long-term effect of chronic alcohol overconsumption is water
      and salt retention with expansion of extracellular volume. Furthermore, depletion
      of magnesium, phosphate and calcium is also frequently found in alcohol-dependent
      patients. These electrolyte disturbances may be associated with the alcohol
      induced hypoparathyroidism and parathyroid hormone resistance of the skeletal
      muscle as well as with the decrease of serum osteocalcin. Metabolic acidosis with
      lower arterial blood pH and plasma bicarbonate concentrations was revealed in
      alcoholic patients upon admission and a significant correlation between chronic
      alcohol overconsumption and increased incidence of hyperuricemia and gout attacks
      was also reported. Alcohol seems to have dual effects on the blood pressure.
      Increased blood pressure was demonstrated in men above 80 g and in women above 40
      g ethanol consumption daily. In contrast, young adults consuming only 10 to 20 g
      per day had lower blood pressure than the abstinent group indicating a J-curve
      relationship. This is in line with the lowered risk for coronary heart disease
      associated with regular consumption of small alcohol amounts. The mechanisms
      responsible for the association between alcohol overconsumption and
      postinfectious glomerulonephritis have not been elucidated yet. Finally severe
      alcohol abuse predisposes to acute renal failure and seems to be associated with
      the general catabolic effects.

PMID- 9582550
TI  - D-amino acid oxidase activity in urine obtained from patients with renal
      disorders.
AB  - D-amino acid oxidase (DAO) is an enzyme released from the kidney, and a method
      for its enzymatic assay was developed by our group for urine specimens. A
      clinical evaluation of the test was performed for healthy individuals and
      patients with various types of nephropathy. 1) The normal reference interval was
      0-10.0 micrograms/g Cr for randomly-collected urine. The intra-assay CV was 3.5
      9.4%, and the inter-assay CV was 4.5-9.8%. 2) Urinary DAO index correlated well
      with changes in urinary microalbumin and N-acetyl-beta-glucosaminidase. 3)
      Chronic renal failure generally showed high levels of DAO, except for nephrotic
      syndrome, in which changes were minimal after the acute stage. In the nephrotic
      syndrome, urinary DAO was elevated in the acute stage with high proteinuria, but
      went down to almost normal as the proteinuria improved, although DAO changes did
      not correlate with the changes in the degree of proteinuria in lupus nephritis.
      4) DAO changes were more sensitive than those of N-acetyl-beta-glucosaminidase or
      alpha 1-microglobulin in the clinical course of renal disorders. From these
      findings, DAO was judged to be very useful for monitoring the severity of renal
      dysfunction.

PMID- 9582551
TI  - Serum cystatin C as a determinant of glomerular filtration rate in children.
AB  - The serum levels of cystatin C and creatinine were determined in a population
      comprising 69 children, 1-16 years old, and including children with both normal
      and reduced glomerular filtration rate (GFR) as determined by Cr-EDTA clearance
      measurement. The overall correlation between the reciprocal cystatin C
      concentration and GFR was significantly stronger (p < 0.05) than that between the
      reciprocal creatinine concentration and GFR and this was true also for the
      subpopulation of children with reduced GFR. Receiver-operating characteristic
      analysis also indicated superior diagnostic accuracy of serum cystatin C compared
      to that of serum creatinine for reduced GFR. The serum cystatin C reference
      values (mean +/- 1.96 SD) determined for children over one year of age was 0.63
      1.33 mg/l, which is similar to that previously determined for adults. Serum
      cystatin C appears to be an attractive alternative to creatinine for estimation
      of GFR not only in adults, but also in children.

PMID- 9582552
TI  - Absence of H(+)-ATPase in the intercalated cells of renal tissues in classic
      distal renal tubular acidosis.
AB  - Proton-secretory defect is thought to be a major pathophysiologic mechanism
      leading to classic distal renal tubular acidosis (dRTA). However, there have been
      only two case reports demonstrating the absence of proton pump in renal tissues
      of the patients with Sjogren's syndrome. This study presents two cases of classic
      dRTA in which the absence of intact H(+)-ATPase was shown in their renal biopsy
      tissues by immunohistochemistry using a rabbit polyclonal antibody against the 70
      kDa catalytic subunit of H(+)-ATPase from bovine brain clathrin-coated vesicles;
      one of the cases is diagnosed as subclinical Sjogren's syndrome and the other is
      idiopathic dRTA. A normal human kidney (NC) and the renal biopsy tissues from a
      patient with chronic tubulointerstitial nephritus whose proton secretory capacity
      was intact (DC) were compared as controls. The first patient, a 26-year-old
      woman, presented with quadriparesis. Her serologic tests revealed positive
      autoantibodies (ANA, SSA; SSB & RF), and a lower lip biopsy confirmed the
      diagnosis of Sjogren's syndrome. The second patient, a 43-year-old woman, who
      initially presented with a pathologic fracture of both femoral necks was referred
      for an evaluation for hypokalemia by the Department of Orthopedic Surgery. Her
      renal ultrasonography showed medullary calcification, and no autoantibodies were
      positive. Serum electrolytes and blood gas analyses of the two patients indicated
      severe hypokalemia and metabolic acidosis, and proton secretory defects were
      shown by a failure to lower the urine pH during marked acidemia induced by NH4Cl
      loading and an abnormally low urine-blood pCO2 difference during bicarbonate
      administration. While stainings with the anti-H(+)-ATPase antibody in NC and DC
      were strongly positive in intercalated cells in the connecting tubules and
      collecting ducts, the tissues from both patients with dRTA were devoid of any
      anti-H(+)-ATPase staining in the intercalated cells. These results support that
      the pathophysiologic basis of impaired H+ secretion in idiopathic classic dRTA as
      well as Sjogren's syndrome is the absence of intact H(+)-ATPase pumps in the
      intercalated cells.

PMID- 9582553
TI  - Hyperhomocyst(e)inemia in renal transplant recipients with and without
      cyclosporine.
AB  - Studies have demonstrated that hyperhomocyst(e)inemia is present in renal
      transplant recipients and is correlated with cardiovascular disease. It is still
      unclear whether hyperhomocyst(e)inemia observed in renal transplant recipients
      solely depends on the moderate reduction of renal function in these patients or
      if additional mechanisms are operative in this patient category. A recent study
      suggested that cyclosporine (CsA) increased plasma homocyst(e)ine concentration
      in interfering with folate-assisted remethylation of homocysteine. To confirm
      this hypothesis, we studied plasma homocyst(e)ine folic acid and cobalamin
      concentrations in 122 renal transplant recipients (104 on CsA and 18 not
      receiving CsA). After adjusting for age, gender, transplant duration and serum
      creatinine concentration, patients with and without CsA had similar plasma
      homocyst(e)ine concentrations (17.9 +/- 6.1 mumol/l in CsA(+)patients vs 17.1 +/-
      5.6 mumol/l in CsA(-)patients; p = 0.3). Moreover, we found a significant inverse
      relationship between plasma homocyst(e)ine and folic acid concentrations in both
      CsA(+) (r = 0.218; p < 0.01) and CsA(-) (r = -0.678; p < 0.05) patients. Patients
      with a past history of cardiovascular incidents had higher plasma homocyst(e)ine
      concentrations than those without cardiovascular antecedent (20.5 +/- 7.8 mumol/l
      vs. 18.01 +/- 9.9 mumol/l; p < 0.05. To conclude: 1, We did not find any
      influence of CsA on plasma homocyst(e)ine concentrations. 2. We demonstrated that
      as in other patient category, plasma folic acid and homocyst(e)ine concentrations
      are significantly correlated in CsA(+) patients. 3. Homocyst(e)ine-lowering
      therapy would be prescribed in CsA(+) patients to allow correction of
      hyperhomocyst(e)inemia.

PMID- 9582554
TI  - Incidence and long-term significance of transient ST segment deviation in
      hemodialysis patients.
AB  - Coronary artery disease is a frequent complication of end-stage renal disease
      (ESRD). ST segment depression on ambulatory electrocardiography without patient
      awareness is a marker of what has been termed "silent ischemia". It has been
      suggested that in patients with coronary artery disease these transient ST
      segment depressions are associated with increased cardiovascular mortality. Up to
      30% of patients with ESRD may display transient ST segment depression, however
      the significance of this finding in these group of patients who frequently have
      associated LV hypertrophy, and rapid electrolyte changes has not been clear. We
      therefore set out to determine the incidence of transient ST segment depression
      during ambulatory Holter monitoring in 70 consecutively studied hemodialysis
      patients. Sixty-seven patients wore the monitor for at least 12 hours and 16
      patients (23%) demonstrated at least one minute of 1 mm ST segment depression.
      The presence of clinically apparent coronary artery disease, diabetes, left
      ventricular hypertrophy, sex or race were not significantly associated with the
      probability of demonstrating transient ST segment depression. The survival of
      patients with or without transient ST segment depression was the same at 2 years
      with 70% of patients remaining free of death, nonfatal myocardial infarction, or
      coronary bypass grafting. We conclude that patients with ESRD frequently
      demonstrate transient ST segment depression, however, the presence of these
      findings on ambulatory Holter monitoring does not appear to be associated with
      increased long-term mortality.

PMID- 9582555
TI  - QT interval prolongation in the patients receiving maintenance hemodialysis.
AB  - QT prolongation is associated with a poor prognosis in patients with various
      diseases. The pathogenesis of the long QT syndrome is not well understood and
      little is known about the QT interval in the patients receiving maintenance
      hemodialysis. We evaluated changes in the QTc interval and investigated factors
      that contribute to its prolongation in 42 patients receiving maintenance
      hemodialysis. We also examined the association between the QTc interval and
      ventricular arrhythmias on 24-h ambulatory electrocardiograms. Comparison of
      standard 12-lead electrocardiograms of 42 patients and of 30 healthy controls
      matched for age and sex showed that the QTc interval in the patients was
      significantly prolonged (432.6 +/- 24.9 vs 402.0 +/- 21.0 ms, p <0.001).
      Multivariate analysis using stepwise multiple regression identified diabetes
      mellitus and the ejection fraction measured by echocardiography as independent
      risk factors for QTc prolongation. The QTc interval was significantly prolonged
      in patients with complex VPCs (couplets or salvos) (n = 13, 447.9 +/- 14.4 ms) on
      24 h ambulatory ECG compared with simple VPCs (none or occasional) (n = 29, 425.6
      +/- 25.8 ms) (p = 0.03). In conclusion, the QTc interval was prolonged in
      patients receiving maintenance hemodialysis and QTc prolongation was associated
      with complex VPCs. Decreased myocardial contractility and diabetes mellitus
      contributed to QTc prolongation.

PMID- 9582556
TI  - Calcitriol oral therapy for the prevention of secondary hyperparathyroidism in
      patients with predialytic renal failure.
AB  - Secondary hyperparathyroidism is a common feature of chronic renal failure and
      vitamin D deficiency plays an important role in the development of this
      abnormality. Several therapeutical calcitriol schedules have been used in
      treating uremic hyperparathyroidism but recently oral boluses have been proposed
      as more effective. In this study we compare the efficacy of three different oral
      calcitriol regimens in suppressing iPTH secretion in predialytic chronic renal
      failure. Sixteen (16) patients (mean age 51 +/- 16 years; creatinine clearance
      22.9 +/- 9.8 ml; range 8-32 ml/min) were treated in a cross-over randomized
      design with oral daily calcitriol 0.5 micrograms/die (Treatment A), three oral
      boluses of 2 micrograms of calcitriol a week (Treatment B) and a single oral
      bolus of 2 micrograms of calcitriol a week (Treatment C). All treatment periods
      lasted three months and were followed by a wash-out period of one month. Serum
      iPTH (Allegro Nichols), 1-25 vitamin D (IRMA-MAB), total and ionized calcium
      (Nova 8 Pabish), serum phosphate, alkaline phosphatase and creatinine clearance
      were measured every two weeks. Serum iPTH was also determined in a control group
      of fifteen (15) patients (mean age 47 +/- 12 years, creatinine clearances of 21
      +/-12 ml/min) observed for three months without calcitriol treatment. Daily oral
      intake of 0.5 micrograms of calcitriol prevents an increase of iPTH without
      causing hypercalcemia, but only oral boluses (B and C) decreased iPTH: from 270
      +/- 169 pg/ml to 135 +/- 76 pg/ml (p < 0.01; B) and to 165 +/- 121 pg/ml (p <
      0.05; C). Serum iPTH increased from 293 +/- 121 to 323 +/- 129 pg/ml (p = n.s.).
      No significant differences in renal function were observed during the different
      study periods. Our results confirm the good efficacy of multiple calcitriol oral
      boluses but also suggest for the first time a single weekly bolus as a reliable
      approach to the treatment of secondary hyperparathyroidism in pre-dialytic renal
      failure.

PMID- 9582558
TI  - Pasteurella multocida peritonitis in peritoneal dialysis.
AB  - Pasteurella multocida infection may occur in multiple sites to include rare
      involvement of the peritoneal cavity in peritoneal dialysis patients. Six cases
      of peritonitis associated with this organism have been reported in patients
      undergoing continuous peritoneal dialysis. A history of close contact with
      household cats was noted in all cases, with direct trauma to the dialysis tubing
      frequently seen. In this setting the organism appears to have a short incubation
      period with florid growth within 24 hours of known contamination. We report a
      case of Pasteurella multocida peritonitis in a patient treated with continuous
      cycling peritoneal dialysis and review the literature.

PMID- 9582557
TI  - Hernia development in CAPD patients and the effect of 2.5 l dialysate volume in
      selected patients.
AB  - The aim of this study was to estimate the prevalence of hernia formation in CAPD
      patients and to study the effect of increased dialysate volume (2.5 l) in
      selected population of patients who could tolerate it. We reviewed the charts of
      454 individuals treated with CAPD in our center during a five-year period
      (September 1991-September 1996). Out of 404 patients who used 2.0 l dialysate
      exchange volume forty-nine (11%) developed hernia (umbilical 53%, inguinal 33%,
      incisional 14%) after having been on CAPD for an average of 10 +/- 11 months,
      while only one of the 50 patients who would tolerate 2.5 l developed a hernia
      (inguinal 2%), after having been on CAPD for 12 months. All hernias were repaired
      surgically and most of the patients returned to CAPD after temporary intermittent
      peritoneal dialysis. Age, sex, nutritional status, polycystic kidneys, and
      diabetes do not seem to be predisposing factors for hernia formation, while
      previous operation for aortic abdominal aneurysm repair, or low body weight (< 60
      kg) were risk factors. The use of increased dialysate volume (2.5 l) in patients
      who could tolerate it, did not result in a higher frequency of hernia
      development. Surprisingly, patients with hernias seem to have a higher mortality
      than those without.

PMID- 9582559
TI  - Chronic bronchiectasis and anti-myeloperoxidase antibody related rapidly
      progressive necrotizing glomerulonephritis.
AB  - We reported two cases of chronic bronchiectasis and rapidly progressive
      necrotizing glomerulonephritis/severe renal failure which were also positive for
      anti-myeloperoxidase antibody, and followed their treatment and outcome.
      Immunosuppressive therapy was complicated by superimposed chest infection in both
      cases. Nonetheless, cautious use of immunosuppressive and antibiotic therapy
      reversed dialysis-dependent renal failure in one of the two cases.

PMID- 9582560
TI  - Mesalazine-associated tubulo-interstitial nephritis in inflammatory bowel
      disease.
AB  - The 5-aminosalicylic acid (5-ASA) is currently the treatment of choice for
      patients with inflammatory bowel disease. It can be administered as sulfasalazine
      (5-ASA + sulfapyridine), mesalazine (5-ASA + resins or gels) and olsalazine (two
      molecules of 5-ASA). The recent trend has been to use formulations without
      sulfapyridine since they produce less side-effects although some cases of
      nephrotoxicity have been described. We report the case of a young female with
      Crohn's disease treated with mesalazine (400 mg every 8 hours) over a period of
      12 months who developed acute interstitial nephritis. The characteristic features
      of renal function impairment were an insidious onset with non-specific laboratory
      data and progression towards a chronic state which partially improved with
      steroid treatment. In summary, it is important to bear this possibility in mind
      when confronted by any renal impairment which cannot be related to a relapse of
      inflammatory bowel disease. Renal function should be monitored routinely in
      patients receiving mesalazine at least during the first year of treatment and
      annually thereafter.

PMID- 9582561
TI  - Bilateral renal cortical necrosis associated with cefuroxime axetil.
AB  - Cefuroxime axetil has been associated with few reported adverse effects. We
      report a case of bilateral renal cortical necrosis in a female after receiving 7
      doses over 4 treatment days. The patient presented with worsening symptoms
      consisting of arthralgias, pruritus, and abdominal pain. Laboratory data obtained
      was indicative of worsening renal failure and thrombocytopenia. The patient
      required hemodialysis by the third day. Kidney biopsy revealed cortical necrosis.
      The possible pathogenesis of cefuroxime axetil causing cortical necrosis in this
      case and a review of other reported cases of chemical induced renal cortical
      necrosis is discussed.

PMID- 9582562
TI  - Clinical features of asymmetrical kidneys.

PMID- 9582563
TI  - Metastasis of unknown origin: the role of fine-needle aspiration cytology.
AB  - Metastasis of unknown origin (MUO) manifests either as a tumor deposit in an
      organ, often cervical lymphadenopathy, or as a multiorgan carcinomatosis. As a
      diagnostic and therapeutic challenge, the definition of its cell type and
      possibly its origin is imperative, although a limited diagnostic investigation is
      usually recommended. At Hines VA Hospital from 1986 to 1994, there were 116 cases
      with admitting clinical diagnosis of MUO, evaluated by fine-needle aspiration
      cytology (FNAC). The ages of patients ranged from 29 to 82 years (mean 56 years).
      All were male; Caucasians predominated. The FNAC examination with Diff-Quik and
      Papanicolaou smears were complemented with special and immunostains in 48 cases
      (41%) and electron microscopy in 93 cases (80%). The FNAC involved lymph nodes in
      57 cases (49%), liver in 27 cases (23%), skin in 22 cases (19%), bone in six
      cases (5%), lung in three cases (3%), and pleura in one case (1%). The neoplasm
      was generally cell typed, and there were 60 adenocarcinomas/poorly differentiated
      carcinomas, 26 small-cell carcinomas (SCC), 23 squamous-cell carcinomas (SQCC),
      and six undifferentiated large-cell carcinomas. The primary source was defined in
      30 cases (26%), consisting of lung in 11 cases, prostate in nine, kidney in four,
      colon in four, pleura in one, and peritoneum in one. Clinical correlation also
      supported a lung origin for the SCC, while the majority of the SQCC in upper and
      middle cervical lymph nodes were considered head-and-neck tumors. Our results
      affirm that FNAC is a viable and simple procedure in MUO investigations.

PMID- 9582564
TI  - Role of touch imprint and core biopsy for detection of tumor metastases in bone
      marrow.
AB  - A total number of 248 bone marrow trephine biopsies were reviewed and 21 paired
      biopsy and touch imprints were identified to estimate the role of these two
      diagnostic methods for detection of tumor metastases from nonhematologic
      malignancies in the bone marrow. The study period ran between January 1, 1993,
      and June 1, 1996. Eight histology sections and eight touch imprints were prepared
      from every case and were reviewed by two pathologists independently. In 20 cases,
      tumor cells were present without a doubt both on cytologic and histologic
      preparations. In one touch imprint, single cells were suspicious for malignancy,
      and the final pathology report was prepared after examination of the histologic
      sections. There was no positive biopsy in which the imprint was negative for
      tumor cells, and no positive touch imprint in which the biopsy was negative for
      such cells. The results from our study show that every one of these approaches
      has advantages and disadvantages and that they have a complementary role for
      identification of solid malignancies in the bone marrow.

PMID- 9582565
TI  - Expression of sialyl-Tn in fine-needle aspirates from mammographically detected
      breast lesions: a marker of malignancy?
AB  - Malignant transformation is frequently associated with abnormal expression of
      cell surface carbohydrates. Sialyl-Tn (STn) is a core carbohydrate antigen of
      tumor-associated mucin formed by the premature 2-6 sialylation of N
      acetylgalactosamine. In an attempt to verify whether this antigen is restricted
      to malignant cells, we studied 30 cases of fine-needle aspiration (FNA) cytology
      from mammographically detected breast lesions. The rationale for choosing this
      material was the acknowledged difficulty in diagnosing cytologically small breast
      lesions, especially epithelial intraductal proliferations. The cases were divided
      in benign lesions (two fibroadenomas and ten ductal hyperplasias) and malignant
      lesions (16 ductal carcinomas). Ten of sixteen malignant cases (62.5%) were
      positive for STn. Five of fourteen benign cases (35.7%) were also positive for
      STn (two fibroadenomas and three ductal hyperplasias). The most consistent
      positive results in benign lesions resulted from cases that displayed apocrine
      metaplasia, although positivity has also been observed in ductal cells without
      metaplasia. We did not find statistical significant differences among STn
      expression in benign and malignant breast lesions detected by FNA (P = 0.14).
      Thus, we conclude that STn is neither specific nor sensitive for detection of
      malignancy in FNA from mammographically detected breast lesions.

PMID- 9582566
TI  - Diagnosing Helicobacter pylori by imprint cytology: can the same biopsy specimen
      be used for histology?
AB  - Imprint cytology of the gastric mucosa has been found to be very simple,
      inexpensive, and rapid for diagnosing Helicobacter pylori infection. However,
      there is a fear that preparing imprint smears may damage the biopsy specimen for
      subsequent histologic examination. This study was planned to investigate whether
      this damage happens. Four antral biopsy specimens were obtained from each of the
      100 patients undergoing upper gastrointestinal endoscopy. Imprint smears were
      made from two biopsy specimens, which were then fixed in 10% formal saline and
      sent for histologic study. The third and fourth biopsy specimens were directed
      fixed in 10% formal saline for histologic examination. Two pathologists examined
      the imprint smears. Agreement between the two observers was observed in 97% of
      cases. Beyond-chance agreement was good with a kappa index of 0.90. H. pylori
      organisms were seen in 82% of biopsy specimens from which imprint smears were
      prepared and in the same percentage of biopsy specimens that were processed
      directly. The pathologists could not identify the histologic sections form which
      imprints were made. It is concluded that imprint cytology is an excellent method
      of diagnosing H. pylori infection and that preparing imprint smears does not
      alter the quality of the tissue. The same biopsy specimen can be used for
      histologic studies.

PMID- 9582567
TI  - Nuclear grooves in fine-needle aspiration biopsies of breast lesions: do they
      have any significance?
AB  - Nuclear grooving is a recognized morphologic feature frequently seen in papillary
      carcinoma of the thyroid. This feature is also occasionally seen in other
      nonneoplastic and neoplastic conditions. Nuclear grooves have been described in
      tubular carcinoma of the breast. However, the significance of nuclear grooves in
      benign and malignant conditions of the breast has been rarely studied. In a
      retrospective study, we searched for the presence of nuclear grooves in
      Papanicolaou-stained and Diff-Quik-stained fine-needle aspiration biopsies (FNAB)
      of 50 cases of primary breast carcinomas, 25 cases of proliferative breast
      disease, and 25 cases of fibroadenoma. In addition, 10 cases of metastatic breast
      carcinoma diagnosed by FNAB were reviewed. Nuclear grooves were identified in 39
      of 50 (78%) of the histologically confirmed primary breast carcinomas and in 9 of
      10 (90%) of the cases of metastatic breast carcinomas in the Papanicolaou-stained
      smears. Nineteen of 50 (38%) of the cases of proliferative breast
      disease/fibroadenoma showed nuclear grooves in the Papanicolaou-stained smears.
      The difference between the percentage of cases showing nuclear grooves seen in
      the Papanicolaou-stained primary breast carcinomas and metastatic breast
      carcinomas compared with the benign breast lesions was statistically significant
      (P < 0.001 in the primary breast carcinoma cases and P < 0.01 in the metastatic
      breast cancer cases). Nuclear grooves were identified less often in the Diff-Quik
      stained smears, and their presence in malignant lesions versus cases diagnosed as
      benign breast disease was not statistically significant. This study suggests that
      although the presence of nuclear grooves is more frequently seen in malignant
      breast lesions, their presence cannot totally exclude the possibility of benign
      breast disease. The presence of nuclear grooves, however, may serve as a
      diagnostic clue in metastatic tumors of unknown primary.

PMID- 9582568
TI  - Multidisciplinary approach to deep-seated lesions requiring radiologically-guided
      fine-needle aspiration.
AB  - Fine-needle aspiration (FNA) is a diagnostic modality that continues to improve
      in accuracy as training and experience accumulate. With increasing operator
      expertise and improved localization techniques, greater numbers of patients are
      able to benefit from FNAs performed on sites that are otherwise difficult or
      dangerous to reach by conventional surgery. We present a retrospective review of
      a 2-yr experience with radiologically-guided deep-seated FNA. In 115 cases
      involving transthoracic and transabdominal sites, we achieved the following
      overall figures: 91.9% sensitivity, 100% specificity, 93.9% diagnostic accuracy,
      100% positive predictive value, and 80.6% negative predictive value. Our results
      are compared to those in other series. When properly applied, FNA of deep-seated
      lesions through image guidance is equivalent to tissue diagnosis obtained by
      laparotomy or surgical procedures. The benefits of FNA with or without core
      biopsy vs. scalpel biopsy are readily apparent when one considers the morbidity,
      cost, turnaround time, and trauma to the patient.

PMID- 9582569
TI  - Fine-needle aspiration of metastatic renal-cell carcinoma masquerading as primary
      breast carcinoma.
AB  - This report details a fine-needle aspiration biopsy performed in the
      investigation of two right breast nodules in a patient with previous history of
      lumpectomy for infiltrating ductal carcinoma in the same breast 3 years before.
      Because the cytology was atypical for a mammary carcinoma and cells did not match
      the morphology of the previous breast carcinoma, a tissue biopsy was recommended,
      revealing the presence of metastasis from a previously silent primary renal-cell
      carcinoma. This report illustrates not only how metastatic lesions in the breast
      can masquerade clinically as a primary carcinoma but also the necessity for the
      cautious approach to interpreting the fine-needle aspiration biopsy of these
      lesions. Furthermore, essential guidelines necessary to distinguish primary from
      metastatic lesions in the breast are presented.

PMID- 9582570
TI  - Diagnosis of systemic lupus erythematosus in an elderly male by pericardial fluid
      cytology: a case report.
AB  - Although pleural and pericardial effusions are common and may rarely be the
      initial manifestation of disease, there are few reports of SLE diagnosed in a
      cytopathology laboratory. We describe an unusual case of SLE in a 75-year-old man
      who presented with cardiac tamponade. Cytologic examination of the pericardial
      fluid revealed numerous LE cells and led to the diagnosis of SLE. This case
      illustrates the importance of careful evaluation of a serous effusion for LE
      cells in patients of either gender and of any age.

PMID- 9582571
TI  - Langerhan cell granulomatosis with unusual FNAC findings.
AB  - An interesting case of a multifocal Langerhans cell granulomatosis in an 18-mo
      old female child is described. The diagnosis was confirmed by fine-needle
      aspiration cytology. The unusual findings at the initial stage of the disease and
      its possible etiopathogenesis are discussed.

PMID- 9582572
TI  - Fine-needle aspiration cytology of columnar-cell carcinoma of the thyroid: report
      of two cases with cytohistologic correlation.
AB  - The columnar-cell variant of papillary carcinoma is a rare tumor of the thyroid,
      associated with aggressive behavior, early visceral metastasis, and a rapidly
      fatal course. In this report we present the fine-needle aspiration cytologic
      findings of two examples of this variant of papillary carcinoma with
      cytohistologic correlation. In the smears, clusters, monolayered sheets, and
      scattered papillary fronds of tumor cells were present. The tumor cells were
      columnar and exhibited overlapping and stratification of the nuclei. In the first
      case the tumoral cells showed round nuclei with finely granular chromatin
      pattern, small nucleoli and vacuolated-appearing cytoplasm. The malignant cells
      in the second case presented oval to elongated nuclei with stippled chromatin,
      inconspicuous nucleoli and indistinct cytoplasmic borders. It is important to
      distinguish this tumor from the common thyroid papillary carcinoma because of its
      much more aggressive behavior.

PMID- 9582573
TI  - Congenital toxoplasmosis: diagnosis by exfoliative cytology.
AB  - Toxoplasmosis, caused by the intracellular protozoan Toxoplasma gondii, has as
      its major routes of acquisition either ingestion (of the cyst or oocyte) or
      transplacental infection (by trophozoites). Transplacental transmission occurs to
      the fetus in utero or to the newborn at vaginal delivery. Maternally acquired
      infections can infect the embryo as early as the 7th week of gestation. It has
      been estimated that 15-17% of maternal infections acquired between the 7th and
      14th weeks of gestation are transmitted to the embryo (Lynfield R, Eaton RB.,
      Teratology 1995;52:176-180.). We present a 7-wk-old white male, delivered at 38
      wk of gestation, who shortly after birth was found to have hepatosplenomegaly and
      anemia; he developed liver failure and ascites with persistent anemia during the
      first week of life. After an extensive, but nondiagnostic, work-up, a
      paracentesis was performed which led to a diagnosis of congenital toxoplasmosis.
      This case demonstrates the utility of exfoliative cytology in determining the
      cause of neonatal ascites, especially of an infectious etiology. To our
      knowledge, this represents the first reported case of Toxoplasma gondii diagnosed
      by exfoliative cytology in a pediatric patient.

PMID- 9582574
TI  - Cytology of sex cord tumor with annular tubules: a case report.
AB  - The cytologic findings of a sex cord tumor with annular tubules (SCTAT) that
      ruptured during laparoscopy are described. Features useful in distinguishing
      SCTAT from other ovarian sex cord tumors include the presence of highly cellular
      tubular formations containing well-delimited glassy pink material and absence of
      single cells. To the best of our knowledge, the cytology of SCTAT has not been
      previously reported.

PMID- 9582575
TI  - Pulmonary cryptococcosis and pituitary Cushing's disease.
AB  - Pulmonary cryptococcosis was diagnosed by examining smears obtained by fine
      needle aspiration (FNA) in a patient with pituitary Cushing's disease. FNA
      allowed for rapid diagnosis and prompt treatment of a potentially serious
      infection. The patient fully recovered from her pulmonary disease. Although
      opportunistic infections may occur in patients with endogenous Cushing's
      syndrome, it is rare to see such infections in the subset of patients with
      pituitary Cushing's disease. Hypercortisolism associated with Cushing's syndrome
      appears to induce a transitory immune deficiency state and opens a window of
      opportunity for certain infectious agents such as Cryptococcus neoformans to
      exploit. To our knowledge, this is the third such case reported in this clinical
      setting, and the first diagnosed by FNA.

PMID- 9582576
TI  - Diagnosis of mastocytosis by fine-needle aspiration cytology.
AB  - We report a case of a 28-yr-old man in whom mastocytosis was diagnosed by fine
      needle aspiration (FNA) of enlarged periaortic lymph nodes. FNA cytology revealed
      numerous mast cells characterized by cells having round to oval eccentrically
      placed nuclei and associated coarsely granular cytoplasm, most conspicuous on
      Diff-Quik- and Giemsa-stained smears. Lymphocytes, histiocytes, and occasional
      plasma cells were present in the background. We believe this paper to be the
      first reported case of mastocytosis diagnosed by FNA. The case demonstrates the
      utility of FNA in evaluating lymphadenopathy occurring in mastocytosis.

PMID- 9582577
TI  - Proposed guidelines for primary screening instruments for gynecologic cytology.
      Intersociety Working Group for Cytology Technologies.
AB  - These guidelines were approved by the governing boards of the following six
      societies represented in the Intersociety Working Group for Cytology
      Technologies: American Society for Cytotechnology (ASCT), American Society of
      Clinical Pathologists (ASCP), American Society of Cytopathology (ASC), College of
      American Pathologists (CAP), International Academy of Cytology (IAC), and
      Papanicolaou Society of Cytopathology (PSC). The proposed guidelines as written
      reflect the current status of technologies in early 1997. These guidelines may
      evolve over time as newer technologies are developed.

PMID- 9582578
TI  - Immunohistochemical analysis of gel-transferred cells in cytologic preparations
      following smear division.
AB  - Fine-needle aspirations on solid tumors are used increasingly as a means of
      obtaining a primary diagnosis. In many cases, a panel of immunostains performed
      on these aspirates is necessary to further characterize the cytologic
      interpretation. The amount of material obtained through aspiration, however, is
      often quite limited and is present on few glass slides. Previous studies have
      demonstrated the success of dividing cytologic smear preparations into smaller
      parts that could then be used for a panel of immunohistochemical stains. These
      results, however, did not compare the immunoreactivities of various antibodies
      before and after tissue transfer on cytologic preparations. In the present study,
      41 immunohistochemical stains that employed 16 antibodies on 15 tumor
      preparations were performed following smear partition using the tissue-transfer
      technique. The percentage of cells that stained positive after transfer was
      determined and was correlated quantitatively to the untransferred controls.
      Specific immunoreactivity was demonstrated in 30 of 38 cases (79%) but was
      significantly decreased or lost in 8 of 38 cases (21%), which included antibodies
      for S-100, estrogen and progesterone receptors, chromogranin, neuron-specific
      enolase, and cytokeratin. Morphology was well preserved following tissue
      transfer, although limited cytoplasmic damage was seen in up to 25% of tumor
      cells. Immunopositive samples were found to be easily interpretable. Because
      sporadic cases fail to show immunohistochemical staining reactions following
      cytologic smear division and transfer, negative immunohistochemical stains in
      such preparations should be approached with caution.

PMID- 9582579
TI  - Air-dried/rehydrated CV smears are different.

PMID- 9582580
TI  - Extraneous tissue in cell block sections.

PMID- 9582581
TI  - Intranuclear cytoplasmic inclusions in the differential diagnosis of papillary
      thyroid carcinoma and bronchioloalveolar carcinoma.

PMID- 9582582
TI  - Clonal dissemination of vancomycin-resistant Enterococci and comparison of
      susceptibility testing methods.
AB  - One hundred fifty clinical isolates of Enterococcus faecalis (88 isolates) and
      Enterococcus faecium (62 isolates) were tested in vitro for their susceptibility
      to vancomycin and high-level aminoglycosides (HLA). Remel's Synergy Quad Plates
      (RSQ) were used as the reference method and compared to Kirby-Bauer disc
      diffusion test, Vitek GPS-TA card, MicroScan Panel (GP-6), and Etest.
      Streptomycin susceptibility results for MicroScan GP-6 and RSQ were recorded at
      24 and 48 h and all other methods and antibiotics were read at 24 h or less. When
      compared with the agar screen method, all of the methods demonstrated > 99%
      agreement. One isolate was falsely sensitive to gentamicin at 24 h, but resistant
      at 48 h, when tested on both MicroScan and RSQ agar screen. Thirty-nine isolates
      showed resistance to vancomycin with all methods. These isolates were from three
      different local hospitals and were identified as E. faecium. Pulse-field gel
      electrophoresis demonstrated that all of the vancomycin-resistant isolates were
      derived from the same clone. Of interest is the observation that high-level
      resistance to aminoglycosides varied between the clonally related isolates.

PMID- 9582583
TI  - Candida parapsilosis fungemia associated with implantable and semi-implantable
      central venous catheters and the hands of healthcare workers.
AB  - A cluster of six cases of fungemia among hematology, bone marrow transplant, and
      oncology patients was investigated in a case-control study (18 controls). The use
      of implantable and semi-implantable central venous catheters was significantly
      associated with cases (p = 0.016). The hands of three healthcare workers (HCWs)
      were positive for Candida parapsilosis. Electrophoretic karyotyping showed two
      profiles among patients and HCWs, and five among six unrelated strains. The
      profiles of two HCWs matched the ones of the patients they had handled. The
      patients' strains were moderate or strong slime producers, whereas none of the
      HCWs' were strong producers. In conclusion, our results indicated the occurrence
      of an outbreak C. parapsilosis fungemia related to long-term central venous
      catheters in which the hands of HCWs were implicated. The amount of slime
      production might be associated with the pathogenicity of the strains.

PMID- 9582584
TI  - In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L
      743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other
      filamentous fungi.
AB  - LY303366 and MK-0991 (previously L-743,792) are new echinocandin derivatives with
      excellent broad-spectrum antifungal activity. We investigated the in vitro
      activity of LY303366, MK-0991, itraconazole, amnphotericin B, and 5-flucytosine
      against 51 clinical isolates of filamentous fungi, including Aspergillus flavus
      (10), A. fumigatus (12), Fusarium spp. (13), Rhizopus spp. (6), Pseudallescheria
      boydii (5), and one isolate each of Acremonium spp., A. niger, A terreus,
      Paecilomyces spp., and Trichoderma spp. In vitro susceptibility testing was
      performed using a microdilution broth method performed according to National
      Committee for Clinical Laboratory Standards guidelines. Ly303366 was two- to
      fourfold more active than MK-0991 against A. flavus, A. fumigatus, and
      Trichoderma spp. Both LY303366 and MK-0991 were considerably more active (MIC90
      of 0.03-0.12 micrograms/mL) than itraconazole, amphotericin B, and 5-flucytosine
      against Aspergillus spp., but were less active than intraconazole and
      amphotericin B against Rhizopus spp. MK-0991 was more active than either LY303366
      or intraconazole against Acremonium spp., Paecilomyces spp., and P. boydii. These
      data demonstrate promising activity of both LY303366 and MK-0991 against
      Aspergillus spp. and other species of filamentous fungi that are likely to be
      encountered clinically. Further in vitro and in vivo investigation is indicated.

PMID- 9582585
TI  - A rapid immunochromatographic test (ICT) for diagnosis of Plasmodium falciparum.
AB  - A field study was conducted to assess the sensitivity and specificity of rapid
      immunodiagnostic test based on detection of Plasmodium falciparum histidine-rich
      protein-2 (PfHRP-2) in peripheral blood for diagnosis of P. falciparum infection.
      Evaluation in 173 patients showed that the assay was 98.59% sensitive and 97.1%
      specific. There was no cross-reactivity with P. vivax. The test was positive in
      few patients who were found to be negative by microscopy showing the presence of
      antigen after curative chemotherapy. The test is a valuable diagnostic tool for
      falciparum malaria, especially in emergency/field situations requiring rapid
      diagnosis.

PMID- 9582586
TI  - Urinary pharmacodynamics of low-dose ciprofloxacin and ofloxacin.
AB  - The incidence of resistant uropathogens to the fluoroquinolones is increasing,
      but their effectiveness in the urine against these strains is unknown. In this
      investigation, we studied the urinary pharmacodynamics of ciprofloxacin (100 mg)
      and ofloxacin (200 mg) against urinary isolates that were moderately resistant to
      ciprofloxacin (Escherichia coli, MIC = 4; Klebsiella pneumoniae, MIC = 4.
      Staphylococcus saprophyticus, MIC = 8) and ofloxacin. Seven healthy female
      volunteers received three doses (one dose every 12 h) of ciprofloxacin and
      ofloxacin in a randomized, crossover design with a 1-week washout period between
      regimens. Urine bactericidal activity was determined after the first and third
      dose of each drug. Both ciprofloxacin and ofloxacin exhibited prolonged (> or = 6
      h) urine bactericidal activity against the E. coli and K. pneumoniae isolates
      after the first dose. No bactericidal activity was demonstrated for ciprofloxacin
      against the S. saprophyticus strain. In contrast, ofloxacin exhibited urine
      bactericidal activity for 8 h against this isolate. Similar findings were
      observed after the third dose, with the exception that ciprofloxacin exhibited a
      short period (4 h) of bactericidal activity against the S. saprophyticus strain.
      In summary, low-dose regimens of ciprofloxacin and ofloxacin exhibited prolonged
      bactericidal activity against moderately resistant strains of common bacterial
      uropathogens. Only ofloxacin demonstrated bactericidal activity in the urine
      during the first dosing interval against a moderately resistant isolate of S.
      saprophyticus.

PMID- 9582587
TI  - Detection of methicillin resistance in coagulase-negative staphylococci initially
      reported as methicillin susceptible using automated methods.
AB  - Reliable detection of methicillin resistance in coagulase-negative staphylococci
      (CNS) is required for appropriate therapy of serious infections from these
      pathogens. To determine the most accurate method of measuring methicillin
      resistance in CNS initially reported as methicillin susceptible by automated
      methods, we compared mecA detection by polymerase chain reaction (PCR) with
      phenotypic methods. One hundred eighty-eight blood culture isolates of CNS that
      were initially reported as susceptible to methicillin using commercial methods
      (Vitek or MicroScan) were tested by agar dilution, disk diffusion, oxacillin salt
      agar screen plate, and a multiplex PCR assay using primer sets for mecA and 16S
      rRNA. Sixteen isolates (8.5%) previously reported as methicillin susceptible by
      automated methods contained the mecA gene. MICs of these isolates ranged from 0.5
      microgram/mL to > or = 128 micrograms/mL. Ten of these isolates had MICs equal to
      or below the NCCLS breakpoint of 2 micrograms/mL. Six of the 10 isolates (4 with
      MICs of 0.5 microgram/mL and 2 with MICs of 2 micrograms/mL) did not grow on any
      of the oxacillin screen plates after 48 h of incubation at 30 degrees C or 35
      degrees C. All six isolates were induced to grow in the presence of oxacillin at
      128 micrograms/mL by serial passaging on plates containing increasing
      concentrations of antibiotic. Retesting with MicroScan and Vitek detected
      methicillin resistance in 7 and 10 isolates, respectively. Disk diffusion testing
      with incubation for 48 h proved to be the next best method after PCR for
      detection of methicillin resistance (15 of 16 isolates). Commercial automated
      methods and some methods recommended by National Committee for Clinical
      Laboratory Standards may not detect methicillin resistance in CNS that carry the
      mecA gene and have MICs just below breakpoint.

PMID- 9582588
TI  - Against all odds.

PMID- 9582589
TI  - Joint care admissions to a psychiatric unit: a prospective analysis.
AB  - Despite developments in general hospital liaison psychiatry over the past 20
      years, joint care still remains underdeveloped in Europe. Psychiatry continues to
      move from the mental hospital to the general hospital unit without the parallel
      evolution of combined medical and psychiatric. An inpatient unit that provides
      both medical and psychiatric care may provide an essential integration of care
      that can benefit a select group of patients. The aims of this study were to
      prospectively evaluate the profile, treatment, and follow-up of patients admitted
      to the joint-care unit, and to examine the difficulties associated with the
      treatment of these patients on a joint unit. Eighty-nine patients were admitted
      to the joint care unit over a 6-month period. Their median length of stay was 2
      days (range 1-52 days). Fifty-six (50%) were female. The majority (68) (76%) of
      the group were admitted following acts of deliberate self-harm. The overall
      predominant psychiatric diagnosis was depression (41) (46%). During admission, 23
      (26%) patients were found to have behavioral and psychiatric problems that were
      difficult to manage on the ward. Eleven patients caused difficulties for staff
      relating to the management of their physical illness. Thirty-six (33%) patients
      were referred for further psychiatric inpatient care from the joint-care unit.
      The extra burden of these patients' care was felt to fall on the staff working on
      the psychiatric unit. The joint care unit provided a combined psychiatric and
      medical service. It was used predominantly by patients following acts of
      deliberate self-harm. Joint care allowed a comprehensive assessment and
      initiation of treatment of this patient group as well as a learning experience
      for medical and nursing staff. The inclusion of such a unit is a worthwhile
      consideration in any general hospital psychiatric service, with advanced planning
      easing staff workload.

PMID- 9582590
TI  - Organ transplantation: an ideal that is not feasible.

PMID- 9582591
TI  - Idealization in the liver transplant setting.
AB  - Liver transplant patients in psychotherapy may often be relatively silent about
      their new organs but intensely preoccupied with their medical and psychosocial
      caregivers. An important challenge for the liver transplant recipient is to
      preserve positive relationships with caregivers, and to ward off frightening
      feelings of anger and mistrust that may threaten to emerge. Idealization of
      caregivers is common, and may be ego-enhancing. Any threat to the idealization
      may be hazardous. Three liver transplant cases from the author's psychotherapy
      practice are presented which illustrate this paradigm. The ideas developed are
      readily applicable to current problems involving both psychotherapy and selection
      of transplant recipients.

PMID- 9582592
TI  - Lithium intolerance in a medical-psychiatric population.
AB  - This pilot study was designed to explore the tolerance and efficacy of lithium as
      an adjunctive prophylactic agent when added to maintenance antidepressant
      regimens following an episode of depression in an older medical-psychiatric
      population. In a randomized controlled trial, 27 depressed patients had either
      lithium carbonate or placebo added to their maintenance antidepressant (AD)
      regimen following an index episode of depression. Of 17 patients who received
      lithium carbonate, 76% (13/17) were unable to tolerate this agent for the
      duration of the study because of side effects (e.g., gastrointestinal
      disturbances or tremor). The four patients who tolerated lithium were monitored
      for relapse of depression over a 15-month follow-up period, and one relapsed
      (after a 49-week remission) whereas 60% (6/10) of the placebo patients relapsed.
      Cognitive functioning was stable in the lithium-treated patients who remained on
      therapy. The high rate of lithium intolerance in this study indicates that
      lithium dosing and serum levels must be conservatively managed in this clinical
      population.

PMID- 9582593
TI  - Use of the label "litigation neurosis" in patients with somatoform pain disorder.
AB  - The use of the term "litigation neurosis"--a condition with controversial
      clinical significance--might correspond to the expression for a difficult
      physician-patient relationship. The characteristics of patients with a DSM-III-R
      diagnosis of somatoform pain disorder who had been labeled "litigation neurosis"
      by their physicians were explored. Among 74 patients referred to a pain clinic,
      30% had been labeled litigation neurosis, and among 81 patients referred while
      claiming disability benefits, 19% had been thus categorized. The attribution of
      this label was neither correlated to actually being involved in a claim for
      disability benefits nor to involvement in legal action. Patients who had been
      designated with litigation neurosis were characterized by a lower educational
      level, a higher rate of DSM-III-R major depression, and a much higher frequency
      of personality disorders than patients who were not thus labeled. We postulate
      that the communication style of patients with this constellation of
      characteristics, in particular the presence of psychiatric comorbidity, may have
      engendered a difficult doctor-patient relationship, leading physicians to use the
      label in the absence of objective evidence of litigation or involvement in legal
      action. We agree that the inappropriate use of labels such as "litigation
      neurosis" should be questioned.

PMID- 9582595
TI  - Screening for somatic disease in elderly psychiatric patients.
AB  - An inventory of the indications for laboratory tests, electrocardiography (EKG),
      and chest x-ray films was compiled in 194 elderly patients admitted to a general
      psychiatric hospital. Indications were obtained from data on medical history,
      physical complaints, chronically used medication, and findings of physical
      examination. The therapeutic benefit of tests was also evaluated. When the
      therapeutic value of nonindicated tests was assessed, only routine testing for
      glucose, folic acid, vitamin B12, and testing for urinary tract infection in
      women seemed useful. Furthermore, routine determination of full blood counts,
      certain liver enzymes, creatinine or urea, electrolytes, and thyroid-stimulating
      hormone seemed useful because of the frequency of indications. There were no
      arguments for performing the other evaluated laboratory tests, EKG, and x-ray
      films of the chest on a routine basis in these patients.

PMID- 9582594
TI  - Substance use disorders among inpatients with bipolar disorder and major
      depressive disorder in a general hospital.
AB  - The prevalence and type of substance abuse and dependence were determined for 49
      patients with mood disorders on a general hospital psychiatric unit. A
      standardized diagnostic interview was conducted with a high value of inter-rater
      reliability. This study found that 18.4% of mood disorder inpatients met the
      diagnostic criteria for psychoactive substance use disorders by DSM-III-R.
      Sedatives-hypnotics-anxiolytics was the most common substance use disorder
      (10.2%), followed by alcohol (6.1%). Patients with major depression had a higher
      rate of comorbidity with substance use disorders than did the bipolar disorder
      patients (p = 0.011). The prevalence of sedatives-hypnotics-anxiolytics use
      disorder among major depression patients was 35.7%, which was higher than that
      among bipolar disorder patients (0%). Male patients had a significantly higher
      percentage of substance use disorders than did female patients (p = 0.054).
      Seventy-seven percent of the patients with a dual diagnosis of mood and substance
      use disorder were not diagnosed as having substance use disorders by
      psychiatrists in charge.

PMID- 9582596
TI  - Healing environment in psychiatric hospital design.
AB  - Mental health professionals have long speculated that the physical environment in
      which treatment occurs has an impact on both the treatment process and its
      outcome. The few empirical studies that evaluated the effects of
      psychoenvironmental design have shown encouraging results and demonstrated
      clinically desirable behavioral changes and even reduced psychopathology. In view
      of the concept that architecture is a tool in the therapeutic process, the design
      and execution of the psychiatric hospital in the Chaim Sheba Medical Center at
      Tel-Hashomer, Israel, were conducted by a multidisciplinary team of architects,
      mental health professionals, and administrators. The hospital contains three
      acute inpatient wards and a day care and large outpatient clinic. Its operation
      began in 1991. This paper deals with the merging of "user-friendly" architectural
      and environmental design components that create an integral healing environment.
      The paper discusses the positive effects of specific components on patients and
      staff, and suggests that our model of psychoenvironmental approach to psychiatric
      hospital design can provide an important and effective tool in the pursuit of a
      humane, efficient containment and reduction of severe psychopathology.

PMID- 9582597
TI  - Previous help seeking and motivation to change drinking behavior in alcohol
      dependent general hospital patients.
AB  - To assess the suitability of implementing secondary prevention approaches for
      alcohol abuse and dependence in the general hospital, it is worth examining how
      many problem drinkers are detected in this setting for the first time and whether
      these individuals are motivated to change their drinking behavior. In a
      representative general hospital sample (N = 1167), subjects were detected by a
      two-step diagnostic procedure including screening instruments and a diagnostic
      interview during a period of 6 months on all medical and surgical wards. Of
      alcohol-dependent patients, 38.2% had received no help in their lifetime and
      70.8% did not seek help in the year prior to admission. According to the stages
      of change model of Prochaska and DiClemente the minority (10.9%) of subjects
      detected as alcohol dependent for the first time were not considering changing
      their drinking behavior (precontemplation stage); 84.8% were either in the
      contemplation or action stage. Previous help seeking showed no significant
      relationship with the stages of change.

PMID- 9582598
TI  - Recurrent delirium associated with obstructive sleep apnea.
AB  - I describe a case of recurrent delirium associated with OSA in a morbidly obese
      man. Continuous positive airway pressure (CPAC) therapy alleviated the OSA and
      delirium but was only partially effective in preventing relapses of delirium.
      Gastric stapling helped to secure considerable weight loss with reversal of OSA
      and no further recurrence of delirium.

PMID- 9582599
TI  - Post-traumatic stress disorder following needle-stick contaminated with suspected
      HIV-positive blood.

PMID- 9582600
TI  - The institutional memorial service: a strategy to prevent burnout in HIV
      healthcare workers.

PMID- 9582601
TI  - Erotomania in a case of fragile-X syndrome.

PMID- 9582602
TI  - Anti-malignin antibody evaluation: a possible challenge for cancer management.
AB  - The major problem in the management of cancer is the difficulty of an early
      diagnosis. Clinical signs and symptoms generally appear late in the course of the
      disease. The availability of a non-invasive test which detects a blood molecule
      closely associated with the malignant transformation of the cells could be of
      help in the early detection of cancer. Malignin is a 10 kDa polypeptide located
      in the cytoplasmic and outer membranes of all malignant cells. Anti-malignin
      antibodies (AMAs) are IgM immunoglobulins spontaneously produced by the host
      against the oncoprotein malignin when neoplastic transformation occurs; since
      AMAs are IgM, they can represent an "early" transformation indicator useful for
      the early detection of cancer. Elevated AMA serum concentrations, measured by
      means of TARGET@ reagent, have been demonstrated in patients with a wide spectrum
      of non-terminal active cancers, regardless of the anatomical site and histotype
      of the tumor. The AMA test showed a sensitivity and specificity of 95% on first
      determination and > 99% on repeated determinations, and has been reported to be a
      promising diagnostic tool for the early detection of cancer, as well as for
      monitoring of the response to treatment and possibly for screening of an
      asymptomatic population.

PMID- 9582604
TI  - CA 15-3 and bone scintigraphy in the follow-up of breast cancer.
AB  - By means of the retrospective study of the clinical records of 158 women followed
      for breast cancer, we aimed to evaluate the consequences of a non-systematic
      indication for bone scan (BS) based either on CA 15-3 levels alone or a
      combination of tumor marker levels and clinical criteria. With the first option,
      the negative predictive value was 95% and 82% of the BS would have been avoided.
      With the second option, the negative predictive value was 97% and 59% of the BS
      would have been avoided. Furthermore, the preliminary results of a longitudinal
      study showed that those patients with normal CA 15-3 levels and positive bone
      scans showed a subsequent rise in CA 15-3 levels which frequently became elevated
      with a average delay of 15 months. Omission of systematic bone scans in the
      follow-up of breast cancer patients is likely to lead to a delay in the diagnosis
      of bone metastasis in 3% to 5%, the consequences of which have to be examined
      carefully.

PMID- 9582603
TI  - Reevaluaton of the usefulness of systematic bone scanning in initial staging and
      follow-up of small cell lung carcinoma, taking into account the serum levels of
      neuron-specific enolase.
AB  - The prescription of bone scans (BS) in the initial staging and follow-up of small
      cell lung carcinoma (SCLC) is a traditional attitude. The availability of the
      serum neuron-specific enolase (NSE) assay and budget limitations led us to
      evaluate retrospectively, in 57 patients, the consequences of a more selective
      attitude, namely to perform BS only in those patients with abnormal serum NSE
      levels. Both BS and NSE assays were performed in 47 patients referred for initial
      staging of SCLC; NSE levels were normal in 8 but in 2 of these cases (25%)
      secondary bone localizations with great clinical significance were discovered at
      BS. During follow-up, 59 BS were performed in conjunction with NSE assays; 45 NSE
      levels were in the normal range whereas 17 (38%) corresponding BS were suggestive
      of bone metastases. In conclusion, due to the frequent occurrence of false
      negative results in patients with bone metastases, serum NSE levels proved to be
      useless in the selection for BS of patients suffering from SCLC.

PMID- 9582605
TI  - PSA and bone scintigraphy.
AB  - The authors evaluate the role of prostate specific antigen (PSA) and bone
      scintigraphy in the follow-up of radical prostatectomy-treated and radiotherapy
      treated patients. 784 patients were evaluated by simultaneous PSA assay and bone
      scans. The correlation between PSA levels and extension of bone metastases was
      good. The frequency of extraskeletal metastases was low: only 13 patients had
      soft tissue metastases without bone involvement and 33/138 patients with bone
      metastases had also extraskeletal metastases. The results underline the
      importance of PSA and the possibility to omit bone scan when the PSA level is
      below 8 ng/ml in patients who did not undergo anti-androgenic treatments.

PMID- 9582606
TI  - The diagnostic value of pretreatment serum LDH in patients with limited disease
      small-cell lung carcinoma.
AB  - BACKGROUND: In patients with limited disease SCLC, the overall survival is still
      poor. Therefore, a retrospective study was performed involving 48 patients with
      limited disease SCLC to select a parameter which can identify prognostic
      subgroups at the time of diagnosis. MATERIALS AND METHODS: Follow-up ranged from
      3 to 96 months, during which period 38 patients died. Based on clinical outcome,
      patients were classified into 3 groups: complete remission (CR) (n = 16), local
      recurrence (LOC) (n = 7) and distant recurrence (DIS) (n = 25). Age, gender and
      pretreatment biochemical parameters were correlated with clinical outcome and
      survival. For survival 70 patients staged as having extensive disease (ED) served
      as a control group. RESULTS: No differences in survival were found in patients
      with LOC (14% 2 year survival) and DIS (16% 2-year survival) (p = 0.67). Patients
      achieving a complete remission had a significantly better survival (75% two-year
      survival). LDH was found to be the only significant correlate of both tumor
      progression and survival. All patients with pretreatment LDH levels < 240 U/L (n
      = 13) had tumor recurrence. The survival rate of patients with LDH levels, 240
      U/L (41% 2-year survival) was much better than that of patients with LDH levels >
      240 U/L 8% 2-year survival) (p = 0.0001). No significant difference in survival
      (p = 0.33) was found between patients with LD and LDH > 240 U/L and patients with
      ED and LDH < 400 U/L. Patients with ED and LDH values > 400 U/L showed the
      poorest outcome. CONCLUSION: LDH may be used for the identification of prognostic
      subgroups in SCLC. Patients showing pretreatment LDH levels > 240 U/L have an
      extremely high risk of tumor recurrence, while their survival is poor and
      comparable to that of patients staged as having extensive disease and LDH values
      < 400 U/L.

PMID- 9582607
TI  - Serum CA 15.3, CEA and ESR patterns in breast cancer.
AB  - Serum CA 15.3, CEA and ESR were longitudinally determined in 298 patients with
      breast cancer during postsurgical follow-up and/or therapy. Observation lasted
      until the death of the patient or at least for three years. With regards to
      longitudinal serum markers and ESR curves, four different patterns have been
      identified: pattern I: the markers and ESR stayed at normal levels; pattern II:
      the markers and ESR decreased from a peak level; pattern III: the markers and ESR
      fluctuated widely; pattern IV: the markers and ESR increased steadily. We have
      looked at over all survival (OS) and relapse-free survival ( RFS) versus
      longitudinal CA 15.3, CEA and ESR patterns. Univariate Cox regression analysis
      showed that OS and RFS were significantly associated with all four patterns.

PMID- 9582608
TI  - Bladder cancer monitoring using two novel urinary markers.
AB  - Bladder cancer shows extreme variability in its behavior. Even the superficial
      forms, when surgically treated, are characterized by a high recurrence rate and
      therefore regular and intensive post-treatment monitoring is an important aspect
      of the management of this tumor. The standard follow-up of patients with a
      bladder cancer history is based on cystoscopic examination of the internal
      bladder, which is an invasive procedure causing discomfort to the patient. In
      this context, the availability of a non-invasive laboratory test which measures
      circulating markers associated with bladder cancer could facilitate with
      monitoring of patients and could be of help in understanding the metastatic
      potential of bladder tumors, especially the superficial forms.

PMID- 9582609
TI  - Clinical use of tumor markers in the postoperative management of breast cancer
      patients: new concepts.

PMID- 9582610
TI  - Preliminary serological and immunohistochemical evaluation of the reactivity to
      two monoclonal antibodies against MUC4 mucin.

PMID- 9582611
TI  - Is there any pathogenic role for the anti-endothelial cell antibodies (AECA) in
      autoimmune vasculitis?

PMID- 9582612
TI  - IL-1 alpha, IL-1 beta and psoriasis: conflicting results in the literature.
      Opposite behaviour of the two cytokines in lesional or non-lesional extracts of
      whole skin.
AB  - A still debated question in the field of the cytokine network in psoriasis is
      represented by contrasting data reported on the local amount of IL-1 beta
      amounts, of IL-1 in this dermatosis. In fact previous studies have suggested that
      there were decreased Il-1 alpha amounts at the lesional level but increased
      nonfunctional IL-1 beta concentrations as compared to the non-lesional and normal
      epidermis. However, recent data suggest that IL-1 alpha and, to a lesser extent,
      IL-1 beta amounts, are both increased and biologically active in the epidermal
      cell suspension of lesional psoriatic skin as compared to those of normal skin.
      The data reported in the present paper show that IL-1 alpha levels are decreased
      in psoriatic lesional extracts of whole skin (mean 2.9 +/- 2 pg/mg) as compared
      to non-lesional (mean 6.7 +/- 6.2 mg/mg; p = 0.02) or normal skin (mean 13.8 +/-
      9.4 pg/mg; p = 0.0002). IL-1 alpha concentrations were also significantly lower
      in the non-lesional skin than in normal skin (p = 0.02). In contrast, the IL-1
      beta levels (mean 1.2 +/- 0.74 pg/mg were higher in the lesional samples than in
      the non-lesional ones (mean 0.5 +/- 0.4 pg/mg; p = 0.0004) or in normal skin
      (mean 0.4 +/- 0.2 pg/mg; p = 0.004). No differences in IL-1 beta levels were
      observed between non-lesional and normal skin (p = 0.3). In addition both IL-1
      alpha and IL-1 beta are directly correlated with the disease severity and each
      other. Our data, extending the Il-1 determination to the whole skin, seem to
      confirm the previously reported findings at the epidermis level and provide new
      light on possible interpretation of literature discrepancies.

PMID- 9582613
TI  - Functional associations of CD38 with CD3 on the T-cell membrane.
AB  - CD38 is a multifunctional membrane surface glycoprotein expressed by different
      cells and tissues, including T cells at certain stages of their development.
      Besides its involvement in transmembrane signaling, CD38 play a role in cell
      adhesion processes. Structurally, membrane CD38 was reported as presenting
      lateral associations with molecules involved in recognition and signaling, namely
      with the TCR/CD3 complex in T cells. Here we report that ligation of CD38 by
      agonistic and non-agonistic monoclonal antibodies exerts different effects on T
      cells, the former inducing down-modulation of the associated molecules, probably
      through a protein kinase C-dependent mechanism. This observation supports the
      view that the reduced expression of TCR/CD3 is secondary to interplay with CD38
      mediated signaling, which partially overlaps with the CD3-mediated pathway. CD3
      ligation by monoclonal antibodies leads not only to the expected internalization
      of the TCR/CD3 complex but also to down-modulation of surface CD38. The results
      obtained indicate that CD38 is closely associated with the CD3/TCR complex and
      that co-modulation of CD38 with TCR/CD3 is a critical step in signaling processes
      on T lymphocytes.

PMID- 9582614
TI  - Age-related changes of neuro-endocrine-immune interactions in healthy humans.
AB  - Numerous interactions exist among the nervous, endocrine and immune systems,
      mediated by neurotransmitters, hormones and cytokines. The function of these
      systems shows patterns of circadian rhythmicity and a number of age-related
      changes in the 24-hour hormonal and nonhormonal rhythms have been found in older
      human beings. The aim of this study was to evaluate the presence of altered
      integration among the nervous, endocrine and immune systems in older adults.
      Cortisol, melatonin, thyrotropin-releasing hormone (TRH), thyroid
      stimulatinghormone (TSH), free thyroxine (FT4), growth hormone (GH), insulin-like
      growth factor I (IGF-I) and interleukin 2 (IL-2) serum levels were measured and
      lymphocyte subpopulation analyses were performed on blood samples collected every
      four hours for 24 hours from seven healthy young subjects aged 36-58 years (mean
      age +/- s.e. 45.28 +/- 3.31) and from seven healthy old subjects aged 65-78 years
      (mean age +/- s.e. 68.57 +/- 1.91). There was a statistically significant
      difference between the groups in the observed values of CD20 (total B cells,
      higher in the young subjects, t = 2.48, P = 0.028) and CD25 (activated T cells
      with expression of the alpha chain of IL-2 receptor, higher in elderly subjects,
      t = -2.23, P = 0.045); DR+ T cells were also higher in elderly subjects, T=34.0,
      P=0.01). There was no statistically significant difference in the observed values
      of CD2(total T lymphocytes), CD4 (helper/inducer T cells), CD8
      (suppressor/cytotoxic T cells), CD4/CD8 ratio, CD16 (natural killer cells), HLA
      DR (B cells and activated T cells), TcR delta 1 (epitope of the constant domain
      of delta chain of T-cell receptor 1), cortisol, melatonin, TRH, TSH, FT4" GH, IGF
      I, IL-2. In the group of younger subjects a clear circadian rhythm was validated
      for the time-qualified changes of all the factors studied, with the exception of
      CD16, FT4 and IL-2. In the group of elderly subjects a clear circadian rhythm was
      validated for the nyctohemeral changes of CD2 (with a phase delay of three
      hours), CD8, CD4/CD8 ratio, CD16, CD25 (in opposite phase), cortisol (with a
      phase delay of one hour), melatonin, TSH (with a phase delay of one hour) and GH
      (with a phase advance of one hour). The results of the current study show that
      aging is associated with enhanced responsiveness of the T cell compartment and
      alterations in temporal architecture of neuro-endocrine-immune system.

PMID- 9582615
TI  - Bullous pemphigoid and pemphigus vulgaris: correlated behaviour of serum VEGF, sE
      selectin and TNF-alpha levels.
AB  - BACKGROUND: Recently, we reported that soluble E-selectin (sE-selectin), an
      isoform of the cell membrane E-selectin, an adhesion molecule synthesized only by
      endothelial cells, is significantly increased in sera of the patients with
      bullous pemphigoid (PB) or pemphigus vulgaris. A significant correlation was also
      found between the serum sE-selectin levels and the number of skin lesions,
      suggesting the possible use of this molecule to gauge disease intensity before
      therapy. One of the sE-selectin inducers is tumor nerosis factor-alpha (TNF
      alpha), that is also able to enhance vascular endothelial growth factor (VEGF), a
      strong endothelium activator. OBJECTIVE: On the basis of these observations, the
      present study was conducted to analyze the serum levels of VEGF, sE-selectin, and
      TNF-alpha in 8 patients with BP (age: 82, range 54-87, 7 males, 1 female) and in
      6 patients affected affected with PV (age: 55, range 44-65; 5 males, 1 female)
      and to verify possible correlations between these variables and the disease
      activity, In addition, serum sE-selectin levels were measured over time and
      compared with the serum anti-epithelium antibodies titers. METHODS: The sE
      selectin, VEGF and TNF-alpha levels were measured in the samples by means of
      commercially available ELISA kit. The same samples were also employed to measure
      the anti-epithelium antibody titers. RESULTS: Serum VEGF, sE-selectin and TNF
      alpha levels were significantly correlated each other (p at least < 0.01). All
      three variables were also significantly correlated with the number of lesions (p
      at least < 0.01). Serum VEGF levels were found increased (median = 178 pg/ml,
      range 37-595) as compared to 28 healthy controls (median = 135 pg/ml, range
      18/269, p < 0.05). Also serum TNF-alpha levels were found increased (median = 5.5
      pg/ml, range < 0.1-41.0) as compared to 28 healthy controls (median < 0.1 pg/ml,
      range < 0.1-5.3), p < 0.01). When the patients were observed over time, serum sE
      selectin levels highly correlated with the disease intensity in both dermatoses,
      although with different regression curves. CONCLUSIONS: These data further
      underline the endothelium involvement in these bullous dermatoses and stress the
      possibility of employing sE-selectin as a non-specific follow-up marker of both
      BP and PV.

PMID- 9582616
TI  - Acute endocrine effects of interleukin-12 in cancer patients.
AB  - IL-12, which play a fundamental antitumor role, would be also involved in the
      physiological regulation of neuroendocrine and immune interactions. At present,
      however, there are no data about the endocrine effects of IL-12. This preliminary
      study was performed to investigate the acute endocrine effects of IL-12 in
      metastatic renal cell cancer patients. Each IL-12 injection consisted of 0.5
      micrograms/kg/bw subcutaneously in the morning. The study has evaluated the
      effects of 6 different injection cycles. Serum samples were collected before, and
      4, 8 and 12 hours from IL-12 injection. In each sample, we have measured by the
      RIA method serum levels of GH, PRL, TSH, FSH, LH, T3, T4, cortisol, testoterone,
      estradiol and the pineal hormone melatonin. No significant change occurred in
      TSH, FSH, LH, T3, T4, testoterone and melatonin mean serum levels in response to
      IL-12 administration. In contrast, cortisol, PRL and estradiol significantly
      increased after Il-12 injection. GH also increased in response to IL-12, without
      however, significant differences with respect to the baseline values. This
      preliminary study shows that the acute subcutaneous injection of IL-12 may
      influence the endocrine secretions in humans. In particular, IL-12 would
      stimulate the secretions of cortisol, PRL and estradiol. Therefore, this study
      would further confirm that IL-12 may act as biological response modifier in
      humans, not only on the immune system, but also on the neuroendocrine functions.

PMID- 9582618
TI  - Widening the zone of peri-implant attached gingiva.
AB  - The use of implant systems is a focus of interest nowadays, as an alternative
      method to classical dental prostheses used in partially or completely edentulous
      patients. Such an interest of both the patients and the clinicians seemed likely
      to be due to the opportunity of using fixed prostheses on these implants.
      However, besides its advantages, problems exist regarding the zone of attached
      gingiva around implants, for the vestibular depth has generally been decreased
      because of the excessive amount of alveolar bone resorption. The problem from the
      periodontal point of view is that the periodontal pockets around implants used as
      abutments may turn out to be pathologic pockets and an inadequate and
      nonfunctional vestibular depth will result. In this study, the conventional free
      soft tissue autograft technique was performed around 34 implants in 9 patients in
      whom 40 Branemark implants in total were placed. The postoperative evaluations
      indicated that the decrease in the vestibular depth, due to the shrinkage of the
      keratinized tissue had a negative effect on this surgical procedure. The use of
      acrylic stents after surgery seemed to be a better solution and would give good
      clinical results.

PMID- 9582617
TI  - Melatonin as a new possible anti-inflammatory agent.
AB  - Several experiments have suggested that the pineal hormone melatonin (MLT) may
      regulate cancer growth by exerting both oncostatic and immunomodulating effects.
      In particular, MLT would stimulate the anticancer immunity induced by interleukin
      2 (IL-2). Recent studies seem to suggest that the activation of the inflammatory
      response may counteract the anticancer efficacy of IL-2 immunotherapy because of
      the immunosuppressive action of inflammatory-related cytokines, mainly IL-6. At
      present, it is still unknown whether MLT may influence host immune antitumor
      defences by modulating the inflammatory response. To analyze this hypothesis, we
      have evaluated the effects of a chronic administration of MLT on some of the
      commonly used markers of inflammation, including erythrosedimentation rate (ESR),
      IL-6, neopterin and SIL-2R, in patients with evidence of activation of the
      inflammatory response due to advanced solid neoplasms or auto-immune diseases.
      The study included 14 patients (solid tumors: 9; autoimmune diseases: 5). MLT was
      given orally at 20 mg/day during the dark phase of the day for 7 consecutive
      days. Mean serum levels of IL-6, neopterin and SIL-2R significantly decreased in
      both groups of patients. ESR values also decreased on therapy, without, however,
      significant differences. This preliminary study shows that the pineal hormone MLT
      may inhibit the acute inflammatory reaction. Therefore, because of the
      immunosuppressive section of inflammation-related cytokines, this study could
      suggest that MLT may contribute to the generation of the immune reaction against
      cancer at least in part by removing the immunosuppression related to the
      activation of the inflammatory response.

PMID- 9582619
TI  - Cervicofacial actinomycosis (a case report).
AB  - Actinomycosis is now a very uncommonly diagnosed human disease. Major medical
      centers report approximately one case a year. The pathogenesis of actinomycosis
      is unclear, but trauma provides a portal of entry. The cervicofacial form is the
      most common and usually appears as a chronic swelling with one or more draining
      sinus tracts. For treatment, penicillin in high doses is suggested. This case
      report presents a case of cervicofacial actinomycosis in a 14 year old boy which
      was misdiagnosed for a long time and the treatment of the disease with
      mezlocillin, a new antibiotic in the treatment of actinomycosis.

PMID- 9582620
TI  - A cephalometric comparison of mandibular headgear and chin-cap appliances in
      orthodontic and orthopaedic view points.
AB  - In this study, the clinical effects of two extra-oral orthopaedic appliances were
      compared cephalometrically. Lateral cephalograms of 60 individuals were used in
      this investigation. The study group was randomly divided into three parts as a)
      control, b) mandibular headgear and c) chin-cap groups. The subjects of the study
      group were selected among Class III, low angle or vertically normally growing
      individuals. The total observation period was one year. Results showed that both
      appliances were effective skeletally, but there were some differences between
      them. The results are as follows; chin-cap therapy led to an inhibition in the
      development of the upper face and an effective control of the vertical dimension
      in addition to the posterior positioning of the mandible. Mandibular headgear
      inhibited general growth and development of the mandible and showed an increase
      in lower anterior face height and also, a significant lower molar distalization
      was found.

PMID- 9582621
TI  - Molar distalization with bimetric molar distalization arches.
AB  - The aim of this study was to observe the clinical and cephalometric effects of
      intra-oral distalization with the maxillary bimetric arches. 3 girls and 1 boy
      with a mean age of 13.5 years with Class II skeletal and dental relationship were
      selected. Care was taken to select patients having a normal vertical growth
      pattern. Lateral cephalograms were taken at the beginning and at the end of the
      distalization period, which was approximately 3 months. To observe the distal
      movement, a metal marker was attached to the distal end of the buccal tube of the
      first molar. On each lateral cephalometric radiograph a reference plane
      perpendicular to the occlusal plane and passing through the point Sella was drawn
      to assess the amount of distalization. Cephalometric measurements indicated that
      the upper molars moved approximately 3 mm distally and that the lower incisors
      were proclined.

PMID- 9582622
TI  - Root resorption and pulpal changes due to intrusive force.
AB  - Intrusion has been regarded as a controversial topic in the literature. It is
      apparent from many studies that excessive forces applied in orthodontic treatment
      might lead to undesirable results such as circulatory disturbances, pulp
      degeneration, calcification and even necrosis. This study was performed to
      observe the reaction of pulp and roots following tooth intrusion. Material
      consisted of four first premolar teeth of two adult patients. One premolar of
      each patient was intruded orthodontically and the other premolars were taken as
      controls. The palatal roots of the experimental teeth were cut and examined in
      scanning electron microscope (SEM) and the pulps of the teeth were examined in
      transmission electron microscope (TEM). At SEM examination, root surfaces of
      intruded teeth showed resorption cavities of different diameters and depths. At
      TEM examination, vascular degeneration was the main change in the pulps of
      experimental teeth.

PMID- 9582623
TI  - The ultrastructural examination of gingival fibromatosis.
AB  - Hereditary gingival fibromatosis (GF) is a special type of fibrous overgrowth
      classified as non-inflammatory gingival enlargement. Microscopically, the
      connective tissue consists of coarse collagen bundles and fibroblasts. The
      ultrastructural examination of fibrous gingival hyperplasia reveals that
      fibroblasts phagocyte the mast cell granules and mast cells stimulate collagen
      synthesis which results in hyperplasia. In the ultrastructural examination of
      phenytoin-induced hyperplasia, fibroblasts, phagocytosing mast cell granules were
      also found. Based on these findings, the purpose of this study is to establish
      whether there is a relationship between fibroblasts and mast cells in GF. The
      gingival tissues of 5 patients with GF were examined ultrastructurally. In the
      connective tissue, well-defined bundles of collagen fibres were found together
      with fibroblasts and capillaries. There were mast cells around these capillaries
      which had collapsed lumens. The proximity of the mast cells and fibroblasts may
      indicate that mast cells play some role on collagen synthesis of fibroblasts.

PMID- 9582624
TI  - The evolution of clinical periodontal therapy.
AB  - Periodontal diseases are considered as old as the history of mankind, Magical,
      religious and herbal treatments were demonstrated in almost all of the early
      writings. However, methodical, carefully reasoned therapeutic approaches did not
      exist until the middle-ages and modern treatment with a scientific base and
      sophisticated instrumentation did not develop until the 18th century. Prior to
      the 1950s, diseases were mostly treated by root debridement and the extraction of
      the affected teeth. Until the 1970s, it was primarily the symptoms of periodontal
      diseases that were treated. The goal was radical elimination of the periodontal
      pocket (resective therapy). The means were gingivectomy, flap procedures and
      osseous surgery. The disadvantages were the massive sacrifice of periodontal
      tissues, lack of regeneration and clinically elongated teeth. These
      disadvantages, along with the realization of the importance of aetiologic agents,
      raised questions about the necessity of total pocket elimination, and the control
      of subgingival infection by a thorough scaling and root planing (nonsurgical
      therapy), with and without antibiotics, became a commonly used treatment during
      the 1980s. Comparative longitudinal studies, surgical versus nonsurgical,
      demonstrated that both surgical and nonsurgical therapy result in limited
      regeneration and healing with a long junctional epithelium. The most important
      aspects of today's modern concept of periodontal therapy are causal,
      regenerative, and specific for disease type and severity. Although the
      regeneration of the periodontium can be accomplished with the biological
      principles of guided tissue regeneration and graft materials, compared to
      conventional methods, the restoration of a completely normal periodontal status
      has not yet been achieved. We are about to reach our ultimate goals and
      presently, the more promising research directions for a substantial regeneration
      seems to lie in biological mediators. Although the future of periodontal therapy
      is bright, it is still of critical importance to have a preventive strategy to
      keep individuals healthy beforehand.

PMID- 9582625
TI  - Marginal adaptation of resin in relation to application technique and use of a
      dental adhesive system.
AB  - Class V abrasion, erosion and caries lesions restored with composite resin seem
      to be more susceptible to microleakage, because the gingival margin is usually
      placed in cementum and/or dentine. The purpose of this study was to evaluate the
      microleakage, in vitro, of a dentinal bonding system using a technique of
      restoration with a positive and a negative control. This study was accomplished
      using extracted human teeth and dye penetration technique. The teeth were
      examined for microleakage after one month. It was concluded that in the gingival
      wall of the cavity microleakage was significantly reduced when the dentinal
      bonding agent and composite resin was placed and polymerized incrementally from
      enamel, to cementum.

PMID- 9582626
TI  - Histopathological investigation of the effects of various glass-ionomer cements
      on dental pulp.
AB  - In this study, an attempt was made to examine the effects of 4 glass ionomer
      cements on pulp. For this purpose, 30 incisors from 3 dogs were employed. Glass
      ionomer cements commercially known as Ketac-bond, Kromoglass 1, Vitrebond and
      Logobond WM were administered in Black Class V cavities drilled on the vestibular
      surfaces of the teeth, with zinc oxide/eugenol cement being applied to a control
      group. Teeth were extracted at 7, 30 and 90 days and assessed accordingly. The
      pulpal tissues of the teeth were reviewed under light microscope with respect to
      odontoblastic activity, odontoblast aspiration, fibrosis, vascularization and
      erythrocyte accumulation, presence of inflammatory cells, necrosis, and
      reparative dentine. Various findings were obtained from 4 different glass-ionomer
      cements, which were evaluated according to the criteria stated above; however, in
      no section were inflammatory cells or necrosis encountered. Therefore, none of
      the substances utilized in our study was found to have an excessive toxic effect
      on pulpal tissue.

PMID- 9582628
TI  - A comparative study of the area of the canal space obturated by thermoplasticized
      gutta-percha techniques.
AB  - Two thermoplasticized gutta-percha techniques were evaluated for the percentage
      area of canal obturated by gutta-percha and compared with the lateral
      condensation of gutta-percha technique. All obturation systems were used in
      conjunction with Grossman's sealer. Single rooted teeth were obturated by either
      injected thermoplasticized gutta-percha (Ultrafil), thermoplasticized gutta
      percha with metal carrier (Thermafil) or lateral condensation of gutta-percha.
      There were ten specimens in each group. The teeth were embedded in resin,
      sectioned at 1.5 mm, 3 mm and 4.5 mm from the root apex and examined with a
      stereomicroscope. Specimens filled by Ultrafil and Thermafil contained a
      significantly higher percentage of gutta-percha than specimens filled by the
      lateral condensation technique at every level. However no difference was found
      between Ultrafil and Thermafil. Three lateral condensation specimens showed voids
      at the 1.5 mm section; no voids were detected in specimens filled by Ultrafil or
      Thermafil at any level.

PMID- 9582627
TI  - Salivary protein and some inorganic element levels in healthy children and their
      relationship to caries.
AB  - The levels of salivary proteins and some inorganic elements were measured in
      healthy children who were divided into 3 groups according to dentition. The study
      was prompted by the fact that there have been few studies on salivary composition
      and most of them have measured only a few components in children. Salivary
      protein was determined by the method of Lowry; protein electrophoresis carried
      out as described by Laemli; Na and K concentration was measured by flame
      photometry and Ca, Mg, Cl and P measured colorimetrically using Randox diagnostic
      kits. Significant differences were found between the groups for Mg, Na, total
      protein and some protein bands (obtained by electrophoresis). In all dentition
      groups, there was no significant difference in any of the levels between the
      children with and without caries. Salivary inorganic composition, total protein
      concentration and some protein bands rose linearly with age. Salivary protein and
      all the above inorganic element levels rose linearly with total caries surface
      area (Ds + ds), except for Mg which decreased linearly. Some of the protein bands
      decreased with Ds + ds.

PMID- 9582629
TI  - Marginal distortion of metal-ceramic restorations during the porcelain firing
      procedure.
AB  - The fit of a metal-ceramic casting deteriorates during the firing of a porcelain
      facing. Although many factors have been reported as the cause of these distortion
      phenomena, studies of marginal distortion associated with firing metal-ceramic
      restorations have yielded mixed results. The effect of firing cycles on
      distortion of a metal-ceramic coping was examined on 0.5 mm thick palladium
      copper copings with shoulder marginal finish lines. It was found that the
      distortion produced in the first stage of firing was greater than at other
      stages. The marginal distortion seen on the porcelain veneered margin was not
      significantly different from the distortion on the non-veneered margin. These two
      results demonstrate that thermal contraction stresses due to porcelain
      contraction are probably not the primary cause of coping distortion. The internal
      surfaces of the copings were examined for contamination with porcelain particles
      and porcelain contamination was detected with an energy dispersive spectrometer
      analysis. The distortion produced during the porcelain veneering procedure was
      due to porcelain contamination on the internal surfaces of the copings. A
      convenient method is necessary to remove porcelain from the internal surfaces of
      completed restorations.

PMID- 9582630
TI  - The effect of cyclosporin-A on the ultrastructure of gingival tissue in Behcet's
      disease.
AB  - Autoimmune processes are said to play an active role in aetiology of Behcet's
      disease (BD), which is also known as a multisystem disease. In the treatment of
      this autoimmune disease, cyclosporin A (CyA) is used. Gingival hyperplasia (GH)
      is one of the important side effects that have been observed in some of the
      patients. We aimed to evaluate the CyA-induced gingival hyperplasia in BD
      patients. There were 3 study groups, each having 5 patients. In the first group
      displaying GH, mast cells were located between epithelial cells and in the
      connective tissue. Mast cell granules were in crystalline form and electron-dense
      cored form. Fibroblasts and plasma cells were present in the connective tissue.
      The second group did not display GH and the mast cells were similar to those in
      the first group. The third group, was the control group, in which the mast cells
      were located between the epithelial cells and connective tissue. Mast cell
      granules were in electron-dense cored form. We concluded that the development of
      CyA-induced gingival hyperplasia is determined mainly by individual sensitivity
      to CyA, because although both test groups which received CyA showed an increased
      number and activity of fibroblasts, only one group of patients developed GH.

PMID- 9582631
TI  - A genetic and dermatoglyphic study on periodontitis.
AB  - Periodontal diseases encompass a wide range of disease manifestations and
      processes from the mildest inflammation of gingiva to the most advanced
      destructive periodontitis with loss of attachment, bone tissue and teeth. No
      entirely satisfactory identification and classification exist in periodontitis
      especially for high risk early onset periodontitis (EOP) cases, because of
      insufficient knowledge about the aetiological and host factors and their
      overlapping clinical and laboratory features. In this study, the dermatoglyphics,
      which is a genetic test method, suggesting the modes of inheritances of
      hereditary diseases, was performed on 36 EOP and 20 adult periodontitis (AP)
      patients and 20 periodontally healthy individuals. The diagnostic value of this
      genetic test method, which is the study of the quantitative and qualitative
      characteristics of patterns of ridged skin, and the role of heredity on
      periodontal diseases are discussed.

PMID- 9582632
TI  - Aetiology of denture stomatitis.
AB  - The purpose of this study was to determine the etiologic factors of denture
      stomatitis. Fifteen subjects with clinical evidence of localized simple denture
      stomatitis, fifteen subjects without clinical signs of denture stomatitis, and
      forty-five subjects with clinical evidence of generalized simple denture
      stomatitis were investigated clinically and mycologically. Subjects were
      evaluated according to age, sex, duration of denture usage, smoking habits,
      frequency of denture brushing, overnight denture wearing, pH level of saliva and
      degree of candidal colonization and candidal formation. Salivary samples and
      swabs were taken from the palate and the mucosal surfaces of the dentures
      investigated mycologically in order to identify the yeast colonies. Smears were
      taken from the palate and investigated in order to identify candidal formation.
      No statistically significant relationship was found between denture stomatitis
      and age, sex, duration of denture usage, frequency of denture brushing, overnight
      denture wearing or pH level of saliva. There was however, a statistically
      significant relationship between denture stomatitis and denture hygiene, smoking
      habits, candidal colonization and candidal formation.

PMID- 9582633
TI  - The effect of alloxan diabetes and local irritating factors on gingival
      lymphocytes and plasma cells and serum IgG, IgM and IgA levels.
AB  - A histologic study was conducted in 5 diabetic and 5 non-diabetic albino rabbits
      to determine the effect of experimentally induced diabetes upon the number of
      gingival plasma cells and lymphocytes in the absence and presence of local
      factors, and IgG, IgM and IgA levels of the four groups were compared with each
      other. In conclusion, local factors were primarily responsible for the increase
      of the gingival plasma cells and lymphocytes. There was no statistically
      significant difference between the diabetic and non-diabetic group in the absence
      of local factors. Also, there was no marked difference between the serum IgG, IgA
      and IgM levels of all groups.

PMID- 9582634
TI  - Pulp responses to three dentine bonding agents in dogs' teeth.
AB  - The purpose of this study was to evaluate pulp reactions to cavities treated with
      Scotchbond Dual Cure, Gluma and Tenure dentine bonding agents in four adult dogs,
      at intervals of 7, 30 and 90 days. The reactions were compared with the results
      from a control group in which the cavities were treated with zinc oxide/eugenol
      cement. The results indicated that Scotchbond Dual Cure dentine bonding agent
      caused less pulp reaction than Gluma and Tenure dentine bonding agents. However,
      long-term (90 days) specimens showed that none of these three bonding agents
      caused any severe reaction. The recovery of the pulp and a thick layer of
      reparative dentine formation were found quite significant.

PMID- 9582635
TI  - A comparison of bond strengths of soft denture liners to polymethyl methacrylate
      polymerized by conventional water bath and microwave curing techniques.
AB  - This study compared the tensile bond strengths of soft lining materials
      polymerized by using conventional water bath methods and microwave energy. The
      soft lining materials used in this investigation were heat temperature
      vulcanizing (H.T.V.) silicon material Molloplast-B, and room temperature
      vulcanizing (R.T.V) acrylic material Getz Soft Oryl. The H.T.V. specimens were
      prepared with retention, additional retention and without retention, and the
      R.T.V. specimens were prepared by using bonding agent and bonding agent plus
      retention. All were cured by both conventional water bath and microwave energy.
      Results showed that the mean bond strength of H.T.V. specimens ranged from 9.6 to
      13.12 kg/cm2, while the mean bond strength of R.T.V. specimens ranged from 0.36
      to 1.75 kg/cm2. In both conventional and microwave groups, the specimens prepared
      with retention, additional retention and without retention or using bonding agent
      and bonding agent plus retention did not show any significant difference when
      they were compared separately. But the difference between conventional and
      microwave groups was found significant in both H.T.V. and R.T.V. specimens. It
      showed that conventional water bath technique is better than microwave technique.

PMID- 9582637
TI  - Dental procedures and infective endocarditis: current approaches of cardio
      vascular surgery departments from different centres (Part 1).
AB  - The relationship between dental procedures and infective endocarditis is well
      known. Therefore, in order to prevent infective endocarditis, pre-operative
      antibiotic prophylaxis is recommended. However, a total agreement has not been
      achieved regarding which dental procedures and specific heart diseases require
      prophylaxis. The aim of the present study is to review the latest concepts
      dealing with heart diseases regarding the choice of appropriate antibiotic
      regimen, determination of patients at risk of infective endocarditis and dental
      procedures which require pre-operative prophylaxis. Our review revealed that
      there is still some disagreement regarding the above concepts. We believe that
      dentists, especially periodontists, can play a significant role in the prevention
      of infective endocarditis following dental procedures, by giving more attention
      to the subject and also by alerting the infectious diseases/microbiology
      departments and related medical staff.

PMID- 9582636
TI  - Lymphoepithelial cyst.
AB  - Lymphoepithelial cyst is thought to arise from the entrapment of salivary
      epithelium in lymphoid aggregates during embryogenesis. Such lesions are not
      common. It has been noted that there is a close association between the oral
      mucosal lymphoid tissue and the secretory ducts of minor salivary glands which is
      recognized as "Duct-associated lymphoid tissue" (DALT). A case of
      lymphoepithelial cyst with histologically documented close proximity between the
      excretory ducts of the minor salivary gland and lymphoid tissue in the cyst wall
      suggesting a DALT-like structure is presented.

PMID- 9582638
TI  - Dental procedures and infective endocarditis: current approaches of
      periodontology departments from different centres (Part 2).
AB  - Dental procedures performed in the oral cavity, which normally harbours an
      intensive microflora, can cause bacteraemia and death may result from progressive
      cardiac damage or uncontrollable septicemia. Different approaches to infective
      endocarditis related prophylaxis were found, from periodontology departments from
      different countries. It is our opinion of that, periodontology departments must
      alert related departments regarding the importance of specific bacteria involved
      in periodontal disease in the development of infective endocarditis following
      dental procedures.

PMID- 9582639
TI  - Change in the soft tissue profile during and after orthodontic treatment.
AB  - The aim of the present study is to describe the changes in the Holdaway angle
      during and after treatment with a fixed appliance and to search for any possible
      differences between non-extraction treatment and extraction treatment. Thirty
      five randomly selected Angle Class II. Division I cases with complete records
      before treatment, at the end of treatment, and at time at least one year out of
      retention, were collected. The sample was divided into two groups, one consisting
      of nineteen non-extraction cases and the other group of sixteen extraction cases.
      All cephalometric radiographs were traced on to acetate film and a computer
      program developed for cephalometric analysis according to the Bergen Technique
      was used to evaluate the radiographs. A computer program was used for the
      statistical evaluation of the data. In conclusion it can be said that no
      significant differences with regard to the Holdaway angle were found between
      fixed appliance therapy with or without extraction. A significant influence on
      the Holdaway angle itemed from the sagittal base relation (ANB) and chin
      prominence. It seems reasonable to assume that only orthopaedic appliances that
      influence sagittal base relationship, and especially the lower jaw, can have a
      profound influence on Holdaway angle.

PMID- 9582640
TI  - Cephalometric evaluation of maxillary retrognathism cases treated with FR-3
      appliance.
AB  - The purpose of this investigation was to evaluate the efficiency of the FR-3
      appliance on functional Cl III malocclusion cases. A total of 45 functional Cl
      III cases were chosen from a general clinic intake of which 25 were treated with
      the FR-3 appliance and 20 were untreated and were taken as a control group.
      Patients that were treated with FR-3 had the following characteristics: Cl III
      with maxillary deficiency; functional anterior cross-bite; absence of anterior
      open-bite; patients in mixed dentition. The mean age in the treatment group was
      8.4 years 8.8 years in the control group. The observation period was one year for
      both groups. The results were as follows: Sagittal forward growth stimulation was
      not observed in the maxilla. Mandibular growth was redirected in the vertical
      direction. The SNB angle decreased in that the mandible rotated downward and
      backward. The ANB angle increased. There was an increase in total and lower
      anterior facial height and reduction in the overbite. Another skeletal change
      observed was the increase in the cranial flexure angle. Improved dental results
      were a significant amount of overjet increase and a decrease in the IMPA. There
      was also a beneficial effect on the soft tissue profile.

PMID- 9582641
TI  - Cephalometric evaluation of Haas and Hyrax rapid maxillary appliances in the
      treatment of the skeletal maxillary transverse deficiency.
AB  - Two different rapid palatal expansion appliances were compared, using lateral
      cephalograms, anterio-posterior cephalograms and diagnostic models. The Haas
      appliance was used on ten patients and the Hyrax appliance on another ten. A
      difference in the effect of the two appliances was found only for the increase in
      intermolar distance. This difference could be the result of the different
      appliance design.

PMID- 9582642
TI  - Distribution of class I and class II amalgam restorations in Benin City--Nigeria.

PMID- 9582643
TI  - Ameloblastoma of the jaws in Africa.

PMID- 9582644
TI  - Removal of fixed prostheses using ultrasounds and reactor.

PMID- 9582645
TI  - Contemporary cosmetic dentistry. Where do we go from here?

PMID- 9582646
TI  - New automatic handpiece takes the guesswork out of endodontic preparation.

PMID- 9582647
TI  - Starting into implants? An easy bet! Be safe--not sorry!

PMID- 9582648
TI  - "The palatal roll". Soft tissue ridge augmentation using a subepithelial
      connective tissue pedicle graft.

PMID- 9582649
TI  - The posterior all-ceramic crown: the Holy Grail of dentistry?

PMID- 9582650
TI  - Periodontally sound margins in six minutes per veneer.

PMID- 9582651
TI  - Managing malrelated arches and limited vertical space for implant-supported
      overdentures: a case report.
AB  - Advancements in implant therapy have expanded the prosthetic options available to
      treat edentulous patients. The dental professional must be able to accurately
      diagnose the status of the intraoral environmental in order to provide the
      patient with appropriate treatment and a suitable restorative result. Skeletal
      relationships, arch malalignment, implant angulation, and ridge morphology must
      be evaluated during initial treatment planning and incorporated into the
      definitive prosthetic result. This case report demonstrates the application of an
      implant-supported prosthesis to address the various complications presented in
      the treatment of edentulous patients.

PMID- 9582652
TI  - Multidisciplinary implant dentistry for improved aesthetics and function.
AB  - Functional and aesthetic restorations that involve implant-supported prostheses
      rely on the efforts of a multidisciplinary team composed of surgeon,
      prosthodontist, and laboratory technician. The team must examine the anticipated
      restorative site to determine the suitability of existing hard and soft tissues
      for implant placement. When the site requires osseous or gingival augmentation,
      the team must select the appropriate means of restoration from the armamentarium.
      This article describes chronologically the various parameters that must be
      considered by each member of the team as the treatment proceeds.

PMID- 9582653
TI  - Adaptation of a fiber-reinforced restorative system to the rehabilitation of
      endodontically treated teeth.

PMID- 9582654
TI  - The role of physical therapy in dentistry.

PMID- 9582655
TI  - The achievement of aesthetic implant restorations.

PMID- 9582656
TI  - Vertical dimension and freeway space in implant prosthodontics: components of
      macroaesthetics.
AB  - The concept of prosthesis-directed implant-supported restorations in now fully
      recognized, increasing the importance of prosthodontics in the initial treatment
      planning. This article reviews the role of prosthodontics in planning and
      execution of the restoration, with focus on the vertical dimension and freeway
      space--the major components of macroaesthetics. The signs of ridge resorption and
      ridge extrusion are identified, and the methods of ridge correction are
      presented, including alveolectomy prior to fabrication of the prosthesis and the
      adjustment of the abutment height to the modified ridge.

PMID- 9582657
TI  - The function of mastication: implications for occlusal therapy.

PMID- 9582658
TI  - Reconstruction of the posterior maxilla following total loss of crestal bone
      support.

PMID- 9582659
TI  - Restoration of endodontically treated teeth: review, classification, and post
      design.
AB  - Restoration of endodontically treated teeth requires knowledge of material
      science, defect analysis, force analysis, and mechanical engineering principles
      of preparation and design. This article reviews the basic principles of the
      restorative concepts and presents an approach to restoration of teeth, based on a
      new classification. The component strength, component interface strength, and
      analysis of force intensity, frequency, and direction are discussed; the
      restoration design is reviewed, including post selection and passive engagement
      posts. A new post of a "segmentally parallel" design is introduced.

PMID- 9582660
TI  - An immediate-extraction anterior single-tooth replacement utilizing a fiber
      reinforced dual-component bridge.
AB  - Replacement of a single anterior tooth is an extremely challenging procedure.
      Numerous objective and subjective factors must be evaluated by the
      interdisciplinary team in the determination of the appropriate restorative
      method. This article reviews the restorative options and describes an emerging
      treatment modality--the fiber-reinforced dual-component bridge--as the option
      selected in a case requiring an immediate extraction of the maxillary right
      central incisor. The pertinent technology, indications, contraindications, and
      current clinical technique of dual-component nonmetallic prostheses are examined.

PMID- 9582661
TI  - Establishing soft tissue integration with natural tooth-shaped abutments.
AB  - The disparity in dimensions between implant fixtures and the exposed extraction
      sockets has resulted in the development of anatomically shaped abutments. Systems
      have been recently introduced that facilitate the fabrication of abutments to the
      configuration of natural teeth in the anterior maxilla. These systems permit
      development of an aesthetic emergence profile and contours for easy access in
      maintenance of oral hygiene of maxillary anterior single-tooth implant-supported
      restorations. The rationale for the development, indications, advantages, and
      clinical utilization of a recently introduced abutment system is discussed.

PMID- 9582662
TI  - Current clinical concepts for adhesive cementation of tooth-colored posterior
      restorations.
AB  - The adhesive luting of tooth-colored posterior restorations has long been
      considered an unreliable clinical procedure. The physical and clinical properties
      of former base lining materials, the absence of an effective peripheral
      biological seal during provisionalization, and the use of less than optimal
      adhesive systems and luting cements have prevented the achievement of
      satisfactory clinical results. This article describes effective procedures for
      adhesive cementation based on the application of distinctive layers and the use
      of densely filled, viscous luting materials.

PMID- 9582663
TI  - Papilla regeneration by noninvasive prosthodontic treatment: segmental proximal
      restorations.
AB  - Bonded segmental proximal restorations, whether direct or laboratory fabricated,
      can be added to selected aspects of a tooth utilizing the acid-etch technique
      with no macromechanical preparation. When properly executed the prosthetic
      supplements guide and support newly regenerated papillae in deficient
      interproximal aspects. Although they are overcontoured, the properly finished and
      polished convex intracrevicular areas of the restorations will not have adverse
      effects on the tissues. When overcontoured restorations are limited in the
      interproximal space, compression and relief of the gingival fibers results.
      Alternately, any overcontouring of the labial aspects might stretch and cause
      overtension to the gingival fibers and result in iatrogenic damage to the
      periodontal support structures. The controlled, intentional, overcontoured
      proximal restorations and the adjoining soft tissues can easily be maintained
      through regular oral hygiene measures, for healthy, long-lasting service.

PMID- 9582664
TI  - Preventive dentistry.

PMID- 9582665
TI  - Aesthetic evolution of anterior maxillary crowns: a literature review.
AB  - The aesthetics of anterior maxillary restorations and health of the surrounding
      tissues are primary determinants of the successful outcome of a clinical
      procedure. Various restorative materials and application techniques have been
      developed to achieve optimal aesthetics. While early porcelain-fused-to-metal
      restorations exhibited metal margins, the development of shoulder porcelain
      margins in the 1980s resulted in a significant aesthetic improvement. Only in the
      1990s, however, did all-porcelain restorations finally achieve the strength and
      complete range of optical characteristics exhibited by the natural dentition.

PMID- 9582666
TI  - Analgesics in dentistry.

PMID- 9582667
TI  - Tooth fragment reattachment: an alternative for restoration of fractured anterior
      teeth.
AB  - The development of advanced adhesive systems has made it possible to bond various
      substrates, e.g., composite resin and vital or nonvital tooth structures. The
      management of coronal and coronoradicular fractures in the maxillary region with
      these adhesive materials is easier, safer, and more efficacious than the use of
      traditional treatment alternatives that involve the use of posts and cores and/or
      other mechanical devices to obtain retention. Ability to bond the dislocated
      segment of the fractured tooth constitutes a significant step forward in the
      management of this clinical condition.

PMID- 9582668
TI  - Improved shape and emergence profile in an extensive ceramic rehabilitation.

PMID- 9582670
TI  - Periodontal regeneration. A review of periodontal attachment and guided tissue
      regeneration.

PMID- 9582669
TI  - The use of magnification in endodontic therapy: the operating microscope.
AB  - Clinicians have recognized that the use of magnification can improve the
      performance of dental procedures. Of the various magnification systems available,
      loupes have been the most popular, yet their magnification is limited. This
      article reviews and describes the function and clinical application of the
      surgical operating microscope (SOM), emphasizing its utilization in endodontic
      treatment. Several cases are presented to document the clinical procedure and to
      illustrate the difference between operative procedures performed without
      magnification and those completed using the SOM with micromirrors.

PMID- 9582671
TI  - Sorting through a disaster.

PMID- 9582672
TI  - Infant care.

PMID- 9582673
TI  - Topical fluorides.

PMID- 9582674
TI  - GA to sedation. A smooth conversion?

PMID- 9582675
TI  - Profile of periodontal conditions in selected West Malaysian adults.
AB  - To obtain the profile of periodontal conditions in West Malaysian adults, five
      small scale surveys were carried out on selected occupational adult groups, 20-54
      years old, between 1987 to 1990. Periodontal assessment was made using the CPITN
      index. In all, 779 subjects were examined. Results indicated that only 16% of the
      adults examined had healthy gingivae. Bleeding of the gingivae was limited to the
      younger (20-24 years) age group. Calculus is highly prevalent in at least 65.5%
      of all the subjects examined. Periodontal pockets were limited to mostly shallow
      pockets and the risk of developing pockets increased with increasing age. Both
      navy personnel and factory workers showed a higher number of healthy sextants
      across all ages as compared to the other three occupational groups; viz., rubber
      tappers, villagers and government workers. The rubber tappers were the only group
      with deep pockets, with the prevalence ranging between 8 to 25%. Implications of
      the findings to the Malaysian dental delivery system are discussed.

PMID- 9582676
TI  - Salivary contamination and post-cured resin/resin lute bond.
AB  - A previous study has shown that sandblasting and silane priming a post-cured
      inlay resin gave a secure bond to dual-cure luting resin. To determine the
      influence of salivary contamination 4 additional groups of 15 post-cured resin
      discs were mounted in acrylic cylinders, their faces sandblasted with 50 microns
      alumina and silane primed. Surface treatments with saliva (sa), air/water spray
      (a/w), phosphoric acid gel (pa), and silane (si) followed in the order listed: A)
      control, no further treatment; B) sa, a/w; C) sa, a/w, si; D) sa, a/w, pa a/w; E)
      sa, a/w, pa, a/w, si. A 3.9 mm diameter column of dual-cure resin lute was then
      bonded to the dry stored in water surfaces. Specimens were stored in water for 2
      weeks after which the dual-cure resin columns were sheared off the post-cured
      resin discs. Shear bond strengths were A) 19.2 +/- 3.7, B) 17.4 +/- 3.9, C) 16.7
      +/- 3.1, D) 15.6 +/- 3.5, E) 15.4 +/- 2.3 MPa. One-way ANOVA and Duncan's
      Multiple Range Procedure showed groups D and E to be significantly lower than the
      uncontaminated control group A (p < 0.05). There were 2 adhesive failures in
      group B and all others were cohesive within the post-cured resin discs. This
      implies that air/water alone after salivary contamination is an unreliable
      cleansing method. The low shear bond values for Groups D and E may have been
      related to inadequate clearance of the phosphoric acid gel. It was concluded that
      salivary contamination adversely affected the quality of the bonds studied and
      decontamination using phosphoric acid gel resulted in significantly reduced shear
      bond strengths.

PMID- 9582677
TI  - Management of the adult orthodontic patient with removable appliances: factors to
      consider.
AB  - Orthodontic treatment for the adult patient is different from the child. It can
      be either comprehensive in scope or limited in its objectives (adjunctive
      orthodontic treatment). Adjunctive treatment is often within the scope of the
      general dental practitioner and can be of considerable importance in the
      management of adults with periodontal disease and restorative needs. An overview
      of the factors that are related to the treatment of adult patients are presented.
      A few suggestions on better patient management are also included.

PMID- 9582678
TI  - Copper electroplating of non-aqueous elastomeric impression materials: a
      subjective appraisal of their platability.
AB  - Electroplating of non-aqueous elastomeric impression materials is a well
      documented technique. Electroplated silver or copper plated dies have many
      clinical advantages compared to other die systems. Silver electroplating appears
      to be used more frequently than copper electroplating. Utilization of silver for
      electroplating requires an appreciation of financial and biohazard
      considerations. Research on compatibility of copper electroplating with current
      non aqueous elastomeric impression materials is lacking. Samples of currently
      used non aqueous elastomeric impression materials were used to register
      impressions of conventional crown preparations on a typodont. These impressions
      were electroplated to form copper plated dies. The surface qualities of the dies
      were evaluated. Not all impression materials produced visually acceptable or
      workable copper plated dies.

PMID- 9582680
TI  - Diabetic erythroleukemia with sequestra formation in the oral cavity--a case
      report.
AB  - A case report of sequestra formation in the oral cavity most probably as a
      sequelae of periodontal abscess in a diabetic patient is presented. The sequestra
      probably formed as a complication of uncontrolled diabetes mellitus rather than
      erythroleukemia. The lesion was located at the bifurcation area of the lower left
      second molar. Removal of the sequestra, scaling and a course of antibiotics
      managed to control the lesion.

PMID- 9582679
TI  - Bullous pemphigoid--management of a patient with oral and skin lesions.
AB  - A case of bullous pemphigoid with extra-oral and intraoral lesions in a 60-year
      old female is reported. Diagnosis is based on histopathology and direct
      immunofluorescence, and the treatment regime described included oral prescription
      of prednisolone and topical application of a mixture of fluocinonide ointment and
      triamcinolone acetonide in Orabase on the oral lesions.

PMID- 9582681
TI  - Interocclusal distance in patients with different skeletal patterns.
AB  - A pilot study was conducted to measure the interocclusal distance in patients
      with class I, II and III skeletal patterns. Ten patients were randomly selected
      for each skeletal pattern group. The measurements of interocclusal distance were
      obtained from lateral cephalometric radiographs of each patient. The results
      indicated that there was a significant difference (p < 0.05) between the
      interocclusal space of skeletal class II and class III patients.

PMID- 9582682
TI  - Oral pyogenic granuloma (excluding pregnancy tumour)--a clinical analysis of 304
      cases.
AB  - A clinical analysis of 304 cases of pyogenic granuloma (excluding pregnancy
      tumour) were obtained from the clinical evaluations submitted by clinicians while
      sending specimens for biopsy. The average age of the patients with pyogenic
      granuloma was 28.9 years with a peak age incidence in the second decade. More
      female patients were affected and the lesions present mainly in the Chinese. The
      majority of the lesions were ulcerated and pedunculated. The lesions had a mean
      diameter of 10.8 mm with a mean lesion duration of 6.0 months. The gingiva was
      the prevalent site for these lesions with a greater number being located in the
      maxilla. The recurrence rate was found to be 14.1%.

PMID- 9582683
TI  - Cross-infection control in Malaysian dental practice.
AB  - A questionnaire survey on cross-infection control was conducted among 1371
      professionally trained dentists whose names appeared in the Malaysian Government
      Gazette of 1990. A 73.1 percent response rate was obtained. About 13 percent of
      the dentists routinely did not wear gloves during treatment of patients as
      opposed to 54 percent who routinely did. About 83 percent and 52 percent of
      dentists wore a mask and eyewear or glasses respectively when carrying out dental
      procedures. About 93 percent of dentists would use a new sterile needle for each
      patient and about 40 percent would wipe working surfaces with disinfectant after
      each patient. The practice of sterilizing handpieces was found to be uncommon as
      opposed to the sterilization of hand instruments. Variations were observed in
      some of the infection control measures by gender, seniority in service and
      employment status. More than one-third of the respondents had experienced
      puncture wounds during the last month prior to the survey.

PMID- 9582684
TI  - Correlating Streptococcus mutans counts in saliva with plaque amount, gingival
      inflammation and caries experience in school children.
AB  - Samples of stimulated whole saliva were obtained from ninety-four 12-14-year-old
      school children living in inner London to evaluate if there was a correlation
      between Streptococcus mutans counts in saliva with plaque amount, gingival
      inflammation and caries experience. S. mutans counts were obtained by a dip-slide
      method (Dentocult 'Strip Mutans') in which the count was expressed as 0, 1, 2, 3,
      or 4 based on visual estimation of the colony density. There was no association
      between counts' of S. mutans in saliva with plaque amount and gingival
      inflammation. However, there was a significant trend of increased decayed,
      missing, filled surfaces (DMFS) with increasing S. mutans counts.

PMID- 9582685
TI  - Unicystic ameloblastoma: a late recurrence with pseudo-glandular features. A case
      report.
AB  - A case of unicystic ameloblastoma which recurred after 15 years showing unusual
      histological features is reported. The prominent pseudo-glandular features
      present are described. This case highlights the importance of extensive
      histological examination for more characteristic features of ameloblastoma to
      reach a correct diagnosis.

PMID- 9582686
TI  - Advertising in dentistry--a position paper.
AB  - The limitations on advertising set by current regulations are examined and the
      possible consequences of relaxing these regulation discussed. The opinions of the
      dental profession on this issue, as determined through a questionnaire survey of
      members of the Singapore Dental Association (SDA), are included. Finally, some
      recommendations are made with respect to modifying current advertising laws.

PMID- 9582687
TI  - Cross-infection in dentistry: an appraisal of the control guidelines with regard
      to contamination of dental unit water systems.
AB  - The emergence of the human immunodeficiency virus in the last 10 years generated
      renewed concern over the possibility of transmission of this and other infectious
      agents through dental treatment. In this article, evidence for contamination of
      the dental unit water systems with microorganisms probably originating from the
      dental handpieces during dental operative procedures is presented. The
      significance of this finding in relation to existing infection control guidelines
      is discussed.

PMID- 9582688
TI  - A survey on orthodontics and the dental practitioner.
AB  - A questionnaire was mailed to locally trained Division One dental surgeons. The
      questionnaire was designed to assess the practice of orthodontics, the
      undergraduate orthodontic curriculum in relation to the dental practitioner and
      continuing orthodontic education. The results showed that the undergraduate
      orthodontic curriculum was of limited use to the practitioner and that there was
      a need for a continuing orthodontic education programme. Information pertaining
      to various aspects of orthodontic practice was presented.

PMID- 9582689
TI  - Glutaraldehyde in dentistry--a review.
AB  - The disinfective and fixative properties of glutaraldehyde are now widely
      investigated. Glutaraldehyde is effective against micro-organisms and their
      spores. Recently, studies have shown the effectiveness of glutaraldehyde against
      the HIV virus. 2% glutaraldehyde is now recommended for the sterilisation of
      surgical instruments, operating areas, dental impressions and root canals during
      endodontic therapy. Studies have also shown that glutaraldehyde is an effective
      fixative with minimum side effects, limited penetration and quick acting.
      Pulpotomy studies using glutaraldehyde as the fixative agent produce high success
      rates. The important feature is the vital pulpal tissue at the apical third
      suggesting its limited penetration. The small amounts that get distributed
      systemically are quickly metabolised and excreted in the urine or exhaled as
      carbon dioxide.

PMID- 9582690
TI  - The use of dental services by adult Singaporeans.
AB  - The aims of this study were to assess the rate of dental service utilisation
      amongst the adult Singaporeans and to examine factors influencing their service
      utilisation. 1959 subjects aged between 18-75 years participated in a
      questionnaire survey. Respondents were asked whether they had seen a dentist in
      the past twelve months. It was found that 57% of the subjects had not seen a
      dentist in the past year. The reasons given for non-attendance were "felt it was
      unnecessary" (69.7%), "lack of time" (13.8%), "fear" (5.7%) and "cost" (2.4%).
      The low level of dental awareness appeared to be the major block to utilisation
      of dental services in this population.

PMID- 9582691
TI  - Simply marking dentures in the SAF. Singapore Armed Forces.
AB  - Forensic dentistry is important to the armed forces and denture markers are
      useful adjuncts in forensic dental identification. The dental services in the
      Singapore Armed Forces (SAF) recognise this need and have been marking dentures
      since 1987. The "inclusion method" chosen for marking dentures in the SAF is
      described.

PMID- 9582692
TI  - Immuno-pathological and immunological features of oral precancers.
AB  - Cancer of the oral cavity and oropharyngeal regions constitute about 30% of all
      cancers seen in India, with Trivandrum District in southern India having one of
      the highest incidence. Despite easy accessibility for examination and diagnosis,
      these tumours still cause high mortality, emphasizing the need for better methods
      of diagnosis and more importantly prognosis. Most oral carcinomas initially
      present as premalignant lesions and hence understanding their biology and
      behaviour is vital to the management and control of the disease. This review
      presents some of the clinico-pathological, immuno-pathological and immunological
      aspects of oral precancers.

PMID- 9582693
TI  - Singapore dentists' knowledge, advocacy and utilisation of mouthguards.
AB  - A questionnaire was distributed to Singapore Registered Dental Practitioners,
      seeking demographic details, knowledge of mouthguards in preventing dental injury
      during contact sport, current attitudes to advice and provision to at-risk
      patients. 636 questionnaires were posted and 226 valid replies were received.
      Most dentists believed that mouthguards reduced the prevalence of dental injury
      in contact sports. Undergraduate education was the primary source of dentists'
      knowledge. Seventy-four per cent of respondents actively recommended mouthguards,
      but only 26 per cent made one or more in 1992. Only 3 dentists made more than 10.
      Twenty-eight per cent were comfortable with their knowledge in this area, and 76
      per cent would be willing to assist a public awareness campaign.

PMID- 9582694
TI  - Mouthguards: an easy-to-fabricate element of practice preventive programmes.
AB  - Mouthguards reduce the prevalence of dental injuries in contact sports. All types
      are effective, but those which are closely adapted to the teeth are the best
      retained, most comfortable, and therefore best accepted by sports people. Closely
      fitting mouthguards can be directly adapted in the mouth or laboratory-made on a
      stone model of the dental arch. The mouth-formed types can be fitted without
      professional supervision, but the procedure is often more successful if
      undertaken or supervised by a dental professional. The mouth forming procedure is
      quick and involves little material cost compared to the laboratory-made type.
      These savings can be passed on to patients in the form of lower fees which should
      encourage the widespread acceptance of mouthguards as a cost-effective preventive
      measure. Professionally fitted laboratory-made mouthguards are particularly
      suitable for high risk activities such as boxing, where more specialised
      protection such as a bimaxillary guard is indicated.

PMID- 9582695
TI  - Enhancing the oral health of older adults: recommendations for action.

PMID- 9582696
TI  - Clinical and radiographic presentations of HIV-1 necrotizing ulcerative
      periodontitis.
AB  - HIV-1-associated periodontal diseases have been reported in the literature for
      several years. Criteria for the diagnosis of these diseases have not been
      universally accepted, although there are numerous papers describing the clinical
      entity. These case reports provide clinical and radiographic evidence of a type
      of periodontal disease with bone and soft tissue destruction which differentiates
      it from "conventional" periodontal diseases found in both HIV-1-infected patients
      and those not infected by the virus. It is important, from both diagnostic and
      therapeutic aspects, for clinicians to be able to make this distinction. The
      appropriate use of clinical and radiographic findings is extremely helpful in the
      diagnosis, particularly in the case of defining HIV-1 necrotizing ulcerative
      periodontitis (NUP). Whether the patterns of gingival changes and bone loss
      described in these case reports are specific to HIV-1-seropositive persons or
      rather represent severe immunosuppression requires further investigation.

PMID- 9582697
TI  - Oral care planning and handling of immunosuppressed heart, liver, and kidney
      transplant patients.
AB  - In order to provide dentists with specific guidelines regarding appropriate oral
      treatments for transplant patients, their timing, and the prophylactic steps that
      must be taken in their handling, a two-phase study was undertaken. In the first
      phase, the effectiveness of an initial oral hygiene training and motivation
      program was evaluated by statistical testing of the observed differences in
      gingival overgrowth and plaque and gingivitis scores between a study group and a
      control group, each consisting of 46 heart and liver transplant patients.
      Significantly higher scores were observed in the control group. In the second
      phase, the effectiveness of a set of prophylactic measures was tested in 530
      periodontal treatments and 380 dental treatments, applied in 120 heart, liver,
      and kidney transplant patients who showed no significant complications. It was
      concluded that all transplant patients should be monitored by a dentist, and that
      the recommended procedure is effective in preventing oral treatment
      complications.

PMID- 9582698
TI  - Hospital mouth-cleaning aids may cause dental erosion.
AB  - Maintaining satisfactory oral health in bed-ridden patients often calls for
      special aids, such as moistened cotton swabs. The purpose of this in vitro study
      was to investigate three commercially available swabsticks meant for hospital use
      (Dentiswab, Lemon-Glycerin Swabsticks, and Lemon Glycerine Swabs), and one saliva
      stimulant chewing tablet (Cassisal), regarding their possible erosive effects on
      dental enamel. A bovine enamel model system was used. Specimens were incubated
      for 4 hours in the test solutions made of the products. The results showed
      statistically significant enamel softening caused by two of the cotton swabs
      (Lemon-Glycerin Swabsticks and Lemon Glycerine Swabs). Incubation in the
      solutions made of Dentiswab cotton swabs and Cassisal tablets caused only minimal
      changes in microhardness. Profilometric measurements supported these results.
      Stereomicroscopy and SEM showed distinct erosion in specimens treated with the
      lemon swab solution, while the other two did not cause erosion. Thus, attention
      should be focused on choosing the less erosive products if special mouth-cleaning
      aids are used.

PMID- 9582699
TI  - Oral health of persons with and without dementia attending a geriatric clinic.
AB  - This study of 230 hospital geriatric clinic patients compared the oral health of
      individuals with dementias with that of persons with no dementing illnesses. Data
      collected included dental examinations, subject questionnaires and review of
      hospital records. There were few differences among groups of patients based on
      categorization into groups of those diagnosed with (1) no dementia, (2) dementia
      of the Alzheimer's type, and (3) other dementias. However, there were significant
      differences based on degree of cognitive impairment regardless of dementia
      diagnosis. Those with severe dementia had poorer gingival health and oral
      hygiene, but better self-perceived mouth health. There are numerous limitations
      and inherent difficulties in studies involving persons with dementia, and
      overcoming these in the future will likely require long-term, interdisciplinary
      approaches.

PMID- 9582700
TI  - Concomitant occurrence of hypodontia and supernumerary teeth in a patient with
      Down syndrome.
AB  - Concomitant hypodontia and supernumeraries in a patient suffering from Down
      syndrome are presented. Concomitant hypodontia and supernumerary teeth are
      relatively rare, and this is the first case reported in a patient with Down
      syndrome. A conservative approach to management will be pursued, with the accent
      on oral hygiene reinforcement and prevention.

PMID- 9582701
TI  - The effect of dehydration on parotid salivary gland function.
AB  - Dehydration is common in the elderly, and has been traditionally linked with
      salivary hypofunction. This study examined the effect of dehydration on parotid
      salivary flow rates. Twelve young and 12 older healthy subjects abstained from
      food and fluid intake for 24 hrs (dehydration) and then underwent i.v.
      rehydration proportional to the amount of weight lost. Unstimulated and
      stimulated parotid flow rates, weight, hematocrit and hemoglobin values were
      assessed at baseline and 24 hrs, and 1 hr after completion of rehydration. All
      subjects experienced decreases in weight and increases in hematocrit and
      hemoglobin during dehydration. I.v. fluids caused weight gain and decreased
      hematocrit and hemoglobin, demonstrating that subjects were metabolically
      rehydrated. During dehydration, unstimulated flow rates decreased in young (p <
      0.001) and older (p < 0.001) subjects, and stimulated flow rates decreased in
      young (p > 0.05) and older (p = 0.03) subjects. While flow rates increased with
      rehydration, they remained lower than baseline levels. No age or gender
      differences were detected for salivary data. These findings suggest that
      dehydration may cause decreased parotid flow rates, independent of age in healthy
      adults.

PMID- 9582703
TI  - Inter-relationship among degree of mental retardation, living arrangements, and
      dental health in adults with mental retardation.
AB  - The aim of the present investigation was to study the inter-relationship among
      the degree of mental retardation, the way of living, and dental health in adults
      with mental retardation. One hundred and thirty-two adults between the ages of 21
      and 40 years who were mentally retarded were examined on two occasions, one year
      apart. All subjects had had regular dental care for at least 10 years. The
      clinical examinations included bite-wing radiographs and were made by the same
      dentist. The degree of mental retardation was assessed by a professional
      psychologist. The results show that the degree of mental retardation as well as
      living arrangements are factors influencing the dental health of persons with
      mental retardation. Subjects who were mildly retarded had higher caries incidence
      and caries prevalence compared with subjects with moderate or severe mental
      retardation. From a preventive dental health perspective, special attention
      should be focused on subjects with mild mental retardation who are not living in
      institutions.

PMID- 9582702
TI  - The level of cariogenic micro-organisms in patients with Sjogren's syndrome.
AB  - Sixteen patients with caries-inactive sjogren's syndrome with low parotid
      salivary flow rates (< 0.25 mL/min) and 18 caries-inactive control subjects with
      higher salivary flow rates were compared. Mutans streptococci (MS) and
      lactobacilli (LB) counts were measured by means of Dentocult SM strip mutans and
      LB assays. The group with Sjogren's syndrome displayed higher counts of MS (P =
      0.014) and LB (p = 0.003) when compared with controls. The results of this study
      indicate that patients with caries-inactive Sjogren's syndrome and low salivary
      flow may have higher colonization of cariogenic micro-organisms than healthy
      individuals.

PMID- 9582705
TI  - The physical and adhesive properties of dental cements used for atraumatic
      restorative treatment.
AB  - Atraumatic restorative treatment (ART), a recently reported field dentistry
      technique, involves removal of carious debris using only hand instruments and
      placement of a glass-ionomer cement (GIC) restoration. While small ART-GIC
      restorations are effective short-term replacements for lost tooth form, many
      larger ART-GIC restorations are defective after two years. Presently, resin
      modified GICs (R-M GIC) are available which require no special activation
      equipment and handle easily in field settings. This study measured the
      compressive, tensile, and shear bond strengths to enamel and dentin of a
      conventional ART-GIC (Fuji IX) and two R-M GICs (Fuji Plus and Advance) at a
      powder-to-liquid ratio of 3.6:1. The compressive strengths of the GICs tested
      were significantly different. Fuji IX had the highest compressive strength, and
      Advance had the lowest strength (p < 0.05). The tensile strength of the R-M GICs
      was greater than that of the ART-GIC. Fuji Plus showed the highest shear bond
      strength to enamel and dentin and was significantly different from both Fuji IX
      and Advance. A clinical protocol is presented followed by case reports where the
      ART technique was used for management of acute caries in a modern dental setting.

PMID- 9582704
TI  - Nurses' dental assessments and subsequent care in Minnesota nursing homes.
AB  - Concerns about the quality of care in US nursing homes led to 1987 federal
      regulations mandating a national standardized resident assessment. This
      assessment, or Minimum Data Set (MDS), is performed by nurses on all residents
      and includes items to detect oral health problems. As yet, however, there are few
      data on the utility of these MDS oral health evaluations. In this study, we
      analyzed data from Minnesota nursing homes to determine the prevalence of oral
      health problems ("triggers") requiring dental referral from the MDS, version 1
      (Items L and M). We also analyzed the relationship between these MDS assessments
      and subsequent dental care. Data came from a 1994 Minnesota nursing home dental
      utilization study containing information on 466 residents (dental users and non
      users) sampled from 21 nursing homes. Nurses identified 3.2% of residents as
      having oral debris, 3.0% with broken, loose, or carious teeth, and only four
      (0.9%) residents with gum inflammation/soft tissue problems. Only one resident
      (0.2%) was identified with mouth pain. Regression analyses of data from 135
      residents admitted since 1992 revealed no relationship between the presence of
      MDS "triggers" and subsequent utilization measured in visits/year and gross
      charges/year. Nurses' MDS assessments identified few oral health problems, and
      those problems identified did not translate into dental treatment, raising
      questions about the utility of the current approach.

PMID- 9582706
TI  - Myasthenia gravis: dental treatment considerations.
AB  - Myasthenia gravis is an autoimmune neuromuscular disorder that presents
      challenges for the dental practitioner. Facial and masticatory muscles may be
      involved and complicate dental treatment. Exacerbations of the skeletal muscle
      weakness and fatigability that characterize this disorder can be precipitated by
      certain medications used in dentistry. A review of 47 dental treatment episodes
      in 16 patients with myasthenia gravis was undertaken to identify neuromuscular
      responses to dental treatment and post-dental treatment medical therapy required
      for control of resultant exacerbations of muscular weakness. Neuromuscular
      sequelae occurred in 5 treatment episodes for four different patients. Management
      considerations and drug precautions are discussed.

PMID- 9582707
TI  - Education for geriatric oral health promotion.
AB  - Dentate older adults need to be aware that restorative procedures completed in
      the past do not guarantee their oral health now or in the future. By building on
      the strengths of their current behaviors, the elderly may see change as more
      manageable and may accept it more readily. Educational approaches aimed at the
      edentulous older patient should focus on the need for preventative oral health
      care. Thirty thousand new cases of oral cancer are reported each year, and of
      those, 50% are in patients above the age of 65. Progressive bone resorption,
      decreased nutritional intake, and poor oral health affecting self-esteem to the
      point of withdrawal from social circles can all be avoided through periodic
      assessment and timely intervention. All health care professionals must be
      educated in the role that are required of them as health team members. Initial
      exams of elderly patients should include assessment of not only the patient's
      oral health but also his/her ability to perform oral hygiene. An accurate
      assessment of the patient's needs, desires, and abilities will help to eliminate
      many of the misconceptions that the care provider may harbor. Clinical training
      in more thorough oral exams and in methods of effectively educating patients
      concerning oral health is a prudent step for physicians, physician assistants,
      nurses, and nurse practitioners. Effective educational presentations must be
      tailored to the targeted group of older adults; not all strategies will work for
      all elderly people.

PMID- 9582708
TI  - The relationship of age and gender to fear and anxiety in response to dental
      care.
AB  - The apparent association in the published literature of gender and age with
      dental fear and anxiety is far from consistent or universal. A random, age
      stratified telephone survey of 398 adults was performed in a US metropolitan
      area: Denver, Colorado. Information collected included Kleinknecht's Dental Fear
      Survey (DFS). In addition to total DFS scores, values were also calculated for
      the sums of the five DFS physiologic response items (PATRESP) and 12 DFS fear
      producing stimulus items (DENTSTIM). Tests for reliability of these three scales
      were performed (alpha = 0.804 to 0.936). In this sample population, significant
      age and gender differences were noted. In general, fear and anxiety decreased in
      importance with increased respondent age, with the largest difference noted
      between the 40-50 and 60-69 age groups. Increased fear and anxiety were most
      apparent among younger females (20-30 and 40-50) as compared with older females
      (60 and older). However, among males, the summary variable for physiologic
      response to fear and anxiety did not appear to be age-related. Among the oldest
      respondents (ages 70+), 12.2% did report a "major" response to muscle tension
      when in the dental chair. Females reported more fear of some stimuli associated
      with dental care (e.g., "feeling the drill in the mouth") than did males.

PMID- 9582709
TI  - Complicating mucosal reactions in patients receiving radiation therapy for head
      and neck cancer.
AB  - Radiation mucositis is characterized by erythema, pseudomembranes, and ulceration
      of mucosa in the irradiated field. We present two cases of oral mucosal changes
      in patients treated with radiotherapy in the head and neck region, which included
      mucosal erythema and ulceration outside of the radiated fields. One case was
      confirmed as herpes virus infection, and the other was diagnosed as Sweet's
      syndrome. When mucositis extends beyond the radiation fields, the clinician
      should consider other causes of mucosal inflammation and erythema in order to
      begin appropriate management.

PMID- 9582710
TI  - The International Normalized Ratio as a measure of anticoagulation: significance
      for the management of the dental outpatient.
AB  - Susceptibility to bleeding in the patient treated with coumarin derivatives poses
      difficult management issues for the dentist. Classic monitoring for
      anticoagulation relied on the prothrombin time, but reagent variability issues
      have caused the emergence of the International Normalized Ratio (INR) as an
      alternative, and possibly more reliable, laboratory test for the assessment of a
      patient's anticoagulation status. The literature suggests that an INR range of
      1.5 to 2.5 represents the most appropriate level of anticoagulation for the
      surgical patient. That is, at this INR, some protection is afforded against
      thrombo-embolic events without significantly sacrificing effective post-operative
      hemostasis. Since the patient with an INR value within the recommended range is
      still anticoagulated, he/she is still at risk for post-operative bleeding.
      Adherence to local hemostatic measures--such as pressure, topical thrombin,
      alveolar-placed resorbable sponges, and primary wound closure--offers the patient
      important adjunctive protection against post-operative bleeding.

PMID- 9582711
TI  - Aspiration of a primary tooth in a patient with a tracheostomy.
AB  - Aspiration of a foreign object is uncommon in a patient with a tracheostomy. The
      following case history describes the consequences of failure to diagnose an
      aspirated object and how the aspiration of an exfoliated tooth can occur despite
      the presence of a tracheostomy tube. Dentists play an important role in
      preventing foreign body aspiration in debilitated patients.

PMID- 9582712
TI  - Knowledge, opinions, and practices related to oral cancer: results of three
      elderly racial groups.
AB  - A study of 204 inner-city, senior center participants (ages ranged from 41-96
      years) was conducted to assess their knowledge, opinions, and practices related
      to oral cancer. Participants were either White, African-American, or of Korean
      descent. The interview/questionnaire revealed this cohort to lack correct
      knowledge of the signs, symptoms, and risk factors of oral cancer, and to have
      had risk behaviors associated with oral cancer. Given that oral cancer is most
      frequently diagnosed in those aged 65 years and older, and that this cohort tends
      not to obtain routine preventive oral health care, it is imperative that these
      seniors be educated about the risks associated with oral cancer and their need
      for routine oral examinations.

PMID- 9582713
TI  - Dr. Steven Gordon, DDS, Memorial Lecture. Current state of oral health care in
      institutionalized older adults.

PMID- 9582714
TI  - Practice guidelines and quality: is there a connection?
AB  - Yes! Practice guidelines are clearly connected to quality. To characterize that
      connection adequately, however, is a more formidable task and is the subject of
      this paper. This paper will capture, in a few words, the essence of my
      perspective and experience related to quality issues and then attempt to
      establish a connection between practice guidelines and quality from two
      perspectives: first, by suggesting a series of assumptions that would lead to a
      decision on what should be the focus of an appropriate guideline for an older
      adult, since there are many possibilities and agreeing on assumptions is a
      logical first step; and second, by suggesting a framework for the content of such
      guidelines.

PMID- 9582715
TI  - The development of practice guidelines.

PMID- 9582716
TI  - Dental care in nursing homes: guidelines for mobile and on-site care.

PMID- 9582717
TI  - Developing practice guidelines for institutionalized older dental patients.

PMID- 9582718
TI  - Ethical issues in nursing home care: practice guidelines for difficult
      situations.
AB  - Dental professionals encounter a number of challenging ethical and legal dilemmas
      when caring for nursing home residents. Questions may arise in determining a
      patient's capacity to make decisions, securing consent for treatment, choosing
      the most appropriate from among several treatment options, and when and how to
      use restraints. When securing consent for treatment, practitioners must consider
      both the patient's legal competence and his/her decision-making capacity, and
      adopt roles appropriate to the patient's circumstances. If legal competence has
      been retained but decision-making seems impaired, practitioners must involve
      others in the process of determining appropriate care. The capacity to consent to
      treatment can be assessed by questions designed to evaluate the patient's ability
      to understand relevant information, appreciate the situation and consequences,
      manipulate information rationally, and communicate choices. When faced with a
      choice of several treatment options and patient preferences are unclear or
      unknown, the principle of substituted judgment should be used to attempt to
      provide care in keeping with the patient's values. To maximize patient safety and
      dignity, ten guidelines are presented for the use of restraints to provide dental
      care for individuals with behavior problems.

PMID- 9582719
TI  - A dental school's role in developing a rural, community-based, dental care
      delivery system for individuals with developmental disabilities.
AB  - The long-standing problem of access to dental care for persons with developmental
      disabilities in rural Northern California has been addressed in several
      communities by a unique community-based program. The goal was to create a
      coalition to coordinate dental school resources with those of a consortium of
      agencies to address problems in the local communities. This program established a
      community-based model demonstrating the provision of quality preventive and
      therapeutic dental services to these individuals. Through this program, dental
      care delivery systems were formed in three rural communities involving local
      community dentists and agency personnel. The role of the dental school was: (1)
      to establish and then work with a consortium of hospitals, agencies, dentists,
      and other dental personnel; (2) to train local dental personnel; (3) to establish
      and equip hospital dental facilities; (4) to conduct dental screening and triage
      clinics; (5) to consult with local agencies and dentists; (6) to act as a
      referral center for patients with complex medical situations; and (7) to develop
      and disseminate preventive dentistry training materials.

PMID- 9582720
TI  - Patient satisfaction in a regular and after-hours dental clinic.
AB  - To determine whether financial incentives would have an impact on the quality of
      care, we compared patient satisfaction in a "regular" daytime postdoctoral
      general dentistry clinic and an "after-hours" clinic, using a 14-item mail
      questionnaire to a randomly selected sample of adult patients, stratified by age
      and gender. The providers in both clinics were identical; however, the method of
      compensation was different. When residents treated patients in the regular
      clinic, they were paid a fixed stipend, while the "after-hours" clinic residents'
      compensation was fee-for-service. The percentage of patients giving very
      favorable or favorable responses was high in both clinics. However, the response
      of patients in the "after-hours" clinic was more favorable for total number of
      visits required for care to be completed, management of pain, and politeness of
      receptionists. This study demonstrated that the payment of financial incentives
      to residents did not reduce and may even have enhanced patient satisfaction.

PMID- 9582721
TI  - Growth of an ameloblastoma during pregnancy: opportunity lost?
AB  - A 19-year-old pregnant woman presented with an enlarging lesion in the right
      mandible. She was examined by a general dental practice resident in the hospital
      outpatient clinic and subsequently managed by the resident as an inpatient. Both
      moral and ethical questions arose because of the discovery of the lesion early in
      the patient's pregnancy. Delay on the part of the patient while she contemplated
      termination of the pregnancy, compounded by loss of contact with her, eliminated
      the possibility of removal of the lesion during the second trimester. The patient
      elected to continue the pregnancy, and an en bloc procedure was used to remove
      the ameloblastoma.

PMID- 9582722
TI  - The accessibility of dental treatment to adults with physical disabilities in
      northeast England.
AB  - The study was carried out to gain information about the availability and the
      accessibility of dental services to adults with physical disabilities in
      Gateshead, an industrial town with a population of 199,588 situated in northeast
      England. Questionnaires were sent to all general dental practices to ascertain
      the dental staff's perceptions of the accessibility of their premises, their
      willingness to treat people with disabilities, and the types of treatment
      offered. The main problem for access was caused by stairs and other physical
      barriers within buildings. Lack of portable equipment limited the scope of
      domiciliary treatment offered.

PMID- 9582725
TI  - Special relationships and the duty of good faith and fair dealing: do dentists
      understand these concepts?

PMID- 9582723
TI  - Esthetic overdenture for a patient with possible Seckel syndrome.
AB  - This is a case report of a 21-year-old with possible Seckel syndrome (bird-headed
      dwarfism), micrognathia, microdontia, severe bony undercuts, and periodontal
      disease who sought treatment at a university dental clinic. Treatment included
      extractions, periodontal therapy, retention of premolars with sealants, and
      overdentures with resilient soft liners. A limited review of Seckel syndrome
      literature is included. The modification of existing dental materials and
      procedures required for successful functional and esthetic results are discussed.

PMID- 9582724
TI  - Geriatric dentistry on the Internet: can we reach our elderly patients using
      cyberspace?
AB  - A growing number of older Americans use a computer at home, and half of seniors
      who own computers also own modems that can connect them to online services; 25%
      of seniors with computers communicate with online services. Over 70% of online
      seniors use their computers every day. The dental office can interactively
      communicate one-on-one with current and prospective patients using an electronic
      mail newsletter, a Web page newsletter, an "Ask the Dentist" online service, or
      by making dental appointments online. Dental practitioners can take advantage of
      this online revolution and promote oral health for seniors using these
      technologies.

PMID- 9582726
TI  - Violence toward health care workers. Prevalence and incidence at a large,
      regional hospital in Sweden.
AB  - The aim of this study was to establish data for career prevalence and 1 year
      incidence of work-place violence for major categories of health care workers.
      Three consecutive work environment questionnaire studies at a large Swedish
      hospital provided the basis for the study. Prevalence and incidence rates of
      violence were age and gender adjusted to the Swedish working population.
      Prevalence of violence in the study population was compared to data from a
      national sample of Swedish registered nurses. Incidence of violence in each
      professional group was compared to that of the largest group of hospital
      employees, registered nurses. Standardized prevalence ratios for violence were
      significantly higher for all nursing personnel and physicians, and were highest
      for practical nurses (1.56). Standardized incidence rates ranged from 18/100
      person years for physicians to 31/100 person years for practical nurses. The
      relative risk for violence at work over a 1 year period was significantly higher
      only for practical nurses (1.59) as compared to registered nurses. Nursing
      personnel and physicians were at considerable risk for workplace violence in the
      course of their careers. One year incidence rates were highest for practical
      nurses.

PMID- 9582727
TI  - Painful rib syndrome. A variant of myofascial pain syndrome.
AB  - 1. Painful rib syndrome has many similarities to a new classification of pain
      conditions called myofascial pain syndrome. Both conditions respond well to
      noninvasive, supportive nursing interventions. 2. Painful rib syndrome is
      characterized by pain in the upper abdomen or lower chest, a tender spot on the
      costal margin, and reproduction of pain when pressing on the tender spot or
      trigger point. 3. The most critical intervention is to explain the benign nature
      of the condition, and provide support that the pain is real and can be managed.
      Prognosis is not gender or age specific, but is related to treatment response. 4.
      Employees and their families living and working with pain syndromes need the
      nurses' ongoing support and advocacy. Pain syndromes are difficult to diagnose
      and treatment may not eliminate the pain.

PMID- 9582728
TI  - A conceptual model of occupational health nursing. The resource model.
AB  - 1. Conceptual models provide an important framework for the development and
      implementation of a successful occupational health program. The Resource Model
      incorporates the varied resources available from the worksite, community, and
      professional realms. 2. Although the domain of the client focuses on the
      workplace, the concept of "client" may include individuals in the workplace, as
      well as workers' families, the worksite organization, and the local community. 3.
      Using a collaborative team process, the occupational health nurse is a leader and
      coordinator maximizing resources for the most appropriate and realistic health
      and safety program.

PMID- 9582729
TI  - Cost effective, hospital based occupational health services. Successful program.
AB  - 1. Development of hospital based occupational health service programs focused on
      meeting business needs is a response to declining inpatient utilization rates,
      increasing numbers of physicians, and expanding payer control. 2. Nurse practice
      models using nurse practitioners have demonstrated high quality, cost effective
      care. 3. Responsiveness to meeting both employee client and employer needs is the
      key to successful program development.

PMID- 9582730
TI  - Designing an incentive based health promotion program.
AB  - 1. A health incentive program can be an effective intervention for reducing
      employee population risk and altering health care utilization patterns. 2. An
      incentive based health promotion program rewards employees for performing a
      selected set of behaviors. 3. Collecting supporting data (benchmarking, needs
      assessment, organization data, published data) provides the foundation for the
      health incentive program design. 4. Choose an incentive appropriate to the
      employee population and worksite culture.

PMID- 9582731
TI  - Worksite cholesterol screening and diet education programs.

PMID- 9582732
TI  - The cost of being blue.

PMID- 9582733
TI  - Should students be introduced as NPs?

PMID- 9582734
TI  - An overview of abuse reporting statutes.

PMID- 9582736
TI  - Battling the stigma of depression.

PMID- 9582735
TI  - Prescribing medications for mood disorders.

PMID- 9582737
TI  - Can an herb really help depression?

PMID- 9582738
TI  - Pediatric compliance in combination HIV therapy. Getting it right the first time.

PMID- 9582739
TI  - HPV and cervical cancer. Breaking the deadly link.

PMID- 9582740
TI  - Reducing antibiotic angst. Ensuring that your therapy choice is effective.

PMID- 9582741
TI  - Reducing teen health risks. Steps for reaching your adolescent patients.

PMID- 9582742
TI  - Grassroots glory. Organizing a campaign that works.

PMID- 9582743
TI  - CDC issues new guidelines, but changes are few.

PMID- 9582744
TI  - NPs have always been cost-effective.

PMID- 9582745
TI  - Developing caring connections: mentorship in the academic setting.
AB  - The mentoring connections that we have experienced in our school of nursing have
      eased difficult situations and have promoted self-awareness, personal and
      professional growth, and leadership behaviors. Various circumstances result in
      behaviors reflective of issues of culture, race, self-esteem and knowledge,
      values, ethics, experience, and conflict management. Some of these issues are
      related to oppressed group behavior, inadequate communication and conflict
      resolution skills, lack of exposure to diverse academic and professional
      experiences, and a need to learn management of feelings in effective ways. As
      faculty, administrators, students, and alumni, we struggle with those issues,
      knowing that resolution of them is beyond the traditional modes of teaching
      learning, academic relationships and professional socialization. We wish that we
      and our students and alumni will experience an increased connectedness to the
      school and profession. We also wish that we might, as a result of our mentor
      connections, individually and collectively develop self-determination, self
      esteem and confidence, leadership skills, and inner directness. The Mentor
      Connection Program was initiated in response to these strong wishes and has been
      a motivating framework for the reciprocal growth in us all. As for the future, we
      will continue our research and evaluation studies, refine the matching criteria,
      support and expand the mentoring dyads, strengthen faculty-faculty mentoring
      relationships, and seek funding resources for expansion and research. We are
      seeing the positive effects of active mentoring on students, faculty, and alumni
      on issues related to teaching and learning, support, hardiness, and self
      reflection. Mentors produce leaders. Nursing's collective leadership will, we
      believe, depend to a large extent on our mentoring relationships with each other.

PMID- 9582746
TI  - Bottled water as a source of multi-resistant Stenotrophomonas and Pseudomonas
      species for neutropenic patients.
AB  - Stenotrophomonas maltophilia is an emerging nosocomial pathogen in patients
      rendered neutropenic following cytoreductive therapy for malignancy. The
      identification of sources and routes of transmission of this bacterium is of
      importance in the development of strategies to prevent nosocomial acquisition of
      S. maltophilia. A previous study had shown high rates of faecal carriage of S.
      maltophilia amongst patients with haematological malignancy and, as bottled water
      was consumed by many patients, we determined the prevalence of S. maltophilia in
      both carbonated and non-carbonated commercially available bottled water. Whereas
      carbonated water did not yield bacterial growth, 22 samples of non-carbonated
      products had total viable bacterial counts (at 22 degrees C) ranging between 0
      and 4.9 x 10(4)/mL. Three samples yielded S. maltophilia and a further eight grew
      Pseudomonas species. Isolates of S. maltophilia of both clinical and
      environmental origin were able to survive, or grow, in non-carbonated mineral
      water over a range of pH and temperature values, including refrigeration
      temperatures. We therefore recommend that neutropenic patients should not consume
      non-carbonated bottled mineral water.

PMID- 9582747
TI  - Phase I trials in cancer patients: participants' perceptions.
AB  - There is controversy surrounding the ethics of performing phase I clinical trials
      with cancer patients and limited research concerning patients' attitudes when
      participating in such trials. The aim of this study was to determine how cancer
      patients perceive phase I clinical trials in reference to trial participation and
      trial information received. Cancer patients (n = 28) were interviewed 2-4 weeks
      after consenting to participate, using a questionnaire which contained open and
      closed questions. Responses were analysed using non-parametric statistical tests.
      The results demonstrated that although the majority of patients participated in
      experimental treatment because it offered hope that they might be helped, their
      expectations from the new drug were realistic. Patients found that there were
      benefits related to participating in phase I trials and felt that the amount and
      quality of both nursing and medical care was superior in a phase I trial as
      compared to standard treatment in non-experimental settings. There were varying
      opinions among patients with regard to information giving by nursing and medical
      staff. It can be concluded that phase I trials employing cancer patients can be
      ethical.

PMID- 9582748
TI  - Group cognitive behavioural therapy with cancer patients: the views of women
      participants on a short-term intervention.
AB  - At present many emotionally distressed cancer patients receive no psychological
      intervention. The aim of this paper is to examine and report qualitatively on the
      experiences of a small group of seven newly diagnosed women who underwent a group
      cognitive behavioural therapy (GCBT) programme. The GCBT programme was part of a
      larger piece of research comparing patients' experiences of GCBT with that of
      group social support or no group programme of support. Following the 8-week GCBT
      programme, qualitative analysis of interview data revealed that patients had
      learned the skills required to challenge and solve problems and to use the
      cognitive model and effectively employ behavioural exercises to generate improved
      coping. The results also suggest that a GCBT programme with newly diagnosed
      cancer patients may need to allow cancer patients considerable opportunities to
      ventilate feelings and engage in social support with other patients, this being
      regarded as a highly valuable component to build into a GCBT programme.

PMID- 9582750
TI  - Transition to becoming a leukaemia patient: or putting up barriers which increase
      patient isolation.
AB  - When two or more persons, e.g. nurses and patients, act together interaction
      takes place. The expectations of nurses and their definition of the patient's
      illness status affect their behaviour towards the patient and how they practice
      nursing. The aim of this study was to examine the interaction between adults with
      leukaemia and their nurses and how this interaction affected the individual.
      Grounded theory method guided the data collection and analysis. Four adults with
      leukaemia and their nursing staff were observed for 124 h in a haematological
      ward. The core category emerging from the data was transition--the individual
      passing from one phase to another. This denotes a change in role relations, in
      expectations and in abilities. The individual makes their transition in three
      stages. First, the person seeks out information in the corridors and at the same
      time tries to maintain social status. Next, the patient accepts the disease in
      the confines of their room and feels insecure in a totally new situation and
      role. Finally, the leukaemia patient isolates themselves within the confines of
      the bed, and becomes aware of the leukaemia and its side-effects.

PMID- 9582749
TI  - Treatment choices in advanced cancer: issues and perspectives.
AB  - Treatment choices are difficult in advanced cancer, a disease in which there is
      little chance of a cure and in which the aim of treatment is usually to achieve
      palliation. With the clinical evidence and quality-of-life instruments currently
      available, it may be difficult to decide whether the burdens of cytotoxic
      chemotherapy are outweighed by its benefits. However, in some cancers, such as
      advanced colorectal cancer, there is evidence to demonstrate that chemotherapy is
      justified, with overall benefit to the patient. There are, nevertheless, many
      factors to be considered in the selection of the best possible care for each
      patient. These include the availability of new treatments with improved
      tolerability profiles, resource implications, quality of life and survival
      benefits (and how to assess them), the willingness or otherwise of patients to
      undergo chemotherapy, and information and participation preferences among
      patients. The differing attitudes of health care professionals and groups of
      patients add to the complexity of this issue. Guidelines offer one way of
      promoting the consistent and optimal management of patients with advanced cancer;
      however, individual patient choice will always take precedence over guidelines
      which, by definition, are devised with common needs in mind.

PMID- 9582751
TI  - Survivorship and the cancer follow-up clinic.
AB  - In recent years there has been growing interest in the needs of those individuals
      who have survived cancer. It is now possible to describe the adjustments that
      these individuals will make, predict when such difficulties will arise, and
      identify those most vulnerable to adjustment difficulty. The value of the cancer
      follow-up clinic has also received scrutiny, drawing on work previously
      undertaken in the cancer screening clinic setting. Issues discussed in the
      literature include the purpose of follow-up, the most appropriate health care
      professional to undertake the follow-up clinic, and the financial cost of cancer
      follow-up. There exists an opportunity for cancer nurses at present to develop
      roles in the clinic setting, offering patient-centred and cost-effective
      alternatives to physician-led follow-up.

PMID- 9582752
TI  - Some reflections on clinical supervision: an existential-phenomenological
      paradigm.
AB  - This paper reviews psychotherapy, counselling, and nursing literature related to
      ideas of clinical supervision and attempts to illuminate areas important to
      effective health related practice and specifically palliative care. Included are
      explorations of existentialism, phenomenology, existential phenomenology and
      psychoanalytical concepts. The phenomenological idea of lived experience is
      outlined and the Heideggerian notion of authenticity is explored in context. The
      paper also examines dynamic forces such as hope, trust and personal values that
      might influence clinical supervision design and so inform a framework for
      practice. An existential-phenomenological method of supervision is offered as one
      basis for professional practice. The central recommendation of this paper is,
      however, to identify relevant value and belief systems to direct clinical
      supervision. Nursing models might appropriately instruct approaches to
      supervision. The writer considers the phenomenological idea of the lived
      experiences as a means by which to at once capture the essence of palliative care
      nursing and guide the supervision towards the existential idea of authenticity.

PMID- 9582754
TI  - Kidney Foundation focus.

PMID- 9582753
TI  - Clinical supervision with community Macmillan nurses: some theoretical
      suppositions and case work reports.
AB  - This paper explores clinical supervision undertaken with community Macmillan
      Clinical Nurse Specialists in the UK. The philosophical motor is embedded in a
      Heideggerian existential-phenomenological framework, influenced by
      psychoanalytical thinking as described by Yalom. The discussion is derived from a
      qualitative research study designed to reach the lived-experience of five
      Macmillan Clinical Nurse Specialists. The author explores, in context, issues
      related to authenticity and project. Ideas are linked to contemporary concerns
      with reflective practice. The recommendation of this paper is that clinical
      supervision, through whatever method, reaches the vital experience of nursing
      practice. Realising tacit knowledge has potential to inform professional practice
      through powerful synergies of theoretical ways, understanding and lived
      experience. In addition, nurses might attain the existential idea of a boundary
      experience and so identify constructive ways to address issues arising out of
      professional practice.

PMID- 9582755
TI  - Publish or perish: the inside story.

PMID- 9582756
TI  - Teaching CAPD to the visually impaired.
AB  - The increasing number of patients on CAPD (continuous ambulatory peritoneal
      dialysis) offers multiple challenges to the home dialysis unit. During the last
      year we have changed our nursing practice and have successfully trained five
      visually impaired clients to perform CAPD exchanges utilizing a disconnect system
      without a helper or caregiver. In this article we will discuss the methods we
      used, the assist devices and the patient outcomes in our population. We measured
      our success in terms of peritonitis rate, adequacy of dialysis and lifestyle
      considerations for this population.

PMID- 9582757
TI  - Nocturnal hemodialysis (NHD) adapted to the in-centre setting--a pilot study.
AB  - Nocturnal hemodialysis has proven to be an effective and safe modality with many
      benefits. Using NHD parameters, two in-centre conventional hemodialysis (CHD)
      patients participated in a three-week in-hospital trial to test the viability of
      an in-hospital nocturnal hemodialysis (NHD) program. One RN was responsible for
      the initiation and monitoring of all treatments. In order to objectively measure
      results, we maintained a daily log detailing alarm situations, response time for
      both technical and medical support, and required interventions. Patient and staff
      comments were recorded daily. Miscellaneous problems were also documented. Both
      patients were given quality of life questionnaires and patient satisfaction
      surveys pre- and post-trial. Occasionally, difficulties with machine and vascular
      access problems were encountered. Results revealed that subjectively, both
      patients felt much better on NHD when compared to CHD, however they found that
      their personal lives were adversely affected by their absence from home. Upon
      completion of the trial, the accumulated data was analyzed and recommendations
      were made. It was decided that a staff/patient ratio of 1:3 would be safe
      providing that the physical environment allowed the RN to oversee all functions.
      Due to patient dissatisfaction with treatments six nights per week, it was
      suggested that flexibility with patient scheduling was essential. However, it was
      agreed that six nights per week would be advantageous within a chronic care
      facility offering hemodialysis therapy. To ensure complete medical coverage,
      renal fellow integration within the nocturnal project was recommended. In
      conclusion, we feel that the adaptation of NHD to the in-centre setting is viable
      with the appropriate patient population and physical environment.

PMID- 9582758
TI  - Oshawa General Hospital regional dialysis program: dialysis survey.
AB  - In October of 1995 the dialysis program at Oshawa General Hospital initiated a
      survey that was sent out to all dialysis units across Canada listed in the 1995
      Canadian Organ Replacement Registry. The survey was designed to gather a broad
      range of information on dialysis programs across the country. The overall
      response rate was a positive 54%. The results are broken down into general
      information, clinical practice, education, support services and technological
      issues, with further division into hemodialysis and peritoneal dialysis where
      appropriate. The survey revealed wide variations in practice across the country
      with little standardization even within individual regions.

PMID- 9582759
TI  - [Nursing care plans for renal hospitalized patients infected with antibiotic
      resistant enterococci].

PMID- 9582760
TI  - Defining 'competency' in nursing (Part II): An analytical review.
AB  - The reason for the present uncertainty in defining nursing competency is
      analysed. The prevailing educational philosophy underpinning nursing preparation
      for competence is subjected to a critique. The effect and outcome of this
      philosophy on clinical supervision, PREP and the law are considered in relation
      to nursing competence. It is concluded that because nursing competency is only
      vaguely and broadly defined, preparation and assessment of competency is
      haphazard and unstructured; and hence a potential safety hazard for both patient
      and nurse. It is suggested that the UKCC needs to assume responsibility for
      ascertaining nursing competence; and a four-point framework is proposed for
      setting and testing national standards of nursing competency.

PMID- 9582761
TI  - Social construction of episiotomy.
AB  - This article explores the meaning of episiotomy. A review of the literature
      examines the definition, procedure, perceptions and outcomes of episiotomy to
      create a better understanding for those using or experiencing its practice. The
      article highlights that episiotomy means more than just a cut in the perineum.
      Episiotomy means different things to different individuals and groups, the
      meaning being socially constructed depending on social context, professional
      background and personal experience. It is concluded that midwives need to
      understand what an episiotomy means to women, and that through research midwives
      need to develop their own body of knowledge of childbirth from the viewpoints of
      those who are actually experiencing it.

PMID- 9582762
TI  - Patient participation--a review of the literature.
AB  - This article presents a critical review of the concept of patient participation.
      The concept of patient participation has become widely accepted in contemporary
      nursing practice. It is now part of the vocabulary of professional nurses and has
      been heralded as a means of enhancing decision making and human dignity and
      enriching quality of life. Patient participation in care is emerging as a growing
      movement wherein patients are assuming more responsibility for the prevention,
      detection and treatment of health problems in a manner that supplements or
      substitutes for professional services. The review concludes with some
      recommendations for nursing practice, education and research.

PMID- 9582763
TI  - Self-mutilation: culture, contexts and nursing responses.
AB  - Few papers address the issue of deliberate self-mutilation other than from
      clinical perspectives. This paper advocates a user-perspective and discusses some
      of the issues which might attend such a change. The occurrence of self-mutilation
      is placed within a cultural framework so as to enlarge the debate beyond the
      confines of medical/nursing responses. It is suggested that nurses abrogate their
      attachment to such responses and embrace more collaborative approaches to care.
      In particular, nurses are asked to review their (moral) responses to self
      mutilation, an activity which, too often, has been responded to with scorn and
      derision.

PMID- 9582764
TI  - Consultancy in nursing: roles and opportunities.
AB  - This paper considers the development of consultancy roles within nursing,
      specifically examining internal and external approaches to consultation. As
      consultancy in nursing develops there appear to be two major trends: external or
      independent consultancy where the incumbents focus purely upon this role as their
      'job', and internal consultation where consultancy is seen as an integral part of
      their role and is a subrole of the advanced practitioner. In promoting
      consultancy as a means of developing and enhancing advanced practice, suggestions
      are made for future opportunities for consultancy in nursing and its role in the
      development of nursing practice.

PMID- 9582765
TI  - Project 2000 diplomates' perceptions of their experiences of transition from
      student to staff nurse.
AB  - This paper presents findings from an exploratory study of the transition
      experiences of newly qualified Project 2000 diplomates. A qualitative approach
      was utilized involving in-depth interactive interviews with a sample of 10 staff
      nurses. The data indicate that some aspects of transition were initially
      difficult, but that all those interviewed were enjoying nursing. Similarities to
      the experiences of 'traditionally prepared' colleagues are highlighted by the use
      of phrases such as 'in at the deep end' and 'cast adrift', reflecting the
      practice environment once qualified. Paradoxically initial transition for Project
      2000 diplomates is characterized by a lack of confidence, while their questioning
      approach to practice and a willingness to ask others when unsure ('no bluffing')
      suggests a high degree of confidence. Preceptorship in the context of a
      supportive environment is suggested as a model for easing the transition process.
      A re-evaluation of what an initial preparation course can and should achieve, and
      a re-assessment of the skills and knowledge expected of newly qualified nurses,
      are also indicated.

PMID- 9582766
TI  - A qualitative analysis of the nursing documentation of post-operative pain
      management.
AB  - As part of trust-wide practice development project to improve post-operative pain
      management, a descriptive study was conducted in the orthopaedic directorate of a
      large teaching hospital in the north of England. Sixty-five patients were
      included in this prospective study. Patients were interviewed post-operatively
      about their pain experience, and present and worst pain scores were recorded. The
      nursing documentation relating to pain management was also transcribed and a
      content analysis of this nursing documentation is reported. Findings indicate
      that individual assessment of pain was poorly documented and that the nurses'
      record of the patient's post-operative pain experience differed from the patient
      report. Reliance on pharmacological methods of pain relief was evident and
      interventions to help patients cope with night time pain were rarely documented.
      The results are discussed in light of a theoretical framework for acute pain
      management and current research. Implications for practice are discussed and
      areas for further research are suggested.

PMID- 9582767
TI  - New mothers' experiences of postpartum care--a phenomenological follow-up study.
AB  - The aim of this study is to explore and describe the new mother's experiences of
      postpartum care. It is part of an ongoing clinical longitudinal research project
      studying experiences of health, suffering and care and the organizational culture
      of Finnish maternity care. Postpartum care is seldom either technological or
      dramatic and has been shown to take low priority in both practice and research.
      This article uses the theoretical perspective of Eriksson as a basis for
      discussing insights gained from the phenomenological study. Nine women were
      interviewed at the end of their pregnancy, and 3 weeks, 3 months and 21/2 years
      after giving birth. The research approach was that of Colaizzi, which has its
      roots in phenomenological philosophy, and which attempts to present accurately
      the lived experiences of those studied. Data suggest that the transitional
      process from being an expectant mother to being a new mother occurs slowly but
      intensely in a unique way during the first days after the baby is born. The new
      mother experiences caring communion in sharing her life situation with the
      midwife, learning directly through the midwife's teaching and indirectly when the
      midwife enables her to be in peace and quiet together with her baby and family.
      Other new mothers are caring towards the woman reciprocally, sharing the same
      situation, helping one another and learning together. Three challenges in
      postpartum care emerge from this study. These are to understand the meaning of
      caring, to involve family and other new mothers more consciously, and to see the
      woman as a new mother who needs both to care and be cared for both by her family
      and friends and by professional carers.

PMID- 9582768
TI  - Evaluation of information given to rheumatology patients using non-steroidal anti
      inflammatory drugs.
AB  - This paper reports the findings of a study of information given to rheumatology
      patients using non-steroidal anti-inflammatory drugs. One hundred and twenty
      patients were randomized to three groups. Group A received an information
      leaflet, Group B received both a leaflet and a verbal explanation and Group C
      received only a verbal explanation. Information was gathered on demography,
      knowledge base, sources of information, satisfaction with the leaflet and further
      information requirements. Data were collected by questionnaires which were
      completed before randomization and 8-12 weeks later. Analysis indicates the
      potential benefits of giving information to patients although the full
      implications of these benefits are not clear and further research is indicated in
      this important area.

PMID- 9582769
TI  - AIDS in Norway: a post hoc evaluation of an AIDS home care project.
AB  - Norway's National Health Care system guarantees all citizens a right to health
      care within a decentralized system based on values like solidarity and equality.
      Seventy-five per cent of people with HIV/AIDS live and are treated in Oslo, the
      capital. Local home care agencies have minimal, if any experience working with
      AIDS patients residing in the community. Therefore a home care team with two
      nurses employed by the hospital was established as a 2-year trial project to
      establish a home care system for AIDS patients. In March 1993 a post hoc
      evaluation of the project for AIDS patients was completed, based on descriptive
      data. Results seem to indicate that a prerequisite for patients to live at home
      is someone to do chores like cleaning, laundry and shopping. The home care nurses
      functioned as vital links between the hospital, the outpatient clinic and the
      local home agency.

PMID- 9582770
TI  - Charting the course of change.
AB  - Change and transition are different concepts. Transition for practitioners in the
      workplace is complex. Transition within roles needs a positive tripartite
      arrangement with teacher and clinical manager. This paper looks at the findings
      from a study of 100 enrolled nurses undertaking a part-time conversion programme
      to RGN, RMN or RSCN. Evidence suggests that student perceptions change over time
      within a 2-year programme. This conversion programme is seen as a positive
      experience by participants and employers.

PMID- 9582771
TI  - Acute confusional states after admission to hospital.

PMID- 9582772
TI  - From outside the walls: a qualitative study of nurses who recently changed from
      hospital-based practice to home health care nursing.
AB  - Acute care facilities are no longer viewed as the center of the health care
      network. Efforts to reduce hospital length of stay will continue to spur the
      growth of care delivered in homes. With the downsizing of many hospitals, the
      need for nurses in acute care settings will decline. Many acute care nurses are
      finding themselves seeking employment opportunities in home health care settings.
      The purpose of this study was to examine nurses' experiences when they change
      from hospital-based practice to home health care nursing. The qualitative mode of
      inquiry was used to conduct taped-recorded interviews of 25 baccalaureate
      prepared nurses in a large metropolitan area. Stressors experienced by the nurses
      were identified as well as adaptations required to minimize role stress.
      Continuing education programs can provide information and skills needed to
      improve nurses' competencies to function in a health care system projected to be
      more community-based, which includes home health care.

PMID- 9582773
TI  - A gaming strategy for teaching the use of critical cardiovascular drugs.
AB  - This article reports the use of a successful strategy for teaching non-critical
      care nurses how to safely administer critical cardiovascular drugs. The use of a
      gaming technique to accomplish this, accompanied by a caricature case study, is
      described in detail. Participants' evaluations evidenced a high degree of
      satisfaction and enjoyment in learning the pharmacological content. Readers can
      adapt this game to other learning topics for rapid and effective learning of
      material specific to their institutions.

PMID- 9582774
TI  - A descriptive study of continuing nursing education programs in academic
      settings.
AB  - This article describes survey results from 24 collegiate continuing nursing
      education programs in the United States. The purpose was to collect baseline data
      regarding the role of the continuing education (CE) administrator, the
      characteristics of financial information, and the organizational structure of the
      department. The findings showed that roles and responsibilities of the directors
      in continuing nursing education include both administrative activities and
      faculty responsibilities. The trend toward decreasing enrollments of CE
      registrants will make it imperative for the CE administrator to explore creative
      programming directions, configure an affordable staffing arrangement within the
      organization, and generate new sources of program revenue.

PMID- 9582775
TI  - The dilemmas of experiential teaching: toward an interpretive approach.
AB  - Continuing education in nursing uses the experience of the learner as a basis for
      the examination of practice issues. The unique and personal nature of this
      experimental learning is, however, particularly problematic where assessment of
      the learner or the course is required. This article offers part of the findings
      from an evaluative, ethnomethodological study into the reflections of learners
      attending an experiential course in communication in palliative care. In the part
      of the study described here, the critical perceptions of three learners following
      one experiential exercise are compared with the stated aims of the facilitators
      and their subsequent actions. The analysis uses the conceptual framework of
      Schon's reflection-in-action. It is suggested that an interpretive approach
      toward teaching in the experiential domain may lead to a more relevant assessment
      of learning.

PMID- 9582776
TI  - A comparative evaluation of two educational strategies to promote publication by
      nurses.
AB  - BACKGROUND: Two group educational strategies to promote publication by nurses at
      The Johns Hopkins Hospital were evaluated and found to result in similar success
      rates. METHOD: Eighteen nurses, divided into two groups, attended three monthly
      sessions for instruction, guidance, and encouragement on writing and publishing.
      One group received additional guidance and encouragement during quarterly
      meetings for 1 year. Data were collected on participants' characteristics and
      publication success rates. RESULTS: Both groups achieved similar publication
      success rates. CONCLUSION: A group education program to promote publication by
      novice nurse authors achieved positive outcomes and used resources more cost
      effectively than the traditional method of individual instruction and guidance.
      Two factors having positive effects on publication success were: a) having a
      clear topic for publication at the outset of the educational program, and b)
      holding a positive perception of the value placed on publication within one's
      practice environment. The authors suggest alternative educational and other
      strategies to encourage nurses to share their clinical knowledge through
      publication.

PMID- 9582777
TI  - Evaluation of an HIV/AIDS continuing education program.
AB  - An HIV/AIDS education model was implemented for rural nurses as a demonstration
      project in Georgia. The overall goal of the project was to increase the quality
      of and access to HIV/AIDS-specific services in rural communities. Public health
      and community nurses were the focus of this effort due to their current roles in
      providing health care to rural and underserved populations and their potential
      for networking across health care and social services agencies to form an
      HIV/AIDS response network. One hundred and seventy-five nurses completed the
      program. Program evaluations revealed that, after completing the HIV/AIDS course,
      participants' professional preparedness, attitudes toward people with HIV/AIDS,
      and knowledge had improved. Consistently, participants' scores in each of these
      areas increased from the pretest to the posttest. Additionally, nurses
      participating in the program reported in a follow-up survey that they felt better
      prepared to care for people with HIV/AIDS. While there is a need for further
      HIV/AIDS education in rural communities, results of the program support its
      potential use as a model for other rural communities.

PMID- 9582778
TI  - Leading the team.

PMID- 9582779
TI  - Developing nurse practitioners to develop practice: the experiences of nurses
      working on a nursing development unit.
AB  - AIM: To elicit nurses' accounts of their involvement with nursing research and
      their interpretations of the meaning of these projects for their practice.
      BACKGROUND: The links between research and practice development in health care
      are poorly understood and require further exploration in the light of the
      emerging research and development agenda within the National Health Service.
      METHODS: Semi-structured interviews were conducted with 15 qualified nurses
      working on a Nursing Development Unit. The interviews were tape recorded,
      transcribed and analysed thematically. FINDINGS: Data analysis identified two
      distinct groups--a core group of nurses actively engaged in the research projects
      and a peripheral group involved in data collection. The characteristics of the
      core group mirror the characteristics of those involved in nonresearch-based
      practice development activities. CONCLUSIONS: Engaging in research activities
      does not always result in the development of practice, however, there appears to
      be a link between practice development and critical thinking.

PMID- 9582780
TI  - Taranaki community partnership model.
AB  - BACKGROUND: This exercise was undertaken as part of a re-engineering of community
      health services. 'Community' needed to be defined in order to understand its
      components, to develop a philosophy and a common understanding to assist in the
      re-engineering process. AIM: To define community health as it is understood by
      practitioners in the Taranaki province. METHOD: Workshops were held involving as
      many community workers as possible. Newsletters kept staff informed of
      developments. Individual interviews and phone calls also featured. FINDINGS: A
      community partnership model was developed encompassing the concepts of equity,
      communication, responsiveness and sustainability. The people working within the
      model were staff, client and customer. CONCLUSION: This was a worthwhile exercise
      that resulted in a unique model developed by practitioners for practitioners
      which gave a feeling of 'belonging' to a fragmented service. It has uses in
      further research, in education and in the day to day running of community
      services.

PMID- 9582781
TI  - Co-production--an approach to cardiac rehabilitation from a service management
      perspective.
AB  - AIM: The aim of the study was to describe and analyse the hospital delivery
      system for patients recovering from myocardial infarction, applying the offering
      and value concepts from service management theory. BACKGROUND: In Nordic hospital
      care patients traditionally played a minor role. But changes have taken place. By
      means of information giving and systematic education from the staff many
      chronically ill patients are now taking a significant part in their treatment and
      care. METHOD: The method was a case study including 12 individual interviews.
      CONCLUSIONS: The principal conclusion is that the short and intense periods of
      hospital inpatient stay make it advantageous to consider the patient a member of
      the health care team taking an active part in the caring process.

PMID- 9582782
TI  - Issues for the development of care pathways in mental health services.
AB  - AIMS: This paper seeks to discuss some of the issues for the development of care
      pathways for inpatients with schizophrenia. BACKGROUND: Managed care pathways are
      becoming increasingly popular for general adult conditions. Little is known about
      the development or application of care pathways for mental health services, and
      in particular, for inpatients diagnosed with schizophrenia. METHODS: Action
      research principles were adopted to engage and develop support to examine care
      pathways. Participant observation and unstructured interviews were the primary
      methods used during this phase of the research. The paper draws on the
      experiences of one of the authors (AJ) and his attempt to discuss the potential
      development of a care pathway for in-patients with schizophrenia in one inner
      city locality in London. FINDINGS: Four central issues were identified by the
      group; individualized care versus standardized care, generic practice and generic
      education. CONCLUSIONS: The development and application of care pathways for
      mental health services requires the consent and commitment from the work force.
      Many crucial barriers to development arose during the discussion groups and these
      will require further attention by prospective organizations wishing to apply care
      pathways to complex diagnostic groups such as schizophrenia.

PMID- 9582783
TI  - Occupational stress and job satisfaction: a comparative study of health visitors,
      district nurses and community psychiatric nurses.
AB  - AIM: This study examines self-reported stress and job satisfaction of health
      visitors (n = 68), district nurses (n = 56) and community psychiatric nurses (n =
      19) in one health authority in the UK. The levels and sources of stress and
      satisfaction were examined in relation to speciality. METHOD: Stress levels were
      assessed using The General Health Questionnaire-12. Sources of stress and
      satisfaction were measured by a 47 item questionnaire compiled by the author. The
      analysis of data included analysis of variance, Pearson product moment
      correlation, factor analysis. FINDINGS: The results showed that levels of stress
      were a function of occupation with significant variation between groups. Health
      visitors yielded the highest stress scores and lowest job satisfaction scores.
      Sources of stress correlated significantly and positively with GHQ scores. Factor
      analysis identified four main factors concerned with sources of stress: emotional
      involvement, unpredictable events at work, change and instability at work, work
      content. Job satisfaction scores correlated significantly and negatively with GHQ
      scores; indications were that all three groups were dissatisfied with supervisory
      relationships. CONCLUSIONS: Recommendations include more creative and supportive
      supervisory relationships, such as clinical supervision.

PMID- 9582784
TI  - Nursing students' experiences of the effects of continual process-oriented group
      supervision.
AB  - AIM: To describe and analyse the nursing students' experiences of the effects of
      process-orientated group supervision. BACKGROUND: There is a need to promote the
      development of the nursing student's professional identity and preparedness to
      act as well as to provide the opportunity for reflection and setting up a group
      supervision programme. METHOD: This paper is an in-depth study using both
      quantitative and qualitative methodologies. An open-ended interview form
      including 24 items and four open-ended questions was used and 80 nursing students
      answered a questionnaire. The data were analysed by a factor analysis with
      varimax rotation and by open coding. FINDINGS: The three analysis factors were
      labelled: 'Increased patient attentiveness', Increased empathy ability', and
      'Increased insight and security'. From the findings of the qualitative analysis
      two main categories emerged: 'Increased ability to communicate' and 'Personal
      growth'. CONCLUSIONS: The findings of this study suggest that there is an
      association between the effects of group supervision and the nursing students'
      development of a nurse identity.

PMID- 9582785
TI  - Time-saving tips for preparing your manuscript: strategies for acceptance on the
      first attempt!
AB  - This experienced nurse author and reviewer describes ways to avoid the 10 time
      wasters in developing a manuscript. Many of these strategies can help lead to
      acceptance of the manuscript on the first submission, thus saving revision time.

PMID- 9582786
TI  - Selecting keywords: helping others find your article.
AB  - Keywords or indexing words help the intended audience of your article both
      directly and indirectly. Directly, they help the reader identify the topics
      covered. Indirectly, they help indexers identify the subject headings used in
      journal indexes and databases. This article reviews the indexing process,
      provides a step-by-step way of identifying keywords for your article, and
      identifies some common pitfalls to avoid.

PMID- 9582788
TI  - As a registered nurse in a teaching hospital in rural New Hampshire.

PMID- 9582789
TI  - Changes in nursing education: implications for faculty stress.

PMID- 9582790
TI  - Computer conferencing for graduate students.

PMID- 9582791
TI  - Evaluating online literature searches.

PMID- 9582792
TI  - Learning style and preferred technology: videotape vs. interactive videodisc.

PMID- 9582793
TI  - Practice placements: we have the ingredients but do we have a recipe?

PMID- 9582794
TI  - Problem-based learning.

PMID- 9582795
TI  - Using the Internet to integrate cultural diversity and global awareness.
AB  - Societal paradigm shifts are fundamentally changing nursing education and
      practice. A global view is fostered in business, education, and healthcare; a
      microcosmic view is no longer acceptable. Seeking to increase the global and
      technological knowledge of their students, the authors describe how they used
      electronic technology to integrate cultural diversity and global awareness
      concepts into a nursing curriculum.

PMID- 9582796
TI  - The integrated health professions education program seminar.
AB  - Powerful dynamics of change require practitioners from all disciplines to be
      prepared to work in interdisciplinary teams, competently access health and
      information technologies, and understand the multiple functions required for
      adequate healthcare provision. The University of Iowa's Integrated Health
      Professions Program is a state-funded effort designed to provide students with a
      common educational experience to enable them to work collaboratively in
      underserved or rural settings. Students take part in a series of team-building
      seminars including technology-based instruction and activities in conjunction
      with visits to community clinical sites. The authors discuss the experiential,
      collaborative, and cooperative forms of learning that take place during the
      seminar series.

PMID- 9582797
TI  - Disabled nursing students in the classroom.

PMID- 9582798
TI  - Academic advising from a nursing theory perspective.
AB  - Academic advising is an important faculty role; it not only assists students in
      selecting appropriate courses, but it also helps them make choices about personal
      and career goals. Using a theoretical framework to guide the advising process can
      make advising sessions more efficient and effective. One nursing theory, modeling
      and role-modeling, is presented here as a framework for student advising.
      Modeling and role-modeling theory can guide the advisor to establish a caring
      interpersonal relationship with the student and plan individualized strategies to
      meet educational goals.

PMID- 9582799
TI  - Meeting the learning needs of diverse students in BSN programs.

PMID- 9582800
TI  - Research utilization by undergraduate students.
AB  - In our experience as nurse educators, baccalaureate students, after completing an
      introductory research course, are not prepared to critique research studies
      skillfully and determine their potential use in professional practice. Also,
      staff nurses need help determining the appropriateness of implementing research
      findings into clinical practice. To remedy this situation, a research utilization
      component was successfully incorporated into a senior-level clinical course. This
      approach has implications for improving patient outcomes.

PMID- 9582801
TI  - A computer simulation for teaching critical thinking skills.
AB  - Critical thinking is difficult to teach because it is an abstract conceptual
      skill and there is no standard model. The authors discuss the development and use
      of a computer simulation that stimulates critical thinking in nursing students.
      Computer simulations are an efficient method of teaching students content and
      critical thinking skills without exhausting severely limited clinical time or
      placing a patient in jeopardy.

PMID- 9582802
TI  - Service-learning for graduate students.
AB  - Although service-learning is gaining momentum in academic settings across the
      country, it has not been described as a feature of graduate education. This
      project incorporated a ten-hour service requirement into a unit on theories of
      nurse caring as part of a course for graduate nursing students, Theories and
      Concepts of Nursing. The authors describe the service-learning experience, as
      well as the extensive class reflection process and written synthesis with caring
      theory and the University mission after completion of the service.

PMID- 9582803
TI  - Educating the culturally diverse healthcare student.
AB  - Diversity among healthcare students is increasing as the population of the United
      States changes in composition. Preparation of the culturally diverse healthcare
      student presents a challenge for recruitment, education, and retention. The
      problems of education can be ameliorated by a thorough assessment of the
      culturally diverse student using the Giger and Davidhizar model. The student
      should be assessed for differences by considering six interrelated factors:
      communication, space, time, social organization, environmental control, and
      biological variations. Understanding the differences that exist in these areas is
      a first step toward appreciating the diversity among people of varied cultures.

PMID- 9582804
TI  - Enhancing the language development of immigrant ESL nursing students: a case
      study with recommendations for action.
AB  - Immigrant nursing students who use English as a Second Language (ESL) are
      becoming a significant population in nursing education classrooms today.
      Frequently, nurse educators feel at a loss as they struggle to help students
      achieve their educational goals. The authors offer an analysis of one of the
      problems nurse educators and immigrant ESL nursing students face: language
      development. A case study that has as its theme the problem of language
      development is presented. Relevant second language acquisition research findings
      are outlined and appropriate teaching practices are suggested. This research and
      these practices are used to identify actions that nurse educators and their
      students can take to enhance and improve the language development of immigrant
      ESL nursing students.

PMID- 9582805
TI  - Teaching caring within the context of health.
AB  - Changes in the delivery of healthcare have created an environment viewed as
      uncaring to both the patient and healthcare providers. Thus teaching concepts of
      health and caring becomes a priority for nurse educators. The authors discuss how
      caring can be taught in the context of health. Specifically, they describe a
      teaching method which was aimed at sensitizing students to Allen's model of
      health and Watson's carative factors.

PMID- 9582806
TI  - Nurse case managers bring the element of caring to cost-contained care.

PMID- 9582807
TI  - How do you think case management has benefited patients?

PMID- 9582808
TI  - Should congress legislate health care because health plans and providers cannot?

PMID- 9582809
TI  - Vice President Gore announces historic initiative in the battle against cancer.

PMID- 9582810
TI  - [... to live in a most possibly normal environment...].

PMID- 9582811
TI  - ["Adoptive daughter or daughter in law wanted for the maintenance of the
      generational contract"].

PMID- 9582812
TI  - ["Caring with people": an initiative of the Vorarlberg government and the
      Batschuns School with the support of Radio Vorarlberg and the Vorarlberg News].

PMID- 9582813
TI  - [Working with family as a part of the analysis of an existing condition].

PMID- 9582816
TI  - Advanced practice role of the outcomes manager.

PMID- 9582814
TI  - Accountability: the Phoenix rises.

PMID- 9582815
TI  - Structure and process constraints on nursing accountability.

PMID- 9582817
TI  - Questions to ask: implementing a system for clinical pathway variance analysis.
AB  - Although it is agreed that there is a need for clinical pathway variance
      analysis, methods for creating a system are less well defined. To help others
      down this path, we have developed a list of questions around four core issues:
      data collection, data entry and analysis, data reporting, and organizational
      support. Our goal is to identify key questions related to variance management and
      provide a framework for clinical pathway variance analysis.

PMID- 9582818
TI  - Heart failure collaborative care: an integrated partnership to manage quality and
      outcomes.
AB  - Heart failure is a prevalent chronic condition with increasingly high rates of
      mortality and morbidity, frequent exacerbations, and multiple hospitalizations.
      The financial impact of this disease is staggering, with more than $10 billion
      spent annually. This article describes a heart failure service that provides five
      essential components of integrated care management for heart failure patients
      across the continuum. The program may serve as a model to others in developing
      programs to meet the unique needs of heart failure patients and patients with
      chronic diseases.

PMID- 9582819
TI  - Maternity care outcomes: assessing a nursing model of care for low-risk
      pregnancy.
AB  - This study compared two models of maternity care for low-risk pregnant women. It
      was found that freestanding birth centers offer high-quality, cost-effective
      maternity care. The results of this study strongly support the need to find ways
      to educate managed care organizations, employers, and the public about both the
      quality of these services and economic value. This research method may be useful
      in assessing other emerging models of care.

PMID- 9582820
TI  - Potential use of small area variations analysis in nursing outcomes research.
AB  - Small area variations analysis (SAVA) is a method for measuring and analyzing
      differences in clinical practice and service utilization across small geographic
      areas. To date, nursing has not adopted a SAVA approach in patient outcomes
      studies. A discussion is offered of the conceptual and methodological
      considerations confronting researchers and outcomes managers who wish to conduct
      a small area variations analysis followed by examples and suggestions for
      incorporating SAVA into nursing practice.

PMID- 9582821
TI  - Standardized nomenclatures: keys to continuity of care, nursing accountability
      and nursing effectiveness.
AB  - Standardized nursing nomenclatures must be included in clinical documentation
      systems to generate data that more accurately represent nursing practice than
      outcomes-related measures currently used to support important policy decisions.
      NANDA, NIC, and NOC--comprehensive nomenclatures for the needed variables of
      nursing diagnoses, interventions, and outcomes--are described. Added benefits of
      using NANDA, NIC, and NOC in everyday practice are outlined, including
      facilitation of the continuity of care of patients in integrated health systems.

PMID- 9582822
TI  - Core competencies for outcomes management in nursing.
AB  - Nurses have frequently assumed responsibility for the examination of outcomes
      within the health care system. As nurse case manager, outcomes manager, or care
      manager, these roles signify both a different way of doing business and a new set
      of expectations and competencies. The educational preparation for these roles
      varies dramatically. As outcomes measurement and management have become a
      critical arena for nursing leadership, a graduate-level course, Health Care
      Outcomes Measurement, was developed. Core competencies for outcomes measurement
      and management are presented in this one course, rather than as individual topics
      in established courses. In this manner, graduate students are exposed to the
      interdependent nature of care management and outcomes measurement while becoming
      knowledgeable consumers of outcome data. This article describes the need for
      course development and presents the objectives, content, and assignments for this
      course.

PMID- 9582823
TI  - The role of government.

PMID- 9582824
TI  - Occupational health & safety. Bullying.

PMID- 9582825
TI  - Whoops ... there goes the social wage.

PMID- 9582826
TI  - Aged care funding--back to the future.

PMID- 9582827
TI  - What you should know about Queensland workplace agreements.

PMID- 9582828
TI  - Clients without decision-making capacity and you.

PMID- 9582829
TI  - Nurse in profile.

PMID- 9582831
TI  - [Quality of life from the viewpoint of patients with spinal cord lesions].
AB  - Before the existence is negotiating of individuals that present lesion medular,
      we came across the problem involved in the daily of those people after a
      situation of sudden and unexpected trauma. With the intention of rendering
      effective cares to these people worried, in this study, in identifying the
      situation for the which they are passing, there were been changes and which were
      them, so much in psychic level as physicist and social. For so much, he/she/it
      opted for the accomplishment of a semi-structured individual interview, being
      used the resource of the recording, the instrument of collection of data consists
      of identification data and data regarding the interviewee's life. The speech free
      with recording and posterior transcription characterizes a study of case of
      nature, above all, exploratory. The obtained data received a thematic analysis
      using conceptions about life quality according to FORATTINI (1991). In this study
      they were identified a physical deficiency and a series of inabilities. The
      deambulacao is the first loss noticed by the patient after the lesion and its
      first subject to the professional closer of him, it is that settles down a
      communication channel that allows this expression. But we should remember the
      possible process of rehabilitation that doesn't approach only the search for the
      locomocao, permeating the re-learning in this new life situation. We verified
      modifications in all the spheres (physics, social, psychological), and the most
      affected. according to the picked data, went the psychological and to social due
      to the physical alterations. The main loss sensation refers to the social paper,
      and this is characterized, mainly, for the impossibility of coming back to the
      work. The changes in the solemnity-image conceptions and self-esteem were also
      identified, in smaller degree, for the sensation of inability. The more important
      and comprehensibly told physical loss refers the sensibility loss and motive
      capacity of the members.

PMID- 9582830
TI  - Choosing the right adviser.

PMID- 9582832
TI  - [Postural problems and problems of equipment: an ergonomic study of users of
      microcomputers in a nursing school].
AB  - The computer usage has become essential nowadays and the Nursing staff meeting
      this technological improvement has been assimilating it in practice, which is
      started in Graduation course. As users of the computer division from a Nursing
      School we have observed students' complaints related to adequacy of the furniture
      used, then, we were interested in developing this research which has as object to
      analyze the furniture from the computer division according to the ergonomic
      recommendations and identify body posture adopted by the students in typing
      activity. The procedures used were performed in three stages, which were: free
      supervision of environment and furniture measure, surveillance of body posture
      and interviews. The results pointed out that the furniture is inappropriate
      referring to: fixed counter without foot support, without document case; chairs
      are not regulative, back support width out of recommended standards, there are no
      armrest and wheels, there are only four legs and the covering is slimy and stiff.
      Only in 18.6% of the observation period the students adopted to perfect posture
      in typing activity, that is, upright spinal column, elbows at the same level of
      the counter, deflected legs and supported feet. It is suggested that the
      workplace be planned for typing from known facts related to anthropometric
      dimension of the users and use of proper furniture in order to obtain a
      concordant set among furniture, milieu and user providing comfort and avoiding
      health problems.

PMID- 9582833
TI  - [Evolution of the demand for the undergraduate nursing course at the Federal
      University of San Carlos].
AB  - This study analyzes the evolution of demand for the nursing undergraduate course
      of Federal University of Sao Carlos (UFSCar), from the first entrance examination
      in 1977 to 1996. The economic crises and the crises in health social programs
      affected significantly the demand for this entrance examination which declined
      abruptly 1980. During 1990, the demand for this nursing program was two
      candidates per chair, the lowest level since its foundation in 1977. From 1991,
      the recovery of the Brazilian economy associated with a change in the health care
      system were responsible for the increasing in the demand of nursing
      professionals. In 1990 the entrance examination started to be done by another
      institution (FUVEST, one state foundation responsible for this examination). The
      FUVEST was already responsible for the entrance examination for two others sao
      Paulo State Universities. Starting in 1990 the candidates could compete
      simultaneously for the nursing program at the three universities through the same
      entrance examination. The UFSCar always was the last option for the candidates
      among those universities. However, the candidate demand for that program at
      UFSCar, as the first option, increased to six candidates per chair in 1995 with a
      small decrease in 1996 (4, 6 candidates/chair). During 1982 and 1986,
      respectively three and six chairs, out of 30 offered by UFSCar, were not taken,
      this number increased to 15 during 1990. This great decrease in the interest for
      this nursing program, during 1990 could be attributed to three factors: First,
      the decrease in the candidate numbers that applied for this examination (around
      2/1). Second, the degree of difficulty of the examination requirement. Third, the
      bureaucratic procedures that the candidates had to fulfill, after being approved,
      to get enrolled in the program.

PMID- 9582834
TI  - [Phenomenology and nursing: reflections].
AB  - The project is about phenomenology and its elements. It points out the essential
      ideas of existential phenomenology interpreted by Maurice Merleau-Ponty's ideas
      and tries to connect this philosophy to nursing world.

PMID- 9582835
TI  - [Ethnographic studies in nursing].
AB  - This article makes an deals with ethnographic research in nursing. It discusses
      the goal and the relevance of this kind of research the professional context. It
      includes also issues related to rigor and ethics. It points out basic aspects of
      participant-observation and ethnographic interview methods, and makes an overview
      of data collection, analysis and utilization of this data for culture
      description.

PMID- 9582837
TI  - [Nursing--construction of a model based on the medical discourse].
AB  - The purpose is to trace a parallel between the medical discourse contents and the
      expected and stereotyped nurses behavior at the beginning of the twentieth
      century. It is a historic-social approach in which was made use of speeches
      uttered by nurses and physicians at nursing and medicine schools. The analysis of
      physicians discourse compared to nurses discourse disclose the formation of a
      mentality shaped and turned docile by the medical power which wanted them holy
      and servile.

PMID- 9582836
TI  - [Multiprofessional relationship with children and family: a challenge for the
      staff].
AB  - This work focus the importance of the relationship existent between the
      multiprofessional staff, the hospitalized child and the responsible. The authors
      identify and comment about the positive and negative points of the pediatric
      units studied, as well as the orientations given by the staff and assimilated by
      the children and responsibles. Multiprofessional relationship X child X
      responsible: challenge to the staff.

PMID- 9582838
TI  - [Historical and organizational aspects of medical air transportation: dynamics of
      nursing assistance].
AB  - The assistance dynamics of nursing was based in the stages analysis which guide
      the nurse's performance and comprise the organizational structure of the Service,
      fluxogram request, aircraft physical design, and assistance dynamics. The
      utilization of nursing care systematization with the use of the proposal of a
      nursing report to be adapted during the patient's transport.

PMID- 9582839
TI  - [Profile of nursing research on intensive care in Brazil].
AB  - This is an analysis about critical care research production and publication as
      well as nursing research's profile in Brazil, focusing on the research producer,
      the research product and the product consumer.

PMID- 9582840
TI  - [Social representations in nursing: commentaries on theses and dissertations].
AB  - The starting point of this work consists on a revision of thesis and
      dissertations developed by nurses aiming to check how the social representation
      was used as a theoretical referential on these researches. Through a systematic
      reading of these works some points were dettached, as thematic, main result as
      and reflections proposed in order to atain professional practice nursing. It was
      ascertained from the analysed work that this theoretical referential is used by
      nurses, and that some studies developed introduce significative results from
      these professionals.

PMID- 9582841
TI  - [Transcultural nursing and beliefs: values and practices of the Gypsy
      population].
AB  - It's a question of mini-ethnographic study in nursing where it is emphasized the
      belief of cares, mettles, way of life, world sight of a group of gypsies of
      origin ROM. It was exploited the theoretical referential by LEININGER for helping
      the understanding of this culture, visualizing proposals in procedures and
      decisions of care, so as to provide cares culturally congruent. The author
      advocates some definitions referring to the especialty of gypsy culture
      concerning its cultural approaches when providing care, as subsidized for future
      studies.

PMID- 9582842
TI  - [Peripheral specimen collecting centers. Preanalytical control].
AB  - The progressive decentralization in the process of sample drawing and collection
      of biological samples has produced a socio-economical improvement for the general
      public and for health systems specifically even though this requires a higher
      degree of control to avoid pre-analytical errors derived from this procedure by
      the laboratories receiving these aforementioned samples. This study is based on
      372,243 drawings, taken from June 1994 until December 1996 at 74 sample drawing
      centers and the systematic recording of any errors committed during the drawing,
      conservation and transportation of the diverse biological samples drawn. The
      results indicate an overall incident rate of 1.5% broken down by year as 1.3% in
      1994, 1.3% in 1995 and 1.9% in 1996 and broken down by type as 0.7% in blood
      samples, 0.7% in urine samples, and 0.07% due to other errors such as
      transportation. DISCUSSION AND CONCLUSIONS: 1. The incident rate is slightly
      lower than that obtained in a prior study of similar characteristics. 2. The
      small increase in the incident rate which occurred in 1996 is attributed to an
      improvement in the error recording system. 3. We recommend continuing applying
      strategies which permit one to detect, limit, and if possible, reduce these types
      of errors. These strategies include periodical meetings and professional
      development.

PMID- 9582843
TI  - [Nursing records for discharge. Report of the nursing history].
AB  - The quality of care within our health care system depends upon an active and
      dynamic communication which bridges the different levels of care (primary and
      hospital) and will permit a continuity of services between the distinct parts. To
      insure this success, the authors propose an outpatient nursing record that will
      follow the patient upon his or her discharge. This record, to be called the
      "Discharged Patient Report", will be directed to other medical professionals so
      that they can be informed of previous treatments that the patient has received.
      Included in the report will be items such as; the previous nursing interactions
      that were used on the patient, how problems were resolved, possible other
      solutions, and health care information given to the patient. Using the report in
      this way will give us a great tool to know our patients and better understand how
      to serve them.

PMID- 9582844
TI  - [Management of cases and planning of care].
AB  - This article describes the process followed to integrate the design of
      standardized treatment plans in mental health with the management of cases
      methodology. In addition, this article describes the procedure to follow in order
      to achieve the objectives programmed as a basis for future research in nursing.

PMID- 9582846
TI  - [Treatment plan. # 2. Unit of medium and long-term care].

PMID- 9582845
TI  - [Care plan # 1. Mental health center].

PMID- 9582847
TI  - [Treatment plan # 3. Emergency/acute care unit].

PMID- 9582848
TI  - [Nuclear medicine and nursing].

PMID- 9582850
TI  - [Plantar arteries: deep aspect].

PMID- 9582851
TI  - [Pediatric radiography. The nurses' role].
AB  - After a brief review of advanced radiographic diagnostic techniques, how to
      utilize them in the most cost-effective manner and minimize their risks, the
      authors examine the role of the nurse in using exploratory radiography in
      children. Patient opposition, immobilization and protection are some of the
      possible problems that one might encounter when working in this setting.

PMID- 9582849
TI  - [Juvenile onset diabetes: the effect of education for metabolic control].
AB  - This study analyzes the repercusions that education about diabetes and frequent
      periodical checkups or intensive followups have on the metabolic control of this
      disease. A group of 13 young diabetics, ranging in age from 5 to 13.4, were
      submitted to trimestral clinical and analytical controls during a continuous 36
      month period starting at the outset of their illnesses. Each received
      conventional insulin therapy, two daily injections of a mixture of regular
      insulin/NPH. Annual checkups registered 3.8 +/- 0.4. Four patients, or 30.8%, had
      an attack of symptomatic hypoglycemia. None of these required hospitalization for
      ketosis. The HblAc level at the outset of their illnesses was very high, 11.2 +/-
      2.7%, but this dropped to normal levels, 7.1 +/- 1.5%, during the first trimester
      of treatment, and stayed quite normal for the duration of the study except at the
      21-month checkup, 8.7 +/- 1.8%, and at the 33-month checkup, 8.6 +/- 1.4%. As
      soon as metabolic irregularities were detected, all that was necessary so that
      the succeeding checkups improved notably was to review the items which the
      patient had neglected such as diet and self-checks. The impact of the initial
      medical report and the educational component of the periodical checkups seem to
      be the keys for the quality of a child's metabolical control over time. To sum
      up, bear in mind that a young diabetic tends to begin to show difficulties in
      his/her metabolic control about 21 months after the outset of his/her disease, in
      spite of an intensive checkup program. To a large degree, a solution will depend
      on the professional competence of the medical team treating the patient, and
      moreover, on the degree of knowledge about diabetes which the patient and/or
      his/her family have received.

PMID- 9582852
TI  - [Urethral catheters].
AB  - After a historical summary on the development of urethral catheters, this article
      analyzes various aspects about catheters. These aspects include: types of
      catheters and their recommended use, their counterindications, their
      classification, how to select the appropriate catheter, the information which a
      patient should be provided regarding the use of a catheter, the techniques and
      equipment necessary for their use, the most common problems encountered and how
      to solve them,...

PMID- 9582853
TI  - [New drugs].

PMID- 9582855
TI  - [Plantar arteries (upper aspect)].

PMID- 9582854
TI  - [Diet and arterial hypertension].
AB  - All evidence collected in studies up to present times leads us to believe that
      arterial hypertension can be caused by two main factors: a genetical factor which
      determines a specific susceptibility to hypertension and environmental factors.
      Included in these environmental factors are the following: excessive consumption
      of salt, insufficient intake of calcium or potassium, an increase in the caloric
      content in one's diet, obesity, consumption of saturated fats and cholesterol, or
      excessive drinking of alcoholic beverages. The objective of this article is to
      present the reader with an up-to-date view of how arterial hypertension can be
      treated with dietary measures.

PMID- 9582856
TI  - [Confidentiality and informed consent. A necessary reflection].
AB  - This article analyzes a patient's rights to confidentiality, to be informed, to
      be able to freely exercise his/her choice, and to opt to not have an
      investigation or experiment carried out on his/her body. This article deals in
      depth with the confidentiality issue in health care, reviewing the roles of the
      patient and the health care professional. Finally, this article presents a
      detailed analysis about informed consent, tracing its legal origins and
      development, the ethical principles which should compose it, the proper way to
      present information about it, etc.

PMID- 9582857
TI  - [Prevention of household accidents].
AB  - A study carried out by the Basic Health Area (ABS) in the neighborhood known as
      Nord Raval in Barcelona focused on the detection of household risk factors on
      patients cared for by this health center. This project received a grant from the
      Health Investigation Fund (FIS) in 1996, file number 96/0820. This project has
      three parts spread out over a three-year period. This first part, which has now
      been finished, consisted of a survey of neighborhood residents over 65 years old
      to determine if accident risk factors exist in their homes. This survey provided
      proof that potential accident risk factors do indeed exist in neighborhood homes
      and furthermore, many of these may have a simple solution such as removing rugs
      or other objects which obstruct passageways or moving heaters a few centimeters
      back from inflammable materials. Housecalls by nurses are a fundamental element
      in reducing these accident risk factors.

PMID- 9582858
TI  - [Breast feeding. Health related and sociocultural influences and challenges].
AB  - Breastfeeding is being abandoned as the preferred feeding method in the early
      months of baby's life, and many early failures take place among the few mothers
      who attempt to breastfeed their babies. For that reason, sanitation professionals
      must encourage breastfeeding and convince mothers to keep it up, at least, for 4
      6 months after giving birth. Analysis of pregnancy, delivery and after delivery
      sociocultural and sanitary conditions may help sanitation workers to elaborate an
      educational strategy that considers breastfeeding as healthy behavior that should
      he encouraged. The support of sanitation professionals is considered fundamental
      for breastfeeding maintenance, and a more profound training of these
      professionals about every aspect of breastfeeding is necessary. More active
      sanitary policies supporting this healthy behavior should also be established.

PMID- 9582859
TI  - [Pacemaker implantation. The nurse's role].
AB  - This article takes an indepth look at the role of a cardiological nurse in a
      coronary unit of a hospital where this nurse performs an important part in
      treating medical emergencies which seriously affect a patient's life. To begin
      with, a brief introductory section presents the physiological aspects related to
      cardiac stimulation, followed by the possible factors which indicate the use of
      an artificial stimulator. Techniques for implanting various types of pacemakers
      are described. A nurse intervenes in different ways in these procedures: a nurse
      aids in the pre-operation care and technical setup; a nurse aids the doctor while
      the pacemaker is being implanted; and during the postoperation phase, a nurse
      checks on the correct functioning of the pacemaker and if the nurse detects
      complications, she/he strives to bring an early solution to these problems. In
      order to carry out these duties, prior knowledge will provide nurses with a
      sureness of how to act when faced with emergencies.

PMID- 9582860
TI  - [Intravenous therapy. Peripheral catheters].

PMID- 9582861
TI  - [Smoking: bases for intervention].

PMID- 9582862
TI  - [Clinical aspects of smoking. 1. Detection and diagnosis].

PMID- 9582864
TI  - [Clinical aspects of smoking. 3. Results].

PMID- 9582865
TI  - [The program Smoking-Primary care. Intervention against smoking in a health
      center].

PMID- 9582866
TI  - [Memory and behavior disorders in the elderly].

PMID- 9582863
TI  - [Clinical aspects of smoking. 2. Therapy and follow-up].

PMID- 9582867
TI  - [Promoting communication with the elderly patient with dementia].

PMID- 9582868
TI  - [Violence in high schools; myth or reality?].

PMID- 9582869
TI  - [Youngsters, patients, victims of accidents ... and still in school].

PMID- 9582870
TI  - [Acute urinary retention].

PMID- 9582871
TI  - [Hematuria].

PMID- 9582872
TI  - [The urinary tract].

PMID- 9582873
TI  - [Anuria].

PMID- 9582874
TI  - [Renal colic].

PMID- 9582875
TI  - [Acute pyelonephritis].

PMID- 9582877
TI  - [Injuries of the urogenital system].

PMID- 9582876
TI  - [The male genital apparatus: acute infections].

PMID- 9582879
TI  - [The structures of palliative care: assessment, status of facilities,
      perspectives and recommendations].

PMID- 9582878
TI  - [When the days are numbered. Interview by Ghislaine Trabacchi].

PMID- 9582880
TI  - [Mission: hygiene].

PMID- 9582881
TI  - ["They" are telling you ... where you could not go yourself!].

PMID- 9582882
TI  - [Must we reinvent vigilance against infections?].

PMID- 9582883
TI  - Are you ready to meet the challenge?

PMID- 9582884
TI  - Associations Advance America.

PMID- 9582886
TI  - The bottom line.

PMID- 9582887
TI  - Killing providers with criminal prosecution.

PMID- 9582888
TI  - Childhood diabetes and the economic toll on families.

PMID- 9582889
TI  - A faculty perspective on the TNA legislative experience for student nurses.

PMID- 9582891
TI  - Continence nurses: a survey of who they are and what they do.
AB  - This survey is the first report on the characteristics, functions, and barriers
      to practice reported by continence care nurses in the United States. The data
      obtained provide valuable information regarding a new subspecialization in
      nursing.

PMID- 9582892
TI  - Time of day urinary catheters are removed: a study of current practices.
AB  - Nursing abounds with rituals and routines that guide every day clinical practice,
      including nursing practices concerned with the timing of urinary catheter removal
      in adult acute care patients. Many of the underlying assumptions regarding the
      time of day that urinary catheters are removed are questionable and indicate a
      need for further study. An understanding of current practices has the potential
      to contribute to establishing scientific principles on which rational nursing
      care can be based.

PMID- 9582893
TI  - An assessment of a vacuum constriction device in treating erectile dysfunction.
AB  - Male erectile dysfunction is a common health concern, affecting an estimated 15
      million men between the ages of 18 to 59. A vacuum constriction device, a
      mechanical apparatus using vacuum pressure to draw blood into the erectile tissue
      of the penis and a constriction ring worn at the base of the erect penis to
      maintain the erection during intercourse, is a highly efficacious treatment when
      combined with an instructional protocol and systematic followup program.

PMID- 9582894
TI  - Asepsis: back to the basics.
AB  - Nosocomial infections are the 11th leading cause of death in the United States,
      cost approximately $4.65 billion yearly--and can be prevented. Patients are at
      risk for nosocomial infection, especially when they undergo surgical procedures.
      It is important to know and carry out the principles of asepsis to reduce this
      risk of infection regardless of where the procedure occurs.

PMID- 9582896
TI  - Getting ready for advanced practice certification: urolithiasis.

PMID- 9582897
TI  - Nonsteroidal anti-androgens: role in treating advanced prostate cancer.

PMID- 9582898
TI  - Pharmaceuticals. Drug prices rise.

PMID- 9582899
TI  - Ethics. The view from HMOs.

PMID- 9582900
TI  - Management. The farther they fall.

PMID- 9582901
TI  - Public health. AIDS research.

PMID- 9582902
TI  - Focused factories. Are you ready for the competition?
AB  - Dinosaurs--big body, little brain. That's how one entrepreneur sizes up today's
      general hospitals. Some analysts and investors agree. They're betting on "focused
      factories," hospitals that specialize in heart care, orthopedics, and other
      services. But the so-called dinosaurs are fighting back.

PMID- 9582903
TI  - Home-grown health plan.
AB  - Most companies in Sullivan County, N.H., employ fewer than five people, so a
      decade of economic decline meant many could't afford to offer health benefits.
      Valley Regional Healthcare saw its chance to help out the community, launching an
      HMO-style plan that keeps control--and spending--local.

PMID- 9582904
TI  - Out of reach.
AB  - The disabled poor worry whether managed care will bring them into the medical
      mainstream or cast them adrift. That's why state Medicaid programs are
      approaching the task gingerly--if at all.

PMID- 9582905
TI  - Tobacco settlement. Butting heads.

PMID- 9582906
TI  - Antiviolence. Triage for trouble spots.

PMID- 9582907
TI  - Consumers. Power to the patients.

PMID- 9582909
TI  - Medicare. Senior expenses.

PMID- 9582908
TI  - Pharmaceuticals. Patent pain.

PMID- 9582910
TI  - Court rulings. Death or taxes?

PMID- 9582911
TI  - Compliance. Where's the leniency?

PMID- 9582912
TI  - Technology. Year 2000.

PMID- 9582913
TI  - Pharmaceuticals. AZT price cut.

PMID- 9582914
TI  - Human resources. Seeking a balance.

PMID- 9582915
TI  - A dose of dignity. North Dakota program gives free care to low-income kids
      without looking like a handout.

PMID- 9582916
TI  - Blue skies or black eyes? HEDIS puts not-for-profit plans on top.
AB  - For the first time, the Health Plan Employer Data and Information Set, better
      known as HEDIS 3.0, takes the lid off managed care quality and patient
      satisfaction on a national scale. Not-for-profit plans, our analysis shows, have
      the edge on both counts. They also lose the most money.

PMID- 9582917
TI  - Contract balks.
AB  - Fed up with insurers dictating contract terms, doctors are fighting back by
      putting the American Medical Association on the job. Yet the AMA's remedy--a
      bulky "model" agreement--may lack the power of persuasion.

PMID- 9582918
TI  - Tech travails. Computer pros have seen the future--and they're plenty worried
      about how they'll get there.

PMID- 9582919
TI  - Brain drain. A shortage of technical talent is hitting health care especially
      hard.

PMID- 9582920
TI  - CPR training. Finally, system sellers are laying out real-world steps to
      computerized patient records.

PMID- 9582921
TI  - The redistricting of Columbia.
AB  - Thomas Frist worked up a familiar formula for ailing Columbia/HCA, opting to spin
      off one-third of its hospitals. The change promises Columbia and its offspring
      more capital and management scrutiny, but the recovery isn't complete.

PMID- 9582922
TI  - Joint ventures. Money for mission.

PMID- 9582923
TI  - Call centers. A con job.

PMID- 9582924
TI  - Labor unions. Collective threat.

PMID- 9582925
TI  - Palliative care. Parting gestures.

PMID- 9582926
TI  - [The 71st annual meeting of Japan Society for Occupational Health. Morioka City,
      Japan. April 22-24, 1998. Abstracts].

PMID- 9582927
TI  - Novel pneumococcal surface proteins: role in virulence and vaccine potential.

PMID- 9582928
TI  - Thwarting host immune responses in periodontal disease.

PMID- 9582929
TI  - Probiotics, prebiotics or 'conbiotics'?

PMID- 9582930
TI  - Candida albicans hyphal formation and virulence: is there a clearly defined role?

PMID- 9582931
TI  - The immunopathogenesis of tuberculosis: a new working hypothesis.

PMID- 9582932
TI  - Host defense to Pneumocystis carinii: the missing pieces in the jigsaw.

PMID- 9582933
TI  - Gliding into the cell: myosins hold the key to invasion by Toxoplasma gondii.

PMID- 9582934
TI  - On the origin and function of pili.

PMID- 9582935
TI  - Antibody-mediated protection against intracellular pathogens.
AB  - The view that antibody-mediated protection is unimportant against intracellular
      pathogens is not supported by the literature. In fact, there is convincing
      evidence that antibody can protect against many important intracellular
      pathogens. The challenge now is to identify antigens that elicit protective
      antibodies, use them in vaccine design and understand how humoral and cellular
      immune mechanisms cooperate.

PMID- 9582936
TI  - Mechanisms of latency in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis can persist within the human host for years without
      causing disease, in a syndrome known as latent tuberculosis (TB). As one-third of
      the world population has latent TB, placing them at risk for active TB, the
      mechanisms by which M. tuberculosis establishes a latent metabolic state, eludes
      immune surveillance and responds to triggers that stimulate reactivation are a
      high priority for the future control of TB.

PMID- 9582937
TI  - Changing the end: antigenic variation orchestrated at the telomeres of African
      trypanosomes.
AB  - African trypanosomes express the gene encoding their variant surface glycoprotein
      (VSG) surface coat from one of many telomeric expression sites. This genomic
      location at chromosome ends not only allows easy exchange of VSG gene cassettes
      using various mechanisms of DNA recombination but also appears to play a role in
      VSG gene expression site control.

PMID- 9582938
TI  - Emerging targets for the development of novel antifungal therapeutics.
AB  - Invasive mycoses have become important causes of morbidity and mortality in
      immunocompromised patients. New approaches for antifungal therapy are required to
      meet the challenges imposed by these life-threatening infections. Such approaches
      are being developed through identification of novel biochemical and molecular
      targets of pathogenic fungi.

PMID- 9582939
TI  - [Asthma and polyposis].
AB  - For many years, the association between asthma and naso-sinus pathology has been
      noted in the literature. The role of sinus infections on the triggering or
      aggravation of asthma has been well established. More recently attention has been
      drawn to the association of the chronic inflammatory rhino-sinus pathologies such
      as polyposis, with asthmatic illness. Its research and identification are
      essential in care of the asthmatic patient, since recent work has shown the value
      of control of polyposis for the stability and improvement of the asthmatic
      illness. The authors report and analyse the diagnostic and therapeutic methods
      for polyposis in asthmatics.

PMID- 9582940
TI  - [Evaluation of the quality of 2 techniques for measuring IgE: the Pharmacia CAP
      System (Pharmacia & Upjohn Diagnostics) and Alastat (DPC-France)].
AB  - The reliability of results given by specific IgE dosages technology is
      conditioned by the quality of the technology used. Analytical comparison of two
      techniques (Pharmacia CAP System and Alastat-DPC) shows important behaviour
      differences in the evaluation of the precision/reproducibility of results and in
      dilution tests. The Pharmacia CAP System demonstrates qualities comparable to
      those awaited from any immunodiagnostic test. The Alastat techniques shows high
      imprecision and the dilution tests make us wonder about calibration and/or
      ability of the support used to fix all epitopes.

PMID- 9582941
TI  - [Gelatin allergy].
AB  - Allergy to the gelatin used as a plasma filler product has not been recognised
      until now. Methods used have not been validated but are composed of specific
      serum IgE, skin tests and histamine release by leucotrienes. The clinical
      observation that we report has the merit of showing the reality of an allergy
      that is dependent on plasma filler products due to development of a protocol
      which includes firstly, during anaphylactic shock, measurement of the mediators
      of immediate hypersensitivity and secondly, after the clinical accident, test of
      the activation of basophils by flow cytometry (TAB) and measurement of
      leucotrienes.

PMID- 9582942
TI  - Occupational hearing loss in Washington state, 1984-1991: I. Statewide and
      industry-specific incidence.
AB  - This study examined non-federal workers' compensation claims accepted for hearing
      related conditions in Washington state during 1984-1991. Seventy percent of 6,539
      filed claims were accepted (n = 4,547); most accepted claims resulted in
      disability compensation (n = 3,660; 80%). A transient 50-fold increase in claims
      from one worksite accounted for one-third of all hearing-related claims in the
      state for 2 years. The number and incidence of accepted claims from all other
      worksites increased significantly across the study period. The incidence was 0.3
      per 10(3) workers per year, overall, but was at least five-fold higher in
      industries that accounted for half of accepted claims, and reached 38- to 71-fold
      higher in some industries. This study indicates: 1) workers' compensation claims
      under-estimate the true frequency of occupational illness, representing only the
      "tip of the iceberg;" 2) hearing loss is a growing problem in occupational
      health; and 3) workers' compensation data are potentially useful to identify
      specific high-incidence industries for possible interventions.

PMID- 9582943
TI  - Occupational hearing loss in Washington state, 1984-1991: II. Morbidity and
      associated costs.
AB  - This study examined 4,547 workers' compensation claims accepted for hearing
      related conditions in Washington state between 1984 and 1991; 80% resulted in
      disability compensation (n = 3,660). Acute hearing-related conditions comprised
      11% of accepted conditions (95% confidence interval [CI], 2-15%); most claims
      were for chronic noise-related hearing loss. Tinnitus was reported in 64% of
      accepted claims (95% CI, 54-75%). The median binaural-equivalent hearing loss in
      compensated claims was 12.5% (inter-quartile interval, 5-22%; 90th percentile,
      34%), although it declined by 30% during the study period. The number of claims
      and associated impairment increased with claimant age, but the number of claims
      dropped dramatically after age 65. Annual total disability settlements almost
      tripled in 8 years, totaling $22.8 million. This study indicates that
      occupational hearing-related conditions: 1) are manifested by mild to moderate
      hearing loss, accompanied by tinnitus in a majority of cases; 2) may be under
      recognized in older, formerly noise-exposed individuals; and 3) were associated
      with substantial increases in compensation and medical costs over time, through
      1991.

PMID- 9582944
TI  - Occupation and the risk of laryngeal cancer in Uruguay.
AB  - In a case-control analysis involving 112 patients afflicted by laryngeal cancer
      and 509 controls diagnosed with cancers not related to tobacco and alcohol
      exposures, we studied the effects of type of employment and of substances present
      in the workplace on laryngeal cancer risk. Effects were measured relative to
      those never employed or never exposed to the substances. All analyses were
      controlled for age, tobacco smoking, and alcohol drinking through unconditional
      logistic regression and stratified analysis. Among job titles, butchers,
      vintners, bakers, and car assemblers presented elevated risks of laryngeal cancer
      (OR for butchers 2.8, 95% CL 1.1-7.2). Similarly, asbestos, mists from strong
      inorganic acids and pesticide exposures were associated with increased risks of
      laryngeal cancer (OR for strong acids 1.8, 95% 1.1-2.9).

PMID- 9582945
TI  - Prevalence and predictors of long-term work disability due to carpal tunnel
      syndrome.
AB  - The objective of this study was to describe patterns and predictors of work
      absence in the prospective, community-based Maine Carpal Tunnel Study. Three
      hundred fifteen patients with carpal tunnel syndrome (CTS) were recruited from
      physicians' offices throughout Maine. The patients completed questionnaires at
      entry and after 6, 18, and 30 months. The questionnaires included scales
      measuring symptom severity, functional status, general and mental health status,
      exposure to physical stressors, work status, and other indicators. The analyses
      examined univariate and multivariate correlates of work absence. The mean age was
      43, 72% of subjects were female, 71% underwent carpal tunnel release, and 45%
      were receiving Workers' Compensation. Fifty-two percent worked in managerial or
      technical occupations, 15% in service occupations, and 13% in heavy labor or
      machine operation. Forty-five percent of patients changed jobs or were absent
      from work (aside from postoperative recovery) during the 30-month follow-up. In
      multivariate logistic regression models, correlates of work absence at 18 months
      included worse functional status of the hand at study entry and at 6-month follow
      up, involvement of an attorney at the time of enrollment (P < 0.002 for each),
      and work absence at 6 months (P = 0.03). Worse upper extremity functional status
      and having a contested Workers' Compensation claim are critical predictors of
      work absence and should be principal targets of interventions to reduce work
      disability in CTS.

PMID- 9582947
TI  - Use of ultrasonography in monitoring work-related carpal tunnel syndrome: a case
      report.
AB  - Carpal tunnel syndrome (CTS) is a syndrome whose diagnosis is well established.
      One cause could be occupational factors, while others have no relation to work or
      the work environment. We present in this article a case report regarding a worker
      affected by CTS, which is of interest concerning the sensitivity of
      ultrasonography and electroneurography, applied as diagnostic methods, related in
      our protocol to the variations in occupational exposures. The case reports an
      agricultural worker, whose tasks required repetitive and high frequency movements
      of the hand-arm. Diagnosis of CTS used ultrasonography and electroneurography
      techniques. In our opinion, the clinical evolution of CTS encompasses three "work
      related" phases (preclinical phase; phase of nerve compression; phase of
      irreversible damage). Ultrasonography provides greater information about the
      evolution of CTS, as well as other cumulative trauma disorders, and is able to
      discern tendinitis of flexors causing a compression on the median nerve in the
      carpal tunnel.

PMID- 9582946
TI  - Upper extremity nerve involvement in Swedish female machine milkers.
AB  - Entrapment of the median nerve in the proximal forearm, the so-called pronator
      syndrome, is considered a rather rare condition but it is four times more common
      in women than in men. In this study, 23 of 30 female machine milkers with
      symptoms in the forearm and hand were clinically diagnosed as having the pronator
      syndrome. The diagnosis of median nerve involvement was based on the clinical
      history and on physical examination by a hand surgeon. All 23 milkers complained
      of aching in the volar part of the forearm and had a sensation of numbness,
      tingling, and decreased muscle strength in their hands, mostly in the hands which
      usually were statically loaded with heavy equipment. Objectively, all had an
      experience of tenderness over the pronator teres muscle. Furthermore, they showed
      reduced muscle strength, especially in the following muscles: pronator teres
      (PT), flexor carpi radialis (FCR), flexor pollicis longus (FPL), and flexor
      digitorum profundus II (FDP II). To validate the manual muscle testing,
      Mannerfeldt's intrinsicmeter was used to quantify the clinically observed
      weakness. Eight of the 23 milkers with pronator syndrome were surgically released
      from neuropathy and were almost symptom-free at follow-up after six months. One
      patient had a slight sensation of numbness and had to be given surgical carpal
      tunnel release later on. The external exposure of the arm during the application
      of the milking cluster probably causes muscle and fascial tensions that induce
      compression of the nerve. Further studies are needed to establish the level of
      the internal exposure.

PMID- 9582948
TI  - Asbestos-related lung cancer mortality in Piedmont, Italy.
AB  - This study investigates the association between pleural neoplasm mortality, a
      possible proxy for asbestos exposure, and lung cancer mortality among males
      resident in Piedmont (northwestern Italy). Pleural neoplasm mortality was
      estimated in the 1,209 municipalities of the region for the period 1980-1992,
      applying Bayesian methods. The association with lung cancer mortality for
      municipalities was studied using Poisson regression. Urban/rural indicators and
      altitude were also included in the analysis. A positive, statistically
      significant association was found between pleural neoplasm and lung cancer
      mortality (beta = 0.025, P < 0.001); lung cancer risk was associated also with
      urban status (vs. rural, beta = 0.223, P < 0.001) and altitude (P = 0.01). The
      proportion of lung cancer deaths attributable to living in municipalities with
      increased pleural neoplasm mortality was 3.9% (95% confidence interval, 2.1
      5.7%). The observed association and the presence of a dose-response relationship
      at the municipality level underscore the dangers of asbestos for human health.

PMID- 9582949
TI  - Prevalence of infectious diseases and associated symptoms in wastewater treatment
      workers.
AB  - Wastewater treatment workers (WWTW) are potentially exposed to a variety of
      infectious agents and toxic materials. We conducted a retrospective
      epidemiological study to examine the prevalence of infectious diseases and
      associated symptoms in WWTW. From a possible 242 WWTW, 150 completed a
      questionnaire that provided data pertaining to the diagnosis of an infectious
      disease or the prevalence of associated symptoms over a 12-month period.
      Comparison data were obtained from questionnaires completed by 54 college
      maintenance and oil refinery workers. The WWTW exhibited a significantly higher
      prevalence of gastroenteritis, gastrointestinal symptoms (specifically abdominal
      pain), and headaches. No significant differences were found with regard to
      respiratory and other symptoms. Employees classified by exposure categories did
      not exhibit significant differences in the prevalence of symptoms. While
      significant differences were found with regard to the health status of WWTW and
      controls, it appears that these risks are confined to symptoms and infectious
      diseases associated with the gastrointestinal system and are not inclusive of all
      such symptoms or diseases.

PMID- 9582950
TI  - Comparison of dual-energy x-ray absorptiometry and measurement of total body
      water content by deuterium oxide dilution for estimating body composition in
      dogs.
AB  - OBJECTIVE: To compare percentage of body fat (%BF) estimates from dual-energy x
      ray absorptiometry (DEXA) with those derived from total body water (TBW)
      determination by deuterium oxide (D2O) dilution. ANIMALS: 31 healthy, adult,
      purebred dogs of various ages and breeds (body weight, 15 to 39 kg). PROCEDURE:
      The TBW was measured by D2O dilution and subsequent analysis via nuclear magnetic
      resonance (NMR). Blood was collected before and 2 hours after IV administration
      of 275 mg of D2O/kg of body weight. Plasma was separated and stored at -30 C
      until analysis by deuterium NMR. The DEXA scans were obtained immediately after
      blood collection from dogs under general anesthesia. RESULTS: Measurements of %BF
      by DEXA averaged 15.8% higher than calculated estimates of TBW content by D2O
      dilution. The linear regression of %BF by TBW content on %BF by DEXA had a slope
      of 1.04 and a correlation coefficient of 0.84, indicating excellent relative
      agreement between methods despite the significant difference in absolute
      agreement between the 2 methods. The average difference between methods did not
      differ by breed, sex, body condition score, body weight, or %BF, as measured by
      DEXA. CONCLUSION: Comparability of our data with those of previous studies
      suggest that DEXA is useful for in vivo estimation of body composition in healthy
      dogs. Body fat estimated by D2O dilution will be less than that determined by
      DEXA, despite excellent relative agreement between methods.

PMID- 9582951
TI  - Evaluation of a diagnostic monoclonal antibody-based capture enzyme-linked
      immunosorbent assay for detection of a 26- to 28-kd Fasciola hepatica
      coproantigen in cattle.
AB  - OBJECTIVE: To develop a monoclonal antibody-based capture ELISA for detection of
      a 26- to 28-kd coproantigen of Fasciola hepatica in the feces of infected cattle.
      ANIMALS: 27 crossbred yearling calves, 2 New Zealand White rabbits. PROCEDURE: A
      capture ELISA that uses a previously described monoclonal antibody (MAB)
      M2D5/D5F10 was developed. The MAB was used to capture the antigen from the feces,
      and hyperimmune rabbit serum raised against the purified 26- to 28-kd
      glycoprotein was used to detect the coproantigen. This test was used for the
      detection of the antigen in the feces of 27 experimentally infected calves with
      known numbers of flukes. Fecal specimens obtained before infection from the same
      calves were used as negative controls. RESULTS: The assay results identified all
      calves infected with more than 10 flukes at necropsy, and as little as 300 pg of
      coproantigen/ml of fecal supernatant was detected. The assay results correlated
      well with the number of flukes, suggesting that it is possible to estimate fluke
      burden. Infections as early as 6 weeks duration were detected, before flukes
      mature to adults and start to shed eggs. CONCLUSIONS: In experimentally infected
      calves, the coproantigen capture ELISA was more sensitive and easier to perform
      than microscopic examination for the diagnosis of F hepatica infection; moreover,
      6-week-old prepatent infections were detectable. CLINICAL RELEVANCE: This capture
      ELISA containing an F hepatica 26- to 28-kd coproantigen is a quantitative assay
      that is more sensitive than fecal egg counting. In addition, the assay is rapid,
      easy to perform and lends itself well to large numbers of samples. Because it is
      antigen based, the ELISA may be useful for diagnosis of F hepatica infection in
      other species, including human beings.

PMID- 9582952
TI  - Chromogenic assays for equine coagulation factors VII, VIII:C, IX, and X, and C1
      esterase inhibitor.
AB  - OBJECTIVES: To adapt manual human chromogenic assays for coagulation factors VII
      (F.VII), VIII:coagulant (F.VIII:C), IX (F.IX), and X (F.X), and C1-esterase
      inhibitor (C1-INH) for use with an automated analyzer, and to measure the
      activity of these proteins in horses. ANIMALS: 10 healthy horses were used to
      determine ranges for the assays. Pooled plasma for standards was collected from
      an additional 20 healthy horses. PROCEDURE: A computer-assisted analyzer was
      programmed from the manual method for commercially available human F.VII,
      F.VIII:C, F.IX, F.X, and C1-INH chromogenic assay kits. Standards were prepared
      from pooled citrated equine plasma for the F.VII, F.VIII:C, and F.X assays, and
      from commercial pooled citrated human plasma for F.IX and C1-INH assays. RESULTS:
      Mean +/- SD activities in citrated equine plasma from 10 horses were 226 +/- 19%
      for F.VII; 209 +/- 31% for F.VIII:C; 149 +/- 38% for F.IX; 88 +/- 12% for F.X;
      and 18.4 +/- 8.4% for C1-INH. Intra-assay coefficients of variation (CV) were
      5.3% for F.VII; 2.1% for F.VIII:C; and 3.0% for C1-INH. Interassay CV were 5.7%
      for F.VII; 7.4% for F.VIII:C; 3.8% for F.IX; 14.4% for F.X; and 22.0% for C1-INH.
      CONCLUSIONS: Human chromogenic assay kits can be automated and used to measure
      F.VII, F.VIII:C, F.IX, F.X, and C1-INH activities in citrated equine plasma.
      CLINICAL RELEVANCE: Human chromogenic assays can be routinely used to measure
      F.VII, F.VIII:C, F.IX, F.X, and C1-INH in horses, and may be useful in evaluation
      of horses with disorders of hemostasis.

PMID- 9582953
TI  - Analysis of coagulation proteins as acute-phase reactants in horses with colic.
AB  - OBJECTIVES: To measure coagulation factor VIII:coagulant (F.VIII:C) and C1
      esterase inhibitor (C1-INH), hemostasis-associated acute-phase reactant proteins
      and coagulation factors VII (F.VII), IX (F.IX), and X (F.X), hemostasis proteins
      not associated with an acute-phase response, in a select population of horses
      with colic and hemostasis abnormalities, and presumed to have acute-phase
      changes. To compare these values and other routine hemostasis test results in the
      horses with colic with values for a population of healthy horses. To correlate
      the values of known equine acute-phase reactants, F.VIII:C and fibrinogen, to
      those of other tests of hemostasis. To identify hemostasis-associated acute-phase
      reactant proteins and gain insights into the effects the acute-phase response has
      on hemostatic abnormalities in horses with colic syndrome. SAMPLE POPULATION: 54
      plasma samples from horses with colic attributable to inflammatory (n = 39) or
      strangulating (n = 15) intestinal disorders. PROCEDURE: Plasma samples were
      evaluated for activities of F.VII, F.VIII:C, F.IX, F.X, C1-INH, antithrombin III,
      protein C, plasminogen, and alpha 2-antiplasmin (alpha 2AP); fibrinogen
      concentration; and prothrombin (PT) and activated partial thromboplastin (APTT)
      times. RESULTS: Horses with colic had significantly higher fibrinogen
      concentration, greater alpha 2AP and protein C activities, and longer PT and APTT
      than did healthy horses. Horses with colic also had significantly lower mean
      F.VII activity than did healthy horses. Significant positive correlations between
      fibrinogen concentration and F.VIII:C, C1-INH, and alpha 2AP values, and between
      F.VIII:C activity and fibrinogen, C1-INH, alpha 2AP, and plasminogen values were
      identified. CONCLUSIONS: An acute-phase response contributes to changes observed
      in coagulation proteins in horses with colic attributable to inflammatory and
      strangulating intestinal disorders. The data suggest that plasminogen, alpha 2AP,
      and C1-INH, should be considered equine acute-phase proteins.

PMID- 9582955
TI  - Immunohistochemical characterization of immunoglobulin-containing cells and T
      cells in the colonic mucosa of healthy dogs.
AB  - OBJECTIVES: To quantitate numbers of immunoglobulin (Ig)-containing cells (IgA,
      IgG, and IgM) and T cells (CD3+, CD4+, and CD8+) in the colonic mucosa of healthy
      dogs, and to determine whether mean cell numbers differ among colonic regions.
      ANIMALS: 10 clinically normal young adult mixed-breed dogs. PROCEDURE:
      Endoscopically obtained specimens of ascending, transverse, and descending
      colonic mucosa were stained specifically for IgA, IgG, and IgM heavy chains and T
      cell antigens, CD3+, CD4+, and CD8+, using immunoperoxidase techniques.
      Morphometric analysis, performed by light microscopy, was used to quantitate
      numbers in these standardized areas of colonic mucosa. Data analysis allowed
      determination of mean cell numbers in each colonic region, as well as comparison
      of mean cell numbers among colonic regions. RESULTS: The CD3+ and CD8+ T cells
      were the predominant immune cell types in all colonic regions. In the mucosa,
      CD3+ T cells were significantly (P < 0.05) more numerous than CD8+ T cells, and
      CD8+ T cells were significantly (P < 0.05) more numerous than CD4+ T cells. The
      IgA-containing cells were significantly (P < 0.05) more numerous than IgG
      containing cells, whereas IgM-containing cells were least numerous (P < 0.05).
      Differences in mean cell counts among colonic regions were not significant for Ig
      containing cells or T cells. CONCLUSIONS: Mean numbers of immune cells did not
      differ significantly among colonic regions in healthy dogs, although differences
      existed in mean populations of T cells and Ig-containing cells. The CD3+ and CD8+
      T cells were the most numerous immune cell types in colonic mucosa. CLINICAL
      RELEVANCE: These quantitative data provide a basis for study of alterations in
      populations of mucosal immune cells and their possible contribution to the
      pathogenesis of gastrointestinal tract disease.

PMID- 9582954
TI  - Venezuelan field trials of vaccines against brucellosis in swine.
AB  - OBJECTIVE: To evaluate live attenuated Brucella abortus RB51, killed B suis
      cells, O-polysaccharide (OPS) from B abortus 1119-3 and OPS from B suis 1330, for
      protection of swine against B suis challenge exposure under farm conditions.
      ANIMALS: 10 infected boars, 160 unvaccinated control sows and their 1,040
      progeny, and 610 vaccinated sows and their 6,600 progeny. PROCEDURE: Gilts (45 to
      65 days or 4 to 6 months old) were vaccinated or not vaccinated. For the latter
      gilts, additional variables studied were dose, number of doses, and delivery
      route. Mature gilts were mated with 4 infected boars, then serologic reaction to
      Brucella spp, results of bacteriologic culture of vaginal secretions, presence of
      abortion, and litter size were assessed. Various tissues obtained from aborted
      fetuses were obtained for culture of Brucella spp. RESULTS: About 40% of
      unvaccinated control gilts seroconverted to Brucella spp, 27% were positive for
      OPS precipitation by use of agar gel immunodiffusion, 23% aborted their fetuses,
      and the remaining gilts had litters of 5 to 8 pigs. Killed B suis cells provided
      the following protection: 25% of vaccinates were seropositive, 5% had positive
      results of agar gel immunodiffusion, 5% aborted, and the remaining gilts had
      litters of 7 to 8 pigs. Gilts that received live RB51 or OPS vaccine were
      protected. Serologic reactions were always negative, abortion did not occur
      (i.e., 100% were protected), and litter size was 10 to 12 pigs. CONCLUSIONS: Live
      attenuated B abortus RB51 or purified OPS was effective in protecting gilts
      against B suis infections. Dose (10(6) to 10(9) cells, 100 to 500 micrograms,
      respectively), number of doses (1 or 3), or route (IM or PO) made little
      difference. Further research is required to determine why these 2 vaccine
      candidates are similar in protection effectiveness and whether they can be used
      after infection as a treatment.

PMID- 9582956
TI  - Demonstration of a capsule on Mycoplasma ovipneumoniae.
AB  - OBJECTIVE: To examine Mycoplasma ovipneumoniae for presence of a capsule and its
      potential role in adherence. SAMPLE POPULATION: 17 isolates of M ovipneumoniae
      and 2 isolates of M arginini, recovered from sheep with respiratory tract
      disease. PROCEDURE: Mycoplasmas were cultured in modified Fills broth medium,
      ovine fetal lung cells, or ovine tracheal ring explants. Pelleted mycoplasmas or
      ring cultures infected with mycoplasmas were treated with ruthenium red or
      polycationic ferritin and visualized by transmission electron microscopy.
      Reactivity of several lectins with the mycoplasmas was studied by use of a
      microtitration plate agglutination test. RESULTS: Electron microscopy revealed a
      large number of M ovipneumoniae cells covered with an electron dense-stained
      amorphous material suggesting that it was a capsule. Multiple passages of the
      microorganisms in modified Friis broth medium decreased thickness of the capsule,
      but not percentage of cells encapsulated. Marked differences were observed when M
      ovipeumoniae isolates grown in modified Friis broth medium or co-cultured with
      ovine fetal lung cells were compared for capsular thickness or percentage of
      encapsulation. In thin sections of ruthenium red-stained tracheal ring cultures,
      the mycoplasmas appeared to be in close contact with cilia through their capsule.
      All isolates of M ovipneumoniae reacted strongly with wheat germ agglutinin
      lectin. CONCLUSIONS: Mycoplasma ovipneumoniae produces a polysaccharide capsule
      with variable thickness that is dependent on culture conditions and strain.
      Morphologic observations suggest that this capsule facilitates adherence of the
      organism to ciliated epithelium.

PMID- 9582957
TI  - Dynamics of cell-associated viremia and antibody response during the early phase
      of lentivirus infection in sheep.
AB  - OBJECTIVE: To determine patterns of cell-associated viremia and antibody
      responses during the early phase of ovine lentivirus (OvLV) infection in sheep.
      ANIMALS: 18 neonatal lambs. PROCEDURES: 12 lambs were inoculated intratracheally
      with OvLV within 24 hours after birth; 6 lambs were inoculated with noninfected
      cell culture supernatant. Degree of cell-associated viremia was measured every
      other week for 16 weeks by use of a limited dilution assay. Antibody responses to
      OvLV transmembrane (TM) and p25 proteins were determined weekly by use of
      recombinant ELISA. Neutralizing antibody responses were measured before and 8 and
      16 weeks after inoculation. RESULTS: Degree of cell-associated viremia peaked
      between 2 and 6 weeks after inoculation and then decreased. For inoculated lambs,
      mean anti-p25 titer peaked 5 weeks after inoculation then slowly declined,
      whereas mean anti-TM and neutralizing antibody titers increased steadily. Over
      time, mean degree of cell-associated viremia was negatively correlated with mean
      anti-TM titer. Maximum individual degree of cell-associated viremia was
      positively correlated with maximum individual anti-TM titer. CONCLUSIONS: Results
      suggest that after experimental inoculation, OvLV replicates actively for several
      weeks and that an increase in anti-TM titer coincides with a decrease in degree
      of cell-associated viremia. Although the role antibodies play in protecting
      against lentivirus infection remains uncertain, understanding the dynamics of the
      antibody response may have important implications for diagnosis of OvLV
      infection, and antibodies may prove to be valuable markers for prediction of
      infection and disease.

PMID- 9582958
TI  - Assessment of intestinal function in cats with chronic diarrhea after infection
      with feline immunodeficiency virus.
AB  - OBJECTIVE: To identify consistent relevant mechanisms of small intestinal
      dysfunction in cats with experimentally induced feline immunodeficiency virus
      infection (FIV) that developed chronic diarrhea during the time they were being
      used in studies of pathogenicity and transmission of FIV. ANIMALS: 10 cats.
      PROCEDURE: The following investigative tests and techniques were performed on
      each of the cats: routine hematologic and serum biochemical analyses; urinalysis;
      fecal parasitologic and microbiologic examinations; breath hydrogen lactulose
      (BH2LT) and xylose (BH2XT) tests; intestinal permeability test; endoscopic
      examination of the intestinal mucosa; bacteriologic culture of endoscopically
      collected small intestinal juice; and histologic examination of endoscopically
      obtained intestinal biopsy specimens. RESULTS: Neutrophilia was evident in 3
      cats, and lymphopenia was detected in 2 cats. Serum biochemical abnormalities
      were not observed. Urinalysis results were unremarkable. Fecal bacteriologic and
      parasitologic results were normal, except for isolation of Campylobacter sp from
      1 cat. Abnormal BH2XT values suggestive of D-xylose malabsorption were identified
      in 2 cats, and BH2LT values indicated evidence of small intestinal bacterial
      overgrowth in 1 cat. Finally, permeability test results, quantitation of
      bacterial flora from the proximal part of the small intestine and histologic
      examination of biopsy specimens did not reveal any abnormalities. CONCLUSIONS:
      Enteric pathogens did not account for the development of diarrhea in cats with
      experimentally induced FIV infection, and consistent relevant mechanisms of small
      intestinal dysfunction were not identified.

PMID- 9582959
TI  - Protein and calorie effects on progression of induced chronic renal failure in
      cats.
AB  - OBJECTIVE: To determine effects of dietary protein and calories on progression of
      induced chronic renal failure in cats. ANIMALS: 28 young adult female cats.
      PROCEDURE: Renal mass was reduced surgically, and glomerular filtration rate
      (GFR) was determined. Cats were alloted to 4 groups of 7 with similar mean GFR
      (1.52 to 1.55 ml/min/kg of body weight). Diets were formulated to provide: low
      protein and calorie (diet A), low protein and high calorie (diet B), high protein
      and low calorie (diet C), and high protein and calorie (diet D) intakes. Cats
      were fed their prescribed diet for 12 months, then blood and urine biochemical
      variables were measured, after which kidney specimens were examined
      microscopically. RESULTS: Protein intake by cats of groups C and D (9.0 g/d/kg)
      was substantially greater than that by cats of groups A and B (5.3 and 5.2
      g/d/kg, respectively). Caloric intake by cats of groups B and D (73 and 71
      calories/d/kg, respectively) was greater than that by cats of groups A and C (58
      and 55 calories/d/kg, respectively). Renal glomerular lesions were mild and not
      affected by protein, calories or their interactions. Nonglomerular lesions,
      though mild, were significantly influenced by calorie intake, but not by protein
      or calorie-protein interactions. The GFR did not decrease in any group. Urine
      protein-to-creatinine ratio increased significantly in all groups after reduction
      of renal mass, but values from all groups remained within the reference range (0
      to 0.3). CONCLUSIONS AND CLINICAL RELEVANCE: Diets replete in protein were not
      associated with increased severity of glomerular or nonglomerular renal lesions,
      increased proteinuria, or decreased GFR. Diets replete in calories were not
      associated with increased severity of glomerular lesions, but were associated
      with mild increase of nonglomerular lesions. Factors other than protein and
      calorie intake must be considered potential causes of progression of renal
      failure in cats. Results raise questions about the practice of restricting
      quantity of protein in the diet of cats with chronic renal failure, with the
      intention of ameliorating development of further renal damage.

PMID- 9582960
TI  - Humoral and cell-mediated immune responses of beef and dairy cattle
      experimentally infested with Psoroptes ovis.
AB  - OBJECTIVE: To compare cellular and humoral immune responses of beef (Belgian
      White and Blue [BWB]) and dairy (Friesian-Holstein [FH]) cattle to Psoroptes ovis
      infestation and to determine whether P ovis infestation impaired immune responses
      to infectious bovine rhinotracheitis virus (IBR) vaccine or an immunogenic
      protein (keyhole-limpet hemocyanin [KLH]). ANIMALS: 19 BWB and 6 FH 1-year-old
      calves. PROCEDURE: 2 trials were performed. In each trial, 7 (trial 1) or 6
      (trial 2) BWB calves and 3 FH calves were experimentally infested with P ovis and
      3 BWB calves were maintained as uninfested controls. Animals were inoculated with
      KLH and IBR virus vaccine twice; 3 BWB calves in each trial were treated with
      ivermectin. Serum antibody responses to KLH, IBR virus, and P ovis were measured
      by use of ELISA. A lymphocyte transformation assay was used to determine
      nonspecific responses to 3 mitogens and specific lymphocyte reactivity to P ovis
      antigen. RESULTS: In each trial, 3 BWB and 3 FH calves developed clinical signs
      of psoroptic mange and mites could be recovered. Infested and control animals
      developed similar antibody titers to KLH and IBR virus. Antibodies to P ovis were
      detected early in some infested calves, and this was correlated with a marked
      cell-mediated immune response. Lymphocyte responsiveness to the 3 mitogens was
      not significantly different among groups. CONCLUSIONS: In these calves,
      infestation with P ovis induced a marked humoral and cell-mediated immune
      response. Immunosuppression was not evident.

PMID- 9582961
TI  - In vivo effect of Pasteurella haemolytica infection on bovine neutrophil
      morphology.
AB  - OBJECTIVE: To determine whether characteristic changes in neutrophil morphology
      caused in vitro by Pasteurella haemolytica leukotoxin (LKT) can be observed in
      vivo by electron microscopic examination of infected tissue chamber fluids and
      pneumonic lungs. ANIMALS: 7 mixed-breed beef calves. PROCEDURE: Tissue chambers
      were implanted subcutaneously in 3 calves and were inoculated with P haemolytica
      or phosphate-buffered saline solution. Chamber fluid samples, obtained at 8 and
      32 hours after inoculation, were examined, using electron microscopy.
      Experimental pneumonia was induced in an additional 4 calves by transthoracic
      inoculation with P haemolytica. These calves were euthanatized at 6, 12, 24, and
      36 hours after inoculation and lung sections were examined, using transmission
      electron microscopy. RESULTS: On examination, using transmission electron
      microscopy, neutrophils in lung sections and tissue chamber fluids had
      cytoplasmic and nuclear changes indicative of irreversible cell injury, including
      cell swelling, loss of plasma membrane ruffling, mitochondrial swelling,
      autolytic vacuolation, disruption of plasma membrane, nuclear pyknosis,
      karyolysis, and karyorrhexis. On examination, using scanning electron microscopy,
      leukocytes obtained from tissue chambers did not have their typical convoluted
      surfaces, but appeared rounded and swollen or shrunken with pitted surfaces.
      CONCLUSIONS: Pasteurella haemolytica-induced changes in neutrophil morphology in
      vivo were similar to those previously induced by in vitro exposure of neutrophils
      to LKT. Changes were suggestive of injury initiated by damage to the plasma
      membrane, which is consistent with the mechanism of action of pore-forming
      cytolysins. CLINICAL RELEVANCE: Pasteurella haemolytica LKT appears to be an
      important virulence factor in vivo; a fact that should be addressed in the
      development of vaccines.

PMID- 9582962
TI  - Development and use of an enzyme-linked immunosorbent assay to monitor serum and
      urine acepromazine concentrations in thoroghbreds, and possible changes
      associated with exercise.
AB  - OBJECTIVES: To develop an ELISA that is sensitive and suitable for measurement of
      immunoreactive acepromazine (ACP) in horse serum and urine and to determine the
      acute effects of exercise on immunoreactive ACP values in Thoroughbreds. ANIMALS:
      12 healthy Thoroughbreds (5 mares, 5 geldings, 2 stallions), aged 2 to 8 years.
      PROCEDURE: A commercially available antibody and a horseradish peroxidase
      conjugated oxime derivative of immunoreactive ACP were used to develop a one-step
      ELISA. Horses were used in a crossover design study to evaluate possible effects
      of treadmill exercise on serum and urine ACP concentrations after a single (25
      mg) IM injection of the drug. RESULTS: Immunoreactive ACP was detectable at
      concentrations as low as 50 pg/ml in serum and 100 pg/ml in urine, with intra-
      and interassay variabilities of 1.1 and 5.2%, respectively. The antibody had some
      cross-reactivity with a limited number of other phenothiazines. After drug
      administration, serum ACP immunoreactivity achieved a peak concentration (10.5
      ng/ml) within 30 minutes and could be measured up to 48 hours in serum and 120
      hours in urine. Although exercise had no significant effect on serum drug
      concentration, immunoreactive ACP disappeared more quickly (by 48 hours) from the
      urine of horses in the exercised group. CONCLUSIONS: This one-step ELISA provides
      a simple and sensitive means to measure immunoreactive ACP in equine serum and
      urine. The ability to detect drug several days after administration of a low dose
      of ACP should augment efforts to control illicit use of this drug in performance
      horses. Potential changes in ACP kinetics after exercise warrant further study.

PMID- 9582963
TI  - Cardiopulmonary effects of propofol and a medetomidine-midazolam-ketamine
      combination in mallard ducks.
AB  - OBJECTIVE: To compare safety of propofol with a medetomidine-midazolam-ketamine
      (MMK) combination as an anesthetic agent in mallard ducks. ANIMALS: 12 healthy
      adult female mallard ducks. PROCEDURE: Each duck was anesthetized twice in a
      crossover study design with 5 days between randomized treatments. Ducks were
      given medetomidine (50 micrograms), midazolam (2 mg), and ketamine (10 mg) in
      combination, i.v., or propofol (10 mg, i.v., followed by 1- to 4-mg boluses).
      Systolic, diastolic, and mean arterial pressures, heart and respiratory rates,
      and esophageal temperature were recorded before anesthesia and every 5 minutes
      after induction for 30 minutes, and at 5 minutes after reversal with atipamezole
      (250 micrograms) and flumazenil (25 micrograms; MMK group) or last bolus
      (propofol group). Arterial blood samples from 8 ducks were collected before
      anesthesia, 5, 10, 15, 30 minutes after induction, and after reversal or last
      bolus. RESULTS: 8 ducks survived the MMK anesthesia; 1 duck died and 3 ducks
      required resuscitation to prevent death. All ducks survived propofol anesthesia.
      Ducks anesthetized with either anesthetic agent had a significant increase in
      arterial carbon dioxide tension and decrease in arterial oxygen tension, arterial
      pH, and esophageal temperature. Ducks given MMK had a decrease in mean arterial
      pressure and respiratory rate, whereas ducks given propofol had an increase in
      respiratory rate. Rapid reversal of the effects of MMK was achieved with
      atipamezole and flumazenil. All physiologic variables, except esophageal
      temperature in the propofol group, returned to approximate baseline values after
      reversal or last bolus. CONCLUSIONS: The MMK combination in unsafe for use in
      ducks. Ducks can be anesthetized safely with propofol but should be monitored and
      ventilated artificially.

PMID- 9582964
TI  - Cardiorespiratory effects of low-flow and closed circuit inhalation anesthesia,
      using sevoflurane delivered with an in-circuit vaporizer and concentrations of
      compound A.
AB  - OBJECTIVES: To determine the concentrations of sevoflurane and compound A (a
      degradation product of sevoflurane) in the anesthetic circuit when sevoflurane
      was delivered with an in-circuit vaporizer, and to determine the
      cardiorespiratory effects of sevoflurane in dogs. ANIMALS: 6 mixed-breed dogs.
      PROCEDURE: In-circuit vaporizers were connected to the inspiratory limb of a
      circle rebreathing system connected to a ventilator. A reservoir bag was attached
      to the Y-piece connector to act as an artificial lung, and sevoflurane
      concentrations in the anesthetic circuit were measured at vaporizer settings of
      1, 3, 5, 7, and 10 and oxygen flow rates of 250 and 500 ml/min. Cardiorespiratory
      effects of sevoflurane were determined in dogs while they were breathing
      spontaneously, during controlled ventilation, and during closed circuit
      anesthesia. Concentrations of compound A were determined by means of gas
      chromatography with flame ionization. RESULTS: The concentration of sevoflurane
      in the anesthetic circuit increased with vaporizer setting and time. For oxygen
      flow rates of 250 and 500 ml/min, vaporizer settings between 5 and 7 and between
      7 and 10, respectively, produced sevoflurane concentrations closest to values
      reported to produce surgical anesthesia in dogs. Significant differences were not
      observed in cardiorespiratory variables with time or among anesthetic conditions.
      Concentrations of compound A in the anesthetic circuit were less than values
      reported to produce renal toxicoses and death in rats. CONCLUSION: Results
      suggested that sevoflurane can be administered to nonsurgically stimulated dogs,
      using an in-circuit vaporizer and low (< 15 ml/kg/min) oxygen flow rates, without
      causing significant cardiorespiratory depression or clinically important
      concentrations of compound A.

PMID- 9582965
TI  - Forelimb joint moments and power during the walking stance phase of horses.
AB  - OBJECTIVE: To calculate normative joint moments of force and power for the
      forelimb of walking horses as a benchmark against which to compare these
      mechanical variables in horses with specific lameness. ANIMALS: 4 Dutch Warmblood
      horses with no recent history of lameness. PROCEDURE: Horses were walked by hand
      through the test area, and data from 5 walking trials were collected for each
      horse. Two camera views were combined with vertical and craniocaudal ground
      reaction forces to calculate net moments of force in the sagittal plane across
      the carpal, metacarpophalangeal (fetlock), and distal interphalangeal (coffin)
      joints during the stance phase of the forelimb. Mechanical power was calculated
      as the product of net joint moment and the joint's angular velocity. RESULTS:
      During the early part of the stance phase, the carpal joint had oscillating
      periods of energy generation and absorption against a predominant flexor moment,
      then an absorption phase at the end of the stance phase, as the carpus flexed
      into swing against an extensor moment. The fetlock absorbed energy in the early
      part of the stance phase, then the terminal part was marked by a large generation
      of energy across the joint. A flexor moment was measured at the coffin joint
      throughout the stance phase, and this coincided with a long phase of energy
      absorption followed by a short phase of generation for push-off. CONCLUSION:
      Consistency of the power data indicates that typical profiles of work exist for
      each of the joints (carpus, fetlock, and coffin). CLINICAL RELEVANCE: Detection
      of changes to these profiles of work may contribute to diagnosis of specific
      lameness conditions.

PMID- 9582966
TI  - Effect of high-intensity exercise on arterial blood gas tensions and upper airway
      and cardiac function in clinically normal quarter horses and horses heterozygous
      and homozygous for hyperkalemic periodic paralysis.
AB  - OBJECTIVE: To determine the effect of exercise on arterial blood gas tensions and
      upper airway and cardiac function in clinically normal Quarter Horses and horses
      heterozygous and homozygous for hyperkalemic periodic paralysis (HYPP). ANIMALS
      AND PROCEDURE: 5 clinically normal Quarter Horses, and 5 heterozygous and 2
      homozygous HYPP-affected horses were examined before, during, and after exercise
      on a high-speed treadmill. Arterial blood gas tensions, ECG, and echocardiogram
      were obtained prior to exercise. Upper airway endoscopy, collection of arterial
      blood samples, and continuous electrocardiography were performed during a high
      intensity stepwise exercise test. An ECG was obtained within 1-minute after
      completion of the final step. RESULTS: None of the horses homozygous or
      heterozygous for HYPP had signs of weakness or muscle fasciculations before,
      during, or after exercise. Horses homozygous for HYPP had intermittent
      laryngospasm, dynamic pharyngeal collapse, and appreciable hypoxemia,
      hypercapnia, and ventricular premature contractions during exercise. Heterozygous
      and clinically normal horses did not have any abnormalities. Potassium
      concentration increased significantly above the baseline reference range during
      exercise in all groups of horses. CONCLUSIONS: Horses homozygous for HYPP had
      laryngospasm and dynamic pharyngeal collapse associated with exercise, most
      likely secondary to increase in potassium concentration. Upper airway dysfunction
      is the most likely cause of hypoxemia and hypercapnia. Cardiac arrhythmias were
      most likely caused by a combination of hypoxemia and hyperkalemia.

PMID- 9582967
TI  - Effect of xylazine, detomidine, and a combination of xylazine and butorphanol on
      equine duodenal motility.
AB  - OBJECTIVE: To evaluate the effect on equine duodenal motility of some analgesic
      agents commonly used to treat colic. ANIMALS: 4 healthy adult healthy horses--2
      mares and 2 geldings--which were carrying an indwelling gastric cannula made of
      silastic rubber. One horse also carried 2 long-term indwelling bipolar electrodes
      that had been sutured onto the duodenum and jejunum. PROCEDURE: To ensure an
      empty stomach, solid food was withheld from horses for around 20 hours prior to
      an experiment. Using videoendoscopic guidance, an 8-F catheter with 3 small,
      discrete pressure sensors was passed through the gastric cannula and directed
      into the proximal portion of the duodenum. Deflection of the recording pen, to
      which the catheter was attached, indicated a motile event in that section. Drugs
      (treatment) were given into the jugular vein in a randomized block design, 1
      treatment/experiment, after a 1-hour baseline recording. Treatments were: 2 ml of
      0.9% NaCl, xylazine (XYL, 0.5 mg/kg of body weight), detomidine (DET, 0.0125
      mg/kg), or a xylazine/butorphanol combination (XYB, 0.5/0.05 mg/kg). Each horse
      received each treatment twice. All positive pressure peaks > 5 mm of Hg recorded
      from the most proximal sensor on the catheter were counted in 15-minute blocks.
      Each mean 15-minute posttreatment value was compared with the baseline value for
      that specific treatment. RESULTS: There was no significant difference between
      baseline values. All treatments significantly (P < 0.05) reduced frequency of
      pressure peaks below their respective pretreatment values, but to variable
      degrees and durations. Comparatively, XYL had the least effect, with mild, though
      significant, reduction for only the first 30 posttreatment minutes; DET and XYB
      caused a significant marked reduction for 1 hour after treatment. CONCLUSIONS:
      The profound suppressive effect of a routine dose of detomidine or
      xylazine/butorphanol combination on equine duodenal motility must be considered
      when using these agents for management of colic, especially when encouragement of
      intestinal motility is desirable.

PMID- 9582968
TI  - Urolithiasis in dogs. I: Mineral prevalence and interrelations of mineral
      composition, age, and sex.
AB  - OBJECTIVE: To compile and statistically analyze selected data from a large number
      of canine urinary calculi. SAMPLE POPULATION: 11,000 specimens: 5,781 from female
      dogs, 5,215 from male dogs, and 4 from dogs of unrecorded sex. PROCEDURE: Records
      were used to compile information from all canine calculi analyzed between July
      1981 and January 1994. Interrelations of mineral composition, location of
      specimens within the urinary tract, age and sex of affected dogs, and number of
      previous episodes of urolithiasis were determined. RESULTS: Approximately 70% of
      the specimens were from a first episode of urolithiasis. Calculi were located in
      the urinary bladder of 93.1% of females and 79.0% of males, and in the upper
      urinary tract of 4% of females and 2% of males. Calculi were found in multiple
      sites in 23.1% of males and 5.2% of females. Significantly higher proportions of
      struvite, apatite, and urate were found in uroliths from females; oxalate,
      cystine, silica, and brushite were significantly more prevalent in males. Sixty
      one percent of specimens from males and 29% from females were composed of a
      single mineral substance. The most common mineral combination of 2 or more
      minerals included struvite and apatite. An additional 67 specimens from male dogs
      and 49 from female dogs contained other mineral combinations. In 48% of specimens
      from males and nearly 62% of specimens from females, the minerals formed several
      distinct layers of differing composition. CONCLUSIONS: Male and female dogs from
      urinary calculi composed of 1 or more of several distinct minerals. Prevalence of
      canine uroliths differs between ages and between the sexes. Many specimens
      contain complex layering of minerals; most specimens were found in the urinary
      bladder. CLINICAL RELEVANCE: Sex and age of dogs, mineral types of likely calculi
      in males versus females, and their anatomic location are important considerations
      for clinicians when evaluating risk in dogs with urolithiasis.

PMID- 9582969
TI  - Urolithiasis in dogs. II: Breed prevalence, and interrelations of breed, sex,
      age, and mineral composition.
AB  - OBJECTIVE: To analyze selected breed-related data for canine urinary calculi.
      SAMPLE POPULATION: 11,000 specimens: 5,781 from female dogs, 5,215 from males,
      and 4 from dogs of unrecorded sex. PROCEDURE: Information was compiled for all
      canine urinary calculi submitted between July 1981 and January 1994. Results for
      a mixed-breed group and 26 of the most common breeds of stone-forming dogs were
      analyzed. Interrelations of breed, sex, and age of affected dogs and mineral
      composition of the specimens were determined. RESULTS: Prevalence of 5 specific
      mineral types was significantly correlated between the sexes of 27 common breed
      groups: struvite, calcium phosphate (apatite), calcium oxalate, brushite, and
      urate. Struvite-containing calculi were seen in high proportions in both sexes of
      7 breeds, and in low proportions in both sexes of 7 other breeds. Male and female
      Lhasa Apsos, Cairn Terriers, and 5 other breeds had high proportions of oxalate
      containing calculi; values in males were substantially higher. Low numbers of
      oxalate-containing calculi were seen in both sexes of 7 breeds; Dalmatians had
      the lowest numbers. Males and females of 6 breeds had high numbers of urate
      containing calculi, Dalmatians and English Bulldogs had the highest numbers. Low
      amounts of urate were found in calculi from males and females of 6 breeds,
      Samoyeds had the lowest numbers. Highest proportions of cystine-containing
      calculi were seen in male Dachshunds, English Bulldogs, and Chihuahuas. Males of
      8 breeds had no specimens that contained cystine; only 2 such specimens were
      obtained from females. CONCLUSIONS: Prevalence of uroliths differs among breed,
      age, and sex of affected dogs. CLINICAL RELEVANCE: Breed, sex, and age of dogs;
      mineral types of calculi in males versus females; and their anatomic location
      within the tract are important considerations for clinicians when evaluating risk
      in dogs with urolithiasis and in identifying areas that need further in-depth
      applied or clinical investigation, or both.

PMID- 9582970
TI  - Urolithiasis in dogs. III: Prevalence of urinary tract infection and
      interrelations of infection, age, sex, and mineral composition.
AB  - OBJECTIVE: To compile and statistically analyze selected data from a large number
      of canine urinary calculus specimens that were subjected to quantitative, layer
      by-layer mineral analysis. SAMPLE POPULATION: 11,000 canine urinary calculus
      specimens. 5,781 from female dogs, 5,215 from male dogs, and 4 from dogs of
      unrecorded sex. PROCEDURE: Records of the Urinary Stone Analysis Laboratory,
      School of Veterinary Medicine, University of California were used to compile
      information regarding all canine urinary calculus specimens submitted for
      analysis between July 1981 and January 1994. Interrelations of sex and age of the
      affected dogs, mineral composition of the specimens, and associated urinary tract
      infections were analyzed statistically. RESULTS: Urolithiasis was associated with
      growth of bacteria isolated from urine or calculi, or both, in 65% of females and
      nearly 44% of males. Staphylococcus intermedius was isolated most often from
      either sex (54% for females, 30% for males). In addition to staphylococci, 22
      other bacterial species were isolated from specimens from females, and 17 other
      bacterial species and 1 species of yeast were isolated from males. A single
      bacterial species was isolated from 87.6% of cultures from females and from
      nearly 90% of cultures from males. Among females, nearly 98% of pure cultures of
      staphylococci were associated with calculi that contained struvite; this was true
      for 80% of pure cultures of staphylococci from males. CONCLUSIONS AND CLINICAL
      RELEVANCE: There are wide sex differences in prevalence of urolithiasis- and
      specific mineral-associated bacterial infections. In several instances, bacterial
      infections were significantly related to urinary calculus location. These
      variables should be considered in any evaluation of canine patients that have
      uroliths.

PMID- 9582971
TI  - Urolithiasis in dogs. IV: Survey of interrelations among breed, mineral
      composition, and anatomic location of calculi, and presence of urinary tract
      infection.
AB  - OBJECTIVE: To compile and analyze selected data from a large number of canine
      urinary calculus specimens that were subjected to quantitative, layer-by-layer
      mineral analysis. SAMPLE POPULATION: 11,000 canine urinary calculus specimens:
      5,781 from female dogs, 5,215 from male dogs, and 4 from dogs of unrecorded sex.
      PROCEDURE: Records of the Urinary Stone Analysis Laboratory, School of Veterinary
      Medicine, University of California were used to compile information regarding
      urinary calculus specimens from dogs. Records surveyed were of all canine calculi
      submitted for analysis between July 1981 and January 1994. Results analyzed
      included those of a mixed-breed group and 26 common breeds of stone-forming dogs.
      Interrelations of breed, sex, and age of the affected dogs, mineral composition
      of the specimens, and associated urinary tract infections were analyzed
      statistically. RESULTS: Proportions of culture-positive specimens were
      significantly correlated between the sexes (r = 0.494, P = 0.008). Staphylococcus
      intermedius was isolated most often from either sex, ranging from 36.1% (Basset
      Hounds) to 67.9% (Pekingese) of cultured specimens from females and 8.7%
      (Chihuahuas) to 71.4% (Scottish Terriers) of specimens from males. The second
      most frequently isolated bacterial species, Escherichia coli, ranged from 0% in
      males of 2 breeds and females of 4 breeds to 25% in Cairn Terrier males and 19.4%
      in Basset Hound females. Streptococcus spp were the third most frequently
      isolated bacterial species. Significant correlations between the sexes were found
      for percentages of calculi located in the urinary bladder (r = 0.490, P = 0.008),
      and for calculi voided in the urine (r = 0.503, P = 0.006). CONCLUSIONS: Breed
      and sex differences in prevalence of urolithiasis- and mineral-associated
      bacterial infections are numerous. Staphylococcus intermedius was the most common
      isolate from specimens from all but 3 of 54 breed/sex groupings. For either sex,
      streptococcal infections were significantly related to proportions of calculi
      passed in the urine.

PMID- 9582972
TI  - [About suicide methods of physicians, medical personnel and related professions].
AB  - A collective of 131 suicides of physicians (n = 40), female and male nurses (n =
      38), pharmacists/chemist/biologists (n = 17) and medical/chemical assistant
      personnel (n = 36) was evaluated with regard to the method of suicide. Preferred
      methods were ingestion of medicaments orally (29%) and by infusion/injection
      (18%), hanging (13%), cyanide poisoning (10%), jumping from great height (10%)
      and drowning (8%). The results were compared with a control group (n = 739:
      hanging 32%, oral ingestion of medicaments 16%, jumping from great height 13%,
      shooting 9%, drowning 8%, railway suicides 7%). Methods such as
      infusion/injection (anesthesiologists) and cyanide poisoning (chemists/chemical
      staff) being typical of occupation were over-represented within the first group,
      however, at the same time concentrated on specialized subgroups. Intoxications by
      infusion/injection and medicaments predominated even more clearly in physicians
      (58%) than in the total collective. CONCLUSION: The tendency to a method of
      suicide being typical of the profession rises among physicians and related
      occupations with the degree of specialization (increasing knowledge, easier
      access to appropriate drugs and methods). Medical/chemical education and
      occupation alone is not yet associated with such a predisposition.

PMID- 9582973
TI  - [Harpoons--toy, tool, weapon?].
AB  - The case of a 13-year-old boy injured by a Spanish souvenir harpoon is reported.
      Shooting experiments with the harpoon showed that serious injuries can be caused.
      The results are discussed and compared with the rare literature.

PMID- 9582975
TI  - [Immunohistochemical insulin evidence at the injection site].
AB  - Under suspicion on an injection of high doses of insulin with suicidal or
      homicidal intention, the local detection of a vital injection of insulin is
      necessary for the critical examination. The submitted immunohistochemical method
      shows, that: the insulin-specific positive immunoreaction of the subcutaneous
      fatty tissue is assigned to an injection of insulin, although a missing staining
      does not exclude a premortal application of insulin, a widened immunopositive
      intercellular space between the subcutaneous lipocytes as expression of a local
      edema points to the intravitality of the injection of insulin.

PMID- 9582974
TI  - [Death in the bathtub--rectal drug administration].
AB  - A young nurse was found dead in a bathtub. An autopsy revealed the following
      results: pulmonary emphysema, severe edema of both lungs, transudation in both
      pleural cavities. Conspicuous were skin sticks of a white wax material. In
      chemical-toxicological analysis diazepam, tetrazepam and phenobarbital were
      detected in this material. After anal-rectal and additionally oral ingestion the
      following blood concentrations were determined: BAC 0.03/1000; diazepam 500
      ng/ml; nordiazepam 65 ng/ml; tetrazepam 180 ng/ml; phenobarbital 9.4 mg/l. In
      connection with this drug effects an acute, multifocal, suppurating
      bronchopneumonia in both lungs was revealed as the cause of death.

PMID- 9582976
TI  - [Analytical confirmation of error in false positive amphetamine immunoassays and
      results].
AB  - Numerous urine samples were found to be positive when using a new amphetamine
      immunoassay (AxSYM). Confirmation analysis was carried out in a second laboratory
      at "reasonable prices" using a simple TLC-method with non specific ninhydrine
      detection and resulted in many "positive" confirmation findings. The GC/MS
      analysis clearly indicated the absence of amphetamine derivatives regularly
      encountered in forensic toxicology. The false-positive immunochemical findings
      may probably be caused by endogenous substances.

PMID- 9582977
TI  - [Suicidal hanging or simulated suicide? Once again a case of Kobue: a spectacular
      case in the history of Japanese legal medicine].
AB  - The cause of death of a 45-year-old woman named Kobue Hiramatsu became an issue
      in a notable criminal trial called the Kobue-case. The woman and three young
      girls were found dead in Kobue's house at the end of June 1926. The bodies were
      decomposed. The three girls had been strangled, while Kobue was found suspended
      by a waist band tied to a lintel. An open noose had been arranged by winding the
      band twice around the lintel and tying the both ends. The ligature lay
      immediately under the chin. Her feet touched the tatami mat and between feet,
      there were a charcoal brazier and a cutting board. There were two abrasions, not
      parallel with each other, ont he front of her neck. One abrasion was under the
      ligature. The other was about 2 cm below the first and was accompanied by bruise.
      An expert diagnosed that the upper mark without the bruise was produced after
      death, while the lower abrsion was a ligature mark from strangulation, and that
      she was suspended for simulation of suicide after being strangled. A former
      lodger at her house was arrested, but he denied any guilt. The main issue at the
      trial was the nature of the lower mark and the mechanism by which the two marks
      were produced. The defendant was found innocent and acquitted based on the expert
      opinions that the lower mark was a hanging mark and the upper one was produced by
      the upward movement of the ligature when asphyxia-induced convulsion occurred
      during hanging. There was no unanimity on how the body weight affected the neck
      during hanging or what the posture of the body was when convulsion occurred. In
      the present paper, how Kobue hanged herself and what caused the ligature to move
      upward is discussed.

PMID- 9582978
TI  - [Certain aspects of laterality research].
AB  - One-side dominance, known as morphological and functional asymmetry, in the limbs
      a human characteristic that is of genetic or of both genetic and environmental
      origin. There are several aspects investigating laterality in men. Altogether it
      is possible to distinguish morphological and functional asymmetries. A vast range
      of testing techniques have been used to assess handedness. Asymmetry in hand use
      takes two forms: differential hand preference and differential dexterity between
      the hands. Writing hand and self-report are two of the most popular techniques.
      Other preference measures include observation of how people use tools and
      questionnaires. Performance tests assess speed and accuracy in tasks stressing
      manipulative dexterity. Morphologic asymmetries are not so useful for the
      investigation of the handedness. This method should only be used in past mortem
      examinations. The literature on laterality is large, but there are only a few
      studies in the last years concerning the morphologic asymmetries compared to the
      studies on functional asymmetries.

PMID- 9582979
TI  - [The enforceability of expert opinion in theory and practice].
AB  - This article provides a short review of the legal rules in Austria dealing with
      the minimum standards of expert opinions, absolutely necessary for the
      understanding and assessment of the opinion. As shown by an example of a case of
      handwriting investigation experts often ignore even the minimum standards. On the
      other hand judges do not consequently require these standards. This gap between
      theory and practice can only be filled by a thorough and perfect examination and
      by providing specific information to potential clients, given by professional
      associations.

PMID- 9582980
TI  - [Pathology in Russia: where are we going?].
AB  - The history of Russian pathologic anatomy from the postwar time to nowadays is
      briefly reviewed. Negative effects of some legislative acts of the all levels of
      public health, profound financial crisis are shown. Particularly negative were
      consequences of a narrow specialization of medicine which affected also
      pathologic anatomy. Insufficient classical education that includes theoretical
      and prosecutor training of the general profile results in the fall of interest to
      general pathology this having a negative effect on the prestige of this
      profession.

PMID- 9582981
TI  - [Pyo-resorptive fever and wound sepsis].

PMID- 9582982
TI  - [General pathology--an independent medical discipline].
AB  - Recognition of general pathology as an independent discipline is urgent at this
      stage of medical science development. Its contents are basic rules of the origin,
      development and outcomes of human diseases. It is desirable to organize in the
      medical schools chairs (courses) of general pathology as an supradiscipline
      subject the knowledge of which is necessary to the wide circle of students,
      interns, physicians of all specialties.

PMID- 9582983
TI  - [Methodological approaches of I.V. Davydovskii from the standpoint of the
      pathophysiologist].
AB  - I.V. Davydovsky's principles of etiology, pathogenesis and disease are, in fact,
      biological concept of the theory of pathology. The main point of this concept is
      consideration of general pathological processes (regeneration, inflammation,
      thrombosis, immunity, fever, etc.) as adaptive natural-historical events the
      importance of which for an individual may vary in a wide range. A prospective
      direction in further development of I.V. Davydovsky's concept is the study of the
      role of regulation system at various levels in the storage of genetic information
      and its realization. This determines the degree of usefulness of these adaptive
      processes.

PMID- 9582984
TI  - [Senile amyloidosis: from the Schwartz tetrad to the present].
AB  - Senile amyloidosis can be systemic (generalized) or local, this being determined
      by the protein precursor of the amyloid fibrils. Systemic cardiovascular
      amyloidosis should be distinguished from AL-amyloidosis. Senile amyloidosis is
      represented by both endocrine and nonendocrine forms. Endocrine forms include
      isolated auricular amyloidosis and amyloidosis of the Langerhans islands, while
      non-endocrine forms include aortic amyloidosis, cerebral amyloidosis, eye
      amyloidosis and amyloidosis of the prostate and/or seminal vesicles. Most
      frequent are combinations of the endocrine with aortic amyloidosis or Langerhand
      island amyloidosis with cerebral amyloidosis and eye amyloidosis. These data
      reject the Schwarts tetrad as necessary manifestation of senility.

PMID- 9582985
TI  - [Role of tumor necrosis alpha in the regulation of extracellular matrix and
      proliferation of mesangial cells in nephrotoxic nephritis].
AB  - Acute and chronic stages of NTN are followed by infiltration of glomeruli with
      monocytes/macrophages having different location (lumen of capillaries in the
      acute stage and mesangial zone in the chronic one). TNF-alpha is one of the key
      factors of the NTN acute stage damaging glomerular structures and initiating
      production of matrix form of the main factor of the fibroblast growth and
      transforming growth factor beta. Accumulation of these cytokines in the matrix
      facilitated monocyte penetration in the mesangium zone in chronization.
      Interaction of the matrix-associated cytokines regulates proliferative and
      fibrogenic activity of the mesangial cells as well as production of TNF-alpha by
      monocytes/macrophages. A decrease of TNF-alpha level during a chronic stage of
      NTN results in a decrease of the mesangial cell ability to produce matrix
      associated cytokines.

PMID- 9582986
TI  - [The tuberculosis epidemic in a morphologic light].
AB  - Epidemiologic situation with tuberculosis is worsening in Russian Federation.
      Induced pathomorphosis of this disease in the course of its epidemic is
      presented. Unsatisfactory level of therapeutic and diagnostic measures and the
      necessity to develop a unified classification and records of tuberculosis are
      emphasized. Its complications and iatrogenic pathology are shown.

PMID- 9582987
TI  - [Pathogenetic aspects of chronic inflammation].
AB  - Chronic inflammation (CI) was studied immunologically and immunomorphologically
      on biopsy and surgical material: interstitial pulmonary diseases, chronic
      inflammatory processes of the uteri and ovaries, decubitus in the spinal cord
      damage, trophic ulcers of the limbs, osteomyelitis, chronic abscesses of soft
      tissues, coccygeal cysts and chronic paraproctitis. The following parameters
      determine the development of CI: persistence of the damaging agent, immunological
      insufficiency, mechanisms of autoimmunization, progression of CI according to the
      principle of vicious circle. CI looses its biological usefulness as a
      compensatory-adaptive reaction.

PMID- 9582989
TI  - [Pathology of traumatic disease in wounded people].
AB  - The hemodynamic concept of TD pathogenesis and morphogenesis is based on the
      vascular response initiated by neuroendocrine mechanisms. Their effect in grave
      wounds is potentiated by blood loss, shock, endotoxicosis as well as inadequate
      therapy. Secondary damage to organs with clinical syndrome of their failure
      results from impaired correlation between the plasticity of histones and speed of
      microcirculatory alterations. Periodization of TD is suggested that takes into
      account its cyclicity and specificity of time distribution of therapeutic and
      diagnostic actions. Cerebral, pulmonary, renal, cardiac, gastro-intestinal and
      mixed forms of TD are distinguished.

PMID- 9582988
TI  - [Kinetics of vascular wall cells and atherogenesis].
AB  - Similarity of the cell population of atherosclerotic plaques in human arteries
      and immune inflammation foci in various diseases allow to regard atherogenesis as
      a chronic inflammatory reaction similar to the delayed-type hypersensitivity
      reactions.

PMID- 9582990
TI  - [Ultrastructure of the myocardium in patients with cardiac pathology complicated
      by diabetes mellitus].
AB  - Myocardial ultrastructure of patients with diabetes mellitus and cardiomyopathy
      and those with coronary heart disease was practically similar. Alterations of the
      ultrastructural organization concerned mainly the mitochondria and structures
      responsible for the contraction. Disturbances of the microcirculation in diabetes
      were so much pronounced that the presence of the large arteries stenosis did not
      enhance the alterations in the cardiomyocytes: supply of oxygen and substrates to
      the working cells was severely changed because of the arteriolar spasm as well as
      capillaries obturation due to adhesion of blood cells to the endothelial lining
      and low level of micropinocytosis in the endotheliocytes.

PMID- 9582991
TI  - [Visceral toxocariasis].
AB  - A case of the disease in a 6-year-old boy is described. The disease was
      characterized by a long recurrent course with development of a parasitic gumma in
      the mediastinum and arrosion of the descending aorta and the left bronchial wall.
      Pulmonary bleeding was a course of death. Differential diagnosis between
      toxocariasis and askaridosis is given.

PMID- 9582992
TI  - [The 10th revision of the International Classification of Diseases and its use in
      pathology practice].
AB  - Basic features of ICD-10 related to its word-figure structure and its distinction
      from ICD-9 are presented. Definitions of the initial cause of death designed for
      statistical records, some specifications of the antenatal, perinatal, neonatal
      and infantile mortality are included. The criteria of the stillborn and
      viviparous state are formulated. Information concerning the International
      Classification of Tumors is provided. New data in ICD-10 concerning the diseases
      with high lethality are considered.

PMID- 9582993
TI  - [Summary of the work of the Pathology Service of the Moscow Health Committee in
      1996].
AB  - The activity of 57 clinical pathology departments including 2 centers (Moscow
      city center of pathology studies and phthysiopathology center) is summarized.
      31,559 autopsies and about 1.5 million biopsies were performed. Analysis of
      lethal outcomes shows that cardiovascular diseases are the most frequent cause of
      death. Tumors, GI tract diseases, respiratory diseases are at the second, third
      and forth place, respectively. A sharp increase of deaths from tuberculosis is
      observed. The number of diagnosis discrepancy is 16.5% and is stable for the last
      five years. The main problems of pathology service are technical insufficiency
      and lack of staff.

PMID- 9582994
TI  - [Current aspects of acute destructive pancreatitis].
AB  - In acute destructive pancreatitis due to rapidly developing endotoxicosis, marked
      circulatory disturbances, deep disturbance of homeostasis and functional
      insufficiency of vital organs, urgent surgery is necessary in order to remove
      necrotic parts of the pancreas as the main source of heavy toxemia resulting in
      shock and collapse.

PMID- 9582995
TI  - [Resolution of the Second (XVIII) of the All-Russian Pirogov Congress of
      Physicians].

PMID- 9582996
TI  - A.E. Bennett Research Award. Toward a neurodevelopmental model of of obsessive-
      compulsive disorder.
AB  - BACKGROUND: Neurobiological models for obsessive-compulsive disorder (OCD) have
      consistently implicated ventral prefrontal cortical and striatal circuits in the
      pathophysiology of this disorder, but typically have not utilized a developmental
      framework for conceptualizing the illness. METHODS: We describe an integrated
      series of neurobiologic studies aimed at testing the hypothesis that
      neurodevelopmental abnormalities of ventral prefrontal-striatal circuits may be
      involved in and contribute to the etiology and presentation of the illness.
      RESULTS: Using studies of oculomotor physiology, we have identified a selective
      deficit in neurobehavioral response suppression in OCD that may be related to
      failures in the developmental maturation of frontostriatal circuitry. Magnetic
      resonance imaging studies showed that treatment-naive pediatric OCD patients had
      significant volumetric abnormalities in ventral prefrontal cortical and striatal
      regions but no abnormalities in dorsolateral prefrontal cortex. Severity of OCD
      symptoms but not illness duration was related to ventral prefrontal cortical and
      striatal volumes. CONCLUSIONS: Critical neurodevelopmental changes in ventral
      prefrontal-striatal circuitry may be associated with the initial presentation of
      OCD, and a developmentally mediated network dysplasia may underlie OCD. Such
      dysplasia in ventral prefrontal cortical circuits could manifest clinically by
      disrupting brain functions that mediate ongoing purposive behaviors.

PMID- 9582997
TI  - Regionally specific neuronal pathology in untreated patients with schizophrenia:
      a proton magnetic resonance spectroscopic imaging study.
AB  - BACKGROUND: Proton magnetic resonance spectroscopic imaging (1H-MRSI) studies
      have reported reductions of N-acetyl aspartate (NAA), a marker of neuronal
      integrity, in the hippocampal region (HIPPO) and dorsolateral prefrontal cortex
      (DLPFC) of pharmacologically treated patients with schizophrenia. The purpose of
      the present study was twofold: to exclude drug treatment as a source of the
      previous findings and to examine NAA relative concentrations in a unique sample
      of chronically untreated patients. METHODS: We studied 12 medication-free
      patients, 5 of whom were "drug naive" and symptomatic for a mean of 12 years, and
      12 control subjects. Ratios of areas under the metabolite peaks of the proton
      spectra were determined [i.e., NAA/creatine (CRE), NAA/choline (CHO), CHO/CRE]
      for multiple cortical and subcortical regions. Hippocampal formation and frontal
      lobe volumes were also measured to test for correlations with 1H-MRSI data.
      RESULTS: Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in
      HIPPO and DLPFC. There were no significant changes in CHO/CRE or in NAA ratios in
      any other area sampled. No significant correlation was found between metabolite
      ratios, length of illness, and volumes of the hippocampal region and frontal
      lobe. Mean ratios and effect sizes were not different in chronically ill but
      still medication-naive patients in comparison with subacute patients and
      previously studied chronic patients receiving medications. CONCLUSIONS: Bilateral
      reductions of NAA ratios in HIPPO and DLPFC are reliable findings. The findings
      implicate a relatively localized pattern of neurochemical pathology that does not
      appear to change with prolonged illness whether medicated or unmedicated.

PMID- 9582998
TI  - Volumetric evaluation of the thalamus in schizophrenic male patients using
      magnetic resonance imaging.
AB  - BACKGROUND: The thalamus, an important subcortical brain region connecting limbic
      and prefrontal cortices, has a significant role in sensory and cortical
      processing. Although inconsistently, previous studies have demonstrated
      neuroanatomical abnormalities in the thalamus of schizophrenic patients. METHODS:
      This structural magnetic resonance imaging study, based on segmentation of
      contiguous coronal 1.5-mm images, compared thalamic brain volumes of 15 chronic,
      male schizophrenic patients with 15 normal controls matched on age, sex,
      handedness, and parental socioeconomic status. RESULTS: There were no significant
      differences between patients and controls in thalamic volumes, right or left,
      adjusted for total brain volume; however, there were significantly different
      correlations of thalamic volumes with prefrontal white matter and lateral
      ventricles among patients, but not among controls. Thalamic volumes among
      patients were also significantly correlated with bizarre behavior,
      hallucinations, and thought disorder. CONCLUSIONS: Findings suggest that
      connectivity between thalamic nuclei and prefrontal cortical areas are abnormal
      in chronic male schizophrenic patients. In addition, ventricular enlargement may
      be, in part, due to subtle reduction in thalamic volume and/or in volume of
      thalamocortical and corticothalamic fibers secondary to thalamic abnormalities.
      Finally, correlations with positive symptomatology underscore the role of the
      thalamus in gating or filtering of sensory information and coordination of
      cortical processing.

PMID- 9582999
TI  - D2 dopamine receptor up-regulation, treatment response, neurological soft signs,
      and extrapyramidal side effects in schizophrenia: a follow-up study with 123I
      iodobenzamide single photon emission computed tomography in the drug-naive state
      and after neuroleptic treatment.
AB  - BACKGROUND: Animal and postmortem studies indicate that neuroleptic therapy may
      induce D2 dopamine receptor up-regulation in the basal ganglia. METHODS: To
      address this phenomenon in a clinical study, we investigated the D2 dopamine
      receptor binding in 15 DSM-III-R schizophrenics in the drug-naive state and 3
      days after completion of a standardized neuroleptic therapy (benperidol 12-16
      mg/day, for 25 days) using single photon emission computed tomography (SPECT).
      SPECT scans were obtained 2 hours after intravenous injection of 185 MBq 123I
      iodobenzamide. For analysis, basal ganglia to frontal cortex (BG/FC) ratios were
      calculated and the patient sample was subgrouped into patients with a favorable
      versus a poor treatment response. RESULTS: Neuroleptic treatment led to decreased
      BG/FC ratios in patients with a favorable response, but increased ratios in the
      poor responders (df = 1, F = 4.1, p = .06). Changes of BG/FC ratios were
      significantly correlated with extrapyramidal side effects but not with
      neurological soft signs. CONCLUSIONS: Our findings suggest that neuroleptic
      therapy may induce D2 dopamine receptor up-regulation in a subgroup of patients
      characterized by poor treatment response and pronounced extrapyramidal side
      effects.

PMID- 9583000
TI  - Cognitive frontal lobe dysfunction in obsessive-compulsive disorder.
AB  - BACKGROUND: There is evidence that dysfunction within associative frontostriatal
      circuits represents a feature of obsessive-compulsive disorder (OCD). Previous
      neuropsychologic studies have yielded diverging results, which may in part be
      explained by differences in the selection of subjects and methods. The present
      study focused on the question of cognitive frontal lobe performance in OCD.
      METHODS: Twenty-nine unmedicated OCD patients were compared to a double-size
      control group of normal subjects matched individually for age, sex, and
      intelligence. A series of 12 neuropsychologic tests was applied, most of which
      are thought to be sensitive to different aspects of cognitive frontal lobe
      function. RESULTS: OCD patients were unimpaired at tests of abstraction, problem
      solving, set-shifting, response inhibition, active memory search, and choice
      reaction speed. Deficits of approximately one standard deviation were observed at
      timed tests of verbal and nonverbal fluency, attentional processing, and weight
      sorting. CONCLUSIONS: OCD patients exhibited selective deficits in tasks
      involving controlled attentional processing and self-guided, spontaneous
      behavior. We discuss a link between this neuropsychologic profile and
      dysfunctioning within the anterior cingulate, but not the dorsolateral prefrontal
      circuit.

PMID- 9583001
TI  - Elevated plasma lipid peroxides at the onset of nonaffective psychosis.
AB  - BACKGROUND: Impaired antioxidant defense and increased lipid peroxidation has
      been reported in chronic schizophrenic patients. Recently, we have reported an
      impaired antioxidant defense in never medicated first-episode schizophrenic and
      schizophreniform patients. We report now a concomitant increase in plasma lipid
      peroxides. METHODS: The plasma lipid peroxides [thiobarbituric acid reactive
      substances (TBARS)] were analyzed by chemical and high performance liquid
      chromatography procedures in 26 patients admitted for a first episode of
      schizophrenic (N = 17) or schizophreniform psychosis (N = 9) and 16 normal
      control subjects. The patients had a duration of 4.5 days (SD 2.8) of psychosis
      at the time of the study. RESULTS: Plasma TBARS levels were significantly higher
      in the patients than in normal controls (P < .002). TBARS levels were above the
      normal range in 16 of the 26 patients. Higher TBARS levels were associated with a
      greater severity of negative symptoms and lower red blood cell activity of the
      glutathione peroxidase. CONCLUSIONS: The findings indicate ongoing oxidative
      injury at the very onset of psychosis. If valid, this would indicate the need for
      adjunctive antioxidant treatment from the beginning of the course of nonaffective
      psychoses. This might prevent a deteriorating course and development of the
      deficit syndrome.

PMID- 9583002
TI  - Further studies of elevated cerebrospinal fluid neuronal cell adhesion molecule
      in schizophrenia.
AB  - BACKGROUND: The purposes of the present study were to attempt to replicate a
      previous finding of increased cerebrospinal fluid (CSF) neuronal cell adhesion
      molecule (N-CAM) in schizophrenia, and to assess whether the increases could be
      related to medication, clinical state effects, or brain structural measures.
      METHODS: CSF N-CAM was measured by the Western blot technique in 45 DSM-III-R
      diagnosed male schizophrenic patients both on and off haloperidol treatment and
      in 20 healthy male control subjects. RESULTS: CSF N-CAM was significantly
      increased in schizophrenic patients, with no overlap in the ranges, when compared
      to controls. There were no significant effects of medication or exacerbation on
      CSF N-CAM. No associations with measures of brain structure were found.
      CONCLUSIONS: Because N-CAM levels were not shown to be different on and off
      treatment or in exacerbated versus nonexacerbated patients, the higher levels
      seen in schizophrenic patients may be inherent to the disorder and possibly
      related to neurodevelopment.

PMID- 9583003
TI  - Mortality hazard associated with prescription hypnotics.
AB  - BACKGROUND: The American Cancer Society's Cancer Prevention Study II was a large
      survey designed primarily to examine cancer risks such as cigarette smoking. From
      the same survey and methods, data on usage of "prescription sleeping pills" in
      1982 were examined. METHODS: Standardized mortality ratios were computed. Because
      sleeping pill use could be a proxy for other risk factors, cox proportional
      hazards models were computed to control for possible confounding factors as
      extensively as the data permitted. RESULTS: Men and women who reported taking
      prescription sleeping pills 30+ times in the past month had standardized
      mortality ratios of 3.18 and 2.82, respectively; controlling for 10-year age
      groups (p < 0.001). The standardized mortality ratios for usage 1-29 times/month
      were 1.8 and 1.48, respectively (p < 0.001). In proportional hazards models that
      controlled for 30 other risk factors and comorbidities simultaneously, the excess
      mortality risk associated with usage 30+ times per month remained significant,
      but hazard ratios were reduced to 1.35 for men and 1.22 for women. CONCLUSIONS:
      Use of hypnotics was associated with excess mortality. This methodology could not
      determine if hypnotic compounds caused the risks associated with their use, nor
      could the risks of individual compounds be determined. Since millions of
      Americans are currently taking hypnotics, long-term controlled trials are
      urgently needed to further guide both patients and physicians.

PMID- 9583004
TI  - Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a
      prospective study.
AB  - BACKGROUND: Though among the most abundant human steroid hormones, the
      physiologic role of dehydroepiandrosterone and its sulfate (DHEAS) is not known.
      Our goal was to determine if DHEAS is associated with cognition and mood in older
      women, and if baseline DHEAS levels are predictive of cognitive decline. METHODS:
      In a prospective cohort, we studied 394 randomly selected community-dwelling
      women, aged 65 years or older, currently enrolled in the Study of Osteoporotic
      Fractures. Subjects were administered a modified Mini-Mental State Exam, Trials
      B, Digit Symbol, and the Geriatric Depression Scale-Shortened (GDSS), at study
      onset and 4-6 years later. Serum was obtained at study initiation for DHEAS
      analysis. RESULTS: DHEAS levels declined with age, as expected. There was no
      consistent association of DHEAS quartile or log DHEAS with any of the four
      outcomes, even after multivariate adjustment. Change in cognitive performance
      overtime was not associated with DHEAS levels. Analysis of the 32 women without
      any detectable DHEAS compared to those with detectable levels revealed higher
      measures on the GDSS (mean score 3.4 +/- 3.6 compared with 1.6 +/- 2.3, p = .028)
      and a higher percentage with depression (21.7% compared with 4.6%, p = .001).
      CONCLUSIONS: Serum DHEAS is not a sensitive predictor of cognitive performance or
      decline on a selected neuropsychological battery in elderly community women;
      however, nondetectable levels may be associated with depression.

PMID- 9583005
TI  - Decreased interleukin-2 production in Korean schizophrenic patients.
AB  - BACKGROUND: It has been postulated that autoimmune process may play a role in the
      pathogenesis of symptoms in some schizophrenic patients. Findings of altered
      interleukin (IL) regulation have been regarded as additional proof that
      schizophrenia has an autoimmunological background. METHODS: Sixteen patients who
      fulfilled DSM-IV criteria for schizophrenia and who were drug free for at least
      six months and the same number of age- and sex-matched controls were recruited.
      The severity of symptoms in schizophrenia was assessed by BPRS.
      Phytohemagglutinin (PHA)-stimulated production and serum level of IL-1 beta, IL
      2, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      There was a significant decrease of IL-2 production (p < .01) in schizophrenic
      patients and a significant increase of IL-2 serum level (p < .01). No significant
      difference of IL-1 beta and IL-6 was found. Some patients and controls had
      measurable serum level of IL-1 beta and IL-6. No significant correlation between
      production and serum level of IL-1 beta, -2, -6 and age, duration of illness, and
      BPRS score in schizophrenics was found. CONCLUSIONS: This is the first study to
      describe a decrease of IL-2 production and increase of IL-2 serum level in non
      Caucasian schizophrenic patients. These findings are further evidence that
      autoimmune process is present, regardless of ethnic origin, in some schizophrenic
      patients.

PMID- 9583006
TI  - Reflux strictures of the esophagus.
AB  - Gastroesophageal reflux disease (GERD) is the most common cause of esophageal
      strictures, accounting for approximately 70% of all cases. Reflux strictures of
      the esophagus are serious complications of GERD and are associated with a high
      relapse rate. Goals of long-term management include the relief of dysphagia,
      prevention of stricture recurrence, and avoidance of complications with safe,
      cost-effective therapy. Despite recent advances in knowledge about GERD, reflux
      stricture still remains a relatively common and challenging clinical problem.

PMID- 9583007
TI  - Esophageal strictures. A radiologic approach to diagnosis and management.
AB  - Strictures of the esophagus represent persistent luminal narrowing following an
      inflammatory insult to mural tissues or a manifestation of malignant disease.
      Barium studies remain the cornerstone of evaluation of patients with a suspected
      stricture. The diagnostic features of the various causes of strictures are
      discussed. Balloon dilatation and stent placement, as well as other radiologic
      interventions, often have an important role in the treatment of patients with
      advanced disease. This article discusses the indications and general application
      of these procedures as well as the nature and evaluation of the associated
      complications.

PMID- 9583008
TI  - Endosonography in the assessment of esophageal stenosis.
AB  - EUS is an invaluable tool to delineate the cause of esophageal strictures. In
      primary esophageal carcinoma, EUS is the most accurate means for locoregional
      tumor staging. The addition of EUS FNA improves lymph node staging accuracy over
      EUS alone. EUS FNA can also play a role in diagnosing the cause of strictures
      associated with lymphadenopathy or metastatic tumor. In all settings, aggressive
      dilation to allow passage of the echoendoscope is associated with a substantial
      risk of perforation and should be avoided. To overcome this problem, catheter
      based and over-the-wire probes are being developed to permit EUS imaging of
      severe stenoses.

PMID- 9583009
TI  - Benign nonpeptic esophageal strictures. Diagnosis and treatment.
AB  - This article studies the causes and treatment of benign nonpeptic esophageal
      strictures. The authors also discuss various therapeutic techniques for
      esophageal strictures, including esophageal dilatation with various dilators and
      balloons. Although the goals of stricture therapy are to relieve dysphagia and
      prevent stricture reoccurrence, only the first of these goals (effective
      dilatation with bougienage or balloon dilatation) has been achieved. The
      prevention of stricture reoccurrence remains to be achieved.

PMID- 9583010
TI  - Extramucosal stenosis of the esophagus.
AB  - Extramucosal lesions of the esophagus compose a small but clinically important
      group of diagnoses presenting as stenosis. Because of their infrequency, they can
      present a diagnostic dilemma in patients with dysphagia, odynophagia, or
      radiologic abnormalities on imaging studies. Definitive management is frequently
      conservative, consisting of reassurance; definitive surgical management, however,
      may be necessary.

PMID- 9583012
TI  - Nutritional aspects of strictures.
AB  - Malnutrition is common and often undiagnosed in affected patients, especially
      those in the hospital, and is associated with impaired organ function, increased
      morbidity, and prolongation of hospital stay. It should be recognized and treated
      appropriately, because artificial nutritional support in malnourished patients
      leads to improvement in nutritional status and clinical outcome. There are
      multiple methods to provide nutrition, some by simply keeping the esophageal
      lumen patent, others by providing additional or all nutrients, including enteral
      and parenteral routes. The enteral route is preferred due to patient acceptance,
      lesser expense, and lower risk of complications. The addition of specific
      nutrients over standard diets may add benefit. Preoperative nutrition may reduce
      the risk of postoperative complications. Lastly, in the terminally ill patient,
      minimal intervention may be all that is needed to achieve the patient's comfort,
      perhaps the most important goal.

PMID- 9583011
TI  - Esophageal stenosis in children.
AB  - This article focuses on the special features of esophageal stenosis which pertain
      to children. In order to focus on stenoses intrinsic to the esophagus, esophageal
      stenosis due to extrinsic compression is excluded. While the causes of esophageal
      stenosis may be grouped as either congenital or acquired, congenital causes
      account for less than 5% of cases.

PMID- 9583013
TI  - Surgery for peptic strictures.
AB  - Benign peptic stricture of the esophagus is a complex disorder which results from
      persistent gastroesophageal reflux. Its successful management depends on an
      accurate preoperative evaluation of the stricture and the patient. Surgical
      management of peptic strictures can be quite effective in relieving the symptoms
      and halting the pathologic gastroesophageal reflux that accompanies this
      disorder. This article reviews the general principles of evaluation and surgical
      treatment of benign peptic esophageal strictures.

PMID- 9583014
TI  - An overview of the management of cancer of the esophagus.
AB  - The surgical treatment of esophageal cancer concerns a small percentage of
      patients with small Stage I or II tumors and a good performance status.
      Nonsurgical management with concurrent radiation and chemotherapy concerns a
      larger group of patients, and complete tumor responses have been observed at a
      significant rate. This applies to inoperable patients and to operable patients
      when there is a relative contraindication or when large malignant lymph nodes are
      detected at the preoperative stage. Endoscopic palliation in monotherapy should
      be restricted to the smallest possible number of patients.

PMID- 9583015
TI  - Operative treatment of malignancy.
AB  - The overall prognosis of patients afflicted with cancer of the esophagus is
      dismal and has not changed greatly over the last few decades. Improvements have
      largely been due to better perioperative care rather than new surgical
      techniques. There remain, about the optimal treatment of these patients, and
      these differences are summarized in this article. The principal elements required
      to make an appropriate surgical decision also are outlined. Until new markers for
      early detection and effective systematic therapy emerge, improvement is likely to
      occur only in subsets of patients referred early and treated in an environment
      that guarantees low operative mortality.

PMID- 9583016
TI  - Radiation and chemotherapy in the management of malignant esophageal strictures.
AB  - The management of malignant and esophageal strictures with radiation and
      chemotherapy is reviewed. There is no evidence to support the use of adjuvant
      radiation. Studies demonstrate that concurrent chemotherapy and radiation are
      superior to radiation alone. The trials of preoperative combined chemotherapy and
      radiation are discussed, and it is suggested that further studies are needed
      before such treatment could be accepted as standard therapy. The roles of
      radiation and chemotherapy in palliative management are briefly discussed, and
      some potential areas for further study are proposed.

PMID- 9583018
TI  - Malignant strictures. Thermal treatment.
AB  - Malignant stenoses can occur in any part of the gastrointestinal tract.
      Endoscopic treatment options are available, however, only for the rectosigmoid
      area, the esophagus, and the esophagocardial transition. Strictures in the
      esophageal region represent the quantitatively predominant type of stenoses
      encountered in everyday endoscopy.

PMID- 9583020
TI  - [Plastic surgery of protruding ears].

PMID- 9583019
TI  - The use of stents in the management of malignant esophageal strictures.
AB  - The majority of patients with intrinsic or extrinsic obstructing esophageal
      malignancies are not treatable for cure because of an advanced tumor stage at the
      time of diagnosis or a recurrence after primary curative therapy. Palliative
      treatment is mainly directed at relieving dysphagia, which is a frequent cause of
      patient distress and malnutrition. The approach should be rapidly effective,
      safe, and well tolerated; the period of hospitalization should be limited in view
      of a life expectancy of only a few months.

PMID- 9583021
TI  - [Principles of cleft nose correction].

PMID- 9583017
TI  - Nonthermal ablation of malignant esophageal strictures. Photodynamic therapy,
      endoscopic intratumoral injections, and novel modalities.
AB  - Several novel nonthermal ablative modalities for the palliation of malignant
      esophageal stenoses have been developed over the past decade. In this article,
      the authors review techniques and clinical experience with photodynamic therapy
      as well as the intratumoral injection of alcohol, cytotoxins, and
      immunomodulators.

PMID- 9583022
TI  - [Cerebrospinal rhinorrhea--cerebrospinal otorrhea].

PMID- 9583023
TI  - [Education in surgery of the middle ear and temporal bone].

PMID- 9583024
TI  - [Biomechanics of the reconstructed ear ossicular chain].

PMID- 9583025
TI  - [Cerebrospinal rhinorrhea and cerebrospinal otorrhea].

PMID- 9583026
TI  - [Value of Schuller conventional roentgen diagnosis and computerized tomography of
      the temporal bone in preoperative diagnosis of the Tubingen implantable cochlear
      amplifier].
AB  - Recently, the transducer and microphone of a cochlea amplifier implant (CAI) for
      the treatment of sensorineural cochlear hearing loss have been developed further
      for implantation into the mastoid cavity. At present, the University of Tuebingen
      implantable cochlea amplifier consists of an implantable microphone and an
      implantable piezoelectric transducer. It has been implanted into the first
      patients. Successful future application of this new implant depends on the
      suitable fit of the CAI within a patient's mastoid cavity. Using conventional X
      ray and CT scans, we analyzed 50 cadaver specimens of the temporal bone before
      total mastoidectomy. After total mastoidectomy, the volume of the mastoid cavity
      was measured using CT scans and water volume determination. Finally, the CAI was
      implanted into those temporal bones that were large enough to house it. Our
      results demonstrate that the degree of pneumatization in the conventional
      Schuller X-ray is already a good parameter for preoperative evaluation.

PMID- 9583027
TI  - [Argon plasma coagulation in treatment of hereditary hemorrhagic telangiectasia
      of the nasal mucosa].
AB  - Patients with hereditary hemorrhagic telangiectasia (M. Osler-Rendu-Weber
      disease) often suffer from recurrent epistaxis that poses considerable
      therapeutic problems. Dermoplasty, electrocoagulation, laser coagulation, iridium
      brachytherapy and systemic administration of estrogens have been proposed for
      treatment. Until recently argon plasma coagulation (APC) was not used in ENT
      surgery, but theoretical considerations render APC a promising therapeutic method
      for controlling nasal bleeding. Coagulation of tissue is limited to 1-2 mm of
      penetration and therefore risk of damage to adjacent tissue is low. Effects are
      best in tissues with high electric conductivity, especially for coagulating
      bleeding lesions and blood vessels. We have now treated four patients with
      telangiectasias in the nasal mucosa who had long histories of treatment for
      epistaxis. The patients were satisfied with the postoperative results and the
      frequency and intensity of bleeding were significantly reduced. Initial clinical
      experiences show that APC is a useful alternative for the treatment of bleeding
      telangiectasias in the nasal mucosa.

PMID- 9583028
TI  - [Retrospective analysis of selected tumor markers (p53, PCNA, Ki67; DNA ploidy)
      and ultrastructure in patients with larynx carcinomas].
AB  - A comparison was made of the staining intensities of selected immunohistochemical
      proliferating antigens (p53, PCNA, Ki67), DNA flow-cytometry and ultrastructures
      of neoplastic cells from 120 cases of laryngeal cancers. Clinically very advanced
      tumors were in the majority (T3, 43%; T4, 18%). A 5-grade scale was adopted to
      evaluate the level of immunohistochemical staining of the carcinoma cell nuclei.
      Positive staining was obtained in 70% for p53, 57% for Ki67 and 80% for PCNA.
      Sixty-two percent of the cases were DNA-diploid and 38% DNA-aneuploid. The DNA
      diploid carcinomas were accompanied by enlargement of the cell nuclei,
      preservation of wide margins of nuclear heterochromatin, enlargements of the
      nuclear areas and increases in the number of nuclei. In the aneuploid-polyploid
      cancers the nuclei had a substantial polymorphism, with large cleaved nuclei
      showing significant variations in size and having a nuclear envelope. A frequent
      finding was euchromatization of chromatin. Dense chromatin appeared in the form
      of small clumps spread over the whole area of these irregular nuclei. Enlargement
      and activation of nucleoli were found. There was a positive (chi-square)
      correlation between T- and N-stage and immunohistochemical staining. There was
      also a positive correlation in staining intensity between p53, Ki67 and PCNA
      markers and strong correlation between these markers for proliferative activity
      and the degree of aggressiveness of a tumor.

PMID- 9583029
TI  - [Measuring vibration properties of middle ear implants with the mechanical middle
      ear model. Initial results].
AB  - With the aid of a mechanical middle ear model (MMM) the sound transmission
      properties of different middle ear implants were investigated. Input of the MMM
      involved a broad-band signal from 100 to 5000 Hz that was supplied by a
      miniaturized loudspeaker. Displacement of an artificial stapes footplate was
      measured by a fiberoptic probe. The transfer functions of four different total
      ossicular replacement prostheses (TORPs) of different materials and shapes were
      compared. Three of the devices revealed similar transfer functions which
      corresponded to the typical curve of the normal middle ear. One of the prostheses
      demonstrated a high-frequency deterioration of approximately 5 dB. This effect
      was explained by a 3- to 6-times higher mass of the implant when compared to the
      others. Altogether, the weight of the prosthesis seems to have the most marked
      impact on sound transmission to the inner ear, whereas stiffness of the implant
      itself is less crucial as long as it can be regarded as a rigid body.

PMID- 9583030
TI  - [Practice surgery on the artificial temporal bone. Development of temporal bone
      facsimiles with stereolithography].
AB  - Learning microsurgery of the middle ear requires preparations of temporal bones.
      Ethical and moral restrictions in obtaining specimens make training and research
      with temporal bone preparations increasingly more difficult. Due to the complex
      structure of the temporal bone with its communicating cavities, the manufacture
      of facsimiles up to now has been impossible. Rapid prototyping techniques must be
      able to produce identical objects from an original one. By using CT scans of
      temporal bones from anatomic preparations and patients we have been able to
      reconstruct 3D pictures on a CAD workstation. We are now able to incorporate data
      in a stereolithographic system to create an anatomic facsimile of the temporal
      bone. It is possible to produce a considerable number of these facsimiles from
      the same real object. With this method we can produce models of human structure
      for medical teaching, training and research. Our artificial preparations of
      temporal bones correspond to both the material characteristics and anatomic
      details of human structures, allowing various surgical exercises to be carried
      out.

PMID- 9583031
TI  - [Etiology of moderate and profound deafness in childhood].
AB  - The present study sought to determine the etiology of bilateral profound hearing
      losses in children living in Germany. Additionally, a comparison with the data of
      previous investigations in the available literature was used to update causes now
      known through medical progress. PATIENTS AND METHODS: The medical charts of 314
      profoundly hearing-impaired pupils at schools for the deaf in Cologne, Germany,
      were reviewed. All available data on possible etiological factors were collected.
      In addition, the families of these children were interviewed using a standardized
      questionnaire. RESULTS: Sixty children were found to have bilateral sensorineural
      hearing losses averaging 30 to 60dBHL within the frequency ranges of 500-2000 HZ,
      while 254 had bilateral hearing impairments of 60 dBHL or greater. The etiology
      of the hearing disorder could be determined in 218 of the children. Eighty-two
      children suffered from hereditary deafness and 136 from acquired hearing losses.
      The etiology could not be determined in 96 children. Hereditary causes included
      34 children with mendelian autosomal dominant losses, 46 with autosomal recessive
      losses and two children with genetic but non-mendelian causes. Immigrants to
      Germany (mostly from Turkey and the former Soviet Union) were found significantly
      more frequently among the students of these schools, than among the total
      population of the Cologne area. In this group of students, autosomal recessive
      deafness was particularly common as compared to the overall native population.
      Acquired hearing disorders were broken down into three subgroups: prenatal,
      perinatal and postnatal disorders. A prenatal etiology was considered in 32
      children, 21 of whom had known congenital rubella infection. This entity was
      significantly less common among younger children. A perinatal etiology was
      considered in 60 children. Causative factors were birth asphyxia, apnea and/or
      hyperbilirubinemia. Forty-four children had deafness attributed to postnatal
      causes, with bacterial meningitis (n = 31) being the most important single
      factor. The findings reported indicate changing trends for causes of hearing loss
      in children with severe hearing impairment in Germany.

PMID- 9583032
TI  - [Compulsive swallowing of foreign bodies. Esophageal foreign body].

PMID- 9583033
TI  - [Exophytic papillomatous space-occupying lesions of the larynx as a rare
      manifestation of candidiasis. Diagnostic and therapeutic consequences].
AB  - Laryngeal candidiasis is very rare in the absence of other more proximal diseases
      in the aerodigestive tract. The lesion shows pseudoepitheliomatous hyperplasia or
      acanthosis and, given its rarity, may be confused with cancer. In the present
      paper we report on a 56-year-old male patient who presented with hoarseness.
      Physical examination of the larynx revealed a hyperplastic lesion involving both
      vocal cords. The clinical aspect and the risk factor profile of the patient (ten
      bottles of beer and 40 cigarettes per day) generated the clinical diagnosis of
      laryngeal cancer. A biopsy was taken. The histopathological examination of the
      specimen excluded a squamous cell carcinoma; however, it could not provide a
      clear diagnosis. Laryngeal papillomatosis and tuberculosis, which had been
      suspected, could be excluded. As the lesion progressed, further biopsies led to
      the diagnosis of candidiasis. Systemic antimycotic treatment with fluconazol and
      amphotericin caused a complete remission.

PMID- 9583034
TI  - [Epidural hematoma with secondary middle ear involvement. A rare differential
      diagnosis of otogenic brain abscess].
AB  - Processes in the middle ear can occasionally lead to clinical disorders extending
      beyond the anatomic boundaries of the area of the mastoid process. In contrast to
      this, pathological processes of the areas adjoining the middle ear might also
      lead to secondary involvement of the tympanic area. The report describes an
      initially asymptomatic epidural hematoma, which secondarily led to involvement of
      the middle ear. In general, such cases affecting the middle ear will produce
      symptoms usually interpreted as primary middle ear pathology. This association
      shows which disorders must be considered, the differential diagnosis and methods
      of therapy.

PMID- 9583035
TI  - [Spontaneous, unilateral necrosis of the tongue. Temporal arteritis].

PMID- 9583036
TI  - ["Of snakes and crocodiles". Central side effects caused by nose drops].

PMID- 9583037
TI  - [Therapeutic use of botulinum toxin in otorhinolaryngology. 1: Treatment of
      movement disorders of mimetic muscles].

PMID- 9583038
TI  - [Allergic rhinitis. Antihistamine with dual effect also reduces obstruction].

PMID- 9583041
TI  - [Indications for axillary node dissection in breast cancers].
AB  - Axillary lymph node dissection is in theory of both therapeutic and prognostic
      benefit for patients with breast cancer. For several authors, its therapeutic
      function, which consists in surgical dissection of potentially metastatic nodes,
      may be assured effectively by radiotherapy, but results of different comparative
      studies are contradictive. However, axillary dissection should be eliminated for
      small tumors (< 5 mm) because of the low yield of positive nodes (< 3%). Even if
      new histologic prognosticators are currently in evaluation, axillary node
      stagging is the single most important prognostic variable, and determines the
      indication for chemotherapy for premenopausal patients. Morbidity remains high,
      even if rarely severe, and new technologies are studied to try to locate the
      first node draining the tumor, in order to pick it out electively for histologic
      examination.

PMID- 9583042
TI  - [Follow-up of women treated for breast cancer. State of the art].
AB  - The intensive follow up of breast cancer patients is not safer than a minimalist
      policy for breast cancer surveillance. The survival rate is not modified by the
      use of expensive exams. Follow up program are stressful, delay the patient
      rehabilitation and are useless because in 75% of cases the patient discovered the
      relapse by herself. A good clinical examination, including gynecological
      examination and a mammography are sufficient for a good follow up practice. The
      guide lines for the follow up of breast cancer patients include self examination
      of the breast monthly, clinical examination twice a year and an annual
      mammography during five years and an annual clinical examination and a
      mammography after. The radio therapist, the surgical or medical oncologist should
      be involved with the general practitioner for this follow up.

PMID- 9583040
TI  - [It's been one hundred years: professor Stephane Tarnier (1828-1897)].

PMID- 9583043
TI  - [Triploidies].
AB  - Triploidies are pregnancies that show a 69 chromosome karyotype. This chromosomal
      abnormality gives rise to early abortion in most cases. Triploid pregnancies,
      after the first three months, become molar pregnancies (molar changes inside the
      placenta with identifiable embryonic structures and a preeclampsia) or non molar
      pregnancies (isolated intauterin growth retardation). Several possibilities
      concerning the origin of the additional set of chromosomes exist: dispermy (the
      most common), diandry and digyny. The maternal and fetal clinical manifestations
      of this chromosomal abnormality are very diverse, which explains the difficulty
      of finding and recognizing this pathology. Mac Fadden's classification does not
      explain all the phenotypic triploid physiopathology. Formal diagnosis of
      triploidy depends on the fetal karyotype. The better the maternal prognosis is,
      the worst the fetal prognosis is. Postnatal life expectancy is not more than a
      few weeks. In most cases, maternal associated complications disappear with the
      molar evacuation. The risk of post molar tumor is discussed. However, good
      management of triploidy is based on an early diagnosis, before birth if that is
      possible.

PMID- 9583044
TI  - [Prenatal diagnosis of osteogenesis imperfecta. Two cases].
AB  - We report two cases of prenatal diagnosis of osteogenesis imperfecta (type S of
      Marotaux), diagnosed at 23 and 24 weeks of gestation, revealed by of an
      ultrasound scan which noted an abnormal femoral incurvation. The problem of
      differential diagnosis with other diseases causing femoral incurvation (notably
      campomelic dysplasia) is difficult, especially at early stage. This question is
      debated here. The interest to associate ultrasound scan and uterine contents
      radiography is so demonstrated.

PMID- 9583045
TI  - [Anatomical study of Cooper's ligament. Value in the surgical cure of urinary
      incontinence in women].
AB  - The objective of the study was to measure Cooper's ligament thickness in the
      middle and at 1, 2, 3, 4 cm and to find the best place to fix the stitches of
      colposuspension. This study was performed on fresh cadavers. Sixteen Cooper's
      ligaments were studied (8 women, mean age 78 +/- 6 years). The length, the width
      and thickness of Cooper's ligament at 0, 1, 2, 3, 4 cm from the middle were
      measured. The limits of Cooper's ligament are indefinite. This ligament is
      significantly thicker (p < 0.01) in the middle and at 4 cm from the middle (2.2
      +/- 0.4 mm) than 1 cm (1.4 +/- 0.5), 2 cm (1.4 +/- 0.5 mm) and at 3 cm (1.9 +/-
      0.3 mm) from the middle. Cooper's ligament is used to fix the stitches for
      colposuspension derived from Burch colposuspension (non-incision percutaneous
      colposuspension to Cooper's ligament, laparoscopic colposuspension...) and
      sometime help to fix meshes in frondes procedures and the vagina in the Bologna
      procedure. This study showed the best point to fix the stitches (by its
      thickness) for colposuspension on this ligament at 4 cm from the middle (the
      fixation at the origin exposing to periostitis).

PMID- 9583046
TI  - [Total hysterectomy for benign pathologies. Laparoscopic surgery does not seem to
      increase the risk of complications].
AB  - OBJECTIVE: To assess the risk of complications of total laparoscopic hysterectomy
      (TLH). SETTING: University Hospital, Surgical Gynecological team. DESIGN:
      Retrospective study of 313 patients. For all the patients a total laparoscopic
      hysterectomy was performed. Every part of the operation was carried out via
      laparoscopy, from the adnexal phase (conservative or radical) to the colpotomy.
      All hemostasis was carried out by electrosurgery (bipolar coagulation). All the
      instruments are reusable. RESULTS: The rate of conversion to laparotomy was 6.7%
      (21 patients). For the patients who underwent a TLH (292 cases; 92.3%) the
      overall complication rate was 9.95% (29 patients). The rate of patients presented
      a complication which required a further operation was 1.4% (4 patients). The rate
      of patients presented a complication which required a re-hospitalization was 2.0%
      (6 patients). The rate of major urinary injury was 2.5% (6 cases): bladder injury
      (4 patients; 1.35%); vesico-vaginal fistula (1 case; 0.35%); ureteral
      complication (1 case; 0.35%). The rate of postoperative febrile morbidity was
      5.8% (17 patients). CONCLUSIONS: These encouraging results mean that, provided
      the surgeons are experienced in laparoscopic surgery, total laparoscopic
      hysterectomy technique would appear not to have a higher rate of complications
      than hysterectomy via laparotomy or the vaginal route.

PMID- 9583047
TI  - [What does the cesarean rate mean in France/].
AB  - For more than twenty-five years, the cesarean rate in France, as in other
      developed countries, has continued to increase, and in 1995 was 15.9%. Cesareans
      are now taken for granted by the general public, who are usually unaware of their
      consequences for maternal mortality and morbidity and continue to consider this
      form of delivery as the safest for the new born child. Yet it has been clearly
      demonstrated that cesarean deliveries are associated with higher rates of
      maternal and perinatal morbidity than vaginal deliveries and that they increase
      maternal mortality by a factor of from 5 to 7. From an economic standpoint,
      cesareans are between two and three times more expensive than vaginal deliveries.
      The two main indicators which account for the increase in cesareans are
      cicatricial uterus and dystocia. These are indicators in which individual
      practitioners' normal practice and the fear of medical malpractice suits play a
      clear role. There appears to be a particular correlation between the proportion
      of cesareans and obstetricians' insurance premiums, obstetricians' own assessment
      of the risk of malpractice suits and the number of complaints lodged against
      hospitals or individual doctors. Cesareans performed on grounds of fetal
      suffering or breech deliveries represent a diminishing proportion of the total.
      The use of scalp pH and radiopelvimetry have made it possible to restrict the
      number of cesareans based on these indicators. Other factors play a role in this
      increase, such as parity, education level, type of maternity insurance, whether
      the hospital is private or public, whether or not there is a neonatal
      resuscitation unit, the size of the city and the obstetrician's experience and
      type of training. The time and day or delivery have also been shown to be
      relevant factors. For obstetricians themselves, the higher fees earned from
      cesareans do not appear to be important. Of more relevance is the opportunity
      they offer doctors to organise their schedule and save time. Among the various
      methods proposed for reducing the cesarean rate, a strict definition of and
      respect for the indications for a cesarean, involving comparisons between
      establishments and between practitioners, have been shown to be effective. To
      allow such figures to be compiled, France should therefore produce for each
      confinement a standard record containing the different perinatal data, as is
      already the case in numerous other countries.

PMID- 9583048
TI  - [Premature delivery. Epidemiology and prognosis at the Dakar University Hospital
      Center].
AB  - A prospective study included 131 premature births registered from January to
      December 1996 giving a rate of 28 per 1,000 deliveries. The epidemiological
      profile was one of a primiparous woman, mean age 25 years, admitted in a clinical
      situation of irreversible premature birth (91.6%). The prematurely born infant
      was hypotrophic in 48.8% of the cases with term less than or equal to 32 weeks.
      Vaginal delivery was achieved in most cases. Risk factors identified were: poor
      prenatal care (no prenatal check-up in 25%) and obstetrical factors (29.8%). The
      neonatal outcome included neonatal suffering (64.7%) and high mortality (30.7%).
      Care of premature infants is relatively costly with a mean daily cost of $US 30
      per day besides the cost of laboratory tests and personnel costs.

PMID- 9583049
TI  - [Value of postoperative urodynamic assessment for long-term urinary function
      results after treatment of genital prolapse. 103 examinations after treatment of
      genital prolapse].
AB  - OBJECTIVE: To evaluate the predictive value of postoperative urodynamic
      assessment on the apparition or the resurgence of genuine stress incontinence
      after a surgical procedure for genitourinary prolapse. SUBJECTS: 103 patients
      operated on for prolapse, with or without an associated surgical procedure for
      genuine stress incontinence. A review of the results of the urodynamic assessment
      carried out during the early post operative period was effected. RESULTS: 77.7%
      of the patients had an associated procedure for stress incontinence during
      surgery for prolapse. An urodynamic abnormality such as intrinsic sphincter
      deficiency and/or transmission ratio default was noted in 83.3% of the women who
      demonstrated incontinency during postoperative assessment, and in 76.7% of the
      patients without any problem of continence. During long term follow up, only
      41.7% of the women who were incontinent shared intrinsic sphincter deficiency,
      and an abnormal cytometric parameter was noted in 74.4% of continent patients.
      86% of the patients who were incontinent in the early postoperative period will
      remain so, whatever the result of the cystometric evaluation. CONCLUSION: Our
      results show that there is no correlation between the various cystometric
      parameters evaluated during the postoperative period, and the symptoms described
      by the patients. The absence of abnormal urodynamic assessment cannot
      consistently predict normal bladder function. Only postoperative symptoms can be
      considered to be predictive of a satisfactory surgical cure.

PMID- 9583050
TI  - [Evaluation of combination RU 486-laminaria tents-misoprostol-peridural
      anesthesia in second and third trimester induced abortions].
AB  - OBJECTIVE: To evaluate a new protocol for mid and third trimester medical
      termination of pregnancy using RU 486-misoprostol-epidural analgesia. DESIGN AND
      SETTING: Monocentric, prospective and descriptive study in a teaching hospital.
      MATERIALS AND METHODS: Eighty-three women undergoing legal induced abortion
      during the second and third trimester. Administration of 600 mg mifepristone 36
      hours prior to laminaria tents. 48 hours after RU 486, misoprostol was orally
      given on a 3 hours basis. Epidural analgesia was systematically performed. MAIN
      OUTCOME MEASURES: Induction-abortion interval, median dose of misoprostol,
      maternal complications, number of fetal autopsies obtained within 24 hours.
      RESULTS: The mean induction abortion interval was 3 h for multiparas and 4.45 h
      for nulliparas. The median dose of misoprostol was 800 micrograms. A uterine
      rupture on a scarred uterus occurred. The rate of fetal autopsies in cases of
      malformations within 24 hours reached 96%. CONCLUSIONS: This protocol allows a
      safe, rapid, cheap and painless late termination of pregnancy, when compared to
      other protocols.

PMID- 9583051
TI  - [Isolated peritoneal metastases from an lobular infiltrating breast carcinoma.
      Value of laparoscopy].
AB  - The authors report a case of peritoneal metastasis from an infiltrating lobular
      carcinoma of the breast. This case report enhances the frequency of this type of
      secondary location in the lobular carcinoma, with special attention to the
      diagnostic problems.

PMID- 9583052
TI  - [Intrahepatic arteriovenous fistula. Prenatal diagnosis, physiopathological study
      and neonatal management]l.
AB  - A case of arteriovenous fistula of the liver diagnosed at 30 weeks of gestation
      is reported. The etiologies of an hypoechogenic structure in the fetal liver are
      discussed showing the contribution of pulsed wave Doppler and color Doppler to
      the diagnosis. The clinical evolution towards heart failure led us to examine the
      pathophysiology of such a lesion. The prenatal management of this arteriovenous
      malformation is exposed.

PMID- 9583053
TI  - ["Legal and medical value of recording the fetal heart rate during labor"].

PMID- 9583054
TI  - Setting aside the model in family therapy.

PMID- 9583055
TI  - From rigid borderlines to fertile borderlands: reconfiguring family therapy.

PMID- 9583056
TI  - Participatory evaluation research: an introduction for family therapists.
AB  - Participatory evaluation research empowers the consumers of services to become
      leaders in evaluation and change. Participatory research methods have been used
      widely in developing countries and are consistent with family therapy's recent
      emphasis on non-hierarchical, empowering, collaborative therapies. In this paper,
      the authors present several examples of participatory evaluation methods and
      discuss their applicability to the work of family therapists.

PMID- 9583058
TI  - Life on the line: the therapeutic potentials of computer-mediated conversation.
AB  - In what ways are computer networking practices comparable to face-to-face
      therapy? With the exponential increase in computer-mediated communication and the
      increasing numbers of people joining topically based computer networks, the
      potential for grass-roots therapeutic (or antitherapeutic) interchange is greatly
      augmented. Here we report the results of research into exchanges on an electronic
      bulletin board devoted to the topic of suicide. Over an 11-month period
      participants offered each other valuable resources in terms of validation of
      experience, sympathy, acceptance, and encouragement. They also asked provocative
      questions and furnished broad-ranging advice. Hostile entries were rare. However,
      there were few communiques that parallel the change-inducing practices more
      frequent within many therapeutic settings. In effect, on-line dialogues seemed
      more sustaining than transforming. Further limits and potentials of on-line
      communication are explored.

PMID- 9583057
TI  - The process of change in couples therapy: a qualitative investigation.
AB  - Open-ended interviews with 24 couples therapy clients regarding their experience
      of the process of change revealed shifts in clusters of affect, communication,
      and cognition. Six additional contextual preconditions for change were also
      identified. The change process within couples was uniformly reported to be
      gradual.

PMID- 9583059
TI  - Not just talk, maybe some risk: the therapeutic potentials and pitfalls of
      computer-mediated conversation.

PMID- 9583060
TI  - Commitment to minority inclusion: a study of AAMFT conference program content and
      members' perceptions.
AB  - This study examined the representation of minorities and minority issues in the
      American Association for Marriage and Family Therapy. The relationship between
      AAMFT conference program content and changing social demographics from 1980 to
      1996 was explored through an ecosystemic lens, and descriptive data were elicited
      through structured interviews with clinical members. Results indicated that there
      was a significant increase in the percentage of programming devoted to minority
      issues from 1980 to 1996 while the percentage of minorities in the population
      also rose dramatically in the same period. Salient themes from the interviews are
      presented. Recommendations are made for enhancing diversity within AAMFT.

PMID- 9583061
TI  - Trainees' conjugal family experience, current intergenerational family
      relationships, and the therapeutic alliance.
AB  - This study examines the relationship between trainees' conjugal family
      experience, current intergenerational family relationships, and the client's
      perception of the therapeutic alliance. Participants were 74 first practicum
      family therapy trainees, representing two family therapy programs, and 90
      clients. Results indicated a moderately significant relationship between conjugal
      family experience and trainees' reported intergenerational intimacy with parents.
      Additionally, clients whose therapists had conjugal family experience reported a
      slightly more favorable therapeutic alliance than clients whose therapists did
      not have conjugal family experience. Additionally, trainees with conjugal family
      experience reported more current intimacy and individuation than nonconjugal
      trainees and felt less intimidated by their parents.

PMID- 9583062
TI  - A genogram with an attitude.
AB  - The approach described in this paper is predicated on the fundamental belief that
      in order to become competent and ethical practitioners, students must understand
      themselves and how they see others. They must be given tools and skills that
      facilitate examination of their own assumptions and beliefs about themselves,
      others, and how the world works. It is also essential that students examine how
      these assumptions and beliefs will influence the way they choose to conduct
      therapy. Once they are aware of their biases, they must learn to choose to
      consciously influence themselves in a way that permits their clients the largest
      room for change within the clients' own contexts of belief, understanding,
      experience, and possibility. In this paper I describe the use of the genogram as
      a tool to facilitate the process of gaining self knowledge. This tool has been
      used in a multicultural counseling course, as well as in professional development
      workshops for psychologists, mental health counselors, and marriage and family
      therapists.

PMID- 9583063
TI  - Family systems therapy after Operation Desert Storm with European-theater
      veterans.
AB  - We describe a quasi-experimental trial of time-limited family therapy with
      veterans and families of veterans who served in Europe, outside the war zone,
      during Operation Desert Storm (ODS). Family systems therapy was provided both to
      individuals and conjointly to couples or families during the acute postwar
      readjustment period. The intervention adapted strategies from structural,
      strategic, intergenerational, and behavioral family therapies in a brief
      treatment protocol for systemic stressor resolution. Veterans given family system
      therapy were able to resume functional levels of psychosocial adjustment and
      reduce the risk of long-term (chronic or delayed) psychosocial impairment. Based
      on these preliminary findings, controlled evaluation of family systems therapy
      appears warranted for individuals and families exposed to subtraumatic stressors
      such as wartime non-war-zone military deployment.

PMID- 9583064
TI  - Therapist physical attractiveness: an unexplored influence on client disclosure.
AB  - Existing research indicates that clients perceive facially attractive therapists
      as more competent, trustworthy, genuine, and effective than less attractive
      therapists. No studies exist to help explain how the therapist's attractiveness
      influences a client's self-disclosure. Participants (n = 241) were randomly
      assigned to one of eight experimental groups to test the interaction of the
      therapist's attractiveness, client's gender, the nature of presenting problem,
      and the client's comfort with disclosing in a hypothetical couple therapy
      scenario. Analysis of variance procedures established that most participants
      reported feeling more comfortable disclosing a benign (communication) problem
      than a potentially embarrassing (sexual) problem, and more comfortable disclosing
      problems to an attractive than to a less attractive female therapist. Therapists
      are encouraged to understand the power attractiveness may have in their own and
      their clients' lives.

PMID- 9583065
TI  - Pregnancy immunology and autoimmune disease.
AB  - The advent of molecular biologic techniques has resulted in the recognition of
      bidirectional traffic of cells at the maternal-fetal interface. In this light,
      and because women are preferentially affected by a wide variety of autoimmune
      diseases, the subject of pregnancy immunology is of special interest. That
      pregnancy often induces remission of rheumatoid arthritis is an intriguing
      biologic observation for which further understanding may yield insights into
      disease pathogenesis. Another important question is the effect of pregnancy on
      susceptibility to autoimmune diseases. This question is highlighted by the recent
      finding that chimeric cells can persist for many years after pregnancy
      completion. At present, the biologic significance of microchimerism from
      pregnancy is an area of research that is for the most part unexplored.

PMID- 9583066
TI  - Connective tissue disorders and pregnancy. Recommendations for prescribing.
AB  - This report summarizes experience with drugs prescribed for women with connective
      tissue disorders who either are anticipating childbearing, are pregnant or are
      breast-feeding. Principles of maintenance therapy are the same as when
      nonpregnant. Comparative trials of drugs during gestation are uncommon because of
      a lack of sufficient case numbers. It is difficult to distinguish between any
      additional risks from the medication, from any other drug and from the underlying
      disease. Symptoms of pregnancy may mimic side effects or toxic reactions to
      certain drugs. Each drug crosses the placenta, and any additional risk of
      spontaneous abortion, malformation or stillbirth is either negligible or
      unproven. Potential fetal problems with long-term intrauterine exposure to these
      drugs may include pancytopenia, immunosuppression, craniofacial abnormalities or
      restricted growth. These agents are transferred into breast milk in small
      quantities. Descriptions are provided of perinatal outcomes after in utero
      exposure to prednisone, aspirin, other nonsteroidal antiinflammatory drugs,
      antimalarials, gold salts, methotrexate, cyclophosphamide and azathioprine.

PMID- 9583067
TI  - Hypertensive disorders of pregnancy. Differentiating preeclampsia from active
      systemic lupus erythematosus.
AB  - The diagnosis of preeclampsia is made on the basis of hypertension, proteinuria
      and edema. Unfortunately, all three of these findings can be seen in the patient
      who is experiencing a flare of systemic lupus erythematosus. The management of
      these conditions is entirely different. Preeclampsia frequently results in the
      need for delivery and occasionally, especially when remote from term, can result
      in significant neonatal morbidity and mortality. Systemic lupus may be treatable
      with a variety of pharmacologic agents. It is not always possible to make the
      distinction between active lupus and preeclampsia, and occasionally the two occur
      concurrently. Nevertheless, the goal of the rheumatologist and perinatologist is
      to try to make that distinction. Physical findings and serologic markers can be
      useful in helping to distinguish between these two diagnoses. Under certain
      circumstances, delivery is indicated despite the presence of continued
      uncertainty as to the actual diagnosis.

PMID- 9583068
TI  - Systemic lupus erythematosus and pregnancy.
AB  - Systemic lupus erythematosus (SLE) may improve, exacerbate or be unchanged during
      pregnancy. The activity of SLE at the time of conception has a major influence on
      pregnancy outcome: SLE patients with quiescent disease do well, while those with
      active, uncontrollable disease have a high abortion rate. There are specific
      autoantibodies that confer a high risk of abortion (e.g., IgG antiphospholipid
      antibodies). There are others, such as anti-Ro/SSA and anti-La/SSB, which confer
      a risk for neonatal lupus that includes lupus dermatitis, congenital complete
      heart block, thrombocytopenia and cholestatic jaundice, in order of their
      relative frequencies.

PMID- 9583069
TI  - Laparoscopic retroperitoneal hysteropexy. A randomized trial.
AB  - OBJECTIVE: To assess the clinical applicability, safety and initial efficacy of a
      new laparoscopic retroperitoneal hysteropexy technique. STUDY DESIGN: A
      relatively homogeneous group of patients (N = 62) with symptomatic uterine
      retroflexion was randomly allocated to laparoscopic retroperitoneal uterine
      suspension (n = 32, group I) and diagnostic laparoscopy (n = 30, group II).
      Patients from both groups were followed for at least 24 months. The following
      clinical parameters were compared between groups I (treated) and II (untreated):
      deep dyspareunia, dysmenorrhea, sense of bladder pressure with frequent urination
      and sense of pressure in the rectum. RESULTS: Surgery was performed as an
      outpatient operation by the author. Intraoperative or postoperative complications
      were not observed in either group. A prospective, double-blind, controlled trial
      revealed that 87.5% of patients with symptomatic uterine retroflexion experienced
      relief from symptoms after the operation. Statistical analysis of the two groups
      documented that clinical symptoms improved (with P < .0001) in a statistically
      significant number of cases among patients subjected to hysteropexy. CONCLUSION:
      Laparoscopic retroperitoneal uterine suspension benefitted patients and was safe.

PMID- 9583070
TI  - Interpreting the fetal heart rate tracing. Effect of knowledge of neonatal
      outcome.
AB  - OBJECTIVE: To determine if knowledge of neonatal outcome influences
      obstetricians' retrospective interpretation of fetal heart rate monitor tracings
      and opinion on the appropriateness of obstetric care. STUDY DESIGN: Ten obstetric
      case histories that involved a critical judgment by the managing obstetrician
      were selected for this study. Each case contained a point in the patient's labor
      at which the physician made a judgment regarding route and timing of delivery. We
      assembled prenatal history, labor course, delivery, fetal heart rate tracing and
      neonatal outcome into a concise format. For each case, we created a sham case
      with identical information and monitor tracing, differing only in having an
      opposite neonatal outcome. Reviewers were recruited to participate and were
      unaware of the true intent of the study. Reviewers evaluated tracings for:
      variability, late decelerations and evidence of hypoxia, and judged whether the
      decision regarding delivery versus continued labor had been appropriate.
      Reviewers evaluated the case pairs with one month's time between the true and
      sham outcome cases. RESULTS: Thirty-six obstetricians reviewed 2 case pairs each
      for a total of 72 case pairs. When the alleged neonatal outcome was poor, there
      was a significant tendency to respond that evidence of hypoxia was present (P =
      .007) or that the obstetrician had made an incorrect decision (P < .001).
      CONCLUSION: Obstetricians are biased by knowledge of poor neonatal outcome when
      retrospectively interpreting fetal heart rate tracings and judging
      appropriateness of obstetric care.

PMID- 9583071
TI  - Gestational diabetes mellitus. Risk factors, obstetric complications and infant
      outcomes.
AB  - OBJECTIVE: To evaluate risk factors, obstetric complications and infant outcomes
      in women with gestational diabetes mellitus (GDM). STUDY DESIGN: We performed a
      population-based, longitudinal study of 824 women diagnosed with GDM in Nova
      Scotia, Canada, between 1980 and 1993. Adjusted relative risks (RRs) with 95%
      confidence intervals (CIs) were estimated through logistic regression. RESULTS:
      After controlling for confounding variables, the following were associated with
      an increased incidence of GDM: maternal age, prepregnancy weight, previous
      spontaneous or induced abortion (RR 1.41, 95% CI 1.18-1.68), previous stillbirth
      (RR 1.80, 95% CI 1.08-3.01), previous low birth weight infant (RR 1.48, 95% CI
      1.03-2.14), previous high-birth-weight (HBW) infant (RR 1.51, 95% CI 1.18-1.93)
      and chronic hypertension (RR 2.03, 95% CI 1.19-3.44). The relationship between
      maternal age and prepregnancy weight with GDM was nonlinear; women over age 35
      and with a prepregnancy weight < or = 49 kg or > 65 kg demonstrated an increased
      risk. Urinary tract infection, polyhydramnios, oligohydramnios, chronic
      hypertension with superimposed preeclampsia, mild preeclampsia and uterine
      bleeding of unknown origin occurred more frequently in women with GDM than in
      those in whom the diagnosis was not made. HBW infants were more likely to be born
      to women with GDM than to women without GDM. Finally, women with GDM were over
      twice as likely to undergo cesarean birth (RR 2.30, 95% CI 1.99-2.65).
      CONCLUSION: The risk of developing GDM is greatest in women over age 35, when
      prepregnancy weight is < 49 kg or > 65 kg and in those with chronic hypertension.
      Pregnancies complicated by GDM are at risk and need to be monitored closely for
      obstetric complications and adverse infant outcomes.

PMID- 9583072
TI  - Congenital adrenal hyperplasia. Molecular characterization.
AB  - OBJECTIVE: To study the molecular defects of congenital adrenal hyperplasia
      (CAH). STUDY DESIGN: Twenty Chinese patients, including 8 with salt-wasting (SW)
      type CAH, 11 with simple virilizing (SV) type CAH and 1 with nonclassical (NC)
      type CAH, were recruited. Two rounds of the polymerase chain reaction (PCR) were
      used to study the 21-hydroxylase gene (CYP21). The primary PCR amplified CYP21
      specific DNA fragments, and the secondary PCR used products from the primary PCR
      for analysis of amplification-created restriction sites (ACRS) and direct DNA
      sequencing. In all patients, ACRS analysis was done at 12 possible mutation
      sites, and then direct DNA sequencing was performed to confirm or define the
      molecular defects. RESULTS: Ten different mutations, including nine point
      mutations and gross gene deletion or conversion, were found in this study. Of the
      nine point mutations, eight could be easily detected by ACRS analysis. The three
      most common mutations were codon (CD)172 t-->a (I172N), IVS-II 656 c/a-->g, and
      gross gene deletion or conversion, accounting for 27.5% (11/40 alleles), 25%
      (10/40) and 20% (8/40) of all identified mutations, respectively. All SW patients
      were compound heterozygotes of IVS-II 656, gross gene deletion or conversion, or
      other severe defects, including CDs236 (t-->a) (I236N)+ 237 (t-->a) (V237E)+ 239
      (t-->a) (M239K), CD306 (+t), CD318 (c-->t) (Q318X) and CD356 (c-->t) (R356W)
      mutations. All SV patients had one allele with a CD172 (I172N) mutation. One
      allele of an NC patient had a CD183 (c-->g) (D183E) mutation, and the other
      allele was not defined. In the whole series, four alleles (10%) had more than one
      mutation. CONCLUSION: We found 10 different mutations in this study. The
      correlation between genotypes and phenotypes was compatible with the reported
      data. Two rounds of PCR and ACRS analysis may provide important information for
      genetic counseling, prenatal diagnosis and management of families at risk for
      CAH.

PMID- 9583073
TI  - Maternal CA-125 levels in pregnancy and the puerperium.
AB  - OBJECTIVE: To determine the levels of CA-125 throughout pregnancy and the
      puerperium to establish a baseline, thereby indicating what values may be
      indicative of the pathologic conditions usually associated with elevated CA-125
      levels. STUDY DESIGN: A prospective, longitudinal study was carried out on a
      consecutive series of pregnant women to determine their CA-125 levels throughout
      pregnancy and during the puerperium. Blood was drawn at four- to six-week
      intervals for clinically indicated tests. The residual sera were kept frozen, and
      subsequently CA-125 measurements were determined by radioimmunoassay. RESULTS: Of
      34 women enrolled in the study, 20 completed the evaluations throughout pregnancy
      and in the puerperium. The remaining 14 had evaluations for varying portions of
      their pregnancies but not throughout pregnancy or during the puerperium. The
      results in these two groups were compared and found not to be statistically
      significantly different. For the group as a whole, the levels of CA-125 were
      high, with wide fluctuations in the first trimester; the levels in the early
      first trimester (five to eight weeks) were particularly high, with a mean of 55.8
      and median of 36.2 (range, 6.9-251.2) U/mL. The levels then dropped and remained
      < 35 U/mL through the rest of pregnancy (including immediately prior to
      delivery). Another peak, with wide fluctuations, occurred soon after delivery,
      with a mean of 39.8 and median of 41.9 (range, 10.7-296.7) U/mL. In the late
      postpartum period (2-10 weeks after delivery) there was a return to baseline
      levels in all subjects. CONCLUSION: This study showed that there is a distinct
      pattern in CA-125 levels during pregnancy and the puerperium. Due to the wide
      fluctuations in CA-125 levels in very early pregnancy and the immediate
      postpartum period, CA-125 values during these periods are not useful for clinical
      correlation with the pathologic conditions known to be associated with elevated
      levels of CA-125. However, further study is needed to determine whether extreme
      values in the first trimester or elevated levels after the first trimester are
      diagnostic or predictive of any conditions related to pregnancy.

PMID- 9583074
TI  - Cornual pregnancy after IVF-ET. A report of three cases.
AB  - BACKGROUND: Ectopic pregnancy is a well-known complication of in vitro
      fertilization/embryo transfer (IVF-ET). Although ectopic pregnancy after IVF-ET
      in patients with prior bilateral salpingectomy is uncommon, it can occur and may
      be a cornual implantation. Because of the possibility of early rupture with
      severe hemorrhage, special attention to cornual pregnancy after IVF-ET is
      warranted. CASES: Three cases of cornual pregnancy occurred after IVF-ET. Two of
      these patients had prior bilateral salpingectomy, whereas another had prior
      tuboplasty for tubal disease. CONCLUSION: Patients who had prior salpingectomy or
      tuboplasty with cornual patency undergoing IVF-ET are at risk for cornual
      pregnancy. Close monitoring of pregnancies in these patients is important to
      prevent a deleterious delay in treatment of a cornual pregnancy.

PMID- 9583075
TI  - Staphylococcus aureus causing chorioamnionitis and fetal death with intact
      membranes at term. A case report.
AB  - BACKGROUND: Neonatal infection without premature rupture of amniotic membranes
      occurs in 1-2% of births. The prevalence of membrane inflammation among term
      births is approximately 10%. There has been only one case report of
      Staphylococcus aureus as the cause of chorioamnionitis with intact membranes.
      CASE: A 24-year-old woman was admitted at 38 weeks of pregnancy with labor pains.
      On admission, she had a slight fever of 37.8 degrees C, but the other physical
      findings were within normal limits. There were no symptoms or signs of membrane
      rupture. Fetal heart monitoring showed slight tachycardia, 160 beats per minute,
      and loss of variability. Fetal death was detected when the fetal monitoring was
      resumed after being interrupted for 30 minutes. A male infant weighing 2,920 g
      was born dead. Artificial rupture of the membranes had been performed just before
      delivery. CONCLUSION: Culture specimens from the placenta and cord blood showed
      growth of S aureus, and histologic examination revealed chorioamnionitis. The
      bacteriologic evidence from the infant clearly identified S aureus.

PMID- 9583076
TI  - Subcutaneous terbutaline pump.

PMID- 9583077
TI  - [Aldose reductase in the polyol pathway: a potential target for the therapeutic
      intervention of diabetic complications].
AB  - Aldose reductase (AR), an enzyme in the polyol pathway, catalyzes the reduction
      of glucose to sorbitol. Sorbitol is subsequently converted to fructose by
      sorbitol dehydrogenase. The two enzymes constitute the sorbitol (polyol) pathway,
      the alternate route of glucose metabolism. The acceleration of this pathway and
      ensuing metabolic imbalances have been postulated to play a key role in the
      pathogenesis of diabetic complications. Using a transgenic animal model
      expressing human AR, we defined the primary role of this pathway in the
      development of functional and structural abnormalities elicited by diabetes. The
      inhibitors for AR would thus become effective therapeutic agents for diabetic
      complications. As AR is a member of the structurally related, NADPH-dependent
      aldo-keto reductase superfamily, other members of this family, coexisting with
      AR, may interact with the inhibitors to quench their action against AR. With our
      new immunoassay system, the levels of AR expressed in diabetic patients can be
      measured directly. The enzyme levels were significantly associated with the
      presence of complications, indicating that variable levels of AR expressed in
      diabetic individuals may affect the susceptibility or development of pathological
      changes associated with diabetes. In this review, recent advances in the
      understanding of the pathophysiological significance of AR are presented that
      would aid in the effective pharmacological intervention of diabetic
      complications.

PMID- 9583078
TI  - [Functional activation of glial cells in early and delayed episodes of the brain
      damage].
AB  - Recent studies have indicated that glial cells such as astrocytes and microglia
      are activated in an early and delayed episode after brain damage. However, the
      mechanism and function of glial activation are still unclear. I examined whether
      the induction of inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1)
      and major histocompatibility complex (MHC) antigen was involved in the glial
      activation. The microinjection of interferon-gamma and lipopolysaccharide into
      rat hippocampus induced MHC class II and iNOS in microglia. The iNOS induction
      may be involved in the activation of tyrosine kinases and transcription factors
      such as signal transducer and activator of transcription-1 (STAT1) and nuclear
      factor-kappa B (NF-kappa B). Subsequently, neuronal cell death occurred in the
      hippocampus, but cell death was undetectable in both microglia and astrocytes
      that expressed HO-1. Thus, induction of iNOS and HO-1 in glial cells may be
      involved in hippocampal neurodegeneration and resistance to oxidative stress in
      glial cells, respectively. In Alzheimer's disease (AD) brains, iNOS expression
      was at a very low level, although STAT1 and NF-kappa B were significantly
      increased. Also, Bcl-2, Bcl-x, Bak, Bad and p53 were increased in AD brains.
      These observations suggest that oxidative stress and glial activation without
      iNOS induction may be involved in neurodegeneration of AD brains.

PMID- 9583079
TI  - ['Cut-open' method: a new method for Xenopus oocytes that enables intracellular
      perfusion and stable current recording].
AB  - Xenopus oocytes are one of the most widely utilized expression systems for
      voltage-dependent ion channels. Here, 1 describe a new technique for voltage
      clamp recording of Xenopus oocytes that enables fast and stable monitoring of
      transmembrane current as well as intracellular perfusion by cutting a part of the
      plasma membrane to open the cytoplasm to the recording chamber which is filled
      with artificial intracellular solution. The original method was developed and
      described by Dr. E. Stefani and his colleagues, and I have modified it by
      employing a push-pull cannula to exchange the intracellular solution. The main
      features of this technique are: 1) High frequency response and relatively low
      current noise; fast activation and deactivation of ionic currents can be
      precisely evaluated. 2) Stable recording conditions lasting for several hours;
      this is a marked advantage over the conventional and patch-clamp recording. 3)
      Control of the ionic composition of both the internal and external media; the cut
      open configuration enables desired manipulation of the internal milieu of oocytes
      easily, which is suitable for the study of Ca2+ channel modulation by second
      messengers and drugs.

PMID- 9583080
TI  - [Effect of lafutidine, a novel antiulcer agent, on healing and relapse of acetic
      acid-induced gastric ulcer in rats].
AB  - Effect of lafutidine ((+/-)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2-pyr
      idyl] oxy-(Z)-2-butenyl] acetamide, FRG-8813), a novel antiulcer agent, on the
      healing and relapse in acetic acid-induced gastric ulcer in rats was
      investigated. Lafutidine at 1, 3 or 10 mg/kg, twice daily for 10 days reduced the
      ulcer area in a dose-dependent manner, and the effect by 10 mg/kg of lafutidine
      was significant. The effect of famotidine at 1 mg/kg and cimetidine at 30 mg/kg,
      which have almost equal antisecretory activity to lafutidine at 10 mg/kg, on the
      ulcer area was not significant. Effect on the healing and relapse was assessed by
      endoscopy for 25 weeks after the induction of gastric ulcer. Drugs were
      administered twice daily for 11 weeks. Lafutidine at 3 mg/kg and famotidine at 1
      mg/kg accelerated the healing, but cimetidine at 30 mg/kg did not. Cumulative
      relapse rate and inflammatory cell infiltration were significantly reduced in
      rats initially treated with lafutidine. Famotidine and cimetidine had no effect.
      In conclusion, lafutidine accelerated ulcer healing and prevented ulcer relapse
      in rats.

PMID- 9583082
TI  - Accessible knowledge about the effectiveness of homoeopathic therapy.

PMID- 9583081
TI  - [Assay for oxidative stress injury by detection of luminol-enhanced
      chemiluminescence in a freshly obtained blood sample: a study to follow the time
      course of oxidative injury].
AB  - To evaluate occurrence of oxidative stress in circulating blood, we developed
      standard methods to assess (1) granulocytes status as a source of reactive oxygen
      species (ROS) and (2) lipid peroxidation (LPO). A simplified and highly sensitive
      assay was developed by utilizing the chemiluminescence (CL) from luminol oxidized
      by ROS. 1. The CL, from 300 microliters medium containing 1% blood, 10
      micrograms/ml luminol and 0.025 microgram/ml phorbol myristate acetate, well
      reflected the primed granulocyte status induced by in vitro contact with
      lipopolysaccharide (LPS). This CL was weakened slightly by superoxide dismutase
      and catalase, but markedly decreased by sodium azide. 2. We determined the
      optimal conditions for the t-butyl hydroperoxide (t-BuOOH)-stimulated CL method
      to evaluate plasma LPO in experiments on rat plasma added with
      phosphatidylethanolamine hydroperoxide (PEOOH). The CL from 300 microliters
      medium containing 6.67% plasma. 10 micrograms/ml luminol and 5 mumol/ml t-BuOOH
      was proportional to the added PEOOH amount. The integrated CL of the plasma with
      0-60 nmol of PEOOH gave values of 8.280-14.213 x 10(6) counts/60 min/tube. 3.
      Only 100 microliters of freshly drawn blood was enough for the two CL methods to
      detect the generation of ROS and the occurrence of LPO. These CL methods enabled
      the determination of the time course of oxidative stress occurrence in
      circulating blood of rats treated with 5 mg/kg LPS, i.p.

PMID- 9583083
TI  - Aminoalkanolic derivatives of xanthone with potential antiepileptic activity.
AB  - Synthesis, physicochemical and anticonvulsant properties of some
      aminoisopropanoloxy derivatives of 2-xanthone are described. The compounds were
      prepared by the amination of 2-[(2,3-epoxy)-propoxyl]-xanthone or 2-(3-chloro-2
      hydroxy-propoxy)-xanthone. The obtained compounds were evaluated for
      anticonvulsant activity in the maximal electroshock (MES)- and subcutaneous
      pentylenetetrazole (scMet)-induced seizures and for neurotoxicity in the rotorod
      test in mice and rats. The most promising compounds seem to be the 3-(tert.-butyl
      amino) (3), 3-[N-methyl-(tert.-butyl)-amino] (12) and 3-[4-(benzyl)-1-piperazinyl
      (5) substituted 2-hydroxy-1-(2-xanthonoxy)-propane from which 3 and 5 were active
      in both the anticonvulsant tests. The protective index (TD50/ED50) in MES in mice
      for 3 and valproate, as for 12 and phenytoin or carbamazepine, is similar.

PMID- 9583084
TI  - [Synthesis and cardiotonic activity of pyrazolylpyrimidines].
AB  - A series of pyrazolylpyrimidines was prepared by the reaction of
      hydrazinopyrimidines and pyrimidinecarbohydrazides with acetylacetone, and was
      screened for cardiotonic activity in papillary muscles and atrium of guinea-pig
      hearts. Many of these compounds were found to be active, and 2-(4,5-dimethyl
      pyrazol-1-yl)-4-thioxo-6-methyl-4 H-pyrimidine (1c), 2-methylthio-pyrimidine-4-yl
      hydroxyacet-(5-hydroxy-3,5-dimethyl)- 1-5 H-pyrazolide (7a) and 2-methylthio-4
      oxo-4 H-pyrimidine-3-yl-acet-(5-hydroxy-3,5-dimethyl)-1-5 H-pyrazolide (7b)
      showed the most positive-inotropic effects. The ED50 values are close to those of
      milrinone.

PMID- 9583085
TI  - Spectrophotometric determination of thiols in human lymphocytes.
AB  - A spectroscopic method for thiol analysis, based on the complexation reaction
      with Pd(II), is described. The proposed method is simple and sensitive and can be
      used for a rapid analysis of thiols in human lymphocytes.

PMID- 9583086
TI  - Evaluation of buccoadhesive metronidazole tablets: microbiological response.
AB  - Metronidazole has been found beneficial in a number of oro-dental infections
      namely dry socket, gingivitis, smelling tumours and periodontal diseases where
      anaerobes are implicated as pathogens. Buccoadhesive tablets of metronidazole
      were prepared by compressing the drug, bioadhesive polymers namely Carbopol-934P,
      a cellulose ether derivative, mannitol and suitable flavouring and sweetening
      agents. The tablet showed good release in vitro. It was subjected to in-situ
      release studies using bovine cheek pouch membrane in a flow through cell. The
      concentration was found to be above the MIC of the drug over the entire period of
      the release studies. The samples were tested against anaerobic strains commonly
      found in oro-dental infections. Since anaerobes are very slow growing
      microorganisms, a method for testing their susceptibility to metronidazole
      solutions was developed which can be used for other bioadhesive formulations
      which are active against anaerobes.

PMID- 9583087
TI  - Interferon- and streptolysin O-induced activation of protein kinases and
      inhibition of cytochrome P450-dependent monooxygenases in rats.
AB  - Immunostimulants known to initiate cytokine production were found to decrease the
      activity of hepatic microsomal drug oxidative enzymes but to activate protein
      kinase C (PKC). The present study investigated the effects of immunostimulating
      doses of rat interferon-gamma (IFN, 670,000 units i.p.) and streptolysin O (SLO,
      100 HU/kg i.v. for 5 days) on hepatic soluble, membrane-bound and nuclear PKC, 7
      ethylresorufin-O-deethylase (EROD) and 7-pentylresorufin-O-deethylase (PROD) in
      male Wistar rats. The SLO- and IFN-mediated decrease of EROD and PROD activity
      was associated with a characteristic activation of the hepatic and spleenic PKC.
      In SLO- and IFN-treated animals activities of the cytosolic, membrane-bound and
      nuclear PKC were significantly higher than in respective controls. Our results
      suggest that a decrease in hepatic cytochrome P450 content as well as the
      decrease in the EROD and PROD activities are inversely related to the function of
      PKC.

PMID- 9583088
TI  - Studying the reaction between clozapine and glutathione with element-selective
      detection.
AB  - The target of these investigations was a study of covalent binding the
      antipsychotic drug clozapine and the tripeptide glutathione. Other workers,
      primarily using radioisotopes, have found many adducts of clozapine and
      glutathione. We wanted to see how well the chlorine atom in clozapine could serve
      as an alternate to the use of a radiolabel using the Chemical Reaction
      Interface/Mass Spectrometer technique with HPLC introduction (HPLC/CRIMS). Here,
      we examine the capabilities of two such schemes that were previously used with GC
      introduction: Cl detection with SO2 as the reactant gas; and Cl and S detection
      using NF3 as the reactant gas. Detecting chlorine as HCl with SO2 was
      accomplished giving linearity over an 80-fold range of sample size. Incubations
      of the drug and glutathione with a peroxidase/peroxide system system yielded
      several metabolites characterized as novel conjugates of clozapine by
      electrospray mass spectrometry. This tentative identification of two conjugates
      was confirmed by examining the incubation mixture with NF3 as the CRIMS reactant
      gas. The simultaneous appearance of both Cl and S is consistent with covalent
      binding of clozapine to glutathione. A nearly doubled ratio of S to Cl in one
      peak confirmed the presence of a di-glutathione conjugate. These experiments
      support our proposition that element selective detection of HPLC effluents with
      CRIMS can supply additional information, not previously available using
      radioisotopic methods.

PMID- 9583089
TI  - Glutathione disulfide formation during naproxen metabolism in the isolated rat
      hepatocytes.
AB  - As naproxen was found to induce lipid peroxidation in liver microsomes and
      isolated hepatocytes of rats during its oxidative metabolism, we studied changes
      of glutathione on its metabolism. Intracellular oxidized glutathione (GSSG)
      content increased in isolated rat hepatocytes during naproxen metabolism. The
      intracellular GSSG increased preceding the production of thiobarbituric acid
      reactive substances (TBARS) and the release of lactate dehydrogenase (LDH). The
      glutathione-depleted hepatocytes treated with diethymaleate (DEM) enhanced TBARS
      production and LDH release, compared to the untreated hepatocytes. The production
      of GSSG may possibly be an early stage of the naproxen-induced oxidative stress
      which leads to lipid peroxidation and lethal cell injury.

PMID- 9583090
TI  - Effect of repaglinide upon nutrient metabolism, biosynthetic activity, cationic
      fluxes and insulin release in rat pancreatic islets.
AB  - This study aims at gaining further insight into the mode of action of repaglinide
      in pancreatic islet B-cells. At a 1.0 mumol/L concentration, the meglitinide
      analog failed to affect the metabolism of exogenous D-glucose and that of
      endogenous nutrients in islets prelabeled with either L-[U-14C]glutamine or [U
      14C]palmitate. Likewise, repaglinide (1.0 mumol/L) failed to modify significantly
      the incorporation of L-[4-3H]phenylalanine into TCA-precipitable material in
      islets exposed to a close-to-physiological concentration of D-glucose (7.0
      mmol/L). The threshold concentration for the insulinotropic action of repaglinide
      was close to 0.1-1.0 mumol/L and a maximal response was reached at 10.0 mumol/L
      in islets incubated in the presence of 5.6-8.3 mmol/L D-glucose. At a higher
      hexose concentration (16.7 mmol/L), however, an enhancing action of repaglinide
      (10 mumol/L) upon glucose-stimulated insulin release was only observed over 25
      min stimulation in perifused islets, no significant increase in insulin output
      being detected when islets were exposed to repaglinide (0.1 mumol/L to 0.1
      mmol/L) over 90 min incubation at the high D-glucose level. The increase in
      insulin output evoked by repaglinide in the islets perifused at 16.7 mmol/L D
      glucose coincided with a modest increase in 86Rb outflow and a marked stimulation
      of 45Ca efflux from prelabeled islets, suggesting stimulation of Ca2+ influx into
      the islet cells and subsequent activation of Ca(2+)-responsive K+ channels. When
      the administration of repaglinide was halted, the reversibility of its cationic
      and secretory effects was more pronounced in islets perifused at a high (16.7
      mmol/L), rather than a low (6.0 mmol/L), D-glucose concentration. These findings
      support the view that the primary site of action of repaglinide consists in a
      remodeling of cationic fluxes, and document that this drug displays favorable
      attributes as an insulinotropic agent for the treatment of non-insulin-dependent
      diabetes, such as its lack of interference with nutrient metabolism and
      biosynthetic activity in isolated islets, the low threshold concentration for its
      insulin-releasing action and its capacity to augment, at least transiently,
      insulin release at a high concentration of D-glucose.

PMID- 9583092
TI  - Tolerance and pharmacokinetics of ciprofloxacin in the chick. Preliminary
      experience in subjects of pediatric age with urinary tract infections (UTI).
AB  - We studied the tolerance and pharmacokinetic parameters of ciprofloxacin in (2
      mg/kg, i.v.) in 45 chicks. Serum concentrations of ciprofloxacin at various times
      of drawing (15 min, 30 min, 1 hr, 3 hr, 6 hr, 8 hr and 12 hr) peaked in the first
      15 min with a trough after 6 hr, and were completely absent after 8 hr. We found
      no neurotoxic effects or behavioral changes. Encouraged by a good tolerance for
      this quinolone, we conducted a preliminary study concerning the therapeutic
      efficacy of ciprofloxacin in 8 subjects of pediatric age (8-14 years) with
      urinary tract infections (UTI) that are resistant to classic antibiotics. The
      results and normality of hematologic parameters, checked before and after
      therapy, allow us to recommend the monitored use of ciprofloxacin in children
      with UTI resulting from bacteria resistant to other antibiotics.

PMID- 9583091
TI  - Measurement of intracellular Ca2+ concentration changes by use of fura-2 in the
      generation of myogenic contraction of dog cerebral artery in response to quick
      stretch.
AB  - In the present study, by using fura-2, we attempted to measure the changes of
      intracellular free Ca2+ concentrations ([Ca2+]i) in the generation of myogenic
      contraction of dog cerebral artery in response to quick stretch. Quick stretch
      was applied to rubber sheets or dog cerebral arteries at a rate of 10 cm/sec for
      30 sec with the amount of stretch equivalent to 40% of the initial length of
      materials. In rubber sheets and fura-2-unloaded cerebral arteries, the
      intensities of 500 nm fluorescence due to excitation at 340 nm (F340) and 380 nm
      (F380) were reduced by quick stretch although the ratio signal
      (F340/F380:R340/380) was not appreciably affected. F340, F380, and R340/380
      remained unchanged for 30 sec of the stretch period. By contrast, in fura-2
      loaded cerebral artery segments, before the appearance of delayed contraction in
      response to quick stretch, R340/380 was enormously raised by the mechanical
      stimulation. The stretch-induced myogenic contraction and the corresponding
      change in R340/380 were abolished by repeated stretches of the artery segments in
      Ca(2+)-free medium containing 0.2 mM EGTA or in the presence of papaverine (10(
      4) M). L-type Ca2+ channel antagonists (nicardipine and d-cis-diltiazem)
      inhibited both [Ca2+]i and mechanical activity of the cerebral arteries in
      response to stretch in a concentration-dependent and parallel manner. These
      findings indicate that changes of R340/380 in the generation of myogenic
      contraction of fura-2-loaded dog cerebral artery in response to quick stretch
      reflect those of [Ca2+]i in the response. Fura-2 seems to be a useful Ca2+
      indicator to measure the Ca2+ mobilization of vascular smooth muscle in response
      to quick stretch at the whole tissue level.

PMID- 9583093
TI  - Antitumor-activities of coumarin, 7-hydroxy-coumarin and its glucuronide in
      several human tumor cell lines.
AB  - Coumarin is found in many medicinal plants and therefore also used in
      phytomedicine for the treatment of venous diseases. The metabolic pathways of
      coumarin in the human body lead to the intermediate 7-hydroxy-coumarin and
      consequent glucuronidation in the intestine and liver. The antitumor activities
      of coumarin (C) and its known metabolite 7-hydroxy-coumarin (7-OH-C) were tested
      in several human tumor cell lines. C as well as 7-OH-C inhibited cell
      proliferation of a gastric carcinoma cell line, a colon-carcinoma cell line (Caco
      2), a hepatoma-derived cell line (HepG2) and a lymphoblastic cell line (CCRF CEM)
      in a concentration-dependent way, the IC50-values were 1.59-3.57 mM for C and
      0.68-2.69 mM for 7-OH-C. The glucuronide of 7-OH-C was ineffective in this
      respect.

PMID- 9583094
TI  - Molecular weight of hyaluronate in the serum of patients with chronic liver
      disease.
AB  - Hyaluronate in tissue and lymph is known to be heterogenous and to show a wide
      range of molecular weights (10(4) to 10(7) Da). Serum hyaluronate concentrations
      are increased under various pathophysiological conditions such as liver disease,
      post-gastrectomy, and after the ingestion of food. To clarify whether the
      chromatographic patterns of hyaluronate in serum from patients with chronic liver
      disease are different under these conditions, we subjected sera to chromatography
      using a Sephacryl S 400 HR column. The chromatograms revealed that the
      hyaluronate in serum was eluted as a single peak at the position corresponding to
      the molecular weight of blue dextran, the molecular weight being more than 2 x
      10(6) Da. The patterns of the chromatogram were similar among the patients with
      liver disease and the healthy subject although the heights of the peaks were
      different. Ingestion of food and a history of gastrectomy for gastric cancer did
      not influence the elution patterns of serum hyaluronate. These results indicate
      that hyaluronate in serum has molecular weight of more than 2 x 10(6) Da, and
      that its elution patterns are not influenced by pathophysiological factors, such
      as the severity of liver disease, or history of gastrectomy or by food intake in
      patients with chronic liver disease.

PMID- 9583095
TI  - Expression of interleukin-8 in human glomerulonephritis.
AB  - Interleukin-8 (IL-8) is a cytokine, which possesses both chemotactic and
      activating properties for neutrophils, lymphocytes and basophils. Various
      evidence has indicated IL-8 to be implicated in the pathophysiology of immune
      mediated renal diseases. We thus examined the expression of IL-8 in renal
      diseases. We detected the expression of IL-8 both in mRNA and the protein levels
      in renal biopsy specimens obtained from patients with IgA nephropathy and lupus
      nephritis. A significant correlation was found between the expression of IL-8
      mRNA and the number of neutrophils in the glomerulus. We also found a negative
      correlation between the expression of IL-8 mRNA and creatinine clearance. Our
      study thus suggested IL-8 to be involved in the pathophysiology of proliferative
      glomerulonephritis.

PMID- 9583096
TI  - Levels of serum glycosaminoglycans in renal failure.
AB  - We measured the concentration of serum glycosaminoglycans (GAGs) in patients with
      glomerulonephritis, renal failure and on hemodialysis using the dye binding
      method. In glomerulonephritis, concentration of serum GAGs did not increase, and
      there was no correlation between serum and urinary GAGs. In patients with renal
      failure and hemodialysis, concentration of serum GAGs was significantly lower
      than in controls. Concentration of serum GAGs was correlated with concentration
      of serum albumin, which is an indicator of malnutrition in patients on
      hemodialysis. One month of hemodialysis did not affect the concentration of serum
      GAGs in patients with renal failure, but six months of hemodialysis increased the
      concentration of serum GAGs. These results suggest that matrix production is
      suppressed in renal failure with malnutrition.

PMID- 9583097
TI  - Effects of hydrazine sulfate on galactosamine-sensitized endotoxic shock in ten
      day-old rats.
AB  - Patients who have liver diseases are susceptible to septic shock. Galactosamine
      induces liver damage and increases endotoxin-sensitivity. Hydrazine stimulates
      pituitary-adrenal axis and decreases mortality in galactosamine-sensitized
      endotoxic shock in the adult. However, as pituitary-adrenal function in the
      newborn is immature, the effects of hydrazine on galactosamine-sensitized
      endotoxic shock in the newborn remained unclear. In the present study,
      galactosamine-sensitized endotoxic shock was induced and treated with hydrazine
      in ten-day-old rats. Galactosamine (600 mg/kg) plus Salmonella enteritidis
      lipopolysaccharide (LPS; 0.01 mg/kg) induced hypoglycemia, lactacidemia and
      resulted in high mortality. Hydrazine at the dose of 20, 50 or 80 mg/kg did not
      alter the hypoglycemia, lactacidemia or morality. Dexamethasone ameliorated the
      hypoglycemia and lactacidemia (p < 0.05) and decreased the morality (p < 0.05).
      The lack of beneficial effects of hydrazine in galactosamine-sensitized endotoxic
      shock in ten-day-old rats may be related to immature pituitary-adrenal function
      and suppression of gluconeogenesis by hydrazine.

PMID- 9583098
TI  - [Hyperlipidemia in children and adolescents: diagnosis and therapy].
AB  - Severe hyperlipidemias should be diagnosed and treated even in childhood and
      adolescence, because vascular lipid deposition in the form of fatty streaks and
      progressive atherosclerotic lesions start to develop early in life. The
      heterozygous form of familial hypercholesterolemia found in about 1 of 500
      newborn infants, and polygenic forms of hypercholesterolemia, are the most
      frequent forms of primary genetic hypercholesterolemia found in children.
      Secondary hyperlipidemias, e.g. in diabetes mellitus, hypothyroidism and renal
      disease, are relatively frequent in children and adolescents and need to be
      searched for in the diagnostic evaluation, because they can be influenced by
      treatment of the underlying disorder. Children and adolescents with severe forms
      of hyperlipidemias should be diagnosed and treated early in life. Dietary
      modification is the basis of treatment of affected children and can lower LDL
      cholesterol by about 15-20%. In patients with severe hypercholesterolemia,
      dietary cholesterol intake should not exceed 150 mg/day in children or 250-300
      mg/day in adolescents. Even more important is a reduction of the intake of
      saturated fats and trans fatty acids and their replacement by polyunsaturated and
      particularly monounsaturated fats. Some additional lowering of LDL cholesterol
      may be achieved by the preferential use of vegetable over animal proteins and of
      complex carbohydrates over sugars. Repeated motivation, counseling and intensive
      practical training of the patient and family, supported by appropriate teaching
      materials, are essential for effective dietary treatment. Additional drug
      treatment is considered in children from the age of 8-9 years of age onwards if,
      in spite of adequate dietary modification, LDL cholesterol remains above 190
      mg/dl (4.9 mmol/l), or above 160 mg/dl (3.9 mmol/l) in the presence of additional
      risk factors. The drugs of first choice are anion exchange resins (colestyramine
      or colestipol) because of their well documented efficacy and safety. More
      convenient to take but often somewhat less effective is beta-sitosterol. If
      efficacy or compliance with resins or sitosterin is unsatisfactory, fibrates
      (e.g. bezafibrate, fenofibrate) may be considered as a drug of second choice.
      Cholesterol synthesis inhibitors are not recommended for general use in children
      at this time.

PMID- 9583099
TI  - [Insufficient understanding of second tumors after childhood neoplasms in
      Switzerland].
AB  - Second malignancy after childhood neoplasms is a well-known complication.
      However, frequency differs considerably according to the types of primary
      neoplasm and the specifics of therapy. Ten patients with a second malignancy
      after being cured of the primary tumor are described. There were 2 patients with
      acute lymphoblastic leukemia, one with non-Hodgkin's lymphoma, and one with
      breast cancer after Hodgkin's disease. Two patients with heritable retinoblastoma
      developed osteosarcomas in the irradiation field after a latent period of 7 and
      14 years respectively. There was another osteosarcoma in a Wilms' tumor survivor.
      One patient with acute lymphoblastic leukemia developed a secondary AML 10 years
      after achieving initial remission, and a meningioma was diagnosed in another
      patient with cured acute lymphoblastic leukemia. One patient died of peritoneal
      sarcomatosis of unknown origin 20 years after the diagnosis of acute myeloid
      leukemia. All patients received radiotherapy for the primary neoplasms. Secondary
      neoplasms in other patients were probably missed because they occurred in
      adulthood when the patients were transferred to other medical centres. It is
      impossible to trace these patients because central registration of patients with
      neoplasms is lacking. It is therefore important to establish a central cancer
      registry for the whole of Switzerland. Second malignancy after childhood cancer
      is not a rare event and requires long-term follow-up of patients with neoplasms.

PMID- 9583100
TI  - [Short and long term results of pulmonary balloon valvuloplasty in children].
AB  - Percutaneous balloon valvuloplasty is an alternative to surgical valvotomy for
      congenital pulmonary valve stenosis. Between 1985 and 1997, 73 valvuloplasties
      were performed in 70 patients, age range 1 day to 24.7 years. We reviewed the
      short- and long-term results in regard to transvalvular gradient and pulmonary
      insufficiency. The gradient was measured pre- and immediately post-valvuloplasty
      at catheterization and by Doppler echocardiography, and by echocardiography only
      at follow-up. Valvuloplasty was successful in 61/70 patients whereas surgical
      valvotomy was necessary in 9/70 because of a very dysplastic valve. A second
      valvuloplasty was performed in 3 patients presenting with restenosis. A 60%
      decrease in the gradient was noted immediately after the procedure, from 78.3 +/-
      24.5 to 33.7 +/- 19.7 mm Hg (p < 0.05). A follow-up of more than 2 years (4.2 +/-
      2.2 years) was obtained in 35 patients. A further decrease in the gradient was
      noted, to 20 +/- 12 mm Hg, and the degree of pulmonary insufficiency was mild in
      all patients except 2 with a moderate leak. The mortality was 0% and only 1
      patient had a complication (endocarditis). The short- and long-term results of
      pulmonary percutaneous balloon valvuloplasty are excellent. It can be considered
      the therapy of choice. The gradient shows a further decrease during follow-up due
      to regression of the infundibular muscular stenosis. Failure is attributed to
      very dysplastic valves and these patients may require, in a second stage, a
      surgical approach (patch enlargement and/or valvulectomy).

PMID- 9583101
TI  - [Mechanisms and prevention of restenosis after coronary angioplasty].
AB  - The success of PTCA is limited by late restenosis, which occurs in 30-50% of all
      cases, chiefly within the first six months after the intervention. Restenosis is
      due to the proliferation of smooth muscle cells and especially to overproduction
      of extracellular matrix in the arterial wall. The coronary intervention is
      followed by a not fully defined constrictive process of wound healing, so-called
      remodeling. Various alternative intervention techniques were investigated but did
      not show any clear advantage concerning restenosis compared to PTCA. Although the
      rate of restenosis is reduced by stent implantation, which hinders remodeling,
      the remaining intimal hyperplasia often leads to restenosis. In spite of
      promising results in animal models, to date no effective human pharmacological
      therapy has been found to prevent restenosis. To determine whether antioxidants,
      endovascular radiation or gene therapy show any benefit will require further,
      larger trials.

PMID- 9583102
TI  - [Nelson-Syndrome: 20 years after bilateral adrenalectomy for Cushing's disease].

PMID- 9583103
TI  - Pediatric patient is quite different from the adult.

PMID- 9583104
TI  - Growth and development of the child's cardiopulmonary system.

PMID- 9583105
TI  - Case of the season. Amebic abscess (Entamoeba histolytica) of the liver.

PMID- 9583106
TI  - Lung disease in premature neonates: impact of new treatments and technologies.
AB  - Advances in perinatal medicine and neonatology have dramatically changed clinical
      outcomes for premature neonates and have ushered in a new era of radiological
      complexity. "Portable" chest radiographs continue to be the mainstay in
      diagnostic imaging of fragile newborns, but radiologists may be confronted with
      new and unexpected radiological expressions of once-familiar disease processes.
      Familiarity with the radiological impact of emerging treatments in premature
      neonates is essential for accurate film interpretation.

PMID- 9583107
TI  - Anomalies and malformations affecting the fetal/neonatal chest.
AB  - Although significant anomalies of the fetal thorax are uncommon, with improvement
      in high-resolution ultrasonography, more of these lesions are being diagnosed
      prenatally. Accurate and specific prenatal diagnosis is important because
      different lesions have different natural histories and prognosis. Prenatal MRI is
      an increasingly important adjunct for identification and differentiation of these
      lesions and may help determine in selected cases when and if in utero fetal
      intervention is indicated.

PMID- 9583108
TI  - The effects of congenital heart disease on the lungs.
AB  - The alterations in anatomy and physiology, which often accompany congenital heart
      disease, may have a major impact on the child's lungs. These changes in pulmonary
      blood flow and ventilation are usually demonstrable on chest radiography and
      should be recognized as manifestations of the underlying lesion and not mistaken
      for primary lung disease. Correlation with the clinical history and physical
      examination are essential for correct interpretation, but radiological findings
      should be viewed objectively and without bias to provide accurate and valuable
      information to the treating physician.

PMID- 9583109
TI  - Pediatric diseases of the lower airways.

PMID- 9583110
TI  - Pneumonia in infants and children: radiological-pathological correlation.
AB  - The radiographic characteristics of pulmonary infection in children are many and
      varied. Although typical patterns are helpful in diagnosis, clinical and
      laboratory evaluation provide important diagnostic information. An understanding
      of the basic pathophysiology of infection and an appreciation of the anatomy of
      the child's growing lung help provide clearer, insightful, and more accurate
      radiological interpretation.

PMID- 9583111
TI  - Acute lung injury and acute respiratory distress syndrome in children.

PMID- 9583112
TI  - Pulmonary hemorrhage in children.

PMID- 9583113
TI  - Tumors of the pediatric chest.
AB  - A wide spectrum of malignant and benign diseases can present as tumors involving
      the chest in children. The imaging evaluation of these children is initially
      directed by clinical presentation and usually begins with a chest radiograph.
      Further imaging with CT, MRI, or rarely ultrasonography may be performed to
      better detect, localize, or characterize the lesion(s). The differential
      diagnosis of these tumors is guided not only by tumor location and
      characterization, but also by patient age and clinical presentation. Familiarity
      with the clinical and radiographic aspects of these diseases will help the
      radiologist to continue to play a crucial role in the diagnosis and management of
      these children.

PMID- 9583114
TI  - Thoracic deformities and the growing lung.

PMID- 9583115
TI  - [Inactivation of rat brain Na+ K+ ATPase by sodium dodecylsulfate: effect of pH,
      magnesium ions and temperature].
AB  - The relative stabilities to SDS inactivation of the rat brain Na(+)-ATPase
      catalytic subunit isoforms in the conditions of the surface charge modulation and
      temperature modification of the physical state of the membrane lipids were
      examined. The higher sensitivity of the Na+,K(+)-ATPase a1-isoform than a+ to SDS
      inactivation occurs under the conditions of the detergent treatment of microsomes
      at pH 7.5 and room temperature. The decrease in pH in ATP-free medium up to 6.2
      or temperature elevation up to 37 degrees C eliminates the differences in SDS
      sensitivity of the Na+,K(+)-ATPase isoforms. The enhancement of the SDS binding
      with a subunit due to changes in membrane surface charge in the first case or
      increase of accessibility of the protein intramembrane regions for detergent due
      to the decrease of the packing density of the boundary lipids in the second case
      are supposed.

PMID- 9583116
TI  - [Effect of incubation medium dielectric permeability on enzymatic activity of
      functionally different ATPases of smooth muscles].
AB  - Some organic solvents (2-10%) have been comparatively studied for their effect on
      purified transporting Ca2+, Mg(2+)-ATPase, solubilized from the plasma membrane
      of smooth muscle cells and on actomyosine ATPase of the smooth muscle. The
      inhibiting effect of solvents on the initial maximum specific activity of Ca2+,
      Mg(2+)-ATPase corresponds to the sequence dioxane > acetone > ethanol > dimethyl
      sulfoxide (DMSO). Like the case with Ca2+, Mg(2+)-ATPase, dioxane inhibits
      actomyosine ATPase; acetone, ethanol and DMSO stimulate ATP-hydrolase reaction
      which is catalyzed by the complex of contractile proteins. It is proved that the
      effect of the decrease of ATPase activity with decrease of incubation medium
      polarity is exceptionally determined by the value of incubation medium the
      dielectric permeability. This effect is independent of chemical nature of organic
      solvents which were used with the aim to obtain the corresponding values of D. It
      is supposed that the cause of activity inhibition of solubilized transporting
      Ca2+, Mg(2+)-ATPase under the effect of dioxane, acetone, ethanol and inhibition
      of activity of actomyosine ATPase as affected by dioxane is mainly connected with
      the increase of electrostatical interaction between opposity charged active
      centre of ATPase and the product (products) of ATP-hydrolase reaction (Mg ADP-,
      HPO4(2-)), which is induced by the decrease of incubation medium polarity (the
      decrease of D value). Stimulating effect of acetone and ethanol on actomyosine
      ATPase is probably determined by superposition of two components: that connected
      with direct effect of these solvents on the protein catalyst (interaction with
      enzyme with the future break of hydrogen and hydrophobic bonds in the protein and
      its "fluffing") and "electrostatic component" determined by the change of D value
      of the incubation medium. Possible role of electrostatic interactions between
      ATPases and reagents as the factor of non-specific control of catalytic activity
      of these enzymes is discussed.

PMID- 9583117
TI  - Effect of vitamin D3 and 1,25(OH)2D3 on growth of neoplastically derived cell
      lines and their alkaline phosphatase activity.
AB  - Inhibitory effects of 1,25(OH)2D3 and D3 on growth of four neoplastically derived
      cells were observed in human acute leukemia cell culture CEM-C-1 and CEM-C-7,
      human cervical carcinoma cell lines C-4-1 and human epithelioid carcinoma cells
      of cervix HeLa S3K. Concurrently, in dexamethasone-responsive cells C-4-1 and
      HeLa S3K there was a 1,25(OH)2D3 and D3 induced elevation of alkaline phosphatase
      with 1,25(OH)2D3 showing the greater effects. It is supposed that vitamins D3
      induced alkaline phosphatase activity in malignant cells, which is proposed to be
      a possible marker of cell differentiation, can be associated with the membrane
      effects of these vitamins.

PMID- 9583118
TI  - [Effect of ionophore A23187 and verapamil on RNA and DNA polymerase activity in
      rat liver nuclei].
AB  - It was shown that verapamil and Ca(2+)-ionofor A23187 essentially inhibited the
      activity of RNA-polymerase in isolated nuclei of rat liver, while DNA
      polymerasing activity was inhibited only after the addition of verapamil. These
      phenomena were not found after treatment of nuclei with 1% triton X-100. The
      inhibition of RNA synthesis was also found after the addition of Ca(2+)-ionofor
      A23187 but not verapamil to nuclei which envelope was disrupted by freezing
      thawing procedure. The data obtained suggest that Ca(2+)-ionofor A23187 and
      verapamil affected RNA and DNA synthesis in isolated nuclei.

PMID- 9583119
TI  - [Effect of 1,8-ANS on structural characteristics of cardiomyocytes sarcolemma].
AB  - The effect of sufan on structure properties of the rat cardiomyocyte sarcolemma
      was investigated. Fluorescence methods involving the probing with 1-anilino-8
      naphthalene-sulfonate or pyrene and the self-fluorescence of membrane proteins
      was used. Effect of sufan on the cardiomyocyte sarcolemma structure has been
      determined to provoke the conformational disturbances. These are the compaction
      of membrane proteins and translocation of their tryptophanyls from the surface to
      the interior of macromolecules. This process was accompanied by the increase of a
      protein plunge into the lipid matrix. Sufan induces a decrease of the
      microviscosity without a change of the polarity index in hydrophobic region of
      the lipid bilayer. These mechanisms have been supposed to be significant for the
      exhibition of sufan cardioactive properties.

PMID- 9583120
TI  - Influence of bioregulators on the phospholipid Langmuir monolayers.
AB  - Influence of bioregulators on the phospholipid Langmuir monolayers made of
      distearoylphosphatidylcholine and its equimolar mixture with
      dimitrystoylphosphatidylcholine was investigated. The results obtained allow
      concluding that the presence of physiologically active compounds in the subphase
      weakens the lipid-lipid interaction and increases the free energy change of air
      liquid interface in the case of pure distearoylphosphatidylcholine monolayers,
      but in the case of mixed monolayers it leads both to the increase and decrease of
      these parameters. Presence of the dimirystoylphosphatidylcholine molecules with
      the short fatty acyl chains in the monolayer destabilizes it. This effect is
      partially compensated by the interaction between lipid and subphase molecules.

PMID- 9583121
TI  - [Sequence homology in the primary structures of tyrosine kinase receptors of
      insulin superfamily and protein substrates of insulin type I and type II
      receptors].
AB  - Ligand-activated tyrosine kinase receptors of insulin superfamily peptides can
      realize the signal transduction to SH2-proteins (phosphatidylinositol 3-kinase,
      PI3K), protein phosphotyrosine phosphatase (PPTP), GRB2-adaptor protein in two
      pathways: 1) with participation of specific proteins--insulin receptor substrates
      1 and 2 (IRS1/IRS2); and 2) direct interaction between receptors and SH2-proteins
      (without IRS-proteins). Consequently, structural related determinants, which are
      responsible for the interaction with SH2-proteins, must be present in the
      receptor and IRS molecules. The comparative analysis of amino acid sequences
      (AAS) of human receptors of insulin, insulin-like growth factor-I and insulin
      related peptide and AAS of IRS1/IRS2 proteins allow one to identify for the first
      time the long homologous regions in their primary structures. After alignment of
      AAS of the regions, the sited-targets for tyrosine phosphorylation, most
      important for functional activity of tyrosine kinase receptors and IRS proteins,
      coincided with each other. These results show that some homologous regions can
      have similar function. Thus, the regions can involve in coupling the receptors
      and IRS-proteins with SH2-proteins, such as PI3K, PPTP, GRB2-adaptor protein. It
      is also possible that the homologous regions of tyrosine kinase receptors and
      IR1/IRS2 proteins mediate the interaction between their proteins.

PMID- 9583122
TI  - [Thermal denaturation of molecular complexes formed by single stranded RNA with
      tilorone].
AB  - The study of thermal denaturation for molecular complexes formed during
      interaction between phage MS2 single-stranded RNA and tilorone has been carried
      out. Both certain increase of Tm (by on 1.1) and the narrowing of complexes
      melting interval, delta T, (by 5.6 degrees C), have been detected. The value of
      hyperchromic effect, H, increases twice. The conclusion is made concerning the
      formation of double-stranded regions in single-stranded RNA molecules in the
      process of RNA--tilorone interactions. These results are discussed as an
      additional proof of our previous presumption concerning stabilization of
      spontaneously forming double-stranded RNA regions by tilorone binding.

PMID- 9583123
TI  - [Isolation of two fractions of hepatocytes and characterization of their lipid
      composition].
AB  - Two fractions of hepatocytes were isolated from the rat liver by nonfermentative
      method. These fractions were different for mechanical stability to the action of
      perfusion factors. It has been shown that cells of these fractions were
      differently separated in the linear density gradient of sucrose. It was connected
      with structural and functional heterogeneity of hepatocytes in the liver. Results
      obtained allow us to confirm that hepatocytes in the liver form at least two
      classes of cells with different lipid content. The plasmatic membranes of
      hepatocytes with high content of lipids were inclined to damage in the process of
      liver perfusion as compared to cells with low lipid content.

PMID- 9583124
TI  - [Peculiarities in a composition of surface lipids in coniferous leaves].
AB  - Composition on surface lipids of coniferous from Picea, Pinus and Larix genera
      (six plant species) are studied by spectral and chromatographic methods.
      Different content of carbonyl compounds in the summary fraction of surface lipids
      of coniferous, concerning componental content of hydrocarbon fraction and
      predominance of concrete fatty acids was shown. A substantial quantity of
      unethereficated fatty acids in surface lipids of plants is shown.

PMID- 9583125
TI  - Infrared spectra of bile, ionized, and conjugated bile acids.
AB  - The ionization and conjugation effect on infrared spectra of bile acids has been
      studied. The interpretation of spectra of native bile absorption in the infrared
      range was conducted with allowance for different types of functional groups
      oscillations.

PMID- 9583126
TI  - [Antioxidant enzymes activity of erythrocytes and indicators of blood
      hemodynamics of normal and hypoxic newborns in their first day of life].
AB  - The authors have found direct correlating between the enzymatic activity and the
      values of the total of circulation blood, erythrocytes, plasma and hematocrit.
      The highest activity of antioxidant-enzymes and values of hemodynamic was
      observed by the sixth hour of life of healthy newborns. Influenced by
      simultaneous effect of asphyxia and intrauterine chronic fetal hypoxia SOD,
      catalase, glucose-6-phosphate dehydrogenase activities in erythrocytes remain low
      during the first 24 hours of life. These newborns proved to have lower values of
      hemodynamics. The state of the antioxidant enzyme and hemodynamics at the moment
      of birth is discussed.

PMID- 9583127
TI  - [Exchange of vitamin D3 in placenta and fetal liver].
AB  - Metabolism of [3H]-vitamin D3 in placenta and fetus liver of rats on the 20-21st
      day of pregnancy was investigated. Biosynthesis in vivo of 25-hydroxyvitamin D3
      occurs in placenta and fetus liver and the maximum observed 25-hydroxylation
      composes 15% in placenta and 13% in the fetus liver. It has been shown, that C-25
      hydroxylation of vitamin D3 in the microsomal and mitochondrial fractions of
      hepatocytes take place. It has been concluded that placenta and fetus liver,
      although to not very much degree, is able to realize vitamin D3 metabolism
      independent of mother's organism.

PMID- 9583128
TI  - [Lipid composition of blood plasma and erythrocyte membrane of volleyball players
      under intensive physical load].
AB  - As the result of prolonged training activity highly skilled volleyball players
      have marked deficiency of fatty acids of w3 family both in the blood plasma as
      erythrocyte membranes. These acids may be used in the lipid peroxidation
      processes, that is proved by the facts of POL products content and their drawing
      into oxidation reaction, which is certified by high level of ATP in erythrocytes.
      Reduction of quantity of polyunsaturated fatty acids of w3 family may be regarded
      as results of their insufficient arrival with food.

PMID- 9583130
TI  - [Oxidative phosphorylation in liver mitochondria under extremely high frequency
      electromagnetic radiation in vitro].
AB  - Oxidative phosphorylation in the rat liver mitochondria under the influence of
      super high-frequency electromagnetic radiation was studied. Results have shown
      that the superhigh-frequency electromagnetic radiation in vitro did not affect
      the function of electron-transfer chain of tightly-joint mitochondria.
      Irradiation of mitochondria under partial damage of energetic joining promoted
      the reactivation of their function.

PMID- 9583129
TI  - [Endonucleolysis of chromatin in rat thymus and spleen lymphocytes after
      irradiation].
AB  - The level of soluble DNA fragments (polydesoxynucleotides) in thymus and spleen
      lymphocytes is enhanced 12 h after the whole-body X-ray irradiation in dose of
      0.5 and 1 Gy. The level of Ca2+, Mg(2+)-DNAase activity in lysed cells extracts,
      measured with calf spleen DNA, was enhanced in the region of 0.1-0.5 mM CaCl2 in
      incubation medium and decreased at 5 mM CaCl2. Monitoring of DNA fragmentation by
      electrophoresis in agarose gels showed the presence of fragments with
      approximately 200, 400, 800 bp length. X-ray induced DNA fragmentation is
      supposed to be associated with Ca2+, Mg(2+)-endonuclease activation.

PMID- 9583131
TI  - [Role of glutathione antiperoxide system in the mechanism of cytotoxic action of
      embichin].
AB  - Dynamics of changes in the peroxide level, contents of reduced and oxidized
      glutathione, activity of glutathione peroxidase and glutathione reductase in
      different organs of a rat under the influence of a single injection of embiquine
      in the dose of 1/2 DL50 was studied. Alkylating antitumor preparation was shown
      to cause the decrease of glutathione peroxidase and glutathione reductase
      activity. Activation glutathione antiperoxide system decreased cytotoxic effects
      of embiquine by prevention of lipoperoxid accumulation in the liver in the
      nearest periods of investigation after injection of the preparation, and in the
      kidney and spleen--during the whole period of investigation.

PMID- 9583132
TI  - [The peculiarities of pigment-protein composition of intergranular thylakoid
      fragments from maize chloroplasts].
AB  - The pigment-protein composition of two fractions of intergrana fragments from
      maize inbred lines F 7 and II 346 chloroplast had been investigated. It was shown
      that under electrophoretic separation of fraction 70,000 g from both lines and
      fraction 100,000 g from line F 7 the new band of pigment-protein complexes had
      been observed. It was determined that its polypeptide composition is the same as
      light-harvesting complex of PS II one, but it differs by low electrophoretical
      mobility. The conclusion was made that this is a new form of light-harvesting
      complex of PS II.

PMID- 9583133
TI  - [Blood serum enzymes in hypoxic syndrome].
AB  - Acute hypoxic hypoxia and hyperthermia have been studied for their effect on the
      activity of rat blood enzymes: lactate dehydrogenase, creatine phosphatase and
      gamma-glutamine transpeptidase. Simultaneous action of these unfavourable factors
      on the animals evokes a sharp change in activity of the studied enzymes. Membrane
      damaging effect of hypoxia and hyperthermia evidence for the necessity of
      pharmacocorrection at different stages of development of hypoxic syndrome.

PMID- 9583134
TI  - [Lipid peroxidation in thyroid tissue of people with diffuse toxic goiter].
AB  - The processes of lipids free-radical oxidation in euthyroid and thyrotoxic tissue
      samples of human thyroid gland were studied. It was shown, that the content of
      TBA-active lipid peroxidation products was considerably increased in thyrotoxic
      tissue of the thyroid, and the activity of antioxidant enzymes (catalase,
      glutation peroxidase) was decreased in it. Possible mechanism of the tissue
      lipoperoxide alternation under conditions of the thyroid hyperfunction is
      discussed.

PMID- 9583136
TI  - [Determination of rate and equilibrium constants for some typical biochemical
      reactions].
AB  - Three types of typical biological reactions are considered. Their kinetic curves
      plotted in the semilogarithmic scale are approximated well by two lines
      intercepting at different angles and may be described with the systems of
      differential equations. The latters are resolved as a complex system of
      transcendental irrational equations interconnecting the reagent concentrations,
      time and rate constants. A new method for numerical solution of such equations is
      suggested which permits determining the exact rate constants on the basis of
      either theoretical or experimental kinetic curves.

PMID- 9583135
TI  - [Effect of bee pollen extract on glutathione system activity in mice liver under
      X-ray irradiation].
AB  - It has been established that small x-irradiation dozes activate the lipid
      peroxidation and antioxidant system enzymes in mice liver. The introduction of
      bee pollen extract to animals normalized the activity of only several glutathione
      system enzymes in mice liver.

PMID- 9583137
TI  - [New bioactive compounds of the adrenal medullary layer].
AB  - The review of new data of the studies of the cerebral layers of eight
      cardioactive peptide and clieopeptide combinations. Research of the physical
      chemical and biochemical properties confirm nonidentity of these combinations to
      the known bioactive peptides of adrenals. The proteins connecting the factors
      under exploration have also been discovered, suggesting existence of cardioactive
      protein-peptide complexes in this region. Based on comparison of the studied
      chemical and biological properties of these combinations with the combinations of
      hypothalamic cardioactive neurohormones, in particular, with the neurohormone
      "C", a conclusion was made that combinations of the two regions are structurally
      and functionally related. The obtained data can be used in practical medicine for
      prophylactics and treatment of several cardiovascular diseases.

PMID- 9583138
TI  - [The reaction patterns of the hypophyseal-adrenal cortical system to repeated
      stressor stimuli].
AB  - The review systematizes and analyses the data about the influence of the repeated
      stresses on the activity of the hypothalamo-pituitary-adrenocortical system
      (HPAS). On the base of own results the author of the review affirms that the use
      of the graded stressors is necessary method of approach for the study of HPAS
      reactions to repeated stresses.

PMID- 9583139
TI  - [The patterns of behavioral activity in an uncertain environment].
AB  - Great amount of parameters of education regime in uncertain habitat's conditions
      is the main reason of contradictions in the present empirical data. It is
      reasonable to fulfill system analyses of conformity in natural laws of behavior
      in the framework of conventional-reflector experiment, taking into consideration
      that the grade of the habitat's uncertainty is mainly characterized by variation
      of the signal stimulus intensity, as well as the with probability of support.
      Existing statements and conceptions of organization peculiarities of behavior are
      regarded with absence of conventional stimulus (probabilistic education), acting
      of parathreshold and of suprathreshold intensity. It is marked, that despite of
      the already found conformities in natural laws, complex influence of factors of
      the probabilistic habitat on forming of behavior is not studied completely, there
      is only rough localization of optimum and pessimum zones in the parameter spaces,
      which influence education, there are no confident ways of prognosis and
      optimization of activity of the tested ones. Ways of further analyses of
      peculiarities of the system organization of behavior, in conditions of different
      grades of the habitat's uncertainty are suggested.

PMID- 9583140
TI  - [The physiological effects of the voluntary control of respiration in children
      and adolescents].
AB  - The information about the peculiarities of the forming the voluntary control of
      respiration in age aspects is produced in this article. It is shown, that the
      respiratory tests: voluntary hyperventilation and voluntary breath holding may be
      the convenient model for researching this problem. The irregular in the
      ontogenesis forming of the reactions of main physiological systems of the
      organism on the voluntary hyperventilation is revealed. The phase analysis of the
      duration of voluntary breath holding showed, that the volitional control of
      respiration begins to realize at 12 years old. The dynamics of the indexes of
      cardio-vascular system and CNS indicates of the high reactivity of vegetative
      nervous system of adolescents and of more distinct alterations in functional
      state of CNS in children in comparison with adults during voluntary breath
      holding. The sex distinctions in the mechanism of synchronization the internal
      rhythmic processes during the voluntary breath holding, especially in adolescents
      are revealed.

PMID- 9583141
TI  - [Liver functional disorders in traumatic stress].
AB  - The study conducts the analysis of liver dysfunctions in traumatic stress. The
      severe craniocerebral injuries, the skeletal bone injuries and the prolonged
      crush syndrome cause dystrophic changes of hepatocytes. The biochemical data
      testify the cytolytic syndrome and the liver insufficiency in patients with the
      traumatic disease. The hepatocytes metabolism disturbances and morphologically
      expressed dystrophy prove the development of the "traumatic hepatosis".

PMID- 9583142
TI  - [Heart fibroblasts, the mechanism of the appearance of their potentials and their
      possible role in regulating cardiac work].
AB  - Electrically non-excitable fibroblasts, which represent the other population of
      cells abundant in the sino-atrial node region, have been reported to be
      mechanosensitive in the frog and in the rat heart. It was shown that these cells
      respond to artificial or contraction-induced stretch of the atrial wall by a
      change in membrane potential. These changes could be explained by the operation
      of stretch-activated channels and intracellular calcium oscillation. Influences
      of cardiac fibroblasts on electrophysiological properties of cardiomyocytes would
      require interaction between these cells. In tissue culture studies, it has been
      shown, that fibroblasts and cardiomyocytes form nexus connections. In recent
      studies on fibroblast-cardiomyocyte junctions in the rabbit heart pacemaker
      region, non nexus-like contacts clearly dominated. These membrane non nexus-like
      contacts might promote capacitive interactions between heterologous cells, which
      has been demonstrated independently in electrophysiological studies. Through
      these contacts, the fibroblast membrane potential may affect the membrane
      potential of neighbouring myocytes in the right atrium which may play an
      important role for the chronotropic response of the heart to mechanical stretch
      of the right atrial wall. Electrically non-excitable but mechanosensitive cardiac
      fibroblasts can act as a substrate for an intracardiac mechano-electrical
      feedback mechanism by which mechanical changes, e.g. stretch, modulate the
      electrical activity. In the atria, fibroblasts may act as volume and mechanical
      sensors, respectively.

PMID- 9583143
TI  - [The characteristics of the surgical treatment of basal meningiomas with supra
      subtentorial spread].
AB  - The results of surgical treatment of 63 patients with basal meningiomas with
      supra-subtentorial spread were analyzed. The study has shown the effectiveness of
      one-stage tumor removal via supra-transtentorial approach with skull base bones
      resection. It is recommended to estimate an extent of operation on the basis of
      intraoperative assessment of biological behavior of the tumor, including
      interrelationship of tumor capsule and brainstem pia mater. Mortality rate was
      decreased from 23.8% to 11.1% following introduction of these principles.

PMID- 9583144
TI  - [The surgical treatment of medullocervical tumors].
AB  - The study included 12 operated patients with medullocervical gliomas. Two of them
      had hemangioblastomas, 6-ependymomas, 4-astrocytomas with different degree of
      dedifferentiation. The gross total tumor removals were achieved in 4 patients
      with ependymomas and patient with hemangioblastomas. Two patients with
      ependymomas and one with hemangioblastoma had their tumors removed subtotally.
      All astrocytomas were partially excised. The neurological long tract signs were
      alleviated almost in all ependymoma and hemangioblastoma patients after surgery.
      Complication rate was the highest in the astrocytoma group. The authors discussed
      indications and contraindications for surgery depending on the tumor type.

PMID- 9583146
TI  - [The classification of nervous system tumors].
AB  - The paper presents the classification of tumors of the nervous system, which is
      based on the Second Variant of the International Histological Classification of
      Tumors of the Nervous System which was developed by the WHO experts in 1993 and
      on the section "Morphology of Neoplasms" of the International Classification of
      Diseases, Xth review. These classifications were critically reviewed by taking
      into account the experience gained by the Laboratory of Pathomorphology,
      Academician N. N. Burdenko Research Institute, Russian Academy of Medical
      Sciences. The proposed classification may unify the material of our country's
      neurosurgical clinics and provide more corrective statistic data.

PMID- 9583145
TI  - [Craniocerebral suppurative-inflammatory complications in nervous system cancer
      patients in the postoperative period].
AB  - Retrospective analysis of case records of 9793 patients with brain tumors
      operated on at the Burdenko Neurosurgical Institute from 1985 to 1992 was done.
      323 patients (3.2%) had postoperative CNS infectious complications with deaths
      registered in 46 cases. Cholesteatomas and choriopapillomas had the highest
      complication rates: 12% of all cases and 11.4%, respectively. Variable incidence
      was observed in the glial tumors group: from 3% in glioblastoma patients to 4.7%
      in oligodendroglioma patients. Concurrent infections, surgical approaches via
      parabasal sinuses and CSF leakage at the operation site were considered as risk
      factors for postoperative CNS infectious complications.

PMID- 9583147
TI  - [Neurotransplantation in the treatment of the sequelae of the apallic syndrome].
AB  - The paper presents new results of embryonic tissue transplantation. Twenty-seven
      embryonic tissue transplantations into affected regions of brain cortex were
      performed on 21 patients with apallic syndrome. Motor and mental improvement were
      observed in sixteen recipients.

PMID- 9583148
TI  - [The results of microvascular decompression of the accessory nerve in patients
      with spastic torticollis].
AB  - The results of microvascular decompression of accessory nerve in patients with
      spastic torticollis are reviewed. 40 patients with spastic torticollis were
      treated. Unilateral microvascular decompression of the XIth cranial nerve were
      used in 11 cases, lateral in 23 cases. 5 patient had complete recovery, positive
      results were achieved in 12 patients. Best results were observed after bilateral
      decompression including retrocollis patients. Surgical treatment of laterocollis
      patients was less successful. Unilateral microvascular decompression of accessory
      nerve proved to be effective in homolateral type of torticollis.

PMID- 9583149
TI  - [Neurosonography in the surgical treatment of polycystic encephalopathy in
      children].
AB  - Intraoperative use of neurosonography in patients with polycystic encephalopathy
      was studied. Eight patients from 35 with diagnosed polycystic encephalopathy
      (PEP) were operated in 1985-1996. Neurosonography is the one of the most
      informative and effective intraoperative diagnostic tools in PEP patients. This
      method allows to visualize and control position and movements surgical
      instruments (catheters, needles, cannulas, etc.). It is also possible to drain
      the cysts located at different levels by changing the scanning view. Maximal
      effect can be attained only by simultaneous shunting of all cysts and ventricle.

PMID- 9583150
TI  - [Remarks on the pathogenesis of brain contusions occurring by a counterimpact
      mechanism in the acute period of their development].
AB  - Clinical course, CT, EEG and EP data as well as a cerebral blood flow and central
      hemodynamics parameters of 1727 patients with brain contusions were analyzed. It
      has been concluded that features of cerebral countercoup injuries do not match
      with definition of cerebral contusion. Countercoup injuries should be considered
      as secondary traumatic lesions with hemangiopathic and ischemic components. Their
      progress or regress depends on changes of CBF and integrity of vascular walls of
      regional vessels.

PMID- 9583152
TI  - [The clipping off of a giant fusiform aneurysm and the formation of a middle
      cerebral artery lumen by using a method for the intravascular aspiration of blood
      from the aneurysm].
AB  - The paper presents a 36-year-old patient in whom giant fusiform aneurysm of the
      M1 segment of the MCA was successfully clipped using intravascular aspiration
      technique. EEG was intraoperatively monitored. At surgery, the lumen of the
      deformed M1 segment was newly shaped by a series of 3 fenestrated clips.
      Intravascular aspiration of blood from the ipsilateral ICA significantly helped
      decrease blood volumes within the aneurysm and its size which facilitated
      dissection and clipping of the aneurysm. Since intravascular aspiration have been
      previously used during surgery of giant and large paraclinoidal aneurysms, this
      case demonstrates the benefits of the technique in the surgery of aneurysms
      located in the areas other than paraclinoid one.

PMID- 9583151
TI  - [The effect of multimodal pathogenetic therapy on microcirculatory function in
      combined craniocerebral trauma].
AB  - It is known that severe combined maxillocranial trauma causes impairment of
      microcirculatory vessels of bulbar conjunctiva as well as changes of local
      (cervical) and systemic blood flow, prevailing on the side of injury. New
      trigeminosympathetic regional block was used to produce chemical neurotomy of
      sympathetic and parasympathetic portions of autonomous nervous system in the
      neck. This blockade induced positive changes of minute CBF and microcirculation
      of CNS and facial area. Modified trigeminal sympathetic regional blockade along
      with intravenous infusion of dimephosphone improves both microcirculation and
      reparative-proliferative process in impacted area.

PMID- 9583153
TI  - [An approach to an esthesioneuroblastoma of the anterior cranial fossa via the
      anterior wall of the hypertrophied frontal sinus].
AB  - A 40-year-old patient with anterior cranial fossa esthesioblastoma was operated
      on. Surgical approach via anterior wall of enlarged frontal sinus was used. After
      removal of tumor from anterior cranial fossa, ethmoidal and frontal sinuses,
      skull base defect was closed with abdominal fat and periosteum. Different
      approaches to anterior cranial fossa are discussed.

PMID- 9583155
TI  - [A new method for treating the pain syndrome in coxarthrosis].

PMID- 9583154
TI  - [Primary malignant B-cell lymphoma of the cerebellum in an elderly female
      patient].
AB  - A 72-year-old woman with malignant B-cell cerebellar lymphoma was operated on.
      Postoperative combined chemotherapy was performed. Immunohistological
      investigations of specimen are demonstrated.

PMID- 9583157
TI  - [Cranio-orbital approaches to the skull base].

PMID- 9583156
TI  - [The use of a fiber-optic bronchoscope for the dynamic follow-up of the bulbar
      disorders in patients with tumors of the posterior cranial fossa].
AB  - Two case reports of patients operated for posterior fossa tumors complicated by
      postoperative hematoma are presented. In both cases patients underwent
      tracheostomy and were on ventilator for more than three weeks. Postoperative
      course was complicated by pneumonia and bronchitis. Fiberoptic bronchoscopy was
      performed to rule out lung complications. Fiberoptic laryngotracheoscopy was done
      for dynamic control of vocal cords paralysis and helped to make a decision
      regarding the time of the safe extubation.

PMID- 9583158
TI  - [A unified computerized data-base information system on brain trauma and
      diseases].

PMID- 9583160
TI  - [The recognition of visual images in a sensorially enriched environment: musical
      accompaniment].
AB  - Time of recognition by human subjects of masked Arabic numerals decreased and the
      probability of correct responses increased under conditions of listening of tape
      recordings of classic or rock music. Changes in recognition were most pronounced
      under the definite music power. The efficiency of recognition decreased during
      repeated listening of the same music fragments with unchanged power. The obtained
      data are considered as a manifestation of the dominant regularities.

PMID- 9583159
TI  - [Synaptic plasticity in the hippocampus during afferent activation reproducing a
      theta-rhythm pattern (theta plasticity)].
AB  - The data are reviewed concerning synaptic plasticity of the hippocampal
      monosynaptic pathways evoked by afferent activation which simulates activity of
      neurons in theta-rhythm. Activation with short high-frequency bursts applied with
      5 Hz frequency effectively induces long-term potentiation. In contrast,
      activation with single pulses at 5 Hz causes the depotentiation or even long-term
      depression of the activated synapses. "In-phase" activation of two afferent
      pathways in the theta-rhythm induces long-term potentiation, while the "out-of
      phase" activation induces long-term depression of a "weak"" pathway. A train of
      30-50 pulses at 5 Hz evokes heterosynaptic short-term depression, i.e., a
      suppression of all synaptic inputs for 1 min. So-called "hidden" plasticity (the
      enhancement of the effect of delayed activation in producing long-term
      depression) is also effectively evoked by the theta-like activatory patterns.
      Therefore, practically all known types of synaptic plasticity can be effectively
      evoked by the afferent activation which reproduce the pattern of the hippocampal
      theta-rhythm. These phenomena can underlie the theta-rhythm participation in
      learning and memory.

PMID- 9583161
TI  - [The effect of analogs of the C-termination fragment of arginyl vasopressin on
      the dynamics of the acquisition of an active avoidance conditioned reaction in
      rats].
AB  - The effect of original analogues of the 6-9 C-terminal AVP fragment, D-MRP and D
      MPRG, on the active avoidance behaviour of rats was studied using intranasal
      administration in a wide range of doses. The dose in 0.1 mcg/kg was the most
      efficient for D-MPR and 0.01 mcg/kg for D-MPRG, which for the tripeptide was ten
      times, and for the tetrapeptide hundred times lower than the corresponding dose
      of AVP used in the similar experiments. The tri- and tetrapeptide were shown to
      facilitate the active avoidance behaviour affecting both the formation of the
      reaction and consolidation of memory trace. The peptides mostly affect the
      perception processes, i.e., the detection of a specific stimulus from the
      environment, the estimation and memorizing of its biological significance.

PMID- 9583162
TI  - [The solving of the Revecz-Krushinskii test by rats of different genotypes].
AB  - Brown Norway rats bred from the original wild stock, KM (Krushinskii-Molodkina)
      albino rats selectively bred for audiogenic seizure susceptibility, and Wistar
      albino rats were subjected to Revecz-Krushinskii reasoning test. It determines
      whether rats can anticipate regular yet invisible shifts of food bait positions.
      A bait was placed under one of 12 opaque cylinders (arranged in a line) to be
      tipped by a rat in order to obtain food. In the first trial the cylinder 1 was
      baited, in the second trial the cylinder 2 was and so on up to 12th one. The
      correct strategy of this problem solving is a choice "one cylinder ahead" of the
      previous bait location. Rats appeared to be unable to realize this algorithm
      accurately. However, in some cases their performance was significantly different
      from chance. They apparently realized another strategy: to choose recently baited
      cylinders with shifting a zone of search. It was typical for brown and Wistar
      rats but not for KM which preferred to choose the cylinders baited in the
      previous trials, but their preference was not specified by recently baited
      positions. In the second experiment (learning of an accurate choice of one target
      cylinder with a fixed position in the line) the worst performance was found also
      in KM rats. The strain differences in Revecz-Krushinskii test performance are
      supposed to be caused by the level of spatial working memory.

PMID- 9583163
TI  - [The realization of a conditioned avoidance reflex in rats under conditions of
      the multiple activation of the globus pallidus dopaminergic system].
AB  - Daily bilateral microinjections of 15 or 45 mcg of amphetamine into the globus
      pallidus of rats within three weeks inhibited the realization of conditioned
      avoidance in a shuttle-box. The dose of 15 mcg was most effective. There were no
      changes in locomotor activity. In contrast to the results obtained earlier in the
      experiments with similar neostriatal microinjections, no stimulatory dopaminergic
      effects (stereotyped behavior) were observed. The differences are discussed in
      the roles of the pallidal and neostriatal dopaminergic systems in regulation of
      behavior.

PMID- 9583165
TI  - [The characteristics of the functional topology of Lashley's area in the rat
      cerebral cortex during different complex visual stimuli under alternative choice
      conditions].
AB  - In the result of our investigation it was determined: a) The ability to
      discriminate the complicated visual stimuli in rats depends on small part of
      occipital region of cerebral cortex critically. This is "Lashley zone". b) The
      location of this part of the cortex is the border between Ocl (17 field) and
      Oc2.1 (18a field), that and disagrees with the location of K. Lashley's "c" and
      "b" fields, although it includes largest part of "b" field.; c) The extirpation
      of this part of cerebral cortex leads to the irreversible loss of visual
      discrimination skill. But the control experiments demonstrated, that the ability
      to the keen visual differentiation and motor component of conditioned reflex were
      maintained.

PMID- 9583164
TI  - [The role of the epiphysis in forming a conditioned reaction to time in rats].
AB  - Pinealectomy impeded formation of time-conditioned reflex in the mode of fixed
      intervals. This was accompanied by a shortening of reaction latency and runs as
      well as by an increase in the number of intertrial responses. On the contrary,
      melatonin injection (0.1 mg/kg) facilitated conditioning by restricting the
      locomotion. It is suggested that pineal compounds have specific chronotropic
      properties.

PMID- 9583166
TI  - [The functional organization of exploratory activity during feeding and defensive
      behavior].
AB  - The experimental evidence is presented for the proposed hypothesis that searching
      activity has a heterogeneous functional structure, which includes the motivation
      power and cognitive information components. The quantitative characteristics of
      the first and second constituents are put forward as well as the ways of their
      determination in appetitive and defensive behavior. It was experimentally
      demonstrated that the characteristics of searching activity depended on modality
      and extent of motivation, repetition of searching situation, and sex.

PMID- 9583167
TI  - [Sexual motivation in male mice induced by the presence of the female].
AB  - Receptive female mouse placed in a cage behind a partition which prevented
      physical contacts but allowed the female to be smelt and seen produced in CBA and
      A/He males an elevation of plasma testosterone level and increase in time spent
      near the partition (TSNP) in attempts to reach the female. Both in CBA and A/He
      males the TSNP was much higher than in controls with empty adjacent compartment
      or with a male in it. The number of approaches to the partition was also
      increased but not sex-depended reflecting the general motor excitement of
      animals. A 3-4-fold increase in the TSNP preceding blood testosterone elevation
      was found within the first 10 min of female exposure. It was suggested that
      sexual motivation in males induced by female exposure was not caused by
      testosterone increase. The TSNP in male mice produced by female exposure can be
      used as an adequate index of sexual motivation.

PMID- 9583168
TI  - [The behavioral strategy of ants with a change in the level of food motivation].
AB  - Learning of ants was studied in a symmetrical multi-choice maze at different
      levels of food "social" motivation. A capability was shown of scout ants Myrmica
      rubra for changing rapidly behavioral strategy when the motivation level of a
      family changed from the low one for the high or vice versa. In the satiated state
      the ants demonstrated a clear-cut research activity. This activity was associated
      with high variability and instability of the maze habit. In the "hungry" state
      movement trajectories were rapidly minimized, the majority of ants used one
      dominant scheme of moving. Initial level of motivation determined the
      peculiarities of and learning and ability to transform behavioral strategies.

PMID- 9583169
TI  - [Facilitation and depression, under the influence of the iontophoretic
      application of acetylcholine, of the different components of the neuronal
      reactions in the cat motor cortex during the performance of a conditioned reflex
      of placing the paw on a lever].
AB  - The iontophoretic application of acetylcholine onto the motor cortex of cats
      during the execution of conditioned placing reaction caused an increase in
      neuronal excitability and facilitation of "extrinsic" connections (manifested as
      an enhancement of primary responses to electrical stimulation of the parietal
      cortex) and independent effect of suppression, which could be seen only in the
      response components with longer latency. The functional significance of these
      oppositely directed effects of acetylcholine application is corroborated by
      statistically significant changes in the motor response latency of the same
      directions as the changes in neuronal responses. Such a correlation was observed
      in a number of experiments.

PMID- 9583170
TI  - [The endogenous opioid system tonically activates the locomotor neurons in the
      mollusk Lymnaea stagnalis].
AB  - Keeping specimens of the pond snail Lymnaea stagnalis in the aqueous solution of
      the opiate antagonist naloxone (0.1 mM) or naltrexone (0.1 mM) resulted in a
      suppression of motor activity, and, particularly, in a decrease in the rate of
      ciliary locomotion. The activity of ciliomotor serotonergic neurons of the Pedal
      A cluster was intracellularly recorded in preparations of isolated ganglia.
      Naloxone (0.1 mM) suppressed, whereas the opiate agonists morphine (0.1 mM) and
      DAGO (0.05 mM) accelerated the synaptically driven firing of the Pedal A neurons
      both in preparations of the entire CNS and isolated pedal ganglia. The obtained
      results testify to the occurrence of tonic activatory influence of the endogenous
      opioids on the ciliomotor pedal neurons of snails and suggest that this influence
      is, at least partially, mediated by their synaptic input.

PMID- 9583171
TI  - [The assessment of the status of bottlenose dolphins Tursiops truncatus in the
      period after their capture].
AB  - Blood (eosinophil count and glucose content) and heart rate parameters were
      studied for assessment of individual responses and level of stress reaction of
      recently captured bottle-nosed dolphins Tursiops truncatus. Cross-tabulation
      analysis was carried out of the physiological parameters and the following
      process of adaptation to captivity. The normal level of stress response in
      contrast to excessive or abnormal responses were of the best predictive value for
      adaptation and survival of the animals. Correlation was found between the blood
      system parameters and heart rate variability in stress response assessment.

PMID- 9583173
TI  - [The properties of the benzodiazepine receptors in the rat cerebellum after acute
      seizures and the development of korazol-induced kindling].
AB  - The acute korazol (pentylenetetrazol) injection (50 mg/kg) induced seizures which
      were accompanied by a long-lasting (from 30 minutes to 3 days) decrease in
      benzodiazepine receptor (BDR) density (Bmax) in rat cerebellum without change in
      affinity. The density of the BDR was normalized on the 7th day after seizure
      termination. There were no differences in the initial BDR characteristics between
      the animals more sensitive to korazol (a dose of 25 mg/kg was sufficient for
      seizure induction) and less sensitive (30 mg/kg were ineffective). The chronic
      daily (for 24 days) administration of korazol in a subconvulsive dose led to an
      increase in seizure readiness (kindling). In 30 min after the last korazol
      injection the BDR density was decreased to the same extent as after the acute 50
      mg/kg korasol administration. The BDR density was normalized on the 7th day after
      kindling. It was demonstrated that the high-dose-induced and after-kindling
      seizures were underlain by the same mechanisms. The results suggest that the
      development of kindling depends on the state of the long-lasting receptors rather
      than the development of kindling forms the long-lasting reactions. The process of
      summation is at the basis of kindling development. The long-lasting decrease in
      activity of BDR receptors induced by a subconvulsive dose of korazol is summed
      with the following effect of the same dose.

PMID- 9583174
TI  - [Audiogenic seizures in rats of different genetic strains].
AB  - The temporal parameters of audiogenic seizures were compared in rats of different
      genetic strains (KM, Wistar, WAG/Rij, and GK). The probability of the origin of
      audiogenic fits was defined in each of the strains. It was found out that in
      Wistar, WAG/Rij, and GK rats the audiogenic fits developed as a double-wave
      pattern. In these strains the seizure intensity and their temporal parameters
      were the same but considerably differed from the intensive fits in KM rats, which
      developed as a one-wave pattern. The duration of the inhibitory pause between the
      first and the second wave in a double-wave fit was extremely stable, which could
      result from the spreading depression in one of the subcortical nuclei. Frequency
      spectra were compared of different kinds of stimuli applied for the audiogenic
      testing. Seizures were more easily provoked by the ultrasound signals with a
      complex structure. The resemblance is discussed between such signals and the
      natural communicative acoustic signals of rats as well as a possible role of
      emotional factor in the development of the audiogenic seizures.

PMID- 9583172
TI  - [The behavioral characteristics of rats induced by partial degeneration of the
      hippocampal cholinergic neurons].
AB  - The effects of intraventricular administration of ethylcholine aziridinium ion
      (AF64A) were studied in male Wistar rats. Bilateral injections of AF64A (3 nm/3
      mcl) reduced the reactions to biological alarm signal and produced a decrease in
      the open-field activity 3 weeks after this lesion. The lesioned rats also
      displayed deficit in retention of a passive avoidance task.

PMID- 9583175
TI  - [The anxiolytic action of an analog of the endogenous peptide tuftsin on inbred
      mice with different phenotypes of the emotional stress reaction].
AB  - The anxiolytic effect of the synthetic analogue of the endogenous peptide tuftsin
      (Thr-Lys-Pro-Arg-Pro-Gly-Pro) was studied in inbred mice Balb/c (C) and C57B1/6
      (B6) with different heritable types of emotional-stress reaction. In C strain
      with genetically high level of anxiety and "passive" type of behaviour under
      conditions of avoidable and unavoidable stress (open field, elevated plus-maze,
      light-dark chamber) the heptapeptide prevented manifestations of anxiety being
      administered intraperitoneally in a wide range of active doses (200-3000 mcg/kg).
      The drug did not change the behaviour of B6 mice with low level of anxiety and
      active type of emotional-stress reaction. The described effect is comparable with
      tranquilizing-activatory action of low doses of benzodiazepine tranquillizers,
      however, in contrast to the latter, the heptapeptide has no side inhibitory
      behavioural effects even in high doses. The heptapeptide may be considered as a
      promising new anxioselective drug without side inhibitory behavioural effects
      which are typical for benzodiazepine tranquillizers.

PMID- 9583177
TI  - Report on: East European Conference of the International Society for Invertebrate
      Neurobiology (ISIN)--Simpler Nervous Systems--held 9-12th September 1997, Moscow,
      Russia.

PMID- 9583176
TI  - [The current concepts of the nature and functions of sleep].
AB  - The paper presents a review of current papers concerning the functional
      significance of sleep in the whole and of its phases. A new hypothesis is
      proposed according to which the main sleep functions are body energy conservation
      and saving of plastic substances. The author reasons that the healthy human brain
      and the animal brain all the more do not become tired under low and moderate
      mental and physical loading in the day-time and, therefore, do not need sleep as
      rest.

PMID- 9583178
TI  - [The 41st annual meeting of Japanese Society of Nephrology. Tokyo, Japan. May 11
      12, 1998. Abstracts].

PMID- 9583179
TI  - [The 42nd Congress of the Japan Rheumatism Association. Tokyo, Japan. May 7-9,
      1998. Abstracts].

PMID- 9583180
TI  - [93rd annual meeting of Japanese Society of Psychiatry and Neurology. May 29-31,
      1997. Tokyo, Japan. Abstracts].

PMID- 9583181
TI  - Application of HPLC to the assay of enzymatic activities.

PMID- 9583182
TI  - Aging and beta-amyloid peptides decrease cholinergic receptor-mediated calcium
      increase in brain cortex synaptoneurosomes.
AB  - In this study, the muscarinic cholinergic receptor (MAChR)-evoked inositol 1,4,5
      trisphosphate (IP3)-mediated increase of cytosolic calcium concentration ([Ca]i)
      in synaptoneurosomes from brain cortex of adult and aged rats was investigated.
      In addition, the effect of two beta-amyloid (A beta) peptides, 1-28 and 25-35, on
      the resting and MAChR-induced increase of [Ca]i in brain cortex synaptoneurosomes
      of adult rats was evaluated. Release of IP3 was measured after prelabeling of
      synaptoneurosomal phosphoinositides with myo-[2-3H]inositol. Changes in [Ca]i
      were monitored by using fura-2 indicator. The effect of A beta peptides was
      evaluated following their preincubation with synaptoneurosomal protein for 1, 5,
      30 and 60 min. It was observed that in brain cortex synaptoneurosomes from aged
      rats, Ca(2+)-dependent and MAChR-mediated IP3 production was not changed in
      comparison with that estimated in adult brain, over 60 min of incubation.
      Activation of MAChR in synaptoneurosomes from brain cortex of adult rats for 10
      min increased [Ca]i by about 60% over its resting level (240 nM). This increase
      was completely blocked by muscarinic antagonists, atropine and pirenzepine, as
      well as by the antagonist of IP3 receptor, 8-(diethylamino)-octyl-3,4,5
      trimethoxybenzoate (TMB-8). In aged brain, there was no detectable change in
      resting [Ca]i (165 nM) due to MAChR stimulation. The 25-35 A beta peptide caused
      a time-dependent significant increase of resting [Ca]i in synaptoneurosomes from
      brain cortex of adult rats, which was almost five-fold after 60 min. In the same
      conditions, the action of 1-28 A beta peptide was statistically insignificant up
      to 30 min, then a rapid increase of resting [Ca]i by two-fold was observed up to
      60 min. Both A beta peptides decreased markedly the MAChR-dependent elevation of
      [Ca]i in respect to control (resting [Ca]i) in synaptoneurosomes from brain
      cortex of adult rats. These results indicate that beta-amyloid 1-28 and 25-35
      peptides may be involved in alteration of muscarinic receptor-mediated signal
      transduction during brain aging.

PMID- 9583183
TI  - Protein kinase C expression and activity in the human brain after ischaemic
      stroke.
AB  - We examined the expression of protein kinase C isoforms in infarcted tissue,
      penumbra and contralateral brain tissue from 10 patients who died between 1-52
      days after ischaemic stroke. Ten patients aged 61-89 years were used in the
      study. Tissue samples were assayed for protein kinase C activity using a non
      radioactive method, and specific isoforms expression determined by Western
      blotting and staining with anti-PKC polyclonal antibodies. There was a 2-24 fold
      increase in PKC gamma in the ischaemic penumbra of nine out of 10 patients
      compared to contralateral tissue. In infarcted tissue expression of PKC gamma was
      not significantly changed in any of 10 samples but the beta I isoform increased
      in eight and the beta II in nine patients. There was no significant change in
      expression in PKC alpha or in infarct or penumbra. Differences in total PKC
      activity were not specific in seven out of eight patients and it is difficult to
      estimate their significance. In conclusion after ischaemia there was an altered
      expression of PKC isoforms with an increase of PKC gamma in the surviving
      penumbra and beta I and beta II in the infarcted core.

PMID- 9583185
TI  - Mild hypothermia prevents the occurrence of cytotoxic brain edema in rats.
AB  - Hypothermia maintains the impermeability of the blood-brain barrier to proteins
      and, therefore, presumably the development of vasogenic brain edema after brain
      ischemia. We intended to determine whether mild hypothermia would have a
      protective effect against cytotoxic brain edema, the early stage of ischemic
      brain edema. Two groups of Wistar rats (37 degrees C and 35 degrees C body
      temperature) were subjected to 6 h of moderate decrease of cerebral blood flow
      (CBF) by means of permanent bilateral carotid artery ligation, and compared to a
      third group of unaffected animals. Carotid artery ligation induced a local
      cerebral blood flow (LCBF) reduction to 50-80% of baseline values. LCBF in the
      frontal cortex was restored to a higher level in hypothermic animals than in
      normothermic ones (P < 0.05). In normothermic animals, an increase of brain water
      content was detected in the frontoparietal and occipital cortex as well as in the
      hippocampus (P < 0.05), but only in one region of the frontoparietal cortex in
      hypothermic animals. The impermeability of the blood-brain barrier to proteins
      was shown by the absence of staining with Evans blue as an indicator of vasogenic
      brain edema. We conclude that mild hypothermia offers protection against the
      development of cytotoxic brain edema.

PMID- 9583184
TI  - Postnatal development of the rat striatum--a study using in situ DNA end labeling
      technique.
AB  - We have examined the development of rat striatum for evidence of cells dying in
      the process of physiological cell death. In present study we have indicated
      apoptotic cells in sections stained with cresyl violet (cell death characterized
      by pyknosis) or with DNA end labeling assay (TUNEL method). Our results
      demonstrated that cell loss during maturation of the rat striatum had the
      characteristics of apoptosis rather than necrosis. The greatest number of TUNEL
      positive and pyknotic cells in the striatum were found during the first postnatal
      days; after 7th day of postnatal life a rapid decrease of its number was observed
      after the second postnatal week no TUNEL-positive cells were observed in the
      striatum. Our analysis suggests that apoptotic cell death occurring during the
      development of striatal neuronal population takes place during the first week of
      postnatal life.

PMID- 9583186
TI  - The participation of nitric oxide in the facilitator effect of arginine
      vasopressin on memory.
AB  - In this study we tested the hypothesis that nitric oxide (NO), which function as
      a novel type of inter-cellular messenger in the central nervous system (CNS)
      participated in the facilitator effect of arginine vasopressin (AVP) on learning
      and memory. Recent investigations have provided evidences that inhibition of NO
      synthesis attenuated the vasodilatation caused by AVP, and inhibited the
      improvement of learning and memory evoked by angiotensin II. AVP as well as
      pharmacologically produced increase in endogenous NO facilitates the
      consolidation of shock avoidance learning. We evaluated the behavioural effects
      of AVP at dose 1 microgram after the inhibition of NOS by NG-nitro-L-arginine
      methyl ester (L-NAME) at dose 10 micrograms, and after the injection of
      endogenous donor of NO -L-arginine- 10 micrograms in the retrieval of passive
      avoidance situation, and in consolidation of active avoidance responses. The
      locomotor activity of all investigated drugs was tested in the open field test.
      AVP facilitated the recall of passive avoidance responses and consolidation of
      active avoidance responses. Neither the increase of NO concentration after the
      injection of L-arginine nor the decrease of NO after the inhibition of NOS by L
      NAME changed the behavioural effects of AVP. L-arginine increased the psychomotor
      behaviour and L-NAME decreased the activity of animals in the "open field" test.
      L-arginine itself improved the consolidation of active avoidance responses. Our
      results indicate that central action of AVP is probably independent of NO
      concentration in the brain.

PMID- 9583187
TI  - The influence of a doublet of stimuli at the beginning of the tetanus on its time
      course.
AB  - The influence of a pair of stimuli generated in a short time sequence (doublet)
      at the beginning of stimulation on the time course of the following tetanus was
      investigated. Experiments were performed on single motor units in rat's medial
      gastrocnemius. The doublet evoked an increase in tetanic tension, tetanic fusion
      and the area under tension record. These effects were measured in tetani fused to
      varying degrees. It was found that for all types of motor units the strongest
      influence of the doublet was observed in half-fused tetani. Moreover, the doublet
      influenced the first part of tetanus significantly more as compared to the
      second. Slow motor units showed greater sensitivity of the tension and the
      tetanus area to the doublet than fast units. The results show that slow units are
      characterized by better summation of their tension at the beginning of a tetanus.

PMID- 9583188
TI  - The effect of tonic pain on processing the non-painful stimuli indexed by late
      components of event-related potentials.
AB  - Event-related potentials (ERPs) evoked by light flashes and auditory tones in a
      standard odd-ball procedure were recorded from Fz, Cz and Pz scalp sites. Tonic
      pain was evoked by immersion of the hand in cold water (5 degrees C). Significant
      effects of pain were found in responses to target stimuli but not in responses to
      non-target stimuli. P300 wave was affected more than the earlier P200 component.
      The reduction of P300 amplitude was the strongest effect, both in auditory and
      visual tests. P300 latency was not significantly affected. Difference curves
      (target minus non-target ERPs) showed the additional effects: latency of P200
      component was elongated and its amplitude enlarged but only in auditory
      experiments. In control experiments with warm water stimulation no significant
      alterations of P300 or P200 components were found. The results show that the
      effect of tonic pain is specific: it predominantly affects the processes that
      manifest themselves as amplitude changes of P300 components in responses to
      target stimuli.

PMID- 9583189
TI  - ApoE polymorphism in Polish patients with Alzheimer's disease.
AB  - Alzheimer's disease is a genetically heterogeneous disorder of CNS. The presence
      of APOE-epsilon 4 allele is known to increase the risk of early and late onset
      sporadic and late onset familial forms of AD. In various Western European
      countries, USA, Canada, Japan and Australia the allelic frequency ranges between
      0.1-0.18 in controls, and between 0.24-0.52 in AD patients. In the present study
      on Polish population, we analyzed the frequency of APOE-epsilon 4 allele in
      persons with Alzheimer's disease (AD). APOE genotypes were determined in 30 mild
      to moderate AD (83%) and mixed dementia (MIX, 17%), as well as in 11 nondemented
      first-degree relatives of AD (NDR), recruited from AD patient registry in Warsaw.
      Among the AD and MIX patients the APOE-epsilon 4, epsilon 3, epsilon 2 allele
      frequency was 0.333, 0.65 and 0.017 respectively.

PMID- 9583190
TI  - Cortical excitability threshold for distal limb muscles in transcranial magnetic
      stimulation. Method--normative values.
AB  - Transcranial magnetic stimulation was carried out in 30 healthy subjects, aged 20
      to 55 and 156 to 180 cm tall, in whom cortical excitability threshold was
      determined for musculus (m.) abductor digiti minimi (ADM) and m. extensor
      digitorum brevis (EDB). The lowest stimulus intensity causing in the muscle a
      reproducible potential of an amplitude of 0.1 mV was adopted as the threshold
      value. The intensity of the stimulus was noted as a percentage of maximum
      stimulator output, defined as 100% (Magstim 200). In the stimulation of cortical
      areas for ADM, a circular coil (2.0T-530 V/m) was used while the in case of EBD,
      a double-cone coil (1.4T-660 V/m) was used. The threshold was noted while the
      muscle was relaxed and during weak voluntary contraction. The application of the
      double-cone coil allowed us to obtain for foot muscles similar threshold values
      as for hand muscles with a circular coil. It was confirmed that the threshold
      declines with voluntary contraction of the muscles under investigation. Normative
      values were prepared, with the norm, limits of the norm, outlier values and
      pathological markers being distinguished.

PMID- 9583191
TI  - Motor deficiency in Parkinson's disease.
AB  - The basal ganglia comprise a group of gray matter structures beneath the cerebral
      cortex, that surrounds the thalamus and hypothalamus. The basal ganglia play an
      important role in controlling movement. The motor circuits within the striato
      pallidal complex are thought to facilitate desired movement and inhibit unwanted
      movement through their influence, via the thalamus, mainly on cortical precentral
      motor regions. Localized damage to parts of the basal ganglia occurs in certain
      diseases such as Parkinson's disease. Parkinsonism is a common neurological
      disorder that affects about one person in every 1,000 of the general population
      and about 2% in the elderly. The diagnosis of Parkinson's disease is based on the
      presence of two or more of the major symptoms: tremor, rigidity, postural
      instability, and bradykinesia. The pathological process behind the motor
      disabilities of Parkinsonism is a progressive degeneration of dopaminergic
      neurons of the substantia nigra, that results in dopamine depletion in the
      striatum. Brain dopamine deficiency is sufficient to explain all of the major
      symptoms of Parkinson's disease.

PMID- 9583192
TI  - Children in especially difficult circumstances: the global and Philippine
      situation.

PMID- 9583193
TI  - Surface marker patterns of T cells and expression of interleukin-2 receptor in
      measles infection.
AB  - The surface marker patterns of T cells of Ghanaian children during measles
      infection were studied and an attempt was made to demonstrate T cell activation
      and viability in vitro after activation in vivo by measles virus. The frequencies
      of CD4+ and CD8+ naive T cells in measles patients were high while their memory T
      cells were remarkably reduced with no sign of proliferation even at the acute
      phase of the illness. The reduction of memory T cells was prolonged during the
      convalescent phase (2 months after onset). The anti-CD3 monoclonal antibody
      induced expression of interleukin-2 receptor alpha chain (IL-2R/CD25) was
      significantly suppressed; however, the addition of phorbol 12-myristate 13
      acetate or ionomycin caused a remarkable recovery of CD25 expression. On simple
      culture, an appreciable proportion of T cells from measles patients died rapidly
      in contrast with only a few T cells from healthy controls doing so. The
      suppression of CD25 expression was still demonstrated during the convalescent
      phase of the disease. Taken together these results suggest unresponsiveness and
      activation-induced cell death of T cells during severe measles infection in
      Ghanaian children. Furthermore the prolonged abnormalities of T cells (i.e.
      decreased memory T cells and inhibition of CD25 expression during the
      convalescent phase) might be related to post-measles infection immunosuppressive
      status.

PMID- 9583195
TI  - Effect of the season on the neurological outcome in children with cardiac arrest.
AB  - Twenty children who were successfully resuscitated after cardiac arrest (CA) were
      retrospectively studied to examine the hypothesis that children with CA may have
      a worse neurological outcome in hot weather than in cold weather. Of 7 children
      with CA in the cold season (atmospheric temperature < 14 degrees C), 4 in the
      warm season (14-24 degrees C) and 9 in the hot season (> 24 degrees C), 5 (71%),
      2 (50%), and 1 (11%), respectively, recovered consciousness (P < 0.05).
      Postresuscitative hyperthermia tended to be frequently observed in the group of
      children who suffered CA in the hot season, and it appeared to be associated with
      neurological damage. This preliminary study suggests that the neurological
      outcome of children with CA changes with the seasons, with a worse neurological
      outcome for CA in hot weather than in cold weather. A prospective study is
      required to determine whether, in a hot season or area, cooling of pediatric
      cardiac arrest victims during cardiopulmonary resuscitation on the scene improves
      the neurological outcome.

PMID- 9583194
TI  - Chronic effects of oral prostacyclin analogue on thromboxane A2 and prostacyclin
      metabolites in pulmonary hypertension.
AB  - Abnormal biosynthesis of thromboxane and prostacyclin has been implicated in
      patients with primary pulmonary hypertension and secondary pulmonary hypertension
      associated with congenital heart disease, and could be involved in the
      pathogenesis of pulmonary vascular disease. The chronic effects of an oral
      prostacyclin analogue, beraprost sodium, on thromboxane and prostacyclin
      biosynthesis and on pulmonary circulation were investigated in 15 children with
      pulmonary hypertension. The plasma concentrations of thromboxane B2 and 6-keto
      prostaglandin F1 alpha were measured, as was the urinary excretion of 11-dehydro
      thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, which are stable
      metabolites of thromboxane A2 and prostacyclin, respectively. In patients with
      pulmonary hypertension, the plasma concentration of thromboxane B2 and the ratio
      of thromboxane B2 to 6-keto-prostaglandin F1 alpha were greater than in healthy
      controls: 210 +/- 49 versus 28 +/- 4 pg/mL (P < 0.05) and 32.6 +/- 8.9 versus 5.7
      +/- 1.8 (P < 0.01), respectively. After 3 months of administration of beraprost,
      the plasma concentration of thromboxane B2 and the ratio of thromboxane B2 to 6
      keto-prostaglandin F1 alpha were reduced significantly: 210 +/- 49 to 98 +/- 26
      pg/mL (P < 0.01) and 32.6 +/- 8.9 to 18.0 +/- 6.7 (P < 0.05), respectively. In
      contrast, the plasma concentrations of 6-keto-prostaglandin F1 alpha in patients
      were slightly but not significantly higher than in controls, and did not change
      significantly after administration of beraprost. The concentrations of 11-dehydro
      thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha in urine correlated
      significantly with thromboxane B2 and 6-keto-prostaglandin F1 alpha,
      respectively, in plasma. Beraprost improved the imbalance of thromboxane and
      prostacyclin biosynthesis and has a potential efficacy for preventing the
      progressive development of pathological changes in pulmonary vasculature.

PMID- 9583196
TI  - Effect of carnitine supplementation on cardiac function in hemodialyzed children.
AB  - Thirteen carnitine-deficient children (mean age, 16.1 +/- 2.56 years) on a three
      times-weekly hemodialysis program for at least 1 year, and 11 healthy age matched
      children were involved in the study. All the patients had stable blood pressure
      and hemoglobin (Hb) levels with a maintenance dose of erythropoetin and none were
      digitalized. The total carnitine (TC) and free carnitine (FC) plasma levels were
      sampled prior to hemodialysis (HD) before and after 3 months of carnitine
      supplementation. A free carnitine (FC) to acylcarnitine (AC) ratio less than 4
      was defined as carnitine deficiency. Intravenous L-carnitine was injected at a
      dose of 20-40 mg/kg three times weekly at the end of each dialysis session for a
      3-month period. Echocardiographic examination was performed the day following HD,
      before and after carnitine treatment. Systolic and diastolic functions of the
      left ventricle, including the ejection fraction, were measured. Almost all the
      parameters were significantly different in controls and hemodialyzed patients. In
      carnitine-deficient hemodialyzed patients, 3 months of L-carnitine
      supplementation resulted in a significant increase in blood carnitine levels and
      the FC/AC ratio, but this was not associated with any significant improvement of
      cardiac function. Furthermore no significant changes were observed in plasma
      triglycerides, total cholesterol or other lipoprotein parameters before or after
      carnitine supplementation. Although there was a moderate increase in mean
      hematocrit (Hct) and Hb levels, these also did not reach statistically
      significant levels. These results suggest that the 3 months of carnitine
      supplementation is not sufficient to ameliorate cardiac function or increase Hb
      levels in children.

PMID- 9583197
TI  - Coronary risk factors in school children in relation to their family history of
      coronary heart disease and hyperlipidemia.
AB  - A school-based study was implemented to assess the family history of coronary
      heart disease (CHD) and hyperlipidemia (HL) in relation to serum lipoprotein and
      apolipoprotein levels. One hundred and twenty-five elementary school students
      (aged 9-10 years) and 297 junior high school students (aged 12-13 years)
      participated. Family history was evaluated by the following scoring method:
      positive family history in a parent, 2 points; in a grandparent, 1 point; and
      onset of CHD before age 60, 1 additional point. Family history of HL was positive
      in 8.2% of elementary school students, and 4.2% in junior high school students.
      Family history of CHD was positive in 11.5% of elementary students, and 11.0% in
      junior students. Family history score (FHS) for HL was related to serum total
      cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density
      lipoprotein cholesterol, apolipoprotein A-I, apolipoprotein B (apoB) and
      lipoprotein (a) in elementary students, and to TC, LDLC, triglyceride and apoB in
      junior students. There was no relationship between FHS for CHD and serum
      lipoprotein or apolipoprotein levels in any student. The children with a positive
      FH of HL already demonstrated an atherogenic lipid profile while those with FH of
      CHD did not, which was probably because lipid profiles in children are more
      genetically mediated by a FH of HL than of CHD.

PMID- 9583198
TI  - Relationship between fat distribution and lipid and apolipoprotein profiles in
      young teenagers.
AB  - The influence of obesity and fat distribution on serum levels of lipoprotein and
      apolipoprotein was investigated in 294 Japanese junior high school children (12
      13 years of age). Serum levels of low-density lipoprotein cholesterol (LDLC) (P =
      0.013), triglycerides (TG) (P = 0.0006), and apolipoprotein B (apoB) (P = 0.003),
      and the apoB/A-I ratio (P = 0.005) were significantly higher and serum levels of
      high-density lipoprotein cholesterol (HDLC) (P = 0.00003) and apoA-1(P = 0.003)
      were significantly lower in obese boys than in non-obese boys. The serum levels
      of TG (P = 0.013) and the apoB/A-I ratio (P = 0.011) were significantly higher
      and the serum levels of HDLC (P = 0.004) was significantly lower in obese girls
      than in non-obese girls. The LDLC/apoB ratio was lower in obese girls than in non
      obese girls (P = 0.03). Obesity (> or = 20% of ideal weight) was strongly
      correlated with the serum levels of lipids and apolipoproteins in boys; this
      relationship was less clear in girls. The degree of obesity and the body mass
      index (BMI) were more strongly correlated with serum levels of lipids and
      apolipoproteins in boys than in girls. In boys, atherogenic lipoproteins and
      apolipoproteins, such as LDLC and apoB, showed a stronger correlation with the
      thickness of the triceps skinfold, while in girls the anti-atherogenic
      lipoproteins and apolipoproteins, such as HDLC and apoA-I, showed a stronger
      correlation with both the triceps and the subscapular skinfold thicknesses. In
      girls the relationships between the BMI and the degree of obesity and the
      thickness of the subscapular skinfold (S) thickness were similar to the
      relationships between those parameters and the triceps skinfold (T) thickness. In
      boys, these parameters showed a stronger correlation with the subscapular
      skinfold thickness than with the triceps skinfold thickness. The correlation
      coefficients for the relationships between skinfold thickness and lipid and
      apolipoprotein levels were similar to the coefficients for the relationships
      between skinfold thicknesses and the severity of obesity and the BMI. The
      distribution of central-type fat accumulation, which is indicated by the
      thickness of the subscapular skinfold, the S/T ratio and S-T value, was inversely
      correlated with the HDLC level in both boys and girls. The degree of obesity was
      strongly correlated with the atherogenic lipoprotein profile in boys, in part
      because the subscapular skinfold thickness was strongly correlated with the
      degree of obesity and the BMI. In girls, the correlations between indices of
      central-type obesity and atherogenic lipid and apolipoprotein profiles were
      stronger than in boys. These data suggest that childhood obesity may be an early
      cardiovascular risk factor.

PMID- 9583199
TI  - Low levels of high density lipoprotein cholesterol in Turkish children: an
      important risk factor.
AB  - In Turkish adults, the incidence of coronary artery disease (CAD) has been found
      to be high. However, no detailed lipid, or lipoprotein data of children are
      available from Turkey. The present study was designed to define the borderline
      lipid and lipoprotein levels of sera in 397 healthy children (aged 5-14 years;
      206 boys and 191 girls). Mean levels of total cholesterol (TC), triglyceride
      (TG), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C,
      respectively) were found to be 150, 79, 46.7, and 87.6 mg/dL, respectively, for
      boys, and 152, 77.5, 46.3 and 90.5 mg/dL, respectively, for girls. Lipids and
      lipoproteins did not show any significant correlation with age and body mass
      index (BMI), except for TG in boys in whom TG levels were positively correlated
      with age and BMI. There were no significant differences in lipid and lipoprotein
      levels between boys and girls. As in the Turkish adult population, serum HDL-C
      levels of Turkish children were profoundly low on international comparison.
      Twenty-three (53%) of 43 children with low HDL-C level (< or = 35 mg/dL) had
      abnormal ratios of TC/HDL-C (> or = 5) and/or LDL-C/HDL-C (> or = 4.5), whereas
      only 13 (3.7%) of the remaining 354 children with a HDL-C level less than 35
      mg/dL had abnormal ratios of TC/HDL-C (> or = 5) and/or LDL-C/HDL-C (> or = 4.5).
      The low levels of HDL-C in Turkish children may be associated with the high
      incidence of CAD in the Turkish adult population.

PMID- 9583200
TI  - Should children with infection be tested for lipid, lipoprotein and
      apolipoprotein?
AB  - The lipid profile is known to alter in patients with infection, but there has not
      been a study of the apolipoprotein levels in serum of otherwise healthy children
      during infection. Lipids, lipoproteins, apolipoproteins A-1 and B and lipoprotein
      (a) were evaluated prospectively in 31 consecutive children, aged 4-15 years, who
      were admitted to the hospital with bacterial pharyngitis. The degree of
      dyslipidemia associated with bacterial pharyngitis was assessed using each child
      as his/her own control and by comparison with 79 healthy children who had not had
      an infection during the past 3 months. Serum total cholesterol, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-1
      and apolipoprotein B levels were significantly decreased during the symptomatic
      phase of the disease, whereas the serum triglyceride level was slightly elevated.
      Serum lipoprotein (a) concentration did not change significantly. In conclusion,
      it is suggested that serum lipids, lipoproteins and apolipoproteins should not be
      assessed during infection because of the possible transient changes of these
      parameters during infection or inflammation.

PMID- 9583202
TI  - Plasma and urinary platelet activating factor concentrations and leukotriene
      releasing activity of leukocytes in steroid sensitive nephrotic syndrome of
      childhood.
AB  - Platelet activating factor (PAF) is synthesized and secreted by glomerular
      mesangial and endothelial cells. It increases glomerular basement membrane
      permeability and induces proteinuria. Leukotrienes (LT) are mediators released by
      either leukocytes or glomerular cells under the PAF effect. The possible role of
      PAF in steroid sensitive nephrotic syndrome (SSNS) of childhood was studied in 8
      children with SSNS in the acute stage, 5 children in remission and 8 healthy
      controls. The PAF concentrations in urine and plasma were determined. Leukocytes
      were stimulated in vitro and the LT release in response to stimulation was
      determined. The urinary and plasma concentrations of PAF were significantly
      higher in the acute phase than in remission and in control patients. Children
      with SSNS were found to have peripheral leukocytes with increased LT releasing
      activity in vitro. These results are in accordance with clinical and experimental
      observations indicating that PAF originates in the kidney and plays a role in
      normal kidney physiology. Urinary PAF concentrations may be related to
      proteinuria because they were strongly correlated in the present study. Elevated
      plasma PAF concentrations in the acute stage of SSNS could result from either its
      secretion from the circulating leukocytes or decreased acetyl hidrolase activity
      needed for its hydrolysis in plasma. The increased LT release in vitro suggests
      that these cells might have been activated by PAF secreted from glomeruli. It is
      proposed that PAF and different LT in systemic and glomerular circulation are
      important mediators in childhood SSNS.

PMID- 9583201
TI  - Clinical value of glycated hemoglobin and fructosamine in the long-term glycemic
      control of children with acute lymphoblastic leukemia.
AB  - Hyperglycemia in children with acute lymphoblastic leukemia (ALL) has been well
      documented in the literature. The purpose of the present study was to evaluate
      the clinical value of glycated hemoglobin (GHb) and fructosamine (Frc) in the
      long-term glycemic control of ALL patients. An attempt was made to identify the
      risk factors for hyperglycemia in ALL patients. The study group comprised 26
      newly diagnosed ALL patients admitted to hospital during 1995-96. Patients with a
      history of blood transfusion or infection within the past 3 months were excluded
      from the study. White blood cell (WBC) counts, fasting blood glucose (FBG), GHb
      and Frc levels were analyzed in venous blood on screening day 0, before induction
      of chemotherapy. Frc analysis was repeated on the 21st day and GHb level on the
      60th day of chemotherapy. FBG tests were performed before each dose of L
      asparaginase, on days 21 and 60. None of the patients was obese. Although six
      children (23%) had hyperglycemia during the induction therapy, four of them had a
      GHb level higher than normal on admission. Only one patient who developed
      hyperglycemia had a family history of diabetes mellitus. Patients with a high
      initial WBC count (> 20 x 10(9)/L) had a significantly higher baseline GHb than
      patients with a WBC count below this level. GHb values returned to normal after
      achievement of complete remission. It is suggested that the leukemic process
      could impair glucose metabolism and baseline GHb may be used to monitor possible
      small changes in glucose homeostasis of ALL patients, prior to chemotherapy.

PMID- 9583203
TI  - Frequency of steroid sulfatase deficiency in Hiroshima.
AB  - A retrospective survey was performed between 1983 and 1995 to determine the
      frequency of steroid sulfatase (STS) deficiency in Hiroshima. Males with
      ichthyosis were diagnosed enzymatically. During 1979-95 in Hiroshima Prefecture,
      275,943 males were born and 28 had STS deficiency. The observed frequency of STS
      deficiency was 1 per 9855 males. Therefore, STS deficiency is fairly prevalent in
      Japan.

PMID- 9583204
TI  - Sialic acid in childhood renal diseases: correlation with clinical and laboratory
      indices.
AB  - There are many kinds of glycoproteins that have sialic acid residues and it has
      been reported that these are elevated in some renal diseases and their
      significance in the pathogenesis of several renal diseases has been investigated.
      In the present study the serum and urine levels of sialic acid were measured in
      healthy controls and in children with either poststreptococcal acute
      glomerulonephritis (PSAGN) or minimal change nephrotic syndrome (MCNS) to test if
      there is any correlation with clinical and laboratory indices. In PSAGN and MCNS
      patients the serum and urine sialic acid concentrations at onset and relapse were
      significantly different from healthy controls (Mann-Whitney U-test P < 0.005).
      There was not a significant correlation between the clinical severity, serum
      creatinine and complement C3 levels and serum sialic acid concentrations in PSAGN
      patients. Also there was not a significant correlation between edema, serum
      albumin, IgG, transferrin, alpha-1-antitrypsin and serum sialic acid
      concentrations in MCNS patients. Although high serum and urine sialic acid levels
      were found in both PSAGN and MCNS patients, it does not have any clinical
      significance nor is it important as a diagnostic or prognostic marker.

PMID- 9583206
TI  - Response of parathyroid hormone to anaerobic exercise in adolescent female
      athletes.
AB  - It has been shown that moderate exercise suppresses parathyroid hormone (PTH)
      secretion, while strenuous exercise is apt to induce continuous secretion, which
      has a negative effect on bone mineral densities (BMD). The present study
      investigated a typical response of PTH to brief exercise. The study group
      comprised six adolescent female basketball players whose BMD were within normal
      limits. Maximal anaerobic power by three-step cycling was loaded on each subject.
      The first blood sample was drawn 30 min prior to testing test, the second was
      immediately following, the third was 15 min after, and the fourth was 30 min
      after. The proportional change in plasma volume was -11.5% immediately following
      (P < 0.05), +2.1% 15 min after, and +5.5% at 30 min after exercise (P < 0.05).
      The expected value was calculated on the assumption of no effect, except changes
      in plasma volume, by exercise. The measured values of PTH and calcium (Ca)
      immediately after exercise were lower than each of the expected values (P < 0.05
      for both). At 15 min after, there was no significant difference between expected
      and measured values of PTH, Ca and magnesium (Mg), respectively. At 30 min after,
      the measured value of Ca and Mg was higher than each expected value (P < 0.05 for
      both). It was concluded that PTH secretion is suppressed transiently immediately
      after maximal anaerobic exercise and is then stimulated during the recovery time
      in normal BMD subjects.

PMID- 9583205
TI  - Growth hormone stimulation tests in chronic renal failure with metabolic
      acidosis.
AB  - Metabolic acidosis is one of the possible causes of growth retardation in chronic
      renal failure (CRF). Data about the effect of metabolic acidosis on growth
      hormone (GH) secretion in CRF are limited. A study was carried out on eight CRF
      patients, hospitalized because of severe metabolic acidosis, and eight age
      matched prepubertal healthy short children. Growth hormone stimulation tests were
      done with L-dopa and clonidine before or during acidosis therapy and after the
      correction of metabolic acidosis. The levels of GH were measured by radio
      immunoassay. The mean of the peaks of both tests were used for each patient and
      statistical significance was tested by Mann-Whitney U and Wilcoxon tests. No
      difference was found between the GH peaks of the two groups during acidosis and
      after the correction of acidosis (Wilcoxon test, P > 0.05). In view of this data
      it was concluded that metabolic acidosis has little effect on GH stimulation
      tests.

PMID- 9583207
TI  - Value of the urinary uric acid to creatinine ratio in term infants with perinatal
      asphyxia.
AB  - The diagnosis of perinatal asphyxia is often inexact and present techniques for
      assessing its severity are unsatisfactory. The purpose of this study was to
      describe prospectively the value of the urinary uric acid to creatinine (UA/Cr)
      ratio in showing increased uric acid excretion in early spot urine samples for
      the identification of perinatal asphyxia, and to assess the relationship between
      the urinary UA/Cr ratio and the severity of hypoxic-ischemic encephalopathy.
      Twenty-seven fullterm infants with perinatal asphyxia were compared with 40
      healthy controls. The UA/Cr ratio was higher in the asphyxiated group when
      compared with controls (2.11 +/- 0.83 vs 0.72 +/- 0.39 P < 0.001). Furthermore,
      there was a correlation between the UA/Cr ratio and the severity of the
      encephalopathy (r = 0.84; P < 0.001). The UA/Cr ratio was found to be a good,
      simple screening test for the early assessment of perinatal asphyxia.

PMID- 9583208
TI  - Acute myositis with transient decrease of albumin, immunoglobulin, and complement
      following rotavirus gastroenteritis.
AB  - A 2-year-old boy developed acute myositis associated with rotavirus
      gastroenteritis. He had remarkable swelling and subcutaneous edema, mostly in the
      legs, 4 days after the onset of gastroenteritis. Marked elevation of creatine
      kinase was observed while serum albumin, immunoglobulin, and complement were
      decreased.

PMID- 9583209
TI  - Severely decompensated abdominal Wilson disease treated with peritoneal dialysis:
      a case report.
AB  - A 12-year-old girl with severely decompensated abdominal Wilson disease was
      treated with abdominal dialysis in order to accelerate the excretion of chelated
      copper. Dialysate without human serum albumin or D-penicillamine was used and was
      able to accelerate the excretion of chelated copper, with an increment of 5.5
      19.7% compared with urinary excretion only.

PMID- 9583210
TI  - Neonatal erythema infectiosum.
AB  - A report is presented of a patient with neonatal erythema infectiosum who
      developed petechiae, transient thrombocytopenia and transient cardiac failure due
      to transplacental transmission of human parvovirus B19 (HPV B19) infection. It is
      suggested that the thrombocytopenia was caused by platelet-associated IgG
      produced by the patient, and that the cardiac failure may have been caused by
      direct entry of HPV B19 into the cardiac tissue.

PMID- 9583211
TI  - Inhaled nitric oxide followed by extracorporeal membrane oxygenation in
      resuscitating a newborn with hypoxemia.
AB  - In a newborn requiring cardiopulmonary resuscitation because of hypoxemia due to
      sepsis (oxygenation index > 40), inhalation of nitric oxide (NO) in a
      concentration of 16 p.p.m. improved oxygenation and restored spontaneous
      circulation. Cannulation for extracorporeal membrane oxygenation (ECMO) then was
      performed safely under NO inhalation. ECMO was discontinued on day 7, and on day
      14 the infant was extubated. During follow-up examination at 5 months of age no
      neurological abnormalities were found. This case shows the usefulness of
      combining inhaled NO and ECMO.

PMID- 9583212
TI  - Exercise-induced acute renal failure in a girl with renal hypouricemia.
AB  - A 10-year-old Japanese girl developed acute renal failure following a 100-meter
      dash during physical training at school. After the run, she experienced intense
      pain in the loins with nausea and vomiting lasting more than 12 h. On the
      following morning, she was found to have mild proteinuria and acute renal failure
      (ARF). Serum creatinine and blood urea nitrogen were elevated, but the serum uric
      acid level was normal (3.1 mg/dL). With recovery of renal function over the
      ensuing days, hypouricemia (0.6 mg/dL) became evident in the patient. Although
      the pathophysiological association between renal hypouricemia and ARF is not
      known, oxygen free radicals have been implicated in the pathogenesis for ischemic
      reperfusion ARF. Superoxide production by neutrophils stimulated by N-formyl
      methionine leucyl-phenylalanine was normal in the patient both before and
      following exercise. Pyrazinamide and probenecid tests were undertaken on both the
      patient and her parents, who had borderline hypouricemia, to determine their
      renal tubular handling of uric acid. Results showed that the patient and her
      mother had a subtotal reabsorption defect, while the father had defective
      postsecretory uric acid reabsorption.

PMID- 9583213
TI  - Liver transplantation in a case of hypoproteinemia and coagulopathy.
AB  - A female infant with hypoproteinemia and coagulopathy associated with
      hypertyrosinemia was successfully treated with living-related liver
      transplantation (LRLT). On the 12th day of life plasma amino acid analysis
      revealed a marked elevation of tyrosine, so the patient was fed on a low-tyrosine
      and low-phenylalanine diet. However, hepatosplenomegaly, hypotonia, alopecia,
      eczema and psychomotor delay did not improve and recurrent episodes of
      disseminated intravascular coagulation (DIC) caused her condition to deteriorate.
      Liver biopsy on the 230th day revealed marked fatty change accompanied by mild to
      moderate cholestasis. Therefore, LRLT from her father was performed on the 286th
      day resulting in improvement of all the aforementioned signs and symptoms.
      Despite a thorough examination, no diagnosis of a known disorder could be
      established. However, her elder brother had also been born with severe
      hypoproteinemia and coagulopathy, and died of DIC on the second day of life.
      Thus, the disorder is designated as a new entity, namely 'congenital
      hypoproteinemia and coagulopathy associated with hypertyrosinemia'.

PMID- 9583214
TI  - Myasthenia gravis with alopecia totalis.
AB  - Myasthenia gravis was diagnosed on the basis of a positive Tensilon test in a 4
      year-old male child with alopecia totalis. His scalp hair and eyebrows had began
      to disappear at the age of 10 months. No other physical abnormalities such as
      motor paralysis, were seen except for left ptosis and alopecia totalis. His serum
      titer of anti-acetylcholine receptor antibody was elevated. No immune system
      abnormalities (C3, C4, CH50, C-reactive protein, antinuclear antibody or
      lymphocyte function disorders) were detected. Although alopecia areata and
      alopecia totalis are sometimes present in adults with autoimmune diseases and
      myasthenia gravis, this association is rare in children. The present case
      represents the youngest patient with myasthenia gravis associated with alopecia
      totalis.

PMID- 9583215
TI  - Using polymerase chain reaction to detect the etiological virus of serologically
      non-A, non-B, non-C fulminant hepatitis in Japanese children.

PMID- 9583216
TI  - Direct resin-bonded, fibre-reinforced anterior bridges: a clinical report.
AB  - Direct resin composite cantilever bridges were placed in patients to replace 26
      single upper anterior teeth and one upper premolar. Twenty-four bridges were
      simple cantilevers, and three were fixed-fixed bridges. The bridges were
      constructed with hybrid resin composite placed around a resin-impregnated plasma
      etched polyalkane fibre bundle bonded to the abutment tooth enamel by the acid
      etch technique. Twenty-five bridges were assessed at 10 +/- 1 months. Two had
      fractured due to trauma, however, in both cases the pontic remained attached to
      the abutment tooth by the fibre bundle. This method of tooth replacement is
      viewed as a rapid, simple, cost-effective means of replacing anterior teeth in
      selected patients.

PMID- 9583217
TI  - An evaluation of bond strengths of denture repair resins by a torsional method.
AB  - Chemical cure resin materials are generally used in the repair of dentures.
      Different repair resins used may yield different results. The bond strength of
      three autopolymerizing resins were evaluated using a torsional test method. The
      results showed that Palapress and Caulk resins had a higher repair strength than
      Rapid Repair resin.

PMID- 9583218
TI  - A case of chronic severe neutropenia: oral findings and consequences of short
      term granulocyte colony-stimulating factor treatment.
AB  - Neutropenia is an absolute decrease in the number of circulating neutrophils in
      the blood which results in susceptibility to severe pyogenic infections. Various
      oral findings such as periodontitis, alveolar bone loss and ulceration may be
      seen in neutropenic patients. A case is presented of a 6 year old girl with
      chronic, probably congenital, severe neutropenia with frequent respiratory tract
      infections, recurrent oral ulcerations and significant periodontal break-down
      resembling prepubertal periodontitis. She was given granulocyte-colony
      stimulating factor (G-CSF) treatment which resulted in an increase in granulocyte
      count within two weeks and resolution of the neutropenic ulceration. It is
      suggested that G-CSF together with dental care regimens is a promising treatment
      model in chronic severe neutropenia cases presenting with oral manifestations.

PMID- 9583219
TI  - Minocycline and oral pigmentation.
AB  - Minocycline is a semisynthetic tetracycline used in the treatment of inflammatory
      acne because of its broad spectrum of activity, less common development of
      resistant organisms, and its anti-inflammatory effects. A number of adverse
      reactions are reported, including skin and oral pigmentation. This paper details
      the pharmacology of minocycline and describes the pigmentation and likely
      mechanisms active in both hard and soft tissues. Oral pigmentation usually
      involves the hard tissues only and presents typically as a discrete band
      occupying the central zone of the alveolar mucosa and palate. As with other
      sites, it may persist following withdrawal of the drug. Early recognition by the
      dental practitioner may allow an alternative form of therapy to be sought,
      minimizing the likelihood of a long-term aesthetic problem.

PMID- 9583220
TI  - Multiple supernumerary teeth. Case report.
AB  - The presence of supernumerary teeth, although not uncommon, occurs usually in the
      premaxillary region. Furthermore, examples of multiple supernumerary teeth in one
      patient are rare. A case involving the presence of multiple supernumerary teeth
      in all quadrants in described.

PMID- 9583221
TI  - Reducing the incidence of unerupted palatally displaced canines by extraction of
      deciduous canines. The history and application of this procedure with some case
      reports.
AB  - The procedure of extracting the deciduous canine to reduce the incidence of the
      unerupted palatally displaced canine was first described in 1951, and an article
      solely devoted to the technique appeared in 1959. The procedure then virtually
      vanished until 1981. A prospective study published in 1988 created the first
      widespread interest in the method which now appears in major texts. Why the
      procedure succeeds is uncertain. In the 1950s non-resorption of the deciduous
      canine was thought to cause palatal deflection of its successor and therefore it
      appeared appropriate to extract the obstructing deciduous tooth. It has been
      estimated that the technique should be successful in approximately one in three
      of all cases in the population aged 10 to 13 years. The earlier the detection the
      better the prognosis, because the unerupted canine frequently moves more mesially
      with time. Before the procedure is attempted it is important to discuss possible
      outcomes with the patient. Three successfully treated cases are illustrated. The
      first conformed with the guidelines of having an uncrowded maxillary arch and
      being aged between 10 and 13 years. The second was aged 15 years 2 months at
      commencement. An unsuccessful surgical exposure of the permanent canines followed
      by extraction of the deciduous canines was carried out in the third case.

PMID- 9583222
TI  - Combined endodontic-orthodontic and prosthodontic treatment of fractured teeth.
      Case report.
AB  - A case history of a 10 year old patient who accidentally injured his maxillary
      left central incisor is presented. The fracture of the crown extended about 4 mm
      below the crest of the alveolar bone. After pulpectomy and root canal therapy, a
      screw was cemented into the canal of the incisor. By means of a removable
      orthodontic appliance, the fractured tooth was extruded and the fracture line was
      brought above the level of the alveolar bone. The tooth was then restored with a
      veneer crown over a post core. A tooth that would have been extracted routinely
      was thus saved and restored through the use of a collaborative approach.

PMID- 9583223
TI  - Wine tasting and dental erosion. Case report.
AB  - A case of widespread dental erosion is reported in an individual who had worked
      in the wine industry for ten years. This occupation involved daily tasting of at
      least 20 wines, but often more. The erosion manifested as dental sensitivity with
      there being cervical erosion, occlusal pitting, and loss of enamel around
      restorations. The effect of immersing unerupted human teeth in white wine (pH
      3.3) was examined with the scanning electron microscope, where marked surface
      changes had occurred after 24 hours of exposure.

PMID- 9583224
TI  - The prevalence of Helicobacter pylori in practising dental staff and dental
      students.
AB  - Recent studies suggest Helicobacter pylori is spread by faecal-oral or oral-oral
      transmission. Gastroenterologists who are exposed to gastric secretions and
      saliva have a high prevalence of H. pylori infection. Venous blood was obtained
      from 92 dentists, 40 dental nurses, 33 fifth year and 30 first year dental
      students. An ELISA assay was used to detect H. pylori IgG antibodies. Results
      were compared with an age and sex matched normal population. The prevalence of H.
      pylori infection in dentists, dental nurses, fifth year dental students and first
      year dental students were 23 per cent, 18 per cent, 18 per cent and 16 per cent,
      respectively. There were no significant differences when compared with the normal
      population controls. The prevalence of H. pylori antibody was not significantly
      increased with years of practice or patient contact time in dentists and dental
      nurses. Helicobacter pylori infection is uncommon in dental professionals working
      in the oral cavity.

PMID- 9583225
TI  - Gingival crevicular fluid lactoferrin levels in adult periodontitis patients.
AB  - The present study was designed to determine in a cross-sectional study whether
      there was any relationship between the levels of lactoferrin in gingival
      crevicular fluid and clinical periodontal parameters. Crevicular fluid was
      collected from individual sites using standardized filter paper strips
      (clinically healthy sites, N = 23; periodontitis sites, n = 66) and evaluated for
      lactoferrin by enzyme-linked immunosorbent assay. The data showed that: (1) the
      total amounts of lactoferrin were 0.003-0.021 ng (30 second sample) (average
      0.009 +/- 0.005 ng) in a clinically healthy periodontium group and 0.016-3.847 ng
      (30 second sample) (average 0.575 +/- 0.069 ng) in adult periodontitis patients
      (statistically significantly higher in adult periodontitis patients); and (2) the
      total amounts of lactoferrin were significantly correlated with clinical
      parameters, especially a strong positive correlation with gingival crevicular
      fluid volume (r = 0.85, p < 0.01) and with probing depth (r = 0.71, p < 0.01).
      These results indicated that quantification of lactoferrin in gingival crevicular
      fluid may be a more sensitive indicator of periodontal pathology than traditional
      clinical indices.

PMID- 9583226
TI  - Candida-associated denture stomatitis. Aetiology and management: a review. Part
      1. Factors influencing distribution of Candida species in the oral cavity.
AB  - Candida species are yeasts and within the oral cavity, Candida albicans is the
      most frequently isolated. There is clear evidence that C. albicans adheres to
      oral surfaces including acrylic dentures and mucosa. The mechanisms of attachment
      differ, with candidal adhesion to inert surfaces under the control of hydrophobic
      and electrostatic forces and adhesion to mucosa dependent on a number of complex
      ligand-recognition systems. Other factors within the oral environment such as
      saliva, pH, bacteria and hyphal formation have been shown to influence adhesion
      of candida species to surfaces in the mouth.

PMID- 9583227
TI  - Identification of stroke prone patients by panoramic radiography.
AB  - Stroke (cerebrovascular accident, CVA) is the third leading cause of death and an
      important cause of hospital admission and long term disability in Australia.
      Atherosclerotic lesions at the bifurcation of the common carotid artery are the
      most common cause of stroke. On occasion these lesions are partially calcified
      and visible on a conventional panoramic dental radiograph. The atheroma may
      appear either as a nodular radiopaque mass or as two radiopaque vertical lines
      within the soft tissues of the neck at the level of the lower margin of the third
      cervical vertebra (C3). These opacities are separate and distinct from the hyoid
      bone and variably appear above or below it. Dentists should scrupulously review
      the panoramic radiographs of all individuals over age 55 with medical histories
      of hypertension, diabetes mellitus, hypercholesteraemia and coronary artery
      disease, or whose behaviour includes smoking, ethanol abuse, or dietary
      indiscretion coupled with overweight and a sedentary lifestyle which are known to
      be associated with atherosclerosis and stroke.

PMID- 9583229
TI  - Does the public really know what dentists do?

PMID- 9583228
TI  - Fluoride ion concentration in 40 per cent silver fluoride solutions determined by
      ion selective electrode and ion chromatography techniques.

PMID- 9583230
TI  - Paraesthesia following tooth restoration.

PMID- 9583231
TI  - Condylar injuries and post-traumatic ankylosis.

PMID- 9583232
TI  - Paediatric dentistry: avulsion. Case reports.

PMID- 9583233
TI  - An association between a microsatellite polymorphism at the DRD5 gene and the
      liability to substance abuse: pilot study.
AB  - We have conducted a population-based association study of substance abuse and a
      microsatellite at the dopamine D5 receptor locus (DRD5) in a sample of European
      American males and females with substance dependence (SA) or without any
      psychiatric disorder. Overrepresentation of the most frequent allele (148 bp) was
      found in males in the SA group (OR = 2.2, P = .02); this finding was reproduced
      in females (OR = 5.4, p < .001). The difference in the frequencies of this allele
      between SA males and SA females was statistically significant. The genotype coded
      in accordance with the dose of this allele correlated with substance abuse
      liability in males and females (stronger in females) and with novelty seeking in
      females. There was no evidence of correlation between the genotypes of spouses
      that could be induced by assortative mating for the liability to substance abuse.
      The data suggest that the DRD5 locus is involved in the variation and sex
      dimorphism of substance abuse liability.

PMID- 9583234
TI  - Genetic effects on ADHD symptomatology in 7- to 13-year-old twins: results from a
      telephone survey.
AB  - The magnitude of genetic and environmental factors and the influence of contrast
      effects on attention-deficit hyperactivity disorder (ADHD) symptomatology were
      examined on a sample of 900 twin pairs, aged 7-13, participating in the Virginia
      Twin Study of Adolescent Behavioral Development (VTSABD). In addition, the
      genetic and environmental correlations between ADHD and oppositional-defiant
      disorder/conduct disorder (ODD/CD) symptomatology were estimated. A series of
      structural models was applied to maternal ratings from a telephone survey,
      designed to screen for the three dimensions of ADHD symptomatology
      (hyperactivity, impulsivity, and inattention) and ODD/CD symptomatology. Model
      fitting results suggested that ADHD symptomatology is highly heritable and
      influenced mostly by additive genetic, specific environmental, and contrast
      effects. However, this analysis could not exclude with statistical significance
      additional effects from dominance. The results of the best-fitting bivariate
      model suggested that the genetic correlation between the two traits is 50% and
      replicated previous findings of a common genetic factor influencing the
      comorbidity of ADHD and ODD/CD symptomatologies.

PMID- 9583235
TI  - Environmental influences that may precede fertilization: a first examination of
      the prezygotic hypothesis from maternal age influences on twins.
AB  - The prezygotic hypothesis considers the possibility that development is subject
      to environmental influences on the oocyte prior to conception. Such influences
      may occur in the maternal grandmother's uterus where oogenesis is completed or in
      the mother before fertilization. According to this hypothesis, the separate eggs
      from which DZ twins are derived may be sensitive to microenvironmental variations
      within an ovary. As a first approach, we examined same-sex MZ and DZ twins for
      maternal age effects on differences between pairs in cognitive and behavioral
      traits. While no differences between MZ and DZ pairs were found that would
      indicate a major effect of the prezygotic environment, suggestions are made for
      further experimental studies of this unexplored question in human development.

PMID- 9583236
TI  - Longitudinal genetic analysis of menstrual flow, pain, and limitation in a sample
      of Australian twins.
AB  - Genetically informative longitudinal data about menstrual disorders allow us to
      address the extent to which the same genetic risk mechanisms are operating
      throughout the reproductive life cycle. We investigate the relative contributions
      of genes and environment to individual differences in menstrual symptomatology
      reported at two waves, 8 years apart, of a longitudinal Australian twin study.
      Twins were questioned in 1980-1982 and 1988-1990 about levels of menstrual pain,
      flow, and perceived limitation by menses. Longitudinal genetic analysis was based
      on 728 pairs (466 MZ and 262 DZ) who were regularly menstruating at both survey
      waves. A bivariate Cholesky model was fitted to the two-wave data separately for
      flow, pain, and limitation variables. The baseline model comprised common genetic
      and environmental factors influencing responses at both waves and specific
      effects influencing only the second-wave response. We also included age as a
      covariate in the model. Proportions of the longitudinally stable variance in
      menstrual flow, pain, and limitation attributable to genetic and individual
      environmental effects were calculated for the best-fitting models. Genetic
      factors accounted for 39% of the longitudinally stable variation in menstrual
      flow, 55% for pain, and 77% for limitation. The remaining stable variance was due
      to individual environmental factors (61, 45, and 23%, respectively). Therefore
      the stable variance over the 8-year interval was largely environmentally
      influenced for menstrual flow, was approximately equally determined by genetic
      and by nonshared environmental influences in the case of pain, and was due almost
      entirely to genetic influences for limitation by periods. We demonstrate for the
      first time that the same genetic influences are operative throughout the
      reproductive life span.

PMID- 9583237
TI  - Voluntary sodium chloride consumption by mice: differences among five inbred
      strains.
AB  - We examined voluntary NaCl intakes of five mouse strains: NZB/B1NJ, SM/J, 129/J,
      C57BL/6ByJ, and CBA/J. Using two-bottle tests with water as one choice, the mice
      were offered series of progressively increasing or progressively decreasing NaCl
      concentrations (37.5-600 mM NaCl in 48-h tests), then 300 mM NaCl for 6 days and
      75 mM NaCl for 8 days. Low concentrations of NaCl were more avidly accepted by
      mice given the increasing rather than the decreasing series. However,
      irrespective of the test order, test duration, or how the results were expressed
      (i.e., as raw intakes, intakes corrected for body weights, or preferences), the
      NZB/B1NJ mice always had higher NaCl acceptance than did the CBA/J mice. The
      SM/J, 129/J, and C57BL/6ByJ strains were intermediate between the NZB/B1NJ and
      the CBA/J strains, but their distributions varied from concentration to
      concentration. Low (< or = 150 mM) NaCl concentrations were avoided by the
      C57BL/6ByJ and CBA/J mice, but the NZB/B1NJ, SM/J and 129/J mice either preferred
      or were indifferent to them. High (> or = 300 mM) NaCl concentrations were
      strongly avoided by all mice, except for the NZB/B1NJ strain. It is suggested
      that separate genes underlie the strain differences in acceptance of dilute and
      concentrated NaCl solutions.

PMID- 9583238
TI  - Genotypic differences between C57BL/6 and A inbred mice in anxiolytic and
      sedative actions of diazepam.
AB  - The role of genotype in susceptibility to the behavioral actions of
      benzodiazepines is not well characterized. To develop a model for such studies,
      we have characterized the anxiolytic and sedative activities of diazepam in
      C57BL/6J and A/J inbred mice. C57BL/6J mice were more responsive than A/J mice to
      diazepam-induced anxiolytic-like activity in the mirrored chamber aversion assay
      and the elevated plus-maze assay. Basal activity of the two strains did not
      differ in either assay. In contrast, the two strains were equally responsive to
      the anxiolytic effects of the 5-HT1A receptor partial agonist, buspirone.
      C57BL/6J mice were also more susceptible to the sedative effects of diazepam than
      were A/J mice. Flumazenil blocked the effects of diazepam in these behavioral
      assays. Measurement of diazepam and nordiazepam in blood and brain suggested that
      the response differences are of a pharmacodynamic rather than a pharmacokinetic
      nature. Taken together, these findings indicate that C57BL/6J and A/J mice
      provide a valuable tool for behavioral genetic studies of the mechanisms
      underlying the pharmacological actions of benzodiazepines.

PMID- 9583239
TI  - Wing-beat frequency mutants and courtship behavior in Drosophila melanogaster
      males.
AB  - Flightless mutations that affect wing-beat frequency (WBF) of Drosophila
      melanogaster were examined for their effect on male courtship. WBFs were measured
      using a fixed-wire tether that completely supports the fly in an attitude similar
      to hovering flight. The two spontaneous mutations, one of which reduces WBF to
      one-half normal and the other to zero, were placed on an isogenic background and
      were compared to an isogenic wildtype strain and to a genetically heterogeneous
      wildtype strain. Time to mating under noncompetitive conditions (single pair
      matings) was not significantly different among the four male types in one
      experiment. In a second experiment, although the time to mating varied
      significantly among the four male types, there was no association between the WBF
      that was characteristic of a male type and the length of time to mating. Time to
      mating was not significantly correlated with WBF, wing size, or body mass in
      either experiment. Genetically heterogeneous wild-type females were significantly
      more receptive (had shorter times to mating) than inbred wild-type females toward
      all four male types. During the time-to-mating tests, all four male types
      appeared to show typical courtship behaviors. Therefore, the male types were
      compared for possible differences in four components of the male courtship song:
      sine song frequency, interpulse interval, intrapulse frequency (= carrier
      frequency), and wing cycles per pulse. One or another of these components showed
      significant differences among the four male types (e.g., genetically
      heterogeneous, wild-type males showed a significantly higher sine song frequency
      and intrapulse frequency than males of the three isogenic types). However, the
      average values for all four male types were within reported wild-type ranges for
      each courtship song component. Although the two mutations drastically reduce WBF
      during tethered flight, they do not have any similar major effect on courtship.
      Apparently they affect muscles or neuronal control mechanisms that are not common
      elements shared by the wing movement of flight and male courtship song.

PMID- 9583241
TI  - An outbreak of acute rheumatic fever in Nova Scotia.

PMID- 9583240
TI  - Influence of early environment on the circadian period of the tau-mutant hamster.
AB  - The role of the period of the environmental cycle during gestation and infancy on
      the circadian period of adult hamsters was studied. Tau-mutant hamsters of all
      three genotypes (+/+, 24-h circadian period; +/tau, 22-h period; tau/tau, 20-h
      period) were conceived and raised under either a 20-h light-dark cycle or a 24-h
      cycle. The circadian period in constant darkness was determined at 2 months of
      age by inspection of records of running-wheel activity. Differences in circadian
      period of up to 1.2 h were observed. However, changes of the same magnitude were
      also observed in animals conceived and raised under a 24-h cycle and exposed to a
      20-h cycle at 8 months of age. Therefore, it is concluded that the aftereffects
      of entrainment can account for the apparent influence of the early environment.
      The free-running period of the circadian pacemaker seems to be under complete
      genetic control and not to be influenced by the period of the environmental cycle
      under which the animal is raised.

PMID- 9583242
TI  - Epidemic methicillin-resistant Staphylococcus aureus strain--Ontario.

PMID- 9583244
TI  - Hepatitis A in restaurant clientele and staff--Quebec.

PMID- 9583243
TI  - Respiratory virus surveillance. FluWatch project, 1997-1998.

PMID- 9583246
TI  - Principles of authorship in health promotion research.

PMID- 9583245
TI  - Universality: moving beyond access to outcome.

PMID- 9583247
TI  - Sexual health knowledge of students at a high school in Nova Scotia.
AB  - PURPOSE: In the context of a community development project related to adolescent
      sexual health, this study was carried out at Amherst Regional High School (ARHS)
      in Amherst, Nova Scotia, to assess students' sexual health knowledge, gender
      differences in knowledge, and associations between knowledge and sexual
      behaviours. METHODS: A 29-item scale assessed knowledge in five areas of sexual
      health. Gender differences in correct responses to questions were compared.
      Overall knowledge scores were compared by gender, grade, and sexual activity, and
      tested for association with sexual behaviours. RESULTS: Of 796 students, 80%
      participated. Sexual health knowledge scores were highest for sexually active
      females. Higher score was associated with oral contraceptive use and later sexual
      debut. Knowledge was highest for HIV/AIDS. Students were insufficiently aware of
      their right to patient confidentiality. CONCLUSIONS: ARHS students lack knowledge
      in some sexual health areas. School programs should consider these findings, and
      work to improve school-based sexual health education.

PMID- 9583248
TI  - Adolescent sexual behaviour: results from an Ontario sample. Part II: Adolescent
      use of protection.
AB  - This paper reports the frequency of use of protection and rates of birth control
      pill/condom use by age and gender among a large, sexually active group of Ontario
      adolescents who were followed from 12 to 17 years of age. The sample consisted of
      the 759 males and 690 females who reported engaging in sexual intercourse during
      the McMaster Teen Project. Significantly more females aged 15-17 years reported
      always using a method of protection, and using the birth control pill. Condom use
      was more frequent among males at all ages, but reached statistical significance
      at ages 12, 13 and 17 years. Although the numbers reporting no use of protection
      decreased with age, by 17 years 36% of males and 33% of females continued to
      report no use of protection. Large numbers of sexually active Ontario adolescents
      continue to be vulnerable to pregnancy, STDs and AIDS.

PMID- 9583249
TI  - Vaccine coverage during a school-based hepatitis B immunization program.
AB  - Ontario initiated a universal hepatitis B immunization program for grade seven
      students in the fall of 1994. An ecological study was conducted within seven
      health units of the Greater Toronto Area to assess vaccine coverage. The study
      population consisted of all grade seven students enrolled within schools in the
      participating health units, on October 1, 1994. There were 39,935 students
      enrolled in 604 schools eligible for inclusion in the study. Consent to receive
      the vaccine series was obtained for 88% (range across health units from 81.5% to
      96.3%) of the students. Among students for whom consent was obtained, an average
      of 95% (range 88.1% to 99.5%) completed the series. Therefore, the total vaccine
      coverage for the study population was 84% (range 77.5% to 89.5%). Series
      completion varied by school board, education provider and the use of Ministry of
      Health educational material. A limiting factor in achieving high vaccination
      coverage among grade seven students was obtaining consent to receive the vaccine
      series.

PMID- 9583250
TI  - An international comparison of cancer survival: advantage of Toronto's poor over
      the near poor of Detroit.

PMID- 9583251
TI  - Participatory research with native community of Kahnawake creates innovative Code
      of Research Ethics.
AB  - Participatory research requires ethical guidelines to incorporate the needs of
      the partners, i.e., the researchers and the community. This paper describes the
      background, development and implementation of an innovative Code of Research
      Ethics developed for a participatory research project with a Native community in
      Canada. The document ensures that responsibility and control will be shared by
      both researchers and community throughout the project including joint publication
      of the results. It defines community control of data, means of resolving
      dissension at time of publication, incorporation of new researchers and the
      differences between community-based and academic researchers.

PMID- 9583252
TI  - Assessment of postneonatal growth in VLBW infants: selection of growth references
      and age adjustment for prematurity.
AB  - OBJECTIVES: To assess growth outcomes of VLBW infants using different growth
      references and to validate the practice of age adjustment for prematurity in the
      growth assessment for VLBW infants. METHODS: Longitudinal growth data of 514 VLBW
      infants from 4 to 36 months of adjusted age were analyzed separately based on
      chronological and adjusted age and by comparison with three growth references.
      RESULTS: More infants were labelled as having "subnormal growth" assessed on
      chronological age than on adjusted age throughout the first three years of life.
      The proportions of subnormal growth determined using a Canadian and the WHO
      reference for breastfed infants were similar; they were different from those
      obtained using the NCHS/WHO reference. CONCLUSIONS: Our findings suggested that
      the interpretations of growth in VLBW infants vary substantially depending on
      which reference is used. The age adjustment for prematurity makes substantial
      difference in identifying subnormal growth in VLBW infants. The adjustment should
      be carried out throughout the first three years of life.

PMID- 9583253
TI  - Trends and variations in neonatal length of in-hospital stay in Canada.
AB  - PURPOSE: To analyze spatio-temporal variations of neonatal length of in-hospital
      stay in Canada. METHOD: The length of in-hospital stay of 1,469,761 newborns in
      Canadian hospitals from April 1, 1984 to March 31, 1995 recorded by the Canadian
      Institute for Health Information was analyzed. RESULTS: Neonatal length of in
      hospital stay decreased from an average of 5.0 days in 1984 to 2.9 days in 1994.
      In 1994, the average neonatal length of in-hospital stay in Alberta was 2.5 days,
      which was 0.2 to 1.5 days shorter than other provinces. The spatio-temporal
      variations in neonatal length of in-hospital stay could not be explained by
      corresponding variations in birthweight and other neonatal disorders.
      CONCLUSIONS: Neonatal length of in-hospital stay has been substantially reduced
      in Canada in recent years but there remain important interprovincial variations.
      These variations are unlikely to be the results of changes or differences in
      patient-specific factors; policy played an important role.

PMID- 9583254
TI  - Poverty and medical treatment: when public policy compromises accessibility.
AB  - PURPOSE: To explore poor Edmontonians' access to medical treatment services.
      METHODS: Data were collected during interviews with 130 poor Edmontonians.
      RESULTS: 38% of study participants had failed to obtain physician services when
      they were sick or bothered by a health problem, and 40% who had been prescribed a
      medication had not filled the prescription. Participants experienced three main
      barriers to access: lack of money, lack of comprehensive health care coverage,
      and lack of affordable transportation. Findings suggest that a variety of health
      care and social assistance policies limit access to treatment services for people
      living in poor families. CONCLUSION: Despite the principles of the Canada Health
      Act, access to medical treatment is not based solely on need, but is tied, in
      part, to income. There is a need for health care, social, and economic policies
      that aim to reduce the barriers that limit access to physician services and
      prescription medications by people living in poverty.

PMID- 9583255
TI  - [CLSC's Info-Sante: an effective service?].
AB  - Satisfaction, self-care and cost savings resulting from the use of CLSC's Info
      Sante service of the Quebec region have been evaluated in the period 48-72 hours
      after the user's call to the service. Data have been collected by a telephone
      survey on a random sample of 394 users. Results show a very high rate of
      satisfaction with the majority of the 14 selected indicators. The waiting time
      until connection with a nurse was the main source of dissatisfaction.
      Approximately 91% of callers did not have to call back the service for the same
      problem. The majority of users (83%) carried out the actions recommended by the
      nurse, and 89% felt they would be able to handle the problem if it recurred. If
      Info-Sante did not exist, 76% of service users declared that they would have
      visited a doctor to solve their problem. If they had done so, it would have cost
      an estimated nearly two million dollars to the Quebec Government.

PMID- 9583256
TI  - Prevalence of chronic pain.

PMID- 9583257
TI  - Opportunities for a broader understanding of work and health: multiple uses of an
      occupational cohort database.
AB  - Occupational cohort studies conducted to study cancer incidence and mortality
      require extensive data gathering about workers' job histories, exposures, and
      health outcomes. Although this process is expensive, the database created can be
      looked upon as a resource for broad investigations of the relationship between
      work and health. This paper presents the example of a retrospective cohort study
      which began in the traditional way, examining the link between a specific
      pesticide exposure and mortality and cancer incidence. The cohort register has
      since been used to investigate whether infertility, adverse reproductive
      outcomes, and childhood cancers might be associated with this exposure. It is
      also being used as the basis for studying other sawmill exposures including noise
      and wood dust as well as socioeconomic factors including job strain, job
      mobility, unemployment, and retraining. This approach allows both the efficient
      use of occupational cohorts as well as providing the opportunity for
      investigators to develop a more comprehensive perspective on the determinants of
      the health status of workers and their families.

PMID- 9583258
TI  - An ecologic analysis of psychosocial stress and heart disease in British
      Columbia.
AB  - Cardiovascular disease is the leading cause of death in Canada. However, much
      heart disease incidence cannot be explained by known risk factors, and evidence
      points to the potential role played by the psychosocial environment. This study
      involves an ecologic analysis exploring the relationships between psychosocial
      stress and ischaemic heart disease (IHD) in British Columbia. First, data from
      the Canada Health Promotion Survey correlated stress indicators (i.e., education,
      marital status) with self-reported stress levels. Results showed gender
      differences in stress. Stage II consisted of a multivariate analysis of ischaemic
      heart disease mortality in B.C. Results indicate a strong association between
      heart disease outcomes and educational background for both males and females.
      Findings of this study support a link between IHD and psychosocial factors. The
      results of the multiple regression must be interpreted with caution, given the
      use of an ecologic analysis. Additional research at the individual level is
      needed to fully understand these relationships.

PMID- 9583259
TI  - Sexually transmissible diseases surveillance in Australia: towards a coordinated
      national system.
AB  - Communicable diseases surveillance is essential for directing policy development.
      In most regards, sexually transmissible diseases (STD) surveillance is no
      different to surveillance for other communicable diseases. There are nevertheless
      several aspects of STDs that have to be taken into consideration in designing and
      managing surveillance activities. These include particular confidentiality
      concerns associated with STDs, the disproportionate morbidity STDs confer on
      marginalised or stigmatised populations, and clinical limitations due to the
      requirement of often uncomfortable genital examinations for the diagnosis of many
      STDs. Furthermore, interpretation of STD surveillance data requires information
      on sexual behaviour which is not routinely collected for other types of
      surveillance. In addressing new STD surveillance strategies the key public health
      questions that can be answered by surveillance need to be defined. These include
      the prevalence of individual STDs among the total population and specific
      population subgroups, the rates of symptomatic versus asymptomatic disease,
      treatment seeking levels, and antibiotic sensitivity patterns for some agents.
      This article describes possible STD surveillance methodologies to meet these
      demands.

PMID- 9583260
TI  - An outbreak of non-sexually transmitted gonococcal conjunctivitis in Central
      Australia and the Kimberley region.
AB  - From 13 February to 27 June 1997, 447 cases of gonococcal conjunctivitis were
      identified by Communicable Disease and Public Health Centres and Community
      Clinics in the Northern Territory, Western Australia and South Australia. The
      outbreak involved Aboriginal communities predominantly in Central Australia and
      the Kimberley region in Western Australia. This was the first outbreak recorded
      in the Kimberley region. It is not yet known whether the Kimberley cases were
      part of the larger Central Australian outbreak or whether they represented a
      separate and unrelated outbreak. Environmental factors associated with this
      outbreak were similar to those seen in previous outbreaks. Control measures were
      based on early recognition and treatment of index cases and identifying and
      treating contacts. Until sexually transmitted Neisseria gonorrhoeae is controlled
      in communities gonococcal conjunctivitis is likely to appear again. The role of
      oropharyngeal carriage of N. gonorrhoeae needs to be evaluated further.

PMID- 9583262
TI  - Communicable diseases surveillance.

PMID- 9583263
TI  - [Atopic dermatitis--historical and immunological background].

PMID- 9583264
TI  - [Studies on the obesity of Hawaii- and Amami-born Japanese children].
AB  - Carrying out a somatotype comparison of both, by using data of anthropometry of
      Hawaii-born Japanese Children (Hawaii-Children) and Amami-born Japanese Children
      (Amami-Children) that were carried out in 1977-78 a study with regard to the
      determination of obesity was carried out. The result that compared a somatotype
      was as follows. 1. The height of hawaii-Children was almost higher than that of
      Amami-Children. 2. A body weight was almost the same. 3. Trunk length of Amami
      Children was longer than that of Hawaii-Children. 4. Lower limb length of Hawaii
      Children was bigger than that of Amami-Children a little. 5. The letio of Rohrer
      index of Amami-Children was greater than that of Hawaii-Children. Therefore, it
      is determined that Amami-Children were obesity even from Hawaii-Children. when
      obesity index is judged from the ratio of the height to body weight. As for skin
      fold thicknesses (amount of subcutaneous fat), Hawaii-Children is showing a high
      value more always than Amami-Children and Hawaii-Children is obesity obviously.
      Although the measurement result of Rohrer index and skin-fold thicknesses are
      contradicting this cause is because it differs with both trunk length and Lower
      limb length. Considering those result, it became obvious that a obesity index
      calculated from the height and body weight does not show fat volume inside a body
      precisely. The measurement of amount of subcutaneous fat needs to be carried out
      to check real obesity. Also, it is important to carry out the measurement of
      trunk length and Lower limb length in addition to the height and a body weight at
      least, to know a obesity.

PMID- 9583265
TI  - [Studies on the development of fetus scapula].
AB  - Extract and measure the scapular every part from the fetus that was carried into
      Saga medical college, the data was processed statistically. Also, the
      morphological characteristic of scapula of the fetus was clarified by image
      processing that a computer is used. The result was as follows. A scapular
      morphological length and also height become big in proportion to the height of
      fetus. Index of height-length of a fetus was big compared with adult, this trend
      is remarkable especially in a early stage of development of a fetus. Spinal axis
      angle of a fetus was also bigger than that of adult and it remarkable differ from
      an anthropoid very small ane. In general, the scapular shape of a fetus was short
      length with wide-spreading side and this form resembles to scapula of Jomon
      period people. The width of cartilage part tend to decrease as ossification
      progress fast width-wise with growth. However, area of cartilage part tend to
      become big, because the growth of a cartilage part is going fast lengthwise.

PMID- 9583266
TI  - [Changes in the threshold values of lingua throughout aging].
AB  - The filter-paper-disk method was employed for measuring the threshold values of
      four basic taste on lingua-tip with 308 healthy females aged 20-79. Taste
      substance were sequentially diluted with distilluted water (30 stages from 80.0
      g/dl for sucrose, 30 stages from 30.0 g/dl for NaCl, 30 stages from 8.0 g/dl for
      sodium tartrate, 30 stages from 4.0 g/dl for HCl quinine). The result was as
      follows. A sensibility of gustation decreased rapidly in accordance with aging. A
      decrease of bitterness sensibility was most remarkably with aging, succeeded
      sourness, sweetness, saltyness. Also, a decrease of a gustation sensibility is
      beginning in early twenties, especially the sensitivity to a sweetness and sour
      taste decreased conspicuously from twenties to thirties.

PMID- 9583267
TI  - [Self-assessment of vulnerability to illness by the Austrian population].
AB  - Results of a Cross-Sectional Study in 1995: The self-perceived threat of cancer,
      myocardial infarction, stroke, traffic accidents, diabetes mellitus, AIDS,
      Alzheimer's Disease and drug abuse was investigated in a survey among a
      representative sample of Austrians (aged > or = 15 years) in 1995. The most
      feared disease was cancer (41%), followed by traffic accidents (38%) and
      myocardial infarction (36%). The disease feared least was drug abuse (6%).
      Females feared cancer, stroke, diabetes mellitus and Alzheimer's disease
      significantly more than males. A cluster analysis reveals that respondents who
      perceive a higher threat by the diseases have low levels of education and live in
      rural areas. The age distribution of persons who responded with "very
      threatening" corresponds well with the age-specific prevalence of the disease.
      Smoking habits, alcohol consumption and body-mass index have no influence on the
      self-perceived threat of the investigated diseases.

PMID- 9583268
TI  - [Changes in the median life expectancy in free Saxony with reference to age
      specific parameters].
AB  - When analysing an intensified mortality table of the population in Saxony (which
      is situated in central Germany) it became evident that by 1994 in contrast to
      1988 there has been an overall positive development in respect of median life
      expectancy, but it also transpired that this development presented a highly
      differentiated pattern with regard to age-specific parameters among both the
      female and male populations. As far as the female population was concerned,
      social progress resulted in a systematic improvement of survival possibilities in
      childhood and at an advanced age. In the male population there were two age
      brackets (around the 18th year of life and between 32 and 50 years of age) where
      the survival probabilities had still not re-attained the 1988 level. In the
      pensioners' age bracket (starting around the 63rd year of age) the overall
      mortality rate did not attain a lower level compared to 1988. We are at present
      preparing an analysis of this life expectancy pattern with special reference to
      the causes of death.

PMID- 9583270
TI  - [Unemployment as a challenge for general practice].
AB  - Tasks for general practitioners in this field are discussed in connection with a
      two-year follow up of a randomised community sample of 310 unemployed persons in
      Norway. This study supported both the selective and causative mechanisms for
      explaining high morbidity among the unemployed. Thus, medicine is faced with both
      clinical and preventive tasks. Unemployed patients must be cared for by proper
      somatic and/or psychiatric diagnosing. A sociomedical diagnosis of the main
      unemployment problem is suggested. Counselling should be an important part of the
      treatment of unemployed patients. General practitioners may be the only
      independent counsellors of the many possibilities within the social security
      system. Secondary prevention may also be necessary to encourage passive
      unemployed patients to participate in activation programmes offered by the
      community (education, work opportunity programmes, sports, cultural activities,
      etc.). Primary prevention should help to avoid unemployment of more than three
      months' duration. Physicians are encouraged to lobby such measures in their
      communities.

PMID- 9583269
TI  - [Spatial and temporal accessibility of primary health care by the patient--a
      survey in Dresden/Saxony].
AB  - The structural changes in outpatient medical care in eastern Germany took place
      by far-reaching winding up of the outpatient departments. At the same time, many
      doctors from these institutions set up a practice. These changes also concerned
      the medical care by family doctors. It is assumed that as a result of these
      partly extensive changes there are also changes in the accessibility of the
      family doctor by outpatients. We will describe in this paper the level attained
      in Dresden, capital of Saxony in 1995 and 1996, from the point of view of the
      inhabitants. Existing problems are shown. In this connection, random samples of
      inhabitants of Dresden were interviewed by postal survey with questions on this
      subject in 1995 and 1996.

PMID- 9583271
TI  - [Cooperation guidelines--a contribution to the development of process quality in
      psychiatric community management].
AB  - Cooperation in the provision of care to individuals with chronic psychiatric
      illnesses represents a significant criterion for quality. In the Tuebingen
      administrative district, guidelines for cooperation in the handover of patients
      to facilities providing follow-up care and in parallel care of patients have been
      developed. Elements of the guidelines include handover standards, case
      conferences and case management. The results of accompanying research are
      encouraging, while indicating the necessity of continued discussion in the
      individual facilities and in the relevant authorities: The acceptance of the
      guidelines is high and they are considered useful in concrete practice, but
      implementation is sometimes hesitant and the instrument provided for
      documentation is barely used due to time limitations. Only by means of compulsory
      basic documentation will it be possible to evaluate the guidelines and secure the
      criteria for quality on a long-term basis. As with other models, integration of
      neurologists and psychiatrists in private practice into the cooperation with
      inpatient and outpatient facilities is a problem that must yet be resolved.

PMID- 9583272
TI  - [Acceptance of breast feeding and public discussion--evaluation of health
      campaigns for breast feeding between 1991 and 1995].
AB  - In 1990 the Innocenti Declaration on promoting breastfeeding was proclaimed in
      Florence/Italy. It became the subject of resolution 45.34 of the World Health
      Assembly in 1992. In the Federal Republic of Germany there was no wide-scale mass
      media campaign to promote breastfeeding as in other countries. But mother-to
      mother support groups, medical services and the newly founded National
      Breastfeeding Committee supported prolonged breastfeeding in public. The effects
      of the joint effort could be estimated by comparing the results of two postal
      surveys in 1991 and 1995. The surveys were conducted in Lower Saxony, North-Rhine
      Westphalia and Berlin. A tendency could be shown toward more exclusive
      breastfeeding. Breastfeeding with supplementary food increased by a factor of 1.3
      after adjusting for the variables mother's age, sleeping in parents' room or bed
      and no-smoking household. In Lower Saxony the increase was by a factor of 1.5
      starting from a lower base value. The baby sleeping in the parents' room or in
      their bed furthered breastfeeding by a factor of 1.5 to 4. Non smoking mothers
      are 4 times more willing to breastfeed their infants than smoking mothers. German
      mothers breastfeed their infants two to three times more often than turkish
      mothers.

PMID- 9583274
TI  - [Discussion of prerequisites for food production by the public health office-
      section 18 of the Federal Epidemiology Regulation and Section 43 of the Infection
      Control Regulation (draft)].
AB  - The Public Health office of the city of Frankfurt am Main processed from 1994 to
      1995 to total of 13,434 applications for health certificates in accordance with
      section 18 of the Federal Epidemics law. In 78 applicants (= 0.56%) the
      certificate was refused or the applicants barred from exercising their profession
      because of positive findings in their faeces (usually salmonellae). Other
      examining offices had also arrived at clearly less than 1% (0.3-0.6%) positive
      findings. These results support the projected change in the revision of the
      Federal Epidemics law (Law of Protection against Infections) providing for
      omission of the once-only performed examination of faeces, in favour, of an
      intensive and annually repeated training of personnel in matters of hygiene.
      Infection epidemiology data also show that hygiene in the processing of foods of
      animal origin is of prime importance for the incidence of infections caused by
      foods, the other important factor being the ways and means of keeping, breeding
      and producing the animals concerned.

PMID- 9583273
TI  - [Infections with enterohemorrhagic Escherichia coli (EHEC)--results of an
      epidemiologic survey in Bavaria for the April 1996 to May 1997 time frame].
AB  - Using a report system of the Bavarian Public Health services 300 EHEC infections
      were registered within one year (Apr 1, 1996, to Mar 31, 1997) in Bavaria. These
      consisted of 22 cases of haemolytic uraemic syndrome (HUS) (mean age, 2.8 yr), 6
      cases of incomplete HUS (1.3 yr), 188 cases of enteritis (3.3 yr) and 84
      asymptomatic infections (12.9 yr), respectively. From this follows an incidence
      rate for all infections of approximately 2.5 per 100,000 inhabitants and for HUS
      in the age group of children and juveniles up to 18 years of approximately 0.8,
      respectively. Possible sources (paths) of infection registered in relevant
      frequencies were: raw milk consumption (18% of the infected), farm-animal
      associated contact (43%), and contact with patients suffering from diarrhoea
      (36%).

PMID- 9583275
TI  - [Development of public health regulations for tattooing and piercing and their
      realization].
AB  - In the course of prevention of infectious diseases the Public Health office of
      the city of Bremen has made increase efforts to improve hygienic conditions in
      tattoo and piercing studios. Defined and practicable hygienic standards have been
      developed and formulated for and in cooperation with the studios. Supported by
      intense personal counselling of the studios the hygienic standards are now--after
      6-9 months--widely accepted and increasingly observed in practice. This programme
      has been--as a crucial point--supplemented by intense information for the general
      public and the customers of the studios in order to support (and control) the
      practice of hygienic standards in tattooing and piercing also from this point of
      view.

PMID- 9583276
TI  - [Revision of the medical care catalog of mandatory health insurance].

PMID- 9583277
TI  - Effect of adherence on antimicrobial susceptibility of Pseudomonas aeruginosa,
      Serratia marcescens, and Proteus mirabilis.
AB  - A simple method was used for testing the antibiotic susceptibility of adherent
      bacteria to plastic surfaces. Pseudomonas aeruginosa, Serratia marcescens, and
      Proteus mirabilis cells adhering to the bottom of a plastic tissue culture plate
      were incubated in serially diluted antibiotic solutions. After 24-h incubation
      the solutions were removed and a fresh medium without antibiotics was added to
      each well. The viability of the cells was judged by their growth after a further
      24-h incubation. In our assay system, we employed a short incubation time (1-h)
      involving adherence of bacteria to a surface for the purpose of minimizing the
      effect of the glycocalyx on antibiotic activity. Even if the bacteria did not
      form a biofilm, the minimal bactericidal concentrations for adherent bacteria
      (MBCADs) markedly elevated. The MBCADs of ofloxacin well correlated with the
      bacteriological eradication by ofloxacin treatment for urinary tract infections
      (UTIs) associated with indwelling urinary catheters, whereas the minimal
      inhibitory concentrations did not show a correlation. Kinetic studies showed that
      adherent Pseudomonas aeruginosa had a 2 h-lag time before logarithmically growing
      when these bacteria were incubated in Mueller-Hinton broth without antibiotics.
      The tolerance demonstrated by adherent cells is likely to play a role in the
      difficulties encountered in the antimicrobial chemotherapy of biofilm infections.
      Moreover, our assay system was considered to be useful in the therapeutic
      selection of antibiotics for these infections.

PMID- 9583278
TI  - Structural characteristics of Koch's triangle in patients with atrioventricular
      node reentrant tachycardia.
AB  - The aim of this study is to investigate whether patients with atrioventricular
      node reentrant tachycardia (AVNRT) present different structural characteristics
      of Koch's triangle from patients with atrioventricular (AV) reentrant tachycardia
      and other control patients. Fifty-eight patients with arrhythmia or chest pain
      underwent selective coronary sinus angiography so that the diameter of the
      coronary sinus could be measured. The patients with arrhythmia also underwent
      electrophysiological study and measurement of the height of Koch's triangle.
      Patients with AVNRT had large coronary sinus ostial diameters compared with
      patients with AV reentrant tachycardia and those with chest pain (13.6 +/- 2.2 mm
      vs. 10.6 +/- 2.7 mm [p < 0.005] and 10.0 +/- 2.1 mm [p < 0.002], respectively),
      while there were no differences in distal diameter. The ostial diameter in
      patients with dual AV node pathways but noninducible AVNRT (11.8 +/- 1.5 mm)
      tended to be smaller than that in patients with AVNRT. No differences in the
      height of Koch's triangle and electrophysiological characteristics, including AV
      node properties, were found among the study groups. In conclusion, an increased
      size of the coronary sinus ostium (the base of Koch's triangle) is a structural
      characteristic in patients with AVNRT and may be the substrate needed for the
      appearance of AVNRT.

PMID- 9583279
TI  - Proliferative activity, p53 expression and loss of heterozygosity on 3p, 9p and
      17p in atypical adenomatous hyperplasia of the lung.
AB  - We examined the preneoplastic nature of atypical adenomatous hyperplasia (AAH) of
      the lung by comparing the proliferative activity, p53 oncosuppressor gene product
      and loss of heterozygosity (LOH) on 3p, 9p and 17p of 20 AAH lesions (8 cases)
      with corresponding normal peripheral lung tissue and adenocarcinoma from the same
      cases. Analysis of proliferative activity with the Ki-67 labelling index and
      argyrophilic nucleolar organizer regions (AgNORs) score indicated that AAH had a
      proliferative activity intermediate between that of normal cell and
      adenocarcinoma. Although low level expression of p53 was detected in 7 AAH
      lesions, the intensity of p53 expression in AAH was weaker than that in
      carcinomas. Microsatellite analysis of chromosome 3p, 9p and 17p showed LOH of
      18%, 13% and 6% respectively in the AAH lesions, while the corresponding
      carcinomatous lesions showed LOH of 67%, 50% and 17% respectively. All AAH
      lesions that showed LOH had moderate or severe histological atypia. One AAH
      lesion with moderate atypia showed LOH both on 3p and 17p. In conclusion, these
      results indicated that AAH lesions with moderate or severe atypia may show the
      preneoplastic stage of lung adenocarcinoma.

PMID- 9583280
TI  - Hyperparathyroid crisis in a patient with a giant brown tumor of the iliac bone:
      a case report.
AB  - We observed a patient with a giant brown tumor of the iliac bone due to
      hyperparathyroidism. There was a risk of pathologic fracture due to huge cysts
      produced by bone absorption. In hyperparathyroid crisis, control of severe
      hypercalcemia is difficult without resection of the parathyroid gland.

PMID- 9583281
TI  - Living related partial liver transplantation for primary biliary cirrhosis--a
      case report.
AB  - An adult living related partial liver transplantation was performed on a 49 year
      old female with terminal hepatic failure due to primary biliary cirrhosis (PBC).
      The donor was her 53 year-old sister. A sufficient volume of graft tissue was
      obtained, which comprised 1.5% of the body weight of the recipient. The recipient
      had an excellent recovery without any major complications, and was discharged 35
      days after the operation. At 15 months after the operation, the patient has shown
      no signs of rejection while using FK506 and prednisolone as immunosuppressants.
      The progression of symptomatic PBC can be predicted, and the timing of the
      transplantation can be easily determined. In addition, the results of liver
      transplantation for PBC are good. Therefore, adult living related partial liver
      transplantation is an excellent treatment for primary biliary cirrhosis.

PMID- 9583282
TI  - Hormone replacement therapy in postmenopausal women: emerging hope for future.

PMID- 9583283
TI  - The concept and potentials of cardiovascular gene therapy.

PMID- 9583284
TI  - Comparison of in-hospital and follow-up results of directional atherectomy and
      stenting for ostial lesions of the left anterior descending coronary artery.
AB  - Lesions at the ostium of the left anterior descending coronary artery constitute
      a distinct group because of suboptimal results and higher restenosis rate after
      balloon angioplasty. Several non-balloon devices have been used to improve the
      outcome of dilatation of such lesions. We retrospectively compared the in
      hospital and follow-up results of directional coronary artherectomy and stents
      for the treatment of ostial lesions of the left anterior descending artery. Out
      of 37 patients, 12 underwent directional coronary atherectomy and 25, stent
      implantation. The two strategies were deployed at different periods over the past
      five years. The baseline clinical and angiographic characteristics were
      comparable in the two groups. Directional coronary atherectomy was done using 7Fr
      atherocath with adjunctive balloon angioplasty in all. All the stents were
      deployed using moderate to high pressure balloon inflation after adequate
      predilatation. While the pre-procedure luminal diameter stenosis was similar in
      the two groups (87.3 +/- 8.8% vs 89.3 +/- 7.2%; p = NS), the residual stenosis
      was significantly lower in the stent group (5 +/- 2.8%) compared to directional
      coronary atherectomy (18.7 +/- 9.8; p = 0.02). There was no significant
      difference in the primary success rate between the two devices (91.6% directional
      coronary atherectomy vs 100% stent; p = NS). One patient in the directional
      coronary atherectomy group developed acute closure followed by emergency coronary
      artery bypass graft surgery and death. No major complication was observed in the
      stent group. Over a mean follow-up of 9.9 +/- 11.6 months following directional
      coronary atherectomy and 8.6 +/- 4.4 months after stenting, significantly higher
      number of patients (60%) developed recurrence of angina or any event following
      directional coronary atherectomy compared to stent (15.8%; p < 0.02). There was
      no myocardial infarction, coronary artery bypass graft surgery or death in either
      group on follow-up. The need for target lesion revascularisation was
      significantly higher in the directional coronary atherectomy group (50%) compared
      to stenting (10.5%; p < 0.02). Comparing directional coronary atherectomy with
      stent, the event-free survival was 80 percent vs 94.7 percent at three months and
      50 percent vs 84.7 percent, both at six and nine months, respectively. In
      conclusion, stenting of the left anterior descending artery ostial lesion results
      in a significantly lesser post-procedure residual stenosis, improved in-hospital
      outcome, a lesser need for target lesion revascularisation and much improved
      event-free survival on follow-up as compared to directional coronary atherectomy.
      Therefore, stenting appears to be a more favourable treatment option compared to
      directional coronary atherectomy for the treatment of ostial lesions in the left
      anterior descending artery.

PMID- 9583285
TI  - Clinical evaluation of new balloon mountable coil stent: in-hospital and follow
      up results.
AB  - The purpose of this study was to determine the feasibility, safety and efficacy
      of elective deployment of a new coil-stent (KR stent) in patients with coronary
      artery disease. KR stent deployment was attempted in 100 patients (135 lesions)
      enrolled prospectively at a single centre from December 1996 to March 1997. Ten,
      15, 18, 24, and 32 mm long KR stents were manually crimped onto balloons and
      deployed in native coronary artery lesions. Majority of the patients had recent
      acute coronary syndromes (unstable angina 30% and post-myocardial infarction
      angina 56%). Diabetes was present in 34 percent of the patients. Fifty-six
      percent had single-vessel and 44 percent multi-vessel disease. In 38 percent, the
      lesions were located in proximal segments and 40 percent of lesions were long. KR
      stents were successfully deployed in 98 percent of patients. Mean minimal luminal
      diameter increased by 2.89 +/- 0.63 mm (from 0.57 +/- 0.38 mm before to 3.45 +/-
      0.56 mm after the procedure). Mean percent diameter stenosis decreased from 83.33
      +/- 10.84 percent before to 3.38 +/- 5.74 percent after the stent deployment.
      Mean reference vessel diameter was 3.45 +/- 0.56 mm. There were occasional
      technical complications including balloon rupture (1), stent migration (2) and
      distal embolisation of atheromatous material (1). One patient developed subacute
      stent thrombosis. There were no other major in-hospital cardiovascular events. At
      the end of six-month follow-up, there were no myocardial infarction or death. Six
      patients presented with recurrence of symptoms within six-months of the
      procedure, four of whom underwent target vessel revascularisation procedure. In
      conclusion, the in-hospital and six-month follow-up clinical results were highly
      encouraging with KR stent. Successful deployment rates were high despite
      unfavourable clinical and angiographic background. Low clinical events on follow
      up will make it suitable for elective stenting.

PMID- 9583286
TI  - Plasma fibrinogen--an independent risk factor for ischaemic heart disease.
AB  - Although several risk factors have been identified for ischaemic heart disease,
      yet their predictive value on an individual basis remains rather low. Hence there
      is a need to identify other variables that can be associated with ischaemic heart
      disease. Fibrinogen level has been associated as an independent risk factor in
      studies undertaken in the west. This study was done to find out whether
      fibrinogen level is a risk factor in Indian populations. Out of 131 consecutive
      male subjects undergoing coronary angiogram over a four-month period, 98 were
      found to have ischaemic heart disease based on angiogram. Fibrinogen levels
      (estimated using the Clauss method) were higher in patients with ischaemic heart
      disease when compared with controls (374 +/- 11.9 vs 268 +/- 14.9 p < 0.0001). In
      the multivariate analysis it was found that fibrinogen levels more than 300 mg
      percent had an odds ratio of 4.4 for ischaemic heart disease (confidence interval
      of 2.4 to 19). The only other variable associated with ischaemic heart disease
      other than fibrinogen, was low level of HDL. The fibrinogen levels were higher in
      patients with triple-vessel disease when compared with single or two-vessel
      disease. Our results are in agreement with the findings in the west that
      fibrinogen levels are a risk factor for ischaemic heart disease. This factor
      needs to be addressed seriously and steps taken to lower the fibrinogen level in
      clinical practice.

PMID- 9583287
TI  - Hyperinsulinemia in non-obese, non-diabetic subjects with isolated systolic
      hypertension.
AB  - To investigate the inter-relationship of hyperinsulinemia and isolated systolic
      hypertension, 15 patients with isolated systolic hypertension (Group I) were
      compared to those having systolic and diastolic hypertension (Group II), and 14
      age- and sex-matched controls (Group III). Significantly high triglycerides and
      total cholesterol were observed in Groups I and II (p < 0.001) and low high
      density lipoprotein cholesterol in Group II (p < 0.001), when compared to
      controls. Significantly high number of patients had impaired glucose tolerance
      (80%; p = 0.0002 and 60%; p = 0.05) on oral glucose tolerance test in Groups I
      and II, respectively. Higher blood glucose values were observed in Group I as
      compared to Group III, at 0, 30, 60 (p < 0.05) and 120 minutes (p < 0.001).
      Subjects in all the three groups showed fasting normo-insulinemia. At 60 minutes
      during oral glucose tolerance test, higher insulin levels were seen in Groups I
      and II as compared to controls (p = NS). Peak insulin levels and area under curve
      for insulin were higher in Groups I and II as compared to controls (p = NS). The
      observations of the present study indicate that, similar to systolic and
      diastolic hypertension, several features of insulin resistance syndrome such as
      hyperinsulinemia, dyslipidemia and glucose intolerance accompany isolated
      systolic hypertension.

PMID- 9583288
TI  - Evaluation of cardiac symptoms by trans-telephonic electro-cardiographic
      monitoring (TTEM): preliminary experience.
AB  - Between May 1996 and May 1997, a total of 398 patients (321 males, 77 females)
      were registered at our institute for trans-telephonic electro-cardiographic
      monitoring (TTEM). Their age ranged from one month to 95 years. Almost two-third
      (67%) of patients were from Delhi and one-third (33%) from other places in India
      and neighbouring countries. Clinical profile of these patients was post-bypass
      surgery, post-myocardial infarction, chest pain for evaluation, post-percutaneous
      transluminal coronary angioplasty, chronic stable angina, evaluation of
      palpitations, arrhythmias, and pace-maker follow-up. Out of 664 symptomatic
      transmissions, 568 (86%) were received for cardiac symptoms and 96 (14%) for non
      cardiac symptoms. Seventy-nine percent patients had chest pain or palpitations at
      the time of transmission, whereas 21 percent had other symptoms like chest
      discomfort, breathlessness or dizziness. The electro-cardiograms were transmitted
      within one hour of the onset of chest pain in 84 percent, palpitations in 78
      percent and dizziness in 75 percent. Of patients with symptomatic transmissions,
      628 (95%) required either reassurance or drug-dose adjustment and outpatient
      department review. Only 36 (5%) patients were hospitalised as an emergency, and
      out of these only 19 (3%) needed acute management. In conclusion, trans
      telephonic electro-cardiographic monitoring is a very convenient and an 'all-time
      available' monitoring facility for establishing patient-physician contact in the
      shortest time. It is useful in rendering instant advice for hospitalisation in
      emergency situations while avoiding unnecessary visits to the hospital.

PMID- 9583289
TI  - L-carnitine in children with idiopathic dilated cardiomyopathy.
AB  - L-carnitine has been used in dilated cardiomyopathy secondary to carnitine
      deficiency in children, with favourable results. There are no reports on the
      effects of L-carnitine in children with idiopathic dilated cardiomyopathy. We
      undertook a prospective study to evaluate the effects of L-carnitine in children
      with idiopathic dilated cardiomyopathy. Thirteen children, mean age 3.29 +/- 1.44
      years, with idiopathic dilated cardiomyopathy underwent echocardiographic
      evaluation while on conventional treatment alone, and with additional L-carnitine
      (50 mg/kg/day). To obviate the effects of spontaneous improvement, eight patients
      (Group 1) were restudied three weeks after stopping the drug, and five (Group 2)
      were restudied three weeks after addition of carnitine. Conventional treatment
      was continued throughout. After repeat echocardiographic examination, the
      parameters were compared statistically. With addition of carnitine, besides
      symptomatic improvement, the mean left ventricular ejection fraction improved
      from 36.9 +/- 16.1 percent to 46.9 +/- 14.5 percent (p < 0.001) and the mean pre
      ejection period/left ventricular ejection time ratio from 39.07 +/- 14.8 to 43.2
      +/- 8.1 (p < 0.01) in the entire group. These changes were concordant in both the
      subgroups. It was concluded that L-carnitine therapy in children with idiopathic
      dilated cardiomyopathy led to modest improvement in left ventricular function.

PMID- 9583290
TI  - Aortic dissections: a pathologic study of 35 autopsied cases.
AB  - A study of 35 autopsied cases of aortic dissection collected over a period of 12
      years was carried out. There were 25 males and 10 females, and the majority of
      the dissections presented in fourth to fifth decade of life. Thirty-six
      dissections were present in 35 cases. Type III was the commonest (50.0%),
      followed by Type I (41.7%) and Type II (8.3%) dissections. Rupture following
      acute dissection was the cause of death in 15 patients. In chronic types, the
      causes of death were not related to dissection. Hypertension, connective tissue
      disorders and trauma were identified as some of the risk factors.

PMID- 9583291
TI  - Effect of endothelial cells on the lymphoproliferative response in Takayasu's
      arteritis.
AB  - Takayasu's arteritis, also known as 'non-specific aortoarteritis' is an
      inflammatory disease of the aorta and its major branches. It also involves the
      pulmonary artery. The aetiology of the disease is not known so far. Abnormalities
      of the endothelial cells in terms of their structure and function are seen in the
      pathology of a number of diseases affecting the blood vessel wall. However,
      involvement of the endothelial cells in non-specific aortoarteritis is not known.
      In an effort to identify the role of endothelial cells in the pathogenesis of
      Takayasu's arteritis, peripheral blood lymphocytes isolated from the blood of
      patients suffering from Takayasu's arteritis were cultured in the presence of
      endothelial cells alone and in the presence of mitogens concanavalin-A and
      phytohaemagglutinin-P. The peripheral blood lymphocytes of patients with
      Takayasu's arteritis showed a significantly decreased blastogenic response to the
      mitogen concanavalin-A when cultured in the presence of endothelial cells. Our
      result thus suggests that endothelial cells may probably induce an inhibitory
      effect on the lymphocytes in patients with Takayasu's arteritis.

PMID- 9583292
TI  - Myocarditis simulating acute myocardial infarction in an adolescent boy.

PMID- 9583293
TI  - Mucormycosis of the heart presenting as paraparesis.

PMID- 9583294
TI  - Anomalous origin of left anterior descending coronary artery from pulmonary
      artery in addition to anomalous origin of left circumflex coronary artery from
      right aortic sinus--a case report.

PMID- 9583296
TI  - Diagnosis of proximal interruption of right pulmonary artery by transoesophageal
      echocardiography.

PMID- 9583295
TI  - Anomalous origin of the left coronary artery from the right sinus of valsalva.

PMID- 9583297
TI  - Anterior mitral leaflet aneurysm--a case report.

PMID- 9583298
TI  - Antemortem diagnosis of cardiac tuberculoma.

PMID- 9583299
TI  - Non-surgical mitral commissurotomy using metallic commissurotome.
AB  - Percutaneous transatrial mitral commissurotomy using a new miniaturised metallic
      commissurotome mounted on a 12 F catheter was done in 24 patients with severe
      mitral stenosis. There were 17 (70.8%) females and seven (29.2%) males with age
      ranging from 12-42 years (mean 26.0 +/- 6.7 years). Atrial fibrillation was
      present in three (12.5%) patients. Three (12.5%) patients had restenosis
      following closed mitral commissurotomy. The mitral valve score on
      echocardiography ranged from 6 to 10 (mean 7 +/- 1.3). The procedure was
      performed with one device which was reused after sterilisation with
      glutaraldehyde. The device was opened maximally upto 39.0 +/- 1.7 mm (range 35-40
      mm). The procedure was successful in 23 (95.8%) patients. The mean left atrial
      pressure decreased from 26.8 +/- 8.0 to 9.3 +/- 7.1 mm Hg (p < 0.001). There was
      a fall of mean pulmonary artery pressure from 47.2 +/- 18.6 (range 20-29 mm Hg)
      to 23.6 +/- 9.6 mm Hg (range 12-51 mm Hg) (p < 0.001). The mitral valve area as
      assessed by Doppler echocardiography (pressure half time) increased from 0.9 +/-
      0.1 (range 0.6-1.2 cm2) to 2.1 +/- 0.4 cm2 (range 1.6-2.6 cm2) (p < 0.001), with
      split in both commissures in 22 (95.6%) cases. One patient developed severe
      mitral regurgitation with tear in the anterior mitral leaflet needing immediate
      mitral valve replacement. One patient developed transient aphasia which recovered
      completely within four hours. Percutaneous transatrial mitral commissurotomy
      using metallic commissurotome offers reliable and effective alternative to
      balloon mitral commissurotomy and may be more cost-effective because of its
      reusability.

PMID- 9583300
TI  - Is the estimation of mitral valve area a sine qua non in the echo-Doppler
      evaluation of mitral stenosis?

PMID- 9583301
TI  - Non-coronary cardiac interventions. The second report of the Non-Coronary Cardiac
      Intervention Registry, the Cardiological Society of India.

PMID- 9583303
TI  - Predicting the hazards of whole-body vibration--considerations of a standard.
AB  - International Standard 2631 (1997) is concerned with the standardisation of the
      measurement, evaluation and assessment of whole-body vibration. With respect to
      health effects of whole-body vibration, the standard offers a combination of
      alternative methods so that different conclusions can be reached according to
      what is measured, how it is evaluated and how it is assessed. Various matters
      requiring consideration during a revision of the standard are suggested. The
      guidance for assessing the severity of whole-body vibration in ISO 2631 (1997) is
      compared with equivalent guidance for assessing hand-transmitted vibration in ISO
      5349 (1986). It is suggested that when revising these standards some
      consideration should be given to the apparent contradictions suggesting that some
      exposures to whole-body vibration may be acceptable even though the same
      conditions would be considered unacceptable for hand-transmitted vibration.

PMID- 9583302
TI  - Coronary artery disease in South Asians. Second meeting of the International
      Working Group. 16 March 1997, Anaheim, California.

PMID- 9583304
TI  - Whole-body vibration suppresses gastric motility in healthy men.
AB  - The influence of whole-body vibration on gastric motility was investigated by
      using an electrogastrography (EGG) in seven healthy men. The EGG is usually
      referred to as a noninvasive technique of recording gastric myoelectrical
      activity by means of placing electrodes on the abdominal surface. Sinusoidal
      vertical vibration at each of 3 different frequencies (10 Hz, 20 Hz, 40 Hz) were
      randomly given to the subject seated on a platform of vibrator for 5 min. The
      vibration magnitude was kept at a constant of 2.0 msec-2 (r.m.s.) during
      operation. The mean dominant frequency of EGG at control period was prior to
      operation 3.3 cycles per min (cpm). During vibration exposure at 10 Hz, the peak
      of dominant frequency increased to 3.9 cpm, and the relative power of slow wave
      showed the statistically significant decrease (45.8%, p < 0.05). The mean
      relative power of slow wave which is composed of frequencies ranged from 2.0 to
      5.0 cpm was 56.6% at control period. On the contrary the mean relative power of
      frequencies ranging from 5.0 to 9.0 cpm, tachygastria increased from 29.5% to
      39.1%. These results suggest that the short-term exposure to whole-body vibration
      effects on the gastric myoelectrical activity.

PMID- 9583305
TI  - Momentary discomfort caused by vibration of railway vehicle.
AB  - When trains pass level crossings or turnouts, they are momentarily subject to
      relatively strong vibrations. In railway engineering, evaluation of the riding
      comfort under such occasional vibrations is called the momentary evaluation,
      which is distinguished from the long-term evaluation. In order to identify the
      effective vibrational characteristics on the momentary evaluation now
      controversial in Japan, an experiment was performed with a riding comfort
      simulator. Twenty adult subjects were exposed to lateral vibration with varying
      peak acceleration and crest factor. Referring to the vibrations of real trains,
      the peak acceleration in the range of 0.35-2.00 m/s2 were varied in steps of 0.35
      m/s2 and the crest factors in the range of 1.5-5.0 were varied in steps of 0.5.
      The frequency was set constant at 2 Hz. The task was to rate the degree of
      discomfort under each vibration which was given them successively. Results
      indicate that changes in the peak acceleration are most effective, and
      application of the crest factor in parallel improves the correlation with the
      perceived discomfort. Whether subjects can perceive changes in the peak or not
      affects the evaluation. Weights of vibrational characteristics that make a cue to
      the evaluation by subjects differ from person to person.

PMID- 9583306
TI  - The effect of backrest angles on discomfort caused by fore-and-aft back
      vibration.
AB  - The effect on discomfort of the frequency and the backrest angle of x-axis (fore
      and-aft) vibration of backrest have been studied. The method of adjustment was
      employed to obtain contours of equivalent comfort for three types of rigid
      backrests, whose surface were vertical, inclined 20 degrees and 40 degrees from
      vertical. Eighteen subjects were required to adjust test vibration over the
      frequency range 2-80 Hz to produce discomfort equivalent to that caused by 10 Hz
      0.25 m/s2 r.m.s. sinusoidal reference vibration for each backrest. The direction
      of vibration was perpendicular to backrest surface. Results shows that the
      sensitivity at 20 and 40 Hz on inclined backrests is significantly about 1.4 to
      1.5 times greater than that on a vertical backrest (p < 0.01) but there is no
      significant difference between the two contours for inclined backrests. The
      contour for a 'vertical' backrest obtained in this experiment agrees with the
      contour calculated from the frequency weighting factors for x-axis back
      vibration, Wc, in ISO2631-1, but the contours for inclined backrests do not agree
      with the contour well.

PMID- 9583307
TI  - Experimental studies of subjective response to road traffic-induced building
      vibration.
AB  - The road traffic-induced building vibration was recorded continuously for 24 hr
      in three orthogonal axes outside and inside the building. Several alternative
      objective methods of quantifying the severity of exposures to whole-body road
      traffic-induced building vibration are used. The relationship between the results
      of all objective evaluation methods of vibration-induced by road traffic and the
      subjective responses to building vibration are compared. It was conducted that
      the ISO 2631-2 z-axis frequency weighting combined with a measure of vibration
      dose value (VDV = [integral of a4(t) dt)]1/4 may use a practicable objective
      evaluation procedure in buildings than L10 percentile vibration levels. It was
      also cleared that the L10 percentile vibration levels at the ground boundary of
      the regulation law of Japan Environmental Agency must be low levels.

PMID- 9583308
TI  - Evaluation of whole-body road traffic vibration in building.
AB  - Level fluctuating vibration has been evaluated by the cumulative index L10, but
      some investigators suggest that the L10 cannot represent an adverse comment on
      vibration. In order to clarify the compliant, various factors involving vibration
      need to be analysed together by statistical methods, for instance factor analysis
      or quantum theory. The authors investigated the relationship between an
      evaluation index and human sensation of vibration in a subjective experiment in a
      wooden house. The subjects were exposed to vertical road traffic vibration
      reproduced with an electrodynamic vibrator placed near the house. The range of
      vibration levels at surfaces in contact with the subjects were from 50dB to 70dB
      in root mean square of frequency weighted acceleration level, i.e. the vibration
      level. Numbers assigned by the subjects and evaluation indices of the vibration
      level were analysed by applying the Stevens power law. The results showed that
      L10 or Leq (55) could become an effective index for the assessment of subjective
      perception of level fluctuating vibration in a wooden house.

PMID- 9583309
TI  - Whole-body vibration and health effects in the agricultural machinery drivers.
AB  - Recently farm mechanization has been widespread and developing rapidly, in
      particular riding farm machines are increasingly used in paddy fields in Japan.
      We have no information available on the actual situation regarding whole-body
      vibration on the seats of these farm machines from the standpoint of labour
      protection. Measurement and evaluation of whole-body vibration was performed on
      the seats of popular riding agricultural machineries. Whole-body vibration on the
      seats of combine harvesters and wheel tractors exceeded exposure limits and the
      fatigue-decreased proficiency boundary limit of 8 hr and also shortened the
      reduced comfort boundary limits of ISO 2631 (1985). Some combines, tractors and
      carieers had only less than one hour exposure duration as compared with the ISO
      2631-1 standard (1997). On the other hand a questionnaire was also performed on
      the subject of agricultural machine operators. Any specific injury or other
      effects, i.e. low back injuries were not found among the group of operators as
      compared with those in non-operator farmers. It seems to be difficult to find out
      the health effects of whole-body vibration itself, because there may be a lot of
      causes, i.e. working posture, operating heavy materials, in farm working
      conditions.

PMID- 9583310
TI  - Development of vibration protection seats for agricultural machinery.
AB  - Seats have been newly developed with an anti-vibration suspension system for
      agricultural machinery. These seats were examined in a series of laboratory tests
      to determine their static and dynamic physical characteristics. These seats are
      specifically designed for the Japanese physique. An artificial track was
      constructed to simulate a farm field based on BSI (British Standard) and to
      examine vibration the transmissibility of the seats when installed in machinery.
      The results indicated that the transmissibility from under the seat to on the
      seat in the vertical direction was approximately 0.25, although little reduction
      of vibration was observed in the fore-aft direction. This suggests that these
      seats are applicable to the agricultural field.

PMID- 9583311
TI  - Prevention strategy for vibration hazards by portable power tools, national
      forest model of comprehensive prevention system in Japan.
AB  - In the 1950s, the introduction of portable power tools into the production
      process of many industries began on a large scale around the world and resulted
      in many cases of occupational vibration syndrome after the 1960s. There was an
      urgent world wide need to undertake preventive steps, medical assessment and
      therapy. At the end of 1964, our investigation began in Japanese national
      forests, and then in mines and stone quarries. The Japanese Association of
      Industrial Hygiene established a "Committee for Local Vibration Hazards" (1965),
      and many researchers in the medical and technological fields joined this
      Committee. After 10 years, a comprehensive system for the prevention of vibration
      syndrome was established in the national forestry. It consists of 1) improvements
      in vibrating tools, 2) hygienic regulation of operation time with an alternative
      working system, 3) health care system involving early medical checks, early
      therapy and age limitations in operation of vibrating tools, 4) protection
      against cold in the workplace and while commuting, and 5) education and training
      for health and safety. The prevention strategy for vibration syndrome in our
      national forests is to establish a comprehensive prevention system in cooperation
      among researchers in the medical and technological fields, workers and
      administration. The Ministry of Labor presented that strategy as good model of
      prevention for other industries (1976). New designs for this model were developed
      and adapted according to the special conditions of each industry. Thus
      comprehensive system for prevention of vibration syndrome developed successfully
      from the late 1970s to 1980s in Japan.

PMID- 9583312
TI  - Affected segments of the median nerve detected by fractionated nerve conduction
      measurement in vibration-induced neuropathy.
AB  - Peripheral neuropathy in the hand has often been reported in workers using hand
      held vibrating tools. But the affected location in the hand is not clearly
      demonstrated. To elucidate the impaired segment of the median nerve within the
      hand, fractionated median sensory nerve conduction velocity (SCV) was measured in
      the digital, finger-to-palm, palm-to-wrist and wrist-to-elbow segments. Subjects
      were 56 patients with hand-arm vibration syndrome and 43 healthy controls of
      similar age. SCV in the digital and the wrist-to-palm segments was significantly
      slower in the patients than the controls. Slowed SCV in the digital segment was
      encountered in 36% of the patients, while the slowing in SCV in the wrist-to-palm
      segment (across the carpal tunnel) was found in 20% of them. The slowing in the
      digital segment was more frequently encountered in the advanced stage of the
      Stockholm sensorineural (SN) stage for hand-arm vibration syndrome: 10% in 0SN
      (no neurological symptoms) while 56% in 3SN (severe stage). The present study has
      demonstrated that vibration-induced nerve impairments dominantly exist both in
      the digits and across the carpal tunnel. Careful neurophysiological assessment is
      important to confirm the impaired location within the hand.

PMID- 9583313
TI  - Health surveillance of forestry workers exposed to hand-arm vibration in Wakayama
      from 1974 to 1996.
AB  - To clarify the trends in the number and the severity of vibration syndrome in
      Wakayama for these 23 years, the records of the medical examinations for
      vibration syndrome were analyzed with 4,652 (a total of 9,920) private forestry
      workers exposed to hand-arm vibration. The number of the subjects who took the
      medical examinations reached a maximum of 1,242 in 1978. After that, it decreased
      year by year, but remained at about 300 or less from 1988. There was a
      corresponding increase in age and the number of years of operating chain saws
      among the subjects examined. The compensated cases reached a maximum number of
      393 cases in 1977, and then a drastic decrease was noted. Year by year there was
      an increase in the number of cases whose medical examinations revealed no
      abnormality. The regional occupational health care system including the
      surveillance card, which has been active since 1975, has probably contributed to
      the decrease or prevention of occurrence of vibration syndrome in Wakayama.

PMID- 9583314
TI  - Effects of room temperature, seasonal condition and food intake on finger skin
      temperature during cold exposure test for diagnosing hand-arm vibration syndrome.
AB  - For diagnosing the hand-arm vibration syndrome, peripheral circulation and
      sensory tests immersing one hand in cold water at 10 degrees C for 10 min have
      been performed widely in Japan. The authors investigated the effects of room
      temperature, seasonal condition and food intake on the test results, especially
      finger skin temperature. Six healthy males were examined repeatedly under six
      different room temperatures at 10 degrees C, 15 degrees C, 20 degrees C, 22.5
      degrees C, 25 degrees C and 30 degrees C. Eight healthy males were examined under
      room temperatures at 10 degrees C, 20 degrees C and 30 degrees C, repeatedly in
      winter, spring, summer and autumn. Six healthy males were examined in summer
      under room temperature at 22.5 degrees C repeatedly 1 hr after, 3 hr after meal
      and after fasting for 13 hr. The finger skin temperature was strongly affected by
      room temperature. The finger skin temperature was also affected by seasonal
      condition. No remarkable effect of food intake was observed. For estimating
      circulatory function of the upper extremities using the finger skin temperature,
      the room temperature should be strictly controlled and the effect of seasonal
      condition must be taken into consideration.

PMID- 9583315
TI  - Finger skin temperature and laser-Doppler finger blood flow in subjects exposed
      to hand-arm vibration.
AB  - OBJECTIVES: This study was aimed to assess the peripheral circulatory functions
      of forestry workers exposed to hand-arm vibration, using simultaneous
      measurements of finger skin temperature (FST) and finger blood flow (FBF).
      METHODS: The subjects were five men with vibration-induced white finger (VWF),
      four subjects with numbness in their hands and five exposed controls without any
      signs or symptoms related to vibration syndrome. Simultaneous measurements of FST
      and laser-Doppler FBF were performed before, during and following a 10-min
      recovery period after the hand was immersed in cold water (10 degrees C, 10 min).
      Partitional measurements of finger blood flows could be made between the
      capillaries and deeply located vessels using two laser-Doppler flow probes having
      narrower and wider optic fiber separations. RESULTS: The FST as well as the FBF
      of the capillary and deeply located vessels during and following the cold
      immersion test in those with VWF and in the subjects with numbness had a slight
      increase immediately following the cold immersion and no tendency to be augmented
      as the time span increased. After the cold immersion test, the control group had
      significantly greater FST and FBF compared to other groups. Particularly, from
      the 5th to the 10th min after the cold provocation, the values of FBF of the
      deeply located vessels in those with VWF were significantly lower than the
      controls. During the course of observation, the FST had significantly linear
      relationship with the recorded capillary and deep FBF values, and that was much
      closely correlated with the deep FBF (i.e., P < 0.01 in each selected condition).
      The slope of the regression lines in the capillary were steeper and shallow in
      the deep FBF. CONCLUSIONS: In addition to the measurement of capillary FBF, more
      detailed and accurate information on the peripheral circulatory functions of
      vibration-exposed subjects can be obtained by including the assessment of the
      deep FBF.

PMID- 9583316
TI  - Measurement of hand-transmitted vibration of tapping the long cane for visually
      handicapped people in Japan.
AB  - The long cane can be used as a mobility aid for visually handicapped people.
      According to a questionnaire completed by Japanese cane users, it seems they are
      not always satisfied with using long canes for a variety of reasons. In this
      study, hand-transmitted vibration from the long cane due to tapping the ground
      was measured because an exposure to repeated shock-type tapping vibration may
      affect the hand-arm system. A sighted female wearing a blindfold participated.
      The measurement was carried out in different conditions with three different
      ground materials both indoor and outdoors. The vibration at three axes of the
      cane grip and one axis at the wrist were measured. The pinch forces between an
      index finger and the grip were also measured using a strain gauge in order to
      observe how the vibration characteristics depend on the changing forces.
      Measurement, evaluation and assessment were based on the International Standard
      (ISO 5349). The estimated daily exposure time and the transmissibility were
      obtained in order to investigate the severity of the hand-transmitted vibration
      caused by the long cane. It was found that the characteristics of tapping
      vibration depend on different measurement conditions and the vibration might be
      associated with a health risk over a long life span.

PMID- 9583317
TI  - Prediction of TTS for hand intermittent vibration.
AB  - Temporary Threshold Shift (TTS) is often used as an indicator of the effect of
      hand-transmitted vibration on the human body. An experiment for the prediction of
      TTS in exposure to intermittent vibration was conducted in the present study to
      examine the exposure equivalent rule, as well as the equations for growth and
      recovery TTS. It was found that the prediction of TTS obtained here was in good
      agreement with measured TTS. This estimation procedure for predicting TTS was
      compared with the notification of the Labor Ministry in Japan, in which control
      of the operation time and the rest time for hand-vibrating tools was described.
      The results suggest that the rest time of five minutes for a continuous exposure
      time of 30 minutes with low-level of vibration tools should be extended to 10
      minutes of rest time.

PMID- 9583318
TI  - Vibration acceleration magnitudes of hand-held tools and workpieces.
AB  - The magnitudes of the hand-transmitted vibration, 297 hand-held tools and
      workpieces were measured at workplaces. The tools were used mainly in
      construction and manufacturing industries. The current standard for the
      measurement of hand-transmitted vibration has been based on the frequency
      weighted acceleration of dominant axis method. According to the proposal of
      ISO/CD5349-1, the results of measurements (462 points) were recalculated by the
      method of the frequency-weighted acceleration sum. There is 32% of difference in
      average value between the acceleration sum and the dominant axis method.

PMID- 9583319
TI  - Arthroplasty for trapeziometacarpal arthrosis.
AB  - We evaluated twenty-eight patients (30 thumbs) after ligament reconstruction
      arthroplasty for trapeziometacarpal arthrosis. The mean age was 60 years, 86%
      were women, and the average follow up was 38 months. Subjective results showed
      excellent (40%) or good (57%) pain relief in 97% of patients. Return to previous
      work or activity level was achieved in 98%. Overall satisfaction was observed in
      86% of patients, mostly because of pain relief. Functional improvement was
      reported for many activities except for jar opening, which continued
      postoperatively to be the most difficult task to perform. Thumb mobility improved
      postoperatively. Key pinch strength showed an overall decrease of 27%. Proximal
      migration of the thumb metacarpal measured 27% and radial subluxation measured
      1%. Thumb metacarpophalangeal joint hyperextension was present in > 50%
      preoperatively and in 7 of 30 thumbs postoperatively. Hyperextension was
      prevalent among women on hormone replacement therapy including three patients who
      had recurrence of these deformities in spite of attempts to stabilize this joint
      during surgery.

PMID- 9583320
TI  - Characteristics and hospital utilization of the Oklahoma Medicare population:
      1994-1996.
AB  - BACKGROUND AND OBJECTIVES: Epidemiologic surveillance reports that focus on
      hospital utilization are limited in number. The objective of this study was to
      provide a current profile of the demographic characteristics of the Oklahoma
      Medicare population and to profile trends in hospital utilization. METHODS: Using
      the Medicare enrollment files and discharge claims data sets for 1994 through
      1996, demographic characteristics and surveillance measures were calculated for
      enrollees based on age, sex, race/ethnicity, principal diagnosis, and primary
      procedure. In addition, average hospital charge and average reimbursement were
      evaluated by diagnosis-related group. RESULTS: The Oklahoma Medicare population
      has grown by 2.5% from 1994 through 1996. The majority (87.5%) of the enrollees
      are aged 65 or greater. Of those less than 65 years of age, most are enrolled in
      the program because of disability. Less than 5% of the Medicare population was
      enrolled in a managed care plan during 1996. The overall length of stay, in
      hospital mortality, and 30-day mortality rates have declined for all age groups
      and principal diagnoses profiled. More than one fifth of all of the Medicare
      discharge claims were related to heart disease. CONCLUSIONS: The Medicare
      discharge claims files represent a useful source of data from which to conduct
      surveillance on this population. The declining rates of mortality and length of
      stay that were demonstrated for all Medicare age groups must be taken into
      account in any evaluation of health care services that seeks to address the
      impact of quality improvement or utilization management strategies over time.

PMID- 9583321
TI  - Nonmarital births in Oklahoma 1975-1995.
AB  - This report uses data from the Oklahoma State Department of Health to describe
      past trends and current patterns of nonmarital births in Oklahoma. Between 1975
      and 1995, the percentage of unmarried women delivering a live birth in Oklahoma
      increased from 12% to 31%. Adult nonmarital births increased faster than teen
      nonmarital births, but teens had a higher percentage of nonmarital births. White
      rates increased faster than African-American and Native American rates, but
      African-Americans had a higher percentage of nonmarital births. Unmarried women
      who give birth were more likely to be poor and lack education; additionally, they
      were less likely to receive early prenatal care, more likely to have had low
      weight births, and more likely to have had an unintended pregnancy. Birth
      outcomes are poorer among unmarried women, but this may be due to poverty and
      education rather than marital status alone.

PMID- 9583322
TI  - Preimplantation Genetic Diagnosis: prevention of serious genetic disorders.

PMID- 9583323
TI  - Proposed new hepatitis A and varicella requirements.

PMID- 9583324
TI  - The stealth acid.

PMID- 9583325
TI  - Social support, conflict, and the development of marital dysfunction.
AB  - How spouses help each other contend with personal difficulties is an unexplored
      but potentially important domain for understanding how marital distress develops.
      Newly married couples participated in 2 interaction tasks: a problem-solving task
      in which spouses discussed a marital conflict and a social support task in which
      spouses discussed personal, nonmarital difficulties. Observational coding of
      these interactions showed that wives' support solicitation and provision
      behaviors predicted marital outcomes 2 years later, independent of negative
      behaviors during marital problem-solving discussions. In addition, couples who
      exhibited relatively poor skills in both behavioral domains were at particular
      risk for later marital dysfunction. These results suggest that social support
      exchanges should be incorporated into social learning analyses of marriage and
      into programs designed to prevent marital distress.

PMID- 9583326
TI  - Transporting an empirically supported treatment for panic disorder to a service
      clinic setting: a benchmarking strategy.
AB  - This work examines the transportability of cognitive-behavioral therapy (CBT) for
      panic disorder to a community mental health center (CMHC) setting by comparing
      CMHC treatment outcome data with the results obtained in two controlled efficacy
      trials. Participants were 110 clients with a primary diagnosis of panic disorder
      with or without agoraphobia; clients were not excluded on the basis of medication
      use or changes, severity or frequency of panic attacks, age, or the presence of
      agoraphobia. Clients completed a 15-session CBT protocol. Despite differences in
      settings, clients, and treatment providers, the treatment outcomes for clients
      completing treatment in the CMHC and the efficacy studies were comparable: Of the
      CMHC clients who completed treatment, 87% were panic-free at the end of
      treatment, and clients showed significant reductions in anticipatory anxiety,
      agoraphobic avoidance, generalized anxiety, and symptoms of depression. The
      present study suggests that panic control treatment can be transported to a CMHC.
      Challenges facing the transportability of research-based treatment to CMHC
      clients, settings, and treatment providers are discussed.

PMID- 9583327
TI  - Comorbid panic disorder and major depression: implications for cognitive
      behavioral therapy.
AB  - Panic disorder and major depression frequently coexist, yet the implications of
      comorbidity for psychological treatments have rarely been studied. The objective
      of this study was to evaluate whether pretreatment comorbidity of major
      depression affects the outcome of cognitive-behavioral treatment (CBT) of panic
      disorder. Thirty-seven clients who met diagnostic criteria for both panic and
      major depression participated in 10 sessions of individual CBT for panic.
      Treatment outcome was contrasted with the outcome of 53 clients having only panic
      disorder who received the same treatment. The co-occurrence of depression did not
      adversely affect CBT for panic. These results have implications for clinical
      practice and theoretical implications for the nature of the relationship between
      panic and depression.

PMID- 9583328
TI  - Peer influences and drug use among urban adolescents: family structure and parent
      adolescent relationship as protective factors.
AB  - The moderating influences of family structure and parent-adolescent distress on
      the relationship between peer variables and drug use were examined in a
      predominantly African American sample of 630 10th graders at 9 urban high
      schools. Both peer pressure and peer drug use were significantly related to the
      reported frequency of drug use. The relationship between peer pressure and drug
      use was stronger among girls than boys, and also among adolescents in families
      without fathers or stepfathers. The association between peer pressure and drug
      use also increased as a function of the level of mother-adolescent distress among
      adolescents who were not living with fathers or stepfathers. Neither gender nor
      family structure moderated the relationship between peer drug models and drug
      use. However, the association between peer drug models and drug use increased as
      a function of the level of mother-adolescent distress.

PMID- 9583329
TI  - Articulated thoughts of maritally violent and nonviolent men during anger
      arousal.
AB  - The cognitive correlates of anger arousal were investigated in community-based
      samples of maritally violent (MV), maritally distressed-nonviolent (DNV), and
      maritally satisfied-nonviolent (SNV) husbands. Participants performed the
      Articulated Thoughts in Simulated Situations (ATSS) paradigm while listening to
      anger-arousing audiotapes. Trained raters coded for irrational beliefs, cognitive
      biases, hostile attributional biases, and anger control statements. Results
      indicated that MV men articulated significantly more irrational thoughts and
      cognitive biases than DNV and SNV men. MV men articulated more hostile
      attributional biases than DNV and SNV men across all ATSS scenarios. SNV men,
      however, articulated more anger control statements during ATSS anger arousal than
      MV or DNV participants. Discriminant function analyses indicated that specific
      thoughts discriminated between the groups and differentiated mildly from severely
      violent participants. ATSS cognitive distortions (a) were not correlated with
      questionnaire measures of cognitive distortion, and (b) were superior to
      questionnaire measures in discriminating between the groups. The findings are
      interpreted in light of recent advances in understanding the relationship between
      information processing, anger, and marital aggression.

PMID- 9583330
TI  - Clinical outcome, consumer satisfaction, and ad hoc ratings of improvement in
      children's mental health.
AB  - Mental health clinics and managed care organizations assess treatment
      effectiveness with consumer satisfaction measures and ad hoc measures of
      improvement obtained from a single informant; some of these measures are as
      simple as asking clients whether they improved during treatment. In the present
      correlational study of 199 treated adolescents, we used a multitrait-multimethod
      analysis to examine psychometrically measured pathology change (pre- and
      postassessment of symptoms and functioning), consumer satisfaction, and perceived
      improvement reported by multiple informants. Confirmatory factor-analytic results
      indicate that (a) outcome variance due to multiple informants cannot be ignored,
      (b) consumer satisfaction is unrelated to pathology change, and (c) parent
      reported perceived improvement ratings are more akin to satisfaction than to
      pathology change.

PMID- 9583331
TI  - Drug abuse day treatment: a randomized clinical trial comparing day and
      residential treatment programs.
AB  - Clients entering a therapeutic community (TC)-oriented drug treatment program
      were randomly assigned to day or residential conditions and interviewed at 2
      weeks and 6 months after admission. Outcomes included Addiction Severity Index
      composite scores and summary scores for the Beck Depression Inventory, Symptom
      Checklist-90-R, and a social support scale. Only clients who remained in
      treatment for at least 2 weeks were included. The mean age of the sample (N =
      261) was 32.9 (SD = 6.7 years) and the mean education level was 12.1 years (SD =
      1.9 years); 30% were women. Comparison of outcome scores at 6 months between
      groups, while controlling for baseline values, indicated greater improvement for
      residential clients on social problems and psychiatric symptoms. The groups were
      similar on the 8 remaining outcomes, including measures of alcohol and drug
      problems. Overall, the level of improvement among day treatment clients was not
      significantly different from that of residential clients.

PMID- 9583332
TI  - Internal validity of Project MATCH treatments: discriminability and integrity.
AB  - Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) is a
      multisite collaborative project designed to evaluate patient-treatment
      interactions in alcoholism treatment. To evaluate whether major threats to the
      internal validity of the independent (treatment) variable in Project MATCH could
      be ruled out, we investigated several aspects of treatment integrity and
      discriminability. In this study, 1,726 alcohol-dependent participants at 10 sites
      were randomized to 3 treatments: cognitive-behavioral treatment (CBT),
      motivational enhancement therapy (MET), and 12-step facilitation (TSF).
      Participants received treatment either as outpatients or as aftercare following a
      more intensive inpatient or day hospital treatment. For both the outpatient and
      aftercare arms of the study, treatments were discriminable in that therapists
      implemented each of the treatments according to manual guidelines and rarely used
      techniques associated with comparison approaches. Participants received a high
      level of exposure to their study treatments, and the intended contrast in
      treatment dose between MET and the 2 more intensive treatments (CBT and TSF) was
      obtained. Alcoholics Anonymous involvement was significantly higher for
      participants assigned to TSF versus MET or CBT, whereas the treatments did not
      differ in utilization of other nonstudy treatments. Nonspecific aspects of
      treatment such as therapist skillfulness and level of the therapeutic alliance
      were comparable across treatment conditions.

PMID- 9583333
TI  - Therapist responsiveness to client interpersonal styles during time-limited
      treatments for depression.
AB  - Effective treatment involves therapists responding appropriately to their
      clients' varying requirements, including clients' predominant interpersonal
      styles. In 2 manualized time-limited treatments for depression, psychodynamic
      interpersonal (PI) and cognitive-behavioral (CB) clients were assigned to 1 of 3
      interpersonal style groups. Therapists, who were not told their clients'
      interpersonal style, nevertheless responded with systematically different
      interventions depending on clients' interpersonal style. Consistent with
      predictions, therapists tended to use more affective and relationship-oriented
      interventions with overinvolved clients, particularly in PI therapy. Therapists
      tended to use more cognitive treatment methods with underinvolved clients,
      particularly in CB therapy. Outcomes of the interpersonal style groups were
      approximately equivalent, consistent with a view that the differences in
      treatment implementation reflected appropriate responsiveness to clients'
      interpersonal styles.

PMID- 9583334
TI  - Treatment decision making and adjustment to breast cancer: a longitudinal study.
AB  - This study monitored women (N = 76) with breast cancer from diagnosis through 1
      year, and tested constructs from subjective expected utility theory with regard
      to their ability to predict patients' choice of surgical treatment as well as
      psychological distress and well-being over time. Women's positive expectancies
      for the consequences of treatment generally were maintained in favorable
      perceptions of outcome in several realms (i.e., physician agreement, likelihood
      of cancer cure or recurrence, self-evaluation, likelihood of additional
      treatment, partner support for option, attractiveness to partner). Assessed
      before the surgical decision-making appointment, women's expectancies for
      consequences of the treatment options, along with age, correctly classified 94%
      of the sample with regard to election of mastectomy versus breast-conserving
      procedures. Calculated from the point of decision making to 3 months later,
      expectancy disconfirmations and value discrepancies concerning particular
      treatment consequences predicted psychological adjustment 3 months and 1 year
      after diagnosis.

PMID- 9583335
TI  - Lower precombat intelligence is a risk factor for posttraumatic stress disorder.
AB  - The authors examined the relation between intelligence and posttraumatic stress
      disorder (PTSD) by studying the association among precombat intelligence, current
      intelligence, and self-reported PTSD symptoms. Military aptitude test results
      were obtained in 59 PTSD and 31 non-PTSD Vietnam combat veterans who had
      undergone a psychodiagnostic interview and current intelligence testing. People
      with lower precombat intelligence were more likely to develop PTSD symptoms as
      assessed by the Clinician-Administered PTSD Scale even after adjustment for
      extent of combat exposure. The association between current intelligence and PTSD
      was no longer significant after adjusting for precombat intelligence. These
      results suggest that lower pretrauma intelligence increases risk for developing
      PTSD symptoms, not that PTSD lowers performance on intelligence tests.

PMID- 9583336
TI  - Parental divorce during early adolescence in Caucasian families: the role of
      family process variables in predicting the long-term consequences for early adult
      psychosocial adjustment.
AB  - The relationship between parental divorce occurring during adolescence and young
      adult psychosocial adjustment was examined, as was the role of family process
      variables in clarifying this relationship. Participants were young Caucasian
      adults from divorced (n = 119) and married (n = 123) families. Assessments were
      conducted during adolescence and 6 years later during early adulthood. Young
      adults from married families reported more secure romantic attachments than those
      from divorced families; however, differences were not evident in other domains of
      psychosocial adjustment after demographic variables were controlled. Three family
      process variables (parent-adolescent relationship, interparental conflict, and
      maternal depressive symptoms) were examined as potential mediators and moderators
      of the association between parental divorce and young adult adjustment. No
      evidence supporting mediation or moderation was found; however, the parent
      adolescent and parent-young adult relationships, particularly when the identified
      parent was the father, emerged as significant predictors of young adult
      psychosocial adjustment.

PMID- 9583337
TI  - Relational and overt forms of peer victimization: a multiinformant approach.
AB  - This research addressed 2 limitations of past research on peer victimization: the
      tendency to study boys only and the tendency to focus on forms of peer
      maltreatment that are common in boys' peer groups (victimization through overt
      aggression) but occur much less frequently in girls' peer groups. Peer- and self
      report instruments were used to assess a relational form of victimization in
      addition to the overt form that has been the focus of past research. Results
      showed that girls were more relationally victimized, whereas boys were more
      overtly victimized. Both forms of victimization were shown to predict concurrent
      sociopsychological adjustment problems significantly (e.g., peer rejection,
      loneliness) beyond aggression. Victims identified through a combination of self-
      and peer-reports were particularly maladjusted.

PMID- 9583338
TI  - Predicting relapse: a meta-analysis of sexual offender recidivism studies.
AB  - Evidence from 61 follow-up studies was examined to identify the factors most
      strongly related to recidivism among sexual offenders. On average, the sexual
      offense recidivism rate was low (13.4%; n = 23,393). There were, however,
      subgroups of offenders who recidivated at high rates. Sexual offense recidivism
      was best predicted by measures of sexual deviancy (e.g., deviant sexual
      preferences, prior sexual offenses) and, to a lesser extent, by general
      criminological factors (e.g., age, total prior offenses). Those offenders who
      failed to complete treatment were at higher risk for reoffending than those who
      completed treatment. The predictors of nonsexual violent recidivism and general
      (any) recidivism were similar to those predictors found among nonsexual criminals
      (e.g., prior violent offenses, age, juvenile deliquency). Our results suggest
      that applied risk assessments of sexual offenders should consider separately the
      offender's risk for sexual and nonsexual recidivism.

PMID- 9583339
TI  - Nondieting versus dieting treatment for overweight binge-eating women.
AB  - This study evaluated the effectiveness of nondieting versus dieting treatments
      for overweight, binge-eating women. Participants (N = 219) were randomly assigned
      to 1 of 3 groups: diet treatment (DT), nondiet treatment (NDT), or wait-list
      control (WLC). DT received a balanced-deficit diet reinforced with behavioral
      strategies. NDT received therapy designed to help participants break out of their
      dieting cycles. Treatment in both conditions was administered in weekly groups
      for 6 months, followed by 26 biweekly maintenance meetings, for a total of 18
      months of contact. At 6 months posttreatment, DT lost 0.6 kg while NDT gained 1.3
      kg. Both treatment groups reduced their Binge Eating Scale scores significantly
      more than WLC. At 18-month follow-up, both treatment groups experienced weight
      gain but maintained similar reductions in binge eating. Results indicate that
      neither intervention was successful in producing short- or long-term weight loss.
      Therapist biases, which may have affected treatment integrity, and other
      methodological issues are discussed in relation to the small weight losses
      achieved.

PMID- 9583340
TI  - Attributions for positive life events predict recovery from depression among
      psychiatric inpatients: an investigation of the Needles and Abramson model of
      recovery from depression.
AB  - The authors investigated whether attributions for positive life events predict
      decreases in hopelessness and depressive symptoms among clinically depressed
      adults. Measures of attributional style, attributions for recent events,
      depressive symptoms, dysfunctional attitudes, hopelessness, and life events were
      administered to 52 depressed psychiatric inpatients treated with antidepressant
      medication; the measures were readministered 12 and 24 days later. Results
      indicated that (a) internal, stable, global attributions for recent positive
      events mediated a significant association between attributional style for
      positive life events and decreased hopelessness; (b) decreases in hopelessness
      mediated a significant association between internal, stable, global attributions
      for recent positive events and decreases in depressive symptom levels; and (c)
      depressotypic cognitions were not associated with decreases in either
      hopelessness or depressive symptom levels.

PMID- 9583341
TI  - Cognitive-behavioral treatment for depression: relapse prevention.
AB  - This study presents 2-year follow-up data of a comparison between complete
      cognitive-behavioral therapy for depression (CT) and its 2 major components:
      behavioral activation and behavioral activation with automatic thought
      modification. Data are reported on 137 participants who were randomly assigned to
      1 of these 3 treatments for up to 20 sessions with experienced cognitive
      behavioral therapists. Long-term effects of the therapy were evaluated through
      relapse rates, number of asymptomatic or minimally symptomatic weeks, and
      survival times at 6-, 12-, 18-, and 24-month follow-ups. CT was no more effective
      than its components in preventing relapse. Both clinical and theoretical
      implications of these findings are discussed.

PMID- 9583342
TI  - Direct and indirect latent-variable parenting outcomes of two universal family
      focused preventive interventions: extending a public health-oriented research
      base.
AB  - Recent literature underscores the need for studies of family-based preventive
      interventions oriented toward public health objectives. This article illustrates
      a program evaluation approach for the study of family intervention outcomes in
      general populations. Thirty-three rural schools were randomly assigned to 1 of 3
      conditions: the Preparing for the Drug-Free Years Program (PDFY), the Iowa
      Strengthening Families Program (ISFP), and a minimal-contact control group. Self
      report and observational data collected from 523 families were used to develop
      measurement models of 3 latent parenting constructs that included measurement
      method effects. Analyses were conducted to ensure initial and attrition-related
      group equivalencies and to assess school effects. Structural equation models of
      the hypothesized sequence of direct and indirect effects for both PDFY and ISFP
      were then fit to the data. All hypothesized effects were significant for both
      interventions. The discussion addresses the potential public health benefits of
      evaluation research on universal preventive interventions.

PMID- 9583343
TI  - A multiperspective, multivariable evaluation of reliable change.
AB  - N. S. Jacobson and P. Truax's (1991) method for evaluating the clinical
      significance of client change has gained some prominence in psychotherapy outcome
      research. However, little has been done to investigate the validity of this
      methodology. This study addresses this limitation by comparing (a) the perceived
      level of change (as subjectively reported from 3 distinct perspectives) across
      outcome groupings based on Jacobson and Truax's reliable change index (RCI) and
      (b) subjective reports of therapeutic alliance and satisfaction across outcome
      groupings. The results of these comparisons indicate that the RCI is effective in
      identifying those who make reliable improvement in therapy but is less effective
      in differentiating between no-changers and deteriorators. In addition, the
      relationship between treatment outcome and satisfaction with service is
      questioned.

PMID- 9583344
TI  - The use of religious coping during stressful life events: main effects,
      moderation, and mediation.
AB  - The effects of religious coping, the potential moderation of such effects by
      religious affiliation (i.e., Catholic, Protestant), and the potential mediation
      of such effects by various factors (i.e., cognitive restructuring, social
      support, perceived control) were investigated in patients and significant others
      coping with the stress of kidney transplant surgery. At 3 and 12 months after
      transplantation, results showed that the use of religious coping was generally
      associated with better adjustment both concurrently and over time in both
      patients and significant others. These effects were moderated by religious
      affiliation, such that religious coping was more effective in promoting
      adjustment for Protestants than for Catholics. Religious coping was related to
      adjustment beyond the effects of the proposed mediators. Implications of these
      results for future research and practice are discussed.

PMID- 9583345
TI  - When and how perfectionism impedes the brief treatment of depression: further
      analyses of the National Institute of Mental Health Treatment of Depression
      Collaborative Research Program.
AB  - Perfectionism has previously been identified as having a significant negative
      impact on therapeutic outcome at termination in the brief (16-week) treatment of
      depression (S. J. Blatt, D. M. Quinlan, P. A. Pilkonis, & T. Shea, 1995) as
      measured by the 5 primary outcome measures used in the National Institute of
      Mental Health Treatment of Depression Collaborative Research Program (TDCRP). The
      present analyses of other data from the TDCRP indicated that this impact of
      perfectionism on therapeutic outcome was also found in ratings by therapists,
      independent clinical evaluators, and the patients and that this effect persisted
      18 months after termination. In addition, analyses of comprehensive, independent
      assessments made during the treatment process indicated that perfectionism began
      to impede therapeutic gain in approximately 2/3 of the sample, in the latter half
      of treatment, between the 9th and 12th sessions. Implications of these findings
      are discussed, including the possibility that more perfectionistic patients may
      be negatively impacted by anticipation of an arbitrary, externally imposed
      termination date.

PMID- 9583346
TI  - Exercise and the maintenance of weight loss: 1-year follow-up of a controlled
      clinical trial.
AB  - This study reports results 1 year after treatment for 77 obese women who had been
      treated for 48 weeks by diet combined with supervised (a) aerobic exercise, (b)
      strength training, (c) aerobic plus strength training combined, or (d) no
      exercise. Mean (+/- SD) end-of-treatment weight losses for the 4 conditions
      ranged from 13.5 +/- 9.1 kg to 17.3 +/- 10.3 kg, but there were no statistically
      significant differences among groups. Participants in all 4 conditions regained
      approximately 35% to 55% of their weight loss in the year after treatment; again,
      there were no significant differences among groups. Participants, however, who
      reported exercising regularly in the 4 months preceding the follow-up assessment
      regained significantly less weight than did nonexercisers.

PMID- 9583347
TI  - Cognitive and physical capacity process variables predict long-term outcome after
      treatment of chronic pain.
AB  - Cognitive-behavioral and physical therapies are incorporated into
      multidisciplinary chronic pain programs because changes in pain cognitions and
      physical capacity may represent therapeutic processes that facilitate favorable
      outcome. Decreases in depression, however, may explain treatment responses more
      parsimoniously. Measures of pain helplessness, lifting capacity, walking
      endurance, depression, pain severity, and activity level were collected from 94
      chronic pain patients at pre- and posttreatment and at 3- to 6-month follow-up
      evaluations. Decreases in pain helplessness were linked to pain severity
      reduction, whereas walking endurance increases were related to improvements in
      activity levels and downtime even after controlling for effects of depression
      decreases. Thus, cognitive and physical capacity changes that occur through pain
      treatment may make unique contributions to long-term outcome.

PMID- 9583348
TI  - The multiple roles of macrophage scavenger receptors (MSR) in vivo: resistance to
      atherosclerosis and susceptibility to infection in MSR knockout mice.
AB  - Both type I and type II MSRs are integral membrane proteins containing a
      collagenous domain and elicit an extraordinarily wide range of ligand binding
      capability. They were found during the search for the molecule(s) responsible for
      the accumulation of modified LDL during atherogenesis. However, all prior the
      evidence relating to their physiological and pathophysiological roles in vivo had
      been indirect. Targeted disruption of the MSR gene results in a reduction in the
      size of atherosclerotic lesions in an apo E deficient animal. Macrophages from
      MSR deficient mice exhibit a marked decrease in modified LDL uptake in vitro,
      whereas modified LDL clearance from plasma remains normal, suggesting that there
      are alternative mechanisms for the uptake of modified LDL from the circulation.
      In addition, MSR knockout mice are more susceptible to L. monocytogenes and HSV-1
      infection, indicating a role for MSR in host defense against various pathogens.

PMID- 9583350
TI  - A novel member of the LDL receptor gene family with eleven binding repeats is
      structurally related to neural adhesion molecules and a yeast vacuolar protein
      sorting receptor.
AB  - We now have discovered and characterized a novel multi-domain protein and
      classified it as a member of the LDL receptor gene family. The approximately 250
      kDa membrane protein, termed LR11, highly conserved in man, rabbit and chicken,
      contains a cluster of 11 LDL receptor ligand binding repeats, a group of 5 LDL
      receptor "YWTD" repeats, a large hexarepeat domain of structural elements found
      in neural cell adhesion molecules, and a domain with similarity to a yeast
      receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits
      features typical of endocytosis-competent coated pit receptors. The mosaic, and
      presumably multifunctional, receptor is expressed abundantly in brain, liver and
      adrenal glands. Ligand blotting of LR11-transfected cells demonstrated that LR11
      binds apolipoproteinE-containing lipoproteins, as well as other members of LDL
      receptor gene family. In contrast to the LDL receptor, the mRNA levels in rabbit
      liver is unaffected by hyperlipidemia. The features of this highly conserved and
      complex mosaic protein suggest the importance of the ever expanding LDL receptor
      gene family in the evolution and proposed multifunctionality.

PMID- 9583349
TI  - Potential role of a novel vascular modulator, hepatocyte growth factor (HGF), in
      cardiovascular disease: characterization and regulation of local HGF system.
AB  - Since endothelial cells (EC) are known to secrete various anti-proliferative and
      vasodilating factors, an agent that promotes seeding or regeneration of EC may
      have potential therapeutic value against vascular smooth muscle cell (VSMC)
      proliferation. To seek an endothelium specific growth factor, we have focused on
      hepatocyte growth factor (HGF). HGF is belonged to a member of endothelium
      specific growth factors, whose mitogenic action on EC was most potent among
      growth factors. Moreover, the presence of local HGF system (HGF and its specific
      receptor, c-met) was observed in EC and VSMC of rat and human in vitro as well as
      in vivo. Production of local HGF production in vascular cells was regulated by
      various cytokines including transforming growth factor (TGF)-beta and angiotensin
      II (Ang II). Furthermore, HGF may be a therapeutic growth factor for the
      treatment of restenosis after angioplasty and arteriosclerosis obliterance, etc.,
      as gene therapy. From these characteristics of HGF, we hypothesized that HGF
      might contribute to the protection or repair of vascular endothelial cells.
      Indeed, serum HGF concentration was significantly correlated with blood pressure,
      suggesting that HGF secretion might be elevated in response to high blood
      pressure as a counter-system against endothelial dysfunction. In this review, we
      discussed that HGF is a member of the endothelium specific growth factors whose
      serum concentration is significantly associated with blood pressure.

PMID- 9583351
TI  - Blood coagulability and fibrinolysis in streptozotocin-induced diabetic rats.
AB  - Changes in coagulation and fibrinolysis in the plasma (in vivo) and hepatocytes
      (ex vivo) were studied using hyperglycemic rats. Hyperglycemia was induced by
      intravenous injection of 50 mg/kg streptozotocin (STZ). Eight weeks after the
      injection, we observed increases in thrombin-antithrombin III complex and tissue
      type plasminogen activator activity, decreases in plasma levels of antithrombin
      III, plasminogen and alpha2-plasmin inhibitor, and significant shortening of
      activated partial thromboplastin time. In freshly isolated or cultured
      hepatocytes from STZ-induced hyperglycemic rats, concentrations of proteins
      related to coagulation were increased. An increase in alanine-aminotransferase
      leakage and decreases in the levels of amylase, triglycerides and phospholipids
      were observed in the culture medium of hepatocytes from STZ treated rats. In vivo
      study revealed that STZ-induced subchronic diabetes induced imbalance between
      coagulation and fibrinolysis, and ex vivo study in hepatocytes from STZ-treated
      rats showed membrane degeneration and reduction in amylase synthesis, while
      protein synthesis related to coagulation was not inhibited. These results suggest
      that, despite vulnerability of liver cells from STZ treated rats, coagulation
      activity in the liver is retained and rather enhanced in STZ-induced
      hyperglycemic rats, which may contribute to the promotion of atherosclerosis.

PMID- 9583352
TI  - Relation of abdominal and thigh adipose tissue distribution to serum lipids and
      glucose metabolism in obese males.
AB  - Spin-echo magnetic resonance imaging (MRI) and postprocessing for fat
      quantification were used to examine the relationship of abdominal and thigh
      adipose-tissue distribution to serum lipids and glucose metabolism in obesity.
      Thirteen simple obese male patients and 12 non-obese male volunteers were
      examined by MRI, blood pressure, and fasting blood sample levels of serum lipids,
      glucose, immunoreactive insulin, c-peptide, HbA1C and hematocrit. Correlations of
      thigh visceral and subcutaneous fat areas to serum lipid levels were generally
      similar, but marked differences were found between relationships of thigh versus
      abdominal fat areas to serum lipid levels. In addition, diastolic blood pressure
      was significantly correlated with the fat area, especially with the abdominal
      visceral fat area (r=0.51, p<0.01), but not with abdominal subcutaneous fat area.
      The thigh muscle area was highly and inversely correlated with c-peptide (r=
      0.72, p<0.01) and systolic blood pressure (r=-0.65). Differences in correlations
      between visceral and subcutaneous fat areas in the abdomen to metabolic
      parameters were found between abdominal visceral fat areas and HbA1C and between
      the abdominal subcutaneous fat areas and HbA1C. These findings suggest that the
      character of regional fat could be heterogeneous with respect to lipid and
      glucose metabolism and blood pressure levels in obese males.

PMID- 9583353
TI  - Influence of apolipoprotein E polymorphism on bezafibrate treatment response in
      dyslipidemic patients.
AB  - To examine the significance of apolipoprotein E (apo E) polymorphism in the
      hypolipidemic effect of bezafibrate, we evaluated the influence of different apo
      E phenotypes on serum lipid response to bezafibrate treatment in 58 dyslipidemic
      patients with WHO phenotypes of IIb, IV, or isolated hypo HDL cholesterolemia.
      Patients were categorized into one of three groups according to apo E phenotypes
      of E2 (E2/3, n=5), E3 (E3/3, n=35), and E4 (E3/4 and E4/4, n=18). After 3 months
      daily administration of 400 mg bezafibrate, serum total cholesterol (TC) and low
      density lipoprotein cholesterol (LDLC) levels changed on average in the E3 group
      [-8.0%; p<0.05 and +1.1%; not significant (ns), respectively], the E2 group (
      18.3%; p<0.005 and -26.9%; p<0.05, respectively) and the E4 group (+3.8%; ns and
      +10.1%; ns, respectively). The changes in TC and LDLC levels in the E4 group was
      significantly less effective compared with those in the E3 (p<0.05) and E2 groups
      (p<0.01). Bezafibrate induced a reduction in serum triglyceride (TG) levels in
      the E3 group (-50.1%; p<0.0001), the E2 group (-46.9%; p<0.05) and the E4 group (
      44.8%; p<0.005). An increase in high-density lipoprotein cholesterol (HDLC)
      levels was also observed in the E3 group (+27.5%; p<0.0001), the E2 group
      (+35.0%; ns) and the E4 group (+38.8%; p<0.005). However, there was no
      significant difference in the changes of TG and HDLC levels between the groups.
      These results suggest an important role of apo E polymorphism in modulating serum
      lipid response to bezafibrate, and phenotyping of apo E helps predict the
      therapeutic effect of bezafibrate treatment.

PMID- 9583354
TI  - A monoclonal antibody-based enzyme immunoassay for the measurement of native and
      glycated apolipoprotein B-containing particles.
AB  - We describe the development of sandwich enzyme-linked immunosorbent assays
      designed to measure native and glycated apolipoprotein B containing particles in
      plasma. The assays utilize monoclonal antibodies anti native or glycated apo B
      LDL for coating and a polyclonal anti apoB-LDL-peroxidase conjugate as the
      detecting antibody. The method is specific, sensitive and precise. The intra
      assay coefficient of variation for the plasma native and glycated apolipoprotein
      B-containing particles was determine to be 7.8% and 7.5%, respectively. The
      method described can provide specific and reproducible determinations of apoB and
      glycated-apoB containing particles in plasma; it will be of great interest in the
      evaluation of atherosclerotic risk in dyslipoproteinemic states in diabetic and
      non-diabetic subjects.

PMID- 9583355
TI  - Significance of antisperm antibodies in female serum in a gamete intrafallopian
      transfer program.
AB  - The influence of antisperm antibodies in the female serum on fertilization and
      pregnancy rate in patients undergoing GIFT was assessed. A study group of 52
      couples (69 cycles) with significant levels of antisperm antibodies in the female
      serum were compared to a control group of 749 couples (1185 cycles). Maternal
      serum or donor serum was used as growth medium supplement. The TAT test was
      performed for the detection of antisperm antibodies in the serum. Antisperm
      antibody presence in female serum was associated with similar fertilization and
      pregnancy rates in a GIFT program compared to the control group. The type of
      serum used as growth medium supplement did not affect statistically the
      fertilization or pregnancy rate.

PMID- 9583356
TI  - Effect of a combined GnRH/hCG therapy in boys with undescended testicles:
      evaluated in relation to testicular localization within the first week after
      birth.
AB  - Among 509 boys referred with undescended testicles, 112 had true undescended
      testicles unilaterally and 62 bilaterally. Patients with true undescended
      testicles were offered hormonal treatment unless the condition was associated
      with hernia or previous operations. Boys less than 5 years old were primarily
      treated with gonadotrophin releasing hormone (GnRH), while boys more than 5 years
      old were primarily treated with human chorionic gonadotrophin (hCG). If the
      effect of the primary treatment was insufficient the other hormone was given.
      Testicular descent was obtained for 64% (23/36) of the intraabdominally located
      testicles in boys with bilaterally undescended testicles versus only 14% (3/21)
      in boys with unilaterally undescended testicles (p < .001). Treating 1 to 4 years
      old boys with GnRH resulted in descent in 16 of 95 testicles and secondary
      treatment with hCG yielded an additional 34, whereas secondary treatment of 5 to
      13 years old boys with GnRH added only 10 descended testicles to 51 of 101
      testicles. Reading the maternity records of 272 of the boys support other studies
      showing that testicles may reascend. Boys with endocrinological or "surgical"
      causes of incomplete testicular descent were relatively more likely to have had
      one or two undescended testicles during the first postnatal week compared with
      boys found to have only retractile testicles (p < .001). Treatment with hormones
      resulted in descent in 56% of boys whose testicles were both descended within one
      week after birth. Conversely, only 1 of 20 boys with unilateral testicular
      undescent postnatally was sufficiently treated with hormones (p < .001). The
      hormonal effect in boys with bilaterally undescended testicles at delivery did
      not differ significantly from boys with either one or none undescended testicle
      postnatally. In 35 of 51 boys (69%) in whom the hormonal effect was insufficient,
      operation revealed a "surgical cause" of the incomplete testicular descent.

PMID- 9583357
TI  - Recent advances in clinical/molecular andrology.
AB  - During the last decade there were extensive investigations in clinical and
      molecular andrology with emphasis on assisted reproduction, micromanipulation
      techniques of gametes, sperm/egg interaction, male contraception, diabetes
      mellitus, varicocele, andropause versus menopause, sexual dysfunction, associated
      hypertension/stress, prostatic carcinoma and molecular parameters of male
      reproduction. Sperm hyperactivation is a required step in capacitation sequence.
      Sperm motility is measured by videotape to evaluate the Straight Line Velocity
      (microm/s) (VSLI). Fertilization/embryonic development results from single sperm
      transfer (S-MIST) and multiple sperm transfer. Fertilization/embryo development
      is achieved by injection of immotile sperm into the perivitelline space. To
      assess sperm viability, a supravital stain suitable for use in combination with
      immunofluorescent assay, Hoeschst 33258, is used. The dye fluoresces with an
      intense blue when bound to DNA. To assess sperm plasma membrane integrity, a hypo
      osmotic swelling test (HOST) is performed, using fluoresceinated D-mannose
      enriched albumin (FITC-DMA). The ability of sperm to swell under hypo-osmotic
      conditions indicates an intact membrane. A human protein, C-peptide, thought to
      be a useless byproduct of insulin may protect against devastating heart and nerve
      damage that diabetes causes. Human diabetics may benefit from the substance. Over
      15 million Americans have diabetes, in which blood sugar levels rise out of
      control. There are two types of diabetics: Type I diabetics produce no insulin,
      the hormone that regulates blood sugar. Type II diabetics are unable to use their
      insulin properly. Diabetics are at great risk of heart disease and nerve damage,
      as arteries throughout the body leak and nerve-cell impulses fail. C-peptide is a
      byproduct of insulin production; it can be produced by the body or synthetically.
      Production of this protein is not induced by insulin, so diabetics who take
      insulin do not get C-peptide with it. Varicocele occurs unilaterally on the left
      side in 78% to 93% of men. Typically the presence of a varicocele is associated
      with an abnormal semen analysis (sperm density and morphology) and a decreased
      testicular volume on the affected side. Impaired sperm motility occurs in 89.5%
      of all varicocele patients. Varicocele ligation improves semen parameters in two
      thirds of patients. A few studies on andropause included sexual dysfunction,
      hormonal changes, medical/psychological correlates of impotence,
      ostenopenia/osteoporosis and bone loss; indices of bone remodeling, testosterone
      supplementation, androgen, negative feedback and hypothalamo-pituitary-testicular
      axis. Prostatic cancer is the second leading cause of cancer death for men
      between the ages of 60 and 80. Early detection involves a simple blood test for
      prostate specific antigen (PSA). Regular screening and early detection are
      essential. This is an important test because a high antigen count can be the only
      symptom. Since no screening is 100% accurate, physicians recommend both a PSA
      blood test and a physical examination. Although heredity plays a major role in
      whether a man will develop prostate cancer, men who lead healthy lives can
      dramatically reduce their chances of cancer: low-fat diet, eating plenty of
      fruits and vegetables and not smoking. Recent advances in molecular andrology
      include peptide hormone binding proteins; gonadotropin-releasing hormone (GnRH)
      agonists/antagonists analog; gonadotropins/their receptors; growth
      factors/reproduction; peptides as intratesticular regulators; molecular cloning
      of reproductive proteins/peptides. Gene cloning is applied for
      characterization/expression of genes coding. The interaction of gp120 with CD4
      receptor plays a role in syncytium formation, apoptosis and CD4 cell deletion in
      human immunodeficiency virus (HIV) infection. The recombinant V3 peptide of
      fragment 307-330 of HIV-1 can induce sperm head agglutination. The generation
      process of react

PMID- 9583358
TI  - Levels of interferon alpha and gamma in seminal plasma of normozoospermic,
      oligozoospermic,and azoospermic men.
AB  - The functions of the interferons in the testis are unclear. We investigated the
      role of interferon alpha and gamma in the seminal plasma on spermatogenesis. The
      levels of interferon alpha and gamma were determined in the seminal plasma of 101
      males including normozoospermic (n = 31), oligozoospermic (n = 57) and
      azoospermic men (n = 13). The correlation between such levels and clinical
      parameter (seminogram and serum hormone levels) was evaluated. The seminal plasma
      level of interferon alpha (92.0 + 110.3 ng/mL) in the normozoospermic men was
      significantly lower than that of oligozoospermic men (162.4 +/- 130.3 ng/mL) (p <
      .05). The three groups (normozoospermic, oligozoospermic, and azoospermic group)
      did not differ as to the level of interferon gamma. No significant correlations
      were observed between the levels of interferon alpha or gamma in seminal plasma
      and the serum levels of follicle stimulating hormone (FSH), luteinizing hormone
      (LH), testosterone, prolactin, or estradiol. Theses results suggest that the
      level of interferon alpha in the seminal plasma may be related to sperm
      production.

PMID- 9583359
TI  - Quantitative assessment of human sperm acrosome reaction by using fluorescein
      isothiocyanate conjugated concanavalin A--comparison between highly purified
      acrosome reacted with non-acrosome reacted sperm.
AB  - In the present study, to achieve quantitative assessment of human sperm acrosome
      reaction by using fluorescein isothiocyanate conjugated Concanavalin A (FITC-Con
      A), the optimum conditions for microscopic observation were established by
      comparing the fluorescent images between the purified human sperm with the intact
      acrosome (non-acrosome reacted sperm; non-AR sperm) and those with exposed inner
      acrosomal membrane (acrosome reacted sperm; AR sperm). FITC-Con A stained not
      only the inner acrosomal membrane but also the other portions. These non-specific
      bindings were excluded by the competitive dissociation with alpha-D-mannose (Man)
      solution, the specific labeling of the inner acrosomal membrane with FITC-Con A
      was accomplished in the presence of 0.5 mg/mL Man. The influence of methanol
      fixation on the acrosome status were examined. The assessment of the acrosome
      reaction should evaluate whether the inner acrosomal membrane is exposed or
      masked by the plasma membrane, and methanol fixation is often employed in the
      histochemical stain. By methanol fixation, the fluorescent profiles of AR sperm
      were not altered before and after the treatment, bright fluorescence were found
      in the acrosomal regions. On the other hand, non-AR sperm gave weak fluorescence
      on the sperm heads before the treatment, the acrosomal regions fluoresced
      brightly after the treatment similar to those of AR sperm. Methanol fixation
      caused false positive results, it might denaturate the plasma membranes and
      facilitate permeability of FITC-Con A. FITC-Con A fluorescent stain and the
      modified triple stain (rose bengal stain) gave good positive correlation to
      evaluate AR sperm. This result concluded that the optimum conditions with FITC
      Con A stain in the present procedure might be an useful tool for observation of
      human sperm acrosome reaction.

PMID- 9583360
TI  - Ventral prostate structure and serum testosterone levels after chronic treatment
      with isoproterenol in adult rats with different androgen status.
AB  - The effects of chronic administration of the beta-adrenergic agonist
      isoproterenol (ISO) (120 microg/kg per day; subcutaneously) on the ventral
      prostate structure and serum testosterone concentrations were examined in adult
      rats with different androgen status: intact, intact testosterone-injected (1
      mg/rat), surgically and chemically castrated rats. Chemical castration was evoked
      by an intraperitoneal injection of ethane dimethanesulfonate (EDS) (75 mg/kg). A
      ventral prostate response was only observed in intact and chemically castrated
      animals. Stereological analysis revealed atrophic changes in the glandular
      compartment of the prostate of ISO-treated intact rats, but they were probably
      the consequence of significantly decreased serum testosterone levels. In
      addition, in these animals alterations were found in the morphometrical
      parameters of the ventral prostate blood vessels, their relative and total
      volumes being increased. In chemically castrated rats, administration of ISO from
      the day of EDS application partially prevented the postcastrational regression of
      the ventral prostate without affecting blood testosterone level. However, it
      seems that the discharge of glandular secretion was attenuated at the same time.
      These results show that chronic treatment with ISO may have both stimulatory and
      inhibitory effects on the rat ventral prostate depending on the androgen status
      of the animals and, accordingly, on the site of ISO-action.

PMID- 9583361
TI  - Spermatozoa recovered by IxaPrep gradient have improved longevity and better
      motion characteristics than those by Percoll gradient.
AB  - To compare the effectiveness of various sperm preparation methods, we examined
      sperm concentration, percentage of progressive motility, recovery rate, and
      various motion characteristics in 32 semen samples after Percoll and IxaPrep
      preparations. Except for sperm concentration, which was much higher after IxaPrep
      preparation, no statistical differences existed between these two methods in
      terms of motile sperm concentration (MSC), recovery rate, mean curvilinear
      velocity (VCL), mean straight-line velocity (VSL) and mean amplitude of lateral
      head displacement (ALH). Among 22 samples that were allocated in a 37 degrees C,
      5% CO2 incubator, the mean MSC after 3 hours was significantly higher following
      IxaPrep preparation than following Percoll preparation (63.2 x 10(6)/mL vs. 42.8
      x 10(6)/mL, p < .03). VCL and VSL were much higher after IxaPrep preparation than
      after Percoll preparation, both at 3 hours (p < .01) and at 24 hours (p < .03).
      ALH was also higher after IxaPrep preparation than after Percoll preparation, and
      it was statistically significant after 3 hours of incubation (p < .03). We
      conclude that the IxaPrep gradient may be adopted as the preferred method to the
      Percoll gradient in preparing spermatozoa for assisted reproduction because of
      the spermatozoa's persistent and better motion activities after incubation.

PMID- 9583362
TI  - Dissociation of force production from MHC and actin contents in muscles injured
      by eccentric contractions.
AB  - The primary purpose of this study was to determine the relationship between
      myosin heavy chain (MHC) and actin contents and maximum isometric tetanic force
      (Po) in mouse extensor digitorum longus (EDL) muscles following eccentric
      contraction-induced injury. Po and protein contents were measured in injured (n =
      80) and contralateral control (n = 80) EDL muscles at the following time points
      after in vivo injury: sham, 0, 0.25, 1, 3, 5, 14, and 28 days. Po was reduced by
      37 +/- 2.3% to 49 +/- 3.8% (p < or = 0.05), while MHC and actin contents were
      unaltered from 0 to 3 days after injury. Whereas Po partially recovered between 3
      and 5 days (from -49 +/- 3.8% to -35 +/- 3.6%), MHC and actin contents in the
      injured muscles declined by 19 +/- 4.9% and 20 +/- 5.3%, respectively, by 5 days
      compared with control muscles. Decrements in Po were similar to the reductions in
      MHC and actin contents at 14 (approximately 24%) and 28 (approximately 11%) days.
      Evaluation of myofibrillar and soluble protein fractions indicated significant
      reductions in the content of major proteins at 5 and 14 days. Immunoblots of heat
      shock protein 72 revealed elevations starting at 0.25 days, peaking during 1-3
      days, and declining after 5 days. These findings indicate that decreased
      contractile protein content is not related to the initial decrease in Po.
      However, decreased MHC and actin contents could account for 58% of the Po
      reduction at 5 days, and for nearly all the decrements in Po from 14 to 28 days.

PMID- 9583363
TI  - A six-module human nebulin fragment bundles actin filaments and induces actin
      polymerization.
AB  - We have investigated the interaction of a 6-repeat recombinant human nebulin
      fragment (S6R2R7) with F-actin, with Mg2+-induced actin paracrystals, and G
      actin, respectively. This fragment corresponds to super-repeat 6, repeat 2 to 7
      of human nebulin, and is located in the N-terminal part of the super-repeat
      region of the nebulin molecule. The S6R2R7 fragment included an immuno-tag of
      three amino-acid residues (EEF) at one end which was detectable by a monoclonal
      anti-tubulin YL1/2. By a cosedimentation assay, interaction between F-actin and
      S6R2R7 was observed. Electron microscopy revealed the formation of large bundle
      like aggregates containing highly parallelized actin filaments, apparently caused
      by actin bundling of the nebulin fragment. Compared with Mg2+-induced actin
      paracrystals where the helices of the actin filaments are arranged in register,
      the filaments in the actin-nebulin bundles seem to be packed in a different way
      and show no obvious periodicity. The bundles were also visible in the light
      microscope, and immunofluorescence microscopy revealed binding of the nebulin
      fragment S6R2R7 to both preformed Mg2+ paracrystals and to F-actin. We also
      analyzed the effect of S6R2R7 on actin under non-polymerizing conditions by
      cosedimentation assays and pyrene actin fluorimetry, as well as fluorescence
      microscopy and electron microscopy. Nebulin-induced actin polymerization was
      observed with an enhancement of the nucleation step indicating a stabilization of
      actin nuclei by S6R2R7. Light and electron microscopy revealed bundle-like actin
      nebulin aggregates similar to those formed by pre-assembled F-actin and S6R2R7.
      Thus, even in the absence of salt, S6R2R7 promotes actin polymerization and
      induces formation of tightly packed actin filament bundles. We assume that the
      actin filaments are crosslinked by the nebulin fragments, indicating a rather low
      cooperativity of binding to a single filament.

PMID- 9583364
TI  - The effects of stretch parameters on eccentric exercise-induced damage to toad
      skeletal muscle.
AB  - Repeated contractions during which a muscle is stretched, known as eccentric
      contractions, have previously been shown to produce damage. This can be
      quantified by changes in various mechanical properties, of which reduction in
      tension and a shift in the optimum length for tension generation to longer
      lengths are examined here. The magnitude of these changes has been reported to
      depend strongly on the number of stretches, the amplitude of each stretch and the
      maximum tension reached. One proposed explanation of the changes predicts that
      muscle length should have a strong influence, but past reports have been
      contradictory on this point. Experiments were performed to test this hypothesis
      using whole toad sartorius muscles, which have the advantage of a relatively
      small passive tension, allowing a large range of lengths to be used. Initial
      length, amplitude of stretch and number of eccentric contractions were found by
      multiple linear regression to be the strong determinants of changes due to
      eccentric exercise. Velocity had a weak effect, and tension, varied only by
      varying the length of maximally activated muscles, was poorly correlated.

PMID- 9583365
TI  - Temperature sensitivity of force and shortening velocity in maximally activated
      skinned smooth muscle.
AB  - We have studied the temperature dependence of isometric force, rate of force
      development and maximal shortening velocity (Vmax) in skinned guinea-pig taenia
      coli smooth muscle. To eliminate the influence of temperature on activation
      mechanisms, maximally thiophosphorylated preparations were used. Isometric force
      in the range 2-35 degrees C was maximal at 22 degrees C with a decrease of 25% at
      2 degrees C and 10% at 35 degrees C. Rate of tension development from rigor after
      photolytic release of ATP increased four-fold between 5 degrees C and 30 degrees
      C. Vmax increased with a Q10 of about 2 (1.6, range 5-15 degrees C, and 2.2,
      range 22-30 degrees C). The temperature dependence of the rate of tension
      development indicates rate-limitation by transitions into force-generating states
      or by the hydrolysis reaction. The temperature dependence of Vmax reflects
      effects of temperature on reactions (e.g. the ADP-release) associated with cross
      bridge detachment. The small temperature dependence of steady-state force in
      smooth compared with skeletal muscle suggests differences in the cross-bridge
      reactions controlling the number of attached force-generating states in the two
      muscle types.

PMID- 9583367
TI  - Highlights of the Molecular Interactions of Actin meeting, Hawaii, 1-5 April
      1997.

PMID- 9583366
TI  - Comparative analysis of satellite cell properties in heavy- and lightweight
      strains of turkey.
AB  - The growth of muscle during postnatal development results partly from the
      proliferation of satellite cells and their fusion with muscle fibres. We analysed
      the properties of satellite cells in a heavyweight (HW) turkey strain
      characterized by high body weight and a fast growth rate, and in a lightweight
      farm strain (LW) characterized by low body weight and a slow growth rate.
      Satellite cell activation was then examined in stretched-overloaded anterior
      latissimus dorsi (ALD) muscle by weighting one wing in young turkeys from both
      strains. As early as day 1 of stretching for HW and day 2 for LW, small embryonic
      like fibres expressing ventricular cardiac myosin heavy chain (MHC) isoform were
      observed. Following four days of stretching, the number of nascent fibres had
      increased in both strains but was significantly greater in HW than LW ALD muscle.
      The proliferation and differentiation capacities of satellite cells from HW and
      LW strains were investigated in culture. As judged by in vitro measurements of 3H
      thymidine incorporation and DNA content, satellite cells of HW turkey exhibited a
      greater proliferative capability than those of LW turkey. No differences in the
      temporal appearance of muscle markers (desmin, MHC isoforms) were noted in vitro
      between the two strains. These data confirm our in vivo observations indicating
      that selection based on growth rate does not modify muscle fibre maturation. Our
      in vivo and in vitro observations suggest that variations in the postnatal muscle
      growth pattern between HW and LW strains may be related to a difference in the
      capacity of their satellite cells to proliferate.

PMID- 9583368
TI  - Glutamine-supplemented total parenteral nutrition reduces blood mononuclear cell
      interleukin-8 release in severe acute pancreatitis.
AB  - Glutamine, a conditionally essential amino acid, is important for immune
      function. It is now being formulated for incorporation into total parenteral
      nutrition (TPN). The aims of this study were to examine the effect of glutamine
      administration on lymphocyte proliferation and proinflammatory cytokine release
      in patients with severe acute pancreatitis. Fourteen patients were randomized (in
      a double-blind fashion) to receive either conventional or isocaloric,
      isonitrogenous glutamine-supplemented (0.22 g glutamine x kg(-1) x d(-1) as
      glycyl-glutamine) TPN for 7 d. DNA synthesis (index of lymphocyte proliferation)
      and the 24-h release of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8
      from peripheral blood mononuclear cells were measured in vitro on days 0, 4, and
      7. Thirteen patients completed the study protocol (6 glutamine TPN, 7
      conventional TPN). Glutamine supplementation increased median DNA synthesis by
      3099 cpm over the study period against 219 cpm in the conventional group
      (increase not significantly different between the two groups) . Glutamine
      supplementation did not significantly influence TNF or IL-6 release, but, in
      contrast, median IL-8 release was reduced by day 7 in the glutamine group while
      it was increased in the conventional group (-17.7 ng/mL (median change over study
      period) versus +43.3 ng/mL, respectively; P=0.045). Small patient numbers and
      substantial interindividual variation limit the conclusions, but there is a trend
      for the glutamine group to have improved lymphocyte proliferation, and in the
      case of IL-8, reduced proinflammatory cytokine release.

PMID- 9583369
TI  - Dietary peptides improve wound healing following surgery.
AB  - To determine if peptide-based enteral diets improve wound healing when compared
      to amino acid-based diets, a prospective randomized study was conducted using 38
      male Sprague-Dawley rats. Following placement of a standardized abdominal wound,
      20 animals were randomized to an isonitrogenous peptide-based (PEP) versus amino
      acid-based diet (AA) for 10 d. In addition, 18 animals were randomized to an
      amino acid-based diet supplemented with the peptide carnosine (CARN) or its
      constituent amino acids (Control). Diets were administered through small bowel
      feeding tubes. Wound bursting pressure was significantly higher in the PEP
      animals compared to the AA animals (179+/-9 versus 138+/-12 mmHg; P=0.02). In
      addition, wound bursting pressure was significantly greater in the CARN animals
      compared to the Control animals (143+/-10 versus 116+/-8 mmHg; P=0.005). Peptide
      based enteral diets improve wound healing when compared to nonpeptide generating
      amino acid-based diets. We also conclude that the dietary peptide carnosine
      represents a dietary peptide that improves wound healing when administered as
      part of a complete enteral formula. This effect on wound healing may be
      clinically relevant because carnosine is not found in most enteral formulas.

PMID- 9583370
TI  - Nucleoside-nucleotide mixture increases bone marrow cell number and small
      intestinal RNA content in protein-deficient mice after an acute bacterial
      infection.
AB  - The aim of this study was to determine if intraperitoneal administration of a
      nucleoside-nucleotide mixture would affect small intestinal morphology, bone
      marrow cell number, and DNA content in protein-deficient mice subjected to acute
      bacterial infection. Mice were randomized into two groups and orally fed protein
      free diet or nucleotide-free 20% casein diet for 10 d. The mice in each group
      were divided into two subgroups and intraperitoneally administered 0.35 mL saline
      or nucleoside-nucleotide mixture (17.5 mL/kg body weight) for 10 d. On day 10,
      one subgroup from each major dietary group was either inoculated intravenously
      with methicillin-resistant Staphylococcus aureus or saline. Three days later,
      small intestinal morphology, bone marrow cell number, and DNA content were
      evaluated in infected and noninfected mice. Protein-deficiency in association
      with infection significantly (P < 0.05) reduced body weight, small intestinal
      weight, crypt depth, villous height, and wall thickness. All dietary groups
      exhibited similar small intestinal DNA and protein contents (protein:DNA ratio,
      RNA:DNA ratio) at 3 d postinfection. However, small intestinal RNA content in the
      infected protein-free dietary group administered nucleoside-nucleotide mixture
      was higher (P < 0.05) and tended to be higher relative to the infected nucleotide
      free 20% casein group administered nucleoside-nucleotide mixture compared with
      the rest of the groups. In the infected protein-free dietary group administered
      nucleoside-nucleotide mixture, bone marrow cell number and bone marrow DNA
      content were higher (P < 0.05) relative to the infected protein-free dietary
      group, nucleotide-free 20% casein diet administered saline, or nucleoside
      nucleotide mixture, respectively. We conclude that intraperitoneal administration
      of nucleoside-nucleotide mixture may stimulate bone marrow cell proliferation,
      DNA content, and small intestinal RNA content during periods of relative
      deficiency such as protein-deficiency in combination with infection.

PMID- 9583371
TI  - Effect of valine-depleted total parenteral nutrition on fatty liver development
      in tumor-bearing rats.
AB  - Valine-depleted amino acid imbalance, while having a suppressive effect on tumor
      growth, may induce fatty liver. We administered valine-depleted total parenteral
      nutrition (TPN) solution to rats subcutaneously transplanted with ascites
      containing hepatoma AH-109A and examined the time course of the development of
      fatty liver. An accumulation of fatty vacuoles was observed in hepatocytes on day
      4. To prevent the development of fatty liver in tumor-bearing rats, we
      administered a small amount of valine in addition to the valine-depleted
      imbalance solution via the central vein. Such treatment, however, resulted in
      neither the prevention of fatty liver development nor the suppression of tumor
      growth. To supply valine to the liver, we administered a low concentration of
      valine via the portal vein simultaneously with central venous administration of
      valine-depleted TPN solution. As a result, the peripheral blood valine level of
      these rats was < 0.5 that of the control group, but the valine in the liver was
      maintained at the same level as that of the control group, and accumulation of
      triacylglycerols in the liver was slight. However, the suppressive effect on
      tumor growth was maintained, as the tumor weight was suppressed to almost the
      same degree as that of rats administered only the valine-depleted solution.

PMID- 9583372
TI  - Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus
      ostreatus) in rats.
AB  - The effect of the dose of oyster mushroom in the diet (1.0, 2.5, and 5.0%) and of
      the period of application (8, 16, 28, and 52 wk) on cholesterol accumulation in
      blood and body organs was studied in weanling male Wistar rats fed a diet
      containing 0.3% cholesterol. Reduction of cholesterol in serum and body organs
      was found to be dependent on the amount of dietary oyster mushroom administered.
      A negative correlation between the mushroom dose and cholesterol level was found
      after 8 and 28 wk of feeding (r=-0.9821 and -0.9803, respectively; P < 0.02 for
      both cases). The dose of 1% oyster mushroom did not affect cholesterol levels in
      serum or body organs. A significant reduction of cholesterol levels was observed
      in serum (31-46%) and liver (25-30%) at a dose of 5% of oyster mushroom for all
      periods. Reduced cholesterol content in very low-density lipoproteins (VLDL) was
      also observed at this level. The highest dose of oyster mushroom induced a
      decrease in conjugated diene levels in erythrocytes and an increase in the levels
      of reduced glutathione in the liver and stimulated the activities of catalase and
      glutathione peroxidase in the liver in the final period of the experiment.

PMID- 9583373
TI  - Effect of an elemental diet on the mechanical resistance and morphology of the
      colon in rats.
AB  - The aim of this study was to investigate the effect of an elemental diet (ED) on
      colonic morphology and mechanical resistance. Rats received either laboratory
      chow (control group; n=6) or oral total parenteral nutrition solution (ED group;
      n=6). After 14 d the colon was measured and weighed with and without the
      contents. Bursting pressure was determined in the right and left colon. Samples
      of these segments were examined histologically. Crypt depth and wall width (WW)
      were measured. All animals gained body weight. The bowels of ED-fed animals were
      shorter (23.7+/-1.6 versus 19.7+/-1.8 cm; P=0.003) and weighed less than the
      controls either with (10.3+/-0.8 versus 5.0+/-0.7g, P < 0.001) or without (4.9+/
      0.9 versus 2.6+/-0.3 g; P < 0.001) feces. Bursting pressure was lower in animals
      receiving ED compared with controls (right colon: 250+/-30 versus 200+/-30 mm Hg;
      P=0.03; left colon: 195+/-22 versus 160+/-14 mm Hg; P=0.009). Crypt depth and WW
      were significantly shorter in the left colon in the ED group. Administration of
      ED promotes lack of mechanical resistance and atrophy of the colonic wall,
      especially in the left colon.

PMID- 9583374
TI  - Selenium and chromium deficiency during long-term home total parenteral nutrition
      in chronic idiopathic intestinal pseudoobstruction.

PMID- 9583375
TI  - Body composition measurement: a review of hydrodensitometry, anthropometry, and
      impedance methods.
AB  - Human body composition is an expression of genetic and nutritional factors. It
      can change as a consequence of exogenous influences such as training, disease, or
      diet and is therefore of particular interest to nutrition professionals. Two of
      the main methods of estimating body composition in this review (hydrodensitometry
      and anthropometry) have been in use for decades, but the third method
      (bioelectrical impedance) is more recent. The procedure, theoretical basis,
      assumptions, standard error of estimates, and comparisons with other techniques
      are presented for each of the three methods. References to general and specific
      populations are presented that illustrate regression equations for different
      ages, ethnic groups, and gender. The advantages and disadvantages of the three
      methods are reviewed with reference made to the alternative compartment models.
      Other methods (DEXA, infrared interactance) are briefly reviewed.

PMID- 9583376
TI  - Optimizing protein synthesis through enteral diets.

PMID- 9583377
TI  - Aluminum, tau protein, and Alzheimer's disease: an important link?

PMID- 9583378
TI  - Vitamin A deficiency and growth hormone in children.

PMID- 9583379
TI  - Long-chain fatty acids and cardiovascular disease risk in non-insulin-dependent
      diabetes.

PMID- 9583380
TI  - Outcome from nutritional support using hospital food.

PMID- 9583381
TI  - Creatine: a review of its nutritional applications in sport.

PMID- 9583382
TI  - Patient focused care: opportunities and implications.

PMID- 9583383
TI  - Standardization or age adjustment.

PMID- 9583384
TI  - Liberty or tyranny: the new health care Consumer Bill of Rights.

PMID- 9583385
TI  - Continuous pump-tube enteric hyperalimentation.

PMID- 9583386
TI  - Pediatric emergency medicine practice patterns: a comparison of pediatric and
      general emergency physicians.
AB  - OBJECTIVE: To determine whether differences exist between general emergency
      physicians (GEMs) and pediatric emergency physicians (PEMs) in the emergency care
      of children with common pediatric emergencies. METHODS: We carried out a survey
      study of all members of the American Academy of Pediatrics Section of Emergency
      Medicine and the Washington State American College of Emergency Physicians. We
      identified current therapeutic interventions for croup, asthma, bronchiolitis,
      seizures, febrile infant, conscious sedation, head trauma, and coin ingestion,
      and compared the practice patterns of GEMs and PEMs. RESULTS: A total of 66% of
      the surveys were returned, including 211 GEMs and 329 PEMs. The majority of PEMs
      practice in children's hospitals, whereas most GEMs practice in general community
      hospitals. Slightly over half (51%) of PEMs are PEM fellowship-trained versus 1%
      of GEMs. CROUP: The majority of GEMs and PEMs use racemic epinephrine (RE) in the
      treatment of a child with stridor at rest; approximately one-third admit to the
      hospital after RE (39 vs 30%, NS). PEMs are more likely to observe the child for
      >2 hours after RE (94% vs 79%, P < 0.01). The majority of PEMs and GEMs use
      steroids in these patients (94 vs 88%, NS). ASTHMA: There is no significant
      difference in the use of albuterol, aminophylline, or steroids. Steroids are more
      likely to be given orally by PEMs than GEMs (74 vs 50%, P < 0.01). BRONCHIOLITIS:
      The majority of both groups of physicians routinely use nebulized beta-agonists;
      however, significantly more GEMs than PEMs use steroids (68 vs 45 %, P < 0.01).
      SEIZURES: Half of GEMs vs 78% of PEMs use lorazepam as a first line drug in the
      treatment of seizures (P < 0.01). There is no significant difference with respect
      to the use of rectal diazepam in the pre-hospital setting. FEBRILE INFANT: GEMs
      are less likely than PEMs to admit the febrile infant <4 weeks of age (68 vs 87%;
      P < 0.01). Admission of older febrile infants (four to six weeks and eight weeks
      of age) is not significantly different between PEMs and GEMs. CONSCIOUS SEDATION:
      Both groups use a wide array of drugs alone or in combination to sedate children
      for complex facial laceration repair, closed fracture reduction, and cranial
      computed tomography (CT). GEMs are more likely to use ketamine for laceration
      repair (28 vs 16%, P < 0.01). Both GEMs and PEMs use midazolam plus a narcotic
      for fracture reduction. For further sedation for cranial CT, after an initial
      dose of midazolam, GEMs are more likely to use additional midazolam (64 vs 47%, P
      < 0.01), and PEMs are more likely to add pentobarbital (15 vs 4%, P < 0.01). HEAD
      TRAUMA: Most GEMs (87%) and PEMs (81%) would obtain a cranial CT on a
      neurologically normal two year old who had fallen down the stairs with a six
      minute loss of consciousness. COIN INGESTION: Most GEMs and PEMs would obtain
      radiographs on an asymptomatic two year old with a recent coin ingestion.
      CONCLUSION: With some notable exceptions, GEMs and PEMs have similar pediatric
      practice patterns despite differences in training and practice environments.

PMID- 9583387
TI  - Pediatric male rectal and genital trauma: accidental and nonaccidental injuries.
AB  - OBJECTIVE: To characterize accidental pediatric rectal/genital trauma in males
      and compare these physical findings to a cohort of boys evaluated for sexual
      abuse. DESIGN: Retrospective chart review. SETTING: Tertiary pediatric trauma
      center/sexual abuse clinic. PARTICIPANTS: Male patients evaluated in the
      emergency department for rectal/genital trauma from 9/1/89 through 10/31/93
      ("accidental group"). Male patients referred to Child Protection Services for
      suspected sexual abuse from 1/1/93 through 12/31/95 who had abnormal genital
      physical findings ("sexual abuse group"). MAIN OUTCOME MEASURES: Outcomes
      measured included age, mechanism of injury, category of diagnosis, location of
      injury, and type of injury. RESULTS: Forty-four male patients comprised the
      accidental group, aged six months to 17 years. The most common mechanism was a
      fall onto an object (34%). The most common injuries were lacerations/perforations
      of the scrotum (36%) followed by penile lacerations/perforations (25%). No
      patient had an isolated rectal laceration. Forty-four male patients with positive
      physical findings comprised the sexual abuse group. Ages ranged from seven months
      to 18 years. All patients had rectal lesions. Penile lacerations/perforations
      were the only other injuries documented, occurring in two patients. CONCLUSIONS:
      Accidental rectal/genital trauma in the pediatric population is uncommon; scrotal
      trauma occurs much more frequently than rectal trauma. Rectal/genital injury in
      the sexual abuse group typically involves only the rectal area. Sexual assault
      should be considered in patients with isolated rectal injury or whenever the
      alleged history does not correlate with physical findings.

PMID- 9583388
TI  - Sedation patterns in pediatric and general community hospital emergency
      departments.
AB  - BACKGROUND AND OBJECTIVES: Although pediatric sedation (PS) is widely used in
      emergency departments (ED), the practice of PS in general community hospital (GH)
      ED has not been described. We surveyed PS practice patterns in pediatric
      hospitals (CH) and GH and compared frequency and usage between the two groups.
      METHODS: All CH (n = 115) and 400 randomly selected GH were surveyed. Alcohol and
      drug detoxification, psychiatric, chronic care, rehabilitation, and specialty
      facilities were excluded. Data were collected on hospital type (pediatric or
      community), location (urban, suburban, rural), annual visits, academic
      affiliation (presence of an emergency medicine residency or pediatric emergency
      medicine fellowship in the hospital), and sedation agents used. RESULTS: Of 515
      hospitals surveyed, 238 responded [84/115 CH (73%), 154/400 GH (39%)] yielding an
      overall response rate of 46%. Of the responding CH the majority were urban [57
      (68%) were urban, 15 (18%) suburban, and 12 (14%) rural]. GH were more evenly
      distributed by location [44/153 (29%) were urban, 49/153 (32%) suburban, and
      60/153 (39%) rural]. Eight (5%) GH had emergency medicine residencies, while 39
      (46%) CH had pediatric emergency medicine fellowships. The mean annual pediatric
      volume was 38,000 for CH and 6500 for GH. For the four specified clinical
      scenarios, representing the most common ED procedures using sedation (laceration
      repair, fracture reduction, radiologic imaging), GH performed significantly fewer
      sedations than CH when matched for pediatric volume. PS was less frequently used
      among rural GH compared to suburban (P < 0.01) and urban GH (P < 0.01). Midazolam
      was listed as the most frequently used drug in all three geographic locations for
      both CH and GH. CH listed fentanyl as a second agent, while GH preferred
      meperidine. Fentanyl and ketamine were listed as preferred agents only in CH. For
      cranial computerized tomography, chloral hydrate was listed as the drug of choice
      by both CH and GH. Both CH and GH listed "relief of pain and anxiety" as the
      first and "agitation control" as the second most common reason for using
      sedation. CH and GH listed "the risks outweigh the benefits" as the primary
      reason and "ED too busy/takes too much time" as the secondary reason for not
      using sedation. CONCLUSIONS: GH performed fewer sedations than did CH when
      matched for pediatric volume in all geographic locations and for the most common
      ED procedures using sedation. Since 1989, sedation patterns have shifted in CH to
      include the short-acting agents, while GH (with the exception of midazolam)
      continue to prefer the long-acting agents. Midazolam is now the most frequently
      used sedation agent for ED procedures in both CH and GH.

PMID- 9583390
TI  - A streptococcal score card revisited.
AB  - OBJECTIVE: To evaluate the utility of a simple scoring system as a predictor of
      obtaining a positive throat culture for group A streptococci (GAS). DESIGN:
      Prospective descriptive study. Scores were assigned prior to the availability of
      the results of throat cultures. SETTING: Emergency department and walk-in clinic
      of the Children's Hospital of Pittsburgh. PATIENTS: Patients were 365 children
      between the ages of two and 16 years with acute onset of sore throat and a
      history of or documentation of fever within the preceding 24 hours.
      INTERVENTIONS: A streptococcal score was assigned on the basis of a 6-point
      schema in which the features were 1) age; 2) season; 3) temperature of at least
      38.3 degrees C; 4) adenopathy; 5) pharyngeal erythema, edema, or exudate; and 6)
      no symptoms of a viral upper respiratory infection (conjunctivitis, rhinorrhea,
      or cough). A throat culture was performed for the isolation of GAS. MAIN OUTCOME
      MEASURE: Positive predictive value of the streptococcal score in identifying
      children with a positive throat culture for GAS. RESULTS: A score of 5 or 6
      predicted a positive culture for GAS in 59 and 75% of children, respectively. In
      patients with evidence of acute pharyngitis, the combination of age between five
      and 15 years, fever and absence of upper respiratory symptoms predicted a
      positive culture for GAS in 72% of patients. CONCLUSIONS: The score can be used
      to predict the likelihood that a throat culture will be positive for GAS.

PMID- 9583389
TI  - Changes in treatment and outcomes of children receiving care in the intensive
      care unit for severe acute asthma.
AB  - OBJECTIVE: Significant changes have occurred in the intensity of treatment of
      children with severe asthma in the last decade. The objectives of this study are
      1) to describe the changes in treatment of asthmatic children needing care in the
      intensive care unit (ICU) initially treated in our emergency department (ED) in
      1983 to 1985 (I) and in 1990 to 1992 (II), and 2) to examine if these changes
      correspond to changes in clinical outcomes. DESIGN: Retrospective descriptive
      study. PATIENTS: All asthmatic children less than 18 years old treated in the ED
      and admitted to the ICU directly or via the ward with a primary diagnosis of
      asthma. SETTING: Pediatric tertiary care hospital. RESULTS: A total of 89 ICU
      admissions were required for patients initially treated in our ED, 54 in 1983 to
      1985 and 35 in 1990 to 1992. In 1985, 29.7% of asthma patients required hospital
      admission and 0.5% needed ICU admission, while 30.7 and 0.7% required hospital
      and ICU admission, respectively, in 1992. Admissions to the ICU directly via the
      ED were similar in both time periods (I, 27; II, 30), while those admitted to the
      ICU via the ward decreased significantly (I, 27; II, 5; P < 0.01). Recently,
      while in the ED, these ICU patients, on average, were treated with < or =q1h
      albuterol inhalations longer (I, 1.7 hours; II, 3.4 hours; P < 0.001), more
      frequently (I, 1.8 inhalations/h; II, 3.3 inhalations/h; P < 0.001), and with
      greater dosages (I, 0.20 mg/kg/h; II, 0.55 mg/kg/h; P < 0.001), than previously.
      Only 72% of patients in 1983 to 1985 received i.v. steroids in the ED versus 100%
      in 1990 to 1992. Ward patients in 1990 to 1992 received < or =q1h inhalations for
      a greater proportion of their ward stay (I, 6.9/14.7 hours = 47%; II, 9.2/9.2
      hours = 100%). There was a recent trend toward longer ICU treatment with < or
      =q1h albuterol inhalations (I, 8.7 hours; II, 12.3 hours; P = 0.24) and with i.v.
      albuterol (I, 29.4 hours; II, 37.4 hours; P = 0.26). Ventilation rates were low
      (I, 5/54 = 9.3%; II, 2/35 = 5.7%; P = NS) and the average duration of ICU stay
      remained unchanged (I, 40.6 hours; II, 42.1 hours; P = NS). CONCLUSIONS: Despite
      recent dramatic ED and ward treatment changes, ICU admission rates for pediatric
      asthma remain relatively constant. However, intensive treatment may have
      contributed to the decrease in ICU admissions via the ED to ward route in
      slightly less critical cases.

PMID- 9583391
TI  - The epidemiology of pediatric visits to New Jersey general emergency departments.
AB  - OBJECTIVE: To describe the epidemiology of pediatric visits to the emergency
      departments (EDs) of 10 general hospitals by age and gender. DESIGN: Review of
      ICD-9 codes from the billing database of a practice of emergency physicians.
      SETTING: Ten hospitals in north/central New Jersey. PATIENTS: All children <18
      years treated by group physicians in EDs of study hospitals. INTERVENTIONS: None.
      MAIN OUTCOME MEASURES: Diagnoses and visits. RESULTS: There were 319,430
      diagnoses recorded for 241,839 children (18.9% of the 1,277,233 total visits by
      all ages). The number of visits was highest in the <2 and >14 years age groups,
      with males predominating in all age groups. The number of visits from trauma
      increased with age. Otitis accounted for over 3% of all ED visits in this sample,
      over 7000 visits. CONCLUSIONS: Children account for a significant portion of ED
      visits in general hospitals. EDs need to be equipped and staffed to handle this
      clientele.

PMID- 9583392
TI  - The summer penile syndrome: seasonal acute hypersensitivity reaction caused by
      chigger bites on the penis.
AB  - OBJECTIVE: To describe the seasonal acute hypersensitivity reaction of the penis
      due to chigger bites, known as the summer penile syndrome. DESIGN: A consecutive
      series of patients. SETTING: The emergency department of an urban academic
      children's hospital in the midwestern United States. PARTICIPANTS: Male pediatric
      patients with an acute hypersensitivity reaction of the penis. RESULTS: Ninety
      four patients were treated for summer penile syndrome during the four-month
      period from June through September. Patients ranged in age from seven months to
      11 years (mean = 5.1, SD = 2.5). Twenty-one percent of patients had also
      experienced a similar prior episode of penile swelling. Symptoms included
      pruritus in 84% of cases, dysuria in 33%, and decreased strength of urine stream
      in 8% of patients. Eighty-four percent of patients had recent exposure to the
      woods, park, lawn, or poison ivy. In addition to edema, findings on physical
      examination included a papule or bite puncture mark in 50% of patients, erythema
      in 32%, and excoriation in 6% of patients. Fifty-six percent of patients had
      bites on other areas of the body. The emergency physician attributed the penile
      edema to an insect or chigger bite in 98% of cases. Treatment consisted of an
      oral antihistamine and cold compresses in most cases. The reported duration of
      penile swelling ranged from one to 18 days with a mean of 4.1 days (SD = 3.5),
      and the reported duration of pruritus ranged from 0 to 14 days with a mean of 3.0
      days (SD = 2.6). CONCLUSION: This study provides an understanding of the summer
      penile syndrome for pediatric care providers. To our knowledge, this study is the
      first to describe this seasonal syndrome in the medical literature.

PMID- 9583393
TI  - Saline with benzyl alcohol as intradermal anesthesia for intravenous line
      placement in children.
AB  - BACKGROUND: It has been suggested that saline with benzyl alcohol preservative
      has anesthetic properties when injected intradermally. We compared the pain
      associated with intravenous line (i.v.) placement in patients who received
      intradermal lidocaine, intradermal saline + benzyl alcohol preservative, or no
      anesthesia. METHODS: We performed a prospective randomized clinical trial in a
      convenience sample of children over 6.8 years old seen in the emergency
      department of a large, urban children's hospital. Children received either
      intradermal saline with 0.9% benzyl alcohol preservative, intradermal lidocaine,
      or no anesthesia prior to i.v. placement. The patient recorded the pain of the
      entire procedure on a visual analog scale. In the two groups that received an
      intradermal injection, the patient also recorded the pain of the first and second
      injection on a similar scale. RESULTS: Ninety-nine children were studied, 33 in
      each group. Pain scores were not normally distributed. The median pain scores in
      millimeters for the entire procedure were 41.0 (interquartile range, 11 to 62) in
      the nonanesthetic group, 9.0 (interquartile range 3 to 37) in the saline with
      benzyl alcohol group, and 10.0 (interquartile range, 4 to 32) in the lidocaine
      group (P = 0.006 for saline vs nonanesthetic, P = 0.04 for lidocaine vs
      nonanesthetic, P = 0.57 for saline vs lidocaine). There was no difference between
      groups with regard to baseline anxiety, demographic characteristics, size of i.v.
      inserted, number of i.v. attempts, or pain upon intradermal injection.
      CONCLUSION: Saline with benzyl alcohol and 1% lidocaine are equally effective as
      intradermal anesthetics for i.v. line placement in children, and are both more
      effective than no anesthesia.

PMID- 9583394
TI  - Local and topical anesthesia for pediatric wound repair: a review of selected
      aspects.

PMID- 9583395
TI  - Posterior sternoclavicular epiphyseal separation presenting with hoarseness: a
      case report and discussion.

PMID- 9583396
TI  - Esophageal obstruction after incomplete removal of a percutaneous endoscopic
      gastrostomy tube.
AB  - This two-year-old boy presented with a two-day history of vomiting and fever. He
      was diagnosed with acute otitis media four days before this incident. Repeated
      questioning revealed removal of a percutaneous enterostomy tube two weeks earlier
      with failure to pass the internal bumper in his stool. The child was in no
      distress, except for repeated emesis and drooling. A chest x-ray revealed a
      foreign body in the esophagus, and the patient underwent removal of the
      percutaneous endoscopic gastrostomy plastic bumper by endoscopy without incident.

PMID- 9583397
TI  - Successful treatment of dinitrophenol poisoning in a child.
AB  - BACKGROUND: Poisoning with agricultural toxins is well known in the adult
      environment, but is rarely seen in children. Vancouver, British Columbia, borders
      on a large agricultural area, and the British Columbia Children's Hospital is the
      provincial referral center for major pediatric emergencies. In our experience,
      children from farming communities are vulnerable to a range of agriculturally
      related injuries, and exposure to toxic chemicals requiring hospitalization is
      not rare. METHODS: This is a case report with literature review. RESULTS: A child
      presenting in a coma proved later to have been exposed to a toxic agent. The
      agent, dinitrophenol, is a widely used agricultural herbicide and insecticide.
      The diagnosis resulted from a detailed history and physical examination, which
      revealed symptoms and signs that suggested poisoning. A search of the farm
      resulted, and the parents located open dinitrophenol containers. The toxic
      effects of dinitrophenol described in adults by Poison Control matched those
      present in the child, and specific treatment interventions existed that could be
      implemented to positively influence outcome. CONCLUSIONS: Awareness of the
      possibility of exposure to dinitrophenol is required, as death can result from
      exposure, and milder cases may go unrecognized. Appropriate treatment can improve
      outcome. Injuries with toxic agricultural agents are wholly preventable if the
      materials are handled appropriately in the farm environment, and parents whose
      children live on or visit farms are aware of the risks involved and take
      appropriate precautions.

PMID- 9583399
TI  - Priapism: an unusual presentation of appendicitis.
AB  - Priapism, a persistent abnormal penile erection that is painful and unassociated
      with sexual interest, is known to be associated with a wide range of etiologies
      in children. This is a report of a case of appendicitis in an eight year old
      presenting with priapism. There is no mention in the pediatric literature of
      priapism associated with appendicitis. Possible appendicitis should be included
      in the differential diagnosis of priapism.

PMID- 9583398
TI  - Syphilis or abuse: making the diagnosis and understanding the implications.

PMID- 9583400
TI  - Hypokalemia in an asthmatic child from abuse of albuterol metered dose inhaler.
AB  - A case of albuterol abuse by a pediatric patient with the development of
      hypokalemia with electrocardiographic changes is presented. The hypokalemic
      effects of beta2-agonists are discussed in regard to the production of
      significant cardiac symptoms. Additionally, guidance regarding the evaluation of
      similar patients presenting in the emergency department is provided.

PMID- 9583401
TI  - Management of incomplete spontaneous abortion with suction curettage in the
      pediatric emergency department.
AB  - Pregnancy complications, including spontaneous abortion, are increasingly common
      reasons for teenage girls to seek medical care in pediatric emergency departments
      (EDs). A protocol was implemented in our department to identify patients with
      spontaneous abortion who would be candidates for outpatient management. We
      describe three cases of spontaneous abortion managed with suction curettage in
      our pediatric ED in collaboration with our obstetric/gynecologic colleagues.
      There are no reports in the pediatric literature regarding the role of suction
      curettage in the pediatric ED.

PMID- 9583402
TI  - Case 01-1998: a seven-year-old boy with anemia and fever.

PMID- 9583403
TI  - Periumbilical pain and fever.

PMID- 9583404
TI  - Pediatric emergency medicine: legal briefs.

PMID- 9583405
TI  - How aggressive the therapy?

PMID- 9583406
TI  - Toxicology reviews: fomepizole--a new antidote.

PMID- 9583407
TI  - Recent ketamine administration can produce a urine toxic screen which is falsely
      positive for phencyclidine.

PMID- 9583408
TI  - Case report and discussion of RLQ abdominal pain in an adolescent female.

PMID- 9583409
TI  - Electromagnetic fields and childhood leukemia.

PMID- 9583410
TI  - Body weight and mortality: what is the shape of the curve?

PMID- 9583411
TI  - Drinking water turbidity and gastrointestinal illness.

PMID- 9583412
TI  - Does maternal exposure to radiation before conception affect reproduction?

PMID- 9583413
TI  - How to change your mind.

PMID- 9583415
TI  - Body mass and 26-year risk of mortality from specific diseases among women who
      never smoked.
AB  - We examined the relation between Quetelet's body mass index (BMI) and age
      adjusted mortality risk from specific diseases in a 26-year prospective cohort
      study of 12,576 non-Hispanic white women who had never smoked. To account for
      effects due to antecedent disease, we focused on women surviving 15-26 years
      after their report of body weight. High BMI (>27 kg per m2) decreased the risk of
      fatal respiratory disease (hazard ratios of 0.7 for ages 30-54 years and 0.6 for
      ages 55-74 years) but increased risk in all other disease categories. Low BMI
      (<21 kg per m2) increased the risk of fatal respiratory disease (hazard ratios of
      2.0 for ages 30-54 years and 1.4 for ages 55-74 years). Among middle-aged women
      (ages 30-54 years), we found that low BMI also increased the risk of certain
      fatal cardiovascular diseases (hazard ratios of 1.5 for cerebrovascular death and
      2.5 for hypertensive and other cardiovascular deaths), but the increase in the
      risk of fatal cerebrovascular disease did not remain (hazard ratio of 0.4) after
      exclusion of subarachnoid and intraparenchymal hemorrhage deaths from the
      endpoint. Although the inverse relation between BMI and risk of fatal respiratory
      disease was also evident in the subset who reported body weight 17 years after
      baseline, further restriction of this subset to stable-weight women reporting no
      history of respiratory disease resulted in a U-shaped relation. Data from this
      subset also indicated that weight loss substantially increased the risk of fatal
      respiratory disease. These findings implicate high and low BMI as risk factors
      for fatal respiratory disease but suggest that the risk due to high BMI was
      obscured by weight loss that followed the onset of disease. The overall findings
      support an association between obesity and a higher risk of fatal disease but
      also raise the possibility that apparently healthy, never-smoking women can
      experience a higher long-term risk of fatal cardiovascular and respiratory
      diseases due to a lower body weight.

PMID- 9583414
TI  - Association between childhood acute lymphoblastic leukemia and use of electrical
      appliances during pregnancy and childhood.
AB  - As part of a comprehensive study of residential magnetic field exposure in nine
      midwestern and mid-Atlantic states, we evaluated the use of appliances by 640
      patients with acute lymphoblastic leukemia, 0-14 years of age, diagnosed between
      1989 and 1993, and 640 matched control children. Mothers were interviewed
      regarding use of electrical appliances during their pregnancy with the subject
      and the child's postnatal use. The risk of acute lymphoblastic leukemia was
      elevated in children whose mothers reported use of an electric blanket or
      mattress pad during pregnancy [odds ratio (OR) = 1.59; 95% confidence interval
      (CI) = 1.11-2.29] but was reduced for use of sewing machines during pregnancy (OR
      = 0.76; 95% CI = 0.59-0.98). The risk of acute lymphoblastic leukemia was
      increased with children's use of electric blankets or mattress pads (OR = 2.75;
      95% CI = 1.52-4.98) and three other electrical appliances (hair dryers, video
      machines in arcades, and video games connected to a television), but the patterns
      of risk for duration in years of use and frequency of use were inconsistent for
      most appliances used by children. Risks rose with increasing number of hours per
      day children spent watching television, but risks were similar regardless of the
      usual distance from the television. The inconsistency in the dose-response
      patterns for many appliances, reporting and selection bias, and the lack of an
      effect for measured 60 Hertz magnetic fields or wire codes in our companion study
      must be considered before ascribing these associations to exposures from magnetic
      fields.

PMID- 9583416
TI  - An analysis of the Milwaukee cryptosporidiosis outbreak based on a dynamic model
      of the infection process.
AB  - We combined information on the temporal pattern of disease incidence for the 1993
      cryptosporidiosis outbreak in Milwaukee with information on oocyst levels to
      obtain insight into the epidemic process. We constructed a dynamic process model
      of the epidemic with continuous population compartments using reasonable ranges
      for the possible distribution of the model parameters. We then explored which
      combinations of parameters were consistent with the observations. A poor fit of
      the March 1-22 portion of the time series suggested that a smaller outbreak
      occurred before the March 23 treatment failure, beginning sometime on or before
      March 1. This finding suggests that had surveillance systems detected the earlier
      outbreak, up to 85% of the cases might have been prevented. The same conclusion
      was obtained independent of the model by transforming the incidence time series
      data of Mac Kenzie et al. This transformation is based on a background monthly
      incidence rate for watery diarrhea in the Milwaukee area of 0.5%. Further
      analysis using the incidence data from the onset of the major outbreak, March 23,
      through the end of April, resulted in three inferred properties of the infection
      process: (1) the mean incubation period was likely to have been between 3 and 7
      days; (2) there was a necessary concurrent increase in Cryptospordium oocyst
      influent concentration and a decrease in treatment efficiency of the water; and
      (3) the variability of the dose-response function in the model did not
      appreciably affect the simulated outbreaks.

PMID- 9583417
TI  - Did Milwaukee experience waterborne cryptosporidiosis before the large documented
      outbreak in 1993?
AB  - The patterns of incidence and pathways of spread for cryptosporidiosis are poorly
      understood. In this study, we explored the possibility that drinking water caused
      significant waterborne cryptosporidiosis in Milwaukee well before the massive
      documented outbreak in April 1993. We generated time series of daily counts of
      emergency room visits and hospital admissions for gastroenteritis in Milwaukee
      using the billing records of the Medical College of Wisconsin for January 1,
      1992, through May 3, 1993. The Milwaukee Water Works provided us with data on
      drinking water turbidity for the same period. The service area of the South Plant
      experienced a sharp rise in turbidity just before the outbreak. During the
      outbreak period, gastroenteritis events were most strongly associated with
      turbidity at a lag of 7 days in children and 8 days in adults. It is reasonable
      to conclude that these lag times reflect the incubation period of
      Cryptosporidium. During the 434 days before the outbreak, gastroenteritis events
      were most strongly associated with turbidity at a lag of 8 days among children
      and 9 days among adults in the service area of the North Plant, the plant that
      experienced the highest effluent turbidity during this period. These findings are
      consistent with the conclusion that waterborne cryptosporidiosis was occurring in
      Milwaukee for more than a year before the documented outbreak.

PMID- 9583418
TI  - Adverse reproductive outcomes among women exposed to low levels of ionizing
      radiation from diagnostic radiography for adolescent idiopathic scoliosis.
AB  - In a cohort of women followed up for adolescent idiopathic scoliosis, we assessed
      the association between exposure to ionizing radiation from diagnostic
      radiography received in adolescence and subsequent adverse reproductive outcomes
      in adulthood. We estimated risk for unsuccessful attempts at pregnancy,
      spontaneous abortions, low birthweight (<2,500 gm), congenital malformations, and
      stillbirths according to dose to the ovaries. We used regression models for
      binary and continuous outcomes, accounting for key covariates and for clustering
      in the data that arose from women having multiple pregnancies. Risks in the
      adolescent idiopathic scoliosis cohort were higher than in the reference group
      for unsuccessful attempts at pregnancy [adjusted odds ratio (OR) = 1.33; 95%
      confidence interval (CI) = 0.84-2.13], spontaneous abortions (OR = 1.35; 95% CI =
      1.06-1.73), and congenital malformations (OR = 1.20; 95% CI = 0.78-1.84), but the
      odds ratios did not increase monotonically by dose to the ovaries. There were
      fewer stillbirths (OR = 0.38; 95% CI = 0.15-0.97) and low-birthweight infants in
      the adolescent idiopathic scoliosis cohort (OR = 0.84; 95% CI = 0.59-1.21).
      Nevertheless, when the analysis of low birthweight was restricted to the
      adolescent idiopathic scoliosis cohort, the adjusted odds ratios were found to
      increase by quartiles of dose (median dose of 0.69 cGy): 1; 1.43 (95% CI = 0.54
      3.90); 2.24 (95% CI = 0.89-5.94); and 2.34 (95% CI = 1.02-5.62). We also found
      that the adjusted mean birthweight decreased with increasing dose by 37.6 gm per
      cGy (standard error = 23.5 gm per cGy). Associations between adverse reproductive
      outcomes and radiotherapy have been observed previously, but this is the first
      study in which an association with birthweight has been found with diagnostic
      radiography.

PMID- 9583419
TI  - Risk factors for preterm birth subtypes.
AB  - To assess epidemiologic risk factors for preterm birth subcategories in an urban
      population, we undertook a study of 31,107 singleton livebirths that took place
      at Mount Sinai Hospital in New York City between 1986 and 1994. We subdivided the
      preterm births into preterm premature rupture of the membranes, preterm labor,
      and medically induced births. We obtained information regarding the preterm
      subtypes and their epidemiologic risk factors from a computerized perinatal
      database. Adjusted odds ratios showed an increased risk for all three preterm
      birth subtypes in women who were black (1.9 for preterm premature rupture of
      membranes, 2.1 for preterm labor, and 1.7 for medically induced births) or
      Hispanic (1.7 for preterm premature rupture of membranes, 1.9 for preterm labor,
      and 1.6 for medically induced births), those who had had a previous preterm birth
      (3.2 for preterm premature rupture of membranes, 4.5 for preterm labor, and 3.3
      for medically induced births), those who began prenatal care after the first
      trimester ( 1.4 for preterm premature rupture of membranes, 1.3 for preterm
      labor, and 1.3 for medically induced births), women who had been exposed to
      diethylstilbestrol in utero (3.1 for preterm premature rupture of membranes, 4.1
      for preterm labor, and 3.7 for medically induced births), patients with
      preexisting diabetes mellitus (2.2 for preterm premature rupture of membranes,
      2.4 for preterm labor, and 9.5 for medically induced births), and those with
      antepartum bleeding (2.8 for preterm premature rupture of membranes, 3.6 for
      preterm labor, and 3.7 for medically induced births). Other sociodemographic,
      constitutional, life-style, and obstetrical characteristics differed across the
      groups. Variation in some of the risk factors among the preterm subtypes implies
      that epidemiologic assessment of the more specific outcomes would be advisable.

PMID- 9583420
TI  - African-American mothers' perception of their residential environment, stressful
      life events, and very low birthweight.
AB  - We performed a hospital-based case-control study of African-American mothers to
      explore the relation between a mother's perception of her own residential
      environment and very low birthweight. We administered a structured questionnaire
      to mothers of very-low-birthweight (<1,500 gm; N = 28) and critically ill non-low
      birthweight (>2,500 gm; N = 52) infants. The groups had similar sociodemographic
      characteristics. The vast majority of participants were unmarried and had no
      private medical insurance. The odds ratios of very low birthweight fluctuated
      between 1.7 and 3.2 for African-American mothers who rated their neighborhoods
      (in terms of police protection, protection of property, personal safety,
      friendliness, delivery of municipal services, cleanliness, quietness, and
      schools) unfavorably. Additionally, the odds ratio of very low birthweight for
      mothers exposed to three or more stressful life events during pregnancy was 3.1
      (95% confidence interval = 1.2-8.2). We conclude that African-American mothers'
      perception of their residential environment and frequency of stressful life
      events are associated with very low birthweight in their infants.

PMID- 9583421
TI  - A hospital-based case-control study of stillbirths and environmental exposure to
      arsenic using an atmospheric dispersion model linked to a geographical
      information system.
AB  - Although adverse reproductive outcomes have been associated with arsenic
      exposure, the extent and severity of the effects of chronic inhalation of low
      levels of arsenic on reproduction are not known. We conducted a hospital-based
      case-control study of stillbirths in a central Texas community that included a
      facility with more than a 60-year history of producing primarily arsenic-based
      agricultural products. We collected data on 119 cases and 267 controls randomly
      selected from healthy live-births at the same hospital and matched for year of
      birth. We abstracted medical and demographic data for the period January 1, 1983,
      to December 31, 1993, from hospital records and estimated socioeconomic status by
      median income from the 1990 Population and Housing Census data. We estimated
      arsenic exposure levels from airborne emission estimates and an atmospheric
      dispersion model and linked the results to a geographical information system
      (GIS) database. Exposure was linked by GIS to residential address at time of
      delivery. A conditional logistic regression model was fitted including maternal
      age, race/ethnicity, parity, income group, exposure as a categorical variable,
      and exposure-race/ethnicity interaction. The prevalence odds ratio observed for
      Hispanics in the high-exposure group (>100 ng per m3 arsenic) was 8.4, with a 95%
      confidence interval of 1.4-50.1.

PMID- 9583422
TI  - Oral contraceptive use and risk of colorectal cancer.
AB  - To evaluate the relation between oral contraceptives and colon and rectal cancer,
      we analyzed combined data from two case-control studies conducted in six Italian
      regions between 1985 and 1996. The studies included 803 women with incident colon
      cancer, 429 with rectal cancer, and 2,793 controls with acute, nonneoplastic,
      nondigestive, non-hormone-related disorders. We estimated odds ratios (ORs) and
      95% confidence intervals (CIs) from unconditional multiple logistic regression
      equations, including terms for age, center/study period, education, family
      history of colorectal cancer, menopausal status, age at menopause, parity, use of
      hormone replacement therapy, body mass index [weight (kg) per height squared
      (m2)], and total energy intake. Ever-use of oral contraceptives was inversely
      associated with colon cancer (OR = 0.63; 95% CI = 0.45-0.87) and rectal cancer
      (OR = 0.66; 95% CI = 0.43-1.01). Duration of use of oral contraceptives was
      inversely related to risk of colon but not rectal cancer. This study suggests
      that women who have ever used oral contraceptives are at lower risk of colon and
      rectal cancer.

PMID- 9583423
TI  - Environmental tobacco smoke and lung cancer in nonsmokers: does time since
      exposure play a role?
AB  - We conducted a population-based case-control study in Stockholm during 1989-1995
      to investigate the risk of lung cancer from exposure to environmental tobacco
      smoke. The study base consisted of persons above 30 years of age resident in
      Stockholm County who had never smoked regularly (that is, one cigarette or more
      daily for 1 year). Cases of lung cancer were identified at the three major county
      hospitals responsible for diagnosis and treatment of lung cancer. A total of 124
      cases (35 men and 89 women) and 235 population controls (72 men and 163 women)
      participated. The never-smoking status was validated by interviews with next-of
      kin. The relative risk associated with ever-cohabiting with a smoking spouse was
      1.2 [95% confidence interval (CI) = 0.7-1.9]. Ever-exposure at work to
      environmental tobacco smoke carried a relative risk of 1.6 (95% CI = 0.9-2.9).
      Risks tended to be more elevated in high-exposure groups and with recent
      exposures. Both sources of environmental tobacco smoke seemed important, and
      considerable misclassification of total exposure occurred for each variable used
      separately, in particular for the less common spousal exposure. For those
      currently exposed to environmental tobacco smoke from the spouse, at work, or
      both, the relative risk was 2.6 (95% CI = 1.0-6.5). Our data imply that
      information from major sources of environmental tobacco smoke should be combined
      to avoid important misclassification and that timing of exposure should also be
      taken into consideration.

PMID- 9583424
TI  - Controlling confounding when studying large pharmacoepidemiologic databases: a
      case study of the two-stage sampling design.
AB  - Large drug databases have been the source of interesting developments for
      pharmacoepidemiologic research, because they provide relatively accurate drug
      exposure histories. An important limitation of these databases is the lack of
      information on potential confounders. One solution, developed more than a decade
      ago but not widely used, is "two-stage sampling," in which stage 1 is the
      collection of information on drug exposure and outcomes, and stage 2 is the
      collection of confounder data on a subset of the stage 1 sample. The balanced
      design, wherein an equal number of individuals is selected from each drug
      exposure/disease category, is usually the most efficient strategy by which to
      select the stage 2 sample. We illustrate the efficiency of the balanced design in
      two-stage sampling using data from a provincial health organization and a
      simulation. We also evaluate the relative importance of factors affecting the
      precision of the effect estimate of the exposure of interest.

PMID- 9583425
TI  - Serum ascorbic acid and cardiovascular disease prevalence in U.S. adults.
AB  - To examine the relation between serum ascorbic acid level and the prevalence of
      cardiovascular disease, we analyzed data from 6,624 U.S. men and women enrolled
      in the Second National Health and Nutrition Examination Survey. We calculated
      odds ratios and 95% confidence intervals to estimate the relative prevalence of
      cardiovascular disease, defined as self-reported coronary heart disease or
      stroke, or a diagnosis of peripheral vascular disease based on physical
      examination. Serum ascorbic acid levels were independently associated with
      prevalence of coronary heart disease and stroke; a 0.5-mg per dl increase in
      serum ascorbic acid level was associated with an 11% reduction in coronary heart
      disease and stroke prevalence. We also analyzed the relation of ascorbic acid,
      grouped into low to marginal, normal, and saturation serum categories, to
      cardiovascular disease. Compared with participants with low to marginally low
      serum ascorbic acid levels, we found a 27% decreased prevalence of coronary heart
      disease (95% confidence interval = 10-41%) and a 26% decreased prevalence of
      stroke (95% confidence interval = 3-44%) among participants in the highest serum
      ascorbic acid category. Serum ascorbic acid levels were not consistently
      associated with prevalence of peripheral vascular disease. These results are
      consistent with the hypothesis that increased ascorbic acid intake may decrease
      the risk of coronary heart disease and stroke.

PMID- 9583426
TI  - Probability logic and probabilistic induction.
AB  - This article reviews some philosophical aspects of probability and describes how
      probability logic can give precise meanings to the concepts of inductive support,
      corroboration, refutation, and related notions, as well as provide a foundation
      for logically sound statistical inference. Probability logic also provides a
      basis for recognizing prior distributions as an integral component of statistical
      analysis, rather than the current misleading practice of pretending that
      statistics applied to observational data are objective. This basis is important,
      because the use of realistic priors in a statistical analysis can yield more
      stringent tests of hypotheses and more accurate estimates than conventional
      procedures.

PMID- 9583427
TI  - Role of different types of vegetables and fruit in the prevention of cancer of
      the colon, rectum, and breast.
AB  - We compared the effect of 26 types or groups of vegetables and fruit on the risk
      of cancer using data from two case-control studies that included 1,225 cases of
      cancer of the colon, 728 cases of cancer of the rectum, 2,569 cases of cancer of
      the breast, and 5,155 hospital controls interviewed between 1991 and 1996 in six
      Italian areas. Most vegetables were inversely associated with cancer of the colon
      and rectum, whereas only carrots and raw vegetables lowered breast cancer risk.
      High fruit intake was associated only with a reduction of rectal cancer.
      Different contents of sugar, fiber, carotenoids, and folic acid in fruits vs
      vegetables plus the concurrent consumption of oil with vegetables may partly
      explain these findings.

PMID- 9583428
TI  - Incidence of diagnosed carpal tunnel syndrome in a general population.
AB  - We sought to determine the incidence rate of carpal tunnel syndrome in the
      general population. Using three different case definitions, we conducted a
      prospective study to ascertain by medical record review all cases of incident
      disease in a defined population during a 2-year period. Newly diagnosed probable
      or definite carpal tunnel syndrome (N = 309) occurred at a rate of 3.46 cases per
      1,000 person-years (95% confidence interval = 3.07-3.84). The incidence rate in
      our study was 3.5 times higher than the rate 20 years ago in a Minnesota city.
      The rate difference probably results from a combination of reasons, including a
      true rise in incidence.

PMID- 9583430
TI  - The future of genetic studies of complex human diseases: an epidemiologic
      perspective.

PMID- 9583429
TI  - Combined effect of smoking and human papillomavirus type 16 infection in cervical
      carcinogenesis.
AB  - To study the combined effect of smoking and human papillomavirus (HPV) type 16
      infection in high-grade cervical intraepithelial neoplasia, we analyzed data from
      a Norwegian population-based case-control study including 90 patients and 216
      controls, 20-44 years of age. We assessed HPV-16 status both by polymerase chain
      reaction detecting virus DNA and by enzyme-linked immunosorbent assay detecting
      antibodies against virus capsid. Smoking was associated with cervical
      intraepithelial neoplasia grade II-III in HPV-16-positive individuals. Using the
      jointly unexposed (HPV-16 DNA-negative never-smokers) as the reference group, we
      determined the risk of cervical intraepithelial neoplasia grade II-III in HPV-16
      DNA-positive never-smokers and HPV-16 DNA-positive ever-smokers (odds ratio =
      15.7; 95% confidence limits = 3.2, 76.5, and odds ratio = 65.9; 95% confidence
      limits = 22.3, 194.3, respectively). The estimated proportion of cases among HPV
      16-positive smokers that is attributable to the interaction between the two
      causes is 74%, based on HPV-16 DNA positivity.

PMID- 9583431
TI  - Oceanography and the seventh cholera pandemic.

PMID- 9583432
TI  - Drinking water and reproductive outcomes.

PMID- 9583433
TI  - Dioxin and diabetes mellitus.

PMID- 9583434
TI  - Dioxin and diabetes mellitus.

PMID- 9583435
TI  - Modeling temporal aspects of an exposure.

PMID- 9583436
TI  - Modeling temporal aspects of an exposure.

PMID- 9583437
TI  - Accounting for pregnancy dependence in epidemiologic studies of pregnancy
      outcomes.

PMID- 9583438
TI  - Epidemiology and the Internet.

PMID- 9583439
TI  - Relationship between normalization of negative T waves on exercise ECG and
      residual myocardial viability in patients with previous myocardial infarction and
      no post-infarction angina.
AB  - The usefulness of normalization of negative T waves in exercise ECG was
      investigated as an index of myocardial viability in patients with previous
      myocardial infarction with no symptoms or ischemic ST-segment change during
      exercise test. A total of 39 patients, 20 with T-wave normalization (POS group)
      and 19 without T-wave normalization (NEG group) on exercise ECG. were studied.
      Myocardial viability was evaluated by thallium-201 single-photon emission
      computed tomography (SPECT) during exercise or at rest. We also assessed left
      ventricular ejection fraction (LVEF) by contrast ventriculography before (n=39)
      and after percutaneous transluminal coronary angioplasty (PTCA) (n=17). SPECT
      detected myocardial viability in 16 (80%) of the 20 patients in the POS group and
      in 4 (21%) of the 19 patients in the NEG group (p<0.01). LVEF increased after
      successful PTCA in the POS group (from 53+/-13% to 63+/-8%, p<0.025), but fell in
      the NEG group (from 57+/-10% to 51+/-8%). It is concluded that normalization of
      negative T waves on exercise ECG is a useful, simple index of myocardial
      viability in patients with previous myocardial infarction with no symptoms or
      ischemic ST-segment change during exercise testing.

PMID- 9583440
TI  - Redistribution in thallium-201 myocardial imaging soon after successful coronary
      stenting--tomographic evaluation during coronary hyperemia induced by adenosine.
AB  - To evaluate the clinical significance of reversible perfusion defects that were
      observed soon after the successful deployment of a coronary stent, 47 patients
      underwent thallium-201 myocardial scintigraphy and radionuclide angiography in
      conjunction with adenosine-induced coronary hyperemia before and after complete
      revascularization. Coronary angiography showed a significant decrease in the
      percent diameter stenosis (from 87+/-11% before stenting to -1+/-5% after
      stenting, p<0.01) with no major dissection, residual stenosis, or intra-stent
      formation of thrombus. Even after the angiographically successful procedure,
      reversible perfusion defects were present in 17 (36%) of the 47 patients, none of
      whom showed any wall motion abnormalities during the infusion of adenosine.
      Disease duration was significantly longer and collateral vessels were more common
      in the patients with than in those without thallium redistribution, whereas the
      other clinical, pre- and post-stent angiographic and hemodynamic factors were
      similar. In conclusion, reversible perfusion defects without wall motion
      abnormalities were demonstrated during the infusion of adenosine in approximately
      one-third of patients soon after coronary stenting, and were not consistently
      related to acute unfavorable outcomes of stent placement.

PMID- 9583441
TI  - Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by
      iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and
      its relation to exercise-induced ischemia.
AB  - Reversible thallium-201 (201Tl) abnormalities during exercise stress have been
      used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and
      are most likely to identify relatively underperfused myocardium. Although
      metabolic abnormalities in HCM were reported, the relationship between impaired
      energy metabolism and exercise-induced ischemia has not been fully elucidated as
      yet. To assess the relationship between myocardial perfusion abnormalities and
      fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise 201Tl
      and rest 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy.
      Perfusion abnormalities were observed by exercise 201Tl in 19/28 patients with
      HCM. 123I-BMIPP uptake was decreased compared with delayed 201Tl in 106/364 (29%)
      of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity
      between 123I-BMIPP and 201Tl was observed more often in the 49/75 (65%) segments
      with reversible exercise 201Tl defects (p<0.001). Our results indicate that
      exercise-induced myocardial ischemia exists in HCM, resulting in metabolic
      abnormalities. The combination of 123I BMIPP and 201Tl suggests that myocardial
      ischemia may play an important role in metabolic abnormalities in HCM.

PMID- 9583442
TI  - Effect of mental stress on hemodynamics and left ventricular diastolic function
      in patients with ischemic heart disease.
AB  - Mental stress is an important factor affecting cardiac function. We evaluated the
      effect of a mental calculation stress (MS) test on hemodynamics and left
      ventricular (LV) diastolic function in patients with ischemic heart disease, and
      compared the hemodynamic responses with a treadmill exercise test. Fifteen
      patients were studied. Seven had old myocardial infarction with significant
      coronary artery stenosis (group I) and 8 had chest pain syndrome with non
      significant coronary artery stenosis (group II). The MS test was performed as
      follows: after memorizing 6 random numeral digits, patients repeated these
      numbers in reverse order for 5 min followed by serial subtraction of 1000 minus
      17 for 5 min. Blood pressure (BP) and heart rate (HR) were measured every 1-5
      min. Doppler mitral flow velocity (MFV) was recorded every 2-5 min. During the MS
      test, BP, HR, and rate pressure product increased by 38.3%, 17.3%, and 62.1% on
      average, respectively. Early diastolic MFV decreased by 10.0% in group I and 3.3%
      in group 11. First third filling rate of MFV decreased by 32.3% in group I and
      22.8% in group II. A/E ratio increased by 39.3% in group I and 25.8% in group II.
      These data indicate that the MS test led to a deterioration in LV diastolic
      function. The MS test induced LV diastolic dysfunction to a greater extent in
      patients with significant coronary artery stenosis than in those without
      significant coronary stenosis. Myocardial ischemia may be induced by increased
      left ventricular afterload and/or vasoconstrictive reflex of coronary
      microcirculation.

PMID- 9583443
TI  - Comparison of filled-in myocardial segments after early and late reinjection of
      thallium-201--influence of the timing of reinjection on fill-in.
AB  - Thallium-201 (201Tl) late reinjection after stress-redistribution imaging
      improves the detection of viable myocardium. Recently, early reinjection of 201Tl
      immediately after stress imaging was proposed as a new method for distinguishing
      ischemic myocardium, hibernating myocardium, and myocardial scar. However, there
      are no data on the influence of the timing of reinjection on "fill-in." This
      study was designed to assess whether the reinjection time influences "fill-in" in
      chronic coronary artery disease. Thirty-three patients with chronic coronary
      artery disease were studied. All patients underwent exercise 201Tl tomography.
      Immediately after stress imaging, 37 MBq of thallium was reinjected earlier than
      usual and early reinjection delayed image (ERDI) was acquired 3 h later. With the
      same protocol, all patients also underwent a second study involving late
      reinjection of 201Tl within 1 week. An additional 37 MBq of thallium was
      reinjected 3 h after stress imaging, and late reinjection delayed image (LRDI)
      was obtained 10 min later. All images were analyzed qualitatively using a 4-point
      grading uptake score. Of the 72 hypoperfused segments on stress images, 66
      segments showed fill-in and 6 showed persistent defects on ERDI, and of the same
      72 segments 55 segments displayed fill-in and the remaining 17 showed persistent
      defects on LRDI (p<0.05). The delta uptake score (the uptake score of the delayed
      image minus that of stress image) in early reinjection was 1.60+/-0.80, which was
      significantly higher than that in late reinjection (1.24+/-0.94, p<0.01). A small
      dose of thallium reinjected immediately after stress imaging with delayed images
      obtained 3 h later is convenient and might provide another technique for
      determining myocardial viability.

PMID- 9583444
TI  - Cardioprotective effect of intravenous nicorandil in patients with successful
      reperfusion for acute myocardial infarction.
AB  - This study was designed to assess the cardioprotective effect of intravenous
      nicorandil, a potassium channel opener, in preventing reperfusion injury in acute
      myocardial infarction. Seventy patients were treated with placebo or nicorandil
      concomitant with reperfusion therapy in a prospective, randomized, double-blind
      fashion within 6 h after the onset of acute myocardial infarction. Nicorandil was
      administered before reperfusion as a 2-mg bolus iv injection followed by
      continuous infusion of 2-6 mg/h for the next 3 h. Thirty-six patients (17 in the
      placebo group, 19 in the nicorandil group) who demonstrated both complete
      occlusion of an infarct-related vessel before treatment and successful
      reperfusion were included in the final analysis. No significant changes in left
      ventricular ejection fraction were observed between the immediate and chronic
      phases in each group. In the analysis of regional ventricular function, the
      placebo group did not show any significant change in regional chord shortening
      (26.8+/-8.2 vs 24.3+/-7.3%, NS) or hypocontractile perimeter (36.4+/-28.2% vs
      28.3+/-24.8%, NS) between immediate and chronic phase left ventriculograms. In
      contrast, in the nicorandil group, a significant increase in regional chord
      shortening (21.5+/-11.0% vs 25.8+/-11.3%, p<0.05) and a significant decrease in
      hypocontractile perimeter (33.3+/-19.6% vs 25.6+/-24.3%, p<0.05) were observed in
      the chronic phase left ventriculogram. Thus, nicorandil may be a useful
      adjunctive therapy for preserving myocardial contractile function in patients
      with acute myocardial infarction undergoing reperfusion therapy.

PMID- 9583445
TI  - Circadian and septadian variation in the occurrence of acute myocardial
      infarction in a Chinese population.
AB  - To investigate whether circadian or any other temporal pattern(s) exist in the
      occurrence of acute myocardial infarction (AMI) in a Chinese population, we
      analyzed 428 patients with confirmed AMI for temporal patterns of AMI occurrence.
      The patients admitted to the Affiliated Hospital of Shandong Medical University
      during 1991-95 were from Jinan, the capital city of Shandong Province of China,
      which has a population of 2.5 million. The chi-square test for goodness of fit
      was used to test the difference among the frequencies of AMI occurrence in 4
      equal intervals (01.00-07.00 h, 07.00-13.00 h, 13.00-19.00 h, 19.00-01.00 h)
      during the day and among those on 7 days during the week. The results showed that
      AMI occurrence exhibited significant circadian (p<0.001) and septadian (day of
      the week) (p=0.046) periodicity, with a peak at 01.00-07.00 h and a trough at
      13.00-19.00 h during the day, and a peak on Saturday and a trough on Wednesday
      during the week. The peak to trough ratio of risk was 2.7 during the day and 2.1
      during the week. It is concluded that there were circadian and septadian
      biorhythms in AMI occurrence in the Chinese population and that these were
      different from those observed in Western populations. Further investigation of
      the underlying mechanisms may shed further light on the trigger mechanisms of AMI
      and thus be helpful in the prevention and treatment of AMI.

PMID- 9583446
TI  - Plasma thromboxane B2 concentration in patients with ventricular septal defect
      and pulmonary hypertension.
AB  - Plasma thromboxane B2 (TXB2)-a stable metabolite of thromboxane A2 (TXA2)
      conventional hemodynamic parameters, mean pulmonary input energy (input energy),
      and mean pulmonary output energy (output energy) were measured to assess platelet
      activation in 21 patients with pulmonary hypertension and a ventricular septal
      defect (VSD). The patients were divided into 2 groups: group A (normal range) and
      group B (high level). TXB2 levels were measured by radioimmunoassay. There was no
      relationship between plasma TXB2 concentrations and conventional hemodynamic
      parameters except the pulmonary-to-systemic pressure ratio. Output-to-input
      energy ratio was correlated logarithmically with the plasma TXB2 concentration.
      We concluded that patients with output/input energy ratio >0.15 had a high TXB2
      concentration and activated platelets in pulmonary capillaries.

PMID- 9583447
TI  - Virtualized angioscopy of the thoracic aorta in a rabbit model of
      atherosclerosis.
AB  - The purpose of this study was to apply virtual reality technology to spiral
      computed tomographic (CT) angiogram images in a rabbit model of atherosclerosis
      and to correlate the images with histopathologic evaluation of the aorta. Image
      data were transferred to the virtual endoscope system in a graphics workstation.
      "Virtualized angioscopy" includes an interactive graphic user interface, which
      controls the viewpoint, the direction of the observation, and rendering and
      navigation functions. The virtual angioscopy system demonstrated irregularities
      of the luminal surface of the ascending aorta and a smooth luminal surface in the
      descending aorta. These observations were correlated with histopathologic
      findings. The results of this study indicate that the potential and real benefits
      of virtualized angioscopy far outweigh several technical limitations.

PMID- 9583448
TI  - Varying types of circus movement re-entry with both normal and dissociated
      contralateral conduction causing different right and left atrial rhythms in
      canine atrial flutter.
AB  - The purpose of this study was to develop an animal model of atrial flutter (AFL)
      or fibrillation (AFB) and to determine precisely the pathway of atrial activation
      during arrhythmias induced by programmed stimulation. In 10 dogs, a shunt from
      the left subclavian artery to the left upper pulmonary vein was created to
      produce left atrial enlargement. Five months later, using programmed electrical
      stimulation, it was possible to induce 17 sustained atrial tachycardias in 9 of
      the 10 dogs, including 9 episodes of AFL caused by circus movement re-entry, 6
      episodes of focal tachycardia, and 2 episodes of AFB. Short cycle length left
      atrial tachycardias caused by either circus movement or a focus did not propagate
      in a uniform 1:1 pattern to the right atrium (RA), resulting in RA dissociation.
      In these arrhythmias, complex wavefronts from both current and preceding left
      atrial cycles coexisted in the RA. Circus movement was associated with a spectrum
      of different re-entrant pathways with different path lengths. These differences
      in the path length were determined by various ways in which obstacles such as the
      superior vena cava and orifice of the right atrial appendage or pulmonary vein
      orifices were combined by contiguous areas of functional block.

PMID- 9583449
TI  - Recovery from complete atrioventricular block caused by idiopathic giant cell
      myocarditis after corticosteroid therapy.
AB  - Giant cell myocarditis (GCM) is a rapidly progressive disease that leads to
      ventricular tachycardia or high-grade atrioventricular (A-V) block, frequently
      requiring a pacemaker. A 64-year-old woman developed syncope as a result of
      idiopathic GCM with A-V block. She required both a temporary and a permanent
      pacemaker. Two-dimensional echocardiography showed severely reduced wall motion.
      There was no histologic or clinical evidence to suggest sarcoidosis. Despite
      treatment with diuretics and an angiotensin-converting enzyme inhibitor,
      exertional dyspnea persisted. She received prednisolone 4 months after the onset
      of complete A-V block in the late phase of GCM. Prednisolone improved A-V nodal
      conduction in spite of the fact that there was no influence from LV wall motion,
      and sinus rhythm has continued for more than 2 years. In this patient,
      prednisolone was effective in the treatment of GCM.

PMID- 9583451
TI  - Magnetic resonance imaging of Bland-White-Garland syndrome--a case of anomalous
      origin of the left coronary artery from the pulmonary trunk in a 22-year-old
      woman.
AB  - Selective right coronary angiography in a 22-year-old woman demonstrated an
      enormous right coronary artery, with the contrast medium opacifying to the left
      coronary artery through a well-developed collateral circulation and draining into
      the pulmonary artery. The diagnosis of anomalous origin of the left coronary
      artery from the pulmonary trunk [also known as Bland-White-Garland (BWG)
      syndrome] was thus established. Magnetic resonance imaging (MRI) showed a dilated
      right coronary artery arising from the aorta, the left coronary artery from the
      pulmonary trunk but not from the aorta, and well-developed channels in the
      interventricular septum. MRI could be a useful tool for diagnosing anomalous
      origin of the left coronary artery from the pulmonary trunk.

PMID- 9583450
TI  - Dynamics of QT interval in a patient with long QT syndrome and a normal QT
      interval.
AB  - A case report of a 15-year-old girl who experienced syncope and torsades de
      pointes is presented. The girl had a normal QT interval (QTc=0.37 sec) on the
      resting electrocardiogram (ECG). Infusion of isoproterenol induced QT
      prolongation (QTc=0.62 sec) and frequent occurrence of multiform ventricular
      premature beats. Her Holter ECG showed a prolongation of the QTc interval with a
      shortening of the RR interval. Low-frequency power (LF) and high-frequency power
      (HF) of heart rate variability were evaluated from the Holter ECG. The patient
      showed a statistically significant negative QTc/HF and a significant positive
      QTc/(LF/HF) relationship, whereas none of the age- and sex-matched healthy
      subjects showed these relationships. The slope of the QT/RR relationship for the
      patient was below the lower limit of the normal range. This report describes the
      unusual relationship of QT interval to RR interval and heart rate variability in
      a long QT syndrome patient with a normal QT interval on resting ECG.

PMID- 9583452
TI  - An elderly man with Klinefelter syndrome associated with hypertrophic
      cardiomyopathy, sick sinus syndrome, and coronary arteriovenous fistula.
AB  - Hypertrophic cardiomyopathy (HCM) is a rare cardiac complication in patients with
      Klinefelter syndrome. We report the case of a 67-year-old Japanese man with
      Klinefelter syndrome, HCM, sick sinus syndrome, and coronary arteriovenous
      fistula, in whom the 47XXY/46XY mosaic pattern was revealed by chromosomal study.
      Echocardiography revealed HCM with an interventricular septum thickness of 17 mm
      and a left ventricular posterior wall thickness of 10 mm. Sick sinus syndrome
      type III was diagnosed by paroxysmal atrial fibrillation (longest sinus arrest
      9.0 sec) on 24-h Holter ECG recording. Coronary arteriovenous fistula was
      detected from the left anterior descending artery to the right ventricle by
      coronary arteriography. To our knowledge, this is the first case report of
      Klinefelter syndrome with HCM. As there have been a few reports of patients with
      Klinefelter syndrome in association with skeletal muscular diseases such as
      Becker-type muscular dystrophy or myotonic dystrophy, the gene mutation that
      causes Klinefelter syndrome may occur in the cardiac muscle. HCM may represent
      another variable expression of this chromosomal abnormality.

PMID- 9583453
TI  - Astemizole-induced torsades de pointes in a patient with vasospastic angina.
AB  - Astemizole (Hismanal), an antihistamine agent, has been reported to be associated
      with ventricular arrhythmias. In this paper we present a case of QT prolongation
      and torsades de pointes (TdP) in a 77-year-old woman who had been taking
      astemizole (10 mg/day) for 6 months because of allergic skin disease. At the time
      of admission, the serum concentration of astemizole and its metabolites was
      markedly elevated at 15.85 ng/ml, approximately 3 times the normal level. The
      patient was also taking cimetidine, a known inhibitor of cytochrome P-450
      enzymatic activity, and during her admission was diagnosed as having vasospastic
      angina. To the best of our knowledge, this is the first report of astemizole
      induced QT prolongation and TdP in Japan.

PMID- 9583454
TI  - Aortic regurgitation in a patient with primary antiphospholipid syndrome--a case
      report.
AB  - We present the case of a 39-year-old woman with aortic regurgitation that may
      have been induced by primary antiphospholipid syndrome. The patient had suffered
      recurrent miscarriages, thrombocytopenia, and deep-vein thrombosis for the
      previous 16 years, and had been diagnosed as having primary antiphospholipid
      syndrome 9 years previously because of a high titer of anticardiolipin antibody.
      She had been receiving medication for moderate hypertension for 7 years. The
      patient was admitted to Tenri Hospital because of heart failure, which was
      thought to be caused by moderate aortic regurgitation, moderate hypertension, and
      mild chronic renal failure. Echocardiography revealed thickened aortic and mitral
      valves. Primary antiphospholipid syndrome might have induced valve regurgitation
      as a result of valvular thickening.

PMID- 9583455
TI  - The clinical impact of platelet glycoprotein IIb/IIIa receptor blockade in
      cardiovascular medicine.
AB  - Several of the adverse events that occur in acute coronary syndromes and after
      percutaneous coronary revascularization procedures are believed to be mediated by
      platelets. Recently, using molecular biology techniques, the platelet
      glycoprotein IIb/IIIa receptor was identified as the final common pathway for
      platelet aggregation. Thus, blocking the action of this receptor would seem to be
      an attractive proposition for reducing ischemic complications. A monoclonal
      antibody was the first agent in this new pharmacological family to be designed,
      but several peptide and peptide-like substances have subsequently been developed.
      This paper reviews the development of this class of agents and the various
      preclinical and clinical trials that have been undertaken. Early studies
      evaluated such agents during percutaneous coronary revascularization procedures.
      Because of the overwhelming benefits observed in such patients, together with the
      current limitations of treatments for acute coronary syndromes, the scope of
      investigations has been extended. Preliminary reports have been encouraging.

PMID- 9583456
TI  - Aortic valve replacement with a small mechanical valve prosthesis--a clinical and
      echocardiographic study of a St Jude Medical valve prosthesis.
AB  - The use of small aortic valve prostheses raises concerns about harmful effects of
      residual obstruction to left ventricular outflow. The present study was
      undertaken to examine long-term clinical and echocardiographic results in 193
      patients who underwent isolated aortic valve replacement (AVR) with a St Jude
      Medical (SJM) valve of 25 mm or smaller. The study subjects comprised 128 male
      and 65 female patients with a mean age of 54.1 years. The patients were divided
      into 2 groups according to the size of the valve prosthesis used for AVR. Small
      valves (19 or 21 mm) were implanted in 49 patients (group S) and large valves (23
      or 25 mm) were used in 144 patients (group L). The group S patients were mainly
      female, older, and had smaller body surface areas. There were no significant
      differences in early and late mortality in group S as compared with group L.
      Furthermore, there was no difference in the incidence of valve-related or
      cardiac, non-valve-related death, including the incidence of sudden death,
      between the 2 groups, and they enjoy a similar level of daily routine activity
      regardless of the valve size used. Left ventricular (LV) function (ejection
      fraction, fractional shortening, LV mass index, LV end-systolic volume index, and
      LV end-diastolic volume index) measured by echocardiography improved
      significantly and returned to normal values after AVR in both groups. Moreover,
      no significant differences were observed in the postoperative variables of the LV
      function. These results suggest that 19-mm and 21-mm SJM valves can be safely
      used for AVR in the majority of Japanese patients.

PMID- 9583457
TI  - Diagnostic approach in exercise testing to detect a significant narrowing of the
      left anterior descending coronary artery in inferior vs posterior myocardial
      infarction.
AB  - To detect a significant narrowing of the left anterior descending artery in
      patients with inferior/posterior myocardial infarction, 200 patients underwent
      standard exercise testing. Age, gender, and grade of stenosis of the left
      anterior descending artery were similar in 138 patients with inferior myocardial
      infarction and 62 with posterior myocardial infarction. In patients with left
      anterior descending artery stenosis, there were more lateral leads with ST
      segment depression (1.8+/-1.0 vs 1.1+/-1.1; p<0.01) and fewer anterior leads with
      ST-segment depression (2.1+/-1.4 vs 2.9+/-1.4; p=0.02) in those with inferior
      myocardial infarction than in those with posterior myocardial infarction.
      Applying the criterion of exercise-induced ST-segment depression > or = 0.1 mV,
      sensitivities and specificities in detecting left anterior descending artery
      stenosis were 98% and 21% respectively in inferior myocardial infarction and 94%
      and 26% respectively in posterior myocardial infarction. In contrast,
      discriminant analysis revealed sensitivities and specificities of 77% and 91%
      respectively in inferior myocardial infarction and 71% and 81% respectively in
      posterior myocardial infarction using the variables related to severity of
      inducible ischemia and lateral and anterior lead ST-segment depression. These
      results indicate that a multivariate approach underscoring the site of myocardial
      infarction can help in identifying stenosis of the left anterior descending
      artery in patients with inferior/posterior myocardial infarction.

PMID- 9583458
TI  - Thromboembolic complication in atrial fibrillation in a long-term follow-up--the
      relationship with underlying disease, type of atrial fibrillation, and
      antithrombotic therapy.
AB  - The incidence of thromboembolic complications among 288 patients with atrial
      fibrillation (AF) who were followed up during an average period of 7.2 years was
      examined retrospectively. The annual incidence of thromboembolic complications
      was 1.6% in total, 1.7% in valvular heart disease (n=128), and 2.1% in non
      valvular heart disease (n=117). No thromboembolism occurred in lone AF (n=43),
      defined as the complete absence of any underlying disease. The type of AF before
      embolic attack was chronic in 26 cases and paroxysmal in 6 cases. The cardiac
      rhythm at the time of the embolic attack was AF, except in 2 cases in which ECG
      was not recorded. In all patients with thromboembolic complications who were
      receiving antithrombotic therapy during the follow-up, the anticoagulant effect
      just before the embolic attack was found to be insufficient. Major bleeding was
      not observed in the patients receiving antithrombotic therapy. Thromboembolism in
      AF in long-term follow-up tends to occur more frequently in patients with
      underlying heart disease and in those with chronic AF compared rather than
      paroxysmal AF; it rarely occurs in lone AF. We should not hesitate to administer
      sufficient anticoagulant therapy in AF patients who are at high risk of
      developing thromboembolic complications.

PMID- 9583459
TI  - Glycated hemoglobin levels and their correlation with atherosclerotic risk
      factors in a Japanese population--the Jichi Medical School Cohort Study 1993
      1995.
AB  - We conducted a large population-based study to assess levels of glycated
      hemoglobin A1c (HbA1c) and to evaluate the correlation between HbA1c and other
      cardiovascular risk factors in Japan. A total of 910 men and 1,890 women aged 30
      69 years participated in the Jichi Medical School Cohort Study (1993-95). Mean
      HbA1c was 5.61% in men and 5.49% in women. HbA1c levels were significantly
      correlated with levels of triglycerides, fibrinogen, and factor VII, and
      inversely correlated with high-density lipoprotein (HDL)-cholesterol level in
      both sexes. Lipoprotein(a) was inversely correlated in men. Blood pressure, body
      mass index (BMI), and total cholesterol were significantly associated with HbA1c
      in women. After adjusting for significant variables in univariate analyses,
      fibrinogen and factor VII remained as significant correlates in men, and BMI and
      total cholesterol in women. The authors conclude that HbA1c level is correlated
      not only with classical cardiovascular risk factors, but also with fibrinogen and
      factor VII. Our results suggest that HbA1c could be an alternative to blood
      glucose in evaluating atherosclerotic risk in a large-sized population study.

PMID- 9583460
TI  - Effects of class I and III antiarrhythmic drugs on ventricular tachycardia
      interrupting critical paced cycle length with rapid pacing.
AB  - The most common mechanism of sustained ventricular tachycardia (VT) is re-entry
      with an excitable gap, but the electrophysiologic properties and response to
      antiarrhythmic drugs in the area of slow conduction are not yet fully known. The
      purpose of this study was to assess the effects of a class I antiarrhythmic drug
      (procainamide) and class III agents (amiodarone, E-4031, and MS-551) on re
      entrant VT using the width of the zone of entrainment. The cycle length (CL) of
      VT (VTCL), the block CL that was the longest paced CL that interrupted the VT,
      and the width of the zone of entrainment, defined as the difference between VTCL
      and block CL, were compared before and after treatment with antiarrhythmic drugs.
      The VTCL was prolonged significantly from 308+/-63 to 410+/-77 msec after
      procainamide (p<0.005) but was not changed after the administration of the class
      III agents: from 294+/-50 to 292+/-13 msec after amiodarone, and from 305+/-47 to
      313+/-31 msec after E-4031 or MS-551 (p=NS). The block CL was prolonged from
      255+/-61 to 331+/-70 msec after procainamide (p <0.01), from 256+/-20 to 260+/-25
      msec after amiodarone, and unchanged after E-4031 or MS-551 (253+/-31 msec before
      and 270+/-43 msec after) (p=NS). The width of the zone of entrainment as a
      representative of the width of the excitable gap was changed from 52+/-26 to 79+/
      35 msec (p<0.05) after procainamide, whereas it was unchanged after amiodarone
      (48+/-7 msec before and 43+/-7 msec after) and after E-4031 or MS-551 (50+/-10
      msec before and 40+/-9 msec after). Therefore, amiodarone, E-4031, and MS-551 did
      not affect VTCL and block CL whereas procainamide increased these parameters. The
      excitable gap substituting as the zone of entrainment was increased by
      procainamide but slightly reduced by amiodarone, E-4031, and MS-551. The effects
      of these antiarrhythmic drugs on the excitable gap of re-entrant VT were variable
      and should be examined further.

PMID- 9583462
TI  - Correlation between initial potentials on a signal-averaged P-wave and indice of
      electrophysiologic measurements in the right atrium.
AB  - The aim of this study was to determine whether initial potentials of the P-wave
      on a signal-averaged electrocardiogram (SAE) during sinus rhythm reflect indices
      of electrophysiologic measurements in the high lateral right atrium. A total of
      67 patients underwent P-wave signal averaging during electrophysiologic testing.
      The correlation between root mean square voltages for the initial 10 and 20 msec
      of the P-wave on the SAE and indices of electrophysiologic measurements, sinus
      node recovery time (SRT) and sinoatrial conduction time (SACT), obtained from
      programmed stimuli, was evaluated. It was found that the initial potentials of
      the P-wave on the SAE correlated negatively with SRT and SACT (-0.37 < or = r <
      or = -0.30). It was concluded that the initial potentials correlated with indices
      of electrophysiologic measurements, although the statistical significance was
      weak.

PMID- 9583461
TI  - Dipyridamole thallium-201 single-photon emission computed tomography for
      prediction of perioperative cardiac events in patients with arteriosclerosis
      obliterans undergoing vascular surgery.
AB  - The aim of the study was to determine whether or not dipyridamole thallium-201
      single-photon emission computed tomography (201Tl-SPECT) has significant additive
      value for predicting perioperative cardiac events in patients with
      arteriosclerosis obliterans (ASO) undergoing vascular surgery. Routine
      preoperative 201Tl-SPECT was performed in 106 consecutive patients with ASO (age
      68+/-8.9 years; 91 men and 15 women). The frequency of reversible defects in a
      clinical high-risk group (n=44) was significantly higher than in a low-risk group
      (n=62; 55% vs 24%, p<0.01). Perioperative cardiac events occurred in 9 patients,
      including 4 cardiac deaths, 1 non-fatal myocardial infarction, and 4 cases of
      unstable angina. Although clinical risk stratification was useful in predicting
      cardiac events (19% in the high-risk group vs 2% in the low-risk group, p<0.01),
      the positive predictive value was low. When considering a combination of 2 or
      more than 2 risk factors and a large reversible defect as a predictor, the
      positive predictive value and specificity increased from 19% to 47% and from 64%
      to 91%, respectively, whereas the sensitivity remained unchanged (89%). These
      results suggest that the addition of 201Tl-SPECT data to clinical risk-stratified
      patients with ASO allows better prediction of perioperative cardiac events.

PMID- 9583463
TI  - Familial evidence of vasospastic angina and possible involvement of HLA-DR2 in
      susceptibility to coronary spasm.
AB  - An association between genetic factors and susceptibility to coronary spasm has
      not been proven. Because we encountered 7 patients with familial occurrence of
      vasospastic angina (VSA) in 3 families, the association of a genetic factor with
      coronary spasm was assumed. HLA typing as one of the genetic markers was
      performed in the 3 families, and the affected members in each family were found
      to share a HLA haplotype, carrying both HLA-DR52 and DQ6. This raised the
      possibility that one of the susceptibility genes for coronary spasm is located in
      the HLA region. To assess this possibility, HLA typing was performed and compared
      in 110 patients with VSA but without a family history of VSA (VSA group) and 55
      patients with chest pain syndrome (CPS group) as control subjects. All patients
      underwent a provocation test for coronary spasm, and spasm was angiographically
      documented in the VSA group but not in the CPS group. Of all HLA antigens, the
      frequency of only HLA-DR2 was significantly higher in the VSA group than in the
      CPS group (39.1% vs 18.2%, p<0.01). The result implied that HLA-DR2 is in linkage
      disequilibrium with a susceptibility gene of VSA and thus is possibly involved in
      susceptibility to coronary spasm in some patients with VSA.

PMID- 9583464
TI  - Atrial conduction curves in patients with and without atrial fibrillation.
AB  - In order to quantify underlying atrial conduction properties in patients with
      atrial fibrillation (AF) using clinical electrophysiology techniques, atrial
      conduction curves relating intra-atrial conduction times to extrastimulus
      prematurities during programmed atrial stimulation were drawn. Based on the
      presence or absence of AF episodes, 95 subjects were divided into 2 groups:
      control (n=42); and AF (n=53). During programmed stimulation introduced from the
      right atrial appendage, an atrial conduction curve was drawn for each patient.
      For most of the control subjects, when the extrastimulus prematurity was
      increased by 10-ms steps, the intra-atrial conduction times also increased
      gradually; the maximum stepwise prolongation in intra-atrial conduction time was
      11.0+/-3.4 msec. For patients with AF, a 10-msec increase in extrastimulus
      prematurity often produced a sudden marked prolongation in the intra-atrial
      conduction time; the maximum stepwise prolongation of intra-atrial conduction
      time was 21.4+/-5.9 msec. In contrast to the gradual atrial conduction curves
      recorded in control subjects, the sudden prolongation of intra-atrial conduction
      time was remarkable on the curves obtained in patients with AF. Statistical
      significance was clearly established (p<0.0001). This difference could be related
      to differences in the underlying conduction properties in patients with and
      without AF.

PMID- 9583465
TI  - Myocardial salvage by reperfusion 12 hours after coronary ligation in dogs.
AB  - It is not clear why late reperfusion therapy in patients with acute myocardial
      infarction is effective. An investigation was carried out as to whether or not
      reperfusion conducted 12 h after coronary occlusion causes myocardial salvage in
      dogs. Coronary arteries were occluded in 11 mongrel dogs and a portion of the
      occlusion (late reperfusion area; LR area) reperfused 12 h later; the other part
      was left occluded (permanent occlusion area; PO area). The dogs were maintained
      for 4 weeks after reperfusion. Regional myocardial blood flow (Qm) was measured
      by the non-radioactive colored microsphere method. In both areas, the
      transmurality of necrosis was measured by triphenyl tetrazolium chloride
      staining, and the amount of viable myocardium and the extent of fibrosis was
      determined by Azan-Mallory staining. Qm decreased markedly after coronary
      occlusion to similar levels in both areas until 12 h. Qm transiently increased in
      the LR area only following reperfusion after 12 h. The transmurality of necrosis
      in the PO area was 83.8+/-10.5%, but that in the LR area was 58.7+/-21.3%, a
      significant decrease (p<0.01). In the outer layer, the amount of viable
      myocardium was significantly greater, and the extent of myocardial fibrosis was
      significantly less in the LR area. Evaluation in the same heart of dogs confirmed
      the myocardial salvage effects of late reperfusion (12 h after coronary
      occlusion).

PMID- 9583466
TI  - Local delivery infusion pressure is a key determinant of vascular damage and
      intimal thickening.
AB  - Local drug delivery following percutaneous transluminal coronary angioplasty
      (PTCA) may prevent restenosis by achieving higher local tissue concentrations of
      drugs than systemic administration. However, it remains unknown whether vascular
      damage and the ensuing intimal thickening is associated with the degree of
      infusion pressure achieved by local delivery. Therefore, local delivery of normal
      saline was performed using a channeled balloon catheter (Transport) to the rabbit
      iliac artery with different infusion pressures of 0, 3, 5, 7, and 12 atm (n=4 for
      each). The extent of vascular damage and the development of intimal thickening
      were determined histopathologically 14 days after the procedure. In 10 additional
      rabbits, to assess the degree of vessel penetration, local delivery of
      indocyanine green dye solution was performed in a similar fashion. After 1 h, the
      green dye penetrated deeply at the higher infusion pressures of 7 and 12 atm. The
      incidence of internal clastic lamina laceration and occurrence of total occlusion
      as a result of thrombus formation demonstrated an increase proportional to the
      degree of local infusion pressure. When the vascular injury score in each
      arterial section was plotted against the infusion pressure, a significant
      relation was observed (r=0.717, p<0.0001). At 0, 3, 5, 7, and 12 atm, neointimal
      areas of 0.160+/-0.005, 0.163+/-0.008, 0.189+/-0.017, 0.260+/-0.027, and 0.329+/
      0.033 mm2, respectively, were observed. Smooth muscle cell (SMC) proliferative
      activity also increased in proportion to the local infusion pressure. We have
      demonstrated for the first time that local delivery infusion pressure itself is
      related to the severity of vascular damage, resulting in the development of
      intimal thickening and an associated increase in SMC proliferative activity.
      Therefore, we suggest that infusion pressure is a key determinant of vascular
      injury during local drug delivery, with lower pressure causing the least
      neointimal response.

PMID- 9583467
TI  - A case report of myolysis during high-dose amiodarone therapy for uncontrolled
      ventricular tachycardia.
AB  - We report a rare case of a 41-year-old male patient, a professional musician,
      with dilated cardiomyopathy and sustained ventricular tachycardia (VT) that was
      refractory to class I antiarrhythmic drugs. Severe myolysis developed after 10
      months' administration of amiodarone (400 mg/day) in combination with mexiletine
      (300 mg/day) and disopyramide (400 mg/day). He had been suffering from severe
      moving muscle pain and an extremely high (16,830) IU/ml) serum level of creatine
      kinase (CK). The dosage of amiodarone was reduced from 400 mg/day to 200 mg/day
      without reduction of mexiletine or disopyramide and the patient's symptoms
      diminished. However, sustained VT developed, and so the dosage of the drug was
      increased to 250 mg/day. The high serum level of CK also decreased and returned
      to the normal range after the reduction in amiodarone dosage. Electrophysiologic
      examination of moving muscle revealed normal motor and sensory conduction
      velocities and, furthermore, the electromyogram revealed normal potentials and
      normal motor units. We conclude that severe myolysis developed as a result of the
      high dose and chronic administration of amiodarone. This is the first report of a
      Japanese patient showing rare and serious adverse effects in response to
      amiodarone treatment.

PMID- 9583468
TI  - Diabetes mellitus and cardiomyopathy--association with mutation in the
      mitochondrial tRNA(Leu)(UUR) gene.
AB  - In this report, cardiac abnormalities in 2 diabetic patients with a mutation in
      the mitochondrial tRNA(Leu)(UUR)gene are described. The 2 patients exhibited left
      ventricular dilation and diffuse decreased wall motion. Cardiac catheterization
      studies revealed normal coronary angiography. In both patients, light microscopic
      examination of hematoxylin and eosin-stained sections revealed myocyte
      hypertrophy and perinuclear vacuolization and electron microscopy revealed an
      increase in the number and size of mitochondria and abnormal configuration of
      cristae. These findings suggest that mutations in mitochondrial DNA, such as an A
      ->G mutation at position 3243, should be considered as a cause not only of
      diabetes mellitus but also of cardiac involvement in patients with diabetes
      mellitus.

PMID- 9583469
TI  - Circulating hepatocyte growth factor as an early marker of arterial thrombus
      formation.
AB  - This study was designed to measure circulating hepatocyte growth factor (HGF) in
      a rat model of arterial thrombosis. The carotid endothelial surface of rats was
      denuded with a balloon catheter and partially occluded. The amount of thrombus
      formation was expressed as the difference between the wet weights of paired
      treated and nontreated carotid arteries. Thrombus weight increased gradually up
      to 60 min after denudation. Plasma HGF did not increase before 30 min, but had
      significantly increased by 60 min compared with all previous measurements
      (p<0.05). Measurements of circulating HGF may be useful in the early diagnosis of
      arterial thrombosis.

PMID- 9583470
TI  - Studies in cranial suture biology: up-regulation of transforming growth factor
      beta1 and basic fibroblast growth factor mRNA correlates with posterior frontal
      cranial suture fusion in the rat.
AB  - The mechanisms involved in normal cranial suture development and fusion as well
      as in the pathophysiology of craniosyostosis are not well understood. The purpose
      of this study was to investigate the expression of several cytokines-
      transforming growth factor-beta-1 (TGF-beta1), basic fibroblast growth factor
      (bFGF), and interleukin-6 (IL-6)--during cranial suture fusion. TGF-beta exists
      in three mammalian isoforms that are abundant in bone and stimulate calvarial
      bone formation when delivered locally. Other bone growth factors including basic
      fibroblast growth factor and the interleukins regulate bone growth and are
      mitogenic for bone marrow cells and osteoblasts. The involvement of growth
      factors in the pathophysiology of craniosynostosis is supported by recent
      genetics data linking fibroblast growth factor receptor mutations to syndromal
      craniosynostoses. In this experimental study, in situ hybridization was used to
      localize and quantify the gene expression of TGF-beta1, bFGF, and IL-6 during
      cranial suture fusion. In the Sprague-Dawley rat, the posterior frontal cranial
      suture normally undergoes fusion between 12 and 22 days of age, whereas all other
      cranial sutures remain patent. All in situ analyses of fusing posterior frontal
      sutures were compared with the patent, control, sagittal sutures. Posterior
      frontal and sagittal sutures, together with underlying dura, were harvested from
      rats at 8, 12, 16, and 35 days of postnatal life to analyze posterior frontal
      suture activity before, during, and after fusion. In situ hybridization was
      performed on frozen sections of these specimens using DNA probes specific for TGF
      beta1, bFGF, and IL-6 mRNA. A negative control probe to IL-6 in the sense
      orientation was also used to validate the procedure. Cells expressing cytokine
      specific mRNA were quantified (in cells positive per 10(-1) mm2) and analyzed
      using the unpaired Student's t test. Areas encompassing the fibrous suture and
      the surrounding bone plates were analyzed for cellular mRNA activity. IL-6 mRNA
      expression showed a minimal rise in the posterior frontal suture at days 12 and
      16, with an average count of 10 and 6 cells per 10(-1) mm2, respectively. The
      sagittal suture remained negative for IL-6 mRNA at all time points. TGF-beta1 and
      bFGF analyses were most interesting, showing marked increases specifically in the
      posterior frontal suture during the time of active suture fusion. On postnatal
      day 8, a 1.5-fold increase in posterior frontal suture TGF-beta1 mRNA was found
      compared with sagittal sutures (p = 0.1890, unpaired Student's t test). This
      difference was increased 26-fold on day 12 in posterior frontal suture TGF-beta1
      expression (p = 0.0005). By day 35, posterior frontal suture TGF-beta1 mRNA had
      nearly returned to prefusion levels, whereas TGF-beta1 mRNA levels in the
      sagittal suture remained low. A similar upregulation of bFGF mRNA, peaking at day
      12, was observed in posterior frontal but not sagittal sutures (p = 0.0003).
      Furthermore, both TGF-beta1 and bFGF mRNA samples with intact dura showed an
      intense dural mRNA expression in the time preceding and during active posterior
      frontal suture fusion but not in sagittal tissues. Our data demonstrate that TGF
      beta1 and bFGF mRNA are up-regulated in cranial suture fusion, possibly signaling
      in a paracrine fashion from dura to suture. TGF-beta1 and bFGF gene expression
      were dramatically increased both in and surrounding the actively fusing suture
      and followed the direction of fusion from endocranial to epicranial. These
      experimental data on bone growth factors support the recent human genetics data
      linking growth factor/fibroblast growth factor receptor deletions to syndromal
      craniosynostoses. The ultimate aim of these studies is to understand the
      underlying mechanisms regulating suture growth, development, and fusion so
      surgeons may one day manipulate the biology of premature cranial suture fusion.

PMID- 9583471
TI  - Studies in cranial suture biology: regional dura mater determines overlying
      suture biology.
AB  - The influence of dura mater on adjacent cranial sutures is significant. By better
      understanding the mechanisms of normal suture fusion and the role of the dura
      mater, it may be possible to delineate the events responsible for the premature
      suture fusion seen in craniosynostosis. In the Sprague-Dawley rat, the posterior
      frontal suture normally fuses between 12 and 20 days of postnatal life and has
      proved to be an excellent model to describe normal suture fusion. The purpose of
      this study was to document the critical role that the dura mater-suture complex
      may play on cranial suture biology. Forty Sprague-Dawley rats at 8 days of age
      were divided into two groups of 20 animals each. The control group (group A) had
      surgical disruption of the dura mater-calvarial interface. This was accomplished
      by elevating a strip of cranium inclusive of the posterior frontal and sagittal
      sutures and replacement of the cranial strip back to its anatomic position, all
      with the dura mater left intact. The experimental group (group B) had the same
      calvarial elevation (strip craniectomy), but the sutural anatomy/alignment was
      rotated 180 degrees. This rotation placed the posterior frontal suture into the
      sagittal suture's anatomic position and the sagittal suture into the posterior
      frontal suture's anatomic position. All of these procedures were accomplished by
      leaving the underlying dura mater intact. Animals were killed at 20, 30, 40, and
      50 days (12, 22, 32, and 42 days postoperatively), and tissue sections were
      examined with hematoxylin and eosin staining. Group A (control) showed normal but
      delayed suture activity. The posterior frontal suture fused, and the sagittal
      suture remained patent. Fusion was delayed, not beginning before 20 days (12 days
      postoperative) and showing complete fusion between 30 and 40 days. Group B (180
      degree calvarial rotation) demonstrated that the suture in the posterior frontal
      anatomic position (actual sagittal suture) fused between 20 and 40 days, whereas
      the suture in the sagittal anatomic position (actual posterior-frontal suture)
      remained patent throughout the study. This study demonstrates that the location
      of the dura mater-suture complex is important in determining either suture
      patency or closure in this model. Normal closure of the suture overlying the
      posterior frontal dura mater demonstrates that the dura mater itself, or forces
      derived in specific cranial locations, determines the overlying suture biology.

PMID- 9583472
TI  - A model for the cleft lip nasal deformity.
AB  - The underlying pathology of the cleft lip nasal deformity has yet to be fully
      realized, and cleft lip rhinoplasty continues to challenge the reconstructive
      surgeon. A new model is proposed, which is composed of elements that represent
      known anatomical structures of the nose. These structures are considered
      elemental to the mechanism of the primary cleft lip nasal deformity. The lobule
      is reduced to four arches. Five points on the skull provide foundations for these
      arches, which react interdependently to extrinsic forces and positional change.
      When certain changes are imposed on the model, predictable alterations in the
      configuration of the model imitate the observed deformities in the spectrum of
      the cleft lip nasal deformity, unilateral and bilateral, mild through severe. The
      model is described with illustrations, anatomic dissection, physical models, and
      selected clinical cases. A better understanding of the mechanisms of the cleft
      nasal deformities can be obtained through analysis of the model.

PMID- 9583473
TI  - Does preexisting posterior pharyngeal wall motion drive the dynamism of sphincter
      pharyngoplasty?
AB  - Lateral speech videofluoroscopic evaluations were videotaped preoperatively and
      postoperatively for 20 patients who underwent sphincter pharyngoplasty.
      Randomized videotapes were constructed and subsequently evaluated by
      speech/language pathologists experienced in assessing patients with
      velopharyngeal dysfunction. Rating forms assessing various motion parameters of
      the posterior pharyngeal wall were completed and analyzed statistically. Results
      showed that the posterior pharyngeal wall configuration postoperatively was less
      likely to be rated as smooth relative to the preoperative configuration (p =
      0.019). No other statistically significant data were obtained, although there was
      a trend for posterior pharyngeal wall movement rated as discrete preoperatively
      to be described as generalized postoperatively. We conclude that when comparing
      preoperative and postoperative parameters, sphincter pharyngoplasty does not
      significantly affect posterior pharyngeal wall motion. Posterior pharyngeal wall
      configuration is less likely to be categorized as smooth after sphincter
      pharyngoplasty relative to the preoperative condition. Although sphincter
      pharyngoplasty has been shown to improve velopharyngeal function, there is little
      evidence from this study to suggest that preexisting posterior pharyngeal wall
      motion causes sphincteric movement.

PMID- 9583475
TI  - Quantitation of patterns of facial movement in patients with ocular to oral
      synkinesis.
AB  - As patients with facial paralysis regain facial nerve function, they must endure
      and adapt to complications associated with recovery, such as synkinesis.
      Synkinesis is the presence of unintentional movement in one area of the face when
      intentionally performing movement in another area of the face. We used the
      Maximal Static Response Assay of facial motion to better define the differences
      between eye closure-associated perioral motion in normal individuals, motion of
      the affected side in patients with synkinesis, and motion of the unaffected side
      in patients with synkinesis, thereby characterizing the syndrome of ocular to
      oral synkinesis. The study population consisted of 78 patients with clinically
      defined ocular to oral synkinesis of the left or right hemiface and 27
      individuals without facial impairment (control subjects). We used the Maximal
      Static Response Assay to quantify facial motion on the affected and unaffected
      sides during the motions of eye closure and smile in both groups. Patients with
      ocular to oral synkinesis had decreased supraorbital and infraorbital motion of
      the orbicularis oculi during eye closure on both the affected and unaffected
      sides relative to control subjects. They also had increased modiolar motion
      during eye closure on both sides relative to control subjects. On the affected
      side, the modiolus tended to move laterally; on the unaffected side, the modiolus
      tended to move medially (i.e., toward the side affected by the synkinesis).
      Modiolar motion present during eye closure in patients with ocular to oral
      synkinesis was not statistically different from modiolar motion present during
      smile on the affected side (eye closure, 0.39 cm +/- 0.25; smile, 0.47 cm +/-
      0.30, p > 0.05). Using the Maximal Static Response Assay, we have quantitatively
      defined synkinesis of the affected hemiface and have shown that movement of the
      unaffected hemiface is influenced by the synkinetic movements of the affected
      hemiface. These data may provide the basis for a rational system of facial
      neuromuscular rehabilitation in this patient group.

PMID- 9583474
TI  - One-stage reconstruction of eye socket and eyelids in orbital exenteration
      patients.
AB  - Reconstruction of the exenterated orbit is a difficult problem with several
      advantages and disadvantages. Satisfactory reconstructive results for both the
      physician and the patient may need multistage operations that are time consuming
      and disfiguring. A simple and effective one-stage technique that combines two
      regional flaps is described for reconstruction of deformities of orbital
      exenteration. A temporalis muscle flap is transposed for orbital filling, and a
      prefabricated frontal island flap based on superficial temporal vessels is used
      for eye socket and eyelid reconstruction. For patients who oppose living with
      exenteration deformity and request quicker reconstruction, this new and simple
      technique may be used successfully.

PMID- 9583476
TI  - Omentum flap versus pectoralis major flap in the treatment of mediastinitis.
AB  - The outcome of mediastinal reconstruction during the past 10 years at the
      "Instituto Nacional de Cardiologia Ignacio Chavez" (INCIC), Mexico City was
      compared. A total of 7136 patients were submitted to open heart surgery. Eighty
      two patients (1.15 percent) developed mediastinitis, and 33 patients (0.46
      percent) developed sternal osteomyelitis. Only patients who developed
      mediastinitis with sternal osteomyelitis were included in the study.
      Reconstruction was performed either with a major omentum flap (12 patients) or a
      pectoralis major flap (21 patients). The sepsis-related mortality rate was higher
      in the pectoralis group (28.6 percent) than in the omentum group (0 percent) (p <
      0.05). All of the postoperative deaths of the pectoralis group were caused by
      septic shock; in the omentum group, there were no such deaths. It is concluded
      that mediastinal reconstruction using the omentum flap in patients with
      mediastinitis secondary to open heart surgery is associated with fewer septic
      complications than using the pectoralis major flap.

PMID- 9583477
TI  - Nerve and vessel supplying ligamentous suspension of the mammary gland.
AB  - Anatomical findings from 28 breast specimens of female corpses have shown a thin
      horizontal fibrous septum, originating from the pectoral fascia along the level
      of the fifth rib, heading toward the nipple. This fibrous septum lies in between
      a cranial and a caudal vascular network, and being mesentery-like, it is
      responsible for the supply of the nipple areola complex. The cranial vascular
      sheet is supplied by the thoracoacromial artery and a branch of the lateral
      thoracic artery, whereas the caudal sheet is supplied by perforating branches
      from anastomoses of intercostal arteries. The fibrous septum is also a guiding
      structure for the main supplying nerve of the nipple. At its borders the septum
      curves upward into a vertical medial and lateral ligament, which attach the
      breast to the sternum and the lateral edge of pectoralis minor. These ligaments
      also contain a regular nerve and vascular supply. In their total, the fibrous
      septum and its ligaments form a sling of dense connective tissue that acts as a
      brassiere-like suspensory system. These two structures, the fibrous sling and the
      vascular and nervous membranes attached to it, are consistent anatomical
      findings, which have not been described before. Their knowledge could be of value
      and relevance in clinical application.

PMID- 9583478
TI  - Nipple-sparing total mastectomy of large breasts: the role of tissue expansion.
AB  - Nipple-sparing total mastectomy remains an alternative for management of patients
      with high risk breast disease or patients with various types of symptomatic
      breast problems. In a patient with large breasts, however, achieving good
      cosmesis while still performing a thorough mastectomy remains a challenge. This
      report includes 10 patients who underwent unilateral nipple-sparing total
      mastectomy and 10 patients who underwent bilateral nipple-sparing total
      mastectomy. Tissue expansion was used as the reconstructive technique in this
      consecutive series done from 1985 through 1988. All expanders were placed in the
      submuscular position, and hyperbaric oxygen was used when intraoperative
      fluorescein administration identified marginally perfused areas. The average
      volume of breast tissue removed was 800 gm. The average permanent implant size
      was 767 cc. Complications included partial skin or nipple loss, infection, and
      problems related to the implants themselves. The complication rate, however, was
      not excessive, and results have been good as measured by cosmetic results,
      capsule grade, and lack of development of cancer in operated breasts. This
      reconstructive technique is recommended as an alternative in those patients
      undergoing nipple-sparing total mastectomy.

PMID- 9583479
TI  - TRAM flap perforator ligation and the delay phenomenon: development of an
      endoscopic/laparoscopic delay procedure.
AB  - Despite its versatility in breast reconstruction, the TRAM flap is at times
      subject to ischemic compromise, especially in certain high risk populations. A
      preoperative delay procedure can decrease the likelihood of TRAM flap failure or
      fat necrosis, but the required extent of this delay procedure is not clearly
      defined. In an attempt to augment flap vascularity while reducing surgical
      dissection and morbidity, six distinct delay procedures and a nondelayed control
      were compared in a rat TRAM flap model (n = 8 for all groups). An important
      feature that was incorporated into several groups was the ligation of the
      contralateral rectus perforators through minimal skin incisions (endoscopic
      analogy, groups 4 to 7). The most effective delay procedure was the combination
      of contralateral rectus perforator ligation and ipsilateral dominant pedicle
      ligation (group 7), which was achieved with two minimal skin incisions and no
      significant flap undermining. This procedure reduced the flap necrosis from 63.2
      +/- 5.8 percent (control) to 13.5 +/- 3.3 percent (p < 0.001). After completion
      of the animal studies, clinical application of a "minimally invasive" TRAM flap
      delay procedure was then undertaken in eight high risk patients with only modest
      ischemic compromise. Although the clinical experience is too early to draw
      definite conclusions, we feel that "endoscopic delay" has potential as a modality
      that will increase flap vascularity but minimize the morbidity of the preliminary
      procedure.

PMID- 9583480
TI  - Abdominoplastic secondary full-thickness skin graft vaginoplasty for male-to
      female transsexuals.
AB  - When inversion of combined penile and scrotal skin flaps for vaginoplasty in male
      to-female transsexuals has become impossible or has not led to functional
      results, alternative vaginoplasty techniques should be considered.
      Colocolpopoiesis involves major surgery and often leads to disappointing long
      term results. An Abbe-McIndoe vaginoplasty applying split-thickness skin grafts
      often does not provide favorable results in the scarred area encountered after
      complications of skin flap inversion surgery. Because thicker skin grafts show
      less tendency to shrink, the use of a full-thickness skin graft has been
      advocated for vaginoplasty in females. In this paper, we present our technique of
      successful secondary vaginoplasty applying full-thickness skin grafts in six male
      to-female transsexuals. In patients with sufficient groin and abdominal skin to
      spare, a miniabdominoplasty allows for acceptable donor site scarring combined
      with correction of the abdominal skin surplus. In flat-tummied patients, the
      conventional abdominoplasty will allow for sufficient skin to be harvested to
      ensure successful secondary vaginoplasty. Abdominoplastic vaginoplasty has been
      proven to provide a good alternative whenever a laparotomy is not favored or is
      contraindicated in secondary cases.

PMID- 9583481
TI  - Use of laser Doppler flowmetry for estimation of the depth of burns.
AB  - The trend for treatment of deep second degree burns and third degree burns is
      toward early excision and skin grafting. The ability to predict burn depth
      accurately as early as possible is important for early excision and skin
      grafting. This study, prospectively evaluated the ability of laser Doppler flow
      measurements, obtained within 72 hours after burn injury, to predict the depth of
      burn wounds. A Periflux system 4001 laser Doppler flowmeter was used to measure
      the cutaneous microflow circulation of 100 selected points of burn wounds on 44
      inpatients and of 1680 selected points on 120 volunteers from March of 1993 to
      February of 1994. The mean value of superficial second degree burns checked by
      laser Doppler was 194.6 perfusion units (PU). The value of deep second degree
      burns was 59.7 PU, and the value of third degree burns was 5.1 PU. The mean
      normal cutaneous blood flow of 120 volunteers (control group) was between 4 and 9
      PU, except on the head, neck, hand, and foot. Blood flow of more than 100 PU
      correctly predicted (90.2 percent of cases) a superficial second degree burn.
      Blood flow between 100 and 10 PU correctly predicted (96.2 percent of cases) a
      deep second degree dermal burn. That of less than 10 PU correctly predicted (100
      percent of cases) a third degree burn. There was also a significant correlation
      between initial flow measurements and the depth of burn wounds. We conclude that
      laser Doppler flow measurements performed early after burn injury are useful in
      predicting the depth of burn wounds. Laser Doppler flowmetry has the advantage of
      being easy to use and noninvasive and of providing immediate results for early
      determination of burn depth. Laser Doppler flowmetry is useful in selecting
      patients for early excision and grafting of burn wounds.

PMID- 9583482
TI  - The inflammatory reaction in elective flap surgery.
AB  - The inflammatory response in three different flap procedures was investigated by
      measuring the preoperative and postoperative levels of C-reactive protein,
      leukocyte count, and body temperature. Patients scheduled for delayed breast
      reconstruction were operated on with the lateral thoracodorsal flap, the
      latissimus dorsi flap, or the pedicled TRAM flap. All patients received 2 gm of
      intravenous cloxacillin for antibiotic prophylaxis and 1 gm of paracetamol four
      times a day as basic treatment for postoperative pain. Within each treatment
      group, significant postoperative changes in C-reactive protein levels, leukocyte
      count, and body temperature were noted when compared with preoperative values.
      The highest C-reactive protein level (130 mg/ml) was found in the TRAM group on
      the third postoperative day. The kinetic pattern of C-reactive protein was
      similar for the latissimus dorsi flap and lateral thoracodorsal flap procedures,
      but the maximum C-reactive protein levels were significantly lower, 74 and 44
      mg/ml respectively. Small (0.5 to 0.9 degrees C) but significant differences in
      body temperature were also noted on the second and third postoperative day. The
      TRAM flap group had the highest, the latissimus dorsi flap group intermediate,
      and the lateral thoracodorsal flap group the lowest value. The postoperative C
      reactive protein levels seem to reflect the extent of the surgical trauma.

PMID- 9583483
TI  - The island posterior calf fasciocutaneous flap: an alternative to the
      gastrocnemius muscle for cover of knee and tibial defects.
AB  - The gastrocnemius muscle remains the workhorse for providing soft tissue over the
      knee and upper tibia. Nevertheless, we have found the island posterior calf
      fasciocutaneous flap to be a valuable alternative. We describe 10 cases in which
      an island posterior calf fasciocutaneous flap was used to cover defects over the
      knee and tibia. Three cases were after knee arthroplasty wound dehiscence, three
      cases were of traumatic soft-tissue loss, three cases involved replacement of
      unstable skin, and one case required closing a synovial fistula. This series is
      compared with 10 contemporaneous consecutive cases of soft-tissue loss around the
      knee that were reconstructed with a gastrocnemius muscle flap. Nine posterior
      calf fasciocutaneous flaps survived completely, and one flap had to be replaced
      because of poor flow. Although this flap is technically more demanding, we have
      found that it offers some advantages over the gastrocnemius. These include a
      greater flexibility of size and shape, a longer arc of rotation to reach
      suprapatellar defects, the provision of sensate skin with protective though crude
      sensation, less bulk, and the avoidance of a twitch. The flap is also easy to re
      elevate from the recipient site for subsequent orthopedic work.

PMID- 9583484
TI  - The neurocutaneous flap based on the dorsal branches of the ulnar artery and
      nerve: a new flap for extensive reconstruction of the hand.
AB  - Soft-tissue repair in the hand often requires skin flaps due to exposure of bone,
      tendons, nerves, and arteries. However, alternatives for flap surgery are very
      limited, especially in dealing with palmar hand reconstruction. In the present
      report, the dorsal branch of the ulnar nerve and its accompanying artery were
      studied anatomically, and a neurocutaneous flap distally based on these
      structures was developed. The flap was raised on the medial aspect of the hand
      and distal half of the forearm, and its rotation point was located dorsally near
      the metacarpalphalangeal joints. The clinical use of this flap for the repair of
      skin defects in the hand is reported. All the clinical flaps survived completely,
      including a 3.5 x 13-cm large flap. Donor site morbidity was minimal. This flap
      represents a new alternative in hand reconstruction.

PMID- 9583485
TI  - Replantation of degloved skin of the hand.
AB  - The treatment of a degloving injury is one of the most difficult problems in hand
      surgery. Various reconstructive procedures have been adopted in the past years,
      all with poor results. Between 1988 and 1995, nine patients with degloving
      injuries of the hand and fingers were treated by microsurgical replantation. The
      injury involved the thumb in three patients, the ring finger in three patients,
      the little finger in one patient, and multiple fingers in two patients.
      Successful complete revascularization was obtained in seven patients. In one case
      a superficial necrosis of the replanted thumb skin occurred with good
      preservation of the subcutaneous layer. In one patient with a degloving injury
      involving multiple fingers, revascularization was achieved only in the middle
      finger, and the first ray was secondarily resurfaced by a free flap from the
      foot. In our experience revascularization of the degloved skin does represent the
      best solution and must be managed as an emergency procedure. Coverage obtained in
      this way offers the best cosmetic result and allows early mobilization with good
      recovery of joint movement. Reestablishing sensibility is more difficult. It is
      not always possible to suture the nerves damaged by the trauma, and even when a
      careful primary nerve anastomosis is performed, the results often are
      unsatisfactory, probably because of the avulsive mechanism of nerve injury.

PMID- 9583486
TI  - Effect of cultured endothelial cells on angiogenesis in vivo.
AB  - The purpose of this study is to evaluate the effect of cultured endothelial cells
      on angiogenesis in vivo. Endothelial cells obtained from thoracic aorta of male
      Wistar rats were cultured in thermoresponsive dishes, which are tissue culture
      polystyrene dishes bound with thermoresponsive poly (N-isopropylacrylamide).
      Using the thermoresponsive dishes, a confluent layer of endothelial cells can be
      detached as an intact sheet by low temperature treatment. The obtained sheets of
      cultured endothelial cells were grafted to 3 x 3 cm full-thickness skin defects
      that had been made on the backs of rats in combination with either free skin
      grafts or artificial dermis grafts. Histologic examinations were performed. The
      findings showed that, with each of the grafting procedures, the number of vessels
      in a unit area (1.0 x 10(-4) mm2) was significantly larger in the group with
      transplantation of cultured endothelial cells. This result suggests that the
      cultured vascular endothelial cells exert an angiogenic effect at the graft site.

PMID- 9583487
TI  - Biomechanical and histologic alteration of facial recipient bone after
      reconstruction with autogenous bone grafts and alloplastic implants: a 1-year
      study.
AB  - Potential alteration of the underlying recipient bone resulting from a graft or
      implant has significant clinical relevance. The present study was designed to
      evaluate the biomechanical and histologic alteration of facial recipient bone
      with autogenous bone graft and alloplastic implants over a 1-year period. The
      bilateral arches of 15 rabbits were randomized between four groups: (1) control
      (n = 6), subperiosteal exposure of the zygomatic arch was made; (2) onlay (n =
      12), bone graft was placed as an onlay to the zygomatic arch; (3) inlay (n = 6),
      bone graft was placed as an inlay within the zygomatic arch; (4) implant (n = 6),
      a stainless steel plate was placed as an onlay to the zygomatic arch. Animals
      were killed 1 year after grafting. In the onlay groups, all steel implants and
      half of the onlay bone grafts (n = 6) were separated from the zygomatic arch; the
      remaining onlay bone grafts (n = 6) were left on the zygomatic arch. Three-point
      breaking strength was measured through the center of the graft/implant site on
      the zygomatic arch, followed by histologic evaluation and histometric assessment
      of residual bone density. The findings demonstrated no difference in the breaking
      strength per unit bone area between the control zygomatic arch group and the
      onlay group in which the bone graft was left in place. Breaking strength of the
      zygomatic arch in the former two groups was significantly greater than that in
      either group in which the onlay bone graft or implant had been removed, and was
      also greater than the breaking strength in that group in which inlay bone had
      been placed (p < 0.05). Histologic assessment showed full-thickness conversion in
      architecture of the zygomatic arch from compact to woven bone beneath onlays of
      either autogenous bone graft or steel implant; histometric assessment
      demonstrated an accompanying decrease in bone density in the latter groups
      relative to the control zygoma (p < 0.05). We conclude that onlay autogenous bone
      graft and alloplastic implants to the facial skeleton induce transformation of
      both graft and recipient bone from compact to woven architecture, accompanied by
      a reduction in bone density. The biomechanical strength of recipient facial bone
      is significantly weakened if an onlay bone graft or implant is removed. Weakening
      occurs per unit area of remaining bone, and is therefore independent of any
      thinning that may occur within the recipient bone because of graft/implant
      placement. These findings may impact upon decisions to augment stress-bearing
      regions of the facial skeleton with bone graft or implants, particularly if the
      graft/implant may eventually require removal.

PMID- 9583489
TI  - Tissue engineered neocartilage using plasma derived polymer substrates and
      chondrocytes.
AB  - This study demonstrates that fibrin monomers can be polymerized into moldable
      gels and used for the encapsulation of isolated chondrocytes. This biologically
      derived scaffold will maintain three-dimensional spatial support, allowing new
      tissue development in a subcutaneous space. Chondrocytes isolated from the
      glenohumeral and humeroradioulnar joints of a calf were combined with
      cyroprecipitate and polymerized with bovine thrombin to create a fibrin glue gel
      with a final cell density of 12.5 x 10(6) cells/ml. The polymer-chondrocyte
      constructs were implanted subcutaneously in 12 nude mice and incubated for 6 and
      12 weeks in vivo. Histologic and biochemical analysis including deoxyribonucleic
      acid (DNA) and glycosaminoglycan quantitation confirmed the presence of actively
      proliferating chondrocytes with production of a well-formed cartilaginous matrix
      in the transplanted samples. Control specimens from 12 implantation sites
      consisting of chondrocytes alone or fibrin glue substrates did not demonstrate
      any gross or histologic evidence of neocartilage formation. Moldable autogenous
      fibrin glue polymer systems have a potential to serve as alternatives to current
      proprietary polymer systems used for tissue engineering cartilage as well as
      autogenous grafts and alloplastic materials used for facial skeletal and soft
      tissue augmentation.

PMID- 9583488
TI  - Effect of keratinocyte seeding of collagen-glycosaminoglycan membranes on the
      regeneration of skin in a porcine model.
AB  - A collagen-glycosaminoglycan matrix, impregnated with autologous keratinocytes,
      was applied as island grafts onto full-thickness porcine wounds to determine
      whether complete epidermal coverage could be achieved in a single grafting
      procedure. Twenty-four grafts with seeding densities ranging from 0 to 3,000,000
      cells/cm2 were used to determine the kinetics of epidermal coverage. The time
      sequence of epidermal formation was then studied between days 14 and 28 using
      four additional grafts, each seeded with a density of 500,000 cells/cm2.
      Autologous keratinocytes proliferated as the collagen-glycosaminoglycan matrix
      was vascularized to form a confluent epidermis by 2 weeks in matrices seeded with
      at least 100,000 cells/cm2. The epidermal thickness and the number of
      keratinocyte cysts observed in the neodermis at 2 weeks increased linearly with
      the logarithm of the seeding density. Sequential analysis of neoepidermis showed
      the nascent epidermis to be hyperplastic, parakeratotic, and focally lacking in
      granular layer differentiation at 2 weeks. After 2 weeks, it underwent normal
      maturation and differentiation. Irrespective of seeding density at 2 weeks the
      collagen-glycosaminoglycan matrix was well vascularized, contained a dense
      cellular infiltrate, and was almost completely degraded. These studies
      demonstrate that seeded keratinocytes proliferate and differentiate to form a
      confluent epidermis by 2 weeks in matrices seeded with at least 100,000
      cells/cm2.

PMID- 9583490
TI  - Monoclonal antibody to intercellular adhesion molecule 1 protects skin flaps
      against ischemia-reperfusion injury: an experimental study in rats.
AB  - The purpose of this study was to evaluate the blockage of polymorphonuclear
      neutrophil endothelial adhesion by using a monoclonal antibody to the
      intercellular adhesion molecule 1 (ICAM-1) ligand to prevent ischemia-reperfusion
      injury in rat skin flaps. A skin and subcutaneous tissue flap (3.0 cm x 4.5 cm)
      supplied by the superficial epigastric artery and vein including the femoral
      vessels was isolated unilaterally in 45 male Sprague-Dawley rats and clamped for
      9 hours (groups II and III) or 12 hours (groups IV and V) of ischemia. Five
      animals in group I were sham-operated only with 5 minutes of ischemia. Animals in
      groups II (n = 10) and IV (n = 10) received 0.05 mg of monoclonal antibody to
      ICAM-1 (0.20 mg/kg) in 0.5 ml of 0.9% normal saline intravenously 15 minutes
      before reperfusion; those in groups III (n = 10) and V (n = 10) received 0.5 ml
      of normal saline. The flaps were assessed histologically, by measuring viable and
      nonviable areas, and by diffuse reflectance spectroscopy to determine the ratio
      of oxyhemoglobin to deoxyhemoglobin. Flap measurements revealed that the average
      area of flap survival was 90.6 +/- 12.8 percent in group II and 18.3 +/- 19.6
      percent in the control group (III) (p < 0.002). In the animals subjected to 12
      hours of ischemia, those treated with monoclonal antibody to ICAM-1 (group IV)
      were 57.1 +/- 23.1 percent viable, which was significantly greater than the
      control animals (group V), in which only 0.3 +/- 1.0 percent of the flap was
      viable. Analysis of the diffuse reflectance spectra showed a hyperemic response
      during the first 10 minutes after reperfusion in animals treated with monoclonal
      antibody to ICAM-1. In group III, however, the spectra demonstrated a decreased
      amount of oxyhemoglobin, indicating decreased reperfusion of the flap after
      ischemia when compared with group II. Histopathologically, few inflammatory
      changes could be observed in groups I, II, and the viable areas of group IV.
      Marked damage was observed in groups III and V. We concluded that treating
      ischemic skin flaps with monoclonal antibody to ICAM-1 was effective for
      alleviating reperfusion injury after 9 or 12 hours of warm ischemia. The reactive
      hyperemic response determined by diffuse reflectance spectroscopy in groups II
      and IV correlated with areas of flap survival. Antibodies to particular adhesion
      molecules, such as ICAM-1, have potential clinical utility in that they could be
      administered, individually or together, to patients immediately before
      reestablishing perfusion after free-tissue transfer or replantation to block the
      adverse effects attributed to reperfusion injury.

PMID- 9583491
TI  - Critical role of phosphagens in the energy cascade of cutaneous ischemia and
      protective action of phosphocreatine analogues in skin flap survival.
AB  - A general understanding of the pivotal role of phosphocreatine (PCr) as the
      principal determinant of skin flap survival is now emerging. Definitive metabolic
      investigations using phosphorus (31P) and proton (1H) magnetic resonance
      spectroscopy (MRS) have established that the inability to replenish metabolically
      exhausted PCr reserves predictably correlates with skin flap necrosis.
      Furthermore, postoperative parenteral administration of PCr has been shown to
      augment effectively skin flap survival. We hypothesized that creatine kinase, the
      enzyme controlling the utilization of the high-energy phosphate component of PCr,
      is a critical determinant of the tolerance of a skin flap to ischemic insult. In
      other words, if the rate of utilization of PCr is too rapid, PCr stores will
      rapidly deplete, and the flap will not be able to withstand a period of ischemia.
      Alternatively, if the rate of dephosphorylation of PCr is reduced, survival of
      skin flaps during periods of ischemia could be extended. To test this hypothesis,
      we investigated the metabolic distribution and fate of cyclocreatine (cCr), a
      competent creatine analogue with a lower affinity for the creatine kinase enzyme.
      When administered as 1.5 percent (w/w) of the normal diet of laboratory rats, cCr
      accumulates in skin as the competent phosphagen, phosphocyclocreatine (PcCr).
      Cutaneous flaps elevated in these animals, and studied by 31P and 1H MRS,
      demonstrate that once depletion of PCr has occurred, PcCr continues to sustain
      ATP levels. This results in significant enhancement of skin flap survival (p <
      0.005). These observations confirm the importance of the creatine kinase enzyme
      in cutaneous flap ischemia and suggest new approaches to augment skin flap
      survival.

PMID- 9583492
TI  - Successful replantation of an amputated tongue.

PMID- 9583493
TI  - Emergency rotationplasty of ankle to knee.

PMID- 9583494
TI  - Ipsilateral second metatarsal island osteocutaneous flap for lower extremity
      reconstruction.

PMID- 9583495
TI  - Reconstruction of four metatarsal bone and soft-tissue defects using a serratus
      anterior muscle rib osteomyocutaneous free flap.

PMID- 9583496
TI  - Correction of the unilateral question mark ear.

PMID- 9583497
TI  - Functional and aesthetic reconstruction using a nasolabial orbicularis oris
      myocutaneous flap for large defects of the upper lip.

PMID- 9583498
TI  - Croissant flap: an axial pattern flap of neck skin below the mandible with
      posterior random extension.

PMID- 9583499
TI  - Mini Z in Z to relieve the tension on the transverse closure after Z-plasty
      transposition.

PMID- 9583500
TI  - Microport approach in subcutaneous endoscopic surgery.

PMID- 9583501
TI  - Body image dissatisfaction and body dysmorphic disorder in 100 cosmetic surgery
      patients.
AB  - This study was the first empirical investigation of body image dissatisfaction
      and body dysmorphic disorder in cosmetic surgery patients. Of 132 women, 100
      women (response rate, 76 percent) completed two body image measures prior to
      surgery, the Multidimensional Body-Self Relations Questionnaire and the Body
      Dysmorphic Disorder Examination Self-Report. Cosmetic surgery patients did not
      demonstrate greater dissatisfaction with their overall appearance compared with
      the reported normal values of the measures. However, when asked about the
      specific bodily feature they were considering for cosmetic surgery, they reported
      significantly greater dissatisfaction than a normative sample. In addition, 7
      percent of the sample met diagnostic criteria for body dysmorphic disorder, a
      potential psychiatric contraindication to cosmetic surgery. Implications of these
      findings are discussed with respect to the nature of body image dissatisfaction
      and the prevalence of body dysmorphic disorder in cosmetic surgery populations.

PMID- 9583502
TI  - The medial SMAS lift with aggressive temporal skin takeout.
AB  - The ability to correct prominent nasolabial folds has remained a consistent
      weakness in facial rejuvenation surgery. Cadaveric studies were performed to
      evaluate differential properties of the superficial musculoaponeurotic system
      (SMAS) unit. We have found that the medial portion of the SMAS unit has a much
      more scattered, irregular collagen architecture and exhibits greater
      distensibility. Based on the regional differences in the physical properties and
      architecture of the SMAS, a face lift procedure is described in which the medial
      portion of the SMAS is resuspended, combined with aggressive temporal skin
      takeout in a pants-over-vest fashion. The procedure has been performed by the
      senior author in 89 patients. It is often combined with the "central" suspension
      and has provided more predictable results in this surgeon's hands.

PMID- 9583504
TI  - An alar base flap to correct nostril and vestibular stenosis and alar base
      malposition in rhinoplasty.
AB  - Nostril and vestibular stenoses can be properly reconstructed by composite grafts
      from the alar lobule or ear. However, when alar base malposition accompanies the
      nostril stenosis, composite grafting will enlarge the nostril but not correct the
      alar base displacement. An alar base flap designed as a crescent adjacent to the
      alar base, elevated, and transposed on subcutaneous and musculocutaneous
      perforators corrects the nostril stenosis and repositions the alar base
      simultaneously. Anterior, active rhinomanometry demonstrates a substantial
      increase in mean nasal airflow from this reconstructive maneuver alone. The
      author has used the flap successfully in 29 secondary rhinoplasty patients;
      survival has been uniformly complete even when the donor tissue has been scarred
      or burned. All rhinoplasties were performed endonasally, however; the survival of
      this flap performed simultaneously with open rhinoplasty has not been
      established.

PMID- 9583503
TI  - Septo-orbitoperiostoplasty for the treatment of palpebral bags: a 10-year
      experience.
AB  - The orbital region is sensitive to the undesirable effects of any surgical
      intervention, because of its anatomical location and the importance of the
      eyelids in facial sign language. The procedures performed for correction of baggy
      eyelids may have remarkable undesired results. In recent years, we have made a
      special effort to analyze the causes, to minimize these undesirable effects, and
      to be able to offer patients more natural and safer results. We have designed a
      new technique called septo-orbitoperiostoplasty for the treatment of baggy
      eyelids, based on preservation of orbital fat and correction of the supportive
      layer. This technique consists of placing the orbital fat back into the orbital
      cavity and its retention by suturing the lax septum to the periosteum of the
      orbital rim. Neither an incision on the orbital septum nor an excision of the
      orbital fat is performed. It can be performed for both upper and lower eyelids.
      This paper describes the surgical procedure and shows the results obtained from
      74 patients who had been treated with this technique over a 10-year period. All
      patients were followed up for an average of 5 years.

PMID- 9583505
TI  - A 6-year experience with the use of expanded polytetrafluoroethylene in
      rhinoplasty.
AB  - To date, there are few published large series within the literature on the use of
      expanded polytetrafluoroethylene (Gore-Tex) in rhinoplasty. This retrospective
      study, based on chart and photographic reviews, serves to contribute a 6-year
      experience (mean patient follow-up period, 17.5 months) with the alloplast in
      nasal surgery amassed by one surgeon. The same technique was used in all the 189
      patients reviewed, who received 211 procedures. The 189 patients, 44 male and 145
      female and from 15 to 70 years of age, were reviewed 3 months to 6 years after
      Gore-Tex implantation rhinoplasties. The results were assessed according to the
      follow-up notes in the chart reflecting patients' and surgeon's comments and full
      preoperative and postoperative photographic documentation. Patient satisfaction
      was expressed with respect to aesthetic and functional outcome in all cases.
      Patient impressions were verified by critical assessment during follow-up
      examination. The implants showed excellent stability and tissue tolerance.
      Complications requiring removal occurred in 2.7 percent of implants placed. The
      authors are of the opinion that, in rhinoplasty, with the exception of the nasal
      tip, columella, or problems in which corrections would require rigidity of the
      grafted or implanted material, the Gore-Tex alloplast is an excellent alternative
      to autografts. Nasal tip or columellar sites do not render adequate soft-tissue
      cover, allowing the implant to rest close to the surgical incision. Because this
      creates additional risk of implant extrusion, such locations were avoided in the
      series of patients presented.

PMID- 9583506
TI  - Rectus muscle diastasis in males: primary indication for endoscopically assisted
      abdominoplasty.
AB  - Endoscopic techniques through umbilical and mons pubis ports have provided a
      method to plicate rectus muscle diastasis without skin resection. Limited or no
      skin excision is performed. Major series have included only women. The criteria
      for patient selection for endoscopic abdominoplasty include a protuberant abdomen
      caused by rectus muscle diastasis with minimal actual or potential skin laxity.
      There should not be significant intra-abdominal obesity. Extra-abdominal familial
      fat deposits may be part of the abdominal aesthetic deformity. In most women,
      rectus muscle diastasis because of pregnancy, obesity, or aging is associated
      with actual or potential skin laxity of the abdomen and lateral trunk. Endoscopic
      abdominoplasty in these women would produce mediocre early results and poor aging
      potential for the future. There are a limited number of women who are reasonable
      candidates for the endoscopic approach. In contrast, rectus muscle diastasis
      without skin laxity is a common finding in men older than 30 to 40 years of age.
      There may be a history of weight fluctuations, weightlifting, or full-excursion
      sit-up exercises, which may lead to progressive separation of the rectus muscles
      over time. Other etiologic factors include chronic or intermittent abdominal
      distension, advancing age, or familial weakness of the abdominal musculofascial
      tissues. Endoscopically assisted abdominoplasty was performed in four male
      patients with good to excellent results at 4 to 18 months. Minor complications
      occurred in half the patients but were successfully treated without re-operation.
      Men with prominent abdominal contours who are diet- and exercise-resistant should
      be examined both for familial fat deposits and for significant rectus muscle
      diastasis. Contouring of the male abdomen may be the primary indication for
      endoscopically assisted abdominoplasty.

PMID- 9583507
TI  - Areolar reduction with inner doughnut incision.

PMID- 9583509
TI  - The credentials committee--friend or foe?

PMID- 9583508
TI  - Use of the Mitek fixation device in endoscopic browlifting.

PMID- 9583511
TI  - A fetal surgery primer for plastic surgeons.

PMID- 9583512
TI  - New synthetic orbital implant for orbital floor repair.

PMID- 9583513
TI  - Closing defects in the mid-lateral portion of the upper lip.

PMID- 9583514
TI  - Browpexy as an adjunct to blepharoplasty.

PMID- 9583515
TI  - Postoperative compressive penile dressing using fibrin seal (Tisseel) and tulle
      gauze for hypospadias repair.

PMID- 9583516
TI  - Hyperbaric oxygen treatment for wounds.

PMID- 9583517
TI  - "Re-applying".

PMID- 9583518
TI  - Treatment of cutaneous lesions of the back.

PMID- 9583519
TI  - Reconstructing the external auditory canal.

PMID- 9583520
TI  - Caveat against using ultrasonically assisted lipectomy in aesthetic breast
      surgery.

PMID- 9583521
TI  - The bi-lobed flap design on expanded skin of the face and neck region.

PMID- 9583522
TI  - Educating a plastic surgeon.

PMID- 9583524
TI  - Hairline incisions.

PMID- 9583523
TI  - Reverse-flow flaps in rats.

PMID- 9583525
TI  - The Scarpa fascia flap.

PMID- 9583526
TI  - Fibrin glue to prevent seroma formation.

PMID- 9583527
TI  - Use of fibrin sealant to prevent seromas in rats.

PMID- 9583528
TI  - Surgical delay with a TRAM flap.

PMID- 9583529
TI  - Producing tissue-engineered cartilage in the shape of a human ear.

PMID- 9583530
TI  - A new observation in ulnar nerve motor palsy: compensation of adduction by finger
      flexion.

PMID- 9583531
TI  - Mesh-over dressing: tie-over dressing without tie-over.

PMID- 9583532
TI  - Vermilion response to trauma.

PMID- 9583533
TI  - "The overlap flap".

PMID- 9583534
TI  - The purse-string suture.

PMID- 9583535
TI  - Closing skin defects with purse-string suture.

PMID- 9583537
TI  - A circumferential presurgical sterile preparation for extensive body liposuction.

PMID- 9583536
TI  - The tumescent technique.

PMID- 9583538
TI  - "Lipodermolift": a natural outcome of superficial liposuction.

PMID- 9583539
TI  - Difficult tubes and difficult airways.

PMID- 9583540
TI  - The interaction between applied PEEP and auto-PEEP during one-lung ventilation.
AB  - OBJECTIVE: To investigate the relationship between applied external positive end
      expiratory pressure (PEEP) and auto-PEEP and the resultant total PEEP experienced
      by the patient during one-lung ventilation (OLV). DESIGN: A prospective clinical
      study. SETTING: A university hospital. PARTICIPANTS: Ten adult patients
      undergoing elective thoracotomies. INTERVENTIONS: End-expiratory airway occlusion
      and measurement of plateau pressure during two-lung ventilation (TLV) and OLV
      with and without the application of 5 cm H2O of external PEEP via the anesthetic
      ventilator. The effect of variation of the inspiratory-expiratory ratio on total
      PEEP with and without applied external PEEP was also studied. MAIN RESULTS: The
      mean level (+/-SD) of auto-PEEP changing from two-lung to one-lung ventilation
      rose from 0.9 (+/-0.8) cm H2O to 6.0 (+/-3.0) cm H2O at an inspiratory-expiratory
      ratio of 1:2. The application of 5 cm H2O external PEEP did not increase the
      total PEEP (7.3+/-2.0 cm H2O) significantly. The total PEEP increased
      significantly when the duration of expiration was decreased, and decreased when
      expiratory time increased. The change in total PEEP caused by the application of
      external PEEP during OLV correlated inversely with the preexisting level of auto
      PEEP (r=-0.84). CONCLUSION: The change in end-expiratory pressure experienced by
      the ventilated lung during OLV when external PEEP is applied depends on the
      preexisting level of auto-PEER This may explain some of the inconsistencies in
      the clinical results of application of external PEEP during OLV. The total PEEP
      delivered to the patient should be measured whenever external PEEP is applied
      during OLV.

PMID- 9583542
TI  - Flow resistances of disposable double-lumen, single-lumen, and Univent tubes.
AB  - OBJECTIVE: To compare the airflow resistances of modern double-lumen, single
      lumen, and Univent (Fuji Systems Corp; Tokyo, Japan) tubes. DESIGN: A laboratory
      bench study. SETTING: A university hospital laboratory. MEASUREMENTS: Pressure
      differentials (Pd) were measured across study tubes at 10 L/min airflow (V)
      increments from 0 to 60 L/min in a tracheal model. Coefficients of resistance k1
      (linear) and k2 (nonlinear) were calculated for each tube by the method of least
      squares using the Rohrer equation Pd/V = k1 + k2V. Data were assessed by analysis
      of variance (ANOVA) for the effects of tube design, circumference, and
      manufacturer on k1 and k2. MAIN RESULTS: Calculated combined mean k1 and k2 were
      significantly lower for single-lumen tubes compared with double-lumen or Univent
      tubes. There were no significant differences for k1 values between double-lumen
      or Univent tubes. The values for k2 were significantly lower for double-lumen
      tubes compared with Univent tubes. The k2 values were significantly lower for
      Rusch (Duluth, GA) or Sheridan (Argyle, NY) double-lumen tubes compared with
      Mallinckrodt (St Louis, MO) double-lumen tubes. This difference was because of
      the Y-connectors of the Mallinckrodt tubes. CONCLUSIONS: Flow resistances of
      modern disposable double-lumen tubes are lower than commonly perceived. In most
      clinical situations, there will be no decrease in flow resistance when a Rusch or
      Sheridan double-lumen tube is replaced by a single-lumen tube.

PMID- 9583541
TI  - Respiratory mechanics and gas exchange during one-lung ventilation for thoracic
      surgery: the effects of end-inspiratory pause in stable COPD patients.
AB  - OBJECTIVE: To examine the effects of end-inspiratory pause (EIP) of different
      durations on pulmonary mechanics and gas exchange during one-lung ventilation
      (OLV) for thoracic surgery. DESIGN: A prospective clinical study. SETTING: A
      university hospital. PARTICIPANTS: Eleven patients undergoing elective pulmonary
      resection with pulmonary hyperinflation on their preoperative pulmonary function
      studies. INTERVENTIONS: Patients were anesthetized, paralyzed, and intubated with
      a double-lumen endotracheal tube. Their lungs were ventilated with a Siemens 900C
      ventilator (Siemens; Solna, Sweden), with constant inspiratory flow. Tidal
      volume, respiratory rate, and inspiratory time were kept constant during the
      study. MEASUREMENTS AND RESULTS: During one-lung ventilation in the lateral
      decubitus position, three levels of EIP (0%, 10%, and 30%) were applied to the
      dependent lung in random order. After 15 minutes on the given ventilatory
      pattern, end-inspiratory and end-expiratory occlusions of at least 5 seconds were
      performed to obtain respiratory mechanics data. Arterial blood gas samples were
      drawn to assess gas exchange. Altering the duration of end-inspiratory pause from
      0% to 30% resulted in a significant increase in intrinsic positive end-expiratory
      pressure (PEEPi) from 4.1 cm H2O to 7.0 cm H2O. Arterial oxygenation was
      significantly decreased from 109.7 to 80.5 mmHg and there was a significant
      negative correlation between the value of partial pressure of arterial oxygen
      (PaO2) and PEEPi by altering the duration of end-inspiratory pause. From the
      preoperative pulmonary function studies, the value of functional residual
      capacity (FRC) (% predicted) showed a significant negative correlation with the
      PaO2 changes. Partial pressure of arterial carbon dioxide (PaCO2) was not altered
      significantly by increasing the duration of end-inspiratory pause. CONCLUSION:
      During the period of OLV in the lateral position of patients with preexisting
      pulmonary hyperinflation, the magnitude of PEEPi increased and oxygenation
      decreased significantly, whereas the efficacy of ventilation was not changed by
      the addition of an end-inspiratory pause to the ventilatory pattern. Because
      arterial oxygenation is affected by the presence of pulmonary hyperinflation, the
      method of ventilation should take into account the magnitude of preoperative
      pulmonary hyperinflation.

PMID- 9583543
TI  - Airway compression in children due to congenital heart disease: value of flexible
      fiberoptic bronchoscopic assessment.
AB  - OBJECTIVE: To evaluate the frequency and severity of airway compression due to
      congenital heart disease in children and validate the use of the fiberoptic
      bronchoscope to assess them. DESIGN: A retrospective study. SETTING: A single
      institutional study in a university hospital. PARTICIPANTS: Seventy-two children
      with congenital heart disease. INTERVENTIONS: Airway endoscopy was performed in
      an awake child in cases of clinical and/or radiologic respiratory signs or in
      cases of preoperative assessment of a cardiac abnormality that is known to
      accompany airway compression. MEASUREMENTS AND MAIN RESULTS: Endoscopy was well
      tolerated; 71% of the children had endoscopic abnormalities and 50% had airway
      compression. The locations of these compressions are the same as those described
      in the literature in the cases of vascular rings and left-to-right shunts. The
      other endoscopic findings were laryngeal and bronchial abnormalities,
      tracheobronchial malacia, respiratory signs of gastroesophageal reflux, and
      positive bacteriologic sputum samples. CONCLUSION: Endoscopy in an awake patient
      is the only way to evaluate the functional component of a compression due to
      malacia; the resulting collapse of the airway can cause trapping of air and
      secretions. Furthermore, fiberoptic bronchoscopy offers a complete examination of
      the airways and can help detect airway abnormalities that are potential causes of
      complications. Fiberoptic bronchoscopy is a suitable and well-tolerated
      examination that is easy to perform at the bedside of the child. This technique
      optimizes the preoperative assessment of children with congenital heart disease.

PMID- 9583544
TI  - Anesthetic management of laser surgery for central airway obstruction: a 12-year
      case series.
AB  - The retrospective 12-year experience of anesthetizing patients with central
      airway obstructions for laser treatment with a CO2 and two types of Nd:YAG laser
      has been reviewed and evaluated. More than 300 patients have been treated, many
      on several occasions. The beneficial effects of treatment to the majority of
      patients have been significant. There has been a small associated mortality
      because the majority are in the high-risk categories of fitness for anesthesia,
      but no clinical evidence that it is directly attributable to the techniques of
      anesthesia or ventilation. Therefore, although laser technology has evolved into
      systems suitable to be applied with fiberoptic bronchoscopes and local and
      sedation anesthesia, the use of a rigid bronchoscope and the evolved techniques
      of anesthesia and ventilation remain appropriate to the clinical needs and offer
      advantages.

PMID- 9583545
TI  - Effects of inhaled nitric oxide on respiratory system mechanics, hemodynamics,
      and gas exchange after cardiac surgery.
AB  - OBJECTIVE: To evaluate the hemodynamic and respiratory effects of inhaled nitric
      oxide (NO) in postoperative cardiac patients. DESIGN: A prospective evaluation.
      SETTING: A university hospital intensive care unit. PARTICIPANTS: Fourteen adults
      with pulmonary hypertension, studied postoperatively. INTERVENTIONS: 60 minutes
      of NO inhalation (20 ppm). MEASUREMENTS AND MAIN RESULTS: Respiratory mechanics
      were analyzed by inflating the relaxed respiratory system with constant flow,
      followed by rapid airway occlusion at end-inflation, which was maintained until a
      plateau in tracheal pressure was obtained. Gas exchange and hemodynamics were
      evaluated by conventional means. The data were studied using the analysis of
      variance for repeated measures. Minimum airway resistance (Rmin) increased
      significantly from 8.87+/-3.24 cm H2O/L x s to 9.69 +/-3.22 cm H2O/L x s at the
      end of NO inhalation and remained elevated after NO was discontinued. A selective
      vasodilator effect on pulmonary vasculature was observed in the pulmonary
      systemic vascular resistance ratio, which decreased from 0.18+/-0.11 to 0.13+/
      0.08 at the end of inhalation and returned to baseline values after gas
      suspension. No significant alterations in oxygenation were observed. CONCLUSION:
      The effects of NO as a powerful and useful vasodilator agent were confirmed.
      However, it is important to be aware that the effects observed on respiratory
      mechanics may interfere with the final response of the respiratory system to NO.

PMID- 9583546
TI  - A comparative evaluation of intrapleural and thoracic epidural analgesia for
      postoperative pain relief after minimally invasive direct coronary artery bypass
      surgery.
AB  - OBJECTIVE: To compare the efficacy of thoracic epidural analgesia (TEA) and
      intrapleural analgesia (IPA) after minimally invasive direct coronary artery
      bypass (MIDCAB) surgery with regard to quality of analgesia and complications.
      DESIGN: A prospective, randomized study. SETTING: A specialty research hospital.
      PARTICIPANTS: Fifty consenting adults scheduled for MIDCAB surgery.
      INTERVENTIONS: All patients underwent elective MIDCAB surgery. Patients in the
      TEA group (n=25) had an epidural catheter inserted in the fourth to fifth
      thoracic interspace and those in the IPA group (n=25) had an intrapleural
      catheter inserted in the sixth to seventh intercostal space intraoperatively
      under vision. MEASUREMENTS AND MAIN RESULTS: Parameters evaluated after
      administration of bupivacaine (8 mL of 0.25% in the TEA group and 20 mL of 0.25%
      in the IPA group) on first demand included visual analog scale (VAS) pain scores,
      cardiovascular and respiratory (clinical, blood gases) function, wakefulness,
      supplemental analgesic requirement, and complications. Measurements were made at
      2-hour intervals for the next 12 hours. VAS scores were significantly lower at 2,
      6, 8, and 12 hours in the IPA group (TEA = 3.5, 4.5, 4.9, 4.6; IPA = 2.2, 3.6,
      3.5, 3.7). There were no significant differences in hemodynamic or respiratory
      parameters or postoperative requirement for supplemental analgesia. In the TEA
      group, three patients had catheter migration and four had severe backache.
      CONCLUSION: IPA is a safe and effective technique for postoperative analgesia
      after MIDCAB surgery and has a low complication rate compared with TEA. Careful
      positioning, chest tube clamping, and anchoring of the catheter are mandatory for
      IPA to be effective.

PMID- 9583547
TI  - Pleural bupivacaine placement for optimal postthoracotomy pulmonary function: a
      prospective, randomized study.
AB  - OBJECTIVE: To determine dependent chest tube losses of bupivacaine with
      paravertebral versus interpleural administration, thereby helping to explain the
      significant differences in pulmonary function that exist between these two
      techniques. DESIGN: A prospective, randomized study. SETTING: A single hospital.
      PARTICIPANTS: Twelve adult patients undergoing posterolateral thoracotomies.
      INTERVENTIONS: Paravertebral or interpleural administration of bupivacaine.
      MEASUREMENTS AND MAIN RESULTS: Analgesia, as assessed by visual analog pain
      scores and patient-controlled morphine requirements, was similar in both groups.
      Postoperative spirometric values were significantly better at most times with the
      paravertebral route of administration. Dependent chest tube bupivacaine losses
      were approximately four times higher in the interpleural group. CONCLUSION: Local
      anesthetic on the diaphragm might actively impair respiratory function through
      diaphragmatic and abdominal muscle weakness, while failing to contribute to pain
      relief.

PMID- 9583548
TI  - Epidural anesthesia in cardiac surgery: is there an increased risk?
AB  - OBJECTIVE: To assess the risk of hemorrhagic complications associated with
      epidural anesthesia in patients undergoing coronary artery bypass grafting.
      DESIGN: A prospective study. SETTING: A cardiac surgical center associated with a
      university. PARTICIPANTS: Five hundred fifty-eight consecutive patients scheduled
      for coronary artery bypass surgery. INTERVENTIONS: A Tuohy 18G epidural catheter
      was inserted the day before surgery in all patients. MEASUREMENTS AND MAIN
      RESULTS: Preoperative coagulation tests, such as platelet count and prothrombin
      time, were performed. No patient was on oral anticoagulation therapy or had
      coagulation disorders. Four hundred three (72%) patients were on antiplatelet
      therapy, which was terminated at least 1 week before surgery. The epidural
      catheter was left in situ for up to 5 days. All patients were observed daily for
      signs of spinal cord compromise, such as radicular back pain or progressive
      sensory or motor deficits. There were no documented spinal hematomas. CONCLUSION:
      By following certain guidelines, the risk for the development of epidural
      hematoma is not increased in patients undergoing epidural anesthesia during
      cardiac surgery.

PMID- 9583549
TI  - Early extubation after abdominal aortic reconstruction.
AB  - OBJECTIVE: To assess the safety of early (<2 hrs) extubation after elective
      infrarenal aortic surgical procedures. DESIGN: A retrospective chart review of
      192 consecutive elective infrarenal aortic surgical procedures from January 1990
      to March 1994 at Mayo Clinic Scottsdale was undertaken. MEASUREMENTS AND MAIN
      RESULTS: Combined general and epidural anesthesia was used extensively (187
      patients; 97.4%). Early extubation was accomplished in 166 (86.5%) patients. Time
      to extubation was dependent on clinical factors and not by protocol. All early
      extubations occurred in the operating room or recovery room with a median time
      from skin closure of 12 minutes. Ten patients were extubated from 2 to 12 hours
      after the procedure, 14 patients more than 12 hours after the procedure, and 2
      patients were not extubated and subsequently expired. Of the 166 patients
      extubated within 2 hours, 8 (4.8%) required reintubation. Factors found
      univariantly to be significantly associated with failure of early extubation
      include obesity, abnormal chest x-ray postoperatively, prior myocardial
      infarction, and prior coronary revascularization (p < 0.05). CONCLUSION: Early
      extubation (<2 hrs) after elective infrarenal aortic procedures may be performed
      safely and should be undertaken unless clinical features suggest failure of
      extubation.

PMID- 9583550
TI  - Propofol-based versus fentanyl-isoflurane-based anesthesia for cardiac surgery.
AB  - OBJECTIVE: To evaluate drug costs, time of mechanical ventilation, complications,
      and hospital length of stay comparing propofol-based with fentanyl-isoflurane
      based anesthesia. DESIGN: A prospective, randomized study. SETTING: A university
      affiliated, tertiary care community hospital. PARTICIPANTS: Seventy patients
      undergoing primary coronary artery bypass surgery. INTERVENTIONS: Patients were
      randomized to either a low-dose fentanyl-isoflurane or a lower-dose fentanyl
      isoflurane anesthetic supplemented with a continuous infusion of propofol.
      MEASUREMENTS AND MAIN RESULTS: Fentanyl-isoflurane anesthesia was significantly
      less expensive ($50.03+/-$27.26 v $121.69+/-$31.40) for anesthesia drugs and
      ($58.08+/-$27.39 v $129.91+/-$31.52) for total drug costs. There was also a trend
      for patients in the fentanyl-isoflurane group to be extubated slightly sooner
      (388+/-202 v 449+/-252 min) and go home sooner (5.1+/-1.8 v 6.0+/-3.0 days).
      CONCLUSION: Fentanyl-isoflurane provides an inexpensive anesthetic that permits
      as prompt an extubation as propofol, thus conserving resources for other
      patients.

PMID- 9583551
TI  - The effect of etomidate induction on plasma cortisol levels in children
      undergoing cardiac surgery.
AB  - OBJECTIVE: To investigate the effect of a single induction dose of etomidate on
      plasma cortisol and adrenocorticotrophic hormone (ACTH) levels in pediatric
      patients with congenital heart disease. DESIGN: A prospective, randomized study.
      SETTING: A university hospital. PARTICIPANTS: Thirty children undergoing
      cardiopulmonary bypass. INTERVENTIONS: Patients were randomly allocated into two
      groups to receive etomidate, 0.3 mg/kg, and fentanyl, 1 microg/kg, or ketamine, 1
      mg/kg, and fentanyl, 1 microg/kg intravenously, for anesthesia induction.
      Anesthesia was maintained with 50% nitrous oxide and 0.5% isoflurane in oxygen.
      Plasma cortisol and ACTH levels were measured on five occasions: preoperatively,
      after induction of anesthesia, after cross-clamping, at the end of surgery, and
      24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Plasma cortisol levels
      of the etomidate group decreased with anesthesia induction and remained
      significantly low during cardiopulmonary bypass, at the end of operation, and 24
      hours postoperatively. Plasma cortisol levels of the etomidate group after the
      anesthesia induction, during cardiopulmonary bypass, and at the end of the
      operation were significantly lower than the ketamine group. CONCLUSION: These
      results show that etomidate is a suitable agent for suppressing the increase in
      cortisol levels associated with the stress response caused by cardiopulmonary
      bypass in children with congenital heart defects, and can be used safely.

PMID- 9583552
TI  - One-lung ventilation in patients with difficult airways.

PMID- 9583553
TI  - Airway obstruction caused by an oleothorax.

PMID- 9583554
TI  - Anesthetic management of a patient with an obstructing carinal carcinoid for
      tumor excision and pneumonectomy.

PMID- 9583555
TI  - Delayed Horner's syndrome as a complication of continuous thoracic epidural
      analgesia.

PMID- 9583556
TI  - Acute respiratory distress after deep cervical plexus block.

PMID- 9583557
TI  - Post-lung resection pulmonary edema: a case for aggressive management.

PMID- 9583558
TI  - Echocardiography-based assessment and management of atherosclerotic disease of
      the thoracic aorta.

PMID- 9583559
TI  - Case 12-2-1998. Noncardiac surgery and pacemaker cardioverter-defibrillator
      management.

PMID- 9583560
TI  - Pro: Combined coronary and vascular surgery is better than separate procedures.

PMID- 9583561
TI  - Con: Combined coronary and vascular surgery is not better than separate
      procedures.

PMID- 9583562
TI  - Sudden hypotension before cardiopulmonary bypass.

PMID- 9583563
TI  - Early extubation after elective mitral valve surgery.

PMID- 9583564
TI  - Problems with CPAP during one-lung ventilation in thoracoscopic surgery.

PMID- 9583565
TI  - Comparison of lumbar and thoracic epidural narcotics for postoperative analgesia
      in patients undergoing abdominal aortic aneurysm repair.

PMID- 9583566
TI  - Incorrect assembly of an Arrow-Flex sheath-dilator: a potential cause of vascular
      trauma.

PMID- 9583567
TI  - Risk management in cardiac anesthesia: analysis of critical issues. Introduction.

PMID- 9583569
TI  - Resolved: A pulmonary artery catheter should be used in the management of the
      critically ill patient. Pro.
AB  - Selected studies showing both positive and negative outcomes with the use of
      pulmonary artery catheters (PACs) are reviewed. Indications for use of a PAC are
      controversial, although clearly the "red cap syndrome" is an indication for its
      insertion. There are sufficient data as well as personal experience to suggest
      that PACs do make a difference in the management of critically ill patients.
      Attention is focused on the level of physician expertise in interpreting data
      provided by PAC monitoring as the most critical limitation on the physician's
      ability to make appropriate clinical decisions. Studies are reviewed that
      addressed physician level of expertise related to PAC insertion, complications,
      data and waveform interpretation, and management. User knowledge clearly is
      suboptimal. Before attempting to draw conclusions from outcome studies, criteria
      for appropriate use need to be developed and clinician knowledge needs to be
      significantly improved.

PMID- 9583568
TI  - Central nervous system monitoring during open heart surgery: an update.
AB  - Electroencephalography (EEG) is used to monitor the function of the central
      nervous system in a variety of surgical procedures. During cardiac surgery with
      cardiopulmonary bypass, ischemic changes on the EEG as a result of impaired
      central nervous system blood supply can be noted. The EEG also may be used to
      monitor the functional state of the brain during and after profound hypothermic
      circulatory arrest. If a desired goal is to reduce cerebral metabolism using a
      barbiturate or other such agent, the EEG can be monitored to provide a measurable
      pharmacodynamic end point (burst suppression). Techniques have been developed to
      process the EEG signal using a computer and to improve on-line interpretation.
      These include fast Fourier transformation to develop a three-dimensional plot or
      compressed spectral array, evoked-potential monitoring, and bispectral analysis
      to derive a univariate descriptor of the EEG. These techniques have been used to
      detect awareness and indirect memory function, as well as to assess the adequacy
      of anesthesia. There is a good correlation between implicit memory and
      alterations in midlatency auditory-evoked responses. The bispectral index has
      been used to assess the adequacy of anesthesia as well as to detect awareness.
      Preliminary studies suggest that titrating the anesthetic to bispectral index
      levels may be useful during cardiac surgery.

PMID- 9583570
TI  - Resolved: A pulmonary artery catheter should be used in the management of the
      critically ill patient. Con.
AB  - Complications associated with pulmonary artery catheters (PACs) include
      interpretation errors, insertion problems, sepsis, thrombosis, and dysrhythmias.
      Alternatives to the use of PACs include the central venous pressure catheter,
      measurement of cardiac output by thoracic electrical bioimpedance, gastric
      tonometry and the measurement of serum lactate level, and the still to be
      released fiberoptic PCO2 sensor developed to provide a continuous measure of
      intramucosal PCO2. Outcome studies show conflicting results. Selected outcome
      studies conducted since 1987 are briefly reviewed, including studies of the use
      of PACs to achieve supranormal therapy. There are insufficient data from
      prospective, randomized, and adequately controlled studies to determine whether
      PAC use reduces mortality and morbidity rates. Until such evidence becomes
      available, a PAC should not be used routinely in critically ill patients, and its
      use should not be considered the only standard of care.

PMID- 9583571
TI  - Safety issues in heparin and protamine administration for extracorporeal
      circulation.
AB  - This article reviews past approaches to heparin and protamine dosing and
      summarizes current practice. The author elucidates his experience with the Celite
      activated coagulation time (ACT), with attention to his adoption of a value of
      400 seconds for this time; the adoption of an ACT of 480 seconds by Bull et al (J
      Thorac Cardiovasc Surg 69:674-684, 1975) and Young et al (Ann Thorac Surg 26:231
      240, 1978); the proposed use of heparin response curves by Bull et al; the
      author's experience with a unitized dosing system to individualize dosing of
      heparin; and the use for this purpose by Despotis et al (J Thorac Cardiovasc Surg
      110:46-54, 1995) of a system based on protamine titration. In more than 270 adult
      cardiac surgery patients, the unitized dosing system identified patients with
      high sensitivity or resistance to heparin and facilitated exact individualized
      doses to be given to produce the desired effect. Thus, less heparin was used in
      short bypass runs. Patients received less protamine than they would have with any
      other formula, and there was less blood loss and fewer transfusions required.
      Currently, no claims for efficacy or safety can be made for maintaining heparin
      concentrations greater than 3 U/mL. Pending further clarification, heparin dosage
      cannot be safely reduced when using heparin-bonded circuits. Aprotinin is not a
      procoagulant during cardiopulmonary bypass. Emerging studies suggest that graft
      patency is not affected by aprotinin use. The Celite ACT should not be used to
      monitor heparin effect and safety when using aprotinin; the kaolin ACT should be
      used instead.

PMID- 9583572
TI  - Cardiopulmonary bypass-induced inflammation: is it important?
AB  - The systemic endotoxemia that occurs with the institution of cardiopulmonary
      bypass (CPB) is a potent stimulus for the release of proinflammatory cytokines,
      including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and IL
      6. Raised IL-6 levels have been reported to correlate with post-CPB left
      ventricular wall-motion abnormalities and myocardial ischemic episodes.
      Neutrophil-endothelial adhesion is strongly implicated in the inflammation and
      reperfusion injury that may follow a period of CPB, and organ injury is thought
      to be, in part, neutrophil mediated. The CD11b neutrophil integrin primarily
      responsible for endothelial binding is rapidly, permanently, and preferentially
      expressed on exposure to cytokines. The endothelial ligand intercellular adhesion
      molecule-1 is also upregulated by cytokine exposure. Nitric oxide (NO)
      synthesized by the vascular endothelium can inhibit neutrophil-endothelial
      adhesion by downregulating CD11b/CD18 receptor expression and inhibit platelet
      activation. The cytokines TNF-alpha, IL-1, and endotoxin can cause the induction
      of NO synthase and the release of large amounts of NO that may cause tissue
      injury. Various treatment strategies to reduce CPB-induced inflammation provide
      evidence to support the causal relationship between CPB-activated cytokine
      release, neutrophil activation, and stimulation of increased NO synthesis. The
      significant reductions in TNF-alpha and IL-6 levels with hemofiltration during
      CPB in children are associated with improved hemodynamics and early postoperative
      oxygenation. Acadesine can inhibit the upregulation of leukocyte CD11b adhesion
      receptors, and treatment in patients before and during surgery can reduce early
      cardiac death, myocardial infarction, and combined adverse cardiovascular
      outcomes. Recent data suggest that administration of the serine protease
      inhibitor aprotinin to patients undergoing myocardial revascularization with CPB
      can reduce TNF-alpha blood levels and blunt neutrophil CD11b upregulation.
      Preliminary data suggest that aprotinin can inhibit cytokine-induced nitric oxide
      synthase expression and subsequent NO production by murine bronchial epithelial
      cells. These effects may explain some of the reported antiinflammatory effects of
      the serine protease inhibitors.

PMID- 9583574
TI  - Temperature sensitivity of the body surface over the life span.
AB  - Detection thresholds to warming and cooling were measured in 13 regions of the
      body in 60 adults aged between 18 and 88 years. From these thresholds were
      constructed maps of thermal sensitivity homologous to body maps of spatial acuity
      (in the older literature two-point discrimination), long known to the
      somatosensory scientist. Maps of cold and warm sensitivity for young, middle-aged
      and elderly adults, show how sensitivity changes with age in the various body
      regions. Three characteristics emerge, irrespective of age: (1) sensitivity
      varies approximately 100-fold over the body surface. The face, especially near
      the mouth, is exquisitely sensitive, the extremities, by comparison, poor, other
      regions, intermediate. (2) All body regions are more sensitive to cold than to
      warm. (3) The better a region is at detecting cold, the better it is at detecting
      warm. With age, thermal sensitivity declines. The greatest changes take place in
      the extremities, especially the foot, where thresholds often become too large to
      measure. Central regions give up their sensitivity with age more slowly, and even
      (as in the lips) inconsequentially. Similar age-related changes have also
      previously been shown to characterize spatial acuity.

PMID- 9583573
TI  - Contribution of C-fiber afferent nerves and autonomic pathways in the urinary
      bladder to spinal c-fos expression induced by bladder irritation.
AB  - Previous studies have revealed that chemical irritation of the urinary bladder
      and urethral mucosa increases the expression of the immediate-early gene, c-fos,
      in the lumbosacral spinal cord of the rat. The present experiments were
      undertaken to determine whether drugs known to suppress bladder reflex pathways
      or spinal nociceptive mechanisms would influence c-fos expression induced by
      chemical irritation of the lower urinary tract (LUT). Capsaicin (100 mg/kg
      subcutaneous (s.c.), 7 days prior to the experiment) which does not block bladder
      reflexes but does desensitize C-fiber afferents, reduced (89%) the number of Fos
      positive cells in the lumbosacral spinal cord induced by acetic acid-induced
      irritation of the LUT. Morphine (2.5 mg/kg, intravenous (i.v.)) or a low dose of
      baclofen, a GABA(B) agonist, both of which markedly suppressed reflex bladder
      activity, did not alter spinal c-fos expression induced by LUT irritation.
      However, a larger dose of baclofen (10 mg/kg, i.v.) reduced by 45% the number of
      Fos-positive cells. Clonidine (200 microg/kg, i.v.), an alpha2 adrenergic
      agonist, depressed bladder reflexes but produced only a small decrease (25%) in c
      fos expression in lateral laminae V-VII of the cord. The ganglionic blocking
      agent, hexamethonium, which blocks autonomic but not afferent pathways to the
      LUT, decreased c-fos expression by 50%. The results indicate that certain drugs
      can differentially affect reflex bladder activity and c-fos expression and that
      analgesic drugs which suppress somatic nociceptive pathways do not necessarily
      affect the c-fos expression induced by visceral nociceptive input.

PMID- 9583575
TI  - Factors affecting tactile spatial acuity.
AB  - Tactile spatial acuity on the fingerpad was measured using a grating orientation
      task. In this task, subjects are required to identify the orientation of square
      wave gratings placed on the skin. Previous studies have shown that performance
      varies as a function of the width of the grooves in the gratings. In the present
      study, both groove width and the overall size and configuration of the contactors
      were varied. Sensitivity improved with wider grooves and with larger contactors.
      Additional measurements showed that the improved sensitivity is not the result of
      the increase in total area contacted, but rather is due to two other factors
      associated with larger contactors. One is the greater linear extent of the larger
      contactors. The other appears to be due to the reduction in the interference
      produced by the outer edge of the contactor. Specifically, as the contactor
      increases in size, the distance between the outer edge and the center portion of
      the grooves also increases. It was also shown that subjects are more sensitive to
      a single, continuous groove as compared with two grooves of the same total length
      but spatially discontinuous. Similarly, subjects are more sensitive to a
      contactor with a continuous groove than to a contactor in which just the end
      points of the groove are presented. The results are generally consistent with the
      results of peripheral, neurophysiological recordings. The results are discussed
      in terms of the way in which both spatial and intensive factors may affect
      sensitivity to grating orientation.

PMID- 9583576
TI  - Quantification of deep and superficial sensibility in saline-induced muscle pain-
      a psychophysical study.
AB  - The aim of the present study was to study the sensibility in the area of saline
      induced muscle pain. In three experiments, ten subjects were exposed to computer
      controlled infusion of 0.5 ml isotonic (0.9%) or hypertonic (9%) saline into the
      anterior tibial muscle. The pain intensity was assessed on a visual analogue
      scale (VAS). The pain threshold (PT) to pressure and electrical stimulation in
      muscle and subcutaneous tissues was determined. Three experiments were performed
      in which infusion of hypertonic saline produced significantly higher VAS scores
      than isotonic saline. In all three experiments, there was no significant
      difference in PT obtained after infusion of isotonic saline compared with
      infusion of hypertonic saline. In experiment 1, the PT was determined at the
      infusion site and 4 cm from the infusion site. At the infusion site, the pressure
      PT decreased (-19 +/- 2%) 1, 3, 5, 7 and 9 min after infusion of isotonic and
      hypertonic saline, but remained unchanged 4 cm from the infusion site. The
      intramuscular electrical PT at the infusion site and 4 cm from the infusion site
      increased significantly (29 +/- 6%) 5, 7 and 9 min after saline infusion. In
      experiment 2, the pressure PT and the intramuscular electrical PT were recorded
      after two infusions of saline separated by 1 day. The day after the first
      infusion, the pressure PT was decreased compared with the PT before the first
      infusion, but the electrical PT was not affected. Moreover, the hypertonic saline
      infusion given on the second day produced significantly higher (130 +/- 50%) VAS
      scores than the infusion given on the first day. In experiment 3, the PT was
      determined in the subcutaneous tissue, but no significant effects of saline
      infusion were found. The present placebo-controlled experiments failed to show
      muscular or subcutaneous hyperalgesia after saline-induced muscle pain per se.

PMID- 9583577
TI  - Vertebral axial decompression therapy for pain associated with herniated or
      degenerated discs or facet syndrome: an outcome study.
AB  - The outcomes of vertebral axial decompression (VAX-D) therapy for patients with
      low back pain from various causes are reported. Data was collected from twenty
      two medical centers for patients who received VAX-D therapy for low back pain,
      which was sometimes accompanied by referred leg pain. Only patients who received
      at least ten sessions and had a diagnosis of herniated disc, degenerative disc,
      or facet syndrome, which were confirmed by diagnostic imaging, were included in
      this study; a total of 778 cases. The average time between the initial onset of
      symptoms and the beginning of this therapy was 40 months, and it was four months
      or more in 83% of the cases. The data contained the patients' quantitative
      assessments of their own pain, mobility, and ability to carry out the usual
      'activities of daily living'. The treatment was successful in 71% of the 778
      cases, when success was defined as a reduction in pain to 0 or 1, on a 0 to 5
      scale. Improvements in mobility and activities of daily living correlated
      strongly with pain reduction. The causes of back pain and their relationship to
      this therapy are also discussed.

PMID- 9583578
TI  - Clinical applicability of functional magnetic resonance imaging and activation
      study with single photon emission computerized tomography for functional mapping.
AB  - The purpose of this study is to estimate the clinical applicability of functional
      magnetic resonance imaging (f-MRI) combined with the activation study using
      single photon emission computerized tomography (SPECT) with special reference to
      identification of primary sensorimotor area. Five healthy volunteers and 5
      patients with brain tumors located around the sensorimotor cortex were studied by
      both f-MRI with gradient echo and SPECT with 99mTc-ethyl cysteinate dimer using
      split-dose and subtraction method. In f-MRI study, the significant activation of
      the sensorimotor area was observed in all subjects. Various concurrent activation
      regions such as supplementary motor (2 volunteers vs. 4 patients), premotor (1
      vs. 2) and ipsilateral sensorimotor area (1 vs. 2) were also observed. In the
      cases with the activation of neighboring regions of sensorimotor area, it was
      difficult to identify the area in f-MRI. In SPECT study, the sensorimotor area
      was depicted as the most increased area in regional cerebral blood flow in eight
      cases, the characteristics of which were helpful to diagnose the area, while
      significant activation of the area with edema could not be detected in two
      patients. Consequently, the sensorimotor area was cross-validated with both the
      modalities. This study demonstrated that it would be valuable to use both
      techniques for the clinical assessment of the sensorimotor area.

PMID- 9583579
TI  - Influence of transducer frequency on Doppler microemboli signals in an in vivo
      model.
AB  - The purpose of this study was the comparison between 1 MHz and 2 MHz transducers
      in the detection of Doppler microembolic signals (MES). Intraoperative monitoring
      was performed over the arterial tubing of the extracorporal circulation circuit
      in 10 patients undergoing coronary artery bypass surgery, using a pulsed
      ultrasound machine (DWL X-4). 1 MHz and 2 MHz probes were mounted to insonate
      sequential tubing segments and all monitoring sessions saved on digital audio
      tapes (DAT). MES counts and intensity as detected by each probe were subsequently
      evaluated. Specific interobserver agreement was assessed using Cohen's kappa
      statistic. Time delay in the appearance of MES between the transducers was
      minimal (0-0.1 msec). A total of 5293 (64%) MES were detected by both probes,
      2796 (33.8%) only with the 1 MHz and 181 (2.2%) only with the 2 MHz probe.
      Significant differences in MES intensity were evident when comparing the 1 MHz to
      the 2 MHz transducer (16.4 +/- 0.1 and 11 +/- 0.1 dB with the 1 MHz and 2 MHz
      transducers respectively, p < 0.0001). Specific interobserver agreement was
      satisfactory (k = 0.78). Use of 1 MHz instead of 2 MHz transducers increases the
      yield of embolus detection in vitro. Evaluation of the applicability and
      performance of this transducer in clinical settings is warranted.

PMID- 9583580
TI  - Microsurgical anatomy of the suboccipital segment of the vertebral artery.
AB  - The craniocervical regions of seven cadavers (14 sides) injected with silicone
      rubber were dissected under a Zeiss OPMI surgical microscope. The present study
      provides a detailed description of the suboccipital segment of the vertebral
      artery, with particular attention to its loops, branches, supporting osteofibrous
      structures, adjacent nerves, and surrounding venous structures. Several ligaments
      fixating the vertebral artery to surrounding structures, which have not been
      described in previous anatomical studies, were found. The authors propose an
      anatomically based subdivision of the suboccipital segment of the vertebral
      artery into five subsegments: infraforaminal, foraminal, supraforaminal,
      horizontal, and intramembranous. Measurements of surgically and clinically
      important features were obtained. Surgical approaches to this region are
      suggested based on a more informed understanding of the local anatomy.

PMID- 9583581
TI  - Microsurgical anatomy of the short central artery.
AB  - We studied the origin, length, external diameter, disposition, branching patterns
      and the perforators of short central artery in the circle of Willis in eighty
      fresh, unfixed cerebral hemispheres (40 brains). We also examined the
      relationship of the short central artery, the recurrent artery of Heubner, and M1
      perforators to the anterior perforated substance, caudate and putamen. The short
      central artery arises at 5.2 +/- 3.36 mm from the origin of the anterior cerebral
      artery, hidden and overlapped by the internal carotid artery bifurcation. The
      recurrent artery of Heubner arises distally to the origin of the short central
      artery. Four main anatomical variations were found: 1. Presence of short central
      artery and recurrent artery of Heubner (37.5%). 2. Isolated presence of the short
      central artery (27.5%). 3. Isolated presence of the recurrent artery of Heubner
      (21.25%). 4. Absence of short central artery and recurrent artery of Heubner
      (13.75%). Two different branching patterns were observed: 1. 2-4 straight
      perforators from the short central artery, perforators from the recurrent artery
      of Heubner and lenticulostriate from the most medial portion of the M1, in 42 of
      80 hemispheres (52.5%). 2. 8-10 perforators from only short central artery in 10
      of 80 hemispheres (12.5%) with absent or hypoplastic recurrent artery of Heubner
      and lenticulostriates from M1 and M2.

PMID- 9583582
TI  - Risk Score Estimation: a new method to determine optimal timing of aneurysm
      clipping for improved management outcome.
AB  - The outcome of 703 patients who underwent surgery following aneurysmal
      subarachnoid hemorrhage were analyzed with regards to age, associated medical
      conditions, vasospasm and clinical status at the time of operation. Patients with
      Hunt and Hess grade I, II, and III had a 96%, 90% and 93% favorable (good and
      fair) outcome respectively. In contrast only 58% of patients with grade IV had
      the same result. The outcome was unfavorable in 13% of the patients who were
      older than 60 years of age and only in 9% of the patients between 30-59 years of
      age. All the patients younger than 30 years old had a good outcome. Associated
      medical condition increased the incidences of poor outcome (7% vs. 12%). Patients
      harboring vertebro basilar aneurysms had a poorer outcome, as opposed to those
      with aneurysms located in the anterior circulation (20% vs. 8%). The presence of
      angiographic vasospasm alone did not influence outcome. A proposed point value
      was given for each of the adverse factors and from this the optimal surgical time
      was determined for each individual patient. This concept of Risk Score Estimation
      approach may improve the management outcome of patients with ruptured
      intracranial aneurysms.

PMID- 9583583
TI  - Correlation between intracranial pressure (ICP) and changes in CT images of
      cerebral hemorrhage.
AB  - The relationship between intracranial pressure and CT images was investigated in
      80 cases of cerebral hemorrhage that occurred between 1984 and 1990. In traumatic
      intracerebral hematoma, positive correlation was found between intracranial
      pressure and both shift of midline structures and volume of hematoma except in
      the occipital lobe or at the base of the frontal lobe. In nontraumatic
      intracerebral hematoma, increased intracranial pressure was found to correlate
      with changes in the configuration of the lateral ventricles, intraventricular
      hemorrhage, and compression of the basal cisterns and cortical sulci. No
      correlation between intracranial pressure and hematoma volume was observed, most
      likely due to the number of elderly patients in the subject population. In
      nontraumatic subarachnoid hemorrhage, positive correlation existed between
      increased intracranial pressure and intraventricular hemorrhage as well as Evans'
      ratio calculated using repeat CT images that were obtained due to disturbances in
      cerebrospinal fluid circulation. These results suggest that the degree by which
      intracranial pressure increases in patients with cerebral hemorrhage can be
      estimated by the changes in CT images.

PMID- 9583584
TI  - Hemodynamics of stroke patients under therapy with low molecular weight
      hydroxyethyl starch.
AB  - In stroke penumbra perfusion depends passively on hemodynamics. So far
      hemodynamic effects of low molecular weight hydroxyethylstarch (HES) has not been
      investigated. Ten stroke patients received hypervolemic HES therapy. Cardiac
      output and heart rate were monitored using the bioimpedance method, blood
      pressure by conventional measurement. The Scandinavian Stroke Scale assessed
      clinical outcome. Circadian cardiac output changes were measured in 20 controls.
      Patients' cardiac output increased after the loading dose (5.3 +/- 1.4 l min(-1)
      to 6.5 +/- 1.7 l min(-1), p < 0.01), fluctuating then between 5 and 7 l min(-1)
      without nocturnal decrease. Beside an initial increase, the heart rate showed,
      like blood pressure, no remarkable changes. The Scandinavian Stroke Scale score
      did not change significantly. The controls showed a circadian cardiac output
      fluctuation (2.00 am, 5.3 +/- 0.3 l min(-1); 8.30 am, 8.1 +/- 0.6 l min(-1). Our
      patients showed a hemodynamic and clinical stabilization under therapy with low
      molecular weight HES. The physiological nocturnal decrease of cardiac output and
      blood, which might cause clinical deterioration in stroke patients, was avoided.

PMID- 9583585
TI  - Magnetic source imaging of the sensory cortex on the surface anatomy MR scanning.
AB  - Surgery for lesions either within or close to the central sulcus of the brain
      always carries the risk of inducing iatrogenic motor or sensory deficits. We
      performed advanced magnetic source imaging (MSI) of the somatosensory cortex
      combined with 3-dimensional (3-D) surface anatomy scanning (SAS) of magnetic
      resonance imaging on 9 patients who had peri-Rolandic lesions, including 7 tumor
      cases, 1 arteriovenous malformation and 1 focal cortical dysplasia. 3-D MSI
      mapped out the entire somatosensory homunculus and localized the lesion on a
      cortical surface image. The results were then used for developing an appropriate
      surgical strategy and also as a reference in the operating room. This
      relationship and deduced localization were both confirmed by a cortical recording
      of the somatosensory evoked potentials at the time of surgery. Case histories of
      selected patients are briefly reported to demonstrate how the method can be used
      to improve the safety of surgical excisions of peri-Rolandic lesions. MSI on SAS
      including the cortical veins, was thus found to provide a readily interpretable
      presurgical road map of the cortical surface which compares favorably to that of
      intraoperative brain mapping.

PMID- 9583586
TI  - Microvascular decompression of the cochlear nerve in patients with severe
      tinnitus. Preoperative findings and operative outcome in 22 patients.
AB  - We evaluated the operative outcome in 22 consecutive patients who underwent
      microvascular decompression (MVD) of the intracranial portion of the cochlear
      nerve to relieve incapacitating tinnitus and related it to preoperative findings.
      The patients were selected for operation from the following criteria: severe
      tinnitus with sensorineural hearing loss and/or changes in brainstem auditory
      evoked potentials (BAEPs). Fifty percent had unilateral tinnitus. Before
      operation, 17 patients (77%) had sensorineural hearing loss in their affected
      ear. BAEPs were abnormal in 21 patients (95%) and acoustic middle ear reflex
      response was abnormal in six patients (27%). Vascular compression of the cochlear
      nerve was found in all patients during the operation. After the operation, 33%
      had relief of their tinnitus (two patients were totally free of tinnitus and five
      were markedly improved). Eight patients were slightly improved (38%), and the
      tinnitus did not change in four patients; two patients (10%) became worse. Of the
      patients with unilateral tinnitus, 63% had relief of their tinnitus. In one
      patient hearing was noticeably improved after the operation. Five patients (23%)
      had mild to moderate sensorineural hearing loss due to the operation. No other
      complications were detected.

PMID- 9583587
TI  - Pial arteriovenous malformation with massive perinidal edema.
AB  - It is generally considered that perinidal edema in an arteriovenous malformation
      (AVM) is caused by a concomitant intracerebral hematoma. We report a rare case of
      AVM with perinidal massive edema which was possibly not due to hemorrhage, and
      discuss the pathophysiological mechanisms of such edema development. A 60-year
      old woman presented with a sudden onset severe headache. Computed tomography (CT)
      scans obtained two hours after the onset showed an AVM-like lesion with a small
      hematoma in the right parieto-occipital lobe, and unexpectedly early development
      of massive edema adjacent to the hematoma. Angiograms demonstrated a medium-sized
      AVM, and severe stenosis in the draining vein which suggested the presence of
      venous hypertension at prestenotic sites. Repeated CT scans and magnetic
      resonance (MR) images in the chronic period after the hemorrhage demonstrated
      persistence of the perinidal edema with mass effect. Removal of the lesion was
      achieved 2 months after the onset. MR images 3 months after the operation showed
      marked reduction of perinidal edema. The time course of the perinidal edema
      suggests that its development was unrelated to the hemorrhage. The findings
      indicate that increased venous pressure secondary to severe stenosis of the
      draining vein may possibly contribute to the development of perinidal edema.

PMID- 9583588
TI  - The effect of lesionectomy and the perilesional GABAergic neuronal changes in
      alumina cream-induced focal motor epilepsy in cats.
AB  - The effect of lesionectomy depends on the reversibility of the epileptogenic
      changes in the perilesional cortex. We studied how the perilesional GABAergic
      neuronal changes are related to the effect of lesionectomy in the alumina cream
      induced focal epilepsy model in cats. Sequential changes of GABAergic neurons and
      spike activities were measured after the micro-injections of alumina cream (AC).
      Alumina granulomas were excised 15 days and 40 days after the injections. At day
      20 following the AC injection, GABAergic neurons were decreased 25 to 40%
      compared with those in the contralateral intact cortex. At day 40, a significant
      increase of spike activities occurred. GABA positive cells were decreased more
      than 50% compared with those in the contralateral cortex. At day 80, significant
      cell loss in perilesional cortex was demonstrated. The effect of lesionectomy was
      greater in the early excised group than in the late excised group. Decrease of
      GABAergic neuron was more severe in the late excised group compared to the early
      excised group. Our results indicate that more than 50% reduction of perilesional
      GABA neurons may be a critical point in epileptogenesis in this model.
      Lesionectomy alone prior to a 50% reduction in perilesional GABAergic neurons may
      be sufficient for seizure control. With these data it is still unclear whether
      these findings contribute to the choice between lesionectomy alone and
      lesionectomy with resection of the perilesional cortex. Further study is needed
      to understand the difference between the AC epilepsy model and human chronic
      epilepsy.

PMID- 9583589
TI  - Effects of isoproterenol on blood-brain barrier permeability in rats.
AB  - This study was performed to examine whether the direct topical application of
      isoproterenol to the cerebral cortex could modify the blood-brain barrier (BBB)
      permeability and whether this effect could be blocked by Timolol, a beta
      adrenergic receptor antagonist without a membrane stabilizing effect. After a
      craniotomy in each animal, a low-dose (10(-4) M, n = 6) or a high-dose (10(-3) M,
      n = 6) isoproterenol patch was placed on one cortex (Ipsilateral Cortex: IC) and
      a normal saline patch was placed on the other cortex (Control Cortex: CC).
      Another 6 animals were pretreated with Timolol 1.5 mg kg(-1) i.v. before the
      placement of high dose isoproterenol patches. The BBB transfer coefficient (Ki)
      was determined using 14C-alpha-aminoisobutyric acid. Mean arterial blood pressure
      decreased after low- and high-dose isoproterenol patches. The low- and high-dose
      of isoproterenol increased Ki by 58% (IC: 5.94+/-2.02, CC: 3.77+/-1.75 microl g
      min(-1)) and 66% (IC: 6.97+/-3.66, CC: 4.19+/-2.48 microl g min(-1)) respectively
      when compared to that of the corresponding CC. Pretreatment with Timolol
      prevented the increase of the Ki by a high-dose of isoproterenol (IC: 5.33+/
      1.88, CC: 5.66+/-1.72 microl g min(-1)). Our data demonstrate that a direct
      application of a beta-adrenergic receptor agonist to the brain parenchyma
      increased the permeability of the BBB, and that this effect could be prevented
      with a beta-adrenoceptor antagonist.

PMID- 9583590
TI  - Intraluminal suture occlusion of the middle cerebral artery in Spontaneously
      Hypertensive rats.
AB  - In models of middle cerebral artery occlusion using intraluminal suture, the size
      and the distribution of ischemic injury vary considerably among laboratories. In
      transcranial models of cerebral ischemia, a more consistent cerebral ischemic
      lesion is seen in Spontaneously Hypertensive rats (SHR). In the present study, we
      performed intraluminal suture occlusion of the MCA in SHR and compared its
      reproducibility with those in Sprague-Dawley (SD) rats. Male SHR and SD rats were
      anesthetized with halothane and subjected to 2 h of temporary middle cerebral
      artery occlusion by an intraluminal suture. Comparisons of regional cerebral
      blood flow figures taken throughout the experiment and lesion volume figures
      taken at 24 h after occlusion were made between the two groups. Total lesion
      volume in the SHR group was 263.6+/-30.5 mm3 (mean +/- SD), significantly larger
      and less variable than that in the SD group (145.4+/-123.7 mm3, p < 0.02).
      Throughout the ischemic period there was a tendency for rCBF to be lower in the
      SHR group than in the SD group. In some animals of both groups, recirculation
      could not be produced by withdrawal of the suture from the ICA. The mortality
      rate was 9% in the SD group and 17% in the SHR group. Intraluminal MCA occlusion
      in SHRs is associated with a more consistent, reliable and reproducible volume of
      ischemic injury. In the studies of temporary focal cerebral ischemia, this model
      must be accompanied by the monitoring of regional cerebral blood flow so as to
      obtain more reliable results.

PMID- 9583591
TI  - Acidic fibroblast growth factor rescues gerbil hippocampal neurons from ischemic
      apoptotic death.
AB  - Neurotrophic factors have been shown to support the survival of injured neurons
      and promote their recovery. Here, we investigated whether acidic fibroblast
      growth factor (aFGF) could modify programmed cell death caused by transient
      forebrain ischemia in the gerbil. The data show that systemic administration of
      2.6 microg aFGF after 5 min ischemia followed by 7 days of brain reperfusion
      significantly (p < 0.05) reduced the occurrence of apoptotic cell death in CA1
      neurons. These data suggest that aFGF would contribute to brain protection after
      acute stroke.

PMID- 9583592
TI  - Indinavir-associated lipodystrophy.
AB  - BACKGROUND: Lipodystrophies are rare cutaneous disorders characterized by the
      symmetrical loss of subcutaneous fat from the body surface. The cause of
      lipodystrophy is not known, but a possible genetic predisposition is likely and
      either overt diabetes mellitus or insulin resistance are often associated. DESIGN
      AND METHODS: Case study. PATIENTS: Eight patients who developed either partial or
      generalized lipodystrophy after protease inhibitor therapy. RESULTS: In all eight
      patients lipodystrophy occurred after 2-12 months of starting indinavir and was
      not preceded by weight loss or inflammatory skin disease. Short-term follow-up
      after withdrawal of therapy showed no change in the patients' appearance. One
      patient developed glycosuria as lipodystrophy became manifest. In three cases
      glucose tolerance test was performed revealing a high level of insulin between
      the first and third hour of loading. CONCLUSIONS: In our view, lipodystrophy is
      an unwanted side-effect of protease inhibitor therapy causing noticeable
      disfigurement.

PMID- 9583593
TI  - Systematic review of hormonal contraception and risk of HIV transmission: when to
      resist meta-analysis.

PMID- 9583594
TI  - Serological detection of attenuated HIV-1 variants with nef gene deletions.
AB  - OBJECTIVE: To investigate whether members of a transfusion-linked cohort (the
      Sydney Bloodbank Cohort) infected with a nef-deleted strain of HIV-1 could be
      differentiated from individuals infected with wild-type strains of HIV-1 by
      characterizing the Nef antibody response of cohort members. DESIGN: Retrospective
      and prospective analysis of the nef gene sequence and the antibody response to
      Nef peptides in HIV-infected subjects. METHODS: Plasma was obtained from all
      individuals of the Sydney cohort, and from a variety of HIV-1-infected and
      uninfected controls. Antibodies recognizing full-length recombinant HIV-1NL43 Nef
      protein and synthetic peptide analogues were assessed by enzyme-linked
      immunosorbent assay. RESULTS: All 34 individuals infected with wild-type HIV-1
      had antibodies reacting with full-length Nef protein as well as with a series of
      synthetic peptides (6-23-mers) spanning most of the Nef protein of HIV-1NL43.
      Although the HIV-1 quasispecies infecting the Sydney cohort had a consensus
      deletion of the nef gene corresponding to amino-acids 165-206, HIV-1 strains from
      individual members of the cohort had additional deletions comprising up to 80% of
      the nef gene. Members of the cohort had antibodies to peptides homologous to all
      regions of the Nef protein tested, except for a single peptide (amino-acids 162
      177) that lies within the consensus nef deletion for the cohort quasispecies.
      CONCLUSION: These data show that nef-deleted strains of HIV-1 can be detected
      serologically. In the Sydney cohort, detection of antibodies to all regions of
      Nef tested, except that corresponding to amino-acids 162-177, suggests that
      observed deletions outside this domain occurred after this virus had infected
      these subjects and stimulated an immune response. A Nef peptide serological assay
      may be useful for identifying further examples of individuals infected with nef
      deleted, attenuated HIV-1 quasispecies and for assessing the evolution of those
      variants in vivo.

PMID- 9583595
TI  - Early modification of host cell gene expression induced by HIV-1.
AB  - OBJECTIVE: Characterization of the effects of infection with HIV-1 on cellular
      gene expression. DESIGN AND METHODS: Differential RNA display was applied to
      compare uninfected and HIV-1LAI-infected CEM cells 24 h post-inoculation.
      Differential bands were selected, cloned and several clones per band were
      sequenced. RNase protection assay was used to confirm differential display
      findings in HIV-1LAI-infected CEM cells as well as in another T-cell line (H9)
      infected with a different strain (HIV-1 SF33) RESULTS: Twelve differentially
      expressed bands, six up- and six downregulated in HIV-infected cells compared
      with controls, were selected. Four of the six upregulated bands were HIV
      transcripts. RNase protection assay of the remaining eight bands confirmed
      differential expression of four genes, including induction of a mariner
      transposase and moesin as well as suppression of alpha-nascent polypeptide
      associated complex and mitochondrial heat shock protein 75 in HIV-1-infected cell
      cultures. Furthermore, a significant increase of glioma pathogenesis-related
      protein was found by RNase protection assay. CONCLUSIONS: Based on this initial
      limited differential display analysis, it was estimated that expression of 3% of
      the host genes was altered by HIV-1. Amongst the identified gene modifications,
      the induction of a mariner transposase may alter cellular gene expression itself,
      whilst the enhanced expression of glioma pathogenesis-related protein suggests a
      role in the host cell response to viral infection. The increase in moesin may
      facilitate viral budding and uptake. Furthermore, the suppression of alpha
      nascent polypeptide-associated complex may promote translocation of HIV-1
      polypeptides into the endoplasmic reticulum, whereas the downregulation of
      mitochondrial heat shock protein 75 may contribute to a cytopathic effect on
      mitochondria and possibly impairs antigen presentation.

PMID- 9583596
TI  - Cross-clade recognition of p55 by cytotoxic T lymphocytes in HIV-1 infection.
AB  - OBJECTIVES: To evaluate cross-clade recognition of p55 antigen by cytotoxic T
      lymphocytes (CTL) in persons infected with diverse clades of HIV-1; to facilitate
      the development of a CTL-inducing vaccine to prevent transmission of multiple
      clades of HIV-1. DESIGN: Experiments were designed to evaluate whether persons in
      Uganda and the United Kingdom, infected with diverse clades of HIV-1, have CTL
      capable of recognizing and killing autologous target cells infected with
      recombinant vaccinia viruses (rVV) expressing the Gag protein from A, B, C and D
      clade HIV-1. The extent of cross-reactivity within such individuals, each
      infected with characterized virus, might reflect the type of cross-reactive
      immune response inducible by a monovalent vaccine. METHODS: Asymptomatic HIV
      positive individuals were fully tissue-typed by ARMS (amplification of refractory
      mutation system) polymerase chain reaction. rVV expressing the Gag protein from
      identified A, B, C and D viruses were prepared. CTL were cultured and tested for
      cytolytic activity on autologous rVV-infected or peptide-pulsed B cells. RESULTS:
      Ugandan patients had inducible CTL responses recognizing A, B, C and D clade HIV
      1 Gag. The majority of UK patients had inducible CTL responses that recognized
      two or more clades. No patient showed any HIV-2 cross-reactivity. Cross-reactive
      responses were characterized in three Ugandan patients. CONCLUSIONS: Most
      patients tested mounted cross-reactive CTL responses that recognized Gag proteins
      from clades of HIV-1 other than those with which they were infected.

PMID- 9583597
TI  - Measurement of viral sequences in cerebrospinal fluid of AIDS patients with
      cerebral white-matter lesions using polymerase chain reaction.
AB  - OBJECTIVES: To optimize the use of polymerase chain reaction (PCR) on
      cerebrospinal fluid (CSF) for the evaluation of central nervous system (CNS)
      white-matter lesions that along with clinical findings and magnetic resonance
      imaging (MRI) can allow a definite diagnosis to be made; also to evaluate
      treatment with zidovudine plus foscarnet. DESIGN AND METHODS: Fifteen AIDS
      patients with uncertain CNS white-matter lesions were identified. HIV-1 RNA,
      cytomegalovirus (CMV) and JC virus (JCV) DNA were measured in a total of 29 CSF
      samples. The results were correlated with clinical and MRI findings and treatment
      with zidovudine plus foscarnet was evaluated. RESULTS: Four and five out of 15
      patients with CMV DNA > or = 1 : 625 and JCV DNA > or = 10(3) copies/microl
      detected in the CSF were diagnosed with CMV and progressive multifocal
      leukoencephalopathy (PML), respectively. Six patients who were CMV/JCV-negative
      with the highest levels of HIV RNA (median, 6.87 log10 copies/ml) in CSF were
      considered as having HIV-1 encephalitis. Neurological symptoms were non
      supportive for diagnosis as was MRI in 11 out of 15 patients. Nine patients
      completed a 21-day course of zidovudine plus foscarnet. HIV RNA decreased
      irrespective of neurological diagnosis. All three HIV-1 encephalitis patients and
      two out of three patients with CMV leukoencephalopathy improved. In these two
      latter patients, relief of clinical symptoms coincided with decreased CMV DNA.
      JCV DNA remained unchanged and all three PML patients deteriorated. CONCLUSIONS:
      Measurement of CSF viral sequences supports the diagnosis of CNS white-matter
      lesions in AIDS patients. While effective therapy for PML remains elusive,
      treatment including zidovudine plus foscarnet may be a promising option for HIV-1
      and CMV-related manifestations.

PMID- 9583598
TI  - Early manifestations (pre-AIDS) of HIV-1 infection in Uganda.
AB  - OBJECTIVES: To describe the early manifestations of HIV-1 infection before the
      development of AIDS, in a rural Ugandan population. METHODS: Three monthly follow
      up of HIV-1-infected and uninfected participants in an HIV-1 natural history
      cohort from the start of the cohort in 1990 to the end of 1996. RESULTS: A total
      of 107 persons with prevalent infection and 104 persons with incident infection
      were enrolled. Eighty (75%) prevalent and 89 (86%) incident individuals were
      asymptomatic on enrollment. Of the 91 persons with incident infection seen within
      2 years of their estimated date of seroconversion, 51% [95% confidence interval
      (CI), 40-61] were still asymptomatic 2 years after seroconversion. At 4 and 5
      years after seroconversion, only 26% (95% CI, 17-36) and 11% (95% CI, 4-22),
      respectively, remained asymptomatic. A total of 89 participants entered World
      Health Organization (WHO) stage 2, and their main stage-defining conditions were
      weight loss <10% (and > 5%) and minor mucocutaneous manifestations. The median
      CD4 lymphocyte count for participants entering WHO stage 2 was 516 x 10(6)
      cells/l (interquartile range, 360-884 x 10(6)/l). A total of 94 participants
      entered WHO stage 3 and the main reasons were weight loss >10%, unexplained
      chronic diarrhoea, fever for more than 1 month, and severe bacterial infection.
      The median CD4 lymphocyte count for participants entering WHO stage 3 was 428 x
      10(6) cells/l (interquartile range, 276-736 x 10(6)/l). The rates of all
      conditions reported under the WHO staging system were significantly more frequent
      in HIV-positive persons than HIV-negative controls with the exception of fever
      for more than 1 month and oral hairy leukoplakia (which was seen in only three
      individuals). CONCLUSION: These are the first data from a non-selected African
      population describing the early manifestations of HIV infection. The main early
      manifestations were weight loss, minor mucocutaneous features, chronic diarrhoea,
      chronic fever and severe bacterial infections. The apparent rapid development of
      HIV-related signs and symptoms is probably indicative of the high background
      level of these conditions in our study area, as reflected by the rates of these
      conditions in the HIV-negative controls.

PMID- 9583599
TI  - Effect of combination antiretroviral therapy upon rectal mucosal HIV RNA burden
      and mononuclear cell apoptosis.
AB  - BACKGROUND: Pathogen-negative diarrhea is common in HIV infection and has been
      associated with clinical symptoms, histopathology, HIV expression, CD4+
      lymphocyte depletion, cytokine mRNA expression, and apoptosis of lamina propria
      mononuclear cells. OBJECTIVES AND METHODS: To examine the short-term (7-day)
      effects of treatment with combination antiretroviral therapies upon
      gastrointestinal symptoms and rectal mucosa in 15 HIV-infected subjects. RESULTS:
      Treatment was associated with significant decreases in the perception of
      abdominal bloating and cramps. Similar declines in RNA burden and rises in CD4+
      lymphocyte counts were found in blood and mucosa. Treatment was also associated
      with a fall in the number of lamina propria mononuclear cells undergoing
      apoptosis by in situ labeling, a change that correlated with the change in
      mucosal viral burden. CONCLUSIONS: Peripheral blood and mucosal compartments are
      equally responsive to effective antiretroviral therapies. The detection of
      significant changes within 7 days of starting antiviral therapy implies that
      intestinal dysfunction may be a direct result of local HIV infection.

PMID- 9583600
TI  - Cytomegalovirus polymerase chain reaction viraemia in patients receiving
      ganciclovir maintenance therapy for retinitis.
AB  - OBJECTIVES: To determine whether recurrence of polymerase chain reaction (PCR)
      viraemia during maintenance ganciclovir for cytomegalovirus (CMV) retinitis
      correlates with (i) CMV disease at a new anatomical site, (ii) progression of the
      presenting retinitis, or (iii) acquisition of genetic changes in gene UL97
      associated with resistance to ganciclovir. DESIGN: A previously described cohort
      of 45 patients presenting with first episode retinitis was followed clinically
      using ophthalmoscopy and serial tests for PCR viraemia for a median of 7 months.
      CMV viral load and genetic markers of ganciclovir resistance were measured in PCR
      positive samples. METHODS: PCR amplification of the glycoprotein B region of CMV
      and quantitative competitive PCR assays were employed. Genetic changes in UL97
      were identified by sequencing/point mutation assay. RESULTS: PCR viraemia
      correlated significantly with new episodes of CMV disease (P=0.011) and a trend
      was seen for the association with progression of retinitis (P=0.07). Amongst the
      14 patients PCR-positive during maintenance ganciclovir, 10 (71%) had genetic
      markers of resistance. None of these patients became PCR-negative in blood after
      reinduction ganciclovir therapy compared with three out of four without markers
      of resistance (P=0.022). CONCLUSIONS: CMV PCR viraemia correlated strongly with
      the development of new episodes of CMV disease. Most patients with progression of
      retinitis remained PCR-negative in blood, consistent with therapeutic failure due
      to poor intraocular penetration of ganciclovir. However, the minority who were
      PCR-positive in blood may have reinfected their eye, and frequently had markers
      of ganciclovir resistance. The implications of these findings for the management
      of patients with CMV disease are discussed.

PMID- 9583601
TI  - Increasing survival in AIDS patients with cytomegalovirus retinitis treated with
      combination antiretroviral therapy including HIV protease inhibitors.
AB  - OBJECTIVE: To assess the effect of combination antiretroviral therapy including
      HIV protease inhibitors on the survival of patients with cytomegalovirus
      retinitis (CMVR). DESIGN AND PARTICIPANTS: A longitudinal study of patients with
      CMVR diagnosed between October 1992 and May 1996 and followed to May 1997.
      SETTING: UK National Health Service specialist HIV medicine department. OUTCOME
      MEASURE: Time to death from first diagnosis of CMVR. Data were censored on 31 May
      1997. RESULTS: Data were available on 147 patients with CMVR. Median survival of
      CMVR patients before December 1995 was 256 days [95% confidence interval (CI),
      197-315]. Following the introduction of protease inhibitors in December 1995 this
      rose to 555 days (95% CI, 351-759). By 31 May 1996 median survival for the entire
      group of patients alive with CMVR had risen to 720 days (95% CI, 551-889). The
      mean survival after CMVR diagnosis was 224 days (n=89; 95% CI, 186-261; 1-year
      survival, 16%) in those who took no further antiretroviral therapy, 353 days in
      those who took nucleoside reverse transcriptase inhibitors but no protease
      inhibitors (n=34; 95% CI, 289-418; 1 -year survival, 50%), and 914 days in those
      who took a protease inhibitor (n=24; 95% CI, 768-1059; 1-year survival, 83%; P <
      0.0001). Multivariate analysis showed that the strongest independent predictor of
      improved survival was having ever received a protease inhibitor after CMVR
      (relative risk of death, 0.063; 95% CI, 0.027-0.149; P < 0.0001). CONCLUSIONS:
      The use of HIV protease inhibitors in combination antiretroviral therapy has been
      associated with a marked increase in the survival of patients with CMVR.

PMID- 9583602
TI  - The antiviral effect of ritonavir and saquinavir in combination amongst HIV
      infected adults: results from a community-based study.
AB  - OBJECTIVE: To characterize the antiviral effect and predictors of response to
      ritonavir and saquinavir-based antiretroviral combination therapy. DESIGN: Intent
      to-treat analysis with suppression of plasma viral load to levels below 2.7 log10
      copies/ml as the main outcome measure. PATIENTS: All adult HIV-positive
      individuals in the province of British Columbia who started taking ritonavir and
      saquinavir (each at 600 mg twice daily) in combination from 1 September 1996 to
      28 February 1997, with a minimum of two plasma viral load measurements, one at
      baseline and one after the initiation of therapy. RESULTS: A total of 58
      participants were prescribed ritonavir and saquinavir. The median plasma viral
      load at entry was 4.80 log10 copies/ml (interquartile range, 4.51-5.15 log10
      copies/ml). A total of 29 (50%) subjects demonstrated a decrease in plasma viral
      load to levels below 2.7 log10 copies/ml. This level of suppression was
      associated with higher baseline CD4 cell counts (P=0.022) and no prior exposure
      to protease inhibitors (P=0.001). After controlling for baseline CD4 cell count
      and plasma viral load, participants naive to protease inhibitors were almost
      seven times (odds ratio, 6.99; 95% confidence interval, 1.85-26.39; P=0.004) more
      likely to suppress their plasma viral load to below 2.7 log10 copies/ml than
      those who had previously used protease inhibitors. CONCLUSION: Our analysis
      demonstrates that a ritonavir and saquinavir-based combination can produce a
      substantial decrease in plasma viral load with half of the participants
      decreasing their plasma viral load to below the limit of quantification of the
      assay. This response, however, is seriously compromised by prior exposure to
      protease inhibitors.

PMID- 9583603
TI  - Maximum impact of HIV prevention measures targeted at injecting drug users.
AB  - OBJECTIVE: To examine whether the decrease in HIV incidence and injecting risk
      behaviours is ongoing in Amsterdam, and to study the determinants of injecting
      risk behaviours. DESIGN: Prospective open cohort study (1986-1997) amongst
      injecting drug users (IDU). METHODS: HIV incidence was studied using Poisson
      regression analysis. Trends in injecting risk behaviours were determined using
      6645 visits of 879 participants, stratified by HIV serostatus and number of the
      follow-up visit. Generalized estimating equations were used to account for
      repeated measurements, and additive model structures were used. RESULTS: A large
      initial risk reduction (1986-1991) occurred concerning borrowing and lending of
      used needles, multiple needle use and frequent injecting. However, except for
      frequent injecting, the rate of behaviour change significantly decreased, and
      from 1991-1993 onwards there was no substantial further risk reduction. HIV
      incidence followed a similar pattern. Injecting risk was much lower at follow-up
      visits. The following determinants of borrowing and lending among both HIV
      positive and negative IDU were largely comparable: young age, non-injecting
      heroin and cocaine use, frequent tranquillizer use, multiple needle use,
      injecting with others, and irregular use of needle-exchange programmes.
      CONCLUSIONS: The observed residual risk, given the extensive HIV prevention
      measures in Amsterdam, indicates that further prevention is difficult. Because
      this risk was associated with an HIV incidence of 3-4% per year, HIV prevalence
      is likely to be high for many years. Therefore, prevention measures should be
      maintained because of the possibility of behavioural relapse associated with
      recent availability of potent HIV treatments. To prevent an HIV epidemic amongst
      a new generation of drug users, prevention of injecting itself is warranted.

PMID- 9583604
TI  - HIV-1 strains specific for Dutch injecting drug users in heterosexually infected
      individuals in The Netherlands.
AB  - OBJECTIVE: To study the molecular epidemiology of HIV-1 subtype B amongst
      heterosexually infected individuals in The Netherlands. DESIGN: The study
      population comprised 54 individuals infected by subtype B viruses through
      heterosexual contacts. Serum samples were collected between 1988 and 1996.
      METHODS: Sequences of the gp120 V3 region were obtained from serum samples and
      analysed by using the signature pattern and phylogenetic methods. RESULTS: In 22
      (41%) out of 54 subtype B sequences from heterosexually infected individuals, the
      synonymous nucleotide substitution in the second glycine codon at the tip of the
      V3 loop (the GGC pattern), previously identified as specific for Dutch injecting
      drug users (IDU), was found. The other previously described IDU sequence patterns
      were observed significantly more often among GGC- than among non-GGC-containing
      sequences. In addition, we identified another amino-acid change specific for the
      GGC sequences. In the phylogenetic and principal coordinate analyses, the GGC
      sequences from heterosexually infected individuals clustered separately from the
      non-GGC sequences and together with the IDU consensus sequence. Both the
      nonsynonymous and particularly the synonymous distances amongst the GGC sequences
      were significantly lower than amongst the non-GGC sequences. CONCLUSIONS: Our
      data provide evidence for a common origin of the viruses in Dutch IDU and the GGC
      viruses in heterosexuals. We suggest that a considerable proportion of the
      viruses in heterosexually infected individuals in The Netherlands may have
      originated from Dutch IDU.

PMID- 9583605
TI  - Effect of HIV-1 infection on pregnancy outcome in women in Kigali, Rwanda, 1992
      1994. Pregnancy and HIV Study Group.
AB  - OBJECTIVE: To study the effect of HIV-1 infection on pregnancy outcome in women
      provided with antenatal services including malaria and sexually transmitted
      disease (STD) treatment in Kigali, Rwanda. SUBJECTS AND METHODS: Pregnant women
      attending the antenatal clinic ward of the Centre Hospitalier de Kigali in their
      last 3 months of pregnancy were tested for HIV antibody after consent had been
      obtained. All HIV-1-infected women were included and compared with HIV-negative
      women of same age and parity. Until delivery, each woman enrolled had a monthly
      follow-up including malaria and STD aetiological diagnosis and treatment. At the
      time of delivery, obstetrical and neonatal characteristics were recorded. Mothers
      and their children were followed until 6 weeks postpartum. RESULTS: By mid-August
      1993, 384 HIV-positive and 381 HIV-negative women had been enrolled and by the
      end of November 1993, 729 women (95.3%; 364 HIV-positive and 365 HIV-negative)
      had delivered 725 livebirths, including eight and six twins, respectively; 10
      stillbirths were recorded amongst HIV-positive women and eight amongst HIV
      negative women (P=0.60). Excluding twins, premature birth (< 37 completed weeks
      of gestation) was observed in 22.7% of infants born to HIV-positive women versus
      14.1% of those born to HIV-negative women; low birth weight (< 2500 g) was
      observed in 25.5% of infants born to HIV-positive women versus 14.8% of those
      born to HIV-negative women. Low birth weight was significantly more frequent in
      full-term infants born to HIV-positive mothers than to HIV-negative mothers. No
      significant difference in low birth weight rate was observed in preterm infants.
      Death occurred in 5.1% of children during the perinatal period without
      statistically significant difference between the two groups. HIV-positive women
      were more likely to have a postpartum haemorrhage. CONCLUSION: In the context of
      high HIV prevalence, maternal HIV infection is associated with adverse
      obstetrical and neonatal outcomes even when treating STD and malaria.

PMID- 9583606
TI  - Pre-AIDS mortality in HIV-infected individuals in England, Wales and Northern
      Ireland, 1982-1996.
AB  - OBJECTIVE: To assess pre-AIDS mortality in HIV-infected patients in England,
      Wales and Northern Ireland during the period 1982-1996. DESIGN: Surveillance data
      on pre-AIDS and AIDS deaths reported to the PHLS-AIDS Centre were analysed.
      METHODS: Pre-AIDS mortality was estimated as the proportion of pre-AIDS deaths
      among all deaths in HIV-infected people. Trends over time in the number of pre
      AIDS and AIDS deaths were compared using Poisson regression with logarithmic
      link. Causes of pre-AIDS deaths were recorded. Comparisons were made between the
      pre-AIDS and the AIDS death groups by logistic regression for: age, location of
      residence at death, year of death and risk exposure. RESULTS: Four-hundred and
      sixty-eight pre-AIDS deaths and 8574 AIDS deaths were identified. Pre-AIDS
      mortality accounted for 5.0% of HIV-related deaths. Trends over time in the
      number of pre-AIDS and AIDS deaths were not significantly different (P=0.11).
      Reported causes of pre-AIDS death included pneumonia (92), liver disease (62),
      septicaemia (51), malignancies (49), suicide (45), cardiopulmonary causes (46),
      haemorrhage (42), overdose (24) and accidental causes (24). Factors positively
      associated with pre-AIDS death were injecting drug use, haemophilia and blood
      transfusion, residence outside the Thames regions, and death at an older age.
      CONCLUSIONS: Pre-AIDS mortality represents a substantial proportion of HIV
      mortality, particularly where injecting drug use is a frequent route of HIV
      transmission.

PMID- 9583607
TI  - The AIDS incubation period in the UK estimated from a national register of HIV
      seroconverters. UK Register of HIV Seroconverters Steering Committee.
AB  - OBJECTIVES: To monitor changes in the distribution of time intervals from HIV
      seroconversion to the onset of AIDS and to death and to describe factors
      associated with the length of these intervals, through a national register of
      persons with estimated dates of HIV seroconversion. DESIGN AND METHODS:
      Clinicians caring for HIV-positive individuals and laboratories performing HIV
      testing throughout the UK were asked to identify all persons aged 16 years or
      over with a history of a negative HIV antibody test within 3 years of their first
      positive test, including those who had died, transferred to other centres or who
      had become lost to follow-up. Baseline and follow-up information collected
      annually includes: sex, ethnic group, likely route for HIV transmission, latest
      CD4 count, details of antiretroviral therapy and prophylaxis for opportunistic
      infections, AIDS-defining events and vital status. RESULTS: The analysis in this
      report was censored at 31 December 1994 and includes 961 individuals with
      verified previous negative antibody tests. Within 10 years of seroconversion, we
      estimate the probability of progressing to AIDS to be 60.2% [95% confidence
      intervals (CI), 52.1-68.3] and of death from any cause to be 48.1% (95% CI, 40.1
      56.1%). Older age at seroconversion was found to be associated with faster
      progression to AIDS (P=0.008) as well as shorter survival (P=0.001). No evidence
      of a change in the incubation period nor of a survival benefit was observed by
      calendar time from 1983 to 1994. CONCLUSIONS: Preliminary results from the UK
      Register confirm the strong influence of age on disease progression in line with
      findings from a number of studies. The Register has succeeded in accruing
      information on a large number of seroconverters, and will continue to monitor the
      clinical course of HIV disease, including persons infected in the 1990s. This is
      important as a number of clinical trials have recently reported an improvement in
      survival for persons on multiple drug regimens, the long-term impact of which can
      only be monitored through observational studies.

PMID- 9583608
TI  - Understanding the long-term course of HIV epidemics.

PMID- 9583609
TI  - Subtype-specific polymerase chain reaction for the identification of HIV-1
      genetic subtypes circulating in Africa.

PMID- 9583611
TI  - Enhanced detection of human herpesvirus-8 and cytomegalovirus in semen of HIV
      seropositive asymptomatic heterosexual men living in Central Africa.

PMID- 9583610
TI  - Quantitative techniques and HIV-1 load in plasma and semen.

PMID- 9583612
TI  - Remitting infratentorial leukoencephalopathy in a patient with HIV infection.

PMID- 9583613
TI  - Lack of efficacy of cidofovir in treating AIDS-related cytomegalovirus retinitis
      after long-term treatment with ganciclovir.

PMID- 9583615
TI  - On the issue of cross-resistance between protease inhibitors.

PMID- 9583614
TI  - Discontinuation of Mycobacterium avium complex prophylaxis in patients with a
      rise in CD4 cell count following highly active antiretroviral therapy.

PMID- 9583616
TI  - Gynecomastia during indinavir antiretroviral therapy in HIV infection.

PMID- 9583617
TI  - Steroids as possible inhibitors of HIV-1 protease.

PMID- 9583618
TI  - Adherence to the antiretroviral treatment in asymptomatic HIV-infected patients.

PMID- 9583619
TI  - Smoking in movies: is it a problem?

PMID- 9583621
TI  - 10th World Conference on Tobacco or Health.

PMID- 9583620
TI  - Anti-tobacco floor tiles: a new medium to reach young people.

PMID- 9583622
TI  - Beauty or the beast.

PMID- 9583623
TI  - Philip Morris goes nuts in Brazil.

PMID- 9583624
TI  - US women: smoking defenders, not cigarettes.

PMID- 9583625
TI  - Tobacco use is increasing in popular films.
AB  - OBJECTIVE: To study the presentation of smoking in motion pictures. DESIGN: This
      study examined tobacco use in a random sample of five of the top 20 grossing
      films each year from 1990-1996 and combined these data with our earlier study of
      tobacco use in films that covered 1960-1990. MAIN OUTCOME MEASURES: Rate of
      tobacco use per minute of film, characters who are smoking, motivation to smoke.
      RESULTS: The overall rate of tobacco use appears to have "bottomed out" in the
      1980s and is now increasing back to levels observed in the 1960s. The
      presentation of tobacco use in films is increasingly discordant with reality,
      because tobacco use in the population continues to drop. Films continue to
      portray smokers as successful white males, although portrayal of smoking among
      women is increasing. CONCLUSIONS: The gap between the representation of tobacco
      use in films and the reality of tobacco continues to widen, with the prevalence
      of smoking among lead characters four times the smoking prevalence among
      comparable individuals in society at large.

PMID- 9583626
TI  - Smoking experimentation and initiation among adolescent girls: qualitative and
      quantitative findings.
AB  - OBJECTIVE: To use qualitative and quantitative findings to describe patterns of
      smoking experimentation and initiation among adolescent girls. DESIGN:
      Ethnographic in-person interviews, focus groups, telephone interviews, and a
      survey questionnaire were used over a one-year period. The paper reports on cross
      sectional data drawn from a three-year longitudinal study. SUBJECTS AND SETTING:
      205 girls participated in the survey and interviews during year 3 of the study.
      Girls were drawn from two urban high schools in Tucson, Arizona (USA), and were
      in grades 10 and 11 (mean ages 16 and 17, respectively) during year 3. RESULTS:
      Overall, 30% (n = 61) of informants reported that they currently smoked, 7% (n =
      15) were ex-smokers, and 63% (n = 129) were "non-smokers". The most frequently
      cited reasons for smoking were stress reduction and relaxation. Several stress
      inducing situations, including family environment, social relations with
      classmates, and schoolwork, are discussed. The notion of peer pressure is re
      examined in the light of teenagers' experience that there is little overt
      pressure to initiate smoking. Consonant with notions of adolescent autonomy, the
      theme of independence in smoking initiation and continuation permeated girls'
      narratives about their smoking behaviour. Girls projected the image that they
      could control their cigarettes rather than have their cigarettes control them.
      CONCLUSIONS: Smoking prevention and cessation programmes need to address and
      counter the smoking/relaxation association, which was identified as an important
      reason for smoking among adolescent girls. Questions typically used in surveys to
      measure smoking behaviour do not adequately define the smoking experience as
      described by teenagers.

PMID- 9583627
TI  - Environmental tobacco smoke exposure in the home and worksite and health effects
      in adults: results from the 1991 National Health Interview Survey.
AB  - OBJECTIVE: To determine the effect of environmental tobacco smoke (ETS) exposure
      in the home and worksite on the health of adults in the United States. DESIGN:
      Cross-sectional survey. SETTING: Nationally representative population.
      PARTICIPANTS: 43,732 adults who completed the Health Promotion and Disease
      Prevention supplement in the 1991 National Health Interview Survey. MAIN OUTCOME
      MEASURES: Rate of restricted activity, bed confinement, and work absence in the
      two weeks preceding the survey and self-reported health status among adults with
      and without exposure to ETS. RESULTS: We found that only 20.2% of never-smokers
      and 23.1% of former smokers reported exposure to ETS at home or work, whereas
      87.2% of current smokers reported exposure to ETS. Among never-smokers, after
      adjusting for covariates, people who were exposed to ETS were more likely to
      report one or more days of restricted activity (relative risk (RR) = 1.27, 95%
      confidence interval (CI) = 1.10 to 1.46), one or more days of bed confinement (RR
      = 1.43, 95% CI = 1.19 to 1.73), and one or more days of work absence (RR = 1.33,
      95% CI = 1.05 to 1.73) in the two weeks before the survey than were people
      without such exposure. We detected smaller trends for one or more days of
      restricted activity among current and former smokers (RR = 1.16, 95% CI = 0.97 to
      1.40; and RR = 1.11, 95% CI = 0.82 to 1.51), one or more days of bed confinement
      among current smokers (RR = 1.34, 95% CI = 0.95 to 1.88), and one or more days of
      work absence among former smokers (RR = 1.13, 95% CI = 0.84 to 1.50) in the two
      weeks before the survey than among people without such exposure, although the CIs
      were wide and chance cannot be excluded as an explanation for these findings.
      Never-smokers (RR = 1.47, 95% CI = 1.34 to 1.62), former smokers (RR = 1.22, 95%
      CI = 1.07 to 1.39) and current smokers (RR = 1.31, 95% CI = 1.10 to 1.56) exposed
      to ETS were all more likely to report a less than very good health status than
      were people without such exposure. CONCLUSIONS: This study demonstrates that
      never-smoking adults exposed to ETS report more acute health effects than
      unexposed, never-smoking adults, and suggests similar findings in current and
      former smoking adults.

PMID- 9583628
TI  - Public health benefit of over-the-counter nicotine medications.
AB  - OBJECTIVE: To estimate the impact of allowing non-prescription sales of nicotine
      medications in the United States on increasing the numbers of smokers quitting.
      DESIGN: Sales and marketing data were used to compare the use of nicotine
      medications before and after non-prescription sales, and to estimate the impact
      of non-prescription sales on quit rates. SETTING: United States. MAIN OUTCOME
      MEASURES: Number of quit attempts using nicotine replacement therapy (NRT)
      products, number of smokers who quit smoking with over-the-counter (OTC) NRT or
      with NRT still sold by prescription, and incremental quits attributable to OTC
      NRT. RESULTS: Since the US Food and Drug Administration approved nicotine
      medications for OTC sale in 1996, use of the medications has increased by 152%
      compared with prior prescription use. With increased use of an efficacious
      treatment, OTC nicotine medications are estimated to yield from 114,000-304,000
      new former smokers annually in the United States. CONCLUSIONS: The broader
      availability and promotion of effective treatments for tobacco dependence,
      specifically nicotine gum and patch, increase the number of smokers availing
      themselves of the medications. This increased use is estimated to contribute
      substantially to the number of former smokers in the United States.

PMID- 9583629
TI  - Aiding reduction of smoking with nicotine replacement medications: hope for the
      recalcitrant smoker?
AB  - OBJECTIVE: To assess the effect of the various nicotine replacement therapies
      (NRT) on smoking reduction. DESIGN: During an initial sampling week, the subjects
      familiarised themselves with nicotine gum, patch, nasal spray, vaporiser (vapour
      inhaler) and sublingual tablet. A crossover design was used during the next four
      study weeks; during two of these weeks the subjects could select one nicotine
      replacement product of their choice to use, whereas during the other two they
      were randomly assigned a product to use. SUBJECTS: 143 men and women smoking an
      average of 22.6 (SD 7.0) cigarettes per day and exhibiting a Fagerstrom Tolerance
      Questionnaire (FTQ) score of 7.0 (SD 1.9). INTERVENTIONS: Subjects were asked to
      use as much NRT as they wished, yet to smoke enough to feel comfortable. MAIN
      OUTCOME MEASURES: Self-reported cigarette consumption, exhaled carbon monoxide
      (CO), withdrawal symptom score, cotinine plasma levels and motivation to quit
      were monitored over a period of five weeks. RESULTS: Self-reported smoking
      declined steadily over the five weeks, from 22.6 (SD 7.0) to 10.4 (SD 1.0)
      (P<0.001) cigarettes daily (54% decrease), with the biggest drop (37%) during the
      first product-sampling week. Smoking reduction was greater on average during the
      weeks when the subjects could choose their nicotine product than when products
      were assigned. CO readings decreased from 22.7 (SD 8.5) to 14.8 (SD 8.4) ppm
      (P<0.001) confirming a reduction in smoking (35% decrease), although cotinine
      levels remained steady, suggesting that subjects were titrating nicotine to their
      original levels. Withdrawal scores decreased over time (32% decrease, P<0.001),
      showing that there was no discomfort associated with the smoking reduction, and
      motivation to quit was enhanced by the treatment in most subjects (93%).
      CONCLUSIONS: NRT for aiding smoking reduction appeared to be safe, was associated
      with a clinically significant reduction in smoke exposure over a five-week follow
      up, and increased motivation to stop smoking. A smoking reduction procedure may
      help the very recalcitrant smoker gain confidence and increase the control over
      his/her smoking behaviour. More controlled research is needed to follow up these
      promising results.

PMID- 9583630
TI  - Initial impact of the new Australian tobacco health warnings on knowledge and
      beliefs.
AB  - BACKGROUND: New health warnings and contents labelling on tobacco products were
      introduced in Australia in 1995. OBJECTIVE: To assess awareness of the new
      warnings at a time when a mix of packs with old and new warnings were being sold
      and on changes in relevant knowledge and attitudes from shortly before the
      implementation of the new warnings. DESIGN AND SUBJECTS: Approximately 500
      smokers and 500 non-smokers were surveyed in December 1994, before implementation
      of the new warnings. Similar numbers were also surveyed in May 1995, part-way
      through implementation. Respondents were selected by random-digit dialling of
      telephone numbers in Australia. Smokers were oversampled. In addition, 243
      smokers from the initial survey were re-surveyed in May 1995. MAIN OUTCOME
      MEASURES: Awareness of change to health warnings, knowledge of health warnings
      and tobacco smoke constituents, beliefs about the health effects of smoking, and
      perceived impact of the warnings. RESULTS: There was high awareness of the new
      warnings, particularly among smokers, with the increased size of the new warnings
      being the most salient feature. More than a third of smokers reported being
      affected by the warnings, with reductions in consumption and talking about
      warnings being the most common effects. Among smokers, there was an increase in
      knowledge about the main constituents of tobacco smoke. The number of types of
      health effects mentioned also increased as did the number of warnings correctly
      recalled. Overall beliefs about the six warning statements became stronger. Few
      changes were found for non-smokers. The knowledge and recall effects were
      replicated in the re-contact subsample, but the belief changes were not.
      CONCLUSIONS: These results suggest the new health warnings are resulting in
      better informed smokers and thus suggest that informative health warnings can
      play an important role in better informing consumers.

PMID- 9583631
TI  - Evaluating compliance with Australia's first smoke-free public places
      legislation.
AB  - OBJECTIVE: To measure the level of compliance among businesses with legislation
      prohibiting smoking in public places. DESIGN: A representative sample of
      businesses in the Australian Capital Territory (ACT) was selected. A two-phase
      survey design was used: in phase 1, interviewers observed business premises to
      evaluate their compliance with the legislation, observing the display of no
      smoking signs and noting any evidence of smoking in smoking-prohibited areas; in
      phase 2, a short questionnaire was completed by the business owner or manager.
      SETTING: Observations of business premises and self-completion interviews with
      owners or managers of those premises. SUBJECTS: 938 respondents who were either
      owners, managers, or employees of ACT businesses. MAIN OUTCOME MEASURES:
      Compliance with legislation prohibiting smoking in the public areas of business
      premises; businesses' own perceptions of the extent of their compliance; and the
      factors affecting the discrepancy between actual and perceived compliance.
      RESULTS: A total of 22% of the businesses complied fully with the legislation,
      whereas 56% partially complied by displaying external or internal signage. Most
      respondents (84%) believed that they were complying fully with the legislation.
      Only 21% of the businesses complied and correctly assessed their compliance.
      Evidence of smoking was detected in only 5% of no-smoking premises. The type of
      business and the smoking policy of the establishment at the time the legislation
      came into force were important influences on compliance, followed by whether the
      premises were free-standing or located within shopping malls. The mass media was
      identified as the main source of information about the legislation. CONCLUSIONS:
      Ensuring the successful implementation of non-smoking legislation is facilitated
      by (a) widespread publicity to make business proprietors and their customers and
      clients aware of the legislation; (b) first implementing legislation in premises
      where there is strong public support for such measures; and (c) targeting
      information to premises that have pre-existing policies prohibiting smoking on
      their premises.

PMID- 9583632
TI  - State legislators' perceptions of lobbyists and lobbying on tobacco control
      issues.
AB  - OBJECTIVE: To determine state legislators' perceptions about health and tobacco
      lobbyists, their frequency of contact with these lobbyists, and the amount of
      campaign contributions from health professional organisations and the tobacco
      industry. DESIGN: Cross-sectional study. SUBJECTS: State legislators from North
      Carolina, Texas, and Vermont (USA), serving in 1994. MAIN OUTCOME MEASURES:
      Perceptions about lobbyists representing the tobacco industry, non-profit health
      organisations, and state medical societies with respect to their credibility,
      importance as sources of information, and persuasiveness; extent of lobbying
      activities; campaign contributions from health professional organisations and the
      tobacco industry. RESULTS: Almost all legislators reported that medical society
      and non-profit health organisation lobbyists are credible on tobacco issues and
      just over half believed that these lobbyists are important sources of
      information. More legislators said they could be persuaded by medical and health
      lobbyists than by tobacco lobbyists. Although health professional Political
      Action Committees (PACs) gave campaign contributions to more state legislators,
      and gave higher amounts on average, than tobacco PACs, legislators reported less
      contact with medical society lobbyists than tobacco lobbyists about tobacco
      issues. CONCLUSIONS: State legislators have positive attitudes toward lobbyists
      for non-profit health organisations and state medical societies regarding tobacco
      issues. These groups may be an underused resource for educating legislators about
      tobacco control measures.

PMID- 9583634
TI  - When SCIENCE doesn't make sense.

PMID- 9583633
TI  - After ASSIST, what next? SCIENCE.

PMID- 9583635
TI  - Building on the foundation of ASSIST.

PMID- 9583636
TI  - The future of NCI's smoking research agenda.

PMID- 9583637
TI  - Tobacco control in the United States: the next generation of demonstration and
      research projects.

PMID- 9583638
TI  - In support of SCIENCE.

PMID- 9583639
TI  - Health effects of exposure to environmental tobacco smoke. California
      Environmental Protection Agency.

PMID- 9583640
TI  - Nothing is sacred on the Philippine smoking front.

PMID- 9583641
TI  - Fuel pump promos.

PMID- 9583642
TI  - Children and tobacco, Information Sourcepage, 10th WCTOH, WHO, a Diary of Denial,
      investing in tobacco, plus a gallery of cigarette packs. World Conference on
      Tobacco or Health.

PMID- 9583643
TI  - Against a tangled web.

PMID- 9583644
TI  - Evolution of tobacco control studies at the National Cancer Institute.

PMID- 9583645
TI  - From tobacco mythology to science: will policy research ever guide practice?

PMID- 9583646
TI  - The American Stop Smoking Intervention Study for cancer prevention: an overview.
AB  - The American Stop Smoking Intervention Study (ASSIST) is a programme to implement
      proven interventions in 17 states across the United States. ASSIST applies all
      that we have learned in 10 years of research on tobacco use prevention and
      control. The goal of this seven-year project is to reduce the prevalence of
      smoking and cigarette consumption in the ASSIST states. The scientific basis for
      ASSIST is described, followed by a general description of the project and its
      current status in the 17 targeted states.

PMID- 9583647
TI  - Impact of the American Stop Smoking Intervention Study on cigarette consumption.
AB  - OBJECTIVE: To obtain an early estimate of the effectiveness of the American Stop
      Smoking Intervention Study (ASSIST). DESIGN, SETTING, AND PARTICIPANTS: Seventeen
      American states funded through ASSIST are compared with 32 others regarding per
      capita cigarette consumption from 1989 to 1995. California, which already had an
      extensive tobacco control programme, was omitted. ASSIST states were selected
      competitively (not randomly) based on their proposals' merit, state smoking
      prevalence, and geographical distribution. INTERVENTIONS: Comprehensive tobacco
      control programmes, emphasising policy interventions, were implemented in the
      ASSIST states beginning in 1993. MAIN OUTCOME MEASURES: Trends in aggregated per
      capita cigarette consumption and inflation-adjusted average price/pack of
      cigarettes in the intervention states were compared. Percentage change in per
      capita consumption is also compared with percentage change in inflation-adjusted
      cigarette price by state in each group from 1992 to 1994. RESULTS: Per capita
      consumption and inflation-adjusted cigarette price were nearly identical in both
      groups of states before 1993, when full funding for the ASSIST interventions
      began. However, by 1996 smokers in the intervention states were consuming about
      7% less cigarettes per capita (P<0.05, beginning in 1994), and in 1994 the
      average price was over $0.12/pack higher in the intervention states. All but
      three states (all intervention) showed decreases in cigarette price. Nonetheless,
      76% of the intervention and 55% of the comparison states showed some decrease in
      consumption despite decreases in price. The relationship between changes in price
      and consumption was considerably diminished in the intervention group.
      CONCLUSIONS: These interim results suggest that the ASSIST programme is
      associated with a substantial difference in tobacco consumption in a third of the
      United States, and that increased price from taxation may not be the only
      programme influence.

PMID- 9583648
TI  - Price, public policy, and smoking in young people.
AB  - OBJECTIVE: To examine the effect of cigarette taxes, limits on public smoking,
      laws regulating access to tobacco by young people, and exposure to pro-tobacco
      and anti-tobacco messages on smoking participation and the intention to smoke
      among ninth-grade students (aged 13-16). DATA SOURCES: Two cross-sectional,
      school-based surveys (total of 15432 responses) of ninth-grade students conducted
      in 21 North American communities in 1990 and 1992 in conjunction with the
      Community Intervention Trial for Smoking Cessation. OUTCOME MEASURES: A ninth
      grader was classified as a smoker if he or she reported smoking a whole cigarette
      on at least one of the 30 days preceding the survey. Among non-smokers, a
      positive intention to smoke was attributed to those who claimed they probably or
      definitely would be smoking within a year. RESULTS: Both smoking participation
      and the intent to smoke were related to differences in cigarette prices, with
      estimated price elasticities of -0.87 and -0.95, respectively. Boys were far more
      sensitive to price than girls with respect to smoking participation (elasticities
      of -1.51 and -0.32, respectively); however, the effect of price on the intent to
      smoke was similar for boys and girls. Policies limiting minors' access to tobacco
      (a minimum purchase age of 18 years, a ban on cigarette vending machines, and a
      ban on giving away free samples of tobacco products) were associated with
      reductions in participation and intention to smoke. Exposure to tobacco education
      in school was associated with decreased participation and intention to smoke.
      Policies that prohibited smoking in public places and in schools were not
      significantly related to the smoking patterns of ninth-graders. Frequency of
      exposure to pro-tobacco advertisements was marginally associated with increased
      participation and intention to smoke; paradoxically, frequency of exposure to
      anti-tobacco advertisements was correlated with an increased likelihood of
      smoking. CONCLUSIONS: Policies limiting access to tobacco by young people,
      increasing education about the effects of tobacco use, and a sharp and sustained
      increase in real cigarette excise taxes are likely to be most successful in
      accomplishing the US Food and Drug Administration's goal of cutting the smoking
      prevalence of adolescents in half over the next seven years.

PMID- 9583649
TI  - Use of discount cigarettes by smokers in 20 communities in the United States,
      1988-1993.
AB  - OBJECTIVE: To examine characteristics of smokers associated with the use of
      discount and generic cigarettes. DESIGN: Data for this analysis come from two
      population-based cross-sectional telephone surveys (1988 survey n = 32952; 1993
      survey n = 11783) and a cohort tracking survey (n = 11966) of smokers aged 25-64
      years conducted in 20 communities in the United States between 1988 and 1993 as
      part of the National Cancer Institute's Community Intervention Trial for Smoking
      Cessation. OUTCOME MEASURES: In each survey, current smokers were asked to report
      the six-digit UPC code displayed on the side of the pack of their current
      cigarettes. Respondents who did not have a pack available or who could not locate
      the UPC code number were asked to report their usual brand of cigarettes smoked.
      A master list of UPC code numbers was developed so that reported UPC codes could
      be associated with specific cigarette brand names. Brand name cigarettes were
      categorised as either premium or discount brands using information from the
      Maxwell consumer report. Respondents who reported smoking "no name" generic
      cigarettes were classified as smoking a discount cigarette. RESULTS: The reported
      use of discount/generic cigarettes increased from 6.2% in 1988 to 23.4% in 1993.
      The trend toward increased use of lower priced cigarettes was evident in all 20
      communities studied. The use of low priced cigarettes was associated with lower
      household income, higher daily cigarette consumption, and residence in an area
      with higher average cigarette prices. Respondents using discount/generic
      cigarettes were less likely to stop smoking or to reduce cigarette consumption
      between 1988 and 1993 compared with those using premium brand cigarettes.
      CONCLUSIONS: The availability of discount/generic cigarettes has made smoking
      more affordable, which most likely has helped the cigarette industry retain
      customers sensitive to price, who might have otherwise reduced consumption or
      stop smoking altogether.

PMID- 9583650
TI  - Comparison of recent trends in adolescent and adult cigarette smoking behaviour
      and brand preferences.
AB  - OBJECTIVE: To compare trends in smoking behaviour and use of cigarette brands by
      adults and adolescents. DESIGN: Data analysed in this paper come from tobacco use
      surveys of adults and teenagers conducted in 18 communities in the United States,
      as part of the National Cancer Institute's Community Intervention Trial for
      Smoking Cessation. Data on adult smoking behaviour were obtained from two cross
      sectional telephone surveys, one conducted from January to May 1988 (n = 99348),
      and the second conducted between August 1993 and January 1994 (n = 79890). Data
      on adolescent smoking behaviour were obtained from two school-based surveys of
      ninth-grade students (aged 13-16 years), one conducted in autumn 1990 (n = 7097),
      and the second conducted in autumn 1992 (n = 7277). OUTCOME MEASURES: Adult
      cigarette smoking prevalence was estimated as the percentage of adults (18+
      years) who were identified either by interview or by proxy as a current smoker.
      Among adolescents, current smokers were defined as those who reported having
      smoked on one or more of the 30 days preceding the interview. Cigarette brand use
      by adults was measured by asking current smokers to report the six digit UPC code
      on the side of the pack of their current cigarettes. A master list of UPC code
      numbers was developed so that reported codes could be associated with specific
      brand names. Among adolescents, cigarette brand use was measured by asking
      current smokers who reported that they usually buy their own cigarettes: "What
      brand do you usually buy?" RESULTS: In ninth-grade students, smoking prevalence
      rates increased between 1990 and 1992 in 13 of the 18 communities. Among adults,
      smoking rates declined between 1988 and 1993 in 17 out of 18 communities. Within
      the same communities, cigarette brand use was found to be much more tightly
      concentrated in adolescent smokers compared with adults, with teenage smokers
      more likely to report using the most heavily advertised cigarette brands-
      Marlboro, Newport, and Camel. CONCLUSIONS: Smoking prevalence rates have
      increased among teenagers, but have dropped among adults in the same communities.
      Among adolescents who smoke, and buy their own cigarettes, the three most heavily
      advertised brands--Marlboro, Camel, and Newport--have a substantially higher
      market concentration than among adult smokers.

PMID- 9583651
TI  - Discrepancies in cigarette brand sales and adult market share: are new teen
      smokers filling the gap?
AB  - OBJECTIVE: To examine the extent and type of cigarette brand switching by adult
      smokers. To evaluate discrepancies between actual and projected cigarette brand
      sales based on changes in adult smoking patterns. DESIGN: Data analysed come from
      a cohort tracking survey of 11966 cigarette smokers aged 25-64 years from 20
      communities in the United States who were followed between 1988 and 1993 as part
      of the National Cancer Institute's Community Intervention Trial for Smoking
      Cessation. OUTCOME MEASURES: Respondents were asked about their current cigarette
      brand in 1988 and 1993. Brand switching was inferred when a smoker reported a
      different cigarette brand in 1988 and 1993. Company switching was defined as
      brand switching for whom a different parent company was identified for the 1993
      brand compared with the brand used in 1988. A ratio measure was computed to
      reflect gains in market share from brand switching and losses from brand
      switching, quitting, and death, for specific cigarette brands, between 1988 and
      1993. This ratio measure was used to estimate the projected unit sales for top
      selling premium brands in 1993 and was compared with actual unit sales for the
      same year. RESULTS: We estimate that an average of 9.5% of smokers switched
      cigarettes brands and 7.6% switched companies each year. Most of those who did
      switch cigarette brands changed from a premium brand to a discount or generic
      brand. Between 1988 and 1993, top-selling premium brands such as Marlboro, Camel,
      and Newport, lost about four times as many adult smokers as they gained. Whereas
      premium brand cigarettes lost some smokers to discount and generic cigarettes,
      over 50% of losses were due to smokers quitting or dying. Actual unit sales were
      substantially higher than projected sales (based on adult market share) for
      Marlboro and Camel, but not for other brands. CONCLUSIONS: Most smokers are brand
      loyal. Price seems to be an important factor motivating brand switching among
      adult smokers. It appears that recruitment of new customers among the ranks of
      non-smokers is necessary for premium cigarette brands such as Marlboro and Camel
      to maintain sales comparable to previous years.

PMID- 9583652
TI  - Relationship of worksite smoking policy to changes in employee tobacco use:
      findings from COMMIT. Community Intervention Trial for Smoking Cessation.
AB  - OBJECTIVE: To report data on the impact of worksite smoking policies on employee
      smoking behaviour from a large and heterogeneous sample of smokers and worksites
      in 22 different communities across North America participating in the COMMIT
      trial. DESIGN AND SUBJECTS: Data from a population-based survey of 8271 employed
      adult smokers who completed surveys in 1988 and 1993. Surveys included questions
      on tobacco use behaviours, personal/demographic characteristics, and smoking
      policy and cessation resources at the workplace. RESULTS: After controlling for
      potential confounding factors, regression analyses revealed that employees who
      worked in a smoke-free worksite were over 25% more likely to make a serious quit
      attempt between 1988 and 1993, and over 25% more likely to achieve cessation than
      those who worked in a worksite that permitted smoking. Among continuing smokers,
      employees in smoke-free worksites consumed an average of 2 3/4 fewer cigarettes
      per day compared with those who worked in places with a non-restrictive smoking
      policy. A smoke-free worksite policy was not associated with a greater likelihood
      of using smokeless tobacco. CONCLUSION: These data, from one of the largest and
      longest smoking cessation studies to date, add support to the conclusion that
      smoke-free worksite policies help employees to reduce or discontinue use of
      tobacco.

PMID- 9583653
TI  - Tobacco control activities of primary-care physicians in the Community
      Intervention Trial for Smoking Cessation. COMMIT Research Group.
AB  - OBJECTIVE: To compare tobacco control practices of physicians and their staff in
      Intervention communities with those in Comparison communities of the Community
      Intervention Trial for Smoking Cessation (COMMIT). DESIGN: COMMIT was a
      randomised trial testing community-based intervention for smoking cessation
      carried out over four years. SETTING: Eleven matched pairs of communities
      assigned randomly to Intervention and Comparison conditions. PARTICIPANTS AND
      INTERVENTIONS: Physicians in the Intervention communities participated in
      continuing medical education (CME). Training for office staff focused on tobacco
      control and office intervention "systems". OUTCOME MEASURES: Smoking control
      attitudes and practices reported by primary-care physicians in the 22
      communities, smoking policies, and practices of 30 randomly selected medical
      offices in each community, and patient reports of physician intervention
      activities. RESULTS: Response rates to the physicians' mail survey were 45% and
      42% in Intervention and Comparison communities, respectively. Telephone
      interviews of office staff had response rates of 84% in both conditions.
      Physicians in Intervention communities were more likely to attend training than
      those in Comparison communities (53% and 26%, respectively (P<0.0005)). In both
      conditions, training attendees perceived themselves as being better prepared to
      counsel smokers than non-attendees (P < or = 0.01) and reported more activity in
      smoking intervention. Intervention communities carried out more office-based
      tobacco control activities (P = 0.002). Smokers in Intervention communities were
      more likely to report receiving reading material about smoking from their
      physicians (P = 0.026). No other differences in physician intervention activities
      were reported by smokers between the Intervention and Comparison communities.
      CONCLUSIONS: The COMMIT intervention had a significant effect on some reported
      physician behaviours, office practices, and policies. However, most physicians
      still did not use state-of-the-art smoking intervention practices with their
      patients and there was little, or no, difference between patient reports of
      intervention activities of physicians in the Intervention and Comparison
      communities. Better systems and incentives are needed to attract physicians and
      their staff to CME and to encourage them to follow through on what they learn.
      The recently released Agency for Health Care Policy and Research clinical
      practice guideline for smoking cessation and other standards and policies outline
      these systems and offer suggestions for incentives to facilitate adoption of
      these practices by physicians.

PMID- 9583654
TI  - Predictors of smoking cessation in a cohort of adult smokers followed for five
      years.
AB  - OBJECTIVE: To identify variables predictive of smoking cessation in a cohort of
      cigarette smokers followed for five years. DESIGN: Data analysed in this paper
      come from a cohort tracking telephone survey of 13415 cigarette smokers aged 25
      64 years from 20 American and two Canadian communities who were interviewed in
      1988 and re-interviewed in 1993 as part of the National Cancer Institute's
      Community Intervention Trial for Smoking Cessation. Predictors of smoking
      cessation evaluated in this study included measures of past and current smoking
      behaviour, past quit attempts, stated desire to quit smoking, and demographic
      characteristics. OUTCOME MEASURES: Smoking cessation was based on self report. A
      "quitter" was defined as a cohort member who, at the final annual contact in
      1993, reported not smoking any cigarettes for the preceding six months or longer.
      Any smoker who reported having made a serious quit attempt between 1988 and 1993
      was asked to indicate reasons that contributed to their decision to try to stop
      smoking. RESULTS: 67% of smokers reported making at least one serious attempt to
      stop smoking between 1988 and 1993 and, of these, 33% were classified as having
      quit smoking in 1993. The most common reasons given for quitting smoking were
      concern over health (91%), expense (60%), concern about exposing others to
      secondhand smoke (56%), and wanting to set a good example for others (55%).
      Statistically significant predictors of smoking cessation included male gender,
      older age, higher income, less frequent alcohol intake, lower levels of daily
      cigarette consumption, longer time to first cigarette in the morning, the use of
      premium cigarettes, initiation of smoking after age 20, history of past quit
      attempts, a strong desire to stop smoking, and the absence of other smokers in
      the household. Predictor variations with the largest relative risks for smoking
      cessation were those associated with nicotine dependence such as amount smoked
      daily and time to first cigarette in the morning. CONCLUSIONS: Despite the fact
      that most smokers expressed a strong desire to stop smoking in 1988, the
      majority, especially the most dependent heavy smokers (>25 cigarettes/day),
      struggled unsuccessfully to achieve this goal.

PMID- 9583655
TI  - Use of the nicotine skin patch by smokers in 20 communities in the United States,
      1992-1993.
AB  - OBJECTIVE: To measure the characteristics of smokers associated with the use of
      the nicotine skin patch in the general population and to evaluate whether use of
      the patch is associated with successful smoking cessation. DESIGN: Data from two
      surveys conducted in 20 communities in the United States as part of the National
      Cancer Institute's Community Intervention Trial for Smoking Cessation (COMMIT)
      study. Nicotine patch prevalence was estimated using data from a 1993 cross
      sectional survey of 13691 current and former smokers. The effectiveness of the
      nicotine skin patch as a smoking cessation aid was evaluated adjusting for other
      covariants using data from a cohort tracking study of 9809 smokers who were
      followed between 1988 and 1993. As the nicotine patch was not available to
      consumers until January 1992, analyses were restricted to respondents who
      reported themselves to be current smokers in 1993 or former smokers who reported
      quitting after January 1992. OUTCOME MEASURES: Current and former smokers who
      reported having made a serious effort to stop smoking in the past five years were
      asked to indicate whether they had used the nicotine skin patch to help them stop
      smoking. Those answering "Yes", were classified as nicotine patch users. Smoking
      cessation was based on self-report. A "quitter" was defined as someone who had
      been a smoker as of January 1992 who reported in 1993 not smoking any cigarettes
      for the preceding six months or longer. RESULTS: The prevalence of nicotine patch
      use by smokers averaged across the 20 study communities was 12.8%, making the
      patch one of the most popular cessation methods used by smokers. Compared with
      non-users, patch users were more likely to be female, white, have higher annual
      household incomes, be more motivated to stop smoking, and to smoke more heavily.
      Among low-income smokers (annual household income below US$10000), nicotine patch
      use was significantly higher among those who lived in a state where the public
      insurance programme (Medicaid or Medi-Cal) included the patch as a benefit (12.1%
      vs 7.7%). Among those who made an attempt to quit smoking, the likelihood of
      successful quitting was more than twice as high among patch users compared with
      non-users. Among patch users, the highest quit rates were observed among those
      who used the patch for between one and three months. CONCLUSIONS: The nicotine
      skin patch is a popular and effective means of smoking cessation. Use of the
      nicotine patch, especially by low-income smokers, could be increased by reducing
      the out-of-pocket expenditure required for smokers to get the product.

PMID- 9583657
TI  - Family context variables and the development of self-regulation in college
      students.
AB  - While researchers have begun to specify how features of students' immediate
      learning environments affect the development and use of self-regulation skills,
      relatively little attention has been paid to the role of the family context in
      fostering or impeding the development of these skills. This paper proposes a
      conceptual framework based on attachment theory (Ainsworth et al., 1978; Bowlby,
      1982) and Baumrind's parenting styles typology (Baumrind, 1967, 1991) for
      examining the relationship between family context variables and the development
      of self-regulation skills. It also presents initial findings from a study of the
      parental practices and values associated with academic self-regulation in college
      students. A sample of 465 students completed the 104-item Student Attitudes and
      Perceptions Survey, which consists of 4 personal profile scales, 7 family
      background scales, 2 course characteristics scales, and 2 study habits scales.
      Perceptions of parents as authoritative and of family as emotionally close were
      found to be predictive of (1) general confidence and positive sense of self, (2)
      positive goal-orientation at school, (3) general concern about preparation for
      the future, and (4) positive adjustment to college. These family profiles were
      also predictive of (1) students' rating their introductory psychology course as
      interesting and supportive, (2) favorable ratings of their time and effort
      management and note-taking skills, and (3) strong agreement with a series of
      items reflecting components of self-regulated learning. Perceptions of parents as
      authoritarian and of family as nagging or enmeshed were also predictive of
      concern about preparation for the future. These family profiles were generally
      predictive of students' rating their introductory psychology course as difficult,
      and of time and effort management difficulties. The patterns linking family
      background profiles with course perceptions, study habits, and individual indices
      of self-regulated learning persisted even when students' sense of confidence was
      factored out, and were strong for students living with their parents as well as
      for those living on their own.

PMID- 9583656
TI  - Mental health care in a high school based health service.
AB  - This paper describes the mental health services provided at a high school based
      health center that integrates mental health and medical services. Five years
      after the inception of the center in 1988, mental health visits had quadrupled.
      In 1992 alone, students made 1,002 mental health visits. Strikingly, one-third of
      these students reported problematic substance use among other family members.
      Other leading reasons for utilizing mental health services included pregnancy
      (19%), past or present suicidal ideation (14%), obesity (8.7%), ongoing
      depression (8%), and issues related to sexuality (7.5%).

PMID- 9583658
TI  - The birds and the bees: an analysis of advice given to parents through the
      popular press.
AB  - There is a growing need for parents to communicate with their adolescents about
      sexuality, as teenage pregnancies and sexually transmitted diseases are on the
      rise. Many parents indicate that they lack information and feel uncomfortable
      communicating with their children about sex. The popular press regularly
      publishes articles on parenting issues, including how to discuss sex. In this
      study, 26 articles from 1984 to 1993 were reviewed, and the tone, quality of
      information, and advice given to parents on how to communicate were analyzed. The
      articles reflected current research regarding parent-child sexual communication
      and provided much more detailed advice about how best to approach the topic with
      an adolescent. However, readership seemed to be primarily white and mothers in
      traditional families, and little advice was offered on how to handle more
      difficult issues, such as contraception and AIDS. The findings suggest that the
      popular press could serve as an informational vehicle for educating both youth
      and parents about sexuality and how to have productive discussions regarding this
      issue.

PMID- 9583659
TI  - Image advertisements for alcohol products: is their appeal associated with
      adolescents' intention to consume alcohol?
AB  - Criticism has been directed toward alcohol advertising, particularly regarding
      the use of image (lifestyle) advertising, and its potential influence on teenage
      alcohol consumption. This study sought to determine if adolescents who drink, or
      intend to drink alcohol at some future time, find image advertisements for
      alcohol more appealing than product advertisements. The results indicated that
      image advertising was preferred to product advertising, particularly by younger
      adolescents. Evidence of an association between preference for image
      advertisements and intent to drink in the future was found. Policy implications
      of the findings are discussed.

PMID- 9583660
TI  - Removing the mystery: evaluation of a parent manual by adolescent parents.
AB  - The purposes of this study were to (1) have adolescents evaluate a parent manual
      that had been developed specifically for parents of children from birth to age 3,
      and (2) modify the manual based upon the results of the evaluation. The manual
      was designed to be easily read and understood by parents with low education
      levels, the focus being to promote quality parent-child interactions. The study
      was designed to determine the usability of the manual by gathering information
      pertaining to format, readability, and content. Participants were between 14 and
      18 years of age and were enrolled in a high school program for teenage mothers.
      Both written and verbal responses were collected and a qualitative approach was
      used to analyze the data. Results showed that overall comments about the manual
      were favorable; the manual was readable and usable by adolescent mothers of young
      children. However, responses indicated that the manual may not have been as
      relevant for adolescents expecting their first child. They suggested including
      more basic child-care information instead of primarily focusing on typical
      development and parent-child interactions. Participant recommendations were
      considered and the manual was revised.

PMID- 9583661
TI  - The relationship of individual and family factors to the psychological well-being
      of junior high school students living in urban poverty.
AB  - This study examined the contribution of individual and family factors to
      psychological adjustment in a sample of junior high school students living in
      urban poverty. Identity development and perceived parental treatment were
      hypothesized to serve as mediating, or protective, factors between economic
      hardship and levels of self-esteem, depression, and loneliness. Consistent with
      the hypotheses, identity development did serve as a mediator between poverty and
      psychological adjustment. While perceived parental treatment was not related to
      economic hardship, it was clearly associated with well-being in this sample.
      Findings are discussed in terms of the differing contributions of family and
      individual development, as well as the importance of mediators in assessing the
      effects of poverty on young adolescents.

PMID- 9583662
TI  - Effectiveness of one-year participation in school-based volunteer-facilitated
      peer support groups.
AB  - This study evaluated the effectiveness of one-year participation in a program of
      volunteer-facilitated peer support groups conducted in a southeast Texas high
      school. One hundred eighteen students who experienced emotional distress or
      behavioral problems voluntarily participated in weekly groups facilitated by
      adult volunteers who were not mental health professionals. Seventy-six
      participants anonymously assessed the program using an instrument developed to
      evaluate the group experience. Results indicated that the program was highly
      accepted by the students even though two-thirds had initially felt uncomfortable
      in the groups. There was significant improvement in the interpersonal, internal,
      and school domains. Two-thirds of the alcohol and substance users reported
      reducing their intake or abstaining. The beneficial effects reported by a
      majority of the participants indicate that schools opting to implement this early
      intervention program can look forward to encouraging results within one year.

PMID- 9583663
TI  - The effects of two types of relaxation training on students' levels of anxiety.
AB  - In the present study, high school students who received training in either
      behavioral relaxation or progressive muscle relaxation demonstrated significantly
      lower state anxiety scores than did those who had not received such training. No
      significant differences were found on trait anxiety scores. There was no
      significant effect of gender and also no significant interaction effects between
      the three groups and gender for either state or trait anxiety. Implications of
      these findings for high school counselors who work with students dealing with
      anxiety-producing problems are presented.

PMID- 9583664
TI  - Adolescents with attention deficit hyperactivity disorder benefit from massage
      therapy.
AB  - Twenty-eight adolescents with attention deficit hyperactivity disorder were
      provided either massage therapy or relaxation therapy for 10 consecutive school
      days. The massage therapy group, but not the relaxation therapy group, rated
      themselves as happier and observers rated them as fidgeting less following the
      sessions. After the 2-week period, their teachers reported more time on task and
      assigned them lower hyperactivity scores based on classroom behavior.

PMID- 9583665
TI  - Music shifts frontal EEG in depressed adolescents.
AB  - Recent studies have found that positive affect is associated with greater
      relative left frontal EEG activation and negative affect is associated with
      greater relative right frontal EEG activation. Further, chronically depressed
      adults typically display stable right frontal EEG activation. The present study
      investigated the effects of music on mood state and right frontal EEG activation
      associated with chronic depression. Fourteen chronically depressed female
      adolescents listened to rock music for a 23-minute session. These adolescents
      were compared with a control sample of chronically depressed female adolescents
      who were simply asked to sit and relax their minds and their muscles for the same
      time period. EEG was recorded during baseline, music, and postmusic for three
      minutes each, and saliva samples were collected before and after the session to
      determine the effects of the music on stress hormone (cortisol) levels. No group
      differences or changes were noted for observed or reported mood state. However,
      cortisol levels decreased and relative right frontal activation was significantly
      attenuated during and after the music procedure. It was concluded that music had
      positive effects on the physiological and biochemical measures even though
      observed and self-reported mood did not change.

PMID- 9583666
TI  - Polydrug-using adolescent mothers and their infants receiving early intervention.
AB  - This study investigated the effects of an intervention for polydrug-using
      adolescent mothers. The program included educational, vocational, and parenting
      classes; social and drug rehab; and day care for their infants while they
      attended school half-day. The drug-exposed infants were similar to the nonexposed
      infants on traditional birth measures, although they had inferior Brazelton
      Neonatal Behavioral Assessment Scale scores, including habituation, orientation,
      abnormal reflexes, general irritability, and regulatory capacity. The drug
      exposed infants also spent less time in quiet sleep and more time crying and
      showing stress behaviors. Both the mothers and the infants in the drug groups
      demonstrated inferior interactions, and their dopamine and serotonin levels were
      significantly higher. As early as 3 months (following 3 months of intervention),
      the drug rehab mothers and their infants looked more like the nondrug group in
      their interactions; by 6 months, they looked similar on virtually every measure.
      At 12 months, the infants of drug rehab mothers (versus the drug control group)
      had superior Early Social Communication Scale scores and Bayley Mental scale
      scores, as well as significantly greater head circumference and fewer pediatric
      complications. The drug rehab mothers also improved on several lifestyle
      variables. They demonstrated a lower incidence of continued drug use and repeat
      pregnancy, and a greater number continued school, received a high school or
      general equivalency diploma, or were placed in a job. Thus, a relatively cost
      effective high school based intervention had positive effects on both adolescent
      mothers who had used drugs and their infants.

PMID- 9583667
TI  - Mentoring high-risk minority youth: evaluation of the Brothers project.
AB  - Mentoring as an intervention for at-risk teens is becoming increasingly popular
      despite sparse evidence of its effectiveness. This research, part of a larger
      evaluation effort, reports on a four-year mentoring project developed
      specifically for African-American adolescents. Self-esteem, attitudes toward
      drugs and alcohol, grades, school attendance, and disciplinary infractions were
      examined using an experimental design. No significant differences were found
      between the control and intervention groups. However, multiple explanations are
      offered to account for why it is so difficult to document the positive benefits
      of mentoring.

PMID- 9583668
TI  - Scouting and Girl Scout curriculum as interventions: effects on adolescents' self
      esteem.
AB  - This study examined participation in Girl Scouts and use of scouting curriculum
      as interventions for increasing the self-esteem of female adolescents. There were
      no significant pre/post differences among comparison groups. However, Girl Scouts
      had higher self-esteem than did girls without scouting experience and there were
      statistically significant differences in self-esteem by age group. Self-esteem
      decreased with age as measured by both the Rosenberg Self-Esteem Scale and the
      Index of Self-Esteem.

PMID- 9583669
TI  - Drug use among Asian-Indian adolescents: identifying protective/risk factors.
AB  - The problem of meeting the normative demands of two cultures (host country and
      country of origin) has been linked to adolescent substance use as a way to cope
      with conflicts with parents. This paper examines intergenerational conflict as a
      precursor to alcohol, tobacco, and other drug use among second-generation Asian
      Indian adolescents (Asian Americans whose parents emigrated from India). Based on
      systems theory, a structural model depicting the linkage and temporal sequelae of
      mediating factors is presented. Risk and protective factors unique to Asian
      Indian adolescents--sociodemographic, family relationship, peer bonding,
      psychological, cultural, and ecological--are identified. Further, the impact of
      gender differences on family relationships is examined. Implications of the
      findings for drug use prevention policies, with special emphasis on developing
      comprehensive primary prevention strategies, are discussed.

PMID- 9583670
TI  - Can higher grades result in fewer friends? A reexamination of the relation
      between academic and social competence.
AB  - Although it has been widely assumed that the two domains of social and academic
      competence are independent, significant positive correlations have recently been
      found. The present study focused on peer judgments of social competence. Data on
      157 secondary school students revealed significant negative correlations. Further
      analysis was based on Coleman's (1961) explanation that intellectual students are
      willing to work hard at a relatively unrewarded activity. The results here
      confirm this view; a significant interaction effect was found for academic
      effort, academic subject, and academic achievement. It is argued that the
      contrasting correlations between academic and social competence may be explained
      by the various operationalizations of social competence.

PMID- 9583671
TI  - Expressed concerns of Yemeni adolescents.
AB  - This study examined the concerns of adolescents in the Republic of Yemen. A short
      version of the Mooney Problem Check List was administered to 150 13- to 17-year
      old males and females. Results indicated that the major concerns and problems
      reported by Yemeni adolescents were related to their vocational and educational
      future, recreational activities, religious matters, and school curriculum and
      teaching methods. Problems related to social life, family, and health and
      physical issues were less prominent. Results also showed that though there were
      similarities in the number of concerns expressed by males and females, males
      reported more difficulties with their vocational and educational future, marriage
      and sexual matters, and finances and employment, while females reported more
      problems with recreational activities, personal relationships, and health.

PMID- 9583672
TI  - Displaced adolescents in Croatia: sources of stress and posttraumatic stress
      reaction.
AB  - This study explored sources of stress and psychosocial reactions of adolescents
      displaced as a result of the war in the Republic of Croatia. The most frequent
      stressful events they faced were loss of home (80%), loss of personal belongings
      (66.7%), separation from family members (66.7%), damage to property (48.9%),
      exposure to enemy attacks (46.7%), and death of a family member or friend
      (37.8%). Among the most frequent posttraumatic stress reactions were intrusive
      images (48.9%), loss of interest (40.9%), restlessness (37.8%), appetite
      disturbances (33.3%), and increased irritability (31.1%). The exposure to a
      greater number of stressful events was related to increased depression. More
      posttraumatic stress reactions were evident in females, in adolescents who were
      exiled for longer periods, and in those whose parents were more anxious.
      Adolescents who manifested a higher number of stress reactions had poorer
      expectations regarding their future.

PMID- 9583673
TI  - Life and value orientations of Turkish university students.
AB  - This study investigated the value orientations of optimists and pessimists and
      the value structures of each group. The Life Orientation Test and the Rokeach
      Value Survey were administered to 285 university students in Ankara, Turkey.
      Results indicated that there were differences in the value orientations of
      optimists and pessimists. The examination of value structures of optimists and
      pessimists revealed that optimists were likely to give priority to self
      expansion, while pessimists tended toward self-restriction.

PMID- 9583674
TI  - How early adolescents describe their dreams: a quantitative analysis.
AB  - Most empirical research on dreams has focused on content and structure, while
      linguistic features have received far less attention. The present study
      investigated dream language in a critical developmental stage: early adolescence.
      Narratives of the dreams of 145 early adolescents were tape-recorded and
      transcribed, and the frequencies of various grammar forms and common words were
      calculated. The most common nouns for the entire sample were house and mother.
      The most frequent verbs were go and do. Males' dream narratives contained a
      greater number of such words as animal, long, enter, and kill. Females more often
      used intransitive verbs and such words as teacher, horse, and put. Several
      features differentiated older from younger early adolescents' dreams. The results
      indicate that linguistic features of dream narratives are affected by age and
      sex, displaying interesting parallels with clinical theories on dreams and early
      adolescence.

PMID- 9583676
TI  - The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction
      with RFXI, a protein that binds the enhancers of several viruses and cell-cycle
      regulated genes.
AB  - c-Abl, the non-receptor tyrosine kinase is associated with EP, a DNA element
      found in promoters/enhancers of different viruses and cell-cycle regulated genes.
      EP-DNA binds RFXI, a member of a novel family of DNA-binding proteins that is
      conserved through evolution and in yeast, it controls differentiation and exit
      from the mitotic cycle to G0. EP-associated proteins are preferentially tyrosine
      phosphorylated and the associated c-Abl has strong tyrosine kinase activity. Here
      we investigated the molecular mechanism underlying this c-Abl kinase activity. We
      show that RFXI and c-Abl are in direct interaction, in vitro and in cell
      extracts, through the RFXI proline rich (PxxP) motif and the c-Abl SH3 domain.
      Remarkably, this interaction significantly potentiates c-Abl but not v-Abl auto
      kinase activity. Collectively, we describe a novel mechanism of c-Abl recruitment
      to a defined DNA-cis element with its concomitant kinase activation. We propose
      that this mechanism may act to regulate cell-cycle control genes.

PMID- 9583675
TI  - Functional role for the c-Abl tyrosine kinase in meiosis I.
AB  - The c-Abl tyrosine kinase is activated by ionizing radiation and certain other
      DNA-damaging agents. The DNA-dependent protein kinase (DNA-PK) and the ataxia
      telangiectasia mutated (ATM) gene product, effectors in the DNA damage response,
      contribute to the induction of c-Abl activity. The present study demonstrates
      that c-Abl is expressed in mouse and rat testes, and predominantly in pachytene
      spermatocytes of meiosis I. The results also demonstrate that c-Abl interacts
      directly with meiotic chromosomes. In concert with a requirement for c-Abl at the
      pachytene stage, we show that, in contrast to wild-type mice, testes from Abl-/-
      mice exhibit defects in spermatogenesis. These findings provide the first
      demonstration that c-Abl plays a functional role in meiosis.

PMID- 9583677
TI  - Radioresistant MTp53-expressing rat embryo cell transformants exhibit increased
      DNA-dsb rejoining during exposure to ionizing radiation.
AB  - Recent data suggest that aberrant function of the wild type p53 protein (WTp53)
      may alter cellular survival following DNA damage through cellular pathways
      involving apoptosis and cell-cycle checkpoints, but little is known concerning
      it's possible role in DNA repair. In the present study, the ionizing radiation
      sensitivity was determined for a series of rat embryo fibroblast (REF) cell lines
      transfected with an activated form of the H-ras oncogene alone, or in combination
      with a variety of missense-mutant p53 (MTp53) alleles. Transformed REF clones
      which expressed exogenous MTp53 and p21ras proteins (CLASS II clones) were
      generally radioresistant in culture as determined by higher values for the
      surviving fraction after 2 Gy (SF2 value) and the radiation dose required to
      reduce survival to a fraction of 0.1 (D10 value), compared either to transformed
      REF clones expressing p21ras protein alone (CLASS I clones), or to non
      transfected REF control cell lines expressing baseline endogenous levels of
      p21ras and WTp53 protein. The increased radioresistance observed in the CLASS II
      clones (following both HDR- and LDR-irradiation), was significantly correlated
      with increased expression of MTp53 protein, and a decreased radiation-induced G1
      arrest response. The variability observed in clonogenic radiosensitivity among
      REF clones was not explained by differential radiation-induced apoptosis. Using
      the Comet assay performed after continuous low dose-rate (LDR)-irradiation, MTp53
      expressing REF clones were also found to be more proficient at the rejoining of
      DNA double-strand breaks (DNA-dsb), compared to WTp53-expressing REF clones.
      These results suggest that an enhanced DNA and cellular repair capacity may, in
      part, explain the increased radiation survival observed in some MTp53-expressing
      transformed fibroblasts and tumours.

PMID- 9583678
TI  - BAX frameshift mutations in cell lines derived from human haemopoietic
      malignancies are associated with resistance to apoptosis and microsatellite
      instability.
AB  - Bax suppresses tumorigenesis in a mouse model system and Bax-deficient mice
      exhibit lymphoid hyperplasia suggesting that BAX functions as a tumour suppressor
      in human haemopoietic cells. We examined BAX expression in 20 cell lines derived
      from human haemopoietic malignancies and consistent with a potential tumour
      suppressor function, identified two cell lines, DG75 (a Burkitt lymphoma cell
      line) and Jurkat (a T-cell leukaemia line), which lacked detectable BAX
      expression. Apoptosis of DG75 cells induced by low serum or ionomycin was
      significantly delayed relative to similar Burkitt lymphoma cell lines with normal
      BAX levels. Although DG75 and Jurkat cells expressed several BAX RNA species
      including the prototypical BAX alpha RNA, the absence of BAX protein was due to
      single base deletions and additions in a polyguanine tract within the BAX open
      reading frame. These frameshift mutations result in premature termination of
      translation and have recently also been identified in some colon cancers with
      microsatellite instability. Although mismatch repair defects are not considered a
      common feature of haemopoietic malignancies, DG75 and Jurkat cells had widespread
      microsatellite instability and did not express detectable levels of MSH2. In
      Jurkat cells, lack of MSH2 expression was due to a point mutation in exon 13 of
      MSH2 resulting in premature termination of translation. Our results suggest that
      a pathway linking mismatch repair defects, BAX tumour suppressor frameshift
      mutations and resistance to apoptosis may be a key feature of some lymphomas and
      leukaemias.

PMID- 9583679
TI  - Murine NIMA-related kinases are expressed in patterns suggesting distinct
      functions in gametogenesis and a role in the nervous system.
AB  - NIMA protein kinase is a major regulator of progression into mitosis in
      Aspergillus nidulans. Dominant negative forms of NIMA protein prevent entrance
      into mitosis in HeLa cells, suggesting that mammals have a similar pathway. We
      have reported previously the isolation of a murine NIMA-related kinase,
      designated Nek1, and more recently several additional NIMA-related human kinases
      have been cloned. The existence of several mammalian NIMA-related genes raises
      the questions of whether the different mammalian members have redundant,
      overlapping or distinct functions, and whether these functions are related to the
      role of NIMA in controlling mitosis. To address these questions we have studied
      the expression patterns of the different murine nek genes. To this end, we
      isolated a murine nek2 cDNA and compared its patterns of expression, during both
      gametogenesis and embryogenesis, to those of nek1. Both genes were highly
      expressed in developing germ cells, albeit in distinct patterns. In both females
      and males, nek1 is expressed much earlier than nek2, suggesting only limited
      ability for functional redundancy. Surprisingly, a striking specificity of nek1
      expression was found: high levels of nek1 RNA were observed in distinct regions
      of the nervous system, most notably in neurons of the peripheral ganglia. These
      patterns suggest that the different mammalian NIMA-related kinases participate in
      different phases of the meiotic process and may also have functions other than
      cell cycle control.

PMID- 9583680
TI  - Chromosomal instability is correlated with telomere erosion and inactivation of
      G2 checkpoint function in human fibroblasts expressing human papillomavirus type
      16 E6 oncoprotein.
AB  - Cell cycle checkpoints and tumor suppressor gene functions appear to be required
      for the maintenance of a stable genome in proliferating cells. In this study
      chromosomal destabilization was monitored in relation to telomere structure,
      lifespan control and G2 checkpoint function. Replicative senescence was
      inactivated in secondary cultures of human skin fibroblasts by expressing the
      human papillomavirus type 16 (HPV-16) E6 oncoprotein to inactivate p53.
      Chromosome aberrations were enumerated during in vitro aging of isogenic control
      (F5neo) and HPV-16E6-expressing (F5E6) fibroblasts. We found that structural and
      numerical aberrations in chromosomes were significantly increased in F5E6 cells
      during aging in vitro and fluorescence in situ hybridization (FISH) analysis
      using chromosome-specific probes demonstrated the occurrence of rearrangements
      involving chromosome 4 and 6 in genetically unstable F5E6 cells. Flow cytometry
      and karyotypic analyses revealed increased polyploidy and aneuploidy in F5E6
      cells only at passages > 16, although these cells displayed defective mitotic
      spindle checkpoint function associated with inactivation of p53 at passages 5 and
      16. G2 checkpoint function was confirmed to be gradually but progressively
      inactivated during in vitro aging of E6-expressing cells. Aging of F5neo
      fibroblasts was documented during in vitro passaging by induction of a senescence
      associated marker, pH 6.0 lysosomal beta-galactosidase. F5E6 cells displayed
      extension of in vitro lifespan and did not induce beta-galactosidase at high
      passage. Erosion of telomeres during in vitro aging of telomerase-negative F5neo
      cells was demonstrated by Southern hybridization and by quantitative FISH
      analysis on an individual cell level. Telomeric signals diminished continuously
      as F5neo cells aged in vitro being reduced by 80% near the time of replicative
      senescence. Telomeric signals detected by FISH also decreased continuously during
      aging of telomerase-negative F5E6 cells, but telomeres appeared to be stabilized
      at passage 34 when telomerase was expressed. Chromosomal instability in E6
      expressing cells was correlated (P < 0.05) with both loss of telomeric signals
      and inactivation of G2 checkpoint function. The results suggest that chromosomal
      stability depends upon a complex interaction among the systems of telomere length
      maintenance and cell cycle checkpoints.

PMID- 9583681
TI  - Recombinant PML adenovirus suppresses growth and tumorigenicity of human breast
      cancer cells by inducing G1 cell cycle arrest and apoptosis.
AB  - Our previous studies demonstrated that the promyelocytic leukemia gene, PML which
      involved in the 15;17 translocation in acute promyelocytic leukemia (APL) is a
      growth and transformation suppressor. In this study, recombinant PML adenovirus,
      Ad-PML was constructed and used to infect human breast cancer cells in vitro and
      in vivo, the anti-oncogenic function of PML and its mechanism of growth
      suppressing effect in breast cancer cells were examined. We showed that Ad-PML
      effectively infected the MCF-7 and SK-BR-3 cells. A high level of PML protein was
      expressed within 24 h post-infection and a detectable level remained at day 16.
      Ad-PML significantly suppressed the growth rate, clonogenicity, and
      tumorigenicity of breast cancer cells. Intratumoral injections of MCF-7-induced
      tumors by high titer Ad-PML suppressed tumor growth in nude mice by about 80%.
      The injection sites expressed high level of PML and associated with a massive
      apoptotic cell death. To elucidate the molecular mechanism of PML's growth
      suppressing function, we examined the effect of Ad-PML on cell cycle distribution
      in MCF-7 and SK-BR-3 cells. We found that Ad-PML infection caused a cell cycle
      arrest at the G1 phase. We further showed that G1 arrest of MCF-7 cells is
      associated with a significant decrease in cyclin D1 and CDK2. An increased
      expression of p53, p21 and cyclin E was found. The Rb protein became
      predominantly hypophosphorylated 48 h post-infection. These findings indicate
      that PML exerts its growth suppressing effects by modulating several key G1
      regulatory proteins. Our study provides important insight into the mechanism of
      tumor suppressing function of PML and suggests a potential application of Ad-PML
      in human cancer gene therapy.

PMID- 9583682
TI  - A cis-acting peptide signal in human immunodeficiency virus type I Rev which
      inhibits nuclear entry of small proteins.
AB  - A peptide signal, which may control nucleo-cytoplasmic protein trafficking, was
      newly identified in human immunodeficiency virus type I (HIV-1) Rev, a lentiviral
      post-transcriptional transactivator. The sequence, in the amino-terminal portion
      of HIV-1 Rev, maintains a Rev mutant with a dysfunctional nuclear/nucleolar
      targeting signal outside of the nucleus, although this Rev molecule itself is
      small enough to pass through the nuclear pores. Transition of this sequence to
      the N-terminus of human T-lymphocytic leukemia/lymphoma virus type I (HTLV-I)
      p21x, which is usually located evenly distributed throughout the cell, resulted
      in capture of p21x in the cytoplasm. Mutational analysis clarified that a 14
      residue peptide sequence was sufficient to display this inhibitory effect against
      nuclear entry. Furthermore, this HIV-1 Rev sequence was capable of inhibiting
      nuclear entry of a fragment of a human ribosomal protein, when it was fused to
      the carboxy terminus. The identified nuclear entry inhibitory signal (NIS)
      contains a conserved hydrophilicity motif, which forms an amphipathic helix.
      Significantly, this motif and its helical structure were shown to be important
      for NIS function and the HIV-1 Rev function itself. Possible roles for NIS as a
      molecular anchor are proposed herein.

PMID- 9583683
TI  - Molecular analysis of the FHIT gene in human prostate cancer.
AB  - A variety of studies suggest that the FHIT gene, which encompasses the fragile
      site at 3p14.2, is a candidate tumor suppressor gene in several forms of human
      cancer. To determine whether the FHIT gene is altered in prostate carcinomas, we
      examined 15 prostate tumors, four normal prostate tissue specimens and RNA from a
      pool of 62 normal human prostate tissues (Clontech) for the integrity of FHIT
      transcripts, using a robust single-stage PCR and a nested PCR method. In each
      case a major FHIT-specific full-length product was observed. Additional
      aberrantly sized products, which were more numerous in the nested PCR strategy,
      were present at a far lower level than the full-length transcripts in 14 of 15
      tumors, three of four normal human prostate tissues and in the pooled normal
      prostate RNA. Sequence analysis revealed that these aberrant products
      corresponded to alternatively spliced FHIT transcripts, which were neither more
      numerous nor more prominent in the tumors than in the normal prostate specimens.
      Deletion at the FHIT locus was also evaluated by using three intragenic
      polymorphic markers (D13S1481, D3S1300, and D3S1234). Allelic loss was observed
      in two tumors, but these genomic alterations did not correspond to the aberrant
      FHIT transcripts. DNA analysis, furthermore, suggested that the tumor
      heterogeneity was not a likely explanation for presence of normal and
      alternatively spliced FHIT transcripts in the prostate tumors. In conclusion, we
      detected neither frequent loss of heterozygosity nor tumor specific transcripts
      of the FHIT gene in human prostate cancer.

PMID- 9583684
TI  - The NPC derived C15 LMP1 protein confers enhanced activation of NF-kappa B and
      induction of the EGFR in epithelial cells.
AB  - The Epstein-Barr Virus (EBV) LMP1 protein is frequently expressed in
      nasopharyngeal carcinoma and is essential for the transforming effects of EBV.
      Analysis of LMP1 genes isolated from tumor biopsies has revealed considerable
      sequence variation including deletion of amino acids 343-352. Several studies
      have suggested that this sequence variation could enhance the transforming
      potential of LMP1. LMP1 has profound effects on cellular gene expression mediated
      in part through activation of the NF-kappa B transcription factor. In addition,
      LMP1 engages the TRAF signaling pathway resulting in the induction of EGFR
      expression. In this study, the LMP1 proteins derived from the laboratory strain
      B95-8 and the NPC strain C15 were analysed for their ability to activate NF-kappa
      B and also to induce expression of the EGFR. The data suggest that the C15-LMP1
      protein activates NF-kappa B more efficiently and induces higher levels of the
      EGFR. Analysis of chimeric LMP1 proteins indicates that the amino terminal 181
      amino acids of C15-LMP1 confer this increased signaling capability, and that
      deletion of amino acids 343-352 does not affect these properties. Finally, these
      data provide evidence that five amino acid changes within the transmembrane
      domain in the C15-LMP1 protein lead to enhanced NF-kappa B activation and EGFR
      induction.

PMID- 9583685
TI  - Evaluation of an autoregulatory tetracycline regulated system.
AB  - Tetracycline controlled gene expression systems have become powerful tools in the
      analysis of gene function in mammalian cell culture as well as transgenic animals
      and plants. The original description of a tetracycline-regulated gene expression
      system is based on two plasmids, one of which constitutively expresses a
      tetracycline-controlled transactivator protein (tTA), a fusion protein between
      the tetracycline repressor of E. coli and the transcriptional activation domain
      of the VP16 protein of herpes simplex virus. The second plasmid contains the gene
      to be regulated by tTA under the control of an inducible promoter which consists
      of seven copies of the tetracycline resistance operator (tetO). Since this
      original description, many modifications have been described. In this report, we
      evaluate an autoregulatory tetracycline controlled system, in which the tTA is
      itself under the control of the tetO. We demonstrate that this autoregulatory
      tetracycline system produces adverse effects including cellular morphologic
      changes, growth rate attenuation and alterations in cell cycle distribution.

PMID- 9583686
TI  - Type I interferon induction of the Cdk-inhibitor p21WAF1 is accompanied by
      ordered G1 arrest, differentiation and apoptosis of the Daudi B-cell line.
AB  - We show, in this study, that type I IFN induction of the cyclin-dependent kinase
      (cdk) inhibitor p21WAF1 in the human Burkitt lymphoma B cell-line Daudi and
      ensuing cell cycle arrest correlate with the terminal differentiation of these
      cells, and is ultimately followed by apoptosis and cell death. The expression of
      p21WAF1 paralleled the onset of G1 arrest and the reduction of surface IgM
      expression which was used as a marker of the differentiation response, and the
      IFN treated cells acquired a typical plasma cell-like morphology. The type II IFN
      IFNgamma, which does not inhibit the growth of Daudi cells, did not induce the
      expression of p21WAF1, nor affect the expression of surface IgM. The induction of
      p21WAF1 which paralleled the inhibition of the phosphorylation of the
      retinoblastoma protein, pRB, was preceded by the strong reduction in c-myc
      levels. We propose that the coupled down-regulation of c-myc and induction of
      p21WAF1 may be crucial to the induction of differentiation and G1 arrest in Daudi
      cells by type I IFN. Growth arrest and differentiation was followed by apoptosis
      and cell death, and was accompanied by the induction of the activity of the
      apoptotic ICE-family protease CPP32. G1 arrest and differentiation followed by
      apoptotic cell death are characteristics of terminal differentiation. Thus, our
      data suggest that the induction of p21WAF1 and G1 arrest mediated by type I IFN
      in Daudi cells is part of terminal differentiation response in these cells,
      highlighting a role for type I IFN as B cell terminal differentiation factors.

PMID- 9583687
TI  - Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14
      in B-cell chronic lymphocytic leukemia and mantle cell lymphoma.
AB  - Deletions affecting the interval between the RB1 gene and marker D13S25 at band
      13q14 are the most frequent genetic abnormalities of B-cell chronic lymphocytic
      leukemia (B-CLL) and indicate the presence of a novel tumor suppressor gene in
      this region. In the current study, a high resolution physical map of fragments
      spanning one megabasepair (Mb) of genomic DNA at the critical 13q14 segment was
      constructed. To define the minimal region of loss within the RB1 and D13S25
      interval, we screened 322 B-CLLs for deletions at either of the two loci. Thirty
      mantle cell lymphomas (MCLs) were included in the analysis because we observed a
      13q14 deletion pattern similar to B-CLL in this disease. The incidence of 13q14
      deletions was 51% in B-CLL and 70% in MCL, respectively. No frequent loss of the
      BRCA2 gene at band 13q12 was found. Detailed deletion mapping at band 13q14 with
      probes from the RB1-D13S25 interval lead to the identification of a critical
      deletion region 400 kb in size. Within this region two segments were most
      frequently affected, one at D13S272 120 kb in size and another 240 kb distal of
      D13S272 80 kb in size. From these two segments expressed sequences were
      identified as candidates for the putative 13q14 tumor suppressor gene involved in
      the pathogenesis of B-CLL and MCL.

PMID- 9583688
TI  - Abrogation of c-Raf expression induces apoptosis in tumor cells.
AB  - Signal transduction pathways involving the c-Raf protein kinase are frequently
      activated in tumor cells. We have addressed the relevance of this activation by a
      loss-of-function approach. An anti-sense phosphorothioate oligonucleotide (ODN)
      specifically targeted against c-raf mRNA (Monia et al., 1996a) was used to block
      c-Raf protein expression in four different cell lines derived from lung,
      cervical, prostate and colon carcinomas. Concomitant with the abrogation of c-Raf
      expression we observed the occurrence of classical apoptotic markers, including
      chromatin condensation, inter-nucleosomal DNA cleavage, annexin V binding and
      cleavage of PARP, which was followed by cell death, affecting most of the cell
      population. This induction of apoptosis occurred independent of the p53 status of
      the cell. These findings demonstrate that c-Raf can protect tumor cells from
      undergoing programmed cell death, and suggest that the interference with c-Raf
      expression or function by ODNs or specific drugs could represent a powerful means
      for improving the efficacy of anti-cancer therapy.

PMID- 9583689
TI  - Standardized perioperative care protocols and reduced length of stay after colon
      surgery.
AB  - BACKGROUND: Recent studies have suggested that critical pathways and standard
      order sets decrease hospital length of stay and improve quality of care. A
      recently conducted prospective, randomized study at our institution found that
      patients undergoing elective colon resections had earlier return of bowel
      function if perioperative epidural anesthesia and analgesia were provided. All
      patients in the study were also placed on a standardized perioperative regimen.
      We hypothesized that the standardized perioperative protocol used in this study
      contributed to early return of bowel function and hospital discharge compared
      with similar patients managed off protocol. STUDY DESIGN: To test this
      hypothesis, we performed a case-controlled study comparing the hospital courses
      of 36 study patients to 36 control patients undergoing colorectal surgery by the
      same surgeons during the same calendar year. The distribution of types of
      operations and anesthetic techniques was similar in both groups. RESULTS: As
      dictated by the protocol, all study patients had their nasogastric tubes removed,
      were started on a low fat liquid diet, and ambulated in the first postoperative
      day. Nasogastric tubes were removed in control patients and study patients 2.2 +/
      0.9 (mean value +/- SD) and 1.0 +/- 0.0 days postoperatively, respectively.
      Control patients were started on an oral diet, usually clear liquids, an average
      of 2.9 +/- 1.1 days postoperatively, a specific liquid diet was started 1.0 day
      postoperatively in study patients (p < 0.001). Return of bowel function, as
      determined by bowel tones, flatus, and bowel movements, occurred approximately 1
      day earlier in study patients. Study patients were discharged 1 day sooner than
      control patients. CONCLUSIONS: Our results suggest that the return of bowel
      function and the length of stay of patients undergoing colon surgery are improved
      if patients are entered into a standardized protocol that eliminates variation in
      intraoperative and postoperative anesthesia and postoperative surgical care. We
      believe these results can be reproduced in routine clinical surgery by having a
      clearly outlined protocol for perioperative care similar to that used in this
      study.

PMID- 9583690
TI  - Management of pancreatic pseudocysts.
AB  - BACKGROUND: Operative internal drainage has been standard treatment for chronic
      unresolved pancreatic pseudocysts (PPs). Recently, percutaneous external drainage
      (PED) has become the primary mode of treatment at many medical centers. STUDY
      DESIGN: A retrospective chart review was performed of 96 patients with PPs who
      were managed between 1987 and 1996. Longterm followup information was obtained by
      telephone and mail questionnaire. RESULTS: Twenty-seven patients underwent
      computed tomographic (CT)-guided PED. PP resolution occurred in 17 patients.
      Clinical deterioration or secondary infection mandated urgent pancreatic
      debridement in 7 (26%) patients and cystgastrostomy in 2 (7%) patients. There was
      one hospital death in this group. Thirty-two patients underwent cystgastrostomy
      or cystjejunostomy (n = 21), distal pancreatectomy (n = 8), pancreatic
      debridement and external drainage (n = 2), or cystectomy (n = 1). Two (6%)
      patients required postoperative pancreatic debridement for failure of resolution
      and peritonitis and two patients underwent PED of abscess. There was one hospital
      death in the expectantly managed group of 37 patients. Median followup of 3 years
      (range, 0.5-9.3 years) in 66 patients revealed that 6, 3, and 4 patients of PED,
      surgery, and expectantly managed groups, respectively, had radiologic evidence of
      recurrent PPs. CONCLUSIONS: Operative management for PPs appears to be superior
      to CT-guided PED. Although the later was often successful, it required major
      salvage procedures in one third of the patients. An expectant management protocol
      may be suitable for selected patients.

PMID- 9583692
TI  - Lethal injuries and time to death in a level I trauma center.
AB  - BACKGROUND: The purpose of this study was to identify the causes and time to
      death of all trauma victims who died at a level I trauma center during an 11-year
      period. STUDY DESIGN: Autopsies were performed on all patients who died secondary
      to trauma. Retrospective review of these autopsies was carried out and appended
      to existing trauma registry data. Standard definitions were used to attribute the
      cause of death in each case. Preventable deaths were determined by a standardized
      peer review process. RESULTS: Between January 1985 and December 1995, a total of
      900 trauma patients died. This represented 7.3% of all major trauma admissions
      (12,320). Seventy percent of these patients died within the first 24 hours of
      admission. Thoracic vascular and central nervous system (CNS) injuries were the
      most common causes of death in the first hour after admission to the hospital.
      CNS injuries were the most common causes of death within the 72 deaths after
      admission. Acute inflammatory processes (multiple organ failure, acute
      respiratory distress syndrome, and pneumonia) and pulmonary emboli were the
      leading causes of death after the first 72 hours. Overall, 43.6% (393 of 900) of
      all trauma deaths were caused by CNS injuries, making this the most common cause
      of death in our study. The preventable death rate was 1%. CONCLUSIONS: The first
      24 hours after trauma are the deadliest for these patients. Primary and secondary
      CNS injuries are the leading causes of death. Prevention, early identification,
      and treatment of potentially lethal injuries should remain the focus of those who
      treat trauma patients.

PMID- 9583691
TI  - Clinical intestinal transplantation: new perspectives and immunologic
      considerations.
AB  - BACKGROUND: Although tacrolimus-based immunosuppression has made intestinal
      transplantation feasible, the risk of the requisite chronic high-dose treatment
      has inhibited the widespread use of these procedures. We have examined our 1990
      1997 experience to determine whether immunomodulatory strategies to improve
      outlook could be added to drug treatment. STUDY DESIGN: Ninety-eight consecutive
      patients (59 children, 39 adults) with a panoply of indications received 104
      allografts under tacrolimus-based immunosuppression: intestine only (n = 37);
      liver and intestine (n = 50); or multivisceral (n = 17). Of the last 42 patients,
      20 received unmodified adjunct donor bone marrow cells; the other 22 were
      contemporaneous control patients. RESULTS: With a mean followup of 32 +/- 26
      months (range, 1-86 months), 12 recipients (3 intestine only, 9 composite grafts)
      are alive with good nutrition beyond the 5-year milestone. Forty-seven (48%) of
      the total group survive bearing grafts that provide full (91%) or partial (9%)
      nutrition. Actuarial patient survival at 1 and 5 years (72% and 48%,
      respectively) was similar with isolated intestinal and composite graft
      recipients, but the loss rate of grafts from rejection was highest with intestine
      alone. The best results were in patients between 2 and 18 years of age (68% at 5
      years). Adjunct bone marrow did not significantly affect the incidence of graft
      rejection, B-cell lymphoma, or the rate or severity of graft-versus-host disease.
      CONCLUSIONS: These results demonstrate that longterm rehabilitation similar to
      that with the other kinds of organ allografts is achievable with all three kinds
      of intestinal transplant procedures, that the morbidity and mortality is still
      too high for their widespread application, and that the liver is significantly
      but marginally protective of concomitantly engrafted intestine. Although none of
      the endpoints were markedly altered by donor leukocyte augmentation (and
      chimerism) with bone marrow, establishment of the safety of this adjunct
      procedure opens the way to further immune modulation strategies that can be added
      to the augmentation protocol.

PMID- 9583693
TI  - Role of adhesion molecule expression and soluble fractions in hepatic resection.
AB  - BACKGROUND: Little has so far been documented about the relationship between
      liver injury and adhesion molecules. The aim of this study is to clarify the role
      of adhesion molecules in hepatic resection by studying both the expression of
      such adhesion molecules and the measurement of their soluble fractions in the
      blood. STUDY DESIGN: To study adhesion molecule expression in the liver, liver
      biopsies were obtained before and after hepatectomy in 14 patients. Using frozen
      sections, immunochemical staining for intercellular adhesion molecule-1 (ICAM-1)
      and vascular cell adhesion molecule-1 (VCAM-1) was then performed. To study the
      soluble fractions of adhesion molecules in the hepatic venous blood, the serum
      soluble fractions of ICAM-1 and VCAM-1 from another 17 patients were measured
      using an enzyme-linked immunosorbent assay. The plasma levels of
      polymorphonuclear leukocyte (PMN) elastase were also measured using an enzyme
      immunoassay. Both the preoperative and postoperative values of the serum soluble
      fractions of ICAM-1, VCAM-1, and PMN elastase were then compared. The correlation
      between their values and the perioperative variables was also investigated.
      RESULTS: Either ICAM-1 or VCAM-1 was stained on the sinusoidal endothelial cells
      and Kupffer cells or circulating PMNs in the sinusoid. The positive rate of
      either ICAM-1 or VCAM-1 staining in livers with more than 40 minutes of total
      ischemic time (80%) was significantly higher than that in livers with less than
      40 minutes of total ischemic time (0%; p < 0.05). The incidence of postoperative
      complications in the ICAM-1 positive staining group tended to be higher than that
      in the ICAM-1 negative group. Both soluble fractions of ICAM-1 and VCAM-1 in
      patients with cirrhotic liver disease were also significantly higher than those
      in patients with a normal liver. The soluble VCAM-1 level in patients with a
      chronic active hepatitic liver tended to be higher than that in those with a
      nonactive hepatitic liver. The preoperative level of soluble ICAM-1 correlated
      with that ofVCAM- 1, PMN elastase, albumin, aspartate aminotransferease (AST),
      and the indocyanine green dye retention test at 15 minutes (ICG R15), while the
      preoperative level of VCAM-1 correlated with albumin, the hepaplastin test, AST,
      and ICG R15. Both the serum soluble ICAM-1 and VCAM-1 levels after hepatectomy
      were significantly lower than those before hepatectomy. By contrast, the
      posthepatectomy level of PMN elastase was significantly higher than its
      prehepatectomy level. The difference between the postoperative and preoperative
      values of soluble ICAM-1 correlated with the postoperative AST level,
      postoperative alanine aminotransferase level, and total ischemic time.
      CONCLUSIONS: Adhesion molecules were expressed in the liver after hepatic
      resection, and such expression correlated with a total ischemic time during
      hepatectomy. In addition, judging from the soluble forms of such molecules, these
      adhesion molecules play an important role in hepatic resection.

PMID- 9583694
TI  - Minimally invasive surgery: the pediatric surgery experience.
AB  - BACKGROUND: Minimally invasive surgery (MIS) has become an important aspect of
      general surgery. The degree to which pediatric surgeons have incorporated MIS
      into their practice is not known. STUDY DESIGN: An MIS survey was sent to all
      members of the American Pediatric Surgical Association. Respondents were
      separated into two groups: nonperformers and performers of MIS. Performers were
      asked how they were trained in MIS and the total number and types of minimally
      invasive procedures they have performed. RESULTS: Eighty-two percent of surveyed
      pediatric surgeons perform MIS. Eighty-seven percent received some or all of
      their training in a postgraduate course. Two percent received their only training
      during their general surgery residency. Forty-seven percent of performers
      reported 50 or fewer total procedures. A wide variety of procedures were
      reported, but laparoscopic cholecystectomy (95%) was the procedure most
      frequently reported. Thoracoscopic procedures (71%) were also reported at high
      rates. CONCLUSIONS: Most pediatric surgeons in our survey perform MIS. The high
      rate of laparoscopic cholecystectomies reported suggests that the initial MIS
      experience of pediatric surgeons in our survey is similar to adult general
      surgeons. The frequency, however, of thoracic cases reported indicates that MIS
      techniques are being applied to all areas of pediatric surgery. The total
      minimally invasive procedure experience of our respondents also suggests that
      pediatric surgeons are early in their learning curve.

PMID- 9583695
TI  - Laparoscopic versus open appendectomy: a metaanalysis.
AB  - BACKGROUND: There have been numerous retrospective and uncontrolled series of
      laparoscopic appendectomy (LA), as well as 16 prospective randomized studies
      published to date. Although most of these have concluded that the laparoscopic
      technique is as least as good as open appendectomy (OA), there has been
      considerable controversy as to whether LA is superior. To help clarify this
      issue, we performed a metaanalysis of the randomized prospective studies. STUDY
      DESIGN: A metaanalysis of all formally randomized prospective trials of LA versus
      OA in adults. RESULTS: A total of 1,682 patients were analyzed. When compared
      with OA, LA results in significantly less postoperative pain, earlier resumption
      of solid foods, a shorter hospital stay, and a faster return to normal
      activities. The wound infection rate in the LA patients is less than one half the
      rate in patients undergoing OA. LA, however, requires longer operating times and
      the incidence of intraabdominal abscess is higher, but this failed to reach
      statistical significance. There were no differences in complications or hospital
      charges. CONCLUSIONS: LA offers considerable advantages over OA, primarily
      because of its ability to reduce the incidence of wound infections and shorten
      recovery times. Its widespread acceptance should be considered. The trend toward
      increased intraabdominal abscess formation is worrisome, however, and demands
      further investigation.

PMID- 9583696
TI  - The evolution and maturation of laparoscopic cholecystectomy in an academic
      practice.
AB  - BACKGROUND: The technique of laparoscopic cholecystectomy (LC) has evolved since
      its adoption in the late 1980s. We sought to document these changes and assess
      whether patient outcomes were influenced during this maturational process. STUDY
      DESIGN: A prospective data base was used to record the outcomes of all LCs
      performed in an academic surgeon's practice. Trends over time among 1,165
      consecutive patients were assessed by comparing the first 100 LCs (group I), the
      middle 100 LCs (group II), and the most recent 100 LCs (group III). RESULTS:
      During a 93-month period with 1,165 patients undergoing LC, 25 procedures (2.1%)
      were converted to open cholecystectomy. Perioperative complications occurred in
      31 patients (3%): grade I in 9 (0.8%), grade II in 16 (1.4%), grade III in 5
      (0.4%), and grade IV (death) in 1 (0.1%). Length of hospital stay and
      convalescence were 1.1 +/- 0.1 and 9.5 +/- 0.5 days, respectively. Nineteen
      patients (2%) were readmitted early after operation and 10 (1%) developed long
      term complications (port-site hernia or retained stone). In group III,
      cholangiography was largely replaced by intraoperative ultrasonography for ductal
      evaluation. Operating room time decreased, while the rates of conversion,
      morbidity, and readmission remained the same. Patients had higher ASA
      classifications in the latter two groups, whereas operative charges were greater
      in Group III than in Groups I and II. These trends occurred even though most
      procedures are currently performed by residents, and fewer LCs are being done.
      CONCLUSIONS: Laparoscopic cholecystectomy has matured into a more efficient
      operation, yet remains safe with low morbidity when performed by residents at an
      academic institution.

PMID- 9583697
TI  - Prognostic analysis of survival in small breast cancers.
AB  - BACKGROUND: Routine axillary dissection in patients with invasive small breast
      cancer remains controversial. We previously reported a model for predicting nodal
      involvement in patients with T1a or T1b breast cancer that may guide the practice
      of selective nodal dissection. The objective of this study was to determine
      whether the prognosticators that predict nodal metastases also predict survival.
      STUDY DESIGN: This study is a retrospective review of 2,153 women with small
      invasive breast cancer (< or = 1 cm) diagnosed between January 1984 and December
      1995. Cases were identified from a statewide tumor registry, the Hospital
      Association of Rhode Island, and the tumor registry at Baystate Medical Center in
      Massachusetts. The impact on survival of patient age (< or = 40 versus > 40
      years), nodal status (positive versus negative), tumor size (T1a versus T1b), and
      tumor grade (1 versus 2 or 3) were analyzed. Breast cancer-specific survival
      (BCSS) was analyzed using the Kaplan-Meier method and the proportional hazards
      regression method. RESULTS: There were 388 patients with tumors 0.5 cm or less
      (T1a) and 1,765 with tumors 0.6-1.0 cm (T1b). Nodal status was known in 68% of
      cases (1,461 of 2,153), and tumor grade was recorded in 42% of cases (902 of
      2,153). In univariate analysis, age, grade, and nodal status were significant in
      their association with BCSS. Tumor size did not influence BCSS among patients
      with small invasive tumors. Women older than 40 years had superior survival
      compared with younger women (93% versus 78% at 5 years; p = 0.01). Similarly,
      women with low grade (1) tumors did better than those with higher grade (2 or 3)
      tumors (98% versus 88% at 5 years; p = 0.03). The 5-year BCSS was 96% versus 78%
      for node-negative versus node-positive disease, and the 10-year BCSS was 91%
      versus 62% (p = 0.001). In the multivariate analysis, age and nodal status
      remained firmly associated with survival, although grade lost its significance.
      CONCLUSIONS: Small tumor size does not affect survival. Although risk profiles
      for nodal involvement can be constructed to help guide the practice of selective
      axillary lymphadenectomy in patients with small invasive breast cancers, these
      factors cannot serve as a surrogate to nodal status in establishing patient
      prognosis. Nodal status remains the most powerful determinant of survival in
      breast cancer patients, even those with very small tumors.

PMID- 9583698
TI  - Surgeons and interventional radiologists: doing what's best for the patient.

PMID- 9583699
TI  - Stage I rectal cancer: identification of high-risk patients.
AB  - BACKGROUND: Stage I rectal cancer (T1, T2 N0) is currently treated by surgical
      resection alone. Despite adequate surgical resection, approximately 10-15% of
      patients will develop recurrence. Identification of patients at high risk for
      recurrence could potentially lead to an improvement in outcome by selection of
      these patients for adjuvant therapy. METHODS: Between June 1986 and September
      1996, 211 patients with primary rectal cancer (stage I) were treated by radical
      surgical resection alone. The medical data of all patients were entered into a
      database and prospectively followed. The following 10 prognostic factors were
      correlated with recurrence and tumor-related mortality: patient factors: age,
      gender, and preoperative carcinoembryonic antigen level; tumor factors: location
      from the anal verge (< 6 cm vs. > or = 6 cm), T stage (T1 vs. T2), intratumoral
      blood vessel invasion (BVI), intratumoral lymphatic vessel invasion, presence of
      tumor ulceration, and histologic differentiation; and treatment-related factors:
      extent of surgical resection--abdominal perineal resection versus low anterior
      resection. Univariate analysis of the effect of the prognostic factors on
      recurrence and tumor-related mortality were performed by the method of Kaplan
      Meier and log rank test. Independent prognostic factors were determined by a
      multivariate analysis performed using the Cox proportional hazards model.
      RESULTS: The overall 5-year actuarial recurrence was 12% and tumor-related
      mortality was 10%. Independent predictors of recurrence were male gender and BVI.
      Independent predictors of tumor-related mortality were male gender, BVI, and
      poorly differentiated tumors. CONCLUSIONS: Despite radical resection, patients
      with stage I rectal cancer with male gender, BVI, and poorly differentiated
      tumors should be considered high-risk patients.

PMID- 9583700
TI  - Fifteen-year experience in axillofemoral bypass with externally supported knitted
      Dacron prosthesis in a Japanese hospital.
AB  - BACKGROUND: Recently, several reports in the United States have demonstrated
      remarkable improvement in the patency of axillofemoral (AXF) bypass with an
      externally supported prosthesis. The purpose of this study was to review the
      prognoses regarding graft patency, limb salvage, and survival of patients who
      underwent AXF bypass grafting with an externally supported, knitted Dacron
      prosthesis (EXS) in a Japanese hospital and to analyze what factors affected the
      graft patency. METHODS: The clinical records of 81 patients with arteriosclerosis
      obliterans (ASO) who underwent 47 axillounifemoral bypasses and 34
      axillobifemoral bypasses with EXS were retrospectively checked and, by uni- and
      multivariate analysis, perioperative factors were evaluated. RESULTS: The
      cumulative primary and secondary patency rates of AXF bypass grafts were 81% and
      88%, 73% and 80%, and 70% and 77% at 3, 5, and 7 years, respectively, with no
      change thereafter. Limb salvage rate was 100%. The operative mortality was 3.7%
      and the survival rate was 63%, 41%, and 35% at 3, 5, and 7 years, respectively.
      The risk factors adversely affecting the patency were age (younger than 75
      years), poor distal runoff, and preoperative leukocyte count (more than
      8,000/microL) by univariate analysis, none of which were significant by stepwise
      multivariate analysis. CONCLUSIONS: AXF bypass using EXS was an acceptable
      procedure in ASO patients at high risk for conventional anatomic bypass or with
      limited life expectancy, and there was no significant risk factor that
      independently affected the patency.

PMID- 9583702
TI  - Intraabdominal pressure: a revised method for measurement.

PMID- 9583701
TI  - Standardized perioperative care protocols and reduced lengths of stay after colon
      surgery.

PMID- 9583703
TI  - Acid reflux test for gastroesophageal reflux after distal gastrectomy: diagnosis
      and clinical effect of cisapride.

PMID- 9583704
TI  - Reconstruction after proximal gastrectomy using a stapled, U-shaped jejunal
      pouch.

PMID- 9583705
TI  - Vascular injuries during laparoscopy.

PMID- 9583706
TI  - Definition of early gastric cancer and Dukes's A tumor.

PMID- 9583707
TI  - Ischemic liver injury.

PMID- 9583708
TI  - Invited commentary: Re: "Multiple comparisons and related issues in the
      interpretation of epidemiologic data".

PMID- 9583709
TI  - Multiple comparisons, explained.

PMID- 9583710
TI  - Describing data requires no adjustment for multiple comparisons: a reply from
      Savitz and Olshan.

PMID- 9583711
TI  - Colorectal cancer: another complication of diabetes mellitus?
AB  - Delayed stool transit and other gastrointestinal abnormalities are commonly
      observed in persons with diabetes mellitus and are also known to be associated
      with colorectal cancer. Previous studies of the contribution of diabetes to
      colorectal cancer incidence and mortality have been limited by small sample sizes
      and failure to adjust for covariates. With more than 1 million respondents, the
      1959-1972 Cancer Prevention Study provided a unique opportunity to explore
      whether persons with diabetes (n=15,487) were more likely to develop colorectal
      cancer during a 13-year follow-up period than were persons without diabetes
      (n=850,946). After adjustment for colorectal cancer risk factors, such as race,
      educational level, body mass index, smoking, alcohol use, dietary intake, aspirin
      use, physical activity, and family history of colorectal cancer, the incidence
      density ratio comparing colorectal cancer in those with diabetes and those
      without diabetes was 1.30 (95% confidence interval 1.03-1.65) for men and 1.16
      (95% confidence interval 0.87-1.53) for women. However, diabetes was not
      associated with greater case fatality. Future studies should explore the
      possibility of a cancer-promoting gastrointestinal milieu, including delayed
      stool transit and elevated fecal bile acid concentrations, associated with
      hyperglycemia and diabetic neuropathy.

PMID- 9583712
TI  - Population attributable fraction estimation for established breast cancer risk
      factors: considering the issues of high prevalence and unmodifiability.
AB  - Established breast cancer risk factors, in addition to being relatively
      unmodifiable, are highly prevalent among US women. Previous reports of population
      attributable fraction for the established risk factors have used definitions that
      resulted in 75-100% of women in the source population labeled exposed. The
      practical value of such estimates has not been discussed; further, the estimates
      have frequently been misinterpreted. In the context of examining the
      interpretation and public health value of such estimates, the authors demonstrate
      the sensitivity of the population attributable fraction to changes in exposure
      cutpoints. They use data from the Carolina Breast Cancer Study, a case-control
      study of breast cancer conducted in North Carolina between 1993 and 1996. For the
      four established risk factors (menarche before age 14 years, first birth at age
      20 years or later/nulliparity, family history of breast cancer, and history of
      benign breast biopsy), the estimated population attributable fraction was 0.25
      (95% confidence interval 0.06-0.48). Over 98% of the source population was
      exposed to at least one of these risk factors. The population attributable
      fraction estimate was reduced to 0.15 when more restrictive definitions of early
      menarche (less than age 12 years) and late age at first full-term pregnancy (30
      years or more) were used (proportion exposed, 0.62). Population attributable
      fractions for established breast cancer risk factors probably have little public
      health value because of both the high proportions exposed and the relative
      unmodifiability of the risk factor distributions.

PMID- 9583713
TI  - Direct and indirect estimates of HIV-1 incidence in a high-prevalence population.
AB  - While the worldwide AIDS epidemic continues to expand, directly measured
      incidence data are difficult to obtain. Methods to reliably estimate human
      immunodeficiency virus type 1 (HIV-1) incidence from more easily available data
      are particularly relevant in those parts of the world where prevalence is rising
      in heterosexually exposed populations. The authors set out to estimate HIV-1
      incidence in a population of heterosexual sexually transmitted disease clinic
      attendees in Trinidad who had a known high prevalence of HIV-1 subtype B. Over
      the period 1987-1995, HIV-1 incidence estimates from serial cross-sectional
      studies of HIV-1 prevalence, passive follow-up of clinic recidivists, modeling of
      early markers of HIV-1 infection (p24 antigen screening), and a cohort study of
      seronegative genital ulcer disease cases were compared. Measuring incidence
      density in the genital ulcer disease cases directly gave the highest estimate,
      6.9% per annum. Screening for the detection of early HIV-1 markers yielded an
      incidence of 5.0% per annum, while estimating incidence from serial cross
      sectional prevalence data and clinic recidivists gave estimates of 3.5% and 4.5%
      per annum, respectively. These results were found to be internally consistent.
      Indirect estimates of incidence based on prevalence data can give accurate
      surrogates of true incidence. Within limitations, even crude measures of
      incidence are robust enough for health planning and evaluation purposes. For
      planning vaccine efficacy trials, consistent conservative estimates may be used
      to evaluate populations before targeting them for cohort studies.

PMID- 9583714
TI  - Effect of HIV/AIDS versus other causes of death on premature mortality in New
      York City, 1983-1994.
AB  - This study examined years of potential life lost (YPLL) before age 65 years to
      assess the relative impact of human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS) versus other leading causes of death on
      premature mortality in New York City, New York, between 1983 and 1994. Most
      causes of death showed substantial year-to-year variation in YPLL, with the
      exception of HIV/AIDS. The YPLL attributed to HIV/AIDS increased monotonically
      from 11,866 in 1983 to 167,317 in 1994, a nearly 15-fold increase. The rank order
      of the relative contribution of HIV/AIDS to total YPLL changed from the eighth
      leading cause of death to the leading cause. YPLL from heart disease, which
      ranked second in 1983, declined to fourth in 1994, homicide was unchanged, and
      chronic liver disease declined from fifth to ninth rank. The annual YPLL
      attributed to malignant neoplasms was similar to that for heart disease, but
      peaked in 1984, and the reduction over the subsequent decade was about 13%. Total
      YPLL was 78% greater among males than among females in 1983 and was nearly twice
      as high in 1994. Premature mortality decreased steadily for non-Hispanic whites,
      from 150,967 to 135,027 years for the years 1983-1994, while increasing 20% among
      blacks (from 179,176 to 215,826 years) and 48% among Hispanics (from 89,869 to
      132,869 years). Among blacks and Hispanics, homicide contributed more years of
      YPLL than did either heart disease or malignant neoplasms in every year of
      observation. The HIV/AIDS epidemic and mortality associated with violence have
      become important public health challenges to the health and well-being of New
      Yorkers.

PMID- 9583715
TI  - Long-term survival of children with human immunodeficiency virus infection in New
      York City: estimates from population-based surveillance data.
AB  - The life expectancy of children with human immunodeficiency virus (HIV) infection
      acquired through mother-to-child transmission has important clinical and public
      health significance. Several sources of population-based surveillance data from
      New York City, covering 1982 through the end of 1994, were combined to estimate
      long-term survival of HIV-infected children and age-specific prevalence. HIV
      incidence among newborns was estimated by applying expected transmission rates to
      seroprevalence surveys of parturient women and by using back-calculation methods.
      HIV prevalence in childhood was based on cumulative HIV incidence and cumulative
      mortality, adjusting for underreporting of death and background causes of death.
      A modified actuarial method was developed to estimate survival of infected
      children. At the beginning of 1995, between 1,945 and 3,323 children less than
      age 13 years were estimated to be living with HIV infection acquired through
      mother-to-child transmission in New York City. Between 36% and 61% of these
      infected children were estimated to survive to age 13 years (median survival, 8.6
      years to >13 years). A substantial proportion of infected children will survive
      to adolescence. Thus, it is important that their educational, medical, and other
      needs be considered. These methods may be useful in other areas in which HIV
      seroprevalence data among childbearing women and HIV mortality statistics are
      available.

PMID- 9583716
TI  - External causes of death among persons with developmental disability: the effect
      of residential placement.
AB  - The authors analyzed death rates from external causes (accidents, injuries,
      homicides, etc.) for persons with developmental disability in California. There
      were 520 such deaths during the 1981-1995 study period, based on 733,705 person
      years of exposure; this represents all persons who received any services from the
      state. Compared with the general California population, persons with
      developmental disability were at lower risk of homicide, suicide, and poisonings
      (standardized mortality ratios, 0.31-0.68), but higher risk of pedestrian
      accidents, falls, fires, and, especially, drowning (standardized mortality
      ratio=6.22). A major focus of the study was comparisons between different
      residential settings. Persons in semi-independent living had significantly higher
      risk than did those in their family home or group homes, with homicides rates
      being three times higher and pedestrian accidents rates being doubled, while
      persons in institutions had much lower risks with respect to most causes. Of the
      28 deaths due to drug and medication overdoses, 79 percent occurred in supported
      living or small-group homes. Avoidable deaths could be reduced by making direct
      care staff more aware of the risks and better trained in acute care, along with
      improved monitoring of special incidents.

PMID- 9583717
TI  - Breastfeeding reduces risk of respiratory illness in infants.
AB  - Breastfeeding has long been believed to protect against infection in infants, but
      protection against respiratory illnesses has not been consistently demonstrated
      in studies in developed countries. Between 1988 and 1992, the authors assessed
      the effect of breastfeeding on incidence and duration of respiratory illnesses
      during the first 6 months of life in a prospective study that actively tracked
      breastfeeding and respiratory illnesses. A cohort of 1,202 healthy infants, born
      in Albuquerque, New Mexico, between January 1, 1988 and June 30, 1990, from homes
      without smokers was enrolled. The daily occurrences of respiratory symptoms and
      breastfeeding status were reported by the mothers every 2 weeks. Illnesses were
      classified as lower respiratory illness (LRI) if wheezing or wet cough was
      reported; the remaining illnesses were classified as upper respiratory. The
      annualized incidence rates for LRI were 2.8, 2.6, and 2.1 during follow-up time
      with no, partial, or full breastfeeding, respectively, but the incidence rates
      for upper respiratory illness and lower respiratory illness combined were similar
      in the three categories. After adjustment for potential confounding factors, full
      breastfeeding was associated with a reduction in lower respiratory illness risk
      (odds ratio=0.81, 95% confidence interval 0.68-0.96). Median duration of all
      respiratory illnesses was 5 days for the fully breastfed infants during the first
      6 months of life compared with a median of 6 days for not breastfed and partially
      breastfed infants. Multivariate analysis confirmed that breastfeeding
      significantly reduced the duration of respiratory illness. This pattern of
      reduced incidence of LRI and shorter duration of all respiratory illnesses
      suggests that breastfeeding reduces the severity of infant respiratory illnesses
      during the first 6 months of life.

PMID- 9583718
TI  - Risk factors for increased bone loss in an elderly population: the Rotterdam
      Study.
AB  - The association of bone loss with age, sex, and several prevalent and modifiable
      potential risk factors for osteoporosis was studied in 1,856 men and 2,452 women
      aged 55 years and over from the Rotterdam Study, a population-based cohort study
      in the Netherlands. The rate of change in femoral neck bone mineral density was
      estimated longitudinally between 1990 and 1995, after 2 years of follow-up on
      average. These rates, adjusted for age and body mass index, were -0.0025 (95%
      confidence interval -0.0038 to -0.0012) in men and -0.0045 (95% confidence
      interval -0.0056 to -0.0034) g/cm2/year in women (p=0.03). Bone loss accelerated
      with age, as seen more clearly in men than in women. Lower body mass index and
      cigarette smoking were associated with increased bone loss in both men and women.
      In men, higher calcium intake was associated with lower rates, and disability was
      associated with borderline significantly higher rates of bone loss (p=0.07). In
      women, a nonsignificant relation was observed with disability, but not with
      dietary calcium intake. Alcohol intake was not consistently related to the rate
      of bone loss in either sex. It is concluded that in elderly people the rate of
      bone loss is higher in women, progresses with age, and is further determined by
      several modifiable risk factors, particularly in men.

PMID- 9583719
TI  - Self-perceived health and 5-year mortality risks among the elderly in Shanghai,
      China.
AB  - Studies of the elderly worldwide over the last 3 decades have reported that a
      self-rating of "poor" compared with "excellent/good" health increases the
      relative risk of dying. The authors tested the strength of this association by
      performing age-stratified Cox regression analyses on a 5-year longitudinal study
      of a representative sample of noninstitutionalized elderly aged 65 years and
      older (n=3,094) in a district of Shanghai, China. More than 20 potential
      confounders that were only partially controlled in other studies and threats to
      response validity due to cognitive impairment or diagnosed dementia that were not
      considered in previous studies were taken into account in this analysis. The
      results showed that among those aged 65-74 years, "poor" perceived health
      increases the adjusted relative risk of death by 1.93 (95% confidence interval
      1.20-3.11) compared with "excellent/good" health. The adjusted relative risk of a
      "fair" rating of health is 2.16 (95% confidence interval 1.44-3.25). In the older
      age group, mortality risks for the ratings of fair as well as poor compared with
      excellent/good health were not statistically significant. The authors posit that
      several mechanisms related to host vulnerability markers and greater-than
      expected utilization of health services may explain the association between self
      assessed health and mortality risks. Future research should strive to develop
      more precise measures of these and related variables.

PMID- 9583720
TI  - Second follow-up of a Dutch cohort occupationally exposed to phenoxy herbicides,
      chlorophenols, and contaminants.
AB  - A retrospective cohort study of workers exposed to phenoxy herbicides,
      chlorophenols, and contaminants (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      other polychlorinated dioxins and furans) has been conducted in a chemical
      factory in the Netherlands. Male workers exposed to phenoxy herbicides or
      chlorophenols showed increased relative risks (adjusted for age, calendar period
      at end of follow-up, and time since first exposure/employment) for total
      mortality (relative risk (RR)=1.8, 95% confidence interval (CI) 1.2-2.5), cancer
      mortality (RR=4.1, 95% CI 1.8-9.0), respiratory cancer (RR=7.5, 95% CI 1.0-56.1),
      non-Hodgkin's lymphoma (RR=1.7, 95% CI 0.2-16.5), and ischemic heart diseases
      (RR=1.8, 95% CI 0.9-3.6) compared with an internal referent group of nonexposed
      workers. By using TCDD levels (predicted at the time of maximum exposure), based
      on extrapolated TCDD levels that were measured in a subset of the cohort,
      estimated relative risks for workers with medium and high TCDD levels were
      comparable with risks derived from the simple and earlier applied dichotomous
      exposure classification. In general, relative risks were highest in the highest
      category, indicating exposure-related increases in risk with TCDD level. In
      conclusion, results of this cohort study support the evidence of a high cancer
      risk in workers exposed to phenoxy herbicides, chlorophenols, and contaminants.

PMID- 9583722
TI  - Disruption of the RB pathway and cell-proliferative activity in non-small-cell
      lung cancers.
AB  - The pathway consisting of retinoblastoma protein (pRB), cyclin D1 and p16 (RB
      pathway) which is involved in the phosphorylation of pRB plays an important role
      in G1/S progression. The disruption of this RB pathway has been reported in
      several types of human neoplasm. An immunohistochemical study of 101 non-small
      cell lung cancers (NSCLCs) showed loss of p16 is in 47 tumors (46.5%) and loss of
      pRB in 42 tumors (41.6%). In 79 of 101 NSCLCs (78.2%), the expression of p16 and
      pRB was complementary (p < 0.0001). Methylation of the cdkn2 gene was detected in
      50% of p16-negative tumors and in 11% of p16-positive tumors. Aberrant expression
      of cyclin D1 was found in 45 tumors (44.5%). The cyclin-D1-positive tumors had
      significantly higher Ki-67 indices than the cyclin-D1-negative tumors
      irrespective of the tumor p16 or pRB expression. Thus, 91 (90%) of 101 NSCLCs
      showed disturbed expression of at least 1 of the 3 components of the RB pathway.
      Our results suggest that the disruption of the RB pathway plays an important role
      in tumorigenesis in NSCLCs and that increased cyclin-D1 expression leads to
      strong proliferative activity which may over-ride the suppressive effect of p16
      and pRB.

PMID- 9583721
TI  - Expression of death-related genes and their relationship to loss of apoptosis in
      T1 ductal breast carcinomas.
AB  - Expression of the death-related proteins (DRPs) Bcl-2, Bax, Bcl-x and Bak that
      regulate cell survival and death was examined using immuno-histochemical methods
      in a group of 142 T1 (<2 cm) ductal breast carcinomas. Immunostaining results
      were correlated with loss of apoptosis and clinicopathological parameters such as
      histological grade (HG) and lymph node involvement. Expression of anti-apoptotic
      proteins Bcl-2 and Bcl-x was found in 57.0% and 62.75% of tumors, respectively.
      Bcl-2 expression, but not Bcl-x expression, was related to loss of apoptosis.
      Expression of the apoptotic proteins Bax and Bak was present in 58% of Bcl-2
      negative tumors and associated significantly with an increase in apoptosis.
      Expression of these DRPs was associated significantly with the HG of the tumors:
      Bcl-2 and Bak expression was predominant in HG I/II tumors, whereas expression of
      Bcl-xL and Bax was commonly observed in HG III tumors, as occurs for p53 over
      expression. Our results suggest that the loss or gain of apoptosis is regulated
      tightly in T1 breast carcinomas through the expression of different effectors
      along with tumor cell differentiation.

PMID- 9583723
TI  - DNA ploidy and cell-cycle analysis in intracranial meningiomas and
      hemangiopericytomas: a study with high-resolution DNA flow cytometry.
AB  - Although various DNA flow-cytometric studies have been performed on meningiomas,
      the role of DNA ploidy and the S-phase fraction (SPF) in predicting biological
      tumor behavior remains unresolved. Discrepant results in earlier studies might be
      due to different preparing, staining and measuring techniques; different quality
      standards; and lack of sophisticated computer software. In this study, high
      resolution DNA flow cytometry using the DNA-specific dye DAPI (4', 6'-diamidino-2
      phenylindol) was performed on stored frozen tissue from 128 microsurgically
      resected meningiomas and 7 hemangiopericytomas, including 17 recurrent
      meningiomas and 4 recurrent hemangiopericytomas. The computer software Multicycle
      2.5 was used to determine the ploidy level and to perform cell-cycle analysis.
      DNA aneuploidy and SPF were significantly higher in atypical, anaplastic and
      recurrent meningiomas and correlated well with histopathological features such as
      focal necrosis, infiltration of dura mater and mitotic activity. Among 128
      meningiomas, 42 had additional DNA aneuploid stem lines. No association between
      hypo- and hyperploidy and either histological subtype or clinical outcome was
      found. In 7 hemangiopericytomas, SPF was significantly higher compared to the
      benign meningioma group, while only 1 tumor was aneuploid. In all 42 DNA
      aneuploid tumors, cell-cycle analysis was performed separately for the euploid
      and aneuploid stem lines. The proliferation parameters (SPF, G2/M phase) were
      significantly higher in the DNA aneuploid stem lines. DNA ploidy and SPF are thus
      useful indicators of different biological behavior within identical histological
      subgroups in meningiomas.

PMID- 9583724
TI  - Expression of folate binding protein as a prognostic factor for response to
      platinum-containing chemotherapy and survival in human ovarian cancer.
AB  - Overexpression of the folate binding protein (FBP) is a common feature in
      epithelial ovarian cancer, but its prognostic significance is not clearly
      understood. We investigated whether FBP in epithelial ovarian cancer specimens is
      a predictor of response to chemotherapy and survival. Between 1990 and 1995, 99
      patients with epithelial ovarian cancer underwent primary surgery and were
      treated with chemotherapeutic regimens including platinum derivatives. First-line
      chemotherapy was performed in 58 patients with residual disease and in 41
      patients without residual disease after primary laparotomy. FBP expression level
      was determined in frozen specimens by cyto-fluorimetric assay using the MOv 18
      monoclonal antibody (MAb). Association of FBP fluorescence index (FI) with
      clinical characteristics, response to chemotherapy, and survival was studied by
      univariate and multivariate analysis. In the 58 patients with residual disease
      after primary surgery, failure to respond to chemotherapy (complete or partial
      remission) was about 15-fold higher (95% confidence interval, 2.96-77.43) when
      tumors had FBP FI above the median value (FBP FI = 3.25). FBP FI was not a
      predictor of survival in the entire series of tumors (99 patients). However, in
      the subgroup of 58 patients with residual disease after primary surgery, survival
      analysis confirmed the disadvantage observed with respect to response to
      chemotherapy in patients expressing FBP FI above the median value (hazard ratio
      2.01; 95% confidence interval 0.95-4.24). In conclusion, higher levels of FBP
      expression might be a predictor of chemotherapy response failure in ovarian
      cancer. In patients with residual disease after primary surgery, FBP FI could
      represent a valuable prognostic marker for survival.

PMID- 9583725
TI  - Co-expression of osteopontin and CD44v9 in gastric cancer.
AB  - We have examined the expression of osteopontin (OPN) in 40 human primary gastric
      carcinoma tissues, 5 metastatic foci (lymph nodes) and corresponding normal
      mucosas. Twenty-nine of 40 primary tumors (72.5%) and 3 of 5 lymph node
      metastases (60%) overexpressed OPN mRNA in comparison with those of the
      corresponding normal mucosa. The incidence as well as relative expression level
      of OPN mRNA was higher in well differentiated gastric cancers than poorly
      differentiated ones. Moreover, increased OPN mRNA expression in primary tumor
      specimens was observed along with the advancement of the clinico-pathological
      stage. Using in situ hybridization (ISH) analysis, not only inflammatory cells in
      tumor stroma but also tumor cells showed positive signals for OPN mRNA. By
      immunohistochemistry, co-immunoreaction of OPN and CD44v9 in tumor cells
      obviously correlated with the degree of lymphatic vessel invasion or long distant
      lymph node metastases in poorly differentiated gastric cancer. Interestingly,
      strong co-immunoreaction of OPN and CD44v9 of tumor cells was concommitant with
      cluster formation in the lymphatic vessels. Our results suggest that
      overexpression of OPN correlated with the progression of human gastric carcinoma.
      Especially in CD44-bearing poorly differentiated gastric cancer, interaction
      between OPN and CD44 may parallel lymphogenous metastasis.

PMID- 9583726
TI  - Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and
      MUC2 with the histopathological subtype and prognosis of gastric carcinomas.
AB  - The expression of MUC1 and MUC2 mucin peptide core antigens in gastric carcinomas
      was studied by immunohistochemistry to determine correlations with TNM stage and
      histo-pathological classifications as well as a possible prognostic impact.
      Paraffin-embedded specimens from 128 gastric carcinomas with a minimal follow-up
      of 5 years were immunostained. In addition to a polyclonal antiserum generated
      against polymorphic epithelial mucin (MUC1) from human milk, 2 monoclonal
      antibodies (MAbs), HMFG2 (anti-MUC1) and 4FI (anti-MUC2), were applied.
      Reactivity of carcinomas was correlated with the classifications of the UICC
      (TNM), WHO and Lauren. Correlations with overall survival were analyzed using the
      Kaplan and Meier product limit method. MUC1 immunoreactivity was associated with
      an advanced pTNM stage. The demonstration of both mucin species (MUC1, MUC2)
      displayed a statistically significant correlation with tubular/papillary vs.
      signet-ring cell differentiation as well as with intestinal-type vs. diffuse-type
      of tumor growth according to Lauren. In particular, MUC2 was only rarely
      detectable in signet-ring cell and diffuse-type tumors. MUC1 correlated with poor
      prognosis in all cases and the subgroup of stage I tumors. According to the
      histopathological classifications, a similar result was observed in signet-ring
      cell and diffuse-type carcinomas. In contrast, MUC2 reactivity was associated
      with a favourable prognosis of intestinal-type carcinomas. In the non-neoplastic
      gastric mucosa, both peptide cores were recognized in the superficial epithelium,
      whereas parietal cells contained only MUC1, and intestinal metaplasia almost
      exclusively MUC2 antigens. We conclude that the mucin peptide core antigens are
      suitable markers for the tubule-rich gastric carcinomas, which may in part be
      derived from intestinal metaplasia. In addition, MUC1 may exert a prognostic
      relevance and appears to be involved in the progression of diffuse-type tumors.

PMID- 9583727
TI  - Reduced vascular basement-membrane immunostaining in mucinous tumours of the
      ovary.
AB  - Tumour vasculature is heterogeneous, exhibiting a range of vessel densities and
      the vascular basement membrane (VBM) of tumour blood vessels may be fragmented or
      absent. Increased microvessel density (MVD) has been reported in mucinous ovarian
      tumours as compared with other histologic sub-types. We hypothesized that VBM
      immunostaining differs between regions of the ovarian tumour vasculature and
      between ovarian tumour types exhibiting different MVD. Serial sections from 56
      ovarian tumours were immunostained using antibodies to the VBM components
      collagen IV, heparan sulphate proteoglycan and laminin, and the endothelial cell
      marker CD31. Regions of high and average MVD were selected, and the number of
      vessels positive for each VBM component were counted and expressed as a
      percentage of the number of CD31-positive vessels. The percentage of VBM-positive
      vessels did not differ between the high and average MVD regions of borderline or
      malignant, mucinous and serous tumours. The percentage of VBM-positive vessels in
      mucinous tumours was less than that observed in malignant and borderline serous
      tumours and benign tumours (p < 0.02). Possible explanations for these findings
      are (i) that VBM turnover is similar throughout the vasculature; (ii) that the
      VBM is present both during angiogenesis and in the newly formed vessels of high
      MVD regions; or (iii) that an alternative angiogenesis mechanism is utilized in
      different ovarian tumour types, or even between different regions of the same
      tumour.

PMID- 9583728
TI  - High pre-treatment serum level of vascular endothelial growth factor (VEGF) is
      associated with poor outcome in small-cell lung cancer.
AB  - Vascular endothelial growth factor (VEGF) is an important regulator of
      angiogenesis and vascular permeability. Increased serum VEGF concentrations (S
      VEGF) have been found in patients with various types of human cancer, including
      cancer of the lung. However, the clinical and prognostic significance of S-VEGF
      in cancer is unknown. We measured S-VEGF, using enzyme-linked immunosorbent
      assay, in sera taken from 68 untreated patients with small-cell lung cancer
      (SCLC) at the time of diagnosis. The patients were treated with 6 cycles of
      cisplatin and etoposide, and were randomly assigned to receive recombinant
      interferon, leukocyte interferon or neither. S-VEGF ranged from 70 to 1738 pg/ml
      (mean, 527 pg/ml). The patients who achieved partial or complete response to
      treatment had lower pre-treatment S-VEGF than the non-responding patients (p =
      0.0083, Mann-Whitney test). High (>527 pg/ml) S-VEGF was associated with poor
      survival (p = 0.012, Log Rank Test), and all 3-year survivors had lower than mean
      pre-treatment S-VEGF. In a multivariate analysis, S-VEGF and stage were the only
      independent prognostic factors, and the estimated 3-year survival of the patients
      with limited stage disease and low pretreatment S-VEGF (n = 17, 25% of all
      patients) was 41% (p = 0.0055, log rank test). These data show that high
      pretreatment S-VEGF is associated with poor response to treatment and
      unfavourable survival in patients with SCLC treated with combination chemotherapy
      with or without interferon.

PMID- 9583729
TI  - Immunofluorometrically determined p53 accumulation as a prognostic indicator in
      Italian breast cancer patients.
AB  - The prognostic value of p53 protein accumulation in breast cancer, especially as
      detected by methods other than immunohistochemistry, has not been established
      unequivocally. A sensitive immunofluorometric assay of p53 protein employing DO-1
      and CM-1 antibodies was used in this study to assay extracts of 171 breast
      carcinomas from northern Italy. p53 over-expression, demonstrated in 36 (21%)
      tumours, was associated with lack of oestrogen receptor (ER) expression but was
      not related to patient age, stage, lymph node status, tumour size, histologic
      type, grade or progesterone receptor (PR) expression status in contingency
      tables. An increased risk for cancer relapse of p53-positive patients compared to
      p53-negative patients was determined using multivariate Cox regression analysis,
      which also showed that p53 protein over-expression was an independent predictor
      of reduced disease-free survival in node-positive and ER+ patients but not in
      node-negative or ER- individuals. The equivalent analysis for assessing the
      impact of p53 status on overall survival was not statistically significant,
      possibly reflecting the short patient follow-up. Our results suggest that an
      immunoassay of p53 protein, applicable to cytosolic extracts prepared for steroid
      hormone receptor analyses, may provide information for breast cancer prognosis.

PMID- 9583730
TI  - Bcl-2 expression and prognosis of patients with endometrial carcinoma.
AB  - Bcl-2 protein inhibits apoptosis, reduces the requirement for growth factors, and
      thereby extends the survival of cells. Recent findings of Bcl-2 in several solid
      tumors suggest that it might contribute to the genesis of some types of cancer.
      Over-expression of Bcl-2 might play a role in carcinogenesis and malignant
      progression of endometrial carcinoma. The aims of this study were to determine
      Bcl-2 expression in endometrial carcinoma in relation to other histopathologic
      prognostic factors, and to test its prognostic significance in patients with
      endometrial carcinoma. A total of 61 endometrioid-type endometrial carcinomas
      were immunohistochemically investigated for Bcl-2 expression on cryostat
      sections. Bcl-2 localization was observed in cytoplasm in 18 tumors, in nucleus
      in 27 tumors, or in both in 5 tumors. In 11 tumors, Bcl-2 was observed neither in
      cytoplasm nor in nucleus. There was not a statistically significant relationship
      between grade of tumor and Bcl-2 expression. Cytoplasmic Bcl-2 became less
      frequently expressed as the tumor invaded the myometrium deeper (p < 0.025).
      Retroperitoneal lymph-node dissection was performed in 57 patients. Multiple
      regression analysis showed that lymph-vascular space invasion and nuclear
      expression of Bcl-2 were correlated to pelvic lymph-node metastasis (p < 0.0001
      and < 0.05 respectively). Univariate Cox regression analysis revealed that
      nuclear Bcl-2 expression was associated with shorter survival (p < 0.05) than
      that of patients with cytoplasmic Bcl-2 expression. Pelvic node metastasis was a
      significant prognostic factor for patients who underwent systematic
      retroperitoneal lymph-node dissection. Cox multivariate-regression analysis
      revealed that pelvic node metastasis and cervical invasion were the most
      important prognostic factors in this series of patients. When the analysis was
      made after exclusion of pelvic node metastasis, histologic grade (hazard ratio =
      2.4), cervical invasion (hazard ratio = 3.7) and nuclear Bcl-2 expression (hazard
      ratio = 11.5) were shown to be significant predictors of survival of the
      patients. These results indicate that aberrant Bcl-2 expression might be involved
      in malignant progression of endometrioid-type endometrial carcinoma. Site of Bcl
      2 localization may be an important predictor of prognosis for patients with
      endometrioid-type endometrial carcinoma.

PMID- 9583731
TI  - Genetic sub-types of human malignant astrocytoma correlate with survival.
AB  - In human malignant astrocytoma, age of the patient and histological grade of the
      tumor are important prognostic variables. Several genetic changes have been
      reported to occur in these tumors, which may be of additional and independent
      prognostic relevance. To determine their prognostic significance, we analyzed 75
      high-grade tumors, 12 anaplastic astrocytomas and 63 glioblastomas multiforme,
      for the presence of genetic changes that occur frequently in high-grade
      astrocytoma, i.e., loss of heterozygosity (LOH) for chromosome 10, p53-gene
      alteration (mutation and/or LOH), and EGFR-gene amplification. We defined 4
      groups of patients who showed a specific combination of genetic changes in the
      tumor: group 1, p53-gene alteration without complete LOH 10; group 2, complete
      LOH 10 only; group 3, p53-gene alteration + complete LOH 10; group 4, complete
      LOH 10 + EGFR-gene amplification. In univariate analysis, the log-rank test
      revealed significant differences in survival between patients of group 1 (median
      survival of 13 months) and group 3 (median survival of 5.2 months, p = 0.0058)
      and between patients of group 1 and group 4 (median survival of 4 months, p =
      0.0033). In multivariate analysis, age and genetic sub-type proved to be
      important prognostic variables, whereas histological grading was less important.
      The age-corrected survival time for group-4 patients is significantly shorter
      than that for group-1 patients (relative risk = 3.79, p = 0.0075). Our data
      indicate that genetic sub-type is an important prognostic variable in human high
      grade astrocytoma.

PMID- 9583732
TI  - Survival and prognostic factors of endometrial cancer patients in Iceland 1964
      1985: can attendance at population-based Pap-smear screening affect survival?
AB  - After histological review of all cases registered during the period 1964-1985 at
      the Cancer Registry, 260 cases with endometrial carcinoma were eligible for
      analyses of survival rates and prognostic factors, as well as the association of
      Pap-smear screening attendance with these factors and survival. The total age
      adjusted 5- and 10-year relative survival rates were 76% and 75%, respectively.
      The prognostic factors were tested by univariate analysis and simultaneously by a
      multivariate analysis using the Cox proportional hazards model. Factors that
      independently gave a less favorable prognosis were non-attendance at screening,
      older age at diagnosis, deep myometrial invasion, advancing stages and tumor
      grading, radiotherapy only, extra-genital symptoms and histology types of serous,
      clear cell and undifferentiated tumors (histologic type 3). Tested simultaneously
      with the Cox proportional hazards model, parameters that maintained a less
      favourable prognosis were grade 3, stage III-IV, deep myometrial invasion, older
      age, radiotherapy only and extra-genital symptoms. In addition, screening
      attendance showed significant interaction with age. In stages III and IV only
      grade 3 maintained a significantly less favorable prognosis. We conclude that our
      results indicate that attendance at Pap-smear screening (taking Pap smears and
      screening for genital symptoms) has a favorable prognostic value, especially
      among women under the age of 62.

PMID- 9583733
TI  - Identification of cystatin B in human esophageal carcinoma, using differential
      displays in which the gene expression is related to lymph-node metastasis.
AB  - Identification of the genes that are specifically expressed in either tumor or
      normal tissue is important for understanding cancer biology. Using differential
      displays, we obtained one gene which was specifically expressed in normal tissue
      but is only rarely expressed in carcinoma tissue of the human esophagus. The
      sequence of this gene was identical with cystatin B, known to be one of the
      cysteine-proteinase inhibitors, mainly inhibiting cathepsin L. There is little
      information on the clinical significance of cystatin B expression in human
      esophageal carcinoma. We thus studied the mRNA expression of cystatin B in 45
      tumor/normal pair specimens of the esophagus, using the semi-quantitative reverse
      transcriptase polymerase chain reaction technique. The expression of cystatin B
      in tumor tissue was found to be markedly decreased compared with that of the
      corresponding normal tissue. The cases with a tumor/normal ratio of less than 0.5
      showed high frequency of lymph-node metastasis and more advanced clinical stage
      as compared with those whose tumor/normal ratio was equal to or more than 0.5.
      The decreased expression of cystatin B protein in carcinoma tissue was confirmed
      by immunohistochemical staining. Our study suggests that reduced expression of
      cystatin B in esophageal-carcinoma tissue is associated with lymph-node
      metastasis and may therefore prove to be a useful marker for predicting the
      biologic aggressiveness of human esophageal carcinoma.

PMID- 9583734
TI  - Involvement of vascular endothelial growth factor and urokinase-type plasminogen
      activator receptor in microvessel invasion in human colorectal cancers.
AB  - To evaluate the association among known angiogenic growth factors or factors
      related to the plasminogen activation system and clinicopathological factors in
      patients with colorectal cancer, we examined the expression of vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
      transforming growth factor-alpha (TGF-alpha), urokinase-type plasminogen
      activator (u-PA), u-PA receptor (u-PA-R) and plasminogen activator inhibitor-1
      (PAI-1) in clinical specimens of colorectal cancers by Northern blot analysis. In
      comparison with the expression of these angiogenesis-related genes in 7 paired
      samples of colorectal cancers and the adjacent normal mucosa, VEGF mRNA level was
      significantly higher in the cancer tissues than in the adjacent normal mucosa (p
      < 0.05). We analyzed expression of these genes in 44 cases of primary colorectal
      cancers. Among the 3 angiogenic growth factors we examined, VEGF mRNA expression
      was significantly higher in the cancer tissues with blood vessel invasion or with
      lymphatic vessel invasion than in those without, respectively (p < 0.05). On the
      other hand, u-PA-R mRNA expression was significantly higher in the cancers with
      blood vessel invasion than in those without (p < 0.05). In addition, there was a
      correlation between the expression levels of VEGF and u-PA-R mRNA in the cancer
      tissues we have examined. Using immunohistochemistry, strong staining of VEGF or
      u-PA-R was observed in the cancer cells invading the microvessels. Our findings
      suggest that malignant transformation might accompany the upregulation of VEGF
      expression in colorectal cancers and that VEGF and u-PA-R might contribute
      cooperatively to increase angiogenesis around the tumor as well as the metastasis
      via microvessels.

PMID- 9583735
TI  - Expression and tissue localization of matrix metalloproteinase 7 (matrilysin) in
      human gastric carcinomas. Implications for vessel invasion and metastasis.
AB  - We examined the production and tissue localization of matrix metalloproteinase-7
      (MMP-7 = matrilysin) in human gastric carcinomas and analyzed the data in
      connection with the clinicopathological factors. Sandwich-enzyme immunoassay for
      the zymogen of MMP-7 (proMMP-7) showed enhanced production of MMP-7 in carcinoma
      tissues compared with control normal gastric mucosa. Immunohistochemical studies
      demonstrated that MMP-7 is localized predominantly to the carcinoma cells in 71%
      of the carcinoma samples (30/42 cases). The percentage of immunoreactive
      carcinoma cells to total carcinoma cells (positive ratio) was significantly
      higher in intestinal-type carcinomas (26%, median) than in diffuse-type
      carcinomas (3%, median) (p < 0.05). The positive ratio was markedly higher in
      carcinoma groups with vascular invasion (28%) or lymphatic permeation (12%) than
      in those without invasion (6%) or permeation (0%) (p < 0.05). It was also
      significantly higher in carcinoma groups with liver (49%) or lymph-node
      metastases (15%) than in those without metastases (6 and 2% respectively) (p <
      0.05). Both proMMP-7 of 28 kDa and active MMP-7 of 19 kDa were detected in the
      carcinoma tissues by immunoblotting. Reverse-transcription-PCR showed specific
      amplification in 50% of the carcinoma cases (6/12 cases) and 8% of the normal
      control specimens (1/12 cases). In situ hybridization demonstrated that the
      carcinoma cells almost selectively express MMP-7 mRNA. These data suggest that
      enhanced production of proMMP-7 and its activation are implicated in invasion and
      metastasis of human gastric carcinomas.

PMID- 9583736
TI  - Discordant expression of mRNA and protein for urokinase and tissue plasminogen
      activators (u-PA, t-PA) in endometrial carcinoma.
AB  - Tissue samples were obtained from normal (n = 92), hyperplastic (n = 22) and
      malignant (n = 35) endometria. Urokinase and tissue plasminogen activators (u-PA,
      t-PA) were assayed in acetate detergent buffer extracts and their mRNAs
      quantitated in autoradiograms of Northern blots. The tissue content of u-PA was
      significantly higher in adenocarcinomas compared to normal and hyperplastic
      endometria. Tumors with poor differentiation and extensive myometrial invasion
      had the highest levels. The content of t-PA was increased in hyperplastic
      endometria but not in adenocarcinomas. The tissue content of t-PA was inversely
      related to clinical stage and loss of differentiation in malignant tumors. In
      contrast to the protein data, u-PA mRNA was not higher and t-PA mRNA was much
      lower in malignant compared to benign tumors. Thus, high tumor tissue content of
      u-PA does not result from transcriptional regulation, and reduction of t-PA mRNA
      may indicate down-regulation of transcription or possibly reduced mRNA stability.
      Furthermore, the discrepancy between protein and mRNA for both activators
      probably indicates up-regulation of the translation process since decreased
      degradation of activator proteins is a less likely explanation.

PMID- 9583737
TI  - Cellular expression of growth hormone and prolactin receptors in human breast
      disorders.
AB  - Growth hormone (GH) and prolactin (PRL) exert their regulatory functions in the
      mammary gland by acting on specific receptors. Using isotopic in situ
      hybridization and immunohistochemistry, we have localized the expression of hGH
      receptor (hGHR) and hPRL receptor (hPRLR) in a panel of human breast disorders.
      Surgical specimens from adult females included normal breast, inflammatory
      lesions (mastitis) benign proliferative breast disease (fibroadenoma, papilloma,
      adenosis, epitheliosis), intraductal carcinoma or lobular carcinoma in situ, and
      invasive ductal, lobular or medullary carcinoma. Cases of male breast enlargement
      (gynecomastia) were also studied. In situ hybridization analysis demonstrated the
      co-expression of hGHR and hPRLR mRNA in all samples tested. Epithelial cells of
      both normal and tumor tissues were labelled. Quantitative estimation of receptor
      mRNA levels was regionally measured in areas corresponding to tumor cells and
      adipose cells from the same section. It demonstrated large individual variation
      and no correlation emerged according to the histological type of lesion. Receptor
      immunoreactivity was detected both in the cytoplasm and nuclei or in the
      cytoplasm alone. Scattered stromal cells were found positive in some cases, but
      the labeling intensity was always weaker than for neoplastic epithelial cells.
      Our results demonstrate the expression of the hGHR and hPRLR genes and their
      translation in epithelial cells of normal, proliferative and neoplastic lesions
      of the breast. They also demonstrate that stromal components express GHR and PRLR
      genes. Thus the putative role of hGH or hPRL in the progression of proliferative
      mammary disorders is not due to grossly altered levels of receptor expression.

PMID- 9583738
TI  - Adhesion molecules and microvascular changes in the nonobese diabetic (NOD) mouse
      pancreas. An NO-inhibitor (L-NAME) is unable to block adhesion inflammation
      induced activation.
AB  - The aim of the present study was to investigate the immunoreactivity of
      pancreatic microvasculature with emphasis on the adhesion molecule expression in
      NOD mice at a very early stage and after the start of infiltration, before the
      onset of the diabetic disease. Immunoreactivity for Ia-b, BM8 (mouse macrophages)
      and inter-cellular-adhesion-molecule-1 (ICAM-1) molecules in untreated control
      mice and in animals treated using an inhibitor of nitric oxide (NO) formation (L
      arginine analogue), as well as islet culture, nitrite assay and ultrastructural
      studies were performed. Results showed that Ia-b and ICAM-1 immunoreactivities on
      endothelia are a very early phenomenon and that pancreatic blood vessels and, in
      particular, some peri-islet venules, as well as several venules of the exocrine
      parenchyma, undergo significant morphological changes. Several endothelial cells
      of both peri-islet and extra-islet compartments, often showed Ia-b and ICAM-1
      immunoreactivities, demonstrating that these cells are important for the adhesion
      processes taking place during early autoimmune inflammation. Inhibition of NO
      formation does not significantly affect ICAM-1 and Ia-b immunoreactivity both in
      vivo and in vitro, BM8 immunoreactive cells were considerably less in number
      although these were detected either around islets or along pancreatic septa, but
      rarely within the epithelial layer.

PMID- 9583739
TI  - T cell responses in EAMG-susceptible and non-susceptible mouse strains after
      immunization with overlapping peptides encompassing the extracellular part of
      Torpedo californica acetylcholine receptor alpha chain. Implication to role in
      myasthenia gravis of autoimmune T-cell responses against receptor degradation
      products.
AB  - To study the role in myasthenia gravis (MG) of peptides resulting from
      acetylcholine receptor (AChR) degradation, we examined the ability of AChR
      peptides to induce T cell responses that are capable of cross-reacting with
      intact AChR. The studies were carried out in an experimental autoimmune MG (EAMG)
      susceptible mouse strain [C57BL/6 (B6)] as well as in two non-susceptible strains
      [B6.C-H-2bm12 (bm12) and C3H/He]. A set of overlapping peptides encompassing the
      extracellular part (residues 1-210) of the alpha-chain of Torpedo californica (t)
      AChR were used, individually or in equimolar mixtures, as immunogens. In B6,
      immunization with peptides alpha45-60, alpha111-126, alpha146-162 and alpha182
      198 gave T cells that responded in vitro to the correlate immunizing peptide.
      Only the T cells against the latter three peptides cross-reacted with tAChR.
      Peptide alpha146-162 exhibited the highest in vitro reaction with the immunizing
      peptide and cross-reaction with tAChR. T cells obtained by immunization of B6
      with an equimolar mixture of the peptides responded in vitro to peptides alpha111
      126, alpha146-162 and alpha182-198 and cross-reacted very strongly with tAChR. In
      bm12 and C3H/He, a number of peptides evoked, when used individually as
      immunogens, strong or moderate T cell responses that recognized in vitro the
      correlate immunizing peptide but cross-reacted poorly with tAChR. Immunization
      with the mixture of the peptides gave T cells that recognized several peptides in
      each strain butdid not cross-react with alpha146-162 or tAChR. The results
      indicate that the ability to recognize alpha146-162 or AChR by T cells against
      peptides resulting from receptor degradation can account for the susceptibility
      to, and aggravation of, MG in B6.

PMID- 9583741
TI  - Natural cryptic autoantibodies.

PMID- 9583740
TI  - T cells infiltrating the skin of Tsk2 scleroderma-like mice exhibit T cell
      receptor bias.
AB  - The T cell repertoire expressed by Tsk2 mice, a novel experimental model of
      systemic sclerosis, was examined to determine whether cells infiltrating the
      areas of involved skin exhibit a T cell receptor (TCR) bias. Reverse
      transcription-polymerase chain reactions (RT-PCR) were conducted using RNA
      extracted from lymph nodes and skin from TSk2 mice and from normal mice, with an
      oligonucleotide primer library specific for the variable region of the TCR (beta)
      chain. RT-PCR signals were observed in all lymph node cell (LNC) samples from
      both Tsk2 mice and control mice, with eighteen of the twenty-one Vbeta types
      present. In contrast, cDNA extracted from areas of involved skin from Tsk2 mice
      exhibited a restricted pattern, with positive Vbeta signals corresponding to
      eight T cell subtypes (Vbeta1, 6, 8.1, 8.2, 10, 11, 16, and 18). Band strength
      analysis revealed that three Vbeta subtypes dominated within this restricted
      pattern (Vbeta8.1, 11, and 18). Moreover, this pattern of Vbeta bias was
      consistent among the four skin samples from different Tsk2 mice. These data
      suggest that a restricted T cell population participates in the inflammatory cell
      infiltrate of Tsk2 skin.

PMID- 9583742
TI  - Cellular and molecular mechanisms for the initiation and progression of beta cell
      destruction resulting from the collaboration between macrophages and T cells.
AB  - Insulin-dependent diabetes mellitus (IDDM) is caused by the progressive
      autoimmune destruction of insulin-producing pancreatic beta cells. Although the
      pathogenesis of autoimmune IDDM has been extensively studied, the precise
      mechanisms involved in the initiation and progression of beta cell destruction
      remain unclear. Animal models used in the study of IDDM, such as the BioBreeding
      (BB) rat and the nonobese diabetic (NOD) mouse, have greatly enhanced our
      understanding of the pathogenic mechanisms involved in this disease. In these
      animals, macrophages and/or dendritic cells are the first cell types to
      infiltrate the pancreatic islets. Macrophages must be involved in the
      pathogenesis of IDDM early on, since inactivation of macrophages results in the
      near-complete prevention of insulitis and diabetes in both NOD mice and BB rats.
      The presentation of beta cell-specific autoantigens by macrophages and/or
      dendritic cells to CD4+ T helper cells, in association with MHC class II
      molecules, is considered the initial step in the development of autoimmune IDDM.
      The activated macrophages secrete IL-12, which stimulates Th1 type CD4+ T cells.
      The CD4+ T cells secrete IFN-gamma and IL-2. IFN-gamma activates other resting
      macrophages, which, in turn, release cytokines, such as IL-1beta, TNF-alpha, and
      free radicals, which are toxic to beta cells. During this process, IL-2 and other
      cytokines induce the migration of CD8+ peripheral T cells to the inflamed islets,
      perhaps by inducing the expression of a specific homing receptor. The
      precytotoxic CD8+ T cells that bear beta cell-specific autoantigen receptors
      differentiate into cytotoxic effector T cells upon recognition of the beta cell
      specific peptide bound to MHC class I molecules in the presence of beta cell
      specific CD4+ T helper cells. The cytotoxic CD8+ T cells then effect beta cell
      damage by releasing perforin and granzyme, and by Fas-mediated apoptosis. In this
      way, macrophages, CD4+ T cells, and CD8+ T cells synergistically destroy beta
      cells, resulting in the onset of autoimmune IDDM.

PMID- 9583743
TI  - Disturbed systemic immune balance in periodontal disease.

PMID- 9583745
TI  - Preimplantation genetic diagnosis of severe inherited skin diseases.
AB  - Considerable progress has been made recently in elucidating the molecular
      pathology underlying several forms of inherited skin diseases. One of the most
      immediate benefits of these discoveries has been the development of DNA-based
      prenatal diagnosis in pregnancies at risk for recurrence of a particular
      disorder. In less than 2 decades, prenatal testing has progressed from mid
      trimester fetal skin biopsies or protein analysis in a limited number of
      conditions to first trimester chorionic villus sampling in a much broader range
      of genodermatoses. Advances in in vitro fertilization protocols and embryo
      manipulation technology have further led to the feasibility of even earlier
      prenatal diagnosis through preimplantation genetic diagnosis. This article
      details some of the recent advances in genetic skin disease research relevant to
      prenatal diagnosis and explores the possibilities and practicalities of
      preimplantation genetic diagnosis in the prevention of these conditions.

PMID- 9583744
TI  - Hemidesmosomal variants of epidermolysis bullosa. Mutations in the alpha6beta4
      integrin and the 180-kD bullous pemphigoid antigen/type XVII collagen genes.
AB  - Epidermolysis bullosa (EB), a heterogeneous group of genodermatoses, is
      characterized by fragility and blistering of the skin, associated with
      characteristic extracutaneous manifestations. Based on clinical severity,
      constellation of the phenotypic manifestations, and the level of tissue
      separation within the cutaneous basement membrane zone, EB has been divided into
      distinct subcategories. Traditionally, these include the simplex, junctional and
      dystrophic variants of EB. Recent attention has been drawn to variants of EB
      demonstrating tissue separation at the level of hemidesmosomes, ultrastructurally
      recognizable adhesion complexes within the cutaneous basement membrane zone.
      Clinically, these hemidesmosomal variants manifest either as generalized atrophic
      benign epidermolysis bullosa (GABEB), EB with pyloric atresia, or EB with late
      onset muscular dystrophy. Elucidation of basement membrane zone components by
      molecular cloning and development of mutation detection strategies have revealed
      that the hemidesmosomal variants of EB result from mutations in the genes
      encoding the subunit polypeptides of the 180-kD bullous pemphigoid antigen/type
      XVII collagen, the alpha6beta4 integrin, or plectin, respectively. Collectively,
      these data add to the understanding of the molecular complexity of the cutaneous
      basement membrane zone in EB, as attested by the fact that mutations in 10
      different genes can underlie different variants of EB. Elucidation of mutations
      in different forms of EB has direct application to genetic counseling and DNA
      based prenatal testing in families with EB.

PMID- 9583746
TI  - Neuropeptides and Langerhans cells.
AB  - The immune system and nervous system are intimately related. In addition to
      neuroendocrine mechanisms, neuropeptides have a variety of effects on immune
      cells and are responsible at least in part for neurogenic inflammation. The
      presence of neuropeptides in the skin has been well documented. The influence of
      neuropeptides on Langerhans cells is the focus of this paper. The physical
      presence and effects of calcitonin gene-related peptide on Langerhans cells is
      emphasized. Discussion also includes the putative inflammatory and immunologic
      roles of vasoactive intestinal peptide, substance P, neurotensin, neuropeptide Y,
      and somatostatin in the skin.

PMID- 9583747
TI  - Neuropeptides in the skin: interactions between the neuroendocrine and the skin
      immune systems.
AB  - The interaction between components of the nervous system and multiple target
      cells in the cutaneous immune system has been receiving increasing attention. It
      has been observed that certain skin diseases such as psoriasis and atopic
      dermatitis have a neurogenic component. Neuropeptides released by sensory nerves
      that innervate the skin and often contact epidermal and dermal cells can directly
      modulate functions of keratinocytes, Langerhans cells (LC), mast cells, dermal
      microvascular endothelial cells and infiltrating immune cells. Among these
      neuropeptides the tachykinins substance P (SP) and neurokinin A (NKA), calcitonin
      gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin
      (SOM) have been reported to effectively modulate skin and immune cell functions
      such as cell proliferation, cytokine production or antigen presentation under
      physiological or pathophysiological conditions. Expression and regulation of
      their corresponding receptors that are expressed on a variety of skin cells as
      well as the presence of neuropeptide-specific peptidases such as neutral
      endopeptidase (NEP) or angiotensin-converting enzyme (ACE) determine the final
      biological response mediated by these peptides on the target cell or tissue.
      Likewise, skin cells like keratinocytes or fibroblasts are a source for
      neurotrophins such as nerve growth factor that are required not only for survival
      and regeneration of sensory neurons but also to control responsiveness of these
      neurons to external stimuli. Therefore, neuropeptides, neuropeptide receptors,
      neuropeptide-degrading enzymes and neurotrophins participate in a complex,
      interdependent network of mediators that modulate skin inflammation, wound
      healing and the skin immune system. This review will focus on recent studies
      demonstrating the role of tachykinins, CGRP, SOM and VIP and their receptors and
      neuropeptide-degrading enzymes in mediating neurogenic inflammation in the skin.

PMID- 9583748
TI  - What exactly is "atopy"?

PMID- 9583751
TI  - The socioeconomic impact of chronic back pain: is anyone benefiting?

PMID- 9583749
TI  - Molecular basis of non-lethal junctional epidermolysis bullosa: identification of
      a 38 basepair insertion and a splice site mutation in exon 14 of the LAMB3 gene.
AB  - Epidermolysis bullosa (EB) is a group of genodermatoses characterized by
      fragility and easy blistering of the skin. In the junctional forms of EB (JEB),
      blisters occur at the level of the lamina lucida, and specific mutations have
      been detected in the genes encoding different components of the hemidesmosomal
      anchoring filament complex. In the non-lethal form of JEB (NL-JEB), mutations in
      genes encoding two of the polypeptide chains of the anchoring filament protein
      laminin 5 have recently been described. In this study, we searched for mutations
      in a family using PCR amplification of exon 14 of LAMB3, the laminin 5 beta3
      chain gene, followed by heteroduplex analysis and automated sequencing of the PCR
      products. We detected a novel combination of mutations in this family, consisting
      of an out-of frame insertion on one allele, and a splice site mutation on the
      other allele, representing the first report of a large insertion in LAMB3,
      together with a splice site mutation inherited in trans, which result in the NL
      JEB phenotype.

PMID- 9583750
TI  - Decreased frequency of interferon-gamma-producing CD4+ cells in the peripheral
      blood of patients with atopic dermatitis.
AB  - Recently, decreased interferon-gamma (IFN-gamma) and increased interleukin (IL)-4
      production have been reported in measurements of the content of the cytokines in
      culture supernatants of peripheral blood mononuclear cells (PBMC) obtained from
      patients with atopic dermatitis (AD). These data suggest deviation of PBMC into
      Th2-reactive cells in AD. In the present study, we examined the frequency of IL-2
      , IL-4-, and IFN-gamma-producing cells in PBMC with flow cytometry. PBMC from 16
      patients with AD and 18 healthy controls were stimulated for 2 days with anti-CD3
      and IL-2, and further cultured for 4 days with a maintenance dose of IL-2.
      Thereafter these cells were restimulated with phorbol 12-myristate 13-acetate
      (PMA) and ionomycin for 4 h in the presence of monensin. After fixation of the
      cells, the cell membranes were made permeable and intracellular cytokines were
      stained with anti-IL-2, anti-IL-4 or anti-IFN-gamma antibody. Cytokine-producing
      cells were analyzed by gating CD4+- or CD8+-subsets. Thus counted frequency of
      IFN-gamma-producing cells was significantly decreased in CD4+ subsets of AD
      patients (9.9+/-7.4%) when compared with that in the controls (20.0+/-6.7%).
      There was no significant difference either in the frequency of IL-2- or IL-4
      producing CD4+ subsets or in that of CD8+ subsets. Furthermore, in the enzyme
      linked immunosorbent assay, we also found a decreased production of IFN-gamma in
      the culture of PBMC from AD patients, when compared with those from healthy
      controls, although it was only at a marginally significant level (P=0.07). Again
      there was no increase in IL-4 concentration in AD patients. In addition, we found
      a weak negative relationship between the disease severity and the frequency of
      these cells. These results suggest that the decreased frequency of IFN-gamma
      producing CD4+ cells with subsequently decreased production of IFN-gamma play a
      crucial role in the pathophysiology of AD.

PMID- 9583752
TI  - The modulatory effects of bradykinin B1 and B2 receptor antagonists upon viscero
      visceral hyper-reflexia in a rat model of visceral hyperalgesia.
AB  - This study assessed the relative involvement of the two bradykinin (Bk) receptors
      (B1 and B2) in the viscero-visceral hyper-reflexia (VVH) and plasma extravasation
      observed in an animal model of cystitis. The effects of the competitive receptor
      antagonists des-Arg9[Leu8]-Bk (B1) and HOE 140 (B2) were tested both in
      prophylactic (pre-inflammation administration) and therapeutic (post-inflammation
      administration) scenarios. Compared with control animals, des-Arg9[Leu8]-Bk had
      no effect on the hyper-reflexic response of the bladder to inflammation unless it
      was administered 5 h after inflammation. However, HOE 140 was able to attenuate
      the inflammation-induced viscero-visceral hyper-reflexia (VVH) at doses of 1
      mg/kg, 2 mg/kg and 7.5 mg/kg. This effect was apparent whether the drug was
      administered before, or after inflammation. In contrast, neither compound was
      effective in attenuating the intravesical plasma extravasation induced by
      turpentine. The data therefore suggest that the VVH and tissue inflammation
      responses are mediated via different mechanisms. In addition, the turpentine
      induced VVH appears to be mediated, at least partially, by the B2 receptor in the
      early phase, with the B1 receptor only becoming important later.

PMID- 9583753
TI  - Prediction and assessment of the severity of post-operative pain and of
      satisfaction with management.
AB  - A prospective observational study of cohorts of patients undergoing hip
      replacement (30), knee replacement (31), and spinal nerve root decompressive
      surgery (30) were interviewed pre-operatively to identify factors which might
      correlate with and potentially predict severe post-operative pain and
      dissatisfaction with analgesic management. The hip patients comprised 33% females
      and averaged 64 years, while the knee patients were 45% female and older (mean 71
      years) and the spinal patients were 43% female and averaged 50 years. The three
      groups were similar with respect to all other pre-operative variables. Pain
      intensity was assessed mainly by self-report using the Present Pain Intensity
      (PPI) and Visual Analogue Scales (VAS) of the McGill Pain Questionnaire. The PPI
      was preferred by patients and nurses and, as there were no analytical advantages
      for the VAS, the PPI data are presented. The average post-operative pain during
      routine management mainly with patient controlled intravenous opiate, was mild to
      moderate and declined over days 1-5, declined further at discharge but rose
      slightly 1 month after discharge. The hip replacement patients experienced
      significantly (P < 0.01) less pain overall than the patients in the other two
      groups. Nurses' assessments of pain severity from observed behaviour were low and
      agreed poorly with the patients' self reports. Assessed on Likert Scales (0-6),
      the patients generally indicated good or excellent pain control, better than
      expected pain experience, and high levels of satisfaction with analgesic
      management. Significant (P < or = 0.01) multivariate correlates of severe post
      operative pain assessed by logistic regression analysis of 11 variables were
      female gender, high pre-operative pain severity, and younger age. Significant (P
      < or = 0.01) multivariate correlates of both worse than expected pain experience
      and low satisfaction were female gender, high pre-operative pain severity, high
      anxiety about risks and problems, low expected pain severity, age (younger) and
      high willingness to report pain. These variables may reasonably be tested in
      further studies as potential predictors of adverse post-operative pain
      experience.

PMID- 9583754
TI  - When somatic information threatens, catastrophic thinking enhances attentional
      interference.
AB  - Styles of catastrophic thinking about pain have been related to an inability to
      divert attention away from pain. We investigated whether pain catastrophizers
      displayed high attentional interference during a threatening low-intensity
      electrocutaneous stimulus (ES). In Experiment 1, 44 undergraduates performed a
      tone discrimination task whilst experiencing several times an ES on the left or
      right arms. Tones were also presented 250 ms and 750 ms after ES onset.
      Participants were threatened that a high-intensity painful stimulus would occur
      at one site. As predicted, pain catastrophizers displayed pronounced task
      interference immediately after threat stimulus onset. In Experiment 2, threat was
      induced in 36 undergraduates by informing them that an ES excites pain fibres.
      Again, catastrophizers had marked interference immediately after onset. The
      results are discussed in terms of how catastrophizing amplifies somatosensory
      information and primes fear mechanisms.

PMID- 9583755
TI  - Pain following human brachial plexus injury with spinal cord root avulsion and
      the effect of surgery.
AB  - Brachial plexus injury leading to spinal cord root avulsion in humans produces a
      characteristic constant crushing and intermittent shooting pain, which is often
      intractable. Preliminary observations suggested that this pain might be
      alleviated after successful nerve transfers to restore limb function. We
      therefore studied a group of 14 patients prospectively, to establish the validity
      of this observation, and to elucidate the underlying mechanisms. We found a
      strong correlation and temporal relationship between reduction in pain and
      successful nerve repair. All five patients with motor recovery experienced
      significant relief of de-afferentation pain, while in the seven patients with
      persistent pain, none had motor recovery. There was no correlation between pain
      relief and the minimal recovery of sensation in some cases, and no case had any
      return of sensory or sympathetic cutaneous axon-reflexes. While skin sympathetic
      axon-reflexes were reduced with T1 root lesions, there was no relationship
      between T1 root damage and pain. It was concluded that nerve repair can reduce
      pain from spinal root avulsions and that the mechanism may involve successful
      regeneration, and/or restoration of peripheral connections prior to their
      function, possibly in muscle.

PMID- 9583756
TI  - Treatment of chronic allodynia in spinally injured rats: effects of intrathecal
      selective opioid receptor agonists.
AB  - We examined the effects of intrathecal (i.t.) selective opioid receptor agonists
      in alleviating mechanical and cold allodynia in spinally injured rats. Both DAMGO
      ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a mu-opioid receptor agonist) and DPDPE
      ([D-Phe2,D-Phe5]-enkephalin, a delta-opioid receptor agonist) dose-dependently
      relieved the chronic allodynia-like behavior at doses selective for their
      respective receptors. The anti-allodynic effect of DAMGO and DPDPE was reversed
      by the selective mu- and delta-opioid receptor antagonists CTOP (D-Phe-Cys-Tyr-D
      Trp-Orn-Thr-Pen-Thr-NH2) and naltrindole, respectively. In contrast, the
      selective kappa-opioid receptor agonist U50488H did not alleviate the allodynia
      like behavior, but rather enhanced it. The anti-nociceptive and anti-allodynic
      effect of i.t. DAMGO was blocked by U50488H. Thus, activation of spinal mu- and
      delta-, but not kappa-opioid receptors produced anti-allodynic effect in this
      model of central pain. Drugs which act selectively on opioid receptor subtypes
      may be useful in managing chronic central pain of spinal cord origin.

PMID- 9583757
TI  - Involvement of NK-1 and NK-2 tachykinin receptor mechanisms in jaw muscle
      activity reflexly evoked by inflammatory irritant application to the rat
      temporomandibular joint.
AB  - An electromyographic (EMG) study was carried out in 51 anesthetized rats to
      assess if neurokinin, NK-1 and NK-2, receptor mechanisms and tachykinins were
      involved in the increased jaw muscle activity which can be reflexly evoked by
      injection of the small-fiber excitant and inflammatory irritant mustard oil (MO)
      into the temporomandibular joint (TMJ) region. A baseline level of EMG activity
      was recorded bilaterally for 20 min from digastric (DIG) and masseter (MASS)
      muscles and then each animal was treated with NK-1 or NK-2 antagonist or vehicle.
      In one series of experiments either the NK-1 antagonist CP-99,994 (20 microg
      approximately 54 nmol), the NK-2 antagonist MEN-10,376 (10 microg approximately 9
      nmol or 20 microg approximately 18 nmol) or vehicle (control) was administrated
      into the lateral ventricle (i.c.v.); in another series the NK-1 antagonist (4
      mg/kg approximately 3-4 micromol/rat) or vehicle (control) was given
      intravenously (i.v.). After 10 min, MO (20 microl, 20%) was applied to one TMJ
      (first injection) and 45 min later, MO was applied to the opposite TMJ (second
      injection). Pretreatment with neurokinin antagonists had little effect on the
      incidence of the MO-evoked EMG responses but did significantly reduce the EMG
      magnitude and duration. In the animals pretreated with NK-1 antagonist only the
      responses to the second MO injection was significantly affected whereas NK-2
      pretreatment reduced the EMG responses to both MO injections to the TMJ. The
      systematic depression of the MO-evoked EMG responses by the NK-2 antagonist
      suggests that neurokinin A may be involved in the EMG responses. Since the NK-1
      antagonist produced no systematic changes in responses elicited by the first MO
      injection, substance P does not seem to be associated directly with the
      initiation or maintenance of the EMG responses but may be involved if a 'central
      sensitization' has been induced by the first MO injection to the TMJ.

PMID- 9583758
TI  - Empirical evidence of the association between the presence of musculoskeletal
      pain and physical disability in community-dwelling senior citizens.
AB  - The proportion of people 65 years of age and older who report musculoskeletal
      pain and physical disability is high. The main objective of this study was to
      determine whether physical disability was associated with the presence of
      musculoskeletal pain in a sample of senior citizens. Self-administered
      questionnaires were sent to a sample of 1306 community-dwelling senior citizens
      in London, Ontario, Canada between August and October 1995. The questionnaire
      included questions about pain, difficulty performing activities, depressive
      symptoms, chronic conditions, and demographic information. A total of 887 seniors
      completed the questionnaire (70.7% response rate, aged 65-94, 41.2% men, 58.8%
      women). Logistic regression analysis, without controlling for potential
      confounding variables, revealed that those who reported having musculoskeletal
      pain were seven times more likely to have some difficulty performing three or
      more activities listed in the questionnaire (OR = 6.91 95% CI 4.92-9.69). When
      significant confounding variables were controlled in the analysis, seniors who
      reported musculoskeletal pain were still three times more likely to have some
      difficulty with three or more activities (OR = 2.93, 95% CI 1.96-4.38). Although
      no causal relationship can be inferred, thorough pain assessment and pain
      management may be important in the maintenance of independent living for adults
      65 years of age or older.

PMID- 9583759
TI  - Patient empowerment and feedback did not decrease pain in seriously ill
      hospitalized adults.
AB  - We tested a nurse clinician-mediated intervention to relieve pain in a group of
      seriously ill hospitalized adults using a randomized controlled trial at five
      tertiary care academic centers in the US. The study included 4804 patients
      admitted between January 1992 and January 1994 with one or more of nine high
      mortality diagnoses; 2652 were allocated to the intervention and 2152 to usual
      care. Specially-trained nurse clinicians assessed patients' pain, educated them
      and their families about pain control, empowered patients to expect pain relief,
      informed patients' nurses and physicians about level of pain and suggested or
      used other pain management resources. Patients' pain was determined from hospital
      interviews with patients and surrogates. Pain 2 and 6 months later or after death
      and satisfaction with its control at all time periods were also assessed. All
      analyses were adjusted for baseline risk of being in pain and propensity to be in
      the intervention group. Overall, 50.9% of patients reported some pain. After
      adjustment for other variables associated with pain, comparing the intervention
      to the control group, there was not a statistically significant difference in
      level of pain (OR for higher levels of pain 1.15; CI 1.00-1.32) or satisfaction
      with control of pain during the hospitalization (OR for higher levels of pain
      1.12; CI 0.91-1.39), 2 or 6 months after discharge, or during the last 3 days of
      life. A multifaceted intervention using information, empowerment, advocacy,
      counseling and feedback was ineffective in ameliorating pain in seriously ill
      patients. Control of pain in these patients remains an important problem. More
      intensive pain treatment strategies addressing the needs of seriously ill
      hospitalized adults must be evaluated.

PMID- 9583760
TI  - Analysis of excitatory amino acid transmission within the rostral ventromedial
      medulla: implications for circuitry.
AB  - Two classes of neurons with distinct responses to opioids have been identified in
      the rostral ventromedial medulla (RVM), a region with a well-documented role in
      nociceptive modulation. 'On-cells' are directly inhibited by opioids, and opioids
      can thus gain access to the modulatory circuitry of the RVM by an action on these
      neurons. 'Off-cells' are likely to exert a net inhibitory effect on nociceptive
      processing, and are activated by opioids. Because the opioid activation of off
      cells is indirect, it has been proposed that on-cells function as inhibitory
      interneurons, and that opioid-induced suppression of on-cell firing in turn
      activates off-cells via disinhibition. The aim of the present study was to test
      this possibility. We had previously shown that excitatory amino acid (EAA)
      neurotransmission is crucial to the nocifensor reflex-related on-cell burst. We
      therefore infused the non-selective EAA receptor antagonist kynurenate (0.5-2
      nmol, 200-500 nl) into the RVM while recording activity of on-, off- and neutral
      cells in lightly anesthetized rats. Kynurenate infusions produced a significant
      decrease in on-cell firing, with suppression of the on-cell burst. Off-cells
      nonetheless continued to display a tail flick-related pause in firing. Tail flick
      latency was used as an index of nociceptive responsiveness, and was unaffected by
      kynurenate infusions. These results demonstrate that a burst of on-cell firing is
      not required in order for the off-cell to exhibit a reflex-related pause in
      discharge, and do not support the proposed crucial role for on-cells as
      inhibitory interneurons within the RVM. In addition, preferential suppression of
      on-cell tiring was not associated with an increase in tail flick latency. This
      suggests that, under the conditions of these experiments, on-cell discharge is
      not a potent regulator of moment-to-moment variations in nociceptive
      responsiveness.

PMID- 9583761
TI  - Use of levodopa to relieve pain from painful symmetrical diabetic polyneuropathy.
AB  - Levodopa has been used to treat some painful conditions and found to be effective
      in neuropathic pain due to herpes zoster in a double-blind study. From our
      anecdotal observations about the efficacy of levodopa on diabetic neuropathic
      pain, we designed a double-blind placebo-controlled study to test levodopa in
      painful diabetic neuropathy. Twenty-five out-patients with painful symmetrical
      diabetic polyneuropathy were admitted to the study. Fourteen patients were given
      100 mg levodopa plus 25 mg benserazide to be taken three times per day for 28
      days. Eleven patients were given identical placebo capsules. A blinded
      neurologist evaluated the patients clinically and performed Visual Analogue Scale
      (VAS) measurement every week from day 0 to day 28. The results seemed promising
      and levodopa may be a choice for the control of pain in neuropathy for which we
      do not have many alternative treatments.

PMID- 9583763
TI  - A fitness programme for patients with chronic low back pain: 2-year follow-up of
      a randomised controlled trial.
AB  - The aim of this study was to assess the long-term effect of a supervised fitness
      programme on patients with chronic low back pain. The design of the study was a
      single blind randomised controlled trial with follow-up, by postal questionnaire,
      2 years after intervention. The Oswestry Low Back Pain Disability Index was used
      as the outcome measure to assess daily activity affected by back pain. Eighty-one
      patients with chronic low back pain, who were referred to the physiotherapy
      department of a National Health Service orthopaedic hospital, were randomised to
      either a supervised fitness programme or a control group. Patients in the
      intervention group and control group were taught specific exercises to be
      continued at home and referred to a backschool for back care education. In
      addition, the intervention group attended eight sessions of a supervised fitness
      programme. Sixty-two patients (76%) with a mean age of 37 years, returned the
      Oswestry Low Back Pain Disability Index questionnaire. Of these, 29 were in the
      intervention group and 31 in the control group. Patients in the intervention
      group demonstrated a mean reduction of 7.7% in the Oswestry Low Back Pain
      Disability Index score (95% confidence interval of mean paired difference 3.9,
      11.6 P < 0.001), compared with only 2.4% in the control group (95% confidence
      interval of mean paired difference -2.0, 6.9 P > 0.05). Between group comparisons
      demonstrated a statistically significant difference in disability scores between
      the treatment and control group (mean difference 5.8, 95% confidence interval
      0.3, 11.4 P < 0.04). This study supports the current trend towards a more active
      treatment approach to low back pain. We have demonstrated clinical effectiveness
      of a fitness programme 2 years after treatment but this needs to be replicated in
      a larger study which should include a cost effectiveness analysis, further
      analysis of objective functional status and a placebo intervention group.

PMID- 9583762
TI  - Effects of systemic carbamazepine and gabapentin on spinal neuronal responses in
      spinal nerve ligated rats.
AB  - There are few pharmacological studies of central neuronal measures in animal
      models of neuropathic pain. In the present study we have compared the effects of
      two anticonvulsants, carbamazepine and gabapentin, on spinal neuronal responses
      of nerve injured rats (selective ligation of spinal nerves L5 and L6, SNL) and
      sham-operated rats. The development and maintenance of cooling and mechanical
      allodynia of the lesioned hindlimb of SNL rats was followed with behavioural
      indices. The contralateral hindlimb of SNL rats and the ipsilateral hindlimb of
      sham-operated rats did not develop allodynia. Electrophysiological studies of SNL
      rats were then performed at two post-operative (PO) time points (PO days 7-10 and
      PO days 14-17). Spinal neurones of SNL rats, but not sham-operated rats,
      exhibited spontaneous activity at both PO days 7-10 and 14-17 (1 +/- 0.4 and 3 +/
      1 Hz, respectively). Paradoxically, the magnitude of electrical (C-fibre) and
      natural (mechanical and thermal) evoked neuronal responses of SNL rats at PO days
      14-17 were smaller than the evoked neuronal responses of SNL rats at PO days 7-10
      and sham-operated rats. The electrical evoked A-fibre responses of neurones were
      comparable for the three groups of rats. Both subcutaneous carbamazepine (0.5
      22.5 mg/kg) and gabapentin (10-100 mg/kg) significantly reduced the spontaneous
      activity of spinal neurones of SNL rats at both PO time points. Carbamazepine had
      inhibitory effects on electrical C- and A-fibre and mechanical punctate (9 and 50
      g) evoked neuronal responses of SNL rats which were significantly different to
      the lack of effect of carbamazepine on these measures in sham-operated rats.
      Gabapentin had comparable effects as carbamazepine on the electrical C-and A
      fibre and mechanical punctate (9 and 50 g) evoked neuronal responses of SNL rats.
      In contrast to carbamazepine, gabapentin also reduced evoked neuronal responses
      of sham-operated rats and there was no difference between the effects of
      gabapentin in SNL and sham-operated rats. Robust behavioural changes in the SNL
      model of neuropathy are paralleled by a temporal increase in spontaneous activity
      and a paradoxical decrease in evoked spinal neuronal responses. The peripheral
      nerve dysfunction reveals an effect of carbamazepine which is maintained
      throughout the observation period, validating this experimental approach.
      Gabapentin, a novel treatment for neuropathic pain states, also reduced neuronal
      responses, but the actions of the drug were not dependent on nerve injury.
      Further studies at the spinal level may shed light on the physiology and
      pharmacology of the aberrant processes associated with neuropathic pain.

PMID- 9583764
TI  - UP 202-56, an adenosine analogue, selectively acts via A1 receptors to
      significantly decrease noxiously-evoked spinal c-Fos protein expression.
AB  - The effects of oral administration of UP 202-56, an adenosine analogue, were
      assessed on carrageenan-induced spinal c-Fos protein expression and peripheral
      oedema. Three hours after intraplantar injection of carrageenan (6 mg/150 microl
      of saline), in awake rats, numerous c-Fos-like immunoreactive (c-Fos-LI) neurons
      in the dorsal horn of L4-L5 lumbar segments of the spinal cord (191 +/- 8; 184 +/
      10; 205 +/- 7 c-Fos-LI neurons per 40 microm section, for carrageenan controls
      in three experimental series performed in this study, respectively) and an
      extensive peripheral oedema were observed. Oral UP 202-56 (10, 30 or 50 mg/kg)
      dose-dependently reduced the number of carrageenan-induced c-Fos-LI neurons (r =
      0.931. P < 0.0001), with the highest dose of UP 202-56 producing 72 +/- 4%
      reduction of the total number of carrageenan-induced spinal c-Fos-LI neurons, and
      12 +/- 3% and 33 +/- 6% of reduction of control carrageenan oedema at paw and
      ankle levels, respectively. DPCPX (1 mg/kg i.p.), a selective adenosine A1
      receptor antagonist, which injected alone had no effect on carrageenan-induced
      spinal c-Fos expression and peripheral oedema, blocked the effects of UP 202-56
      (30 mg/kg p.o.) on the number of carrageenan-induced c-Fos-LI neurons. In
      addition, DPCPX did not modify the effects of UP 202-56 on carrageenan-induced
      peripheral oedema. DMPX (1 mg/kg i.p.), a somewhat selective adenosine A2
      receptor antagonist, which injected alone had no significant effect on
      carrageenan-induced spinal c-Fos protein expression and peripheral oedema, did
      not influence the effects of UP 202-56 (30 mg/kg p.o.) on both carrageenan
      induced spinal c-Fos expression and peripheral oedema. Our results demonstrate
      that UP 202-56 dose-dependently reduced the spinal c-Fos protein expression in
      carrageenan model of inflammatory pain. The ability of DPCPX to block the effect
      of UP 202-56, in contrast to the lack of effect of DMPX, increased evidence for a
      predominant role of adenosine A1 receptors activation in the mechanism of action
      of UP 202-56. These results increase evidence for a role of adenosine in the
      modulation of nociceptive transmission and support the antinociceptive action of
      adenosine analogues, such as UP 202-56, in inflammatory pain processes.

PMID- 9583765
TI  - Differential sensory-motor effects of pentobarbital in intact rats genetically
      selected for high vs. low neuropathic pain-related behaviour.
AB  - Denervation of the hindpaw in rodents triggers autotomy, a behaviour of licking,
      scratching and self-mutilation of the denervated paw. This behaviour has been
      used as a model of paraesthesia, dysaesthesia and neuropathic pain. HA and LA
      rats are lines that have been genetically selected for high or low levels of
      autotomy, respectively. Compared to intact LA rats, HA rats are more sensitive to
      convulsions induced by pentylenetetrazol (PTZ), a blocker of the chloride channel
      associated with the GABA(A) receptor. Here we tested whether an acute
      administration of a sedative but not anaesthetic dose of pentobarbital (PB) would
      differentiate between these rat lines, in a number of sensory and motor tests
      performed in intact rats. This drug was tested since in contrast to PTZ, PB
      enhances central nervous system (CNS) inhibition by increasing chloride flux
      through the same channel. We found that PB was significantly more ataxic,
      antinociceptive, and reduced touch sensitivity in LA rats, compared to HA rats.
      These results suggest that HA and LA rats genetically differ in the levels of
      central inhibitions mediated by the GABA system presumably at the chloride
      channel. This difference may be associated with the dichotomous expression of
      neuropathic pain in these rat lines.

PMID- 9583766
TI  - Patient-controlled versus staff-controlled analgesia with pethidine after
      allogeneic bone marrow transplantation.
AB  - Patients treated by allogeneic bone marrow transplantation (aBMT) suffer
      prolonged oropharyngeal mucositis pain. The aim of this study was to
      prospectively compare patient-controlled analgesia (PCA) with an established
      regimen of staff-controlled analgesia using pethidine (meperidine). Twenty
      patients undergoing aBMT for haematologic neoplasias or malignant lymphomas
      randomly received pethidine intravenously either continuously plus supplemental
      bolus doses on request through the transplant unit staff or by PCA. Pain
      intensity was assessed by patient self report using a visual analogue scale (VAS)
      and daily pethidine intake was documented. In addition, the pethidine consumption
      of 20 aBMT-patients receiving staff-controlled analgesia prior to initiation of
      the study, but not reporting pain, was compared retrospectively with that of
      patients receiving the same analgesia regimen under study conditions. PCA
      significantly diminished both pethidine consumption and pain intensity compared
      with staff-controlled analgesia. The maximum pethidine intake was 440.1 +/- 111.8
      mg/24 h in the patient-controlled and 640.9 +/- 128.9 mg/24 h in the staff
      controlled analgesia group (mean +/- 95% CI). Mean pain scores remained under 50%
      but reached 70% in the staff-controlled analgesia group. Pethidine dosage by
      staff-controlled analgesia increased under study conditions, suggesting that mere
      pain-assessment and a 'competing' analgesic method motivated the BMT-unit staff
      to administer higher pethidine doses. This observation is discussed as a possible
      Hawthorne effect. Previous studies using morphine demonstrated that PCA
      diminishes opioid requirement compared to continuous or staff-controlled
      application in bone marrow recipients. In contrast to these studies, PCA
      additionally improved pain relief in the present investigation.

PMID- 9583767
TI  - The specific effects of prior opioid exposure on placebo analgesia and placebo
      respiratory depression.
AB  - Although in most of the cases the placebo response appears to be unpredictable,
      several factors have been considered in order to explain the placebo analgesic
      effect. For example, it is widely recognized, albeit with little empirical
      evidence, that placebo analgesia is more likely to occur after a successful
      analgesic therapy. On the basis of this assumption, we tested the placebo
      response in a population of patients who were treated with buprenorphine the day
      before for relieving postoperative pain. However, due to the high variability of
      opioid responsiveness, buprenorphine was effective in some patients and poorly
      effective in some others. Similarly, buprenorphine produced respiratory
      depression with a large variability, ranging from mild depression to no effect.
      We found that the placebo analgesic response depended on the buprenorphine
      analgesic effectiveness of the previous day. Analogously, we found that a placebo
      respiratory depressant response was more pronounced in those patients with a
      respiratory depressant response to buprenorphine on the day before, irrespective
      of the analgesic effectiveness. These specific effects suggest that (1) the
      placebo effect is experience-dependent; (2) the mechanisms underlying placebo
      analgesia and placebo respiratory depression are independent from each other and,
      by considering the role of endogenous opioids in placebo analgesia, might involve
      different subpopulations of opioid receptors.

PMID- 9583768
TI  - The relationship between sensory thresholds and mechanical hyperalgesia in nerve
      injury.
AB  - The paradoxical combination of sensory loss within the area where pain is felt
      together with pain evoked by non-noxious stimuli (allodynia) is a characteristic
      feature of neuropathic pain. This study examined the relationship between
      (mechanical and thermal) pain thresholds and dynamic and static hyperalgesia in
      15 patients with traumatic nerve injury and brush-evoked pain. Sensory tests were
      carried out both in the allodynic skin area and in the unaffected contralateral
      mirror image skin. The sensory characteristics included: visual analogue scale
      (VAS) score of ongoing pain, detection and pain threshold to thermal and
      mechanical stimuli, and temporal summation to repetitive heat and pinprick
      stimuli. Temporal summation was evoked by pinprick stimuli at 2.0 Hz but not at
      0.2 Hz in allodynic skin. No difference was observed in temporal summation to
      heat stimuli. There was a significant and inverse relation between heat and cold
      pain difference and mechanically evoked pain. Patients with heat hyperalgesia had
      a significantly higher VAS score of mechanical hyperalgesia than patients with
      heat hypoalgesia. There was no relationship between dynamic and static evoked
      hyperalgesia. These findings suggest a differential processing of repetitive
      thermal and mechanical stimuli in the central nervous system. Both dynamic and
      static mechanical hyperalgesia are maintained by activity in heat-sensitive
      nociceptors, but they are probably mediated by distinct mechanisms.

PMID- 9583770
TI  - Psychophysical evidence for a neuropathic component of chronic neck pain.
AB  - Recent studies into the common complaint of chronic neck pain have focused on its
      anatomical origin, identifying especially the cervical zygapophysial joints.
      However the pathophysiology of chronic neck pain remains poorly understood. In
      this psychophysical study, responses to electrocutaneous stimulation in subjects
      with chronic neck pain were examined. In an ascending method of limits design.
      electrical stimuli at 100 Hz with variation in current from 0 to 45 mA and in
      pulse width from 100 to 1000 micros were delivered transcutaneously to two points
      2 cm from the midline bilaterally at the levels of C5/6 and C7/T1 in 35 subjects
      with chronic neck pain and 22 pain-free volunteers. There was a small difference
      in detection threshold between the two groups: both pain threshold and pain
      tolerance were significantly lower in the pain group compared with pain free
      controls. These findings define hyperalgesia psychophysically and, taken together
      with the absence of tissue damage at the sites of testing. suggest that these
      painful cervical regions may be examples of secondary hyperalgesia which, in
      turn, implies central sensitisation of nociceptive pathways. These results are
      compatible with studies which identify potential anatomical origins of chronic
      neck pain but provide evidence that central sensitisation may be the relevant
      mechanism of pain production.

PMID- 9583769
TI  - Experimental muscle pain increases the human stretch reflex.
AB  - In this study we investigated the effect of human experimental muscle pain on H-
      and stretch reflexes as indicators of changes in muscle spindle sensitivity.
      Fourteen healthy, male volunteers participated in the study. Muscle pain was
      produced by infusion of 5% hypertonic saline over a period of 10-15 min in m.
      soleus and in m. tibialis anterior. Reflexes were elicited in the relaxed and
      active soleus muscle (10-15 Nm ankle torque) before, during and after muscle
      pain. Control measurements were made with infusions of 0.9% isotonic saline.
      Surface electromyograms (EMG) were measured from the soleus muscle, and torque
      was measured from the ankle joint. With pain in the soleus muscle the mechanical
      stretch reflex response (ankle torque) increased significantly (P = 0.0007) as
      compared to before pain. With pain in the tibialis anterior muscle both the
      mechanical and EMG responses increased significantly (P = 0.001; P = 0.0003) as
      compared to before pain. The H-reflex showed no significant changes during the
      infusions in either muscles. This study has demonstrated a muscle pain-related
      increase in the amplitude of the stretch reflex without a corresponding increase
      in the H-reflex amplitude. One explanation could be an increased dynamic
      sensitivity of the muscle spindles during muscle pain caused by an increased
      firing rate in the dynamic gamma-motoneurones. However, the data could not
      support the vicious cycle model because the excitability of the alpha-motoneurone
      pool was unchanged.

PMID- 9583771
TI  - The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in
      cancer patients: a double blind, randomized, placebo controlled trial.
AB  - Neuropathic pain is often severe, persistent, and responds poorly to analgesic
      medications. Recent evidence suggests that N-methyl-D-aspartate (NMDA) receptor
      antagonists may be effective in the treatment of neuropathic pain. The present
      trial was designed to test the efficacy of acute administration of the NMDA
      receptor antagonist amantadine in relieving surgical neuropathic pain in patients
      with cancer. The study sample consisted of 15 cancer patients with the diagnosis
      of surgical neuropathic pain. Two 500 ml infusions of either 200 mg amantadine or
      placebo were administered over a 3 h period, in a randomized order, 1 week apart
      from each other. Spontaneous and evoked pain were measured for 48 h before
      treatment, during treatment, and for 48 h following treatment. An average pain
      reduction of 85% was recorded at the end of amantadine infusion vs. 45% following
      placebo administration. The difference in pain relief between the two treatments
      was statistically significant (P = 0.009). Mean pain intensity remained
      significantly lower during the 48 h following amantadine treatment as compared
      with the 48 h prior to treatment (31% reduction; P = 0.006), whereas no such
      effect was found with the placebo (6% reduction; P = 0.40). Amantadine, but not
      the placebo, also reduced 'wind up' like pain (caused by repeated pinpricking) in
      four patients. We conclude that amantadine infusion is a safe and effective acute
      treatment for surgical neuropathic pain in cancer patients. Further trials with
      long-term oral or parenteral amantadine treatment should be conducted.

PMID- 9583773
TI  - The cold plate as a test of nociceptive behaviors: description and application to
      the study of chronic neuropathic and inflammatory pain models.
AB  - A cold plate apparatus was designed to test the responses of unrestrained rats to
      low temperature stimulation of the plantar aspect of the paw. At plate
      temperatures of 10 degrees C and 5 degrees C, rats with either chronic
      constriction injury (CCI) of the sciatic nerve or complete Freund's adjuvant
      (CFA) induced inflammation of the hindpaw displayed a stereotyped behavior. Brisk
      lifts of the treated hindpaw were recorded, while no evidence of other
      nociceptive behaviors could be discerned. The most consistent responses were
      obtained with a plate temperature of 5 degrees C in three 5-min testing periods,
      separated by 10-min intervals during which the animals were returned to a normal
      environment. Concomitantly to cold testing, the rats were evaluated for their
      response to heat (plantar test) and mechanical (von Frey hairs) stimuli. In both
      injury models, while responses to heat stimuli had normalized at 60 days post
      injury, a clear lateralization of responses to cold was observed throughout the
      entire study period. Systemic lidocaine, clonidine, and morphine suppressed
      responses to cold in a dose-related fashion. At doses that did not affect motor
      or sensory behavior, both lidocaine and its quaternary derivative QX-314
      similarly reduced paw lifts, suggesting that cold hyperalgesia is in part due to
      peripheral altered nociceptive processing. Clonidine was more potent in CCI then
      in CFA rats in reducing the response to cold. Paradoxically, clonidine increased
      the withdrawal latencies to heat in the CCI hindpaw at 40 days and thereafter, at
      a time when both hindpaws had the same withdrawal latencies in control animals.
      Morphine was also more potent on CCI than CFA cold responses, indicating that,
      chronically, CFA-induced hyperalgesia might be opiate resistant. Evidence for
      tonic endogenous inhibition of cold hyperalgesia was obtained for CFA rats, when
      systemic naltrexone significantly increased the number of paw lifts; this was not
      found in rats with CCI. At 60 days, neither morphine nor naltrexone affected cold
      induced paw lifting in CFA rats, suggesting that the neuronal circuit mediating
      cold hyperalgesia in these animals had become opiate insensitive. In conclusion,
      the cold plate was found to be a reliable method for detecting abnormal
      nociceptive behavior even at long intervals after nerve or inflammatory injuries,
      when responses to other nociceptive stimuli have returned to near normal. The
      results of pharmacological studies suggest that cold hyperalgesia is in part a
      consequence of altered sensory processing in the periphery, and that it can be
      independently modulated by opiate and adrenergic systems.

PMID- 9583774
TI  - Epileptic seizure associated with intracerebroventricular and intrathecal
      morphine bolus.
AB  - We report on two patients with morphine-related seizures associated with either
      intrathecal or intracerebroventricular administration. Both patients had a
      history of malignant tumor and both experienced the seizures following bolus
      application of morphine, while even higher dosages were well tolerated when
      continuously infused. Seizures occurred without signs of intoxication. Initiation
      of intrathecal morphine therapy and bolus application should be performed
      carefully and only when constant monitoring is provided for at least 12 h. Animal
      data and possible mechanisms for morphine-related seizures are discussed.

PMID- 9583772
TI  - Regional changes in forebrain activation during the early and late phase of
      formalin nociception: analysis using cerebral blood flow in the rat.
AB  - This is the first neural imaging study to use regional cerebral blood flow (rCBF)
      in an animal model to identify the patterns of forebrain nociceptive processing
      that occur during the early and late phase of the formalin test. We measured
      normalized rCBF increases by an autoradiographic method using the radiotracer
      [99mTc]exametazime. Noxious formalin consistently produced detectable, well
      localized and typically bilateral increases in rCBF within multiple forebrain
      structures, as well as the interpeduncular nucleus (Activation Index, AI = 66)
      and the midbrain periaqueductal gray (AI = 20). Structures showing pain-induced
      changes in rCBF included several forebrain regions considered part of the limbic
      system. The hindlimb region of somatosensory cortex was significantly activated
      (AI = 31), and blood flow increases in VPL (AI = 8.7) and the medial thalamus (AI
      = 9.0) exhibited a tendency to be greater in the late phase as compared to the
      early phase of the formalin test. The spatial pattern and intensity of activation
      varied as a function of the time following the noxious formalin stimulus. The
      results highlight the important role of the limbic forebrain in the neural
      mechanisms of prolonged persistent pain and provide evidence for a forebrain
      network for pain.

PMID- 9583775
TI  - Compatibility of ketamine and morphine injections.
AB  - The compatibility of ketamine and morphine mixture was studied. In addition, pH
      adjustment to minimise local tissue irritation led to no change in stability of
      the mixture up to pH 5.9. It appears that ketamine and morphine mixtures are
      stable over a 24 h period.

PMID- 9583776
TI  - The NMDA-receptor antagonist ketamine abolishes neuropathic pain after epidural
      administration in a clinical case.
AB  - A 14-year-old male patient developed severe right limb pain after traumatic
      sciatic nerve injury. His pain was diagnosed as neuropathic pain (complex
      regional pain syndrome, type II). He did not respond to any conventional therapy
      for limb pain including non-steroidal antiinflammatory drugs, antidepressants,
      anticonvulsants, continuous epidural administration of local anesthetics and
      psychotherapy. Following continuous epidural administration of a very low dose of
      ketamine, an N-methyl-D-aspartic acid (NMDA) receptor antagonist, 25 microg/kg
      per h for 10 days, complete pain relief was obtained without any side-effects.
      There has been no recurrence of pain for 8 months after discontinuation of
      epidural ketamine. The symptoms related to dysfunction of the sympathetic nervous
      system still remained after complete pain relief. We discuss pain mechanisms,
      pain relief and the use of ketamine in this case.

PMID- 9583777
TI  - Dysaesthetic neck pain with syncope.
AB  - Neurogenic dysaesthetic pain in the neck following surgery for tumours in the
      neck is rare. Rarer still is the combination of pain following surgery with
      syncope. We looked at four patients who had tumours within the neck excised and
      then went on to develop neurogenic dysaesthetic neck pain associated with
      syncope. Distinction is made between neurogenic dysaesthetic pain following neck
      surgery and glossopharyngeal neuralgia which has been previously reported in
      association with neck surgery and also glossopharyngeal neuralgia with syncope.
      Spinal cord stimulation was used successfully to treat the dysaesthetic pain and
      syncope in three of the patients while the fourth patient died from the effects
      of his tumour. Medical practitioners may wish to consider spinal cord stimulation
      in relation to treating neurogenic dysaesthetic neck pain with syncope.

PMID- 9583778
TI  - A case of 'pure' dynamic mechano-allodynia due to a lesion of the spinal cord:
      pathophysiological considerations.
AB  - We report the unusual observation of a patient who presented with the single
      symptom of a very intense, brush-induced allodynia (dynamic mechanical allodynia)
      which was strictly confined to the left C2 and C3 dermatomes. All investigations,
      including a cervical spinal MRI, were initially normal. The clinical picture
      remained stable for several months until the appearance of spontaneous pain and
      sensory deficits suggestive of a spinal lesion. A second MRI revealed an
      intraspinal lesion involving the C2-C5 segments. In accordance with other
      clinical and animal studies, such an observation of a 'pure' dynamic mechano
      allodynia suggests that specific mechanisms underlie each component of
      neuropathic pain. Possible pathophysiological mechanisms are discussed in the
      light of recent experimental results obtained in animals.

PMID- 9583779
TI  - Varicella-zoster virus distribution in Ramsay Hunt syndrome revealed by
      polymerase chain reaction.
AB  - The pathogenesis of facial nerve paralysis and vestibulo-cochlear dysfunction of
      Ramsay Hunt syndrome remains unclear as varicella-zoster virus (VZV) has not been
      demonstrated in the lesions. Using the polymerase chain reaction, we detected VZV
      genomes not only in the vesicles on the auricles or oral cavity but also in the
      facial nerve sheath, middle ear mucosa and cerebrospinal fluid from patients with
      Ramsay Hunt syndrome. The VZV genome was undetectable in the same kinds of
      clinical samples obtained from control patients with facial nerve paralysis of
      other etiologies. The results indicated that VZV spreads widely in the neural
      components, mucocutaneous tissue and cerebrospinal fluid. The present study will
      facilitate better understanding of the pathogenesis of facial nerve paralysis,
      vertigo, hearing impairment and other cranial nerve dysfunction of Ramsay Hunt
      syndrome.

PMID- 9583780
TI  - Sensitivity and specificity of transtympanic electrocochleography in Meniere's
      disease.
AB  - Transtympanic electrocochleography (TT ECoG) was conducted in 61 patients (61
      ears) with the clinical diagnosis of Meniere's disease and 15 patients (21 ears)
      with cochlear hearing loss of other aetiologies to assess the ability of the
      method to separate different cochlear disorders. The click-evoked summation
      potential/action potential (SP/AP) ratio and the 1 and 2 kHz burst-evoked SP
      amplitudes were evaluated. Based on the TT ECoG results from 13 normal hearing
      subjects (15 ears) the upper limit of each variable was determined, above which a
      value was considered pathological, i.e. indicative of endolymphatic hydrops. The
      results showed that the sensitivity of the SP/AP ratio was 62% and specificity
      95%. When evaluating the combinations of TT ECoG parameters with logistic
      regression, SP/AP ratio and 1 kHz burst-evoked SP amplitude were shown to
      increase the discriminating ability of TT ECoG significantly. Inclusion of the 1
      kHz burst-evoked SP amplitudes increased sensitivity to 82%, without changing
      specificity. Inclusion of the 2 kHz burst had no effect on sensitivity or
      specificity.

PMID- 9583781
TI  - The furosemide test and vestibular status in Meniere's disease.
AB  - A total of 62 ears of patients with typical Meniere's disease was examined by the
      furosemide test to detect endolymphatic hydrops. In 95% of the normal control
      group, the per cent change in the maximum velocity of the slow phase of caloric
      nystagmus (MVS) after injection of furosemide was under 10%. Therefore, a
      positive furosemide test was defined as a change in MVS of more than 10%. Thirty
      five (56%) of the 62 ears with typical Meniere's disease showed a positive
      furosemide test. When the affected ears were divided into two groups according to
      vestibular symptoms, only 11 (38%) of 29 inactive ears were positive while 24
      (73%) of 33 active ears were positive. There was a significant difference in the
      positive rate of the furosemide test between the ears with clinically inactive
      and active vestibular disease. The per cent canal paresis (CP%) was determined to
      assess canal excitability and a CP%> 25% was defined as canal paresis. There was
      no significant difference in the furosemide test positive rate between ears with
      canal paresis and ears with a normal CP%, although the former tended to show a
      greater MVS change. The response to the furosemide test showed no relationship to
      the results of pure tone audiometry. In conclusion, the furosemide test appears
      to indicate the vestibular status in various stages of Meniere's disease.

PMID- 9583782
TI  - Influence of optokinetic and vestibular stimuli on the performance of smooth
      pursuit eye movements: implications for a clinical test.
AB  - In real-life situations, such as during locomotion, or while driving a vehicle,
      it is necessary to maintain visual fixation and tracking in the presence of the
      visual flow of the surroundings, which represents a potentially adequate stimulus
      for the elicitation of optokinetic nystagmus. The present study is concerned with
      the influence of vestibular disorders, whether pathological or experimentally
      induced, on those cortically controlled fixation mechanisms, predominantly in the
      smooth pursuit system, which are involved in suppressing optokinetic information.
      The study examines the possibility of obtaining an objective measure to assist in
      counselling patients with unilateral vestibular loss on their vehicle driving
      ability. To this end, the influence of optokinetic and vestibular stimulation on
      the execution of smooth pursuit target tracking was measured by recording eye
      movements during a combination of standard pursuit tasks (0.25, 0.5 and 1 Hz
      sinusoidal) against standard optokinetic striped backgrounds (0, 30 and 60
      degrees/sec). The influence of vestibular imbalance, induced in healthy subjects
      (n = 35) by unilateral caloric irrigation, and caused by unilateral vestibular
      loss (in five patients), was also examined under these conditions. During induced
      vestibular imbalance in normal subjects, and to a greater extent in the tested
      patients, significant deficits in smooth pursuit gain and increases in saccade
      frequency were observed during target pursuit against an optokinetic background.
      Moreover, the findings indicate that the most sensitive parameter for the
      influence of vestibular optokinetic stimuli on smooth pursuit is frequency of
      saccades, rather than the gain factor. The tests described here are appropriate
      for clinical and medico-legal assessment of the influence of vestibular disorder
      on vehicle driving.

PMID- 9583783
TI  - Otolith and semicircular canal contributions to the human binocular response to
      roll oscillation.
AB  - Three normal human subjects were oscillated about their naso-occipital axis in a
      supine position at 0.4 Hz and 0.1 Hz, both in darkness and in the light with a
      structured fixation target. The same subjects were oscillated in roll about an
      upright position, at the same frequencies, in darkness; and also about axes
      directed 20 degrees and 40 degrees to the left and to the right of the
      midsagittal plane, at 0.4 Hz, in darkness. Three-dimensional binocular eye
      movements were recorded using video-oculography. All stimuli induced a
      predominantly torsional nystagmus with small disconjugate head-vertical (skew)
      and conjugate head-horizontal components. For roll oscillation, the torsional
      slow phase velocity gain was higher in the light and generally increased with the
      stimulation frequency. In darkness, only one subject had significantly higher
      torsional gains in the upright compared to the supine position (12% difference),
      suggesting that the otolith contribution to the roll response is minimal at the
      frequencies tested. The slow phase velocity gain of the skew increased with
      fixation in two subjects. but decreased in the third subject; these changes were
      related to changes in eye vergence. In the upright position, with oblique axes of
      rotation, the head-vertical eye movements were asymmetrical, with the outermost
      eye executing a larger amplitude movement. The disconjugate head-vertical eye
      movements observed can be explained by the pattern of vertical semicircular canal
      stimulation and their connections to the extraocular muscles. In humans, skewing
      of the eyes may compensate for the eccentricity of the foveae which lie in the
      temporal retina and undergo vertical translations in opposite directions when the
      eyes tort.

PMID- 9583784
TI  - Inner ridge cells may be the main source of tectorial membrane type II collagen:
      evidence from quantitative mRNA in situ hybridization.
AB  - In a previous study we showed that COL2A1 mRNA is expressed in both ectodermally
      and mesodermally derived structures of second trimester human fetal cochlea,
      whereas type II collagen is present in mesodermally derived structures and in
      tectorial and basilar membranes. Because the tectorial membrane is acellular and
      therefore does not make its own proteins, the source of type II collagen and
      proteoglycans in this membrane has been of interest. We have attempted to address
      this issue, at least in part, by performing quantitative cRNA mRNA in situ
      hybridization on second trimester human fetal cochlear sections using a COL2A1
      probe. By counting the number of silver grains cell in the interdental cells,
      inner sulcus cells and inner ridge Kolliker organ cells and by an analysis of
      variance of these quantitative data. inner ridge cells were found to have
      significantly higher levels of COL2A1 mRNA than interdental and inner sulcus
      cells (p < 0.0001). On the basis of significantly higher COL2A1 mRNA levels in
      inner ridge cells and their higher numbers than interdental and inner sulcus
      cells we postulate that type II collagen for human fetal tectorial membrane is
      derived mostly from inner ridge Kolliker organ cells. The lower COL2A1 mRNA in
      interdental cells appears to provide type II collagen for the spiral limbus and
      the tectorial membrane. The inner sulcus cells, hair cells. Deiter's and Hensen's
      cells also appear to contribute lesser amounts of type II collagen to the
      tectorial membrane. In analogy to these findings it is possible that other
      tectorial membrane proteins, including proteoglycans and other collagens, are
      also largely derived from these cells during human fetal development.

PMID- 9583785
TI  - Effects of the neurosteroid dehydroepiandrosterone sulfate on medial vestibular
      nucleus neurons.
AB  - Neurosteroids increase in concentration under conditions of stress and produce
      behavioral effects. An electrophysiological investigation was undertaken to
      determine whether dehydroepiandrosterone sulfate (DHEAS), a neurosteroid,
      influences the neuronal activity of medial vestibular nucleus (MVN) neurons in
      alpha-chloralose-anesthetized cats. Single neuronal activities in MVN were
      recorded extracellularly using a glass-insulated silver wire microelectrode
      attached along a seven-barreled micropipette. Each pipette was filled with DHEAS,
      GABA, muscimol (a GABA[A] receptor agonist) and baclofen (a GABA[B] receptor
      agonist), which were applied microiontophoretically to the immediate vicinity of
      the target neurons. The effects of these chemicals were examined on type I
      neurons. identified by responses to horizontal and sinusoidal rotations.
      Microiontophoretic application of DHEAS did not affect the spontaneous and
      rotation-induced firings of type I neurons, but dose-dependently blocked GABA
      induced inhibitory effects on type I neurons. In addition, both muscimol- and
      baclofen-induced inhibitions of firing were blocked by DHEAS. These results
      suggest that DHEAS suppresses GABAergic inhibitory effects on MVN neurons through
      both GABA(A) and GABA(B) receptors, presumably resulting in disturbance of
      control of neuronal activity in the vestibular nucleus and consequent development
      of vertigo.

PMID- 9583786
TI  - Membrane potential in isolated epithelial cells of the endolymphatic sac in the
      guinea-pig.
AB  - The membrane potential (Em) in epithelial cells isolated from the intermediate
      portion of the endolymphatic sac (ES) of the guinea-pig was recorded using the
      whole-cell patch-clamp technique. In the steady state the Em was -53.5+/-1.5 mV
      (n = 74), which is similar to that in epithelial cells of other tissues.
      Application of 1 MM ouabain induced a depolarization of Em by approximately 10 mV
      (n = 6), suggesting that an active ion transport process by Na+-K+-ATPase may be
      present in the ES epithelial membrane. Increasing extracellular K+ concentrations
      from 5 to 100 mM induced a significant membrane depolarization that was close to
      the K+ equilibrium potential calculated by the Nernst equation, indicating that
      K+ may be a predominant permeable ion in the ES epithelial membrane. Total
      replacement of extracellular Na+ with NMDG+ led to a significant membrane
      hyperpolarization of 38.7+/-2.5 mV (n = 18), suggesting that Na+ may be another
      major permeable ion for the ES epithelial membrane. Reducing extracellular Cl-
      concentrations from 149.3 to 7 mM had no significant effect on Em, indicating
      that Cl- may be a negligible permeable ion in the ES epithelial membrane.

PMID- 9583787
TI  - Effect of endoplasmic Ca2+-ATPase inhibitors on cochlear potentials in the guinea
      pig.
AB  - The effect of endoplasmic Ca2+-ATPase inhibitors on cochlear potentials was
      examined in the guinea-pig. Perilymphatic perfusion with thapsigargin (10[-6] M)
      produced a significant decrease in the amplitudes of cochlear microphonics,
      negative summating potential and compound action potential, and a significant
      prolongation of N1 latency with no change in the endocochlear potential. These
      changes were all dose dependent. Another endoplasmic Ca2+-ATPase inhibitor,
      cyclopiazonic acid (10[-5] M), produced the same effects as thapsigargin on
      cochlear potentials. These results suggest that endoplasmic Ca2+-ATPase
      inhibitors may have inhibitory functions on cochlear potentials.

PMID- 9583788
TI  - Aerobic and anaerobic bacteriology of otorrhea associated with tympanostomy tubes
      in children.
AB  - The microbiology of in 55 ear aspirates obtained from 34 children with chronic
      otorrhea was studied. Aspiration of the middle ear exudate was done immediately
      following removal of tympanostomy tube (TT). The middle ear aspirates and swab
      specimens of the external auditory canals were cultured for aerobic and anaerobic
      bacteria. Sixty-five isolates were recovered only from the middle ears, 73 only
      from the external ear canals, and 73 were present at both sites. Analysis of the
      138 middle ear isolates demonstrated the recovery of aerobic bacteria only in 28
      patients (50%), anaerobes only in seven (13%), and both aerobes and anaerobes in
      20 (36%). There were 77 aerobic and 61 anaerobic isolates. Commonly recovered
      aerobes were Pseudomonas aeruginosa (17 isolates), Staphylococcus aureus (11),
      Proteus sp. (7), Moraxella catarrhalis (6), Klebsiella pneumoniae (5) and non
      typable Haemophilus influenzae (5). Commonly isolated anaerobes were
      Peptostreptococcus sp. (25 isolates), Prevotella sp. (10), Bacteroides sp. (8)
      and Fusobacterium sp. (6). Pseudomonas aeruginosa and S. aureus were more often
      isolated in children older then 6 years. These findings demonstrate the
      polymicrobial bacteriology of TT-related otorrhea in children. Specimens
      collected from the external auditory canals can be misleading. Reliable
      information can be obtained from the ear exudes when collected through the TT or
      through the open perforation after their removal.

PMID- 9583789
TI  - Changes in mucosal goblet cell density in acute otitis media caused by non
      typeable Haemophilus influenzae.
AB  - The correlation between secretory otitis media and increased goblet cell density
      in the middle ear mucosa is well established. Previous studies have shown that a
      single episode of acute otitis media caused by Streptococcus pneumoniae is
      followed by increased goblet cell density for a period of at least 6 months,
      conceivably predisposing a subsequent development of secretory otitis media. In
      this study, 25 rat middle ears were inoculated with non-typeable Haemophilus
      influenzae in order to determine the effect on mucosal goblet cell density. Five
      rats were killed on days 4, 8, 16, 60 and 180 postinoculation, followed by
      dissection, staining and whole-mount embedding of the middle ear mucosae. The
      goblet cell density was determined in 24 well-defined localities. Compared with
      25 normal middle ears, the goblet cell density was significantly increased in
      almost all localities, at all days on which the animals were killed. Thus,
      increased goblet cell density and enlargement of mucosal areas containing goblet
      cells persisted 6 months after the acute incident. The induced increase of goblet
      cell density was higher than the increase following inoculation of S. pneumoniae.
      We conclude that acute otitis media caused by non-typeable H. influenzae is
      followed by a longstanding increase in mucosal secretory capacity, likely to
      predispose a subsequent development of secretory otitis media.

PMID- 9583790
TI  - Multifrequency tympanometry and histopathology in chinchillas with experimentally
      produced middle ear pathologies.
AB  - Middle ear lesions were produced in chinchillas by introducing fascia, Gelfoam,
      silastic or a combination of these materials into the labyrinthine and mastoid
      bullae. After 1-2 months, conventional 226 Hz and multifrequency tympanometry
      (MFT) were performed and the animals were sacrificed for histopathological
      analysis of the middle ear. Specific middle ear lesions were created including
      abnormal tympanic membrane thickness, tympanic membrane mass, tympanic membrane
      adhesion, mastoid bulla obstruction, ossicular adhesions and reduced middle ear
      volume. Several potentially strong associations emerged between tympanometric
      measures and pathological conditions. The strongest were the combinations of
      thick tympanic membrane and irregular multifrequency tympanograms, tympanic
      membrane mass and notched 226 Hz admittance tympanograms, tympanic membrane
      adhesions and low 226 Hz admittance, and tympanic membrane adhesions and low
      resonant frequency. 226 Hz static admittance had a sensitivity of 0.73 and a
      specificity of 0.75 for detecting significant middle ear pathology. Tympanometric
      width was not an effective diagnostic test, separately or in combination with
      static admittance. The most effective test based on 226 Hz measures was the
      combination of low admittance or admittance notch. MFT was superior to 226 Hz
      tympanometry. The combination of low resonance or double resonance or irregular
      patterns had a sensitivity and specificity of 0.91 and 1.0, respectively.
      Combining 226 Hz tympanometry with MFT improved the performance relative to 226
      Hz tympanometry alone but not relative to MFT alone. The results support clinical
      reports that multifrequency tympanometry detects some middle ear pathologies that
      are not detected by conventional 226 Hz tympanometry.

PMID- 9583791
TI  - The Scandinavian Odor-Identification Test: development, reliability, validity and
      normative data.
AB  - The Scandinavian Odor-Identification Test (SOIT) was developed to address the
      need for a culturally valid odor-identification test for clinical use on the
      Scandinavian population that (i) has good ability to generalize performance to
      olfactory status, (ii) assesses olfactory and trigeminal function separately,
      (iii) requires only limited cognitive demands, (iv) has normative data and good
      sensitivity and specificity, and (v) is fast, easy to administer and inexpensive.
      Sixteen odorous test stimuli were selected that were relatively identifiable,
      familiar, strong in intensity and pleasant according to healthy participants.
      Four response alternatives were then selected for each test stimulus based on a
      confusion matrix of identification rates obtained from healthy participants, in a
      manner that controlled for task difficulty. Results on the SOIT from healthy
      persons and hyposmic patients showed satisfactory test-retest reliability, split
      half reliability and validity. Cut-off scores for olfactory diagnosis (normosmia,
      hyposmia, anosmia) based on normative data obtained from 171 healthy persons
      showed a satisfactory sensitivity and specificity of the SOIT. Assessment of 22
      anosmic patients with the SOIT revealed that three of the test stimuli were
      significant trigeminal stimulants.

PMID- 9583792
TI  - Capsaicin desensitization of the nasal mucosa reduces symptoms upon allergen
      challenge in patients with allergic rhinitis.
AB  - Patients with birch pollen allergic rhinitis were treated locally, out of season,
      in the nasal cavity with capsaicin (30 microM) or saline. The capsaicin treatment
      resulted in a statistically significant reduction of symptoms upon allergen
      challenge, which lasted for 2 months. Saline had no effect on the symptom score
      upon allergen challenge. Neither capsaicin nor saline treatment had any effect on
      allergen challenge-induced nasal mucosal swelling monitored by acoustic
      rhinometry. Allergen challenge-induced eosinophil migration to the nasal mucosa
      was affected by neither capsaicin nor the saline treatment. The finding that
      capsaicin treatment reduces allergic symptoms indicates that selective, non
      peptide neurokinin receptor antagonists may be an alternative in the future in
      the treatment of nasal allergy. However, owing to the pain involved in local
      capsaicin treatment this treatment is unlikely to be of clinical use.

PMID- 9583793
TI  - Activated and non-activated eosinophils in patients with chronic rhinosinusitis.
AB  - Nasal polyps develop out of an oedematous swelling of the mucous membrane, which
      is probably a localized mediator-dependent reaction of the mucous membrane in the
      lamina propria. Among other things, eosinophil cationic protein (ECP) is released
      from activated eosinophils. In previous studies, ECP was considered as measuring
      the degree of allergic dermatological illnesses and therapy was given
      accordingly. A group of 54 patients with massive polyposis requiring functional
      endoscopic sinus surgery was examined. After surgery they were treated with local
      and systemic cortisone. Polypous tissue samples were collected and counted for
      the number and ratio of activated and non-activated eosinophils, and the serum
      titre of ECP was measured simultaneously using a fluoroimmunoassay (test kit,
      Kabi Pharmacia, Sweden). The aim of the study was to evaluate the activity of the
      disease and to gain hints for a specific therapy. The presence of these
      eosinophils was demonstrated by immunohistochemical methods, using EG1 antibodies
      against non-activated and EG2 antibodies against activated (i.e. secreted form of
      ECP) eosinophils. Depending on the duration of treatment with systemic and local
      corticosteroids, there was a considerable decrease in activated eosinophils and
      the level of serum ECP. Consequently, cortisone can be applied in the treatment
      of eosinophilic nasal polyps. As the number of activated eosinophils in the
      tissue is an indicator for the activity of the chronic inflammation it can be
      deduced from our study that local and/or systemic cortisone application
      successfully stops the growth of eosinophilic nasal polyps. The number and ratio
      of activated and non-activated eosinophils seem to be reliable indicators for the
      activity of chronic polyposis.

PMID- 9583794
TI  - Seasonal rise in interleukin-4 during pollen season is related to seasonal rise
      in specific IgE for pollens but not for mites.
AB  - Since IL-4 plays a key role in inducing and increasing the generation of not only
      primary polyclonal but also secondary specific IgE responses by B lymphocytes, a
      seasonal increase in IL-4 is likely to be involved in such seasonal rises in
      specific IgE in seasonal allergic rhinitis. The first aim of this study was to
      investigate the possible seasonal increase in serum IL-4 in patients with
      seasonal allergic rhinitis due to Japanese cedar pollens. If serum IL-4 increases
      in response to seasonal pollen exposure and is responsible for the seasonal
      increase in pollen-specific IgE in sera, this increase in IL-4 might
      theoretically affect specific IgE synthesis for other allergens. The second aim
      was to investigate the effect of natural pollen exposure on serum concentrations
      of house dust mite-specific IgE in patients who have seasonal allergic rhinitis
      and concurrent perennial allergic rhinitis due to house dust mites. This study
      included 55 adult patients with seasonal and perennial allergic rhinitis due to
      Japanese cedar pollens and Dermatophagoides farinae (D. farinae). Venous blood
      was collected twice from each patient, before and during the cedar pollen season
      1996, to determine IL-4, cedar pollen-specific IgE and D. farinae-specific IgE in
      sera. Both IL-4 and pollen-specific IgE in sera were significantly increased
      during the pollen season, and the seasonal increase rate in pollen-specific IgE
      was significantly correlated with the seasonal increase rate in IL-4. By
      contrast, D. farinae-specific IgE was not changed during the pollen season in
      these patients. In conclusion, an elevation of IL-4 in sera during the pollen
      season may play an important part in the seasonal rise in pollen-specific IgE,
      and enhancement of specific IgE synthesis is likely to need not only an increase
      in IL-4 but also an increase in the number and/or capacity of specific IgE
      secreting B cells.

PMID- 9583795
TI  - Changes in glycoconjugate expression of the sinus mucosa during experimental
      sinusitis: a lectin histochemical study of the epithelium and goblet cell
      development.
AB  - Lectin expression in both normal and inflamed sinus mucosa in rabbit was
      investigated histochemically. A different staining pattern was observed in the
      inflamed mucosa, i.e. the degree of staining reactivity with Canavalia ensiformis
      (ConA) decreased, whereas staining with Ulex europaeus agglutinin-I (UEA-I),
      Arachis hypoga (PNA) with neuraminidase pretreatment and Triticum vulgaris (WGA)
      intensified, indicating an enhanced fucosylation as well as sialylation. Goblet
      cells were stained with UEA-I, WGA, PNA and PNA with neuraminidase pretreatment,
      but scarcely with ConA. Positive PNA staining of basal cells and epithelial
      secretory granules was observed in the inflamed mucosa, especially close to areas
      where goblet cell development was prolific. It was therefore assumed that basal
      cells can differentiate into goblet cells-through epithelial secretory cells
      accompanied by sialylation and/or sulphonation of their mucins. It is concluded
      that the changes in glycoconjugate expression as well as goblet cell development
      in the inflamed mucosa are of importance for both local host resistance and
      defence mechanisms against microorganisms during the early stages of the
      inflammatory process.

PMID- 9583796
TI  - Nitric oxide and parasympathetic vascular and secretory control of the dog nasal
      mucosa.
AB  - Nasal vascular and secretory responses to local intra-arterial injection of
      acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) and to electrical
      stimulation of the nasal parasympathetic nerve fibres were recorded in dogs
      anaesthetized with pentobarbital. The influence of pretreatment with atropine and
      propranolol and the nitric oxide synthetase (NOS) inhibitor Nomega-nitro-L
      arginine (L-NNA) was analysed. As a marker for NOS, NADPH-diaphorase (NADPH-d)
      histochemistry was studied in the sphenopalatine ganglion, trigeminal nerve and
      nasal mucosa. Local intra-arterial infusion of ACh and VIP evoked dose-dependent
      vasodilatation and nasal secretion which were not modified in the presence of L
      NNA. The NO donor nitroprusside induced dose-dependent vasodilatation but no
      secretion. Atropine did not reduce the vasodilatation evoked by the
      parasympathetic nerve stimulation, but did reduce the secretory response by 55%
      (p < 0.05). During L-NNA infusion, the atropine-resistant vasodilatation evoked
      by parasympathetic nerve stimulation was reduced by a further 80% (p < 0.01) and
      the non-cholinergic secretory response was reduced by a further 30% (p < 0.05).
      Simultaneous infusion of the NO donor nitroprusside reversed the secretory
      response but not the vasodilator response to parasympathetic nerve stimulation.
      Histochemical studies revealed that NADPH-d activity was co-localized with VIP in
      parasympathetic axons. These observations suggest that NO could act as a non
      cholinergic parasympathetic neurotransmitter in the vascular and secretory
      control of the dog nasal mucosa.

PMID- 9583797
TI  - Acute pharyngotonsillitis is an infection restricted to the crypt and surface
      secretion.
AB  - A commonly accepted hypothesis is that acute pharyngotonsillitis is caused by
      bacteria which first adhere to the epithelial surface and then invade the
      tonsillar parenchyma; however, evidence directly supporting this hypothesis is
      not available. In previous studies on acute pharyngotonsillitis, we found that
      the secretion in crypts and at the surface was infected in acute
      pharyngotonsillitis while no bacteria were detected in the parenchyma. Based on
      these results, we have proposed a new hypothesis stating that the infection is
      restricted to the crypt and surface secretions in acute pharyngotonsillitis. To
      evaluate this hypothesis further, in the present study we examined tonsillar
      tissue and secretion from patients with acute pharyngotonsillitis, recurrent
      pharyngotonsillitis and healthy tonsils. Surface secretion was studied after
      sampling by an imprint technique followed by routine histological preparation.
      Tonsillar tissue was examined by fluorescence microscopy after staining with
      acridine orange and by transmission electron microscopy. There were high numbers
      of bacteria and moderate or extensive ongoing phagocytosis in the crypt and
      surface secretion from patients with acute pharyngotonsillitis. Bacteria,
      leucocytes and phagocytosis were also present, but to less extent in the
      secretion from patients with recurrent pharyngotonsillitis and to even less
      extent in the healthy controls. In none of all the investigated tonsils were
      bacteria present in the parenchyma. Bacterial adherence to the epithelial surface
      was only very rarely observed. This study supports the hypothesis that acute
      pharyngotonsillitis is an infection restricted to the crypt and surface secretion
      and that bacterial adherence is not of significant importance in the pathogenesis
      of acute pharyngotonsillitis.

PMID- 9583798
TI  - Histochemical study of the canine inferior pharyngeal constrictor muscle:
      implications for its function.
AB  - The inferior pharyngeal constrictor muscle (IPC), which consists of the
      thyropharyngeal (TP) and cricopharyngeal (CP) muscles. plays an important role
      during deglutition. The histochemical properties of the canine IPC muscle were
      investigated. The motor endplates of the TP muscle clustered at the midlength of
      the muscle, while those of the CP muscle were scattered diffusely. The glycogen
      depletion technique suggested that most of the CP muscle fibers terminated into
      the belly of the muscle and fiber lengths varied. With ATPase stain, type II
      fibers were shown to be predominant in the TP muscle, while type I fibers were
      predominant in the CP muscle. The diameter of the TP muscle fibers was
      significantly larger than that of the CP muscle. Although the histochemical
      characteristics of these two muscles were markedly different, they gradually
      changed, resulting in their coordinated physiological movements.

PMID- 9583799
TI  - Preservation of tubal function in patients with nasopharyngeal carcinoma, post
      irradiation.
AB  - Nineteen nasopharyngeal carcinoma (NPC) patients were subjected to eustachian
      tube function testing before and 5 years after irradiation. Tubal patency and
      clearance function of the eustachian tube showed deterioration if maximum
      irradiation dosage was more than 70 Gy, whereas dynamic function of the
      eustachian tube was preserved. Development of middle ear complications in NPC
      patients post-irradiation was caused by both tubal and inflammatory factors. To
      preserve tubal function, maximum irradiation dosage to NPC should be limited to
      70 Gy. To decrease the inflammatory reaction, firstly, middle ear effusion should
      be drained by repeated myringotomies instead of grommet insertion, and secondly,
      sinusitis should be evaluated and treated, because sinusitis can aggravate otitis
      media with effusion.

PMID- 9583800
TI  - Influence of tumour necrosis factor microsatellite polymorphisms on
      susceptibility to head and neck cancer.
AB  - While cigarette smoking and alcohol consumption are recognized covariates for
      head and neck squamous cell carcinoma (SCC), the role of genetic factors in
      determining individual susceptibility is unknown. The human tumour necrosis
      factor (TNF) region on chromosome 6p21 within the major histocompatibility
      complex (MHC) includes a number of immunologically important genes. Recently,
      five microsatellite markers have been described in the TNF locus. TNF levels vary
      with different TNF microsatellite alleles, and associations of these
      microsatellite markers with autoimmune diseases and different types of cancer
      have been shown. Therefore, the TNF locus represents candidate susceptibility
      genes for head and neck cancer. This study describes the influence of TNF a-d
      microsatellite polymorphisms on susceptibility to head and neck cancer by
      comparing the allele frequencies of 269 patients suffering from laryngeal cancer
      and 123 patients suffering from oral cavity pharyngeal cancer and 113 German
      controls. DNA was extracted from peripheral blood samples, amplified by
      polymerase chain reaction with fluorescently labelled primers for TNF
      microsatellite (a-d) and electrophoresed on polyacrylamide gels using an
      automated DNA sequencer. The data showed no differences in allele frequencies
      between controls and pharyngeal cancer patients. By contrast, the TNF b3 allele
      was associated with altered risk for laryngeal cancer (p = 0.0006, odds ratio
      2.2). Homozygosity for TNF b3/b3 resulted in an increased risk of developing
      laryngeal cancer (p = 0.004, odds ratio 5.3). Susceptibility to supraglottic SCC
      and multiple primary tumours was mediated by the absence of the a11 allele. The
      data provide the first evidence that allelism at the TNF microsatellite markers
      alter the risk of developing SCC of the larynx.

PMID- 9583801
TI  - HLA class I region sequences, 1998.

PMID- 9583802
TI  - HLA class II region sequences, 1998.

PMID- 9583803
TI  - Characterization of the ABO blood group genes in macaques: evidence for
      convergent evolution.
AB  - The ABO blood group system is known to act as a major transplantation barrier in
      primates. Different primate species share the presence of A and B antigens. The
      polymorphism of the macaque ABO blood group genes was analyzed by cloning and
      sequencing the exon 7 region. In the case of the rhesus macaque (Macaca mulatta)
      and cynomolgus monkey (Macaca fascicularis) we were able to identify ABO blood
      group gene segments which cluster into two lineages, namely: *A/*O1 and *B. In
      addition allelic variation was observed. The 2 amino acid replacements at
      positions 266 and 268, which are thought to be crucial for A or B transferase
      activity, could be confirmed for both macaque species. Comparison of primate
      sequences shows that A and B reactivity was generated independently from each
      other in the hominoids and Old World monkey lineages. Hence, the primate A and B
      blood group genes are subject to convergent evolution.

PMID- 9583805
TI  - Twenty-six new polymorphic microsatellite markers around the HLA-B, -C and -E
      loci in the human MHC class I region.
AB  - The human major histocompatibility complex (MHC) class I region is believed to
      contain a large number of disease-related loci for diseases such as Behcet's
      disease and psoriasis vulgaris. Although many novel genes have recently been
      identified in this region, it still appears to be difficult to relate any of
      these new genes to MHC class I-associated diseases as causative genetic factors.
      During the course of large-scale genomic sequencing of the human MHC class I
      region, we identified 262 microsatellite sequences with dinucleotide to
      pentanucleotide repeats around the HLA-B, -C and HLA-E genes. Of these, 26
      microsatellites were investigated for repeat polymorphism using 60 HLA homozygous
      B-cell lines and 60 healthy random individuals. The average number of alleles at
      these microsatellite loci was 9.6 with a PIC (polymorphism content value) of
      0.69. These new polymorphic microsatellite markers will probably be very useful
      for precise mapping of disease-related genes within the HLA class I region in
      linkage analysis. Moreover, they will provide a powerful tool to study
      recombination events in this region, which contributes to haplotypic
      diversification.

PMID- 9583804
TI  - HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo
      populations.
AB  - HLA class II alleles were identified in 181 healthy unrelated Ethiopian children
      of both sexes and in 350 European controls from the South of France. The
      Ethiopian individuals belonged to the two major ethnic groups of the country:
      Oromo (N=83) and Amhara (N=98). In both panels, genetic polymorphism of HLA class
      II alleles was analysed for the first time by molecular typing of DRB1, DQA1 and
      DQB1 loci. Allelic and phenotypic frequencies were compared with those of
      European controls and other African populations. Construction of HLA class II
      three-locus haplotypes was also performed. The study revealed some differences
      between the two groups. Characteristic features of Central and North African
      populations appeared on the Ethiopian HLA genotypes. Surprisingly, DRB1*11
      presented one of the lowest gene frequencies in both Ethiopian ethnic groups in
      contrast to Europeans and West Africans. Furthermore, this decrease was more
      marked than those observed using serological techniques in other geographically
      close East African countries. Oromo and Amhara only showed minor differences in
      spite of their different origins and histories. One significant difference
      consisted of a lower DRB1*01 gene frequency in Oromo as reported in most West
      African people. Some new or rare haplotypes were also observed in the Oromo
      group. Our results underline the distinctive features of the Ethiopian
      populations among the few HLA genotyping data available for East African groups
      and emphasise the major interest of such investigations in this region of Africa.

PMID- 9583806
TI  - HLA haplotypes in Koreans based on 107 families.
AB  - There are marked differences in the distribution of HLA haplotypes among
      different populations, and multilocus HLA haplotypes can best be studied by
      family analysis. In the present study, 107 Korean families were analyzed for HLA
      A, B, C, DR, and DQ antigens and haplotypes. Allele frequencies of more than 10%
      for class I antigens were A2, A24, A33, B44, B62, Cwl, Cw7, Cw9, Cw10, and C
      blank (CBL) and those for class II antigens were DR4, DR8, DR13, DR15, DQ1, DQ3,
      DQ4 and DQ7. In the analysis of HLA haplotypes, 18 kinds of A-B-DR and 11 kinds
      of A-C-B-DR-DQ haplotypes occurred at frequencies of more than 1%, comprising 34%
      and 24% of the total theoretical haplotypes, respectively. The five most common A
      B-DR haplotypes were exclusively related with the five most common A-C-B-DR-DQ
      haplotypes (frequency>2%). These remarkably conserved five-locus haplotypes in
      Koreans were A33-CBL-B44-DR13-DQ1 (5.4%), A24-Cw7-B7-DR1-DQ1 (3.5%), A33-Cw7-B44
      DR7-DQ2 (3.0%), A33-Cw10-B58-DR13-DQ1 (2.3%), and A30-Cw6-B13-DR7-DQ2 (2.3%).
      Comparison of the distribution of A-B-DR haplotypes among East Asian populations
      revealed that Koreans are closest to Japanese, but show a higher degree of
      polymorphism in the distribution of HLA haplotypes compared to Japanese. The
      results obtained in this study will be useful as basic data on Koreans for
      anthropology and organ transplantation.

PMID- 9583807
TI  - Diversity of HLA-B61 alleles and haplotypes in East Asians and Spanish Gypsies.
AB  - The distribution of HLA-B61 alleles and their association with HLA-C and DRB1
      alleles were investigated in six East Asian populations (South Korean, Chinese
      Korean, Man (Manchu), Northern Han, Mongolian and Buryat) and Spanish Gypsies and
      compared to our previous report on the Japanese population. The alleles were
      identified using a group-specific polymerase chain reaction (PCR) and genomic DNA
      followed by hybridization with sequence-specific oligonucleotide probes (SSOP).
      Both HLA-B*4002 and B*4006 were commonly detected in the South Korean, Chinese
      Korean, Man, Northern Han and Japanese populations, while HLA-B*4002 was
      predominant in the Mongolian and Buryat populations. Strong associations of
      B*4002 with Cw*0304 and of B*4006 with Cw*0801 were commonly observed in these
      East Asian populations. In contrast, in Spanish Gypsies, only HLA-B*4006 was
      found and the allele exhibited a strong association with Cw*1502. HLA-B*4003 was
      also identified in the South Korean, Chinese Korean, Northern Han, Mongolian and
      Japanese populations at relatively low frequencies, and exhibited an association
      with Cw*0304. Moreover, the association of these B61 alleles with the DRB1
      alleles revealed considerable diversity among the different populations. HLA
      B*4004 and B*4009 were not observed in these populations. Consequently, the
      frequencies of the B61 alleles varied among the different East Asian populations,
      but the individual B61 alleles were carried by specific haplotypes often
      regardless of the ethnic differences.

PMID- 9583808
TI  - DQA-DQB linkage in Old World monkeys.
AB  - The MHC DQ region in nonhuman primates, as in humans, consists of alpha and beta
      chains that are polymorphic with strong linkage disequilibrium between certain
      DQA-DQB alleles. Not only are contemporary HLA class II allelic variants present
      in evolutionarily distant species, but we demonstrate that linkages between loci
      also bear ancient roots. In unrelated baboons (Papio cynocephalus anubis) and
      family segregation analysis of pigtailed macaques (Macaca nemestrina) we found
      cis-linkages between DQA1*01 and DQB1*05 or *06, between DQA1*05 and DQB1*03, and
      between DQA1*03 and DQB1*03 alleles, all of which are also prominent in modern
      humans. In contrast, one linkage that has not been seen in humans, between
      DQA1*05 and DQB1*06 alleles, was also found. These patterns of selective linkage
      disequilibrium imply evolutionary mechanisms following the divergence of species
      that constrain the diversity of haplotypes which evolve.

PMID- 9583809
TI  - Polymorphism analysis of four canine MHC class I genes.
AB  - We have studied the variability of four structurally complete dog leukocyte
      antigen (DLA) class I genes, termed DLA-12, -88, -79 and -64, in a population of
      mixed breed, unrelated dogs. The human HLA and canine DLA loci share a high
      degree of similarity in terms of gene structure. This analysis focused on the
      first three exons of each of four complete canine genes. Exons two and three are
      the major source of polymorphism in the corresponding human genes. In this
      analysis, DLA-88 was found to be significantly more polymorphic than the other
      three genes, with 44 distinct alleles observed among 63 mixed breed, unrelated
      dogs. The remaining genes had between one and four alleles when examined in 25
      dogs. This work was carried out as part of an effort to develop an MHC typing
      system for the dog, which is critical to the further development of preclinical
      studies of hematopoietic stem cell and solid organ transplantation in the canine
      model.

PMID- 9583810
TI  - HSP70 gene polymorphisms in ankylosing spondylitis.
AB  - Despite the strength of the association of ankylosing spondylitis (AS) with HLA
      B27, other genetic elements could play a possible role in the pathophysiology of
      AS. Because of the localization, in the proximity of the HLA-B locus, and the
      involvement of heat shock proteins (HSP) in the immune response, we analyzed the
      influence of HSP70 gene polymorphism on the susceptibility to AS. HSP70-1, HSP70
      2 and HSP70-hom genotypes were analyzed by PCR-RFLP in patients with AS and in
      healthy controls. The results obtained in the present study showed that there are
      not significant differences in the distribution of HSP70-hom genotypes, whereas
      significant differences in HSP70-1 and HSP70-2 genotypes between AS patients and
      random controls were found. However, when the distribution of these genotypes
      were compared in B*27-matched AS patients and controls, the differences
      disappeared. These data suggest that the polymorphism of HSP70 genes was not
      independently associated with AS, and that the differences in HSP70-1 and HSP70-2
      genotypes among AS patients and controls appears to be due to the linkage
      disequilibrium between HSP70 alleles and HLA-B*27.

PMID- 9583811
TI  - Tumor necrosis factor gene polymorphisms in ankylosing spondylitis.
AB  - Despite the strength of the association of ankylosing spondylitis (AS) with HLA
      B27, other genetic elements could play a possible role in the pathophysiology of
      AS. In view of its gene location, in the proximity of the HLA-B locus, and
      biological effects, tumor necrosis factor (TNF) genes are potential candidates
      for additive susceptibility factors to AS. TNFalpha and TNFbeta genotypes were
      analyzed by PCR-RFLP in 57 patients with AS, 102 random controls and 30 HLA-B*27
      positive controls. No significant differences of TNFalpha promoter variations at
      position -308 and -238 were found in AS patients in comparison with controls. The
      -244 polymorphism was not detected in our population. The TNFbeta genotype
      frequency was significantly different between AS patients and random controls.
      However, when the distribution of the TNFbeta genotype was compared in B*27
      positive AS patients and controls, these differences disappeared. In addition, we
      demonstrated that the TNFbeta*1 was in strong linkage disequilibrium with the
      B*27 allele, which may explain the differences observed for the TNFbeta genotype
      among AS patients and random controls. Our data suggest that the polymorphisms of
      TNFalpha and TNFbeta genes do not have an independent effect on AS
      susceptibility.

PMID- 9583812
TI  - Distribution of human platelet antigens in a Chinese population.
AB  - We report the distribution of the human platelet antigens HPA-1, -2, -3, -4 and 
      5 as determined using the polymerase chain reaction with sequence-specific
      primers in 100 random, healthy Chinese in Hong Kong. The HPA-1a, -2a, -4a and -5a
      genes were present in every sample tested, HPA-1b, -2b and -5b were rare, and the
      sample was monomorphic for HPA-4a. HPA-3a and -3b genes showed frequencies of
      0.525 and 0.475 respectively. There was no departure from Hardy-Weinberg
      equilibrium in any of the five HPA systems studied.

PMID- 9583813
TI  - Complete coding sequence of HLA-B*2712: a serologic B27-negative antigen
      associated to Bw6.
AB  - We report the complete coding sequence of a new HLA-B27 subtype, B*2712, which
      was found in a Caucasian Spanish family within the chromosome A2-Cw2-B*2712-DR15
      DQ6. B*2712 was first detected as a segregating B blank Bw6-associated antigen.
      Extensive serologic analysis demonstrated that this new B27 subtype was not
      recognised by any of the B27-monospecific antibodies, giving positive reactions
      only with some monoclonal reagents against B40 or B27,40. Sequencing analysis
      showed a high similarity with B*2708, only differing in three clustered amino
      acid residues at positions 69 to 71 located in the alpha helix of the alpha1
      domain. Residues 69 and 71 point towards the T-cell receptor, while amino acid 70
      points to the antigen binding site. Loss of the conserved structure of pocket B
      as well as the differentiated pocket F configuration suggests that B*2712 does
      not confer ankylosing spondylitis susceptibility. Misleading serologic definition
      supports the usefulness of DNA-typing methods to complement HLA class I typing.

PMID- 9583814
TI  - Nucleotide and amino acid sequence alignment for human killer cell inhibitory
      receptors (KIR), 1998.
AB  - We present alignments of nucleotide sequences and deduced amino acid sequences
      for all currently identified killer cell inhibitory receptors (KIR). The genes
      for these receptors have been localized to human chromosome 19q13.4 and
      constitute a large gene family. They all encode structures typical of type I
      transmembrane molecules belonging to the immunoglobulin superfamily (Ig-SF).
      Extensive polymorphism exists within the genes and many of the currently
      identified cDNA clones represent alternatively spliced forms of previously
      reported full-length clones. The sequence alignments have been posted on the
      World Wide Web and are accessible at the Tissue Antigens web site at:
      http://www.tissue-antigens.dk/kir-align.html. The alignments will be updated at
      intervals.

PMID- 9583815
TI  - Anatomic repair of corrected transposition or atrio-ventricular discordance:
      report of 8 cases.
AB  - BACKGROUND: It is well recognized that a right ventricle (RV) may eventually fail
      if working as systemic. This has led to arterial switch operation for
      transposition of the great arteries (TGA), but more recently to anatomic
      correction of 'corrected transposition' or atrio-ventricular discordance (AVD)
      combining an atrial switch and a ventricular outflow repair (arterial switch or
      Rastelli type). METHODS: We report here 8 cases of such anatomic correction of
      AVD in patients from 3 months to 10 years. Of these patients, 6 had situs
      solitus, and 2 situs inversus; 7 patients had a ventricular septal defect (VSD);
      5 had an increased pulmonary flow, and 3 had a decreased pulmonary flow with
      pulmonary stenosis (PS) or pulmonary atresia (PA). In all, 6 had discordant and 1
      had concordant ventriculo-arterial (VA) relations, and 1 had double-outlet RV, 2
      had an associated coarctation, and 1 had a cor triatriatum. Of the 8 patients, 5
      had pulmonary artery hypertension, 3 a moderate to severe tricuspid insufficiency
      and 6 had undergone one or more previous operations. Correction was done between
      3 months and 10 years of age, with 7 having a Senning procedure (twice left
      sided) and 1 a Mustard type operation. VA outflows were repaired with: 4 arterial
      switches, 1 left ventricle to aorta rerouting, 1 right ventricular outflow tract
      (RVOT) repair and 2 Rastelli. A tricuspid annuloplasty was done once. RESULTS:
      All patients survived the operation, but 2 patients needed a reoperation (both
      successful): late obstruction of pulmonary venous channel after a left-sided
      Senning, and residual VSD closure. Mean follow-up is 45 months (3-122). Of the 8
      patients, 6 patients are in sinus rhythm, 2 have junctional rhythm. A patient
      with junctional rhythm and occasional tachycardia died suddenly 18 months after
      surgery 1 week after satisfactory evaluation. All have a normal left ventricle
      function as evidenced by echocardiography. CONCLUSIONS: Despite a more demanding
      procedure, the 'anatomic repair' of hearts with AVD is possible, even in infancy,
      with good early and mid-term result. Despite the potential late rhythmic problems
      of the Senning operation (somehow more frequent with AVD in our experience), it
      may become, with increasing experience, the procedure of choice in corrected
      transposition.

PMID- 9583816
TI  - Cerebral effects of aortic clamping during coarctation repair in children: a
      transcranial Doppler study.
AB  - OBJECTIVE: Haemodynamic changes as a consequence of application and release of
      aortic clamps for surgical repair of aortic coarctation are compensated by
      cerebrovascular autoregulation. Transcranial Doppler was used to study the effect
      of these haemodynamic changes upon brain circulation in children during aortic
      coarctation repair. METHOD: A 2-MHz transcranial Doppler system continuously
      recorded mean cerebral blood flow velocities from the left middle cerebral artery
      in 13 children (aged from 5 days to 14 years) during repair of their coarctation.
      Measurements were performed: prior to aortic clamping (baseline); during the
      first 5 min after clamp application; 1 min before declamping; at 1, 2, 4 and 6
      min after the release of both proximal and distal aortic clamps; and at initial
      chest closure. A contralateral upper-limb non-invasive blood pressure cuff
      measured systemic blood pressures. Haemodynamic and anaesthetic parameters were
      monitored. Patients were stratified by age into two groups: age < 6 months (group
      A) and age > 6 months (group B). RESULTS: With aortic clamping, systemic blood
      pressures (range from: -16 to +54%) and cerebral blood flow velocities (range
      from -40 to +19%) changed slightly (P > 0.05) from initiation to end of aortic
      clamping. In group A, release of aortic clamps resulted in moderate fluctuations
      in systemic blood pressures (range from -34 to +15%) (P > 0.05) and a marked
      reduction in cerebral blood flow velocities (range from -63 to -33%) (P < 0.01).
      At the time of surgical closure, flow velocities had improved in all infants
      except one. Group B did not show major reductions in either cerebral blood flow
      velocity or systemic blood pressures throughout all measurements (P > 0.05).
      During aortic clamp release, young infants responded with lower brain blood flow
      velocities as compared to older children (r = 0.68; P < 0.05). CONCLUSION:
      Transient central nervous system hypotension results as a consequence of flow
      redistribution during aortic declamping in young infants. Older children usually
      show a faster autoregulatory compensation to these haemodynamic changes. The
      observed age-related physiologic differences, suggest that young infants may
      require higher systemic blood pressures during declamping to prevent the cerebral
      blood flow reduction. Transcranial Doppler appears to be a valuable monitor of
      these cerebral haemodynamic changes.

PMID- 9583817
TI  - Centrifugal ventricular assist in children under 6 kg.
AB  - OBJECTIVE: The clinical application of centrifugal ventricular assist devices
      (VAD) has generally been limited to adults and large paediatric patients. In our
      experience neonates and small paediatric patients requiring ventricular support
      post-cardiopulmonary bypass are well supported by VAD. In this study we analyse
      our experience. METHODS: We have examined the records of our VAD patients who
      weighed less than 6 kg. Thirty-four patients, ranging in age from 2 to 258 days
      (median 60 days) and weight from 1.9 to 5.98 kg (median 3.7 kg), underwent 35 VAD
      procedures. One patient was supported on VAD twice. RESULTS: All patients had
      congenital heart lesions and were placed on VAD either because they could not be
      weaned from cardiopulmonary bypass after repair or palliation of the lesion
      (71.5%), or for support in the post-operative period due to refractory low
      cardiac output (28.5%). Twenty-two of the 35 VAD procedures (0.63, 95% CI: 0.45
      0.78) resulted in successful weaning and decannulation, this was similar to the
      weaning probability for patients greater than 6 kg (P = 0.07). There were 10 late
      deaths in this group, with a 1-year KM survival of 0.31 (95% CI: 0.17-0.47). Most
      late deaths were related to irreversible cardiac disease processes as were the
      elective discontinuance of VAD outcomes. Neither weight, age, VAD duration, CPB
      duration, X clamp duration, univentricular anatomy or TGA anatomy predicted
      successful discharge from hospital (P > 0.05)--Weight P = 0.576; Age P = 0.532;
      VAD duration P = 0.181; CBP duration P = 0.549; X clamp duration P = 0.984;
      Univentricular anatomy P = 0.481; TGA anatomy P = 0.099. CONCLUSION: We believe
      centrifugal ventricular assist is a realistic option in very small patients who
      require post-cardiopulmonary bypass support. It is relatively easy to establish
      and manage, the results, although showing no factors predictive of successful
      discharge, are encouraging.

PMID- 9583818
TI  - Mitral valve replacement with glutaraldehyde preserved aortic allografts.
AB  - OBJECTIVE: To present long-term results after mitral valve replacement with stent
      mounted glutaraldehyde preserved aortic allografts in patients older than 15
      years. The clinical support for this study was to combine the glutaraldehyde
      technique of biological tissue preservation with the advantages of allografts
      when compared to xenografts. This was demonstrated in previous studies using
      other methods of tissue processing. METHODS: Between September 1984 and November
      1994, 70 patients aged 16-77 years (mean 35.4 years) underwent mitral valve
      replacement with this preserved and mounted allograft. Of these, 40 patients
      (57.2%) were aged 16-35 years and 15 (21.4%) were 20 years old or younger; 46
      (65.7%) were females and 24 (34.3%) males. Single mitral valve replacement was
      performed in 60 patients and 10 were also subjected to other combined cardiac
      procedures. Human aortic valves were obtained during routine autopsy, processed
      in glutaraldehyde and mounted into flexible stents, using the same technique as
      that used for porcine bioprostheses. RESULTS: Hospital mortality was 1.4%. Total
      follow-up was 543.1 patient-years, corresponding to a mean follow-up of 7.9 years
      per patient. Echocardiography demonstrated a hemodynamic performance similar to
      porcine bioprostheses. Late mortality was 0.7 +/- 0.6% per patient-year and the
      causes were congestive heart failure in 2, prosthetic endocarditis in 1 and acute
      myocardial infarction in 1. The 12-year actuarial survival was 92.4 +/- 3.2%. The
      incidence of late complications was 5.2 +/- 1.2% per patient-year, including
      congestive heart failure, prosthetic endocarditis, periprosthetic leak,
      thromboembolic episodes, recurrence of rheumatic disease, coronary artery disease
      and allograft failure. Complications related to heart disease represented 2.8 +/-
      0.6% and allobioprosthesis-related 2.4 +/- 0.5% per patient-year. The 12-year
      actuarial freedom from primary valve failure was 81.0 +/- 15.0%. The incidence of
      reoperations was 1.5 +/- 0.8% per patient-year and the main indication was
      prosthetic endocarditis. Other causes were periprosthetic leak, aortic
      insufficiency in the native aortic valve and allobioprosthesis dysfunction.
      Functional results demonstrated a significant improvement in patients clinical
      condition. CONCLUSION: This 12-year follow-up shows a very low incidence of
      primary allograft failure for patients older than 15 years undergoing mitral
      valve replacement, and much superior than our results with porcine bioprosthesis
      in the same age group. This supports our assumption that this investigational
      valve represents a new advance in cardiac valve surgery.

PMID- 9583819
TI  - Composite graft replacement of the aortic root in acute dissection.
AB  - OBJECTIVE: In acute type A dissection the indication for composite graft
      replacement of the aortic root and the optimal implantation technique are a
      matter of debate. In this study early and late results of root replacement in
      acute dissection are determined and compared with supracoronary graft
      replacement. Two implantation techniques (open vs. inclusion) are evaluated.
      METHODS: Between 1985 and 1995, 207 consecutive patients (mean age 58 +/- 12
      years, 78% men) were operated for acute type A dissection of the aorta. Root
      replacement in 50 patients (inclusion technique in 34/50 patients with Cabrol
      shunt in 15/34 patients, open technique in 16/50 patients) was compared with more
      conservative procedures in 157 patients: supracoronary graft replacement in 143
      patients (with aortic valve replacement in 23 patients) and local repair without
      graft interposition in 14 patients. Preoperative risk factors, like hemodynamic
      instability, renal failure, neurologic disorder and coronary artery disease did
      not differ in the two treatment groups. RESULTS: Early results, survival and
      reoperation-free survival after 5 years were insignificantly better after root
      replacement: mortality 10/50 (20%) vs. 38/157 (24%) P = n.s.; hemorrhage 10/50
      (20%) vs. 39/157 (25%) P = n.s.; stroke 5/50 (10%) vs. 27/157 (17%) P = n.s.;
      survival 70 +/- 7% vs. 63 +/- 4%, reoperation free survival 92 +/- 6% vs. 78 +/-
      5% P = 0.0815). For the open technique, early mortality was 18.8 vs. 20.6%, P =
      n.s. and reoperation free survival at 5 years was 80.7 vs. 65.2%, P = n.s.
      Perioperative complications did not differ in the two technical groups and a
      single pseudoaneurysm occurred in the Bentall group. CONCLUSION: In acute
      dissection composite graft replacement of the aortic root can be carried out with
      good early and late results not inferior to more conservative procedures. The
      open technique is the implantation method of choice and the modified Bentall
      technique is indicated in situations with increased risk of bleeding.

PMID- 9583821
TI  - Tissue engineering: a new approach in cardiovascular surgery: Seeding of human
      fibroblasts followed by human endothelial cells on resorbable mesh.
AB  - OBJECTIVE: In tissue engineering the material properties of synthetic compounds
      are chosen to enable delivery of dissociated cells onto a scaffold in a manner
      that will result in in vitro formation of a new functional tissue. The seeding of
      human fibroblasts followed by human endothelial cells on resorbable mesh is a
      precondition of a successful creation of human tissues such as vessels or cardiac
      valves. METHODS: Polymeric scaffolds (n = 18) composed of polyglycolic acid (PGA)
      with a fiber diameter of 12-15 microm and a polymer density of 70 mg/ml were used
      as square sheets of 1 x 1 x 0.3 cm. Fibroblasts (passage 7) harvested from human
      foreskin were seeded (3.4 x 10(6)) and cultured over a 3 week period on a PGA
      mesh, followed by seeding of endothelial cells (passage 5, 2.8 x 10(6)) harvested
      from human ascending aorta. Thereafter the new tissue was stained for HE, van
      Gieson, Trichrom Masson, Factor VIII and CD 34 and proved by scanning electron
      microscopy. RESULTS: Microscopic examination of the seeded mesh demonstrated that
      the human fibroblasts were attached to the polymeric fibers and had begun to
      spread out and divide. The scanning electron microscopic examination demonstrated
      a homogeneous scaffold resembling a solid sheet of tissue. The seeded endothelial
      cells formed a monolayer on the fibroblasts and no endothelial cell invasion or
      new formation of capillaris could be detected. CONCLUSIONS: These results are a
      first step to demonstrate that seeding of human fibroblasts and endothelial cells
      on PGA-mesh might be a feasible model to construct human tissues such as vessels
      or cardiac valves.

PMID- 9583820
TI  - Multiple mechanical valve replacement surgery comparison of St. Jude Medical and
      CarboMedics prostheses.
AB  - OBJECTIVE: The experience with the St. Jude Medical (SJM) and CarboMedics (CM)
      bileaflet mechanical prostheses was evaluated to determine thromboembolic and
      hemorrhagic complications and predictive risk factors. METHODS: From 1989 to
      1994, a total of 246 patients had multiple valve replacement (SJM, 140; CM, 106);
      concomitant procedures 20.3% (50) [coronary artery bypass 10.6% (26)] and 53.7%
      (132) previous cardiac surgery, primarily valve replacement procedures. The pre
      operative variables [coronary artery disease, previous cardiovascular surgery,
      concomitant procedures, valve lesion (except mitral stenosis), status, atrial
      fibrillation, and NYHA III/IV] did not distinguish the prosthesis-type (pNS).
      RESULTS: The prosthesis-type and the pre-operative variables, including atrial
      fibrillation, were not predictive of overall thromboembolism (TE). The linearized
      rate of total TE events for overall multiple replacements (MR) was 5.4%/patient
      year (minor, 2.52; major 2.85); the total TE for CM and SJM was 5.4%/patient
      year, respectively. The < or = 30 day major TE crude rate was 0.82%, while the >
      30 day major event rate was 2.7%/patient-year. Of the total (major and minor) TE
      events 100% (3) of < or = 30 days and 72% (29), > 30 days had an INR < 2.5 at or
      immediately prior to the event. The thrombosis rate (included in total TE events)
      was 0.67%/patient-year (4 events, 100% INR < 2.5). Of the various TE event
      categories the prosthesis-types (CM and SJM) were not differentiated (pNS). The
      freedom, at 5 years, from major/fatal TE, thrombosis and hemorrhage from
      anticoagulation was 89.3 +/- 3.8% for CM and 87.9 +/- 3.7% for SJM and, 91.3 +/-
      3.5% and 89.3 +/- 3.7%, respectively, (pNS) exclusive of early events.
      CONCLUSIONS: The performance of the CarboMedics and St. Jude Medical prostheses
      in multiple valve replacement surgery in this non-randomized prospective study
      revealed no significant differences in performance with regard to thromboembolic
      and hemorrhagic complications.

PMID- 9583822
TI  - Pericardial effusion and AIDS: benefits of surgical drainage.
AB  - OBJECTIVES: During the last few years, AIDS has been the main cause of large
      pericardial effusions in urban settings. We have therefore had to perform
      surgical pericardial drainage for diagnostic and/or therapeutic purposes in AIDS
      patients. This study was designed to establish the diagnostic and therapeutic
      yield of pericardial drainage for these patients. METHODS: We retrospectively
      reviewed the data of the 13 AIDS patients with a pericardial effusion, referred
      to our surgical department between December 1989 and December 1996 for surgical
      drainage and pericardial biopsy. RESULTS: Cytological studies and searches for
      bacteria, mycobacteria and parasites were all negative. The histology of the 13
      pericardial biopsies disclosed three pericardial locations of a Kaposi's sarcoma
      (all three patients had a pre-existent extra-cardiac location of this sarcoma)
      and one pericardial location of an already known immature mediastinal teratoma.
      In the nine other cases, the lesions were aspecific. Four patients died of
      multivisceral failure within 30 days of surgery. For the survivors, surgical
      drainage afforded relief and there were no clinical signs of recurrent effusion.
      CONCLUSIONS: The cause of pericardial effusion in AIDS is still often unknown,
      even after pericardial biopsy. Here, aspecific pericarditis was the most common
      diagnosis. Although the prognosis of such effusion in these patients is known to
      be poor, surgical drainage provided relief for those who survived the post
      operative period.

PMID- 9583823
TI  - Transmyocardial laser revascularisation in acutely ischaemic myocardium.
AB  - OBJECTIVE: Although recent experience suggests that transmyocardial laser
      revascularisation (TMLR) relieves angina, its mechanism of action remains
      undefined. We examined its functional effects and analysed its morphological
      features in an animal model of acute ischaemia. METHODS: A total of 15 pigs were
      randomised to ligation of left marginal arteries (infarction group, n = 5), to
      TMLR of the left lateral wall using a holmium:yttrium-aluminium garnet (Ho:YAG)
      laser (laser group, n = 5), and to both (laser-infarction group, n = 5). All the
      animals were sacrificed 1 month after the procedure. Haemodynamics and
      echocardiography with segmental wall motion score were carried out at both time
      intervals (scale 0-3: 0, normal; 1, hypokinesia; 2, akinesia; 3, dyskinesia).
      Histology of the involved area was analysed. RESULTS: Laser group showed no
      change of the segmental wall motion score of the involved area 30 min after the
      laser channels were made (score: 0 +/- 0). Infarction and laser infarction groups
      both showed a persistent and definitive increase of the segmental wall motion
      score (at 30 min: 1.6 +/- 0.3 and 2 +/- 0, respectively; at 1 month: 1.8 +/- 0.2
      and 1.8 +/- 0.4, respectively). These increases were all statistically
      significant in comparison with baseline values (P < 0.5), however comparison
      between infarction and laser-infarction groups showed no significant difference.
      On macroscopic examination of the endocardial surface, no channel was opened. On
      histology, there were signs of neovascularisation around the channels in the
      laser group, whereas in the laser-infarction group the channels were embedded in
      the infarction scar. CONCLUSIONS: In this acute pig model, TMLR did not provide
      improvement of contractility of the ischaemic myocardium. To the degree that the
      present study pertains to the clinical setting, the results suggest that
      mechanisms other than blood flow through the channels should be considered, such
      as a laser-induced triggering of neovascularisation or neural destruction.

PMID- 9583824
TI  - Interruption of bronchial circulation leads to a severe decrease in peribronchial
      oxygen tension in standard lung transplantation technique.
AB  - OBJECTIVE: In clinical practice lung transplantation is the only procedure where
      the transplanted organ is left without its own arterial perfusion. With the
      interruption of the bronchial arteries the nutritive support is dependent on
      collateral flow by the pulmonary artery and the oxygen tension of desaturated
      central venous blood, representing an abnormal physiology. METHODS: To analyze
      this problem systematically, we used a standard single left lung transplantation
      model in the pig (n = 12). In accordance with the clinical standard, lung
      preservation was performed with modified Euro-Collins solution with addition of
      prostacycline. The duration of ischemia was set to 4 h. Before and after single
      left lung transplantation tissue oxygen tension in the peribronchial tissue was
      measured with Licox tissue pO2 microprobes. For validation, the myocardial tissue
      oxygen tension was recorded simultaneously. The hemodynamic assessment included
      continuous flow measurement of the left and right pulmonary artery using
      Transsonic ultrasound flow probes. After transplantation the animals were
      observed for 4 h. For hypothetic augmentation of collateral blood flow to the
      peribronchial tissue we administered Nitric oxide (10 ppm) to the ventilation in
      six pigs (group B). Six pigs (group A) served as a control without the addition
      of nitric oxide (NO). All pigs were ventilated with a FiO2 of 0.5 resulting in
      paO2 values between 160 and 200 mmHg. RESULTS: In both groups single lung
      transplantation led to a significant decrease in peribronchial tissue oxygen
      tension throughout the observation period. Pre-Tx values of peribronchial tissue
      oxygen tension (38.31 +/- 6.56 mmHg) decreased to 9.72 +/- 2.55 mmHg in group A
      and 10.3 +/- 3.61 mmHg in group B after 4 h, which could not be altered by a FiO2
      of 1.0 (P < 0.0001). The addition of NO in group B led to a significantly
      augmented flow in the left pulmonary artery (0.63 +/- 0.31 l/min in group B vs.
      0.46 +/- 0.26 l/min group A, P < 0.001) representing 67 vs. 49% of the pre-Tx
      flow in groups B and A, respectively, but the peribronchial tissue oxygen tension
      was not influenced (P > 0.05). In both groups A and B, the central venous pO2 did
      not differ in the postoperative period (41.83 +/- 3.27 mmHg group A vs. 43.26 +/-
      2.98 mmHg group B) and was kept in a comparable range to the pretransplantation
      values (45.23 +/- 3.41 mmHg pre-Tx). CONCLUSIONS: The persistence of a very low
      peribronchial tissue oxygen tension in the early phase after lung transplantation
      cannot be influenced by improved pulmonary artery flow and solely relates to the
      central venous pO2, which cannot be augmented by the addition of NO. This
      mechanism might be a trigger for anastomotic healing problems, infectious
      complications and later development of obliterative bronchiolitis (OB).

PMID- 9583825
TI  - Gastric bypass for malignant esophagotracheal fistula: a series of 21 cases.
AB  - OBJECTIVE: Patients with cancer of the esophagus who develop an esophagotracheal
      fistula die within 1 month in dramatic conditions of malnutrition and asphyxia.
      We assessed the beneficial palliative effect of the Kirschner operation in the
      treatment of esophagotracheal fistula. METHODS: Between January 1980 and August
      1995, 21 patients among a continuous series of 847 with cancer of the esophagus
      developed an esophagotracheal fistula. Prior to surgery, 2 patients had an
      esophageal prosthesis followed by radio- and/or radiochemotherapy and 6 had radio
      and/or chemotherapy at curative doses. The Kirschner operation was carried out
      in all patients with exclusion of the lower end of the esophagus using a Roux-en
      Y-loop (n = 19) or ligature (n = 2). RESULTS: Within 1 month of surgery, 8
      patients (38%) died. Median length of stay in the intensive care unit and
      hospitalization was 6 days (1-30) and 17 days (3-57), respectively. Among the 13
      survivors, pulmonary infections (n = 2) and cervical fistulae (n = 5) complicated
      the postoperative period. Among the cervical fistula, 3 of them resolved
      favorably. Radio- and/or chemotherapy was given postoperatively in 7 patients
      without any improvement in survival. Among the 13 patients surviving beyond the
      postoperative period, median survival was 109 days; 7 were able to resume oral
      nutrition and quality of life was assessed as excellent in 6 of them. CONCLUSION:
      The Kirschner operation can provide a beneficial palliative effect in patients
      with an esophagotracheal fistula despite the high risk of operative mortality.
      Ideally, the Kirschner should be carried out in young patients who are still in
      good general health, before the development of respiratory complications
      compromises surgery.

PMID- 9583826
TI  - Frozen section diagnosis and surgical biopsy of lymph nodes, tumors and
      pseudotumors of the mediastinum.
AB  - OBJECTIVE: Our experience with the use of frozen section (FS) was reviewed in
      order to assess its interest and limits, during minimally aggressive mediastinal
      surgery for staging of lung carcinomas and biopsy of primary lesions. METHODS:
      The retrospective study was based on a series of 420 consecutive mediastinal
      biopsies with FS performed through cervicotomy (n = 12), mediastinoscopy (n =
      345), mediastinotomy (n = 43), manubriotomy (n = 13) or videothoracoscopy (n =
      7), in 417 patients, aged 8-86 years (mean: 52.5 +/- 15.6). The FS diagnoses were
      compared with the final diagnoses and consequences of the FS analyses were
      analyzed. RESULTS: Biopsies with FS had a 99.4% (351/353) efficiency rate for a
      precise definitive diagnosis (excluding normal lymph nodes). However, two
      patients required a second operation: one for typing a lymphoma and the other to
      correct a FS misdiagnosis of small cell carcinoma on a crushed normal lymph node.
      The sensitivity for detection of carcinoma lymph node metastases was 99%
      (200/202). The two false negative FS diagnoses, including one post-chemotherapy,
      were related to micrometastases. There were 46 correct FS diagnoses of non
      metastatic lymph node which were followed by an immediate thoracotomy during the
      same anesthesia, for benign lung lesions (n = 9) or for carcinomas (n = 37),
      including 30 lung carcinomas that were immediately resected and proved to have no
      mediastinal involvement (n = 24), or only a limited involvement in a non-biopsied
      site (n = 6). In the 51 cases of primary mediastinal tumors excluding carcinomas,
      FS indicated a resectable lesion with a sensitivity of 87.5% (7/8) and a
      specificity of 97.7% (43/44). Five lesions were immediately resected: one
      Castleman's disease, one intrathoracic goiter, two of six thymomas and a
      Hodgkin's disease, which was diagnosed as thymoma on FS. An invasive thymoma was
      resected during a second operation after a FS diagnosis of carcinoma. FS had a
      sensitivity of 100% in the 62 cases of sarcoidosis and a sensitivity of 90% in
      the 20 cases of infectious lesions. One of the 18 cases of tuberculosis and an
      infectious pseudo-tumor of the anterior mediastinum had no microbiologic study
      because of FS diagnoses of tumor necrosis and lymphoma. CONCLUSIONS: FS
      efficiently secures the adequacy of the samples and guides the surgeon's decision
      making for the resection of lung carcinomas, but is less effective for a precise
      diagnosis of some primary mediastinal lesions, which may have close histologic
      appearances.

PMID- 9583827
TI  - The role of mediastinoscopy in the diagnosis of mediastinal lymphadenopathy.
AB  - OBJECTIVE: The reported experience of axial mediastinoscopy (MDS) performed in a
      diagnostic purpose only (rather than prognostic) is limited. Therefore, we
      designated the present study to clarify morbidity, sensitivity and accuracy of
      MDS performed to diagnose various mediastinal lesions. METHODS: We prospectively
      performed 400 MDS in a diagnostic purpose on 398 patients for: (1) isolated
      mediastinal adenopathies in 271 patients (group 1), and (2) mediastinal
      adenopathies associated with a pulmonary or a hilar lesion of unknown aetiology
      in 127 patients (group 2). In group 1, most of the patients were suspected to
      have a sarcoidosis, a tuberculosis or a lymphoma. In group 2, most of the
      patients were suspected to have a lung cancer. In both groups, the other current
      diagnostic procedure usually used in each pathology had failed to give an
      accurate diagnosis. RESULTS: A total of 76% of the samples were performed in the
      right laterotracheal lymph node station, 12.5% in the lower subcarinal and
      superior subcarinal lymph node station and 7.8% in the left laterotracheal lymph
      node station. The per- and post-operative mortality rates were nil. The per
      operative morbidity accounted for six cases (1.5% of the examinations). The post
      operative morbidity accounted for three cases (0.75% of the examinations). MDS
      data radically modified the pre-operative suspected diagnosis in 74 patients
      (18.5% of the patients). There were 17 false negative results (4.3% of the
      patients). The global sensitivity of MDS was 94%, the global specificity was 100%
      and the accuracy was 95%. In group 1, the sensitivity was 96% and in group 2 it
      was 92%. CONCLUSION: According to the results, the few contraindications of the
      procedure and its low cost, we confirm that MDS is still the first choice
      procedure to diagnose lesions located in the axial mediastinum.

PMID- 9583828
TI  - Protective subpleural blanketing of intrathoracic esogastric anastomosis after
      esophagectomy.
AB  - Esophagectomy followed by intrathoracic anastomosis is threatened by leakage
      which may prove all the more serious that mediastinal contamination is extensive.
      In the technique presented, the esogastric anastomosis is slipped under the upper
      mediastinal pleura which is kept intact, after the azygos vein has been ligated
      and divided. This pleural 'blanket' may act as an efficient barrier against
      potential digestive spillage into the mediastinum.

PMID- 9583829
TI  - Sleep apnoea/hypopnoea syndrome: a potential cause of graft failure following
      heart transplantation.
AB  - A 54-year-old man presented 54 months after a successful heart transplant with
      cor pulmonale secondary to obstructive sleep apnoea/hypopnoea syndrome (SAHS).
      This unusual cause of reversible graft failure following heart transplantation is
      presented in this case report.

PMID- 9583830
TI  - Early improvement of respiratory function after surgical plication for unilateral
      diaphragmatic paralysis.
AB  - We reported an unusual case of symptomatic diaphragmatic paralysis in an elderly
      patient with progressive respiratory-dependent limitation of her daily
      activities. Surgical plication of the affected hemidiaphragm resulted in early
      clinical and physiological improvements.

PMID- 9583831
TI  - Coronary angioplasty and stenting following heart transplantation with older
      donors. Is this a rational approach?
AB  - The shortage of ideal donor hearts has led to an extension of the classical donor
      criteria of age. Higher incidence of focal coronary artery disease has been found
      in this older donor population requiring conventional angioplasty therapy. The
      authors present two patients with early coronary angiogram post transplantation,
      requiring angioplasty and stent in the lesions found.

PMID- 9583832
TI  - Preserved skeletal muscle structure with modified electrical stimulation protocol
      in a cardiomyoplasty patient: a clinico-pathological report.
AB  - Experimental and clinical studies have recently shown variable degrees of
      structural abnormalities in the transposed and chronically stimulated muscle
      graft after cardiomyoplasty procedure. The postoperative stimulation protocol of
      wrapped skeletal muscle has been claimed to be a major determinant of late
      structural derangement. Therefore, a modified stimulation protocol had been used
      after a cardiomyoplasty procedure in a 63-year-old patient. Improved
      postoperative hemodynamic data could be detected by pressure/volume analysis.
      After unexpected sudden death occurred at 15 months, autoptic examination showed
      preserved muscle structure, suggesting that a prudent stimulation protocol may
      maintain muscle viability and contribute to effective cardiac support.

PMID- 9583833
TI  - Thrombus formation of the right heart.

PMID- 9583834
TI  - Infant feeding recommendations.

PMID- 9583835
TI  - Nutritional status in cystic fibrosis: where to go from here?

PMID- 9583836
TI  - The many faces of malnutrition in Crohn disease.

PMID- 9583837
TI  - Fat distribution and insulin response in prepubertal African American and white
      children.
AB  - Ethnic differences in obesity-related disease prevalence may relate to
      differences in fat distribution or metabolism. We conducted a study in 73 African
      American and white children to examine the relation between fat distribution and
      insulin and to determine whether ethnic differences in fat distribution or in
      adiposity-insulin relations contribute to differences in insulin concentrations.
      Fasting and postchallenge insulin concentrations were determined by oral-glucose
      tolerance test, total body fat by dual-energy X-ray absorptiometry, and
      subcutaneous abdominal (SAAT) and intraabdominal (IAAT) adipose tissue by
      computerized tomography. African Americans had greater fasting insulin (x +/- SD:
      79 +/- 37 compared with 55 +/- 23 pmol/L, P < 0.01), incremental 30-min insulin
      (567 +/- 438 compared with 300 +/- 304 pmol/L, P < 0.001), and incremental area
      under the insulin curve (AUC; 262 +/- 209 compared with 164 +/- 156 pmol/L, P <
      0.01). In multiple linear regression, fasting insulin was independently related
      to total fat within both ethnic groups (model R2 = 0.42 and 0.52 for African
      Americans and whites, respectively), incremental 30-min insulin to total fat and
      IAAT in whites only (model R2 = 0.71), and AUC to SAAT in African Americans only
      (model R2 = 0.49). Adjusting insulin indexes for adiposity did not eliminate the
      significant effect of ethnicity. In general, relations between adiposity and
      insulin were stronger in whites than in African Americans. African American
      children had higher insulin concentrations than white children after total body
      fat, IAAT, and SAAT were controlled for. However, strong relations between
      adiposity (total and abdominal) and insulin in both groups suggest that obesity
      may contribute to disease risk regardless of ethnicity.

PMID- 9583838
TI  - Change in dietary saturated fat intake is correlated with change in mass of large
      low-density-lipoprotein particles in men.
AB  - We tested whether nutrient intakes estimated from 4-d diet records were
      associated with plasma lipoprotein subclasses in 103 men who were randomly
      assigned to a low-fat (24% fat) and a high-fat (46% fat) diet for 6 wk each in a
      crossover design. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase
      (HL) activities were also determined in a subset of 43 men. Changes in intake
      (ie, high fat minus low fat) of total saturated fatty acids, as well as myristic
      (14:0) and palmitic (16:0) acids, were positively correlated (P < 0.01) with
      increases in mass of large LDL particles [measured by analytic ultra
      centrifugation as mass of lipoproteins of flotation rate (Sf) 7-12] and with LDL
      peak particle diameter and flotation rate, but not with changes in LDL
      cholesterol concentration. Changes in total saturated fatty acids as well as
      myristic and palmitic acids were also inversely associated with changes in HL
      activity (P < 0.05). With the high-fat diet only, variation in dietary total
      saturated fatty acid intake was inversely correlated (P < 0.01) with
      concentrations of small, dense LDL of Sf 0-5. This correlation was significant
      specifically for myristic acid (P < 0.001). Stearic acid (18:0), monounsaturates,
      and polyunsaturates showed no significant associations with lipoprotein
      concentrations. These data indicate that a high saturated fat intake (especially
      14:0 and 16:0) is associated with increased concentrations of larger, cholesterol
      enriched LDL and this occurs in association with decreased HL activity.

PMID- 9583840
TI  - Behavioral variables and development of a central pattern of body fat from
      adolescence into adulthood in normal-weight whites: the Amsterdam Growth and
      Health Study.
AB  - Associations were investigated between the amount of physical activity, energy
      and macronutrient intake, smoking behavior, alcohol intake, and a central pattern
      of body fat (subscapular skinfold thickness and waist circumference) measured six
      times between the mean ages of 13 and 27 y in a healthy white population.
      Subjects (84 males, 98 females) were participants in the longitudinal Amsterdam
      Growth and Health Study. In longitudinal analyses, alcohol intake was positively
      associated with the subscapular skinfold thickness (beta = 0.09, 95% CI: 0.01,
      0.16) in males. In females, the subscapular skinfold thickness was negatively
      associated with physical activity (beta = -0.10. 95% CI: -0.15, -0.05) and,
      unexpectedly, energy intake (beta = -0.25, 95% CI: -0.31,-0.19), whereas a
      positive association was found with carbohydrate intake (beta = 0.09. 95% CI:
      0.02, 0.16). In both sexes, the mean value of behavioral variables, obtained from
      the mean value in adolescence and the values obtained at 21 and 27 y of age was
      not significantly associated with the subscapular skinfold thickness or waist
      circumference at the mean age of 27 y, except for a small positive association
      between physical activity and the subscapular skinfold thickness in males (R2 =
      2.3%).

PMID- 9583839
TI  - Estimating the concentration of beta-carotene required for maximal protection of
      low-density lipoproteins in women.
AB  - The reportedly inconsistent antioxidant protective effect of beta-carotene on
      plasma LDL may depend on LDL's beta-carotene concentration. We measured carbonyl
      production by CuSO4-challenged LDL from nine healthy women living at the US
      Department of Agriculture-Western Human Nutrition Research Center and consuming a
      natural food diet that provided only 0.14 micromol beta-carotene/d for 120 d.
      During the first 60 d, four women received a placebo and the remaining five women
      received too small a supplement (0.93 micromol beta-carotene/d) to increase
      plasma or LDL beta-carotene; therefore, the data for all nine women during this
      time were pooled. From days 61 to 120, all subjects received the small
      supplement. From days 101 to 120 they all received an additional, larger, mixed
      carotenoid supplement (6.16 micromol beta-carotene/d). Plasma beta-carotene
      dropped from 0.76 +/- 0.21 micromol/L (x +/- SEM) on day 2 to 0.33 +/- 0.08 on
      day 60 (P = 0.035) and rose to 1.73 +/- 0.18 (P = 0.001) on day 120. LDL beta
      carotene dropped from 1.67 +/- 0.53 micromol/g LDL protein on day 2 to 1.27 +/-
      0.28 micromol/g LDL protein on day 60 (P = 0.650) and rose to 10.04 +/- 1.07
      micromol/g LDL protein (P = 0.001) on day 120. Plasma lycopene dropped from 0.20
      micromol/L on day 2 to 0.02 micromol/L on day 60 and did not increase by day 120.
      Carbonyl production rose from 24 +/- 6 micromol/g LDL protein on day 2 to 42 +/-
      4 micromol/g LDL protein (P = 0.001) on day 60 and dropped to 6 +/- 1 micromol/g
      LDL protein (P = 0.001) on day 120. LDL seemed fully protected with 9.7 +/- 2.5
      micromol beta-carotene/g LDL protein, or 2.3 +/- 1.8 micromol beta-carotene/L
      plasma.

PMID- 9583841
TI  - Use of weighed diet records in the evaluation of diets with different protein
      contents in patients with type 2 diabetes.
AB  - Compliance with diets containing different amounts of protein was studied in 15
      nonobese type 2 diabetes patients (13 males aged 38-69 y). A method based on
      interviews and training in the technique of weighed diet records was used.
      Protein intake recorded by the patients was evaluated on the basis of 24-h
      nitrogen output (criterion standard measurement). Three diets were prescribed in
      random order, each lasting 4 wk: usual diet (UD), chicken diet (CD) (both with
      1.2-1.5 g protein/kg body wt), and low-protein diet (LPD; with 0.5-0.8 g
      protein/kg body wt). Diets were isoenergetic and similar in fat content.
      Nutritional status was not altered during the study according to anthropometric
      indexes (body mass index, triceps skinfold thickness, midupper arm muscle area,
      and waist-to-hip ratio) and laboratory data (serum albumin, hematocrit, and
      lymphocyte values). The correlation of protein intake recorded on the weighed
      diet records with that estimated by nitrogen output was 0.64 for the UD (P =
      0.01), 0.79 for the CD (P < 0.001), and 0.66 for the LPD (P = 0.008). No
      difference was found in mean protein intake (g/kg body wt) calculated from the
      weighed diet records and nitrogen output for the UD (1.37 compared with 1.36 g/kg
      body wt) and CD (1.38 compared with 1.32 g/kg body wt). With the LPD, patients
      did not consume more protein than prescribed, but underreported their actual
      protein intake by 13% (0.68 compared with 0.78 g/kg body wt, P < 0.05) . In
      conclusion, the method of weighed diet records was sufficiently accurate for
      assessing protein intake in this sample of type 2 diabetes patients.

PMID- 9583842
TI  - Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a
      double-blind, randomized, factorial-design, controlled trial.
AB  - Mild hyperhomocysteinemia is accepted as a risk factor for premature
      cardiovascular disease. In a population with a high prevalence of cardiovascular
      disease, we screened a group of clinically healthy working men aged 30-49 y (n =
      509) for plasma homocysteine and 5,10-methylene tetrahydrofolate reductase
      (MTHFR) genotype status. Those with mildly elevated homocysteine concentrations
      (> or = 8.34 micromol/L) were selected for intervention. In a randomized,
      factorial-design, controlled trial we assessed the effects of B-group vitamins
      and antioxidant vitamin supplementation on homocysteine concentrations. The 132
      men were randomly assigned to one of four groups: supplementation with B-group
      vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, and 0.02 mg cyanocobalamin),
      antioxidant vitamins alone (150 mg ascorbic acid, 67 mg RRR-alpha-tocopherol, and
      9 mg beta-carotene), B-group vitamins with antioxidant vitamins, or placebo.
      Intervention was double-blind. A total of 101 men completed the 8-wk
      intervention. When homocysteine concentrations were analyzed by group,
      significant (P < 0.001) decreases (32.0% and 30.0%, respectively) were observed
      in both groups receiving B-group vitamins either with or without antioxidants.
      The effect of B-group vitamins alone over 8 wk was a reduction in homocysteine
      concentrations of 27.9% (95% CI: 22.0%, 33.3%; P < 0.001) whereas antioxidants
      alone produced a nonsignificant increase of 5.1% (95% CI: -2.8%, 13.6%; P =
      0.21). There was no evidence of any interaction between the two groups of
      vitamins. The effect of B-group vitamin supplementation seemed to depend on MTHFR
      genotype. Supplementation with the B-group vitamins with or without antioxidants
      reduced homocysteine in the men with mildly elevated concentrations, and hence
      may be effective in reducing cardiovascular risk.

PMID- 9583843
TI  - Plasma and urinary kinetics of the isoflavones daidzein and genistein after a
      single soy meal in humans.
AB  - The aim of this study was to determine the pharmacokinetics and urinary excretion
      patterns of the soy isoflavones daidzein and genistein in humans. Six healthy men
      with a mean age of 37 y and a mean body mass index (in kg/m2) of 24 consumed a
      soybean flour-based meal on two occasions approximately 6 d apart. Blood samples
      and total urine were collected at intervals for the measurement of daidzein and
      genistein with HPLC. Isoflavone concentrations rose slowly and reached maximum
      values of 3.14 +/- 0.36 micromol/L at 7.42 +/- 0.74 h for daidzein and 4.09 +/-
      0.94 micromol/L at 8.42 +/- 0.69 h for genistein. Elimination half-lives were 4.7
      +/- 1.1 and 5.7 +/- 1.3 h for daidzein and genistein, respectively. The slow
      increase in plasma concentrations is consistent with the facilitation of
      absorption by hydrolysis in the small and large intestines of the glycosidic
      forms of the isoflavones present in soybean-containing foods to their
      corresponding aglycones. The rate of urinary excretion of daidzein was greater
      than that of genistein throughout the postmeal period, with mean recoveries of 62
      +/- 6% and 22 +/- 4% (P < 0.001) for daidzein and genistein, respectively.
      However, the ratio of the areas under the plasma concentration versus time curves
      for genistein and daidzein was equal to the ratio of the concentrations of the
      respective isoflavones in the soy meal. It is concluded that the
      bioavailabilities of daidzein and genistein are similar, not withstanding the
      difference in urinary excretion.

PMID- 9583844
TI  - Influence of ascorbic acid on iron absorption from an iron-fortified, chocolate
      flavored milk drink in Jamaican children.
AB  - The influence of ascorbic acid on iron absorption from an iron-fortified,
      chocolate-flavored milk drink (6.3 mg total Fe per serving) was evaluated with a
      stable-isotope technique in 20 6-7-y-old Jamaican children. Each child received
      two test meals labeled with 5.6 mg 57Fe and 3.0 mg 58Fe as ferrous sulfate on 2
      consecutive days. Three different doses of ascorbic acid (0, 25, and 50 mg per 25
      g serving) were evaluated in two separate studies by using a crossover design.
      Iron isotope ratios were measured by negative thermal ionization mass
      spectrometry. In the first study, iron absorption was significantly greater (P <
      0.0001) after the addition of 25 mg ascorbic acid: geometric mean iron absorption
      was 1.6% (range: 0.9-4.2%) and 5.1% (2.2-17.3%) for the test meals containing 0
      and 25 mg ascorbic acid, respectively. In the second study, a significant
      difference (P < 0.05) in iron absorption was observed when the ascorbic acid
      content was increased from 25 to 50 mg: geometric mean iron absorption was 5.4%
      (range: 2.7-10.8%) compared with 7.7% (range: 4.7-16.5%), respectively. The
      chocolate drink contained relatively high amounts of polyphenolic compounds,
      phytic acid, and calcium, all well-known inhibitors of iron absorption. The low
      iron absorption without added ascorbic acid shows that chocolate milk is a poor
      vehicle for iron fortification unless sufficient amounts of an iron-absorption
      enhancer are added. Regular consumption of iron-fortified chocolate milk drinks
      containing added ascorbic acid could have a positive effect on iron nutrition in
      population groups vulnerable to iron deficiency.

PMID- 9583845
TI  - Effects of age of introduction of complementary foods on iron status of breast
      fed infants in Honduras.
AB  - To evaluate the effect of introducing complementary foods before 6 mo of age, we
      randomly assigned 164 infants who had been exclusively breast-fed for 4 mo to
      continue being exclusively breast-fed until 6 mo (EBF group) or to receive iron
      fortified foods in addition to breast milk from 4 to 6 mo (BF+SF group). At 6 mo,
      the BF+SF group had higher mean iron intake (4 mg/d compared with 0.2 mg/d in EBF
      infants) and higher hemoglobin, hematocrit, and ferritin values than the EBF
      group (P < 0.05). The percentage with low hemoglobin (< 103 g/L) did not differ
      significantly between groups, but fewer infants in the BF+SF group had a low
      hematocrit (< 0.33; 21.4% compared with 32.0%, respectively; P < 0.05). The
      percentage of infants with ferritin concentrations < 12 microg/L at 6 mo was
      lower than the percentage with low hemoglobin or hematocrit, raising questions
      about the validity of the cutoffs at this age. Infants at greatest risk for
      anemia and low ferritin were those with birth weights < 2500 g; no infant with a
      birth weight > 3000 g had a low ferritin value at 6 mo. We conclude that the risk
      of iron deficiency is low among infants with birth weights > 3000 g who are
      exclusively breast-fed for 6 mo. Iron drops are recommended for low-birth-weight
      infants; for breast-fed infants with birth weights between 2500 and 3000 g,
      further research is needed to determine whether iron drops are more effective
      than complementary foods for preventing iron deficiency before 6 mo.

PMID- 9583846
TI  - Energy utilization and growth in breast-fed and formula-fed infants measured
      prospectively during the first year of life.
AB  - This study is the first to report approximations of energy requirements for male
      and female breast-fed and formula-fed infants based on individual estimates of
      total daily energy expenditure (TDEE) and energy deposition derived from total
      body fat (TBF) and fat-free mass (FFM) gain as determined by total-body
      electrical conductivity. In 46 healthy, full-term infants the effect of > or = 4
      mo of exclusive breast-feeding compared with formula feeding on macronutrient and
      energy intake, TDEE, energy deposition, and growth were investigated
      prospectively. Metabolizable energy intake (MEI) was assessed from macronutrient
      intake by test weighing (MEI-TW) and from the sum of TDEE and energy deposition
      (MEI-Pred). At 1-2, 2-4, 4-8, and 8-12 mo of age MEI-Pred averaged 431 +/- 38,
      393 +/- 33, 372 +/- 33, and 355 +/- 21 kJ x kg(-1) x d(-1) for boys, and 401 +/-
      59, 376 +/- 25, 334 +/- 33, and 326 +/- 17 kJ x kg(-1) x d(-1) for girls. No
      significant difference between breast-fed and formula-fed infants was found with
      respect to weight, length, head circumference, TBF, FFM, and TDEE at all ages, or
      for gain in length, weight, TBF, and FFM. MEI-TW was significantly different
      between feeding groups at 1-4 mo of age (formula-fed being greater than breast
      fed, P < 0.005). This feeding effect, however, was not significant for MEI-Pred
      (MJ/d). MEI-TW differed from MEI-Pred only in breast-fed infants at 1-4 mo (P <
      0.05 at 2-4 mo). The data from this study indicate that energy requirements in
      infants are lower than the recommendations in guidelines currently in use.

PMID- 9583847
TI  - Postpartum maternal blood helper T (CD3+CD4+) and cytotoxic T (CD3+CD8+) cells:
      correlations with iron status, parity, supplement use, and lactation status.
AB  - Iron deficiency reduces T cell counts; however, iron sufficiency is difficult to
      maintain during pregnancy and to reestablish in the early postpartum period. This
      cross-sectional study examined relations among postpartum maternal iron status,
      parity, lactation, supplement use, and maternal blood T cell populations. Sixty
      lactating and 41 nonlactating postpartum (NLPP) women at 1-2 wk and 1, 2, 4, or 8
      mo postpartum and 13 nulliparous women were studied. Among multiparous women,
      multiple linear regression showed that relative percentages and absolute numbers
      of CD3+CD8+ cells were correlated positively with maternal serum transferrin
      saturation. In a separate multiple linear regression model, multiparous NLPP
      women who did not use multivitamin and mineral supplements had lower CD3+CD4+
      cell percentages in the first month postpartum than did nulliparous control
      women. Lactating women who used supplements, however, had reduced CD3+CD4+
      percentages 4-8 mo postpartum compared with control women. CD3+CD4+ percentages
      did not differ among control women, NLPP women who used supplements, or lactating
      women who did not use them. These results suggest that nutritional factors such
      as maternal iron status and use of dietary supplements play a role in a mother's
      postpartum immune status.

PMID- 9583848
TI  - Total energy expenditure and physical activity as assessed by the doubly labeled
      water method in Swedish adolescents in whom energy intake was underestimated by 7
      d diet records.
AB  - Swedish children and adolescents may be adopting a sedentary lifestyle with low
      energy expenditures and intakes, but no quantitative data are available. The
      purpose of the present study in 50 adolescents aged 15 y was to investigate
      whether assessment of total energy expenditure (TEE) and physical activity level
      (PAL) by the doubly labeled water method and indirect calorimetry and estimation
      of energy intake by a 7-d diet record would indicate physical inactivity. The
      boys' (n = 25) mean weight was 112% and the girls' (n = 25) was 109% of Swedish
      reference values from 1976; the mean height of both boys and girls was 102% of
      those reference values. Mean TEE in the boys and girls, 13.82 +/- 1.90 and 10.70
      +/- 1.59 MJ/d, and mean PAL (TEE/basal metabolic rate), 1.89 +/- 0.16 and 1.79 +/
      0.22, respectively, were nonsignificantly higher than corresponding figures from
      other published studies. Mean energy intake as a percentage of TEE was 81.9 +/-
      17.9% in the boys and 78.3 +/- 16.4% in the girls. Significant negative
      correlations were found both between energy intake as a percentage of TEE and
      percentage body fat and between energy intake as a percentage of TEE and body
      mass index. These results add to the evidence that 7-d diet records underestimate
      energy intake in adolescents, particularly those with a tendency for overweight
      and increased body fat. The results support indications of a trend of increasing
      body weight and height in Swedish adolescents, but conflict with the presumptions
      of low physical activity, low energy expenditure, and low energy intake. These
      results support the view that current recommendations for energy intake during
      adolescence are too low.

PMID- 9583849
TI  - Biochemical assessment of the nutritional status of cystic fibrosis patients
      treated with pancreatic enzyme extracts.
AB  - We examined the protein and fat nutritional status of 65 cystic fibrosis patients
      aged 4-26 y (x +/- SD: 11.2 +/- 5.6 y). Patients were treated with pancreatic
      enzyme extracts to improve nutrient absorption; in addition, most patients were
      supplemented with vitamins A and E. Results were compared with those in a control
      group of 39 subjects aged 5-29 y (x: 14.3 +/- 5.6 y) with no digestive diseases
      or nutritional deficiencies. Protein determination showed low albumin
      concentrations in 42% of the cystic fibrosis patients and decreased blood
      concentrations of retinol binding protein in 12% of the patients. Lipoprotein
      components were characterized by decreased cholesterol concentrations in 25% of
      the cystic fibrosis group. Also, mean concentrations of apolipoprotein A-I were
      significantly lower in the cystic fibrosis group than in control subjects. The
      results of fatty acid status, expressed in relative (%) and absolute (mg/L)
      values, showed concentrations of essential fatty acids, represented by linoleic
      and arachidonic acids, to be significantly decreased in cystic fibrosis patients;
      this decrease was markedly significant for fatty acid status expressed in
      absolute values, especially in the cholesteryl ester subfraction. Serum retinol
      and alpha-tocopherol concentrations were lowered by 8% and 46% in cystic fibrosis
      patients and control subjects, respectively: retinol, 1.80 +/- 0.50 and 2.37 +/-
      0.60 micromol/L, P < 0.001, and alpha-tocopherol, 18.1 +/- 8.7 and 25.7 +/- 5.0
      micromol/L, P < 0.001. In conclusion, despite regular treatment with pancreatic
      enzyme replacements, neither protein nor fat malnutrition in cystic fibrosis
      patients was completely corrected.

PMID- 9583850
TI  - Comprehensive nutritional status in patients with long-standing Crohn disease
      currently in remission.
AB  - Malnutrition is observed frequently and is an important complication in patients
      with Crohn disease (CD). The pathophysiology of malnutrition in this disorder is
      complex. To obtain a comprehensive picture of nutritional status in patients with
      long-standing CD that was clinically in remission, we assessed four measures of
      nutritional status in 32 patients (18 women and 14 men) and 32 matched healthy
      control subjects: 1) body composition, 2) dietary intake, 3) biochemical indexes
      of nutrition, and 4) and muscle strength (as a functional index). Mean daily
      intakes of fiber and phosphorus were significantly lower in CD patients than in
      control subjects. Serum concentrations of several nutrients (beta-carotene,
      vitamin C, vitamin E, selenium, and zinc) and activity of the enzyme glutathione
      peroxidase were also significantly lower in CD patients, as were antioxidant
      status and serum concentrations of magnesium and vitamin D. Percentage body fat
      and hamstring muscle strength were significantly lower in male CD patients than
      in control subjects, whereas muscle strength of the quadriceps was preserved. In
      conclusion, this study showed a variety of nutritional and functional
      deficiencies in patients with long-standing CD in remission, especially in male
      patients with a high lifetime prednisone dose. A comprehensive nutritional
      assessment seems superior to the assessment of a single dimension of nutritional
      status.

PMID- 9583851
TI  - Intravenous lipid dose and incidence of bacteremia and fungemia in patients
      undergoing bone marrow transplantation.
AB  - Experimental data have implicated intravenous lipids as being immunosuppressive,
      yet evidence that lipids are associated with an increase in clinically documented
      infections is sparse. A prospective trial conducted in patients with hematologic
      malignancies who were undergoing bone marrow transplantation compared the
      incidence of bacteremia and fungemia during the first month after the transplant.
      Patients (n = 512) were randomly assigned to receive 6-8% (low dose) or 25-30%
      (standard dose) of total daily energy as a 20% lipid emulsion. An adaptive
      randomization scheme stratified for treatments that might influence infection
      outcome (hematopoietic growth factors, fluconazole, graft-versus-host disease
      prophylaxis with steroids, pentoxifylline, intravenous immunoglobulin, and total
      body irradiation). The transplant type (autologous, related family donor, or
      unrelated donor) did not differ in distribution between treatment groups. Of the
      evaluable patients (n = 482), 55 patients in the standard-dose lipid group
      developed bacteremia or fungemia compared with 54 in the low-dose lipid group.
      The log-rank test comparing the time to first infection found no association
      between the incidence of bacteremia or fungemia and intravenous lipid (P = 0.95).
      Similar results were found when analyzed as intent-to-treat (P = 0.98), when
      bacterial or fungal infections at all sites were included (P = 0.94), and when
      the observation period was extended to 60 d (P = 0.58 for blood infections, P =
      0.77 for infections at all sites). These data indicate that moderate amounts of
      intravenous lipid rich in linoleic acid are not associated with an increased
      incidence of bacterial or fungal infections in patients undergoing bone marrow
      transplantation and receiving total parenteral nutrition.

PMID- 9583852
TI  - Improving power with repeated measures: diet and serum lipids.
AB  - The inability to detect associations between diet and serum cholesterol in cross
      sectional population studies has been attributed to measurement error in diet
      assessments and between-subject variability in lipid concentrations. Current
      statistical methods can reduce the effects of measurement error and allow within
      subject comparisons when replicate measures on individuals are available, even if
      the time between replicates is as long as 4 y and replicate data are not
      available for all subjects. Data from 928 nondiabetic participants of the San
      Luis Valley Diabetes Study with measures of 24-h dietary intake and fasting lipid
      concentrations at baseline, at a 4-y follow-up visit, or both were analyzed in a
      random-effects model that allowed for an unbalanced design. Sex was included as a
      non-time-varying covariate and age, body mass index, and energy intake were
      included as time-varying covariates. The findings when LDL cholesterol (mmol/L)
      was regressed on saturated fat intake (20 g/d) with all observations in a random
      effects model (beta = 0.14, P = 0.0016) were compared with results with
      observations restricted to the first visit only (beta = 0.05, P = 0.52), a
      balanced design using averages across visits (beta = -0.12, P = 0.28), and a
      balanced design with random effects obtained by excluding subjects without two
      observations (beta = 0.12, P = 0.0092). Study power was greatest in the random
      effects model using all observations and time-varying covariates. These findings
      highlight the importance of even a single replicate observation on a subsample of
      subjects. We recommend analyzing all data rather than averaging measures across
      visits or omitting observations to create a balanced design.

PMID- 9583853
TI  - Growth, morbidity, and mortality of children in Dhaka after treatment for severe
      malnutrition: a prospective study.
AB  - Over 1300 severely malnourished children (< 60% of US National Center for Health
      Statistics weight-for-height, with edema, or both) are admitted each year to the
      Children's Nutrition Unit in Dhaka. Fatality during treatment is low and recovery
      is rapid. Our aim was to determine whether this initial success is sustained when
      children return home. A previous attempt to address this question was frustrated
      by the difficulty in tracing children after discharge because most are from slum
      settlements and families move frequently. This prospective study with fortnightly
      monitoring was therefore undertaken. The main outcomes of interest were
      anthropometric status, relapse, morbidity, and mortality. Children (n = 437) who
      had been treated for severe malnutrition when aged 12-59 mo and had reached the
      discharge criterion of 80% of weight-for-height, were followed for the next 12
      mo. During follow-up, 7.5% were lost without trace, 0.6% relapsed, and 2.3% died.
      Morbidity was high, with a mean of seven episodes of diarrhea during the year.
      Outpatient visits for diarrhea occurred for 67% of children, and 58% had
      pneumonia (10% had pneumonia three times). After 12 mo, mean weight-for-height
      was 91% (-0.92 z score) but mean height-for-age remained at 84% (-4.14 z score).
      Weight gain, but not height gain, tended to be lower in children who experienced
      more diarrhea. Fever and cough were not associated with either weight or height
      gain. The high prevalence of illness highlights the need for continued accessible
      health care and for interventions to reduce disease acquisition.

PMID- 9583854
TI  - Long-term maintenance of weight loss.

PMID- 9583855
TI  - Dairy product-rich diets and cytotoxicity of fecal water.

PMID- 9583856
TI  - Nutrition, immunity, and refeeding.

PMID- 9583857
TI  - Zinc balance in adolescent females.

PMID- 9583858
TI  - Gentle in situ liver manipulation during organ harvest decreases survival after
      rat liver transplantation: role of Kupffer cells.
AB  - BACKGROUND: The etiology of primary graft nonfunction and dysfunction is unknown
      but most likely involves Kupffer cell-dependent reperfusion injury. However, the
      donor operation and surgical technique may also have an effect on the outcome
      after transplantation. Because liver manipulation during harvest cannot be
      prevented completely with standard procedures, its effect on survival was
      assessed here. METHODS: Donor livers were harvested from female Sprague-Dawley
      rats (200-230 g). Briefly, after minimal dissection during the first 12 min,
      livers were either manipulated gently or left alone for 13 subsequent minutes. At
      25 min, all livers were perfused with cold University of Wisconsin solution via
      the portal vein, and transplantation was performed after cold storage (1 hr). In
      some rats, Kupffer cells were destroyed with gadolinium chloride or inactivated
      with dietary glycine before harvest. Survival, proteolytic activity in the rinse
      effluent, serum transaminases, trypan blue distribution to index
      microcirculation, and histology were compared. RESULTS: In the nonmanipulated
      group, survival was 100% after transplantation; however, gentle manipulation
      decreased survival by 70%. Further, manipulation elevated transaminases fivefold
      and caused about 200% necrosis. At harvest, proteolytic activity and the time for
      trypan blue to distribute homogeneously were elevated three- to eightfold by
      manipulation. Gadolinium chloride and glycine prevented the effects of
      manipulation on all parameters studied. CONCLUSION: These data indicate for the
      first time that brief, gentle manipulation of the donor liver has a marked
      detrimental effect on survival by priming or activating Kupffer cells. This may
      represent an important early event in pathogenesis, because Kupffer cells play an
      important role in primary graft nonfunction.

PMID- 9583859
TI  - Effectiveness of ischemic preconditioning on long-term myocardial preservation.
AB  - BACKGROUND: This study was designed to assess whether the protective effect of
      ischemic preconditioning can be adapted for myocardium undergoing 6 hr of
      ischemia. METHODS: Eighteen isolated rat hearts were perfused with oxygen
      bicarbonated Krebs-Henseleit buffer in the Langendorff mode for 35 min (group A,
      controls) or perfused in the Langendorff apparatus for 20 min, followed by 5 min
      of global normothermic ischemia and 10 min of buffer perfusion (group B,
      preconditioning) or followed by two cycles of 2.5 min of global normothermic
      ischemia plus 5 min of buffer perfusion (group C, preconditioning). The hearts
      were then arrested and preserved for 6 hr with Bretschneider's histidine
      tryptophan-potassium cardioplegic solution at 4 degrees C, followed by 30 min of
      reperfusion. Recovery of cardiac function, postischemic enzyme leakage, and
      intracellular calcium concentration were compared. RESULTS: After 6 hr of
      ischemia, the hearts that underwent preconditioning in groups B and C showed
      better recovery of left ventricular developed pressure (P<0.05), a lower end
      diastolic pressure level (P<0.05), less leakage of creatine kinase, and a lower
      intracellular calcium concentration than those in group A. There were no
      statistical differences in the rate of recovery of coronary flow. CONCLUSIONS:
      Our study demonstrated that ischemic preconditioning improves myocardial
      functional recovery after 6 hr of hypothermic preservation in the isolated rat
      heart. Preconditioning might be useful for preserving the heart against long-term
      ischemia/reperfusion injury.

PMID- 9583860
TI  - Exposure of vascular allografts to insulin-like growth factor-I (IGF-I) increases
      vascular expression of IGF-I ligand and receptor protein and accelerates
      arteriosclerosis in rats.
AB  - BACKGROUND: Accelerated arteriosclerosis limits the survival of transplanted
      hearts. We hypothesized that insulin-like growth factor-I (IGF-I) is crucial in
      accelerating transplant arteriosclerosis. Recently, we reported that exposure to
      IGF-I prior to transplantation accelerates transplant arteriosclerosis in the rat
      aorta allograft model. Here, we studied the mechanism whereby IGF-I exposure
      accelerates transplant arteriosclerosis. METHODS: The abdominal aorta was
      harvested from male Brown Norway rats and exposed to 0, 200, or 500 ng/ml of IGF
      I at 37 degrees C for 30 min prior to transplantation to the abdominal position
      of male Lewis rats. The allografts were harvested 14 days later and processed for
      immunohistochemical staining for alpha-actin, growth factors (IGF-I, IGF-I
      receptor, platelet-derived growth factor-BB, and basic fibroblast growth factor),
      and immunological markers (major histocompatibility complex class II antigen,
      macrophage, and CD4- and CD8-positive T cells). RESULTS: By 14 days, the ex vivo
      IGF-I donor aorta treatment with IGF-I increased in a concentration-dependent
      manner the expression of IGF-I and IGF-I receptor in both the intima and the
      adventitia. In contrast, the expression of platelet-derived growth factor-BB was
      decreased in a concentration-dependent manner in the intima while basic
      fibroblast growth factor remained unchanged. The cell-mediated immune response
      was not affected by IGF-I at 14 days after transplantation, which suggests that
      the immune events associated with acceleration of transplant arteriosclerosis may
      occur at an earlier time. CONCLUSION: Acceleration of transplant arteriosclerosis
      by exposure to IGF-I is associated with increased IGF-I ligand and receptor
      expression in the allograft vascular wall. These data further suggest that IGF-I
      may be a major factor in mediating graft arteriosclerosis.

PMID- 9583861
TI  - Effect of different immunosuppressive agents on acute pancreatitis: a comparative
      study in an improved animal model.
AB  - BACKGROUND: Immunosuppressive drugs have been associated with the development and
      progression of acute pancreatitis after organ transplantation. Consequently, a
      reduction or a change in immunosuppressive therapy has been recommended once
      posttransplantation pancreatitis has been suspected. However, it is not known
      which of the available immunosuppressive agents is most harmful to the pancreas
      and which may be used safely in this situation. The objective of this study was
      to investigate the effect of different immunosuppressive drugs in various dosages
      on intrapancreatic protease activation, acinar cell necrosis, and mortality in an
      improved model of acute necrotizing pancreatitis in the rat. The rat model of
      acute necrotizing pancreatitis, like posttransplantation pancreatitis, is
      characterized by ischemia and microcirculatory disorders. METHOD: Acute
      pancreatitis was induced in rats by using a combination of low-dose controlled
      intraductal glycodeoxycholic acid superimposed on intravenous cerulein
      hyperstimulation. Six hours thereafter, animals were randomized to intravenous
      therapy with 2, 10, or 50 mg/kg/day prednisolone (PRED); 3, 15, or 60 mg/kg/day
      cyclosporine A (CsA); 10 mg/kg/day azathioprine (AZA); 0.6 mg/kg/day orthoclone
      OKT3 (OKT3); or saline. After 36 hr, surviving animals were killed to determine
      acinar cell necrosis and trypsinogen activation peptides levels (TAP) in blood
      and ascites. RESULTS: Compared with saline-treated control rats, animals treated
      with 60 mg/kg/day CsA developed significantly more acinar cell necrosis and had
      increased amounts of TAP in ascites. Likewise, there was more extensive acinar
      cell necrosis in animals subjected to AZA therapy. However, this was not
      associated with incremental TAP. Animals treated with 3 or 15 mg/kg/day CsA,
      OKT3, or PRED showed no significant changes in these target parameters. Animals
      given 10 or 50 mg/kg/day PRED even had decreased hematocrit values and produced
      significantly less ascites than animals in the other groups. CONCLUSION: The
      present results suggest that AZA and high doses of CsA aggravate acute
      pancreatitis and should, therefore, be avoided once posttransplantation
      pancreatitis has been suspected, whereas lower doses of CsA, OKT3, and PRED may
      be used safely. PRED can even be used at higher doses as may be required when
      graft rejection is suspected.

PMID- 9583862
TI  - Indefinite survival of skin allografts in adult thymectomized, antilymphocyte
      serum-treated mice given bone marrow and thymus grafts of donor origin: tolerance
      induction by donor bone marrow and thymus.
AB  - BACKGROUND: Perigraft immunosuppression with antilymphocyte serum (ALS) and
      postgraft infusion of donor bone marrow cells (BMC), which induces allograft
      unresponsiveness in a class I major histocompatibility complex (MHC)-disparate
      mouse combination, is much less effective in class I and II MHC-disparate strain
      combinations. Because the thymus plays a central role in the maturation,
      differentiation, and education of T lymphocytes, which are the principal mediator
      of allograft responses, we examined whether transplantation of donor-specific
      thymus combined with adult thymectomy of recipients enhances the tolerogenic
      effect of ALS and donor BMC infusion in a strongly histoincompatible class I and
      II MHC-disparate DBA/2-to-B6AF1 mouse strain combination. METHODS: Adult
      thymectomy was performed 4 weeks before grafting. B6AF1 mice received ALS (days 
      1 and 2), skin allografts (day 0), and BMC and/or thymus grafts (ThyTx) (day 7).
      Flow cytometric analysis was used to detect donor cells in tolerant mice.
      Limiting dilution assay was used to calculate the frequencies of precursor
      cytotoxic T lymphocytes against donor and third-party alloantigens. The presence
      of suppressor cells was determined by in vivo adoptive transfer assay and in
      vitro coculture mixed lymphocyte culture. RESULTS: When adult thymectomy and
      postgraft donor ThyTx were combined with ALS and donor BMC, DBA/2 allograft
      survival was prolonged with all grafts surviving for >122 days. Third-party
      (DBA/1) or recipient ThyTx was not effective. The tolerant mice accepted the
      second donor skin allografts but acutely rejected the third-party grafts. No
      significant chimerism was detected. Marked reduction of precursor cytotoxic T
      lymphocyte frequencies continued only against donor alloantigens after second
      donor and third-party skin grafting. No suppressor cell activity was detected.
      Immunopathological analysis revealed that the cells in the ThyTx of tolerant mice
      are of donor origin. CONCLUSION: Donor ThyTx combined with donor BMC infusion in
      adult thymectomized, ALS-treated mice induced clonal deletion of donor-reactive T
      cells.

PMID- 9583864
TI  - Effect of partial HLA class I match on acute rejection in viral pre-infected
      human liver allograft recipients.
AB  - BACKGROUND: Acute rejection in liver transplants is one of the commonest causes
      of liver dysfunction in the early postoperative period. However, the factors
      involved in liver graft rejection are still unknown. Our study was aimed at
      ascertaining whether the degree of HLA class I and class II compatibility or
      pretransplant viral infection have any influence on early acute liver graft
      rejection. METHODS: We reviewed clinical and laboratory data in 190 consecutive
      patients who underwent a liver transplant. HLA-A, HLA-B, and HLA-DR typing for
      the establishment of an HLA match score was performed by a standard
      microcytotoxicity method. The existence of pretransplant viral infection was
      investigated in sera and biopsy tissue by serologic (hepatitis B virus, hepatitis
      C virus) and polymerase chain reaction (cytomegalovirus) techniques,
      respectively. The influence of these two factors in acute rejection and the
      interaction between them was also analyzed. RESULTS: A strong association between
      viral infection and acute rejection in the group with partial class I matching
      was found (odds ratio=7.75; P<0.0009), whereas no correlation was observed in the
      group with zero class I matching (odds ratio=0.98; P=0.81). The rejection
      percentage in the group in which partial class I match and viral infections
      coexisted was 60%, whereas in the partially class I-matched group without
      pretransplant viral presence it was 16%. CONCLUSIONS: These findings suggest a
      participation of partial HLA class I compatibility in triggering acute rejection
      in recipients suffering preoperative viral infections and support the idea that
      HLA class I antigen matching could play a role as a linking element between the
      MHC-restricted T cell-mediated response to viral infection and the allogenic
      response in liver transplantation.

PMID- 9583863
TI  - Comparison of tacrolimus with microemulsion cyclosporine as primary
      immunosuppression in hepatitis C patients after liver transplantation.
AB  - BACKGROUND: Immunosuppression in patients with hepatitis C virus (HCV) following
      orthotopic liver transplantation can lead to significant increases in serum viral
      loads. Our aim was to analyze the effect of a randomized study of two
      immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the
      outcome of HCV patients following orthotopic liver transplantation. METHODS: From
      December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis
      were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or
      microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received
      alpha-interferon after transplantation, and the overall steroid doses were no
      different between the groups. Serum RNA levels were measured by signal
      amplification of Chiron. Biopsies were taken when transaminases were greater than
      2x base line or when there was an inappropriate response to alterations in
      immunosuppression regimens. RESULTS: There were more episodes of rejection in the
      Neoral group, but there were no differences in bacterial and viral infections,
      nor in the rate of HCV recurrence between the two groups. There were seven deaths
      in group 1 and eight in group 2. Overall patient and graft survival rates in the
      Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%,
      respectively. CONCLUSIONS: (a) Both immunosuppression regimens had similar HCV
      recurrence rates; (b) there were no differences in bacterial or opportunistic
      infections; and (c) patient and graft survival was similar between the two
      groups.

PMID- 9583865
TI  - Single-center long-term results of renal transplantation for IgA nephropathy.
AB  - BACKGROUND: Previous reports with short-term follow-up after renal
      transplantation for IgA nephropathy (IgAN) have suggested an incidence of
      recurrence up to 50%, an increased recurrence with living-related donors, and the
      rarity of graft loss due to recurrence. In this study, the long-term results of
      renal transplantation for IgAN were examined. METHODS: Between June 1980 and
      December 1994, 54 patients (61 renal transplants) with end-stage renal disease
      due to IgA nephropathy were performed at the University of California San
      Francisco. Actuarial patient and graft survival were compared with a matched
      reference group. Correlates of recurrent disease (biopsy confirmed) and graft
      loss were determined. RESULTS: Patient and graft survival for IgA patients were
      good (100% and 75%, respectively, at 5 years after transplant). Graft survival
      was lower in IgA recipients with living-related compared with cadaveric renal
      allografts (P<0.09) and also with renal allografts well matched at HLA-AB (< or
      =2 AB mismatches) (P<0.09) or HLA-DR (< or =1 mismatch) (P<0.01). Recurrence was
      not correlated with donor status, recipient age, race, gender, or
      immunosuppression. Recurrence (18 of 61) resulted in substantial graft loss (6 of
      18) or deteriorating renal function (4 of 18) at a mean follow-up of 61 months.
      Mean time to diagnosis of recurrence and subsequent graft loss was 31 and 63
      months, respectively. Despite re-recurrence of IgAN in three of five patients who
      were retransplanted, all have good long-term renal function. CONCLUSIONS:
      Substantial graft loss due to recurrent disease after renal transplantation for
      IgAN occurs with long-term follow-up. Living-related transplantation and HLA
      matching do not appear to confer an advantage for graft survival in patients with
      IgAN. Despite the potential for recurrence, IgAN patients enjoy good long-term
      graft survival.

PMID- 9583866
TI  - A comparison of media supplement methods for the extended culture of human islet
      tissue.
AB  - BACKGROUND: The preservation of sufficient quantities of islets for human
      transplantation has proven to be a tenacious problem for researchers and
      transplant programs. Beyond the variables associated with islet procurement,
      there is the problem of tissue storage before transplantation. Cryopreservation
      has been adopted as a method for long-term islet storage that allows for recovery
      of viable tissue. However, there is significant tissue loss during the process
      and the possibility that long-term viability may be compromised. An alternate
      method of prolonged culture at 24 degrees C was initially introduced as a means
      of reducing islet antigenicity. Although successful in the short term, prolonged
      culture with serum-based media has also resulted in a significant loss of tissue.
      In this study, we report the successful use of an ITS+ Premix-supplemented serum
      free media for prolonged islet culture and its comparison to fetal bovine serum
      supplemented media and to cryopreservation. METHODS: Pancreata were procured from
      cadaveric organ donors, and islets were isolated using our own modification of
      the automated method of Ricordi. Aliquots from a series of human islet isolations
      were cultured in parallel in (A) CMRL + ITS (serum-free media; SFM) or (B) CMRL
      +10% fetal bovine serum (standard media) and compared with cryopreserved and
      thawed tissue. RESULTS: Our results show that SFM allows for the long-term
      culture of islet tissue. For time points up to 2 months, islets cultured in SFM
      showed recovery ratios greater than those for standard serum-supple. mented
      media. At 1 week and 1 month, islet recovery ratios were greater for SFM-cultured
      islets than for cryopreserved tissue. Viability studies confirmed that the SFM
      cultured islets were able to respond to glucose stimulation (stimulation index
      0.8-21.2). Additionally, in vivo results using cultured islets in a patient
      demonstrated good islet function, with a 1-month stimulation index of 4.02 in
      response to an intravenous glucose tolerance test. CONCLUSION: We conclude that
      this culture modification represents a method by which functional islet tissue
      can be maintained in long-term culture and successfully transplanted.

PMID- 9583868
TI  - High incidence of antitissue antibodies in patients experiencing chronic liver
      allograft rejection.
AB  - BACKGROUND: The precise immunologic mechanisms responsible for chronic rejection
      of liver allografts are unknown. We have recently shown in a rodent model that
      recipients of liver allografts developed non-major histocompatibility complex
      antitissue antibodies. The aim of the present study was to test this hypothesis
      in the clinical setting. METHODS: Posttransplant sera of 14 patients undergoing
      chronic rejection and of 48 control patients (12 liver transplant patients with
      chronic active hepatitis or liver cirrhosis related to hepatitis C virus [HCV]
      infection and without chronic rejection, 10 with sclerosing cholangitis, and 26
      with normal liver function tests and liver biopsy) were tested for the presence
      of antitissue antibodies by indirect immunofluorescence. Pretransplant sera of
      all these patients lacked antitissue antibodies. RESULTS: Antitissue antibodies
      were detected in 71% of patients who developed chronic rejection (before or at
      the time of chronic rejection). This incidence was significantly greater than
      that observed in patients not undergoing rejection (HCV-related chronic active
      hepatitis, 16%; sclerosing cholangitis, 0%; normal liver biopsy, 7%). All these
      autoantibodies were directed against the smooth muscle and/or the nucleus. In two
      patients, anti-smooth muscle antibodies had an antiactin or antivimentin
      specificity. CONCLUSIONS: These results show a strong association between chronic
      allograft rejection and the development of antitissue antibodies and suggest that
      these antibodies could be used to identify patients at high risk of developing
      chronic rejection after liver transplantation.

PMID- 9583867
TI  - Quantitation of immunosuppression by flow cytometric measurement of the capacity
      of T cells for interleukin-2 production.
AB  - BACKGROUND: Methods to quantitate the effects of immunosuppressive drugs on
      immune reactivity might be helpful for monitoring immunosuppressive treatment.
      Cyclosporine (CsA) inhibits the induction of cytokine synthesis in T cells, and
      measurement of interleukin (IL)-2 production might constitute a parameter of this
      drug's effect. METHODS: We determined the percentages of CD4+ and CD8+
      lymphocytes producing IL-2 upon stimulation by phorbol myristate acetate and
      calcium ionophore in whole blood culture, using immunostaining of
      intracytoplasmatic and membrane markers, followed by multiparameter flow
      cytometry. A total of 38 clinically stable transplant patients on various
      immunosuppressive protocols were studied. RESULTS: The percentage of CD4+ T cells
      producing IL-2 was strongly reduced in patients compared with healthy controls
      (23% [range, 3-68%] vs. 59.0% [range, 41-70%]; P=0.000035). The percentage of
      CD4+ T cells producing IL-2 was negatively correlated with the CsA level (Rc=
      0.0821, P=0.00002297) but not with prednisolone or azathioprine doses. Fewer CD8+
      T cells produced IL-2 in transplant patients compared with controls, but the
      difference failed to reach statistical significance. The percentage of CD8+ T
      cells capable of producing IL-2 was inversely correlated to CsA levels (Rc=
      0.0375, P=0.0011). CONCLUSIONS: These data suggest that the functional effects of
      CsA in transplant recipients can be quantitatively determined and that the
      capacity of CD4+ T cells to produce IL-2 upon stimulation constitutes a
      functional parameter of CsA effects on the immune system. Prospective studies are
      required to determine whether this method is useful for clinical monitoring.

PMID- 9583869
TI  - Enhancing the effect of secreted cyclophilin B on immunosuppressive activity of
      cyclosporine.
AB  - BACKGROUND: Cyclophilin B (CyPB) is a cyclosporine (CsA)-binding protein, located
      within intracellular vesicles and secreted in biological fluids. In previous
      works, we reported that CyPB specifically interacts with the T-cell membrane and
      potentiates the ability of CsA to inhibit CD3-induced proliferation of T
      lymphocytes. METHODS: CyPB levels were measured in plasma from healthy donors and
      transplant patients. The role of extracellular CyPB on the distribution and
      activity of CsA was investigated first by studies on the uptake of free and CyPB
      complexed drug by blood cells, and second by studies on the inhibitory effects of
      these two compounds on the CD3-induced proliferation of peripheral blood
      mononuclear cells. RESULTS: A significant increase in plasma CyPB level was
      observed for CsA-treated patients (13+/-6.4 nM, n=42) in comparison with
      untreated donors (4.3+/-2.1 nM, n=34). In vitro, extracellular CyPB dose
      dependently modified CsA distribution between plasma, erythrocyte, and lymphocyte
      contents, by both retaining the complexed drug extracellularly and promoting its
      specific accumulation within peripheral blood mononuclear cells. Moreover, the
      enhanced ability of CyPB-complexed CsA to suppress CD3-induced T-cell
      proliferation was preserved in the presence of other blood cells, implying
      specific targeting of the drug to sensitive cells. Furthermore, although a large
      interindividual variability of sensitivity to the drug was confirmed for 18
      individuals, we found that CyPB potentiated the activity of CsA in restoring a
      high sensitivity to the immunosuppressant. CONCLUSION: These results suggest that
      plasma CyPB may contribute to the acceptance and the good maintenance of organ
      transplantation by enhancing the immunosuppressive activity of CsA through a
      receptor-mediated incorporation of CyPB-complexed CsA within peripheral blood
      lymphocytes.

PMID- 9583870
TI  - Complement-mediated pulmonary xenograft injury: studies in swine-to-primate
      orthotopic single lung transplant models.
AB  - BACKGROUND: The pathogenesis of acute pulmonary xenograft injury has not yet been
      determined. The present study evaluates the role of complement in mediating
      pulmonary xenograft dysfunction by using cobra venom factor (CVF) to deplete
      recipient complement and transgenic swine, which express human regulators of
      complement activation (human decay-accelerating factor [hDAF] and hCD59).
      METHODS: Fifteen orthotopic lung transplants were performed as follows: group I,
      swine-to-swine (n=5); group II, unmodified swine-to-baboon (n=3); group III,
      unmodified swine-to-(CVF treated) baboon (n=3); and group IV, hCD59/hDAF swine-to
      baboon (n=4). Left pulmonary artery flow and pulmonary vascular resistance were
      measured at 30-min intervals. Serial lung biopsies were examined by light
      microscopy and immunofluorescence. The activation of complement was quantified by
      measurement of baboon plasma CH50 and C4 functional activity. RESULTS: Group II
      xenotransplants ceased functioning within 30 min of reperfusion. Histopathologic
      ab normalities included erythrocyte/platelet aggregates and hemorrhagic pulmonary
      edema. Groups I and IV showed excellent function throughout. hDAF/hCD59 lungs
      (group IV) showed trace venular fibrin plugs and moderate loss of alveolar
      architecture. Pretreatment with CVF (group III) was ineffective in preventing
      xenograft injury. CONCLUSIONS: These results characterize the fundamental
      features of discordant pulmonary xenotransplantation. Correction of the known
      defects in the regulation of heterologous complement activation was partially
      effective in preventing pulmonary xenograft dysfunction, suggesting that
      complement mediates, in part, some of the features of acute lung injury after
      discordant lung xenotransplantation.

PMID- 9583871
TI  - Direct antigen presentation through binding of donor intercellular adhesion
      molecule-1 to recipient lymphocyte function-associated antigen-1 molecules in
      xenograft rejection.
AB  - Cellular interactions that lead to graft rejection were examined in a rat-to
      mouse xenogeneic combination using species-specific monoclonal antibodies (mAbs)
      against donor and recipient intercellular adhesion molecule-1 (ICAM-1) and
      lymphocyte function-associated antigen-1 (LFA-1) molecules, respectively.
      Although both mAbs displayed moderate blocking activity in an in vitro mixed
      lymphocyte response assay, strong suppression was observed when anti-donor (rat)
      ICAM-1 mAb was combined with anti-recipient (mouse) LFA-1 mAb. Likewise,
      significant prolongation of islet xenograft survival was observed with these
      mAbs. Thus, 0.05 mg of anti-mouse LFA-1 mAb and anti-rat ICAM-1 mAb given on days
      0 and 1 produced significant prolongation of graft survival over the control
      (51+/-20 days vs. 10+/-3 days, P<0.0001), but not when anti-mouse ICAM-1 mAb was
      combined with anti-mouse LFA-1 mAb (13+/-3 days). In this species combination,
      mouse T cells were able to proliferate in the presence of rat antigen-presenting
      cells (APCs) in a cell number-dependent manner, but not in the presence of mouse
      APCs. The binding assay showed that LFA-1 molecules on mouse T cells can bind
      immobilized rat ICAM-1 molecules. These results suggest that rat ICAM-1 molecules
      on APCs can interact with mouse LFA-1 molecules on T cells across a species
      barrier and that this binding generates the consequent immune responses leading
      to rejection. mAb treatment against these adhesion molecules of recipient as well
      as donor is crucial for preventing rejection in a xenogeneic transplantation
      model.

PMID- 9583872
TI  - Determination of cell origin after marrow transplantation in canines by
      polymerase chain reaction and quantitation of the ZFY/ZFX genes.
AB  - BACKGROUND: In order to follow the course of bone marrow engraftment in dogs, and
      to determine the presence, and percentage, of donor-derived cells in other canine
      tissues, a simple and fast method of determining cell origin after sex-mismatched
      bone marrow transplantation was developed. METHODS: Using universal primers,
      fragments from genomic DNA corresponding to ZFX and ZFY genes were amplified by
      polymerase chain reaction. A restriction fragment length polymorphism, combined
      with densitometric analysis, was then used to distinguish and quantitate ZFY and
      ZFX sequences. Unknown samples were analyzed against standards of known mixtures
      of male and female DNA. RESULTS: Canine ZFY and ZFX genes were clearly resolved
      after amplification, digestion with HaeIII, and denaturing polyacrylamide gel
      electrophoresis. Microchimerism could be detected in male and female dog DNA
      samples derived from a range of fresh and frozen tissues including spleen,
      testicle, and the central nervous system. The levels of chimerism determined
      using this method were in either agreement with results obtained by karyotyping
      or more sensitive, with a detection limit of 0.4% compared with 1-2%.
      CONCLUSIONS: Polymerase chain reaction/restriction fragment length polymorphism
      detection of the ZFY and ZFX genes was found to be simple, accurate, and reliable
      for assessing engraftment in dogs. When compared with cytogenetic analysis, this
      method was found to be faster to perform, more capable of detecting lower levels
      of microchimerism, and useful for detecting donor-derived cells in stored
      specimens and in tissues other than peripheral blood or bone marrow.

PMID- 9583873
TI  - Increased expression of the novel molecule OX-2 is involved in prolongation of
      murine renal allograft survival.
AB  - BACKGROUND: Portal venous (p.v.) peritransplant immunization with dendritic cells
      from bone marrow cultures, along with cyclosporine (10 mg/kg), produces antigen
      specific increased renal allograft survival compared with recipients receiving
      intravenous (i.v.) immunization. Increased survival is associated with altered
      cytokine production from recipient T cells restimulated with donor antigen. We
      used a suppressive subtractive hybridization approach to explore a role in the
      regulation of transplant rejection for other genes differentially expressed after
      p.v. immunization. METHODS: Subtractive hybridization was performed using tissue
      from p.v. and i.v. immunized mice and a novel polymerase chain reaction-based
      approach. A gene-bank search was used to identify the source of the
      differentially expressed cDNAs. One product, the mouse homologue of rat OX-2, was
      further analyzed using Western gels and FACS analysis of dendritic cells
      (NLDC145+) isolated from p.v.-immunized mice. RESULTS: Eighty cDNA clones were
      obtained by suppressive subtractive hybridization. Differential expression was
      confirmed in Northern RNA blots. One clone showed sequence homology to a gene
      encoding a molecule on rat dendritic cells (MRC OX-2), with homology to genes
      encoding the costimulatory molecules CD80 (B7-1) and CD86 (B7-2). In p.v.
      immunized mice, a monoclonal antibody to the rat OX-2 molecule identified, by
      Western blot analysis, increased expression of a molecule with molecular weight
      (43 kDa) analogous to rat MRC-OX-2; labels (by FACS analysis) indentified
      increased numbers of a population of cells staining with NLDC145; and blocks
      indentified increased graft survival. CONCLUSION: Our data suggest that OX-2 is
      functionally important in the increased graft survival seen in p.v.-immunized
      mice receiving renal allografts.

PMID- 9583874
TI  - Patterns of allosensitization in allograft recipients: long-term cardiac
      allograft acceptance is associated with active alloantibody production in
      conjunction with active inhibition of alloreactive delayed-type hypersensitivity.
AB  - BACKGROUND: The immunologic characteristics of experimental allograft acceptance
      remain ill-defined. This study evaluates humoral and cell-mediated immunity in
      transiently immunosuppressed mice that have accepted cardiac allografts. METHODS:
      DBA/2-->C57BL/6 heterotopic cardiac allograft recipients were immunosuppressed
      with either GK1.5 monoclonal antibody or gallium nitrate and monitored for donor
      reactive delayed-type hypersensitivity (DTH) assessed by ear challenge and for
      alloantibody production detected by flow cytometry. RESULTS: Cardiac allograft
      function continued for >90 days in approximately 50% of GK1.5-treated and 97% of
      gallium nitrate-treated transplant recipients. All nonsuppressed recipients lost
      graft function within 7 to 10 days. Among mice that accepted allografts, donor
      reactive IgG was produced by about 50% of GK1.5 monoclonal antibody-treated mice
      and 80% of gallium nitrate-treated mice. None of the these mice exhibited donor
      reactive DTH responses, and all could down-regulate third-party DTH responses in
      a donor alloantigen-dependent manner. This down-regulation is not found in
      nonsuppressed allograft recipients or in naive mice. Importantly, transfer into
      SCID mice of splenocytes from mice that accepted allografts, but not naive
      splenocytes, provided them with a similar ability to accept cardiac allografts,
      even if the grafts co-expressed third-party alloantigens. CONCLUSIONS: IgG
      alloantibody production by murine cardiac allograft recipients is not a precise
      indicator of allosensitization leading to either cardiac allograft rejection or
      acceptance. However, expression of alloreactive DTH is a reliable indicator of
      allosensitization leading to acute rejection, and the absence of DTH in
      association with active DTH down-regulatory mechanisms is a reliable indicator of
      allograft acceptance in this experimental model. Thus, DTH analysis may hold more
      promise than alloantibody detection for clinical assessment of posttransplant
      immune status.

PMID- 9583875
TI  - Percutaneous thrombolysis and stent placement for the treatment of portal vein
      thrombosis after liver transplantation: long-term follow-up.
AB  - BACKGROUND: The durable use of percutaneous minimally invasive techniques for the
      treatment of portal venous thrombosis after liver transplant has not been widely
      described. This report illustrates two cases in which percutaneous thrombolysis,
      angioplasty, and endovascular stent placement were successfully used to treat
      portal vein thrombosis in patients with recent liver transplants. METHODS: Liver
      dysfunction was initially manifested by the elevation of liver enzymes or the
      development of marked ascites and confirmed in both cases by sonography and
      angiography. The occluded portal vein was accessed by either a transjugular
      transhepatic puncture or direct transhepatic catheterization. Intraportal
      thrombolytic infusion, angioplasty, and stent placement were accomplished without
      complication. RESULTS: At the most recent follow-up, portal vein patency had been
      maintained for 2.5 and 4.5 years. CONCLUSIONS: These results demonstrate the
      technical feasibility and long-term patency of angioplasty and endovascular stent
      placement for the treatment of portal vein thrombosis in liver transplant
      recipients.

PMID- 9583876
TI  - Decreased protein binding of mycophenolic acid associated with leukopenia in a
      pancreas transplant recipient with renal failure.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is rapidly hydrolyzed to its active
      metabolite mycophenolic acid (MPA), which is excreted by the kidney after
      undergoing glucuronidation to MPAG. MPAG has been shown to accumulate in patients
      with renal failure. MPA is extensively and avidly bound to human serum albumin.
      In vitro inhibition of the pharmacologic target, inosine monophosphate
      dehydrogenase, is dependent on free MPA. It has been demonstrated that high MPAG
      concentrations decrease MPA protein binding in vitro. In addition, the uremic
      state is associated with altered protein binding of many drugs. METHODS: We
      assessed free MPA, total MPA, and MPAG kinetics in a patient with renal failure
      receiving MMF for a pancreas transplant, who presented with signs of MMF
      toxicity. MPA, MPAG, and free MPA were measured by high performance liquid
      chromatography and a validated 14C-MPA ultrafiltration methodology. RESULTS: The
      MPAG area under the concentration curve (AUC) in this patient was extremely high
      (5899 microg x hr/ml). The total MPA AUC of 36.8 microg x hr/ml was within the
      range usually obtained in stable renal patients. The free fraction of MPA and the
      free MPA AUC were markedly elevated (13.8% and 5.07 microg x hr/ml,
      respectively). CONCLUSIONS: Patients with severe renal insufficiency may have
      markedly increased free MPA levels that may not be reflected in total MPA
      concentrations. These patients may be at increased risk for MMF-related toxicity.

PMID- 9583877
TI  - A sensitive assay for measuring alpha-Gal epitope expression on cells by a
      monoclonal anti-Gal antibody.
AB  - BACKGROUND: The assessment of a-gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R)
      expression on various cells and tissues is important for the prediction of anti
      Gal-mediated immune rejection of xenografts. This study describes an enzyme
      linked immunosorbent assay (ELISA inhibition assay) developed for this purpose,
      which uses the monoclonal anti-Gal antibody M86. METHODS: Cells at various
      concentrations were incubated overnight with M86 at 1/100 dilution. The cells and
      bound antibody were removed, and the residual antibody in the supernatant was
      measured in an ELISA assay with a-gal-bovine serum albumin as a solid phase
      antigen. The extent of a-gal epitope expression on cells correlates with the
      subsequent inhibition of M86 binding in ELISA. The inhibition binding curves at
      various cell concentrations were compared with those of a standard cell line with
      a known number of epitopes per cell. RESULTS AND CONCLUSIONS: The mouse IgM M86
      monoclonal antibody was highly specific for a-gal epitopes. Using this antibody
      in an ELISA inhibition assay with cells at a wide range of concentrations enables
      the detection of at least 5 x 10(4) and up to more than 5 x 10(7) a-gal epitopes
      per cell. This assay can be used also for the detection of a-gal epitopes on
      membranes from tissue homogenates, and thus it enables the determination of the
      extent of decrease in a-gal epitope expression in animals that are genetically
      manipulated to alter their carbohydrate make-up.

PMID- 9583878
TI  - Effects of cyclosporine and FK506 on in vitro high shear-induced platelet
      reactivity in rat and human non-anticoagulated blood.
AB  - BACKGROUND: The immunosuppressants cyclosporine and FK506 have been used
      successfully in clinical transplantation, but both agents have various side
      effects. We have previously found that cyclosporine is prothrombotic and that
      FK506 is antithrombotic in an in vivo system. The aim of the present study was to
      assess the effects of these agents on platelet reactivity and coagulation using
      an in vitro shear-induced hemostatic platelet plug-forming instrument, the
      hemostatometer. METHODS: A purpose-built hemostatometer was constructed in our
      laboratory. The effects of cyclosporine and FK506 on platelet reactivity and
      coagulation were assessed under high shear stress using non-anticoagulated rat
      and human blood. RESULTS: FK506 significantly inhibited both platelet reactivity
      and coagulation. Cyclosporine also significantly inhibited coagulation, but a
      proaggregatory effect was observed at a final blood concentration of 0.05 mg/ml.
      CONCLUSIONS: The present in vitro results support our previous in vivo findings
      regarding the prothrombotic and antithrombotic effects of cyclosporine and FK506,
      respectively.

PMID- 9583879
TI  - Development of anti-tissue antibodies in the rat liver transplant model.
AB  - BACKGROUND: The aim of this study was to analyze the humoral immune response
      associated with orthotopic liver transplantation in the rat liver transplant
      model, and in particular to test the presence of anti-tissue antibodies. METHODS:
      Rearterialized liver transplantations were performed in the Dark Agouti (DA)-to
      Lewis (LEW) and the LEW-to-DA rat strain combinations. Sera of recipients were
      analyzed by immunofluorescence (on DA and LEW organ sections) and by western
      blotting (with DA and LEW liver proteins). RESULTS: We have shown that liver (but
      not heart or skin) recipients develop a humoral response against non-MHC tissue
      antigens as evidenced (1) by a pattern of staining comparable to that described
      in human patients harboring anti-smooth muscle antibodies and (2) by the presence
      of donor liver peptides recognized in the sera of the recipient by Western
      blotting. CONCLUSIONS: These experiments indicate that orthotopic transplantation
      of a nonacutely rejected liver allograft is associated with the development of a
      previously undescribed anti-tissue antibody response that seems to be neither
      organ nor MHC restricted.

PMID- 9583880
TI  - Incidence of posttransplant erythrocytosis (PTE) in kidney graft recipients where
      the recipient of the contralateral kidney developed PTE.

PMID- 9583881
TI  - Inhibition of glutathione synthesis by adenosine: possible implications for
      development of liver preservation fluids.

PMID- 9583882
TI  - Kaposi's sarcoma in liver transplant recipients on FK506.

PMID- 9583883
TI  - Platelet antibody testing for evaluating immune thrombocytopenias.

PMID- 9583884
TI  - ASCP survey on placental examination. American Society of Clinical Pathologists.

PMID- 9583885
TI  - United States geographic bacteria susceptibility patterns. 1996 ASCP
      Susceptibility Testing Group. American Society of Clinical Pathologists.

PMID- 9583886
TI  - Telomerase expression in normal epithelium, reactive atypia, squamous dysplasia,
      and squamous cell carcinoma of the uterine cervix.
AB  - Telomerase activity has been detected in a broad range of human malignant
      neoplasms, and its expression may represent an essential step in the malignant
      transformation of tissues; however, the expression of telomerase in premalignant
      lesions remains relatively unexplored. We tested tissue sections of cervical
      squamous cell carcinomas and squamous intraepithelial lesions, samples of benign
      reactive atypia, and normal cervical mucosa from hysterectomy and cone biopsy
      specimens for the expression of telomerase. Mirror-image sections from each
      sample were paraffin embedded and processed for histologic analysis. The test
      samples of cervical tissue were crushed under liquid nitrogen, and telomerase
      activity was determined by the telomeric repeat amplification protocol.
      Telomerase activity was detected in 18 of 18 cases (100%) of invasive squamous
      cell carcinoma. Twenty-five of 26 samples (96%) of high-grade squamous
      intraepithelial lesion also tested positively for telomerase activity, including
      10 of 10 samples of moderate dysplasia, 12 of 13 samples of severe dysplasia, and
      3 of 3 samples of carcinoma in situ. Telomerase activity was detected in 14 of 25
      samples (56%) of low-grade squamous intraepithelial lesion and in 10 of 18
      samples (56%) of reactive atypia but was detected in only 9 of 50 samples (18%)
      of histologically normal cervical mucosa. These results suggest that telomerase
      expression may be a marker of premalignant and malignant squamous cell lesions of
      the uterine cervix, although it is also expressed in a high proportion of cases
      of reactive atypia.

PMID- 9583887
TI  - Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation
      recurrence in prostatic adenocarcinomas.
AB  - We examined whether the cell proliferation index by MIB-1, HER-2/neu gene
      amplification, Gleason grade, and pretreatment level of serum prostate specific
      antigen (PSA) correlated with postradiation recurrence (PRR) in patients with
      prostatic adenocarcinoma. Formalin-fixed, paraffin-embedded tissue sections from
      42 pretreated cases of prostatic adenocarcinoma (38 needle biopsy and 4
      transurethral resection specimens) were immunostained for MIB-1 (MMI, Ventana
      Medical Systems, Tucson, Ariz). HER-2/neu gene amplification was analyzed by
      fluorescence in situ hybridization using the Oncor unique sequence probe (Oncor,
      Gaithersburg, Md). The cell proliferation index by MIB-1 was determined by
      labeling index; levels of HER-2/neu were analyzed semiquantitatively. Twenty
      three of 42 patients (55%) were considered to have PRR on the basis of
      consecutive elevations of serum levels of PSA to greater than 1.5 ng/mL after
      completion of treatment (mean follow-up time, 33.4 months). The cell
      proliferation index correlated with PRR on both univariate and multivariate
      analyses. Of the 23 tumors that showed PRR, 18 (78%) revealed a high cell
      proliferation index, compared with 6 of 19 cases (32%) that showed no PRR. Twelve
      of 23 cases of prostatic adenocarcinoma (52%) in the recurrent group showed HER
      2/neu gene amplification, compared with 5 of 19 (26%) in the nonrecurrent group;
      these findings reached near significance on univariate analysis. Pretreatment
      levels of serum PSA also reached significance on multivariate analysis. In this
      preliminary study, the cell proliferation index by MIB-1 reached independent
      significance in predicting PRR in patients with prostatic adenocarcinoma, whereas
      HER-2/neu amplification by fluorescence in situ hybridization reached near
      significance.

PMID- 9583888
TI  - Additional mimics of mucinous mammary carcinoma: fibroepithelial lesions.
AB  - To determine the origin and nature of mucinlike material in fine-needle
      aspiration (FNA) smears of the breast in noncancerous breast lesions, we studied
      breast FNA smears from four patients. All smears contained epithelial cells
      floating in a mucinlike background, which raised suspicion for mucinous (colloid)
      carcinoma. Mucicarmine stain was performed on one smear from each case.
      Subsequent tissue biopsy specimens were studied using mucicarmine, periodic acid
      Schiff with and without diastase, and alcian blue stains at pH 2.7 and 0.9 on
      selected tissue sections. Correlation of the cytologic and histologic findings of
      each lesion was performed. The mucinlike background in all four FNA smears
      stained strongly with mucicarmine. Corresponding biopsy specimens revealed
      pseudoangiomatous hyperplasia in the first case, fibroadenoma and atypical ductal
      hyperplasia in the second, benign phyllodes tumor in the third, and fibroadenoma
      in the fourth. Each lesion in cases 1 to 3 was associated closely with
      fibrocystic changes. In case 4, cystic changes were located within the
      fibroadenoma. On tissue sections of all four cases, the cyst contents and 10% to
      50% of normal lobule and duct contents stained with mucicarmine, indicating that
      the cyst contents were the most probable source of mucin in the FNA smears. The
      presence of pools of mucicarmine-positive material in FNA smears of the breast is
      not an exclusive feature of mucinous carcinoma; mucicarmine-positive mucin can
      arise from benign cystic changes as well as from normal lobules and ducts.

PMID- 9583889
TI  - Clinicopathologic significance of transitional cell carcinoma pattern in
      nonlocalized ovarian epithelial tumors (stages 2-4).
AB  - The transitional cell carcinoma (TCC) pattern has been associated with favorable
      outcome in patients with late-stage ovarian epithelial tumors who receive
      chemotherapy. We examined the clinicopathologic significance of TCC and explored
      other histopathologic prognostic indicators for patients with ovarian epithelial
      tumor. The surgical records of patients at the University of California at Davis
      Medical Center who underwent treatment for stages 2 to 4 ovarian epithelial tumor
      were studied retrospectively; the histopathologic features were correlated with
      outcome. The TCC pattern was identified in 32 of 136 ovarian epithelial tumors
      (23.5%): 18 (13.2%) as a predominant (> 50%) and 14 (10.3%) as a focal (< or =
      50% but > 25%) histologic pattern. The other predominant histopathologic types
      were serous (65.4%), mucinous (11.7%), endometrioid (3.6%), clear cell (3.6%),
      and small cell (1.5%) carcinoma. Architectural grade was as follows: low
      malignant potential, 13 cases; grade I, 34 cases; grade II, 63 cases; grade III,
      26 cases. Nuclear grade was as follows: low grade, 27 cases; high grade, 109
      cases. One hundred seven patients had dominant ovarian tumors, and 29 had diffuse
      primary peritoneal epithelial tumor. One hundred twenty-three cases (90%) of
      peritoneal disease were invasive; 11 (10%) were noninvasive. Peritoneal disease
      histopathologic density was 50% or less cross-sectional involvement in 68
      patients (50%) and greater than 50% in 68 (50%). Follow-up data were available
      for 118 patients: 46 patients had persistent disease that was unresponsive to
      chemotherapy; 36 of these patients died of disease at 0 to 41 months (mean, 15.6
      months; median, 23.5 months). Ten patients were alive at 16 to 40 months (mean,
      24.5 months; median, 20.5 months). Thirty-six patients had recurrent disease
      after 6 to 66 months (mean, 23.5 months; median, 18.5 months); 20 of these
      patients died of disease after 10 to 69 months (mean, 33.7 months; median, 30
      months), and 16 were alive after 12 to 159 months (mean, 33.7 months; median, 30
      months). Thirty-six patients had no evidence of disease at 12 to 159 months of
      follow-up (mean, 49.5 months; median, 31 months). The TCC pattern, either
      predominant or focal, was not associated with disease status or survival time (P
      > .05). Predictors of recurrent or persistent disease and survival, respectively,
      were invasive peritoneal disease (P < .05, P < .0001) and greater than 50% cross
      sectional area histologic density of peritoneal disease (P < .01, P < .01).
      Grade, histologic type, and diffuse primary peritoneal vs ovarian location were
      not predictors of outcome. The TCC pattern was present in at least a focal (>
      25%) component in 23% of epithelial tumors; however, this finding did not reach
      significance as a predictor of outcome in this study. The histologic pattern of
      the peritoneal disease (invasiveness and density) was a much stronger predictor
      of disease response and survival.

PMID- 9583890
TI  - Novel subtyping of intestinal metaplasia in the human stomach: brain-type
      glycogen phosphorylase expression in the proliferative zone and its relationship
      with carcinogenesis.
AB  - Although reports have suggested the incomplete type of intestinal metaplasia (IM)
      had a close correlation with carcinoma, considerable data showed no apparent
      relationship between the particular type of IM and the intestinal type carcinoma.
      The purpose of this study was to establish a novel classification of IM using
      brain-type glycogen phosphorylase (BGP) from a carcinogenetic viewpoint. The only
      isoform expressed in gastric cancer was BGP using polymerase chain reaction
      analysis. We studied 136 specimens with gastric carcinoma and the adjacent IM
      using specific anti-BGP antibody with its correlation to subtypes of IM,
      proliferating cell nuclear antigen-labeling index, and various oncogene products.
      Brain-type glycogen phosphorylase was expressed in 80.5% of the intestinal type
      and 18.8% of the diffuse type of carcinoma and in 87.5% and 41.6% in the
      generative zone of IM adjacent to cancer foci, respectively, whereas no
      reactivity was observed in the normal gastric mucosa. The proportion of the
      positivity in the cancer and IM was significantly greater in the intestinal-type
      carcinoma than in the diffuse type. The expression of BGP in the generative cells
      of IM had no significant correlation with the conventional type of IM. Intestinal
      metaplasias with BGP expression were significantly higher in a proliferating
      state than in those without BGP, and some of them that were coexpressed
      accumulated p53 in the generative cells. The relationship between IM with BGP in
      the generative cells and intestinal-type carcinoma was apparently closer than the
      conventional subtype of IM and gastric cancer. Intestinal-type carcinoma might
      arise from some of these proliferating cells with BGP.

PMID- 9583891
TI  - Serum platelet antibody testing: evaluation of solid-phase enzyme immunoassay and
      comparison with indirect immunofluorescence.
AB  - We compared the ability of solid-phase enzyme immunoassay (SPEIA) with that of
      indirect immunofluorescence to detect serum platelet antibodies by parallel
      testing five sets of serum specimens: (1) 12 monospecific HLA class I specimens
      with defined specificities, (2) 4 HPA-1a specimens, (3) 164 sequential unselected
      specimens sent to our laboratory for serum platelet antibody testing, (4)
      specimens from 15 consecutive patients sent for indirect immunofluorescence
      testing alone, and (5) specimens from 19 consecutive patients sent for both
      indirect and direct immunofluorescence testing. In addition, specimens of HLA
      sera were tested by standard complement-dependent lymphocytotoxicity. Solid-phase
      enzyme immunoassay was consistently more sensitive than indirect
      immunofluorescence for all 12 HLA specimens and more sensitive than complement
      dependent lymphocytotoxicity for 11 of 12 specimens. Similarly, SPEIA was more
      sensitive than indirect immunofluorescence for all four HPA-1a serum specimens by
      one to three dilutions. In the nine presumed autoimmune cases (group 5), results
      were positive with SPEIA in one case; no positive results were noted with
      indirect immunofluorescence. The solid-phase enzyme immunoassay test permits
      ready differentiation between alloantibodies directed to HLA and those directed
      to platelet-specific glycoproteins.

PMID- 9583892
TI  - Minimum lyophilized plasma requirement for ISI calibration. European Concerted
      Action on Anticoagulation.
AB  - The minimum requirement of lyophilized plasma samples for a reliable
      International Sensitivity Index (ISI) was assessed by calibrations based on
      reducing numbers from a maximum of 60 depleted and 20 plasma samples from
      patients receiving coumarin using a manual technique and low ISI thromboplastin.
      The probability of achieving an international normalized ratio (INR) result
      within a clinically important range of 20% deviation has been assessed at
      European Concerted Action on Anticoagulation (ECAA) national laboratories in
      calibrations of ECAA reference thromboplastin against the certified prothrombin
      time (PT) with a reference thromboplastin. With conventional orthogonal
      regression using a certified PT and linear regression using certified INR,
      deviations and the coefficient of variation of the calibration slope increased
      with reduced numbers. The INR deviations became marked when the number of
      abnormal plasma samples was reduced to fewer than 20. Calibrations of 3 abnormal
      plasma samples and 1 lyophilized normal plasma sample gave a high incidence of
      deviations greater than 10% with an INR of 3.0. The study demonstrates that with
      both methods of analysis, an optimum minimum number of lyophilized plasma samples
      is needed for a reliable local ISI.

PMID- 9583893
TI  - An immunofluorescent assay for acute promyelocytic leukemia cells.
AB  - Sequential treatment with all-trans retinoic acid followed by chemotherapy
      significantly improves the long-term survival of patients who have acute
      promyelocytic leukemia (APL). Consequently, a simple and accurate test is needed
      to establish the diagnosis of APL and to identify those patients having a relapse
      of the disease. We describe an accurate, 2-hour indirect immunofluorescent assay
      for identifying APL cells in bone marrow specimens. The assay uses the PML (PG
      M3) murine monoclonal antibody that is directed against the amino-terminal
      portion of the PML gene product. We observed a distinctive, finely speckled
      pattern of fluorescence in the NB4 cell line (a positive control), as well as in
      15 clinical specimens that were confirmed to have APL by cytogenetic,
      cytochemical, and immunophenotypic studies, including four cases of microgranular
      variant of APL. By contrast, a coarse globular pattern of fluorescence was
      observed in 53 other clinical specimens that did not contain APL. When we
      performed dilution studies using artificial mixtures of APL cells with normal
      bone marrow cells, we detected as few as 5% APL cells in the mixture. Finally,
      there was complete concordance between the immunofluorescent assay and a
      polymerase chain reaction-based assay for the PML-retinoic acid receptor alpha
      chimeric gene in 12 other clinical specimens. We conclude that the
      immunofluorescent assay for PML protein is a rapid, sensitive, and accurate
      method for determining the presence of APL cells in clinical specimens. This
      assay therefore should be considered as a cost-effective alternative to other
      diagnostic tests, such as karyotyping or polymerase chain reaction, for the
      diagnostic evaluation of APL.

PMID- 9583895
TI  - The absolute neutrophil count: is it the best indicator for occult bacteremia in
      infants?
AB  - Occult bacteremia affects approximately 5% of febrile children ages 2 to 36
      months. Many physicians empirically treat children who have a temperature higher
      than 39 degrees C, a white blood cell (WBC) count of more than 15.0 x 10(9)/L,
      and no focus of infection with antibiotics. We undertook this investigation to
      better define predictive indicators for bacteremia. Specifically we were
      concerned with determining whether the absolute neutrophil count (ANC) is a
      better diagnostic indicator than the total WBC count and whether the manual
      differential (which includes a band cell count) is necessary or helpful. Three
      separate groups of patients aged 2 to 36 months were assessed retrospectively.
      Group A consisted of febrile children (temperature, > 39 degrees C) who had
      positive blood cultures (50 patients). Group B included febrile children
      (temperature, > 39 degrees C) who had negative blood cultures (59 patients).
      Group C, nonfebrile children admitted to the hospital was the control group (61
      patients). The ANC and the total WBC count were significantly higher in group A
      than in group B. Although they were equally sensitive, the ANC was more specific
      than the total WBC count. Band cell counts of greater than 10% and the percentage
      of total neutrophils also were greater in group A than in group B. The values for
      group C were not significantly different from those for group B. Although a total
      WBC count of 15.0 x 10(9)/L is currently used to identify children at risk for
      occult bacteremia, the ANC seems to be as sensitive an indicator and may be more
      specific. Our study demonstrated that (1) the WBC count is a good indicator of
      occult bacteremia, (2) the ANC is as sensitive as the WBC count and may be more
      specific, (3) automated ANCs are comparable to manual ANCs, and (4) the band cell
      count is insensitive as an indicator and does not add any predictive value.

PMID- 9583894
TI  - The immunophenotype of adult acute myeloid leukemia: high frequency of lymphoid
      antigen expression and comparison of immunophenotype, French-American-British
      classification, and karyotypic abnormalities.
AB  - Immunophenotyping has become common in the diagnosis and classification of acute
      leukemias and is particularly important in the proper identification of cases of
      minimally differentiated acute myeloid leukemia (AML-M0). To evaluate the
      immunophenotype of adult AML, 106 cases were studied by cytochemical analysis and
      by flow cytometry with a panel of 22 antibodies. The results were compared with
      the French-American-British (FAB) Cooperative Group classification, as well as
      with available cytogenetic data on each case. CD45, CD33, and CD13 were the most
      commonly expressed antigens (97.2%, 95.3%, and 94.3%, respectively). Lymphoid
      associated antigens were expressed in 48.1% of cases. CD20 was the most commonly
      expressed lymphoid antigen (17%), although often expressed in only a
      subpopulation of leukemic cells, followed by CD7 (16%), CD19 (9.8%), CD2 (7.5%),
      CD3 (6.7%), CD5 (4.8%), and CD10 (2.9%). Some immunophenotypes correlated with
      FAB type, including increased frequency of CD2 expression in AML-M3; lack of CD4,
      CD11c, CD36, CD117, and HLA-DR expression in AML-M3; increased frequency of CD20
      and CD36 expression and lack of CD34 expression in AML-M5; increased frequency of
      CD5 expression in AML-M5a; and increased frequency of CD14 expression in AML-M5b,
      when compared with all other AMLs (P < .05). When compared with AML-M5b, AML-M5a
      demonstrated a lack of CD4 expression and a high frequency of CD117 expression.
      Complete morphologic and cytogenetic agreement between AML-M3 and t(15;17) was
      present, and four of five cases of AML-M4Eo demonstrated inv(16). The remaining
      case of M4Eo was characterized by a 6;9 translocation, and two other inv(16)
      cases were not classified as M4Eo. Expression of CD2 was present in two t(15;17)
      cases and in one inv(16) case, but expression of this antigen was not restricted
      to AML cases with these karyotypic abnormalities. Similarly, expression of CD19
      was not specific for t(8;21) AML. All t(8;21) leukemias demonstrated M2
      morphology. With the exception of M3, M4Eo, and a subgroup of M2 leukemias, the
      FAB classification does not appear to define cytogenetically distinct disease
      groups in adult AML. Immunophenotypically distinct profiles were identified in
      the M3 and M5 morphologic groups of the FAB classification. Immunophenotyping
      studies are helpful in the determination of myeloid lineage. In general, however,
      they are not sufficiently specific alone to be useful in precisely identifying
      either FAB or cytogenetically defined disease subtypes.

PMID- 9583897
TI  - Analyzing method comparisons.

PMID- 9583896
TI  - The incidence of DNA aneuploidy in multiple myeloma does not correlate with stage
      of disease.
AB  - The bone marrow of 47 patients with multiple myeloma (MM), 2 patients with plasma
      cell leukemia, and 11 patients with monoclonal gammopathy of undetermined
      significance (MGUS) was analyzed by flow cytometry for the detection of DNA
      aneuploidy. The question to be addressed was whether a correlation exists between
      the incidence of DNA aneuploidy and the stage of disease. With one-parameter
      analysis of DNA staining, a DNA aneuploidy was detectable in 17 of 60 patients.
      The detection rate for DNA aneuploidies could be increased to 37 of 60 patients
      with the second method, the simultaneous measurement of DNA content in additional
      immunophenotyped cells (CD38 or B-B4). In MGUS and the early stages of MM, the
      discrepancy between both methods was higher than in stage III MM. There were no
      statistical differences in the incidence of DNA aneuploidy between MGUS or the
      early stages of MM and stage III MM (21/32 patients vs 16/26 patients). The CD56
      expression in plasma cells was significantly higher in cases of DNA aneuploidy
      (mean +/- SD, 64.7% +/- 33.65% vs 39.3% +/- 36.69%; P = .028). Comparing the
      ratio of diploid to DNA aneuploid with that of CD56+ to CD56- plasma cells, a
      correlation was found in MGUS (r = 0.7320) in the early stages of MM, I and II (r
      = 0.8023), but not in stage III MM. Based on these data, the dual-staining method
      for DNA content in immunophenotyped cells is preferred for the detection of DNA
      aneuploidy, especially in the early stages of MM and in MGUS. The clinical
      importance of a classification of DNA aneuploidy and CD56 antigen expression
      together is proposed for testing.

PMID- 9583898
TI  - Regional laboratory networks.

PMID- 9583900
TI  - Self-reported frequent mental distress among adults--United States, 1993-1996.
AB  - In the United States, an estimated 10% of persons have some recent disability
      from a diagnosable mental illness (e.g., schizophrenia, phobias, depression, and
      anxiety disorders), and up to 24% of adults have experienced a mental disorder
      during the preceding year. In 1997, the estimated cost of mental illness exceeded
      $150 billion for treatment, social services, disability payments, lost
      productivity, and premature mortality. However, information is limited about the
      overall prevalence of general mental distress, which can be associated with the
      incidence and prevalence of specific mental illnesses and conditions. This report
      describes differences in the prevalence of self-reported frequent mental distress
      (FMD) for noninstitutionalized adults in the United States for specific
      demographic groups and by state and age-sex group using data from the Behavioral
      Risk Factor Surveillance System (BRFSS) for 1993-1996. The findings indicate high
      prevalences of FMD among persons who are unemployed or unable to work, indicated
      a "separated" or "widowed" marital status, or had annual household incomes of
      <$15,000.

PMID- 9583899
TI  - Magnification of electron micrographs.

PMID- 9583901
TI  - Silicosis deaths among young adults--United States, 1968-1994.
AB  - Silicosis is a potentially fatal and typically chronic fibrotic lung disease
      caused by occupational exposure to respirable crystalline silica dust. In the
      United States, most silicosis-associated deaths occur among persons aged > or =
      65 years, often following many years of silica dust exposure. However, the
      continuing occurrence of silicosis deaths in young adults reflects relatively
      recent overexposures, some of sufficient magnitude to cause severe disease and
      death after relatively short periods of exposure. This report describes deaths
      among two young adults with silicosis and underscores the risk for deaths from
      silicosis at relatively young ages.

PMID- 9583903
TI  - 9th Asian Congress of Paediatrics. Hong Kong, 23-27 March 1997. Abstracts.

PMID- 9583902
TI  - Substance abuse and addiction--the need to know.

PMID- 9583905
TI  - 100 Years of Dementia Praecox. Symposium proceedings. San Juan, Puerto Rico, 6-7
      December 1996.

PMID- 9583906
TI  - The International Society for Heart and Lung Transplantation. 18th annual meeting
      and scientific sessions. Chicago, Illinois, USA. April 15-18, 1998. Abstracts.

PMID- 9583904
TI  - Current perspectives in the treatment of lung cancer. Conference proceedings.
      Dublin, Ireland, August 1997.

PMID- 9583907
TI  - Our seed corn.

PMID- 9583908
TI  - Symptomatic syndrome of inappropriate antidiuretic hormone secretion associated
      with azithromycin.

PMID- 9583909
TI  - Management of sickle cell disease. Acute chest syndrome is common in children
      before puberty.

PMID- 9583910
TI  - Future of preschool vision screening. Review article did not separate review and
      implementation processes.

PMID- 9583911
TI  - Future of preschool vision screening. The existence of a service is not evidence
      of its value.

PMID- 9583912
TI  - Separate R&D budget is needed for monitoring effects of new drugs.

PMID- 9583913
TI  - Resource allocation to health authorities. Lessons learnt many years ago have
      been forgotten.

PMID- 9583915
TI  - Rationing health care. Debate is needed about core range of health services that
      will be available.

PMID- 9583914
TI  - Intravascular volume optimisation during repair of proximal femoral fracture.
      Regional anaesthesia is usually technique of choice.

PMID- 9583916
TI  - Breast feeding does not always work. Bottle feeding may help babies develop
      sucking skills.

PMID- 9583917
TI  - Breast feeding does not always work. Women need support as they decide what is
      best for them.

PMID- 9583918
TI  - Are part time doctors better doctors. Continuity of care is likely to suffer.

PMID- 9583919
TI  - Are part time doctors better doctors? Fulfilled doctors are better doctors.

PMID- 9583920
TI  - Are part time doctors better doctors? Service depends on teamwork.

PMID- 9583921
TI  - US tobacco countries pull out of deal.

PMID- 9583922
TI  - Confidential tobacco documents enter public domain.

PMID- 9583923
TI  - Breast cancer trial stopped early.

PMID- 9583924
TI  - Left hemisphere of the brain is underactive in dyslexic people.

PMID- 9583925
TI  - The man who dared to foretell the future.

PMID- 9583926
TI  - Investigation by Parkinson's Disease Research Group of United Kingdom into excess
      mortality seen with combined levodopa and selegiline treatment in patients with
      early, mild Parkinson's disease: further results of randomised trial and
      confidential inquiry.
AB  - OBJECTIVE: To determine whether the excess mortality observed in patients who
      received both levodopa and selegiline in a randomised trial could be explained by
      revised diagnosis of Parkinson's disease, autonomic or cardiovascular effects,
      more rapid disease progression, or drug interactions. DESIGN: Open randomised
      trial and blind comparison and reclassification of the cause of death of patients
      who were recruited from 93 hospitals between 1985 and 1990 and who had died
      before December 1993 in arms 1 and 2. SETTING: United Kingdom. SUBJECTS: 624
      patients with early Parkinson's disease who were not receiving dopaminergic
      treatment and a subgroup fo 120 patients who died during the trial.
      INTERVENTIONS: Levodopa and a dopa carboxylase inhibitor (arm 1), levodopa and a
      dopa decarboxylase inhibitor in combination with selegiline (arm 2), or
      bromocriptine alone (arm 3). MAIN OUTCOME MEASURES: All cause mortality for 520
      subjects in arms 1 and 2 and for 104 subjects who were randomised into these arms
      from arm 3. Cause specific mortality for people who died in the original arms 1
      and 2 on the basis of the opinion of a panel, revised diagnosis and disability
      ratings, evidence from clinical records of either autonomic or cardiovascular
      episodes, other clinical features before death, and drug interactions. RESULTS:
      After extended follow up (mean 6.8 years) until the end of September 1995, when
      arm 2 was terminated, the hazard ratio for arm 2 compared with arm 1 was 1.32
      (95% confidence interval 0.98 to 1.79). For subjects who were randomised from arm
      3 the hazard ratio for arm 2 was 1.54 (0.83 to 2.87). When all subjects were
      included the hazard ratio was 1.33 (1.02 to 1.74) and after adjustment for other
      baseline factors it was 1.30 (0.99 to 1.72). The excess mortality seemed to be
      greatest in the third and fourth year of follow up. Cause specific death rates
      showed an excess of deaths from Parkinson's disease only (hazard ratio 2.5 (1.3
      to 4.7)). No significant differences were found for revised diagnosis, disability
      rating scores, autonomic or cardiovascular events, other clinical features, or
      drug interactions. Patients who died in arm 2 were more likely to have had
      possible dementia and a history of falls before death compared with those who
      died in arm 1. CONCLUSION: The results consistently show excess mortality in
      patients treated with combined levodopa and selegiline. Revised diagnosis,
      autonomic or cardiovascular events, or drug interactions could not explain this
      finding, but falls and possible dementia were more common in arm 2. The results
      do not support combined treatment in patients with newly diagnosed Parkinson's
      disease. In more advanced disease, combined treatment should perhaps be avoided
      in patients with postural hypotension, frequent falls, confusion, or dementia.

PMID- 9583928
TI  - Suicide in patients with stroke: epidemiological study.

PMID- 9583927
TI  - Randomised controlled trial of aminosidine (paromomycin) v sodium stibogluconate
      for treating visceral leishmaniasis in North Bihar, India.
AB  - OBJECTIVES: To assess the efficacy and tolerability of aminosidine compared with
      sodium stibogluconate for treating visceral leishmaniasis. DESIGN: Randomised,
      unblinded, controlled trial with 180 day follow up. SETTING: Kala-Azar Research
      Centre, Brahmpura, Muzaffarpur, Bihar, India. SUBJECTS: People of either sex aged
      6-50 years with symptoms and signs suggestive of visceral leishmaniasis (fever,
      loss of appetite, enlarged spleen) with leishmania amastigotes detected in Giemsa
      stained aspirates of spleen or bone marrow. INTERVENTIONS: Aminosidine at three
      daily doses (12, 16, and 20 mg/kg) for 21 days and sodium stibogluconate 20
      mg/kg/day for 30 days. MAIN OUTCOME MEASURES: Laboratory measures of efficacy:
      parasite count, haemoglobin concentration, white cell count, platelet count,
      serum albumin concentration. Clinical measures of efficacy: spleen size, fever,
      body weight, and liver size. Measures of safety: liver and renal function tests,
      reports of adverse events. RESULTS: Of the 120 patients enrolled (30 per
      treatment arm), 119 completed treatment and follow up. Cure at end of follow up
      was achieved in 23 (77%), 28 (93%), and 29 (97%) patients treated with 12, 16,
      and 20 mg aminosidine/kg/day respectively, and in 19 (63%) patients given sodium
      stibogluconate. At 16 and 20 mg/kg/day, aminosidine was significantly more active
      than sodium stibogluconate in both clinical and laboratory measures of efficacy.
      No significant clinical or laboratory toxicity occurred in any treatment group.
      CONCLUSIONS: A 21 day course of aminosidine 16 or 20 mg/kg/day should be
      considered as first line treatment for visceral leishmaniasis in Bihar.

PMID- 9583929
TI  - Qualitative research and evidence based medicine.

PMID- 9583930
TI  - Economic benefit analysis of primary prevention with pravastatin. Assumptions are
      methodologically flawed.

PMID- 9583931
TI  - Risk language and dialects. Lottery can be used to show risks.

PMID- 9583932
TI  - Risk language and dialects. Risk scales should be tested by non-medical agencies,
      such as the media.

PMID- 9583933
TI  - Patients with implants should be given implant cards. Such cards would facilitate
      recall.

PMID- 9583934
TI  - Mouth care and skin care in palliative medicine. Simple antiseptic mouthwashes
      are best for infection.

PMID- 9583935
TI  - Mouth care and skin care in palliative medicine. Clinically proved treatments for
      xerostomia were ignored.

PMID- 9583936
TI  - Musings on our meetings: MLA conventions, 'ninety-eight to date.
AB  - Annual meetings of the Medical Library Association have been a part of the
      culture of medical librarians in North America since 1898. With only four
      exceptions (one during WWI and three during WWII) medical librarians have met
      annually for nearly 100 years to conduct their business, share ideas, present
      papers, attend continuing education courses, view exhibits, and have fun. Based
      on the writer's research and personal experience, his reflections contain a
      summary of the history and development of these meetings since the first one in
      Philadelphia in 1898, an assessment of their content and value, and
      recommendations.

PMID- 9583937
TI  - Proceedings of the 21st International Symposium on High Performance Liquid Phase
      Separations and Related Techniques. Part I. Birmingham, United Kingdom, 22-27
      June 1997.

PMID- 9583938
TI  - Sensitive high-resolution analysis of biological molecules by capillary zone
      electrophoresis coupled with reflecting time-of-flight mass spectrometry.
AB  - Off-line and on-line capillary zone electrophoresis-electrospray ionization time
      of-flight mass spectrometry (CZE-ESI-TOF-MS) experiments were conducted using
      uncoated fused-silica capillaries coupled to a reflecting TOF mass spectrometer
      via a gold-coated sheathless interface. Off-line and on-line experiments were
      performed on standard mixtures of proteins and peptides. Samples collected off
      line electrokinetically in plastic vials were analyzed by standard ESI-TOF-MS at
      the pmol level. Sheathless CZE-ESI-TOF-MS was first simulated in an off-line
      experiment, using a test bench, in order to select a suitable running
      electrolyte, to find the optimal electrospray potential, and also to test the
      gold-coated capillary tips. This enabled an ease of transition to on-line
      measurements. On-line CZE-ESI-TOF-MS measurements of the total ion
      electropherogram (TIE) and of selected ion electropherograms (SIE) on peptide
      mixtures demonstrated fmol-level sensitivity, with S/N values of 250-400 on raw
      data (TIE mode) and of 30-760 (SIE mode). The use of reflecting TOF-MS afforded
      mass resolution values R>6000 (m/delta(m)(FVHM)) and enabled isotopic resolution
      of peptide components as well as mass accuracy in the 10 ppm range. These results
      were comparable with values observed with the usual ESI source on the same mass
      spectrometer, and thus demonstrated no loss in spectral quality from using the
      sheathless CE interface. On-line CE separation efficiency was equivalent to that
      obtained off-line for the separation of a peptide mixture, with N=35000-87000
      theoretical plates. Separations of standard proteins yielded equivalent mass
      spectral resolution and accuracy with separation efficiencies of N=2800-5500 and
      S/N values of 110-225 on raw data. The gold-coated sheathless CE-ESI interface
      was found to be relatively easy to prepare with the use of gold vapour
      deposition. The interface produced a stable electrospray for extended periods of
      time and was found to be robust and reliable.

PMID- 9583940
TI  - Current progress in neuroendocrinology of Germany. Erlangen, February 1998.
      Abstracts.

PMID- 9583939
TI  - The exosome: a versatile RNA processing machine.
AB  - A conserved complex of multiple 3'-to-5' exonucleases has been discovered
      recently in eukaryotes. This essential complex, the exosome, is required for
      diverse RNA processing events.

PMID- 9583941
TI  - Electrophysiological Studies in the Critical Care Unit. Symposium at the 31st
      annual meeting of the Canadian Congress of Neurological Sciences. London,
      Ontario, Canada. June 26, 1996. Abstracts.

PMID- 9583942
TI  - Prostate-cancer link sours IGF-1.

PMID- 9583943
TI  - [A case of dilated cardiomyopathy caused by myocardial microinfarcts in the
      course of polycythemia vera].
AB  - This article presents a case of 45-year-old man with polycythemia vera non
      diagnosed before. The first symptom of polycythemia vera was acute congestive
      heart failure which suggested diagnosis of myocarditis. Polycythemia vera was
      confirmed by raised hematocrit, significantly increased platelet count, normal
      oxygen saturation, score for leukocyte alkaline phosphatase (LAP)-130 and
      splemomegaly. Echocardiography revealed left ventricular histological. Coronary
      arteriography showed normal coronary arteries. Finding of histological
      examination of the endomyocardial biopsy were described as necrosis of myocytes
      and abnormal blood flow in very small coronary vessels. It was the main reason of
      dilated cardiomyopathy caused by microinfarcts in polycythemia vera.
      Hematological parameters were reduced to normal levels after hydroxyurea
      treatment. Digitalis and ACE-inhibitor therapy quickly improved cardiovascular
      status from III to II NYHA class.

PMID- 9583944
TI  - Codon usage and gene function are related in sequences of Arabidopsis thaliana.
AB  - In this paper, the relationship between codon usage and the physiological pattern
      of expression of a gene is investigated while considering a dataset of 815
      nuclear genes of Arabidopsis thaliana. Factorial Correspondence Analysis, a
      commonly used multivariate statistical approach in codon usage analysis, was used
      in order to analyse codon usage bias gene by gene. The analysis reveals a single
      major trend in codon usage among genes in Arabidopsis. At one end of the trend
      lie genes with a highly G/C biased codon usage. This group contains mainly
      photosynthetic and housekeeping genes which are known to encode the most abundant
      proteins of the vegetal cell. At the other extreme lie genes with a weaker A/T
      biased codon usage. This group contain genes with various functions which
      exhibits most of the time a strong tissue-specific pattern of expression in
      relation, for example, to stress conditions. These observations were confirmed by
      the detailed analysis of codon usage in the multigene family of tubulins and
      appear to be general in plant species, even as distant from Arabidopsis thaliana
      as a monocotyledonous plant such as maize.

PMID- 9583945
TI  - JADE: an approach for interconnecting bioinformatics databases.
AB  - To achieve the integration of biological data available on the World Wide Web and
      maintained in diverse sources such as GDB, Genbank or Acedb, we have developed a
      software called Jade. Jade allows programmers to create analytic tools and
      graphical user interfaces for one or more existing bioinformatics data sources.
      These tools can then be interchanged, compared and reused without making
      modifications in the data sources themselves. The system is implemented in the
      Java programming language and will run equally well on Macintosh, Windows or Unix
      workstations. Jade is free and can be used immediately by all interested parties.

PMID- 9583946
TI  - Molecular characterization of the Helicobacter pylori uvr B gene.
AB  - Helicobacter pylori persists in the human stomach where it may encounter a
      variety of DNA-damaging conditions, including gastric acidity. To determine
      whether the nucleotide excision repair (NER) pathway contributes to the repair of
      acid-induced DNA damage, we have cloned the putative H. pylori NER gene, uvrB.
      Degenerate oligonucleotide primers based on conserved amino acid residues of
      bacterial UvrB proteins were used in PCR with genomic DNA from H. pylori strain
      84-183, and the 1.3-kb PCR product from this reaction was used as a probe to
      clone uvrB from an H. pylori genomic library. This plasmid clone had a 5.5-kb
      insert containing a 2.0-kb ORF whose predicted product (658 amino acids; 75.9
      kDa) exhibited 69.5% similarity to E. coli UvrB. We constructed an isogenic H.
      pylori uvrB mutant by inserting a kanamycin-resistance cassette into uvrB and
      verified its proper placement by Southern hybridization. As with uvrB mutants of
      other bacteria, the H. pylori uvrB mutant showed a greatly increased sensitivity
      to the DNA-damaging agents methylmethane sulfonate and ultraviolet radiation. The
      uvrB mutant also was significantly more sensitive than the wild-type strain to
      killing by low pH, suggesting that the H. pylori nucleotide excision repair (NER)
      pathway is involved in the repair of acid-induced DNA damage.

PMID- 9583947
TI  - Characterization of the P25 silk gene and associated insertion elements in
      Galleria mellonella.
AB  - Insect silk genes attract attention by their precise territorial and
      developmental regulations and extremely high expression rates. Our present
      investigations demonstrated that the P25 silk gene of Galleria mellonella is down
      regulated by ecdysteroid hormones. The gene was identified within 5217
      nucleotides (nt) of two genomic clones. In contrast to other silk genes, Galleria
      P25 lacks the canonical TATA box. Transcription is initiated within a region of
      three nucleotides that lie at the end of a capsite initiator sequence ACAGT and
      about 90 nt downstream from a CAAT box. A stretch of 32 nt with a core sequence
      CTTTT was detected in the 5' region of Galleria P25 as well as in the presumptive
      regulatory regions of all other silk genes that are expressed in the posterior
      silk gland. However, consensus sequences reported for the regulatory regions of
      Bombyx silk genes are not obvious in Galleria P25. The coding sequence of this
      gene included 654 nt, is interrupted by 4 introns, and ends in position +3369; a
      potential polyadenylation signal starts at +4382. The gene contains 3 copies of a
      short interspersed nuclear element (SINE), which are located in the upstream
      region (-833 to -579) and in the first (+542 to +840) and second (+2259 to +2556)
      introns. The repeat, which was named Gm1, occurs in some other Galleria genes and
      exhibits homology to Bm1 SINE of the silkworm and to a similar element of a
      spider. Another insertion of at least 150 nt and with loosely defined borders is
      present in the 3' untranslated region (UTR) of Galleria P25. It includes a box
      (+3453 to +3552) of 99 nt that is tentatively called Lep1 because it was
      disclosed also in some other Lepidoptera. Lep1 seems to represent the core region
      of insertion elements that occur in the genomes of lepidopteran insects in
      various species specific and region specific modifications.

PMID- 9583948
TI  - Gene structure, expression in Escherichia coli and biochemical properties of the
      NAD+ -dependent glyceraldehyde-3-phosphate dehydrogenase from Pinus sylvestris
      chloroplasts.
AB  - Photosynthetic eukaryotes typically possess two distinct glyceraldehyde-3
      phosphate dehydrogenases, an NAD+ -specific enzyme in the cytosol (GapC: EC
      1.2.1.12) and an NADP+ -dependent enzyme in the chloroplast (GapAB: EC 1.2.1.13).
      The gymnosperm Pinus sylvestris is an exception in that it is known to express a
      gene encoding a transit peptide-bearing GapC-like subunit that is imported into
      chloroplasts (GapCp), but the enzymatic properties of this novel GAPDH have not
      been described from any source. We have expressed the mature GapCp unit from
      Pinus in Escherichia coli and have characterized the active enzyme. GapCp has a
      specific activity of 89 units per milligram and is strictly NAD+ -dependent,
      showing no detectable activity with NADP+. Values of the apparent Km for NAD+ and
      glyceraldehyde-3-phosphate were determined as 62 and 344 microM, respectively.
      The Pinus GapCpl gene possesses 12 introns, two in the region encoding the
      transit peptide and ten in the region encoding the mature subunit, all of which
      are found at positions strictly conserved across genes for higher plant GapC. A
      cDNA encoding a homologue of GapCp was isolated from the heterosporous fern
      Marsilea quadrifolia, indicating that NAD+ -dependent chloroplast GAPDH also
      occurs in other higher plants.

PMID- 9583950
TI  - Identification of Btr-regulated genes using a titration assay. Search for a role
      for this transcriptional regulator in the growth and virulence of Bordetella
      pertussis.
AB  - Bordetella pertussis is the causative agent of the respiratory disease pertussis
      or whopoping cough. Btr, an oxygen-responsive transcriptional regulator of B.
      pertussis, is homologous to the FNR protein of E. coli. Using a murine
      respiratory model, we observed in the present study that Btr is important in
      growth and survival of B. pertussis in vivo. A titration assay was developed that
      identified genes containing Btr binding sites including B. pertussis sodB and
      btr, E. coli aspA and a new B. pertussis gene, brg1. The brg1 gene encodes a
      protein similar to the LysR family of transcriptional regulators and its
      expression is activated threefold by Btr under anaerobic growth conditions but
      unaffected by Btr aerobically. The nucleotide sequence flanking brg1 encodes
      proteins with similarity to various metabolic enzymes. Putative overlapping
      promoters and a Btr binding site (FNR box) were identified in the DNA sequence
      between brg1 and the adjacent genes. These intervening sequences may represent
      sites for regulation by Btr and Brg1.

PMID- 9583949
TI  - cDNA cloning of Physarum polycephalum DNA topoisomerase I and expression analysis
      in plasmodia treated with cAMP.
AB  - cDNA encoding DNA topoisomerase I from Physarum polycephalum was isolated from a
      poly(A)+ -primed library (3'-region) and by PCR (5'-region). The coding region of
      cDNA was 3045 bp, encoding a polypeptide of molecular mass of 112 kDa. Identity
      between predicted amino acids sequences of conserved domains and corresponding
      domains from another eukaryotic type I DNA topoisomerases varied from 33.2 to
      53.5% for the core domain and from 33.8 to 57.4% for the C-terminal domain. A
      peculiar feature of Physarum DNA topoisomerase I was a stretch of repeated
      KPAX...X motifs in the N-terminal domain of the polypeptide. Although treatment
      of the plasmodia with db-cAMP increased relaxing activity of the DNA
      topoisomerase I several-fold, there was only a slight increase in the mRNA level.

PMID- 9583951
TI  - Sympatric mouse lemurs in north-west Madagascar: a new rufous mouse lemur species
      (Microcebus ravelobensis).

PMID- 9583952
TI  - Diet and feeding ecology of Ateles belzebuth belzebuth at Maraca Ecological
      Station, Roraima, Brazil.
AB  - The diet and feeding behaviour of habituated group of free-ranging spider monkeys
      (Ateles belzebuth belzebuth) were studied from 1987 to 1989. Their dietary
      patterns were analysed in relation to the temporal and spatial distribution of
      food resources. The results indicate that ripe fruit was regularly eaten
      throughout the study period and that diet composition was significantly related
      to the overall availability of ripe fruit sources.

PMID- 9583953
TI  - Planned parenthood and artifical selection.

PMID- 9583954
TI  - Comparative karyology in Akodon (Rodentia, Sigmodontinae) from Southeastern
      Brazil.
AB  - Karyotypic comparisons among five Akodon species showed that they shared a
      substantial proportion of their chromosome complements, indicated by distinct
      homologies between chromosomes, arms, or arm regions despite that this genus is
      karyotypically rearranged. A comparison with a related outgroup (Bolomys
      lasiurus) allowed for the recognition of ancestral and derived karyotypic traits
      as well as for inferring the direction of several chromosome rearrangements. This
      study indicated that species with lower diploid chromosome number are derived
      from species with higher diploid number, mainly by 11 fusions and 1 pericentric
      inversion while the direction of 5 other rearrangements could not be determined
      (fusions or fissions). UPGMA analyses of karyologic data indicated a topology
      like (Bolomys lasiurus (Akodon sp. (A. lindberghi (A. montensis (A. aff. cursor,
      A. cursor))))).

PMID- 9583955
TI  - The effect of mixed selected and unselected samples on the power of QTL mapping.
AB  - It is known from previous work that selection by truncation can lead to
      substantial loss of power to detect linkage with a QTL We examine the effect of
      mixed selected and unselected samples. We show that even if a modest proportion
      of the sample originates from an unselected population, this loss of power is
      quite effectively neutralized. Moreover, we reach the unexpected conclusion that
      if the selection intensity in the selected subpopulation is high, the power to
      detect QTL may actually increase.

PMID- 9583956
TI  - Comments on the paper by Willumsen et al. (1997)

PMID- 9583958
TI  - Water conservation and public health.

PMID- 9583957
TI  - Current aspects in cardiovascular care. Proceedings of the 4th International
      Mediterranean Symposium on Hypertension. Florence, Italy, 17-20 April 1997.

PMID- 9583959
TI  - 4th International Neurotrauma Symposium. Seoul, South Korea, August 23-26, 1997.
      Abstracts.

PMID- 9583960
TI  - Guidelines for unstable angina--application to African Americans.

PMID- 9583961
TI  - Cortisol: the aging hormone, the stupid hormone.

PMID- 9583963
TI  - Perpetuation of excellence. Inaugural address.

PMID- 9583962
TI  - Quality improvement and primary care manpower planning.

PMID- 9583964
TI  - Reducing Medicare and Medicaid entitlements: a contentious environment ensues.
AB  - Since our public officials now lack the courage and political will to raise taxes
      or to constrain Medicare and Medicaid benefits, we can expect that: 1) the
      private sector and future generations will pay an increasing share of these
      entitlements, 2) major cutbacks in Medicare, Medicaid, and health maintenance
      organization (HMO) reimbursement will result in the aged and poor experiencing
      decreased access to care and will hasten the current thrust of physicians,
      hospitals, and insurers forming powerful health networks, 3) these new regional
      alliances functioning as virtual monopolies will result in the public demanding
      that state-sponsored health services commissions be established, and 4) the
      weakest health networks, often in underserved areas, will be fiscally squeezed by
      inadequate reimbursement, so that by the turn of the century, many of these
      facilities and HMOs will seek bankruptcy protection as a means of restructuring
      their long-term debt.

PMID- 9583965
TI  - Modified recalcification time (MRT): a sensitive cancer test? Review of the
      evidence.
AB  - In the past, hypercoagulability causing cancer-related thrombosis (Trousseau
      phenomenon) remained unproven for lack of an appropriate coagulation test. This
      review proves that a modified recalcification time (MRT) test can detect cancer
      related hypercoagulability. The hallmark of this test involves incorporating
      tissue factor (TF) in accurately assessing coagulability. Blood from controls and
      cancer patients was incubated with saline and endotoxin (to enhance clotting
      ability by monocyte-generated TF). The MRT with saline incubation (MRTS) and the
      MRT with endotoxin incubation (MRTE) were determined instrumentally. The MRTE is
      a more inclusive measure of total TF activity than the MRTS in nonadvanced
      cancer. The MRTE values (minutes +/- standard deviation) were: controls-5.69 +/-
      0.8; miscellaneous cancers-3.17 +/- 1.1; head, neck, and colon cancers-3.9 +/-
      0.6; breast cancers-3.6 +/- 0.6; gynecological cancers-4.1 +/- 0.9; and prostate
      cancers-3.4 +/- 1.1. The MRTE, by demonstrating hypercoagulability in nonadvanced
      (including occult) cancer, qualifies as a more sensitive marker for cancer than
      the Trousseau phenomenon. The data suggest that this test may be the most
      sensitive blood test to detect early cancer.

PMID- 9583966
TI  - Isolation and analysis of nephritic-producing immune complexes in Plasmodium
      berghei-infected mice.
AB  - A nephritic condition was developed by infecting Swiss Webster albino mice with
      the malarial parasite Plasmodium berghei NK 65. These animals were tested for
      urinary protein and the presence of circulating immune complexes using reagent
      strips and a polyethylene glycol (PEG) precipitation assay. The circulating
      immune complexes were isolated from the sera using both affinity chromatography
      and PEG precipitation and from the kidney by acid elution. The isolated complexes
      were dissociated into their individual components and analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The components of the
      complexes were transferred to nitrocellulose sheets and probed for the presence
      of malarial antigens using a rabbit anti-P berghei antisera. The overall humoral
      response to the malarial parasite was evaluated using a radial immunodiffusion
      assay. The present study confirmed that the malarial-infected animals not only
      developed the nephritic condition (as evident by the high levels of proteinuria)
      but also, as indicated by the PEG assay, have the presence of high levels of
      circulating immune complexes in their serum. The apparent absence in the SDS gels
      of any abnormal protein bands followed by the inability of the Western blot to
      reveal any malarial antigens provides some of the strongest evidence to date that
      these malarial proteins are not directly involved in the circulating immune
      complexes believed to be responsible for producing this nephritic condition.

PMID- 9583967
TI  - Improving utilization of breast and cervical cancer screening in your office
      practice.
AB  - It has been well documented that early detection and early intervention for
      breast and cervical cancer saves lives. However, the challenge is to ensure that
      physicians' practices are effective in implementing the standard guidelines for
      screening and that all women are screened and undergo appropriate follow-up.
      Early detection and intervention are imperative since African-American women are
      twice as likely as European-American women to die from breast cancer even though
      the incidence of breast cancer is lower. African-American women have fewer
      mammograms and are being diagnosed later after metastases have occurred. Studies
      also show that women are more likely to have mammograms if their physicians so
      advise. However, the most common reason women give for not obtaining mammograms
      is, "My doctor never recommended it." By using a simple critical path analysis
      tool to systematically evaluate an office practice and by implementing practical,
      simple principles, a physician can increase utilization of breast and cervical
      cancer screening.

PMID- 9583968
TI  - Postvaccinial (influenza) disseminated encephalopathy (Brown-Sequard syndrome).
AB  - This article reports a case of Brown-Sequard syndrome that occurred in a patient
      following the administration of trivalent influenza vaccine. The patient
      responded well to intravenous steroids and physical therapy. This is the first
      reported case in the literature.

PMID- 9583969
TI  - Uveal melanomas in black patients: a case series and comparative review.
AB  - Uveal melanomas are rare in black patients. Of a total of 2586 patients with the
      diagnosis of posterior uveal melanoma who were managed in the Oncology Service at
      Wills Eye Hospital from 1974 to 1987, 10 patients (0.39%) were black. Data on
      patient age (mean: 53.9 years), sex (male-to-female ratio: 7:3), and relative
      frequency of disease between black (0.39% of total cases) and white patients were
      similar to that of previous reports. The distinguishing characteristics
      (incidence, risk factors, complications, and prognostic indicators) of uveal
      melanoma in black versus white patients also were reviewed.

PMID- 9583970
TI  - Normal arterial blood gas in a patient with saddle pulmonary artery embolus:
      diagnosis by transesophageal echocardiography.
AB  - This article describes a patient with a large, main pulmonary artery
      thromboembolus with normal arterial blood gas results, including normal alveolar
      arterial oxygen gradient. The diagnosis was established using transesophageal
      echocardiography and confirmed with pulmonary angiography. The patient
      subsequently underwent anticoagulation and eventually was discharged without
      complications.

PMID- 9583971
TI  - An open letter to the American Red Cross. 1942.

PMID- 9583973
TI  - House calls.

PMID- 9583972
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 15-1998. A 34-year-old woman with confusion and visual loss
      during pregnancy.

PMID- 9583974
TI  - House calls.

PMID- 9583975
TI  - House calls.

PMID- 9583976
TI  - House calls.

PMID- 9583977
TI  - House calls.

PMID- 9583978
TI  - Prophylactic platelet transfusions in acute myeloid leukemia.

PMID- 9583979
TI  - Prophylactic platelet transfusions in acute myeloid leukemia.

PMID- 9583980
TI  - Absence of toxicity of oats in patients with dermatitis herpetiformis.

PMID- 9583981
TI  - Loss of vision in Gaucher's disease and its reversal by enzyme-replacement
      therapy.

PMID- 9583982
TI  - Inappropriate drug-donation practices in Bosnia and Herzegovina.

PMID- 9583983
TI  - Inappropriate drug-donation practices in Bosnia and Herzegovina.

PMID- 9583984
TI  - Inappropriate drug-donation practices in Bosnia and Herzegovina.

PMID- 9583985
TI  - Inappropriate drug-donation practices in Bosnia and Herzegovina.

PMID- 9583987
TI  - Masked peer review revisited.

PMID- 9583986
TI  - A most attractive nose.

PMID- 9583988
TI  - [The hospitalized elderly and aged].

PMID- 9583989
TI  - Natural immunological tolerance: on time and space again.

PMID- 9583990
TI  - A short history of time and space in immune discrimination: reply to the
      commentaries.

PMID- 9583991
TI  - Neonatal tolerance to alloantigens is induced by enriched antigen-presenting
      cells.
AB  - Spleen and bone marrow cells from normal or Rag-1-deficient donors are equally
      competent in their ability to induce neonatal transplantation tolerance in semi
      allogeneic hosts, and the latter are also capable of tolerizing fully allogeneic
      recipients. Both types of donor cells resulted in comparable levels of
      haemopoietic chimerism in tolerant animals. Lymphoid hyperactivity, however, was
      absent in animals tolerized with Rag-1-deficient cells. The authors conclude that
      neonatal tolerance induced with haemopoietic cells requires no donor lymphocytes,
      and is thus not the result of deficient antigen presentation. Furthermore, the
      state of tolerance can be dissociated from the lymphoid hyperactivity that
      requires donor lymphocytes and is regularly scored in conventionally tolerized
      animals.

PMID- 9583992
TI  - Alpha1-microglobulin and bikunin in rats with collagen II-induced arthritis:
      plasma levels and liver mRNA content.
AB  - The plasma proteins alpha1-microglobulin (alpha1-m) and bikunin are synthesized
      in the liver as a common precursor which is cleaved just before secretion. Half
      of plasma alpha1-m is covalently linked to fibronectin and alpha1-inhibitor-3,
      and more than 95% of bikunin is part of pre-alpha-inhibitor, inter-alpha
      inhibitor and related large molecules. Both alpha1-m and bikunin have been shown
      to be involved in inflammation, but the regulation of their synthesis is not
      clear. The authors have measured the plasma and urinary concentrations of alpha1
      m and bikunin as well as their hepatic mRNA levels in rats during the development
      of collagen-induced arthritis. Also, the plasma concentrations of acknowledged
      acute-phase proteins were measured. The results suggested a biphasic inflammatory
      reaction: an early response after 1 week, represented by an elevated fibronectin
      level; and a late response after 3 weeks, represented by elevated alpha1-acid
      glycoprotein and decreased albumin and alpha1-inhibitor-3 levels. The alpha1-m
      bikunin mRNA content in liver was slightly reduced after 1 week and elevated
      after 3 weeks, but the total concentrations of free and bound alpha1-m and
      bikunin in plasma were unchanged. The free bikunin fraction as well as the
      fibronectin/alpha1-m complex in plasma, however, were elevated after 1 week.
      Urinary bikunin levels were also elevated after 1 week, whereas urinary alpha1-m
      levels remained unchanged. The results thus suggest that free bikunin in plasma
      is increased and excreted in the urine at an early stage during the development
      of collagen-induced arthritis. Later, when the synthesis rate of alpha1-m-bikunin
      is elevated, both proteins are most likely directed to other locations in the
      body.

PMID- 9583993
TI  - Interleukin-2 (IL-2) receptor alpha, beta and gamma subunit expression as a
      function of B-cell lineage ontogeny: the use of IL-2-PE66(4Glu) to characterize
      internalization via IL-2 receptor subunits.
AB  - Interleukin-2 (IL-2) is a pluripotent cytokine which plays a crucial role in the
      immune system response. Although the IL-2/IL-2 receptor (IL-2R) system has been
      well characterized in cells of the T lineage it is less known in B lymphocytes.
      The authors therefore studied the expression of the IL-2R alpha, beta and gamma
      subunits in human B-cell lines at different stages of maturation, by the
      polymerase chain reaction technique. The authors found that the alpha and beta
      subunits are expressed in the final stages of B-cell lineage maturation, whereas
      the gamma subunit is constitutively expressed during B-lymphocyte
      differentiation. The results indicate that the IL-2/IL-2R system, most probably,
      does not have a role in the early stages of B-cell differentiation, but may be
      involved only in the final stages of B-cell lineage ontogeny. Moreover, the
      ability of the different forms of IL-2R to internalize the IL-2 ligand was
      investigated, using the chimeric protein IL-2-PE66(4Glu). Cell lines bearing the
      alphagamma, betagamma and alpha betagamma forms of IL-2R were inhibited by the
      chimeric protein, while those bearing the gamma subunit alone did not respond to
      the chimera. Thus, internalization of IL-2 is most likely mediated via the
      alphagamma form of the IL-2R, as shown here for the first time, as well as
      through the betagamma and alpha betagamma IL-2R forms. However, IL-2 cannot be
      internalized through the IL-2R gamma subunit alone.

PMID- 9583994
TI  - Peptide binding to MHC class I is determined by individual pockets in the binding
      groove.
AB  - H-2Kb and HLA-A2 are MHC4 class I molecules with a similar overall structure.
      Important differences between these two class I molecules reside in the structure
      of the individual pockets in the antigenic-peptide-binding groove. H-2Kb, which
      has a deep C pocket, binds specifically peptides with a tyrosine or a
      phenylalanine at position 5. In contrast, HLA-A2 has a shallow C pocket, which
      cannot accommodate large side chains at position 5. Site-directed mutagenesis was
      used to generate a chimera between the murine H-2Kb and the human HLA-A2 [H
      2Kb/HLA-A2(C')]. The structure of this chimera is similar to H-2Kb except for the
      region around the deep C pocket, where residues at positions 9, 97 and 99 were
      substituted with those bulkier residues from HLA-A2. Peptide binding between this
      chimera and H-2Kb-binding peptides [VSV (52-59), OVA (257-264), and MCMV pp89
      (168-176)], revealed that the deep C pocket of H-2Kb was crucial for high
      affinity binding. While a peptide, VSV (52-59), was found to bind with
      severalfold lower 'affinity' to H-2Kb/HLA-A2(C') than to the wild-type H-2Kb, a
      VSV analogue with the tyrosine in position 5 (Tyr5) substituted with an alanine
      was found to bind with a similar 'affinity' to both MHC class I molecules.
      Computer-aided modelling of the H-2Kb/HLA-A2(C') complex indicates that the VSV
      (52-59) peptide probably binds to the chimeric MHC molecule with the peptide side
      chain of anchor residue Tyr5 pointing away from the groove. These results confirm
      a role of the individual pockets in determining peptide-binding affinity and
      specificity and suggest that this may be accomplished by changes in side-chain
      orientation.

PMID- 9583995
TI  - Severe graft-versus-host disease in SCID mice is associated with a decrease of
      selective donor cell TCR Vbeta specificities and increased expression of IFN
      gamma and IL-4.
AB  - Differences in T-cell selection and severity of graft-versus-host (GVH) disease
      were observed in immunodeficient C.B-17 SCID (SCID) mice after injection of
      allogeneic T lymphocytes from CBA/J or C57B1/6 (B6) mice. Infiltrating donor
      cells were analysed in bone marrow (BM), liver and spleen of newborn recipients
      and 5 days post-engraftment the number of B6 cells significantly exceeded that of
      CBA/J cells in these organs. At that time, cells in BM of B6 and CBA/J injected
      recipients were augmented in intracellular IL-4, IL-10, and TNF-alpha, whereas
      only cells in B6 treated BM were increased in IFN-gamma, and both treated groups
      of mice had up-regulated endogenous MHC class I and class II expression in the
      three organs. Already on day 5, and more pronounced day 10, B6 treated SCIDs had
      a relative decrease of four different TCR-Vbeta specificities among donor cells,
      whereas CBA/J injected mice had an abnormal expansion of Vbeta14+ donor T cells
      10 days post injection. At the same time, the total cell contents of BM and
      spleen of B6 injected mice were substantially decreased, and this was paralleled
      by signs of severe GVHD; whereas SCIDs treated with CBA/J exhibited much milder
      symptoms. Moreover, adult SCID mice injected with Vbeta2, 4, 8 and 14 depleted B6
      T cells showed an increased percentage of infiltrating donor cells and an
      enhanced decrease in BM cell content compared to SCIDs treated with total B6 T
      cell repertoire. In vitro, the Vbeta2, 4, 8 and 14 depleted population was more
      responsive to SCID spleen stimulators. Thus, a disturbed immunoregulation among
      donor T cells, caused by multiple changes in the TCR repertoire, may be
      responsible for inducing the severe GVHD.

PMID- 9583996
TI  - Surface properties of antigen-antibody complexes.
AB  - In this paper, the authors show that liquid-liquid partition chromatography in an
      aqueous two-phase system offers unique possibilities of comparing the overall
      surface properties of intact antibodies in solution before and after binding of
      antigen. The authors demonstrate that the surface properties of antigen-antibody
      complexes are dependent on the variable regions of the antibodies, the nature of
      the antigen and/or possible conformational changes induced by antigen binding.
      Thus, each antigen-IgG antibody pair formed one type of complex with respect to
      the exposed dominant surface. The antigen-binding sites of IgG antibodies were
      exposed and dominant even after binding of hapten or hapten-carrier. In contrast,
      the antibody-combining sites were concealed upon protein binding and the exposed
      surfaces of the protein-antibody complexes were related mainly to those of the
      antigen. IgA1, IgA2, IgE and IgM formed, in comparison to the IgG, hapten
      antibody complexes which exhibited surface properties that could be related to
      both the antigen-binding sites and Fc parts of the antibodies. Moreover, the
      results indicated that antigen-induced conformational changes occurred in either
      IgA1, IgA2, IgE, or IgM, but not in IgG1, -2, -3 and -4, making the surfaces of
      their heavy chain constant regions more similar.

PMID- 9583997
TI  - Changes in the specificity of antibodies in mice infected with lactate
      dehydrogenase-elevating virus.
AB  - Infection with lactate dehydrogenase-elevating virus (LDV) modifies the isotypic
      distribution of antibodies (Ab) directed to several antigenic proteins with a
      preferential production of IgG2a. Because it was not known whether the virus
      could also affect the Ab specificity, the authors addressed this point using
      human growth hormone (hGH) as a model antigen. Anti-hGH monoclonal antibodies
      (MoAb) were used as probes to study the occurrence of Ab to three native hGH
      epitopes (3C11, F11 and 10D6) in sera from LDV-infected CBA/Ht and BALB/c mice
      immunized with hGH. Competition ELISA was used to determine the extent of Ab
      directed to cryptic hGH epitopes, i.e. antigenic determinants hidden in the
      native hormone. Results indicated that in LDV-infected CBA/Ht mice the titres of
      anti-hGH Ab were lower than in controls, although a consistent isotypic shift to
      IgG2a subclass was observed. Concurrently, the presence of Ab to epitopes 3C11,
      F11 and/or 10D6 were markedly reduced in infected animals and most anti-hGH Ab
      were directed to hGH cryptic epitopes. By contrast, LDV infection increased the
      amount of anti-KLH Ab elicited by CBA/Ht mice and did not affect Ab specificity,
      whilst control and LDV-infected BALB/c mice showed similar concentrations of anti
      hGH Ab. Furthermore, the proportion of Ab to cryptic hGH epitopes did not change
      in infected animals even though an important shift to IgG2a was detected. Thus,
      data presented herein suggest that LDV infection modifies Ab specificity
      depending on the mice genetic background and on the antigenic characteristics of
      the immunogen.

PMID- 9583998
TI  - Generation and characterization of rat monoclonal antibodies against human serum
      amyloid A.
AB  - Monoclonal antibodies against human serum amyloid A (SAA) were generated in rat
      (which seems not to have mature SAA proteins) by immunizing intact human SAA.
      Thirteen clones selected by initial screening were analysed based on reactivity
      with synthetic peptides of SAA and with carboxyl-terminal truncated recombinant
      SAA. Antibodies were divided into four types, i.e. those recognizing the area
      around residue 18, 30, 90, and 100, respectively, of SAA. The antibody to the
      carboxyl terminus (around residue 100) of SAA, when subjected to
      immunohistochemistry for amyloid deposits in specimens from patients with
      reactive amyloidosis, always yielded negative reactivity, supporting the general
      concept that the carboxyl terminus of SAA is absent from human AA deposits.

PMID- 9583999
TI  - Electrophoretic polymorphism of a hamster pentraxin, female protein (amyloid P
      component).
AB  - Serum amyloid P protein (SAP) is a ubiquitous vertebrate protein distinguished by
      its conservative evolution and paucity of polymorphic forms. The SAP homologue in
      the Syrian hamster (Mesocricetus auratus), called Female Protein [FP(SAP)] is
      unique because its synthesis is controlled by sex hormones. These observations
      were limited to the commercially available standard Syrian hamsters that are
      descendants of three littermates captured in Syria in 1930. The authors examined
      FP(SAP) expression in nine inbred lines of Syrian hamsters that were derived from
      12 wild hamsters captured in 1971. In general, regulation of FP(SAP) was similar
      in the new wild hamster strains, although a novel electrophoretically slower
      FP(SAP) was found in three of the strains. The slow FP(SAP) was not distinguished
      by size, antigenicity, binding capacity, or regulation. The electrophoretic
      difference was still apparent after deglycosylation. Hybrid offspring coexpressed
      both fast and slow FP monomers and formed a unique hybrid pentamer that had a new
      mobility between the fast and slow parent FP(SAP). The origin of this unusual
      polymorphism could be related to the amyloidogenesis associated with expression
      of FP(SAP) in the standard Syrian hamster.

PMID- 9584000
TI  - Reactivity patterns of synovial T-cell lines derived from a patient with
      rheumatoid arthritis. I. Reactions with defined antigens and auto-antigens
      suggest the existence of multireactive T-cell clones.
AB  - The functional T-cell repertoire in the inflamed joint of a patient with
      rheumatoid arthritis was analysed at the clonal level. Using limiting dilution
      techniques and selecting for growth of in vivo activated and/or autoreactive T
      cells, 149 T-cell lines were established. They were tested in a proliferation
      assay for reactivity against an autologous Epstein-Barr virus (EBV)-transformed B
      cell line and a panel of auto-antigens and foreign antigens. Seventy-five lines
      (approximately 50%) could be stimulated. Thirty-six lines (approximately 24%)
      were antigen-reactive. They were stimulated by human collagens type I (15), II
      (10), IV (7) or V (4), cartilage proteoglycans (4), Mycobacterium tuberculosis
      (15), the 60 kDa heat-shock protein of M. bovis (13) or tetanus toxoid (10). T
      cell lines were either monoreactive (19), bireactive (6), or multireactive (11),
      i.e. they were stimulated by either one, by two, or by more antigens in the
      panel. About half of the antigen-reactive lines were at the same time
      autoreactive towards the autologous B-cell line. These data suggest the existence
      of multispecific autoreactive T-cell receptors comparable to multireactive or
      natural autoantibodies and prove the presence of autoantigen-reactive T cells in
      the inflamed joints of patients with rheumatoid arthritis.

PMID- 9584001
TI  - Perivascular T cells express the pro-inflammatory chemokine RANTES mRNA in
      multiple sclerosis lesions.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system (CNS), characterized by accumulation of mononuclear cells. The
      pathogenesis of MS is complex and probably involves soluble immune mediators,
      particularly cytokines, and activated memory T cells, that are thought to migrate
      into the CNS. During lesion formation in MS, cytokines regulate cell functions,
      such as cell recruitment and migration. Because the chemokine RANTES play a role
      in both activating and recruiting leucocytes, particularly memory T cells into
      inflammatory sites, the authors have assessed RANTES mRNA levels at the site of
      lesions. Expression levels were analysed in brain samples and compared with
      neurological, infectious and other controls. RANTES was expressed by activated
      perivascular memory T cells, predominantly located at the edge of active plaques.
      While RANTES mRNA was detected in all 17 MS brains analysed, it was only found in
      six of the 14 control patients and generally at a lower expression level. In view
      of the regulatory and chemotactic properties of RANTES, these results imply that
      RANTES in MS lesions may play an important role in the activation and/or
      selective accumulation of memory T cells and, thereby, in the pathogenic events
      associated with MS.

PMID- 9584002
TI  - Mannan-binding lectin in the sub-Saharan HIV and tuberculosis epidemics.
AB  - Inherited deficiency of mannan-binding lectin (MBL) has been shown to predispose
      to infections. Conversely, it has also been suggested that MBL might facilitate
      the uptake of certain intracellular microbes. The aim of this study was to
      investigate whether MBL plays a role in the HIV and tuberculosis epidemics in
      Africa. Thus, the authors determined the MBL serum concentration in 173 HIV
      infected patients (150 with concomitant tuberculosis), 94 patients with
      tuberculosis without being HIV infected, and 113 controls from Tanzania. The
      frequency of MBL deficiency was significantly increased in HIV infected patients
      compared with controls (12.1% and 3.5%, respectively). The frequency of patients
      deficient of MBL did not differ between controls and HIV negative patients with
      tuberculosis. However, HIV negative patients with tuberculosis had significantly
      higher MBL levels than both controls and HIV infected patients with or without
      tuberculosis. These results indicate that low levels of MBL are associated with
      increased risk of sexually transmitted HIV infection in Africans. By contrast,
      high levels of MBL may be involved in the pathogenesis of tuberculosis in
      immunocompetent individuals.

PMID- 9584003
TI  - T cell subsets and T cell function in cartilage-hair hypoplasia.
AB  - Cartilage hair hypoplasia is a rare autosomal recessive form of short-limbed
      dwarfism associated with a cellular immunodeficiency. In eight patients, the
      authors studied the presence of T cell subsets and in vitro T cell function in
      order to address the basis for the immunological disorder. Both the proliferative
      response to phytohaemagglutinin (PHA) and the PHA-induced IL2 production were 60%
      lower compared with controls (P = 0.007 and 0.005, respectively). The impaired
      proliferative response could not be restored by addition of IL-2. This result is
      in accordance with a decrease in the percentage of activated T cells expressing
      the p55 subunit of the IL-2 receptor complex (CD25). The results define more
      precisely that T cells from cartilage hair hypoplasia patients are defective in
      the transition from the G0 to the G1 phase of the cell cycle. Furthermore, the
      data demonstrate that several CHH patients show a reduced proportion of CD45RA+
      'naive' T cells. However, the in vitro impairment of T cell function cannot
      solely be explained by imbalance between 'naive' and 'memory' T cells. Although
      CHH patients with a history of recurrent respiratory tract infections showed the
      most aberrant in vitro immune parameters, a clear relationship between clinical
      data and in vitro parameters could not be established for the whole patient
      group.

PMID- 9584005
TI  - Selected papers from the 7th International Symposium on Medical Geography.
      Portsmouth, United Kingdom.

PMID- 9584004
TI  - On the non-poisonous death of Napoleon.

PMID- 9584006
TI  - Extraspinal causes of sciatica. A case report.
AB  - STUDY DESIGN: A case of intrapelvic aneurysm is reported. It is as an example of
      one of the many extraspinal causes of sciatica. OBJECTIVE: To demonstrate the
      importance of clinical examination in the assessment of patients with sciatic,
      despite continuing improvements in methods for imaging the spine. SUMMARY OF
      BACKGROUND DATA: Extraspinal conditions cause sciatic in a rare but recognized
      group of patients. Their clinical symptoms can be very similar to those of
      patients with sciatic from lumbar disc protrusion. METHODS: The clinical
      appearance, investigation, and treatment of a patient with an internal iliac
      artery aneurysm causing sciatic are discussed. RESULTS: Surgical treatment of the
      patient's aneurysm resulted in relief of the symptoms of sciatica. CONCLUSIONS:
      Although these cases are unusual in isolation, together they represent an
      important group. When a patient has sciatica, the clinician looks first to the
      spine for the origin of symptoms. Extraspinal causes are often not considered in
      the differential diagnosis. This oversight may be compounded by observation of
      asymptomatic disc protrusions on computed tomographic and magnetic resonance
      studies. The importance of clinical history and examination in the diagnosis of
      these lesions cannot be overemphasized.

PMID- 9584007
TI  - Diagnostic accuracy of technologies used in LBP assessment.

PMID- 9584008
TI  - Eighth World Conference on Lung Cancer, Dublin, August 1997.

PMID- 9584009
TI  - Mastectomy.

PMID- 9584010
TI  - [Problematic aspects of the Structural Health Regulation and minimal invasive
      surgery].
AB  - Decisions in surgery will have to consider economic obligations more than ever
      before. Consequences are evident: the assessment of surgical efficiency will be
      insufficient when only considering the accuracy and results of a clinical study.
      We actually will have to document, moreover, the economic impact of therapeutic
      procedures, particularly with respect to minimally invasive surgery.

PMID- 9584011
TI  - Consensus statement update on depression in late life is issued by the NIH.

PMID- 9584012
TI  - A Voluntary Smokers' Registry: Characteristics of joiners and non-joiners in the
      Community Intervention Trial for Smoking Cessation (COMMIT).
AB  - OBJECTIVES: This paper examines differences between joiners and nonjoiners of a
      voluntary smokers' registry. METHODS: A baseline prevalence survey was used to
      identify characteristics of smokers who joined or did not join a smokers'
      registry. RESULTS: Communities varied significantly in registry enrollment rates.
      Heavy-smoking joiners expressed more desire to quit, were more likely to live
      with nonsmokers, and were older than nonjoiners. Light-to-moderate joiners smoked
      more, were more addicted to cigarettes, and expressed more desire to quit than
      nonjoiners. CONCLUSIONS: Few baseline characteristics differentiated joiners from
      nonjoiners. Nonjoiners were significantly more likely to achieve cessation than
      joiners.

PMID- 9584013
TI  - Predictors of smoking among US college students.
AB  - OBJECTIVES: This study explored predictors of smoking among a large,
      representative national sample of students enrolled in American 4-year colleges.
      METHODS: A sample of undergraduate students, randomly selected from 140 colleges,
      was sent a detailed questionnaire that included questions about smoking status.
      RESULTS: The 30-day smoking prevalence was 22.3%; 25% of the participants were
      former smokers. Multivariate analyses suggested that, among college students, men
      are less likely to smoke than women. In addition, high-risk behaviors (e.g.,
      marijuana use) and lifestyle choices (e.g., nonparticipation in athletics)
      increased the likelihood of being a smoker. CONCLUSIONS: This study's findings
      have important implications for health education and promotion among college
      populations.

PMID- 9584014
TI  - HIV seroprevalence among street-recruited injection drug and crack cocaine users
      in 16 US municipalities.
AB  - OBJECTIVES: This study deter- mined human immunodeficiency virus (HIV)
      seroprevalence and factors associated with HIV infection among street-recruited
      injection drug users and crack cocaine smokers. METHODS: An analysis was
      performed on HIV serologies and risk behaviors of 6402 injection drug users and
      3383 crack smokers in 16 US municipalities in 1992 and 1993. RESULTS: HIV
      seroprevalence was 12.7% among injection drug users and 7.5% among crack smokers.
      Most high-seroprevalence municipalities (>25%) were located along the eastern
      seaboard of the United States. In high-seroprevalence municipalities, but not in
      others, HIV seroprevalence was higher for injection drug users than for crack
      smokers. Among injection drug users, cocaine injection, use of speedballs
      (cocaine or amphetamines with heroin), and sexual risk behaviors were
      independently associated with HIV infection. Among crack smokers, sexual risk
      behaviors were associated with HIV infection. CONCLUSIONS: Injection drug users
      and crack smokers are at high risk for HIV infection.

PMID- 9584015
TI  - Histories of substance use and risk behavior: precursors to HIV seroconversion in
      homosexual men.
AB  - OBJECTIVES: This study compared history of substance use and episodic use in
      terms of HIV seroconversion. METHODS: A sample of 337 baseline HIV-negative gay
      men was followed for 6 years. Bivariate and survival analyses were used to
      compare 39 converters with nonconverters on substance use behaviors. RESULTS:
      Seroconverters were consistently more likely to report use of marijuana, nitrite
      inhalants, amphetamines, and cocaine than nonconverters. Consistent use of
      nitrite inhalants and amphetamines increases the relative risk of seroconversion,
      while episodic use does not. Both patterns of cocaine use increase seroconversion
      risk. CONCLUSIONS: There are three potential mechanisms for an increased risk of
      conversion due to consistent substance use.

PMID- 9584016
TI  - National survey of the states: policies and practices regarding drug-using
      pregnant women.
AB  - OBJECTIVES: This study assessed the impact of national policy shifts on state
      policies and practices regarding substance-using mothers. METHODS: A 1995
      telephone survey of substance abuse and child protective services directors in
      all 50 states and the District of Columbia was compared with a similar 1992
      survey. RESULTS: There have been significant increases in state interventions for
      drug-using pregnant women (e.g., criminal prosecution, toxicology testing of
      women and neonates). Federal resources for treatment and oversight are being
      replaced by state control of reduced funds for treatment. CONCLUSIONS: The
      earlier policy of expanding treatment for addicted women is being replaced by
      reduction of services and increased state intervention.

PMID- 9584017
TI  - Beyond black box epidemiology.

PMID- 9584018
TI  - Nicotine concentration in the hair of nonsmoking mothers and size of offspring.
AB  - OBJECTIVES: The purpose of this study was to estimate the risk of small-for
      gestational-age birth by levels of nicotine in the hair of mothers and offspring.
      METHODS: In a sample of 58 case subjects and 105 control subjects, hair nicotine
      concentrations were measured by gas chromatography and mass spectrometry.
      RESULTS: With women whose hair nicotine concentrations were in the lowest
      quartile as the reference group, the odds ratio (OR) for small-for-gestational
      age birth was increased among women with concentrations in the upper and two
      middle quartiles (OR=4.2, 95% confidence interval [CI]=1.5, 11.5, and OR = 3.2,
      95% CI=1.3, 8.0). When smoking mothers were excluded from the analysis, the
      corresponding odds ratios were 2.1 (95% CI=0.4, 10.1) and 3.4 (95 % CI= 1.3,
      8.6). CONCLUSIONS: The results suggest that passive maternal smoking increases
      the risk of small-for-gestational-age births.

PMID- 9584019
TI  - Preventing scientific misconduct.

PMID- 9584020
TI  - Ethical dilemmas in polio eradication.

PMID- 9584021
TI  - Ethical dilemmas in polio eradication. Hyder responds.

PMID- 9584022
TI  - Means and ends: cost-effectiveness and overall costs.

PMID- 9584023
TI  - Persons with disabilities.

PMID- 9584024
TI  - Breast milk compounds.

PMID- 9584025
TI  - On nurses.

PMID- 9584026
TI  - Norplant coercion.

PMID- 9584027
TI  - Use and misuse of population attributable fractions.

PMID- 9584028
TI  - Incidence and predictors of smokeless tobacco use among US youth.
AB  - OBJECTIVES: The purpose of this study was to provide estimates of the cumulative
      incidence of initiation of smokeless tobacco use in a cohort of young persons and
      to explore sociodemographic, environmental, behavioral, and personal predictors
      of experimentation with and regular use of snuff or chewing tobacco. METHODS: The
      data for this cohort study were derived from the 1989 Teenage Attitudes and
      Practices Survey and its 1993 follow-up. The study included 7830 young people 11
      through 19 years of age at baseline. RESULTS: During the 4 years, 12.7% of
      participants (20.9% of male participants) first tried smokeless tobacco, and 4.0%
      (8.0% of male participants) became self-classified regular users. This suggests
      that, each year, approximately 824000 young people in the United States 11 to 19
      years of age experiment with smokeless tobacco and about 304 000 become regular
      users. Cumulative incidence was highest for male non-Hispanic Whites. Predictors
      of regular use included age, geographic region, cigarette smoking, participation
      in organized sports, and perceived friends' approval or indifference.
      CONCLUSIONS: Public health approaches to preventing use of smokeless tobacco
      should include development of skills for responding to pressures to use tobacco.

PMID- 9584029
TI  - Initiation of use of alcohol, cigarettes, marijuana, cocaine, and other
      substances in US birth cohorts since 1919.
AB  - OBJECTIVES: This study examined recent trends in initiation of psychoactive drug
      use. METHODS: Data from the 1991 through 1993 National Household Surveys on Drug
      Abuse were used to compare the percentages of US cohorts born from 1919 through
      1975 who began using drugs before the ages of 15, 21, and 35. RESULTS: Initiation
      of cigarette smoking by males peaked in the 1941-1945 cohort, then declined
      steadily. For females, early smoking initiation rose through the 1951-1955 cohort
      and then stabilized. Initiation of alcohol use was less common than smoking for
      pre1950 cohorts but increased steadily, approaching cigarette use for cohorts
      born in the early 1970s. Only 2% of teenagers born in 1930-1940 tried marijuana;
      half the teenagers born in 1956-1965 did so. The percentage initiating marijuana
      use declined in the 1980s, more so among young adults than among teenagers. The
      use of cocaine and other illicit drugs echoed the rise of marijuana use but
      peaked later and showed less evidence of subsequent decline. Sex differences
      declined over time for every drug. CONCLUSIONS: Cohorts born since World War II
      have had much higher rates of illicit drug use initiation, but trends have varied
      by drug type, possibly reflecting changes in relative prices.

PMID- 9584030
TI  - Retention, HIV risk, and illicit drug use during treatment: methadone dose and
      visit frequency.
AB  - OBJECTIVES: This study examined two major methadone treatment factors, visit
      frequency and methadone dose, posited to be important in reducing intravenous
      drug use and human immunodeficiency virus (HIV) transmission. METHODS: One
      hundred fifty opiate-dependent subjects randomly assigned to four groups received
      50 or 80 mg of methadone and attended a clinic 2 or 5 days per week. RESULTS:
      Survival analysis indicated higher dropout rates for groups having five vs two
      visits per week (Chi2[1]=7.76). Higher proportions of opiate-positive results on
      urine screens were associated with lower methadone doses (F[1,91]=4.74).
      CONCLUSIONS: Receiving take-home doses early in treatment enhanced treatment
      retention. The 50-mg dose combined with five visits per week produced the worst
      outcome. Fewer visits enhanced retention at 50 mg, but opiate use rates were
      higher at this dose than they were for either 80-mg group. The HIV infection rate
      at entry was 9%. No subjects seroconverted during the study. Risk behaviors for
      acquired immunodeficiency syndrome declined over time regardless of group/dose
      assignment. These results have important implications for modification of
      regulatory and clinic policy changes.

PMID- 9584031
TI  - Race and the risk of fatal injury at work.
AB  - OBJECTIVES: This study examined employment patterns of African-American and White
      workers and rates of unintentional fatal injuries, METHODS: Medical examiner and
      census data were used to compare occupational fatality rates for African
      Americans and Whites in North Carolina and to adjust for racial differences in
      employment patterns. RESULTS: African Americans' occupational fatality rate was
      higher by a factor of 1.3 to 1.5. Differences in employment structure appear to
      explain much of this disparity. However, the fatality rate for African-American
      men would have been elevated even if they had had the same employment patterns as
      White men. CONCLUSIONS: inequalities in access to the labor market, unequal
      distribution of risk within jobs, and explicit discrimination are all potential
      explanations for racial disparities in occupational injury mortality. These
      conditions can be addressed through a combination of social and workplace
      interventions, including efforts to improve conditions for the most disadvantaged
      workers.

PMID- 9584032
TI  - An evaluation of Safe Dates, an adolescent dating violence prevention program.
AB  - OBJECTIVES: This study assessed the effects of the Safe Dates program on the
      primary and secondary prevention of adolescent dating violence. METHODS: Fourteen
      schools were randomly allocated to treatment conditions. Eighty percent (n=1886)
      of the eighth and ninth graders in a rural county completed baseline
      questionnaires, and 1700 (90%) completed follow-up questionnaires. RESULTS:
      Treatment and control groups were comparable at baseline. In the full sample at
      follow-up, less psychological abuse, sexual violence, and violence perpetrated
      against the current dating partner were reported in treatment than in control
      schools. In a subsample of adolescents reporting no dating violence at baseline
      (a primary prevention subsample), there was less initiation of psychological
      abuse in treatment than in control schools. In a subsample of adolescents
      reporting dating violence at baseline (a secondary prevention subsample), there
      was less psychological abuse and sexual violence perpetration reported at follow
      up in treatment than in control schools. Most program effects were explained by
      changes in dating violence norms, gender stereotyping, and awareness of services.
      CONCLUSIONS: The Safe Dates program shows promise for preventing dating violence
      among adolescents.

PMID- 9584033
TI  - Obstetric care and payment source: do low-risk Medicaid women get less care?
AB  - OBJECTIVES: This study examined whether Medicaid-insured women at low risk
      receive less adequate obstetrical care than privately insured women. METHODS: Low
      risk women who were cared for by a random sample of obstetrical providers in
      Washington State were randomly selected. Information on all prenatal and
      intrapartum services was abstracted from medical records. Service information was
      aggregated into standardized resource-use units. Results compared Medicaid
      insured women with those who were privately insured. RESULTS: Medicaid-insured
      women were significantly younger (22.5 years vs 26.9 years) and averaged 6% fewer
      visits than privately insured women. Nonetheless, Medicaid status had no
      meaningful association with prenatal, intrapartum, or overall resource use. Some
      variation occurred in individual resources received. Medicaid-insured women had
      38.8% more resources expended on testing for sexually transmitted diseases.
      Privately insured women had more resources expended on alpha-fetoprotein testing
      and on amniocentesis. There were no meaningful differences in birthweight or
      gestational age at delivery. CONCLUSIONS: In this study of women who entered
      obstetrical care at low risk, similar care and resources were expended on
      Medicaid-insured and on privately insured women.

PMID- 9584034
TI  - The relationship between suicide risk and sexual orientation: results of a
      population-based study.
AB  - OBJECTIVES: This study examined the relationship between sexual orientation and
      suicide risk in a population-based sample of adolescents. METHODS: Participants
      were selected from a cross-sectional, statewide survey of junior and senior
      public high school students. All males (n = 212) and females (n = 182) who
      described themselves as bisexual/homosexual were compared with 336 gender-matched
      heterosexual respondents on three outcome measures: suicidal ideation, intent,
      and self-reported attempts. Logistic regression analyses were used to examine the
      association between sexual orientation and outcome measures with adjustment for
      demographic characteristics. RESULTS: Suicide attempts were reported by 28. 1 %
      of bisexual/homosexual males, 20.5% of bisexual/homosexual females, 14.5% of
      heterosexual females, and 4.2% of heterosexual males. For males, but not females,
      bisexual/homosexual orientation was associated with suicidal intent (odds ratio
      [OR] = 3.61 95% confidence interval [CI = 1.40, 9.36) and attempts (OR=7.10; 95%
      CI=3.05, 16.53). CONCLUSIONS: There is evidence of a strong association between
      suicide risk and bisexuality or homosexuality in males.

PMID- 9584035
TI  - A cost-benefit analysis of a cardiovascular disease prevention trial, using
      folate supplementation as an example.
AB  - OBJECTIVES: This study illustrates a cost-benefit analysis of clinical trial
      design, using as an example a trial of folate supplementation to prevent
      cardiovascular disease. METHODS: Bayesian statistical and decision-analytic
      techniques were used to estimate the cost-benefit and sample size of a placebo
      controlled trial of folate targeted to US citizens, aged 35 to 84 years, with
      elevated serum homocysteine levels. The main end point is event-free survival
      (i.e., survival without new ischemic heart disease or stroke) at 5 years.
      RESULTS: Because the screening cost and annual cost and inconvenience of taking
      folate is small compared with the consequences of stroke, ischemic heart disease,
      or death, the increase in 5-year event-free survival with folate that should
      compel the use of folate is just 1.1%. The sample size per group needed to
      establish this level of folate's medical effectiveness is estimated to be 17310.
      Such a trial would provide an expected societal cost-benefit savings exceeding
      $11 billion within 15 years. CONCLUSIONS: This study illustrates how Bayesian
      methods may help in assessing the societal cost-benefit consequences of proposed
      disease prevention trials, deciding which trials are worth sponsoring, and
      designing cost-effective trials.

PMID- 9584036
TI  - Two alternative job stress models and the risk of coronary heart disease.
AB  - OBJECTIVES: This study examined the association between two alternative job
      stress models-the effort-reward imbalance model and the job strain model-and the
      risk of coronary heart disease among male and female British civil servants.
      METHODS: The logistic regression analyses were based on a prospective cohort
      study (Whitehall II study) comprising 6895 men and 3413 women aged 35 to 55
      years. Baseline measures of both job stress models were related to new reports of
      coronary heart disease over a mean 5.3 years of follow-up. RESULTS: The imbalance
      between personal efforts (competitiveness, work-related overcommitment, and
      hostility) and rewards (poor promotion prospects and a blocked career') was
      associated with a 2.15-fold higher risk of new coronary heart disease. Job strain
      and high job demands were not related to coronary heart disease; however, low job
      control was strongly associated with new disease. The odds ratios for low job
      control were 2.38 and 1.56 for self-reported and externally assessed job control,
      respectively. Work characteristics were simultaneously adjusted and controlled
      for employment grade level, negative affectivity, and coronary risk factors.
      CONCLUSIONS: This is apparently the first report showing independent effects of
      components of two alternative job stress models-the effort-reward imbalance model
      and the job strain model (job control only)-on coronary heart disease.

PMID- 9584037
TI  - Perceived parental burden and service use for child and adolescent psychiatric
      disorders.
AB  - OBJECTIVES: Pediatric chronic physical illness and adult psychiatric disorders
      are substantial sources of burden for family care-takers, but little attention
      has been paid to parental burden resulting from children's or adolescents'
      psychiatric disorders. This paper describes the predictors of perceived parental
      burden and its impact on the use of specialty mental health and school services.
      METHODS: A representative general population sample of 1015 9-, 11-, and 13-year
      olds and their parents completed structured psychiatric diagnostic interviews and
      the Child and Adolescent Burden Assessment. RESULTS: Weighted estimates indicated
      that 10.7% of parents in the general population perceived burden resulting from
      their children's symptomatology. Significant predictors of perceived burden were
      levels of child symptomatology and impairment and parental mental health
      problems. Children's depressive and anxiety disorders were associated with less
      burden than other diagnoses. The effects of child disorder severity on specialty
      mental health service use appeared to be mediated by the level of burden induced.
      CONCLUSIONS: Substantial levels of parental burden resulted from child
      psychiatric disorders and were a major reason for specialist mental health
      service use.

PMID- 9584038
TI  - Fifteen-year follow-up of smoking prevention effects in the North Karelia youth
      project.
AB  - OBJECTIVES: This study evaluated the long-term effects of a school- and community
      based smoking prevention program in Finland. METHODS: Four intervention schools
      from North Karelia and two control schools from another province were chosen for
      the evaluation. Students who received the intervention were taught to resist
      social pressures to smoke. The program began in 1978 with seventh-grade students
      and ran through 1980, with a 15-year follow-up. In North Karelia, a community
      based smoking cessation program for adults was also carried out. RESULTS: Mean
      lifetime cigarette consumption was 22% lower among program subjects than among
      control subjects. Smoking and prevalence were lower up to the age of 21.
      CONCLUSIONS: Long-term smoking prevention effects can be achieved if a school
      based program using a social influence model is combined with community and mass
      media interventions.

PMID- 9584039
TI  - Intermittent smokers: a descriptive analysis of persons who have never smoked
      daily.
AB  - OBJECTIVES: This study assessed the prevalence of and demographic variables
      associated with lifetime never-daily smoking in the United States. METHODS:
      Descriptive demographic data and logistic regression analyses were used to
      examine associations with never-daily smoking. RESULTS: Lifetime never-daily
      smokers constituted a significant minority of non-White smokers. There was a
      strong association between never-daily smoking and college education among young
      adults, particularly men. Although never-daily smoking was associated with
      initiation behavior among young smokers, it also represented a persistent pattern
      for some smokers, particularly non-Whites and Hispanics. CONCLUSIONS: The
      demographic distribution of never-daily smoking may have implications for
      developing culturally appropriate smoking prevention and cessation strategies.

PMID- 9584040
TI  - At-risk drinking in an HMO primary care sample: prevalence and health policy
      implications.
AB  - OBJECTIVES: This study was designed to determine the prevalence of at-risk
      drinking using varying alcohol use criteria. METHODS: A period prevalence survey
      was conducted in 22 primary care practices (n = 19372 adults). RESULTS: The
      frequency of at-risk alcohol use varied from 7.5% (World Health Organization
      criteria) to 19.7% (National Institute on Alcohol Abuse and Alcoholism criteria).
      A stepwise logistic model using National Institute on Alcohol Abuse and
      Alcoholism criteria found male gender, current tobacco use, never married status,
      retirement, and unemployment to be significant predictors of at-risk alcohol use.
      CONCLUSIONS: Public health policy needs to move to a primary care paradigm
      focusing on identification and treatment of at-risk drinkers.

PMID- 9584041
TI  - Smoking cessation, weight gain, and changes in cardiovascular risk factors during
      menopause: the Healthy Women Study.
AB  - OBJECTIVES: The relationship between smoking cessation, subsequent weight gain,
      and cardiovascular disease risk factors from premenopause to postmenopause was
      studied. METHODS: Healthy Women Study participants were assessed for changes in
      coronary heart disease risk factors from a premenopausal baseline assessment to
      first- and second-year postmenopausal assessments. RESULTS: Although ex-smokers
      gained substantially more weight than nonsmokers and smokers, they did not
      experience a greater increase in cardiovascular risk factors. In fact, the
      results indicated a trend toward ex-smokers' high-density lipoprotein cholesterol
      levels increasing slightly more than those of nonsmokers and smokers.
      CONCLUSIONS: Smoking cessation in perimenopausal to postmenopausal women is
      associated with greater weight gain but appears to be modestly associated with
      certain positive changes in cardiovascular risk factors.

PMID- 9584043
TI  - European Mathematical Genetics Meeting. Munich, Germany, 5-7 April 1997.
      Abstracts.

PMID- 9584042
TI  - Risk of assaultive violence and alcohol availability in New Jersey.
AB  - OBJECTIVES: This study examined the relationship between rate of assaultive
      violence and density of alcohol outlets in New Jersey. METHODS: Data pertaining
      to assaultive violence, alcohol outlet density, and sociodemographic factors were
      obtained from municipalities in New Jersey (n = 223) and assessed through
      bivariate and multivariate analyses. RESULTS: Sociodemographic factors accounted
      for 70% (R(2)=.70) of the variance in the rate of assaultive violence. Outlet
      density did not add significantly to the explained variance of this model.
      CONCLUSIONS: In New Jersey, alcohol outlet density is not geographically
      associated with higher rates of violence. Alternative methodological and analytic
      techniques are required to better specify the relationship between alcohol
      availability and violence.

PMID- 9584044
TI  - Tamoxifen associated uterine pathology in breast cancer patients with abnormal
      bleeding.
AB  - The purpose of this study was to evaluate the underlying pathology in breast
      cancer patients treated with tamoxifen who present with abnormal bleeding. A
      total of 56 cases were studied and the histopathologic features of 50 curettage
      and 18 laparotomy specimens were reviewed. All patients were under tamoxifen
      treatment (10-40 mg daily) for a period ranging from 5 months to 15 years.
      Cervical and endometrial polyps were the most common finding in the D and C
      material (44%). Hyperplasia was the most frequent feature identified at
      hysterectomy, often combined with leiomyomas, adenomyosis and ovarian tumors.
      Five primary adenocarcinomas of the endometrium, most of them Stage I beta, Grade
      I minimally invading, were found as well. These data support the hypothesis that
      tamoxifen exerts a proliferative estrogen-like effect on the uterus. Abnormal
      bleeding in women under TAM treatment warrants prompt investigation and careful
      follow up of the patients.

PMID- 9584046
TI  - Expression of keratin 13, 14 and 19 in oral hyperplastic and dysplastic lesions
      from Sudanese and Swedish snuff-dippers: association with human papillomavirus
      infection.
AB  - Changes in the expression of keratins (Ks), indicating disturbed tissue
      differentiation, is one possible marker of malignant potential in stratified
      squamous epithelia. The presence of human papillomaviruses (HPVs) in the
      epithelium of the uterine cervix is increasingly regarded as a marker of risk for
      cervical cancer: However, a similar role in oral cancer and precancer remains
      controversial. To address these questions, potentially malignant oral mucosal
      lesions from Sudanese (9 hyperplasias/40 dysplasias) and Swedish (15
      hyperplasias) snuff-dippers were examined by immunohistochemistry for expression
      of K types 13, 14 and 19 using monoclonal antibodies directed against each. HPV
      infection was searched for by in situ hybridization (ISH) using the cocktail HPV
      OmniProbe and the ViraType probe. For the Sudanese lesions, moderate to intense
      expression of both K13 (basal, basal/intermediate, basal/intermediate/superficial
      and intermediate/superficial cell layers) and K14 (basal, basal/intermediate cell
      layers) was found in 49/49 (100%). For the Swedish lesions, weak to moderate
      expression of K13 (basal, basal/intermediate cell layers) was found in 12/15
      (80%) and 10/15 (67%), respectively. In the Sudanese lesions, expression of K13
      showed a distinct pattern through the oral mucosa and its verrucous projections,
      with an increase towards the superficial cell layers of dysplastic, but not
      hyperplastic epithelium. K19 was expressed in the basal cell layer in 16/49 (33%)
      of the Sudanese lesions, while all the Swedish lesions were negative. HPV was
      found in only 2 Sudanese cases, both of which harboured both type 6 and type 11:
      both these cases demonstrated mild epithelial dysplasia, The present study shows
      that a) there is a high prevalence of expression of both K13 and K14 in oral
      lesions from Sudanese toombak dippers indicating dysregulation of keratinocyte
      maturation b) one-third of the Sudanese oral lesions expressed K19, regarded as a
      basal keratin representing epithelial dedifferentiation, which may prove to be a
      valuable risk marker in follow-up studies c) HPV genome is found infrequently in
      oral lesions from Sudanese toombak-dippers, suggesting that these viruses may not
      play a prominent role in the early stages of carcinogenesis in these subjects.
      These markers were less often expressed in the Swedish lesions, consistent with
      their much lower rate of malignant transformation.

PMID- 9584045
TI  - Tumor markers in response monitoring and prognosis of non-small cell lung cancer:
      preliminary report.
AB  - BACKGROUND: The significance of tumor markers in lung cancer is not well
      established. PATIENTS AND METHODS: We analyzed level of serum markers as
      prognostic factor of response and survival in 46 evaluable patients with locally
      advanced or metastasic non small cell lung cancer. All patients were treated with
      cisplatin 120 mg/m2 or carboplatin 400 mg/m2 day 1, plus etoposide 80 mg/m2 days
      1 to 3. RESULTS: Partial response was obtained in 11 patients (24%),
      stabilization in 18 and progression in 17. Tumor marker sensitivities were: CEA
      37%, CA 125 54.5%, SCC 17.5%, NSE 30.5%, and CYFRA 52%. Higher levels of CEA and
      NSE correlated with more probability of response (p < 0.001 and p = 0.002). The
      survival probability of patients with normal pretreatment levels of NSE was
      significantly better than those with NSE over normal level (15.2 vs 7.2 months) p
      = 0.02. In patients who achieved partial response, CEA, CA 125 and CYFRA levels
      decreased significantly with respect to the pretreatment values. CONCLUSIONS:
      Patients with high CEA and NSE serum level have an increased probability of
      response than patients with low initial levels; however, patients with high
      initial level of NSE have poor survival. The decrease in CEA, CA 125 and CYFRA
      values at the moment of response evaluation could help in response assessment.

PMID- 9584047
TI  - Prediction of survival in breast cancer: evaluation of different multivariate
      models.
AB  - BACKGROUND: We compared the performance of multivariate models based on mitotic
      activity index, lymph node status, and tumor size in the prognostication of
      breast cancer. MATERIAL AND METHODS: Cox and discriminant models for survival
      were created for two patient groups: a) 120 breast cancer patients, and b) 86
      patients with ductal infiltrating carcinoma. The models were compared with the
      model of Baak et al (1985). RESULTS: The models distinguished between dying and
      surviving patients with an efficiency of 70.9-77.9% in mutual tests. With a
      single cutoff the model of Baak et al was less efficient (50.8-65.8%). If a
      region of uncertainty was allowed between two cutpoints, the efficiencies below
      and above the cutpoints increased. When the uncertain region included a third of
      the patients, the efficiency varied between 73.8 and 84.7%. CONCLUSION:
      Multivariate models seem to need a region of uncertainty between two
      discriminating cutpoints. These models resulted in the correct prediction of
      prognosis in about 75% and more of patients. With different materials the models
      differed in efficiency. With a region of uncertainty the model of Baak et al
      performed well with completely independent material.

PMID- 9584048
TI  - Ethnic or environmental differences in disparate geographic regions may influence
      the histology of flat colorectal neoplasias.
AB  - Histologic sections of endoscopically flat colorectal polyps removed in Tokyo and
      Stockholm were reviewed. A total of 178 flat colorectal neoplasias (88 from the
      Tokyo Medical College Hospital, Tokyo and 90 from the Karolinska Hospital,
      Stockholm) were classified following strict histologic criteria by two different
      pathologists (one Swedish and the other Japanese). The number of polyps with high
      grade dysplasia, with intramucosal carcinoma and with invasive carcinoma were
      significantly higher (p < 0.001) in Tokyo (61.4% or 54/88) than in Stockholm
      (15.0% or 14/90). The present results suggest that flat colorectal neoplasic
      polyps may be histologically more "severe" and more "aggressive" in Japanese than
      in Swedish patients. The possibility that more "advanced" lesions had been
      inadvertently removed in Tokyo was discounted as Japanese endoscopists were also
      instrumental in excising many of the flat colorectal polyps in Stockholm. Ethnic
      and/or environmental differences seem to play a crucial role in the evolution of
      flat colorectal neoplasic polyps from LGD and HGD, to intramucosal and to
      invasive carcinoma.

PMID- 9584049
TI  - Caffeine-assisted chemotherapy and minimized tumor excision for nonmetastatic
      osteosarcoma.
AB  - Osteosarcoma is usually treated with intensive preoperative and postoperative
      chemotherapy and wide tumor resection, resulting in a 60% to 70% 5-year survival
      rate. Caffeine has a DNA-repair inhibiting effect. We therefore investigated the
      impact of caffeine given in conjunction with chemotherapy and limb-sparing
      surgery on survival and local tumor control in patients with nonmetastatic, high
      grade osteosarcoma. Twenty-two patients were given 3 to 5 preoperative courses of
      intra-arterial cisplatin (120 mg/m2, 1 to 2 hours) and caffeine (1.5 g/m2/day x 3
      days) with or without doxorubicin (30 mg/m2/day x 2 days). Following this
      treatment, limb-sparing surgery was performed by means of intentional marginal
      excision aiming at preservation of important structures such as major
      neurovascular bundles, tendons, ligaments and the epiphysis. Three courses of
      cisplatin and doxorubicin combined with caffeine, and high-dose methotrexate with
      vincristine and citrovorum factor rescue were given intravenously as
      postoperative chemotherapy for 21 patients and three courses of high-dose
      methotrexate and combination of ifosfamide, etoposide and methotrexate for 1
      patient. Following the preoperative chemotherapy, there were no viable tumor
      cells in 19 patients, only scattered foci of viable cells in 2 patients, and some
      areas of viable tumor cells in 1. The 21 patients with a good chemotherapeutic
      response on radiographs underwent minimized marginal excision. Functional
      evaluation of the affected limbs was excellent for 17 patients, good for 3, fair
      for 1, and poor for 1. No local tumor recurrence was seen in this series.
      Eighteen patients remain disease-free with a mean follow-up of 61 months. Two
      patients died of metastatic disease, 1 died of chemotherapy-related
      complications, and 1 died of unknown causes. The overall 5-year cumulative
      survival rate was 90%, and the 5-year event-free survival rate was 75%.
      Chemotherapeutic caffeine enhanced tumor necrosis and improved the success rate
      of limb-sparing surgery using marginal procedure without any adverse impact on
      survival. The results of our limited clinical trial appear to justify further
      prospective, multicenter randomized trials of the benefits of caffeine combined
      with chemotherapy for nonmetastatic osteosarcoma and other malignant neoplasms.

PMID- 9584050
TI  - Histopathologic findings in thickened endometria, as measured by ultrasound in
      asymptomatic, postmenopausal breast cancer patients on various adjuvant treatment
      including tamoxifen.
AB  - Pallents with breast cancer exhibit an increased risk of developing cancer from
      other organs, a risk that might increase due to tamoxifen treatment. This drug
      has been found to cause activation of oestrogen receptors, leading to oestrogenic
      effects on the postmenopausal endometrium. We report follow-up of 94 patients
      with breast cancer without initial symptoms aged more than 50 years at the time
      of operation. They were followed-up with vaginal ultrasound at regular intervals
      and endometrial sampling was performed according to treatment after surgery:
      tamoxifen, tamoxifen in combination with other regimes and without tamoxifen
      treatment. A large proportion were investigated prior to treatment. We identified
      endometrial carcinoma, metastasis of breast carcinoma and histopathological
      changes in 17/67 (25%) of the patients treated with tamoxifen compared to 1/32 in
      those not treated with tamoxifen.

PMID- 9584051
TI  - Proliferating cell nuclear antigen (PCNA) as a prognostic factor in renal cell
      carcinoma.
AB  - BACKGROUND: A retrospective study was performed on patients with renal cell
      carcinoma to determine whether tumoral proliferating cell nuclear antigen (PCNA)
      is a predictive factor. METHODS: We studied immunohisto-chemical PCNA expression
      with pc10 monoclonal antibody in 109 renal tumor paraffin sections. These tumors
      were previously classified according to cellular type by Thoenes, Furman's
      grading and Robson's staging, Moreover, we counted the number of mitoses in 10
      high power fields (HPF) and also evaluated the tumoral necrosis percentage. Ten
      year survival curve of Kaplan and Meier was obtained for 90 patients. RESULTS:
      Nuclear immunostaining for PCNA showed a statistical correlation with Robson's
      stage, cellular type and nuclear grade. Moreover, the number of positive nuclei
      was higher in tumors presenting an elevated mitosis count and higher in degree of
      necrosis. Survival was significantly poorer in patients whose PCNA index was
      greater than 5%. Nuclear PCNA immunostaining was shown to be an independent
      prognostic factor in patients with Robson stage I and also in those who had high
      cytological grading. CONCLUSIONS: These results show PCNA to be a prognostic
      marker for RCC.

PMID- 9584052
TI  - Correlation of prostate specific antigen immunoactivity (IR-PSA) to other
      prognostic factors in female breast cancer.
AB  - Recently, using an ultrasensitive time-resolved immuno-fluorometric assay, PSA
      immunoreactivity (IR-PSA) was found in breast tumor cytosols. We retrospectively
      studied 219 breast cancer patients, measuring IR-PSA in the tumor cytosols, and
      classified the breast cancers as either PSA positive or PSA negative based on an
      IR-PSA cut off level of 1 pg/mg. Multivariated analysis showed that IR-PSA is an
      independent favourable prognostic indicator for postmenopausal, node positive
      breast cancer patients. Additionally, IR-PSA correlates with reduced risk of
      relapse in ER+ve tumors and is negatively correlated with mutated p53, which
      increases the risk of relapse.

PMID- 9584053
TI  - Histopathologic prognostic score in colorectal adenocarcinomas.
AB  - OBJECTIVE: To analyze the prognostic value of a set of pathological variables
      after curative resection for large bowel adenocarcinoma and to test a prognostic
      score derived from factors with independent effect. PATIENTS AND METHODS: The
      study is based on data from 292 consecutive unselected patients (B-C Astler
      Coller stages). Histopathological features were evaluated prospectively on the
      resected primary tumors. Relationship between these factors and risk of
      recurrence was assessed by a Cox's proportional regression analysis. RESULTS:
      Four variables retained independent prognostic significance: extent of bowel wall
      invasion, peritumoral lymphocytic infiltration, number of positive nodes and
      vascular invasion. A prognostic score based on the regression coefficients
      attained by such variables was developed. This system revealed four prognostic
      groups. Group I included 14% of patients, with 94% 5-year disease-free survival.
      These figures were: 35% and 60% in group II; 43% and 46% in group III; and 7% and
      24.4% in group IV. Histopathologic score applied to bearers of Astler-Coller B2
      tumors permitted the identification of two populations, one characterized by a
      low risk of relapse and another with high risk (p = 0.002). CONCLUSION: A
      prognostic score based in the evaluation of four histopathologic parameters
      concerning the tumor phenotype enables the identification of groups of patients
      at risk of relapse after curative resection for colorectal adenocarcinoma.

PMID- 9584054
TI  - Microbial photodegradation of aminoarenes. Metabolism of 2-amino-4-nitrophenol by
      Rhodobacter capsulatus.
AB  - The phototrophic bacterium Rhodobacter capsulatus photoreduces 2,4-dinitrophenol
      to 2-amino-4-nitrophenol, which is further metabolized by an aerobic pathway that
      is also light-dependent. The catabolism of 2-amino-4-nitrophenol requires O2 and
      the presence of alternative carbon (C) and nitrogen (N) sources, preferably
      acetate and ammonium. Rhodobacter capsulatus B10, a bacterium unable to
      assimilate nitrate, releases negligible amounts of nitrite when growing with 2
      amino-4-nitrophenol, thus suggesting that an oxygenase, nitrite-producing
      activity is not involved in the metabolization of the compound. The diazotrophic
      growth of R. capsulatus increases in the presence of 2-amino-4-nitrophenol, but
      growth with ammonium is clearly inhibited by the compound. Mutant strains of R.
      capsulatus B10, which are affected in nifHDK, nifR1, or nifR4 genes, unable to
      fix dinitrogen, do not grow with 2-amino-4-nitrophenol as the sole N source. This
      indicates that the compound cannot be used as a N source. The nif mutants degrade
      2-amino-4-nitrophenol to the same extent as the wild-type in the presence of
      ammonium. The compound is not used as a C source by the bacterium, either.
      Aromatic stable intermediates, such as 2,4-diaminophenol or 4-nitrocatechol, are
      not detectable in microaerobic cultures of R. capsulatus growing with 2,4
      dinitrophenol or 2-amino-4-nitrophenol.

PMID- 9584055
TI  - A serological survey of the prevalence of Toxoplasma gondii in slaughtered
      animals in Saudi Arabia.

PMID- 9584056
TI  - Toxoplasmosis in goats in Cordoba, Spain: a seroepidemiological study.

PMID- 9584057
TI  - Antivenom reactions and complement depletion in snake bite.

PMID- 9584059
TI  - Is there a link between protein pICln and volume-regulated anion channels?

PMID- 9584058
TI  - Fatality following use of a tourniquet after viper bite envenoming.

PMID- 9584061
TI  - LETTERS

PMID- 9584060
TI  - Complete C-terminal sequence and genomic organization of MUC5B?

PMID- 9584062
TI  - ABSTRACTS: ANNUAL MEETING OF THE SOCIETY FOR THE STUDY OF INGESTIVE BEHAVIOR

PMID- 9584063
TI  - VOLUME CONTENTS AND INDEX

PMID- 9584064
TI  - The list heuristic for studying personality correlates of food choice behaviour:
      a review and results from two samples.
AB  - Over the past half century, a methodology has been used to investigate predictors
      of eating behaviour which involves the use of a list of foods, with subjects
      answering some preference question(s) about each food. For each person, the
      number of foods which elicit a particular response, usually of rejection, is used
      as a psychometric measure of their eating behaviour. We refer to this as the list
      heuristic. There has been great variability in the exact design used and
      comparing across studies is difficult. We tackle this issue by comparing
      "sublists" within one study. Previous list heuristic studies have found a link
      between behaviour and both anxiety and sensation seeking. Food choice behaviours
      can also be studied through psychometric questionnaires of more traditional
      design. Such studies have produced similar results and suggest a distinction
      between neophobia and general "pickiness". The list heuristic is used here in two
      studies. Our results are notably different, finding no relationships with anxiety
      and only weak relationships with sensation seeking. Further, results concerning
      food neophobia measures (list heuristic and questionnaire) suggest problems in
      differentiating food neophobia from more general food rejection behavior.

PMID- 9584065
TI  - Correlates of human food neophobia.

PMID- 9584066
TI  - LETTER

PMID- 9584067
TI  - ANNOUNCEMENT
AB  - Copyright

PMID- 9584068
TI  - Young children's difficulty acknowledging false belief: realism and deception.
AB  - This study was designed to help clarify some of the circumstances under which
      young children find it easier to acknowledge a false belief held by another
      person. In Experiment 1, preschoolers (mean age, 3 years; 11 months) watched a
      movie in which Ness had previously opened a familiar box in Jon's absence to
      reveal the stereotypical content, which she proceeded to replace with an atypical
      item. In a second movie, the box was seen to house an atypical content all along.
      Half the children watched Ness play the script in a neutral manner, while the
      rest watched her play it in a deceptive manner. There was a highly significant
      improvement in acknowledging Jon's false belief when children saw the
      stereotypical content of the box preliminary to its exchange for something
      atypical. In contrast, children gained no benefit from the way Ness played the
      script. The effect was replicated in a second experiment in which children were
      involved directly in the task. We conclude that presenting a physical
      instantiation of a false belief helps children to a small but reliable extent to
      correctly report that belief.

PMID- 9584069
TI  - Area judgment from width and height information: the case of the rectangle.
AB  - We assessed the effect on performance of shifting from a perceptual area judgment
      situation, in which the physical quantity to be judged (the area) is present in
      the stimulus, to a situation in which it is not present in the stimulus. Adults,
      9-year-olds, and 5-year-olds were shown combinations of horizontal and vertical
      lines of various sizes, presented on the same wall or on different walls, and
      asked to estimate the corresponding area. The following main results were
      obtained (a) When width and height information items were completely separated, 5
      and 9-year-old children gave the same weight to both dimensions in their
      estimations; (b) when width and height information items were on two different
      walls, adults gave a greater weight to the larger dimension; (c) when width and
      height were joined, 9-year-old children gave a greater weight to the larger
      dimension but when they were separated, they did not.

PMID- 9584070
TI  - Age-related differences in the preparatory processes of motor programming.
AB  - This article investigates the mechanisms underlying the age-related differences
      in information processing in the production of motor responses, especially the
      development of feedforward mechanisms. No age-related differences have emerged
      from developmental studies aiming at analyzing motor programming. Nevertheless,
      age effects have seldom been studied in function of motor preparation. The aim of
      the present experiment was (1) to study age differences in motor preparation, and
      (2) to validate the early maturation of movement parameters specification. Two
      conditions were used (1) no advanced information on the movement to be made was
      given to the subject (neutral prime), and (2) advanced information on which
      direction should be followed was provided to the subject, allowing him to prepare
      a response based on a prime (primed condition). Four age groups were studied 6,
      8, 10 and 22 years. Our results showed mainly an early maturation of the
      programming processes. More specifically, (1) beyond 6 years of age, children are
      capable of using the information provided by the prime to prepare their movement
      in advance, (2) costs and benefits of pre-programming do not vary significantly
      with age, (3) deprogramming-reprogramming of effector and direction is quite
      similar across the four age groups.

PMID- 9584071
TI  - Linguistic Relativity: The Case of Place Value in Multi-Digit Numbers
AB  - Differences between languages have been implicated recently in explanations of
      the cross-cultural disparities observed in children's mathematical performance on
      place value tasks (e.g., Miura, Okamaoto, Kim, Chang, Steere & Fayol, 1994).
      Children's understanding of place value was investigated here with 93 English
      speaking children and 50 Japanese-speaking children (aged 6 and 7 years). Cubes
      denoting units and tens were made available to children for producing
      representations of multi-digit numerals. It was found that subtle shifts in task
      instructions produced a marked influence on children's performance. In
      particular, differences between English and Japanese participants disappeared
      when the use of tens cubes was demonstrated in practice trials. More generally,
      the findings indicate that the influence of language on the cognitive
      representation of number is less direct than has previously been suggested.
      Copyright 1998 Academic Press.

PMID- 9584072
TI  - An Analytical Model for Flower Production in an Environment Where Resource
      Availability is Unpredictable
AB  - No abstract

PMID- 9584073
TI  - Comparison of the large subunit ribosomal DNA of Neospora and toxoplasma and
      development of a new genetic marker for their differentiation based on the D2
      domain.
AB  - The latest release of the large subunit ribosomal database contains 429
      sequences, yet only 10 (six nuclear and four mitochondrial) are derived from
      parasites of the phylum Apicomplexa. Three of these (all Toxoplasma gondii) were
      previously contained in the 1994 release of the database. As an initiative
      towards an understanding of ribosomal gene organization in the Apicomplexa, the
      primary sequence of the large subunit (LSU) rDNA of Neospora caninum is
      presented, and compared with a consensus sequence derived for the LSU rDNA of T.
      gondii. Nucleotide differences observed between these two taxa in the D2
      expansion segment (or domain) (also called the C1/C1' region) of the LSU rDNA
      were incorporated into a primer that forms the basis of a species-specific
      polymerase chain reaction (PCR) for N. caninum. The D2 domain of the LSU rDNA,
      therefore, represents a new genetic marker that can be used for the
      differentiation and identification of Neospora from other cyst-forming coccidia.

PMID- 9584074
TI  - Quantification of G protein mRNA using reverse transcription and competitive PCR
      with a colorimetric microplate assay.
AB  - This paper reports an assay for the quantification of levels of specific mRNA for
      the alpha subunits of the inhibitory G proteins G alpha i-1, G alpha i-2, and G
      alpha i-3. The assay employs reverse transcription and competitive polymerase
      chain reaction (PCR) coupled to enzyme-linked oligonucleotide sorbent assay for
      differential detection and quantification of PCR products. The assay was
      conducted with conventional thermal block PCR cyclers as well as rapid air
      microcapillary cyclers. The detection stage consists of three steps using
      synthetic oligonucleotides, commercially available reagents and a conventional 96
      well plate absorbance reader at settings of 450 and 630 nm. The assay is: (1)
      rapid, requiring about 3 h for quantification of PCR products; (2) safe, being
      non-radiometric; (3) relatively simple; (4) highly sensitive, being capable of
      detecting less than 10 initial copies of target cDNA; (5) precise, resolving two
      fold differences in initial copy numbers of specific sequences as low as 10(-20)
      mol; (6) linear over a 3 log range, with two-fold differences in the quantity of
      cDNA producing consistent reductions in quantity of specific cDNA detected; and
      (7) reproducible, intra-assay and inter-assay coefficients of variation being
      11.9 and 14.7%, respectively.

PMID- 9584075
TI  - PCR-SSCP of rDNA for the identification of Trichinella isolates from mainland
      china.
AB  - A polymerase chain reaction (PCR)-based single strand conformation polymorphism
      (SSCP) analysis of the expansion segment 5 (domain IV) of the large subunit of
      ribosomal DNA was employed to characterize seven isolates of Trichinella from
      China (A-G), including six of pig origin from regions in Dengxian (A), Tianjin
      (B), Harbin (D), Baoshan (E), Xinye (F) and Xian (G), and one of canine origin
      from Changchun (C). Isolates A, D, E, F and G were classified as Trichinella
      spiralis based on SSCP patterns, while the patterns for isolates B and C were
      consistent with those of Trichinella nativa or Trichinella T6. The results were
      supported by random amplified polymorphic DNA (RAPD) analysis using five decamer
      primers and were in accordance with ecological information for the isolates.
      Single strand conformation polymorphism results also allowed the direct display
      of mutational sequence variation in the expansion segment among the five isolates
      of T. spiralis from China, indicating its usefulness for studying population
      variation within that species.

PMID- 9584076
TI  - Small deletions in the regulatory 3' UTR of the human alpha-tropomyosin gene
      identified by differential display.
AB  - The differential display technique (DDT) was used to compare Fanconi anaemia (FA)
      fibroblasts with those of normal controls in a screen for genes involved in DNA
      repair, recognizing and handling damage or indicating cell cycle abnormalities as
      a result of genetic changes. The DDT revealed two different deletions of 5 and 11
      bp at a single locus in the 3' untranslated region (UTR) of a gene known to
      encode human alpha-tropomyosin (TPM1) in FA cells. These small deletions were
      detected by analysis of shifted 900-bp long cDNA fragments on polyacrylamide
      gels. They were characterized as loss of GTTTT or TGTTTTGTTTT, respectively, in a
      region with five GTTTT tandem repeats. Since it was postulated that the 3' UTR of
      the TPM1 gene plays a regulatory role in cell differentiation and tumour
      suppression, the existence and possible patterns of deletions in a variety of
      normal donors was investigated. The heterogenous distribution of non-deleted, 5-
      and 11-bp deleted 3' UTR regions indicate a polymorphism of the TPM1 gene in this
      tandem repeat motif. Therefore the expression pattern of these mutations among FA
      and non-FA cells rendered any direct relationship to the putative DNA repair
      defect in FA unlikely. Of note, however, the fact remains that such deletions
      reportedly facilitate mRNA degradation and may bear significance in the TPM1 gene
      action. Finally, of further interest is the finding that even small deletions can
      be identified by DDT in addition to the identification of the differential
      expression patterns of genes.

PMID- 9584077
TI  - Simple, reliable detection of T cell clones by PCR-LIS-SSCP analysis of TCRgamma
      rearrangement.
AB  - Clonal populations of T cells can be identified by polymerase chain reaction
      (PCR) amplification of the rearranged T cell receptor gamma (TCRG) chain gene.
      However, because of the limited combinatorial diversity of this locus it is
      necessary to separate the PCR product on the basis of sequence as well as size to
      distinguish clonal and polyclonal T cell populations. A simple method is
      described which achieves this by analysing the PCR product on a single-stranded
      conformation polymorphism (SSCP) gel. Sensitivity has been improved by denaturing
      the DNA using a low ionic strength (LIS) method rather than the more conventional
      alkali or formamide. Results from the PCR-LIS-SSCP method on a wide range of
      disorders and types of tissue samples show that clonality could be demonstrated
      in 40/44 cases.

PMID- 9584078
TI  - Limited allelic polymorphism in the human interleukin-3 gene.
AB  - Interleukin-3 (IL-3) is a cytokine expressed primarily in activated T cells mast
      cells and natural killer (NK) cells. Interleukin-3 has the capability to
      stimulate the proliferation and differentiation of multipotential stem cells and
      has a role in shaping the immune response. In order to better understand the
      biological role of IL-3, a study of polymorphisms within the human IL-3 gene and
      its upstream regulatory elements has been conducted. Using a modification of the
      bidirectional dideoxy fingerprinting method, a group of 88 Caucasoid individuals
      were screened for polymorphism in the IL-3 enhancer, promoter and gene coding
      regions. Analysis revealed the presence of several infrequent polymorphisms which
      may affect IL-3 functionality.

PMID- 9584079
TI  - A PAX3 polymorphism (T315K) in a family exhibiting Waardenburg Syndrome type 2.
AB  - Waardenburg Syndrome (WS) is an autosomal-dominant disorder phenotypically
      characterized by sensorineural hearing loss and pigmentary disturbances. Presence
      of dystopia canthorum is indicative of WS type 1 and results from defects in the
      PAX3 gene, whereas normally located medial canthi is characteristic of type 2 WS
      (WS2) and is associated with defects in the microphthalmia-associated
      transcription factor (MIFT) gene. Here a neutral polymorphism is reported in the
      PAX3 gene (T315K) in a family with WS2.

PMID- 9584080
TI  - Human papillomavirus type 33 DNA and E6-E7 transcripts in late passages of the UT
      DEC-1 vaginal keratinocyte cell line.
AB  - Transcription of human papillomavirus (HPV) type 33 early region was analysed in
      the UT-DEC-1 keratinocyte cell line, which has been derived from a HPV-33
      containing mild vaginal dysplasia. Fifteen cDNA clones from transcripts from the
      E6-E7 open reading frames were constructed and analysed. Most clones represented
      viral transcripts spliced within the E6 open reading frame, probably encoding the
      E7 protein. Interestingly, a less abundant unspliced transcript species with
      coding capacity for the full length E6 protein was found, reported here for the
      first time for the malignancy-associated HPV type 33.

PMID- 9584081
TI  - Hershey.

PMID- 9584082
TI  - Single-strand DNA-specific exonucleases in Escherichia coli. Roles in repair and
      mutation avoidance.
AB  - Mutations in the genes encoding single-strand DNA-specific exonucleases (ssExos)
      of Escherichia coli were examined for effects on mutation avoidance, UV repair,
      and conjugational recombination. Our results indicate complex and partially
      redundant roles for ssExos in these processes. Although biochemical experiments
      have implicated RecJ exonuclease, Exonuclease I (ExoI), and Exonuclease VII
      (ExoVII) in the methyl-directed mismatch repair pathway, the RecJ- ExoI- ExoVII-
      mutant did not exhibit a mutator phenotype in several assays for base
      substitution mutations. If these exonucleases do participate in mismatch
      excision, other exonucleases in E. coli can compensate for their loss. Frameshift
      mutations, however, were stimulated in the RecJ- ExoI- ExoVII- mutant. For
      acridine-induced frameshifts, this mutator effect was due to a synergistic effect
      of ExoI- and ExoVII- mutations, implicating both ExoI and ExoVII in avoidance of
      frameshift mutations. Although no single exonuclease mutant was especially
      sensitive to UV irradiation, the RecJ- ExoVII- double mutant was extremely
      sensitive. The addition of an ExoI- mutation augmented this sensitivity,
      suggesting that all three exonucleases play partially redundant roles in DNA
      repair. The ability to inherit genetic markers by conjugation was reduced
      modestly in the ExoI- RecJ- mutant, implying that the function of either ExoI or
      RecJ exonucleases enhances RecBCD-dependent homologous recombination.

PMID- 9584083
TI  - Spectra of spontaneous frameshift mutations at the hisD3052 allele of Salmonella
      typhimurium in four DNA repair backgrounds.
AB  - To characterize the hisD3052 -1 frameshift allele of Salmonella typhimurium, we
      analyzed approximately 6000 spontaneous revertants (rev) for a 2-base deletion
      hotspot within the sequence (CG)4, and we sequenced approximately 500 nonhotspot
      rev. The reversion target is a minimum of 76 bases (nucleotides 843-918) that
      code for amino acids within a nonconserved region of the histidinol dehydrogenase
      protein. Only 0.4-3.9% were true rev. Of the following classes, 182 unique second
      site mutations were identified: hotspot, complex frameshifts requiring DeltauvrB
      + pKM101 (TA98-specific) or not (concerted), 1-base insertions, duplications, and
      nonhotspot deletions. The percentages of hotspot mutations were 13.8% in TA1978
      (wild type), 24.5% in UTH8413 (pKM101), 31.6% in TA1538 (DeltauvrB), and 41.0% in
      TA98 (DeltauvrB, pKM101). The DeltauvrB allele decreased by three times the
      mutant frequency (MF, rev/10(8) survivors) of duplications and increased by about
      two times the MF of deletions. Separately, the DeltauvrB allele or pKM101 plasmid
      increased by two to three times the MF of hotspot mutations; combined, they
      increased this MF by five times. The percentage of 1-base insertions was not
      influenced by either DeltauvrB or pKM101. Hotspot deletions and TA98-specific
      complex frameshifts are inducible by some mutagens; concerted complex frameshifts
      and 1-base insertions are not; and there is little evidence for mutagen-induced
      duplications and nonhotspot deletions. Except for the base substitutions in TA98
      specific complex frameshifts, all spontaneous mutations of the hisD3052 allele
      are likely templated. The mechanisms may involve (1) the potential of direct and
      inverted repeats to undergo slippage and misalignment and to form quasi
      palindromes and (2) the interaction of these sequences with DNA replication and
      repair proteins.

PMID- 9584084
TI  - How optimized is the translational machinery in Escherichia coli, Salmonella
      typhimurium and Saccharomyces cerevisiae?
AB  - The optimization of the translational machinery in cells requires the mutual
      adaptation of codon usage and tRNA concentration, and the adaptation of tRNA
      concentration to amino acid usage. Two predictions were derived based on a simple
      deterministic model of translation which assumes that elongation of the peptide
      chain is rate-limiting. The highest translational efficiency is achieved when the
      codon recognized by the most abundant tRNA reaches the maximum frequency. For
      each codon family, the tRNA concentration is optimally adapted to codon usage
      when the concentration of different tRNA species matches the square-root of the
      frequency of their corresponding synonymous codons. When tRNA concentration and
      codon usage are well adapted to each other, the optimal content of all tRNA
      species carrying the same amino acid should match the square-root of the
      frequency of the amino acid. These predictions are examined against empirical
      data from Escherichia coli, Salmonella typhimurium, and Saccharomyces cerevisiae.

PMID- 9584085
TI  - Yeast dom34 mutants are defective in multiple developmental pathways and exhibit
      decreased levels of polyribosomes.
AB  - The DOM34 gene of Saccharomyces cerevisiae is similar to genes found in diverse
      eukaryotes and archaebacteria. Analysis of dom34 strains shows that progression
      through the G1 phase of the cell cycle is delayed, mutant cells enter meiosis
      aberrantly, and their ability to form pseudohyphae is significantly diminisehd.
      RPS30A, which encodes ribosomal protein S30, was identified in a screen for high
      copy suppressors of the dom34delta growth defect. dom34delta mutants display an
      altered polyribosome profile that is rescued by expression of RPS30A. Taken
      together, these data indicate that Dom34p functions in protein translation to
      promote G1 progression and differentiation. A Drosophila homolog of Dom34p,
      pelota, is required for the proper coordination of meiosis and spermatogenesis.
      Heterologous expression of pelota in dom34delata mutants restores wild-type
      growth and differentiation, suggesting conservation of function between the
      eukaryotic members of the gene family.

PMID- 9584086
TI  - Regulation of yeast glycogen metabolism and sporulation by Glc7p protein
      phosphatase.
AB  - Glc7p is an essential serine/threonine type 1 protein phosphatase (PP1) from the
      yeast Saccharomyces cerevisiae, which has a role in many processes including cell
      cycle progression, sporulation, glycogen accumulation, translation initiation,
      and glucose repression. Two hallmarks of PP1 enzymes are very high amino acid
      sequence conservation and association of the catalytic subunit with a variety of
      noncatalytic, regulatory subunits. We tested the hypothesis that PP1 sequence
      conservation was the result of each PP1 residue playing a role in multiple
      intermolecular interactions. Analysis of 24 glc7 mutants, isolated primarily by
      their glycogen accumulation traits, revealed that every mutated Glc7p residue
      altered many noncatalytic subunit affinities and conferred unselected sporulation
      traits to various degrees. Furthermore, quantitative analysis showed that Glc7p
      affinity for the glycogen-binding noncatalytic subunit Gac1p was not the only
      parameter that determines the glycogen accumulation by a glc7 mutant. Sds22p is
      one Glc7p noncatalytic subunit that is essential for mitotic growth.
      Surprisingly, several mutant Glc7p proteins had undetectable affinity for Sds22p,
      yet grew apparently normally. The characterization of glc7 diploid sporulation
      revealed that Glc7p has at least two meiotic roles. Premeiotic DNA synthesis was
      undetectable in glc7 mutants with the poorest sporulation. In the glc7 diploids
      examined, expression of the meiotic inducer IME1 was proportional to the glc7
      diploid sporulation frequency. Moreover, IME1 hyperexpression could not suppress
      glc7 sporulation traits. The Glc7p/Gip1p holoenzyme may participate in completion
      of meiotic divisions or spore packaging because meiotic dyads predominate when
      some glc7 diploids sporulate.

PMID- 9584088
TI  - Inherited and environmentally induced differences in mutation frequencies between
      wild strains of Sordaria fimicola from "Evolution Canyon".
AB  - We have studied whether there is natural genetic variation for mutation
      frequencies, and whether any such variation is environment-related. Mutation
      frequencies differed significantly between wild strains of the fungus Sordaria
      fimicola isolated from a harsher or a milder microscale environment in "Evolution
      Canyon," Israel. Strains from the harsher, drier, south-facing slope had higher
      frequencies of new spontaneous mutations and of accumulated mutations than
      strains from the milder, lusher, north-facing slope. Collective total mutation
      frequencies over many loci for ascospore pigmentation were 2.3, 3.5 and 4.4% for
      three strains from the south-facing slope, and 0.9, 1.1, 1.2, 1.3 and 1.3% for
      five strains from the north-facing slope. Some of this between-slope difference
      was inherited through two generations of selfing, with average spontaneous
      mutation frequencies of 1.9% for south-facing slope strains and 0.8% for north
      facing slope strains. The remainder was caused by different frequencies of
      mutations arising in the original environments. There was also significant
      heritable genetic variation in mutation frequencies within slopes. Similar
      between-slope differences were found for ascospore germination-resistance to
      acriflavine, with much higher frequencies in strains from the south-facing slope.
      Such inherited variation provides a basis for natural selection for optimum
      mutation rates in each environment.

PMID- 9584087
TI  - Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore
      components.
AB  - CP1 (encoded by CEP1) is a Saccharomyces cerevisiae chromatin protein that binds
      a DNA element conserved in centromeres and in the 5'-flanking DNA of methionine
      biosynthetic (MET) genes. Strains lacking CP1 are defective in chromosome
      segregation and MET gene transcription, leading to the hypothesis that CP1 plays
      a general role in assembling higher order chromatin structures at genomic sites
      where it is bound. A screen for mutations synthetically lethal with a cep1 null
      allele yielded five recessive csl (cep1 synthetic lethal) mutations, each
      defining a unique complementation group. Four of the five mutations
      synergistically increased the loss rate of marker chromosomes carrying a
      centromere lacking the CP1 binding site, suggesting that the cep1 synthetic
      lethality was due to chromosome segregation defects. Three of these four CSL
      genes were subsequently found to be known or imputed kinetochore genes: CEP3,
      NDC10, and CSE4. The fourth, CSL4, corresponded to ORF YNL232w on chromosome XIV,
      and was found to be essential. A human cDNA was identified that encoded a protein
      homologous to Csl4 and that complemented the csl4-1 mutation. The results are
      consistent with the view that the major cellular role of CP1 is to safeguard the
      biochemical integrity of the kinetochore.

PMID- 9584089
TI  - A screen for dynein synthetic lethals in Aspergillus nidulans identifies spindle
      assembly checkpoint genes and other genes involved in mitosis.
AB  - Cytoplasmic dynein is a ubiquitously expressed microtubule motor involved in
      vesicle transport, mitosis, nuclear migration, and spindle orientation. In the
      filamentous fungus Aspergillus nidulans, inactivation of cytoplasmic dynein,
      although not lethal, severely impairs nuclear migration. The role of dynein in
      mitosis and vesicle transport in this organism is unclear. To investigate the
      complete range of dynein function in A. nidulans, we searched for synthetic
      lethal mutations that significantly reduced growth in the absence of dynein but
      had little effect on their own. We isolated 19 sld (synthetic lethality without
      dynein) mutations in nine different genes. Mutations in two genes exacerbate the
      nuclear migration defect seen in the absence of dynein. Mutations in six other
      genes, including sldA and sldB, show a strong synthetic lethal interaction with a
      mutation in the mitotic kinesin bimC and, thus, are likely to play a role in
      mitosis. Mutations in sldA and sldB also confer hypersensitivity to the
      microtubule-destabilizing drug benomyl. sldA and sldB were cloned by
      complementation of their mutant phenotypes using an A. nidulans autonomously
      replicating vector. Sequencing revealed homology to the spindle assembly
      checkpoint genes BUB1 and BUB3 from Saccharomyces cerevisiae. Genetic interaction
      between dynein and spindle assembly checkpoint genes, as well as other mitotic
      genes, indicates that A. nidulans dynein plays a role in mitosis. We suggest a
      model for dynein motor action in A. nidulans that can explain dynein involvement
      in both mitosis and nuclear distribution.

PMID- 9584090
TI  - The isolation and characterization of nrc-1 and nrc-2, two genes encoding protein
      kinases that control growth and development in Neurospora crassa.
AB  - Using an insertional mutagenesis approach, a series of Neurospora crassa mutants
      affected in the ability to control entry into the conidiation developmental
      program were isolated. One such mutant, GTH16-T4, was found to lack normal
      vegetative hyphae and to undergo constitutive conidiation. The affected gene has
      been named nrc-1, for nonrepressible conidiation gene #1. The nrc-1 gene was
      cloned from the mutant genomic DNA by plasmid rescue, and was found to encode a
      protein closely related to the protein products of the Saccharomyces cerevisiae
      STE11 and Schizosaccharomyces pombe byr2 genes. Both of these genes encode MAPKK
      kinases that are necessary for sexual development in these organisms. We conclude
      the nrc-1 gene encodes a MAPKK kinase that functions to repress the onset of
      conidiation in N. crassa. A second mutant, GTH16-T17, was found to lack normal
      vegetative hyphae and to constitutively enter, but not complete, the conidiation
      program. The affected locus is referred to as nrc-2 (nonrepressible conidiation
      gene #2). The nrc-2 gene was cloned and found to encode a serine-threonine
      protein kinase. The kinase is closely related to the predicted protein products
      of the S. pombe kad5, and the S. cerevisiae YNRO47w and KIN82 genes, three genes
      that have been identified in genome sequencing projects. The N. crassa nrc-2 gene
      is the first member of this group of kinases for which a phenotype has been
      defined. We conclude a functional nrc-2-encoded serine/threonine kinase is
      required to repress entry into the conidiation program.

PMID- 9584091
TI  - The homeobox gene cut interacts genetically with the homeotic genes proboscipedia
      and Antennapedia.
AB  - The cut locus (ct) codes for a homeodomain protein (Cut) and controls the
      identity of a subset of cells in the peripheral nervous system in Drosophila.
      During a screen to identify ct-interacting genes, we observed that flies
      containing a hypomorphic ct mutation and a heterozygous deletion of the
      Antennapedia complex exhibit a transformation of mouthparts into leg and antennal
      structures similar to that seen in homozygous proboscipedia (pb) mutants. The
      same phenotype is produced with all heterozygous pb alleles tested and is fully
      penetrant in two different ct mutant backgrounds. We show that this phenotype is
      accompanied by pronounced changes in the expression patterns of both ct and pb in
      labial discs. Furthermore, a significant proportion of ct mutant flies that are
      heterozygous for certain Antennapedia (Antp) alleles have thoracic defects that
      mimic loss-of-function Antp phenotypes, and ectopic expression of Cut in antennal
      discs results in ectopic Antp expression and a dominant Antp-like phenotype. Our
      results implicate ct in the regulation of expression and/or function of two
      homeotic genes and document a new role of ct in the control of segmental
      identity.

PMID- 9584092
TI  - Male sterility and meiotic drive associated with sex chromosome rearrangements in
      Drosophila. Role of X-Y pairing.
AB  - In Drosophila melanogaster, deletions of the pericentromeric X heterochromatin
      cause X-Y nondisjunction, reduced male fertility and distorted sperm recovery
      ratios (meiotic drive) in combination with a normal Y chromosome and interact
      with Y-autosome translocations (T(Y;A)) to cause complete male sterility. The
      pericentromeric heterochromatin has been shown to contain the male-specific X-Y
      meiotic pairing sites, which consist mostly of a 240-bp repeated sequence in the
      intergenic spacers (IGS) of the rDNA repeats. The experiments in this paper
      address the relationship between X-Y pairing failure and the meiotic drive and
      sterility effects of Xh deletions. X-linked insertions either of complete rDNA
      repeats or of rDNA fragments that contain the IGS were found to suppress X-Y
      nondisjunction and meiotic drive in Xh-/Y males, and to restore fertility to Xh
      /T(Y;A) males for eight of nine tested Y-autosome translocations. rDNA fragments
      devoid of IGS repeats proved incapable of suppressing either meiotic drive or
      chromosomal sterility. These results indicate that the various spermatogenic
      disruptions associated with X heterochromatic deletions are all consequences of X
      Y pairing failure. We interpret these findings in terms of a novel model in which
      misalignment of chromosomes triggers a checkpoint that acts by disabling the
      spermatids that derive from affected spermatocytes.

PMID- 9584093
TI  - Mapping of Drosophila mutations using site-specific male recombination.
AB  - Although recombination does not usually occur in the male Drosophila germline,
      site-specific recombination can be induced at the ends of P elements. This
      finding suggested that male recombination could be used to map Drosophila
      mutations. In this article, we describe the general method and its application to
      the mapping of two EMS-induced female-sterile mutations, grauzone and cortex.
      Within two months, the grauzone gene was mapped relative to seven different P
      element insertion sites, and cortex was mapped relative to 23 different P
      elements. The results allowed us to map grauzone to a region of about 50 kb, and
      cortex distal to the chromosomal region 33E. These experiments demonstrate that P
      element-induced site-specific male recombination is an efficient and general
      method to map Drosophila autosomal mutations.

PMID- 9584094
TI  - Molecular and behavioral analysis of four period mutants in Drosophila
      melanogaster encompassing extreme short, novel long, and unorthodox arrhythmic
      types.
AB  - Of the mutationally defined rhythm genes in Drosophila melanogaster, period (per)
      has been studied the most. We have molecularly characterized three older per
      mutants-perT, perClk, and per04-along with a novel long-period one (perSLIH).
      Each mutant is the result of a single nucleotide change. perT, perClk, and
      perSLIH are accounted for by amino acid substitutions; per04 is altered at a
      splice site acceptor and causes aberrant splicing. perSLIH exhibits a long period
      of 27 hr in constant darkness and entrains to light/dark (L/D) cycles with a
      later-than-normal evening peak of locomotion. perSLIH males are more rhythmic
      than females. perSLIH's clock runs faster at higher temperatures and slower at
      lower ones, exhibiting a temperature-compensation defect opposite to that of
      perLong. The per-encoded protein (PER) in the perT mutant cycles in L/D with an
      earlier-than-normal peak; this peak in perSLIH is later than normal, and there
      was a slight difference in the PER timecourse of males vs. females. PER in per04
      was undetectable. Two of these mutations, perSLIH and perClk, lie within regions
      of PER that have not been studied previously and may define important functional
      domains of this clock protein.

PMID- 9584095
TI  - Factors affecting transposition of the Himar1 mariner transposon in vitro.
AB  - Mariner family transposable elements are widespread in animals, but their
      regulation is poorly understood, partly because only two are known to be
      functional. These are particular copies of the Dmmar1 element from Drosophila
      mauritiana, for example, Mos1, and the consensus sequence of the Himar1 element
      from the horn fly, Haematobia irritans. An in vitro transposition system was
      refined to investigate several parameters that influence the transposition of
      Himar1. Transposition products accumulated linearly over a period of 6 hr.
      Transposition frequency increased with temperature and was dependent on Mg2+
      concentration. Transposition frequency peaked over a narrow range of transposase
      concentration. The decline at higher concentrations, a phenomenon observed in
      vivo with Mos1, supports the suggestion that mariners may be regulated in part by
      "overproduction inhibition." Transposition frequency decreased exponentially with
      increasing transposon size and was affected by the sequence of the flanking DNA
      of the donor site. A noticeable bias in target site usage suggests a preference
      for insertion into bent or bendable DNA sequences rather than any specific
      nucleotide sequences beyond the TA target site.

PMID- 9584096
TI  - Genetic polymorphism and natural selection in the malaria parasite Plasmodium
      falciparum.
AB  - We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that
      are considered potential targets for specific antimalarial vaccines. The
      polymorphism is unevenly distributed among the loci; loci encoding proteins
      expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1,
      MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the
      sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1).
      Comparison of synonymous and nonsynonymous substitutions indicates that natural
      selection may account for the polymorphism observed at seven of the 10 loci
      studied. This inference depends on the assumption that synonymous substitutions
      are neutral, which we test by analyzing codon bias and G+C content in a set of 92
      gene loci. We find evidence for an overall trend towards increasing A+T richness,
      but no evidence for mutation bias. Although the neutrality of synonymous
      substitutions is not definitely established, this trend towards an A+T rich
      genome cannot explain the accumulation of substitutions at least in the case of
      four genes (AMA-1, CSP, LSA-1, and PF48/45) because the Gleft and right arrow C
      transversions are more frequent than expected. Moreover, the Tajima test
      manifests positive natural selection for the MSP-1 and, less strongly, MSP-3
      polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1
      and PF48/45. We conclude that there is definite evidence for positive natural
      selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four
      other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No
      evidence for natural selection is found for Pfs25.

PMID- 9584097
TI  - Identification of chromosomal regions involved in decapentaplegic function in
      Drosophila.
AB  - Signaling molecules of the transforming growth factor beta (TGF-beta) family
      contribute to numerous developmental processes in a variety of organisms.
      However, our understanding of the mechanisms which regulate the activity of and
      mediate the response to TGF-beta family members remains incomplete. The product
      of the Drosophila decapentaplegic (dpp) locus is a well-characterized member of
      this family. We have taken a genetic approach to identify factors required for
      TGF-beta function in Drosophila by testing for genetic interactions between
      mutant alleles of dpp and a collection of chromosomal deficiencies. Our survey
      identified two deficiencies that act as maternal enhancers of recessive embryonic
      lethal alleles of dpp. The enhanced individuals die with weakly ventralized
      phenotypes. These phenotypes are consistent with a mechanism whereby the
      deficiencies deplete two maternally provided factors required for dpp's role in
      embryonic dorsal-ventral pattern formation. One of these deficiencies also
      appears to delete a factor required for dpp function in wing vein formation.
      These deficiencies remove material from the 54F-55A and 66B-66C polytene
      chromosomal regions, respectively. As neither of these regions has been
      previously implicated in dpp function, we propose that each of the deficiencies
      removes a novel factor or factors required for dpp function.

PMID- 9584098
TI  - Genes expressed in the ring gland, the major endocrine organ of Drosophila
      melanogaster.
AB  - We have used an enhancer-trap approach to begin characterizing the function of
      the Drosophila endocrine system during larval development. Five hundred and ten
      different lethal PZ element insertions were screened to identify those in which a
      reporter gene within the P element showed strong expression in part or all of the
      ring gland, the major site of production and release of developmental hormones,
      and which had a mutant phenotype consistent with an endocrine defect. Nine strong
      candidate genes were identified in this screen, and eight of these are expressed
      in the lateral cells of the ring gland that produce ecdysteroid molting hormone
      (EC). We have confirmed that the genes detected by these enhancer traps are
      expressed in patterns similar to those detected by the reporter gene. Two of the
      genes encode proteins, protein kinase A and calmodulin, that have previously been
      implicated in the signaling pathway leading to EC synthesis and release in other
      insects. A third gene product, the translational elongation factor EF-1alpha F1,
      could play a role in the translational regulation of EC production. The screen
      also identified the genes couch potato and tramtrack, previously known from their
      roles in peripheral nervous system development, as being expressed in the ring
      gland. One enhancer trap revealed expression of the gene encoding the C subunit
      of vacuolar ATPase (V-ATPase) in the medial cells of the ring gland, which
      produce the juvenile hormone that controls progression through developmental
      stages. This could reveal a function of V-ATPase in the response of this part of
      the ring gland to adenotropic neuropeptides. However, the gene identified by this
      enhancer trap is ubiquitously expressed, suggesting that the enhancer trap is
      detecting only a subset of its control elements. The results show that the
      enhancer trap approach can be a productive way of exploring tissue-specific
      genetic functions in Drosophila.

PMID- 9584099
TI  - Evidence for a genomic imprinting sex determination mechanism in Nasonia
      vitripennis (Hymenoptera; Chalcidoidea).
AB  - Five different models have been proposed for the sex determination mechanism of
      Chalcidoidea (Hymenoptera). Except for the most recently proposed model (genomic
      imprinting sex determination; GISD), each of these models has required
      complicating additions to explain observed phenomena. This report provides the
      first experimental test of the GISD model while simultaneously examining the four
      previously proposed models of sex determination. This test utilizes the parasitic
      wasp Nasonia vitripennis, crossing polyploid females with males harboring the
      paternal sex ratio chromosome (PSR). The results of this study support the GISD
      model as the mechanism of sex determination in Chalcidoidea. Specifically,
      crosses demonstrate that sex determination is independent of embryonic
      heterozygosity, ploidy, and gametic syngamy but is directly correlated with the
      embryonic presence of correctly imprinted chromosomes of paternal origin. These
      crossing experiments also provide information about the poorly characterized
      mechanisms of PSR, a supernumerary chromosome that induces paternal autosome loss
      in early embryos. The results demonstrate that the poor transmission of PSR
      through females is not a result of the ploidy of the host but of an alternative
      sex-dependent process. Crossing data reveal that PSR consistently induces the
      loss of the entire paternal complement that it accompanies, regardless of whether
      this complement is haploid or diploid.

PMID- 9584100
TI  - Multigene family of ribosomal DNA in Drosophila melanogaster reveals contrasting
      patterns of homogenization for IGS and ITS spacer regions. A possible mechanism
      to resolve this paradox.
AB  - The multigene family of rDNA in Drosophila reveals high levels of within-species
      homogeneity and between-species diversity. This pattern of mutation distribution
      is known as concerted evolution and is considered to be due to a variety of
      genomic mechanisms of turnover (e.g., unequal crossing over and gene conversion)
      that underpin the process of molecular drive. The dynamics of spread of mutant
      repeats through a gene family, and ultimately through a sexual population,
      depends on the differences in rates of turnover within and between chromosomes.
      Our extensive molecular analysis of the intergenic spacer (IGS) and internal
      transcribed spacer (ITS) spacer regions within repetitive rDNA units, drawn from
      the same individuals in 10 natural populations of Drosophila melanogaster
      collected along a latitudinal cline on the east coast of Australia, indicates a
      relatively fast rate of X-Y and X-X interchromosomal exchanges of IGS length
      variants in agreement with a multilineage model of homogenization. In contrast,
      an X chromosome-restricted 24-bp deletion in the ITS spacers is indicative of the
      absence of X-Y chromosome exchanges for this region that is part of the same
      repetitive rDNA units. Hence, a single lineage model of homogenization, coupled
      to drift and/or selection, seems to be responsible for ITS concerted evolution. A
      single-stranded exchange mechanism is proposed to resolve this paradox, based on
      the role of the IGS region in meiotic pairing between X and Y chromosomes in D.
      melanogaster.

PMID- 9584102
TI  - Mapping the genome of a model protochordate. I. A low resolution genetic map
      encompassing the fusion/histocompatibility (Fu/HC) locus of Botryllus schlosseri.
AB  - The colonial protochordate, Botryllus schlosseri, undergoes a genetically
      defined, natural transplantation reaction when the edges of two growing colonies
      interact. Peripheral blood vessels of each colony touch and will either fuse
      together to form a common vasculature between the colonies, or reject each other
      in an active blood-based inflammatory process in which the interacting vessels
      are cut off and the two colonies no longer interact. Previous studies have
      demonstrated that allorecognition in Botryllus is principally controlled by a
      single Mendelian locus named the fusion/histocompatibility (Fu/HC) locus, with
      multiple codominantly expressed alleles. However, identification and cloning of
      this locus has been difficult. We are taking a genomic approach in isolating this
      locus by creating a detailed genetic linkage map of the 725 Mbp Botryllus genome
      using DNA polymorphisms (primarily identified as AFLPs) as molecular genetic
      markers. DNA polymorphisms are identified in inbred laboratory strains of Fu/HC
      defined Botryllus, and their segregation and linkage is analyzed in a series of
      defined crosses. Using bulk segregant analysis, we have focused our mapping
      efforts on the Fu/HC region of the genome, and have generated an initial map
      which delineates the Fu/HC locus to a 5.5 cM region.

PMID- 9584101
TI  - white+ transgene insertions presenting a dorsal/ventral pattern define a single
      cluster of homeobox genes that is silenced by the polycomb-group proteins in
      Drosophila melanogaster.
AB  - We used the white gene as an enhancer trap and reporter of chromatin structure.
      We collected white+ transgene insertions presenting a peculiar pigmentation
      pattern in the eye: white expression is restricted to the dorsal half of the eye,
      with a clear-cut dorsal/ventral (D/V) border. This D/V pattern is stable and
      heritable, indicating that phenotypic expression of the white reporter reflects
      positional information in the developing eye. Localization of these transgenes
      led us to identify a unique genomic region encompassing 140 kb in 69D1-3 subject
      to this D/V effect. This region contains at least three closely related homeobox
      containing genes that are constituents of the iroquois complex (IRO-C). IRO-C
      genes are coordinately regulated and implicated in similar developmental
      processes. Expression of these genes in the eye is regulated by the products of
      the Polycomb-group (Pc-G) and trithorax-group (trx-G) genes but is not modified
      by classical modifiers of position-effect variegation. Our results, together with
      the report of a Pc-G binding site in 69D, suggest that we have identified a novel
      cluster of target genes for the Pc-G and trx-G products. We thus propose that
      ventral silencing of the whole IRO-C in the eye occurs at the level of chromatin
      structure in a manner similar to that of the homeotic gene complexes, perhaps by
      local compaction of the region into a heterochromatin-like structure involving
      the Pc-G products.

PMID- 9584103
TI  - Genetic identification of multiple loci that control breast cancer susceptibility
      in the rat.
AB  - We have used a rat model of induced mammary carcinomas in an effort to identify
      breast cancer susceptibility genes. Using genetic crosses between the carcinoma
      resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have
      confirmed the identification of the Mcs1 locus that modulates tumor number. We
      have now also identified two additional loci, Mcs2 and Mcs3. These three loci map
      to chromosomes 2, 7, and 1, respectively, and interact additively to suppress
      mammary carcinoma development in the COP strain. They are responsible for a major
      portion of the tumor-resistant phenotype of the COP rat. No loss of
      heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4,
      has also been identified on chromosome 8 and acts in contrast to increase the
      number of carcinomas. These results show that mammary carcinoma susceptibility in
      the COP rat is a polygenic trait. Interestingly, a polymorphism in the human
      genomic region homologous to the rat Mcs4 region is associated with an increased
      breast cancer risk in African-American women. The isolation of the Mcs genes may
      help elucidate novel mechanisms of carcinogenesis, provide information important
      for human breast cancer risk estimation, and also provide unique drug discovery
      targets for breast cancer prevention.

PMID- 9584104
TI  - Bayesian inference of genetic parameters and selection response for litter size
      components in pigs.
AB  - Three contemporary lines were formed from the progeny of 50 French Large White
      sows. In the first line, gilts were selected for ovulation rate at puberty. In
      the second line, they were selected for prenatal survival of the first two
      parities, corrected for ovulation rate. The control constituted the third line.
      Ovulation rate at puberty was analyzed using an animal model with a batch effect.
      Prenatal survival was analyzed with a repeatability animal model that included
      batch and parity effects. Flat priors were used to represent vague previous
      knowledge about parity and batch effects. Additive and residual effects were
      represented assuming that they were a priori normally distributed. Variance
      components were assumed to follow either uniform or inverted chi-square
      distributions, a priori. The use of different priors did not affect the results
      substantially. Heritabilities for ovulation rate ranged from 0.32 to 0.39, and
      from 0.11 to 0.16 for prenatal survival, depending on the prior used. The mean of
      the marginal posterior distribution of response to four generations of selection
      ranged from 0.38 to 0.40 ova per generation, and from 1.1 to 1.3% of the mean
      survival rate for average survival per generation.

PMID- 9584106
TI  - Molecular mapping of segregation distortion loci in Aegilops tauschii.
AB  - Distorted segregation ratios of genetic markers are often observed in progeny of
      inter- and intraspecific hybrids and may result from competition among gametes or
      from abortion of the gamete or zygote. In this study, 194 markers mapped in an
      Aegilops tauschii F2 population were surveyed for distorted segregation ratios.
      Region(s) with skewed segregation ratios were detected on chromosomes 1D, 3D, 4D,
      and 7D. These distorter loci are designated as QSd.ksu-1D, QSd. ksu-3D, QSd.ksu
      4D, and QSd.ksu-7D. Three regions of segregation distortion identified on
      chromosome 5D were analyzed in two sets of reciprocal backcross populations to
      analyze the effect of sex and cytoplasm on segregation distortion. Extreme
      distortion of marker segregation ratios was observed in populations in which the
      F1 was used as the male parent, and ratios were skewed in favor of TA1691
      alleles. There was some evidence of differential transmission caused by nucleo
      cytoplasmic interactions. Our results agree with other studies stating that loci
      affecting gametophyte competition in male gametes are located on 5DL. The
      distorter loci on 5DL are designated as QSd.ksu-5D.1, QSd.ksu-5D.2, and QSd.ksu
      5D.3.

PMID- 9584105
TI  - A DNA methyltransferase homolog with a chromodomain exists in multiple
      polymorphic forms in Arabidopsis.
AB  - Chromodomains are thought to mediate protein-protein interactions between
      chromatin components. We have detected a chromodomain embedded within the
      catalytic region of a predicted Arabidopsis DNA methyltransferase that is
      diverged from other eukaryotic enzymes. The 791 residue "chromomethylase" (CMT1)
      is encoded by a floral transcript that is spliced from 20 exons and is present at
      only approximately 1/10(-7) of total mRNA. Genomic sequencing reveals an ancient
      haplotype split at CMT1 between Col-0 + Metz and the other ecotypes examined. In
      the Col-0 + Metz haplotype, alternative mRNA processing at intron 13 truncates
      the coding region. In Ler, RLD, and No-0, similar truncation is caused by
      insertion of an intact retrotransposon, Evelknievel, which is present as a single
      copy in Ler and RLD and is currently methylated and inactive. Evelknievel is
      found at this site on a single branch that connects the Ler, RLD, and No-0
      ecotypes but is absent from the genomes of all other ecotypes examined. A stop
      codon within exon 6 of the Metz ecotype confirms that CMT1 is nonessential.
      Nevertheless, comparison to CMT1 of Cardaminopsis arenosa, an outcrossing
      relative, indicates conservation for DNA methyltransferase function. We discuss
      how allelic diversity of CMT1 may reflect loosened selective constraints in a
      self-fertilizing species such as Arabidopsis thaliana.

PMID- 9584107
TI  - Transcriptionally active MuDR, the regulatory element of the mutator transposable
      element family of Zea mays, is present in some accessions of the Mexican land
      race Zapalote chico.
AB  - To date, mobile Mu transposons and their autonomous regulator MuDR have been
      found only in the two known Mutator lines of maize and their immediate
      descendants. To gain insight into the origin, organization, and regulation of
      Mutator elements, we surveyed exotic maize and related species for cross
      hybridization to MuDR. Some accessions of the mexican land race Zapalote chico
      contain one to several copies of full-length, unmethylated, and transcriptionally
      active MuDR-like elements plus non-autonomous Mu elements. The sequenced 5.0-kb
      MuDR-Zc element is 94.6% identical to MuDR, with only 20 amino acid changes in
      the 93-kD predicted protein encoded by mudrA and ten amino acid changes in the 23
      kD predicted protein of mudrB. The terminal inverted repeat (TIR) A of MuDR-Zc is
      identical to standard MuDR; TIRB is 11.2% divergent from TIRA. In Zapalote chico,
      mudrA transcripts are very rare, while mudrB transcripts are as abundant as in
      Mutator lines with a few copies of MuDR. Zapalote chico lines with MuDR-like
      elements can trans-activate reporter alleles in inactive Mutator backgrounds;
      they match the characteristic increased forward mutation frequency of standard
      Mutator lines, but only after outcrossing to another line. Zapalote chico
      accessions that lack MuDR-like elements and the single copy MuDR a1-mum2 line
      produce few mutations. New mutants recovered from Zapalote chico are somatically
      stable.

PMID- 9584108
TI  - Plastome mutator-induced alterations arise in Oenothera chloroplast DNA through
      template slippage.
AB  - The plastome mutator of Oenothera hookeri strain Johansen causes deletions and
      duplications at target sites defined by direct repeats in the plastid genome.
      Previous studies characterized the mutations long after they had occurred and
      could not discriminate between the possibilities that the plastome mutator acted
      through unequal homologous recombination or template slippage. From the known
      hotspots, the rRNA spacer in the large inverted repeat was chosen for this study
      because it contains both direct and indirect repeats. Identical deletions were
      recovered from independently derived plants; the altered regions were always
      flanked by direct repeats. The regions in which the deletions occurred have the
      potential to form secondary structures that would stabilize the intervening
      sequence. Of the two affected regions, the one with the stronger potential
      secondary structure was altered more frequently. Because no duplication products
      or inversions were recovered, it is proposed that the plastome mutator acts
      through template slippage rather than through a recombination mechanism.

PMID- 9584109
TI  - Intron loss and gain during evolution of the catalase gene family in angiosperms.
AB  - Angiosperms (flowering plants), including both monocots and dicots, contain small
      catalase gene families. In the dicot, Arabidopsis thaliana, two catalase (CAT)
      genes, CAT1 and CAT3, are tightly linked on chromosome 1 and a third, CAT2, which
      is more similar to CAT1 than to CAT3, is unlinked on chromosome 4. Comparison of
      positions and numbers of introns among 13 angiosperm catalase genomic sequences
      indicates that intron positions are conserved, and suggests that an ancestral
      catalase gene common to monocots and dicots contained seven introns. Arabidopsis
      CAT2 has seven introns; both CAT1 and CAT3 have six introns in positions
      conserved with CAT2, but each has lost a different intron. We suggest the
      following sequence of events during the evolution of the Arabidopsis catalase
      gene family. An initial duplication of an ancestral catalase gene gave rise to
      CAT3 and CAT1. CAT1 then served as the template for a second duplication,
      yielding CAT2. Intron losses from CAT1 and CAT3 followed these duplications. One
      subclade of monocot catalases has lost all but the 5'-most and 3'-most introns,
      which is consistent with a mechanism of intron loss by replacement of an
      ancestral intron-containing gene with a reverse-transcribed DNA copy of a fully
      spliced mRNA. Following this event of concerted intron loss, the Oryza sativa
      (rice, a monocot) CAT1 lineage acquired an intron in a novel position, consistent
      with a mechanism of intron gain at proto-splice sites.

PMID- 9584110
TI  - Quantitative trait loci affecting differences in floral morphology between two
      species of monkeyflower (Mimulus).
AB  - Conspicuous differences in floral morphology are partly responsible for
      reproductive isolation between two sympatric species of monkeyflower because of
      their effect on visitation of the flowers by different pollinators. Mimulus
      lewisii flowers are visited primarily by bumblebees, whereas M. cardinalis
      flowers are visited mostly by hummingbirds. The genetic control of 12
      morphological differences between the flowers of M. lewisii and M. cardinalis was
      explored in a large linkage mapping population of F2 plants n = 465 to provide an
      accurate estimate of the number and magnitude of effect of quantitative trait
      loci (QTLs) governing each character. Between one and six QTLs were identified
      for each trait. Most (9/12) traits appear to be controlled in part by at least
      one major QTL explaining >/=25% of the total phenotypic variance. This implies
      that either single genes of individually large effect or linked clusters of genes
      with a large cumulative effect can play a role in the evolution of reproductive
      isolation and speciation.

PMID- 9584111
TI  - Quantitative trait locus (QTL) mapping using different testers and independent
      population samples in maize reveals low power of QTL detection and large bias in
      estimates of QTL effects.
AB  - The efficiency of marker-assisted selection (MAS) depends on the power of
      quantitative trait locus (QTL) detection and unbiased estimation of QTL effects.
      Two independent samples N = 344 and 107 of F2 plants were genotyped for 89 RFLP
      markers. For each sample, testcross (TC) progenies of the corresponding F3 lines
      with two testers were evaluated in four environments. QTL for grain yield and
      other agronomically important traits were mapped in both samples. QTL effects
      were estimated from the same data as used for detection and mapping of QTL
      (calibration) and, based on QTL positions from calibration, from the second,
      independent sample (validation). For all traits and both testers we detected a
      total of 107 QTL with N = 344, and 39 QTL with N = 107, of which only 20 were in
      common. Consistency of QTL effects across testers was in agreement with
      corresponding genotypic correlations between the two TC series. Most QTL
      displayed no significant QTL x environment nor epistatic interactions. Estimates
      of the proportion of the phenotypic and genetic variance explained by QTL were
      considerably reduced when derived from the independent validation sample as
      opposed to estimates from the calibration sample. We conclude that, unless QTL
      effects are estimated from an independent sample, they can be inflated, resulting
      in an overly optimistic assessment of the efficiency of MAS.

PMID- 9584112
TI  - Circadian expression of the maize catalase Cat3 gene is highly conserved among
      diverse maize genotypes with structurally different promoters.
AB  - The Cat3 gene of maize exhibits a transcriptionally regulated circadian rhythm.
      In the present study we examined the following: (1) the extent of the circadian
      Cat3 expression between maize genotypes of diverse origin; (2) the functional
      significance of a Tourist transposable element located in the Cat3 promoter of
      the inbred line W64A, which harbors putative regulatory elements (GATA repeat,
      CCAAT boxes) shown to be involved in the light induction and circadian regulation
      of the Arabidopsis CAB2, as well as other plant genes; and (3) aspects of the
      physiological role of CAT-3 in maize metabolism. Results confirm that the
      circadian Cat3 expression is a general phenomenon in maize. Regulation of Cat3
      gene expression is not dependent on the presence of the Tourist element in the
      promoter of the gene nor on the presence of motifs similar to those found
      significant in the circadian expression of the Arabidopsis CAB2 gene. Structural
      diversity was revealed in the Cat3 promoters of maize genotypes of diverse
      origins. However, highly conserved regions with putative regulatory motifs were
      identified. Relevance of the conserved regions to the circadian regulation of the
      gene is discussed. Possible physiological roles of CAT-3 are suggested.

PMID- 9584113
TI  - Isolation and characterization of Arabidopsis mutants defective in the induction
      of ethylene biosynthesis by cytokinin.
AB  - Cytokinins elevate ethylene biosynthesis in etiolated Arabidopsis seedlings via a
      post-transcriptional modification of one isoform of the key biosynthetic enzyme
      ACC synthase. In order to begin to dissect the signaling events leading from
      cytokinin perception to this modification, we have isolated a series of mutants
      that lack the ethylene-mediated triple response in the presence of cytokinin due
      to their failure to increase ethylene biosynthesis. Analysis of genetic
      complementation and mapping revealed that these Cin mutants (cytokinin
      insensitive) represent four distinct complementation groups, one of which, cin4,
      is allelic to the constitutive photomorphogenic mutant fus9/cop10. The Cin
      mutants have subtle effects on the morphology of adult plants. We further
      characterized the Cin mutants by analyzing ethylene biosynthesis in response to
      various other inducers and in adult tissues, as well as by assaying additional
      cytokinin responses. The cin3 mutant did not disrupt ethylene biosynthesis under
      any other conditions, nor did it disrupt any other cytokinin responses. Only cin2
      disrupted ethylene biosynthesis in multiple circumstances. cin1 and cin2 made
      less anthocyanin in response to cytokinin. cin1 also displayed reduced shoot
      initiation in tissue culture in response to cytokinin, suggesting that it affects
      a cytokinin signaling element.

PMID- 9584114
TI  - Maximum likelihood estimation of population growth rates based on the coalescent.
AB  - We describe a method for co-estimating 4Nemu (four times the product of effective
      population size and neutral mutation rate) and population growth rate from
      sequence samples using Metropolis-Hastings sampling. Population growth (or
      decline) is assumed to be exponential. The estimates of growth rate are biased
      upwards, especially when 4Nemu is low; there is also a slight upwards bias in the
      estimate of 4Nemu itself due to correlation between the parameters. This bias
      cannot be attributed solely to Metropolis-Hastings sampling but appears to be an
      inherent property of the estimator and is expected to appear in any approach
      which estimates growth rate from genealogy structure. Sampling additional
      unlinked loci is much more effective in reducing the bias than increasing the
      number or length of sequences from the same locus.

PMID- 9584115
TI  - Testing for epistasis between deleterious mutations.
AB  - Determining the way in which deleterious mutations interact in their effects on
      fitness is crucial to numerous areas in population genetics and evolutionary
      biology. For example, if each additional mutation leads to a greater decrease in
      log fitness than the last (synergistic epistasis), then the evolution of sex and
      recombination may be favored to facilitate the elimination of deleterious
      mutations. However, there is a severe shortage of relevant data. Three relatively
      simple experimental methods to test for epistasis between deleterious mutations
      in haploid species have recently been proposed. These methods involve crossing
      individuals and examining the mean and/or skew in log fitness of the offspring
      and parents. The main aim of this paper is to formalize these methods, and
      determine the most effective way in which tests for epistasis could be carried
      out. We show that only one of these methods is likely to give useful results:
      crossing individuals that have very different numbers of deleterious mutations,
      and comparing the mean log fitness of the parents with that of their offspring.
      We also reconsider experimental data collected on Chlamydomonas moewussi using
      two of the three methods. Finally, we suggest how the test could be applied to
      diploid species.

PMID- 9584116
TI  - Assessing the impact of secondary structure and solvent accessibility on protein
      evolution.
AB  - Empirically derived models of amino acid replacement are employed to study the
      association between various physical features of proteins and evolution. The
      strengths of these associations are statistically evaluated by applying the
      models of protein evolution to 11 diverse sets of protein sequences. Parametric
      bootstrap tests indicate that the solvent accessibility status of a site has a
      particularly strong association with the process of amino acid replacement that
      it experiences. Significant association between secondary structure environment
      and the amino acid replacement process is also observed. Careful description of
      the length distribution of secondary structure elements and of the organization
      of secondary structure and solvent accessibility along a protein did not always
      significantly improve the fit of the evolutionary models to the data sets that
      were analyzed. As indicated by the strength of the association of both solvent
      accessibility and secondary structure with amino acid replacement, the process of
      protein evolution-both above and below the species level-will not be well
      understood until the physical constraints that affect protein evolution are
      identified and characterized.

PMID- 9584117
TI  - pha-4 is Ce-fkh-1, a fork head/HNF-3alpha,beta,gamma homolog that functions in
      organogenesis of the C. elegans pharynx.
AB  - The C. elegans Ce-fkh-1 gene has been cloned on the basis of its sequence
      similarity to the winged-helix DNA binding domain of the Drosophila fork head and
      mammalian HNF-3alpha,beta,gamma genes, and mutations in the zygotically active
      pha-4 gene have been shown to block formation of the pharynx (and rectum) at an
      early stage in embryogenesis. In the present paper, we show that Ce-fkh-1 and pha
      4 are the same gene. We show that PHA-4 protein is present in nuclei of
      essentially all pharyngeal cells, of all five cell types. PHA-4 protein first
      appears close to the point at which a cell lineage will produce only pharyngeal
      cells, independently of cell type. We show that PHA-4 binds directly to a 'pan
      pharyngeal enhancer element' previously identified in the promoter of the
      pharyngeal myosin myo-2 gene; in transgenic embryos, ectopic PHA-4 activates
      ectopic myo-2 expression. We also show that ectopic PHA-4 can activate ectopic
      expression of the ceh-22 gene, a pharyngeal-specific NK-2-type homeodomain
      protein previously shown to bind a muscle-specific enhancer near the PHA-4
      binding site in the myo-2 promoter. We propose that it is the combination of pha
      4 and regulatory molecules such as ceh-22 that produces the specific gene
      expression patterns during pharynx development. Overall, pha-4 can be described
      as an 'organ identity factor', completely necessary for organ formation, present
      in all cells of the organ from the earliest stages, capable of integrating
      upstream developmental pathways (in this case, the two distinct pathways that
      produce the anterior and posterior pharynx) and participating directly in the
      transcriptional regulation of organ specific genes. Finally, we note that the
      distribution of PHA-4 protein in C. elegans embryos is remarkably similar to the
      distribution of the fork head protein in Drosophila embryos: high levels in the
      foregut/pharynx and hindgut/rectum; low levels in the gut proper. Moreover, we
      show that pha-4 expression in the C. elegans gut is regulated by elt-2, a C.
      elegans gut-specific GATA-factor and possible homolog of the Drosophila gene
      serpent, which influences fork head expression in the fly gut. Overall, our
      results provide evidence for a highly conserved pathway regulating formation of
      the digestive tract in all (triploblastic) metazoa.

PMID- 9584118
TI  - Eyeless initiates the expression of both sine oculis and eyes absent during
      Drosophila compound eye development.
AB  - The Drosophila Pax-6 gene eyeless acts high up in the genetic hierarchy involved
      in compound eye development and can direct the formation of extra eyes in ectopic
      locations. Here we identify sine oculis and eyes absent as two mediators of the
      eye-inducing activity of eyeless. We show that eyeless induces and requires the
      expression of both genes independently during extra eye development. During
      normal eye development, eyeless is expressed earlier than and is required for the
      expression of sine oculis and eyes absent, but not vice versa. Based on the
      results presented here and those of others, we propose a model in which eyeless
      induces the initial expression of both sine oculis and eyes absent in the eye
      disc. sine oculis and eyes absent then appear to participate in a positive
      feedback loop that regulates the expression of all three genes. In contrast to
      the regulatory interactions that occur in the developing eye disc, we also show
      that in the embryonic head, sine oculis acts in parallel to eyeless and twin of
      eyeless, a second Pax-6 gene from Drosophila. Recent studies in vertebrate
      systems indicate that the epistatic relationships among the corresponding
      vertebrate homologs are very similar to those observed in Drosophila.

PMID- 9584119
TI  - Spatial and temporal targeting of gene expression in Drosophila by means of a
      tetracycline-dependent transactivator system.
AB  - In order to evaluate the efficiency of the tetracycline-regulated gene expression
      system in Drosophila, we have generated transgenic lines expressing a
      tetracycline-controlled transactivator protein (tTA), with specific expression
      patterns during embryonic and larval development. These lines were used to direct
      expression of a tTA-responsive promoter fused to the coding region of either the
      beta-galactosidase or the homeotic protein Antennapedia (ANTP), under various
      conditions of tetracycline treatment. We found that expression of beta
      galactosidase can be efficiently inhibited in embryos and larvae with
      tetracycline provided in the food, and that a simple removal of the larvae from
      tetracycline exposure results in the induction of the enzyme in a time- and
      concentration-dependent manner. Similar treatments can be used to prevent the
      lethality associated with the ectopic expression of ANTP in embryos and,
      subsequently, to control the timing of expression of the homeoprotein ANTP
      specifically in the antennal imaginal disc. Our results show that the expression
      of a gene placed under the control of a tetracycline-responsive promoter can be
      tightly controlled, both spatially by the regulatory sequences driving the
      expression of tTA and temporally by tetracycline. This provides the basis of a
      versatile binary system for controlling gene expression in Drosophila, with an
      additional level of regulation as compared to the general method using the yeast
      transcription factor GAL4.

PMID- 9584120
TI  - Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic
      hedgehog.
AB  - Within the developing vertebrate nervous system, it is not known how progenitor
      cells interpret the positional information provided by inducing signals or how
      the domains in which distinct groups of neural cells differentiate are defined.
      Gli proteins may be involved in these processes. In the frog neural plate, we
      have previously shown that the zinc finger transcription factor Gli1 is expressed
      in midline cells and mediates the effects of Shh inducing floor plate
      differentiation. In contrast, Gli2 and Gli3 are expressed throughout the neural
      plate except for the midline. Here, it is shown that Gli3 and Shh repress each
      other whereas Gli2, like Gli1, is a target of Shh signaling. However, only Gli1
      can induce the differentiation of floor plate cells. In addition, Gli2 and Gli3
      repress the ectopic induction of floor plate cells by Gli1 in co-injection assays
      and inhibit endogenous floor plate differentiation. The definition of the floor
      plate domain, therefore, appears to be defined by the antagonizing activities of
      Gli2 and Gli3 on Gli1 function. Because both Gli1 and Gli2 are induced by Shh,
      these results establish a regulatory feedback loop triggered by Shh that
      restricts floor plate cells to the midline. We have also previously shown that
      the Gli genes induce neuronal differentiation and here it is shown that there is
      specificity to the types of neurons the Gli proteins induce. Only Gli1 induces
      Nkx2.1/TTF-1(+) ventral forebrain neurons. Moreover, Gli2 and Gli3 inhibit their
      differentiation. In contrast, the differentiation of spinal motor neurons can be
      induced by the two ventrally expressed Gli genes, Gli1 and Gli2, suggesting that
      Gli2 directly mediates induction of motor neurons by Shh. In addition, Gli3
      inhibits motor neuron differentiation by Gli2. Thus, combinatorial Gli function
      may pattern the neural tube, integrating positional information and cell type
      differentiation.

PMID- 9584121
TI  - Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to
      arrested differentiation of pancreatic beta cells.
AB  - The endocrine pancreas is organized into clusters of cells called islets of
      Langerhans comprising four well-defined cell types: alpha beta, delta and PP
      cells. While recent genetic studies indicate that islet development depends on
      the function of an integrated network of transcription factors, the specific
      roles of these factors in early cell-type specification and differentiation
      remain elusive. Nkx2.2 is a member of the mammalian NK2 homeobox transcription
      factor family that is expressed in the ventral CNS and the pancreas. Within the
      pancreas, we demonstrate that Nkx2.2 is expressed in alpha, beta and PP cells,
      but not in delta cells. In addition, we show that mice homozygous for a null
      mutation of Nkx2.2 develop severe hyperglycemia and die shortly after birth.
      Immunohistochemical analysis reveals that the mutant embryos lack insulin
      producing beta cells and have fewer glucagon-producing alpha cells and PP cells.
      Remarkably, in the mutants there remains a large population of islet cells that
      do not produce any of the four endocrine hormones. These cells express some beta
      cell markers, such as islet amyloid polypeptide and Pdx1, but lack other
      definitive beta cell markers including glucose transporter 2 and Nkx6.1. We
      propose that Nkx2.2 is required for the final differentiation of pancreatic beta
      cells, and in its absence, beta cells are trapped in an incompletely
      differentiated state.

PMID- 9584122
TI  - Developmental regulation of heterochromatin-mediated gene silencing in
      Drosophila.
AB  - The roles of differentiation, mitotic activity and intrinsic promoter strength in
      the maintenance of heterochromatic silencing were investigated during development
      using an inducible lacZ gene as an in vivo probe. Heterochromatic silencing is
      initiated at the onset of gastrulation, approximately 1 hour after
      heterochromatin is first visible cytologically. A high degree of silencing is
      maintained in the mitotically active imaginal cells from mid-embryogenesis until
      early third instar larval stage, and extensive relaxation of silencing is tightly
      associated with the onset of differentiation. Relaxation of silencing can be
      triggered in vitro by ecdysone. In contrast, timing and extent of silencing at
      both the initiation and relaxation stages are insensitive to changes in cell
      cycle activity, and intrinsic promoter strength also does not influence the
      extent of silencing by heterochromatin. These data suggest that the silencing
      activity of heterochromatin is developmentally programmed.

PMID- 9584123
TI  - Specification of the hypaxial musculature.
AB  - During development of the amniote embryo, the dorsolateral territory of the
      somite is destined to give rise to the hypaxial skeletal musculature. To study
      the mechanisms that lead to the formation of this musculature, we cloned the
      chick Lbx1 gene that is specific to prospective hypaxial myoblasts at occipital,
      cervical and limb levels. Using this gene as a marker, we characterised the
      anatomical structures that produce the signals necessary for the specification of
      the hypaxial musculature by ablating them or transplanting them to ectopic
      locations in the chick embryo. In addition, we inserted BMP4 soaked beads medial
      to the somite. Our data suggest that lateralising signals from intermediate and
      lateral mesoderm have to synergise with dorsalising signals from the surface
      ectoderm to induce the formation of the hypaxial musculature. However, the
      lateralising function of the lateral mesoderm can only in part be mimicked by
      BMP4.

PMID- 9584124
TI  - In vivo clonal analyses reveal the properties of endogenous neural stem cell
      proliferation in the adult mammalian forebrain.
AB  - The adult mammalian forebrain contains a population of multipotential neural stem
      cells in the subependyma of the lateral ventricles whose progeny are the
      constitutively proliferating cells, which divide actively throughout life. The
      adult mammalian brain is ideal for examining the kinetics of the stem cells due
      to their strict spatial localization and the limited and discrete type of progeny
      generated (constitutively proliferating cells). Clonal lineage analyses 6 days
      after retrovirus infection revealed that under baseline conditions 60% of the
      constitutively proliferating cells undergo cell death, 25% migrate to the
      olfactory bulb and 15% remain confined to the lateral ventricle subependyma
      (where they reside for approximately 15 days). Analysis of single cell clones 31
      days after retroviral infection revealed that the stem cell divides
      asymmetrically to self-renew and give rise to constitutively proliferating cells.
      Following repopulation of the depleted subependyma the average clone size is 2.8
      times larger than control, yet the absolute number of cells migrating to the
      olfactory bulb is maintained and the stem cell retains its asymmetric mode of
      division. The number of neural stem cells in the adult forebrain 33 days after
      repopulation of the subependyma was estimated using bromodeoxyuridine labeling of
      subepenydmal cells. There were calculated to be 1200-1300 cells between the
      rostral corpus callosum and rostral anterior commissure; these data support a
      lineage model similar to those based on stem cell behavior in other tissue types.

PMID- 9584125
TI  - Identifying loci required for follicular patterning using directed mosaics.
AB  - We have developed a 'directed mosaic' system in Drosophila by using the GAL4
      system to control the expression of the yeast recombinase, FLP, in a spatial and
      temporal fashion. By directing FLP expression, we show that it is possible to
      efficiently and specifically target loss-of-function studies for vital loci to
      the developmental pathway of interest. A simple F1 adult phenotypic screen
      demonstrated that most adult tissues can be analyzed with this approach. Using
      GAL4 lines expressed during oogenesis, we have refined the system to examine the
      roles of vital loci in the development of the follicular epithelium. We have
      identified essential genes involved in egg chamber organization, cell migration
      and cell shape. Further, we have used this technique to gain insights into the
      role of the Drosophila EGF receptor pathway in establishing the egg axes.
      Finally, using different UAS-FLP, GAL4 and existing FRT lines, we have built
      stocks that permit the analysis of approximately 95% of the genome in follicular
      mosaics.

PMID- 9584126
TI  - Altered imprinted gene methylation and expression in completely ES cell-derived
      mouse fetuses: association with aberrant phenotypes.
AB  - In vitro manipulation of preimplantation mammalian embryos can influence
      differentiation and growth at later stages of development. In the mouse, culture
      of embryonic stem (ES) cells affects their totipotency and may give rise to fetal
      abnormalities. To investigate whether this is associated with epigenetic
      alterations in imprinted genes, we analysed two maternally expressed genes
      (Igf2r, H19) and two paternally expressed genes (Igf2, U2af1-rs1) in ES cells and
      in completely ES cell-derived fetuses. Altered allelic methylation patterns were
      detected in all four genes, and these were consistently associated with allelic
      changes in gene expression. All the methylation changes that had arisen in the ES
      cells persisted on in vivo differentiation to fetal stages. Alterations included
      loss of methylation with biallelic expression of U2af1-rs1, maternal methylation
      and predominantly maternal expression of Igf2, and biallelic methylation and
      expression of Igf2r. In many of the ES fetuses, the levels of H19 expression were
      strongly reduced, and this biallelic repression was associated with biallellic
      methylation of the H19 upstream region. Surprisingly, biallelic H19 repression
      was not associated with equal levels of Igf2 expression from both parental
      chromosomes, but rather with a strong activation of the maternal Igf2 allele. ES
      fetuses derived from two of the four ES lines appeared developmentally
      compromised, with polyhydramnios, poor mandible development and interstitial
      bleeding and, in chimeric fetuses, the degree of chimerism correlated with
      increased fetal mass. Our study establishes a model for how early embryonic
      epigenetic alterations in imprinted genes persist to later developmental stages,
      and are associated with aberrant phenotypes.

PMID- 9584127
TI  - Tissue layer and organ specificity of trichome formation are regulated by GLABRA1
      and TRIPTYCHON in Arabidopsis.
AB  - In animal development, cellular diversity is generated within tissues which in
      turn are derived from germ layers. Similar to the germ layers in animals, plants
      establish three distinct tissue layers early in development which each give rise
      to a distinct set of cell types. To investigate the role of tissue-layer-specific
      cues in generating plant cellular diversity we studied the spatial regulation of
      an epidermal cell type, trichomes (hairs), by the two genes, GLABRA1 (GL1) and
      TRIPTYCHON (TRY). Ubiquitous expression of the positive regulator GL1 in the
      absence of the negative regulator TRY leads to ectopic trichome formation not
      only on additional organs but also in subepidermal tissue layers. Trichomes in
      inner tissue layers can differentiate the same morphology and show a spacing
      pattern comparable to trichomes in the epidermis. This clearly shows that cell
      type specification takes place downstream of tissue-specific cues. We propose a
      model of how the tissue and organ specificity of trichome induction is regulated
      in normal development.

PMID- 9584128
TI  - YakA, a protein kinase required for the transition from growth to development in
      Dictyostelium.
AB  - When Dictyostelium cells starve they arrest their growth and induce the
      expression of genes necessary for development. We have identified and
      characterized a protein kinase, YakA, that is essential for the proper regulation
      of both events. Amino acid sequence and functional similarities indicate that
      YakA is a homolog of Yak1p, a growth-regulating protein kinase in S. cerevisiae.
      Purified YakA expressed in E. coli is able to phosphorylate myelin basic protein.
      YakA-null cells are smaller and their cell cycle is accelerated relative to wild
      type cells. When starved, YakA-null cells fail to decrease the expression of the
      growth-stage gene cprD, and do not induce the expression of genes required for
      the earliest stages of development. YakA mRNA levels increase during exponential
      growth and reach a maximum at the point of starvation, consistent with a role in
      mediating starvation responses. YakA mRNA also accumulates when cells are grown
      in medium conditioned by cells grown to high density, suggesting that yakA
      expression is under the control of an extracellular signal that accumulates
      during growth. Expression of yakA from a conditional promoter causes cell-cycle
      arrest in nutrient-rich medium and promotes developmental events, such as the
      expression of genes required for cAMP signaling. YakA appears to regulate the
      transition from growth to development in Dictyostelium.

PMID- 9584129
TI  - Regulation of dopa decarboxylase expression during colour pattern formation in
      wild-type and melanic tiger swallowtail butterflies.
AB  - The eastern tiger swallowtail butterfly Papilio glaucus shows a striking example
      of Batesian mimicry. In this species, females are either wild type (yellow and
      black) or melanic (where most of the yellow colour is replaced by black). In
      order to understand how these different colour patterns are regulated, we
      examined the temporal order of wing pigment synthesis via precursor incorporation
      studies, enzyme assays, and in situ hybridisation to mRNA encoding a key enzyme,
      dopa decarboxylase. We show that dopa decarboxylase provides dopamine to both of
      the two major colour pigments, papiliochrome (yellow) and melanin (black).
      Interestingly, however, dopa decarboxylase activity is spatially and temporally
      regulated, being utilised early in presumptive yellow tissues and later in black.
      Further, in melanic females, both dopa decarboxylase activity and early
      papiliochrome synthesis are suppressed in the central forewing and this normally
      yellow area is later melanised. These results show that the regulation of enzyme
      synthesis observed in the yellow/black pattern of a single wing, is similar to
      that involved in melanism. We infer that dopa decarboxylase activity must be
      regulated in concert with downstream enzymes of either the melanin and/or the
      papiliochrome specific pathways, forming part of a developmental switch between
      yellow or black. This modification of multiple enzyme activities in concert is
      consistent with a model of melanisation involving coordinate regulation of the
      underlying synthetic pathways by a single Y-linked (female) factor.

PMID- 9584130
TI  - The hem of the embryonic cerebral cortex is defined by the expression of multiple
      Wnt genes and is compromised in Gli3-deficient mice.
AB  - In the developing vertebrate CNS, members of the Wnt gene family are
      characteristically expressed at signaling centers that pattern adjacent parts of
      the neural tube. To identify candidate signaling centers in the telencephalon, we
      isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon.
      In situ hybridization experiments demonstrate that one of the isolated Wnt genes,
      Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three
      others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the
      medial edge of the telencephalon, defining the hem of the cerebral cortex. The
      Wnt-rich cortical hem is a transient, neuron-containing, neuroepithelial
      structure that forms a boundary between the hippocampus and the telencephalic
      choroid plexus epithelium (CPe) throughout their embryonic development.
      Indicating a close developmental relationship between the cortical hem and the
      CPe, Wnt gene expression is upregulated in the cortical hem both before and just
      as the CPe begins to form, and persists until birth. In addition, although the
      cortical hem does not show features of differentiated CPe, such as expression of
      transthyretin mRNA, the CPe and cortical hem are linked by shared expression of
      members of the Bmp and Msx gene families. In the extra-toesJ (XtJ) mouse mutant,
      telencephalic CPe fails to develop. We show that Wnt gene expression is deficient
      at the cortical hem in XtJ/XtJ mice, but that the expression of other
      telencephalic developmental control genes, including Wnt7a, is maintained. The
      XtJ mutant carries a deletion in Gli3, a vertebrate homolog of the Drosophila
      gene cubitus interruptus (ci), which encodes a transcriptional regulator of the
      Drosophila Wnt gene, wingless. Our observations indicate that Gli3 participates
      in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss
      of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem
      that include Wnt gene misregulation.

PMID- 9584131
TI  - Local induction of patterning and programmed cell death in the developing
      Drosophila retina.
AB  - Local cell signaling can pattern the nervous system by directing cell fates,
      including programmed cell death. In the developing Drosophila retina, programmed
      cell death is used to remove excess cells between ommatidia. Cell ablation
      revealed the source and position of signals required for regulating the pattern
      of programmed cell death among these interommatidial cells. Two types of signals
      regulate this patterning event. Notch-mediated signals between interommatidial
      precursors result in removal of unneeded cells. Cone cells and primary pigment
      cells oppose this signal by supplying a 'life'-promoting activity; evidence is
      provided that this signal occurs through localized activation of the EGF
      Receptor/Ras pathway. Together, these signals refine the highly regular pattern
      observed in the adult retina.

PMID- 9584132
TI  - Interactions of EGF, Wnt and HOM-C genes specify the P12 neuroectoblast fate in
      C. elegans.
AB  - We investigate how temporal and spatial interactions between multiple
      intercellular and intracellular factors specify the fate of a single cell in
      Caenorhabditis elegans. P12, which is a ventral cord neuroectoblast, divides
      postembryonically to generate neurons and a unique epidermal cell. Three classes
      of proteins are involved in the specification of P12 fate: the LIN-3/LET-23
      epidermal growth factor signaling pathway, a Wnt protein LIN-44 and its candidate
      receptor LIN-17, and a homeotic gene product EGL-5. We show that LIN-3 is an
      inductive signal sufficient to promote the P12 fate, and the conserved EGF
      signaling pathway is utilized for P12 fate specification; egl-5 is a downstream
      target of the lin-3/let-23 pathway in specifying P12 fate; and LIN-44 and LIN-17
      act synergistically with lin-3 in the specification of the P12 fate. The Wnt
      pathway may function early in development to regulate the competence of the cells
      to respond to the LIN-3 inductive signal.

PMID- 9584133
TI  - Cross-tolerance: a pathway for inducing tolerance to peripheral tissue antigens.

PMID- 9584134
TI  - CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone
      marrow-derived antigen-presenting cells.
AB  - T cell tolerance to parenchymal self-antigens is thought to be induced by
      encounter of the T cell with its cognate peptide-major histocompatibility complex
      (MHC) ligand expressed on the parenchymal cell, which lacks appropriate
      costimulatory function. We have used a model system in which naive T cell
      receptor (TCR) transgenic hemagglutinin (HA)-specific CD4+ T cells are adoptively
      transferred into mice expressing HA as a self-antigen on parenchymal cells. After
      transfer, HA-specific T cells develop a phenotype indicative of TCR engagement
      and are rendered functionally tolerant. However, T cell tolerance is not induced
      by peptide-MHC complexes expressed on parenchymal cells. Rather, tolerance
      induction requires that HA is presented by bone marrow (BM)-derived cells. These
      results indicate that tolerance induction to parenchymal self-antigens requires
      transfer to a BM-derived antigen-presenting cell that presents it to T cells in a
      tolerogenic fashion.

PMID- 9584135
TI  - Murine cutaneous mastocytosis and epidermal melanocytosis induced by keratinocyte
      expression of transgenic stem cell factor.
AB  - The growth and differentiation of mast cells and melanocytes require stem cell
      factor (SCF), the ligand for the kit receptor tyrosine kinase. SCF may exist as a
      membrane-bound or soluble molecule. Abnormalities of the SCF-kit signaling
      pathway, with increased local concentrations of soluble SCF, have been implicated
      in the pathogenesis of the human disease cutaneous mastocytosis, but have not yet
      been shown to play a causal role. To investigate both the potential of SCF to
      cause mastocytosis and its role in epidermal melanocyte homeostasis, we targeted
      the expression of SCF to epidermal keratinocytes in mice with two different
      transgenes controlled by the human keratin 14 promoter. The transgenes contained
      cDNAs that either produced SCF, which can exist in both membrane-bound and
      soluble forms, or SCF, which remains essentially membrane bound. Murine epidermal
      keratinocyte expression of membrane-bound/ soluble SCF reproduced the phenotype
      of human cutaneous mastocytosis, with dermal mast cell infiltrates and epidermal
      hyperpigmentation, and caused the maintenance of a population of melanocytes in
      the interadnexal epidermis, an area where melanocytes and melanin are found in
      human skin but where they are not typically found in murine skin. Expression of
      membrane-bound SCF alone resulted in epidermal melanocytosis and melanin
      production, but did not by itself cause mastocytosis. We conclude, first, that a
      phenotype matching that of human mastocytosis can be produced in mice by
      keratinocyte overproduction of soluble SCF, suggesting a potential cause of this
      disease. Second, we conclude that keratinocyte expression of membrane-bound SCF
      results in the postnatal maintenance of epidermal melanocytes in mice. Since the
      resulting animals have skin that more closely approximates human skin than do
      normal mice, their study may be more relevant to human melanocyte biology than
      the study of skin of normal mice.

PMID- 9584136
TI  - Long-term persistence of activated cytotoxic T lymphocytes after viral infection
      of the central nervous system.
AB  - Mice intranasally inoculated with influenza A/X-31 are protected against a
      subsequent intracerebral challenge with the neurovirulent influenza A/WSN and
      this heterotypic protection is mediated by CD8(+) cytotoxic T lymphocytes. We
      have studied the kinetics of this secondary immune response and found that
      despite the elimination of replication-competent virus by day 10, we were able to
      recover activated influenza-specific cytotoxic T lymphocytes (CTLs) that killed
      freshly ex vivo from the brains of mice for at least 320 d after the
      intracerebral inoculation. The activated antiviral CTLs expressed high levels of
      the early activation marker CD69, suggesting continuing TCR signaling despite a
      lack of viral protein and major histocompatibility complex staining by
      immunohistochemistry in the brain parenchyma and barely detectable levels of
      viral nucleic acid by single and two-step reverse transcription PCR. Local
      persistence of activated lymphocytes may be important for efficient long-term
      responses to viruses prone to recrudesce in sites of relative immune privilege.

PMID- 9584137
TI  - Defective acidification in human breast tumor cells and implications for
      chemotherapy.
AB  - Multidrug resistance (MDR) is a significant problem in the treatment of cancer.
      Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug
      sensitive cells but are excluded from the nucleus in drug-resistant cells,
      concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g.,
      anthracyclines and vinca alkaloids) should concentrate in acidic organelles. This
      report presents a quantification of the pH for identified compartments of the MCF
      7 human breast tumor cell line and demonstrates that (a) the chemotherapeutic
      Adriamycin concentrates in acidified organelles of drug-resistant but not drug
      sensitive cells; (b) the lysosomes and recycling endosomes are not acidified in
      drug-sensitive cells; (c) the cytosol of drug-sensitive cells is 0.4 pH units
      more acidic than the cytosol of resistant cells; and (d) disrupting the
      acidification of the organelles of resistant cells with monensin, bafilomycin A1,
      or concanamycin A is sufficient to change the Adriamycin distribution to that
      found in drug-sensitive cells, rendering the cell vulnerable once again to
      chemotherapy. These results suggest that acidification of organelles is causally
      related to drug resistance and is consistent with the hypothesis that
      sequestration of drugs in acidic organelles and subsequent extrusion from the
      cell through the secretory pathways contribute to chemotherapeutic resistance.

PMID- 9584138
TI  - Adherence of erythrocytes during exflagellation of Plasmodium falciparum
      microgametes is dependent on erythrocyte surface sialic acid and glycophorins.
AB  - Malaria male gametocytes within a newly ingested infected blood meal in the
      mosquito midgut emerge from erythrocytes and extrude approximately eight
      flagellar microgametes in a process termed exflagellation. In culture, and in
      blood removed from infected patients, emerging microgametes avidly adhere to
      neighboring uninfected and infected erythrocytes, as well as to emerged female
      macrogametes, creating "exflagellation centers". The mechanism of erythrocyte
      adherence is not known nor has it been determined for what purpose microgametes
      may bind to erythrocytes. The proposition of a function underlying erythrocyte
      adherence is supported by the observation of species-specificity in adhesion:
      microgametes of the human malaria Plasmodium falciparum can bind human
      erythrocytes but not chicken erythrocytes, whereas avian host Plasmodium
      gallinaceum microgametes bind chicken but not human erythrocytes. In this study
      we developed a binding assay in which normal, enzyme-treated, variant or null
      erythrocytes are identified by a cell surface fluorescent label and assayed for
      adherence to exflagellating microgametes. Neuraminidase, trypsin or ficin
      treatment of human erythrocytes eliminated their ability to adhere to Plasmodium
      falciparum microgametes, suggesting a role of sialic acid and one or more
      glycophorins in the binding to a putative gamete receptor. Using nulls lacking
      glycophorin A [En(a-)], glycophorin B (S-s-U-) or a combination of glycophorin A
      and B (Mk/Mk) we showed that erythrocytes lacking glycophorin B retain the
      ability to bind but a lack of glycophorin A reduced adherence by exflagellating
      microgametes. We propose that either the sialic acid moiety of glycophorins,
      predominantly glycophorin A, or a more complex interaction involving the
      glycophorin peptide backbone, is the erythrocyte receptor for adhesion to
      microgametes.

PMID- 9584139
TI  - Abortive proliferation of rare T cells induced by direct or indirect antigen
      presentation by rare B cells in vivo.
AB  - Antigen-specific B cells are implicated as antigen-presenting cells in memory and
      tolerance responses because they capture antigens efficiently and localize to T
      cell zones after antigen capture. It has not been possible, however, to visualize
      the effect of specific B cells on specific CD4+ helper T cells under
      physiological conditions. We demonstrate here that rare T cells are activated in
      vivo by minute quantities of antigen captured by antigen-specific B cells.
      Antigen-activated B cells are helped under these conditions, whereas antigen
      tolerant B cells are killed. The T cells proliferate and then disappear
      regardless of whether the B cells are activated or tolerant. We show genetically
      that T cell activation, proliferation, and disappearance can be mediated either
      by transfer of antigen from antigen-specific B cells to endogenous antigen
      presenting cells or by direct B-T cell interactions. These results identify a
      novel antigen presentation route, and demonstrate that B cell presentation of
      antigen has profound effects on T cell fate that could not be predicted from in
      vitro studies.

PMID- 9584140
TI  - HIV-1 selection by epidermal dendritic cells during transmission across human
      skin.
AB  - Macrophage tropic HIV-1 is predominant during the initial viremia after person to
      person transmission of HIV-1 (Zhu, T., H. Mo, N. Wang, D.S. Nam, Y. Cao, R.A.
      Koup, and D.D. Ho. 1993. Science. 261:1179-1181.), and this selection may occur
      during virus entry and carriage to the lymphoid tissue. Human skin explants were
      used to model HIV-1 selection that may occur at the skin or mucosal surface.
      Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the
      abraded epidermis were recovered from the cells emigrating from the skin
      explants. Dermis and epidermis were separated by dispase digestion after virus
      exposure to determine the site of viral selection within the skin. Uptake and
      transmission to T cells of all HIV-1 isolates was found with the dermal emigrant
      cells, but only macrophage tropic virus was transferred by emigrants from the
      epidermis exposed to HIV-1, indicating selection only within the epidermis. CD3+,
      CD4+ T cells were found in both the dermal and epidermal emigrant cells. After
      cell sorting to exclude contaminating T cells, macrophage tropic HIV-1 was found
      in both the dermal emigrant dendritic cells and in dendritic cells sorted from
      the epidermal emigrants. These observations suggest that selective infection of
      the immature epidermal dendritic cells represents the cellular mechanism that
      limits the initial viremia to HIV-1 that can use the CCR5 coreceptor.

PMID- 9584141
TI  - Characterization of human CD8+ T cells reactive with Mycobacterium tuberculosis
      infected antigen-presenting cells.
AB  - Previous studies in murine models, including those using the beta2 microglobulin
      knockout mouse, have suggested an important role for CD8+ T cells in host defense
      to Mycobacterium tuberculosis (Mtb). At present, little is understood about these
      cells in the human immune response to tuberculosis. This report demonstrates the
      existence of human Mtb-reactive CD8+ T cells. These cells are present
      preferentially in persons infected with Mtb and produce interferon gamma in
      response to stimulation with Mtb-infected target cells. Recognition of Mtb
      infected cells by these CD8+ T cells is restricted neither by the major
      histocompatibility complex (MHC) class I A, B, or C alleles nor by CD1, although
      it is inhibited by anti-MHC class I antibody. The Mtb-specific CD8+ T cells
      recognize an antigen which is generated in the proteasome, but which does not
      require transport through the Golgi-ER. The data suggest the possible use of
      nonpolymorphic MHC class Ib antigen presenting structures other than CD1.

PMID- 9584142
TI  - Inactivation of a defined active site in the mouse 20S proteasome complex
      enhances major histocompatibility complex class I antigen presentation of a
      murine cytomegalovirus protein.
AB  - Proteasomes generate peptides bound by major histocompatibility complex (MHC)
      class I molecules. Avoiding proteasome inhibitors, which in most cases do not
      distinguish between individual active sites within the cell, we used a molecular
      genetic approach that allowed for the first time the in vivo analysis of defined
      proteasomal active sites with regard to their significance for antigen
      processing. Functional elimination of the delta/low molecular weight protein
      (LMP) 2 sites by substitution with a mutated inactive LMP2 T1A subunit results in
      reduced cell surface expression of the MHC class I H-2Ld and H-2Dd molecules.
      Surface levels of H-2Ld and H-2Dd molecules were restored by external loading
      with peptides. However, as a result of the active site mutation, MHC class I
      presentation of a 9-mer peptide derived from a protein of murine cytomegalovirus
      was enhanced about three- to fivefold. Our experiments provide evidence that the
      delta/LMP2 active site elimination limits the processing and presentation of
      several peptides, but may be, nonetheless, beneficial for the generation and
      presentation of others.

PMID- 9584143
TI  - Protective immunity does not correlate with the hierarchy of virus-specific
      cytotoxic T cell responses to naturally processed peptides.
AB  - Infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV)
      stimulates major histocompatibility complex class I-restricted cytotoxic T cells
      (CTLs), which normally resolve the infection. Three peptide epitopes derived from
      LCMV have been shown to bind the mouse class I molecule H-2 Db and to stimulate
      CTL responses in LCMV-infected mice. This report describes the identity and
      abundance of each CTL epitope after their elution from LCMV-infected cells. Based
      on this information, peptide abundance was found to correlate with the magnitude
      of each CTL response generated after infection with LCMV. Subsequent experiments,
      performed to determine the antiviral capacity of each CTL specificity, indicate
      that the quantitative hierarchy of CTL activity does not correlate with the
      ability to protect against LCMV infection. This report, therefore, indicates that
      immunodominant epitopes should be defined, not only by the strength of the CTL
      response that they stimulate, but also by the ability of the CTLs to protect
      against infection.

PMID- 9584144
TI  - The effect of class II major histocompatibility complex expression on adherence
      of Helicobacter pylori and induction of apoptosis in gastric epithelial cells: a
      mechanism for T helper cell type 1-mediated damage.
AB  - Helicobacter pylori infection is associated with gastric epithelial damage,
      including apoptosis, ulceration, and cancer. Although bacterial factors and the
      host response are believed to contribute to gastric disease, no receptor has been
      identified that explains how the bacteria attach and signal the host cell to
      undergo apoptosis. Using H. pylori as "bait" to capture receptor proteins in
      solubilized membranes of gastric epithelial cells, class II major
      histocompatibility complex (MHC) molecules were identified as a possible
      receptor. Signaling through class II MHC molecules leading to the induction of
      apoptosis was confirmed using cross-linking IgM antibodies to surface class II
      MHC molecules. Moreover, binding of H. pylori and the induction of apoptosis were
      inhibited by antibodies recognizing class II MHC. Since type 1 T helper cells are
      present during infection and produce interferon (IFN)-gamma, which increases
      class II MHC expression, gastric epithelial cell lines were exposed to H. pylori
      in the presence or absence of IFN-gamma. IFN-gamma increased the attachment of
      the bacteria as well as the induction of apoptosis in gastric epithelial cells.
      In contrast to MHC II-negative cell lines, H. pylori induced apoptosis in cells
      expressing class II MHC molecules constitutively or after gene transfection.
      These data describe a novel receptor for H. pylori and provide a mechanism by
      which bacteria and the host response interact in the pathogenesis of gastric
      epithelial cell damage.

PMID- 9584145
TI  - Roles of the tumor suppressor p53 and the cyclin-dependent kinase inhibitor
      p21WAF1/CIP1 in receptor-mediated apoptosis of WEHI 231 B lymphoma cells.
AB  - Treatment of WEHI 231 immature B lymphoma cells with an antibody against their
      surface immunoglobulin M (anti-IgM) induces apoptosis and has been studied
      extensively as a model of self-induced B cell tolerance. Since the tumor
      suppressor protein p53 has been implicated in apoptosis in a large number of cell
      types and has been found to be mutated in a variety of B cell tumors, here we
      sought to determine whether p53 and the p53 target gene cyclin-dependent kinase
      inhibitor p21(WAF1/CIP1) were involved in anti-IgM-induced cell death. Anti-IgM
      treatment of WEHI 231 cells increased expression of p53 and p21 protein levels.
      Ectopic expression of wild-type p53 in WEHI 231 cells induced both p21 expression
      and apoptosis. Ectopic expression of p21 similarly induced apoptosis. Rescue of
      WEHI 231 cells from apoptosis by costimulation with CD40 ligand ablated the
      increase in p21 expression. Lastly, a significant decrease in anti-IgM-mediated
      apoptosis was seen upon downregulation of endogenous p53 activity by expression
      of a dominant-negative p53 protein or upon microinjection of an antisense p21
      expression vector or antibody. Taken together, the above data demonstrate
      important roles for p53 and p21 proteins in receptor-mediated apoptosis of WEHI
      231 B cells.

PMID- 9584146
TI  - Modulation of natural killer cell cytotoxicity in human cytomegalovirus
      infection: the role of endogenous class I major histocompatibility complex and a
      viral class I homolog.
AB  - Natural killer (NK) cells have been implicated in early immune responses against
      certain viruses, including cytomegalovirus (CMV). CMV causes downregulation of
      class I major histocompatibility complex (MHC) expression in infected cells;
      however, it has been proposed that a class I MHC homolog encoded by CMV, UL18,
      may act as a surrogate ligand to prevent NK cell lysis of CMV-infected cells. In
      this study, we examined the role of UL18 in NK cell recognition and lysis using
      fibroblasts infected with either wild-type or UL18 knockout CMV virus, and by
      using cell lines transfected with the UL18 gene. In both systems, the expression
      of UL18 resulted in the enhanced killing of target cells. We also show that the
      enhanced killing is due to both UL18-dependent and -independent mechanisms, and
      that the killer cell inhibitory receptors (KIRs) and CD94/NKG2A inhibitory
      receptors for MHC class I do not play a role in affecting susceptibility of CMV
      infected fibroblasts to NK cell-mediated cytotoxicity.

PMID- 9584147
TI  - Factors secreted by human T lymphotropic virus type I (HTLV-I)-infected cells can
      enhance or inhibit replication of HIV-1 in HTLV-I-uninfected cells: implications
      for in vivo coinfection with HTLV-I and HIV-1.
AB  - It remains controversial whether human T lymphotropic virus type I (HTLV-I)
      coinfection leads to more rapid progression of human immunodeficiency virus (HIV)
      disease in dually infected individuals. To investigate whether HTLV-I infection
      of certain cells can modulate HIV-1 infection of surrounding cells, primary
      CD4(+) T cells were treated with cell-free supernatants from HTLV-I-infected MT-2
      cell cultures. The primary CD4+ T cells became resistant to macrophage (M)-tropic
      HIV-1 but highly susceptible to T cell (T)-tropic HIV-1. The CC chemokines RANTES
      (regulated on activation, normal T cell expressed and secreted), macrophage
      inflammatory protein (MIP)-1alpha, and MIP-1beta in the MT-2 cell supernatants
      were identified as the major suppressive factors for M-tropic HIV-1 as well as
      the enhancers of T-tropic HIV-1 infection, whereas soluble Tax protein increased
      susceptibility to both M- and T-tropic HIV-1. The effect of Tax or CC chemokines
      on T-tropic HIV-1 was mediated, at least in part, by increasing HIV Env-mediated
      fusogenicity. Our data suggest that the net effect of HTLV-I coinfection in HIV
      infected individuals favors the transition from M- to T-tropic HIV phenotype,
      which is generally indicative of progressive HIV disease.

PMID- 9584148
TI  - Dissociation of intracellular signaling pathways in response to partial agonist
      ligands of the T cell receptor.
AB  - The T cell receptor (TCR) is a versatile receptor able to generate different
      signals that result in distinct T cell responses. The pattern of early signals is
      determined by the TCR binding kinetics that control the ability of the ligand to
      coengage TCR and coreceptor. Coengagement of TCR and CD4 results in an agonist
      signaling pattern with complete tyrosine phosphorylation of TCR subunits, and
      recruitment and activation of ZAP-70. In contrast, TCR engagement without CD4
      coengagement causes a partial agonist type of signaling, characterized by
      distinct phosphorylation of TCR subunits and recruitment but no activation of ZAP
      70. The pathways triggered by partial agonist signaling are unknown. Here, we
      show that agonists cause association of active lck and active ZAP-70 with p120
      GTPase-activating protein (p120-GAP). These associations follow engagement of CD4
      or CD3, respectively. In contrast, partial agonists do not activate lck or ZAP
      70, but induce association of p120-GAP with inactive ZAP-70. Despite these
      differences, both agonist and partial agonist signals activate the mitogen
      activated protein kinase (MAPK) pathway. However, MAPK activation by partial
      agonists is transient, supporting a kinetic, CD4-dependent model for the
      mechanism of action of variant TCR ligands. Transient MAPK activation may explain
      some of the responses to TCR partial agonists and antagonists.

PMID- 9584149
TI  - H2-M3 restricted presentation of a Listeria-derived leader peptide.
AB  - Protective immunity to infection by many intracellular pathogens requires
      recognition by cytotoxic T lymphocytes (CTLs) of antigens presented on major
      histocompatibility complex (MHC) class I molecules. To be presented for
      recognition by pathogen-specific CTLs, these antigens must gain access to the
      host cell class I processing pathway. In the case of intracellular bacterial
      pathogens, the majority of bacterial proteins are retained within the bacterial
      membrane and therefore remain inaccessible to the host cell for antigen
      processing. We have isolated a CTL clone from a C57BL/6 mouse infected with the
      intracellular gram-positive bacterium Listeria monocytogenes (LM) and have
      identified the source of the antigen. Using a genomic expression library, we
      determined that the clone recognizes an antigenic N-formyl peptide presented by
      the nonpolymorphic murine MHC class Ib molecule, H2-M3. Several lengths of this
      peptide were able to sensitize cells for lysis by this CTL clone. The source of
      this antigenic peptide is a 23-amino acid polypeptide encoded at the start of a
      polycistronic region. Analysis of mRNA secondary structure of this region
      suggests that this polypeptide may be a leader peptide encoded by a
      transcriptional attenuator.

PMID- 9584150
TI  - T cell receptor-initiated calcium release is uncoupled from capacitative calcium
      entry in Itk-deficient T cells.
AB  - Itk, a Tec family tyrosine kinase, plays an important but as yet undefined role
      in T cell receptor (TCR) signaling. Here we show that T cells from Itk-deficient
      mice have a TCR-proximal signaling defect, resulting in defective interleukin 2
      secretion. Upon TCR stimulation, Itk-/- T cells release normal amounts of calcium
      from intracellular stores, but fail to open plasma membrane calcium channels.
      Since thapsigargin-induced store depletion triggers normal calcium entry in Itk-/
      T cells, an impaired biochemical link between store depletion and channel
      opening is unlikely to be responsible for this defect. Biochemical studies
      indicate that TCR-induced inositol 1,4,5 tris-phosphate (IP3) generation and
      phospholipase C gamma1 tyrosine phosphorylation are substantially reduced in Itk
      /- T cells. In contrast, TCR-zeta and ZAP-70 are phosphorylated normally,
      suggesting that Itk functions downstream of, or in parallel to, ZAP-70 to
      facilitate TCR-induced IP3 production. These findings support a model in which
      quantitative differences in cytosolic IP3 trigger distinct responses, and in
      which only high concentrations of IP3 trigger the influx of extracellular
      calcium.

PMID- 9584151
TI  - An RNA splicing enhancer-like sequence is a component of a splicing inhibitor
      element from Rous sarcoma virus.
AB  - The accumulation in infected cells of large amounts of unspliced viral RNA for
      use as mRNA and genomic RNA is a hallmark of retrovirus replication. The negative
      regulator of splicing (NRS) is a long cis-acting RNA element in Rous sarcoma
      virus that contributes to unspliced RNA accumulation through splicing inhibition.
      One of two critical sequences located in the NRS 3' region resembles a minor
      class 5' splice site and is required for U11 small nuclear ribonucleoprotein
      (snRNP) binding to the NRS. The second is a purine-rich region in the 5' half
      that interacts with the splicing factor SF2/ASF. In this study we investigated
      the possibility that this purine-rich region provides an RNA splicing enhancer
      function required for splicing inhibition. In vitro, the NRS acted as a potent,
      orientation-dependent enhancer of Drosophila doublesex pre-mRNA splicing, and
      enhancer activity mapped to the purine-rich domain. Analysis of a number of site
      directed and deletion mutants indicated that enhancer activity was diffusely
      located throughout a 60-nucleotide area but only the activity associated with a
      short region previously shown to bind SF2/ASF correlated with efficient splicing
      inhibition. The significance of the enhancer activity to splicing inhibition was
      demonstrated by using chimeras in which two authentic enhancers (ASLV and FP)
      were substituted for the native NRS purine region. In each case, splicing
      inhibition in transfected cells was restored to levels approaching that observed
      for the NRS. The observation that a nonfunctional version of the FP enhancer
      (FPD) that does not bind SF2/ASF also fails to block splicing when paired with
      the NRS 3' region supports the notion that SF2/ASF binding to the NRS is
      relevant, but other SR proteins may substitute if an appropriate binding site is
      supplied. Our results are consistent with a role for the purine region in
      facilitated snRNP binding to the NRS via SF2/ASF.

PMID- 9584152
TI  - Translation of vascular endothelial growth factor mRNA by internal ribosome
      entry: implications for translation under hypoxia.
AB  - Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic
      growth factor that promotes compensatory angiogenesis in circumstances of oxygen
      shortage. The requirement for translational regulation of VEGF is imposed by the
      cumbersome structure of the 5' untranslated region (5'UTR), which is incompatible
      with efficient translation by ribosomal scanning, and by the physiologic
      requirement for maximal VEGF production under conditions of hypoxia, where
      overall protein synthesis is compromised. Using bicistronic reporter gene
      constructs, we show that the 1,014-bp 5'UTR of VEGF contains a functional
      internal ribosome entry site (IRES). Efficient cap-independent translation is
      maintained under hypoxia, thereby securing efficient production of VEGF even
      under unfavorable stress conditions. To identify sequences within the 5'UTR
      required for maximal IRES activity, deletion mutants were analyzed. Elimination
      of the majority (851 nucleotides) of internal 5'UTR sequences not only maintained
      full IRES activity but also generated a significantly more potent IRES. Activity
      of the 163-bp long "improved" IRES element was abrogated, however, following
      substitution of a few bases near the 5' terminus as well as substitutions close
      to the translation start codon. Both the full-length 5'UTR and its truncated
      version function as translational enhancers in the context of a monocistronic
      mRNA.

PMID- 9584153
TI  - The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates
      with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic
      factor gene expression.
AB  - Specification and differentiation of the cardiac muscle lineage appear to require
      a combinatorial network of many factors. The cardiac muscle-restricted homeobox
      protein Csx/Nkx2.5 (Csx) is expressed in the precardiac mesoderm as well as the
      embryonic and adult heart. Targeted disruption of Csx causes embryonic lethality
      due to abnormal heart morphogenesis. The zinc finger transcription factor GATA4
      is also expressed in the heart and has been shown to be essential for heart tube
      formation. GATA4 is known to activate many cardiac tissue-restricted genes. In
      this study, we tested whether Csx and GATA4 physically associate and
      cooperatively activate transcription of a target gene. Coimmunoprecipitation
      experiments demonstrate that Csx and GATA4 associate intracellularly.
      Interestingly, in vitro protein-protein interaction studies indicate that helix
      III of the homeodomain of Csx is required to interact with GATA4 and that the
      carboxy-terminal zinc finger of GATA4 is necessary to associate with Csx. Both
      regions are known to directly contact the cognate DNA sequences. The promoter
      enhancer region of the atrial natriuretic factor (ANF) contains several putative
      Csx binding sites and consensus GATA4 binding sites. Transient-transfection
      assays indicate that Csx can activate ANF reporter gene expression to the same
      extent that GATA4 does in a DNA binding site-dependent manner. Coexpression of
      Csx and GATA4 synergistically activates ANF reporter gene expression. Mutational
      analyses suggest that this synergy requires both factors to fully retain their
      transcriptional activities, including the cofactor binding activity. These
      results demonstrate the first example of homeoprotein and zinc finger protein
      interaction in vertebrates to cooperatively regulate target gene expression. Such
      synergistic interaction among tissue-restricted transcription factors may be an
      important mechanism to reinforce tissue-specific developmental pathways.

PMID- 9584154
TI  - Characterization of ABF-1, a novel basic helix-loop-helix transcription factor
      expressed in activated B lymphocytes.
AB  - Proteins of the basic helix-loop-helix (bHLH) family are required for a number of
      different developmental pathways, including neurogenesis, lymphopoiesis,
      myogenesis, and sex determination. Using a yeast two-hybrid screen, we have
      identified a new bHLH transcription factor, ABF-1, from a human B-cell cDNA
      library. Within the bHLH region, ABF-1 shows a remarkable conservation with other
      HLH proteins, including tal-1, NeuroD, and paraxis. Its expression pattern is
      restricted to a subset of lymphoid tissues, Epstein-Barr virus (EBV)-transformed
      lymphoblastoid cell lines, and activated human B cells. ABF-1 is capable of
      binding an E-box element either as a homodimer or as a heterodimer with E2A.
      Furthermore, a heterodimeric complex containing ABF-1 and E2A can be detected in
      EBV-immortalized lymphoblastoid cell lines. ABF-1 contains a transcriptional
      repression domain and is capable of inhibiting the transactivation capability of
      E47 in mammalian cells. ABF-1 represents the first example of a B-cell-restricted
      bHLH protein, and its expression pattern suggests that ABF-1 may play a role in
      regulating antigen-dependent B-cell differentiation.

PMID- 9584155
TI  - Mechanism responsible for T-cell antigen receptor- and CD28- or interleukin 1 (IL
      1) receptor-initiated regulation of IL-2 gene expression by NF-kappaB.
AB  - Initiation of the T-helper lymphocyte activation program is regulated through the
      T-cell receptor (TCR) and costimulatory receptors. Analysis of TCR and either
      anti-CD28- or interleukin 1 (IL-1)-mediated activation of the IL-2 promoter shows
      that costimulatory signals augment promoter activity through NF-kappaB sites.
      This study comparatively evaluates the mechanisms whereby signals initiated from
      the TCR and these two costimulatory receptors converge to synergistically
      increase NF-kappaB transcriptional activity. IL-1 alone stimulates an acute but
      transient NF-kappaB nuclear localization and a suboptimal NF-kappaB
      transcriptional response. In contrast, anti-CD3-anti-CD28 or anti-CD3-IL-1
      synergistically stimulate prolonged NF-kappaB nuclear localization and NF-kappaB
      mediated transcription. Both TCR- and costimulatory receptor-initiated
      synergistic NF-kappaB responses result from prolonging high rates of cytosolic
      IkappaB degradation during the second phase of the biphasic NF-kappaB nuclear
      localization. However, in contrast to previous reports, prolonged nuclear
      localization of NF-kappaB complexes is not necessarily associated with long-term
      depletion of IkappaBbeta. In response to either costimulus, c-Rel selectively
      translocated to the nucleus as a result of induced c-Rel expression and the
      continued production of c-Rel-IkappaBalpha complexes, which turn over rapidly due
      to the high rate of IkappaBalpha degradation in the cytosol during the second
      phase of the response. In contrast, IkappaBbeta is nearly completely degraded
      during the acute response to either IL-1 or anti-CD3-IL-1 while anti-CD3-anti
      CD28 stimulates only a partial reduction (35 to 40%) in cytosolic IkappaBbeta.
      Cyclosporine (CsA), which inhibits stimulus-induced NF-kappaB transcriptional
      activity, selectively inhibits the stimulus-induced c-Rel nuclear localization
      and the rapid formation and degradation of c-Rel-IkappaBalpha complexes in the
      cytosol. CsA also inhibits both the prolonged, high rate of IkappaBalpha
      degradation and the lower level of IkappaBbeta turnover during the second phase
      of the activation response. Together, these results suggest a mechanism by which
      signals from the T-cell antigen receptor and either CD28 or IL-1 synergistically
      regulate IL-2 gene transcription by modulating NF-kappaB nuclear translocation.

PMID- 9584156
TI  - The regulatory particle of the Saccharomyces cerevisiae proteasome.
AB  - The proteasome is a multisubunit protease responsible for degrading proteins
      conjugated to ubiquitin. The 670-kDa core particle of the proteasome contains the
      proteolytic active sites, which face an interior chamber within the particle and
      are thus protected from the cytoplasm. The entry of substrates into this chamber
      is thought to be governed by the regulatory particle of the proteasome, which
      covers the presumed channels leading into the interior of the core particle. We
      have resolved native yeast proteasomes into two electrophoretic variants and have
      shown that these represent core particles capped with one or two regulatory
      particles. To determine the subunit composition of the regulatory particle, yeast
      proteasomes were purified and analyzed by gradient sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Resolution of the individual polypeptides
      revealed 17 distinct proteins, whose identities were determined by amino acid
      sequence analysis. Six of the subunits have sequence features of ATPases (Rpt1 to
      Rpt6). Affinity chromatography was used to purify regulatory particles from
      various strains, each of which expressed one of the ATPases tagged with
      hexahistidine. In all cases, multiple untagged ATPases copurified, indicating
      that the ATPases assembled together into a heteromeric complex. Of the remaining
      11 subunits that we have identified (Rpn1 to Rpn3 and Rpn5 to Rpn12), 8 are
      encoded by previously described genes and 3 are encoded by genes not previously
      characterized for yeasts. One of the previously unidentified subunits exhibits
      limited sequence similarity with deubiquitinating enzymes. Overall, regulatory
      particles from yeasts and mammals are remarkably similar, suggesting that the
      specific mechanistic features of the proteasome have been closely conserved over
      the course of evolution.

PMID- 9584157
TI  - Increased expression of cyclin D2 during multiple states of growth arrest in
      primary and established cells.
AB  - Cyclin D2 is a member of the family of D-type cyclins that is implicated in cell
      cycle regulation, differentiation, and oncogenic transformation. To better
      understand the role of this cyclin in the control of cell proliferation, cyclin
      D2 expression was monitored under various growth conditions in primary human and
      established murine fibroblasts. In different states of cellular growth arrest
      initiated by contact inhibition, serum starvation, or cellular senescence, marked
      increases (5- to 20-fold) were seen in the expression levels of cyclin D2 mRNA
      and protein. Indirect immunofluorescence studies showed that cyclin D2 protein
      localized to the nucleus in G0, suggesting a nuclear function for cyclin D2 in
      quiescent cells. Cyclin D2 was also found to be associated with the cyclin
      dependent kinases CDK2 and CDK4 but not CDK6 during growth arrest. Cyclin D2-CDK2
      complexes increased in amounts but were inactive as histone H1 kinases in
      quiescent cells. Transient transfection and needle microinjection of cyclin D2
      expression constructs demonstrated that overexpression of cyclin D2 protein
      efficiently inhibited cell cycle progression and DNA synthesis. These data
      suggest that in addition to a role in promoting cell cycle progression through
      phosphorylation of retinoblastoma family proteins in some cell systems, cyclin D2
      may contribute to the induction and/or maintenance of a nonproliferative state,
      possibly through sequestration of the CDK2 catalytic subunit.

PMID- 9584158
TI  - Role of the negative charges in the cytosolic domain of TOM22 in the import of
      precursor proteins into mitochondria.
AB  - TOM22 is an essential mitochondrial outer membrane protein required for the
      import of precursor proteins into the organelles. The amino-terminal 84 amino
      acids of TOM22 extend into the cytosol and include 19 negatively and 6 positively
      charged residues. This region of the protein is thought to interact with
      positively charged presequences on mitochondrial preproteins, presumably via
      electrostatic interactions. We constructed a series of mutant derivatives of
      TOM22 in which 2 to 15 of the negatively charged residues in the cytosolic domain
      were changed to their corresponding amido forms. The mutant constructs were
      transformed into a sheltered Neurospora crassa heterokaryon bearing a
      tom22::hygromycin R disruption in one nucleus. All constructs restored viability
      to the disruption-carrying nucleus and gave rise to homokaryotic strains
      containing mutant tom22 alleles. Isolated mitochondria from three representative
      mutant strains, including the mutant carrying 15 neutralized residues (strain
      861), imported precursor proteins at efficiencies comparable to those for wild
      type organelles. Precursor binding studies with mitochondrial outer membrane
      vesicles from several of the mutant strains, including strain 861, revealed only
      slight differences from binding to wild-type vesicles. Deletion mutants lacking
      portions of the negatively charged region of TOM22 can also restore viability to
      the disruption-containing nucleus, but mutants lacking the entire region cannot.
      Taken together, these data suggest that an abundance of negative charges in the
      cytosolic domain of TOM22 is not essential for the binding or import of
      mitochondrial precursor proteins; however, other features in the domain are
      required.

PMID- 9584159
TI  - Relationship of the xeroderma pigmentosum group E DNA repair defect to the
      chromatin and DNA binding proteins UV-DDB and replication protein A.
AB  - Cells from complementation groups A through G of the heritable sun-sensitive
      disorder xeroderma pigmentosum (XP) show defects in nucleotide excision repair of
      damaged DNA. Proteins representing groups A, B, C, D, F, and G are subunits of
      the core recognition and incision machinery of repair. XP group E (XP-E) is the
      mildest form of the disorder, and cells generally show about 50% of the normal
      repair level. We investigated two protein factors previously implicated in the XP
      E defect, UV-damaged DNA binding protein (UV-DDB) and replication protein A
      (RPA). Three newly identified XP-E cell lines (XP23PV, XP25PV, and a line
      formerly classified as an XP variant) were defective in UV-DDB binding activity
      but had levels of RPA in the normal range. The XP-E cell extracts did not display
      a significant nucleotide excision repair defect in vitro, with either UV
      irradiated DNA or a uniquely placed cisplatin lesion used as a substrate.
      Purified UV-DDB protein did not stimulate repair of naked DNA by DDB- XP-E cell
      extracts, but microinjection of the protein into DDB- XP-E cells could partially
      correct the repair defect. RPA stimulated repair in normal, XP-E, or complemented
      extracts from other XP groups, and so the effect of RPA was not specific for XP-E
      cell extracts. These data strengthen the connection between XP-E and UV-DDB.
      Coupled with previous results, the findings suggest that UV-DDB has a role in the
      repair of DNA in chromatin.

PMID- 9584160
TI  - A chimeric subunit of yeast transcription factor IIIC forms a subcomplex with
      tau95.
AB  - The multisubunit yeast transcription factor IIIC (TFIIIC) is a multifunctional
      protein required for promoter recognition, transcription factor IIIB recruitment,
      and chromatin antirepression. We report the isolation and characterization of
      TFC7, an essential gene encoding the 55-kDa polypeptide, tau55, present in
      affinity-purified TFIIIC. tau55 is a chimeric protein generated by an ancient
      chromosomal rearrangement. Its C-terminal half is essential for cell viability
      and sufficient to ensure TFIIIC function in DNA binding and transcription assays.
      The N-terminal half is nonessential and highly similar to a putative yeast
      protein encoded on another chromosome and to a cyanobacterial protein of unknown
      function. Partial deletions of the N-terminal domain impaired tau55 function at a
      high temperature or in media containing glycerol or ethanol, suggesting a link
      between PolIII transcription and metabolic pathways. Interestingly, tau55 was
      found, together with TFIIIC subunit tau95, in a protein complex which was
      distinct from TFIIIC and which may play a role in the regulation of PolIII
      transcription, possibly in relation to cell metabolism.

PMID- 9584161
TI  - 5' processing of tRNA precursors can Be modulated by the human La antigen
      phosphoprotein.
AB  - Eukaryotic precursor (pre)-tRNAs are processed at both ends prior to maturation.
      Pre-tRNAs and other nascent transcripts synthesized by RNA polymerase III are
      bound at their 3' ends at the sequence motif UUUOH [3' oligo(U)] by the La
      antigen, a conserved phosphoprotein whose role in RNA processing has been
      associated previously with 3'-end maturation only. We show that in addition to
      its role in tRNA 3'-end maturation, human La protein can also modulate 5'
      processing of pre-tRNAs. Both the La antigen's N-terminal RNA-binding domain and
      its C-terminal basic region are required for attenuation of pre-tRNA 5'
      processing. RNA binding and nuclease protection assays with a variety of pre-tRNA
      substrates and mutant La proteins indicate that 5' protection is a highly
      selective activity of La. This activity is dependent on 3' oligo(U) in the pre
      tRNA for interaction with the N-terminal RNA binding domain of La and interaction
      of the C-terminal basic region of La with the 5' triphosphate end of nascent pre
      tRNA. Phosphorylation of La is known to occur on serine 366, adjacent to the C
      terminal basic region. We show that this modification interferes with the La
      antigen's ability to protect pre-tRNAiMet from 5' processing either by HeLa
      extract or purified RNase P but that it does not affect interaction with the 3'
      end of pre-tRNA. These findings provide the first evidence to indicate that tRNA
      5'-end maturation may be regulated in eukaryotes. Implications of triphosphate
      recognition is discussed as is a role for La phosphoprotein in controlling
      transcriptional and posttranscriptional events in the biogenesis of polymerase
      III transcripts.

PMID- 9584162
TI  - Inhibition of cyclin D1 kinase activity is associated with E2F-mediated
      inhibition of cyclin D1 promoter activity through E2F and Sp1.
AB  - Coordinated interactions between cyclin-dependent kinases (Cdks), their target
      "pocket proteins" (the retinoblastoma protein [pRB], p107, and p130), the pocket
      protein binding E2F-DP complexes, and the Cdk inhibitors regulate orderly cell
      cycle progression. The cyclin D1 gene encodes a regulatory subunit of the Cdk
      holoenzymes, which phosphorylate the tumor suppressor pRB, leading to the release
      of free E2F-1. Overexpression of E2F-1 can induce apoptosis and may either
      promote or inhibit cellular proliferation, depending upon the cell type. In these
      studies overexpression of E2F-1 inhibited cyclin D1-dependent kinase activity,
      cyclin D1 protein levels, and promoter activity. The DNA binding domain, the pRB
      pocket binding region, and the amino-terminal Sp1 binding domain of E2F-1 were
      required for full repression of cyclin D1. Overexpression of pRB activated the
      cyclin D1 promoter, and a dominant interfering pRB mutant was defective in cyclin
      D1 promoter activation. Two regions of the cyclin D1 promoter were required for
      full E2F-1-dependent repression. The region proximal to the transcription
      initiation site at -127 bound Sp1, Sp3, and Sp4, and the distal region at -143
      bound E2F-4-DP-1-p107. In contrast with E2F-1, E2F-4 induced cyclin D1 promoter
      activity. Differential regulation of the cyclin D1 promoter by E2F-1 and E2F-4
      suggests that E2Fs may serve distinguishable functions during cell cycle
      progression. Inhibition of cyclin D1 abundance by E2F-1 may contribute to an
      autoregulatory feedback loop to reduce pRB phosphorylation and E2F-1 levels in
      the cell.

PMID- 9584163
TI  - Cooperation among multiple transcription factors is required for access to
      minimal T-cell receptor alpha-enhancer chromatin in vivo.
AB  - To understand the molecular basis for the dramatic functional synergy between
      transcription factors that bind to the minimal T-cell receptor alpha enhancer
      (Ealpha), we analyzed enhancer occupancy in thymocytes of transgenic mice in vivo
      by genomic footprinting. We found that the formation of a multiprotein complex on
      this enhancer in vivo results from the occupancy of previously identified sites
      for CREB/ATF, TCF/LEF, CBF/PEBP2, and Ets factors as well as from the occupancy
      of two new sites 5' of the CRE site, GC-I (which binds Sp1 in vitro) and GC-II.
      Significantly, although all sites are occupied on a wild-type Ealpha, all sites
      are unoccupied on versions of Ealpha with mutations in the TCF/LEF or Ets sites.
      Previous in vitro experiments demonstrated hierarchical enhancer occupancy with
      independent binding of LEF-1 and CREB. Our data indicate that the formation of a
      multiprotein complex on the enhancer in vivo is highly cooperative and that no
      single Ealpha binding factor can access chromatin in vivo to play a unique
      initiating role in its assembly. Rather, the simultaneous availability of
      multiple enhancer binding proteins is required for chromatin disruption and
      stable binding site occupancy as well as the activation of transcription and
      V(D)J recombination.

PMID- 9584164
TI  - Involvement of TFIID and USA components in transcriptional activation of the
      human immunodeficiency virus promoter by NF-kappaB and Sp1.
AB  - The purified Rel/NF-kappaB (p50/p65) complex and Sp1 markedly activate
      transcription from the human immunodeficiency virus type 1 (HIV-1) promoter in a
      highly purified HeLa reconstituted transcription system. Transcriptional
      activation by NF-kappaB and Sp1 requires both TFIID and the USA fraction. The USA
      derived coactivators PC2 and PC4 fully reconstitute the USA coactivator activity,
      both by repressing the basal level of transcription and by potentiating activator
      function to yield large increases in the levels of transcription induction. Under
      limiting concentrations, PC2 and PC4 also show synergistic effects. The C
      terminal portion (amino acids 416 to 550) of the p65 subunit of NF-kappaB is a
      potent activator when assayed as a Gal fusion in the reconstituted transcription
      system and interacts both with TATA-binding protein (TBP) and with several human
      TBP-associated factors (TAFs) that include TAFII250. The p65 activation domain
      mediates transcription activation in the presence of partially reconstituted
      TFIID species that include a minimal complex containing only TBP and TAFII250.
      These studies also show that, like USA components, TAFs can serve both to repress
      TBP-mediated transcription and, following activator interactions, to reverse the
      repression and effect a net increase in activity. Taken together, these data
      underscore the importance of both TAFs and specific USA-derived coactivators for
      optimal activation of the HIV-1 promoter, as well as certain parallels in their
      overall mechanisms of action.

PMID- 9584165
TI  - RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G
      proteins, inhibits activity of src tyrosine kinases and growth of NIH 3T3 cells.
AB  - To isolate and characterize proteins that interact with the unique domain and SH3
      and SH2 domains of Src and potentially regulate Src activity, we used the yeast
      two-hybrid assay to screen a human lung fibroblast cDNA library. We identified
      RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G
      proteins, as a Src-binding protein. Using GST-Src fusion proteins, we determined
      that RACK1 binds to the SH2 domain of Src. Coimmunoprecipitation of Src and RACK1
      was demonstrated with NIH 3T3 cells. Purified GST-RACK1 inhibited the in vitro
      kinase activity of Src in a concentration-dependent manner. GST-RACK1 (2 microM)
      inhibited the activities of purified Src and Lck tyrosine kinases by 40 to 50%
      but did not inhibit the activities of three serine/threonine kinases that we
      tested. Tyrosine phosphorylation on many cellular proteins decreased in 293T
      cells that transiently overexpressed RACK1. Src activity and cell growth rates
      decreased by 40 to 50% in NIH 3T3 cells that stably overexpressed RACK1. Flow
      cytometric analyses revealed that RACK1-overexpressing cells do not show an
      increased rate of necrosis or apoptosis but do spend significantly more time in
      G0/G1 than do wild-type cells. Prolongation of G0/G1 could account for the
      increased doubling time of RACK1-overexpressing cells. We suggest that RACK1
      exerts its effect on the NIH 3T3 cell cycle in part by inhibiting Src activity.

PMID- 9584166
TI  - Basal extracellular signal-regulated kinase activity modulates cell-cell and cell
      matrix interactions.
AB  - Suppression of the basal extracellular signal-regulated kinase (ERK) activity in
      PC12 cells markedly altered their phenotype. Wild-type cells grew in a
      dissociated pattern adherent to the substrate. The stable expression of an ERK
      inhibitory mutant resulted in the formation of calcium-dependent aggregates which
      were less adherent to the substrate. Concomitantly, the cells reorganized their
      actin cytoskeleton and increased their expression of several adherens junction
      proteins, particularly cadherin. Metabolic labeling demonstrated an increased
      synthesis of cadherin and beta-catenin in these cells. Nontransfected PC12 cells
      and a ras-transformed MDCK cell line also formed aggregates and increased their
      expression of adherens junction proteins following treatment with the selective
      MEK inhibitor PD98059. A peptide containing the HAV cadherin recognition sequence
      attenuated the aggregation. These studies suggest that in PC12 and epithelial
      cells, ERKs are pivotally positioned to enhance substrate interactions when
      active or to release homotypic interactions when suppressed.

PMID- 9584167
TI  - Identification of primary initiation sites for DNA replication in the hamster
      dihydrofolate reductase gene initiation zone.
AB  - Mammalian replication origins appear paradoxical. While some studies conclude
      that initiation occurs bidirectionally from specific loci, others conclude that
      initiation occurs at many sites distributed throughout large DNA regions. To
      clarify this issue, the relative number of early replication bubbles was
      determined at 26 sites in a 110-kb locus containing the dihydrofolate reductase
      (DHFR)-encoding gene in CHO cells; 19 sites were located within an 11-kb sequence
      containing ori-beta. The ratio of approximately 0.8-kb nascent DNA strands to
      nonreplicated DNA at each site was quantified by competitive PCR. Nascent DNA was
      defined either as DNA that was labeled by incorporation of bromodeoxyuridine in
      vivo or as RNA-primed DNA that was resistant to lambda-exonuclease. Two primary
      initiation sites were identified within the 12-kb region, where two-dimensional
      gel electrophoresis previously detected a high frequency of replication bubbles.
      A sharp peak of nascent DNA occurred at the ori-beta origin of bidirectional
      replication where initiation events were 12 times more frequent than at distal
      sequences. A second peak occurred 5 kb downstream at a previously unrecognized
      origin (ori-beta'). Thus, the DHFR gene initiation zone contains at least three
      primary initiation sites (ori-beta, ori-beta', and ori-gamma), suggesting that
      initiation zones in mammals, like those in fission yeast, consist of multiple
      replication origins.

PMID- 9584168
TI  - GATA-1 dominantly activates a program of erythroid gene expression in factor
      dependent myeloid FDCW2 cells.
AB  - Erythrocyte development has previously been shown to depend upon the expression
      of the lineage-restricted trans-acting factor GATA-1. Despite predicted roles for
      this factor during early development, GATA-1-deficient cells in chimeric mice and
      embryonic stem cell cultures mature to a late proerythroblast stage and express
      at least certain genes that normally are thought to be regulated by GATA-1
      (including erythroid Kruppel-like factor [EKLF] and the erythropoietin [Epo]
      receptor). Opportunities to test roles for GATA-1 in erythroid gene activation in
      these systems therefore are limited. In the present study, in an alternate
      approach to test the function of GATA-1, GATA-1 has been expressed together with
      the Epo receptor in myeloid FDCW2 cells and the resulting effects on cytokine
      dependent proliferation and erythroid gene expression have been assessed. GATA-1
      expression at low levels delayed FDCW2ER cell cycle progression at the G1 phase
      specifically during Epo-induced mitogenesis. Upon expression of GATA-1 at
      increased levels, proliferation in response to Epo, interleukin-3 (IL-3), and
      stem cell factor was attenuated and endogenous GATA-1, EKLF and betamaj-globin
      gene expression was activated. Friend of GATA-1 (FOG) transcript levels also were
      enhanced, and ets-1 and c-mpl but not Epo receptor gene expression was induced.
      Finally, in FDCW2 cells expressing increased levels of GATA-1 and a carboxyl
      terminally truncated Epo receptor, Epo (with respect to IL-3 as a control) was
      shown to markedly promote globin transcript expression. Thus, novel evidence for
      select hierarchical roles for GATA-1 and Epo in erythroid lineage specification
      is provided.

PMID- 9584169
TI  - Cyclin partners determine Pho85 protein kinase substrate specificity in vitro and
      in vivo: control of glycogen biosynthesis by Pcl8 and Pcl10.
AB  - In Saccharomyces cerevisiae, PHO85 encodes a cyclin-dependent protein kinase
      (Cdk) with multiple roles in cell cycle and metabolic controls. In association
      with the cyclin Pho80, Pho85 controls acid phosphatase gene expression through
      phosphorylation of the transcription factor Pho4. Pho85 has also been implicated
      as a kinase that phosphorylates and negatively regulates glycogen synthase
      (Gsy2), and deletion of PHO85 causes glycogen overaccumulation. We report that
      the Pcl8/Pcl10 subgroup of cyclins directs Pho85 to phosphorylate glycogen
      synthase both in vivo and in vitro. Disruption of PCL8 and PCL10 caused
      hyperaccumulation of glycogen, activation of glycogen synthase, and a reduction
      in glycogen synthase kinase activity in vivo. However, unlike pho85 mutants, pcl8
      pcl10 cells had normal morphologies, grew on glycerol, and showed proper
      regulation of acid phosphatase gene expression. In vitro, Pho80-Pho85 complexes
      effectively phosphorylated Pho4 but had much lower activity toward Gsy2. In
      contrast, Pcl10-Pho85 complexes phosphorylated Gsy2 at Ser-654 and Thr-667, two
      physiologically relevant sites, but only poorly phosphorylated Pho4. Thus, both
      the in vitro and in vivo substrate specificity of Pho85 is determined by the
      cyclin partner. Mutation of PHO85 suppressed the glycogen storage deficiency of
      snf1 or glc7-1 mutants in which glycogen synthase is locked in an inactive state.
      Deletion of PCL8 and PCL10 corrected the deficit in glycogen synthase activity in
      both the snf1 and glc7-1 mutants, but glycogen synthesis was restored only in the
      glc7-1 mutant strain. This genetic result suggests an additional role for Pho85
      in the negative regulation of glycogen accumulation that is independent of Pcl8
      and Pcl10.

PMID- 9584170
TI  - Inhibitor of apoptosis proteins physically interact with and block apoptosis
      induced by Drosophila proteins HID and GRIM.
AB  - Reaper (RPR), HID, and GRIM activate apoptosis in cells programmed to die during
      Drosophila development. We have previously shown that transient overexpression of
      RPR in the lepidopteran SF-21 cell line induces apoptosis and that members of the
      inhibitor of apoptosis (IAP) family of antiapoptotic proteins can inhibit RPR
      induced apoptosis and physically interact with RPR through their BIR motifs (D.
      Vucic, W. J. Kaiser, A. J. Harvey, and L. K. Miller, Proc. Natl. Acad. Sci. USA
      94:10183-10188, 1997). In this study, we found that transient overexpression of
      HID and GRIM also induced apoptosis in the SF-21 cell line. Baculovirus and
      Drosophila IAPs blocked HID- and GRIM-induced apoptosis and also physically
      interacted with them through the BIR motifs of the IAPs. The region of sequence
      similarity shared by RPR, HID, and GRIM, the N-terminal 14 amino acids of each
      protein, was required for the induction of apoptosis by HID and its binding to
      IAPs. When stably overexpressed by fusion to an unrelated, nonapoptotic
      polypeptide, the N-terminal 37 amino acids of HID and GRIM were sufficient to
      induce apoptosis and confer IAP binding activity. However, GRIM was more complex
      than HID since the C-terminal 124 amino acids of GRIM retained apoptosis-inducing
      and IAP binding activity, suggesting the presence of two independent apoptotic
      motifs within GRIM. Coexpression of IAPs with HID stabilized HID levels and
      resulted in the accumulation of HID in punctate perinuclear locations which
      coincided with IAP localization. The physical interaction of IAPs with RPR, HID,
      and GRIM provides a common molecular mechanism for IAP inhibition of these
      Drosophila proapoptotic proteins.

PMID- 9584171
TI  - TFII-I enhances activation of the c-fos promoter through interactions with
      upstream elements.
AB  - The transcription factor TFII-I was initially isolated as a factor that can bind
      to initiator elements in core promoters. Recent evidence suggests that TFII-I may
      also have a role in signal transduction. We have found that overexpression of
      TFII-I can enhance the response of the wild-type c-fos promoter to a variety of
      stimuli. This effect depends on the c-fos c-sis-platelet-derived growth factor
      inducible factor binding element (SIE) and serum response element (SRE). There is
      no effect of cotransfected TFII-I on the TATA box containing the c-fos basal
      promoter. Three TFII-I binding sites can be found in c-fos promoter. Two of these
      overlap the c-fos SIE and SRE, and another is located just upstream of the TATA
      box. Mutations that distinguish between serum response factor (SRF), STAT, and
      TFII-I binding to the c-fos SIE and SRE suggest that the binding of TFII-I to
      these elements is important for c-fos induction in conjunction with the SRF and
      STAT transcription factors. Moreover, TFII-I can form in vivo protein-protein
      complexes with the c-fos upstream activators SRF, STAT1, and STAT3. These results
      suggest that TFII-I may mediate the functional interdependence of the c-fos SIE
      and SRE elements. In addition, the ras pathway is required for TFII-I to exert
      its effects on the c-fos promoter, and growth factor stimulation enhances
      tyrosine phosphorylation of TFII-I. These results indicate that TFII-I is
      involved in signal transduction as well as transcriptional activation of the c
      fos promoter.

PMID- 9584172
TI  - Mutations in the extracellular domain cause RET loss of function by a dominant
      negative mechanism.
AB  - The RET proto-oncogene encodes a tyrosine kinase receptor expressed in
      neuroectoderm-derived cells. Mutations in specific regions of the gene are
      responsible for the tumor syndromes multiple endocrine neoplasia types 2A and 2B
      (MEN 2A and 2B), while mutations along the entire gene are involved in a
      developmental disorder of the gastrointestinal tract, Hirschsprung's disease
      (HSCR disease). Two mutants in the extracellular domain of RET, one associated
      with HSCR disease and one carrying a flag epitope, were analyzed to investigate
      the impact of the mutations on RET function. Both mutants were impeded in their
      maturation, resulting in the lack of the 170-kDa mature form and the accumulation
      of the 150-kDa immature form in the endoplasmic reticulum. Although not exposed
      on the cell surface, the 150-kDa species formed dimers and aggregates; this was
      more pronounced in a double mutant bearing a MEN 2A mutation. Tyrosine
      phosphorylation and the transactivation potential were drastically reduced in
      single and double mutants. Finally, in cotransfection experiments both mutants
      exerted a dominant negative effect over protoRET and RET2A through the formation
      of a heteromeric complex that prevents their maturation and function. These
      results suggest that HSCR mutations in the extracellular region cause RET loss of
      function through a dominant negative mechanism.

PMID- 9584173
TI  - Genetic and biochemical analysis of p23 and ansamycin antibiotics in the function
      of Hsp90-dependent signaling proteins.
AB  - The ubiquitous molecular chaperone Hsp90 acts in concert with a cohort of
      associated proteins to facilitate the functional maturation of a number of
      cellular signaling proteins, such as steroid hormone receptors and oncogene
      tyrosine kinases. The Hsp90-associated protein p23 is required for the assembly
      of functional steroid aporeceptor complexes in cell lysates, and Hsp90-binding
      ansamycin antibiotics disrupt the activity of Hsp90-dependent signaling proteins
      in cultured mammalian cells and prevent the association of p23 with Hsp90
      receptor heterocomplexes; these observations have led to the hypotheses that p23
      is required for the maturation of Hsp90 target proteins and that ansamycin
      antibiotics abrogate the activity of such proteins by disrupting the interaction
      of p23 with Hsp90. In this study, I demonstrate that ansamycin antibiotics
      disrupt the function of Hsp90 target proteins expressed in yeast cells; prevent
      the assembly of Sba1, a yeast p23-like protein, into steroid receptor-Hsp90
      complexes; and result in the assembly of receptor-Hsp90 complexes that are
      defective for ligand binding. To assess the role of p23 in Hsp90 target protein
      function, I show that the activity of Hsp90 target proteins is unaffected by
      deletion of SBA1. Interestingly, steroid receptor activity in cells lacking Sba1
      displays increased sensitivity to ansamycin antibiotics, and this phenotype is
      rescued by the expression of human p23 in yeast cells. These findings indicate
      that Hsp90-dependent signaling proteins can achieve a functional conformation in
      vivo in the absence of p23. Furthermore, while the presence of p23 decreases the
      sensitivity of Hsp90-dependent processes to ansamycin treatment, ansamycin
      antibiotics disrupt signaling through some mechanism other than altering the
      Hsp90-p23 interaction.

PMID- 9584174
TI  - Functional replacement of the mouse E2A gene with a human HEB cDNA.
AB  - The mammalian E2A, HEB, and E2-2 genes encode a unique class of basic helix-loop
      helix (bHLH) transcription factors that are evolutionarily conserved and
      essential for embryonic and postnatal development. While the structural and
      functional similarities among the gene products are well demonstrated, it is not
      clear why deletion of E2A, but not HEB or E2-2, leads to a complete arrest in B
      lymphocyte development. To understand the molecular basis of the functional
      specificity between E2A and HEB/E2-2 in mammalian development, we generated and
      tested a panel of E2A knockin mutations including subtle mutations in the E12 and
      E47 exons and substitution of both E12 and E47 exons with a human HEB cDNA. We
      find that the alternatively spliced E12 and E47 bHLH proteins of the E2A gene
      play similar and additive roles in supporting B lymphopoiesis. Further, we find
      that HEB driven by the endogenous E2A promoter can functionally replace E2A in
      supporting B-cell commitment and differentiation toward completion. Finally, the
      postnatal lethality associated with E2A disruption is fully rescued by the
      addition of HEB. This study suggests that the functional divergence among E12,
      E47, and HEB in different cell types is partially defined by the context of gene
      expression.

PMID- 9584175
TI  - Histone- and protamine-DNA association: conservation of different patterns within
      the beta-globin domain in human sperm.
AB  - Most DNA in human sperm is bound to highly basic proteins called protamines, but
      a small proportion is complexed with histones similar to those found in active
      chromatin. This raises the intriguing possibility that histones in sperm are
      marking sets of genes that will be preferentially activated during early
      development. We have examined the chromatin structure of members of the beta
      globin gene family, which are expressed at different times in development, and
      the protamine 2 gene, which is expressed in spermatids prior to the widespread
      displacement of histones by transition proteins. The genes coding for epsilon and
      gamma globin, which are active in the embryonic yolk sac, contain regions which
      are histone associated in the sperm. No histone-associated regions are present at
      the sites tested within the beta- and delta-globin genes which are silent in the
      embryonic yolk sac. The trends of histone or protamine association are consistent
      for samples from the same person, and no significant between-subject variations
      in these trends are found for 13 of the 15 fragments analyzed in the two donors.
      The results suggest that sperm chromatin structures are generally similar in
      different men but that the length of the histone-associated regions can vary. The
      association of sperm DNA with histones or protamines sometimes changes within as
      little as 400 bp of DNA, suggesting that there is fine control over the retention
      of histones.

PMID- 9584176
TI  - Cloning and characterization of a specific receptor for mouse oncostatin M.
AB  - Oncostatin M (OSM) is a member of a family of cytokines that includes ciliary
      neurotrophic factor, interleukin-6, interleukin-11, cardiotrophin-1, and leukemia
      inhibitory factor (LIF). The receptors for these cytokines consist of a common
      signaling subunit, gp130, to which other subunits are added to modify ligand
      specificity. We report here the isolation and characterization of a cDNA encoding
      a subunit of the mouse OSM receptor. In NIH 3T3 cells (which endogenously express
      gp130, LIF receptor beta [LIFRbeta], and the protein product, c12, of the cDNA
      described here), mouse LIF, human LIF, and human OSM signaled through receptors
      containing the LIFRbeta and gp130 but not through the mouse OSM receptor. Mouse
      OSM, however, signaled only through a c12-gp130 complex; it did not use the LIF
      receptor. Binding studies demonstrated that mouse OSM associated directly with
      either the c12 protein or gp130. These data highlight the species-specific
      differences in receptor utilization and signal transduction between mouse and
      human OSM. In mouse cells, only mouse OSM is capable of activating the mouse OSM
      receptor; human OSM instead activates the LIF receptor. Therefore, these data
      suggest that all previous studies with human OSM in mouse systems did not
      elucidate the biology of OSM but, rather, reflected the biological actions of
      LIF.

PMID- 9584177
TI  - A gene-targeting approach identifies a function for the first intron in
      expression of the alpha1(I) collagen gene.
AB  - The role of the first intron of the Col1A1 gene in the regulation of type I
      collagen synthesis remains uncertain and controversial despite numerous studies
      that have made use of transgenic and transfection experiments. To examine the
      importance of the first intron in regulation of the gene, we have used the double
      replacement method of gene targeting to introduce, by homologous recombination in
      embryonic stem (ES) cells, a mutated Col1A1 allele (Col-IntDelta). The Col
      IntDelta allele contains a 1. 3-kb deletion within intron I and is also marked by
      the introduction of a silent mutation that created an XhoI restriction site in
      exon 7. Targeted mice were generated from two independently derived ES cell
      clones. Mice carrying two copies of the mutated gene were born in the expected
      Mendelian ratio, developed normally, and showed no apparent abnormalities. We
      used heterozygous mice to determine whether expression of the mutated allele
      differs from that of the normal allele. For this purpose, we developed a reverse
      transcription-PCR assay which takes advantage of the XhoI polymorphism in exon 7.
      Our results indicate that in the skin, and in cultured cells derived from the
      skin, the intron plays little or no role in constitutive expression of collagen
      I. However, in the lungs of young mice, the mutated allele was expressed at about
      75% of the level of the normal allele, and in the adult lung expression was
      decreased to less than 50%. These results were confirmed by RNase protection
      assays which demonstrated a two- to threefold decrease in Col1A1 mRNA in lungs of
      homozygous mutant mice. Surprisingly, in cultured cells derived from the lung,
      the mutated allele was expressed at a level similar to that of the wild-type
      allele. Our results also indicated an age-dependent requirement for the intact
      intron in expression of the Col1A1 gene in muscle. Since the intron is spliced
      normally, and since the mutant allele is expressed as well as the wild-type
      allele in the skin, reduced mRNA stability is unlikely to contribute to the
      reduction in transcript levels. We conclude that the first intron of the Col1A1
      gene plays a tissue-specific and developmentally regulated role in
      transcriptional regulation of the gene. Our experiments demonstrate the utility
      of gene-targeting techniques that produce subtle mutations for studies of cis
      acting elements in gene regulation.

PMID- 9584178
TI  - Processing of the intron-encoded U18 small nucleolar RNA in the yeast
      Saccharomyces cerevisiae relies on both exo- and endonucleolytic activities.
AB  - Many small nucleolar RNAs (snoRNAs) are encoded within introns of protein
      encoding genes and are released by processing of their host pre-mRNA. We have
      investigated the mechanism of processing of the yeast U18 snoRNA, which is found
      in the intron of the gene coding for translational elongation factor EF-1beta. We
      have focused our analysis on the relationship between splicing of the EF-1beta
      pre-mRNA and production of the mature snoRNA. Mutations inhibiting splicing of
      the EF-1beta pre-mRNA have been shown to produce normal U18 snoRNA levels
      together with the accumulation of intermediates deriving from the pre-mRNA, thus
      indicating that the precursor is an efficient processing substrate. Inhibition of
      5'-->3' exonucleases obtained by insertion of G cassettes or by the use of a rat1
      1 xrn1Delta mutant strain does not impair U18 release. In the Exo- strain, 3'
      cutoff products, diagnostic of an endonuclease-mediated processing pathway, were
      detected. Our data indicate that biosynthesis of the yeast U18 snoRNA relies on
      two different pathways, depending on both exonucleolytic and endonucleolytic
      activities: a major processing pathway based on conversion of the debranched
      intron and a minor one acting by endonucleolytic cleavage of the pre-mRNA.

PMID- 9584179
TI  - A binding site for multiple transcriptional activators in the fushi tarazu
      proximal enhancer is essential for gene expression in vivo.
AB  - The Drosophila homeobox gene fushi tarazu (ftz) is expressed in a highly dynamic
      striped pattern in early embryos. A key regulatory element that controls the ftz
      pattern is the ftz proximal enhancer, which mediates positive autoregulation via
      multiple binding sites for the Ftz protein. In addition, the enhancer is
      necessary for stripe establishment prior to the onset of autoregulation. We
      previously identified nine binding sites for multiple Drosophila nuclear proteins
      in a core 323-bp region of the enhancer. Three of these nine sites interact with
      the same cohort of nuclear proteins in vitro. We showed previously that the
      nuclear receptor Ftz-F1 interacts with this repeated module. Here we purified
      additional proteins interacting with this module from Drosophila nuclear
      extracts. Peptide sequences of the zinc finger protein Ttk and the transcription
      factor Adf-1 were obtained. While Ttk is thought to be a repressor of ftz
      stripes, we have shown that both Adf-1 and Ftz-F1 activate transcription in a
      binding site-dependent fashion. These two proteins are expressed ubiquitously at
      the time ftz is expressed in stripes, suggesting that either may activate striped
      expression alone or in combination with the Ftz protein. The roles of the nine
      nuclear factor binding sites were tested in vivo, by site-directed mutagenesis of
      individual and multiple sites. The three Ftz-F1-Adf-1-Ttk binding sites were
      found to be functionally redundant and essential for stripe expression in
      transgenic embryos. Thus, a biochemical analysis identified cis-acting regulatory
      modules that are required for gene expression in vivo. The finding of repeated
      binding sites for multiple nuclear proteins underscores the high degree of
      redundancy built into embryonic gene regulatory networks.

PMID- 9584180
TI  - Interaction of stat6 and NF-kappaB: direct association and synergistic activation
      of interleukin-4-induced transcription.
AB  - Signal transducer and activator of transcription 6 (Stat6) and NF-kappaB are
      widely distributed transcription factors which are induced by different stimuli
      and bind to distinct DNA sequence motifs. Interleukin-4 (IL-4), which activates
      Stat6, synergizes with activators of NF-kappaB to induce IL-4-responsive genes,
      but the molecular mechanism of this synergy is poorly understood. Using
      glutathione S-transferase pulldown assays and coimmunoprecipitation techniques,
      we find that NF-kappaB and tyrosine-phosphorylated Stat6 can directly bind each
      other in vitro and in vivo. An IL-4-inducible reporter gene containing both
      cognate binding sites in the promoter is synergistically activated in the
      presence of IL-4 when Stat6 and NF-kappaB proteins are coexpressed in human
      embryonic kidney 293 (HEK 293) cells. The same IL-4-inducible reporter gene is
      also synergistically activated by the endogenous Stat6 and NF-kappaB proteins in
      IL-4-stimulated I.29mu B lymphoma cells. Furthermore, Stat6 and NF-kappaB bind
      cooperatively to a DNA probe containing both sites, and the presence of a complex
      formed by their cooperative binding correlates with the synergistic activation of
      the promoter by Stat6 and NF-kappaB. We conclude that the direct interaction
      between Stat6 and NF-kappaB may provide a basis for synergistic activation of
      transcription by IL-4 and activators of NF-kappaB.

PMID- 9584181
TI  - GATA-4 and Nkx-2.5 coactivate Nkx-2 DNA binding targets: role for regulating
      early cardiac gene expression.
AB  - The cardiogenic homeodomain factor Nkx-2.5 and serum response factor (SRF)
      provide strong transcriptional coactivation of the cardiac alpha-actin (alphaCA)
      promoter in fibroblasts (C. Y. Chen and R. J. Schwartz, Mol. Cell. Biol. 16:6372
      6384, 1996). We demonstrate here that Nkx-2.5 also cooperates with GATA-4, a dual
      C-4 zinc finger transcription factor expressed in early cardiac progenitor cells,
      to activate the alphaCA promoter and a minimal promoter, containing only
      multimerized Nkx-2.5 DNA binding sites (NKEs), in heterologous CV-1 fibroblasts.
      Transcriptional activity requires the N-terminal activation domain of Nkx-2.5 and
      Nkx-2.5 binding activity through its homeodomain but does not require GATA-4's
      activation domain. The minimal interactive regions were mapped to the homeodomain
      of Nkx-2.5 and the second zinc finger of GATA-4. Removal of Nkx-2.5's C-terminal
      inhibitory domain stimulated robust transcriptional activity, comparable to the
      effects of GATA-4 on wild-type Nkx-2.5, which in part facilitated Nkx-2.5 DNA
      binding activity. We postulate the following simple model: GATA-4 induces a
      conformational change in Nkx-2.5 that displaces the C-terminal inhibitory domain,
      thus eliciting transcriptional activation of promoters containing Nkx-2.5 DNA
      binding targets. Therefore, alphaCa promoter activity appears to be regulated
      through the combinatorial interactions of at least three cardiac tissue-enriched
      transcription factors, Nkx-2.5, GATA-4, and SRF.

PMID- 9584182
TI  - Recruitment of octamer transcription factors to DNA by glucocorticoid receptor.
AB  - Glucocorticoid receptor (GR) and octamer transcription factors 1 and 2 (Oct-1/2)
      interact synergistically to activate the transcription of mouse mammary tumor
      virus and many cellular genes. Synergism correlates with cooperative DNA binding
      of the two factors in vitro. To examine the molecular basis for these cooperative
      interactions, we have studied the consequences of protein-protein binding between
      GR and Oct-1/2. We have determined that GR binds in solution to the octamer
      factor POU domain. Binding is mediated through an interface in the GR DNA binding
      domain that includes amino acids C500 and L501. In transfected mammalian cells, a
      transcriptionally inert wild-type but not an L501P GR peptide potentiated
      transcriptional activation by Oct-2 100-fold above the level that could be
      attained in the cell by expressing Oct-2 alone. Transcriptional activation
      correlated closely with a striking increase in the occupancy of octamer motifs
      adjacent to glucocorticoid response elements (GREs) on transiently transfected
      DNAs. Intriguingly, GR-Oct-1/2 binding was interrupted by the binding of GR to a
      GRE. We propose a model for transcriptional cooperativity in which GR-Oct-1/2
      binding promotes an increase in the local concentration of octamer factors over
      glucocorticoid-responsive regulatory regions. These results reveal
      transcriptional cooperativity through a direct protein interaction between two
      sequence-specific transcription factors that is mediated in a way that is
      expected to restrict transcriptional effects to regulatory regions with DNA
      binding sites for both factors.

PMID- 9584183
TI  - Functional mapping of the U3 small nucleolar RNA from the yeast Saccharomyces
      cerevisiae.
AB  - The U3 small nucleolar RNA participates in early events of eukaryotic pre-rRNA
      cleavage and is essential for formation of 18S rRNA. Using an in vivo system, we
      have developed a functional map of the U3 small nucleolar RNA from Saccharomyces
      cerevisiae. The test strain features a galactose-dependent U3 gene in the
      chromosome and a plasmid-encoded allele with a unique hybridization tag. Effects
      of mutations on U3 production were analyzed by evaluating RNA levels in cells
      grown on galactose medium, and effects on U3 function were assessed by growing
      cells on glucose medium. The major findings are as follows: (i) boxes C' and D
      and flanking helices are critical for U3 accumulation; (ii) boxes B and C are not
      essential for U3 production but are important for function, most likely due to
      binding of a trans-acting factor(s); (iii) the 5' portion of U3 is required for
      function but not stability; and, (iv) strikingly, the nonconserved hairpins 2, 3,
      and 4, which account for 50% of the molecule, are not required for accumulation
      or function.

PMID- 9584184
TI  - A critical role for cyclin C in promotion of the hematopoietic cell cycle by
      cooperation with c-Myc.
AB  - Cyclin C, a putative G1 cyclin, was originally isolated through its ability to
      complement a Saccharomyces cerevisiae strain lacking the G1 cyclin gene CLN1-3.
      Unlike cyclins D1 and E, the other two G1 cyclins obtained by the same approach
      and subsequently shown to play important roles during the G1/S transition, there
      is thus far no evidence to support the hypothesis that cyclin C is indeed
      critical for the promotion of cell cycle progression. In BAF-B03 cells, an
      interleukin 3 (IL-3)-dependent murine pro-B-cell line, cyclin C gene mRNA was
      induced at the G1/S phase upon IL-3 stimulation and reached a maximal level in
      the S phase. Enforced expression of exogenous cyclin C in this cell line failed
      to alter its growth properties. In the present study, we examined whether cyclin
      C is capable of cooperating with the cytokine-responsive immediate-early gene
      products c-Myc and c-Fos in the promotion of cell proliferation. We found that
      cyclin C is able to cooperate functionally with c-Myc, but not c-Fos, to induce
      both BAF-B03 cell proliferation in a cytokine-independent fashion and the
      formation of cell clusters. Furthermore, cyclin C was primarily responsible for
      the induction of cdc2 gene expression. Our data define a novel role for cyclin C
      in the regulation of both the G1/S and G2/M phases of the cell cycle, and this
      effect appears to be independent of the activity of CDK8 in the control of
      transcription.

PMID- 9584185
TI  - RNA-induced changes in the activity of the endonuclease encoded by the R2
      retrotransposable element.
AB  - R2 is a non-long terminal repeat retrotransposable element that inserts itself
      site specifically in the 28S rRNA genes of arthropods. The 120-kDa protein
      encoded by R2 has been shown to cleave one strand of the 28S gene at the target
      site and to use the 3' hydroxyl group generated from this nick to prime reverse
      transcription of its own RNA. This reaction has been termed target-primed reverse
      transcription (TPRT). Cleavage of the second DNA strand can occur in the presence
      or absence of reverse transcription but requires RNA. In this study, more
      sensitive in vitro assays have enabled further characterization of these
      reactions. R2 protein is capable of only a single round of TPRT because, once
      bound to the target DNA, it does not dissociate at physiological ionic strengths.
      Analysis of the role of RNA in the DNA cleavage reaction has revealed that the
      binding of RNA induces the R2 protein to form a multimeric complex. While larger
      complexes may form, the active component appears to be a dimer based on
      sedimentation studies and the change in stoichiometry of the cleavage reaction
      from a 1:1 ratio of protein subunit to target DNA in the absence of RNA to a 2:1
      ratio of subunit to DNA target in the presence of RNA. Nonspecific RNA can also
      induce formation of this RNA-protein (RNP) complex, but the association of the
      protein with R2 RNA is stronger as revealed by its stability in 0.4 M NaCl.
      Finally, formation of the RNP complex gives rise to a 150-fold increase in the
      ability of the R2 endonuclease to find the target site. The specificity of this
      RNP complex is sufficiently great that it can find the 28S gene target site and
      conduct the TPRT reaction with total genomic DNA.

PMID- 9584187
TI  - Concurrent replication and methylation at mammalian origins of replication.
AB  - Observations made with Escherichia coli have suggested that a lag between
      replication and methylation regulates initiation of replication. To address the
      question of whether a similar mechanism operates in mammalian cells, we have
      determined the temporal relationship between initiation of replication and
      methylation in mammalian cells both at a comprehensive level and at specific
      sites. First, newly synthesized DNA containing origins of replication was
      isolated from primate-transformed and primary cell lines (HeLa cells, primary
      human fibroblasts, African green monkey kidney fibroblasts [CV-1], and primary
      African green monkey kidney cells) by the nascent-strand extrusion method
      followed by sucrose gradient sedimentation. By a modified nearest-neighbor
      analysis, the levels of cytosine methylation residing in all four possible
      dinucleotide sequences of both nascent and genomic DNAs were determined. The
      levels of cytosine methylation observed in the nascent and genomic DNAs were
      equivalent, suggesting that DNA replication and methylation are concomitant
      events. Okazaki fragments were also demonstrated to be methylated, suggesting
      that the rapid kinetics of methylation is a feature of both the leading and the
      lagging strands of nascent DNA. However, in contrast to previous observations,
      neither nascent nor genomic DNA contained detectable levels of methylated
      cytosines at dinucleotide contexts other than CpG (i.e., CpA, CpC, and CpT are
      not methylated). The nearest-neighbor analysis also shows that cancer cell lines
      are hypermethylated in both nascent and genomic DNAs relative to the primary cell
      lines. The extent of methylation in nascent and genomic DNAs at specific sites
      was determined as well by bisulfite mapping of CpG sites at the lamin B2, c-myc,
      and beta-globin origins of replication. The methylation patterns of genomic and
      nascent clones are the same, confirming the hypothesis that methylation occurs
      concurrently with replication. Interestingly, the c-myc origin was found to be
      unmethylated in all clones tested. These results show that, like genes, different
      origins of replication exhibit different patterns of methylation. In summary, our
      results demonstrate tight coordination of DNA methylation and replication, which
      is consistent with recent observations showing that DNA methyltransferase is
      associated with proliferating cell nuclear antigen in the replication fork.

PMID- 9584186
TI  - Multiple mechanisms regulate imprinting of the mouse distal chromosome 7 gene
      cluster.
AB  - Genomic imprinting is an epigenetic process that results in the preferential
      silencing of one of the two parental copies of a gene. Although the precise
      mechanisms by which genomic imprinting occurs are unknown, the tendency of
      imprinted genes to exist in chromosomal clusters suggests long-range regulation
      through shared regulatory elements. We characterize a 800-kb region on the distal
      end of mouse chromosome 7 that contains a cluster of four maternally expressed
      genes, H19, Mash2, Kvlqt1, and p57(Kip2), as well as two paternally expressed
      genes, Igf2 and Ins2, and assess the expression and imprinting of Mash2, Kvlqt1,
      and p57(Kip2) during development in embryonic and extraembryonic tissues. Unlike
      Igf2 and Ins2, which depend on H19 for their imprinting, Mash2, p57(Kip2), and
      Kvlqt1 are unaffected by a deletion of the H19 gene region, suggesting that these
      more telomeric genes are not regulated by the mechanism that controls H19, Igf2,
      and Ins2. Mutations in human p57(Kip2) have been implicated in Beckwith-Wiedemann
      syndrome, a disease that has also been associated with loss of imprinting of
      IGF2. We find, however, that a deletion of the gene has no effect on imprinting
      within the cluster. Surprisingly, the three maternally expressed genes are
      regulated very differently by DNA methylation; p57(Kip2) is activated, Kvlqt1 is
      silenced, and Mash2 is unaffected in mice lacking DNA methyltransferase. We
      conclude that H19 is not a global regulator of imprinting on distal chromosome 7
      and that the telomeric genes are imprinted by a separate mechanism(s).

PMID- 9584188
TI  - Transactivation by retinoid X receptor-peroxisome proliferator-activated receptor
      gamma (PPARgamma) heterodimers: intermolecular synergy requires only the
      PPARgamma hormone-dependent activation function.
AB  - The ability of DNA sequence-specific transcription factors to synergistically
      activate transcription is a common property of genes transcribed by RNA
      polymerase II. The present work characterizes a unique form of intermolecular
      transcriptional synergy between two members of the nuclear hormone receptor
      superfamily. Heterodimers formed between peroxisome proliferator-activated
      receptor gamma (PPARgamma), an adipocyte-enriched member of the superfamily
      required for adipogenesis, and retinoid X receptors (RXRs) can activate
      transcription in response to ligands specific for either subunit of the dimer.
      Simultaneous treatment with ligands specific for both PPARgamma and RXR has a
      synergistic effect on the transactivation of reporter genes and on adipocyte
      differentiation in cultured cells. Mutation of the PPARgamma hormone-dependent
      activation domain (named tauc or AF-2) inhibits the ability of RXR-PPARgamma
      heterodimers to respond to ligands specific for either subunit. In contrast, the
      ability of RXR- and PPARgamma-specific ligands to synergize does not require the
      hormone-dependent activation domain of RXR. The results of in vitro and in vivo
      experiments indicate that binding of ligands to RXR alters the conformation of
      the dimerization partner, PPARgamma, and modulates the activity of the
      heterodimer in a manner independent of the RXR hormone-dependent activation
      domain.

PMID- 9584189
TI  - No requirement for V(D)J recombination in p53-deficient thymic lymphoma.
AB  - The p53 tumor suppressor is activated in response to a variety of cellular stress
      signals, although specific in vivo signals that trigger tumor suppression are
      unknown. In mouse thymocytes, where p53 inactivation leads to tumorigenesis,
      several observations suggest that V(D)J recombination of T-cell receptor (TCR)
      loci could provide a DNA damage signal triggering p53-dependent apoptosis and
      tumor suppression. Inactivation of p53 would allow V(D)J driven mutation of
      additional cancer genes, facilitating tumorigenesis. Here, we show that mice with
      a p53 deficiency in thymocytes and unable to carry out V(D)J recombination are
      not impaired in the development of thymoma. Recombination-activating gene (RAG)
      deficiencies were introduced into both p53-/- mice and TgTDeltaN transgenic mice,
      a strain in which 100% of the mice develop thymoma due to thymocyte-specific
      inactivation of p53 by a simian virus 40 T-antigen variant. V(D)J recombination
      was dispensable for tumorigenesis since thymomas developed with or without the
      RAG-1 or RAG-2 gene, although some delay was observed. When V(D)J recombination
      was suppressed by expression of rearranged TCR transgenes, 100% of the TgTDeltaN
      mice developed thymoma, surprisingly with reduced latency. Further introduction
      of a RAG deficiency into these mice had no impact on the timing or frequency of
      tumorigenesis. Finally, karyotype and chromosome painting analyses showed no
      evidence for TCR gene translocations in p53-deficient thymomas, although abundant
      aneuploidy involving frequent duplication of certain chromosomes was present.
      Thus, contrary to the current hypothesis, these studies indicate that signals
      other than V(D)J recombination promote p53 tumor suppression in thymocytes and
      that the mechanism of tumorigenesis is distinct from TCR translocation oncogene
      activation.

PMID- 9584190
TI  - Optimal activation of an endogenous gene by HOX11 requires the NH2-terminal 50
      amino acids.
AB  - The HOX11 homeobox gene was first identified through studies of the t(7;10) and
      t(10;14) chromosomal translocations of acute T-cell leukemia. In addition,
      analysis of Hox11-/- mice has demonstrated a critical role for this gene in
      murine spleen development. A possible mode of in vivo function for the HOX11
      protein in these two situations is regulation of target genes following DNA
      binding via the homeodomain, but little is known about how HOX11 regulates
      transcription in vivo. By performing transcriptional studies in yeast and
      mammalian one-hybrid systems, a modular transcriptional transactivation region at
      the NH2 terminus of HOX11 has been functionally dissected from other parts of the
      protein. This NH2-terminal region includes the previously identified short
      conserved Hep motif, which itself activates transcription in one-hybrid assays.
      The importance of the NH2-terminal region for the function of HOX11 in vivo was
      assayed by activating a HOX11-dependent gene in NIH 3T3 cells. Activation of this
      gene was found to be dependent upon an intact homeodomain in HOX11, but maximal
      activation was obtained only when the NH2-terminal 50 amino acids of HOX11 was
      present, showing that this region of HOX11 is important for in vivo
      transcriptional control of a chromosomal target gene.

PMID- 9584191
TI  - Involvement of microtubules in the regulation of Bcl2 phosphorylation and
      apoptosis through cyclic AMP-dependent protein kinase.
AB  - The Bcl2 family of proteins plays a significant role in regulation of apoptosis.
      In this study, the microtubule-damaging drugs paclitaxel, vincristine, and
      vinblastine induced Bcl2 hyperphosphorylation and apoptosis in MCF-7 and MDA-MB
      231 cells and reduced Bcl2-Bax dimerization. Paclitaxel or vincristine induced
      increased expression of Bax, while overexpression of Bcl2 in these cell lines
      counteracted the effects of low doses of these drugs. In addition, paclitaxel-
      and vincristine-induced activation of cyclic AMP (cAMP)-dependent protein kinase
      (protein kinase A [PKA]) induced Bcl2 hyperphosphorylation and apoptosis, which
      were blocked by the PKA inhibitor Rp diastereomers of cAMP (Rp-cAMP). This
      finding suggests that activation of PKA due to microtubule damage is an important
      event in Bcl2 hyperphosphorylation and induction of apoptosis. These microtubule
      damaging drugs caused growth arrest in G2-M phase of the cell cycle and had no
      effect on p53 induction, suggesting that hyperphosphorylation mediated
      inactivation of Bcl2 and apoptosis without the involvement of p53. By comparison,
      the DNA-damaging drugs methotrexate and doxorubicin had no effect on Bcl2
      hyperphosphorylation but induced p53 expression. Interestingly, paclitaxel or
      vincristine induced activation of caspase 3 and cleavage of poly(ADP-ribose)
      polymerase downstream of Bcl2 hyperphosphorylation. These data suggest that there
      may be a signaling cascade induced by agents that disrupt or damage the
      cytoskeleton that is distinct from (i.e., p53 independent), but perhaps related
      to (i.e., involves kinase activation and leads to apoptosis), the cellular
      response to DNA damage.

PMID- 9584192
TI  - Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on
      cardiomyocyte hypertrophy.
AB  - c-Jun N-terminal protein kinase (JNK) and p38, two distinct members of the
      mitogen-activated protein (MAP) kinase family, regulate gene expression in
      response to various extracellular stimuli, yet their physiological functions are
      not completely understood. In this report we show that JNK and p38 exerted
      opposing effects on the development of myocyte hypertrophy, which is an adaptive
      physiological process characterized by expression of embryonic genes and unique
      morphological changes. In rat neonatal ventricular myocytes, both JNK and p38
      were stimulated by hypertrophic agonists like endothelin-1, phenylephrine, and
      leukemia inhibitory factor. Expression of MAP kinase kinase 6b (EE), a
      constitutive activator of p38, stimulated the expression of atrial natriuretic
      factor (ANF), which is a genetic marker of in vivo cardiac hypertrophy.
      Activation of p38 was required for ANF expression induced by the hypertrophic
      agonists. Furthermore, a specific p38 inhibitor, SB202190, significantly changed
      hypertrophic morphology induced by the agonists. Surprisingly, activation of JNK
      led to inhibition of ANF expression induced by MEK kinase 1 (MEKK1) and the
      hypertrophic agonists. MEKK1-induced ANF expression was also negatively regulated
      by expression of c-Jun. Our results demonstrate that p38 mediates, but JNK
      suppresses, the development of myocyte hypertrophy.

PMID- 9584193
TI  - A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila
      immunity gene expression.
AB  - Accumulating evidence suggests that the insect and mammalian innate immune
      response is mediated by homologous regulatory components. Proinflammatory
      cytokines and bacterial lipopolysaccharide stimulate mammalian immunity by
      activating transcription factors such as NF-kappaB and AP-1. One of the responses
      evoked by these stimuli is the initiation of a kinase cascade that leads to the
      phosphorylation of p38 mitogen-activated protein (MAP) kinase on Thr and Tyr
      within the motif Thr-Gly-Tyr, which is located within subdomain VIII. We have
      investigated the possible involvement of the p38 MAP kinase pathway in the
      Drosophila immune response. Two genes that are highly homologous to the mammalian
      p38 MAP kinase were molecularly cloned and characterized. Furthermore, genes that
      encode two novel Drosophila MAP kinase kinases, D-MKK3 and D-MKK4, were
      identified. D-MKK3 is an efficient activator of both Drosophila p38 MAP kinases,
      while D-MKK4 is an activator of D-JNK but not D-p38. These data establish that
      Drosophila indeed possesses a conserved p38 MAP kinase signaling pathway. We have
      examined the role of the D-p38 MAP kinases in the regulation of insect immunity.
      The results revealed that one of the functions of D-p38 is to attenuate
      antimicrobial peptide gene expression following exposure to lipopolysaccharide.

PMID- 9584194
TI  - Cell cycle-regulated processing of HEF1 to multiple protein forms differentially
      targeted to multiple subcellular compartments.
AB  - HEF1, p130(Cas), and Efs/Sin constitute a family of multidomain docking proteins
      that have been implicated in coordinating the regulation of cell adhesion. Each
      of these proteins contains an SH3 domain, conferring association with focal
      adhesion kinase; a domain rich in SH2-binding sites, phosphorylated by or
      associating with a number of oncoproteins, including Abl, Crk, Fyn, and others;
      and a highly conserved carboxy-terminal domain. In this report, we show that the
      HEF1 protein is processed in a complex manner, with transfection of a single cDNA
      resulting in the generation of at least four protein species, p115(HEF1),
      p105(HEF1), p65(HEF1), and p55(HEF1). We show that p115(HEF1) and p105(HEF1) are
      different phosphorylation states of the full-length HEF1. p55(HEF1), however,
      encompasses only the amino-terminal end of the HEF1 coding sequence and arises
      via cleavage of full-length HEF1 at a caspase consensus site. We find that HEF1
      proteins are abundantly expressed in epithelial cells derived from breast and
      lung tissue in addition to the lymphoid cells in which they have been
      predominantly studied to date. In MCF-7 cells, we find that expression of the
      endogenous HEF1 proteins is cell cycle regulated, with p105(HEF1) and p115(HEF1)
      being rapidly upregulated upon induction of cell growth, whereas p55(HEF1) is
      produced specifically at mitosis. While p105(HEF1) and p115(HEF1) are
      predominantly cytoplasmic and localize to focal adhesions, p55(HEF1) unexpectedly
      is shown to associate with the mitotic spindle. In support of a role at the
      spindle, two-hybrid library screening with HEF1 identifies the human homolog of
      the G2/M spindle-regulatory protein Dim1p as a specific interactor with a region
      of HEF1 encompassed in p55(HEF1). In sum, these data suggest that HEF1 may
      directly connect morphological control-related signals with cell cycle regulation
      and thus play a role in pathways leading to the progression of cancer.

PMID- 9584195
TI  - The second-largest subunit of the mouse DNA polymerase alpha-primase complex
      facilitates both production and nuclear translocation of the catalytic subunit of
      DNA polymerase alpha.
AB  - DNA polymerase alpha-primase is a replication enzyme necessary for DNA
      replication in all eukaryotes examined so far. Mouse DNA polymerase alpha is made
      up of four subunits, the largest of which is the catalytic subunit with a
      molecular mass of 180 kDa (p180). This subunit exists as a tight complex with the
      second-largest subunit (p68), whose physiological role has remained unclear up
      until now. We set out to characterize these subunits individually or in
      combination by using a cDNA expression system in cultured mammalian cells.
      Coexpression of p68 markedly increased the protein level of p180, with the result
      that ectopically generated DNA polymerase activity was dramatically increased.
      Immunofluorescence analysis showed that while either singly expressed p180 or p68
      was localized in the cytoplasm, cotransfection of both subunits resulted in
      colocalization in the nucleus. We identified a putative nuclear localization
      signal for p180 (residues 1419 to 1437) and found that interaction with p68 is
      essential for p180 to translocate into the nucleus. These results indicate that
      association of p180 with p68 is important for both protein synthesis of p180 and
      translocation into the nucleus, implying that p68 plays a pivotal role in the
      newly synthesized DNA polymerase alpha complex.

PMID- 9584196
TI  - XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively
      regulates its activity following DNA damage.
AB  - Poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) is a zinc-finger DNA-binding
      protein that detects and signals DNA strand breaks generated directly or
      indirectly by genotoxic agents. In response to these breaks, the immediate
      poly(ADP-ribosyl)ation of nuclear proteins involved in chromatin architecture and
      DNA metabolism converts DNA damage into intracellular signals that can activate
      DNA repair programs or cell death options. To have greater insight into the
      physiological function of this enzyme, we have used the two-hybrid system to find
      genes encoding proteins putatively interacting with PARP. We have identified a
      physical association between PARP and the base excision repair (BER) protein
      XRCC1 (X-ray repair cross-complementing 1) in the Saccharomyces cerevisiae
      system, which was further confirmed to exist in mammalian cells. XRCC1 interacts
      with PARP by its central region (amino acids 301 to 402), which contains a BRCT
      (BRCA1 C terminus) module, a widespread motif in DNA repair and DNA damage
      responsive cell cycle checkpoint proteins. Overexpression of XRCC1 in Cos-7 or
      HeLa cells dramatically decreases PARP activity in vivo, reinforcing the
      potential protective function of PARP at DNA breaks. Given that XRCC1 is also
      associated with DNA ligase III via a second BRCT module and with DNA polymerase
      beta, our results provide strong evidence that PARP is a member of a BER
      multiprotein complex involved in the detection of DNA interruptions and possibly
      in the recruitment of XRCC1 and its partners for efficient processing of these
      breaks in a coordinated manner. The modular organizations of these interactors,
      associated with small conserved domains, may contribute to increasing the
      efficiency of the overall pathway.

PMID- 9584197
TI  - Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed:
      indication for separate Pc-G complexes.
AB  - The Polycomb group (Pc-G) constitutes an important, functionally conserved group
      of proteins, required to stably maintain inactive homeobox genes repressed during
      development. Drosophila extra sex combs (esc) and its mammalian homolog embryonic
      ectoderm development (eed) are special Pc-G members, in that they are required
      early during development when Pc-G repression is initiated, a process that is
      still poorly understood. To get insight in the molecular function of Eed, we
      searched for Eed-interacting proteins, using the yeast two-hybrid method. Here we
      describe the specific in vivo binding of Eed to Enx1 and Enx2, two mammalian
      homologs of the essential Drosophila Pc-G gene Enhancer-of-zeste [E(z)]. No
      direct biochemical interactions were found between Eed/Enx and a previously
      characterized mouse Pc-G protein complex, containing several mouse Pc-G proteins
      including mouse polyhomeotic (Mph1). This suggests that different Pc-G complexes
      with distinct functions may exist. However, partial colocalization of Enx1 and
      Mph1 to subnuclear domains may point to more transient interactions between these
      complexes, in support of a bridging role for Enx1.

PMID- 9584198
TI  - The nucleic acid binding activity of bleomycin hydrolase is involved in bleomycin
      detoxification.
AB  - Yeast bleomycin hydrolase, Gal6p, is a cysteine peptidase that detoxifies the
      anticancer drug bleomycin. Gal6p is a dual-function protein capable of both
      nucleic acid binding and peptide cleavage. We now demonstrate that Gal6p exhibits
      sequence-independent, high-affinity binding to single-stranded DNA, nicked double
      stranded DNA, and RNA. A region of the protein that is involved in binding both
      RNA and DNA substrates is delineated. Immunolocalization reveals that the Gal6
      protein is chiefly cytoplasmic and thus may be involved in binding cellular RNAs.
      Variant Gal6 proteins that fail to bind nucleic acid also exhibit reduced ability
      to protect cells from bleomycin toxicity, suggesting that the nucleic acid
      binding activity of Gal6p is important in bleomycin detoxification and may be
      involved in its normal biological functions.

PMID- 9584199
TI  - Characterization of interactions between the mammalian polycomb-group proteins
      Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group
      protein complexes.
AB  - In Drosophila melanogaster, the Polycomb-group (PcG) and trithorax-group (trxG)
      genes have been identified as repressors and activators, respectively, of gene
      expression. Both groups of genes are required for the stable transmission of gene
      expression patterns to progeny cells throughout development. Several lines of
      evidence suggest a functional interaction between the PcG and trxG proteins. For
      example, genetic evidence indicates that the enhancer of zeste [E(z)] gene can be
      considered both a PcG and a trxG gene. To better understand the molecular
      interactions in which the E(z) protein is involved, we performed a two-hybrid
      screen with Enx1/EZH2, a mammalian homolog of E(z), as the target. We report the
      identification of the human EED protein, which interacts with Enx1/EZH2. EED is
      the human homolog of eed, a murine PcG gene which has extensive homology with the
      Drosophila PcG gene extra sex combs (esc). Enx1/EZH2 and EED coimmunoprecipitate,
      indicating that they also interact in vivo. However, Enx1/EZH2 and EED do not
      coimmunoprecipitate with other human PcG proteins, such as HPC2 and BMI1.
      Furthermore, unlike HPC2 and BMI1, which colocalize in nuclear domains of U-2 OS
      osteosarcoma cells, Enx1/EZH2 and EED do not colocalize with HPC2 or BMI1. Our
      findings indicate that Enx1/EZH2 and EED are members of a class of PcG proteins
      that is distinct from previously described human PcG proteins.

PMID- 9584200
TI  - p300/CREB binding protein-related protein p270 is a component of mammalian
      SWI/SNF complexes.
AB  - p300 and the closely related CREB binding protein (CBP) are transcriptional
      adaptors that are present in intracellular complexes with TATA binding protein
      (TBP) and bind to upstream activators including p53 and nuclear hormone
      receptors. They have intrinsic and associated histone acetyltransferase activity,
      suggesting that chromatin modification is an essential part of their role in
      regulating transcription. Detailed characterization of a panel of antibodies
      raised against p300/CBP has revealed the existence of a 270-kDa cellular protein,
      p270, distinct from p300 and CBP but sharing at least two independent epitopes
      with p300. The subset of p300/CBP-derived antibodies that cross-reacts with p270
      consistently coprecipitates a series a cellular proteins with relative molecular
      masses ranging from 44 to 190 kDa. Purification and analysis of various proteins
      in this group reveals that they are components of the human SWI/SNF complex and
      that p270 is an integral member of this complex.

PMID- 9584201
TI  - The MYND motif is required for repression of basal transcription from the
      multidrug resistance 1 promoter by the t(8;21) fusion protein.
AB  - Chromosomal translocations in acute leukemia that affect the AML-1/CBFbeta
      transcription factor complex create dominant inhibitory proteins. However, the
      mechanisms by which these proteins act remain obscure. Here we demonstrate that
      the multidrug resistance 1 (MDR-1) promoter is a target for AML/ETO
      transcriptional repression. This repression is of basal, not activated,
      expression from the MDR-1 promoter and thus represents a new mechanism for
      AML/ETO function. We have defined two domains in AML/ETO that are required for
      repression of basal transcription from the MDR-1 promoter: a hydrophobic heptad
      repeat (HHR) motif and a conserved zinc finger (ZnF) domain termed the MYND
      domain. The HHR mediates formation of AML/ETO homodimers and AML/ETO-ETO
      heterodimers. Single serine substitutions at conserved cysteine residues within
      the predicted ZnFs also abrogate transcriptional repression. Finally, we observe
      that AML/ETO can also inhibit Ets-1 activation of the MDR-1 promoter, indicating
      that AML/ETO can disrupt both basal and Ets-1-dependent transcription. The
      fortuitous inhibition of MDR-1 expression in t(8;21)-containing leukemias may
      contribute to the favorable response of these patients to chemotherapeutic drugs.

PMID- 9584202
TI  - L-DNase II, a molecule that links proteases and endonucleases in apoptosis,
      derives from the ubiquitous serpin leukocyte elastase inhibitor.
AB  - The most widely recognized biochemical change associated with the majority of
      apoptotic systems is the degradation of genomic DNA. Among the enzymes that may
      participate in this cleavage, the acidic cation-independent DNase II is a likely
      candidate since it is activated in many apoptotic cells. To better understand its
      role, we purified and sequenced a DNase II extracted from porcine spleen. Protein
      sequencing of random peptides demonstrated that this enzyme is derived from a
      ubiquitous serpin, the leukocyte elastase inhibitor (LEI), by an acidic-dependent
      posttranslational modification or by digestion with elastase. We call this novel
      enzyme L-DNase II. In vitro experiments with purified recombinant LEI show that
      the native form has no effect on purified nuclei whereas its posttranslationally
      activated form induces pycnosis and DNA degradation. Antibodies directed against
      L-DNase II showed, in different cell lines, an increased expression and a nuclear
      translocation of this enzyme during apoptosis. Since the appearance of the
      endonuclease activity results in a loss of the anti-protease properties of LEI,
      the transformation from LEI to L-DNase II may act as a switch of protease and
      nuclease pathways, each of which is activated during apoptosis.

PMID- 9584203
TI  - Human T-cell leukemia virus type 1 Tax and cell cycle progression: role of cyclin
      D-cdk and p110Rb.
AB  - Human T-cell leukemia virus type 1 is etiologically linked to the development of
      adult T-cell leukemia and various human neuropathies. The Tax protein of human T
      cell leukemia virus type I has been implicated in cellular transformation. Like
      other oncoproteins, such as Myc, Jun, and Fos, Tax is a transcriptional
      activator. How it mechanistically dysregulates the cell cycle is unclear.
      Previously, it was suggested that Tax affects cell-phase transition by forming a
      direct protein-protein complex with p16(INK4a), thereby inactivating an inhibitor
      of G1-to-S-phase progression. Here we show that, in T cells deleted for
      p16(INK4a), Tax can compel an egress of cells from G0/G1 into S despite the
      absence of serum. We also show that in undifferentiated myocytes, expression of
      Tax represses cellular differentiation. In both settings, Tax expression was
      found to increase cyclin D-cdk activity and to enhance pRb phosphorylation. In T
      cells, a Tax-associated increase in steady-state E2F2 protein was also
      documented. In searching for a molecular explanation for these observations, we
      found that Tax forms a protein-protein complex with cyclin D3, whereas a point
      mutated and transcriptionally inert Tax mutant failed to form such a complex.
      Interestingly, expression of wild-type Tax protein in cells was also correlated
      with the induction of a novel hyperphosphorylated cyclin D3 protein. Taken
      together, these findings suggest that Tax might directly influence cyclin D-cdk
      activity and function, perhaps by a route independent of cdk inhibitors such as
      p16(INK4a).

PMID- 9584205
TI  - Interaction of beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluoro-CTP with human
      immunodeficiency virus-1 reverse transcriptase and human DNA polymerases:
      implications for human immunodeficiency virus drug design.
AB  - The work reported in this article has evaluated the relative molecular activity
      of the 5'-triphosphate of a novel beta-L-nucleoside with an unsaturated ribose
      residue, beta-L-2', 3'-dideoxy-2',3'-didehydro-5-fluorocytidine (beta-L-Fd4CTP),
      with that of beta-L-2',3'-dideoxy-5-fluorocytidine (beta-L-FddCTP) and 2', 3'
      dideoxycytidine (ddCTP), on DNA strand elongation by human immunodeficiency virus
      1 reverse transcriptase (HIV RT) and human DNA polymerases alpha (pol alpha),
      beta (pol beta), gamma (pol gamma), and epsilon (pol epsilon). The concentrations
      of beta-L-Fd4CTP that inhibited the yield of products by 50% were 0.20 micro M,
      1.8 micro M, and 4.0 micro M for HIV RT, pol gamma, and pol beta, respectively.
      The beta-L-Fd4CTP at a concentration as high as 40 micro M had no inhibitory
      effect on pol epsilon, but could inhibit pol alpha by 10-20% at 20 micro M. The
      Km and relative Vmax values of beta-L-Fd4CTP, beta-L-FddCTP, and ddCTP for
      incorporation into the standing start point of 5'-[32P]-oligonucleotide primer
      annealed with M13mp19 phage DNA by HIV RT and human DNA polymerases were
      evaluated. The efficiency of incorporation (Vmax/Km) of beta-L-Fd4CTP by HIV RT
      was about 4-fold and 12-fold higher than that of ddCTP and beta-L-FddCTP,
      respectively. In contrast, the Vmax/Km ratio of beta-L-Fd4CTP for pol gamma was 7
      fold lower than that of ddCTP, but 4-fold higher than that of beta-L-FddCTP. Pol
      alpha could use beta-L-Fd4CTP as a substrate, but only at a high concentration
      (>20 micro M). Incorporation of beta-L-Fd4CTP by pol epsilon could not be
      detected. A hypothesis about the preferable recognition of the 2',3'-dideoxy
      2',3'-didehydro- structure of beta-L-Fd4CTP to that of the 2',3'-dideoxy
      structure of beta-L-FddCTP by HIV RT is discussed.

PMID- 9584206
TI  - Differential uncoupling of A1 adenosine and D2 dopamine receptors by suramin and
      didemethylated suramin (NF037).
AB  - Suramin analogues uncouple two Gi/Go-coupled receptors, the D2 dopamine receptor
      in rat striatum and the A1 adenosine receptor in human cerebral cortex, with
      distinct structure-activity relations. This discrepancy may reflect true
      differences in the affinity of the analogues for specific receptor/G protein
      complexes or may be attributable to differences in species or in the tissue
      source used. We addressed this question by using human embryonic kidney 293 cells
      that stably express the human A1 and rat A1 receptor and the human D2 receptor.
      Suramin is 10-fold more potent than its didemethylated analogue NF037 in
      inhibiting the interaction between G proteins and the rat A1 or human A1
      receptor; in contrast, both compounds are equipotent in uncoupling the D2
      receptor. These differences are observed regardless of whether (1) inhibition of
      high affinity agonist binding to the receptors or (2) agonist-stimulated
      GTPgammaS binding is used as readout, (3) the receptors are allowed to interact
      with the G protein complement in human embryonic kidney 293 cell membranes, or
      (4) the receptors are forced to interact with a defined G protein alpha subunit
      (i.e., after reconstituting pertussis toxin-treated membranes with exogenous rGi
      alpha-1). The apparent affinity of suramin depends in a linear manner on receptor
      occupancy, which shows that suramin and the receptor compete for the G protein.
      Finally, the affinity of the receptors for rGi alpha-1 (human A1 > rat A1 > human
      D2) is inversely correlated with the potency of suramin in uncoupling ternary
      complexes formed by these receptors and thus determines the selectivity of the
      suramin analogues for specific receptor/G protein tandems.

PMID- 9584207
TI  - Cisplatin- and paclitaxel-induced apoptosis of ovarian carcinoma cells and the
      relationship between bax and bak up-regulation and the functional status of p53.
AB  - We investigated the roles of p53 and Bcl-2 homologues in the induction of
      apoptosis by cisplatin and paclitaxel in wild-type p53-expressing human ovarian
      carcinoma cells and cisplatin-resistant derivatives that have lost p53 function.
      Cisplatin induced apoptosis in parental A2780 but not in cisplatin-resistant
      A2780/cp70 cells, whereas paclitaxel induced apoptosis in both cell lines.
      Immunoprecipitation of p53 using antibodies specific for p53 conformation (pAb
      1620 and pAb 240) showed that there were no relative changes in p53 conformation
      before and after cisplatin treatment in either cell line. A2780/cp70 cells have
      lost p53 function, yet they have wild-type p53 gene sequence. However, A2780/cp70
      cells constitutively express more p53 in a form detected by pAb 240, an antibody
      that also detects mutant conformations of p53 that are transcriptionally
      inactive. There were no changes in levels of Bcl-2, Bcl-XL, or 24-kDa Bax over 72
      hr after exposure to cisplatin or paclitaxel, but each agent led to up-regulation
      of Bak and 21-kDa Bax in A2780 cells. Paclitaxel, but not cisplatin, increased
      Bak and 21-kDa Bax levels in A2780/cp70 cells. These data suggest that apoptosis
      in A2780 and A2780/cp70 is associated with an increased level of Bak and 21 kDa
      Bax after drug-induced damage and that functional p53 may be required for this
      effect after cisplatin but not after paclitaxel.

PMID- 9584204
TI  - The position and length of the steroid-dependent hypersensitive region in the
      mouse mammary tumor virus long terminal repeat are invariant despite multiple
      nucleosome B frames.
AB  - Stimulation of the mouse mammary tumor virus with steroids results in the
      generation of a DNase I-hypersensitive region (HSR) spanning the hormone
      responsive element (HRE) in the long terminal repeat. Restriction enzymes were
      used to characterize the accessibility of various sites within the HSR of mouse
      mammary tumor virus long terminal repeat-reporter constructions in four different
      cell lines. The glucocorticoid-dependent HSR was found to span minimally 187
      bases, a stretch of DNA longer than that associated with histones in the core
      particle. Although the 5'-most receptor binding site within the HRE is downstream
      of -190, hypersensitive sites were found further upstream to at least -295. The
      relationship in the accessibility between pairs of sites in the vicinity of the
      HSR was further examined in one cell line by a two-enzyme restriction access
      assay. In the uninduced state, the accessibilities at these sites were found to
      be independent of each other. In contrast, when stimulated with hormone, the
      accessibilities at these sites were observed to become linked. That is, once a
      distinct promoter was activated, all of the sites within the HSR of that molecule
      became accessible. The HSR formed along an invariant stretch of DNA sequence
      despite the multiplicity of nucleosome frames in the nucleosome B region, where
      the HRE is located. The results indicate that the macroscopic length of the HSR
      does not arise from core length-remodeling events in molecules containing Nuc-B
      in alternative positions.

PMID- 9584208
TI  - A role for a wortmannin-sensitive phosphatidylinositol-4-kinase in the
      endocytosis of muscarinic cholinergic receptors.
AB  - A role for phosphoinositides in the endocytosis of muscarinic cholinergic
      receptors (mAChRs) has been investigated via inhibition of the activity of
      phosphatidylinositol-4-kinase (PI4K). Pretreatment of SH-SY5Y neuroblastoma cells
      with micromolar concentrations of wortmannin (WT), LY-294002, or phenylarsine
      oxide (PAO), three chemically distinct agents known to inhibit PI4K, resulted in
      both an inhibition of agonist-induced endocytosis of mAChRs and a selective
      reduction in the 32P-labeling of phosphatidylinositol-4-phosphate. PAO-mediated
      inhibition of both receptor endocytosis and phosphoinositide synthesis could be
      fully reversed by inclusion of the bifunctional thiol 2, 3-dimercaptopropanol.
      The requirement for phosphoinositide synthesis in mAChR endocytosis was
      independent of a role for these lipids in the maintenance of the cytoskeleton
      because disruption of the latter with cytochalasin D, ML-7, or colchicine failed
      to inhibit receptor internalization. Determination of PI4K activity in
      subcellular fractions of SH-SY5Y cells indicated that enzyme activity in
      fractions enriched in endocytic vesicles and cytosol was preferentially inhibited
      by WT, LY-294002, and PAO, a profile consistent with the subcellular distribution
      of the 110-kDa beta isoform of PI4K, as determined by Western blot analysis.
      Activity of PI4Kbeta present in immunoprecipitated cell lysates was inhibited
      >75% by inclusion of each of the three inhibitors. These results indicate that
      ongoing synthesis of phosphoinositides is necessary for mAChR endocytosis and
      that the activity of a WT-sensitive form of PI4K, such as PI4Kbeta, is required.

PMID- 9584209
TI  - Thrombin and phorbol esters potentiate Gs-mediated cAMP formation in intact human
      erythroid progenitors via two synergistic signaling pathways converging on
      adenylyl cyclase type VII.
AB  - In intact, but not in permeabilized, human erythroid progenitor cells, thrombin
      and phorbol esters potentiate cellular cAMP formation in response to Gs-coupled
      receptor agonists such as prostaglandin E1 (PGE1). We show here that the two
      agonists achieve their phenotypically similar effects by using distinctly
      different signaling pathways, both of which require protein kinase C (PKC)
      activation. After short term exposure (11 min), phorbol esters caused an alkaline
      shift of cellular pH by approximately 0.1 unit, resulting in a 1.5-2-fold
      increase in PGE1-induced cAMP formation. The effect of phorbol esters was
      inhibited by 5-(N-ethyl-N-isopropyl)amiloride, a specific inhibitor of the Na+/H+
      exchanger, and by the PKC inhibitors GF 109203X, Go 6976, and staurosporine.
      Thrombin increased cellular pH by only 0.02-0.05 unit but seemed to potentiate
      PGE1-stimulated cAMP formation by an effect on the Gs-activated adenylyl cyclase
      involving a Ca2+-independent (novel) PKC. This effect was inhibited by GF 109203X
      and staurosporine but was resistant to 5-(N-ethyl-N-isopropyl)amiloride or Go
      6976. Inactivation of PKC by incubation of the cells in the presence of 10 nM
      phorbol-12-myristate-13-acetate for 18 hr completely abolished the potentiating
      effect of thrombin on cyclase activity, whereas the pH-dependent stimulation was
      fully retained. Northern blots with specific cDNA probes and a lack of Ca2+
      sensitivity indicate that progenitor cells predominantly express adenylyl cyclase
      type VII. Our results suggest that in normal human erythroid progenitors,
      thrombin can activate pH-dependent and -independent, PKC-linked pathways
      converging on adenylyl cyclase type VII to potentiate cAMP formation in response
      to Gs-coupled receptor agonists.

PMID- 9584210
TI  - DNA interactions of a novel platinum drug, cis-[PtCl(NH3)2(N7-acyclovir)]+.
AB  - We synthesized a novel platinum drug, cis-[PtCl(NH3)2(N7-ACV)]+, in which ACV is
      the antiviral drug acyclovir [a deoxyriboguanosine analogue, 9-(2
      hydroxyethoxymethyl)guanine]. This new compound exhibits antiviral efficacy in
      vitro and exhibits an antitumor activity profile different from that of cisplatin
      [Metal-Based Drugs 2:249-256 (1995)]. To contribute to understanding the
      mechanisms underlying biological activity of this new compound, we studied
      modifications of natural and synthetic DNAs in cell-free media by cis
      [PtCl(NH3)2(N7-ACV)]+ by various biochemical and biophysical methods. The results
      indicated that the major DNA adduct of cis-[PtCl(NH3)2(N7-ACV)]+ was a stable
      monofunctional adduct at guanine residues. In contrast to DNA adducts of other
      monodentate and clinically ineffective platinum(II) compounds, the adducts of cis
      [PtCl(NH3)2(N7-ACV)]+ terminated in vitro DNA and RNA synthesis. In addition,
      although DNA adducts of cis-[PtCl(NH3)2(N7-ACV)]+ and cisplatin were different,
      some properties of DNA modified by either compound were qualitatively similar.
      Such similarities were not noticed if DNA modifications by other ineffective
      monofunctional platinum(II) complexes were investigated. Thus, the DNA binding
      mode of monofunctional cis-[PtCl(NH3)2(N7-ACV)]+ was different from that of other
      monofunctional but ineffective platinum(II) complexes. It has been suggested that
      the unique capability of cis-[PtCl(NH3)2(N7-ACV)]+ to modify DNA may be relevant
      to a distinct antitumor efficiency of this novel drug in comparison with
      cisplatin. It also has been suggested that at least some aspects of DNA
      interactions of cis-[PtCl(NH3)2(ACV)]+ revealed in the current study could be
      exploited in the search for and development of new antiviral platinum complexes
      containing, as a part of the coordination sphere, antiviral nucleosides.

PMID- 9584211
TI  - Agonist interactions with chimeric and mutant beta1- and beta3-adrenergic
      receptors: involvement of the seventh transmembrane region in conferring subtype
      specificity.
AB  - beta1- and beta3-adrenergic receptors (AR) are the predominant beta-AR subtypes
      in adipocytes, and analysis of native and recombinant beta-AR has revealed
      several pharmacological and biochemical differences between these subtypes. This
      study used chimeric and mutated rat beta-AR expressed in Chinese hamster ovary
      cells to examine the basis of certain characteristic differences in the agonist
      properties of catecholamines and prototypic beta3-AR agonists. The exchange of
      sequence beyond transmembrane (TM) region 6 between the beta-AR subtypes had
      dramatic and reciprocal effects on the affinity and efficacy of the prototypic
      beta3-AR agonists BRL 37,344 and CL 316,243, without affecting the interactions
      with catecholamines. Mutation of Phe350 and Phe351 in TM7 of the beta1-AR to Ala
      and Leu found in the beta3-AR was sufficient to allow activation by prototypic
      beta3-AR agonists. Interestingly, this mutation did not affect catecholamine
      action and it did not impair the ability of propranolol to block the actions of
      isoproterenol or the selective beta3-AR agonists. beta1-AR containing beta3-AR
      sequence from predicted TM5 through TM6 exhibited reduced affinity for
      catecholamines without altering agonist potency, suggesting enhanced coupling
      efficiency. Inclusion of the homologous beta1-AR sequence in the beta3-AR,
      however, did not produce reciprocal effects. These results are the first to
      define a major determinant of beta3-AR subtype-selective agonism in TM7 and
      demonstrate that the determinants of selective phenethanolamines, catecholamines,
      and propranolol action are distinct.

PMID- 9584212
TI  - Guanine nucleotide-sensitive inhibition of L-type Ca2+ current by
      lysosphingolipids in RINm5F insulinoma cells.
AB  - The lysosphingolipids sphingosine-1-phosphate (SPP) and
      sphingosylphosphorylcholine (SPPC) reportedly increase free cytosolic Ca2+
      concentration ([Ca2+]i) in a variety of cell types, apparently by activating G
      protein-coupled plasma membrane receptors. We investigated whether and how
      sphingolipids modulate Ca2+ homeostasis in the insulinoma cell line RINm5F. The
      addition of SPPC and glucopsychosine (GPS) did not affect basal [Ca2+]i but
      inhibited the KCl (30 mM)-induced increase in [Ca2+]i in a pertussis toxin
      insensitive and concentration-dependent manner (EC50 approximately 5 micro M).
      Similar inhibitory effects were observed with dihydro-SPPC and psychosine,
      whereas SPP and various N-acylated sphingolipids (at 10 micro M each) had little
      or no effect on the KCl-induced [Ca2+]i increase. Because in RINm5F cells the
      primary pathway for depolarization-induced [Ca2+]i increase are L-type Ca2+
      channels, we studied whether sphingolipids reduce L-type Ca2+ current (ICa.L).
      When added to the bath, GPS and SPPC, but not SPP (10 micro M each), rapidly
      reduced maximal ICa.L by approximately 35%, similar to the alpha2-adrenoceptor
      agonist clonidine (30 micro M). However, when applied internally, GPS had no
      effect on ICa. L. When the electrode solution contained the stable GDP analog
      guanosine-5'-O-(2-thio)diphosphate (1 and 10 mM), the inhibitory effect of GPS
      was abolished. In conclusion, a novel cellular action of lysosphingolipids is
      observed in RINm5F cells (i.e., a guanine nucleotide-sensitive inhibition of L
      type Ca2+ currents). The pharmacological profile of this inhibition is unique and
      unlike any known lysosphingolipid receptor-mediated action.

PMID- 9584213
TI  - Location of a high affinity Zn2+ binding site in the channel of alpha1beta1 gamma
      aminobutyric acidA receptors.
AB  - Zn2+ inhibits currents through gamma-aminobutyric acid (GABA)A receptors. Its
      affinity depends on the subunit composition; alpha1beta1 receptors are inhibited
      with high affinity (IC50 = 0.54 micro M). We sought to identify the residues that
      form this high affinity Zn2+ binding site. beta1His267 aligns with alpha1Ser272,
      a residue near the extracellular end of the M2 membrane-spanning segment that we
      previously demonstrated to be exposed in the channel. The Zn2+ affinity of
      alpha1beta1 H267S was reduced by 300-fold (IC50 = 161 micro M). Addition of a
      histidine at the aligned position in alpha1 creates a receptor, alpha1S272Hbeta1,
      that should have five channel-lining histidines; the Zn2+ affinity was increased
      20-fold (IC50 = 0.025 micro M). Shifting the position of the histidine from the
      beta1 subunit to the aligned position in alpha1 with the two mutants
      alpha1S272Hbeta1H267S reduced the affinity (IC50 = 26 micro M) compared with wild
      type. We infer that the high affinity Zn2+ binding site involves beta1His267 from
      at least two subunits. For two histidines to interact with a Zn2+ ion, the alpha
      carbons must be separated by <13 A. This limits the separation of the subunits
      and provides a constraint on the possible quaternary structures of the channel.
      The ability of a divalent cation to penetrate from the extracellular end of the
      channel to beta1His267 implies that the charge-selectivity filter, the structure
      that discriminates between anions and cations, is located at a more cytoplasmic
      position than beta1His267; this is consistent with our previous work that showed
      that positively charged sulfhydryl-specific reagents reacted with an engineered
      cysteine residue as cytoplasmic as alpha1T261C.

PMID- 9584214
TI  - Binding sites and transduction process of the cholecystokininB receptor:
      involvement of highly conserved aromatic residues of the transmembrane domains
      evidenced by site-directed mutagenesis.
AB  - The functional significance of the extracellular amino-terminal region and of
      three highly conserved aromatic residues present in the fifth (TM-V) and sixth
      (TM-VI) transmembrane domains of the rat cholecystokinin (CCK)B receptor,
      transfected in Cos-7 cells, was investigated by site-directed mutagenesis. The
      amino-terminal region of the CCKB receptor seemed to be weakly involved in CCK
      binding in that the affinities of CCK8 and selective agonists and antagonists
      were not modified by truncation of this region. Substitution of Phe347 in TM-VI
      with alanine produced a mutant receptor that displays the same affinity and
      selectivity as the wild-type receptor for agonists, but a slightly increased
      affinity for the selective CCKB antagonist L-365,260. However, the addition of
      saturating CCK8 concentrations to cells expressing this mutant did not result in
      the production of inositol phosphates, demonstrating the critical role of Phe347
      in CCKB receptor to G protein coupling. Substitution of Phe227 with alanine was
      without effect on the affinities of CCKB ligands and on phosphoinositide turnover
      but modified the affinity of the CCKA antagonist L-364,718. Residue Trp351
      located within the CCKB receptor TM-VI is involved in the binding of CCK8 and
      CCK4 and of the CCK4-based antagonist PD-134,308, as illustrated by the decreased
      affinities of these ligands in W351A mutant. The lower affinity for CCK8 observed
      with this mutated CCKB receptor accounts for the higher EC50 value for
      phosphotidylinositol hydrolysis. This study suggests that at least part of the
      binding site for the agonist is located inside the transmembrane domain of the
      CCKB receptor, partially overlapping that of antagonists, and gives new insights
      into the regions involved in the transduction process.

PMID- 9584215
TI  - Inverse agonists and neutral antagonists of recombinant human A1 adenosine
      receptors stably expressed in Chinese hamster ovary cells.
AB  - Receptor antagonists can be classified as neutral antagonists or antagonists with
      inverse agonist activity based on their effectiveness to reduce the spontaneous
      agonist-independent activity of receptors. The goals of this study were to (1)
      demonstrate that A1-adenosine receptors (A1AdoRs) expressed at high density (4000
      8000 fmol/mg of protein) in Chinese hamster ovary (CHO) cells cause constitutive
      activation of inhibitory G proteins and inhibition of adenylyl cyclase activity
      and (2) identify both neutral A1AdoR antagonists and antagonists with inverse
      agonist activity. The activity of A1AdoR agonists and antagonists was determined
      by assays of both specific binding of [35S]guanosine-5'-O-(3-thio)triphosphate
      ([35S]GTPgammaS) to membranes and cAMP content of intact cells in the presence of
      adenosine deaminase (2-5 units/ml). The A1AdoR agonist N6-cyclopentyladenosine
      (CPA) significantly increased binding of [35S]GTPgammaS by 241 +/- 7% compared
      with control. The A1AdoR antagonists N-0861, N-0840, and WRC-0342 did not alter
      binding of [35S]GTPgammaS, whereas the antagonists 8-cyclopentyl-1, 3
      dipropylxanthine (CPX), CGS-15943, xanthine amine congener, and WRC-0571
      significantly reduced binding of [35S]GTPgammaS by 28-53% from control,
      respectively. The effects of both the agonist N6-cyclopentyladenosine (CPA) and
      the antagonist CPX to alter binding of [35S]GTPgammaS were attenuated by 1 micro
      M N-0861. CPA reduced cAMP content of forskolin-stimulated CHO:A1AdoR cells, and
      N-0861 and WRC-0342 did not alter cAMP content, but the antagonists CPX and WRC
      0571 increased the cAMP content of CHO:A1AdoR cells. The effects of both CPX and
      WRC-0571 to increase cAMP content of forskolin-stimulated CHO:A1AdoR cells were
      attenuated by either N-0861 or WRC-0342. The results indicate that both N-0861
      and WRC-0342 are neutral antagonists, whereas both CPX and WRC-0571 are
      antagonists with inverse agonist activity.

PMID- 9584216
TI  - An anionic residue at position 564 is important for maintaining the inactive
      conformation of the human lutropin/choriogonadotropin receptor.
AB  - Gonadotropin-independent, male-limited precocious puberty is caused by a variety
      of mutations in the lutropin/choriogonadotropin receptor (LHR) that produce
      constitutive receptor activation. Two of these mutations encode replacement of
      conserved aspartate residues at positions 564 and 578 with glycine. We previously
      used site-directed mutagenesis to study the functional role of the Asp578 side
      chain in transmembrane helix 6, and concluded that it is its ability to serve as
      a properly positioned interhelical hydrogen bond acceptor, rather than its
      negative charge, that is important for stabilizing the inactive state of the LHR.
      We now report the effects of substituting seven different amino acids for the
      Asp564 residue located at the carboxyl terminus of the third intracellular loop.
      Glycine, alanine, valine, leucine, phenylalanine, and asparagine produced
      constitutive activation in a COS-7 cell expression system (3-5-fold increase in
      basal cAMP), but glutamate did not, indicating that a negative charge at position
      564 may be important for maintaining the inactive LHR conformation.
      Characterization of double-mutant receptors showed that certain substitutions at
      Asp564 and Asp578 have a cumulative effect on basal receptor activity, perhaps
      because they mimic different aspects of the activation process normally triggered
      by hormone binding.

PMID- 9584217
TI  - Isoform-specific inhibition of L-type calcium channels by dihydropyridines is
      independent of isoform-specific gating properties.
AB  - Dihydropyridines (DHPs) block L-type Ca2+ channels more potently at depolarized
      membrane potentials, consistent with high affinity binding to the inactivated
      state. Nisoldipine (a DHP antagonist) blocks the smooth muscle channel more
      potently than the cardiac one, a phenomenon observed not only in native channels
      but also in expressed channels. We examined whether this tissue specificity was
      attributable to differences of inactivation in the two channel types. We
      expressed cardiac or smooth muscle alpha1C subunits in combination with beta2a
      and alpha2/delta subunits in human embryonic kidney cells, and used 2 mM Ca2+ as
      the permeant ion. This system thus reproduces the in vivo topology and charge
      carrier of the channels while facilitating comparison of the two alpha1C splice
      variants. Both voltage-dependent and isoform-specific sensitivity of 10 nM
      nisoldipine inhibition of the channel were demonstrated, with the use of -100 mV
      as the holding potential for fully reprimed channels and -65 mV to populate the
      inactivated state. Under drug-free conditions, we characterized fast inactivation
      (1-sec prepulses) and slow inactivation (3 min prepulses) in the two isoforms.
      Inactivation parameters were not statistically different in the two channel
      isoforms; if anything, cardiac channels tended to inactivate more than the smooth
      muscle channels at relevant voltages. Likewise, the voltage-dependent activation
      was identical in the two isoforms. We thus conclude that the more potent
      nisoldipine inhibition of smooth muscle versus cardiac L-type Ca2+ channels is
      not attributable to differences in channel inactivation or activation. Intrinsic,
      gating-independent DHP receptor binding affinity differences must be invoked to
      explain the isoform-specific sensitivity of the DHP block.

PMID- 9584218
TI  - A comparison of thermodynamic parameters for vinorelbine- and vinflunine-induced
      tubulin self-association by sedimentation velocity.
AB  - We present a comparison of the energetics of spiral formation for two vinca
      alkaloids: a novel difluorinated vinorelbine derivative 20',20'-difluoro-3',4'
      dihydrovinorelbine (F12158, or vinflunine) and the parent compound, vinorelbine.
      Vinca alkaloids are antineoplastic agents that halt cell division at metaphase by
      inhibiting microtubule assembly and inducing tubulin self-association into spiral
      aggregates. The overall affinities for tubulin of vincristine, vinblastine, and
      vinorelbine seem to correlate with their clinical doses, where vincristine with
      the highest overall affinity is used at the lowest doses. Doses of
      chemotherapeutic agents, however, also are determined by toxicities. In the
      physicochemical study described here, we used sedimentation velocity to compare
      vinorelbine- and vinflunine-induced self-association of porcine brain tubulin in
      the presence of 50 micro M GDP or 50 micro M GTP. Vinflunine demonstrates 3-16
      fold lower overall affinity for tubulin and induces smaller polymers compared
      with vinorelbine. Sedimentation velocity provides the only direct evidence to
      date that vinflunine is a tubulin-binding drug. Stopped-flow light scattering
      demonstrates the shortest relaxation times for polymer redistribution for
      vinflunine consistent with induction of the shortest spirals. Data collected at 5
      degrees, 15 degrees, 25 degrees, and 37 degrees show increasing 20,w values with
      increasing temperature and are consistent with an entropically driven process.
      These data are entirely consistent with our hypothesis that vinflunine is likely
      to result in reduced clinical neurotoxicity relative to vinorelbine, vinblastine,
      and vincristine.

PMID- 9584219
TI  - Characterization of the allosteric interactions between antagonists and amiloride
      analogues at the human alpha2A-adrenergic receptor.
AB  - The purpose of this study was to determine whether there is a well-defined
      allosteric site on the human alpha2A-adrenergic receptor. To explore this
      question, we examined the effects of amiloride analogues on the dissociation of
      [3H]yohimbine, [3H]rauwolscine, and [3H]RX821002. The dissociation data fitted
      well to an equation derived from the ternary complex allosteric model with
      amiloride analogue concentration and time as two independent variables. The
      estimated maximal increase in the [3H]yohimbine dissociation rate caused by the 5
      N-alkyl amilorides varied from 2-fold for the parent amiloride to 140- and 160
      fold for 5-(N, N-hexamethylene)-amiloride and 5-(N-ethyl-N-isopropyl)-amiloride,
      respectively. The calculated log affinities at the yohimbine-occupied receptor
      ranged from 1.75 for 5-(N-ethyl-N-isopropyl)-amiloride to 2.5 for 5-(N, N
      hexamethylene)-amiloride. The increase in affinity found at the yohimbine
      occupied receptor was not correlated with increase in size of the 5-N-alkyl side
      chain, in contrast to the situation found at the unoccupied receptor. The effect
      of competition between two amilorides on yohimbine dissociation also was
      explored. The data obtained were well fitted by the equation derived from the
      relevant model, with the off-rate increases caused by 5-(N, N-hexamethylene)
      amiloride being either decreased or increased by the competing amiloride analogue
      in line with predictions, and the parameters derived from the fits were in good
      agreement with those obtained in the above dissociation assays. Thus, the data
      are compatible with the amilorides competing at the one allosteric site on the
      alpha2A-adrenergic receptor and rules out the possibility that the amilorides are
      acting in a nonspecific fashion.

PMID- 9584220
TI  - Interferon-gamma-inhibitory oligodeoxynucleotides alter the conformation of
      interferon-gamma.
AB  - The aptamer mechanism of action involves the direct interaction of
      oligonucleotide with protein and is responsible for the biological effects of
      many pharmacologically active oligodeoxynucleotides. In the work reported here,
      we have determined the effects of aptamers on the secondary, tertiary, and
      quaternary structures of the proteins with which they interact using interferon
      gamma and the interferon-gamma-inhibitory aptamer oligonucleotide, 5'-GGG GTT GGT
      TGT GTT GGG TGT TGT GT, as a model system. CD, fluorescence spectroscopy studies,
      and antibody binding studies in this system demonstrate that the interferon-gamma
      inhibitory aptamer oligonucleotide causes significant changes in secondary and
      tertiary structures of interferon-gamma. These structural changes do not result
      in, or resemble, protein denaturation or aggregation, and the results suggest
      that aptamer oligodeoxynucleotides can significantly alter the structure of the
      proteins they interact with.

PMID- 9584221
TI  - The selectivity filter of the N-methyl-D-aspartate receptor: a tryptophan residue
      controls block and permeation of Mg2+.
AB  - A hallmark feature of N-methyl-D-aspartate (NMDA) receptors is their voltage
      dependent block by extracellular Mg2+. The structural basis for Mg2+ block is not
      fully understood. Although asparagine residues in the pore-forming M2 regions of
      NR1 and NR2 subunits influence Mg2+ block, it has been speculated that additional
      residues are likely to be involved. Here, we report the unexpected finding that a
      tryptophan residue in the M2 region of NR2 subunits controls Mg2+ block. An
      NR2B(W607L) mutation abolished block and greatly increased permeation of
      extracellular Mg2+. A similar effect was seen with a mutation at the equivalent
      residue in NR2A but not with mutations at the equivalent residue or adjacent
      residues in NR1. In NR2B, mutations that changed NR2B(W607) to asparagine (W607N)
      or alanine (W607A) also greatly reduced Mg2+ block, whereas mutations that
      changed W607 to the aromatic residues tyrosine (W607Y) or phenylalanine (W607F)
      had little or no effect on Mg2+ block. Furthermore, the W607L, W607N, and W607A
      mutants, but not the W607Y and W607F mutants, decreased Ba2+ permeability of NMDA
      channels. Thus, residue NR2B(W607) may be involved in binding of divalent
      cations, in particular Mg2+, through a cation-pi interaction with the electron
      rich aromatic ring of the tryptophan. We previously suggested that NR2B(W607) may
      contribute to the narrow constriction of the NMDA channel. A model is now
      proposed in which the M2 loop of NR2B is folded in such a way that NR2B(W607) is
      positioned at the narrow constriction, at a level similar to NR2B(N616) and
      NR1(N616), with these three residues forming a binding site for Mg2+.

PMID- 9584222
TI  - Kainate receptors exhibit differential sensitivities to (S)-5-iodowillardiine.
AB  - Characterization of the role of kainate receptors in excitatory synaptic
      transmission has been hampered by a lack of subtype-selective pharmacological
      agents. (S)-5-Iodowillardiine (IW), an analog of willardiine [(S)-1-(2-amino-2
      carboxyethyl)pyrimidine-2,4-dione], a heterocyclic amino acid found in Acacia and
      Mimosa seeds, was previously shown to be highly potent on native kainate
      receptors in dorsal root ganglion neurons. We examined the responses evoked by IW
      from recombinant homomeric and heteromeric kainate receptors expressed in human
      embryonic kidney 293 cells. IW potently elicited currents from glutamate receptor
      5 (GluR5)-expressing cells, but showed no activity on homomeric GluR6 or GluR7
      receptors. Co-expression of these receptor subunits with KA-2 subunits produced
      receptors that were weakly sensitive to IW. GluR5/KA-2 receptors had a higher
      EC50 value than homomeric GluR5 and exhibited a much faster recovery from
      desensitization. Finally, we found that the IW selectivity for GluR5 compared
      with GluR6 was determined by amino acid 721, which was previously shown to
      control alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate sensitivity of
      these kainate receptor subunits. The pharmacological selectivity and commercial
      availability of IW suggests that this compound may be of use in characterizing
      the molecular constituents of native kainate receptor responses.

PMID- 9584223
TI  - Agonist-induced up-regulation of alpha4beta2 nicotinic acetylcholine receptors in
      M10 cells: pharmacological and spatial definition.
AB  - Chronic nicotine up-regulates the number of high affinity nicotinic acetylcholine
      receptors (nAChRs) in mammalian brain. Here, we studied up-regulation of the
      nAChR composed of alpha4 and beta2 subunits in the M10 cell line by using
      [3H]epibatidine to measure nAChR in cells in situ and in membrane preparations.
      Cultures were exposed to drugs for 2 days before assay. All agonists up-regulated
      [3H]epibatidine binding sites with EC50 values typically 10-100-fold higher than
      their respective Ki values from competition binding assays. Maximum up-regulation
      ranged from 40% to 250% above control values. Maximally effective concentrations
      of the less efficacious agonists methylcarbamylcholine or (+/-)-epibatidine
      together with nicotine resulted in less up-regulation than that produced by
      nicotine alone, showing that they are partial up-regulatory agonists. The
      antagonists dihydro-beta-erythroidine, methyllycaconitine, d-tubocurarine,
      hexamethonium, decamethonium, and mecamylamine either failed to up-regulate
      [3H]epibatidine binding sites or up-regulated mildly at high concentrations. When
      tested at non-up-regulating concentrations, only d-tubocurarine significantly
      inhibited agonist-induced up-regulation; this inhibition seemed to be
      noncompetitive. Comparison of [3H]epibatidine displacement in intact M10 cells
      and membrane preparations by membrane-impermeant ligands indicated that 85% of
      [3H]epibatidine binding sites are intracellular. On chronic treatment with
      agonist, the proportion of surface receptors did not change significantly,
      indicating that most up-regulated [3H]epibatidine binding sites are internal.
      However, up-regulation is mediated at the cell surface because the impermeant
      ligand tetramethylammonium was as efficacious as nicotine in eliciting up
      regulation, and methylcarbamylcholine (i.e., impermeant but with low efficacy)
      blocked nicotine induced up-regulation. Thus, agonists elicit up-regulation
      (mainly of intracellular receptors) by interacting with cell surface nAChRs that
      are not compatible with either an active or high affinity desensitized
      conformation.

PMID- 9584224
TI  - Protean agonism at alpha2A-adrenoceptors.
AB  - The coupling of the endogenously expressed alpha2A-adrenoceptors in human
      erythroleukemia cells (HEL 92.1.7) to Ca2+ mobilization and inhibition of
      forskolin-stimulated cAMP production was investigated. The two enantiomers of
      medetomidine [(+/-)-[4-(1-[2, 3-dimethylphenyl]ethyl)-1H-imidazole]HCl] produced
      opposite responses. Dexmedetomidine behaved as an agonist in both assays (i.e. ,
      it caused Ca2+ mobilization and depressed forskolin-stimulated cAMP production).
      Levomedetomidine, which is a weak agonist in some test systems, reduced
      intracellular Ca2+ levels and further increased forskolin-stimulated cAMP
      production and therefore can be classified as an inverse agonist. A neutral
      ligand, MPV-2088, antagonized responses to both ligands. Several other,
      chemically diverse alpha2-adrenergic ligands also were tested. Ligands that could
      promote increases in Ca2+ levels and inhibition of cAMP production could be
      classified as full or partial agonists. Their effects could be blocked by the
      alpha2-adrenoceptor antagonist rauwolscine and by pertussis toxin treatment. Some
      typical antagonists such as rauwolscine, idazoxan, and atipamezole had inverse
      agonist activity like levomedetomidine. The results suggest that the alpha2A
      adrenoceptors in HEL 92.1.7 cells exist in a precoupled state with pertussis
      toxin-sensitive G proteins, resulting in a constitutive mobilization of
      intracellular Ca2+ and inhibition of cAMP production in the absence of agonist.
      This constitutive activity can be antagonized by inverse agonists such as
      levomedetomidine and rauwolscine. Levomedetomidine can be termed a "protean
      agonist" because it is capable of activating uncoupled alpha2-adrenoceptors in
      other systems and inhibiting the constitutive activity of precoupled alpha2
      adrenoceptors in HEL 92.1. 7 cells. With this class of compounds, the inherent
      receptor "tone" could be adjusted, which should provide a new therapeutic
      principle in receptor dysfunction.

PMID- 9584225
TI  - Bilateral cataract extraction with intraocular lens (IOL) implantation.

PMID- 9584226
TI  - Comments about bilateral simultaneous cataract surgery.

PMID- 9584227
TI  - Operating on cataracts in both eyes.

PMID- 9584228
TI  - Bilateral simultaneous cataract extraction.

PMID- 9584229
TI  - It began with a traumatic cataract.

PMID- 9584230
TI  - Criteria for authorship.

PMID- 9584231
TI  - Unfortunate discrepancies.

PMID- 9584232
TI  - The cataract extraction-refraction-implantation technique for IOL power
      calculation in difficult cases.

PMID- 9584233
TI  - Combining ablation zone diameters of different lasers for data analysis.

PMID- 9584234
TI  - Use of keratometry to assess corneal curvature.

PMID- 9584235
TI  - Consultation section. Cataract surgical problem.

PMID- 9584236
TI  - Corneal flap incision technique for sutureless cataract surgery.
AB  - A self-sealing incision technique for cataract surgery has been developed. It is
      appropriate for implantation of rigid-optic intraocular lenses (IOLs) up to 7.0
      mm. The incision is designed to meet the principle criteria of sutureless
      cataract surgery, such as optimal instrument handling, easy IOL implantation, and
      minimal postoperative patient care.

PMID- 9584237
TI  - Excimer laser phototherapeutic keratectomy for recurrent corneal erosion.
AB  - PURPOSE: To evaluate the outcome of excimer laser phototherapeutic keratectomy
      (PTK) for recurrent corneal erosion. SETTING: Laser Institute, Assay Harofeh
      Medical Center, Zerifin, Israel. METHODS: Twenty-three patients with a mean age
      of 50.56 years +/- 13.87 (SD) were referred between 1991 and 1995 for recurrent
      corneal erosion that did not respond to conservative treatment. All were treated
      by excimer laser PTK. Patients were interviewed and examined before and after
      treatment. RESULTS: Disease duration ranged from 2 months to 10 years. Frequency
      of attacks ranged from weekly to three to four times a year. Re-epithelialization
      of the cornea was established within an average of 3 days after PTK treatment.
      Follow-up was 12 to 60 months (mean 38.43 +/- 12.08 months). Nineteen (83%)
      patients were free of recurrences, and 3 had one recurrence treated successfully
      by patching. One patient who had two recurrences had a second PTK procedure and
      was symptom free for 14 months. No patient reported reduced visual acuity or
      quality. Postoperative best corrected visual acuity was unaltered in 21 eyes and
      improved in 2. There was no significant difference between preoperative and
      postoperative manifest refractions. CONCLUSION: Excimer laser PRK appears to be a
      safe and effective treatment for recurrent erosions of the cornea.

PMID- 9584238
TI  - Live-epikeratophakia for keratoconus.
AB  - PURPOSE: To assess the clinical feasibility of refractive live-epikeratophakia (L
      EPI) for early keratoconus to cap, rather than reverse, the ectatic cornea.
      SETTING: Eye Department, Martin-Luther-Hospital, Bochum, Germany. METHODS: Twenty
      seven consecutive cases with keratoconus stage I-II had L-EPI. Lenticules were
      obtained from eye-bank eyes. The lenticules were cut on the artificial anterior
      chamber bench of the Barraquer-Krumeich-Swinger set. Optical power was generated
      over refractive dies to achieve postoperative emmetropia. The lenticule was
      sutured into a peripherally undermined 7.0 mm trephination with a double-running
      torque suture. RESULTS: Re-epithelialization was complete within 4 to 6 days. In
      all but three cases that had corneal ulcers and experienced partial melting of
      tissue following severe neurodermatitis, all lenticules remained stable during
      the 10 year follow-up. The 1 month spherical equivalent remained almost stable
      over the entire follow-up. There was no sign of progression of keratoconus as
      induced myopia or astigmatism indicated by keratometry readings. Mean best
      spectacle-corrected visual acuity (BSCVA) was 0.45 (n = 27) preoperatively and
      0.19 (n = 25) at 1 week, 0.39 (n = 26) at 1 month, 0.53 (n = 20) at 6 months,
      0.58 (n = 13) at 1 year, and 0.64 (n = 8) at 2 years. Preoperative BCVA was
      achieved or improved in 13 eyes at 1 month. Postoperative astigmatism was < or =
      3.25 diopters. Neither rejection nor lenticule opacification was observed.
      CONCLUSIONS: Live-epikeratophakia is a safe and minimally invasive extraocular
      procedure suitable for keratoconus stage I-II. Progression of keratoconus may be
      arrested. If unsuccessful, the procedure is complementable and there is no
      interference with a later penetrating keratoplasty.

PMID- 9584240
TI  - Radial keratotomy learning curve using the American technique.
AB  - PURPOSE: To delineate the learning curve for a beginning refractive surgeon using
      the centrifugal (American) technique. SETTING: Naval Medical Center, San Diego,
      California, USA. METHODS: The first 100 radial keratotomy (RK) cases (51
      patients) of one surgeon, divided into five sequential groups of 20, were
      retrospectively reviewed. All patients had RK using the American technique.
      Emmetropia was the goal in all patients. Groups were compared with respect to
      preoperative refractive status, age, sex, and outcome. Outcomes analysis included
      visual acuity, refractive error, complications, and enhancement rates. Data were
      reviewed preoperatively and 1 and 3 months postoperatively. RESULTS: All five
      groups were age and sex matched. There was no difference in preoperative
      refractive error among the five groups. Sequential improvement in early
      postoperative refractive error from a mean of -1.73 diopters (D) +/- 1.00 (SD)
      (first 20) to 0.45 +/- 0.55 D (last 20) (P < .001) and decreased enhancement
      rates from 50% (first 20) to 0% (last 20) (P = .002) were statistically
      significant. Visual acuity at 1 month was 20/40 or better in 47% of patients in
      Group 1 (first 20), whereas all patients in Group 5 (last 20) had an acuity
      better than 20/40 (P < .001). There was no significant difference in complication
      rates among the five groups. CONCLUSION: The results of RK using the American
      technique can improve significantly with surgeon experience. Enhancement rates
      decreased with experience, and there was no difference in complication rates
      during the learning period of one surgeon.

PMID- 9584239
TI  - Treatment of topographic central islands following refractive surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of using central reablation to treat
      topographic central islands following photorefractive keratectomy (PRK), myopic
      keratomileusis in situ, and laser in situ keratomileusis (LASIK). SETTING:
      Department of Ophthalmology, Stanford University School of Medicine, Stanford,
      and Jules Stein Eye Institute, Los Angeles, California, USA. METHODS: Central
      reablation was performed on eight eyes with clinically significant topographic
      central islands after refractive surgery. Two eyes developed central islands
      after PRK, five eyes after LASIK, and one eye after myopic keratomileusis in
      situ. A clinically significant topographic central island was defined as an area
      of steepening of at least 3.0 diopters by at least 1.5 mm in diameter documented
      by computerized videokeratography. Reablation was tailored to each eye based on
      the diameter and power of the topographic central island using the Munnerlyn
      formula. RESULTS: All eyes experienced a reduction or elimination of the
      topographic central islands following central reablation. Six eyes experienced an
      improvement in uncorrected visual acuity, and all eyes returned to within one
      line of their preoperative level of best spectacle-corrected visual acuity 1
      month after the procedure. CONCLUSION: Topographic central islands following PRK,
      myopic keratomileusis in situ, and LASIK can be effectively treated using the
      excimer laser. Poor predictability of the refractive effect of central reablation
      may be the limitation of this treatment modality.

PMID- 9584241
TI  - Comparison of surgically induced astigmatism after sutureless temporal clear
      corneal and scleral frown incisions.
AB  - PURPOSE: To compare the corneal astigmatic changes induced by clear corneal
      incisions with those induced by scleral tunnel frown incisions., both from a
      temporal approach, in sutureless cataract surgery. SETTING: Department of
      Ophthalmology, College of Medicine, National Cheng Kung University, Tainan,
      Taiwan, Republic of China. METHODS: This prospective study comprised 120 eyes
      divided into two groups of 60 each based on incision type. All patients had
      examinations with an autokeratometer preoperatively and 1 week and 1, 3, and 6
      months postoperatively. RESULTS: Simple subtraction of the scalar analysis in
      each group showed minimal astigmatic changes; however, the standard deviation of
      astigmatic change was greater in the clear corneal incision group. The mean
      vector analysis of surgically induced astigmatism in the scleral frown incision
      group was 0.;69, 0.75, 0.72, and 0.61 diopter (D) at 1 week and 1, 3, and 6
      months, respectively. In the clear corneal incision group, it was 1.55, 1.12,
      0.93, and 0.92 D at the same intervals. In the scleral frown incision group,
      Naeser's polar value also showed minimal changes in polar astigmatism throughout
      the study; in the clear corneal incision group, it showed a mean with-the-rule
      (WTR) astigmatic shift of +0.73, +0.22, +0.13, and +0.08 D at 1 week and 1, 3,
      and 6 months, respectively. CONCLUSION: Corneal stability was achieved with
      minimal astigmatic change 1 week after scleral frown incisions, while clear
      corneal incisions induced greater WTR astigmatism with delayed stabilization 1 to
      3 months postoperatively.

PMID- 9584243
TI  - Ultrastructure of clear corneal incisions. Part I: Effect of keratomes and
      incision width on corneal trauma after lens implantation.
AB  - PURPOSE: To examine the ultrastructure of clear corneal incisions (CCIs)
      performed with diamond keratomes and steel blades as well as the corneal trauma
      after implantation of a foldable intraocular lens (IOL) through two incision
      widths. SETTING: University Eye Clinic and Institute of Histology and Embryology
      II, University of Vienna, Austria. METHODS: Twenty-four human cadaver eyes
      without prior ocular surgery were obtained from the University Eye Bank, Vienna.
      Single-plane CCIs were performed with 3.0 and 3.2 mm Alcon steel blades and with
      a 3.0 mm Huco diamond keratome. The AMO PhacoFlex II lens was implanted with a
      Fine II folder. During the entire procedure, the eye pressure was kept between 26
      and 30 mm Hg by infusing balanced salt solution into the anterior chamber.
      Specimens were prepared for light microscopy, transmission electron microscopy,
      and scanning electron microscopy according to standard procedures. RESULTS: The
      diamond keratome produced cleaner cuts than the steel blade. After IOL
      implantation, 3.0 mm steel blade incisions exhibited extensions at their lateral
      ends. Within these extensions, the collagen lamellae were displaced and torn.
      This was not true with 3.2 mm tunnels. Because of the thickness of a 3.0 mm
      diamond keratome, the extent of corneal trauma was between that found with 3.0
      and 3.2 mm steel keratome tunnels. CONCLUSIONS: Implantation of the SI-30 through
      3.0 mm CCIs produced by the steel blade led to more severe corneal trauma than
      implantation through 3.2 mm steel blade incisions or 3.0 mm diamond keratome
      incisions. Thus, IOL implantation through incisions that are too small
      intensifies corneal trauma.

PMID- 9584242
TI  - Is there a difference in incision healing based on location?
AB  - PURPOSE: To determine whether there is a difference in the healing process
      between incisions that begin in avascular region and those that begin in vascular
      region. SETTING: Wills Eye Hospital, Philadelphia, Pennsylvania, and Kresge Eye
      Institute, Detroit, Michigan USA. METHODS/MATERIALS: Feline evaluations were
      conducted at two sites (one evaluation at each site). Eyes in both evaluations
      were grouped by incision location: avascular (clear corneal) incisions or
      vascular (limbal) incisions. A series of postoperative examinations were
      conducted in each group of both evaluations that included slitlamp examination,
      measurements of external pressure and incision stability, and histological
      analysis. RESULTS: All limbal incisions were stable 7 days after surgery.
      Histological analyses in both evaluations showed a difference in tissue response
      between clear corneal and limbal incisions; the limbal incisions had an early
      fibroblastic response and the clear corneal, a delayed response. CONCLUSION: The
      predominant factors in incision healing and stability were incision geometry,
      architecture, and location. Endothelial pump action was effective in removing
      fluid but was not effective in incision stability. Histological analyses
      confirmed that starting incisions in the vascular region (limbus) resulted in a
      fibroblastic response that enhanced incision stability and allowed rapid incision
      healing within 7 days postoperatively compared with the 60 days healing time
      required for incisions started in the avascular region (cornea).

PMID- 9584244
TI  - Ultrastructure of clear corneal incisions. Part II: Corneal trauma after lens
      implantation with the Microstaar injector system.
AB  - PURPOSE: To examine the ultrastructure of clear corneal incisions (CCIs) after
      implantation of a plate-hepatic intraocular lens (IOL) with the Microstaar
      injector system through two incision widths. SETTING: University Eye Clinic and
      Institute of Histology and Embryology II, University of Vienna, Austria. METHODS:
      Fourteen human cadaver eyes without prior ocular surgery were obtained from the
      University Eye Bank, Vienna. Single-plane CCIs were performed with 3.0 and 3.2 mm
      steel keratomes. Using the Microstaar injector system, a foldable silicone plate
      haptic IOL (23 diopters) was implanted in the anterior chamber. During the entire
      procedure, the eye pressure was kept between 26 and 30 mm Hg by infusing balanced
      salt solution into the anterior chamber. Specimens for light microscopy and
      scanning electron microscopy were prepared according to standard procedures.
      RESULTS: After IOL implantation, the 3.0 mm steel blade incisions exhibited
      distinct distensions at their lateral ends. Adjacent to these distensions, the
      collagen lamellae were pressed apart, displaced, and torn. In 3.2 mm tunnels, the
      corneal trauma at both lateral ends was considerably less severe. These incisions
      also showed a better primary adaptation of the wound lips after implantations.
      CONCLUSIONS: Implantation performed with the Microstaar injector system through
      3.0 mm steel blade CCIs led to considerably more severe corneal trauma than
      implantation through 3.2 mm incisions.

PMID- 9584245
TI  - Histological and ultrastructural study of corneal tunnel incisions using diamond
      and steel keratomes.
AB  - PURPOSE: To study the morphology of corneal tunnel incisions using diamond and
      steel keratomes. SETTING: Department of Ophthalmology, University of Giessen,
      Germany. METHODS: Corneal tunnel incisions were performed in six human cadaver
      eyes using three types of diamond keratomes and a steel keratome. The incision
      profile and morphology were evaluated and compared using light and scanning
      electron microscopy. RESULTS: The steel keratome caused more disruption of
      corneal stromal tissue, while the diamond keratomes produced a more regular,
      smoother incision. The dissecting incision resulted in a smoother surface of cut
      stromal tissue than the stab incision. CONCLUSIONS: The high quality of corneal
      tunnel incisions produced with diamond keratomes is the result of their
      exceptional sharpness, which may have a beneficial effect on wound healing.

PMID- 9584246
TI  - Limbal relaxing incisions with cataract surgery.
AB  - PURPOSE: To evaluate the effectiveness of limbal relaxing incisions (LRIs) for
      correcting corneal astigmatism during cataract surgery. SETTING: Cullen Eye
      Institute, Houston, Texas, USA. METHODS: In 12 eyes of 11 patients, cataract
      surgery was combined with LRIs. The LRIs were made according to a modified Gills
      nomogram and were based on preoperative corneal astigmatism determined with
      standard keratometry and computerized videokeratography (EyeSys Corneal Analysis
      System Version 3.2). RESULTS: The mean preoperative keratometric cylinder was
      2.46 +/- 0.81 diopters (D). At 1 month postoperatively, mean arithmetic reduction
      in keratometric cylinder was 1.12 +/- 0.74 D, and the with-the-wound (WTW) change
      (calculated by Holladay, Cravy, Koch vector analysis formula) was -0.70 +/- 0.44.
      From 1 day to 1 month postoperatively, there was 0.55 D of WTW regression with
      minimal change in the mean cylindrical axis. There were no overcorrections.
      CONCLUSION: Limbal relaxing incisions are a practical, simple, and forgiving
      approach to the correction of astigmatism during cataract surgery.

PMID- 9584247
TI  - Three year prospective, randomized evaluation of intraocular lens implantation
      through 3.2 and 5.5 mm incisions.
AB  - PURPOSE: To compare the long-term clinical results of two small incision cataract
      surgery procedures. SETTING: Seven centers in Japan. METHODS: Two hundred eyes
      were randomly assigned to receive a silicone intraocular lens (IOL) through a 3.2
      mm incision or a poly(methyl methacrylate) (PMMA) IOL through a 5.5 mm incision.
      Except for incision size and implantation technique, the surgical methods were
      identical. Uncorrected and corrected visual acuity, keratometry, flare-cell
      intensity, specular microscopy, and neodymium:YAG (Nd:YAG) laser posterior
      capsulotomy rate were analyzed up to 3 years after surgery. RESULTS: Eyes in the
      3.2 mm incision group had significantly better uncorrected and corrected visual
      acuity in the early postoperative period and lower aqueous flare intensity
      immediately after surgery, but these differences disappeared after the first
      postoperative month. However, surgically induced astigmatism was significantly
      less in the 3.2 mm incision group than in the 5.5 incision group throughout the
      study. The Nd:YAG laser capsulotomy rate was higher in the silicone IOL group
      (23.5% at 3 years postoperatively) than in the PMMA IOL group (18.4%) but the
      difference was not statistically significant. CONCLUSION: Smaller incision
      cataract surgery led to early recovery of visual function in the short term and
      less induced astigmatism in the long term.

PMID- 9584248
TI  - Effect of superior and temporal clear corneal incisions on astigmatism after
      sutureless phacoemulsification.
AB  - PURPOSE: To evaluate the effect of superior and temporal clear corneal incisions
      on astigmatism after sutureless, small incision phacoemulsification. SETTING:
      World Eye Hospital, Istanbul, Turkey. METHODS: This prospective study evaluated
      40 eyes of 20 patients with cataract having bilateral, sutureless, small incision
      phacoemulsification by the same surgeon. A superior clear corneal incision was
      used in all right eyes and a temporal clear corneal incision in all left eyes.
      Mean preoperative astigmatism was 0.63 diopter (D) +/- 0.21 (SD) and 0.65 +/-
      0.20 D, respectively. Mean patient age was 66.45 years. Patients were examined
      preoperatively and 1 day, 1 week, and 1 and 3 months postoperatively. RESULTS:
      Three months postoperatively, mean astigmatism was 1.60 +/- 0.37 D in the
      superior incision group and 0.83 +/- 0.19 D in the temporal incision group.
      Induced astigmatism calculated by vector analysis was 1.44 +/- 0.31 D and 0.62 +/
      0.28 D, respectively. The temporal incision group had significantly lower
      astigmatism at all follow-ups (P = .000). CONCLUSION: Upper lid pressure on the
      superior corneal incisions led to fluctuating, against-the-rule astigmatism that
      was significantly higher than that induced by temporal incisions.

PMID- 9584249
TI  - Astigmatism induced by intrastromal corneal suture after small incision
      phacoemulsification.
AB  - PURPOSE: To evaluate the course of astigmatic evolution and complications after
      clear corneal incisions using an intrastromal corneal suture. SETTING: Instituto
      Oftalmologico de Alicante, University of Alicante, Spain. METHODS: Eighty eyes of
      62 patients had endocapsular phacoemulsification. A foldable intraocular lens was
      implanted through a 4.0 mm clear corneal incision. A 10-0 nylon intrastromal
      corneal suture was used in all eyes. Change sin corneal astigmatism were
      calculated by vector analysis; follow-up was 6 months. Early and late suture
      related complications were also evaluated. RESULTS: Mean induced cylinder was
      1.25 diopters (D) +/- 1.24 (SD) with the wound 1 day postoperatively and 0.19 +/-
      0.81 D against the wound at 6 months. There were no incision- or suture-related
      complications postoperatively. CONCLUSION: Use of the intrastromal corneal suture
      led to astigmatically neutral closure of multiplanar corneal incisions.

PMID- 9584250
TI  - Postoperative inflammation after clear corneal and sclerocorneal incisions.
AB  - PURPOSE: To compare two standard small incision techniques for cataract surgery-
      clear corneal incision and sclerocorneal incision--with regard to postoperative
      disturbance of the blood-aqueous barrier (BAB). SETTING: Department of
      Ophthalmology, University of Vienna, Austria. METHODS: This prospective
      comparative study comprised 108 eyes with senile cataract. A clear corneal tunnel
      incision was made in 53 eyes and a sclerocorneal incision with tunnel preparation
      in 55. All other surgical procedures and postoperative medication were
      standardized. Postoperative BAB disruption was measured with a laser flare-cell
      meter (Kowa FC 1000) in an undilated pupil on 1, 3, 7, 14, 28, 60, and 90 days
      postoperatively. The values were compared using a two-sided t-test. RESULTS: In
      both groups, flare and cell values were highest on the first postoperative day.
      They gradually declined but without recovery of preoperative flare values on day
      28. At no time was there a noticeable between-group difference in mean cell and
      flare values except for flare at day 14 (P = .04). CONCLUSION: Postoperative
      trauma, measured by the BAB disturbance, was equally low after clear corneal and
      sclerocorneal incisions.

PMID- 9584251
TI  - B-mode-guided vector-A-mode versus A-mode biometry to determine axial length and
      intraocular lens power.
AB  - PURPOSE: To compare prospectively the reproducibility and accuracy of B-mode
      guided biometry with those of A-scan biometry using a conventional A-mode probe
      to calculate intraocular lens (IOL) power. SETTING: Department of Ophthalmology,
      Hotel-Dieu de Paris, France. METHODS: The axial length (AL) in 87 eyes of 72
      candidates for cataract surgery was determined by B-mode-guided vector-A-mode and
      A-mode biometry using an Ophthascan S Ultrasound imager. Patients were assigned
      to one of two groups based on the B-mode biometry: nonmyopic (AL < 24.5 mm; n =
      54) or myopic (AL > 24.5 mm; n = 33). Postoperative refractive results were
      compared with attempted values. RESULTS: Mean AL variance was significantly
      greater when using the A-mode than the B-mode: 0.157 mm +/- 0.260 (SD) versus
      0.015 +/- 0.018 mm in the myopic group (P < .001) and 0.024 +/- 0.024 +/- 0.045
      versus 0.009 +/- 0.011 mm in the nonmyopic group (P < .001). More eyes having B
      mode biometry achieved a final refraction within +/- 0.50 diopter (D) of the
      attempted refraction (63 and 43%, respectively; P < .05). No deviation greater
      than 1.60 D was observed with the B-mode in the myopic or nonmyopic group. Three
      cases with a such a deviation (up to 2.24 D) would have been observed had A-mode
      based biometry been chosen for the IOL power calculation. In the myopic group,
      attempted postoperative refraction was within +/- 0.50 D in 78% of eyes having B
      mode biometry compared with 65% having A-mode. This difference was not
      statistically significant. CONCLUSION> These results suggest that the
      reproducibility and accuracy of AL measurements are significantly better with B
      mode-guided A-mode biometry than with A-mode biometry in myopic and nonmyopic
      eyes.

PMID- 9584252
TI  - Resistance of the human posterior lens capsule and zonules to disruption.
AB  - PURPOSE: To determine the resistance of the human posterior lens capsule and
      zonules to disruption during cataract surgery. SETTING: Wet lab at Walkergate
      Hospital, Newcastle upon Tyne, England. METHOD: Human donor eyes were obtained
      after removal of a corneoscleral disc. Lens extraction was performed by an
      extracapsular technique leaving an intact capsular bag. The resistance of the
      zonules and posterior capsule to disruption by aspiration was measured in each
      eye, and the resistance of the zonules to damage from direct mechanical stretch
      was determined. RESULTS: Posterior capsules tolerated a median suction pressure
      of 200 mm Hg (range 150 to 300 mm Hg) before disruption. Values for female eyes
      were slightly greater than for male; no significant correlation with age was
      shown. The zonular fibers tolerated a median suction pressure of 200 mm Hg (range
      150 to 300 mm Hg). The median mechanical zonular stretch tolerance was 3.00 mm
      (range 2.75 to 4.00 mm). No significant correlation was found between zonular
      suction tolerance or stretch tolerance and sex or between suction tolerance and
      age, but a negative relationship was noted between maximum tolerated stretch and
      age. CONCLUSION: Setting the maximum aspiration pressure during
      irrigation/aspiration to 150 mm Hg should help prevent capsular or zonular
      rupture. If more powerful aspiration is required, it should be used with great
      care so as not to engage the capsule.

PMID- 9584253
TI  - Tensile strength of lens capsules in eye-bank eyes.
AB  - PURPOSE: To measure the tensile strength of the anterior and posterior lens
      capsules in eye-bank eyes and study the tensile strength of capsules dehydrated
      with hypertonic glucose solution. SETTING: Tongren Hospital, Beijing, China.
      METHODS: The in situ anterior and posterior capsules of 35 eye-bank eyes (Group
      1) donated by healthy men aged 20 to 40 years (mean 27.1 years) were measured
      with a biomembrane strength device. Sixteen eyes (Group 2), from donors aged 20
      to 37 years (mean 27.0 years) and similar to those in Group 1, were measured in
      the same way after the anterior and posterior capsules were exposed to glucose
      50% solution for 15 minutes. RESULTS: In Group 1, anterior and posterior capsule
      strength was 6.269 +/- 1.118 and 3.755 +/- 0.835 g, respectively (P < .01), and
      the correlation between the tensile strength of the anterior and posterior
      capsules was statistically significant (r = .94; P < .001). In Group 2, the
      strength of the capsules increased to 9.024 +/- 0.586 and 4.424 +/- 0.761 g,
      respectively, a finding that was statistically significantly different from that
      in Group 1 (P < .01 and .05, respectively. CONCLUSION: The tensile strength of
      the anterior capsule was stronger than that of the posterior capsule under the
      experimental conditions. Glucose 50% solution has the potential to increase the
      tensile strength of anterior and posterior capsules.

PMID- 9584254
TI  - Relationship between lens and capsular bag size.
AB  - PURPOSE: To measure the size of the lens and the empty capsular bag and evaluate
      the relationship between them. SETTING: Iladevi Cataract & IOL Research Centre,
      Ahmedabad, India. METHODS: In 46 eye-bank eyes, the equatorial diameter of the
      lens was measured after a corneoscleral button and the iris were removed. Empty
      capsular bag diameter was measured after extracapsular cataract extraction
      through an intact capsulorhexis. RESULTS: Mean lens size was 10.20 mm +/- 0.38
      (SD) and mean capsular bag size, 10.38 +/- 0.35 mm. The difference between the
      size of the lens and that of the empty capsular bag varied from 0 to 0.50 mm
      (mean 0.20 +/- 0.17 mm). Lenses measuring less than 10.25 mm in diameter showed
      an increase of 0.25 mm while lenses larger than 10.25 mm showed an increase of
      0.09 mm. CONCLUSION: Lens size was larger in our population than in previous
      studies. The increase in the empty capsular bag size was related to initial lens
      size.

PMID- 9584255
TI  - Practice styles and preferences of ASCRS members--1997 survey.
AB  - A survey of the practice styles and preferences of members of the American
      Society of Cataract and Refractive Surgery with a United States ZIP code was
      performed in September 1997. Approximately 29% (1441) of the 5000 questionnaires
      mailed were returned by the November cut-off date. Three main profile questions
      were used to cross-tabulate data: age of the ophthalmologist, geographic
      location, and volume of cataract surgery per month. Current data were compared
      with data in previous annual surveys.

PMID- 9584256
TI  - Postoperative Rhizopus scleritis in a diabetic man.
AB  - A 50-year-old diabetic man developed necrotizing scleritis with adjacent
      keratitis 4 weeks after uncomplicated cataract extraction and intraocular lens
      implantation through a scleral tunnel incision. Cultures of the necrotic sclera
      grew Rizopus species. Severe destruction of the globe ensued despite topical,
      subconjunctival, and intravenous amphotericin B, in combination with hyperbaric
      oxygen therapy. Histopathological examination of the enucleated globe was
      consistent with Rhizopus infection. One year later, the patient was well without
      signs of recurrence.

PMID- 9584257
TI  - Piggyback minus-power lens implantation in keratoconus.
AB  - A 53-year-old man with keratoconus and an axial length of 32.59 mm had cataract
      extraction by phacoemulsification. The Holladay II formula called for -14.00
      diopters (D) of power. Two negative-power intraocular lenses (IOLs) were
      implanted to optimize visual results. A 1 day postoperative refraction of +1.50 D
      sphere necessitated an exchange of the anterior IOL. Six days after the exchange,
      the patient had a refraction of -1.25 D sphere and best corrected visual acuity
      of 20/50.

PMID- 9584258
TI  - Piggyback intraocular lens implantation.
AB  - Piggyback intraocular lenses (IOLs), used in eyes requiring high IOL powers, are
      generally implanted in the capsular bag. Proper position of the IOL loops is,
      however, an unresolved issue. In this case of piggyback implantation in both eyes
      of a patient, the loops of the second IOL were positioned at an axis between 45
      and 60 degrees away from those of the first IOL. Six weeks after surgery, the
      loops in both eyes had rotated into a parallel position.

PMID- 9584259
TI  - Pregnancy in a woman with maple syrup urine disease.
AB  - We present the favourable outcome of a pregnancy in a woman with maple syrup
      urine disease. Keeping the maternal plasma levels of the branched-chain amino
      acids between 100 and 300 mumol/L is compatible with delivery of a normal infant.
      Leucine tolerance increased progressively from the 22nd week of gestation from
      350 to 2100 mg/day. The risk of metabolic decompensation in the postpartum period
      can be minimized by careful monitoring of the mother after delivery.

PMID- 9584260
TI  - Intravenous immune globulin in lysinuric protein intolerance.
AB  - In addition to systemic manifestations with skeletal, pulmonary, renal, and
      haematological signs, lysinuric protein intolerance (LPI), a membrane transport
      defect of cationic amino acids, is often complicated by severe life-threatening
      immunological manifestations. A 10-year-old boy with LPI who exhibited a severe
      systemic immunohaematological disease is described here. This patient showed
      cutaneous lesions similar to the subacute form of systemic lupus erythematosus,
      severe anaemia and dysproteinaemia, and a marked reduction of circulating T
      lymphocytes, mainly the CD4+ cells. In vitro bone marrow cell culture studies
      showed that addition of patient's serum induced macrophage proliferation and
      inhibited erythroid progenitor cell growth. Treatment with high-dose intravenous
      immune globulin resolved most of the clinical and laboratory abnormalities.

PMID- 9584261
TI  - Varicella and varicella immunity in patients with lysinuric protein intolerance.
AB  - Two patients with lysinuric protein intolerance (LPI) had near-fatal generalized
      varicella infection with severe interstitial pneumonitis, hepatitis, decreased
      platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in
      anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and
      ferritin concentration, which in patients with LPI in normal circumstances exceed
      the upper reference values 3-folds to 10-fold, increased to > 10,000 U/L and >
      10,000 micrograms/L, respectively. The patients were treated with fresh frozen
      plasma, red-cell transfusions and intravenous acyclovir for 14 days, and
      recovered clinically in a month. Retrospectively, 3 of the 32 other known Finnish
      patients with LPI had had varicella infection that had been more severe than that
      in the other children in the family or in subjects in the neighbourhood and had
      led to hospital admission. Varicella antibodies were measured in 24 patients; 5
      had no antibodies and 5 had very low antibody titres. Primary vaccination of
      three patients with living varicella vaccine increased antibody titres measurably
      in one patient. We suggest that patients with LPI who have no varicella zoster
      antibodies should be treated with acyclovir if exposed to varicella and should be
      (re)vaccinated against chickenpox.

PMID- 9584262
TI  - The heart and pericardial effusions in CDGS-I (carbohydrate-deficient
      glycoprotein syndrome type I).
AB  - Pericardial effusions were found in 6 of 10 children with carbohydrate-deficient
      glycoprotein syndrome type I (CDGS-I). In three cases pericardectomy was
      necessary. Blood concentrations of several glycoproteins and albumin were low.
      Similar abnormal isoforms of four glycoproteins were found in blood (B) and
      pericardial fluid (PF). There was a significant negative correlation between the
      mean concentration ratio PF/B and the molecular mass (MW) of 11 proteins. For
      proteins with MW < 100 kDa there were significant correlations in the controls,
      but not in the patients, between the PF/B ratio and both the MW and the sialic
      acid contents in the (glyco-)proteins. The pericardium exhibited focal mixed
      inflammatory changes with mesothelial proliferation, with widened endoplasmic
      reticulum and flocculent and/or lamellated material. Damage to a pericardial
      protein barrier is suggested to be involved in pericardial effusion in CDGS-I.

PMID- 9584264
TI  - Improvement in exercise tolerance in isovaleric acidaemia with L-carnitine
      therapy.
AB  - The effect of 4 weeks' treatment with oral-L-carnitine (100 mg/kg per day) on
      carnitine status and metabolic parameters during an incremental ramp exercise
      test in a 12-year-old girl with isovaleric acidaemia was examined to determine
      its possible therapeutic role. The maximum work rate achieved increased from 110
      to 120 watts; oxygen consumption at anaerobic threshold from 600 to 800 L/min;
      peak oxygen consumption from 1270 to 1450 L/min; and oxygen pulse, a measure of
      cardiac output, from 7.0 to 8.1 L/beat. These changes were associated with
      increases in plasma and urinary free and acyl carnitine concentrations but no
      change in physical activity. This observed effect of L-carnitine on exercise
      performance may be on cardiac or skeletal muscle function or both. We conclude
      that, in this single patient with isovaleric acid-aemia, L-carnitine
      supplementation had objective benefits and further studies on more patients are
      warranted.

PMID- 9584263
TI  - Executive function in treated phenylketonuria as measured by the one-back and two
      back versions of the continuous performance test.
AB  - The executive dysfunction hypothesis in treated phenylketonuria was investigated
      by means of the one-back and two-back versions of the continuous performance
      test. Eleven non-retarded, primary school-age children with classical
      phenylketonuria who had been treated early and continuously were
      indistinguishable from healthy, matched controls on the measures and test
      performance was not predicted by historical or concurrent plasma phenylalanine
      concentrations. Mean lifetime phenylalanine concentrations for the
      phenylketonuric subjects were within ranges currently recommended as dietary
      optima in the United Kingdom. The negative neuropsychological test findings add
      weight to the rationale for this policy.

PMID- 9584265
TI  - Two new mutations in the 3' coding region of the glycogen debranching enzyme in a
      glycogen storage disease type IIIa Ashkenazi Jewish patient.
AB  - Glycogen storage disease type III (GSD III) is an autosomal recessive disease
      caused by the deficiency of glycogen debranching enzyme (AGL). We report the
      finding of two new mutations in a GSD IIIa Ashkenazi Jewish patient. Both
      mutations are insertion of an adenine into a stretch of 8 adenines towards the 3'
      end of the coding region, one at position 3904 (3904insA) in exon 30, the second
      at position 4214 (4214insA) in exon 32. The mutations cause frameshifts and
      premature terminations of the glycogen debranching enzyme, the first causing a
      frameshift at amino acid 1304, the second causing a frameshift at amino acid 1408
      of the total of 1532. These mutations demonstrate the importance of the 125 amino
      acids at the carboxy-terminus of the debrancher enzyme for its activity and
      support the suggestion that the putative glycogen binding domain is located in
      the carboxy-terminus of the AGL. The mutations cause distinctive single-strand
      conformation polymorphism (SSCP) patterns enabling easy detection.

PMID- 9584267
TI  - Primary adrenal insufficiency in a child with a mitochondrial DNA deletion.
AB  - Mitochondrial disorders can affect any organ system, but certain tissues, such as
      skeletal muscle, heart, and brain are more susceptible to oxidative
      phosphorylation defects because of their high energy requirements.
      Endocrinological manifestations, especially diabetes mellitus, are common but
      they rarely dominate the clinical picture. We describe a 5-year-old girl who died
      of primary adrenal insufficiency with a mitochondrial disease. Biochemical
      studies in muscle showed decreased respiratory chain enzyme activities. We
      detected a novel 7.0 kb mtDNA deletion in muscle form the proband, but not in her
      mother's white blood cells. Our findings further enlarge the spectrum of clinical
      presentation associated with mitochondrial DNA deletions.

PMID- 9584266
TI  - Niemann-Pick disease type C and defective peroxisomal beta-oxidation of branched
      chain substrates.
AB  - An 18-month-old infant presented with hypotonia, motor delay, hepatosplenomegaly,
      rickets and steatorrhoea. Biochemical investigations revealed typical features of
      Niemann-Pick disease type C. In addition, there was evidence of defective
      peroxisomal beta-oxidation of branched-chain substrates (3 alpha, 7 alpha, 12
      alpha-trihydroxycholestanoic acid and pristanic acid). The steatorrhoea and fat
      soluble vitamin malabsorption responded well to bile acid therapy. Possible
      causes for the double defect are considered.

PMID- 9584268
TI  - A novel mutation found in an adrenoleukodystrophy patient who underwent bone
      marrow transplantation.
AB  - We identified a novel mutation, L322P, in a patient with X-linked
      adrenoleukodystrophy (ALD) who underwent bone marrow transplantation (BMT). An
      identification of the ALD gene mutation enabled us to employ an approach not
      dependent on the use of radioisotopes for detecting mixed chimerism. This assay
      could show more than 99.0% of the patient's peripheral white blood cells were
      replaced by the donor's cells.

PMID- 9584269
TI  - Lysosomal enzyme activities in serum and leukocytes from patients with
      carbohydrate-deficient glycoprotein syndrome type IA (phosphomannomutase
      deficiency).
AB  - From 10 patients with carbohydrate-deficient glycoprotein (CDG) syndrome due to
      phosphomannomutase (PMM) deficiency, out of 10 lysosomal enzymes, 7 enzyme
      activities were measured in serum and 9 in leukocytes. In serum there was a 2
      fold to 4-fold increase in activity of beta-glucuronidase, beta-hexosaminidase,
      beta-galactosidase, and arylsulphatase A. In leukocytes, however, several enzymes
      had reduced activity, particularly alpha-fucosidase, beta-glucuronidase and alpha
      mannosidase. These abnormalities could result from missorting, defective reuptake
      and/or reduced stability of the enzymes due to the defective glycosylation.

PMID- 9584270
TI  - Mitochondrial deletion in a boy with growth hormone deficiency mimicking cerebral
      palsy.

PMID- 9584271
TI  - Late-infantile 3-methylcrotonyl-CoA carboxylase deficiency presenting as global
      developmental delay.

PMID- 9584272
TI  - Maple syrup urine disease: nutritional management by intravenous
      hyperalimentation and uneventful course after surgical repair of dislocation of
      the hip.

PMID- 9584273
TI  - Impaired DNA synthesis in dermal fibroblasts from Zellweger syndrome patients.

PMID- 9584274
TI  - Pathogenesis of different clinical outcomes in spite of identical genotypes and
      comparable blood phenylalanine concentrations in phenylketonurics.

PMID- 9584275
TI  - Biochemical studies on proteins from cheese whey and blood plasma by-products.
AB  - Efforts have been done to recover proteins from waste liquors rich in protein in
      a soluble form. Cheese whey and animal bloods are by-products from the
      manufacture of cheese and meat. It contains a variety of proteins which can be
      reclaimed. The efficiency of protein precipitation from the sweet-cheese whey by
      the use of hydroxyethyl cellulose (HEC) was similar to that precipitated by the
      use of carboxymethyl cellulose (CMC). Both are greater than that precipitated by
      trichloro acetic acid. The same results of the efficiency of precipitation were
      attained when the plasma was precipitated. It was found that cheese-whey protein
      HEC-complex and plasma protein-HEC-complex contain a large amount of essential
      amino acids. Electrophoretic separation of whey protein complex showed that beta
      Lactoglobulin forms the major fraction while in case of plasma protein complex
      albumin forms the major fraction. The fractionation patterns of different
      complexes with HEC, CMC or TCA gave the same components and about the same ratio.
      It appears from these results that HEC-protein complexes are preferable than CMC
      protein complexes or proteins precipitated by TCA. Chemical analysis of whey
      protein complexes revealed that lactose content of whey protein-HEC-complex was
      higher than that of CMC-complex or protein precipitated by TCA. Elemental
      analysis of protein complexes showed that the level of sodium, phosphorus, and
      potassium was increased while that of copper or zinc decreased. Cellulose
      derivative protein complexes showed no significant effects on the liver or kidney
      function of albino rat and these results indicted that no toxic effect was
      observed from the uses of these protein complexes in feeding.

PMID- 9584276
TI  - Determination of zinc, cadmium, lead and copper in wines by potentiometric
      stripping analysis.
AB  - A method for determination of zinc, cadmium, lead and copper in wines by means of
      potentiometric stripping analysis (PSA) is described. Cadmium, lead and copper
      are determined directly, whereas the zinc determination is possible only after
      the wine samples decomposition. The results for five red and white Yugoslav wines
      are given. The content of zinc, cadmium, lead and copper in analyzed samples were
      in the range of 0.16-0.79, 0.010-0.045, 0.13-0.27 and 0.10-0.46 mg/l,
      respectively. The contents of the all analyzed metals were below the maximum
      ordered by the Yugoslav law.

PMID- 9584277
TI  - Occurrence of pesticides in fish tissues, water and soil sediment from Manzala
      Lake and River Nile.
AB  - Pesticides constitute the major source of potential environmental hazard to man
      and animal as they are present and concentrated in the food chain. This study was
      conducted on 136 samples of water, sediment and fish for detection and
      determination of pesticide residues in this ecosystem. Highly significant
      differences were found in levels of Indian, heptachlor, endrin, dieldrin, P,P'
      DDE and propoxur in River Nile water when compared with that of Manzala Lake.
      Levels of Indian, endrin, malathion and diazinon were significantly higher in
      soil sediment of Manzala Lake, while the levels of heptachlor, aldrine, P,P'-DDE,
      DDT, parathion, propoxur and zectran were significantly higher in soil sediment
      of River Nile. Boury fish of Manzala Lake contained higher levels of heptachlor,
      aldrin, P,P'-DDE and malathion, while boury fish of River Nile contained a higher
      level of zectran only. This survey, thus indicated that Manzala Lake and even the
      River Nile which was used as control are heavily contaminated with chlorinated
      hydrocarbons (Indian, heptachlor, aldrin, endrin, dieldrin, P,P'-DDE and DDT),
      organic phosphorus compounds (malathion, dimethoat, diazinon and parathion) and
      carbamate pesticides (propoxur and zectran).

PMID- 9584278
TI  - Relationship between environmental pollution in Manzala Lake and health profile
      of fishermen.
AB  - Manzala Lake exposed to many pollutants including untreated sewage, agricultural
      and industrial wastes which increase the concentration of heavy metals, and
      compromise the health state of the fishermen. This study investigated 100
      fishermen and 100 males of other occupations as controls. Both groups work in and
      live on and around the lake. Clinical examination revealed no significant changes
      between the fishermen and control group as regards the cardiovascular,
      gastrointestinal and dermatological systems. However, the urinary,
      musculoskeletal and respiratory symptoms were significantly higher in fishermen
      than in control males. There was a significant decrease in neutrophils (48.8%)
      and a significant increase in lymphocytes and eosinophils (35.4% and 9%),
      respectively. Hepatotoxicity was evidenced by an increase in serum aspartate
      transaminase and alanine transaminase. There were no significant differences in
      serum creatinine and urea between fishermen and control. Levels of lead, cadmium
      and mercury in water and sediment were 0.26, 0.014, 0.002 mg/l, and 33.5, 1.37,
      0.28 micrograms/kg, respectively. Levels of the three heavy metals in the fish
      samples and serum of fishermen and control males in average were 1.06, 0.18,
      0.00025 ppm, 523, 33.5, 13.7 micrograms/l and 374, 12.8 11.2 micrograms/l,
      respectively. This study aimed to establish the relation between the
      environmental pollution and the health status of the population inhabiting the
      contaminated areas.

PMID- 9584279
TI  - Intracerebral hematomas caused by aneurysm rupture. Experience with 67 cases.
AB  - During a six-year (1986-1992) 334 patients with subarachnoid hemorrhage (SAH)
      were admitted to the Department of Neurosurgery. Medical University of Lubeck,
      Germany. In 281 patients the SAH was caused by rupture of an intracranial
      arterial aneurysm, verified by angiography, postmortem examination, or at
      emergency operation without angiography. In 67 (23.8%) of the 281 aneurysmal SAH
      patients the initial computerized tomography (CT) demonstrated an intracerebral
      hematoma (ICH). An ICH localized in the temporal lobe due to the rupture of a
      middle cerebral artery (MCA) aneurysm was found in 47 patients (70.2%). Forty
      three patients were considered for surgery with a surgical mortality of 8
      (18.6%). In the group of 19 ICH patients not operated upon, 16 individuals died
      (84.2%). We therefore advocate active surgical management of ICH patients:
      hematoma evacuation and aneurysm clipping at the same operation. Emergency
      surgery in younger patients (grade V) with temporal ICH suggesting the rupture of
      a MCA or internal carotid artery (ICA) aneurysm can be done without angiography.

PMID- 9584280
TI  - Clinical significance of acute traumatic intracranial pneumocephalus.
AB  - Among 1142 patients with head injuries hospitalized in the Neurosurgery
      Department of Gazi University Medical School during the period between 1979 and
      1992, 583 had initial CT scans. A retrospective analysis of these initial CT
      images revealed intracranial air on admission in only 21 cases. These were
      classified as acute traumatic intracranial pneumocephalus: a potentially serious
      complication of head injury. CT scans were re-evaluated so as to reveal whether
      air was situated in the epidural, subdural, or subarachnoid spaces or
      intracerebrally; whether associated space-occupying lesions were present and
      whether the air bubbles were single or multiple. Clinical data such as the
      presence of persistent rhinorrhea and/or otorrhea, tension pneumocephalus,
      severity and type of trauma, and outcome were were also assessed to determine the
      significance of this rare finding.

PMID- 9584281
TI  - Arachnoid cysts: how do postsurgical cyst size and seizure outcome correlate?
AB  - Arachnoid cysts (ACs) are congenital cystic brain malformations associated with
      epilepsy. The purpose of this study was to determine the effect of surgical
      intervention of ACs on cyst size and seizure outcome. We reviewed the world's
      medical literature dealing with surgically treated ACs in epilepsy patients. Our
      study included only cases, in which the relationship between pre-and
      postoperative CT-size of the AC and seizure outcome was described. We also
      included six patients with ACs and epilepsy treated surgically at the University
      of Mainz. We analyzed postoperative AC size and seizure outcome with respect to
      mode of operation, cyst location, and patients' age. A total of 76 patients was
      reviewed. Sixty (79%) patients had a smaller AC postoperatively. Forty-six of
      those 60 (76.6%) experienced seizure improvement. Thirteen patients (21.6%)
      remained unchanged and one patient (1.8%) worsened. In 16 of the 76 patients
      (21%) the postoperative AC size was unchanged. Eight of those 16 patients
      improved. Six patients (37.5%) remained unchanged and two (12.5%) worsened. A
      positive correlation between postoperative AC size and seizure outcome was well
      demonstrated among patients treated by cyst fenestration, needle aspiration, or
      internal shunting. Among patients treated by cystoperitoneal shunting this direct
      correlation was less clear. Seizure outcome correlates directly with
      postoperative AC size. Seizure reduction is associated with decreased AC size
      postoperatively and depends on the mode of operation. Based on these data we
      would expect that patients with epilepsy secondary to ACs would demonstrate
      improved seizure control with lower AC volume. Conversely, we might expect
      increasing AC size to correlate with worse seizure control. This relationship may
      guide physicians in efficacy and timely patient management.

PMID- 9584282
TI  - The neurosurgical aspects of neurofibromatosis 2: diagnosis and management.
AB  - NF-2 is an extremely rare form of neurofibromatosis (NF) characterized by central
      system (CNS) neural crest-derived tumors and frequently cafe au lait spots (CLS).
      The purpose of this study was to report the clinical and imaging findings of
      seven patients with this disorder and to stress that value of surgical treatment
      in its management. Seven patients between 8 and 32 years of age who had NF-2 were
      included in the study. Clinical charts, surgical and pathological findings, and
      imaging studies were reviewed retrospectively. Patients were followed up for to
      142 months. Clinical evaluation and neuroimaging studies detected the clinical
      criteria of NF-2 in all patients. Two deaths occurred after surgical intervention
      in our series. None of the patients suffered from recurrent tumor following
      surgery. Our results show that NF-2 is an uncommon entity which has a good
      prognosis after surgical intervention, in spite of the presence of multiple
      cranial and/or spinal lesions.

PMID- 9584283
TI  - High amino acid uptake in a low-grade desmoplastic infantile ganglioglioma in a
      14-year-old patient.
AB  - Amino acid uptake is higher in high-grade than in low-grade gliomas; this is the
      rationale for using radioactively labelled amino acids for the non-invasive
      grading of brain neoplasms. We present a 14-year-old boy with a low-grade
      desmoplastic infantile ganglioglioma (DIG) that exhibited marked contrast
      enhancement on magnetic resonance imaging (MRI), but no signs of infiltration and
      only minimal surrounding edema. In this benign neoplasm the relative uptake of
      the radioactively labelled amino acid I-123-alpha-methyl tyrosine (IMT),
      determined using single-photon emission computed tomography (SPECT), was 3.24; it
      was considerably higher than that of eleven other pretherapeutic low-grade
      gliomas where it ranged from 1.06 to 1.94 and also markedly above that average
      value of 2.37 found in 20 high-grade gliomas. This case report illustrates that
      results from emission tomography with radioactively labelled amino acids must be
      interpreted with caution, particularly when rare tumor entities are considered in
      view of uncommon clinical or radiological findings.

PMID- 9584285
TI  - Idiopathic normal pressure hydrocephalus associated with empty sella.
AB  - A 70-year-old female presented with the clinical triad of normal pressure
      hydrocephalus (NPH) and senile tremor. Neuroimaging disclosed findings of both
      NPH and empty sella (ES). A ventriculoperitoneal shunt did not modify the
      clinical course except for a mild and transient improvement, and shunt
      malfunction occurred later on. The association of NPH and ES may result from a
      common underlying mechanism such as transient increases in intracranial pressure.

PMID- 9584284
TI  - The effects of chronic alpha-tocopherol administration on lipid peroxidation in
      an experimental model of acute spinal cord injury.
AB  - Most of the numerous experimental studies to research pathophysiological changes
      following acute spinal cord injury suggest a two-step mechanism of damage to the
      spinal cord in which the primary (direct) or mechanical injury caused by the
      trauma initiates secondary (indirect) or progressive autodestructive injury of
      the cord. During recent years, free oxygen radical generation and lipid
      peroxidation have been considered to be responsible for secondary autodestructive
      injury. Alpha tocopherol occupies an important and unique position in the overall
      antioxidant defense. Alpha tocopherol-depleted animals are generally more
      susceptible to the adverse effects of environmental agents than are supplemented
      animals. This study was planned to study the effectiveness in counteracting this
      autodestructive process by supplementing alpha-tocopherol in rats maintained on a
      nutritionally adequate diet, and also to evaluate whether it will provide
      additional protection or not. Eighty healthy Wistar rats (treatment and controls)
      were included. The treatment group received 100 mg/kg alpha tocopherol each day,
      intraperitoneally for seven days. Using a standard acute spinal cord trauma model
      in Wistar rats trauma was applied, an malondialdehyde (MDA) which is a lipid
      peroxidation product was measured in the traumatized spinal cord at various times
      following the trauma in order to indirectly evaluate the lipid peroxidation and
      generation of free oxygen radicals in a time sequence. Statistical analysis of
      the values demonstrated that malondialdehyde formation in the alpha-tocopherol
      administered group was significantly lower than in the control group. These
      findings indicate that longterm administration of alpha-tocopherol may be useful
      to decrease lipid peroxidation following acute spinal cord trauma.

PMID- 9584286
TI  - An instructive false diagnosis: steroid-induced complete remission of a CNS tumor
      -probably lymphoma.
AB  - In recent years the incidence of primary cerebral lymphomas has increased.
      Diagnosis by imaging techniques (CCT, angiography, MRT) and stereotactic biopsy
      are considered as reliable diagnostic tools. Therapeutically a combination of
      radio-, steroid- and chemotherapy is recommended. We report a case of space
      occupying CNS lesion in which the radiopaque enhancing process completely
      disappeared after biopsy and steroid therapy. A year later the tumor recurred on
      the other side and again regressed after steroid therapy. The first biopsy showed
      signs of a papillar tumor, so a choroid plexus papilloma was suspected. On
      examination of the treatment history, however, this diagnosis had to be revised.
      A primary CNS lymphoma seems most probable. The phenomenon of a tumor remission
      under steroid administration and the problems related to the differential
      diagnosis are discussed.

PMID- 9584287
TI  - Extradural hematoma of the posterior cranial fossa.
AB  - Fourteen cases of an extradural hematoma of the posterior fossa (EDHPF), are
      presented and the clinical and radiological finds are described. The onset of
      symptoms was acute in 10 patients and subacute in the other 4. Hematomas occurred
      in the younger age groups with a clear male predominance. Nine cases had suffered
      a blow to the head. A fracture of the occipital bone was seen in 86% of the
      patients. The bleeder could be identified in 10 cases, and in 6 of these the
      source was a bleeding transverse sinus. The overall mortality was 14.2%, but only
      patients with an acute course died (20%). All subacute cases survived. This study
      revealed that the most important factors influencing mortality were late
      diagnosis and late treatment. Coexisting intracranial lesions had no influence on
      mortality. According to the literature, there has been a certain decrease in
      mortality in the acute and subacute course patients since the introduction of
      computed tomography (CT) scanning. Emphasis is placed on the importance of
      occipital soft-tissue swelling and occipital fracture as clues to the possible
      presence of extradural hematomas, and of using the CT in all such patients even
      if no clinical symptoms are present.

PMID- 9584288
TI  - Nasoethmoid schwannoma with intracranial extension. Case report and review of
      literature.
AB  - Schwannomas are very rare in the nose and paranasal sinuses; their presence both
      intra-and extracranially is still rarer. Here we present a case of nasoethmoid
      schwannoma with intracranial extension into anterior cranial fossa. Clinical,
      radiological, pathological and operative findings are discussed and the
      literature is reviewed. We recommend bifrontal craniotomy for removal of
      intracranial and nasoethmoid extensions of this tumor.

PMID- 9584289
TI  - Intracranial metastasis of a spinal myxopapillary ependymoma. A case report.
AB  - A 37-year-old man exhibited a suprasellar tumor which histologically proved to be
      a myxopapillary ependymoma. Since these gliomas are virtually restricted to the
      cauda equina region, magnetic resonance imaging (MRI) was performed which
      revealed multiple spinal tumors. The present case seems to be the first report on
      spontaneous intracranial seeding of a spinal myxopapillary ependymoma.

PMID- 9584290
TI  - Spontaneous evacuation of cerebellar abscess through the middle ear. A case
      report.
AB  - Otogenic brain abscesses are a significant cause of mortality and morbidity in
      developing countries. Usually they occur either by distant thrombophlebitis of
      cerebral veins or by direct extension in an unsafe type of chronic suppurative
      otitis media. This case of cerebellar abscess was prepared for surgical excision,
      when sudden evacuation of pus through the left middle ear resolved the abscess
      and clinical features in the patient. No surgical intervention was required in
      this patient. The case under discussion is unique and unreported for its
      spontaneous evacuation through the middle ear.

PMID- 9584291
TI  - An unusual presentation of metastatic adenocarcinoma in the cerebellum associated
      with intratumoral hemorrhage mimicking a stroke. A case report.
AB  - Spontaneous bleeding from a metastatic tumor in the brain is usually associated
      with melanoma, choriocarcinoma, or hypernephroma. We report a patient with rectum
      adenocarcinoma which metastasized into the cerebellum and mimicked a stroke, and
      discuss the clinical features and diagnostic problems of this uncommon condition.

PMID- 9584292
TI  - The case for just plain "atrial fibrillation".

PMID- 9584293
TI  - Comparison of the effects of AV nodal ablation versus AV nodal modification in
      patients with congestive heart failure and uncontrolled atrial fibrillation.
AB  - Radiofrequency (RF) catheter ablation of the atrioventricular node (AVN) and
      implantation of a ventricular pacemaker can improve cardiac performance in
      patients with congestive heart failure (CHF) and uncontrolled atrial fibrillation
      (AF). Alternatively, RF catheter modification of the AVN has been proposed to
      slow ventricular response during AF without requirement for permanent pacing.
      Among 44 consecutive patients (mean age 69.7 +/- 10.2 years) with drug resistant
      chronic AF, 22 (group I) had AVN ablation with permanent ventricular pacemaker
      implantation, while 22 patients had attempted AVN modification. Complete AV block
      was obtained in all group I patients while only seven (32%) AVN modification
      patients (group II) had permanent slowing of ventricular rate. Among patients in
      group I, mean left ventricular ejection fraction (EF) increased from 32.2% +/-
      8.8% before ablation to 41.9% +/- 14.6% 4-weeks postablation (P < 0.01); exercise
      tolerance time (ETT) increased from 2.9 +/- 2.2 minutes to 4.5 +/- 2.9 minutes (P
      < 0.01); and quality-of-life score decreased from 66.1 +/- 22.6 to 36.9 +/- 17.1
      (P < 0.01). By comparison, there was only a small increase in ETT in the seven
      successful group II patients (2.4 +/- 1.8 minutes to 3.0 +/- 1.9 minutes; P <
      0.05) and there was no significant change in EF or quality-of-life. While AVN
      ablation can occasionally have transient adverse effects, it is more effective
      than AVN modification for improving cardiac performance in selected patients with
      CHF and AF.

PMID- 9584294
TI  - Cerebral syncope: loss of consciousness associated with cerebral vasoconstriction
      in the absence of systemic hypotension.
AB  - Transcranial Doppler (TCD) ultrasonography done during head-upright tilt induced
      neurocardiogenic syncope has demonstrated that cerebral vasoconstriction occurs
      concomitant with (or precedes) loss of consciousness. This article demonstrates
      evidence that cerebral blood flow changes alone (vasoconstriction), in the
      absence of systemic hypotension, may result in syncope. Five patients (4 men, 1
      woman; mean age 41 +/- 17 years) with recurrent unexplained syncope were
      evaluated by use of an upright tilt table test for 45 minutes with or without an
      infusion of low dose isoproterenol. TCDoppler ultrasonography was used to assess
      middle cerebral artery systolic velocity (Vs); diastolic velocity (Vd); mean
      velocity (Vm); and pulsatility index (PI = Vs = Vd/Vmean). Syncope occurred in
      five patients during the baseline tilt and in one patient during isoproterenol
      infusion. During tilt induced syncope, at an average mean arterial pressure of 89
      +/- 16 mmHg, TCD sonography showed a 2% +/- 10% increase in systolic velocity; a
      51% +/- 27% decrease in diastolic velocity; and a 131% +/- 87% increase in
      pulsatility index. One patient underwent continuous electroencephalographic
      recording during tilt, which demonstrated diffuse slow wave activity (indicating
      cerebral hypoxia) at the time of syncope concomitant with the aforementioned TCD
      changes in the absence of systemic hypotension. These findings reflect an
      increase in cerebrovascular resistance secondary to arteriolar vasoconstriction
      distal to the insonation point of the middle cerebral artery, that occurred
      concomitant with loss of consciousness and in the absence of systemic
      hypotension. We conclude that in some individuals abnormal baroreceptor responses
      triggered during orthostatic stress may result in a derangement of cerebral
      autoregulation leading to cerebral vasoconstriction with resultant cerebral
      hypoxia in the absence of systemic hypotension.

PMID- 9584296
TI  - Repetitive ventricular responses induced by radiofrequency ablation for
      idiopathic ventricular tachycardia originating from the outflow tract of the
      right ventricle.
AB  - In 23 consecutive patients, radiofrequency (RF) ablation was used as treatment
      for idiopathic ventricular tachycardia (VT) originating from the outflow tract of
      the right ventricle. In this study, we focused on the repetitive ventricular
      response (> 5 consecutive QRS beats during RF application). The incidence and
      clinical implications of the repetitive ventricular response were examined
      through the results of endocardial mapping and RF ablation. VT origin was mapped
      as the earliest activation site during VT, and it was determined within 0.5 x 0.5
      cm (narrow site) in 13 patients and wider than 0.5 x 0.5 cm (wide origin) in the
      other 10 patients. The repetitive ventricular response was induced during
      application of RF current in 14 of 23 patients (61%), and it was more frequently
      observed in VT from a wide origin (100%) than in the VT from a narrow site (31%).
      The QRS morphology of the repetitive ventricular response was identical to that
      of clinical VT. As RF application was continued and/or repeated, the RR interval
      of the repetitive ventricular response was gradually prolonged, the number of
      consecutive QRS complexes was decreased, and clinical VT was finally eliminated.
      The overall success rate of RF ablation was 96% (22/23 patients), and no
      complications were observed. In conclusion, a repetitive ventricular response was
      frequently observed in idiopathic right VT. The changing pattern of repetitive
      ventricular response, slowly and/or disappearing was consistent with successful
      RF ablation.

PMID- 9584295
TI  - Acute effects of radiofrequency ablation upon atrial conduction in proximity to
      the lesion site.
AB  - The electrophysiological effects of RF ablation upon the areas in proximity to
      the lesioned zones have not yet been well characterized. An experimental model is
      used to investigate atrial conduction in the boundaries of RF damaged zones. In
      11 isolated and perfused rabbit hearts, endocardial atrial electrograms were
      recorded using an 80-lead multiple electrode positioned in the left atrium. Both
      before and after the RF application (5 W, 8 s, 1-mm diameter unipolar epicardial
      electrode) in the mid-portion of the free left atrial wall, measurements were
      made of conduction time from the pacing zone (posterior wall of the left atrium)
      to three points between 7.5 and 7.9 mm distal to the damaged zone. Conduction
      velocity and the direction of the activation propagation vector were determined
      in ten groups of four electrodes positioned around the damaged zone, and at the
      left atrial appendage. The mean diameter (+/- SEM) of the transmural lesions
      produced by RF ablation and defined by macroscopic examination was 4.2 +/- 0.2
      mm. The conduction times to the three points distal to the lesion site were
      significantly prolonged as a result of RF ablation; 7.6 +/- 0.4, 7.4 +/- 0.5, and
      6.9 +/- 1.0 ms (control); and 11.3 +/- 1.0 (P < or = 0.01), 11.1 +/- 1.3 (P <
      0.01), 10.6 +/- 1.4 ms (P < 0.05) (post-RF). The differences between the
      conduction velocities determined in the areas surrounding the lesion, before and
      after RF application, failed to reach statistical significance: 86.2 +/- 6.5 cm/s
      (control) versus 75.5 +/- 5.7 cm/s (post-RF) (NS). After RF, significant
      variations were only observed in the direction of impulse propagation in the
      proximal-inferior quadrant adjacent to the lesion site, the difference being -61
      degrees +/- 18 degrees (P < 0.02). In 2 of 4 experiments in which the lesion size
      was increased by a second RF application (5 W, 16 s), tachycardias with
      activation sequence around the lesion could be induced, with cycle lengths of 56
      and 50 ms, respectively. In the atrial wall, the conduction times to the regions
      distal to the RF lesion are significantly prolonged. No significant changes are
      observed in conduction velocity in the areas in proximity to the lesion.
      Prolonged conduction to the areas distal to the ablation site is due to the
      lengthened pathway traveled by the impulses in reaching these areas. Tachycardias
      with activation patterns that suggest reentry around the RF damaged zone may be
      induced.

PMID- 9584297
TI  - The effect of maximum heart rate on oxygen kinetics and exercise performance at
      low and high workloads.
AB  - The normal heart rate is linearly related to oxygen consumption during exercise.
      The maximum heart rate of the normal sinus node is approximated by the formula:
      HRmax = (220-age) with a variance of approximately 15%. However, the nominal
      upper rate of most permanent pacemakers is 120 beats/min, a value that remains
      unchanged for many patients. As this nominal setting falls well below the maximum
      predicted heart rate for most patients, it is possible that the chronotropic
      response of rate adaptive pacemakers during moderate and maximal exercise
      workloads may be less than optimal. The purpose of this study was to determine
      the effect of the upper programmed rate on oxygen kinetics during submaximal
      exercise workloads and maximum exercise performance during symptom-limited
      treadmill exercise. Exercise performance with an upper rate programmed to 220-age
      was compared with an upper rate of 120 beats/min. Eleven patients (5 men and 6
      women, mean age 54 +/- 10 years) with complete heart block following catheter
      ablation of the atrioventricular junction for refractory atrial fibrillation who
      were implanted with permanent, rate-modulating VVIR pacemakers comprised the
      study population. The rate adaptive sensors were based on activity in 8 patients,
      minute ventilation in 2 patients, and mixed venous oxygen saturation in 1
      patient. After performing a symptom-limited treadmill exercise test to determine
      maximum exercise capacity and to optimized programming of the rate adaptive
      sensor, each subject performed two treadmill exercise tests in random sequence
      with a rest period of at least 1 hour between tests. During one of the tests the
      upper rate was programmed to a value calculated by the formula: HRmax = (220
      age). During the other exercise test the upper rate was programmed to 120
      beats/min. Patients were blinded as to their programmed values and to the
      hypothesis of the study. A novel treadmill exercise protocol was used that
      consisted of a 6 minute, constant-workload phase at approximately 50% of maximum
      workload followed immediately by incremental, symptom-limited exercise using a
      modified Chronotropic Assessment Exercise Protocol(CAEP) with 1 minute stages
      until; peak exertion. Breath-by-breath analysis of expired gases was performed
      with subjective scoring of exertional difficulty at the end of the constant
      workload phase and during each stage of incremental exercise using the Borg
      Perceived Exertion Scale. Exercise duration was significantly longer (637 +/- 47
      vs 611 +/- 48 seconds, P < 0.005) with the higher programmed upper rate. Oxygen
      kinetics were also significantly improved with an age predicted upper rate with a
      lower O2 deficit (258 +/- 88 vs 395 +/- 155 mL, P = 0.002) and higher VO2 rate
      constant (3.6 +/- 1.0 vs 2.4 +/- 0.7, P < 0.001). The VO2max during peak exertion
      was higher with an age predicted upper rate than with an upper rate of 120
      beats/min (1807 +/- 751 vs 1716 +/- 702 mL/min, P = 0.04). The mean Borg score
      was lower during the last common treadmill stage during maximum exercise with an
      age predicted upper rate than with an upper rate of 120 beats/min (15.7 +/- 2.0
      vs 16.5 +/- 1.9, P = 0.04). The mean Borg score during submaximal, constant
      workload exercise was also lower with a higher upper rate (9.0 +/- 2.5 vs 9.6 +/-
      2.2, P = 0.10). Programming the upper rate of rate adaptive pacemakers based on
      the age of the patient improves exercise performance and exertional symptoms
      during both low and high exercise workloads as compared with a standard nominal
      value of 120 beats/min.

PMID- 9584298
TI  - Relationship between the upper limit of vulnerability determined in normal sinus
      rhythm and the defibrillation threshold in patients with implantable cardioverter
      defibrillators.
AB  - The upper limit of vulnerability is the strength above which ventricular
      fibrillation is no longer inducible with a shock delivered during the vulnerable
      phase of the cardiac cycle. It has been demonstrated that the upper limit of
      vulnerability correlates with the defibrillation threshold in a paced rhythm. The
      purpose of this study is to evaluate the correlation of the upper limit of
      vulnerability determined in normal sinus rhythm with the defibrillation threshold
      using a simplified protocol in patients undergoing placement of an ICD. We
      studied 28 patients who underwent ICD implantation. CPI generators and Endotak
      leads were used in all patients. Device-based testing was used to determined the
      defibrillation threshold and the upper limit of vulnerability. The upper limit of
      vulnerability was tested with three shocks delivered at 0, 20, and 40 ms before
      the peak of the T wave during normal sinus rhythm. The defibrillation threshold
      was determined by a simple step up-down protocol. The upper limit of
      vulnerability (9.0 +/- 4.5 J) did not significantly differ from the
      defibrillation threshold (9.9 +/- 4.0 J), P = NS. A close correlation was
      present, correlation coefficient = 0.75, P < 0.0001. The upper limit of
      vulnerability was within 5 J of the defibrillation threshold in 27 (96%) of the
      28 patients. The upper limit of vulnerability underestimated the defibrillation
      threshold by 10 J in one patient who had a defibrillation threshold of 15 J. The
      upper limit of vulnerability determined in normal sinus rhythm correlates
      significantly with the defibrillation threshold in patients undergoing ICD
      implantation. The protocol is simple and easily implemented clinically.

PMID- 9584300
TI  - Circadian variations in minute ventilation can be reproduced by a pacemaker
      sensor.
AB  - Special software allowing the memorization of 24-hour minute ventilation can be
      loaded into the memory of the Chorus RM, a DDDR pacemaker driven by minute
      ventilation. This feature was tested in the postimplant period in 13 patients.
      Measurements of minute ventilation, respiratory rate, and respiratory amplitude
      were analyzed according to prospectively defined diurnal and nocturnal time
      periods. Minute ventilation decreased by 39% (P < 0.001) from the diurnal to the
      nocturnal phase, while respiratory rate and amplitude decreased by 18% and 28%,
      respectively (P < 0.001 each). Thus, minute ventilation allowed discrimination
      between sleep and waking hours. This information could be utilized to modulate
      the backup rate of the pacemaker.

PMID- 9584299
TI  - Is the atrial high rate episode diagnostic feature reliable in detecting
      paroxysmal episodes of atrial tachyarrhythmias?
AB  - The atrial high rate episode diagnostic in the Thera pacemaker reports frequency,
      duration, and date/time of atrial tachyarrhythmias according to programmed
      criteria. The aim of the study was to validate the atrial high rate episode
      diagnostic feature. Episodes of atrial fibrillation recorded by Holter monitoring
      were compared to episodes detected by the pacemaker. Forty five ambulatory
      (Holter) recordings were used for evaluation. Thirty of 45 ambulatory (Holter)
      recordings showed sinus rhythm. On 4 of these 30 ambulatory (Holter) recordings,
      the Thera detected 12 episodes of atrial tachyarrhythmias as false-positives
      (sinus rhythm was detected as atrial tachyarrhythmia). The main reason was far
      field R and T was oversensing. On 15 of 45 ambulatory (Holter) recordings, 125
      episodes of atrial tachyarrhythmias were recorded. Ninety-three of these events
      also were detected by the pacemaker, while for 32 events the Thera reported sinus
      rhythm. The main reason was that the episodes were of too short duration.
      Therefore, the Thera (programmed with detection rate 160 beats/min, detection
      beats 40, termination beats 10) was unable to detect atrial tachycardias.
      Software simulation of the diagnostic algorithm under several programming
      settings using the digitized Holter files demonstrated highly reliable detection
      of atrial tachyarrhythmias (sensitivity 98%, specificity 100%) when programmed as
      follows: detection rate 220 beats/min, detection beats 10, termination beats 20.
      It can be concluded that Thera's high rate episode monitor is a reliable tool for
      detection of atrial tachyarrhythmias, if programmed as recommended.

PMID- 9584301
TI  - Short-term atrioventricular sequential pacing does not adversely affect
      collateral blood flow: a study during angioplasty.
AB  - Altered sequence of ventricular activation sequence results in marked
      derangements in mechanical events. In the present study, we investigated the
      comparative effects of atrial and AV sequential pacing on collateral blood flow
      during angioplasty. Twenty-eight patients with stable angina and left anterior
      descending artery disease undergoing balloon angioplasty were studied. Collateral
      flow was determined during balloon inflation from the distal flow velocity of the
      ipsilateral artery (17 patients) or from the increase of the maximal diastolic
      blood flow velocity (Vc) of the contralateral artery (11 patients). Flow
      measurements were made using the Doppler flow guidewire. The relative resistance
      in the collateral vascular bed (RR) also was estimated in the latter group of
      patients. After the first balloon inflation, two similar consecutive balloon
      inflations were done under atrial and AV sequential pacing, at a rate of 15
      beats/min higher than the sinus rate, in the absence of vasoactive medication.
      One minute after the initiation of pacing, the second and third balloon
      inflations were begun and the pacing continued until the balloon inflations were
      completed. In the ipsilateral group, average peak velocity was 84.6 +/- 24.2 mm/2
      during atrial pacing and 82.7 +/- 29.7 mm/s during AV sequential pacing (P = NS).
      In the contralateral group, Vc was 18% +/- 12% during atrial pacing and 17% +/-
      14% during AV sequential pacing, and the RR was 4.5 +/- 4.7 and 4.9 +/- 6.4,
      respectively (both P = NS). The coronary wedge/mean blood pressure was similar
      during the two tested balloon inflations. Short-term AV sequential pacing at rest
      does not adversely affect collateral blood flow and resistance in patients with
      left anterior descending artery disease.

PMID- 9584302
TI  - Microwave catheter ablation using a clinical prototype system with a lateral
      firing antenna design.
AB  - Microwave has been considered a potentially more effective and more versatile
      form of energy than radiofrequency. Its feasibility has been tested using various
      prototype systems and catheter designs. This study assessed the safety and
      efficacy of a clinically-suitable prototype microwave power supply and catheter
      system with a lateral-firing antenna design for atrioventricular (AV) junction
      ablation in canines and to correlate with tissue histopathology. The system
      consisted of a deflectable catheter with a 6-mm antenna and a thermocouple; and a
      2.45-GHz frequency generator with power, time, and temperature controls. AV
      junction ablations were performed using 75 W energy for up to 60 seconds.
      Effective heating was confirmed by a rise in catheter temperature to 69.3 +/- 8.8
      degrees C. Complete AV nodal block was accomplished in all canines after an
      average of 4.1 +/- 2.8 applications at 66.8 +/- 7.7 degrees C, and persisted
      after 28 days in all chronic animals. Lesions were consistent with thermal
      necrosis, were hemispherical to semi linear in shape and have distinct borders.
      Acute lesions were 3.4 +/- 1.5 mm wide, 4.8 +/- 2.1 long, and 2.0 +/- 0.9 deep.
      Chronic lesions showed typical healing and were smaller in size. Ablations did
      not cause any transvalvular, vascular or other cardiac structural damage, and no
      coagulum formation was noted on the antenna or catheter tip. Microwave AV
      junction ablation using this clinical prototype system specifically designed for
      it was safe and effective. Lesion's depth was limited to 5 mm with 60-second
      heating while its shape corresponded to the antenna's length. Microwave energy
      may provide greater versatility for producing discrete or linear ablation.

PMID- 9584303
TI  - Failure of third-generation implantable cardioverter defibrillators to abort
      shock therapy for nonsustained ventricular tachycardia due to shortcomings of the
      VF confirmation algorithm.
AB  - Unnecessary shocks by ICDs for rhythms other than sustained VT or VF have been
      described as the most frequent adverse event in ICD patients. To avoid
      unnecessary shocks for self-terminating arrhythmias, the third-generation Jewel
      PCD defibrillators 7202, 7219, and 7220 Plus use a specially designed VF
      confirmation algorithm after charge end. The purpose of this study was to
      determine the ability of this VF confirmation algorithm to recognize nonsustained
      VT, and to analyze the reasons for failure of the PCD device to abort shock
      therapy for nonsustained VT despite use of this VF confirmation algorithm.
      Analysis of stored electrograms of electrical events triggering high voltage
      capacitor charging in the programmed VF zone of the device showed 36 spontaneous
      episodes of nonsustained VT (227 +/- 21 beats/min) during 18 +/- 7 months follow
      up in 15 patients who had a Jewel PCD implanted at our hospital. Intracardiac
      electrogram recordings and simultaneously retrieved marker channels demonstrated
      that the ICD shock was appropriately aborted according to the VF confirmation
      algorithm in 24 (67%) of 36 episodes of nonsustained VT. Twelve episodes (33%) of
      nonsustained VT, however, were followed by spontaneous ICD shock in 6 (40%) of
      the 15 study patients. The only reason for all 12 shocks for sustained VT was the
      inability of the device to recognize the absence of VT after charge end due to
      shortcomings of the VF confirmation algorithm: 11 of the 12 shocks for
      nonsustained VT were triggered by the occurrence of paced beats during the VF
      confirmation period and 1 shock for nonsustained VT was triggered by the
      occurrence of 2 premature beats after charge end. Thus, better VF confirmation
      algorithms need to be incorporated in future PCD devices to avoid unnecessary
      shocks for nonsustained VT.

PMID- 9584304
TI  - Long-term effect of VVI pacing on atrial and ventricular function in patients
      with sick sinus syndrome.
AB  - We conducted a prospective, 6-month echocardiographic study on the effect of VVI
      pacing on left atrial and ventricular function and dimensions in patients with
      sick sinus syndrome. Thirty-nine patients (23 women and 16 men, aged 71 +/- 9.2
      years; 30 in sinus rhythm and 9 in atrial fibrillation) who had a VVI pacemaker
      implanted because of sick sinus syndrome were recruited in the study. In 26
      patients who presented with and remained in sinus rhythm, paced left ventricular
      ejection fraction and stroke volume were significantly decreased (71.4% +/- 11.8%
      to 67.0% +/- 13.6%, and 73.9 +/- 29.0 cm3 to 66.3 +/- 21.1 cm3, respectively, P <
      0.001 for both), whereas the paced diastolic dimension of the left atrium was
      significantly increased (3.2 +/- 0.7 cm to 3.7 +/- 0.9 cm, P < 0.001) at 6 months
      as compared with preimplantation. In nine patients with atrial fibrillation at
      implantation paced left ventricular ejection fraction at follow-up was
      significantly decreased (67.7% +/- 10.1% to 64.2% +/- 10.6%, P =0.003), but paced
      stroke volume and left atrial diastolic dimension were not significantly changed
      (75.1 +/- 25.6 cm3 to 79.0 +/- 22.7 cm3, and 4.3 +/- 1.2 cm to 4.6 +/- 1.5 cm, P
      = NS for both) at follow-up. Cessation of pacing and restoration of sinus rhythm
      in 21 patients at follow-up did not result in any significant change of ejection
      fraction (67.5% +/- 10.2% ti 67.6% +/- 9.7%, P = NS) whereas stroke volume was
      increased (59.1 +/- 19.6 cm3 to 69.1 +/- 22.3 cm3, P < 0.0001) in comparison with
      paced values. However, compared with preimplantation values, ejection fraction
      was significantly decreased (70.4% +/- 10.0% to 67.6% +/- 9.7%, P = 0.001),
      whereas stroke volume was not significantly changed (68.4 +/- 22.3 cm3 to 69.1 +/
      22.3 cm3, P = NS) during sinus rhythm at follow-up. In 14 of those patients,
      discontinuation of pacing resulted in a significant increase of left atrial
      fractional shortening (8.1% +/- 1.7% to 20.1% +/- 4.3%, P < 0.001) and
      significant increase of left atrial diastolic dimension compared with paced and
      preimplantation levels (3.8 +/- 0.7 cm vs 3.6 +/- 0.7 cm and 3.0 +/- 0.5 cm,
      respectively, P < 0.001). Long-term VVI pacing in patients with sick sinus
      syndrome results in increase of the left ventricular end-systolic dimension and
      permanent reduction of the left ventricular ejection fraction. In the left
      atrium, VVI pacing causes an immediate reduction of the fractional shortening as
      well as long-term increase of the diastolic dimension.

PMID- 9584305
TI  - Radiofrequency ablation of anteroseptal, para-Hisian, and mid-septal accessory
      pathways using a simplified femoral approach.
AB  - Feasibility of RF ablation using a simplified two-catheter technique from a
      femoral approach was studied in 97 consecutive patients with a manifest or
      concealed accessory pathway located at the anteroseptal, mid-septal, and para
      Hisian areas. RF was applied at the site with the shortest V-delta interval or
      the earliest retrograde atrial activation during orthodromic tachycardia or right
      ventricular pacing. Ablation was initially successful in 88 of 97 patients (91%).
      Success rate was 94% (16/17) for anteroseptal, 94% (39/43) for para-Hisian, and
      89% (33/37) for mid-septal accessory pathways, without differences between
      manifest and concealed pathways for any of the locations. Mean number of RF
      pulses was 8 +/- 5 for anteroseptal, 6 +/- 6 for mid-septal, and 12 +/- 13 for
      para-Hisian accessory pathways. Two patients (2%) required implantation of a
      permanent pacemaker for complete AV block. At a mean follow-up of 27 +/- 14
      months, four patients with previous manifest preexcitation experienced resumption
      of intermittent preexcitation, but only one required a second successful
      procedure for recurrence of palpitations. RF ablation can be used effectively and
      without impairment of normal AV conduction in the majority of patients with
      anteroseptal, para-Hisian, and mid-septal accessory pathways using a simplified
      two-catheter technique from a femoral approach.

PMID- 9584306
TI  - Rhythm management in atrial fibrillation--with a primary emphasis on
      pharmacological therapy: Part 2.
AB  - Atrial fibrillation (AF) is the most common, sustained, symptomatic
      tachyarrhythmia that clinicians are called upon to manage. Management strategies
      include ventricular rate control coupled with anticoagulation, versus restoration
      and maintenance of sinus rhythm. Rate control may be achieved pharmacologically,
      with agents that impair AV nodal conduction directly and/or by increasing
      parasympathetic/sympathetic balance, or by modifying or ablating the AV nodal
      region anatomically. Rhythm control may be achieved by electrical or
      pharmacological conversion followed by maintenance of sinus rhythm by
      pharmacological (or occasionally ablative) therapies. This article will present
      current approaches to rate and rhythm control issues in AF. Part 1, published
      previously, dealt with rate control. Part 2, the current article, details
      approaches to the restoration of sinus rhythm by electrical and pharmacological
      means. The former may use transthoracic or catheter-based energy delivery
      systems. The latter may use intravenous or oral drug approaches. Part 3, to be
      published in a subsequent edition of PACE will deal with the maintenance of sinus
      rhythm.

PMID- 9584307
TI  - Funding cardiovascular research: issues and trends at the National Institutes of
      Health.

PMID- 9584308
TI  - Atrial dissociation after atrial compartment operation for chronic atrial
      fibrillation in mitral valve disease.
AB  - Atrial dissociation with segmental atrial arrhythmia is an interesting
      electrophysiological phenomenon. It was rarely reported before to be caused by
      anatomical exit block after cardiac surgery. We report the case of a 28-year-old
      patient who developed atrial disassociation after a surgical method for
      correcting atrial fibrillation--atrial compartment operation. The segmental
      atrial flutter was first found by Doppler echocardiography and proved later by
      detailed intracardiac mapping.

PMID- 9584309
TI  - Incessant fascicular tachycardia: a cause of arrhythmia induced cardiomyopathy.
AB  - An incessant ventricular tachycardia arising from the posterior fascicle is
      reported in a 29-year-old woman. This fascicular tachycardia was due to triggered
      activity and was clinically induced by an underlying paroxysmal atrial
      fibrillation. The initial echocardiographic evaluation revealed biventricular
      dysfunction with an ejection fraction of 30%. On propranolol, the patient has
      remained asymptomatic and the ventricular function has become normal after 3
      months free of arrhythmia.

PMID- 9584310
TI  - Oversensing in a cardioverter defibrillator system caused by interaction between
      two endocardial defibrillation leads in the right ventricle.
AB  - A 53-year-old male patient underwent implantable cardioverter defibrillator (ICD)
      implantation with a single lead (Endotak) transvenous system due to recurrent
      episodes of drug refractory ventricular tachycardia. After pulse generator
      replacement, inappropriate ICD shocks were observed due to muscle potential
      sensing. Intraoperatively, the old Endotak lead could not be extracted;
      therefore, it was transsected and capped. A new lead was inserted and tested
      without any problems. At the predischarge test, VF was induced and was followed
      by ICD shocks during sinus rhythm. In another surgical procedure, the old Endotak
      lead was explanted using a special instrument. The present report demonstrates
      that two endocardial Endotak leads should be avoided, because the leads may
      disturb each other and be followed by inappropriate ICD discharges.

PMID- 9584311
TI  - Carcinoma of the breast and pacemaker generators.
AB  - A 90-year-old woman developed intraductal adenocarcinoma (TNM classification pT2,
      G2) of the left breast 18 years after initial pacemaker implantation deep to the
      left breast. There was no evidence of local or distant metastasis and she was
      treated with local excision and tamoxifen.

PMID- 9584312
TI  - Catheter entrapment in the mitral valve apparatus requiring surgical removal: an
      unusual complication of radiofrequency ablation.
AB  - We describe a patient with Wolff-Parkinson-White syndrome in whom a steerable
      catheter became entrapped in the mitral valve apparatus, during radiofrequency
      ablation. Treatment consisted of surgical removed of the catheter. The occurrence
      of this previously unreported complication stresses the need for on-going
      monitoring of risk and benefits of electrophysiological interventions.

PMID- 9584313
TI  - Instantaneous lead entrapment: successful percutaneous removal using the cook
      workstation.
AB  - An unusual complication of transvenous endocardial lead placement is reported in
      which an electrode became entrapped within the vicinity of the tricuspid valve
      apparatus, resisting all initial attempts at removal. The lead was subsequently
      successfully removed percutaneously via the right femoral vein.

PMID- 9584314
TI  - Schemes of classification. Replace a number of complicated systems with a simple
      division of atrial fibrillation (AF) based on temporal pattern.

PMID- 9584315
TI  - Nomenclature and characterization of transisthmus conduction after ablation of
      typical atrial flutter.

PMID- 9584316
TI  - STIMAREC report.

PMID- 9584317
TI  - DEFIMAREC report.

PMID- 9584318
TI  - Digital 3D image reconstruction of ventriculocapillary communication as revealed
      in one case after transmyocardial laser revascularization.
AB  - TMR (Transmyocardial Laserrevascularization) was performed on the partially
      dyskinetic left ventricular anterior wall with stenotic coronary blood supply in
      a 61 year old woman with a history of angina and myocardial infarction. As an
      ischemic aneurysm developed in the anteroapical region of the TMR treated area,
      it became clear that TMR did not provide a substitute for coronary blood supply
      in this very heart region. The aneurysm was removed surgically 7 months after TMR
      and showed histopathologic features of an acute aneurysm. Three-dimensional image
      analysis helped prove the presence of linear tracks through several serial
      sections which were not easily visible in routine histology sections. Also, three
      dimensional vessel reconstruction showed a connection between a small endocardial
      pit on one serial section with the capillary network in the adjacent serial
      sections. The results should not be generalized, as currently aneurysmectomy is
      an end point not reached by the majority of TMR-treated patients.

PMID- 9584319
TI  - Immunohistochemical analysis of several proteolytic enzymes as parameters of
      cartilage degradation.
AB  - Osteoarthritis is the most common joint disease in humans. It is characterized by
      a gradual loss of extracellular matrix components of articular cartilage such as
      collagen and proteoglycan. Presently, however, emphasis is placed on enzymes
      exerting a strong influence on cartilage degradation. These enzymes include
      matrix metalloproteinases (MMP), their specific inhibitors (TIMP) and the
      plasminogen activator/inhibitor system. We applied monoclonal antibodies against
      MMP-1, -2, -3, -9 and their inhibitors TIMP-1/-2, as well as against urokinase
      plasminogen activator u-PA and its inhibitor PAI to investigate their influence
      on articular cartilage degradation in patients with varusgonarthritis. We
      examined the cartilage of the lateral and medial compartments of 20 tibia
      plateaus, which can present with slight and severe cartilage degradations at the
      same time. In doing so, we tried to show whether or not immunohistological
      detection of enzymes could serve as a parameter for chondral degradation. The
      strongest immunoreaction for all enzymes was noted in the superficial layer of
      articular cartilage both medially and laterally. Between medial and lateral
      compartments, however, there were striking differences in the immunoreaction
      intensity of chondrocytes for MMP-1 and -3 as well as for TIMP-1 and u-PA. We
      noted that in cartilage with more advanced degradation, the immunoreaction for
      these enzymes was significantly higher in medial than in lateral compartments (p
      < 0.05). At the immunohistological level, a direct correlation between the grade
      of cartilage degradation and immunoreaction intensity was found. Our results
      corroborate the assumption that the expression of certain matrix-degradating
      enzymes serves as a parameter for the grade of cartilage degradation.

PMID- 9584320
TI  - Cellular blue naevi with microalveolar pattern--a type of naevus frequently
      confused with melanoma.
AB  - We report on nine cases of cellular blue naevi with distinctive arrangement of
      cells into the microalveolar pattern. This microalveolar pattern was usually seen
      in the deeper parts of cellular blue naevi and was composed of a few epithelioid
      cells surrounded by bipolar dendritic pigmented cells. This unusual pattern often
      reminded of incipient malignant change within cellular blue naevi.

PMID- 9584321
TI  - EBV-associated primary lymphomas in salivary glands of HIV-infected patients.
AB  - The lymph nodes within and around salivary glands are commonly involved in
      inflammatory processes, but rarely the site of primary lymphomas. We observed six
      cases of primary salivary gland lymphoma in HIV-infected patients and studied
      them in parallel with three cases of primary salivary gland lymphoma unrelated to
      HIV and three cases of HIV-related salivary gland lymphadenopathies in order to
      characterize this new entity. We found that all salivary gland lymphomas in HIV
      infected patients were of high histologic grade while salivary gland lymphomas
      unrelated to HIV were predominantly of low grade MALT type. All lymphomas in both
      categories expressed the B-cell phenotype. Just as HIV-unrelated lymphomas
      frequently arise on the background of chronic inflammatory lymphoid processes,
      lesions characteristic of HIV-lymphadenopathy were still present in some
      lymphomas of HIV-infected patients. EBV RNA transcripts (EBER) were demonstrated
      in three, and latent membrane protein (LMP) in two of the six HIV-related and in
      none of the three HIV-unrelated lymphomas. The three EBER-positive lymphomas were
      of the histologic types known to express the virus in most cases. The presence of
      HIV in the form of the core protein p24 and envelope glycoprotein gp41 on the
      dendritic reticular cells of germinal centers was ascertained in the cases of HIV
      related lymphadenopathies but also in the coexistent lymphadenopathies of
      lymphomas. The practical importance of diagnosing the salivary lymphadenopathies
      and lymphomas associated with the HIV-infection resides in avoiding their
      misdiagnosis and surgical removal as tumors of salivary glands.

PMID- 9584322
TI  - Phyllodes tumour of the breast: immunohistochemical study of 37 tumours using
      MIB1 antibody.
AB  - In our study, the expression of Ki-67 antigen in phyllodes tumours of the breast
      was investigated in order to estimate its significance in assessing the grade of
      malignancy and in predicting the clinical behaviour of these tumours. Formalin
      fixed and paraffin-embedded tissue specimens of 37 cases of phyllodes tumour of
      the breast (eight graded as malignant and 29 as benign according to
      histopathological criteria) and 20 breast fibroadenomas were stained by an
      immunoperoxidase technique, using the monoclonal antibody MIB1 directed against
      cell proliferation-associated Ki-67 antigen. A MIB1 index was calculated to
      express the percentage of MIB1 positive proliferating stromal cells. Our data
      indicate that there are statistically significant differences in MIB1 indices
      between histologically benign and malignant phyllodes tumours (alpha = 0.001),
      between benign phyllodes tumour and fibroadenoma (alpha = 0.01), and between
      malignant phyllodes tumour and fibroadenoma (alpha = 0.001). Our results also
      indicate a good correlation between the conventional grading of phyllodes tumours
      based on histological criteria and MIB1 indices. However, little predictive value
      of the MIB1 index in phyllodes tumours of the breast can be derived from our
      study.

PMID- 9584323
TI  - Representativity of incisional biopsies for the assessment of flow cytometric DNA
      content in head and neck squamous cell carcinoma.
AB  - DNA flow cytometry studies of squamous cell carcinoma of the head and neck have
      shown that patients with diploid tumours have favourable prognoses, whereas the
      outcomes of those with DNA aneuploid tumours are poor. DNA flow cytometry is
      therefore increasingly used as an integral part of diagnostic procedures. To
      evaluate how representative biopsies predict the DNA ploidy of oral carcinomas,
      incisional biopsies taken pretherapeutically from 256 tumours were compared with
      the corresponding surgical resection specimens. Sixty-six tumours exclusively
      displayed cells with flow cytometrically diploid DNA content in both the biopsy
      and the subsequent resection specimen, while 182 carcinomas expressed DNA
      aneuploid tumour cell lines in matched samples. There were only 8 tumours (3.1%)
      with heterogeneity in the DNA ploidy status between the biopsy and the resection
      specimen. These results emphasise the usefulness of incisional biopsies to
      reliably prognosticate the DNA ploidy status of oral carcinomas.

PMID- 9584324
TI  - Cold acetone fixation and methacrylate embedding. A suitable method for routine
      processing of bone marrow biopsies.
AB  - Here we report that acetone fixation at -18 degrees C with subsequent embedding
      in methyl-/butylmethacrylate is a reliable method for the routine processing of
      bone marrow biopsies. This method allows good conventional histological
      visualization of morphological details, which is comparable with other fixation
      procedures. The essential advantage of this method is that a wide range of
      monoclonal antibodies and polyclonal antisera can be used for immunohistochemical
      investigations for diagnostic and scientific purposes. The addition of 5%
      polyethylene glycol 400 to the acetone minimizes freeze-related artefacts. The
      immunohistochemical demonstration of a number of antigens is mostly affected by
      the medium used for slide preparation and to a lesser extent by the concentration
      of benzoylperoxide used for polymerization. Performing polymerization at 4
      degrees C and using N, N-dimethyl-p-toluidine as accelerator allows the
      concentration of benzoylperoxide to be reduced to 0.2 g% (8.3 mmol). Under these
      conditions the methacrylate embedding procedure has only minimal effects on the
      quality of immuno- and enzyme histochemistry. Additionally, the simplified method
      for removing the polymerization inhibitor from the methacrylate components and
      the shortened impregnation step are further advantages of the embedding method
      described here.

PMID- 9584325
TI  - Benign fibromatous tumor (fibroma) of the kidney: a case report.
AB  - Benign fibromatous tumor (fibroma) of the urogenital tract is a distinctive
      pathologic entity occurring in the testis, paratesticular structures and renal
      peripelvis. We report a well-circumscribed tumor replacing the cortex and the
      medulla of more than half of the upper kidney, radiographically thought to be
      renal cell carcinoma. Histologically, the tumor was characterized by a variable
      cellularity and was composed of bland spindle-shaped cells loosely dispersed in a
      fibromyxoid to densely fibrous stroma in which calcifications and chronic
      inflammation were not observed. Immunocytochemistry showed that cells were
      positive for vimentin and, only focally, stained positive for desmin and alpha
      smooth muscle actin. Differential diagnosis included a wide spectrum of benign
      and malignant spindle cell tumors. The clinicopathologic features were consistent
      with benign fibromatous tumor (fibroma) of the kidney. To our knowledge, this is
      the first case of benign fibromatous tumor (fibroma) of the kidney reported in
      the English literature.

PMID- 9584326
TI  - Metastasizing adenocarcinoma of the female prostate (Skene's paraurethral
      glands). Histological and immunohistochemical prostate markers studies and first
      ultrastructural observation.
AB  - The case of a 46-year-old women with well-differentiated adenocarcinoma of the
      female prostate (Skene's paraurethral glands and ducts) with inguinal metastases
      is reported. Besides adenocarcinomatous structures, also more solid parts of the
      tumor and anaplastic regions with dark cells were found on histological
      examination. Clear cancerous cells were typical for glandular and solid tumor
      parts. The cancerous cells showed distinct immunohistochemical positivity of
      prostate specific antigen (PSA) and prostate (specific) acid phosphatase
      [P(S)AcP]. These are the first published results of electron microscopic
      examination of formalin fixed tissue showing the ultrastructure of female
      prostate carcinoma, comparable to that of the male prostate carcinoma. In the
      female, similar to the male, the prostate carcinoma probably originates from the
      secretory (luminal) cells of the female prostatic glands.

PMID- 9584327
TI  - Spontaneous dissecting aneurysm of coronary artery in a pregnant woman at term.
AB  - We describe a case of spontaneous dissecting aneurysm of the circumflex coronary
      artery in a 44-year-old primigravida at term with no vascular risk factors.
      Spontaneous coronary artery dissection is a very rare condition with a greater
      prevalence in women, postpartum in particular. The left anterior descending
      artery is the most frequently affected. Histologically, the most common finding
      is a hematoma occupying the outer third of the media, resulting in complete
      compression of the true lumen. Arterial wall changes during pregnancy together
      with hemodynamic factors, a lytic action of protease released from eosinophils,
      and intimal tears are the main hypotheses considered to explain the etiology of
      spontaneous coronary artery dissection.

PMID- 9584328
TI  - Cytochrome P450 specificity of metabolism and interactions of oxybutynin in human
      liver microsomes.
AB  - Oxybutynin has an extensive first pass metabolism after oral administration, the
      main active metabolite being N-desethyloxybutynin. The purpose of this study was
      to investigate the CYP isoform specificity of oxybutynin N-deethylation and
      possible interactions. Oxybutynin N-deethylation in human liver microsomes in
      vitro was potently inhibited by ketoconazole (IC50 4.5 microM), less and variably
      by itraconazole and not by quinidine or several other reference inhibitors,
      suggesting that CYP3A enzymes are predominant catalysts of the reaction.
      Recombinant CYP3A5 enzyme had higher activity in oxybutynin N-deethylation than
      recombinant CYP3A4. Ketoconazole inhibited oxybutynin N-deethylation by the
      recombinant CYP3A4 and CYP3A5 almost completely, whereas itraconazole inhibited
      the activity of CYP3A4 more potently than that of CYP3A5. Oxybutynin inhibited
      CYP3A4- and CYP2D6- associated activities (testosterone 6 beta-hydroxylase and
      dextromethorphan O- demethylase, respectively) in human liver microsomes.
      CYP1A1/2-, CYP2A6-, CYP2C9- and CYP2E1-associated activities were inhibited less
      potently or not at all by oxybutynin when compared with reference inhibitors.
      Although the reasons for the weak and variable inhibition by itraconazole remain
      to be studied, it seems that oxybutynin is predominantly metabolized by CYP3A4
      and CYP3A5 but not by CYP2D6. However, it seems to have some affinity also to the
      latter enzyme.

PMID- 9584329
TI  - Inhibitory effect of vanadium compounds on glutamate dehydrogenase activity in
      mitochondria and hepatocytes isolated from rabbit liver.
AB  - The effect of orthovanadate, vanadyl sulphate and vanadyl acetylacetonate on
      glutamate dehydrogenase activity was studied in liver mitochondria and isolated
      hepatocytes of rabbit. In permeabilized mitochondria with free access of
      substrates and drugs to glutamate dehydrogenase, orthovanadate and vanadyl
      sulphate at 200 microM concentrations decreased both glutamate synthesis and
      glutamate deamination by 80 and 50%, respectively, while vanadyl acetylacetonate
      was less potent. In view of kinetic data obtained at various ammonium
      concentrations, orthovanadate appeared to be a competitive inhibitor (Ki = 40 +/-
      3 microM), while vanadyl sulphate was a non-competitive one (Ki = 147 +/- 10
      microM). In contrast to orthovanadate, vanadyl sulphate augmented the inhibitory
      action of increased above 0.5 mM 2-oxoglutarate concentrations. All these effects
      on the enzyme activity were partially reversed in the presence of L-leucine and
      ADP, which are allosteric activators of glutamate dehydrogenase. Moreover, all
      compounds studied suppressed both glutamate formation and glutamate deamination
      in isolated hepatocytes incubated under various metabolic conditions, as
      concluded from decreased rates of glutamate and urea synthesis, respectively. In
      view of these observations it seems likely that vanadium-containing compounds may
      be potent inhibitors of glutamate metabolism in liver.

PMID- 9584330
TI  - Evidence for the activation of vitamin D compounds in the skin by side-chain
      hydroxylation.
AB  - KH 1060 is the 20-epi-22-oxa-24a-homo-26,27-dimethyl analogue of the natural
      hormone, 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). We have previously
      shown that after topical application in hairless mice both KH 1060 and 1
      alpha,25(OH)2D3 cause epidermal hyperproliferation. MC 1582 differs from KH 1060
      by the lack of hydroxyl group in the side chain which is required for receptor
      binding. We found that MC 1582 strongly stimulates epidermal hyperplasia in
      hairless mice after topical application in vivo, approaching in potency KH 1060.
      A similar, although much weaker response was also obtained with 1 alpha
      hydroxyvitamin D3 (1 alpha(OH)D3). Since only the vitamin D compounds which
      possess hydroxyl groups both in the position 1 alpha and in the side chain, bind
      to the vitamin D receptor, we suggest that a local metabolism of MC 1582 and 1
      alpha(OH)D3 takes place in the skin to the active, side-chain-hydroxylated
      species, probably to KH 1060 and 1 alpha,25(OH)2D3. This study suggests that 1
      alpha hydroxylated prodrugs may be of use in the dermatological treatment of the
      future.

PMID- 9584331
TI  - Sustained cholecystokinin-B/gastrin receptor blockade does not impair basal or
      histamine-stimulated acid secretion in chronic gastric fistula rats.
AB  - Gastrin is a physiologically important secretagogue. It is thought to stimulate
      parietal cells indirectly by mobilizing histamine from enterochromaffin-like
      (ECL) cells in the oxyntic mucosa. Gastrin stimulates the secretory activity and
      growth of the ECL cells via an action on cholecystokinin-B/gastrin receptors.
      Acute cholecystokinin-B/gastrin receptor blockade is known to inhibit gastrin
      stimulated acid secretion but whether sustained cholecystokinin-B/gastrin
      receptor blockade will impair basal, gastrin- and histamine-stimulated acid
      secretion remains uncertain. The present study was designed to study the effect
      of long-term (4 weeks) cholecystokinin-B/gastrin receptor blockade on basal and
      stimulated acid secretion in conscious rats. The selective cholecystokinin
      B/gastrin receptor antagonist YM022 (3 mumol.kg-1.hr-1) was given to gastric
      fistula rats by continuous subcutaneous infusion via osmotic minipumps for
      various times from 2 hr to 4 weeks. Basal, gastrin- and histamine-stimulated acid
      secretion were examined during and after cessation of treatment. Basal and
      histamine-stimulated acid secretion was not affected by YM022 during the 4 week
      period of administration, whereas gastrin-induced acid secretion was inhibited.
      YM022 induced hypergastrinaemia in freely fed rats but did not affect the serum
      gastrin level in fasted rats. The serum gastrin concentration and gastrin-induced
      acid secretion returned to control levels 3-7 days after termination of YM022
      administration.

PMID- 9584332
TI  - Allometric species comparison of toluene and n-hexane metabolism: prediction of
      hepatic clearance in man from experiments with rodent liver S9 in a head space
      vial equilibration system.
AB  - The liver S9 head space vial equilibration technique is an in vitro alternative
      that holds promises for a satisfactory in vivo extrapolation of liver metabolism
      of volatile organic chemicals. The aim of this study was to investigate the
      suitability of this methodology for the extrapolation of in vitro metabolic data
      from rodent to man by allometry with the two highly metabolized organic solvents
      toluene and n-hexane as model substances. The calculated hepatic clearance of
      toluene in man from rodent liver S9 in this study was equal to the reported total
      body clearance of toluene in man, suggesting insignificant extrahepatic clearance
      of toluene in humans. The calculated hepatic clearance of n-hexane was less than
      the reported values of total body clearance of n-hexane in man, indicating an
      about 80% extrahepatic clearance of n-hexane in humans. Both results are in line
      with our present knowledge of the metabolism of the two organic solvents in man.
      Allometric scaling from rodent liver S9 head space incubations to in vivo
      metabolism of toluene and n-hexane in man thus seems promising and could be a
      method of choice for scaling of organic solvent metabolism in general.

PMID- 9584333
TI  - Adenosine A1 receptor activation inhibits basal accumulation of inositol
      phosphates in rat hippocampus.
AB  - The ability of the adenosine A1 receptor selective agonist, N6
      cyclopentyladenosine, to modify basal accumulation of inositol phosphates in rat
      hippocampal slices, was investigated. Cyclopentyladenosine (10-300 nM) inhibited
      the basal accumulation of total [3H]inositol phosphates, with an EC50 of 10 nM
      and an Emax of 24%. This effect of cyclopentyladenosine was prevented by the
      adenosine A1 receptor selective antagonist, 1,3-dipropyl-8-cyclopentylxanthine
      (30 nM). Cyclopentyladenosine (100 nM) also inhibited histamine (300 nM)
      stimulated accumulation of [3H]inositol phosphates, this effect being
      quantitatively similar to that observed on basal [3H]inositol phosphates
      accumulation. The results suggest that adenosine A1 receptor activation is able,
      per se, to inhibit the formation of phosphatidylinositol-derived second
      messengers in hippocampus.

PMID- 9584335
TI  - Mitochondrial cytochrome c oxidase inhibition during acute carbon monoxide
      poisoning.
AB  - Clinical symptoms of acute carbon monoxide (CO) poisoning are mainly related to
      the capability of haemoglobin to bind CO. However, the persistence of some
      clinical alterations after carboxyhaemoglobin normalization suggests that other
      heme containing proteins, like cytochrome c oxidase, could play a role in its
      pathogenesis. We studied mitochondrial enzyme activities of lymphocytes from
      three patients suffering from acute CO poisoning. HbCO levels were 11.6%. 19.6%
      and 22.3% in the acute phase, 2.3%, 2.4% and 1.5% on day 3 after admission, and
      1.2%, 3.3% and 1.1% on day 12. Complex II, III and glycerol-3-phosphate
      dehydrogenase activities remained normal along the study, while cytochrome c
      oxidase (complex IV) activity showed a 76% inhibition compared to controls during
      acute poisoning (P < 0.01) and 48% at day 3 (P < 0.05). The activity was normal
      already on day 12 after the complete disappearance of symptomatology. Our results
      suggest that mitochondrial cytochrome c oxidase is also a target site in human
      acute CO poisoning, and its extended and generalized inhibition could explain the
      persistence of different symptoms after the normalization of HbCO levels.

PMID- 9584334
TI  - Antiproliferative activity and phototoxicity of some methyl derivatives of 5
      methoxypsoralen and 5-methoxyangelicin.
AB  - The in vitro antiproliferative activity and in vivo phototoxicity of some methyl
      derivatives of 5-methoxypsoralen and 5-methoxyangelicin, i.e. 4,4'-dimethyl-5
      methoxyangelicin (compound I), 3,4'-dimethyl-5-methoxyangelicin (compound II),
      4,4'-dimethyl-5-methoxypsoralen (compound III); and 3,4'-dimethyl-5
      methoxypsoralen (compound IV), have been investigated. The effects of the
      compounds were evaluated in vitro on HL60 and A431 cells, using 5-methoxypsoralen
      as the reference compound. In both cell lines compound I, II and III showed
      better antiproliferative activity than compound IV and 5-methoxypsoralen.
      Scanning electron microscopy revealed that all the compounds induced the
      formation of blebs and blisters on a A431 cell surface. Significant variations in
      the nuclear area strictly related to the toxicity of the compounds have been
      shown in both cell lines. Skin irritancy in vivo was evaluated by mean of
      histopathological responses on guinea-pig skin. For each compound a damage index
      was determined by morphometrical analysis of empty spaces in the epidermis.
      Histopathology revealed skin phototoxicity of compounds which lacked
      erythemogenic activity by visual scoring. By coupling cytotoxicity data in vitro
      to skin sensitization ones in vivo, compound I proved a promising candidate for
      use in clinical trials since due to a high inhibitory effect on the growth of
      human cell lines coupled to low skin phototoxicity.

PMID- 9584336
TI  - Tolbutamide: placental transfer, tissue distribution, and metabolic effects in
      murine embryos.
AB  - Tolbutamide is a sulfonylurea oral hypoglycaemic agent with suspected
      teratogenicity in humans and demonstrated teratogenicity in laboratory animals,
      but the underlying mechanism is unknown. This study examined maternal-to
      conceptus tolbutamide transfer on gestational days 9.5 and 10.5 and drug
      concentration in embryonic head, heart, and trunk regions on gestational day 10.5
      after maternal dosing in mouse. Embryos exposed to tolbutamide in vitro on
      gestational day 8.5 were assayed for glucose uptake, glycolysis, and protein
      content after 6, 12, and 24 hr. Dose-dependent tolbutamide transfer from maternal
      serum to extraembryonic fluid occurred on gestational day 9.5 and 10.5, with
      highest tolbutamide levels in embryonic heart on gestational day 10.5. In vitro
      tolbutamide exposure on gestational day 8.5 decreased glycolysis at 6 hr,
      increased glycolysis at 24 hr, and had no effect on glucose uptake at 6, 12, or
      24 hr. Embryonic protein content reflected growth retardation after 24 hr
      tolbutamide exposure. Thus, mouse embryos are directly exposed to tolbutamide
      after maternal dosing on gestational day 9.5 and 10.5, with concentration of drug
      within embryonic heart. Tolbutamide-induced changes in glucose metabolism are
      less apparent in whole embryos than reported in adult tissues.

PMID- 9584338
TI  - Pharmacological inhibition of leukotriene actions.
AB  - Leukotrienes represent a group of lipid mediators that play a very important role
      in a wide variety of pathological conditions. The presence of leukotrienes in
      inflammatory sites has been extensively documented, and accordingly research
      efforts have been directed towards the development of drugs that interfere with
      the formation or effects of leukotrienes. Although clinical application of such
      drugs has been disappointing in the past, recent discoveries of more potent and
      selective drugs seem to be promising. This review attempts to highlight some of
      these exciting developments.

PMID- 9584337
TI  - Continuous infusion of chemotherapy: focus on 5-fluorouracil and
      fluorodeoxyuridine.
AB  - Continuous infusion of chemotherapy is one of the developments to try to improve
      the treatment of metastatic cancer. There is a sound theoretical rationale to
      deliver cytotoxic drugs as a continuous infusion. Furthermore, the development of
      reliable venous access devices and portable infusion pumps enables patients to be
      treated in an ambulatory setting. This review focuses on the continuous infusion
      of the most frequently used drugs: 5-fluorouracil (5-FU) and fluorodeoxyuridine
      (FUDR). An overview is given of both preclinical studies and studies in humans.
      Continuous infusion of 5-FU and FUDR has proven to be feasible in all studies.
      However, the results (response rate and especially survival) are rather
      disappointing. So far, continuous infusion of cytostatic drugs can still be
      considered as an experimental procedure. Whether protracted, intermittent of
      circadian modulated continuous infusion is the optimal treatment schedule has
      still to be proven in future studies. Furthermore, studies are needed to
      demonstrate whether dose intensity for most tumours is important for treatment
      outcome. Also, studies are needed to investigate quality of life and economic
      issues.

PMID- 9584339
TI  - The effects of a hospital staff training program on the treatment practices of
      postoperative pain in children under 8 years.
AB  - The widespread use of day case surgery for minor operations in children places
      increased emphasis on home care, parental responsibility and attention to
      suitable analgesia. This study evaluated a training program for doctors and
      nurses on postoperative analgesia in children by following up parental
      perceptions of pain relief after discharge. The main objective of our study was
      to determine the effects of a training program on treatment practices in the
      hospital and on the home care instructions provided. The study was carried out in
      two phases. A questionnaire was sent to parents of children aged under 8 years
      who had undergone a minor otorhinolaryngological operation (tonsillectomy,
      adenoidectomy, irrigation of maxillary sinus, insertion of grommets, or
      paracentesis) at the Day Case Unit in Kuopio University Hospital. The parents of
      115 children returned the questionnaire in the preintervention study and those of
      112 children in the postintervention study (response rates: 79% and 86%
      respectively). The training program for personnel (intervention) was organized
      between the two studies. It started with a one-hour lecture on postoperative pain
      and pain treatment in children, and the lecture was followed by two weeks of
      bedside teaching. The overall standard of pain treatment in the hospital was
      good. Most of the children had no pain or only mild pain on discharge (93% before
      the intervention and 90% after the intervention). The intervention had no effect
      on the likelihood of children receiving pain medication. Noticeable changes
      occurred in the selection of pain medicines and dosage forms, and in the
      increased number of home care instructions provided for parents. We conclude that
      the training program for both professional groups (doctors and nurses) can be
      beneficial in changing the treatment practice (especially the use of medicines
      and dosage forms). Such training programs also make it possible to emphasized the
      importance of proper instructions for home care and thus to improve the quality
      of information provided for parents.

PMID- 9584340
TI  - Measurement of patient compliance.
AB  - The compliance of 91 diabetic patients using oral antidiabetics was studied.
      Patient compliance was measured using four different methods. Patients received
      their medication in a Medication Event Monitoring System (MEMS)-container. Each
      time the patient went back to the pharmacy for refill prescriptions, the number
      of tablets left in the container were counted. Pharmacy records were used to
      study the number of days of delay in getting the next refill. At the end of the
      study, a questionnaire was sent to every patient. Using MEMS as a standard, the
      results show that pill count and refill data overestimate the compliance of this
      group of patients. The MEMS data also show that the compliance data using only
      the number of tablets may be biased, because of possible overconsumption. Pill
      count does not show a correlation with compliance as measured by MEMS. The
      relation between compliance as measured with MEMS and refill compliance is weak.

PMID- 9584341
TI  - Usage patterns of benzodiazepines in a Dutch community: a 10-year follow-up.
AB  - Only a few longitudinal studies have addressed benzodiazepine use over time. We
      therefore conducted a 10-year follow-up study (1983-1992) on usage patterns of
      benzodiazepines in a Dutch community of 13 500 people. Use decreased during the
      time of the study. Twelve (1983) to ten (1992) percent of the inhabitants was a
      recipient at least once a year of a benzodiazepine prescription. The use by
      gender showed more women using more prescriptions as men. Women were not
      prescribed more DDDs per prescription as men. Individual benzodiazepines showed
      differences in use by gender. Use increased with age among both women and men.
      Most of the users were 55 years or older. One out of three patients was either an
      incidental user (1-30 days use in one calendar year), a regular (31-180 days), or
      a long term user (more than 180 days). The use of long half-life hypnotics
      decreased, the use of the short half-life ones showed an increase. Behind a
      stable overall trend we found strong fluctuations in use of individual
      benzodiazepines.

PMID- 9584342
TI  - Determination and pharmacokinetics of dextromoramide in methadone maintenance
      therapy.
AB  - To study the pharmacokinetics of dextromoramide in long-term opiate addicts on
      methadone maintenance therapy (MMT) a reverse-phase HPLC technique was developed
      to monitor dextromoramide and methadone concentrations in plasma simultaneously.
      After liquid-liquid extraction from plasma, dextromoramide and methadone were
      determined using a Supelcosil LC-ABZ column and a mobile phase of KH2 phosphate
      buffer (25 mM, pH 2.5) mixed with acetonitrile (80:20, v/v) and UV detection at
      206 nm. The method was found to be sufficiently sensitive, specific and
      reproducible to apply in six subjects on MMT for many years, receiving orally
      administered dextromoramide as adjuvant. Pharmacokinetic data sets for
      dextromoramide in each subject were conducted and analysed further, indicating
      short elimination half-life values (71 min, range 31-152 min). Contrary to
      previous studies, in all subjects tested the pharmacokinetics of dextromoramide
      are best described using an one-compartment model.

PMID- 9584343
TI  - Comparison of the effects and disposition kinetics of articaine and lidocaine in
      20 patients undergoing intravenous regional anaesthesia during day case surgery.
AB  - The aim of this investigation was to assess the effects and disposition kinetics
      of the local anaesthetic drugs (+/-) articaine and lidocaine during intravenous
      regional anaesthesia (IVRA). The mean onset time of surgical analgesia of
      articaine was 2.5 +/- 1.1 min and that of lidocaine 11.2 +/- 5.1 min (p =
      0.0006). None of the patients exhibited objective symptoms of toxicity, either
      local or systemic, during injection of articaine or lidocaine, nor were there any
      subjective complaints. No changes in blood pressure, heart rate or oxygen
      saturation were observed with these local anesthetics at any time during the
      procedure, nor after deflation of the tourniquet. After releasing the tourniquet,
      articaine appears in the blood and is rapidly eliminated with a t1/2 alpha of 5
      +/- 3 min and a t1/2 beta of 59 +/- 39 min due to hydrolysis. Lidocaine is
      rapidly and biexponentially eliminated with similar half-lives of t1/2 alpha of 4
      +/- 2 min and a t1/2 beta of 79 +/- 31 min. Total body clearance of articaine
      (8.9 +/- 3.5 L/min) is ten times greater than that of lidocaine (0.9 +/- 0.4
      L/min; p = 0.0005). We concluded that both (+/-) articaine and lidocaine are
      suitable and safe agents for IVRA with rapid onset of good surgical anaesthesia.
      Articaine is a racemic mixture, which is nowadays considered as less favourable.
      After releasing the tourniquet, articaine is eliminated with a t1/2 beta of 60
      min and lidocaine with a t1/2 beta of 80 min. Quicker onset and shorter
      elimination time favours (+/-) articaine over lidocaine for IVRA in day case
      settings so that patients treated with articaine will be 'drug free' more quickly
      than those who receive lidocaine. Faster elimination and more rapid onset are
      important advantages for articaine in IVRA for day-case procedures.

PMID- 9584344
TI  - Isotropic visual field effect on spatial orientation and egocentric localization.
AB  - The aim of this paper is to demonstrate the presence of a similar visual field
      effect on both spatial orientation and egocentric localization. A first
      experiment explored an orientation task (Visually Perceived Vertical or VPV
      determination) and compared the effects of a frame inclined either in the
      midfrontal plane (in this condition subjects assessed roll VPV) or in the median
      plane (subjects assessed pitch VPV) or in both combined planes (subjects assessed
      both roll and pitch VPV). A second experiment compared the frame effects
      specified above to the frame effect observed in an egocentric localization task
      (Visually Perceived Eye Level judgment) performed with a frame slanted in the
      median plane. The results showed that angular frame variations from -15 to +15
      deg result in the same psychometric function for both orientation and
      localization tasks. In each experiment, correlations showed that individual
      differences occur in relation to an overall sensitivity to the visual field.
      Individual sensitivity may be accounted for by a ratio of visual to graviceptive
      information which remains constant whatever the perception plane (midfrontal or
      median plane) and whatever the task (spatial orientation or localization).

PMID- 9584345
TI  - Spatial size limits in stereoscopic vision.
AB  - Stereoscopic vision is extremely precise in detecting minute differences between
      adjacent depth planes, but quite imprecise in estimating absolute depth. In this
      paper, we address the issue of the spatial acuity (and not the stereo acuity) of
      stereopsis. Static RDS (random dot stereograms) stimuli were used to find the
      spatial grain in which human stereoscopic vision operates. Using psychophysical
      experiments it was found that foveally, stimuli smaller than 8' cannot be
      accurately perceived. For other eccentricities, it was found that this threshold
      is inversely proportional to the Cortical Magnification factor. We interpret this
      spatial size limit, which is an order of magnitude larger than visual spatial
      acuity, as an indication that stereopsis is an area based comparison rather than
      a point process, and discuss the relations between the cortical 'patch' size that
      corresponds to this 8' limit and Ocular Dominance Columns.

PMID- 9584346
TI  - Spatio-temporal vernier acuity.
AB  - The study of space-time vernier (STV) provides information on the spatio-temporal
      structure of the visual system in the same way that the classical spatio-spatial
      vernier (SSV) provides information on its spatial structure. The transposition of
      a SSV task into a STV one yields the following experimental format: an object (in
      the present case a Gaussian Blob) drifts with a constant velocity, V, disappears
      at x0, t0 and reappears after a variable duration delta t at a position x1 +/-
      delta x with x1 the correct position (given a constant V) and delta x the minimum
      (positive and negative) spatial offset discriminable from x0, i.e. the STV
      threshold. Observer's task is to specify whether the reappearance position is
      ahead of, or behind x1. The STV functions of delta t measured for 1, 5 and 10
      deg/s reference velocities are linear with non-zero spatial and temporal
      intercepts at the origin. We refer to these x and t intercepts as dynamic dmin
      and tmin. Dynamic dmin is the smallest instantaneous displacement (infinite
      velocity) discriminable from a continuous drift, V. Dynamic tmin is the shortest
      'motion stop' discriminable from the same continuous drift, V. To our knowledge
      these quantities have not yet been assessed. Estimated dynamic dmin increases
      with V. whereas tmin is more or less V independent suggesting that the motion
      sensors presumably involved in the STV task have peak spatial frequencies
      inversely proportional with V and a temporal frequency characteristic independent
      of V (at least within the studied range). The observed STV linearity with the
      spatio-temporal separation implies that the STV task is equivalent to a velocity
      discrimination. Two additional observations yield support to this conclusion. (i)
      The slopes of these functions yield velocities very similar to those
      discriminable from the reference V in a standard V-discrimination experiment.
      (ii) The predicted STV performances based on a decomposition of the task into two
      velocity discrimination tasks run as independent experiments are reasonably
      accurate.

PMID- 9584347
TI  - The effect of practice on the visual detection of near-threshold lines.
AB  - Two observers practised to detect small target lines of varying luminance
      presented either within a context of collinear inducing stimuli, or without the
      context in separate blocks. A two-alternative spatial-forced-choice procedure
      using the method of constant stimuli was employed. For blocks of 500 trials,
      reflecting individual performance on five successive days of training, the
      percentage of correct responses, and the response times were analyzed. After
      several thousands of trials, i.e. several weeks of practice, both observers
      managed to detect targets presented at their strongest luminance within the
      context condition. Without the context, these targets remained undetected.
      Response times (RT) vary nonsystematically during training. Once detection is
      observed at the highest target luminance, the accuracy of the individual
      responses (percentage of correct responses) systematically increases, and
      processing speed (RT) systematically decreases with increasing target intensity.
      These results show that, within the appropriate perceptual context, practice can
      lead to a better detectability of visual stimuli presented at luminance levels
      near detection threshold. This improvement is reflected by an optimization of the
      visual integration of the different luminance levels of the target (sensory
      coding), and processing speed (response routine) during training.

PMID- 9584348
TI  - [Hepatitis in dogs; a review].
AB  - As with most liver diseases, the symptoms of hepatitis in dogs are nearly always
      aspecific: the dogs eat less, are apathetic, sometimes have polyuria/polydipsia,
      and sometimes have diarrhoea. Hepatoencephalopathy and ascites only occur with
      these symptoms in very advanced stages of chronic hepatitis. Only a part of the
      dogs have jaundice. Because of these aspecific symptoms, the diagnosis hepatitis
      is often not taken into consideration, even though the presence of a liver
      disease can be easily detected by measuring plasma concentrations of alkaline
      phosphatase and bile acids, one or both of which are elevated. The diagnosis is
      confirmed by histological examination of a liver biopsy sample. The most common
      forms of hepatitis are non-specific reactive hepatitis, acute hepatitis, and
      chronic hepatitis. Non-specific reactive hepatitis is a reaction against
      endotoxin as a result of sepsis or an increased gastrointestinal absorption.
      Treatment is directed to the primary process. Leptospirosis also causes non
      specific reactive hepatitis, but then renal insufficiency is the most prominent
      feature. The diagnosis is made not on the basis of a liver biopsy but on the
      basis of increased IgM titres against Leptospira. Immediate treatment with
      antibiotics and infusions at the first signs (jaundice and uraemia) can save the
      animal's life. Acute hepatitis can develop as a result of infection, toxins, or
      liver hypoxia. There is no specific treatment, but adequate recovery often occurs
      with supportive treatment. Corticosteroids are contraindicated. Chronic
      hepatitis, which can lead to cirrhosis, is the most common form of hepatitis. It
      is an autoimmune inflammatory reaction that is usually caused by a virus
      infection but sometimes by poisoning (intoxication). Long treatment with
      prednisolone or azathioprine is usually successful, but early recognition of the
      disease increases the likelihood of success. Nowadays, chronic hepatitis due to
      hepatic copper accumulation in Beddlington terriers can be detected by DNA tests.
      Such tests make it possible to distinguish between carriers and non-carriers.
      Affected animals can be kept symptom-free by life-long treatment with zinc
      gluconate or penicillamine.

PMID- 9584349
TI  - [Influence of a shrinking market and increasing competition on veterinary
      practice].

PMID- 9584351
TI  - Helping women select primary breast cancer treatment.
AB  - Making a decision about breast cancer treatment is complex for women. Patients
      and caregivers are given a lot of information, then asked to make choices that
      affect their lives in many ways. Many are facing their mortality for the first
      time as well. Nurses are key players in providing information and support, and
      guiding patients in making treatment choices. However, the ultimate decision is
      up to the patient.

PMID- 9584352
TI  - Breast cancer: advances in diagnosis and surgical treatment.
AB  - With breast cancer affecting more than 180,000 women per year in the United
      States, improvements in diagnosis and treatment are paramount. Nurses and members
      of the interdisciplinary care team can actively support education, treatment, and
      research in development of new techniques and therapies.

PMID- 9584353
TI  - Breast cancer options: getting through the treatment.

PMID- 9584354
TI  - Breast cancer and fatigue.

PMID- 9584355
TI  - Adjuvant therapy & breast cancer treatment.

PMID- 9584356
TI  - Treating metastatic breast cancer: principles and current practice.

PMID- 9584357
TI  - Stem cell transplantation in advanced breast cancer.

PMID- 9584358
TI  - Complementary and alternative medicine practices in women with breast cancer.

PMID- 9584359
TI  - After mastectomy: restoring cosmesis via breast reconstruction.

PMID- 9584360
TI  - From victim to Victor: taking control of breast cancer.

PMID- 9584361
TI  - Surgery of the forefoot in rheumatoid arthritis. 1960.

PMID- 9584362
TI  - Hallux metatarsophalangeal arthritis.
AB  - Arthritis of the hallux metatarsophalangeal joint is a common disorder that
      affects shoewear, ambulation, and other activities of daily living. Etiologies
      include degenerative arthritis (hallux rigidus), crystal induced arthropathy
      (gout, pseudogout), rheumatoid arthritis, the seronegative spondyloathropathies,
      posttraumatic degeneration, and advanced hallux valgus. Accurate diagnosis and
      selection of the appropriate intervention depends on recognition of pertinent
      clinical and radiographic features. This study presents a synopsis of the senior
      author's (LCS) experience with 439 surgically treated patients with hallux
      metatarsophalangeal arthritis, focusing on origin and treatment.

PMID- 9584363
TI  - Arthritis of the forefoot. A review from a rheumatologic and medical perspective.
AB  - Pain in the forefoot indicative of metatarsophalangeal synovitis often heralds
      the presence of significant inflammatory disease, and may be the initial
      presenting symptom of various systemic disorders. A review of these disorders and
      their rheumatologic, nonsurgical management is described.

PMID- 9584364
TI  - Osteoarthritis of the ankle.
AB  - Primary osteoarthritis of the ankle is a rare entity. Osteoarthritis of the ankle
      more commonly is seen secondary to trauma of the articular surface involving the
      normal biomechanics of the ankle. The causes are many and treatment consists of
      prevention of additional deterioration or treatment of that deterioration. The
      patient with osteoarthritis is plagued by chronic pain and decreased function.
      The surgical option for treatment includes soft tissue and bony debridement,
      ligamentous reconstruction, corrective osteotomy, arthrodesis, arthroplasty, or a
      combination of those treatments. The surgical treatment options are discussed and
      guidelines are provided for the treatment of ankle arthritis based on current
      concepts reported in the literature.

PMID- 9584365
TI  - Tibiotalar arthrodesis in the rheumatoid foot.
AB  - The results of 14 open ankle arthrodeses in 13 patients with rheumatoid arthritis
      are reviewed. Ten arthrodeses were treated with Charnley compression clamps (six
      of these were combined with a fibular strut graft). Three had cannulated screws
      and one had a fibular strut graft and a short leg walking cast. The mean followup
      time was 41.2 months. There were five nonunions and one delayed wound healing.
      The results of the patients treated with fibular strut grafts are far better than
      the results in patients treated with open ankle arthrodesis without grafting
      procedure. This seems a promising technique in a patient population with
      rheumatoid arthritis.

PMID- 9584366
TI  - Treatment of ankle arthrosis.
AB  - Patients with arthrosis of the ankle are seen routinely in the practice of
      orthopaedic surgery. Although the etiologies of the arthrosis may be varied, the
      treatment options are similar. These options vary with the severity of the
      symptoms, the findings on examination and radiographs, and the physical demands
      of the patients. Although there are many different conservative and surgical
      options available, it generally is accepted that arthrodesis of the ankle is the
      surgical treatment of choice for patients with significant symptoms that do not
      respond to conservative measures. Although ankle arthrodeses have been performed
      for more than 100 years, there is still little agreement as to the best method to
      achieve the best results. Various treatment options, conservative and surgical,
      available to treat patients with arthrosis of the ankle are reviewed.

PMID- 9584367
TI  - Ankle arthrodesis in patients with rheumatoid arthritis.
AB  - The results of 26 ankle arthrodeses performed for rheumatoid arthritis on 21
      patients were reviewed. Tibiotalar arthrodesis was performed in 14 ankles, and
      tibiotalocalcaneal arthrodesis was performed in 12. External fixation was used in
      20 ankles, and internal fixation was used in six. Followup was available in 24 of
      26 ankles (19 patients), and averaged 5 years (range, 2-8 years). There was no
      pain experienced in 19 ankles; mild, occasional pain was experienced in four
      ankles; and moderate, daily pain was experienced in one ankle. Daily activities
      were limited in five patients and recreational activities were limited in 11. All
      patients reported some difficulty walking on uneven terrain. Nearly all patients
      were satisfied; two were satisfied with reservations and two were dissatisfied.
      Union was achieved in 25 of 26 (96%) ankles. Ankle arthrodesis is an effective
      operation in patients with rheumatoid arthritis. Unlike previous reports, union
      and complication rates in this series were comparable with rates for arthrodesis
      for posttraumatic and degenerative arthritis.

PMID- 9584368
TI  - The role of arthroscopy in ankle and subtalar degenerative joint disease.
AB  - Treatment options for degenerative joint disease of the ankle and subtalar joints
      are limited. When conservative management fails, the only effective procedure is
      arthrodesis. With the advent of the small arthroscope and the development of
      better instrumentation and distraction techniques, small joint arthroscopy has
      gained popularity as an important diagnostic and therapeutic tool in the
      treatment of ankle and subtalar disorders. Although the benefits of arthroscopic
      ankle arthrodesis are well established, and arthroscopic subtalar arthrodesis has
      been described recently, the role of arthroscopic debridement for degenerative
      joint disease of the ankle and subtalar joints remains controversial.
      Traditionally, operative arthroscopy for ankle arthritis has not met with great
      success; however, recent studies have shown that it can provide an interim
      alternative to arthrodesis in early arthritis with preserved range of motion.
      Lesions associated with arthritis, such as impinging osteophytes and loose
      bodies, can be treated effectively with arthroscopy.

PMID- 9584369
TI  - Subtalar arthrodesis.
AB  - Subtalar arthrodesis is an accepted surgical procedure for hindfoot disorders
      including rheumatoid arthritis, postinfectious arthritis, degenerative joint
      disease, trauma, neuromuscular disorders, and residual of congenital foot
      deformities. This procedure has the advantage of joint specific stabilization
      without restricting motion in the uninvolved transtarsal joints. Several surgical
      techniques have been described with good long term results. The purpose of this
      report is to present the indications, describe a surgical technique, and discuss
      expected results of the procedure currently used. Minimal bone resection to
      achieve alignment through a small lateral incision, compression fixation, and use
      of current technology also are discussed. Modifications in technique for special
      conditions, recognition of common pitfalls, and complications are presented. The
      results in 45 patients have been encouraging and fulfill the expectations of
      surgeon and patient.

PMID- 9584370
TI  - Arthritis and arthrodesis of the hindfoot.
AB  - Arthritic involvement of the subtalar, talonavicular, and calcaneocuboid joints
      is a common cause of pain in the mature hindfoot. Inflammatory, degenerative, and
      crystalline forms of arthritis may lead to deformity and instability of joints.
      When medical and nonoperative management fails, painful joints are stabilized
      best by selective arthrodeses. Whereas, in the past, the triple arthrodesis was
      used extensively for many types of hindfoot deformities, single joint fusions now
      are used more commonly. More limited arthrodesis still may allow preservation of
      some hindfoot motion, thereby resulting in greater function. Various hindfoot
      arthritides and their biomechanical sequelae, resultant deformities, and
      treatment options are discussed. Arthrodesis continues to be the best treatment
      option for patients who have extensive hindfoot arthrosis, regardless of the
      underlying process.

PMID- 9584371
TI  - Management of heel pain in the inflammatory arthritides.
AB  - Subcalcaneal pain is a common complaint presented to the orthopaedist. Excessive
      attention to mechanical or traumatic causes may result in an improper diagnosis
      if rheumatologic or systemic conditions are not considered in the differential
      diagnosis. Systemic conditions associated with heel pain are reviewed and a
      conservative treatment protocol is presented that should help to obtain a correct
      diagnosis and to lead to effective management of this common condition.

PMID- 9584372
TI  - Prescription footwear for arthritis of the foot and ankle.
AB  - The Board Certified Pedorthist can be a valuable member of the team of healthcare
      professionals involved in the treatment of arthritis of the foot and ankle. In
      addition to providing prescription footwear, the pedorthist can assist in
      educating the patient, postoperative care, and long term monitoring of the
      patient's progress. The objectives in the pedorthic care of arthritis of the foot
      and ankle are to reduce shock and shear; to relieve excessive pressure from
      sensitive or painful areas; to accommodate, correct, and support deformities; and
      to control or limit painful motion of joints. Specific types of prescription
      footwear used to accomplish these objectives include shoes, external shoe
      modifications, and custom made foot orthoses.

PMID- 9584373
TI  - Hemochromatosis of the foot and ankle. Report of three cases and review of the
      literature.
AB  - Genetic hemochromatosis is a disorder of iron metabolism that results in
      deposition of massive amounts of iron in the tissues. Arthropathy is one of
      numerous clinical manifestations associated with this disease. Characteristic
      radiographic features have been reported in the hand and wrist, and the hip;
      however, there is no mention in the literature of joint manifestations in the
      foot and ankle. In this report, the authors present three patients with
      hemochromatosis arthropathy of the foot and ankle. Two patients presented
      primarily with foot pain and were treated initially with orthoses. One of these
      patients went on to have to midfoot arthrodesis performed. The third patient
      presented with ankle joint symptoms, and was treated successfully with an ankle
      foot orthosis. The arthritis of hemochromatosis has classic radiographic
      findings. However, the arthritis of hemochromatosis may be difficult to
      differentiate from several other joint diseases. Characteristic features of this
      disease in the foot and ankle are discussed.

PMID- 9584374
TI  - Charcot neuroarthropathy of the foot and ankle.
AB  - The goal of this study was to characterize Charcot neuroarthropathy of the foot
      and ankle by specific sites of involvement (ankle, hindfoot, midfoot, and
      forefoot), modes of presentation, methods of management, and outcome. A summary
      of treatment and results for 50 ankles, 22 hindfeet, 131 midfeet, and 18 forefeet
      is presented. Nondisplaced neuropathic ankle fractures typically healed
      uneventfully with casting and bracing. For displaced ankle fractures, closed
      reduction and casting generally resulted in loss of reduction and progressive
      deterioration; better results were obtained with open reduction and internal
      fixation, using supplemental Kirschner wires and screws. Ankles with Charcot
      neuroarthropathy and preexisting arthritis typically required arthrodesis. Of the
      ankles with neuropathic avascular talar necrosis, approximately 1/3 did well with
      nonoperative intervention and 2/3 required surgery. Chronic, unstable, malaligned
      Charcot ankles often required arthrodesis. Neuropathic calcaneal fractures were
      managed successfully nonoperatively. For feet with transverse tarsal joint
      involvement (Schon Type IV), management was more complex. Nonoperative treatment
      was successful for less than 1/2. Two thirds of the feet with midtarsus
      involvement (Schon Types I, II, and III) were managed successfully
      nonoperatively; 1/3 required surgery for recurrent ulceration, instability, or
      osteomyelitis. Half of the feet with forefoot neuroarthropathy required surgery
      for malalignment, ulceration, and/or difficulty with shoewear or braces. This
      review has established patterns of Charcot involvement of the foot and ankle with
      corresponding methods of treatment and subsequent responses. From this extensive
      clinical experience with 221 neuropathic fractures or Charcot joints,
      recommendations were derived to assist in selecting appropriate management
      options.

PMID- 9584375
TI  - Adjunct low intensity ultrasound in Charcot neuroarthropathy.
AB  - Neuropathic arthropathy or Charcot joint is a disease process that results in
      progressive destruction of bone and soft tissue secondary to the loss of
      protective sensation. The disease is most common among patients suffering from
      diabetes mellitus. Although there is no known definitive cure for the progressive
      destruction of a Charcot joint, it is possible to slow and in some cases arrest
      the destruction of the bone and soft tissue. The Charcot joint will be addressed
      with a review of the literature and use of a new technology as adjunct treatment.

PMID- 9584376
TI  - Serratus anterior dysfunction. Recognition and treatment.
AB  - Recognition of scapular winging may be difficult, and potential errors in
      treatment can result. Such treatment errors may cause morbidity for the patient.
      In addition, electrical evidence of long thoracic nerve injury usually is
      required to confirm the etiology of scapular winging as being caused by serratus
      anterior dysfunction. Although various conditions may result in scapular winging,
      primary serratus anterior dysfunction can be treated effectively by transfer of
      the pectoralis major tendon; however, this surgical approach sometimes may given
      an unacceptable cosmesis, and there may be local morbidity to the donor site of
      the iliotibial band graft that is used to augment the tendon transfer. The
      authors report eight patients with primary chronic scapulothoracic winging
      refractory to conservative treatment. Five of these patients had an incorrect
      diagnosis, and this resulted in 17 surgical procedures without resolution of
      their pain or improvement of function. Of the eight patients who required
      additional surgery to stabilize the scapula, only five patients had an
      electromyographic study that showed long thoracic nerve palsy, although all
      patients had profound scapulothoracic winging. All patients underwent a modified
      pectoralis major transfer with autogenous semitendinosus and gracilis tendon
      augmentation using two small incisions. Although one patient had a postoperative
      infection develop, the remaining seven patients had resolution of their winging,
      improved function, and satisfactory cosmesis.

PMID- 9584377
TI  - Correction of a dystrophic cervicothoracic spine deformity in Recklinghausen's
      disease.
AB  - A case is presented of a 14-year-old boy with neurofibromatosis who had a 92
      degrees dystrophic kyphosis (as measured on radiographs between C3 and C7) of the
      cervical spine. He was treated successfully by posterior stabilization and
      anterior fusion using a free vascularized fibula graft. This method appears to be
      an attractive alternative to an avascular fibula graft and avoids the risk of
      graft resorption (creeping substitution), weakening (fracture), or nonunion
      during the process of bony consolidation. It provides a stable and longstanding
      anterior strut, essential in the management of high grades of kyphosis. At 1-year
      followup the patient has no symptoms, is fully mobile, and shows radiographically
      complete incorporation of the graft with no loss of correction.

PMID- 9584378
TI  - Immediate weightbearing after uncemented total hip arthroplasty.
AB  - Radiographic subsidence of the femoral prosthesis and clinical results after
      unilateral and simultaneous bilateral uncemented total hip arthroplasty were
      compared. Patients who had bilateral total hip arthroplasty began weight-bearing
      as tolerated on both lower extremities the day after surgery. Patients who had
      undergone unilateral total hip arthroplasty were maintained at 10% weightbearing
      on the operative limb for 6 weeks after surgery. Patients in both groups were
      matched for age, gender, and weight. Minimal followup was 2 years. There was no
      difference between the two groups in terms of clinical results. Radiographic
      assessments were performed immediately after surgery, 6 weeks after surgery, and
      again at 2 years after surgery. Radiographs were reviewed by a single observer
      and analyzed with a digitized data recorder. Increased subsidence of the femoral
      prosthesis within the bilateral group was found at 6 weeks. The mean subsidence
      of the femoral prosthesis at 6 weeks for the bilateral total hip arthroplasty
      group was 0.86 mm (range, 0.18-2.60 mm) and for the unilateral group was 0.39 mm
      (range, 0.07-1.46 mm). However, subsidence occurring between 6 weeks and 2 years
      averaged 0.50 mm (range, 0.09-1.10 mm) for the bilateral group and 0.54 mm
      (range, 0.03-0.99 mm) for the unilateral group. This difference was not
      significant. At the 2-year followup, all femoral prostheses in both groups
      appeared radiographically stable with evidence of bone ingrowth and no
      indications of loosening. Thus, immediate weightbearing after bilateral total hip
      arthroplasty in this study resulted in more initial subsidence (during the first
      6 weeks after surgery) of the femoral prosthesis but did not preclude the
      prosthesis from becoming stable and achieving bone ingrowth. Patients in both
      groups obtained satisfactory clinical results. Because initial stability and bone
      ingrowth are factors influenced by prosthesis design, the results of this study
      may not be applicable to all implants.

PMID- 9584379
TI  - Proximal and distal femoral centralizers in modern cemented hip arthroplasty.
AB  - Third generation cementing techniques using intramedullary restrictors, low
      porosity cement with pressurization, lavage, and cement-stem bond enhancement do
      not prevent implant malalignment and inadequate cement mantle thickness. This has
      led to the development of modular proximal and distal centralizers to control the
      alignment of the femoral component and maintain an adequate thickness of the
      cement, thereby theoretically decreasing the rate of aseptic loosening. A
      retrospective analysis was performed of 100 primary cemented centralized femoral
      components. At an average followup of 5.7 years (range, 4-8 years), the average
      Harris Hip Score was 90. There were no cases of aseptic loosening, osteolysis, or
      impending failure. Ninety-one percent of femoral stems were implanted with
      satisfactory alignment with an optimal cement thickness. However, six distal
      centralizers and one proximal centralizer fractured at the time of insertion and
      voids frequently were seen in and around the distal centralizer. Although
      centralizers improve prosthesis alignment and cement mantle thickness, the long
      term effects of centralizer fracture and distal cement voids need to be observed
      to determine if centralizers improve previous implant survival.

PMID- 9584380
TI  - Medial soft tissue restraints in lateral patellar instability and repair.
AB  - This study was undertaken to evaluate the medial ligamentous stabilizers of the
      patella in restraining lateral displacement and to assess their relative
      contribution after individual repair. Seventeen fresh frozen human anatomic
      specimen knee joints were studied. The specimens were loaded onto a testing
      instrument that was designed to measure the compliance of the medial and lateral
      patellar restraints in the coronal plane. Two different cutting and repair
      sequences were used to test the individual contributions of the patellar
      ligaments. The medial patellofemoral ligament was found to be the major medial
      ligamentous stabilizer of the patella. Isolated release resulted in a 50%
      increase in lateral displacement, and isolated repair restored balance to the
      patella. In addition, the patellotibial and patellomeniscal ligament complex
      played an important secondary role in restraining lateral patellar displacement.
      Isolated repair of these ligaments restored balance to near normal levels. The
      medial patellofemoral retinaculum played only a minor role in patellofemoral
      instability. Proximal realignment or medial ligament repair for patellofemoral
      instability specifically should address repair of the deep layers that contain
      the restraints to lateral patellar displacement. Failure to include these
      structures in repair, especially of the medial patellofemoral ligament, may lead
      to persistent or recurrent instability.

PMID- 9584381
TI  - Femoral condyle geometry in the normal and varus knee.
AB  - Femoral condyle geometry was evaluated in 30 normal and 30 varus knees using
      magnetic resonance imaging. In the sagittal view, the distal part of the medial
      condyle was deformed in the varus knees, but there was no significant difference
      in the posterior part of the medial condyle between the normal and varus knees.
      In the transverse view, the transepicondylar axis (a reliable rotational
      landmark) showed approximately 6 degrees external rotation relative to the
      posterior condylar axis in the varus knees and the normal knees. The results of
      this study suggest that no hypoplasia exists at the posterior part of the medial
      condyle in varus knees. In addition, the posterior condylar axis may be a
      reliable rotational landmark but is in relative internal rotation in varus knees
      when total knee arthroplasty is performed.

PMID- 9584382
TI  - Significance of abnormalities of chromosomes 5 and 8 in chondroblastoma.
AB  - Tumor specific chromosomal abnormalities have been identified in several
      histologic subtypes of benign and malignant bone tumors. These anomalies have
      proven to be useful diagnostically. Characterization of recurrent chromosomal
      abnormalities also has provided direction for molecular investigations of
      pathogenetically important genes. Cytogenetic reports of chondroblastoma, a rare
      benign bone tumor, are few. Cytogenetic analysis of a benign and a malignant
      chondroblastoma in this study revealed the following abnormal chromosomal
      complements: 47,XY,+5,t(5;5)(p10;q10) and 45,
      XY,del(2)(p23),del(3)(q23q27),dup(8)(q12q21.), del(11) (q14q23), -13, add (17)
      (q25) x 2, respectively. Although a specific chromosomal abnormality has not yet
      emerged for chondroblastoma, abnormalities of chromosomes 5 and 8 have been
      reported previously in this neoplasm, suggesting preferential involvement of
      these two chromosomes.

PMID- 9584383
TI  - Prognosis of osteosarcoma with pulmonary metastases at initial presentation is
      not dismal.
AB  - Prognosis of osteosarcoma has been improved markedly with the introduction of
      effective, intensive chemotherapy. However, there are many reports that indicate
      that the prognosis of osteosarcoma with pulmonary metastases at the initial
      presentation is poor. One hundred seventeen patients with osteosarcoma involving
      the extremities were treated at the Chiba Cancer Center from 1976 to 1995. Of
      these, nine (7.6%) patients had pulmonary metastases at initial presentation;
      these nine patients are the subjects of this article. There was an average of 0.9
      pulmonary metastatic lesions at initial presentation seen on plain chest
      radiographs, an average 2.9 lesions seen on computed tomograms of the chest, and
      an average 12.7 lesions found at thoracotomy in these nine patients. The
      pulmonary metastatic lesions that could not be detected by computed tomography of
      the chest were resected by thoracotomy. Three patients died, and six patients are
      alive, with the 5-year survival being 64.8%. Intensive chemotherapy and
      aggressive surgical therapy were done for these patients with osteosarcoma with
      pulmonary metastases at initial presentation, and it is thought that this
      improved the prognosis of these patients. Pulmonary metastases of osteosarcoma at
      initial presentation do not always indicate a hopeless prognosis.

PMID- 9584384
TI  - Benign fetal rhabdomyoma of the upper extremity. A case report.
AB  - Benign fetal rhabdomyoma is a tumor of striated muscle origin that rarely is seen
      in the extremities. Because of the similarities of fetal rhabdomyoma to its
      malignant counterpart, rhabdomyosarcoma, an important distinction is to be made
      to avoid errors in treatment. The clinical presentation, radiographic, and
      pathologic features of the first known case of an isolated upper extremity
      rhabdomyoma are described. The authors discuss, the distinction between this and
      rhabdomyosarcoma and also describe a unique histologic feature in rhabdomyoma,
      the presence of psammoma bodies.

PMID- 9584385
TI  - Healing bone using recombinant human bone morphogenetic protein 2 and copolymer.
AB  - Middiaphyseal 2.5-cm segmental defects in the right femurs of 12 sheep were
      stabilized with stainless steel plates and implanted with (1) 2 mg recombinant
      human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)]
      bioerodible polymer with autologous blood (n = 7), (2) 4 mg recombinant human
      bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] and blood (n =
      3), or (3) poly[D,L-(lactide-co-glycolide)] and blood only (n = 2). Bone healing
      was evaluated for 1 year using clinical, radiographic, gross pathologic, and
      histologic techniques. Union occurred in three sheep in Group 1, two in Group 2,
      and none in Group 3. In the animals that healed, new bone first was visible
      radiographically between Weeks 2 and 6 after implantation; new bone mineral
      content equaled that of the intact femur not surgically treated by Week 16;
      recanalization of the medullary cavity approached completion at Week 52; and at
      necropsy the surgical treated femurs were rigidly healed, the poly[D,L-(lactide
      co-glycolide)] was resorbed completely, and woven and lamellar bone bridged the
      defect site. In two Group 1 sheep euthanized at Weeks 2 and 6, polymer particles
      were permeated by occasional multinucleated giant cells. Some plasma cells,
      lymphocytes, and neutrophils were present locally. The poly[D,L-(lactide-co
      glycolide)] tended to fragment during surgical implantation. Despite these
      observations, the recombinant human bone morphogenetic protein 2/poly[D,L
      (lactide-co-glycolide)] implant was able to heal large segmental bone defects in
      this demanding model.

PMID- 9584386
TI  - Pharmacokinetics of a degradable drug delivery system in bone.
AB  - Local delivery of antibiotics via a degradable carrier has the potential for high
      local antibiotic levels and avoids systemic toxicity. Intravenous access, renal
      function monitoring, and later surgical removal may not be required when
      degradable local delivery modalities are used. This study examined the in vivo
      elution of gentamicin from processed bovine collagen (Type I). Gentamicin
      impregnated collagen (3 mg/kg) was implanted into the femoral medullary canal of
      45 adult white rabbits. The gentamicin was released into the bone and averaged
      greater than 600 micrograms/ml during the initial 48 hours. Local bone levels
      fell to 144.40 +/- 229.84 micrograms/ml at 5 days and were subsequently greater
      than or equal to 10.30 +/- 5.02 micrograms/ml through Day 28. Serum levels
      reached an average peak of 1.25 +/- 0.29 micrograms/ml 5 hours after implantation
      and fell below 1.0 microgram/ml at 12 hours after implantation. Serum levels
      subsequently averaged less than or equal to 0.63 +/- 0.09 microgram/ml through
      Day 28. Collagen impregnated with gentamicin proved to be an effective degradable
      carrier of gentamicin in the healthy rabbit; it provided local bone
      concentrations above the minimum inhibitory concentration of gentamicin and serum
      concentrations below levels associated with systemic toxicity as long as 28 days
      after implantation.

PMID- 9584387
TI  - Evaluation of the mechanical environment during distraction osteogenesis.
AB  - Physical forces have been hypothesized to direct the process of bone regeneration
      during distraction osteogenesis. However, despite significant clinical
      experience, relatively little is known about how the mechanics of distraction
      influence bone formation. This study investigated net fixator forces and strains
      in the distraction callus during bilateral lengthening of tibiae in New Zealand
      White rabbits. Distractions yielded a classic viscoelastic response with a sharp
      increase in fixator force, followed immediately by significant relaxation.
      Tension acting on mesenchymal gap tissue caused by distraction was estimated to
      reach more than 30 N by the time full lengthening was achieved. Average maximum
      cyclic strains within the distraction zone during ambulation were estimated to be
      14% to 15% and supported by the results of fluoroscopic imaging. Paradigms for
      fracture healing have hypothesized that such strains are incompatible with new
      bone formation. The documented clinical success of distraction osteogenesis at
      stimulating large volumes of new bone suggests that other mechanisms that warrant
      additional investigation may be at work during distraction.

PMID- 9584388
TI  - Blood supply of the greater trochanter after trochanterotomy.
AB  - The human vascular anatomy to the greater trochanter after a trochanterotomy
      (digastric, standard) was examined using injection techniques. Three major
      sources of blood supply to the greater trochanter were found: the proximal soft
      tissues, including the gluteus medius and minimus vascularized mainly from the
      internal iliac artery system; the distal soft tissues, including the vastus
      lateralis, vascularized from the descending branches of the lateral circumflex
      femoral artery; and a third possible source of blood circulation came from the
      transverse branch of the lateral circumflex femoral artery. Many vascular
      structures from the lateral circumflex femoral artery were concentrated in the
      anterior half of the vastus lateralis muscle. Perfusion with a latex oxide
      mixture and angiography after trochanterotomy proves that by using a digastric
      trochanterotomy, the transverse and descending branches of the lateral circumflex
      femoral artery to the greater trochanter thus can be preserved. With a standard
      trochanterotomy, the supply from the transverse and descending branches of the
      lateral circumflex artery are lost. These results therefore suggest that a
      digastric trochanterotomy is superior to a standard trochanterotomy because the
      blood supply of the trochanter is preserved.

PMID- 9584389
TI  - Effect of moderate bone hyperthermia on cell viability and mechanical function.
AB  - Extracorporeal hyperthermia treatment of bone followed by its reimplantation may
      be an optional treatment of bone tumors. In this study, the authors examined the
      minimal hyperthermic condition in which complete eradication of all viable cells
      in rat bone can be achieved and the mechanical effect of this treatment on the
      tested bone. When the results were evaluated histologically by special lactate
      dehydrogenase activity staining, it was found that complete bone cell death
      occurred after 30 minutes of heating at 60 degrees C. Cartilage cells, including
      those of the epiphysis, were more resistant to thermal damage. When the ability
      of the specimens to proliferate in cell cultures was tested, no growth was
      observed after heating at temperatures of 50 degrees C or greater. The mechanical
      stiffness tested in the Instron machine showed decreased bone stiffness at 70
      degrees C but no change in the breaking load of the bones. Controlled
      hyperthermia's ability to eradicate viable cells without significant damage to
      the mechanical properties may have clinical relevance in limb salvage tumor
      surgery.

PMID- 9584390
TI  - Biomechanical study of tibialis anterior tendon transfer.
AB  - The tibialis anterior tendon transfer has been used in the treatment of recurrent
      congenital clubfoot and paralytic equinovarus foot deformities in cerebral palsy.
      This study attempts to determine the optimal site of tibialis anterior tendon
      insertion for ankle and foot motion and to compare the split and whole tendon
      transfer. Ten fresh normal anatomic leg specimens were used. The lateral half of
      the tibialis anterior tendon was detached from its insertion, passed beneath the
      extensor retinaculum, and anchored to the appropriate tarsal bone by a barbed
      staple. Tension was applied, and ankle and foot motions were measured. The
      experiment was done by anchoring the tendon to the tarsal bones along the axis of
      the second metatarsal and serially through to the axis of the fifth' metatarsal.
      The entire experiment was repeated using the whole tibialis anterior tendon. For
      split tendon transfer, insertion onto the fourth metatarsal axis was the most
      effective route; it produced maximal dorsiflexion with minimal supination and
      pronation. For whole tendon transfer, the ideal site of insertion was along the
      third metatarsal axis. However, the difference between the average maximum
      dorsiflexion achieved by the split tendon transfer and that of total tendon
      transfer is not statistically significant.

PMID- 9584391
TI  - C fiber responses of wide dynamic range neurons in the spinal dorsal horn.
AB  - Responses of wide dynamic range neurons in the spinal dorsal horn to input from C
      fibers with various conduction velocities were analyzed. The wide dynamic range
      neurons studied were located in the laminae IV-VI of the spinal dorsal horn. The
      C fiber response to stimulation of the superficial peroneal nerve consisted of
      three components: early, middle, and late. The separation into three components
      was found to be caused by asynchronous volleys in three different classes of C
      fibers in the superficial peroneal nerve. The phenomenon of windup was observed
      to occur always in the late component, frequently in the middle component, and to
      a far lesser extent in the early component. The early component was augmented by
      sciatic nerve compression, indicating that the initial part of the C fiber
      response is suppressed within the spinal cord by an inhibitory effect of A fiber
      afferent volleys. An intravenous administration of a specific N-methyl-D
      aspartate receptor antagonist, MK-801 hydrogen maleate, significantly suppressed
      the middle and late components of the C fiber response, although the effect on
      the early component was insignificant. Thus, one can infer that the
      hyperexcitability of wide dynamic range neurons to input from early components of
      cutaneous C fiber stimuli will yield hyperpathic symptoms such as paresthesia,
      hyperalgesia, and allodynia associated with damaged peripheral nerves, and that
      learning how to inhibit the hyperexcitability of wide dynamic range neurons to
      input from early components of C fiber stimuli will lead to the curative
      treatment for neuropathic pain.

PMID- 9584392
TI  - A progressively enlarging soft tissue mass in a 51-year-old man.

PMID- 9584393
TI  - Massive osteolysis after ceramic on ceramic total hip arthroplasty.

PMID- 9584394
TI  - New acetylenes isolated from the bark of Heisteria acuminata.
AB  - Five new linear acetylenic compounds, namely, pentadeca-6,8,10-triynoic acid (1),
      octadeca-8,10,12-triynoic acid (2), trans-pentadec-10-en-6,8-diynoic acid (3),
      cis-hexadec-11-en-7,9-diynoic acid (4), and cis-octadec-12-en-7,9-diynoic acid
      (5), were isolated from the bark of Heisteria acuminata by bioassay-guided
      fractionation, using cyclooxygenase (COX) and 5-lipoxygenase (5-LO) assays as
      models for antiinflammatory activity. The structures of compounds 1-5 were
      established by NMR, MS, IR, and Raman spectroscopy. These isolated compounds were
      found to be potent inhibitors of COX. Compounds 4 and 5 were the most potent
      inhibitors of 5-LO, whereas the other compounds only showed a weak inhibition at
      the same concentration.

PMID- 9584395
TI  - Microbial transformations of hypolipemic E-guggulsterone.
AB  - Biotransformation of E-guggulsterone (pregna-4,17(20)-cis-diene-3,16-dione) (1)
      by Aspergillus niger resulted in the formation of four new hydroxyl derivatives
      identified as 7 beta-hydroxypregna- 4,17(20)-trans-diene-3,16-dione (2), 7 beta
      hydroxypregna-4,17(20)-cis-diene-3,16-dione (3), 7 beta- hydroxypregn-4-ene-3,16
      dione (4), and 7 beta,15 beta-dihydroxypregn-4-ene-3,16-dione (5). The
      biotransformation of 1 with Cephalosporium aphidicola also resulted in the
      formation of four new steroidal derivatives as 11 alpha-hydroxypregna-4,17(20)
      trans-diene-3,16-dione (6), 11 alpha- -hydroxypregna-4,17(20)-cis-diene-3,16
      dione (7), 11 alpha,15 beta-dihydroxypregna-4,17(20)-trans-diene- 3,16-dione (8),
      and 11 alpha,15 beta-dihydroxypregna-4,17(20)-cis-diene-3,16-dione (9). The
      structures of these compounds were elucidated on the basis of 1D and 2D NMR
      spectroscopic techniques.

PMID- 9584396
TI  - Two new mono-tetrahydrofuran ring acetogenins, annomuricin E and muricapentocin,
      from the leaves of Annona muricata.
AB  - Bioactivity-directed fractionation of the leaf extract of Annona muricata L.
      (Annonaceae) has resulted in the isolation of two new Annonaceous acetogenins,
      annomuricine (1) and muricapentocin (2). Compounds 1 and 2 are
      monotetrahydrofuran ring acetogenins bearing two flanking hydroxyl groups;
      however, each has three additional hydroxyl groups. Compound 1 has an erythro 1,2
      diol, and 2 has a 1,5,9-triol moiety. Both 1 and 2 showed significant
      cytotoxicities against six types of human tumors, with selectivities to the
      pancreatic carcinoma (PACA-2) and colon adenocarcinoma (HT-29) cell lines.

PMID- 9584397
TI  - Bioactive kaurane diterpenoids from Annona glabra.
AB  - Phytochemical analysis of the fruits of Annona glabra yielded two new kaurane
      diterpenoids, annoglabasin A (methyl-16 beta-acetoxy-19-al-ent-kauran-17-oate)(1)
      and annoglabasin B (16 alpha-hydro-19-acetoxy-ent-kauran-17-oic acid)(2), along
      with 11 known kaurane derivatives (3-13). The structures of the new compounds
      were established by spectral and chemical evidence. Among these, methyl-16 alpha
      hydro-19-al-ent-kauran-17-oate (11) exhibited mild activity against HIV
      replication in H9 lymphocyte cells, and 16 alpha-17-dihydroxy-ent-kauran-19-oic
      acid (4) showed significant inhibition of HIV-reverse transcriptase.

PMID- 9584398
TI  - Four acylated triterpenoid saponins from Albizia procera.
AB  - Four new oleanane-type triterpene glycosides, proceraosides A-D (1-4), were
      isolated from the seeds of Albizia procera. Their structures were established by
      extensive NMR experiments and chemical methods. Compounds 1-3 comprised acacic
      acid as the aglycon and a monoterpenic carboxylic acid linked to a monoterpene
      quinovoside as the acyl moiety at C-21. The common oligosaccharide moiety linked
      to C-28 in 1-3 was determined as alpha-l-arabino- furanosyl-(1-->4)-[beta-D
      glucopyranosyl-(1-->3)]-alpha-L-rhamnopyranosy l- (1-->2)-beta-D-glucopyranosyl
      ester. These compounds differed in the C-3-linked sugar unit or in the
      configuration of C-6' of the inner monoterpene moiety in the C-21-linked acyl
      unit. Compound 4 was established as the 16-deoxy analogue of 1.

PMID- 9584400
TI  - Mass spectrometry of selected components of biological interest in green tea
      extracts.
AB  - Mass spectrometric methods including EIMS, FABMS, and LC/ESIMS have been surveyed
      as tools for the detection of catechins in extracts of green tea (Camellia
      sinensis). EIMS provide both molecular weight and structure information,
      including epimer differentiation, on compounds 1, 2, and 4 and some structural
      information with compounds 5 and 6. FABMS gives both molecular weight and
      structure information, by an retro-Diels-Alder mechanism, on all compounds.
      LC/ESIMS provides unambiguous molecular weight information on all compounds and
      some additional structural data are evident in the mass spectra of 5 and 6.
      LC/ESIMS is, thus, shown to be an appropriate method for the direct analysis of
      crude extracts of green tea. The information obtained in this work will be of
      importance in future studies involving identification of the components of green
      tea and for characterization of synthetic analogues.

PMID- 9584399
TI  - New compounds with DNA strand-scission activity from the combined leaf and stem
      of Uvaria hamiltonii.
AB  - Two flavanones, hamiltones A (1) and B (2), an aurone, hamiltrone (3), a
      chalcone, hamilcone (4), and a tetrahydroxanthene, hamilxanthene (5), were
      isolated from Uvaria hamiltonii extracts guided initially by fractionation based
      on DNA strand-scission and/or 9KB cytotoxicity assays. Compounds 2-5 have not
      been reported previously, while 1 is new as a natural product. Structural
      assignments were made based on extensive spectroscopic measurements. Compounds 1
      3 were inactive in the 9KB cytotoxicity assay, with compounds 4 and 5 having weak
      activity. In the DNA strand-scission assay, 3 was the most active compound found
      in the DNA strand-scission assay, being 10 times more potent than 1 or 2.
      Compound 4 was only weakly active, and 5 was inactive.

PMID- 9584401
TI  - Cytotoxic scalarane sesterterpenes from a sponge, Hyrtios erecta.
AB  - Novel scalarane sesterterpenes (1-4) were isolated from a sponge, Hyrtios erecta
      (order Dictyoceratida). They were characterized by means of spectral analyses, X
      ray crystallography, and chemical reactions. Compound 1 showed potent in vitro
      and in vivo antitumor activities. In addition, the structure-activity
      relationship was also discussed using computer-assisted structure matching of 1
      and aragusterols.

PMID- 9584402
TI  - Antipoliovirus structure-activity relationships of some aporphine alkaloids.
AB  - A series of 18 aporphinoids have been tested in vitro against human poliovirus.
      The aporphines (+)-glaucine fumarate (1), (+)-N-methyllaurotetanine (4), (+)
      isoboldine (7), and (-)-nuciferine, HCl (10) were found to be active with
      selectivity indices > 14. The nature of the 1, 2-substituents of the isoquinoline
      moiety appeared to be critical for antipoliovirus activity. An SAR study
      demonstrated the importance of a methoxyl group at C-2 on the
      tetrahydroisoquinoline ring for the induction of antipoliovirus activity.
      Molecular modeling of some compounds in this series revealed the close
      similarities between the three-dimensional conformational features of the
      inactive 1,2-substituted derivatives (+)-boldine (6) and (+)-laurolitsine (5)
      with derivatives containing the 1,2-(methylenedioxy) moiety, which were generally
      found to be inactive as exemplified by (+)-cassythicine (9).

PMID- 9584403
TI  - Mediation of the cytotoxicity of lanostanoids and steroids of Ganoderma tsugae
      through apoptosis and cell cycle.
AB  - A new lanostanoid ester glucoside, 3 alpha-acetoxy-5 alpha-lanosta-8,24-dien-21
      oic acid ester beta-d-glucoside (1), and a known steroid, 2 beta,3 alpha,9 alpha
      trihydroxy-5 alpha-ergosta-7,22-diene (2), were isolated from the fruit bodies of
      Ganoderma tsugae and their structures determined by spectroscopic methods. To
      study the cytotoxicity of 1 and 2, the changes of DNA content in human
      hepatocytes (Hep 3B) were studied. A sub-G1 cell stage was drastically increased
      after 24-h incubation with 1 (24 micrograms/mL). Compound 2 (100 micrograms/mL)
      inhibited the cell cycle progression of Hep 3B cells at the G2/M phase with an
      IC50 value of about 87.1 micrograms/mL. These results indicate that 1 causes cell
      death by apoptosis and 2 may possess the activity of cell cycle inhibition.

PMID- 9584404
TI  - Two new C22 1,2-dioxane polyketides from the marine sponge Acarnus cf.
      bergquistae.
AB  - Two new cyclic peroxide-containing polyketide C22 methyl esters, peroxyacarnoic
      acid methyl esters A and B, 1 and 2, have been isolated from the Red Sea marine
      sponge Acarnus cf. bergquistae. Both 1 and 2 are proposed to contain a single 1,2
      dioxane ring, an eneyne functionality, and a terminal double bond or triple bond,
      respectively. The structures were elucidated mainly through 1D and 2D NMR
      spectral analysis.

PMID- 9584405
TI  - Carmabins A and B, new lipopeptides from the Caribbean cyanobacterium Lyngbya
      majuscula.
AB  - Carmabins A and B have been isolated as linear lipotetrapeptides from the BuOH
      extract of the marine cyanobacterium Lyngbya majuscula. The planar structures
      were elucidated by extensive 2D NMR analysis, including 1H-15N HMBC and HMQC
      TOCSY experiments, together with MS measurements.

PMID- 9584406
TI  - Cochinolide, a new gamma-alkylidene bicyclic butenolide with antiviral activity,
      and its beta-glucopyranoside from Homalium cochinchinensis.
AB  - A new gamma-alkylidene bicyclic butenolide designated as cochinolide (1) and its
      beta-glucopyranoside (3) were isolated from the root bark of Homalium
      cochinchinensis (Flacoutiaceae). Their structures, except absolute
      stereochemistries, were determined by spectroscopic means. Cochinolide (1) showed
      moderate antiviral activities against HSV-1 and -2.

PMID- 9584407
TI  - A bioactive secosterol with an unusual A- and B-ring oxygenation pattern isolated
      from an Indonesian soft coral Lobophytum sp.
AB  - A secosterol with a gorgosterol side chain and an unusual oxygenation pattern on
      the A and B rings was isolated from an Indonesian soft coral Lobophytum sp. The A
      and B rings of the reported compound 1 have hydroxyl groups at C-3 and C-7 and an
      epoxide ring at C-5-C-6. The structures of 1 was solved by 2D NMR methods and by
      chemical shift analogy to the known secogorgosterol 2. Compound 1 was found to
      have activity against human ovarian tumor and human leukemia cell lines.

PMID- 9584408
TI  - Novel bioactivities of Curcuma longa constituents.
AB  - Bioassay-directed fractionation of ethyl acetate extract from Curcuma longa Linn.
      rhizomes yielded three curcuminoids, which displayed topoisomerase I and II
      enzyme inhibition activity. Curcumin III (3) was the most active curcuminoid,
      inhibiting topoisomerase at 25 micrograms mL-1. Curcumin I (1) and curcumin II
      (2) inhibited the topoisomerases at 50 micrograms mL-1. Fractionation of the
      volatile oil from the rhizomes afforded ar-turmerone (4), which displayed
      mosquitocidal activity with an LD100 of 50 micrograms mL-1 on Aedes aegyptii
      larvae. Bioassay-directed fractionation of hexane extract from the turmeric
      leaves yielded labda-8(17),12-diene-15,16 dial (5) with antifungal activity
      against Candida albicans at 1 micrograms mL-1 and inhibited the growth of Candida
      kruseii and Candida parapsilosis at 25 micrograms mL-1. In addition, 5 displayed
      100% mosquitocidal activity on A. aegyptii larvae at 10 micrograms mL-1.

PMID- 9584409
TI  - Agelasines H and I, 9-methyladenine-containing diterpenoids from an Agelas
      sponge.
AB  - Two new diterpenes possessing a 9-methyladeninium substituent, agelasines H (5)
      and I (6), along with five related known ones, 1-4 and 7, were isolated from a
      sponge, Agelas sp. The structures of the new compounds were determined from
      spectral data. Compounds 2-4, 6, and 7 exhibited varying degrees of antimicrobial
      activity.

PMID- 9584410
TI  - The hazards of selection.

PMID- 9584411
TI  - In case of emergency.

PMID- 9584413
TI  - Designing for better health.

PMID- 9584412
TI  - Issues in glove selection.

PMID- 9584414
TI  - The birds.

PMID- 9584415
TI  - Interpreting 1910.134.

PMID- 9584416
TI  - [Nerve paralysis after third molar extraction].
AB  - This paper described the incidence of inferior alveolar nerve paralysis following
      surgical removal of impacted third molars. The investigated cases were 789
      patients with 1,299 teeth that were surgically extracted. Eight (0.6%) patients
      had the inferior alveolar nerve paralysis and one (0.08%) had lingual nerve
      paralysis. As for the patients with inferior alveolar nerve paralysis, the
      incidence was 0.4% in those aged 20 to 29 years, 0.6% in those aged 30 to 39
      years, and 3.5% in those aged over 40 years. This study showed that the incidence
      of inferior alveolar nerve paralysis occurred more frequently in older age cases
      and in the cases in which the root splitting or the removing the surrounding bone
      was needed.

PMID- 9584417
TI  - [Anatomical names of foramina and canales in skeleton].
AB  - Latin anatomical names of Foramina and Canales in skeleton were analyzed and
      compared with Japanese anatomical names for better understanding of the
      structures of the human body and for possible revision in the future. The
      conclusions were as follows: 1. In general, short tunnels were called Foramina
      (singular: Foramen), and long tunnels Canales (singular: Canalis). 2. One end of
      Canalis was sometimes called Foramen. In this case, Canalis and Foramen were
      usually modified by the same words. 3. Each name of Foramina contained the word
      which means form, state, absolute size, region of existence, one of the contents
      or function of Foramina. 4. Each name of Canales contained the word which means
      region of existence, one of the contents or function of Canales. 5. Some names of
      Foramina and Canales that were supposed to mean the region of existence meant one
      of the contents of the structures. 6. As for Latin anatomical names, the relation
      between words were relatively clear by the proper use of noun, adjective,
      nominative, and genitive. 7. Since different Chinese characters were sometimes
      pronounced similarly in Japanese anatomical names, different structures might be
      confused. 8. It seemed that some Japanese anatomical names needed partial
      correction.

PMID- 9584418
TI  - [Evaluation of speech quality of skeletal Class III patients before and after
      orthognathic surgery].
AB  - The purpose of this study was to investigate the influence of orthognathic
      surgery on the speech quality of patients with skeletal mandibular protrusion.
      Samples of speech sounds were collected from 10 patients (8 females, 2 males)
      before and after surgical operation. Acoustic analysis, based on the linear
      predictive coding (LPC), was applied to analyze the lowest two local spectral
      peaks (P1, P2) on the vowels. Psychoacoustic examination was also carried out by
      24 examiners using the paired comparison in naturalness of five different words.
      The results were as follows: 1) The widened vowel trajectory after orthognathic
      surgery seemed to be related to improvement of articulatory function. 2) The
      naturalness of speech in psychoacoustic examination has been improved in most
      patients after orthognathic surgery. 3) Patients who have improved naturalness of
      speech showed a tendency of having a widened vowel trajectory.

PMID- 9584419
TI  - [Observation of micrognathic development in mouse fetus induced by
      sulfadimethoxine].
AB  - The purpose of this study was to investigate the process of micrognathic
      development in mouse fetus induced by Sulfadimethoxine (SDM). SDM of 3,000 mg/kg
      was administered orally to pregnant ICR mice on days 8, 9, 10, 11, 12, and 13 of
      gestation. The fetuses were removed on day 15 to analyze the incidence of
      micrognathia. The incidence of micrognathia was the highest in the treated group
      on day 10. The fetuses, SDM-treated on day 10, were sacrificed on days 11, 12,
      13, 14, 15, and 18 and prepared for histological and morphological analyses.
      Histomorphological analyses were performed by lateral and horizontal graphic
      reconstruction using serial frontal sections. It was also performed by clearing
      and alcian blue-alizarin red double staining. In the treated group, bilateral
      sigmoid buckling and shortening of Meckel's cartilage became evident after day
      14, however, the nasal septal and capsule cartilage were less affected. It was
      concluded that remarkable hypoplastic and malformed Meckel's cartilage, caused by
      the administration of SDM, induced mandibular dysmorphogenesis.

PMID- 9584420
TI  - [Characterization of mouse apoptosis signal-regulating kinase 1].
AB  - Apoptosis Signal-regulating Kinase (ASK) 1 was identified that activated two
      different subgroup of MAP kinase kinase (MAPKK), SEK1 (or MKK4), and MKK3/MAPKK6
      (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also
      known as JNK: c-Jun amino-terminal kinase) and p38 subgroup of MAP kinases,
      respectively. It was suggested that ASK1 contributed to cytokine-induced
      apoptosis in some cell lines. In this report, for further investigation about
      roles of ASK1 in mammal, initial characterization of mouse ASK1 was done. The
      mouse cDNA encoding ASK1 was isolated from the mouse kidney cDNA library and the
      overall amino acid sequence similarity between the mouse and the human ASK1 was
      91.9%. A database search revealed that the kinase domain of ASK1 is evolutionally
      well-concervedover species among nematode, fly, mouse, and human. Northern blot
      analysis identified a 6-kb transcript of ASK1 which is expressed in the various
      mouse adult tissues. Immunohistochemical analysis of mouse embryos (17 days post
      coitum) revealed a localized expression of ASK1 in developing skin, cartilage,
      and bone, suggesting a possible role of ASK1 in tissue development during
      embryogenesis as well as cytokine-induced apoptosis.

PMID- 9584422
TI  - [Facilitation of tibialis anterior H reflex and depression of reciprocal Ia
      inhibition on soleus motoneurons during teeth-clenching in man].
AB  - Modulation of the tibialis anterior (T.A.) H reflex and the reciprocal Ia
      inhibition from the ankle flexor to the extensor were studied during voluntary
      teeth-clenching in 7 healthy adult volunteers to investigate the correlation
      between the oral motor activity and the somatic motor function. The T.A. H reflex
      was significantly facilitated during voluntary teeth-clenching, and the amount of
      this facilitation increased with the level of masseter EMG activity. Furthermore,
      the reciprocal Ia inhibition of the soleus H reflex, induced by stimulation of
      the common peroneal nerve at a subthreshold intensity for evoking the T.A. M
      wave, was significantly depressed during voluntary teeth-clenching. It was
      concluded that 1) the T.A. H reflex is facilitated during voluntary teeth
      clenching, 2) there is a positive correlation between the amount of facilitation
      of the T.A. H reflex and the level of teeth-clenching force, and 3) the
      reciprocal Ia inhibition of the crural muscle is reduced during voluntary teeth
      clenching. It was suggested that teeth-clenching contributes to stability of body
      stance by increasing the stiffness of the ankle joint.

PMID- 9584421
TI  - [Fibrinogen affects blood and bone marrow cell functions on titanium in vitro].
AB  - Host-derived blood protein adsorption is much more rapid than the migration of
      cells to foreign surfaces, so the effect of host proteins in blood on blood cells
      and bone marrow cells was investigated by means of in vitro culturing of blood
      and bone marrow cells on titanium. A material preincubated with plasma induced
      high nonspecific esterase (NSE) activity and polymorphonuclear neutrophil (PMN)
      elastase activity, but neither a serum- nor albumin-coated material had the same
      effect as the plasma-coated material. Therefore, attention was paid to
      fibrinogen. On titanium coated with fibrinogen increases in not only NSE activity
      and PMN elastase activity in blood and bone marrow, but also tartrate-resistant
      acid phosphatase (TRACP) activity were observed in bone marrow cultures. A
      decrease in alkaline phosphatase (ALP) activity was also observed in the
      cultures. These changes of bone marrow cultures were reversed by the addition of
      recombinant human bone morphogenetic protein-2 to the cultures. These results
      suggested that bleeding around titanium affects the function of macrophages or
      neutrophils due to the effect of fibrinogen. Furthermore, it was suggested that
      this factor may affect the functions of osteoblasts anti osteoclasts around a
      titanium implant with the inevitable side effects of implantation in bone tissue:
      bleeding and clotting.

PMID- 9584423
TI  - [Induction of rhythmical activity in digastric muscles in an in vitro brainstem
      preparation from adult mice].
AB  - In this study, it was attempted to induce masticatory movements in an in vitro
      brainstem-spinal cord preparation isolated together with the orofacial structure
      from adult mice. The preparation was perfused intra-arterially with an artificial
      cerebrospinal fluid (ACSF) containing dextran through a cannula fixed to the
      descending aorta, and was placed in a bath perfused with the ACSF. Repetitive
      electrical stimulation of the medullary pyramidal tract (MPT) induced rhythmic
      EMG activities in the digastric muscle (3.8-7.2 Hz). Bath and intra-arterial
      application of kynurenic acid (KYN) or D, L-2-amino-5-phosphonovaleric acid (APV)
      suppressed the rhythm. During application of KYN, the rhythmic EMG activity in
      the digastric muscle could not be induced, even though the intensity of
      stimulation was raised. On the other hand, during application of APV, stimulation
      at a higher intensity induced rhythmic EMG activities with a lower frequency and
      a smaller amplitude. The results showed that glutamate is involved in induction
      of the rhythmic EMG activities by stimulation of the MPT, and that excitatory
      effects via the N-methyl-D-aspaltic acid receptor is not indispensable for its
      induction.

PMID- 9584424
TI  - [Electromyographic power spectral analysis of sternocleidomastoid muscle during
      sustained voluntary clenching].
AB  - The purpose of this study was to investigate the changes of the activity of the
      sternocleidomastoid (SCM) muscles during sustained voluntary clenching. Ten
      healthy male subjects without any occlusal functional problems were asked to
      clench as long as possible in the intercuspal position while keeping the
      electromyographic activity of the masseter muscle at the 50% maximum voluntary
      contraction. Frequency analysis was carried out by computer using a fast Fourier
      transform algorithm to obtain the power spectrum of the SCM muscle during the
      fatiguing process and the recovery process. The results were as follows: 1.
      Sustained activities of the SCM muscles were observed during sustained voluntary
      clenching. 2. The power spectra of the SCM muscles significantly shifted to a
      lower frequency as time elapsed. 3. The power spectra of the SCM muscles obtained
      three minutes after relaxation recovered to those of the beginning of clenching.
      These findings indicated that muscle fatigue may be induced in the SCM muscle
      during sustained voluntary clenching and that electromyographic power spectral
      analysis can be used as a noninvasive, objective, and quantitative index of SCM
      muscle fatigue.

PMID- 9584425
TI  - [Investigation of metal allergy to constituent elements of intraoral restoration
      materials].
AB  - Allergies caused by metals have been increasing. The number of patients visiting
      dentists with the chief complaint of metal allergy has also been increasing. From
      March 1994 to February 1997, 263 patients who complained of various symptoms
      visited our allergy clinic. Among them, 184 patients were suspected to have
      allergy caused by metals in dental restoration materials and were referred to the
      patch test. Among 165 patients', 128 were positives for metal allergy.
      Constituent elements of intraoral metals were analyzed in 107 of these 128
      positive patients. The findings were as follows: 1. The most common five elements
      acting on the patients were Hg, Co, Ni, Cr, and Pd. 2. The most frequently used
      elements of dental restoration metal materials were Zn, Ag, Cu, Au, and Pd, and
      the alloy was Au-Ag-Pd alloy. 3. The highest tendency of coincidence between
      allergen and intraoral metals were observed among Co-Cr-Ni alloys and Pd, Ni, and
      Cr elements. 4. In case of palmoplantar pustulosis, allergen metals tended to be
      the same as intraoral metal elements.

PMID- 9584426
TI  - [Influence of covering gingival sulcus with denture base on periodontal tissue-
      pH value in gingival sulcus and amount of gingival crevicular fluid].
AB  - The purpose of this study was to clarify the effect of covering gingival sulcus
      with denture base on periodontal tissue. Six subjects participated in this study.
      An experimental denture was inserted to a test tooth of each subject that was
      prepared for a full crown. Each experimental denture was designed to cover the
      gingival sulcus around the tooth. All subjects used them for two weeks. The
      parameters were as follows: 1) pH in gingival sulcus, 2) amount of gingival
      crevicular fluid, 3) tooth mobility, 4) temperature in gingival sulcus, 5)
      probing depth, 6) GI, and 7) P1I. Measurements were performed during the
      following periods: 1) pre-examination, 2) after cementation of provisional
      restoration, 3) during insertion of experimental denture, 4) after cementation of
      final restoration. A repeated-measures ANOVA was used for statistical analysis.
      The results were as follows: 1. pH value and amount of GCF increased after
      insertion of the experimental denture, and returned to same level as pre
      examination after cementing of the final restoration. 2. Tooth mobility decreased
      during insertion of the experimental denture. 3. The changes of the other
      parameters were not significant. These results suggested that subclinical
      inflammatory change occurred in periodontal tissue in an early stage accompanied
      with covering of the gingival sulcus.

PMID- 9584427
TI  - [Bone mineral density (BMD) distribution in edentulous mandible--a measuring
      system for bone mineral content with computed radiography (CR)].
AB  - The purpose of this study was to develop a measuring system for bone mineral
      density(BMD) using computed radiography and to measure BMD distribution in the
      edentulous mandible. Nine 2-3 mm thick sequential cross-sectional bone slices
      were obtained from five cadaveric mandibles. Each slice in cross-sectional view
      on X-ray image was divided into 64 elements and BMD distribution was
      investigated. The results were as followed: 1. BMD measuring system: The accuracy
      was 1.4%(relative error) and the reproducibility was 1.1%(CV). 2. BMD
      distribution in edentulous mandible: 1) BMD varied from slice to slice,
      decreasing from anterior to posterior in both cortical and cancellous bone on the
      inferior and lingual side. The BMD of buccal cancellous bone was relatively
      higher than that of the lingual side and remained fairly constant throughout. The
      BMD of buccal cortical bone showed a slight posterior increase. 2) Greater
      individual variation of BMD was observed near mental foramen and in incisor
      lingual and inferior cancellous bone. Our system demonstrated excellent precision
      and reproducibility BMD distribution varied near regions of muscle attachment and
      the mandibular canal. Further, it was suggested that strong implant stability in
      the molar region may be obtained by installation of the fixtures in the buccal
      cancellous area.

PMID- 9584428
TI  - Generalizing everyday memory: signs and handedness.
AB  - Memory for frequently encountered road signs was investigated. In Experiment 1,
      the average level of recall of road sign features was found to be only 47%. In
      Experiment 2, more left-handed than right-handed people recalled that a walking
      figure faces right on one sign, whereas more right-handed than left-handed people
      recalled that a digging figure faces left on another sign. Performance thus
      reflected not a difference in level of mnemonic ability between left-handed and
      right-handed groups but instead the compatibility between group and task. In
      Experiment 3, participants were asked to draw any figure walking and any figure
      digging, with a pattern of results similar to that of Experiment 2. It is
      suggested that handedness effects in recall are mediated by motor imagery.

PMID- 9584429
TI  - Training on integrated versus separated Stroop tasks: the progression of
      interference and facilitation.
AB  - Two experiments examined the course of interference and facilitation in the
      Stroop (1935) task during training. Two versions of the task were compared:
      integrated (e.g., the word RED in the color green) and separated (e.g., green
      asterisks above the word RED). Stimuli were congruent (RED in red), incongruent
      (GREEN in red), or neutral (XXX in red). Over 5-day (Experiment 1) and 10-day
      (Experiment 2) training sessions, facilitation due to congruence was small,
      stable, and equivalent in both task versions. In contrast, interference declined
      sharply on the integrated task over Days 1-3, then slowed to parallel the gradual
      decline on the separated task. Finally, training on the color naming task did not
      affect a word reading task administered after training. These findings imply that
      (a) Stroop interference initially reflects two problems--overcoming integration
      and managing two conflicting information sources; (b) with practice, the larger
      integration problem is solved relatively quickly, rendering the integrated and
      separated tasks quite comparable thereafter; and (c) facilitation and
      interference in the Stroop task may be independent. These results challenge
      extant theories of the Stroop effect, which do not predict such effects.

PMID- 9584430
TI  - Presenting two incongruent color words on a single trial does not alter Stroop
      interference.
AB  - Two experiments showed that having two incongruent words present on a single
      Stroop trial (e.g., both red and green in blue, say "blue") did not alter
      interference relative to having only one incongruent word. This was true whether
      the two incongruent words were presented successively at several stimulus onset
      asynchronies (Experiment 1) or simultaneously in adjacent positions (Experiment
      2). We argue that the first word captures attention and "locks out" others,
      preventing additional interference.

PMID- 9584431
TI  - Retrieval processes that produce interference in modified forced-choice
      recognition tests.
AB  - Recognition can suffer if the retrieval cues activate more than one trace (e.g.,
      for Flower A and Flower A'). We found evidence for two retrieval processes by
      examining interference effects in forced-choice tests (e.g., "Did you see Flower
      A or Flower A"?). Experiment 1 provided evidence of a problem in discriminating
      between temporally and contextually similar traces that were formed in the study
      phase. A competitor (Flower A') interfered more if it was shown in the study
      phase rather than in the test phase. Experiments 2 and 3 found evidence for a
      blocking process in recognizing pairs of words (child-apple). A competitor
      interfered more if it was recent, shown at test rather than at study. This
      pattern occurred regardless of whether the competitor was similar to the target
      (child-orange) or dissimilar to it (child-truck). The importance of a particular
      retrieval process may depend on an item's representation as well as on the
      retrieval cues.

PMID- 9584432
TI  - Resource allocation during the rereading of scientific texts.
AB  - Two experiments examined how cognitive resources are allocated to comprehension
      processes across two readings of the same scientific texts. In Experiment 1,
      readers read and later reread texts describing scientific topics. The results
      indicated that across readings, readers decreased resources allocated to
      proposition assembly, increased resources allocated to text-level integration,
      and expended a similar amount of resources to lexical access. Subjects who reread
      the texts after a week delay showed a similar pattern, except that they did not
      show the increase for text-level integration. Experiment 2 revealed a similar
      pattern of results with a moving window procedure, except that there was a
      significant decrease in resources allocated to lexical access across exposures.
      This experiment also indicated that the rereading speedup was greatest at
      sentence boundaries, suggesting that the prior exposure enabled readers to
      immediately process each word. Overall, the results are consistent with the claim
      that readers allocate proportionally more available resources to text-level
      integration during rereading because proposition assembly, which enables text
      level integration, can be completed with fewer resources.

PMID- 9584433
TI  - The representation of space in mental models derived from text.
AB  - Mental models of text are representations of what the text is about (i.e.,
      situations), rather than representations of the text itself. Many mental model
      theories propose that mental models, like real situations, are played out in a
      medium analogous to a Euclidean space so that distance has functional
      consequences. For example, when one mentally manipulates one element of the
      representation, one will notice other elements that are spatially close to it,
      and this will enhance their short-term accessibility. In a test of this noticing
      hypothesis, participants read texts that described the object-by-object
      construction of a spatial layout. According to the text, a critical object ended
      up close to a target object (in the spatial layout) or far from the target
      object. In neither case, however, was the relation between the critical object
      and the target object explicitly described in the text. The noticing hypothesis
      predicts that the accessibility of the target object will be enhanced when the
      critical object is close to it. We tested this prediction in seven experiments in
      which we also manipulated the number of objects described, whether the
      description was accompanied by a diagram, the presentation modality of the
      description, the number of dimensions in the spatial layout, and the measurement
      of accessibility. We failed to find consistent support for the noticing
      hypothesis. The data compel the conclusions that (1) spatial representations can
      be formed when one is reading, (2) these representations do not support automatic
      noticing of implicit spatial relations, (3) it is likely that the spatial
      representation is more topological or functional than Euclidean.

PMID- 9584434
TI  - Serial attention within working memory.
AB  - It is proposed that people are limited to attending to just one "object" in
      working memory (WM) at any one time. Consequently, many cognitive tasks, and much
      of everyday thought, necessitate switches between WM items. The research to be
      presented measured the time involved in switching attention between objects in WM
      and sought to elaborate the processes underlying such switches. Two experiments
      required subjects to maintain two running counts; the order in which the counts
      were updated necessitated frequent switches between them. Even after intensive
      practice, a time cost was incurred when subjects updated the two counts in
      succession, relative to updating the same count twice. This time cost was
      interpreted as being due to a distinct switching mechanism that controls an
      internal focus of attention large enough for just one object (count) at a time.
      This internal focus of attention is a subset of WM (Cowan, 1988). Alternative
      visual and conceptual repetition-priming and memory retrieval explanations for
      the cost involved in switching between items in WM are addressed.

PMID- 9584435
TI  - Nonverbal working memory of humans and monkeys: rehearsal in the sketchpad?
AB  - Investigations of working memory tend to focus on the retention of verbal
      information. The present experiments were designed to characterize the active
      maintenance rehearsal process used in the retention of visuospatial information.
      Rhesus monkeys (Macaca mulatta; N = 6) were tested as well as humans (total N =
      90) because these nonhuman primates have excellent visual working memory but,
      unlike humans, cannot verbally recode the stimuli to employ verbal rehearsal
      mechanisms. A series of experiments was conducted using a distractor-task
      paradigm, a directed forgetting procedure, and a dual-task paradigm. No evidence
      was found for an active maintenance process for either species. Rather, it
      appears that information is maintained in the visuospatial sketchpad without
      active rehearsal.

PMID- 9584436
TI  - Prospective memory: when reminders fail.
AB  - A frequent assumption in the area of prospective memory is that a reminder to do
      an activity in the future improves the likelihood of doing the activity. The
      results of four experiments indicated, however, that the most general version of
      this assumption is incorrect. Subjects were either reminded of a prospective
      memory task several times during a retention interval or not reminded of the
      prospective memory task. The most effective reminders referred both to the
      prospective memory target events and to the intended activity. Reminders that
      referred only to the target events did not improve prospective memory (relative
      to a no-reminder control). Reminders that referred only to the intended activity
      did improve prospective memory, but not to the level of reminders that referred
      both to the target events and to the intended activity. Instructions to imagine
      oneself performing the prospective memory task did not further improve
      prospective memory. Neither the delay between the prospective memory instructions
      and the prospective memory cover task nor the delay between a reminder and a
      prospective memory target event significantly influenced performance. The
      results, which are discussed in terms of theoretical and practical implications,
      support a new theory of prospective memory and suggest surprising conditions
      under which reminders fail to benefit prospective memory.

PMID- 9584437
TI  - The detection model of recognition using know and remember judgments.
AB  - The signal detection model for know and remember recognition judgments was tested
      in two experiments. In Experiment 1, two predictions of the model were tested:
      (1) that measures of memory sensitivity, A', are equivalent in value when based
      on either the recognition (know or remember) criterion or on the remember
      criterion; and (2) that there is a positive correlation between recognition bias
      and the proportion of know judgments that are hits, but no correlation between
      recognition bias and proportion of remember hits (Donaldson, 1996). Both
      predictions were supported by the data. In Experiment 2, the context of test
      items was manipulated to make it more or less similar to learning context. The
      detection model requires that memory sensitivity be the same for both recognition
      and remember judgments, regardless of test context. Alternatively, if remember
      judgments reflect only the retrieval of episodic information from memory, the two
      measures of memory sensitivity should become more disparate in value as learning
      and test context are made more similar. Memory sensitivity was generally the same
      in value for recognition and remember criteria but different across context
      conditions, thus supporting the detection model. The nature of the memory
      continuum used in detection theory is also discussed.

PMID- 9584438
TI  - Retrieving names in old age: short- and (very) long-term effects of repetition.
AB  - Two experiments are reported that examine the effects of repetition on name
      retrieval in younger adults (in their 50s and 60s) and older adults (in their 70s
      and 80s). In Experiment 1, the subjects were asked to name a set of famous faces
      four times over the course of a 1-h session. Younger subjects produced
      significantly more correct responses than did older subjects. There was
      significant improvement with repeated attempts at naming, with younger and older
      subjects benefiting equally in terms of increasing numbers of correct responses
      across the session. In contrast, there was a highly significant age deficit in
      picture recognition over a similar retention interval. A qualitative analysis of
      naming responses (full name vs. part of the name) provided support for the view
      that aging and nonrecent use have equivalent effects on retrieval. In Experiment
      2, younger subjects (but not older subjects) were significantly more likely to
      correctly name famous faces that they had seen 22 months previously than to
      correctly name new famous faces. In contrast, older subjects (but not younger
      subjects) were significantly more likely to produce erroneous names to famous
      faces that they had seen 22 months previously than to new famous faces. It is
      concluded that repetition priming may be relatively unaffected by aging over
      short retention intervals (Experiment 1) but not over a very long retention
      interval (Experiment 2).

PMID- 9584439
TI  - On forgetting the historical past.
AB  - In this paper, empirical data are presented related to memory and time
      perception. The data are the frequencies with which specific calendar years are
      cited in newspaper texts. When plotted, the curves produced by the time series of
      these frequencies turn out to be independent of the languages and cultures in
      which the texts have been written as well as the year and the year density of the
      text corpus. The frequency of a specific year is inversely proportional to the
      distance from that year to the year in which the texts were written. It is argued
      that these curves are forgetting curves. It is suggested that the curves might be
      explained in terms of the "cognitive distance" between past and present. An
      argument is presented based on the curve representing the frequencies with which
      future years are cited in newspaper texts.

PMID- 9584440
TI  - Recall of short word lists presented visually at fast rates: effects of
      phonological similarity and word length.
AB  - Phonological similarity of visually presented list items impairs short-term
      serial recall. Lists of long words are also recalled less accurately than are
      lists of short words. These results have been attributed to phonological recoding
      and rehearsal. If subjects articulate irrelevant words during list presentation,
      both phonological similarity and word length effects are abolished. Experiments 1
      and 2 examined effects of phonological similarity and recall instructions on
      recall of lists shown at fast rates (from one item per 0.114-0.50 sec), which
      might not permit phonological encoding and rehearsal. In Experiment 3, recall
      instructions and word length were manipulated using fast presentation rates. Both
      phonological similarity and word length effects were observed, and they were not
      dependent on recall instructions. Experiments 4 and 5 investigated the effects of
      irrelevant concurrent articulation on lists shown at fast rates. Both
      phonological similarity and word length effects were removed by concurrent
      articulation, as they were with slow presentation rates.

PMID- 9584441
TI  - Irrelevant speech eliminates the word length effect.
AB  - The word length effect refers to the observation that memory is better for short
      than for long words. The irrelevant speech effect refers to the finding that
      memory is better when items are presented against a quiet background than against
      one with irrelevant speech. According to Baddeley's (1986, 1994) working memory,
      these variables should not interact: The word length effect arises from rehearsal
      by the articulatory control process, whereas irrelevant speech reduces recall
      through interference in the phonological store. Four experiments demonstrate
      that, like articulatory suppression, irrelevant speech eliminates the word length
      effect for both visual and auditory items. These results (1) provide further
      evidence against the ability of working memory to explain the word length and
      irrelevant speech effects and (2) confirm a specific prediction of Nairne's
      (1990) feature model.

PMID- 9584442
TI  - From algorithmic computing to direct retrieval: evidence from number and
      alphabetic arithmetic in children and adults.
AB  - A number of theories of mental arithmetic suggest that the ability to solve
      simple addition and subtraction problems develops from an algorithmic strategy
      toward a strategy based on the direct retrieval of the result from memory. In the
      experiment presented here, 2nd and 12th graders were asked to solve two tasks of
      number and alphabet arithmetic. The subjects transformed series of 1 to 4 numbers
      or letters (item span) by adding or subtracting an operand varying from 1 to 4
      (operation span). Although both the item and operation span were associated with
      major and identical effects in the case of both numbers and letters at 2nd grade,
      such effects were clearly observable only in the case of letters for the adult
      subjects. This suggests the use of an algorithmic strategy for both types of
      material in the case of the children and for the letters only in the case of the
      adults, who retrieved numerical results directly from memory.

PMID- 9584443
TI  - Rule- and idiosyncratically derived denominal verbs: effects on language
      production and comprehension.
AB  - A distinction is drawn between two classes of denominal verbs, and four
      experiments examine the effects of this distinction on the production and
      comprehension of denominalizations. Rule-derived (RD) denominals are formed from
      nouns belonging to semantic categories whose members share the same meaning when
      they are used as verbs. For instance, denominal verbs formed from vehicles
      generally mean "to travel/convey by x," where x represents the specific vehicle.
      In contrast, idiosyncratically derived (ID) denominals are drawn from categories
      whose members possess diverse meanings when they are used as verbs. Thus, to fish
      means "to try to catch fish," whereas to dog means "to chase tirelessly." Because
      the verb meanings of rule-derived terms are relatively predictable, they might be
      more easily produced and understood. Experiments 1 and 2 show that speakers are
      more likely to select RD terms for denominalization and are faster at creating
      denominal uses for RD terms. Experiments 3 and 4 show that RD denominals are
      rated as easier to understand than ID denominals, and that they are interpreted
      more uniformly across readers. The Discussion considers pragmatic accounts of the
      results, the theoretical basis for the distinction between RD and ID terms, and
      the more general point that experimental methods can be used to study creative
      uses of language.

PMID- 9584444
TI  - Impact of intuitive theories on feature recruitment throughout the continuum of
      expertise.
AB  - Expertise in object domains involves both the perceptual learning of the
      differentiating and higher order features that are indicative of concepts and the
      elaboration of intuitive theories. Triad-similarity judgments, feature-salience
      ratings, and verbal protocols were used to investigate the effects of theories on
      the recruitment of features across different categorization contexts, as well as
      the degree to which expert categorization skills transferred to less familiar
      domains. Whereas novices considered features that indicated overall similarity to
      be more perceptually salient than were modified parts that indicated taxonomic
      relations, experts found them equally salient. Experts' theories were
      instrumental in directing feature recruitment in contexts involving
      identification, image generation, and similarity decisions. Experts' theories
      also supported the transfer of categorization skills to related, less familiar
      domains. The relation of mutual dependence between perceptual learning and theory
      development throughout the continuum of expertise is considered.

PMID- 9584445
TI  - Implicit learning of complex structures: active adaptation and selective
      processing in acquisition and application.
AB  - Subjects exposed to members of a structured domain become sensitive to the
      general structure of that domain, even when they are unaware that the domain has
      such structure (e.g., Reber, 1993). Numerous investigators have attempted to
      characterize this learning as unselective in acquisition and automatic in
      application. However, we contend that this characterization miscasts the
      fundamental nature of learning. In a series of experiments, we demonstrate that
      what subjects learn implicitly about the structure of a domain critically depends
      on decisions they make about how to organize the structural components.
      Similarly, the application of knowledge gained implicitly is not stable, but may
      be selected or even created under the demands of the test task. We conclude that
      implicit learning, just like explicit learning, proceeds through active
      organization of the stimulus complex, rather than by passively absorbing any
      level of structure. We propose a synthesis, in which learning, with and without
      awareness, is understood through a common set of principles.

PMID- 9584446
TI  - Enforcing the Fourteenth Amendment: city of Boerne v. Flores and the Americans
      with Disabilities Act.

PMID- 9584447
TI  - The early days of the dental research unit.

PMID- 9584448
TI  - Dental research and the Medical Research Council.

PMID- 9584449
TI  - History of the DDE indices.

PMID- 9584450
TI  - Plaque minerals and dental caries.
AB  - Studies to date show that extracellular fluid obtained from resting plaque is
      highly supersaturated with respect to enamel mineral and that, after one sugar
      rinse, it rarely becomes unsaturated, even though the pH decreases markedly. This
      is partly because Ca2+ is released from plaque pools and minimises the change in
      saturation level, that is, acts as a "saturation buffer". Theoretical
      considerations, however, suggest that, with repeated pH cycling, calcium and
      possibly phosphate and fluoride pools in plaque will become depleted, at which
      time a state of marked undersaturation of plaque fluid will appear when the pH
      decreases on glycolysis. Such plaque fluid would have a high demineralisation
      potential. An artificial solid-phase supplement of the ion reservoirs in plaque
      would be expected to delay the time when plaque fluid becomes unsaturated during
      multiple pH cycling events, and would be expected to have marked anti-caries
      effects.

PMID- 9584451
TI  - Plaque mineralisation in vitro.
AB  - Dental calculus is plaque mineralised by deposition of calcium and phosphate
      resulting from interactions between the oral microbial plaque flora and
      components of oral fluids. An artificial-mouth microcosm dental plaque culture
      system has been developed to study aspects of plaque mineralisation, including pH
      control. Five plaques were grown from saliva under simulated oral conditions in a
      mucin-containing medium, and sucrose was applied to mimic meals. The plaques were
      mineralised with a urea-based, calcium-phosphate-monofluorophosphate-urea (CPMU)
      mineralising solution. Alkaline pH oscillations were generated by the plaques in
      response to CPMU applications, and an acidic oscillation followed sucrose
      applications. Plaque mineralisation by the CPMU procedure was almost totally
      dependent on the urea present in the mineralising solution, but total
      mineralisation also increased as the resting pH increased as a result of urea in
      the medium. Following four CPMU applications with a sucrose application every 12
      hours improved plaque viability and mineralisation. The plaque mineral formed
      resembled a carbonated hydroxyapatite; other potential calcium phosphate minerals
      were undetectable except for calcium carbonate. A wide range of mineral
      deposition patterns in plaque were seen by electron microscopy.

PMID- 9584452
TI  - Enamel--an overview.

PMID- 9584453
TI  - The changing focus of chronic temporomandibular disorders: management within a
      hospital-based, multidisciplinary pain centre.
AB  - Despite evidence to the contrary, many dentists still cling to outdated beliefs
      and practices regarding the aetiology and management of chronic temporomandibular
      disorders (TMDs). Chronic pain disorders require a multidisciplinary approach
      with a strong focus on psychological factors. Treatment failures and relapse are
      likely if such factors are not considered. Most chronic temporomandibular pain
      problems are extracapsular and of myofascial origin. Mechanistic or invasive
      treatments in such cases may be inappropriate and can cause harm. Conservative
      measures used for other types of chronic muscular pain are generally recommended.
      All health practitioners who deal with acute and chronic pain should be aware of
      recent major advances in the understanding of pain mechanisms. Along with
      psychosocial considerations, these must be emphasised in undergraduate and
      continuing education programmes.

PMID- 9584454
TI  - Antibiotic cover following joint replacement.

PMID- 9584455
TI  - [Echo-planar FLAIR imaging in patients with brain disorders: comparative studies
      with turbo-SE T2WI and turbo-FLAIR].
AB  - Fluid-attenuated inversion-recovery (FLAIR) imaging is a technique that produces
      heavily T2-weighted CSF-nulled images by coupling an inversion pulse followed by
      long inversion time (TI) to a long echo time (TE) readout. With nulling of the
      CSF, a tissue abnormality usually becomes the brightest object in the image,
      thereby improving lesion detection in the brain. The FLAIR technique is also
      easily adapted to echo-planar imaging (EPI), the most rapid MR imaging technique
      available. We examined EPI-FLAIR imaging in patients with brain disorders and
      compared the results with those of turbo-FLAIR and turbo SE T2-weighted imaging.
      MR imaging was performed on a 1.5 T imager in 29 patients with cerebral
      infarction and 2 patients with multiple sclerosis. The turbo-SE T2-weighted
      sequence parameters used were: TR/TE = 4000 ms/99 ms, total scan time = 2 min 12
      sec. Turbo-FLAIR sequence parameters were TR/TE/TI = 9000 ms/119 ms/2200 ms,
      total scan time = 4 min 3 sec. EPI-FLAIR sequence parameters were TE/TI = 60
      ms/2200 ms, total scan time = 4.38 sec. EPI-FLAIR images were compared
      quantitatively and qualitatively with both turbo-FLAIR and turbo-SE T2-weighted
      images. In the quantiative comparisons of EPI-FLAIR images with turbo-FLAIR and
      turbo-SE T2-weighted images, lesion-to-white matter contrast and the C/N ratio of
      EPI-FLAIR images were found to be significantly inferior to both turbo-FLAIR and
      turbo-SE T2-weighted images (P < 0.001). In the qualitative comparisons, the
      lesion detection and conspicuty of EPI-FLAIR images were inferior to those of
      turbo-FLAIR and turbo-SE T2-weighted images. In conclusion, the image quality of
      EPI-FLAIR images was inferior to that of both turbo-FLAIR and turbo SE T2
      weighted images. EPI-FLAIR should not replace turbo-FLAIR.

PMID- 9584456
TI  - [In vitro study of ultrasonic bone densitometry using dissected calcaneus].
AB  - Quantitative ultrasound (QUS) of the calcaneus is a widely utilized method for
      bone densitometry. However, the meaning of measured parameters, such as speed of
      sound (SOS) and broadband attenuation (BUA), is not well established. We
      performed in vitro measurement of dissected human calcaneus (n = 60; male 29,
      female 31; mean age 81 years) using two QUS machines and also measured bone
      densities using SXA, DXA and pQCT. Finally, we investigated breaking strength of
      the calcaneus and studied the correlation with QUS parameters and other assessed
      parameters. The two QUS measurements were in good agreement in most experiments.
      SOS correlated most closely with bone mineral densities assessed by pQCT and did
      not correlate with factors related to bone size, while BUA showed the highest
      correlation with BMC and association with parameters related with bone size such
      as bone area and bone width. With maximal breaking stress of the calcaneus,
      correlations were almost equal among QUS parameters and bone mineral density. We
      conclude that SOS is the parameter most closely associated with true bone mineral
      density (g/cm3), whereas BUA represents both bone mineral density and bone size,
      mimicing BMD assessed by DXA or SXA.

PMID- 9584457
TI  - [Relationship between water content and magnetization transfer ratio in the rat
      brain using a new cardiac perfusion model with different osmotic gradients].
AB  - We devised a method to make a gradient water content model of the rat brain by
      perfusing osmotic NaCl solution from the left ventricule. Using this model we
      measured the water content and magnetization transfer ratio (MTR) of the frontal
      lobe and the pons as examples of gray and white matter, respectively. When we
      perfused five levels of osmotic NaCl solution (0, 0.9, 1.8, 3.6 and 7.2%) to
      respective groups of four rats, mean water content decreased from 81.5% at 0% to
      75.9% at 7.2% NaCl in the frontal lobe and from 74.1% to 61.0% in the pons, while
      MTR increased from 21.5% to 24.2% in the frontal lobe and from 22.9% to 27.3% in
      the pons. Thus water content was significantly higher (p < 0.01) in the frontal
      lobe than the pons at each level of NaCl concentration, and MTR was significantly
      higher in the pons than the frontal lobe (p < 0.05 approximately 0.01, except at
      0%). Further, the grade of alteration was higher in the pons than the frontal
      lobe for both water content and MTR. Excellent correlations between MTR and water
      content were observed with coefficients of -0.75 and -0.82 for the frontal lobe
      and pons, respectively, and the regression lines showed higher position and slope
      in the frontal lobe than the pons. From these results we concluded that the pons
      is rich in free water of extracellular fluid that moves easily between the myelin
      sheath, whereas in the frontal lobe, water is so diffusely mingled with membranes
      and favorable to bound water that the magnetization transfer effect is more
      effective, yielding a higher MTR for the same water content and showing greater
      change in MTR for the same change in water content as the pons.

PMID- 9584458
TI  - [The usefulness of fractal geometry for the diagnosis of small peripheral lung
      tumors].
AB  - PURPOSE: To assess the usefulness of fractal geometry in quantitatively
      evaluating the convergence of peripheral vessels on peripheral lung tumors in
      maximum intensity projection (MIP) images. MATERIALS AND METHODS: We studied the
      MIP images of 34 pathologically proved small peripheral lung tumors (lung cancer
      in 21, hamartoma in 13) in 34 patients. To obtain MIP images, spiral CT (SOMATOM
      PLUS; Siemens) was performed during a single breath hold (24-second scan time, 2
      mm section thickness, and 2 mm/sec table feed time, reconstructed at 1-mm
      increments). To evaluate the convergence of the peripheral vessels and bronchi
      towards the tumor, we fixed a region of interest (ROI) on the hilar side of the
      lung tumor, parallel to the chest wall, which consisted of 64 x 64 square pixels,
      in the images that divided at the center of the window width. We counted the
      overlapping pixels by the two-dimensional box-counting method and obtained
      fractal dimensional data on lung cancers and hamartomas. RESULTS: There was a
      statistically significant difference in the fractal dimension (D) between lung
      cancers (D = 1.81 +/- 0.13) and hamartomas (D = 1.67 +/- 0.10) (P = 0.0067).
      CONCLUSION: Fractal geometry could be useful in the diagnosis of small peripheral
      lung tumors.

PMID- 9584459
TI  - [Prognosis of residual spleen after partial splenic embolization for the
      treatment of hypersplenism in cirrhosis].
AB  - The aim of this study was to elusidate the change in residual spleen volume after
      partial splenic embolization (PSE) in 43 cirrhotic patients with marked
      hypersplenism. Residual spleen volume was indicated as the rate (%) of residual
      spleen to initial spleen before PSE. Furthermore, the platelet count after PSE
      was observed in 23 patients followed up for 2 years. Residual spleen volume in
      patients with infarction rates of more than 80% (group A) had been maintained
      within 20 % even after 2 years, while they had obviously increased during the
      early stage after PSE in patients with infarction rates under 80% (group B),
      especially in patients with lower infarction rates (under 60%). Mean platelet
      count improved significantly in both groups after PSE (p < 0.001, respectively),
      but increased more in group A than in group B (p < 0.01). High fever and
      abdominal pain were observed in all cases of PSE. Other adverse effects such as
      pleural effusion and ascites that were frequent in group A were transient. These
      results suggest that PSE performed with a high infarction rate of the spleen
      provides effective, long-lasting results in the treatment of hypersplenism in
      cirrhosis.

PMID- 9584460
TI  - [Arterial redistribution of extrahepatic collaterals to the liver under temporary
      balloon occlusion of the proper hepatic artery].
AB  - Three patients with liver metastases receiving transarterial chemotherapy
      underwent embolization of extrahepatic collaterals to the liver under temporary
      balloon occlusion of the proper hepatic artery. Enhancement in the liver and
      tumors was observed at CT arteriography through the right inferior phrenic artery
      and was accentuated under balloon occlusion in all patients. A Cyanoacrylate
      Lipiodol mixture was infused through the right inferior phrenic artery to occlude
      arterial communications with intrahepatic arteries. Better contrast agent
      distribution was obtained in all patients after embolization. It is suggested
      that this procedure can be effective for arterial redistribution against
      extrahepatic collaterals to the liver.

PMID- 9584461
TI  - [Detection of recurrent rectal cancer using helical CT with SmartPrep: a new
      technique for obtaining optimal contrast enhancement].
AB  - Seven patients with suspected recurrent rectal cancer underwent Helical CT using
      SmartPrep. SmartPrep is a software application developed by GE in which the ROI
      is placed at the desired level of the aorta prior to contrast injection. Using a
      low-dose continuous scan, the time density curve was obtained instantly, and the
      optimal timing of scanning was judged from the curve. Four patients who
      demonstrated intense enhancement at the anastomotic site had local recurrence. No
      intense enhancement was observed in these areas on conventional delayed CT. Thus,
      SmartPrep appears to be useful for the accurate diagnosis of recurrent rectal
      cancer.

PMID- 9584463
TI  - [A method for ordering CT examinations on the Intranet].
AB  - We have created a method for ordering CT examinations on the Intranet. Using user
      friendly, free software for Web browsers and server applications, this method is
      easy to operate and inexpensive to install. The database engine, originally
      developed with Perl (Practical Extraction and Report Language), performed
      quickly. Equipped with security and access control functions, the method prevents
      not only illegal access, but also multiple orders placed simultaneously. This
      method enables personal computer users to order CT examinations quickly and with
      assurance.

PMID- 9584462
TI  - [Breath-hold 3D MR urography with 2 ml Gd-DTPA injection].
AB  - Breath-hold gadolinium-enhanced 3D MR urography was performed in five healthy
      volunteers. Enhanced 3D fast gradient-echo with a spectral IR pulse sequence was
      used for depicting MR urography, which was obtained 5-10 minutes after the
      injection of 2 ml of gadopentate dimeglumine (0.013-0.02 mmol/kg). The urinary
      tract was depicted as a high-signal intensity area, and detectability of the non
      dilated urinary tracts was superior to that of heavy T2-weighted images. At the
      same time, comparison between the urinary tract and vascular structure could be
      made using breath-hold contrast-enhanced 3D MR angiography with an additional Gd
      DTPA injection.

PMID- 9584464
TI  - [Importance of AUC of carboplatin in head and neck cancer].
AB  - Combination chemotherapy with Carboplatin (CBDCA) and 5-fluorouracil (5-FU) was
      given to 115 patients with head and neck cancer. The area under the blood
      concentration-time curve (AUC) of CBDCA was calculated by Calvert's formula for
      111 of the 115 patients. A retrospective study was conducted to define the
      relationship between the clinical outcome of the combination chemotherapy and the
      AUC of CBDCA. The overall response rate was 58.4% in the 115 patients. The
      objective response rate for 103 patients with squamous cell carcinoma was 61.9%
      with eight (7.6%) with complete responses (CR) and 57 (54.3%) with partial
      responses. The mean AUC for the administration of 300 mg of CBDCA per m2 was 3.91
      +/- 0.68 mg/ml.min in the patients with squamous cell carcinoma. Although, there
      was no statistically significant relationship between the AUC of CBDCA and
      therapeutic efficacy, all CRs were obtained at an AUC above 3. Thrombocytopenia
      was the major dose-limiting toxicity in this study. The magnitude of
      thrombocytopenia increased significantly with increase in AUC values. Severe
      thrombocytopenia did not seem to occur in the patients with an AUC under 4.5.
      From these results, the AUC was considered helpful for determining the CBDCA dose
      to prevent severe side effects. In respect of both therapeutic efficacy and
      toxicity, AUC values from 3 to 4.5 are recommended for neo-adjuvant chemotherapy
      with CBDCA and 5-FU. Prospective validation is necessary to settle the question
      of whether a higher AUC value within this range can improve the outcome.

PMID- 9584465
TI  - [Obstructive sleep apnea in children with cerebral palsy].
AB  - To determine the etiology of obstructive sleep apnea (OSA) in children with
      cerebral palsy (CP), a survey using a questionnaire was conducted on parents of
      233 CP children (1-5 years old, mean age: 2.7) and on those of 343 control
      children during a routine medical check-up at the age of three. The prevalence of
      habitual snoring and nasal obstruction was 63 and 20% in CP children, which were
      significantly higher than in control children. Sleep apnea episodes and stridor
      were noted in 19.7 and 15.4% of CP children. A screening sleep study was
      performed using Apnomonitor II and a pulseoximeter (Pulsox 5) in 48 CP children
      whose questionnaires revealed habitual snoring and sleep apnea, and it was found
      that 27 and 58% of the children had on apnea-hypopnea index (AHI) of greater than
      5 and a low level of SaO2 (LSaO2) of less than 85%, respectively. When another 10
      CP children visited our hospital for treatment of severe OSA, precise evaluations
      including pharyngeal pressure and fiberscopic examination during sleep as well as
      a sleep study using an inductive prezysmograph (Respigraph) were performed.
      Adenoid and/or tonsillar hypertrophy were noted in only 4 children, and the main
      cause of sleep apnea in the other 6 children was pharyngeal collapse at the
      lingual base. Their OSA was successfully treated by adenotonsillectomy in 2
      children, adenotomy in 2 children, UPPP and lingualplasty in 1 child,
      tracheostomy in 2 children, and nasal CPAP in 1 child. Before treatment of OSA in
      CP children, precise evaluation is recommended in order to perform appropriate
      treatment.

PMID- 9584466
TI  - [Clinicopathological investigations of the dental diseases caused by maxillary
      lesions].
AB  - Clinicopathological investigations of five surgery-requiring dental diseases
      caused by maxillary lesions were conducted. 1) The maxillary lesions were acute
      maxillary sinusitis and a postoperative maxillary cyst. 2) The clinical symptom
      was persistent cheek pain, even though the maxillary lesions were improved and
      there were no lesions in the tooth crown or periodontal tissue. 3) All of the
      teeth with dental diseases caused by maxillary lesions had percussion pain. 4)
      The pathological findings of the dental diseases were ascending pulpitis and
      pulpal necrosis caused by maxillary lesions. 5) When patients complain of
      persistent cheek pain even though maxillary lesions are improved and there are no
      lesions of the tooth crown or periodontal tissue, we should doubt the presence of
      dental diseases caused by maxillary lesions (ascending pulpitis and pulpal
      necrosis).

PMID- 9584467
TI  - [Evaluation of optokinetic afternystagmus (OKAN) induced by cyclo-rotatory
      optokinetic stimulation (C-OKst)].
AB  - It is not known whether the optokinetic afternystagmus (OKAN) can be evoked by
      cyclo-rotatory optokinetic stimulation (C-OKst) or not. Accordingly, this study
      was designed to investigate the problem by using a rotating white dome with
      random dots. Optokinetic nystagmus (OKN) and OKAN in standing upright, supine,
      and prone positions were recorded and analyzed with an infrared-ray CCD camera
      and computed picture analyzer. During stimulation, rotatory OKN showed clearly,
      but there was no slow-rise component. The OKAN was continuously recorded and
      analyzed. The component of this OKAN was found only in the head-horizontal
      direction (yaw axis) in all different head positions. It appeared fairly
      constantly in the prone posture. The velocity storage mechanism (VSM) had to be
      charged by the C-OKst, but the OKAN (1st phase) appeared only in the yaw axis,
      not in the roll axis.

PMID- 9584468
TI  - [Flow cytometric DNA analysis and MR imaging of salivary gland tumors].
AB  - We correlated the histopathology of 32 cases of salivary gland tumors with MR
      imaging and flow cytometric DNA analysis. All malignant tumors were invasive
      and/or had an ill-defined margin. Fifty-seven percent of the pleomorphic adenomas
      were shown as a high signal intensity area on T2 weighted images. Fifty-six
      percent of Warthin tumors were shown as a low or iso signal intensity area on T2
      weighted images associated with the cystic portion. Sixty-seven percent of
      malignant tumors were characterized by DNA aneuploidy and/or a total percentage
      of the S-phase fraction plus the G2 + M fraction higher than 10%. It was less
      than 10% and the Ki-67 positive fraction was higher than 20% in all pleomorphic
      adenomas. The Ki-67 positive fraction was less than 20% in 78% of Warthin tumors.
      The histopathology of all malignant tumors, 86% of the pleomorphic adenomas, and
      89% of Warthin tumors was correctly predicted by the combination of MR images and
      flow cytometry. We suggest that the MR images combined with flow cytometric
      analysis of fine needle aspiration-derived materials is useful in the pre
      operative histopathologic diagnosis of salivary gland tumors.

PMID- 9584469
TI  - [Is a maxillary prosthesis difficult for patients with trismus?].
AB  - Of patients with a postoperative maxillary defect, around 30% are though to have
      trismus to some extent. In these patients, some difficulty in fabricating a
      maxillary prosthesis is expected. In this study, 54 patients with trismus were
      compared with a control group to find some proof of difficulty in making a
      maxillary prosthetics. Fifty-four of trismus less than 20 mm of a mandibular
      stroke were experienced out of 185 patients with maxillary prosthetics between
      October 1984 and October 1992. The trismus was divided into 4 groups of less than
      5 mm (1 case), 5 mm-10 mm (10 cases), 11 mm-15 mm (19 cases), and 16 mm-20 mm (24
      cases). These case were analyzed by in taking an impression failure, average
      weight of the prosthesis, time needed to complete the prosthesis and some special
      form of prosthesis. No apparent differences among the 4 groups or with the
      control group were found. The cause of the difficulty in making a prosthesis for
      such patients with trismus are suggested not to be simply due to the range of
      mouth opening but also to the complexed space formed by the dental defect,
      alveolar bone defect, spreadability of the lip and the cheek, the mandibular
      stroke and the so-called scar bundle of the cheek next to the defect.

PMID- 9584470
TI  - [Usefulness and limitation of crico-pharyngeal myotomy and laryngeal suspension
      after wide resection of the tongue or oropharynx].
AB  - To prevent post-surgical dysphagia in oral or oropharyngeal cancer patients,
      crico-pharyngeal myotomy and laryngeal suspension are recommended; however, its
      indication has been controversial. When it was though that patients would lose
      the mechanisms of laryngeal elevation or mechanisms to produce oropharyngeal
      pressure we opted for crico-pharyngeal myotomy and laryngeal suspension: total or
      subtotal glossectomy with bilateral resection of suprahyoid muscles, and wide
      resection of the oropharynx including the tongue base. In this paper, we report
      the usefulness and limitation of crico-pharyngeal myotomy and laryngeal
      suspension after wide resection of the tongue or oropharynx. PATIENTS AND
      METHODS: From April 1992 to January 1996, 19 patients received circo-pharyngeal
      myotomys and laryngeal suspensions along with their initial operation for oral or
      oropharyngeal cancer. Their ages ranged from 28 to 69 years. Fourteen had tongue
      cancer and 5 had oropharyngeal cancer. We examined the relationship between the
      ability to have an oral diet and the extent of mobile tongue resection, extent of
      tongue base resection, and extent of resection of the lateral wall of the
      oropharynx, reconstruction method, and age. RESULTS: Fifteen of the 19 patients
      (68%) could have an oral diet when they were discharged. The extent of tongue
      base resection (more than 50%) and age (> or = 60) significantly affected post
      surgical aspiration. Two patients who had total glossectomy with total tongue
      base resection could have an oral diet. They were 41 and 51 years old. One 35
      year-old patient who had total glossectomy with wide tongue base resection (80%)
      was able to have the same diet as his family. On the other hand, 4 elderly
      patients (> or = 60) who had wide resection of the tongue base (> or = 50%) could
      not have an oral diet at all. CONCLUSION: A crico-pharyngeal myotomy and a
      laryngeal suspension can contribute to the prevention of post-surgical dysphagia.
      However, if an elderly patient (> or = 60) has had wide tongue base resection (>
      = 50%), he may not be able to have an oral diet. In these cases, we have to opt
      for additional methods, such as total laryngectomy, to prevent aspiration.

PMID- 9584471
TI  - [Immunohistological studies on growth potential of head and neck carcinomas].
AB  - In order to evaluate the growth potential of head and neck carcinomas, the S
      phase cell labeling index (SLI) of biopsied specimens from 106 patients was
      determined immunohistological examination using anti-BrdU monoclonal antibody.
      Expression of epidermal growth factor receptor (EGFR) was also investigated in
      these specimens. The results were statistically compared with clinical findings,
      and the conclusions were as follows: SLI was higher in advanced cases than in
      early cases, and it was higher in patients with lymph node metastasis than in
      those without metastasis. The survival rate showed a strong tendency to be lower
      for patients with higher SLI. No relationship was found between SLI and origin of
      head and neck carcinomas. No relationship was found between SLI and
      differentiation of carcinomas. Expression of EGFR showed no relationship with T
      classification, but the incidence of positive expression of EGFR was higher in
      patients with lymph node metastasis than in those without metastasis. Patients
      positive for EGFR tended to have lower survival rates than EGFR-negative
      patients. The incidence of positive expression of EGFR was statistically higher
      in patients with hypopharyngeal carcinoma than in those with other head and neck
      carcinomas. No relationship was found between the expression of EGFR and
      differentiation of carcinomas. Patients with positive expression of EGFR showed a
      strong tendency to have a higher SLI. SLI and the expression of EGFR may well
      reflect the growth potential of head and neck carcinomas, and it seems very
      likely that they are can be used to evaluate the oncological characteristics to
      predict the out come of each case.

PMID- 9584472
TI  - Successful management of left main bronchial stenosis as a rare complication of
      pericardiectomy.
AB  - We present a rare complication of pericardiectomy and the effective management
      thereof. A 67-year-old female with dyspnea and upper abdominal pain was received
      at our department upon referral. Chest roentgenogram and cardiac catheterization
      preceded a diagnosis of constrictive pericarditis. Pericardiectomy was performed
      subordinate to median sternotomy and left anterolateral thoracotomy. Extubation
      was carried out on day 2 but reintubation was necessitated on the same day as a
      result of progressive dyspnea. Chest roentgenogram revealed an atelectasis of the
      left lung. Fiberoptic bronchoscopy showed left main bronchial stenosis resulting
      from a pulsating external structure. A postoperative computed tomogram
      substantiated the stenotic left main bronchus between the dilated left pulmonary
      artery and the thoracic descending aorta. An expandable metallic stent for the
      treatment of this complication was selected over other invasive procedures. Two
      years of follow-up reveal no complications. Accordingly, an expandable metallic
      stent has demonstrated its effectiveness not only on bronchial stenosis due to
      malignancy or tuberculosis but on benign cases such as this as well.

PMID- 9584473
TI  - Successful surgery for an acute type A aortic dissection following repair of a
      descending thoracic aortic aneurysm.
AB  - Acute type A aortic dissection in the presence of a previously repaired
      atherosclerotic descending thoracic aortic aneurysm is rarely reported. We
      experienced a patient who underwent an ascending aortic replacement with
      reconstruction of the aortic arch 16 months after repair of a descending thoracic
      aortic aneurysm. We succeeded in the redo operation with comprehensive techniques
      involving selective cerebral perfusion, deep hypothermia, early antegrade
      systemic circulation for cerebral protection, and femoro-femoral bypass with
      occlusion of the descending aorta for lower systemic perfusion as well as renal
      perfusion. The patient recovered and is doing well one year after the redo
      operation.

PMID- 9584474
TI  - Aortic valve replacement after previous coronary artery bypass grafting in a
      patient with antiphospholipid syndrome.
AB  - We report a 55-year-old female patient with antiphospholipid syndrome secondary
      to systemic lupus erythematosus. The patient had undergone coronary artery bypass
      grafting for myocardial infarction due to left main trunk stenosis at the age of
      52. Subsequently, she developed aortic insufficiency and underwent aortic valve
      replacement without any hemodynamic or hemostatic problems. Both coronary and
      valve disease should be considered in patients with antiphospholipid syndrome
      secondary to systemic lupus erythematosus.

PMID- 9584475
TI  - [Study on surgical treatment for lung cancer associated with giant bullous
      disease].
AB  - Five patients of primary lung cancer with giant bullous disease underwent surgery
      from April 1985 to December 1995. All patients were male and heavy smokers, and
      the median age was 50 years. The location of the tumor was in the right upper
      lobe in four patients and in the left upper lobe in the other. Three patients
      were treated by lobectomy and two by sleeve lobectomy. Histological examination
      showed large cell carcinoma in four patients and poorly-differentiated
      adenocarcinoma in the other. The pathological stage was I in three. IIIA in one,
      and IV in the other. Two of three in stage I have survived for more than 6 years
      postopertively without recurrence, and the other died of brain metastasis. The
      stage IIIA case and the IV case died 3 years and one year postoperatively,
      respectively. The clinical features of lung cancer associated with giant bullous
      disease was discussed by reviewing 33 patients reported in Japan, including our
      patients. In 13 patients, lung cancer and bullous disease were diagnosed
      simultaneously (group A), and in 20 patients, bullous disease were diagnosed
      prior to the appearance of an abnormal shadow due to lung cancer (group B). The
      patients in group B had a tendency to be diagnosed at an earlier stage of lung
      cancer than the patients in group A. In the patients of stage I, the 5-year
      survival rate was 78.6%, however, in the patients of more than stage IIIA, 3-year
      survival rate was 26.5% and the 5-year survival rate was 0%. Significant
      differences in the survival curves were demonstrated between the cases with stage
      I and the cases with more than stage IIIA. In conclusion, in order to improve the
      prognosis of lung cancer with giant bullous disease, it is considered to be
      important to detect giant bulla prior to lung cancer, and when a case of bullous
      disease is found, periodical follow-up must be done to find early stage lung
      cancer.

PMID- 9584476
TI  - [Preoperative autologous donation of blood in cardiac surgery--age related
      factors].
AB  - We have studied influence of the age related factors on preoperative autologous
      donation (PAD) of blood in cardic surgery. PAD was undertaken in 246 cases of
      elective cardiac surgery by means of simple or leap-frog method, starting at
      approximately 4.5 weeks before operation. It provided 1726 ml of autologous blood
      storage on the average. Sorting the patients into three groups with age, leading
      surgical procedures were as follows: closure of the atrial septal defect (ASD) in
      teen 30s (group L, n = 51), aortic valve replacement (AVR) or mitral valve
      replacement (MVR) in 40s-50s (group M, n = 83) and 60s and over (group H, n =
      112). Coronary artery bypass grafting (CABG) was more common in group H. Percent
      freedom from allogeneic blood transfusion was 82.3% in group L, 80.7% in group M
      and 61.6% in group H, respectively (p < 0.05; L, M vs. H), donated blood volume
      in group H was significantly less than that of group M (p < 0.05, M: 1987 +/- 63,
      H: 1610 +/- 60 ml), because blood volume and hemoglobin level before donation
      tended to be less in group H. Each group did not differ in blood loss during and
      after operation, which showed a significant positive correlation with operation
      time and cardiopulmonary bypass (CPB) time. Comparing factors in ASD, CPB time
      was relatively long, and postoperative blood loss was significantly larger in
      group H (p < 0.05; L: 432 +/- 71 ml, M: 369 +/- 34 ml, H: 754 +/- 124 ml). This
      finding suggests that the secondary lesions in age ASD cases adversely affected
      hemostasis. As to AVR, MVR and CABG, there were no differences in these factors
      but donated blood volume among three groups. We conclude that elderly patient
      (60s and over) tends to necessitate allogeneic blood transfusion in cardiac
      surgery because of the insufficient PAD. Earlier commencement of PAD or
      concomitant application of erythropoietin will improve this situation.

PMID- 9584477
TI  - [The surgical treatment for acute aortic dissection--a retrospective study from
      the statistics of affiliated hospitals of a medical school].
AB  - A retrospective study was conducted for the surgical treatment on acute aortic
      dissection among the cardiovascular services of 5 affiliated hospital of medical
      school. The total of 74 cases were operated for the last 5 years period from
      Jan., 1991 to Dec., 1995, in which 64 cases were classified as Type A and 10 for
      Type B. The average age for Type A was 58.4 years old and 10% of patients were
      consisted of Marfan syndrome. The most frequent complications associated with
      dissection was aortic regurgitation (37.5%), followed by cardiac tamponade
      (23.4%). The surgeries were undertaken in less than 24 hours from the onset of
      symptom in 45.3% of patients. The localization of initial tear as was proved by
      intraoperative finding was at ascending aorta in 64.0%, whereas it was found at
      aortic arch in 21.8% of patients. The most frequent application of operative
      procedure was simultaneous graft replacement of ascending aorta and aortic arch
      (68.7%) with the use of profound hypothermia and antegrade selective cerebral
      perfusion (85.4%). The overall mortality rate was 25.0%, however when compared as
      ascending only vs ascending + arch replacement, the later group demonstrated
      higher mortality rate (16.6% vs 28.9%). The majority of surgical indication for
      Type B was hemorrhage from the dissection and 20.0% of mortality was recorded in
      this group of patients.

PMID- 9584478
TI  - [Evaluation of hilar pulmonary vessels using magnetic resonance angiography
      (MRA)].
AB  - To evaluate the usefulness of magnetic resonance angiography (MRA) in pulmonary
      and mediastinal diseases, 24 cases (15 lung cancers, 2 metastatic lung tumors and
      7 other diseases) were studied with the 3D FLASH (TE = 3 msec.) method. In
      resected cases, MRA images were compared with intraoperative findings. Twenty of
      24 cases were consistent with intraoperative findings. In 4 resected cases in
      which the findings were inconsistent, pulmonary angiography (PAG) findings were
      similar to those of MRA. From these results, MRA is considered an effective and
      non-invasive method for evaluation of pulmonary vessels.

PMID- 9584479
TI  - [Magnesium and calcium changes in serum and atrial muscle caused by open heart
      surgery and the effect of preoperative oral magnesium administration].
AB  - The study was undertaken to compare magnesium and calcium serum concentration
      levels and magnesium and calcium atrial muscle content of between the non
      magnesium group (20 patients) and the magnesium group (11 patients) in the
      perioperative period of open heart surgery. In addition, the incidence of
      arrhythmias was compared between the two groups. Late ventricular potentials and
      postoperative ventricular arrhythmias were evaluated in both groups. The patients
      of the magnesium group were administered a daily oral intake of 3.0 g of
      magnesium oxide for ten days before operation. In both groups, serum
      concentration of magnesium decreased abruptly due to hemodilution after the
      operation and began increasing gradually from 24 hours after the operation.
      However, in the non-magnesium group the concentration decreased below the normal
      range in the 24 hour period after the operation and elevated to above the
      preoperative value from the third to fifth postoperative days. In the magnesium
      group serum concentration of magnesium was higher during the 24 hours after the
      operation and lower from the third to fifth postoperative days than the non
      magnesium group. Thus, the fluctuation was smaller in the magnesium group than
      the non-magnesium group. Serum concentration of calcium also decreased abruptly
      after the operation and gradually increased in the postoperative days in both
      groups. However, the level was always higher in the magnesium group than the non
      magnesium group. The concentration ratio of serum calcium to magnesium was
      relatively unchanged postoperatively in the magnesium group, whereas it decreased
      significantly from the second to seventh postoperative days in the non-magnesium
      group. Magnesium and calcium contents in the atrial muscle were measured before
      and after cardiopulmonary bypass. Before bypass, magnesium and calcium contents
      were higher in the magnesium group than the non-magnesium group. However, in the
      non-magnesium group the calcium content increased significantly after bypass
      compared to pre-bypass levels, whereas it was unchanged in the magnesium group.
      Ventricular arrhythmias severer than grade 3 were found in 4 cases in the non
      magnesium group. On the other hand, no ventricular arrhythmias severer than grade
      3 were found in the magnesium group. As to the incidence of supraventricular
      arrhythmias, no difference was demonstrated between both groups. The appearance
      of late ventricular potentials on signal averaged electrocardiograms was found
      variable and often transient, and no association was found between the appearance
      of late ventricular potentials and the incidence of ventricular arrhythmias.
      Smaller fluctuations of magnesium and calcium concentrations in serum as well as
      in the atrial muscle were observed in the postoperative days in the magnesium
      group. Magnesium and calcium ratio also showed smaller fluctuations in the
      postoperative days in the magnesium group. In conclusion, these factors, along
      with suppression of calcium influx in the cardiac muscle, appeared to serve to
      reduce the incidence of ventricular arrhythmias in the magnesium group.

PMID- 9584481
TI  - [Resection of a pulmonary infarction presenting as a mass shadow on chest X-ray-
      case report].
AB  - Recently the incidence of pulmonary infarction has increased in Japan. The
      patient was a 67-year-old male who was examined by a local physician for bloody
      sputum and a cough. A chest X-ray showed a 5-cm mass shadow in the lower left
      lung area. Bronchofiberscopy and percutaneous needle biopsy were performed, but
      they did not permit a definite diagnosis, and since the patient had a 13-year
      history of penile cancer (squamous cell carcinoma), and metastasis or even
      primary lung cancer could not be completely ruled out, an open chest biopsy was
      performed. The postoperative histopathological examination allowed a diagnosis of
      hemorrhagic pulmonary infarction. We report a case of pulmonary infarction
      resection that was difficult to diagnose preoperatively.

PMID- 9584480
TI  - [Removal of retained transvenous pacemaker electrodes under cardiopulmonary
      bypass].
AB  - A case of breakage and removal of a retained transvenous pacemaker electrode is
      described. A 22-year-old woman with complete A-V block underwent implantation of
      a transvenous pacemaker system on the left anterior chest wall in 1989. Three
      years later, a new generator was implanted on the right chest wall because of
      local infection of the pacemaker pockets. The old electrodes could not be removed
      and were left in place. Beginning in 1995, the patient complained of anterior
      chest pain. A chest roentgenogram revealed that one of the pacemaker electrodes
      had broken at the right costoclavicular ligament and a fragment was floating in
      the superior vena vava. The retained electrodes were removed under tot
      cardiopulmonary bypass. These electrodes had become firmly encased with fibrous
      tissue within the right ventricle and atrium, but they were easily removed under
      direct vision duting complete cardiac arrest. The postoperative course was
      uneventful and the patients had no further complaint.

PMID- 9584482
TI  - [Surgical treatment with infarction exclusion technique and postoperative
      percutaneous cardiopulmonary support for a patient with ventricular septal
      perforation--a case report].
AB  - A 76-year-old woman was referred to our hospital because of postinfarction
      ventricular septal perforation (VSP). VSP occurred twelve days after acute
      myocardial infarction and resulted in interventricular shunt with Qp/Qs of 4.8.
      Because she suffered from pulmonary edema and oligouria, she underwent emergent
      surgical treatment after application of the intraaortic balloon pump. The
      infarction involved whole of right ventricle and the infero-posterior wall of
      left ventricle, and the location of the perforation was infero-septum with the
      size of 10 x 6 mm. A bovine pericardial patch was tailored in a triangular shape
      of approximately 7 x 7 x 5 cm. The base of the patch was sutured to the fibrous
      annulus of the mitral valve and medial margin of the patch was sewn to healthy
      septal endocardium. And the lateral side of the patch was sutured to the
      posterior wall of the left ventricle. Because of difficulty in weaning of the
      cardiopulmonary bypass, a percutaneous cardiopulmonary support system (PCPS) was
      inserted via femoral artery and vein with a flow support of 2.0 L/min. After 4
      days support of PCPS, improvement of right ventricular function was detected by
      echocardiogram and PCPS was removed. While PCPS support, low dose heparin to
      maintain ACT level around 150 seconds was continuously administered. Any
      complication including bleeding and thrombosis was not remarkable. The patient
      was discharged on the 53th postoperative day, and is now doing well.

PMID- 9584483
TI  - [Intrathoracic vagal nerve schwannoma preoperative diagnosis is correct because
      of clinical and characteristic CT findings--a case report and review of the
      literature].
AB  - A 60-year-old man was operated with the clinical diagnosis of intrathoracic vagal
      nerve schwannoma because of characteristic CT findings and no symptom of
      neurofibromatosis. Thoracoscopic surgery was performed and it was confirmed
      pathologically. Intrathoracic vagal nerve tumor is rare, so preoperative
      diagnosis seems to be difficult. We review the intrathoracic vagal nerve tumors
      reported in Japan (52 cases of schwannoma and 9 cases of neurofibroma), and
      analyzed the tumor location, furthermore, the relationship of neurofibromatosis
      and schwannoma and neurofibroma on vagal nerve tumor.

PMID- 9584484
TI  - [Surgical treatment for lung cancer invading thoracic aorta].
AB  - We experienced three surgical cases of lung cancer invading thoracic aorta, and
      discussed some problems in order to improve the surgical outcome. In the first
      case, the patient had a ruptured descending aortic aneurysm into a tumor of left
      lung. Following urgent graft replacement of descending aorta, left pneumonectomy
      was carried out, but the patient died of bone marrow dissemination which was
      probably caused by aspiration of the tumor cells on cardiopulmonary bypass. In
      the second case, the patient underwent resection of the left upper lobectomy
      combined with resections of the left subclavian artery and distal aortic arch,
      but died of perforation of aortic arch due to vascular injury by cross clamp. In
      the third case, an operation was successfully performed for lung cancer invading
      the aortic arch. Left upper lobectomy with associated resection of aortic arch,
      left subclavian and common carotid arteries was performed. Both arteries were
      replaced with a Gelseal Graft.

PMID- 9584485
TI  - [Prevention and treatment of osteoporosis].

PMID- 9584486
TI  - [Recent progress in the study on apoptosis].

PMID- 9584487
TI  - [Recent view in osteoporosis].

PMID- 9584488
TI  - [Implication of near-death experience for the elderly in terminal care].
AB  - Near-death experience (NDE) was studied in a series of 48 consecutive patients
      who were admitted to hospital in a deep coma (level III on the III-3 coma scale)
      due to cardiac arrest, pulmonary failure, cerebrovascular accident, and/or other
      life-threatening disease. When the patients recovered from coma without
      complications such as aphasia, dementia or mental disturbance, they were
      interviewed by the same physician following the same protocol consisting of 25
      questions about their experience during the period of deep coma. Of 48 patients
      interviewed, 14 (37%) had a vivid and undeniably personal experience during their
      unconscious state. Factors attributable to the NDE were assessed by the following
      three methods. First, the frequency and odds ratio were examined in terms of
      gender, age, underlying disease, occupation, religion, education, site of
      accident, duration of comatose state, drugs and treatment for resuscitation, and
      drugs being taken at the time of interview. There were no specific factors
      significantly related to the NDE. Next, background factors were compared between
      the NDE positive and negative groups to detect a particular factor related to the
      NDE. However, there were no factors that showed significant frequency in the NDE
      positive group. Finally, discriminatory analysis was performed to detect
      discriminatory factors in the occurrence of NDE by selecting NDE as an objective
      variable and background factors as explanatory variables. However, the
      discriminatory equation gained was not significant. Thus, there were no
      background factors that could explain the occurrence of NDE. Among the NDE
      reported, there were such elements as flying in a dark void space with dim light
      ahead, encountering dead relatives or friends, standing at the boundary of brook,
      river or pond, and returning to the world in response to a voice calling from
      behind. These elements are common to those reported by investigators abroad,
      except for the lack of a tunnel experience. As for the influence of the NDE on
      life subsequent to the experience, the majority of patients who had had a NDE
      stated that they became more sincere to towards every aspect of life and held
      spiritual values in high esteem than before. This was quite a contrast to the
      attitudes in the non-NDE patients who looked upon the comatose episode as arising
      from an underlying disease and considered it a health problem only. Most of the
      NDE patients considered that death was neither fearful nor difficult, but calm
      and peaceful if it occurs in a manner similar to that in their NDE. From this
      study, a picture can be down of the dying process, based on empirical
      information, it can also be seen that a NDE causes the individual to develop a
      sincere introspective depth. It is possible that these findings may be applicable
      to elderly patients in terminal care.

PMID- 9584489
TI  - [Blood pressure and diastolic function in the elderly].
AB  - To evaluate the relation between blood pressure and diastolic function in the
      elderly, 28 apparently healthy volunteers underwent blood pressure measurements,
      echocardiographic examinations, and radionuclide angiography acquired in list
      mode. Casual blood pressure did not correlate with diastolic indices measured
      either by echocardiography or by a radionuclide method, except for peak filling
      rate during atrial contraction assessed by radionuclide angiography (r = 0.39, p
      < 0.05). Ambulatory blood pressure monitoring revealed significant correlations
      between peak filling rate during atrial contraction assessed by radionuclide
      angiography and blood pressure measured over 24 hours, while awake and during
      sleep. The time to peak filling rate and the velocity of early diastolic filling
      were found to correlate with blood pressure, but the best correlation was between
      blood pressure during sleep and peak filling rate during atrial contraction (r =
      0.53, p < 0.005). These results show a direct relation between blood pressure and
      diastolic function in the elderly, which is stronger during sleep than during
      wakefulness.

PMID- 9584490
TI  - [Prevalence of affective disorders on the basis of DSM-III among the elderly in a
      rural community in Japan].
AB  - The prevalence rates of affective disorders among the elderly in a rural
      community according to the criteria of the third edition of Diagnostic and
      Statistical Manual of Mental Disorders were investigated. The survey used a two
      phase method which combined a self-administered depression scale and diagnostic
      interviews by psychiatrists. The subjects were all 766 persons aged 65 years or
      older in a rural village in Japan. In the first phase, 698 persons completed a
      self-administered scale, the Center for Epidemiologic Studies Depression scale
      (CES-D). In the second phase, 83 persons scoring 12 points or more on the CES-D
      and an additional 8 persons who, for unknown reason, did not respond to the CES-D
      were assessed by psychiatrists using a modified version of the Diagnostic
      Interview Schedule. The subjects' physical health and life events, the presence
      of dementia, and other factors were taken into account when diagnoses were made.
      The point prevalence rates of depression without dementia as a comorbid condition
      by category were as follows: major depression, 0.5%; dysthymic disorder, 0.3%;
      and atypical depression, 0.4%. The point prevalence rates of depression with
      dementia as a comorbid condition were as follows: major depression, 0.7%;
      dysthymic disorder, 0.4%; and atypical depression, 0.4%. Major depression was
      more prevalent in women than in men and was more prevalent in persons aged 75
      years of older than in younger subjects.

PMID- 9584491
TI  - [Hemodynamics of asymptomatic brain infarction determined by Doppler sonography].
AB  - We compared the usefulness of two methods for diagnosing asymptomatic brain
      infarction: an ultrasonic quantitative flow measurement system (QFM) and a
      transcranial Doppler arteriography (TCDA). A total of 137 patients (73 men and 64
      women) who underwent magnetic resonance imaging of the brain, QFM, and TCDA were
      enrolled. Their ages ranged from 41 to 83 years (mean age, 63 years). The
      patients were divided into 3 groups: 45 without cerebrovascular disease (Group
      N); 40 with asymptomatic brain infarction (Group AS); and 52 with lacunar
      infarction (Group LI). The mean blood flow in the common carotid artery (CCA-BF)
      was measured by QFM. The mean blood velocity and Fourier pulsatility index in the
      middle cerebral artery (MCA-BV, MCA-PI) were measured by TCDA. In Group N, 28
      patients were examined twice at a mean interval of 2 years; 19 remained without
      asymptomatic brain infarction (Group N1), and asymptomatic brain infarction
      developed in the remaining 9 (Group N2). The 3 groups differed significantly in
      MCA-PI (N < AS < LI), but not in CCA-BF or in MCA-BV. The MCA-PI in Group N2 was
      higher than that in Group N1. These results indicate that the Fourier pulsatility
      index determined by TCDA may be useful for detecting the onset of asymptomatic
      brain infarction.

PMID- 9584492
TI  - [A case of mild-type myotonic dystrophy with dementia and severe arteriosclerosis
      obliterans].
AB  - A 70-year-old man, with mild-type myotonic dystrophy (MyD) diagnosed by molecular
      genetic analysis when he was 68 years old, complained of worsening intermittent
      claudication during the past 2 years. Doppler examination revealed severe
      stenosis and obstruction in his leg arteries, which we diagnosed as
      arteriosclerosis obliterans (ASO). We then found him to be suffering from
      dementia, which was confirmed by dementia scale tests (Mini Mental State, 20/30;
      Hasegawas' Dementia Scale-Revision, 15/30). Even in mild-type MyD, as MyD is one
      of the progeria syndromes, the abnormal genes of MyD may accelerate the aging
      processes.

PMID- 9584493
TI  - [Malignant syndrome associated with disseminated intravascular coagulation and a
      high level of amylase in serum, followed by diabetic coma in an elderly patient
      with Parkinson's disease during L-dopa therapy].
AB  - A 66-year-old woman with a 7-year history of Parkinsons' disease was admitted to
      our hospital because of a high fever and disturbance of consciousness. She had
      been treated with levodopa/benserazide hydrochloride and trihexyphenidyl
      hydrochloride until admission. On admission, the patient was comatose, her
      temperature was 40.5 degrees C, her blood pressure was 54/-mmHg, and her pulse
      rate was 130 beats/min. Laboratory tests showed leukocytosis, a high level of
      creatine kinase in serum and evidence of hyperosmolar non-ketotic diabetic coma
      (blood glucose, 1,080 mg/dl) and of disseminated intravascular coagulation (DIC).
      A continuous insulin infusion, antibiotics, nafamostat mesilate, and urinastatin
      were given, after which the DIC, hyperglycemia, and the level of consciousness
      were improved. However, levels of creatine kinase, myoglobin, transaminase, and
      amylase in serum continued to increase, and multiple organ failure was suspected.
      Furthermore, she became less responsive, diaphoretic, and tremulous; fever and
      mild rigidity developed. The peak creatine kinase and myoglobin were 11,095 U/l
      and 12,520 ng/ml, respectively. A diagnosis of malignant syndrome was made, and
      treatment with levodopa/carbidopa and dantrolene was begun. Within several days,
      the clinical and laboratory findings improved. We report here a rare case of
      malignant syndrome associated with DIC followed by diabetic coma in an elderly
      patient with Parkinsons' disease during L-dopa therapy. Timely diagnosis and
      treatment of malignant syndrome are important in the management of elderly
      patients with Parkinsons' disease, because DIC and multiple organ failure may
      occur in the early stages of malignant syndrome.

PMID- 9584494
TI  - Dietary nitrates, nitrites, and N-nitroso compounds and cancer risk: a review of
      the epidemiologic evidence.
AB  - Experimental animal studies have shown N-nitroso compounds (NOC) to be potent
      carcinogens. Epidemiologic evidence of the carcinogenic potential of dietary NOC
      and precursor nitrates and nitrites in humans remains inconclusive with regard to
      the risk of stomach, brain, esophageal, and nasopharyngeal cancers. Inadequate
      available data could obscure a small to moderate effect of NOC.

PMID- 9584495
TI  - The obesity epidemic is a worldwide phenomenon.
AB  - Obesity is not just a disease of developed nations. Obesity levels in some lower
      income and transitional countries are as high as or higher than those reported
      for the United States and other developed countries, and those levels are
      increasing rapidly. Shifts in diet and activity are consistent with these
      changes, but little systematic work has been done to understand all the factors
      contributing to these high levels. The goal of this review is to provide an
      understanding of the patterns and trends of obesity around the world and some of
      the major forces affecting these trends. Several nationally representative and
      nationwide surveys are discussed.

PMID- 9584496
TI  - The State of the World's Children 1998: a UNICEF report. Malnutrition: causes,
      consequences, and solutions.

PMID- 9584497
TI  - Calcium requirements of breast-feeding mothers.
AB  - A randomized, placebo-controlled calcium supplementation study has investigated
      the benefits of increased calcium intake during 6 months of full breast-feeding
      and during the weaning period for lactating women with a dietary calcium intake
      below 800 mg/day, compared with nonlactating women who had recently given birth.
      The calcium supplement of 1000 mg/day had no impact on breast milk calcium
      concentration or on lactation-associated bone mineral changes in the lumbar
      spine, radius, or total body. Calcium supplementation produced a modest increase
      in spine bone mineral density in both lactating and nonlactating women, but the
      potential significance of this effect is unclear. The results of this study
      support and extend the findings from three previous supplementation studies and
      suggest that women do not need to consume extra calcium during breast-feeding.

PMID- 9584498
TI  - Broccoli sprouts in cancer prevention.
AB  - Recent research has aimed to identify specific phytochemicals in Brassica
      vegetables, such as sulforaphane in broccoli, that may confer protection against
      cancer. Clinical, dietary, and policy implications are discussed.

PMID- 9584499
TI  - International perspective: basis, need, and application of recommended dietary
      allowances.
AB  - The RDAs emerged in World War II to thwart existing nutrient deficiencies. The
      RDAs are estimates of need based on the data available. There has been remarkably
      little change in RDA values. The ongoing revision of the RDAs will introduce new
      terminology and attempt to recommend values that not only ensure the prevention
      of nutrient deficiency but that would thwart the more prevalent chronic
      degenerative diseases as well and recommend upper safe limits for RDA nutrients.
      The overall goal is to provide estimates of dietary allowances that are intended
      to avoid preventable illness, including freedom from outright clinical deficiency
      of truly essential nutrients.

PMID- 9584500
TI  - Process and development of dietary reference intakes: basis, need, and
      application of recommended dietary allowances.

PMID- 9584501
TI  - Current status of recommended dietary allowances in Southeast Asia: a regional
      overview.

PMID- 9584502
TI  - Indonesian recommended dietary allowance.

PMID- 9584503
TI  - Philippine recommended dietary allowances: recent developments and future plans.

PMID- 9584504
TI  - Development of Vietnamese recommended dietary allowances and their use for the
      National Plan of Action for Nutrition.

PMID- 9584505
TI  - Overview of key nutrients: energy and macronutrient aspects.

PMID- 9584506
TI  - Overview of key nutrients: micronutrient aspects.
AB  - Micronutrients are the key to optimal macronutrient metabolism because of their
      essential role in metabolism. Invariably, metabolic steps require the concomitant
      involvement of one or more vitamins and minerals. Chronic degenerative disease
      etiology and rate of pathogenesis are intimately associated with micronutrient
      imbalances. Although precise mechanisms remain to be identified, antioxidant
      status is critical in atherosclerosis and cancer pathogenesis. While elucidating
      estimates and establishing "singular" values by sex and age for parameters such
      as estimated average requirements, RDA, and RDI, it is imperative to arrive at
      these estimates in the light of their interdependent role in metabolism.

PMID- 9584508
TI  - Recommended dietary allowances: the industry perspective.

PMID- 9584507
TI  - Recommended dietary allowances: regulatory perspectives.

PMID- 9584509
TI  - Recommended dietary allowances: a nutrition practitioner's perspective.

PMID- 9584510
TI  - Harmonization of recommended dietary allowances: implications and approach.

PMID- 9584511
TI  - Fiber type composition of abdominal muscles in Japanese macaques (Macaca
      fuscata).
AB  - The muscle fiber composition and cross-sectional area of muscle fiber types were
      investigated histochemically in the abdominal muscles (rectus abdominis muscle,
      obliquus externus abdominis muscle, obliquus internus abdominis muscle and
      transversus abdominis muscle) of three Japanese macaques (Macaca fuscata). Muscle
      fibers were classified into three fiber types (Type I, II A and II B) by myosin
      ATPase activity and succinate dehydrogenase activity. Each abdominal muscle in
      Japanese macaques contained high proportion of Type II B fibers and there were no
      large differences in the fiber type composition between the abdominal muscles.
      The range of mean fiber type percent was 26-32% Type I, 21-22% Type II A, and 46
      52% Type II B fibers. Thus, based on the histochemical fiber type composition,
      the separate abdominal muscles appear to have a similar functional capacity. The
      cross-sectional area was larger for Type II than for Type I fibers, and the areas
      were similar in Type II A and Type II B fibers in each muscle. The rectus
      abdominis showed larger fibers of each type compared to the lateral abdominal
      muscles. The high proportion of Type II B fibers and large fiber size for Type II
      B fibers suggest that the abdominal muscles of Japanese macaques have properties
      similar to the propulsive and locomotory muscles in the limbs.

PMID- 9584512
TI  - Mitochondrial fixation for the detection of cytochrome oxidase activity using
      microwave irradiation.
AB  - We examined cell fixation with microwave irradiation (MWI) used in cytochemistry.
      MWI was applied to blocks of about 1 mm3 of mouse parotid glands at 500 W for
      about 5 sec in a fixative at 37 degrees C. The activities of endogenous
      peroxidase and mitochondrial cytochrome oxidase were demonstrated by using the
      DAB method with 3,3'-diaminobenzidine (DAB) and 0.01% H2O2. Under electron
      microscopy, peroxidase activity was localized in the nuclear envelope,
      endoplasmic reticulum and secretory granules. However, mitochondria cytochrome
      oxidase activity seemed to be rather weak against the MWI at 37 degrees C.
      Moreover, suspension of isolated hamster liver mitochondria was fixed by MWI and
      also demonstrated cytochrome oxidase activity by using the cytochemical methods
      with DAB, cytochrome c, catalase and sucrose. Such mitochondrial fractions were
      subjected to 6-second MWI given 10 or 18 times with an interval of 10 seconds
      with and without a chilled water bath. The final temperature of each fixative was
      kept at about 10 degrees C or rose to about 37 and 55 degrees C. When we took
      care to keep the temperature below 10 degrees C, the DAB reaction products
      accumulated in the mitochondrial intermembrane-intracristal space. No
      mitochondrial deposits were observed when the temperatures of the fixatives rose
      to 37 and 55 degrees C. These results indicated that peroxidase was very
      resistant to the heat with MWI fixation. Cytochrome oxidase is sensitive to the
      heat with MWI, so, a chilled water bath had to be used.

PMID- 9584513
TI  - Cellular characterization of the 91kDa-ectopic ascitic antigen sharing
      antigenicity with MRP8 in the human placenta as revealed by immunoelectron
      microscopical colloidal-gold techniques.
AB  - Cellular characterization of the 91kDa-ectopic ascitic protein that exhibits
      pregnancy-associated and tumour-related dynamics has been examined in the human
      placenta using an electron microscopic immunocolloidal-gold technique. This
      protein was initially isolated from the ascitic fluids of a patient suffered from
      ovarian and uterine cancers with mixed mesodermal tumours, and determined to be
      sharing antigenicity with the 28kDa-oncodevelopmental protein and a calcium
      binding protein; MRP8/CFA, respectively. Placentas obtained were divided into
      three groups by their gestational periods. Small chorionic villous tissues were
      embedded in Lowicryl K4M resin or Epon 812 resin. Specific and higher labelings
      by gold-particles were obtained in sections of Lowicryl resin and, then,
      recognized in mesenchyme-derived cells and/or myeloid lineages; such as placental
      tissue macrophages (Hofbauer cells), fibroblasts, foetal myelomonocytic cells
      including endothelial cells, etc., in the first and second trimesters. So far,
      the pattern of antigenic appearances changed depending on the stage of gestation.
      On the other hand, 91kDa-protein was also determined in the syncytiotrophoblast,
      but not in cytotrophoblasts at whenever been examined. It is assumed that the
      antigenic expression in syncytiotrophoblasts might be reflected to be absorbed or
      incorporated from those of foetal or maternal origins, and the antibody used in
      this study should be sensitive to the antigenic epitope derived from those of
      myeloid lineages. In the light of these results, hypotheses concerning mechanisms
      of both transplacental permeability of substances by the placental barrier and
      cell/tissue differentiation by calcium-binding (and/or -depending) proteins such
      as 91kDa-protein, MRP8, etc.; presumable the S-100 protein family, are discussed
      further.

PMID- 9584514
TI  - Relationship of substance P- and CGRP-immunoreactive central endings of the
      primary afferent neurons to GABAergic interneurons in the guinea pig substantia
      gelatinosa.
AB  - The synaptic relationships between primary afferent central endings containing
      substance P (SP) and calcitonin gene-related peptide (CGRP) and GABAergic
      interneurons in the guinea pig substantia gelatinosa of the lumbar spinal dorsal
      horn were studied. The pre-embedding PAP method was used for detection of GABA
      and the post-embedding double immunogold labeling method for SP and CGRP
      detection. Immunogold particles specific for SP and CGRP were mainly localized
      separately or together in large synaptic vesicles devoid of dense cores. SP and
      CGRP immunoreactivity was separate or co-localized in small roundish, slender,
      sinuous or large scalloped (fan-like) terminals with closely packed round
      agranular synaptic vesicles of various sizes and few large dense core vesicles
      and mitochondria, which are thought to be capsaicin-sensitive primary afferent
      terminals. These SP- and CGRP-immunoreactive boutons make presynaptic or
      symmetric contacts with GABAergic dendrites and soma. These findings suggest that
      the central endings of nociceptive primary afferents transmit pain stimuli to
      intrinsic inhibitory interneurons, thereby modulating nociceptive information via
      a postsynaptic circuit.

PMID- 9584515
TI  - Crown structure of the maxillary molars in the Japanese shrew mole, Urotrichus
      talpoides (Insectivora, Talpidae).
AB  - The maxillary first and second molars (M1 and M2) in the Japanese shrew mole,
      Urotrichus talpoides, were investigated using an odontometrical approach. The
      mesiodistal crown diameter was larger in M1 than in M2, while the buccolingual
      diameter of M1 was nearly equal to that of M2. M2 was more compressed
      mesiodistally than M1. M1 had a large distal triangle on the stylar shelf. The
      mesial triangle of M2 was slightly larger than the distal triangle. Despite being
      smaller than M1, M2 was less variable than M1 in terms of size. The distal
      triangle of M1 and the mesial triangle of M2 were well developed, and thus this
      area, which corresponds to the inflection point of the maxillary dental arch, was
      most likely the center of an occlusal function.

PMID- 9584516
TI  - Arteries and veins behind the thoracic vertebrae with special reference to the
      cutaneous blood supply.
AB  - One thousand and thirty eight dorsal cutaneous vessels, which emerged onto the
      superficial fascia behind the thoracic vertebrae, were examined with regard to
      the point at which they perforated the fascia, their diameters, intermuscular
      courses and origins. Large vessels (more than 1 mm in diameter) were mainly
      distributed at the T1-T4 level. The intermuscular courses could be classified
      into three groups: a descending scapular course arising from the transverse
      cervical vessels (4.0%), a nerve-accompanying vertebral course (68.6%) and a deep
      vertebral course arising from other origins (27.4%). Vessels with a nerve
      accompanying course ran through the middle sized (3-4 vertebral segments long)
      semispinalis muscle slips and descended over 1-2 vertebral segments. Vessels with
      a deep vertebral course, including the posterior external vertebral venous
      plexus, were located around the rotatores muscle. Vessels with a deep vertebral
      course as well as those following a nerve-accompanying course frequently emerged
      onto the fascia with a nerve since the former merged into the nerve-accompanying
      vessels immediately before perforating the fascia. The potential clinical
      applications of these results are discussed.

PMID- 9584517
TI  - Effect of immobilization on the ultrastructure of the golden hamster parathyroid
      gland.
AB  - To investigate the morphological changes of the parathyroid gland of the
      immobilized hamsters, we studied the ultrastructure of the parathyroid gland of
      golden hamsters kept in special small cage (Ballman cage II). All hamsters of the
      control group were kept in one ordinary cage. Each hamster of the isolated group
      was kept in ordinary cage individually. Each hamster of the immobilized group was
      kept in Ballman cage II individually. All hamsters were kept for 5 days. On the
      first and fifth day of the experiment, bone mineral content (BMC) and bone
      mineral density (BMD) of whole body were measured by dual energy X-ray
      absorptiometry (DXA). In the control and isolated groups, BMD of the fifth day
      was significantly increased as compared to that of the first day. In the
      immobilized group BMC and body weight were significantly decreased. There was no
      significant difference among 3 groups concerning the mean serum calcium level.
      Volume density of the cell organelles and inclusions was estimated and compared
      among 3 groups. Volume density of the lysosomes and large vacuolar bodies of the
      isolated and immobilized groups was significantly higher than that of the control
      group. Much more lipid droplets were observed in the immobilized group than the
      control and isolated groups. No particular differences were observed as to the
      Golgi complex in the isolated and the immobilized groups compared to the control
      group. These findings suggest that the cellular activity of the parathyroid gland
      is suppressed with immobilization.

PMID- 9584518
TI  - Morphometric and allometric study of the mouse exocrine pancreas growth during
      the postnatal life.
AB  - Postnatal mouse pancreas growth was submitted to allometric analysis by the Wald
      nonparametric method, modified by Bartlett. The body and gland mass were obtained
      and the total cell number and the absolute compartmental volumes of acini, ducts
      and stroma were evaluated by morphometric methods. The allometric coefficients
      were calculated for the growths between the following parameters: a) pancreatic
      mass and body mass; b) acinar compartmental volume and body mass; c) ductal
      compartmental volume and body mass; d) stroma volume and body mass; e) total cell
      number and body mass; and f) acinar volume and stroma volume. The results of
      these analysis showed that the pancreatic mass, total cell number and stroma
      volume exhibited statistically significant allometric growths with a monophasic
      pattern and allometric coefficients of 1.56, 1.27 and 1.29, respectively, for the
      periods of 2 to 70, 2 to 28 and 2 to 70 days of age; while the growth of
      compartmental acinar volume in relation to body mass and compartmental stroma
      volume was biphasic. In the first case, the 1st phase occurred between 2 to 14
      days (K = 1.09) and the 2nd phase between 14 to 70 days (K = 1.44) and in the
      second case, the 1st and 2nd phases occurred, respectively, between 2 to 28 days
      (K = 1.31) and 28 to 70 days (K = 0.79) of age. The growth of ductal volume in
      relation to body mass was also biphasic with a 1st phase between 2 to 14 days (K
      = 0.88) and a 2nd phase between 14 to 70 days (K = 1.07). These results permitted
      us to conclude that the growth of the mouse pancreas is allometrically associated
      with the growth of body mass.

PMID- 9584519
TI  - Effect of intraperitoneal administration of zinc on C57/6J mouse liver--a light
      microscopic study.
AB  - Intraperitoneal administration of zinc chloride in vivo at 14 micrograms/g body
      weight (equivalent to 1/2 LD50) over a 3 week period induced an increase in liver
      weight. The mean weight of the livers in zinc-treated C57/6J mice was 50% higher
      than that of control animals. Image analysis revealed a concomitant and
      significant increase in the cross-sectional area and perimeter of the hepatocytes
      in the zinc-treated group. The mean cross-sectional area of hepatocytes in the
      zinc-treated mice was 337.2 +/- 4.3 microns2 as compared to 224.6 +/- 2.9
      microns2 in the control group (p < 0.05, Mann-Whitney test). The mean perimeter
      of hepatocytes in zinc-treated mice was 72.4 +/- 0.5 micron as compared to 58.9
      +/- 0.4 micron in control animals (p < 0.05). It would appear that subacute
      administration of zinc may result in increase in liver mass due to hypertrophy of
      the hepatocytes.

PMID- 9584520
TI  - Blastocyst implantation in rats: a morphological approach.
AB  - Very complex cellular events take place at the morphological and molecular levels
      both in the maternal and embryonic sites during blastocyst implantation. Although
      the morphological alterations in the gestational stages of the implantation site
      are well-known, mechanisms of the interaction between blastocyst and endometrial
      epithelium (apposition and adhesion stages) and penetration of the blastocyst
      into the endometrium have not yet been fully described. Therefore the present
      study was designed to determine these events morphologically throughout the
      implantational stages. To do this the endometrial tissues containing implantation
      sites from pregnant rats were taken 5 and 8 days after fertilization. In
      addition, non-pregnant rat endometrial tissues were also obtained in order to use
      as control. Tissues were processed for light and electron microscopy. Semi-thin
      and ultra-thin sections were stained using appropriate staining methods, and were
      evaluated under light and electron microscope. In the present study, interaction
      between trophoblast and luminal epithelium, penetration of the blastocyst into
      the endometrium, differentiation of germinal layers in the blastocyst and tissue
      alterations such as decidualization in the maternal site have been demonstrated
      morphologically. In conclusion, while blastocyst was implanted into the
      endometrium, distinct morphological changes occurred both in maternal and
      embryonic sites. The following stages of implantation were the development of
      germinal layers in the embryo and morphological changes in the maternal site
      leading to the placentation.

PMID- 9584521
TI  - A histological study of the organic elements in the human enamel focusing on the
      extent of the odontoblast process.
AB  - Topographic and tomographic studies were conducted on the organic elements
      occluded in the enamel of premolars removed from young orthodontic patients by
      using light (transmitted) microscopy, confocal scanning laser microscopy (CLSM),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM) on
      ultrathin sections and freeze-etching replicas, and energy dispersive
      spectroscopy (EDS) X-ray microscope (EDX) analysis. The present fine structure
      study aimed in particular to determine the fine structure of the enamel spindle
      and the extent of the odontoblast process. Organic elements in the ground
      sectioned enamel corresponding to simple projections and enamel rods/spindles,
      enamel tufts and lamellae were identified by conventional light microscopy and
      subsequently examined by CLSM. Both light microscopy and CLSM indicated that a
      number of enamel spindles were measured about 50 microns in length, some 4-7
      microns in thickness and were mostly confined to the cuspal summits and conformed
      to previous descriptions. SEM examination revealed some simple projections
      extending from the dentine into the enamel as well as clearly identifiable enamel
      spindles; the enamel spindles were structures intervening enamel prisms and
      showing morphological complexity by branching and convergence of the distal
      endings of the invading organic structure from dentinal tubules. EDX-analysis
      revealed that enamel tufts, lamellae, and spindles contained less phosphorus and
      calcium elements than enamel prisms. The enamel spindles had a higher content
      than tufts or lamellae, but this may be the result of contamination from
      surrounding enamel. Both conventional ultrathin-section and freeze-etching
      replica TEM evaluation of the dentino-enamel boundaries in particular suggested
      that simple projections and enamel rods/spindles were extensions of the
      odontoblast processes trapped in the enamel during early amelogenesis. In
      contrast, both SEM and TEM observations failed to identify dentinal tubule,
      peritubular (intratubular) dentine, membranous structures or lamina limitans
      surrounding the enamel spindles and simple projections occluded in the human
      enamel.

PMID- 9584522
TI  - Unmyelinated nerve fiber analysis of the human abducent nerve.
AB  - Unmyelinated nerve fibers of the abducent nerve have occasionally been observed
      with electron microscopes, but, to our knowledge, they have never been evaluated
      from the morphometric point of view. We analyzed the aging process of the
      unmyelinated nerve fibers in the human abducent nerve with the help of a new
      staining method suitable for morphometric research on the nervous system. We
      studied numbers and transverse areas of unmyelinated fibers of the abducent nerve
      in 10 cadavers. Our findings were that (1) these fibers were distributed
      diffusely, (2) their number decreased with age, and (3) the mean transverse area
      did not change with age. Most of the unmyelinated axons were thinner than the
      myelinated axons. These results may be important for analysis of clinical signs
      in relation to aging and ophthalmologic functions.

PMID- 9584523
TI  - Morphometric nerve fiber analysis and aging process of the human abducent nerve.
AB  - Myelinated nerve fibers of the human abducent nerve were analyzed with a new
      staining method that permits simultaneous observation of the axon and surrounding
      myelin sheath. The following equipment was employed for the measurements: an
      image-analyzing digitizer, a microscope equipped with a drawing tube (or camera
      lucida), and a computer for data storage and statistical analysis. The numbers,
      transverse areas, and circularity ratios of axons were measured in 10 human
      abducent nerves. The average number was 1,997 with a definite decrease with age,
      and the average area was 3.90 micron 2.

PMID- 9584524
TI  - Lyme disease.

PMID- 9584525
TI  - Early identification and intervention for children who are hearing impaired.
AB  - Early identification of and intervention for all children who have hearing
      impairments remain unattained goals in the United States. Physicians typically
      are the first persons to obtain the medical and family history of infants and
      children and are the primary professionals confronted with parental concerns
      about hearing loss. Heightened awareness of the common causes of hearing loss in
      infants and children can facilitate prompt and appropriate referrals to
      audiologists when hearing loss is suspected. A strong and interactive
      relationship between physician and audiologist is needed to attain the common
      goals of providing the earliest and best possible diagnosis of and optimal
      management for hearing impaired pediatric patients.

PMID- 9584526
TI  - Contact dermatitis.

PMID- 9584528
TI  - Index of suspicion. Case 1. Vaginal foreign body.

PMID- 9584527
TI  - Rocky Mountain spotted fever.

PMID- 9584529
TI  - Index of suspicion. Case 2. Rabies.

PMID- 9584530
TI  - Index of suspicion. Case 3. Wegener granulomatosis.

PMID- 9584531
TI  - Rabies vaccine.

PMID- 9584532
TI  - Temperament and school performance.

PMID- 9584533
TI  - Measles vaccine.

PMID- 9584534
TI  - Hormonal changes in the postpartum and implications for postpartum depression.
AB  - The months following childbirth are a time of heightened vulnerability to
      depressive mood changes. Because of the abrupt and dramatic changes occurring in
      hormone levels after delivery, many studies have examined the role of hormonal
      factors in postpartum depression. The authors review the literature on potential
      hormonal etiologies in postpartum depression, in particular for progesterone,
      estrogen, prolactin, cortisol, oxytocin, thyroid, and vasopressin. While evidence
      for an etiologic role is lacking for most hormones, changes in certain hormonal
      axes may contribute to depressive mood changes in some women following
      childbirth.

PMID- 9584535
TI  - Prevalence of posttraumatic stress disorder in women with breast cancer.
AB  - This study investigated whether diagnosis and treatment of breast cancer produced
      posttraumatic stress disorder (PTSD) in adult women. One hundred sixty women with
      early stage node-negative breast cancer completed self-report questionnaires and
      underwent a full diagnostic assessment (Structured Clinical Interview for DSM-III
      R). PTSD symptoms were common; however, only 3% of the women interviewed met
      stringent criteria for cancer-related PTSD in the 4-12 months following the
      completion of their medical treatment. Thus, breast cancer produced considerable
      distress, but low rates of PTSD, and may not fit well as a Criterion A stressor
      event for PTSD. Caution is urged for an assumption of a PTSD diagnosis based on
      self-reported symptoms.

PMID- 9584536
TI  - Psychopharmacological treatment of delirium to restore mental capacity.
AB  - The authors report four patient cases of delirium in which medications were used
      to restore mental capacity when life-or-death treatment decisions were required.
      Although extensive literature on substituted judgment exists for delirium and
      depression compromising capacity to make competent decisions, the authors could
      locate no articles proposing aggressive delirium treatment for restoring
      patients' capacity to participate in their own care. Without surgical
      intervention, all four of the authors' patients faced imminent death. Without
      psychopharmacologic banishment of the patients' deliria, proxies would have been
      asked whether the patients should undergo potentially lifesaving but high-risk
      procedures. The patients would have lost the opportunity to express their wishes
      about heroic lifesaving medical measures.

PMID- 9584537
TI  - Methylphenidate in post liver transplant patients.
AB  - Methylphenidate (Ritalin, manufacturer: Ciba/Geigy) has been shown effective for
      the treatment of depression in various medically ill populations, but to our
      knowledge its use in organ transplant patients has not been described. The
      authors retrospectively reviewed clinical records of the first eight inpatients
      who received methylphenidate for treatment of depressive and/or cognitive
      symptoms in the post liver transplant period at Mount Sinai Medical Center.
      Target symptoms included psychomotor and cognitive slowing as well as lack of
      motivation for recovery, poor rehabilitation effort, social withdrawal, and
      apathy. A positive response was noted in seven patients, and in one patient the
      response was equivocal. Side effects noted were increased blood pressure (N = 2)
      and subjective restlessness/agitation (N = 3). Methylphenidate appears to be an
      effective, rapidly acting agent in this setting at dosages of 10-20 mg/day, with
      minimal side effects. Methylphenidate may have a significant role in the care of
      an ever-increasing population of organ transplant recipients with multiple
      medical problems and associated disabilities.

PMID- 9584538
TI  - Immunosuppressant neurotoxicity in liver transplant recipients. Clinical
      challenges for the consultation-liaison psychiatrist.
AB  - Neuropsychiatric problems are common among liver transplant recipients, and
      immunosuppressant neurotoxicity is an important etiologic factor in the
      posttransplant period. Four typical cases of immunosuppressant neurotoxicity are
      presented from the clinical experience of the University of California, Los
      Angeles-Dumont Liver Transplant program. All patients presented with acute
      behavioral symptoms and received urgent psychiatric consultation; each proved to
      be suffering from a variant of immunosuppressive-related neurotoxicity.
      Correlative neuroimaging studies and descriptions of clinical course are
      included. Psychiatrists are urged to become familiar with the signs, symptoms,
      differential diagnosis, neuroimaging findings, and management of
      immunosuppressive neurotoxicity and secondary psychiatric disorders in solid
      organ recipients.

PMID- 9584539
TI  - Effect of intervention for psychological distress on rehospitalization rates in
      cardiac rehabilitation patients.
AB  - Psychosocial factors affect the development of coronary heart disease and
      morbidity and mortality of patients with known coronary heart disease. A prior
      study has shown that psychological distress in patients with known coronary heart
      disease increased medical and economic costs. This study examined the effects of
      commonly available psychological interventions offered to patients entering
      cardiac rehabilitation after hospitalization for angina, myocardial infarction,
      angioplasty, or coronary artery bypass grafting. A total of 380 patients were
      screened with the Symptom Checklist-90-Revised (SCL-90-R). Those with T-scores >
      or = 63 (> or = 91 percentile) on the General Severity Index (GSI) subscale were
      randomly assigned to usual care or special intervention. Special intervention
      included a psychiatric evaluation, plus one to seven sessions of behavioral
      therapy. The percentage of patients rehospitalized for cardiac symptoms within 12
      months of psychological evaluation was 43% for special intervention and 40% for
      usual care (NS). A correction for crossover between the treatment groups resulted
      in a favorable trend toward intervention, with 35% of the psychologically treated
      patients rehospitalized vs. 48% of the untreated patients (NS). Although there
      was a nonsignificant reduction of the SCL-90-R's GSI T-score, the depression
      score was significantly reduced in the special intervention group.

PMID- 9584540
TI  - Pseudoseizures, families, and unspeakable dilemmas.
AB  - Fourteen videotaped family interviews of patients with diagnosed pseudoseizures
      were studied to determine the relationship of the symptoms to unspeakable
      dilemmas as forced choices imposed by family or social circumstances under
      conditions that also require the ensuing distress to be hidden. An unspeakable
      dilemma was evident in 13 of 14 interviews, with the patient the most silent
      family member in 13 interviews. In six cases, there was revealed a realistic
      threat of physical or sexual assault to a person involved in the problem,
      although not always the patient. These findings point to an important role for
      family therapy skills in the evaluation and treatment of pseudoseizures.

PMID- 9584542
TI  - Spontaneous pneumothorax in anorexia nervosa.

PMID- 9584541
TI  - Psychiatric care in an AIDS nursing home.
AB  - Of the first 675 persons admitted to a new acquired immunodeficiency syndrome
      (AIDS) nursing home, 423 were seen in psychiatric consultation. They ranged in
      age from 22 to 70 years. Most were coping with multiple losses of health,
      fitness, homes, careers, loved ones, strength, and functional capacity. All had
      multiple and severe medical illnesses. Of the 423 persons evaluated, 422 (99.8%)
      had 1 or more psychiatric disorders. Three hundred fifty-one (83%) had a
      diagnosis of dementia, 349 (82.5%) substance abuse, 276 (65%) psychiatric
      diagnoses other than cognitive or substance abuse, and 61 (14.4%) delirium. The
      individuals admitted to the AIDS nursing home were younger, more medically and
      psychiatrically ill, on more complex medical regimens, and had a higher
      prevalence of both dementia and substance abuse than those in a separate study of
      geriatric nursing homes.

PMID- 9584543
TI  - New-onset panic disorder after right thalamic infarct.

PMID- 9584544
TI  - Posttraumatic stress disorder and obstructive sleep apnea syndrome.

PMID- 9584545
TI  - Prevalence rate of musical hallucinations in a general hospital setting.

PMID- 9584546
TI  - Behavioral changes and affective instability associated with adult-onset
      adrenoleukodystrophy.

PMID- 9584547
TI  - Restless leg syndrome exacerbated by sertraline.

PMID- 9584548
TI  - The SF-36 profile and health-related quality of life: an interpretative analysis.
AB  - The purpose of this investigation was to explore the relationship between the SF
      36 scales and a direct, category-scaling, self-evaluation of health-related
      quality of life in a sample of healthy persons. The study of the relationship
      between the two provides a deeper insight into the structure and meaning of the
      SF-36 profile and explores its interpretability in terms of a comprehensive,
      subjective evaluation of health. Furthermore, this study leads to a preliminary
      interpretation of the profile in terms of a utility scale.

PMID- 9584549
TI  - The role of anxiety and depression in quality of life and symptom reporting in
      people with diabetes mellitus.
AB  - Although quality of life evaluations are widely used throughout medicine,
      relatively little is known about the psychological processes involved in making
      these judgements. What is known is that quality of life judgements are not
      straightforwardly associated with objective measures of health status or
      clinician ratings. In particular, patient affect appears to be associated with
      quality of life ratings but whether this relationship is secondary to physical
      health or not is controversial. The aim of this study was to determine the role
      of anxiety and depression in the reporting of quality of life in a group of
      patients with diabetes mellitus. One hundred consecutive patients with diabetes
      (insulin-dependent diabetes mellitus n = 36 and non-insulin-dependent diabetes n
      = 64) were assessed using a self-report measure of quality of life, a symptom
      checklist and a questionnaire measure of anxiety and depression. In addition,
      they were independently rated for their level of physical impairment. The results
      showed that depression and, to a lesser extent, anxiety were significantly
      related to self-reported quality of life even when the differences in physical
      health and age were controlled for statistically. This study shows that,
      independent of the level of physical illness, affect, particularly depressive
      affect, is an important factor in the determination of quality of life.

PMID- 9584551
TI  - Norms for the physical and mental health component summary scores of the SF-36
      for young, middle-aged and older Australian women.
AB  - The SF-36 was developed in the USA to provide an eight-scale health profile and
      two component summary scores representing physical and mental health. The
      published norms and scoring procedures are based on data from the US general
      population. The Australian Longitudinal Study on Women's Health (Women's Health
      Australia) undertook a survey in 1996 of approximately 42,000 Australian women in
      three age groups of 18-22, 45-49 and 70-74 years and provided age- and gender
      specific norms for the SF-36 health profile. From these data, factor weights and
      factor score coefficients were calculated for these age- and gender-specific
      populations of Australian women. Thus, component summary scores for physical and
      mental health can now be calculated using a formula standardized to the relevant
      Australian population. This will facilitate the interpretation of the physical
      and mental health component summary scores in the Australian context and will
      allow meaningful comparisons within the young, middle-aged and older cohorts of
      Australian women in the Australian Longitudinal Study on Women's Health.

PMID- 9584550
TI  - The Medication Attribution Scale: perceived effects of antiretrovirals and
      quality of life.
AB  - This report describes the development and validation of an instrument to assess
      the attributions human immunodeficiency virus (HIV)-infected persons who are
      currently taking antiretrovirals make about the effects of these medications. The
      specific limitations in functioning that the subjects attributed to the effects
      of medication were assessed. The scores on a ten-item instrument were found to
      have high internal consistency reliability and to be related to beliefs about the
      benefits and barriers to taking antiretrovirals. The attribution that the use of
      antiretrovirals had contributed to an increase in depressive symptoms was related
      to reports of having temporarily discontinued use of antiretrovirals during the
      preceding month. The summated score on the Medication Attribution Scale (MAS) and
      other subscale scores were not found to predict self-reported intentional
      alterations of treatment regimens. Multiple regression analyses indicated that
      negative attributions about the effects of medications contributed to the amount
      of variance in quality of life explained over and above that explained by
      perceived health status and level of symptomology.

PMID- 9584552
TI  - Use of the Short Form-36 to detect the influence of upper gastrointestinal
      disease on self-reported health status.
AB  - Patient-centred outcome measures such as the Short Form-36 (SF-36) have been
      developed to assess the impact of ill health and medical interventions on self
      reported health status. The objective of the study was to assess the impact of
      gastrointestinal disease upon health status as measured by the SF-36 physical and
      mental health component scores (PCS and MCS) and to assess whether these
      component scores might be an appropriate outcome measure for use in clinical
      research in gastroenterology. The subjects were 364 patients aged between 18 and
      64 years who had been prescribed proton pump inhibitors (PPIs) by general
      practitioners in Oxfordshire. The general practices participating identified
      patients who had been prescribed PPIs. The data were abstracted from the general
      practice medical records of these patients concerning gastrointestinal diagnoses
      and other prescribed medications. The patients were sent the SF-36 questionnaire
      by post and the PCS and MCS scores were derived, which were adjusted for age and
      sex and compared with the scores of the general population of the Oxford region.
      Co-morbidity was assessed by the extent to which non-gastric medications were
      also used. The commonest diagnoses were oesophagitis/gastro-oesophageal reflux
      and indigestion. People with these diagnoses had significantly lower health
      status than the general population. Differences persisted when the results were
      controlled for the possible effects of co-morbidity. It was concluded that the SF
      36 is sensitive to the impact of gastrointestinal disease on health status.

PMID- 9584553
TI  - Development of a shortened version of the Breathing Problems Questionnaire
      suitable for use in a pulmonary rehabilitation clinic: a purpose-specific,
      disease-specific questionnaire.
AB  - One hundred and thirty-eight chronic obstructive pulmonary disease (COPD)
      patients completed the Breathing Problems Questionnaire (BPQ) before and after a
      comprehensive programme of rehabilitation. Examination of the changes on
      individual items showed improvement on 22 items, of which four items were
      significant at p < 0.05 and deterioration on nine items, of which two were
      significant at p < 0.01. All deteriorating items were consistent with lifestyle
      adaptations encouraged as part of the rehabilitation programme. We examined the
      psychometric properties of a reduced ten item version of the BPQ limited to the
      items most sensitive to change. We recommend the purpose-specific, disease
      specific COPD scale for measuring change in pulmonary rehabilitation assessment
      in contrast to the longer 33 item questionnaire, which, however, may be more
      useful for cross-sectional assessment.

PMID- 9584554
TI  - The responsiveness of disease-specific and generic health measures to changes in
      the severity of asthma among adults.
AB  - The objective of the study was to compare the validity of asthma-specific and
      generic health outcome measures in relation to changes in the severity of asthma
      and to treatment. Adult patients (n = 142) participating in a randomized placebo
      controlled trial at six clinics were assessed at baseline, prior to the
      withdrawal (placebo) or continuation of treatment with Vanceril and again after 8
      weeks. The criterion measures of change in severity included pulmonary function
      expressed as the percent predicted FEV1, five physician-assessed asthma severity
      measures (cough, chest tightness, wheezing, shortness of breath and overall
      condition) and two patient-assessed severity measures (night-time symptoms and
      overall symptoms). The 8 week change scores were estimated for all generic and
      specific measures and the results were compared across groups of patients who did
      and did not change in terms of clinical criteria of disease severity and across
      treatment groups. The responsiveness of each generic and specific measure was
      estimated independently using the relative validity (RV) methodology, which
      compares F-ratios for the mean change scores across measures in analyses of the
      same comparison groups. RV coefficients estimate how much worse each measure
      discriminated between comparison groups, relative to the best measure (RV = 1.0).
      Four standardized asthma-specific measures and a total scale score (based on the
      Marks questionnaire), an individualized asthma-specific scale measuring
      limitations in activities most important to each patient (based on the Juniper
      method) and two newly-developed scales measuring physical and psychosocial
      symptoms were used as outcome measures, generic health outcome measures included
      eight functional health and well-being scales as well as the physical and mental
      health summary scales from the SF-36 health survey. A standardized asthma
      specific scale was most valid in discriminating between groups of patients who
      did and did not change according to all of the clinical criterion variables
      studied and in discriminating between treated and untreated groups. Different
      scales performed best, depending on the clinical criterion. The asthma-specific
      Marks breathlessness scale was significant in all nine comparisons (RV = 0.62
      1.0) and was most valid in discriminating between groups in six of nine tests.
      The overall scale also performed well in all comparisons (RV = 0.58-1.0). The
      newly-developed physical symptoms scale was significant in discriminating between
      groups in eight out of nine tests (RV = 0.52-1.0) and was most valid in three of
      the nine, including the treatment comparison. The psychosocial impact scale
      discriminated significantly in eight of the nine comparisons (RV = 0.16-0.38),
      but was less valid than other specific measures. The asthma-specific
      individualized activities scale discriminated significantly in seven of the nine
      tests, but performed less well than the other specific measures (RV = 0.21-0.35)
      and was not significant in the treatment comparison. One or more SF-36 scales
      discriminated significantly between groups in all nine comparisons. Two of those
      scales (physical functioning and role-physical) were consistently more valid than
      the others (RV = 0.17 and 0.58, respectively) and were the only two generic
      scales that discriminated between groups of patients defined in terms of changes
      in FEV1 (RV = 0.26-0.58). The SF-36 physical summary scale discriminated
      significantly between groups in all nine comparisons (RV = 0.19-0.61) and was the
      most valid generic measure in the treatment comparison (RV = 0.55). The SF-36
      mental summary scale was significant only for the two patient-assessed changes in
      disease severity (RV = 0.31 and 0.32) and for physician-assessed overall severity
      (RV = 0.12). A comprehensive battery of generic and specific measures is likely
      to be most useful in understanding the impact of changes in disease severity on
      the functional health and well-being of adults with asthma, a

PMID- 9584555
TI  - French cross-cultural adaptation of the Health Utilities Indexes Mark 2 (HUI2)
      and 3 (HUI3) classification systems. Clinical and Economic Working Groups.
AB  - The McMaster Health Utilities Indexes Mark 2 (HUI2) and 3 (HUI3) are
      multiattribute health classification systems, for which multiattribute preference
      functions have been developed in Canada. They provide a comprehensive instrument
      for use in economic evaluations and population health survey studies. This paper
      reports on the first results on the adaptation of the HUI2 and HUI3 systems cross
      culturally and the assessment of the validity and reliability of the French self
      report questionnaire in different patient populations. The cross-cultural
      adaptation included translation, backtranslations, an expert consensus meeting
      and pre-test with a few patients and healthy subjects in order to produce a
      conceptually equivalent French version of the 15 question self-report
      questionnaire and the HUI2 and HUI3 classification systems. Different groups of
      patients attending specialized clinics (n = 709) completed the questionnaire and
      another generic questionnaire (the Sickness Impact Profile (SIP)) for validity
      assessment. Physicians and patients were also asked for a global subjective
      assessment of the patient's health status. The French questionnaire was well
      received by the patients. The criterion and convergent validities of both
      classification systems (correlations with the patients' and physicians'
      assessments and with the responses to the SIP questionnaire) were satisfactory.
      The internal consistency was acceptable too (Cronbach's alpha = 0.81), as was the
      3 day test-retest reproducibility. These first results authorize careful use of
      the 15 question self-report questionnaire in French. An assessment of the
      multiattribute preference function for the HUI3 system in France will be the
      study's next objective.

PMID- 9584556
TI  - Self-reported quality of life for patients with progressive neurological
      diseases.
AB  - Progressive neurological diseases influence the life situation of patients either
      totally or partially. Such patients' own ratings of their life situation and well
      being were made using a health-related quality of life HRQoL instrument called
      Quality of Life: status and change (QLsc). In general the interviewees rated
      their life domains in terms of positive response alternatives and no subgroups
      were found, e.g. with the same diagnoses, periods of sickness or age. The results
      suggest that the interviewees' experience of quality of life (QoL) is subjective
      and individual. The interviewees who had been to the rehabilitation centre
      several times rated their quality of life, in terms of positive response
      alternatives for the items covering overall experiences of bodily health, well
      being and their whole life as well as for items in the social domain, to a
      greater extent than those who were visiting it for the first time.

PMID- 9584558
TI  - Effects of altering the time of administration and the time frame of quality of
      life assessments in clinical trials: an example using the EORTC QLQ-C30 in a
      large anti-emetic trial.
AB  - Previous studies conducted by our group suggested that the ability to demonstrate
      an impact of emesis control on quality of life might depend upon when an quality
      of life instrument was administered in relation to chemotherapy and on the time
      frame of the questionnaire. This study was conducted to address this issue. Six
      hundred and fifty patients receiving moderately emetogenic chemotherapy in a
      randomized trial comparing a variety of anti-emetic regimens were allocated to
      four different modes of administration (days 4 and 8; 3 and 7 day time frames) of
      the QLQ-C30. Patients who completed the questionnaire at the time of maximal
      impact of chemotherapy (day 3) were more likely to report deterioration in
      quality of life. Patients who completed questionnaires at day 8 were more likely
      to report deterioration in quality of life if their questionnaire had a 7 day
      time frame rather than a 3 day time frame. Patients receiving more effective anti
      emetic therapy had better quality of life. It was concluded that better anti
      emetic control improves quality of life after moderately emetogenic chemotherapy.
      In studying quality of life in situations where the impact of treatment waxes and
      wanes, careful attention needs to be paid to scheduling the administration of
      questionnaires and to their time frame.

PMID- 9584557
TI  - Knowledge, self-management, compliance and quality of life in asthma: a cross
      sectional study of the French version of the Asthma Quality of Life
      Questionnaire.
AB  - The Asthma Quality of Life Questionnaire (AQLQ) is a well-validated instrument.
      Our objectives were to explore the cross-sectional validity of the French
      version, using usual outcomes of asthma, as well as assessment of knowledge of
      asthma, self-management and compliance. A self-administered version of the AQLQ
      was given to 124 consecutive patients recruited from two out-patient clinics and
      an emergency room in order to reflect a wide range of asthma severity. The other
      outcomes of asthma measured were the FEV1, patient-perceived asthma severity
      using a visual analogue scale, compliance, knowledge of asthma condition and self
      management autonomy. Correlations were predicted before analysis ( r > 0.5,
      strong correlation, ++ r = 0.35-0.5, moderate correlation and + r = 0.20-0.35,
      fair correlation). The AQLQ scores correlated moderately to strongly with asthma
      severity and fairly with the pulmonary function results. Of the behavioural
      outcomes assessed, only knowledge of asthma correlated fairly with the AQLQ
      scores, as expected. This study of the French version of the AQLQ, while showing
      similar cross-sectional correlations with functional assessment and asthma
      severity to those observed with the original English version, suggested in
      addition a positive association between quality of life and knowledge of asthma.

PMID- 9584559
TI  - [A review of Sante publique in 1997].

PMID- 9584560
TI  - [Health and violence as perceived by young people, a study of the Parisian
      region].
AB  - We know better the violences made by the youngs than those they suffer from. The
      purpose of this study is to assess, as for a city surrounding Paris, the
      prevalence of the violences they felt and its relation with the psychic
      uneasiness. Some 344 youngs (from 15 to 25 years old) selected in the city, have
      filled in an autoquestionnaire. It has shown that 61.6% of them have already
      suffered from violences, among them 44.5% from adults and what is more from
      institutional adults. 13.7% of the selected youngs were victims of regular
      violences in school sphere and 12.8% in urban environment. The expression of a
      psychic uneasiness is linked to the previous violences they have felt. The
      feeling of call for help by a psychologist or a psychiatrist is in relation with
      the past psychic discomfort and not with the past suffered violences.

PMID- 9584561
TI  - [Health care access of young people not attending school in precarious
      situations].
AB  - The legislations of July 1992 and January 1993 and the decree of 27th March 1993
      offer the possibility for medical care to all, including many young people who do
      not have any rights when they need urgent medical attention. This study covers
      the proposals of professionals from the Languedoc and Roussillon regions who are
      responsible for the social and professional insertion of young people and their
      rights of access to medical care. These professionals serve both as the principal
      means of access to medical aid for young people and as the main obstacles to this
      aid which occurs as a result of the interaction between professional occupational
      practice and the behaviour of the young people concerned. From this study the
      following conclusions were drawn: this legislation excludes alien young people in
      an illegal situation; the potential availability of these rights is limited by
      arbitrary decision in administration; the period of coverage of these rights is
      long and complex; the financial obstacle is real for all young people who do not
      have free access to medical aid; the obstacles resulting from social interactions
      are frequent; there are many holes in the institutional network.

PMID- 9584562
TI  - [Hospital discharge for elderly persons: a cross-sectional study in Alsace].
AB  - The objectives of this study are to analyse in the Alsacian region the needs of
      people aged 75 years old and over after a stay in hospital. It is also to
      identify the matching point between the ideal patient discharge and the one
      feasible in reality. Finally, if no matching point is found, the study examines
      the reasons for this. This is an exhaustive overview conducted 8th December 1994
      in the 96 Alsacian hospitals on all patients aged 75 and over than 10 days in
      short stay services and over 20 days in medium stay services. Thus 965
      questionnaires were analysed. On leaving hospital, 60% of ideal discharge are
      feasible. This percentage varies according to the kind of discharge. From 18% for
      the Alzheimer units it reaches 91% for "home stay without arrangement". When the
      ideal discharge is "long stay", it is often not feasible due to structural
      causes. On the contrary, when going home is the ideal solution, this is often not
      feasible due to lack of motivation either from the patient or their family.

PMID- 9584563
TI  - [Effects of the improvement in the quality of care in a university hospital].
AB  - In charge with the development of quality assurance in a university hospital, the
      authors have recorded actions realised in medical departments to improve quality.
      A first questionnaire was sent to every physician (340) and every chief nurse
      (170). The 126 answers allowed to pick 467 actions out and to identify 72
      professionals who were involved in quality actions. These last ones have been
      asked during semi-directive interviews in view to describe those actions, their
      results and difficulties encountered. The main actions consisted in writing
      procedures (197), animating working groups (84) or department reunions (54),
      realising studies (54) or measuring indicators (33). This study shows the
      professionals' dynamism who spontaneously develop actions to improve the quality
      of care. It also shows the limits of these actions because of a lack of specific
      resources and methods.

PMID- 9584564
TI  - [The quality of voter registration lists and participation factors during a
      community survey of elderly people].
AB  - Electoral registers are often used to randomly select persons for epidemiological
      surveys. The importance and the different types of inaccurate informations found
      in these lists were studied during a survey among an elderly population of 5,161
      persons aged 75 and over in Tarn area. Information was found to be inaccurate in
      13.7% of the cases (people who have died 3%, moved out of the area 10.5%,
      inaccurate date of birth 0.2%), this increased with age and with size of the
      parish. The overall participation was 65.3%. The corrected participation (with
      exclusion of inaccurate information) was 75.7% and was higher in rural parishes
      and where the help of local organizations of elderlies was available.

PMID- 9584566
TI  - [Cannabis consumption in young people living in Brussels: observational
      conclusions drawn from a preliminary study].
AB  - A qualitative study was carried out to explore the adolescents' representations
      of cannabis and related behaviors. Twenty-two young people aged 13 to 18 years
      and living in Brussels were interviewed using a half structured interview
      guideline. The analyse showed that there are three types of behaviors related to
      cannabis use: the non-users, the experimenters and the users. Parents, the school
      and peers seem to be specific determinants of cannabis use as well as the main
      information channels about this product. These preliminary results already lead
      ways to prevention: training of parents and teachers and school improvement.

PMID- 9584565
TI  - [Cardiac surgery in France (supply, service and needs response): a national
      survey].
AB  - This paper describes the results of a national study of the 70 french cardiac
      surgery units. This study was required by the ministry of health in order to
      prepare the planning process of cardiac surgery in France. Results concerning the
      year 1994 show important regional variations of resources among the country. The
      number of interventions has increased three fold in 15 years (from 13,000 to
      38,000 a year). The share of the different indications are constant
      (coronaropathy: 53%; valvulopathy: 36%; congenital: 8%). Patient flows across
      french regions represent 15% of the interventions. Regional intervention rates
      per capita range from 45 to more than 80 for 100,000 inhabitants. French cardiac
      surgery is, in fact, organized at a multiregional level and the regional
      intervention rates are not correlated with mortality or demographic rates.

PMID- 9584567
TI  - [Methods and perspectives of AIDS prevention among teachers of secondary schools
      in the village of Namur].
AB  - In 1994, ASBL Namur-Entraide-Sida has been involved in a survey through
      questionnaires for teachers of the whole high schools in Namur (Belgium). Its
      purpose was to better notice what sort of viewpoints and modalities in preventing
      youngs from aids were developed or not during the school. From 2,435
      questionnaires, 617 (25%) have been returned and analysed. Among the main
      results, the teachers' feeling was the professional training is adapted enough in
      order to response to this item in school and they also hope to improve the
      efficiency of the inside and outside collaborations. This survey has pointed out
      the teachers' prime perception of the risks for the pupils to be infected and
      that, in relation with their own exposition level. This last result leads us to
      wonder about the indicators which from the prevention from aids has been
      developed among the school children since the ten latest years. It has not to be
      forgotten that the urgency of the events is able to hide the stakes of the
      educative relation and ethic about the teenagers' prevention.

PMID- 9584568
TI  - [Prognostic factors in stomach carcinoma].
AB  - The classical prognostic factors of the pTNM system are still most valid.
      Nevertheless, vascular invasion as well as the molecular marker E-cadherin proved
      to be independent new prognostic factors responsible for a significant shift in
      patient survival. Thus, in pTNM-stage II patients, a highly significant drop in
      survival is observed when patients showing no E-cadherin expression and at the
      same time vascular invasion are compared with E-cadherin-positive patients who do
      not show vascular invasion (Fig. 11). These conspicious shifts in survival
      underline the necessity to continue our search for new molecular and non
      molecular markers which in future may help us to predict the outcome of gastric
      cancer patients more precisely and more individually.

PMID- 9584569
TI  - [How accurate is preoperative staging as a basis for treatment decisions in
      gastric carcinoma?].
AB  - The treatment of advanced gastric carcinoma by various neoadjuvant and adjuvant
      multimodal therapy regimes is under current investigation to improve the poor
      outcome of these patients. Therefore, pretherapeutic tumor staging according to
      the TNM classification is essential for the optimal application of various
      therapeutic modalities. According to recent studies, endoscopic ultrasonography
      (EUS) is the most sensitive technique in measuring tumor infiltration (T
      staging). In addition, although less reliable compared to the T-staging, the
      sensitivity of EUS in assessing lymph node status (N-staging) is superior to
      computed tomography and conventional ultrasound. Pretherapeutic laparoscopic
      investigation may give additional important information about tumor stage. This
      overview describes the significance of various diagnostic techniques that can be
      applied in tumor staging investigations.

PMID- 9584570
TI  - [Stage-adapted radical principles in gastric carcinoma].
AB  - The aim of any surgical approach to gastric carcinoma should be a complete
      resection with no residual tumor left behind, that is, a R0-resection according
      to UICC. Complete tumor resection in this respect refers to the primary tumor as
      well as to the lymphatic drainage and requires an adequate safety margin. The
      indications for surgical therapy of gastric cancer and the choice of procedure
      should consequently be guided by the tumor stage. This requires accurate
      preoperative staging, which can today be achieved with endoscopic ultrasonography
      and surgical laparoscopy. Gastric carcinoma stage IA (mucosa carcinoma) can be
      cured by local excision. In patients with tumor Stages IB (submucosa carcinoma),
      II, and IIIA, lymph node metastases are common. Based on the available data, this
      group of patients benefits from radical resection and D2 lymph node dissection.
      The overall 5-year survival rate of 50% for the large number of patients
      undergoing gastric resection for cancer seems to demonstrate convincingly the
      value of extended lymphadenectomy. In patients with advanced gastric carcinoma,
      that is, tumor stages IIIB and IV, a complete tumor removal usually can not be
      achieved by surgical dissection. Neoadjuvant therapeutic modalities should
      consequently be assessed in these patients. Based on tumor location and growth
      pattern, a total gastrectomy is the procedure of choice in patients with middle
      and proximal third gastric cancer. A subtotal gastrectomy may be performed in
      patients with tumors of the distal third and "Laurens intestinal type" growth
      pattern. The distal site of the main lesion must be investigated carefully to
      ensure that incidental concomitant lesions are not overlooked. Depending on the
      individual tumor situation, the gastrectomy can be extended toward varying
      portions of the distal esophagus or the pancreas, preserving splenectomy and
      resection of the retroperitoneal lymph nodes. The high incidence of locoregional
      recurrences and distant metastases after curative surgery for gastric cancer
      calls for improved locoregional control and systemic adjuvant treatment.

PMID- 9584571
TI  - [Neo-adjuvants, adjuvants and palliative therapy for gastric carcinoma].
AB  - Patients with gastric cancer have a poor prognosis. Because curative surgery is
      often impossible (metastatic disease) or extremely difficult (locally advanced
      tumors), and the majority of patients undergoing curative resection relapse,
      chemotherapy has been actively studied in gastric cancer. Several combination
      chemotherapy regimens have been developed with high activity in locally advanced
      and metastatic disease. Among them are 5-fluorouracil (5-FU) plus high dose
      methotrexate plus doxorubicin (FAMTX). It represents the reference treatment in
      many clinical trials. Recent schedules like etoposid plus cisplatin (EAP);
      etoposid plus leucovorin plus 5-FU (ELF) and epirubicin plus cisplatin plus 5-FU
      (ECF) show encouraging response rates, their toxicity is considerable, however.
      Randomized trials comparing chemotherapy with best supportive care showed an
      increase in overall survival and in quality-of-life. Up to now adjuvant
      chemotherapy has failed to improve survival as compared with surgical controls.
      Only half of the patients with locally advanced gastric cancer (LAGC) undergo
      macroscopic and microscopic tumor-free resection. Preoperative chemotherapy has
      shown very promising results even in patients who had primarily unresectable
      tumors. Approximately half undergo R0 resection after downstaging induced by
      active chemotherapy and the long-term survival rises to about 20%. There are
      hopes that the newest regimes may do this: new cytostatic drugs and the immuno
      chemical approach to combine cytostatic drugs with cytokines will be of great
      importance.

PMID- 9584572
TI  - [The influence of interferon therapy on CNS function--from the aspects of
      quantitative EEG and biogenic amines].
AB  - Various CNS side effects have been reported since interferon (IFN) was introduced
      for the treatment of chronic active hepatitis C (CAHC) patients. Most reports of
      EEG changes after IFN therapy were inspective, and there is no report of
      quantitative EEG analysis. In this study, changes in quantitative EEG and
      biogenic amines after IFN therapy were studied to enable identification of CNS
      side effects early in CAHC patients. Before and 7 days after IFN therapy, EEG
      records and plasma and urinary amines were examined in 36 CAHC patients (46.9 +/-
      12.3 years, 29 men and 7 women) who were hospitalized for the IFN therapy. After
      IFN therapy, no notable change in biogenic amines was recognized. On EEG, 13
      patients (39.4%) showed increased slow wave activities and 2 patients (6.1%)
      showed paroxysmal discharges after IFN therapy. On quantitative EEG, the patients
      showed significantly increased absolute power in slow alpha, theta and delta
      bands and decreased absolute power in fast beta band (paired-T test). After IFN
      therapy, 4 of 36 patients developed psychiatric disorders; 2 patients developed
      depressive symptoms and 2 other patients developed manic states. One depressive
      patient and one manic patient had 6 Hz spike and slow waves before IFN therapy.
      On quantitative EEG, the other manic patient had shown significantly increased
      absolute power in slow alpha and decreased power in fast alpha and beta bands,
      and the other depressive patient had shown significantly increased absolute power
      in fast theta band and decreased power in fast beta band before the development
      of the psychiatric disorders. These results suggest that the changes of
      quantitative EEG, between before and 7 days after IFN therapy, can be useful in
      assessing the risk for the development of psychiatric symptoms induced by IFN
      therapy. It also suggests that patients with slight EEG abnormality such as a 6
      Hz spike and slow waves before IFN therapy need careful observation.

PMID- 9584573
TI  - [Obsessive-compulsive symptoms in children and pre-adolescents: clinical
      observation of inpatients].
AB  - I investigated the phenomenology of obsessive-compulsive disorder (DSM-IV) in 22
      children and pre-adolescents (8 boys and 14 girls, 6-15 years old, mean 12.2
      years) admitted to the psychiatric ward of Kanagawa Children's Medical Center
      between 1989 and 1996. Some patients were concomitantly diagnosed with psychotic
      disorder, or eating disorder (DSM-IV). Girls dominated boys, and all cases except
      a girl were over ten years old. Patients were divided into four types according
      to their obsessive-compulsive symptoms. Type I (7 cases, 31.8%): Recurrent idea
      and repetitive behavior were painful. The patients recognized these ideas and
      behaviors to be a product of their own mind. They also recognized the behavior to
      be excessive or unreasonable, and tried to resist at least while the symptoms
      were mild. Four patients showed good courses, but in three patients showed severe
      obsessive-compulsive symptoms that persisted for a long time after admission.
      Type II (13 cases, 59.1%) consisted of 2 subtypes. Type IIa (10 cases, 45.5%):
      The obsession or compulsion was recurrent and distressful, but insight into the
      problem was unclear or poor. We noted 4 Type IIa patients with this type resisted
      their symptoms, but the others' did not. This type was the most prevalent of the
      four types, and seemed to be the main type of obsessive-compulsive disorder among
      children and pre-adolescents. Type IIb (3 cases, 13.6%): Compulsion dominated
      obsession. The subjects experienced distress from their severe compulsion, but
      seldom complained of it. Furthermore, patients could hardly discern and resist
      their symptoms. So it resembled obsessive desire for the maintenance of sameness,
      or stereotypy in developmental disorders. Patients recognized the idea or the
      behavior to be the product of their own mind. Severe symptoms persisted for a
      long time after admission. Type III (2 cases, 9.1%): The patients experienced
      their recurrent idea and repetitive behavior as agonizing. They had insights that
      their obsession or compulsion was excessive or unreasonable, and tried to resist
      it. The symptoms were similar to those of psychoses, but patients did not have
      definite psychotic symptoms. Severe symptoms persisted for a long time after
      admission. Categorization according to obsession and compulsion supported the
      criteria for obsessive-compulsive disorder in DSM-IV. It showed concretely that a
      number of children and adolescents with severe obsessive-compulsive symptoms had
      marginal features of the symptoms. Of 20 cases excluding 2 cases classified as
      atypical type III, seven patients (35.0%) understood that their symptoms were
      excessive or unreasonable, and 10 cases (50.0%) showed objective resistance to
      their symptoms. However, insight or resistance to the obsessive-compulsive
      symptom was not as stable as that in adult patients with such symptoms, and
      vacillated during the course of the disease.

PMID- 9584574
TI  - ["Wish to die" and "right to die" in a case of schizophrenia].
AB  - Protection of life had long been the ultimate goal of medicine. Recently,
      patient's subjective judgement and self-determination also became another
      alternative principle. The situation is the same in psychiatry. Now, most
      patients with "wish to die" live in community, unless they show strong and urgent
      suicidal attempt. Meanwhile, "right to die" based on patient's self-determination
      has been established in the terminal state of cancer. Based on the same logical
      formulation, the "right to kill oneself" for patients with "intolerable
      psychological pain", is also asserted. Suicide as a right is now an impending
      agenda in psychiatry. A case of schizophrenia, who had killed her mother and who
      had "wish to die", was presented and discussed here. Conclusions were as follows:
      1) "Wish to die" was psychologically interpreted as "denial of wish to live". At
      least, this meant that "wish to die" was unable to be a clear and convincing
      evidence that "real will" to die actually existed. 2) Nevertheless, the therapist
      who was overwhelmed by the patient's "wish to die", felt that it was a patient's
      real will to die. 3) "Wish to die" was not a self-determination to die, but
      rather a patient's inquiry into the quality of therapy, if the therapist was able
      to tolerate the wish. 4) If everyone is supposed to have privacy that none can
      ever intrude, this right should be the one only for limiting excessive
      intervention of medicine, but not for helping suicide. 5) How to verbalize
      patient's "wish to live" hidden deeply at the very core of "wish to die" and how
      to support the patient's "wish to live", had a crucial importance in clinical
      practice of suicidal patients for therapists to confront "wish to die" together
      with the patient. 6) In general, it was discussed that the concept of "right to
      die" in suicide and in terminal states, had to be constructed in some different
      way.

PMID- 9584575
TI  - Contribution of cause-specific mortality to changing sex differences in life
      expectancy: seven nations case study.
AB  - During the last two decades some industrialized nations witnessed varying degrees
      of constriction in their sex gaps in overall life expectancy. We investigate this
      development by paying particular attention to the contributions of major causes
      of death to the change in the difference between 1970 and 1990. The analysis is
      based on the experiences of seven nations: Australia, United States, Sweden,
      England and Wales, Portugal, Hungary, and Japan. In the first four countries the
      gap has been narrowing during the last twenty years; in Hungary and Japan, the
      difference remains substantial and continues to expand; in Portugal the situation
      is characterized by a slowdown in the amount by which the sex gap is expanding
      over time. We apply decomposition analysis to answer the following questions: (1)
      What is the relative contribution of major causes of death to sex differences in
      average length of life within broad age categories? (2) How do the contributions
      of age and cause of death vary across time to either widen or narrow the sex gap
      in survival? (3) How do the patterns of cause contribution vary across societies?

PMID- 9584576
TI  - Covariates of infant mortality in China: an exploratory approach.
AB  - To elucidate the nature of the relationship between infant mortality in China and
      a variety of covariates using data from the 2/1000 Chinese Fertility Survey, we
      use a logistic regression model where the covariates are transformed with the
      help of Alternating Conditional Expectation (ACE) algorithm. This approach is
      used to overcome the general problem in multivariate regression analysis of
      coding the independent variables so that relationship between independent
      variables and response variables is best described, rather than coding such
      variables in an arbitrary way. The study demonstrates the procedures and
      usefulness of the ACE guided transformation in multivariate analysis. The
      transformed covariates are then used to estimate the effects of a series of
      socioeconomic and demographic factors collected in the study of infant death in
      China. The study shows that after appropriate transformations, all the
      demographic and socioeconomic variables selected have statistically significant
      and direct influence on infant death.

PMID- 9584577
TI  - A dynamic, multi-level analysis of recent immunization trends in Colombia.
AB  - During 1985-91, Latin American ministries of health carried out the ultimately
      successful Regional Polio Eradication Initiative. Unprecedented vaccine coverage
      levels were attained through a combination of mass campaigns, house-to-house
      vaccinations, and improvements in routine immunization services. Little is known,
      however, about the effects of these interventions on immunization demand; whether
      they reached so-called high-risk households and, if so, whether program effects
      were sufficient to offset the household risk factors. This paper examines the
      probability and timing of full immunization over this period in one case country,
      Colombia. Information on the immunization status of 3,609 vaccine-eligible
      children born 1985-90 was extracted from Colombia's 1990 Demographic and Health
      Survey. Annual immunization coverage estimates from the Colombian Ministry of
      Health for 1985-90 for 148 sample municipios were appended to each child record,
      along with household-level data. Initial non-parametric regressions showed that
      five of six observed risk factors negatively influenced full immunization
      probability. Multivariate logit models showed that parents who had already lost a
      child were significantly less likely to obtain immunization cards (a proxy for
      exposure to the routine immunization program), despite rising cardholdership
      rates over the period. Among 1,376 immunization cardholders, waiting times to
      full immunization fell monotonically over the period. Local program coverage of
      80 per cent or higher and prior use of prenatal services both increased the
      probability of full immunization. However, three of five maternal occupational
      categories decreased the probability, as did three of six observed household risk
      factors. The results show that demand for routine immunizations rose over the
      period, that only the highest-risk households were not exposed to the routine
      program, and that routine program participation partially offset negative risk
      factor effects on the probability of full immunization. While targeted PHC
      interventions may increase health production by recruiting high-risk households
      into the routine PHC services, further health production increases will require
      more intensive follow-up of such households through routine PHC services.

PMID- 9584579
TI  - Postpartum amenorrhoea in Ethiopia: the role of weaning, child death, and
      socioeconomic factors.
AB  - Using data from the 1990 National Family and Fertility Survey (NFFS) and
      employing discrete-time hazards models, we examine the effect of weaning, child
      death, and socioeconomic factors on postpartum amenorrhoea in Ethiopia. The
      results show that 91 in every 100 mothers breastfed their child for at least 6
      months. The median duration of breastfeeding stands at 18 months, and amenorrhoea
      lasts for a median duration of 12 months. Significant variations in breastfeeding
      and amenorrhoea duration are also observed among the different categories of
      breastfeeding women. The median duration of breastfeeding for lactating women is
      24 months, 6 months for those who weaned, and 2 months for those whose child
      died. The median duration of postpartum amenorrhoea is 14 months for
      breastfeeding women, 12 months for those who weaned, and 6 months for those whose
      child died. Discrete-time hazard models reveal that child death has the strongest
      effect on the resumption of menses. Net of other factors, the risk of returning
      to menses increased 3 times for mothers whose child died. The effect of child
      death, however, decreases over time. Weaning also has a significant positive
      effect; and, like child death, its effect diminishes as time passes. The study
      further shows significant differences in the risk of returning to postpartum
      menses by socioeconomic characteristics of the women, even though they are
      breastfeeding.

PMID- 9584578
TI  - Economic security, informational resources, and women's reproductive choices in
      urban Mozambique.
AB  - Reproductive changes in sub-Saharan Africa are contingent upon women's
      socioeconomic conditions and informational and cultural resources. This study
      focuses on socioeconomic and cultural determinants and correlates of the
      intention to stop childbearing and of contraceptive use among urban women in
      Mozambique. It uses data from a survey of 1,585 married women conducted in
      Greater Maputo in 1993, and it employs logistic regression for multivariate
      analysis. The results of the analysis indicate that although the stopping
      intention and contraceptive use are interrelated and similarly affected by such
      factors as education or the area of residence, the intention to stop childbearing
      is mainly driven by women's perception of their material conditions and
      socioeconomic security, while contraceptive use is largely a product of social
      diffusion and the legitimization of innovative, Western-origin information and
      technologies. The study proposes that these findings may help explain the unique
      features of the fertility transition in sub-Saharan Africa.

PMID- 9584580
TI  - Third birth intentions and uncertainty in Canada.
AB  - Using data from the 1995 Canadian General Society Survey (GSS-95), we study the
      intention to have a third child among a sample of women and men who have already
      had two children (N = 505). Our results show that 15 per cent of the respondents
      intend to have a third child. Nearly 20 per cent of the respondents are uncertain
      about their fertility intentions. We found that the same factors that predict
      intentions also predict uncertainty, and that the effects of these predictors are
      remarkably similar. In particular, intentions and uncertainty generally decline
      with age, but increase with regular church attendance, remarriage, and being
      Catholic. Unlike earlier studies, we found that the sex of previous children has
      virtually no impact on third-birth intentions or uncertainty.

PMID- 9584581
TI  - Socioeconomic status and use of family planning among Ghanaian government
      workers.
AB  - The low utilization of family planning methods in Ghana, and by inference in much
      of Africa, is explained by reference to traditional sociocultural values held by
      males. A LISREL model is tested using data collected from educated males working
      in the Ghanaian government. Among the findings are that lack of couple
      communication, segregated conjugal role relationships, and male-dominated
      decision-making are all significant predictors of non-use of family planning
      methods (pronatalist attitude is not). Possession of knowledge of family planning
      among Ghanaian males alone is unlikely to initiate use of family planning
      methods. Additional sociodemographic and modernization findings are reported.

PMID- 9584582
TI  - Behavioral contagion and official delinquency: epidemic course in adolescence.
AB  - The cumulative onset curves for smoking, drinking, and sexual intercourse have
      been tracked through adolescence with reasonable success by recursive equations
      positing an "epidemic" or contagious process. The gist of these models is that
      the likelihood of onset in the next time period is proportional to the prevalence
      of the behavior among an adolescent's peers in the current time period. The
      present paper extends this approach to official delinquency. The fits to the data
      (from the Philadelphia cohort studies) are extremely tight. Several conceptual
      mismatches between the theory underlying the model and the model itself are
      discussed.

PMID- 9584583
TI  - Conditions at conception in women with recurrent miscarriage.
AB  - In order to evaluate the role of conditions at conception in the risk of
      miscarriage, we sent 234 women with at least two consecutive miscarriages after
      conceptions from the same partner a short questionnaire asking for the birth
      dates of their mothers and their live or stillborn siblings and the occurrence of
      any maternal miscarriages. Complete information was provided by 186 respondents.
      Using matched logistic regression, we investigated whether these women were born
      more often than their siblings (total n = 578) to young (< or = 19 years) or
      relatively old (> or = 40 years) mothers or shortly after a preceding pregnancy
      (born within 1 year). We also evaluated whether they showed a different month-of
      birth distribution. No increased odds ratios were found for young or advanced
      maternal age, or for short preceding birth intervals. However, relative to their
      siblings, cases showed a deviant month-of-birth distribution (p = 0.08) with a
      peak in (late) winter. These results indicate that low and high maternal age and
      short preceding birth intervals are not determinants of the risk of miscarriage
      in the daughter. They also suggest that there may be seasonally varying factors
      that prenatally influence the risk of miscarriage.

PMID- 9584584
TI  - [The organization of dental care for the population and the prospects for its
      development under the new economic conditions].

PMID- 9584585
TI  - [The prospects for the development of prophylactic dental programs in Russia (a
      historical and situational analysis)].

PMID- 9584586
TI  - [The action of Carpule-delivered local anesthetics and their combinations with
      vasoconstrictors].
AB  - Analysis of published data on the effects of drugs used in dentistry for local
      analgesia and of the authors' findings will help the dentists properly select
      adequate analgesia with due consideration for the extent of intervention and
      patient's condition. Study of carpulated local amide anesthetics lidocaine,
      mepivacaine, and articaine revealed the relationship between the efficacy of
      anesthesia and its effects on cardiovascular system, on the one hand, and the
      anesthetic proper, presence of a vasoconstrictor, and type of anesthesia, on the
      other.

PMID- 9584587
TI  - [The microcirculation in periodontal tissues: 2. The action of the regular use of
      chewing gum].
AB  - The effect of regular use of chewing gum (for 28 days) on microcirculation was
      assessed in 35 patients with slight and medium-severe periodontitis by
      biomicroscopy and laser Doppler flowmetry. Microcirculation normalized
      immediately after chewing training due to arrest of arteriolar spasm. In slight
      periodontitis the effect persists for almost one year, in medium-severe condition
      for up to 6 months, because of more expressed structural changes in the
      microvessels of periodontal tissue.

PMID- 9584588
TI  - [The determination of the extent of a surgical intervention on periodontal
      tissues].
AB  - A surgical intervention is needed in patients with periodontal pouches deeper
      than 4-5 mm. The results of 239 operations in 182 patients are analyzed. Optimal
      variants of the operations are described, depending on the patient's status,
      analgesia, types of secondary adentia, surgical access, and intervals between the
      operations.

PMID- 9584589
TI  - [Validation of the use of corsodyl in the combined treatment of periodontitis].

PMID- 9584590
TI  - [The combined treatment of patients with progressive phlegmons of the
      maxillofacial area].
AB  - Based on assessment of the severity of endogenous intoxication, the authors
      developed a complex differentiated protocol for the treatment of patients with
      phlegmons of the face and neck, including electrochemical detoxication and
      intravenous laser exposure of the blood. Such treatment appreciably decreases
      endogenous intoxication, normalizes homeostasis, more rapidly arrests local
      pyoinflammatory process, and thus cuts down the duration of treatment and
      improves its outcomes.

PMID- 9584591
TI  - [The clinical value of determining erythrocyte sorption capacity and the levels
      of middle molecules and circulating immune complexes in assessing endotoxemia in
      patients with abscesses and phlegmons of the maxillofacial area].
AB  - The intoxication degree in abscesses and phlegmons of maxillofacial area may be
      extremely variable and connected with the microflora type, the patient's age and
      reactivity of the organism. We believe that the most promising markers of
      endogenous intoxication are the indices of sorption ability of erythrocytes,
      medium-weight molecule level and circulating immune complexes.

PMID- 9584593
TI  - [The x-ray characteristics of the visceral cranium in children with branchial
      arch syndromes I and II].
AB  - X-ray changes in the skull bones of children and adolescents with the first
      second branchial arches syndrome are analyzed. Roentgenograms and sonograms of
      various parts of the skull of 66 patients are analyzed. The syndrome involves
      underdevelopment of half of the mandible and the condylar process and changes in
      the bones of the median zone of the face, temporal bone, base of the skull, and
      nasal cavity. The patients were divided into 3 groups with different degrees of
      mandibular deformations, requiring different treatment strategies.

PMID- 9584592
TI  - [The pathogenesis of combined maxillocerebral trauma].
AB  - Study of the systemic and regional blood pressure in various parts of the
      maxillofacial area and of microcirculation in tissues and fundus oculi in
      patients with maxillofacial injuries showed that such traumas involve brain
      injuries in 100% of cases and are therefore combined. The authors emphasize that
      this patient population is to be treated for brain injuries.

PMID- 9584594
TI  - [The nonspecific resistance of the oral cavity in preschool children during the
      prevention of dental caries with fluoridated salt].
AB  - Nonspecific resistance of the oral cavity was studied from microorganism
      adsorption in children using fluorinated table salt for the prevention of dental
      caries. Epitheliocytes with a high adsorption capacity were detected in smears
      from preschool children using fluorinated salt for 2 and 3 years 1.5 and 1.6
      times more often, respectively, than in those using common salt. Nonspecific
      resistance of the oral cavity of preschool children whose ration included
      fluorinated salt for 2 and 3 years was considered good in 95.1 +/- 2.15% and 100%
      of cases, respectively, as against 62.57 +/- 7.67% in children not included in
      the prophylactic program.

PMID- 9584596
TI  - [Physical factors in the combined rehabilitation of children with a congenital
      cleft of the upper lip].
AB  - A total of 551 children with cleft lips and 136 children with secondary
      deformations of the upper lip and nose were followed up after cheiloplasty.
      Electrostimulation of the upper lip, total UV exposure, humisol and pelloidine
      electrophoresis, and total massage before cheiloplasty decreased the incidence of
      general and local postoperative complications. Reconstructive cheiloplasty was
      preceded by lidase or iodine ultraphonophoresis or electrostimulation of the
      perioral muscles. After surgery a course of magnetic and laser exposure or
      heparin ultraphonophoresis and local troxevasin were prescribed. This improved
      both the cosmetic and functional result of the operation.

PMID- 9584595
TI  - [Ways to improve the caries resistance of the temporary teeth by using
      fluoridated salt].
AB  - The content of calcium and phosphorus is decreased and that of fluorine increased
      in the oral fluid of children whose diet includes fluorinated salt, and the
      levels of calcium and phosphorus in their dental enamel are increased in
      comparison with children using common table salt. Three-year consumption of
      fluorinated salt resulted in a decrease of calcium release and increase of
      phosphorus release into acid biopsy.

PMID- 9584597
TI  - [A method for preventing and treating maxillodental anomalies related to
      disordered nose breathing].
AB  - Eleven children aged 5-9 years with maxillodental abnormalities were treated
      using positioners. Negative effects of positioners and activators (increase of
      dental caries, hygienic index, and acid resistance of the enamel) are analyzed.

PMID- 9584598
TI  - [Planning the scope, time and costs of orthodontic treatment in relation to the
      degree of its complexity].

PMID- 9584599
TI  - [Experience in conducting lecture series in advanced training for dentists and
      dental technicians at the work sites in polyclinics].
AB  - A system of postgraduate training of dentists and dental technologists is
      proposed. Its basic part is general training, improving the qualification
      category of these specialists. The traditional form of organization of the
      training process remains unchanged.

PMID- 9584601
TI  - [The Stomatology Information Retrieval (Reference) System].
AB  - The structure and functions of the "Stomatology" information and search (inquiry)
      system are described. The system includes data on the designers, certifiers, and
      distributors of equipment for dentistry, therapeutic and training institutions,
      Ministry of Health, All-Russian Association of Stomatologists, Central Research
      Institute of Dentistry, editorial boards of journals in dentistry, and their
      relationship through the Mednet federal public health network.

PMID- 9584600
TI  - [Experience in conducting course exams in test form].
AB  - Examinations including tasks presented as tests were carried out in 319 fourth
      year students of dental surgery. This method for assessing the knowledge and
      skills of students proved to be highly objective.

PMID- 9584603
TI  - Health care report cards: what grade do they get?

PMID- 9584604
TI  - Old past history critical.

PMID- 9584605
TI  - The natural history of Pap test screening in a rural population.

PMID- 9584606
TI  - Meningoencephalitis: an atypical presentation of herpes simplex type 2 central
      nervous system infection.
AB  - Encephalitis is the best recognized form of central nervous system (CNS)
      infection with the herpes simplex virus. We present a case of meningoencephalitis
      with a benign course caused by herpes simplex virus type 2. The patient had no
      focal abnormalities on either brain magnetic resonance imaging scan or
      electroencephalogram. The cerebrospinal fluid profile was that of aseptic
      meningitis, with a lymphocytic pleocytosis. The clinical spectrum of herpes
      simplex infections in the CNS is broad. Specifically, herpes simplex type 2 can
      cause a benign meningoencephalitis with scant focal findings, in addition to the
      known encephalitis and more recently recognized benign recurrent lymphocytic
      meningitis.

PMID- 9584607
TI  - Adult-onset Still's disease.

PMID- 9584608
TI  - Acute cytomegalovirus hepatitis with systemic lupus erythematosis.

PMID- 9584609
TI  - Diabetes control in Tennessee.

PMID- 9584610
TI  - Multi-ligand interactions with receptor-like protein tyrosine phosphatase beta:
      implications for intercellular signaling.
AB  - Receptor-like protein tyrosine phosphatase beta (RPTP beta) shows structural and
      functional similarity to cell adhesion molecules (CAMs). It binds to several
      neuronal CAMs and extracellular matrix (ECM) proteins that combine to form cell
      recognition complexes. Here, the authors discuss the implications of such
      complexes for intercellular signaling, and the regulation of RPTP activity by
      cell-cell and cell-ECM contact.

PMID- 9584611
TI  - Sense and nonsense DNA.

PMID- 9584612
TI  - Not so peculiar: fission yeast telomere repeats.

PMID- 9584613
TI  - The catalytic domain of the P-type ATPase has the haloacid dehalogenase fold.

PMID- 9584614
TI  - Conserved structural motifs in the sulfotransferase family.

PMID- 9584615
TI  - Molecular mechanisms of yeast aging.
AB  - The life cycle of many organisms involves a progressive decline in fitness and
      fecundity with age, and yeast is no exception. Many theories have been proposed
      to explain the mortality of yeast cells, including the increase in cell size and
      accumulation of bud scars on the cell surface. None of these has survived closed
      scrutiny. However, recent discoveries might have validated one aging model in
      which the triggering of a molecular aging clock results in the replication and
      accumulation of a senescence factor that eventually overwhelms old cells.

PMID- 9584616
TI  - Iron and copper transport in yeast and its relevance to human disease.
AB  - Recent progress in the field of copper and iron metabolism has resulted from a
      convergence of human and yeast genetics. The mechanisms of iron and copper
      transport are remarkably conserved between yeast and humans. Studies of the yeast
      homologs of human disease genes involved in metal homeostasis have shed light on
      the pathophysiology of these disorders.

PMID- 9584617
TI  - The ins and outs of a molecular chaperone machine.
AB  - Genetic and biochemical work has highlighted the biological importance of the
      GroEL/GroES (Hsp60/Hsp10; cpn60/cpn10) chaperone machine in protein folding.
      GroEL's donut-shaped structure has attracted the attention of structural
      biologists because of its elegance as well as the secrets (substrates) it can
      hide. The recent determination of the GroES and GroEL/GroES structures provides a
      glimpse of their plasticity, revealing dramatic conformational changes that point
      to an elaborate mechanism, coupling ATP hydrolysis to substrate release by GroEL.

PMID- 9584618
TI  - Responses of E. coli to osmotic stress: large changes in amounts of cytoplasmic
      solutes and water.
AB  - Escherichia coli is capable of growing in environments ranging from very dilute
      aqueous solutions of essential nutrients to media containing molar concentrations
      of salts or nonelectrolyte solutes. Growth in environments with such a wide range
      (at least 100-fold) of osmolarities poses significant physiological challenges
      for cells. To meet these challenges, E. coli adjusts a wide range of cytoplasmic
      solution variables, including the cytoplasmic amounts both of water and of
      charged and uncharged solutes.

PMID- 9584619
TI  - CLAMP: a biosensor kinetic data analysis program.

PMID- 9584620
TI  - Light on a dark lady.

PMID- 9584621
TI  - Dizocilpine (MK801): use or abuse?

PMID- 9584622
TI  - Cytochrome P450 in the brain: 2B or not 2B.

PMID- 9584623
TI  - Three-state and two-state models.

PMID- 9584624
TI  - G protein-coupled-receptor cross-talk: the fine-tuning of multiple receptor
      signalling pathways.
AB  - Signalling via the large family of G protein-coupled receptors (GPCRs) can lead
      to many cellular responses, ranging from regulation of intracellular levels of
      cAMP to stimulation of gene transcription. Members of this receptor family have
      been grouped into different categories dependent on the particular G protein
      subtypes that they predominantly interact with. Thus, receptors that couple to GS
      proteins will stimulate adenylate cyclase in many cells, while Gq/11-coupled
      receptors can mobilize intracellular Ca2+ via activation of phospholipase C.
      There is accumulating evidence, however, that activation of one particular
      signalling pathway by a GPCR can amplify intracellular signalling within a
      parallel but separate pathway. In this article Lisa Selbie and Stephen Hill
      review some of the evidence for these synergistic interactions and suggest that
      they may have an important role in finetuning signals from multiple receptor
      signalling pathways.

PMID- 9584625
TI  - mu-Opposing actions of the kappa-opioid receptor.
AB  - Pharmacological studies and recent research using genetic approaches have
      indicated that most actions of exogenous opioids, such as morphine, are mediated
      through the mu-opioid receptor. By contrast, the function of the kappa-opioid
      receptor in opioid actions largely remains unclear. In this article, Zhizhong Z.
      Pan discusses the accumulating evidence that activation of the kappa-receptor
      antagonizes various mu-receptor-mediated actions in the brain, including
      analgesia, tolerance, reward and memory processes. The neural mechanism for this
      potentially ubiquitous mu-opposing function of the kappa-receptor is believed to
      involve distinct locations of the two opioid receptors on physiologically
      different cell types in local neuronal networks that are implicated in an opioid
      action.

PMID- 9584626
TI  - The regulation of vascular function by P2 receptors: multiple sites and multiple
      receptors.
AB  - Although the effects of nucleotides in the cardiovascular system have been known
      for almost 70 years, it is only in the past few years that some of the P2
      receptors at which they act have been cloned and characterized. It is now clear
      that the control of cardiovascular function by nucleotides is complex, involving
      multiple receptors and multiple effects in the different cell types of
      importance. In this review Mike Boarder and Susanna Hourani summarize the P2
      receptors that are present in endothelial cells, platelets, smooth muscle and
      nerves, the signalling pathways that they activate and the responses that are
      produced. They also discuss the important role of nucleotides in the interactions
      between the different cell types, and the implications of this in vascular
      disease.

PMID- 9584627
TI  - Structural basis of drug binding to L Ca2+ channels.
AB  - At least five different types of voltage-gated Ca2+ channels exist in
      electrically excitable mammalian cells. Only one type, the family of L-type Ca2+
      channels (L channels), contains high-affinity binding domains within their alpha
      1-subunits for different chemical classes of drugs (Ca2+ channel antagonists;
      exemplified by isradipine, verapamil and diltiazem). Their stereoselective, high
      affinity binding induces block of channel-mediated Ca2+ inward currents in heart
      and smooth muscle, resulting in antihypertensive, cardiodepressive and
      antiarrhythmic effects. Amino acids involved in drug binding have recently been
      identified using photoaffinity labelling, chimeric alpha 1-subunits and site
      directed mutagenesis. Insertion of the drug-binding amino acids enabled the
      transfer of drug-sensitivity into Ca2+ channels that are insensitive to Ca2+
      channel antagonists ('gain-of-function' approach). In this review, Jorg
      Striessing and colleagues summarize the present knowledge about the molecular
      architecture of L channel drug-binding domains and the implications for Ca2+
      channel pharmacology and drug development.

PMID- 9584628
TI  - [Methods for screening the visual field for glaucoma].
AB  - The methods used for screening the visual field for glaucoma are not devoid of
      shortcomings, for their results can be false-positive as regards scotoma. Their
      advantages are not disputed. The methods we propose can rapidly detect not only
      disorders in the visual field, but assess them quantitatively in the area of
      special interest for the physician, specifically, in the Bjerrum area in
      screening for glaucoma. Although the results of screening perimetry are just
      tentative, it is desirable to assess the depth of optic sensitivity loss in
      decibells during such examinations. Static variants of screening perimetry,
      including that under conditions of loading tests (e.g. vacuum perimetry) acquire
      more and more significance in clinical and preclinical studies.

PMID- 9584629
TI  - [Efficacy and safety of timoptic depot in hypotensive therapy of glaucoma].
AB  - The efficacy of timoptic depot is assessed in 20 patients with open-angle
      glaucoma, previously treated with 0.25 and 0.5% timolol. Instillations of 0.25
      and 0.5% timoptic depot for 4 weeks did not appreciably change the intraocular
      pressure, no local or general side effects were noted. Hence, timoptic depot is a
      more convenient drug for glaucoma patients, remaining effective even after long
      use.

PMID- 9584631
TI  - [Effects of surgical wounds hermetic closure methods in cataract extraction on
      postoperative corneal astigmatism].
AB  - Main factors of hermetic closure of the operation wound after cataract extraction
      are discussed. A new method of closing the wound in this operation is described.
      The opposition intracorneal mattress sutures are made across the section plane.
      Their principal difference is that the thread is not thrown over the external
      edge of the section of the cornea, as in traditional suturing, and when pulled
      tight, the thread does not deform the external surface of the cornea in the
      central zone, and thus does not induce postoperative astigmatism. Eighteen
      patients were operated on using this technique. Opposition sutures made after the
      above technique involve no high postoperative astigmatism or none at all.

PMID- 9584630
TI  - [Permeability of blood-aqueous humor barrier in primary open-angle glaucoma].
AB  - Biochemical changes in the chamber humor play an important role in the
      pathogenesis of primary open-angle glaucoma and are largely determined by the
      permeability of the blood-eye barrier. Comparative study of total protein content
      in the chamber humor in mature and far advanced glaucoma showed that the disease
      involves a progressive increase in the permeability of the blood-aqueous humor
      barrier, which may be due to dystrophic changes in ocular tissues in the course
      of glaucoma progress and accumulation of metabolites damaging the biological
      membranes in the chamber fluid or to antiglaucoma drugs increasing the
      permeability of the blood-humor barrier.

PMID- 9584633
TI  - [Metastatic involvement of liver in patients with uveal melanoma].
AB  - The efficacy of enucleation and brachitherapy is assessed in 1150 patients. The
      incidence of metastases is the highest (up to 2/3) occurs within the first 3
      years. Neither enucleation, nor brachitherapy affect this value. However, in
      general after enucleation the incidence of metastases to the liver (31.7%) is
      higher than after brachitherapy (5.8%), this indicating that brachitherapy is
      more effective in minor and medium-sized melanomas of the choroid.

PMID- 9584632
TI  - [Impact of focal allergic test with herpetic vaccine in diagnosis of ophthalmic
      herpes].
AB  - Clinical and immunological studies were carried out in 697 patients (913 eyes)
      for a more accurate diagnosis of herpetic involvement of the posterior segment of
      the eye by the focal allergic test (FAT) based on the delayed type
      hypersensitivity phenomenon. FAT consists in detection of the focal reaction in
      the eye, regularly developing after 2-3 intracutaneous injections of herpetic
      vaccine to types I and II herpes simplex virus in a dose of 0.2 ml every other
      day. The reaction is assessed by clinical and functional methods: visometry,
      campimetry, biomicroscopy, 9-point test, Amsler network, Hedinger's phenomenon,
      photocolor stress test, Rabkin's polychromatic tables, fluorescent angiography of
      the fundus oculi, electrophysiological methods, critical frequency of flash
      fusion, reflection microscopy of the corneal endothelium, and color campimetry
      realized on an IBM-compatible computer before and after vaccination of patients
      with suspected herpetic involvement of the eye. FAT was positive in 395 (56.6%)
      patients in 568 (62.2%) eyes. Examination of the threshold relative brightness
      sensitivity before and after FAT revealed positive results in 70% of patients.
      FAT is an accurate non-invasive method for the diagnosis of various
      manifestations of intraocular herpes. Relative safety of FAT recommends it for
      clinical practice to be used in the diagnosis of herpetic involvement of the
      posterior segment of the eye.

PMID- 9584634
TI  - [Optimal terms of patients rehabilitation with eye injuries].
AB  - Studies of the immune status and biochemical composition of the anterior chamber
      humor and blood plasma in 216 patients with various injuries to the eye in
      different periods after the trauma and clinical data helped the author determine
      the optimal terms of rehabilitative treatment of this patient population,
      depending on the type of injury.

PMID- 9584635
TI  - [Clinical etiological analysis of infective penetrating wounds of eyes in
      children].
AB  - Clinical laboratory analysis of penetrating wounds of the eyes in children in
      1990-1995 showed a tendency to an increase in the incidence of wound infection,
      which increased as high as to make 16.6%. Opportunistic bacteria predominated in
      the etiological structure of wound infection agents. They caused grave
      suppurative complications in the presence of decreased antibacterial resistance
      of the organism.

PMID- 9584636
TI  - [Hemocomponent therapy of central involution chorioretinal dystrophy].
AB  - Hemocomponent therapy was used in 181 patients (347 eyes) with central
      chorioretinal dystrophy. Activated autoplasma possessing a marked resorptive
      effect, consisting in resorption of hemorrhages and exudations on the fundus
      oculi, was used. Vision acuity improved in 75% of examined eyes by an average of
      0.2 diopters.

PMID- 9584637
TI  - [Antioxidant therapy of vision organ disorders in the Chernobyl accident
      liquidators].
AB  - Antioxidant complex including flacumine, glutamic acid, and sodium thiosulfate
      was used to treat pathological changes in the organ of vision in the liquidators
      of the Chernobyl accident. The treatment stabilized vision acuity and improved
      some hormonal and immunological parameters of the blood. Hence, this therapeutic
      complex can be used for the prevention and treatment of ocular abnormalities in
      subjects exposed to radionuclides.

PMID- 9584638
TI  - [New method of visual fields color division in diploptic treatment of
      strabismus].
AB  - A new method of color division of the visual fields based on polarized light
      interference is described. A new method for diploptic therapy of strabismus is
      developed, based on the above principle and possessing numerous advantages. The
      method was used in 38 patients with binocular disorders of various severity;
      binocular function improved in 18. The method is particularly effective in the
      patients with correct position of the eyes with bifoveal fusion on the
      synaptophore and parallel color test vision and in the patients with binocular
      vision and amblyobinopia.

PMID- 9584639
TI  - [Use of complex compression diagnostic test for defining the indications for
      surgical treatment of atherosclerotic chorioretinal dystrophy].
AB  - Complex compression diagnostic test was carried out in 38 patients (72 eyes) with
      atherosclerotic maculodystrophy in order to define the indications for and
      predict the results of treatment by direct laser phoresis. The results of the
      test were assessed for 4 parameters: vision acuity, critical frequency of fusion
      of flashes, visocontrastometry, and rheography. The preoperative values did not
      reliably differ from the postoperative ones. Complex compression test can be used
      to predict the results of surgery for atherosclerotic maculodystrophies aimed at
      improving the hemodynamics and microcirculation in the posterior compartment of
      the eye.

PMID- 9584640
TI  - [Pharmacokinetics of recombinant pro-urokinase ocular dosage form].
AB  - Thrombolytic enzymes are widely used in the treatment of vascular diseases of the
      eyes and of intraocular hemorrhages. We studied the pharmacokinetics of
      recombinant prourokinase (proRUK) in ocular structures after its intravitreal
      administration and subtenon's implantation of collagen infusion system (SICIS).
      Kinetic parameters of accumulation of labeled proRUK in ocular structures were
      obtained. After intravitreal administration, the proRUK half-life (T1/2) was 7.9
      +/- 1.44 h, with proRUK losing none of its enzymatic activity while in the
      vitreous body. The maximum accumulation of proRUK in the vitreous administered by
      the SICIS is observed after 4-5 h and is 1.5-2.0% of the dose administered. In
      the sclera the maximum accumulation of proRUK is 10-15% (4-6 h after
      administration), in the vascular membrane 0.8% (4 h after administration). We
      believe that combination of intravitreal and SICIS-aided administration of proRUK
      to patients with extensive hemorrhages (subtotal and total hemopthalmia) will
      improve the efficacy of therapy.

PMID- 9584641
TI  - [Natural cytokine complex as a drug bioregulator in healing of alkaline burns of
      cornea (experimental morphological study)].
AB  - Clinical morphological features of reparative processes of alkaline burns of the
      cornea are studied in 24 rabbits. Effects of the natural cytokine complex on this
      process are validated. Burn process is regarded as an immune inflammation.
      Morphological and morphometric data demonstrate the mechanism of the cytokine
      effect on the reparative processes in the cornea, based on the regulation of the
      inflammatory postburn and proliferative processes. The repair of the cornea after
      burn in experiment and control is described in detail.

PMID- 9584642
TI  - [Systemic and local immunity in patients with diabetic retinopathy].
AB  - Total-systems and local immunity parameters were assessed in the lacrimal fluid
      of 118 patients with nonproliferative and proliferative diabetic retinopathy
      (DR). Humoral and cellular immunity characteristics of the total-systems immunity
      were shifted and local immune homeostasis impaired. The most manifest changes
      were detected in patients with proliferative DR. The authors hypothesize a
      possible contribution of local immune disorders to the pathogenesis of DR.

PMID- 9584643
TI  - [Contact correction: method for arresting the progress of keratoconus].
AB  - The effect of rigid contact lenses on the course of keratocone during different
      stages is studied. A total of 121 patients (234 eyes) aged 11 to 49 years were
      examined. Early onset of keratocone is associated with its more rapid progress;
      the evolution of the disease from the initial to terminal stage takes 7 years
      with lenses and 4 without them; the progress of keratocone from one stage to
      another with contact correction takes more than 2 years versus less than 1.5
      years without correction. Rigid contact lenses inhibit the progress of keratocone
      only at the initial stage of the disease.

PMID- 9584644
TI  - [Cataract extraction in a patient with sympathetic uveitis after immunity
      correcting therapy].
AB  - A complicated cataract on the only eye was effectively extracted in a patient
      with uveitis running a sluggish course with manifest disorders of T-cell
      immunity. Immune correction in combination with routine therapy of uveitis helped
      prepare the patient to surgery for cataract and attain good results.

PMID- 9584645
TI  - [Current problems of keratoplasty in children].

PMID- 9584646
TI  - [Single-photon emission-computed tomography in evaluation of cerebral
      microcirculation of patients with epileptiform syndrome].
AB  - One-photon emission computed tomography (OPECT) was used to examine 87 patients
      with the epileptiform syndrome. Eighty five patients had impaired drug
      distribution which was suggestive of varying degree cerebral circulatory
      disorders. OPECT with a Tc-99m-gm-pao used in patients with the epileptiform
      syndrome revealed the morphological substract of brain structures. OPECT findings
      in the patients suggested the brain structural microcirculatory changes to be
      diffuse and focal, of varying magnitude. There was no clear correlation between
      clinical manifestations and OPECT and CT findings.

PMID- 9584647
TI  - [Radiation diagnosis of cerebellar and fourth ventricle tumors].
AB  - Thirty four patients with tumors of the cerebellum and the fourth ventricle were
      examined. All the patients underwent craniography and computed tomography (CT),
      28 had magnetic resonance imaging (MRI). According to the histological pattern,
      the tumors were divided as follows: astrocytomas in 14 patients,
      hemangioblastomas in 8, ependymomas of the fourth ventricle in 5,
      medulloblastomas in 3, choriopapillomas in 2, two patients were found to have
      metastases. MRI was shown to be the most informative technique in the diagnosis
      of bulky abnormal formations of the cerebellum and the fourth ventricle of the
      cerebrum. The maximum degree of contrast between normal and damaged tissue
      provides evidence for correctly establishing a tumor, determining its outlines,
      and relation to the brain stem and cerebrospinal system. The use of different
      pulse sequences with MRI makes it possible to have a more valid differential
      diagnosis. Computed tomography is an additional technique in examining patients
      with tumors of the cerebellum and the fourth ventricle to obtain data on the
      plain characteristics of an abnormal focus and their changes after intravenous
      reinforcement. The application of a complex of radiation studies leads to the
      conclusion that the bulky abnormal formations of the cerebellum and the fourth
      ventricle are likely to be morphologic.

PMID- 9584648
TI  - [Clinical and X-ray manifestations of pulmonary tuberculosis predominantly
      involving bronchi].
AB  - In 15.8% of the patients with pulmonary tuberculosis who had been admitted to the
      Clinic, the bronchial tree was the leading site of an infectious process.
      Complicated bronchial tuberculosis involving other structures of the organ was
      revealed in nearly all cases, which led to its misinterpretation as focal,
      infiltrative, cirrhotic tuberculosis and pulmonary tuberculoma. The understanding
      of clinical and X-ray variants of its course, and the physician's skills in using
      X-ray anatomic and clinical and bronchological findings are useful in correctly
      diagnosing bronchial tuberculosis.

PMID- 9584649
TI  - [Low-dose digital radiography in diagnosis of stomach and duodenal cancer and
      peptic ulcer].
AB  - While analyzing data of 149 studies of the stomach and duodenum, covering
      patients with gastric cancer (n = 66), peptic ulcer (n = 41) versus 42
      individuals without abnormalities by means of a STs3 digital device, the authors
      express their opinion on some aspects of the gastroenterological application of
      digital roentgenology. To evaluate the potentialities of recording all details,
      revealed changes on the standard writing paper by digital roentgenology is a main
      area of the study. For this, the data of the 149 studies were used to compare the
      informative value of the obtained image on the X-ray film and writing paper. In
      the author's opinion, digital roentgenology completely rules out the application
      of an X-ray film, by replacing it by standard writing paper.

PMID- 9584650
TI  - [Magnetic resonance imaging in the diagnosis of spinal injuries].
AB  - Magnetic resonance imaging reveals the morphological changes of the spinal cord
      in the early and late periods following vertebral and spinal cord injuries. Edema
      frequently accompanied by squeezing and displacement of the spinal cord by the
      elements of broken vertebrae and disks, which are dislocated into the lumen of
      the spinal canal is the most common change in the early period. In the late
      period, there is myelomalacia that progresses to cerebrospinal cyst. End-stage
      injury is characterized by spinal atrophy, intra- and extramedullar cerebrospinal
      cysts and cicatricial and adhesive changes in the spinal canal.

PMID- 9584651
TI  - [Clinical and X-ray diagnosis of vertical blood reflux in muscle-venous pump of
      lower extremities and pelvis in varicosity].
AB  - Four hundred and twenty three patients with varicosity were comprehensively
      examined and surgically treated. X-ray diagnosis of vertical blood reflux was
      made in each of 4 musculovenous pumps (the abdominocaval pump, the punps of the
      hip, shin, foot). The first pump was studied by retrograde pelvic phlebography
      through the contralateral leg, the second one was examined by retrograde contrast
      administration into the onset of the external iliac vein as the second stage of
      retrograde pelvic phlebography or by its direct puncture, the third pump was
      explored by retrograde saphenous phlebography with pneumocompression of deep
      veins of the hip proximalo the site of puncture. The vertical reflux in the foot
      pump was determined by retrograde talocrural phlebography by contrast
      administration into the accompanying rectal vein above 4 cm of the foot along the
      Lington line. At surgery, vertical blood reflux was removed in each area of the
      musculovenous pump by extravasal correction of failing deep venous valves.
      Analyzing the outcomes of treatment in the patients and controls who underwent
      routine superficial and accompanying vein surgery without removing vertical blood
      reflux showed that the application of the new approaches to X-ray diagnosis and
      treatment of varicosity yielded excellent and good treatment outcomes by 10.6%,
      reduced poor ones by 10.8%, shortened the mean disability duration by 15.6 + 2.3
      days, prevented disability.

PMID- 9584652
TI  - [Evaluating the efficiency of combined and radiation treatment of vulvar cancer].
AB  - The outcomes of radiation treatment of 70 patients with Stage I-II vulvar cancer
      are analyzed. Combined treatment was used in 10 patients (3 and 7 patients had
      Stage I and II, respectively), combined radical radiation therapy was applied in
      21 patients (Stage II), split-course gamma-teletherapy was employed in 28
      patients (6 and 22 patients with Stages II and III, respectively) and 3 females
      had short-range X-ray therapy. Palliative radiation therapy was performed in 8
      patients with Stage III tumors. Complete clinical tumor resolution was achieved
      in 16 (57%) patients receiving gamma-teletherapy, 15 (71.4%) and in all three
      women having short-range X-ray therapy. It is recommended that patients with
      vulvar cancer should receive split-course radiation, which yields good late
      treatment results and prevents from significant local radiation reactions and
      complications. Early diagnosis and timely use of combined treatment provide best
      treatment results in patients with vulvar cancer and in those with other
      malignant neoplasms.

PMID- 9584653
TI  - [On X-ray diagnosis of some inferior vena cava developmental malformations].

PMID- 9584654
TI  - [Osteoporosis. Topical aspects at the present stage of study].

PMID- 9584655
TI  - [Rational choice of equipment for X-ray diagnostic unit].

PMID- 9584656
TI  - [The University of X-ray Laboratory Assistants. Lesson 3. Kerma in the air].

PMID- 9584657
TI  - [Some aspects of adverse reactions during radiopaque studies].

PMID- 9584658
TI  - Expanded programme on immunization (EPI). Progress towards poliomyelitis
      eradication in Africa, 1997.

PMID- 9584659
TI  - Malaria. Epidemiological surveillance, 1992-1996.

PMID- 9584660
TI  - The effects of insurance coverage and ethnicity on mammography utilization in a
      postmenopausal population.
AB  - Despite the effectiveness of mammography as a method to detect breast cancer in
      women ages 50 and older, many women do not obtain screening mammograms. This
      study used the self-reported mammography history and demographic information
      obtained during the screening of 2453 post-menopausal women ages 50 to 79 at the
      San Diego Women's Health Initiative (WHI) center. We used this data to examine
      individual and social factors that predict mammography use. The WHI center
      comprised two clinics, one of which focused on Hispanic recruitment and thus
      provided the opportunity to examine the roles of ethnicity, income, education,
      marital status, age, and access to medical services on mammography use. Bivariate
      analysis indicated that the following factors were all strongly associated with
      women having had a mammogram in the previous two years: having health insurance,
      a regular medical provider, an annual household income greater than $20,000, and
      a high-school diploma, as well as being 65 years or older or white (P < 0.001).
      Multiple logistic regression analysis demonstrated that, when adjusting for all
      of these factors, having a medical provider (P < 0.001) was significant. Having
      insurance (P = 0.04) was suggestive, but did not meet the multiple-comparisons
      significance cutoff of P = 0.006. After adjusting for the above factors, it was
      found that ethnicity was not significant. The results suggest that improved
      access to a regular provider could increase the use of screening mammography in
      underserved populations.

PMID- 9584661
TI  - Complementary medicine.
AB  - The widespread use of complementary and alternative medicine techniques, often
      explored by patients without discussion with their primary care physician, is
      seen as a request from patients for care as well as cure. In this article, we
      discuss the reasons for the growth of and interest in complementary and
      alternative medicine in an era of rapidly advancing medical technology. There is,
      for instance, evidence of the efficacy of supportive techniques such as group
      psychotherapy in improving adjustment and increasing survival time of cancer
      patients. We describe current and developing complementary medicine programs as
      well as opportunities for integration of some complementary techniques into
      standard medical care.

PMID- 9584662
TI  - Morbidity and mortality in the wilderness.
AB  - The medical literature is limited regarding current wilderness morbidity and
      mortality statistics. Available studies concentrate on selected wilderness
      activities. This study retrospectively examines wilderness injuries, illnesses,
      and mortality based on case incident report files from eight National Park
      Service parks within California over a three-year period. Data were extracted
      regarding type of illness or injury, body area affected, age, gender, month in
      which the event occurred, and activity in which the victim was involved at the
      time of the event. The overall occurrence of nonfatal events was 9.2 people per
      100,000 visits. More than 70% of all nonfatal events were related to
      musculoskeletal or soft-tissue injury. The most frequently involved body area was
      the lower limbs (38%). Seventy-eight mortalities occurred during the three years
      studied, resulting in an overall mortality rate of 0.26 deaths per 100,000
      visits. Men accounted for 78% of the deaths. Heart disease, drowning and falls
      were the most common causes of death. The information and statistics on morbidity
      and mortality in California wilderness areas that this study provides may be used
      to guide future wilderness use, education, and management. A standardized,
      computerized database would greatly facilitate future evaluations, decisions, and
      policies.

PMID- 9584663
TI  - Thromboangiitis obliterans. An update on Buerger's disease.
AB  - Buerger's disease (thromboangiitis obliterans) is a nonnecrotizing vasculitis
      affecting small and medium-sized arteries, typically in young male smokers. The
      diagnosis can often be made on the basis of a careful history and physical
      examination, together with ancillary laboratory studies. Occasionally
      arteriography is warranted to confirm the diagnosis. The pathological findings
      are distinctive and distinguish this disorder from other arterial occlusive
      diseases. Successful therapy is possible only with absolute abstinence from
      tobacco.

PMID- 9584664
TI  - Recent advances in stroke therapy.

PMID- 9584665
TI  - New approaches to therapy of amyotrophic lateral sclerosis.

PMID- 9584666
TI  - Status epilepticus.

PMID- 9584667
TI  - Drug treatment for Alzheimer's disease.

PMID- 9584668
TI  - The role of apolipoprotein E testing in the diagnosis of Alzheimer's disease.

PMID- 9584669
TI  - Genetic testing.

PMID- 9584670
TI  - Issues for women with epilepsy.

PMID- 9584671
TI  - New pharmacological and surgical therapies for Parkinson's disease.

PMID- 9584672
TI  - Recent advances in the treatment of neuropathies.

PMID- 9584673
TI  - Endovascular treatment of vasospasm.

PMID- 9584674
TI  - Combination therapy with an angiotensin converting enzyme inhibitor and an
      angiotensin-II receptor antagonist for refractory essential hypertension.

PMID- 9584675
TI  - Glibenclamide-induced cholestasis.

PMID- 9584676
TI  - Iliofemoral venous thrombosis treated by catheter-directed thrombolysis,
      angioplasty, and endoluminal stenting.

PMID- 9584677
TI  - Revascularization in coronary artery disease. A review of randomized trial data.
AB  - Since the advent of bypass surgery in the late 1960s and catheter-based
      intervention in the late 1970s, the treatment of coronary artery disease has been
      revolutionized by the concept of revascularization. Surveys have demonstrated
      that the practice patterns around the world and within the US are inconsistent
      for these important treatment options and are often driven by availability and
      economics rather than evidence-based data. In addition, the studies examining the
      use of medical therapy, balloon angioplasty, atherectomy, coronary stenting, and
      bypass surgery are consistently lagging behind the technological advances in this
      field. This article reviews the data that randomized trials and meta-analyses
      provide to compare these modalities. We attempt to provide a framework for
      reasoned clinical decision making to help guide patient care. While the
      breakpoints between the medicine bottle, cath lab, and operating room will
      continue to evolve, we offer a revascularization strategy for patient subgroups
      based on what clinical data supports.

PMID- 9584678
TI  - The answer is Buerger's disease, and the question is...

PMID- 9584679
TI  - What is the measure of a year?

PMID- 9584680
TI  - The brave new genetic world.

PMID- 9584681
TI  - Update on genetic dilemmas.

PMID- 9584682
TI  - Genetic testing. Harbinger of hope or landmine in the medical landscape?

PMID- 9584683
TI  - Testing the genetic waters.

PMID- 9584684
TI  - Ethics of genetic testing.

PMID- 9584685
TI  - Genetic counselors: what do they offer?

PMID- 9584686
TI  - An unusual chromosome rearrangement in a patient with features of the Wolf
      Hirschhorn syndrome.

PMID- 9584687
TI  - Physicians play role in genetic developments.

PMID- 9584688
TI  - Physician attitudes toward research study participation: a focus group.
AB  - The Wisconsin Research Network (WReN) and the UW Health Education And Research
      Trial (HEART) sponsored a focus group to explore the attitudes of primary care
      physicians toward research in their practices. Physicians, representing a variety
      of practice groups, emphasized that research is a low priority in their
      organizations. All had participated in some form of research, are philosophically
      committed to research as important to primary care, but are hesitant to commit
      themselves to participation in further research. They emphasized that academic
      researchers need to understand the constraints of primary care practice, propose
      research ideas that are practical and interesting to care providers, provide
      relevant feedback to participating practices, and do the majority of the research
      work themselves so impositions on the practice are minimal. The traditional
      barriers to practice-based research, such as the cost of physician and staff time
      and diversion from other tasks, continue to be of concern when physicians
      consider participation in research projects.

PMID- 9584689
TI  - Occupational exposure to laser surgery generated air contaminants.
AB  - The objective of the review is to show that scientific evidence is lacking on the
      safety of laser-generated air contaminants. Further research and data collection
      are necessary to characterize the potential dangers associated with exposures of
      health care professionals to laser generated air contaminants. The article is a
      review of existing scientific evidence in the area of exposure risks to health
      care professionals. A careful search of the scientific literature both in
      medicine and engineering was performed, as well as contact with experts from
      laser standards advisory sources. These sources include: International Laser
      Safety Conference, National Institute of Occupational Safety and Health, American
      National Standard Institute, Laser Safety Institute and Rockwell Laser
      Industries. The review includes articles in the literature documenting cases of
      over-exposures to contaminants while using a class IV laser, the same class laser
      used in surgery. Several studies of case reports of laser-generated air
      contaminants from cutting on human and animal tissues are included. Articles and
      guidelines on this subject of laser-generated contaminants from the above listed
      sources were used in writing this review. The review indicates that lasers used
      in surgery are potential occupational health risks.

PMID- 9584690
TI  - The next step: focusing on abusers in the health care system.

PMID- 9584691
TI  - Kinetic method for the assay of levodopa in pharmaceutical preparations.
AB  - A simple, rapid and accurate method for the analysis of levodopa using integral
      method, is described. The spectrophotometric measurements were recorded by
      measuring the increase in absorbance at 470 nm, when L-dopa was reacted with
      potassium iodate at room temperature. The kinetic parameters were calculated. The
      concentration range was valid from 60-700 ppm. The proposed kinetic method has
      been applied successfully to pharmaceutical preparations.

PMID- 9584692
TI  - Effect of shape factor on the release rate of drugs from lipid matrices.
AB  - It is usually quite difficult to obtain zero order release rate kinetic from
      matrix system. The release of drug from matrix is usually inversely proportional
      to the square root of time. It is shown in previous works that the release
      kinetics from the matrix system are strongly dependent on the matrix geometry. In
      this work, we aimed at producing zero order release kinetics by changing the
      shape of matrices. For this purpose, water soluble drug (Paracetamol) and
      slightly soluble drug (Ibuprofen) in the lipid matrices of hydrogenated cotton
      seed oil (HCSO) are used. Formulations are prepared in the shape of cylinder,
      slab, hemisphere and biconvex. In all formulations, the concentration of active
      material per unit volume is held constant. The rate of release of active material
      is determined by using the rotating basket dissolution test apparatus. The
      results are tested for Q-->square root of t and zero order kinetics. As a result,
      the hemispheric matrices are found to satisfy the requirements for constant
      release systems for both water soluble and slightly soluble drugs.

PMID- 9584693
TI  - Synthesis and cytotoxicity of the three-membered aromatic pyrimidine derivatives.
AB  - A series of the three-membered aromatic anthracene, acridine, carbazole
      substituted with pyrimidine moiety equipped with pharmacophoric chain of N'-(2'
      hydroxyethyl)ethylenediamine or dialkylamino-3-propylamine was obtained and
      tested for the cytotoxic properties in SRB test. The synthesis was performed from
      1,2,3,4-tetrahydro-6-methyl-2-oxo-4-thio-5-pyrimidinecarboxylic acid or its ethyl
      ester and three-membered aromatic amines (e.g. 9-aminoacridine). Some of the
      compounds showed significant cytotoxic activity.

PMID- 9584694
TI  - Synthesis and antitumor activities of some 4,5-dihydro-1H-1,2,4-triazol-5-ones.
AB  - Eight new 3-alkyl(aryl)-4-arylidenamino-4,5-dihydro-1H-1,2,4-triazol-5 - ones
      were synthesized and characterised by elemental analysis. 1H NMR, IR and UV
      spectra. Seven new and 34 recently reported derivatives of 4,5-dihydro-1H-1,2,4
      triazol-5-one ring were screened for their antitumor activities.

PMID- 9584695
TI  - Synthesis of N-benzyl-4-oxo-1,2,3,4-tetrahydrocinnolines.
AB  - The method of preparation of N1 and N2-substituted 4-hydroxycinnolines by
      alkylation with benzyl bromide of the corresponding 4-hydroxycinnolines is
      described. The obtained derivatives were reduced to the corresponding N-benzyl-4
      oxo-1,2,3,4-tetrahydrocinnolines. The effect of some synthesized derivatives on
      central nervous system was studied.

PMID- 9584696
TI  - Quality of drugs and adverse drug reactions.
AB  - Since 1986 National Pharmaceutical Inspection was involved in monitoring of drug
      safety. The number of reports received from Inspection was 842. They covered also
      reactions reported as concerns on the quality of drugs. Only 5.9% reported drugs
      did not conform with the quality tests. All others were assessed as suspected or
      confirmed adverse drug reactions.

PMID- 9584697
TI  - GABAA receptor agonist and antagonist modulate clonidine hypotension.
AB  - The effect of GABAA receptor agonist muscimol and antagonist picrotoxin on the
      hypotensive action of clonidine was investigated. Moreover, the GABA
      concentration in some brain areas in spontaneously hypertensive (SHR) and
      normotensive (WKY) rats was studied. It was demonstrated that co-dosage clonidine
      with the agonist or the antagonist modulates hypotensive effect of drug. Our data
      suggest that the clonidine interaction with these agents occurs at the level of
      GABAergic neurotransmission since clonidine and both compounds have been proved
      to influence the function of GABAergic neurons. It was also shown the lower GABA
      content in some brain areas of SHR than WKY rats. Based on the findings could be
      implicate that the stronger action of clonidine on blood pressure in SHR is also
      connected with alterations of other neurotransmitter systems involving in its
      hypotensive effect.

PMID- 9584698
TI  - Effect of ethanol dose on its chronopharmacokinetics in the rats.
AB  - Circadian changes in the elimination of ethanol after its administration in the
      rats in two doses: low (1.5 g/kg) and high (4.5 g/kg) were investigated.
      Circadian rhythm in ethanol pharmacokinetics (AUC, CLpo, t1/2) was observed after
      the low dose but not after the high one. The maximum rate of elimination was in
      the dark (active) phase at 1 am. The maximum value of clearance was related to
      the minimum value of AUC. Although the maximum and the minimum values of Vmax and
      KM differed essentially the diurnal variation were not observed.

PMID- 9584699
TI  - Preventive quadrant restorative dentistry effective yet overlooked.

PMID- 9584700
TI  - Temporary crowns--want better results?

PMID- 9584701
TI  - Prosthodontics and the aging patient.
AB  - As an increasing percentage of our population is growing older and suffering from
      chronic medical conditions, the ability of the dentist to treat these patients is
      becoming more important. The dentist must be aware of the these patients'
      physiology and changing anatomy as well as their psychosocial needs. Changes in
      oral and dental tissues related to aging, as well as limitations in this
      population's perceived dental care needs, are presented. Modifications in the
      practice of fixed, removable partial, and complete denture prosthodontics as
      related to the management of the geriatric patient by the general practitioner
      are discussed.

PMID- 9584702
TI  - Root caries in the elderly: an update for the next century.
AB  - Root caries is an emerging challenge to the dental professions because of the
      growing number of increasingly aging adults who have retained many or all of
      their teeth. Risk factors for developing root caries point to both intraoral and
      environmental factors, making the management of root caries complex and
      multidisciplinary. Prevention is the most desirable approach for management, but
      patients who have developed caries of the roots can be treated with
      remineralization strategies or a variety of restorative approaches. Dental
      professionals need to keep abreast of new approaches emerging for the management
      of root caries.

PMID- 9584703
TI  - Preventive strategies for the older dental patient.
AB  - The purpose of this article is to review preventive strategies with regards to
      caries, periodontal disease, xerostomia, and oral cancer which may be helpful in
      treating the older patient. Dramatic demographic changes projected for the older
      population will have a direct impact on the type and quantity of dental services
      delivered in the future. It will be advantageous for tomorrow's oral health
      professional to recognize these changes and to adapt preventive and treatment
      regimens accordingly.

PMID- 9584705
TI  - Soft thermoplastics in bruxism appliances.

PMID- 9584704
TI  - Neurological disorders in dentistry: managing patients with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent type of dementing illness
      affecting over four million Americans. It typically occurs after age 60, and
      prevalence increases with advanced age. As the adult population increases, a
      greater number of patients with a diagnosis of AD will require dental care. This
      article reviews the oral and systemic clinical findings seen in AD patients and
      current medical treatment. Some general and specific suggestions for dental
      management are presented, including guidelines for restraint and sedation use.
      Finally, some helpful, adaptive oral devices are recommended for use by
      caregivers of patients unable to provide for their own daily oral hygiene. Dental
      providers can and should be willing to make oral care available to patients with
      a diagnosis of AD. Despite the difficulties involved, the need will continue to
      be great, and the gratification in caring for these patients makes it worth the
      effort.

PMID- 9584706
TI  - Bone, dental implants and biomechanics. A close look at the restorative needs of
      patients with dental implants: Part 3.

PMID- 9584707
TI  - Customized sub-structure abutments for implants.

PMID- 9584708
TI  - Color characterization of denture base material.
AB  - The time taken to create a more natural prosthesis by twisting a tooth, carving
      wax and applying a few basic colors can make a world of difference for patients
      wearing dental prosthesis. The technician can achieve a natural resemblance of
      tissue coloration in the oral cavity when these procedures are applied.

PMID- 9584709
TI  - Mastering the dental surveyor: an instrument for the whole laboratory.

PMID- 9584710
TI  - Fixed partial denture segmenting attachments.

PMID- 9584711
TI  - Soft tissue models: the key to esthetic success.

PMID- 9584712
TI  - Provisionals: not just temporaries.
AB  - When a provisional is to be worn for an extended period of time, the laboratory
      processed provisional may be indicated because of its strength, wear-resistance
      and resistance to discoloration. A large selection of shades are available,
      resulting in better esthetics. The incisal blend gives the provisional a
      translucent effect. Office visits for repairs and maintenance will be minimized.
      If the patient has confidence after the provisional visit, he or she will have
      equal confidence in the final restoration. The only difference between the two
      should be the materials used.

PMID- 9584713
TI  - Basic biomechanical considerations for implant case planning.

PMID- 9584714
TI  - Computerizing the small dental laboratory. What's available and how to buy it.

PMID- 9584715
TI  - Implant screw retained dentures.

PMID- 9584716
TI  - The arch expansion paradigm: Edward Angle's theories revisited.

PMID- 9584717
TI  - Case report: gingival abrasion due to a "chin ring".

PMID- 9584718
TI  - Parameters of care for the American College of Prosthodontists. POC version 1,
      March 1996.

PMID- 9584719
TI  - Dispute resolution for the dental profession.

PMID- 9584720
TI  - Retiring some myths about aging and oral health.
AB  - Research on the oral health status of elderly populations has been limited in
      frequency and scope. There is a lack of good descriptive and longitudinal data on
      salivary gland function, oral mucosal status, and oral sensory performance in
      health and disease across the adult life span. Thus, confusion for practitioners
      and patients alike arises from unsubstantiated stereotypes about aging and oral
      health. There are some commonalities in the origins of the myths discussed in
      this article. First, many aging generalizations were based on studies that did
      not account for the health and medication status of the subjects. Second, most
      aging studies are cross-sectional designs which can result in misleading
      conclusions due to the age cohort effect. Third, many studies on the histology of
      aging oral tissues were laboratory animal studies, with results that cannot be
      generalized to human populations. Fourth, findings on oral health changes are
      often confounded or influenced by differences in functional status (e.g., the
      ability to care for oneself), nutritional health, health beliefs and expectations
      within the study subjects. Fifth, other changes due to aging may have an indirect
      effect on oral health, for example, an age-related decline in immune function.
      Sixth, the "older-old" group of elderly commonly labor under misconceptions of
      normal aging changes. Historically they have not sought dental care as often as
      the younger elders. This health care seeking behavior is expected to change
      dramatically when the baby boom generation joins the elderly ranks. The goals of
      oral health care for the elderly are consistent with those of other health care
      providers involved in geriatric care, namely maximizing functional performance,
      fostering independence, and enhancing their quality of life. Dental professionals
      would be well advised to apply a healthy dose of skepticism to any
      generalizations about debilitating changes in oral health due to aging alone.
      Most changes in oral health experienced by the elderly are not the result of age
      itself, but are the consequences of systemic disease, pharmacotherapy, functional
      disabilities, and cognitive impairment. When unexplained deleterious changes are
      seen in the oral health of elderly patients, the knowledgeable and reflective
      practitioner will account for local, systemic, and environmental factors in
      formulating a plan of care. In the opening paragraph, questions were posed about
      the mucosal integrity of a "little old lady." The most beneficial approach for
      her and all our older patients is to plan treatment utilizing current knowledge
      about aging and avoiding the traps created by myths and stereotypes. It is time
      to retire these myths before the baby boomers join the ranks of the retired.

PMID- 9584721
TI  - "Pediatric dentistry today".

PMID- 9584722
TI  - Porcelain inlays and onlays: why, when, and how.

PMID- 9584723
TI  - Unlocking your professional and personal success through practice valuation.

PMID- 9584724
TI  - Medical risk report: the dental patient with cancer.

PMID- 9584725
TI  - Medical risk report: the dental patient with developmental disabilities.

PMID- 9584727
TI  - Preparing for the "silver age of dentistry".
AB  - Providing oral health care to older adults will be a challenging and rewarding
      part of dental practice in the years ahead. It will include understanding normal
      aging, appreciation of the pathophysiology of chronic diseases experienced by
      many elderly, and application of key principles of pharmacology in care of
      patients receiving medications for treatment of these diseases. It will involve
      an understanding of the interaction of systemic conditions with oral health
      status, adequate diagnosis of oral disease, and appropriate rational treatment
      planning with a strong emphasis on preventive dentistry. It will include care
      provided in nursing homes or during housecalls for the homebound. Dentist
      geriatricians will be working with teams of healthcare professionals that include
      physicians, dentists, podiatrists, ophthalmologists, nurses, social workers,
      nutritionists, pharmacists, and occupational and physical therapists. Above all,
      the team will provide skilled compassionate care, which is always good business!

PMID- 9584726
TI  - Fluoride concentration in milk, tea and bottled water in Houston.

PMID- 9584728
TI  - Digital image analysis in the office.

PMID- 9584729
TI  - "Health care providers and the Texas Deceptive Trade Practices Act".

PMID- 9584730
TI  - Dental implant loading.

PMID- 9584731
TI  - New study finds Florida dental AIDS patients victims of serial homicide.

PMID- 9584732
TI  - Building lasting relationships with your "mystery patients".

PMID- 9584733
TI  - Medical risk report: the dental patient with cardiovascular disease.

PMID- 9584734
TI  - Medical risk report: the dental patient with diabetes.

PMID- 9584735
TI  - Medical risk report: the dental patient with renal failure.

PMID- 9584736
TI  - Medical risk report: the dental patient with acquired bleeding disorders.

PMID- 9584738
TI  - Water fluoride level in Houston Independent School District 10-years after
      fluoridation.

PMID- 9584737
TI  - Medical risk report: improving patient management and record keeping through a
      problem-oriented approach.
AB  - The problem-oriented record satisfies the needs of the contemporary practitioner
      by addressing the transition from diagnosis to treatment. The technique organizes
      collected data, identifies all patient problems (medical and dental), defines
      solutions and/or management of those problems, and documents treatment rendered.
      Predictably, the problem-oriented record will avoid problems associated with
      malpractice litigation, conform to regulations of third-party payers, and
      facilitate practice analyses and quality assessment, i.e., through computer
      assisted tracking of patient care based on problems and not just treatment
      rendered. As many practices today focus on a "patient-centered" approach to
      practice, the problem-oriented record clearly supports such a philosophy in its
      completeness of managing patient care information. The dentist, in consultation
      with other health care providers, can and should feel confident treating patients
      from the growing population of patients with medical risk. By integrating the
      problem-oriented approach into patient management and record keeping, dentists
      can more easily develop a plan for the complexities that accompany patients.
      Whether these complexities are of a medical, dental, or combined nature, the
      problem-oriented record helps the practitioner organize information, plan for
      treatment, and document patient care in a complete and concise manner.

PMID- 9584739
TI  - Denture stomatitis secondary to a homemade denture adhesive.

PMID- 9584740
TI  - Management of dry mouth in elderly patients.
AB  - Xerostomia is not a natural consequence of the aging process. Although dry mouth
      is not often found to be a chief complaint of elderly patients, it is a common
      problem that usually receives inadequate attention. Xerostomia is the feeling of
      dry mouth due to insufficient secretion of saliva. It is most common among the
      elderly as a result of adverse effects of drug therapy, head and neck radiation,
      or autoimmune diseases. Chronic xerostomia has a debilitating effect on the
      integrity of the hard and soft tissues of the mouth. It often causes difficulty
      in speaking, tasting, eating, swallowing and denture retention. The goals of
      treatment are to stimulate salivary flow, or to restore oral moistness and
      prevent or alleviate the uncomfortable, harmful sequelae of xerostomia. Dentists
      can significantly enhance the quality of life for xerostomia sufferers by
      effectively managing the xerostomia sequelae in a compassionate, understanding
      manner.

PMID- 9584741
TI  - The new supplemental fluoride dosage schedule.

PMID- 9584742
TI  - The surgical operating microscope in endodontics.

PMID- 9584743
TI  - Squamous cell carcinoma of the floor of the mouth with invasion of the mandible.

PMID- 9584744
TI  - Practice evaluation: earning power or blue sky?

PMID- 9584745
TI  - Eastern Health Board Regional Orthodontic Service: an initial audit.
AB  - This initial audit of 600 recently assessed Eastern Health Board orthodontic
      patients suggests that a large number of them (47 per cent) requires referral for
      routine restorative and preventive dental care. Closer links are needed with
      general dental practitioners and community dental surgeons to resolve these
      needs. The trend for a high referral of females and Class 11 Division 1
      malocclusion type correlated well with studies in other countries.

PMID- 9584746
TI  - Orthodontic treatment using functional appliances.

PMID- 9584747
TI  - A review of dental amalgam and substitutes.

PMID- 9584748
TI  - Ectodermal dysplasia: a case report.
AB  - Ectodermal dysplasia is a rare group of inherited disorders, transmitted as an X
      linked recessive. Patients with ectodermal dysplasia usually exhibit a fine
      smooth dry skin, with partial or complete absence of sweat glands. The main
      dental manifestation is hypodontia, which is of variable severity. Peg shaped
      teeth and reduced vertical dimension are also frequently present. In this report
      a case of ectodermal dysplasia which presented at the Cork University Dental
      School and Hospital is discussed.

PMID- 9584749
TI  - A localised oral health study based on the School Dental Inspection system, and
      its implications for the proposed national oral health database.
AB  - From 1989 to 1994, the author carried out a dental health study on all children
      examined in two age groups during the routine annual School Dental Inspection.
      Dual criteria were applied; the first a clinical diagnosis to prioritise each
      child for follow-up dental treatment, and the second using standardised criteria
      for use in an epidemiological study. The two sets of information were kept
      separately. Analysis showed that the methodology was capable of eliciting
      differences in dental disease levels between adjacent localised geographical
      areas, and trends in disease levels over time. Fluctuations in the uptake of
      dental treatment, but not in actual caries levels. Although epidemiological
      information collected in this way may not be as reproducible as that collected in
      highly organised epidemiological point prevalence studies, it has several
      advantages in that large numbers of subjects may be examined with relatively
      little extra resources. The School Dental Inspection system may be a template on
      which localised data may be collected to form part of the proposed national oral
      health database. A follow-up study is proposed to assess how the twin track
      approach of an improved system of localised information collection based on the
      School Dental Inspection system coupled with standardised epidemiological studies
      might provide a framework for a system which would provide useful data at
      different levels of what is essentially a multi level dental service.

PMID- 9584750
TI  - Prevalence of dentine hypersensitivity in a general dental population.
AB  - The aim of this study was to determine, by questionnaire, the reported levels of
      dentine hypersensitivity in adult patients attending general dental practice. A
      total of 250 subjects (88 males, aged 40 +/- 14.3 years; 162 females aged 37 +/-
      11.6 years), were recruited to the study in 5 dental practices. The prevalence of
      reported sensitivity was 57.2%, most frequently occurring in the 30-39 year age
      group. In the vast majority of cases (89.3%) cold was the major stimulus for
      pain, other commonly reported causes being toothbrushing (38.6%), hot (37.9%) and
      sweet (25%) stimuli. Desensitising toothpastes were used by 67.9% of those
      reporting sensitivity, the majority of these (72.6%) reporting a beneficial
      effect. Professional treatment had been sought by 32% of subjects, almost all
      (91%) reporting an improvement post-treatment. There was no significant
      correlation in the level of reported sensitivity and previous periodontal
      treatment. The majority of subjects with sensitivity also smoked (67.6%),
      although this relationship did not reach statistical significance (p = 0.07).
      Visual analogue scales indicated that perceived pain levels with dentine
      sensitivity were relatively low. It was concluded that the prevalence of dentine
      sensitivity found in this study was much higher than previously reported,
      suggesting an increase in the levels of sensitivity within the general
      population.

PMID- 9584751
TI  - Oral surgery demands of a regional orthodontic unit.
AB  - The orthodontic records of patients attending a Regional Orthodontic Unit, and
      who were referred for specialised oral surgery procedures were examined. From
      January, 1995 to December, 1995, 22 patients were referred for treatment. The
      majority of these patients required exposure or extraction of unerupted maxillary
      canine teeth. Over 77% of patients requested this treatment through the Public
      Health Service resulting in long waiting lists developing for receipt of
      treatment.

PMID- 9584752
TI  - Class III malocclusions: the choice between orthodontics or surgery.
AB  - In summary, orthodontic treatment tends to be successful if there is:- Low
      Maxillomandibular planes angle Little Compensation Small reverse overjet
      Symmetric growth pattern Failure occurs due to:- Unfavourable growth pattern High
      degree of compensation Large negative overjet The treatment of the Class III
      malocclusions is considered. The extent to which Class III cases can be treated
      with Orthopaedic appliances is outlined and discussed. The positive and negative
      factors influencing the decision for orthodontic or surgical treatment are
      considered and finally stability is examined.

PMID- 9584753
TI  - Experiences with sedation and restraint during dental treatment in Romania.
AB  - In August, 1995 dental treatment was provided in an orphanage in Romania. This
      treatment took place over three weeks using three different dentists. Two dental
      nurses served for full the duration. For the last two weeks the team was joined
      by a dental health educator. All have given accounts of their time in Romania.
      The patients had various degrees of handicap but generally co-operation for
      treatment was poor. Most patients needed pre-operative sedation of oral valium. A
      papoose board was used for restraint. All the contributors agree that this was
      extremely helpful in controlling the patients. Dental treatment was mostly
      restricted to extractions. A parallel preventive programme was run by the dental
      health educator. The team encountered bureaucratic problems which were overcome.
      All 220 children in the orphanage were screened and treated. Local children and
      adults were also given dental treatment when time allowed. The team wish to
      express gratitude to all who helped and supported them. They plan a future
      mission in 1997. In 1994, a dental team had previously travelled to Romania and
      carried out treatment of handicapped children using sedation & restraint. The
      principal difference between 1994 and 1995 was the introduction of the papoose
      board as the method of restraint. The papoose board is a temporary restraint
      device for use during medical or dental procedures. It is a set of canvas flaps
      with velcro fasteners on a board. A head strap and wrist straps are important
      accessories. Pre-operative sedation was given to the children 2-3 hours in
      advance of dental treatment. This usually was 10-20 mg oral valium. The child was
      then led into the dental surgery by hand and placed on the papoose board, which
      was already situated on the reclined dental chair. Before the child realised what
      was happening the wrist straps and leg straps were in place. Within seconds the
      other straps were closed and the child was totally restrained and ready for
      dental treatment. Dental treatment was then carried out using local anaesthesia.
      Care has to be taken that the restraint does not impair the patient's breathing,
      circulation, cause over-heating or positional injuries. A dental health education
      programme was run in parallel with the treatment service. The individual accounts
      of experiences follow. Firstly, the joint account of Dental Nurses Catherine
      Treacey and Karen Vaughan from the Dublin Dental Hospital, who were working for
      the full three weeks. Then follow the accounts of the dentists. On week 1 by Anne
      O'Neill, who works with the Eastern Health Board in the Dun Laoghaire area, week
      2 by Robert Gorby, a dentist in private practice in Carlow, and week 3 by Brendan
      Fanning who works part-time for the Eastern Health Board, in Wicklow and part
      time in practice in Ashford, Co. Wicklow. The final account is of the dental
      health education programme by Miriam Henshaw, Health Educator who works for the
      Eastern Health Board in the Wicklow area.

PMID- 9584754
TI  - Root resorption and the impacted canine.
AB  - This article considers the incidence and outcome of incisor root resorption in
      cases where the upper permanent canine is impacted. A review of the associated
      factors indicates that it is not possible to predict when resorption will occur
      and so all impacted canines, whether buccal or palatal, should be regarded as
      potentially damaging. The management is discussed and illustrated by showing some
      examples.

PMID- 9584755
TI  - Class III malocclusions: the choice between orthodontics or surgery.
AB  - In summary, orthodontic treatment tends to be successful if there is:- Low
      Maxillomandibular planes angle Little compensation Small reverse overjet
      Symmetric growth pattern Failure occurs due to:- Unfavourable growth pattern High
      degree of compensation Large negative overjet The treatment of the Class III
      malocclusions is considered. The extent to which Class III cases can be treated
      with Orthopaedic appliances is outlined and discussed. The positive and negative
      factors influencing the decision for orthodontic or surgical treatment are
      considered and finally, stability is examined.

PMID- 9584756
TI  - Costs in providing facilities for treatment of handicapped patients under general
      anaesthesia.
AB  - The cost of providing dental treatment for severely mentally/physically
      handicapped patients under general anaesthesia in a specially designed unit are
      investigated in this study. The costs involved in the provision of such treatment
      were found to be high at 613 IR Pounds per patient. It is recommended that the
      full potential of primary care services for handicapped patients be developed in
      order to reduce the use of these necessary, but expensive secondary care
      facilities. It is also recommended that such facilities should be shared with
      other services in order to reduce overall costs.

PMID- 9584757
TI  - A survey of continuing dental education in the South and Mid-West Region of the
      Postgraduate Medical and Dental Board.
AB  - This paper presents the data from the analysis of Feedback Questionnaires
      obtained from dentists who attended Continuing Education Courses run by the
      Postgraduate Medical and Dental Board, South & Mid-West Region form 1992 to 1994.
      The implications of the findings are discussed.

PMID- 9584759
TI  - Dental fellowship training in Malaysia--a personal experience.

PMID- 9584758
TI  - Dental caries treatment pattern in 14-15-year-old school pupils attending high
      caries schools in north & west Belfast and their ability to recognise untreated
      disease.
AB  - The study examined the dental caries treatment profile of 186 14-15-year-old
      children in schools known previously to have a high overall caries experience,
      the schools being located in a high caries area of Northern Ireland. The children
      had a high mean number of decayed and untreated teeth. The majority of children
      who had untreated decay were unaware of this status and had a mean D value of
      3.85. There was a significantly higher number of untreated carious teeth for
      children who had not attended a dentist within the past year when compared with
      those who had attended (mean values 4.08 and 2.54 respectively). While there were
      high levels of unmet needs overall it is concluded that children who had not
      attended the dentist for the past year had very high levels of untreated decay.

PMID- 9584760
TI  - Talon cusps: a review.

PMID- 9584761
TI  - Fabricating ceramometal restorations.

PMID- 9584762
TI  - Lyme disease awareness for the New Jersey dentist. A survey of orofacial and
      headache complaints associated with Lyme disease.
AB  - The incidence of Lyme disease is increasing in New Jersey. In 1996, 2,190 cases
      were reported, representing an increase of 487 cases from the 1,703 reported in
      1995 [Table 1]. Symptoms associated with Lyme disease include headache and facial
      pain that often mimics dental pathology and temporomandibular disorders. Patients
      with complaints of vague, non-specific dental, facial or head pain, who present
      with a multisystemic, multi-treatment history, are suspect. This article
      discusses Lyme disease in New Jersey and the clinical presentation of Lyme
      disease that the dental practitioner may encounter. A summary of data is provided
      which was collected from 120 patients diagnosed with laboratory confirmed Lyme
      disease. The most common orofacial, head and dental complaints seen in the Lyme
      disease patient are reviewed. This information will hopefully aid in establishing
      a diagnosis and appropriate referral where indicated.

PMID- 9584763
TI  - Premolar distalization to eliminate the free-end removable partial denture.
AB  - This article is intended to give an overview of an alternative treatment plan for
      mandibular posterior replacements and descriptions of techniques. Practitioners
      who possess a basic knowledge of fixed prosthodontics and corrective orthodontic
      capabilities could successfully treat such a case.

PMID- 9584764
TI  - Fen-phen's message to dentists.

PMID- 9584765
TI  - 1996 demographic characteristics and distribution of dental hygienists in
      Kentucky.

PMID- 9584766
TI  - Ethical dilemma. What would you do?

PMID- 9584767
TI  - Implant update.

PMID- 9584768
TI  - Case presentation. Hand, foot, and mouth disease.

PMID- 9584769
TI  - Smoking as a risk factor for gingival problems, periodontal problems and caries.
AB  - Lack of uniformity in the classification of oral diseases, and variability of
      study designs, measurements, methods, and statistical formats, hamper the
      interpretation, comparison and review of the evidence linking smoking and oral
      diseases. However, there have been a significant number of controlled studies,
      allowing definitive conclusions to be drawn. This review of 22 controlled
      scientific studies from 1983-1992, considers the role of smoking as an
      aetiological agent in: gingival problems (impaired gingival bleeding, ANUG),
      periodontal problems (periodontitis, bone loss, tooth loss), and caries.

PMID- 9584770
TI  - Iatrogenic effects of orthodontic treatment. Part II: Demineralization.

PMID- 9584771
TI  - Dental caries and periodontal disease in Down's syndrome patients.

PMID- 9584772
TI  - Test your diagnostic skills. Congenital epulis.

PMID- 9584773
TI  - Comprehensive endodontics for special needs patients: a case report.

PMID- 9584774
TI  - The bonded amalgam restoration.

PMID- 9584775
TI  - Current recommendations for appropriate use of fluoride supplements for the
      prevention of dental caries.

PMID- 9584776
TI  - Test your diagnostic skills. Pyogenic granuloma.

PMID- 9584777
TI  - Emphasis on prevention in your office for today's dental needs.

PMID- 9584778
TI  - Extensive maxillary odontogenic keratocyst: review of the literature and report
      of a case.
AB  - Odontogenic keratocysts arising in the maxilla are relatively uncommon, small
      unilocular lesions that rarely involve the maxillary sinus. This paper reviews
      the clinical, radiologic and histologic features of an extensive maxillary
      odontogenic keratocyst involving the maxillary sinus, and the complications
      associated with its management. The authors emphasize the importance of regular
      patient follow-up examinations and imaging studies in order to detect and treat
      recurrent lesions when they are small and well-localized.

PMID- 9584779
TI  - Latex allergy.

PMID- 9584780
TI  - Test your diagnostic skills. The van der Woude syndrome.

PMID- 9584781
TI  - Technical considerations related to the use of thermoplasticized gutta percha.

PMID- 9584782
TI  - Periodontal treatment for the medically and physically compromised patient: a
      case report.

PMID- 9584783
TI  - Mandibular functional displacements: dual bites: a case report.

PMID- 9584784
TI  - Iatrogenic effects of orthodontic treatment. Part I: Root resorption.

PMID- 9584785
TI  - Test your diagnostic skills. Odontogenic keratocyst.

PMID- 9584786
TI  - Stafne bone defect.

PMID- 9584787
TI  - Iatrogenic effects of orthodontic treatment. Part III: Debonding.

PMID- 9584788
TI  - Cowden's syndrome: a case report.

PMID- 9584789
TI  - Dental management of the patient on hemostatic pharmacotherapy.

PMID- 9584790
TI  - Test your diagnostic skills. Ameloblastoma.

PMID- 9584791
TI  - Musculoskeletal dysfunction associated with the practice of dentistry--proposed
      mechanisms and management: literature review.

PMID- 9584792
TI  - Asthma, diabetes and hypertension: diseases and medical histories.
AB  - Virtually all dental offices are asked to treat patients with underlying medical
      concerns. Because of their high prevalence in our society, we are obligated to
      have some familiarity with asthma, diabetes, and hypertension. Dental treatment
      can affect or be affected by these diseases. Our mandate as health care
      professionals to "do no harm" dictates that we must be prepared to properly
      assess all patients in determining how, and if, they may be treated safely. Good
      medical histories and physical examinations are the only ways to do this. When
      faced with a medically compromised patient, the following recommendations apply:
      Have a working knowledge of the disease. Prepare your facility for a crisis.
      Consider your reasonable prevention protocols and use them as appropriate. Avoid
      known triggers. Plan to lower stress.

PMID- 9584793
TI  - An assessment of oral health needs of the community served by West Central
      Community Health Centres.

PMID- 9584794
TI  - Test your diagnostic skills. Lymphoma.

PMID- 9584795
TI  - Odontogenic infections and clindamycin.

PMID- 9584796
TI  - The restoration of endodontically treated teeth.

PMID- 9584797
TI  - Massive cemento-ossifying fibroma: case report.

PMID- 9584799
TI  - Test your diagnostic skills. Lichen planus.

PMID- 9584798
TI  - Dental management of the gravid patient and nursing mother.

PMID- 9584800
TI  - Radiology forum. Simple bone cyst.

PMID- 9584801
TI  - Evaluation of the protective value of hospital gowns against blood strike-through
      and methicillin-resistant Staphylococcus aureus penetration.
AB  - BACKGROUND: Hospital gowns protect patients and health care workers from exposure
      to blood and other infectious materials. Previous studies have shown that certain
      gowns do allow blood strike-through. Because of worldwide increases in the
      incidence of Staphylococcus aureus infections, especially with methicillin
      resistant strains, there is now increased concern regarding bacterial
      transmission through gowns. METHODS: This study evaluated six gown types used in
      hospitals (one disposable cover or isolation gown, three disposable operating
      room gowns, and new and washed reusable operating room gowns). Gowns were
      evaluated for dry spore and S. aureus filtration efficiencies and were subjected
      to 20 time-pressure combinations with methicillin-resistant S. aureus-spiked
      blood (10(4)/ml) to evaluate blood strike-through and passage of methicillin
      resistant S. aureus. RESULTS: Blood strike-through was lowest with disposable
      operating room gowns 1 and 2 (polypropylene). Disposable operating room gown 3
      (polyester-wood pulp) showed the greatest strike-through and overall passage of
      methicillin-resistant S. aureus. Operating room gowns 1 and 2 showed minimal
      bacterial passage, whereas the disposable cover (polypropylene) only allowed
      passage at pressures greater than 1 psi. Bacterial filtration efficiency testing
      showed operating room gowns 1 and 2 to be the most protective; operating room
      gown 3 and both reusable (cotton) gowns were the least protective. Dry spore
      passage was greatest for reusable gowns. CONCLUSION: Different hospital gowns
      offer varying degrees of protection against fluid strike-through or bacterial
      passage. Gowns therefore should be chosen according to the task performed and
      conditions encountered.

PMID- 9584802
TI  - Inactivation of human immunodeficiency virus type 1, hepatitis A virus,
      respiratory syncytial virus, vaccinia virus, herpes simplex virus type 1, and
      poliovirus type 2 by hydrogen peroxide gas plasma sterilization.
AB  - BACKGROUND: Studies were conducted to determine the capability of a hydrogen
      peroxide gas plasma sterilization process to inactivate several types of viruses.
      Six test agents were used: HIV type 1, human hepatitis A virus, respiratory
      syncytial virus, vaccinia, herpes simplex virus type 1, and poliovirus type 2.
      METHODS: The test viruses were suspended in cell culture medium and dried on the
      bottom of sterile glass petri dishes. The inoculated dishes were processed in the
      hydrogen peroxide gas plasma system for half the normal sterilization cycle time.
      Four inoculated carriers for each virus were used in two separate half cycles.
      Infectivity of the test viruses and cytotoxicity to the indicator cell lines were
      assayed. RESULTS: The hydrogen peroxide gas plasma sterilization process produced
      inactivation of the six viral test agents under these experimental conditions.
      The reduction in viral titers ranged from 2.5 log10 to 5.5 log10, a 99.68% to
      99.999% decrease. CONCLUSIONS: These results clearly demonstrate the virucidal
      effectiveness of the hydrogen peroxide gas plasma sterilization process against
      both lipid and nonlipid viruses.

PMID- 9584803
TI  - Methicillin-resistant Staphylococcus aureus outbreak: a consensus panel's
      definition and management guidelines.
AB  - OBJECTIVE: To provide medical personnel with a definition of an outbreak of
      methicillin-resistant Staphylococcus aureus (MRSA) and guidelines for managing
      potential outbreaks. PARTICIPANTS: Eighteen panel members were chosen from
      different specialties, types of institutions, and geographic regions.
      Representatives from the American Society of Consultant Pharmacists, the American
      Society of Health-Systems Pharmacists, the Society for Healthcare Epidemiology of
      America, and the National Association of Directors of Nursing Administration
      participated. CONSENSUS PROCESS: In preparation for the conference, panel members
      reviewed the literature and wrote abstracts outlining their personal opinions on
      the core issues, which were circulated to all participants. During a weekend
      conference, the panel summarized the reviewed literature, defined an MRSA
      outbreak, and developed management guidelines. EVIDENCE: Published literature,
      clinical experience, and expert opinion concerning the emergence and subsequent
      management of MRSA cases in health care institutions. RESULTS: An outbreak of
      MRSA was defined as either an increase in the rate of MRSA cases or a clustering
      of new cases due to the transmission of a single microbial strain in the health
      care institution. An increased rate of cases can be defined statistically or
      experientially and includes both infected and colonized patients. A potential
      outbreak should trigger stepwise, multidisciplinary actions consisting of basic
      epidemiologic procedures (phase I) to form an initial epidemiologic hypothesis of
      an outbreak (phase II) followed by a standard epidemiologic workup (phase III)
      and microbiologic studies (phase IV) to confirm the hypothesis. Mupirocin calcium
      treatments should be considered to decolonize health care workers during the
      fourth phase, even before typing is completed. CONCLUSIONS: Until studies can be
      conducted to delineate the effectiveness of different recommendations, the
      proposed guidelines may provide a useful starting point that can be adapted to
      meet an individual institution's specific needs.

PMID- 9584804
TI  - Sanitary care and maintenance of ice-storage chests and ice-making machines in
      health care facilities.
AB  - In response to a reported hospital outbreak traced to the use of contaminated ice
      in 1968, the Centers for Disease Control and Prevention (CDC) developed an
      advisory regarding the sanitary care and maintenance of ice-storage chests and
      ice-making machines. CDC has revised this unpublished advisory several times
      during the years to respond to requests for guidance from infection control
      professionals. Because CDC continues to receive inquiries about this topic from
      infection control professionals, this advisory is being published.

PMID- 9584805
TI  - APIC strategic planning member survey, 1997. Association for Professionals in
      Infection Control and Epidemiology, Inc.

PMID- 9584806
TI  - Measuring and improving the performance of health care providers: accreditation
      in the 21st century.
AB  - Outcomes data will become part of the Joint Commission on Accreditation of
      Healthcare Organizations' accreditation process. Accredited organizations will
      select a measurement system that they will use to submit data to the Commission.
      Data trends will be reviewed to determine response by the accreditor. The Joint
      Commission will work with organizations to assist with improvement opportunities.
      Accreditation decisions will continue to be based on standards. The Joint
      Commission's system, the IMSystem, is one of several systems available for use in
      accreditation activities.

PMID- 9584807
TI  - Hydrogen peroxide gas plasma sterilization is effective against Cryptosporidium
      parvum oocysts.
AB  - The aim of this work was to evaluate in an immunosuppressed rat cryptosporidiosis
      model a new method that combines vacuum and low-temperature hydrogen peroxide gas
      plasma for sterilization of endoscopic material contaminated by Cryptosporidium
      parvum. Rats were challenged with oocysts either air-dried or air-dried and
      treated with vacuum alone or associated with gas plasma. No rat was found
      infected after gas plasma exposure of oocysts, whereas vacuum or air-drying alone
      resulted only in a decreased infectivity.

PMID- 9584809
TI  - Levels of microbial contamination on surgical instruments.
AB  - OBJECTIVE: To ascertain the microbial load and type of organisms on used surgical
      instruments following standard cleaning, which consisted of the use of a washer
      sterilizer followed by sonic cleaning. DESIGN: In this prospective experimental
      study, used surgical instruments were immersed in Peptamin Tween broth, the broth
      agitated, and then filtered through a 0.45 microm filter. Quantitative cultures
      were performed, and all microbes were identified by using standard techniques.
      SETTING: This study was conducted at a 660-bed university hospital. RESULTS: The
      microbial load remaining on used surgical instruments after cleaning was as
      follows: 36 (72%) instruments 0 to 10 colony-forming units (CFU), 7 (14%)
      instruments 11 to 100 CFU, and 7 (14%) instruments > 100 CFU. Organisms
      contaminating the instruments included coagulase-negative staphylococcus (56%)
      followed by Bacillus (22%) and diphtheroids (14%). No other microbes were
      isolated from more than 4% of the instruments. CONCLUSION: Most used nonlumen
      surgical instruments contain less than 100 CFU of relatively nonpathogenic
      microorganisms after cleaning. This suggests that new low-temperature
      sterilization technologies are likely to be highly effective in preventing cross
      transmission of infection via nonlumen medical instruments.

PMID- 9584808
TI  - Tuberculosis control through respirator wear: performance of National Institute
      for Occupational Safety and Health-regulated respirators.
AB  - BACKGROUND: In 1995 the National Institute for Occupational Safety and Health
      issued new rules for personal respirators. All nine new respirator categories are
      authorized in health care facilities for the prevention of the transmission of
      tuberculosis (TB). The new N95 respirator category is the most frequently used
      for this purpose. Data are presented on their efficiency for collecting TB-size
      bacteria and their potential for reaerosolizing collected bacteria. METHODS: All
      measurements of bacterial penetration were performed with dynamic aerosol size
      spectrometers at flow conditions corresponding to normal wear and respirator
      certification conditions. The reaerosolization tests were performed at conditions
      ranging from normal breathing to violent coughing or sneezing. RESULTS: The
      tested N95 respirators collected 0.1 to 0.3 microm particles with efficiencies of
      95% or higher, as specified by the regulations. TB-size bacteria of 0.8 microm
      and larger, however, were collected with 99.5% or higher efficiencies; that is,
      the penetration of these bacteria through the filter material was 0.5% or less,
      much less than the required maximum penetration of 5% for the smaller particle
      sizes. No bacteria were reaerosolized during normal exhalation. Some
      reaerosolization (0.1% or less) was observed only at low humidity and extremely
      high air flow through the respirator, corresponding to violent coughing or
      sneezing. CONCLUSIONS: The filter materials of N95 respirators provide good
      protection against TB bacteria. Thus, a significant number of bacteria can enter
      the respirator-wearer's breathing space only through spaces where the respirator
      inadequately seals to the wearer's face. Reentrainment and reaerosolization of
      mycobacteria is not a problem when normal work practices are observed in health
      care facilities.

PMID- 9584810
TI  - A pseudoepidemic of Alcaligenes xylosoxidans attributable to contaminated saline.
AB  - Alcaligenes xylosoxidans is an uncommon but serious cause of nosocomial
      epidemics. This report describes a cluster of two patients who underwent revision
      of hip arthroplasties and one patient who had a lumbar puncture. Cultures
      obtained during all three procedures showed A. xylosoxidans with similar
      antibiotic sensitivity patterns. An investigation found that saline used to
      process these specimens was contaminated with this organism.

PMID- 9584811
TI  - Aseptics and aesthetics of chlorine bleach: can its use in laundering be safely
      abandoned?
AB  - The disinfecting and cleansing properties of chlorine bleach in high-temperature
      laundering formulations first was demonstrated in 1938, and subsequently was
      found to be equally effective in lower-temperature formulations that included
      modifications in the laundering cycle. Until another well-documented bleaching
      additive becomes commercially available, chlorine bleach should continue to be an
      integral part of the laundering formulations for all textiles used in health care
      facilities.

PMID- 9584812
TI  - Monitoring the efficacy of the sterilizer's cycle and a device's suitability for
      use.

PMID- 9584813
TI  - Soaking endoscopes in 2% glutaraldehyde for 20 minutes: a risk management
      perspective.

PMID- 9584814
TI  - Anticipated reliability of liquid chemical sterilants.

PMID- 9584815
TI  - Significance of antinuclear antibody testing in unexplained second and third
      trimester fetal deaths.
AB  - The purpose of this study was to determine if a group of patients with
      unexplained second or third trimester fetal demise have an increased prevalence
      of antinuclear antibodies (ANA) when compared to controls. During a 5-year period
      from January 1989 through December 1993, the records of all fetal deaths > or =
      500 g or > or = 20 weeks of gestation that occurred at our institution were
      reviewed. In these women the ANA titers were checked at the discretion of the
      physician. The proportion of positive ANA tests in the group of women with
      explained fetal deaths was compared to that in women with unexplained fetal
      deaths. These results were then compared to a control group of healthy gravidas
      presenting to labor and delivery in the third trimester. During this time period,
      848 fetal deaths were recorded. Our study population consisted of 286 patients
      who had an unexplained second or third trimester fetal demise with a record of
      having an ANA drawn. Of the 376 explained fetal deaths, 190 had an ANA assayed.
      The control group included 299 healthy third trimester gravidas. In the group of
      patients with unexplained fetal death, 11.5% (33/286) had a positive ANA, whereas
      16% (31/190) of ANA tests were positive in cases of explained fetal death (P =
      0.17). In the control group, 14% (43/299) had a positive ANA. There were three
      distinct immunofluorescence patterns: nucleolar, speckled, and homogeneous. The
      first two were seen more often in the control group, whereas the latter was seen
      more frequently in those patients with fetal death (P = 0.10). The incidence of a
      significant circulating ANA titer was similar in patients and controls. Moreover,
      there was no significant association between circulating antinuclear antibody
      titers and fetal outcome. More patients with a fetal death had a homogeneous
      nuclear fluorescence pattern when compared to controls; however, this finding was
      not statistically significant. Therefore, we do not recommend routine testing for
      ANA in women with unexplained second or third trimester fetal death.

PMID- 9584816
TI  - Applicability of the third-generation, thyroid-stimulating hormone assay in
      pregnancy.
AB  - Use of the third-generation, thyroid-stimulating hormone (TSH) assay in gravid
      patients has not been validated. We obtained serum from 93 healthy women with a
      singleton gestation and measured TSH using a two-site immunochemiluminescent
      ("sandwich") assay. Standard immunoassays were employed for total T4, free T4,
      and T3 levels. Reference ranges (RR) established by the kit manufacturer were
      used for comparison. Although the mean TSH level for our population was within
      the RR, 12/93 women (13%) had a TSH value below the lower limit of normal. None,
      however, had clinical hyperthyroidism or an elevated free T4. Established RR for
      the third-generation TSH assay may not apply to pregnant women, and isolated TSH
      measurements during pregnancy should be interpreted with caution.

PMID- 9584817
TI  - Does a high carbohydrate preparatory diet affect the 3-hour oral glucose
      tolerance test in pregnancy?
AB  - The aim of this study was to determine the effect of a high carbohydrate
      preparatory diet on the performance of the 3-hour oral glucose tolerance test
      (GTT) in pregnancy. This prospective clinical trial was performed at a university
      hospital outpatient obstetric clinic. Gravidas who had an abnormal blood sugar
      screening test were asked to ingest one of two preparatory diets: > or = 150g/day
      of carbohydrate for 3 days (Carbo) or six Snickers candy bars per day for 3 days
      (Candy), or to remain on their usual diet (Ad lib) prior to the GTT. A 100g oral
      GTT was performed after an overnight fast, and blood glucose values were
      determined at 1, 2, and 3 hours. Patients with either a fasting whole blood
      glucose > 120 mg/dl or > or = two abnormal values on the GTT were considered to
      have gestational diabetes mellitus and received diet therapy. Women who failed
      diet therapy also received insulin. Our primary outcome parameter was the
      intergroup incidence of gestational diabetes mellitus. Other parameters included
      the mean 1-, 2-, and 3-hour glucose values and the rates of both cesarean
      delivery and large-for-gestational age infants. Of the 354 women studied, 108
      entered the Carbo group, 105 entered the Candy group, and 141 comprised the Ad
      Lib group. The three groups were comparable with regard to historic and
      demographic risk factors for gestational diabetes mellitus. After the GTT, 29% of
      the Carbo group were considered to have gestational diabetes mellitus vs. 28% in
      both the Ad lib and Candy groups (P = 0.98). Additionally, both the mean
      intergroup fasting, 1-hour, 2-hour, and 3-hour whole blood glucose values and
      selected clinical outcomes were similar (P = 0.35-0.99). Compared to usual
      dietary intake, recommending a high carbohydrate diet had a negligible effect on
      the 100g oral GTT in pregnancy.

PMID- 9584819
TI  - Congenital pseudohypoaldosteronism presenting in utero with acute polyhydramnios.
AB  - A case of acute polyhydramnios in a fetus with pseudohypoaldosteronism is
      presented. Although rare, metabolic causes for polyhydramnios should be
      considered when no obvious cause is found in workup of the pregnant woman and
      when structural survey of the fetus is normal.

PMID- 9584818
TI  - 72-hour discharge after cesarean delivery: results in a selected Medicaid
      population.
AB  - The purpose of this study was to determine the safety and cost savings of
      discharging low income patients at 72 hours following cesarean delivery.
      Predetermined criteria were used to allow discharge. Selection criteria were no
      medical problems, an afebrile postoperative course, documented bowel function, to
      have tolerated at least one regular meal, and to have reached 72 hours
      postdelivery by 6 o'clock PM at discharge. Each patient returned to clinic 2-3
      days postdischarge for staple removal. Physicians also discharged some low income
      patients home at 72 hours even though strict eligibility criteria were not met.
      Maternal outcome and financial data were compared between patients discharged
      after meeting eligibility criteria versus those who did not. Of 1,299 cesareans
      performed from July 1, 1993-July 31, 1995, 906 (70%) were performed in low income
      patients and 399 (44%) of these women were discharged at 72 hours. Twenty-seven
      women were lost to follow-up and 286 (77%; Group A) met the eligibility criteria
      for 72-hour discharge. Eighty-six women (23%; Group B) who did not meet criteria
      were also discharged at 72 hours. When maternal outcome data from the two groups
      were compared, Group B patients (did not meet criteria) were more likely to have
      been readmitted at < or = 30 days (7 of 86; 8% vs. 8 of 286; 3%; P = 0.05) and
      had longer hospital stays (27 days vs. 22 days) than Group A patients (met
      criteria). Net cost savings in 2 years was $448 per discharge for Group A, but
      only $333 per discharge for Group B. In our selective 72-hour discharge program,
      failure to abide by predetermined guidelines established to select only low risk,
      afebrile patients for 72-hour discharge resulted in more hospital readmissions,
      and longer stays and thus was not as cost effective.

PMID- 9584820
TI  - Hemodynamic patterns in preterm and term labor: working hypothesis.
AB  - This report describes hemodynamic patterns recorded from patients who had
      spontaneous abortion, preterm, and term labor. A working hypothesis theorizes
      that specific patterns observed in these situations can be identified and
      correlated with those present in the preovulatory and postovulatory phases of the
      menstrual cycle and thereby provide a clue to endocrine imbalances that may occur
      during pregnancy and play a role in the pathophysiology of these complications.

PMID- 9584821
TI  - Interpregnancy weight retention patterning in women who breastfed.
AB  - This study compares weight change in lactating women with an 18-month
      interpregnancy interval with woman who also breastfed but did not have an
      immediate subsequent pregnancy. Cases were women who breastfed an index infant
      for 6 months and subsequently became pregnant within 18 months (cases = 25), and
      the controls also breastfed an index infant for 6 months but had no ensuing
      pregnancy (controls = 20) within 18 months. The pattern of postpartum weight
      retention following the initial pregnancy was not statistically different in
      cases compared to the controls. However, following their ensuing subsequent
      pregnancy, cases were 1.3 kg heavier than their average weight after their
      baseline pregnancy (P = 0.02). The best predictor of this greater weight was
      their weight change during the interpregnancy interval (P = 0.03). Total weight
      gain during the gestational period of the subsequent pregnancy was not associated
      with the greater weight following the subsequent pregnancy. Likewise, estimates
      of the amount of energy as calories or physical activity levels were not
      significant predictors of this greater weight following the subsequent pregnancy.
      These findings suggest that monitoring of postpartum weight, even in
      breastfeeding women, is essential. These findings indicate that breastfeeding
      women begin the next postpartum interval weighing more than the amount observed
      in the initial postpartum period.

PMID- 9584822
TI  - Working hypothesis relative to the hemodynamics of menstruation and pregnancy.
AB  - A working hypothesis relative to detailed hemodynamic changes that occur during
      menstruation and pregnancy theorizes that the marked biophysical similarities
      existing between the postovulatory phase of the menstrual cycle and the latter
      half of pregnancy are endocrine based. The data are acquired with apparatus that
      records cutaneous pressure pulses and the maternal electrocardiogram, which
      together provide the basis for deriving the determinants of mean arterial
      pressure.

PMID- 9584823
TI  - Effects of placental delivery method and intraoperative glove changing on
      postcesarean febrile morbidity.
AB  - This study was designed to evaluate the effects of the placental delivery methods
      and intraoperative glove changing on postcesarean febrile morbidity. In this
      randomized controlled trial, consenting patients were randomized to one of four
      management protocols: Group A (n = 26)--no glove change with manual placental
      delivery; Group B (n = 27)--no glove change with expressed placental delivery;
      Group C (n = 27)--glove change with manual placental delivery; and Group D (n =
      28)--glove change with expressed placental delivery. Glove change was performed
      by removal of a second glove after delivery of the fetal head. Variables examined
      included febrile morbidity, endometritis, maximums and durations of elevated
      temperatures, as well as other demographic, intrapartum, and postpartum
      variables. Febrile morbidity and endometritis rates were not significantly
      different between the four groups. When the groups were combined so as to compare
      no glove change versus glove change (Groups A and B vs. C and D) and manual
      versus expressed placental delivery (Groups A and C vs. B and D), there were no
      significant differences in either febrile morbidity (relative risk: 0.7, 95% CI:
      0.3-1.4 and relative risk: 1.4, 95% CI: 0.6-3.5) or endometritis (relative risk:
      1.2, 95% CI: 0.5-2.8 and relative risk: 1.5, 95% CI: 0.6-3.6), respectively.
      There were no statistically significant differences in measures of postcesarean
      febrile morbidity based on placental delivery method or intraoperative glove
      change.

PMID- 9584824
TI  - An ELISA technique for quantitation of human xenoantibodies binding to pig cells:
      application in patients with pig kidneys extracorporeally connected to the
      circulation.
AB  - A quantitative ELISA technique for determination of human anti-pig xenoantibody
      number in serum samples has been established using pig lymphocytes and pig/rabbit
      erythrocytes as target cells and a pool of serum from human blood group AB
      donors. The number of low affinity antibodies binding to the cells was determined
      by quantitation following the use of aqueous washing of the cells and separation
      of bound and unbound antibodies with the phthalate oil method. The efficiency of
      different soluble Gal(alpha)1-3Gal-terminating di- and tri-saccharides to inhibit
      antibody binding was tested and found to vary between 70-90% at a saccharide
      concentration of 10 mg/ml. The assay was used to evaluate the antibody changes in
      two patients who, after plasmapheresis treatments, had pig kidneys
      extracorporeally connected to their blood circulation. The number of anti-pig
      IgM/IgG antibodies bound to each pig lymphocyte were reduced from 5,600/13,200 to
      1,300/3,100 in patient 1 and from 1,200/6,500 to 500/2,100 in patient 2 by three
      consecutive daily plasmapheresis treatments. Although the lymphocytotoxic titers
      were reduced to very low levels, the antibody numbers still present in the blood
      of patient 1 caused a hyperacute rejection of the pig kidney. However, the
      antibody levels in patient 2 did not cause rejection of this kidney during 15 min
      perfusion time. A strong anti-pig antibody response 3 weeks after the perfusion
      experiment was found in patient 1 as shown by 27,600/245,300 IgM/IgG molecules
      bound to pig lymphocytes corresponding to an increase of lymphocytotoxic titer
      from 8 to 512. The second patient showed a much weaker immune response with
      1,400/19,800 IgM/IgG antibodies corresponding to a lymphocytotoxic titer increase
      from 8 to 32. The use of this quantitation technique enables more accurate
      investigation of antibody binding to xenogenic target cells than conventional
      titration techniques.

PMID- 9584825
TI  - Characterisation of human natural anti-sheep xenoantibodies.
AB  - Currently, the pig species is regarded as the most likely organ donor for human
      xenotransplantation in the future. However, it cannot be granted that the pig
      will be the optimal species of choice. We have studied human anti-sheep
      antibodies in comparison with anti-pig antibodies. The anti-sheep lymphocytotoxic
      and hemagglutination titers were in the range 8 to 128 and 2 to 32, respectively,
      in single individuals, which were considerably lower than the anti-pig titers of
      these individuals. Perfusion of sheep kidneys with human blood reduced the anti
      sheep xenoantibody titers to zero as measured by lymphocytotoxic,
      hemagglutination, and sheep aortic endothelial cell antibody binding assays. The
      perfused kidneys showed generalised depositions of human IgM and C3c in the
      vascular tree and focal depositions of C1q and fibrin. Obliteration of
      capillaries by human platelets and polymorphonuclear cells were observed. Total
      neutral glycolipid fractions were isolated from sheep intestinal, pancreatic, and
      kidney tissues. By using a chromatogram binding assay, a monoclonal anti-Forssman
      antibody identified a single compound with five sugar residues in all organs.
      Several glycolipid bands were stained in all organs by the Gal(alpha)1-specific
      lectin I-B4 from Griffonia (Bandeiraea) Simplicifolia. A human AB serum pool
      showed staining by both IgG and IgM antibodies of the Forssman and Gal(alpha)1
      terminating components as well as some other, not structurally identified,
      components. The Forssman and Gal(alpha)1-reactivity in human sera could be
      eliminated by immunoadsorption using Forssman and Gal(alpha)1-3Gal
      immunoadsorbent columns, respectively. Immunostaining of sheep kidney tissue
      sections showed the presence of Gal(alpha)1-terminating epitopes by
      immunoperoxidase and immunogold silver staining techniques. Proximal convoluted
      tubules showed a strong staining, while thin loops of Henle, collecting ducts,
      urothelium, and vessels showed a weaker staining. Distal convoluted tubules and
      thick loops of Henle were completely negative. In summary, human serum contains
      anti-sheep xenoantibodies reacting mainly with the Forssman and Gal(alpha)1
      determinants in sheep tissues and the anti-sheep antibody titers are lower than
      the corresponding anti-pig titers.

PMID- 9584826
TI  - Depletion of anti-Gal(alpha)1-3Gal antibody in baboons by specific alpha-Gal
      immunoaffinity columns.
AB  - Ongoing studies at our center on facilitating transplantation of discordant
      xenogeneic organs are focused on tolerance induction. To abrogate hyperacute
      rejection, we have used adsorption methods to eliminate natural anti-Gal(alpha)1
      3Gal (alphaGal) antibodies from the circulation of baboons. We have analyzed data
      concerning antibody removal in baboons that were 1) immunologically naive, 2)
      receiving conventional pharmacologic immunosuppressive therapy (IS), and 3)
      treated with a conditioning regimen for tolerance induction. We compared the
      efficiency of removing alphaGal antibody 1) by perfusion of whole blood through
      an alphaGal affinity column (CP; n=5) with 2) perfusion of plasma (separated from
      cellular components by apheresis) through an alphaGal column (CPA; n=39). Our
      studies demonstrate that 1) CP and CPA are equally effective in removing anti
      alphaGal antibody, 2) CPA is the method of choice if multiple adsorptions are
      required, 3) CPA in naive animals transiently affects levels of total IgG and
      IgM, 4) four CPAs repeated at 2-4 day intervals in association with heavy IS
      reduce the pool of anti-alphaGal antibody and total Ig, and 5) splenectomy and/or
      IS delay the return of anti-alphaGal antibody.

PMID- 9584827
TI  - Human NK cell and ADCC reactivity against xenogeneic porcine target cells
      including fetal porcine islet cells.
AB  - In vitro studies of human NK cell-mediated cytotoxicity and ADCC against porcine
      target cells were performed. Stimulation of human PBMC responder cells with
      either allogeneic or xenogeneic porcine cells led to a marked increase in NK cell
      reactivity. Maximum reactivity was reached following 3-6 days of in vitro
      culture. The sensitivity of target cells ranked as follows: K562 > porcine PHA
      induced lymphoblasts > resting porcine PBMC. Limiting dilution analysis showed
      that allo- and xeno-stimulation in vitro led to differentiation of similar
      frequencies of effector NK cells. Split culture experiments showed that single NK
      effector cells were cytotoxic against both K562 and porcine lymphoblasts,
      demonstrating that individual NK cells lack species specificity. NK effector cell
      generation stimulated by xenogeneic cells was cyclosporin A (CsA) sensitive and
      dependent on the presence of autologous responder T lymphocytes, a dependence
      that was completely reconstituted by the sole addition of human IL-2.
      Xenostimulation of enriched CD3+ cells also led to a preferential appearance of
      CD16+ or CD56+ lymphoblasts. Natural xenoreactive human anti-porcine antibodies
      are mainly of IgM and IgG2 subclasses, but antibodies in xenoimmunised patients
      reactive against porcine lymphocytes and fetal porcine islet cells were also of
      IgG1 and IgG3 subclasses. The same subclass distribution was found among
      antibodies specific for gal(alpha)1,3 gal epitopes as shown by tests performed
      with alpha1,3 galactosyltransferase-transfected Raji cells (human Burkitt
      lymphoma cells). Natural antibodies did not mediate ADCC, whereas gal(alpha)1,3
      gal-specific antibodies in sera from xenoimmunised patients did. Fetal porcine
      islet cells were sensitive to human NK cell-mediated cytotoxicity and to ADCC
      mediated by xenoimmune sera.

PMID- 9584829
TI  - Long-term survival of hamster islet xenografts in mice under short-course
      treatment with nondepleting versus depleting anti-CD4 monoclonal antibodies.
AB  - Xenogeneic grafts provide a potential alternative to the current shortage of
      human organs for transplantation. However, the prevention of rejection and
      tolerance induction of xenografts still remain to be further explored. Islet
      xenografts appear more promising than vascularized whole organ xenografts and
      additionally also more resistant to the recurrence of autoimmune disease than
      allografts. Recently, the nondepleting monoclonal antibody (mAb), which blocks
      the CD4 molecule on lymphocytes, was reported to be able to induce tolerance in
      allotransplantation and CD4 positive cells were further confirmed to be a major
      factor responsible for cellular xenograft rejection. Therefore, we hypothesize
      that anti-CD4 nondepleting mAb could also be effective in protecting cellular
      xenografts and inducing unresponsiveness of recipients. We studied the effect of
      the nondepleting anti-CD4 mAb YTS177.9 on islet xenograft survival by using the
      hamster-to-mouse islet transplantation model. Results were compared with that of
      the depleting anti-CD4 mAb GK1.5 that was shown to have similar binding sites on
      the CD4 molecule to mAb YTS177.9. Our data show that mAb YTS177.9 did effectively
      prolong the survival of islet xenografts and, in addition, also successfully did
      induce long-term acceptance of 40% grafts after only three perioperative
      injections of 0.5 mg mAb per mouse. The average survival of the graft was
      markedly prolonged to >66.8+/-37.1 days compared with controls (8.3+/-1.4 days)
      or with the depleting anti-CD4 mAb GK1.5 (25.7+/-5.5 days). However, the latter
      displayed a more profound inhibition in in vitro and ex vivo mixed lymphocyte
      xenoreaction than mAb YTS177.9. Moreover, the activity of this nondepleting mAb
      was found to be dose-dependent and 80% of grafts survived permanently when the
      dose was increased to six injections of 0.5 mg mAb. Like mAb GK1.5, mAb YTS177.9
      also prevented rejection when given after a delay of two days posttransplant. In
      addition, we found that neither depleting nor nondepleting anti-CD8 mAb was
      effective in this model. Our results strongly suggest that an anti-CD4
      nondepleting or blocking mAb alone is able to induce long-term acceptance of
      islet xenografts and that blocking the CD4 molecule is significantly superior to
      depleting CD4 positive cells for the protection of islet xenografts. This may
      indicate that CD4 cells play a major role in xenograft tolerance induction.

PMID- 9584828
TI  - Adoptive transfer: the role of perforin in mouse cytotoxic T lymphocyte rejection
      of human tumor xenografts in vivo.
AB  - The popliteal lymph node cells of immunocompetent mice generated a strong in
      vitro cytotoxic response to footpad injection of several human tumor cell lines
      and the resulting mouse effector cells predominantly used a perforin-mediated
      cytotoxic mechanism. A relatively minor FasL-dependent cytotoxic response to CEM
      CCRF and Jurkat leukemias, but not colon carcinoma COLO 205 cells, was also
      detected in immunized perforin-deficient mice. In vitro depletion of CD3+ CD8+ T
      cells, but not CD4+ T or NK1.1+ cells, completely inhibited lysis of human tumor
      cells, suggesting that CD3+ CD8+ T cells were effectors of perforin-mediated
      xenospecific cytotoxicity. Xenospecific cytotoxic T cells from wild-type mice
      were extremely efficient at rejecting tumor when adoptively transferred into scid
      mice bearing established COLO 205, CEM-CCRF, or Jurkat tumor xenografts. By
      contrast, cytotoxic T lymphocytes of perforin-deficient mice had no effect on the
      growth of established tumor xenografts. These data indicate that perforin, and
      hence direct cytotoxicity, plays a key role in the ability of adoptively
      transferred CD8+ cytotoxic T lymphocytes to eradicate established xenografts.

PMID- 9584830
TI  - Literature update 1997, part 3.

PMID- 9584831
TI  - The long (Gs(alpha)-L) and short (Gs(alpha)-S) variants of the stimulatory
      guanine nucleotide-binding protein. Do they behave in an identical way?
AB  - The relative proportions and tissue distribution of the long (Gs[alpha]-L) and
      short (Gs[alpha]-S) variants of the a subunit of the stimulatory G-protein
      (Gs[alpha]) change under a wide range of metabolic conditions, such as cellular
      differentiation, ontogenetic development, ageing and various adaptive processes.
      Although the two variants of Gs(alpha) are generally regarded to be functionally
      identical, this review summarizes recent experimental support for the non
      identical behaviour of these proteins. Similarly, there is no consistent evidence
      for the functional meaning of these changes as far as regulation of adenylate
      cyclase activity is concerned. Since it is hard to believe that the complicated
      scheme of alternative splicing and the energy-consuming synthesis of proteins
      would be performed for no reason, it is suggested that Gs[alpha] variants might
      be involved in controlling other effector molecules and processes besides
      adenylate cyclase and cAMP metabolism. Such an idea is indirectly supported by
      specific alterations in the Gs[alpha]-L/Gs[alpha]-S ratio under various
      physiological and pathophysiological conditions.

PMID- 9584832
TI  - Is prolactin a gonadotrophic hormone in red deer (Cervus elaphus)? Pattern of
      expression of the prolactin receptor gene in the testis and epididymis.
AB  - This study investigated the pattern and site of expression of the prolactin
      receptor gene in the testis and epididymis of red deer collected during the
      breeding season (n=3). Ribonuclease protection assays using 50 microg total RNA
      and a 300 bp [32P]-labelled antisense cRNA probe, generated from the
      extracellular domain of the red deer prolactin receptor, confirmed the expression
      of the receptor in both the testis and epididymis; a higher level of prolactin
      receptor mRNA was detected in the epididymis compared with the testis (170.4+/
      1.5 x 10(3) and 26.3+/-2.7 x 10(3) arbitrary units respectively; P<0.05). In situ
      hybridisation using 300 bp [33P]-labelled sense and antisense cRNA probes
      generated from the extracellular domain of the receptor localised the expression
      sites to the seminiferous tubules and interstitial compartments of the testis and
      the epithelial layer of the epididymal duct. Quantification of grain numbers
      demonstrated a higher level of expression of the receptor in the epididymis
      compared with the interstitial and seminiferous tubule compartments of the testis
      (18.1+/-4.4 x 10(2), 10.1+/-2.0 x 10(2) and 8.3+/-0.8 x 10(2) grains/microm2
      respectively; P<0.05). However, no differences were detected in the level of
      expression of the receptor between the interstitial and seminiferous tubule
      compartments of the testis. Immunocytochemistry using an anti-prolactin receptor
      antibody, raised against a peptide sequence from the extracellular domain of the
      rat prolactin receptor, localised expression of the receptor gene to the Leydig
      cells, pachytene spermatocytes, round spermatids and elongating spermatids. In
      the epididymis, the receptor was localised to the epithelial layer within the
      epididymal ducts. Expression of the prolactin receptor gene in the red deer
      testis and epididymis suggests a role for the hormone in steroidogenesis and
      spermatogenesis.

PMID- 9584833
TI  - Transcriptional activity of the hamster CYP11B2 promoter in NCI-H295 cells
      stimulated by angiotensin II, potassium, forskolin and bisindolylmaleimide.
AB  - We studied the regulation of the hamster CYP11B2 gene in the NCI-H295 cell line,
      which is known to produce aldosterone in response to stimulation by angiotensin
      II (AII) and KCl. Ten deletion plasmids harboring the 5'-untranslated region of
      the CYP11B2 gene were used for chloramphenicol acetyltransferase (CAT) assays.
      Transient transfections showed progressively increasing basal promoter activity
      by constructs beyond the TATA box, with a peak occurring with the -167 bp
      construct which contains putative Adl, Ad2, Ad5 and the newly reported -143/-161
      cis-element sequences. The promoter activity was lower with the construct
      containing the putative Ad3 cis-element and increased with longer constructs.
      This indicates the presence of both inhibitory and stimulatory cis-elements in
      this area of the gene. Expression of the reporter gene of all constructs was
      stimulated by AII and KCl, with the exception of the construct containing only
      the TATA box, which showed 6-fold and 10-fold increases occurring with the -167
      bp deletion plasmid. The patterns of increase in CAT activity with AII and KCI
      treatment were similar, showing that these two regulators can stimulate hamster
      CYP11B2 promoter activity through common cis-elements. The calcium channel
      antagonist nifedipine blocked the stimulatory effects of KCl on CAT activity,
      showing the involvement of calcium channels in the regulation of CYP11B2 gene
      transcription by KCl. 12-O-Tetradecanoylphorbol 13-acetate, a known stimulator of
      the protein kinase C (PKC) signaling pathway, was without significant effect on
      CAT activity. Bisindolylmaleimide, a specific inhibitor of PKC, had a significant
      enhancing effect (3.4- to 6-fold), indicating that PKC may negatively regulate
      the expression of the hamster CYP11B2 gene in NCI-H295 cells. A mutation was
      induced in the sequence -143/-161 of the - 350 bp construct in order to determine
      its importance in the regulation of hamster CYP11B2 promoter activity. The
      stimulatory effects of AII, KCl, forskolin and bisindolylmaleimide on CAT
      activity were significantly less in the mutant than in the wild type. These
      results confirm that this cis-element is necessary in maintaining a high level of
      transcriptional activity in stimulated NCI-295H cells. In conclusion, using NCI
      295H transfected cells, we have found that the 5'-untranslated region of the
      hamster CYP11B2 gene possesses transcriptional activity with stimulatory and also
      inhibitory cis-elements; CYP11B2 promoter activity can be stimulated by AII, KCl,
      forskolin, dibutyryl cAMP and bisindolylmaleimide. Our results suggest that this
      gene is positively regulated through the protein kinase A signaling pathway and
      through calcium channels, whereas PKC may have a negative regulatory effect upon
      the transcription of the CYP11B2 gene. Furthermore, we have shown that the cis
      element -143/-161 in the 5'-untranslated region of the hamster CYP11B2 gene is
      important in maintaining a high level of promoter activity in stimulated NCI-295H
      cells.

PMID- 9584834
TI  - Differential expression of genes for aromatase and estrogen receptor during the
      gonadal development in chicken embryos.
AB  - In birds, differentiation of embryonic gonads is not as strictly determined by
      the genetic sex as it is in mammals, and can be influenced by early manipulation
      with a sex steroid hormone. Thus administration of an aromatase inhibitor induces
      testis development in the genetic female, and administration of estrogen induces
      a left ovotestis in the genetic male embryo. Another feature of avian
      gonadogenesis is that only the left ovary develops in most species. Molecular
      mechanisms underlying these features at the level of gene expression have not
      been elucidated. In this paper, we present evidence that a gene for aromatase
      cytochrome P-450, an enzyme required for the last step in the synthesis of
      estradiol-17beta, is expressed in medullae of the left and right gonads of a
      female chicken embryo, but not in those of a male chicken embryo, and that an
      estrogen receptor gene is expressed only in epithelium (and cortex later, in the
      female) of the left, not the right, gonad of both sexes, but the expression in
      the male left gonad is temporary and restricted to an early stage of development.
      Differential expression of these two genes serves well to explain the above
      features of gonadal development in birds. Furthermore, in ovo administration of
      estradiol-17beta from the 5th to the 14th day of incubation does not cause
      expression of the estrogen receptor gene in the right gonad of chicken embryos of
      either sex, suggesting that the absence of expression of the estrogen receptor
      gene in the right gonad is not the result of down-regulation, but may be regarded
      as an important cause of the unilateral ovarian development.

PMID- 9584836
TI  - Detection of estrogen receptor alpha, carbonic anhydrase II and tartrate
      resistant acid phosphatase mRNAs in putative mononuclear osteoclast precursor
      cells of neonatal rats by fluorescence in situ hybridization.
AB  - Increasing evidence suggests that estrogen deficiency in women promotes the
      expansion of populations of bone marrow cells that differentiate into osteoclasts
      under the influence of osteotropic hormones and local factors. A progressive
      cytoplasmic accumulation of osteoclastic bone resorbing enzymes, such as tartrate
      resistant acid phosphatase (TRACP) and carbonic anhydrase II (CA II),
      characterizes osteoclast differentiation. To evaluate the possibility that
      estrogen may have a direct effect on osteoclast precursor cells, we investigated
      the mRNA levels of estrogen receptor a (ERa), TRACP and CA II genes in neonatal
      rat bone imprints by fluorescence in situ hybridization and confocal microscopy.
      Morphological assessment of bone imprints has shown that the putative mononuclear
      osteoclast precursor cells (MOPC) display strongly basophilic cytoplasm and a low
      nuclear/cytoplasmic ratio, while some of these cells possess pale-staining
      ruffled border regions similar to those observed in osteoclasts. Both CA II and
      TRACP mRNAs were detected in putative MOPC as well as multinuclear osteoclasts.
      The gene transcripts were mainly located in the cytoplasm of these cells. To
      determine whether these putative MOPC possess ER mRNA, a 637 base pair antisense
      ER riboprobe was used. The results indicated that MOPC which show TRACP
      reactivity express high levels of ER gene transcripts in their cytoplasm. In
      contrast, only a few multinuclear osteoclasts in the bone imprints possessed ER
      gene transcripts. Interestingly, the levels of ER mRNA in these multinuclear
      osteoclasts were very low compared with those in the putative MOPC. Treatment
      with RNase prior to hybridization resulted in a significant loss of signal in
      these cells. The results of these studies suggest that estrogen may have a direct
      role in modulating the recruitment of osteoclast precursor cells during
      osteoclastogenesis.

PMID- 9584835
TI  - Selenoprotein expression and brain development in preweanling selenium- and
      iodine-deficient rats.
AB  - Selenium deficiency causes further impairment of thyroid hormone metabolism in
      iodine-deficient rats and therefore could have a role in the aetiology of both
      myxoedematous and neurological cretinism in humans. Thyroidal type I
      iodothyronine deiodinase (ID-I), cytosolic glutathione peroxidase and
      phospholipid hydroperoxide glutathione peroxidase activities were increased in
      iodine-deficient adult rats and their offspring at 11 days of age. Thyroidal ID-I
      activity was unchanged and thyroidal cytosolic glutathione peroxidase activity
      was decreased by more than 75% by combined selenium and iodine deficiency in 11
      day-old rats, indicating that, while the thyroid retained an ability to produce
      3,3',5-triiodothyronine (T3), the gland was probably more susceptible to
      peroxidative damage caused by increased hydrogen peroxide concentrations driven
      by increased thyrotrophin. Thyroidal atrophy, common in myxoedematous cretinism,
      did not occur in iodine- or selenium and iodine-deficient rat pups. Iodine
      deficiency increased brain type II iodothyronine deiodinase activity 1.5-fold in
      4-day-old rats and 3-fold in 11-day-old rats, regardless of selenium status. Thus
      rats were able to activate compensatory mechanisms in brain that would maintain
      T3 concentrations in selenium and iodine deficiencies. Surprisingly, however,
      selenium deficiency had a greater effect than iodine deficiency on markers of
      brain development in rat pups. Expression of the brain-derived neurotrophic
      factor (BDNF) mRNA was decreased in selenium deficiency in 4- and 11-day-old pups
      and in combined selenium and iodine deficiency in 4-day-old pups. Iodine
      deficiency caused an increase in BDNF expression in 11-day-old pups but had no
      effect on 4-day-old pups. Myelin basic protein mRNA expression in brain was
      decreased by combined selenium and iodine deficiency in 11-day-old rats.

PMID- 9584837
TI  - Tumour necrosis factor-alpha stimulates increased expression of prostaglandin
      endoperoxide H synthase Type 2 mRNA in amnion-derived WISH cells.
AB  - We have evaluated the mechanism by which tumour necrosis factor-alpha (TNF-alpha)
      induces increased prostaglandin (PG) biosynthesis in amnion-derived WISH cells.
      WISH cells were treated with 50 ng/ml TNF-alpha or vehicle for 0-24 h. PGE2
      production was stimulated by TNF-alpha within 2 h and continued to accumulate for
      at least 24 h. Increased prostaglandin endoperoxide H synthase (PGHS)-2 mRNA
      expression was evident within 30 min and was highest by 1 h, returning to
      unstimulated levels by 2 h. The PGHS-2 mRNA was re-induced at 8 h and was also
      elevated at 16 h. Immunoreactive PGHS-2 protein was nearly undetectable in
      control cells. However, within 30 min of TNF-alpha treatment, PGHS-2 protein was
      elevated and was induced for at least 16 h suggesting rapid production of both
      the PGHS-2 mRNA and protein. Transcription run-on assays indicated that the
      initial increase in the PGHS-2 mRNA was due to a 20-fold increase in the rate of
      transcription. The PGHS-2 mRNA decayed with an apparent half-life of 1 h in TNF
      alpha-stimulated WISH cells. Induction of PGHS-2 expression proceeded in the
      presence of 10 microg/ml cycloheximide which agrees with the classification of
      PGHS-2 as an immediate early gene. These results indicate that a bi-phasic
      induction of the PGHS-2 mRNA is due, in part, to an initial transcriptional
      activation which results in rapid and continued synthesis of the PGHS-2 protein.
      This may be a unique characteristic of amnion cells which may be partially
      responsible for increased PG concentrations in the amniotic fluid during
      infection-associated preterm labour.

PMID- 9584838
TI  - Binding characteristics of antibodies to the TSH receptor.
AB  - We have used fragments of the TSH receptor (TSHR) expressed in E. coli as
      glutathione S-transferase fusion proteins to produce rabbit polyclonal antibodies
      and a panel (n=5) of monoclonal antibodies to the extracellular fragment of the
      TSHR. The binding characteristics of the antibodies to linear, conformational,
      glycosylated and unglycosylated forms of the receptor in different assay systems
      have been investigated. The reactivity of these antibodies with the TSHR was
      assessed by Western blotting with both native and recombinant human TSHR
      expressed in CHO cells, immunoprecipitation of 35S-labelled full-length TSHR
      produced in an in vitro transcription/ translation system, immunoprecipitation of
      125I-TSH/TSHR complexes, inhibition of 125I-TSH binding to the TSHR and
      fluorescence activated cell sorter (FACS) analysis of binding to CHO-K1 cells
      expressing the TSHR on their cell surface. Fab fragments of monoclonal antibodies
      were isolated, labelled with 125I and used to determine the affinity constants of
      these antibodies with receptor, bound and free Fab being separated by
      polyethylene glycol (PEG) precipitation. Rabbit polyclonal and mouse monoclonal
      antibodies reacted with the TSHR in Western blotting and one monoclonal antibody
      (3C7) was able to inhibit 125I-TSH binding to native human TSHR (74% inhibition),
      recombinant human TSHR (84% inhibition) and porcine TSHR (65% inhibition).
      Affinity constant values for TSHR monoclonal antibody Fab fragments calculated
      using Scatchard analysis were about 10(7) M(-1). Four out of five monoclonal
      antibodies reacted in FACS analysis with TSHR expressed on the surface of CHO-K1
      cells. The FACS unreactive monoclonal (3C7) bound well to detergent solubilised
      TSH receptors and this emphasised the importance of using a combination of FACS
      analysis and radioactively-labelled probes in analysis of the TSH receptor. The
      monoclonal antibodies produced in this study were found to be of relatively low
      affinity but proved useful for detection of the receptor by Western blotting and
      by FACS analysis.

PMID- 9584839
TI  - Modulation of mouse estrogen receptor transcription activity by protein kinase C
      delta.
AB  - The effect of protein kinase C (PKC) delta on the transcriptional activity of the
      mouse estrogen receptor was investigated. The receptor was expressed transiently
      in Cos-1 and NIH3T3 cells in the presence of wild-type, dominant negative or
      constitutively active forms of PKC delta. Transfection experiments demonstrated
      that PKC delta stimulated both unliganded and liganded estrogen receptor
      transcriptional activity. This stimulatory effect was not observed using PKC
      alpha or PKC epsilon. 4-Hydroxytamoxifen and the pure anti-estrogen ICI 164,384
      reduced receptor transcriptional activity in the presence of PKC delta. The
      stimulatory effect of PKC delta on estrogen receptor transcriptional activity was
      mediated by the N-terminal activation function 1 (AF-1) domain. The reduced
      stimulatory effect of PKC delta on transcriptional activity of the
      phosphorylation defective mutant of estrogen receptor suggests that
      phosphorylation of serine 122 in the AF-1 region may mediate the modulatory
      effect of PKC delta. Wild-type PKC delta caused a twofold increase in estrogen
      receptor phosphorylation, while a dominant negative mutant of PKC delta reduced
      the receptor phosphorylation to five percent of that caused by wild-type PKC
      delta. Our results suggest that PKC delta participates in the signaling pathways
      that lead to estrogen receptor phosphorylation and its effect on estrogen
      receptor transcriptional activation is both cell type and promoter specific.

PMID- 9584840
TI  - Beta2-adrenoceptor desensitization in non-pregnant estrogen-primed rat myometrium
      involves modulation of oxytocin receptor gene expression.
AB  - The nona-peptide oxytocin (OT) induces contraction of the myometrium by
      interaction with specific plasma membrane associated OT receptors (OTR), whereas
      stimulation of beta2-adrenoceptors (beta2AR) causes relaxation. Homologous
      desensitization of the myometrium to both hormones has been described. However, a
      possible interaction between the two systems has not been investigated. In the
      present study, long-term in vivo treatment of non-pregnant estrogen-primed rats
      with isoproterenol decreased maximal relaxation of isolated uterine strips
      challenged with isoproterenol. Increased EC50 values of similarly treated animals
      suggest that the coupling between receptor occupancy and contractile response was
      impaired. Since beta2AR mRNA levels were left unchanged, we conclude that the
      homologous desensitization to beta2 stimulation is not due to changes in beta2AR
      gene expression. OT infusion did not alter beta2AR mRNA levels or isoproterenol
      induced relaxation of isolated uterine strips. Treatment with OT had no effect on
      the amount of myometrial OTR mRNA. We have previously found that OT down
      regulates OTR in the non-pregnant rat myometrium, but this therefore does not
      appear to take place at the level of mRNA production. Isoproterenol treatment
      resulted in a three-fold increase in OTR mRNA. This was accompanied by a 91% rise
      in OTR binding and an augmented contractile response of isolated uterine strips
      to OT, suggesting that the increased production of mRNA reflects formation of
      active receptors. Neither OTR affinity nor EC50 of in vitro strips was affected
      by isoproterenol treatment. We conclude that stimulation of beta2AR causes
      heterologous up-regulation of OTR in the non-pregnant estrogen-primed rat
      myometrium.

PMID- 9584841
TI  - Cloning of bovine parathyroid hormone-related protein (PTHrP) cDNA and expression
      of PTHrP mRNA in the bovine mammary gland.
AB  - Parathyroid hormone-related protein (PTHrP) produced by the mammary gland has
      been postulated to have multiple functions in both the mother and neonate. In
      humans, alternative 3'-mRNA splicing and endoproteolytic processing result in
      multiple bioactive PTHrP peptides. Multiple PTHrP peptides also have been
      reported in bovine milk. To investigate the source of molecular heterogeneity of
      PTHrP in bovine milk, bovine PTHrP was cloned from a bovine brain cDNA library,
      sequenced and used to characterize the mammary PTHrP transcript. A 1065 bp clone
      (bP1) for bovine PTHrP was isolated from a brain cDNA library. The bP1 clone
      contained the entire coding sequence of PTHrP and 61 and 473 nucleotides of the
      5'- and 3'-untranslated regions (UTRs) respectively. The predicted amino acid
      sequence of bovine PTHrP was 72-92% homologous to the sequences of chicken, rat,
      mouse, human, and canine PTHrP with the highest sequence divergence present in
      the C-terminal region of the peptide. The 5'- and 3'-UTRs of bovine brain PTHrP
      have a high degree of homology to exons 4 and 9 of human PTHrP respectively.
      PTHrP was expressed as a single 1200 nucleotide mRNA transcript in lactating
      bovine mammary tissue. RT-PCR using region-specific oligonucleotide primers
      derived from bP1 demonstrated that PTHrP mRNA transcripts in bovine brain and
      lactating mammary gland utilize the same 5'- and 3'-UTRs. Expression of PTHrP
      mRNA was localized to secretory and ductular epithelial cells within the
      lactating mammary gland, as detected using in situ hybridization. Expression of
      PTHrP mRNA was demonstrated in the mammary gland during late pregnancy and
      throughout lactation in cows.

PMID- 9584842
TI  - Influence of acute elevation of plasma AVP level on rat vasopressin V2 receptor
      and aquaporin-2 mRNA expression.
AB  - It is known that vasopressin V2 receptor (V2R) mRNA is downregulated by elevated
      plasma arginine vasopressin (AVP) following chronic osmotic stimulation. To
      elucidate the response in V2R mRNA expression to acute elevation of the plasma
      AVP level, we investigated the time-course change of rat V2R mRNA expression
      after subcutaneous injection of AVP (10 microg/body). Plasma AVP levels increased
      from 1.4+/-0.3 pg/ml to 56.8+/-10.7 pg/ml by an hour after injection,and returned
      to the control level at 6 h. By Northern blotanalysis, V2R mRNA expression
      decreased to 52.7+/-3.7% of the control level at 2 h, and then returned to the
      control level by 6 h. Furthermore we investigated the time-course change of
      aquaporin-2 (AQP2) mRNA expression. AQP2 mRNA expression increased gradually
      after injection and reached 240.3+/-7.5% of the control level at 6 h. Then it
      returned to the control level. This study showed that the downregulation of V2R
      mRNA occurred rapidly after acute elevation of the plasma AVP level, and AQP2
      mRNA expression was upregulated despite the downregulation of V2R mRNA.

PMID- 9584843
TI  - Establishment of a stable steroidogenic porcine granulosa cell line.
AB  - We report the establishment and preliminary characterization of a stable
      steroidogenic granulosa cell line, JC-410. This cell line was obtained by
      spontaneous immortalization of a primary culture of porcine granulosa cells.
      Cultured JC-410 cells produced less progesterone than granulosa cells in primary
      culture. Progesterone synthesis by JC-410 cells was approximately 10% and 1% of
      the amount produced by granulosa cells from small and medium sized follicles,
      respectively. Although FSH and LH did not change progesterone levels in cultured
      JC-410 cells, forskolin and cholera toxin induced a 2.6- and 2.75-fold increase,
      respectively, versus control. The JC-410 cells responded to 0.1, 1 and 5 mM cAMP
      with an increase in progesterone synthesis of 2.5-, 28- and 49-fold versus
      control, respectively, after a 24 h incubation. No detectable levels of estradiol
      17beta were found in JC-410 cells after 48 h in culture. However, addition of
      0.01, 0.1 and 1 microM androstenedione elevated the levels of estradiol-17beta to
      0.028, 0.3 and 1.21 pg/microg protein, respectively. The level of expression of
      3betaHSD, aromatase and P450scc genes in JC-410 cells is of similar magnitude to
      the level of expression in granulosa cells in primary culture. The JC410 cells
      have been maintained in culture for more than one year during which their
      population doubled over 100 times. We conclude that JC-410 is a stable cell line
      that lost responsiveness to the gonadotropins during the process of
      immortalization, but retained its steroid biosynthetic capability and the
      expression of key steroidogenic genes. These characteristics may reflect features
      of cells arrested in an early stage of granulosa cell differentiation.

PMID- 9584844
TI  - Intramolecular electron transfer between tryptophan radical and tyrosine in
      oligoproline-bridged model peptides and hen egg-white lysozyme.
AB  - Long range electron transfer (LRET) across protein matrix underlies all one
      electron cellular redox reactions. Elucidation of molecular electron transfer
      pathways and parametrization of their relative efficiency is one of the most
      challenging problems in the studies on LRET in proteins. In this paper results of
      pulse radiolysis investigations on kinetics of LRET accompanying intramolecular
      radical transformation Trp. --> TyrO. in model peptides built of tryptophan and
      tyrosine bridged by an oligoproline fragment are reviewed, along with an
      interpretation of the observed distance dependence of the rate of LRET in terms
      of conformational properties of the peptides, and partitioning of LRET between
      electron transfer pathways through space and through peptide backbone. This
      review on model peptide systems is supplemented with recapitulation of similar
      studies on the same intramolecular transformation in hen egg-white lysozyme,
      which allowed to identify Trp./Tyr redox pairs and associated electron transfer
      pathways involved in LRET in this protein.

PMID- 9584845
TI  - Molten globule as an intermediate on the human prostatic phosphatase folding
      pathway.
AB  - Human prostatic acid phosphatase (hPAP, EC.3.1.3.2), a secretory homodimeric
      protein was denatured in 6 M urea, pH 2.5, and refolded by dilution at pH 7.2
      with recovery of the enzymatic activity and dimeric structure. Circular
      dichroism, intrinsic fluorescence and chromatographic analysis of renaturating
      protein suggested that the kinetic intermediate of the hPAP folding is a monomer
      which displays a molten globule state (R. Kuciel, A. Mazurkiewicz & W.S.
      Ostrowski, 1996, Int. J. Biol. Macromol. 18, 167-175). To confirm these data
      experiments were performed to estimate the interaction of the renaturating
      protein with dyes and amphipathic lipid structures. Increased binding of the
      hydrophobic probe 1-anilinonaphthalene-8-sulfonate and Congo Red to the refolding
      enzyme supported the existence of molten globule state with the relaxed beta
      structure in the renaturating protein. Presence of liposomes, included in the
      renaturation mixture as a model of acid phospholipid, resulted in perturbations
      of the human PAP refolding process. Some folding intermediates were bound to
      phosphatidylserine liposomes or, alternatively, water soluble, inactive
      aggregates were formed.

PMID- 9584846
TI  - Covalent modification and site-directed mutagenesis of an active site tryptophan
      of human prostatic acid phosphatase.
AB  - Because tryptophans are found as part of the phosphate binding sites in a number
      of proteins, human prostatic acid phosphatase (hPAP) was examined for the
      presence and the role of essential tryptophan residues. The pH dependence of the
      intrinsic fluorescence of hPAP resembled the kinetic pH dependence. Chemical
      modification by N-bromosuccinimide (NBS) resulted in an inactivation of the
      enzyme and produced a characteristic reduction of the protein absorbance at 280
      nm. Two tryptophans per subunit were modified, and this was accompanied by an
      apparently complete loss of enzymatic activity. In the presence of the
      competitive inhibitor L-(+)-tartrate, the loss of enzyme activity was
      significantly reduced as compared to the rate of tryptophan modification. After
      labeling the protein with 2,4-dinitrophenylsulfenyl chloride (DNPS-Cl), two
      tryptic peptides containing DNPS-labeled tryptophans were isolated and the
      sequences were identified by amino acid sequence analysis and mass spectroscopy.
      One peptide corresponded to residues 172-176, and included Trp174. The other
      corresponded to the C-terminal sequence, including Trp336. It was concluded that
      Trp174 was at the active site of the human enzyme because it was protected by the
      competitive inhibitor tartrate in the DNPS-Cl modification studies. This is also
      consistent with the location of a homologous residue in the structure of the rat
      enzyme. Using site-directed mutagenesis, Trp174 was replaced by Phe or Leu. Both
      mutants showed altered kinetic properties, including lower Km values with several
      aromatic substrates, and also exhibited reduced stability towards urea
      denaturation.

PMID- 9584847
TI  - Prostatic acid phosphatase: structural aspects of inhibition by L-(+)-tartrate
      ions.
AB  - The crystal structure of the complex between rat-prostatic acid phosphatase (PAP)
      and L-(+)-tartrate (Lindqvist et al., J. Biol. Chem., 1993, 268, 20744-20746)
      contains the model of the ligand with incorrect chirality. We report here the
      correct model and discuss the relation between this model and the model of the
      inhibitory complexes between PAP and oxy-anions.

PMID- 9584848
TI  - The role of lysine-256 in the structure and function of sheep liver recombinant
      serine hydroxymethyltransferase.
AB  - The active site lysine residue, K256, involved in Schiff's base linkage with
      pyridoxal-5'-phosphate (PLP) in sheep liver recombinant serine
      hydroxymethyltransferase (rSHMT) was changed to glutamine or arginine by site
      directed mutagenesis. The purified K256Q and K256R SHMTs had less than 0.1% of
      catalytic activity with serine and H4folate as substrates compared to rSHMT. The
      mutant enzymes also failed to exhibit the characteristic visible absorbance
      spectrum (lambda(max) 425 nm) and did not produce the quinonoid intermediate
      (lambda(max) 495 nm) upon the addition of glycine and H4folate. The mutant
      enzymes were unable to catalyze aldol cleavage of beta-phenylserine and
      transamination of D-alanine. These results suggested that the mutation of the
      lysine had resulted in the inability of the enzyme to bind to the cofactor.
      Therefore, the K256Q SHMT was isolated as a dimer and the K256R SHMT as a mixture
      of dimers and tetramers which were converted to dimers slowly. On the other hand,
      rSHMT was stable as a tetramer for several months, further confirming the role of
      PLP in maintenance of oligomeric structure. The mutant enzymes also failed to
      exhibit the increased thermal stability upon the addition of serine, normally
      observed with rSHMT. The enhanced thermal stability has been attributed to a
      change in conformation of the enzyme from open to closed form leading to reaction
      specificity. The mutant enzymes were unable to undergo this conformational change
      probably because of the absence of bound cofactor.

PMID- 9584849
TI  - Primary structure of porcine spleen ribonuclease: sequence homology.
AB  - The primary structure of porcine spleen RNase (RNase Psp1) was investigated as a
      mean of assessing the structure-function relationship of base non-specific
      ribonucleases of animal origin. N-terminal analysis of RNase Psp1 yielded three N
      terminal sequences. These peptides were separated by gel-filtration on Superdex
      75HR, after reduction and S-carboxymethylation of RNase Psp1. Determination of
      the amino-acid sequence of these peptides indicated that the RNase Psp1
      preparation consisted of three peptides having 20 (RCM RNase Psp1 pep1), 15 (RCM
      RNase Psp1 pep2), and 164 (RCM RNase Psp1 pro) amino-acid residues, respectively.
      It possessed two unique segments containing most of the active site amino-acid
      residues of the RNases of the RNase T2 family. The alignment of these three
      peptides in RNase Psp1 was determined by comparison with the other enzymes in the
      RNase T2 family. The overall results showed that RCM RNase Psp1 pep1 and RCM
      RNase Psp1 pep2 are derived from the N-terminal and C-terminal regions of RNase
      Psp1, respectively, probably by processing by some protease. The molecular mass
      of the protein moiety of RNase Psp1 was 23235 Da.

PMID- 9584850
TI  - Female hormones act as natural antioxidants--a survey of our research.
AB  - The increase in the lipid peroxide level in the serum and liver of female mice
      after bilateral ovariectomy evidenced antioxidant activities of female hormones.
      This increase was abolished upon administration of female hormones. Similar
      increase in the level of lipid peroxide was observed in the serum of women who
      had undergone bilateral ovariectomy. Injection of 2-hydroxyestradiol suppressed
      the increase in the lipid peroxide level in the liver of rats receiving whole
      body gamma-ray irradiation. Considering that the mechanism of coronary
      atherosclerosis is ascribed at least in part to the increased level of lipid
      peroxides, estrogen therapy could be applied to women who had undergone bilateral
      ovariectomy prior to menopause or to normal women after menopause. 2
      Hydroxyestradiol might be applied also to men.

PMID- 9584851
TI  - Tumor-specific pyruvate kinase isoenzyme M2 involved in biochemical strategy of
      energy generation in neoplastic cells.
AB  - The differences in properties of pyruvate kinase (EC 2.1.7.40) from normal
      tissues and animal or human tumors are described and their significance for
      various metabolic abnormalities is reviewed. The tumor variant gamma3 from M2
      isoenzyme of pyruvate kinase sensitive to L-cysteine inhibition, when over
      expressed, can be used as a marker of tumorigenic transformation. It seems that
      this variant represents a tumor-specific oncoprotein, involved in a novel
      metabolic strategy of energy generation during increased cell proliferation.

PMID- 9584852
TI  - Selective cobalamin malabsorption and the cobalamin-intrinsic factor receptor.
AB  - The disease is characterised by cobalamin (Cbl) deficiency in children 0-5 years
      old, causing failure to thrive, infections, megaloblastic anaemia, neuropathy,
      and mild general malabsorption; slight proteinuria is common. Cbl injections
      produce remission, but Cbl malabsorption and proteinuria persist. About 250 cases
      have been reported. Dogs also have it. The heredity is autosomal and recessive.
      The physiological and pathological absorption mechanisms are described: Cbl
      liberated from food by digestion is first bound to haptocorrin, but in the
      intestine it is transferred to intrinsic factor. In the ileum the complex
      attaches to a receptor on the enterocytes; this requires neutral pH and Ca2+. The
      receptor is a membrane-bound glycoprotein consisting of multiple subunits. The
      receptor-ligand complex is endocytosed and degraded in lysosomes, and the vitamin
      is transferred to transcobalamin which carries it to tissues. The same receptor
      is strongly expressed in the kidneys, but urine also contains its activity which
      can be assayed for diagnosis. The basic lesion is an error in the ileal receptor.
      In the affected dogs the synthesised receptor is retained intracellularly. Urine
      and ileal biopsies from human cases contained little receptor but it had
      conserved affinity for the ligand. Recently examined Arab patients did not
      excrete reduced amounts of the receptor. Apparently, the disease has subsets,
      such as different structural errors in the receptor and possibly faulty transport
      inside the enterocyte. The cause of the proteinuria is unknown but kidney damage
      due to severe Cbl deficiency and an error in a multiligand renal receptor are
      among the possibilities.

PMID- 9584853
TI  - Synergistic effect of 5-fluorodeoxyuridine and quinazoline antifolates on murine
      leukemia self-cultured in vitro.
AB  - The effect of thymidylate synthase inhibitors, fluorodeoxyuridine (FdUrd) and its
      two sulphonamide derivatives was examined in the culture of murine leukemia cells
      -- 5178Y (parental subline) and its fluorodeoxyuridine resistant subline 5178Y/F.
      A synergistic effect of the antimetabolites on cell survival was observed on
      exposure of the culture of either line to a slightly inhibitory concentration of
      FdUrd (1 nM) in combination with 2-desamino-2-methyl-10-propargyl-5,8-dideaza
      pteroylsulphogluta mate or 2-desamino-2-methyl-10-propargyl-5,8-dideaza
      pteroylsulphoglyci ne. This effect was accompanied by a marked reduction, in both
      cell lines of intracellular concentration of 5,10-methylenetetrahydro-pteroyl
      polyglutamate, although its concentration in the resistant subline was 3 times as
      high as in the parental line. The inhibitory effect of combined drugs on the
      cellular pool of folates in 5178Y line depended also on the sequence of drug
      addition, whereas in the FdUrd resistant line this sequence was without any
      effect. The results obtained strongly suggest that under certain conditions
      inhibition of thymidylate synthesis by antifolates is intensified by a prior use
      of FdUrd.

PMID- 9584854
TI  - The effects of combined antifolates on inhibition of growth of murine leukemia
      cells cultured in vitro.
AB  - The synergistic effect of trimetrexate (TMTX) and sulphonamide derivatives of
      quinazoline on the cultured 5178Y murine leukemia cells was examined. On exposure
      to the slightly inhibitory concentrations of TMTX (0.1 nM) in combination with 2
      desamino-2-methyl-10-propargyl-5,8-dideaza-pteroyl-sulphoglyc ine (DMPDDSF) (0.02
      microM) a synergistic inhibitory effect of the antifolates on cell growth was
      observed. These two drugs in the same combination caused also synergistic
      inhibition of de novo synthesis of thymidylate in intact cells as measured by
      tritium release from [5-(3)H]deoxyuridylate. This was accompanied by a marked
      reduction in intracellular concentration of 5,10-methylenetetrahydro-pteroyl
      polyglutamate (5,10CH2H4PteGlu(n)) (0.2 microM) and dihydropteroyl-polyglutamate
      (0.12 microM). In these conditions de novo biosynthesis of purine was decreased
      by 50%. These observations show that growth inhibition by combined antifolates is
      mediated by intracellular depletion of the substrate of thymidylate synthase --
      5,10CH2H4PteGlu(n). The results obtained strongly suggest that under certain
      conditions inhibition of thymidylate synthesis by DMPDDSF is intensified by prior
      application of TMTX -- an inhibitor of dihydrofolate reductase.

PMID- 9584855
TI  - The effect of dihydrotestosterone on transcription of prostatic acid phosphatase
      mRNA in human hyperplastic gland.
AB  - The effect of 5alpha-dihydrotestosterone (DHT) on the level of human prostatic
      acid phosphatase (hPAP) mRNA was studied using tissue slices from various benign
      prostatic hyperplastic glands. The absence of DHT in the incubation medium led to
      a gradual, significant decrease of the hPAP mRNA level. Addition of the hormone
      induced hPAP mRNA in a time- and dose-dependent manner. The maximal 2-4-fold
      induction by 10(-9) M DHT was observed after 3-5 h of incubation, and then the
      hPAP mRNA level was 6-20-fold higher than that in a parallel sample incubated
      without DHT. The results suggest that DHT is necessary to sustain the expression
      of hPAP in hyperplastic prostates.

PMID- 9584856
TI  - 2-Methyl-thiazolidine-2,4-dicarboxylic acid protects against paracetamol induced
      toxicity in human liver derived HepG2 cells.
AB  - The effects of 2-methyl-thiazolidine-2,4-dicarboxylic acid (CP) on paracetamol
      induced toxicity were investigated and evaluated in a human liver derived HepG2
      cell line. Incubation of the cells with CP (2 mM and 10 mM) drastically
      attenuated the GSH and cysteine depletion caused by toxic concentrations of
      paracetamol (1 mM and 5 mM). When CP (10 mM) was introduced alone into the
      medium, the level of malondialdehyde and the reactive oxygen species were
      maintained at the control levels with a simultaneous increase of non-protein
      sulfhydryl in the cells. Thus, the results of our work prove that CP is a non
      toxic precursor of cysteine and GSH, and successfully prevents paracetamol
      toxicity in HepG2 cells.

PMID- 9584857
TI  - The effect of experimental neoplastic disease on malondialdehyde level and
      glutathione status in erythrocytes of rats.
AB  - The level of lipid peroxidation products and the content of glutathione in
      erythrocytes of rats with Morris 5123 hepatoma at different stages of tumor
      development were examined. The content of endogenous malondialdehyde (MDA) was
      increased throughout all periods of tumor development as compared to the results
      for healthy rats. From the extent of MDA generation under oxidative stress we
      concluded that erythrocytes of Morris 5123 hepatoma bearing rats were more
      susceptible to autoxidation than those from control rats. The content of reduced
      glutathione (GSH) and oxidized glutathione (GSSG) was increased at the early
      stage of tumor growth. At the advanced stage of the disease both the content of
      GSH and the GSH/GSSG ratio were decreased while the content of GSSG remained at
      the elevated level.

PMID- 9584858
TI  - The activity of 3-mercaptopyruvate sulfurtransferase in erythrocytes from
      patients with polycythemia vera.

PMID- 9584859
TI  - Inhibition of mammalian topoisomerase I by 1-nitro-9-aminoacridines. Dependence
      on thiol activation.
AB  - The cytotoxic activity, susceptibility to thiol activation and ability of eight 1
      nitroacridine derivatives to stabilize the topoisomerase I-DNA cleavable complex,
      were compared. Among the acridines tested three compounds exhibited high ability
      to stabilize the cleavable complex. This ability was correlated with
      susceptibility to thiol activation as well as with cytotoxic activity. Our
      results suggest that 1-nitroacridine-DNA adducts interfering with topoisomerase I
      action may contribute to the lethal effects of some 1-nitroacridine derivatives.

PMID- 9584860
TI  - Kainate-evoked modulation of gene expression in rat brain.
AB  - Kainate is a glutamate analog that produces neuronal excitation resulting in
      seizures within hours following its intraperitoneal injection into adult rats.
      Then, at 2-3 days after the treatment, neurodegeneration of apoptotic character
      can be observed in limbic system. As a consequence, plastic reorganization and
      glial reactivation phenomena occur. These physiological and pathological
      responses are reflected by specific changes in gene expression, that can be
      dissected according to their spatio-temporal patterns. The early phase of gene
      expression observed in all hippocampal subfields appears to reflect a sudden
      burst of spiking activity. Changes in mRNA levels restricted to dentate gyrus are
      suggestive of a link to neuronal plasticity. The late gene expression response
      implies its correlation either to neuronal cell death or glial reactivation,
      depending on cellular localization of gene products. Thus analysis of the
      temporal and spatial gene expression pattern in the hippocampus after kainate
      treatment may provide clues revealing specific phenomena to which gene expression
      could be attributed.

PMID- 9584861
TI  - New intron-containing human tRNA(Leu) genes.
AB  - Three new human nuclear tRNA(Leu) genes have been isolated and sequenced using
      the PCR technique. Two of them represent genes containing a CAA anticodon and
      both contain introns of 22 nucleotides in length but differing in sequence.
      Intron-containing prolongated anticodon stems can be folded into a secondary
      structure similar to that of yeast pre-tRNA(Leu). The evolutionary conserved
      secondary structure suggests the same role of intron sequences in the human and
      yeast pre-tRNA(Leu) maturation pathway.

PMID- 9584862
TI  - Two plant signalling peptides: systemin and ENOD 40.
AB  - Recently several new evidences have appeared on biological role of native short
      peptides. This is an overview on two of them occurring in plants: systemin and
      ENOD 40.

PMID- 9584863
TI  - On the specific pattern of long chain polyprenols in green needles of Pinus mugo
      Turra.
AB  - In green needles of Pinus mugo the most abundant polyprenols occur as a mixture
      of prenologues in which the dominant alcohol is built of 16 isoprene units. The
      characteristic spectrum of polyprenols (prenol-15, -16 and -17) was the same
      irrespective of the location of plant and of distinct morphological differences
      observed in the various selected forms of this species. The constant pattern of
      the polyprenols spectrum was preserved throughout the 2-year life span of
      needles, although the level of polyprenols was increased 2-3-fold. The polyprenol
      pattern in Pinaceae family differs from species to species, thus it may serve as
      chemotaxonomic criterion within this systematic group.

PMID- 9584864
TI  - Phosphorylation of sucrose synthase from maize seedlings.
AB  - Two isoforms of sucrose synthase (SS1 and SS2) from maize (Zea mays, var. Mona)
      seedlings co-purified with a calcium and phospholipid dependent protein kinase.
      The enzymatic preparation obtained gave a positive reaction with the antibody
      against mammalian protein kinase C. Maize sucrose synthase was phosphorylated by
      the endogenous protein kinase. Also, mammalian protein kinases (protein kinase C
      and protein kinase A) were able to phosphorylate the 86 kDa subunit of sucrose
      synthase. When excised seedlings were fed [32P]orthophosphate, sucrose synthase
      was also phosphorylated. Microsequencing of in vivo labelled enzyme has shown
      phosphorylation of Ser-15 in SS2. The present work provides evidence that maize
      sucrose synthase is the physiological substrate of the endogenous calcium and
      phospholipid dependent protein kinase(s).

PMID- 9584865
TI  - Characterization of two lipopolysaccharide types isolated from Rhizobium galegae.
AB  - Lipopolysaccharides (LPS) of Rhizobium galegae, a symbiotically nitrogen-fixing
      species of root-nodule bacteria, were isolated by the phenol-water method from
      strain HAMBI 1461, the LPS of which resembled enterobacterial smooth type LPS,
      and from strains HAMBI 1174 and HAMBI 1208, the LPSs of which resembled rough
      type LPS. The results of PAGE analysis of LPSs, Bio-Gel P2 gel filtration of
      polysaccharide fractions and the presence of deoxysugars and 4-O-methyl
      deoxysugar both in the rough and smooth LPSs suggested that rough LPS contained a
      short O-antigenic polysaccharide for which we propose the name short O-chain LPS.
      Accordingly, the smooth LPS is called long O-chain LPS. Despite of the
      differences in the structure of LPS of R. galegae, all strains were equally
      effective in nodulating their hosts. The short O-chain LPS of R. galegae showed
      many features similar to those of phylogenetically related agrobacteria.

PMID- 9584866
TI  - An enigma: the role of viral RNA aminoacylation.
AB  - The first demonstration on the aminoacylation capacity of the RNA genome of a
      plant virus appeared more than 25 years ago. Shortly thereafter, aminoacylation
      of the RNA genome of a number of other plant viruses was observed. This led to
      considerable work on the tRNA-like region of these viral RNAs, and to the first
      demonstration of the presence of pseudoknots in their folding pattern. In spite
      of the vast amount of efforts put into trying to understand the reason for the
      aminoacylation capacity of certain viral RNA genomes, as yet no clear general
      conclusion emerges. It rather looks as though the reason for aminoacylation may
      be different for different viruses, and that aminoacylation may operate at
      different levels in the virus life cycle. Given that certain RNA viruses possess
      structures which resemble that of tRNAs at their 5'- or 3'-termini, it is most
      likely that convergent evolution may have dominated the appearance of such
      structures in the virus world.

PMID- 9584867
TI  - Applications of peptide synthetases in the synthesis of peptide analogues.
AB  - Enzymatically formed peptides show positional variations as well as highly
      conserved amino acids. In the cases of gramicidin S, tyrocidine, linear
      gramicidins, enniatins, echinocandins and viridogrisein in vivo and in vitro
      studies indicate substrate selection at the level of amino acid activation as a
      major control step. Evidence for proof-reading steps beyond activation has been
      obtained in penicillin and cyclosporin biosynthesis. Activated substrate
      analogues may promote the formation of side products such as dipeptides and
      cyclodipeptides. Modifications of intermediates, such as N-methylation, influence
      the rates of peptide synthesis. These control steps pose limitations for the
      application of such enzyme systems in the production of peptide libraries. They
      may originate from a target oriented evolution of these synthetases.

PMID- 9584868
TI  - A novel restriction endonuclease UnbI, a neoschizomer of Sau96I from an
      unidentified psychrofilic bacterium from Antarctica is inhibited by phosphate
      ions.
AB  - A novel type II restriction endonuclease UnbI was isolated from an unidentified
      psychrofilic bacterial strain from Antarctica. UnbI recognizes and cleaves the
      sequence 5'-GGNCC-3', producing 5 nucleotide long sticky ends. In this respect it
      differs from its neoschizomer Sau96I and all other restriction enzymes
      recognizing this sequence. UnbI has a relatively low temperature optimum of 15
      degrees C to 20 degrees C and its activity is completely inhibited by inorganic
      phosphate.

PMID- 9584870
TI  - The pathophysiology of migraine: a review based on the literature and on personal
      contributions.

PMID- 9584869
TI  - Continuous assay for acid phosphatase using 1-naphthyl phosphate as a substrate.
AB  - The described continuous acid phosphatase assay is based on kinetics of the
      release of 1-naphthol in the course of the enzyme-catalyzed hydrolysis of 1
      naphthyl phosphate, measured at 320 nm in aqueous solution and at 322 nm in
      sodium-bis(2-ethylhexyl)sulfosuccinate isooctane-water reverse micelles in a
      broad pH range (1.0-8.2). The method allows precise determination of the initial
      rate of the reaction and therefore may be used in the steady-state and pre-steady
      state studies on the phosphatase-catalyzed reaction. The kinetic parameters (Km
      and kcat) for human prostatic acid phosphatase in aqueous solution and in reverse
      micelles, at pH 3.8, 4.5 and 5.7, by the proposed 1-naphthyl phosphate assay have
      been determined.

PMID- 9584871
TI  - Cognitive correlates of leukoaraiosis in the early stages of Alzheimer's disease.
AB  - To reveal cognitive correlates of leukoaraiosis (LA) in the early stages of
      Alzheimer's disease (AD) and to exclude confounding effects of aging, brain
      atrophy, education and dementive illness on cognition, we carefully selected a
      sample of 37 probable AD patients (NINCDS-ADRDA criteria, Hachinski ischemic
      score < 5) with similar indices of age, educational level, degree of brain
      atrophy and dementia severity (CDR 0.5, CDR 1 and MMSE score no lower than 20),
      and compared the results of neuropsychological testing of patients with and
      without LA. All patients underwent magnetic resonance imaging. LA was detected in
      17 out of 37 cases. There were no significant differences between subjects with
      and without LA (Student's t-test, p>0.05) in tests that evaluate language, verbal
      intelligence and visuospatial functions, while the patients with LA showed poorer
      performance (p<0.05) in the tests evaluating verbal memory,
      attention/concentration and executive functions. The results obtained suggest
      that the patients with LA in the early stages of AD revealed dorsolateral
      prefrontal dysfunction syndrome due to disconnection of cortico-subcortical
      circuits. We found this syndrome to be more prenounced than it has been described
      in the non-demented elderly with LA. It may be that in patients suffering from
      degenerative illness, the brain has fewer compensatory reserves than in cases of
      "normal" aging, and it is more sensitive to ischemic damage caused by cerebral
      amyloid, arteriosclerotic or fibro-hyalinotic angiopathy. This typical
      neuropsychological syndrome is revealed only in the initial stage of AD in
      patients with LA. The follow-up progress of the atrophic-degenerative illness
      leads to overlapping of the specific neuropsychological syndrome by global
      cognitive impairment.

PMID- 9584872
TI  - Carotid artery atherosclerosis and risk factors for stroke in a selected
      population of asymptomatic men.
AB  - The prevalence of carotid atherosclerosis in the general population is variable.
      Also, the relationship between cardiovascular risk factors and carotid
      atherosclerosis has yet to be clearly defined. We carried out a cross-sectional
      study of 441 asymptomatic male subjects to investigate possible relationships
      between extracranial carotid plaques, cardiovascular risk factors and
      asymptomatic coronary obstructive disease. Carotid atheromatous plaques, detected
      by means of B-mode ultrasonography, were present in 31.7% of the study
      population. Prevalence and severity of atherosclerosis were significantly
      correlated with age, total cholesterol and signs of ischemia upon exercise stress
      test. However, hypercholesterolemia seemed to play a significant pathogenic role
      only in the youngest subjects (<55 years old). Our study confirms the high
      prevalence of asymptomatic carotid plaques in the general population, especially
      in elderly subjects. The only reversible risk factor related to carotid
      atherosclerosis is hypercholesterolemia, and this is reversible only at a young
      age.

PMID- 9584873
TI  - Neuroborreliosis in county Baranya, Hungary.
AB  - The incidence and clinical characteristics of Lyme neuroborreliosis (NB) in a
      region of high prevalence of tick-bite in Hungary is described. In the county
      Baranya 66 patients were recorded in a five-year period (1989-93). Fifty-six
      patients (85%) were in "early", and 10 patients (15%) in "late stage" of NB. The
      sex distribution was equal. The incidence of NB was 2.9-100,000/year in this
      region. The incidence of radiculitis/neuritis, meningitis, encephalitis and
      myelitis in the sample was 56.1%, 19.7%, 18.2% and 6%, respectively. The EEG and
      evoked potentials showed both central and peripheral neural involvement, EMG and
      ENG abnormalities were related to the peripheral clinical signs. Non-specific
      white matter lesions could be found by MRI in 5 patients with central
      involvement. Cerebrospinal fluid changes were not obligatory but a better
      indicator of inflammatory process in cases with meningitis and/or encephalitis
      forms (positivity 75%) than in cases with myelitis and radiculitis (positivity
      49%).

PMID- 9584875
TI  - Active music therapy and Parkinson's disease: methods.
AB  - Music therapy (MT) is an unconventional, multisensorial therapy poorly assessed
      in medical care but widely used to different ends in a variety of settings. MT
      has two branches: active and passive. In active MT the utilisation of instruments
      is structured to correspond to all sensory organs so as to obtain suitable motor
      and emotional responses. We conducted a prospective study to evaluate the effects
      of MT in the neurorehabilitation of patients with Parkinson's Disease (PD), a
      common degenerative disorder involving movement and emotional impairment. Sixteen
      PD patients took part in 13 weekly sessions of MT each lasting 2 hours. At the
      beginning and at the end of the session, every 2 weeks, the patients were
      evaluated by a neurologist, who assessed PD severity with UPDRS, emotional
      functions with Happiness Measures (HM) and quality of life using the Parkinson's
      Disease Quality of Life Questionnaire (PDQL). After every session a significant
      improvement in motor function, particularly in relation to hypokinesia, was
      observed both in the overall and in the pre-post session evaluations. HM, UPDRS
      ADL and PDQL changes confirmed an improving effect of MT on emotional functions,
      activities of daily living and quality of life. In conclusion, active MT,
      operating at a multisensorial level, stimulates motor, affective and behavioural
      functions. Finally, we propose active MT as new method to include in PD
      rehabilitation programmes. This article describes the methods adopted during MT
      sessions with PD patients.

PMID- 9584874
TI  - Clinical efficacy and central mechanisms of cyclandelate in migraine: a double
      blind placebo-controlled study.
AB  - The mechanisms of action of calcium antagonists in the prophylactic treatment of
      migraine remain unclear. The most likely proposed mechanism seems to be via
      influence on the central nervous system, but the central effects of calcium entry
      blockers are insufficiently characterized. The aim of the present study was to
      investigate the central mechanisms behind the efficacy of cyclandelate in a
      double-blind placebo-controlled parallel-designed study using the contingent
      negative variation (CNV), an event-related slow potential for measuring cortical
      excitability and investigating preparation processes. The CNV recordings were
      performed in 25 females suffering from migraine without aura before treatment
      (baseline), after single dose administration of cyclandelate or placebo and after
      8 weeks' treatment with cyclandelate (cyclandelate group, no.=15) or placebo
      (placebo group, no.=10). Cyclandelate reduced significantly the days with
      migraine and duration of migraine compared to placebo. In the cyclandelate group
      a significant reduction of all CNV components was observed and the changes in
      amplitudes compared to baseline were more pronounced after treatment. Placebo
      reduced the late CNV component only after single dose administration. There were
      no changes in the early and total CNV. Cyclandelate did not normalize the
      habituation of the slow negative potential. The results are discussed in terms of
      the influence of cyclandelate on cortical excitability and of the prevention of
      cortical spreading depression via antagonistic effect on calcium channels.

PMID- 9584876
TI  - Cervicogenic headache a critical view on pathogenesis.

PMID- 9584877
TI  - Validation of criteria for cervicogenic headache.

PMID- 9584879
TI  - Greater occipital nerve blockades in cervicogenic headache.

PMID- 9584878
TI  - The clinical profile of cervicogenic headache as it emerges from a study based on
      the early diagnostic criteria (Sjaastad et al., 1990).

PMID- 9584880
TI  - Cervical peridural anaesthesia: an essential aid for the indication of surgical
      treatment of cervicogenic headache triggered by degenerative diseases of the
      cervical spine.

PMID- 9584881
TI  - Radiofrequency cervical zygapophyseal joint neurotomy for cervicogenic headache:
      a short term follow-up study.

PMID- 9584882
TI  - Treatment of cervicogenic headaches: radiofrequency neurotomy to the
      sinuvertebral nerves to the upper cervical disc and to the outer layer of the C3
      nerve root or C4 nerve root respectively.

PMID- 9584883
TI  - Epidural steroid-based technique for cervicogenic headache diagnosis.

PMID- 9584884
TI  - Brain stem reflexes in cervicogenic headaches.

PMID- 9584885
TI  - Demographic and socioeconomic determinants of variation in food and nutrient
      intake in an Andean community.
AB  - Understanding the sources of variation in a community's diet is vital for
      development work, as well as being a source of anthropological and cultural
      insights. Previous surveys in the South American Andes suggest that nutrient
      deficiencies may be widespread; however, such interpretations have remained
      tentative since variance in Andean populations' diet has not been thoroughly
      examined. In this paper we consider the variation in diet due to variation in
      age, sex, and socioeconomic status and variation attributed to inter- and
      intraindividual variation in the diet. One to six days of dietary data (mean =
      3.1) were collected via 24 h recalls from 221 residents of a small, rural
      community in highland Ecuador. The contribution of various food groups to the
      diet varied with land holdings and age but not sex. For example, animal-derived
      foods contribute more and tubers contribute less to the diet of the households
      with > or = 5 Ha, and sweets contribute more to the diet of children. The
      interindividual variation in energy and nutrient intake was low and the
      intraindividual variation high relative to developed countries. The consequence
      are twofold. First, because interindividual variability is low, group mean intake
      can be estimated relatively easily, facilitating group comparisons. Second,
      because intraindividual variation is high, individual nutrient intake cannot be
      easily estimated, which will decrease the ability to detect associations between
      nutrient intake and health measures. This knowledge of the sources of dietary
      variation can lead to better study and survey designs in the rural Andes and
      elsewhere in the developing world.

PMID- 9584886
TI  - Risk factors for low birth weight: results from a case-control study in southern
      Spain.
AB  - The main objective of this study is to examine the effect of several variables,
      including altitude of maternal residence, on delivering a low birth weight (LBW)
      newborn. A case-control study was done. Two hundred forty cases (single newborn
      weighing less than 2,500 g) and 374 controls (single newborn weighing more than
      2,499 g) were included. Information was gathered from the clinical chart of
      delivering women, through a personal interview and the Spanish Census Bureau (for
      altitude). Predictors of LBW were assessed through stepwise logistic regression
      analysis. Several well-known LBW risk factors were identified: hypertension,
      weight gain during pregnancy, body size (mainly maternal prepregnancy weight),
      low social class, primiparity, and several conditions (spontaneous delivery,
      abruptio placentae). Altitude was an independent predictor of LBW at term (more
      than 37 weeks of gestational age) but not for preterm LBW. Nevertheless, a
      relationship between altitude and birth weight was not found in controls,
      although a moderate decreasing gradient with altitude was observed. The
      limitations of these findings are discussed.

PMID- 9584887
TI  - Investigating the weaning process in past populations.
AB  - The 19th century St. Thomas'Anglican churchyard in Belleville, Ontario, Canada is
      associated with a large and well-preserved infant skeletal collection (n = 149)
      and good-quality parish records that document interments in the graveyard (1821
      1874). By using a combination of historical demographic and stable nitrogen
      isotope analyses on the parish records and skeletal remains, respectively, a
      general pattern of extended nursing for about 14 months, introduction of foods
      other than breast milk by around 5 months of age, and variation in breast-feeding
      and weaning behaviours were detected for St. Thomas' infants. The results
      demonstrate that it is possible to go beyond the concept of weaning age to
      explore the weaning process in past populations when appropriate and large
      samples of documentary and skeletal data are available.

PMID- 9584888
TI  - Heterochronic processes in human evolution: an ontogenetic analysis of the
      hominid pelvis.
AB  - Changes in pelvic shape in human ontogeny and hominid phylogeny suggest that the
      heterochronic processes involved differ greatly from the neotenic process
      traditionally described in the evolution of the skull. The morphology of 150
      juvenile and adult pelves of African apes, 60 juvenile and adult pelves of modern
      humans, two adult pelves and a juvenile hip bone of australopithecines (Sts 14,
      AL 288, MLD 7) was studied. Multivariate results, ontogenetic allometries, and
      growth curves confirm that the pelvic growth pattern in humans differs markedly
      from those of the African apes. The results permit the following conclusions.
      First, the appearance of a new feature (acetabulo-cristal buttress and cristal
      tubercle) at the time of human birth allows the addition of traits, such as the
      attainment of a proportionally narrower pelvis, with more sagittally positioned
      iliac blades. Pelvic proportions and orientation change progressively in early
      childhood as bipedalism is practiced. Other changes in pelvic proportions occur
      later with the adolescent growth spurt. Second, comparison of juvenile and adult
      australopithecines to modern humans indicates that 1) some pelvic traits of adult
      Australopithecus resemble those of neonate Homo; 2) the pelvic growth of
      Australopithecus was probably closer to that of apes, than to that of humans; and
      3) prolonged growth in length of hindlimb and pelvis after sexual maturity seems
      to be a unique feature of Homo. The position of the acetabulo-cristal buttress
      and of the cristal tubercle on the ilium are similar in adult Australopithecus
      and neonate Homo suggesting that this feature may have been displaced later
      during hominid evolution. Progressive displacement of the acetabulo-cristal
      buttress on the ilium occurs both during hominid evolution (from Australopithecus
      to Homo sapiens) and human growth (from neonate to adult). This suggests
      peramorphic evolution of the pelvic morphology of hominids combining three
      processes of recapitulation (pre-displacement, acceleration and time
      hypermorphosis). The results lend credence to the hypothesis that no single
      heterochronic process accounts for all human evolutionary change; rather this
      reflects a combination of relative changes in growth rhythm and duration,
      including other perturbations, such as the appearance of new morphological
      features.

PMID- 9584889
TI  - Underestimating intraspecific variation: the problem with excluding Sts 19 from
      Australopithecus africanus.
AB  - Two analyses conclude that Sts 19 cannot be accommodated within the
      Australopithecus africanus hypodigm (Kimbel and Rak [1993] In Kimbel and Martin
      [eds.]: Species, Species Concepts, and Primate Evolution. New York: Plenum, pp.
      461-484; Sarmiento [1993] Am. J. Phys. Anthropol. [Suppl.] 16:173). Both studies
      exclude Sts 19 because it possesses synapomorphies with Homo. Furthermore,
      according to Kimbel and Rak (1993), including Sts 19 in A. africanus results in
      an unacceptably high degree of polymorphism. This study aims to refute the null
      hypothesis that Sts 19 belongs to A. africanus. Twelve basicranial characters, as
      defined and implemented in Kimbel and Rak's study, were scored for casts of seven
      A. africanus and seven Homo habilis basicranial specimens. These characters were
      also examined on specimens from a large (N = 87) sample of African pongids.
      Contrary to Kimbel and Rak's (1993) findings, the null hypothesis is not refuted.
      The degree of polymorphism among A. africanus with Sts 19 included is less than
      that seen in Pan troglodytes. In addition, Sts 19 shares only one apomorphy with
      Homo. However, when treated metrically, Sts 19's morphology for this character is
      not significantly divergent from other A. africanus specimens.

PMID- 9584890
TI  - Capture techniques and morphological measurements of the mona monkey
      (Cercopithecus mona) on the island of Grenada, West Indies.
AB  - Morphological measurements were collected from 12 wild and 12 captive mona
      monkeys (Cercopithecus mona) on the Caribbean island of Grenada. Mona monkeys
      were introduced to Grenada from Africa approximately 200 to 300 years ago during
      the slave trade era. Wild monkeys were captured using either 1) a baited treadle
      door trap and anesthetic-filled darts fired from a blowpipe, or 2) rifle-fired
      anesthetic-filled darts. All wild monkeys were released back into the forest
      after capture and were seen with their original groups within 24 hours of
      release. Captive monkeys were anesthetized using blowpipe-fired darts. A
      Ketaset/Rompun mixture was the most effective anesthetic for wild monkeys while
      Ketaset alone was suitable for captive monkeys. Responses to and recovery times
      from both drugs varied among individuals. Data on eight linear body measurements,
      canine length, testicle size, and weight were collected from all monkeys. Adult
      monkeys were significantly sexually dimorphic across all measurements. Mean adult
      male weight (mean = 4.7, SD = 0.9, n = 13) was almost twice that of adult females
      (mean = 2.8, SD = 0.8, n = 7). No significant differences in weight or
      measurements were found between adult wild and captive males. Preliminary
      comparisons with morphometrics for African C. mona from the literature showed the
      upper limit of Grenada mona body length and weight to be smaller than that of
      African monas for both sexes. These differences may be due to genetic divergence,
      ecological adaptation, inter-African geographic variation, and/or small sample
      sizes.

PMID- 9584891
TI  - Comparative locomotion and habitat use of six monkeys in the Tai Forest, Ivory
      Coast.
AB  - The relationships between locomotion, body size, and habitat use in six sympatric
      Old World monkeys are examined to test whether the associations found are
      consistent with those demonstrated in previous studies (Fleagle and Mittermeier
      [1980] Am. J. Phys. Anthropol. 52:301-314; Gebo and Chapman [1995] Am. J. Phys.
      Anthropol. 97:49-76). Colobus polykomos, C. badius, C. verus, Cercopithecus
      diana, C. campbelli, and Cercocebus atys were studied for 14 months in the Ivory
      Coast's Tai Forest. Analyses reveal that (1) larger monkeys tend to frequent
      those strata containing the greatest densities of large supports while smaller
      monkeys are more diverse in their canopy use; (2) high frequencies of leaping are
      not necessarily confined to the understory, and understory specialists are not
      necessarily frequent leapers; (3) body size does not consistently predict leaping
      or climbing frequencies; (4) in general, climbing is more frequent during
      foraging and leaping is more common during travel; (5) larger supports are used
      during travel while smaller supports are used during foraging; and (6) larger
      monkeys do not always use larger supports than do smaller monkeys. Some of the
      factors contributing to the manner that locomotion, body size, and habitat use
      are related in cercopithecid monkeys are discussed.

PMID- 9584892
TI  - Age, dominance rank, natal status, and tenure among male macaques.
AB  - Age and rank are often related among males in multi-male groups of macaques.
      However, recent studies have not consistently reported that age and rank are
      correlated. This paper reviews studies providing data on at least age and rank
      for each individual in the sample to investigate how the demographic composition
      of data samples can affect whether statistical analysis finds significant
      correlations between age and rank. I reanalyzed data on the age composition,
      natal status, and length of tenure of the males comprising the samples.
      Significant nonlinear age-rank relations existed in four of seven studies
      reviewed. Samples lost statistical significance after removing younger
      individuals, but at different lower age limits. Samples showing no significant
      age-rank correlation consisted mostly of adults or natal males. The length of
      tenure in a troop and natal status showed strong correlations with residuals of
      the nonlinear age-rank regressions, implying that these factors tend to weaken
      age-rank correlations, but tenure may have little effect independent of age among
      males staying in troops longer than about 1 year. The data suggest that the
      demographic composition of study samples, especially age, may still explain some
      differences in conclusions among studies on rank and reproductive success focused
      on "adult" samples. Relatively younger or older males may have contributed to
      significant correlations between rank and measures of mating success, as they do
      for age and rank. Primatologists may need to apply nonlinear statistical
      techniques to samples composed of wide age ranges without subdivision to
      investigate the causes of both the cross-age and within-age variation in
      dominance rank or reproductive success.

PMID- 9584893
TI  - Taxonomic and functional implications of mandibular scaling in early hominins.
AB  - Body mass estimates for fossil hominin taxa can be obtained from suitable
      postcranial and cranial variables. However, the nature of the taphonomic
      processes that winnow the mammalian fossil record are such that these data are
      usually only available for the minority of the specimens that comprise the
      hypodigm of a species. This study has investigated the link between species mean
      body mass and the height and width of the mandibular corpus in a core sample of
      23 species of extant simians. The slopes of the least-squares regressions for the
      whole sample and for the hominoid subset are similar. However, the intercepts
      differ so that for a given body mass, a hominoid will generally have a smaller
      mandible than a generalized simian. The same mandibular measurements were taken
      on 75 early hominin mandibles assigned to eight species groups. When mandibular
      corpus height- and width-derived estimates of body mass for the fossil taxa were
      compared with available postcranial and cranial-derived body mass estimates, the
      eight early hominin species sort into four groups. The first, which includes A.
      afarensis and A. africanus, has mandibles which follow a "generalized simian"
      scaling relationship. The second group, which comprises the two "robust"
      australopithecine species, P. boisei and P. robustus, has mandibles which scale
      with body mass as if they are "super-simians," for they have substantially larger
      mandibles than a simian with the same body mass. The two "early Homo" species, H.
      habilis sensu stricto and H. rudolfensis, make up the third group. It has
      mandibular scaling relationships that are intermediate between that of the
      comparative simian sample and that of the hominoid subsample. The last of the
      four groups comprises H. ergaster and H. erectus; their mandibles scale with body
      mass as if they were hominoids, so that of the four groups they have the smallest
      mandibles per unit body mass. These results are related to comparable information
      about relative tooth size. Their relevance for attempts to interpret the dietary
      adaptations of early hominins are explored.

PMID- 9584895
TI  - Brief communication: stature estimation in extinct Aonikenk and the myth of
      Patagonian gigantism.
AB  - The Aonikenk were a hunter-gatherer group that inhabited the southern extreme of
      Patagonia at European Contact and became extinct at the end of the 19th century.
      The myth of Patagonian gigantism developed around these aborigines from early
      Spanish explorer accounts. In this study, the postcranial remains belonging to
      the Aonikenk (Patagonia) and the Selk'nam (Tierra del Fuego) preserved at the
      Instituto de la Patagonia (UMAG, Chile) have been measured, using standard
      metrics. Different stature estimations for these groups have been generated, by
      using the different regression formulae available. Aonikenk male stature appears
      to be between 174 and 178 cm on average, whereas the Selk'nam are considerably
      shorter. In addition, stature estimations from Spanish populations dating to the
      contact period have been compiled for comparison. While it can be concluded that
      the Aonikenk probably presented the highest stature values of all Meso- and South
      American populations, it is suggested that the perception of their gigantism
      could be partially attributed to the real difference in stature (probably more
      than 10 cm) between these aborigines and contemporaneous Europeans.

PMID- 9584894
TI  - Technical note: improved DNA extraction from ancient bones using silica-based
      spin columns.
AB  - We describe a simple method for extracting polymerase chain reaction-amplifiable
      DNA from ancient bones without the use of organic solvents. Bone powders are
      digested with proteinase K, and the DNA is purified directly using silica-based
      spin columns (QIAquick3, QIAGEN). The efficiency of this protocol is demonstrated
      using human bone samples ranging in age from 15 to 5,000 years old.

PMID- 9584896
TI  - Apoptotic cell death and the proliferative capacity of human breast cancers.
AB  - The proliferative capacity (%S-phase fraction), DNA ploidy, apoptosis frequency
      (DNA fragmentation) and steroid hormone receptor status (estrogen receptor, ER;
      progesterone receptor, PR) of 110 samples of human breast tissues with ductal
      invasive carcinoma were measured using biochemical and cytofluorimetric
      procedures. The DNA fragmentation had a left-skewed frequency distribution and an
      overall median value of 1.64%, whilst the median %S-phase fraction was 8%. The
      median %DNA fragmentation and %S-phase fraction were 1.96% and 16% in
      hyperdiploid tumours (n = 29; DNA index >1.1) higher than in hypodiploid tumors
      (n = 10; DNA index <0.96), 0.38% and 7.5%. DNA diploid tumours (n = 71) had
      median %DNA fragmentation and %S-phase values of 1.68% and 6%, consistently lower
      than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid
      tumours was about one half (median: 5.9 fmol/mg) the median values in
      hyperdiploid (10.6 fmol/mg) and diploid tumours (14.6 fmol/mg). This may
      correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least
      when measured by biochemical methods which only detect cells in the late phases
      of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than
      in hypo and/or diploid tumours. The %S-phase/%fragmented DNA ratio for the
      hypodiploid tumours was 19.7, significantly higher than the ratios for
      hyperdiploid (8.2) and diploid tumours (3.6). These findings indicated that there
      is an imbalance between proliferative capacity and cell death or growth arrest in
      human breast tumours. This imbalance may well be linked to a loss of steroid
      hormone control.

PMID- 9584897
TI  - DNA-cytometry of progressive and regressive cervical intraepithelial neoplasia.
AB  - A retrospective analysis was performed on archival cervical smears from a group
      of 56 women with cervical intraepithelial neoplasia (CIN), who had received
      follow-up by cytology only. Automated image cytometry of Feulgen-stained DNA was
      used to determine the differences between progressive and regressive lesions. The
      first group of 30 smears was from women who had developed cancer after initial
      smears with dysplastic changes (progressive group). The second group of 26 smears
      with dysplastic changes had shown regression to normal (regressive group). The
      goal of the study was to determine if differences in cytometric features existed
      between the progressive and regressive groups. CIN categories I, II and III were
      represented in both groups, and measurements were pooled across diagnostic
      categories. Images of up to 700 intermediate cells were obtained from each slide,
      and cells were scanned exhaustively for the detection of diagnostic cells.
      Discriminant function analysis was performed for both intermediate and diagnostic
      cells. The most significant differences between the groups were found for
      diagnostic cells, with a cell classification accuracy of 82%. Intermediate cells
      could be classified with 60% accuracy. Cytometric features which afforded the
      best discrimination were characteristic of the chromatin organization in
      diagnostic cells (nuclear texture). Slide classification was performed by
      thresholding the number of cells which exhibited progression associated changes
      (PAC) in chromatin configuration, with an accuracy of 93 and 73% for diagnostic
      and intermediate cells, respectively. These results indicate that regardless of
      the extent of nuclear atypia as reflected in the CIN category, features of
      chromatin organization can potentially be used to predict the malignant or
      progressive potential of CIN lesions.

PMID- 9584898
TI  - Automatic quantification of immunohistochemically stained cell nuclei using
      unsupervised image analysis.
AB  - A method for quantification of images of immunohistochemically stained cell
      nuclei by computing area proportions is presented. The image is transformed by a
      principal component transform. The resulting first component image is used to
      segment the objects from the background using dynamic thresholding of the P2/A
      histogram, where P2/A is a global roundness measure. Then the image is
      transformed into principal component hue, defined as the angle around the first
      principal component. This image is used to segment positive and negative objects.
      The method is fully automatic and the principal component approach makes it
      robust with respect to illumination and focus settings. An independent test set
      consisting of images grabbed with different focus and illumination for each field
      of view was used to test the method, and the proposed method showed less
      variation than the intraoperator variation using supervised Maximum Likelihood
      classification.

PMID- 9584899
TI  - Synovial sarcoma. Evaluation of prognosis with emphasis on the study of DNA
      ploidy and proliferation (PCNA and Ki-67) markers.
AB  - Controversy still exists regarding the validity of parameters commonly used in
      the evaluation of prognosis of patients with synovial sarcoma (SS). Forty-nine
      cases of previously untreated primary SS (23 females and 26 males, ranging in age
      from 7 to 81, with 31 tumors located in the lower extremity, 8 at the upper
      extremity and 10 at the trunchus), without regional lymph-node or distant
      metastases were studied. We investigated the relationship between (flow and
      image) DNA cytometry, proliferation activity, clinicopathologic parameters, and
      relapse-free and overall survival of the patients. The prognostic value of
      gender, age, duration of symptoms, location, compartmentalization, size, adequacy
      of surgical margins, residual tumor, adjuvant therapy, histologic subtype, extent
      of necrosis, glandular differentiation, calcification, and extent of
      hemangiopericytic areas, mitotic rate, amount of mast cells, blood vessel
      invasion, histologic (UICC and NCI) grades, DNA ploidy, percentage of cells in S
      and S+G2 phases, PCNA and Ki-67 labeling indices (LI), and TNM (UICC) stage of
      the tumors, were evaluated by univariate and multivariate (Cox hazard model)
      analyses. Short duration of symptoms (<12 months), biphasic SS, scarcity of mast
      cells (<10/10 HPF), high mitotic rate (> or =10/10 HPF), high histologic grade
      (grade 3), high PCNA-LI (> or =20%), high Ki-67-LI (> or =10%), DNA aneuploidy,
      and advanced TNM stage (stage III) were features associated with significantly
      shorter relapse-free and overall 5-year survival rates in the univariate
      analyses. Scarcity of mast cells, high mitotic rate, or high PCNA-LI were
      significant predictors of poor survival, in addition to TNM stage in the
      multivariate analyses. The amount of mast cells was inversely correlated with
      mitotic rate and PCNA-LI. Scarcity of mast cells, high mitotic rate, or high PCNA
      LI are factors associated with poor prognosis, in addition to advanced TNM stage
      in patients with localized SS.

PMID- 9584900
TI  - Dental filling materials. Hazards to patients and to environment? Introduction.

PMID- 9584901
TI  - Toxicological aspects on the release and systemic uptake of mercury from dental
      amalgam.
AB  - This paper summarizes some recent reports on mercury release from amalgam
      fillings and resulting concentrations in biological fluids, development of
      antibiotic resistance, and kidney function. In a series of studies of subjects
      with amalgam fillings, mercury (Hg) levels were followed in saliva, feces, blood,
      plasma, and urine before and until 60 d after removal of all of the fillings. The
      Hg concentrations in saliva remained elevated for at least 1 wk, suggesting that
      dissolved Hg vapor is not the major source of mercury in mixed saliva. An
      absorption phase of Hg was seen in plasma during 24 h after amalgam removal.
      After 60 d the plasma Hg concentration was reduced to 40%, of the baseline level.
      The decrease per amalgam surface was 0.11 nmol/l (range 0.02 0.40). The Hg level
      in feces increased two orders of magnitude two days after amalgam removal. At day
      60, the median Hg concentration was still slightly higher than the median value
      of the amalgam free control group. The resistance patterns of the oral and
      intestinal microflora in these subjects were also studied. In the intestinal
      microflora, the relative amount of intestinal microorganisms resistant to 50
      microM HgCl2 peaked 7 d after removal of the amalgam fillings, with a median
      value per sample of 6.1%, compared to 1.3% in samples collected prior to the Hg
      exposure. However, no statistical differences in the resistance pattern of the
      oral microflora were detected between the control and the experimental groups. A
      number of sensitive kidney function parameters were measured 1 wk before and 1,
      2, and 60 d after amalgam removal. No effects on the various kidney parameters
      studied were recorded. According to the conclusions of independent evaluations
      from different state health agencies, the release of mercury from dental amalgam
      does not present any non-acceptable risk to the general population.

PMID- 9584902
TI  - Substances released from dental resin composites and glass ionomer cements.
AB  - An increasing number of cavities in the primary and permanent dentition is
      restored with tooth-colored materials, especially dental resin composites or
      glass ionomer cements. Several investigations have revealed that various
      components are segregated from different composite filling materials into an
      aqueous environment after polymerization. Most organic substances can be
      extracted from a set resin by organic solvents (methanol, tetrahydrofuran,
      ethanol). Furthermore, in most studies, the co-monomer TEG-DMA has been
      identified as the main compound released from polymerized resin composites into
      aqueous media. However, small quantities of the monomers (Bis-GMA, UDMA) and
      other co-monomers, as well as additives, may also be released into water. Very
      little data have been published about substances released from various types of
      glass ionomer cements (GIC), except the liberation of fluoride. Erosion studies
      have revealed that there is a considerable disintegration of GICs at lower pH
      values. However, the nature of the eroded substances has not yet been clarified.
      Altogether, the data presented in this review indicate that information is
      comparably scarce for resin composites and GICs in comparison to the rich amount
      of knowledge concerning amalgams. Therefore, further studies are necessary to
      determine quality and quantity of substances segregated from resin composites and
      GICs.

PMID- 9584903
TI  - The biocompatibility of non-amalgam dental filling materials.
AB  - Non-amalgam filling materials may release substances which have been shown to be
      toxic in cytotoxicity tests and implantation studies. However, results from
      systemic toxicity tests do not indicate any unacceptable risk to the patient's
      general health, but data for non-amalgam dental filling materials are scarce in
      comparison to amalgam. Although estrogen-like effects of one fissure sealant have
      been claimed, no conclusions can be drawn at present for the patient from these
      in vitro data because of the limitation of the test methods and materials used.
      Some components of composite resins/dentin adhesives and a resin-modified glass
      ionomer cement were mutagenic mainly in in vitro tests. Due to the limitations of
      the test systems and the comparatively high concentrations needed to elicit the
      reactions, no unacceptable risk can yet be derived from those data for the
      patient. However, a no-touch technique is recommended for the dental personnel.
      As with amalgam, local reactions of the pulp are not expected with alternative
      filling materials, if the pulp tissue is not exposed and if bacterial penetration
      is avoided. The latter requirement is still difficult to fulfill, especially for
      composite resin systems and related materials in posterior teeth situations.
      Slight gingival reactions to alternative filling materials and to amalgams are
      mainly attributed to plaque accumulation. From all these data it can be concluded
      that, for the time being, it is not possible to rank dental filling materials in
      respect to their biocompatibility, and it is evident that biocompatibility must
      be considered to the same extent for both amalgams and commonly used or
      recommended alternative filling materials.

PMID- 9584904
TI  - Skin and mucosal reactions associated with dental materials.
AB  - The selection of dental materials for specific treatment purposes is primarily
      based on their physical properties. The composition of materials available
      indicates that there is the potential for adverse biological effects. The amounts
      of substances released are usually too low to cause any overt systemic toxic
      effects. However, many of the chemicals used in dentistry are irritating and may
      cause local damage. Also, in reactions mediated via the amplifying mechanisms of
      the immune system, small amounts may lead to clinical manifestations of allergic
      contact dermatitis and urticaria. A special problem in the diagnosis of adverse
      events occurs when intraoral exposure leads to generalized urticarial reactions.
      Due to a low level of suspicion, extraoral reactions are rarely associated with
      dental treatment modalities. Occupational dermatoses represent a serious problem,
      especially the development of an allergy to constituents of the resin-based
      filling materials and adhesives. The monomers of resin-based materials are
      volatile and penetrate latex and vinyl gloves easily. Allergic contact dermatitis
      related to resin-based materials may be occupationally disabling.

PMID- 9584905
TI  - Environmental aspects of dental filling materials.
AB  - In recent years, the possible environmental impact caused by certain routines in
      dental practice has attracted attention among regulators. As part of point source
      reduction strategies, the discharge of mercury/amalgam-contaminated wastes has
      been regulated in a number of countries, even though it has been documented that
      by adopting appropriate mercury hygiene measures, including installation of
      amalgam-separating devices, the environmental impact of amalgam use in dentistry
      is minimal. There are, so far, no data indicating the environmental impact of
      methacrylate-based dental filling materials. As to the occupational environment,
      recent reports have stated that when normal occupational recommendations for
      proper mercury hygiene routines are followed (e.g., water spray coolant and high
      vacuum suction during removal of amalgam restorations), no occupational health
      risk can be assumed. An increasing number of reports on occupational allergic
      reactions to components of polymer-based dental filling materials call for
      attention to the sensitizing potential of certain ingredients in these products.

PMID- 9584906
TI  - Implications of resource-ratio theory for oral microbial ecology.
AB  - The ability to compete for the limited nutrients available to the microorganisms
      of dental plaque is a strong ecological determinant of the structure of the
      subgingival ecosystem. This paper introduces a new concept from the field of
      ecology, resource-ratio theory, and applies it to the dynamics of microbial
      dental plaque with emphasis on the putative periodontal pathogens. Resource-ratio
      theory is a mechanistic theory of resource competition that utilizes pairs of
      growth-limiting nutrients in a stoichiometric fashion to predict zones of
      competitive dominance, exclusion, and coexistence for organisms competing for
      these resources. Once these resource pairs are identified for plaque organisms,
      resource-ratio theory may provide predictions of changes in the microbial
      community structure of plaque based on directional changes in their resource
      supply ratios.

PMID- 9584907
TI  - Intra-individual variations of salivary microbial levels in young adults.
AB  - The variations of salivary levels of total viable flora, oral streptococci,
      Streptococcus mutans, Lactobacillus and Candida in twenty-three subjects, over a
      6-month period, trying to control many potential sources of variability, were
      investigated. Most subjects showed log count variations of the microbial
      parameters larger than 1. They were 95.6% (total flora), 91.2% (oral
      streptococci), 73.9% (lactobacilli), 60.8% (Strep. mutans) and 30.3% (Candida).
      The intra-individual fluctuations were larger than the fluctuations of the means
      of the counts between samples. This suggests that the shifts in levels of these
      micro-organisms were more frequent intra-individually than at a population level.
      Strep. mutans levels significantly explained Streptococcus-Oral (inverse
      correlation), Lactobacillus and Candida variability. The reported variations were
      due to technical and biological factors and suggest that, in order to assess the
      salivary level of some microbial parameters in an individual, the mean count and
      the range of counts, obtained by more than two samples taken under the same
      conditions, should be considered.

PMID- 9584908
TI  - Effect of semi-annual applications of a chlorhexidine/fluoride varnish mixture on
      approximal caries incidence in schoolchildren. A three-year radiographic study.
AB  - Development and progression of approximal caries is still difficult to prevent
      and control even in societies with declining caries prevalence. In this study, a
      test group of 115 12-yr old children were treated semi-annually with a mixture
      (1:1) of a varnish containing 0.1% F (Fluor Protector) and 1.0% chlorhexidine
      (Cervitec). A reference group of 104 children received fluoride varnish treatment
      (Fluor Protector) semi-annually. Approximal caries was recorded from bitewing
      radiographs at baseline and after 3 yr. At baseline, total decayed and filled
      surfaces (DFS) including enamel caries were 1.79+/-2.36 in the reference group
      and 2.0+/-2.77 in the test group. After 3 yr, the mean approximal caries
      incidence including enamel caries was 3.01+/-3.74 and 3.78+/-4.32, respectively.
      The differences at baseline as well as after 3 yr were not statistically
      significant. The results showed that both groups had a comparatively low
      incidence of approximal caries during the experimental period, and suggest that a
      mixture of fluoride and antibacterial varnish had no additional preventive effect
      on approximal caries incidence compared with fluoride varnish treatments alone.

PMID- 9584909
TI  - Triclosan: cytotoxicity, mode of action, and induction of apoptosis in human
      gingival cells in vitro.
AB  - The in vitro cytotoxicology of triclosan, the active ingredient in some
      mouthrinses and dentifrices used in the prevention and treatment of gingivitis
      and plaque, was studied using the Smulow-Glickman (S-G) human gingival epithelial
      cell line. The 24 h midpoint cytotoxicity value was 0.05-0.06 mM triclosan as
      assessed with the neutral red (NR) assay. Triclosan is used in dentifrices in
      combination with either zinc citrate or sodium fluoride (NaF). The sequence of
      potencies of these test agents, as assessed with the NR assay, was triclosan>zinc
      citrate>>NaF; combinations of triclosan + zinc citrate and triclosan + NaF were
      additive in their toxicities. Damage to the integrity of the plasma membrane, as
      assessed by the leakage of lactic acid dehydrogenase during a 3-h exposure, was
      initially evident with 0.1 mM triclosan. When exposed to triclosan for 3 d, a lag
      in the growth kinetics of the S-G cells was first observed at 0.01 mM triclosan.
      A reduction in attachment of S-G cells to dentin chips, previously exposed to
      triclosan for 1 h, was noted at 0.25 mM triclosan and greater. Triclosan-induced
      cell death was apparently by apoptosis, as noted by fluorescence microscopy and
      DNA agarose gel electrophoresis of extracted oligonucleosomal fragments.

PMID- 9584910
TI  - Effect of triclosan on interleukin-1 beta production in human gingival
      fibroblasts challenged with tumor necrosis factor alpha.
AB  - The effect of the dentifrice ingredient triclosan (2,4,4'-trichloro-2'
      hydroxyldiphenyl ether) on the production of interleukin (IL)-1beta and IL-6 was
      studied in human gingival fibroblasts challenged with tumor necrosis factor alpha
      (TNFalpha) in vitro. When gingival fibroblasts were treated simultaneously with
      triclosan (0.25, 0.5 microg/ml) and TNFalpha (10 ng/ml), the stimulatory effect
      of TNFalpha on IL-1beta production was reduced by the agent. In situ
      hybridisation showed that the TNFalpha-induced expression of IL-1beta mRNA was
      significantly reduced by triclosan. Furthermore, when the cells were treated
      simultaneously with a known protein kinase C (PKC) activator, phorbol 12
      myristate-13-acetate (PMA) and TNFalpha in the presence of triclosan (0.5
      microg/ml), the agent reduced the production of IL-1beta. In contrast to its
      effect on IL-1beta, triclosan did not influence the mRNA expression or the
      production of IL-6 induced by TNFalpha. The finding that triclosan reduces the
      production of the inflammatory mediator IL-1beta in gingival fibroblasts further
      supports the view that triclosan exhibits an anti-inflammatory effect.

PMID- 9584911
TI  - Cholesterol crystals as an etiological factor in non-resolving chronic
      inflammation: an experimental study in guinea pigs.
AB  - The presence of cholesterol crystals has been suggested to be a factor
      interfering with periapical healing after conventional endodontic treatment. This
      investigation addresses the role of cholesterol crystals in impairing healing by
      studying the tissue response to the crystals, which were implanted in animals.
      Pure cholesterol crystals, prepared to a mushy form, were placed in Teflon cages
      that were implanted subcutaneously in guinea pigs. The cage-contents were
      retrieved after 2, 4 and 32 wk of implantation and processed for light and
      electron microscopy. The cages revealed delicate connective tissue that grew in
      through perforations on the cage-wall. The crystals were densely surrounded by
      numerous macrophages and multinucleated giant cells, forming a well-circumscribed
      area of tissue reaction. The cells, however, were unable to eliminate the
      crystals during an observation period of 8 months. The congregation of
      macrophages and giant cells, known to be major sources of apical inflammatory and
      bone resorptive mediators, suggest that accumulation of cholesterol crystals can
      be a factor in the failure of certain apical periodontitis lesions to resolve
      after conventional root-filling therapy.

PMID- 9584912
TI  - Accuracy of irreversible hydrocolloids (alginates) for fixed prosthodontics. A
      comparison between irreversible hydrocolloid, reversible hydrocolloid, and
      addition silicone for use in the syringe-tray technique.
AB  - One reversible, seven irreversible hydrocolloids and two addition silicones were
      examined. The aim was to study their ability to reproduce six differently shaped
      abutments of a full arch stainless steel master model correctly, by measuring: 1)
      the accuracy of irreversible hydrocolloid impressions with different storage
      periods of 15 min, 2 h, 24 h and 95 h, reversible hydrocolloid stored 15 min and
      2 h, and Type III addition silicones stored 24 h when the syringe-tray technique
      was used; and 2) whether mixing technique or tray design had any influence of the
      accuracy of irreversible hydrocolloid impressions. All the tested impression
      materials had difficulties in producing full arch casts, where the six abutments
      were correctly reproduced, because 58% of the heights and 45% of the diameters of
      the occlusal surfaces were shorter than the corresponding distances of the master
      model. Storage time, mixing technique and tray design were of significant
      importance for the irreversible hydrocolloids. Concerning the accuracy at the
      gingival margin, a shorter storage time resulted in improved accuracy, and
      mechanical mixing without a vacuum and a tray designed similar to a perforated
      stock tray gave most accurate impressions.

PMID- 9584913
TI  - Fracture properties of aged and post-processed dental composites.
AB  - The purpose of this study was to determine the flexure strength (sigma f),
      Young's modulus (E), and fracture toughness (KIC) of five dental composites after
      aging in water and air. The composites were, by weight, 75% or 79% glass filler
      and 25% or 21% resin composed of 60% Bis-GMA and 40% TEG-DMA. The filler was
      either strontium glass (75Sr or 79Sr) or a combination, by weight, of 90%
      strontium glass and 10% colloidal silica (75Sr10 or 79Sr10). The specimens, 2 x 4
      x 70 mm bars, were aged in either air or distilled water at 37 degrees C and were
      tested in their respective aging media at a loading rate of 1.22 mm/s. The sigma
      f and E were tested in four-point loading and the KIC in three-point loading. The
      addition of the fillers to the unfilled resin resulted in a statistically
      significant increase in the flexure strength, flexure modulus, and fracture
      toughness. Aging in air had minimal effect on these properties. However, testing
      and aging in water led to a significant decrease in the mechanical properties in
      the first 6 months, but had limited effect from 6 to 12 months.

PMID- 9584914
TI  - Correlation between apoptosis distribution and BMP-2 and BMP-4 expression in
      vestigial tooth primordia in mice.
AB  - The eutherian dental formula consists of three incisors, one canine, four
      premolars and three molars in each dental quadrant. Muroid evolution led to a
      reduction in the number of teeth, with one incisor separated from three molars by
      a long diastema. However, seven vestigial tooth primordia (D1-5, R1-2) have been
      detected in the embryonic diastemal area of the mouse maxilla between embryonic
      days (ED) 12.5 and 13.5. Computer-aided 3D reconstructions were used to analyse
      the temporo-spatial pattern of apoptosis during regression in the two largest and
      most distal vestiges (R1, R2). These structures have been widely considered as
      the primordium of the first upper molar and, accordingly, related molecular data
      have been interpreted exclusively in terms of progressive molar development. The
      spatial distribution of epithelial apoptosis, which affected the R1 and R2
      rudiments in two consecutive waves on ED 12.5 and 13.5, respectively, was
      compared with our earlier data on expression of genes encoding bone morphogenetic
      proteins (BMP-2 and BMP-4). Similar temporo-spatial patterns of apoptosis and
      expression of BMP, specifically confined to the epithelium of the rudimentary
      tooth primordia, strongly support involvement of BMPs in the regulation of
      epithelial apoptosis during odontogenesis.

PMID- 9584915
TI  - Influence of low frequency magnetic fields on the intra-oral release of mercury
      vapor from amalgam restorations.
AB  - Since the results of a preliminary study have shown that the magnetic fields of
      some visual display units (VDUs) increased the release of mercury from amalgam
      specimens, the aim of the present study was to examine whether exposure to
      magnetic fields might affect the mercury vapor release from amalgam restorations
      in humans. The test group consisted of five subjects with an average of 31.4
      amalgam surfaces (range 13-48). In each of the subjects tested, the intra-oral
      release of mercury vapor was measured during three 9-h periods at intervals of 30
      to 90 min, using a standardized schedule and standardized food. During the first
      9-h period which served as control, no intentional magnetic fields were applied.
      During the second and the third 9-h period, magnetic fields with flux densities
      of 20 microT at 30 kHz or 500 microT at 50 Hz, respectively, were applied.
      Although these flux densities were one thousand times higher than those caused by
      VDUs, no effects could be found on the release of mercury vapor from the amalgam
      restorations. The results of the present study do not support the assumption that
      exposure to magnetic fields increases the mercury vapor release from amalgam
      restorations in humans.

PMID- 9584916
TI  - Cerebral oximetry--techniques.
AB  - The use of techniques to measure cerebral oxygen saturation is gradually gaining
      wide popularity. The main methods available today can mainly be classified as
      invasive or noninvasive. The invasive technology uses the parenchyma probes,
      which measure oxygen and biochemical parameters, depending upon the type of probe
      used. The noninvasive techniques use near infrared spectroscopy for transcranial
      cerebral oximetry. At present there is no universally accepted indication for the
      use of either technique but with time and wider use they are expected to become
      better understood. We discuss our experience and the techniques used in cerebral
      oximetry.

PMID- 9584917
TI  - Physiological steal around AVMs of the brain is not equivalent to cortical
      ischemia.
AB  - To challenge the concept of steal rendering the surrounding cortex ischemic, we
      examined patterns of nutritive capillary flow in the vicinity of AVMs. With a
      spectrophotometer (EMPHO, BGT) capillary O2 saturation (O2 satn.) was
      intraoperatively scanned around AVMs in n = 44 patients and in n = 42 controls.
      130,000 O2 satn. values before AVM resection were calculated as medians, ratio of
      critical values (< 25% O2 satn.), coefficients of variance and compared via ANOVA
      (p < 0.05). n = 40 AVM patients had no postoperative complication (group A),
      while in n = 4 cases a hyperperfusion syndrome occurred (group B). Physiological
      variables were comparable among groups A, B and C (controls). Medians (A: 52.9+/
      16.3, B: 44.2+/-17.1, C: 51.9+/-11.5% O2 satn.) and the ratio of critical values
      (A: 6.5+/-5.1, B: 14.7+/-11.1, C: 7.1+/-4.9 O2 satn.) were identical in groups A
      and C, but significantly different in group B, indicating exhausted compensation.
      Decreased flow heterogeneity in group A (A: 20.2+/-12.7, B: 27.9+/-12.4, C:
      26.8+/-10.9 O2 satn.) kept median cortical perfusion identical to group C. These
      results confirm recent findings, that cerebrovascular adaption by capillary
      recruitment keeps CBF at normal levels in the majority of cases and that chronic
      noninfarctional cerebral hypoperfusion is eventually the equivalent of steal
      around AVMs. Only around AVMs predisposed to hemodynamic derangement some areas
      of local low flow anoxia may exist.

PMID- 9584918
TI  - Resolving extra- and intracranial signal changes during adult near infrared
      spectroscopy.
AB  - Extracranial tissues have a significant effect on cerebral near infrared
      spectroscopy (NIRS) measurements in adults. Carotid surgery provides the
      opportunity to determine the relative contributions from the intra- and
      extracranial vascular territories. To assist, a specifically gated Laser Doppler
      flowmetry probe can be inserted between the NIRS optodes to co-monitor cutaneous
      blood flow associated with external carotid artery (ECA) clamping, whilst
      transcranial Doppler can be employed to monitor relative changes in the
      intracranial blood flow seen during internal carotid artery (ICA) clamping.
      Established criteria for severe cerebral ischemia (SCI) following carotid cross
      clamping was applied to 703 consecutive patients undergoing carotid surgery for
      high grade stenosis. Ipsilateral frontal NIRS recorded the difference (Total
      deltaHbdiff) in concentrations of oxy- and deoxy-hemoglobin. Interrupted time
      series analysis following clamping of the ECA and ICA allowed the different
      vascular components of Total-deltaHbdiff (ECA-deltaHbdiff and ICA-deltaHbdiff) to
      be identified. Data from 76 patients was suitable. Sixteen (21%) patients
      fulfilled the criteria for SCI. Patients who demonstrated an ICA-deltaHbdiff of >
      6.8 micromol l(-1) all showed SCI. No patient with an ICA-deltaHbdiff < 5.0
      micromol l(-1) showed SCI. Thus an ICA-deltaHbdiff threshold of 6.8 micromol l(
      1) provided a 100% specificity for SCI, whereas an ICA-deltaHbdiff < 5.0 micromol
      l(-1) was 100% sensitive for excluding SCI. When Total-deltaHbdiff was used
      without removing the ECA component, thresholds for SCI could not be resolved.
      NIRS can provide quantified thresholds for severe ischemia in the adult brain
      provided the extracranial component is removed.

PMID- 9584919
TI  - Near-infrared reflected spectroscopy and electroencephalography during carotid
      endarterectomy--in search of a new shunt criterion.
AB  - The aim of this clinical study was to evaluate cerebral oximetry with near
      infrared reflected spectroscopy (NIRS) as a monitoring system during carotid
      endarterectomy. The cross-clamping changes of cerebrovascular hemoglobin oxygen
      saturation (cereb. O2 satn.) were compared with data from a processed EEG
      analysis. Using the EEG as the gold standard we try to define a new shunt
      criterion based on near-infrared spectroscopy. 102 patients were studied. During
      cross-clamping the percentual decrease of cereb. O2 satn. was calculated. The
      relation between EEG and cereb. O2 satn. is described in terms of sensitivity and
      specificity, and is graphically shown in a Receiver Operator Characteristic (ROC)
      curve. At a cut-off value of 5% decrease or more for the cereb. O2 satn., a
      sensitivity of 100% was found. However, the specificity was only 44%. Higher cut
      off values resulted in a gradual increase of the specificity at the expense of a
      significant decrease of the sensitivity. In conclusion, improved validation and
      calibration techniques are necessary before this technique may be used for
      relevant assessment of cerebral oxygenation during carotid surgery. In
      particular, in order to define a new shunt criterion, the focal aspect of this
      new technique is probably one of the limitations.

PMID- 9584920
TI  - Effects of acupuncture on the oxygenation of cerebral tissue.
AB  - Monitoring of regional cerebral oxygen saturation (r. cereb. O2 satn.) was
      carried out continuously in 12 healthy subjects (mean age 35.2 +/- 4.4 years;
      range 26-41 years; 4 women, 8 men), prior to, during and following acupuncture.
      Measurements were obtained with the INVOS 3100 cerebral oximeter (Somanetics
      Corp., Troy, USA). In addition new robotic transcranial Doppler sonography (TCD)
      probes enabling three-dimensional imaging of the middle cerebral artery by the
      use of multi-scan techniques were used simultaneously. The results showed small
      increases in r. cereb. O2 satn. mean values (69.9% before, 70.3% during and 70.2%
      after acupuncture) and a significant (p < 0.01; ANOVA, Tukey test) increase in
      mean bloodflow velocity during acupuncture measured simultaneously at different
      depths within the right middle cerebral artery. There are reports in the
      literature about the effects of acupuncture on the oxygenation of cerebral tissue
      in a study with animals. An increase in the cerebral oxygen saturation could be
      registered with the help of microelectrodes in the cortex. This is parallel
      evidence to the present results with near infrared spectroscopy and transcranial
      Doppler sonography. Quantifiable changes in the physiological effects of
      acupuncture may contribute to improved acceptance of this unconventional
      complementary medical procedure.

PMID- 9584921
TI  - Cerebral oxygenation and the recoverable brain.
AB  - Oxygenation is the most critical function of blood flow and a sudden reduction in
      oxygen availability is an inevitable consequence of severe ischemia. The
      resulting cascade of events may result in the failure of membrane integrity of
      some cells and necrosis, but in the surrounding zone of tissue, less affected by
      hypoxia, cells survive to form the ischemic penumbra. The timing of these events
      is uncertain, but sufficient oxygen is available to these cells to maintain
      membrane ion pump mechanisms, but not enough for them to generate action
      potentials and therefore function as neurons. The existence of such areas has
      been suspected for some time based upon the nature of clinical recovery, but has
      now been demonstrated by SPECT imaging with a high plasma oxygen concentration
      under hyperbaric conditions as a tracer. A course of hyperbaric oxygen therapy
      frequently results in a permanent improvement in both flow and metabolism. These
      changes apparently represent a reversal of the changes that render neurones
      dormant and the activity of cells, previously undetectable by standard
      electrophysiological methods, can now be demonstrated. Three patients are
      presented in whom recoverable brain tissue has been identified using SPECT
      imaging and increased cerebral oxygenation under hyperbaric conditions. Improved
      perfusion from reoxygenation has correlated with clinical evidence of benefit
      especially with continued therapy.

PMID- 9584922
TI  - Oxygen consumption and energy state in an in vitro model of rat brain perfused
      with artificial oxygen carrier.
AB  - The present study was performed in order to determine the oxygen consumption of a
      rat brain perfused with an artificial oxygen carrier. Measurements were performed
      prior to and 2 or 30 min after an ischemic period of 5 min. In addition, the
      energy-related metabolites were determined. Basal oxygen consumption and energy
      state were comparable to in vivo conditions. The tissue concentration of the
      energy metabolites decreased during ischemia and completely recovered during 30
      min of reperfusion. The oxygen consumption was higher in the early phase of
      reperfusion than under pre-ischemic conditions. However, the oxygen consumption
      in the later phase of reperfusion was lower than the basal consumption. The data
      demonstrate that the addition of an artificial oxygen carrier to the perfusate
      provides sufficient amounts of oxygen to the in vitro preparation and that the
      measurement of the oxygen consumption during the post-ischemic reperfusion is a
      more sensitive parameter for the detection of emerging deficits than the
      measurement of the tissue levels of the energy metabolites.

PMID- 9584924
TI  - Cerebral blood flow and tissue oxygenation monitoring during aneurysm surgery.
AB  - Regional cerebral blood flow may be compromised during aneurysm surgery. This may
      occur during vessel occlusion by temporary clips or result from malposition of
      the definitive aneurysm clip. Post-operative cerebral vasospasm may also
      compromise cerebral blood flow and is an important cause of morbidity. This study
      addresses the need for a sensitive indicator of compromised cerebral function
      during aneurysm surgery by measuring brain tissue oxygenation and laser Doppler
      flow. Four patients were studied, all of whom had ruptured middle cerebral artery
      aneurysms. Brain tissue oxygenation measurements were made with a closed
      polarographic sensor placed in the ipsilateral cerebral hemisphere to the
      aneurysm. A laser Doppler flow probe and intracranial pressure monitor were
      similarly placed. The data were simultaneously processed using multimodality
      recording monitoring. The monitoring was continued during the post-operative
      period and totalled over 190 hours. Data were analysed as specific events and as
      trends. Initial tissue oxygen levels were low but improved in all cases as the
      intracranial pressure was reduced. This effect was independent of the cerebral
      perfusion pressure. Laser Doppler flow provided an indicator of compromised brain
      function and tissue oxygenation an indicator of established ischemia.

PMID- 9584923
TI  - Assessment of brain perfusion in coma and comparison between SPECT and CT scan
      data: preliminary report.
AB  - In this study we submitted 24 comatose patients (Glasgow Coma Score <8) to Single
      Photon Emission Tomography (SPECT) during the clinical course of coma to verify
      its utility and the relationship between SPECT and CT scan data. SPECT was
      recorded following i.v. injection of Xe-133 in 17 patients and of Tc-99m-HMPAO or
      Tc-99m-ECD in the remaining 7. SPECT data recorded during the acute phase of coma
      did not show a clear correlation between cerebral blood flow (CBF) and outcome.
      SPECT and CT scan detected abnormalities in the same areas in 6 cases (25%); 6
      patients (25%) with focal CT-scan lesions showed no focal CBF alterations in the
      same regions; conversely, in the remaining 12 cases (50%) SPECT disclosed severe
      perfusion abnormalities where no lesions were detectable on CT-scan. SPECT
      allowed us to recognize different regional flow patterns, such as absolute or
      relative hyperemia or oligoemia, which could not be checked with other means,
      thus improving patient's management. Apart from cerebral ischemia, there was no
      relationship between lesions on CT-scan and flow pattern. Our preliminary results
      suggest that SPECT can improve both the knowledge of patient's neurological
      conditions and management in comparison to the use of only CT scan.

PMID- 9584925
TI  - Low brain tissue oxygen pressure: incidence and corrective therapies.
AB  - In 16 head injured patients, the monitoring of brain tissue oxygen pressure (ti
      pO2) show 22 episodes of low ti-pO2 (< or = 12 mmHg). Mean episode duration was
      16 h. At time of the lowest ti-pO2 value, cerebral perfusion pressure (CPP), was
      < 60 mmHg in 5 cases, 4 of them with impending brain death. Oxygen saturation
      values of the jugular venous blood (svjO2) remained in the normal range (55-85
      mmHg) in 12 cases and exceeded 85 mmHg in 3 cases, 2 of them with impending brain
      death. Lactate-oxygen index (LOI) was normal (< 0.08) in 7/10 cases and at very
      high level (> 0.60) in 3 cases including 2 cases of impending brain death. A
      first group of low ti-pO2 episodes was clearly related to an insufficient CPP
      level (n = 13), comprising 4 cases of parallel decrease in CPP and ti-pO2 until
      brain death, and 9 cases in which ti-pO2 was restored along with a significant
      increase in CPP (p < 0.001). In 5 patients, low ti-pO2 episodes were due to
      another cause: vasospasm (2 cases), hypoxemia, anemia and premature interruption
      of anesthesia. Appropriate treatments were effective in restoring ti-pO2 with no
      change in CPP. In 4 patients, the cause of low ti-pO2 was not identifiable and
      episodes resolved spontaneously. The results confirm the critical influence of
      CPP and ti-pO2. Patients in whom elevation of CPP improved ti-pO2 have normal
      range CPP during the episode. Optimal CPP should therefore be sometimes higher
      than recommended. ti-pO2 monitoring appears a good method to define the optimal
      CPP level in individual patient. The duration of the artefactual period after
      catheter placement is to clarify.

PMID- 9584926
TI  - Hypothermia influences time course of intracranial pressure, brain temperature,
      EEG and microcirculation during ischemia-reperfusion.
AB  - Time-related effects of hypothermia on intracranial pressure (ICP), brain (Tbr)
      and rectal temperature (Tc), cortical (LDF) and subcortical microcirculation (ti
      pO2) were assessed following a unilateral balloon induced epidural focal mass
      lesion in rats. Results of injured but normothermia animals (Group A, n = 6) were
      compared with hypothermia animals (Group B, n = 6). Parameters were recorded
      during balloon expansion (BE) to an ICP of 60 mmHg followed by a period of
      sustained inflation (SI) of 30+/-2 min. Animals in Group B were then cooled to
      31.7+/-0.4 degrees C (Tbr) during SI. After reperfusion animals were monitored
      178+/-4 min. The study protocol concluded with a rewarming phase of the
      hypothermic animals. Balloon expansion led to a Cushing response and flattening
      of the EEG. In both groups Tbr decreased during inflation of the balloon 0.5-0.8
      degrees C below Tc and during SI in Group A 1.7 degrees C below Tc. During SI and
      reperfusion Tbr decreased below Tc in Group A but remained above Tc in Group B (p
      < 0.003). During sustained inflation LDF decreased in group A to 21% and in Group
      B to 45% of baseline values. After 178+/-4 min of reperfusion LDF reached 68% of
      baseline values in Group A and 97% in Group B (p < 0.001). During sustained
      inflation ti-pO2 showed median values of 0.8 mmHg in Group A and 5.5 mmHg in
      Group B. After reperfusion ti-pO2 reached normal values in both groups (p < 0.3)
      but ti-pO2 showed 18% higher values before rewarming. After reperfusion the
      secondary increase of ICP was reduced (p < 0.006) and CPP was improved by 20% in
      Group B. EEG restored quicker in Group B than Group A (106+/-11 min vs. 188+/-25
      min). Intra-ischemic hypothermia improved cerebral microcirculation, prevented a
      secondary increase of ICP and improved restoration of EEG after ischemia
      reperfusion.

PMID- 9584927
TI  - Hypothermia as cerebroprotective measure. Experimental hypoxic exposure of brain
      slices and clinical application in critically reduced cerebral perfusion
      pressure.
AB  - An in vitro human neocortical and rodent hippocampus brain slice technique was
      used under repeated hypoxia to investigate the cerebroprotective effect of
      hypothermia. As a hallmark of the neuronal hypoxic reaction anoxic terminal
      negativity (ATN) was registered to test whether hypothermia delays the onset of
      ATN. The experiments clearly confirm an assumed protective effect of hypothermia
      in vitro and in vivo and give for the first time evidence of the lack of the
      protective effect of hypothermia once hypoxia has occurred under normothermic
      conditions, probably by a critical depletion of cellular ATP-stores. In patients
      with severe traumatic brain injury and critically low cerebral perfusion pressure
      mild hypothermia is able to improve clinical outcome.

PMID- 9584928
TI  - The effect of different ventilation regimes on jugular venous oxygen saturation
      in elective neurosurgical patients.
AB  - Since the concept of hyperventilation on neurosurgical and neurotraumatological
      patients has been contested, our analysis was aimed at its scrutiny on the basis
      of easily accessible parameters of perisurgical monitoring. Furthermore, the
      influence of an improved oxygen supply was tested on hyperventilationally induced
      cerebral changes and to what extent recommendations could be derived for clinical
      application. In 50 patients (normoventilation FiO2 = 0.4, 0.6; moderate
      hyperventilation up to a value of paCO2 = 31 mmHg and FiO2 = 0.4, 0.6 and 0.8),
      who underwent an elective neurosurgical operation at the central nervous system,
      a fiberoptical catheter was inserted into the bulb of the jugular vein for the
      continuous monitoring of the jugular venous oxygen saturation (sjvO2),
      additionally to the regular measures of perioperative monitoring. Approval for
      this study was given by the Ethics Committee of the University of Leipzig. At
      five defined times an analysis of arterial and jugular venous blood gas samples
      was made and their lactate and glucose concentration determined: 1. Immediately
      after inducing anesthesia; 2. After dura opening; 3. Sixty minutes after dura
      opening; 4. At dura closing; 5. Sixty minutes after the end of the operation. The
      lactate oxygen index (LOI) as well as the cerebral oxygen extraction (CEO2) were
      calculated from primary data. Hyperventilation with a value of FiO2 = 0.4 leads
      to a significant decrease of the jugular venous oxygen saturation below 55%. It
      can be positively influenced by increasing the inspiratory oxygen concentration
      from 40% to 60%. The CEO2 increases, above values of 42% under a hyperventilation
      of FiO2 = 0.4. This effect can be reversed by increasing the FiO2 value up to
      0.6. Under hyperventilation the LOI reaches 'pre-ischemic' values (LOI > 0.03)
      prior to dura opening. Further decrease of FiO2 to 0.8 has no positive additional
      effect. Normoventilation with FiO2 = 0.6 induces a decrease of sjvO2 but also a
      decrease of LOI. Hyperventilation as a routine procedure during elective
      neurosurgery shall be applied critically and be combined with an increased
      inspiratory oxygen concentration if necessary. A longterm normoventilation with
      increased FiO2 should be avoided.

PMID- 9584929
TI  - Brain tissue pO2 and outcome after severe head injury.
AB  - Although the use of on-line monitoring of brain ti-pO2 is increasing, so far the
      critical level of 10 mmHg is derived from animal experiments and clinical
      analyses: no hard proof on outcome basis has been given until now. The authors
      present an outcome analysis of 35 patients with severe head injury. Inclusion
      criteria were: start of ti-pO2 monitoring < or = 40 h post-injury, the probe
      lying in CT scan normal tissue and the GOS at 6 months being available. The good
      outcome group (GOS 4 + 5, n = 17) showed a 17.7+/-9.1 h delay from the injury to
      the monitoring compared to the bad outcome group (GOS 1-3, n = 18) with (14.2+/
      9.1 h) (p < 0.05). Age and initial Glasgow Coma Score were not different. In the
      bad outcome group there were more patients with a diffuse injury type 3 and 4.
      The distribution of the ti-pO2 values show in all the examined time intervals
      (day 0-6, 0-72 h, 0-48 h and 0-24 h) a left shift in the bad outcome group with
      most pronounced difference for ti-pO2 < or = 10 mmHg. For the period from 0-48 h
      and even more from 0-24 h post-injury, the difference between both groups was
      significant (p = 0.036 and p = 0.013). In the bad outcome group 35.5% of the
      values from 0-24 h were < 10mmHg (compared to 10.6% in the good outcome group. ti
      pO2 values > or = 50 mmHg were seen more often in the bad outcome group; this
      occurred mainly after 48-72 h post-injury. The authors concluded that brain ti
      pO2 monitoring is able to detect the occurrence of early hypoxic insults. Brain
      ti-pO2 monitoring is an important parameter in the multimodality monitoring
      system.

PMID- 9584930
TI  - Multiparametric monitoring of brain oxygen balance under experimental and
      clinical conditions.
AB  - In order to evaluate the relationship between brain oxygen supply and demand (O2
      balance) in real time, it is necessary to use a multiparametric monitoring
      approach. Cerebral blood flow (CBF) is a representative parameter of O2 supply.
      The extracellular level of K+ is a reliable indicator of O2 demand since more
      than 60% of the energy consumed by the brain is utilized by active transport
      processes. Mitochondrial NADH redox state can represent the balance between O2
      supply and demand. In order to monitor the brain of experimental animals or
      patients, we constructed the multiparametric assembly (MPA) and the following
      parameters were monitored simultaneously and in real time: CBF, CBV, NADH redox
      state, extracellular K+, DC potential, EEG, tissue temperature and ICP. Animals
      were exposed to hypoxia, ischemia, hypercapnia, hyperoxia and spreading
      depression (SD) and the relative changes in CBF and NADH were calculated and
      found to be significant indicators of brain energy state. Monitoring these two
      parameters increases the possibility of differentiating between various
      pathophysiological states. Each added parameter increases the power of diagnosis
      and determination of the functional state of the brain. Preliminary results
      obtained in patients monitored in the ICU or in the OR show that the responses to
      hypercapnia, spreading depression or ischemia are similar to those measured in
      experimental animals.

PMID- 9584931
TI  - Regional tissue pO2, pCO2, pH and temperature measurement.
AB  - We compared the difference in brain tissue oxygen pressure (pO2), carbon dioxide
      pressure (pCO2), pH and temperature with 2 probes inserted 1 cm apart, in 7
      patients. Following a craniotomy for cerebrovascular surgery, two Neurotrend
      probes which measure pO2, pCO2, pH and temperature were inserted into the brain 1
      cm apart. Measures were compared between the probes under baseline anesthetic
      conditions and during the course of surgery. Under baseline conditions, tissue
      pO2, pCO2, pH and temperature were not different between the 2 probes. A
      significant correlation was seen between the probes in pH and temperature. During
      the course of surgery, variation in tissue gases and pH occurred with changes in
      ventilation and blood pressure but the difference between the probes remained
      stable. Ischemic changes in pO2, pCO2 and pH were seen in one of the 2 probes
      during brain artery occlusion or retractor placement. These results show that
      tissue pO2, pCO2 and pH are consistent in local brain regions during steady state
      conditions. The relationship between local measures is disrupted by regional
      ischemia.

PMID- 9584933
TI  - Metabolic changes in the brain during transient ischemia measured with
      microdialysis.
AB  - Forty-four patients with severe head injury were monitored for episodes of
      cerebral ischemia using jugular venous oxygen saturation (sjvO2), brain tissue
      pO2 (ti-pO2), and a microdialysis probe. The concentration of lactate and glucose
      were measured in the microdialysate. A total of 10 episodes of global ischemia
      were observed. The characteristic pattern of a simultaneous decrease in sjvO2 and
      brain ti-pO2 with an increase in the concentration of lactate occurred in all 10
      patients. In addition, 3 episodes of regional ischemia were observed. Although
      brain ti-pO2 decreased to very low values and the concentration of lactate
      increased in the microdialysate, sjvO2 remained unchanged. Brain ti-pO2 adds
      another dimension to our cerebral monitoring by allowing the detection of
      regional cerebral ischemia.

PMID- 9584932
TI  - Extended neuromonitoring: new therapeutic opportunities?
AB  - In order to optimize therapy for the injured brain it is desirable to
      continuously monitor substrate delivery in the critically ill patient.
      Interruption of substrate delivery is a major factor of the great vulnerability
      to ischemic damage, which affects a majority of patients after severe head
      injury, stroke or subarachnoid hemorrhage. An approach to protecting the brain
      during ischemia is to increase the delivery of oxygen via residual blood flow
      through ischemic tissue. Hypothermia is also an important means of protecting
      brain cells from the deleterious effects of ischemia, after severe head injury,
      because it reduces metabolic demands. In this study we continuously measured
      brain oxygen, brain CO2, brain pH and brain temperature, as well as hourly brain
      glucose and lactate. A multiparameter sensor was inserted into brain tissue, via
      a three lumen bolt, along with a ventriculostomy catheter and a microdialysis
      probe in 60 severely head injured patients. Brain oxygen delivery was increased
      by stepwise increase of inspired oxygen (FiO2) from 30% to 60% to 100% over a
      period of 6 h, in order to test the effect of enhanced oxygen tension, on tissue
      oxygen. In most patients brain oxygen was initially low, and progressively
      increased, over the monitoring period, to a steady state level, around 30-40
      mmHg. In those who died or remained vegetative, brain oxygen fell to anerobic
      levels. Episodes of increased ICP (n = 25), hypotension (n = 15), and respiratory
      difficulties (n = 9) caused an immediate increase in brain CO2. Multiple logistic
      regression analysis showed brain oxygen to be the strongest predictor for outcome
      in these patients. By increasing FiO2, an increase in oxygen delivery of more
      than 100%, and a simultaneous decline in lactate production was seen (p < 0.01).
      Brain temperature was closely related to rectal temperature, brain oxygen, and
      cerebral blood flow. Patients who were spontaneously hypothermic had a poor
      outcome (p < 0.01). A fuller understanding of dynamic factors affecting brain
      metabolism and substrate delivery may be obtained with extended neuromonitoring.

PMID- 9584934
TI  - Reasoning about moral aspects of illness and treatment by preschoolers who are
      healthy or who have a chronic illness.
AB  - Our study evaluates the moral reasoning skills of healthy and chronically ill 3
      and 4 year olds with respect to illness and treatment, by use of an interview
      technique that reduces verbal demands on the child. We presented children with
      pairs of scenarios comparing ill characters with characters acting immorally and
      characters being punished, as well as with pairs of scenarios comparing treated
      characters with characters acting immorally and characters being punished. We
      asked children to point to the character who did something "naughty." With the
      exception of the chronically ill 3 year olds, the children performed consistently
      above chance and did not confuse illness and immorality. Older and healthy
      children performed better than younger and chronically ill ones (differences were
      the result of differing receptive vocabulary skill levels). This research has
      implications for evaluating young children's reasoning abilities and suggests
      that medical professionals should use tools that reduce demands on children's
      verbal proficiency.

PMID- 9584935
TI  - Gender differences in ADHD?
AB  - This study examined possible gender differences in children and adults with
      attention-deficit/hyperactivity disorder. Results indicated that adult self
      ratings differed significantly by gender. Adult women reported fewer assets and
      more problems than did male counterparts, but there was no gender difference with
      respect to age at referral, intelligence quotient, indicators of
      neuropsychological performance, or parent or teacher ratings of behavior.
      Referral bias against girls is a possible reason for previously reported gender
      differences, so we interpreted our results in light of the participants' referral
      patterns. There was a nonsignificant trend for girls with relatively more severe
      ratings of hyperactivity, conduct disorder, or inattention to be referred earlier
      than were boys. Overall, our results suggest no evidence of cognitive or
      neuropsychological differences by gender in samples that are sensitive to
      behavioral deviance in girls (as evidenced by early referral), but adult women's
      self-perception is comparatively poorer than that of adult men.

PMID- 9584936
TI  - Risk factors associated with infant death among very low birth weight infants
      after discharge from an intensive care nursery.
AB  - Low birth weight infants have an increased incidence of death after discharge
      from the intensive care nursery (ICN). To evaluate factors associated with death,
      and especially unexpected death, we conducted a study on 724 infants discharged
      from our ICN with a birth weight 1500 g or less. Twenty-four infants died during
      the 1st year after discharge. Univariate analyses and logistic regression
      analyses were used to examine the effects of birth weight, gestational age, race,
      gender, growth retardation, chronic lung disease (CLD), intracranial hemorrhage
      (ICH), and socioeconomic risk on postdischarge death. Of the risk factors
      studied, only CLD (p = .001) and ICH (p = .004) were independently associated
      with death, but ICH alone was the most worrisome risk factor associated with
      sudden, unexpected death in low birth weight infants after discharge from an ICN.

PMID- 9584937
TI  - The neonatal withdrawal inventory: a simplified score of newborn withdrawal.
AB  - A new method for the rapid assessment of neonatal withdrawal was tested. Three
      studies with 80 newborns compared the reliability, sensitivity and specificity of
      the Neonatal Withdrawal Inventory (NWI) with that of the Neonatal Abstinence
      Scoring System (NASS), a widely used neonatal withdrawal scale. Interrater
      reliability for raters assessing neonatal withdrawal with the NWI (range, 0.89
      0.98) was superior to that demonstrated by the same raters using the NASS (range,
      0.70-0.88). With the NASS as the standard, the sensitivity and specificity of the
      NWI were 100% at syndrome detection and treatment threshold levels. With use of
      the NWI, the severity of neonatal withdrawal could be accurately assessed in 10
      minutes under case-blinded conditions. The NWI's advantages include brevity, ease
      of administration, and flexibility. The NWI's simplicity and accuracy commend its
      wider use as a clinical and experimental tool.

PMID- 9584938
TI  - An ADHD educational intervention for elementary schoolteachers: a pilot study.
AB  - We assessed the effect of pediatrician-led inservice training on the knowledge
      and stress of elementary schoolteachers related to attention
      deficit/hyperactivity disorder (ADHD). The subjects were 44 schoolteachers
      staffing a 750-student school. Preintervention and postintervention
      questionnaires assessed teachers' training and knowledge concerning ADHD, teacher
      stress, and teacher-rated student behavior. The intervention was an ADHD
      curriculum developed by the national organization, Children and Adults with
      Attention-Deficit Disorder (CHADD). At preintervention, 41% of the teachers
      thought that ADHD could be caused by poor parenting and 41%, by sugar or food
      additives; 64% thought that methylphenidate should be used only as a last resort.
      Postintervention percentages of teachers holding these beliefs were 7%, 5%, and
      34%, respectively. Sixty-one percent had no contact with physicians prescribing
      stimulants. Teacher stress correlated with ADHD behavior in male students and
      decreased postintervention. Use of the CHADD curriculum and discussion with a
      pediatrician were associated with improved teacher knowledge and decreased
      teacher stress related to ADHD.

PMID- 9584939
TI  - The pediatrician as therapist I: psychoanalytic psychotherapy.

PMID- 9584940
TI  - Diurnal and nocturnal enuresis in a 6 year old.
AB  - Justin is a 6-year-old boy diagnosed with attention-deficit/hyperactivity
      disorder who presented with daytime and night-time wetting. He had been toilet
      trained at the age of 3 years but was back in diapers as a result of the
      enuresis. His bowel movements were normal. The initial evaluation consisted of a
      urinalysis, urine culture, serum creatinine level, and renal/bladder ultrasound
      examination. The urine studies were normal. The serum creatinine level was
      elevated at 1.0 mg/dL. The ultrasound examination revealed bilateral mild
      hydronephrosis and a thickened bladder wall. A voiding cystourethrogram was
      ordered to evaluate anatomy, but Justin would not allow a Foley catheter to be
      inserted, so the procedure, along with cystoscopy, was performed under
      anesthesia. Cystoscopy revealed a highly trabeculated bladder, as is seen in
      either high-grade obstruction or a neurogenic bladder. The cystogram did not show
      any obstruction or vesicoureteral reflux. Meanwhile, Justin's symptoms continued
      to increase to the point at which he was constantly wet, and he no longer made
      any attempts to void on his own. A spinal magnetic resonance imaging study did
      not show any occult neurologic lesions. Urodynamic studies revealed a high
      pressure bladder, poor emptying, and inappropriate voluntary contraction of the
      striated, urinary sphincter during micturition. Despite institution of
      anticholinergic medication, psychotherapy, and behavioral therapy, Justin
      continued to do poorly. He could not tolerate clean intermittent catheterization,
      and he eventually required a suprapubic tube for urinary drainage and
      preservation of his kidneys.

PMID- 9584941
TI  - Recurrent pediatric headaches: assessment and intervention.
AB  - Assessment and intervention issues in recurrent pediatric headache are discussed.
      A broad overview of diagnostic and etiological issues is presented, with
      consideration of the application of functional models to recurrent headache
      patterns. Behavioral treatment outcome research is reviewed, and pharmacotherapy
      approaches are briefly addressed. Recommendations are made for clinical practice,
      and future research priorities in the area of recurrent pediatric headache are
      underscored.

PMID- 9584942
TI  - Neurogenetics in developmental and behavioral pediatrics: advances in molecular
      diagnosis.
AB  - The discovery and characterization of thousands of genes involved in human
      disorders has the potential for great benefit in patient diagnosis and treatment.
      A combined approach using molecular genetic testing for some disorders as an
      adjunct to the clinical evaluation of children with developmental or behavioral
      features is rapidly occupying a more prominent role in the diagnostic evaluation.
      In some instances, molecular testing might confirm a genetic etiology in a child
      initially referred with a DSM-IV diagnosis, but molecular testing might be of
      limited use in other instances. This review presents advances in the diagnosis of
      inherited disorders affecting the pediatric population, with an emphasis on those
      with a developmental/behavioral component. We examine several relatively common
      disorders in detail (and less common disorders in a more cursory fashion) to
      elucidate the strengths and weaknesses of molecular diagnosis in clinical
      practice.

PMID- 9584943
TI  - Some reproductive studies in the baboon.
AB  - A captive colony of baboons has been used for three decades for various
      reproductive studies where application of findings to human therapeutics was
      desired. The characteristics of the menstrual cycle in baboons are very similar
      to those of women, except that of the baboon is slightly longer and there is a
      lower luteal phase concentration of oestradiol. The duration of pregnancy in
      baboons is about two-thirds that of humans but patterns of oestrogen and
      progesterone secretion are virtually identical. The principal oestrogen produced
      by the pregnant baboon is oestrone, while oestriol is the most abundant in human
      pregnancies. Chorionic gonadotrophin (CG) is elevated significantly only in the
      first trimester of a baboon pregnancy, while human pregnancy concentrations of
      this hormone are about one-third of the first trimester level in the second and
      third trimesters. Breeding success of baboons in captivity depends on care being
      taken to cull infertile animals from the colony prior to commencing matings.
      Under optimal conditions, fertility rates can reach nearly 80%. Female baboons
      have been successfully used to gain insights into antifertility effects of
      contraceptive vaccines directed against CG, spermatozoa and ovum antigens.
      Extensive use of the colony for developing a human chorionic gonadotrophin (HCG)
      antifertility vaccine has been invaluable for progress in this field. Other
      pharmaceuticals and devices have been successfully tested in baboons, but costs
      and mandated regulations for the management of these nonhuman primates have made
      their current use in meaningful studies extremely difficult.

PMID- 9584944
TI  - The baboon oviduct: characteristics of an oestradiol-dependent oviduct-specific
      glycoprotein.
AB  - The baboon oviductal epithelium differentiates into a tall columnar epithelium
      consisting of ciliated and secretory cells during the follicular phase of the
      menstrual cycle in response to rising oestradiol levels. The apical tips of these
      secretory cells are filled with membrane-bound secretory granules. During the
      luteal phase when progesterone levels are elevated, the epithelium regresses and
      deciliation occurs. Analysis of secretory proteins obtained from explant culture
      media by SDS-PAGE followed by fluorography or Western blots has revealed that the
      baboon oviduct synthesizes and secretes a high molecular weight glycoprotein
      during the follicular phase of the cycle. Immunocytochemistry demonstrated that
      this oviductal glycoprotein is localized to the secretory granules of epithelial
      secretory cells, is oviduct specific, and that following secretion the oviductal
      glycoprotein binds to the zona pellucida and perivitelline space of ovulated
      oocytes and embryos within the oviduct. Similar proteins have been characterized
      in other mammalian species. cDNA data show that the complete coding sequence is
      2228 bp for a protein of 623 amino acids. A Genbank search showed that baboon
      oviductal glycoprotein has high homology to other oviductal glycoprotein
      sequences at both the nucleotide and amino acid levels. Studies conducted to date
      probing the biological function of oviductal glycoprotein indicate that this
      protein plays a role in prefertilization reproductive events (sperm capacitation;
      sperm-zona binding; zona penetration). Additional experiments are needed to
      reveal a specific function and mechanism for this molecule.

PMID- 9584945
TI  - Secretory proteins of the baboon (Papio anubis) endometrium: regulation during
      the menstrual cycle and early pregnancy.
AB  - The biological function of uterine endometrial secretory proteins in the primate
      remain to be elucidated. In general, during the luteal phase and under
      progesterone dominance, the glandular epithelial cells synthesize and secrete a
      number of proteins. Of these, placental protein 14 (PP14; now referred to as
      glycodelin) and insulin-like growth factor binding protein-1 (IGFBP-1) are the
      best characterized. Although induced by progesterone, their synthesis increases
      exponentially during pregnancy. In the baboon, glycodelin is immunolocalized to
      the mid functionalis and basal glands between days 10 and 12 post-ovulation. In
      response to either exogenous or blastocyst-secreted chorionic gonadotrophin,
      glandular synthesis increases markedly and remains elevated up to days 18-25 of
      pregnancy. The decrease in glycodelin in the endometrium is associated with
      glandular regression during the first third of pregnancy. In contrast, IGFBP-1 is
      only observed in the deep basal glands during the luteal phase. Following the
      establishment of pregnancy, IGFBP-1 synthesis switches from glandular to stromal
      and is correlated with the process of decidualization. IGFBP-1 synthesis
      continues to increase throughout gestation. We propose that glycodelin may have
      immunosuppressive properties and that IGFBP-1 may regulate trophoblast migration
      within the uterine endometrium.

PMID- 9584946
TI  - From blastocyst to placenta: the morphology of implantation in the baboon.
AB  - Implantation and placentation in the baboon share many morphological features
      with other primates, as well as having some specific distinctions. The ability to
      use deturgescence of the sex skin as a method of timing ovulation and the ease
      with which the uterine lumen can be flushed have been used to examine
      morphological aspects of blastocyst differentiation and implantation in this
      species. Preimplantation blastocysts were obtained by non-surgical flushing of
      the uterus 6-8 days after ovulation, and implantation sites were excised from
      uteri removed on days 10-16 of gestation. All tissues were prepared for electron
      microscopy by aldehyde fixation and plastic embedding. Maturation of trophoblast
      from the compacted morula stage to the expanded blastocyst stage includes
      increase in numbers of polyribosomes, changes in conformation of mitochondria,
      and development of an effective endocytic apparatus. An endodermal layer forms
      beneath the inner cell mass prior to loss of the zona pellucida, and parietal
      endodermal cells extend beyond the inner cell mass. Azonal blastocysts have
      regions of syncytial trophoblast adjacent to the inner cell mass, and they may
      represent adhesion stages of early implantation. In early postimplantation
      stages, trophoblast replaces the uterine epithelium and processes of syncytial
      trophoblast invade dilated superficial maternal vessels. In subsequent lacunar
      stages there is rapid elevation of the developing conceptus above the uterine
      surface as the lacunae enlarge. Cytotrophoblast rapidly enters maternal vessels,
      and arterioles are partially or completely occluded by migrating cytotrophoblast.
      The early access to controlled maternal blood flow apparently allows
      trophoblastic lacunae to expand superficially as opposed to more extensive
      endometrial invasion.

PMID- 9584947
TI  - Perspectives on the use of the baboon in embryology and teratology research.
AB  - This paper summarizes the developmental stages of the baboon during the period of
      organ formation and provides comparative information for other primates,
      including the human. Special attention is directed to the early development of
      the nervous system, eye, ear and nose/palate. The similarity in development of
      these structures with humans indicates that the baboon is a suitable model for
      studies of normal and abnormal neurological development. Spontaneous prenatal
      loss rates in the baboon (2.4-11.2%) are slightly lower than those reported in
      rhesus and cynomologus monkeys. The baboon, in addition to the cynomologus monkey
      and macaque, has been used as a model in teratology research to assess the
      potential risk of thalidomide, sex steroids, Bendectin and rubella virus, as well
      as to study the pathogenesis of malformations associated with the corticosteroid
      triamcinolone acetonide. The rate of spontaneous malformations (<1%) in baboons,
      similar to that reported for other commonly used primates, supports their
      continued use as a teratological model. In this regard, a sample protocol is
      provided for the safety evaluation of biotechnology products using nonhuman
      primates, which are the most appropriate model for those compounds which are
      bioactive in species closely related to humans.

PMID- 9584949
TI  - Surrogacy: review for the UK Health Ministers of current arrangements for
      payments and regulation.

PMID- 9584948
TI  - Consent and the law: review of the current provisions in the Human Fertilisation
      and Embryology Act 1990 for the UK Health Ministers.

PMID- 9584950
TI  - Report on cloning by the US Bioethics Advisory Commission: ethical
      considerations.

PMID- 9584951
TI  - Targeting gene therapy vectors to CNS malignancies.
AB  - Gene therapy offers significant advantages to the field of oncology with the
      addition of specifically and uniquely engineered mechanisms of halting malignant
      proliferation through cytotoxicity or reproductive arrest. To confer a true
      benefit to the therapeutic ratio (the relative toxicity to tumor compared to
      normal tissue) a vector or the transgene it carries must selectively affect or
      access tumor cells. Beyond the selective toxicities of many transgene products,
      which frequently parallel that of contemporary chemotherapeutic agents, lies the
      potential utility of targeting the vector. This review presents an overview of
      current and potential methods for designing vectors targeted to CNS malignancies
      through selective delivery, cell entry, transport or transcriptional regulation.
      The topic of delivery encompasses physical and pharmaceutic means of increasing
      the relative exposure of tumors to vector. Cell entry based methodologies are
      founded on increasing relative uptake of vector through the chemical or
      recombinant addition of ligand and antibody domains which selectively bind
      receptors expressed on target cells. Targeted transport involves the potential
      for using cells to selectively carry vectors or transgenes into tumors. Finally,
      promoter and enhancer systems are discussed which have potential for selectivity
      activating transcription to produce targeted transgene expression or vector
      propagation.

PMID- 9584952
TI  - The class III variant of the epidermal growth factor receptor (EGFRvIII):
      characterization and utilization as an immunotherapeutic target.
AB  - Any immunotherapeutic approach to cancer cell eradication is based upon the
      specific recognition of neoplastic cells and the sparing of surrounding normal
      tissue; perhaps nowhere is this distinction more important than within the
      central nervous system, due to the diffuse infiltrative nature of primary glial
      tumor cell growth. Whether ultimate effect moieties are immunoglobulins,
      fragments and/or their constructs with drugs, toxins, radionuclides, or immune
      cells, the specificity of effector: cell surface marker is crucial. This review
      describes the identification, immunologic characterization, and biologic behavior
      of a transmembrane tumor-specific altered growth factor receptor molecule which
      may well serve as a mediator of multiple immunotherapeutic approaches: the class
      III variant of the epidermal growth factor receptor, EGFRvIII.

PMID- 9584953
TI  - Transgenic mice as research tools in neurocarcinogenesis.
AB  - Transgenic animal models for neurocarcinogenesis have provided significant
      insights into the molecular mechanisms underlying carcinogenic processes,
      including those which affect the nervous system. In view of the very rapid pace
      of acquisition of knowledge, it is not possible to cover all transgenic mouse
      models for neural tumors. Instead, this article discusses some of the most
      important technical innovations for manipulation of the mammalian genome (notably
      the various methods for targeted genome modifications, as well as the technology
      for introducing large DNA fragments into the germ line of mice), and presents a
      selection of the transgenic mouse models which are proving most promising for
      furthering our understanding of the pathogenetic basis of cancer in the nervous
      system.

PMID- 9584954
TI  - Tumor pathogenesis of human neurotropic JC virus in the CNS.
AB  - In the last several years, studies have reported the detection of sequences
      similar to the polyomavirus, Simian Virus 40 (SV40) in human tumors including
      choroid plexus papillomas and ependymomas. Taken together with well-established
      evidence that SV40, as well as the human polyomaviruses JC virus (JCV) and BK
      virus (BKV), are oncogenic in several animal models, new interest has resurfaced
      regarding a possible role for these viruses in human tumors. In particular, a
      strong case can be made for re-evaluating the oncogenic potential of JCV in a
      neurotropic polyomavirus which is the causative agent of the fatal human
      demyelinating disease, Progressive Multifocal Leukoencephalopathy (PML). In this
      review, we discuss the transforming capability of JCV in vitro, JCV's ability to
      induce neural origin tumors in non-human primates as well as in rodents, and
      several case reports which suggest a possible role for JCV in tumor pathogenesis
      in the central nervous system.

PMID- 9584955
TI  - Sequence analyses of human tumor-associated SV40 DNAs and SV40 viral isolates
      from monkeys and humans.
AB  - SV40 DNA has been found associated with several types of human tumors. We now
      report a sequence comparison of SV40 DNAs from pediatric brain tumors and from
      osteosarcomas with viral isolates from monkeys and from humans. We analyzed the
      entire genomic sequences of five isolates, Baylor and VA45-54 strains from
      monkeys and SVCPC, SVMEN, and SVPML-1 recovered from humans, and compared them to
      the reference virus SV40-776. The viral sequences were highly conserved, but
      isolates could be distinguished by variations in the structure of the viral
      regulatory region and in the nucleotide sequence of the variable domain at the C
      terminus of the large T-antigen gene. We conclude that multiple strains of SV40
      exist that can be identified on the basis of sequences in these regions of the
      viral genome. The isolates were more similar to each other and to the Baylor
      strain than to the reference strain SV40-776. Human isolates SVCPC and SVMEN were
      found to be identical. The DNAs present in some human brain and bone tumors were
      authentic SV40 sequences. Many of the C-terminal T-ag sequences associated with
      human tumors were unique, but some sequences were shared by independent sources.
      There was no compelling evidence for human-specific strains of SV40 or for tumor
      type-specific associations, suggesting that SV40 has a relatively broad host
      range. The source of the viral DNA found in human tumors remains unknown.

PMID- 9584956
TI  - Immune parameters affecting adenoviral vector gene therapy in the brain.
AB  - Gene therapy utilizing replication deficient adenoviral vectors represents a
      potentially promising approach to the treatment of brain tumors. Limited duration
      of systemic transgene expression and inefficient transduction following repeat
      systemic vector administration secondary to an effective anti-vector immune
      response limits the potential application of first generation adenoviral vectors.
      Whether host immune responses will significantly limit the use of these vectors
      within the immunopriviledged environment of the central nervous system remains to
      be elucidated. Following a single intravenous injection of a beta-galactosidase
      expressing adenoviral vector (Ad.CMV-betagal), we found maximal betagal transgene
      expression in systemic sites (i.e. liver) at day 4, with almost complete
      disappearance by day 7. In contrast, significant beta-galactosidase activity was
      seen for greater than 28 days following a single intracerebral inoculum of virus.
      Rechallenge experiments demonstrated complete protection against repeat systemic
      vector administration, whereas intracerebral transgene expression was not
      affected by prior systemic or intracerebral exposure to adenoviruses. These data
      suggest that systemic anti-adenoviral vector immune responses are attenuated
      within the central nervous system and may not pose as significant a problem for
      the treatment of brain tumors as for other systemic indications.

PMID- 9584957
TI  - Principles of treatment of malignant gliomas in adults: an overview.
AB  - The cornerstone of conventional treatments of malignant gliomas in adults has
      been surgical debulking, radiation therapy and chemotherapy. Almost always a
      combination of these treatments is used. With these conventional treatments the
      outcome, as measured by survival and quality of life, has remained universally
      dismal. Novel treatments, which are at different stages of laboratory and
      clinical trials, may offer a ray of hope for treatment of malignant gliomas.
      Development of these methods are directly related to the discoveries, over the
      past two decades, of cellular and molecular mechanisms involved in the genesis of
      brain tumors. Understanding of the mechanisms of tumor genesis may open new
      avenues of effective treatments for this devastating cancer.

PMID- 9584958
TI  - Differentially expressed gene products in glioblastoma cells suppressed for
      tumorigenicity.
AB  - The loss of large segments or an entire copy of chromosome 10 is the most common
      genetic alteration in human glioblastomas. To address the biological and
      molecular consequences of this chromosomal alteration, we transferred a human
      chromosome 10 into a glioma cell clone devoid of an intact copy. The hybrid cells
      exhibited an altered cellular morphology, a decreased saturation density, and a
      suppression of both anchorage-independent growth and tumor formation in nude
      mice. The hybrids also expressed the recently identified candidate tumor
      suppressor gene MMAC1/PTEN. To further identify gene products that may be
      involved in glioma progression, a subtractive hybridization was performed between
      the human glioblastoma cells and the phenotypically suppressed hybrid cells to
      identify differentially expressed gene products. Sixty-one clones were
      identified, with nine clones being preferentially expressed in the hybrid cells.
      Four cDNA clones represented markers of differentiation in glial cells. Two cDNA
      clones shared homology with platelet derived growth factor-alpha and the insulin
      receptor, respectively, both genes previously implicated in glioma progression. A
      novel gene product that was expressed predominantly in the brain, but which did
      not map to chromosome 10, was also identified. This clone contained an element
      that was also present in three additional clones, two of which also exhibited
      differential expression. Consequently, the presence of a functional copy of
      chromosome 10 in the glioma cells results in differential expression of a number
      of gene products, including novel genes as well as those associated with glial
      cell differentiation.

PMID- 9584959
TI  - Management of malignant glioma: role of surgery in relation to multimodality
      therapy.
AB  - The goals of surgery for malignant glioma are to establish a histological
      diagnosis and to achieve mechanical cytoreduction to reduce intracranial pressure
      (ICP) and possibly alter tumor kinetics. There is controversy concerning the
      question whether the glioma is a focal or diffuse process; it appears that there
      may be variability between the two extremes in individual cases. The question of
      the value of surgery has also been controversial. Review of the literature
      suggests that both early and long-term postoperative outcome after radical
      surgical resection are better than the results of either partial resection or
      simple biopsy, in terms of neurological status and duration of survival.
      Similarly, reoperation for recurrence of glioma offers reasonable extension of
      quality survival. Despite the desirability of extensive cytoreductive surgery for
      malignant gliomas, the presence of viable infiltrative cells beyond the margins
      of the resection necessitate that surgery be a part of an aggressive
      multimodality therapeutic approach. Adjunctive measures to control the
      infiltrative component include newer forms of radiotherapy (such as stereotaxic
      radiosurgery) and newer delivery techniques for chemotherapy (agents impregnated
      in biodegradable polymers implanted in the tumor bed after surgical resection),
      and possibly immunotherapy and gene therapy as they may become feasible in the
      future. The strategy for management of malignant glioma thus consists of a
      combination of extensive surgical resection to reduce the accessible tumor
      burden, followed in rapid sequence by measures to control the infiltrative
      portion of the tumor. It is recommended that these measures be offered 'up front'
      rather than delaying treatment until there is clinical or radiographic evidence
      of tumor recurrence.

PMID- 9584960
TI  - Effects on brain tumor cell proliferation by an adenovirus vector that bears the
      interleukin-4 gene.
AB  - A recombinant adenovirus vector bearing the IL-4 gene (AD-IL-4) was used to
      infect rat glioma C6 cells in culture at multiplicity of infections (MOI) from 50
      to 1800. C6 cell proliferation was not altered significantly by adenoviral
      infection. However, IL-4 production increased in a dose-dependent manner. To
      ascertain effects on in vivo cell proliferation, a subcutaneous tumor model was
      used. Rat C6 glioma cells alone or C6 mixed with the control virus bearing the
      LacZ gene (Ad-LacZ) produced tumors that measured an average of approximately
      3000 mm3 35 days after implantation. In contrast, C6 cells mixed with Ad-IL-4
      produced significant inhibition of tumor growth (P=0.035 compared to C6 tumor;
      P=0.023 compared to C6+Ad-LacZ tumor. Student's ttest). IL-4 levels in mice serum
      were measured by ELISA and reached a peak of approximately 700 pg/ml at 14 days.
      These preliminary results showed that adenovirus-mediated delivery of the IL-4
      gene may result in a significant inhibition of rat C6 cell tumor growth. Further
      studies will be necessary to refine this anti-tumor effect for as a potential
      therapy for cancer.

PMID- 9584961
TI  - PCR detection of JC virus DNA in the brain tissue of a 9-year-old child with
      pleomorphic xanthoastrocytoma.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare cerebral tumor of young adults with
      a slow growth and a good prognosis. Due to its peculiar histopathological
      findings, the tumor resemble to the lytic phase of progressive multifocal
      leukoencephalopathy (PML), a JC Virus (JCV) induced disease. For these reasons,
      the presence of JCV genoma and viral particles were searched for by means of
      nested polymerase chain reaction (nPCR) and electron microscopy (EM) in a 9-year
      old child with PXA. Although EM did not reveal any viral particles, nPCR did
      reveal genomic sequences of the LT, R, and VP1 regions of JCV. Sequence analysis
      showed that the R region was mutated with respect to the archetypal form thus
      yielding the Mad 4 variant of JCV previously reported as being oncogenic in
      animals. We suggest that JCV may have played a role in the development of this
      tumor.

PMID- 9584962
TI  - A conceptual framework for explaining drug addiction.
AB  - The aim of this paper is to describe a conceptual framework of questions which an
      adequate theory of drug addiction must attempt to answer. First, a satisfactory
      definition of addiction is sought and it is concluded that it is best defined by
      repeated failures to refrain from drug use despite prior resolutions to do so.
      This definition is consistent with views of addiction that see decision-making,
      ambivalence and conflict as central features of the addict's behaviour and
      experience. On this basis, a three-level framework of required explanation is set
      out, consisting of (1) the level of neuroadaptation, (2) the level of desire for
      drugs and (3) the level of 'akrasia'or failures of resolve. The crucial argument
      is made that explanatory concepts used at the'lower' levels in this framework can
      never be held to be sufficient as explanations at higher levels, i.e. the
      postulation of additional determinants is always required at Levels 2 and 3. In
      particular, it is a failure to address problems at the highest level in the
      framework that marks the inadequacy of most existing theories of addiction. The
      paper concludes by considering the relevance of the ideas presented to the
      concept of 'compulsive drug use' and concludes that this concept is no longer
      useful in the explanation of addiction.

PMID- 9584963
TI  - Competing motivations: drug reinforcement vs non-drug reinforcement.
AB  - A behavioral pharmacological conceptualization of drug abuse is summarized, which
      views drug abuse as learned operant behavior that is reinforced by positive
      effects produced by drugs of abuse. In this view drug abuse may be better
      characterized as involving attraction rather than compulsion. Incentive-based
      treatments may be useful for overcoming and competing with the reinforcing
      effects of drugs of abuse. Illustrative examples of incentive-based treatments
      for drug abuse, and their results, are described. The efficacy of incentive-based
      treatments indicates that many substance abusers possess the necessary skills to
      achieve abstinence and suggests that motivational interventions alone may be
      sufficient in many cases. Areas for further research are discussed that relate to
      refining and developing incentive-based therapies and to improving their
      practical utility and public acceptability.

PMID- 9584964
TI  - Conditioning factors in drug abuse: can they explain compulsion?
AB  - There is a good deal of clinical evidence suggesting that compulsion to resume
      drug taking is an important part of the addiction syndrome. The symptoms
      comprising motivation to resume drug use, namely craving and compulsion, have
      been studied experimentally in human subjects. While much work remains to be
      done, there is evidence showing that these symptoms are influenced by learning.
      The research has been guided by animal studies demonstrating that drug effects
      can be conditioned. Much attention has been directed toward demonstrating the
      existence of drug conditioning in human addicts and exploring the neurological
      structures that may underlie such learned responses. We do not yet know the
      relative importance of learning in the overall phenomenon of relapse, and
      treatments based on conditioning principles are still under investigation.

PMID- 9584965
TI  - Is craving the source of compulsive drug use?
AB  - Compulsive drug use, which is typically portrayed as a defining quality of
      addictive behavior, has been described as a pattern of drug consumption that is
      stimulus bound, stereotyped, difficult to regulate and identified by a loss of
      control over intake. It is widely assumed that compulsive drug use is caused by
      drug craving. This assumption is supported by numerous findings of a general
      correspondence between measures of craving and drug-use behavior. A more focussed
      analysis of the available data, however, reveals that craving and drug use are
      not coupled to the degree required by the hypothesis that craving is the source
      of all drug use in the addict. As an alternative to this craving-based view,
      compulsive drug use could be characterized as a form of automatized behavior.
      Automatic performance is assumed to develop over the course of repeated practice
      of motor and cognitive skills. Automatized behavior, like compulsive drug use,
      tends to be stimulus bound, stereotyped, effortless, difficult to control and
      regulated largely outside of awareness. The formulation of drug compulsion as a
      manifestation of automaticity rather than craving allows addiction researchers to
      apply methods and measures derived from cognitive sciences to investigate the
      fundamental organization of compulsive drug-use behavior.

PMID- 9584966
TI  - Integrating the cognitive and physiological aspects of craving.
AB  - 'Craving is generally considered a significant factor in opiate addiction that is
      associated with drug-dependence and in relapse to drug use after treatment'-ARC
      expert consensus (Pickens and Johanson, Drug and Alcohol Dependence 30: 127-131).
      There are however difficulties in defining craving and urges to use drugs and in
      associating craving with drug use and relapse. Tiffany [Psychological Review
      97(2): 147-168] has reviewed a considerable number of studies that associated
      reports of craving with consumption measures of drugs and revealed only an
      overall modest correlation of 0.4. These findings call into question the general
      assumption that subjective cravings are invariably associated with drug use.
      Furthermore, it led to Tiffany's provocative argument that cravings are not
      necessary for drug use. We have addressed these issues by using a range of
      complementary techniques derived from research in related fields such as the
      cognitive psychology of anxiety and depression, physiological response
      measurements and positron emission tomography (PET) neuro-imaging. Initially we
      developed computerized assessments to probe cognitive dysfunction in addiction
      that related to biased processing of automatic thoughts and beliefs about craving
      and drug use in opiate-dependent subjects and alcoholics. Subsequently in an
      attempt to develop a reliable method of inducing craving we explored an imagery
      based technique that relied on the memory of craving experiences. These
      experiments were conducted both in opiate addicts who had achieved abstinence and
      in those undergoing detoxification. Finally, we have begun a study to understand
      the neural mechanisms of craving using imagery-based procedures at the same time
      as performing PET studies of regional blood flow using the O15-labelled water
      technique.

PMID- 9584967
TI  - Substance dependence as a compulsive behavior.
AB  - A compulsion to take a drug combined with a loss of control in limiting intake is
      the defining feature of substance dependence or addiction, and is the conceptual
      framework for the criteria of substance dependence or addiction outlined by the
      World Health Organization and the American Psychiatric Association. However,
      defining exactly what constitutes loss of control and compulsive drug taking at
      the level of animal models is a daunting task, and it is clear that no validated
      animal model exists for the whole syndrome of addiction. The present discussion
      redefines loss of control as a narrowing of the behavioral repertoire toward drug
      seeking behavior and suggests that there are many sources of reinforcement that
      contribute to this behavioral focus on drug seeking. Evidence is presented
      demonstrating separate animal models for many of these sources of reinforcement
      as well as for most of the criteria for substance dependence. Evidence is also
      presented showing that the brain neurochemical systems involved in processing
      drug reward are altered by chronic drug exposure to contribute additional sources
      of reinforcement. Challenges for the future involve not only elucidation of the
      neurobiological substrates of the different behavioral components of addiction,
      but better animal models of these components with which to effect such studies.

PMID- 9584968
TI  - A role for sensitization in craving and relapse in cocaine addiction.
AB  - Sensitization to cocaine refers to the behavioral model of cocaine addiction
      where the motor stimulant effect of cocaine is augmented for months after
      discontinuing a regimen of repeated cocaine injections. There has been
      speculation that the neuroadaptations mediating this sensitization phenomenon
      may, in part, underlie the behavioral changes produced by chronic cocaine abuse,
      including paranoia, craving and relapse. Criteria are proposed that may assist in
      determining which neuroadaptations are most relevant in this regard. Using these
      criteria, a model is presented that endeavors to incorporate neuroadaptations
      issuing directly from the pharmacological effects of cocaine and those arising
      from learned associations the organism makes with the cocaine injection procedure
      and pharmacological actions. It is proposed that the pharmacological
      neuroadaptations predominate in the manifestation of cocaine-induced paranoia,
      while the changes derived from learning may provide more critical underpinnings
      for cocaine craving and relapse.

PMID- 9584969
TI  - A motivational learning hypothesis of the role of mesolimbic dopamine in
      compulsive drug use.
AB  - The effects of drugs and substances of abuse on central dopamine (DA)
      transmission studied by in vivo monitoring techniques have been examined and
      compared with those of conventional reinforcers and in particular with food. The
      similarities and differences in the action of drugs and conventional reinforcers
      on DA transmission can provide the basis for an hypothesis of the mechanism of
      drug addiction and compulsive drug use. This hypothesis states that drug
      addiction is due to excessive control over behaviour exerted by drug-related
      stimuli as a result of abnormal motivational learning induced by repeated drug
      exposure. Such abnormal motivational learning would derive from the repetitive
      non-habituating property of drugs of abuse to activate DA transmission phasically
      in the nucleus accumbens (NAc) 'shell'. Thus, activation of DA transmission by
      conventional reinforcers is under strong inhibitory control by previous exposure
      to the reinforcer (habituation); this, however, is not the case with drug
      reinforcers. Repetitive, non-adaptive release of DA in the NAc 'shell' by drugs
      of abuse would result in abnormal strengthening of stimulus-reward (incentive
      learning) and stimulus-response associations (habit learning) that constitute the
      basis for craving and compulsive drug use.

PMID- 9584970
TI  - 5-hydroxytryptamine and impulse control: prospects for a behavioural analysis.
AB  - Impulsiveness is a significant clinical problem associated with a variety of
      psychiatric and neuropsychiatric disorders. Clinical and experimental studies
      have provided evidence that individuals displaying impulsive behaviour tend to
      show signs of deficient functioning of the ascending 5-hydroxytryptaminergic (5
      HTergic) pathways of the brain. A persistent problem in investigations of the
      biological basis of impulsive behaviour has been the lack of a satisfactory
      definition of 'impulsiveness', as distinct from other behavioural features, such
      as aggression, which are often apparent in 'impulsive' individuals. Research in
      the experimental analysis of behaviour suggests that two important
      characteristics of 'impulsiveness' are (i) deficient tolerance of delay of
      gratification and (ii) inability to inhibit or delay voluntary behaviour; both of
      these characteristics are amenable to study in laboratory animals. We describe
      some delayed reinforcement and delayed response paradigms which purport to
      capture these behavioural characteristics, and review recent evidence that
      manipulation of 5-HTergic function alters behaviour in these paradigms. It is
      argued that the two characteristics of 'impulsiveness' are themselves the product
      of disturbance of more fundamental behavioural processes; the nature of these
      processes is considered.

PMID- 9584971
TI  - Cognitive performance in recreational users of MDMA of 'ecstasy': evidence for
      memory deficits.
AB  - Cognitive task performance was assessed in three groups of young people: 10
      regular users of 3,4-methylenedioxymethamphetamine (MDMA) who had taken 'ecstasy'
      10 times or more; 10 novice MDMA users who had taken 'ecstasy' one to nine times;
      and 10 control subjects who had never taken MDMA. A computerized battery of
      cognitive tasks (Cognitive Drug Research system) was undertaken on a day when
      subjects were drug free. Performance on the response speed and vigilance measures
      (simple reaction time, choice reaction time, number vigilance), was similar
      across the three subgroups. However on immediate word recall and delayed word
      recall, both groups of MDMA users recalled significantly less words than
      controls. Animal research has shown that MDMA can lead to serotonergic
      neurodegeneration, particularly in the hippocampus and frontal cortex. Although
      the design of this study was far from ideal, these data are consistent with other
      findings of memory decrements in recreational MDMA users, possibly caused by
      serotonergic neurotoxicity.

PMID- 9584972
TI  - The stimulus properties of two common over-the-counter drug mixtures:
      dextromethorphan + ephedrine and dextromethorphan + diphenhydramine.
AB  - Two groups of rats were trained in a two-choice drug discrimination procedure
      under a fixed-ratio 10 schedule of food reinforcement. One group of rats (n=12)
      was trained to discriminate the presence and absence of a drug mixture containing
      10 mg/kg dextromethorphan + 10 mg/kg diphenhydramine. The other group of rats
      (n=12) was trained to discriminate the presence and absence of another drug
      mixture containing 10 mg/kg dextromethorphan + 10 mg/kg ephedrine. Cross
      generalization tests conducted with each of the stimulus elements demonstrated
      that (1) the drug mixtures were not perceived as new entities distinct from their
      component elements and (2) the stimulus element saliency may be a factor
      determining the nature of discriminative control by drug mixtures. Cross
      generalization tests conducted with the psychomotor stimulants, cocaine and
      amphetamine, engendered complete generalization to the training cues in both
      groups, whereas, pentobarbital engendered predominantly saline- or default-lever
      responding. These data suggest a potential abuse liability for both of these
      common over-the-counter drug mixtures and cautions against the use of such
      combinations in pediatric patients.

PMID- 9584973
TI  - A naturalistic study of home detoxification from opiates using lofexidine.
AB  - The study describes the outcome of home detoxification from opiates using
      lofexidine, a centrally-acting alpha2-adrenergic agonist, in a consecutive series
      of 28 unselected individuals. Eleven detoxifications (39%) were successful and 17
      (61%) unsuccessful. No major medical or psychological problems were reported.
      Successful outcome was associated with not using heroin, good compliance with a
      methadone programme and prediction of success by the key worker. Home
      detoxification using lofexidine appears to be a useful treatment for some opiate
      dependent individuals, and is most likely to be successful in those individuals
      whose drug use is already well-controlled.

PMID- 9584974
TI  - The psychobiology of MDMA or 'ecstasy': symposium arranged by the Psychobiology
      Section, at the Annual Conference of the British Psychological Society, Heriot
      Watt University, Edinburgh, April 1997.

PMID- 9584975
TI  - Zolpidem tolerance and dependence--two case reports.
AB  - Two cases of zolpidem tolerance and dependence are reported. The literature is
      reviewed for other reported cases, and the potential for abuse of zolpidem is
      discussed.

PMID- 9584977
TI  - Self-medication with alcohol appears not to be an effective treatment for the
      control of depression.

PMID- 9584976
TI  - Pindolol augmentation of sertraline in resistant depression and its effect on
      sleep.
AB  - A case is reported of a 34-year-old lady with a 2-year history of resistant
      depression who responded to pindolol augmentation of sertraline. It also
      illustrates the use of sleep electroencephalogram measures as a way of assessing
      changes in brain 5-hydroxytryptamine function.

PMID- 9584978
TI  - Responses of intestinal and renal alpha-glycosidases to alloxan and
      streptozotocin-induced diabetes: a comparative study.
AB  - Experimentally induced diabetes in the rat resulted in an increased level of
      alpha-glycosidases in the intestine but a depression in their levels in the
      kidney. Rat intestine exhibited a differential stimulation of maltase, sucrase
      and trehalase activities. The variations depended on the duration of diabetes and
      the beta-cytotoxic compounds used i.e. alloxan and streptozotocin. The maximum
      elevation in terms of total units and specific activity was observed on the 30th
      day in the following order: maltase>sucrase>trehalase. A significant observation
      emerging from this study is that the level of intestinal enzymes increases while
      that of the kidney enzymes declined during the period. Although intestinal and
      renal alpha-glycosidases are known to be structurally and biochemically similar,
      their opposing responses to diabetes indicates that they are under different
      regulatory mechanisms in these tissues.

PMID- 9584979
TI  - Establishment of a mouse clonal early proximal tubule cell line and outer
      medullary collecting duct cells expressing P2 purinoceptors.
AB  - The purpose of this study was to establish tubule cells expressing P2
      purinoceptors. Use of the polymerase chain reaction coupled with reverse
      transcription showed that mouse clonal early proximal tubule (S1) cell line (NF
      5) and outer medullary collecting tubule (OMCT) cells expressed mRNA for P2X4,
      P2Y1 and P2Y2 purinoceptors. ATP and its analogues induced a dose-dependent
      increase in cytosolic free calcium concentration ([Ca2+]i) in both NF-5 and OMCT
      cells. ATP enhanced [3H]-thymidine uptake by both NF-5 and OMCT cells in a dose
      dependent manner. In conclusion, NF-5 and OMCT cells can be used in the further
      analysis of the function and regulation of activity and expression of P2
      purinoceptors in the renal tubule.

PMID- 9584980
TI  - The effect of ribosome-inactivating proteins on the ribosome from the
      hyperthermophilic archaeon Sulfolobus solfataricus.
AB  - Protein synthesis in the thermoacidophilic archaeon Sulfolobus solfataricus (Ss)
      was inhibited by polynucleotide:adenosine glycosylase activity of some type 1
      ribosome-inactivating proteins (RIP). The target of RIP was S. solfataricus rRNA
      that was depurinated thus producing inactive ribosomes. The amount of RIP
      required to half-inactivated Ss-ribosomes was comparable to that needed for
      eubacterial ribosomes, but two orders of magnitude higher than that required for
      mammalian ribosomes. In addition, RIP treated Ss-ribosomes were also less
      efficient in stimulating the ribosome dependent GTPase activity of the S.
      solfataricus elongation factor 2 (SsEF-2) thus suggesting that the inhibition of
      protein synthesis was probably due to the lack of the interaction between
      depurinated Ss-ribosomes and SsEF-2. Since SsEF-2 protects Ss-ribosomes against
      RIP activity it can be hypothesised that also on Ss-ribosomes the sites of
      interaction for the translocation factor 2 and the RIP are topographically close.

PMID- 9584981
TI  - Molecular cloning of a novel chemokine receptor-like gene from early stage chick
      embryos.
AB  - Proliferation, differentiation and regulated trafficking of cells are the
      hallmarks of development and embryogenesis. This led us to speculate a role for
      chemokines and their receptors in this process. Here, we report the molecular
      cloning of AvCRL1, a novel member of the G-protein coupled receptor family from
      early stage 3 days old chick embryos. While the function and ligand for this
      receptor remain unknown, its sequence and gene structure indicates that it is
      most related to the family of chemokine receptors, with highest homology to the
      virally induced human BLR-1 and the CXCR3 or gammaIP-10/Mig-1 receptors.

PMID- 9584982
TI  - Identification of an enhancer sequence in 5'-flanking region of 1A exon of mouse
      liver/bone/kidney-type alkaline phosphatase gene.
AB  - The 5'-flanking region of the 1A exon of the mouse liver/bone/kidney-type
      alkaline phosphatase (L/B/K ALP) gene was analyzed for the promoter activity.
      Luciferase assays revealed that a segment containing a 9 bp inverted repeat (nt 
      1212 to -1179, designated as IRS for inverted repeat segment) had an enhancer
      activity. Though an E-box at nt -234 did not have a prominent promoter activity,
      the effect of IRS required its presence. Both transcriptional activity and IRS
      binding to the nuclear proteins were similarly observed even in cells that did
      not express ALP. Bone morphogenetic protein-2 (BMP-2) induced the ALP expression
      in pluripotent C3H10T1/2 cells, but it did not increase the transcriptional
      activity of the promoter region. Though they do not determine cell specific or
      BMP-2 inducible ALP expression, IRS and the E-box at position -241 seem to be
      important for the basic transcriptional activity of ALP gene.

PMID- 9584983
TI  - Hepatic heterogeneity in the response to AMP studies in the bivascularly perfused
      rat liver.
AB  - The zonation of the purinergic action of AMP in the hepatic parenchyma was
      investigated in the bivascularly perfused rat liver by means of anterograde and
      retrograde perfusion. Livers from fed rats were used and AMP (100 microM) was
      infused according to four different experimental protocols: (A) anterograde
      perfusion and AMP infusion via the portal vein; (B) anterograde perfusion and AMP
      infusion via the hepatic artery; (C) retrograde perfusion and AMP via the hepatic
      vein; (D) retrograde perfusion and AMP via the hepatic artery. The response of
      the liver cells was heterogeneous. Oxygen uptake inhibition by AMP predominates
      in cells situated shortly after the intrasinusoidal confluence of the portal vein
      and hepatic artery. Oxygen consumption in all other cells seems to be increased
      by AMP. Glycogenolysis stimulation by AMP (glucose release) was more pronounced
      in the periportal cells situated in the region of the intrasinusoidal confluence
      of the portal vein and the hepatic artery. It can be concluded that the
      heterogenic response of the liver to AMP is similar to the heterogenic response
      to ATP.

PMID- 9584984
TI  - PP7, a plant phosphatase representing a novel evolutionary branch of eukaryotic
      protein Ser/Thr phosphatases.
AB  - We describe a novel protein Ser/Thr phosphatase from Arabidopsis thaliana, PP7,
      which is only 27-32% identical in amino acid sequence to the known phosphatases
      and is the most divergent member of the PPP (PP1/2A/2B) family for today. Some
      structural features suggest more close relationship of PP7 to the PP5/rdgC
      subfamily. PP7 contains all of the residues essential for the phosphatase
      activity and possesses three major insertions in its presumable C-terminal
      subdomain, which suggest its unique regulation and/or optimisation of its
      structure for interaction with specific substrates or regulators. A phosphatase
      structurally related to PP7 is expressed in rice. PP7 conservation between mono-
      and dicotyledonous plants may point to its essential role in the plant cell.

PMID- 9584985
TI  - Ascorbate peroxidase and catalase cooperate for protection against hydrogen
      peroxide generated in potato tubers during low-temperature storage.
AB  - We investigated the behavior of the antioxidant enzymes, superoxide dismutase
      (SOD), catalase (CAT), and ascorbate peroxidase (APx), in potato tubers during
      storage at low temperature. SOD activity increased temporarily within 3 weeks and
      was higher at 1 degree C than at 20 degrees C. APx activity also increased more
      at low (1 degree C) than at higher temperatures (5 and 20 degrees C). The
      contents of ascorbic acid (AsA), which is the substrate of APx, decreased
      immediately within 3 weeks and then gradually decreased until 15 weeks. The
      activity of CAT, the other enzyme which can scavenge hydrogen peroxide, decreased
      once in the first six weeks and thereafter increased to 15 weeks. Thus, the
      enhancement of the active oxygen-scavenging system that was induced by low
      temperature in potato tubers could result not only in a decrease of AsA but also
      in combined increases in APx and CAT activity whose manners were different.

PMID- 9584986
TI  - The effects of lifelong ubiquinone Q10 supplementation on the Q9 and Q10 tissue
      concentrations and life span of male rats and mice.
AB  - The effect of lifelong oral supplementation with ubiquinone Q10 (10 mg/kg/day)
      was examined in Sprague-Dawley rats and C57/B17 mice. There were no significant
      differences in survival or life-span found in either rats or mice.
      Histopathologic examination of different rat tissues showed no differences
      between the groups. In Q10 supplemented rats, plasma and liver Q10 levels were
      2.6 to 8.4 times higher at all age points than in control rats. Interestingly, in
      supplemented rats the Q9 levels also were significantly higher (p<0.05) in plasma
      and liver at ages 18 and 24 months. Neither Q9 nor Q10 levels were affected by
      supplementation in kidney, heart, or brain tissues. In spite of the significant
      changes in plasma and liver ubiquinone concentrations, lifelong Q10
      supplementation did not prolong or shorten the lifespan of either rats or mice.

PMID- 9584987
TI  - Effect of salts on the interaction of oxidized glutathione with dibasic amino
      acids.
AB  - The interaction of oxidized glutathione (GSSG) with dibasic amino acids was
      studied with charge-transfer chromatography carried out on unimpregnated
      cellulose layers in the absence and presence of LiCl, NaCl, KCl, MgCl2 and CaCl2.
      GSSG decreased in each case the apparent lipophilicity of dibasic amino acids,
      indicating some type of interaction. Calculations proved that the strength of
      GSSG - dibasic amino acid interaction decreases with increasing concentration of
      salts suggesting a hydrophilic character of interaction. It can be assumed that
      electrostatic forces between the carboxyl group of GSSG and the amino groups of
      amino acids are involved in the interaction. GSSG binds stronger to arginine than
      to lysine and ornithine suggesting that arginine is probably the primary binding
      site in proteins for GSSG.

PMID- 9584988
TI  - Menadione toxicity in Saccharomyces cerevisiae cells: activation by conjugation
      with glutathione.
AB  - Menadione (2-methyl-1,4-naphthoquinone) has been used extensively as an oxidant
      stressor at the cellular level. However, the mechanism of cytotoxicity of this
      compound still remains controversial. This study deals with the role of
      intracellular glutathione in the resistance of the yeast Saccharomyces cerevisiae
      to menadione. Incubation with 0.5 mM menadione resulted in a decrease of total
      glutathione concentration in yeast cells, intracellular formation of menadione S
      glutathione conjugate and export of the conjugate from cells. GSH-deficient
      mutants showed lower stimulation of superoxide and hydrogen peroxide production
      upon exposure to menadione and were more resistant to menadione than wild-type
      isogenic strains. These results indicate that in yeast cells the formation of S
      glutathione conjugate is a major pathway of menadione metabolism and that this
      reaction leads to redox activation of menadione but permits its removal from the
      cells.

PMID- 9584989
TI  - Structural characterization of human glyoxalase II as probed by limited
      proteolysis.
AB  - Human glyoxalase II is partially proteolyzed by trypsin, under non denaturing
      conditions, only at the level of the C-terminal region. The proteolytic cleavage
      resulted in an inactivation of the enzyme without loss of the secondary
      structure. Sodium dodecyl sulphate polyacrylamide gel-electrophoresis and
      microsequence analysis showed that the glyoxalase II is proteolyzed at the level
      of Arg 184 and Lys 230 and undergoes a third cleavage in a region located at the
      beginning of the supposed C-terminal domain. The proteolysis occurs either in the
      presence or in the absence of specific inhibitors. Our limited proteolysis
      experiments and secondary structure prediction give evidence for the presence of
      two domains characterized by different pattern of secondary structure.

PMID- 9584990
TI  - Effect of lipids on the conformation of an antigenic determinant for experimental
      autoimmune neuritis.
AB  - The conformation of SP-26, the synthetic peptide (residues 53-78) of myelin P2
      protein that causes experimental autoimmune neuritis (EAN) in the peripheral
      nervous system, has been studied in lipid environments and in
      water/trifluoroethanol (TFE) mixture using circular dichroism (CD) spectroscopy
      and Fourier transform infra-red (FTIR) spectroscopy. SP-26 becomes more
      structured on binding with micelles formed from anionic lipids and in the
      presence of TFE. On the other hand, zwitterionic lipids have a denaturing effect
      or no effect on the conformation of SP-26. The present results suggest that the
      disease-modulating effects of various lipids are closely related to their ability
      to induce conformational change in the antigenic region of P2 protein.

PMID- 9584991
TI  - Partial characterization of the lipopolysaccharides of peanut specific
      Bradyrhizobium strains.
AB  - Hexoses, heptose, hexuronic acids, 2-keto-3-deoxyoctonic acid (Kdo) contents of
      the lipopolysaccharides (LPS) isolated from peanut (A. hypogaea) specific
      Bradyrhizobium strains NC 92, IGR 92, IGR 40 and IGR 6 were found to vary
      considerably. Sodium dodecyl sulphate polyacrylamide gel electrophoresis showed a
      heterogeneous LPS population and distinct heterogeneity was observed in NC and
      IGR strains. Sepharose gel filtration chromatography removed the hexose
      contaminants from NC 92 LPS. Polysaccharides obtained by mild acid hydrolysis of
      Sepharose purified NC 92 LPS were further purified on Sephadex G-50 gel
      filtration. Immunoblot analysis indicated cross reactivity amongst the peanut
      specific Bradyrhizohium strains but not with B. japonicum(SB 16). Antibodies
      raised against native NC 92 LPS showed higher binding towards the Sephadex
      purified polysaccharides suggesting the antigenic property of polysaccharide
      moiety in LPS molecule.

PMID- 9584992
TI  - Spirulina maxima prevents induction of fatty liver by carbon tetrachloride in the
      rat.
AB  - The aim of the present work was to assess the capacity of Spirulina maxima to
      prevent fatty liver development induced in rats by an intraperitoneal single dose
      (1 ml/kg) of carbon tetrachloride. Liver and serum lipids were quantified two or
      four days after treatment with this agent. Liver lipid concentration did not
      differ in rats fed on a purified diet with or without Spirulina. However, after
      carbon tetrachloride treatment, liver triacylglycerols were significantly lower
      in rats fed on a diet with Spirulina 5% than in rats without Spirulina in their
      diet (P < 0.05). Furthermore, the increased liver cholesterol values, induced by
      carbon tetrachloride treatment, were not observed in rats that received
      Spirulina. These results support the potential hepatoprotective role of
      Spirulina.

PMID- 9584993
TI  - Subunit structure of lysine sensitive aspartate kinase from spinach leaves.
AB  - The lysine-sensitive isoenzyme of aspartate kinase was purified to homogeneity
      from spinach leaves and its subunit composition was studied. The purified
      preparation had an apparent molecular mass of 280,000 and separated into two
      subunits- a large subunit with molecular mass of 53,000 and smaller subunit with
      molecular mass of 17,000 by urea treatment and SDS PAGE. The enzyme molecule has
      subunit composition of 4 large and 4 small subunits. The activity of the large
      subunit was stimulated more than two fold by the addition of small subunit and
      the stimulated activity was inhibited by EGTA. This inhibition could be reversed
      by Ca++. Further characteristics of the smaller subunit such as heat stability,
      behavior on ion exchange chromatography, elctrophoretic mobility on
      polyacrylamide gels, amino acid composition and pattern, presence of trimethyl
      lysine, its ability to activate other calmodulin stimulated enzymes and its
      calmodulin-like nature in RIA tests suggested that this subunit is identical to
      calmodulin.

PMID- 9584994
TI  - Role of naturally occurring autoantibodies in senescence of normal and ATP
      depleted goat erythrocytes.
AB  - The possible role of autoantibodies in the senescence of goat erythrocytes has
      been investigated. For this purpose goat gammaglobulin was purified to
      homogeneity and antigoat gammaglobulin was raised in rabbits. Using the
      peroxidase labelled antigoat gammaglobulin it was possible to detect the presence
      of auto anti band-3 antibodies in goat sera. The goat erythrocytes were aged in
      vitro by ATP-depletion, which resulted in appearance of a 52,000 mol. wt.
      polypeptide. The in vitro aged goat erythrocyte membrane bound substantial
      amounts of auto anti band-3 antibodies as visualized by immunoblots.

PMID- 9584995
TI  - Response to platelet-derived growth factor by phenotypically different cultured
      human aortic smooth muscle cells.
AB  - We investigated the effects of PDGF on DNA synthesis and mitogen-activated
      protein (MAP) kinase activity, and demonstrated that the adult intimal SMC was
      concentration-dependently stimulated by all PDGF isoforms in terms of both
      [3H]thymidine incorporation and MAP kinase activation, with PDGF-BB and -AB being
      more potent than PDGF-AA. The intimal SMCs and the neonatal SMCs showed a similar
      response with regard to MAP kinase activation. On the other hand, the intimal
      SMCs expressed many more PDGF receptors than the adult medial SMCs, which
      expressed a greater amount of PDGF-A chain mRNA and showed a lesser response to
      PDGFs. These results suggest that the intimal SMCs have a relatively high
      potential to react to exogenous PDGFs, whereas the adult medial SMCs depend on
      endogenous or autocrine secretion of PDGF-AA.

PMID- 9584996
TI  - Effects on larvicidal activity of single proline substitutions in alpha3 or
      alpha4 of the Bacillus thuringiensis Cry4B toxin.
AB  - The possible role of alpha-helices 3 and 4 in toxicity of the dipteran-active
      Bacillus thuringiensis Cry4B delta-endotoxin was investigated by employing
      proline substitutions via site-directed mutagenesis. Similar to the wild-type
      Cry4B, the mutant toxins were over-expressed in Escherichia coli as cytoplasmic
      inclusions and were structurally stable upon solubilization and trypsin
      activation. The substitution of glutamine 149 by proline in the center of helix 4
      (Q149P) resulted in a nearly complete loss of toxicity against Aedes aegypti
      mosquito-larvae. However, single proline replacements near the center of helix 3
      (V119P) and at the N-terminus of helix 4 (Q140P) did not decrease larvicidal
      activity. The toxicity of E. coli cells expressing the wild-type toxin was
      significantly reduced by two-hour preincubation with the non-toxic mutant
      (Q149P), thus indicating that the primary binding step was not affected by the
      proline substitution in helix 4. The results therefore reveal a crucial role for
      helix 4 of the Cry4B toxin in toxicity, possibly in membrane insertion and pore
      formation rather than in receptor recognition.

PMID- 9584997
TI  - Fatty acid-mediated uncoupling of potato tuber mitochondria.
AB  - The present work examined whether the ATP/ADP carrier, other than the plant
      uncoupling mitochondrial protein, participates in free fatty acid-mediated
      uncoupling of potato tuber mitochondria. The basal respiration rate of succinate
      energized mitochondria was stimulated by a low concentration of palmitate (20
      microM). This uncoupling was reversed by 10 microM carboxyatractyloside and by
      the subsequent addition of 0.1% bovine serum albumin. The decrease in membrane
      potential caused by palmitate was suppressed by carboxyatractyloside (1 microM)
      and, to a lesser degree, by bongkrekate (20 microM). GTP could also reversed this
      decrease via a carboxyatractyloside-independent mechanism. These results indicate
      that the ATP/ADP carrier, along with the plant uncoupling mitochondrial protein,
      participates in the protonophoric action of palmitate in potato tuber
      mitochondria.

PMID- 9584998
TI  - Purification and characterization of CD38/ADP-ribosyl cyclase from rat lung.
AB  - Purification and characterization of CD38/ADP-ribosyl cyclase in the rat lung
      tissue was performed with microsomes solubilized in Triton X-100 and the ADP
      ribosyl cyclase was then purified using sequential column chromatography.
      Partially purified rat lung ADP-ribosyl cyclase was analyzed by immunoblotting
      using an antibody raised against a recombinant rat CD38 and showed the presence
      of monomer (42 kDa) and dimer (85 kDa) under non-reducing conditions but under
      reducing conditions, only the monomer was detected. Both the monomer and dimer
      could be eluted out in a stable manner from SDS-PAGE and the enzymatic activity
      was retained by the two different forms of CD38/ADP-ribosyl cyclase.
      Immunohistochemical staining showed the presence of CD38 on the bronchial
      epithelium and the alveoli.

PMID- 9584999
TI  - Involvement of available SH groups in the heterogeneity of hemoglobin from the
      tortoise Geochelone carbonaria.
AB  - Geochelone carbonaria hemoglobin (Hb) was analyzed by polyacrylamide gel
      electrophoresis (PAGE) and purified by ion exchange chromatography on CM
      cellulose. Seven fractions were obtained using fresh Hb preparations. CM
      cellulose chromatography of Hb reacted with iodoacetamide, showed one minor (HbI)
      and one major band (HbII). Analysis of the molecular masses of recently collected
      Hb and of aged solutions determined by gel filtration showed that polymerization
      increased with the duration of storage. The reaction with oxidized glutathione
      changed the electrophoretic pattern of Hb, and highlighted the bands
      corresponding to glutathionyl-Hb. The presence of these bands in fresh Hb
      solutions and in alkylated preparations suggests that they may occur in vivo.
      PAGE under dissociating conditions showed that the hemolysate contained 3
      different polypeptide chains (G1, G2 and G3). Both Hb components shared the G1
      globin chain with HbI containing G1 and G2 and HbII, G1 and G3 chains.

PMID- 9585000
TI  - Intrauterine growth retardation alters mitochondrial gene expression and function
      in fetal and juvenile rat skeletal muscle.
AB  - Uteroplacental insufficiency alters the anabolic metabolism of the fetus,
      resulting in intrauterine growth retardation (IUGR). The metabolic and
      physiologic factors that cause IUGR have long standing consequences after birth.
      Postnatal growth and glucose metabolism are altered in the IUGR infant. Skeletal
      muscle is an important component of growth and metabolizes up to 70% of i.v.
      glucose. The ability of skeletal muscle to metabolize glucose is affected by ATP
      availability. We hypothesized that gene expression and function of proteins
      involved in mitochondrial ATP production and distribution would be altered in
      juvenile IUGR muscle. To test this hypothesis, we used a model of IUGR, induced
      by bilateral uterine artery ligation in the pregnant rat, that mimics
      uteroplacental insufficiency in the human. RT-PCR was used to measure the mRNA
      levels of three important mitochondrial proteins; NADH-ubiquinone-oxireductase
      subunit 4L(ND-4L), subunit C of the F1F0-ATP synthase (SUC), and adenine
      nucleotide translocator 1 (ANT1) in IUGR and control rats in fetal and juvenile
      life. In the fetus, mRNA levels of all three proteins were significantly
      increased in IUGR skeletal muscle. In contrast, in juvenile animals, mRNA levels
      of all three proteins were significantly decreased. mRNA levels of other
      metabolically important proteins, glucose-6-phosphate dehydrogenase and carnitine
      palmitoyl-transferase II, were not significantly altered in IUGR juvenile
      animals. To assess if decreased gene expression is associated with altered
      mitochondrial function, we measured the mitochondrial NAD+/NADH ratio in d 21
      juvenile control and IUGR muscle. At d 21, decreased gene expression if ND-4L,
      SUC, and ANTI is associated with a decreased mitochondrial NAD+/NADH ratio. The
      results of our study suggest that the metabolic alterations associated with
      uteroplacental insufficiency in the rat result in altered fetal and postnatal
      muscle mitochondrial mRNA expression as well as altered postnatal mitochondrial
      function.

PMID- 9585001
TI  - Genotypic heterogeneity and phenotypic variation among patients with type 2
      Gaucher's disease.
AB  - Gaucher's disease, the inherited deficiency of glucocerebrosidase, manifests with
      vast phenotypic variation. Even among patients with type 2 (acute neuronopathic)
      Gaucher's disease, there is a spectrum of clinical presentations. DNA samples
      from 14 patients with type 2 Gaucher's disease with a course ranging from
      intrauterine death at 22 wk of gestation to survival until age 30 mo were
      studied. L444P was the only common mutation identified, found in 15 patients'
      alleles. Sequencing of genomic DNA amplified by long template PCR revealed that
      mutation L444P occurred as a single point mutation in seven mutant alleles and as
      part of a recombinant allele in eight mutant alleles. Two patients had a deletion
      of 55 bp in exon 9; in one patient the deletion was part of a recombinant allele,
      and in a second the deletion occurred alone. Direct sequencing identified R120W
      on one allele, P415R on another, and one fetus was homoallelic for a deletion of
      a C nucleotide at codon 139 in exon 5. Eight of the mutant alleles remain
      unidentified. Northern blots revealed an appropriately sized mRNA in all except
      one of the patients studied. Of the 14 type 2 Gaucher patients, three had hydrops
      fetalis and died in utero or at birth, five had congenital ichthyosis, and seven
      survived 5 mo or more. Patients who died in the neonatal period had decreased
      protein detected by Western blot, regardless of genotype observed. These studies
      demonstrate that genotypic heterogeneity exists in patients with type 2 Gaucher's
      disease, even among infants with the most severe phenotypes.

PMID- 9585002
TI  - Molecular characterization of pyruvate carboxylase deficiency in two
      consanguineous families.
AB  - Pyruvate carboxylase (PC) is a biotinylated mitochondrial enzyme that catalyzes
      the conversion of pyruvate to oxaloacetate. Children with inborn errors of PC
      metabolism have lactic acidosis, hypoglycemia, and mental retardation. The
      variable severity of the clinical phenotype is dependent on both genetic and
      environmental factors. Two consanguineous families with moderate forms of PC
      deficiency were characterized at the biochemical and molecular levels. In both
      families, the probands were found to have low PC activity (range, 2-25% of
      control) in blood lymphocytes and skin fibroblasts associated with either
      diminished or normal protein levels. In the first case, sequencing of patient
      specific PC cDNA demonstrated a T to C substitution at nucleotide 434, which
      causes a valine to alanine change at amino acid residue 145. Direct sequencing of
      the parents showed that they are heterozygous for this mutation. In the second
      family, a brother and sister had mental retardation and episodes of severe
      lactic/ketoacidosis in early childhood. In these cases, a C to T substitution at
      nucleotide 1351 results in a cysteine for arginine substitution at amino acid
      residue 451; the parents were also found to be heterozygous for this mutation. In
      both families, no other mutations were found, and both substitutions occurred in
      relatively conserved amino acid residues. These mutations, located in the biotin
      carboxylase domain, provide a unique opportunity to analyze how natural occurring
      mutations affect PC function.

PMID- 9585003
TI  - Premature stimulation of rat sucrase-isomaltase (SI) by exogenous insulin and the
      analog B-Asp10 is regulated by a receptor-mediated signal triggering SI gene
      transcription.
AB  - The mechanism(s) by which insulin enhance prematurely the activity of brush
      border membrane (BBM) hydrolases in rat immature intestine is unknown. Therefore,
      we have compared the responses of four BBM enzymes [sucrase-isomaltase (SI),
      maltase, lactase-phloridzine hydrolase (LPH), and aminopeptidase] with exogenous
      insulin, the analog B-Asp10, IGF-I, and antireceptor MAb [insulin-receptor (IR)
      MAb] given to preweaning pups. Low doses of insulin caused a precocious induction
      of SI and of SI mRNA and stimulated maltase activity without effect on LPH nor on
      aminopeptidase activities. IGF-I given at the same dose as that of insulin had no
      detectable effect on these enzymes. Administration to sucklings of IR MAb
      prevented the effect of endogenous insulin by inhibiting the expression of SI and
      maltase without effect on LPH activity. B-Asp10, an insulin analogue that
      exhibits in vitro a 3.5-fold increase in receptor affinity with sustained
      signaling of the receptor tyrosine kinase, caused an overexpression of SI by 3.5
      fold and of maltase by 1.5-fold compared with equivalent doses of normal insulin.
      The premature increases in SI activity, SI mRNA, and maltase activity in response
      to insulin were dose-dependent and were associated with dose-dependent increases
      in intracellular spermine and spermidine concentrations. In conclusion, these
      data suggest that the premature induction of SI by insulin is mediated by a dose
      dependent signal initiated by binding of the hormone to its intestinal receptor,
      which after transduction into the cell indirectly triggers the transcription of
      the SI gene, possibly by changes in intracellular polyamine concentrations.

PMID- 9585004
TI  - Assessment of whole body L-leucine oxidation by noninvasive L-[1-13C]leucine
      breath tests: a reappraisal in patients with maple syrup urine disease, obligate
      heterozygotes, and healthy subjects.
AB  - Suitability of a recently proposed noninvasive L-[13C]leucine breath test for
      assessment of whole body leucine oxidation in maple syrup urine disease (MSUD)
      was examined. Oral L-[1-13C]leucine loads (38 micromol/kg body weight) were
      performed in overnight fasted MSUD patients (n = 6, classical form), obligate
      heterozygote parents (n = 6), and control subjects (n = 10). Three-hour 13CO2
      exhalation kinetics were evaluated using curve fitting procedures. Venous blood
      was obtained in most cases and analyzed for 13C-labeled plasma metabolites. In
      control subjects, maximal 13CO2 exhalation was reached at tmax = 55 +/- 18 min.
      Cumulative 13CO2 output at 3 h amounted to 4.7 +/- 0.7 micromol x (kg body
      weight)(-1). Estimated total 3CO2 exhalation was 7.2 +/- 1.4 micromol x (kg body
      weight)(-1) (19.0 +/- 3.6% of the dose). Half of this amount was expired at t1/2
      = 130 +/- 18 min. The data show a considerable degree of intersubject
      variability. Intraindividual variability was comparable, however, when checked in
      two volunteers. In obligate heterozygotes, 13CO2 kinetics were similar to
      controls (tmax = 35 +/- 8 min, t1/2 = 95 +/- 16 min). Total 13CO2 output [5.7 +/-
      1.4 micromol x (kg body weight)(-1)] tended to be in the lower control range.
      None of the MSUD patients under study exhibited a significant increase in 13CO2
      output after load. Maximal increase of label in plasma 4-methyl-2-oxopentanoate,
      the physiologic precursor of 13CO2, was 16.1 +/- 3.5 MPE in control subjects. In
      MSUD, label dilution was increased and correlated with the patients' leucine/4
      methyl-2-oxopentanoate plasma levels. Considering the generally high variability
      of 13CO2 output and the unstable substrate pools in MSUD, we discuss the
      limitations of whole body leucine oxidation measurements by noninvasive
      approaches.

PMID- 9585005
TI  - Paradoxical role of ascorbic acid and riboflavin in solutions of total parenteral
      nutrition: implication in photoinduced peroxide generation.
AB  - In the presence of light, a multivitamin preparation is the main source of
      peroxides in solutions of total parenteral nutrition (TPN). This preparation
      contains two photosensitive products, 5'-phosphate flavin mononucleotide (FMN)
      and polysorbates (PS), as well as electron donors such as ascorbate (AH). We
      hypothesized that the admixture of FMN or PS with electron donors generates
      peroxides in TPN and alters the quality of nutrients. Using xylenol orange,
      peroxide concentrations were measured in solutions containing AH, FMN, and/or PS
      in water, a dextrose solution, an amino acid preparation, and a lipid emulsion.
      Thiol functions were evaluated by reduction of 5,5-dithiobis(2-nitrobenzoic acid)
      in the amino acid preparation. After 24-h light exposure, dextrose solutions with
      admixtures of AH + FMN or AH + FMN + PS generated peroxides at concentrations
      similar to those observed in a 1% multivitamin solution, and over three times
      higher than those observed with FMN, PS, or AH alone. However, in the presence of
      amino acids, FMN alone induced a generation of peroxides comparable to that
      observed with FMN + AH. In the lipid emulsion, peroxides increased over 3-fold in
      the presence of FMN or FMN + AH. The addition of catalase suggested that lipid
      peroxides and H2O2 were produced, and the loss of thiol function suggested that
      an oxidation of amino acids occurred. When exposed to light, FMN induces
      reactions with amino acids, polyunsaturated fatty acids, and even AH, altering
      the quality of nutrients. Paradoxically, AH without FMN has a protective effect
      on peroxide generation in TPN.

PMID- 9585006
TI  - Daily energy expenditure and physical activity in survivors of childhood
      malignancy.
AB  - Changes in body composition, in particular the onset of obesity, may result from
      reductions in total daily energy expenditure (TDEE) as a consequence of relative
      physical inactivity. Children previously treated for acute lymphoblastic leukemia
      (ALL) become obese, yet the mechanism remains undefined. TDEE and physical
      activity levels [PAL = TDEE/basal metabolic rate (BMR)] were measured in 34 long
      term survivors of ALL and compared with results from 21 survivors of other
      malignancies and 32 healthy sibling control subjects using the flex-heart rate
      technique. Body composition was measured by dual energy x-ray absorptiometry. The
      median TDEE was reduced in the ALL group (150 kJ x kg d(-1)) compared with other
      malignancies and controls (207 and 185 kJ x kg d(-1), respectively, p < 0.01).
      This reduction was accounted for mainly by a relative decrease in the PAL of the
      ALL group (1.24) compared with both other malignancies and controls (1.58 and
      1.47, respectively, p < 0.01). TDEE and PAL were correlated with percentage body
      fat (r = -0.39, p < 0.001 and r = -0.24, p < 0.05, respectively). Obesity in
      survivors of ALL may, in part, be explained by a reduction in TDEE as a
      consequence of reduced PAL. The cause of such reduction is uncertain.

PMID- 9585007
TI  - Cellular localization of insulin-like growth factor II mRNA in the human fetus
      and the placenta: detection with a digoxigenin-labeled cRNA probe and
      immunocytochemistry.
AB  - IGF-II plays a major role in the regulation of human fetal growth and
      development. However, more extensive information on the cellular sites of IGF-II
      synthesis in the fetus would provide more insight into its role in fetal
      organogenesis. Thus we have determined the sites of IGF-II synthesis in 18-26-wk
      gestation human fetal tissues using in situ hybridization with a digoxigenin
      labeled cRNA probe to localize IGF-II mRNA in fetal liver, kidney, adrenal gland,
      cerebral cortex, costal cartilage, skeletal muscle, and lung, and in placental
      tissue. In human fetal tissues it has to date been impossible to clearly assign
      IGF-II mRNA to epithelial cells of entodermal origin. Besides their already known
      localization in cell matrix and a variety of mesodermal cell types, strong IGF-II
      mRNA-positive signals were detected in epithelial cells in the liver
      (hepatocytes), bronchial and bronchiolar epithelium, undifferentiated renal
      tubular epithelium, mature glomerular epithelium, pelvic urothelium, and adrenal
      epithelial cells of the zona persistens. To identify the cellular location of
      immunoreactive IGF-II, we also performed immunocytochemical studies in tissues of
      the same fetuses. Every tissue studied except the cerebral cortex contained
      immunoreactive cells; however, immunostaining was generally weaker than in situ
      hybridization signals. Our data show that the distribution of IGF-II in human
      fetal tissue is much more widespread than hitherto thought. A digoxigenin-labeled
      detection system for IGF-II is more capable of detecting the cellular expression
      pattern of IGF-II than radioactive probes and is suitable for analysis of
      routinely prepared paraffin-embedded material.

PMID- 9585008
TI  - Permeability of human placenta and fetal membranes to thyrotropin-stimulating
      hormone in vitro.
AB  - We determined the placental transfer of TSH in an in vitro model of dually
      perfused isolated lobule in 28 human term placentas by adding varying
      concentrations (5-60 microIU mL(-1)) of TSH as a single bolus dose to the closed
      maternal circulation. Transmembrane transfer of TSH was also studied by adding 45
      microIU mL(-1) to the maternal or fetal compartment of a dual chamber of fetal
      membranes in culture. Passage of freely diffusible markers creatinine and
      antipyrine were also studied in this model. TSH concentration was measured by
      third generation chemiluminescence assay with a sensitivity of 10 mIU mL(-1). In
      the perfusion experiments, at physiologic concentrations the slow decline of TSH
      in the maternal circulation was associated with a small linear increase in fetal
      levels to 0.11 +/- 0.04% of initial dose at 2 h. The placental transfer rate was
      0.08 microIU min(-1). Increasing maternal concentrations of TSH were associated
      with proportional increases in transfer rate (y = 0.002x; R2 = 0.99) and
      placental uptake (y = 0.01x; R2 = 0.97). The placental permeability of TSH was
      2.4 x 10(-4) mL min(-1) g(-1) and was proportional to its coefficients of
      diffusion in water and molecular size. The transmembrane transfer and
      permeability of TSH was comparable to those of the placenta. We conclude that TSH
      crosses the human term placenta and fetal membranes sparingly.

PMID- 9585009
TI  - Accelerated maturation of fetal ductus arteriosus by maternally administered
      vitamin A in rats.
AB  - Maturation of fetal ductus arteriosus is associated with increased constriction
      in response to maternally administered indomethacin. Recently retinoic acid has
      been shown to be important in development of the fetal ductus arteriosus. To
      determine whether retinoid might be of value in the treatment of patent ductus
      arteriosus in premature infants, we studied the response of fetal ductus
      arteriosus to indomethacin with and without pretreatment with vitamin A (1 mg
      (3000 IU)/kg, intramuscular injection) in near-term and preterm rats. Maturation
      of the ductus arteriosus was studied by measuring the inner diameters of the
      ductus arteriosus (D) and main pulmonary artery (P) to get D/P ratio 4 h after
      orogastric administration of 1 mg/kg indomethacin. D/P was 1.0 in the fetus
      before administration of indomethacin. In near-term fetuses on the 21st d without
      vitamin A, D/P decreased to 0.54 with indomethacin, whereas it decreased to 0.27
      (p < 0.05) in those with pretreatment with vitamin A on the 19th and 20th d. In
      preterm fetuses on the 20th d without pretreatment with vitamin A, D/P decreased
      to 0.82 with indomethacin, whereas it decreased to 0.66 (p < 0.05) in those with
      pretreatment with vitamin A on the 19th d. It is concluded that maternally
      administered vitamin A accelerates maturation of the ductus arteriosus in fetal
      rats.

PMID- 9585010
TI  - Regulation of ductus arteriosus patency by nitric oxide in fetal lambs: the role
      of gestation, oxygen tension, and vasa vasorum.
AB  - We hypothesized that nitric oxide (NO) production by the fetal ductus arteriosus
      is limited because of low fetal PO2, but that at neonatal PO2, NO might be an
      important regulator of ductus arteriosus tone. We exposed isolated rings of fetal
      lamb ductus arteriosus to elevated PO2. L-NG-nitro-L-arginine methyl ester (L
      NAME), an inhibitor of nitric oxide synthase (NOS), and methylene blue and 6
      anilino-5,8-quinolinedione (LY83583), inhibitors of guanylate cyclase, produced
      constriction of the ductus arteriosus. When ductus arteriosus rings were exposed
      to low PO2, L-NAME had no effect, and methylene blue and LY83583 had only a small
      effect on ductus arteriosus tone. Sodium nitroprusside and calcium ionophore
      A23187 relaxed ductus arteriosus rings more than aortic rings, and relaxed ductus
      arteriosus rings from immature fetuses more than those from late gestation
      fetuses. In contrast, ductus arteriosus rings from both early and late gestation
      were equally sensitive to 8-bromo-cGMP. By both reverse transcriptase-polymerase
      chain reaction and immunohistochemistry, endothelial cell NOS and inducible
      calcium-independent NOS, but not nerve cell NOS, were detected in the ductus
      arteriosus. Inducible NOS was expressed only by endothelial cells lining the
      ductus arteriosus lumen; in contrast, endothelial cell NOS was expressed by both
      luminal and vasa vasorum endothelial cells. The role of inducible NOS in the
      ductus arteriosus is uncertain because the potency of a specific inducible NOS
      inhibitor in constricting the ductus arteriosus was negligible compared with that
      of an endothelial cell NOS inhibitor. We speculate that NO may be an important
      regulator of ductus arteriosus tone at high but not low PO2. The endothelial cell
      NOS isoform found in vasa vasorum may be an important source of NO because
      removal of ductus arteriosus luminal endothelium only partially blocks the
      effects of L-NAME, methylene blue, and LY83583.

PMID- 9585011
TI  - Antibody responses and opsonic activity in sera of preterm neonates with
      coagulase-negative staphylococcal septicemia and the effect of the administration
      of fresh frozen plasma.
AB  - Coagulase-negative staphylococcal septicemia is the most prominent nosocomial
      infection in neonatal intensive care units. Immaturity of host defenses in
      premature neonates is assumed to constitute an important risk factor.
      Opsonophagocytosis is considered to be the key host defense system against
      staphylococci with IgG antibodies as a major opsonin. For this reason we have
      studied serum IgG antibody titers and opsonic activity to coagulase-negative
      staphylococci in 20 infants with septicemia and 40 matched control subjects. In
      addition, we assessed the effect of administration of fresh frozen plasma (FFP)
      on IgG antibody titer and serum opsonic activity in 12 patients with septicemia.
      IgG antibodies, quantified by ELISA and opsonic activity, determined by flow
      cytometry, were expressed as a percentage of the value of pooled normal human
      reference serum. Both patients and control subjects showed low IgG titers
      (median, 21%; range, 1-192%) and a low opsonic activity (median, 33%; range, 8
      484%) at birth. During the first 2 postnatal wk IgG titers decreased
      significantly in septicemia patients (from a median of 30 to 17%, p = 0.025), but
      not in control subjects, whereas opsonic activity remained unchanged. The titer
      of IgG antibodies increased significantly in septicemia patients after FFP
      administration (from a median of 17 to 41%, p = 0.002), whereas the effect on
      opsonic activity was unpredictable, showing a moderate increase in 10 out of 12
      infants, and in 2 patients even a substantial decrease (>50%), despite adequate
      opsonic activity in the corresponding FFP batches. Immunoblotting of sepsis
      isolates with the corresponding patient sera demonstrated that septicemic infants
      may generate IgG antibodies against their blood isolate. Neonates who acquire
      coagulase-negative staphylococcal septicemia cannot be distinguished from control
      subjects on the basis of IgG antibodies and opsonic activity to staphylococci
      either at birth or during the first 2 postnatal wk. The administration of FFP to
      septicemia neonates has an unpredictable effect on opsonic activity and therefore
      does not seem to be a useful addition to antibiotic therapy.

PMID- 9585012
TI  - Effects of adenosine, ATP, and UTP on chloride secretion by epithelia explanted
      from fetal rat lung.
AB  - Catecholamines trigger the switch from liquid secretion to absorption by
      perinatal lung, but regulation of Cl- and liquid secretion by pulmonary epithelia
      early in lung development (low [catecholamine]) is unknown. We looked for
      evidence for P1 and P2 receptors that mediate Cl- secretion in 14-d distal lungs
      and 14- and 18-d tracheas explanted from fetal rats (term = 22 d). We measured
      amiloride-insensitive transepithelial voltage changes induced by ATP, UTP, or
      adenosine. Explants were hyperpolarized by all three agonists and by terbutaline,
      a beta-adrenergic agonist and Cl- secretagogue. Whereas adenosine, ATP, or UTP
      injected into 14-d explant lumena, or adenosine added to the tracheal bath,
      induced hyperpolarization with EC50 of 2-15 microM EC50, values for all three
      agonists in the distal lung bath or ATP or UTP in the tracheal bath were five
      times greater. By 18 d, EC50 values for agonists in the bath were comparable to
      those for lumenal agonists (3-12 microM). In contrast, microinjection of
      terbutaline into all explant lumena (final concentration = 3 x 10(-5) M) induced
      minimal hyperpolarization, whereas the same concentration in the bath raised
      bioelectric potential difference maximally. We conclude that 1) beta-adrenergic
      receptors are present on the basolateral membranes of cells of the pulmonary
      epithelium early in lung development, and 2) adenosine, ATP, and UTP receptors
      are present in apical membranes throughout lung epithelial development, but
      basolateral receptors for these agonists in distal lung or ATP/UTP in trachea
      function later in gestation. The putative distribution of P1 and P2 receptors
      suggests a role for agonists released from pulmonary epithelial cells in the
      regulation of liquid secretion early in lung development.

PMID- 9585013
TI  - Parathyroid hormone-related protein in tracheal aspirates of newborn infants.
AB  - PTH-related protein (PTHrP) is found with its receptor in a variety of normal
      mammalian embryonic tissues where it apparently regulates cellular growth and
      differentiation. PTHrP stimulates phosphatidylcholine synthesis in rat fetal lung
      explants, suggesting a role in fetal type II alveolar maturation and surfactant
      production. We investigated PTHrP levels in tracheal aspirates of newborn
      infants. We collected tracheal aspirates from 40 intubated newborn infants within
      the first 24 h of life. PTHrP levels were measured by a RIA using rabbit antisera
      to PTHrP peptide 38-64. We found significantly lower PTHrP levels in tracheal
      aspirates from infants born at less than 35 wk of gestation (p = 0.02) and with a
      birth weight less than 2 kg (p = 0.04). We also found significantly lower PTHrP
      levels in male preterm (<35 wk of gestation) infants compared with female infants
      (p = 0.01), and in preterm infants who required multiple doses of surfactant (p =
      0.005). Preterm infants exposed to antenatal steroids had significantly higher
      levels of PTHrP in tracheal aspirates (p = 0.02). PTHrP is associated with
      various indices of lung maturation and may prove to be a mediator of
      differentiation and growth.

PMID- 9585014
TI  - Protein composition of synthetic surfactant affects gas exchange in surfactant
      deficient rats.
AB  - Synthetic surfactant peptides offer an opportunity to standardize the protein
      composition of surfactant. We tested the effect of phospholipids (PL) with
      synthetic full-length SP-B1-78 (B), mutant B (Bser), KL4 peptide (UCLA-KL4), and
      palmitoylated SP-C1-35 (C) on oxygenation and lung function in a surfactant
      deficient rat model. Sixty-four adult rats were ventilated with 100% oxygen, a
      tidal volume of 7.5 mL/kg, and a rate of 60/min. Their lungs were lavaged with
      saline until the arterial PO2 dropped below 80 torr, when 100 mg/kg surfactant
      was instilled. Surfactant preparations included: PL (PL surfactant), PL + 3% B (B
      surfactant), PL + 3% B and 1% C (BC surfactant), PL + 3% UCLA-KL4 (KL4
      surfactant), PL + 3% Bser (Bser surfactant), and PL + 3% B and 1% UCLA-KL4 (BKL4
      surfactant). Sixty minutes after surfactant instillation, positive end-expiratory
      pressure was applied for 5 min, and pressure-volume curves were determined in
      situ. The six surfactant preparations had a minimum surface tensions <10 mN/m on
      a Langmuir/Wilhelmy balance. Instillation of PL, Bser, and BKL4 surfactant
      increased mean arterial/alveolar PO2 (aADO2) ratios by 50-100% over postlavage
      values, whereas KL4 surfactant increased aADO2 ratios by 118%, B surfactant by
      191%, and BC surfactant by 225%. Lung volumes at 30 cm H2O pressure were highest
      after treatment with BC surfactant, intermediate after B and KL4 surfactants, and
      lowest after BKL4, Bser, and PL surfactants. These data suggest that a surfactant
      preparation with a combination of synthetic B and C peptides surpasses synthetic
      B and KL4 surfactants in improving oxygenation and lung compliance in surfactant
      deficient rats.

PMID- 9585015
TI  - Maturational change in the cortical response to hypoperfusion injury in the fetal
      sheep.
AB  - A characteristic of perinatal encephalopathies are the distinct patterns of
      neuronal and glial cell loss. Cerebral hypoperfusion is thought to be a major
      cause of these lesions. Gestational age is likely to influence outcome. This
      study compares the cortical electrophysiologic and histopathologic responses to
      hypoperfusion injury between preterm and near term fetuses. Chronically
      instrumented 0.65 (93-99-d, n = 9) and 0.9 (119-133-d, n = 6) gestation fetal
      sheep underwent 30 min of cerebral hypoperfusion injury. The parasagittal
      cortical EEG and impedance (measure of cytotoxic edema) responses plus histologic
      outcome (3 d) were compared. The acute rise in impedance was similar in
      amplitude, but the onset was delayed (5.0 +/- 0.7 versus 9.1 +/- 1.1 min, p <
      0.05) in the preterm fetuses relative to those near term. In contrast the extent
      of the secondary rise was reduced (p < 0.01) and peaked earlier in the preterm
      fetuses (19.8 +/- 1.0 versus 40.5 +/- 3.5 h, p < 0.01). Both groups had a similar
      fall in EEG spectral edge frequency. The preterm fetuses had a milder loss of EEG
      intensity at 72 h (-7.7 +/- 1.5 versus -12.8 +/- 0.9 dB, p < 0.05). At both ages
      there was a predominantly parasagittal cortical distribution of damage with a
      similar pattern of neuronal loss in the thalamus and striatum. There was
      extensive selective neuronal loss within the upper layers of the cortex in those
      near term. In contrast the preterm fetuses developed subcortical infarcts (p <
      0.05). The cortical response to injury altered during the last trimester. The
      results suggest the severity of the delayed phase of cortical neuronal injury and
      selective neuronal loss increased near term. In contrast, the preterm fetuses had
      a more rapidly evolving injury leading to necrosis of the subcortical white
      matter.

PMID- 9585016
TI  - Regional distribution of prostaglandin H synthase-2 and neuronal nitric oxide
      synthase in piglet brain.
AB  - Immunohistochemical techniques were used to examine the distribution of
      prostaglandin H synthase (PGHS)-2 and neuronal nitric oxide synthase (nNOS) in
      piglet brain. Samples from parietal cortex, hippocampus, and cerebellum were
      immersion fixed in 10% formalin, sectioned at 50 microm, and immunostained using
      specific antibodies against PGHS-2 and nNOS. Immunoreactivity for PGHS-2 was
      extensive throughout the areas examined. For example, PGHS-2 immunoreactive cells
      were present in all layers of the cortex, but were particularly dense among
      neurons in layers II/II, V, and VI. In addition, glial cells associated with
      microvessels in white matter showed PGHS-2 immunoreactivity. In contrast, nNOS
      immunoreactive neurons were limited in number and widely dispersed across all
      layers of the cortex and thus did not form a definable pattern. In the
      hippocampus, heavy PGHS-2 immunoreactivity was present in neurons and glial cells
      in the subgranular region, stratum radiatum, adjacent to the hippocampal sulcus,
      and in CA1 and CA3 pyramidal cells. Immunostaining for nNOS displayed a different
      pattern from PGHS-2 in the hippocampus, and was mainly localized to the granule
      cell layer of the dentate gyrus and the mossy fiber layer. In the cerebellum,
      PGHS-2 immunoreactivity was heavily represented in the Bergmann glia and to a
      lesser extent in cells of the granular layer, whereas nNOS was detected only in
      Basket cells. There are four conclusions from this study. First, PGHS-2
      immunoreactivity is widely represented in the cerebral cortex, hippocampus, and
      cerebellum of neonatal pigs. Second, glia cells as well as neurons can show
      immunoreactivity for PGHS-2. And third, the distribution of nNOS is different
      from PGHS-2 immunoreactivity in the cerebral cortex, hippocampus, and cerebellum.

PMID- 9585017
TI  - Hypoxemic resuscitation in newborn piglets: recovery of somatosensory evoked
      potentials, hypoxanthine, and acid-base balance.
AB  - We tested the hypothesis that hypoxic newborn piglets can be successfully
      resuscitated with lower O2 concentrations than 21%. Severely hypoxic, 2-4-d-old,
      anesthetized piglets were randomly divided into five resuscitation groups: 21% O2
      (n = 10), 18% O2 (n = 9), 15% O2 (n = 9), 12% O2 (n = 8), all normoventilated,
      and a hypoventilated 21% O2 group (PaCO2; 7.0-8.0 kPa, n = 9). Base excess (BE)
      reached -20 +/- 1 mmol/L at the end of hypoxia. After 3 h of resuscitation, BE
      had risen to -4 +/- 1 mmol/L in the 21% O2, 18% O2, and hypoventilated groups,
      but was -10 +/- 2 mmol/L in the 15% O2 group (p < 0.05 versus 21% O2 group) and 
      22 +/- 2 mmol/L in the 12% O2 group (p < 0.05 versus 21% O2 group). Four animals
      died during resuscitation, all allocated to the 12% O2 group (p < 0.05 versus 21%
      O2 group). Somatosensory evoked potentials (SEPs) recovered in 39 of 45 piglets,
      and remained present during resuscitation in all except the 12% O2 group. SEP
      recovered initially even in six of eight animals in the 12% O2 group, but
      disappeared again in all later during resuscitation. The SEP amplitude recovered
      to levels not significantly different from the 21% O2 group in all groups except
      the 12% O2 group. Plasma hypoxanthine concentrations and extracellular
      hypoxanthine concentrations in the striatum decreased during resuscitation to
      levels not significantly different from the 21% O2 group in all but the 12% O2
      group (p < 0.05 versus 21% O2 group). In conclusion, severely hypoxic newborn
      piglets were resuscitated as efficiently with both hypoventilation and 18% O2 as
      with 21% O2.

PMID- 9585018
TI  - Dynamic changes in arousal threshold during sleep in the human infant.
AB  - Failure to arouse from sleep is a possible mechanism leading to sudden infant
      death. Using a controlled pulsatile air jet applied alternately to the nostrils
      we have made multiple measures of arousal threshold both between and within sleep
      states. Infants (n = 22) born at term were studied at 2-3 wk postterm (mean age
      13 d, range 9-17 d, study 1) and again at 2-3 mo postterm (mean age 78 d, range
      56-98 d, study 2). Arousal threshold (stimulus driving pressure, cm H2O) was
      determined in both active sleep (AS) and quiet sleep (QS). At both ages arousal
      threshold in QS was significantly higher (251 +/- 24 and 298 +/- 35) than in AS
      (163 +/- 19 and 144 +/- 29) (p < 0.001). In a morning sleep period, the first and
      second QS epochs were compared in each baby. In both study 1 and study 2,
      respectively, arousal thresholds were significantly higher in the second QS epoch
      (270 +/- 34 and 497 +/- 100) than in the first QS epoch (198 +/- 29 and 252 +/-
      69) (p < 0.05 and p < 0.02). There was a significant correlation in individual
      infants between arousal thresholds in the two states at both ages (p < 0.005 and
      p < 0.007, respectively). Regression analysis showed no correlation between the
      length of time the infant had been in a particular sleep state and the arousal
      threshold in either state in study 1 or in AS in study 2; however, arousal
      threshold increased significantly (p < 0.01) with time in QS in study 2. This
      study has expanded on previous findings that arousability is sleep state
      dependent by demonstrating that arousability in QS is also altered by the length
      of time that the infant has been asleep.

PMID- 9585019
TI  - Ventilatory control during exercise in normal children.
AB  - We investigated the relation between age and respiratory control during exercise
      in 80 children aged 6.4-17.6 y (42 male, age, 11.6 +/- 3.3 y; body weight, 41.3
      +/- 14.7 kg; and 38 female, age, 12.6 +/- 2.7 y; body weight, 42.5 +/- 9.3 kg).
      Exercise tests were performed on a treadmill after a standard symptom-limited
      Bruce protocol. Data were analyzed separately for boys and girls. At rest and at
      peak exercise, the ratio of minute ventilation to carbon dioxide production
      (VE/VCO2), the ratio of effective alveolar ventilation to carbon dioxide
      production (VA/VCO2), the ratio of pulmonary dead space to tidal volume (Vd/Vt),
      and arterial PCO2 (PaCO2) were not correlated with age. At the exercise intensity
      of ventilatory anaerobic threshold, the PaCO2 increased, and the VA/VCO2
      decreased, significantly with age, whereas the Vd/Vt was not related to age.
      Linear regression analysis demonstrated that the slope of the relationship
      between VE and VCO2 (deltaVE/deltaVCO2) and the slope of the relationship between
      VA and VCO2 (deltaVA/deltaVCO2) decreased with age. There were no gender
      differences in the regression slopes and the intercepts of the relationships.
      Results show that younger children breathe more during exercise to eliminate a
      given amount of CO2 to keep PaCO2 set point slightly but significantly lower than
      older children. This age dependence must be considered in investigating
      ventilatory control during exercise in children.

PMID- 9585020
TI  - Screening for bowel cancer. Overview.

PMID- 9585021
TI  - What can we conclude from the randomized controlled trials of fecal occult blood
      test screening?
AB  - The results of three published randomized controlled trials of fecal occult blood
      testing (FOBT) provide unequivocal proof of the principle that screening reduces
      mortality from colorectal cancer (CRC). However, several interesting questions
      remain in interpreting and applying the results of the clinical trials,
      including: how well does FOBT screening work (i.e. how much can CRC mortality be
      reduced), how does it work, when is it worthwhile and worthwhile doing, and how
      can technique be optimized? The answers to these questions have important
      practical and clinical implications.

PMID- 9585022
TI  - Screening for colorectal cancer: alternative faecal occult blood tests.
AB  - Hemoccult-based colorectal cancer (CRC) screening, while shown to be effective in
      randomized controlled trials, is suboptimal; alternative faecal occult blood
      tests which are either modifications of current guaiac-peroxidase tests or newer
      technologies (immunochemical), are available and show real promise. The goals of
      the alternative tests are improved sensitivity with acceptable specificity and
      improved compliance by screenees. The process of demonstrating superiority to
      Hemoccult need not include mortality as an endpoint, but must involve a direct
      comparison in large numbers of screenees (say 20,000) with cancer yields,
      apparent specificity and compliance determined for each test. Only the more
      sensitive and more readable guaiac test, HemoccultSENSA, and the immunochemical
      test Immudia-HemSp (the international version is HemeSelect) have undergone such
      extensive testing and could be considered as acceptable alternatives to Hemoccult
      for population-based screening. Even then, the test positivity rate of
      HemoccultSENSA warrants checking in a pilot study in the target population
      because it may pose a problem of specificity in some populations.

PMID- 9585023
TI  - Molecular approaches for colorectal cancer screening.
AB  - Molecular genetic approaches for colorectal cancer screening using stool samples
      have the potential to be very specific, sensitive and cost effective. K-ras
      oncogene mutation, observed in about 50% of the colorectal tumours, serves as an
      ideal target for such an approach. Several studies have shown that K-ras gene
      mutations present in the tumours can be detected from the stool of patients with
      colorectal cancer. The challenge for clinical application, however, is to develop
      a simple method for robust PCR amplification and a reliable assay for K-ras gene
      mutation detection in the stool samples.

PMID- 9585024
TI  - Flexible sigmoidoscopy as a mass screening tool.
AB  - Endoscopic removal of premalignant adenomas from the distal bowels of the entire
      population, 3 to 5-yearly from age 50, is advocated in the US as a feasible
      method of reducing colorectal cancer mortality rates. In the UK, a single
      flexible sigmoidoscopy (FS) is regarded as a more cost-effective option. Although
      more acceptable than colonoscopy, FS and polypectomy are expensive and invasive
      procedures carrying a small risk of serious harm. We believe that, before
      implementing mass screening, precise estimates are required of the magnitude of
      the reduction in mortality and costs (financial, physical and emotional). Several
      randomized trials, including a large British study, are currently evaluating
      these aspects.

PMID- 9585025
TI  - Colonoscopy as a mass screening tool.
AB  - There is strong evidence that population screening can reduce mortality from
      colorectal cancer. Screening tests such as faecal occult blood test and flexible
      sigmoidoscopy are used to identify patients with an increased risk of cancer who
      would benefit from a full colon examination. There is indirect evidence that
      colonoscopy may be effective as a mass screening tool. Potential benefits of
      colonoscopy include the ability to visualize the entire colon and to detect and
      remove polyps, which could prevent cancers, and identify cancers if present
      anywhere in the colon. Issues related to the implementation of a colonoscopy
      screening programme are discussed.

PMID- 9585026
TI  - The case for surveillance of high-risk' families.
AB  - Patients who have an elevated colorectal cancer risk on the basis of heritable
      susceptibility can be identified in two ways. First, family history information
      may indicate empirical risks approaching 50%, while assignment of relative risks
      of 2.0-4.0 to groups of patients fulfilling certain family history criteria is
      commonplace. Second, assessment of blood samples by mutation analysis of DNA
      mismatch repair genes that are known to be responsible for hereditary
      nonpolyposis colorectal cancer (HNPCC) now affords diagnostic assessment in
      increasing numbers of families. This review explores the issues involved in
      identifying families with genetic susceptibility to colorectal cancer and
      discusses the rationale for clinical screening in at-risk relatives.

PMID- 9585027
TI  - Nutritional factors in inflammatory bowel disease.
AB  - During the past 20 years there has been growing interest in the importance of
      nutritional factors in the pathogenesis of inflammatory bowel disease. There are
      so far no definite links between ulcerative colitis and diet, but links with
      Crohn's disease have been studied by both epidemiologists and clinicians.
      Epidemiological studies, although retrospective, have suggested that patients
      with Crohn's disease eat more sugar and sweets that control individuals; however,
      when dietary sugar is restricted, there is little clinical benefit. The clinical
      approach to nutrition in Crohn's disease has been by the use of elemental diets,
      which will produce symptomatic and objective remission in up to 90% of compliant
      patients. Those who return to normal eating soon relapse but, in some studies,
      have enjoyed prolonged remission on exclusion diets. The foods excluded have been
      not sugar, but predominantly cereals, dairy products and yeast. Attention has now
      switched to the possible harmful role of fat in Crohn's disease. The efficacy of
      elemental feeds appears to depend not on the presentation of nitrogen but on the
      amount of long chain triglyceride present. Increases in recent years in the
      frequency of Crohn's disease in Japan have been correlated with increased dietary
      fat intake, and a recent study suggested that W-3 fatty acids, which are
      metabolized by immunomodulatory leukotrienes and prostaglandins, may have a
      beneficial role to play. The links between nutrition and Crohn's disease have now
      become strong and the role of fat may be the most exciting of all.

PMID- 9585028
TI  - Non-pylori Helicobacter infections in humans.
AB  - The spectrum of human non-pylori Helicobacter infections is expanding. Evidence
      for the presence of bacteria such as H. heilmannii, H. felis, H. rappini, H.
      cinaedi, H. fennelliae and H. pullorum has been reported. These bacteria are
      likely to be associated with different clinical disorders. H. heilmannii is the
      most commonly described non-pylori Helicobacter in humans. Colonization with this
      bacterium is usually associated with mild gastritis. In some cases, gastric ulcer
      disease may occur. H. heilmannii are classified as such on the basis of
      morphological criteria. Recent phenotypical and genotypical data suggest that
      this is insufficient. Therefore, for a better understanding of the relation
      between non-pylori Helicobacter species and disease, there is a need for studies
      focusing on genetic instead of morphological criteria.

PMID- 9585029
TI  - Modern life' in the epidemiology of inflammatory bowel disease: a case-control
      study with special emphasis on nutritional factors.
AB  - OBJECTIVE: The rising incidence of inflammatory bowel disease (IBD) since the
      Second World War coincides with profound changes of the dietary pattern. The aim
      of the study was to investigate the possible pathogenic role of some
      characteristic 'modern life' dietary factors in IBD. DESIGN: Case-control,
      studying risk factors in recently diagnosed cases, 290 with Crohn's disease and
      398 with ulcerative colitis, compared with 616 population controls. Smoking, age,
      gender and education were taken into account by using logistic regression
      analysis. SETTING: Hospital cases and population controls. INTERVENTIONS:
      Questionnaires. MAIN OUTCOME MEASURES: Logistic regression-derived odds ratios.
      RESULTS: A positive association with cola drinks [OR: 2.2 (95% CI 1.5-3.1)],
      chewing gum [OR: 1.5 (95% CI: 1.1-2.1)] and chocolate consumption [OR: 2.5 (95%
      CI: 1.8-3.5)] and a negative association with citrus fruit consumption [OR: 0.5
      (95% CI 0.3-0.7)] and the development of Crohn's disease were found. Consumption
      of cola drinks [OR: 1.6 (95% CI 1.1-2.3)] and chocolate consumption [OR: 2.5 (95%
      CI 1.8-3.5)] were positively associated with developing ulcerative colitis. There
      was a negative association between the intake of citrus fruits [OR: 0.5 (95% CI
      0.4-0.8)] and 'having a stuffed pet' for a period longer than 5 years [OR: 0.6
      (95% CI 0.4-0.9)] and developing the disorder. No association with the frequency
      of tooth brushing and developing IBD was found. CONCLUSION: All the nutritional
      items mentioned may be true risk factors or they just might be the expression of
      a modern life-style also involving other risk factors for the development of IBD
      which at the present are still unknown.

PMID- 9585030
TI  - Gastric ulcers and Helicobacter heilmannii.
AB  - OBJECTIVE: To compare 14 patients with gastric ulcer and Helicobacter heilmannii
      with other patients with gastric ulcer: age and sex matched patients, patients
      colonized by Helicobacter pylori and patients on nonsteroidal anti-inflammatory
      drugs (NSAIDs). SETTING: The endoscopy unit of a university-affiliated hospital.
      PATIENTS AND METHODS: All patients underwent endoscopy with two antral biopsies
      and smears from biopsies (touch cytology) in addition to biopsies of ulcers. Most
      patients had fundic biopsies (n = 10), antral biopsies for culture (n = 7) and/or
      a urease test (n = 9). Serologic determination of antibodies against H. pylori
      was obtained in nine patients. RESULTS: Patients with H. heilmannii diagnosed on
      smears from biopsies (touch cytology) had multiple and antral ulcers in 11
      samples, and nodular or irregular lesions in five samples. No patient had a
      history of peptic ulcer disease. Biopsy revealed mild chronic gastritis in all
      patients, with features of reactive gastritis in nine. No patient had coexistent
      infection with H. pylori. Only two of ten patients with follow-up endoscopies had
      persistent H. heilmannii infection on smear or biopsy. No patient had symptomatic
      recurrence. Patients with H. pylori infection were older and often had recurrent
      ulceration. The majority of ulcers associated with NSAIDs occurred in elderly
      women. CONCLUSIONS: Newly diagnosed gastric ulcers are associated with H.
      heilmannii infection. Healing is associated with the disappearance of H.
      heilmannii and the regression of reactive gastritis. Ulcers differ from those
      associated with H. pylori infection or with the use of NSAIDs, suggesting that H.
      heilmannii is a possible cause of gastric ulcers.

PMID- 9585031
TI  - Liver biopsy pathology in human immunodeficiency virus infection.
AB  - OBJECTIVES: To determine the hepatic changes in patients with human
      immunodeficiency virus (HIV) infection in Dublin and to assess the usefulness of
      liver biopsy in this condition. DESIGN: A consecutive series of liver biopsies
      was examined retrospectively and correlated with clinical findings. METHODS: A
      histological review was conducted of specimens from all patients who had
      undergone liver biopsy in a tertiary referral centre for HIV-infected patients in
      Dublin. RESULTS: Thirty-nine liver biopsies were studied from 36 patients. Thirty
      one (86%) showed pathological changes. Non-specific changes were most frequent,
      followed by viral-induced chronic hepatitis (15 cases). Acute hepatitis was
      documented in five and cirrhosis in four cases. Five biopsies performed for
      pyrexia of unknown origin (PUO) or suspected tuberculosis showed granulomas.
      Organisms were rarely identified (2) and bile duct changes were uncommon.
      CONCLUSIONS: Liver biopsy was useful in detecting primary hepatic pathology and,
      in some cases, the cause of PUO, but not useful in detecting opportunistic
      infections despite their known presence in other organs.

PMID- 9585032
TI  - Serological markers for coeliac disease: changes with time and relationship to
      enteropathy.
AB  - Antigliadin antibodies (AGA) may be present in healthy adults. One previous study
      has reported that IgA-AGA detected by population screening may become negative
      after a 6-year follow-up period. OBJECTIVES: To determine the variability of
      coeliac disease-associated antibodies with time and to ascertain which antibodies
      are predictive of the presence of enteropathy. DESIGN: A clinical follow-up study
      of subjects with positive serological markers detected by screening at the time
      of the Belfast MONICA Project. METHODS: Jejunal biopsies were carried out
      endoscopically by means of a Crosby capsule. IgA-antigliadin was detected by a
      commercial ELISA; IgA-antiendomysial and antireticulin antibodies were determined
      by indirect immunofluorescence. RESULTS: Of 48 subjects followed up after 4
      years, 28 (58%) had developed negative serology and 20 (42%) had persistently
      positive serology. Thirteen of 20 subjects with persistent serology had villous
      atrophy. Of 68 subjects followed up after 13 years, 32 (47%) had developed
      negative serology and 36 (53%) had persistent serology. Of 10 subjects with
      persistent serology who were biopsied, four had villous atrophy. None of the
      subjects who developed negative serology were found to have coeliac disease.
      CONCLUSIONS: Persistence of serological markers as a follow-up to a population
      screening programme may predict enteropathy in some subjects, whereas subjects
      who develop negative serology may be reassured. Subjects with persistent serology
      and normal histology require follow-up to determine if these markers are
      indicative of latent coeliac disease.

PMID- 9585033
TI  - Which Helicobacter pylori-positive dyspeptics are likely to respond
      symptomatically to empirical H. pylori eradication?
AB  - OBJECTIVE: To identify which Helicobacter pylori-positive dyspeptic patients have
      an increased likelihood of having peptic ulcer and may thus be more likely to
      benefit from empirical H. pylori eradication therapy. METHODS: 622 out of 740
      consecutive dyspeptic subjects (median age 45 years, range 14-91, 51% male)
      attending for rapid access endoscopy were eligible for the study. Demographic
      data and endoscopic findings were recorded. H. pylori status was determined by
      urease and histology. RESULTS: In all age groups, peptic ulcers were commoner in
      males than females [44% (85/195) vs 23% (32/139), P < 0.001] and in smokers than
      non-smokers [47% (46/97) vs 32% (50/159), P < 0.05]. Males, heavy smokers and
      those with a family history of peptic ulcer had increased adjusted odds of having
      a peptic ulcer (2.59, 1.96 and 1.90, respectively). Corresponding odds ratios for
      those aged under 45 were 2.59, 0.94 and 2.52. In H. pylori-positive dyspepsia,
      being a male who either smoked heavily or had a family history of peptic ulcer
      gave a sensitivity and positive predictive value for peptic ulcer of 86 and 45%
      for all age groups and 85 and 49% for those aged under 45. CONCLUSION: Male H.
      pylori dyspeptics who smoke >10 cigarettes per day and/or have a family history
      of peptic ulcer are likely to have peptic ulcer and are thus likely to benefit
      from empirical eradication therapy.

PMID- 9585034
TI  - Graves' hyperthyroidism in a patient with primary sclerosing cholangitis.
      Coincidence or combined pathogenesis?
AB  - Several autoimmune disorders have been associated with the diagnosis of primary
      sclerosing cholangitis (PSC). We report on a 19-year-old male PSC patient with a
      history of ulcerative colitis who developed hyperthyroidism consistent with
      Graves' disease. In contrast to primary biliary cirrhosis, hyperthyroidism
      appears to be very uncommon in PSC patients. Nevertheless, the rarity of Graves'
      disease in young males, the presence of a human leucocyte antigen (HLA) phenotype
      often encountered in both Graves' disease and PSC and the presence of several
      autoantibodies suggest a common immunogenetic predisposition, rather than mere
      coincidence, of both diseases in this patient. Since many patients with thyroid
      disease exhibit mild cholestatic liver function abnormalities but few of them
      undergo cholangiographic examination, PSC may be underdiagnosed. Physicians
      should therefore be aware of the potential association between thyroid disease
      and PSC.

PMID- 9585035
TI  - Self-expanding, metal stents for malignant colonic obstruction.

PMID- 9585036
TI  - Pictorial review: ultrasonography of primary bone tumours.
AB  - We present our experience with the use of ultrasonography in the assessment of
      suspected primary or recurrent bone tumours of the appendicular skeleton and
      pelvis in 73 patients. Ultrasound can effectively assess the extraosseous
      component of malignant and aggressive benign lesions and those tumours arising
      from the surface of the bone. Periosteal reaction, cortical destruction,
      pathological fracture, matrix mineralization, fluid-fluid levels and involvement
      of the neurovascular bundle are all identified. Despite this, we could not
      identify any advantage of ultrasound compared to plain radiography or magnetic
      resonance imaging in diagnosis and local staging. However, ultrasound was found
      to be of great value in guiding percutaneous needle biopsy.

PMID- 9585037
TI  - Congenital uro-nephropathies: is routine voiding cystourethrography always
      warranted?

PMID- 9585038
TI  - Self-expanding metal stents in the management of colorectal carcinoma--a
      preliminary report.
AB  - AIMS: The role of diagnostic imaging in colorectal carcinoma is in the initial
      diagnosis, staging and detection of complications of the disease. Seven cases of
      colorectal carcinoma are presented where expandable metallic stents were placed
      for the management of stenosing lesions in patients with advanced metastatic
      disease or with serious medical complications which prevented immediate surgery.
      RESULTS: Seven patients (five male, two female) with an age range of 51-76 years
      had expandable metallic stents placed over a 9-month period. All stents were
      placed successfully with no immediate complications. The stents remained in situ
      for a range of 7-210 days. CONCLUSION: Expandable metallic stents can be
      successfully and safely placed in the colon. These stents may be useful in the
      management of patients with advanced metastatic disease or in those presenting
      with large bowel obstruction in which decompression by a stent allows treatment
      of coexisting medical complications to enable surgery to be carried out at a
      later date.

PMID- 9585039
TI  - Invasive aspergillosis in the immunocompromised host: utility of computed
      tomography and bronchoalveolar lavage.
AB  - OBJECTIVE: Bronchoalveolar lavage is performed almost routinely in
      immunocompromised patients with suspected pneumonia, but it has a low yield in
      the diagnosis of pulmonary aspergillosis. The aim of this study was to determine
      whether computed tomography (CT) is helpful in determining the likelihood of a
      positive bronchoalveolar lavage by allowing distinction of patients with
      angioinvasive aspergillosis from those with Aspergillus bronchopneumonia. METHODS
      AND RESULTS: A retrospective study was performed including consecutive
      immunocompromised patients with suspected pneumonia who underwent CT scanning of
      the chest and bronchoalveolar lavage and who had definite diagnosis of pulmonary
      aspergillosis. The CT scans were reviewed by two chest radiologists and
      classified as showing features consistent with angioinvasive or airway invasive
      aspergillosis. Twenty-one patients met the inclusion criteria. Bronchoalveolar
      lavage was positive for fungi in two of 11 patients with CT findings consistent
      with angioinvasive aspergillosis and eight of 10 patients with CT scans
      consistent with Aspergillus bronchopneumonia (P < 0.01, chi-squared test). CT
      findings of angioinvasive aspergillosis included nodules measuring 1-3.5 cm in
      diameter in six, segmental consolidation in three, and both nodules and segmental
      consolidation in two patients. CT findings of Aspergillus bronchopneumonia
      including peribronchial consolidation in five, small centrilobular micronodules
      in one, and both in four patients. CONCLUSIONS: Chest CT is helpful in
      determining the likelihood of successful diagnosis of pulmonary aspergillosis by
      bronchoalveolar lavage.

PMID- 9585040
TI  - Radiological appearances of lymphomas arising from mucosa-associated lymphoid
      tissue (MALT) in the lung.
AB  - We review the radiological findings in 13 patients with histologically proven (n
      = 10) or clinically diagnosed (n = 3) lymphomas arising in mucosa-associated
      lymphoid tissue (MALT) of the lung. These rare B-cell lymphomas typically follow
      an indolent course, and many cases are still being incorrectly described in
      current radiological literature under the term pseudolymphoma. The patients
      frequently give a history of autoimmune disease involving the affected organ, and
      involvement of another mucosal site as part of a disseminated MALT lymphoma, is
      common. The radiographic patterns of pulmonary parenchymal involvement in lung
      MALT lymphomas have been reviewed, and correlation made with their clinical
      behaviour.

PMID- 9585041
TI  - Comparison between planar and tomographic radionuclide ventriculography for
      detecting inferior wall motion abnormalities.
AB  - Gated planar radionuclide ventriculography is routinely used for the detection of
      regional wall motion abnormalities of the left ventricle. However, for inferior
      wall motion abnormalities, sensitivity is known to be low in the left anterior
      oblique 'best septal' projection, although improved if a left posterior oblique
      (LPO) view is also acquired. Gated tomography of the cardiac blood pool is now
      available. This study compared the sensitivity of planar 'best septal'
      projection, LPO and tomographic radionuclide ventriculography in the detection of
      inferior wall motion abnormalities. Thirty-two patients consisting of 18 with
      previous inferior myocardial infarction and 14 normal controls were studied. All
      patients underwent equilibrium planar 'best septal', planar LPO and then
      tomographic radionuclide ventriculography. Inferior wall motion abnormality was
      detected in 'best septal' in eight (44%) patients, LPO in 12 (67%) and tomography
      in 17 (94%) patients, respectively. Tomographic radionuclide ventriculography was
      best at detecting inferior wall motion abnormality while planar LPO projection is
      better than 'best septal' projection.

PMID- 9585042
TI  - Radiological malformations of the ear in Pendred syndrome.
AB  - Pendred syndrome comprises the association of severe congenital sensorineural
      deafness with thyroid pathology. Although it is the commonest form of syndromic
      hearing loss, the primary genetic defect remains unknown. The variable clinical
      presentation allied to the difficulty in securing the diagnosis have resulted in
      relatively poor documentation of the radiological features of this syndrome. We
      now present data on 40 patients, all complying with strict diagnostic criteria
      for the disorder, and describe our experience of the prevalence of specific
      malformations of the inner ear as well as comparing the relative merits of
      computed tomography (CT) and magnetic resonance imaging (MRI) in the
      investigation of this inherited condition. Deficiency of the interscalar septum
      in the distal coils of the cochlea (Mondini deformity) was found to be a common
      but probably not a constant feature of Pendred syndrome. However, enlargement of
      the endolymphatic sac and duct in association with a large vestibular aqueduct
      was present in all 20 patients examined by MRI. We conclude that thin section
      high resolution MRI on a T2 protocol in the axial and sagittal planes is the
      imaging investigation of choice.

PMID- 9585044
TI  - Carbon dioxide enhanced ultrasonography of hepatic haemangiomas.
AB  - The purpose of this study was to characterize the imaging manifestations of
      carbon dioxide enhanced ultrasonography (CO2US) in hepatic haemangiomas. CO2US
      was performed for 52 haemangiomas in 25 patients and for 352 various hepatic
      nodules in 192 patients. Characteristic enhancement patterns for hepatic
      haemangiomas were noted. All 39 large haemangiomas (> 1 cm) demonstrated
      peripheral nodular enhancement in the early and parenchymal phases associated
      with delayed washout character (> 30 min). Centripetal fill-in of CO2 was noted
      in 82.1% of large haemangiomas. Two enhancing patterns were noted in 13 small
      haemangiomas (< 1 cm): peripheral nodular (69.2%) and homogeneous (30.8%).
      Delayed washout was also noted in all small haemangiomas. Centripetal fill-in of
      CO2 was hard to define in small haemangiomas. None of the other 352 hepatic
      nodules had the same imaging features. In conclusion we found that CO2US is
      valuable in differentiating hepatic haemangiomas from other liver tumours in
      clinically doubtful cases.

PMID- 9585043
TI  - Comparison of accuracy of scintimammography and X-ray mammography in the
      diagnosis of primary breast cancer in patients selected for surgical biopsy.
AB  - Mammography, whilst remaining the first line imaging investigation of suspected
      primary breast cancer, can be difficult to interpret in patients with fibrous or
      dense breasts. Radionuclide imaging of the breast (scintimammography) has been
      suggested as an additional test. The aim of this study was to perform
      prospectively a comparison of the two techniques in a population with suspected
      breast cancer. Seventy such patients, mean age 54 years (range 57 years, 28-85)
      with 74 suspicious breast lesions were studied. They were imaged 5-10 min after
      intravenous injection of 740 MBq of Tc-99m sestamibi. Prone lateral and anterior
      supine views with and without markers were performed. All patients had
      histological confirmation of the nature of the breast lesions by limited
      incisional biopsy or definitive wide local excision, or cytological confirmation
      on fine needle aspiration. All patients had X-ray mammography. There were 53
      malignant breast tumours and 21 benign lesions. Scintimammography correctly
      diagnosed 47 breast cancers, and yielded true-negative results in 12 benign
      breast lesions. There were six cases of false-negative results and nine false
      positive results. Four scans were reported as equivocal. The sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      were 89%, 52%, 84% and 67%, respectively. X-ray mammography diagnosed correctly
      37 malignant tumours, and in 12 benign lesions the results were true negatives.
      Ten studies were reported as equivocal. The sensitivity, specificity, PPV and NPV
      were 70%, 57%, 80% and 43%, respectively. The accuracy of Tc-99m sestamibi
      scintimammography was better than X-ray mammography though this was not
      significant (McNemar's test). Fewer equivocal results were obtained with
      scintimammography. Scintimammography may therefore have a role in the diagnosis
      of primary breast cancer when X-ray mammography is equivocal or unhelpful.

PMID- 9585045
TI  - Ultrasound in the assessment of metatarsalgia: a surgical and histological
      correlation.
AB  - AIMS: To assess the reliability of ultrasound in the evaluation of metatarsalgia
      in a typical clinical setting. METHODS AND MATERIALS: The clinical records,
      ultrasound findings, surgical outcome and histology of patients with
      metatarsalgia referred for ultrasound evaluation were reviewed. All ultrasound
      examinations were performed by the same operator via a plantar approach using
      high resolution linear array probes. RESULTS: Thirty-seven patients were
      examined, age range 23 to 74, mean 49.6 years; thirty-one were female. Thirty
      seven intermetatarsal masses were found in 32 patients. To date 26 patients have
      undergone surgery and 28 lesions (26 Morton's neuromas, one angiolipoma and one
      angioleiomyoma) have been excised. There were no false-positive ultrasound
      examinations. A solitary neuroma was missed. Sensitivity was 96% and positive
      predictive value 100%. CONCLUSION: Ultrasound is a valuable tool in the
      evaluation of metatarsalgia and has high sensitivity and positive predictive
      value for the detection of intermetatarsal masses. It provides exact localization
      prior to surgical resection and detects unsuspected additional lesions.

PMID- 9585046
TI  - US findings of xanthogranulomatous cholecystitis.
AB  - The ultrasound (US) scans of eleven patients with histologically proven
      xanthogranulomatous cholecystitis have been reviewed. The thickness of the
      gallbladder (GB) wall, echogenicity of the thickened GB wall, the presence of
      intramural nodules, gallstones, pericholecystic fluid, loss of wall definition
      with the liver, and intrahepatic ductal dilatation were specifically assessed by
      two radiologists. The range of thickness of the GB wall was 3-20mm (mean, 11.2
      mm). Thickening was diffuse in nine cases and focal in two. The thickened GB
      wall, excluding intramural nodules, was echogenic in seven, isoechoic in three
      and hypoechoic in one, compared with hepatic echogenicity. Intramural nodules
      were found in eight cases. These were discrete, oval or flat, and of low
      echogenicity. These ranged in size from 6 to 12 mm (mean, 10.5 mm). Gallstones
      were present in six cases and there was intrahepatic duct dilatation in two of
      these. Definition between the liver and the GB was obliterated in seven cases.
      One case of GB perforation, confirmed at operation, demonstrated pre-operatively
      a GB wall defect and connection with the surrounding pericholecystic fluid.
      Pericholecystic fluid was absent in the other 10 cases. Xanthogranulomatous
      cholecystitis presents ultrasonically as GB wall thickening, and the majority of
      cases in this series also demonstrated intramural hypoechoic nodules. These
      findings can be helpful in the diagnosis of xanthogranulomatous cholecystitis.

PMID- 9585047
TI  - Trends in the use of pelvimetry techniques.
AB  - Assessment of maternal pelvic dimensions is usually considered necessary where
      vaginal delivery is contemplated in a breech presentation or if reduced pelvic
      dimensions are suspected in a current or previous pregnancy. Pelvimetry
      techniques include computed tomography (CT), conventional radiography, digital
      fluorography and magnetic resonance imaging (MRI). The first three techniques
      result in a radiation dose to mother and fetus which, depending on how the
      technique is performed, can vary by up to 40-fold. Of the techniques using X
      rays, CT pelvimetry with a lateral scanogram generally gives the lowest radiation
      dose and conventional radiography using an air gap technique with a single
      lateral view is a relatively low-dose alternative where CT is not available. A
      questionnaire was sent to 227 hospitals during 1993 and 1996 to assess whether
      there was a move towards lower dose techniques of pelvimetry. The results show a
      trend away from conventional pelvimetry (48.4% in 1993 to 28% in 1996) with a
      small proportion of centres using MRI (4%) in 1996. Of the centres still using
      conventional pelvimetry, relatively few were using a low-dose air-gap technique
      (2.1% in 1993 to 10.9% in 1996). An increasing majority of centres were using one
      view CT (69.3% in 1993 and 80.4% in 1996) but a significant proportion were still
      performing more than one view. This study shows that there was a move towards
      lower dose techniques of pelvimetry but that there were still many hospitals that
      had not implemented a policy of reducing radiation exposure in these patients.

PMID- 9585048
TI  - Calcific tendinitis of the gluteus maximus tendon with abnormalities of cortical
      bone.
AB  - Calcific tendinitis of the gluteus maximus tendon is unusual and only eight cases
      associated with erosions of cortical bone have been reported. We present three
      further cases which demonstrate variation in appearances of the amorphous
      calcification in the tendon and cortical erosions on plain radiographs. Isotope
      bone scans show focal increased activity and computed tomography (CT) clearly
      demonstrates erosion of cortical bone and calcification within the tendon
      insertion of gluteus maximus. Follow-up examinations in two cases demonstrated
      resolution of the changes. We believe this series demonstrates the radiological
      features and natural history of a common condition occurring at an unusual site.
      Its recognition is important in order to avoid unnecessary surgical intervention.
      Resolution of the calcification and cortical erosions has not been previously
      described.

PMID- 9585049
TI  - Case report: tracheobronchopathia osteochondroplastica.

PMID- 9585050
TI  - Case report: the CT features of orbital multiple myeloma.

PMID- 9585051
TI  - Case report: computed tomography demonstration of inferior vena caval thrombosis
      and incorporation into an abdominal aortic aneurysm.

PMID- 9585052
TI  - Case report: amoebic abscess of the brain.

PMID- 9585053
TI  - Metformin and contrast: the risk.

PMID- 9585054
TI  - Spiral CT and pulmonary embolism.

PMID- 9585055
TI  - CTAP and MRI.

PMID- 9585056
TI  - Cloning of a breakpoint cluster region on chromosome 14 in uterine leiomyoma.
AB  - A recurrent reciprocal chromosomal translocation, t(12;14)(q15;q24) is frequently
      observed in uterine leiomyoma. Chromosome 12 breakpoints have been shown to occur
      in a region of approximately 150 kb that contains the gene for a high mobility
      group protein (HMGI-C). The breakpoint region on chromosome 14 has not been
      precisely defined. We have generated a contig of overlapping yeast artificial
      chromosome (YAC) clones approximately 3 Mb in size. Fluorescence in situ
      hybridization (FISH) analysis showed that this contig spanned the t(12;14)
      breakpoints in three uterine leiomyomas and that the breakpoints in these tumors
      occurred within a 1 Mb region. A 30 kb cosmid spanning one of the breakpoints was
      isolated to set the stage for identifying regions on chromosome 14 that may cause
      this region to be a preferential site for chromosomal translocation.

PMID- 9585057
TI  - Monoclonal antibodies to taxanes that neutralize the biological activity of
      paclitaxel.
AB  - Recently it has been proposed that drug-specific neutralizing antibodies may
      limit side-effects that occur during chemotherapy. These studies were undertaken
      to determine if monoclonal antibodies, 3C6 specific to paclitaxel and 8A10
      specific to taxane diterpenes, are inhibitors of paclitaxel-induced inhibition of
      proliferation and cellular microtubule and nuclear changes. The results show that
      3C6 and 8A10 each inhibit paclitaxel-induced cytotoxicity, microtubular bundling,
      stabilization from vinblastine-induced microtubule depolymerization and the
      formation of micronuclei. We conclude that these antibodies effectively
      neutralize paclitaxel activity in vitro and that they may be useful to determine
      if antibody-blocking strategies can prevent dose-limiting toxicities.

PMID- 9585058
TI  - Effect of iron overload on the benzoyl peroxide-mediated tumor promotion in mouse
      skin.
AB  - In this communication, we report that iron overload augments benzoyl peroxide
      (BPO)-mediated tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated
      mouse skin. Female albino Swiss mice were overloaded with iron and tumors were
      initiated by applying a single topical application of DMBA. A week after the
      initiation, promoting agent, BPO, was applied three times/week for 46 weeks. The
      appearance of the first tumor (papilloma) and the number of tumors/mouse were
      recorded. When compared to the control group, the iron-overloaded mice showed an
      increased incidence of tumors at various time intervals. In iron-overloaded
      animals, tumors appeared earlier and also the number of tumors/mouse was
      significantly higher. These data could be correlated with the iron levels of
      mouse skin in the two groups. Further, BPO-mediated induction in ornithine
      decarboxylase (ODC) activity and [3H]thymidine incorporation in cutaneous DNA
      were higher in the iron overload group. In addition, in iron-overloaded mice,
      cutaneous lipid peroxidation (LPO) and xanthine oxidase (XOD) activities were
      higher, whereas catalase activity was reduced. Similar to papilloma induction, a
      significant increase in carcinoma yield and incidence was observed in iron
      overloaded animals. Based on this study, we propose that iron overload
      significantly increases the tumor promotion and progression potential of BPO. We
      suggest that oxidative stress generated by iron overload is responsible for the
      augmentation of BPO-mediated cutaneous tumorigenesis.

PMID- 9585059
TI  - Investigation of p53, c-erbB-2, PCNA immunoreactivity, DNA content, AgNOR and
      apoptosis in bladder carcinoma as prognostic parameters.
AB  - The association between known prognostic variables such as TNM stage,
      histological grade and mutant p53 tumor suppressor gene product, c-erbB-2
      oncoprotein, DNA ploidy and cell kinetic data, including mitoses, PCNA
      expression, AgNOR scores and apoptosis, was investigated in 29 transitional cell
      carcinoma (TCC) cases. A positive correlation between the histologic grade and
      all the studied parameters, except for c-erbB-2 expression, and a positive
      correlation between the stage and histological grade, DNA ploidy, mitoses,
      apoptosis and p53 expression were found. The results of this study are in
      accordance with some of the previous studies, except for apoptosis which had been
      studied for the first time in TCCs. Although we found a statistically significant
      correlation between the apoptosis and both tumor stage and histological grade,
      the predictive value of apoptosis as an independent prognostic factor remains to
      be established in a larger series.

PMID- 9585060
TI  - Differential modulation by dietary n-6 or n-9 unsaturated fatty acids on the
      development of two murine mammary gland tumors having different metastatic
      capabilities.
AB  - It is widely known that dietary lipids can modify the ability of different
      cancers to grow up and metastasize, especially mammary gland tumors. However, it
      is still unclear whether n-6 fatty acids behave as tumor promoters in this gland
      cell population. The effect of different nutritional polyunsaturated fatty acids
      (PUFAs) on tumor growth parameters of two transplantable murine mammary gland
      adenocarcinomas of low and high metastatic ability was tested on hosts fed diets
      with corn oil (CO) rich in 18:2n-6, evening primrose oil (EPO) containing 18:3n-6
      (GLA) and a third formula supplemented with olein (O) 18:1n-9, which induces an
      essential fatty acid deficiency (EFAD). Tumor growth parameters were not
      adversely affected in the corn oil group with respect to stock-fed controls.
      Furthermore, metastatic spreading diminished in this group. EPO showed a moderate
      antitumor activity whereas the n-9-enriched diet showed no clear-cut effects. In
      both mammary gland tumors, n-6 fatty acid-rich lipids formulae, containing GLA
      and linoleic acid, were not tumor promoters. On the contrary, both exhibited
      anticancer activity.

PMID- 9585061
TI  - Increased telomerase activity and absence of p53 mutation in oligoastrocytomas
      induced by N-ethyl-N-nitrosourea in rats.
AB  - The question of whether the changes in telomerase activity and/or the alteration
      of the p53 gene are involved in the development of oligo-astrocytomas induced by
      N-ethyl-N-nitrosourea (ENU) in rats was addressed. Telomerase activity levels of
      oligo-astrocytomas, including early neoplastic lesions, were significantly
      increased as compared to the normal controls, correlating with the degree of
      malignancy. In contrast, no mutations of p53 exons 5-7 were found in early
      neoplastic lesions or oligo-astrocytomas. These results indicate that the
      activation of telomerase occurs during astrocytoma carcinogenesis and contributes
      to the development of brain tumors, but the alterations of p53, at least on exons
      5-7, may not be involved in this process.

PMID- 9585062
TI  - Changes in expression of the antigen recognized by monoclonal antibody A7 in
      human pancreatic carcinoma cells following exposure to anticancer agents.
AB  - Techniques which can increase the expression level of tumor-associated antigens
      may improve immunotargeting therapy. We studied the reactivity of MAb A7 toward
      an antigen expressed on the surface of the human pancreatic cancer cell line HPC
      YS after treatment with various antitumoral agents. When we applied 1 microg/ml
      mitomycin C (MMC) or 0.1 microg/ml neocarzinostatin (NCS) for 1 h, A7 recognizing
      antigen expression was enhanced until 24 h after the treatments. At a dose that
      completely suppressed cell growth, increased antigen expression was maintained
      for 96 h. Therefore, this study suggests that the combined application of an
      anticancer drug and MAb A7 may be useful for immunotargeting chemotherapy.

PMID- 9585063
TI  - The inhibitory effect of vitamin E on 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone-induced lung tumorigenesis in mice based on the regulation of polyamine
      metabolism.
AB  - The present study was carried out in order to estimate a usefulness of vitamin E
      against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung
      tumorigenesis in mice. Feeding high doses of vitamin E suppressed the NNK-induced
      elevation of the activity of ornithine decarboxylase, a key enzyme of polyamine
      biosynthesis, in the lungs of mice at 4 weeks after injection. In contrast, the
      vitamin elevated the NNK-induced decrease of the activity of spermidine/spermine
      N1-acetyltransferase, a key enzyme of polyamine biodegradation. In conjugation
      with these events, the NNK-increased level of proliferating nuclear cell antigen
      as a marker of cell proliferation was suppressed by vitamin E treatment. Also,
      the supply of high doses of vitamin E suppressed NNK-induced lung tumorigenesis
      in mice. These results suggest that vitamin E inhibits the development of lung
      tumors in mice treated with NNK, partly due to the regulation of polyamine
      metabolism.

PMID- 9585064
TI  - Role of K-ras mutations in colorectal carcinoma.
AB  - In order to investigate whether two common types of colorectal cancer with
      different gross appearances share the same incidence of K-ras mutation, the
      occurrence of a point mutation in codon 12 or codon 13 of the K-ras oncogene was
      determined in 50 cases of colorectal carcinoma. The PCR technique was employed,
      followed by RFLP analysis and sequencing to identify specific point mutations. No
      correlation was found between the presence of a K-ras gene mutation and
      histological parameters. A strong association was found between K-ras mutations
      and the gross polypoid appearance of colorectal carcinoma (polypoid 73% versus
      ulcerative 8%). The results indicate a preferential association with the K-ras
      oncogene involved in polypoid type colorectal carcinoma.

PMID- 9585065
TI  - Doxorubicin induced expression of P-glycoprotein in a canine osteosarcoma cell
      line.
AB  - Canine and human osteosarcoma are very similar with respect to clinical
      presentation, radiological and histopathological features, metastatic rate and
      pattern and response to therapy. For these reasons, canine osteosarcoma is a
      useful intermediate model for the disease in humans. Overexpression of P
      glycoprotein, the product of the MDR1 gene, is the most important predictor of an
      adverse clinical course in human patients with osteosarcoma. Exposure of canine
      osteosarcoma cells to doxorubicin resulted in overexpression of MDR1 mRNA and P
      glycoprotein. Furthermore, these cells failed to accumulate doxorubicin
      intracellularly and were less sensitive to vincristine-induced cytotoxicity as
      compared to parental cells.

PMID- 9585066
TI  - Augmentation of anti-tumor effects of methotrexate by distilled water on Dunn
      osteosarcoma in mouse air pouch.
AB  - The anti-tumor effects of hypoosmotic solution of MTX in distilled water (DW) on
      Dunn osteosarcoma were evaluated in mouse air pouches. Dunn osteosarcoma cell
      suspension (1 x 10[5] cells in 0.1 ml of medium) was inoculated into the mouse
      subcutaneous air pouch that had formed 7 days after the initial injection of air.
      Two hours after the inoculation of tumor cells, 5 ml of various concentrations of
      MTX (from 0 to 1 x 10[-3] M) dissolved in DW or PBS were injected into the air
      pouch. Five minutes later, the entire solution in the air pouch was aspirated.
      The mice were sacrificed 3 weeks after the inoculation of tumor cells and the air
      pouch tissue was transected in the coronal plane with the largest area of tumor
      mass. The sections were stained with H&E and the area was measured with the NIH
      Image program. The largest area of tumor mass in the air pouch treated with 1 x
      10(-3) M of MTX in DW was 11.8+/-3.4 mm2 (N = 5), which was significantly (P <
      0.005) smaller than that in PBS (51.7+/-8.3 mm2). These findings suggested that
      hypoosmotic solution in DW might augment the anti-tumor effect of MTX on sarcoma
      cells.

PMID- 9585067
TI  - Inhibitory effect of Hibiscus protocatechuic acid on tumor promotion in mouse
      skin.
AB  - Hibiscus protocatechuic acid (PCA), a phenolic acid isolated from Hibiscus
      sabdariffa L., was evaluated for its ability to inhibit the 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced promotion in skin tumors of female
      CD-1 mice. Topical application of PCA (5, 10 or 20 micromol) 5 min prior to TPA
      (15 nmol) treatment twice weekly for 20 weeks to mice which were initiated with
      benzo[a]pyrene (B[a]P) inhibited the incidence of tumors in mice to 81.3, 62.5
      and 56.3%, respectively, while all mice in the TPA-treated group developed
      tumors. The average number of tumors in mice pretreated with PCA was 2-4 and that
      of mice treated only with TPA was 6.6. The protection effects of PCA were also
      presented by its significant suppression on the TPA-induced hyperplasia in the
      skin and edema of mouse ears by 65 and 73% at doses of 10 and 20 micromol,
      respectively. When it was applied to the dorsal surface of CD-1 mice before TPA
      application, PCA (5, 10 or 20 micromol) inhibited the induction of epidermal
      ornithine decarboxylase (ODC) activity by 5 nmol TPA and myeloperoxidase (MPO)
      activity by 6.5 nmol TPA. The same doses of PCA also reduced the formation of
      hydrogen peroxide in the mouse skin to an inhibition of 61, 84 and 89%,
      respectively, when compared with that of the TPA-treated group. These results
      indicate that PCA possesses potential as a cancer chemopreventive agent against
      tumor promotion.

PMID- 9585068
TI  - Loss of Rb expression in an ACTH-secreting pituitary carcinoma.
AB  - Little is known about the molecular mechanisms of tumor progression in the
      pituitary. However, animal studies suggest that the Rb gene may be involved in
      the development of pituitary carcinoma. Pathologic examination of a pituitary
      tumor that included both benign and malignant components provided insight into
      this mechanism. Both benign and malignant tumors were immunoreactive for ACTH.
      The benign adenoma showed strong nuclear immunoreactivity for Rb, however, both
      the adjacent sellar carcinoma and its metastases were Rb-negative. This study
      suggests that loss of Rb may in some cases be important in the progression of
      pituitary adenoma to carcinoma.

PMID- 9585069
TI  - Serum concentration of hepatocyte growth factor in patients with metastatic
      breast cancer.
AB  - The serum concentration of hepatocyte growth factor (HGF) was examined in 34
      patients with metastatic breast cancer. Although no significant difference was
      observed between HGF concentration and the site of metastasis, serum HGF levels
      were slightly higher in patients with liver metastasis and in patients with
      multiple metastatic sites than in patients with other lesions. Significantly
      higher levels of serum HGF were observed in patients with progressive metastasis
      of breast cancer compared with those with stable metastasis. The patients with
      high HGF levels exhibited a significantly shorter survival rate than those with
      low HGF levels. Circulating HGF levels may be a useful indicator for the
      progression of metastatic lesions and the prognosis of patients with metastatic
      breast cancer.

PMID- 9585070
TI  - Potent growth-suppressive activity of a serine protease inhibitor, ONO-3403,
      toward malignant human neuroblastoma cell lines.
AB  - FOY-305 is a synthetic serine protease inhibitor and ONO-3403 and FO-349 are its
      derivatives. The effects of these compounds on the proliferation of 13 human
      neuroblastoma cell lines were investigated in vitro by MTT colorimetric assay.
      The half maximum inhibition concentrations of ONO-3403 varied between 22 and 90
      microg/ml while those of FOY-305 and FO-349 were higher than 100 microg/ml. ONO
      3403 showed higher growth-inhibitory activity for N-myc-amplified neuroblastomas
      as compared with that for non-amplified cells. Since N-myc amplification in
      neuroblastomas is well correlated with a poor prognosis, ONO-3403 could be an
      effective anticancer drug for malignant neuroblastomas.

PMID- 9585071
TI  - Differential expression of the polyspecific drug transporter OCT1 in rat
      hepatocarcinoma cells.
AB  - The polyspecific drug transporter OCT1 is a plasma transmembrane protein involved
      in the uptake of cationic drugs into hepatocytes. In order to determine whether
      hepatic OCT1 levels, like those of the other cationic drug transporter P
      glycoprotein, may be altered during hepatocarcinogenesis, we have investigated
      OCT1 expression and activity in rat liver carcinoma cells. Similar levels of OCT1
      mRNAs were evident in both normal liver and diethylnitrosamine-induced
      hepatocarcinomas by Northern blot analysis. In contrast, five hepatoma cell lines
      (Fao, Faza, H5, HTC and RHC1) showed either a decrease or an absence of OCT1
      expression compared to normal hepatocytes; these hepatoma cells also displayed
      lower intracellular accumulation of tetraethylammonium (TEA), a well-known
      substrate for OCT1. However, among the hepatoma cell lines, the well
      differentiated Fao cell line was found to retain substantial levels of OCT1
      expression and of intracellular TEA uptake. Therefore, these data provide the
      first evidence that OCT1 expression is well-preserved in chemically-induced rat
      malignant neoplastic liver lesions, whereas it is either decreased or
      undetectable in hepatoma cell lines, which may be related to the loss of various
      liver functions usually occurring in these cell lines.

PMID- 9585072
TI  - Multiprotein reactions in mammalian DNA replication.

PMID- 9585073
TI  - Treatment with low-dose oral etoposide in patients with myelodysplastic
      syndromes.
AB  - Forty-three patients with myelodysplastic syndromes (MDS) received treatment with
      oral etoposide 50 mg/day for 21 consecutive days every 4 weeks. Eighteen patients
      (42%) experienced hematological responses, including 12 of 17 (70%) patients with
      chronic myelomonocytic leukemia (CMML). Three of five CMML patients who failed
      treatment with hydroxyurea experienced major hematological responses with oral
      etoposide. Median response duration exceeded 9 months (range: 4-49 + months), and
      one patient remains in an unmaintained complete remission for 4 years. Toxicity
      included nausea/vomiting in five patients, fever (four patients), infection
      (three patients), mucositis (two patients), and anorexia (two patients). Two
      patients had grade 4 neutropenia with sepsis necessitating treatment withdrawal.
      We conclude that low-dose oral etoposide has remitting activity in MDS and is an
      effective treatment alternative for patients with CMML.

PMID- 9585074
TI  - Phenotypic and genotypic analyses of blastic cell population suggest that pure B
      lymphoblastic leukemia may arise from myelodysplastic syndrome.
AB  - The case history of a 70-year-old man with myelodysplastic syndrome terminated
      into acute leukemia in 22 months is presented. The leukemic cells exhibited
      multifocal acid phosphatase positivity and expressed TdT, CD45, CD34 and HLA-DR
      but not myeloid, monocytic or megakaryocytic differentiation antigenes. The
      genotypic analysis revealed clonal immunoglobulin heavy chain gene rearrangement.
      These phenotypic and genotypic analyses of the blastic cell population suggest
      that myelodysplastic syndrome may transform to pure acute lymphoblastic leukemia
      of B-cell origin.

PMID- 9585075
TI  - Quality of life--an overdue clinical measurement in multiple myeloma.

PMID- 9585076
TI  - Differences in CD14 and alpha-naphthyl acetate esterase positivity and relation
      to prognosis in AML.
AB  - Alpha-naphthyl acetate esterase (ANAE) and CD14 expression, used for
      determination of monocytic cells, were compared and related to prognosis in 65
      AML patients. Bone marrow aspiration material from AML patients has been used for
      the cytochemistry as well as flow cytometry. All non-erythroid cells have been
      included in the evaluation in both methods. 17/65 cases showed at least 15%
      difference between the proportion CD14 and ANAE positive cells. Cases with 20% or
      more CD14 positivity had poorer prognosis. For FAB classes M0-M3, presence of 10%
      or more CD14 was negative for overall survival (P = 0.01). ANAE did not show
      significant prognostic influence.

PMID- 9585077
TI  - Clinical significance of granulocyte colony-stimulating factor (G-CSF) receptor
      expression in acute myeloid leukemia.
AB  - We examined granulocyte colony-stimulating factor (G-CSF) receptor (GR)
      expression on leukemic cells from 44 adults with newly-diagnosed acute myeloid
      leukemia (AML). GR expression was higher in female patients. G-CSF was
      administered to AML patients after initial induction therapy without significant
      acceleration of leukemia, irrespective of GR expression level. G-CSF
      administration after initial chemotherapy did not adversely influence clinical
      outcome of GR-positive patients. However, at first relapse, leukemia regrowth was
      accelerated in 3 of 15 GR-positive patients who received G-CSF after re
      induction. It remains to be determined whether leukemia acceleration due to G-CSF
      contributes to re-induction failure and if G-CSF therapy is a significant risk in
      relapsed, GR-positive AML patients.

PMID- 9585078
TI  - Levels of expression of CAF7 (CD98) have prognostic significance in adult acute
      leukemia.
AB  - The levels of CD98 antigen expression were studied in 62 consecutive cases of
      adult acute leukemia including 24 acute lymphoblastic leukemia (ALL) and 38 acute
      myeloid leukemia (AML) using the monoclonal antibody CAF7 and flow cytometry. The
      mean follow-up was 13.5 months. The mean relative fluorescence intensity (MIF) of
      CAF7 varied between 6 and 83 channels (256 channels resolution). No correlation
      was established between CAF7 cell surface density and most of the predictive
      parameters such as age, sex, blood counts, immunophenotype, proliferative index
      (PI) or DNA index. Nevertheless expression of CAF7 correlated positively with
      survival duration (mean 210 vs 391 days, P = 0.048) and complete remission (CR)
      duration (mean 132 vs 361, days P = 0.032). The levels of CAF7 differed
      significantly between ALL and AML (P < 0.001), the ALL cases being all
      CAF7intermediate or CAF7high. In the AML group the low levels of CAF7 expression
      correlated with shorter CR duration (mean 132 vs 414 days, P = 0.017). The lack
      of correlation with other clinical and biological parameters suggested that CAF7
      might have an independent prognostic significance in adult AML. Although PI was
      also positively related to survival duration (P = 0.02), it did not correlate
      with CR duration or the expression of CAF7. We suppose that the prognostic impact
      of CD98 is related to the control of cell growth and survival in which the
      molecule normally participates.

PMID- 9585079
TI  - MK-886, a leukotriene biosynthesis inhibitor, induces antiproliferative effects
      and apoptosis in HL-60 cells.
AB  - MK-886, a specific inhibitor of 5-lipoxygenase inhibited DNA replication in
      leukemic HL-60 cells in a dose-dependent manner. Addition of exogenous
      leukotriene B4 reversed this effect, whereas addition of leukotriene B4 failed to
      modulate a prostaglandin D2-induced inhibition of DNA replication. The reversal
      of MK-886-induced inhibition was not observed with leukotriene C4. These results
      suggest that the effect of MK-886 is mediated by inhibition of leukotriene B4
      biosynthesis. Moreover, MK-886 not only impaired DNA replication in HL-60 cells
      but also decreased cell proliferation and induced apoptotic cell death. Our
      results suggest a crucial role of leukotriene B4 in the regulation of cell
      proliferation and cell survival in HL-60 cells.

PMID- 9585080
TI  - Enhancement of J6-1 human leukemic cell proliferation by membrane-bound M-CSF
      through a cell-cell contact mechanism II. Role of an M-CSF receptor-like membrane
      protein.
AB  - We have isolated an M-CSF-like membrane-associated growth factor from human
      leukemic J6-1 cells that can enhance the growth and colony formation of J6-1
      cells in vitro. Indirect evidence suggests that this membrane-associated M-CSF
      like growth factor may do so by stimulating a corresponding receptor co-expressed
      on the adjacent J6-1 cells. The objective of this study is to isolate the
      putative receptor in J6-1 cells by virtue of its ability to bind and thus "block"
      the growth of J6-1 cells. Based on this approach, we have isolated from the J6-1
      cell membrane an inhibitory activity that can inhibit the clonal growth of J6-1
      cells. The activity of this inhibitor can be readily neutralized by either anti-M
      CSFR MAb or anti-M-CSFR antiserum, suggesting that it is related to M-CSFR, a
      product of c-fms proto-oncogene. Judging from Sephadex G-200 gel filtration, the
      molecular weight (MW) of this putative M-CSFR-like inhibitor was estimated to be
      approx. 150-180 kDa, comparable with that of M-CSFR. The specificity of M-CSFR
      like protein to recognize and block membrane-bound M-CSF also was implicated by
      its ability to upregulate the steady-state levels of c-fms mRNA in J6-1 cells.
      Besides its antiproliferative activity in vitro, treatment of J6-1 cells with the
      putative receptor protein before inoculation effectively blocked the growth and
      tumor formation in vivo by J6-1 cells in a nude mouse model. These findings
      suggest that the growth and tumor development by J6-1 leukemic cells may involve
      a contact-mediated "juxtacrine mechanism".

PMID- 9585081
TI  - Expression of beta1-integrins and pseudo-immunoglobulins on acute promyelocytic
      leukemia cells and its modifications during in vitro differentiation.
AB  - Adhesion molecules are involved in cell-cell interactions and therefore probably
      play a role in the differentiation and egress of cells from the bone marrow,
      which might be potentially important in the biology of acute promyelocytic
      leukemia (APL). All-trans retinoic acid (ATRA) is known to induce in vitro and in
      vivo differentiation of APL cells and to favor their release from the bone marrow
      into the blood at initiation of therapy. In order to determine whether these
      effects might be mediated in part by modifications of beta1-integrin and
      pseudoimmunoglobulin expression on APL cells, the expression of these adhesion
      molecules on bone marrow (BM) blast cells from 24 APL patients was assayed at
      diagnosis by an indirect immunofluorescence method. CD49b, CD49d, CD49e, CD49f,
      CD54, CD58, and CD56 were expressed respectively on 18%+/-20% (0-66%), 40%+/-31%
      (0-96%), 48%+/-32% (0-97%), 29%+29% (1-94%), 51%+/-30% (5-98%), 37%+/-24% (1-85%)
      and 32%+/-31% (0-97%) of APL cells, with respectively 39%, 71%, 79%, 50%, 70%,
      70%, and 53% positive cases (> or = 20% positive cells). Despite a wide
      variability between individual samples, the expression of beta1-integrins and
      that of pseudo-immunoglobulins tended to be higher in APL in comparison with that
      of a cohort of 63 patients with other AML subtypes with significant differences
      for CD54 expression (51%+/-30% vs 28%+/-27%, P=0.006) and CD56 expression (37%+/
      24% vs 17%+/-19%, P=0.0003). An in vitro differentiation assay was performed in
      nine cases. Cells were harvested after 4-7 days of culture and studied for the
      expression of adhesion molecules. Granulocytic differentiation was marked by
      persistence of CD15 expression. Antigen expression was decreased after culture
      with ATRA for all beta1-integrins (except CD49b and CD49f) and
      pseudoimmunoglobulins (except CD54) tested. However, changes were statistically
      significant only for CD56 (P=0.04), CD49d (P=0.02) and CD49e (P=0.01). The
      modifications in the expression of the beta1-integrins and pseudo immunoglobulins
      were not specific to ATRA-induced differentiation, but commonly observed with
      differentiation. Furthermore, the modifications in the adhesive properties of APL
      cells to extracellular matrix proteins, observed on adhesion assays, were not
      statistically significant after ATRA-induced differentiation. Overall, the level
      of expression of beta1-integrins and pseudo-immunoglobulins was higher in APL
      than in other AML subtypes, and appeared modified with induced differentiation.
      This was not specific of ATRA, but might be involved in the general
      differentiation phenomenon. The modulation of adhesion molecules does not seem a
      sufficient requisite for the development of the retinoic acid syndrome, but could
      nevertheless be part of the increase in leukocyte counts observed during the
      first days of ATRA therapy.

PMID- 9585082
TI  - 1Alpha,25-dihydroxyvitamin D3 and phorbol ester mediate the expression of
      alkaline phosphatase in NB4 acute promyelocytic leukemia cells.
AB  - Both 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and phorbol 12-myristate 13
      acetate [PMA] are cytodifferentiation agents regulating myeloid cell line
      differentiation along the monocyte/macrophage pathway. Alkaline phosphatase (ALP)
      activity has been reported to be absent or present at low levels in
      monocytes/macrophages. In the present study, the acute promyelocytic leukemia
      cell line (NB4) was found to undergo monocyte/macrophage differentiation and
      strongly express ALP activity after exposure to the combination of
      1alpha,25(OH)2D3 and PMA treatment. The ALP stimulation was both dose- and time
      dependent with the ED50 doses for 1alpha,25(OH)2D3 and PMA at 2 x 10(-10) M and 4
      x 10(-11) M, respectively. Assessment of the cell morphology via cell adherence,
      phagocytosis and ALP staining confirmed that NB4 cells treated by
      1alpha,25(OH)2D3 plus PMA showed macrophage characteristics, but were also
      strongly stained with ALP. The present study is the first report that NB4 cells
      express ALP activity as a consequence of combination treatment with
      1alpha,25(OH)2D3 and PMA.

PMID- 9585083
TI  - Detection of BCR-ABL transcripts in acute lymphoblastic leukemia in Indian
      patients.
AB  - Thirty-three patients with acute lymphoblastic leukemia (ALL) from India were
      studied for the presence of BCR-ABL chimeric transcripts, by a seminested cDNA
      PCR. We report the presence of BCR-ABL chimeric transcripts in 4/17 (24%)
      children (under 15 years) and 3/16 (19%) adults (15-50 years). This is in sharp
      contrast to the published literature from the West where the presence of BCR-ABL
      has been reported in only 2-5% children and 35% adults. Whether the presence of
      BCR-ABL fusion mRNA, which is generally an attribute of ALL in adults and of
      poorer prognosis, may contribute to chemo-incurability in young Indian patients,
      remains to be seen, as a larger number of patients are studied for treatment
      outcome and survival on uniform therapy protocols.

PMID- 9585084
TI  - BCL-2 expression does not not correlate with patient outcome in pediatric acute
      myelogenous leukemia.
AB  - Although the Bcl-2 protein inhibits apoptosis (programmed cell death) of lymphoid
      cells induced by a variety of stimuli, its effects on myeloid cell short- and
      long-term survival after chemotherapy are less defined. We sought to elucidate
      the short- and long-term effect of Bcl-2 in a well-studied myeloid cell line (HL
      60) treated with specific anti-AML chemotherapy. HL-60 cells overexpressing Bcl-2
      (HL-60/BCL-2) were more resistant than parental HL-60 cells to multiple
      chemotherapeutic agents in short-term apoptosis and viability assays.
      Significantly, HL-60/BCL-2 cells retained greater long-term proliferative
      capacity than HL-60 cells when treated with low doses of doxorubicin. To assess
      the importance of Bcl-2 expression in pediatric AML we correlated clinical
      outcome and levels of Bcl-2 protein in 22 patient specimens. The correlation did
      not achieve statistical significance with patient response to chemotherapy or
      long-term outcome, suggesting that analysis of larger numbers of patient samples
      would not be useful. Our study suggests that although Bcl-2 clearly promotes
      short and long-term survival in a myeloid cell line, measurement of Bcl-2 levels
      alone are not sufficient to be of prognostic significance in pediatric AML.

PMID- 9585085
TI  - Molecular control of the LDL receptor gene in leukemic cells.

PMID- 9585086
TI  - Increasing incidence of myelodysplastic syndromes: real or fictitious?
AB  - Over the past 10-20 years, there has been a growing interest in the
      myelodysplastic syndromes (MDS). Due to difficulties of diagnosis, classification
      and case recording, the epidemiological features of MDS are still poorly defined.
      Recently, a number of cancer registries have published data on the regional
      occurrence of MDS, suggesting that MDS are much more common than previously
      thought. The crude incidence of MDS in these studies was 3.5-12.6 per 100,000
      population per year. In people over the age of 70 years, incidence rates varied
      between 15 and 50 per 100,000 per year. Contrary to the assumption of most
      hematologists, cancer surveys usually failed to demonstrate a rising incidence of
      MDS. In those studies showing a significant increase in MDS, the rising number of
      cases was probably due to increased physician awareness and extended use of
      invasive diagnostic procedures in elderly people. Differences in incidence
      figures between regional studies may be attributed to several causes, including
      regional variations in disease incidence, small and ill-defined reference
      populations, bias due to patient referral patterns, varying intensity of
      diagnostic procedures and different observation periods. Because of the paucity
      of clinical symptoms and insignificance of morphological bone marrow changes
      particularly in early stage MDS, the currently available incidence figures are
      likely to underestimate the true incidence of MDS. Large-scale epidemiological
      studies are required for obtaining truly representative statistics on the
      incidence and prevalence of the MDS. In industrialized countries, a dramatic
      increase in these disorders can be expected over the next few decades due to the
      'greying' of the population.

PMID- 9585087
TI  - Metabolism and toxicity of diisopropylnaphthalene as compared to naphthalene and
      monoalkyl naphthalenes: a minireview.
AB  - Detailed knowledge does exist on the toxicological safety of
      diisopropylnaphthalene (DIPN). Its metabolism is the key to understanding its
      very low toxicity. The metabolic pathway of 2,6-DIPN in rats was found to proceed
      almost exclusively through oxidation of the isopropyl side-chain. This has
      decisive toxicological implications, which could be demonstrated by comparing the
      lung-specific toxic effects of naphthalenes in mouse: the lack of ring oxidation
      correlates well with lack of lung toxicity while, vice versa, the extent of
      enzymatic oxidative attack at the aromatic ring structure results in a toxic
      pattern that is observed with naphthalene and its monomethyl derivatives. It is
      concluded that DIPN and other highly alkylated naphthalenes are supposed to offer
      favourable safety properties because of their 'alkyl character' and therefore
      must not be compared with the toxic properties of naphthalene and closely related
      aromatic compounds.

PMID- 9585089
TI  - Decreased hepatobiliary secretion of inorganic mercury, its deposition and
      toxicity in the Eisai hyperbilirubinemic rat with no hepatic canalicular organic
      anion transporter.
AB  - Eisai hyperbilirubinemic (EHB) rats, a new mutant strain inbred from Sprague
      Dawley (SD) rats, show no inherent expression of the canalicular multidrug
      resistance protein (cMrp) and lack canalicular multispecific organic anion
      transporter (cMOAT) activity. A sample of 203Hg (40 microCi with 40 microg Hg/kg)
      was injected intravenously (i.v.) into four male SD and EHB rats. Biliary
      excretion of reduced-glutathione (GSH) was 426 and 2 microg/bile for 15 min in
      the SD and EHB rats, respectively. Biliary excretion of 203Hg for 45 min in EHB
      rats significantly decreased to 1/4 of that of the SD rats. However, there was no
      difference in the hepatic uptake of 203Hg between the two strains. Other rats
      were injected subcutaneously (s.c.) with HgCl2 solution (at 0.2 and 1.6 mg/kg)
      containing 203Hg. Some 4 days after the injection of 0.2 mg/kg, about 3 and 13%
      of the total dose was found in the liver in SD and EHB rats, respectively. The
      hepatic supernatant Hg was recovered mainly in the void volume of a Sephadex
      column. Some 2 days after the injection of 1.6 mg/kg, these values were 3 and 23%
      in SD and EHB rats, respectively. The increased retention stimulated hepatic
      metallothionein (MT) induction and increased the proportion of Hg in the MT
      region on the Sephadex column. On the other hand, biliary excretion of 203Hg for
      15 min in EHB rats was about 1/6-1/4 of that in SD rats. With the injection of
      1.6 mg/kg, hepatic and renal functions worsened in EHB rats. In particular,
      severe necrosis was found in the renal tubules. Our results suggest that biliary
      secretion of inorganic Hg may be partly regulated by the ATP-dependent transport
      system, the glutathione S-conjugate export pump (GS-X pump) composed of Mrp and
      MOAT. Significantly decreased excretion stimulates hepatic retention of inorganic
      Hg. However, the hepatic lesions are less predictive. The MT induction may reduce
      the toxicity of metal to the liver cells.

PMID- 9585088
TI  - Altered zinc metabolism contributes to the developmental toxicity of 2
      ethylhexanoic acid, 2-ethylhexanol and valproic acid.
AB  - It has been hypothesized that the developmental toxicity of certain compounds is,
      in part, due to maternal toxicity resulting in alterations in zinc (Zn)
      metabolism that affects the developing conceptus. In the present work the effects
      of developmentally toxic doses of 2-ethylhexanoic acid (EHXA), 2-ethylhexanol
      (EHXO), and valproic acid (VPA) on Zn metabolism were investigated in the
      pregnant rat. In experiment 1, dams were intubated with EHXA (3.13, 6.25, 9.38 or
      12.5 mmol/kg), EHXO (6.25, 9.38 or 12.5 mmol/kg), VPA (1.56, 3.13, 6.25 or 9.38
      mmol/kg), or corn oil (control; 1.0 ml/kg) at 14:00 h on gestation day (GD) 11.5,
      intubated with 32 microCi 65Zn at 22:00 h, and then killed at 08:00 h on GD 12.5.
      At the higher dose levels of EHXA and EHXO, and at all dosages of VPA, the
      percentage of 65Zn retained in maternal liver was higher, while that in the
      embryos was lower, than in controls. Chemical-associated changes in 65Zn
      distribution were associated with increased maternal liver metallothionein (MT)
      concentrations. In experiment 2, dams were fed diets containing 1, 25 or 97
      microg Zn/g from GD 0-16 and intubated with 3.5 mmol EHXA or 1.0 ml corn oil/kg/d
      from GD 8-15. Dams were killed on GD 16 or 19. High incidences of encephalocele
      and tail defects were noted in the GD 16 fetuses of EHXA-treated dams fed either
      the low or adequate Zn diet, the highest incidences being in the low Zn group. On
      GD 19 the incidence of tail defects tended to be higher in the EHXA groups than
      in oil-treated controls, the highest incidence occurring in the low Zn EHXA
      group. Encephalocele was only observed in the low Zn EHXA-treated group. Fetal
      weight and crown-rump lengths were decreased by EHXA treatment and low dietary
      Zn. The incidence of rib anomalies was higher in the EHXA-exposed groups than in
      their respective oil controls. In experiment 3, GD 10.5 embryos collected from
      control dams were cultured for 48 h in serum from control or EHXA-treated male
      rats fed 4.5 or 25.0 microg Zn/g diets. Embryos cultured in either EHXA or low Zn
      sera exhibited delayed development; the addition of Zn to these sera eliminated
      their developmental toxicity. These results support the hypothesis that certain
      chemicals which induce maternal toxicity act, in part, to influence embryonic Zn
      metabolism and trigger abnormal development. Importantly, the teratogenic effects
      of these chemicals can be modulated by dietary Zn intake.

PMID- 9585090
TI  - Cutaneous tolerance to nitroxide free radicals and nitrone spin traps in the
      guinea pig.
AB  - The attempts to use nitroxide free radicals and nitrone spin traps topically in
      skin requires analysis of their potential cutaneous adverse effects. The
      objective of this study was to investigate the skin irritation and sensitizing
      potential of nitroxides and nitrones in the guinea pig. The following
      unsubstituted nitroxides were investigated: 2,2,6,6-tetramethyl-1-piperidinoxyl
      (Tempo), 2,2, 5,5-tetramethyl-3-oxazolidinoxyl (Doxo), 2,2,5,5-tetramethyl-1
      dihydro-pyrrolinoxyl (Proxo), 2,2,3,4,5,5-hexamethyl-imidazoline-1-yloxyl
      (Imidazo) and the nitrones: 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and N-tert.
      butyl-phenylnitrone (PBN). Cutaneous irritation was determined following the
      modified Draize protocol. The response was evaluated clinically as well as by a
      biophysical method analyzing transepidermal water loss (TEWL). The nitroxides and
      nitrones were classified clinically from non-irritant (Proxo, Imidazo, DMPO) to
      slightly irritant (Tempo, Doxo, PBN) according to the Draize protocol. In
      agreement with the clinical scoring, the TEWL values were significantly increased
      by Tempo, Doxo and PBN. TOLH, the hydroxylamine of Tempo and its major skin
      metabolite, did not cause skin irritation. The sensitizing effect was evaluated
      according to the Magnusson and Kligman test. The results showed no cutaneous
      hypersensitivity to all nitroxides and nitrones, indicating a weak sensitizing
      potential. That concludes that the nitroxides and nitrones tested in this study
      have a low potential of acute skin intolerance.

PMID- 9585091
TI  - Augmentation of allergic reactions by several pesticides.
AB  - The augmentative effects of several pesticides on histamine release from mast
      cells of rats that had been sensitized passively by anti-dinitrophenol (DNP)
      monoclonal IgE antibodies were investigated in vitro. Various pesticides,
      especially phenthoate (PAP), chlornitrofen (CNP) and paraquat (PQ), increased
      histamine release. This increase was not observed in histamine release with non
      antigen or induction by calcium ionophore A23187 or compound 48/80. Passive
      cutaneous anaphylaxis (PCA) was examined, and an increase of PCA was observed
      with PAP and PQ, but not with CNP, while an increase of tumor necrosis factor
      alpha (TNF-alpha) production was observed with CNP and PQ, but not PAP. These
      results suggest that various pesticides as environmental pollutants exacerbate
      allergic diseases.

PMID- 9585092
TI  - Gamma-glutamylcysteinylethyl ester attenuates progression of carbon tetrachloride
      induced acute liver injury in mice.
AB  - We examined the effect of gamma-glutamylcysteinylethyl ester (gamma-GCE), which
      is readily transported into hepatocytes and increases hepatocellular reduced
      glutathione (GSH) levels, on the progression of carbon tetrachloride (CCl4)
      induced liver injury in mice in comparison with that of GSH. Administration of
      more than 160 micromol/kg of gamma-GCE, but not GSH, to mice at 3 h after
      intraperitoneal injection of CCl4 (1 ml/kg) significantly attenuated increases in
      serum aspartate aminotransferase and alanine aminotransferase activities at 24 h
      after the CCl4 injection. Increases in hepatic lipid peroxide (LPO)
      concentrations and decreases in hepatic GSH concentrations after the CCl4
      injection were significantly diminished by the gamma-GCE (160 micromol/kg)
      administration, but not by the same dose of GSH. Gamma-GCE, gamma
      glutamylcysteine, and cysteine acted as substrates for glutathione peroxidases
      much less efficiently than GSH in the post-mitochondrial fraction of normal mouse
      liver cells. These results indicate that gamma-GCE attenuates the progression of
      CCl4-induced acute liver injury in mice through the maintenance of hepatic GSH
      levels, leading to inhibition of hepatic LPO formation, which could be due to an
      efficient utilization of GSH converted from gamma-GCE in the liver cells.

PMID- 9585093
TI  - Effect of the peroxisome proliferator ciprofibrate on hepatic cyclooxygenase and
      phospholipase A2 in rats.
AB  - Peroxisome proliferators, which include several hypolipidemic drugs, plasticizers
      and other chemicals, induce hepatic tumors in rodents. These chemicals alter the
      expression of enzymes involved in lipid metabolism, such as the cytochrome P450
      4A family and peroxisomal beta-oxidation enzymes. Previous studies have shown
      that the peroxisome proliferator ciprofibrate reduces eicosanoid concentrations
      in rat livers and primary hepatocyte cultures, yet the mechanism is still
      unclear. In this study we examined cyclooxygenases 1 and 2 (COX-1 and COX-2) and
      cytosolic phospholipase A2 (cPLA2) to determine whether the rate-limiting enzymes
      in the eicosanoid synthetic pathway are altered by ciprofibrate. Rats were fed
      0.01% ciprofibrate for 3, 6, or 10 days. Western analysis revealed that COX-2
      protein was induced by ciprofibrate (up to 13-fold at day 10), but that calcium
      dependent (Ca-D) cPLA2 protein was not different from controls. The enzyme
      activity of calcium-independent (Ca-I) cPLA2 in ciprofibrate-treated rats was
      increased 2-fold, whereas Ca-D cPLA2 and total COX activities were not affected.
      Using enzyme kinetics, we found that COX-1 (Ki = 143 microM) and Ca-I cPLA2 (Ki =
      121 microM) were competitively inhibited by ciprofibrate, but the inhibition was
      not physiologically significant. COX-2 and Ca-D cPLA2 were not inhibited by
      ciprofibrate. These results show that ciprofibrate increases Ca-I cPLA2 enzyme
      activity and COX-2 protein expression.

PMID- 9585094
TI  - The guinea-pig skin sensitization test revisited: an evaluation formula to
      predict possible sensitization levels for eight chemicals used in household
      products.
AB  - In predicting human skin sensitization due to possible risky chemicals, it is not
      sufficient to evaluate solely the minimum induction dose (MID) or the standard
      challenge dose (SCD) in the Guinea Pig Maximization Test (GPMT). Nakamura et al.
      (1994) (Nakamura, A., Momma, J., Sekiguchi, H., Noda, T., Yamano, T., Kaniwa, M.,
      Kojima, S., Tsuda, M., Kurokawa, Y., 1994. A new protocol and criteria for
      quantitative determination of sensitization potencies of chemicals by guinea pig
      maximization test. Contact Dermatitis 31, 72-85) previously measured the residual
      dose of chemicals in the products implicated in human allergic accidents, and
      stated that '... the level of chemical in the products (direct exposure-dose =
      DED) was similar to or higher than value of sensitization potency.' However,
      several of the chemicals listed in their article, show an even lower value of
      sensitization potency than the DED, although a potential correlation between
      results of the GPMT and the DED was seemed to be evident; a key question about
      the essential rule of those parameters therefore remains open. Using the data of
      Nakamura et al. (1994), we analyzed the functional rules of the three independent
      parameters, the MID, the SCD, and the DED on which the GPMT is based.
      Calculations of the degree of allergic reactions elicited in humans provided a
      range of discrimination constants (D) using the formula; D = DED/(MID*SCD).
      Possible human allergic accidents may be predicted when the dose of a candidate
      chemical in a chemical product (equal to DED) exceeds the value; D*(MID*SCD),
      following the correct evaluation of the MID as well as the SCD.

PMID- 9585095
TI  - Mixed effects of 2,6-dithiopurine against cyclophosphamide mediated bladder and
      lung toxicity in mice.
AB  - 2,6-Dithiopurine (DTP) has been proposed as a possible chemopreventive agent
      because of its ability to react with electrophiles. Acrolein, an electrophilic
      metabolite of cyclophosphamide (CP) involved in the toxicities of this anticancer
      drug, can be scavenged by DTP. The present study examined the effect of DTP
      treatment on CP-mediated bladder and lung toxicity in male ICR mice. Mice fed a
      diet containing 4% DTP that were treated intraperitoneally (i.p.) with 350 mg/kg
      CP showed no significant bladder damage (measured as bladder blood content at 48
      h) with respect to the group fed a control diet. DTP (50 and 100 mg/kg), given
      i.p. 0.5 and 7 h after the initial injection of CP, also prevented the bladder
      damage when compared with the group receiving CP alone. Surprisingly, although
      neither parenteral CP nor DTP alone caused any mortality at these doses, the
      combined treatment resulted in 67% mortality within 3 days. At 24 h after CP +
      DTP, blood urea nitrogen was elevated 6-fold and urine volumes decreased by 70%.
      Histopathological analyses revealed a diffuse myocardial degeneration and
      necrosis, severe granular degeneration in the liver, abundant cellularity and
      infiltrates in interalveolar spaces in the lung and swollen nephron epithelial
      cells with some necrosis. All mice survived treatment when the dose of CP was
      lowered to 250 and 25-75 mg/kg DTP was given i.p. 0.5 and 7 h after CP. These DTP
      regimens reduced the degree of CP-induced lung toxicity, measured by
      [3H]thymidine incorporation into lung DNA 7 days after CP, in a dose-dependent
      manner. DTP (75 mg/kg) also reduced CP-induced lung fibrosis estimated by lung
      hydroxyproline content 28 days after CP. Analyses of urine from mice given CP +
      DTP revealed large amounts of the metabolic product dithiouric acid, smaller
      amounts of the parent DTP and several smaller peaks. The major unique metabolite
      peak was collected and analyzed by mass spectrometry, but did not correspond to
      either acrolein-DTP or acrolein-dithiouric acid. Thus, either very small amounts
      of an acrolein adduct are generated, the adduct is broken down to an unidentified
      product, or the ability of DTP to prevent CP-induced lung and bladder damage is
      related to some other mechanism. The possibility that mercapturic acid
      metabolites of acrolein released the parent electrophile in the urine was not
      supported by the finding that probenecid did not prevent CP-induced bladder
      toxicity.

PMID- 9585096
TI  - Rat brain acetylcholinesterase activity: developmental profile and maturational
      sensitivity to carbamate and organophosphorus inhibitors.
AB  - A growing body of evidence indicates that young animals exhibit an increased
      susceptibility to the lethal effects of cholinesterase (ChE)-inhibiting
      insecticides. Our laboratory is engaged in defining factors which may explain
      this age-related sensitivity. This report includes results from experiments
      designed to compare the developmental profiles, kinetic parameters and intrinsic
      (i.e. in vitro) sensitivity of developing male rat brain acetylcholinesterase
      (AChE) activity to carbamate and organophosphorus anticholinesterases. Total ChE
      activity in whole brain for each age was composed of about 90% AChE and 10%
      butyrylcholinesterase (BuChE) activity for the six ages examined. Brain AChE
      activity showed an age-related increase in Vmax until postnatal day 17 with no
      change in Km (average of all six ages approximately equal to 72 microM). Optimal
      substrate (acetylthiocholine) concentration for each age was 1 mM, and there was
      substrate inhibition (approximately 10%) at 2.5 mM. IC50s (the concentration of
      compound that inhibits 50% of the AChE activity in 30 min at 26 degrees C)
      defined concomitantly for postnatal day 4 and adult brain AChE using either
      aldicarb, carbaryl, chlorpyrifos-oxon or malaoxon were virtually identical at
      both ages with average IC50 values being: aldicarb = 2.4 microM, carbaryl = 1.7
      microM, chlorpyrifos-oxon = 4.9 nM and malaoxon = 140 nM. In summary, AChE in
      young and adult brain differs mostly in specific activity while the Km(s),
      substrate profiles, and in vitro sensitivity to selected anticholinesterase
      insecticides are not different. Therefore, these data support the hypothesis that
      the greater sensitivity of the young animals to anticholinesterase pesticides is
      not due to the greater sensitivity of the target molecule AChE to these
      inhibitors.

PMID- 9585097
TI  - Ozone affects breathing and pulmonary surfactant function in mice.
AB  - The effect on breathing of BALB/c mice immediately following ozone exposure (2
      ppm) for 0, 2, 4, 6, and 8 h was studied with a whole body plethysmograph.
      Whether such exposure affected the normal function of pulmonary surfactant of
      maintaining airway patency was evaluated with a capillary surfactometer.
      Respiratory rate in mice that were not exposed was 358+/-16 (mean+/-S.E.)
      breaths/min and decreased to 202+/-10 after 6 h exposure. The mean pressure
      change caused by breathing diminished significantly, indicating a reduced tidal
      volume. BAL fluid from controls maintained patency for 88+/-2% of the study time,
      120 s, implying a good surfactant function, but the ozone exposure caused the
      surfactant to lose its capability of maintaining patency (P < 0.0001). This
      decaying surfactant function of the BAL fluid coincided with an increasing
      protein concentration in the fluid of exposed animals (1.46+/-0.14 mg/ml in the 8
      h group) as compared to controls (0.44+/-0.04 mg/ml, P < 0.0001). It is concluded
      that leakage of plasma proteins into the airway lumen was probably the main
      reason for the surfactant dysfunction, which may have contributed to the altered
      breathing pattern.

PMID- 9585098
TI  - Molecular modelling and quantitative structure-activity relationship studies on
      the interaction of omeprazole with cytochrome P450 isozymes.
AB  - Molecular modelling of the anti-ulcerative agent, omeprazole, with the putative
      active sites of cytochromes P4503A4 and P4502C19, enzymes which are the major
      catalysts of omeprazole metabolism in man, are reported. Interactive docking of
      omeprazole in both CYP3A4 and CYP2C19 gives rise to binding orientations which
      are consistent with both the known sites of metabolism reported for these
      isoforms and with evidence from site-directed mutagenesis experiments on CYP2C19,
      a P450 associated with genetic polymorphism in human drug metabolism. The
      potential P450 enzymic interactions, inhibition and induction of omeprazole are
      discussed in the light of molecular modelling and QSAR (quantitative structure
      activity relationship) studies on related compounds.

PMID- 9585099
TI  - In vivo and in vitro evaluation of the mutagenic potential of carbamazepine: does
      melatonin have anti-mutagenic activity?
AB  - The mutagenic potential of carbamazepine (CBZ) therapy has been evaluated both in
      vivo and in vitro. Analysis of chromosome aberrations (CA), sister chromatid
      exchanges (SCEs), mitotic and proliferation indices (PRI) were performed. The in
      vivo study was carried out on 30 patients with idiopathic epilepsy end undergoing
      treatment with CBZ for different periods starting from 6 months up to 15 years.
      Plasma CBZ levels were also determined for each patient. The results showed that
      the total CA and SCEs were significantly increased in CBZ-treated patients. There
      was no significant correlation between CA and either duration of treatment or the
      plasma CBZ levels for each patient. The mitotic and proliferation indices were
      found to be slightly but non-significantly decreased compared to control values.
      On the other hand, in vitro analysis showed a significant dose-dependent increase
      in CA and SCEs in human lymphocyte cultures treated with CBZ (4-12 microg/ml).
      The mitotic and proliferation indices were also found to be decreased but only
      significantly in case of high doses of CBZ (12 microg/ml). Pretreatment of human
      lymphocytes with melatonin (0.5 mM) exhibited a significant decrease in the
      frequencies of CBZ-induced CA and SCEs as compared with non-treated cultures. The
      depressed mitotic and proliferation indices were also found to be improved in
      cultures pretreated with melatonin. In conclusion, these observations suggest
      that CBZ monotherapy may lead to chromosome damaging effects (genotoxic) and the
      use of melatonin as anti-mutagenic agent for human protection against CBZ-induced
      chromosome damage should be considered.

PMID- 9585100
TI  - Evaluation of the potential immunotoxicity of chlorinated drinking water in mice.
AB  - Recent epidemiological studies have reported associations between the consumption
      of chlorinated drinking water and various types of human cancer; in addition,
      exposure to chlorine (Cl-) in drinking water has been reported to suppress
      certain immune functions in laboratory animals. The current studies were
      conducted to extend our knowledge of the effects of drinking water exposure to Cl
      . Female C57BL/6 mice were administered hyperchlorinated drinking water (7.5, 15,
      or 30 ppm Cl-) for 2 weeks prior to sacrifice for evaluation of spleen and thymus
      weights, the plaque-forming cell (PFC) response, hemagglutination (HA) titer, and
      lymphocyte proliferation (LP). Significant reductions in organ weights and immune
      response were observed in the positive control groups (i.e. dexamethasone- or
      cyclophosphamide-exposed mice). No consistent differences were observed between
      the Cl--exposed animals and vehicle control mice for the evaluated parameters.
      Thus, under the conditions of these experiments, 2 weeks of exposure to
      hyperchlorinated drinking water had no apparent adverse effects on immune
      function.

PMID- 9585101
TI  - Does airway responsiveness increase after skin sensitisation to 3-carene: a study
      in isolated guinea pig lungs.
AB  - Guinea pigs were sensitised by dermal exposure to 3-carene according to the
      modified cumulative contact enhancement test (CCET) protocol. Lungs from
      sensitised and non-sensitised animals were then perfused with buffer and exposed
      for a period of 10 min to two different air concentrations of 3-carene, 600 and
      3000 mg/m3. 3-Carene caused a statistically significant bronchoconstriction even
      at the relatively low concentration of 600 mg/m3 and the constriction was dose
      dependent. 600 mg/m3 of 3-carene caused a reduction of 19% in conductance
      capacity and 16% in compliance capacity. 3000 mg/m3 of 3-carene decreased lung
      compliance and conductance by 43 and 31%, respectively. The lungs from sensitised
      animals tended to show a greater response than lungs obtained from control
      animals. The lower concentration of 3-carene is close to and may even be below,
      occupational limit values in Sweden, Germany and USA.

PMID- 9585102
TI  - Cypermethrin-induced alteration of thymocyte distribution and functions in
      prenatally-exposed rats.
AB  - The synthetic pyrethroid insecticide, cypermethrin (50 mg/kg) was given during
      gestation to pregnant rats by gavage in corn oil. Prenatal cypermethrin exposure
      induced a significant decrease in the absolute number of all thymocyte subsets
      during the first 30 days after birth, being the double negative CD4-CD8-, single
      positive CD4 and CD8 T cells preferentially affected. Later on day 60 and 90
      double positive CD4+CD8+ and single positive thymocytes gradually recovered,
      while the total number of CD4 CD8 cells was increased. Moreover, thymocytes from
      rats prenatally exposed to cypermethrin showed an impaired ability to proliferate
      in response to different doses of Concanavalin A (ConA) and human recombinant
      interleukin-2 (hrIL-2) and to produce and/or release IL-2. Overall, our results
      indicate that cypermethrin administered during prenatal period can affect
      multiple steps in thymocyte differentiation pathways resulting in an altered cell
      subset distribution and an impairment of thymocyte functions.

PMID- 9585103
TI  - Serotonin and vasoconstrictor synergism.
AB  - Contractile synergism between serotonin (5-hydroxytryptamine, 5-HT) and other
      vasoconstrictor substances has been observed in a number of peripheral and
      cerebrovascular blood vessels. This phenomenon may play an important role in
      certain pathological states such as hypertension, peripheral vascular disease,
      and coronary spasm. In the present review, we summarize studies on the synergism
      between serotonin and other vasoconstrictor agents and focus on a recently
      described type of vasoconstrictor synergism in which precontraction with a non-5
      HT receptor agonist yields an enhanced contractile response to serotonin which is
      mediated by previously inactive or "silent" 5-HT receptor subtypes.

PMID- 9585104
TI  - Effect of human and murine interferon-alpha on steroid production by rat ovarian
      cells.
AB  - The effect of interferon on the rat ovarian cell function was investigated. Cells
      from the ovary of juvenile rats were used as a model to investigate the effect of
      IFN-alpha on the secretion of estradiol and testosterone. In addition the effect
      of human IFN-alpha (hIFN-alpha) on the secretion of testosterone by the rat adult
      testis was studied. Present results show that leukocyte hIFN-alpha decreased the
      human chorionic gonadotropin (hCG) stimulated secretion of estradiol and
      testosterone by ovarian cells, and the production of testosterone by testis
      cells. Basal secretion of steroids was affected later and in less proportion than
      the hCG-dependent production. The IFN-alpha obtained from murine leukocytes, also
      inhibited the response of ovarian cells to the hCG stimulus.The nature of this
      effect in the secretion of the steroids is dose and time-dependent. The
      incubation of hIFN-alpha with an specific antibody completely blocked the effect
      of the cytokine on ovarian cells.

PMID- 9585105
TI  - Cyclosporin A-induced hydrogen peroxide synthesis by cultured human mesangial
      cells is blocked by exogenous antioxidants.
AB  - Cyclosporin A (CsA) is the immunosupressor most widely used in transplanted
      patients for preventing organ rejection, but it has some toxic side effects in
      vascular beds and kidney. The purpose of this work was to study if H2O2, a
      reactive oxygen species, is involved in the CsA-induced toxic effects on kidney
      in vitro. Human mesangial cells (HMC) in culture were incubated in presence of
      CsA (10[-5]-10[-8]M) and H2O2 was measured by flow cytometry. The specificity of
      the probe used in this method was demonstrated as fluorescence was not detected
      when superoxide anion generated through a Xanthine-Xanthine oxidase system was
      present, but fluorescence was noted when H2O2 was present in the incubation
      medium, both directly and after addition of superoxide dismutase to the medium
      thus promoting H2O2 synthesis. CsA induced a significant dose and time-response
      increased H2O2 synthesis by cultured HMC. This increase appeared 5 min after CsA
      addition, being maximal between 15-45 min at CsA concentration of 10(-7)M. When
      HMC were preincubated with antioxidants as vitamin E or selenium, the CsA-induced
      H2O2 production was partially blocked. In addition, selenium also induced an
      increased activity of glutathion peroxidase in HMC after 24 hours of incubation,
      suggesting that it exerted its H2O2 scavenging action through the modulation of
      the activity of this enzyme.

PMID- 9585106
TI  - Protective effect of prazosin on the hydrogen peroxide-induced derangements in
      the isolated perfused rat heart.
AB  - The effect of prazosin, an alpha1-selective adrenoceptor antagonist, on the
      hydrogen peroxide (H2O2)-induced mechanical and metabolic derangements was
      studied in the isolated rat heart, which was perfused aerobically by the
      Langendorffs technique at a constant flow rate and driven electrically. H2O2 (600
      microM) produced both mechanical dysfunction (e.g., increase in the left
      ventricular end-diastolic pressure) and metabolic damage (e.g., decrease in the
      level of adenosine triphosphate) associated with lipid peroxidation (e.g.,
      increase in the level of malondialdehyde). The H2O2-induced mechanical and
      metabolic derangements were attenuated by 2.5, 5, or 10 microM prazosin, and the
      increase in the level of malondialdehyde was attenuated by 5 or 10 microM
      prazosin. Nevertheless, prazosin had practically no effects on the mechanical
      function and energy metabolism of the H2O2-untreated normal heart at 2.5 or 5
      microM, although it reduced the mechanical function at 10 microM. Prazosin was
      shown to have a hydroxyl radical scavenging effect. These results suggest that
      prazosin attenuates the H2O2-induced mechanical and metabolic derangements
      probably because of attenuation of the H2O2-induced lipid peroxidation in the
      heart.

PMID- 9585107
TI  - Inhibitory action of spinorphin, an endogenous regulator of enkephalin-degrading
      enzymes, on carrageenan-induced polymorphonuclear neutrophil accumulation in
      mouse air-pouches.
AB  - Whether spinorphin, an endogenous regulator of enkephalin-degrading enzymes,
      plays a role in an anti-inflammatory action was examined, using a mouse air-pouch
      assay as a model of acute inflammation. Repeated intravenous administration (6
      times) of spinorphin every hour significantly suppressed carrageenan-induced
      polymorphonuclear neutrophil (PMN) accumulation, an indicator of inflammation
      (3.21+/-0.95 x 10[6] cells vs 8.92+/-0.96 x 10[6] cells, 10mg/kg spinorphin
      treated vs saline-treated group, n=5, P<0.01) at 6 hr. The combination of
      spinorphin and leuhistin (2 mg/kg, i.v.), a specific inhibitor of aminopeptidase
      N (APN), markedly suppressed the PMN accumulation induced by carrageenan (1.11+/
      0.17 x 10[6] cells, 88% inhibition compared to the saline-treated group, n=5,
      P<0.01). This inhibition was less than, but comparable to that of dexamethasone
      (30 mg/kg/one shot, i. v.), a representative anti-inflammatory drug. These
      results indicate that spinorphin may be an endogenous anti-inflammatory
      regulator, its inhibitory activity being modulated by APN.

PMID- 9585108
TI  - Ibuprofen inhibits leukocyte migration through endothelial cell monolayers.
AB  - During inflammation leukocytes are playing a tremendous role in the defense
      against bacterial infections. Tumor necrosis factor alpha (TNF alpha) increases
      adhesion of leukocytes to endothelial cells. The non steroidal anti-inflammatory
      drug ibuprofen is able to reduce inflammatory processes in humans and is a widely
      used drug. The influence of ibuprofen on TNF-alpha-induced expression of adhesion
      molecules on endothelial cells is well investigated and has been published
      recently by our group. For leukocyte migration, leukocytes have to attach and
      finally migrate through monolayers of endothelial cells. The aim of the current
      study was to investigate leukocyte migration through endothelial cell monolayers
      (ECM) under ibuprofen using a migration assay system. Ibuprofen was identified as
      a potent inhibitor of the leukocyte migration through endothelial cell monolayers
      in a dose dependent manner. The treatment of either leukocytes (87 +/- 17.6 %;
      p>0.05) or endothelial cell monolayers (62.5 +/- 9.4 %; p<0.05) showed that the
      influence is more mediated through endothelial cells, the treatment of both cell
      types demonstrated an additive effect. In conclusion, the previously published
      changes of adhesion molecules on endothelial cells could be confirmed with this
      functional migration test. The inhibition of the leukocyte migration may
      contribute to the anti-inflammatory actions of the drug.

PMID- 9585109
TI  - A local immuno-endocrine interaction may mediate rat adrenal glucocorticoid
      response to bacterial endotoxins.
AB  - The effects of the bacterial endotoxin lipopolysaccharide (LPS) and interleukin
      (IL)-1beta on corticosterone secretion has been studied in vivo by employing the
      technique of in situ perfusion of the isolated rat left adrenal gland. Both LPS
      and IL-1beta dose-dependently raised corticosterone output, the response peaking
      at 60 and 90 min, respectively. IL-1 receptor antagonist dose-dependently
      reversed the effect of LPS and IL-1beta. The IL-1beta converting enzyme (ICE)
      inhibitor Ac-YVAD-CMK annulled the adrenal response to LPS, but did not affect
      that to IL-1beta. Collectively, these findings provide evidence that LPS, by
      enhancing adrenal production of IL-1beta, is able to evoke a sizable
      glucocorticoid response in the rat, thereby suggesting that local immuno
      endocrine interactions may be operative in the adrenal gland of this species.

PMID- 9585111
TI  - Alpha1-adrenergic and dopaminergic receptors are involved in the anoretic effect
      of corticotropin-releasing factor in goldfish.
AB  - This study investigates the noradrenergic and/or dopaminergic receptors subtypes
      involved in the anoretic action of CRF in goldfish. Agonists and antagonists of
      alpha1- and alpha2-adrenoceptors, and D1- and D2-dopaminergic receptors were
      intracerebroventricularly (i.c.v.) administered alone or in combination with CRF
      in the case of antagonists. Food intake and hypothalamic content of
      catecholamines and their metabolites were measured at 2 h postinjection. On one
      hand, alpha1-adrenergic receptor antagonist, but not alpha2, blocked the anoretic
      effect of CRF. Moreover, we found a blockade of CRF-induced anoretic action by
      pretreatment with specific D1- and D2-dopaminergic antagonists. On the other
      hand, the i.c.v. administration of CRF reduced hypothalamic norepinephrine (NE)
      and dopamine (DA) content, without modifications in their metabolism. Thus, our
      results suggest that the anoretic effect of CRF appears to be mediated by alpha1
      adrenergic and dopaminergic receptors in fish. Second, the reduction in
      hypothalamic NE and DA synthesis could be due to a direct effect of CRF treatment
      and/or a secondary effect of food intake reduction.

PMID- 9585110
TI  - The response of lung epithelium to well characterised fine particles.
AB  - Diesel particles form a large component of the fine particle fraction (PM10) in
      urban air in the UK. During pollution episodes small increases in PM10 have been
      linked to detrimental health effects. The comparative toxicological effects of
      diesel exhaust and other well-characterised particles (carbon black, amorphous
      and crystalline silica) on rat respiratory epithelium were investigated in the
      present study. The effects of small masses of particles (1 mg) delivered by
      intratracheal instillation were monitored by changes in components of lavage
      fluid. Respirable, crystalline quartz, produced significant increases in lung
      permeability, persistent surface inflammation, progressive increases in pulmonary
      surfactant and activities of epithelial marker enzymes up to 12 weeks after
      primary exposure. Ultrafine amorphous silica did not induce progressive effects
      but it promoted initial epithelial damage with permeability changes and these
      regressed with time after exposure. By contrast, ultrafine/fine carbon black had
      little, if any, effect on lung permeability, epithelial markers or inflammation,
      despite being given at a dose which readily translocated the epithelium and which
      has been reported to induce inflammation. Similarly, diesel exhaust particles
      produced only minimal changes in lavage components, although they were smaller
      individual particles and differed in surface chemistry from carbon black. It is
      concluded that diesel exhaust particles are less damaging to respiratory
      epithelium than silicon dioxide and that the surface chemistry of a particle is
      more important than ultrafine size in explaining its biological reactivity.

PMID- 9585112
TI  - Identification of a distinct molecular mass G alpha(h) (transglutaminase II)
      coupled to alpha1-adrenoceptor in mouse heart.
AB  - Our previous studies on alpha1-adrenoceptor signaling suggested that G alpha(h)
      family is a signal mediator in different species. To elucidate the species
      specificity of G alpha(h) family in molecular mass, we used the solubilized
      membranes from mouse heart and the ternary complex preparations containing alpha1
      agonist/receptor/G-protein. Binding of [35S]GTPgammaS and the intensity of the
      [alpha-32P]GTP photoaffinity labeled protein resulting from activation of the
      alpha1-adrenoceptor were significantly attenuated by the antagonist,
      phentolamine. The molecular mass of the specific GTP-binding protein was
      approximately 72-kDa; homologous with G alpha(h) (transglutaminase II) family.
      Furthermore, immunological cross-reactivity of ternary complex from mouse heart
      and purified G alpha(h) from rat, guinea pig, and bovine using anti-G alpha(h7)
      antibody showed that their molecular masses were distinctly different and
      approximately 72-kDa G alpha(h) from mouse heart was the lowest molecular mass.
      Consistent with these observations, in co-immunoprecipitation and co
      immunoadsorption of the alpha1-adrenoceptor in the ternary complex preparation by
      anti-G alpha(h7) antibody, the G alpha(h) family protein tightly coupled to
      alpha1-adrenoceptor. These results demonstrate the species-specificity of G
      alpha(h) family in molecular mass, especially the lowest molecular mass in mouse.

PMID- 9585113
TI  - Effect of antioxidant in endothelial cells exposed to oxidized low-density
      lipoproteins.
AB  - Antioxidants such as probucol and alpha-tocopherol have been shown to attenuate
      the oxidation of low-density lipoproteins (LDL) and atherosclerotic lesions in
      animal models of atherosclerosis. The purpose of this study is to determine the
      protection effect of antioxidants on endothelial cells when exposed to oxidized
      and native LDL. In a cell-free system, we found that probucol, alpha-tocopherol,
      and ascorbic acid inhibited copper-induced LDL oxidation by a dose-dependent
      fashion (from 1 microM to 10 mM). In porcine aortic endothelial cells,
      antioxidants alone did not change basal endothelin-1 (ET-1) secretion. When
      porcine aortic endothelial cells were exposed to LDL and oxidized-LDL, both of
      them stimulated ET-1 secretion dose-dependently, whereas oxidized-LDL elicited
      higher ET-1 secretion. However, probucol, alpha-tocopherol, and ascorbic acid did
      not prevent LDL or oxidized-LDL induced ET-1 secretion. Furthermore, nimodipine
      inhibited both of native and oxidized LDL induced ET-1 secretion. Since Ca2+
      channel blocker reduced the elevation of induced ET-1 secretion, the [Ca2+]i is
      possibly involved for the regulation of ET-1 secretion. Our results suggest that
      antioxidants can only prevent the oxidation of LDL rather than oxidized and
      native LDL-induced ET-1 secretion in vascular endothelial cells. The increase in
      the [Ca2+]i of endothelial cells through the opening of voltage-dependent Ca2+
      channels may be involved in the LDL-induced ET-1 release.

PMID- 9585114
TI  - Effects of CD-832, a new calcium antagonist, on intracranial pressure in
      anesthetized dogs.
AB  - Effects of a new calcium antagonist, CD-832, on intracranial pressure (ICP),
      vertebral blood flow (VBF) and common carotid blood flow (CCBF) were investigated
      in dogs and the results were compared with findings for nifedipine and diltiaem.
      Dogs were anesthetized with sodium pentobarbital and a 20-gauge needle was
      inserted into the cisterna magna for ICP determination. Mean arterial blood
      pressure (MBP), heart rate (HR), CP, VBF and CCBF were measured before and during
      the continuous intravenous infusion of CD-832 (0.3, 1 and 3 microg/kg/min),
      nifedipine (0.1, 0.3 and 1 microg/kg/min) or diltiazem (1, 3 and 10
      microg/kg/min). Although the three drugs caused a comparable hypotension,
      differences were evident in effects of these agents on ICP, VBF and CCBF.
      Nifedipine and diltiazem but not CD-832 significantly increased ICP, VBF and
      CCBF. These results suggest that CD-832 is a unique calcium antagonist which does
      not increase ICP during hypotension. Because the most evident side effects of
      calcium antagonists are caused by vasodilation and include headache and flushing,
      CD-832 may possibly be useful to treat subjects with hypertension or angina
      pectoris.

PMID- 9585116
TI  - An update on the CNS actions of TRH and its analogs.
AB  - This brief review will discuss the recent literature on several of the central
      actions of TRH and its analogs. The most prominent of these actions include: (1)
      the arousal or analeptic effect in drug narcotized animals or in concussion
      models; (2) the reversal of cognitive deficits produced by various drugs or
      procedures, and (3) the improvement of several neurological deficits produced in
      animal models of spinal and/or cerebellar injury. The mediation of these TRH
      effects by neurotransmitters is discussed. While little has been published on the
      human neuropsychopharmacology of TRH, and especially of its analogs, the future
      holds considerable therapeutic promise for these interesting drugs.

PMID- 9585115
TI  - Fenamates inhibit contraction of guinea-pig isolated bronchus in vitro
      independent of prostanoid synthesis inhibition.
AB  - The inhibitory and relaxant effects of flufenamic and tolfenamic acids on guinea
      pig isolated bronchus were compared with those of verapamil and indomethacin.
      Flufenamic and tolfenamic acids (each drug, 20 microM) and verapamil (1 microM)
      inhibited bronchial contraction induced by Ca2+, KCl or PGF2alpha whereas
      indomethacin (20 microM) had no inhibitory effect. Only verapamil, but not
      flufenamic and tolfenamic acids and indomethacin, inhibited methacholine-induced
      contraction. Flufenamic and tolfenamic acids and verapamil (each drug, 0.1-33
      microM) relaxed the bronchus precontracted by KCl or PGF2alpha. In contrast,
      indomethacin (0.1-33 microM) did not relax KCl- or PGF2alpha-precontracted
      bronchus. Verapamil, but not flufenamic and tolfenamic acids and indomethacin,
      relaxed methacholine precontracted bronchus. In conclusion, fenamates inhibit
      Ca2+-, KCl- and PGF2alpha-induced contractions in guinea-pig isolated bronchus in
      a manner involving inhibition of Ca2+ influx but not inhibition of prostanoid
      synthesis.

PMID- 9585117
TI  - Role of alpha1-adrenoceptor subtypes in production of the positive inotropic
      effects in mammalian myocardium: implications for the alpha1-adrenoceptor subtype
      distribution.
AB  - Both alpha1A- and alpha1B-adrenoceptor subtypes are present in mammalian
      myocardium. Alpha1-adrenoceptor activation can enhance myocardial contractility,
      and two possible inotropic mechanisms are proposed: an increase in myofilament
      Ca2+ sensitivity and an increase in transsarcolemmal Ca2+ influx during action
      potential prolongation that accompanies the transient outward current inhibition.
      We suggest that the former is mediated by the alpha1B-adrenoceptor subtype and
      the latter is by the alpha1A-adrenoceptor subtype. The alpha1B-adrenoceptor
      subtype may be located on a space more proximal to the sympathetic nerve endings
      than the alpha1A-adrenoceptor subtype, because the positive inotropic effect of
      endogenous norepinephrine was mediated entirely by the alpha1B-adrenoceptor
      subtype. In some species, the sustained positive inotropic effect develops
      following the transient negative inotropic effect, which is mediated by the
      alpha1A-adrenoceptor subtype.

PMID- 9585118
TI  - Alpha-adrenoceptor subtypes of dog saphenous vein: another unusual property.
AB  - The functional relationship between vascular smooth muscle alpha1- and alpha2
      adrenoceptor (AR) subtypes was investigated by simultaneous measurement of
      contractile and fluorescence ratio in fura-2 loaded rings of dog saphenous vein
      (DSV). Prazosin, as well as rauwolscine, at 0.1 microM, substantially antagonized
      contractions and associated cytosolic [Ca2+] rises induced by UK 14304, while
      rauwolscine, as well as prazosin, antagonized similar effects of phenylephrine
      (PE). These antagonisms were characterized by a parallel rightward shift of the
      concentration-response curves. In the absence of extracellular Ca2+, PE as well
      as UK 14304 caused simultaneous transient elevation of contractile force and
      cytosolic [Ca2+], although the UK 14304 responses were smaller than PE responses.
      We propose that DSV smooth muscle cells possess interacting alpha1- and alpha2
      ARs which have overlapping functional domain sensitive to the agonists and
      antagonists of either alpha-AR subtype. Both alpha-AR subtypes appear to utilize
      similar signaling mechanisms via Ca2+ release from the same intracellular stores
      and Ca2+ entry across the plasma membrane.

PMID- 9585120
TI  - Differential down-regulation of alpha-2 adrenergic receptor subtypes.
AB  - The regulation of G protein-coupled receptor expression is important in the
      physiology of an organism and can occur at any of the steps between gene
      transcription to turnover of the receptor protein itself. Agonist stimulation
      causes receptor desensitization, which is characterized by a rapid reduction in
      response to the agonist. Down-regulation often occurs after prolonged agonist
      treatment and is manifested as a decrease in receptor density. Short term
      desensitization results from a rapid (in minutes) and reversible uncoupling of
      the receptor-G protein complex, followed by sequestration and/or internalization
      of receptors from the cell surface. Receptors are not degraded as removal of
      agonist rapidly restores receptor function. Down-regulation, on the other hand,
      displays a much longer time-course (hours to days) and is characterized by a
      decrease in receptor density as determined by radioligand binding. Removal of
      agonist will only slowly reverse down-regulation, because new receptor synthesis
      is required in most cases (1;2). The mechanism of receptor down-regulation is not
      well understood, but may include an accelerated rate of removal of receptors, a
      decrease in the rate of appearance of receptors, or both. Our previous studies
      have shown significant differences in the concentration of agonist required to
      produce down-regulation of alpha-2 adrenergic receptor subtypes (3;4). Here we
      review the mechanisms and molecular determinants for receptor down-regulation as
      well as our own data exploring the subtype-specific differences in alpha-2
      receptor down-regulation. We find that the extent and time-course of agonist
      induced down-regulation occurs in a similar fashion regardless of the receptor
      subtype or the cell line in which it is expressed. The mechanism for receptor
      down-regulation in all cases is an increase in the rate of receptor
      disappearance.

PMID- 9585119
TI  - Alpha1-adrenoceptor subtypes and two receptor systems in vascular tissues.
AB  - The subtypes of alpha1-adrenoceptor are coexpressed in many tissues. We examined
      the relationship between coexpressed alpha1-adrenoceptor subtypes and their
      functions in blood vessels. Rat and rabbit aortas coexpressed three subtypes
      (alpha1A, alpha1B, alpha1D) and four subtypes (alpha1A, alpha1B, alpha1D,
      alpha1L), respectively. In rat aorta however, noradrenaline-induced contraction
      was mediated predominantly through the alpha1D subtype, and oxymetazoline
      produced alpha1B-mediated contraction. In rabbit aorta, concentration-response
      curves for noradrenaline were composed of two components (alpha1B and alpha1L
      mediated), while oxymetazoline produced alpha1L-mediated contraction. Therefore,
      the inhibitory actions of some antagonists varied markedly among tissues and
      agonists. These results demonstrate diversity of the two receptor systems and
      suggest that the heterogeneity of physiological responses reflects the
      differences in functional subtypes among tissues and in their sensitivities to
      agonists and antagonists.

PMID- 9585121
TI  - Central distribution and function of 5-HT6 receptor subtype in the rat brain.
AB  - The purpose of the present study was to elucidate the distribution of 5-HT6
      receptor mRNA and possible physiological functions of the 5-HT6 receptor subtype
      using antisense oligonucleotides (AOs) in rats. Continuous
      intracerebroventricular injection of AOs caused a 30% reduction in the number of
      [3H]-lysergic acid diethylamide binding sites. Conditioned fear stress-induced
      increase in 5-HT release from the prefrontal cortex was significantly inhibited
      by treatment with AOs. The present study suggests that 5-HT6 receptors may be
      functionally expressed in the brain, where one of the functions appears to be in
      the mediation of certain anxiety disorders.

PMID- 9585122
TI  - Prostanoid receptor heterogeneity through alternative mRNA splicing.
AB  - Prostaglandin (PG) and thromboxane (TX) receptors are G-protein coupled receptors
      that mediate the physiological actions of the five principal prostanoid
      metabolites: PGD2, PGE2, PGF2alpha, PGI2 (prostacyclin) and TXA2. Five major
      subdivisions of the prostanoid receptor family have been defined
      pharmacologically which correspond to each of the metabolites as follows: DP, EP,
      FP IP and TP. The EP receptors have been further classified pharmacologically
      into the EP1, EP2, EP3 and EP4 subtypes. Molecular biological studies have
      resulted in the cloning of cDNA's encoding all of these prostanoid receptors. In
      addition, the cloning of these receptors has revealed further heterogeneity
      through the use of alternative mRNA splicing. Specifically, mRNA splice variants
      have been identified for the EP1, EP3, FP and TP receptors. Interestingly, except
      for the EP1 receptors, the mechanisms giving rise to these receptor isoforms
      involves the use of splice sites located in the cytoplasmic carboxyl termini of
      these receptors. Thus, the eight human EP3 isoforms that have been identified are
      otherwise identical except for their carboxyl termini. Similarly, the optional
      use of a potential splice site encoding the carboxyl terminus gives rise to each
      of the two FP and TP receptor isoforms. Because the carboxyl termini of G-protein
      coupled receptors are generally implicated in interactions with G-proteins, it is
      not surprising that these receptor isoforms differ mainly with respect to their
      activation of second messenger pathways and not in their pharmacological
      characteristics. Differences also exist with respect to their levels of
      constitutive activity (e.g., in the absence of agonist) and in their
      desensitization.

PMID- 9585123
TI  - Endothelin: receptor subtypes, signal transduction, regulation of Ca2+ transients
      and contractility in rabbit ventricular myocardium.
AB  - Endothelin (ET) isopeptides, ET-1, ET-2 and ET-3, elicit a positive inotropic
      effect (PIE) in association with a negative lusitropic effect, essentially with
      identical efficacies and potencies in the isolated rabbit papillary muscle, but
      with different concentration-dependent properties. Pharmacological analysis
      indicates that the PIE of ET-1 is mediated by an ETA2 subtype that is less
      sensitive to BQ-123 and FR139317, whereas the PIE of ET-3 is mediated by an ETA1
      subtype that is highly sensitive to these ETA antagonists. ETs increased the
      amplitude of intracellular Ca2+ transient (CaT) in indo-1 loaded rabbit
      ventricular myocytes, but the increase was much smaller than that produced by
      elevation of [Ca2+]o or isoproterenol for a given extent of PIE, an indication of
      increased myofibrillar Ca2+ sensitivity. ETs stimulate phosphoinositide (PI)
      hydrolysis, which leads to production of inositol 1,4,5-trisphosphate (IP3) and
      diacylglycerol (DAG). Evidence for the role of IP3-induced Ca2+ release in
      cardiac E-C coupling is tenuous. Generation of IP3 induced by ET-1 was transient
      and returned to the baseline level when the PIE reached an elevated steady level.
      Protein kinase C (PKC) that is activated by DAG and also via other pathways
      triggered by ETs stimulates Na+-H+ exchanger to lead to an increased [Na+]i and
      alkalinization. The former may contribute to an increase in the amplitude of CaT
      through Na+-Ca2+ exchanger, and the latter, to an increase in myofibrillar Ca2+
      sensitivity. A number of PKC inhibitors, such as staurosporine, H-7, calphostin C
      and chelerythrine, consistently and selectively inhibited the PIE of ET-3 without
      affecting the PIE of isoproterenol and Bay k 8644. The maximum inhibition was 20
      30% of the total response. A Na+-H+ exchange inhibitor, [5-(N-ethyl-N-isopropyl)
      amiloride (EIPA)] or a Ca2+ antagonist, verapamil, could not completely inhibit
      the PIE of ET-3, but the combination of both inhibitors totally abolished the PIE
      of ET-3. These findings indicate that activation of PKC and subsequent activation
      of Na+-H+ exchanger and/or L-type Ca2+ channels may play a crucial role in the
      cardiac action of ET isopeptides in the rabbit ventricular myocardium.

PMID- 9585124
TI  - Regulation of inducible NO synthase expression by endothelin in primary cultured
      glial cells.
AB  - Nitric oxide (NO), initially identified as an endothelium-derived relaxing
      factor, is a molecular mediator that has been implicated in many physiological
      and pathological processes. In primary cultured rat glial cells, a combination of
      inflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta)) and bacterial lipopolysaccharide (LPS) stimulates production of
      nitrite via expression of the inducible form of nitric oxide synthase (iNOS). In
      these cells, simultaneous addition of endothelin (ET) markedly inhibited TNF
      alpha/IL-1beta-induced and LPS-induced nitrite production and iNOS expression,
      although ET by itself had no effect. The inhibitory effect of ETs appears to be
      mediated by ET(B) receptors. Forskolin also inhibited the iNOS expression. By
      contrast, pretreatment with ET for 24 hours enhanced LPS-induced nitrite
      production and iNOS expression. This stimulatory effect of ETs was suppressed by
      calphostin C, a protein kinase C inhibitor, and pretreatment with phorbol ester
      enhanced LPS-induced iNOS expression. Our findings present the possibility that
      ET has dual effects on iNOS expression in glial cells.

PMID- 9585125
TI  - Regulation by ARIA/neuregulin of acetylcholine receptor gene transcription at the
      neuromuscular junction.
AB  - Transcription of genes encoding nicotinic acetylcholine receptor (AChR) subunits
      (alpha, beta, gamma or epsilon, and delta) is highest in nuclei localized to the
      synaptic region of the muscle which contributes to maintain a high density of
      AChRs at the postjunctional membrane. ARIA (AChR inducing activity) is believed
      to be the trophic factor utilized by motor neurons to stimulate AChR synthesis in
      the subsynaptic area. ARIA stimulates tyrosine phosphorylation of the erbB
      proteins and activates the MAP kinase pathway which is required for the ARIA
      mediated induction of AChR genes.

PMID- 9585126
TI  - Beta3-adrenoceptor mechanisms in guinea-pig taenia caecum.
AB  - Beta-adrenoceptor-mediated relaxation of guinea-pig taenia caecum was
      investigated by studying the effects of BRL37344, CGP12177 and norepinephrine.
      These drugs caused graded relaxation of the guinea-pig taenia caecum. The
      concentration-response curves for these drugs were unaffected by propranolol,
      atenolol, butoxamine, prazosin, yohimbine and phentolamine. Bupranolol produced
      shifts of the concentration-response curves for these drugs. Schild regression
      analyses carried out for bupranolol against BRL37344, CGP12177 and norepinephrine
      gave pA2 values of 5.79, 5.61 and 5.53, respectively. CGP12177 and norepinephrine
      significantly increased cyclic AMP levels in this preparation. Bupranolol
      significantly decreased cyclic AMP levels elicited by CGP12177 and
      norepinephrine, whereas propranolol produced no effect. These results suggest
      that the relaxant responses to BRL37344, CGP12177 and norepinephrine in the
      guinea-pig taenia caecum are mediated by beta3-adrenoceptors.

PMID- 9585127
TI  - Examination of ligand-induced conformational changes in the beta2 adrenergic
      receptor.
AB  - The environmentally sensitive and cysteine reactive fluorescent probe, IANBD, was
      used to monitor ligand-induced structural changes in the beta2 adrenergic
      receptor (beta2AR) by fluorescent spectroscopy. We found that agonists caused a
      dose-dependent and reversible decrease in fluorescence from the purified IANBD
      labeled beta2AR. This suggested that agonists promote a conformational change in
      the receptor that leads to an increase in the polarity of the environment around
      one or more IANBD labeled cysteines. The wildtype receptor contains eight free
      cysteines and mutagenesis and peptide mapping experiments have indicated that
      several of these sites are accessible for chemical derivatization. Thus, to
      identify the cysteine(s) involved in the agonist-induced change in fluorescence
      and thereby map agonist-induced conformational changes in the beta2AR, we
      generated a series of mutant receptors having limited numbers of cysteines
      available for fluorescent labeling. Fluorescence spectroscopy analysis of the
      purified and site-selectively IANBD-labeled mutants showed that IANBD labeled
      125Cys and 285Cys are responsible for the observed changes in fluorescence
      consistent with movements of TM III and VI in response to agonist binding.

PMID- 9585128
TI  - Domains of beta1 and beta2 adrenergic receptors to bind subtype selective
      agonists.
AB  - We studied the binding region of several beta1 and beta2 selective agonists by
      using chimeric beta1 and beta2ARs, and point-mutated beta2 adrenergic receptors
      (ARs). By replacing a single transmembrane domain (TMD) of beta1AR (or beta2AR)
      with the corresponding region of beta2AR (or beta1AR), we found that beta2 or
      beta1 selectivities were determined by TMD2 and TMD7 of beta2AR or by TMD2 of
      beta1AR, respectively. Alanine-substituted beta2AR mutants showed that tyrosine
      at position 308 in TMD7 played an important role in binding of beta2 selective
      agonists with high affinity. These data also suggested that the substituent on
      the amine portion was important for subtype selective agonist binding.

PMID- 9585129
TI  - The structure and function of A1 and A2B adenosine receptors.
AB  - Of the four G protein coupled adenosine receptor (AR) subtypes, the A1 is best
      suited for studies of reconstitution with G proteins. Recombinant A1 receptors
      extended with hexahistidine and FLAG have been purified to near homogeneity. In
      reconstitution assays using pure recombinant G protein subunits, the composition
      of the gamma subunit influences coupling to purified A1ARs. The least well
      characterized AR is the A2B. New data indicate that A(2B)ARs can trigger the
      degranulation of canine and human mast cell lines. Recombinant human A(2B)ARs are
      blocked by the anti-asthma drugs theophylline and enprofylline at concentrations
      that are used therapeutically to treat asthma. Although A(2B)ARs have long been
      known to stimulate adenylyl cyclase, they also can activate phospholipase C and
      mobilize Ca2+ by signaling through Gq/11. There is great potential for new
      therapies based on compounds that selectively target individual AR subtypes.

PMID- 9585130
TI  - Regulation of neurokinin-1 receptor expression by GABA(B) receptor agonists.
AB  - Activation of GABA(B) receptors produces analgesia in acute and chronic pain
      models. Data indicate that a possible mechanism for this effect is a GABA(B)
      receptor-induced blockade of neurokinin-1 (NK-1) receptor gene expression in the
      spinal cord. While much more potent GABA(B) receptor agonists (CGP 44532) have
      been developed, there is no information on their antinociceptive properties or
      their ability to influence NK-1 receptors. To address these issues, rats were
      treated with baclofen or CGP 44532 and tested for sedation, ataxia, and pain
      related behaviors in a chronic pain model (formalin hindpaw injection). In a
      separate group of experiments the analgesic response to a single dose of CGP
      44532 was tested prior, and subsequent to, its chronic administration. The
      results indicate that CGP 44532 is a substantially more potent analgesic than
      baclofen. In addition, after chronic administration baclofen was no longer
      capable of inducing analgesia or of inhibiting the increased expression of NK-1R
      mRNA and CGP 44532 was still fully effective in both regards. The results suggest
      that GABA(B) agonists could be clinically useful analgesics.

PMID- 9585132
TI  - Receptor-mediated and receptor-independent activation of G-proteins in rat brain
      membranes.
AB  - High-affinity GTPase activity intrinsic to G-proteins, which serves as an index
      of G-protein activation elicited through agonist-stimulated receptors as well as
      by receptor-independent direct G-protein activators like mastoparan, was measured
      in rat brain membranes. Receptor-mediated high-affinity GTPase activity was
      detectable preferentially for the Gi subfamily associated with adenylyl cyclase
      inhibition mediated by group II metabotropic glutamate, pirenzepine-insensitive
      muscarinic acetylcholine, GABA(B), adenosine A1, dopamine D2-like (striatum), and
      serotonin 5-HT1A (hippocampus) receptors. The pharmacological characteristics of
      such receptor-mediated high-affinity GTPase activities were presented.
      Mastoparan, a tetradecapeptide from wasp venom which has been shown to directly
      activate Gi and Go, inhibited low-affinity GTP hydrolyzing activity, probably due
      to its activating effect on nucleoside diphosphokinase (NDPK). When NDPK activity
      was inhibited completely by UDP, mastoparan stimulated high-affinity GTPase
      activity in a concentration-dependent manner. There are many compounds other than
      mastoparan with apparently diverse structural properties which have been shown to
      directly activate G-proteins. The relevance and possible participation of
      receptor-independent mode of G-protein activation for some neuropeptides were
      discussed.

PMID- 9585131
TI  - The efficacy of delta-opioid receptor-selective drugs.
AB  - Delta-opioid receptor-selective drugs may provide an alternative to mu-opioid
      selective drugs currently used for the relief of pain. To develop improved delta
      opioid receptor-selective drugs, better measures of drug activity are necessary.
      In this review we suggest that efficacy calculations provide a superior measure
      of drug activity as compared to dissociation constants and drug potencies in
      functional assays. Efficacy, as discussed in this review, is defined as a
      quantitative measurement of the ability of a drug to stimulate second messenger
      systems or measurable functional responses in cells or tissues under standard
      conditions. Efficacy values will allow medicinal chemists to understand the
      contributions of both the coupling efficiency and dissociation constant to drug
      potencies in the development of new delta-opioid receptor-selective drugs.

PMID- 9585133
TI  - Differential regulation of N- and Q-type Ca2+ channels by cyclic nucleotides and
      G-proteins.
AB  - Voltage-dependent Ca2+ channels play a central role in controlling
      neurotransmitter release at the synapse. They can be inhibited by certain G
      protein-coupled receptors, acting by a pathway delimited to the membrane. In
      addition, modulation of Ca2+ channel activity by protein kinases also contributes
      to the dynamic regulation of neuronal physiology. Recently, differences in these
      modulations between Ca2+ channel subtypes have been shown in several neuronal
      preparations. Here we show that two types of presynaptic Ca2+ channel (N-type and
      Q-type) are differentially regulated by cAMP and G-proteins using a Xenopus
      oocyte expression system. Treatment to increase cytosolic cAMP concentration with
      forskolin and 3-isobutyl-1-methylxanthine (IBMX) markedly potentiated Q-type
      channel current, and the enhancement was reversed by protein kinase A inhibitors.
      Much smaller enhancement was observed in N-type channel current after the cAMP
      elevation. When large depolarizing prepulse was applied to the oocytes for
      evaluation of the tonic inhibition of Ca2+ channels by intrinsic G-protein
      activity, N-type channel current elicited a large prepulse facilitation but Q
      type channels did not. The tonic inhibition of N-type channels was abolished by
      an intracellular perfusion with a 'cut-open' recording configuration, or by co
      expression with G(alpha o). When kappa opioid receptors were co-expressed and
      stimulated with agonists, depolarization-resistant inhibition was more apparent
      in Q-type channels than in N-type channels. These results suggest that Q-type
      channels are more susceptible to the protein kinase A-mediated facilitation than
      N-type channels, and that activity of N-type channels can be more highly
      regulated in a voltage-dependent manner by G(betagamma) than that of Q-type
      channels. These differences may account for the selective regulation of
      neurotransmitter release by these Ca2+ channels.

PMID- 9585134
TI  - Molecular diversity and double regulatory mechanism of activation of
      phospholipase C in rat brain.
AB  - Whereas evidence for a G protein-dependent stimulation of phospholipase C (PLC)
      is abundant, reports on the inhibition of PLC through a G protein-mediated
      pathway have only recently begun to appear. In the present study, cerebral cortex
      membranes were chosen since they have a readily measurable Gpp[NH]p and Ca2+
      stimulated PLC activity. Nanomolar concentrations of Gpp[NH]p, a hydrolysis
      resistant GTP analogue, inhibited basal inositol 1,4,5-trisphosphate (IP3)
      production, with a maximum inhibition of 25% at 10 nM. Increasing the
      concentrations of Gpp[NH]p to over 10 nM resulted in a reversal of the inhibitory
      effect and onset of stimulation of IP3 production. GDPbetaS as a G protein
      inhibitor and U-73122 as a putative PLC-beta inhibitor had little effect on basal
      IP3 production at 100 microM and 1 microM, respectively. However, GDPbetaS and U
      73122 completely antagonized both the inhibition and the stimulation of IP3
      production produced by lower and higher concentrations, respectively, of
      Gpp[NH]p. Rat cortical membranes expressed a greater amount of PLC-beta1. These
      data suggest that PLC-beta1 isozymes may be regulated by both inhibitory and
      stimulatory G protein-mediated mechanisms.

PMID- 9585135
TI  - Activation of PI 3-kinase by G protein betagamma subunits.
AB  - We have reported that fMLP-induced activation of pertussis toxin-sensitive GTP
      binding proteins in THP-1 cells potentiates the insulin-induced accumulation of
      PtdIns(3,4,5)P3, a product of phosphoinositide 3-kinase (T. Okada et al.,
      Biochem. J. 317, 475-480, 1996). The synergism in PtdIns(3,4,5)P3 accumulation
      was observed in Chinese hamster ovary cells expressing both insulin and fMLP
      receptors. In rat adipocytes, which represent the physiological target cells of
      insulin, receptor-mediated activation of GTP-binding protein by adenosine and
      prostaglandin E2 potentiated the insulin-induced PtdIns(3,4,5)P3 accumulation. In
      cell-free systems, the activity of the p85/p110beta subtype of phosphoinositide 3
      kinase was, while that of p85/p110alpha was not, stimulated by the betagamma
      subunits of the GTP-binding proteins. We propose here a hypothesis that the
      p85/p110beta subtype is under the control of both the insulin receptors and the
      GTP-binding protein-coupled receptors in intact cell systems.

PMID- 9585136
TI  - Molecular mechanisms of G protein-coupled receptor desensitization and
      resensitization.
AB  - Beta-arrestin proteins play a dual role in regulating G protein-coupled receptor
      (GPCR) responsiveness by contributing to both receptor desensitization and
      internalization. Recently, beta-arrestins were also shown to be critical
      determinants for beta2-adrenergic receptor (beta2AR) resensitization. This was
      demonstrated by overexpressing wild-type beta-arrestins to rescue the
      resensitization-defect of a beta2AR (Y326A) mutant (gain of function) and
      overexpressing a dominant-negative beta-arrestin inhibitor of beta2AR
      sequestration to impair beta2AR dephosphorylation and resensitization (loss of
      function). Moreover, the ability of the beta2AR to resensitize in different cell
      types was shown to be dependent upon beta-arrestin expression levels. To further
      study the mechanisms underlying beta-arrestin function, green fluorescent protein
      was coupled to beta-arrestin2 (beta arr2GFP), thus allowing the real-time
      visualization of the agonist-dependent trafficking of beta-arrestin in living
      cells. Beta arr2GFP translocation from the cytoplasm to the plasma membrane
      proceeded with a time course, sensitivity and specificity that was
      indistinguishable from the most sensitive second messenger readout systems. Beta
      arr2GFP translocation was GRK-dependent and was demonstrated for 16 different
      ligand-activated GPCRs. Because beta-arrestin binding is a common divergent step
      in GPCR signalling, this assay represents a universal methodology for screening
      orphan receptors, GRK inhibitors and novel GPCR ligands. Moreover, beta arr2GFP
      provides a valuable new tool to dissect the biological function and regulation of
      beta-arrestin proteins.

PMID- 9585137
TI  - Subtype-specific differences in subcellular localization and chlorethylclonidine
      inactivation of alpha1-adrenoceptors.
AB  - Chlorethylclonidine (CEC) inactivation has been used as one criterion to
      subclassify the alpha1-adrenoceptors (AR); however, the extent of CEC
      inactivation can vary depending on the CEC treatment. By constructing the FLAG
      tagged (N-terminus) and green fluorescent protein (GFP)-fused (C-terminus) alpha1
      ARs, we have determined the relationship between CEC sensitivity and the cellular
      localization of alpha1-AR subtypes using COS-7 cells. In GFP-expressing cells,
      flow cytometry analysis with anti-FLAG N-terminus antibody detected strong
      fluorescent signals in most of alpha1B-AR-expressing cells, but low signals in
      alpha1A-AR-expressing cells. Further examination with confocal microscopy showed
      that fluorescent signals densely localized intra-cellularly in alpha1A-AR
      expressing cells, while most of alpha1B-AR localized on the cell surface.
      Furthermore, radioligand binding studies with [125I]HEAT showed that CEC (10
      microM) treatment of intact cells inactivated approximately 30-40% of alpha1A-AR
      and >90% of alpha1B-AR, while the CEC treatment of membrane preparations resulted
      in >80% decrease in the alpha1A-AR density and >90% of alpha1B-AR density,
      respectively. The results showed that the hydrophilic alkylating agent CEC
      inactivated only alpha1-AR on the cell surface irrespective of its subtype, and
      that the subtype-specific sorting is a major determinant for CEC inactivation of
      alpha1-AR. Subtype-specific cellular localization suggests a new class of
      functional properties that may explain the signal and functional diversity of
      homologous alpha1-AR (as well as other G protein-coupled receptors) subtypes.

PMID- 9585138
TI  - Recent biochemical studies of the dopamine transporter--a CNS drug target.
AB  - The DAT is an important component of the dopaminergic synapse. It is critical for
      removing dopamine from extracellular space and is a target or "receptor" for
      various drugs. Recent electron microscopic immunocytochemical studies indicate
      that DAT, while found in nerve terminal membranes, has a very low presence (if
      any) in the synapse itself, and is mainly found in perisynaptic areas. Also,
      different levels of DAT are found in different dopaminergic nuclei. These
      findings suggest that diffusion of the transmitter may be more important than
      previously thought. Finally, the turnover rate of the DAT protein is similar to
      other synaptic proteins such as receptors.

PMID- 9585139
TI  - Application of "one-bead one-compound" combinatorial library methods in signal
      transduction research.
AB  - Using a "split-synthesis" solid phase synthetic approach, bead libraries can be
      generated such that each bead displays only one chemical entity. This "one-bead
      one-compound" combinatorial library can then be assayed for specific biological
      properties using either a solid-phase on-bead binding or functional assay, or a
      releasable solution phase assay. Positive compound-beads can then be isolated for
      structure determination. Various assay systems to screen such a "one-bead one
      compound" library are described. We have used this combinatorial library method
      to discover peptides that bind to the cell surface immunoglobulins of murine
      lymphoma cells. Such peptides, when presented in an oligomeric form to a lymphoma
      cell are able to induce signal transduction. Additionally, we have also applied
      the "one-bead one-compound" combinatory library approach to elucidate peptide
      substrate motifs for protein tyrosine kinases. Multiple distinct peptide motifs
      were identified for p60(c-src) protein tyrosine kinase. Using the identified
      peptide substrates as templates, potent and highly specific pseudosubstrate-based
      peptide inhibitors were developed.

PMID- 9585140
TI  - In vivo receptor binding of novel alpha1-adrenoceptor antagonists for treatment
      of benign prostatic hyperplasia.
AB  - New types of alpha1-adrenoceptor antagonists (tamsulosin, KMD-3213 and JTH-601)
      are currently receiving a great deal of attention, especially in terms of
      developing effective therapeutic agents to treat bladder outlet obstruction with
      less side effects, such as postural hypotension, in patients with benign
      prostatic hyperplasia (BPH). In vivo alpha1-adrenoceptor binding properties of
      these antagonists in prostate and other tissues of rats were examined.
      Intravenous injections of tamsulosin, KMD-3213 and JTH-601 inhibited dose
      dependently in vivo specific [3H]tamsulosin binding in various tissues. Ratios of
      ID50(aorta) to ID50(prostate) of KMD-3213 and JTH-601 were greater than those of
      tamsulosin and prazosin. Further, the ratios of ID50(spleen) to ID50(submaxillary
      gland) of these drugs were greater than that of prazosin. Following intravenous
      injections of [3H]KMD-3213 in rats, the amount of specific binding in prostate
      was significantly greater than that of [3H]prazosin, but that in aorta or spleen
      was much smaller. Interestingly, [3H]JTH-601 showed little in vivo specific
      binding in aorta. These data suggest that KMD-3213 and JTH-601 exhibit higher
      affinity to alpha1-adrenoceptors in prostate and submaxillary gland than in
      vascular tissues in vivo.

PMID- 9585141
TI  - Stimulatory effect of paeoniflorin on adenosine A-1 receptors to increase the
      translocation of protein kinase C (PKC) and glucose transporter (GLUT 4) in
      isolated rat white adipocytes.
AB  - In an attempt to understand the subcellular signals after activation of adenosine
      A-1 receptors, paeoniflorin was employed to incubate with rat white adipocytes in
      vitro. Translocation of protein kinase C (PKC) beta-subtype from cytosol to
      membrane was enhanced by an incubation with paeoniflorin in a concentration
      dependent manner similar to that of porcine insulin. Also, 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX) inhibited this action of paeoniflorin in a concentration
      related fashion and it markedly attenuated the action of paeoniflorin at a
      concentrations sufficient to block the action of adenosine. Moreover,
      chelerythrine inhibited the paeoniflorin-stimulated translocation of PKC in a way
      similar to that stimulated by porcine insulin. Subcellular inhibition is
      considered because stimulation of porcine insulin was not modified by DPCPX at
      concentrations sufficient to block adenosine A-1 receptors. Similar results were
      also observed in adipocytes regarding the translocation of glucose transporter
      (GLUT4) from cytosol to membrane. Thus, we found that paeoniflorin can activate
      adenosine A-1 receptors to increase the translocations of PKC and GLUT4, two
      major signals for glucose uptake, from cytosol to membrane of the white
      adipocytes in rats.

PMID- 9585143
TI  - The potential of subtype-selective neuronal nicotinic acetylcholine receptor
      agonists as therapeutic agents.
AB  - Neuronal nicotinic acetylcholine receptors (NAChRs) are pentameric ligand-gated
      ion channel receptors which exist as different functional subunit combinations
      which apparently subserve different physiological functions as indicated by
      molecular biological and pharmacological techniques. It is possible to design and
      synthesize novel compounds that have greater selective affinities and efficacies
      than nicotine for different NAChRs, which should translate into different
      behavioral profiles and therapeutic potentials. Examples of NAChR agonists
      studied are nicotine, SIB-1508Y, SIB-1553A and epibatidine. These compounds have
      different degrees of selectivity for human recombinant NAChRs, different
      neurotransmitter release profiles in vitro and in vivo and differential
      behavioral profiles. Preclinical studies suggest that SIB-1508Y is a candidate
      for the treatment of the motor and cognitive deficits of Parkinson's disease,
      whereas SIB-1553A appears to have potential as a candidate for the treatment of
      Alzheimer's disease. Epibatidine has a strong analgesic profile, however the
      ratio between pharmacological activity and undesirable effects is so low that it
      is difficult to envisage the use of this compound therapeutically. Nicotine has a
      broad profile of pharmacological activity, for instance demonstrating activity in
      models for cognition and analgesia. As for epibatidine, the adverse effects of
      nicotine severely limits its therapeutic use in humans. The discovery of subtype
      selective NAChR agonists such as SIB-1508Y and SIB-1553A provides a new class of
      neuropsychopharmacological agents with better therapeutic ratios than nonspecific
      agents such as nicotine.

PMID- 9585142
TI  - Studies on relationships between chemical structure and beta-blocking potency of
      bopindolol and its two metabolites.
AB  - The structure-activity relationships of bopindolol and its two metabolites (18
      502 and 20-785) and their beta-blocking potencies in the human beta2-adrenoceptor
      (AR) were assessed using molecular modeling on an INDIGO2 workstation (SGI Co.,
      Ltd.) and DISCOVER/INSIGHT II (Biosym Co., Ltd.). Through modeling, possible
      binding sites for these agents were hypothesized to involve the 3rd, 4th, 5th and
      6th helices of the beta2-AR, and these shared a common interaction site at Asp113
      in helix 3. The different chemical structure of these three agents, however,
      showed binding to different binding sites (amino acids). This study therefore
      suggests that different beta-blocking potencies of these agents may be due to
      different chemical structure.

PMID- 9585144
TI  - Targeting disruption of histamine H1 receptors in mice: behavioral and
      neurochemical characterization.
AB  - With gene targeting, one can practically knock out a gene in vivo and create a
      mutant organism that completely lacks the gene product. The mutant mice lacking
      histamine H1 receptors was generated by the method of gene targeting. In brains
      of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. The
      mutant mice showed impaired locomotor activity and exploratory behavior in an
      open field and activity wheel. Behaviors of the mutant mice were examined with
      several other tasks such as passive avoidance test, resident-intruder aggression
      test and formalin test to clarify the role for the H1 receptors in behaviors.
      Behavioral changes observed in the mutant mice are almost compatible with those
      obtained by the classical pharmacological tools. In correlation to the behavioral
      changes in the mutant mice, 5-hydroxytryptamine release was significantly
      increased in the brains of mutant mice.

PMID- 9585145
TI  - GABA(A)-receptor assembly in vivo: lessons from subunit mutant mice.
AB  - The rules governing the assembly of GABA(A) receptors in vivo were assessed in
      subunit mutant mice. The transcription of individual subunit genes was regulated
      independently. The lack of a particular subunit did not result in a molecular
      rescue by an enhanced transcription of other subunits. In addition, the
      availability of an alpha- and beta-subunit was essential for receptor formation.
      Finally, highly selective recognition processes directed the subcellular
      targeting of receptors. The loss of a particular receptor subtype (alpha5) did
      not lead to a subcellular redistribution of the remaining subtype (alpha2)
      present in the same cell.

PMID- 9585146
TI  - Phosphorylation-dependent reversible translocation of Ca2+/calmodulin-dependent
      protein kinase II to the postsynaptic densities.
AB  - The translocation of soluble Ca2+/calmodulin-dependent protein kinase II (CaM
      kinase II) to postsynaptic densities (PSDs) was investigated. When soluble CaM
      kinase II previously autophosphorylated was incubated with PSDs, the kinase was
      precipitated by centrifugation, indicating that the soluble kinase associated
      with PSDs and formed a PSD-CaM kinase II complex. Ca2+-independent activity
      generated by autophosphorylation of the kinase was retained in the complex. A
      number of PSD proteins were phosphorylated by the kinase associated with PSDs in
      both the absence and presence of Ca2+. When PSD-CaM kinase II complex was
      incubated at 30 degrees C, the enzyme was dephosphorylated and released from the
      complex. These results indicate that CaM kinase II reversibly translocates to
      PSDs in a phosphorylation-dependent manner.

PMID- 9585147
TI  - Epidermal growth factor receptor-mediated expression of NF-kappaB transcription
      factor in osteoblastic MC3T3-E1 cells cultured under a low-calcium environment.
AB  - We examined the effect of a low calcium environment on DNA-protein binding
      reaction activity of the transcription factor, NF-kappaB in osteoblastic MC3T3-E1
      cells, using an electrophoretic mobility shift assay. Binding sites for the NF
      kappaB sequence in DNA in nuclear protein in MC3T3-E1 cells are present. This DNA
      protein binding reaction activity increased in MC3T3-E1 cells with EGF treatment,
      compared with those with no treatment. When MC3T3-E1 cells were placed in a low
      calcium environment, DNA-protein binding reaction activity seemed to decrease.
      This suggests that the phosphorylation of IkappaB is less active in a low calcium
      environment as compared with that in a normal calcium environment, because the
      activation of NF-kappaB is required for the dissociation of the cytoplasmic
      heterodimer after the phosphorylation of IkappaB. From these facts, it was
      suggested that gene transcription factor NF-kappaB is intimately associated with
      inhibitory bone formation in osteoblastic cells.

PMID- 9585148
TI  - Regulatory mechanisms of calcium sensitization of contractile elements in smooth
      muscle.
AB  - It is evident that smooth muscle contraction is regulated not only by the
      Ca2+/calmodulin/myosin light chain kinase system but also by modulation of Ca2+
      sensitivity. Changes in free calmodulin concentrations, myosin light chain
      phosphorylation elicited by rho/rho-kinase, regulation of myosin phosphatase
      activity and thin filament-linked mechanisms are the possible mechanisms for
      regulation of Ca2+ sensitivity.

PMID- 9585149
TI  - Digital imaging of intracellular Ca2+ signaling in rat parotid acinar cells.
AB  - Utilizing digital imaging microscopy, the receptor-mediated changes in cytosolic
      Ca2+ concentration ([Ca2+]i) were studied in fura-2-loaded rat parotid acinar
      cells. The increase in [Ca2+]i induced by carbachol was initiated in the apical
      pole of the acinar cells and then spread as a Ca2+ wave toward the basolateral
      region. A similar polarization of Ca2+ signal was observed when the acinar cells
      were stimulated with substance P or phenylephrine. As the microsomal Ca2+-ATPase
      inhibitor thapsigargin did not produce a Ca2+ wave, activation of
      phosphoinositide hydrolysis is probably essential to trigger the Ca2+ wave.
      Stimulation with 1 microM isoproterenol, a concentration which causes the maximum
      release of amylase, had no effect on [Ca2+]i. Extracellular ATP (0.5 mM) induced
      a homogeneous increase in [Ca2+]i throughout the cells in the presence of
      extracellular Ca2+ but did not change [Ca2+]i in the absence of extracellular
      Ca2+, indicating that the ATP-induced rise in [Ca2+]i, is due to Ca2+ entry.

PMID- 9585150
TI  - Properties of calcium channels coupled to endogenous glutamate release from the
      vascularly perfused rat stomach in vitro.
AB  - We have demonstrated that both high-K+ and electrical stimulation of the vagus
      nerves release endogenous glutamate from the vascularly-perfused rat stomach in a
      calcium-dependent manner. In the present study, we examined properties of calcium
      channel subtypes mediating endogenous glutamate release from the stomach.
      Application of 50 mM KCl elicited a release of glutamate, and this release was
      abolished in calcium-free medium. The release of glutamate was significantly
      inhibited by both omega-agatoxin IVA, a P/Q-type calcium channel antagonist, and
      isradipine, an L type calcium channel antagonist. Omega-conotoxin GVIA, an N type
      calcium channel antagonist and flunarizine, a nonselective T-type calcium channel
      antagonist were without effect. In contrast to this case of glutamate, omega
      conotoxin GVIA induced a marked inhibition in the release of gastric
      noradrenaline. The combined treatment with omega-agatoxin IVA plus isradipine
      produced a marked synergistic inhibition of the glutamate release. This
      inhibition was, however, much less than that by cadmium. The present results
      suggest that P/Q and L type calcium channels coexist to regulate the release of
      gastric glutamate. Furthermore, it is possible that unidentified calcium channels
      other than P/Q and L type channels are also involved in the release of glutamate
      in the stomach.

PMID- 9585151
TI  - Ca2+-sensitive adenylyl cyclases, key integrators of cellular signalling.
AB  - The concept of second messenger signalling originated from the discovery of the
      role of cyclic AMP, although it is now known that cytosolic calcium [Ca2+]i
      mediates numerous signalling pathways and plays an equally vital role in many
      cellular events. In the last few years there has been a great deal of interest in
      the substantial molecular and functional diversity of mammalian adenylyl cyclases
      (ACs). Although AC was viewed as a generic activity, which was either stimulated
      or inhibited by stimulatory or inhibitory receptors, respectively, acting via
      alpha-subunits of trimeric GTP-regulatory proteins, the recent cloning of nine
      full-length isoforms, which significantly differ in their regulatory properties
      and tissue distributions, has revealed an unexpected level of complex regulation.
      In fact, each AC may integrate convergent inputs from many distinct signal
      generating pathways. The nine isoforms can be divided into four distinct
      families, which reflect their distinct patterns of regulation by betagamma
      subunits of G-proteins, protein kinase C (PKC) and Ca2+. The mechanisms of
      regulation are often highly synergistic or conditional, suggesting a function of
      ACs as coincident detectors. Since all nine isoforms can be regulated either
      directly or indirectly by Ca2+ or PKC, a complex range of responses is possible.
      The Ca2+ concentration that stimulates the major ACs in brain has been found to
      inhibit AC activity in a number of peripheral tissues and cell lines. The purpose
      of this article is to review many of the important aspects about the distinct
      regulatory properties and cellular distribution of Ca2+-regulated ACs. Indeed,
      the notion that Ca2+ and cAMP are "synarchic" messengers acting in concert to
      regulate cellular activity was formally proposed some time ago. Here, we will
      focus on acute interactions between Ca2+ and cAMP and attempt to understand how
      AC activities can be regulated by discrete, physiological [Ca2+]i rises in intact
      cells. All Ca2+-regulated isoforms have characteristic distribution patterns in
      the brain. Also discussed are emerging insights on the temporal and spatial
      regulation of Ca2+- and cAMP-regulated pathways which may enable cell stimuli to
      elicit specific responses.

PMID- 9585152
TI  - Calcium signaling and protein kinase C for TNF-alpha secretion in a rat mast cell
      line.
AB  - In mast cells, like other nonexcitable cells, receptor activation produces Ca2+
      mobilizing second messengers such as inositol 1,4,5-triphosphate or sphingosine-1
      phosphate, which induce Ca2+ release from internal stores. The resulting
      depletion of Ca2+ stores activates Ca2+ channels in plasma membranes designated
      as Ca2+ release-activated Ca2+ (CRAC) channels. Ionomycin appears to cause
      activation of CRAC channels by depleting intracellular Ca2+ stores rather than by
      acting as an ionophore. We compared the effects of azelastine, an anti-allergic
      drug, on TNF-alpha secretion, on Ca2+ signal, and on degranulation in an antigen-
      or ionomycin-stimulated rat mast RBL-2H3 cell line. Azelastine inhibited TNF
      alpha release at concentrations lower than those needed for the inhibition of
      degranulation. In antigen-stimulated cells, azelastine also inhibited
      equipotently TNF-alpha mRNA expression/protein synthesis, TNF-alpha release and
      Ca2+ influx. In ionomycin-stimulated cells, however, azelastine inhibited TNF
      alpha release to a greater extent than TNF-alpha mRNA expression/protein
      synthesis and Ca2+ influx, indicating that azelastine inhibits the release
      process more potently than transcription or production of TNF-alpha by
      interfering with a signal other than Ca2+. Pretreatment with 1 microM azelastine
      inhibited ionomycin-induced, but not antigen-induced, protein kinase C
      translocation to the membranes. These results suggest that TNF-alpha
      transcription/production is mainly regulated by Ca2+ influx, but the release
      process of TNF-alpha is regulated by additional mechanism(s) possibly involving
      activation of protein kinase C.

PMID- 9585153
TI  - The use of irreversible ligands to inactivate receptor subtypes: 4-DAMP mustard
      and muscarinic receptors in smooth muscle.
AB  - Irreversible ligands are useful tools for investigating the function of receptor
      subtypes in various physiological processes. The mechanism for alkylation
      involves the formation of a reversible receptor complex followed by a covalent
      reaction. The extent of receptor alkylation is determined by the dissociation
      constant of the reversible complex and the rate constant for conversion to the
      covalent complex. Selectivity can be achieved if the irreversible ligand exhibits
      a difference in its dissociation constants for receptor subtypes. Selective
      alkylation can also be achieved using a selective competitive inhibitor to
      protect the desired receptor subtype. By using the non-M2-selective irreversible
      antagonist, 4-DAMP mustard, in combination with the competitive M2-selective
      antagonist, AF-DX 116, it has been possible to achieve a highly selective
      inactivation of all non-M2 subtypes of the muscarinic receptors in smooth muscle
      and has enabled the discovery of the functional role of M2 receptors in smooth
      muscle.

PMID- 9585154
TI  - Intracellular calcium signaling systems in the pathophysiology of affective
      disorders.
AB  - In this paper, we show the importance of intracellular calcium (Ca2+) signaling
      systems in the pathophysiology of mood disorders based on our recent work.
      Patients with affective disorders appear to have an enhanced intracellular Ca2+
      rise in response to serotonin. We have observed effects of antidepressant drugs
      on intracellular Ca2+ signaling in rat cultured neuronal cells and glioma cells,
      and found that acute application of several classes of antidepressant drugs
      inhibited intracellular Ca2+ signaling and Ca2+-related signaling. It is
      important to investigate the role of intracellular Ca2+ signaling system for an
      understanding of the pathophysiology of affective disorders.

PMID- 9585155
TI  - Role of nerve terminal L-type Ca2+ channel in the brain.
AB  - The microinjection of Bay K 8644 (BAYK), an L-type Ca2+ channel stimulant, into
      rat caudate putamen dose-dependently potentiated locomotor activity. DA receptor
      antagonists significantly blocked BAYK-induced hyperactivity. Striatal DA levels
      as detected by microdialysis increased 140 fold above steady state levels 20 min
      after BAYK administration into caudate putamen. This increase was not influenced
      by a Na+ channel blocker. Pretreatment with 1,4-dihydropyridine (DHP) L-type Ca2+
      channel antagonists, but not nifedipine, into caudate putamen significantly
      blocked the BAYK induced-hyperactivity and DA efflux. The lowest level of
      intracellular DA detected by fluorohistochemistry coincided with the highest
      level of extracellular DA. These results indicate that the extraordinary DA
      release is regulated by a subtype of L-type Ca2+ channel that is present in the
      nerve terminal.

PMID- 9585156
TI  - Lack of tolerance in peripheral opioid analgesia in mice.
AB  - We recently developed a sensitive peripheral analgesic test in mice. Bradykinin,
      a representative pain-producing substance, when given subcutaneously through a
      polyethylene tube into the plantar of the limb connected to a transducer, induced
      a flexor reflex response, in a dose dependent manner. When morphine, a mu-opioid
      receptor agonist, was added to the plantar through another polyethylene tube,
      bradykinin-induced responses were completely abolished in a naloxone-reversible
      manner. These peripheral analgesic effects were also observed with DAMGO, another
      mu-opioid receptor agonist, and U-69,593, a kappa-opioid receptor agonist, but
      not DSLET, a delta-opioid receptor agonist. When morphine was given
      subcutaneously to the back, a potent analgesia in the tail pinch test was
      observed. Repeated administrations of morphine once per day for 5 days showed a
      marked tolerance or reduction in morphine analgesia on the 6th day, while there
      was no significant reduction in the peripheral analgesia of morphine. These
      findings suggest that tolerance to morphine analgesia is mediated through
      synaptic plasticity in the central nervous system, but not through a receptor
      desensitization at the level of the single cell.

PMID- 9585157
TI  - Alteration in Ca2+/calmodulin-sensitive adenylyl cyclase activity in the
      hippocampus of stroke-prone spontaneously hypertensive rats.
AB  - This study examined the function of adenylyl cyclase (AC) activity in the
      hippocampus and cerebral cortex of the stroke-prone spontaneously hypertensive
      rat (SHRSP). Male SHRSP (8-week-old and 25-week-old) were used for the
      experiments, and age-matched Wistar-Kyoto rats (WKY) were used as a genetic
      control. Basal, forskolin-, and GppNHp-stimulated AC activities were not
      different between SHRSP and WKY in the 8-week-old and 25-week-old groups.
      Ca2+/calmodulin-sensitive AC activity in hippocampal and cerebral cortex
      membranes was significantly lower in 25-week-old SHRSP than in age-matched WKY,
      but it was not in the 8-week-old group. These results suggest that the function
      of Ca2+/calmodulin-sensitive, presumably type I, AC was impaired in the brain of
      SHRSP. Such dysfunction of AC possibly contributes to the behavioral impairment
      reported in passive avoidance tasks in SHRSP.

PMID- 9585158
TI  - Effect of docosahexaenoic acid on smooth muscle cell functions.
AB  - There is increasing evidence that fish oil-enriched diets attenuate the
      progression of several types of human and experimental renal, intestinal and
      cardiovascular disorders, including hypertension. Docosahexaenoic acid (DHA), may
      be one of the active biological component. We previously reported that dietary
      DHA suppressed the progression of hypertension in stroke-prone spontaneously
      hypertensive rats (SHRSP). The purpose of this study is to clarify the in vitro
      effect of DHA on cultured smooth muscle cell functions such as cell growth,
      hypertrophy, NO release, and intracellular Ca2+ metabolism, which are involved in
      the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium
      of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto
      rats (WKY) had no significant effects on cell growth or on cell hypertrophy
      induced by angiotensin II as measured by flow cytometry. DHA had no stimulatory
      effect on interleukin-1beta (10 ng/ml)-induced nitric oxide release from smooth
      muscle cells of SHRSP, but rather slightly inhibited it. However, the treatment
      of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed
      the increase in intracellular Ca2+ concentration induced by angiotensin II, but
      not by thapsigargin. This was due to the suppression of Ca2+ influx, as
      determined by Mn2+ influx experiment. These results indicate that DHA
      specifically suppresses Ca2+ mobilization into smooth muscle cells. This may be
      one of the mechanisms by which dietary DHA prevents the development of
      hypertension in SHRSP.

PMID- 9585159
TI  - A new approach to the development of anti-ischemic drugs: protective drugs
      against cell injury induced by lysophosphatidylcholine.
AB  - Recent studies have revealed that lysophosphatidylcholine (LPC) produces
      mechanical and metabolic derangements in perfused working rat hearts and Ca2+
      overload in isolated cardiac myocytes. Thus, LPC possesses an ischemia-like
      effect on the heart. Therefore, a drug that possesses an anti-LPC action would
      protect or improve ischemia/reperfusion damage. We examined the effects of
      various anti-ischemic drugs on the Ca2+ overload induced by LPC. Our data suggest
      that a drug with high lipophilicity possesses a protective effect on cell injury
      induced by LPC, probably because of preservation of membrane integrity.

PMID- 9585160
TI  - Acetylcholine synthesis and muscarinic receptor subtype mRNA expression in T
      lymphocytes.
AB  - We used a sensitive and specific radioimmunoassay for acetylcholine (ACh), and
      detected significant amounts of ACh in the blood of various mammals, including
      humans. About 60% of human blood ACh was localized in mononuclear leukocytes.
      Human leukemic T-cell lines, used as T-lymphocyte models, contained both ACh and
      choline acetyltransferase (ChAT) activity. Furthermore, ChAT mRNA and protein
      were detected in the T-cell line MOLT-3. Phytohemagglutinin, a T-cell activator,
      increased both synthesis and release of ACh by MOLT-3 cells. Muscarinic receptor
      subtype mRNA expression was confirmed in various T-cell lines. These findings
      indicate that ACh synthesized by ChAT in T-lymphocytes acts on the muscarinic
      receptors on lymphocytes in autocrine and/or paracrine pathways and suggest that
      ACh in blood functions as a modulator of T-cell-dependent immune responses.

PMID- 9585161
TI  - Molecular biology of microglia cytokine and chemokine receptors and microglial
      activation.
AB  - Activation of brain microglial cells can be subdivided into a number of stages.
      Early stages likely are proliferation and migration to sites of cell damage.
      These two stages have been studied exemplarily on the IL-3 receptor beta-subunit
      and on the CC-chemokine receptor 5 using molecular biological methods. First, IL
      3 receptor beta-subunit cDNA has been cloned in full length from rat microglia.
      Since cultured microglia are already activated to some extent, mRNA of this
      subunit has been detected in the isolated cells, but was absent in normal rat
      brain. Lipopolysaccharide (LPS) increased this mRNA in the cultured cells and LPS
      injected into the circulation of rats induced the mRNA specifically in brain
      microglia as revealed by in situ hybridizations. Next, we obtained partial cDNAs
      of receptor-coupled protein tyrosine kinases JAK 1 and JAK 2. These mRNAs were
      present both in cultured microglia and in rat brain, but were not influenced by
      LPS. Finally, a full-length cDNA of the rat chemokine receptor 5 has been
      obtained by PCR methodology. Its mRNA was increased by administration of LPS both
      in cultured microglia and in vivo. It is expected, that further investigations on
      these receptors could help to develop improved strategies to combat chronic
      inflammatory events in the brain.

PMID- 9585162
TI  - Role of endothelin B receptor signals in reactive astrocytes.
AB  - We investigated the involvement of endothelinB receptor signals in the activation
      of astrocytes in vitro and in vivo. Endothelin reversed the stellate morphology
      of astrocytes induced by several agents. Endothelin stimulates astrocytic stress
      fiber formation. This effect of endothelin is Ca2+-independent and mediated by
      rho protein signal cascades linked to tyrosine phosphorylation. Injection of
      endothelin into striatum caused reactive astrocytosis which is prevented by a
      systemic injection of endothelinB receptor antagonist. We propose the role of
      endothelinB receptor signal transduction in reactive astrocytes.

PMID- 9585163
TI  - Induction of inducible nitric oxide synthase and heme oxygenase-1 in rat glial
      cells.
AB  - Recent observations suggest a possible interaction between the nitric oxide
      (NO)/NO synthases and carbon monoxide (CO)/heme oxygenases systems. We examined
      the effects of lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and NO
      donor such as S-nitroso-N-acetylpenicillamine (SNAP) on induction of inducible NO
      synthase (iNOS) and heme oxygenase-1 (HO-1) in mixed glial cells and in rat
      hippocampus. In in vitro glial cells, treatment with LPS induced the expression
      of 130-kDa iNOS after 6 h, and NO2- accumulation and enhancement of the protein
      level of 33-kDa HO-1 after 12 h. In addition, treatment with SNAP induced HO-1
      expression after 6 h. Although a NOS inhibitor, such as N(G)-nitro-L-arginine
      (NNA), did not change LPS-induced iNOS expression, the inhibitor suppressed both
      NO2- accumulation and the enhancement of HO-1. Immunocytochemistry showed that
      LPS-treatment induced iNOS-immunoreactivity predominantly in microglia, while
      this treatment induced HO-1-immunoreactivity in both microglia and astrocytes.
      These results suggest that endogenous NO production by iNOS in microglia causes
      autocrine- and paracrine-induction of HO-1 protein in microglia and astrocytes in
      rat brain.

PMID- 9585164
TI  - Identification of opioid receptor subtypes in antinociceptive actions of
      supraspinally-administered mitragynine in mice.
AB  - Mitragynine (MG), a major alkaloidal constituent extracted from the plant
      Mitragyna speciosa Korth, is known to exert an opioid-like activity. Our previous
      study showed the involvement of opioid systems in the antinociceptive activity of
      MG in the tail-pinch and hot-plate tests in mice. In the present study, to
      clarify the opioid receptor subtypes involved in the antinociceptive action of
      MG, we investigated the effects of selective antagonists for mu-, delta- and
      kappa- opioid receptors on antinociception caused by the intracerebroventricular
      (i.c.v.) injection of MG in the tail-pinch and hot-plate tests in mice. The
      coadministration of a selective mu-opioid antagonist, cyprodime (1-10 microg,
      i.c.v.) and the pretreatment with a selective mu1-opioid antagonist naloxonazine
      (1-3 microg, i.c.v.) significantly antagonized the antinociceptive activities of
      MG (10 microg, i.c.v.) and morphine (MOR, 3 microg, i.c.v.) in the tail-pinch and
      hot-plate tests. Naltrindole (1-5 ng, i.c.v.), a selective delta-opioid
      antagonist, also blocked the effects of MG (10 microg, i.c.v.) without affecting
      MOR (3 microg, i.c.v.) antinociception. Nor-binaltorphimine, a selective kappa
      opioid antagonist, significantly attenuated MG (10 microg, i.c.v.)
      antinociception in the tail-pinch test but not in the hot-plate test at the dose
      (1 microg, i.c.v.) that antagonized the antinociceptive effects of the selective
      kappa-opioid agonist U50,488H in both tests, while it had no effect on MOR
      antinociception in either tests. These results suggest that antinociception
      caused by i.c.v. MG is dominantly mediated by mu- and delta-opioid receptor
      subtypes, and that the selectivity of MG for the supraspinal opioid receptor
      subtypes differs from that of MOR in mice.

PMID- 9585165
TI  - Evidence for the role of follicle stimulating hormone in maintaining the oocyte
      meiotic arrest in pre-antral follicles.
AB  - The study was designed to clarify the physiological role of FSH in maintaining
      the meiotic arrest in vitro of oocytes derived from intact and from
      hypophysectomized hamsters. The sensitivity to FSH in maintaining the meiotic
      arrest of oocytes during incubation of pre-antral follicles of adult golden
      hamsters was estimated: log dose-response curves were characterized by an ED50 of
      about 0.2 pg FSH/ml (= 1 microU). After hypophysectomy oocytes of the pre-antral
      follicles were screened for the presence of a germinal vesicle (GV). The
      breakdown of the GV (GVBD) rose from 0 on day 0 to 48.8 +/- 13.8% on day 1, to
      55.9 +/- 6.8% on day 2 and to 64.3 +/- 7.4 on day 6 (p < 0.001 vs day 0).
      Incubation without FSH of the pre-antral follicles obtained from the same
      hypophysectomized animals showed an almost complete disappearance of the GV at
      the same time intervals. Incubation with 2 pg FSH/ml (= 10 microU) still
      demonstrated the inhibiting effect of FSH on the meiotic resumption: 13.4 +/-
      4.3% (day 0), 36.9 +/- 16.3% (day 1), 38.7 +/- 21.0% (day 2) and of 38.1 +/-
      12.6% (p > 0.1) on day 6. These results demonstrate that very low doses of FSH
      are able to maintain the meiotic arrest in oocytes of pre-antral follicles of the
      golden hamster and that deprivation of FSH by hypophysectomy involves a
      disappearance of GV oocytes to a certain extent.

PMID- 9585166
TI  - Involvement of high density lipoprotein as substrate cholesterol for
      steroidogenesis by bovine adrenal fasciculo-reticularis cells.
AB  - Adrenocorticosteroids are known to be synthesized from cholesterol which may
      arise from de novo synthesis or from the uptake of low-density lipoproteins (LDL)
      or high-density lipoproteins (HDL). LDL is reported to be a main substrate for
      corticosteroid synthesis by bovine adrenocortical cells, although the role of
      HDL, which is well known to be used for steroid biosynthesis in rat adrenals, is
      still obscure. Therefore, we examined the role of HDL in the regulation of
      corticosteroidogenesis in bovine adrenals in order to clarify whether or not HDL
      was selectively utilized for corticosteroid synthesis in vitro. The present data
      demonstrated that HDL and LDL increased cortisol production in a dose-dependent
      manner in bovine adrenocortical cells in vitro, and also that HDL cholesterol
      increased cortisol production significantly higher than LDL cholesterol did.
      Addition of adrenocorticotrophic hormone (ACTH) with HDL to the incubation media
      enhanced much higher cortisol production than that with LDL in short time
      incubation. The present data also demonstrated that uptake of 125I-HDL was
      significantly greater than that of 125I-LDL. Thus, HDL rather than LDL is thought
      to be the preferred lipoprotein as a source of steroidogenic substrate
      cholesterol in bovine adrenal fasciculo-reticularis cells.

PMID- 9585167
TI  - Measurement and prediction of sympathetic nervous system activity in humans.
AB  - The measurement of norepinephrine (NE) kinetics has broadened our understanding
      of sympathetic nervous system activity involvement in energy expenditure, blood
      pressure regulation and substrate utilization. This methodology, however, has
      several disadvantages that include administration of radioactivity to volunteers,
      its expense, and time consuming laboratory analyses. Thus, we developed an
      equation to predict plasma NE appearance rate (NEAP) derived from infusions of
      tritiated norepinephrine performed in 113 healthy men (18-78 yr.). The accuracy
      of the equation was tested using cross-validation procedures. Age, fat mass,
      plasma [NE], waist circumference, and body weight (BW) correlated significantly
      with plasma NE appearance rate. The resulting prediction equation in the
      validation group was: NEAP = 0.00003148 BW [NE], with R2 = 0.76 and was
      successfully cross-validated. Using pooled data from both groups the prediction
      equation was: NEAP (microg/min) = 0.00003108 x [NE (pg/ml)] x [Body weight (kg)]
      with an R2 = 0.70 and SEE = 0.096 microg/min. The magnitude of error associated
      with this equation allows for detection of age-associated, exercise-induced
      changes and blood pressure-related differences in plasma NE appearance rate
      published in the literature. We provide an equation that offers a relatively
      simple and accurate alternative to estimate plasma NE appearance from the
      measurement of arterialized plasma [NE] and body weight.

PMID- 9585168
TI  - Cloning of bovine preproadrenomedullin and inhibition of its basal expression in
      vascular endothelial cells by staurosporine.
AB  - The cDNA encoding preproadrenomedullin (preproAM) was cloned using reverse
      transcriptase polymerase chain reaction (RT-PCR) and 5' rapid amplification of
      cDNA ends from total RNA from bovine aortic endothelial cells (BAEC). Bovine
      preproAM cDNA shows high sequence homology with human, porcine and rat preproAM.
      Bovine-specific primers derived from this sequence were used in RT-PCR to study
      regulation of this gene. Treatment of BAEC or a human endothelial cell line
      (Ea.hy 926) with the non-selective protein kinase inhibitor staurosporine
      resulted in significantly reduced preproAM mRNA levels. The reduction in preproAM
      mRNA appeared to be absolute when Ea.hy 926 cells were exposed to 100 nM
      staurosporine for 2 h. However, this dramatic reduction could not be reproduced
      by treatment with the protein kinase A (PKA) inhibitor H-89, or the protein
      kinase C (PKC) inhibitors chelerythrine chloride and bisindolylmaleimide I. These
      observations suggest that activation of a novel staurosporine-sensitive protein
      kinase is necessary for basal expression of the preproAM gene in these cells.

PMID- 9585169
TI  - Hypothalamic-pituitary-adrenal axis activity in the inbred Brown Norway and
      Fischer 344 rat strains.
AB  - We have examined the basal and the stress-induced secretion of corticosterone in
      relation to the expression of adrenal steroid receptors in the pituitary,
      hypothalamus and hippocampus of the inbred Brown Norway and Fischer 344 rat
      strains. Our data indicated that plasma transcortin and integrated plasma
      corticosterone levels were significantly higher in Fischer 344 compared to Brown
      Norway rats. Fischer 344 hypersecrete corticosterone during the dark phase of the
      diurnal cycle and during the phase of recovery following a 20 min period of
      restraint stress compared to Brown Norway rats. This hypersecretion of
      corticosterone was negatively correlated with the size of the adrenal gland but
      might be related to the higher density of mineralocorticoid receptors in the
      hippocampus of Fischer 344 rats.

PMID- 9585170
TI  - Hyperpolarization of the rat hepatocyte membrane by 2,5-anhydro-D-mannitol in
      vivo.
AB  - The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM), that inhibits glucose
      release and ATP formation in liver cells, seems to stimulate feeding by acting on
      the liver, because hepatic portal injection was more effective than jugular vein
      injection and because hepatic branch vagotomy attenuated 2,5-AM's hyperphagic
      effect. Russek's "potentiostatic" hypothesis postulates a role for the hepatic
      membrane potential in the control of food intake with depolarization of
      hepatocytes signaling hunger and hyperpolarization representing a satiety signal.
      Therefore, the aim of the present study was to find out, whether 2,5-AM affects
      the hepatic membrane potential under in vivo conditions. The membrane potential
      was measured with microelectrodes in anesthetized rats after intraperitoneal
      (i.p.) or intraportal (i.p.v.) administration of 2,5-AM or control solution. 2,5
      AM significantly hyperpolarized the hepatocyte membrane 50 min after i.p.
      injection (100 mg/kg: 3.6 mV; 300 mg/kg: 9.9 mV). In a second experiment, 2,5-AM
      (300 mg/kg) elicited a significant hyperpolarization of hepatocytes as soon as 5
      9 min after i.p.v. infusion. These effects occurred at doses that have been shown
      to increase the afferent discharge rate in the common hepatic vagus branch, and
      to stimulate food intake. 2,5-AM's hyperphagic effect therefore is associated
      with an increase in the hepatic membrane potential. These findings contradict the
      predictions of the "potentiostatic" hypothesis and are consistent with the
      notion, that the feeding response to 2,5-AM might be due to ATP depletion in the
      terminals of vagal afferents.

PMID- 9585171
TI  - Safety and tolerability of metrifonate in patients with Alzheimer's disease:
      results of a maximum tolerated dose study.
AB  - Metrifonate, a pro-drug that is transformed non-enzymatically into a potent
      inhibitor of acetylcholinesterase (AChE), has been used in the tropics for over
      30 years for the treatment of schistosomiasis. A pilot study, and Phase I and
      Phase II studies of metrifonate in Alzheimer's disease (AD) patients conducted
      prior to the current study showed benign, dose-dependent adverse event profiles
      consisting primarily of gastrointestinal events, optimal daily dosing with a
      loading phase (in the absence of a loading dose phase, 6-8 weeks were required to
      attain steady-state AChE inhibition levels), and an improvement in Alzheimer's
      Disease Assessment Scale (ADAS) scores. The current open-label study was designed
      to evaluate the safety and tolerability of relatively high loading doses,
      followed by lower maintenance doses of metrifonate in the same patient
      population, and to determine the maximum tolerated dose (MTD) of metrifonate.
      Accordingly, the first cohort of 8 probable AD patients (per National Institute
      of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and
      Related Disorders Association [NINCDS-ADRDA] criteria) were administered once
      daily loading doses of 2.5 mg/kg (125-225 mg) for 14 days, followed by 4.0 mg/kg
      (200-360 mg) for an additional 3 days. These patients were maintained on once
      daily doses of 2.0 mg/kg (100-180 mg) for 14 days. AChE inhibition for this
      cohort ranged from 88% to 94%. On Day 28 of 31, this cohort was discontinued due
      to moderate to severe side effects in 6 patients; consequently, the second cohort
      of 8 probable AD patients received a once-daily loading dose of 2.5 mg/kg (125
      225 mg) for 14 days followed by a once-daily maintenance dose of 1.5 mg/kg (75
      135 mg) for 35 days. This maintenance dose yielded an AChE inhibition level
      ranging from 89% to 91%. In spite of an AChE inhibition level comparable to that
      achieved with the higher dose, the reduced dose was associated with a more
      favorable adverse event profile which was mainly gastrointestinal and
      musculoskeletal in nature. The maximum tolerated dose was established at 1.5
      mg/kg/day (75-135 mg/day) for maintenance dosing in AD patients.

PMID- 9585172
TI  - The delta2-opioid receptor subtype stimulates phosphoinositide metabolism in
      mouse periaqueductal gray matter.
AB  - The delta(delta)-opioid agonists [D-Pen2,5]enkephalin (DPDPE) and [D
      Ala2]deltorphin II increased the formation of inositol phosphates (IPs) in mice
      periaqueductal gray matter (PAG) slices pre-labeled with myo-[3H]inositol. Both
      delta-agonists caused an increase in IP accumulation in a dose-dependent manner
      (1-100 microM) and which was pertussis toxin (0.5 microg/mouse, i.c.v.)
      sensitive. This effect was blocked by the delta-antagonist ICI-174.864 (10
      microM). The presence of subtypes of the delta-opioid receptor (delta1 and
      delta2) in PAG has been suggested by pharmacological studies. In this brain
      structure, naltrindrole 5'-isothiocyanate (5'-NTII), but not 7
      benzylidenenaltrexone (BNTX), antagonized the effects of DPDPE and [D
      Ala2]deltorphin II, suggesting the involvement of a population of delta receptors
      sensitive to the delta2-antagonist NT II on this effect. To further investigate
      the participation of delta-receptor subtypes in the stimulation of IPs formation,
      mice were injected with antisense oligodeoxynucleotides (ODNs) directed to
      nucleotides 7-26 or 2946 of the cloned delta-receptor mRNA, and PAG slices from
      these animals were used in in vitro assays. The results demonstrate that the
      reported increase of phosphoinositide (PI) hydrolysis depends on the agonist
      activation of the delta2-opioid receptor subtype in the PAG.

PMID- 9585173
TI  - Lafutidine-induced stimulation of mucin biosynthesis mediated by nitric oxide is
      limited to the surface mucous cells of rat gastric oxyntic mucosa.
AB  - Although the new histamine H2 receptor antagonist, lafutidine (FRG-8813), N-[4-[4
      (piperidinylmethyl)pyridyl-2-oxy]-(Z)-2-butenyl]-2-(fur furylsulfinyl)acetamide
      accelerates mucin metabolism of rat gastric mucosa, the physiological mechanisms
      by which this drug stimulates the biosynthesis remain unclear. In this paper, we
      report the effect of lafutidine on mucin biosynthesis in distinct sites and
      layers of rat gastric mucosa, including the possible participation of nitric
      oxide (NO). Lafutidine enhanced [3H]glucosamine incorporation into the mucin in
      the full thickness corpus mucosa, but not in the antrum. This stimulation on
      mucin biosynthesis disappeared by the removal treatment of surface mucosal cells.
      The lafutidine-induced increase of [3H]-labeled mucin in the corpus was
      completely blocked by either NG-nitro-L-arginine (10[-5] M) or 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazolne-1-oxyl-3-oxide (10[-5] M). The
      inhibitory action of NG-nitro-L-arginine was totally reversed by L-arginine (5 x
      10[-3] M). These results suggest that the lafutidine-induced stimulation of mucin
      biosynthesis mediated by NO is limited to the surface mucous cells of rat gastric
      oxyntic mucosa.

PMID- 9585174
TI  - Screen of receptor and uptake-site activity of hypericin component of St. John's
      wort reveals sigma receptor binding.
AB  - The mechanism of the antidepressant action of St. John's wort (Hypericum
      perforatum) remains unknown. A central component similar to that of the other
      clinically-popular antidepressants (e.g., inhibitors of 5-HT or norepinephrine
      reuptake or MAO) is suspected to play a role, but other mechanisms distinct from
      the SSRIs, NSRIs or MAOIs are possible. The extract of St. John's wort that is
      used clinically consists of multiple compounds. Hypericin is believed to be one
      of the major components responsible for the antidepressant effect. In the present
      study, the affinity of hypericin was determined at thirty receptor or reuptake
      sites. At 1.0 microM, hypericin inhibited less than 40% of specific radioligand
      binding at all sites except mAChR and sigma receptors. The demonstration of sigma
      receptor binding of hypericin is a novel finding and it might contribute to a new
      understanding of the clinical attributes of St. John's Wort.

PMID- 9585175
TI  - Inhibitory effects of tyrosine kinase inhibitors on capacitative Ca2+ entry in
      rat glioma C6 cells.
AB  - The effects of genistein and erbstatin analogue, inhibitors of tyrosine kinase,
      on Ca2+ mobilization evoked by thapsigargin (TG) were examined in rat glioma C6
      cells. Genistein and erbstatin analogue inhibited the Ca2+ release from
      intracellular pools as well as Ca2+ entry from extracellular medium evoked by TG
      in a dose-dependent manner. However, they did not affect a Ca2+ entry due to
      leakage of Ca2+ from extracellular medium into cells. The present results suggest
      that tyrosine kinase inhibitors inhibit capacitative Ca2+ entry due to the
      inhibition of both Ca2+ entry itself and Ca2+ release in rat glioma C6 cells.

PMID- 9585176
TI  - Molecular biology of stress responses in India.

PMID- 9585177
TI  - Definition of extracellular localized epitopes of Hsp70 involved in an NK immune
      response.
AB  - In order to define extracellular localized epitopes of Hsp70 on human tumor cells
      which are accessible to the immune system, six commercially available Hsp70
      specific monoclonal antibodies (mAb) with different recognition sites were
      examined by immunological approaches. The recognition pattern of these antibodies
      was analyzed on purified recombinant Hsp70 proteins (rHsp70, Hsc70, DnaK), on
      lysates of Hsp70-expressing colon carcinoma cells (CX+) and on lysates of M21 rat
      1 cells that overexpress human Hsp70 or Hsp70 fragments: ABgl (del 120-428)
      consisting of the C-terminal part and ASma (del 438-618) consisting of the N
      terminal part of human Hsp70. All antibodies reacted equally well with rHsp70 and
      cytoplasmic Hsp70 derived from human tumor cells or M21 rat-1 cells. Only one
      antibody (MA3-007; Hsp70, Hsc70) detects a region localized within the ATPase
      domain of Hsp70 (amino acid 122-264) and reacts positively with the C-terminal
      deletion mutant ASma. All other antibodies, including RPN1197 are directed
      against the C-terminal peptide binding domain of Hsp70 and react positively with
      the N-terminal deletion mutant ABgl. Although all six antibodies detect full
      length Hsp70 protein, derived from plasma membrane fractions of CX+ tumor cells,
      cell surface expressed Hsp70 on viable CX+ tumor cells, as determined by
      flowcytometry, is only recognized with the antibodies MA3-006 (Hsp70, Hsc70; 504
      617), MA3-009 (Hsp70; 504-617) and RPN1197 (Hsp70). An estimation of the ratio of
      membrane-bound to cytoplasmic Hsp70 molecules revealed that 15-20% of total Hsp70
      molecules are expressed on the plasma membrane. This tumor-selective cell surface
      expression of Hsp70 correlates with an increased sensitivity to lysis mediated by
      non-MHC restricted natural killer (NK) cells. We demonstrate that only antibodies
      directed against membrane-bound Hsp70 (MA3-006, MA3-009, RPN1197) inhibit NK
      killing activity against Hsp70-expressing tumor cells. Taken together our data
      indicate that at least the C-terminal region 504-617, that contains at least one
      single alpha-helix (amino acid 512-536), has to be localized extracellularly and
      might be of importance for an NK-mediated anti-tumor immune response.

PMID- 9585178
TI  - Mitochondrial localization and temporal expression of the Drosophila melanogaster
      DnaJ homologous tumor suppressor Tid50.
AB  - The Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal
      discs (tid) was identified as a homolog of all dnaJ-like genes known to date
      which have been well preserved in evolution. Homozygous D. melanogaster l(2)tid
      mutants l(2)tid1, l(2)tid2 and l(2)tid3 are characterized by neoplastic
      transformation of the adult integumental primordia, the imaginal discs, and the
      death at the time of puparium formation. The first part of this study is
      concerned with the identification and subcellular localization of the l(2)tid
      encoded protein, Tid50. The second part examines its tissue specific expression
      during wild-type development and in tumorous imaginal discs. To specify the
      function(s) of the Tid50 protein polyclonal rabbit antibodies directed against
      various domains of it were generated and used for staining of Western blots and
      whole-mounts and paraffin sections of various tissues isolated from wild-type and
      mutant tumor-developing animals. To identify the mutational events leading in
      homozygous l(2)tid mutants to abnormal expression level of l(2)tid-encoded RNA
      and protein, the mutant gene was isolated from homozygous l(2)tid1 and l(2)tid2
      animals and sequenced.

PMID- 9585179
TI  - Structure, function and evolution of DnaJ: conservation and adaptation of
      chaperone function.

PMID- 9585180
TI  - Identification of an integral membrane 80 kDa protein of Saccharomyces cerevisiae
      induced in response to dehydration.
AB  - Using SDS-PAGE gels we observed the induced synthesis of a protein with a
      molecular mass of 80 kDa when cells of strains of Saccharomyces cerevisiae were
      subjected to dehydration. Physiological analysis showed that this protein is not
      present during growth on glucose but was found in derepressed cells from
      stationary phase. Furthermore, its synthesis was induced when cells were grown on
      medium containing alpha-methyl-glucoside as carbon source. However, the 80 kDa
      protein was not found in cells of mutants unable to transport trehalose. This
      protein was localized in the cytoplasmic membrane and showed trehalose-binding
      activity, determined by its partial purification on a trehalose-Sepharose 6B
      affinity column. The possible involvement of the 80 kDa protein with the
      trehalose transport system is discussed.

PMID- 9585181
TI  - Hsp90-containing multiprotein complexes in the eukaryotic microbe Achlya.
AB  - In the oomycete fungus Achlya ambisexualis, hyphae of the male strain undergo
      sexual differentiation in the presence of the steroid hormone antheridiol.
      Earlier studies demonstrated that antheridiol binds with high affinity to a 9S
      multiprotein complex from A. ambisexualis cytosols. Although these complexes were
      found to contain the heat shock protein Hsp90, the other components were not
      known. It was of interest to determine if any of the other protein components in
      the Achlya Hsp90-heterocomplexes would be homologous to those found in the
      steroid receptor-Hsp90-heterocomplexes of vertebrates. Cytosolic proteins of 110
      kDa, 74 kDa, 64 kDa, 61 kDa, 56 kDa, 47 kDa, 27 kDa and 23 kDa, were found in
      repeated trials, to co-immunoprecipitate with Achlya Hsp90. The 74 kDa protein
      was identified as the heat shock protein Hsp70, the 23 kDa protein was found to
      be related to the vertebrate protein p23 and the 56 kDa protein was found to be
      related to immunophilin FKBP51. All three of these proteins are components of the
      vertebrate receptor heterocomplexes. The 110 kDa, 61 kDa and 27 kDa proteins
      appeared to be unique to the Achlya complexes. Unlike the seven other proteins co
      immunoprecipitating with Hsp90, the 61 kDa protein was observed only in the co
      immunoprecipitates produced from in vitro translates of RNA isolated from
      antheridiol-treated mycelia.

PMID- 9585182
TI  - Heat-induced proteolysis of HSF causes premature deactivation of the heat shock
      response in Nb2 lymphoma cells.
AB  - Nb2-11 cells, a prolactin (PRL)-dependent T-lymphoma cell line, display an
      unusual response to heat stress characterized by the lack of expression of
      inducible hsp70 mRNA transcripts and a reduction in the levels of constitutively
      expressed heat shock protein (HSP) genes. This aberrant heat shock response
      appears to result from heat-induced proteolytic fragmentation of heat shock
      factor (HSF). In this report, we have investigated processes that promote HSF
      fragmentation and identified characteristics of a protease that may be
      responsible for this effect. Cycloheximide did not affect HSF fragmentation of
      heat-shocked Nb2-11 cells suggesting that proteases responsible for this
      proteolysis are constitutively expressed and become activated by the heat shock
      conditions. PRL protected Nb2-11 cells from heat-induced fragmentation whereas
      sodium butyrate (NaBT) rendered a fragmentation-resistant cell line (Nb2-SFJCD1
      cells) sensitive to HSF proteolysis. Heat-induced HSF fragmentation in Nb2-11
      cells was not affected by pretreating cultures with several serine protease
      inhibitors. However, a dose-dependent decrease in HSF fragmentation was achieved
      by pretreating cultures with iodoacetamide, a cysteine protease inhibitor that is
      active in apoptosis. Apparently, the heat shock response in Nb2 cells is
      attenuated by a mechanism that involves the premature deactivation of HSF by its
      selective proteolysis. Attenuation of this critical cellular stress response may
      be an important contributor to the progression of hormone-dependent tumors
      possibly by influencing apoptotic processes known to regulate the activity of
      these cells.

PMID- 9585183
TI  - Effects of exogenous stress protein 70 on the functional properties of human
      promonocytes through binding to cell surface and internalization.
AB  - The presence of antibodies against the major stress protein, Hsp70, in patients
      with autoimmune diseases led us to hypothesize that Hsp70 may occur
      extracellularly, and could exert chaperoning and regulatory effects on various
      cells. We examined the action of pure Hsp/Hsc70 on the main physiological
      functions of human promonocytic U-937 cells. The protein was isolated from calf
      muscle and was shown to be a mixture of inducible Hsp70 (60%) and constitutive
      Hsc70 (40%) isoforms. It was observed that the addition of the protein up
      regulated two major monocyte/macrophage differentiation markers, CD11c and CD23,
      by 20-35%, while it had no effect on CD14. The experiments performed to
      investigate the influence of Hsp/Hsc70 on the reaction of U-937 cells to
      differentiation stimuli demonstrated that the addition of the protein prior to
      PMA was able to inhibit binding of proper transcription factors to double
      symmetry and cAMP-response elements of the c-fos early response gene promoter.
      Administration of exogenous Hsp/Hsc70 prior to treatment with the tumor necrosis
      factor-alpha significantly lowered the number of apoptotic and necrotic cells. In
      no case did the control protein, ovalbumin, taken in the same concentration give
      a comparable effect on U-937 cells. Since the Hsp/Hsc70 effects occurred within
      the first hour of co-incubation, and therefore they might be explained by its
      interaction with the cell surface, we assayed binding of the biotinylated protein
      to U-937 cells by immunoenzyme assay, flow cytometry and indirect
      immunofluorescence. Using these three techniques we were able to detect Hsp/Hsc70
      bound to cells after a 20 min incubation. According to flow cytometry data, at
      this time 32% of cells were positively stained with streptavidin-FITC.
      Immunofluorescence studies demonstrated Hsp/Hsc70 bound to the cell surface after
      a 20 min incubation followed by induction of patch and cap-like structures. One
      hour later, the majority of the protein had been internalized by U-937 cells.

PMID- 9585184
TI  - Why vaccines?

PMID- 9585185
TI  - Living up to the legacy.

PMID- 9585186
TI  - New vaccines are aimed at the rich says UNICEF. United Nations Children's Fund.

PMID- 9585187
TI  - Panel recommends White House coordinates AIDS vaccine development.

PMID- 9585188
TI  - Reactions to MMR immunization scare.

PMID- 9585189
TI  - Slow progress in malaria vaccine development.

PMID- 9585190
TI  - Vaccine visions and their global impact.

PMID- 9585191
TI  - For vaccines, the future is now.

PMID- 9585192
TI  - Win-win interactions between the public and private sectors.

PMID- 9585193
TI  - The role of US government agencies in vaccine research and development.

PMID- 9585194
TI  - Why do we not have an HIV vaccine and how can we make one? .

PMID- 9585195
TI  - Slaying the Hydra all at once or head by head?

PMID- 9585196
TI  - Alchemy for asthma.

PMID- 9585197
TI  - Pharmaceutical foodstuffs--oral immunization with transgenic plants.

PMID- 9585198
TI  - The global vaccine enterprise: a developing world perspective.

PMID- 9585199
TI  - Recruiting HLA to fight HIV.

PMID- 9585200
TI  - Vaccine production in Russia: an update.

PMID- 9585201
TI  - Six decades of vaccine development--a personal history.

PMID- 9585202
TI  - Vaccine developments.

PMID- 9585203
TI  - Research toward vaccines against malaria.

PMID- 9585204
TI  - Cancer vaccines.

PMID- 9585205
TI  - HIV vaccines--where are we going?

PMID- 9585206
TI  - Fields of pharmaceuticals.

PMID- 9585207
TI  - Genetic effects on HIV disease progression.

PMID- 9585208
TI  - HHV-6 and multiple sclerosis.

PMID- 9585209
TI  - HHV-6 and multiple sclerosis.

PMID- 9585210
TI  - UK government lobbying for increased spending on universities intensifies.

PMID- 9585211
TI  - Are Japanese researchers exploiting Thai HIV patients?

PMID- 9585212
TI  - Genetics research on the town hall agenda, courtesy of ELSI. Ethical, Legal, and
      Social Implications.

PMID- 9585213
TI  - Funding for Gallo Institute under threat.

PMID- 9585214
TI  - Wellcome Trust funds new "Medicine in Society" program.

PMID- 9585215
TI  - Dissent over plans to build Indian neuroscience center.

PMID- 9585216
TI  - Dengue fever on the increase.

PMID- 9585217
TI  - Cancer rates decline as cancer funding increases.

PMID- 9585218
TI  - Antibiotic resistance--what can we do?

PMID- 9585219
TI  - Site-directed immunogenesis.

PMID- 9585220
TI  - A vaccine for leprosy.

PMID- 9585221
TI  - Plants are not just passive creatures!

PMID- 9585222
TI  - Malaria: In the belly of the beast.

PMID- 9585223
TI  - The 'Fantastic Voyage' of muscle progenitor cells.

PMID- 9585224
TI  - Closer to neurogenesis in adult humans.

PMID- 9585225
TI  - Look on the bright side of cloning.

PMID- 9585226
TI  - Glimpsing the cause of rhabdomyosarcoma.

PMID- 9585227
TI  - Two deaf mice, two deaf mice...

PMID- 9585228
TI  - Reorganizing the brain.

PMID- 9585229
TI  - Chemokines and HIV-1 second receptors: the therapeutic connection.

PMID- 9585230
TI  - Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian
      rats.
AB  - Parkinson's disease symptoms can be improved by transplanting fetal dopamine
      cells into the putamen of parkinsonian patients. Because the supply of human
      donor tissue is limited and variable, an alternative and genetically modifiable
      non-human source of tissue would be valuable. We have generated cloned transgenic
      bovine embryos, 42% of which developed beyond 40 days. Dopamine cells collected
      from the ventral mesencephalon of the cloned fetuses 42 to 50 days post
      conception survived transplantation into immunosuppressed parkinsonian rats and
      cells from cloned and wild-type embryos improved motor performance. Somatic cell
      cloning can efficiently produce transgenic animal tissue for treating
      parkinsonism.

PMID- 9585231
TI  - The cyclin-dependent kinase inhibitor p27Kip1 safeguards against inflammatory
      injury.
AB  - The cyclin-dependent kinase inhibitor p27Kip1 controls cell proliferation in
      response to normal mitogenic stimuli. We show here that p27Kip1 also safeguards
      against excessive cell proliferation in specific pathophysiologic settings. We
      used experimental glomerulonephritis as a paradigm for immune mediated
      inflammation and ureteral obstruction as a model for non-immune mediated
      inflammation. Renal function was substantially decreased in nephritic p27-/- mice
      compared with control mice, and this was associated with increased glomerular
      cell proliferation, apoptosis and matrix protein accumulation. Tubular epithelial
      cell proliferation and apoptosis was also increased in p27-/- mice following
      ureteral obstruction. p27Kip1 may have a general role in protecting cells and
      tissues from inflammatory injury.

PMID- 9585232
TI  - Tumor immunogenicity is determined by the mechanism of cell death via induction
      of heat shock protein expression.
AB  - In situ killing of tumor cells using suicide gene transfer to generate death by a
      non-apoptotic pathway was associated with high immunogenicity and induction of
      heat shock protein (hsp) expression. In contrast, a syngeneic colorectal tumor
      line, CMT93, killed predominantly by apoptosis, showed low levels of hsp
      expression and less immunogenicity. When apoptosis was inhibited in CMT93 cells
      by overexpression of bcl-2, hsp was also induced. Furthermore, when cDNA encoding
      hsp70 was stably transfected into B16 and CMT93 cells, its expression
      significantly enhanced the immunogenicity of both tumors. Increased levels of
      hsp, induced by non-apoptotic cell killing, may provide an immunostimulatory
      signal in vivo which helps break tolerance to tumor antigens. These findings have
      important implications for the development of novel anti-cancer therapies aimed
      at promoting patients' immune responses to their own tumors.

PMID- 9585233
TI  - Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO
      1/Fas) mediated apoptosis.
AB  - Wilson's disease can result in fulminant liver failure due to hepatic copper
      overload. The CD95 system mediates apoptosis and has been demonstrated to be
      involved in liver disease. In this study CD95 mediated apoptosis was investigated
      in patients with fulminant hepatic failure in the course of Wilson's disease and
      in an in vitro model of copper treated human hepatoma cells. In patients, hepatic
      expression of CD95 and CD95L mRNA and apoptosis were detected. Copper overload in
      vitro resulted in hepatocytic apoptosis which could be reduced with a
      neutralizing anti-CD95L antibody. Copper treatment of hepatocytes results in
      activation of the CD95 system and induction of apoptosis which is operative
      during the course of hepatic failure in acute Wilson's disease.

PMID- 9585234
TI  - Eradication of established murine tumors using a novel cell-free vaccine:
      dendritic cell-derived exosomes.
AB  - Dendritic cells (DCs) are professional antigen presenting cells with the unique
      capacity to induce primary and secondary immune responses in vivo. Here, we show
      that DCs secrete antigen presenting vesicles, called exosomes, which express
      functional Major Histocompatibility Complex class I and class II, and T-cell
      costimulatory molecules. Tumor peptide-pulsed DC-derived exosomes prime specific
      cytotoxic T lymphocytes in vivo and eradicate or suppress growth of established
      murine tumors in a T cell-dependent manner. Exosome-based cell-free vaccines
      represent an alternative to DC adoptive therapy for suppressing tumor growth.

PMID- 9585235
TI  - Characterization of a recombinant plant monoclonal secretory antibody and
      preventive immunotherapy in humans.
AB  - A functional comparison was made between a monoclonal secretory antibody
      generated in transgenic plants and its parent murine IgG antibody.The affinity
      constants of both antibodies for a Streptococcus mutans adhesion protein were
      similar. However the secretory antibody had a higher functional affinity due to
      its dimeric structure. In the human oral cavity, the secretory antibody survived
      for up to three days, compared with one day for the IgG antibody. The plant
      secretory antibody afforded specific protection in humans against oral
      streptococcal colonization for at least four months. We demonstrate that
      transgenic plants can be used to produce high affinity, monoclonal secretory
      antibodies that can prevent specific microbial colonization in humans. These
      findings could be extended to the immunotherapeutic prevention of other mucosal
      infections in humans and animals.

PMID- 9585236
TI  - Immunogenicity in humans of a recombinant bacterial antigen delivered in a
      transgenic potato.
AB  - Compared with vaccine delivery by injection, oral vaccines offer the hope of more
      convenient immunization strategies and a more practical means of implementing
      universal vaccination programs throughout the world. Oral vaccines act by
      stimulating the immune system at effector sites (lymphoid tissue) located in the
      gut. Genetic engineering has been used with variable success to design living and
      non-living systems as a means to deliver antigens to these sites and to stimulate
      a desired immune response. More recently, plant biotechnology techniques have
      been used to create plants which contain a gene derived from a human pathogen;
      the resultant plant tissues will accumulate an antigenic protein encoded by the
      foreign DNA. In pre-clinical trials, we found that antigenic proteins produced in
      transgenic plants retained immunogenic properties when purified; if injected into
      mice the antigen caused production of protein-specific antibodies. Moreover, in
      some experiments, if the plant tissues were simply fed to mice, a mucosal immune
      response occurred. The present study was conducted as a proof of principle to
      determine if humans would also develop a serum and/or mucosal immune response to
      an antigen delivered in an uncooked foodstuff.

PMID- 9585237
TI  - Treatment of chronic hepadnavirus infection in a woodchuck animal model with an
      inhibitor of protein folding and trafficking.
AB  - A novel strategy for anti-viral intervention of hepatitis B virus (HBV) through
      the disruption of the proper folding and transport of the hepadnavirus
      glycoproteins is described. Laboratory reared woodchucks chronically infected
      with woodchuck hepatitis virus (WHV) were treated with N-nonyl-deoxynojirimycin
      (N-nonyl-DNJ), an inhibitor of the endoplasmic reticulum (ER) alpha-glucosidases.
      The woodchucks experienced significant dose dependent decreases in enveloped WHV,
      resulting in undetectable amounts in some cases. The reduction in viremia
      correlated with the levels of hyperglucosylated glycan in the serum of treated
      animals. This correlation supports the mechanism of action associated with the
      drug and highlights the extreme sensitivity of the virus to this type of glycan
      inhibitor. At N-nonyl-DNJ concentrations that prevented WHV secretion, the
      glycosylation of most serum glycoproteins appeared unaffected, suggesting great
      selectivity for this class of therapeutics. Indeed, this may account for the low
      toxicity of the compound over the treatment period. We provide the first evidence
      that glucosidase inhibitors can be used in vivo to alter specific steps in the N
      linked glycosylation pathway and that this inhibition has anti-viral effects.

PMID- 9585238
TI  - Mice lacking neutrophil elastase reveal impaired host defense against gram
      negative bacterial sepsis.
AB  - Neutrophil elastase (NE) is a potent serine proteinase whose expression is
      limited to a narrow window during myeloid development. In neutrophils, NE is
      stored in azurophil granules along with other serine proteinases (cathepsin G,
      proteinase 3 and azurocidin) at concentrations exceeding 5 mM. As a result of its
      capacity to efficiently degrade extracellular matrix, NE has been implicated in a
      variety of destructive diseases. Indeed, while much interest has focused on the
      pathologic effects of this enzyme, little is known regarding its normal
      physiologic function(s). Because previous in vitro data have shown that NE
      exhibits antibacterial activity, we investigated the role of NE in host defense
      against bacteria. Generating strains of mice deficient in NE (NE-/-) by targeted
      mutagenesis, we show that NE-/- mice are more susceptible than their normal
      littermates to sepsis and death following intraperitoneal infection with Gram
      negative (Klebsiella pneumoniae and Escherichia coli) but not Gram positive
      (Staphylococcus aureus) bacteria. Our data indicate that neutrophils migrate
      normally to sites of infection in the absence of NE, but that NE is required for
      maximal intracellular killing of Gram negative bacteria by neutrophils.

PMID- 9585239
TI  - Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin
      syndrome.
AB  - Gorlin (or nevoid basal cell carcinoma) syndrome is characterized by a variety of
      clinical problems including generalized overgrowth of the body, cysts,
      developmental abnormalities of the skeleton and a predisposition to benign and
      malignant tumors. The syndrome results from germline mutations of the human
      homolog of the drosophila segment polarity gene patched (ptc). Here we report
      that mice heterozygous for ptc develop many of the features characteristic of
      Gorlin syndrome and that they exhibit a high incidence of rhabdomyosarcomas
      (RMS), the most common soft-tissue sarcoma in children. The downstream signalling
      partner of ptc, gli1, was overexpressed in all RMSs analyzed, indicating that
      abnormal signalling of the ptc-gli1 pathway may be common for the various tumors
      associated with the syndrome. igf2, implicated in the formation of RMSs, was also
      overexpressed, suggesting cross-talk between the ptc and igf2 pathways in
      tumorigenesis. Developmental defects in Gorlin syndrome resemble those induced by
      ionizing radiation. We show that ptc heterozygous mice exhibit increased
      incidence of radiation-induced teratogenesis. This suggests a role for ptc in the
      response to ionizing radiation and provides a model for both the systemic
      (developmental) and stochastic (cancer) abnormalities observed in Gorlin
      syndrome.

PMID- 9585240
TI  - Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic
      resonance imaging.
AB  - Angiogenesis, the formation of new blood vessels, is a requirement for malignant
      tumor growth and metastasis. In the absence of angiogenesis, local tumor
      expansion is suppressed at a few millimeters and cells lack routes for distant
      hematogenous spread. Clinical studies have demonstrated that the degree of
      angiogenesis is correlated with the malignant potential of several cancers,
      including breast cancer and malignant melanoma. Moreover, the expression of a
      specific angiogenesis marker, the endothelial integrin alphaVbeta3, has been
      shown to correlate with tumor grade. However, studies of tumor angiogenesis such
      as these have generally relied on invasive procedures, adequate tissue sampling
      and meticulous estimation of histologic microvessel density. In the present
      report, we describe a novel approach to detecting angiogenesis in vivo using
      magnetic resonance imaging (MRI) and a paramagnetic contrast agent targeted to
      endothelial alphaVbeta3 via the LM609 monoclonal antibody. This approach provided
      enhanced and detailed imaging of rabbit carcinomas by directly targeting
      paramagnetic agents to the angiogenic vasculature. In addition, angiogenic 'hot
      spots' not seen by standard MRI were detected. Our strategy for MR imaging of
      alphaVbeta3 thus represents a non-invasive means to assess the growth and
      malignant phenotype of tumors.

PMID- 9585241
TI  - B cells inhibit induction of T cell-dependent tumor immunity.
AB  - Cytotoxic T lymphocyte (CTL) mediated tumor immunity against major
      histocompatibility antigen (MHC) class I-positive but class II-negative tumors
      often requires help from CD4+ T cells. These CD4 cells are activated by MHC class
      II-positive cells that present tumor derived antigens. Considering that different
      antigen presenting cells, such as B cells, macrophages and dendritic cells
      compete for antigen and influence the outcome of an immune response, we analyzed
      tumor immunity in B cell-deficient mice. These mice appear normal with regard to
      T cell immunity and tolerance to some pure foreign antigens. We show here that
      the low immunogenicity of tumors is caused by B cells whose presence in the
      priming phase results in disabled CD4+ T cell help for CTL mediated tumor
      immunity. Instead, in the presence of B cells, a non-protective humoral immune
      response is induced. Our results may explain the enigmatic observation that tumor
      reactive antibodies occur frequently in cancer patients.

PMID- 9585242
TI  - Fluorescent viral vectors: a new technique for the pharmacological analysis of
      gene therapy.

PMID- 9585243
TI  - Mouse models of Hermansky Pudlak syndrome: a review.
AB  - Hermansky Pudlak Syndrome (HPS) is a recessively inherited disease affecting the
      contents and/or the secretion of several related subcellular organelles including
      melanosomes, lysosomes, and platelet dense granules. It presents with disorders
      of pigmentation, prolonged bleeding, and ceroid deposition, often accompanied by
      severe fibrotic lung disease and colitis. In the mouse, the disorder is clearly
      multigenic, caused by at least 14 distinct mutations. Studies on the mouse
      mutants have defined the granule abnormalities of HPS and have shown that the
      disease is associated with a surprising variety of phenotypes affecting many
      tissues. This is an exciting time in HPS research because of the recent molecular
      identification of the gene causing a major form of human HPS and the expected
      identifications of several mouse HPS genes. Identifications of mouse HPS genes
      are expected to increase our understanding of intracellular vesicle trafficking,
      lead to discovery of new human HPS genes, and suggest diagnostic and therapeutic
      approaches toward the more severe clinical consequences of the disease.

PMID- 9585244
TI  - Epidermal oxidative stress in vitiligo.
AB  - Epidermal levels of enzymatic and non-enzymatic antioxidants such as superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), vitamin E (Vit
      E), ubiquinol (CoQ10H2), and reduced glutathione (GSH), as well as
      polyunsaturated fatty acids of phospholipids (PL-PUFA), were evaluated in the
      affected epidermis of 15 patients with active vitiligo (AVP) and in the
      corresponding epidermis of 15 healthy phototype matched controls. The epidermal
      levels of CoQ10H2, Vit E, GSH, and CAT activity were significantly reduced in AVP
      and were associated with a marked increase of oxidized glutathione, whereas SODs
      and GSH-Px activities and ubiquinone concentration remained similar to control
      values. Antioxidant deficiency, in particular the decline of lipophilic
      antioxidants, i.e., CoQ10H2 and Vit E, accounts well for PL-PUFA reduction
      observed in vitiligo epidermis, mainly affecting C18:3 n-3, C20:3 n-6, C20:4 n-6,
      and C22:6 n-3 fatty acids and suggesting the occurrence of a lipoperoxidative
      process. In conclusion, both an imbalance of the intracellular redox status and a
      significant depletion of enzymatic and non-enzymatic antioxidants feature the
      epidermis of AVP, and represent a fingerprint of an abnormal oxidative stress
      leading to epidermal cell injury.

PMID- 9585245
TI  - Comparison of high performance liquid chromatography and stereological image
      analysis for the quantitation of eumelanins and pheomelanins in melanoma cells.
AB  - The aim of the study was to compare two methods quantifying eumelanins and
      pheomelanins, pigments synthesized by melanocytes. One is based on the high
      performance liquid chromatography (HPLC) quantitation of specific degradation
      products of each melanin type. The other requires image analysis, transmission
      electron microscopy (TEM), and stereology. This study was carried out in cultured
      human melanoma cells and for each line, melanins were measured by HPLC and cells
      were fixed and embedded as pellets for TEM. Ultrathin sections were treated or
      not by the alkali elution method allowing the elimination of pheomelanins. The
      obtained micrographs were analyzed with our image analysis program permitting the
      estimation of several primary parameters. Stereology was used for estimating
      melanosomal maturation, intracellular melanins content, and number of melanized
      melanosomes per cell, for total melanin, eumelanins, or pheomelanins. Our results
      show a good correlation between both methods for total melanin, particularly when
      using the cytoplasmic volume density of melanin (r=0.93). Moreover, we report
      that the number of melanized melanosomes per cell and not the melanosomal
      maturation is responsible for the differences in total melanin content observed
      between the different cell lines. However, none of the stereological melanization
      parameters was correlated in the case of eumelanins or pheomelanins. In order to
      demonstrate the utter relevancy of this stereological approach, utilization of
      more pigmented melanoma cells, comparative study of HPLC and stereology, in
      normal epidermal melanocytes and a new evaluation of the alkali elution method in
      appropriate animal models would help us to explain the present results.

PMID- 9585246
TI  - Tyrosinase kinetics: failure of acceleration in oxidation of ring-blocked
      monohydric phenol substrate.
AB  - When 2,5,6-trimethyl-4-hydroxyanisole is used as substrate for mushroom
      tyrosinase the oxidation rate is slow and the kinetics do not exhibit an initial
      acceleration (lag period), in contrast to the kinetics of oxidation of the parent
      compound, 4-hydroxyanisole. This finding is interpreted as evidence that the
      acceleration of oxidation of 4-hydroxyanisole is indirectly contingent on a
      reductive nucleophile addition to the orthoquinone product of the monohydric
      phenol, which is prevented by ring methylation. Such a view is consistent with
      the proposal that the lag-phase characteristic of the kinetics of monohydric
      phenol oxidation by tyrosinase is due to the activation of previously inactive
      enzyme by electron donation from an orthodiphenol substrate formed from the
      orthoquinone oxidation product.

PMID- 9585247
TI  - Production of melanins by ceruloplasmin.
AB  - It was shown that ceruloplasmin, apart from the known oxidative conversion of
      dopamine into melanin, can also produce (DHI)-melanin from 5,6-dihydroxyindole
      and THP-melanin from tetrahydropapaveroline. Ceruloplasmin acts as an oxidase and
      the kinetic parameters for these oxidative reactions are reported. Since these
      ceruloplasmin-catalyzed reactions occur also at pH 7.4, they could have a
      significant physiological impact. This ceruloplasmin-oxidasic activity is
      enhanced by copper ions and inhibited by chelators, such as
      ethylenediaminetetraacetic acid (EDTA) and desferoxamine (DEF). Some possible
      implication of melanin production in blood are discussed.

PMID- 9585248
TI  - Cultures of skin fragments of Salamandra salamandra salamandra (L.) larvae.
AB  - As part of a study on the pigmentary system of Salamandra salamandra salamandra
      (L.), we cultured skin fragments of 7-10-day-old larvae in order to examine the
      expression of molecules implicated in cellular adhesion and migration and in
      regulating cell-cell relationships. Keratinocytes, fibroblasts, Leydig cells,
      xanthophores, and melanophores migrated from the fragments and were observed in
      the outgrowth. Keratinocytes and fibroblasts organized into an epidermal layer
      and an underlying "dermal portion." The chromatophores were always located below
      the epithelial cells, often with fibroblasts. We examined by immunocytochemistry
      the expression of fibronectin, beta1-integrin, L-CAM, and A-CAM in the cultures.
      Many keratinocytes, fibroblasts, and Leydig cells expressed all the signal
      molecules tested. Xanthophores and melanophores were only immunoreactive to the
      anti-adhesion molecules antisera. Since the molecules tested are known to play a
      role in cell adhesion, growth, and spreading, as well as in regulating tissue
      differentiation and in maintaining normal tissue morphology, we may hypothesize
      that in Salamandra salamandra salamandra fibronectin, beta1-integrin, L-, and A
      CAMs concertedly act to stabilize the architecture of the outgrowth and regulate
      the relationships between chromatophores and those between chromatophores and the
      other elements of the skin culture.

PMID- 9585249
TI  - The role of melanocytes in the repair of UV related DNA damage in keratinocytes.
AB  - Epidermal pigmentation and UV exposure are related to the incidence of skin
      tumors. There is a higher incidence of UV related skin tumors in populations with
      low pigment and in vitiligo patients, resulting from DNA damage. Normally DNA
      repair processes set in with the expression of PCNA in the keratinocyte. The
      present study was conducted on the marginal zone skin in vitiligo. Whole skin
      organ cultures irradiated with increasing doses of UV in the 280400 nm range show
      that in the depigmented area there is no expression of PCNA by the keratinocytes.
      In comparison, the marginal zone keratinocytes show a dose related positivity in
      the presence of UV responsive melanocytes. These photoresponsive melanocytes show
      dendricity and cytoplasmic PCNA positivity. The melanocytes interact with
      keratinocytes by active melanosome transfer. From this study it is suggested that
      this involves transfer of PCNA as well. The present study indicates the
      differentiating keratinocytes in skin do not express PCNA but appear to be
      dependent on active UV responding melanocytes for DNA repair. This factor could
      play an important role in the occurrence of UV-related skin tumors.

PMID- 9585250
TI  - In vitro culture of melanomacrophages from the spleen and liver of turtles:
      comments on melanomacrophage morphology.
AB  - Melanomacrophages were extracted and cultured from the spleen and liver of three
      turtle species representing three divergent families, the Chelydridae, Emydidae,
      and Trionychidae. Homogeneous cultures were obtained by repeatedly forcing
      minced, frequently washed tissue through a sterile screen and separating the
      resulting cells by centrifugation. The cells were surprisingly resistant to lysis
      and were maintained in culture for over 12 weeks where culture characteristics,
      appearance, and longevity from these two organs were similar. They attached to
      the T flask substrate as individual cells and aggregates and spread out 14 days
      after being placed in media. Ridges and ruffles at the distal ends of pseudopodia
      and the cell surface along with a zone of clearing attest to the cells'
      phagocytic nature. A few melanomacrophages from both organs underwent mitosis 14
      days after treatment with granulocyte macrophage colony-stimulating factor but it
      is possible that other factors contributed to stimulation of cell division.

PMID- 9585251
TI  - Chemical degradation of melanins: application to identification of dopamine
      melanin.
AB  - Melanocytes produce two chemically distinct types of melanin pigments, eumelanins
      and pheomelanins. These pigments can be quantitatively analyzed by acidic KMnO4
      oxidation or reductive hydrolysis with hydriodic acid (HI) to form pyrrole-2,3,5
      tricarboxylic acid (PTCA) or aminohydroxyphenylalanine (AHP), respectively. Dark
      brown melanin-like pigments are also widespread in nature, for example, in the
      substantia nigra of humans and primates (neuromelanin), in butterfly wings and in
      the fungus Cryptococcus neoformans. To characterize such diverse types of
      melanins, we have improved the alkaline H2O2 oxidation method of Napolitano et
      al. (Tetrahedron, 51:5913-5920, 1995) and re-examined the HI hydrolysis method of
      Wakamatsu et al. (Neurosci. Lett., 131:57-60, 1991). The results obtained with
      H2O2 oxidation show that 1) pyrrole-2,3-dicarboxylic acid (PDCA), a specific
      marker of 5,6-dihydroxyindole units in melanins, is produced in yields ten times
      higher than by acidic KMnO4 oxidation, and 2) PTCA is artificially produced from
      pheomelanins. The results with HI hydrolysis show that dopamine-melanin produces
      a 1:1 mixture of 3-amino and 4-amino isomers of aminohydroxyphenylethylamine,
      while the isomer ratio is about 0.2 in melanins prepared from dopamine and
      cysteine. These results indicate that alkaline H2O2 oxidation is useful in
      characterizing synthetic and natural eumelanins and that reductive hydrolysis
      with HI can be applied to analyzing oxidation products of dopamine such as
      neuromelanin.

PMID- 9585252
TI  - Involvement of tyrosine phosphorylation of p185(c-erbB2/neu) in tumorigenicity
      induced by X-rays and the neu oncogene in human breast epithelial cells.
AB  - Ionizing radiation is the exogenous agent best proven to induce breast cancer. c
      erbB2/neu amplification and overexpression are known to occur in breast cancer
      and are correlated with aggressive tumor growth and poor prognosis. We have
      developed simian virus 40-immortalized cell lines from normal human breast
      epithelial cells (HBECs) with luminal and stem-cell characteristics. In this
      study, we examined whether x-rays and a mutated neu oncogene are capable of
      inducing tumorigenicity in these cells. The results indicated that x-rays were
      effective in converting immortal non-tumorigenic HBECs to weakly tumorigenic
      cells that then could be transformed to highly tumorigenic cells by the neu
      oncogene. The in vitro growth of these tumorigenic cells was significantly faster
      than that of the parental non-tumorigenic cells in growth factor- and hormone
      supplemented or -depleted media. The neu oncogene, however, had no tumorigenic
      effect on immortal non-tumorigenic cells. The expression of p185(c-erb82/neu) was
      elevated in neu-transduced immortal or weakly tumorigenic cell lines. However,
      only in the latter was p185(c-erbB2/neu) found to be phosphorylated at tyrosine
      residues. Thus, x-rays appear to induce a genetic alteration that confers weak
      tumorigenicity on immortal HBECs and interacts with p185(c-erbB2/neu) directly or
      indirectly to give rise to fast-growing tumors.

PMID- 9585253
TI  - Activation of tissue-factor gene expression in breast carcinoma cells by
      stimulation of the RAF-ERK signaling pathway.
AB  - Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the
      extrinsic pathway of coagulation. The overexpression of TF in human malignancy
      has been correlated with the angiogenic phenotype, poor prognosis, and
      thromboembolic complications. The mechanisms underlying constitutive expression
      of TF in cancer cells are poorly defined. We cloned TF cDNA on the basis of its
      strong expression in metastatic MDA-MB-231 breast carcinoma cells in contrast to
      its weak expression in non-metastatic MCF-7 cells. Transient transfection
      analysis showed that TF promoter activity in MCF-7 cells could be stimulated by
      expression of a membrane-targeted raf kinase (raf-CAAX). raf-induced activity was
      dependent on the presence of an AP-1/NF-kappaB motif in the TF promoter and was
      inhibited by dominant-negative mutants of jun and by I-kappaB alpha. MDA-MB-231
      cells were found to contain higher levels of ERK1/2 kinase activity than did MCF
      7 cells. Electrophoretic mobility shift assays showed that MDA-MB-231 nuclear
      proteins bound strongly to an oligonucleotide corresponding to the AP-1/NF-kappaB
      sequence, whereas MCF-7 nuclear extracts showed weak binding to this element.
      Finally, we showed that TF mRNA levels in MDA-MB-231 cells declined after
      addition of the mitogen-activated protein kinase kinase inhibitor PD98059. Our
      data showed that activation of the raf-ERK pathway led to activation of TF
      expression in breast carcinoma cells and suggested that constitutive activation
      of this pathway leads to high TF expression in MDA-MB-231 cells.

PMID- 9585254
TI  - Induction of transgene expression in Tg.AC(v-Ha-ras) transgenic mice concomitant
      with DNA hypomethylation.
AB  - Tg.AC transgenic mice have a transgene composed of a zeta-globin transcriptional
      control region, a v-Ha-ras coding region, and a simian virus 40 3'
      polyadenylation signal sequence. Induced ectopic expression of the transgene by
      chemical treatment or full-skin-thickness wounding leads to the development of
      skin papillomas. Reverse transcription-polymerase chain reaction assays and
      protein blotting indicated that the transgene was expressed 16-28 d after full
      skin-thickness surgical wounding. Normal unwounded skin did not express the
      transgene. DNA blotting indicated that the position of the transgene remained
      stable during wound-induced tumorigenesis. Concomitant with the v-Ha-ras mRNA and
      protein expression was the hypomethylation of specific MspI/HpaII sites within
      the transgene. These results are consistent with the hypothesis that
      hypomethylation is required for the induced and sustained expression of the Tg.AC
      v-Ha-ras transgene in spontaneous and induced tumors in Tg.AC mice.

PMID- 9585255
TI  - Ki-ras gene mutations and absence of p53 gene mutations in spontaneous and
      urethane-induced early lung lesions in CBA/J mice.
AB  - Ki-ras and p53 genes are involved in human lung carcinogenesis; however, the role
      of these genes in experimental lung tumors is not well known. In our study, the
      CBA/J mouse strain was used to investigate the presence of Ki-ras and p53
      alterations in lung carcinogenesis of spontaneous tumors and tumors induced with
      high and low doses of urethane (ethyl carbamate). To study the presence of these
      alterations in the early stages of lung carcinogenesis and in very small lung
      tumors, restriction fragment length polymorphism and single-strand conformation
      polymorphism analyses were performed on polymerase chain reaction-amplified DNA
      from microdissected tumoral and normal lung samples. Ki-ras gene mutations in
      codons 12 and 61 were detected in all types of lung lesions, even in small and
      preneoplastic lesions, and their incidence increased with progression from lung
      hyperplasias (18%) to adenomas (75%) and to carcinomas (80%). Urethane exposure,
      in both high and low doses, increased the incidence of Ki-ras mutations in lung
      tumors, especially in adenomas. The presence of Ki-ras gene mutations in very
      small urethane-induced lung tumors and the absence of hyperplasias among the
      treated-group lesions may indicate that urethane accelerates tumoral progression.
      No p53 mutations were detected in exons 5-8 in any of the epithelium-derived lung
      tumors. Only one p53 mutation in exon 5 was found in a spontaneous lymphoma.
      Therefore, p53 mutations do not seem to cooperate with Ki-ras gene mutations or
      represent an alternative molecular pathway in murine carcinogenesis.

PMID- 9585256
TI  - Characterization of human epidermal growth factor receptor and c-Src interactions
      in human breast tumor cells.
AB  - In C3H/10T1/2 murine fibroblasts, overexpression of both c-Src and the human
      epidermal growth factor (EGF) receptor 1 (HER1) is required for detection of
      stable complexes between the two molecules and results in hyperactivation of the
      receptor and synergistic increases in tumor formation in nude mice, as compared
      with cells that overexpress only one of the pair. Elevated levels or activities
      of c-Src and HER1 also occur in a subset of later-stage breast cancers,
      suggesting that interactions between these two molecules could contribute to a
      more aggressive clinical course. To determine whether stable complexes between c
      Src and HER1 occur in human breast cancers under the same conditions as in murine
      fibroblasts and whether the appearance of such complexes correlates with enhanced
      signaling through the EGF receptor and increased tumor growth, human breast tumor
      cell lines and tumor tissues were analyzed for a number of c-Src/HER1-mediated
      signaling events and tumorigenicity. In a panel of 14 cell lines, 10
      overexpressed c-Src, and of these, five contained elevated levels of HER1 and
      exhibited an EGF-dependent association between HER1 and c-Src. This association
      was also present in a HER1/c-Src-overexpressing tumor sample from a breast cancer
      patient. Further analysis of signaling events revealed that phosphorylation of
      the HER1 substrate, Shc, and its downstream effector, mitogen-activated protein
      kinase, was increased in EGF-stimulated MDA-MB-468, MDA-MB-231, and BT-549 cells
      (which overexpress both c-Src and HER1) as compared with MCF7 and ZR-75-1 cells
      (which only overexpress c-Src). Furthermore, MDA-MB-468 and MDA-MB-231 cells
      displayed increased tumorigenicity in nude mice. These results support the
      hypothesis that c-Src/HER1 interactions contribute to tumor progression in
      certain late-stage breast tumor cells.

PMID- 9585257
TI  - Induction of mutual stabilization and retardation of tumor growth by coexpression
      of plakoglobin and E-cadherin in mouse skin spindle carcinoma cells.
AB  - The influence of plakoglobin on the phenotype and tumorigenicity of murine
      spindle carcinoma cells was analyzed by stable transfection of plakoglobin cDNA
      in the presence or absence of E-cadherin expression. In either situation,
      overexpression of plakoglobin was unable to modify the fibroblastic phenotype or
      to completely suppress the tumorigenic behavior of the spindle cells, but a
      moderate reduction in the growth rate of the tumors was induced by plakoglobin
      and was further enhanced by E-cadherin. Coexpression of E-cadherin and
      plakoglobin induced a mutual stabilization, increasing the half-life of both
      molecules in the double transfectants more than 5- and 30-fold, respectively,
      with a turnover rate similar to that observed in control keratinocytes. The
      stabilization of E-cadherin, as well as that of plakoglobin, was maintained in
      the tumors induced by the double transfectants, in contrast to the unstable
      expression of E-cadherin observed in tumors induced in plakoglobin-deficient
      cells. The E-cadherin/catenin complexes present in the double transfectants were
      functional in calcium-dependent aggregation assays and similar in composition to
      those of control keratinocytes. However, most of the components of the complexes
      of the transfectants were solubilized by non-ionic detergents, indicating a weak
      interaction with the actin cytoskeleton. These results indicated that restoration
      of E-cadherin/catenin complexes was not sufficient to induce the transition of
      the fibroblastic cells to an epithelial phenotype or to completely suppress the
      tumorigenicity of mouse skin spindle carcinoma cells.

PMID- 9585259
TI  - Micronuclei and developmental abnormalities in 4-day mouse embryos after paternal
      treatment with acrylamide.
AB  - The developmental consequences of paternal exposure to acrylamide (50 mg/kg i.p.
      for 5 days) were assessed in preimplantation embryos. There was a significant
      increase in the proportion of morphologically abnormal embryos after postmeiotic
      treatment during spermatogenesis (88.7% vs. 14.8% in control). Abnormal embryos
      had an average of 1.8 +/- 3.5 cells and > 80% had at least one fragmented
      nucleus. In addition, morphologically normal embryos were significantly delayed
      (34.3 +/- 12.8 cells per embryo vs. 57.6 +/- 15.7 in control, P < 0.001).
      Acrylamide caused 10- and 20-fold increases in frequencies of cells with
      micronuclei (MN) in morphologically normal and abnormal embryos, respectively (41
      and 93 MN per 1,000 cells). Both centromere-negative (MN-) and centromere
      positive (MN+) were induced. Nuclei of abnormal embryos were significantly larger
      (900 microm2 vs. 250 microm2) than controls. In addition, MN of abnormal embryos
      were larger than those of normal embryos (21.2 microm2 vs. 6.5 microm2, P <
      0.01). Among control embryos, MN+ were significantly larger than MN- (P < 0.05).
      These findings suggest that the preimplantation embryo is a sensitive indicator
      of paternally transmitted effects on early development. Multiple mechanisms
      appear to be involved, including cytogenetic damage, proliferation arrest/delay,
      and fertilization failure. Future studies are needed to establish how induced
      cytological defects in preimplantation embryos contribute to birth defects and
      other postimplantation abnormalities.

PMID- 9585258
TI  - Formation and repair of DNA lesions in the p53 gene: relation to cancer
      mutations?
AB  - The number and diversity of mutations in the p53 mutation data base provides
      indirect evidence that implicates environmental mutagens in human carcinogenesis.
      The p53 gene has a large mutational target size; more than 280 out of 393 amino
      acids are found mutated in tumors. We argue that there is possibly a limited
      involvement of selection for specific mutations in the central domain of the
      protein, and that the distribution of DNA damage along the p53 gene caused by
      environmental carcinogens can be correlated with the mutational spectra, i.e.,
      hotspots and types of mutations, of certain cancers. This concept has been
      validated by experiments with sunlight and the cigarette smoke component
      benzo[a]pyrene representing the polycyclic aromatic hydrocarbon class of
      carcinogens. The damage/repair data obtained for these mutagens can predict
      certain parameters of the mutational spectra including the distribution of
      hotspots in human nonmelanoma skin cancers and lung cancers from smokers. Future
      studies with suspected mutagens may help to implicate causative agents involved
      in other cancers, such as colon and breast cancer, where the exact carcinogen has
      not yet been identified but an environmental factor is suspected.

PMID- 9585260
TI  - Sister chromatid exchange and micronucleus frequency in human lymphocytes of
      1,650 subjects in an Italian population: I. Contribution of methodological
      factors.
AB  - The influence of several methodological factors on mean values of sister
      chromatid exchanges (SCEs) and micronuclei (MN) in peripheral lymphocytes of
      1,650 subjects was analyzed. Donors belonged to a general healthy population
      living in Pisa and in two nearby small cities: Cascina and Navacchio (Ca-Na).
      Blood samples were collected over a period of 29 months and processed in three
      different laboratories of the some institute. Slides were analyzed by several
      scorers. Our data showed that lymphocyte proliferation indexes (PIs) and baseline
      mean values of SCEs were affected mainly by sampling period. This factor
      accounted for a percentage ranging from roughly 10% (Pisa) to 20% (Ca-Na) of
      total SCE variance and from roughly 10% (Pisa) to 13% (Ca-Na) of total PIs
      variance. A marginal effect was attributable to the different laboratories
      involved (maximum 3% for SCEs and 7% for PIs). The sampling period variable
      included many sources of variability such as culture media batches, fetal calf
      serum, PHA, BrdUrd, and seasonality. MN counts revealed a more marked dependence
      on processing laboratories. This factor accounted for a percentage of roughly 10%
      (Pisa and Ca-Na) of total variance, while the sampling period was marginally
      effective (about 1-4% of total variability). Because laboratories were equipped
      and supplied with the same materials and consumables and technicians were rotated
      constantly, the only variable ascertained was represented by the three different
      models of CO2 incubators used for lymphocyte culturing. When "month" and
      "incubator" variables were considered jointly, experimental variability accounted
      for 15-20% of total variance, both for PIs and mean values SCEs and MN. The
      variability due to slide scoring was reduced by assigning each slide to five
      different scorers and matching low with high scorers in each group. Present data
      show that when the study is performed under these controlled conditions, about
      20% of total interdonor variability can be explained by experimental or seasonal
      factors.

PMID- 9585261
TI  - Sister chromatid exchange and micronucleus frequency in human lymphocytes of
      1,650 subjects in an Italian population: II. Contribution of sex, age, and
      lifestyle.
AB  - Sister chromatid exchange (SCE) and micronuclei (MN) analysis was carried out on
      1,650 healthy individuals living in Pisa and in two nearby small cities, Cascina
      and Navacchio (Ca-Na). The effect of smoking on SCEs was linearly correlated with
      the number of cigarettes per day, and an increase of 7.3% SCEs was detectable for
      as few cigarettes as 1-10/day. Ex-smokers showed intermediate mean values of SCEs
      (8.09 +/- 1.88) in comparison with never smokers (7.54 +/- 1.61) and current
      smokers (8.45 +/- 1.94). Mean values of SCEs of ex-smokers decreased linearly
      with time of smoking cessation, reaching the mean values of never smokers within
      8 years. The extent of SCE decrease was inversely proportional to the number of
      cigarettes previously smoked. No interaction between smoking habits and coffee or
      alcohol drinking on SCEs was observed. A borderline (P = 0.053) increase in mean
      SCE values in coffee drinkers (more than 3 cups/day) was found. The age effect on
      SCEs was remarkable in Ca-Na, but not in Pisa donors. Job type was not associated
      with significant modification of mean values of SCEs. Multiple logistic
      regression analysis revealed a statistically significant association between the
      proportion of high frequency cells (HCF) outliers and coffee consumption. Age and
      sex appeared to be by far the most important variables associated with
      modifications in MN frequency, which increased by 0.04 per thousand and 0.02 per
      thousand per year in males and females, respectively. Children and young donors
      (age < or = 40 years) showed lower MN frequency regardless of sex, whereas sex
      appeared to determine a significantly higher increase of MN only in females older
      than 40 years. In contrast, in males the MN rate by age tended to level off after
      the age of 30-50. MN frequencies of Pisa blue- and white-collar workers were
      statistically significantly higher than in students (+0.71 and +0.55 per
      thousand, respectively). Smoking did not determine any increase of MN frequency.
      A total lack of correlation (P = 0.913) between MN and SCEs was observed.

PMID- 9585262
TI  - Mutational response at the splenic T-lymphocyte hprt locus in mice treated as
      neonates: contrasting effects of the carcinogens N-ethyl-N-nitrosourea,
      dimethylnitrosamine, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
AB  - The newborn mouse tumorigenicity assay, which involves the treatment of animals
      during the first two weeks after birth and monitoring tumor induction after a
      year, has been suggested as a cost- and time-effective alternative to the
      conventional two-year rodent bioassay. In order to evaluate whether or not
      lymphocyte hprt mutant induction is an accurate predictor of carcinogenicity in
      the assay, we determined the frequencies of 6-thioguanine-resistant (TGr)
      lymphocytes in the spleens of mice neonatally treated with the carcinogenic
      mutagens N-ethyl-N-nitrosourea (ENU), dimethylnitrosamine (DMN), and 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Male C57BL/6 pups were injected on
      postnatal days 8 and 15, and the frequency of TGr T-lymphocytes was measured in
      groups of three animals, sacrificed periodically up to 31 weeks post-treatment.
      Compared to background frequencies of 1.1-2.9 x 10(-6), mutant frequencies (MFS)
      reached 155.1 x 10(-6) following a cumulative dose of 49 mg ENU/kg body weight
      and 172.3 x 10(-6) following a cumulative dose of 142 mg ENU/kg. These results
      show that TGr lymphocyte mutations can be induced and measured in mice treated as
      neonates and that the induced MFs found for mice treated neonatally with ENU are
      comparable with frequencies reported for the treatment of adult animals with the
      same chemical. In contrast, treatment with the promutagenic and procarcinogenic
      compounds DMN (at a maximum concentration of 10.5 mg/kg) and PhIP (26.2 mg/kg)
      did not result in an increase in lymphocyte MF, suggesting that reactive
      metabolites of these compounds may not be reaching cells that are sensitive for
      mutation fixation. The results indicate that the lymphocyte hprt assay may fail
      to predict the carcinogenicity of some test chemicals in the neonatal mouse
      bioassay.

PMID- 9585263
TI  - Long-term mutagenicity studies with chloroform and dimethylnitrosamine in female
      lacI transgenic B6C3F1 mice.
AB  - The weight of evidence indicates that chloroform induces cancer in the female
      B6C3F1 mouse liver via a nongenotoxic-cytotoxic mode of action. However, it is
      probable that DNA damage occurs secondary to events associated with cytolethality
      and regenerative cell proliferation. The purpose of the present study was to
      evaluate the potential mutagenic activity of chloroform in the B6C3F1 lacI
      transgenic mouse liver mutagenesis assay including mutagenic events that might
      occur secondary to cytolethality. The positive control, dimethylnitrosamine (DMN)
      is a DNA-reactive mutagen and carcinogen. DMN-induced mutations were anticipated
      to require only a brief exposure and without further treatment were predicted to
      remain unchanged over time at those frequencies. Chloroform-induced mutations
      secondary to toxicity were anticipated to require longer exposure periods and to
      occur only under conditions that produced sustained cytolethality and
      regenerative cell proliferation. Female B6C3F1 lacI transgenic mice were treated
      with daily doses of 2, 4, or 8 mg/kg of DMN by gavage for 4 days and then held
      until analysis 10, 30, 90, and 180 days postexposure. Livers from DMN-treated
      mice exhibited a dose-related 2- to 5-fold increase over control mutant
      frequencies and remained at those levels for 10 through 180 days postexposure.
      Thus, following the initial induction by DMN no selective mutation amplification
      or loss was seen for this extended period of time. Female B6C3F1 lacI mice were
      exposed daily for 6 hr/day 7 days/week to 0, 10, 30, or 90 ppm chloroform by
      inhalation, representing nonhepatotoxic, borderline, or overtly hepatotoxic
      chloroform exposures. Timepoints for determination of lacI mutant frequency were
      10, 30, 90, and 180 days of exposure. No increase in lacI mutant frequency in the
      liver was observed at any dose or timepoint with chloroform, indicating a lack of
      DNA reactivity. DNA alterations secondary to toxicity either did not occur or
      were of a type not detectable by lacI mutant frequency analysis, such as large
      deletions.

PMID- 9585264
TI  - Fluchloralin is cytotoxic and genotoxic and induces apoptosis in mammalian cells.
AB  - The genotoxic and cytotoxic effects of a widely used herbicide, fluchloralin,
      were assessed using cultured mammalian cells. Treatment of cells for 8-12 hr with
      fluchloralin resulted in a significant increase in the frequency of metaphase
      cells with chromosomal damage. At higher concentrations, the herbicide also
      induced an increase in the frequency of sister chromatid exchange. A 50% loss in
      viability was observed when cells were exposed to the herbicide for 72 hr. To
      understand the mechanism of cell death caused by fluchloralin, its effect on DNA
      synthesis and its ability to induce apoptosis were investigated. Even short (6
      hr) treatment of cells with fluchloralin resulted in a 30-50% inhibition of DNA
      synthesis. Agarose gel electrophoresis of DNA from herbicide-treated cells and
      cytochemical staining indicate the induction of apoptosis by fluchloralin.

PMID- 9585265
TI  - Dose-response studies of the induction of hyperdiploidy and polyploidy by
      diethylstilbestrol and 17beta-estradiol in cultured human lymphocytes using
      multicolor fluorescence in situ hybridization.
AB  - Diethylstilbestrol (DES) and 17beta-estradiol (E2) are known inducers of
      aneuploidy and polyploidy in vivo and in vitro. Isolated human lymphocytes were
      treated with the stilbene estrogen DES (0.05-50 microM) and the steroid estrogen
      E2 (0.05-75 microM) in culture. Multicolor fluorescence in situ hybridization
      (FISH) with DNA probes for the centromere and adjacent heterochromatin regions of
      chromosomes 1, 9, and 16 was used to detect hyperdiploidy, polyploidy, and
      chromosomal breakage affecting these chromosomes. Using this FISH technique,
      significant nonlinear increases in hyperdiploidy were observed with both
      compounds, whereas no induction of chromosomal breakage affecting the pericentric
      heterochromatin regions of chromosomes 1, 9, and 16 could be detected. DES
      induced a maximum of approximately 13% hyperdiploid cells at 30 microM, whereas
      E2 showed its highest induction at 75 microM with 7% hyperdiploid cells. To
      distinguish hyperdiploidy from polyploidy, a FISH labeling strategy to detect
      multiple chromosomes simultaneously was established. Using this approach, we
      could show that most of the cells showing multiple hybridization regions after
      treatment with both chemicals were most likely the result of polyploidy rather
      than true hyperdiploidy. These results indicate that the induction of
      hyperdiploidy/polyploidy with DES and E2 show sublinear dose-response
      relationships with likely threshold concentrations in human lymphocytes and that
      FISH with multiple probes targeting different chromosomes can be used to estimate
      hyperdiploidy and polyploidy frequencies.

PMID- 9585266
TI  - Modulation of 2,6-dinitrotoluene genotoxicity by alachlor treatment of Fischer
      344 rats.
AB  - Due to its widespread use as a preemergent herbicide, alachlor has been detected
      as a groundwater contaminant. The procarcinogen, 2,6-dinitrotoluene (DNT), a by
      product of the munitions industry and a precursor to polyurethane production, is
      found in the manufacturing waste stream. This study explores the effect of
      alachlor treatment on the bioactivation of DNT by examining urine mutagenicity,
      intestinal enzymes, and hepatic DNA adducts to detect changes in metabolism. Five
      week-old male rats were treated daily by gavage with 50 mg/kg of alachlor for up
      to 5 weeks while control animals received an equal volume of peanut oil. At 1, 3,
      and 5 weeks following the initial alachlor dose, animals were administered p.o.
      75 mg/kg DNT or DMSO. Urine was collected for 24 hr in metabolism cages.
      Following incubation with sulfatase and beta-glucuronidase, urines were
      individually concentrated by C-18 solid phase extraction, dried under N2, and
      prepared for bioassay in Salmonella typhimurium strain TA98 with and without
      metabolic activation. Urine from peanut oil- and alachlor-treated rots was not
      mutagenic. Even though calf thymus DNA-alachlor adducts formed in vitro, no
      hepatic DNA adducts were detected in vivo in these two treatment groups.
      Interestingly, a significant increase in excretion of mutagenic urine from DNT
      treated rats was observed following 3 weeks of alachlor treatment in the absence
      of S9 (690 +/- 130 vs. 339 +/- 28 revertants/ml) which corresponded to increased
      DNT-related hepatic DNA adduct formation (5.90 +/- 0.88 adducts/10(8) nucleotides
      vs. 10.56 x +/- 0.59 adducts/10(8) nucleotides [relative adduct level (RAL)]).
      Elevation in the production of mutagenic urine from control and treated animals
      was linked to increases in intestinal nitroreductase and beta-glucuronidase
      activities; however, the only significant alachlor-related effects were an
      increase in small intestinal 1-week beta-glucuronidase and 5-week
      dehydrochlorinase activities. The increased urine mutagenicity and hepatic DNA
      adduct formation indicates that alachlor has a transient effect on DNT
      bioactivation that apparently is unrelated to intestinal bioactivation.

PMID- 9585267
TI  - Mutagenic activation of aromatic amines by molluscs as a biomarker of marine
      pollution.
AB  - Mutagenic activation of arylamines by mollusc S9 fractions was evaluated as a
      biomarker for marine pollution. Two bivalve species were used as bioindicators,
      the common mussel (Mytilus edulis) and the striped venus (Chameleo gallina). A
      strain of Salmonella typhimurium overproducing O-acetyltransferase was used as
      indicator of mutagenicity. Mussels from an area of the North Atlantic Spanish
      zone that was exposed to an accidental crude oil spill were compared to bivalves
      from a reference area. C. gallina samples were from low polluted and highly
      polluted areas of the South Atlantic Spanish littoral. The promutagen 2
      aminoanthracene (2-AA) was activated to mutagenic derivative(s) by S9 fractions
      from both C. gallina and M. edulis. Animals from contaminated sites showed higher
      arylamine activation capabilities than reference animals. This was further
      correlated with the mutagenic activities of corresponding cyclopentone
      dichloromethane animal extracts. 2-AA activation by mollusc S9 was potentiated by
      alpha-naphthoflavone (ANF), known to inhibit PAH-inducible CYP1A cytochromes from
      vertebrates, but inhibited by methimazole (MZ), a substrate of the flavin
      monooxygenase (FMO) system. 2-AA-activating enzymes were mainly cytosolic; this
      localization clearly suggests that such activity could be attributed to soluble
      enzymes, different from the CYP1A or FMO systems. In conclusion, mutagenic
      activation of arylamines by mollusc S9, using as indicator a strain of Salmonella
      typhimurium that overproduces O-acetyltransferase, could be a reliable biomarker
      for marine pollution.

PMID- 9585268
TI  - White-ivory assay of Drosophila melanogaster under deficient repair conditions.
AB  - The prediction ability of a test to detect genotoxic activity may be increased,
      at least from a theoretical point of view, by carrying it out under deficient
      repair conditions. The white-ivory (w[i]) assay of Drosophila melanogaster is a
      somatic mutation and recombination test (SMART) that essentially differs from
      other SMARTs by the endpoints that can be detected. In this article, we study the
      consequences, with the w(i) assay, of the introduction of two mutations, mus201
      and mei-41, which produce deficiency in two different repair mechanisms: the
      nucleotide excision repair system and in a G2/M cell-cycle checkpoint,
      respectively. Ten chemicals, previously classified as positive in the w(i) assay,
      have been assayed in both deficient repair conditions. As in the w/w+ and
      mwh/flr3 SMARTs, the results obtained with the w(i) assay show that the use of
      deficient repair strains does not improve the detection of genotoxic effects.
      However, the utilization of these deficient repair strains has been shown to be a
      useful tool in mechanistic studies. In fact, it seems that the nucleotide
      excision repair system mainly eliminates some spontaneous and chemically-induced
      damages involved in the reversion of w(i), whereas the repair system deficient in
      mei-41 flies is partly necessary to recover revertant w(i) spots.

PMID- 9585269
TI  - The epinephrine test dose in obstetrics: note the limitations.

PMID- 9585270
TI  - Propofol does not ameliorate cerebral venous oxyhemoglobin desaturation during
      hypothermic cardiopulmonary bypass.
AB  - Reductions in cerebral venous oxyhemoglobin saturation (SjO2) occur during the
      rewarming phase of hypothermic cardiopulmonary bypass (CPB). We prospectively
      investigated the effects of propofol on these reductions in SjO2 (SjO2 <50%).
      Fiberoptic jugular bulb catheters were inserted in 30 patients undergoing
      coronary artery bypass grafting. Patients were randomly allocated to a test or
      control group. Test group patients (n = 15) received a propofol IV infusion
      titrated to electroencephalographic burst suppression during CPB. No significant
      differences in SjO2 <50% were found between the groups either by blood sampling
      and bench oximetry or fiberoptic oximetry. The arteriovenous difference in
      lactate concentration became negative in 59 of 120 samples. Propofol was
      associated with an increased incidence of hypotension (mean arterial pressure <50
      mm Hg) (P = 0.023), an increased requirement for vasoconstrictor therapy (P =
      0.025), and increases in the lactate oxygen index (P < 0.01). Propofol, when
      administered in doses that produce electroencephalographic burst suppression,
      does not attenuate the frequency or extent of reductions of SjO2 below 50% during
      rewarming from hypothermic CPB. However, it is associated with arterial
      hypotension and an increase in cerebral anaerobic metabolism. IMPLICATIONS:
      Reductions in cerebral venous oxyhemoglobin saturation during the rewarming phase
      of cardiopulmonary bypass may be related to brain injury. When administered in
      doses sufficient to produce electroencephalographic burst suppression, propofol
      did not attenuate the frequency or extent of such reductions in cerebral venous
      oxyhemoglobin saturation.

PMID- 9585272
TI  - Anesthetic management of a patient undergoing minimally invasive myocardial
      revascularization before lung transplantation.

PMID- 9585271
TI  - Etomidate adversely alters determinants of left ventricular afterload in dogs
      with dilated cardiomyopathy.
AB  - We tested the hypothesis that etomidate produces similar alterations in left
      ventricular (LV) afterload in dogs with normal LV function or dilated
      cardiomyopathy. Dogs were instrumented for LV and aortic pressures, and aortic
      blood flow. LV afterload was measured with aortic input impedance and quantified
      with a three-element Windkessel model. In one group of experiments, dogs (n = 6)
      were paced at 240 bpm for 18 +/- 2 days (mean +/- SEM). Hemodynamic data were
      recorded in sinus rhythm in the conscious state and during etomidate anesthesia
      (5, 10, and 20 mg x kg(-1) x h(-1)). Identical experiments were conducted in a
      separate group of chronically instrumented dogs not subjected to LV pacing (n =
      6). No changes in heart rate and arterial and LV pressures were observed during
      etomidate anesthesia in cardiomyopathic dogs. There were decreases in arterial
      and LV systolic pressure during the administration of 20 mg x kg(-1) x h(-1)
      etomidate to dogs with normal LV function. Etomidate significantly (P < 0.05)
      increased total arterial resistance (R; 3220 +/- 290 dynes x s x cm(-5) during
      control to 6110 +/- 790 dynes x s x cm(-5) during 10 mg x kg(-1) x h(-1)) and
      characteristic aortic impedance (Zc; 141 +/- 22 dynes x s x cm(-5) during control
      to 161 +/- 23 dynes x s x cm(-5) during 20 mg x kg(-1) x h(-1)) and decreased
      total arterial compliance (C; 0.70 +/- 0.15 mL/mm Hg during control to 0.45 +/-
      0.07 mL/mm Hg during 10 mg x kg(-1) x h(-1)) in cardiomyopathic but not healthy
      dogs. Etomidate markedly reduced mean aortic blood flow (2.26 +/- 0.17 L/min
      during control to 1.39 +/- 0.20 L/min during 10 mg x kg(-1) x h(-1)) and
      increased the time constant of LV relaxation (54 +/- 3 ms during control to 74 +/
      9 ms during 20 mg x kg(-1) x h(-1)) in dogs with LV failure. Arterial pressure
      is maintained during etomidate anesthesia in the presence of LV dysfunction as a
      result of increases in R and Zc and decreases in C. These deleterious increases
      in LV afterload further compromise LV systolic and diastolic performance in dogs
      with dilated cardiomyopathy. IMPLICATIONS: The results of this investigation
      indicate arterial pressure is maintained during etomidate anesthesia as a
      consequence of increases in left ventricular (LV) afterload that further diminish
      LV systolic and diastolic performance in the presence of impaired LV function.

PMID- 9585273
TI  - Intrathecal sufentanil analgesia for extracorporeal shock wave lithotripsy in
      three patients with aortic stenosis.

PMID- 9585274
TI  - A comparison of awake versus paralyzed tracheal intubation for infants with
      pyloric stenosis.
AB  - This prospective, nonrandomized, observational study of 76 infants with pyloric
      stenosis was conducted at an academic children's hospital and compared awake
      versus paralyzed tracheal intubation in terms of successful first attempt rate,
      intubation time, heart rate (HR) and arterial hemoglobin oxygen saturation (SpO2)
      changes, and complications. Three groups were determined by intubation method:
      awake (A) with an oxygen-insufflating laryngoscope, after rapid-sequence
      induction (R), or after modified rapid-sequence induction (M) including
      ventilation through cricoid pressure. Successful first attempt intubation rate
      was 64% for Group A versus 87% for paralyzed Groups R and M (P = 0.028). Median
      intubation time was 63 s in Group A versus 34 s in Groups R and M (P = 0.004).
      Transient, mild decreases in mean HR and SpO2 and incidences of significant
      bradycardia and decreased SpO2 did not vary by group. Complications, including
      bronchial or esophageal intubation, emesis, and oropharyngeal trauma, were few.
      Senior anesthesiologists intervened in four tracheal intubations. We advocate
      anesthetized, paralyzed tracheal intubation because struggling with conscious
      infants takes longer, often requires multiple attempts, and prevents neither
      bradycardia nor decreased SpO2. After induction, additional mask ventilation with
      O2 confers no advantage over immediate tracheal intubation in preserving SpO2.
      IMPLICATIONS: In our children's hospital, awake tracheal intubation was not
      superior to anesthetized, paralyzed intubation in maintaining adequate
      oxygenation and heart rate or in reducing complications, and should be abandoned
      in favor of the latter technique for routine anesthetic management of otherwise
      healthy infants with pyloric stenosis.

PMID- 9585275
TI  - Simulation of an epidural test dose with intravenous epinephrine in sevoflurane
      anesthetized children.
AB  - An epidural test dose containing small doses of epinephrine does not produce a
      reliable increase in heart rate (HR) in children under halothane anesthesia.
      Because sevoflurane is increasingly used in clinical practice, we designed the
      present study to determine the hemodynamic responses to, and efficacy of, a
      simulated IV test dose containing a small dose of epinephrine in sevoflurane
      anesthetized children. Sixty ASA physical status I infants and children (4.1 +/-
      2.5 yr) undergoing elective minor surgeries were studied during 1.0 minimum
      alveolar anesthetic concentration of sevoflurane and 60% nitrous oxide in oxygen.
      The patients were randomly assigned to receive either saline (n = 15), a test
      dose consisting of 1% lidocaine (0.1 mL/kg) with 1:200,000 epinephrine (0.5
      microg/kg, n = 15), atropine 0.01 mg/kg followed 5 min later by saline (n = 15),
      or atropine followed by the test dose (n = 15) via a peripheral vein to simulate
      intravascular injection of the epidural test dose. HR and systolic blood pressure
      were recorded every 15 and 30 s, respectively. The test dose increased the HR
      from 15 to 60 s and from 15 to 90 s without and with atropine, respectively. Mean
      maximum increases in HR were similar with and without atropine (21 +/- 8 and 22
      +/- 6 bpm, respectively). Of 15 children, 7 and 5 developed HR changes < 20 bpm
      after the test dose with and without atropine, respectively, whereas all children
      who received saline had an increase in HR < 20 bpm. No dysrhythmia occurred
      during the study. Our results indicate that an epidural test dose containing
      epinephrine is unreliable based on the conventional HR criterion (positive if >
      or = 20 bpm increase), but reliable on the modified HR criterion (positive if >
      or = 10 bpm increase) in children anesthetized with sevoflurane. I.v. atropine
      before the test dose injection did not improve the efficacy based on the
      conventional HR criterion. Because test doses of epinephrine-containing solution
      are used to determine whether an epidural catheter is intravascular, it is
      important to define the optimal test dose under sevoflurane anesthesia.
      IMPLICATIONS: We found that during sevoflurane anesthesia in children, a heart
      rate increase > or = 10 bpm and a systolic blood pressure increase > or = 15 mm
      Hg, when preceded by atropine, may be reliable indicators for detecting
      intravascular injection.

PMID- 9585276
TI  - Clearance of morphine in postoperative infants during intravenous infusion: the
      influence of age and surgery.
AB  - We analyzed morphine clearance values in infants receiving the drug by continuous
      i.v. infusion for analgesia after surgery, because we found lower steady-state
      morphine concentrations than we expected from our previous studies. Infants
      received morphine after a loading dose of 0.05 mg/kg and continuous infusion
      calculated to reach a steady-state concentration of 20 ng/mL. Blood was sampled
      twice on Postoperative Day 1 at times separated by at least 2 h, and morphine and
      morphine-6-glucuronide (M-6-G) concentrations were determined by high-performance
      liquid chromatography. Clearance of morphine was calculated as infusion rate
      divided by the steady-state morphine concentration. Morphine given to 26 infants
      by continuous i.v. infusion after major noncardiac surgery has rapidly increasing
      clearance values, from a median value of 9.2 mL x min(-1) x kg(-1) in infants 1-7
      days old, 25.3 in infants 31-90 days old, and 31.0 in infants 91-180 days old to
      48.9 in infants 180-380 days old. Adult clearance values are reached by 1 mo of
      age, more quickly than in infants of the same age previously studied who received
      morphine after cardiac surgeries. M-6-G was measured in all infants. The ratio of
      M-6-G to morphine concentrations was 1.9-2.1 in these infants, which is lower
      than ratios reported in older infants or adults by others, but higher than those
      reported in newborns. Infants with normal cardiovascular systems undergoing
      surgery clear morphine more efficiently than infants of the same age undergoing
      cardiac surgery. IMPLICATIONS: Morphine removal from the body is slow in newborns
      but increases to reach adult values in the first months of life. Calculating the
      clearance of morphine from blood samples drawn during continuous i.v. infusions
      after surgery shows that this maturation occurs more quickly in infants
      undergoing noncardiac surgery (by 1-3 mo of age) than in those receiving morphine
      after cardiac surgery (by 6-12 mo of age).

PMID- 9585277
TI  - Magnetic resonance imaging of the airway in an infant with micrognathia.

PMID- 9585278
TI  - Patient-controlled versus anesthesiologist-controlled conscious sedation with
      propofol for dental treatment in anxious patients.
AB  - In a randomized, cross-over study, we prospectively compared the efficacy and
      quality of two methods to achieve conscious sedation with propofol in 11
      unpremedicated, anxious dental patients. Each patient underwent two dental
      procedures, one that was conducted under target-controlled infusion (TCI) by the
      anesthesiologist (ACS), and the other that used patient-controlled sedation
      (PCS). The initial target concentration in the ACS mode was 2.5 microg/mL, which
      was manipulated in both directions until the desired clinical end point was
      achieved. In the PCS mode, a 4-mg bolus of propofol (10 mg/mL) was delivered at
      each activation of the machine, infused over 7 s without a lockout interval. The
      anxious dental patients could induce and maintain conscious sedation with the PCS
      settings. The mean (range) venous blood propofol concentrations were not
      significantly different with either mode: ACS 1.8 (0.8-2.7) microg/mL and PCS 1.2
      (0.2-2.5) microg/mL. The level of patient satisfaction, quality of sedation, and
      treatability were not different for either mode of sedation. The intensity of
      amnesia for intraoperative events was related to the blood concentrations
      achieved. In the ACS mode, one patient became unresponsive (sedation level 4)
      immediately after the start of sedation. No adverse cardiorespiratory effects
      resulted from either mode of propofol sedation. Five patients expressed a strong
      preference for PCS, and three would prefer ACS in the future. The results of the
      present study suggest that with these PCS settings, a satisfactory level of
      conscious sedation and a high level of patient satisfaction was achieved.
      IMPLICATIONS: In a randomized, cross-over study, the blood propofol
      concentrations necessary to achieve conscious sedation in anxious dental patients
      using a target-controlled infusion conducted by the anesthesiologist versus
      patient-controlled sedation were not different. With the patient-controlled
      sedation settings, a satisfactory level of conscious sedation and a high level of
      patient satisfaction were achieved.

PMID- 9585279
TI  - The effect of epinephrine on small-dose hyperbaric bupivacaine spinal anesthesia:
      clinical implications for ambulatory surgery.
AB  - The effect of adding epinephrine to small doses of spinal bupivacaine on the
      duration of sensory motor block has not been carefully investigated. Twelve
      volunteers underwent hyperbaric bupivacaine spinal anesthesia (7.5 mg) with and
      without epinephrine (0.2 mg) in a randomized, double-blind, cross-over fashion.
      Sensory block was assessed with pinprick, transcutaneous electrical stimulation
      (TES) equivalent to surgical stimulation (at umbilicus, pubis, knee, and ankle),
      and tolerance of a pneumatic thigh tourniquet. Motor block was assessed with
      isometric force dynamometry. Discharge criteria were defined as return of
      pinprick sensation to dermatome S2, ability to ambulate, and ability to urinate.
      Extent of sensory block to pinprick over time was unaffected by the addition of
      epinephrine. However, epinephrine prolonged tolerance of TES at the pubis, knee,
      and ankle (33-48 min, P < 0.05) and of thigh tourniquet (30 min, P < 0.01). Motor
      block was prolonged by epinephrine at the quadriceps and gastrocnemius muscles
      (by 23 and 51 min, respectively, P < 0.002). Achievement of discharge criteria
      was prolonged by 48 min by the addition of epinephrine (P < 0.01). Thus,
      epinephrine may prolong surgical anesthesia for lower abdominal and lower
      extremity surgery and delay time until patients achieve discharge criteria.
      IMPLICATIONS: Using a cross-over study design, 12 volunteers underwent
      bupivacaine spinal anesthesia with and without epinephrine. This study suggests
      that adding epinephrine to bupivacaine may prolong surgical anesthesia and also
      delay patients' discharge.

PMID- 9585280
TI  - The effect of a perioperative clinical pathway for knee replacement surgery on
      hospital costs.
AB  - Clinical pathways are being introduced by hospitals to reduce costs and control
      unnecessary variation in care. We studied 766 inpatients to measure the impact of
      a perioperative clinical pathway for patients undergoing knee replacement surgery
      on hospital costs. One hundred twenty patients underwent knee replacement surgery
      before the development of a perioperative clinical pathway, and 63 patients
      underwent knee replacement surgery after pathway implementation. As control
      groups, we contemporaneously studied 332 patients undergoing radical
      prostatectomy (no clinical pathway in place for these patients) and 251 patients
      undergoing hip replacement surgery without a clinical pathway (no clinical
      pathway and same surgeons as patients having knee replacement surgery). Total
      hospitalization costs (not charges), excluding professional fees, were computed
      for all patients. Mean (+/-SD) hospital costs for knee replacement surgery
      decreased from $21,709 +/- $5985 to $17,618 +/- $3152 after implementation of the
      clinical pathway. The percent decrease in hospitalization costs was 1.56-fold
      greater (95% confidence interval 1.02-2.28) in the knee replacement patients than
      in the radical prostatectomy patients and 2.02-fold greater (95% confidence
      interval 1.13-5.22) than in the hip replacement patients. If patient outcomes
      (e.g., patient satisfaction) remain constant with clinical pathways, clinical
      pathways may be a useful tool for incremental improvements in the cost of
      perioperative care. IMPLICATIONS: Doctors and nurses can proactively organize and
      record the elements of hospital care results in a clinical pathway, also known as
      "care pathways" or "critical pathways." We found that implementing a clinical
      pathway for patients undergoing knee replacement surgery reduced the
      hospitalization costs of this surgery.

PMID- 9585281
TI  - Tests to evaluate intravenous placement of epidural catheters in laboring women:
      a prospective clinical study.
AB  - We prospectively evaluated the diagnostic accuracy of an epinephrine-containing
      epidural test dose (EpiTD) as a marker of intravascular injection in 209
      unmedicated laboring women. Maternal heart rate (MHR) was continuously monitored
      and recorded on a strip chart. A tocodynamometer monitored uterine activity. A
      lumbar epidural catheter was placed and aspirated. If aspiration was positive for
      blood or cerebrospinal fluid (CSF), the catheter was replaced. In uterine
      diastole and with stable MHR, 198 patients received an EpiTD (epinephrine 15
      microg plus lidocaine 45 mg) via the catheter. MHR and the generated HR strip
      were observed. A positive EpiTD was defined as a sudden increase in MHR of 10 bpm
      more than the resting MHR, within one minute after the injection, with a fast
      acceleratory phase of more than 1 bpm. Absence of a tachycardiac response
      suggested a negative EpiTD. If the tachycardiac response was deemed equivocal or
      a uterine contraction followed the EpiTD injection within 1 min, the EpiTD was
      invalidated and repeated. Catheter aspiration was repeated, and the catheter was
      removed if aspiration was positive. All patients with negative EpiTD and
      aspiration received 6-12 mL of epidural bupivacaine 0.25% with or without
      fentanyl 50 microg. Absence of analgesia without signs or symptoms of systemic
      toxicity after a maximum of bupivacaine 30 mg defined failed epidural analgesia.
      All patients with positive EpiTD and negative aspiration received 5 mL of
      lidocaine 2% epidurally as a second test dose (Lido100TD). The presence of
      tinnitus and/or metallic taste defined a positive Lido100TD. There were 176 true
      negatives, 0 false negatives, 14 true positives, and 8 false positives. The
      sensitivity of EpiTD was 100%, the specificity 96%, the negative predictive value
      100%, and the positive predictive value 63%. The prevalence of negative tests was
      88%, and the prevalence of positive tests was 12%. The overall accuracy of an
      EpiTD was 95.5%. We conclude that EpiTD is a reliable test to identify i.v.
      catheters during the performance of lumbar epidural analgesia in laboring
      patients. IMPLICATIONS: Catheters inserted for epidural analgesia in laboring
      patients may accidentally enter a blood vessel. Local anesthetics injected
      through these catheters may cause seizures and cardiac arrest. In this study, we
      concluded that injecting a small amount of epinephrine before injecting a local
      anesthetic frequently helps to identify these misplaced catheters. Few catheters
      may actually be in the correct place even after responses to epinephrine.

PMID- 9585282
TI  - Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for
      cesarean section.
AB  - In a double-blind, randomized trial, 98 parturients undergoing cesarean section
      received either hyperbaric or plain bupivacaine 6.6 mg combined with sufentanil
      3.3 microg as part of a combined spinal-epidural procedure. To prevent
      hypotension, 1000 mL of lactated Ringer's solution, 500 mL of hydroxyethyl starch
      6%, and ephedrine 5 mg were administered i.v. The height of the block was equal
      in both groups, but more patients in the plain group had blocks that were either
      too high or too low (P < 0.01). The number of patients requiring epidural
      supplementation was equal in both groups. Strict criteria were used to treat
      hypotension. The overall incidence of systolic blood pressure (<90 mm Hg) was
      13%, whereas it was more pronounced in the plain group (21% vs 6% in the
      hyperbaric group, P < 0.05), which required more ephedrine (P < 0.05) and in
      which a greater incidence of nausea was noticed (P < 0.05). We conclude that the
      use of a small dose of intrathecal bupivacaine combined with sufentanil plus our
      described preloading regimen resulted in a lower incidence of hypotension.
      Further, we conclude that the use of hyperbaric bupivacaine in this manner
      provides a more reliable block and a lower incidence of hypotension than plain
      bupivacaine. IMPLICATIONS: A small dose of hyperbaric bupivacaine 0.5% combined
      with sufentanil used intrathecally during cesarean section offered a more
      reliable cephalad spread of the spinal block than the glucose-free combination,
      which was reflected in a lower incidence of hypotension and nausea.

PMID- 9585283
TI  - Sterility of anesthetic and resuscitative drug syringes used in the obstetric
      operating room.
AB  - Because of the constant threat of emergent cesarean delivery, anesthetic
      induction and resuscitation drugs are often drawn into syringes and stored in the
      obstetric operating room (OR). This study investigated the potential for
      bacterial and fungal contamination of six drugs (thiopental, succinylcholine,
      ephedrine, atropine, lidocaine, and oxytocin) often prepared in the obstetric OR.
      A total of 756 drug syringes were prepared and stored in the obstetric OR for 8
      days using normal clinical practices. Starting on Day 0, and subsequently on Days
      4 and 8 of the experiment, 42 syringes of each drug were randomly selected from
      the pool, filtered through a 0.45-microm porosity sterile cellulose filter, and
      cultured on 5% sheep blood agar. Of the 756 syringes tested, none grew organisms
      of any type, which indicates a probability of drug sterility of > or = 0.9961
      (95% confidence interval [CI]). The data from the cultures performed on syringes
      on Day 0 indicate a probability of initial contamination of < or = 0.018 (95%
      CI). This study demonstrates a high probability of sterility in drugs drawn into
      sterile syringes and stored at room temperature in an OR environment for up to 8
      days. IMPLICATIONS: Drug syringes stored in emergency operating rooms are
      discarded after 24 h because of possible contamination. We searched for
      microorganisms in drug syringes stored in the operating room for up to 8 days. No
      microbes were detected using standard sterility testing techniques. Adopting
      longer storage periods could result in significant cost savings.

PMID- 9585284
TI  - Anesthetic management of complete tracheal disruption using percutaneous
      cardiopulmonary support system.

PMID- 9585285
TI  - Clonidine premedication decreases hemodynamic responses to pin head-holder
      application during craniotomy.
AB  - The aim of this study was to compare hemodynamic responses to intubation and pin
      head-holder application in two groups of neurosurgical patients given oral
      clonidine (3 microg/kg) or oral temazepam (10-20 mg) 90 min before the induction
      of anesthesia. Fifty patients undergoing elective craniotomy were randomized to
      either group. Anesthesia was induced with i.v. propofol 1500 mg/h, fentanyl 4
      microg/kg, vecuronium 0.15 mg/kg, and lidocaine 1.5 mg/kg and was maintained with
      propofol 6 mg x kg(-1) x h(-1). Mean arterial blood pressure (MAP) and heart rate
      were recorded before the induction of anesthesia and before and after intubation
      and application of the pin head holder. Interventions required to maintain
      hemodynamic stability were compared between groups. Preinduction sedation scores
      and MAP values were similar between groups. MAP was significantly lower (P =
      0.031) in the clonidine group after pin head-holder application. Interventions to
      stabilize MAP were not significantly different between groups (P = 0.11). We
      conclude that clonidine is effective in reducing the MAP increase with pin head
      holder application in patients undergoing craniotomy. IMPLICATIONS: In this
      study, we investigated an approach to the prevention of increased blood pressure
      often seen during the early part of anesthesia for brain surgery. Oral clonidine
      was effective in reducing the mean arterial blood pressure increase resulting
      from pin head-holder application. Clonidine, a blood pressure-reducing drug, was
      given to 25 patients before anesthesia. Their blood pressure measurements were
      then compared with those of 25 patients not given clonidine.

PMID- 9585286
TI  - Cerebral blood flow velocity in patients with subclinical portal-systemic
      encephalopathy.
AB  - Alterations in cerebral blood flow (CBF) are implicated in the etiology of portal
      systemic encephalopathy. We hypothesized that CO2 reactivity of the cerebral
      circulation may be impaired in subjects with chronic liver disease (CLD) who also
      had subclinical portal-systemic encephalopathy (SPSE). We compared the
      relationship between PETCO2 and cerebral blood flow velocity in 10 patients with
      CLD with those of 10 healthy control subjects. Middle cerebral artery mean blood
      flow velocity (MCAMFV) was measured using transcranial Doppler during rest,
      hyperventilation, and hypoventilation. The degree of SPSE was quantified by using
      psychometric testing. Patients with CLD had poorer psychometric test scores
      compared with control subjects. Patients with CLD had lower PETCO2, MCAMFV, and
      blood pressure values and higher heart rates, differing from control subjects in
      all ventilation states. However, CO2 reactivity, the rate of change in MCAMFV to
      changes in ventilation (expressed as percent change in CBF velocity per mm Hg
      change in PETCO2) was similar for both groups (4.6% +/- 0.6% vs 4.2% +/- 0.5% for
      patients with CLD versus control subjects, P = 0.15). IMPLICATIONS: Psychometric
      test scores in patients with chronic liver disease revealed subclinical
      impairment compared with control subjects. Transcranial Doppler measurements of
      middle cerebral artery blood flow with varying PETCO2 were conducted, but the CO2
      response of patients with liver disease was within the range of control subjects.

PMID- 9585287
TI  - The optimal test dose of epinephrine for epidural injection with lidocaine
      solution in awake patients premedicated with oral clonidine.
AB  - We attempted to determine the optimal test dose of epinephrine for use with
      epidural anesthesia in awake patients premedicated with clonidine. Eighty-eight
      adult patients were randomized into two groups [oral premedication with clonidine
      5 microg/kg (CLON) or no premedication (CONT)]. Before induction of general
      anesthesia, heart rate (HR) and blood pressure (BP) were measured for 3 min after
      the i.v. injection of 3 mL of 1.5% lidocaine containing epinephrine (0, 1.25,
      2.5, 5, 7.5, or 15 microg) in a randomized, double-blind manner. We calculated
      95% confidence intervals for the peak HR and BP increases induced by each dose of
      epinephrine. At 7.5 microg, epinephrine induced a significantly greater increase
      in HR and BP in CLON than in CONT. The 95% confidence interval for the HR change
      induced by 7.5 microg of epinephrine in CLON was nearly the same as the accepted
      standard dose of epinephrine (15 microg) in CONT. We conclude that premedication
      with clonidine enhances HR and BP responses to the i.v. administration of
      epinephrine-containing epidural test solutions. Consequently, 7.5 microg of
      epinephrine may be sufficient to enable detection of accidental injection into a
      blood vessel in awake patients premedicated with clonidine 5 microg/kg.
      IMPLICATIONS: Clonidine, a commonly used preanesthetic medication, alters
      patients' cardiovascular responses to drugs such as epinephrine. Our randomized,
      double-blind study suggests that, in awake patients receiving oral clonidine
      premedication, 7.5 microg of epinephrine (half the usual dose) is adequate as an
      indicator of accidental injection into the epidural vessels during epidural
      anesthesia.

PMID- 9585288
TI  - Premedication with fentanyl and midazolam decreases the reliability of
      intravenous lidocaine test dose.
AB  - This study was performed to determine whether premedication with midazolam and
      fentanyl prevents reliable detection of an i.v. lidocaine test dose. Thirty ASA
      physical status I or II patients received either 3 mL of saline or 1.5 mg of
      midazolam (1.5 mL) plus 75 microg of fentanyl (1.5 mL) i.v. in a randomized,
      double-blind fashion. Five minutes later, lidocaine 1 mg/kg was injected i.v. At
      1.5 min before and every minute after lidocaine administration, each subject was
      questioned regarding the presence of four symptoms of systemic lidocaine
      toxicity. Any new tinnitus, perioral numbness, metallic taste, or light
      headedness within 5 min after lidocaine administration was considered a positive
      response. All 15 patients in the saline group (100% sensitivity) had a positive
      response to i.v. lidocaine, but only 9 of 15 patients in the sedation group had a
      positive response (60% sensitivity; P = 0.017). We conclude that midazolam and
      fentanyl premedication decreases the reliability of subjective detection of i.v.
      lidocaine. IMPLICATIONS: Anesthesiologists often rely on subjective symptoms to
      prevent local anesthetic toxicity while performing regional anesthesia. Sedatives
      are often administered during the administration of regional anesthesia. This
      study demonstrates that typical sedation decreases the reliability of detection
      of local anesthetic toxicity by subjective symptoms.

PMID- 9585289
TI  - The effect of varied doses of epinephrine on duration of lidocaine spinal
      anesthesia in the thoracic and lumbosacral dermatomes.
AB  - The efficacy of epinephrine in prolonging spinal analgesia has recently been
      confirmed in the lumbosacral but not in the thoracic, segments. Most previous
      studies used doses of epinephrine smaller than 0.3 mg. We studied the effects of
      0.2, 0.4, or 0.6 mg of epinephrine added to hyperbaric lidocaine 60 mg in 7.5%
      dextrose solution for spinal anesthesia. Eighty patients were randomly divided
      into four groups: Group A received lidocaine without epinephrine, Group B
      received lidocaine plus 0.2 mL (0.2 mg) of epinephrine 1:1000 solution, Group C
      received lidocaine plus 0.4 mL (0.4 mg) of epinephrine, and Group D received
      lidocaine plus 0.6 mL (0.6 mg) of epinephrine. The maximal cephalad sensory level
      was between T2 and T3 for all groups. The median times for analgesia to regress
      two and four segments were significantly prolonged in Group D, but not in either
      Group B or C, compared with those in Group A. Times for regression to T12 and L3
      were significantly prolonged in Groups B, C, and D compared with Group A. We
      conclude that the dose-dependent relationship of spinal analgesia can be applied
      to epinephrine, and that larger doses prolong lidocaine spinal anesthesia in the
      thoracic as well as the lumbosacral dermatomes. IMPLICATIONS: Prolongation of
      lidocaine spinal analgesia by intrathecal epinephrine is established in the
      lumbosacral, but not in the thoracic, dermatomes. Three doses of epinephrine-
      0.2, 0.4, and 0.6 mg--were compared. A dose-dependent response and significant
      prolongation with the 0.6-mg dose in the thoracic dermatomes were confirmed.

PMID- 9585290
TI  - Transient neurologic syndrome in one thousand forty-five patients after 3%
      lidocaine spinal anesthesia.
AB  - Recent reports have discussed the potential risk of transient radicular
      irritation (TRI) after spinal anesthesia with lidocaine. Because we have not
      encountered such neurologic sequelae with the high incidence reported, we
      prospectively examined the incidence of TRI after spinal anesthesia with
      lidocaine. One thousand forty-five adult patients (aged 47 +/- 15 yr) receiving
      spinal anesthesia with 3% hyperbaric lidocaine (1.0-1.5 mL) for anorectal surgery
      were consecutively studied. After the induction of spinal anesthesia, all
      patients were placed in the prone position for surgery. Patients were evaluated
      for neurologic symptoms in the buttocks, thighs, or lower extremities using a
      checklist to standardize data collection. Although there was no complaint of
      neurologic symptoms on Postoperative Day (POD) 1, four patients (0.4%) reported
      aching, hypesthesia, numbness, or dull pain of both lower extremities and
      buttocks by the morning of POD 3. In three patients, the symptoms resolved
      without any treatment by POD 5, whereas in one patient, numbness of the lower
      extremities lasted until POD 7. We conclude that a combination of lidocaine with
      surgical position or leg manipulation during surgery might be a major
      contributing factor in the development of transient neurologic syndrome.
      IMPLICATIONS: Recent studies have reported the potential risk of transient
      neurologic syndrome after lidocaine spinal anesthesia. The current study reports
      a low incidence of such sequelae in 1045 patients undergoing anorectal surgery
      during the prone position. Other factors, such as surgical position, may be
      important in the development of this syndrome.

PMID- 9585291
TI  - Central and peripheral analgesia mediated by the acetylcholinesterase-inhibitor
      neostigmine in the rat inflamed knee joint model.
AB  - Intrinsic cholinergic inhibitory pathways present a key modulating system in pain
      perception. The use of intrathecal (i.t.) acetylcholinesterase-inhibitors, such
      as neostigmine, result in analgesia in both preclinical and clinical models.
      However, whether i.t. neostigmine suppresses tonic persistent pain or has
      peripheral sites of antinociceptive action has not been determined. Thus, we
      studied central (i.t.) and peripheral (intraarticular; i.a.) neostigmine in a rat
      inflamed knee joint model. Inhibition of thermal and mechanical hyperalgesia was
      assessed over 28 h using a modified Hargreaves box and von Frey hairs,
      respectively. I.t. neostigmine resulted in a dose-dependent thermal analgesia
      (50% of maximal effective dose [ED50] 0-4 h: 6.6 microg, 24-28 h: 9.4 microg) and
      mechanical analgesia (ED50 0-4 h: 3.5 microg, 24-28 h: 4.3 microg). I.t. atropine
      reversed analgesia by i.t. neostigmine. I.a. neostigmine also resulted in an i.a.
      atropine reversible dose-dependent increase of thermal analgesia, although it did
      not exceed 60% of a maximal possible analgesic effect with the largest applied
      dose (ED50 0-4 h: 76.2 microg, 24-28 h: 140.1 microg). Partial suppression of
      mechanical hyperalgesia was observed after i.a. neostigmine. We conclude that
      centrally administered neostigmine modulates thermal and mechanical
      antinociception in this animal model of inflammatory pain. These data suggest a
      peripheral site of muscarinic antinociception. IMPLICATIONS: This animal study
      shows that administration of the acetylcholinesterase-inhibitor neostigmine
      results in enhanced levels of the endogenous neurotransmitter acetylcholine,
      which seems to act as one of a group of analgesia-modulating compounds at central
      and peripheral sites in inflammatory pain.

PMID- 9585292
TI  - The effects of cervical epidural anesthesia with bupivacaine on pulmonary
      function in conscious patients.
AB  - Cervical epidural anesthesia (CEA) can affect diaphragmatic function. We
      investigated the effects of CEA on the diaphragm muscle performance, breathing
      pattern, and respiratory drive of 10 healthy patients undergoing hand surgery
      before and after the administration of 0.25% and 0.375% bupivacaine. The lung
      volumes and flows, respiratory rate (RR), minute ventilation, respiratory cycle
      time, occlusion pressure, maximal inspiratory pressure (MIP), and hand grip
      strength were determined. ETCO2 and SpO2 were continuously monitored. The
      diaphragmatic excursion was evaluated using ultrasonography. Although CEA allowed
      painless hand rehabilitation, both 0.25% and 0.375% bupivacaine impaired
      diaphragmatic excursion, with values decreasing from 5.6 to 4.4 and 3.3 cm (P <
      0.05), respectively, during forced sniff maneuvers. In the 0.25% and 0.375%
      bupivacaine groups, the values of MIP decreased from 74 to 56 and 44 cm H2O,
      forced vital capacity decreased from 3.8 to 3.2 and 2.8 L, and hand grip strength
      decreased from 43.3 to 27.8 and 20.5 kg force, respectively (P < 0.05). The tidal
      volume decreased from 0.8 to 0.6 and 0.5 L in the 0.25% and 0.375% bupivacaine
      groups, respectively, the RR increased from 14 to 18 breaths/min in both groups,
      and the occlusion pressure increased from 1.5 to 2.1 and 2.9 cm H2O in the 0.25%
      and 0.375% bupivacaine groups, respectively (P < 0.05). ETCO2 increased from 35.2
      to 38.1 and 39.3 mm Hg in the 0.25% and 0.375% bupivacaine groups, respectively,
      and SpO2 decreased by 2% +/- 1% in the 0.375% bupivacaine group. CEA affects
      diaphragmatic function and the resulting lung volumes and MIP values. The
      observed alterations in breathing pattern and the significant increase in
      ventilatory drive may be caused by changes in the diaphragmatic muscle tension
      and an augmented CO2 load. In conclusion, we do not recommend this technique for
      routine postoperative hand rehabilitation using the studied bupivacaine
      concentrations. IMPLICATIONS: We studied cervical epidural anesthesia in healthy
      patients undergoing hand surgery. The technique allowed painless rehabilitation
      but affected breathing pattern, diaphragmatic function, and respiratory drive. We
      cannot recommend this technique for routine clinical use.

PMID- 9585293
TI  - Comparison of the three-in-one and fascia iliaca compartment blocks in adults:
      clinical and radiographic analysis.
AB  - The 3-in-1 (Group 1) and fascia iliaca compartment (Group 2) blocks, two single
      injection, anterior approach procedures used to simultaneously block the femoral,
      obturator, and lateral femoral cutaneous (LFC) nerves, were compared in 100
      adults after lower limb surgery. Pain control, sensory and motor blockades, and
      radiographically visualized spread of local anesthetic solution were studied
      prospectively. Both approaches provided efficient pain control using 30 mL of 2%
      lidocaine with 1:200,000 epinephrine and 0.5% bupivacaine and 5 mL of contrast
      media (iopamidol). Complete lumbar plexus blockade was achieved in 18 (38%) Group
      1 and 17 (34%) Group 2 patients (n = 50 patients per group). Sensory block of the
      femoral, obturator, genitofemoral, and LFC nerves was obtained in 90% and 88%,
      52% and 38%, 38% and 34%, and 62% and 90% of the patients in Groups 1 and 2,
      respectively (P < 0.05). Sensory LFC blockade was obtained more rapidly for the
      patients in Group 2 (P < 0.05). Concurrent internal and external spread of the
      local anesthetic solution under the fascia iliaca and between the iliacus and
      psoas muscles was noted in 62 of the 92 block procedures analyzed
      radiographically. Isolated external spreads under the fascia iliaca and over the
      iliacus muscle were noted in 10% and 36% of the patients in Groups 1 and 2,
      respectively (P < 0.05). The local anesthetic solution reached the lumbar plexus
      in only five radiographs. We conclude that the fascia iliaca compartment block is
      more effective than the 3-in-1 block in producing simultaneous blockade of the
      LFC and femoral nerves in adults. After both procedures, blockade was obtained
      primarily by the spread of local anesthetic under the fascia iliaca and only
      rarely by contact with the lumbar plexus. IMPLICATIONS: In adults, the two
      anterior approaches, 3-in-1 and fascia iliaca compartment blocks, provide
      effective postoperative analgesia. The fascia iliaca compartment technique
      provides faster and more consistent simultaneous blockade of the lateral femoral
      cutaneous and femoral nerves. Sensory block is caused by the spread of local
      anesthetic solution under the fascia iliaca and only rarely to the lumbar plexus.

PMID- 9585294
TI  - A comparison of patient-controlled analgesia with lornoxicam versus morphine in
      patients undergoing lumbar disk surgery.
AB  - The analgesic efficacy and tolerability of lornoxicam (Xefo; Nycomed Pharma A/S,
      Roskilde, Denmark), a new nonsteroidal antiinflammatory drug, was compared with
      that of morphine in a double-blind, randomized, parallel-group study of 96
      patients with at least moderate pain after lumbar microsurgical discectomy. Both
      drugs were administered i.v. via a patient-controlled analgesia (PCA) for up to
      24 h postoperatively. Efficacy was assessed by comparing mean hourly pain
      intensity differences, mean hourly pain relief, and total pain relief (TOTPAR)
      values derived from a 5-point verbal rating scores of pain intensity and pain
      relief at several time points over 24 h. Of 79 patients included in a per
      protocol analysis, statistically significant equivalence of lornoxicam and
      morphine was shown by TOTPAR values of 31.6 and 28.9, respectively (P = 0.048).
      Trends toward slightly faster onset of analgesia with morphine and slightly
      greater PCA demands with lornoxicam were observed initially, which may partly
      have been due to a higher baseline pain intensity in the lornoxicam group.
      Lornoxicam caused fewer adverse events than morphine (21.7% vs 38.0% of patients,
      respectively), most of which were mild or moderate in severity. These results
      suggest that lornoxicam is an alternative to morphine when administered by PCA
      for the treatment of moderate to severe postoperative pain. IMPLICATIONS: After
      surgery for lumbar disk disease, patients obtained statistically equivalent pain
      relief with lornoxicam and morphine when administered by patient-controlled
      analgesia. However, lornoxicam was associated with a lower incidence of adverse
      events. This study suggests that lornoxicam provides an alternative to morphine
      for the treatment of postoperative pain.

PMID- 9585295
TI  - Quantifying oral analgesic consumption using a novel method and comparison with
      patient-controlled intravenous analgesic consumption.

PMID- 9585296
TI  - Posterior subcapsular cataract formation associated with multiple lumbar epidural
      corticosteroid injections.

PMID- 9585297
TI  - Lumbar sympathetic ganglion block in a patient with painful legs and moving toes
      syndrome.

PMID- 9585298
TI  - The effect of nitrous oxide on chest wall function in humans and dogs.
AB  - The purpose of this study was to determine the effects of nitrous oxide (N2O) on
      the chest wall of anesthetized humans and dogs. Six human subjects and six
      mongrel dogs were studied during 1 minimum alveolar anesthetic concentration
      halothane anesthesia before and during the substitution of 70% N2O for 70% N2 in
      the inspired gas mixture. On a separate occasion, measurements also were made in
      pentobarbital-anesthetized dogs. Respiratory muscle activity was measured using
      electromyographic (EMG) electrodes. Chest wall configuration was determined by
      using fast three-dimensional computed tomography in dogs and by using respiratory
      impedance plethysmography in humans. N2O consistently decreased inspiratory
      ribcage displacement, a decrease attributable in dogs to decreased inspiratory
      activation of parasternal intercostal muscles; parasternal intercostal activity
      was not present in anesthetized humans. The decrease in ribcage motion decreased
      the tidal volume in humans, but not in dogs, because displacement of the
      diaphragm was better preserved in dogs, in association with changes in diaphragm
      EMG activation. N2O significantly increased phasic expiratory muscle activity in
      halothane-anesthetized humans and pentobarbital-anesthetized dogs. Thus, as has
      been demonstrated for other anesthetics, the actions of N2O are caused by
      alterations in the distribution and timing of neural drive to the respiratory
      muscles, rather than by a global depression of respiratory motoneuron drive.
      IMPLICATIONS: In this study, we examined the effects of nitrous oxide on
      breathing in halothane-anesthetized dogs and humans. Nitrous oxide affected
      breathing by changing the distribution and timing of neural drive to the
      respiratory muscles in a species-dependent manner, rather than by causing a
      global depression of their activity.

PMID- 9585299
TI  - The inhibition by dantrolene of L-arginine transport and nitric oxide synthase in
      rat alveolar macrophages.
AB  - Dantrolene decreases the free cytosolic Ca2+ level via inhibition of calcium
      release from the sacroplasmic reticulum. However, the effect of dantrolene on L
      arginine transport and nitric oxide synthase (NOS) activity is still unknown. In
      this study, we examined the effects of dantrolene on L-arginine transport and
      activity of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide
      (LPS) and interferon gamma (IFN-gamma) in rat alveolar macrophages. Incubation of
      cells with LPS (1 microg/mL) and IFN-gamma (100 u/mL) for 24 h resulted in
      significant increases in nitrite production and L-arginine transport. In the
      presence of dantrolene (100 microM) or inhibitors of NOS, such as aminoguanidine
      (100 microM), N(G)-monomethyl-L-arginine (100 microM), the nitrite production and
      L-arginine transport were significantly inhibited compared with that in the LPS +
      IFN-gamma group. Furthermore, the results of kinetic analysis indicate that the
      suppression of L-arginine transport by dantrolene was caused by selective
      decrease of the velocity of transport (Vmax) without affecting the affinity (Km)
      for L-arginine. In addition, dantrolene also attenuated the activity of iNOS in a
      dose-dependent manner. We conclude that the mechanisms by which dantrolene
      attenuated NO synthesis may be associated with the inhibition of availability of
      L-arginine by reducing the affinity for L-arginine, accompanied by a parallel
      decrease of the activity of iNOS. IMPLICATIONS: In this study, we demonstrated
      that dantrolene, a drug that reduces the intracellular Ca2+ level, can inhibit L
      arginine availability and inducible nitric oxide synthase activity in
      macrophages. Our finding may provide a novel therapeutic approach using
      dantrolene to prevent hypotension associated with an activation of inducible
      nitric oxide synthase in endotoxemia.

PMID- 9585300
TI  - Circuit absorption of halothane, isoflurane, and sevoflurane.
AB  - Uptake of inhaled anesthetics may be measured as the amount of anesthetic infused
      to maintain a constant alveolar concentration of anesthetic. This method assumes
      that the patient absorbs all of the infused anesthetic, and that none is lost to
      circuit components. Using a standard anesthetic circuit with a 3-L rebreathing
      bag simulating the lungs, and simulating metabolism by input of carbon dioxide,
      we tested this assumption for halothane, isoflurane, and sevoflurane. Our results
      suggest that after washin of anesthetic sufficient to eliminate a material
      difference between inspired and end-tidal anesthetic, washin to other parts of
      the circuit (probably the ventilator) and absorbent (soda lime) continued to
      remove anesthetic for up to 15 min. From 30 min to 180 min of anesthetic
      administration, circuit components absorbed trivial amounts of isoflurane (12 +/-
      13 mL vapor at 1.5 minimum alveolar anesthetic concentration, slightly more
      sevoflurane (39 +/- 15 mL), and still more halothane (64 +/- 9 mL). During this
      time, absorbent degraded sevoflurane (321 +/- 31 mL absorbed by circuit
      components and degraded by soda lime). The amount degraded increased with
      increasing input of carbon dioxide (e.g., the 321 +/- 31 mL increased to 508 +/-
      48 mL when carbon dioxide input increased from 250 mL/min to 500 mL/min).
      Measurement of anesthetic uptake as a function of the amount of anesthetic
      infused must account for these findings. IMPLICATIONS: Systems that deliver
      inhaled anesthetics may also remove the anesthetic. Initially, anesthetics may
      diffuse into delivery components and the interstices of material used to absorb
      carbon dioxide. Later, absorbents may degrade some anesthetics (e.g.,
      sevoflurane). Such losses may compromise measurements of anesthetic uptake.

PMID- 9585301
TI  - Halogenated anesthetics inhibit Pseudomonas aeruginosa growth in culture
      conditions reproducing the alveolar environment.
AB  - We assessed the effects of halogenated anesthetics on Pseudomonas aeruginosa
      growth in a liquid nutrient broth. Sterile Petri dishes (3.5-cm diameter) were
      filled with a 1-mL suspension of a Pseudomonas aeruginosa strain and incubated at
      37 degrees C. Exposure of bacterial plates to halothane, isoflurane, and
      enflurane administered at 1 and 2 minimum alveolar anesthetic concentration (MAC)
      were studied for different exposure times (1, 2, 3, and 4 h) using an airtight
      chamber. For each time, a control point was obtained. Serial dilutions and agar
      plates were made, and developed colonies were counted. A significant decrease in
      bacterial growth was observed from the second hour of exposure to every
      halogenated anesthetic. For long periods of exposure (3 and 4 h), bacterial
      growth was significantly reduced in the plates exposed to 2 MAC compared with 1
      MAC. The maximal inhibition was observed after a 4-h exposure at 2 MAC and
      reached 60%, 49%, and 42% for halothane, isoflurane, and enflurane, respectively.
      We conclude that a decrease in Pseudomonas aeruginosa growth is observed after
      exposure to halogenated anesthetics, but whether this inhibition is clinically
      important remains to be demonstrated. IMPLICATIONS: Bacterial pneumonia is a
      major source of morbidity after general anesthesia. We measured the effects of
      volatile anesthetics on the growth of Pseudomonas aeruginosa, one of the
      pathogens most often isolated in hospital-acquired pneumonia. The experiments
      were performed in vitro in culture conditions reproducing those observed in the
      alveolar space. Volatile anesthetics inhibited the growth of these bacteria, but
      the clinical significance of this fact remains to be determined.

PMID- 9585302
TI  - The effect of sevoflurane on spontaneous sympathetic activity, A delta and C
      somatosympathetic reflexes, and associated hemodynamic changes in dogs.
AB  - This study examined the effect of sevoflurane on spontaneous renal sympathetic
      nerve activity (RSNA), A delta- and C-fiber-mediated somatosympathetic reflexes,
      and hemodynamic changes in anesthetized dogs. RSNA, and A delta and C reflexes
      evoked by electrical stimulation of the radial nerve were observed in multifiber
      recordings of efferent activity in renal sympathetic nerves. Sevoflurane was
      administered at 1%, 2%, 3%, and 4% end-tidal concentrations for periods of 20
      min. The mean A delta reflexes decreased by 20%, 39%, and 54% (P < 0.05 to <
      0.01), and the C reflexes decreased by 38%, 62%, and 74% (P < 0.05 to < 0.01) at
      concentrations of 2%, 3%, and 4%, respectively. The relatively greater effect on
      C reflexes was significant (P < 0.05) and comparable with the effect of mu
      opioids. There was no change in mean RSNA, heart rate (HR), and cardiac output
      (CO) up to 3% sevoflurane, but these decreased by 36%, 24%, and 13% (P < 0.05),
      respectively, at 4% sevoflurane. Sevoflurane 1%-4% caused a virtually linear
      reduction in systemic vascular resistance (SVR) from 7% (P < 0.05) to 44% (P <
      0.05), together with a reduction in mean arterial pressure (MAP) that was
      significant for concentrations greater than 2%. The results indicate that
      sevoflurane causes a greater depression of C compared with A delta reflexes, and
      that the reduction in MAP was entirely due to a decrease in SVR up to 3%, whereas
      at 4% sevoflurane, reductions in sympathetic activity, HR, and CO also
      contributed its depressor effect. IMPLICATIONS: The relatively greater depressant
      effect of sevoflurane on C compared with A delta nociceptive somatosympathetic
      reflexes is similar to mu-opioids. The hypotensive effect of sevoflurane was
      significant at 2% concentration, whereas heart rate, cardiac output and
      sympathetic activity were reduced only at concentrations greater than 3%.

PMID- 9585303
TI  - Awareness with recall during general anesthesia: incidence and risk factors.
AB  - We studied the associated factors and incidence of awareness during general
      anesthesia and the nature of subsequent psychiatric disorders. Patients older
      than 12 yr undergoing surgery under general anesthesia in a secondary care
      hospital during 1 yr were included in the study. The doses of anesthetics were
      calculated for the patients with and without awareness. There were 4818
      operations under general anesthesia; 2612 (54%) patients were interviewed. Ten
      (0.4% of those interviewed) patients were found to have undisputed awareness, and
      there were nine (0.3%) patients with possible awareness. The doses of isoflurane
      (P < 0.01) and propofol (P < 0.05) were smaller in patients with awareness. Five
      patients with awareness underwent a psychiatric evaluation. One patient
      experienced sleep disturbances afterward, but the other four patients did not
      have any after effects. In conclusion, awareness is a rare complication of
      general anesthesia associated with small doses of anesthetics. IMPLICATIONS: In
      an interview of 2612 patients after general anesthesia, 10 (0.4%) patients with
      awareness and 9 (0.3%) patients with possible awareness were found. A
      predisposing factor was small doses of the principal anesthetic. In a psychiatric
      interview, a large proportion of the patients with awareness were found to have
      suffered from depression in the past.

PMID- 9585304
TI  - Factors influencing ketorolac-associated perioperative renal dysfunction.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) are useful for the treatment of
      postoperative pain, but there is continuing concern about adverse effects on
      renal function. We studied the renal effects of ketorolac in an animal model
      using Fischer 344 rats undergoing isoflurane anesthesia and laparotomy. Treatment
      groups--control (C), ketorolac (5 mg x kg(-1) x d(-1)) (K), large-dose ketorolac
      (15 mg x kg(-1) x d(-1)) (KH), dehydration-ketorolac (5 mg x kg(-1) x d(-1))
      (DK), gentamicin (20 mg x kg(-1) x d(-1)) (G), and gentamicin (20 mg x kg(-1) x
      d(-1)) with ketorolac (5 mg x kg(-1) x d(-1)) (GK)--each comprised 10 animals.
      Renal function was assessed before laparotomy and after 3 treatment days using
      concurrent paraaminohippurate and iothalamate clearances, respectively, to
      estimate renal plasma flow and glomerular filtration rate, and by measuring serum
      and urine electrolytes, osmolality, urea, and creatinine. A significant increase
      in serum potassium was found in the GK and DK groups. There were no major changes
      in renal function in the C, K, KH, and DK groups. Mild renal dysfunction was
      found in the G group. We found severe and consistent changes in renal function,
      accompanied by severe, widespread histological changes of acute tubular necrosis,
      in the GK group. In this postoperative rat model, the combination of ketorolac
      and gentamicin was deleterious to renal function. IMPLICATIONS: We examined the
      renal effects of the nonsteroidal antiinflammatory drug ketorolac. Renal function
      was measured in rats before and after surgery and 3 days' drug administration;
      the kidneys studied by using microscopy. Only ketorolac plus the antibiotic
      gentamicin produced marked changes in kidney function and structure.

PMID- 9585305
TI  - Ketamine suppresses the production and release of endothelin 1 from cultured
      bovine endothelial cells.
AB  - Endothelins play important roles in the regulation of vascular tone. We examined
      the effect of ketamine on the secretion of endothelin 1 (ET-1) and its precursor,
      "big" ET-1, from bovine carotid artery endothelial cells (BCAECs). After
      confluent BCAEC cultures were incubated for 24 h with various concentrations of
      ketamine, the antigen levels for both ET-1 and big ET-1 in the culture medium
      were determined by using sandwich enzyme-linked immunosorbent assays. The
      precursor protein ET-1 (preproET-1) mRNA levels were assessed by using Northern
      blotting. On incubation in fresh medium, the BCAECs time-dependently produced and
      secreted ET-1 into the culture medium. The exposure of BCAECs to ketamine dose
      dependently decreased the secretion of ET-1 and big ET-1 in both the serum-free
      and serum-containing conditions. Approximately 40% inhibition was attained by
      treatment with 100 microM ketamine for 24 h. The mRNA encoding preproET-1 was
      expressed much more slowly and to a lesser extent in the presence of ketamine.
      These results suggest that ketamine suppresses the production and release of big
      ET-1 and, therefore, the level of mature ET-1 in vascular endothelial cells.
      IMPLICATIONS: Endothelins are important in the regulation of vascular tone. The
      effect of anesthetics on the production of endothelins is unknown. We examined
      the effect of an anesthetic agent, ketamine, on the production and secretion of
      endothelin 1 from cultured vascular endothelial cells and found that ketamine
      suppressed them.

PMID- 9585306
TI  - The effects of age and gender on the optimal premedication dose of intramuscular
      midazolam.
AB  - We conducted a double-blind study on the effects of age and gender on the optimal
      premedication dose of i.m. midazolam. We randomly divided 100 male and 100 female
      patients in each of three age groups: A = 20-39 yr, B = 40-59 yr, and C = 60-79
      yr (total 600 patients) into five groups according to midazolam dosage: 0.04,
      0.06, 0.08, 0.10, and 0.12 mg/kg. Midazolam was injected i.m. with atropine 0.01
      mg/kg 15 min before the induction of anesthesia. Blood pressure (BP), heart rate,
      respiratory rate, oxygen saturation (SpO2), sedation level, tongue root
      depression, eyelash reflex, and anterograde amnesia were monitored. There were no
      significant differences between male and female patients in any variables in any
      age. Decrease of SpO2 and loss of eyelash reflex were seen with midazolam 0.10
      mg/kg in Group A, and with 0.08 mg/kg in Group B. In Group C, decreases in BP and
      SpO2, loss of eyelash reflex, and depression of the tongue root were observed
      with midazolam 0.06 mg/kg. In conclusion, the optimal doses of i.m. midazolam
      administered 15 min before the induction of anesthesia in male or female patients
      were 0.08, 0.06, and 0.04 mg/kg for Groups A, B, and C, respectively.
      IMPLICATIONS: Midazolam is the most widely used preoperative anxiolytic drug. Our
      purpose was to evaluate the optimal dose of i.m. midazolam that would maximize
      the desired effects and minimize the side effects in a common clinical setting.
      Results indicate that age, but not gender, should affect the i.m. midazolam dose
      selected for premedication.

PMID- 9585307
TI  - The influence of the bolus injection rate of propofol on its cardiovascular
      effects and peak blood concentrations in sheep.
AB  - The influence of the bolus injection rate of propofol on its cardiovascular
      effects has not been extensively studied. We therefore examined the influence of
      the injection rate of i.v. bolus doses of propofol on its acute cardiovascular
      effects and peak blood concentrations in seven chronically instrumented sheep.
      Each received i.v. propofol (200 mg) over 2 min (slow injection) and 0.5 min
      (rapid injection) on separate occasions in random order. The rapid injection was
      associated with more profound decreases in mean arterial blood pressure than slow
      injection (35.7% vs 23.7% maximal reductions from baseline, respectively; P =
      0.02). There were no significant differences between the injection rates for peak
      reductions in myocardial contractility, increases in heart rate, or degree of
      respiratory depression. Concurrently, the rapid injections were associated with
      significantly higher arterial (26.9 vs 11.9 mg/L) propofol concentrations in a
      manner consistent with indicator dilution principles. There were no differences
      in the peak coronary sinus concentrations between the injection rates. We
      conclude that the rapid injection of propofol in the context of the induction of
      anesthesia produced significantly higher peak arterial propofol concentrations
      and suggest that it is these higher concentrations that produced relatively
      greater reductions in arterial blood pressure from rapid injections.
      IMPLICATIONS: Propofol is injected into a vein to initiate anesthesia. It can
      cause a rapid decrease in blood pressure, which may be dangerous to the patient.
      We examined the effect of rapid and slow injection rates of propofol in sheep and
      found that rapid injection caused a greater decrease in blood pressure. This was
      because rapid injection caused higher concentrations of propofol in the blood
      immediately after the injection. We believe that if the same processes occur in
      humans, there may be little advantage in injecting propofol rapidly.

PMID- 9585308
TI  - Buccal absorption of etomidate from a solid formulation in dogs.
AB  - Etomidate is typically administered i.v. for the induction of general anesthesia.
      We believe that oral transmucosal absorption may extend etomidate's use to
      premedication and conscious sedation. Our objective was to study the oral mucosal
      absorption kinetics and bioavailability of etomidate in a solid dose form in
      dogs. A solid dose form containing 50 mg of etomidate in sorbitol for buccal
      administration was prepared. Each dog was administered both i.v. etomidate and
      buccal etomidate on separate days. Serum etomidate concentrations after i.v.
      administration were fit to a two-compartment pharmacokinetic model. The rates at
      which etomidate enters the systemic circulation via buccal mucosal absorption
      were calculated from serum concentrations from mucosal and i.v. administrations
      using model-dependent constrained numerical deconvolution. The apparent
      permeability coefficient and bioavailability were also determined. The mean (+/-
      SD) maximal serum etomidate concentration after buccal mucosal absorption from
      the 50-mg dose unit was 239 +/- 79 ng/mL. The time to reach maximal serum
      concentration was 12.5 +/- 1.8 min. Peak absorption rate of etomidate into the
      systemic circulation was 832 +/- 417 microg/min. For all dogs, 90% or more of the
      absorption via buccal mucosa took place during the period in which the drug was
      in contact with the mucosa (15 min). The apparent transbuccal mucosal
      permeability coefficient was 9.1 +/- 4.2 x 10(-4) cm/s, higher than values of any
      other compounds examined. Bioavailability calculated using the area under the
      serum etomidate concentration versus time curve method and the deconvolution
      method was 13.6% +/- 10.7% and 16.6% +/- 7.6%, respectively. In conclusion,
      etomidate is highly permeable through the canine buccal mucosa. IMPLICATIONS:
      Etomidate is highly permeable through the canine buccal mucosa. Both the onset
      and the termination of buccal mucosal absorption of etomidate are rapid, which
      suggests that titratable delivery of etomidate may be possible by buccal
      administration.

PMID- 9585309
TI  - Hydroxyethyl starch antibodies in humans: incidence and clinical relevance.
AB  - Hydroxyethyl starch (HES) is a plasma expander used for perioperative i.v. fluid
      management, as well as for resuscitation from trauma and shock. HES is very well
      tolerated, and the incidence of anaphylactic reactions is lower than with dextran
      or gelatin. Dextran anaphylaxis is caused by circulating dextran-reactive
      antibodies (ABs) of the immunoglobin G (IgG) class found in most adults.
      Histamine release from mast cells induces adverse reactions after gelatin
      infusion. The cause of adverse reactions due to HES is not yet clear. To
      investigate AB formation due to HES, we collected sera of 1004 patients at least
      14 days after starch administration. Using a highly sensitive enzyme-linked
      immunoabsorbent assay technique, we found one patient with a low 1:10 titer of
      HES-reactive ABs (immunoglobin M [IgM] class). Despite repeated HES infusions, no
      clinical reaction could be detected in this patient. On the basis of a binomial
      distribution, a one-tailed confidence interval (99%) was used to calculate the
      percentage of the occurrence of ABs in general with maximum of 33 in 10,000
      persons (IgM) and 23 in 10,000 persons (IgG). We suggest that HES-reactive ABs
      are extremely rare and that they do not necessarily induce anaphylaxis. Other
      mechanisms may be responsible for adverse reactions due to HES. IMPLICATIONS: The
      frequency of antibody formation due to hydroxyethyl starch, a commonly used
      plasma expander, was prospectively investigated in 1004 patients. Only one
      patient showed transient antibody formation, which was not harmful to the
      patient. This low antigenicity could explain the excellent tolerance of
      hydroxyethyl starch compared with other plasma expanders.

PMID- 9585310
TI  - Is oral clonidine effective in modifying the acute hemodynamic response during
      electroconvulsive therapy?
AB  - Clonidine decreases the stress-induced sympathoadrenal responses to painful
      stimuli and improves hemodynamic stability during general anesthesia. Because
      acute hypertensive responses are often observed immediately after
      electroconvulsive therapy (ECT), we designed a prospective, randomized, placebo
      controlled, cross-over study to assess the effects of four different oral doses
      of clonidine (0.05-0.3 mg per os) on the acute hemodynamic response to ECT.
      Anesthesia was induced with methohexital 1 mg/kg followed by succinylcholine, 1.3
      mg/kg i.v. A total of 110 treatments were evaluated in 22 patients. Noninvasive
      mean arterial pressure (MAP) and heart rate (HR) values, duration of motor and
      electroencephalographic (EEG) seizure activity, and recovery times were recorded.
      Clonidine produced a dose-related decrease in MAP before and after ECT. Although
      clonidine 0.2-0.3 mg per os decreased the peak MAP value after ECT, the changes
      in MAP from the prestimulation values were similar in all treatment groups.
      Clonidine produced no significant changes in HR, duration of motor and EEG
      seizure activity, or recovery times after anesthesia. These data suggest that
      clonidine decreases the peak MAP value after ECT by decreasing MAP immediately
      before the ECT stimulus. IMPLICATIONS: Oral clonidine (0.2-0.3 mg) decreases the
      acute hypertensive response after electroconvulsive therapy; however, this
      antihypertensive effect was achieved by decreasing the blood pressure before the
      electrical stimulus.

PMID- 9585311
TI  - The arterial to end-tidal carbon dioxide gradient increases with uncorrected but
      not with temperature-corrected PaCO2 determination during mild to moderate
      hypothermia.
AB  - End-tidal carbon dioxide (PETCO2) monitoring is recommended as a basic standard
      of care and is helpful in adjusting mechanical ventilation. Gas solubility
      changes with temperature, which might affect the PaCO2 and thereby the gradient
      between PaCO2 and PETCO2 (PA-ETCO2) under hypothermic conditions. We investigated
      whether the PA-ETCO2 changes during mild to moderate hypothermia (36 degrees C-32
      degrees C) using PaCO2 measured at 37 degrees C (uncorrected PaCO2) and PaCO2
      corrected to actual body temperature. We preoperatively investigated 19 patients.
      After anesthesia had been induced, controlled ventilation was established to
      maintain normocarbia using constant uncorrected PaCO2 to adjust ventilation
      (alpha-stat acid-base regimen). Body core temperature was reduced without
      surgical intervention to 32 degrees C by surface cooling. Continuous PETCO2 was
      monitored with a mainstream PETCO2 module. The PA-ETCO2 was calculated using the
      uncorrected and corrected PaCO2 values. During body temperature reduction from 36
      degrees C to 32 degrees C, the gradient between PETCO2 and uncorrected PaCO2
      increased 2.5-fold, from 4.1 +/- 3.7 to 10.4 +/- 3.8 mm Hg (P < 0.002). The PA
      ETCO2 remained unchanged when the corrected PaCO2 was used for the calculation.
      We conclude that when the alpha-stat acid-base regimen is used to adjust
      ventilation, the PA-ETCO2 calculated with the uncorrected PaCO2 increases and
      should be added to the differential diagnosis of widened PA-ETCO2. In contrast,
      when the corrected PaCO2 is used for the calculation of the PA-ETCO2, the PA
      ETCO2 remains unaltered during hypothermia. IMPLICATIONS: We investigated the
      impact of induced hypothermia (36 degrees C-32 degrees C) on the gradient between
      PaCO2 and PETCO2 (PA-ETCO2). The PA-ETCO2 increased 2.5-fold when CO2
      determinations were not temperature-corrected. Hypothermia should be added to the
      differential diagnosis of an increased PA-ETCO2 when the alpha-stat acid-base
      regimen is used.

PMID- 9585313
TI  - Is the Combitube a useful emergency airway device for anesthesiologists?

PMID- 9585312
TI  - Tracheal intubation with rocuronium using the "timing principle".
AB  - We compared the endotracheal intubating conditions after rocuronium, using the
      "timing principle," with those after succinylcholine. The timing principle
      entails administration of a single bolus dose of nondepolarizing muscle relaxant,
      followed by an induction drug at the onset of clinical weakness. Forty-five
      patients were randomly assigned to three groups. Patients allocated to Groups 1
      and 2 received rocuronium 0.6 mg/kg. At the onset of clinical weakness (onset of
      ptosis), anesthesia was induced with thiopental 4-6 mg/kg; intubation was
      accomplished after 45 s in Group 1 and after 60 s in Group 2. Patients in Group 3
      received vecuronium (0.01 mg/kg) 3 min before the administration of thiopental
      and succinylcholine 1.5 mg/kg, and their tracheas were intubated 60 s later by a
      blind anesthesiologist. Intubating conditions were assessed according to a
      grading scale and were either good (5 patients in Groups 1 and 2, 4 patients in
      Group 3) or excellent (10 patients in Groups 1 + 2, 11 patients in Group 3) in
      all patients. Patients were interviewed postoperatively, and all were satisfied
      with the induction of anesthesia. We conclude that rocuronium 0.6 mg/kg provides
      good to excellent intubating conditions 45 and 60 s after the induction of
      anesthesia using the timing principle. IMPLICATIONS: We compared the ease with
      which a breathing tube could be placed in patients using three techniques. The
      standard technique (succinylcholine) was compared with two others in which a
      muscle-relaxing drug (rocuronium) was administered just before the anesthetic
      drug (so-called timing principle). No difference among the techniques was
      observed.

PMID- 9585314
TI  - Efficacy of prolonged large-dose dantrolene for severe neuroleptic malignant
      syndrome.

PMID- 9585315
TI  - Effects of epidural epinephrine on the spinal cord accumulation of epidural
      clonidine in rabbits.

PMID- 9585316
TI  - Cardiac output and onset time of different muscle relaxants.

PMID- 9585317
TI  - The trauma airway: whose responsibility?

PMID- 9585318
TI  - Ultrasound and the femoral three-in-one nerve block: weak methodology and
      inappropriate conclusions.

PMID- 9585319
TI  - The effects of midazolam in propofol-induced anesthesia.

PMID- 9585320
TI  - Case-control and cohort studies in anesthesia.

PMID- 9585321
TI  - Sternocleidomastoid muscle as surface landmark for supraclavicular nerve blocks.

PMID- 9585322
TI  - Tourniquet release time and analgesic effects of intraarticular morphine.

PMID- 9585324
TI  - Natural history of median nerve sensory conduction in industry: relationship to
      symptoms and carpal tunnel syndrome in 558 hands over 11 years.
AB  - We evaluated the natural history of median nerve sensory conduction, hand/wrist
      symptoms, and carpal tunnel syndrome (CTS) in an 11-year longitudinal study of
      289 workers from four industries. Twenty hands which had carpal tunnel release
      surgery were excluded, leaving 558 hands for the primary study group. Overall,
      the trend was for mean sensory latencies and prevalence of slowing to increase,
      the prevalence of symptoms to decrease, and the prevalence of CTS to remain
      unchanged. Among individual hands, nerve conduction abnormalities tended to
      persist (82% 11-year persistence), while symptoms fluctuated widely (13% 11-year
      persistence). There was a strong, direct linear correlation between initial
      severity of slowing and subsequent development of CTS; however, most workers who
      developed de novo slowing did not develop symptoms or CTS. We conclude that
      changes in conduction status of the median nerve occur naturally with increasing
      age and do not necessarily lead to symptoms and CTS.

PMID- 9585323
TI  - Clinical spectrum of botulism.
AB  - Botulism is a paralyzing disease caused by the toxin of Clostridium botulinum.
      The toxin produces skeletal muscle paralysis by producing a presynaptic blockade
      to the release of acetylcholine. Recent studies have pinpointed the site of
      action of the several types of botulinum neurotoxin at the nerve terminal. Since
      the discovery of the toxin about 100 years ago, five clinical forms of botulism
      have been described: 1) classic or foodborne botulism; 2) wound botulism; 3)
      infant botulism; 4) hidden botulism; 5) inadvertent botulism. A clinical pattern
      of descending weakness is characteristic of all five forms. Almost all human
      cases of botulism are caused by one of three serotypes (A, B, or E). Classic and
      wound botulism were the only two forms known until the last quarter of this
      century. Wound botulism was rare until the past decade. Now there are increasing
      numbers of cases of wound botulism in injecting drug users. Infant botulism,
      first described in 1976, is now the most frequently reported form. In infant
      botulism spores of Clostridium botulinum are ingested and germinate in the
      intestinal tract. Hidden botulism, the adult variant of infant botulism, occurs
      in adult patients who usually have an abnormality of the intestinal tract that
      allows colonization by Clostridium botulinum. Inadvertent botulism is the most
      recent form to be described. It occurs in patients who have been treated with
      injections of botulinum toxin for dystonic and other movement disorders.
      Laboratory proof of botulism is established with the detection of toxin in the
      patient's serum, stool, or wound. The detection of Clostridium botulinum bacteria
      in the stool or wound should also be considered evidence of clinical botulism.
      Electrophysiologic studies can provide presumptive of botulism in patients with
      the clinical signs of botulism. Electrophysiologic testing can be especially
      helpful when bioassay studies are negative. The most consistent
      electrophysiologic abnormality is a small evoked muscle action potential in
      response to a single supramaximal nerve stimulus in a clinically affected muscle.
      Posttetanic facilitation can be found in some affected muscles. Single-fiber EMG
      studies typically reveal increased jitter and blocking, which become less marked
      following activation. The major treatment for severe botulism is advance medical
      and nursing supportive care with special attention to respiratory status.

PMID- 9585325
TI  - Conduction pathways of motor evoked potentials following transcranial magnetic
      stimulation: a rodent study using a "figure-8" coil.
AB  - We have examined the conduction pathways of motor evoked potentials (MEPs)
      elicited by transcranial magnetic stimulation, and their correlation with
      locomotor function in rats. MEPs were concomitantly recorded from the spinal cord
      (sMEPs) and the limb muscles (mMEPs) before and after various spinal tract
      ablations. Motor function was also examined using an inclined plane test. sMEPs
      were composed of four negative peaks (N1-N4) and mMEPs of high-voltage, biphasic
      waves. Ventral funiculus transection reduced the N1-N3 peaks and abolished mMEPs.
      Contrarily, dorsal funiculus transection including the pyramidal tract did not
      alter these MEPs. Motor performance on an inclined plane was worse after ventral
      funiculus transection than after other transections. These findings indicate
      that, in rats, the N1-N3 peaks of magnetic sMEPs conduct ventral funiculus
      activity, and that magnetic mMEPs mainly reflect extrapyramidal activities and
      are correlated with locomotor function.

PMID- 9585326
TI  - The Hoffmann reflex of human plantar foot muscles.
AB  - Electrical stimulation of the tibial nerve in the popliteal fossa evoked an M
      wave (10.9 ms) and a late reflex response (38.1 ms) in the plantar foot muscles
      of all 10 volunteers. The late response had a somewhat lower electrical threshold
      than the corresponding M wave (8.5 versus 9 mA), and reached a maximum of
      amplitude when the stimulus intensity was increased, but was strongly suppressed
      by further increased intensity. A more distal stimulation of the tibial nerve at
      the ankle shortened the onset latency of the M wave and lengthened that of the
      late response. The reflex was facilitated by activation of synergists and
      inhibited by activation of antagonists. We showed that the late response was
      contaminated neither by volume conducted activity from the soleus muscle, as
      shown by intramuscular recordings from the abductor hallucis muscle, nor by a F
      wave, as shown by double stimulation. In summary, we conclude that this late
      response in human plantar foot muscles corresponded to an H reflex, which may be
      used to assess alterations of distal motoneuronal excitability.

PMID- 9585327
TI  - A magnetic evaluation of peripheral nerve regeneration: I. The discrepancy
      between magnetic and histologic data from the proximal segment.
AB  - Histologic techniques can quantify the number of axons in a nerve, but give no
      information about electrical conductibility. The number of functional myelinated
      neuronal units in a nerve can be quantified based on a magnetic recording
      technique. When studying reconstructed peripheral nerves a significant difference
      between the results found with these two techniques can be observed. A comparison
      was made between the long-term changes in the number of histologically and
      magnetoneurophysiologically measured neuronal units proximal to a nerve
      reconstruction. This study was performed on 6 New Zealand White rabbits, 20 weeks
      after the peroneal nerve had been reconstructed. The contralateral nerves were
      used as a control. Histologic examination demonstrates a statistically
      significant decrease of approximately 5% in the number of myelinated fibers. The
      magnetoneurophysiological results demonstrate a decrease which is estimated to be
      caused by the loss of approximately 50% of the functional myelinated neuronal
      units in the nerve. Therefore we conclude that of the initially available
      myelinated neuronal units, 5% degenerate completely, 45% are vital but lose their
      signal conducting capability, and the remaining 50% are vital and continue to
      conduct signals. Apparently, only this latter group of 50% of the initially
      available functional neuronal units appears to remain available for functional
      recovery.

PMID- 9585329
TI  - Nerve conduction velocities of single thenar motor axons based on the automated
      analysis of F waves in amyotrophic lateral sclerosis.
AB  - The motor unit number estimate (MUNE), motor unit size, and conduction velocity
      (CV) of thenar surface-recorded motor unit action potentials (S-MUAPs) as
      collected by the automated F-wave technique were analyzed in 13 patients with
      amyotrophic lateral sclerosis (ALS) (aged 29-78 years, mean: 61) and 10 age
      matched normal subjects (aged 49-81 years, mean: 64). Totals of 96 and 100 thenar
      S-MUAPs were collected from ALS patients and normal subjects, respectively. There
      were significant differences (P < 0.001) in the mean estimated numbers and sizes
      of motor units between the ALS patients (MUNE: 41.9, S-MUAP size: 699.6
      microV/ms) and normal subjects (MUNE: 151.2, S-MUAP size: 244.1 microV/ms). The
      mean S-MUAP CV was 46.3 m/s (range: 32-59) for ALS patients and 56.5 m/s (range:
      43-69) for normal subjects (P < 0.001). Mean median motor nerve CVs, measured in
      the forearm segment, were not significantly different (P = 0.79) between ALS
      patients (53.4 m/s) and normal subjects (52.9 m/s), however. Thenar motor unit
      CVs are significantly reduced in ALS patients as compared to normal controls, and
      this may be due to proximal motor nerve slowing.

PMID- 9585328
TI  - A magnetic evaluation of peripheral nerve regeneration: II. The signal amplitude
      in the distal segment in relation to functional recovery.
AB  - Motor and sensory function in a healthy nerve is strongly related to the number
      of neuronal units connecting to the distal target organs. In the regenerating
      nerve the amplitudes of magnetically recorded nerve compound action currents
      (NCACs) seem to relate to the number of functional neuronal units with larger
      diameters regenerating across the lesion. The goal of this experiment was to
      compare the signal amplitudes recorded from the distal segment of a reconstructed
      nerve to functional recovery. To this end, the peroneal nerves of 30 rabbits were
      unilaterally transected and reconstructed. After 6, 8, 12, 20, and 36 weeks of
      regeneration time the functional recovery was studied based on the toe-spread
      test, and the nerve regeneration based on the magnetically recorded NCACs. The
      results demonstrate that the signal amplitudes recorded magnetically from the
      reconstructed nerves increase in the first 12 weeks from 0% to 21% of the
      amplitudes recorded from the control nerves and from 21% to 25% in the following
      23 weeks. The functional recovery increases from absent to good between the 8th
      and the 20th week after the reconstruction. A statistically significant relation
      was demonstrated between the signal amplitude and the functional recovery (P <
      0.001). It is concluded that the magnetic recording technique can be used to
      evaluate the quality of a peripheral nerve reconstruction and seems to be able to
      predict, shortly after the reconstruction, the eventual functional recovery.

PMID- 9585330
TI  - Functional significance of upper and lower motor neuron impairment in amyotrophic
      lateral sclerosis.
AB  - The objective of this study was to examine the contribution of lower motor neuron
      (LMN) and upper motor neuron (UMN) dysfunction to weakness and impaired motor
      control in 27 patients with amyotrophic lateral sclerosis (ALS). Isometric
      strength was measured by dorsiflexor maximum voluntary contraction force (MVC).
      LMN function was measured by tetanic force, twitch force, and the amplitude of
      the compound muscle action potential. UMN function was measured by the speed of
      rapid foot taps, the maximum rate of rise of voluntary force, and the central
      activation ratio [CAR = MVC/(MVC + superimposed tetanic force)]. The results
      suggest that (1) LMN loss appears to be the primary cause of progressive weakness
      in ALS; while (2) UMN impairment in ALS leads to slowing of contraction speed and
      rapid movements, and modest decreases in central activation; and (3) during 6
      months of progression, LMN changes were greater than UMN changes.

PMID- 9585332
TI  - Neuromuscular propagation after fatiguing contractions of the paralyzed soleus
      muscle in humans.
AB  - We analyzed the M wave and torque after repetitive activation and recovery of the
      human soleus muscle in individuals with spinal cord injury. Fifteen individuals
      with complete paralysis had the tibial nerve activated for 330 ms every second
      with a 20-Hz train. The M wave and torque were analyzed before fatigue,
      immediately after fatigue, and during recovery. The torque and three M-wave
      measurements (amplitude, duration, median frequency) changed significantly after
      fatigue in the chronic group, but the M-wave area was not changed. The M wave was
      completely recovered after 5 min of rest, even though the torque remained
      depressed during recovery. The M-wave changes appeared to contribute minimally to
      the reduced torque in individuals with chronic paralysis. The disassociation in
      the M-wave-torque relationship during fatigue and recovery suggests, that
      electrical stimulation under electromyography control is not an ideal method to
      optimize torque in paralyzed muscle.

PMID- 9585331
TI  - Homozygous alpha-sarcoglycan mutation in two siblings: one asymptomatic and one
      steroid-responsive mild limb-girdle muscular dystrophy patient.
AB  - We describe a couple of siblings who have a homozygous mutation in the alpha
      sarcoglycan gene and present a striking clinical difference in their phenotype;
      the brother is asymptomatic, and the sister is affected with mild limb-girdle
      muscular dystrophy. Drug therapy with a new steroid (deflazacort) was done over 6
      months in the mild limb-girdle patient, and we observed objective benefit in
      muscle strength and in functional tests. Side effects were minimal.
      Immunohistochemistry for alpha-sarcoglycan showed reduced intensity of reaction
      in the limb-girdle dystrophy patient and was similar to normal in the
      asymptomatic case. A reduced amount of residual alpha-sarcoglycan protein level
      was found in their muscle biopsies. Unknown epigenetic or environmental factors
      may have an important role in determining protein and clinical phenotype
      expression. This is the first report of a patient with homozygous sarcoglycan
      gene mutation without overt muscle weakness in his adulthood. The spectrum of
      clinical phenotypes in sarcoglycanopathies is therefore wider than previously
      thought.

PMID- 9585333
TI  - The devastating combination of Charcot-Marie-Tooth disease and
      facioscapulohumeral muscular dystrophy.
AB  - A patient with both Charcot-Marie-Tooth (type la) disease and facioscapulohumeral
      muscular dystrophy inherited these from her father and mother, respectively.
      Either disease alone does not significantly alter life expectancy, but the
      unusual combination of these two disease processes was devastating and resulted
      in severe generalized weakness and early death.

PMID- 9585334
TI  - Dystrophinopathy in a young boy with Klinefelter's syndrome.
AB  - We report the first case of a child with mild dystrophinopathy associated with
      Klinefelter's syndrome (karyotype 47, XXY). This 3.5-year-old boy was affected by
      some symptoms suggestive of Becker's muscular dystrophy. Dystrophin
      immunostaining and immunoblotting procedures confirmed the diagnosis, but
      polymerase chain reaction-directed gene analysis failed to reveal any
      macrodeletion. Methylation-based assay did not show preferential X-inactivation.
      This confirmed the coexistence of the two active X-chromosomes (one of which was
      of paternal origin), thus accounting for the mild form of dystrophinopathy in
      this child affected by Klinefelter's syndrome.

PMID- 9585335
TI  - Reciprocal inhibition in forearm muscles in patients with essential tremor.
AB  - Reciprocal inhibition of the H-reflex in the forearm flexor muscles was studied
      in 11 patients with essential tremor and in 10 normal controls. Whereas patients
      and controls had a similar first, disynaptic phase of reciprocal inhibition,
      patients had a significantly reduced second phase. Patients with more severe
      functional impairment had more pronounced abnormalities of reciprocal inhibition.
      Abnormalities of reciprocal inhibition may play a role in the pathophysiology of
      essential tremor and probably arise from defective suprasegmental control.

PMID- 9585336
TI  - Role of the masseter reflex in the assessment of subacute sensory neuropathy.
AB  - In 3 patients with a severe pure sensory neuropathy of subacute onset, the
      masseter reflex remained normal despite absent blink reflex responses and absent
      stretch reflexes in the extremities. In 20 patients with primary disorders of
      peripheral nerve axons or myelin, the masseter reflex was abnormal. This study
      suggests that a normal masseter reflex in patients presenting with a pure sensory
      neuropathy favors a polyganglionopathy rather than a primary axonal sensory
      neuropathy, particularly if the blink reflex is abnormal.

PMID- 9585337
TI  - Involvement of the esophagus in the cramp-fasciculation syndrome.
AB  - A 35-year-old male patient presented with symptoms of a cramp-fasciculation
      syndrome, but also reported difficulties swallowing. Esophageal manometry showed
      spontaneous nonperistaltic contractions, pathologically increased amplitudes and
      duration of the contractile complexes, and an asynchronous propagation.
      Electromyographic evidence of fasciculations in the sternocleidomastoid and
      pectoralis muscles was found. Apparently all types of peripheral motor fibers can
      be involved in this heterogeneous syndrome, including cranial motor nerves, the
      vagal nerve, and enteric motor fibers of the gastrointestinal tract.

PMID- 9585338
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy with diffuse and
      massive peripheral nerve hypertrophy: distinctive clinical and magnetic resonance
      imaging features.
AB  - We present 3 patients with chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) with extensive and diffuse hypertrophy of the nerve
      roots and peripheral nerves. They exhibited slowly progressive sensory impairment
      and distally predominant limb weakness and muscular atrophy, and markedly
      enlarged palpable nerve trunks. They responded beneficially to corticosteroid.
      Magnetic resonance imaging demonstrated diffuse and extensive hypertrophy of the
      peripheral nerves in the four limbs and the spinal nerve roots, with gadolinium
      enhancement in the nerve roots but not in the peripheral nerves. These patients
      were considered to have a hypertrophic variant of CIDP.

PMID- 9585339
TI  - Rare mononeuropathies of the upper limb in bodybuilders.
AB  - Clinical and electrophysiological findings of mononeuropathies of thoracodorsal,
      dorsoscapular, terminal branch of suprascapular, and medial pectoral nerves are
      reported in 4 bodybuilders. All athletes used anabolic steroids. After about 1
      year partial improvement of symptoms was evident in 2 cases and complete recovery
      in the other 2. The data are discussed in the light of the few other existing
      reports and possible pathogenetic mechanisms.

PMID- 9585340
TI  - Multifocal motor neuropathy with conduction block misdiagnosed as multiple
      entrapment neuropathies.
AB  - We describe a 58-year-old male with a few years history of multifocal weakness in
      the upper limbs with minimal to absent sensory complaints. He was diagnosed as
      having multiple compressive neuropathies, which required repeated decompressive
      surgeries. Electrodiagnostic studies prior to diagnosis were limited to a few
      nerves, evaluating only distal segments. Because of delay in making the
      diagnosis, his condition progressed, and possibly because of the unnecessary
      surgeries, he developed atrophy in some muscles, which resulted in significant
      motor disability. He was later diagnosed as having multifocal motor neuropathy
      with conduction block and has partially responded to intravenous immunoglobulin
      therapy.

PMID- 9585341
TI  - Oculopharyngeal muscular dystrophy: non-French-Canadian pedigrees.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is a late adult onset, autosomal
      dominant muscular dystrophy characterized by ptosis and dysphagia. The OPMD gene
      has been localized to chromosome 14q11.2-q13 in French-Canadian pedigrees. We
      report 2 non-French-Canadian families with OPMD. Affected ancestors were
      immigrants to the United States from Italy and Normandy. The Norman pedigree does
      not share the French-Canadian haplotype. OPMD appears to be a heterogeneous
      disorder with similar phenotypes, but probably with different gene loci.

PMID- 9585343
TI  - Mononeuropathy multiplex due to infiltration of lymphoma in hematologic
      remission.
AB  - We report a case of progressive mononeuropathy multiplex in a patient with
      lymphoma in hematologic remission. At the time of presentation there was no
      evidence of meningeal or central nervous system metastasis. At autopsy, extensive
      infiltration of tumor cells was found in both femoral nerves. We review the
      literature pertaining to multifocal malignant lymphoid infiltration of peripheral
      nerves, which can occur during hematologic remission or in the absence of any
      evidence of systemic lymphoma.

PMID- 9585342
TI  - Localization of leukemia inhibitory factor and interleukin-6 messenger
      ribonucleic acids in regenerating rat skeletal muscle.
AB  - In the present study, we characterized both temporal and spatial expression
      patterns of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) messenger
      ribonucleic acids (mRNAs) in injured skeletal muscle using in situ hybridization.
      LIF and IL-6 mRNAs were expressed in mononucleated cells and damaged muscle
      cells. Further, signals for LIF mRNA were also detected in Schwann cell-like
      cells of intramuscular nerves. These results suggest that the earliest events
      involved in the repair of injured muscles and nerves may be triggered by these
      cytokines.

PMID- 9585344
TI  - Clozapine-induced myokymia.

PMID- 9585345
TI  - F-wave elicitable minimum nerve conduction velocity.

PMID- 9585346
TI  - Carpal tunnel syndrome: age as an important factor.

PMID- 9585347
TI  - Nucleolar argyrophilic proteins in dystrophin-deficient muscles.

PMID- 9585348
TI  - Welcome news about levodopa, but uncertainty remains.

PMID- 9585349
TI  - Hypothesis: the role of dopaminergic transporters in selective vulnerability of
      cells in Parkinson's disease.

PMID- 9585350
TI  - Chronic levodopa is not toxic for remaining dopamine neurons, but instead
      promotes their recovery, in rats with moderate nigrostriatal lesions.
AB  - Orally administered levodopa remains the most effective symptomatic treatment for
      Parkinson's disease (PD). The introduction of levodopa therapy is often delayed,
      however, because of the fear that it might be toxic for the remaining
      dopaminergic neurons and, thus, accelerate the deterioration of patients.
      However, in vivo evidence of levodopa toxicity is scarce. We have evaluated the
      effects of a 6-month oral levodopa treatment on several dopaminergic markers, in
      rats with moderate or severe 6-hydroxydopamine-induced lesions of mesencephalic
      dopamine neurons and sham-lesioned animals. Counts of tyrosine hydroxylase (TH)
      immunoreactive neurons in the substantia nigra and ventral tegmental area showed
      no significant difference between levodopa-treated and vehicle-treated rats. In
      addition, for rats of the sham-lesioned and severely lesioned groups,
      immunoradiolabeling for TH, the dopamine transporter (DAT), and the vesicular
      monoamine transporter (VMAT2) at the striatal level was not significantly
      different between rats treated with levodopa or vehicle. It was unexpected that
      quantification of immunoautoradiograms showed a partial recovery of all three
      dopaminergic markers (TH, DAT, and VMAT2) in the denervated territories of the
      striatum of moderately lesioned rats receiving levodopa. Furthermore, the density
      of TH-positive fibers observed in moderately lesioned rats was higher in those
      treated chronically with levodopa than in those receiving vehicle. Last, that
      chronic levodopa administration reversed the up-regulation of D2 dopamine
      receptors seen in severely lesioned rats provided evidence that levodopa reached
      a biologically active concentration at the basal ganglia. Our results demonstrate
      that a pharmacologically effective 6-month oral levodopa treatment is not toxic
      for remaining dopamine neurons in a rat model of PD but instead promotes the
      recovery of striatal innervation in rats with partial lesions.

PMID- 9585351
TI  - Fibroblast growth factor-2/brain-derived neurotrophic factor-associated
      maturation of new neurons generated from adult human subependymal cells.
AB  - The adult mammalian forebrain harbors neuronal precursor cells in the
      subependymal zone (SZ). Neuronal progenitors also persist in the adult human SZ
      and have been cultured from epileptic temporal lobe. In the present study, we
      sought to identify these neural progenitors in situ, and to direct their
      expansion and neuronal differentiation in vitro. We prepared explants of adult
      human SZ, obtained from temporal lobe resections of refractory epileptics. The
      resultant cultures were treated with fibroblast growth factor-2 (FGF-2) for a
      week, with concurrent exposure to [3H]thymidine, then switched to media
      containing brain-derived neurotrophic factor (BDNF) for up to 2 months. Sporadic
      neuronal outgrowth, verified antigenically and physiologically, was observed from
      SZ cultures regardless of FGF-2/BDNF treatment; however, only FGF-2/BDNF-treated
      cultures exhibited profuse outgrowth, and these displayed neuronal survival as
      long as 9 weeks in vitro. In addition, cortical cultures derived from two brains
      generated microtubule-associated protein-2+ neurons, which incorporated
      [3H]thymidine and exhibited significant calcium increments to depolarization. In
      histological sections of the subependyma, both uncommitted and restricted
      progenitors, defined respectively by musashi and Hu protein expression, were
      identified. Thus, the adult human subependyma harbors neural progenitors, which
      are able to give rise to neurons whose numbers can be supported for prolonged
      periods in vitro.

PMID- 9585353
TI  - Pathogenesis of cortical myoclonus studied by magnetoencephalography.
AB  - Myoclonus-associated cortical activities were studied by simultaneous recording
      of a magnetoencephalogram and an electroencephalogram in 6 patients with cortical
      myoclonus due to various causes. Cortical activities were averaged, with respect
      to the precise onset of the myoclonic jerk, to evaluate the myoclonus-associated
      cortical magnetic fields. The estimated generator of their earliest peak was
      localized at the contralateral precentral gyrus in all patients. As judged from
      the direction of the electrical current, surface positive activity preceding the
      electromyographic discharge was detected in 3 patients with cortical reflex
      myoclonus and in 1 patient with possible corticobasal degeneration. In contrast,
      in the remaining 2 patients (Lennox-Gastaut syndrome and Alzheimer's disease),
      magnetic fields time-locked to the myoclonic jerk were associated with surface
      negative activity at the precentral cortex. The present study, applying for the
      first time an off-line jerk-locked back-averaging analysis to
      magnetoencephalography, demonstrated the important role of the precentral cortex
      in generating spontaneous myoclonus. It is most likely that the differing
      polarity of the electromagnetic activity reflects the differing activation
      patterns within the cortical laminar structure in the precentral area, underlying
      the generation of various types of myoclonus.

PMID- 9585352
TI  - Striatal spiny neurons and cholinergic interneurons express differential
      ionotropic glutamatergic responses and vulnerability: implications for ischemia
      and Huntington's disease.
AB  - Striatal spiny neurons are selectively vulnerable in Huntington's disease (HD)
      and ischemia, whereas large aspiny (LA) cholinergic interneurons of the striatum
      are spared in these pathological conditions. We have investigated whether a
      different sensitivity to ionotropic glutamatergic agonists might account for this
      differential vulnerability. Intracellular recordings were obtained from
      morphologically identified striatal spiny neurons and LA cholinergic interneurons
      by using a rat brain slice preparation. The two striatal neuronal subtypes had
      strikingly different intrinsic membrane properties. Both subtypes responded to
      cortical stimulation with excitatory postsynaptic potentials: these potentials,
      however, had a different time course and pharmacology in the two classes of
      cells. Interestingly, membrane depolarizations and inward currents produced by
      exogenous glutamate receptor agonists (AMPA, kainate, and NMDA) were remarkably
      larger in spiny neurons than in LA interneurons. Moreover, concentrations of
      agonists producing reversible membrane changes in LA interneurons caused
      irreversible depolarizations in spiny cells. Our data suggest that the different
      physiological responses induced by the activation of ionotropic glutamate
      receptors may account for the cell type-specific vulnerability of striatal
      neurons in ischemia and HD.

PMID- 9585354
TI  - Absence of transcallosal inhibition following focal magnetic stimulation in
      preschool children.
AB  - Focal transcranial magnetic stimulation of the hand-associated motor cortex was
      used to study normal healthy preschool children (n = 7; mean age, 4.6 years) and
      adults (n = 7; mean age, 29.4 years) under the conditions of standardized tonic
      voluntary contraction of small hand muscles. Callosally mediated inhibitory as
      well as corticospinally mediated inhibitory and excitatory motor effects were
      investigated. Although children had no detectable transcallosal inhibition, their
      corticospinally mediated postexcitatory silent period was present (mean, 140.8 +/
      30.2 msec). It was significantly shorter than in adults (mean, 192.5 +/- 32.0
      msec). The motor thresholds of the cortically elicited muscle responses, measured
      as the lowest stimulus intensity, were significantly higher in children (mean, 89
      +/- 5%) than in adults (mean, 46 +/- 6%). The corticomuscular latency of
      transcranially elicited motor responses revealed no difference between children
      and adults. These observations may reflect maturation processes in the motor
      system. Maturation of at least some direct corticospinal fibers occurs early in
      life and is followed by that of intracortical excitatory and inhibitory
      connections. The maturation of functionally competent callosal connections
      appears to occur after the age of 5 years.

PMID- 9585355
TI  - Modification of levodopa responses by deprenyl (selegiline): an
      electrophysiological and behavioral study in the rat relevant to Parkinson's
      disease.
AB  - From using in vitro intracellular recordings from mesencephalic neurons and
      monoamine-depleted rats, we report that the functions of levodopa in the brain
      are greatly enhanced and prolonged by high doses of the monoamine oxidase (MAO)
      inhibitor deprenyl. Dopaminergic neurons were hyperpolarized and inhibited by
      levodopa application. These effects of levodopa were largely potentiated by
      pretreatment with nonselective doses of deprenyl. Furthermore, when locomotor
      activity induced by levodopa was examined on a rodent model of Parkinson's
      disease, pretreatment of the animals with nonselective doses of deprenyl caused
      an enhancement of the antiparkinsonian action of levodopa. The great increase in
      levodopa responses by deprenyl suggests a likely therapeutic use of this dopamine
      precursor with a higher dosage of the MAO inhibitor, to reduce effectively the
      daily levodopa requirements in Parkinson's disease patients.

PMID- 9585356
TI  - In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil
      autoradiography in hippocampal sclerosis.
AB  - By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have
      previously shown that reductions of central benzodiazepine receptors (cBZRs) are
      restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by
      unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on
      resected hippocampal specimens from the same patients demonstrated loss of cBZRs
      that was over and above loss of neurons in the CA1 subregion. Here, we report the
      first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo
      binding using [3H]FMZ autoradiography. We applied a magnetic resonance imaging
      based method for partial volume effect correction to the PET images of [11C]FMZ
      volume of distribution ([11C]FMZ Vd) obtained in 10 patients with refractory mTLE
      due to unilateral, histologically verified HS. Saturation autoradiography was
      performed on the hippocampal specimens obtained from the same patients, allowing
      calculation of receptor availability ([3H]FMZ Bmax). After correction for partial
      volume effect, [11C]FMZ Vd in the body of the epileptogenic hippocampus was
      reduced by a mean of 42.1% compared with normal controls. [3H]FMZ Bmax,
      determined autoradiographically from the same hippocampal tissue, was reduced by
      a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo
      measurements of cBZR binding for the body of the hippocampus were significantly
      correlated in each individual. Our study demonstrates that reduction of available
      cBZR on remaining neurons in HS can be reliably detected in vivo by using
      [11C]FMZ-PET after correction for partial volume effect.

PMID- 9585357
TI  - Neurological and neuroradiological findings in long-term survivors of allogeneic
      bone marrow transplantation.
AB  - The aim of this study was to assess neurological, neuropsychological, and
      neuroradiological findings in long-term survivors of allogeneic bone marrow
      transplantation (BMT) who were recruited from a hematological outpatient clinic.
      In addition, risk factors for the development of late neurological complications
      were identified. In contrast to previous studies on autopsied patients, our study
      design provoked a bias away from increased neurological sequelae, because
      patients with early complications after BMT were excluded. Fifty-nine allogeneic
      patients and 7 autologous BMT patients underwent clinical examination, short
      neuropsychological testing, and cranial magnetic resonance imaging (MRI) 34 +/-
      26 months after BMT. The pathological results of the neurological examination
      (abnormal 64%) and the MRI examination (white matter lesions, 54%; atrophy, 11%)
      were associated with the occurrence of chronic graft-versus-host disease (GvHD)
      evolving from acute GvHD, with corticosteroid therapy and with cyclosporine
      medication. Neuropsychological impairment (cognitive deficits, 37%) was
      associated with long-term cyclosporine medication and age. No influence of pre
      BMT disease, BMT donor status, or the conditioning regimen was found. These
      results suggest that the frequent neurological abnormalities in long-term
      survivors of allogeneic BMT are associated with chronic GvHD and with the
      resulting immunosuppression as major risk factors.

PMID- 9585358
TI  - High penetrance and pronounced variation in expressivity of GCH1 mutations in
      five families with dopa-responsive dystonia.
AB  - We performed a clinical and molecular genetic analysis in members of five
      families with dopa-responsive dystonia. Four mutations were detected in the gene
      GCH1 that codes for GTP cyclohydrolase I. Two of these mutations, a delG309 in
      exon 1 and a C544T transition in exon 5, have not been described before. They
      result in inactivation of the enzyme by truncation. The remaining two mutations,
      both A to G transitions, a(-2)g in intron 1 and a(-2)g in intron 2, cause
      truncation by abnormal splicing. The genotype of family members was correlated to
      their clinical phenotype (obtained before molecular analysis). Clinical symptoms
      observed in the families included generalized and focal dystonia, abnormal gait,
      and subtle signs such as an abnormal writing test. High penetrance (0.8-1.0) was
      observed in four of five families if minor symptoms and signs were considered. A
      given mutation was more likely to cause symptoms in females than in males, thus
      confirming the well-established higher incidence of dopa-responsive dystonia in
      females than in males.

PMID- 9585359
TI  - Association between centromeric deletions of the SMN gene and sporadic adult
      onset lower motor neuron disease.
AB  - The telomeric copy (t) of the survival motor neuron (SMN) gene is homozygously
      deleted in more than 90% of patients with infantile motor neuron disease (MND).
      In the general population, no homozygous SMNt deletion has been found, whereas 5%
      of centromeric SMN (SMNc) deletions can be observed. Although SMNt deletions
      appear causal for infantile and at least some adult-onset spinal muscular atrophy
      (SMA) (type IV), the respective role of SMN deletions remains unclear in adult
      onset MNDs. We studied SMN gene in three different groups of patients with adult
      onset MNDs. In sporadic amyotrophic lateral sclerosis (ALS; n = 177) and familial
      ALS (n = 66), no SMNt deletion had been found, and the frequency of SMNc
      deletions was not increased. Conversely, among the 14 patients with sporadic pure
      lower MND (LMND), we found 2 patients with homozygous SMNt deletions (14%) and 5
      patients with homozygous SMNc deletions (36%). These data suggest that (1) SMNt
      deletions do not account for the major part, if any, of adult-onset LMND cases;
      and (2) SMNc deletions act as a susceptibility factor for LMNDs in adults. The
      clinical and genetic heterogeneity of LMND cases, including SMA type IV, are yet
      to be unexplained. Further studies on large groups of adult-onset LMND patients
      are warranted to refine its nosology.

PMID- 9585360
TI  - Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2
      transcripts in amyotrophic lateral sclerosis.
AB  - Recently, variant mRNA transcripts for the astroglial glutamate transporter EAAT2
      have been detected in brain tissues of 60% of patients with sporadic amyotrophic
      lateral sclerosis (SALS). We have tested the hypothesis that the gene for EAAT2
      may be defective in some ALS cases. In 16 familial ALS (FALS) pedigrees without
      mutations in SOD1, we failed to detect genetic linkage to the EAAT2 locus. We
      next characterized the genomic organization of the EAAT2 gene and used single
      strand conformation polymorphism analysis of genomic DNA to identify one novel
      mutation in a single SALS patient and two novel mutations in 2 affected FALS
      siblings. In the SALS patient, the mutation substitutes serine for an asparagine
      that might be involved in N-linked glycosylation of the EAAT2 protein. In the 2
      affected individuals in the FALS family, we detected both a mutation in the 5'
      end of intron 7 and a silent G --> A transition at codon 234 in exon 5. It
      remains unclear whether this intron 7 mutation is related to the defective mRNA
      splicing. These studies indicate that germline mutations in the EAAT2 gene are
      infrequent and do not explain the presence of variant mRNA transcripts of EAAT2
      in more than one-half of ALS cases.

PMID- 9585362
TI  - Sleep apnea in patients with postpolio syndrome.
AB  - We studied sleep architecture and sleep apnea pattern in patients with postpolio
      syndrome (PPS). Ten patients with clinical signs of PPS underwent
      polysomnographic recording for two consecutive nights. Although sleep efficiency
      and proportions of sleep stages were within the normal range, sleep architecture
      was disrupted owing to sleep apnea. Patients with bulbar involvement had more
      frequent sleep apnea (mean sleep apnea index, 11.09) than patients without (apnea
      index, 5.88). The former also had significantly more central apnea, which
      occurred more commonly during non-rapid-eye-movement (NREM) than rapid-eye
      movement (REM) sleep, than those without bulbar signs. This finding suggests
      reduction in forebrain control of compromised bulbar respiratory centers during
      NREM sleep in PPS.

PMID- 9585361
TI  - Pretreatment with intraventricular aurintricarboxylic acid decreases infarct size
      by inhibiting apoptosis following transient global ischemia in gerbils.
AB  - The goal of this study was to determine whether aurintricarboxylic acid (ATA), an
      endonuclease inhibitor known to inhibit apoptosis, could ameliorate cell damage
      in a gerbil model of transient ischemia. Transient ischemia was induced in
      gerbils by bilateral carotid artery occlusion for a period of 5 minutes. Four
      micrograms of ATA was administered intraventricularly 1 hour before ischemia, and
      the brains were assessed histologically 1 week later to quantitate cell loss in
      the vulnerable CA-1 subsector of the hippocampus. In a separate set of
      experiments, 4 microg of ATA was administered intraventricularly 1 hour before
      ischemia and the brains were assessed for evidence of DNA fragmentation by the
      TUNEL method. There was only a 16% cell loss compared with nonischemic controls
      in animals pretreated with ATA that was significantly less (p < 0.05) than the
      48% cell loss in animals pretreated with saline alone. TUNEL-positive cells were
      first evident at 3 days and were still present at 7 days subsequent to ischemia.
      Maximal staining occurred at 4 days. Pretreatment with ATA virtually eliminated
      TUNEL staining at 4 days. These results support the hypothesis that the delayed
      cell death secondary to transient ischemia is, in part, apoptotic. Furthermore,
      ATA afforded significant neuronal protection and prevented DNA fragmentation.

PMID- 9585363
TI  - The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury.
AB  - The diazoxide derivative IDRA 21 and other positive modulators of (AMPA)-type
      glutamate receptors are considered potential memory-enhancing agents. However,
      AMPA receptor activation contributes to CA1 hippocampal neuron damage from global
      ischemia in rodents, raising the possibility that 7-chloro-3-methyl-3-4-dihydro
      2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21) or drugs with similar actions may
      worsen ischemic neuronal injury. Here we demonstrate that glutamate plus IDRA 21
      kills cultured rat hippocampal neurons by AMPA receptor activation, and, in vivo,
      12 and 24 mg/kg of IDRA 21 given orally increases CA1 neuron loss produced by 10
      minutes of global ischemia. Treating patients with drugs that potentiate AMPA
      receptor activation will have to consider these potential effects, particularly
      when coexistent with conditions in which excessive activation of AMPA receptors
      may occur (eg, stroke, seizures).

PMID- 9585364
TI  - Expression of the early-onset torsion dystonia gene (DYT1) in human brain.
AB  - Early-onset torsion dystonia, an autosomal dominant disease associated with the
      DYT1 locus on 9q34, is the most frequent genetic form of dystonia. Recent work
      has revealed that the causative mutation in most cases is deletion of a glutamate
      residue from the carboxy terminal of torsinA, a 332 amino acid protein encoded by
      the DYT1 gene. To gain insight into how deletion of a single amino acid can
      produce such a profound movement disorder, we have mapped the expression of the
      DYT1 gene in normal human postmortem brain. DYT1 mRNA is highly enriched in the
      dopamine neurons of the substantia nigra pars compacta. Intense expression was
      also found in the cerebellum and hippocampal subfields. The prominent expression
      of the DYT1 gene within the substantia nigra pars compacta, which provides
      dopaminergic innervation to the basal ganglia, implicates a disturbance of
      dopaminergic function in the pathophysiology of early-onset torsion dystonia.

PMID- 9585365
TI  - Neuropathology of preclinical and clinical late-onset Alzheimer's disease.
AB  - We report on the neuropathological examinations of a 74-year-old woman with
      Alzheimer's disease (AD) and of her 47-year-old nondemented daughter. The brain
      of the mother showed fully developed pathological changes of AD. By contrast, the
      brain of the daughter revealed only perineuronal deposition of diffuse amyloid in
      cerebral cortex and striking abnormalities of the endosomal-lysosomal system,
      without neurofibrillary, glial, or microglial changes. These observations suggest
      that amyloid deposition and endosomal-lysosomal changes are early events in late
      onset AD and that they may precede the onset of dementia by several decades.

PMID- 9585366
TI  - Functional evaluation of inhibition of autonomic transmitter release by
      autoantibody from Lambert-Eaton myasthenic syndrome.
AB  - The effects of the anti-voltage-gated Ca2+ channel (VGCC) antibody obtained from
      patients with Lambert-Eaton myasthenic syndrome (LEMS) on autonomic
      neurotransmission were studied in in-vitro experiments. The releases of
      acetylcholine (ACh) and norepinephrine from the autonomic nerves were evaluated
      by changes in the contractile responses of guinea pig taenia caeci and left atria
      to electric field stimulation, respectively. Incubations for 6 hours with LEMS
      serum and IgG, both of which contain anti-VGCC antibody, markedly suppressed the
      parasympathetic response but did not affect the sympathetic response.
      Pharmacological experiments with specific blockers to the VGCC subtypes showed
      that the Q-type VGCC is closely linked to the genesis of the parasympathetic
      response. We suggest that the anti-VGCC antibody from the LEMS patients
      specifically reduces the ACh release from the parasympathetic nerve by binding to
      the Q-type VGCC.

PMID- 9585367
TI  - Dejerine-Sottas neuropathy and PMP22 point mutations: a new base pair
      substitution and a possible "hot spot" on Ser72.
AB  - The occurrence of mutations in peripheral myelin protein 22 is one of the genetic
      mechanisms associated with Dejerine-Sottas neuropathy (DSN). On direct sequencing
      2 of such patients we have found the first mutation in the third transmembrane
      domain associated with this neuropathy and the fourth Ser72Leu. We propose that
      the Ser72 may be a "hot spot" for DSN and that this should be considered for
      molecular analysis.

PMID- 9585369
TI  - HTLV-I-associated facial nerve palsy in Africans and people of African descent.
      Research Group in Tropical Neurology.

PMID- 9585368
TI  - Detection of primary tumor in paraneoplastic cerebellar degeneration by FDG-PET.

PMID- 9585370
TI  - Postinfection sensory neuropathy associated with IgG anti-GD1b antibody.

PMID- 9585371
TI  - Catastrophic deterioration and hippocampal atrophy after childhood status
      epilepticus.

PMID- 9585372
TI  - Clinical determinants in perioperative cardiac evaluation.
AB  - Perioperative cardiac events are the largest cause of morbidity and mortality for
      patients undergoing elective surgery. As a result, numerous recent studies have
      focused on attempts to identify patients at increased risk for perioperative
      events. These have delineated testing modalities capable of identifying high-risk
      patients, and clinical markers which further stratify patients facing elective
      surgery into high-, medium-, and low-risk subgroups. In this article, the authors
      review the evidence supporting the use of clinical markers of risk to evaluate
      patients before elective surgery. The role of preoperative clinical assessment in
      identifying patients most likely to benefit from further testing or intervention,
      (ie, those at significant risk for short- and long-term cardiac events) is
      stressed. Assessment and intervention for risk factors of long-term cardiac
      disease is also stressed, as the preoperative evaluation represents an
      opportunity for improvement in the short- and long-term cardiac risk profile.
      Finally, the algorithm for preoperative cardiovascular evaluation published
      jointly by the ACC/AHA joint taskforce on practice guidelines is reviewed. This
      algorithm is a synthesis of the current literature, into a cost effective and
      efficient approach to patient evaluation.

PMID- 9585374
TI  - Perioperative cardiac evaluation for noncardiac surgery noninvasive cardiac
      testing.
AB  - Prognostic risk stratification to identify perioperative and long-term cardiac
      risk in selected patients undergoing noncardiac surgery is part of good clinical
      practice. Exercise variables associated with significant increased risk include
      poor functional capacity (eg, <4 metabolic equivalents), marked exercise-induced
      ST segment shift or angina at low workloads, and inability to increase or
      actually decrease systolic blood pressure with progressive exercise.
      Approximately 40% of patients tested before peripheral vascular surgery will have
      an abnormal exercise electrocardiogram (ECG). The predictive value for a
      perioperative event, ie, death or myocardial infarction, ranges from 5% to 25%
      for a positive test and 90% to 95% for a negative test. Whereas exercise cardiac
      imaging is the modality of choice in patients with a noninterpretable exercise
      ECG, pharmacological stress imaging should be used in the 30% to 50% of patients
      who require perioperative noninvasive risk stratification and are unable to
      perform an adequate level of exercise to test cardiac reserve. Myocardial
      perfusion variables predictive of increased cardiac events include severity of
      the perfusion defect, number of reversible defects, extent of fixed and
      reversible defects, increased lung uptake of thallium-201, and marked ST segment
      changes associated with angina during the test. The reported sensitivity and
      specificity of dobutamine-induced echocardiographic wall motion abnormalities in
      patients with peripheral vascular disease is similar to myocardial perfusion
      scintigraphy, but the confidence limits are wider due to the smaller sample size
      in these more recent studies. In conclusion, noninvasive cardiac testing should
      be used selectively in patients undergoing noncardiac surgery; the results
      provide useful estimates of short- and long-term risk of cardiac events, and the
      magnitude of abnormal response on noninvasive testing should be used to formulate
      decisions regarding the need for coronary angiography and subsequent
      revascularization.

PMID- 9585373
TI  - The role of myocardial revascularization preceding noncardiac surgery.
AB  - Of about 6.7 million Americans who have coronary artery disease, approximately
      700,000 undergo various noncardiac operations annually in the United States.
      Perioperative cardiac complications remain the leading cause of morbidity and
      mortality not related to the primary operative procedure; the mechanisms of
      perioperative ischemia and infarction are unclear. Currently, clinicians, using a
      combination of clinical and laboratory findings, can estimate the risk of
      noncardiac surgical procedures with a high degree of precision, but much less is
      known about the preferred approach to patient management after noninvasive risk
      stratification. Coronary angiography and revascularization are frequently
      recommended for those determined by functional tests to be at moderate and high
      risk, but the risks of revascularization are often substantially higher among
      these patients. No randomized, controlled trials exist to guide patient
      management. Quantitative decision analysis based on published nonrandomized data
      suggests that coronary angiography with selective myocardial revascularization
      should be performed to reduce the risk of noncardiac surgery only if the risk of
      noncardiac surgery is greater than 5% and the risk of coronary angiography with
      selective revascularization is less than 3%. On the other hand, if independent
      indications exist for myocardial revascularization, it should generally be
      performed before the noncardiac operation.

PMID- 9585375
TI  - The role of the cardiology consultant: putting it all together.
AB  - Consultation represents the act of providing advice regarding diagnosis and/or
      management and may comprise a major component of a cardiologist's practice. A
      frequent cause for cardiac consultation is preoperative risk assessment. With
      steadily decreasing morbidity and mortality related to noncardiac surgery,
      cardiovascular management strategies that are known to improve long-term outcomes
      should guide decision making in the perioperative setting. The preoperative
      cardiac consultation may represent an opportunity to initiate or modify cardiac
      care including primary and secondary preventive measures. A stepwise approach to
      perioperative cardiac risk assessment, as set forth by joint American College of
      Cardiology and American Heart Association guidelines, should be employed. The
      hallmark of successful preoperative cardiology consultation is effective
      communication with referring physicians. A consultant's good clinical judgement
      will only impact a patient's care if recommendations are communicated
      effectively. There is no substitution for direct, verbal contact. Recommendations
      should be kept to less than five when possible, be brief and specific. The
      consultant should provide contingency plans and follow-up. Good consultative
      technique increases compliance with recommendations and facilitates efficient
      patient care.

PMID- 9585376
TI  - Anesthetic management and perioperative surveillance.
AB  - The intraoperative management of the high-risk patient has received a great deal
      of attention and research during the past decade. Based on the available
      evidence, there appears to be no one best anesthetic technique or agent. More
      importantly, the goals of intraoperative management are to avoid myocardial
      ischemia, which include preventing tachycardia, and maintaining normothermia and
      adequate hematocrit. Perioperative monitoring includes transesophageal
      echocardiography, pulmonary artery catheter and ST segment monitoring.
      Perioperative pharmacological treatment with alpha-2 agonists and beta-adrenergic
      blocking agents are associated with a reduced incidence of perioperative
      myocardial ischemia and improved long-term survival, respectively. Future
      research will be required to determine whether prophylactic therapy or early
      treatment of perioperative myocardial ischemia will lead to improved outcome.

PMID- 9585377
TI  - Surgery-specific considerations in the cardiac patient undergoing noncardiac
      surgery.
AB  - Myocardial infarction after noncardiac surgery in patients with coronary artery
      disease results from the interplay of patient-specific, anesthetic-specific, and
      surgery-specific factors. Surgery-specific factors include the stress response to
      injury, both neurohormonal and hemostatic alterations, and clinically-significant
      operative parameters such as urgency, duration, blood loss, body core
      temperature, fluid shifts, and location of surgery. The impact of these factors
      bears out during the entire perioperative period and influences preoperative risk
      assessment, cardiac evaluation and intervention, intraoperative strategy, and
      postoperative management. Overall, the morbidity and mortality of surgery is
      minimal even in high-risk patients, and the contribution of surgery-specific
      factors to operative risk is subtle compared with that of patient specific
      factors such as severity of coronary disease and other comorbid conditions.
      Nonetheless, the optimal surgical management of patients with coronary disease
      requires the collaborative effort of the anesthesiologist, cardiologist, and
      surgeon.

PMID- 9585378
TI  - Management of specific medical conditions in the perioperative period.
AB  - Patients with a variety of medical conditions known to increase cardiovascular
      risk may require noncardiac surgery. After a preoperative assessment of risk,
      specific attention to medical therapy may be indicated in the perioperative
      period. The perioperative period begins before surgery when routine medical
      therapy may be interrupted, and continues through the surgical procedure and
      convalescence. During these times, the surgical patient is exposed to increased
      risks related to the underlying disease process prompting surgery, stresses
      associated with anesthesia, surgical intervention and postoperative discomfort,
      and alterations in usual medical therapy. With careful attention to risks
      specific to an underlying medical condition, patient monitoring and medical
      management in the perioperative period can be modified to prevent or minimize the
      impact of an adverse cardiac event.

PMID- 9585379
TI  - Plasma GH responses to GHRH, arginine, L-dopa, pyridostigmine, sequential
      administrations of GHRH and combined administration of PD and GHRH in Turner's
      syndrome.
AB  - To investigate GH secretory capacities in patients with Turner's syndrome, GHRH,
      arginine, L-dopa and pyridostigmine (PD) were administered singly and GHRH was
      administered sequentially for 3 days. In addition, plasma GH and TSH responses to
      GHRH and TRH after pretreatment with PD were analyzed to investigate whether the
      hypothalamic cholinergic somatostatinergic system functioned normally. The
      maximal GH responses to GHRH, L-dopa and PD were significantly smaller in
      Turner's syndrome (no.=14) than in normal short children (NSC, no.=14). However,
      there was no difference in plasma GH responses to arginine between the two
      groups. In ten patients with Turner's syndrome, the plasma GH response to GHRH
      did not improve even after the sequential 3-day administrations. Although plasma
      GH and TSH responses to GHRH and TRH were significantly enhanced by the
      pretreatment of PD in NSC (no.=12), these responses were not enhanced in Turner's
      syndrome. Plasma GH response to GHRH in Turner's syndrome with normal body fat
      was still significantly lower than in NSC. It is therefore concluded that
      somatotroph sensitivity to GHRH is decreased in Turner's syndrome and that this
      may be due to the primary defects of the somatotrophs rather than to the
      increased body fat. In addition, the network of cholinergic-somatostatinergic
      systems seemed to be impaired in these patients, while the activity of
      hypothalamic somatostatin neurons was thought to be maintained.

PMID- 9585380
TI  - Post-traumatic hormonal disturbances: prolactin as a link between head injury and
      enhanced osteogenesis.
AB  - Traumatic brain injury (TBI) combined with fractures of long bones or large
      joints is often associated with enhanced osteogenesis (early fracture healing
      accompanied by hypertrophic callus formation and/or heterotopic ossifications).
      Humoral factors that cause enhanced osteogenesis in patients with TBI are not yet
      identified. The aim of this study was to reveal if post-traumatic change(s) of
      hormone levels in patients with TBI and bone fractures could be associated with
      the phenomenon of enhanced osteogenesis. The blood values of adrenocorticotropic
      hormone (ACTH), cortisol, growth hormone (GH), parathyroid hormone (PTH) and
      prolactin (PRL) were studied weekly over a period of three months after injury in
      patients with bone fractures only, those with TBI only or combined bone fractures
      and TBI (patients exerting enhanced osteogenesis). Stress-hormones, ACTH and
      cortisol, or the hormones related to the bone growth (GH and PTH) did not show
      any particular post-traumatic changes in the blood of patients with combined
      injury that could be associated with the enhanced osteogenesis. On the other
      hand, patients with combined bone fractures and TBI accompanied by enhanced
      osteogenesis had significantly elevated PRL levels in blood during the 5th week
      of the post-traumatic period. Thus, the maximal PRL values were measured at the
      time when in this group of patients fractures were in consolidation and
      hypertrophic callus or heterotopic ossifications were developing (as verified by
      x-ray imaging). Hence, PRL does not only influence physiology of the bone
      metabolism but also seems to be one of the humoral factors involved in the
      phenomenon of enhanced osteogenesis in patients with TBI.

PMID- 9585381
TI  - Seventeen-year-long follow-up of a family affected by type 2A multiple endocrine
      neoplasia (MEN 2A).
AB  - This paper reports the results of a 17-year-long follow-up covering 17 members of
      a family affected by multiple endocrine neoplasia (MEN) type 2A, first diagnosed
      in 1980. This family is enrolled in our screening program. The thyroid,
      parathyroid and adrenal glands of the family members were investigated using the
      most sophisticated and sensitive techniques which have become available during
      this period, and their DNA was genetically tested for detecting RET mutations.
      Thanks to the combination of these two approaches it was possible to confirm the
      diagnosis in the members concerned from the genetic point of view, and to achieve
      an early diagnosis in the young members of the last generation before the
      clinical onset of the disease. The detection of a RET mutation also prompted a
      prophylactic thyroidectomy in a four year-old boy, in a pre-tumoral stage of the
      disease. Lastly, evidence is provided that genetic analysis of the DNA of the
      chorionic villi can be carried out as a prenatal test during routine
      amniocentesis.

PMID- 9585382
TI  - Insulin induces tyrosine dephosphorylation of a 92 kDA protein in suspended
      monocytes.
AB  - Monocytes bear insulin receptors similar to those expressed in other tissues, but
      insulin action in these cells remains unclear. There is evidence that adhesion,
      by generating a complex array of irreversible transformations, may modify the
      response of cells to other stimuli, such as hormones. The present study aimed to
      characterise the pattern of insulin induced tyrosine phosphorylation of monocytes
      in suspension. Monocytes in suspension were obtained by sequential gradient
      centrifugation and the tyrosine phosphoproteins were analyzed by immunoblot with
      antiphosphotyrosine antibodies. The major result of the study is that in
      suspended monocytes insulin induced a dose and time dependent dephosphorylation
      of a protein with a molecular mass of about 92 kDa without stimulating the
      tyrosine phosphorylation of the Insulin Receptor Substrat-1 (IRS-1). In
      conclusion, we showed that in monocytes in suspension insulin seems to activate a
      tyrosine phosphatase, which, in turn, dephosphorylates a protein with an apparent
      molecular weight of 92 kDa.

PMID- 9585383
TI  - Cytopathological findings from fine-needle aspiration biopsy are accurate
      predictors of thyroid pathology in patients with functioning thyroid nodules.
AB  - The cytopathological findings after fine-needle aspiration biopsy (FNAB) of
      functioning solitary thyroid nodules (FSTN) are not well defined. This is an
      important issue, once this procedure is the first step in nodule evaluation. This
      study evaluated FNAB findings and correlated these findings with histopathology
      in patients subjected to thyroidectomy. Eleven clinically euthyroid female
      patients (age range: 19 to 47 years) with FSTN, satisfactory specimens from FNAB
      and negative antithyroid antibodies were studied. Seven patients had autonomous
      nodules. The cytopathological findings were of follicular pattern suggestive of
      neoplasia in one case where the histopathological examination confirmed a
      follicular adenoma. In all other 6 autonomous cases, the smears were suggestive
      of colloid goiter and they had surgery due to compressive symptoms (n=4) or
      subclinical hyperthyroidism (n=2). The histopathological results confirmed
      colloid goiter in all except one who presented a follicular adenoma. Four
      patients had functioning thyroid nodules that suppressed their 1311 uptake after
      receiving T3. The cytopathological findings were considered malignant in one case
      surgically confirmed to be a papillary carcinoma. In all other 3 non-autonomous
      cases, the smears were suggestive of colloid goiter and they had surgery due to
      compressive symptoms (n=1), aesthetic reasons (n=11) or increase in nodule volume
      (n=1). The histopathological results confirmed colloid goiter. In conclusion,
      FNAB was an accurate predictor of thyroid pathology in FSTN without false
      positive results in the present study.

PMID- 9585384
TI  - Chronic hypervitaminosis D3 determines a decrease in C-cell numbers and
      calcitonin levels in rats.
AB  - Many papers have reported that chronic hypercalcemia induced either by large
      doses of vitamin D or by the administration of calcium or parathormone, produces
      hypertrophy and hyperplasia of C cells. However, more recent studies suggest that
      the effect of elevated calcium or 1.25(OH)2D3 concentration on the production of
      calcitonin may be more complex than previously suspected. To assess the validity
      of such a response an experimental model, where hypercalcemia was induced with
      vitamin D3 overdose, was designed. Male Wistar rats were administered vitamin D3
      chronically (50,000 IU per 100 ml of drinking water with or without CaCl2). Serum
      calcium and calcitonin levels were determined. C cells were stained by
      immunohistochemistry using calcitonin and neuronal specific enolase (NSE)
      antibodies and their percentage was calculated by a morphometric analysis. We
      also investigated the ultrastructural characteristic of the C cells under
      experimental conditions. C cells did not have a proliferative response rather a
      decrease in their number was observed after 1 month of treatment with 25,000 IU
      of vitamin D3 (1.55 vs 2.43% in control animals) and 3 months with vitamin plus
      CaCl2 (2.27% vs 3.62% in control animals). In addition, no significant changes in
      serum calcitonin levels were observed during the experimental period. We conclude
      that rat C cells do not respond with hypertrophic and hyperplastic changes in a
      hypercalcemic state due to an intoxication with vitamin D3.

PMID- 9585385
TI  - Adrenal cystic lesions: report of 12 surgically treated cases and review of the
      literature.
AB  - Adrenal cysts are rare (0,064%-0,18% in autopsy series) and less than 500 cases
      have been reported in the western literature. Incidental diagnosis of adrenal
      cysts, however, is reported with increasing rates. We observed 12 patients with
      adrenal cyst. Each of them had a careful laboratory and instrumental evaluation;
      all the patients were operated. In our series about 67% of the patients were
      symptomatic (6 patients with abdominal pain, 1 with palpable mass, 1 with
      hemorrhagic shock). No biochemical alteration was observed. Conversely we
      observed an unusual subclinically hyperfunctioning cystic adenoma, potentially
      progressive to a clinically recognizable endocrine syndrome. US, CT and MRI had a
      sensitivity of 66,7%, 80% and 100% respectively. Adrenalectomy was performed in
      all patients. The pathological findings were: 1 epithelial cyst (cystic adenoma),
      2 endothelial cysts (vascular cystic ectasia with adenomatous adrenocortical
      hyperplasia and 1 vascular cyst) and 9 pseudocysts. On the basis of these
      results, we conclude that a careful hormonal, morpho-functional and instrumental
      evaluation is indicated in all adrenal cysts, even if the available diagnostic
      procedures, even when combined, cannot always define their nature. Surgical
      excision, when possible by laparoscopic approach, is indicated in presence of
      symptoms, endocrine abnormalities (even when subclinic), complications, suspicion
      of malignancy and/or large size (>5 cm). Adrenal gland must be excised en bloc,
      also because of the possible presence of other adrenal lesions.

PMID- 9585386
TI  - Low IGF-I levels are often uncoupled with elevated GH levels in catabolic
      conditions.
AB  - Increased GH together with decreased IGF-I levels pointing to peripheral GH
      insensitivity in critically ill patients have been reported by some but not by
      other authors. To clarify whether elevated GH levels are coupled with low IGF-I
      levels in all catabolic conditions, basal GH and IGF-I levels were evaluated in
      patients with sepsis (SEP, no.=13; age [mean+/-SE]=59.2+/-1.2 yr), trauma (TRA,
      no.=16; age=42.3+/-3.4 yr), major burn (BUR, no.=26; age=52.8+/-4.2 yr) and post
      surgical patients (SUR, no.=11; age=55.0+/-4.7 yr) 72 hours after ICU admission
      or after cardiac surgery. GH and IGF-I levels were also evaluated in normal
      subjects (NS, no.=75; age=44.0+/-1.5 yr), in adult hypopituitaric patients with
      severe GH deficiency (GHD, no.=54; age=44.8+/-2.3 yr), in patients with liver
      cirrhosis (LC, no.=12; age=50.4+/-2.8 yr) and in patients with anorexia nervosa
      (AN, no.=19; age=18.7+/-0.8 yr). Basal IGF-I and GH levels in GHD were lower than
      in NS (68.6+/-6.4 vs 200.9+/-8.7 microg/l and 0.3+/-0.1 vs 1.4+/-0.2 microg/l;
      p<0.01). On the other hand, AN and LC showed IGF-I levels (70.4+/-9.1 and 52.4+/
      10.5 microg/l) similar to those in GHD while GH levels (10.0+/-2.8 and 7.9+/-2.1
      microg/l) were higher than those in NS (p<0.01). IGF-I levels in SEP (84.5+/-8.8
      microg/l) were similar to those in GHD, AN and LC and lower than those in NS
      (p<0.01). IGF-I levels in BUR (105.2+/-10.9 microg/l) were lower than in NS
      (p<0.01) but higher than those in GHD, AN, LC and SEP (p<0.01). On the other
      hand, in TRA (162.8+/-17.4 microg/l) and SUR (135.0+/-20.7 microg/l) IGF-I levels
      were lower but not significantly different from those in NS and clearly higher
      than those in GHD, AN, LC, SEP and BUR. Basal GH levels in SEP (0.6+/-0.2
      microg/l), TRA (1.8+/-0.5 microg/l), SUR (2.2+/-0.5 microg/l) and BUR (2.2+/-0.5
      microg/l) were similar to those in NS, higher (p<0.05) than those in GHD and
      lower (p<0.01) than those in AN and LC. In conclusion, our data demonstrate that
      low IGF-I levels are not always coupled with elevated GH levels in all catabolic
      conditions. Differently from cirrhotic and anorectic patients, in burned and
      septic patients GH levels are not elevated in spite of very low IGF-I levels
      similar to those in panhypopituitaric GHD patients. These findings suggest that
      in some catabolic conditions peripheral GH insensitivity and somatotrope
      insufficiency could be concomitantly present.

PMID- 9585387
TI  - Reversible endocrine dysfunction and pituitary stalk enlargement.
AB  - We report 4 patients (3 of which were children) with diabetes insipidus and
      different degrees of hypopituitarism in whom a pituitary stalk enlargement was
      disclosed on imaging techniques, and in whom radiological and functional recovery
      was observed during follow-up. Pituitary substitution therapy with desmopressin,
      thyroxine, hydrocortisone, growth hormone and/or oral contraceptives was
      prescribed. During follow-up, regression of the stalk lesion was seen which was
      spontaneous in 2 cases, following a short course of corticosteroids in another
      and an empirical trial of tuberculostatic drugs in the fourth. A partial recovery
      of pituitary function was also observed. These cases illustrate that pituitary
      stalk enlargement and associated hypopituitarism may be reversible; however, this
      morphological and functional recovery has rarely been described in adults and has
      not been previously reported in children.

PMID- 9585388
TI  - Postmenopausal virilization in a woman with gonadotropin dependent ovarian
      hyperthecosis.
AB  - We report a case of a 66-yr-old woman with progressive hair balding, hirsutism
      and virilization. Gonadotropins and estradiol levels were in the postmenopausal
      range; total testosterone (TT), free testosterone (FT) and 17-hydroxyprogesterone
      (17-OHP) were elevated with dehydroepiandrosterone sulphate, androstendione and
      cortisol serum levels in the normal range, as 24-hr free urinary cortisol. TT, FT
      and 17-OHP were normalized, and FSH and LH fell to premenopausal levels on 18th
      day after a single i.m. injection of the GnRH analogue (GnRHa), triptorelin.
      Then, a diagnosis of hyperandrogenism of ovarian origin was made and bilateral
      ovariectomy was performed. Histological study of gonadal tissue revealed diffuse
      stromal hyperplasia of both ovaries with occasional nests of luteinized cells.
      With immunoperoxidase techniques these cells stained positively for testosterone
      and progesterone. One month after surgery, androgen levels were normalized
      together with regression of most of the clinical signs of virilization. In
      conclusion, our patient showed a severe virilization developed after menopause;
      hormonal investigations suggested a gonadotropin dependent ovarian
      hyperandrogenism, confirmed by histological examination; the presence of
      luteinized cells in the ovarian stroma was responsible for hyperandrogenism, as
      confirmed by the immunoperoxidase technique.

PMID- 9585390
TI  - Diabetes mellitus and myocardial infarction: a time to act or a time to wait?

PMID- 9585389
TI  - Wishing a dream came true: DHEA as a rejuvenating treatment?

PMID- 9585391
TI  - Managing the diabetic patient with acute myocardial infarction.
AB  - The diabetic patient has a substantially increased in-hospital mortality after
      acute myocardial infarction, which is around twice that of non-diabetic subjects.
      A number of interventions can substantially improve this outcome. The use of
      thrombolytic therapy reduces case fatality proportionately to a similar degree to
      that in non-diabetic patients, but because of the higher background risk,
      absolute benefits are substantially greater. In the world literature, there is
      just one reported case of intraocular haemorrhage after thrombolysis in a
      diabetic patient, and that resolved in 3 weeks, meaning that anxieties around
      theoretical adverse effects of thrombolysis should not preclude its use. There is
      no evidence regarding the advantages of any one thrombolytic agent in these
      subjects. Aspirin treatment again has similar benefits to those in non-diabetic
      subjects, and should be administered at presentation. Some evidence suggests that
      a higher dose of aspirin should be used in diabetic, compared to non-diabetic,
      patients. Finally, the DIGAMI Study has shown that insulin and glucose infusion
      during the hospital admission, followed by multiple injection therapy thereafter,
      reduces mortality by around one-third, both at 12 months and at around 3 1/2
      years. Whether these advantages are because of improved early or late glycaemic
      control, or because of withdrawal of sulphonylureas, is still unclear, but this
      uncertainty should not stand in the way of introducing policies for insulin
      infusion in all diabetic patients admitted with acute myocardial infarction.

PMID- 9585392
TI  - Which drugs benefit diabetic patients for secondary prevention of myocardial
      infarction? DARTS/MEMO Collaboration.
AB  - Diabetic patients have increased mortality following myocardial infarction. We
      review the evidence for benefit in diabetic patients, of the major drug groups
      used as secondary prevention. Beta blockers: meta-analyses suggest a reduction in
      mortality of 35% with beta blockers. Diabetic patients should receive beta
      blockers post myocardial infarction. In many patients, the benefits of beta
      blockers will outweigh relative contraindications. Aspirin: meta-analyses of
      antiplatelet therapy in high-risk subjects have shown substantial benefits.
      Aspirin should be prescribed for secondary prevention. Lipid lowering with
      statins: subgroup analyses of the major secondary prevention trials show
      substantial benefits across a wide range of baseline cholesterol and LDL levels.
      These drugs should be prescribed as secondary prevention to patients with
      diabetes whose total cholesterol is > 4.0 mmol(-1). Angiotensin converting enzyme
      inhibitors (ACEIs): the few subgroup analyses that exist from ACEI trials suggest
      that diabetic and non-diabetic patients derive similar benefits. Diabetic
      subjects who have systolic dysfunction after myocardial infarction should receive
      ACEIs. Treatment combination: data exist to suggest that most of these drugs
      produce benefit independently. CONCLUSION: diabetic patients benefit from
      secondary prevention with drug treatment as much as, or more than, non-diabetic
      patients.

PMID- 9585393
TI  - Beta-cell deterioration determines the onset and rate of progression of secondary
      dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast
      Diet Study.
AB  - Secondary failure of plasma glucose control following initial successful response
      to diet therapy may be due to dietary indiscretion, or to progression of the
      intrinsic diabetic condition. We report a 10-year prospective natural history
      study of 432 newly diagnosed diabetic patients aged 40-69 years undertaken to
      assess the effect of intensive dietary management, where patients were
      transferred to insulin, or oral hypoglycaemic therapy (tolbutamide, metformin) by
      predetermined criteria of weight and plasma glucose. Secondary failure to diet
      therapy occurred in 41 patients in years 2-4, 67 patients in years 5-7, and 51
      patients in years 8-10; 173 patients remained on diet alone until death or the
      end of the study. Continuation on diet alone was associated with a lower ongoing
      fasting plasma glucose, greater beta-cell function assessed by an oral glucose
      tolerance test at 6 months, and increasing age. The rate of rise of fasting
      plasma glucose was inversely related to the duration of successful dietary
      therapy, but mean weight remained constant in all groups while on diet alone. The
      ongoing fall in beta-cell function assessed by HOMA modelling closely mirrored
      the progressive rise in fasting plasma glucose: there was no change in mean
      insulin sensitivity in any of the groups.

PMID- 9585394
TI  - UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over
      six years. UK Prospective Diabetes Study (UKPDS) Group.
AB  - Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on
      sulphonylurea therapy convert to insulin progressively as the sulphonylureas
      'fail'. The rate of failure and the features of those who fail have been poorly
      described. To assess secondary failure rates of sulphonylureas, we report on the
      responses in 1305 patients with newly diagnosed Type 2 DM randomly allocated to
      therapy with either chlorpropamide or glibenclamide in the UK Prospective
      Diabetes Study (UKPDS). These patients were initially treated by diet for 3
      months and had a fasting plasma glucose > 6 mmol l(-1); mean age 53 (SD 9) years;
      BMI 26.8 (SD 5.0) kg m(-2); and median fasting plasma glucose 9.1 (7.6-12.5
      quartiles) mmol l(-1). If their fasting plasma glucose subsequently rose above
      15.0 mmol l(-1), or they developed hyperglycaemic symptoms, additional
      hypoglycaemic therapy was given: metformin, ultratard insulin, and soluble
      insulin as required. By 6 years, 44% had required additional therapy. Of those
      randomized to glibenclamide, 48% required additional therapy by 6 years, compared
      with 40% of those allocated to chlorpropamide (p < 0.01). Sixty-one per cent,
      39%, and 23%, respectively, of patients with fasting plasma glucose > or = 10.0
      mmol l(-1), > or = 7.8 mmol l(-1) to < 10.0 mmol l(-1) and < 7.8 mmol l(-1) at
      randomization required additional therapy (p < 0.001). In the initial 3 years,
      non-obese subjects (BMI < 30 kg m(-2)) were more likely to require additional
      therapy than obese patients (BMI > or = 30 kg m(-2)) (43% vs 53% at 6 years; p <
      0.001). Modelled beta-cell function showed that those with lower function were
      more likely to fail (p < 0.0001). Thus sulphonylureas fail as a therapeutic agent
      at rates which are dependent both on the phenotype at presentation and perhaps on
      the agent used initially. Higher failure rates were found in those with higher
      glucose concentrations, those who were younger, those with lower beta-cell
      reserve and those randomized to glibenclamide compared with chlorpropamide.

PMID- 9585395
TI  - Glycaemic control and cardiovascular risk factors in type 2 diabetes: a
      population-based study.
AB  - The objective of this study was to estimate the prevalence of poor glycaemic
      control and cardiovascular risk factors in an Italian population-based cohort of
      subjects with Type 2 diabetes mellitus (DM). Out of a cohort of 1967 subjects
      (estimated completeness of ascertainment 80%), 1574 (80%) were investigated, and
      adherence to targets for control of the European NIDDM Policy Group assessed.
      Prevalence of poor glycemic control (HbA1c > = 8) was 47.7%. Obesity was present
      in 23.4% of the cohort, hypertension in 83.4%, hypertriglyceridaemia (>2.26 mM)
      in 19.3%, hypercholesterolaemia (>6.46 mM) in 25.5%, and low HDL-cholesterol
      (<0.90 mM in men and <1.03 mM in women) in 13.7%. Only 153 (9.7%) subjects were
      free from other disorders. Subjects were treated as follows: 26.2% exclusively by
      general practitioners; 13.3%, 69.9%, 10.9%, and 5.9% with diet, oral
      hypoglycaemic drugs, insulin, and both, respectively. Multiple linear regression
      analysis showed associations between HbA1c and fibrinogen (p < 0.001), total
      cholesterol (p = 0.006), and triglycerides (p = 0.04), independent of age, sex,
      duration of diabetes, and antidiabetic treatment. Neither BMI nor blood pressure
      were associated with HbA1c. In conclusion, this Italian population-based cohort
      of subjects with Type 2 DM showed a high prevalence of poor glycaemic control,
      high consumption of oral hypoglycaemic drugs, and an independent association
      between glycaemic control and cardiovascular risk factors (fibrinogen, total
      cholesterol, and triglycerides). The presence of obesity or hypertension was not
      significantly associated with glycaemic control.

PMID- 9585397
TI  - Polymorphisms of platelet glycoproteins in relation to macrovascular disease in
      type 2 diabetes mellitus.
AB  - We set out to determine the genotype distributions of the PI(A) polymorphism of
      platelet glycoprotein IIIa, the HPA-3 polymorphism of platelet glycoprotein IIb,
      and the variable number tandem repeat (VNTR) polymorphism of platelet
      glycoprotein Ib in subjects with Type 2 diabetes mellitus (Type 2 DM) with (n =
      125) and without (n = 90) a clinical history of macrovascular disease. In 215
      white European subjects with Type 2 DM, presence of coronary artery disease was
      determined as a clinical history of angina, myocardial infarction (MI), coronary
      angioplasty or coronary artery by-pass grafting. Presence of peripheral vascular
      disease was defined as a clinical history of intermittent claudication with
      confirmatory vascular ultrasound or angiography, intermittent claudication with
      undetectable foot pulses and no history of arthralgia or surgery for leg
      ischaemia, confirmed by reference to medical case notes. Polymorphisms were
      detected by polymerase chain reaction amplification of DNA. There was no
      difference in the genotype distributions of subjects with and without
      macrovascular disease. In subjects with a first MI before the age of 60 years (n
      = 26), there was a 38% incidence of PI(A2) compared to 29% in subjects free from
      clinically evident macrovascular disease, but this difference did not reach
      statistical significance. This study does not support the hypothesis that
      polymorphisms of platelet glycoproteins, in particular the PI(A) polymorphism of
      platelet glycoprotein IIIa, play an important role in the pathogenesis of
      macrovascular disease in subjects with Type 2 DM.

PMID- 9585396
TI  - Rate and mode of death during five years of follow-up among patients with acute
      chest pain with and without a history of diabetes mellitus.
AB  - In order to determine the effect of diabetes on the mortality rate and mode of
      death during 5 years of follow-up among patients who came to the emergency
      department with acute chest pain or other symptoms suggestive of acute myocardial
      infarction (AMI), all patients thus presenting to one single hospital during a
      period of 21 months were followed for 5 years. In total 5230 patients were
      included, of whom 402 (8%) had a history of diabetes. Patients with diabetes
      differed from those without by being older, having a higher prevalence of
      previously diagnosed cardiovascular diseases, having less symptoms of chest pain
      and more symptoms of acute severe heart failure, and more electrocardiographic
      (ECG) abnormalities on admission. Diabetic patients had a 5-year mortality of
      53.5% as compared with 23.3% among non-diabetic patients (p < 0.001; adjusted
      risk ratio 1.60; 95% confidence limits 1.35-1.90). Among diabetic patients the
      following appeared as independent predictors of death: age (p < 0.001), ST
      segment elevation on admission (P < 0.001), a history of myocardial infarction (p
      < 0.05), and a non-pathological ECG on admission (p < 0.001). We conclude that
      among diabetic patients admitted to the emergency department with acute chest
      pain or other symptoms suggestive of AMI more than 50% are dead 5 years later.
      Future research should focus on interventions in order to reduce their mortality.

PMID- 9585398
TI  - Enhancement of soluble CD23 serum levels and cell-surface CD23-expression in
      subjects at increased risk of type 1 diabetes mellitus and in diabetic patients.
AB  - The low affinity receptor for IgE, CD23, is expressed on lymphocytes among other
      cell types. The purpose of the present study was to assess serum sCD23 levels and
      CD23 expression on peripheral blood mononuclear cells (PBMC) in people at
      increased risk of developing Type 1 diabetes mellitus and in diabetic patients.
      Serum sCD23 levels were significantly higher in first-degree relatives of Type 1
      patients (median: 3.2 U ml(-1)) (p < 0.001) and in newly diagnosed (median: 3.3 U
      ml(-1)) (p < 0.001) and long-standing (median: 2.5 U ml(-1)) (p = 0.01) Type 1
      diabetic patients than in controls (median: 1.2 U ml(-1)). Newly diagnosed
      patients showed higher levels than those with long-standing disease (p = 0.026).
      Moreover the percentage of B cells expressing CD23 were significantly higher in
      first-degree relatives (median: 48.6%) (p < 0.001) and in newly diagnosed
      (median: 58%) (p < 0.001) and long-standing (median: 44.8%) (p = 0.03) Type 1
      diabetic patients than in controls (median: 28.5%). The increased sCD23 levels
      and the increased number of cells expressing CD23 observed in subjects at
      increased risk of Type 1 diabetes and diabetic patients may be indicators of Th2
      activity in Type 1 diabetes.

PMID- 9585399
TI  - NEFA elevation during a hyperglycaemic clamp enhances insulin secretion.
AB  - Elevated non-esterified fatty acid (NEFA) levels may influence insulin secretion
      and contribute to the development of Type 2 DM. We investigated the effects of
      acute NEFA elevation in controls (n = 6) and subjects predisposed to Type 2 DM (n
      = 6) on basal insulin levels, and following glucose and arginine stimulation.
      Each subject had one study with a triglyceride (TG) plus heparin infusion
      (elevated NEFA levels) and another with normal saline. Twenty minutes after the
      TG or saline infusion began a glucose bolus was given and 10 min later a 90-min
      hyperglycaemic clamp (approximately 9 mmol l(-1)) was started. Intravenous
      arginine was given at 110 min. Elevated NEFA levels (approximately 4000 micromol
      l(-1)) did not enhance basal or first phase glucose stimulated insulin levels.
      During hyperglycaemia, NEFA elevation further increased insulin levels in both
      groups by 20-44% (p < 0.05) and C-peptide levels by 17-25% (p < 0.05). The post
      arginine insulin levels during hyperglycaemia were increased by 45% in the Type 2
      DM-risk group (p < 0.02). The glucose infusion rate maintaining matched
      hyperglycaemia was similar during NEFA elevation and for saline control for both
      groups. We conclude that acute elevation of NEFA levels enhances glucose and non
      glucose-induced insulin secretion.

PMID- 9585400
TI  - Prevalence of diabetes mellitus and associated cardiovascular risk factors in an
      adult urban population in Paraguay.
AB  - A cross-sectional study was conducted on a 20-74-year-old population in an urban
      white-Hispanic population in Paraguay to determine the prevalence of diabetes
      mellitus (DM), impaired glucose tolerance (IGT), and associated cardiovascular
      disease (CVD) risk factors. In total 1606 subjects completed the study (response
      rate 80.3%; 1094 women, 512 men). The overall prevalences were: DM 6.5%, IGT
      11.3%, hypertension 17.1%, and obesity 31.6% with more obesity in women (35.7% vs
      22.8%, p < 0.05). Age-standardized prevalences were: DM 6.5%, IGT 13.5% in
      females and DM 5.5%, IGT 7.2% in males. DM and IGT subjects had two or more CV
      risk factors significantly more often than the normal population. In conclusion,
      DM, IGT, hypertension, and obesity are common in this South American Hispanic
      urban population, particularly in women. Public health measures, such as
      lifestyle education, are required to decrease these noncommunicable diseases.

PMID- 9585402
TI  - Mobile retinal screening in Britain.

PMID- 9585403
TI  - Diabetic ketoacidosis in children.

PMID- 9585401
TI  - Factors associated with clinic non-attendance in adults with type 1 diabetes
      mellitus.
AB  - In order to examine the causes of non-attendance in a diabetic clinic, a 1-year
      retrospective casenote review of 259 diabetic patients with no evidence of major
      complications was undertaken. Frequency of clinic attendance, clinic non
      attendance, and glycaemic control (HbA1c) were recorded. In a sub-sample of 82
      patients, more detailed demographic data was obtained via questionnaire. During
      the previous year 39% of patients had failed to attend the clinic on at least one
      occasion and 10% were recurrent non-attenders. Non-attenders had a significantly
      higher mean HbA1c compared with those who did attend (8.1 +/- 2.2 vs 7.6 +/-
      1.6%; p = 0.03). They were also significantly younger (mean age 27 + 7 vs 29 +/-
      9 yrs; p = 0.02) and had a significantly shorter duration of diabetes (12 +/- 8
      vs 15 +/- 10 yrs; p = 0.02). Attendance did not differ according to gender or age
      of onset of diabetes. Sub-sample analysis showed that smokers, those with
      children at home, and single parents were all more likely to default from their
      appointments. Non-attendance is a significant problem at our diabetic clinic,
      however, by addressing the reasons why patients fail to attend clinic we hope to
      develop strategies to encourage regular attendance. This may be translated into
      improved glycaemic control and ultimately reduce the risk of late diabetic
      complications.

PMID- 9585404
TI  - Myocardial infarction on a 17-year-old diabetic adolescent.

PMID- 9585405
TI  - Evidence for a role of CLIP-170 in the establishment of metaphase chromosome
      alignment.
AB  - CLIPs (cytoplasmic linker proteins) are a class of proteins believed to mediate
      the initial, static interaction of organelles with microtubules. CLIP-170, the
      CLIP best characterized to date, is required for in vitro binding of endocytic
      transport vesicles to microtubules. We report here that CLIP-170 transiently
      associates with prometaphase chromosome kinetochores and codistributes with
      dynein and dynactin at kinetochores, but not polar regions, during mitosis. Like
      dynein and dynactin, a fraction of the total CLIP-170 pool can be detected on
      kinetochores of unattached chromosomes but not on those that have become aligned
      at the metaphase plate. The COOH-terminal domain of CLIP-170, when transiently
      overexpressed, localizes to kinetochores and causes endogenous full-length CLIP
      170 to be lost from the kinetochores, resulting in a delay in prometaphase.
      Overexpression of the dynactin subunit, dynamitin, strongly reduces the amount of
      CLIP-170 at kinetochores suggesting that CLIP-170 targeting may involve the
      dynein/dynactin complex. Thus, CLIP-170 may be a linker for cargo in mitosis as
      well as interphase. However, dynein and dynactin staining at kinetochores are
      unaffected by this treatment and further overexpression studies indicate that
      neither CLIP-170 nor dynein and dynactin are required for the formation of
      kinetochore fibers. Nevertheless, these results strongly suggest that CLIP-170
      contributes in some way to kinetochore function in vivo.

PMID- 9585406
TI  - Nucleocytoplasmic shuttling factors including Ran and CRM1 mediate nuclear export
      of NFAT In vitro.
AB  - We have developed a permeabilized cell assay to study the nuclear export of the
      shuttling transcription factor NFAT, which contains a leucine-rich export signal.
      The assay uses HeLa cells that are stably transfected with NFAT fused to the
      green fluorescent protein (GFP). Nuclear export of GFP-NFAT in digitonin
      permeabilized cells occurs in a temperature- and ATP-dependent manner and can be
      quantified by flow cytometry. In vitro NFAT export requires the GTPase Ran, which
      is released from cells during the digitonin permeabilization. At least one
      additional rate-limiting export factor is depleted from permeabilized cells by a
      preincubation at 30 degrees C in the absence of cytosol. This activity can be
      provided by cytosolic or nucleoplasmic extracts in a subsequent export step.
      Using this assay, we have purified a second major export activity from cytosol.
      We found that it corresponds to CRM1, a protein recently reported to be a
      receptor for certain leucine-rich export sequences. CRM1 appears to be imported
      into the nucleus by a Ran-dependent mechanism that is distinct from conventional
      signaling pathways. Considered together, our studies directly demonstrate by
      fractionation and reconstitution that nuclear export of NFAT is mediated by
      multiple nucleocytoplasmic shuttling factors, including Ran and CRM1.

PMID- 9585407
TI  - Nuclear localization of cyclin B1 controls mitotic entry after DNA damage.
AB  - Mitosis in human cells is initiated by the protein kinase Cdc2-cyclin B1, which
      is activated at the end of G2 by dephosphorylation of two inhibitory residues,
      Thr14 and Tyr15. The G2 arrest that occurs after DNA damage is due in part to
      stabilization of phosphorylation at these sites. We explored the possibility that
      entry into mitosis is also regulated by the subcellular location of Cdc2-cyclin
      B1, which is suddenly imported into the nucleus at the end of G2. We measured the
      timing of mitosis in HeLa cells expressing a constitutively nuclear cyclin B1
      mutant. Parallel studies were performed with cells expressing Cdc2AF, a Cdc2
      mutant that cannot be phosphorylated at inhibitory sites. Whereas nuclear cyclin
      B1 and Cdc2AF each had little effect under normal growth conditions, together
      they induced a striking premature mitotic phenotype. Nuclear targeting of cyclin
      B1 was particularly effective in cells arrested in G2 by DNA damage, where it
      greatly reduced the damage-induced G2 arrest. Expression of nuclear cyclin B1 and
      Cdc2AF also resulted in significant defects in the exit from mitosis. Thus,
      nuclear targeting of cyclin B1 and dephosphorylation of Cdc2 both contribute to
      the control of mitotic entry and exit in human cells.

PMID- 9585408
TI  - The beta subunit of the Sec61 complex facilitates cotranslational protein
      transport and interacts with the signal peptidase during translocation.
AB  - The Sec61 complex is the central component of the protein translocation apparatus
      of the ER membrane. We have addressed the role of the beta subunit (Sec61beta)
      during cotranslational protein translocation. With a reconstituted system, we
      show that a Sec61 complex lacking Sec61beta is essentially inactive when
      elongation and membrane targeting of a nascent chain occur at the same time. The
      translocation process is perturbed at a step where the nascent chain would be
      inserted into the translocation channel. However, if sufficient time is given for
      the interaction of the nascent polypeptide with the mutant Sec61 complex,
      translocation is almost normal. Thus Sec61beta kinetically facilitates
      cotranslational translocation, but is not essential for it. Using chemical cross
      linking we show that Sec61beta not only interacts with subunits of the Sec61
      complex but also with the 25-kD subunit of the signal peptidase complex (SPC25),
      thus demonstrating for the first time a tight interaction between the SPC and the
      Sec61 complex. Interestingly, the cross-links between Sec61beta and SPC25 and
      between Sec61beta and Sec61alpha depend on the presence of membrane-bound
      ribosomes, suggesting that these interactions are induced when translocation is
      initiated. We propose that the SPC is transiently recruited to the translocation
      site, thus enhancing its activity.

PMID- 9585409
TI  - Positive charges determine the topology and functionality of the transmembrane
      domain in the chloroplastic outer envelope protein Toc34.
AB  - The chloroplastic outer envelope protein Toc34 is inserted into the membrane by a
      COOH-terminal membrane anchor domain in the orientation Ncyto-Cin. The insertion
      is independent of ATP and a cleavable transit sequence. The cytosolic domain of
      Toc34 does not influence the insertion process and can be replaced by a different
      hydrophilic reporter peptide. Inversion of the COOH-terminal, 45-residue segment,
      including the membrane anchor domain (Toc34Cinv), resulted in an inverted
      topology of the protein, i.e., Nin-Ccyto. A mutual exchange of the charged amino
      acid residues NH2- and COOH-proximal of the hydrophobic alpha-helix indicates
      that a double-positive charge at the cytosolic side of the transmembrane alpha
      helix is the sole determinant for its topology. When the inverted COOH-terminal
      segment was fused to the chloroplastic precursor of the ribulose-1,5-bisphosphate
      carboxylase small subunit (pS34Cinv), it engaged the transit sequence-dependent
      import pathway. The inverted peptide domain of Toc34 functions as a stop transfer
      signal and is released out of the outer envelope protein translocation machinery
      into the lipid phase. Simultaneously, the NH2-terminal part of the hybrid
      precursor remained engaged in the inner envelope protein translocon, which could
      be reversed by the removal of ATP, demonstrating that only an energy-dependent
      force but no further ionic interactions kept the precursor in the import
      machinery.

PMID- 9585410
TI  - Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization
      and activation through caveolae-like domains.
AB  - The mechanism by which cholera toxin (CT) is internalized from the plasma
      membrane before its intracellular reduction and subsequent activation of adenylyl
      cyclase is not well understood. Ganglioside GM1, the receptor for CT, is
      predominantly clustered in detergent-insoluble glycolipid rafts and in caveolae,
      noncoated, cholesterol-rich invaginations on the plasma membrane. In this study,
      we used filipin, a sterol-binding agent that disrupts caveolae and caveolae-like
      structures, to explore their role in the internalization and activation of CT in
      CaCo-2 human intestinal epithelial cells. When toxin internalization was
      quantified, only 33% of surface-bound toxin was internalized by filipin-treated
      cells within 1 h compared with 79% in untreated cells. However, CT activation as
      determined by its reduction to form the A1 peptide and CT activity as measured by
      cyclic AMP accumulation were inhibited in filipin-treated cells. Another sterol
      binding agent, 2-hydroxy-beta-cyclodextrin, gave comparable results. The cationic
      amphiphilic drug chlorpromazine, an inhibitor of clathrin-dependent, receptor
      mediated endocytosis, however, affected neither CT internalization, activation,
      nor activity in contrast to its inhibitory effects on diphtheria toxin
      cytotoxicity. As filipin did not inhibit the latter, the two drugs appeared to
      distinguish between caveolae- and coated pit-mediated processes. In addition to
      its effects in CaCo-2 cells that express low levels of caveolin, filipin also
      inhibited CT activity in human epidermoid carcinoma A431 and Jurkat T lymphoma
      cells that are, respectively, rich in or lack caveolin. Thus, filipin inhibition
      correlated more closely with alterations in the biochemical characteristics of CT
      bound membranes due to the interactions of filipin with cholesterol rather than
      with the expressed levels of caveolin and caveolar structure. Our results
      indicated that the internalization and activation of CT was dependent on and
      mediated through cholesterol- and glycolipid-rich microdomains at the plasma
      membrane rather than through a specific morphological structure and that these
      glycolipid microdomains have the necessary components required to mediate
      endocytosis.

PMID- 9585412
TI  - Lipid domain structure of the plasma membrane revealed by patching of membrane
      components.
AB  - Lateral assemblies of glycolipids and cholesterol, "rafts," have been implicated
      to play a role in cellular processes like membrane sorting, signal transduction,
      and cell adhesion. We studied the structure of raft domains in the plasma
      membrane of non-polarized cells. Overexpressed plasma membrane markers were
      evenly distributed in the plasma membrane. We compared the patching behavior of
      pairs of raft markers (defined by insolubility in Triton X-100) with pairs of
      raft/non-raft markers. For this purpose we cross-linked glycosyl
      phosphatidylinositol (GPI)-anchored proteins placental alkaline phosphatase
      (PLAP), Thy-1, influenza virus hemagglutinin (HA), and the raft lipid ganglioside
      GM1 using antibodies and/or cholera toxin. The patches of these raft markers
      overlapped extensively in BHK cells as well as in Jurkat T-lymphoma cells.
      Importantly, patches of GPI-anchored PLAP accumulated src-like protein tyrosine
      kinase fyn, which is thought to be anchored in the cytoplasmic leaflet of raft
      domains. In contrast patched raft components and patches of transferrin receptor
      as a non-raft marker were sharply separated. Taken together, our data strongly
      suggest that coalescence of cross-linked raft elements is mediated by their
      common lipid environments, whereas separation of raft and non-raft patches is
      caused by the immiscibility of different lipid phases. This view is supported by
      the finding that cholesterol depletion abrogated segregation. Our results are
      consistent with the view that raft domains in the plasma membrane of non
      polarized cells are normally small and highly dispersed but that raft size can be
      modulated by oligomerization of raft components.

PMID- 9585411
TI  - Ganglioside structure dictates signal transduction by cholera toxin and
      association with caveolae-like membrane domains in polarized epithelia.
AB  - In polarized cells, signal transduction by cholera toxin (CT) requires apical
      endocytosis and retrograde transport into Golgi cisternae and perhaps ER (Lencer,
      W.I., C. Constable, S. Moe, M. Jobling, H.M. Webb, S. Ruston, J.L. Madara, T.
      Hirst, and R. Holmes. 1995. J. Cell Biol. 131:951-962). In this study, we tested
      whether CT's apical membrane receptor ganglioside GM1 acts specifically in toxin
      action. To do so, we used CT and the related Escherichia coli heat-labile type II
      enterotoxin LTIIb. CT and LTIIb distinguish between gangliosides GM1 and GD1a at
      the cell surface by virtue of their dissimilar receptor-binding B subunits. The
      enzymatically active A subunits, however, are homologous. While both toxins bound
      specifically to human intestinal T84 cells (Kd approximately 5 nM), only CT
      elicited a cAMP-dependent Cl- secretory response. LTIIb, however, was more potent
      than CT in eliciting a cAMP-dependent response from mouse Y1 adrenal cells (toxic
      dose 10 vs. 300 pg/well). In T84 cells, CT fractionated with caveolae-like
      detergent-insoluble membranes, but LTIIb did not. To investigate further the
      relationship between the specificity of ganglioside binding and partitioning into
      detergent-insoluble membranes and signal transduction, CT and LTIIb chimeric
      toxins were prepared. Analysis of these chimeric toxins confirmed that toxin
      induced signal transduction depended critically on the specificity of ganglioside
      structure. The mechanism(s) by which ganglioside GM1 functions in signal
      transduction likely depends on coupling CT with caveolae or caveolae-related
      membrane domains.

PMID- 9585413
TI  - Myosin heavy chains IIa and IId are functionally distinct in the mouse.
AB  - Myosin in adult murine skeletal muscle is composed primarily of three adult fast
      myosin heavy chain (MyHC) isoforms. These isoforms, MyHC-IIa, -IId, and -IIb, are
      >93% identical at the amino acid level and are broadly expressed in numerous
      muscles, and their genes are tightly linked. Mice with a null mutation in the
      MyHC-IId gene have phenotypes that include growth inhibition, muscle weakness,
      histological abnormalities, kyphosis (spinal curvature), and aberrant kinetics of
      muscle contraction and relaxation. Despite the lack of MyHC-IId, IId null mice
      have normal amounts of myosin in their muscles because of compensation by the
      MyHC-IIa gene. In each muscle examined from IId null mice, there was an increase
      in MyHC-IIa- containing fibers. MyHC-IIb content was unaffected in all muscles
      except the masseter, where its expression was extinguished in the IId null mice.
      Cross-sectional fiber areas, total muscle cross-sectional area, and total fiber
      number were affected in ways particular to each muscle. Developmental expression
      of adult MyHC genes remained unchanged in IId null mice. Despite this universal
      compensation of MyHC-IIa expression, IId null mice have severe phenotypes. We
      conclude that despite the similarity in sequence, MyHC-IIa and -IId have unique
      roles in the development and function of skeletal muscle.

PMID- 9585414
TI  - An ordered inheritance strategy for the Golgi apparatus: visualization of mitotic
      disassembly reveals a role for the mitotic spindle.
AB  - During mitosis, the ribbon of the Golgi apparatus is transformed into dispersed
      tubulo-vesicular membranes, proposed to facilitate stochastic inheritance of this
      low copy number organelle at cytokinesis. Here, we have analyzed the mitotic
      disassembly of the Golgi apparatus in living cells and provide evidence that
      inheritance is accomplished through an ordered partitioning mechanism. Using a
      Sar1p dominant inhibitor of cargo exit from the endoplasmic reticulum (ER), we
      found that the disassembly of the Golgi observed during mitosis or microtubule
      disruption did not appear to involve retrograde transport of Golgi residents to
      the ER and subsequent reorganization of Golgi membrane fragments at ER exit
      sites, as has been suggested. Instead, direct visualization of a green
      fluorescent protein (GFP)-tagged Golgi resident through mitosis showed that the
      Golgi ribbon slowly reorganized into 1-3-micron fragments during G2/early
      prophase. A second stage of fragmentation occurred coincident with nuclear
      envelope breakdown and was accompanied by the bulk of mitotic Golgi
      redistribution. By metaphase, mitotic Golgi dynamics appeared to cease.
      Surprisingly, the disassembly of mitotic Golgi fragments was not a random event,
      but involved the reorganization of mitotic Golgi by microtubules, suggesting that
      analogous to chromosomes, the Golgi apparatus uses the mitotic spindle to ensure
      more accurate partitioning during cytokinesis.

PMID- 9585416
TI  - A dynein light chain is essential for the retrograde particle movement of
      intraflagellar transport (IFT).
AB  - Several enzymes, including cytoplasmic and flagellar outer arm dynein, share an
      Mr 8,000 light chain termed LC8. The function of this chain is unknown, but it is
      highly conserved between a wide variety of organisms. We have identified deletion
      alleles of the gene (fla14) encoding this protein in Chlamydomonas reinhardtii.
      These mutants have short, immotile flagella with deficiencies in radial spokes,
      in the inner and outer arms, and in the beak-like projections in the B tubule of
      the outer doublet microtubules. Most dramatically, the space between the doublet
      microtubules and the flagellar membrane contains an unusually high number of
      rafts, the particles translocated by intraflagellar transport (IFT) (Kozminski,
      K.G., P.L. Beech, and J.L. Rosenbaum. 1995. J. Cell Biol. 131:1517-1527). IFT is
      a rapid bidirectional movement of rafts under the flagellar membrane along
      axonemal microtubules. Anterograde IFT is dependent on a kinesin whereas the
      motor for retrograde IFT is unknown. Anterograde IFT is normal in the LC8 mutants
      but retrograde IFT is absent; this undoubtedly accounts for the accumulation of
      rafts in the flagellum. This is the first mutation shown to specifically affect
      retrograde IFT; the fact that LC8 loss affects retrograde IFT strongly suggests
      that cytoplasmic dynein is the motor that drives this process. Concomitant with
      the accumulation of rafts, LC8 mutants accumulate proteins that are components of
      the 15-16S IFT complexes (Cole, D.G., D.R. Deiner, A.L. Himelblau, P.L. Beech,
      J.C. Fuster, and J.L. Rosenbaum. 1998. J. Cell Biol. 141:993-1008), confirming
      that these complexes are subunits of the rafts. Polystyrene microbeads are still
      translocated on the surface of the flagella of LC8 mutants, indicating that the
      motor for flagellar surface motility is different than the motor for retrograde
      IFT.

PMID- 9585415
TI  - Analysis of the Saccharomyces spindle pole by matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry.
AB  - A highly enriched spindle pole preparation was prepared from budding yeast and
      fractionated by SDS gel electrophoresis. Forty-five of the gel bands that
      appeared enriched in this fraction were analyzed by high-mass accuracy matrix
      assisted laser desorption/ ionization (MALDI) peptide mass mapping combined with
      sequence database searching. This identified twelve of the known spindle pole
      components and an additional eleven gene products that had not previously been
      localized to the spindle pole. Immunoelectron microscopy localized eight of these
      components to different parts of the spindle. One of the gene products, Ndc80p,
      shows homology to human HEC protein (Chen, Y., D.J. Riley, P-L. Chen, and W-H.
      Lee. 1997. Mol. Cell Biol. 17:6049-6056) and temperature-sensitive mutants show
      defects in chromosome segregation. This is the first report of the identification
      of the components of a large cellular organelle by MALDI peptide mapping alone.

PMID- 9585417
TI  - Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles
      contain proteins required for ciliary assembly in Caenorhabditis elegans sensory
      neurons.
AB  - We previously described a kinesin-dependent movement of particles in the flagella
      of Chlamydomonas reinhardtii called intraflagellar transport (IFT) (Kozminski,
      K.G., K.A. Johnson, P. Forscher, and J.L. Rosenbaum. 1993. Proc. Natl. Acad. Sci.
      USA. 90:5519-5523). When IFT is inhibited by inactivation of a kinesin, FLA10, in
      the temperature-sensitive mutant, fla10, existing flagella resorb and new
      flagella cannot be assembled. We report here that: (a) the IFT-associated FLA10
      protein is a subunit of a heterotrimeric kinesin; (b) IFT particles are composed
      of 15 polypeptides comprising two large complexes; (c) the FLA10 kinesin-II and
      IFT particle polypeptides, in addition to being found in flagella, are highly
      concentrated around the flagellar basal bodies; and, (d) mutations affecting
      homologs of two of the IFT particle polypeptides in Caenorhabditis elegans result
      in defects in the sensory cilia located on the dendritic processes of sensory
      neurons. In the accompanying report by Pazour, G.J., C.G. Wilkerson, and G.B.
      Witman (1998. J. Cell Biol. 141:979-992), a Chlamydomonas mutant (fla14) is
      described in which only the retrograde transport of IFT particles is disrupted,
      resulting in assembly-defective flagella filled with an excess of IFT particles.
      This microtubule- dependent transport process, IFT, defined by mutants in both
      the anterograde (fla10) and retrograde (fla14) transport of isolable particles,
      is probably essential for the maintenance and assembly of all eukaryotic motile
      flagella and nonmotile sensory cilia.

PMID- 9585418
TI  - scully, an essential gene of Drosophila, is homologous to mammalian mitochondrial
      type II L-3-hydroxyacyl-CoA dehydrogenase/amyloid-beta peptide-binding protein.
AB  - The characterization of scully, an essential gene of Drosophila with
      phenocritical phases at embryonic and pupal stages, shows its extensive homology
      with vertebrate type II L-3-hydroxyacyl-CoA dehydrogenase/ERAB. Genomic rescue
      demonstrates that four different lethal mutations are scu alleles, the molecular
      nature of which has been established. One of them, scu3127, generates a
      nonfunctional truncated product. scu4058 also produces a truncated protein, but
      it contains most of the known functional domains of the enzyme. The other two
      mutations, scu174 and scuS152, correspond to single amino acid changes. The
      expression of scully mRNA is general to many tissues including the CNS; however,
      it is highest in both embryonic gonadal primordia and mature ovaries and testes.
      Consistent with this pattern, the phenotypic analysis suggests a role for scully
      in germ line formation: mutant testis are reduced in size and devoid of maturing
      sperm, and mutant ovarioles are not able to produce viable eggs. Ultrastructural
      analysis of mutant spermatocytes reveals the presence of cytoplasmic lipid
      inclusions and scarce mitochondria. In addition, mutant photoreceptors contain
      morphologically aberrant mitochondria and large multilayered accumulations of
      membranous material. Some of these phenotypes are very similar to those present
      in human pathologies caused by beta-oxidation disorders.

PMID- 9585419
TI  - The alpha5beta1 integrin mediates elimination of amyloid-beta peptide and
      protects against apoptosis.
AB  - The amyloid-beta peptide (Abeta) can mediate cell attachment by binding to beta1
      integrins through an arg-his-asp sequence. We show here that the alpha5beta1
      integrin, a fibronectin receptor, is an efficient binder of Abeta, and mediates
      cell attachment to nonfibrillar Abeta. Cells engineered to express alpha5beta1
      internalized and degraded more added Abeta1-40 than did alpha5beta1-negative
      control cells. Deposition of an insoluble Abeta1-40 matrix around the alpha5beta1
      expressing cells was reduced, and the cells showed less apoptosis than the
      control cells. Thus, the alpha5beta1 integrin may protect against Abeta
      deposition and toxicity, which is a course of Alzheimer's disease lesions.

PMID- 9585420
TI  - Detection of a novel intraneuronal pool of insoluble amyloid beta protein that
      accumulates with time in culture.
AB  - The amyloid-beta peptide (Abeta) is produced at several sites within cultured
      human NT2N neurons with Abeta1-42 specifically generated in the endoplasmic
      reticulum/intermediate compartment. Since Abeta is found as insoluble deposits in
      senile plaques of the AD brain, and the Abeta peptide can polymerize into
      insoluble fibrils in vitro, we examined the possibility that Abeta1-40, and
      particularly the more highly amyloidogenic Abeta1-42, accumulate in an insoluble
      pool within NT2N neurons. Remarkably, we found that formic acid extraction of the
      NT2N cells solubilized a pool of previously undetectable Abeta that accounted for
      over half of the total intracellular Abeta. Abeta1-42 was more abundant than
      Abeta1-40 in this pool, and most of the insoluble Abeta1-42 was generated in the
      endoplasmic reticulum/intermediate compartment pathway. High levels of insoluble
      Abeta were also detected in several nonneuronal cell lines engineered to
      overexpress the amyloid-beta precursor protein. This insoluble intracellular pool
      of Abeta was exceptionally stable, and accumulated in NT2N neurons in a time
      dependent manner, increasing 12-fold over a 7-wk period in culture. These novel
      findings suggest that Abeta amyloidogenesis may be initiated within living
      neurons rather than in the extracellular space. Thus, the data presented here
      require a reexamination of the prevailing view about the pathogenesis of Abeta
      deposition in the AD brain.

PMID- 9585421
TI  - Mammalian granulocyte-macrophage colony-stimulating factor receptor expressed in
      primary avian hematopoietic progenitors: lineage-specific regulation of
      proliferation and differentiation.
AB  - The cytokine Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) regulates
      proliferation, differentiation, and apoptosis during myelopoiesis and
      erythropoiesis. Structure-function relationships of GM-CSF interactions with its
      receptor (GM-R), the biochemistry of GM-R signal transduction, and GM-CSF action
      in vivo are relatively well understood. Much less is known, however, about GM-R
      function in primary hematopoietic cells. In this paper we show that expression of
      the human GM-R in a heterologous cell system (primary avian erythroid and myeloid
      cells) confirms respective results in murine or human cell lines, but also
      provides new insights how the GM-R regulates progenitor proliferation and
      differentiation. As expected, the hGM-CSF stimulated myeloid progenitor
      proliferation and differentiation and enhanced erythroid progenitor proliferation
      during terminal differentiation. In the latter cells, however, the hGM-R only
      partially substituted for the activities of the erythropoietin receptor (EpoR).
      It failed to replace the EpoR in its cooperation with c-Kit to induce long-term
      proliferation of erythroid progenitors. Furthermore, the hGM-R alpha chain
      specifically interfered with EpoR signaling, an activity neither seen for the
      betac subunit of the receptor complex alone, nor for the alpha chain of the
      closely related Interleukin-3 receptor. These results point to a novel role of
      the GM-R alpha chain in defining cell type-specific functions of the GM-R.

PMID- 9585422
TI  - 6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high
      endothelium, is an agonist for the MIP-3beta receptor CCR7.
AB  - The beta chemokine known as 6-C-kine, secondary lymphoid-tissue chemokine (SLC),
      TCA4, or Exodus-2 (herein referred to as 6CK/SLC) can trigger rapid integrin
      dependent arrest of lymphocytes rolling under physiological shear and is highly
      expressed by high endothelial venules, specialized vessels involved in lymphocyte
      homing from the blood into lymph nodes and Peyer's patches. We show that 6CK/SLC
      is an agonist for the lymphocyte chemoattractant receptor, CCR7 (EBI-1, BLR-2),
      previously described as a receptor for the related beta chemokine MIP-3beta (ELC
      or Exodus-3). Moreover, 6CK/SLC and MIP-3beta attract the same major populations
      of circulating lymphocytes, including naive and memory T cells > B cells (but not
      natural killer cells); desensitization to MIP-3beta inhibits lymphocyte
      chemotaxis to 6CK/SLC but not to the alpha chemokine SDF-1 (stromal cell-derived
      factor); and 6CK/SLC competes for MIP-3beta binding to resting mouse lymphocytes.
      The findings suggest that the majority of circulating lymphocytes respond to
      6CK/SLC and MIP-3beta in large part through their common receptor CCR7 and that
      these molecules may be important mediators of physiological lymphocyte
      recirculation in vivo.

PMID- 9585424
TI  - Modulation of integrin activity is vital for morphogenesis.
AB  - Cells can vary their adhesive properties by modulating the affinity of integrin
      receptors. The activation and inactivation of integrins by inside-out mechanisms
      acting on the cytoplasmic domains of the integrin subunits has been demonstrated
      in platelets, lymphocytes, and keratinocytes. We show that in the embryo, normal
      morphogenesis requires the alpha subunit cytoplasmic domain to control integrin
      adhesion at the right times and places. PS2 integrin (alphaPS2betaPS) adhesion is
      normally restricted to the muscle termini, where it is required for attaching the
      muscles to the ends of other muscles and to specialized epidermal cells.
      Replacing the wild-type alphaPS2 with mutant forms containing cytoplasmic domain
      deletions results in the rescue of the majority of defects associated with the
      absence of the alphaPS2 subunit, however, the mutant PS2 integrins are
      excessively active. Muscles containing these mutant integrins make extra muscle
      attachments at aberrant positions on the muscle surface, disrupting the muscle
      pattern and causing embryonic lethality. A gain- of-function phenotype is not
      observed in the visceral mesoderm, showing that regulation of integrin activity
      is tissue-specific. These results suggest that the alphaPS2 subunit cytoplasmic
      domain is required for inside-out regulation of integrin affinity, as has been
      seen with the integrin alphaIIbbeta3.

PMID- 9585423
TI  - Epithelial V-like antigen (EVA), a novel member of the immunoglobulin
      superfamily, expressed in embryonic epithelia with a potential role as homotypic
      adhesion molecule in thymus histogenesis.
AB  - Thymus development depends on a complex series of interactions between thymocytes
      and the stromal component of the organ. To identify regulated genes during this
      codependent developmental relationship, we have applied an RNA fingerprinting
      technique to the analysis of thymus expansion and maturation induced in
      recombinase-deficient mice injected with anti-CD3 antibodies. This approach led
      us to the identification of a gene encoding a new member of the immunoglobulin
      superfamily, named epithelial V-like antigen (EVA), which is expressed in thymus
      epithelium and strongly downregulated by thymocyte developmental progression.
      This gene is expressed in the thymus and in several epithelial structures early
      in embryogenesis. EVA is highly homologous to the myelin protein zero and, in
      thymus-derived epithelial cell lines, is poorly soluble in nonionic detergents,
      strongly suggesting an association to the cytoskeleton. Its capacity to mediate
      cell adhesion through a homophilic interaction and its selective regulation by T
      cell maturation might imply the participation of EVA in the earliest phases of
      thymus organogenesis.

PMID- 9585426
TI  - The new kid on the block--a whole genome mouse radiation hybrid panel.

PMID- 9585425
TI  - NF-kappaB mediates alphavbeta3 integrin-induced endothelial cell survival.
AB  - The alphavbeta3 integrin plays a fundamental role during the angiogenesis process
      by inhibiting endothelial cell apoptosis. However, the mechanism of inhibition is
      unknown. In this report, we show that integrin-mediated cell survival involves
      regulation of nuclear factor-kappa B (NF-kappaB) activity. Different
      extracellular matrix molecules were able to protect rat aorta- derived
      endothelial cells from apoptosis induced by serum withdrawal. Osteopontin and
      beta3 integrin ligation rapidly increased NF-kappaB activity as measured by gel
      shift and reporter activity. The p65 and p50 subunits were present in the shifted
      complex. In contrast, collagen type I (a beta1-integrin ligand) did not induce NF
      kappaB activity. The alphavbeta3 integrin was most important for osteopontin
      mediated NF-kappaB induction and survival, since adding a neutralizing anti-beta3
      integrin antibody blocked NF-kappaB activity and induced endothelial cell death
      when cells were plated on osteopontin. NF-kappaB was required for osteopontin-
      and vitronectin-induced survival since inhibition of NF-kappaB activity with
      nonphosphorylatable IkappaB completely blocked the protective effect of
      osteopontin and vitronectin. In contrast, NF-kappaB was not required for
      fibronectin, laminin, and collagen type I-induced survival. Activation of NF
      kappaB by osteopontin depended on the small GTP-binding protein Ras and the
      tyrosine kinase Src, since NF-kappaB reporter activity was inhibited by Ras and
      Src dominant-negative mutants. In contrast, inhibition of MEK and PI3-kinase did
      not affect osteopontin-induced NF-kappaB activation. These studies identify NF
      kappaB as an important signaling molecule in alphavbeta3 integrin-mediated
      endothelial cell survival.

PMID- 9585427
TI  - Genetic dissection of "OLETF", a rat model for non-insulin-dependent diabetes
      mellitus.
AB  - To elucidate the genetic factors underlying non-insulin-dependent diabetes
      mellitus (NIDDM), we performed genome-wide quantitative trait locus (QTL)
      analysis, using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat
      is an excellent animal model of NIDDM because the features of the disease closely
      resemble human NIDDM. Genetic dissection with two kinds of F2 intercross progeny,
      from matings between the OLETF rat and non-diabetic control rats F344 or BN,
      allowed us to identify on Chromosome (Chr) 1 a major QTL associated with features
      of NIDDM that was common to both crosses. We also mapped two additional
      significant loci, on Chrs 7 and 14, in the (OLETF x F344)F2 cross alone, and
      designated these three loci as Diabetes mellitus, OLETF type Dmo 1, Dmo2 and Dmo3
      respectively. With regard to suggestive QTLs, we found loci on Chrs 10, 11, and
      16 that were common to both crosses, as well as loci on Chrs 5 and 12 in the
      (OLETF x F344)F2 cross and on Chrs 4 and 13 in the (OLETF x BN)F2 cross. Our
      results showed that NIDDM in the OLETF rat is polygenic and demonstrated that
      different genetic backgrounds could affect "fitness" for QTLs and produce
      different phenotypic effects from the same locus.

PMID- 9585428
TI  - A missense mutation in the endothelin-B receptor gene is associated with Lethal
      White Foal Syndrome: an equine version of Hirschsprung disease.
AB  - Lethal White Foal Syndrome is a disease associated with horse breeds that
      register white coat spotting patterns. Breedings between particular spotted
      horses, generally described as frame overo, produce some foals that, in contrast
      to their parents, are all white or nearly all white and die shortly after birth
      of severe intestinal blockage. These foals have aganglionosis characterized by a
      lack of submucosal and myenteric ganglia from the distal small intestine to the
      large intestine, similar to human Hirschsprung Disease. Some sporadic and
      familial cases of Hirschsprung Disease are due to mutations in the endothelin B
      receptor gene (EDNRB). In this study, we investigate the role of EDNRB in Lethal
      White Foal Syndrome. A cDNA for the wild-type horse endothelin-B receptor gene
      was cloned and sequenced. In three unrelated lethal white foals, the EDNRB gene
      contained a 2-bp nucleotide change leading to a missense mutation (I118K) in the
      first transmembrane domain of the receptor, a highly conserved region of this
      protein among different species. Seven additional unrelated lethal white foal
      samples were found to be homozygous for this mutation. No other homozygotes were
      identified in 138 samples analyzed, suggesting that homozygosity was restricted
      to lethal white foals. All (40/40) horses with the frame overo pattern (a
      distinct coat color pattern that is a subset of overo horses) that were tested
      were heterozygous for this allele, defining a heterozygous coat color phenotype
      for this mutation. Horses with tobiano markings included some carriers,
      indicating that tobiano is epistatic to frame overo. In addition, horses were
      identified that were carriers but had no recognized overo coat pattern phenotype,
      demonstrating the variable penetrance of the mutation. The test for this mutant
      allele can be utilized in all breeds where heterozygous animals may be
      unknowingly bred to each other including the Paint Horse, Pinto horse, Quarter
      Horse, Miniature Horse, and Thoroughbred.

PMID- 9585429
TI  - A potential association between the BM 1500 microsatellite and fat deposition in
      beef cattle.
AB  - The obese gene was hypothesized as a candidate gene for fat characteristics in
      beef cattle. The BM 1500 microsatellite, near the obese gene, was characterized
      in 158 purebred beef bulls for which carcass trait information was available.
      Four breeds were included in the analyses-Angus, Charolais, Hereford, and
      Simmental. Four alleles were found. Lengths were approximately 138, 147, 149, and
      140 bp with genotypic frequencies of 0.47, 0.44, 0.09, and 0.003 respectively.
      The carcass traits %rib fat, %rib lean, average fat, and grade fat were found to
      be significantly associated with the different alleles. The presence of the 138
      bp allele in the genotype of an animal is correlated with higher levels of fat,
      whereas the 147-bp allele has the opposite effect. The 149-bp allele was found in
      low numbers, and a homozygote was never identified. Hereford and Angus bulls had
      the greatest frequencies of 138-bp alleles (Hereford = 0.57, Angus = 0.59), while
      Charolais and Simmental had a greater proportion of 147-bp alleles (Charolais =
      0.54, Simmental = 0.58). This information may aid cattle producers in selecting
      cattle for markets that differ in the amount of fat required.

PMID- 9585430
TI  - Comparative study of the genomic organization of DNA repeats within the 5'
      flanking region of the natural resistance-associated macrophage protein gene
      (NRAMP1) between humans and great apes.
AB  - The human NRAMP1 gene located on Chromosome (Chr) region 2q35 is a candidate gene
      for increased risk of infection by several intracellular macrophage parasites,
      including M. tuberculosis and M. leprae. In search for a possible mutational hot
      spot, we have analyzed a 3.5-kb region 5' to NRAMP1 that is highly enriched for
      DNA repeat sequences. The repeat sequences could be grouped into one Mer element
      and six Alu elements, representing five Alu subfamilies, that had integrated in
      the same DNA region during successive rounds of Alu retropositional activity.
      Comparative sequence analysis of the Alu cluster region in humans, chimpanzee
      (Pan paniscus), and gorilla (Gorilla gorilla) revealed only modest sequence
      variability and failed to detect any evidence for genomic instability of the
      highly repetitive DNA region. These results show that sequence length variants in
      the Alu-flanking regions as well as nucleotide substitutions are the most common
      genomic variations even in a region of extreme Alu-clustering. Moreover, the high
      degree of sequence conservation among three primate species argues against the
      Alu cluster being the site of frequent genomic rearrangements or other frequent
      genetic events that might influence NRAMP1 expression.

PMID- 9585431
TI  - Orangutan alpha-satellite monomers are closely related to the human consensus
      sequence.
AB  - Alpha-satellite is a family of tandemly repeated DNA found at the centromeric
      regions of all human and primate chromosomes. Human alpha-satellite subsets are
      largely chromosome-specific and have been further grouped into four
      suprachromosomal families (SFs), each characterized by a unique set of monomeric
      types. Although chimpanzee and gorilla alpha-satellites share sufficient sequence
      similarity to fit the established SFs, the assumption that the derived human
      alpha-satellite consensus and monomeric types represent the sequence of ancestral
      repeats remains unestablished. By using oligonucleotide primers specific for a
      conserved region of human alpha-satellite DNA, we have PCR amplified, cloned, and
      characterized alpha-satellite sequences from the orangutan genome. Nucleotide
      sequence analysis demonstrated that orangutan alpha-satellite is formed by a
      single monomeric type that is significantly closer in percentage of sequence
      identity (mean = 92%, range = 89-96%) to the overall consensus of human alpha
      satellite than to the monomeric types corresponding to the four SFs. Use of
      cloned sequences as hybridization probes to orangutan genomic DNA digested with a
      panel of restriction enzymes showed that most orangutan alpha-satellite subsets
      are characterized by a monomeric construction. The subset homologous to clone
      PPY2-5 is organized in distinct higher-order repeat structures consisting of 18
      adjacent monomers. By FISH two clones, PPY3-4 and PPY3-5, proved to be specific
      for the alpha-satellite on the orangutan homologs of human Chromosomes (Chrs) 10
      and 8, respectively. Our data indicate that there was an ancestral monomeric type
      displaying high sequence similarity to the overall human consensus from which the
      different great ape and human subsets and SFs may have originated.

PMID- 9585432
TI  - Genetic mapping of the mouse Rab7 gene and pseudogene and of the human RAB7
      homolog.
AB  - Rab proteins are small GTP-ases localized to distinct membrane compartments in
      eukaryotic cells and regulating specific steps of intracellular vesicular
      membrane traffic. The Rab7 protein is localized to the late endosomal compartment
      and controls late steps of endocytosis. We have isolated, by library screening,
      the 5' region, including the promoter, of the mouse Rab7 gene and a Rab7
      pseudogene. We have mapped, by genetic linkage analysis, the mouse Rab7 gene on
      Chromosome (Chr) 6 and the Rab7-ps1 pseudogene on Chr 9, where the Rab7 gene has
      been previously reported to map. By radiation hybrid mapping, we have located the
      human RAB7 gene on Chr 3, in a region homologous to the mouse Chr 6, where the
      Rab7 gene maps.

PMID- 9585433
TI  - Mouse beta defensin-1 is a functional homolog of human beta defensin-1.
AB  - Defensin are 3-4 kDa antimicrobial peptides of which three distinct families have
      been identified; alpha-defensin, beta-defensins, and insect defensins. Recent
      investigations have shown that beta-defensins are present in the human airways
      and may be relevant to the pathogenesis of cystic fibrosis (CF) lung disease. We
      report here the further characterization of a recently identified mouse beta
      defensin gene, Defb1, sometimes referred to as mBD-1, which is homologous to the
      human airway beta defensin hBD-1. We report that Defb1 is expressed in a variety
      of tissues including the airways and, similar to hBD-1, is not upregulated by
      lipopolysaccharide (LPS). Defb1 was found to consist of two small exons separated
      by a 16-kb intron and cytogenetic, and physical mapping linked it to the alpha
      defensin gene cluster on mouse Chromosome (Chr) 8. Functional studies demonstrate
      that, like hBD-1, Defb1 demonstrates a salt-sensitive antimicrobial activity
      against Pseudomonas aeruginosa. Of relevance to CF lung disease is the fact that
      neither the hBD-1 nor the mBD-1 peptides are active against Burkholderia cepacia.

PMID- 9585434
TI  - Cloning, characterization, and chromosomal assignment of the human ortholog of
      murine Zfp-37, a candidate gene for Nager syndrome.
AB  - In an effort to identify putative transcription factors involved in chondrocyte
      differentiation during human endochondral bone formation, a human fetal cartilage
      specific cDNA library was screened with a degenerate oligonucleotide probe
      corresponding to a conserved stretch of eight amino acids from the zinc finger
      region of the Drosophila Kruppel gene family of DNA-binding proteins. Using this
      strategy, we have identified a novel zinc finger gene ZFP-37. ZFP-37 corresponds
      to a putative transcription factor containing 12 tandemly repeated zinc finger
      motifs and a Kruppel-associated box (KRAB) domain. The KRAB domain has been
      reported to function as a transcriptional repressor and is located in the amino
      terminus, while the zinc finger repeats are positioned at the carboxy-terminal
      end of ZFP-37. Gene mapping with a somatic cell hybrid panel and fluorescence in
      situ hybridization (FISH) localized ZFP-37 to human Chr 9q32. The gene is
      expressed at low level as a 3.2-kb mRNA in several tissues including fetal human
      cartilage. Sequence comparison revealed that ZFP-37 may represent the human
      homolog of the mouse gene Zfp-37. The map location and expression pattern suggest
      ZFP-37 as a candidate gene for a craniofacial-limb malformation, Nager syndrome
      (acrofacial dysostosis).

PMID- 9585435
TI  - Cloning and chromosomal localization of a new member of the bHLH/PAS
      transcription factor family.
AB  - Here we report the cloning and primary characterization of TIC, a new member of
      the bHLH/PAS domain family of transcription factors. Northern blot analysis
      indicates that the 3.3-kb Tic mRNA is widely expressed. A polyclonal antibody
      against TIC identifies multiple protein species in most cell lines and tissues
      tested, suggesting that alternative splicing may result in the production of
      protein isoforms. Interspecies backcross and FISH mapping have been used to
      localize the Tic gene to mouse Chromosome (Chr) 7 F2-F3, given the locus name
      Arntl. FISH mapping was also used to localize the human gene to Chr 11p15.

PMID- 9585436
TI  - White-based brown (Tyrp1B-w) is a dominant mutation causing reduced hair
      pigmentation owing to a chromosomal inversion.

PMID- 9585437
TI  - Genetic mapping of 10 microsatellites in the t complex region of mouse chromosome
      17.

PMID- 9585438
TI  - Mapping of the human and murine X11-like genes (APBA2 and apba2), the murine Fe65
      gene (Apbb1), and the human Fe65-like gene (APBB2): genes encoding
      phosphotyrosine-binding domain proteins that interact with the Alzheimer's
      disease amyloid precursor protein.

PMID- 9585439
TI  - Localization of the rat M1 muscarinic receptor gene to chromosome 1q43-51.

PMID- 9585440
TI  - Sublocalizing the centromeric region in linkage groups from three metacentric rat
      chromosomes by FISH.

PMID- 9585442
TI  - Six transcripts map within 200 kilobases of the myotonic dystrophy expanded
      repeat.

PMID- 9585441
TI  - Mapping to 1q23 of the human gene (NDUFS2) encoding the 49-kDa subunit of the
      mitochondrial respiratory Complex I and immunodetection of the mature protein in
      mitochondria.

PMID- 9585443
TI  - Enrichment of a LINE subfamily in a single chromosomal region in Peromyscus.

PMID- 9585444
TI  - The lengths of undiscovered conserved segments in comparative maps.

PMID- 9585445
TI  - One-Stage Coronary Bypass and Abdominal Aortic Aneurysm Repair
AB  - A group of 29 patients with simultaneous coronary disease and abdominal aortic
      aneurysm were treated following two protocols: Group I, 16 patients had coronary
      bypass surgery and then abdominal aortic aneurysm repair at a later date. This
      required two hospitalizations and two separate surgeries. Group II, 11 patients,
      underwent coronary bypass surgery and repair of abdominal aortic aneurysm (AAA)
      in one sitting. Group III, 2 patients, had PTCA prior to AAA repair. There were
      3.1 bypass grafts implanted (Group I), vs 2.9 (Groups II) (ns). All abdominal
      aneurysms were infrarenal and 22 patients had straight tube graft replacement
      (76%), and seven bifurcated grafts. Two patients with angina also had symptomatic
      AAA. Period of hospitalization, morbidity, mortality, time of total recovery,
      hospital costs, and apprehension of patients were analyzed. There was one death
      in Group I. In this group, the total recovery time was 4.8 months vs 2.4 months
      for Group II. Hospitalization time was 16.2 days in Group I vs 8.2 days in Group
      II. The hospital costs were significantly higher in Group I with an average of
      $58,950 vs $46,553 in Group II. No deaths occurred in Group II. It is recommended
      that if a patient with severe coronary disease requiring surgery also presents
      with an AAA of more than 5 cm, he/she should have both conditions operated on in
      one session rather than staggering the procedures. It saves time, cost, anxiety,
      and is well tolerated.

PMID- 9585446
TI  - Left Ventricular Systolic and Diastolic Functions in Patients With Sickle Cell
      Anemia
AB  - The aim of this study was to evaluate the left ventricular systolic and diastolic
      functions in patients with sickle cell anemia. Fifty-four patients (34 male, 20
      female, mean age 22.6 +/- 7.3 years) and 23 healthy persons (12 male, 11 female,
      mean age 26.7 +/- 6.8 years) were studied. After clinical examination and routine
      biochemical evaluation by a hematologist, patients with sickle cell anemia were
      admitted to the study. M-mode and 2-dimensional and Doppler echocardiographic
      measurements of patients and controls were performed according to criteria of the
      American Echocardiography Society. The values of the patient groups were compared
      with the values of normal healthy subjects (controls). Left ventricular systolic
      and diastolic diameters of sickle cell patients were greater than those of
      controls (p < 0.001). All of the sickle cell anemia patients had reduced systolic
      cardiac function (EF: 0.57 +/- 0.1 vs 0.63 +/- 0.06 and FS: 0.30 +/- 0.06 vs 0.34
      +/- 0.04, p < 0.02) and abnormal diastolic left ventricular function parameters
      compared with the control group (IRT: 114 +/- 20 msec vs 65 +/- 7 msec, p <
      0.0001; E/A ratio: 1.2 +/- 0.5 vs 1.6 +/- 0.04, p < 0.01). Left ventricular mass
      (LVM) was greater in patients than in controls (222 +/- 78 g vs 177 +/- 46 g, p <
      0.01). Left ventricular systolic and diastolic functions were abnormal in
      patients with sickle cell anemia, and the left ventricular mass was greater in
      the patients compared with controls.

PMID- 9585447
TI  - The Role of Polytetrafluoroethylene Graft Material in Buerger's Disease
AB  - The early and long-term results of polytetrafluoroethylene (PTFE) grafts in
      different anatomical locations were evaluated in 14 patients with Buerger's
      disease (thromboangiitis obliterans). During a 10-year period, 2160 patients with
      peripheral vascular disease were treated and, in 258, the diagnosis of Buerger's
      disease was made. Fourteen of these 258 patients underwent revascularization with
      PTFE grafts. In a follow-up period, up to 8 years patency rates were as follows:
      aorto/ilofemoral bypass 80%, femoropopliteal bypass 40%, femorocrural bypass 50%
      with a cumulative patency rate of 57.1%, and limb salvage rate of 88.9%. Because
      of the diverse nature and small number of the operations, the numerical results
      are not amenable to statistical analysis, but 88.9% limb salvage rate is
      satisfying in Buerger's disease. To the best of our knowledge, this is the first
      report on the use of PTFE grafts in Buerger's disease and it validates limb
      salvage even below the inguinal ligament.

PMID- 9585448
TI  - What's New in Lymphedema Therapy in America?
AB  - There is much confusion among American medical professionals regarding the
      treatment of lymphedema. Much of it has to do with the fact that lymphedema
      "falls between the cracks" of all standard specialties in modern American
      practice. Partially for this reason and because of a general misconception among
      American physicians that lymphedema is not a "serious" problem, the condition has
      been virtually ignored and deprioritized for many decades. This study is intended
      to clarify the confusion and reasons for apathy toward the subject of lymphedema
      and its treatment. Lymphedema, for the most part ignored or poorly treated in the
      United States, is currently being effectively treated by complete (or complex)
      decongestive physiotherapy (CDP) in many American facilities. CDP was introduced
      to the United States by the author in 1989 and is a gentle, effective, cost
      effective, safe, and noninvasive treatment. It is and must be performed by
      specially trained therapists under the supervision of lymphologists with
      expertise in lymphedema, its diagnosis, treatment, complications, and natural
      history. This article describes the author's experience in treating 1000 upper
      and 1000 lower extremity lymphedema patients by the CDP method. These patients
      were treated between 1989 and 1995 for an average of 25 treatments, each patient
      returning for a follow-up examination 1 year after the completion of his or her
      course of treatment. The variables recorded in this study were as follows: the
      patient's sex, type of lymphedema, and volumetric reduction achieved immediately
      following treatment and as measured 1 year after treatment. The therapy and
      follow-up procedures are explained in detail and examples (before and after
      photos) of actual cases are included. Based on the results of this study and
      others, it is the author's opinion that CDP therapy is superior to any surgical
      procedures currently being used and to the pneumatic pump therapies often
      erroneously recommended for this condition.

PMID- 9585449
TI  - Hemodynamic and Inotropic Effects of Antiarrhythmic Drugs Used to Treat
      Paroxysmal Supraventricular Arrhythmias
AB  - Episodes of sustained paroxysmal supraventricular tachycardias can be terminated
      by antiarrhythmic drugs given intravenously. The cardiodepressive effects of
      these drugs are an important limitation of this therapeutic procedure. The dose
      dependent circulatory and myocardial effects of the nucleoside adenosine (0.5,
      2.0, 5.0 mg/kg/minute) and the class I antiarrhythmic drug ajmaline (1.0, 2.0,
      4.0 mg/kg) were investigated in 73 open-chest rats. Hemodynamic measurements in
      the intact circulation and isovolumic registrations (peak isovolumic left
      ventricular systolic pressure and peak isovolumic dP/dtmax) were compared with
      saline controls. Adenosine has a short-lasting, negative, chronotropic effect
      that causes a dose-dependent reduction of cardiac output (-34%, -54%, -65% vs
      control). The peak isovolumic left ventricular systolic pressure (LVSP) is not
      changed significantly by adenosine (-6%, -4%, +5% vs control). The negative
      chronotropic effect of ajmaline with consecutive reduction of cardiac output is
      less pronounced (cardiac output: -18%, -20%, -38% vs control). The highest dose
      of ajmaline causes a significant reduction of peak isovolumic LVSP (-2%, -1%, -7%
      vs control). Adenosine has an impressive negative chronotropic effect with a
      consequent marked decrease of cardiac output. The reduction of cardiac output by
      adenosine is more pronounced compared with ajmaline. Nevertheless, adenosine has
      in contrast to ajmaline-no cardiodepressive effects in vivo.

PMID- 9585450
TI  - Thoracic Outlet Syndrome: Follow-up on 33 Cases with Regard to Vascular
      Compression
AB  - This follow-up study on 33 operations performed for thoracic outlet syndrome
      (TOS) proves high efficiency in relieving neurological and arterial symptoms,
      whereas benefit to venous compression is somewhat less. Twenty-six patients
      (average age was 36 years) were operated on for TOS, seven of them on both sides.
      There was a higher incidence in females. All patients showed neurological
      symptoms. In 15, operations on various entrapment syndromes of the upper
      extremity were performed previously. Six patients presented with an incomplete
      resection of the first rib. Arterial compression symptoms were evident in 15
      cases, symptoms of venous compression in 14 limbs. All patients underwent a
      resection of the first rib, bilateral in seven cases, using the axillary and
      supraclavicular approach. In seven patients, a cervical rib and scalenus muscles
      were resected additionally, in three patients bilaterally. In two cases a
      neurolysis of the brachial plexus was performed. Using the supraclavicular
      approach, no complications occurred. In one early patient using the transaxillary
      approach to a postoperative hemothorax required a revision. Neurological results
      after surgery showed a total release in 26 limbs (n = 33). In 14 limbs (n = 15)
      with arterial compression symptoms and in 6 (n = 14) with symptoms of venous
      compression the operation showed a curative effect.

PMID- 9585451
TI  - Congenital and Atherosclerotic (Acquired) Coronary Artery Aneurysms: Coronary
      Angiographic and Morphologic Observations in 10 Patients
AB  - Coronary angiographic observations in 10 patients with coronary artery aneurysms
      (CAAs) are reported. Four patients had atherosclerotic (acquired) and six had
      congenital CAAs. The mean age of patients with acquired CAAs was higher (64.7
      years) compared with the congenital group (53.2 years). Ipsilateral myocardial
      infarction (MI) occurred in three of four patients with acquired CAAs but MI was
      not located on the same side as the aneurysm-bearing coronary artery
      (contralateral) in two patients with the congenital variety. In the patients with
      congenital CAAs, an aneurysm predilection site was observed in the proximal
      portion of the aneurysm-bearing vessel. Dual and multiple aneurysms were more
      common in the acquired CAAs. Although congenital CAAs were sizeable, the small
      sized atherosclerotic CAAs developed complications more frequently. During an
      average follow-up of 7.9 years, only one patient died of a noncardiac cause and
      another developed recurrent uncomplicated non-Q wave lateral MI. Both subjects
      had atherosclerotic CAAs. In our series, no rupture or sudden death occurred.
      Coronary artery bypass grafting (CABG) was performed in three patients with
      acquired and in one patient with congenital CAAs. In the latter patient,
      simultaneous ligation of the congenital aneurysm associated with a coronary
      arteriovenous fistula was performed. Regarding antiplatelet and anticoagulant
      policy for the whole group, three patients were on aspirin, four were on
      acenocoumarol, and in another three subjects with congenital CAAs, a medical
      regimen was followed. Larger series, however, are required in order to elucidate
      further angiographic characteristics of acquired vs congenital CAAs.

PMID- 9585452
TI  - Surgical Correction and Prognostic Factors for Ascending Aortic Lesions Involving
      Coronary Arteries
AB  - The prognostic factors following aortic root reconstruction were studied in 19
      patients including 13 with annuloaortic ectasia (AAE) and 6 without AAE (non
      AAE). The preoperative diagnosis of six non-AAE patients was a dissecting
      aneurysm in five of the patients and supravalvular aortic stenosis associated
      with stenosis of the right coronary ostia in one patients. In the AAE group, the
      Bentall's method was initially selected in 11 patients and the Cabrol's method in
      the remaining 2 patients. In the non-AAE group, ascending aortic replacement was
      performed in 4 patients, patch plasty of the ascending aorta in 1 patient, and
      entry closure in the other patient. In this group, aorto-coronary bypass grafting
      using a saphenous vein graft was performed in 4 patients, ostioplasty of the
      right coronary artery (RCA) in 1, and the Bentall's method in 1. During the
      postoperative acute phase, one AAE patient died of acute myocardial infarction 3
      days after surgery; the remaining 18 patients survived. In the follow-up study, 3
      patients died of cardiac events which included two cardiac failures and one
      arrhythmia. The preoperative left ventricular diameter in the end-diastolic phase
      (LVDd) of 2 AAE patients who died of cardiac failure was 80 mm or larger and the
      left ventricular function remained unchanged after surgery. One non-AAE patient
      who underwent RCA ostioplasty suddenly died of arrhythmia. Postanastomotic
      leakage around the left coronary ostia associated with the patent Cabrol's trick
      occurred in 1 AAE patient and mitral valve regurgitation occurred in the other
      non-AAE patient. Reoperation using Cabrol's procedure and mitral valve
      replacement were performed for these 2 patients, respectively. Preoperative low
      cardiac function and large LVDd may influence the late results in AAE patients,
      therefore, earlier operations should be recommended.

PMID- 9585453
TI  - Fibromuscular Dysplasia of the Aorta Presenting as Multiple Recurrent Thoracic
      Aneurysms
AB  - A 17-year-old boy, who had undergone resection of aortic coarctation with a large
      saccular aneurysm 10 years previously, developed recurrent aneurysms above and
      below the site of a Gore-Tex interposition graft. These were resected using
      femoral-femoral bypass, and the upper thoracic aorta was replaced with a
      Hemashield Dacron tube. Histology of the aorta showed fibromuscular dysplasia. In
      addition to aortic dissection and aortic rupture, such patients may be at risk of
      forming further aneurysms.

PMID- 9585455
TI  - Postocclusive Reactive Hyperemia During Vascular Reconstruction
AB  - The purpose of this basic investigation was to clarify the postocclusive reactive
      hyperemia during vascular reconstruction using laser Doppler flowmetry (LDF). For
      the fundamental experiment, thirty-nine limbs with arteriosclerosis obliterans
      (ASO) in Stage II according to Fontaine's classification and 33 limbs without
      arterial or venous disease were chosen. In the supine position, a thigh cuff was
      applied to the lower thigh of a subject. Systolic Doppler thigh pressure was
      obtained and thigh/arm pressure index (TPI) was calculated. A LDF probe was then
      fixed to the bottom of the first toe and cutaneous blood flow was measured
      continuously before, during, and after femoral artery occlusion by the thigh
      cuff. The occlusion time was 3 and 6 minutes. For the clinical study, thirty
      three lower limbs with arterial occlusive disease were selected. During the
      vascular surgery, the LDF probe was attached to the bottom of the first toe and
      cutaneous blood flow was monitored continuously before, during, and after the
      vascular clamping. In the fundamental experiment, after the release of the
      occlusion, the maximum blood flow of the reactive hyperemia (peak flow) appeared.
      The period between the release of the occlusion and the peak flow was called the
      peak time. When the occlusion time was longer, the reactive hyperemia appeared
      later and was bigger. When TPI decreased, the peak time lengthened and the peak
      flow after a 6-minute occlusion decreased. In the clinical study, the more severe
      the degree of the preoperative limb ischemia was, the longer was the peak time.
      The longer the intraoperative clamping time, the longer the peak time. In
      conclusion, postocclusive reactive hyperemia during vascular surgery was
      influenced by the degree of the preoperative limb ischemia and the length of the
      vascular clamping time.

PMID- 9585454
TI  - Two Surgically Treated Patients With Severe Symptoms of Takayasu Arteritis
AB  - Takayasu arteritis, also known as the aortitis syndrome, is a panarteritis that
      affects the arcus aorta and its major branches, seen usually in young women. As
      Takayasu arteritis has a progressive nature, surgery is usually indicated only in
      complications of the arteritis. In this report we present two surgically treated
      cases with severe complications of Takayasu arteritis. We also review the
      syndrome.

PMID- 9585456
TI  - Cardiovascular Effects of Bolus-Administered Vasodilators in Elderly Patients
      with Atherosclerotic Disease: A Comparative Study of Nitroglycerin and
      Prostaglandin E1
AB  - To evaluate the hemodynamic effects of vasodilators in elderly patients with
      atherosclerotic disease, systemic hemodynamics were examined during cardiac
      catheterization study. After the intravenous bolus injection of nitroglycerin
      (NTG, 5 ug/kg, n = 20) or prostaglandin E1 (PGE1, 0.2 ug/kg, n = 20), significant
      reduction of mean arterial pressure, pulmonary capillary wedge pressure (PCWP),
      systemic vascular resistance index (SVRI), and rate-pressure product (RPP) was
      observed. In contrast, cardiac index and stroke index were not significantly
      deteriorated in either group. In conclusion, bolus-administered NTG and PGE1 had
      beneficial vasodilating effects without harmful impact on cardiac functions in
      elder patients with atherosclerotic disease.

PMID- 9585457
TI  - Anticoagulant Effects of Argatroban on the Pre-DIC State in Patients with an
      Aortic Aneurysm: A Comparative Study of Heparin
AB  - We compared the efficacy of argatroban, a new synthetic thrombin-specific
      inhibitor, with that of heparin in pre-DIC state patients with abdominal aortic
      aneurysm (AAA). A pre-DIC state was diagnosed by a detection of soluble fibrin
      monomer complex (FM) and increased levels of thrombin-antithrombin III complex
      (TAT) of more than 20 ng/ml. Twelve patients showing a pre-DIC condition were
      treated with argatroban (40 mg/day, n = 6) or heparin (10,000 U/day, n = 6) for 5
      days. Coagulation and fibrinolytic profiles were analyzed before and after drug
      administration. FM became negative in two (33%) patients after the argatroban
      treatment and in all (100%) of the heparin-treated patients. Plasma levels of TAT
      were significantly decreased after the heparin treatment, however, there was no
      significant alteration in this parameter after the argatroban treatment. In
      conclusion, the anticoagulant effects of heparin were superior to those of
      argatroban in controlling the pre-DIC state associated with AAA.

PMID- 9585458
TI  - Clinical Dynamics of Varicose Disease in Patients with High Degree of Venous
      Reflux During Conservative Treatment and After Surgery: 7-Year Follow-Up
AB  - 183 patients (195 limbs) with primary femoral vein reflux were evaluated to
      relate valvular insufficiency and clinical results of elastic compression (68
      limbs), saphenectomy (75 limbs), and valvuloplasty (52 limbs). Duplex scanning
      and calculating of Reflux Volume Index (RI) were performed before surgery and up
      to nine years of follow-up. Strong correlation between hemodynamic changes and
      results of treatment was found. Reulceration and recurrence were found in 74% of
      extremities with increasing leakage and in 14% of extremities with stable valve
      function. All 38 extremities with improved valvular function were free of ulcers
      and recurrent varicose veins. The success of surgical treatment in extremities
      with primary femoral vein reflux is associated with valvular function
      improvement. Elastic compression alone has poor clinical and hemodynamic results.
      Valvuloplasty significantly improves the results of surgical treatment.

PMID- 9585459
TI  - The Effects of Sublingual Administration of Captopril on Parameters of Exercise
      Test and Neurohormonal Activation in Patients With Stable Angina Pectoris
AB  - A prospective randomized, double-blind, and placebo-controlled study was designed
      to investigate the effects of sublingual administration of captopril on the
      parameters of exercise test and neurohormonal activation in patients with stable
      angina pectoris. A total of 31 patients (28 male, 3 female; mean age 55.4 +/- 9.4
      years) took part in the study. Coronary angiography and left ventriculography
      were performed in all cases and the patients were classified according to the
      ejection fraction (EF). Following sublingual placebo or 25 mg captopril, plasma
      levels of renin, angiotensin II, norepinephrine, and serum aldosterone levels
      were measured at rest and maximal exercise. test was performed. Hormone levels
      were remeasured immediately after the exercise. The same procedure was repeated
      the next day using captopril or placebo. Sublingual captopril administration
      increased the time to angina, the time to 1 mm ST depression, maximal exercise
      capacity, maximal exercise duration and decreased maximal ST depression, maximal
      systolic blood pressure, and maximal double product (p < 0.001-0.01). After the
      maximal exercise test following captopril, the % difference of angiotensin II,
      aldosterone, and norepinephrine levels was found to be significant lower and the
      % difference of the renin level was found to be significantly higher than those
      of placebo (p < 0.001). The effects of sublingual captopril on exercise
      parameters were additionally assessed in different left ventricular systolic
      function subgroups. The favorable effects were more prominent in cases with left
      ventricular systolic dysfunction. There were no adverse effects related to
      sublingual captopril use. As a result, sublingual administration of captopril
      improved the parameters of maximal exercise test and suppressed the neurohormonal
      activation during exercise. We suggest that sublingual captopril may be used
      effectively before planned daily activities in patients with stable angina
      pectoris.

PMID- 9585460
TI  - Relationship Between Components of Heart Rate Variability and Doppler
      Echocardiographic Indices of Left Ventricular Systolic Performance in Patients
      with Coronary Artery Disease
AB  - Decreased heart rate variability (HRV) has been reported as prognostic predictor
      in coronary artery disease population. The aim of the study was to assess the
      relationship between cardiac autonomic tone disturbances and the degree of left
      ventricular dysfunction, estimated by 2-dimensional and Doppler echocardiography,
      in patients with coronary artery disease. Forty patients with angiographically
      proven coronary artery disease and 15 age-and sex-matched healthy subjects were
      included into the study (Group I and II, respectively). Routine clinical
      examinations, electrocardiography, coronary angiography, and 2-dimensional and
      Doppler echocardiography with assessment of LV systolic performance were done in
      all the patients and control subjects. Cardiac autonomic function was assessed by
      means of frequency-domain analysis of heart rate variability. The powers of LF
      and HF bands (P1 and P2), their ratio (P1/P2), and the logarithmic expression of
      powers were measured. The patients (Group I) had lower values of parasympathetic
      band of HRV and higher sympathetic activity than the healthy population (Group
      II) (p < 0.0002 for P2 and p < 0.04 for P1/P2 ratio). A positive significant
      correlation was seen between parasympathetic band of HRV and ejection fraction (r
      = 0.61, p < 0.0001), and mean acceleration of aortal flow (r = 0.56, p < 0.0001),
      whereas P1/P2 ratio inversely and significantly correlated with the same
      parameters (r = -0.46, p < 0.002 and r = -0.41, p < 0.008).

PMID- 9585461
TI  - The Incidence of Occult Malignant Diseases in Patients With Deep Venous
      Thrombosis of the Pelvis and Lower Limb
AB  - In 318 patients (155 men, 163 women) with an average age of 58.8 years (range 16
      97 years), a retrospective study was carried out to determine the incidence of
      occult malignancies in patients with deep venous thrombosis affecting the pelvis
      and lower limb, confirmed by phlebography or duplex ultrasonography. It was found
      that, overall, 7.5% of all patients had occult malignant diseases, the most
      common being bronchial carcinoma (16%), colonic and renal carcinomas (12% each),
      and prostatic and pancreatic carcinoma (8% each). Of the patients with occult
      malignancy, 88% were older than 55 years. This fact shows that acute
      phlebothromboses may be a paraneoplastic early syndrome more often than was
      previously thought, and that patients older than 50 should always be screened for
      the presence of a tumor.

PMID- 9585462
TI  - Venous Function in Patients with Venous Disease and Healthy Controls Before and
      After a Bathing Procedure and Subsequent Cold Stimulus
AB  - The object of this study was to determine whether bathing in thermal water
      acutely affects venous function in patients with venous insufficiency.
      Measurements were taken of venous function in patients with leg varicosities and
      healthy subjects before and after a thermal bath and exercise on two days, with
      subsequent application of a cold stimulus on 1 day. A total of 28 patients with
      varicose veins in one or both legs (n = 45 legs) and 30 healthy controls (n = 60
      legs). On 2 consecutive days all subjects underwent a standardized bathing and
      exercise procedure in water at 34 degreesC for 20 minutes. On one day, determined
      randomly for each subject, a cold stimulus was applied to both lower legs after
      bathing. Measurements were done before subjects entered the bath and after the
      completion of bathing (including cold stimulus on one day). Without the cold
      stimulus, venous function of patients and controls did not change. After
      application of the cold stimulus the venous capacity of both patients and
      controls was significantly reduced compared with the basal levels. There was no
      change in maximum venous outflow in the controls, but that of the patient group
      decreased slightly compared with basal levels. Contrary to widespread belief,
      bathing in water at temperatures above 28 degreesC does not adversely affect
      venous function in patients with varicose veins. When applied in moderation (34
      degreesC for 20 minutes) this physical therapy should not be regarded as
      contraindicated in this and related conditions, especially given its known
      hemodynamic benefits. Further studies are required to determine the long-term
      effects of repeated immersion.

PMID- 9585463
TI  - The Incidence of Heparin-Induced Thrombocytopenias
AB  - The incidence of heparin-induced thrombocytopenia (HIT) types I and II was
      investigated retrospectively in 500 heparin-treated patients. In our department
      of internal medicine 500 patients were treated with unfractionated, middle- or
      low-molecular heparin (s.c. or i.v.) during 1995 as inpatients. Excluded were
      patients with other known causes of thrombocytopenia. There were 306 females
      (61%), mean age 76 years (17-98 years) and 194 males (39%), mean age 73 years (24
      93 years). The incidence of HI type I was 4.4% and of HIT type II 0.6% with a
      positive heparin-induced-platelet-activation test (HIPA test). In addition, HIT
      type II was suspected in another 1.4% of cases with negative or missing HIPA
      test. Because of our results on the incidence of HIT type I and type II a close
      control of thrombocyte count during heparin therapy is necessary. In the case of
      HIT type II disease, heparin therapy must be stopped immediately.

PMID- 9585464
TI  - Discrete Type Subaortic Stenosis in Dextrocardia with Situs Inversus Totalis
AB  - This paper presents the case report of a patient with discrete type subaortic
      stenosis in dextrocardia and its associated clinical manifestations.

PMID- 9585465
TI  - Angioplasty of Subclavian Artery Stenosis: Report of Two Cases and Review of the
      Literature
AB  - In this study we present two patients who underwent successful percutaneous
      transluminal angioplasty of a symptomatic left subclavian artery stenosis. We
      have compared our data with the data obtained from the current literature.

PMID- 9585466
TI  - Diagnosis of Abnormal Subclavian Venous Flow by Radionuclide Venography in
      Patients with Permanent Pacemaker
AB  - In this study, we investigated the role of radionuclide venography in the
      diagnosis of abnormal subclavian venous flow due to the lead in patients (pts)
      with permanent pacemakers. The study was conducted with 53 frames in 52
      asymptomatic pts (26 females, mean age 64.5 +/- 15; range 25-89 years). The mean
      time after implant was 67.6 +/- 47.5 months. Technetium 99m pertecnetate (250
      MBq) was given to both antecubital veins simultaneously. The images were acquired
      in 0.25-second frames for 20 seconds. The pts were evaluated visually in terms of
      the activity flow through the subclavian veins bilaterally. The retrograde flow
      in the jugular vein, decrease in flow rate, and subtotal and total obstruction of
      the subclavian veins were accepted as abnormal venous flow patterns. In 17 pts
      with abnormal findings, 10 (58.8%) had retrograde flow in the jugular vein, 4 had
      (23.5%) decreased flow rate, 1 (5.8%) had subtotal and 2 (11.7%) total
      obstruction in the subclavian vein. The mean of the body diameter of the leads
      was significantly greater and the percentage of the silicone-insulated leads was
      higher (76% vs 52%) in the group with abnormal flow. No complication due to the
      procedure was seen. In conclusion, radionuclide venography, a noninvasive method,
      may be used easily and safely to show the venous flow abnormalities due to the
      lead in pts with permanent pacemakers. The abnormal subclavian venous flow was
      especially seen in pts who had larger leads.

PMID- 9585467
TI  - Aortocoronary Vein Bypass in a Patient with Type II Heparin-Associated
      Thrombopenia: A Case Report
AB  - Two types of heparin-associated thrombopenia (HAT) can be distinguished. Patients
      with type II HAT (HAT II) present a particularly difficult management problem
      when they require full anticoagulation. There is no consensus about the proper
      anticoagulation management for patients with HAT II who have to undergo
      cardiopulmonary bypass (CPB). We present a HAT II patient who underwent
      successful aortocoronary saphenous vein grafting. Sodium-danaparoid (SD) was used
      for anticoagulation. The anti-factor Xa level was kept below the values reported
      in the literature for patients undergoing CPB. We did not observe any fibrin
      formation during the time of CPB or any severe postoperative hemorrhage, which is
      frequently described in the literature. We discuss the management of our patient
      with SD intra- and postoperatively.

PMID- 9585468
TI  - Correlation of Atrial Natriuretic Factor and Renin-Aldosterone System With
      Chronic Pulmonary Hypertension Among Residents in a High Altitude
AB  - The study was performed to evaluate right ventricular contractility, plasma renin
      activity, and atrial natriuretic peptide in high altitude pulmonary arterial
      hypertension (HAPH). Sixty-eight patients with signs of pulmonary artery
      hypertension (PPA,syst > 25 mmHg, PPA > 15 mmHg) (Group II) and 40 with normal
      coronary angiograms and normal pulmonary artery pressures (Group I) were included
      in the study. Right heart catheterization with estimation of right ventricular
      and pulmonary artery pressures were performed in all the patients. The blood
      samples were taken from the pulmonary artery for measurement of mean oxygen
      saturatioyn (SaO2), atrial natriuretic factor (ANF) level, plasma renin activity
      (PRA), aldosterone level, and sodium and potassium concentrations. Statistical
      analysis was performed using unpaired Student's t test and linear regression
      analysis. The patients with HAPH had higher pulmonary artery pressures (PPA,syst,
      PPA, PPA,diast), total pulmonary resistance (Rpulm,tot), and right ventricular
      systolic pressure (PRv,syst). The significant correlation was found between ANF
      and PRA with right ventricular contractility indices and pulmonary vascular
      resistance.

PMID- 9585469
TI  - Nuclear magnetic resonance solution structures of covalent aromatic amine-DNA
      adducts and their mutagenic relevance.

PMID- 9585470
TI  - Large-scale synthesis of the catechol metabolites of diethylstilbestrol and
      hexestrol.
AB  - Diethylstilbestrol (DES) and hexestrol (HES) are carcinogenic synthetic
      estrogens. The major metabolites of these compounds are their catechol
      derivatives, 3'-OH-DES and 3'-OH-HES. Oxidation of these metabolites leads to the
      electrophilic quinones, which are presumably involved in the tumor-initiating
      process. A synthetic route based on the McMurry coupling reaction was developed
      for the synthesis of 3'-OH-DES. Using commercially inexpensive starting
      materials, this compound was synthesized in four steps, and the cis and trans
      isomers were separated and identified. Following the same synthetic route, 3'-OH
      HES was synthesized in five steps.

PMID- 9585471
TI  - Metabolic activation and formation of DNA adducts of hexestrol, a synthetic
      nonsteroidal carcinogenic estrogen.
AB  - Hexestrol (HES), a synthetic nonsteroidal estrogen, is carcinogenic in Syrian
      golden hamsters. The major metabolite of HES is its catechol, 3'-OH-HES, which
      can be metabolically converted to the electrophilic catechol quinone, HES-3',4'
      Q, by peroxidases and cytochrome P450. Standard adducts were synthesized by
      reacting HES-3',4'-Q with dG and dA to produce the adducts 3'-OH-HES-6'(alpha,
      beta)-N7Gua and HES-3',4'-Q-6'-N6dA, respectively. When HES-3',4'-Q was reacted
      with calf thymus DNA, 3'-OH-HES-6'(alpha,beta)-N7Gua was identified by HPLC and
      tandem mass spectrometry as the depurinating adduct, with minor amounts of stable
      adducts. 3'-OH-HES was bound to DNA after activation by horseradish peroxidase,
      lactoperoxidase, or rat liver microsomes. The depurinating adduct 3'-OH-HES
      6'(alpha, beta)-N7Gua was identified in these systems at levels of 65, 41, and 11
      micromol/mol of DNA-P, respectively. Unidentified stable adducts were observed in
      much lower amounts and were quantified by the 32P-postlabeling method. Similarly
      to 3'-OH-HES, the catechol metabolites of the natural steroidal estrogens estrone
      (E1) and estradiol (E2), namely, 2-OHE1, 4-OHE1, 2-OHE2, and 4-OHE2, can be
      oxidized to their corresponding quinones by peroxidases and cytochrome P450. The
      quinones of the carcinogenic 4-OHE1 and 4-OHE2 have chemical and biochemical
      properties similar to those of HES-3',4'-Q. The results suggest that formation of
      HES-3',4'-Q may be a critical event in tumor initiation by HES and that HES is an
      excellent model compound to corroborate the hypothesis that estrogen-3,4-quinones
      are ultimate carcinogenic metabolites of the natural steroidal estrogens E1 and
      E2.

PMID- 9585472
TI  - Comparison of the formation of 8-hydroxy-2'-deoxyguanosine and single- and double
      strand breaks in DNA mediated by fenton reactions.
AB  - The formation of 8-hydroxydeoxyguanosine (8-OHdG) and both single- and double
      strand breaks in DNA by Fenton-type reactions has been investigated. Salmon sperm
      DNA was exposed to hydrogen peroxide (50 mM) and one of nine different transition
      metal ions (25 microM-1 mM). Modified DNA was isolated and subjected to analysis
      by liquid chromatography coupled to an electrochemical detection system (LC-ECD),
      to evaluate the formation of 8-OHdG. The highest yield of 8-OHdG was obtained
      following treatment of DNA with the chromium(III) Fenton reaction (a maximum of
      19 400/10(6) nucleotides), followed by iron(II) (13 600), vanadium(III) (5800),
      and copper(II) (5200). The chromium(VI) Fenton reaction generated a moderate
      yield of 8-OHdG (3600/10(6) nucleotides), while the yield obtained in DNA treated
      with cobalt(II), nickel(II), cadmium(II), and zinc Fenton reactions was not
      significantly higher than in control incubations of DNA with hydrogen peroxide
      alone. Similar treatment of the double-stranded plasmid pBluescript K+ with
      hydrogen peroxide (1 mM) and each transition-metal ion (1-100 microM) followed by
      quantitative agarose gel electrophoresis demonstrated that open-circle DNA,
      resulting from single-strand breaks, was generated in Fenton reactions involving
      all nine metal ions. In contrast, linear DNA was only formed in Fenton reactions
      involving chromium(III), copper(II), iron(II), and vanadium(III) ions. Formation
      of linear DNA, under conditions that generated relatively few single-strand
      breaks, suggests that these four transition-metal ions partake in Fenton
      reactions to generate true double-strand breaks. Furthermore, the generation of 8
      OHdG exhibits a good correlation with the formation of double-strand breaks,
      suggesting that they arise by a similar mechanism.

PMID- 9585473
TI  - Effects of peroxisome proliferators on rat liver phospholipids: sphingomyelin
      degradation may be involved in hepatotoxic mechanism of perfluorodecanoic acid.
AB  - Perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), clofibrate, di(2
      ethylhexyl)phthalate (DEHP), and Wy-14,643 represent a class of compounds known
      as peroxisome proliferators (PPs). Such compounds induce biogenesis of liver
      peroxisomes and cause a varying degree of hepatotoxicity and carcinogenesis in
      rodents. We examined the effects of these PPs on rat hepatic lipids and
      phospholipid profiles using phosphorus-31 NMR spectroscopy. All PPs caused a 25
      57% increase in hepatic phospholipid content, while all but clofibrate increased
      the total lipid content by 26-156%. Treatments also influenced the composition of
      liver phospholipids. Phosphatidylcholine (PtdCho) and phosphatidylethanolamine
      (PtdEth) contents were significantly increased in all treatment groups. Most
      notably, PFDA caused the largest increase in PtdCho and PtdEth content (ca. 70%),
      while PFOA and Wy-14,643 were the only test compounds that influenced the
      PtdCho:PtdEth ratio. PFDA also caused an ca. 30% decrease in sphingomyelin (SphM)
      from 24 to 120 h postdose. SphM is a key lipid in signal transduction processes
      involved in apoptosis. Hydrolysis of SphM can be mediated through the action of
      tumor necrosis factor (TNF-alpha). We measured the TNF-alpha concentrations in
      rat sera at 24 h post-PFDA-exposure and found an 8-fold increase relative to
      vehicle-treated controls. These data demonstrate that an increase in the serum
      TNF-alpha level correlates with the time frame for the observed reduction in
      hepatic SphM. PFOA, a structurally similar compound, had no effect on hepatic
      SphM content, nor did it affect the serum TNF-alpha concentration. These effects
      may be related to differences in the tumorigenicity associated with these
      compounds. We postulate that PFDA activates the SphM signal transduction pathway
      via the release of TNF-alpha. This then stimulates cytotoxic responses and
      processes of apoptosis and may suppress cell proliferative and mitogenic
      responses.

PMID- 9585474
TI  - Fractionation of aqueous cigarette tar extracts: fractions that contain the tar
      radical cause DNA damage.
AB  - Previously, we have shown that aqueous cigarette tar (ACT) extracts contain a
      long-lived tar radical that associates with DNA in isolated rat alveolar
      macrophages and causes DNA damage in isolated rat thymocytes. These ACT solutions
      reduce oxygen to produce superoxide and, ultimately, hydrogen peroxide. In this
      study, we report the fractionation of ACT solutions prepared from the tar from
      five cigarettes using Sephadex columns. The fractions were analyzed by UV and
      electron paramagnetic resonance (EPR) spectroscopy and gas chromatography/mass
      spectrometry (GC/MS). The fractions containing polyphenolic species (principally
      catechol and hydroquinone, as determined by MS) caused most of the observed DNA
      damage in rat thymocytes. These DNA-damaging fractions produced superoxide, H2O2,
      and hydroxyl radicals. Stable free radicals were identified as o- and p
      benzosemiquinone radicals by EPR spectroscopy. Hydroxyl radicals were detected by
      EPR spin-trapping with 5, 5-dimethyl-1-pyrroline N-oxide (DMPO). Catalase
      inhibited the EPR signal of the DMPO-OH adduct, indicating that H2O2 is the
      precursor of the hydroxyl radical spin adduct. The Sephadex separation resulted
      in a 90-fold concentration of the hydrogen peroxide-generating capacity of the
      fractions that contained polyphenols, relative to the unfractionated ACT
      solution. Another fraction, which contained nicotine, caused some DNA damage, but
      this damage was 28-fold less than the damage caused by the most damaging phenolic
      fraction. These results support our hypothesis that the tar radical system is an
      equilibrium mixture of semiquinones, hydroquinones, and quinones. The tar radical
      associates with DNA, causes DNA damage, and very likely is involved in the
      toxicity associated with cigarette smoking.

PMID- 9585476
TI  - Reactivity of haloketenes and halothioketenes with nucleobases: chemical
      characterization of reaction products.
AB  - Halothioketenes and haloketenes are postulated as intermediates in haloolefin
      bioactivation. Little is known about the interactions of these reactive
      intermediates with macromolecules such as DNA. DNA binding, however, may be
      relevant in the toxicity of the parent olefins since they or their proximate
      metabolites are genotoxic. This prompted us to elucidate the structures and
      properties of potential DNA adducts formed. Adenine, cytosine, guanine, and
      thymine were reacted with chloro- and dichlorothioketene, chloro- and
      dichloroketene, and chloro- and dichloroacyl chloride. While thymine did not
      react, adenine and cytosine formed stable DNA base adducts with all reaction
      partners as demonstrated by HPLC analysis. Guanine yielded only products with
      chloroketene and chloroacetyl chloride. The pH-dependent UV spectra, 1H and 13C
      NMR, FT-IR, and elemental analysis showed (i) nucleophilic attack of the
      exocyclic amino groups of the DNA bases yielded haloacyl (thio)amides with all
      reactants as clearly demonstrated by the FT-IR spectra; (ii) the sulfur in the
      initial thioamides seems to be rapidly exchanged with oxygen; (iii) the acyl
      chlorides form identical products but in lower yields as compared to the
      haloketenes. Reactions of the nucleosides with haloketenes showed the formation
      of similar nucleoside adducts upon HPLC and MS analysis. Beside the modification
      of the base moieties, additional peaks in the reaction mixtures analyzed
      suggested acylation of the deoxyribose hydroxyl groups. In aqueous solutions at
      pH 7 N6-(chloroacetyl)adenine, N4-(chloroacetyl)cytosine, and N2
      (chloroacetyl)guanine are not stable and cleaved to the original base or form
      1,N6-acetyladenine, 3,N4-acetylcytosine, 1,N2-acetylguanine, and N2,3
      acetylguanine. Under the same conditions, N6-(dichloroacetyl)adenine and N4
      (dichloroacetyl)cytosine were completely hydrolyzed to adenine and cytosine,
      respectively. All haloacyl DNA base adducts proved to be stable at pH 5 but were
      rapidly degraded at neutral or alkaline pH. The compounds with an additional five
      membered ring remained unchanged after 1 week at room temperature. All
      synthesized DNA base adducts except N2-(chloroacetyl)guanine and 1,N2
      acetylguanine were fluorescent. The characterized compounds, especially the
      etheno (epsilon) base adduct-related derivatives, may represent potential DNA
      adducts formed as a consequence of haloolefin bioactivation.

PMID- 9585475
TI  - Oxidative transformations of 1-nitropyrene under simulated environmental
      conditions.
AB  - The oxidation of 1-nitropyrene (1-NP), adsorbed on silica gel, with
      dimethyldioxirane (DMD) leads to the formation of 1-nitropyrene 4,5-oxide and 1
      nitropyrene 9,10-oxide in a ratio of 74/26 (4,5-oxide/9,10-oxide). When the
      adsorbed 1-NP is exposed to the products of the gas-phase reaction of
      tetramethylethylene (TME) with ozone at -40 degrees C, the same oxides are
      produced in a ratio of 72/28. The fact that the ratio of the oxides is
      essentially the same in these two different types of experiments is highly
      significant. We have speculated that the gas-phase ozonolysis of TME produces an
      energy-rich form of the carbonyl oxide, acetone oxide. Some of this carbonyl
      oxide may cyclize to the isomeric DMD which, we propose, is responsible for oxide
      formation in the TME/ozone experiment. This proposal is supported by the
      observation that using ozone alone to oxidize 1-NP does not lead to oxide
      formation. Thus the oxidant responsible for oxide formation in the TME/ozone
      experiment must be produced in the ozonolysis. We suggest that this oxidant is
      DMD.

PMID- 9585477
TI  - Reactivity of haloketenes and halothioketenes with nucleobases: reactions in
      vitro with DNA.
AB  - Ketenes are important and highly reactive intermediates. Thioketenes are formed
      by cysteine conjugate beta-lyase-dependent biotransformation of 1
      halovinylcysteine S-conjugates which are metabolites of several halogenated
      olefins. Nucleic acid constituents react with haloketenes and halothioketenes in
      vitro. Thioketenes induce DNA strand breaks in incubations of 1,2-dichlorovinyl 2
      nitrophenyl disulfide, a thioketene precursor, with pBr 322 plasmid DNA. After
      treatment of single-stranded or native calf thymus DNA with chlorothioketene
      generated by the hydrolysis of 1,2-dichlorovinyl 2-nitrophenyl disulfide, the
      formation of 3,N4-thioacetylcytosine could be demonstrated. N6
      (Dichloroacetyl)adenine and N4-(dichloroacetyl)cytosine, however, adducts formed
      by dichloroketene in vitro, are labile to hydrolysis. Therefore, the binding of
      this compound to DNA constituents in intact DNA is difficult to demonstrate.
      Substitution of one chlorine atom by fluorine allowed us to use 19F NMR as a tool
      to demonstrate the formation of adducts by dihaloketenes in intact DNA. N6
      (Chlorofluoroacetyl)adenine and N4-(chlorofluoroacetyl)cytosine were synthesized
      (yields 77%, 15%, respectively) as references and characterized by LC/MS, 1H,
      13C, and 19F NMR, FT-IR, and elemental analysis. To demonstrate the ability of
      dihaloketenes to bind to DNA, poly-dA (1 mg) and calf thymus DNA (10 mg) were
      suspended in DMF and treated with different concentrations of chlorofluoroketene
      (50-200 micromol). Analysis of the polymeric DNA by 19F NMR showed one doublet at
      -137.2 ppm downfield from the reference (CFCl3). A doublet at -146.9 ppm,
      characteristic for chlorofluoroacetic acid, an expected product of DNA adduct
      hydrolysis, was not detected. These results demonstrate the formation of a stable
      adenine adduct by dihaloketenes in intact calf thymus DNA.

PMID- 9585478
TI  - Hemoglobin binding of bicyclic aromatic amines.
AB  - Aromatic diamino compounds, e.g., 4,4'-methylenebis(2-chloroaniline) (MOCA) and
      4,4'-methylenedianiline (MDA), are used as curing agents in the production of
      elastomers. Since MOCA and MDA are mutagenic and carcinogenic, substitutes are of
      great commercial interest. For benzidine it has been shown that ortho
      substitution with methyl groups yields the nonmutagenic 3,3',5,5'
      tetramethylbenzidine. Therefore, MDA analogues with large substituents in the
      ortho position have been synthesized. The substituents are supposed to inhibit
      the formation of the N-hydroxyarylamines which are the putative genotoxic
      intermediates. We investigated the biological availability of the N
      hydroxylamines of ortho-substituted diamines and of known carcinogenic diamines
      in female Wistar rats, by determining hemoglobin (Hb) adducts. Hb from rats dosed
      with 0.5 mmol/kg diamine and from controls was isolated and hydrolyzed in base.
      The released diamine and monoacetyldiamine were quantified by HPLC with
      electrochemical detection and/or GC/MS. MDA, 4,4'-oxydianiline (ODA), 4,4'
      ethylenedianiline, and 4,4'-thiodianiline (TDA) bound to hemoglobin as diamine
      and as monoacetyl-diamine. 4,4'-Methylenebis(2,6-dimethylaniline), 4,4'
      methylenebis(2,6-diethylaniline), MOCA, and 4,4'-sulfonyldianiline (dapsone)
      bound only as diamine to Hb. 4,4'-Methylenebis(2,6-dichloroaniline) did not bind
      to Hb. Thus, the presence of two substituents in the ortho position and the
      presence of electron-withdrawing groups in the para position to the amino group
      drastically reduced the formation of Hb adducts. The amount of hemoglobin adducts
      was compared to their carcinogenic potency. The extent of hemoglobin binding of
      the bicyclic diamines (dapsone, 3,3'-dichlorobenzidine, MDA, MOCA, TDA, ODA, and
      benzidine) increases with their carcinogenic potency.

PMID- 9585479
TI  - Oxidation and antioxidation of human low-density lipoprotein and plasma exposed
      to 3-morpholinosydnonimine and reagent peroxynitrite.
AB  - As peroxynitrite is implicated as an oxidant for low-density lipoprotein (LDL) in
      atherogenesis, we investigated this process using reagent peroxynitrite (ONOO-)
      and 3-morpholinosydnonimine (SIN-1, which produces peroxynitrite via generation
      of NO. and O2.-). LDL oxidation was assessed by the consumption of ubiquinol-10
      (CoQ10H2) and alpha-tocopherol (alpha-TOH), the accumulation of cholesteryl ester
      hydro(pero)xides, the loss of lysine (Lys) and tryptophan (Trp) residues, and the
      change in relative electrophoretic mobility. Exposure to ONOO- or SIN-1 resulted
      in rapid (<1 min) and time-dependent oxidation, respectively, of LDL's lipids and
      protein. Manipulating the alpha-TOH content by in vivo or in vitro means showed
      that when ONOO- or SIN-1 was used at oxidant-to-LDL ratios of <100:1 the extent
      of LDL lipid peroxidation increased with increasing initial alpha-TOH content. In
      contrast, in vivo enrichment with the co-antioxidant CoQ10H2 decreased LDL lipid
      peroxidation induced by SIN-1. At oxidant-to-LDL ratios of >200:1, alpha-TOH
      enrichment decreased LDL lipid peroxidation for both SIN-1 and ONOO-. In contrast
      to lipid peroxidation, altering the alpha-TOH content of LDL did not affect Trp
      or Lys loss, independent of the amounts of either oxidant added. Aqueous
      antioxidants inhibited ONOO--induced lipid and protein oxidation with the order
      of efficacy: 3-hydroxyanthranilate (3-HAA) > urate > ascorbate. With SIN-1, these
      antioxidants inhibited Trp consumption, while only the co-antioxidants ascorbate
      and 3-HAA prevented alpha-TOH consumption and lipid peroxidation. Exposure of
      human plasma to SIN-1 resulted in the loss of ascorbate followed by loss of
      CoQ10H2 and bilirubin. Lipid peroxidation was inhibited during this period,
      though proceeded as a radical-chain process after depletion of these antioxidants
      and in the presence of alpha-TOH and urate. Bicarbonate at physiological
      concentrations decreased ONOO--induced lipid and protein oxidation, whereas it
      enhanced SIN-1-induced lipid peroxidation, Trp consumption, and alpha
      tocopheroxyl radical formation in LDL. These results indicate an important role
      for tocopherol-mediated peroxidation and co-antioxidation in peroxynitrite
      induced lipoprotein lipid peroxidation, especially when peroxynitrite is formed
      time-dependently by SIN-1. The studies also highlight differences between ONOO--
      and SIN-1-induced LDL oxidation with regards to the effects of bicarbonate,
      ascorbate, and urate.

PMID- 9585480
TI  - Enzymatic reduction of 3-nitrotyrosine generates superoxide.
AB  - Spin-trapping with 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) was used to
      demonstrate that 3-nitrotyrosine (nitrotyrosine) promotes the formation of
      substantial amounts of reactive oxygen species (O2.- and *OH), when incubated
      with NAD(H)-cytochrome c reductase and a corresponding electron donor. Spin
      adduct formation is strongly inhibited by the presence of superoxide dismutase
      (SOD); spin adduct formation requires aerobic conditions. Nitration of leucine
      enkephalin, a tyrosine-containing pentapeptide, results in a similar generation
      of O2*- and *OH species. Both nitrotyrosine and nitrated leucine enkephalin
      stimulate acetylated ferricytochrome c reduction in the presence of NAD(H)
      cytochrome c reductase with typical Michaelis-Menten kinetics and Km's of 104 +/-
      14 and 0.78 +/- 0.11 microM, respectively. No stimulation of acetylated
      ferricytochrome c reduction is observed in the presence of SOD. Catalase and the
      metal chelators DTPA and deferoxamine mesylate do not influence observed
      stimulation of acetylated ferricytochrome c reduction by nitrotyrosine. Nitration
      of two tyrosines (of four) within the sequence of the 6.5-kDa globular protein
      bovine pancreas trypsin inhibitor (BPTI) fails to stimulate O2*- generation
      implying steric restrictions for BPTI-reductase interactions. However, nitrated
      BPTI subjected to trypsin digestion stimulated reduction of acetylated
      ferricytochrome c. These results suggest that, as with other nitroaromatic
      compounds, nitrotyrosine may be enzymatically reduced to the corresponding nitro
      anion radical (ArNO2*-) which is then oxidized by molecular oxygen to yield O2*-
      and regenerate ArNO2. Thus, once formed in vivo, nitrotyrosine may act to promote
      oxidative stress by means of repetitive redox cycling.

PMID- 9585481
TI  - Occurrence of the NIH shift upon the cytochrome P450-catalyzed in vivo and in
      vitro aromatic ring hydroxylation of fluorobenzenes.
AB  - The in vivo cytochrome P450-catalyzed aromatic hydroxylation of a series of
      fluorobenzenes was investigated with special emphasis on the importance of the
      fluorine NIH shift. The results obtained demonstrate a minor role for the NIH
      shift in the metabolism of the fluorobenzenes to phenolic metabolites in control
      male Wistar rats. These in vivo results could indicate that (1) the NIH shift is
      an inherently minor process for fluorine substituents or (2) it is a potentially
      significant process but the presumed epoxide that leads to formation of the NIH
      shifted metabolite is lost to an alternative metabolic pathway. In contrast to
      the in vivo data, in vitro experiments showed a significant amount of an NIH
      shifted metabolite for 1,4-difluorobenzene. This result eliminates the
      explanation that the NIH shift is an inherently minor process for fluorine
      substituents. Results of additional experiments presented in this paper show that
      the reduced tendency of fluorine-substituted benzenes to undergo an NIH shift in
      vivo can-at least in part-be ascribed to the possible existence of alternative
      pathways for metabolism of the epoxide, such as, for example, GSH conjugation,
      being more efficient for fluorinated than chlorinated arene oxides.

PMID- 9585482
TI  - Selective protein adduct formation of diclofenac glucuronide is critically
      dependent on the rat canalicular conjugate export pump (Mrp2).
AB  - Previous work demonstrates that the reactive acyl glucuronide of the nonsteroidal
      antiinflammatory drug diclofenac forms selective protein adducts in the liver,
      which may play a causal role in the pathogenesis of diclofenac-associated liver
      toxicity. Because glucuronide conjugates can be exported into the bile, we
      explored the role of diclofenac glucuronide hepatobiliary transport in the
      formation of site-specific protein adducts. Specifically, to analyze
      intracellular (hepatocytes) versus extracellular (biliary tree) targeting of
      proteins, we have compared the pattern of diclofenac binding in normal Wistar
      rats with that in mutant transport-deficient (TR-) rats which lack the functional
      canalicular isoform of the conjugate export pump, Mrp2. In bile duct-cannulated
      normal rats, >50% of an iv injected dose of [14C]diclofenac appeared in the bile
      over a 90-min period. In contrast, in TR- rats virtually no hepatobiliary
      excretion of diclofenac glucuronide was found. After administration of diclofenac
      (30 mg/kg/day, ip for 3 days) to rats of both genotypes, a major protein adduct
      of an apparent molecular mass of 118 kDa was selectively detected by
      immunoblotting in isolated canalicular, but not in basolateral, membrane
      subfractions of wild-type rats, whereas no plasma membrane adducts could be found
      in the livers of TR- rats. Furthermore, immunohistochemical analysis using an
      anti-diclofenac antibody revealed the presence of distinct diclofenac-modified
      proteins on canalicular membranes of liver sections from diclofenac-treated
      normal rats, whereas no adducts could be identified in livers of TR- rats. In
      Western blots, the major diclofenac-modified canalicular membrane protein did not
      comigrate with Mrp2, indicating that the glucuronide carrier itself was unlikely
      to be a target. Collectively, the results demonstrate that the reactive
      diclofenac glucuronide is selectively transported into bile via Mrp2 and that
      hepatobiliary transport is critical for diclofenac covalent binding to proteins
      in the biliary tree.

PMID- 9585483
TI  - Application of gas chromatography/electron capture negative chemical ionization
      high-resolution mass spectrometry for analysis of DNA and protein adducts.
AB  - The analytical potential of gas chromatography/electron capture negative chemical
      ionization high-resolution mass spectrometry (HRMS) for characterization and
      quantitation of DNA and hemoglobin adducts was demonstrated using three model
      compounds: N2, 3-ethenoguanine (EG), 7-(2-hydroxyethyl)guanine (7-HEG), and N-(2
      hydroxyethyl)valine (HEV). At a resolving power of 10 000, the signal-to-noise
      (S/N) ratios obtained from quantitative selected ion monitoring (SIM) experiments
      using biological samples were comparable to or better than existing unit mass
      resolution experiments due to the reduction of chemical noise from the use of
      narrower mass windows. The specificity gained by HRMS was essential for
      quantitation of ultratrace amounts near the limit of detection since coeluting
      interferences of the analyte or internal standard can lead to inaccurate
      measurement of response factors. The limit of detection (LOD) was 100 amol (S/N =
      5) using a pure standard of TTB2-EG. The LOD for complete assays using spiked
      samples was 500 amol (S/N = 5) for EG and 600 amol (S/N = 5) injected for 7-HEG.
      The standard deviation (SD) for the HRMS quantitative measurements was typically
      less than 10%. The SD for the complete biological assays as determined by spiking
      replicate samples was less than 15%. This method has adequate sensitivity and
      specificity to accurately measure DNA and protein adducts as low as endogenous
      concentrations in rodent and human tissues.

PMID- 9585484
TI  - Determination of DNA damage in F344 rats induced by geometric isomers of
      tamoxifen and analogues.
AB  - To investigate the activation mechanisms involved in tamoxifen carcinogenicity,
      analogues of tamoxifen isomers modified at the ethyl group were synthesized and
      assessed for their ability to induce hepatic DNA damage following their
      administration to female F344 rats. The cis isomer was prepared by acid-catalyzed
      isomerization of tamoxifen and isolated by preparative HPLC. The active
      metabolite alpha-hydroxytamoxifen and geometric isomers of bromotamoxifen and C
      desmethylenetamoxifen, analogues in which the ethyl group has been replaced by a
      bromine atom and methyl group, respectively, were synthesized according to
      published procedures. The levels of hepatic DNA adducts induced were determined
      by 32P-postlabeling. Bromotamoxifen and tamoxifen 1,2-epoxide caused no
      detectable DNA damage relative to controls. Trans isomers of tamoxifen, C
      desmethylenetamoxifen, and alpha-hydroxytamoxifen all produced DNA adducts at a 5
      90-fold higher level than the corresponding cis isomers. In contrast, both the
      cis and trans isomers of alpha-hydroxytamoxifen showed similar reactivity toward
      calf thymus DNA in vitro. Molecular models of alpha-hydroxytamoxifen isomers
      suggest this difference in DNA adduct-forming ability is due to steric hindrance
      of the enzymes involved in the activation of this metabolite. There were high
      adduct levels in the liver, but no uterine DNA adducts were detected in rats
      treated with alpha-hydroxytamoxifen. This suggests that in contrast to the liver,
      alpha-hydroxytamoxifen is not further activated in rat uterus. This may help to
      explain the absence of uterine tumors in rats following long-term tamoxifen
      treatment.

PMID- 9585485
TI  - Mechanism for benomyl action as a mitochondrial aldehyde dehydrogenase inhibitor
      in mice.
AB  - Benomyl (a non-thio fungicide) inhibits hepatic mitochondrial low-Km aldehyde
      dehydrogenase (mALDH or ALDH2) in ip-treated mice by 50% (IC50) at 7.0 mg/kg,
      which is surprisingly the same potency range as that for several dithiocarbamate
      fungicides (and the related alcohol abuse drug disulfiram) and thiocarbamate
      herbicides previously known for their alcohol-sensitizing action. The mechanism
      by which benomyl inhibits mALDH was therefore examined, first by comparing the
      metabolism of benomyl with the aforementioned mono- and dithiocarbamates and
      second by evaluating the inhibitory potency of the benomyl metabolites. Benomyl
      in ip-treated mice is converted, via butyl isocyanate, S-(N
      butylcarbamoyl)glutathione, and S-(N-butylcarbamoyl)cysteine, to S-methyl N
      butylthiocarbamate (MBT), identified as a transient metabolite in liver. MBT is
      >10-fold more potent than benomyl or butyl isocyanate as an in vivo mALDH
      inhibitor and is also more potent than the intermediary S-(N-butylcarbamoyl)
      conjugates. Benomyl and MBT inhibit mouse hepatic mALDH in vitro with IC50s of
      0.77 and 8.7 microM, respectively. The potency of MBT is greatly enhanced by
      fortification of the mitochondria with NADPH alone or plus microsomes giving
      IC50s of 0.50 and 0.23 microM, respectively. This activation of MBT is almost
      completely blocked by the cytochrome P450 inhibitor N-benzylimidazole but not by
      several other cytochrome P450 inactivators. MBT (probably following
      bioactivation) inhibits mALDH in vivo with an IC50 of 0.3 mg/kg. Two candidate
      activation products were synthesized for potency determinations. N-Hydroxy MBT
      (prepared via the trimethylsilyl derivative) was not detected as an MBT
      metabolite; its low potency also rules against N-hydroxylation as the activation
      process. MBT sulfoxide, from oxidation of MBT with magnesium monoperoxyphthalate
      in water, is one of the most potent inhibitors known for mALDH and yeast ALDH in
      vitro (IC50 0.08-0.09 microM). These findings are consistent with a six-step
      bioactivation of benomyl, via the metabolites above and N-butylthiocarbamic acid,
      with MBT as the penultimate and MBT sulfoxide as the ultimate inhibitor of mALDH.

PMID- 9585486
TI  - Carbon disulfide and N,N-diethyldithiocarbamate generate thiourea cross-links on
      erythrocyte spectrin in vivo.
AB  - CS2, a known neurotoxicant, is used in the viscose production of rayon and is
      also a decomposition product of N, N-diethyldithiocarbamate, a metabolic product
      of the drug disulfiram used in alcohol aversion therapy. Previous in vitro
      investigations have demonstrated the ability of CS2 to cross-link proteins
      through thiourea, dithiocarbamate ester, and disulfide structures. Although in
      vivo studies have supported protein cross-linking as both a mechanism of
      neurotoxicity and a potential biomarker of effect, the chemical structures
      responsible for CS2-mediated protein cross-linking in vivo have not been
      elucidated. In the present study, the structure of one type of stable protein
      cross-link produced on erythrocyte spectrin by CS2 in vivo is determined. Rats
      were exposed to 50, 500, and 800 ppm CS2 for 13 weeks by inhalation or to 3
      mmol/kg N,N-diethyldithiocarbamate administered orally on alternating days for 8
      weeks. Erythrocyte spectrin preparations from control and exposed rats were
      hydrolyzed using 6 N HCl and separated by size-exclusion chromatography. The
      fraction that coeluted with the synthetic deuterated lysine-lysine thiourea
      internal standard was derivatized with 3-[4'-[(N,N,N
      trimethylamino)ethylene]phenyl] 2-isothiocyanate and analyzed by liquid
      chromatography tandem mass spectrometry using selected reaction monitoring
      detection. Lysine-lysine thiourea was detected in spectrin preparations obtained
      from CS2-treated rats at 500 and 800 ppm and N, N-diethyldithiocarbamate-treated
      rats, but not from controls. These results establish that CS2-mediated protein
      cross-linking occurs in vivo through the generation of Lys-Lys thiourea and that
      diethyldithiocarbamate can, through in vivo release of CS2, produce the same
      cross-linking structure. This observation supports the utility of cross-linking
      of peripheral proteins as a specific dosimeter of internal exposure for CS2 and
      provides a mechanistic explanation to account for the high-molecular-weight
      neurofilament protein species isolated from rats exposed to CS2 or N, N
      diethyldithiocarbamate.

PMID- 9585487
TI  - Mutations induced in the supF gene of pSP189 by hydroxyl radical and singlet
      oxygen: relevance to peroxynitrite mutagenesis.
AB  - We previously showed that the oxidant peroxynitrite (ONOO-) was strongly
      mutagenic in the supF shuttle vector pSP189 replicated in bacteria or human
      cells. Qualitative characteristics of the mutational spectra induced by ONOO-
      differed significantly from those reportedly caused by hydroxyl radical (OH.) in
      other experimental systems but showed similarities to spectra reportedly produced
      by singlet oxygen (1O2). The molecular mechanisms of ONOO--mediated DNA damage
      are unknown. The objective of the present set of experiments was to characterize
      mutational effects induced in the supF gene of pSP189 by OH* and 1O2 to permit
      direct comparison with mutational spectra induced by ONOO- in this system. Base
      substitutions were the major form of mutation induced in plasmids replicated in
      human (AD293) cells by ONOO- (84%) and 1O2 (71%), whereas OH* induced fewer of
      them (49%). In plasmids replicated in bacteria (Escherichia coli MBL50),
      frequencies of base substitutions induced by the three treatments were similar.
      G:C-to-T:A transversions were the most common form of base substitution induced
      by ONOO- (75% and 67%, respectively, in AD293- and MBL50-replicated plasmids) and
      1O2 (68% and 71%); they were induced at lower frequencies by OH. (51% and 47%).
      G:C-to-C:G transversions or G:C-to-A:T transitions were induced at almost equal
      frequencies by both ONOO- and 1O2, whereas OH* induced these mutations at
      different frequencies in the AD293 system. Collectively, our results confirm that
      in several important respects mutational spectra induced by ONOO- have greater
      similarity to spectra induced by 1O2 than to those induced by OH* and suggest
      that genotoxic derivatives of ONOO- are likely to include species that have DNA
      damaging properties resembling those of 1O2 in selectivity for guanine but not
      identical in sequence specificity.

PMID- 9585489
TI  - Call for Papers: Peer-led Interventions
AB  - Copyright 1998 The Association for Professionals in Services for
      AdolescentsCopyright 1998 The Association for Professionals in Services for
      Adolescents.

PMID- 9585488
TI  - Formation and properties of peroxynitrite as studied by laser flash photolysis,
      high-pressure stopped-flow technique, and pulse radiolysis volume 10, number 11,
      november 1997, pp 1285-1292 

PMID- 9585490
TI  - Call for Papers: Adolescent Tobacco Use
AB  - Copyright 1998 The Association for Professionals in Services for
      AdolescentsCopyright 1998 The Association for Professionals in Services for
      Adolescents.

PMID- 9585491
TI  - Psychosocial correlates of adolescent drug-taking behavior.
AB  - This research was designed to test the extent to which personality, environmental
      factors, and conventional behaviours predict drug-taking among a sample of
      Australian high school students. Respondents (n = 199; 101 females and 98 males)
      indicated the extent of their alcohol, tobacco and marijuana use. Correlational
      analyses showed broad support for the view that personality and environmental
      factors as well as conventional behaviours are related to drug use. Regression
      analyses showed that the significant predictors of drug use vary according to the
      drug in question. In particular, the predictors of mood-enhancing drugs (alcohol
      and marijuana) appear distinctive from the predictors of tobacco use. The results
      are discussed in the context of previous research in this area.

PMID- 9585492
TI  - Addiction-risk behaviours and suicide attempts in adolescents.
AB  - Data on single and multiple addiction-risk behaviours and suicidal behaviour were
      obtained from a large sample of Dutch secondary school students aged 16 to 19
      years. Although the prevalence of hard drugs was the lowest of all addiction-risk
      behaviours, there was a markedly high report of suicidal behaviours in youngsters
      who used these drugs: one out of each five boys and one out of each three girls.
      The most "suicidal" combination of two addiction-risk behaviours reported by
      girls was that of sedatives and hard drugs: more than half of the girls who
      reported both these behaviours also reported a suicide attempt. In boys, 27% of
      those who reported sedatives and cigarettes also reported a suicide attempt. The
      number of addiction-risk behaviours reported by the adolescents showed an almost
      linear increasing relation with the percentage of suicide attempters. The results
      suggest that suicidal behaviour and addiction-risk behaviours both should be
      regarded as part of a complex interaction of multiple behavioural problems.
      Prevention programmes and intervention strategies should focus on multiple rather
      than single targets, and screening procedures to detect adolescents at-risk for
      suicidal behaviour should focus on patterns of multiple risk factors rather than
      on single behaviours.

PMID- 9585493
TI  - Risk-taking patterns of female adolescents: what they do and why.
AB  - A total of 58 college-age adolescent females were asked to provide information
      about their risk-taking behaviors. Participants completed a risk-taking
      questionnaire and were asked to keep a diary of their risk-taking behaviors for 1
      week. Participants were also asked to provide reasons for engaging in each
      behavior they listed. Results indicated that participants engaged in a variety of
      risky behaviors ranging from traditional adolescent risk-taking behaviors, e.g.
      drinking and sex, to other behaviors not typically included in studies of risk
      taking, e.g. interpersonal and financial risky behaviors. An analysis of the
      justifications given for engaging in the various behaviors were largely goal
      oriented (e.g. engaging in a behavior as a means to an end) or reflected a
      preoccupation with personal needs (e.g. engaging in a behavior to relieve
      loneliness or stress). These results are contrary to the widely held belief that
      adolescents' risk-taking is "mindless," "aimless," or mere "sensation seeking."

PMID- 9585494
TI  - The quality of perceived parenting experienced by a group of Scottish
      incarcerated young offenders and its relation to psychological distress.
AB  - This study utilized the Parental Bonding Instrument [PBI] in a group of 125
      incarcerated Scottish young offenders aged 16-21. The study examined the response
      profiles of young offenders and compared the results to normative data and
      demographics relating to family and penal experiences. Furthermore, it
      investigated relationships between parenting style and levels of depression,
      anxiety and hopelessness experienced during incarceration. Significant
      differences between the current sample and the normative sample were found.
      Stepwise regression analyses highlighted the role that parental overprotection
      plays in any psychological distress experienced during incarceration. The study
      also considered parental style and discusses the place of Parker's "optimal
      parenting" style in this particular population. The practical ramifications of
      these findings are also discussed in relation to the effects that current
      perceptions of the parenting role has upon the individual's own parenting
      behaviour.

PMID- 9585495
TI  - Exploring teenagers' accounts of bad communication: a new basis for intervention.
AB  - Interventions to enhance young people's communication are rarely based on
      research into adolescent communication, but take a more general, analytic, skills
      based approach. This paper argues that evidence of young people's communication
      experiences is an important resource to inform the targeting and content of
      interventions, which has hitherto been overlooked. An exploratory, hypothesis
      generating study of teenagers' accounts of their communication experiences was
      carried out. Four thousand and forty-eight adolescents aged 13-19 described a
      recent communication experience with (i) a family member, (ii) a friend or (iii)
      a non-family adult (professional or official). Self-reported bad communication
      experiences outweighted good ones only in adolescents' communications with adults
      outside the family, and there were significant variations across contexts in
      terms of the purposes, explanations and attributions for perceived bad
      communication. Implications of the research for future interventions are
      discussed.

PMID- 9585496
TI  - Adolescent gender differences in HIV-related sexual risk acts, social-cognitive
      factors and behavioral skills.
AB  - Variations in perceived HIV risk, peer and partner social norms regarding safe
      sex, self-efficacy, outcome expectancies, and risk-reduction skills (condom use
      competence and safe sex negotiation) based on gender and sexual risk level were
      assessed among 132 heterosexual, sexually active, inner city adolescents. Lower
      sexual risk status was significantly associated with positive partner norms
      toward safer sex and with favorable partner reaction outcome expectancies.
      Interaction effects between gender and sexual risk level were found. Outcome
      expectancies related to approval from others for safer sex were lowest for
      females in the low-risk group and for males in the high-risk group. Females
      perceived peers as more positive about safer sex practices, while males perceived
      sexual partners as more positive. Additionally, females had higher self-efficacy
      for making condom use enjoyable and planning to avoid risk situations, but were
      less comfortable than males when demonstrating condom skills. Adolescents' HIV
      prevention programs must be tailored for gender and risk status.

PMID- 9585497
TI  - Adolescents who take overdoses: outcome in terms of changes in psychopathology
      and the adolescents' attitudes to care and to their overdose.
AB  - Adolescent self-poisoners were followed up 3 months after taking an overdose.
      High levels of psychopathology were found, with 72% (18/25) of the adolescents
      having a diagnosable psychiatric disorder and 48% (12/25) major depression. All
      the adolescents were offered follow-up treatment from health or social services.
      Compliance with treatment was very high. Seventy-two per cent of the adolescents
      found treatment useful to them. The adolscents received a generally sympathetic
      response from their significant others. Fifty-four per cent of the adolescents
      thought that their overdose had resulted overall in improvements to their lives
      but 44% would consider taking an overdose again in similar circumstances.

PMID- 9585498
TI  - Academic achievement, motivation and possible selves.

PMID- 9585499
TI  - SAPKs and transcription factors do the nucleocytoplasmic tango.

PMID- 9585500
TI  - Regulation of gene expression by TBP-associated proteins.

PMID- 9585501
TI  - Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis.
AB  - The U2 snRNP component SAP 155 contacts pre-mRNA on both sides of the branch site
      early in spliceosome assembly and is therefore positioned near or at the
      spliceosome catalytic center. We have isolated a cDNA encoding human SAP 155 and
      identified its highly related Saccharomyces cerevisiae homolog (50% identity).
      The carboxy-terminal two-thirds of SAP 155 shows the highest conservation and is
      remarkably similar to the regulatory subunit A of the phosphatase PP2A.
      Significantly, SAP 155 is phosphorylated concomitant with or just after catalytic
      step one, making this the first example of a protein modification tightly
      regulated with splicing catalysis.

PMID- 9585502
TI  - Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation
      of target proteins through a Ras-independent pathway.
AB  - Oncogenic forms of the Abl and Src tyrosine kinases trigger the destruction of
      the Abi proteins, a family of Abl-interacting proteins that antagonize the
      oncogenic potential of Abl after overexpression in fibroblasts. The destruction
      of the Abi proteins requires tyrosine kinase activity and is dependent on the
      ubiquitin-proteasome pathway. We show that degradation of the Abi proteins occurs
      through a Ras-independent pathway. Significantly, expression of the Abi proteins
      is lost in cell lines and bone marrow cells isolated from patients with
      aggressive Bcr-Abl-positive leukemias. These findings suggest that loss of Abi
      proteins may be a component in the progression of Bcr-Abl-positive leukemias and
      identify a novel pathway linking activated nonreceptor protein tyrosine kinases
      to the destruction of specific target proteins through the ubiquitin-proteasome
      pathway.

PMID- 9585503
TI  - clr-1 encodes a receptor tyrosine phosphatase that negatively regulates an FGF
      receptor signaling pathway in Caenorhabditis elegans.
AB  - Receptor tyrosine phosphatases have been implicated in playing important roles in
      cell signaling events by their ability to regulate the level of protein tyrosine
      phosphorylation. Although the catalytic activity of their phosphatase domains has
      been well established, the biological roles of these molecules are, for the most
      part, not well understood. Here we show that the Caenorhabditis elegans protein
      CLR-1 (CLeaR) is a receptor tyrosine phosphatase (RTP) with a complex
      extracellular region and two intracellular phosphatase domains. Mutations in clr
      1 result in a dramatic Clr phenotype that we have used to study the physiological
      requirements for the CLR-1 RTP. We show that the phosphatase activity of the
      membrane-proximal domain is essential for the in vivo function of CLR-1. By
      contrast, we present evidence that the membrane-distal domain is not required to
      prevent the Clr phenotype in vivo. The Clr phenotype of clr-1 mutants is mimicked
      by activation of the EGL-15 fibroblast growth factor receptor (FGFR) and is
      suppressed by mutations that reduce or eliminate the activity of egl-15. Our data
      strongly indicate that CLR-1 attenuates the action of an FGFR-mediated signaling
      pathway by dephosphorylation.

PMID- 9585504
TI  - Noggin-mediated antagonism of BMP signaling is required for growth and patterning
      of the neural tube and somite.
AB  - Embryonic patterning in vertebrates is dependent upon the balance of inductive
      signals and their specific antagonists. We show that Noggin, which encodes a bone
      morphogenetic protein (BMP) antagonist expressed in the node, notochord, and
      dorsal somite, is required for normal mouse development. Although Noggin has been
      implicated in neural induction, examination of null mutants in the mouse
      indicates that Noggin is not essential for this process. However, Noggin is
      required for subsequent growth and patterning of the neural tube. Early BMP
      dependent dorsal cell fates, the roof plate and neural crest, form in the absence
      of Noggin. However, there is a progressive loss of early, Sonic hedgehog (Shh)
      dependent ventral cell fates despite the normal expression of Shh in the
      notochord. Further, somite differentiation is deficient in both muscle and
      sclerotomal precursors. Addition of BMP2 or BMP4 to paraxial mesoderm explants
      blocks Shh-mediated induction of Pax-1, a sclerotomal marker, whereas addition of
      Noggin is sufficient to induce Pax-1. Noggin and Shh induce Pax-1
      synergistically. Use of protein kinase A stimulators blocks Shh-mediated
      induction of Pax-1, but not induction by Noggin, suggesting that induction is
      mediated by different pathways. Together these data demonstrate that inhibition
      of BMP signaling by axially secreted Noggin is an important requirement for
      normal patterning of the vertebrate neural tube and somite.

PMID- 9585505
TI  - Regulation of the fission yeast transcription factor Pap1 by oxidative stress:
      requirement for the nuclear export factor Crm1 (Exportin) and the stress
      activated MAP kinase Sty1/Spc1.
AB  - The fission yeast Sty1 stress-activated MAP kinase is crucial for the cellular
      response to a variety of stress conditions. Accordingly, sty1- cells are
      defective in their response to nutrient limitation, lose viability in stationary
      phase, and are hypersensitive to osmotic stress, oxidative stress, and UV
      treatment. Some of these phenotypes are caused by Sty1-dependent regulation of
      the Atf1 transcription factor, which controls both meiosis-specific and osmotic
      stress-responsive genes. However, in this report we demonstrate that the cellular
      response to oxidative stress and to treatment with a variety of cytotoxic agents
      is the result of Sty1 regulation of the Pap1 transcription factor, a bZip protein
      with structural and DNA binding similarities to the mammalian c-Jun protein. We
      show that both Sty1 and Pap1 are required for the expression of a number of genes
      involved in the oxidative stress response and for the expression of two genes,
      hba2+/bfr1+ and pmd1+, which encode energy-dependent transport proteins involved
      in multidrug resistance. Furthermore, we demonstrate that Pap1 is regulated by
      stress-dependent changes in subcellular localization. On imposition of oxidative
      stress, the Pap1 protein relocalizes from the cytoplasm to the nucleus in a
      process that is dependent on the Sty1 kinase. This relocalization is the result
      of regulated protein export, rather than import, and involves the Crm1 (exportin)
      nuclear export factor and the dcd1+/pim1+ gene that encodes an Ran nucleotide
      exchange factor.

PMID- 9585506
TI  - Phosphorylation and association with the transcription factor Atf1 regulate
      localization of Spc1/Sty1 stress-activated kinase in fission yeast.
AB  - Control of gene expression by stress-activated protein kinase (SAPK) cascades is
      crucial for combating cytotoxic stress. Elements of these cascades have been
      investigated in detail, but regulation of stress signal transduction from the
      cytoplasm to the nucleus is poorly understood. Herein are reported subcellular
      localization studies of fission yeast Spc1, a homolog of human p38 and budding
      yeast Hog1p SAPKs. Stress induces transient nuclear localization of Spc1. Nuclear
      translocation of Spc1 is coupled with disassociation from its activator kinase
      Wis1. However, Spc1 does not concentrate in the nucleus of Deltawis1 cells;
      therefore Wis1 does not tether Spc1 in the cytoplasm. Unphosphorylatable forms of
      Spc1 are dispersed in the cytoplasm and nucleus, even in cells that also produce
      wild-type Spc1. Thus, Spc1 must be phosphorylated by Wis1 to localize in the
      nucleus. Nuclear retention of Spc1 requires Atf1, a transcription factor that is
      the key nuclear substrate of Spc1. Nuclear localization of Atf1 requires Pcr1, a
      heterodimerization partner of Atf1. These studies show that phosphorylation and
      association with Atf1 are required for nuclear localization of Spc1.

PMID- 9585507
TI  - Ultrabithorax regulates genes at several levels of the wing-patterning hierarchy
      to shape the development of the Drosophila haltere.
AB  - Arthropods and vertebrates are constructed of many serially homologous structures
      whose individual patterns are regulated by Hox genes. The Hox-regulated target
      genes and developmental pathways that determine the morphological differences
      between any homologous structures are not known. The differentiation of the
      Drosophila haltere from the wing through the action of the Ultrabithorax (Ubx)
      gene is a classic example of Hox regulation of serial homology, although no Ubx
      regulated genes in the haltere have been identified previously. Here, we show
      that Ubx represses the expression of the Wingless (Wg) signaling protein and a
      subset of Wg- and Decapentaplegic-activated genes such as spalt-related,
      vestigial, Serum Response Factor, and achaete-scute, whose products regulate
      morphological features that differ between the wing and haltere. In addition, we
      found that some genes in the same developmental pathway are independently
      regulated by Ubx. Our results suggest that Ubx, and Hox genes in general,
      independently and selectively regulate genes that act at many levels of
      regulatory hierarchies to shape the differential development of serially
      homologous structures.

PMID- 9585508
TI  - pavarotti encodes a kinesin-like protein required to organize the central spindle
      and contractile ring for cytokinesis.
AB  - Mutations in the Drosophila gene pavarotti result in the formation of abnormally
      large cells in the embryonic nervous system. In mitotic cycle 16, cells of pav
      mutant embryos undergo normal anaphase but then develop an abnormal telophase
      spindle and fail to undertake cytokinesis. We show that the septin Peanut, actin,
      and the actin-associated protein Anillin, do not become correctly localized in
      pav mutants. pav encodes a kinesin-like protein, PAV-KLP, related to the
      mammalian MKLP-1. In cellularized embryos, the protein is localized to
      centrosomes early in mitosis, and to the midbody region of the spindle in late
      anaphase and telophase. We show that Polo kinase associates with PAV-KLP with
      which it shows an overlapping pattern of subcellular localization during the
      mitotic cycle and this distribution is disrupted in pav mutants. We suggest that
      PAV-KLP is required both to establish the structure of the telophase spindle to
      provide a framework for the assembly of the contractile ring, and to mobilize
      mitotic regulator proteins.

PMID- 9585509
TI  - Exit from mitosis in Drosophila syncytial embryos requires proteolysis and cyclin
      degradation, and is associated with localized dephosphorylation.
AB  - The cyclin proteolysis that accompanies the exit from mitosis in diverse systems
      appears to be essential for restoration of interphase. The early syncytial
      divisions of Drosophila embryos, however, occur without detectable oscillations
      in the total cyclin level or Cdk1 activity. Nonetheless, we found that injection
      of an established inhibitor of cyclin proteolysis, a cyclin B amino-terminal
      peptide, prevents exit from mitosis in syncytial embryos. Similarly, injection of
      a version of Drosophila cyclin B that is refractory to proteolysis results in
      mitotic arrest. We infer that proteolysis of cyclins is required for exit from
      syncytial mitoses. This inference can be reconciled with the failure to observe
      oscillations in total cyclin levels if only a small pool of cyclins is destroyed
      in each cycle. We find that antibody detection of histone H3 phosphorylation
      (PH3) acts as a reporter for Cdk1 activity. A gradient of PH3 along anaphase
      chromosomes suggests local Cdk1 inactivation near the spindle poles in syncytial
      embryos. This pattern of Cdk1 inactivation would be consistent with local cyclin
      destruction at centrosomes or kinetochores. The local loss of PH3 during anaphase
      is specific to the syncytial divisions and is not observed after cellularization.
      We suggest that exit from mitosis in syncytial cycles is modified to allow
      nuclear autonomy within a common cytoplasm.

PMID- 9585510
TI  - Modulation of telomerase activity by telomere DNA-binding proteins in Oxytricha.
AB  - Telomere proteins protect the chromosomal terminus from nucleolytic degradation
      and end-to-end fusion, and they may contribute to telomere length control and the
      regulation of telomerase. The current studies investigate the effect of Oxytricha
      single-stranded telomere DNA-binding protein subunits alpha and beta on
      telomerase elongation of telomeric DNA. A native agarose gel system was used to
      evaluate telomere DNA-binding protein complex composition, and the ability of
      telomerase to use these complexes as substrates was characterized. Efficient
      elongation occurred in the presence of the alpha subunit. Moreover, the alpha-DNA
      cross-linked complex was a substrate for telomerase. At higher alpha
      concentrations, two alpha subunits bound to the 16-nucleotide single-stranded DNA
      substrate and rendered it inaccessible to telomerase. The formation of this alpha
      . DNA . alpha complex may contribute to regulation of telomere length. The alpha
      . beta . DNA ternary complex was not a substrate for telomerase. Even when
      telomerase was prebound to telomeric DNA, the addition of alpha and beta
      inhibited elongation, suggesting that these telomere protein subunits have a
      greater affinity for the DNA and are able to displace telomerase. In addition,
      the ternary complex was not a substrate for terminal deoxynucleotidyltransferase.
      We conclude that the telomere protein inhibits telomerase by rendering the
      telomeric DNA inaccessible, thereby helping to maintain telomere length.

PMID- 9585511
TI  - The ATP-dependent PIM1 protease is required for the expression of intron
      containing genes in mitochondria.
AB  - The ATP-dependent PIM1 protease, a Lon-like protease localized in the
      mitochondrial matrix, is required for mitochondrial genome integrity in yeast.
      Cells lacking PIM1 accumulate lesions in the mitochondrial DNA (mtDNA) and
      therefore lose respiratory competence. The identification of a multicopy
      suppressor, which stabilizes mtDNA in the absence of PIM1, enabled us to
      characterize novel functions of PIM1 protease during mitochondrial biogenesis.
      The synthesis of mitochondrially encoded cytochrome c oxidase subunit I (CoxI)
      and cytochrome b (Cob) is impaired in pim1 mutants containing mtDNA. PIM1
      mediated proteolysis is required for the translation of mature COXI mRNA.
      Moreover, deficiencies in the splicing of COXI and COB transcripts, which appear
      to be restricted to introns encoding mRNA maturases, were observed in cells
      lacking the PIM1 gene. Transcripts of COXI and COB genes harboring multiple
      introns are degraded in the absence of PIM1. These results establish multiple,
      essential functions of the ATP-dependent PIM1 protease during mitochondrial gene
      expression.

PMID- 9585512
TI  - Spalten, a protein containing Galpha-protein-like and PP2C domains, is essential
      for cell-type differentiation in Dictyostelium.
AB  - We have identified a novel gene, Spalten (Spn) that is essential for
      Dictyostelium multicellular development. Spn encodes a protein with an amino
      terminal domain that shows very high homology to Galpha-protein subunits, a
      highly charged inter-region, and a carboxy-terminal domain that encodes a
      functional PP2C. Spn is essential for development past the mound stage, being
      required cell autonomously for prestalk gene expression and nonautonomously for
      prespore cell differentiation. Mutational analysis demonstrates that the PP2C
      domain is the Spn effector domain and is essential for Spn function, whereas the
      Galpha-like domain is required for membrane targeting and regulation of Spn
      function. Moreover, Spn carrying mutations in the Galpha-like domain that do not
      affect membrane targeting but affect specificity of guanine nucleotide binding in
      known GTP-binding proteins are unable to fully complement the spn- phenotype,
      suggesting that the Galpha-like domain regulates Spn function either directly or
      indirectly by mediating its interactions with other proteins. Our results suggest
      that Spn encodes a signaling molecule with a novel Galpha-like regulatory domain.

PMID- 9585514
TI  - Ultrafast carotenoid band shifts probe structure and dynamics in photosynthetic
      antenna complexes.
AB  - We report observations of ultrafast carotenoid band shifts correlated with energy
      transfer dynamics between bacteriochlorophyll (BChl) molecules within the
      peripheral light-harvesting complex (LH2) from the photosynthetic bacterium
      Rhodobacter sphaeroides. Direct excitation of the bacteriochlorophyll Qy bands
      yielded distinct changes in the carotenoid S2 absorption from 430 to 530 nm.
      Transient absorption spectra and kinetics were measured in a femtosecond pump
      probe experiment, revealing the ultrafast carotenoid response to excited BChl
      pigments. These data are an indication of a new property of carotenoids that is
      manifested as a unique ability to detect and report changes in their immediate
      environment, thereby serving as sensitive probes of local structure and dynamics.

PMID- 9585513
TI  - The competence transcription factor of Bacillus subtilis recognizes short A/T
      rich sequences arranged in a unique, flexible pattern along the DNA helix.
AB  - The development of genetic competence in Bacillus subtilis is regulated by a
      complex signal transduction cascade, which leads to the synthesis of the
      competence transcription factor (CTF). Previous studies suggested that CTF is
      encoded by comK. ComK is required for the transcription of comK itself, as well
      as of the late competence genes encoding the DNA uptake machinery and of genes
      required for homologous recombination. Here, we used purified ComK to study its
      role in transcription and to determine the DNA recognition sequence for ComK. In
      vitro transcription from the comG promoter, which depends on ComK in vivo, was
      observed on the addition of purified ComK together with Bacillus subtilis RNA
      polymerase, proving that ComK is CTF. To determine the DNA sequences involved in
      ComK recognition, footprinting analysis was performed with promoter fragments of
      the CTF-dependent genes: comC, comE, comF, comG, comK, and addAB. The ComK
      binding sites determined by DNase I protection experiments were unusually long,
      with average lengths of approximately 65 bp, and displayed only weak sequence
      similarities. Hydroxy-radical footprinting, performed with the addAB promoter,
      revealed a unique arrangement of four short A/T-rich sequences. Gel retardation
      experiments indicated that four molecules of ComK bound the addAB promoter and
      the dyad symmetrical arrangement of the four A/T-rich sequences implied that ComK
      functions as a tetramer composed of two dimers each recognizing the motif
      AAAAN5TTTT. Comparable A/T-rich sequences were identified in all six DNase I
      footprints and could be used to predict ComK targets in the B. subtilis genome.
      On the basis of the variability in distance between the ComK-dimer binding sites,
      ComK-regulated promoters could be divided into three classes, demonstrating a
      remarkable flexibility in the binding of ComK. The pattern of hydroxy-radical
      protections suggested that ComK binds at one face of the DNA helix through the
      minor groove. This inference was strengthened by the observation that minor
      groove binding drugs inhibited the binding of ComK.

PMID- 9585515
TI  - Direct measurement of small ligand-induced conformational changes in the
      aspartate chemoreceptor using EPR.
AB  - Ligand-binding-induced conformational changes in the Salmonella typhimurium
      aspartate receptor were studied using spin-labeling electron paramagnetic
      resonance. Cysteine residues, introduced by site-directed mutagenesis at several
      positions in the aspartate receptor periplasmic domain, were used to attach
      covalently a thiol-specific spin label. The electron paramagnetic resonance
      spectra of these labeled proteins were obtained in the presence and absence of
      the ligand aspartate, and used to calculate the distance change between spin
      labels. The results support a model in which transmembrane signaling is executed
      by a combined movement of alpha helix 4 (which leads into transmembrane domain 2)
      relative to alpha helix 1 (connected to transmembrane domain 1), as well as a
      coming together of the two subunits. Ligand binding causes spin labels at
      position 39 and 179 (within one subunit) to move further from each other and spin
      labels at position 39 and 39' (between two subunits) to move closer to each
      other. Both of these changes are very small-less than 2.5 A. No similar changes
      were detected in any aspartate receptor samples solubilized in detergent,
      suggesting that the membrane is required for these conformational changes. This
      is the first case of physically measured ligand-induced changes in a full-length
      1-2 transmembrane domain receptor, and the results suggest that very small ligand
      induced movements can result in large effects on the activity of downstream
      proteins.

PMID- 9585516
TI  - Construction of a novel redox protein by rational design: conversion of a
      disulfide bridge into a mononuclear iron-sulfur center.
AB  - A mononuclear iron-sulfur center, capable of reversible electron transfer, has
      been introduced into thioredoxin, a protein devoid of such sites, using an
      automated, structure-based design algorithm. One of the sites predicted by the
      Dezymer computer program to introduce a tetrahedral tetrathiolate iron center
      included the intrinsic Cys32-Cys35 disulfide of wild-type thioredoxin and two
      additional mutants, Trp28Cys and Ile75Cys, thereby converting a disulfide into a
      metal-based redox center. This designed protein forms a 1:1 monomeric complex
      with FeIII, whose electronic absorption and EPR spectra closely resemble those of
      the rubredoxins, as intended. CoII spectra provided further confirmation of
      tetrahedral tetrathiolate metal coordination. The designed protein is capable of
      undergoing successive cycles of oxidation and reduction. The computer-generated
      design only took into account the geometry of the primary coordination shell
      around the metal. We have therefore demonstrated that simple geometrical
      considerations can be sufficient to reproduce the dominant electronic structure
      and reactivity of a simple metal-based redox center.

PMID- 9585517
TI  - Histone H1 binding does not inhibit transcription of nucleosomal Xenopus laevis
      somatic 5S rRNA templates.
AB  - It has long been proposed that selective binding of histone H1 is, in part,
      responsible for the differential developmental regulation of the oocyte and
      somatic 5S rRNA genes in Xenopus laevis. In this study we show that histone H1
      binds both oocyte and somatic genes equally after reconstitution into
      mononucleosomes or oligonucleosome arrays. Furthermore, we show that the binding
      of histone H1 selectively represses only oocyte gene transcription and that an
      RNA polymerase III transcription complex is able to initiate transcription of
      nucleosomal somatic templates regardless of whether histone H1 is present. These
      results support a model in which the differential regulation of the 5S rRNA genes
      is not simply due to the prevention of histone H1 binding by transcription
      complexes on the somatic genes, but rather to a difference in the histone H1
      interaction with the somatic and oocyte genes.

PMID- 9585518
TI  - Transient kinetic analysis of adenosine 5'-triphosphate binding-induced
      conformational changes in the allosteric chaperonin GroEL.
AB  - GroEL with an intrinsic fluorescent probe was generated by introducing the
      mutation Phe44 --> Trp. Different concentrations of ATP were rapidly mixed with
      GroEL containing this mutation, and the time-resolved change in fluorescence
      emission, upon excitation at 280 nm, was followed. Three kinetic phases were
      observed: a fast phase with a large amplitude and two slower phases with small
      amplitudes. The phases were assigned by (i) determining their dependence on ATP
      concentration; (ii) measuring their sensitivity to the mutation Arg197 --> Ala,
      which decreases cooperativity in ATP binding; and (iii) by carrying out mixing
      experiments of GroEL also with ADP, ATPgammaS, and ATP without K+. The apparent
      rate constant corresponding to the fast phase displays a bi-sigmoidal dependence
      on ATP concentration with Hill coefficients that are strikingly similar to those
      determined in steady-state experiments. This phase, which reflects ATP-induced
      conformational changes, is sensitive to the mutation Arg197 --> Ala in a manner
      that parallels steady-state experiments. The rate of conformational change in the
      presence of ATP is >100 sec-1, which is fast relative to most protein folding
      rates, whereas in the absence of ATP it is approximately 0.7 s-1. The second
      phase reflects the transition from an ATP-bound state of GroEL to an ADP-bound
      state. The third phase, with the smallest amplitude, reflects release of residual
      contaminants. The results in this study are found to be consistent with the
      nested model for cooperativity in ATP binding by GroEL [Yifrach, O., and
      Horovitz, A. (1995) Biochemistry 34, 5303-5308].

PMID- 9585519
TI  - A structural role for glutamine 214 in human thymidylate synthase.
AB  - Studies of the crystal structures of thymidylate synthase (TS) have revealed that
      a kink is present in beta-sheets that form the core of the enzyme. The beta-kink
      is proposed to serve as a "hinge" during conformational changes that occur in the
      enzyme after ligand binding at the active site. A residue in one of the beta
      bulges that form the kink, glutamine at position 214 of human TS, is highly
      conserved in all TSs and is postulated to interact with nucleotide ligands that
      bind at the active site. To examine the role of this residue, glutamine at
      position 214 was replaced by residues that differ in volume, hydrophobicity,
      electrostatic charge, and hydrogen bonding potential. Genetic complementation
      studies utilizing a TS-deficient bacterial strain revealed that residues with
      large side chain volumes or that are prohibited in beta-bulges created loss of
      function proteins. Kinetic studies indicated that residue hydrophobicity is not
      correlated with catalytic activity. Residues that are predicted to alter the
      charge at position 214 created enzymes with kcat/Km values at least 10(3) lower
      than those of the wild type. Kinetic and ligand binding studies indicated that
      residue 214 is involved in nucleotide binding; however, hydrogen bonding
      potential does not contribute significantly to nucleotide binding energy. The
      data are consistent with the hypothesis that residue 214 is involved in
      maintaining the enzyme in a conformation that facilitates nucleotide binding and
      catalysis.

PMID- 9585520
TI  - A hydroxyl group at residue 216 is essential for catalysis by human thymidylate
      synthase.
AB  - Structural analyses of bacterial thymidylate synthases (TSs) implicate a serine
      residue corresponding to Ser216 in human TS in hydrogen bond networks that are
      involved in binding of the nucleotide substrate, 2'-deoxyuridylate (dUMP), and
      that stabilize a beta-bulge in the protein. Utilizing site-directed mutagenesis,
      12 mutant proteins were created with substitutions at residue 216. DNA
      complementation studies utilizing a TS-negative bacterial strain revealed that
      only one mutant, Thr216 TS, supports the growth of the bacteria in the absence of
      thymidine. Kinetic characterization of the mutant proteins revealed that all TSs
      except Thr216 TS exhibited kcat/Kms for dUMP that are 10(3)-10(4) times lower,
      relative to that of wild-type TS. In addition, Thr216 TS was the only mutant to
      bind the mechanism-based inhibitor, 5-fluoro-2'-deoxyuridylate (FdUMP), into a
      ternary complex. Ligand binding studies revealed that Kds for dUMP binding to two
      defective mutants, Ala216 and Leu216 TSs, are 12-16-fold higher than that of wild
      type TS. The data are consistent with the hypothesis that serine at this relative
      position is involved in dUMP binding; however, the data indicate that Ser216 has
      effects on catalysis, in addition to effects on dUMP binding. Catalysis is
      initiated by nucleophilic attack of the active site cysteine of TS on dUMP. The
      reaction rates of cysteine residues with the sulfhydryl reagent 5,5'-dithiobis(2
      nitrobenzoic acid) were slower for Ala216 TS than for wild-type TS.

PMID- 9585521
TI  - Crystal structure of ErmC', an rRNA methyltransferase which mediates antibiotic
      resistance in bacteria.
AB  - The prevalent mechanism of bacterial resistance to erythromycin and other
      antibiotics of the macrolide-lincosamide-streptogramin B group (MLS) is
      methylation of the 23S rRNA component of the 50S subunit in bacterial ribosomes.
      This sequence-specific methylation is catalyzed by the Erm group of
      methyltransferases (MTases). They are found in several strains of pathogenic
      bacteria, and ErmC is the most studied member of this class. The crystal
      structure of ErmC' (a naturally occurring variant of ErmC) from Bacillus subtilis
      has been determined at 3.0 A resolution by multiple anomalous diffraction phasing
      methods. The structure consists of a conserved alpha/beta amino-terminal domain
      which binds the cofactor S-adenosyl-l-methionine (SAM), followed by a smaller,
      alpha-helical RNA-recognition domain. The beta-sheet structure of the SAM-binding
      domain is well-conserved between the DNA, RNA, and small-molecule MTases.
      However, the C-terminal nucleic acid binding domain differs from the DNA-binding
      domains of other MTases and is unlike any previously reported RNA-recognition
      fold. A large, positively charged, concave surface is found at the interface of
      the N- and C-terminal domains and is proposed to form part of the protein-RNA
      interaction surface. ErmC' exhibits the conserved structural motifs previously
      found in the SAM-binding domain of other methyltransferases. A model of SAM bound
      to ErmC' is presented which is consistent with the motif conservation among
      MTases.

PMID- 9585522
TI  - Sequence determinants of the intrinsic bend in the cyclic AMP response element.
AB  - The cyclic AMP response element (CRE site, ATGACGTCAT) is the DNA target for
      transcription factors whose activities are regulated by cyclic AMP (1). Recently,
      we discovered that the CRE site is bent by 10-13 degrees toward the major groove
      (2). Little or no bend is detected in the related AP-1 site (ATGACTCAT), which
      differs from the CRE site by loss of a single, central, C.G base pair (2, 3).
      Here we describe experiments designed to identify which base pairs within the CRE
      site induce the bent structure in an attempt to understand the origins of the
      dramatically different conformations of the CRE and AP-1 sites. Our data indicate
      that the intrinsic CRE bend results from distortion within the TGA sequence found
      in each CRE half site (ATGAC). These two TGA sequences are located in phase with
      one another in the CRE sequence but are not (completely) in phase in the AP-1
      sequence. This difference in phasing leads to the overall difference in bend as
      detected by gel (2) and cyclization methods (S. C. Hockings, J. D. Kahn, and D.
      M. Crothers, unpublished results; M. A. Fabian and A. Schepartz, unpublished
      results). Our results confirm earlier predictions of altered structure within TG
      steps, provide insight into the structural reorganizations induced in DNA by bZIP
      proteins, and lead to a revision of the relationship between the structures of
      the free and bZIP-bound forms of the CRE and AP-1 sites.

PMID- 9585523
TI  - Self-association and backbone dynamics of the hck SH2 domain in the free and
      phosphopeptide-complexed forms.
AB  - Decreased dynamic motion in the peptide backbone of proteins may accompany ligand
      binding and influence the thermodynamic and kinetic stability of the resulting
      complexes. We have investigated the diffusional behavior and backbone dynamics of
      the free and phosphopeptide (EPQpYEEIPIYL) complexed Hck SH2 domain using NMR
      spectroscopy. Both the free domain and its phosphopeptide complex self-associate
      at higher protein concentrations. Diffusional measurements and surface analysis
      indicate that charged side-chain groups are probably responsible for self
      association. Higher order aggregation, such as trimer and tetramer, also occurs
      at elevated protein concentrations. Dynamic motion in the peptide backbone of Hck
      SH2 was determined from 15N relaxation data fit using extended model-free
      parameters. The rotational correlation time (taum) for uncomplexed Hck SH2 was
      6.8 ns while taum for peptide-bound Hck SH2 was 7.6 ns. Generalized order
      parameters (S2) increased for most residues upon binding of the phosphopeptide,
      consistent with peptide binding restricting motion of the NH bond vectors on the
      picosecond time scale. These studies suggest that complexation increases internal
      order in Hck SH2 and that internal dynamic motions contribute to the activation
      of Src-family kinases in vivo.

PMID- 9585524
TI  - Structure and intramodular dynamics of the amino-terminal LIM domain from quail
      cysteine- and glycine-rich protein CRP2.
AB  - Members of the cysteine and glycine-rich protein (CRP) family (CRP1, CRP2, and
      CRP3) contain two zinc-binding LIM domains, LIM1 and LIM2, and are implicated in
      diverse cellular processes linked to differentiation, growth control and
      pathogenesis. The solution structure of an 81-amino acid recombinant peptide
      encompassing the amino-terminal LIM1 domain of quail CRP2 has been determined by
      2D and 3D homo- and heteronuclear NMR spectroscopy. The LIM1 domain consists of
      two zinc binding sites of the CCHC and the CCCC type, respectively, which both
      contain two orthogonally arranged antiparallel beta-sheets and which are packed
      together by a hydrophobic core composed of residues from the zinc finger loop
      regions. The CCCC zinc finger is followed by a short alpha-helical stretch. The
      structural analysis revealed that the global fold of LIM1 closely resembles the
      recently determined solution structures of the carboxyl-terminal LIM2 domains of
      quail CRP2 and chicken CRP1, and that LIM1 and LIM2 are independently folded
      structural and presumably functional domains of CRP proteins. To explore the
      dynamical properties of CRP proteins, we have used 15N relaxation values (T1, T2,
      and nuclear Overhauser effect (NOE) to describe the dynamical behavior of a LIM
      domain. A model-free analysis revealed local variations in mobility along the
      backbone of the quail CRP2 LIM1 motif. Slow motions are evident in turn regions
      located between the various antiparallel beta-sheets or between their strands. By
      use of an extended motional model, fast backbone motions were detected for
      backbone amide NH groups of hydrophobic residues located in the core region of
      the LIM1 domain. These findings point to a flexible hydrophobic core in the LIM1
      domain allowing residual relative mobility of the two zinc fingers, which might
      be important to optimize the LIM1 interface for interaction with its
      physiological target molecule(s) and to compensate enthalpically for the entropy
      loss upon binding.

PMID- 9585526
TI  - Mutational analysis of novel effector domains in Rac1 involved in the activation
      of nicotinamide adenine dinucleotide phosphate (reduced) oxidase.
AB  - The small molecular weight GTP-binding protein Rac (1 or 2) is an obligatory
      participant in the activation of the superoxide-generating NADPH oxidase. Active
      NADPH oxidase can be reconstituted in a cell-free system, consisting of phagocyte
      derived membranes, containing cytochrome b559, and the recombinant cytosolic
      proteins p47-phox, p67-phox, and Rac, supplemented with an anionic amphiphile as
      an activator. The cell-free system was used before for the analysis of structural
      requirements of individual components participating in the assembly of NADPH
      oxidase. In earlier work, we mapped four previously unidentified domains in Rac1,
      encompassing residues 73-81 (a), 103-107 (b), 123-133 (c), and 163-169 (d), as
      important for cell-free NADPH oxidase activation. The domains were defined by
      assessing the activation inhibitory effect of a series of overlapping peptides,
      spanning the entire length of Rac1 [Joseph, G., and Pick, E. (1995) J. Biol.
      Chem. 270, 29079-29082]. We now used the construction of Rac1/H-Ras chimeras,
      domain deletion, and point mutations, to ascertain the functional relevance of
      three domains (b, c, and d) predicted by "peptide walking" and to determine the
      importance of specific residues within these domains. This methodology firmly
      establishes the involvement of domains b and d in the activation of NADPH oxidase
      by Rac1 and identifies H103 and K166, respectively, as residues critical for the
      effector function of these two domains. The functional significance of domain c
      (insert region) could not be confirmed, as shown by the minor effect of deleting
      this domain on NADPH oxidase activation. Analysis of the three-dimensional
      structure of Rac1 reveals that residues H103 and K166 are exposed on the surface
      of the molecule. Modeling of the activity-impairing point mutations suggests that
      the effect on the ability to activate NADPH oxidase depends on the side chains of
      the mutated amino acids and not on changes in the global structure of the
      protein. In conclusion, we demonstrate the existence of two novel effector sites
      in Rac1, necessary for supporting NADPH oxidase activation, supplementing the
      canonical N-terminal effector region.

PMID- 9585525
TI  - Calf spleen purine nucleoside phosphorylase complexed with substrates and
      substrate analogues.
AB  - Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine salvage
      pathway, which provides an alternative to the de novo pathway for the
      biosynthesis of purine nucleotides. PNP catalyzes the reversible phosphorolysis
      of 2'-deoxypurine ribonucleosides to the free bases and 2-deoxyribose 1
      phosphate. Absence of PNP activity in humans is associated with specific T-cell
      immune suppression. Its key role in these two processes has made PNP an important
      drug design target. We have investigated the structural details of the PNP
      catalyzed reaction by determining the structures of bovine PNP complexes with
      various substrates and substrate analogues. The preparation of phosphate-free
      crystals of PNP has allowed us to analyze several novel complexes, including the
      ternary complex of PNP, purine base, and ribose 1-phosphate and of the completely
      unbound PNP. These results provide an atomic view for the catalytic mechanism for
      PNP proposed by M. D. Erion et al. [(1997) Biochemistry 36, 11735-11748], in
      which an oxocarbenium intermediate is stabilized by phosphate and the negative
      charge on the purine base is stabilized by active site residues. The bovine PNP
      structure reveals several new details of substrate and inhibitor binding,
      including two phosphate-induced conformational changes involving residues 33-36
      and 56-69 and a previously undetected role for His64 in phosphate binding. In
      addition, a well-ordered water molecule is found in the PNP active site when
      purine base or nucleoside is also present. In contrast to human PNP, only one
      phosphate binding site was observed. Although binary complexes were observed for
      nucleoside, purine base, or phosphate, ribose 1-phosphate binding occurs only in
      the presence of purine base.

PMID- 9585527
TI  - A search for single substitutions that eliminate enzymatic function in a
      bacterial ribonuclease.
AB  - Exhaustive-substitution studies, where many amino acid replacements are
      individually tested at all positions in a natural protein, have proven to be very
      valuable in probing the relationship between sequence and function. The broad
      picture that has emerged from studies of this sort is one of functional tolerance
      of substitution. We have applied this approach to barnase, a 110-residue
      bacterial ribonuclease. Because the selection system used to score barnase
      mutants as active or inactive detects activity down to a level that can be
      approached by nonenzyme catalysts, mutants that test inactive are essentially
      devoid of enzymatic function. Of the 109 barnase positions subjected to
      substitution, only 15 (14%) are vulnerable to this extreme level of inactivation,
      and only 2 could not be substituted without such inactivation. A total of 33
      substitutions (amounting to 5% of the explored substitutions) were found to
      render barnase wholly inactive. The profoundly disruptive effects of all of these
      inactivating substitutions appear to result from either (1) replacement of a side
      chain that is directly involved in substrate binding or catalysis, (2)
      replacement of a substantially buried side chain, (3) introduction of a proline
      residue, or (4) replacement of a glycine residue. Although substitutions of these
      types are functionally tolerated more often than not, the system used here
      indicates that only these sorts of substitution are capable of single-handedly
      reducing catalytic function to, or nearly to, levels that can be achieved by
      nonenzyme catalysts.

PMID- 9585528
TI  - Prodan fluorescence reflects differences in nucleotide-induced conformational
      states in the myosin head and allows continuous visualization of the ATPase
      reactions.
AB  - The noncovalent fluorescent probe 6-propionyl-2-(dimethylamino)naphthalene
      (prodan) binds stoichiometrically to myosin subfragment-1 (S-1) without affecting
      the ATPase and actin-binding properties of S-1. Neither ATP nor actin interferes
      with the prodan binding. Free prodan exhibits a green emission peak at 520 nm.
      However, the prodan bound to S-1 and the S-1.ADP complex shows blue emission
      peaks at 460 and 450 nm, respectively, which allow easy separation of the
      fluorescence contributions from the free and bound probes. In the S-1.ADP.Pi
      state, the blue emission peak is further shifted to 445 nm with a large (4.5
      fold) fluorescence enhancement. Thus, prodan in the presence of S-1 exhibits
      predominantly blue fluorescence only during ATP hydrolysis, and so visualizes the
      ATPase reaction continuously. The initial velocities of the steady state of the
      Mg2+-, Ca2+-, and actin-activated ATPases can be conveniently calculated from the
      blue fluorescence changes. The ability of different nucleoside triphosphates
      (NTP) to enhance the blue fluorescence of prodan follows the order ATP > CTP >
      UTP > ITP > GTP. This order agrees with those of the extent of hydrophobicity
      near the ribose of the corresponding nucleoside diphosphates (NDP) trapped to S-1
      with orthovanadate (Vi) [Hiratsuka, T. (1984) J. Biochem. (Tokyo) 96, 155-162]
      and the ability of different NTPs to support force production in muscle fibers
      [Regnier, M., et al. (1993) Biophys. J. 64, A250]. The rate of formation of the
      corresponding S-1.NDP.Vi complex also follows this order, whereas the NTPase rate
      follows the reverse order. These results indicate that nucleotide-induced changes
      in prodan fluorescence correspond to the nucleotide-induced conformational states
      of S-1. Thus, the use of prodan in studies of the myosin ATPase offers a new and
      promising approach not only to monitoring the ATPase reaction but also to
      investigating the structural changes during ATP hydrolysis.

PMID- 9585529
TI  - Zinc-substituted hemoglobins: alpha- and beta-chain differences monitored by high
      resolution emission spectroscopy.
AB  - The absorption and emission properties of hybrid Zn-substituted human hemoglobin
      (Hb) were used to monitor differences in interaction between the porphyrin and
      the polypeptide chain for the two subunits. Although alpha-substituted (alpha
      ZnHb), beta-substituted (beta-ZnHb), or totally substituted Hb all show optical
      properties characteristic of Zn porphyrins, the spectra are also indicative of
      specific interactions between the polypeptide chain and the porphyrin. The Q0,0
      absorption band of alpha-ZnHb at 5 K shows a splitting of approximately 300 cm-1,
      comparable to the largest split ever reported for a heme protein. This value is
      approximately 140 cm-1 for beta-ZnHb. The possible origin of the split is
      discussed in terms of the local electric field imposed by the amino acids of the
      respective heme pockets, different configurations of the porphyrin, and/or
      influences of the liganding histidine. The Zn derivatives show quasiline spectra
      under fluorescence line narrowing conditions, and the resolved excitation
      spectrum reveals differences in the vibrational levels of the Zn porphyrin in the
      two subunits. Broad underlying emission in the fluorescence line-narrowed
      emission spectrum can be accounted for, in part, by the existence of the two
      closely spaced electronic origins and also by the extent of phonon coupling
      between the porphyrin and the protein matrix.

PMID- 9585530
TI  - Prion protein selectively binds copper(II) ions.
AB  - The infectious isoform of the prion protein (PrPSc) is derived from cellular PrP
      (PrPC) in a conversion reaction involving a dramatic reorganization of secondary
      and tertiary structure. While our understanding of the pathogenic role of PrPSc
      has grown, the normal physiologic function of PrPC still remains unclear. Using
      recombinant Syrian hamster prion protein [SHaPrP(29-231)], we investigated metal
      ions as possible ligands of PrP. Near-UV circular dichroism spectroscopy (CD)
      indicates that the conformation of SHaPrP(29-231) resembles PrPC purified from
      hamster brain. Here we demonstrate by CD and tryptophan (Trp) fluorescence
      spectroscopy that copper induces changes to the tertiary structure of SHaPrP(29
      231). Binding of copper quenches the Trp fluorescence emission significantly,
      shifts the emission spectrum to shorter wavelengths, and also induces changes in
      the near-UV CD spectrum of SHaPrP(29-231). The binding sites are highly specific
      for Cu2+, as indicated by the lack of a change in Trp fluorescence emission with
      Ca2+, Co2+, Mg2+, Mn2+, Ni2+, and Zn2+. Binding of Cu2+ also promotes the
      conformational shift from a predominantly alpha-helical to a beta-sheet
      structure. Equilibrium dialysis experiments indicate a binding stoichiometry of
      approximately 2 copper molecules per PrP molecule at physiologically relevant
      concentrations, and pH titration of Cu2+ binding suggests a role for histidine as
      a chelating ligand. NMR spectroscopy has recently demonstrated that the
      octarepeats (PHGGGWGQ) in SHaPrP(29-231) lack secondary or tertiary structure in
      the absence of Cu2+. Our results suggest that each Cu2+ binds to a structure
      defined by two octarepeats (PHGGGWGQ) with one histidine and perhaps one glycine
      carbonyl chelating the ion. We propose that the binding of two copper ions to
      four octarepeats induces a more defined structure to this region.

PMID- 9585531
TI  - Structures of five mutants of toxic shock syndrome toxin-1 with reduced
      biological activity.
AB  - The three-dimensional structures of five mutants of toxic shock syndrome toxin-1
      (TSST-1) have been determined. These mutations are in the long central alpha
      helix and are useful in mapping portions of TSST-1 involved in superantigenicity
      and lethality. The T128A, H135A, Q139K, and I140T mutations appear to reduce
      superantigenicity by altering the properties of the T-cell receptor interaction
      surface. The Q136A mutation is at a largely buried site and causes a dramatic
      change in the conformation of the beta7-beta9 loop which covers the back of the
      central alpha helix. As this mutation has the unique ability to reduce the
      toxin's lethality in rabbits while retaining its superantigenicity, it raises the
      possibility that this rear loop mediates the ability of TSST-1 to induce
      lethality and suggests a route for producing nonlethal toxins for therapeutic
      development.

PMID- 9585532
TI  - Conformational stability of factor VIIa: biophysical studies of thermal and
      guanidine hydrochloride-induced denaturation.
AB  - The binding of the multidomain protein factor VIIa (fVIIa) to tissue factor
      provides the interprotein communication necessary to make fVIIa an efficient
      catalyst of the initial event in the extrinsic pathway of blood coagulation. We
      have investigated the stability of individual domains in fVIIa and the influence
      of Ca2+ and an irreversible active-site inhibitor (FFR-chloromethyl ketone).
      Equilibrium guanidine hydrochloride (GuHCl)-induced unfolding monitored by
      tryptophan fluorescence and far-UV circular dichroism (CD) demonstrated that the
      gamma-carboxyglutamic acid (Gla) domain unfolds at 0.3 M GuHCl and the serine
      protease (SP) domain at 3 M GuHCl and that Ca2+ is a prerequisite for the
      formation of an ordered, compact structure in the Gla domain. The loss of
      amidolytic activity coincides with the first transition, which is stabilized by
      the active-site inhibitor, and a change in the environment of the active site is
      demonstrated using a fluorescent inhibitor (DEGR-chloromethyl ketone). Thermal
      unfolding monitored by differential scanning calorimetry (DSC) reveals that Ca2+
      stabilizes the SP domain slightly, increasing the unfolding temperature by 2.7
      degrees C. In addition, Ca2+ is required for a large enthalpy change concomitant
      with unfolding of the Gla domain, and this unfolding enthalpy is only detectable
      in the presence of the SP domain, indicating some kind of interaction between
      these domains. Thermal unfolding measured by CD indicates secondary structural
      changes at the same temperature as the heat absorption in the DSC but only when
      both the Gla domain and the SP domain are present together with Ca2+ ions. Taken
      together, these results indicate a Ca2+-dependent interaction between the Gla
      domain and the SP domain, implying a high degree of flexibility of the domains in
      free fVIIa. It is also shown that the epidermal growth factor-like domains are
      stable at elevated temperatures and high GuHCl concentrations. Moreover, already
      at physiological temperature, subtle structural changes take place which
      influence the overall shape of fVIIa and are detrimental to its enzymatic
      activity.

PMID- 9585533
TI  - Molecular cloning of the cDNA encoding the carboxy-terminal domain of chimpanzee
      apolipoprotein(a): an Asp57 --> Asn mutation in kringle IV-10 is associated with
      poor fibrin binding.
AB  - Insight into the structural features of human lipoprotein(a) [Lp(a)] which
      underlie its functional implication in fibrinolysis may be gained from
      comparative studies of apo(a). Indeed, cloning of rhesus monkey apo(a) has shown
      that a Trp72 --> Arg mutation in the lysine-binding site (LBS) of KIV-10 leads to
      loss of lysine-binding properties of the rhesus Lp(a) particle. Consequently,
      comparative studies of apo(a) sequences in different Old World monkey species
      should further our understanding of the molecular role of Lp(a) in the
      fibrinolytic process. In contrast to other Old World monkeys, including rhesus
      monkey, cynomolgus, and baboon, the chimpanzee exhibits an elevated level of
      Lp(a) and a distinct isoform distribution as compared to humans [Doucet et al. J.
      Lipid Res. (1994) 35, 263-270]. Clearly then, the chimpanzee is an interesting
      animal model for study of the structure, function, and potential
      pathophysiological roles of Lp(a). We have cloned and sequenced the region of
      chimpanzee apo(a) cDNA spanning KIV-3 to the stop codon. The global organization
      of this region is similar to that of human apo(a) with the presence of KV, which
      is absent in rhesus monkey apo(a). Nucleotide sequence comparison indicates a
      variation of 1.4% between chimpanzee and man and 5.1% between chimpanzee and
      rhesus monkey. The differences concerned single base changes. An Asp57 --> Asn
      mutation was detected in KIV-10; this residue is critical to the LBS of KIV-10 in
      human apo(a). To verify that the Asp57 --> Asn substitution was specific to
      apo(a), we have also cloned the cDNA-encoding plasminogen, which exhibited an Asp
      at the corresponding position in kringle IV. Using an in vitro binding assay, we
      have demonstrated that chimpanzee Lp(a) exhibits poor lysine-specific interaction
      with both intact and plasmin-degraded fibrin as compared to its human
      counterpart. We propose that the Asn57 substitution in KIV-10 of chimpanzee
      apo(a) is responsible for this property. Chimpanzee Lp(a) therefore represents an
      appropriate particle with which to explore the potential effects of Lp(a) on the
      fibrinolytic system, such as the inhibition of plasminogen activation or
      inhibition of t-PA activity.

PMID- 9585534
TI  - Copper-binding amyloid precursor protein undergoes a site-specific fragmentation
      in the reduction of hydrogen peroxide.
AB  - The extracellular domain of transmembrane Abeta amyloid precursor protein (APP)
      has a Cu(II) reducing activity upon Cu(II) binding associated with the formation
      of a new disulfide bridge. The complete assignment of the disulfide bond revealed
      the involvement of cysteines 144 and 158 around copper-binding histidine
      residues. The vulnerability of APP-Cu(I) complexes to reactive oxygen species was
      elaborated as a site-specific and random fragmentation of APP in a time-dependent
      manner and at low concentrations of H2O2. Analysis of the specific reaction
      revealed the generation of C-terminal polypeptides, containing the Abeta domain.
      APP catalyzed the reduction of H2O2 and oxidation of Cu(I) to Cu(II) in a
      "peroxidative" reaction in vitro. The resulting bound copper-hydroxyl radical
      intermediate [APP-Cu(II)(.OH)] then likely participated in a Fenton type of
      reaction with radical formation as a prerequisite for protein degradation.
      Evidence from two observations suggests that the reaction takes place in two
      phases. Bathocuproine, a trapping agent for Cu(I), abolished the initial
      fragmentation, and chelation of Cu(II) by DTPA (diethylenetriaminepentaacetic
      acid) interrupted the reaction cascade induced by H2O2 at later stages.
      Consequently, the results suggest that a cytotoxic gain-of-function of APP-Cu(I)
      complexes might result in a perturbation of free radical homeostasis. What
      significance such a perturbation may have for the pathogenesis of Alzheimer's
      disease remains to be determined.

PMID- 9585535
TI  - Proteolytic cleavage of urokinase-type plasminogen activator by stromelysin-1
      (MMP-3).
AB  - Matrix metalloproteinase-3 (MMP-3, or stromelysin-1) specifically hydrolyzes the
      Glu143-Leu144 peptide bond in 45-kDa single-chain urokinase-type plasminogen
      activator (scu-PA) and in its two-chain (tcu-PA) derivative, yielding a 17-kDa
      NH2-terminal domain comprising the u-PA receptor (u-PAR) binding site and a 32
      kDa COOH-terminal moiety containing the serine proteinase domain of u-PA. The
      conversion is completely abolished in the presence of the MMP inhibitors EDTA or
      1,10-phenanthroline. Biospecific interaction analysis indicates that binding of
      MMP-3 occurs through the 32-kDa fragment. The 32-kDa fragment derived from scu-PA
      (scu-PA-32k) has a specific activity of </=500 IU/mg, but it can be activated
      with plasmin to a two-chain derivative (tcu-PA-32k) with a specific activity of
      79 000 IU/mg. tcu-PA and tcu-PA-32k moieties derived from scu-PA-32k by plasmin
      or from tcu-PA by MMP-3 have comparable amidolytic activities toward the
      chromogenic substrate S-2444 (kcat/Km of 110 and 160 mM-1 s-1, respectively) and
      similar plasminogen activating activities in a coupled chromogenic substrate
      assay. Specific binding of the 17-kDa NH2-terminal domain to THP-1 monocytoid
      cells is completely abolished by competition with scu-PA but is not affected by
      scu-PA-32k (residual binding of 88 +/- 9% (mean +/- SEM; n = 3) with 25-fold
      molar excess). Thus, MMP-3 removes a functional NH2-terminal u-PAR-binding domain
      from u-PA without affecting its enzymatic properties.

PMID- 9585536
TI  - Biochemical characterization of the HIV-1 integrase 3'-processing activity and
      its inhibition by phosphorothioate oligonucleotides.
AB  - To better understand HIV-1 integrase (IN) functions, we determined the kinetic
      parameters of the 3'-processing reaction. Steady-state kinetic analysis performed
      using Dixon plots indicated that the concentration of active enzyme was 10-fold
      lower than that calculated by protein determination. The turnover number was low,
      suggesting that IN remained bound to DNA after cleavage. The catalytic efficiency
      increased 10-fold from 30 to 37 degrees C and 2-fold from 37 to 42 degrees C. In
      enzyme assays carried out at 37 degrees C, both single- and double-stranded
      phosphorothioate oligos bound to IN with an efficiency comparable to that of the
      phosphodiester duplex substrate. The competition efficiency of single-stranded
      oligos was directly related to the sequence length. On the other hand,
      phosphorothioate duplex U5 LTRs modified in the plus strand were capable of both
      competing with the substrate and directly inhibiting the 3'-processing activity.
      These results suggest that, in addition to other modes of action (inhibition of
      gp120-CD4 interaction and reverse transcriptase), phosphorothioate hetero- and
      homopolimeric oligos also potently inhibit the IN activity.

PMID- 9585537
TI  - Characterization of D10S and K71E mutants of human cytosolic hsp70.
AB  - To determine the effect of mutations at the nucleotide-binding site of
      recombinant Hsp70 on its interaction with protein and peptide substrates, point
      mutations were made at D10 and K71, two residues at the active site. The D10S
      mutation weakened both ATP and ADP binding, while the K71E mutation weakened only
      ATP binding. In binding experiments using Hsp70 with no bound nucleotide, the
      mutated Hsp70s interacted with clathrin and peptide just like the wild-type
      Hsp70. However, the D10 mutation completely abolished the effects of both ATP and
      ADP on peptide and clathrin binding. The K71 mutation also abolished the effect
      of ATP on substrate binding, but ADP, which still bound tightly, had its normal
      effect on substrate binding. In addition, the D10S and K71E mutants had greatly
      reduced ability to uncoat clathrin-coated vesicles at pH 7.0, bind to clathrin
      baskets at pH 6.0, and undergo polymerization induced by YDJ1 in the presence of
      ATP. We conclude, first, that nucleotides must bind strongly to Hsp70 to affect
      substrate binding and, second, that interaction of Hsp70 with DnaJ homologues may
      also require a strongly bound ATP.

PMID- 9585539
TI  - In vitro selected RNA molecules that bind to elongation factor Tu.
AB  - RNA molecules which bind to elongation factor Tu from T. thermophilus were
      isolated from a pool of ribooligonucleotides with a randomized sequence region.
      These RNAs interact with elongation factor Tu in both the GTP and the GDP form. A
      slight preference for the GTP form of the protein was observed. The isolated RNA
      aptamers compete with each other for a common binding site on elongation factor
      Tu. This binding site is different from the binding site for aminoacyl-tRNA or
      the binding site for elongation factor Ts and is located on domain II of
      elongation factor Tu. The selected RNAs do not bind to elongation factor G. The
      EF-Tu binding RNAs share a short consensus sequence, 5'-ACCGAAG-3', which was
      also found in the alpha-sarcin domain of T. thermophilus23S rRNA. The isolated
      RNAs have a hairpin structure with the 5'-ACCGAAG-3' sequence located in non-base
      paired regions. Chemical probing and deletion experiments indicate that the
      consensus sequence is required for the interaction with elongation factor Tu.

PMID- 9585538
TI  - Repressive effect on oligonucleosome transcription of the core histone tail
      domains.
AB  - Histone-DNA templates for bacteriophage T7 RNA polymerase were assembled from
      histone octamers and three different DNA species, two circular (pGEMEX-1 and
      pT207-18) and one linear (T7-207-18). pGEMEX is devoid of nucleosome positioning
      sequences, while in pT207-18 and T7-207-18 the region downstream of the promoter
      contains 18 tandem repeats of a 207 bp positioning sequence derived from the 5S
      RNA gene of the sea urchin Lytechinus variegatus. Elimination of the histone
      tails in the assembled oligonucleosomes by trypsin digestion is accompanied, in
      all three DNA species, by substantial increases in transcription efficiency,
      assayed at different KCl and MgCl2 concentrations, after allowing for the
      aggregation observed under certain conditions. In the absence of KCl and at low
      MgCl2 concentration, the presence of 2 mM spermidine causes substantial
      aggregation of the intact oligonucleosomes but has a much smaller effect on those
      trypsin digested. The untreated histone-DNA templates, assembled on pGEMEX-1 and
      T7-207-18, give transcription products significantly shorter than those obtained
      with the corresponding free DNA. With oligonucleosome templates lacking histone
      tails, the transcripts have an average length intermediate between those
      corresponding to free DNA and intact histone-DNA, which indicates a partial
      elimination of the elongation restrictions imposed by intact histone octamers.
      The absence of histone terminal domains facilitates both transcriptional
      initiation and elongation. Apparently, the interaction of the histone tails with
      DNA at the nucleosomal level is responsible, at least in part, for their
      repressive effect on transcription.

PMID- 9585540
TI  - Transfer RNA-pseudouridine synthetase Pus1 of Saccharomyces cerevisiae contains
      one atom of zinc essential for its native conformation and tRNA recognition.
AB  - RNA:pseudouridine synthetase (Pus1) from Saccharomyces cerevisiae is a multisite
      specific enzyme that catalyzes the formation of pseudouridine at positions 34 and
      36 of intron-containing precursor tRNAIle and at positions 27 and/or 28 of
      several yeast tRNAs. In this paper we demonstrate that the purified recombinant
      Pus1, expressed in Escherichia coli, contains one atom of zinc per 63-kDa
      monomer, as determined by atomic absorption spectroscopy. This zinc ion could not
      be removed by treatment with EDTA or urea. However, a zinc-depleted enzyme was
      obtained after prolonged dialysis against the specific chelating agent 1,10
      phenanthroline. Removal of the zinc ion resulted in inactivation of the enzyme
      with concomitant loss of its ability to bind tRNA. Dialysis of the zinc-depleted
      inactive enzyme against buffer containing zinc ions led to recovery of up to 25%
      of bound zinc in parallel with 25% of its initial activity. Removal of the
      tightly bound zinc atom resulted in a conformational change of the protein, as
      determined by analytical ultracentrifugation, with minor changes in the internal
      structure of the protein, as evidenced by circular dichroism and infrared and
      fluorescence spectroscopy. Our results are consistent with a structural role for
      the zinc in the tRNA-pseudouridine synthetase Pus1; zinc ion could maintain the
      association between domains structurally organized around the coordinated metal
      ion. Zinc chelation was never demonstrated for any of the tRNA-pseudouridine
      synthetases characterized so far.

PMID- 9585542
TI  - Modulation in kinetics of lactone ring hydrolysis of camptothecins upon
      interaction with topoisomerase I cleavage sites on DNA.
AB  - The kinetics of hydrolysis of the alpha-hydroxylactone ring of anticancer agents
      belonging to the camptothecin (CPT) series has been followed using their
      fluorescence emission. Data obtained for CPT, CPT-11, and SN-38, either in their
      free form or in the presence of DNA and/or topoisomerase I (top1), have been
      compared. DNA was modeled using three types of double-strand oligonucleotides
      corresponding to top1 cleavage site enhanced in the presence of the drug (olg1),
      top1 site independent of CPT (olg2), and nonspecific synthetic oligonucleotide
      containing only AT and no GC base pairs (olg3). Cleavage assays indicated the
      absence of top1-mediated cleavage on olg3, both in the presence and in the
      absence of CPT. The kinetics data also showed ratio-dependent stabilization of
      the lactone forms of CPTs when in the presence of an excess of olg1 or olg2, but
      not of olg3. These observations correlate with the previously reported
      preferential binding of CPTs to guanines. Although lactone hydrolysis was not
      perturbed by top1 alone, this enzyme hindered lactone stabilization by specific
      oligonucleotides. After addition of top1 to CPT-olg1 or CPT-olg2 complexes, the
      lactone ring of the drug was destabilized. No lactone stabilization was observed
      when olg1 was added to CPT-top1 complexes or when olg1-top1 complexes were added
      to CPT.

PMID- 9585541
TI  - Participation of the 3'-CCA of tRNA in the binding of catalytic Mg2+ ions by
      ribonuclease P.
AB  - Ribonuclease P (RNase P) contains a catalytic RNA that cleaves precursor tRNA
      (pre-tRNA) to form the mature 5'-end of tRNA. Previous kinetic analyses with
      mutant pre-tRNAs indicated that both C residues of the invariant 3'-terminal CCA
      form specific interactions with RNase P RNA that contribute to the energetics of
      substrate binding (1, 2). In the present study, we have used single-turnover
      kinetic analysis to investigate whether specific changes in the 3'-terminal CCA
      influence the rate of the chemical step through which enzyme-bound substrate is
      converted to product (k2). At optimal ionic strength (1.0 M NH4Cl, 25 mM MgCl2),
      deletion or substitution of the 3'-proximal C residue (CCA) reduced the rate of
      the chemical step of cleavage (k2) by 60-fold. Similar changes to the 5'-proximal
      C residue (CCA) or the 3'-terminal A residue (CCA) reduced k2 only a few fold.
      Each mutant substrate exhibited weakened affinity for Mg2+, as measured by Hill
      plots, and the severity of these defects correlated with the observed reductions
      in k2. Furthermore, elevated concentrations of Mg2+ partially, but not
      completely, suppress the k2 defects caused by deletion or substitution of the 3'
      proximal C residue. We conclude that the 3'-CCA of pre-tRNA, particularly the 3'
      proximal C residue, comprises part of the catalytic pocket formed in the pre-tRNA
      RNase P complex and participates in the binding of Mg2+ ions that are essential
      for catalysis by RNase P RNA.

PMID- 9585543
TI  - Pre-steady-state analysis of ATP hydrolysis by Saccharomyces cerevisiae DNA
      topoisomerase II. 1. A DNA-dependent burst in ATP hydrolysis.
AB  - When bound to DNA, topoisomerase II from Saccharomyces cerevisiae exhibits burst
      kinetics with respect to ATP hydrolysis. Pre-steady-state analysis shows that the
      enzyme binds and hydrolyzes two ATP per reaction cycle. Our data indicate that at
      least one of the two ATP is rapidly hydrolyzed prior to the rate-determining step
      in the reaction mechanism. When DNA is not bound to topoisomerase II, the rate
      determining step shifts to become either ATP binding or hydrolysis. Two possible
      mechanisms are proposed that agree with our observations.

PMID- 9585545
TI  - UTP is a cofactor for the DNA strand exchange reaction performed by the RecA
      protein of Escherichia coli.
AB  - The RecA protein of Escherichia coli is required for homologous genetic
      recombination and induction of the SOS regulon. In order for RecA protein to
      function in these two roles, a nucleoside triphosphate cofactor, usually ATP or
      dATP, is required. We have examined the ability of UTP to substitute for (r,d)ATP
      as nucleoside triphosphate cofactor. We have found that although UTP is
      hydrolyzed by RecA protein in the presence of long DNA molecules, it is not
      hydrolyzed in reactions in which the cofactors are oligodeoxyribonucleotides less
      than approximately 50 nt in length. We show that UTP can efficiently substitute
      for ATP as nucleoside triphosphate cofactor for the DNA strand exchange reaction
      in vitro. The RecA1332 protein (Cys129 --> Met), which was originally shown to be
      defective for homologous recombination in vivo, is able to perform DNA strand
      exchange in vitro with ATP, but is unable to do so with UTP. These results
      suggest that UTP may be a cofactor for DNA strand exchange in vivo. The inability
      of RecA protein to hydrolyze UTP with oligodeoxyribonucleotides as cofactor and
      the ability of RecA to utilize UTP as cofactor in DNA strand exchange suggest a
      separation of the functions of RecA protein into those that require exclusively
      ATP and those which can utilize additional nucleoside triphosphate cofactors.

PMID- 9585546
TI  - Thermodynamic consequences of an abasic lesion in duplex DNA are strongly
      dependent on base sequence.
AB  - The abasic site in DNA may arise spontaneously, as a result of nucleotide base
      damage, or as an intermediate in glycosylase-mediated DNA-repair pathways. It is
      the most common damage found in DNA. We have examined the consequences of this
      lesion and its sequence context on DNA duplex structure, as well as the thermal
      and thermodynamic stability of the duplex, including the energetic origins of
      that stability. To this end, we incorporated a tetrahydrofuran abasic site
      analogue into a family of 13-mer DNA duplexes, wherein the base opposite the
      lesion (A, C, G, or T) and the base pairs neighboring the lesion (C.G or G.C)
      were systematically varied and characterized by a combination of spectroscopic
      and calorimetric techniques. The resulting data allowed us to reach the following
      conclusions: (i) the presence of the lesion in all sequence contexts studied does
      not alter the global B-form conformation characteristic of the parent undamaged
      duplex; (ii) the presence of the lesion induces a significant enthalpic
      destabilization of the duplex, with the magnitude of this effect being dependent
      on the sequence context; (iii) the thermodynamic impact of the lesion is
      dominated by the identity of the neighboring base pairs, with the cross strand
      partner base exerting only a secondary thermodynamic effect on duplex properties.
      In the aggregate, our data reveal that even in the absence of lesion-induced
      alterations in global structure, the abasic lesion can significantly alter the
      thermodynamic properties of the host duplex, with the magnitude of this impact
      being strongly dependent on sequence context.

PMID- 9585544
TI  - Pre-steady-state analysis of ATP hydrolysis by Saccharomyces cerevisiae DNA
      topoisomerase II. 2. Kinetic mechanism for the sequential hydrolysis of two ATP.
AB  - In the preceding paper, we showed that DNA topoisomerase II from Saccharomyces
      cerevisiae binds two ATP and rapidly hydrolyzes at least one of them before
      encountering a slow step in the reaction mechanism. These data are potentially
      consistent with two different types of reaction pathways: (1) sequential ATP
      hydrolysis or (2) simultaneous hydrolysis of both ATP. Here, we present results
      that are consistent only with topoisomerase II hydrolyzing its two bound ATP
      sequentially. Additionally, these results indicate that the products of the first
      hydrolysis are released from the enzyme before the second ATP is hydrolyzed.
      Release of products from both the first and second hydrolyses contributes to the
      rate-determining process. The proposed mechanism for ATP hydrolysis by
      topoisomerase II is complex, having nine rate constants. To calculate values for
      each of these rate constants, a technique of kinetic parameter estimation was
      developed. This technique involved using singular perturbation theory in order to
      estimate rate constants, and consequently identify kinetic steps following the
      rate-determining step.

PMID- 9585547
TI  - Chimeric beta-EF3-alpha hemoglobin (Psi): energetics of subunit interaction and
      ligand binding.
AB  - Among the numerous strategies to design an oxygen carrier, we outline in this
      work the engineering of a stable homotetrameric hemoglobin, expressed in
      Escherichia coli. The chimeric globin (Psi) consists of the first 79 residues of
      human beta globin (corresponding to positions NA1 --> EF3) followed by the final
      67 residues of human alpha globin (corresponding to positions EF3 --> HC3). The
      molecular mass for beta-EF3-alpha (Psi) globin was measured using mass
      spectrometry to be equal to its theoretical value: 15782 Da. Correct protein
      folding was assessed by UV/visible and fluorescence spectra. The subunit
      interaction free energies were estimated by HPLC gel filtration. In the
      cyanometHb species, the formation of the dimer-tetramer interface is 2 kcal/mol
      less favorable (Delta G = -7 kcal/mol) than that of Hb A (Delta G = -9 kcal/mol),
      whereas the dimer-monomer interface is tightly assembled (< -10 kcal/mol) as for
      the Hb A alpha 1 beta 1 interface. In contrast to Hb A, oxygen binding to Psi Hb
      is not cooperative. The free energy for binding four oxygen molecules to a Psi
      homotetramer is slightly increased compared to a Hb A heterotetramer (-28 and 
      27.5 kcal/4 mol of O2, respectively). The intrinsic O2 affinity of a Psi
      homodimer is 6-fold higher than that of a homotetramer. The linkage scheme
      between dimer-tetramer subunit assembly and the noncooperative oxygenation of Psi
      Hb predicts a stabilization of the tetramer after ligand release. This protein
      mechanism resembles that of Hb A for which the dimers exhibit a 100-fold higher
      O2 affinity relative to deoxy tetramers (which are 10(5) times more stable than
      oxy tetramers). A potent allosteric effector of Hb A, RSR4, binds to Psi Hb
      tetramers, inducing a decrease of the overall O2 affinity. Since RSR4 interacts
      specifically with two binding sites of deoxy Hb A, we propose that the chimeric
      tetramer folding is close to this native structure.

PMID- 9585548
TI  - Structure and orientation of the oxygen-evolving manganese complex of green algae
      and higher plants investigated by X-ray absorption linear dichroism spectroscopy
      on oriented photosystem II membrane particles.
AB  - X-ray absorption spectroscopy at the Mn K-edge has been performed on multilayers
      of photosystem II-enriched fragments of the native thylakoid membrane prepared
      from a higher plant (spinach) and a unicellular green alga (Scenedesmus
      obliquus). Spectra collected for various angles between the prevailing
      orientation of the thylakoid membrane normal and the X-ray electric field vector
      contain information on the atomic structure of the tetranuclear manganese complex
      of photosystem II (PS II) and its orientation with respect to the membrane
      normal. The previously used approach for evaluation of the dichroism of extended
      X-ray absorption fine structure (EXAFS) spectra [George, G. N., et al. (1989)
      Science 243, 789-791] is modified, and the following results are obtained for PS
      II in its dark-stable state (S1-state): (1) structure and orientation of the PS
      II manganese complexes of green algae and higher plants are highly similiar or
      fully identical; (2) two 2.7-A vectors, which, most likely, connect the Mn nuclei
      of a planar Mn2(mu-O2) structure, are at an average angle of 80 degrees +/- 10
      degrees with respect to the thylakoid normal; (3) the plane of the Mn2(mu-O2)
      structures is rather in parallel with the thylakoid plane than perpendicular.
      Structural models for the oxygen-evolving manganese complex and its orientation
      in the thylakoid membrane are discussed within the context of the presented
      results.

PMID- 9585550
TI  - Molybdenum cofactor properties and [Fe-S] cluster coordination in Escherichia
      coli nitrate reductase A: investigation by site-directed mutagenesis of the
      conserved his-50 residue in the NarG subunit.
AB  - Most of the molybdoenzymes contain, in the amino-terminal region of their
      catalytic subunits, a conserved Cys group that in some cases binds an [Fe-S]
      cluster. In dissimilatory nitrate reductases, the first Cys residue of this motif
      is replaced by a conserved His residue. Site-directed mutagenesis of this residue
      (His-50) was performed on the NarG subunit from Escherichia coli nitrate
      reductase A. The results obtained by EPR spectroscopy enable us to exclude the
      implication of this residue in [Fe-S] binding. Additionally, we showed that the
      His-50 residue does not coordinate the molybdenum atom, but its substitution by
      Cys or Ser introduces a perturbation of the hydrogen bonding network around the
      molybdenum cofactor. From potentiometric studies, it is proposed that the high-pH
      and the low-pH forms of the Mo(V) are both involved during the redox turnover of
      the enzyme. Perturbation of the Mo(V) pKV value might be responsible for the low
      activity reported in the His-50-Cys mutant enzyme. A catalytic model is proposed
      in which the protonation/deprotonation of the Mo(V) species is an essential step.
      Thus, one of the two protons involved in the catalytic cycle could be the one
      coupled to the molybdenum atom in the dissimilatory nitrate reductase of E. coli.

PMID- 9585549
TI  - Effect of iron-sulfur cluster environment in modulating the thermodynamic
      properties and biological function of ferredoxin from Pyrococcus furiosus.
AB  - The ferredoxin (7.5 kDa) of the hyperthermophilic archaeon, Pyrococcus furiosus,
      contains a single [4Fe-4S]1+,2+ cluster that is coordinated by three Cys and one
      Asp residue rather than the expected four Cys. The role of this Asp residue was
      investigated using a series of mutants, D14X, where X = C, S, H, N, V, and Y,
      prepared by heterologous gene expression in Escherichia coli. While the
      recombinant form of the wild-type and the D14S and D14C mutants contained a [4Fe
      4S]1+,2+ cluster, the D14V, D14H, D14Y, and D14N proteins contained a [3Fe-4S]0,+
      center, as determined by visible spectroscopy and electrochemistry. The redox
      potentials (at pH 7.0, 23 degrees C) of the D14C and D14S mutants were decreased
      by 58 and 133 mV, respectively, compared to those of the wild-type 4Fe-ferredoxin
      (Em -368 mV), while those of the 3Fe-protein mutants (including the 3Fe-form of
      the D14S, generated by chemical oxidation) were between 15 and 118 mV more
      positive than that of wild-type 3Fe-form (obtained by chemical oxidation, Em -203
      mV). The reduction potentials of all of the 3Fe-forms, except the D14S mutant,
      showed a pH response over the range 3.0-10.0 with a pK of 3.3-4.7, and this was
      assigned to cluster protonation. The D14H mutant and the wild-type 3Fe-proteins
      showed an additional pK (both at 5.9) assumed to arise from protonation of the
      amino acid side chain. With the 4Fe-proteins, there was no dramatic change in the
      potentials of the wild-type or D14C form, while the pH response of the D14S
      mutant (pK 4.75) was ascribed to protonation of the serinate. While the
      ferredoxin variants exhibited a range of thermal stabilities (measured at 80
      degrees C, pH 2.5), none of them showed any temperature-dependent transitions (0
      80 degrees C) in their reduction potentials, and there was no correlation between
      the calculated DeltaS degrees' values and the absorbance maximum, reduction
      potential, or hydrophobicity of residue 14. In contrast, there was a linear
      correlation between the DeltaH degrees' value and reduction potential. Kinetic
      analyses were carried out at 80 degrees C using the ferredoxin as either an
      electron acceptor to pyruvate oxidoreductase (POR) or as an electron donor to
      ferredoxin:NADP oxidoreductase (FNOR, both from P. furiosus). The data showed
      that the reduction potential of the ferredoxin, rather than cluster type or the
      nature of the residue at position 14, appears to be the predominant factor in
      determining efficiency of electron transfer in both systems. However, compared to
      all the variants, the reduction potential of WT Fd makes it the most appropriate
      protein to both accept electrons from POR and donate them to FNOR.

PMID- 9585551
TI  - Site-directed mutagenesis of Phe 97 to Glu in amicyanin alters the electronic
      coupling for interprotein electron transfer from quinol methylamine
      dehydrogenase.
AB  - Conversion by site-directed mutagenesis of Phe 97 of amicyanin to Glu
      significantly decreases the rate constant for the electron-transfer reaction from
      the quinol form of methylamine dehydrogenase to amicyanin. It is shown that the
      DeltaG degrees and reorganizational energy (lambda) associated with the electron
      transfer reaction are unaffected by the mutation and that the decrease in the
      electron-transfer rate is attributable completely to a decrease in the electronic
      coupling matrix element (HAB). Phe 97 is not a part of the predicted pathway for
      electron-transfer from the tryptophan tryptophylquinone cofactor of MADH to the
      copper of amicyanin. The most likely explanation for these results is that the
      mutation of this residue at the protein-protein interface causes an increase in
      the interprotein distance within the protein complex. The change in distance
      necessary to cause the observed reduction of HAB is calculated assuming a range
      of beta values, and assuming either solely a direct distance dependence or a
      pathway dependence, for the long-range electron-transfer reaction. Thermodynamic
      analysis of the association constants for complex formation reveal that the
      reaction with the mutant amicyanin exhibits a large positive change in heat
      capacity whereas this is not observed in the reaction with the wild-type. This
      may be explained by the replacement of a hydrophobic residue with a polar residue
      at what is normally a hydrophobic protein-protein interface. The impact of these
      results on possible explanations for the relatively large reorganizational energy
      associated with this interprotein electron-transfer reaction is also discussed.

PMID- 9585552
TI  - Understanding the electronic properties of the CuA site from the soluble domain
      of cytochrome c oxidase through paramagnetic 1H NMR.
AB  - The soluble domain of the subunit II of cytochrome c oxidase from Paracoccus
      versutus was cloned, expressed, and studied by 1H NMR at 600 MHz. The properties
      of the redox-active dinuclear CuA site in the paramagnetic mixed-valence Cu(I)
      Cu(II) state were investigated in detail. A group of relatively sharp signals
      found between 30 and 15 ppm in the 1H NMR spectrum correspond to the imidazole
      protons of the coordinated histidines (H181 and H224). A second group of broader
      and farther shifted signals between 50 and 300 ppm are assigned to Hbeta protons
      of the bridging cysteines (C216 and C220); the protons from the weak M227 and
      E218 ligands do not shift outside of the diamagnetic envelope. About 40% of the
      total spin density appears delocalized over the cysteine-bridging ligands while a
      much smaller amount is delocalized on the two ligand histidines. The latter have
      similar spin density distributions. Analysis of the pattern of the hyperfine
      shifts of the Cys H beta protons shows that the ground state bears 2B3u
      character, in which the sulfur lobes in the singly occupied molecular orbital are
      aligned with the Cu-Cu axis. Analysis of the temperature dependence of the shifts
      of the Cys H beta signals leads to the conclusion that the 2B2u excited state is
      thermally accessible at room temperature (Delta E approximately kT).

PMID- 9585553
TI  - Involvement of glutamic acid 278 in the redox reaction of the cytochrome c
      oxidase from Paracoccus denitrificans investigated by FTIR spectroscopy.
AB  - The molecular processes concomitant with the redox reactions of wild-type and
      mutant cytochrome c oxidase from Paracoccus denitrificans were analyzed by a
      combination of protein electrochemistry and Fourier transform infrared (FTIR)
      difference spectroscopy. Oxidized-minus-reduced FTIR difference spectra in the
      mid-infrared (4000-1000 cm-1) reflecting full or stepwise oxidation and reduction
      of the respective cofactor(s) were obtained. In the 1800-1000 cm-1 range, these
      FTIR difference spectra reflect changes of the polypeptide backbone geometry in
      the amide I (ca. 1620-1680 cm-1) and amide II (ca. 1560-1540 cm-1) region in
      response to the redox transition of the cofactor(s). In addition, several modes
      in the 1600-1200 cm-1 range can be tentatively attributed to heme modes. A peak
      at 1746 cm-1 associated with the oxidized form and a peak at 1734 cm-1 associated
      with the reduced form were previously discussed by us as proton transfer between
      Asp or Glu side chain modes in the course of the redox reaction of the enzyme
      [Hellwig, P., Rost, B., Kaiser, U., Ostermeier, C., Michel, H., and Mantele, W.
      (1996) FEBS Lett. 385, 53-57]. These signals were resolved into several
      components associated with the oxidation of different cofactors. For a stepwise
      potential titration from the fully reduced state (-0.5 V) to the fully oxidized
      state (+0.5 V), a small component at 1738 cm-1 develops in the potential range of
      approximately +0.15 V and disappears at more positive potentials while the main
      component at 1746 cm-1 appears in the range of approximately +0.20 V (all
      potentials quoted vs Ag/AgCl/3 M KCl). This observation clearly indicates two
      different ionizable residues involved in redox-induced proton transfer. The major
      component at 1746 cm-1 is completely lost in the FTIR difference spectra of the
      Glu 278 Gln mutant enzyme. In the spectrum of the subunit I Glu 278 Asp mutant
      enzyme, the major component of the discussed difference band is lost. In
      contrast, the complete difference signal of the wild-type enzyme is preserved in
      the Asp 124 Asn, Asp 124 Ser, and Asp 399 Asn variants, which are critical
      residues in the discussed proton pump channel as suggested from structure and
      mutagenesis experiments. On the basis of these difference spectra of mutants, we
      present further evidence that glutamic acid 278 in subunit I is a crucial residue
      for the redox reaction. Potential titrations performed simultaneously for the IR
      and for the UV/VIS indicate that the signal related to Glu 278 is coupled to the
      electron transfer to/from heme a; however, additional involvement of CuB electron
      transfer cannot be excluded.

PMID- 9585554
TI  - Redox dependent changes at the heme propionates in cytochrome c oxidase from
      Paracoccus denitrificans: direct evidence from FTIR difference spectroscopy in
      combination with heme propionate 13C labeling.
AB  - Specific isotope labeling at the carboxyl groups of the four heme propionates of
      cytochrome c oxidase from Paracoccus denitrificans was used in order to assign
      signals observed in electrochemically induced redox Fourier transform infrared
      (FTIR) difference spectra of this enzyme. For this purpose, the hemA gene of the
      P. denitrificans strain PD1222, coding for 5-aminolevulinate synthase, was
      deleted by partial replacement with a kanamycin resistance cartridge, resulting
      in a stable 5-aminolevulinic acid (ALA) auxotrophy. Normal growth of this
      deficient strain and cytochrome c oxidase yield comparable to that of P.
      dentrificans wild-type strain PD1222 could be obtained by supplementation with
      0.1 mM ALA in the growth medium. Visible spectra and reduced-minus-oxidized FTIR
      spectra showed that the purified cytochrome c oxidase had spectral
      characteristics identical to those of the wild-type enzyme. The decrease of a
      negative signal at 1676 cm-1 in the reduced-minus-oxidized FTIR difference
      spectra of the 13C-labeled cytochrome c oxidase in comparison to those of the
      unlabeled protein allowed the assignment of this signal to a COOH vibration mode
      of at least one of the four heme propionates. Moreover, a negative band at
      approximately 1570 cm-1 shifted to smaller wavenumbers in the spectra of the 13C
      labeled enzyme in comparison to the spectra of the unlabeled enzyme and was thus
      assigned to contributions from an antisymmetric COO- mode of one or more of the
      four heme propionates. Additionally, a positive signal at 1538 cm-1 shifted to
      approximately 1500 cm-1 in the spectra of the isotopically labeled protein and
      was therefore assigned to at least one antisymmetric COO- mode of the heme
      propionates. A negative signal at 1390 cm-1, which has been shifted to 1360 cm-1
      in the spectra of the 13C-labeled enzyme, is due to a symmetric COO- mode from at
      least one heme propionate. These results suggest that at least two of the four
      heme propionates in cytochrome c oxidase undergo significant vibrational changes
      upon reduction of the enzyme, either by protonation/deprotonation or by
      environmental changes.

PMID- 9585556
TI  - Kinetic analysis by fluorescence of the interaction between Ras and the catalytic
      domain of the guanine nucleotide exchange factor Cdc25Mm.
AB  - Guanine nucleotide exchange factors (GEFs) activate Ras proteins by stimulating
      the exchange of GTP for GDP in a multistep mechanism which involves binary and
      ternary complexes between Ras, guanine nucleotide, and GEF. We present
      fluorescence measurements to define the kinetic constants that characterize the
      interactions between Ras, GEF, and nucleotides, similar to the characterization
      of the action of RCC1 on Ran [Klebe et al. (1995) Biochemistry 34, 12543-12552].
      The dissociation constant for the binary complex between nucleotide-free Ras and
      the catalytic domain of mouse Cdc25, Cdc25(Mm285), was 4.6 nM, i.e., a 500-fold
      lower affinity than the Ras.GDP interaction. The affinities defining the ternary
      complex Ras. nucleotide.Cdc25(Mm285) are several orders of magnitude lower. The
      maximum acceleration by Cdc25(Mm285) of the GDP dissociation from Ras was more
      than 10(5)-fold. Kinetic measurements of the association of nucleotide to
      nucleotide-free Ras and to the binary complex Ras. Cdc25(Mm285) show that these
      reactions are practically identical: a fast binding step is followed by a
      reaction of the first order which becomes rate limiting at high nucleotide
      concentrations. The second reaction is thought to be a conformational change from
      a low- to a high-affinity nucleotide binding conformation in Ras. Taking into
      consideration all experimental data, the reverse isomerization reaction from a
      high- to a low-affinity binding conformation in the ternary complex Ras.
      GDP.Cdc25(Mm285) is postulated to be the rate-limiting step of the GEF-catalyzed
      exchange. Furthermore, we demonstrate that the disruption of the Mg2+-binding
      site is not the only factor in the mechanism of GEF-catalyzed nucleotide exchange
      on Ras.

PMID- 9585555
TI  - Mechanism-based inactivation of human cytochrome P450 1A2 by furafylline:
      detection of a 1:1 adduct to protein and evidence for the formation of a novel
      imidazomethide intermediate.
AB  - The rapid loss of human CYP1A2 (cytochrome P450 1A2) activity caused by the 8
      methylxanthine furafylline is investigated with the aim of determining whether a
      stable covalent adduct of the xanthine to the enzyme could be identified.
      Metabolic studies employing expressed CYP1A2 with radiolabeled furafylline and a
      close analogue, cyclohexylline, where the furan ring is replaced with
      cyclohexane, indicate that these xanthines are bound in a 1:1 ratio to CYP1A2
      protein. This result, combined with earlier kinetic studies, verifies that these
      compounds are mechanism-based inhibitors of the enzyme. The 8'-methyl carbinols
      are the only metabolites formed by CYP1A2, and substantial (70-80%) incorporation
      of oxygen from the medium into the carbinols is observed. Carbinol formation is
      further characterized by high intramolecular isotope effects (kH/kD > 9) and low
      intermolecular isotope effects (DV/K < 2). Overall partition ratios are low (5.0
      and 7.6, respectively), confirming our previous conclusion that furafylline is an
      efficient inactivator. By contrast, the N7-methyl-8-methylxanthines are good
      substrates for CYP1A2 but are not themselves inactivating agents. In addition to
      other metabolic products, the 8'-methyl carbinols of these N7-methyl-8
      methylxanthines are formed in substantial amounts with equally high
      intramolecular isotope effects; however, the carbinol oxygen is derived
      exclusively from molecular oxygen. We conclude that oxidation of the 8-methyl
      group of furafylline and cyclohexylline, but not their N7-methyl analogues, by
      CYP1A2 promotes a major fraction of the inactivating xanthines to a two electron
      oxidized intermediate which either terminates enzyme activity by reaction with an
      active site amino acid or is decomposed by reaction with the medium to give
      carbinol.

PMID- 9585557
TI  - Thermodynamics of the interaction of the Escherichia coli regulatory protein TyrR
      with DNA studied by fluorescence spectroscopy.
AB  - Fluorescence quenching was used to study the site-specific binding of the
      Escherichia coli regulatory protein TyrR to a fluoresceinated oligonucleotide
      (9F30A/30B) containing a TyrR binding site. The equilibrium constant for the
      interaction (KL) was measured as a function of temperature and salt concentration
      in the presence and absence of ATPgammaS, a specific ligand for TyrR.
      Fluorescence titrations yielded a KL value of 1.20 x 10(7) M-1 at 20 degrees C,
      which was independent of the acceptor (9F30A/30B) concentration in the range 5
      500 nM, indicating that the system exhibits true equilibrium binding. Clarke and
      Glew analysis of the temperature dependence of binding revealed a linear
      dependence of R ln KL on temperature in the absence of ATPgammaS. The
      thermodynamic parameters obtained at 20 degrees C (theta) were = -35.73 kJ mol-1,
      = 57.41 kJ mol-1, and = 93.14 kJ mol-1. Saturating levels of ATPgammaS (200
      microM) strengthened binding at all temperatures and resulted in a nonlinear
      dependence of Rln KL on temperature. The thermodynamic parameters characterizing
      binding under these conditions were = -39.32 kJ mol-1, = 37.16 kJ mol-1, = 76.40
      kJ mol-1, and = -1.03 kJ mol-1 K-1. Several conclusions were drawn from these
      data. First, binding is entropically driven at 20 degrees C in both the presence
      and absence of ATPgammaS. This can partly be accounted for by counterions
      released from the DNA upon TyrR binding; in the absence of ATPgammaS and divalent
      cations, the TyrR-9F30A/30B interaction results in the release of two to three
      potassium ions. Second, the more favorable value, and hence tighter binding
      observed in the presence of ATPgammaS, is primarily due to a decrease in (-20.3
      kJ mol-1), which overcomes an unfavorable decrease in (-16.7 kJ mol-1). Third,
      the negative value obtained in the presence of ATPgammaS indicates that the
      binding of ATPgammaS favors a conformational change in TyrR upon binding to
      9F30A/30B, yielding a more stable complex.

PMID- 9585558
TI  - Steady state and time-resolved fluorescence study of residual structures in an
      unfolded form of yeast phosphoglycerate kinase.
AB  - A previous study performed using steady state fluorescence has revealed the
      existence of residual structures surrounding the two tryptophan residues in an
      unfolded form of yeast phosphoglycerate kinase [Garcia, P., et al. (1995)
      Biochemistry 34, 397-404]. In this paper, we present a more detailed
      characterization of these residual structures, through the study of two single
      tryptophan-containing mutants of yPGK, W333F and W308Y. Denaturation experiments
      have first been performed at low temperatures to assess the nature of the
      interactions stabilizing these residual structures. On the other hand, the
      compactness and dynamics of the protein matrix were probed using tryptophan
      fluorescence quenching by acrylamide at various denaturant concentrations. Taking
      into consideration the changes in sample viscosity induced by addition of
      guanidinium chloride made feasible the use of this technique during the
      denaturation process. These different approaches have shown that the residual
      structures around tryptophan 308 are mainly stabilized by hydrophobic
      interactions and are more compact and less fluctuant than the ones surrounding
      tryptophan 333. Native and denatured yPGK have also been studied by time-resolved
      fluorescence spectroscopy. In the native protein, tryptophan buried in the core,
      W333, is mainly associated with a lifetime close to 0.1 ns, whereas tryptophan
      that is partially accessible to the solvent, W308, has a lifetime close to 0. 5
      ns. The time-resolved tryptophan fluorescence emission of wild-type yPGK can be
      accounted for quantitatively by the summed emissions of its two single tryptophan
      mutants. The significance of minor long lifetime components is discussed for the
      two tryptophan residues. This new assignment of fluorescent decay times has
      allowed for the detection of a folding intermediate in which the environment of
      tryptophan 333 is modified for denaturant concentrations lower than those for
      tryptophan 308.

PMID- 9585559
TI  - Structural replacement of active site monovalent cations by the epsilon-amino
      group of lysine in the ATPase fragment of bovine Hsc70.
AB  - We have assessed the ability of the epsilon-amino group of a non-native lysine
      chain to substitute for a monovalent cation in an enzyme active site. In the
      bovine Hsc70 ATPase fragment, mutation of cysteine 17 or aspartic acid 206 to
      lysine potentially allows the replacement of an active site potassium ion with
      the epsilon-amino nitrogen. We examined the ATP hydrolysis kinetics and crystal
      structures of isolated mutant ATPase domains. The introduced epsilon-amino
      nitrogen in the C17K mutant occupies a significantly different position than the
      potassium ion. The introduced epsilon-amino nitrogen in the D206K mutant occupies
      a position indistinguishable from that of the potassium in the wild-type
      structure. Each mutant retains <5% ATPase activity when compared to the wild type
      under physiological conditions (potassium buffer) although substrate binding is
      tighter, probably as a consequence of slower release. It is possible to construct
      a very good structural mimic of bound cation which suffices for substrate binding
      but not for catalytic activity.

PMID- 9585561
TI  - Physicochemical and biochemical properties of 2',5'-linked RNA and 2',5'
      RNA:3',5'-RNA "hybrid" duplexes.
AB  - In recent publications, oligonucleotides joined by 2',5'-linkages were found to
      bind to complementary single-stranded RNA but to bind weakly, or not at all, to
      single-stranded DNA [e.g., P. A. Giannaris and M. J. Damha (1993) Nucleic Acids
      Res. 21, 4742-4749]. In this work, the biochemical and physicochemical properties
      of 2',5'-linked oligoribonucleotides containing mixed sequences of the four
      nucleobases (A, G, C, and U) were evaluated. CD spectra of RNA:2', 5'-RNA
      duplexes were compared with the spectra of DNA:DNA, RNA:RNA, and DNA:RNA duplexes
      of the same base sequence. The CD results indicated that the RNA:2',5'-RNA duplex
      structure more closely resembles the structure of the RNA:DNA hybrid, being more
      A-form than B-form in character. The melting temperature (Tm) values of the
      backbone-modified duplexes were compared with the Tm values of the unmodified
      duplexes. The order of thermal stability was RNA:RNA > DNA:DNA approximately
      RNA:DNA approximately DNA:RNA > RNA:2',5'-RNA > 2',5'-RNA:2',5'-RNA >> DNA:2',5'
      RNA (undetected). RNA:2',5'-RNA duplexes are not substrates of the enzyme RNase H
      (Escherichia coli, or HIV-1 reverse transcriptase), but they can inhibit the
      RNase H-mediated cleavage of a natural DNA:RNA substrate. Structural models that
      are consistent with the selective association properties of 2',5'-linked
      oligonucleotides are discussed.

PMID- 9585560
TI  - Circular dichroism and electron microscopy of a core Y61F mutant of the F1 gene 5
      single-stranded DNA-binding protein and theoretical analysis of CD spectra of
      four Tyr --> Phe substitutions.
AB  - A core Y61F mutant of the gene 5 single-stranded DNA-binding protein (g5p) of f1
      bacterial virus aggregated when expressed from a plasmid, but, after refolding in
      vitro, it behaved much like wild-type and may be a stability or folding mutant.
      Circular dichroism (CD) titrations showed the same cooperative polynucleotide
      binding modes for Y61F and wild-type g5p. There are n = 4 and n congruent with
      2.5 modes for binding to poly[d(A)] at low ionic strengths, but n = 4, n = 3, and
      n congruent with 2-2.5 modes for binding to fd single-stranded viral DNA (fd
      ssDNA), where n is the number of nucleotides occluded by each bound g5p monomer
      in a given mode. Y61F g5p has slightly reduced affinity in the n = 4 mode.
      Electron microscopy showed that Y61F g5p forms left-handed nucleoprotein
      superhelices indistinguishable from wild-type. Progression from binding to fd
      ssDNA in the n = 4 to n = 3 to n congruent with 2-2.5 mode is accompanied by an
      increase in the number of helical turns, an increase from (7.7 +/- 0.3) to (9.5
      +/- 0.3) to ( approximately 10-13) g5p dimers per turn, and a decrease in the
      number of DNA nucleotides per turn. From CD spectra for four of five possible Y -
      > F g5p mutants, we infer that the fifth tyrosine, Tyr 56, contributes strongly
      to the CD. Retention of a strong 229 nm CD band in all mutants indicates that all
      retain elements of the native structure. Spectra of Y26F, Y34F, and Y61F g5p
      imply limited mobility of the replacement Phe. Comparison of measured with
      calculated CD spectra also suggests limited mobility for Tyr 26 and Tyr 34 in g5p
      in solution, and provides new information that the g5p structure in solution may
      be dominated by Tyr 41 rotamers differing from that stabilized in the crystal.

PMID- 9585562
TI  - Studying receptor-ligand interactions using encoded amino acid scanning.
AB  - A novel technique is described that allows the synthesis, functional analysis,
      and quantitative readout of defined arrays of polypeptide analogues in aqueous
      solution. Key to this approach is the use of a simple encoding-decoding system in
      which a unique Fmoc-amino acid tag is covalently attached to the C terminus of
      each member of a molecular array through a selectively cleavable bond. These tags
      can be cleanly removed from the molecules they encode, allowing single-step
      characterization and quantification of the entire mixture by HPLC. The utility of
      this technique is illustrated through the preparation of an array of proline-rich
      sequences based on the exchange factor C3G, one of the natural ligands of the N
      terminal SH3 domain from the proto-oncogene, c-Crk. The array was designed to
      systematically modify those residues within the C3G peptide ligand thought to
      make key interactions with the c-Crk SH3 domain. Using competition binding
      experiments, it was possible to determine the relative ED50 values for the entire
      array of molecules simultaneously. These studies revealed that in order to
      maintain optimal binding to the SH3 domain, the P-3 side chain of the ligand must
      be positively charged and the P-0 side chain must be hydrophobic and extend
      beyond the gamma-carbon. The excellent correlation between these relative ED50
      values and a series of relative Kd values determined from individual peptides
      suggests that this approach may be useful in determining, in a parallel fashion,
      the relative biological activities of arrays of polypeptides.

PMID- 9585563
TI  - Probe transfer with and without membrane fusion in a fluorescence fusion assay.
AB  - An analysis of the R18 fusion assay was made during the fusion of the Sendai
      virus with erythrocyte ghosts. The increase in R18 fluorescence, reflecting the
      interaction process, was evaluated in terms of the different processes that in
      principle may contribute to this increase, that is, monomeric probe transfer,
      hemifusion, and complete fusion. To this end, the kinetics of the R18-labeled
      lipid mixing were compared to those obtained with an assay in which the fusion
      monitoring probe, eosin-maleimide, was attached to the viral surface proteins.
      The experiments relied on the use of native and fusion-inactive viruses and
      studies involving viral and target membranes that were modified by the
      incorporation of the lysophospholipid. The total dequenching signal detected in
      the R18 assay consists of components from probe transferred without fusion and
      from fusion itself. At 37 degrees C, the initial rate of dequenching (within two
      minutes) was predominately from the probe diluted by fusion with little
      contribution from transfer. The dequenching signal due to the probe transfer
      without fusion occurred at temperatures as low as 10 degrees C and increased
      linearly with time. Complete fusion started at about 20-25 degrees C and
      increased sharply at 30 degrees C. The extent of hemifusion was deduced from the
      total R18 dequenching data and those of the eosin-maleimide labeled protein
      dilution method for the limiting cases; the analysis indicates that hemifusion
      started at about 15 degrees C and increased over the range 20-25 degrees C. The
      initial rate of dequenching of the R18 assay measured within 2 min gives an
      accurate measure of membrane fusion above 30 degrees C.

PMID- 9585564
TI  - The EGF receptor transmembrane domain: 2H NMR study of peptide phosphorylation
      effects in a bilayer environment.
AB  - Phosphorylation events are considered to be key control points in receptor
      tyrosine kinase function. We have used wide-line 2H NMR spectroscopy to look for
      physical effects of phosphorylating a threonine residue within the cytoplasmic
      domain of the human EGF receptor, as sensed at a distant site in the
      transmembrane portion. Modifications were made to Thr654 (a cytoplasmic residue
      suggested to be involved in regulation of EGF binding and of cytoplasmic domain
      function), and effects were sought at Ala623 (near the extracellular membrane
      surface but within the membrane-spanning region). The study was carried out on
      synthetic peptides corresponding to the EGF receptor transmembrane domain plus 10
      or 11 residues of the cytoplasmic domain, assembled into lipid bilayer membranes.
      Three peptides were compared that differed only at Thr654. This residue was
      alternately: nonphosphorylated but left as a (-)-charged C-terminus (-Thr654COO
      ), nonphosphorylated and with a neighboring amidated glycine residue as the C
      terminus (-Thr654GlyCONH2), or phosphorylated and with a neighboring amidated
      glycine residue as the C-terminus (-Thr654PO4-GlyCONH2). Bilayer membranes were
      composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) or 2:1
      POPC/cholesterol, containing 6 mol % peptide relative to phospholipid. The
      deuterated site, Ala623, was intrinsically conformationally sensitive; yet
      spatial orientation and motional order of the probe location were found not to be
      obviously influenced by phosphorylation.

PMID- 9585565
TI  - Domain swapping between Na,K- and H,K-ATPase identifies regions that specify Na,K
      ATPase activity.
AB  - We have used expression of chimeras between the structurally related Na,K- and
      H,K-ATPase alpha subunits to localize regions that determine Na,K-ATPase
      activity. Segments of the rat Na,K-ATPase alpha1 subunit were replaced by the
      corresponding portions of the rat gastric H,K-ATPase alpha subunit, and the
      constructs were transfected into ouabain-sensitive human HEK 293 cells. Using the
      ability to transfer ouabain resistance as a measure of sodium pump activity, we
      identified segments within the sodium pump that could be replaced with proton
      pump sequences without the loss of biological activity. These functionally
      interchangeable segments encompassed approximately 75% of the amino acid
      differences between the two transporters. Segments that could not be exchanged
      mapped to three discrete regions. One region spans residues 63-117 and includes
      the first transmembrane (TM) segment and a portion of the amino-terminal
      cytoplasmic domain. The second, from residue 320 to residue 413, encompasses TM 4
      and a portion of the third cytoplasmic domain, while the third region
      (encompassing residues 735-861 and 898-953) includes several TM domains in the
      carboxyl-terminal portion of the ATPase. Our results suggest that functional
      differences between Na,K- and H,K-ATPase, including differences in ion transport
      specificity, are likely to reside within these noninterchangeable segments.

PMID- 9585566
TI  - Loop I can modulate ADP affinity, ATPase activity, and motility of different
      scallop myosins. Transient kinetic analysis of S1 isoforms.
AB  - The striated muscle myosin of Placopecten moves actin faster in in vitro motility
      assays and has a higher actin-activated ATPase turnover rate than the myosin of
      the catch muscle. The heavy chain sequences of the two PlacoS1s are almost
      identical except at the surface loop 1 near the nucleotide binding pocket, where
      the two sequences vary significantly. Argopecten striated muscle myosin is 96%
      identical to Placopecten striated myosin, and both move actin with a similar
      velocity. To identify the individual kinetic steps which differ between these
      myosins, we completed a transient kinetic characterization of the three myosin
      S1s. The two striated S1s have similar rates of nucleotide binding to S1 and to
      acto.S1. The largest differences between the two are in the rate of ADP
      dissociation from S1 and affinity of ADP to S1, which differ by a factor of 2.
      The rates of nucleotide binding, nucleotide dissociation and affinity to
      nucleotides of the two Placopecten S1s are similar and agree within a factor of
      2. In contrast, the affinity of acto.S1 for ADP is nine times weaker for the
      striated acto.S1 than for the catch acto.S1, compatible with the differences in
      motility of the Placopectenmyosins. Thus the differences in ADP affinity to
      acto.S1 and in the in vitro motility can be attributed to the differences in
      surface loop 1.

PMID- 9585568
TI  - Kinetic evidence for a readily exchangeable nucleotide at the terminal subunit of
      the barbed ends of actin filaments.
AB  - The time course of actin depolymerization was quantitatively analyzed to obtain
      insight into the reactions occurring during actin disassembly. Polymeric actin
      was diluted, and subsequently the time course of depolymerization was measured.
      In the presence of 0.5 mM ATP, 100 mM KCl, and 1 mM MgCl2, continuous
      depolymerization was observed both when the filaments were carefully diluted and
      when the filaments were fragmented to produce short filaments. The rates of the
      reactions that are known to occur during depolymerization, such as dissociation
      and association of ADP- and ATP-actin molecules and exchange of nucleotides bound
      to monomeric actin, were determined by independent experiments. When the
      determined rate parameters were used to calculate the time course of
      depolymerization, consistently in the simulations fast depolymerization of ADP
      actin was followed by slower polymerization of ATP-actin that was formed from ADP
      actin by nucleotide exchange. The lack of fast depolymerization and subsequent
      slower polymerization in the experiments suggests that our present conception
      about actin disassembly requires modification. Good agreement of calculated time
      courses with the experimentally determined continuous depolymerization was
      achieved if ADP bound to the terminal subunit of barbed filament ends was assumed
      to be readily exchangeable for ATP. Fast nucleotide exchange at terminal subunits
      may contribute to the stability of barbed filament ends and to their role as
      polymerizing ends in living cells.

PMID- 9585567
TI  - Caldesmon-actin-tropomyosin contains two types of binding sites for myosin S1.
AB  - Caldesmon inhibits the activation of myosin ATPase activity by actin-tropomyosin.
      Caldesmon also inhibits the binding of myosin to actin. There is disagreement as
      to the degree to which competitive displacement of myosin subfragment binding to
      actin is responsible for the inhibition of ATPase activity. We have examined the
      possibility that one or more molecules of S1 may bind to actin-tropomyosin
      caldesmon without having the normal actin activation of ATPase activity. The
      effect of caldesmon on the binding and ATPase activity of S1 was measured at
      several initial levels of saturation of S1 to determine if a fraction of the
      bound S1 was resistant to displacement by caldesmon. In the case of both
      unmodified S1 and rhoPDM-modified S1, most, but not all, of the S1 was displaced
      by caldesmon. The results are consistent with a single molecule of S1 binding
      with low affinity for each seven actin monomers that are fully saturated with
      caldesmon and tropomyosin. This single S1 is not necessarily bound directly to
      actin but may be attached to the NH2-terminal region of caldesmon.

PMID- 9585569
TI  - Salt effects on hydrophobic interaction and charge screening in the folding of a
      negatively charged peptide to a coiled coil (leucine zipper).
AB  - The stability of a coiled coil or leucine zipper is controlled by hydrophobic
      interactions and electrostatic forces between the constituent helices. We have
      designed a 30-residue peptide with the repeating seven-residue pattern of a
      coiled coil, (abcdefg)n, and with Glu in positions e and g of each heptad. The
      glutamate side chains prevented folding at pH values above 6 because of
      electrostatic repulsion across the helix dimer interface as well as within the
      individual helices. Protonation of the carboxylates changed the conformation from
      a random coil monomer to a coiled coil dimer. Folding at alkaline pH where the
      peptide had a net charge of -7e was promoted by the addition of salts. The nature
      of the charge screening cation was less important than that of the anion. The
      high salt concentrations (>1 M) necessary to induce folding indicated that the
      salt-induced folding resulted from alterations in the protein-water interaction.
      Folding was promoted by the kosmotropic anions sulfate and fluoride and to a
      lesser extent by the weak kosmotrope formate, whereas chloride and the strong
      chaotrope perchlorate were ineffective. Kosmotropes are excluded from the protein
      surface, which is preferentially hydrated, and this promotes folding by
      strengthening hydrophobic interactions at the coiled coil interface. Although
      charge neutralization also contributed to folding, it was effective only when the
      screening cation was partnered by a good kosmotropic anion. Folding conformed to
      a two-state transition from random coil monomer to coiled coil dimer and was
      enthalpy driven and characterized by a change in the heat capacity of unfolding
      of 3.9 +/- 1.2 kJ mol-1 K-1. The rate of folding was analyzed by fluorescence
      stopped-flow measurements. Folding occurred in a biphasic reaction in which the
      rapid formation of an initial dimer (kf = 2 x 10(7) M-1 s-1) was followed by an
      equally rapid concentration-independent rearrangement to the folded dimer (k >
      100 s-1).

PMID- 9585570
TI  - The role of Gly-4 of human cystatin A (stefin A) in the binding of target
      proteinases. Characterization by kinetic and equilibrium methods of the
      interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin
      L.
AB  - The importance of the evolutionarily conserved Gly-4 residue for the affinity and
      kinetics of interaction of cystatin A with several cysteine proteinases was
      assessed by site-directed mutagenesis. Even the smallest replacement, by Ala,
      resulted in approximately 1000-, approximately 10- and approximately 6000-fold
      decreased affinities for papain, cathepsin L, and cathepsin B, respectively.
      Substitution by Ser gave further 3-8-fold reductions in affinity, whereas the
      largest decreases, >10(5)-fold, were observed for mutations to Arg and Glu. The
      kinetics of inhibition of papain by the mutants with small side chains, Ala and
      Ser, were compatible with a one-step bimolecular reaction similar to that with
      wild-type cystatin A. The decreased affinities of these mutants for papain and
      cathepsin L were due exclusively to increased dissociation rate constants, but
      the reduced affinities for cathepsin B were due also to decreased association
      rate constants. The latter finding indicates that the intact N-terminal region
      serves as a guide directing cystatin A to the active site of cathepsin B, as has
      been proposed for cystatin C. The kinetics of binding of the mutants with charged
      side chains, Arg and Glu, to papain were consistent with a two-step binding
      mechanism, in which the mutant side chains are accommodated in the complex by a
      conformational change. The NMR solution structure of the Ala and Trp mutants
      showed only minor changes compared with wild-type cystatin A, indicating that the
      large reductions in affinity for proteinases are not due to altered structures of
      the mutants. Instead, a side chain larger than a hydrogen atom at position 4
      affects the interaction with the proteinase most likely by interfering with the
      binding of the N-terminal region.

PMID- 9585571
TI  - Kinetic folding pathway of a three-disulfide mutant of bovine pancreatic
      ribonuclease A missing the [40-95] disulfide bond.
AB  - The oxidative refolding pathway of a three-disulfide mutant of bovine pancreatic
      ribonuclease A (RNase A) from the fully reduced unfolded form to the native state
      has been studied by using oxidized and reduced dithiothreitol as the redox
      reagents at pH 8.0 and 25 degrees C. This mutant was prepared by replacing Cys40
      and Cys95 in RNase A with alanines while maintaining the other three native
      disulfide bonds to mimic one of the two major three-disulfide intermediates (des
      [40-95]) observed in the regeneration of wild-type RNase A. The kinetics of
      refolding of this mutant were measured by quenching the regeneration reaction at
      various times with a rapid blocking reagent, 2-aminoethyl methanethiosulfonate
      (AEMTS), fractionating the disulfide intermediates by using cation-exchange HPLC,
      and analyzing the time course of each group of disulfide species. It was found
      that the disulfide intermediates formed during regeneration reach a steady-state
      distribution after a short period of preequilibration similar to that in the
      regeneration of wild-type RNase A. The experimental data acquired under different
      redox conditions were fit to a kinetic model with a steady-state treatment. The
      fitted results indicate that this mutant refolds through a rate-determining step
      which involves the oxidation of certain two-disulfide species to form a putative
      three-disulfide species which proceeds rapidly to the native protein. A rough
      estimation suggests that this pathway could constitute no more than 5% of the
      major pathway leading to the formation of des-[40-95] (the major three-disulfide
      intermediate formed) in the regeneration of wild-type RNase A. Several kinetic
      constants pertaining to the oxidation and reduction of various disulfide
      intermediates were compared with those obtained in the regeneration studies of
      wild-type RNase A to gain further understanding about the folding pathways of
      RNase A. Comparisons are also given for the oxidative refolding studies of
      several other three disulfide bond proteins, suggesting that the formation of a
      large number of disulfide-bonded intermediates during oxidative refolding is
      probably a common feature for most proteins.

PMID- 9585572
TI  - Characterization of the copper chaperone Cox17 of Saccharomyces cerevisiae.
AB  - Assembly of functional cytochrome oxidase in yeast requires Cox17, which has been
      postulated to deliver copper ions to the mitochondrion for insertion into the
      enzyme. This role for Cox17 is supported by the observation that it binds copper
      as a binuclear cuprous-thiolate cluster. X-ray absorption spectroscopy, together
      with UV-visible absorption and emission spectroscopy, indicates the presence of
      bound cuprous ions, trigonally coordinated by thiolate ligands. Analysis of the
      EXAFS shows three Cu-S bonds at 2.26 A, plus a short Cu-Cu distance of 2.7 A,
      indicating a binuclear cluster in Cox17. The cuprous-thiolate cluster in Cox17 is
      substantially more labile than structurally related clusters in metallothioneins.

PMID- 9585573
TI  - 13C NMR studies of vitamin C transport and its redox cycling in human
      erythrocytes.
AB  - 13C NMR spectra of labeled [1-13C]- and [2-13C]ascorbic acid were seen to contain
      resonances arising from the intra- and extracellular populations in suspensions
      of human erythrocytes; i.e., they displayed the "split-peak" phenomenon. This new
      observation enabled the ready determination of the location, whether inside or
      outside cells, of the redox reactions in which the vitamin C was involved and to
      monitor the transport of the compounds into and out of the cells. Thus, the
      membrane permeability of ascorbic acid and the apparent Vmax and KM for the
      reduction of dehydroascorbic acid were determined in a noninvasive manner. In
      contrast to other work, evidence was found of a transporter of dehydroascorbic
      acid which is different from the glucose transporter. This transport system also
      appeared to be involved in the simultaneous reduction of dehydroascorbic acid on
      its passage into the cells. A second reduction process appeared to occur
      extracellularly, by the passage of reducing equivalents through the plasma
      membrane, as occurs with the reduction of ferricyanide. Evidence is presented
      that the processes of vitamin C recycling rely on different cellular sources of
      reducing equivalents. Whereas the transport and reduction via the membrane
      appeared to be dependent on glycolysis (NADH), the reduction of intracellular
      dehydroascorbic acid, formed in the process of transmembrane electron transfer or
      by transport from the outside of the cell, is currently thought to depend on
      NADPH.

PMID- 9585574
TI  - Modulation of phospholipase A2 activity by aminoglycosides and daptomycin: a
      Fourier transform infrared spectroscopic study.
AB  - The antibiotics known as aminoglycosides are commonly used to treat severe
      infections caused by Gram-negative bacteria. Unfortunately, they often lead to
      acute renal failure after their accumulation in the lysosomes of renal cells,
      where an inhibition of the phospholipid catabolism is observed. The lipopeptidic
      antibiotic daptomycin has been shown to reduce the nephrotoxicity of
      aminoglycosides, but the exact mechanism of this protection is still unknown. In
      the present study, Fourier transform infrared spectroscopy (FTIR) has been used
      to monitor the hydrolysis of phosphatidylcholine by phospholipase A2 (PLA2) from
      Naja mocambique mocambique venom in the presence of various aminoglycosides
      and/or daptomycin. Gentamicin and amikacin inhibited the reaction in its early
      stage. Kanamycin A, tobramycin, and especially kanamycin B enhanced the initial
      enzyme activity by reducing the lag time. After the initiation period, the
      reaction proceeded at a much slower rate in the presence of gentamicin. On the
      other hand, daptomycin led to dramatic alterations of the hydrolysis profile: the
      initial latency period was eliminated, and the maximal extent of hydrolysis was
      reduced. When both daptomycin and any of the aminoglycosides were present, the
      latency period also disappeared, and the phospholipase activity was higher than
      with the lipopeptide alone. The most drastic change occurred with gentamicin,
      which was the most inhibitory aminoglycoside when used alone but worked
      synergistically with daptomycin to yield the most dramatic activation of PLA2.

PMID- 9585575
TI  - Reductive and oxidative half-reactions of morphinone reductase from Pseudomonas
      putida M10: a kinetic and thermodynamic analysis.
AB  - The reaction of morphinone reductase (MR) with the physiological reductant NADH
      and the oxidizing substrate codeinone has been studied by multiple and single
      wavelength stopped-flow spectroscopy. Reduction of the enzyme with NADH proceeds
      in two kinetically resolvable steps. In the first step, the oxidized enzyme forms
      a charge-transfer intermediate with NADH. The charge-transfer complex is
      characterized by an increase in absorbance at long wavelength (540 to 650 nm),
      and its rate of formation is dependent on substrate concentration and is
      controlled by a second-order rate constant of 4. 8 x 10(5) M-1 s-1 at pH 7.0 and
      5 degrees C. In the second step, the enzyme-bound flavin is reduced to the
      dihydroflavin form. The rate of flavin reduction (23.4 s-1 at pH 7.0 and 5
      degrees C) is independent of substrate concentration and is observed as a
      monophasic decrease in absorbance at 462 nm. The oxidative half-reaction proceeds
      in three kinetically resolvable steps. The first is due to the formation of a
      reduced enzyme-codeinone charge-transfer complex and is observed at long
      wavelength (about 650 nm). The rate of charge-transfer complex formation is
      dependent on codeinone concentration and is controlled by a second-order rate
      constant of 11.5 x 10(3) M-1 s-1 at pH 7.0 and 5 degrees C. The second step
      represents flavin reoxidation and is observed at 462 (absorption increase) and
      650 nm (absorption decrease) and progresses with a rate (about 45 s-1) which is
      independent of codeinone concentration. The third step is observed as a further
      small increase in absorbance at 462 nm and proceeds with a rate of about 2.5 s-1.
      This step most likely represents hydrocodone release from the oxidized enzyme.
      Analysis of the temperature dependence of the reductive half-reaction has enabled
      calculation of the entropic and enthalpic contributions for charge-transfer
      formation, charge-transfer decay (yielding free enzyme and substrate), and
      electron transfer to the enzyme-bound FMN, and the construction of a partial
      energy profile for the reaction catalyzed by MR. The reaction scheme and redox
      properties of MR are compared with those described previously for the closely
      related flavoprotein, old yellow enzyme. Although common features are identified,
      there are notable differences in the kinetic and redox properties of the two
      enzymes.

PMID- 9585576
TI  - The conformation of NADH bound to inosine 5'-monophosphate dehydrogenase
      determined by transferred nuclear Overhauser effect spectroscopy.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the oxidation of inosine
      5-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP). The reaction proceeds
      with concomitant conversion of NAD+ to NADH and is the rate-limiting step in the
      de novo biosynthesis of guanosine nucleotides. IMPDH is a target for numerous
      chemotherapeutic agents. The conformations of enzyme-bound substrates, enzyme
      bound products and enzyme-bound ligands in general, are of interest for the
      understanding of the catalytic mechanism of the enzyme and the design of new
      inhibitors. Although several of the chemotherapeutic inhibitors of IMPDH are NAD+
      or NADH analogues, no structural data for IMPDH-bound NAD+ (or NADH) are
      available. In the present work, we have used transferred nuclear Overhauser
      effect spectroscopy (TRNOESY) to determine the conformation of NADH bound to the
      active site of human type II IMPDH (IMPDH-h2). The inter-proton distances
      determined from TRNOESY data indicate that NADH binds to the enzyme active site
      in an overall extended conformation. The adenosine moiety and the nicotinamide
      riboside moiety are both in the anti conformation about the glycosidic bond, and
      both ribose rings are in approximately C4'-exo conformations. The nicotinamide
      amide group was found to be in a cis conformation. The anti conformation of the
      nicotinamide riboside moiety is in accord with the preferred conformations of
      several potent and selective dinucleotide inhibitors and is consistent with that
      implied by the stereospecificity of hydride transfer in the enzymatic reaction.
      The implications of this conformation for the catalytic mechanism of IMPDH-h2 are
      discussed.

PMID- 9585577
TI  - Ca2+ coordination to backbone carbonyl oxygen atoms in calmodulin and other EF
      hand proteins: 15N chemical shifts as probes for monitoring individual-site Ca2+
      coordination.
AB  - Examination of the NMR 15N chemical shifts of a number of EF-hand proteins shows
      that the shift value for the amido nitrogen of the residue in position 8 of a
      canonical EF-hand loop (or position 10 of a pseudo EF-hand loop) provides a good
      indication of metal occupation of that site. The NH of the residue in position 8
      is covalently bonded to the carbonyl of residue 7, the only backbone carbonyl
      that coordinates to the metal ion in a canonical EF-hand loop. Upon metal
      coordination to this carbonyl, there is an appreciable deshielding of the 15N
      nucleus at position 8 (+4 to +8 ppm) due to the polarization of the O(7)=C(7)
      N(8) amido group and the corresponding reduction in the electron density of the
      nitrogen atom. This deshielding effect is effectively independent of the binding
      of metal to the other site of an EF-hand pair, allowing the 15N shifts to be used
      as probes for site-specific occupancy of metal binding sites. In addition, a Ca2+
      induced change in side-chain Halpha-Calpha-Cbeta-Hbeta torsion angle for
      isoleucine or valine residues in position 8 can also contribute to the
      deshielding of the amide 15N nucleus. This conformational effect occurs only in
      sites I or III and takes place upon binding a Ca2+ ion to the other site of an EF
      hand pair (site II or IV) regardless of whether the first site is occupied. The
      magnitude of this effect is in the range +5 to +7 ppm. A Ca2+ titration of 15N
      labeled apo-calmodulin was performed using 2D 1H-15N HSQC NMR spectra. The
      changes in the 15N chemical shifts and intensities for the peaks corresponding to
      the NH groups of residues in position 8 of the EF-hand loops allowed the amount
      of metal bound at sites II, III and IV to be monitored directly at partial
      degrees of saturation. The peak corresponding to site I could only be monitored
      at the beginning and end of the titration because of line broadening effects in
      the intermediate region of the titration. Sites III and IV both titrate
      preferentially and the results demonstrate clearly that sites in either domain
      fill effectively in parallel, consistent with a significant positive intradomain
      cooperativity of calcium binding.

PMID- 9585578
TI  - Spectroscopic evidence for interaction between transmembrane helices 3 and 5 in
      rhodopsin.
AB  - Recent molecular models of rhodopsin (Rho) propose a specific interaction between
      transmembrane (TM) helices 3 and 5, which appears to be mediated by amino acid
      residues Glu122 and His211 on TM helices 3 and 5, respectively. To test this
      proposed interaction, four single-site histidine replacement mutants (H100N,
      H152N, H211N, and H211F), two single-site glutamic acid replacement mutants
      (E122Q and E122A), and three double-site replacement mutants (E122Q/H211F,
      E122Q/H211N, and E122A/H211F) of Rho were prepared. The expressed mutant pigments
      reconstituted into membranes were studied by FTIR difference spectroscopy
      addressing especially the transition to metarhodopsin I (MI). It is shown that
      the lipid environment influences bands typical of the MI state. Spectra of
      mutants with substituted Glu122 allowed assignments of the C=O stretch of
      protonated Glu122 in the dark state and in MI of Rho. Mutation of His211, but not
      of other histidine residues, affects these vibrational modes assigned to Glu122.
      In addition, replacements of His211 affect protein modes that are proposed to
      arise from a third, hydroxyl-bearing group, which also interacts with Glu122.
      These modes are influenced as well when Glu122 is replaced by Ala in mutant E122A
      but not when it is replaced by Gln in mutant E122Q. These results provide direct
      experimental evidence for an interaction between TM helices 3 and 5 in Rho, which
      is mediated by Glu122 and His211.

PMID- 9585579
TI  - Lipid-binding characteristics of the polybasic carboxy-terminal sequence of K
      ras4B.
AB  - We have examined the association with lipid vesicles of fluorescent lipidated
      peptides based on the farnesylated, polybasic carboxy-terminal region of mature K
      ras4B, which functions physiologically as an autonomous plasma membrane-targeting
      motif. While the peptides bind to neutral lipid
      (phosphatidylcholine/phosphatidylethanolamine) vesicles with relatively low
      affinity, the vesicle-binding affinity increases exponentially as increasing
      amounts of anionic lipids are incorporated into the vesicle bilayers. Competitive
      vesicle-binding experiments reveal that the K-ras4B carboxy-terminal sequence
      accordingly discriminates strongly between lipid surfaces of differing surface
      charge, such that two lipid bilayers differing in anionic lipid content by 10 mol
      % will show a 45-fold preferential accumulation of the lipidated peptide in the
      more negatively charged surface. At the same time, the carboxyl-terminal region
      of K-ras4B exhibits no preferential binding to particular anionic lipids,
      including the polyanionic species phosphatidylinositol-4'-phosphate and
      phosphatidylinositol-4',5'-bisphosphate, beyond that predicted on the basis of
      surface-charge effects. The K-ras4B carboxyl-terminal sequence dissociates
      rapidly (with half-times of seconds or less) from lipid bilayers containing up to
      40 mol % anionic lipid. These results suggest that the targeting of the mature K
      ras4B carboxy-terminus to the plasma membrane, if it is based on interactions
      with plasma membrane lipids, is not mediated by a kinetic-trapping mechanism or
      by specific binding to particular anionic lipids but may rest on the sensitive
      surface potential-sensing function of this region of the protein.

PMID- 9585581
TI  - Dimerization of a His117Gly azurin mutant by external addition of 1, omega
      Di(imidazol-1-yl)alkanes 

PMID- 9585580
TI  - Intramolecular proton transfer from multiple sites in catalysis by murine
      carbonic anhydrase V.
AB  - The hydration of CO2 catalyzed by carbonic anhydrase requires proton transfer
      from the zinc-bound water at the active site to solution for each cycle of
      catalysis. In the most efficient of the mammalian carbonic anhydrases, isozyme
      II, this transfer is facilitated by a proton shuttle residue, His 64. Murine
      carbonic anhydrase V (mCA V) has a sterically constrained tyrosine at the
      analogous position; it is not an effective proton shuttle, yet catalysis by this
      isozyme still achieves a maximal turnover in CO2 hydration of 3 x 10(5) s-1 at pH
      > 9. We have investigated the source of proton transfer in a truncated form of
      mCA V and identified several basic residues, including Lys 91 and Tyr 131,
      located near the mouth of the active-site cavity that contribute to proton
      transfer. Intramolecular proton-transfer rates between these shuttle groups and
      the zinc-bound water were estimated as the rate-determining step in kcat for
      hydration of CO2 measured by stopped-flow spectrophotometry and in the exchange
      of 18O between CO2 and water measured by mass spectrometry. Comparison of kcat in
      catalysis by Lys 91 and Tyr 131 and the corresponding double mutant showed a
      strong antagonistic interaction between these sites, suggesting a cooperative
      behavior in facilitating the proton-transfer step of catalysis. Replacing four
      potential proton shuttle residues produced a multiple mutant that had 10% of the
      catalytic turnover kcat of the wild type, suggesting that the main proton
      shuttles have been accounted for in mCA V. These replacements caused relatively
      small changes in kcat/Km for hydration, which measures the interconversion of CO2
      and HCO3- in a stage of catalysis that is separate and distinct from the proton
      transfers; these measurements serve as a control indicating that the replacements
      of proton shuttles have not caused structural changes that affect reactivity at
      the zinc.

PMID- 9585582
TI  - Identification of cryptic rearrangements in patients with 18q- deletion syndrome.
AB  - The majority of patients with 18q- syndrome appear cytogenetically to have a
      terminal deletion of the long arm of chromosome 18. These 18q- patients are
      diagnosed by use of standard cytogenetic banding techniques, which have
      resolution insufficient for precise genotyping. In our effort to obtain a
      thorough genotype, we have analyzed the DNA from 35 patients who originally were
      diagnosed as having de novo terminal deletions of chromosome 18. Molecular
      analysis was performed with polymorphic markers throughout the 18q- region.
      Cytogenetic FISH was performed with two human 18q telomeric probes, a chromosome
      18-specific alpha-satellite probe, and whole chromosome 18-specific paint. Of 35
      patients previously reported to have terminal deletions of 18q, we found that 5
      (14%) have more-complex cryptic rearrangements and that 3 (9%) retain the most
      distal portion of 18q, consistent with an interstitial rather than a terminal
      deletion. These findings indicate that a standard karyotype can lead to
      insufficient characterization in 18q- syndrome. This has important ramifications
      for phenotype mapping of this syndrome, as well as for proper prognosis.

PMID- 9585583
TI  - Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR
      mutations.
AB  - Thirty-two unrelated patients with features of Saethre-Chotzen syndrome, a common
      autosomal dominant condition of craniosynostosis and limb anomalies, were
      screened for mutations in TWIST, FGFR2, and FGFR3. Nine novel and three recurrent
      TWIST mutations were found in 12 families. Seven families were found to have the
      FGFR3 P250R mutation, and one individual was found to have an FGFR2 VV269-270
      deletion. To date, our detection rate for TWIST or FGFR mutations is 68% in our
      Saethre-Chotzen syndrome patients, including our five patients elsewhere reported
      with TWIST mutations. More than 35 different TWIST mutations are now known in the
      literature. The most common phenotypic features, present in more than a third of
      our patients with TWIST mutations, are coronal synostosis, brachycephaly, low
      frontal hairline, facial asymmetry, ptosis, hypertelorism, broad great toes, and
      clinodactyly. Significant intra- and interfamilial phenotypic variability is
      present for either TWIST mutations or FGFR mutations. The overlap in clinical
      features and the presence, in the same genes, of mutations for more than one
      craniosynostotic condition-such as Saethre-Chotzen, Crouzon, and Pfeiffer
      syndromes-support the hypothesis that TWIST and FGFRs are components of the same
      molecular pathway involved in the modulation of craniofacial and limb development
      in humans.

PMID- 9585584
TI  - Difficulties in the estimation of ethnic affiliation.

PMID- 9585585
TI  - Paternal isodisomy of chromosome 7 associated with complete situs inversus and
      immotile cilia.

PMID- 9585586
TI  - Familial skewed X inactivation and X-linked mutations: unbalanced X inactivation
      is a powerful means to ascertain X-linked genes that affect cell proliferation.

PMID- 9585587
TI  - Haplotype mapping of a major quantitative-trait locus for fetal hemoglobin
      production, on chromosome 6q23.
AB  - Fetal hemoglobin (Hb F) and fetal cell (FC) levels in adults show considerable
      variation and are influenced by several genetic variants; the major determinants
      appear to be unlinked to the beta-globin gene cluster. Recently, a trans-acting
      locus controlling Hb F and FC production has been mapped to chromosome 6q23 in an
      Asian Indian kindred that includes individuals with heterocellular hereditary
      persistence of Hb F (HPFH) associated with beta thalassemia. We have extended the
      kindred by 57 members, bringing the total studied to 210, and have saturated the
      region with 26 additional markers. Linkage analysis showed tight linkage of the
      quantitative-trait locus (QTL) to the anonymous markers D6S976 (LOD score 11.3;
      recombination fraction .00) and D6S270 (LOD score 7.4; recombination fraction
      .00). Key recombination events now place this QTL within a 1-2-cM interval
      spanning approximately 1.5 Mb between D6S270 and D6S1626. Furthermore, haplotype
      analysis has led to a reevaluation of the genealogy and to the identification of
      additional relationships in the kindred.

PMID- 9585588
TI  - Parental origin-dependent, male offspring-specific transmission-ratio distortion
      at loci on the human X chromosome.
AB  - We have analyzed the transmission of maternal alleles at loci spanning the length
      of the X chromosome in 47 normal, genetic disease-free families. We found a
      significant deviation from the expected Mendelian 1:1 ratio of
      grandpaternal:grandmaternal alleles at loci in Xp11.4-p21.1. The distortion in
      inheritance ratio was found only among male offspring and was manifested as a
      strong bias in favor of the inheritance of the alleles of the maternal
      grandfather. We found no evidence for significant heterogeneity among the
      families, which implies that the major determinant involved in the generation of
      the non-Mendelian ratio is epigenetic. Our analysis of recombinant chromosomes
      inherited by male offspring indicates that an 11.6-cM interval on the short arm
      of the X chromosome, bounded by DXS538 and DXS7, contains an imprinted gene that
      affects the survival of male embryos.

PMID- 9585589
TI  - A global haplotype analysis of the myotonic dystrophy locus: implications for the
      evolution of modern humans and for the origin of myotonic dystrophy mutations.
AB  - Haplotypes consisting of the (CTG)n repeat, as well as several flanking markers
      at the myotonic dystrophy (DM) locus, were analyzed in normal individuals from 25
      human populations (5 African, 2 Middle Eastern, 3 European, 6 East Asian, 3
      Pacific/Australo-Melanesian, and 6 Amerindian) and in five nonhuman primate
      species. Non-African populations have a subset of the haplotype diversity present
      in Africa, as well as a shared pattern of allelic association. (CTG)18-35 alleles
      (large normal) were observed only in northeastern African and non-African
      populations and exhibit strong linkage disequilibrium with three markers flanking
      the (CTG)n repeat. The pattern of haplotype diversity and linkage disequilibrium
      observed supports a recent African-origin model of modern human evolution and
      suggests that the original mutation event that gave rise to DM-causing alleles
      arose in a population ancestral to non-Africans prior to migration of modern
      humans out of Africa.

PMID- 9585590
TI  - Evidence for autosomal dominant inheritance of prostate cancer.
AB  - A family-history cancer survey was conducted on 5,486 men who underwent a radical
      prostatectomy, for clinically localized prostate cancer, in the Department of
      Urology at the Mayo Clinic during 1966-95; 4,288 men responded to the survey.
      Complex segregation analysis was performed to assess the genetic basis of age at
      diagnosis and the familial clustering of prostate cancer. For the total group, no
      single-gene model of inheritance clearly explained familial clustering of
      disease, which could be partly explained by lack of Hardy-Weinberg equilibrium,
      with an excess of homozygotes. After accounting for deviations from Hardy
      Weinberg equilibrium, the best-fitting model that explained the familial
      aggregation and age at diagnosis was a rare autosomal dominant susceptibility
      gene, and this model fitted best when probands were diagnosed at <60 years of
      age. The model predicts that the frequency of the susceptibility gene in the
      population is .006 and that the risk of prostate cancer by age 85 years is 89%
      among carriers of the gene and 3% among noncarriers. A strength of our study is
      its large size, such that genetic models could be fitted within strata defined by
      the age of the proband. Although the autosomal dominant model was consistently
      the best model, the parameter estimates differed somewhat (P=.03) across the
      different age groups, suggesting genetic heterogeneity. Additional evidence that
      the hereditary basis of prostate cancer is likely to be genetically complex was
      provided by the following: (1) there was a significantly elevated age-adjusted
      risk of prostate cancer among brothers of probands, compared with their fathers
      (relative risk 1.5 [95% confidence interval 1.4-1.7]); (2) the autosomal dominant
      model predicted an excess of homozygotes, over that predicted by Hardy-Weinberg
      equilibrium; and (3) the model-predicted risk of prostate cancer among relatives
      was inadequate when probands were diagnosed at age >=70 years.

PMID- 9585592
TI  - Discriminating between true and false-positive peaks in a genomewide linkage
      scan, by use of the peak length.

PMID- 9585591
TI  - Genetic analysis of meiotic recombination in humans by use of sperm typing:
      reduced recombination within a heterozygous paracentric inversion of chromosome
      9q32-q34.3.
AB  - To investigate patterns of genetic recombination within a heterozygous
      paracentric inversion of chromosome 9 (46XY inv[9] [q32q34.3]), we performed
      sperm typing using a series of polymorphic microsatellite markers spanning the
      inversion region. For comparison, two donors with cytogenetically normal
      chromosomes 9, one of whom was heterozygous for a pericentric chromosome 2
      inversion (46XY inv[2] [p11q13]), were also tested. Linkage analysis was
      performed by use of the multilocus linkage-analysis program SPERM, and also CRI
      MAP, which was adapted for sperm-typing data. Analysis of the controls generated
      a marker order in agreement with previously published data and revealed no
      significant interchromosomal effects of the inv(2) on recombination on chromosome
      9. FISH employing cosmids containing appropriate chromosome 9 markers was used to
      localize the inversion breakpoint of inv(9). Analysis of inv(9) sperm was
      performed by use of a set of microsatellite markers that mapped centromeric to,
      telomeric to, and within the inversion breakpoints. Three distinct patterns of
      recombination across the region were observed. Proximal to the centromeric
      breakpoint, recombination was similar to normal levels. Distal to the telomeric
      breakpoint, there was an increase in recombination found in the inversion
      patient. Finally, within the inversion, recombination was dramatically reduced,
      but several apparent double recombinants were found. A putative model explaining
      these data is proposed.

PMID- 9585593
TI  - A model for antagonistic pleiotropic gene action for mortality and advanced age.
AB  - Association or linkage studies involving control and long-lived populations
      provide information on genes that influence longevity. However, the relationship
      between allele-specific differences in survival and the genetic structure of
      aging cohorts remains unclear. We model a heterogeneous cohort comprising several
      genotypes differing in age-specific mortality. In its most general form, without
      any specific assumption regarding the shape of mortality curves, the model
      permits derivation of a fundamental property underlying abrupt age-related
      changes in the composition of a cohort. The model is applied to sex-specific
      survival curves taken from period life tables, and Gompertz-Makeham mortality
      coefficients are calculated for the French population. Then, adjustments are
      performed under Gompertz-Makeham mortality functions for three genotypes
      composing a heterogeneous cohort, under the constraint of fitting the resultant
      mortality to the real French population mortality obtained from life tables.
      Multimodal curves and divergence after the 8th decade appear as recurrent
      features of the frequency trajectories. Finally, a fit to data previously
      obtained at the angiotensin-converting-enzyme locus is realized, explaining what
      had seemed to be paradoxical results-namely, that the frequency of a genotype
      known as a cardiovascular risk factor was increased in centenarians. Our results
      help explain the well-documented departure from Gompertz-Makeham mortality
      kinetics at older ages. The implications of our model are discussed in the
      context of known genetic effects on human longevity and age-related pathologies.
      Since antagonistic pleiotropy between early and late survival emerges as a
      general rule, extrapolating the effects measured for a gene in a particular age
      class to other ages could be misleading.

PMID- 9585594
TI  - A major locus for autosomal recessive retinitis pigmentosa on 6q, determined by
      homozygosity mapping of chromosomal regions that contain gamma-aminobutyric acid
      receptor clusters.
AB  - Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy, with
      extensive allelic and nonallelic genetic heterogeneity. Autosomal recessive RP
      (arRP) is the most common form of RP worldwide, with at least nine loci known and
      accountable for approximately 10%-15% of all cases. Gamma-aminobutyric acid
      (GABA) is the major inhibitory transmitter in the CNS. Different GABA receptors
      are expressed in all retinal layers, and inhibition mediated by GABA receptors in
      the human retina could be related to RP. We have selected chromosomal regions
      containing genes that encode the different subunits of the GABA receptors, for
      homozygosity mapping in inbred families affected by arRP. We identify a new locus
      for arRP, on chromosome 6, between markers D6S257 and D6S1644. Our data suggest
      that 10%-20% of Spanish families affected by typical arRP could have linkage to
      this new locus. This region contains subunits GABRR1 and GABRR2 of the GABA-C
      receptor, which is the effector of lateral inhibition at the retina.

PMID- 9585595
TI  - Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence
      of haplotypes.
AB  - The CCR5-Delta32 deletion obliterates the CCR5 chemokine and the human
      immunodeficiency virus (HIV)-1 coreceptor on lymphoid cells, leading to strong
      resistance against HIV-1 infection and AIDS. A genotype survey of 4,166
      individuals revealed a cline of CCR5-Delta32 allele frequencies of 0%-14% across
      Eurasia, whereas the variant is absent among native African, American Indian, and
      East Asian ethnic groups. Haplotype analysis of 192 Caucasian chromosomes
      revealed strong linkage disequilibrium between CCR5 and two microsatellite loci.
      By use of coalescence theory to interpret modern haplotype genealogy, we estimate
      the origin of the CCR5-Delta32-containing ancestral haplotype to be approximately
      700 years ago, with an estimated range of 275-1,875 years. The geographic cline
      of CCR5-Delta32 frequencies and its recent emergence are consistent with a
      historic strong selective event (e.g. , an epidemic of a pathogen that, like HIV
      1, utilizes CCR5), driving its frequency upward in ancestral Caucasian
      populations.

PMID- 9585596
TI  - Genetic mapping of ossification of the posterior longitudinal ligament of the
      spine.
AB  - Ossification of the posterior longitudinal ligament of the spine (OPLL) is
      recognized as a common disorder among Japanese and throughout Asia. Estimates of
      its prevalence are in the range of 1. 9%-4.3%. Although its etiology is thought
      to involve a multiplicity of factors, epidemiological and family studies strongly
      implicate genetic susceptibility in the pathogenesis of OPLL. In this study we
      report an identification of a predisposing locus for OPLL, on chromosome 6p,
      close to the HLA complex. The evidence for this localization is provided by a
      genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this
      sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence
      for strongly significant linkage (P = .000006) to the OPLL locus. A candidate
      gene in the region, that for collagen 11A2, was analyzed for the presence of
      molecular variants in affected probands. Of 19 distinct variants identified, 4
      showed strong statistical associations with OPLL (highest P = .0004). These
      observations of linkage and association, taken together, show that a genetic
      locus for OPLL lies close to the HLA region, on chromosome 6p.

PMID- 9585597
TI  - Mutation rate in human microsatellites: influence of the structure and length of
      the tandem repeat.
AB  - In 10,844 parent/child allelic transfers at nine short-tandem-repeat (STR) loci,
      23 isolated STR mismatches were observed. The parenthood in each of these cases
      was highly validated (probability >99.97%). The event was always repeat related,
      owing to either a single-step mutation (n=22) or a double-step mutation (n=1).
      The mutation rate was between 0 and 7 x 10(-3) per locus per gamete per
      generation. No mutations were observed in three of the nine loci. Mutation events
      in the male germ line were five to six times more frequent than in the female
      germ line. A positive exponential correlation between the geometric mean of the
      number of uninterrupted repeats and the mutation rate was observed. Our data
      demonstrate that mutation rates of different loci can differ by several orders of
      magnitude and that different alleles at one locus exhibit different mutation
      rates.

PMID- 9585598
TI  - Systematic analysis of molecular defects in the ferrochelatase gene from patients
      with erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP; MIM 177000) is an inherited disorder caused
      by partial deficiency of ferrochelatase (FECH), the last enzyme in the heme
      biosynthetic pathway. In EPP patients, the FECH deficiency causes accumulation of
      free protoporphyrin in the erythron, associated with a painful skin
      photosensitivity. In rare cases, the massive accumulation of protoporphyrin in
      hepatocytes may lead to a rapidly progressive liver failure. The mode of
      inheritance in EPP is complex and can be either autosomal dominant with low
      clinical penetrance, as it is in most cases, or autosomal recessive. To acquire
      an in-depth knowledge of the genetic basis of EPP, we conducted a systematic
      mutation analysis of the FECH gene, following a procedure that combines the exon
      by-exon denaturing-gradient-gel-electrophoresis screening of the FECH genomic DNA
      and direct sequencing. Twenty different mutations, 15 of which are newly
      described here, have been characterized in 26 of 29 EPP patients of Swiss and
      French origin. All the EPP patients, including those with liver complications,
      were heterozygous for the mutations identified in the FECH gene. The deleterious
      effect of all missense mutations has been assessed by bacterial expression of the
      respective FECH cDNAs generated by site-directed mutagenesis. Mutations leading
      to a null allele were a common feature among three EPP pedigrees with liver
      complications. Our systematic molecular study has resulted in a significant
      enlargement of the mutation repertoire in the FECH gene and has shed new light on
      the hereditary behavior of EPP.

PMID- 9585599
TI  - Missense mutations in disease genes: a Bayesian approach to evaluate causality.
AB  - The problem of interpreting missense mutations of disease-causing genes is an
      increasingly important one. Because these point mutations result in alteration of
      only a single amino acid of the protein product, it is often unclear whether this
      change alone is sufficient to cause disease. We propose a Bayesian approach that
      utilizes genetic information on affected relatives in families ascertained
      through known missense-mutation carriers. This method is useful in evaluating
      known disease genes for common disease phenotypes, such as breast cancer or
      colorectal cancer. The posterior probability that a missense mutation is disease
      causing is conditioned on the relationship of the relatives to the proband, the
      population frequency of the mutation, and the phenocopy rate of the disease. The
      approach is demonstrated in two cancer data sets: BRCA1 R841W and APC I1307K. In
      both examples, this method helps establish that these mutations are likely to be
      disease causing, with Bayes factors in favor of causality of 5.09 and 66.97,
      respectively, and posterior probabilities of .836 and .985. We also develop a
      simple approximation for rare alleles and consider the case of unknown penetrance
      and allele frequency.

PMID- 9585600
TI  - Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for
      antenatal Bartter syndrome.
AB  - Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders
      associated with hypokalemic alkalosis. This disorder typically presents as a life
      threatening condition beginning in utero, with marked fetal polyuria that leads
      to polyhydramnios and premature delivery. Another hallmark of this variant is a
      marked hypercalciuria and, as a secondary consequence, the development of
      nephrocalcinosis and osteopenia. We have analyzed 15 probands belonging to 13
      families and have performed SSCP analysis of the coding sequence and the exon
      intron boundaries of the NKCC2 gene; and we report 14 novel mutations in patients
      with antenatal Bartter syndrome, as well as the identification of three isoforms
      of human NKCC2 that arise from alternative splicing.

PMID- 9585601
TI  - Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein
      syndrome with hepatic-intestinal presentation.

PMID- 9585603
TI  - Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients
      and their families.
AB  - Alagille syndrome (AGS) is a dominantly inherited disorder characterized by liver
      disease in combination with heart, skeletal, ocular, facial, renal, and
      pancreatic abnormalities. We have recently demonstrated that Jagged1 (JAG1) is
      the AGS gene. JAG1 encodes a ligand in the Notch intercellular signaling pathway.
      AGS is the first developmental disorder to be associated with this pathway and
      the first human disorder caused by a Notch ligand. We have screened 54 AGS
      probands and family members to determine the frequency of mutations in JAG1.
      Three patients (6%) had deletions of the entire gene. Of the remaining 51
      patients, 35 (69%) had mutations within JAG1, identified by SSCP analysis. Of the
      35 identified intragenic mutations, all were unique, with the exceptions of a 5
      bp deletion in exon 16, seen in two unrelated patients, and a C insertion at base
      1618 in exon 9, also seen in two unrelated patients. The 35 intragenic mutations
      included 9 nonsense mutations (26%); 2 missense mutations (6%); 11 small
      deletions (31%), 8 small insertions (23%), and 1 complex rearrangement (3%), all
      leading to frameshifts; and 4 splice-site mutations (11%). The mutations are
      spread across the coding sequence of the gene within the evolutionarily conserved
      motifs of the JAG1 protein. There is no phenotypic difference between patients
      with deletions of the entire JAG1 gene and those with intragenic mutations, which
      suggests that one mechanism involved in AGS is haploinsufficiency. The two
      missense mutations occur at the same amino acid residue. The mechanism by which
      these missense mutations lead to the disease is not yet understood; however, they
      suggest that mechanisms other than haploinsufficiency may result in the AGS
      phenotype.

PMID- 9585602
TI  - X-Linked chronic granulomatous disease: mutations in the CYBB gene encoding the
      gp91-phox component of respiratory-burst oxidase.
AB  - Chronic granulomatous disease (CGD) is a hereditary disorder of host defense due
      to absent or decreased activity of phagocyte NADPH oxidase. The X-linked form of
      the disease derives from defects in the CYBB gene, which encodes the 91-kD
      glycoprotein component (termed "gp91-phox") of the oxidase. We have identified
      the mutations in the CYBB gene responsible for X-linked CGD in 131 consecutive
      independent kindreds. Screening by SSCP analysis identified mutations in 124 of
      the kindreds, and sequencing of all exons and intron boundary regions revealed
      the other seven mutations. We detected 103 different specific mutations; no
      single mutation appeared in more than seven independent kindreds. The types of
      mutations included large and small deletions (11%), frameshifts (24%), nonsense
      mutations (23%), missense mutations (23%), splice-region mutations (17%), and
      regulatory-region mutations (2%). The distribution of mutations within the CYBB
      gene exhibited great heterogeneity, with no apparent mutational hot spots.
      Evaluation of 87 available mothers revealed X-linked carrier status in all but
      10. The heterogeneity of mutations and the lack of any predominant genotype
      indicate that the disease represents many different mutational events, without a
      founder effect, as is expected for a disorder with a previously lethal phenotype.

PMID- 9585604
TI  - A triplet repeat on 17q accounts for most expansions detected by the repeat
      expansion-detection technique.

PMID- 9585605
TI  - Mutation analysis of UBE3A in Angelman syndrome patients.
AB  - Angelman syndrome (AS) is caused by chromosome 15q11-q13 deletions of maternal
      origin, by paternal uniparental disomy (UPD) 15, by imprinting defects, and by
      mutations in the UBE3A gene. UBE3A encodes a ubiquitin-protein ligase and shows
      brain-specific imprinting. Here we describe UBE3A coding-region mutations
      detected by SSCP analysis in 13 AS individuals or families. Two identical de novo
      5-bp duplications in exon 16 were found. Among the other 11 unique mutations, 8
      were small deletions or insertions predicted to cause frameshifts, 1 was a
      mutation to a stop codon, 1 was a missense mutation, and 1 was predicted to cause
      insertion of an isoleucine in the hect domain of the UBE3A protein, which
      functions in E2 binding and ubiquitin transfer. Eight of the cases were familial,
      and five were sporadic. In two familial cases and one sporadic case, mosaicism
      for UBE3A mutations was detected: in the mother of three AS sons, in the maternal
      grandfather of two AS first cousins, and in the mother of an AS daughter. The
      frequencies with which we detected mutations were 5 (14%) of 35 in sporadic cases
      and 8 (80%) of 10 in familial cases.

PMID- 9585606
TI  - The hemochromatosis 845 G-->A and 187 C-->G mutations: prevalence in non
      Caucasian populations.
AB  - Hemochromatosis, the inherited disorder of iron metabolism, leads, if untreated,
      to progressive iron overload and premature death. The hemochromatosis gene, HFE,
      recently has been identified, and characterization of this gene has shown that it
      contains two mutations that result in amino acid substitutions-cDNA nucleotides
      845 G-->A (C282Y) and 187 C-->G (H63D). Although hemochromatosis is common in
      Caucasians, affecting >=1/300 individuals of northern European origin, it has not
      been recognized in other populations. The present study used PCR and restriction
      enzyme digestion to analyze the frequency of the 845 G-->A and 187 C-->G
      mutations in HLA-typed samples from non-Caucasian populations, comprising
      Australian Aboriginal, Chinese, and Pacific Islanders. Results showed that the
      845 G-->A mutation was present in these populations (allele frequency 0.32%),
      and, furthermore, it was always seen in conjunction with HLA haplotypes common in
      Caucasians, suggesting that 845 G-->A may have been introduced into these
      populations by Caucasian admixture. 187 C-->G was present at an allele frequency
      of 2.68% in the two populations analyzed (Australian Aboriginal and Chinese). In
      the Australian Aboriginal samples, 187 C-->G was found to be associated with HLA
      haplotypes common in Caucasians, suggesting that it was introduced by recent
      admixture. In the Chinese samples analyzed, 187 C-->G was present in association
      with a wide variety of HLA haplotypes, showing this mutation to be widespread and
      likely to predate the more genetically restricted 845 G-->A mutation.

PMID- 9585607
TI  - Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2
      43.
AB  - There is genetic predisposition associated with >=10% of all cancer of the
      prostate (CaP). By means of a genomewide search on a selection of 47 French and
      German families, parametric and nonparametric linkage (NPL) analysis allowed
      identification of a locus, on chromosome 1q42.2-43, carrying a putative
      predisposing gene for CaP (PCaP). The primary localization was confirmed with
      several markers, by use of three different genetic models. We obtained a maximum
      two-point LOD score of 2.7 with marker D1S2785. Multipoint parametric and NPL
      analysis yielded maximum HLOD and NPL scores of 2.2 and 3.1, respectively, with
      an associated P value of . 001. Homogeneity analysis with multipoint LOD scores
      gave an estimate of the proportion of families with linkage to this locus of 50%,
      with a likelihood ratio of 157/1 in favor of heterogeneity. Furthermore, the 9/47
      families with early-onset CaP at age <60 years gave multipoint LOD and NPL scores
      of 3.31 and 3.32, respectively, with P = .001.

PMID- 9585608
TI  - Evidence of founder mutations in Finnish BRCA1 and BRCA2 families.

PMID- 9585609
TI  - Temperature-sensitive phenotypes of peroxisome-assembly processes represent the
      milder forms of human peroxisome-biogenesis disorders.

PMID- 9585610
TI  - Identification of a new locus for a peculiar form of congenital muscular
      dystrophy with early rigidity of the spine, on chromosome 1p35-36.
AB  - Classical congenital muscular dystrophies (CMDs) are autosomal recessive
      neuromuscular disorders characterized by early onset of hypotonia and weakness,
      atrophy of limbs and trunk muscles, contractures, and dystrophic changes in the
      muscle biopsy. So far, only one gene, LAMA2 (6q2), which encodes the laminin
      alpha2 chain (or merosin), has been identified in these disorders. Mutations in
      LAMA2 cause CMD with complete or partial merosin deficiency, detectable by
      immunocytochemistry on muscle biopsies, and account for approximately 50% of CMD
      cases. In a large consanguineous family (11 siblings) comprising three children
      affected by CMD without merosin deficiency, we undertook a genomewide search by
      homozygosity mapping and analyzed 380 microsatellite markers. The affected
      children were homozygous for several markers on chromosome 1p35-36. We identified
      two additional consanguineous families with affected children who also showed
      linkage to this locus. A maximum cumulative LOD score of 4.48, at a recombination
      fraction of .00, was obtained with D1S2885. A consistent feature in these three
      families was the presence of early rigidity of the spine, scoliosis, and reduced
      vital capacity, as found in rigid-spine syndrome (RSS). This study is the first
      description of a locus for a merosin-positive CMD and will help to better define
      the nosology of RSS.

PMID- 9585611
TI  - Genotype-phenotype correlations in attenuated adenomatous polyposis coli.
AB  - Germ-line mutations of the tumor suppressor APC are implicated in attenuated
      adenomatous polyposis coli (AAPC), a variant of familial adenomatous polyposis
      (FAP). AAPC is recognized by the occurrence of <100 colonic adenomas and a later
      onset of colorectal cancer (age >40 years). The aim of this study was to assess
      genotype-phenotype correlations in AAPC families. By protein-truncation test
      (PTT) assay, the entire coding region of the APC gene was screened in affected
      individuals from 11 AAPC kindreds, and their phenotypic differences were
      examined. Five novel germ-line APC mutations were identified in seven kindreds.
      Mutations were located in three different regions of the APC gene: (1) at the 5'
      end spanning exons 4 and 5, (2) within exon 9, and (3) at the 3' distal end of
      the gene. Variability in the number of colorectal adenomas was most apparent in
      individuals with mutations in region 1, and upper-gastrointestinal manifestations
      were more severe in them. In individuals with mutations in either region 2 or
      region 3, the average number of adenomas tended to be lower than those in
      individuals with mutations in region 1, although age at diagnosis was similar. In
      all AAPC kindreds, a predominance of right-sided colorectal adenomas and rectal
      polyp sparing was observed. No desmoid tumors were found in these kindreds. Our
      data suggest that, in AAPC families, the location of the APC mutation may
      partially predict specific phenotypic expression. This should help in the design
      of tailored clinical-management protocols in this subset of FAP patients.

PMID- 9585612
TI  - Amerindian pyruvate carboxylase deficiency is associated with two distinct
      missense mutations.
AB  - We characterized the pyruvate carboxylase (PC) gene by PCR amplification,
      subcloning, and sequencing. The coding region has 19 exons and 18 introns
      spanning approximately 16 kb of genomic DNA. Screening both the cDNA and the gene
      of individuals with the simple A form of PC deficiency revealed an 1828G-->A
      missense mutation in 11 Ojibwa and 2 Cree patients and a 2229G-->T transversion
      mutation in 2 brothers of Micmac origin. Carrier frequency may be as high as 1/10
      in some groupings. The two point mutations are located in a region of homology
      conserved among yeast, rat, and human PC, in the vicinity of the carboxylation
      domain of the enzyme. These data provide the first characterization of the human
      PC gene structure, the identification of common pathogenic mutations, and the
      demonstration of a founder effect in the Ojibwa and Cree patients.

PMID- 9585613
TI  - Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111
      families: results of an international study.
AB  - Several BRCA2 mutations are found to occur in geographically diverse breast and
      ovarian cancer families. To investigate both mutation origin and mutation
      specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic
      short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111
      breast or breast/ovarian cancer families selected for having one of nine
      recurrent BRCA2 mutations. Six of the individual mutations are estimated to have
      arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in
      approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to
      have arisen 29 generations ago (1-LOD support interval 22-38). This is
      substantially more recent than the estimated age of the BRCA1 185delAG mutation
      (46 generations), derived from our analogous study of BRCA1 mutations. In
      general, there was no evidence of multiple origins of identical BRCA2 mutations.
      Our study data were consistent with the previous report of a higher incidence of
      ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the
      ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not
      statistically significant. There was significant evidence that age at diagnosis
      of breast cancer varied by mutation (P<.001), although only 8% of the variance in
      age at diagnosis could be explained by the specific mutation, and there was no
      evidence of family-specific effects. When the age at diagnosis of the breast
      cancer cases was examined by OCCR, cases associated with mutations in the OCCR
      had a significantly older mean age at diagnosis than was seen in those outside
      this region (48 years vs. 42 years; P=.0005).

PMID- 9585614
TI  - Linkage of familial Hibernian fever to chromosome 12p13.
AB  - Autosomal dominant periodic fevers are characterized by intermittent febrile
      attacks of unknown etiology and by recurrent abdominal pains. The biochemical and
      molecular bases of all autosomal dominant periodic fevers are unknown, and only
      familial Hibernian fever (FHF) has been described as a distinct clinical entity.
      FHF has been reported in three families-the original Irish-Scottish family and
      two Irish families with similar clinical features. We have undertaken a
      genomewide search in these families and report significant multipoint LOD scores
      between the disease and markers on chromosome 12p13. Cumulative multipoint
      linkage analyses indicate that an FHF gene is likely to be located in an 8-cM
      interval between D12S77 and D12S356, with a maximum LOD score (Z max) of 3.79.
      The two-point Z max was 3.11, for D12S77. There was no evidence of genetic
      heterogeneity in these three families; it is proposed that these markers should
      be tested in other families, of different background, that have autosomal
      dominant periodic fever, as a prelude to identification of the FHF-susceptibility
      gene.

PMID- 9585615
TI  - Hyperphenylalaninemia with high levels of 7-biopterin is associated with
      mutations in the PCBD gene encoding the bifunctional protein pterin-4a
      carbinolamine dehydratase and transcriptional coactivator (DCoH).
AB  - Pterin-4a-carbinolamine dehydratase (PCD) is required for efficient
      tetrahydrobiopterin regeneration after phenylalanine hydroxylase activity. This
      catalytic function was proposed to be specifically defective in newborns with a
      mild form of hyperphenylalaninemia (HPA) and persistent high urinary levels of
      primapterin (7-biopterin). A second regulatory task of the same protein is DCoH,
      a coactivation of transcription by hepatocyte nuclear factor 1alpha (HNF-1alpha),
      a function that is apparently not impaired in these HPA individuals. It has been
      shown elsewhere that the human PCD/DCoH bifunctional protein is encoded by a
      single 4-exon-containing gene, PCBD, located on chromosome 10q22. We have now
      examined the PCBD gene for mutations at the genomic level in six such HPA
      patients from four different families. By the use of new intron-specific primers,
      we detected, in all six patients, single, homozygous nucleotide alterations, in
      exon 4, that were inherited from their parents. These homozygous alterations
      predicted mutant PCD/DCoH with a single amino acid exchange, in two cases
      (alleles T78I), or premature stop codons, in the other four patients (alleles
      E86X and Q97X). Recombinant expression in Escherichia coli revealed that the
      mutant proteins-T78I, E86X, and Q97X-are almost entirely in the insoluble
      fraction, in contrast to wild type, which is expressed as a soluble protein.
      These data support the proposal that HPA in combination with urinary primapterin
      may be due to autosomal recessive inheritance of mutations in the PCBD gene
      specifically affecting the dehydratase activity.

PMID- 9585617
TI  - A breast cancer patient of Scottish descent with germ-line mutations in BRCA1 and
      BRCA2.

PMID- 9585616
TI  - An alternative route for multistep tumorigenesis in a novel case of hereditary
      renal cell cancer and a t(2;3)(q35;q21) chromosome translocation.
AB  - Through allele-segregation and loss-of-heterozygosity analyses, we demonstrated
      loss of the translocation-derivative chromosome 3 in five independent renal cell
      tumors of the clear-cell type, obtained from three members of a family in which a
      constitutional t(2;3)(q35;q21) was encountered. In addition, analysis of the von
      Hippel-Lindau gene, VHL, revealed distinct insertion, deletion, and substitution
      mutations in four of the five tumors tested. On the basis of these results, we
      conclude that, in this familial case, an alternative route for renal cell
      carcinoma development is implied. In contrast to the first hit in the generally
      accepted two-hit tumor-suppressor model proposed by Knudson, the familial
      translocation in this case may act as a primary oncogenic event leading to
      (nondisjunctional) loss of the der(3) chromosome harboring the VHL tumor
      suppressor gene. The risk of developing renal cell cancer may be correlated
      directly with the extent of somatic (kidney) mosaicism resulting from this loss.

PMID- 9585618
TI  - Classification of familial adenomatous polyposis: a diagnostic nightmare.

PMID- 9585625
TI  - Radiology entering the new millennium accomplishments and challenges.

PMID- 9585619
TI  - Cytosine methylation and the unequal developmental potentials of the oocyte and
      sperm genomes.

PMID- 9585621
TI  - Genetic causes of female infertility: targeted mutagenesis in mice.

PMID- 9585626
TI  - [Endovascular treatment of epistaxis].

PMID- 9585627
TI  - [What is your diagnosis? Epidermoid cyst].

PMID- 9585628
TI  - [Benign vertebral osteoblastoma. Report of 6 cases].
AB  - We present six cases of benign spinal osteoblastoma. This localization of this
      uncommon benign bone tumor occurring in young subjects is rare. The patients were
      explored with radiotomography, computed tomography, myelography and medullo
      spinal angiography. These benign tumors may appear radiographically as pure bone
      lysis mimicking malignancy. The size of these tumors often leads to widening
      search for extension, particularly in recurrent, aggressive, multifocal forms
      which require wide resection, and sometimes total vertebrectomy. Medullo-spinal
      angiography can confirm the vascular involvement of the tumor nidus and is
      require to identify arteries supplying the spinal canal which would modify
      operative strategy.

PMID- 9585629
TI  - [MRI symptomatology of non-tumoral myelopathies].
AB  - We present a retrospective study in order to analyze the abnormalities noted on
      MRI in 27 cases of myelopathy excluding tumors, explored between 1994 and 1996.
      The different lesions were: Multiple Sclerosis (n = 11), Spondylotic myelopathy
      (n = 3), Neurosarcoidosis (n = 4), CMV Myelitis (n = 1), Radiation Myelopathy (n
      = 1), Spinal Dural Arteriovenous Fistula (n = 1), Intramedullary Cysticercosis (n
      = 1), Infarct (n = 5). The exams have been made on 1.5 Tesla Magnetom Vision
      Siemens or GE Signa machine. All patients have had axial and sagittal views with
      coronal complementary study in 4 cases. Sequences were Spin echo pT1 (TR: 560,
      TE: 12), Fast Spin echo pT2 (TR: 3 500, TE: 99 or 128), and gradient echo pT2
      (TR: 700, TE: 22, Angle: 25 degrees). Intravenous injection of Gadolinium has
      been made in 16 cases (0.1 mmol/kg). We have studied the presence or not of a
      signal abnormality in pT1 and/or in pT2, of enhancement, and its topography
      (cervical, thoracic, lumbar). We classified lesions in central and/or peripheral
      and according, to their topography in anterior, posterior or lateral type. The
      form has been classified in four types (nodular, triangular, "pen like", plage).
      Extension in transversal (superior or inferior to half medullary surface) and
      cranio-caudal directions (inferior to one vertebrae, between one and two
      vertebrae, superior to two vertebrae) has been also classified. Others intra or
      perimedullar and encephalic abnormalities have been noted. We analyzed the
      results for each pathology and underline the essential diagnosis criteria noted
      (low cranio-caudal and transversal extension with frequent triangular form of
      Multiple Sclerosis lesions, frequent suggestive abnormalities of the encephale
      (82%) in Multiple Sclerosis, intra and perimedullar enhancement with deformations
      of the surface of the spinal cord in Sarcoidosis' lesions, extended dorsolumbar
      "pen like" lesions with inconstant enhancement of infarcts, focal plage lesions
      centered on degenerative changes of the spinal canal in spondylotic myelopathy,
      bony lipomatous involution in front of intramedullary radiation plage lesion...)
      and also review the literature and confront their results to it. We insist on the
      difficulties in classifying myelopathy (radio-clinical terminology discordances,
      identical signal abnormalities frequently caused by different illness, necessity
      to compare to pathologic results). We propose a MRI study protocol that should
      interest the whole spinal cord and comport T1 weighted without and after
      gadolinium sequences, T2 weighted sequences (with always a gradient echo type). 2
      or better 3 different plans should be made. A complementary study of the brain by
      MRI is often useful. Clinical study, biology, evolution, MRI and when possible
      pathology all are necessary to better understand myelopathy's mechanisms.

PMID- 9585630
TI  - MR demonstration of spontaneous acute spinal subdural hematoma.
AB  - We report an unusual case of spontaneous acute spinal subdural hematoma. To date,
      only a few cases of magnetic resonance imaging (MRI) demonstration of such a
      pathology have been reported in the medical literature. We analyse the
      pathogenesis, clinical presentation, magnetic resonance imaging results,
      intraoperative findings and prognosis of this rare condition. We would like to
      stress that prompt and non-invasive diagnosis by MRI sagittal sections leads to
      efficient surgical treatment.

PMID- 9585631
TI  - Anterior (atypical) callosal absence due to cortical dysplasia and
      schizencephaly.
AB  - The corpus callosum develops from anterior to posterior, starting at the
      commissural plate of the lamina terminalis. We report a patient with cortical
      dysplasia and schizencephaly, which apparently interfered with the normal
      callosal development before 20 gestational weeks. The result was an atypical
      callosal dysgenesis in which the anterior parts (including anterior body, genu
      and rostrum) were absent while the remaining parts were developed. This finding
      suggests that the commissural plate may not be the only region where the corpus
      callosum starts to develop in some congenital brain malformations.

PMID- 9585632
TI  - Holoprosencephaly manifesting with fusion of the gyri cinguli.
AB  - In this paper we report a 7-month-old boy with lobar holoprosencephaly in whom
      midline interhemispheric fusion occurred between thickened gyri cinguli of both
      hemispheres at the middle frontal region. This anomaly appears to be a variation
      of a recently recognized type of holoprosencephaly associated with midline
      interhemispheric fusion and atypical callosal dysgenesis. In contrast to the
      previously reported a few cases, in our patient the corpus callosum was thinned
      but intact. In addition, the condition was associated with diffuse cortical
      dysplasia. The malformations in this patient is of interest because it
      contributes to our understanding of variations of holoprosencephaly.

PMID- 9585633
TI  - [NMR spectroscopy and brain diseases. Clinical applications].
AB  - Magnetic resonance spectroscopy (MRS) is a noninvasive means of obtaining
      metabolic information complementary to magnetic resonance imaging. Its potential
      is particularly interesting in tissue characterization and follow-up of brain
      lesions. We present here a review of clinical applications together with a short
      development of the fundamental principles. From a review of the literature, and
      our own experience, we discuss the role of MRS in clinical neuroimaging. Despite
      the small number of clinical applications validated to date, MRS is today a
      highly useful research tool.

PMID- 9585634
TI  - Qualitative inquiry: an overview for pediatric psychology.
AB  - OBJECTIVE: To provide a framework for critically evaluating qualitative research
      to professionals interested in pediatric psychology. Qualitative methods
      emphasize the phenomenological experience of participants and may be pertinent to
      studying contextual factors that contribute to child health and well-being.
      METHOD: A basic overview of the types of qualitative research, methodological
      procedures, and ethical considerations is provided. Examples are drawn from
      qualitative studies that focus on child and family health. RESULTS: The article
      concludes with guidelines for examining qualitative research and recommendations
      for use in pediatric psychology. CONCLUSION: Qualitative methods have the
      potential to address important issues in pediatric psychology.

PMID- 9585635
TI  - Diagnosing developmental problems in children: parents and professionals
      negotiate bad news.
AB  - OBJECTIVE: To examine how parents and professionals engage in a process of
      negotiation over what labels to use and what developmental meaning to ascribe to
      those labels when imparting a diagnosis of mental disability to parents of young
      children. METHOD: We performed a sociolinguistic analysis of 10 feedback sessions
      with parents whose children had been diagnosed by a clinical team as
      developmentally disabled. RESULTS: Professionals shied away from explicit use of
      labels; they preferred to describe children's deficits with rate descriptors
      (e.g., "slow"). Parties to the sessions see-sawed between optimistic and
      pessimistic statements. That is, when parents seemed despairing, professionals
      would try to hold out hope; when parents were unrealistic, professionals gave
      more blunt statements. Parents who received the most ambiguous interpretations
      seemed left with diagnostic questions still unanswered; those who received more
      forthright information appeared better able to move on to issues of prognosis.
      CONCLUSIONS: Diagnoses of developmental disabilities are jointly constructed by
      parents and professionals. We recommend larger and more controlled studies on the
      relationship between negotiation and labeling in diagnostic feedback interviews
      and the impact of these processes on parental satisfaction and adaptation.

PMID- 9585636
TI  - A qualitative study of Parent to Parent support for parents of children with
      special needs. Consortium to evaluate Parent to Parent.
AB  - OBJECTIVE: To examine qualitatively the experiences of parents participating in
      Parent to Parent programs. METHOD: Twenty-four parents of children with special
      needs, a subset of subjects in a larger quantitative study, participated in a
      semi-structured telephone interview to explore the impact and meaning of being
      matched with a trained supporting parent. RESULTS: Qualitative analysis reveals a
      successful match is contingent upon creation of a "reliable ally" in the
      supporting parent, comprised of four main components: (1) perceived sameness, (2)
      situational comparisons that enable learning and growth, (3) round-the-clock
      availability of support, and (4) mutuality of support. CONCLUSIONS: Parent to
      Parent support creates a community of similar others trained to listen and be
      supportive and provides an opportunity for matched parents to experience equality
      and mutuality in their relationship. Findings also identify the need for quality
      control in Parent to Parent programs and the importance of such programs as an
      adjunct to traditional professional services.

PMID- 9585637
TI  - Problem behaviors and personality of children and adolescents with Prader-Willi
      syndrome.
AB  - OBJECTIVE: Compare behavioral and emotional problems of children and adolescents
      with Prader-Willi Syndrome (PWS) and clients consulting mental health centers
      (MHC) and related behavioral and emotional problems to the children's personality
      in the PWS group. METHODS: Participants were 39 children with PWS and 585 matched
      MHC clients. Child Behavior Checklist (CBCL) syndromes were related to the Big
      Five personality factors measured with the California Child Q-sort (CCQ).
      RESULTS: Mean CBCL Total Problems scores were not different for the PWS and MHC
      groups, but differences were found for several of the CBCL subscales. Patterns of
      correlations among CBCL scales were similar in both groups, although coefficients
      were generally higher in the PWS group, indicating higher comorbidity or co
      absence of CBCL syndromes in children and adolescents with PWS. Personality
      profiles were specific for internalizing and Externalizing problems of children
      and adolescents with PWS.

PMID- 9585638
TI  - Social support, social conflict, and adjustment among adolescents with cancer.
AB  - OBJECTIVE: Evaluate support and conflict in close relationships of adolescents in
      active medical treatment for cancer. Family and friend perceptions of supportive
      and conflictual behaviors were examined in relation to psychological distress,
      taking into account the impact of functional impairment induced by the illness.
      METHODS: Using self-report questionnaires, 50 adolescents between the ages of 12
      and 20 years rated the frequency of supportive and conflictual interactions with
      parents, siblings and best friends. RESULTS: Results indicated that perceived
      maternal conflict was associated with psychological distress. Conflict with
      fathers, siblings, and best friends was not associated with distress. Supportive
      aspects of close relationships did not predict psychological distress. The amount
      of physical impairment accounted for the most variance in distress, contributing
      between 35% and 38% of the variance. CONCLUSION: Results suggest that mother
      adolescent conflict would be an appropriate target for psychosocial
      interventions.

PMID- 9585639
TI  - Child-rearing practices of primary caregivers of children with sickle cell
      disease: the perspective of professionals and caregivers.
AB  - OBJECTIVE: To obtain caregiver and medical professional opinions regarding the
      child-rearing practices of caregivers of children with sickle cell diseases
      (SCD). METHODS: We obtained self-reports of parenting practices from 48
      caregivers of children with SCD and 48 caregivers of matched classroom comparison
      peers using the Child-Rearing Practices Report (CRPR). CRPR ratings were also
      obtained from 12 experts in pediatric SCD regarding their predictions of how a
      parent of a child with SCD would respond. The experts predicted differences in
      protectiveness, discipline, and excessive worry. Objective interim and lifetime
      illness severity scores were obtained for the children with SCD. RESULTS:
      Caregivers showed similarity between the two groups, disagreement with the
      experts, and minimal relationship to illness severity. CONCLUSIONS: Experts who
      work with children with chronic illnesses such as SCD seem to have stereotyped
      ideas that do not correspond with parental reports of their child-rearing
      practices, suggesting the need for careful clinical evaluations.

PMID- 9585640
TI  - Brief report: assessment of body image in survivors of childhood cancer.
AB  - OBJECTIVE: To establish preliminary reliability and validity data of the Body
      Image Instrument (BII), a 28-item self-report measure developed to assess body
      image in adolescents and young adults with cancer. METHOD: As part of a larger
      study assessing long-term adjustment in survivors of childhood cancer, 40 males
      and 27 females (mean age = 19.69 years, SD = 3.87) completed the BII and two
      validation measures: the SF-36 health survey and the Perceived Illness Experience
      measure. RESULTS: The five BII subscales--General Appearance, Body Competence,
      Others' Reaction to Appearance, Value of Appearance, and Body Parts--exhibited
      moderate to high internal reliability and concurrent validity. No significant sex
      differences in body image emerged, nor was age at diagnosis or time since
      diagnosis significantly correlated with body image. CONCLUSIONS: The measure may
      be of value in clinical settings, where it could be used to identify adjustment
      problems related to body image disturbance in pediatric cancer patients.

PMID- 9585641
TI  - Brief report: behavioral correlates of postoperative pain in toddlers and
      preschoolers.
AB  - OBJECTIVE: To investigate the association between preoperative parent and child
      behaviors and postoperative pain in toddlers and preschoolers. METHOD:
      Participants were 74 pediatric patients (59 boys, 15 girls), scheduled for
      inguinal hernia or hydrocele repair, and their parents. Children ranged in age
      from 12 to 64 months (M = 33.7 months, SD = 14.7 months). Child and parent
      behaviors were assessed 30 minutes prior to surgery using the Behavioral
      Observation Scale (BOS), a modified version of the Dyadic Prestressor Interaction
      Scale (Melamed & Bush, 1985. Postoperative pain was assessed using an
      observational measure, the Toddler-Preschooler Postoperative Pain Scale (TPPPS)
      (Tarbell, Cohen, & Marsh, 1992). RESULTS: Postoperative pain was negatively
      related to parents' provision of surgery-relevant information during the
      preoperative observation period. CONCLUSIONS: Preoperative interventions for
      young children should include information about the surgery experience.

PMID- 9585642
TI  - Debugging psychiatry.

PMID- 9585643
TI  - Developmental contributions to comorbidity?

PMID- 9585644
TI  - Language impairments and psychopathology.

PMID- 9585645
TI  - Compulsive compliance in a young maltreated child.

PMID- 9585646
TI  - Laboratory and diagnostic testing in child and adolescent psychiatry: a review of
      the past 10 years.
AB  - OBJECTIVE: To review in a critical fashion the literature of the past decade
      covering diagnostic and laboratory testing in the field of child and adolescent
      psychiatry. METHOD: A computerized search of articles published during the past
      decade was made, and selected articles are presented. Because of the paucity of
      articles specifically relating to minors, selected articles from adult psychiatry
      are cited. RESULTS: With a few notable exceptions, few controlled studies on the
      specificity and sensitivity of any laboratory test for any specific disorder of
      behavior presenting in children have been conducted in children and adolescents.
      A high index of suspicion will remain the clinician's best ally in utilizing
      laboratory measures in the assessment of psychopathology. Nonetheless, studies
      have appeared that will guide the clinician as to what tests are not clinically
      useful. CONCLUSION: Indications and the lack of indications for specific
      laboratory studies are an integral part of the knowledge base that child
      psychiatrists must have. Much more empirical data will need to be collected
      prospectively to inform the field and to move the judicious use of the laboratory
      from an art to a science.

PMID- 9585647
TI  - Suicide among children and younger and older adolescents in Norway: a comparative
      study.
AB  - OBJECTIVE: To compare characteristics and risk factors of suicide in early
      adolescence (younger than age 15 years) and in late adolescence. The authors
      examined whether differences in risk factors or resilience might explain the
      different suicide rates in the two age groups. METHOD: Information about all
      registered suicides of young people in Norway from 1990 through 1992 was gathered
      from several professional informants. Children younger than 15 years old who
      committed suicide (n = 14) were compared with late-adolescent suicides (15
      through 19 years) (n = 115) and with controls (n = 889). RESULTS: Younger
      compared with older adolescent suicides more often hanged themselves (93% versus
      35%). Suicidal ideation (7% versus 39%) and precipitating events were described
      less frequently (29% versus 49%). Older adolescents more often had psychiatric
      disorders (77% versus 43%). Compared with controls, the risk factors for suicide
      were affective disorders (young adolescents: odds ratio [OR] = 23.8, 95%
      confidence interval [CI] = 2.3 to 1,183; older adolescents: OR = 19.6, CI = 10.6
      to 38.8); disruptive disorders (young adolescents: OR = 3.4, CI = 0.0 to 340;
      older adolescents: OR = 6.1, CI = 3.0 to 12.7); and not living with two
      biological parents (young adolescents: OR = 3.1, CI = 0.6 to 14.7; older
      adolescents: OR = 2.5, CI = 1.6 to 3.8). CONCLUSION: Children and young
      adolescents completing suicide were less exposed to known risk factors than older
      adolescents. The increased suicide risk was similar for both groups when they
      were compared with community controls. The low suicide incidence in childhood may
      be related to fewer risk factors, rather than to resilience to risk factors.

PMID- 9585648
TI  - Psychiatric and injury prevention approaches to youth suicide: questions,
      answers, and lethal means.

PMID- 9585650
TI  - Association between multiple suicide attempts and negative affects in
      adolescents.
AB  - OBJECTIVE: To compare the level of negative emotions-anxiety, depression,
      aggression, and impulsivity-in hospitalized adolescents with a history of either
      a single or multiple suicide attempts. METHOD: Thirty-two adolescents
      hospitalized for a first suicide attempt, 19 hospitalized for a repeated attempt
      (fifth or more), 109 nonsuicidal psychiatric inpatients, and 85 community
      controls were assessed for level of depression, anxiety, aggression, and
      impulsivity with the Beck Depression Inventory, the State-Trait Anxiety
      Inventory, the Multidimensional Anger Inventory, and the Suicide Potential Scale.
      RESULTS: Both suicidal groups demonstrated higher levels of most of the negative
      emotions than both the normal controls and the nonsuicidal inpatients. When the
      first attempters were compared with the multiple attempters, similarly high
      levels were noted for most dimensions of anxiety and depression. A trend toward
      increased aggression was noted among the multiple suicide attempters on all
      parameters evaluated; some of these differences were significant. CONCLUSION: In
      already highly anxious and depressed suicidal inpatients, a high level of
      aggression might significantly increase the risk of recidivism.

PMID- 9585649
TI  - Suicide in youth: a public health framework.

PMID- 9585652
TI  - Psychiatric contacts among youths aged 13 through 24 years who have made serious
      suicide attempts.
AB  - OBJECTIVE: To compare the history of psychiatric contacts among young people who
      have made medically serious suicide attempts and control subjects. METHOD: Using
      a case-control design, the authors contrasted 129 young people who made serious
      suicide attempts with 153 randomly selected community controls on a series of
      measures of lifetime, prior year, and prior month contacts with psychiatric
      services. RESULTS: Of those who made serious suicide attempts, 78.3% had a
      lifetime history of contact with health services for psychiatric reasons, 72.1%
      reported contact within the year preceding the suicide attempt 58.9% reported
      contact within the month preceding the suicide attempt, and 29.5% had a lifetime
      history of psychiatric hospital admission. Within the year preceding the suicide
      attempt, 21.7% had been admitted to a psychiatric hospital and 67.4% had
      outpatient consultations for psychiatric problems. Multiple logistic regression
      suggested that the best psychiatric service predictors of risk of serious suicide
      attempt were admission within the preceding year (p < .005) and outpatient
      consultation within the preceding month (p < .0001). CONCLUSIONS: Young people
      making serious suicide attempts had vastly elevated rates of a range of
      psychiatric contacts including hospital admissions and outpatient consultations.
      These findings imply that the development of improved treatment and management
      strategies for young people with psychiatric morbidity may be a very effective
      approach to reducing youthful suicidal behaviors.

PMID- 9585651
TI  - Prediction of major depression and dysthymia from CES-D scores among ethnic
      minority adolescents.
AB  - OBJECTIVE: The Native Hawaiian Mental Health Research Development Program is an
      epidemiological longitudinal study of adolescents residing in Hawaii. This
      article examines the utility of the Center for Epidemiologic Studies-Depression
      Scale (CES-D) for predicting DSM-III-R diagnoses of major depression (MD) and
      dysthymic disorder (DD) and investigates whether prediction differs by gender and
      ethnicity. METHOD: Diagnostic Interview Schedule for Children interviews were
      conducted with 556 adolescents randomly selected from among more than 7,000
      students who had completed the CES-D. RESULTS: Six-month prevalence rates were as
      follows: MD = 8.5%, DD = 4.7%, either (MDDD) = 9.9%. Prevalence rates were
      significantly higher among females, but after CES-D scores were accounted for,
      gender no longer predicted depression in most analyses. When a cutoff score of 16
      was used, classification accuracy was lower for Native Hawaiians than non
      Hawaiians. However, after group differences in gender and grade level were
      accounted for, the predictive validity of the CES-D did not differ by ethnicity.
      CES-D factor 1 scores identified MD, DD, and MDDD about as well as the total
      score or all three factors together. CONCLUSIONS: These results support the
      validity of the CES-D for screening for depression among adolescents of Native
      Hawaiian and other minority backgrounds.

PMID- 9585653
TI  - Randomized trial of a home-based family intervention for children who have
      deliberately poisoned themselves.
AB  - OBJECTIVE: To establish whether an intervention given by child psychiatric social
      workers to the families of children and adolescents who had attempted suicide by
      taking an overdose reduced the patients' suicidal feelings and improved family
      functioning. METHOD: One hundred sixty-two patients, aged 16 or younger, who had
      deliberately poisoned themselves were randomly allocated to routine care (n = 77)
      or routine care plus the intervention (n = 85). The intervention consisted of an
      assessment session and four home visits by the social workers to conduct family
      problem-solving sessions. The control group received no visits. Both groups were
      assessed at the time of recruitment and 2 and 6 months later. The primary outcome
      measures were the Suicidal Ideation Questionnaire, the Hopelessness Scale, and
      the Family Assessment Device. RESULTS: There were no significant differences in
      the primary outcomes between the intervention and control groups at either of the
      outcome assessments. Parents in the intervention group were more satisfied with
      treatment (mean difference 1.4 [95% confidence interval 0.6 to 2.1]). A subgroup
      without major depression had much less suicidal ideation at both outcome
      assessments (analysis of covariance p < .01) compared with controls. CONCLUSIONS:
      The home-based family intervention resulted in reduced suicidal ideation only for
      patients without major depression.

PMID- 9585656
TI  - Psychiatric illness and family support in children and adolescents with diabetic
      ketoacidosis: a controlled study.
AB  - OBJECTIVE: To compare compliance, psychiatric disorders, and family support in
      children with insulin-dependent diabetes mellitus (IDDM) hospitalized with
      diabetic ketoacidosis (DKA) and clinic controls. METHOD: Twenty-five youths
      hospitalized with DKA and 25 matched outpatient subjects with IDDM with no
      history of DKA during the preceding year were assessed cross-sectionally, using
      the Diagnostic Interview Schedule for Children, measures of general and diabetes
      specific family functioning, and measures of self-esteem and social competence.
      Levels of glycosylated hemoglobin and information about compliance with the
      treatment regimen were obtained. RESULTS: A significantly higher number of
      psychiatric disorders was observed in the hospitalized children, with 88% meeting
      criteria for at least one disorder (versus 28% of controls). Self-esteem and
      social competence were lower in the hospitalized group, and their families scored
      lower on problem-solving and diabetes-specific "warmth-caring." CONCLUSIONS:
      Children with recurrent DKA may be at greater risk of associated psychopathology
      than diabetic controls with no such history. DKA children's reports of
      noncompliance may be more sensitive than their parents' reports, and their
      families may lack warm, caring parent-child relationships.

PMID- 9585655
TI  - Randomized, controlled trial of amitriptyline versus placebo for adolescents with
      "treatment-resistant" major depression.
AB  - OBJECTIVE: To assess the response to a serotonergic/noradrenergic tricyclic
      antidepressant, amitriptyline (AMI), in a group of adolescents with treatment
      resistant major depressive disorder (MDD). METHOD: Twenty-seven depressed
      adolescents admitted to a state hospital underwent a 10-week randomized,
      controlled trial with a flexible dose of AMI or placebo. RESULTS: There were no
      differences between patients taking AMI (n = 13) and placebo (n = 14). Both
      treatment groups showed approximately 70% to 80% improvement on the clinical
      outcome measurements, and 65% to 70% showed functional improvement. At the end of
      the protocol, 30% of patients still fulfilled criteria for MDD and had impaired
      functioning. Patients taking AMI experienced significantly more dry mouth and
      tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels
      were 226.2 ng/mL +/- 80.8 ng/mL. CONCLUSIONS: No significant differences were
      found between AMI and placebo, in part because of the high placebo response rate.
      Although both treatment groups showed substantial response, at the end of
      treatment a substantial proportion of patients still had MDD of subsyndromal
      symptoms of depression. This and other studies of tricyclic antidepressants
      question the use of this medication as first-line treatment for youths with MDD.

PMID- 9585654
TI  - Analog classroom assessment of Adderall in children with ADHD.
AB  - OBJECTIVE: This was a randomized, double-blind, crossover study of 30 children
      with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time
      course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive
      control (placebo), and a positive control (clinical dose of methylphenidate).
      METHOD: For each treatment condition, a capsule was administered in the morning
      and assessments were performed in an analog classroom setting every 1.5 hours
      across the day. Subjective (teacher ratings of deportment and attention) and
      objective (scores on math tests) measures were obtained for each classroom
      session, and these measures were used to evaluate time-response and dose response
      effects of Adderall. RESULTS: For doses of Adderall greater than 5 mg,
      significant time course effects were observed. Rapid improvements on teacher
      ratings and math performance were observed by 1.5 hours after administration, and
      these effects dissipated by the end of the day. The specific pattern of time
      course effects depended on dose: the time of peak effects and the duration of
      action increased with dose of Adderall. CONCLUSIONS: This documentation of
      efficacy in a controlled study supports the addition of Adderall to the
      armamentarium of psychotropic medications for the treatment of ADHD. The
      differences in time-response patterns of Adderall and methylphenidate may help
      tailor treatment to meet specific clinical needs of different children with ADHD.

PMID- 9585657
TI  - Young children's adjustment to chronic family adversity: a longitudinal study of
      low-income families.
AB  - OBJECTIVE: To test the relation between multiple family stressors and young
      children's adjustment problems. METHOD: Longitudinal data were collected on 300
      low-income, ethnically diverse, male subjects beginning during infancy and
      followed until age 31/2. RESULTS: General support was found for the family
      stressor hypothesis. Stressor groups at 18 and 24 months predicted Child Behavior
      Checklist Externalizing and Internalizing factors at 24 and 42 months, including
      clinically elevated problems. CONCLUSIONS: The results confirm and extend
      previous investigation of the family stressor hypothesis. They suggest that
      psychological evaluations of young children need to be ecologically based,
      including intra- and extrafamilial factors that appear to cumulatively increase
      risk of behavior problems.

PMID- 9585658
TI  - Case study: when restraints are the least restrictive alternative for managing
      aggression.
AB  - This article discusses the controversial use of restraints with a persistently
      violent adolescent on a child and adolescent psychiatry unit. The authors present
      an individualized program that used a series of ambulatory restraints on a long
      term basis and prophylactically to contain the aggression of a psychotic girl.
      Clozapine was used concomitantly to control her psychosis. The prophylactic use
      of mechanical restraints allowed this teenager to be integrated into the milieu
      and to receive multiple treatments that the standard protocol precluded. This
      case underscores the difficulties in managing aggression when youths do not
      respond to standard protocols and do not conform to our assumptions about the
      least restrictive alternative. It is concluded that prophylactic mechanical
      restraint provided the least restrictive alternative to personal freedom for this
      teenager and had therapeutic benefit.

PMID- 9585659
TI  - Children and computers: risks and benefits.

PMID- 9585660
TI  - Development of the cerebral cortex: V. Transcription factors and brain
      development.

PMID- 9585661
TI  - The Drug Evaluation Classification Program: using ocular and other signs to
      detect drug intoxication.
AB  - BACKGROUND: A systematic approach to determining drug intoxication has been
      developed for use by police officers. By considering specific physiological
      signs, trained officers can detect the effects of seven major drug types.
      METHODS: Officers follow a 12-step testing sequence and evaluate signs such as
      pupil sizes and responses, eye movements, heart rate, body temperature, mental
      timing, and balance. A matrix is then used to compare that subject's signs to
      those that would be produced by the seven types of drugs. If a pattern match is
      found, the officer concludes that the subject is under the influence of a drug
      and specifies the drug type. RESULTS: Several field and laboratory validation
      studies have been conducted using these procedures. In general, officers were 70%
      to 90% accurate in determining intoxication status and drug classification, but
      poly-drug use and drug rebound effects can sometimes cause problems in
      interpretation. CONCLUSION: Ocular and other physiological signs can be used to
      detect drug intoxication and classify the type of drug taken. Knowledge of the
      procedures used in the Drug Recognition Program can enable optometrists to serve
      as consultants to the police and as expert witnesses in cases involving the use
      of ocular signs that indicate illicit drug use.

PMID- 9585662
TI  - Skin cancer and actinic keratoses.
AB  - BACKGROUND: Skin cancer is the most common cancer among whites and is increasing
      faster than most other cancers. Non-melanoma skin cancers are typically slow
      growing, but in the periocular region they are more aggressive. If not treated
      early, malignant melanoma is almost always lethal. Optometrists can play an
      important role in the early detection of skin cancer. METHODS: One thousand
      (1,000) consecutive patients, ages 35 and older, were screened for skin cancer
      and actinic keratoses of the head and neck. Patients were also questioned for any
      previous diagnoses for these conditions. The screenings were done as part of an
      optometric examination in a private practice in southeastern Pennsylvania.
      RESULTS: Ninety-six (96) white patients had a previous diagnosis of skin cancer
      or actinic keratoses. Three additional patients were diagnosed with one of these
      conditions as part of this study. From this total of ninety-nine (99) positive
      patients, all had skin cancer-except three (3), who had actinic keratoses. Of the
      white patients, 10.3% were positive, none of the 41 blacks nor the one Asian had
      any history. More males reported these conditions than females (12.8% vs. 8.6).
      The head and neck was the most common site reported (69.7%). CONCLUSION: A large
      number of white patients in this primary care optometric practice were positive
      for skin cancer or actinic keratosis. Optometrists should seriously consider
      screening the exposed skin of their older white patients.

PMID- 9585663
TI  - Spontaneous enophthalmos associated with asymptomatic maxillary sinus disease
      (silent sinus syndrome): case report.
AB  - BACKGROUND: Cases of spontaneous enophthalmos (in otherwise asymptomatic
      patients) that are unrelated to trauma, surgery, or systemic disease have been
      reported infrequently in the literature. CASE REPORT: We present a 41-year-old
      patient who demonstrated this recently reported constellation of findings
      referred to as silent sinus syndrome. CONCLUSION: Consideration should be given
      to the causes of spontaneous and acquired enophthalmos and the possibility of
      silent sinus syndrome. Other causes of enophthalmos based on the clinical
      features should also be considered.

PMID- 9585664
TI  - Pharmaceutical practice management.
AB  - BACKGROUND: Being accomplished in the short span of 21 years the number of states
      granting therapeutic optometric privileges has now reached 50. Since health care
      reform is also expanding, optometrists' prescribing responsibilities will
      probably increase in proportion to their clinical demands. PURPOSE: In addition
      to clinical expertise, optometrists should possess practical knowledge about
      pharmaceutical industry practices and the effects of managed care. This article
      addresses issues such as drug pricing and distribution, reimbursement, and
      patient costs, which can affect pharmaceutical dispensing. CONCLUSION:
      Optometrists should become aware of "nonclinical" prescribing influences that can
      affect patients. By doing so, they can make informed decisions about the products
      they prescribe, to ensure optimum patient care and compliance.

PMID- 9585665
TI  - Prevalences of ocular conditions among Hispanic, white, Asian, and black
      immigrant students examined by the UCLA Mobile Eye Clinic.
AB  - BACKGROUND: First-and second-generation immigrant children are the fastest
      growing component of the U.S. population under 15 years of age. Prevalences of
      ocular conditions in first-generation immigrant children are described,
      stratified by ethnicity and sex, and compared to previous UCLA Mobile Eye Clinic
      (MEC) studies and the National Health and Nutrition Examination Surveys. METHODS:
      Clinical data from 2,229 newly immigrated students, ages 8 to 16 years of age,
      examined by the UCLA Mobile Eye Clinic from 1990-1996, were analyzed by chi
      squares test. RESULTS: Females have significantly higher prevalences of
      astigmatism (p = 0.003) and myopia (p = 0.001) than males. Asians have
      significantly higher prevalences of myopia (p < 0.001) and visual acuity worse
      than 20/40 without correction (p < 0.001) than Hispanics. CONCLUSIONS: Overall
      ocular health of this sample is very close to that of age-matched U.S. children,
      but with markedly lower prevalences of extraocular muscle imbalance and color
      vision deficiencies. Examiners should be aware of the higher rate of astigmatism
      and myopia in first-generation female immigrants, as well as the higher
      prevalence of myopia among Asians.

PMID- 9585666
TI  - Relation of childhood myopia progression rates to time of year.
AB  - BACKGROUND: One potential method for assessment of the effect of near work on
      childhood myopia progression is to compare progression rates overtime spans that
      have differing near-point demands. METHODS: Myopia progression rates were
      calculated for a 6-month period during the school year (called school rate in
      this article) and for a 6-month period that included the 3 months of summer
      vacation (called summer rate). Data used for analysis were right eye spherical
      equivalents from manifest subjective refractions of 27 children in a longitudinal
      study at Northeastern State University in Oklahoma, and 15 children in a
      longitudinal study at Indiana University. All subjects wore single-vision
      spectacle lenses. RESULTS: The mean summer rate for the 42 subjects was -0.39
      diopters per year (D/yr) (SD = 0.46). The mean school rate was -0.72 D/yr (SD =
      0.57). The rates during the two periods were significantly different by two
      tailed paired t-test (p = 0.006). CONCLUSIONS: The differing amount of nearpoint
      activity during the school year and the summer is a potential explanation for the
      different rates of myopia progression during those two time periods.

PMID- 9585668
TI  - From the operating room to the laboratory.

PMID- 9585669
TI  - Perspective: AAMP, now more than ever. Association for Academic Minority
      Physicians.

PMID- 9585670
TI  - Improved social and language skills after secretin administration in patients
      with autistic spectrum disorders.
AB  - We report three children with autistic spectrum disorders who underwent upper
      gastrointestinal endoscopy and intravenous administration of secretin to
      stimulate pancreaticobiliary secretion. All three had an increased
      pancreaticobiliary secretory response when compared with nonautistic patients
      (7.5 to 10 mL/min versus 1 to 2 mL/min). Within 5 weeks of the secretin infusion,
      a significant amelioration of the children's gastrointestinal symptoms was
      observed, as was a dramatic improvement in their behavior, manifested by improved
      eye contact, alertness, and expansion of expressive language. These clinical
      observations suggest an association between gastrointestinal and brain function
      in patients with autistic behavior.

PMID- 9585671
TI  - The risk for recurrence of premature births to African-American and white women.
AB  - Preterm birth rates are higher for African Americans than for whites, but the
      risk for recurrence is not well defined. We tested the hypothesis that the base
      and recurrence rates for premature births are higher for African Americans than
      for whites. We recruited a cohort of African-American and white women giving
      birth to singleton infants between 1988 and 1993 at Perinatal Network, a Midwest
      urban teaching hospital. These women had known reproductive history, delivered
      two or more singletons, and had no planned abortions, miscarriages, or induced
      preterm labor. Premature infants were born at less than 37 completed weeks of
      gestation. The total preterm birth rate among African Americans was 24.5%,
      significantly higher than the 11.1% for whites (relative risk, 2.22; confidence
      interval, 1.79 to 2.75). The preterm birth rate among African Americans for the
      second pregnancy was 30.6%, significantly higher than the rate of 18.2% for the
      first pregnancy and 24.5% for the third and fourth pregnancies. The preterm birth
      rates for whites were 11.7% for the first pregnancy, 9.8% for the second, and
      12.9% for the third and fourth pregnancies, which were not significantly
      different from each other. Considering only the first two pregnancies, recurrence
      accounted for 32.6% of all premature births for both African Americans and
      whites. After the second pregnancy, 68% of African-American and 41.7% of white
      premature babies were born to women who had previous preterm infants. We conclude
      that preterm births are relatively common for African Americans and whites in the
      first two pregnancies. Women, particularly African-American women with a previous
      preterm birth at either the first or second pregnancy, require more specific
      management to prevent recurrence of preterm birth.

PMID- 9585672
TI  - Recurrent central diabetes insipidus secondary to cryptococcal meningitis.
AB  - Meningitis is often associated with hyponatremia due to inappropriate secretion
      of antidiuretic hormone, and diabetes insipidus is associated with bacterial
      meningitis. This article describes a patient with acquired immunodeficiency
      syndrome who experienced recurrent episodes of central diabetes insipidus in
      association with recurrent fungal meningitis. Desmopressin was effective in
      controlling the polyuria until the episodes of meningitis resolved.

PMID- 9585673
TI  - Polymorphisms of the apolipoprotein B 3' variable number of tandem repeats region
      associated with coronary artery disease in Taiwanese.
AB  - We studied the allelic frequency of the variable number of tandem repeats region
      3' of the apolipoprotein B gene (apoB 3' VNTR) and its impact on coronary artery
      disease (CAD) in 150 patients with CAD and 153 normal controls in a Taiwan
      population. apoB 3' VNTR alleles were classified according to the number of
      repeats of a 15-bp hypervariable elements (HVE), the sequence of which was
      determined using the polymerase chain reaction and direct sequencing. Thirteen
      alleles comprising from 26 to 54 HVEs were identified. The CAD patients had
      greater heterozygosity (0.58 vs 0.42) and a higher frequency of long (> 36-HVE)
      apoB 3' VNTR alleles than the controls (18.7% vs 10.8%, p < 0.01). CAD patients
      with two HVE-36 alleles and no HVE-32 alleles (the two most common forms) had
      significantly higher concentrations of LDL-cholesterol, apolipoprotein B, and
      triglycerides, and significantly lower values of HDL-cholesterol and
      apolipoprotein AI than the control group (p < 0.01 for all comparisons). The
      length of the apoB 3' VNTR was not correlated with the plasma concentrations of
      any of the lipids. We conclude that long apoB 3' VNTR alleles occur more
      frequently in CAD patients, but that apoB 3'VNTR genotypic variation has little
      impact on the risk of dyslipidemia in Taiwanese.

PMID- 9585674
TI  - Etiology, timing of insult, and neuropathology of cerebral palsy evaluated with
      magnetic resonance imaging.
AB  - To define the patterns of pathologic changes in cerebral palsy (CP) and to assess
      the etiology and time of brain damage, we reviewed the magnetic resonance images
      and clinical records of 86 pediatric CP patients seen over 8 years. Patients were
      divided into two groups, based on the gestational age at birth. The majority of
      CP patients (69) had spasticity. In the premature group (< 37 wk gestational age)
      n = 27), spastic diplegia (12 patients) and quadriplegia (8) were the major
      subtypes. In the term group (> or = 37 wk gestational age) ( n = 59), spastic
      hemiplegia (23) and quadriplegia (12) were most common. The other main clinical
      manifestations in the two groups were seizures (36) and mental retardation (15).
      Magnetic resonance (MR) imaging provided significant findings in 82 patients
      (95%). In the 27 patients born prematurely, MR imaging revealed periventricular
      leukomalacia (17), multicystic encephalomalacia (3), cortical and subcortical
      atrophy (4), migration disorders (2), and basal ganglia injury (1). Among the
      patients born at term, the MR imaging findings were more heterogeneous; they
      included cortical and subcortical atrophy (17), brain malformations (17),
      periventricular leukomalacia (6), multicystic encephalomalacia (5), porencephaly
      (4), hemiatrophy (3), delayed myelination (3), and none (4). MR imaging alone
      could define the time of brain insults in 73 of our 86 CP patients. Combined with
      clinical histories, MR imaging could help assess the time of insult in 93% of
      patients. The brain insults occurred prenatally in 34 of our patients,
      perinatally in 37, and postnatally in eight. The time of insult could not be
      determined in six patients. In the premature patients, the insult occurred most
      frequently perinatally (74%), whereas in the term group it occurred most
      frequently prenatally (54%). MR imaging was found to be very helpful in the
      evaluation of the various neuropathologic changes in CP, in the depiction of the
      etiology, and in the determination of the time of brain injury.

PMID- 9585675
TI  - Extent of collateral sprouting of intact nerve fibers in rats depends on the
      local availability of nerve growth factor.
AB  - We investigated the influence of local administration of anti-nerve growth factor
      (NGF) serum on collateral nerve fiber sprouting caused by chronic constriction
      injury (CCI) of the sciatic nerve in rats. CCI was induced in adult Sprague
      Dawley rats (six per group) by constriction of the sciatic nerve of the right
      hind limb. Control rats received no further manipulation. In four other groups,
      rabbit preimmune (control) serum or low (18 ng) or high (1800 ng) doses of anti
      NGF serum were injected into the operated or unoperated hind limb each day for 1
      month. We used an Evans dye-labeled plasma extravasation technique to visualize
      the extent of collateral sprouting. Local injection of anti-NGF serum at both
      high and low doses, but not control serum, significantly reduced the spread of
      collateral sprouting from the saphenous nerve into the sciatic nerve innervation
      territory. High-dose anti-NGF serum did not block collateral sprouting when
      injected into the contralateral (unoperated) hind limb, indicating that the
      inhibition of sprouting was not caused by a systemic effect. In conclusion, local
      administration of anti-NGF serum can block sprouting of collateral fibers after
      nerve injury. Our findings suggest that collateral sprouting is dependent on the
      local availability of NGF to nearby intact cutaneous nerve fibers.

PMID- 9585677
TI  - Radiographic and computed tomographic findings of gastric mucosa-associated
      lymphoid tissue lymphomas.
AB  - The purpose of this retrospective study was to evaluate the detection of gastric
      mucosa-associated lymphoid tissue (MALT) lymphoma lesions by upper
      gastrointestinal (UGI) radiography and computed tomography (CT). Fifteen patients
      with endoscopic biopsy-proven MALT lymphoma were included. Fourteen of these
      patients underwent double-contrast UGI radiography and 14 were examined with CT
      of the upper abdomen; 13 underwent both procedures. UGI radiography identified
      88% (30/34) of lesions detected by endoscopy, including 12 of 13 enlarged rugal
      folds and 15 of the 17 multinodular lesions, but failed to identify two of the
      three ulcerative lesions. UGI radiography identified the only submucosal lesion
      demonstrated by endoscopy, as well as one at the gastric antrum that had been
      missed by endoscopy. CT demonstrated nine of 30 endoscopically proven MALT
      lymphoma lesions, three with focal thickening of the gastric wall and six with a
      lobulated inner gastric wall. CT failed to demonstrate two fundal and 19 antral
      or gastric body lesions. Our findings suggest that the predominant UGI features
      of gastric MALT lymphoma are enlarged folds and multinodular lesions. Although
      UGI radiography does not reveal all MALT lymphoma lesions, it may find lesions
      that are not detected by endoscopy. Mucosal lesions of gastric MALT lymphoma are
      usually not detected by CT.

PMID- 9585676
TI  - Allogeneic peripheral blood stem cell transplantation and early detection of
      donor engraftment by polymerase chain reaction.
AB  - Patients with hematologic malignancy or severe aplastic anemia after
      myeloablative chemo- and radiotherapy were given granulocyte colony-stimulating
      factor (G-CSF)-mobilized, cryopreserved allogeneic peripheral blood stem cells
      (PBSCs) from 15 healthy donors who were either human leukocyte antigen (HLA)
      matched siblings (n = 13) or haploidentical offspring (2). Polymerase chain
      reaction-amplified short tandem repeat genotyping was used for early confirmation
      of donor engraftment after PBSC transplantation (PBSCT). A standard cyclosporine
      A/methotrexate combination was used to prevent acute graft-versus-host disease
      (GVHD). All donors, including one in the third trimester of pregnancy, tolerated
      G-CSF administration and 3-day PBSC harvesting procedures well. Engraftment was
      prompt for all patients; it was verified using a panel of 12 human polymorphic
      short tandem repeat loci from bone marrow as early as 7 days posttransplantation.
      This status was maintained until relapse, when mixed chimerism was detected using
      the polymerase chain reaction. A minimum resurgence of recipient cells to 1% of
      the population was required to detect chimerism. The median times to recovery of
      the absolute neutrophil count to greater than 0.5 x 10(9)/L and the sustained
      platelet count to greater than 20 x 10(9)/L without transfusion were 10 and 12
      days after PBSCT, respectively. Six patients experienced acute GVHD, Grade I in
      two patients and Grade II in four, including two HLA-haploidentical recipients.
      Chronic GVHD was noticed in three of the 11 patients who were followed for at
      least 100 days after PBSCT. Ten patients were still alive at the latest follow-up
      and have been disease free for a median of 278 days (range 60-671). Five patients
      died from causes other than graft failure: three from leukemia relapse and two
      from transplant-related complications. The results confirm that G-CSF can be
      safely administered to healthy donors and that engraftment after allogeneic PBSCT
      is fast and durable. Complete chimerism can be detected early by genomic
      analysis. PBSCT may offer an alternative to bone marrow transplantation.

PMID- 9585678
TI  - One-week proton pump inhibitor-based triple therapy eradicates residual
      Helicobacter pylori after failed dual therapy.
AB  - The purposes of this study were to assess the efficacy of a 1-week proton pump
      inhibitor (PPI)-based triple therapy after failure of dual therapy in
      Helicobacter pylori eradication, and to compare the effectiveness of
      clarithromycin and metronidazole in this regimen. Between January 1996 and March
      1997, 67 patients with persistent H. pylori infection after a 2-week course of
      dual therapy (amoxicillin plus omeprazole) were enrolled. They were randomly
      assigned to receive amoxicillin (1000 mg twice daily) and omeprazole (20 mg twice
      daily) plus either metronidazole (500 mg twice daily) or clarithromycin (250 mg
      twice daily). Endoscopy was performed in each patient to assess the status of H.
      pylori using the rapid urease test (CLOtest) and the histologic findings before
      dual therapy, after dual therapy, and after triple therapy. H. pylori isolates
      were tested for antibiotic resistance when triple therapy failed. The 1-week
      triple therapy was well tolerated in both groups with no adverse effects severe
      enough to cause withdrawal from the trial. Residual H. pylori was eradicated in
      94% (33/35) of patients in the clarithromycin group and 84% (27/32) in the
      metronidazole group; the difference was not statistically significant. All seven
      patients in whom triple therapy failed were infected with metronidazole-resistant
      isolates and two also had clarithromycin-resistant isolates. This 1-week triple
      therapy is safe and effective in eradicating residual H. pylori after dual
      therapy failure. Failure of the rescue regimen is related to antimicrobial agent
      resistance. Because of the high metronidazole resistance rate in Taiwan,
      clarithromycin appears to be more promising than metronidazole for the control of
      H. pylori.

PMID- 9585679
TI  - Respiratory mechanics before and after hemodialysis in mechanically ventilated
      patients.
AB  - Hemodialysis, which leads to negative fluid balance, is often required in
      mechanically ventilated patients with renal failure. We conducted a prospective
      study on the influence of hemodialysis on the respiratory mechanics in 14
      mechanically ventilated patients (10 men, 4 women, mean age 70.1 +/- 8.1 yr) with
      various causes of renal failure requiring hemodialysis in an intensive care unit.
      Respiratory mechanics were measured before and after hemodialysis using the
      interrupter technique under constant flow and constant volume. The values of
      several parameters of respiratory mechanics were significantly lower after
      hemodialysis: peak airway pressure (26.97 +/- 4.62 vs 23.45 +/- 4.13 cmH2O),
      airway pressure at zero flow (23.81 +/- 4.18 vs 21.50 +/- 3.79 cmH2O), airway
      plateau pressure (18.56 +/- 3.70 vs 16.48 +/- 3.07 cmH2O), and intrinsic positive
      end-expiratory pressure (4.03 +/- 2.90 vs 2.65 +/- 1.84 cmH2O). Minimal
      respiratory resistance and maximal respiratory resistance were significantly
      decreased after hemodialysis (4.38 +/- 1.26 vs 2.99 +/- 1.00 cmH2O/L/s and 9.93
      +/- 2.50 vs 8.39 +/- 2.43 cmH2O/L/s, respectively), but effective additional
      respiratory resistance and static respiratory compliance were not. Significant
      correlations were found between body weight reduction by hemodialysis and changes
      in minimal respiratory resistance (r = 0.758, p < 0.01), maximal respiratory
      resistance (r = 0.544, p < 0.05), and static respiratory compliance (r = 0.703, p
      < 0.01). We conclude that hemodialysis significantly alters the respiratory
      mechanics in mechanically ventilated renal failure patients and that the
      alteration may be related to the negative fluid balance caused by hemodialysis.

PMID- 9585680
TI  - Short-course chemotherapy for isoniazid-resistant pulmonary tuberculosis.
AB  - Standard short-course chemotherapy including isoniazid, rifampicin, pyrazinamide,
      and ethambutol has been the recommended treatment for tuberculosis in Taiwan
      since November 1990. The effectiveness of this treatment was evaluated
      retrospectively in 108 patients with isolates resistant to isoniazid alone and
      115 patients with drug-susceptible pulmonary tuberculosis diagnosed and treated
      at the Taiwan Provincial Chronic Disease Control Bureau from November 1990
      through December 1995. The success rate of treatment was 94.4% in patients with
      isoniazid-resistant Mycobacterium tuberculosis strains, which was not
      significantly different from the 97.4% rate in patients with susceptible strains.
      Of the patients treated successfully, no bacteriologic relapse was found in 97
      patients with isoniazid-resistant strains or 103 patients with drug-susceptible
      strains 12 months after the end of chemotherapy. No significant advantage in
      treatment outcome was found in patients infected with isoniazid-resistant strains
      who received chemotherapy for more than 6 months (successful treatment rate,
      95.0% vs 92.8%), but the failure rate was higher in patients with a previous
      history of antituberculosis therapy (17.6% vs 3.3%). We conclude that short
      course chemotherapy is effective for isoniazid-resistant pulmonary tuberculosis
      and that there is no significant difference in treatment outcome between patients
      with or without isoniazid-resistant disease.

PMID- 9585681
TI  - Successful resection of sigmoid colon cancer in a patient with factor XI
      deficiency.
AB  - A 42-year-old-women with sigmoid colon adenocarcinoma was found to have isolated
      prolonged activated partial thromboplastin time (aPTT 102.5 s, normal range 24-36
      s) preoperatively. Her medical history included an episode of prolonged
      postdelivery uterine bleeding 16 years previously. A mixed aPTT test showed
      immediate correction of the prolonged aPTT, indicating a coagulation factor
      deficiency in the intrinsic pathway. Factor assays showed factor XI was below 1%
      of average normal value whereas factor VIII, IX and XII activities were normal.
      Family screening revealed one sister among the three siblings also had isolated
      prolonged aPTT. The patient was transfused with four units (5mL/kg) of fresh
      frozen plasma the day before surgery, then with two units during surgery. The
      operation was uneventful with no bleeding problems. The patient recovered
      smoothly and is currently undergoing adjuvant chemotherapy. This is the first
      formal report of a patient with factor XI deficiency undergoing major surgery in
      Taiwan. Careful monitoring of aPTT, with fresh frozen plasma transfusion, when
      needed, may safely overcome bleeding problems during surgery.

PMID- 9585682
TI  - Hypothermia predisposing to Pseudomonas putida sepsis in a child with
      panhypopituitarism.
AB  - A 14-year-old boy presented with a 1-week history of hypothermia and obtundation.
      His medical history included surgical resection of craniopharyngioma with
      postoperative visual impairment and panhypopituitarism. The patient's rectal
      temperature remained persistently lower than 35 degrees C during the first 3 days
      of hospitalization. His blood pressure was 90/56 mmHg on admission. The
      peripheral blood leukocyte count was 2.7 x 10(10)/L with 18% neutrophils, 19%
      band forms, 44% metamyelocytes, 3% myelocytes, and 16% lymphocytes. The C
      reactive protein concentration was 133.9 mg/L. Two separate blood cultures both
      yielded Pseudomonas putida. The patient was treated with amikacin and ceftazidime
      along with aggressive fluid therapy. Replacement therapy directed at his hormonal
      deficiencies was initiated as soon as his hemodynamic status was stabilized. The
      patient responded well to therapy with a gradual rise in body temperature and
      improvement in general activity. A growth experiment carried out on the P. putida
      isolate showed that the bacteria grew more rapidly at 30 degrees C than at 37
      degrees C. The clinical course of the patient, as well as the results of the
      laboratory study, suggest that hypothermia may predispose human infection with P.
      putida.

PMID- 9585683
TI  - Intraluminal involvement of thyroid cancer in the trachea.
AB  - Invasion of the air passage, especially with intraluminal involvement of well
      differentiated thyroid carcinoma, is rare. Establishing a patent airway before
      surgery is necessary, but difficult and risky. We report a case of thyroid cancer
      with intraluminal invasion of the trachea. A 62-year-old schizophrenic woman
      presented with blood-tinged sputum and dyspnea. She had undergone a thyroid
      lobectomy 8 years previously. Computed tomography and bronchoscopy showed a
      protruding mass in the upper trachea and limited movement of the bilateral vocal
      folds. Emergency tracheostomy was performed to relieve impending apnea. Fine
      needle aspiration of the left protruding thyroid gland showed papillary
      carcinoma. Because the tumor diffusely infiltrated the thyroid gland and
      intermingled with fibrosis due to the previous thyroid operation, and because
      there was limited movement of bilateral vocal folds, the patient underwent total
      laryngectomy, total thyroidectomy, total parathyroidectomy, and tracheal
      resection. Neither radioactive iodine nor external irradiation were given because
      of anticipated poor compliance due to schizophrenia. The postoperative course was
      smooth and thyroid hormone and calcium were supplemented regularly. The patient
      has lived well and without local recurrence for more than 3 years since the
      operation. She can speak with an artificial larynx.

PMID- 9585684
TI  - Effects of an abdominal binder and electrical stimulation on cough in patients
      with spinal cord injury.
AB  - We explored the effect of an abdominal binder, with or without electrical
      stimulation, on peak expiratory flow rate (PEFR) in 12 paraplegics with complete
      thoracic cord (T2-T12) injury (mean age 36.0 +/- 1.5 yr) and 12 quadriplegics
      with complete cervical cord (C4-C8) injury (mean age 36.2 +/- 1.9 yr). The cough
      was assessed by measuring the PEFR during forceful expiration in a sitting
      position. The subjects underwent the following experimental maneuvers in a random
      order with a 10-minute interval between any two maneuvers: 1) voluntary coughing,
      2) voluntary coughing with an abdominal binder, and 3) voluntary coughing with an
      abdominal binder and electrical stimulation. The electrical stimulator (50 Hz
      with 300 microseconds pulse width) was applied to the abdominal wall. Data were
      analyzed using multivariate analysis of variance for repeated measures. The
      abdominal binder did not significantly increase PEFR in either paraplegics or
      quadriplegics; the abdominal binder combined with electrical stimulation
      significantly increased PEFR by 15% in the paraplegics and 18% in the
      quadriplegics. These results indicate that electrical stimulation combined with
      an abdominal binder improves the cough ability in patients with cervical or
      thoracic spinal cord injury.

PMID- 9585685
TI  - Myelination arrest demonstrated using magnetic resonance imaging in a child with
      type I GM1 gangliosidosis.
AB  - An 18-month-old girl was diagnosed as having GM1 gangliosidosis, on the basis of
      the clinical symptoms of muscle stiffness, developmental retardation,
      hepatosplenomegaly, and kyphoscoliosis and a laboratory study that revealed a
      deficiency in the lysosomal degradative enzyme beta-galactosidase. Magnetic
      resonance T1-weighted images showed persistent hyperintensity in the bilateral
      thalami, brainstem, and deep cerebellum at 14 and 18 months of age, indicating
      arrest of the myelination process in these areas, and that the arrest had
      occurred at the newborn stage. There was no myelination in the basal ganglia and
      diffuse leukomalacia developed in the cerebral hemispheres. Only supportive
      treatment was given; the patient died at 2 years of age. Myelination arrest at
      the newborn stage associated with progressive leukomalacia is a possible
      characteristic of GM1 gangliosidosis.

PMID- 9585686
TI  - Lawson Tait and opposition to germ theory: defining science in surgical practice.

PMID- 9585687
TI  - The last past plague: the uses of memory in Renaissance epidemics.

PMID- 9585688
TI  - Karl August Weinhold and his "science" in the era of Mary Shelley's Frankenstein:
      experiments on electricity and the restoration of life.

PMID- 9585689
TI  - When your patient asks: "Doctor, I read there have been serious Pap smear errors.
      Shouldn't I get one of those new computer Pap smears?".

PMID- 9585690
TI  - Laryngeal nerve monitoring during thyroidectomy.
AB  - Electromyographic monitoring of vocal cord function during thyroidectomy is a
      very useful technique. It is non-invasive and provides valuable intraoperative
      data regarding the function of the recurrent laryngeal nerve.

PMID- 9585691
TI  - The Mississippi State Department of Health Central Cancer Registry: purposes and
      potential uses.

PMID- 9585692
TI  - [In vitro activities of faropenem against clarithromycin resistance Helicobacter
      pylori isolates].
AB  - Agar dilution and semi-solid agar dilution were used to determine the MIC of
      faropenem (FRPM) against 24 H. pylori isolates. FRPM was active against
      clarithromycin resistance H. pylori isolates. And, the MICs obtained by both
      methods were in agreement. The results suggest that FRPM was not affected by pH
      and is a clinically useful oral antibiotic for the eradication therapy of H.
      pylori infections.

PMID- 9585693
TI  - [Bactericidal and anti-toxin activities of catechin on enterohemorrhagic
      Escherichia coli].
AB  - We examined the bactericidal activity of catechin, an astringent ingredient of
      tea, on enterohemorrhagic Escherichia coli (EHEC) O157:H7 and the anti-toxin
      activity of catechin on vero toxin (VT), the main pathogenic factor of EHEC
      O157:H7. To examine bactericidal activity, we added 1 X 10(4) CFU/ml bacteria to
      1.25 to 20 W/V% of green tea extract or the PBS solution containing 25 to 400
      micrograms/ml of (-) epigallocatechin gallate (EGCg), which is the main catechin
      ingredient of green tea leaf, and counted the number of live bacteria at various
      intervals. After 3 to 5 hours, no live bacteria were seen in 1.25 to 2.5 (regular
      drinking concentration) % green tea extract. In the high concentrations of 100 to
      400 micrograms/ml EGCg the number of live bacteria decreased with time and after
      24 hours no survivors were seen. In the low concentrations of 25 to 50
      micrograms/ml EGCg, however, no change was observed in the number of live
      bacteria during 5 hours. After 24 hours the bacteria in 50 micrograms/ml were
      killed and the number of bacteria in 25 micrograms/ml decreased to one tenth of
      that at the start. To examine the anti-toxin activity, we mixed equal volumes of
      2 ng/0.1 ml VT2 and 0.5 to 2 mg/0.1 ml catechin in vitro and incubated them at 37
      degrees C for various times. Then we inoculated 0.2 ml of the mixture
      intraperitonealy to BALB/c mice. One mg of catechin inhibited by 100% the lethal
      toxicity of 2 ng of VT2 (LD 100) to mice. The inhibition of lethal toxicity of
      VT2 by catechin depended on the incubation time. The rate of inhibition was 0, 40
      and 100% for 9, 12 and 18-24 hours incubation, respectively. These results
      suggest that catechin has not only bactericidal activity on EHEC O157:H7 but also
      anti-toxin activity on vero toxin.

PMID- 9585694
TI  - [Survival of Vibrio cholerae non-O1 in river sediment during cold season].
AB  - To assess the existence of Vibrio cholerae non-O1 in the environment water system
      during the cold season, the organism was incubated in both river sediment or
      terrestrial soil as particle matter-water (1:1) suspension. The low temperature
      condition was set to 5 degrees and 10 degrees C. At 5 degrees C, V. cholerae non
      O1 did not grow in any medium, sediment and soil. At 10 degrees C, the decrease
      of the number of organisms was delayed in river sediment as compared with peptone
      medium. At 30 degrees C, the organism grew in river sediment and its extract
      solution. In soil, the organism was decreased immediately under low temperature.
      Though the number of organisms was decreased temporarily in soil, its number was
      maintained within 14 days at 30 degrees C. But in the extract solution from soil,
      the organism was decreased immediately under 5 degrees, 10 degrees, 20 degrees,
      30 degrees C. It showed that survival of V. cholerae non-O1 was maintained in
      particle substances contained water. These results suggested that V. cholerae non
      O1 would be able to exist in river sediment during the cold season.

PMID- 9585695
TI  - [Selective screening of enterohemorrhagic Escherichia coli depending on hemolysis
      on Beutin's washed sheep blood agar plates].
AB  - Recently, Beutin et al have studied hemolysin production in a large number of
      serologically diverse verotoxin (VT) producing Escherichia coli (VTEC) strains
      and found a close association between hemolysin production and VT production.
      This study was to examine whether hemolysin production on sheep blood agar can be
      used as an epidemiological marker for microbiological screening of
      enterohemorrhagic Escherichia coli (EHEC). In comparison of hemolysis on washed
      blood agar plates prepared in our laboratory and commercially available blood
      agar, all VT producing strains exhibited a typical hemolytic phenotype on the
      former, on the other hand, VT non-producers were less hemolytic on the former
      than the latter. On the washed blood agar, 11 VT1 producing strains belonging to
      4 different serotypes, 1 strain of VT2 producer, 5 VT1&2 producers belonging to 2
      different serotypes, all the 17 strains of VTEC were positive for hemolysis. The
      85 VT non-producing strains belonging to 18 different serotypes isolated from
      faecal specimens from patients with diarrhea were tested, 10 strains (12%)
      belonging to 4 different serotypes (O6, 18, 26, UT: untypable) produced
      hemolysin. Two-hundred four (10%) of the 2,036 strains isolated from faecal
      specimens from 507 healthy persons exhibited typical hemolysis. As a result of
      identification of these 204 hemolytic strains, 148 strains of E. coli 13 strains
      of Citrobacter and 10 strains of other enterobacteria, and 13 strains of
      Pseudomonas, 12 strains of Aeromonas, 5 strains of Proteus and 3 strains of
      Vibrio were detected. 148 hemolytic strains of E. coli were carried out O
      serotyping with commercially available pathogenic E. coli antisera, 57 strains
      (39%) were classified into 11 different serotypes, but 91 strains were not
      typable. Most frequent serotype was O18 (24 strains), next O6 (18 strains), and
      other 8 different serotypes (O25, 26, 28ac, 29, 55, 146, 152, 159) were less than
      2 strain respectively.

PMID- 9585696
TI  - [Inducibility of tumor necrosis factor alpha to peritoneal macrophages and
      lethality to mice of clinical isolates of Staphylococcus aureus].
AB  - When murine resident peritoneal macrophages were treated in vitro with overnight
      culture supernatants of clinical isolates of S. aureus (21 strains)(S. aureus-CS)
      for 4 hrs at 37 degrees C in a 5% CO2-air humidified incubator, TNF alpha
      induction from the treated cells was observed in 20/21 strains. The amount of TNF
      alpha dispersed from 88.4 to 1726.5 pg/ml but more or less amount of TNF alpha
      did not relate with the presence of TSST-1 and enterotoxin production of S.
      aureus. Recombinant protein A induced TNF alpha production by macrophages dose
      dependently, but the relationship between the amount of protein A in each S.
      aureus CS and that of TNF alpha induced from macrophages treated with them were
      not satisfactory (r = 0.69). When each strain was injected (X10(9) bacterial
      cells) interperitonealy to mice, 13/21 strains indicated lethal activity.
      Relation between TNF alpha inducibility in vitro and lethal activity, however,
      was not found (r = 0.4). These results suggest that TNF alpha inducibility is the
      basic biological activity of S. aureus, although there is a difference in the
      induction amount and in component(s) to induce TNF alpha on each strain, and then
      because the strain is strong in TNF alpha inducibility, it does not necessarily
      follow that pathogenicity is strong.

PMID- 9585697
TI  - [Mycobacterial lung infection in 8 patients with AIDS: clinical and radiological
      features].
AB  - The prevalence of mycobacterial infection in AIDS patients has increased in
      Japan. This report describes details of the clinical and radiological features of
      eight AIDS patients with mycobacterial disease (6 with M. tuberculosis infection
      and 2 with M. kansasii infection) in our hospital during the period from October
      1995 through February 1997. Six of the 8 were men, and two were women. The mean
      age was 36.5 years. Six were Japanese, one was from Myanmar, and one was
      Malaysian. The median CD4 positive T lymphocyte counts (CD4 count) at the time of
      diagnosis of the M. tuberculosis was 75.5 (range 14-569/microliter, and the M.
      kansasii was 21.5 (range 19-24)/microliter. Clinical findings and symptoms of all
      patients were non-specific, but almost all patients had a cough and fever. In the
      radiographic findings, the patients of the M. tuberculosis group presented
      multiple hilar and mediastinal lymphadenopathy, miliary shadow, and obstructive
      pneumonia. Both M. kansasii patients showed a multiple infiltration shadow. There
      were no drug resistant strains in M. tuberculosis except on isolate with moderate
      resistant. to Streptomycin. These observations suggest that AIDS-associated
      mycobacterial disease shows atypical clinical and radiological features in some
      cases, especially in advanced stages of AIDS. Therefore, we need to recognize the
      characteristics of the clinical and radiological features of the patients with
      mycobacterial diseases and AIDS.

PMID- 9585698
TI  - [Investigation of the influence of hemodialysis membranes and factors associated
      with hemodialysis on serum (1-->3)-beta-D-glucan].
AB  - The measurement of serum (1-->3)-beta-D-glucan (beta-glucan) is commonly used in
      the clinical stage. Although it has been considered very useful in the early
      diagnosis of deep mycosis, it is influenced by several factors, one of which is
      hemodialysis. Therefore, we decided to investigate clinically the influence of
      hemodialysis membranes on serum beta-glucan. Plasma samples were collected from
      26 patients receiving hemodialysis in Kawasaki Medical School Hospital. The kinds
      of hemodialysis membranes examined were four synthetic polymers and three natural
      polymers. We also measured beta-glucan in five washing liquids used in the
      hemodialysis circuit, five dialyzates, two sodium heparin and two filling liquids
      for wet type dialyzers to investigate the influence of other factors associated
      with hemodialysis on serum beta-glucan. Elevations of beta-glucan were observed
      in some cases treated by hemodialysis apparatus using a saponified cellulose
      acetate membrane. But, in all cases treated by hemodialysis using a cellulose
      triacetate membrane, slight elevations of beta-glucan were observed. No
      significant increases in beta-glucan after hemodialysis were observed in the
      cases treated by hemodialysis using a synthetic polymer membrane. Elevations of
      beta-glucan is sodium heparin and in one of the filling liquids for the wet type
      dialyzer were observed. We, therefore, concluded that there are some other
      factors having an effect on serum beta-glucan besides the hemodialysis membrane
      in the patients treated by hemodialysis.

PMID- 9585699
TI  - [Evaluation of a synthetic peptide based species specific EIA kit for detection
      of antibodies to Chlamydia trachomatis with clinical specimens].
AB  - We have evaluated a new kit, PEPTIDE Chlamydia (Meiji Milk Products Co., Ltd,
      Tokyo), for detecting species specific antibodies to Chlamydia trachomatis with
      synthetic peptide as an antigen. Serum samples from women with C. trachomatis
      cervicitis (n = 45), healthy pregnant women (n = 100), and children suffering
      from C. pneumoniae lower respiratory tract infection (n = 9) were used. We have
      measured the serum IgG or IgA antibodies to C. trachomatis of those sera with
      PEPTIDE, Sero IPALIZA Chlamydia (Savyon Diagnostics, Israel), and HITAZYME
      Chlamydia (Hitachi Chemical Co., Ltd, Hitachi). Serum samples with discrepant
      results were further analyzed by a microimmunofluorescence test and
      immunoblotting (western blotting). IgG and IgA serum positive rate to C.
      trachomatis of sera from women with C. trachomatis cervicitis were similar in
      three kits, that is, 91% and 80% in PEPTIDE, 89% and 82% in Sero IPALIZA, and 84%
      and 76% in HITAZYME, respectively. IgG and IgA serum positive rate to C.
      trachomatis of sera from healthy pregnant women were 18% and 9% in PEPTIDE, 12%
      and 15% in Sero IPALIZA, and 15% and 13% in HITAZYME, respectively. Serum
      antibodies to C. trachomatis in serum samples from children with C. pneumoniae
      infection were all negative in PEPTIDE, but falsely positive in several cases in
      Sero IPALIZA or HITAZYME. In sera with discrepant results, PEPTIDE gave more
      identical results with a micro-IF test and immunoblotting analysis than Sero
      IPALIZA or HITAZYME. These results indicate that PEPTIDE is an useful kit to
      detect more species specific antibodies to Chlamydia trachomatis than former
      kits.

PMID- 9585700
TI  - [Report of surveillance on streptococcal toxic shock syndrome in Japan and
      presentation of the criteria].
AB  - A survey was made on the situation of Group A Streptococcal toxic shock syndrome
      (STSS) based on questionnaires. The survey was divided into two parts. The first
      survey was done by sending out an outline of the STSS inquiring if any STSS cases
      were observed by mail to university hospitals, residence training hospital and
      other major hospitals totaling 2512 institutes. The second survey was
      subsequently done to the institutes that had STSS cases asking for the clinical
      course, data and sampling of the bacteria. The diagnosis of STSS was confirmed
      based on the diagnostic criteria induced by the working group of the United
      States. We have found 97 cases of STSS which 48.5% had fatal outcomes. There was
      no significant sex difference in the onset or the mortality rate. It occurred
      more in the older population, and occurred through out Japan but was not found to
      be epidemic. The first case was backed in 1978 and it began to increase since
      1993, reaching its peak in 1994 and now decreasing in number. Most of the
      isolated Group A streptococcus were of type M1 and M3. We have modified the
      United States diagnostic criteria creating a new Japanese criteria, which
      includes the symptoms of the central nervous system in the term MOF. The aim for
      the Japanese criteria is to search for the etiology of the disease. The Japanese
      criteria requires that the disease progresses rapidly and that the patient be
      free from any conditions that might suppress the immunal system.

PMID- 9585701
TI  - [Real time observation of binding of measles virus to Vero cells and
      neutralization of measles virus by human immunoglobulin using optical biosensor-
      a new real time diagnosis system for viral infections].
AB  - An optical biosensor to monitor molecular intractions was developed. This system
      made possible to observe reactions with a few minutes. We tried to apply this
      system for rapid diagnosis of viral infections. Measles virus propagated in our
      laboratory and crude rabbit anti-measles antiserum were used. A commercially
      available human immunoglobulin was used as a representative of patient sera. A
      crude rabbit anti-measles antiserum was fixed on the reaction surface of
      aminosilane coated cuvette, and specific binding of measles virus to this
      antibody was monitored. Specific purified IgG antibody was known to give as high
      sensitivity as the conventional culture method. But the sensitivity by crude
      antibody was found to be 1/10 in the sensitivity. This might be caused by the
      masked effects on specific antibody to the contaminated high amounts of non
      specific proteins. None purified polyclonal antisera for most of the viruses are
      commercially available, and 10-20 times highly concentrated antibody solutions
      could be used for this titrations. Estimated anti-measles antibody titer of the
      commercial available human immunoglobulin by biosensor system was found to be the
      same as that by the conventional culture method. It was suggested that 1 X 10(3)
      virus particles/ml in the test solutions could be detectable and titerable by
      using commercially available specific anti-viral antibody in real time, and the
      viral infections could be diagnosed within an hour.

PMID- 9585702
TI  - [Clinical analysis on 127 cases of fungemia in Fukuoka University Hospital
      between 1984 and 1994].
AB  - A clinical analysis on 127 cases out of 140 cases presenting with fungemia at
      Fukuoka University Hospital between 1984 and 1994 was done. The number of the
      positive blood cultures during the same period was 1188 and the rate of fungemia
      was 11.8%. The rates generally increased in recent years, 9.0% (1984-1986), 10.2%
      (1987-1989) and 13.6% (1990-1994), but decreased after 1992. C. albicans has
      shown a tendency to decrease while C. parapsilosis and C. glabrata have increased
      in recent years thus suggesting the effect of the prevalence of intravenous
      hyperalimentation (IVH) and azole antifungal agents. Only 3.9% of the fungemia
      were preceded by bacteremia. In addition to the known risk factors for fungemia
      such as IVH (89.0%) and the antibacterial agents, H2-receptor antagonists were
      used in 58.3% of the cases. 14 cases of the fungemia were observed during the
      prophylactic use of antifungal drugs. Therefore, fungemia should always be kept
      in mind regarding the differential diagnosis for bacteremia when an indwelling
      venous catheter is used. The prompt extubation of the catheter in addition to the
      adjustment of the dosage of antifungal drugs in response to the status of the
      host defense system are thus considered to be important in the treatment of
      fungemia.

PMID- 9585703
TI  - [Early manifestation of septic shock and disseminated intravascular coagulation
      complicated by acute myocardial infarction in a patient suspected of having
      Legionnaires' disease].
AB  - Legionellosis is an important cause of severe pneumonia in the community.
      Inadequate therapy will lead to respiratory distress syndrome, disseminated
      intravascular coagulation (DIC) and finally fatal multiple organ failure. We
      encountered a rare case in which early manifestation included septic shock and
      DIC complicated by acute myocardial infarction (AMI) suspected to be derived from
      Legionnaires' disease. A 54-year-old healthy female complained of lumbago, high
      fever and dry cough 10 days after visiting a hot spring spa. She was emmergently
      admitted due to shock. Physical examination demonstrated hypotension, high fever,
      course creakle in the right lower lung. Hepatosplenomegaly, lymphadenopathy and
      eruption were not found. WBC count was 34600/microliters with nuclear shift. CRP
      elevated. FDP, D dimer and TAT also elevated CPK elevated with dominance of the
      MB isozyme. Chest roentogenography revealed congestive heart failure, pleural
      effusion and obscure pneumonic shadow and EKG showed ST segment elevation in
      leads I, II, III, aVF, V4, V5, and V6. The patient was diagnosed as having septic
      shock, DIC and AMI. She was treated with gabexate mesilate, high dose methyl
      prednisolone and dopamine hydrochloride as well as piperacillin, meropenem,
      isepamycin and fluconzaole. Despite intensive care, the blood pressure fell again
      and pneumonia had progressed on the 8th hospital day. These antibiotics appeared
      to be ineffective. Erythromycin was then administered and a dramatic effect. was
      obtained as the patient recovered. Serum titer of Legionella pneumophila
      (serogroup 1) rose to 128-fold 2 weeks after the onset. Other serum titers such
      as Chlamydia psittaci, Rickettsia, Mycoplasma were all negative. Cultures
      obtained from the sputum, throat swab, urine and blood did not yield any
      microorganisms. Although the diagnosis could not be confirmed because the titer
      did not elevate over 256-fold of 4-fold within 2 weeks after the onset,
      Legionella infection was highly suspected from the clinical features. This is a
      rare case in which septic shock and DIC with AMI preceded pulmonary symptoms in a
      non-immunocompromised patient.

PMID- 9585704
TI  - Good old science.

PMID- 9585705
TI  - Images in neuroscience. Brain development, II. Establishing synaptic connections.

PMID- 9585706
TI  - For better or worse: interpersonal relationships and individual outcome.
AB  - At a time of strong biological emphasis in psychiatry, it is important to
      emphasize that relationships with important others may play a crucial role in
      individual outcome. Psychoanalytic theories in the form of object relations, self
      psychology, and relational psychoanalysis reflect this emphasis, and at a broader
      level, the interpersonal school of psychiatry focuses selectively on the role of
      relationships in health and illness. Ten central premises of the interpersonal
      school are presented, followed by brief, selective reviews of three bodies of
      empirical data: studies of well-functioning marriages and families, the role of
      adult relationships in undoing the adult consequences of destructive childhood
      experiences, and the relationship of marital variables to the onset and course of
      depressive disorders. Clinical experience and research findings suggest that
      clinicians treating couples and families may be helpful by using techniques
      designed to both increase the intensity of affective bonds and repair the
      inevitable disruptions of those bonds. It is also noted that recent
      psychophysiologic studies suggest that derivatives of intense affective bonds and
      their disruptions, in the form of confiding and conflict, may influence both
      vascular reactivity and cellular immune competence. These studies suggest that
      "for better or worse" may have physiologic as well as psychological implications.

PMID- 9585707
TI  - Anticipation of age at onset in panic disorder.
AB  - OBJECTIVE: Anticipation (i.e., the decrease in age at onset or the increase in
      severity of a disorder in successive generations) has recently been reappraised
      as a key to understanding the genetics of some familial illnesses. The purpose of
      this study was to search for possible anticipation in panic disorder. METHOD:
      Thirty-eight unilineal, multigenerational families with multiple directly
      interviewed members who had panic disorder were compared across two successive
      generations for 1) age at the first panic attack, 2) age at the onset of panic
      disorder, and 3) the highest degree of agoraphobia ever experienced, as a
      tentative index of severity of illness. Intergenerational pairwise comparisons
      were implemented according to four different sampling schemes: random pairs,
      random transmitting pairs, all possible pairs, and all possible transmitting
      pairs. RESULTS: Life table analyses showed a significant decrease in the time
      before the first episode of panic and onset of panic disorder from the older to
      the younger generation. Evidence for anticipation was found for both indexes of
      onset in all four sampling schemes. No evidence of a generational effect on the
      index of severity of agoraphobia was found. Corrections for possible biases
      suggested that these results are not likely to be simple artifacts. CONCLUSIONS:
      Anticipation is supported in this specific set of families and, if it is
      confirmed by other studies, a role for trinucleotide repeat sequences may be
      considered to account for the familial aggregation of panic disorder.

PMID- 9585708
TI  - Is the course of panic disorder the same in women and men?
AB  - OBJECTIVE: Panic disorder with or without agoraphobia has a chronic relapsing
      course. Factors associated with poor outcome include early onset of illness and
      phobic avoidance. Several, but not all, authors have found a worse clinical
      course for women. Using observational, longitudinal data from the Harvard/Brown
      Anxiety Disorders Research Program, the authors analyzed remission and symptom
      recurrence rates in panic patients with respect to sex. METHOD: Male and female
      patients (N = 412) in an episode of panic with or without agoraphobia were
      assessed by structured interview and prospectively followed for up to 5 years.
      Data on remission, symptom recurrence, and comorbid psychiatric conditions for
      each sex were compared. RESULTS: There were no significant differences between
      men and women in panic symptoms or level of severity at baseline. Women were more
      likely to have panic with agoraphobia (85% versus 75%), while men were more
      likely to have uncomplicated panic (25% versus 15%). The rates of remission for
      panic with or without agoraphobia at 5 years were equivalent in men and women
      (39%). Of the subjects who achieved remission, 25% of the women and 15% of the
      men reexperienced symptoms by 6 months. Recurrence of panic symptoms continued to
      be higher in women (82%) than men (51%) during the follow-up period and was not
      influenced by concurrent agoraphobia. CONCLUSIONS: This study extends previous
      findings by showing that not only are women more likely to have panic with
      concurrent agoraphobia, but they are more likely than men to suffer a recurrence
      of panic symptoms after remission of panic.

PMID- 9585709
TI  - Comparison of aerobic exercise, clomipramine, and placebo in the treatment of
      panic disorder.
AB  - OBJECTIVE: The purpose of this study was to compare the therapeutic effect of
      exercise for patients with panic disorder to a drug treatment of proven efficacy
      and to placebo. METHOD: Forty-six outpatients suffering from moderate to severe
      panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly
      assigned to a 10-week treatment protocol of regular aerobic exercise (running),
      clomipramine (112.5 mg/day), or placebo pills. RESULTS: The dropout rate was 31%
      for the exercise group, 27% for the placebo group, and 0% for the clomipramine
      group. In comparison with placebo, both exercise and clomipramine led to a
      significant decrease in symptoms according to all main efficacy measures
      (analysis of variance, last-observation-carried-forward method and completer
      analysis). A direct comparison of exercise and clomipramine revealed that the
      drug treatment improved anxiety symptoms significantly earlier and more
      effectively. Depressive symptoms were also significantly improved by exercise and
      clomipramine treatment. CONCLUSIONS: These results suggest that regular aerobic
      exercise alone, in comparison with placebo, is associated with significant
      clinical improvement in patients suffering from panic disorder, but that it is
      less effective than treatment with clomipramine.

PMID- 9585710
TI  - Effect of flumazenil in lactate-sensitive patients with panic disorder.
AB  - OBJECTIVE: Flumazenil is a benzodiazepine receptor antagonist that has been
      reported to provoke panic attacks in patients with panic disorder. This study was
      undertaken to compare the effects of flumazenil and sodium lactate, the most
      widely studied panic provocation agent. METHOD: Ten patients with panic disorder
      were given infusions of saline, sodium lactate, and flumazenil in randomized
      order. Panic attacks, psychopathological changes, heart rate, and cortisol and
      ACTH secretion were recorded. RESULTS: Eight of the 10 patients experienced a
      panic attack after sodium lactate, but none did after flumazenil or saline.
      Cortisol and ACTH secretion were not enhanced by any of the treatments. Sodium
      lactate increased heart rate, whereas flumazenil had the opposite effect.
      CONCLUSIONS: These findings do not lend support to the view that the
      benzodiazepine receptors of lactate-susceptible patients with panic disorder are
      hypersensitive and that flumazenil can therefore act as an inverse agonist.

PMID- 9585711
TI  - Social phobia subtypes in the National Comorbidity Survey.
AB  - OBJECTIVE: This article presents epidemiologic data on the distinction between
      social phobia characterized by pure speaking fears and that characterized by
      other social fears. METHOD: The data come from the National Comorbidity Survey (N
      = 8,098). Social phobia was assessed with a revised version of the Composite
      International Diagnostic Interview. RESULTS: Latent class analysis showed that
      the brief set of social fears assessed in the survey can be disaggregated into a
      class characterized largely by speaking fears and a second class characterized by
      a broader range of social fears. One-third of the people with lifetime social
      phobia exclusively reported speaking fears, while the other two-thirds also had
      at least one of the other social fears assessed. The vast majority of the latter
      had multiple social fears including, in most cases, both performance and
      interactional fears. The two subtypes were similar in age at onset distribution,
      family history, and certain sociodemographic correlates. However, the social
      phobia characterized by pure speaking fears was less persistent, less impairing,
      and less highly comorbid with other DSM-III-R disorders than was social phobia
      characterized by other social fears. CONCLUSIONS: Further general population
      research assessing more performance and interaction fears is needed to determine
      whether social phobia subtypes can be refined and whether the subtypes are better
      conceptualized as distinct disorders. In the meantime, people who have social
      phobia with multiple fears, some of which are nonspeaking fears, appear to have
      the most impairment and should be the main focus of prevention and intervention
      efforts.

PMID- 9585712
TI  - Acute stress disorder as a predictor of posttraumatic stress symptoms.
AB  - OBJECTIVE: Using the DSM-IV diagnostic criteria for acute stress disorder, the
      authors examined whether the acute psychological effects of being a bystander to
      violence involving mass shootings in an office building predicted later
      posttraumatic stress symptoms. METHOD: The participants in this study were 36
      employees working in an office building where a gunman shot 14 persons (eight
      fatally). The acute stress symptoms were assessed within 8 days of the event, and
      posttraumatic stress symptoms of 32 employees were assessed 7 to 10 months later.
      RESULTS: According to the Stanford Acute Stress Reaction Questionnaire, 12 (33%)
      of the employees met criteria for the diagnosis of acute stress disorder. Acute
      stress symptoms were found to be an excellent predictor of the subjects'
      posttraumatic stress symptoms 7-10 months after the traumatic event. CONCLUSIONS:
      These results suggest not only that being a bystander to violence is highly
      stressful in the short run, but that acute stress reactions to such an event
      further predict later posttraumatic stress symptoms.

PMID- 9585713
TI  - Relationship between acute stress disorder and posttraumatic stress disorder
      following mild traumatic brain injury.
AB  - OBJECTIVE: The aim of this study was to index the frequency of occurrence of
      acute stress disorder following mild traumatic brain injury and to determine its
      utility in predicting posttraumatic stress disorder (PTSD). METHOD: Consecutive
      adult patients who sustained a mild traumatic brain injury following a motor
      vehicle accident (N = 79) were assessed for acute stress disorder within 1 month
      of their trauma with the Acute Stress Disorder Inventory, a structured clinical
      interview based on DSM-IV criteria. Patients were followed up 6 months after the
      trauma (N = 63) and were administered the PTSD module of the Composite
      International Diagnostic Interview. RESULTS: Acute stress disorder was diagnosed
      in 14% of patients, and at follow-up 24% satisfied criteria for PTSD. Six months
      after the trauma PTSD was diagnosed in 82% of patients who had been diagnosed
      with acute stress disorder and in 11% of those who had not been diagnosed with
      acute stress disorder. CONCLUSIONS: These findings point to the frequency of PTSD
      following mild traumatic brain injury. While the criteria for acute stress
      disorder are useful in identifying those individuals who are at risk of
      developing chronic PTSD, the findings suggest that current criteria require
      modification in order to optimally predict PTSD following mild traumatic brain
      injury.

PMID- 9585714
TI  - Prospective study of posttraumatic stress disorder and depression following
      trauma.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate the onset,
      overlap, and course of posttraumatic stress disorder (PTSD) and major depression
      following traumatic events. METHOD: The occurrence of PTSD and major depression
      and the intensity of related symptoms were assessed in 211 trauma survivors
      recruited from a general hospital's emergency room. Psychometrics and structured
      clinical interview (the Structured Clinical Interview for DSM-III-R and the
      Clinician-Administered PTSD Scale) were administered 1 week, 1 month, and 4
      months after the traumatic event. Heart rate was assessed upon arrival at the
      emergency room for subjects with physical injury. Twenty-three subjects with PTSD
      and 35 matched comparison subjects were followed for 1 year. RESULTS: Major
      depression and PTSD occurred early on after trauma; patients with these diagnoses
      had similar recovery rates: 63 survivors (29.9%) met criteria for PTSD at 1
      month, and 37 (17.5%) had PTSD at 4 months. Forty subjects (19.0%) met criteria
      for major depression at 1 month, and 30 (14.2%) had major depression at 4 months.
      Comorbid depression occurred in 44.5% of PTSD patients at 1 month and in 43.2% at
      4 months. Comorbidity was associated with greater symptom severity and lower
      levels of functioning. Survivors with PTSD had higher heart rate levels at the
      emergency room and reported more intrusive symptoms, exaggerated startle, and
      peritraumatic dissociation than those with major depression. Prior depression was
      associated with a higher prevalence of major depression and with more reported
      symptoms. CONCLUSIONS: Major depression and PTSD are independent sequelae of
      traumatic events, have similar prognoses, and interact to increase distress and
      dysfunction. Both should be targeted by early treatment interventions and by
      neurobiological research.

PMID- 9585715
TI  - Lithium maintenance treatment of depression and mania in bipolar I and bipolar II
      disorders.
AB  - OBJECTIVE: Effects of long-term lithium treatment for depressive and manic phases
      of type I and type II bipolar disorders were compared. METHOD: Clinical research
      records of 317 patients with DSM-IV-defined bipolar disorder (188 with type I and
      129 with type II) were analyzed for frequency and duration of affective episodes
      and hospitalizations before (mean = 8.38 years) versus during (mean = 6.35 years)
      lithium maintenance treatment. Treatment effects were also assessed by survival
      analysis of interepisode intervals and by multivariate regression testing for
      factors associated with response to treatment. RESULTS: Bipolar I and bipolar II
      patients were ill before treatment a similar percentage of time, but the subtype
      distinction was supported descriptively. Lithium had superior benefits in type II
      patients, with significantly greater reduction of episodes per year and of the
      percentage of time ill. Reduction of depressive morbidity was similarly strong in
      both diagnostic types. During treatment, bipolar II patients had 5.9-fold longer
      interepisode intervals and were twice as likely as type I patients to have no new
      episodes. Starting lithium maintenance earlier predicted greater improvement.
      CONCLUSIONS: Lithium maintenance yielded striking long-term reductions of
      depressive as well as manic morbidity in both bipolar disorder subtypes, with
      greater overall benefits in type II patients and with earlier treatment.

PMID- 9585716
TI  - 12-month outcome of patients with bipolar disorder following hospitalization for
      a manic or mixed episode.
AB  - OBJECTIVE: The authors studied the 12-month course of illness following
      hospitalization for a manic or mixed episode of bipolar disorder to identify
      potential outcome predictors. METHOD: They recruited 134 patients with DSM-III-R
      bipolar disorder who were consecutively admitted for the treatment of a manic or
      mixed episode. Diagnostic, symptomatic, and functional evaluations were obtained
      at the index hospitalization. Patients were reevaluated at 2, 6, and 12 months
      after discharge to assess syndromic, symptomatic, and functional outcome. Factors
      associated with outcome were identified by using multivariate analyses. RESULTS:
      During the 12-month follow-up period, there were no significant differences in
      outcome between patients with manic compared with mixed bipolar disorder.
      Although syndromic recovery occurred in 48% of the overall group, symptomatic
      recovery occurred in only 26% and functional recovery in only 24%. Predictors of
      syndromic recovery included shorter duration of illness and full treatment
      compliance. Medication treatment compliance was inversely associated with the
      presence of comorbid substance use disorders. Symptomatic and functional recovery
      occurred more rapidly and in a greater percentage of patients from higher social
      classes. CONCLUSIONS: A minority of patients with bipolar disorder achieved a
      favorable outcome in the year following hospitalization for a manic or mixed
      episode. Shorter duration of illness, higher social class, and treatment
      compliance were associated with higher rates of recovery and more rapid recovery.

PMID- 9585717
TI  - 30-month stability of personality disorder diagnoses in depressed outpatients.
AB  - OBJECTIVE: This study examined the 30-month stability of axis II conditions.
      METHOD: One hundred eight depressed outpatients received comprehensive,
      semistructured personality disorder assessments at baseline and at follow-up.
      RESULTS: The diagnostic stability of personality disorders ranged from low to
      moderate at the categorical level and was generally moderate at the dimensional
      level. Most disorders exhibited good discriminant validity, in that the
      association between a disorder at baseline and at follow-up was greater than the
      associations between that disorder at baseline and the other 11 axis 11 disorders
      at follow-up. Two variables, sex and lifetime history of substance abuse or
      dependence, were significantly related to change in level of personality disorder
      features over time. CONCLUSIONS: Personality disorders have low to moderate
      stability over a 30-month period in depressed outpatients.

PMID- 9585718
TI  - Cardiovascular effects of fluoxetine in depressed patients with heart disease.
AB  - OBJECTIVE: The purpose of this study was to determine the cardiovascular effects
      of fluoxetine in depressed patients with cardiac disease. METHOD: Twenty-seven
      depressed patients (26% of whom were female and whose average age was 73 years)
      who had congestive heart failure, conduction disease, and/or ventricular
      arrhythmia were studied in an open medication trial of fluoxetine, up to 60
      mg/day, for 7 weeks. The main outcome measures were heart rate and rhythm
      measured by 24-hour ECG recordings, ejection fraction determined by radionuclide
      angiography, cardiac conduction intervals, and blood pressure. Baseline values
      were compared with those at weeks 2 and 7 of fluoxetine treatment. In 60
      comparable patients, values of these same cardiovascular measures at baseline and
      after 3 weeks of treatment with a tricyclic antidepressant, nortriptyline, were
      also examined. RESULTS: Fluoxetine induced a statistically significant 6%
      decrease in heart rate, a 2% increase in supine systolic pressure, and a 7%
      increase in ejection fraction. There was no effect on cardiac conduction,
      ventricular arrhythmia, or orthostatic blood pressure. Overall, 4% of the
      fluoxetine patients had an adverse cardiovascular effect. In contrast,
      nortriptyline treatment caused a significant increase in heart rate and
      orthostatic hypotension, and 20% of the nortriptyline-treated patients had an
      adverse cardiovascular effect. CONCLUSIONS: In depressed patients with heart
      disease, fluoxetine treatment was not associated with the cardiovascular effects
      documented for the tricyclic antidepressants or with significant adverse cardiac
      events. However, limited conclusions about fluoxetine's cardiovascular effects
      and safety can be drawn from this study of only 27 patients monitored for 7
      weeks.

PMID- 9585719
TI  - Dynamics of ECT normalization of low G protein function and immunoreactivity in
      mononuclear leukocytes of patients with major depression.
AB  - OBJECTIVE: Heterotrimeric G proteins were previously implicated in the
      biochemical mechanisms underlying the pathophysiology and treatment of mood
      disorders. Low function and immunoreactivity of G proteins were observed in
      patients with major depression. In the present study the authors evaluated the
      effects of ECT on the low measures of G proteins in patients with major
      depression. METHOD: Repeated G protein measurements in mononuclear leukocytes of
      10 patients with major depression were made. Each patient was examined while
      untreated and after successive sessions of ECT; 14 normal subjects were also
      studied. G protein function was evaluated through beta-adrenergic- and muscarinic
      agonist-enhanced guanine nucleotide binding capacity, substantiated by
      quantitative measures of G proteins through immunoblot analyses using polyclonal
      antibodies against Gs alpha, Gi alpha, and G beta proteins. RESULTS: Mononuclear
      leukocytes of patients with depression showed immunoreactive levels of Gs alpha
      and Gi alpha that were significantly lower than those of normal subjects; the
      depressed patients also had markedly hypofunctional Gs and Gi. The low levels of
      G protein function and immunoreactivity were alleviated by ECT. Repeated
      measurements in the same patients after successive ECT sessions showed that the
      normalization of G protein measures preceded, and thus predicted, clinical
      improvement. The function and quantity of Gs and Gi proteins in patients given
      ECT were significantly correlated. CONCLUSIONS: These findings support the
      implication of G proteins in the pathophysiology and treatment of mood disorders.
      G protein measurements in patients with depression may potentially serve not only
      as a biochemical marker for affective state but also for biochemical prediction
      and evaluation of responses to ECT.

PMID- 9585720
TI  - IQ decline during childhood and adult psychotic symptoms in a community sample: a
      19-year longitudinal study.
AB  - OBJECTIVE: The goal of this study was to examine cognitive antecedents of
      psychosis by determining whether variability in IQ during childhood was
      predictive of psychotic symptoms in adulthood. METHOD: Deviant responder analyses
      were used to examine prospectively the relationship of IQ at ages 4 and 7 to
      psychotic symptoms at age 23 in 547 offspring from a community sample (National
      Collaborative Perinatal Project) that was unselected for psychiatric illness. The
      authors compared three hypotheses: that 1) low IQ, 2) large IQ fluctuations
      regardless of direction, or 3) large IQ declines would predict the presence of
      adult psychotic symptoms. RESULTS: The 10% of individuals with substantially
      larger than expected IQ declines from age 4 to 7 had a rate of psychotic, but not
      other psychiatric, symptoms at age 23 that was nearly seven times as high as the
      rate for other persons. Parental socioeconomic status and IQ at age 7 also
      predicted adult psychotic symptoms. However, when IQ at age 7, IQ decline between
      ages 4 and 7, and socioeconomic status were all included in a logistic regression
      analysis, only IQ decline remained significant. CONCLUSIONS: There is an
      increased likelihood of developing psychotic symptoms in adulthood for a subgroup
      of individuals with substantially greater than expected IQ declines during
      childhood. IQ decline is specific for psychotic symptoms, but follow-up
      assessment when the study participants are further into the age of risk will be
      necessary to determine specificity for schizophrenia. The authors discuss the
      implications of this early cognitive downturn for a neurodevelopmental view of
      schizophrenia.

PMID- 9585721
TI  - Progressive reduction of temporal lobe structures in childhood-onset
      schizophrenia.
AB  - OBJECTIVE: A previous cross-sectional study of brain morphology in childhood
      onset schizophrenia indicated sparing of the temporal lobes from processes
      reducing total cerebral volume in this population. In the present study, subjects
      with childhood-onset schizophrenia and healthy subjects were rescanned at 2-year
      follow-up to determine whether this pattern of temporal lobe sparing persists
      with ongoing illness. METHOD: Anatomic brain magnetic resonance imaging scans
      were acquired for 10 adolescent patients with average onset of schizophrenia at
      10.4 years (SD = 1.7) and 17 healthy adolescents. Scans were obtained on initial
      admission and at 2-year follow-up by using identical equipment and measurement
      methodology. RESULTS: Schizophrenic subjects showed significantly greater
      decreases than healthy subjects in right temporal lobe, bilateral superior
      temporal gyrus and posterior superior temporal gyrus, right anterior superior
      temporal gyrus, and left hippocampal volumes during the follow-up interval.
      Decline in right posterior superior temporal gyrus was associated with high total
      scores on the Scale for the Assessment of Positive Symptoms at baseline and at
      follow-up. CONCLUSIONS: Progressive reduction of temporal lobe structures occurs
      with ongoing illness in childhood-onset schizophrenia.

PMID- 9585722
TI  - Integrating pharmacotherapy and psychotherapy in the treatment of a bipolar
      patient.

PMID- 9585724
TI  - Serum sertraline and N-desmethylsertraline levels in breast-feeding mother-infant
      pairs.
AB  - OBJECTIVE: The authors' goal was to study the serum sertraline levels of breast
      feeding mothers and their infants. METHOD: They obtained serum levels of
      sertraline and N-desmethylsertraline in nine mother-infant pairs. RESULTS:
      Sertraline levels were very low (less than 2 ng/ml) in seven of the nine infants
      and low (3 ng/ml) in one. N-Desmethylsertraline levels were also low (6 ng/ml or
      less) in seven of the nine infants. One infant had a high level of N
      desmethylsertraline, and one infant had unusual serum sertraline and N
      desmethylsertraline values (half of its mother's levels). All infants were
      thriving. CONCLUSIONS: Most breast-feeding infants whose mothers were taking
      sertraline had very low serum levels of both sertraline and N
      desmethylsertraline, consistent with published reports. The authors discuss in
      detail the one infant with unusually high levels.

PMID- 9585725
TI  - Effectiveness and tolerability of tomoxetine in adults with attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: The authors assessed the experimental noradrenergic compound
      tomoxetine as an alternative treatment for adult attention deficit hyperactivity
      disorder (ADHD). METHOD: They conducted a double-blind, placebo-controlled,
      crossover study of tomoxetine in 22 adults with well-characterized ADHD. RESULTS:
      Treatment with tomoxetine at an average oral dose of 76 mg/day was well
      tolerated. Drug-specific improvement in ADHD symptom was highly significant
      overall and sufficiently robust to be detectable in a parallel-groups comparison
      restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed
      improvement after receiving tomoxetine, compared with only two of 21 patients who
      improved after receiving placebo. Significant tomoxetine-associated improvement
      was noted on neuropsychological measures of inhibitory capacity from Stroop
      tests. CONCLUSIONS: This preliminary study showed that tomoxetine was effective
      in treating adult ADHD and was well tolerated. These promising results provide
      support for further studies of tomoxetine over an extended period of treatment.

PMID- 9585726
TI  - Clinical characteristics of attention deficit hyperactivity disorder in African
      American children.
AB  - OBJECTIVE: The authors' goal was to explore the nature of attention deficit
      hyperactivity disorder (ADHD) in African American children, which has received
      scant attention by psychiatric researchers. METHOD: Subjects were 19 African
      American children with DSM-III-R ADHD and 24 African American children without
      ADHD. Ethnically sensitive methods were used to evaluate the children
      comprehensively. The findings were compared with those from an earlier study of
      Caucasian children with ADHD. RESULTS: African American children with ADHD had
      higher levels of psychiatric disorders other than ADHD than did African American
      children who did not have ADHD. CONCLUSIONS: Among African American children,
      ADHD may be characterized by a narrower pattern of psychiatric comorbidity and
      dysfunction than has been observed in Caucasians. Given the small number of
      subjects studied, these findings are preliminary and must be replicated to
      confirm their validity.

PMID- 9585727
TI  - Association of elevated alpha 1-antichymotrypsin with cognitive impairment in a
      prospective study of the very old.
AB  - OBJECTIVE: The authors investigated the relationships between concentrations of
      two acute-phase proteins, alpha 1-antichymotrypsin (ACT) and alpha 2
      macroglobulin (MAC), and cognitive impairment in the very old. METHOD:
      Concentrations of ACT and MAC were determined in a prospective study using sera
      from medically stable elderly nursing home residents. Cognitive impairment was
      assessed with the Mini-Mental State. RESULTS: Concentrations of ACT were
      associated with greater cognitive impairment, as reflected by lower Mini-Mental
      State scores. This relationship did not exist for MAC. CONCLUSIONS: These data
      extend previous reports that patients with Alzheimer's disease have greater
      concentrations of ACT in their blood by demonstrating in a diagnostically diverse
      nursing home population a relationship between serum ACT and mental status.
      Elevated serum ACT in patients with compromised mental status may reflect a
      cerebral acute-phase response.

PMID- 9585728
TI  - Anorexia nervosa in one monozygotic twin.

PMID- 9585729
TI  - Dissociative symptoms in children.

PMID- 9585730
TI  - Psychomotor symptoms in depression.

PMID- 9585731
TI  - Practice guideline for the treatment of patients with panic disorder. Work Group
      on Panic Disorder. American Psychiatric Association.

PMID- 9585732
TI  - International health services need an interorganizational policy.

PMID- 9585733
TI  - Cross-national comparisons of sexual behavior surveys--methodological
      difficulties and lessons for prevention.

PMID- 9585734
TI  - Unwanted pregnancy in Armenia--the larger context.

PMID- 9585735
TI  - Annotation: new rules for authorship in the journal: your contributions are
      recognized--and published!

PMID- 9585736
TI  - The globalization of public health, I: Threats and opportunities.
AB  - The globalization of public health poses new threats to health but also holds
      important opportunities in the coming century. This commentary identifies the
      major threats and opportunities presented by the process of globalization and
      emphasizes the need for transnational public health approaches to take advantage
      of the positive aspects of global change and to minimize the negative ones.
      Transnational public health issues are areas of mutual concern for the foreign
      policies of all countries. These trends indicate a need for cross-national
      comparisons (e.g., in the areas of health financing and policy development) and
      for the development of a transnational research agenda in public health.

PMID- 9585737
TI  - The globalization of public health, II: The convergence of self-interest and
      altruism.
AB  - The transnationalization of disease and health risks will require global
      awareness, analysis, and action and indicates a need for global cooperation.
      Transnational actions must be built on firm local and national foundations, but
      they also require new forms of transnational collaboration in order to minimize
      risks and build on opportunities. In a world characterized by the globalization
      of public health, countries and communities will need to look beyond their narrow
      self-interests in defining and confronting the shared problems that are emerging.
      In fact, a strong case can be made that enlightened self-interest and altruism
      will converge in the increasingly interdependent world being shaped by the
      process of globalization.

PMID- 9585738
TI  - Keeping competition fair for health insurance: how the Irish beat back risk-rated
      policies.
AB  - OBJECTIVES: This paper describes how Ireland created a level playing field for
      competition in health insurance, the strategies of a major insurer to introduce
      risk-rated policies that would segment the market, the successful campaign to
      block these policies, and the policy implications of the European Union
      requirement of competition in health insurance. METHODS: Policy documents,
      interviews, and press reports were analyzed. RESULTS: The minister of health
      forced the commercial insurer to withdraw its policies and replace them with
      community-rated policies. CONCLUSIONS: Because it is easier and more profitable
      for insurers to engage in risk selection than to become more efficient,
      beneficial competition in health insurance markets is extremely difficult to
      create. Carefully drawn rules and monitoring are required to overcome inherent
      causes of market failure. The current enthusiasm for saving money through
      competitive schemes in health insurance seems likely to produce higher costs and
      greater inequality.

PMID- 9585739
TI  - Private sexual behavior, public opinion, and public health policy related to
      sexually transmitted diseases: a US-British comparison.
AB  - OBJECTIVES: The purpose of this study was to characterize sexual behavior and
      opinions about sex in the United States and Britain; implications are discussed
      for effective public health policy regarding sexually transmitted diseases (STDs)
      in the United States. METHODS: Large-scale national probability surveys conducted
      in the 2 countries detailed sexual behavior, opinions, and the prevalence of
      STDs. RESULTS: In comparison with that of Britain, the US population has greater
      variability in sexual behavior, less tolerant opinions about sexual behavior, and
      a higher STD prevalence and lower condom usage among men. CONCLUSIONS: The survey
      data show compelling evidence from both countries of a strong association between
      number of sex partners and STD risk. In the United States relative to Britain,
      there is both greater dispersion in sexual behavior and a greater incidence of
      unconditional opposition to certain sexual practices. The former implies a need
      for strong public health policy to address the risks of STDs, but the latter
      implies strong opposition to that policy. This disjuncture between public health
      need and feasibility may contribute to the high US rate of STDs.

PMID- 9585740
TI  - From assurance to insurance in Russian health care: the problematic transition.
AB  - OBJECTIVES: Given the declining health status of the Russian population and the
      negative social impact of ongoing economic reforms, it is important to understand
      the nature and scope of Russia's innovations in health care financing. METHODS:
      Data on Russian health care and its financing were gathered from Russian
      newspapers and journals. US government agency reports, recent press accounts, and
      the authors' observations and interviews in Russia. RESULTS: The 1991 statutory
      basis for the Russian mandatory medical insurance system replaced the
      traditional, state-funded medical care system with a regional system principally
      reliant on an enterprise-based with-holding tax plus supplementation by local
      government and, to a minor extent, federal funds. The regional agent for
      distribution and management of these funds is a series of Territorial Health
      Insurance Funds. Implementation thus far has been highly uneven among
      territories. CONCLUSIONS: An insurance model patterned after the Western example
      may not be the optimal solution to Russia's current health financing problems.
      Given the chaotic nature of political and economic reform, Russia may simply not
      be ready for market-based medical insurance.

PMID- 9585741
TI  - Air pollution and daily mortality in Sydney, Australia, 1989 through 1993.
AB  - OBJECTIVES: This study examined the effects of outdoor air pollutants in Sydney,
      Australia, on daily mortality. METHODS: Time-series analysis was performed on
      counts of daily mortality and major outdoor air pollutants (particulates, ozone,
      and nitrogen dioxide) in Sydney (1989 to 1993) with adjustment for seasonal and
      cyclical factors. Poisson regression was calculated with allowance for
      overdispersion and autocorrelation. The effects of lagging exposure by 0 to 2
      days were assessed with single- and multiple-pollutant models. RESULTS: An
      increase in daily mean particulate concentration from the 10th to the 90th
      centile was associated with an increase of 2.63% (95% confidence interval 0.87 to
      4.41) in all-cause mortality and 2.68% (0.25 to 5.16) in cardiovascular
      mortality. An increase in daily maximum 1-hour ozone concentration from the 10th
      to the 90th centile was associated with an increase of 2.04% (0.37 to 3.73) in
      all-cause mortality and 2.52% (-0.25 to 5.38) in cardiovascular mortality. An
      increase in the daily mean nitrogen dioxide concentration from the 10th to the
      90th centile was associated with an increase of 7.71% (-0.34 to 16.40) in
      respiratory mortality. Multiple-pollutant models suggest that the effects of
      particulates and ozone on all-cause and cardiovascular mortality, and of nitrogen
      dioxide on respiratory mortality, are independent of the effects of the other
      pollutants. CONCLUSIONS: Current levels of air pollution in Sydney are associated
      with daily mortality.

PMID- 9585742
TI  - Mortality in a large population-based cohort of patients with drug-treated
      diabetes mellitus.
AB  - OBJECTIVES: This paper presents detailed cause-specific data about excess
      mortality among diabetic persons in Finland, by age and sex. METHODS: Five-year
      follow-up data on the Finnish population aged 30 through 74 years were analyzed.
      During these 5 years, 11,215 persons with diabetes and 102,843 persons without
      diabetes died. The diabetic population was defined as people who were entitled to
      free medication for diabetes at the beginning of the follow-up period, that is,
      at the end of 1980. RESULTS: The relative mortality of persons with drug-treated
      diabetes compared with nondiabetic persons was higher among women (3.4) than
      among men (2.4). Almost three quarters of the mortality excess was due to
      circulatory diseases. For most other causes of death, too, diabetic persons had
      higher than average mortality. The exceptions were lung cancer, chronic
      obstructive pulmonary disease, and alcohol poisoning. CONCLUSIONS: Diabetes is a
      general risk factor for untimely death and makes a significant contribution to
      overall national death rates, particularly for circulatory diseases. Lower than
      average mortality from smoking-related diseases and alcohol poisoning, however,
      warrant optimism about the effects of health education among diabetic persons.

PMID- 9585743
TI  - Use of chiropractic services from 1985 through 1991 in the United States and
      Canada.
AB  - OBJECTIVES: The purpose of this paper is to describe the demographic and clinical
      characteristics of chiropractic patients and to document chiropractic visit rates
      in 6 sites in the United States and Canada. METHODS: Random samples of
      chiropractors from 5 US sites and 1 Canadian site were selected. A record
      abstraction system was developed to obtain demographic and clinical data from
      office charts. RESULTS: Of the 185 eligible chiropractors sampled, 131 (71%)
      participated. Sixty-eight percent of the selected charts showed that care was
      sought for low back pain, while 32% recorded care for other reasons. Spinal
      manipulative therapy was recorded in 83% of all charts. There was a greater than
      2-fold difference in the median number of visits related to low back pain per
      episode of care across sites. The chiropractic visit rates in the US sites and
      Ontario are estimated to be 101.2 and 140.9 visits per 100 person-years,
      respectively. CONCLUSIONS: The chiropractic use rate in these sites is twice that
      of estimates made 15 years ago. The great majority of patients receive care for
      musculoskeletal conditions of the back and neck. The number of visits per episode
      varies appreciably by site.

PMID- 9585744
TI  - Increased cesarean section rates and emerging patterns of health insurance in
      Shanghai, China.
AB  - OBJECTIVES: This study examined the trend in cesarean section deliveries and the
      factors associated with it in the Minhang District of Shanghai, China. METHODS: A
      representative sample of the members of 2716 households in the district were
      interviewed in the fall of 1993. This study analyzed the data from 1959 married
      women of reproductive age with at least one live birth. RESULTS: During the past
      3 decades, the proportion of infants born by cesarean section increased from 4.7%
      to 22.5%. Logistic regression analysis revealed that the highest cesarean section
      rate, which occurred in the most recent period of 1988 through 1993, was
      associated with form of medical payment, self-reported complications during
      pregnancy, higher birthweight, and maternal age. Government insurance pays all
      costs of cesarean sections and accounted for the highest proportion of the
      cesarean section rate. CONCLUSIONS: The high rates of cesarean sections in China
      are surprising given the lack of the factors that usually lead to cesarean
      sections. The increasing cesarean section rates may be an early indication that
      emerging forms of health insurance and fee-for-service payments to physicians
      will lead to an excessive emphasis on costly, high-technology medical care in
      China.

PMID- 9585745
TI  - Fetal alcohol syndrome in Alaska, 1977 through 1992: an administrative prevalence
      derived from multiple data sources.
AB  - OBJECTIVES: The prevalence and characteristics of fetal alcohol syndrome cases
      and the usefulness of various data sources in surveillance were examined in
      Alaska to guide prevention and future surveillance efforts. METHODS: Sixteen data
      sources in Alaska were used to identify children with fetal alcohol syndrome.
      Medical charts were reviewed to verify cases, and records were reviewed to
      provide descriptive data. RESULTS: Fetal alcohol syndrome rates varied markedly
      by birth year and race, with the highest prevalence (4.1 per 1000 live births)
      found among Alaska Natives born between 1985 and 1988. Screening and referral
      programs to diagnostic clinics identified 70% of all recorded cases. The
      intervention program for children 0 to 3 years of age detected 29% of age
      appropriate cases, and Medicaid data identified 11% of all cases; birth
      certificates detected only 9% of the age-appropriate cases. CONCLUSIONS: Our
      findings indicate a high prevalence of fetal alcohol syndrome in Alaska and
      illustrate that reliance on any one data source would lead to underestimates of
      the extent of fetal alcohol syndrome in a population.

PMID- 9585746
TI  - Respiratory diphtheria in the United States, 1980 through 1995.
AB  - OBJECTIVES: The purpose of this study was to describe the epidemiologic,
      laboratory, and clinical features of respiratory diphtheria cases reported in the
      United States during 1980 through 1995. METHODS: Respiratory diphtheria cases
      reported to the Centers for Disease Control and Prevention were reviewed. Cases
      were defined as physician-diagnosed cases with signs and symptoms compatible with
      respiratory diphtheria, including the presence of a pseudomembrane without other
      apparent cause. RESULTS: From 1980 through 1994, 41 respiratory diphtheria cases
      were reported; none were reported in 1995, and no secondary cases were
      identified. Nine (22%) case patients were 4 years of age or younger, and 28 (68%)
      were 15 years of age or older. None of the case patients were up to date with
      diphtheria vaccination; 4 unvaccinated children died. Seventeen (43%) of 40 case
      patients had positive culture results. CONCLUSIONS: Available surveillance data
      suggest that respiratory diphtheria has become a rare disease in the United
      States. However, importation and circulation of toxigenic strains continue to
      present a threat and require achieving and maintaining high coverage with
      diphtheria toxoid-containing vaccines in both children and adults.

PMID- 9585747
TI  - Tuberculosis screening and compliance with return for skin test reading among
      active drug users.
AB  - OBJECTIVES: This study assessed the independent and combined effects of different
      levels of monetary incentives and a theory-based educational intervention on
      return for tuberculosis (TB) skin test reading in a sample of active injection
      drug and crack cocaine users. Prevalence of TB infection in this sample was also
      determined. METHODS: Active or recent drug users (n = 1004), recruited via street
      outreach techniques, were skin tested for TB. They were randomly assigned to 1 of
      2 levels of monetary incentive ($5 and $10) provided at return for skin test
      reading, alone or in combination with a brief motivational education session.
      RESULTS: More than 90% of those who received $10 returned for skin test reading,
      in comparison with 85% of those who received $5 and 33% of those who received no
      monetary incentive. The education session had no impact on return for skin test
      reading. The prevalence of a positive tuberculin test was 18.3%. CONCLUSIONS:
      Monetary incentives dramatically increase the return rate for TB skin test
      reading among drug users who are at high risk of TB infection.

PMID- 9585748
TI  - Smoking in the home: changing attitudes and current practices.
AB  - OBJECTIVES: Trends in attitudes and current practices concerning smoking in the
      home were examined. METHODS: Data from population-based surveys of adults in
      Ontario, Canada, were analyzed. RESULTS: Between 1992 and 1996, the percentage of
      respondents who agreed that parents spending time at home with small children
      should not smoke increased from 51% to 70%. In 1996, 34% of the homes surveyed
      were smoke-free. Smoke-free homes were associated with nonsmoking respondents and
      with the presence of children and no daily smokers in the home. Only 20% of homes
      with children and any daily smokers were smoke-free. CONCLUSIONS: Efforts are
      needed to assist parents in reducing children's exposure to environmental tobacco
      smoke in the home.

PMID- 9585749
TI  - Socioeconomic differences in the use of physician services in Nova Scotia.
AB  - OBJECTIVES: Socioeconomic differences in use of physician services in Nova
      Scotia, Canada were examined. METHODS: The study was based on survey data,
      containing information on socioeconomic status, linked to physician claims data.
      Socioeconomic differences in use of physician services were estimated, adjusted
      for age, sex, and region of residence. RESULTS: Large socioeconomic differences
      were observed in the use of physician services, with use inversely related to
      both household income and education. These differences remained after adjustment
      for age, sex, and region. CONCLUSIONS: Use of physician services is inversely
      associated with socioeconomic status.

PMID- 9585750
TI  - Contraception and induced abortion in Armenia: a critical need for family
      planning programs in eastern Europe.
AB  - OBJECTIVES: The purpose of this study was to determine the number of induced
      abortions per woman and the reasons for selecting induced abortion among parous
      Armenian women. METHODS: A consecutive series of 200 women attending an abortion
      clinic in Yerevan, Armenia, were queried by a physician about their reproductive
      histories. RESULTS: Women younger than 20 years of age reported a median of 1 and
      women older than 40 years reported a median of 8 induced abortions in their
      lifetimes (overall median = 3). Lack of contraceptive information was the major
      reason cited for not using contraception. CONCLUSIONS: Induced abortion is the
      major form of birth control among parous Armenian women. Concerted public health
      campaigns are needed to inform women and their physicians in Armenia and other
      Eastern European countries about alternative contraceptive methods.

PMID- 9585751
TI  - Anemia in young children of the Muynak District of Karakalpakistan, Uzbekistan:
      prevalence, type, and correlates.
AB  - OBJECTIVES: This study examined prevalence and correlates of anemia in the Muynak
      District of Uzbekistan, an area of rapidly changing social and economic
      conditions following the collapse of the Soviet Union. METHODS: Questionnaire
      data and blood samples were collected on a random sample of 433 children aged 1
      through 4 years. RESULTS: The prevalence of anemia ranged from 89% in 1-year-olds
      to 48% in 4-year-olds. Correlates for anemia included younger age, a communal
      water source, and a history of pica. CONCLUSIONS: Anemia is a widespread problem
      in young children in this district. An aggressive attempt to reverse this problem
      is needed.

PMID- 9585752
TI  - High birthweights among infants of north African immigrants in Belgium.
AB  - OBJECTIVES: This study examined birthweights of North African immigrants in
      Belgium. METHODS: Analyses focused on Belgian single live birth certificates from
      1981 to 1988. RESULTS: Low-birthweight (< 2500 g) rates were 3.1% among 34,686
      newborns of North African origin and 4.8% among 804,286 newborns of Belgian
      origin. The entire North African birthweight distribution was shifted toward
      higher birthweights than the Belgian distribution. Low frequencies of low
      birthweights among North Africans were still observed after marital status,
      occupation of the father, and parity had been taken into account. CONCLUSIONS:
      Despite their low socioeconomic status, North African immigrants have high
      birthweights.

PMID- 9585753
TI  - Effects of radon mitigation vs smoking cessation in reducing radon-related risk
      of lung cancer.
AB  - OBJECTIVES: The purpose of this paper is to provide smokers with information on
      the relative benefits of mitigating radon and quitting smoking in reducing radon
      related lung cancer risk. METHODS: The standard radon risk model, linked with
      models characterizing residential radon exposure and patterns of moving to new
      homes, was used to estimate the risk reduction produced by remediating high-radon
      homes, quitting smoking, or both. RESULTS: Quitting smoking reduces lung cancer
      risk from radon more than does reduction of radon exposure itself. CONCLUSIONS:
      Smokers should understand that, in addition to producing other health benefits,
      quitting smoking dominates strategies to deal with the problem posed by radon.

PMID- 9585754
TI  - Validity of insurance information on California birth certificates.
AB  - OBJECTIVES: This study assessed the validity of health insurance information on
      California birth certificates. METHODS: Insurance information from birth
      certificates and linked face-to-face interviews was compared for 7428 postpartum
      women in California. RESULTS: There was excellent agreement between insurance
      information in birth certificate and interview data, especially when capitated
      plans were grouped with all other private coverage. Analyses using both data
      sources produced similar estimates of the likelihood of untimely prenatal care
      according to type of insurance coverage. CONCLUSIONS: Birth certificate data
      including insurance information appear to be an appropriate resource for
      examining both the extent of coverage for maternity care and associations between
      prenatal care use and insurance status.

PMID- 9585755
TI  - Decrease in infant mortality in New York City after 1989.
AB  - OBJECTIVES: This study identified factors contributing to the rapid decline in
      infant mortality in New York City from 1989 to 1992. METHODS: Changes in
      birthweight distributions and in birthweight/age-, cause-, and
      birthweight/age/cause-specific mortality rates from 1988/89 (before the mortality
      reduction) to 1990/91 were identified from New York City vital statistics data.
      RESULTS: Infant, neonatal, and postneonatal mortality of very-low-birthweight (<
      1500 g) and normal-birthweight infants decreased significantly. The declines were
      almost entirely due to decreases in birthweight-specific mortality rates, rather
      than increased birthweights. All races experienced most of these reductions.
      Mortality decreased significantly for 6 causes of death. These decreases were
      consistent with the birthweight/age groups experiencing mortality declines.
      CONCLUSIONS: Widespread, multiple perinatal and postnatal factors contributed to
      the decline in infant mortality.

PMID- 9585756
TI  - Healthy valley 2000.

PMID- 9585757
TI  - Incorporating asthma education into a traditional school curriculum.

PMID- 9585758
TI  - Separating authorship responsibility and authorship credit: a proposal for
      biomedical journals.

PMID- 9585759
TI  - Multiple authorship for community intervention trials.

PMID- 9585760
TI  - If authors became contributors, everyone would gain, especially the reader.

PMID- 9585761
TI  - Correlation is not causation.

PMID- 9585762
TI  - A method for preserving confidentiality when linking computerized registries.

PMID- 9585764
TI  - Policy research: development process determines success.

PMID- 9585763
TI  - Are patients capable of attributing functional impairments to specific diseases?

PMID- 9585765
TI  - Politics and policy making.

PMID- 9585766
TI  - Mammography screening for women in their 40s: facilitating truly informed
      decision making.

PMID- 9585767
TI  - Mammography screening for women aged 40 through 49.

PMID- 9585768
TI  - Blunt injuries of the brachiocephalic artery.
AB  - Blunt injury of the brachiocephalic artery can pose diagnostic and management
      problems for the trauma and thoracic surgeon. To arrive at recommendations for
      dealing with this injury, we reviewed a seven-year experience at our trauma
      center. Between 1988 and 1995, five patients presented with blunt injuries of the
      brachiocephalic artery. All patients were stabilized and underwent repair through
      a median sternotomy with extension of the incision anterior to the
      sternocleidomastoid muscle. All patients had restoration of flow to the
      subclavian and carotid arteries utilizing bypass grafts (4) or primary repair
      (1). All patients survived to leave the hospital with no complications related to
      the procedure. Postoperative neurologic findings were present before the
      operative repair. Patients with blunt injuries of the brachiocephalic artery
      should be stabilized, and circulation of the subclavian and carotid arteries
      should be restored with graft placement or primary repair. Cardiopulmonary bypass
      and heparin or temporary shunts were not needed in this series of patients.
      Complications were related to associated injuries.

PMID- 9585769
TI  - Desmoid tumor arising in a laparoscopic trocar site.
AB  - Desmoid tumors are fibrotic neoplasms of low metastatic potential. These tumors
      have long been associated with major laparotomy incisions. However, to the best
      of our knowledge, they have not been previously associated with laparoscopic
      trocar placement. This report involves the case of a patient who developed a
      desmoid tumor at a trocar site. A 35 year-old premenopausal woman presented with
      an enlarging infraumbilical mass 10 years after a laparoscopic tubal ligation.
      The mass was immediately subjacent to the skin incision for the laparoscopic
      procedure. It was approximately 6 cm in diameter and fixed to the underlying
      abdominal wall. It was evaluated with sonographic and CT imaging, which revealed
      a solid mass arising from the fascia with no associated hernia. A biopsy of the
      mass confirmed a diagnosis of a desmoid tumor. This was subsequently excised with
      a wide margin and reconstructed with Marlex mesh. The patient is without
      recurrence 2 years following surgery. This case represents what we believe to be
      the first report of a desmoid tumor arising from a incision made for the
      placement of a laparoscopic port. Rapidly increasing laparoscopic applications
      make it likely that these lesions will increase in frequency. In this setting,
      resection with wide margins remains the mainstay of treatment for desmoid tumors.

PMID- 9585770
TI  - Minimally invasive parathyroidectomy for primary hyperparathyroidism: decreasing
      operative time and potential complications while improving cosmetic results.
AB  - Primarily because of the lack of highly accurate preoperative localizing studies,
      the standard operation for primary hyperparathyroidism (HPTH) has consisted of
      bilateral neck exploration with examination of all four parathyroid glands.
      Recent experience with the technetium-99m-Sestamibi scan at our hospital has
      suggested that this single test was now accurate enough to allow unilateral neck
      exploration. This study was designed to examine the efficacy and safety of
      minimally invasive parathyroid-ectomy in select patients with a single adenoma
      demonstrated on a preoperative sestamibi. Eighteen consecutive patients with
      primary HPTH in whom a sestamibi scan suggested a single adenoma underwent
      unilateral neck exploration through a 2.5-cm incision, which was extended as
      necessary. Results were compared to the preceding 25 parathyroid explorations for
      primary HPTH due to a single adenoma, which were nondirected and included
      bilateral neck exploration. All patients undergoing minimal exploration were
      found to have a single adenoma and demonstrated a normal serum calcium within 24
      hours of surgery. Standard bilateral exploration failed to locate the adenoma in
      one patient requiring subsequent re-exploration. Operative time, incision length,
      and length of hospital stay were all significantly less for those undergoing
      minimal exploration (all P < 0.01). There were no complications in either group.
      Minimally invasive neck exploration is a safe and effective treatment for primary
      HPTH, is easily accomplished under local anesthesia, and is associated with
      significant reductions in operative time and hospital stay. Limited exploration
      provides a better cosmetic result while decreasing the potential complications of
      bilateral exploration, but is dependent upon a high-quality sestamibi scan.

PMID- 9585771
TI  - Aggressive surgical management of necrotizing fasciitis serves to decrease
      mortality: a retrospective study.
AB  - Necrotizing fasciitis is an aggressive soft-tissue infection that in the past has
      carried a significant mortality rate. One of the most important determinants of
      outcome is recognition of the disease process. This is followed by aggressive
      resuscitation measures and radical debridement at the initial operation to
      control the infectious spread at the outset. The objective of this study is to
      help reveal the benefits of aggressive early surgical debridement in the
      treatment of necrotizing fasciitis. A retrospective review of the medical records
      of 68 patients between the years 1980 and 1996 with the diagnosis of necrotizing
      fasciitis was performed. The patients were assigned to two groups, Group A (21;
      31%), who had delay in therapy or inadequate preliminary therapy and Group B (47;
      69%), who underwent aggressive surgical debridement from the outset. Concomitant
      disease processes were noted. The medical records of 68 patients were studied.
      Age ranged from 13 to 67 (mean, 52) years of age. There were 38 (56%) females, 21
      (64%) of the patients were African-American, 24 (73%) of the patients had
      concomitant disease processes, 29 (42%) of the patients had a history of tobacco
      use, 11 (16%) of the patients had a history of alcohol consumption, and 11 (16%)
      of the patients were obese. Mortality in Group A was 8 of 21 patients (38%).
      Mortality in Group B was 2 of 47 patients (4.2%). The difference in mortality was
      found to be statistically significant (P = 0.0007). Early recognition and
      expeditious initial wide excision and debridement along with appropriate
      antibiotic coverage and support of systemic effects of necrotizing fasciitis
      serve to decrease morbidity and mortality. We believe the above is an absolute
      necessity followed by frequent washing and minor debridement of the wound until
      granulating tissue is observed. This can then be followed by procedures to
      close/cover the surgical defect (i.e., split-thickness skin grafts or various
      coverage flaps).

PMID- 9585772
TI  - Impact an anatomical site on bacteriological and clinical outcome in the
      management of intra-abdominal infections.
AB  - The clinical and bacteriological results of treatment for 429 patients who had
      intra-abdominal infection were analyzed to determine whether the anatomical
      origin of peritonitis influenced outcome. All patients had received effective
      broad spectrum antimicrobial therapy and operation in four multicenter trials.
      The diagnoses of infection were categorized into three sites: upper
      gastrointestinal tract, complicated appendicitis, and lower gastrointestinal
      tract. Clinical response rates were excellent for complicated appendicitis and
      were lowest for infections related to the upper gastrointestinal tract.
      Bacteriological response rates were also lower for upper gastrointestinal tract
      organisms and were highest for isolates associated with complicated appendicitis.
      There were no deaths in the 213 patients who had infection associated with
      appendicitis. Seven deaths occurred in the 86 patients (81%) with an upper
      gastrointestinal site of infection, and nine deaths occurred in the 130 patients
      (6.5%) with lower gastrointestinal site of infection. Mortality was related to
      recurrent intra-abdominal infection after an unsuccessful primary operation and a
      serum albumin less than 25 g/l. Clinical trails of antimicrobials for intra
      abdominal infection should consider stratification of patients according to these
      three levels of alimentary tract perforation when the site is known
      preoperatively. Patients who have infection secondary to previous surgery or who
      are malnourished represent a higher risk group even with appropriate antibiotics.

PMID- 9585773
TI  - Comparison of liver function tests after hepatic lobectomy and hepatic wedge
      resection.
AB  - Prior studies have suggested that changes in liver function tests may vary with
      the postoperative time interval and may be related to the extent of hepatic
      resection. This study describes characteristic profiles in parenchymal liver
      enzymes and other serum liver function tests over a 4-week course comparing
      anatomic to nonanatomic hepatic resections. The records of 48 patients undergoing
      successful major hepatic resection during a 3-year period were retrospectively
      reviewed. Of these 48 patients, 28 underwent formal anatomic resection (hepatic
      lobectomy), and 20 underwent nonanatomic resections (wedge resection). Routine
      postoperative management in lobectomy patients included drawing liver function
      tests and enzymes daily for the first week, then at approximately 2 and 4 weeks
      postoperatively. These tests included: prothrombin time (PT), partial
      thromboplastin time, total serum bilirubin, total protein (TP), aspartate
      transaminase, lactate dehydrogenase (LDH), alkaline phosphatase, albumin (A), and
      glucose. Patients undergoing wedge resections had these values checked less
      frequently, approximately 3 to 5 days, 2 weeks, and 4 weeks postoperatively.
      Profiles of these values were plotted over the 4-week postoperative time course
      for each group of patients. Patients undergoing hepatic lobectomy showed a
      characteristic laboratory value profile. PT elevated within 48 hours to a mean
      high of 16.0 seconds, then returned to normal by postoperative day 4. Partial
      thromboplastin time levels remained normal throughout the entire perioperative
      course. Total bilirubin rose slightly, to a mean high of 2.6 mg/100 cc, then
      returned to normal by postoperative day (POD) 14. Parenchymal liver enzymes
      aspartate transaminase and LDH rose abruptly to very high levels, then returned
      abruptly to normal (by POD 5). TP and A both fell to approximately 50 per cent of
      normal, gradually rising to normal by POD 14. Glucose rose to a mean high of 199
      mg/100 cc within the first 5 days, then returned to normal by POD 7. Alkaline
      phosphatase remained normal initially, then showed a progressive rise to a high
      of 288 mg/100 cc on POD 14. Patients undergoing wedge resections did not show the
      same changes in total serum bilirubin, but showed similar trends in all other
      tests, although the magnitude of these changes was smaller. TP and A levels fell
      acutely after resection, then began a slow rise toward normal by POD 21. TP and A
      profiles were similar for both lobectomy patients and those undergoing wedge
      resection. The only tests that may have altered clinical management were the PT
      and total bilirubin. Patients undergoing major hepatic resection have
      characteristic postoperative profiles of liver enzymes and liver function tests.
      These laboratory profiles differ with the extent of hepatic resection. The
      profiles reflect changes in volume status, parenchymal liver destruction,
      transient hepatic insufficiency, and postoperative hepatic regeneration. However,
      except possibly for PT and bilirubin, the routine use of these tests is not
      recommended, given that the results do not alter clinical management.

PMID- 9585774
TI  - Development of a novel synthetic material to close abdominal wall defects.
AB  - To compare the efficacy of a novel synthetic material (TMS-2) with
      polytetrafluoroethylene, polypropylene (Marlex), and primary closure of
      experimentally fashioned clean and contaminated abdominal wounds, 1-cm2 abdominal
      wall defects were created in each of the four abdominal quadrants of rats (n =
      10). Patches of each material were used to repair three of these defects, the
      fourth being primarily closed. A second group of rats (n = 7) underwent the same
      operative protocol; however, peritonitis was induced at the time of surgery using
      a fecal inoculation technique. Animals were killed 2 weeks later, and surface
      area and severity of formed adhesions were assessed by a "blinded" observer. All
      closure techniques were successful insofar as none demonstrated fascial
      dehiscence. Compared with each synthetic material, the surface area of formed
      adhesions was smaller after primary closure in clean and in contaminated
      conditions; however, the three synthetic materials were equally matched regarding
      surface area of adhesions under both conditions. In the face of fecal
      contamination, TMS-2 proved identical to primary closure, each generating
      significantly (P < 0.02) milder adhesions than the other prosthetic materials. It
      is concluded that the TMS-2 may prove of clinical benefit to repair abdominal
      wall defects.

PMID- 9585775
TI  - Efficacy of anticoagulation post-inferior vena caval filter placement.
AB  - Anticoagulation with heparin or Coumadin is usually effective in the management
      of deep vein thrombosis; however, if anticoagulation treatment is
      contraindicated, is ineffective, or leads to adverse effects, inferior vena caval
      (IVC) placement of a filter is indicated. The purpose of this study is to
      determine whether increased early adverse effects are present in patients not
      given anticoagulation medication after placement of an IVC filter. The records of
      240 consecutive patients who received IVC filter placement were reviewed for
      indications for placement, as well as for whether patients received
      anticoagulation medication on discharge. There were 41 in-patient mortalities. Of
      the remaining 199 patients, 100 were discharged and prescribed anticoagulation
      medication, and 99 were not. Patients were followed for 3 to 60 months. These
      results suggest that no early adverse effects are seen in patients who are not
      given anticoagulants after IVC filter placement.

PMID- 9585776
TI  - Omental transfer for salvage of the moribund lower extremity.
AB  - Use of omental flaps is well documented in soft tissue reconstruction of the head
      and neck, chest wall, and abdomen. Three cases of omental transfer for soft
      tissue reconstruction of the lower extremities are presented. In two patients,
      free vascularized omental flaps were used to cover deep soft tissue defects over
      the lower leg and in one patient, a pedicle flap was used to cover a deep groin
      defect extending into the hip joint. In all patients, use of an omental graft
      allowed revascularization and subsequent wound healing with good cosmetic
      results.

PMID- 9585777
TI  - Inflammatory breast carcinoma: comparison of survival of those diagnosed
      clinically, pathologically, or with both features.
AB  - There still remains some controversy as to whether or not there is a survival
      difference in patients with inflammatory breast carcinoma (IBC) with regard to
      whether they were diagnosed clinically, pathologically, or with both features. We
      conducted a retrospective chart review of all the patients diagnosed with IBC who
      were treated at the Nova Scotia Cancer Treatment and Research foundation between
      the years of 1990 and 1994, inclusive. Fifty-seven patients' charts were reviewed
      for recurrence or death up until Feb. 16, 1996. The overall survival of the 57
      patients was 32 per cent (confidence interval, 16-48%) and 12 per cent
      (confidence interval, 0-26%) at 3 and 5 years, respectively. The survival times
      according to presentation (clinical, pathological, or both) at 3 and 5 years were
      31 and 10 per cent for the clinically diagnosed group, 56 per cent at 3 years for
      the pathologically diagnosed group (5-year survival times could not be
      calculated), and 34 and 20 per cent for the group diagnosed both clinically and
      pathologically, respectively. Analysis by the log-rank test revealed that there
      was no significant difference in survival between these three groups. We conclude
      that there was no statistically significant difference in survival between those
      patients who presented clinically, pathologically, or with both features.

PMID- 9585778
TI  - Effect of dopamine on renal function after arteriography in patients with pre
      existing renal insufficiency.
AB  - Contrast media-induced nephropathy is one of the leading causes of hospital
      acquired renal failure, occurring most frequently in patients with pre-existing
      renal insufficiency. We prospectively studied 55 patients with chronic renal
      insufficiency (serum creatinine concentration 1.4 to 3.5 mg/dl) who underwent
      abdominal aortography and arteriography of the lower extremities. The patients
      were randomized into two groups. Group 1, 28 patients, received dopamine 2.5
      mcg/kg beginning 1 hour before arteriography and continuing for 12 hours. Group 2
      received an equal volume of saline for the same period of time. Serum creatinine
      and 12-hour creatinine clearance were measured before arteriography and for 4
      consecutive days afterward. Acute contrast-induced decrease in renal function was
      defined as increase in the baseline serum creatinine concentration > or = 0.5
      mg/dl. On day 1 postarteriography the serum creatinine increased from baseline
      .193 mg/dl for controls while the dopamine group decreased slightly from baseline
      .018 mg/dl (p = 0.002). Excepting day 1 postarteriography, there was no
      statistical difference between groups, and serum levels for both groups increased
      linearly from baseline across time (dopamine p = 0.028, control p = 0.025). In
      patients with pre-arteriography baseline serum levels greater than or equal to
      2.0 mg/dl, however, the increase in serum creatinine from baseline levels was
      consistently and significantly greater in the control group through the fourth
      day (0.012 < or = p < or = 0.049). Creatinine clearance did not change
      significantly from baseline after arteriography in the dopamine group (baseline
      versus days 1 through 4, 0.238 < or = p < or = 0.968); however, the control group
      showed a significant linear decrease in creatinine clearance from baseline
      through the fourth day after arteriography (p = 0.016). Dopamine infusion
      prevented a rise in serum creatinine 24 hours after angiography in patients with
      pre-existing renal insufficiency, and protected against contrast-induced decrease
      in renal function in patients whose baseline serum creatinine was > or = 2.0
      mg/dl.

PMID- 9585779
TI  - Prognostic factors for adenocarcinoma of the gallbladder: an analysis of 162
      cases.
AB  - Carcinoma of the gallbladder is a rare neoplasm and is associated with a dismal
      prognosis. To analyze the natural history of this disease and prognostic factors,
      a large tumor registry database was accessed. During the period 1972 to 1995, 214
      patients were entered. Adequate follow-up was available on 162 patients, and this
      group forms the basis of this review. There were 54 males and 108 females with a
      median age of 62 years. Median follow-up was 7 months. Right upper quadrant
      abdominal pain was the most frequent presenting symptom. Fifteen patients had an
      incidental finding of carcinoma after cholecystectomy. Overall, 5-year survival
      was 25 per cent, with a median survival time of 9.7 months. Survival was improved
      for patients with local disease compared with those with regional or metastatic
      disease. One hundred nine patients underwent surgical therapy. Complete resection
      was possible in 36 patients, whereas 44 patients had residual disease. Median
      survival time for patients with no residual disease was 67.2 months, whereas
      those for patients with microscopic residual tumor and gross residual tumor were
      8.9 and 3.8 months, respectively (P < 0.000001). Gallbladder cancer is often
      diagnosed at an advanced stage and is associated with a poor prognosis. In
      patients with localized disease, surgical treatment provides the opportunity for
      long-term survival only when a complete resection can be performed. Prognosis for
      patients with microscopic residual and gross residual disease is similar.

PMID- 9585780
TI  - Gallbladder hypokinesia: an unusual cause of duodenal obstruction.
AB  - Gallbladder hypokinesis is an uncommon condition and a potential etiologic factor
      in the formation of gallstones and the development of cholecystitis. It is
      associated with a number of different conditions, but gallbladder hypokinesia as
      a cause of small bowel obstruction is unreported. In the case presented below, we
      saw a postoperative partial upper small bowel obstruction due to hypokinesia of
      the gallbladder. The investigations, management, and subsequent recovery are
      described. A review of the literature failed to reveal any similar occurrence.

PMID- 9585781
TI  - Bedside percutaneous tracheostomy in acquired immunodeficiency syndrome.
AB  - Tracheostomy tube insertion is periodically performed when patients with acquired
      immunodeficiency syndrome (AIDS) require prolonged mechanical ventilation. In
      this population, bedside percutaneous tracheostomy may be a better technique than
      conventional operating room tracheostomy because it reduces procedural cost,
      requires no patient transport, and requires few sharp instruments, thereby
      potentially decreasing risk to surgical staff. A retrospective review was
      conducted in the Department of Medical Records at St. Vincents Hospital and
      Medical Center of New York City. Nine consecutive patients diagnosed with AIDS
      and undergoing percutaneous tracheostomy from January 1, 1992, to December 31,
      1996, were identified. All patients were males (mean age 32.1 +/- 4 years, CD4
      count average 145) and were ventilator-dependent for mean of 24 +/- 3 days. The
      procedure was successful and without complications in all patients. Follow-up was
      27 months (range 1-42 months) and in-hospital mortality was 77 per cent. The
      average length of survival for those patients who died in the hospital was 29
      days (range, 3-120). Two patients survived the hospitalization after undergoing
      decannulation on postoperative days 29 and 52, respectively. Despite the poor
      prognosis after tracheostomy in patients with AIDS this procedure allows better
      oral care and may improve patient comfort. Bedside percutaneous tracheostomy can
      be performed with less risk to surgical personnel and patient when compared to
      conventional surgery. This minimally invasive procedure safely and efficiently
      provides prolonged tracheal access in patients with AIDS.

PMID- 9585782
TI  - HIV infection among rural trauma patients: a blind serosurvey and literature
      review.
AB  - Human immunodeficiency virus (HIV) seroprevalence rates among rural trauma
      patients range between 0.15 and 1.32 per cent. A random sample of trauma patients
      treated at our rural trauma center between September 1994 and November 1995 was
      enrolled into a blind HIV serosurvey. Five hundred sixty-six of 1315 trauma
      patients (43%) were tested. Two of the 566 patients (0.35%) were HIV positive. A
      review of aggregate data for HIV infection among rural trauma patients in the
      United States show that 28 of the 4639 patients (0.60%) are HIV positive. We
      conclude that there was a low HIV incidence among our trauma patients from
      September 1994 to November 1995, and the cost-effectiveness of HIV testing for
      rural trauma patients is questionable with incidences between 0.5 and 1.0 per
      cent.

PMID- 9585783
TI  - Blunt splenic trauma: characteristics of patients requiring urgent laparotomy.
AB  - In victims of blunt abdominal trauma, the spleen is the most common organ
      damaged, it is the most likely source of serious injury, and is associated with
      significant morbidity and mortality. The participants in this study were
      emergency department (ED) patients with splenic trauma determined via imaging
      study, surgical exploration, or autopsy. Patients were located using both the
      institution's trauma registry and discharge diagnoses (ICD-9 codes) involving
      splenic injury resulting from blunt trauma. Medical records including pre
      hospital, ED, and hospital information were reviewed. Chi Square and Fisher's
      exact test were used for statistical analysis where appropriate, with a P value
      of less than 0.05 considered significant. Fifty-five patients (60% male) were
      analyzed with a mean age of 31 years (range, 1 to 78 years). Sixteen (30%)
      patients (mean age 44 years) were managed operatively, with 14 patients receiving
      only a diagnostic peritoneal lavage. All 38 patients (70%, mean age 26 years) who
      received nonoperative management were diagnosed by computed tomography. The motor
      vehicle crash represented the most frequent mechanism of injury in both groups;
      the nonoperative group, however, experienced other injury mechanisms more
      frequently. Clinical variables suggestive of the need for urgent surgical
      intervention (from ED to the surgical suite) include hypotension (systolic blood
      pressure less than 90 mm/Hg) in the pre-hospital setting or ED; tachycardia
      (heart rate greater than 100 beats/min) in the ED; abnormal hematocrit (less than
      30) or coagulopathy (prothrombin time greater than 14 seconds) in the ED;
      multiple injuries; or blood transfusion in the ED. Complaints of pain resulting
      from traumatic injury and abdominal examination findings did not identify
      patients requiring urgent operative management. Hemodynamic instability, evidence
      of multiple injuries, abnormal laboratory parameters, and the requirement for
      blood transfusion in the ED identifies a patient population likely to require
      operative therapy of their splenic injury. Emergency physicians should consider
      early surgical consultation or urgent transfer to the regional trauma center in
      patients with these characteristics.

PMID- 9585784
TI  - Assessment of ventilation during the performance of a percutaneous dilatational
      tracheostomy: hypoventilation is not a common complication.
AB  - Percutaneous dilatational tracheostomy (PDT) is becoming an accepted cost
      effective alternative to surgical tracheostomy. PDT is performed by progressive
      dilatation of a tracheal opening placed under bronchoscopic guidance. Case
      reports of hypoventilation with associated hypercarbia during the performance of
      PDT have raised concerns about the utility of this procedure in patients in whom
      hypercarbia is problematic (e.g., patients with closed head injury). In a
      prospective cohort analysis of 11 critically ill patients, we evaluated the
      effect of PDT on ventilation during and after the procedure using end tidal
      capnography. We found that hypercarbia does not occur during or after the
      performance of PDT as compared to baseline levels.

PMID- 9585785
TI  - Necrotizing fasciitis after tumescent liposuction.
AB  - We report a case of necrotizing fasciitis after tumescent liposuction, a new and
      increasingly popular plastic surgery procedure. After radical surgical
      debridement and staged full-thickness skin grafting, the patient ultimately
      recovered. The significance and recognition of this serious complication is
      emphasized.

PMID- 9585786
TI  - The prevalence and effect of alcohol and drug abuse on cohort-matched critically
      injured patients.
AB  - A prospective study was undertaken at a Level I trauma center to evaluate the
      prevalence of substance use among victims of major trauma, along with the impact
      on clinical outcome. Five hundred sixteen patients had urine toxicology and blood
      alcohol screens performed and correlated with pattern and severity of injury,
      hospital course, and outcome. Three hundred seventy-one patients (71%) screened
      positive for alcohol or drugs, or both. Fifty-two per cent had positive alcohol
      screens, and 42 per cent had positive drug screens (cocaine and opiates
      represented 91% of positive drug screens). Univariate analysis revealed patterns
      of alcohol/drug use varied among subgroups according to demographics (less use
      among patients older than 55 years, females and Asians; more drug use in blacks;
      more alcohol use in Hispanics), mechanism of injury (non-use in blunt trauma
      patients and use of both in penetrating trauma patients) and body region injured
      (non-use in head-injured patients). Septic complications and mortality were more
      correlative with severity of injury, but not with use or non-use of alcohol or
      drugs. We conclude that alcohol and drug use remains a major comorbid factor in
      major trauma, and that injury prevention efforts should include a strong focus on
      counseling regarding these lifestyle choices.

PMID- 9585787
TI  - Solitary scapula mass: atypical presentation of esophageal adenocarcinoma.
AB  - Adenocarcinoma of the esophagus is an aggressive malignancy that frequently
      occurs with lymph node involvement. Current management strategies may incorporate
      adjuvant therapeutic modalities in an attempt to improve the typical dismal
      outcome. There is frequent association of esophageal adenocarcinoma with Barret's
      metaplasia. Isolated bone and soft tissue metastases are rare and may present a
      diagnostic challenge in asymptomatic patients.

PMID- 9585788
TI  - Acute acalculous cholecystitis: incidence, risk factors, diagnosis, and outcome.
AB  - The objective of this study was to review the incidence, risk factors, methods of
      diagnosis, and outcome of acute acalculous cholecystitis (AAC) and to identify
      the sensitivity and limitations of current radiographic modalities used to
      establish the diagnosis. Our study was a retrospective chart review in a tertiary
      care university hospital. Over a 53-month period, 27 cases of AAC (17 males, 10
      females; mean age 50 years; mean Acute Physiology and Chronic Health Evaluation
      II score, 17) were encountered. Of these, 14 (52%) occurred in critically ill
      patients and 17 (63%) in patients recovering from non-biliary tract operations.
      AAC occurred in 0.19 per cent of surgical intensive care unit admissions and
      accounted for 14 per cent (27 of 188) of all cases of acute cholecystitis.
      Presenting symptoms and laboratory values were nonspecific. Twenty patients had
      radiographic studies before surgery. Among the various radiological studies used
      for AAC, morphine cholescintigraphy had the highest sensitivity (9 of 10; 90%),
      followed by computed tomography (8 of 12; 67%) and ultrasonography (2 of 7; 29%).
      Ten of the 20 patients had more than one study done preoperatively. All 27
      patients had an open cholecystectomy. AAC was associated with a high incidence of
      gangrene (17 of 27 cases; 63%), perforation (4 of 27; 15%), and abscess (1 of 27;
      4%). The mortality rate was 41 per cent (11 of 27). We conclude that AAC is a
      rare, but potentially lethal, disease occurring in critically ill patients and
      those recovering from non-biliary tract operations. The clinical presentation is
      nonspecific, and significant delays in diagnosis result in a high incidence of
      gangrene, perforation, abscess, and death. To improve outcome, a high index of
      suspicion with early radiographic evaluation, often employing multiple studies,
      is necessary. An algorithm for the evaluation of patients for suspected AAC is
      proposed.

PMID- 9585789
TI  - The Little Rock weave.
AB  - A debate has raged in the surgical literature about the use of a running suture
      verses interrupted sutures for abdominal wound closures. For most abdominal
      wounds either method can probably be used safely. A modified interrupted
      technique is described which may be useful for some difficult wounds. One of the
      main advantages of this technique is that the wound tension is equally
      distributed along the entire wound and not only on the last placed suture. The
      sutures are easily tied without having "to fight the wound".

PMID- 9585790
TI  - Fogarty and his catheter.

PMID- 9585791
TI  - Re: Intermittent subacute intestinal obstruction due to a giant lipoma of the
      colon: a case report.

PMID- 9585792
TI  - Clinical pathways for general surgeons: elective colectomy for cancer.

PMID- 9585793
TI  - Grapefruit juice greatly increases serum concentrations of lovastatin and
      lovastatin acid.
AB  - BACKGROUND: Grapefruit juice increases the bioavailability of several drugs known
      to be metabolized by CYP3A4. We wanted to investigate a possible interaction of
      grapefruit juice with lovastatin, a cholesterol-lowering agent that is partially
      metabolized by CY P3A4. METHODS: An open, randomized, two-phase crossover study
      with an interval of 2 weeks between the phases was carried out. Ten healthy
      volunteers took either 200 ml double-strength grapefruit juice or water orally
      three times a day for 2 days. On day 3, each subject ingested 80 mg lovastatin
      with either 200 ml grapefruit juice or water, and an additional dose of 200 ml
      was ingested 1/2 and 1 1/2 hours after lovastatin intake. Serum concentrations of
      lovastatin and lovastatin acid were measured up to 12 hours. RESULTS: Grapefruit
      juice greatly increased the serum concentrations of both lovastatin and
      lovastatin acid. The mean peak serum concentration (Cmax) of lovastatin was
      increased about 12-fold (range, 5.2-fold to 19.7-fold; p < 0.001) and the area
      under the concentration-time curve [AUC(0-12)] was increased 15-fold (range, 5.7
      fold to 26.3-fold; p < 0.001) by grapefruit juice. The mean Cmax and AUC(0-12) of
      lovastatin acid were increased about fourfold (range, 1.8-fold to 11.5-fold; p <
      0.001) and fivefold (range, 2.4-fold to 23.3-fold; p < 0.001) by grapefruit
      juice, respectively. The half-lives of lovastatin and lovastatin acid remained
      unchanged. CONCLUSIONS: Grapefruit juice can greatly increase serum
      concentrations of lovastatin and its active metabolite, lovastatin acid, probably
      by preventing CYP3A4-mediated first-pass metabolism in the small intestine. The
      concomitant use of grapefruit juice with lovastatin and simvastatin should be
      avoided, or the dose of these 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors should be reduced accordingly.

PMID- 9585794
TI  - Pharmacokinetic and pharmacodynamic interactions between fluoxetine and
      moclobemide in the investigation of development of the "serotonin syndrome".
AB  - OBJECTIVE: To assess the tolerability, safety, pharmacokinetics, and
      pharmacodynamics of combined treatment with fluoxetine and moclobemide in healthy
      subjects. METHODS: Fluoxetine (20 to 40 mg/day) was administered for 23 days to
      18 subjects. At (nor)fluoxetine steady state, subjects were randomized in a 2:1
      ratio to receive in addition either moclobemide (ascending doses up to 600
      mg/day) of placebo. A single 300 mg dose of moclobemide was administered before
      and at the end of the fluoxetine regimen to assess the effects of the latter on
      the pharmacokinetics and pharmacodynamics of moclobemide. Adverse events and
      vital signs were recorded and pharmacokinetic parameters of fluoxetine and
      moclobemide were determined. Plasma concentrations of 3,4-dihydroxy-phenyl
      glycol, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and serotonin
      uptake into platelets were assessed as pharmacodynamic measures. RESULTS: The
      number, intensity, or type of adverse events did not change when moclobemide was
      added to fluoxetine. No clinically relevant changes in safety parameters
      occurred. Fluoxetine markedly inhibited the metabolism of moclobemide. However,
      multiple dosing of moclobemide did not lead the excessive accumulation. 3,4
      Dihydroxyphenylglycol, 5-hydroxyindoleacetic acid, and 3,4-dihydroxyphenylacetic
      acid plasma levels and serotonin uptake did not reveal a pharmacodynamic
      interaction. CONCLUSIONS: Combination treatment with fluoxetine and moclobemide
      did not provide any indication of development of the "serotonin syndrome."

PMID- 9585795
TI  - The effect of multiple doses of ritonavir on the pharmacokinetics of rifabutin.
AB  - OBJECTIVE: To investigate the effects of ritonavir on the pharmacokinetics of
      rifabutin. METHODS: In a multiple-dose, randomized, parallel-group, double-blind
      study, subjects received 150 mg rifabutin daily for 24 days coadministered on
      days 15 to 24 with twice-daily doses of either placebo or ritonavir (300 mg on
      day 15, 400 mg on day 16, and 500 mg on days 17 to 24). Plasma concentrations of
      rifabutin and 25-O-desacetylrifabutin were measured by HPLC, and the
      pharmacokinetics were determined after the rifabutin doses on days 14 and 24.
      RESULTS: For subjects receiving rifabutin and placebo who completed the study (n
      = 11), there were small but statistically significant differences (< or = 32%) in
      several rifabutin and 25-O-desacetylrifabutin pharmacokinetic parameters between
      the regimens of rifabutin alone and rifabutin with placebo. In contrast, the
      effect of ritonavir on rifabutin pharmacokinetics of subjects completing the
      study (n = 5) was substantial. Rifabutin mean minimum observed concentration
      (Cmin), maximum observed concentration (Cmax), and area under the concentration
      time curve [AUC(0-24)] increased by approximately sixfold, 2.5-fold, and
      fourfold, respectively, and 25-O-desacetylrifabutin mean Cmin, Cmax, and AUC(0
      24) increased by approximately 200-, 16-, and 35-fold, respectively, when
      coadministered with ritonavir compared with rifabutin administered alone. The sum
      of the mean AUC(0-24) of rifabutin and 25-O-desacetylrifabutin increased nearly
      sevenfold when coadministered with ritonavir. CONCLUSIONS: Ritonavir inhibited
      the metabolism of rifabutin and 25-O-desacetylrifabutin, suggesting that both are
      metabolized at least in part by CYP3A. Ritonavir may have enhanced rifabutin
      bioavailability by reducing either intestinal of hepatic metabolism of both.
      Clarithromycin is an alternative to rifabutin for antimycobacterial therapy that
      may be administered concurrently with ritonavir. Administration of ritonavir with
      a reduced rifabutin dosage regimen (150 mg every Monday, Wednesday, and Friday)
      is being investigated.

PMID- 9585796
TI  - Genetic polymorphism of the hepatic cytochrome P450 2C19 in north Indian
      subjects.
AB  - One hundred unrelated healthy North Indian subjects were phenotyped with respect
      to their ability to metabolize omeprazole to 5-hydroxyomeprazole. Each volunteer
      was requested to ingest 20 mg (57.9 mumol) omeprazole. Urine was collected for a
      period of 8 hours and the amount of 5-hydroxyomeprazole excreted was estimated by
      HPLC. Histogram, probit, and normal test variable plots showed the antimode value
      for the log hydroxylation index of omeprazole to be 1.7. Of 100 North Indian
      subjects, 11 demonstrated log hydroxylation index values more than 1.7. Thus it
      is inferred that the frequency of occurrence of poor metabolizers of omeprazole
      in North Indian subjects is 11% (95% confidence interval, 5% to 17%). From the
      Hardy-Weinberg Law it was computed that the frequency of occurrence of the mutant
      allele of hepatic CYP2C19 in the North Indian subjects was 0.33.

PMID- 9585797
TI  - Blunted 5-HT1A-receptor agonist-induced corticotropin and cortisol responses
      after long-term ipsapirone and fluoxetine administration to healthy subjects.
AB  - OBJECTIVES: To assess whether acute 5-hydroxytryptamine-1A (5-HT1A)-receptor
      mediated corticotropin, cortisol, and temperature responses are maintained after
      3 weeks of treatment with controlled-release (CR) ipsapirone and fluoxetine
      compared with placebo and whether changes are reversible after cessation of
      treatment. METHODS: This was a randomized parallel-group study. Ten healthy
      subjects received ipsapirone CR or fluoxetine, and eight received placebo in a
      double-blind manner. An ipsapirone challenge test with 20 mg ipsapirone immediate
      release formulation (IR) was performed before treatment (day 0) and after 20 days
      of treatment with placebo, 80 mg/day ipsapirone CR, or 20 mg/day fluoxetine (day
      21). From day 22 to day 34 all subjects received placebo in a simple-blind
      manner. A third ipsapirone challenge test was performed on day 35. RESULTS:
      Before treatment, resting plasma corticotropin and cortisol concentrations and
      increases in plasma corticotropin and cortisol concentrations after challenge
      with 20 mg ipsapirone IR were similar for the three groups. After 20 days of
      treatment, plasma corticotropin and cortisol concentrations were similar before
      challenge, but ipsapirone IR-induced increases in plasma corticotropin and
      cortisol concentrations were significantly lower in both the ipsapirone CR group
      (corticotropin, 6.5 +/- 2 pg/ml; cortisol, 1.5 +/- 0.7 micrograms/dl) and
      fluoxetine group (corticotropin 4.4 +/- 2 pg/ml; cortisol 1.5 +/- 0.7
      micrograms/dl) compared with placebo (corticotropin, 34 +/- 14 pg/ml; cortisol,
      5.8 +/- 2 micrograms/dl, mean +/- SEM). After 2 weeks of placebo administration,
      plasma corticotropin and cortisol responses to ipsapirone IR again became
      identical in all three groups. Plasma ipsapirone concentrations were similar in
      all groups during each challenge. The hypothermic response to ipsapirone IR
      showed no difference before treatment, at the end of the treatment period, or 2
      weeks after cessation of treatment. Long-term administration of antidepressants
      to the healthy subjects did not lead to any serious adverse effects. CONCLUSIONS:
      Long-term administration of fluoxetine and ipsapirone did not influence resting
      plasma corticotropin and cortisol concentrations in the morning. Stimulation of
      corticotropin and cortisol release by a selective 5-HT1A-agonist is reduced with
      long-term administration of these serotoninergic antidepressants. This
      subsensitivity of postsynaptic 5-HT1A-receptors is reversible.

PMID- 9585798
TI  - Can bioavailability of low-variance drugs be estimated with an unpaired, sparse
      sampling design?
AB  - OBJECTIVE: Bioavailability (F) with nonintravenous administration is
      traditionally estimated by comparison of the area under the plasma concentration
      versus time curve (AUC) after drug administration by each of the nonintravenous
      and intravenous routes in the same individual. This paired approach may not
      always be possible. We simulated whether F and the absorption rate constant (ka)
      could be estimated accurately for a drug with low variance using different
      patients for nonintravenous and intravenous routes and whether sparse sampling
      permitted accurate estimates. METHODS: Using pharmacokinetic parameters for
      cisatracurium besylate (INN, cisatracurium besilate), we simulated data sets
      representing 20 administrations (10 intravenous and 10 nonintravenous) with
      either three (sparse) or 16 (extensive) samples per administration. Simulations
      were performed twice, with ka values of 0.1 (slow absorption) or 0.3 (rapid
      absorption) min-1. With use of NONMEM, we estimated F and ka for each data set
      using both two-stage and mixed-effects modeling approaches and paired and
      unpaired designs to determine the percentage of estimates that deviated > 25%
      from the simulated value. RESULTS: Estimates of F with extensive data were
      satisfactory for all approaches. With sparse sampling, two-stage analysis of
      unpaired data were not possible, two-stage analysis of paired data yielded
      erroneous estimates, and mixed-effects modeling gave satisfactory estimates.
      Estimates of ka were sometimes erroneous with all approaches except for paired
      analysis of extensive data with slow absorption; sparse data and two-stage
      analysis increased the likelihood of errors compared with extensive data and
      mixed-effects modeling. CONCLUSIONS: Mixed-effects modeling facilitates
      estimation of F and ka for low-variance drugs in situations in which traditional
      paired extensive data designs are not possible.

PMID- 9585799
TI  - 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13
      functional CYP2D6 genes.
AB  - OBJECTIVE: To investigate the disposition and effects of nortriptyline and its
      major metabolite 10-hydroxy-nortriptyline line in panels of white subjects with
      different CYP2D6 genotypes, including those with duplicated and multiduplicated
      CYP2D6*2 genes and to evaluate the contribution of the number of functional C
      gamma P2D6 alleles to the metabolism of nortriptyline, used here as a model drug
      for CYP2D6 substrates. METHODS: Oral single doses of 25 to 50 mg nortriptyline
      were given to five poor metabolizers of debrisoquin (INN; debrisoquine) with no
      functional CYP2D6 gene, five extensive metabolizers with one functional CY2D6
      gene, five extensive metabolizers with two functional CYP2D6 genes, five
      ultrarapid metabolizers with duplicated CYP2D6*2 genes, and one ultrarapid
      metabolizer with 13 copies of the CYP2D6*2 gene. Plasma kinetics of nortriptyline
      and 10-hydroxynortriptyline were analyzed. Anticholinergic effects (inhibition of
      salivation and accommodation disturbances), sedation, blood pressure, and effect
      on supine and erect pulse rate were measured. RESULTS: There was a clear relation
      between the C gamma P2D6 genotype and the plasma kinetics of nortriptyline and 10
      hydroxynortriptyline. The proportion between the apparent oral clearances of
      nortriptyline in the groups with 0, 1, 2, 3, and 13 functional genes was
      1:1:4:5:17. The proportions between AUC(nortriptyline) to AUC(10
      hydroxynortriptyline) ratios in the groups with 0, 1, 2, 3, and 13 functional
      genes were 36:25:10:4:1. Oral plasma clearance of nortriptyline and
      AUC(nortriptyline) to AUC(10-hydroxynortriptyline) ratio both correlated
      significantly with the debrisoquin metabolic ratio (rS = -0.89, p = 0.0001; rS =
      0.92, p = 0.0001). Although ultrarapid metabolizer subjects were given double the
      nortriptyline dose (50 mg), inhibition of salivation was not more pronounced
      compared with the other genotype groups given 25 mg nortriptyline. CONCLUSION:
      The results of this study show the quantitative importance of the CYP2D6
      genotype, especially the presence of multiple functional CYP2D6 genes for the
      pharmacokinetics of nortriptyline and 10-hydroxynortriptyline. Genotyping of
      subjects with multiple copies of functional genes may be of great value for
      differentiating ultrarapid metabolizers from patients who do not comply with the
      prescription and for assuring adequate drug choice and dosage for these patients.

PMID- 9585800
TI  - Pharmacokinetic interactions between two human immunodeficiency virus protease
      inhibitors, ritonavir and saquinavir.
AB  - OBJECTIVE: To assess the pharmacokinetic interaction between ritonavir and
      saquinavir. METHODS: Ritonavir and saquinavir were administered in single doses
      to six groups of healthy volunteers in a two-way (saquinavir alone and ritonavir
      plus saquinavir for groups I through V) and a three-way (ritonavir alone,
      saquinavir alone, and ritonavir plus saquinavir for group VI) crossover manner
      with the following doses: group I, 200 mg saquinavir and 300 mg ritonavir; group
      II, 200 mg saquinavir and 600 mg ritonavir; group III, 400 mg saquinavir and 300
      mg ritonavir; group IV, 400 mg saquinavir and 600 mg ritonavir; group V; 600 mg
      saquinavir and 200 mg ritonavir; group VI, 600 mg saquinavir and 600 mg
      ritonavir. RESULTS: Coadministration of ritonavir markedly increased the area
      under the plasma concentration-time curve (AUC) and peak concentration of
      saquinavir (> 50-fold and 22-fold, respectively). For a constant ritonavir dose,
      the pharmacokinetics of saquinavir were relatively proportional to dose. For a
      constant saquinavir dose, the increase in saquinavir concentration tended to be
      less than proportional to ritonavir dose. Ritonavir reduced intersubject
      variability in the saquinavir AUC from 60% to 28%. The in vivo inhibition
      constant was 0.025 +/- 0.020 micrograms/ml with noncompartmental estimation and
      0.0164 +/- 0.0004 micrograms/ml with nonlinear mixed-effects model compartmental
      analysis. Saquinavir showed no clinically significant effect on the
      pharmacokinetics of ritonavir (+6.4% in AUC). The regimens were well tolerated.
      CONCLUSIONS: The large effect of ritonavir on the pharmacokinetics of saquinavir
      is consistent with a large reduction of saquinavir first-pass metabolism and
      postabsorptive clearance. Given the limited bioavailability of saquinavir given
      in the hard gelatin capsule formulation, this drug interaction is expected to
      have implications in the use of protease inhibitors in the management of human
      immunodeficiency virus infection.

PMID- 9585801
TI  - Individual pharmacodynamics assessed by antilymphocyte action predicts clinical
      cyclosporine efficacy in psoriasis.
AB  - BACKGROUND: Cyclosporine (INN, ciclosporin) use for psoriasis has been proposed
      and clinically examined. However, individual variation in cyclosporine efficacy
      is currently observed. To evaluate individual therapeutic potency of
      cyclosporine, pharmacodynamic approaches were performed with use of peripheral
      blood mononuclear cells (PBMCs) from patients with psoriasis. METHODS:
      Cyclosporine effects on PBMC-blastogenesis were examined in 33 patients with
      psoriasis. The drug concentration that gave 50% inhibition of mitogen-stimulated
      PBMC proliferation in vitro (IC50, in nanograms per milliliter) was evaluated in
      each patient. Cyclosporine was administered at an initial dose of 5 mg/kg/day,
      and the dose was tapered for 16 weeks to 3 mg/kg/day. The recovery rate in the
      psoriasis area and the severity index (PASI) 16 weeks after cyclosporine therapy
      began was measured. RESULTS: Cyclosporine IC50 values in 33 patients deviated
      widely, from 0.1 to 120.6 ng/ml. We classified these patients into two groups on
      the basis of their PBMC sensitivity to cyclosporine with use of the median
      cyclosporine IC50 (3.0 ng/ml) of these patients as the cutoff point. The PASI
      recovery rate after cyclosporine therapy in the patients with high sensitivity
      was significantly higher than that in the patients with low sensitivity (p <
      0.0007). Moreover, a significant negative correlation between the IC50 and the
      PASI recovery rate was observed in these 33 patients (r = -0.73; p < 0.0001).
      Blood trough levels and side effects of cyclosporine were not significantly
      different between the two patient groups. CONCLUSIONS: The results showed that we
      could use PBMCs to pharmacodynamically predict the patients with a poor response
      to cyclosporine therapy. These patients may require larger doses of cyclosporine
      or alternative approaches to treatment. The patients with PBMCs sensitive to
      cyclosporine should be evaluated for treatment with smaller doses of the drug to
      avoid serious side effects.

PMID- 9585802
TI  - A dose-response study to assess the renal hemodynamic, vascular, and hormonal
      effects of eprosartan, an angiotensin II AT1-receptor antagonist, in sodium
      replete healthy men.
AB  - STUDY DESIGN: The effects of orally administered eprosartan on changes induced by
      angiotensin II in blood pressure, renal hemodynamics, and aldosterone secretion
      were evaluated in healthy men in this double-blind, randomized, single-dose,
      placebo-controlled crossover study, which was conducted in three parts. Part 1 (n
      = 12) assessed the onset and duration of the effect of eprosartan 350 mg or
      placebo; part 2 (n = 14) assessed the dose-response profile of placebo or 10, 30,
      50, 70, 100 or 200 mg eprosartan; and part 3 (n = 5) assessed the duration of the
      effect of 50, 100, or 350 mg eprosartan. RESULTS: In part 1 of the study; 350 mg
      eprosartan caused complete inhibition of angiotensin II-induced pressor and renal
      blood flow hemodynamic effects (effects on effective renal plasma flow [ERPF])
      and inhibited angiotensin II-induced stimulation of aldosterone secretion from 1
      to 3 hours after administration. Eprosartan, 350 mg, inhibited the effects of
      exogenous angiotensin II by approximately 50% to 70% from 12 to 15 hours after
      dosing. Eprosartan had no angiotensin II agonistic activity and produced an
      increase in ERPF starting at 1 to 4 hours after dosing. In study part 2, at 3
      hours after single doses of 10, 30, 50, 70, 100, and 200 mg, eprosartan inhibited
      angiotensin 11-induced decreases in ERPF by 39.1%, 49.9%, 33.0%, 56.0%, 71.0%,
      and 85.7%, respectively, compared with placebo. In study part 3, 50, 100, and 350
      mg eprosartan produced measurable Inhibition of angiotensin II-induced decreases
      in ERPF from 12 to 15 hours after administration. In parts 2 and 3, the
      eprosartan angiotensin II antagonism on blood pressure response and aldosterone
      secretion mirrored the angiotensin II antagonism on ERPF.

PMID- 9585803
TI  - Artemisinin kinetics and dynamics during oral and rectal treatment of
      uncomplicated malaria.
AB  - OBJECTIVE: To compare parasite clearance times after oral and rectal
      administration of artemisinin in adults with uncomplicated malaria and to relate
      pharmacodynamics with artemisinin kinetics and to disclose any pharmacokinetic
      changes during treatment. METHODS: Thirty male Vietnamese patients with
      falciparum malaria were randomized to treatment with 500 mg artemisinin daily by
      either the oral or rectal route of administration. Parasite densities in
      capillary blood were determined by microscopy every 4 to 6 hours. Artemisinin
      plasma concentrations on the first and last day of treatment were determined by
      HPLC and unbound fractions in plasma were determined by ultrafiltration. RESULTS:
      Mean parasite clearance times and 95% confidence intervals (95% CI) were 25 (95%
      CI, 16 to 33) and 29 (95% CI, 23 to 35) hours during oral and rectal treatment,
      respectively. The bioavailability after rectal relative to oral artemisinin was
      30%. Artemisinin areas under the plasma concentration-time curve (AUC) on the
      fifth (last) day of oral or rectal treatment were 30% (95% CI, 4% to 56%) and 40%
      (95% CI, -6% to 91%), respectively, of those after the first dose. The fraction
      unbound in plasma was 15% (95% CI, 12% to 19%), increasing marginally during
      treatment. No relationship was found between main clinical end points and drug
      exposure, although indices for the rapidity of response onset were lower after
      oral treatment and correlated to unbound AUC values (rS = -0.7; p < 0.001).
      CONCLUSIONS: The similarity in parasite clearance times despite lower drug levels
      during rectal treatment suggests that initial oral doses may be unnecessarily
      high. The singular time dependency of artemisinin pharmacokinetics, attributed to
      autoinduction of drug elimination, has possible implications for combination
      chemotherapy. Decreasing artemisinin concentrations during treatment may partly
      explain recrudescences and increase the risk for resistance development.

PMID- 9585805
TI  - [The value of fluorides in the management of osteoporosis. Munich, 15/16 January
      1998].

PMID- 9585804
TI  - Population pharmacokinetics of sirolimus.

PMID- 9585806
TI  - Alpha interferon treatment in myasthenia gravis: effects on natural killer cell
      activity.
AB  - The efficacy of recombinant interferon-alpha (rIFN alpha), on natural killer (NK)
      cell cytotoxic activity, CD3+, CD4+, CD8+, CD56+, HLA-DR+ lymphocyte counts, anti
      acetylcholine receptor antibody (AChR Ab) levels, single fibre electromyography
      findings (SFEMG) and clinical course were evaluated in patients with myasthenia
      gravis (MG). During the IFN alpha treatment (3 mu, subcutaneous, 3 times a week),
      NK cell cytotoxicity and CD4+/8+ ratio increased, NK cell count remarkably
      decreased, and no significant clinical or SFEMG changes were observed. This
      preliminary open study in MG patients has demonstrated enhanced NK activity per
      unit NK cell after IFN alpha therapy. Although lymphocyte phenotypes and NK
      function approached normal levels during therapy, a higher dose of IFN alpha may
      be required for a significant clinical response. It has been also concluded that
      6 months of IFN alpha therapy seems to be safe in MG, though in patients with
      malignancy, IFN alpha may cause increased autoimmunity, AChR positivity and MG.

PMID- 9585807
TI  - Identification and cloning of a brain autoantigen in neuro-behavioral SLE.
AB  - In murine models of SLE, particular patterns of abnormalities of social
      interaction and memory collectively known as neurobehavioral dysfunction (NBD)
      correlate with the occurrence of brain reactive autoantibodies. Study of the
      immunopathogenic effects of these antibodies has been limited by the absence of
      isolated autoantibodies and antigens. In order to identify the molecular targets,
      we isolated autoantibodies highly specific for brain plasma membranes from
      MRL/lpr mice. After immunoscreening a brain expression library with these brain
      specific autoantibodies, we identified a single cDNA clone of unique sequence and
      relevant anatomic distribution. Transcript for this cDNA is wide spread among
      mammalian species but appears to be present only in the brain. Addition features,
      suggesting this cDNA is pertinent for further study include (1) the expressed
      protein, called lupus brain antigen 1, reacts with the screening immunoglobulins
      as well as immunoglobulins from other strains of murine neuro-SLE not used to
      screen the library, but not with immunoglobulins from normal mice, (2) the
      transcript distribution within the brain is similar to immunochemical
      localization of binding of the spontaneous autoantibodies and (3) the
      localization of transcript within the brain, in the hippocampus, hypothalamus an
      cingulate gyrus, corresponds to anticipated anatomical regions of clinical
      dysfunction. Further, the transcript is a large, potentially structural molecule
      of unique sequence. Antibodies to this molecule may mediate changes in behavior
      either by direct interactions with the cognate antigen or by indirect influences
      through neuro-endocrine axes.

PMID- 9585808
TI  - Substance P C-terminal octapeptide analogues augment tumor necrosis factor-alpha
      release by human blood monocytes and macrophages.
AB  - We have investigated the effects of the substance P C-terminal octapeptide
      analogues [Pro4, Glu (OBzl)11] SP4-11, [Hyp4, Glu(OBzl)11] SP4-11, [cHyp4,
      Glu(OBzl)11] SP4-11 and [kPro4, Glu(OBzl)11] SP4-11 on the constitutive and/or
      lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF-alpha)
      in both freshly isolated human blood monocytes (FIBM) and monocyte-derived
      macrophages (MDM). The cells were treated with substance P and the substance P
      analogues at various concentrations (10-14 to 10-6 M) in the presence or absence
      of LPS and culture supernatants were analyzed for TNF-alpha as measured by an
      enzyme immunosorbent assay (ELISA). Monocytes and macrophages treated with the
      substance P analogues alone increased TNF-alpha secretion at a magnitude similar
      to the effect of entire undecapeptide substance P. The stimulatory effects of the
      substance P analogues on TNF-alpha secretion are inhibited by substance P
      antagonists, spantide ([D-Arg-1-D-Trp-7-D-Trp-9-Leu-11]-SP) and CP-96,345 (a
      nonpeptide antagonist of the substance P receptor), indicating that these effects
      are specific and substance P receptor-mediated. Treatment of monocytes and
      macrophages with the substance P analogues in combination with LPS, however,
      showed no synergistic interaction in upregulation of TNF-alpha. These data
      indicate that the biological effect of substance P on TNF-alpha production by
      human monocytes and macrophages depends mainly on the sequence of the C-terminal
      region of the molecule.

PMID- 9585809
TI  - Interferon-beta-1-b (IFN-B) decreases induced nitric oxide (NO) production by a
      human astrocytoma cell line.
AB  - Inducible nitric oxide synthase (iNOS) is expressed by astrocytes in
      demyelinating regions of multiple sclerosis (MS) brain plaques, suggesting that
      NO contributes to MS pathology. Since the immunosuppressive cytokine IFN-B
      ameliorates MS disease activity, it is of interest to assess the modulatory role
      of IFN-B on NO production. We studied the effects of IFN-B, as well as
      dexamethasone, IL-10, and transforming growth factor-beta (TGF-B), on cytokine
      induced NO production by the human astrocytoma cell line, A172. L-NMMA and
      aminoguanidine, competitive inhibitors of iNOS suppressed NO production as
      measured by the NO byproduct, nitrite, as did IFN-B. Dexamethasone enhanced NO
      production, and IFN-B decreased the amount of the enhancement. Neither IL-10 nor
      TGF-B inhibited nitrite production. The therapeutic effect of IFN-B in MS may be
      partly due to suppression of pathogenic NO production.

PMID- 9585810
TI  - Adrenergic regulation of macrophage-derived tumor necrosis factor-alpha
      generation during a chronic polyarthritis pain model.
AB  - Increases in the levels of proinflammatory cytokines, such as TNF alpha, have
      been intricately linked with arthritis and the pathogenesis of several models of
      neuropathic pain. In addition, arthritis (as well as other types of persistent
      pain) is associated with increased sympathetic activity and alterations of other
      responses in autonomic nervous activity. Adrenergic regulation of LPS-stimulated
      TNF production by M phi isolated from rats with streptococcal-cell-wall (SCW)
      induced arthritis has been examined. Serum TNF levels and the cellular
      composition of peritoneal exudates have also been assessed. M phi were obtained
      from: (1) normal control rats, (2) animals injected with complete Freund's
      adjuvant (CFA), 3 rats injected with SCW and arthritic, and (4) those injected
      with SCW, which failed to develop arthritis. Serum levels of TNF alpha in rats
      that develop arthritis are significantly greater (2.4 fold) than levels from the
      other groups. The proportion of OX19-positive T cell subpopulations are the same
      in peritoneal exudates from all groups. Immunocytochemical staining also reveals
      differences between M phi subgroups in the degree of activation. Peritoneal
      exudates from rats that develop arthritis contain a greater proportion of the
      high TNF producing subclass of M phi, as identified by positive ED3 staining (p <
      0.001). In contrast, Ia antigen presenting M phi (OX6-positive) in the peritoneal
      exudate cells are only elevated in rats administered CFA. The selective blockade
      of adrenergic receptors by idazoxan or propranolol demonstrates that the
      constitutive involvement of either alpha 2 or beta-adrenergic regulation of M phi
      derived TNF production is pronounced in rats with arthritis (p < 0.001). These
      investigations demonstrate a distinctive pattern of peripheral M phi populations
      in rats that develop chronic polyarthritic pain. We believe that identification
      of interactions between the adrenergic responses and proinflammatory cytokines
      will lead to the development of improved strategies to treat patients with
      chronic pain.

PMID- 9585811
TI  - Mechanisms of recovery from experimental autoimmune encephalomyelitis: T cell
      deletion and immune deviation in myelin basic protein T cell receptor transgenic
      mice.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a Th1-type cell-mediated
      autoimmune disease directed against central nervous system (CNS) myelin antigens
      such as myelin basic protein (MBP). EaE is usually characterized by spontaneous
      remission of clinical disease and immune pathology despite the persistence of
      self myelin antigens in the central nervous system. Following induction of an
      acute episode of EAE, spontaneous remission also occurs in MBP T cell receptor
      (TCR) transgenic mice even through most T cells express a TCT specific for MBP.
      To investigate the mechanisms of recovery associated with EAE, we examined the
      behavior of MBP-specific T cells in the MBP TCR transgenic mouse model during
      disease progression and recovery. We found that recovery from EAE was associated
      with three major immunologic changes: (1) deletion of encephalitogenic T cells in
      the brain; (2) deviation of MBP-specific transgenic (Tg+) T cells both in the
      periphery and in the central nervous system from INF- gamma secretin Th1 type
      cells to cells that secrete IL-4, IL-10, and TGF- beta ; and (3) deletion of Tg+
      T cells in the thymus through apoptosis. Thus spontaneous recovery from a classic
      Th1 type organ specific autoimmune disease is associated with two mechanisms of
      immune tolerance, deletion of autoreactive cells and immune deviation of
      autoreactive cells to a non-pathogenic phenotype.

PMID- 9585813
TI  - Interaction between apoptotic cells and reactive brain cells in the central
      nervous system of rats with autoimmune encephalomyelitis.
AB  - To elucidate the role of brain cells in the immune regulation in the central
      nervous system (CNS), acute and chronic relapsing experimental autoimmune
      encephalomyelitis (EAE) was induced in Lewis rats and the location of apoptotic
      inflammatory cells and their interaction with astrocytes and microglia was
      investigated at various stages of the disease. Apoptotic cells detected by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)
      were few in number at day 10-12 post-immunization (PI), increased and peaked at
      day 13 PI. Then, these cells decreased gradually by day 21 PI. The most
      characteristic finding was that apoptotic cells were mainly distributed in the
      CNS parenchyma with only a few cells present in perivascular cuffs. Double
      staining by the TUNEL method and immunocytochemistry for astrocytes and microglia
      revealed that astrocytes were more closely associated with apoptotic cells than
      microglia. Apoptotic cell death may be one mechanism by which T cells are
      eliminated from the CNS. Furthermore, the present study suggests that astrocytes,
      rather than microglia, induce programmed cell death of infiltrating inflammatory
      cells.

PMID- 9585812
TI  - Antibodies to GT1a ganglioside in patients with Guillain-Barre syndrome.
AB  - Serum antibodies from 8 (13%) of 62 patients with the acute Guillain-Barre
      syndrome (GBS) and 1 of 3 patients with the Miller Fisher syndrome (MFS)
      recognized a minor ganglioside in bovine and human brain trisialoganglioside
      fractions. The ganglioside antigen migrated between GD1a and GD1b on thin-layer
      chromatograms. The structure of this ganglioside was established to be GT1a by
      thin-layer chromatography blotting and mass spectrometry. GT1a a ganglioside was
      also detected in human and bovine peripheral nerves by thin-layer chromatogram
      immunostaining. Serum from the GBS patients had IgM, IgG, or IgA antibodies
      against GT1a detectable by enzyme-linked immunosorbent assay (ELISA). Serum from
      the MFS patient also had elevated levels of IG against GT1a. None of the sera
      from 43 patients with other neurological diseases or from 24 healthy controls
      reacted with GT1a. Sera from 6 of 8 GBS patients with anti-Gt1a antibodies also
      reacted with GQ1b. There was no difference in the incidence of anti-GT1a
      immunoglobulins in acute GBS patients with or without oculomotor abnormalities.
      Levels of anti-GT1a antibodies correlated temporally wit clinical symptoms in GBS
      patients. Although the incidence of dysphagia was slightly higher in GBS patients
      with anti-GT1a antibodies than in those without, the number of patients studied
      may have been too small to detect an association between anti-GT1a antibodies and
      an a specific clinical variant of GBS. Our data demonstrate that a proportion of
      GBS patients have antibodies against GT1a ganglioside and suggest that these
      antibodies may play a role in the pathogenesis of neuropathy in GBS.

PMID- 9585814
TI  - Detection of substance P immunoreactivity in human peripheral leukocytes.
AB  - The neuropeptide substance P (SP) has a marked proinflammatory effect and
      modulates the immune response. In this study, we tested the hypothesis that human
      peripheral leukocytes contain SP. Resting peripheral leukocytes collected from
      healthy volunteers (n = 20) were studied by applying a SP rabbit polyclonal
      antiserum to both flow cytometry and immunohistochemistry. To identify possible
      changes in Sp expression, we also analyzed both activated T-lymphocytes (cell
      cultures; n = 5 normal subjects) and neoplastic hematologic samples of different
      types of leukemias. Flow cytometry showed that normal granulocytes and monocytes
      contained SP, whereas lymphocytes were generally negative (or weakly positive)
      with the exception of a few (10-20%) positive subsets. In comparison, activated T
      lymphocytes were markedly immunolabeled by SP as well as samples from neoplastic
      patients demonstrated strong SP immunoreactivity in all cell lineages. This
      pattern was confirmed by immunohistochemistry on cytospins. Our results support a
      potential role for SP-mediated immunomodulatory mechanisms both in normal and
      pathological conditions.

PMID- 9585815
TI  - Diverse patterns of unresponsiveness in an acetylcholine receptor-specific T-cell
      clone from a myasthenia gravis patient after engaging the T-cell receptor with
      three different ligands.
AB  - Using an acetylcholine receptor-specific T-cell clone (TCC) from a myasthenia
      gravis patient, we have compared the induction of unresponsiveness by three
      agents: an anti-V beta monoclonal antibody (mAb), complexes of MHC class II with
      specific peptide (DR4:peptide) and free peptide. Pretreatment with each agent
      without antigen-presenting cells specifically rendered the TCC unresponsive to a
      subsequent optimal stimulus. A substantial proportion of the DR4:peptide
      pretreated cells underwent apoptosis and the remainder were profoundly
      unresponsive. Apoptosis was less prominent after pretreatment with free peptide
      and was not significant with anti-V beta mab; with both, the unresponsiveness was
      transient in the survivors. These diverse effects of engaging the T-cell receptor
      in the absence of costimulation suggest that these agents act via different
      mechanisms, and give insights to the potential for specific immunotherapy.

PMID- 9585816
TI  - Differential effects of stress-induced adrenal function on components of the
      herpes simplex virus-specific memory cytotoxic T-lymphocyte response.
AB  - We have previously demonstrated in a murine model system that psychological
      stress, applied in the form of physical restraint, suppresses both the activation
      of splenic-derived, herpes simplex virus (HSV)-specific memory cytotoxic T
      lymphocytes (CTLm) to the lytic phenotype and the production of cytokines
      associated with CTL activation and function. In the studies described herein, we
      investigated the hypothesis that an adrenal-dependent event is responsible,
      either in whole or in part, for these observations. While adrenalectomy was shown
      to abrogate stress-induced suppression of both HSV-specific CTLm activation and
      the production of IL-6 and IFN-gamma, the reduction in splenic cellularity
      associated with restraint stress remained, In addition, a role for adrenal
      function in the regulation of splenic cellularity and IFN-gamma production in non
      stressed mice was observed. Together, these results indicate that both adrenal
      dependent and adrenal-independent events, operative under both baseline and
      stress conditions, mediate control of the memory component of the cellular immune
      response to HSV infection. Overall, these studies provide insight into the
      mechanisms by which psychological stress modulates immune responsiveness to viral
      pathogens.

PMID- 9585817
TI  - Selection of recombinant anti-HuD Fab fragments from a phage display antibody
      library of a lung cancer patient with paraneoplastic encephalomyelitis.
AB  - Antibodies against the HuD antigen expressed in small-cell lung cancer (SCLC)
      cross-react with proteins expressed in neurons of the central and peripheral
      nervous system and are associated with paraneoplastic encephalomyelitis and
      sensory neuropathy (PEM/SN). We isolated anti-HuD Fab fragments from an antibody
      phage display library that was constructed from mRNA of a metastatic lymph node
      from a patient with SCLC and Pem/SN. Fab GLN495 recognized HuD and other related
      proteins (HuC and Hel-N1, or Hu antigens) in immunoblots of these recombinant
      proteins and in immunohistochemical and Western blot analysis of SCLC and
      neurons. Fab GLN495 inhibited up to 75% of the anti-Hu antibodies of the patient
      from which it was derived, suggesting that recognizes a dominant epitope in the
      polyclonal anti-Hu antibody response. Fab GLN495 also competed with anti-Hu sera
      from most but not all patients with PEM/SN, indicating that the same epitope is
      recognized by a large subgroup of patients. Human monoclonal anti-HuD antibodies
      may be useful in diagnosis of HuD expressing tumors and in clarifying the
      autoimmune etiology of PEM/SN. This study, the first to demonstrate that tumor
      specific recombinant antibodies can be isolated from metastatic lymph node
      tissue, shows that this approach may be generally applicable to isolate human
      antibodies against tumor specific antigens.

PMID- 9585818
TI  - Optic neuritis in chronic relapsing experimental allergic encephalomyelitis in
      Biozzi ABH mice: demyelination and fast axonal transport changes in disease.
AB  - The encephalitogenicity of optic nerve tissue was demonstrated in Biozzi ABH (H
      2(dq1)) mice. Acute experimental allergic encephalomyelitis (EAE) occurred in
      11/14 animals and 4/5 exhibited relapse. The involvement of the optic nerve in
      spinal cord homogenate induced chronic relapsing EAE (CREAE) was demonstrated by
      mononuclear cell infiltration and myelin degradation in the optic nerve prior to
      and during clinical disease. During the relapse phase gross pathological
      assessment revealed swollen and translucent plaques on the optic nerves. Advanced
      lesions showed widespread demyelination, astrocytic gliosis and fibrotic changes
      of the blood vessels. Physiologically, the fast axonal transport of proteins from
      the retina to the optic nerve and superior colliculus was significantly decreased
      during relapse. The association of inflammation and demyelination with
      physiological deficit in the optic nerve highlights the usefulness of this model
      in the study of multiple sclerosis in which acute monosymptomatic unilateral
      optic neuritis is a common manifestation. Furthermore, the novel induction of
      CREAE with optic nerve homogenate suggests that optic neuritis is a common
      significant role in the pathophysiology and progression of neurological disease
      in CREAE which may be relevant to studies of optic neuritis in multiple
      sclerosis.

PMID- 9585819
TI  - Treatment of agitation in older persons with dementia. The Expert Concensus Panel
      for agitation in dementia.

PMID- 9585820
TI  - Betting on immunotherapy.

PMID- 9585821
TI  - Home environment and asthma in school children from the Edirne region in Turkey.
AB  - Studies have shown that environmental factors contribute to the development of
      asthma. Hence, we investigated the relation between current asthma and indoor
      environmental factors such as exposure to pets, tobacco smoke, home dampness,
      number of people living in home, and stuffed toys in child's bedroom in a
      questionnaire based study in primary school children aged 6 to 12 years living in
      Edirne (Turkey). In a random sample of 4 primary schools, questionnaires were
      completed by parents of 1000 children. Following the evaluation of 682 of these,
      85 were selected as cases of asthma of which 24 were diagnosed by a physician.
      When required certain laboratory tests were also performed in order to confirm
      the diagnosis. Logistic regression was used to investigate the associations
      between asthma and potential risk factors. In logistic regression analyses, the
      following factors were associated with asthma. Dampness in the house [(odd's
      ratio (O.R) = 2.61; 95% CI 1.13 to 6.81), stuffed toys in the child's bedroom
      (O.R = 2.18; 95% CI 1.27 to 3.74), and the crowding index (O.R = 2.73; 95% CI
      1.08 to 6.82)]. In conclusion, it was found that presence of asthma was
      significantly associated with the presence of dampness in the house, and stuffed
      toys in the child's bedroom. Asthma can be prevented by improvement of the indoor
      environment. Therefore providing education to high-risk populations for avoidance
      of these risk factors is particularly important.

PMID- 9585822
TI  - [Investigation of the efficacy and tolerability of azelastine nasal spray versus
      ebastine tablets in patients with seasonal allergic rhinitis].
AB  - The efficacy and safety of the nasally administered histamine H1 receptor
      blocking drug Azelastine was investigated in an open, multicenter, randomized
      comparative trial with Ebastine in seasonal allergic rhinitis. 110 patients in
      two parallel groups were treated for 14 days and efficacy was assessed by the
      physician using a rating scale measuring 10 nasal and ocular symptoms of seasonal
      rhinitis (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Tolerability was
      measured on the basis of reported adverse events. Both treatment groups had
      dramatic reductions in the physician's total symptom score following treatment (p
      < 0.0005). There was no significant difference between the two groups. Changes in
      individual rhinitis symptoms showed no differences between the two groups. During
      treatment, 19 patients had at least one adverse event, 13 in Azelastine group and
      6 in Ebastine group; all were mild. The most frequent adverse events reported
      were somnolence (4 cases in Ebastine group) and a bitter taste (4 patients in the
      Azelastine group). In conclusion, the results of the study on 110 patients
      suggest that both Azelastine and Ebastine are effective treatments of the
      symptoms of seasonal allergic rhinitis. Both drugs were well tolerated.

PMID- 9585823
TI  - [Safety and efficacy of OM-85-BV plus amoxicillin/clavulanate in the treatment of
      subacute sinusitis and the prevention of recurrent infections in children].
AB  - A 6-month double-blind, prospective, randomized, placebo-controlled trial was
      conducted to establish the safety and efficacy of OM-85-BV in the treatment of
      subacute sinusitis and in the following prevention of the respiratory tract
      infections in 56 children from 18 months to 9 years of age. In the subacute phase
      of the sinusitis the patients were given one OM-85-BV capsule (3.5 mg of
      bacterial extracts) (n = 26) or placebo (n = 30), daily for ten days;
      additionally both groups took amoxicillin/clavulanate 40/10 mg/kg daily in three
      divided doses for 21 days. For the following two months the patients took one OM
      85-BV capsule or placebo, ten days a month. In the subacute phase the OM-85-BV
      group of patients improved sooner (5.56 +/- 4.98 vs 10 +/- 8.49 days) and had a
      shorter convalescence (15.38 +/- 8.91 vs 20.28 +/- 7.17 days). During the six
      month follow-up the patients in the OM-85-BV group had a lower number of
      infections (1.56 +/- 0.3 vs 2.22 +/- 0.43) and required a lower number of drug
      treatments (1.47 +/- 0.32 vs 1.94 +/- 0.42). One patient treated with OM-85-BV
      presented a mild rash which disappeared three days after the drug
      discontinuation. We conclude that OM-85-BV is safe at pediatric ages, as well as
      accelerates the cure and improvement of subacute sinusitis while it lowers the
      incidence of respiratory infections.

PMID- 9585824
TI  - Acute IgE-mediated generalized urticaria-angioedema after topical application of
      povidone-iodine.
AB  - Povidone is a synthetic polymer mainly used as a dispersing or suspending agent
      for many pharmaceutical products. It is also used as a carrier for iodine. In
      many countries it is not mandatory its inclusion in drug labels so many adverse
      effects may be under diagnosed. Povidone-iodine used as a topical antiseptic
      solution may produce allergic contact dermatitis and irritation. Povidone, when
      systemically administered may deposit in tissues causing local lesions and pain.
      Three cases of immediate hypersensitivity to this agent have been reported. We
      present a patient who developed generalized urticaria and angioedema immediately
      after the first topical use of Betadine (povidone-iodine) on a right arm wound.
      The positive skin prick test to Betadine and povidone extract and the
      demonstration of serum specific IgE to povidone, confirmed an IgE-mediated
      hypersensitivity.

PMID- 9585826
TI  - [Clinical investigation. Science or art?].

PMID- 9585825
TI  - Novel approaches to immunotherapy: epitopes, determinants, activators, or
      modulators?
AB  - The immunological mechanism through which immunotherapy (IT) acts is not
      certainly known. The participation of the so-called "blocking antibodies" has not
      been proved and how it intervenes in the regulation of the production of IgE is
      still to be cleared, as it affects the action of lymphocytes Th1 and Th2.
      Nowadays, IT is based in the concept that the allergic reaction is somehow an
      antigen (allergen)-antibody (reagin) reaction. The possible modifications of IT
      are also based on the possibility to interfere in the antigen-antibody
      interaction. It has been proved in vitro that aqueous extracts of some allergens
      produce the consumption of complement, by its usual via, in which the C1
      component is involved, without the mediation of antibodies, generating
      anaphylotoxin C3a, which is a powerful releaser of histamine, as well as C3b,
      which participates in the regulation of the cellular immunitary system. The term
      atopen should therefore be used when referring to the unspecific activation or
      adjuvant activity of antigenically different allergens, due to their common
      structural or functional characteristics. The term allergen should then be used
      when describing those structural traits of the carrier molecule, which
      preferently produces the induction, and possible recognition of IgE antibodies.
      The action atopen and allergen as separate characteristics of a same molecule
      could theoretically become important in the future of therapeutics. The receptor
      of membrane CD21 for C3b, in B cells is a link for lectine CD23 of lymphocytes B,
      which has been identified with the low affinity receptor IgE (Fce RII-CD23). In
      summary, the basic defect in atopy may reside in a defect of the receptor portion
      of reagin for atopen, but not in IgE. This means that in the nearby future, this
      fact should be taken into account in the search of drugs which participate in
      this kind of activation of allergic reaction, trying to modify or modulate the
      low affinity receptor IgE or even the high affinity receptor IgE.

PMID- 9585827
TI  - IgG antibodies to chlamydial and mycoplasma infection plus C-reactive protein
      related to poor outcome in unstable angina.
AB  - OBJECTIVES: Evidence exists showing an association between Chlamydial infection
      and infarction. Our purpose was to identify an interactive relationship between
      Chlamydia pneumoniae and unstable angina. METHODS: We analyzed IgG antibodies for
      Chlamydia pneumoniae, Mycoplasma pneumoniae, and C reactive protein in patients
      during the acute phase of unstable angina. RESULTS: Chlamydia antibodies were
      present in 16.92% (11 cases) of the unstable angina patients. They were also
      present in 34.61% of those patients who experienced ischemic events vs 5.1% who
      did not (odds ratio 9.79, 95% CL 1.65 to 75.26, p = 0.002). Mycoplasma pneumoniae
      antibodies were present in 12.30% of patients but did not emerge as a predictive
      variable. C-reactive protein was present in 22 cases (33.84%), 9 of which were
      associated with recurrent events (34.61%) vs 13 which were free of them (odds
      ratio, p = 0.5). The interactive relationship between infection plus C-reactive
      protein achieved a statistical significant association with ischemic events (odds
      ratio 14, 95% CI 1.49-331.1; p = 0.003). CONCLUSIONS: These findings suggest a
      pathophysiologically based relationship between infective and inflammatory
      processes related to poor clinical outcome during the in-hospital stay in the
      setting of unstable angina patients.

PMID- 9585828
TI  - [Epidemiologic profile of transtelephonic electrocardiography in El Salvador
      during 1994].
AB  - A total of 3,787 electrocardiograms were obtained with transtelephonic monitors
      (TT-ECG) during 1994 in CardioTel of Central America, Nueva San Salvador, El
      Salvador. Each case was evaluated in terms of patient's risk and classified as
      high or low risk on basis of its clinical profile. There were 3,441 traces of low
      risk patients and 346 of high risk one. Female patients accounts for 64.7% of
      cases, with 35.3% corresponding to males. Of all the TT-ECG's a 52.3% were
      normal. Subjects older than 60 years (independently of risk had a greater
      probability of an abnormal TT-ECG; in the same way there was an statistically
      significative increase in the incidence of abnormal TT-ECG in high risk subjects
      compared with low risk ones. In respect to specific TT-ECG abnormalities against
      cardiovascular risk, a high risk condition implied a greater incidence of bundle
      branch blocks, signs of myocardial lesion/necrosis, left ventricular hypertrophy,
      sinus tachycardia and bradycardia, atrial fibrillation and premature ventricular
      and supraventricular complexes, with a p value of 0.05 of 0.001. CONCLUSIONS: TT
      ECG is useful in the search of cardiovascular disease, regardless the presence or
      absence of symptoms. Age greater than 60 years and high cardiovascular risk
      implies a greater probability of abnormal TT-ECG.

PMID- 9585829
TI  - [Radiofrequency ablation of accessory pathways in the presence of atrial
      fibrillation].
AB  - Radiofrequency catheter ablation was performed in 595 consecutive patients with
      Wolff-Parkinson-White syndrome. We attempted ablation of right and left accessory
      pathways, during sustained atrial fibrillation with rapid anterograde conduction
      over the accessory pathway in three patients. In other patient, who had an
      accessory pathway with anterograde decremental conduction properties, referred to
      as Mahaim atriofascicular fiber, originating from the right posterolateral
      atrium, who also had sustained atrial fibrillation during the
      electrophysiological study to assess accessory pathway conduction properties, was
      also submitted to ablation of the accessory pathway. At the successful ablation
      sites, a ventricular electrogram was consistently recorded preceding the onset of
      preexcitation, in the surface electrogram by 20 ms, during atrial fibrillation.
      All patients were successfully ablated with a single radiofrequency impulse.
      After successful ablation direct current cardioversion with 200 joules terminated
      the atrial fibrillation. In conclusion, radiofrequency catheter ablation of
      accessory pathways during sustained atrial fibrillation is feasible with a high
      success rate.

PMID- 9585830
TI  - [Myocardial ischemia secondary to coronary fistula of the anterior descending
      artery with drainage into the pulmonary artery].
AB  - This article reports the clinical and angiographic aspects of three patients with
      congenital coronary arteriovenous fistula to the main pulmonary artery, which
      manifested as dyspnea crisis and angina. This three cases were found in the
      course of 4,400 consecutive cardiac catheterization procedures to study coronary
      artery disease. The interest of the cases reported is based on the peculiar
      anatomy of the fistula. Prompt diagnosis is relevant for better prognosis and
      treatment.

PMID- 9585831
TI  - [Late potentials and variability of cardiac frequency in chronic chagasic
      myocardiopathy and other myocardiopathies].
AB  - In patients suffering dilated cardiomyopathy, chagasic or not, and in healthy
      volunteers we applied signal-averaged electrocardiography to detect late
      potentials and to study heart autonomic control. Thus, with non-invasive methods,
      we were able to explore the progress of depolarization and heart rate
      variability. It was found that Chagasic patients have more late potentials and
      abnormalities in the heart variability; with less co-morbid process when compared
      with patients suffering miscellaneous cardiomyopathies. These preliminary
      findings corroborate and expand previous observations by several authors. The
      signal-averaged electrocardiogram is a valuable tool for clinical diagnosis and
      research, particularly for studies on dilated cardiomyopathy, specially those
      with parasitic etiology.

PMID- 9585832
TI  - [Struma cordis: first case in Mexico].
AB  - The Intracardiac ectopic thyroid is an extremely rare condition and there is no
      previous report on this subject in Mexico. This is the case of a 33 years old
      woman, with normal thyroid function. She was found to have an intracardiac tumor
      in the interventricular septum. The intraoperative biopsy showed typical thyroid
      follicules; tumor removal left a septal defect that was closed with a dacron
      patch suture. Two years follow-up showed normal echocardiographic images, good
      clinical status an normal thyroid functioning. A brief review of the literature
      is included.

PMID- 9585833
TI  - [Persistent atrial paralysis: reported of 2 cases].
AB  - Persistent atrial standstill is an uncommon clinical finding, this condition has
      no atrial electrical activity and do not respond to electrical stimulation.
      Electrophysiologic mapping of the heart, demonstrates two types of standstill:
      total and partial. There are three types of patients with this condition:
      patients with chronic cardiopathy, patients with muscular dystrophy and the third
      idiopathic group. In this article, we present two clinical cases, the fist one
      with dilated cardiomiopathy, in which we demonstrated total atrial standstill.
      The second patient with rheumatic heart disease, in which we demonstrated partial
      standstill that included the apical portion of the rigth atrium. We discuss the
      clinical and electrophysiological finding of both cases and we review the
      literature.

PMID- 9585834
TI  - Complex angioplasty and stenting of a saphenous bypass graft using the
      percutaneous radial approach. Report of a case.
AB  - A severely diseased aortocoronary venous by-pass graft is reported. A successful
      angioplasty plus stenting was performed, via right radial artery, without using a
      guiding-catheter.

PMID- 9585835
TI  - [Is the vectorcardiogram useful in clinic?].

PMID- 9585836
TI  - [Evolution of the knowledge about platelets].

PMID- 9585837
TI  - Medical conditions, medications, and driving.

PMID- 9585838
TI  - Family practice maternity care.

PMID- 9585839
TI  - From outer space to inner space. Neuroscience research aboard the space shuttle.

PMID- 9585840
TI  - Never the same again. Family doctors' priorities challenged by ice storm.

PMID- 9585842
TI  - Assessment needs more emphasis.

PMID- 9585841
TI  - Caring for America's poor.

PMID- 9585843
TI  - Managing exposure to chickenpox during pregnancy. New program.
AB  - QUESTION: Every year several of my pregnant patients ask me what to do about
      being exposed to a child who later comes down with chickenpox. What is your
      recommendation? ANSWER: Whether or not a mother had chickenpox in childhood often
      does not accurately determine her immunity. A rapid test, such as the latex
      agglutination test, is useful. If test results are negative, or if testing is not
      feasible, varicella zoster immunoglobulin should be administered within 96 hours
      of exposure.

PMID- 9585844
TI  - Ophthaproblem. Thyroid-related eye disease.

PMID- 9585845
TI  - Radiology rounds. Round pneumonia.

PMID- 9585846
TI  - Dermacase. Digital mucous cyst.

PMID- 9585847
TI  - Practice tips. Easier shave excision.

PMID- 9585848
TI  - Does ranitidine work for gastroesophageal symptoms during pregnancy?

PMID- 9585849
TI  - Is sertraline an effective therapy for premenstrual dysphoric disorder?

PMID- 9585850
TI  - Are drivers with CVD more at risk for motor vehicle crashes? Study of men aged 45
      to 70.
AB  - OBJECTIVE: To examine whether male drivers aged 45 to 70 years suffering from
      cardiovascular disease (CVD) are more likely to be involved in motor vehicle
      crashes (MVC) that are reported to the police. DESIGN: Population-based case
      control study. SETTING: Data on drivers' ages and medical conditions were
      compiled from the Societe de l'assurance automobile du Quebec's (SAAQ)
      computerized files. A questionnaire was mailed to all subjects to collect
      additional information on annual distances driven and various driving behaviours.
      PARTICIPANTS: Age-stratified population-based random sample. Subjects were 2504
      drivers involved in MVCs during a 6-month period; controls were 2520 drivers not
      involved in crashes. MAIN OUTCOME MEASURES: Proportion of drivers with CVD
      involved in MVCs. RESULTS: Response rate to the questionnaire was 35.5%. Analysis
      of the SAAQ files' entire sample of 5024 drivers showed that drivers suffering
      from CVD were less likely to be involved in MVCs (odds ratio [OR] 0.82, 95%
      confidence interval [CI] 0.67 to 0.99) than drivers without CVD. Although the
      estimate of risk remains unchanged when adjusted for age, it becomes
      statistically insignificant. It also remains unchanged and statistically
      insignificant when adjusted for yearly distance driven and driver behaviour, as
      shown by responses to the questionnaire. Drivers suffering from CVD drove
      significantly less each year (8900 km) than drivers without medical conditions
      (13,000 km). CONCLUSION: This study shows no increased risk of motor vehicle
      crashes for drivers suffering from CVD.

PMID- 9585851
TI  - Cardiovascular disease. Physician attitudes toward prevention and treatment.
AB  - OBJECTIVE: Survey of physician attitudes toward practising cardiovascular disease
      prevention. DESIGN: Questionnaire administered via telecommunication from 1992
      through 1994. SETTING: The FAMUS (Family Medicine, University of Sherbrooke)
      project, between 1992 and 1996, used weekly telecommunication to collect data
      from 200 general practitioners throughout the province of Quebec on
      cardiovascular disease risk factors and their treatment. PARTICIPANTS: Of 200
      physicians contributing to the FAMUS project, 156 completed questionnaires
      (response rate 78%). MAIN OUTCOME MEASURES: Variations in attitudes to prevention
      policy and risk factor interventions. RESULTS: Survey results revealed physicians
      knew important risk factors for cardiovascular disease but differed in attitudes
      toward efficacy of treatment. Intervention to control cholesterol was thought to
      be very effective by 21.2% (95% confidence interval [CI] 21.2 +/- 6.4) and
      without effect by 10.3% (95% CI 10.3 +/- 4.8). Intervention to improve dietary
      habits was considered ineffective by 48.1% (95% CI 48.1 +/- 7.8). Confidence in
      managing risk factors varied; most respondents described themselves as only
      moderately skilled. A few practitioners (30.1%; 95% CI 30.1 +/- 7.2) acknowledged
      practice guidelines as an important source of information on which to base
      preventive interventions. Only 14.7% (95% CI 14.7 +/- 5.6) of those surveyed
      included remuneration as contributing to their implementation of prevention
      activities in practice. CONCLUSIONS: Variations in physician attitudes could
      influence risk factor intervention. Interventions to change lifestyle are
      associated with uncertainty about patient compliance, efficacy of treatment, and
      ability to effect lifestyle changes.

PMID- 9585852
TI  - Admissions and transfers from a rural emergency department.
AB  - OBJECTIVE: To examine the characteristics of patients transferred from a rural
      hospital emergency department, to compare them with patients admitted on an
      emergency basis, and to use this information to help plan physician education.
      DESIGN: Descriptive study using records for the period January 1, 1991, to June
      30, 1992. SETTING: The emergency department at Bonnyville Health Centre, an acute
      care rural hospital located 240 km northeast of Edmonton, serving a catchment
      population of approximately 10,000. PARTICIPANTS: One thousand fifty-five
      patients seen in the emergency department who were either transferred to another
      centre or admitted to the Bonnyville Health Centre on an emergency basis. MAIN
      OUTCOME MEASURES: For the transferred group, main diagnosis, category of
      transfer, and reason for transfer. For the admitted group, main diagnosis, length
      of stay, type of discharge. RESULTS: Of the 1055 patients ill enough to be either
      admitted or transferred, 114 (10.8%) were transferred. Those transferred were
      predominantly men, the elderly, and people with orthopedic injuries or neurologic
      diseases. Those admitted presented primarily with internal, respiratory,
      gynecologic, or pediatric disorders. Reason for transfer was mainly lack of
      specialized services or equipment at the rural hospital. CONCLUSIONS: Patients
      transferred out of the emergency department differed from those admitted in
      diagnoses and sex. Most transfers were considered "mandatory." Results of this
      analysis supported incorporating a formal rotation in orthopedics and adding 4
      weeks to the existing emergency medicine rotation in our family medicine
      residency program.

PMID- 9585854
TI  - [Diogenes' syndrome. A geriatric entity].
AB  - OBJECTIVES: To familiarize physicians with this relatively rare syndrome; to
      review the signs and symptoms, with special emphasis on its nature and the
      terminology used; and to help physicians choose an appropriate course of action.
      DATA SOURCES: MEDLINE (1966 to 1997) and Psychlit (1990 to 1996), references from
      articles, reference texts on geriatrics and psychiatry. STUDY SELECTION: All of
      the articles reviewed involved case studies. SYNTHESIS: Descriptive articles
      enabled us to define this syndrome more clearly. The dissimilarity of the case
      studies indicates that the condition is not clearly defined, and the reference to
      the Greek philosopher Diogenes is misleading. CONCLUSION: The various features
      described to make up a geriatric syndrome characterized by extreme self-neglect,
      squalid living conditions, and social withdrawal. This complex geriatric problem
      poses clinical, social and ethical challenges.

PMID- 9585853
TI  - Benzodiazepine use and motor vehicle accidents. Systematic review of reported
      association.
AB  - OBJECTIVE: To examine the relationship between benzodiazepine (BZD) use and motor
      vehicle accidents (MVAs). DATA SOURCES: MEDLINE was searched from 1980 to 1997
      using the key words traffic accidents or motor vehicle accidents and
      benzodiazepines (and alternative terms and outcomes) in English, German, French,
      or Italian. STUDY SELECTION: Case-control studies of BZDs and MVAs; police or
      emergency studies of BZD use among travelers; driving tests with subjects taking
      BZDs. Outcomes were impaired driving, accidents; mortality; postaccident medical
      attention, emergency ward care, or hospitalization. Quality criteria were whether
      all driving BZD users and non-users had an equal chance of entering the study;
      whether medication dosage and timing were ascertained; whether all kilometres
      driven by BZD users and non-users were studied; whether all types of accidents
      were ascertained; and whether medical conditions were controlled for. SYNTHESIS:
      In case-control studies, the odds ratios for mortality and emergency medical
      treatment ranged from 1.45 to 2.4 in relation to time of use and quantity of drug
      taken. In police and emergency ward studies, BZD use was a factor in 1% to 65% of
      accidents (usually 5% to 10%). In two studies where subjects had blood alcohol
      concentrations less than the legal limit, BZDs were found in 43% and 65% of
      subjects. In one study with controls, 5% of drivers and 2% of controls in
      accidents had used BZDs. CONCLUSIONS: Case-control studies suggest using BZDs
      approximately doubles the risk of motor vehicle accidents. The risk for drivers
      older than 65 of being involved in reported motor vehicle collisions is higher
      when they take longer-acting and larger quantities of BZDs.

PMID- 9585855
TI  - Developing and supporting school health programs. Role for family physicians.
AB  - PROBLEM BEING ADDRESSED: School staff are anxious about the demands on their time
      associated with a perceived increase in health problems among their students.
      OBJECTIVE OF PROGRAM: To respond to these concerns by developing a health
      committee in two elementary schools and one high school. The health committee
      could perform needs assessments and, with the results of these assessments and a
      careful literature review, could develop health policies and procedures
      appropriate to the school environment and to evolving community expectations.
      MAIN COMPONENTS OF PROGRAM: A committee of four family physicians (nonremunerated
      parents of students), one of whom served as Chair, four school administrators,
      and one part-time remunerated nurse practitioner explored aspects of illness in
      the schools. They studied approaches to acute and chronic student illness;
      emergency response; management of children with special needs; environmental
      safety; health promotion; and the availability and quality of resources for
      learning about health for teachers, administrators, parents, and students.
      CONCLUSION: Opportunities exist for family physicians to expand their involvement
      in child and adolescent health in schools. Involvement should be collaborative
      and multidisciplinary and reflect community interests and needs.

PMID- 9585856
TI  - Rural obstetrics. Joint position paper on rural maternity care. Joint Working
      Group of the Society of Rural Physicians of Canada (SRPC), The Maternity Care
      Committee of the College of Family Physicians of Canada (CFPC), and the Society
      of Obstetricians and Gynaecologists of Canada (SOGC).

PMID- 9585857
TI  - Health Canada to launch physical activity guide.

PMID- 9585858
TI  - Hotel de Health. Traveler's Caribbean dialysis resort.

PMID- 9585859
TI  - The future role of anti-tumour necrosis factor (TNF) products in the treatment of
      rheumatoid arthritis.
AB  - Tumour necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine which is
      overproduced in rheumatoid joints primarily by macrophages. This cytokine has a
      potential pathogenic role in the establishment of rheumatoid synovitis, in the
      formation of pannus tissue and in the process of joint destruction, as it
      increases synoviocyte proliferation and triggers a cascade of secondary mediators
      involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the
      process of joint destruction. These findings made TNF alpha a potential target
      for anticytokine therapy. Experimental studies have shown that TNF alpha blockade
      by monoclonal antibodies or by soluble TNF receptor reduced the extent and
      severity of arthritis both in collagen-induced arthritis in mice and in
      transgenic mice overexpressing TNF alpha, which develop a rheumatoid-like
      destructive arthritis. Clinical studies based on the use of anti-TNF alpha
      antibodies or soluble receptors have suggested a potential beneficial effect of
      TNF alpha-blocking therapy in inducing amelioration of inflammatory parameters in
      patients with long-standing active disease. In these patients anti-TNF alpha
      therapy induces a rapid improvement in multiple clinical assessment of disease
      activity, including morning stiffness, pain score, Ritchie articular index and
      swollen joint count. The clinical benefits are associated with an improvement in
      some serological parameters, such as C-reactive protein and serum amyloid-A,
      erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells
      and platelet counts, rheumatoid factor titre and histological features of the
      synovium. However, it remains to be determined whether anti-TNF alpha therapy may
      be useful in the long term management of rheumatoid patients and in the
      achievement of better outcomes of disease. Because TNF alpha production also
      serves a specific function in host defence against infections and tumours, the
      adverse effects of long term anti-TNF alpha therapy must be carefully evaluated.
      In addition, targeting a single mediator may be not sufficient to block the
      complex inflammatory response in rheumatoid arthritis. For these reasons
      therapeutic strategies aimed at concomitantly interfering with multiple
      pathogenic pathways are currently under investigation.

PMID- 9585860
TI  - Colloid volume expanders. Problems, pitfalls and possibilities.
AB  - Colloid solutions have been developed and used over the past 70 years as
      expanders of the intravascular space, based on an understanding of Starling's
      law. Increasing osmotic pressure with colloidal products has remained an
      attractive theoretical premise for volume resuscitation. Indeed, colloids have
      been shown to increase osmotic pressure in clinical practice; however, the
      effects are short-lived. Lower molecular weight colloids exert a larger initial
      osmotic effect, but are rapidly cleared from the circulation. Larger molecules
      exert a smaller osmotic pressure that is sustained longer. The main drawback to
      colloid therapy lies in pathological states with endothelial injury and capillary
      leak, precisely the clinical scenario where colloids are commonly given. The
      colloid solution may leak into the interstitium and remain there exerting an
      osmotic gradient, pulling additional water into the interstitium. There are 4
      general types of colloid products available for clinical use. Albumin is the
      predominant plasma protein and remains the standard against which other colloids
      are compared. Albumin, pooled from human donors, is in short supply and remains
      expensive. Dextrans have been used to prevent deep venous thrombosis and to lower
      blood viscosity during surgery. Hetastarch has been widely used as a plasma
      volume expander. It provides equivalent plasma volume expansion to albumin, but
      has been shown to alter clotting parameters in studies (prolonging the activated
      partial thromboplastin time and prothrombin time). Although severe coagulopathies
      have been reported in sporadic cases, hetastarch has not been shown to increase
      postoperative bleeding compared with albumin therapy, even in large doses (3
      L/day). Despite some theoretical advantages compared with crystalloid therapy,
      colloid administration has not been shown to decrease the risk of acute lung
      injury or to improve survival. Specific indications for colloid products include
      hypoproteinaemic or malnourished states, patients who require plasma volume
      expansion who are unable to tolerate larger amounts of fluid, orthopaedic and
      reconstructive procedures requiring prevention of thrombus formation and
      leukapheresis.

PMID- 9585861
TI  - Chronotherapeutics for cardiovascular disease.
AB  - Chronotherapeutics, or delivery of a medication in concentrations that vary
      according to physiological need at different times during the dosage period, is a
      relatively new practice in clinical medicine. Epidemiological studies document
      that the incidence of many cardiovascular diseases, including myocardial
      infarction and stroke, varies predictably in time over 24 hours (the circadian
      period). Advanced diagnostic technologies using ambulatory monitoring of the
      blood pressure and electrocardiogram have also demonstrated that there is marked
      variability in the level of pressure in hypertensive patients and the degree of
      myocardial ischaemia in patients with coronary disease. These diagnostic
      techniques also allow us to study the effects of varying the timing of
      administration or delivery of a concentration of a drug on end-points such as
      changes in blood pressure, heart rate or intensity of angina. The first
      chronotherapeutic agent for hypertension and angina pectoris, controlled onset,
      extended release (COER-24) verapamil, has recently been developed and registered
      in the US, Brazil, Canada and Mexico. The theoretical advantage of this
      formulation is that delivery of the active drug, verapamil, has been tailored to
      the typical circadian rhythm of blood pressure and heart rate in patients with
      hypertension and angina to better cover the early morning hours when
      cardiovascular need appears to be the greatest. An outcome study (CONVINCE) that
      evaluates primary prevention of cardiovascular events with this chronotherapy
      versus standard of care therapy is under way in several countries in North and
      South America and Europe.

PMID- 9585864
TI  - Guidelines to reducing delays in administration of thrombolytic therapy in acute
      myocardial infarction.
AB  - The thrombotic coronary accident that triggers a myocardial infarction initiates
      a 'wavefront' of ischaemic cell death that can be aborted by timely restoration
      of blood flow. Myocardium destined for necrosis can be salvaged by quick lysis of
      the culprit clot to restore perfusion, reduce infarct size and save lives. While
      a number of useful thrombolytic regimens have been investigated, the greatest
      barrier to optimising efficacy is reducing the delay between the onset of
      symptoms and administration of thrombolytic therapy. Clinical experience has
      confirmed laboratory evidence that prompt restoration of coronary blood flow can
      salvage more than 50% of ischaemic myocardium if achieved within 2 hours.
      However, after 6 hours of sustained ischaemia, the opportunity to achieve
      meaningful salvage is largely lost. Analysis of pooled data estimates that for
      each hour of delay 1.6 fewer lives are saved per 1000 patients treated. Other
      investigators have estimated 60 to 80 lives saved per 1000 patients treated
      within 1 hour of symptom onset. More realistically, the time from symptom onset
      to treatment averages 2.5 to 5 hours in various studies. Reluctance to seek
      medical help results in a delay of more than 4 hours in at least 40% of patients.
      There may be some benefits of late, time-independent reperfusion from 12 to 24
      hours after symptoms. Some hibernating myocardium may be salvaged resulting in
      less adverse late ventricular remodelling, reduced infarction expansion and
      improved electrical stability. Barriers to timely thrombolytic treatment may be
      classified as presentation delay or treatment delay. Strategies to optimise
      timely treatment have included pre-hospital administration of thrombolytics. This
      achieves greatest benefit when used in a more rural setting where transportation
      times tend to be longer. In this setting, as much as 140 minutes has been shaved
      off the symptom-to-needle time with a 50% reduction in 3-month mortality
      sustained as a 30% reduction in 5-year mortality. Most hospitals can improve
      their treatment (door-to-needle) time by focusing on chronic sources of delay. An
      emergency room culture of quick, coordinated response to chest pain must involve
      registration clerks, triage nurses, ECG technicians and emergency physicians. The
      authority to decide thrombolytic therapy must reside with the primary care
      physicians in any emergency room that encounters an acute infarction. The
      profound, life-saving benefits of thrombolytic therapy when used in a timely way
      should evoke a new sense of urgency in medical personnel when encountering the
      individual with a potential myocardial infarction.

PMID- 9585863
TI  - A review of the drug treatment of cachexia associated with cancer.
AB  - In the past 20 years, cachexia in cancer patients has attracted increasing
      interest from both clinicians and basic researchers. It is now clear that the
      cachexia is secondary to major metabolic abnormalities due to tumour by-products
      and cytokine release. These metabolic abnormalities produce numerous symptoms
      such as cachexia, anorexia and asthenia. There are now effective drugs such as
      corticosteroids and progestational drugs that have been shown to improve
      appetite, food intake and sensation of well-being, and which elicit bodyweight
      gain. While hydrazine (hydrazine sulfate) has received much attention,
      unfortunately it has been shown to be ineffective in improving the symptoms of
      the patient with cancer cachexia. A new group of drugs, such as thalidomide and
      melatonin because of their effects on tumour necrosis factor-alpha, and beta 2
      adrenoceptor agonists because of their effects on muscle metabolism, and other
      agents, is presently reaching the clinical trial stage. There is now the
      possibility of addressing this fascinating syndrome at a different level and an
      opportunity for combined therapy to try to improve the quality of life of these
      patients.

PMID- 9585866
TI  - Tazarotene.
AB  - Tazarotene is a topical retinoid that appears to exert its effects via retinoic
      acid receptors. It normalises differentiation and proliferation of keratinocytes
      and has an anti-inflammatory effect. Topical tazarotene 0.05% or 0.1% gel was
      effective in the treatment of plaque psoriasis in clinical trials and its
      therapeutic effect was maintained for at least 12 weeks after treatment
      discontinuation in some patients. In one study in patients with psoriasis,
      tazarotene had similar efficacy to fluocinonide in reducing plaque elevation, but
      not erythema. In another study, tazarotene was reported to be less effective than
      fluocinonide. Combination treatment with tazarotene plus a mid- or high-potency
      corticosteroid was more effective in the treatment of psoriasis than tazarotene
      alone. Topical tazarotene 0.1% gel significantly reduced lesion counts in
      patients with mild to moderate facial acne vulgaris. Skin irritation is a common
      adverse event with topical tazarotene, but it is mainly of mild to moderate
      severity. Tazarotene is not recommended for use in women who are, or may become,
      pregnant.

PMID- 9585865
TI  - Diagnosis and treatment of Whipple's disease.
AB  - Whipple's disease is a rare systemic infectious disease. To date, it has neither
      been possible to culture the bacillus Tropheryma whippelii, nor to infect other
      individuals with the pathogen. Today the diagnosis is confirmed by means of
      polymerase chain reaction (PCR) technology. Typically, the material for the PCR
      analysis comes from the duodenum. The diagnosis can also be established in this
      way on the basis of other tissue, or the cerebrospinal fluid. Treatment should
      only be carried out with antibiotics which cross into the cerebrospinal fluid,
      since there can also be an unrecognised involvement of the CNS. At present, the
      favoured method of treatment is the daily parenteral administration of 1.2
      million units of benzylpenicillin (penicillin G) and streptomycin 1 g for a
      period of 2 weeks. This is followed by treatment with cotrimoxazole (trimethoprim
      160 mg and sulfamethoxazole 800 mg) twice daily for 1 to 2 years. The treatment
      should begin and end with a PCR analysis of cerebrospinal fluid, in order to
      definitively diagnose infection of the CNS with Whipple's disease and to document
      the disappearance of the bacillus from the CNS.

PMID- 9585867
TI  - Eprosartan.
AB  - Eprosartan is a nonpeptide angiotensin II receptor antagonist which has a high
      affinity for the AT1 receptor subtype. When administered at dosages of 400 to 800
      mg/day (once or twice daily) for 13 weeks to patients with mild to moderate
      essential hypertension, eprosartan significantly reduced blood pressure compared
      with placebo. Eprosartan was at least as effective as enalapril 10 to 40 mg/day
      in a dose-titration study in patients with severe hypertension. Eprosartan is
      generally well tolerated; clinical trials have shown the drug to have a
      tolerability profile similar to that of placebo. As with other angiotensin II
      receptor antagonists, it does not cause cough. Eprosartan is not metabolised by
      the cytochrome P450 system and therefore has a low potential for drug
      interactions.

PMID- 9585868
TI  - Zanamivir.
AB  - Zanamivir is the first of a new class of selective influenza virus neuraminidase
      inhibitors. It inhibits both influenza A and influenza B virus replication in
      vitro. In the ferret model of influenza, zanamivir reduced viral replication and
      diminished pyrexia associated with the infection. Repeated passage of influenza
      virus in the presence of zanamivir could produce resistance in vitro. However,
      there have been no changes in sensitivity to zanamivir in any influenza virus
      isolates from patients receiving zanamivir in clinical trials. In experimental
      infection in humans, in which the virus replicates only in the nasal passages,
      intranasal zanamivir (3.6 to 16 mg) prevented infection with influenza virus. A
      combination of inhaled (10 mg) and intranasal (6.4 mg) zanamivir for 14 days was
      effective in preventing influenza in a nursing home setting during an influenza A
      virus outbreak. Inhaled zanamivir (10 mg) with or without intranasal zanamivir
      (6.4 mg) reduced the time to alleviation of influenza symptoms compared with
      placebo in patients with confirmed infection.

PMID- 9585869
TI  - Abacavir.
AB  - Abacavir is a nucleoside analogue reverse transcriptase inhibitor that inhibits
      clinical isolates of HIV in vitro with a potency similar to that of zidovudine.
      Resistance to abacavir develops relatively slowly. Cross-resistance between
      abacavir and didanosine, zalcitabine or lamivudine, but not zidovudine or
      stavudine, has been reported in vitro. Abacavir has good oral bioavailability, as
      demonstrated in animals, and penetrates the CNS. Treatment with abacavir, alone
      or in combination with other anti-HIV agents (zidovudine, lamivudine, nevirapine,
      amprenavir and/or other protease inhibitors), decreased viral load and increased
      CD4+ cell count in patients with HIV infection. Effectiveness was maintained for
      at least 48 weeks. In early phase I/II trials, headache, gastrointestinal
      disturbances, rash, malaise, fatigue and/or asthenia were the most common adverse
      events reported with abacavir alone or in combination with other anti-HIV agents.
      Hypersensitivity reactions lead to discontinuation of therapy in 2 to 3% of
      patients.

PMID- 9585870
TI  - Clinical assessment of patients.

PMID- 9585862
TI  - An overview of topical antifungal therapy in dermatomycoses. A North American
      perspective.
AB  - Dermatophytes cause fungal infections of keratinised tissues, e.g. skin, hair and
      nails. The organisms belong to 3 genera, Trichophyton, Epidermophyton and
      Microsporum. Dermatophytes may be grouped into 3 categories based on host
      preference and natural habitat. Anthropophilic species predominantly infect
      humans, geophilic species are soil based and may infect both humans and animals,
      zoophilic species generally infect non-human mammals. It is important to confirm
      mycologically the clinical diagnosis of onychomycosis and other tinea infections
      prior to commencing therapy. The identity of the fungal organism may provide
      guidance about the appropriateness of a given topical antifungal agent. Special
      techniques may be required to obtain the best yield of fungal organisms from a
      given site, especially the scalp and nails. It is also important to realise the
      limitations of certain diagnostic aids e.g., Wood's light examination is positive
      in tinea capitis due to M. canis and M. audouinii (ectothrix organisms); however,
      Wood's light examination is negative in T. tonsurans (endothrix organism).
      Similarly, it is important to be aware that cicloheximide in culture medium will
      inhibit growth of non-dermatophytes. Appropriate media are therefore required to
      evaluate the growth of some significant non-dermatophyte moulds. For tinea
      infections other than tinea capitis and tinea unguium, topical antifungals may be
      considered. For effective therapy of tinea capitis an oral antifungal is
      generally necessary. Similarly, oral antifungals are the therapy of choice,
      especially if onychomycosis is moderate to severe. Furthermore, where the tinea
      infection involves a large area, in an immunocompromised host or if infection is
      recurrent with poor response to topical agents, then oral antifungal therapy may
      be necessary. Topical antifungal agents may be broadly divided into specific and
      nonspecific agents. The former group includes the polyenes, azoles, allylamines,
      amorolfine, ciclopirox and butenafine. Generally the topical agent is available
      as a cream, sometimes for use intravaginally. Less commonly, the formulation may
      be in the form of a powder, lacquer, spray, gel or solution. Many of these agents
      have a broad spectrum of activity, being effective against dermatophytes, yeasts
      and Malassezia furfur. For the treatment of tinea corporis, tinea cruris tinea
      versicolor and cutaneous candidosis, once or twice daily application may be
      required, the most common duration of therapy being 2 to 4 weeks. For tinea pedis
      the most common treatment duration is 4 to 6 weeks.

PMID- 9585871
TI  - Assessment of airway inflammation: an overview.

PMID- 9585872
TI  - Methods for sputum induction and analysis of induced sputum: a method for
      assessing airway inflammation in asthma.

PMID- 9585873
TI  - Bronchoalveolar lavage: performance, sampling procedure, processing and
      assessment.

PMID- 9585874
TI  - Biopsies: bronchoscopic technique and sampling.

PMID- 9585875
TI  - Biopsies: processing and assessment.

PMID- 9585876
TI  - Bronchial brushing.

PMID- 9585877
TI  - In situ hybridization and the polymerase chain reaction.

PMID- 9585878
TI  - Endobronchial allergen challenge.
AB  - LEAC offers a very practical means of studying the pathophysiology of asthma.
      Despite the local nature of the challenge, LEAC often has a significant effect on
      FEV1 and may cause short-term destabilization of asthma. In common with other
      bronchoscopic methods used to study human asthma, samples obtained by LEAC show a
      considerable degree of variability and it is therefore necessary to use groups of
      12-15 subjects to minimize the risk of Type II statistical errors. Comparisons
      between different studies of allergen exposure are made difficult by a variety of
      technical considerations. Chief among these are subject selection, the technique
      used for allergen exposure, the timing of sampling, and the analysis techniques.
      Dose-response studies in nonasthmatic allergic subjects indicate that the degree
      of BAL eosinophilia is related to the dose of antigen [17] but there is as yet no
      agreement on how LEAC might be standardized. Notwithstanding these reservations,
      local endobronchial allergen challenge has already yielded valuable information
      on the pathophysiology of asthma and will remain a useful complement to other
      investigational techniques in the future exploration of this disease.

PMID- 9585879
TI  - Drug trials.

PMID- 9585880
TI  - Safety of biopsies and bronchoalveolar lavage.

PMID- 9585881
TI  - Peripheral blood markers: evaluation of inflammation in asthma.

PMID- 9585882
TI  - Exhaled nitric oxide as a marker in asthma.

PMID- 9585883
TI  - Methods for assessment of airways inflammation: paediatrics.

PMID- 9585884
TI  - Cork suberin as a new source of chemicals. 1. Isolation and chemical
      characterization of its composition.
AB  - Extractive-free cork from Quercus suber L. was submitted to a solvolysis
      treatment with methanolic NaOH which yielded 37% (o.d. cork) of suberin. This
      mixture of compounds was thoroughly characterized by FTIR, 1H- and 13C-NMR, gas
      chromatography coupled with mass spectrometric (GC-MS) analysis, vapour pressure
      osmometry (VPO), mass spectrography (MS) and gel permeation chromatography (GPC).
      After derivatization, the main components of the volatile fraction, representing
      less than half of the total, were found to be omega-hydroxymonocarboxylates,
      alpha, omega-dicarboxylates, simple alkanoates and 1-alkanols, all with chain
      lengths ranging from C16 to C24. A second fraction, with an average molecular
      weight about three times higher, was detected by VPO, MS and GPC. The presence of
      this important fraction in cork suberin had not been recognized in earlier
      studies. Both fractions constitute interesting precursors for the elaboration of
      new materials.

PMID- 9585885
TI  - Stability of polyomavirus major capsid protein VP1 under denaturants guanidine
      hydrochloride and urea.
AB  - The guanidine hydrochloride (GdnHCl)- and urea-induced equilibrium denaturation
      of recombinant polyomavirus (Py) major capsid protein VP1 was studied by circular
      dichroism and fluorescence spectroscopy. Both secondary and tertiary structures
      of PyVP1 were shown to be disrupted in the presence of denaturants. Although the
      far-UV circular dichroism (CD) spectra of PyVP1 in the denaturants exhibit
      similar two-phase transition as those obtained from the fluorescence
      measurements, the unfolding of PyVP1 in GdnHCl was shown to be more complex than
      a similar two-state mechanism. The presence of unfolding intermediates is
      manifested by the noncoincidence of transitions when detected by different
      probes. The unfolding intermediate appeared to be stabilized by 1 M NaCl.
      Addition of Ca2+ and 2-mercaptoethanol does not show significant effect on the
      conformational stability of PyVP1. Unfolding of PyVP1 in GdnHCl was shown to be
      an irreversible process.

PMID- 9585886
TI  - Development of the selective adsorbent for EDA containing fibronectin using
      heparin immobilized cellulose.
AB  - We have noticed that extra domain A containing fibronectin (EDA(+)FN) is closely
      related to inflammatory diseases and accordingly investigated a selective
      adsorbent to remove EDA(+)FN, which may increase the severity of the symptoms,
      from the plasma of rheumatoid arthritis (RA) patients. Three types of heparin
      immobilized cellulose (HC) were prepared and their adsorptive properties were
      evaluated by batchwise adsorption tests. The results showed that EDA(+)FN was
      adsorbed more efficiently than total FN on HC. In particular HC in which heparin
      was immobilized to amino residue had an excellent capacity. The adsorption rates
      of EDA(+)FN, total FN and antithrombin-III were 89, 15 and 17% respectively. This
      adsorbent is extremely useful in selectively removing EDA(+)FN from plasma.

PMID- 9585887
TI  - Factors affecting the specificity of beta-glucosidase from Fusarium oxysporum in
      enzymatic synthesis of alkyl-beta-D-glucosides.
AB  - Fusarium oxysporum beta-glucosidase has been used to catalyze the production of
      alkyl-beta-D-glucosides from various disaccharides, based on the
      transglucosylation reaction, in the presence of primary, secondary and tertiary
      alcohols as glucosyl acceptors. Primary alcohols were found to be the best
      acceptors. The influence of the glucosyl donor concentration, as well as the
      enzyme specificity towards the cleaved glucosidic bond and the aglucone part of
      the donor, have also been investigated. The enzyme does not exhibit
      regiospecificity and seems to be unspecific towards the aglucone part. The
      specificity of the beta linkage has been confirmed by proton nuclear magnetic
      resonance (1H NMR) analysis.

PMID- 9585888
TI  - Solution conformation of methylated macrolide antibiotics roxithromycin and
      erythromycin using NMR and molecular modelling. Ribosome-bound conformation
      determined by TRNOE and formation of cytochrome P450-metabolite complex.
AB  - Conformational study of methylated derivatives of macrolide antibiotics
      roxithromycin (6-OMe-roxithromycin and 6,11-OMe-roxithromycin) has been achieved
      by NMR in solution and molecular dynamics (MD) simulations and compared to 6-OMe
      erythromycin (clarithromycin). A complete conformational study by NMR has been
      led by determination of homonuclear coupling constants and NOEs. Heteronuclear 1H
      13C coupling constants were also measured to investigate the orientation of the
      sugar moieties with respect to the erythronolide. MD simulations were performed
      using the crystallographic coordinates as the starting conformation. For each
      compound, experimental results were compared to calculated conformations in order
      to identify eventual conformational equilibrium in solution. It is shown that the
      effect of the methylation is opposite for roxithromycin compared to erythromycin
      especially on motional properties as the roxithromycin derivatives gain in
      mobility while the erythromycin derivatives behaves as a more restrained
      molecule. The study of macrolide-ribosome interactions has been investigated
      using transferred NOESY 1H NMR experiments and the conformations weakly bound to
      bacterial ribosomes were determined. Biological interactions of these compounds
      with membranar liver protein cytochrome P450 was also discussed with regard to
      their structural properties.

PMID- 9585889
TI  - The adsorption of substrate-binding domain of PHB depolymerases to the surface of
      poly(3-hydroxybutyric acid).
AB  - The binding characteristic of PHB depolymerase has been studied by using
      glutathione S-transferase (GST) fusion proteins with substrate-binding domain of
      three bacterial PHB depolymerases, Alcaligenes faecalis, Comamonas acidovorans
      and Comamonas testosteroni. Analysis using immuno-gold labeling technique and
      transmission electron microscopy indicated that a novel GST fusion protein
      derived from A. Faecalis enzyme adsorbed to the surface of poly(3-hydroxybutyric
      acid) (P(3HB)) single crystals like other fusion proteins. Comparison of
      inhibiting degree of P(3HB) powder hydrolysis activity of PHB depolymerase by
      fusion proteins indicated that three fusion proteins bind to P(3HB) powder in the
      same degree. The measurement of the surface hydrophobicity of proteins suggests
      that the interaction of the substrate-binding domain with insoluble P(3HB) may
      include not only a hydrophobic effect but also molecule-specific contacts.

PMID- 9585890
TI  - The role of pH, temperature and nucleation in the formation of cholesteric liquid
      crystal spherulites from chitin and chitosan.
AB  - The alpha chitin and chitosan used in the experiments came from crab shell waste
      (Sigma). This was treated to form a colloidal suspension of chitin or chitosan
      crystallites. The electrostatic 'charge coat' surrounding the chitin was then
      manipulated. This was achieved by alteration of the pH of the chitin or chitosan
      colloid (Chitin pKa = 6.1). This allowed the charge density on the crystalline
      rod of chitin or chitosan to be altered. The effect of this treatment was
      ascertained by measuring the diameter of spherulites formed in vitro. The results
      were analysed to see if the experimental optimal pH agreed with theoretical
      approximations. Further investigations were carried out on the initiation of the
      spherulites and the effect of temperature on spherulite formation. The
      spherulites form via self assembly through a liquid crystalline cholesteric
      phase. Manipulation of the electrostatic coat of the chitin could be a method of
      cellular remote control for formation of the helicoid in arthropod cuticle. This
      would allow the arthropods to set up conditions that aid the self assembly
      process.

PMID- 9585891
TI  - Cyclodextrins: new drug delivery systems in dermatology.

PMID- 9585892
TI  - Uremic pruritus.

PMID- 9585893
TI  - Acne fulminans.

PMID- 9585894
TI  - Nehushtan: Joshua, meaningful survival, and dermatology.

PMID- 9585895
TI  - Immunoperoxidase evaluation of lichen planus biopsies for hepatitis C virus.
AB  - BACKGROUND: Lichen planus is a papulosquamous dermatosis which has recently been
      linked to infection with hepatitis C virus. It is unclear whether or not viral
      antigens may be present in the cutaneous lesions of lichen planus. MATERIALS AND
      METHODS: Twenty-five paraffin-embedded samples of glabrous lichen planus were
      evaluated using immunoperoxidase staining for the presence of hepatitis C
      virions. Control tissues consisted of hepatitis C-infected hepatic tissue (n =
      2), normal hepatic tissue (n = 2), normal human skin (n = 1), and two cutaneous
      biopsies of lichen planus from persons known to be infected with hepatitis C.
      RESULTS: The sections of hepatitis C-infected liver tissue stained positive for
      hepatitis C virions. The 25 biopsies of glabrous lichen planus, the two biopsies
      of lichen planus from hepatitis C patients, the two sections of normal liver, and
      the one normal skin sample all failed to take up the stain. CONCLUSIONS:
      Cutaneous lesions of lichen planus are more probably reactive to the underlying
      infection than a manifestation of skin involvement by this disease. This theory
      is supported by the histologic findings in a lichenoid drug eruption, which are
      virtually identical to those of idiopathic lichen planus. Insufficient
      sensitivity by the immunoperoxidase procedure used is a possible explanation for
      our results; however, it appears more probable that no virus exists at the sites
      of cutaneous involvement.

PMID- 9585897
TI  - A polypous carbuncle.
AB  - A carbuncle usually presents as a deep-seated mass of fistulous tracts between
      infected hair follicles. We present a case in which what appeared to be an
      inflamed, benign neoplasm turned out to be a very unusual presentation for this
      condition, the first we could find in the literature. A 62-year-old woman
      presented with a bothersome 'mole' on her flank of uncertain duration but it was
      initially pruritic and irritated by her clothing. Owing to the pain, she wanted
      its removal. A 1 cm soft, pink, stalked papule revealed multiple, closed,, comedo
      like spots on its surface (Fig. 1). The lesion was mildly tender and freely
      mobile on a broad-based stalk. A pre-biopsy diagnosis of irritated intradermal
      nevus or neurofibroma was made, and the lesion was blade-shaved flush with the
      skin surface. Histologically, the papule demonstrated small abscesses which
      seemed to connect, as well as foci of granulation tissue and marked dermal edema
      (Fig. 2). Fragments of infundibular epidermis were found throughout the lesion.
      No residual melanocytic or neural neoplasms were identified.

PMID- 9585896
TI  - Capillaropathy and capillaroneogenesis in the pathogenesis of rosacea.
AB  - BACKGROUND: Dilatation of vascular vessels in rosacea has generally been
      attributed to yielding to deranged connective tissue. In contrast, in a previous
      study a degrading effect of insufficient vascular vessels in connective tissue
      has been demonstrated in connection with diabetic microangiopathy. In yet another
      paper, it was demonstrated that the fusing of damaged capillaries, which had lost
      part of their adjacent walls due to functional inadequacy, led to the formation
      of dilated vessels. These pathogenetic patterns are the main subjects of this
      study of rosacea. METHODS: Punch biopsies from rosacea lesions were examined by
      light microscopy and immunochemistry in order to identify structural changes
      leading to the formation of telangiectasias. RESULTS: Deranged connective tissue
      is secondary to damaged capillaries. The primary damage may be evoked mostly by
      environmental influences, mainly the sun. CONCLUSIONS: Infections, infestations,
      and granulomatous formations are not primary in the development of rosacea.

PMID- 9585898
TI  - Papillon-Lefevre syndrome.

PMID- 9585899
TI  - Extranodal Rosai-Dorfman disease (RDD) of the skin.

PMID- 9585900
TI  - Adult T-cell leukemia with predominant skin involvement.

PMID- 9585901
TI  - Primary therapy of malignant melanomas: sentinel lymphadenectomy.
AB  - BACKGROUND: Each melanoma is drained by one or, occasionally, several individual
      lymph nodes within the nearest lymph node region (sentinel lymph node).
      OBJECTIVE: By histopathologic examination of the removed sentinel lymph node
      (SLN), it is possible to select patients clinically according to stage I or II
      (UICC classification), but who, microscopically, represent stage III. METHODS:
      Sentinel lymphadenectomies (SLNEs) were performed initially by the vital blue dye
      technique, and later by gamma-probe guidance only. The removed SLNs were examined
      by hematoxylin and eosin as well as immunohistochemical stains (S100, and HMB
      45). RESULTS: We have performed 115 gamma-probe-guided SLNEs in 100 patients. The
      SLN could be found in all cases. In pT3 + 4 melanomas, 27.5% of the SLNs were
      positive; in only one patient with a pT2 tumor were micrometastases found.
      CONCLUSIONS: gamma-Probe-guided SLNE is a reliable procedure with minimal
      complications that should be performed in all pT3 + 4 (intraoperative frozen
      section histology) melanomas without clinically evident metastases.

PMID- 9585902
TI  - Cryosurgery in oral lesions.
AB  - BACKGROUND: Cryosurgery is a therapeutical method successfully used for many
      cutaneous conditions. Its use is increasing for several conditions in the oral
      cavity. METHODS: Liquid nitrogen spray or cryoprobe have been used alone or
      associated with other surgical methods in various types of oral lesions, such as
      pyogenic granuloma, angioma, actinic cheilitis, keratoacantoma, fibroma, HPV
      lesions in HIV and non-HIV patients, hypertrophic lichen planus, leukoplakia and
      erythroplakia, verrucous carcinoma, mucous cysts, and papillary hyperplasia of
      the palate, among others. RESULTS: Our experience and the literature have shown
      that cryosurgery is a very useful technique for treatment of oral lesions. The
      oral mucosa, because of its characteristics of humidity and smoothness, is an
      ideal site for this technique. It shows a very good esthetic result and it may be
      either the first choice or an alternative option to conventional surgery.
      CONCLUSIONS: Cryosurgery is a very safe, easy to perform, and relatively
      inexpensive technique for treating various oral lesions in an out-patient clinic.

PMID- 9585903
TI  - Short- and long-term histologic effects of topical tretinoin on photodamaged
      skin.
AB  - BACKGROUND: A series of clinical trials lasting up to 4 years had demonstrated
      that topical tretinoin improves facial appearance by reducing the visible signs
      of photodamage. OBJECTIVE: This paper reviews the studies designed to explore the
      relationship between clinical improvement and histologic changes. METHODS:
      Histologic changes in biopsies taken at various time points from clinical trial
      participants were examined by pathologists blinded to treatment regimens.
      RESULTS: Histologic evaluations of photodamaged skin during the course of
      treatment with tretinoin have revealed an array of time-dependent morphologic
      changes which can be classified as early, intermediate, and late. Initial changes
      in fine wrinkling and texture appear to correlate with epidermal mucin and
      compaction of the stratum corneum, but the latter is transient and ultimately
      returns to pre-treatment levels. Alterations in dermal matrix components have
      been noted with prolonged treatment. Partial restoration of the dermal collagen
      by new synthesis may contribute to the sustained improvement in fine wrinkling
      noted even when the treatment frequency is reduced from daily to three times
      weekly. As treatment is continued beyond 24 months, the collagen organization
      continues to improve and elastosis continues to decrease. Increases in epidermal
      and dermal mucin and decreases in epidermal melanin are consistent throughout the
      treatment period. The reduction in the hyperpigmentation of photodamage is
      comparable with the histologic and clinical improvements seen when tretinoin is
      used to treat conditions such as melasma. No adverse effects on the
      histopathology of the skin are noted with long-term exposure to tretinoin.
      Neither keratinocyte nor melanocyte atypia is detected. CONCLUSIONS: Although
      there does not seem to be a direct correlation between histologic changes and
      clinical improvement, the major structural changes appear to be directed at
      restoring the skin to the pre-sun-damaged state.

PMID- 9585904
TI  - Cutaneous reactions at the site of post-infection gp160 vaccination therapy in
      HIV-1+ patients. Military Medical Consortium for the Advancement of Military
      Medicine.
AB  - BACKGROUND: Post-infection vaccination with human immunodeficiency virus type 1
      (HIV-1) specific antigens has been hypothesized as a mechanism for generating a
      more effective immune response to the HIV-1 virus. Cutaneous reactions at the
      site of immunization may provide information on the pattern of immune activation
      induced by the vaccine. OBJECTIVE: To evaluate exaggerated local cutaneous
      reactions in eight HIV-1+ patients enrolled in a phase I and II gp160 vaccine
      study. METHODS: Cutaneous biopsy specimens were obtained and evaluated using
      routine histologic, immunofluorescence, and immunohistochemical techniques.
      RESULTS: A mononuclear cell infiltrate with tissue eosinophilia, in some cases
      forming flame figures, was present on histologic sections. There was no evidence
      of immune complex deposition. Activated T-helper cells formed a major portion of
      the mononuclear cell infiltrate. CONCLUSIONS: A delayed-type hypersensitivity
      reaction, mediated by T cells with a T-helper 2 cytokine pattern, was favored by
      clinical and histologic features. The most likely antigen stimulating this
      reaction is residual lepidopteran used in the preparation of the vaccine;
      however, baculovirus antigens may also play a role. In addition, the adjuvant,
      aluminum phosphate, as well as the underlying patterns of immune dysregulation
      present in HIV-1+ patients, may potentiate these reactions.

PMID- 9585905
TI  - Azathioprine in the treatment of Parthenium dermatitis.
AB  - BACKGROUND: Parthenium dermatitis is a chronic disorder whose management is
      extremely difficult. Allergen avoidance is almost impossible, topical
      corticosteroid therapy provides only partial relief, and prolonged systemic
      corticosteroid therapy has unacceptable side-effects. METHODS: Twenty patients
      with chronic Parthenium dermatitis, with relative contraindications to systemic
      corticosteroids or their side-effects, were treated with oral azathioprine (100
      150 mg daily). The severity of dermatitis was assessed at 0, 1, 3, 6, and 12
      months using a modified PASI scoring system. RESULTS: The mean age of the
      patients was 54 years (range, 40-72 years) and the mean duration of dermatitis
      was 7.6 years (range, 3 months to 36 years). The mean initial score was 18.9
      (range, 3.3-42), which decreased to 8.8 (range, 1.6-18.2) at 3 months, 4.8
      (range, 0.6-14.6) at 6 months, and 0.7 (range, 0.2-1.4) at 12 months. Of the 15
      patients evaluated at 6 months, all but one showed a response. Ten (66.6%)
      patients showed near-total clearance, i.e. reduction in score by more than 90%,
      and three patients (20%) showed more than 50% reduction in score. No significant
      side-effects were noted. CONCLUSIONS: Azathioprine is an effective and safe
      alternative to corticosteroid therapy in the treatment of chronic Parthenium
      dermatitis. It is especially useful in patients with side-effects or
      contraindications to corticosteroid therapy.

PMID- 9585906
TI  - Itraconazole for the treatment of onychomycosis.
AB  - BACKGROUND: The broad spectrum of activity of itraconazole in vitro manifests
      itself clinically with the drug being effective for the treatment of
      onychomycosis caused by dermatophytes, Candida and some non-dermatophyte molds.
      The pharmacokinetics of itraconazole in the nail results in drug remaining at
      therapeutic levels for 6-9 months after completion of therapy. METHODS: An
      overview of studies where continuous or pulse itraconazole therapy has been used
      in the treatment of fingernail and toenail onychomycosis. RESULTS: Following
      continuous therapy at 200 mg/day for 3 months for toenail onychomycosis (n =
      1741), the rates of clinical cure, clinical response and mycologic cure were:
      (meta-average +/- 95% standard error (SE)), 52 +/- 9%, 86 +/- 2%, and 74 +/- 3%,
      respectively, at follow-up 12 months following start of therapy. In fingernail
      onychomycosis (n = 211), the duration of therapy was 6 weeks and the
      corresponding efficacy rates at follow-up, 9 months after start of therapy, were
      meta-average (+/- S.E.) 82 +/- 5%, 90 +/- 2%, and 86 +/- 3%, respectively. In
      toenail onychomycosis treated with 3 pulses of therapy (n = 1389), the clinical
      response, clinical cure and mycologic cure were observed in meta-average (+/-
      S.E.) 58 +/- 10%, 82 +/- 3%, and 77 +/- 5% patients, respectively, at follow-up
      12 months after the start of therapy. In fingernail onychomycosis treated with 2
      pulses of therapy (n = 210), at follow-up 9 months after the start of therapy,
      the corresponding efficacy rates were meta-average (+/- S.E.) 78 +/- 10%, 89 +/-
      6%, and 87 +/- 8%, respectively. CONCLUSIONS: Both the continuous and pulse
      therapy regimens are safe with few adverse effects. Compared to continuous
      therapy, the pulse regimen has an improved adverse-effects profile, is more cost
      effective, and is preferred by many patients.

PMID- 9585907
TI  - Textiles and apparel in the etiology of skin diseases 1870-1914.

PMID- 9585908
TI  - Knuckle pad-like keratoderma: a new cutaneous side reaction induced by tegafur.

PMID- 9585909
TI  - Hairy elbows.

PMID- 9585910
TI  - Urban bus driving: an international arena for the study of occupational health
      psychology.
AB  - This article offers a brief summary of the articles in this special issue, plus
      it provides a rationale for the scientific study of urban bus operation. Among
      the reasons to study urban transit operators are the following:
      Multimethodological, international data show that urban bus driving is an
      unhealthy occupation; psychosocial and environmental characteristics of the
      transit work setting portend ill health, plus these characteristics are readily
      discernible to the public; urban transit workforces well represent blue-collar
      populations; despite widespread changes in the nature of work related to
      technological innovations, mass-transit operation is likely to remain stable, and
      the "health" of the mass-transit industry has important implications for societal
      well-being; and finally, bus driving illustrates several important methodological
      challenges. The article concludes with an overview of future research.

PMID- 9585911
TI  - Bussy business: how urban bus drivers cope with time pressure, passengers, and
      traffic safety.
AB  - Adhering to the schedule, providing service to passengers, and driving safely are
      among the most important psychosocial demands of the bus driver's job. The ways
      bus drivers cope with these varying and conflicting demands are addressed in this
      article, which uses data from 4 interrelated studies. In a large-scale
      questionnaire study (Study 1), behavioral styles in coping with these
      psychosocial demands were identified. Next, in Studies 2 and 3, the relations of
      these styles with well-being and health status were examined. Study 4 addressed
      the coping process during work itself by examining the relations among objective
      workload indicators, perceived effort, and psychophysiological stress reactions
      during work.

PMID- 9585912
TI  - Psychophysiological stress reactions in female and male urban bus drivers.
AB  - Male and female urban bus drivers were studied at work during everyday bus
      driving in urban traffic (work condition) and watching educational programs
      (comparison condition). The results showed that (a) both sexes had significantly
      higher adrenaline, noradrenaline, and cortisol excretion levels during work than
      during the comparison session; (b) during work and inactivity, there were no
      significant sex differences in hormone excretion for either hormone; (c) the
      percentage increase during work compared with control levels for all hormones was
      equally high in the female group as in the male group; and (d) there were no
      significant sex differences in self-reported mood (distress, well-being, control)
      during bus driving. The results are discussed in terms of type and intensity of
      stressors, gender differences in costs of adaptation, preventive measures, and
      the role of social influences in psychoneuroendocrine regulation.

PMID- 9585913
TI  - Objective stress factors, accidents, and absenteeism in transit operators: a
      theoretical framework and empirical evidence.
AB  - The authors used observational job analysis as a conceptually based technique to
      measure stress factors unbiased by worker appraisal with 81 transit driving tasks
      on 27 transit lines. Stressor dimensions included work barriers that interfere
      with task performance due to poor technical-organizational design, time pressure,
      time binding (autonomy over time management), and monotonous conditions. Line
      specific average stressor values were assigned to 308 transit operators who
      mainly worked the particular line. Logistic regression analyses showed
      associations for high work barriers and sickness absences (odds ratio [OR] = 3.8,
      p = .05). There were elevated risks for work accidents for high time pressure
      operators (OR = 4.0, p = .04) and for the medium time-binding group (OR = 3.3, p
      = .04) and significant (alpha = .20) unadjusted interaction terms for barriers
      and time pressure in predicting accidents and absences, and barriers and time
      binding in predicting absences. Findings suggest guaranteed rest breaks and
      flexible timing for accident prevention and removal of work barriers for reducing
      absenteeism.

PMID- 9585914
TI  - Psychophysiologic sensitization to headlight glare among professional drivers
      with and without cardiovascular disease.
AB  - Previous studies have shown that young, healthy professional drivers show
      heightened central nervous system arousal and cardiovascular hyperreactivity to
      simulated headlight glare. Electroencephalographic and cardiovascular response
      and recovery to simulated headlight glare (the glare pressor test) were examined
      in 4 groups of male professional drivers (age 25-52 years)--12 with ischemic
      heart disease (IHD), 12 with hypertension (HTN), 10 with borderline hypertension
      (BHTN), and 34 who were healthy--and in 23 non-professional driver controls--with
      the aim of assessing sensitization to this night driving stressor in relation to
      degree of cardiovascular disease severity. After glare exposure the IHD drivers
      showed the most pronounced alpha blockade, a rise in diastolic blood pressure
      (DBP; p < .05), and, unlike the other groups, a persistent fall in finger pulse
      volume (p < .02). The BHTN group reacted initially with DBP rise and finger pulse
      drop (ps < .05 and .02, respectively), mainly without central nervous system
      arousal. The DBP remained constant in normotensive professional drivers older
      than 40. The drivers' cardiovascular responses to glare were inversely related to
      reported stressors and subjective experience. Anxiety trait and long work hours
      were associated with heightened central arousal to glare in professional drivers.
      The results suggest that there may be progressive degrees of sensitization to
      glare exposure in these samples, with the least among normotensive professional
      drivers older than 40, moderate levels in borderline hypertensives, and the most
      severe in drivers with IHD.

PMID- 9585915
TI  - The human side of the road: improving the working conditions of urban bus
      drivers.
AB  - This study evaluated how urban bus drivers' well-being was affected by technical
      interventions designed to improve the traffic environment of an urban bus route.
      Three questionnaires were distributed; 8 drivers at the intervention route (mean
      age 43 years) and 13 demographically matched comparison drivers (mean age 39
      years) participated at all occasions. Field studies at work were conducted twice,
      with 10 intervention route drivers (mean age 43 years) and 31 comparison drivers
      (mean age 42 years). The authors hypothesized that during the course of the
      intervention, the initially elevated indexes of occupational stress in the
      intervention group would be reduced to levels equivalent to those of the
      comparison group. The hypothesis was confirmed for perceived workload in the
      questionnaire, observer-rated job hassles, systolic blood pressure and heart rate
      at work, and perceived distress after work in the field study.

PMID- 9585917
TI  - [159th Reunion of the Association of the Rhein-Westfallen Ophthalmologists.
      Dusseldorf, 26/27 April 1997].

PMID- 9585916
TI  - Studies of health outcomes in transit operators: policy implications of the
      current scientific database.
AB  - Urban transit operators' medical symptoms and conditions exceed other
      occupational groups, resulting partly from working conditions. Medical outcomes
      among operators have an impact on the transit system, including on performance,
      work attendance, and medical costs. This is exacerbated by external economic and
      political pressures in which expected service often exceeds the system's capacity
      in a congested, chaotic urban environment. A vicious cycle of poor working
      environment, reduced health and well-being among operators, and lowered
      efficiency and increased costs often results. Operator-health policies focusing
      solely on individuals are not sufficient to address these problems. A broader
      approach is needed, acknowledging the relationship between health of the system
      and health of employees, including redesigning the interface between transit
      systems and the urban environment and organizational change within companies.
      This comprehensive approach recognizes the dynamic reciprocity among the transit
      operators, the transit system, and the larger community.

PMID- 9585918
TI  - [12th Congress of the German-language Society for Intraocular Lens-implantation
      and Refractive Surgery. Halle/Saale, 12-14 March 1998].

PMID- 9585919
TI  - Neurobiology of cocaine-induced organic brain impairment: contributions from
      functional neuroimaging.
AB  - The present review is directed at imparting the current knowledge regarding
      functional neuroimaging as a tool for enhancing the understanding of
      cerebrophysiologic and neurobehavioral consequences of stimulant abuse.
      Stimulants like cocaine are capable of inducing clinically significant
      neurocognitive impairment through direct action on the brain, and indirectly
      through other organs that influence cerebral physiology. Neurochemical
      dysregulation including profound effects on the serotonergic and dopaminergic
      systems have substantial physiological and neurobehavioral consequences. Brain
      hemorrhages, transient ischemic attacks, strokes,and seizures frequently follow
      cocaine use. The residual cerebropathologic consequences of cocaine are seen only
      in significant or pronounced brain events when structural neuroimaging techniques
      such as computed tomography (CT) and magnetic resonance imaging (MRI) are
      employed. However, recent research with newer functional neuroimaging techniques
      such as single photon emission, positron emission tomography, and quantitative
      electroencephalography have revealed high rates of significant alteration in
      brain function among cocaine users, with negative structural imaging studies.
      These findings are often associated with impairment on neuropsychological
      evaluation, also in the absence of positive findings on CT and MRI. Both cerebral
      metabolic and hypoperfusion anomalies are seen, especially in anterior and
      temporal brain regions. Observed changes can persist for months, and for some
      patients, may represent a permanent change in brain functioning.

PMID- 9585920
TI  - Olfaction in persons with Alzheimer's disease.
AB  - The need for low cost, noninvasive procedures for aiding in the diagnosis and
      understanding of Alzheimer's Disease (AD) has led to theories and procedures
      examining the role of olfactory disorders because of the finding that the brains
      of AD patients invariably exhibit neuropathology in the hippocampus and
      entorhinal cortex. This loss correlates with the increase in the number of
      plaques and tangles and with the severity of dementia. Considered together, these
      findings suggest that brain structures closely related to the olfactory system
      demonstrate significant histopathology in AD. A comprehensive review of the
      literature pertaining to olfaction in persons with AD revealed that the olfactory
      identification ability of patients with memory disorders is impaired relative to
      controls. Consistency is lacking, however, when olfactory detection thresholds
      are investigated. Also, there is inconsistency in regards to severity of illness
      and olfactory function. In addition to differentiating AD patients from normals,
      the olfactory paradigm has shown some limited usefulness in differentiating AD
      patients from some other demented patients.

PMID- 9585922
TI  - [Trends in orthopedics for rheumatoid diseases].

PMID- 9585923
TI  - [Rheumatoid arthritis. Conservative therapeutic possibilities today and in the
      future].
AB  - During the past few years the treatment of rheumatoid arthritis, the most
      frequent of the rheumatic inflammatory systemic diseases has improved a great
      deal. The treatment strategy is based on the one hand on the so-called prognostic
      factors and on the other hand on the extent of the inflammatory activities,
      especially during the first phase. Numerous controlled studies and meta-analyses
      have enabled optimal application of the basic disease-modifying drugs, with
      regard to efficacy and side effects. During the first stage of these disease, the
      immunobiological substances against pro-inflammatory cells are employed. Improved
      knowledge of physiotherapeutic treatment, correct diet and careful observation of
      the patient's progress with the aid of questionnaires enable optimal care with
      regard to life quality.

PMID- 9585924
TI  - [The rheumatic hand].
AB  - The hand (wrist and fingers) is one of the regions most frequently affected by
      rheumatic arthritis (RA). The nature of the alterations involved means it is
      possible to interpret the clinical picture as RA even from the external
      appearance. Obviously the functional handicap affects activities of daily living,
      and the insult to the patient's aesthetic sensibilities imposes an additional,
      psychological, burden. A generally satisfactory limitation of damage can only be
      expected from professionals who work well together as a team. The ability to
      devise a therapy plan with the right priorities is the mark of those who have
      mastered the art of surgery for rheumatic conditions. Operative treatment
      presupposes failure of a conservative therapy carried out according to modern
      views. In addition to operations on the affected joints, operations on the
      tendons of the hand are also highly significant in terms of function. The
      interventions that can be performed on the joints embrace synovectomies,
      arthroplasties and arthrodeses. In the last 20 years the absolute number of joint
      synovectomies has fallen, since at least in treatment of the early stages
      radiosynoviorthesis has become increasingly important, especially for the
      metacarpophalangeal (MP) and proximal interphalangeal (PIP) joints. Operative
      synovectomy is now considered when radiosynoviorthesis fails or in more advanced
      stages (Larsen 3) and when reconstruction procedures (especially on the tendons)
      are necessary. The chances are also better with open synovectomy (with or without
      resection of the head of the ulna) at the wrist. The results of synovectomy are
      not so impressive from the radiological aspect as from the clinical viewpoint,
      since as a result of the removal or attenuation of pain the function is often
      improved to the status of more than 10 years before and valuable time is thus
      gained. When the destruction is too far advanced arthroplasty is considered,
      especially for the MP joints but increasingly also for the PIP joints.
      Arthrodesis is a still highly valuable procedure for the wrist, since there is no
      really satisfactory artificial joint. An arthroplasty can only be successful if
      the tendons are intact. Tenosynovectomy and repair of ruptures have a good
      prognosis if appropriate techniques are used. The correction of such typical
      deformities of the fingers as buttonhole and swan neck deformity requires some of
      the technically more demanding operations.

PMID- 9585925
TI  - [The Schulthess classification of chronic polyarthritis of the wrist joint].

PMID- 9585921
TI  - Anterior temporal lobectomy, hippocampal sclerosis, and memory: recent
      neuropsychological findings.
AB  - Anterior temporal lobectomy (ATL) is an effective and increasingly utilized
      treatment for nonlesional, intractable mesial temporal lobe epilepsy. However,
      this surgery results in domain-specific neuropsychological morbidity for a subset
      of patients. Within the past decade, multidisciplinary studies have revealed that
      left ATL patients without significant sclerosis in the resected hippocampus are
      most at risk for a substantial postacute decline in the ability to encode new
      verbal information. These patients are also at risk for a significant decrement
      in confrontation naming and other retrieval-based language abilities. The memory
      deficit is not attributable to this disruption of language. A relationship
      between hippocampal sclerosis (HS) status and memory performance has not been
      identified consistently in right ATL patients, but investigation of new
      visuospatial measures continues. The influence of variables other than HS on
      neuropsychological outcome is also discussed.

PMID- 9585926
TI  - [Surgical procedures in the cervical spine in polyarthritis. Indications and
      surgical strategy].
AB  - Patients with rheumatoid arthritis suffer frequently from instabilities and
      deformities of the cervical spine which require surgical treatment. The most
      frequent indication for surgery represents the transverse atlantoaxial
      instability. As long the atlantoaxial instability remains reducible in extension
      a limited posterior exposure and screw fixation is adequate. Only situations with
      fixed dislocations and signs of myelopathy require anterior transoral
      decompression with simultaneous occipitocervical fusion. In the lower cervical
      spine, kyphotic deformities require anterior decompression and posterior
      stabilization in the case of electrophysiologically confirmed neurological
      deficits. A combined procedure with anterior vertebrectomy and decompression and
      posterior plate fixation is indicated since the poor bone quality rarely allows
      anterior stable fixation.

PMID- 9585927
TI  - [Ankle prostheses. Mid-term results after Thompson-Richards and STAR prostheses].
AB  - Thirty-seven patients with 20 cemented Thompson-Richards prostheses and 19
      cementless S.T.A.R. prostheses (2 bilateral cases) were followed up after 1-12
      years. Rheumatoid arthritis was the main diagnosis in both populations, with
      females dominating. The investigation was based on the Kofoed ankle score. At
      follow-up the total scoring improved to 86.9 pts. in S.T.A.R. and to 77.7 pts. in
      T.R.P. replacement. The radiological examination showed a high rate of
      radiolucency for the tibial component (53.3%) in cemented T.R.P.; subsidence of
      talar component was seen in 3 cases with T.R.P. In cementless S.T.A.R. prothesis
      only 3 cases showed small radiolucent lines of the flat tibial component. Talar
      subsidence was not seen at all. In T.R.P. we had two revisions due to prothesis
      loosening and one maleollar fracture, giving a cumulative estimated survival rate
      of 87% at 12 years. In the S.T.A.R. prosthesis group two revisions had to be
      performed because of one meniscal breakage and correction of meniscal height. The
      estimated survival rate at 6 years was 94.3%.

PMID- 9585928
TI  - [Combined arthroscopic and radiation synovectomy in rheumatoid arthritis].
AB  - In rheumatoid arthritis of the knee joint good results are obtained using
      arthroscopic synovectomy or radiation synovectomy. Aim of our study was to
      investigate, whether the combination of these two minimal invasive interventions
      achieves better results. First we performed arthroscopic synovectomy of the knee
      joint followed by radiation synovectomy with application of 111-222 MBq Yttrium
      90 6 weeks later. In a prospective randomised clinical trial between 1987 and
      1991 we performed radiation synovectomy on 22 knee joints and combined
      arthroscopic and radiation synovectomy on 26 knee joints. We explored the
      patients preoperatively, 6 weeks and 6 months postoperatively. In 1996 we
      evaluated 141 knee joints in a retrospective clinical trial. 90 Knee joints had
      been treated with the combined therapy, 39 only with radiation synovectomy and 12
      only with arthroscopic synovectomy. Depending on the three different therapeutic
      interventions, the patients were classified into midterm (3-5 years) and long
      term (6-8 years) observation groups. The trials are based on the standardized ARO
      Questionnaire of the knee joint, the modified ARO Knee-Score and the radiological
      grading according to Larsen, Dale and Eek. In the prospective clinical trial we
      found significant better results for patients treated with the combined therapy
      than for patients treated with radiation synovectomy only regarding the parameter
      swelling, effusion, range of motion, pain and Knee-Score. In the long-term
      results of the retrospective clinical trial the patients treated with the
      combined therapy showed a significant better outcome for the parameters pain,
      swelling and Knee-Score, than the patients treated with radiation synovectomy.
      Although no statistically significant difference was found comparing the results
      of the combined therapy with arthroscopic synovectomy, an improvement of the
      clinical outcome can be observed performing arthroscopic synovectomy followed by
      radiation synovectomy. In the treatment of rheumatoid arthritis of the knee joint
      a better outcome is achieved performing combined arthroscopic and radiation
      synovectomy than performing only one of the methods.

PMID- 9585929
TI  - [Patellar luxation].

PMID- 9585930
TI  - ["Guidelines, codes of practice, standards". Risk or chance for physician and
      patient?].
AB  - As far as the law concerning liability is concerned, guidelines, codes of
      practice, and medical standards are not contrasting concepts, nor do they
      indicate material differences; instead, those terms describe more or less
      precisely the care that a physician is required to exercise when treating
      patients and that a judge is required to assess in a trial. Guidelines, codes of
      practice, and standards thus take effect not directly, but indirectly, in that
      both physician and judge retain a certain discretion in making decisions in a
      particular case. The current obsession with guideline--primarily based on
      economic considerations and present in all specialist areas--together with the
      increasingly detailed rules that are being issued, carries the risk that to
      medical profession may of its own doing become too restricted, that physicians
      will become limited in their choice of treatment, and that the criteria by which
      liability is assessed will become stricter, thus increasing the physician's risk
      of being held liable under civil or criminal law. We need to prevent a
      development taking place in which "medical standards" become "standardized
      medicine", leading to a situation in which only what is stipulated in the form of
      a guideline or a code of practice will be paid for (and hence only that can be
      done).

PMID- 9585931
TI  - Vertical transmission of Toxoplasma gondii from chronically infected house (Mus
      musculus) and field (Apodemus sylvaticus) mice determined by polymerase chain
      reaction.
AB  - Captive-bred Mus musculus (house mice) and Apodemus sylvaticus (field mice) were
      each infected with 50 oocysts of Toxoplasma gondii M1 strain per os and infection
      in them and their offspring was assessed by polymerase chain reaction (PCR)
      amplification of the T. gondii B1 gene in brain tissue and by serology, using the
      modified agglutination test (MAT). The chronically infected female A. sylvaticus
      (n = 10) and M. musculus (n = 23) were mated at least 6 weeks after infection
      (and subsequently to produce up to 6 litters) and their pups examined 3 weeks
      after weaning at 6 weeks of age. By PCR, in offspring of A. sylvaticus and M.
      musculus respectively, vertical transmission was demonstrated in 82.7% (n = 83)
      and 85.0% (n = 207) of all pups (N.S., P > 0.05), 95% (n = 21) and 100% (n = 30)
      of all litters (N.S., P > 0.05), with a mean (+/- S.E.) proportion of each litter
      infected of 0.87 (0.06) and 0.86 (0.04) (N.S., P > 0.05). There was no change in
      any of these variables between first and subsequent litters. By serology, whilst
      MAT suggested 100% vertical transmission in A. sylvaticus, it under-estimated
      rates of infection in offspring of M. musculus. A limited series of bioassays
      from M. musculus tissues confirmed the good correlation of PCR and the poor
      correlation of MAT with mouse inoculation. These results indicate that vertical
      transmission in A. sylvaticus and M. musculus is extremely efficient and probably
      endures for the life of the breeding female. This mechanism favours parasite
      transmission and dispersion by providing a potential reservoir of infection in
      hosts predated by the cat.

PMID- 9585933
TI  - Intra- and inter-specific variation in nuclear ribosomal internal transcribed
      spacer 1 of the Schistosoma japonicum species complex.
AB  - The first internal transcribed spacer (ITS1) of the nuclear ribosomal DNA repeat
      was sequenced for members of the Schistosoma japonicum species complex (S.
      malayensis, S. mekongi and 2 geographical isolates of S. japonicum). The ITS1 is
      composed of 3 distinct regions: the 5' end (23 nucleotides); a tract of
      approximately 90-140 nucleotides, which occurs up to 7 times in tandem, the
      number varying even within an individual in all species investigated in this
      study; the 3' region (378 nucleotides), which lacks repeats. There is size and
      sequence variation among copies of the ITS1 repeat within a single individual.
      The relative abundances of size variants of ITS1 in S. japonicum have been
      ascertained by hybridizing genomic digests with an ITS1 probe. Multiple repeats
      and intra-individual variation in numbers and abundance of these is a feature of
      the Asian schistosomes, but not generally of African schistosomes. Possible
      reasons for this difference in ITS1 between African and Asian schistosomes are
      discussed. The ITS1 repeat sequences described for African schistosomes are
      different to, and cannot be aligned with, those from the Asian species described
      here, whereas the remainder of the ITS1 can be aligned quite easily.

PMID- 9585932
TI  - In vitro stimulation of metacyclogenesis in Leishmania braziliensis, L. donovani,
      L. major and L. mexicana.
AB  - Promastigotes of Leishmania braziliensis, L. donovani, L. major and L. mexicana
      recently derived from tissue amastigotes were cultured in Schneider's Drosophila
      medium supplemented with 20% (v/v) heat-inactivated foetal calf serum and 25
      micrograms gentamicin sulfate/ml at pH 5.5. These cultures produced more
      metacyclic promastigotes in their stationary-phase populations than others
      cultured at pH 7.0. Metacyclic promastigotes possessed a short (< or = 8 microns)
      and narrow (< or = 1.5 microns) cell body with a flagellum twice or more the
      length of the cell body. Promastigotes from acidic cultures were more resistant
      to complement-mediated lysis and more infective in vivo than those grown at
      neutral pH. These results demonstrate that induction of metacyclogenesis by
      acidic pH is a response conserved across a variety of species of Leishmania.

PMID- 9585934
TI  - The metalloprotease inhibitor 1,10-phenanthroline affects Schistosoma mansoni
      motor activity, egg laying and viability.
AB  - The Zn(2+)-chelating metalloprotease inhibitor 1,10-phenanthroline
      (phenanthroline, 5-150 microM) elicited dose-dependent contraction of the
      longitudinal and circular (transverse) musculature of adult male schistosomes. At
      the same concentrations, phenanthroline did not cause contraction of dispersed
      individual muscle fibres. The phenanthroline-induced contractions were reduced by
      the inclusion of 100 or 300 microM Zn2+ in the extracellular medium.
      Phenanthroline (0.5-150 microM) also inhibited the egg production of adult worm
      pairs in vitro, with a 98% reduction at 50 microM. When worm pairs were exposed
      to phenanthroline, the males detached from the dish and released the females,
      resulting in unpaired worms. At the higher concentrations (50 and 150 microM),
      the worms were killed in vitro. Worm burdens were reduced by over 50% in infected
      mice injected with phenanthroline (20 mg/kg/day for 4 days), but twice the dose
      resulted in only a 25% reduction. Phenanthroline injections also induced an
      hepatic shift and an unpairing of adult worms in infected mice, and the female
      worms appeared degenerate and lacked gut pigmentation. Mice fed a diet containing
      0.3% phenanthroline received significant protection from infection when
      challenged with schistosome cercaria, where phenanthroline-fed mice had 94% fewer
      adult worms than control mice. The broad range of phenanthroline effects on
      schistosomes suggests broad and important functions for metalloproteases in these
      worms.

PMID- 9585935
TI  - Onchocerca ochengi: assessment of the Simulium vectors in north Cameroon.
AB  - In the savanna areas of tropical Africa, cattle are frequently infected with the
      filaria Onchocerca ochengi. This parasite is closely related to Onchocerca
      volvulus, the causative agent of human onchocerciasis (river blindness), and is
      capable of developing in the same vector, Simulium damnosum s.l. In North
      Cameroon, where both O. ochengi and O. volvulus are endemic, we carried out a
      field study (reported in this and 2 following papers) to examine to which extent
      the transmission of the 2 parasite species overlap and what influence this has on
      the epidemiology of human onchocerciasis. In this paper we report our experiments
      to determine which of the S. damnosum species in North Cameroon act as vectors of
      O. ochengi, how efficiently they do so and whether other Simulium species play a
      vector role. To this end, infected cattle were exposed near 5 rivers in different
      geographical areas. Among 14 Simulium species identified as aquatic and/or adult
      stages at these rivers, only 6 (S. squamosum, S. damnosum s.s., S. sirbanum, S.
      bovis, S. wellmanni and S. hargreavesi) were found to bite cattle in important
      numbers in at least 1 of the sites. The 3 species of the S. damnosum complex were
      all capable of ingesting microfilariae (mf) of O. ochengi and developing a
      proportion of them to infective larvae (L3). Whereas S. squamosum and S. damnosum
      s.s., the prevailing vectors in the Guinea and Sudan savanna respectively, showed
      a high vector competence (17% of ingested mf developed to L3), S. sirbanum, which
      was much rarer in both areas, appeared to have a much lower susceptibility (2%).
      Other boophilic Simulium species were only seen in certain sites and seasons,
      being either incapable of ingesting important numbers of O. ochengi mf from body
      regions where these mf were abundant (S. bovis, S. hargreavesi); not able to
      support the development of ingested mf to L3 (S. wellmanni), or bit cattle
      preferentially in the ears, where O. ochengi mf do not occur (S. hargreavesi). We
      conclude that in North Cameroon members of the S. damnosum complex are the only
      important vectors of O. ochengi, with S. squamosum and S. damnosum s.s. being the
      main vectors.

PMID- 9585936
TI  - Onchocerca ochengi: morphological identification of the L3 in wild Simulium
      damnosum s.l., verified by DNA probes.
AB  - In order to assess the prevalence of the cattle filaria Onchocerca ochengi in
      onchocerciasis vectors (Simulium damnosum s.l.) in North Cameroon, we searched
      for a means to morphologically identify its developing larvae, which closely
      resemble those of O. volvulus. To this end microfilariae of the 2 Onchocerca
      species were isolated from slaughter cattle in Ngaoundere and injected into
      neonate Simulium species. Whereas the early developmental stages (sausage stage,
      L2 and pre-infective larva) were indistinguishable, the infective larvae (L3) of
      O. ochengi were longer (median: 740 microns), more slender (diameter = 19.3
      microns = 2.6% of body length) and had a relatively shorter tail (4.9% of body
      length) than those of O. volvulus (680 microns, 20.5 microns, 3.0% and 5.8%
      respectively). The tail of O. ochengi L3 was thick and rounded, whereas it was
      slightly tapering in O. volvulus L3. O. ochengi L3 produced by feeding flies on
      infected cattle in a different area in North Cameroon (Sora Mboum) showed the
      same features as intrathoracically produced O. ochengi L3 from Ngaoundere, but
      were even longer (785 microns). On the basis of the differences in length,
      relative diameter, length of the tail and shape of the tail, a simple key for the
      separation of O. volvulus and O. ochengi L3 was elaborated, and 248 L3 found in
      wild S. damnosum s.l. were separated into 'O. ochengi' (160 L3) and 'O. volvulus'
      (88 L3) following this key. Sequential dot blot hybridization of each of the 248
      larvae with a DNA probe which reacts with O. ochengi and O. volvulus but not with
      other Onchocerca species (pOo5/1) and with an O. volvulus-specific DNA probe
      (pOv12) revealed that the morphological identification had been correct in 86-91%
      of the cases. Only a small proportion (6-9%) of the dot blots did not react with
      either probe. Since this proportion was equal in experiments using experimentally
      produced L3 and in experiments using wild L3, the nonhybridization was certainly
      due to a loss of L3 during washing of the filters and not due to the presence of
      other unknown L3 species resembling O. volvulus and O. ochengi. Our study shows
      that in Cameroon it is possible to identify O. volvulus and O. ochengi infective
      larvae during routine fly dissections by morphology alone.

PMID- 9585937
TI  - Onchocerca ochengi: epidemiological evidence of cross-protection against
      Onchocerca volvulus in man.
AB  - In North Cameroon, the vector of Onchocerca volvulus (causative agent of human
      onchocerciasis) also transmits 2 filariae of animals: O. ochengi from cattle and
      O. ramachandrini from wart hogs. In order to assess the qualitative and
      quantitative roles of these 'animal filariae' in the epidemiology of O. volvulus,
      the transmission of the 3 parasites was measured in 2 villages and related to the
      endemicity of human onchocerciasis. In Galim, a cattle-farming Guinea savanna
      village where wild animals are rare, the overwhelming majority of all filarial
      infections found in the Simulium damnosum s.l. vectors throughout the year were
      O. ochengi (89%). The remaining infections were mainly O. volvulus (10.5%), and a
      few O. ramachandrini (0.5%). In Karna, a crop-farming Sudan savanna village where
      cattle are rare, but wild animals common, flies were also more frequently
      infected with animal filariae than with the human parasite. In the dry season,
      when nomadic cattle are present, 54% of all infections were O. ochengi, 36% O.
      volvulus and 10% O. ramachindrini. In the rainy season, when the cattle move
      away, flies were mainly infected with O. ramachandrini (52% of all infections)
      and secondly with O. volvulus (48%). In Karna, the relationship between the
      Annual Transmission Potential (ATP) of O. volvulus and its prevalence in the
      human population conformed to other onchocerciasis foci, in that a moderate ATP
      led to hyperendemic onchocerciasis. In Galim, however, a 7-fold higher O.
      volvulus-ATP (caused by a very high biting rate of the flies) contrasted with a
      strikingly low endemicity of onchocerciasis. Since, at the same time, in Galim
      the transmission of O. ochengi (measured on man) was very high (15,000 L3/fly
      collector/year), we hypothesize that the reduced endemicity of onchocerciasis in
      Galim is due to 'natural heterologous vaccination' by the large annual number of
      O. ochengi-L3, inoculated into man by anthropo-boophilic S. damnosum s.l. The
      importance of micro-epidemiology for the understanding of the interlinkage of
      human and animal onchocerciasis is discussed.

PMID- 9585938
TI  - Identification of a laminated layer-associated protein in Echinococcus
      multilocularis metacestodes.
AB  - Echinococcus multilocularis is a cestode parasite that predominantly infects red
      and arctic foxes as definitive hosts. Ingestion of E. multilocularis eggs and
      subsequent post-oncospheral infection with the larval stage (metacestode) of the
      parasite results in alveolar echinococcosis (AE), a life-threatening hepatic
      disease concerning humans and other intermediate hosts such as small rodents. The
      primary fluid-filled vesicles of the asexually proliferating metacestode are
      comprised of an inner germinal layer, a syncytial tegument, and an outer,
      acellular, so-called laminated layer. This laminated layer may play an important
      role in protecting the developing E. multilocularis metacestode from host immune
      reactions, and laminated layer-associated components represent potential targets
      for intervention during the course of AE. We have used an in vitro cultivation
      technique for the long-term maintenance and proliferation of E. multilocularis
      metacestodes in order to generate premature (protoscolex-free) parasite vesicles.
      A polyclonal antiserum was raised against this host-free parasite tissue.
      Subsequent immunoblot analysis of parasite fractions obtained by Triton X-114
      extraction lead to the identification of a 116 kDa protein (named EmP2) within
      the Triton-insoluble fraction. The characterization of EmP2 by SDS-PAGE, Western
      blotting, and by immunofluorescence revealed that EmP2 is a laminated layer
      associated protein.

PMID- 9585939
TI  - Ultrastructural investigation of the secondary excretory system in different
      stages of the procercoid of Triaenophorus nodulosus (Cestoda, Pseudophyllidea,
      Triaenophoridae).
AB  - The formation of the definitive procercoid excretory system of the
      pseudophyllidean cestode Triaenophorus nodulosus has been investigated. This
      process can be divided into 3 main stages. In the first stage, active autophagic
      processes lead to the formation of intracellular excretory canals. In the second
      stage, the process of the autolysis is enhanced and the system of intercellular
      lacunae functioning as an excretory system is formed. A definitive excretory
      system of the procercoid forms at the next stage, by means of the migration and
      proliferation of undifferentiated cells replacing the lacunar system.

PMID- 9585941
TI  - Comparative performance of species richness estimation methods.
AB  - In most real-world contexts the sampling effort needed to attain an accurate
      estimate of total species richness is excessive. Therefore, methods to estimate
      total species richness from incomplete collections need to be developed and
      tested. Using real and computer-simulated parasite data sets, the performances of
      9 species richness estimation methods were compared. For all data sets, each
      estimation method was used to calculate the projected species richness at
      increasing levels of sampling effort. The performance of each method was
      evaluated by calculating the bias and precision of its estimates against the
      known total species richness. Performance was evaluated with increasing sampling
      effort and across different model communities. For the real data sets, the Chao2
      and first-order jackknife estimators performed best. For the simulated data sets,
      the first-order jackknife estimator performed best at low sampling effort but,
      with increasing sampling effort, the bootstrap estimator outperformed all other
      estimators. Estimator performance increased with increasing species richness,
      aggregation level of individuals among samples and overall population size.
      Overall, the Chao2 and the first-order jackknife estimation methods performed
      best and should be used to control for the confounding effects of sampling effort
      in studies of parasite species richness. Potential uses of and practical problems
      with species richness estimation methods are discussed.

PMID- 9585940
TI  - Extracellular and cytoplasmic Cu/Zn superoxide dismutases from Haemonchus
      contortus.
AB  - Full-length cDNAs encoding cytosolic (SODc) and putative extracellular (SODe)
      Cu/Zn superoxide dismutases (SODs) from the ovine gastrointestinal parasitic
      nematode Haemonchus contortus have been isolated and characterized. The predicted
      sequences of the H. contortus SODs showed strong homology to other helminth SODs,
      the highest level of sequence similarity was with those of the free-living
      nematode Caenorhabditis elegans++. The predicted amino acid sequence of the
      putative extracellular form contained an N-terminal extension with the
      characteristics of a signal sequence including a potential signal peptidase
      cleavage site. Transcripts of both classes of Cu/Zn SOD were detected in all life
      cycle stages examined. The cytosolic SOD mRNA was approximately 6-fold more
      abundant than that of the extracellular enzyme in adult parasites. Immunoblotting
      with antisera raised to in vitro-expressed parasite SODs revealed the presence of
      2 proteins in extracts of adult H. contortus, with molecular masses of
      approximately 19.8 and 18 kDa. An additional protein of approximately 16.8 kDa
      was detected in adult ES material. Immunofluorescent staining showed Cu/Zn SOD
      was localized in the body wall musculature and the pharynx in adult worms and in
      the uterine tract of adult females. The immunogenic properties of recombinant H.
      contortus Cu/Zn SODs was assessed in a challenge infection experiment in lambs.

PMID- 9585942
TI  - [Transplantation of fetal dopaminergic cells simultaneously to the corpus
      striatum and pars reticularis of the substantia nigra in hemi-parkinsonian rats].
AB  - INTRODUCTION: Transplantation of foetal dopaminergic cells has been extensively
      used as restorative treatment for Parkinson's disease. OBJECTIVE: This study was
      carried out to determine the survival, modifications in rotatory activity induced
      by D-amphetamine and total content of dopamine in the striatal and nigra regions
      of hemiparkinsonian rats which had had foetal mesencephalic cells simultaneously
      transplanted to the striatum and pars reticularis of the substancia nigra.
      MATERIAL AND METHODS: The study was done using adult male Wistar rats weighing
      200-250 gms. The following experimental groups were formed, depending on the site
      of transplant: St: transplant to striatum (n = 2); SNr: transplant to SNr (n =
      20), ST + Snr; transplant to striatum and SNr simultaneously n = 20; and control
      (lesion with no transplant) n = 20. We studied the rotatory activity induced by D
      amphetamine 1, 2, 3 and 6 months after transplantation. After this time the rats
      were deeply anaesthetized and randomly allocated for morphological study or
      biochemical determination of the total dopamine content in the St and SNr using
      the HPLC technique. RESULTS: Study of conduct showed no significant differences
      in rotatory activity induced by D-amphetamine between the groups with
      intrastriatal transplants, but there was a difference between these and the SNr
      and control groups. Biochemical analysis showed that striatal DA content was
      significantly greater in the ST for the groups with intrastriatal transplants.
      The content of substancia nigra DA was significantly greater in the SNr of the ST
      + SNr group, followed by the ST group. Morphometric study showed differences,
      which were not significant, between ST transplanted animals and significant
      differences between the SNr transplanted group with a significant increase in
      survival of the SNr of the ST + SNr group. CONCLUSIONS: These results suggest a
      positive effect due to intrastriatal transplants compared to survival following
      intranigral transplants.

PMID- 9585943
TI  - [A study of lacunar infarcts based on analysis of the main anatomopathological
      series in the literature].
AB  - INTRODUCTION: There are few clinico-anatomopathological studies of lacunar
      infarcts (LI), because of the excellent functional prognosis and unlikelihood of
      death occurring whilst in hospital. MATERIAL AND METHODS: We reviewed the 10 main
      anatomopathological series of LI in the literature. A personal contribution was
      made based on analysis of the LI analyzed in 50 consecutive autopsies of patients
      with cerebrovascular disease. A descriptive clinico-anatomopathological
      assessment was done. Cerebrovascular risk factors, associated neurological
      syndromes and causes of death were analyzed. RESULTS: A total of 1,200 cases were
      analyzed in the 11 anatomopathological series. The most usual number of LI was
      between 2 and 5 per brain (6 series). The commonest topographical lesions found,
      in order of frequency, were: In the lenticular nucleus (9 series), thalamus (4
      series) and frontal white matter (4 series). The main risk factor was arterial
      hypertension (AHT), which occurred in between 58% and 90%. The main clinical
      findings were: Pseudobulbar syndrome (6 series), pure motor hemiparesia (3
      series) and clinically silent ischemia (2 series). The causes of death were
      mainly non-neurological and due to ischemic cardiopathy, sepsis and pulmonary
      embolism. CONCLUSIONS: LI are usually multiple, and topographically they are
      found at the level of the basal ganglia. AHT is the main cerebrovascular risk
      factor. The causes of death are usually non-neurological.

PMID- 9585944
TI  - [Prevalence and features of headache and migraine in childhood].
AB  - INTRODUCTION: A study of the prevalence of childhood cephalea has been carried
      on. MATERIAL AND METHODS: We studied a sample of children aged from 3 to 14 years
      old that consulted to different public health services clinics for control
      routine. We used an interview based in a questionnaire planned to be answered by
      parents and the child himself. RESULTS AND CONCLUSIONS: The more relevant results
      were: 1. Prevalence of cephalea 42%; 2. Prevalence of migraine according to
      Vahlquist and Kurtz criteria: 8.7% and 6.5% respectively (confidence intervals
      between 4.4% and 11.1%); 3. Higher proportion of girls for both cephalea and
      migraine; 4. Higher frequency of cephalea and the migraine type headache are
      facts related to the decision of seeking medical assistance; 5. 87% of children
      with migraine from the sample have relatives with intermittent cephalea; 6.
      Patients selected as having migraine, according to Vahlquist criteria, have the
      following predominant symptoms: Unilateral condition, vomiting/ nausea, improving
      with sleep, photophobia, phonophobia, changes in physical facial appearance, need
      to interrupt activities, pulsation quality, and visual aura.

PMID- 9585945
TI  - [Symptomatic West's syndrome: specific etiological link to unexpected response to
      treatment].
AB  - INTRODUCTION: It has been known that patients with symptomatic West Syndrome (WS)
      generally show poor responses to classic treatment, either steroids or
      antiepileptic drugs (AED). However new evidences arose in the last few years
      showing that particular association of WS with Down Syndrome (DS), type 1
      Neurofibromatosis (NF1) and cerebral palsy (CP) with periventricular leukomalacia
      (PL) tend to behave as cryptogenic or idiopathic cases showing control of
      infantile spasms (IS) and disappearance of hypsarrhythmia after treatment. The
      special case of vigabatrin as treatment for IS in babies with Tuberous Sclerosis
      is also an example. MATERIAL AND METHODS: We studied 15 patients with WS and DS
      with a follow-up of 1.5 to 9 years, 5 patients with WS and NF1 followed-up form 2
      to 6 years and 10 patients with WS associated with CP and PL followed-up during
      2.5 to 12 years. Seizures frequency, EEG and responses to treatment were
      evaluated. RESULTS: 1. WS and DS: IS had onset at a mean age of 6.5 months. No
      other type of seizures was registered. EEG showed typical hypsarrhythmia in 12
      cases and asymmetric hypsarrhythmia 3. IS disappeared and EEG were normalized
      after 15 days of treatment in 10 patients and after 6 months in other 4 patients.
      Three patients presented myoclonic seizures and one motor partial seizures during
      follow-up, all of them responding to AED. 2. WS and NF1: Onset of IS took place
      between 4 and 9 months of age. EEG were hypsarrhythmic in all 5 patients. Four of
      them were seizure free after usual steroids treatment and showed no relapse
      during follow-up. 3. WS and CP associated with PL: These were 9 males and 1
      female with IS starting at a mean age of 6.5 months, without history prior
      seizures. All EEG showed hypsarrhythmia. IS stopped and EEG became normal during
      the first month of treatment in 9 patients. In the other one the IS arrested with
      the use of vigabatrin 10 months after onset. CONCLUSIONS: Patients with these
      particular etiologies associated with WS do not behave as the usual symptomatic
      cases of WS in their response to classic treatment of IS. In fact the control of
      IS and normalization of EEG had been as good or better than in cases of
      cryptogenic WS. Care should them be taken not to generalized the usual concept
      about poor prognosis of WS in the so called symptomatic cases.

PMID- 9585946
TI  - [Treatment of sleep apnea syndrome with CPAP: compliance with treatment, its
      efficacy and secondary effects].
AB  - INTRODUCTION: Continuous positive pressure via the nose (nasal-CPAP) is the first
      line of treatment in the sleep apnea syndrome (SAS). Long term compliance with
      treatment is essential for success and this may depend on the relation of benefit
      to side-effects. OBJECTIVE: To study the improvement in symptoms of SAS patients
      treated with CPAP, side-effects and compliance with treatment. MATERIAL AND
      METHODS: In accordance with the objectives a 10 question questionnaire was given
      to 65 patients diagnosed as having SAS after polysomnographic studies (PSG) who
      were being treated with CPAP. RESULTS: Eighty per cent of the patients complied
      with the treatment prescribed and 82% of these considered it to be effective.
      Ninety per cent of the patients noticed improvement of 50% of their symptoms and
      48% noticed improvement of more than 80%. The daytime symptoms which showed most
      improvement were the feeling of tiredness on waking (94.1%) and of excessive
      somnolence during the day. The nocturnal symptoms which most improved were
      snoring and inability to breathe whilst asleep (100% and 95.1% respectively).
      Ninety per cent of the patients complained of a side-effect and/or problem with
      the equipment. The commonest complaints were related to nasal problems (dryness,
      congestion, rhinorrhea, etc), which affected 61.5%. The main complaint about the
      equipment was of the noise it made (46%). However, only 6% of the patients gave
      up the treatment because of side-effects. CONCLUSION: CPAP is an effective
      treatment which is well tolerated in spite of its drawbacks.

PMID- 9585947
TI  - [Response to prophylactic treatment of benign headache in children].
AB  - INTRODUCTION: Common childhood headaches seldom require prophylactic treatment
      which, nevertheless, is quite often unsatisfactory. OBJECTIVE: To study drug and
      non-drug related factors that may influence the therapeutic response. MATERIAL
      AND METHODS: A four-month follow-up study of all patients attended during a year
      at the neuropediatric, outpatient hospital-based clinic, with > or = 2 monthly
      migraine without aura attacks, > or = 10 tension-type headaches, or both types of
      headaches. Patients were randomized to be treated on an open basis, placebo
      controlled, with flunarizine or piracetam. Headache frequency was evaluated
      according to treatment and patients' basal characteristics. RESULTS: 98 patients
      studied (56 migraine without aura, 24 tension-type headache, 18 mixed). 33%
      dropped out; they were school underachievers more frequently than those that
      completed the protocol. Of those completing the protocol and treated with placebo
      as the first choice of therapy, 27% reported total remission of symptomatology;
      those not remitting with placebo were high achievers at school significatively
      more frequently. At the end of the trial, 43% of the initially randomized
      patients still complained of headaches, regardless of treatment, showing a
      seasonal relationship. CONCLUSIONS: Prophylaxis of benign childhood headaches is
      needed in less than half of those reporting a high headache frequency; school
      achievement should be taken into consideration as another clue to compliance and
      headache persistence. On a short-term basis only the seasonal influence and the
      placebo effect can be held responsible for amelioration of symptomatology.

PMID- 9585948
TI  - [Beta trace protein in the cerebrospinal fluid and serum in meningoencephalitis].
AB  - INTRODUCTION: beta-trace protein or D2 prostaglandin synthase is a dual
      functional protein. Its role and clinical value in cerebrospinal fluid is under
      study. MATERIAL AND METHODS: Seventy four pediatric patients suffering from viral
      meningoencephalitis and 7 with bacterial meningoencephalitis were studied. Sera
      and cerebrospinal fluid samples were taken. Albumin and beta-trace protein were
      quantified by immunodiffusion and nephelometry respectively. RESULTS: Increased
      cerebrospinal fluid beta-trace protein levels in comparison with normal value
      were observed. Nevertheless such expected increment was no possible seen in
      bacterial meningoencephalitis. CONCLUSIONS: beta-trace protein may contribute
      with the etiological diagnosis in meningoencephalitis.

PMID- 9585949
TI  - [Epilepsy and sleep apnea syndrome].
AB  - INTRODUCTION: The reciprocal influence between Epilepsy and Sleep Apnea Syndrome
      (SAS/OSAS) may aggravate the prognosis of both processes. Hypoxemia during sleep
      in patients with SAS and sleep fragmentation as a consequence of periodic apneas,
      that provokes a chronic sleep deprivation, could decrease the convulsive
      threshold in epileptic patients. MATERIAL AND METHODS: We have carried out a
      descriptive and retrospective study in 20 patients with epilepsy and SAS, of
      which EEG recordings, video-polysomnography (PSG) and nocturnal oximetry were
      available. RESULTS: 90% were males. 75% had partial epilepsies and 25%
      generalized. The mean duration of epilepsy was 14.5 years. The mean seizures
      frequency was one per month. 35% had nocturnal seizures, 15% diurnal and 50% of
      the patients had diurnal and nocturnal seizures. Other symptoms associated with
      seizures were: Snoring (100%), daytime sleepiness (70%), nocturnal respiratory
      pauses (30%), arterial hypertension (30%), overweight (25%) and morning headache
      (15%). The PSG showed epileptic interictal discharges in 95% of the cases, focal
      in 80%, and a disturbance of the sleep architecture, with a decreased sleep
      efficiency and continuity. The mean hypopnea-apnea index was 38. CONCLUSIONS: The
      association Epilepsy-SAS in adult patients affected of localized epilepsy, with
      risk factors for SAS (male gender, obesity, snoring, adverse effects of drugs)
      must be taken into account and a video-PSG-oximetric study is indicated to
      confirm it. It should be noted that anticonvulsant therapy could cause breathing
      dysfunction during sleep or aggravate a pre-existing or latent SAS. It be
      expected that the satisfactory treatment of SAS could improve the control of the
      seizures in these patients.

PMID- 9585950
TI  - [Evaluation study of the chronic headache questionnaire].
AB  - INTRODUCTION: Semi-structured questionnaires, based on clinical criteria are used
      in the diagnosis of headache, but none has been used to study the two commonest
      types of chronic headache. The first step, before clinical application, is to
      carry out a study of the questionnaire's validity and predictive value.
      OBJECTIVE: The objectives of our study were to evaluate the validity and
      determine the effectiveness of the ZZA questionnaire in the differential
      diagnosis between transformed migraine (TM) and chronic tension headache (CTH),
      in a specialist Neurology Clinic. MATERIAL AND METHODS: The ZZA questionnaire,
      elaborated by one of the investigators, was made up of 20 questions aimed at TM,
      CTH or the chronicity of the headache. An observer, who did not know the
      diagnosis, gave the questionnaire to patients who had previously been diagnosed
      by the head of the Headache Clinic as having TM or CTH. The process of validation
      of the questionnaire consisted in showing that it was reliable, with valid
      contents and valid criteria. RESULTS: On analysis of reliability, the items ZZA1,
      ZZA15, ZZA16 and ZZA18 gave the highest indices. The Cochran Q test showed lack
      of uniformity of replies. Only ZZA1, ZZA15 and ZZA18 were predictive items
      showing MT. None of the questions to show CTH were predictive. After final
      adjustment the definitive model was made up of ZZA1, ZZA15 and ZZA18.
      CONCLUSIONS: The proposed questionnaire was not found to be useful for
      differential diagnosis between TM and CTH. Only 3 of the 20 questions were
      accepted as having some degree of validity and effectiveness. Two of these 3
      questions, based on clinical impressions of the author, might well be included in
      the diagnostic criteria of TM.

PMID- 9585951
TI  - [Ocular myasthenia: clinical course and strategies for treatment].
AB  - INTRODUCTION: Ocular myasthenia gravis is a localized form of myasthenia in which
      only the extra-ocular muscles are clinically affected, namely the levator
      palpebrae superioris and orbicularis oculi. Two years after onset of the ocular
      condition, it became generalized in 44-53% of the patients. OBJECTIVE: 1. To
      describe the clinical features, diagnostic characteristics and clinical course of
      seven patients who fulfilled the criteria for diagnosis of ocular myasthenia and
      in whom the condition did not become generalized: 2. Review recent papers on
      this. Material and methods. We studied seven patients (two men and two women)
      diagnosed as having ocular myasthenia gravis, and followed them up for at least
      three years. RESULTS: The average age was 56.5. The clinical findings were of
      ptosis of the eyelids and diplopia. All seven patients were treated with
      pyridostigmine. In six cases prednisone was also given and in one patient
      thymectomy was done. There was a satisfactory result in all cases. CONCLUSIONS:
      The basic treatment of ocular myasthenia is with anticholinesterases and
      corticosteroids. Occasionally other immunosuppressives may be required.
      Prednisone seems to reduce the number of patients who go on to develop the
      generalized form.

PMID- 9585952
TI  - [Nerve compression syndrome in the thoracic outlet].
AB  - INTRODUCTION: The nerve conduction studies, F-waves and dermatosomal and lor
      somatosensory evoked potential have a low level of sensitivity for Thoracic
      Outlet Compression Syndrome (TOCS) diagnosis. A standard negative
      electrodiagnostic study does not exclude the presence of TOCS. OBJECTIVE: The
      purpose of this neurophysiological note is that the Wright's hyperabduction,
      costoclavicular compression and Adson's scalenus tests important in making a
      clinical diagnosis of TOCS can be used as neurophysiological provocative
      maneuvers to determine the effect of braquial position on electrodiagnostic
      parameters. MATERIAL AND METHODS: Nine selected TOCS patients were evaluated
      previous and following provocative maneuvers for 3 and 6 minutes. RESULTS: The
      results showed a positive electrodiagnostic study in 7/9 patients. CONCLUSIONS:
      It is suggested that patients with presumptive TOCS and negative
      electrodiagnostic findings be reevaluated immediately after 6 minutes of
      Wright's, Adson's or costoclavicular compression provocative tests.

PMID- 9585953
TI  - [Radial nerve lesions].
AB  - INTRODUCTION: The radial nerve is a prolongation of the posterior secondary trunk
      of the brachial plexous. It goes round the posterior aspect of the humerus, and
      is found anteriorly at the level of the forearm where it divides into two
      branches: 1. A deep motor branch, the posterior interosseus nerve; and 2. A
      superficial sensory branch, the superficial radial nerve. MATERIAL AND METHODS:
      Lesions of the radial nerve are studied by conduction tests (sensory and motor)
      and electromyography. Sensory manifestations of lesions of the radial nerve are
      usually limited to the dorso-lateral area of the hand. Motor disorders are
      usually seen as defects of extension, in which the triceps muscle may be involved
      depending on the level at which the lesion occurs. When topographical criteria
      are considered, the clinical syndromes of the radial nerve may be classified as:
      1. Neuropathies of the main trunk; 2. Neuropathies of the posterior interosseus
      nerve; and 3. Neuropathies of the superficial radial nerve. Trauma, external
      compression and trapping are the main causes of lesions in these syndromes.
      CONCLUSIONS: The radial nerve may be involved in multi-neuropathic processes
      forming part of a systemic illness (vasculitis, diabetes, etc.) or of a purely
      neuro-muscular disorder (acute neuropathy of the brachial plexus, neuropathy due
      to the effect of pressure and motor multifocal neuropathy.

PMID- 9585954
TI  - [Lateral femoral cutaneous neuropathy: paresthetic meralgia. Neurophysiological
      diagnosis].
AB  - INTRODUCTION: The neurophysiological approach to meralgia paresthetica (MP) deals
      with the possible abnormalities demonstrated in the peripheral nerve conduction
      and/or somatosensory evoked potentials (SEP) of the lateral femoral cutaneous
      nerve (LFCN). MATERIAL AND METHODS: To ascertain the diagnostic value of these
      methods, a group of 23 patients with unilateral MP symptoms has been studied; SEP
      of LFCN was also evaluated in a series of normal people. RESULTS: LFCN conduction
      was abnormal on the symptomatic side in 47.6% of the cases and nerve potential
      was absent on both sides in all the rest. SEPLFCN showed some impairment in 91%
      of the cases on the symptomatic side and responses were obtained on the
      asymptomatic side in every case; the most common abnormality was the delay of the
      response followed by its followed by its absence. In the normal group, the
      amplitude of potentials registered on the contralateral scalp to the stimulated
      side was usually higher than that registered on the median line, where they
      eventually lacked. Methodologically, this fact supports the need of a multiple
      recording of the SEPLFCN on the scalp. CONCLUSIONS: The SEPLFCN should be
      considered as the main technique for the objective diagnosis of MP and although
      LFCN conduction can supply useful information in individual cases, its exclusive
      use may lead to rather many positive false results.

PMID- 9585955
TI  - [Ambulatory monitoring of the EEG (A/EEG). Guidelines, methodology and
      indications].
AB  - INTRODUCTION: Ambulatory monitoring of EEG by means of a cassette recording
      (A/EEG) allows cerebral electrical activity or other biological signals to be
      recorded during long periods, not less than 24 hours, with the patient being free
      to move around in his usual surroundings or in the hospital. MATERIAL AND
      METHODS: The recordings are made using a system of electrodes, recording
      apparatus and software. CONCLUSIONS: The A/EEG is useful in the study of various
      diagnostic procedures, basically in the diagnosis and characterization of
      epilepsy. It is also useful in presurgical evaluation of patients with drug
      resistant epilepsy in whom surgical treatment is being considered. In these
      cases, the possibility of prolonged monitoring allows some of the patient's
      crises to be recorded, which is very useful in finding the site of the lesion. It
      is also useful when studying patients with hypersomnia or disorders of the
      wakefulness-sleep cycle. It is complementary to multiple sleep latency tests
      (TLSM) and polygraphic recordings of nocturnal sleep, since it allows the
      quantity, duration and type of sleep to be recorded during prolonged monitoring
      for more than 24 hours.

PMID- 9585956
TI  - [Ambulatory monitoring of A/EEG in the preoperative assessment of partial
      epilepsy].
AB  - INTRODUCTION: Electroencephalography, together with new neuroimaging techniques
      is still the main diagnostic tool for pre-operative assessment of epilepsy. The
      electrical episodes, both ictal and intercritical, are random paroxystic
      phenomena with regard to presentation, so the conventional EEG is sometimes of
      limited value. Therefore, in recent years, long duration EEG monitoring
      techniques have been favoured, with or without simultaneous recording of clinical
      behaviour, permitting recording for an indefinite period. Amongst these
      techniques, monitoring using cassette recording (A/EEG) if of specific interest
      since it permits the study of outpatients. OBJECTIVE: The main aim of surgical
      treatment of epilepsy is to abolish or reduce the number of crises. Therefore it
      is essential to localize the epileptogenic area as precisely as possible. The
      A/EEG has made a major contribution to the procedure of pre-operative assessment
      because of the considerable information it gives regarding the recording and
      character of the crises. MATERIAL AND METHODS: During the past three years,
      preoperative assessment has been carried out in our hospital on 44 patients with
      drug-resistant partial epilepsy. A total of 103 long duration cassette recordings
      (A/EEG) were done. Of these, 58 were done with surface electrodes and
      individualized set-up depending on the EEG findings, 8 with semi-invasive
      (sphenoid) electrodes, and 37 recordings used implanted sub-dural electrode
      strips. RESULTS: Combined study of the results obtained with these techniques
      permitted localization of the lesive-epileptogenic complex in 42 of these
      patients. We present the results obtained and conclude that A/EEG monitoring is
      useful in the pre-operative assessment of epilepsy.

PMID- 9585957
TI  - [Prolonged monitoring with video-EEG. Clinical applications].
AB  - INTRODUCTION: The differential diagnosis of paroxysmal events include a large
      number of entities. A careful diagnosis is needed because of the specific
      treatment that most of them require. If a mistake is done in the diagnosis, the
      consequences in the treatment may be relevant, not only because the maintenance
      of the episodes but because the secondary effects of the wrong medications. The
      video-EEG monitoring is key when the diagnosis of epileptic seizures is
      suspected. However, this is not the exclusive indication for a video-EEG
      monitoring study. CONCLUSIONS: Nowadays, epilepsy surgery is not considered
      without a previous monitoring study. In this article we review the indications
      for a video-EEG monitoring must be included as an usual system of diagnosis in a
      Neurophysiology Unit.

PMID- 9585958
TI  - [Neurophysiological evaluation of the pelvic floor].
AB  - INTRODUCTION: Methods for investigating the pelvic floor neurophysiological means
      are described. These include recording electromyographic activity of pelvic
      muscles and sphincter, under urodynamics studies or to assess the integrity of
      innervation of the muscle, pudendal and dorsal nerve of the penis conduction
      velocity, sacral reflexes and afferent and efferent conduction studies between
      the cortex and the pelvic floor, under our hospital protocol and a description of
      the major method from published reports and the clinical applications (Neurogenic
      bladder, faecal incontinence, male impotence) are discussed.

PMID- 9585959
TI  - [Image processing in the primary visual cortex].
AB  - INTRODUCTION: Area 17 or the primary visual area forms the first link in the
      chain of cerebral analysis of a visual image. The neurones forming the primary
      visual cortex are characterized by the extreme precision of their connections,
      functional specialization and hierarchic organization. The spatial precision of
      the connections within the system for vision permit retinotopic representation in
      the visual cortex, so that each point of the retina is projected into a specific
      area of the cortex. The cortical neurones which analyze the characteristics of
      the image situated in a precise zone of the visual field are themselves organized
      into a basic functional unit known as a hypercolumn. Within each hypercolumn
      there are various columnar cell systems with receptive fields having similar
      characteristics. Thus, each hypercolumn is made up of multiple orientation
      columns, two ocular dominance columns and 'blob' regions. All these systems
      permit the analysis of different aspects of the image. The neurones belonging to
      the orientation columns are sensitive to the orientation, spatial frequency and
      movement of a visual stimulus; those of the 'blob' regions to colour, and the
      binocular neurones of the ocular dominance columns to depth. Within each column,
      the hierarchical pattern of neurone interconnections determines the successive
      appearance of cells with receptive fields having new properties.

PMID- 9585960
TI  - [Electroretinogram: technique and clinical applications].
AB  - INTRODUCTION: The retina is a neuronal membrane that covers the posterior part of
      the eye chamber and is formed by several layers. The retinal function can be
      synthesize as the light translation into nervous impulses in the optic nerve.
      MATERIAL AND METHODS: The ERG is the expression of the changes of the electrical
      potential in the retina after a luminous stimulus. There are different types of
      retinal stimulators specially flash, ganzfeld and pattern which are the most used
      in the clinical neurophysiological explorations. RESULTS: We expose the obtained
      responses, the morphology, amplitude and latencies of the (a) and (b) waves in
      scotopic and photopic conditions with ganzfeld or flash stimulator. In the ERG
      pattern we describe the waves for the transitory ERGP as well as for the Steady
      State ERGP. We refer to the protocols proposed by the International Society of
      Electrophysiology of Vision (ISCEV). We mention the clinical applications of
      these techniques and we give our personal experience in diseases such retinitis
      pigmentosa, maculopathies, retinal degenerations, vascular diseases, cataracts
      and traumatic lesions of the retina.

PMID- 9585961
TI  - [P300 potentials evoked by visual stimulation].
AB  - INTRODUCTION: The P300 potential is a long-latency endogenous component of the
      event-related potentials to low-probability target stimuli. The same stimulus
      delivered without cognitive process does not provoke endogenous components;
      moreover event-related potentials are not dependent of the sensory pathways used
      for stimulating the subjects. P300 potential is a biological parameter used in
      scientific investigations in Clinical Neurophysiology, Neurology,
      Psychophysiology and Psychiatry. The most frequent methodology for obtaining P300
      event-related potential is based on the 'odd-ball' paradigm using auditory
      stimulation. In this revision we analyzed the difficulties of this methodology
      and we propose to use the visual stimulation in order to obtain well defined P300
      potential, based on a better signal to noise ratio and minor overlapping of
      exogenous and endogenous components of the evoked potentials. The improvement in
      the quality of the results obtained when comparing with auditory stimulation, it
      is supposed to facilitate that the use of P300 potential overflows the field of
      the investigation and permits their extensive use in the clinical practice.

PMID- 9585962
TI  - [Visual evoked potentials (VEP). Current perspectives].
AB  - INTRODUCTION: The objective of this study is to describe current tendencies in
      the recording and interpretation of visual evoked potentials (VEP). In the
      introduction we describe the history of the three main classical schools and the
      modern methodology which combines them, so as to study the photopic and scotopic
      systems together and thus be better able to determine the origin of the
      underlying pathology. MATERIAL AND METHODS: We describe recording techniques
      using flash and chequer-board and a strategy for study of the visual pathway.
      RESULTS: The application of this technique is described for pathologies in which
      its findings are of particular interest: Silent multiple sclerosis, Parkinson,
      hepatic encephalopathy, dementia and psychiatric disorders in which certain
      neurotransmitters play a part; visual acuity; coma and brain death; cortical
      blindness. A separate section deals with paediatrics, in view of its special
      characteristics. We call for a return to the use of this technique with great
      future diagnostic potential.

PMID- 9585963
TI  - [Visual evoked potentials and electroretinogram in pediatrics. Concept
      methodology and clinical applications].
AB  - INTRODUCTION: Since the first visual evoked potentials were obtained in the early
      1940s, many important technical advances have been developed helping to produce
      more correct responses. One of the most important has been the incorporation of
      computers in the 1960s. This allowed the improvement in the relation signal/noise
      and consequently the responses are much more reliables technically. Also the
      improvement in the stimulators and electrodes necessaries for this test. However,
      all this advances introduced the use of the physical and technical concepts and
      magnitudes that sometimes fall outside the strict field of the medicine. MATERIAL
      AND METHODS: Therefore we have divided this work into three very different parts.
      The first part is dedicated to remembering and defining a series of physical
      concepts and their usefulness in the obtention of VEPs and ERGs specially in the
      physical process witch the proper use are basic to attain correct responses. In
      the second part we will discuss VEPs and ERGs in pediatric patients under the age
      of two years., concentrating basically on the every day specific problems witch
      appear on treating young patients. Finally we will review briefly their most
      frequent clinical applications.

PMID- 9585964
TI  - [Sleep as behavior].
AB  - INTRODUCTION: Throughout life human beings maintain an alternating rhythm of two
      biological rhythms between three states: wakefulness, NREM sleep and REM sleep.
      These states are quite distinct both with regard to conduct and physiologically.
      Sleep is an active process during which an amalgam of behavioural and
      physiological processes occur, together with complex cerebral activity. The
      universality of sleep or similar resting behaviour in the animal kingdom has
      encouraged study of its origin and function. The phylogenetics of sleep and the
      study of behaviour during this state in different species of animals offers ample
      possibilities to understand its significance. We describe the characteristics of
      conduct which define the different phases of sleep in adult humans. Motor
      activity, relationship with the surroundings, perception of and reaction to
      external stimuli, ability to recognize and remember are all variables which are
      modified during the transition from wakefulness to sleep, NREM sleep and REM
      sleep. Changes in behaviour during sleep form a group of pathological conditions
      with different origins and physiopathological methods involved. The parasomnias
      are the alterations of behaviour during sleep par excellence. We describe the
      concept and classification according to current theories.

PMID- 9585965
TI  - [Alertness disorders and parasomnias of the wakefulness-sleep transition].
AB  - INTRODUCTION: Disorders of arousal and parasomnias of sleep-wake transition are
      revisited. Disorders of arousal are: Sleepwalking (SW), confusional arousals (CA)
      and sleep terrors (ST). SW, CA and ST are different clinical manifestations of
      the same disorder being ST the most severe and SW the mildest manifestation.
      Disorders of arousal are typical parasomnias of NREM sleep, mainly slow wave
      sleep. Pathophysiological mechanism of these disorders is the state's
      dissociation of wakefulness and sleep. The conjunction of the constitutional
      factors (genetic, age, sleep privation, drugs, psychological, etc.), and
      precipitant factors (light, sound, temperature, touch, apnea, gastroesophageal
      reflux, seizure, fever, psychological, etc.) permit three possible arousal
      behavioral response: A full awakening, a shift stage of sleep or a partial
      arousal. Clinical significance of arousal parasomnias depend on the age. In
      children are caused by developmental and genetic factors and usually are
      autolimited. In adults usually are caused by psychopathology. In the elderly are
      often caused by organic brain syndromes. Parasomnias of sleep-wake transition
      are: Rhythmic movements of sleep, sleeptalking, starts and the nocturnal cramp.
      Most of them are mild disorders, almost physiological phenomena that usually
      don't need any treatment.

PMID- 9585966
TI  - [Parasomnias linked to the REM phase].
AB  - INTRODUCTION: The different parasomnias normally associated to REM sleep and
      included in the International Classification of Sleep Disorders (ICSD-90), are
      described. Clinical characteristics allow to do diagnostic of all of them, but
      the ones that allow an exact differential diagnostic over other parasomnias and
      other types of behavioral alterations, are the data obtained in sleep laboratory,
      with different polisomnographic and synchronized videotape techniques. Special
      emphasis is made in REM sleep behavior disorder.

PMID- 9585967
TI  - [Parasomnias in infants below one-year old of age].
AB  - INTRODUCTION: Certain sleep disorders which occur in children and adults show the
      same phenomena, although presentation, significance, cause and treatment are all
      different. However, there are some disorders which are only found in infancy, as
      in the four conditions which we review below. In spite of great variation between
      individuals, the general way in which the wakefulness-sleep states mature during
      the first months of life is well known. In general the physiological patterns of
      REM and NREM are in general the same in children as in adults. However, the
      pathological patterns are similar, but there are major differences between them.
      These differences are mainly physiological, behavioural, parent-child
      relationship and specific disorders. We shall see that the central alveolar
      hypoventilation syndrome of infants is not the same as that of adults. The sleep
      apnea syndrome of the newborn is different to the apneas seen in older children.
      Benign neonatal myoclonia of sleep are not present in adults, and finally the
      sudden death of an infant is not like the unexplained nocturnal sudden death or
      sinus arrest linked to paradoxical sleep in adults.

PMID- 9585968
TI  - [Differential diagnosis of parasomnias and epilepsy].

PMID- 9585969
TI  - A new approach to oligonucleotide synthesis in solution.
AB  - A new approach to the synthesis of oligonucleotides and their phosphorothioate
      analogues in solution has been developed; it is based on H-phosphonate coupling
      and in situ sulfur-transfer.

PMID- 9585970
TI  - A highly efficient synthesis of cyclaradine and its behaviour towards adenosine
      deaminase.
AB  - (+)-, (-)-, and (+/-)-Cyclaradines were efficiently synthesized from 2-aza
      bicyclo[2.2.1]hept-5-en-3-one (ABH). (+)- and (+/-)-Cyclaradines were deaminated
      by adenosine deaminase whereas (-)-cyclaradine was not hydrolyzed under the same
      conditions.

PMID- 9585971
TI  - Synthesis of novel dioxane nucleosides having two bases, physico-chemical
      properties, and their biological activities.
AB  - Novel dioxane nucleosides having two bases, 2(R)-(5-fluorouracil-1-yl)-5(R)
      hydroxymethyl-3(R)-(uracil-1-yl)-1,4-dioxane (7a) and 2(S)-(5-fluorouracil-1-yl)
      5(R)-hydroxymethyl-3(R)-(uracil-1-yl)-1,4-dioxane (7b) were synthesized from
      uridine to develop a new category of nucleoside for therapeutic use. Some
      derivative of precursors of the nucleoside were also synthesized and several
      compounds synthesized were tested antitumor activity using human gastric cancer
      cell lines in culture.

PMID- 9585972
TI  - Synthesis of bis-netropsin-linked hydroxamic acids and their DNA cleavage
      properties in the presence of transition or lanthanide metal ions.
AB  - Nobel hydroxamic acids containing bis-netropsin units coupled by
      polymethylenetether (BNHA) have been synthesized. BNHA-ferrous complexes sequence
      specifically cleaved pBR322 DNA fragment whereas corresponding cerium complexes
      showed low-sequence specific cleavage pattern.

PMID- 9585973
TI  - Specific interaction between 5'-aminonucleosides and borates and influence of
      borates on nucleoside conformations.
AB  - The unique conformation and orientational change of 5'-amino-5'-deoxyuridine in
      Kolthoff's buffer is discussed. From CD and NOE spectra, anomalous syn
      orientation of Urd-5'-NH2 might be caused by specific interaction between borates
      and Urd-5'-NH2, which promote the formation of hydrogen bonding between 2
      carbonyl oxygen and hydrogen of 5'-amino group. This borates induced syn
      orientation of Urd-5'-NH2 could be applied to external stimulation control of
      target RNA/DNA hybridization.

PMID- 9585974
TI  - Synthesis of DHPA analogs and their inhibitory activities of human recombinant S
      adenosyl-L-homocysteine hydrolase.
AB  - We report syntheses of DHPA analogs, e.g., 9-(3-formyl-2,3
      dihydroxypropyl)adenine (FDHPA) and 9-(3-formyl-2,3-dihydroxypropyl)hypoxanthine
      (FDHPI). Among these DHPA analogs, FDHPA behaved as an irreversible inactivator
      of human recombinant SAH hydrolase.

PMID- 9585975
TI  - Synthesis of echiguanine analogs and their ribofuranosyl glycosides that inhibit
      phosphatidylinositol 4-kinase.
AB  - N-carboxamide-substituted 7-deazaguanine-7-carboxamides and their ribofuranosyl
      compounds have been synthesized as phosphatidylinositol (PI) 4-kinase inhibitors.
      The ethylamide derivative and the corresponding ribofuranosyl compound inhibited
      PI 4-kinase with IC50 values of 0.02 and 2.4 micrograms/ml, respectively.

PMID- 9585977
TI  - Synthesis of the 2'-deoxy-2'-fluoro and 3'-deoxy-3'-fluoro analogues of 8
      bromoadenosine.
AB  - After protection of the two sugar hydroxyl groups of 8-bromoadenosine, the
      products were converted to the arabinoside or xyloside, which were treated with
      diethy laminosulfur trifluoride (DAST) and acid to afford 2'-deoxy-2'-fluoro- or
      3'-deoxy-3'-fluoro-8-bromoadenosine. 8-OH and 8-SH derivatives were obtained from
      8-bromo congener.

PMID- 9585976
TI  - Intramolecular oxyselenation of (5'S)-C-(4-phenyl-1,3-butadienyl)uridine:
      synthesis of octosyl nucleosides.
AB  - (5'S)-C-(4-Phenyl-1,3-butadienyl)uridine (8) was prepared from the (5'S)-C-styryl
      derivative 2. Intramolecular oxyselenation of 8 proceeded in a 6-endo-trig manner
      to yield the cyclized product 9. Compound 9, having appropriate substituents at
      the 5'-, 6'-, and 7'-positions, was found to serve as a key intermediate for the
      synthesis of octosyl nucleosides.

PMID- 9585978
TI  - Chemical synthesis of H-phosphonate DNA without using N-protecting groups.
AB  - Oligodeoxyribonucleotides were synthesized by using N-unprotected H-phosphonate
      monomers. It was found that the amino groups of nucleosides were not modified
      during condensation where benzotriazolyloxy carbonium and phosphonium types of
      compounds were employed as condensing reagents. The most effective condensing
      reagent for rapid internucleotidic bond formation was found to be 2-(benzotriazol
      1-yloxy)-1,1-dimethyl-2-(pyrrolidin-1- yl)-1,3,2- diazaphospholidinium
      hexafluorophosphate (BOMP). In the present H-phosphonate approach, 2
      benzenesulfonyl-3-(3-nitrophenyl)oxaziridine (BNO) was successfully employed as a
      new oxidizing reagent for oxidation of the H-phosphonate linkages under anhydrous
      conditions.

PMID- 9585979
TI  - Imidazolium triflate as an efficient promoter for O-selective phosphitylation of
      N-unprotected nucleosides via the phosphoramidite approach.
AB  - A novel method for the preparation of nucleotides via the phosphoramidite
      approach with imidazolium triflate 1 as a promoter has been developed. This
      approach required no protecting groups for nucleoside bases of building blocks.

PMID- 9585980
TI  - Synthesis and incorporation of tricyclic-imidazo[5',4':4,5]pyrido[2,3
      d]pyrimidine nucleosides into oligonucleotides and their thermal stability.
AB  - We designed and synthesized four novel tricyclicnucleosides 1-4, which have
      imidazo[5',4':4,5]pyrido[2,3-d]pyrimidine structures, to construct
      theramallystable, non-natural, DNA duplexes. Both 1:2 and 3:4 possess four
      complementary hydrogen-bond pairs and are expected to form more stable base-pairs
      than the naturally occurring Watson-Crick base-pairs when incorporated into
      oligodeoxynucleotides (ODNs). NMR studies of these base-pairs at the nucleoside
      level in CDCl3 identified the expected base-pair formation with four hydrogen
      bonds. We also synthesized several ODNs containing these nucleosides and measured
      their thermal stability. We found that if several of the novel base-pairs were
      incorporated on complementary strands, the resulting DNA duplexes had very high
      thermal stability.

PMID- 9585981
TI  - Isopoly-L-ornithine derivative as nucleic acid model.
AB  - Isopoly-L-ornithine derivatives of thymine, and thymidine were found to hardly
      interact with poly A. Conformational studies of the oligomers with CD and NMR
      revealed that stable intramolecular hydrogen bonding was formed between the
      thymine base and the ornithine unit.

PMID- 9585982
TI  - Studies on the mechanism of DNA sequence selective alkylation by kapurimycin A3
      analogs.
AB  - We synthesized kapurimycin A3 ABCD-ring analog and compared the sequence
      selectivity for DNA guanine alkylation with those of kapurimycin A3 and ABC-ring
      analog. In the binding to DNA, it was shown by DNA unwinding assay that ABCD-ring
      analog binds tightly to DNA by intercalation into DNA duplex. DNA alkylation by
      ABCD-ring analog was sequence selective with an order of G*G > G*A > G*T > G*C.
      ABCD-ring analog has a stronger binding ability, a higher reactivity to DNA and a
      higher GG sequence selectivity in DNA alkylation than those to ABC-ring analog.
      The aromatic ring system plays an important role in the effective GG selective
      alkylation.

PMID- 9585983
TI  - Synthesis of oligodeoxyribonucleotide containing novel C-5 reactive 2'
      deoxyuridine derivative and its functional modification via post-synthetic
      technique.
AB  - 2'-Deoxyuridine derivatives bearing an activated ester at C-5 position were
      synthesized and was examined their use for the preparation of modified
      oligodeoxyribonucleotides (ODNs) by a post-modification method. The ODNs
      containing cyanomethyl ester at C-5 position of the deoxyuridine residue reacted
      easily with a primary amine of several functional molecules under the mild
      condition to give the corresponding modified ODNs.

PMID- 9585984
TI  - A spectrometric method for determining the capability of intermolecular
      interaction: mono- and dideoxynucleotides.
AB  - A method for detecting the dimer of mono- and oligodeoxynucleotides is presented
      by using fast atom bombardment mass spectrometry (FAB-MS). The mass spectrum of a
      mononucleotide dpC showed an intense peak of the dimeric ion dpC:::dpC, compared
      with those of dpA, dpG and dpT. The mass spectrum of an equimolar mixture of dpC
      and dpG showed the highest peak of the dimeric ion dpC:::dpG, compared with all
      other combinations. The dimeric ion peaks in the mass spectra of dinucleotides
      d(ApT) and d(CpG) were relatively high and it may reflect the base-pairing energy
      due to hydrogen bonding. The degradation patterns of each dimers for d(ApT) and
      d(CpG) obtained by using the collision-induced dissociation (CID) technique which
      reflected the strength of each base-pairing.

PMID- 9585985
TI  - Synthesis and evaluation of oligonucleotides incorporating novel artificial
      nucleobases for the selective formation of non-natural type triplexes.
AB  - Regulation of specific gene expression by the sequence specific triplex formation
      has been expected as a new biological tool or a new therapeutic method in the so
      called antigene strategy. As native nucleobases form triplexes only within
      homopurine-homopyrimidine duplexes, expansion of the target sequences to general
      ones has been desired. We have previously reported the selective formation of
      base triplets by the non-native nucleobases (1, 2) with a CG or a TA base pair,
      respectively, in the organic solvent. In this paper, we wish to report the
      synthesis of the new non-native bases (3, 4, 9-11) and their incorporation into
      the triplex-forming oligonucleotides (TFOs), as well as their ability of triplex
      formation.

PMID- 9585986
TI  - Synthesis of stereoselectively 5'-monodeuterated nucleoside with defined S/R
      ratios. An application to the assignment of 5'-methylene signals of DNA
      oligomers.
AB  - A method to prepare 5'-monodeuterated nucleosides with various S/R-ratios is
      described. 5-Oxopentose derivatives synthesized from glucose were converted into
      5-monodeuterated pentose derivatives by LiAID4 in the presence of various
      ligands. The stereoselectivities of the deuteration reactions were investigated
      under a variety of conditions, and the S/R-ratios of the 5-monodeuterated
      pentoses varied from 4 : 1 to 1 : 7.4. By mixing these 5-monodeuterated pentose
      derivatives, we have successfully synthesized thymidine with a defined S/R-ratio
      at C5'.

PMID- 9585987
TI  - Raman scattering tensors of adenine.
AB  - Polarized Raman scattering measurements have been made of a single crystal of
      adenine dihydrochloride (adenine-2H+) by the use of Raman microscope with 488.0
      nm excitation. The adenine-2H+ crystal belongs to the space group Pnma
      (orthorhombic), and Raman intensities of Iaa, Ibb, Icc and Iac (which correspond
      to the aa, bb, cc and ac components of the crystal Raman tensor) have been
      determined for each Raman band. The depolarization ratios of Raman bands have
      been observed for fully random molecular orientations in an adenine 6N HCl
      aqueous solution. From these experimental data, and by taking the known crystal
      structure into account, anisotropic and isotropic molecular Raman scattering
      tensors have been determined for each vibrational mode of the adenine residue.

PMID- 9585988
TI  - Analysis of guanine oxidation product via electron transfer in 5'-d(TTGGTA)-3'.
AB  - The photoirradiation of 5'-TTGGTA-3' in the presence of riboflavin with or
      without complementary oligomer 5'-ATACCAAA-3' was investigated by HPLC analysis.
      It was found that 2-aminoimidazol-4-one (Iz) containing hexamers, 5'-TTIzGTA-3'
      and 5'-TTGIzTA-3', were the major products.

PMID- 9585989
TI  - Michael addition reactions of some nucleobases to 1-(4,6-O-benzylidene-2,3
      didehydro-2,3-dideoxy-3-nitro-beta-D- hexopyran osyl) uracil.
AB  - Michael addition of cytosine, N4-dimethyl-aminomethylidene-cytosine, uracil and
      thymine to the nitroolefin (2) generated in situ from 1-(4,6-O-benzylidene-3
      deoxy-3-nitro-beta-D-glucopyranosyl)-uracil (1) gave the corresponding 2-(N1
      pyrimidinyl)-2,3-dideoxy-3-nitro-beta-D-glucopyranosides (3-6). Compound 3 was
      also obtainable from 4.

PMID- 9585990
TI  - Synthesis of 2'-deoxy-2'-fluoro-4'-thioarabinonucleosides using the Pummerer
      rearrangement and their biological evaluation.
AB  - Searching for more effective antineoplastic and antiviral agents, we have
      prepared various 2'-deoxy-2'-fluoro-4'-thioarabinonucleosides. The glycosylation
      reaction of persilylated pyrimidine bases with a 4-thiosugar derivative was
      performed using SnCl4 as a catalyst. The same reaction between purines and the 4
      thiosugar, catalyzed by TMSOTf, gave the corresponding purine 4'-thionucleosides.
      Pyrimidine derivatives (e.g., 5-ethyluracil, 5-iodouracil, and 5-iodocytosine)
      showed potent anti-HSV-1 activities, and guanine and 2,6-diaminopurine
      derivatives showed marked anti-HCMV activities.

PMID- 9585991
TI  - Oligonucleotide synthesis by the use of a 2-(levulinyloxymethyl)-5-nitrobenzoyl
      (LMNBZ) group for the 5'-hydroxyl group of ribonucleoside and 2'
      deoxyribonucleoside 3'-phosphoramidites.
AB  - Synthetic studies on the CpCpA terminus triplet, whose exocyclic amino groups are
      all labeled with 15N, and a phosphorodithioate-linked oligonucleotide in terms of
      2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) group as the novel base-labile
      protecting group for the 5'-hydroxyl groups of nucleoside 3'-phosphoramidites,
      are described.

PMID- 9585992
TI  - Highly diastereoselective synthesis of 2'-deoxy[2'-2H]ribonucleoside derivatives
      by the use of tris(trimethylsilyl)[2H]silane.
AB  - The use of (Me3Si)3SiH or (Me3Si)3Si2H-Et3B system in place of Bu3SnH or Bu3Sn2H
      Et3B system for a reductive protylation or deuteration reaction of 2'-Br-2'-deoxy
      3',5'-O-TIPDS-[2'-2H]ribonucleosides or 2'-Br-2'-deoxy-3',5'-O-TIPDS
      ribonucleosides was confirmed to improve the reactions to afford an excellent
      diastereoselectivity, i.e., the diastereoselectivity of (2'S)- or (2'R)-2'-deoxy
      [2'-2H]ribonucleosides obtained by the reaction at 0 degree C is equivalent to
      the diastereoselectivity obtained by that using Bu3SnH or Bu3Sn2H-Et3B system at
      < -70 degrees C; the reductive deuteration of 2'-O-phenoxythiocarbonyl-3',5'-O
      TIPDS-ribonucleosides through (Me3Si)3Si2H-Et3B system at 0 degree C also gave
      (2'R)-2'-deoxy[2'-2H]ribonucleosides with such a high diastereo-selectivity as
      above.

PMID- 9585993
TI  - Synthesis of 5'-deoxy-5'-substituted pyrimidine nucleosides employing
      intramolecular glycosylation.
AB  - 5'-Deoxy-5'-arylthio and 5'-azido pyrimidine nucleosides were synthesized
      employing intramolecular glycosylation, in which a reaction intermediate was
      treated in situ with thiol and an azide salt, respectively.

PMID- 9585994
TI  - Structure of DNA containing aristeromycin analog.
AB  - The melting temperatures and thermodynamic properties of several
      oligodeoxynucleotide duplexes containing one modified deoxyadenosine residue
      (carbocyclic deoxyadenosine, dAr) were investigated. It was found that the
      introduction of carbocyclic deoxyadenosine slightly destabilized oligonucleotide
      duplexes mainly due to an entropic contribution.

PMID- 9585995
TI  - Preparation of thietane derivatives from 2-(3-hydroxyalkylthio)benzoxazoles and
      their conversion into thietane nucleosides.
AB  - Thietanes were prepared by the reaction of 2-(3-hydroxyalkylthio)benzoxazoles
      with KH. 3,3-Dibenzylthietane was oxidized by mCPBA to give 3,3-dibenzylthietane
      1-oxide, which was converted into thietane nucleosides (Pummerer-type-reaction).

PMID- 9585996
TI  - Synthesis of cyclodeca-1,5-diyne derivatives having o-nitrophenylseleno group.
AB  - 7-Benzoyloxy-3-(2-nitrophenylseleno)-1,5-cyclodecadiyne (13) was prepared from 5
      hexyn-1-ol and propargyl bromide via 10-iodo-7-(t-butyldiphenylsiloxy)-5,9
      decadiynal (10). The facile cyclization of the acyclic precursor 10 would be
      rationalized in terms of "bulky group (TBDPSO) assisted conformational control".
      Oxidation of 13 by NaIO4, followed by thermal treatment gave
      tetrahydronaphthalene derivative 15, indicating the generation of biradical.

PMID- 9585997
TI  - Stereocontrolled cyclization at the anomeric position of 6-(hydroxyalkyl)uridines
      using hypoiodite reaction.
AB  - Hypoiodite reaction of 6-(hydroxyalkyl)-2',3'-O-isopropylideneuridines (1-3) was
      found to yield a new class of spiro nucleosides having an anomeric orthoester
      structure. It appeared that the 6-hydroxyalkyl substituent and the 2',3'-O
      isopropylidene group are working cooperatively to control the anomeric
      stereochemistry (beta/alpha = 35/1-2/1) of the cyclization.

PMID- 9585998
TI  - Synthesis of 6-aminouracils and pyrrolo[2,3-d]pyrimidine-2,4-diones and their
      inhibitory effect on thymidine phosphorylase.
AB  - Inhibitors of thymidine phosphorylase (dThdPase) are expected to suppress the
      growth and metastasis of tumor cells by inhibition of angiogenesis and were
      designed by utilizing the three dimensional structure of the enzyme. 5
      Substituted 6-aminouracils (5) and 7-substituted pyrrolo[2,3-d]pyrimidine-2,4
      diones (6) were synthesized and tested for inhibition of human placenta thymidine
      phosphorylase. 5-Bromo-6-aminouracil (5d), 5-cyano-6-[3-(methylamino)propyl]
      uracil (5e), and 7-(2-aminoethyl)-pyrrolo[2,3-d]pyrimidine-2,4-dione (6c)
      inhibited dThdPase with IC50s of 7.6, 3.8 and 44.0 microM, respectively.

PMID- 9586000
TI  - Synthesis of nucleosides having unusual branched sugars as potential antiviral
      agents.
AB  - Enantiomerically pure novel nucleosides having unusual branched sugars were
      synthesized in a stereospecific manner from a common chiral pool of (S, S)-1,4
      bis(benzyloxy)-2,3-epoxybutane and evaluated for antiviral activity.

PMID- 9585999
TI  - Asymmetric synthesis of 4'-alpha-alkylcarbovir derivatives.
AB  - Asymmetric synthesis of 4'-alpha-alkylcarbovir derivatives 3 were achieved based
      on Sakai's asymmetric alkylation of beta-keto esters. The key carbocyclic
      intermediate 12 was synthesized from 6 via an eleven-step sequence. Coupling of
      12 with 2-amino-6-chloropurine followed by desilylation and subsequent hydrolysis
      gave the target compounds 3 in moderate yields.

PMID- 9586001
TI  - Synthesis and properties of carbocyclic oligothymidylate lacking the 5'
      methylene.
AB  - Oligodeoxynucleotides possessing a shortened internucleotidic linkage have been
      prepared using carbocyclic nucleosides lacking the 5'-methylene as the monomeric
      units. Specifically, the oligomers derived from carbocyclic 5'-n or thymidine and
      2'-hydroxy-3'-deoxythymidine will be described.

PMID- 9586002
TI  - Novel cross-linking reaction of oligonucleotides incorporating new base analogs
      with selective reactivity toward cytidine.
AB  - 2-Amino-6-vinylpurine analog (1) has been proven to react with cytidine and
      guanosine in a model reaction of cross-linking. However, its incorporation into
      the ODNs was unsuccessful because of the high reactivity of its vinyl group. A
      new precursor for 1, 2-amino-6-[2-(phenylthio)ethyl]purine (2), was designed so
      as to generate the reactive vinyl group after introduction into the oligomers. In
      this paper, synthesis of ODN containing 2, easy generation of the vinyl group
      within the oligomer, and interstrand cross-linking between the ODN incorporating
      1 and the target DNA, are described.

PMID- 9586003
TI  - Synthesis and properties of oligonucleotide derivatives containing a hydrophobic
      fluorescent dye at the 2'-position.
AB  - The oligonucleotides containing 2'-(6-dimethylamino-2-naphthamide)uridine
      [U(DAN)] at the different position were synthesized by the fully automated solid
      phase phosphoramidite methods. The UV melting profiles for the U(DAN)-modified
      oligonucleotides with complementary DNA exhibited sigmoidal curves whose shapes
      were similar to those for the unmodified duplexes.

PMID- 9586005
TI  - Synthesis of stereoselectively 13C/2H-doubly labeled DNA oligomers by the
      combined use of chemical and enzymatic reactions.
AB  - (2'S,5'S)-(1',2',3',4',5'-13C5;2',5'-2H2-thymidine, prepared via labeled ribosyl
      thymidine as described in the accompanying paper, has been successfully converted
      into isotopically labeled dA, dG, and dC using enzymatic transdeoxyribosylation
      reactions.

PMID- 9586004
TI  - Preparation of DNA-peptide conjugate using oxime resin.
AB  - In order to prepare oligonucleotide-peptide conjugate molecules bearing
      additional functions, such as cellular membrane permeability, nuclease
      resistance, which are indispensable to antisense and triplex oligonucleotides for
      their practical use in vivo, it is found that application of oxime resin (Kaiser
      resin) to automated DNA synthesis and succeeding cleavage of DNA fragment bound
      to oxime resin by various nucleophiles, such as amines, alkoxides and protected
      peptides, give DNA conjugate molecules conventionally in moderate to good yields.

PMID- 9586006
TI  - Selective multiple labeling strategy to obtain accurate NMR parameters for
      nucleic acids. Conformational analysis around the glycosidic bond.
AB  - A systematic synthesis of pyrimidine nucleosides with 13C-labels only at specific
      atoms in both the base and sugar moieties has been developed in order to obtain
      conformational information about the glycosidic bond through measurement of the
      accurate vicinal coupling constants between H1' and C2/C6. For this purpose, 13C
      labels at three positions, namely C1', C2, and C6, are essential. We have
      synthesized selectively multiply labeled nucleosides, such as [2, 1'-13C2]
      thymidine, [2, 1'-13C2]-2'-deoxycytidine, [6, 1'-13C2]-thymidine, and [6, 1'
      13C2]-2'-deoxycytidine. These nucleosides will be useful to determine the
      relative orientation of the base and sugar moieties.

PMID- 9586007
TI  - Solid phase synthesis of U1 RNA oligomers containing a TMG cap structure.
AB  - We report the solid-phase synthesis of a 5'-terminal part of U1 RNA. In this
      approach, a new method for pyro- and tri-phosphate bond formation on solid
      supports was studied. Since 2,2,7-trimethyl guanosine (TMG) in the cap structure
      was unstable under basic conditions, a RNA oligomer was synthesized by using a
      linker having the P-N bond, which can be cleaved from the solid support by
      treatment with 80% acetic acid.

PMID- 9586008
TI  - Non-intercalative and sequence selective interaction between four intercalative
      reagents and dinucleotides.
AB  - The analysis of binding experiments between dextran coupled intercalators and
      nucleotides showed the base- and sequence-selective affinity to mono- and
      dinucleotides in aqueous solution. Acridine bound CH-Sepharose 4B also revealed
      base- and sequence-selective affinity.

PMID- 9586009
TI  - Mechanistic studies on the neighboring base damage induced by KMnO4 oxidation of
      8-oxoguanine in DNA.
AB  - New types of DNA substrates containing an 8-oxoguanine residue (8-oxo-G) were
      prepared in order to examine the mechanisms for the neighboring base damage
      initiated by KMnO4 oxidation of the 8-oxo-G. The results obtained from the
      reactions suggested that the damage at remote sites in the single strands can be
      explained by an electronic interaction (redox reaction) between an oxidized 8-oxo
      G species and the base (to be damaged), which are close each other in a loop
      structure. For the inefficient damage observed in duplex substrates, electron
      transfer through stacked bases might be involved.

PMID- 9586010
TI  - Optimal configuration of pyrene excimer induced by the excimer-forming two-probe
      nucleic acid hybridization method.
AB  - Excimer-forming two-probe nucleic acid hybridization (ETPH) method with pyrene as
      a fluorophore enables homogeneous hybridization assays. We examined the effect of
      linker length between a pyrene residue and a terminal sugar moiety on Tm of
      hybrids in the presence of 20% dimethylformamide (DMF). The results including
      those of CD measurements indicated no interaction of pyrene residues with the
      duplex formed between a target 32-mer and a pyrenemethyliodoacetamide-introduced
      16-mer probe (PMIA-P5)/a pyrenebutanoic acid-introduced 16-mer probe (PBuA-P3),
      which is the best pair of probes for intense excimer emission. This was also
      supported by a computer-assisted molecular modeling using Insight II and Discover
      software.

PMID- 9586011
TI  - Photoinduced cleavage of single and double stranded DNA at single guanine
      proximal to target sequence by dibenzoyldiazomethane-ODN conjugate.
AB  - DBDM-ODN conjugates selectively cleaved single and double stranded DNA at a
      specific guanine residue proximal to the target sequence upon exposure to 366 nm
      light.

PMID- 9586012
TI  - -GG- specific cleavage via hole hopping through double-stranded DNA.
AB  - We examined the photoinduced DNA cleavage reaction of 32P-end labeled
      oligodeoxyribonucleotides which contain 5'-TGGGC-3', 5'-CGGGC-3', and 5'-TGGGT
      3'. As for 5'-TGGGC-3' and 5'-TGGGT-3', the cleavage occurred most strongly at
      the middle of 5'-GGG-3' step, whereas the strongest cleavage occurred at the 5'
      side of 5'-GGG-3' in 5'-CGGGC-3' step. These results showed the 5' side base of
      5'-GGG-3' step was very important for the sequence selectivity of 5'-GGG-3'
      cleavage.

PMID- 9586013
TI  - Mechanistic investigation of photoreduction of 5-bromouracil-containing
      oligomers.
AB  - It was found that photoreduction of 5-bromouracil (BrU) occurs at 5'-ATBrU-3'
      sequence more efficiently than 5'-ABrU-3'. We introduced 5'-GG-3' sequence at the
      5'-side of 5'-ATBrU-3' sequence and 5'-ABrU-3' sequence and investigated their
      photoreduction. As a result, dIz, an oxidation product originated from guanine
      cation radical, was detected.

PMID- 9586014
TI  - Cooperative alkylation by duocarmycin A-distamycin A heterodimer.
AB  - Duo A (Duo) normally alkylates adenine N3 at the 3' end of A + T-rich sequence in
      DNA. The addition of another minor groove binder, dist A (Dist), dramatically
      modulate the site of DNA alkylation by Duo with great acceleration of the
      reaction rate. In order to examine the mode of alkylation, the kinetics of the
      reaction under various conditions were examined. Based on the simulation of
      experimental data, a new reaction pathway was proposed.

PMID- 9586015
TI  - Photoreaction of 5-halouracil-containing Z-form DNA.
AB  - Photoreactions of IU-containing Z-form DNA were investigated. By introducing 8
      methylguanine, stable Z-form IU-containing oligonucleotides were prepared. DNA
      conformational change from B to Z leads to the remarkable acceleration of the
      photoreactivity of IU-containing oligonucleotides. In particular 2'-hydrogen
      abstraction was observed preferentially in Z-form DNA, and 2'-hydroxylation
      occurred specifically at the 5' side of IU in Z-form DNA.

PMID- 9586016
TI  - Raman scattering tensors of 5-iodouracil.
AB  - Polarized Raman scattering measurements have been made of a single crystal of 5
      iodouracil by the use of a Raman microscope with the 488.0 nm excitation. The
      crystal belongs to space group P2(1) (monoclinic), and Raman scattering
      intensities, corresponding to the a'a', bb, cc, a'b and bc components of the
      crystalline Raman tensor, have been determined for each prominent Raman band,
      where a' is the axis perpendicular to the c axis in the ac plane. From these
      experimental results, the shapes and orientations of the Raman scattering tensors
      have been derived for 6 base vibrations in the 5-iodouracil molecule. By
      comparing these tensors with those for thymine and pseudouridine vibrations,
      discussions were made of the polarizability oscillations caused by the normal
      vibrations localized in the pyrimidine base.

PMID- 9586017
TI  - X-ray analysis of DNA dodecamer containing 2'-deoxy-N6-methoxyadenosine.
AB  - Oxyamines have been known as a mutagen which attacks amino groups of DNA bases.
      It is expected that the modified adenine derivative has a tautomer which can form
      a stable base pair not only with thymine but also with cytosine. For establishing
      such tautomerization mutagenesis, we have solved a crystal structure of DNA
      dodecamer containing 2'-deoxy-N6-methoxyadenosine. It is shown that the N6
      methoxyadenine takes a imino form to form a Watson-Crick type pairing with
      cytosine in the DNA duplex.

PMID- 9586018
TI  - Interaction of nitrosyl Fe(II) complex of bleomycin with DNA.
AB  - ESR spectra of Fe(III)BLM and NO-Fe(II)BLM on highly oriented DNA-fibers
      indicated that not only the iron binding domain of the BLM but also the
      orientation of NO bond axis is fixed with respect to the DNA-double helical axis
      at room temperature.

PMID- 9586019
TI  - Fluorescence properties of quinacrine enantiomers complexed with synthetic double
      stranded polyribonucleotides.
AB  - The interaction of quinacrine (QAC) enantiomers with poly(A).poly(U) and
      poly(I).poly(C) has been studied by fluorescence spectroscopy. The fluorescence
      and fluorescence-excitation spectra of QAC enantiomers complexed with the
      polyribonucleotides showed a marked dependence on the excitation and emission
      wavelengths. This behavior of the bound QAC enantiomers was almost independent of
      the chirality of the cationic side chain and was very similar to that of the
      bound racemic QAC.

PMID- 9586020
TI  - The structures of nucleic acids composed exclusively of non-standard base pairs.
AB  - We have reported that d(GGAGGAA) forms a new type of quadruplex in the presence
      of K+. Here we report that in the absence of K+ it forms another kind of new
      structure composed of non-standard base pairs exclusively. The structure is
      neither a quadruplex nor a hairpin. The structure gives three clear imino proton
      signals of G at 10.0, 13.0 and 13.8 ppm, indicating the formation of G:A and/or
      G:G base pairs. The two signals at 13.0 and 13.8 ppm indicate that there are two
      base pairs in which the imino protons of G are hydrogen bonded. All residues take
      anti conformation, which imposes the restriction on the combination of a mutual
      direction of strands and types of base pairs. Phosphorus signals of the second
      and fifth residues appear at higher field, while that of the seventh residue at
      lower field, when compared with those of A and B form structures, suggesting
      deviations of a backbone conformation from the standard one. Replacement of the
      second or fifth G by I results in destabilization of the structure, which implies
      the involvement of amino groups of these residues in base pairing. On the basis
      of these results, the structure of d(GGAGGAA) is discussed.

PMID- 9586021
TI  - Hydrophobic effect of alkyl substituents on DNA intercalation of a dye.
AB  - Naphthalene imides carrying alkyl chains of different length were synthesized to
      evaluate the hydrophobic effect on DNA interaction with small molecules. These
      dyes bind to DNA with moderately high affinity of 10(4)-10(5) M-1 and raise the
      melting temperature of the DNA duplex by 8-18 degrees C at a 0.2 molar ratio of
      dye to DNA-p (phosphate unit). However, both the DNA binding affinity and DNA
      duplex stability decrease with an increase in the hydrophobicity (logP) of the
      dye. These results demonstrate that the interaction of the hydrophobic alkyl
      chain of the dye with the DNA groove destabilizes the DNA structure, presumably
      by removing the structure-stabilizing water from the DNA groove.

PMID- 9586022
TI  - Three-dimensional structural analysis of avian-teratogenic pyrimidine dialkyl
      phosphate esters and their analogs by molecular orbital calculations.
AB  - The most stable structures of avian-teratogenic pyrimidinyl dialkyl phosphates
      and phosphorothionates at semi-empirical molecular orbital (MO) AM1 method level
      were obtained to get net charges of nitrogen (N) and phosphorus (P), distances
      between 1-N and P, and twist angles between plane of the heterocycle and that
      made by C-O-P. These geometries of typical compounds were optimized by ab initio
      MO calculations at level of HF/6-31 G*. In the most potent teratogens, distances
      between 1-N and P were 4.3-5.4 A. Compounds of about 3 A has no teratogenicity.

PMID- 9586023
TI  - Molecular cloning of the gene encoding a 2Fe-2S ferredoxin from extremely
      halophilic archaeon Haloarcula japonica strain TR-1.
AB  - A ferredoxin was purified from extremely halophilic archaeon Haloarcula japonica
      strain TR-1, and then characterized. The Ha. japonica ferredoxin proved to
      contain a 2Fe-2S cluster. A part of the gene encoding the ferredoxin was
      amplified by PCR. Subsequently, the entire ferredoxin gene was cloned from
      chromosomal DNA of Ha. japonica using the PCR product as a probe. The structural
      gene consisted of an open reading frame of 387 nucleotides. The deduced amino
      acid sequence showed 89-98% identities with those of the ferredoxins from other
      extremely halophilic archaea.

PMID- 9586024
TI  - Primary structure of the novel bacterial rhodopsin from extremely halophilic
      archaeon Haloarcula japonica strain TR-1.
AB  - A novel bacterial rhodopsin was identified in Haloarcula japonica strain TR-1.
      The gene encoding the bacterial rhodopsin was cloned and sequenced. The
      structural gene consisted of an open reading frame of 750 nucleotides encoding
      250 amino acids. The deduced amino acid sequence of the Ha. japonica bacterial
      rhodopsin showed the highest homology to those of cruxrhodopsins.

PMID- 9586025
TI  - Sequence specific homogeneous detection of HCV RNA by fluorescence monitoring of
      in vitro transcription with intercalator-linked oligonucleotide probe.

PMID- 9586026
TI  - Codon reading properties of tRNA variants substituted within the anticodon loop.
AB  - Effects of base substitution within tRNA anticodon loop on the codon reading
      activities were quantitatively analyzed with the use of a set of unmodified tRNA
      molecules with GGA anticodon. The first (position 32) and the last (position 38)
      nucleotides of the anticodon loop of the wild-type molecule was changed from
      C32A38 to U32A38, U32G38, and C32G38. The codon reading activities of these
      variants relative to that of the wild type molecule were measured in a cell-free
      translation system. The reading of both the UCU and UCC codons were lower in all
      the three variants than in the wild-type molecule.

PMID- 9586027
TI  - Codon recognition by artificial tRNA molecules with modified nucleosides in the
      anticodon.
AB  - Proteins with unnatural amino acids at specific positions can be produced through
      cell-free protein synthesis. The synthesis of such molecules can, in principle,
      be facilitated by improving the codon reading efficiency of the tRNA that inserts
      the unnatural amino acid. In the present study, we prepared tRNA molecules with
      2'-O-methyl nucleosides at the second and third positions of the anticodon and
      measured their codon-reading efficiencies. The results indicated, contrary to our
      expectation, that the modification damaged the decoding function completely.

PMID- 9586028
TI  - Expression of GCF protein is dependent on the cell cycle.
AB  - GCF is reported to be a transcriptional regulator that binds to specific GC-rich
      sequences in the epidermal growth factor (EGF) receptor gene promotor and to
      represses its transcription. In this study, to examine the expression of GCF in
      cell cycle, we have developed antibodies against GCF protein. The anti-GCF
      antibody recognized a major band with a molecular weight of approximately 100 kda
      present in human Hela cell line by immunoprecipitation followed by Western
      blotting. Although GCF proteins were detected throughout the cell cycle, it
      reached the highest level in G1 phase, and fell down to the lowest level during
      G2/M phase. Thus, the expression of GCF is regulated in a cell cycle-dependent
      manner, suggesting a potential role of GCF in the control of cell growth.

PMID- 9586029
TI  - Re-examination of 5' end of cDNA of transcription factor GCF.
AB  - N-terminal region of transcriptional factor GCF was re-examined as the published
      amino acid sequence is extremely basic. 5'Rapid Amplification of cDNA End (5'
      RACE) analysis was performed and the result revealed that sequence of the first
      308 bases of published GCF cDNA does not conform to the one obtained by 5' RACE.
      Sequence of genomic GCF DNA is consistent with the new cDNA sequence but not with
      the published one. Results of ordinal RT-PCR analyses are consistent with that of
      5' RACE.

PMID- 9586030
TI  - Recognition of tRNA(Gly) by three widely diverged glycyl-tRNA synthetases:
      evolution of tRNA recognition.
AB  - Glycyl-tRNA synthetase (GlyRS) is an unusual aminoacyl-tRNA synthetase because it
      varies in its quarternary structure between organisms; Escherichia coli GlyRS is
      an alpha 2 beta 2 tetramer, whereas those of Thermus thermophilus and yeast are
      alpha 2 dimers. In contrast, the tRNA(Gly) sequence is virtually identical in E.
      coli and T. thermophilus but very different in yeast. In this study, we examined
      the molecular recognition of tRNA(Gly) by three widely diverged GlyRSs using in
      vitro tRNA transcripts. The results obtained in the mutation studies indicate
      that despite such large differences of the two prokaryotic GlyRSs, tRNA(Gly)
      identity has been essentially conserved in prokaryotes, and that there are also
      differences in the acceptor stem recognition between prokaryotes and yeast. The
      clear separation between prokaryotes and yeast is retained in the identity
      element location, whereas the apparent diversity of the two prokaryotic enzymes
      does not reflect on the tRNA recognition.

PMID- 9586031
TI  - Use of biotinylated-cysteinyl-tRNA as a non-RI probe in protein synthesis.
AB  - A convenient method for the preparation of biotinylated aminoacyl-tRNA to use in
      the non-radioisotopic (non-RI) detection of cell-free translation products was
      developed. After aminoacylation of E. coli tRNA(Cys) with L-cystein, its
      sulfhydryl group was modified with N-(6-[Biotinamide]hexyl)-3'-(2'-pyridyl
      dithio) propionamide or 1-Biotin amido-4-(4'-[maleimidomethyl] cyclohexane
      carboxamido) butane. These biotin-labelled cysteinyl-tRNA are expected to
      function as the non-RI probe for protein synthesis equally to or even better than
      the biotinylated lysyl-tRNA which is now commercially available.

PMID- 9586032
TI  - Deoxyribonuclease secreted from an insectivorous plant Drosera adelae.
AB  - A deoxyribonuclease that is secreted from an insectivorous plant Drosera adelae
      was partially purified by column chromatography. The enzyme acted as an
      endonuclease on double-stranded DNA and generated oligonucleotides with 3'
      hydroxyl and 5' phosphate ends. The activity of the enzyme was high in the range
      from pH 3.5 to 5.0. The enzyme seemed to require divalent cations for maximum
      activity.

PMID- 9586033
TI  - Quadruplex formation of oligonucleotides containing G clusters and their nuclease
      resistance.
AB  - Oligoribonucleotides containing four G clusters, (UGnU)4 (n = 3-5), were
      synthesized and characterized by electrophoretic analysis and resistance to
      nucleases. Electrophoretic analyses indicate that the oligomers except for
      (UG3U)4 can form antiparallel-stranded monomeric quadruplexes in the presence of
      potassium cation. The oligomers used in this study are protected from
      endonuclease P1 and venom phosphodiesterase degradation. In addition, the
      oligomers indicate resistance to nucleases in human serum and E. coli S-100
      fraction.

PMID- 9586034
TI  - Mechanism of substrate recognition by the ribotoxin, alpha-sarcin.
AB  - The substrate recognition and catalytic mechanisms of alpha-sarcin were explored
      with kinetic method by using synthetic 25-mer RNA mimicking the alpha
      sarcin/ricin loop in 23S rRNA of E. coli ribosomes. The oligomer containing deoxy
      G at the site of alpha-sarcin (G14) was a potent competitive inhibitor. The RNA
      having deoxy-G8 however, increases the Kcat value by about five times but without
      significant alteration on Km. Surprisingly, the deletion of G8 makes the oligomer
      become a strong noncompetitive inhibitor of the enzyme. These results suggested
      that there are at least two sites in the RNA substrate which are recognized by
      alpha-sarcin, one is the G8 bulge or at around its neighbor and the other is the
      GAGA in the sarcin/ricin loop of the rRNA.

PMID- 9586035
TI  - Role of the CCA end of tRNA and its vicinity in aminoacylation.
AB  - The CCA sequence is common to all the 3' ends of tRNAs and more than half of the
      tRNAs possess the G1C72 base pair at the end of acceptor stem. To study the role
      of these terminal trinucleotides and their vicinity in the aminoacylation
      process, not only the substitutions of these bases but also the nucleotide
      additions at the 5' end of tRNA were introduced into many kinds of Escherichia
      coli tRNA transcripts and the effects on the aminoacylation activity with cognate
      aminoacyl-tRNA synthetase were investigated. Basically the requirement of the CCA
      sequence in aminoacylation differed among each amino acid specific tRNA. Some
      rough conclusions could be drawn from the present results. It was found that the
      G1C72 base pair functioned as the negative identity elements in many tRNAs. The
      nucleotide-addition experiments suggested that proper spatial arrangement and
      flexibility were important for aminoacylation reaction. Functional and
      evolutional implications of the invariant CCA sequence and its vicinity were
      discussed.

PMID- 9586036
TI  - The molecular mechanisms of 5-fluoro-2'-deoxyuridine induced cell death.
AB  - The molecular mechanism of cell death induced by 5-Fluoro-2'-deoxyuridine (FUdR)
      was investigated. FUdR caused cell death to induce dNTP pool imbalance and
      following DNA double strand breaks in mouse mammary tumor FM3A cells. We isolated
      a new endonuclease from FUdR-treated cells, named endonuclease S, that played an
      important role in FUdR-induced cell death. Cells treated with FUdR showed
      intracellular acidification before cell death formation. We observed that the
      endonuclease S in acidic cells may lead the DNA fragmentation. On the other hand,
      we observed that protease inhibitors (such as TLCK, TPCK, PMSF, p-APMSF, Pefabloc
      SC and Z-Asp-CH2-DCB) blocked intracellular acidification, DNA fragmentation and
      FUdR-induced cell death. But the inhibitors did not affect dNTP pool imbalance in
      the cells. These results suggest that proteases act at the point of downstream of
      dNTP pool imbalance and upstream of the intracellular acidification.

PMID- 9586037
TI  - Cytotoxic mechanisms of new antitumor nucleoside analogues, 3'-ethynylcytidine
      (ECyd) and 3'-ethynyluridine (EUrd).
AB  - The cytotoxic mechanisms of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine
      (ECyd) and 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) were studied
      with mouse mammary tumor FM3A cells and human fibrosarcoma HT1080 cells. ECyd and
      EUrd are converted to ECyd 5'-triphosphate (ECTP) in the cells. ECTP has also
      outstanding stability in the cells; the half life of ECTP in FM3A cells was more
      than 3 days. The metabolisms and mechanisms of these analogues may play a key
      role in a potent antitumor activities against slow-growing solid tumors.

PMID- 9586038
TI  - Preparation of DNA-chitosan columns and their applications: binding of
      carcinogens to the column.
AB  - DNA, either native or denatured, can be immobilized by complexing with chitosan.
      The DNA-chitosan, which is insoluble in aqueous media, contains DNA at about 50%
      in weight. The DNA in the complex is accessible by enzymes and reagents.
      Carcinogenic heterocyclic amines, having affinity to DNA, can be adsorbed to the
      DNA-chitosan. The DNA-chitosan complex can be homogeneously dispersed in celite
      powder, and the resultant DNA-chitosan-celite is a material suitable to construct
      an immobilized DNA-column. The column was shown to be effective in concentrating
      heterocyclic amines.

PMID- 9586039
TI  - Molecular mechanism of the alternative expression of the Chlorella virus CVK2
      chitosanase gene.
AB  - A novel viral strategy for expression of two mRNAs from a single gene yielding
      two products with seemingly different functions (alternative gene expression) has
      be found. The vChta-1 gene of Chlorella virus CVK2 produced two functional
      chitosanase proteins with apparently different roles in viral infection: The
      larger 65-kDa chitosanase assembled into virion and presumably function at the
      beginning of infection, while the smaller 37-kDa enzyme remains in the host
      cytoplasm where it most likely aids in the digestion of the host cell wall prior
      to viral release. These predicted activities are essential for a cycle of viral
      infection. The dual expression of the vChta-1 gene most likely occurred by read
      through into a downstream gene, ORF245.

PMID- 9586040
TI  - Designing of plant artificial chromosome (PAC) by using the Chlorella smallest
      chromosome as a model system.
AB  - As a model for plant-type chromosomes, we have been characterizing molecular
      organization of the Chlorella vulgaris C-169 chromosome I. To identify chromosome
      structural elements including the centromeric region and replication origins, we
      constructed a chromosome I specific cosmid library and aligned each cosmid clones
      to generate contigs. So far, more than 80% of the entire chromosome I has been
      covered. A complete clonal physical reconstitution of chromosome I provides
      information on the structure and genomic organization of plant genome. We propose
      our strategy to construct an artificial chromosome by assembling the functional
      chromosome structural elements identified on Chrorella chromosome I.

PMID- 9586041
TI  - Conformational change of DNA on the formation of DNA-anti-DNA antibody immune
      complex.
AB  - Monoclonal antibodies were purified from the culture medium of hybridoma from
      systemic lupus erythematosus (SLE)-prone MRL/Mp-Ipr-Ipr mice with affinity
      chromatography. Binding activity of the antibodies to double-stranded DNA from
      salmon milt was actually shown in enzyme-linked immunosorbent assay (ELISA).
      Circular dichroism (CD) spectrum of DNA solution (150 mM NaCl, 20 mM Na2HPO4, pH
      7.4) which showed B-type conformation, changed significantly by addition of the
      anti-DNA antibodies. These results indicate that conformational change of DNA
      occurred by binding of anti-DNA antibodies, forming DNA-anti-DNA antibody immune
      complex.

PMID- 9586043
TI  - Parallel-stranded duplexes and quartet assemblies formed by oligonucleotides
      containing isoguanine.
AB  - Oligonucleotides with isoguanine-cytosine base pairs form duplexes with parallel
      chain orientation. This strong base pair dictates the strand polarity when
      additional dA-dT or N7Ad-dT pairs are present. The same is observed for the
      isocytosine-guanine pair. Quartet structures are built by the self-assembly of
      oligonucleotides containing short runs of isoguanine or 7-deazaisoguanine. New
      base pairs between isoguanine or guanine and 5-aza-7-deazaguanine are presented.

PMID- 9586042
TI  - Experimental quantitation of cation effect on nucleic acid stability.
AB  - Cation effect on DNA/DNA, RNA/RNA, and RNA/DNA stabilities was investigated
      quantitatively. Plots of predicted delta G degree 37 values vs. measured delta G
      degree 37 ones showed the same relationship for DNA/DNA, RNA/RNA, and RNA/DNA.
      The number of sodium ion concerned in a double helix formation was estimated, and
      the result indicated that the number of bound sodium ion may determine the duplex
      stability regardless of DNA/DNA, RNA/RNA, and RNA/DNA. Since these duplex
      stability can be predicted with the nearest-neighbor model, it is considered that
      the number of bound sodium ions is affected by the nearest-neighbor bases. The
      importance of the screening effect of the electrostatic repulsion by bound
      cations was also indicated for determining the duplex stability as well as the
      hydrogen bonding and stacking interactions.

PMID- 9586044
TI  - Different contributions of three zinc fingers of transcription factor Sp1 to DNA
      recognition: novel binding mode of N-terminal finger 1.
AB  - To clarify binding properties of the first zinc finger of Sp1, finger 1, to GC
      box DNA, two-finger mutant peptides Sp1 (zf12) and Sp1 (zf23) were created and
      their DNA binding characteristics have been compared with those of native three
      zinc finger protein Sp1. Some gel electrophoretic experiments involving DNase I
      footprinting and gel mobility shift assays reveal that finger 1 is not essential
      to sequence-specific DNA recognition, but moderately contributes to total binding
      affinity and overall sequence specificity by three zinc fingers of Sp1.

PMID- 9586045
TI  - New multi zinc finger protein: biosynthetic design and characteristics of DNA
      recognition.
AB  - New six zinc finger protein DSp1 was created by connecting two Sp1 DNA binding
      domains. The DNA recognition characteristics of DSp1 demonstrate that (1) this
      multi finger protein binds eighteen contiguous base pairs of DNA sequence, (2)
      each zinc finger wraps around DNA major groove, and (3) two Sp1 domains have
      nonequivalent contribution to the DNA binding of DSp1.

PMID- 9586046
TI  - Preliminary investigation of tRNA modification enzymes with Se in bovine liver.
AB  - We measured the amount of Se in the tRNA fractions eluted from a BD-cellulose
      column. Se was found in the fraction eluted early from the column as to be 3 x
      10(-4) mol/mol of tRNA. This low amount suggests that there is no tRNA species
      that contain 1 mol of Se per 1 mol of tRNA and only few specific tRNAs contain Se
      nucleotides. Next, we searched the Se modification enzymes with this tRNA
      fraction and found the activity in cytosol. Now the digestions of the tRNA
      modified with 75Se was analyzed by two dimensional TLC. tRNA(Sec) of T7
      transcript was not substrate for this enzyme.

PMID- 9586047
TI  - Construction of a novel conjugative plasmid harboring a GFP reporter gene and its
      introduction into animal cells by transfection and trans-kingdom conjugation.
AB  - We have established a novel method of gene introduction into eukaryotic cells by
      trans-kingdom conjugation between Escherichia coli/Agrobacterium tumefaciens
      bacteria and yeasts. To expand this to animal cells, we have constructed a novel
      conjugative plasmid, pBASGreen which contains SV40-ori/promoter, pUC-ori, IncQ
      type oriT/mob, Apr and Neor genes with GFP (green fluorescent protein) gene as a
      reporter. The introduction into COS1 and NIH3T3 animal cultured cells by
      conventional transfection was easily detected by fluorescence of the GFP gene
      product under a fluorescent microscope and the transfectants were effectively
      selected by the Neor marker. By the action of oriT/mob in the presence of tra
      genes on a helper plasmid, pBASGreen was directly mobilizable from E. coli into
      animal cells by trans-kingdom conjugation.

PMID- 9586048
TI  - Genome structure of pTi-SAKURA (I): strategy for DNA sequencing of a Japanese
      cherry-Ti plasmid.
AB  - We isolated a plasmid from a bacterium Agrobacterium tumefaciens, which had been
      found in a crown gall tumor on a Japanese cherry tree SAKURA and designated it
      pTi-SAKURA. For complete DNA sequencing, we constructed a DNA library in lambda
      phage vector and developed a sequencing method by primer walking with long PCR
      and a PCR subcloning technique for long insert DNA.

PMID- 9586049
TI  - Genome structure of pTi-SAKURA (II): genetic map constructed by complete DNA
      sequencing.
AB  - Ti plasmid (pTi-SAKURA) DNA isolated from an agrobacterium pathogenic against
      Japanese cherry trees were completely sequenced by primer walking with PCR
      subcloning. Typical genes including transfer DNA (T-DNA), nopaline utilizing
      genes, trb genes, traI, rep genes, tra genes, acc and vir genes were assigned in
      this order to pTi-SAKURA. Between the rep genes and tra genes, we found a large
      region which essentially lacks homology to any sequences in DNA databases. By
      amino acid sequence search, we could pick up several ORFs which are homologous
      with genes putatively capable to enhance interaction between agrobacteria and
      plants.

PMID- 9586050
TI  - High-salt effects on the structure and damage of chromosomal DNA in Halobacterium
      salinarium, an extremely halophilic bacterium.
AB  - High concentration salt effects on the structure and radiation-induced damages of
      DNA were studied to elucidate the biochemical mechanism of the resistance of
      halophilic H. salinarium against DNA damaging agents. High concentration of KCl
      did not induce significant conformational changes in H. salinarium chromosomal
      DNA, but exhibited an extensive protective effect on the radiation-induced single
      strand breaks of plasmid DNA.

PMID- 9586051
TI  - Mechanisms of the genotoxic effects associated with 5-formyluracil: effect of
      exogenous 5'-formyl-2'-deoxyuridine.
AB  - E. coli HB101 harboring plasmid pUC19 was grown in the presence of 5-formyl-2'
      deoxyuridine (fdU) to evaluate the genotoxic and cytotoxic potentials associated
      with this DNA lesion. Cell growth was inhibited by fdU in a concentration
      dependent manner, but increased mutation was not observed in the lacZ(alpha) gene
      of pUC19. The lack of the mutagenic effect was attributed to poor utilization of
      fdU as a substrate by thymidine kinase, which converts exogenous thymidine
      analogs to the corresponding 5'-monophosphates in the salvage pathway.

PMID- 9586052
TI  - Random amplified polymorphic DNA observed in Eucalyptus by PCR study with random
      primers.
AB  - A total DNA extracted from Eucalyptus globlus, E. citriodora, or a subspecies of
      E. gunnii (Maruha Yu-kari) being used as an template, Polymerase Chain Reaction
      (PCR) was performed with 40 kinds of commercially available random primers
      (Operon, OPA-01-20 and OPB-01-20). After electrophoresis of PCR-products on
      agarose gel, we analyzed the band pattern formed by DNA-fragments with 0.5-3.0
      kbp as molecular weight. As a remuneration for the examination in which forty 10
      mer arbitrary oligonucleotides were tried to be used as primers in PCR for each
      species, we found that 9 primers (for E. globlus) leads polymorphism, 6 primers
      for E. citriodora, and 6 primers for Maruha Yu-kari.

PMID- 9586053
TI  - Novel primers designed for microsatellite loci in Eucalyptus and identification
      by PCR fingerprints.
AB  - We found a novel PCR-primer which can be used for the identification on "elite
      tree-selection". This primer was designed for selective hybridization at the both
      ends of microsatellite loci, which is well known as one of the most
      highpervariable region of DNA. After PCR-fingerprinting on five Eucalyptus
      species (E. globulus, E.citriodora, E.grandis, E. maidenii, E.bicostata), with
      our primer, DNA-polymorphism was observed all over the cases.

PMID- 9586054
TI  - Identification of Eucalyptus citriodora clones micropropagated in tissue culture.
AB  - The extent of genetic identity observed in the young individuals which were
      micropropagated from a single Eucalyptus individual was analyzed by using DNA
      fingerprinting. Among 40,000 tissue-cultured-seedings of E.citriodora, 200 plants
      were randomly chosen so that each total DNA might be extracted from their leaves.
      Using these DNAs as template, PCR was performed with some primers we found in
      advance that leads polymorphism for DNA of E. citriodora. In this study, all over
      the 200 cases, the band pattern formed cDNA fragment on a gel after
      electrophoresis was the identical one mutually.

PMID- 9586055
TI  - Biological behaviour of 6-chloro-2',3'-dideoxyguanosine and 6-chloro-2',3'
      dideoxyinosine in the brains of mice.
AB  - By using tissue and blood from mice and mice themselves, biological behavior of 6
      chloro-2',3'-dideoxyguanosine (6-Cl-ddG) and 6-chloro-2',3'-dideoxyinosine (6-Cl
      ddI) was examined in vitro and in vivo. Both compounds resemble each other in
      chemical structure. They are converted to ddG and ddI, respectively, by adenosine
      deaminase in the cells, and express their anti-HIV activity in vitro. According
      to our recent data about their biological behaviour in vivo; however, it was
      revealed that they are fairly different especially as the agent working in the
      brain. After injection of each drug into the body of mice, ddG, or metabolite of
      6-Cl-ddG, was observed in the brain, while ddI was not found there.

PMID- 9586057
TI  - Synthesis of guanosine 5'-triphosphate analogues and their effect on microtubule
      assembly.
AB  - More than 20 base-modified analogues of guanosine 5'-triphosphate including 2'
      deoxyguanosine derivatives were synthesized and examined their effect on tubulin
      polymerization into microtubules (Mts). Among those, 2,6-diamino-8
      oxopurineriboside 5'-triphosphate (1d), 2,6-diamino-2'-deoxypurineriboside 5'-tri
      phosphate (1b) and 8-bromoguanosine 5'-tri phosphate (1g) were shown to have
      remarkable effect to promote microtubule assembly.

PMID- 9586056
TI  - Dissection of the DNA binding domain of yeast Zn-finger protein Rme1p, a
      repressor of meiotic activator IME1.
AB  - A series of deletion mutants of the yeast Zn-finger protein Rme1p (Repressor of
      Meiosis) fused with maltose binding protein (MBP) were constructed, purified, and
      characterized to examine the DNA binding domain. It was shown by gel retardation
      assay that the DNA binding domain of Rme1p was attributed to C-terminal amino
      acid residues 171 to 300. All three Zn-fingers are involved in the DNA binding
      domain, but they are not sufficient for DNA binding ability. Notably, the C
      terminal region (residues 285-300) is essential for DNA binding. Provided that
      the region folds into alpha-helix, the basic amino acid residues may form a ridge
      on one side of the helix, whereas the hydrophobic residues may form it on the
      other side. Thus, the DNA binding domain of Rme1p would be dissected two regions.
      The roles of C-terminal region in DNA recognition will be discussed.

PMID- 9586058
TI  - Translational pauses during the synthesis of proteins and mRNA structure.
AB  - Translational pauses are observed during a spider fibroin synthesis (1,2). The
      spider major ampullate (dragline) silk of the spider Nephila clavipes is composed
      of multiple proteins. The amino acid sequences of the partial cDNA clones for the
      two major dragline silk fibroin components (Spidroin 1 and 2) exhibit repetitive
      motifs (3,4). Our detailed inspection of the nucleotide sequences of the
      repetitive motifs revealed highly selective site-specific codon usage patterns
      within a motif, suggesting that the secondary structure of the spider fibroin
      mRNA is optimized by the nucleotide sequence of the fibroin gene. The results,
      combined with our preceding results on silk fibroin from Bombyx mori (5) suggest
      that translational pauses of spider silk are interpreted in terms of the mRNA
      secondary structure.

PMID- 9586059
TI  - Chiral influences of feedback inhibition with dCTP on murine deoxycytidine
      kinase.
AB  - The inhibitory effects of 4 kinds of 2'-deoxy-L-nucleoside 5'-triphosphates,
      which are enantiomers of natural dNTPs, on murine deoxycytidine kinase (dCK) were
      investigated. When ATP was used as the phosphate donor, L-dCTP showed significant
      inhibitory action noncompetitively and competitively with 2'-deoxycytidine (dCyd)
      and ATP, respectively. Thus L-dCTP, like dCTP, could serve as a feedback
      inhibitor for dCK. Recently, it has been demonstrated that human dCK can utilize
      L-dCyd as a substrate (Verri, A. et al. (1997) Mol. Pharmacol., 51, 132). The
      present results suggest that dCK is also unable to discriminate the chirality of
      nucleotides at the phosphate donor binding site of the enzyme.

PMID- 9586060
TI  - A mechanism for unsplicing and exon skipping in human alpha- and beta-globin
      mutant pre-mRNA splicing.
AB  - In both of normal human alpha- and beta-globin pre-mRNAs, two introns are spliced
      correctly, giving mRNA products of (exon 1)-(exon 2)-(exon 3). If 5'-splice site
      of the second intron is mutated, mRNA of the beta-globin is composed of (exon 1)
      (exon 3), skipping the whole exon 2 sequence. However, if 5'-splice site of the
      second intron is mutated in the alpha-globin, mRNA is (exon 1)-(exon 2)-(intron
      2)-(exon 3), unsplicing intron 2. In both of the alpha- and beta-globin pre
      mRNAs, strengths of 3'-splice signals of the first and second introns were
      calculated by the quantification method reported previously, which explains a
      reason for exon skipping and unsplicing in terms of relative strengths of those
      signals.

PMID- 9586061
TI  - Escherichia coli tmRNA (10Sa RNA) in trans-translation.
AB  - Here we show that Escherichia coli tmRNA (10Sa RNA) has a dual function both as
      an mRNA and as a tRNA in vitro. The function as a tRNA is prerequisite for the
      function as an mRNA. These observations strongly support the trans-translation
      hypothesis.

PMID- 9586062
TI  - Purification of a Mycoplasma capricolum MCS4 RNA binding protein and cloning its
      gene.
AB  - MCS4 RNA (125 nt in length) is one of the small stable RNAs found in Mycoplasma
      capricolum cells. Gel shift assay was performed with the 5' end-32P-labeled MCS4
      RNA and the S100 fraction from M. capricolum to identify the RNA binding
      proteins. Several bands were detected above free MCS4 RNA, indicating that the
      RNA formed complexes with proteins and/or RNAs. One of the proteins which
      specifically binds to MCS4 RNA was purified. The amino acid sequence of the N
      terminus revealed 60 to 80% identity to those of glyceraldehyde-3-phosphate
      dehydrogenases (GAPDH) from various sources.

PMID- 9586063
TI  - Essentially minimal sequence for substrate recognition by tRNA (guanosine-2')
      methyltransferase from Thermus thermophilus HB27.
AB  - Transfer RNA (guanosine-2'-)-methyltransferase (Gm-methylase, EC.2.1.1.32) from
      extreme thermophile, Thermus thermophilus HB27 is one of the tRNA-ribose
      modification enzymes; this enzyme specifically catalyze the transfer of a methyl
      group from S-adenosyl-L-methionine to 2'-OH of the ribose of the guanosine at
      position 18 in tRNA. A broad substrate specificity of Gm-methylase was observed
      using natural tRNAs as methyl group acceptors, which suggests that some local
      stractures common in tRNAs are recognized by the enzyme. By using yeast tRNA(Phe)
      variants obtained by transcription of their genes with T7 RNA polymerase, it was
      revealed that the residues G18 and G19, as well as the D-stem structure were
      primarily required for the methylation reaction and that the essentially minimal
      sequence for the substrate was Pyrimidine17-G18-G19. The other conserved
      sequences and the tertiary base-pairs were not essential, but G15, G46, U55 and
      C56 strongly affected the methylation efficiency.

PMID- 9586064
TI  - Expression of Xenopus laevis translation initiation factor 4E (eIF-4E) by
      baculovirus-insect cell system.
AB  - A gene encoding Xenopus laevis eIF-4E was cloned into a transfer vector, and its
      gene expression was attempted in cells of E. coli, yeast and insect. Effective
      expression of the active eIF-4E was achieved in the soluble fraction of the
      insect cell Sf9, which was infected with the recombinant baculovirus.
      Overexpression of the eIF-4E protein caused remarkable change in the shape of the
      cells.

PMID- 9586065
TI  - Effect of a low-calcium environment on EGF inducible AP-1 binding activity in
      osteoblastic MC3T3-E1 cells.
AB  - In the mouse osteoblastic cell line MC3T3-E1, the signaling response of DNA
      binding protein induced by the treatment of epidermal growth factor (EGF) was
      examined using electrophoretic mobility shift assay. EGF increased the binding
      activity in nuclear extracts of MC3T3-E1 cells to TPA-responsive element (TRE).
      Competition experiments revealed that the binding activity to AP-1 site in the
      nuclear extracts of EGF treated MC3T3-E1 cells was entirely inhibited by
      unlabeled AP-1 consensus oligonucleotide. The DNA-binding activity of AP-1 by EGF
      in nuclear extracts of MC3T3-E1 cells cultured under a low calcium environment
      was more increased.

PMID- 9586066
TI  - Mitochondrial methionyl-tRNA transformylase from bovine liver.
AB  - Substrate specificities of mammalian mitochondrial methionyl-tRNA transformylase
      (MTFmt) toward tRNA substrates were characterized in vitro. The MTFmt is able to
      formylate E. coli initiator methionyl-tRNA (Met-tRNA(fMet)) as efficiently as
      mammalian mitochondrial methionyl-tRNA. Furthermore, E. coli elongator methionyl
      tRNA (Met-tRNA(mMet)) also serves as a substrate for mt MTF, whereas E. coli MTF
      rigorously excludes E. coli Met-tRNA(mMet) from formylation reaction. Thus,
      mammal mt MTF is suggested to have recognition mechanism different from E. coli
      MTF. To pursue the relationship between protein structure and unexpected
      substrate specificity of mammalian MTFmt, the nucleotide sequence of MTFmt gene
      was determined and its amino acids sequence was compared to other MTFs of
      prokaryotic origin.

PMID- 9586067
TI  - 5-formylcytidine (f5C) found at the wobble position of the anticodon of squid
      mitochondrial tRNA(Met)CAU.
AB  - In squid (Loligo breekeri) mitochondria, AUA codons are translated as methionine
      instead of the universal isoleucine. Here, we present the nucleotide sequence of
      squid mitochondrial tRNA(Met)CAU. This tRNA(Met)CAU has 5-formylcytidine (f5C) at
      the wobble position of the anticodon, though it is partially modified. This
      result indicates the common feature with bovine and nematoda mitochondrial
      systems in that f5C at the wobble position of the anticodon is very likely
      involved in translation of AUA codons as methionine in squid mitochondria.

PMID- 9586068
TI  - Stabilities of internal rU-dG and rG-dT pairs in RNA/DNA hybrids.
AB  - We report stabilities of internal non-Watson-Crick rU-dG and rG-dT pairs in
      RNA/DNA hybrids. UV melting curves revealed that a hybrid containing internal rG
      dT pair had about 2 kcal mol-1 greater stability in free energy change at 37
      degrees C than hybrids with other mismatches, rA-dA and rU-dT, at the same
      position. We discuss why internal rG-dT as well as rU-dG is stable nearly Watson
      Crick base pairs rather than the other mismatches.

PMID- 9586069
TI  - Evolution of a phosphorothioate RNA library during in vitro selection.
AB  - We carried out an in vitro selection of aptamers from an RNA library with
      phosphorothioate linkages instead of normal phosphodiesters. This "thio-RNA"
      library had smaller dissociation rate constant (kd) to a target protein than a
      natural RNA library. On the basis of the results, an improved selection procedure
      to obtain ideal nucleic acid drugs will be discussed.

PMID- 9586070
TI  - Gene regulation by decoy approach (I): synthesis and properties of photo
      crosslinked oligonucleotides.
AB  - To explore gene regulation by double stranded oligonucleotides as decoy molecules
      for transcriptional factors, oligodeoxyribonucleotides (ODN) and the
      complementary oligo(deoxyribonucleoside phosphorothioate)s (OPT) were photo
      crosslinked by use of psoralen. UV melting curves showed that the thermal
      stability of crosslinked duplexes increased compared with that of non-crosslinked
      ones. CD spectra showed that the photo-crosslinked duplexes formed B-DNA
      structure. In addition, cross-linked duplexes were resistant against digestion by
      snake venom phosphodiesterase. These results suggest that the photo-crosslinked
      duplexes have desirable characteristics as decoy molecules.

PMID- 9586071
TI  - Study of RNA structure by pyrene-labeled oligonucleotides.
AB  - Fluorescent-labeled oligonucleotides containing 2'-(1-pyrenylmethyl) uridine
      (Upy) that have G or C adjacent to 3'-site of Upy, I and II, respectively, showed
      a remarkable increase in the emission intensity when they hybridized with the
      complementary oligoribonucleotides (ORN). However such change was not observed
      when they hybridized with the complementary oligodeoxyribonucleotides(ODN). Tm
      values derived from the UV melting curves for I-ORN and II-ORN duplexes were 5
      degrees C and 10 degrees C lower than the normal duplexes without Upy,
      respectively. The intensity of induced CD based on the pyrene groups for the I
      ORN and II-ORN duplexes were a half of that for the corresponding I-ODN and II
      ODN duplexes. These results suggest that pyrene groups were released from the
      stacking interaction upon duplex formation and that the remarkable change of
      emission intensity was then occurred. Based on these properties, it is suggested
      that Upy-probes that have G or C adjacent to 3'-site of Upy can be useful to
      search the single strand region of RNA.

PMID- 9586072
TI  - Structural analysis of nucleic acids by using fluorescence resonance energy
      transfer (FRET).
AB  - We examined changes in the extent of fluorescence resonance energy transfer
      (FRET) between two different fluorochromes attached to a single oligonucleotide
      in the presence or absence of target nucleic acids with a specific sequence and a
      higher-ordered structure. In our system, FRET was maximal when probes were free
      in solution and a decrease in FRET was evidence of successful hybridization.
      Incubation of the probe with a single-stranded complementary oligonucleotide
      reduced the FRET. While, a small change in FRET was also observed when the probe
      was incubated with an oligonucleotide in which the target site had been embedded
      in a stable hairpin structure. These results indicate that this
      spectrofluorometric method and FRET probes can be used to estimate the efficacy
      of hybridization between a probe and its target site within highly ordered
      structures. It should help us to estimate the suitability of designed functional
      molecules, such as antisense DNA and RNA and ribozymes, that target to specific
      sites.

PMID- 9586073
TI  - Sequence-selective RNA scission by oligoamine--DNA conjugates (1).
AB  - Ethylenediamine and diethylenetriamine, which are active for RNA hydrolysis, are
      attached to the 5'-ends of synthetic oligonucleotides by urethane linkages. The
      resultant artificial ribonucleases selectively hydrolyze the substrate RNA at the
      target phosphodiester linkage. Acid/base cooperation in the oligoamines for the
      catalysis is confirmed in terms of kinetic evidences.

PMID- 9586074
TI  - Homogeneous catalyst for DNA hydrolysis (4). Efficient DNA hydrolysis by
      lanthanide--saccharide complexes.
AB  - Homogeneous and neutral solutions are prepared by mixing Ce(NH4)2(NO3)6 with
      either isomaltose, melibiose, gentiobiose, palatinose, mannitol, sorbitol,
      galactitol, or glucamine in pH 7 hepes buffer ([Ce(IV)]0/[monomeric residue of
      saccharide]0 = 1). In contrast, amylose, cyclodextrins, maltose, glucose, and
      fructose provide only heterogeneous mixtures. The homogeneous solution of 1:1
      Ce(IV)/glucamine system is active for DNA hydrolysis: the pseudo-first-order rate
      constant for the hydrolysis of thymidylyl(3'-->5')thymidine at pH 7.0 and 50
      degrees C is 0.010 h-1, when [Ce(IV)]0 = [glucamine]0 = 10 mmol dm-3. The DNA
      hydrolyzing activity decreases in the following order: glucamine > isomaltose,
      melibiose, gentiobiose >> palatinose, mannitol, sorbitol, galactitol.

PMID- 9586075
TI  - Comparison of activities between hammerhead ribozymes and DNA enzymes targeted to
      L6 BCR-ABL chimeric (b2a2) mRNA.
AB  - For the treatment of chronic myelogenous leukemia (CML), attempts have been made
      to design hammerhead ribozymes that can specifically cleave BCR-ABL fusion mRNA.
      In the case of L6 BCR-ABL fusion mRNA (b2a2 type), which has no effective
      cleavage sites for conventional hammerhead ribozymes near the BCR-ABL junction,
      it has proved very difficult to cleave the chimeric mRNA specifically. Several
      hammerhead ribozymes with relatively long junction-recognition sequences have
      poor substrate-specificity. Therefore, we explored the possibility of using DNA
      enzymes, that was newly selected by Santoro & Joyce and that can cleave RNA
      molecules with high activity, to cleave of L6 BCR-ABL fusion (b2a2) mRNA. By
      contrast to the results with the conventional ribozymes, the newly designed DNA
      enzymes, having higher flexibility for selection of cleavage sites, were able to
      cleave this chimeric RNA molecule specifically at sites close to the junction,
      without any cleavage of the normal ABL or BCR mRNA.

PMID- 9586076
TI  - Synthesis and anti-HIV activity of phosphorothioate antisense DNA containing C-5
      polyamine substituted 2'-deoxyuridine and/or acridine residues.
AB  - Novel phosphorotioate DNAs (S-ODNs) bearing polyamine moiety at the C-5 position
      of 2'-deoxyuridine in place of certain thymidine residues and/or an acridine
      moiety at the 5'-terminus were prepared. The sequence of the S-ODNs is
      complementary to the rev region of HIV-1 mRNA. The duplexes consisted of the
      modified S-ODNs and the complementary DNA exhibited the enhanced stability
      compared to that consisted of the corresponding unmodified S-ODN and the
      complement. The improved antisense activity against HIV-1 was also observed for
      all modified S-ODNs.

PMID- 9586077
TI  - Study on site specific cleavage of RNA.
AB  - The precursor of an RNA molecule from bacteriophage T4 infected Escherichia coli
      cell (p2Sp1 RNA) has the ability to cleave itself. It has been found that the
      site specific RNA cleavage reaction occurred at the pyridine-adenosine sequence
      in the presence of a monovalent cation and a non-ionic detergent. In order to
      investigate the mechanism of this cleavage reaction, we designed a RNA
      oligonucleotide (UUUAUU) and this RNA was cleavage activity at the U-A sequence.

PMID- 9586079
TI  - Inhibition of HIV-1 replication by foldback triple-helix forming
      oligonucleotides.
AB  - Replication of retroviral RNA into double-stranded DNA is catalyzed by reverse
      transcriptase (RT). The polypurine tract (PPT) serves as a primer for plus-strand
      DNA synthesis and is highly conserved among HIV-1. The PPT region is a possible
      target for triple-helix formation. Here, we show the effects of triple-helix
      formation by analyses of melting temperature and gel shift using a foldback
      triplex-forming-oligonucleotides (FTFOs). We found that the FTFOs containing
      phosphorothioate groups at the 3'- and 5'-ends, or inside the hairpin loop,
      exhibited greater exonuclease resistance than the unmodified FTFOs. Several
      triplex oligonucleotides have thermal stability. The abilities of the FTFOs (DsDG
      37) containing the guanosine in place of the cytidine in the third Hoogsteen base
      pairing strand to inhibit HIV-1 replications were examined. The FTFOs (DsDG-37)
      inhibit the replication of HIV-1 more efficiently than the FTFOs (DsD-37)
      indicating sequence-specific inhibition of HIV-1 replication.

PMID- 9586078
TI  - Synthesis and anti-influenza virus-A activity of circular dumbbell RNA DNA
      chimeric oligonucleotides.
AB  - We have designed a new type of antisense oligonucleotide, containing two hairpin
      loop structures with RNA/DNA base pairs (sense (RNA) and antisense (DNA)) in the
      double helical stem (nicked and circular dumbbell DNA/RNA chimeric
      oligonucleotides). The reaction of the nicked and circular dumbbell DNA/RNA
      chimeric oligonucleotides with RNase H gave the corresponding anti-DNA together
      with the sense RNA cleavage products. These oligonucleotides were more resistant
      to exonuclease attack. We also describe the anti-Fluv activities of circular
      dumbbell DNA/RNA chimeric oligonucleotides.

PMID- 9586080
TI  - Design and in vitro activity of ribozymes against mRNA of a rat membrane
      inhibitor of complement.
AB  - Mammalian cells are usually protected from the complement-mediated injury by a
      number of complement regulatory proteins. A rat protein designated as 512 antigen
      is thought to be such a complement regulatory protein. A cDNA of 512 antigen has
      been cloned and analyzed. To investigate the function of 512 antigen, we plan to
      construct a ribozyme system against 512 antigen expression. We have designed two
      hammerhead ribozymes targeted to the 512 antigen mRNA and tested the ribozyme
      activities in vitro. Both hammerhead ribozymes efficiently cleaved the 512
      antigen mRNA in vitro. We have also designed a hairpin ribozyme against this
      mRNA. The activity of the hairpin ribozyme will also be discussed.

PMID- 9586081
TI  - Poly(L-lysine)-graft-dextran copolymer is a novel stabilizer of triplex DNA (I):
      stabilization of poly(dA).2poly(dT) triplex.
AB  - Comb-type polylysine copolymer having grafted hydrophilic side chains was newly
      designed as a novel stabilizer of triplex DNAs. The comb-type copolymer elevated
      melting temperature of poly(dA).2poly(dT) triplex by 50 degrees C without
      affecting reversibility, melting and reassociation, of the triplex in buffer with
      physiological salt concentrations. The stabilizing effect of the copolymer was
      greater than spermine. Our results indicate that the molecular designing of
      polycation with comb-type structure is a successful strategy for creating an
      effective triplex stabilizer.

PMID- 9586082
TI  - Three-dimensional model of Tetrahymena group I intron.
AB  - The modelling of the folding structure of Tetrahymena group I intron have been
      carried out, using the molecular mechanics programs; Insight II and Discover.
      This model has long-range interactions between the P2.1 loop region and the 3'
      exon, and between the P9.1a and P5c loop regions.

PMID- 9586083
TI  - Hypnotic activities of N3-benzyl and xylyl substituted arabinofuranosyluracil.
AB  - N3-Substituted derivatives of arabinofuranosyluracil (1), methyl (2), ethyl (3),
      propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyls (8, 9, 10) and
      alpha-phenethyl (11) derivatives, were synthesized and their CNS depressant
      effects were evaluated by intracerebroventricular (i.c.v.) injection in mice by
      using hypnotic activity and pentobarbital-induced sleep prolongation as indices.
      At a dose of 2.0 mumol/mouse, the values of mean sleeping time induced by 7, 8,
      9, and 10 were 144, 154, 117, and 33 min, respectively. Although the alkyl (2-6)
      derivatives did not cause any hypnotic activity, some derivatives tested (5, 7
      10) significantly prolonged the pentobarbital-induced sleeping time.

PMID- 9586085
TI  - DNA labeling reagent containing carbodiimide.
AB  - We have synthesized a number of fluorescent compounds having a carbodiimide
      function and tested if it can be used to label DNA. They all reacted well with
      DNA in a very short time. Some of them showed different fluorescent
      characteristics when they bound to DNA such as band shift or change in
      fluorescent intensity.

PMID- 9586084
TI  - Luminescence properties of lanthanide ion-phenanthroline DNA triple helix
      systems.
AB  - A method to identify dyad symmetrical sequence on duplex DNA in a homogeneous
      system has been investigated. In this method, luminescence from the complex of
      Tb(III)-phenanthroline-DNA triple helix was utilized.

PMID- 9586086
TI  - Affinity capillary electrophoresis using DNA conjugates.
AB  - An oligonucleotide ((dT)12)-immobilized capillary was prepared for the affinity
      capillary electrophoresis of DNA. Oligonucleotides ((dA)6 and (dT)6) which had
      the same chain length but had different base composition were separated in high
      resolution in the presence of Mg2+ ion. Whereas (dA)6 eluted slightly earlier
      than (dT)6 in a conventional polyacrylamide-coated capillary, the order of their
      mobilities was reversed in the (dT)12-modified system, suggesting the
      complementary hydrogen bondings between (dA)6 and the immobilized (dT)12.

PMID- 9586087
TI  - Specific RNA aptamers to NS3 protease domain of hepatitis C virus.
AB  - In order to isolate RNA aptamers that bind specifically to NS3 protease domain
      (delta NS3) of hepatitis C virus, we carried out in vitro selection procedure
      using RNA pool that had 30 N random core region. After repeating nine cycles of
      selections and amplifications, a pool of RNAs that bind specifically to the delta
      NS3 were selected. A comparative analysis of 45 clones that were isolated from
      9th cycle revealed three main classes that contain the conserved loop sequences
      GANUGGGAC. Moreover, the predominant class of aptamer (class I and III) appear to
      inhibit the protease activity efficiently.

PMID- 9586088
TI  - Detection of 2'-deoxyoxanosine by capillary electrophoresis.
AB  - We have investigated capillary electrophoresis separation of oxanine (Oxa), a
      base moiety of 2'-deoxyoxanosine (Figure 1), from various bases. Oxa was not well
      separated from the others by micelle electrokinetic chromatography which is a
      general method for separating of the bases. On the other hand, capillary zone
      electrophoresis showed much improved separation when used pH 12 where the six
      membered ring of Oxa is opened.

PMID- 9586090
TI  - Selection of functional DNAs which bind to a transition state analog.
AB  - Selection of single strand DNA molecules which bind to a transition state
      analogue of carboxyl ester hydrolysis was demonstrated. After the 9th round of
      selection, ssDNAs with the affinity to TSA were enriched.

PMID- 9586089
TI  - Intermediate in reaction of 2'-deoxycytidine with nitrous acid.
AB  - Using reversed phase (RP) HPLC analysis, we reinvestigated the reaction of dCyd
      with nitrous acid. When 10 mM 2'-deoxycytidine (dCyd) was incubated with 100 mM
      NaNO2 in 1.0 M acetate buffer (pH 3.7) at 37 degrees C, an unknown product
      (referred to compound 1) was detected. The time course of the yield of compound 1
      showed profile characteristic of an intermediate. Under the physiological
      conditions, compound 1 was converted exclusively to dUrd with a life time of ca.
      300 h. Elucidation of genotoxic effects of compound 1 may be an important subject
      of the future study.

PMID- 9586091
TI  - Mechanistic analogy between metal ion-catalyzed self-splicing of protein and RNA.
AB  - Recent studies have shown that RNA hydrolysis is remarkably promoted by metal
      ions and suitably designed metal complexes. We have found that autocleavage of
      dipeptides X-Ser and a tripeptide Gly-Ser-Ala is catalyzed by Zn(II) at 70
      degrees C and pH 7.0. A mechanistic analogy between metal ion-catalyzed
      hydrolysis of peptides and RNA is suggested.

PMID- 9586092
TI  - Novel detection system of flow injection analysis (1). The existence of
      significant relation between secondary structure of DNA and sensitivity in signal
      detection.
AB  - Polymerase Chain Reaction (PCR) products was detected quantitatively using a flow
      injection type sensor, based on Surface Plasmon Resonance (SPR). We used
      asymmetric PCR to amplify the two kinds of products; their DNA lengths are
      different. This novel design permitted us not only to detect PCR products with
      high-sensitivity, but also to develop a rapid DNA detection system for the sense
      of the genetic pathogen.

PMID- 9586093
TI  - RNA aptamers to a protease, subtilisin.
AB  - RNA ligands (RNA aptamers) to a protease subtilisin were selected from pools of
      random RNA using SELEX (Systematic evolution of ligands by exponential
      enrichment). We selected RNA aptamers using a subtilisin-immobilized Sepharose
      column. After several rounds of selection, we obtained RNA aptamers that
      specifically inhibit the subtilisin activity. Characterization of the RNA
      aptamers will be reported.

PMID- 9586094
TI  - Interaction between tris(bpyl)osmium(II/III) complex and immobilized DNA on a
      carbon electrode.
AB  - Interaction between (bipyridyl) osmium (II/III) complex and immobilized DNA on a
      carbon paste electrode was studied using cyclic voltammetry and chronocoulometry.
      The complex specifically interacted with immobilized double strand DNA (20 mer).

PMID- 9586095
TI  - Recognition of DNA sequence utilizing osmium complex by amperometric technique.
AB  - Recognition of DNA sequence utilizing tris-(bipyridyl)osmium(II/III) complex was
      studied, because the osmium complex interacted with double strand DNA
      specifically. In this result, double strand DNA (12-20 mer) could be recognized
      selectivity.

PMID- 9586096
TI  - Structural analogues of TaqMan probes for real-time quantitative PCR.
AB  - We have prepared and evaluated a series of structural analogues of TaqMan PCR
      probes in an effort to identify second-generation probes with improved physical
      properties and performance. Modifications have included non-nucleosidic dye
      linkers, 2'-O-Me RNA substitutions, and pyrimidine C5-propyne substitutions.

PMID- 9586098
TI  - Modified nucleic acids for in vitro selection.
AB  - Some types of modified nucleic acid were tested for in vitro evolution or
      systematic evolution of ligands by exponential enrichment (SELEX). T7 RNA
      polymerase accepted cytidine triphosphate carrying biotinyl group at the N4
      position of cytosine, adenosine triphosphate carrying aminohexyl group at the N6
      position of adenine, and 2'-amino-2'-deoxyuridine triphosphate as substrates for
      transcription of DNA containing random sequence, but not uridine triphosphate
      carrying a nitroveratryloxy group at the 2'-position nor adenosine triphosphate
      carrying aminohexyl group at the 8-position of adenine. The transcribed products
      served as templates for cDNA by reverse transcription. These findings indicate
      that some modified nucleotides can be applied to the present in vitro selection.

PMID- 9586097
TI  - Thrombin-binding properties of thrombin aptamer derivatives.
AB  - We synthesized a single-stranded DNA with triple G-quartet structure and found
      that its thrombin-binding activity at 37 degrees C is as much as that of thrombin
      aptamer with double G-quartet structure which is a product of in vitro selection
      and amplification. This result suggests that the sequence motifs obtained by in
      vitro selection and amplification method might not be the only answer.

PMID- 9586099
TI  - Inclusion of nucleic acid contribution into assessment of protein 3d-1D
      compatibility and prediction of binding sites for nucleic acids.
AB  - The novel three dimensional structure(3D)-amino acid sequence(1D) compatibility
      program, 3d-1D method has developed and expanded into protein-nucleic acid
      system. The environment characteristics are determined using the coordinates of
      backbone atoms and C beta atom. This simplified estimation allows the expanded
      application to monitor the change of environment class depending on different
      sequence alignment. This method has improved the detective performance of the
      different protein into the similar folds. If protein has a wide contact with
      nucleic acid molecule, the compatibility profile goes down in the contact region
      without ligand molecule. This phenomenon becomes useful to monitor the binding
      sites of the bulky ligand such as nucleic acid and to model the protein-nucleic
      acid complex.

PMID- 9586100
TI  - Non-enzymatic hydrolyses of aryl esters of thymidine 3'-monophosphate as probes
      for the rate-determining step in DNA hydrolysis.
AB  - In order to shed light on the rate-limiting step in DNA hydrolysis, non-enzymatic
      hydrolyses of aryl esters of thymidine 3'-monophosphate have been kinetically
      examined. In alkaline solutions, these dinucleotide analogues were hydrolyzed far
      faster than was thymidylyl(3'-5')thymidine (TpT), indicating that the departure
      of the leaving group from the phosphorus atom is rate-limiting. The CeIV- and
      CeIV/PrIII combination-mediated hydrolyses of these analogues were also faster
      than the corresponding hydrolysis of the dinucleotide.

PMID- 9586101
TI  - DNA sequence dependent binding modes of bis(vinylpyridinium)benzene derivatives.
AB  - The DNA binding selectivity of new dicationic ligands based on the
      bis(vinylpyridinium)benzene unit has been investigated by means of UV-Vis
      absorption spectroscopy. From the experimental results it is concluded that these
      extended pi-electron bridged viologens have relatively high affinity to AT base
      pair sequences whereas the binding to GC pairs is about 10 times lower, and
      binding affinity depends on minor variation in the ligand structure. Linear type
      ligand exhibits two binding mode interaction, intercalation at high dye
      concentration which undergoes switching to groove binding at low ligand
      concentration.

PMID- 9586102
TI  - Effect of chemical modification of oligohomopyrimidine on triplex formation:
      thermodynamic and kinetic studies.
AB  - To investigate the effect of chemical modification of the third strand on the
      stability of triplex DNA, we have examined the thermodynamic properties of the
      triplex formation between a 23-mer double-stranded homopurine-homopyrimidine and
      each of five kinds of 15-mer chemically modified single-stranded homopyrimidines
      by isothermal titration calorimetry, and the kinetic properties by interaction
      analysis system. The modifications of the third strand included two base
      modifications, two sugar moiety modifications, and one phosphate backbone
      modification. The thermodynamic and kinetic parameters for the triplex formation
      were similar in magnitude among the two base-modified and two sugar-modified
      single strands. By contrast, the binding constant for the triplex formation with
      the single strand with phosphorothioate backbone was more than ten times as small
      as that for the other triplex formation. On the basis of the kinetic analyses,
      the single strand with phosphorothioate backbone was more difficult to associate
      with and easier to dissociate from the target double strand than the other single
      strands, which resulted in the much smaller binding constant.

PMID- 9586103
TI  - Conformational distortion of sugar moieties in the RecA-bound DNA structure
      determined by a simulated annealing method.
AB  - We recently reported an NMR study indicating that the DNA structure bound to RecA
      protein contains a novel deoxyribose-base stacking interaction. Although the
      final structure calculated by the simulated annealing was well defined, the type
      of sugar puckers was neither pure C2'-endo nor C3'-endo, but something in
      between. This implies that the sugar moieties in the RecA-bound state actually
      take an intermediate puckering, but we can not exclude the possibility that RecA
      bound DNA takes multiple conformations between the S-type and N-type of sugar
      puckers. In either case, the DNA structure within RecA filaments shows a unique
      property that is distinct from canonical DNA structures.

PMID- 9586104
TI  - Structure model and physicochemical properties of the C-U mismatch pair in the
      double stranded RNA in solution.
AB  - Structure of the C-U mismatch pair was reported only in crystal but none in
      solution. Here we have studied the structure and physicochemical properties of
      the C-U mismatch pair in a double stranded RNA in solution. RNA oligomers
      r(CGACUCAGG) and r(CCUGCGUCG) form a double stranded structure with the C-U pair.
      The arrangement of the C-U pair derived from the model building based on nOe
      gives a similar structural feature to that in crystal. The modeling reveals that
      the amino-proton of cytidine and the keto-oxygen of uridine are located within
      hydrogen bonding distance, and the imino proton of uridine is exposed to bulk
      water. From the melting experiment which monitors chemical shifts of non
      exchangeable protons, the melting of all the base-pairs including the C-U pair
      occurs simultaneously. This suggests the possibility where the C-U mismatch pair
      is stacked on the neighboring base-pairs in the double helix until the duplex is
      denatured to single strands.

PMID- 9586105
TI  - Preparation and characterization of antibacterial alginate film containing DNA as
      a carrier of silver ion.
AB  - Silver ion was effectively bound to alginate film by the aid of DNA. Amounts of
      Ag(I) bound to the films (18 mm x 18 mm) were 4.2 micrograms and 24.7 micrograms
      in the absence and presence of DNA, respectively. The Ag(I)-induced films showed
      antibacterial activity for both of Escherichiacoli (E. coli) and Staphylococcus
      aureus (S. aureus), and the activity of DNA-alginate film was obviously larger
      than alginate film. These results indicate that Ag(I) induced in the DNA-alginate
      film keeps the potent antibacterial activity, and so DNA is very useful as a
      carrier of silver ion in the alginate film.

PMID- 9586106
TI  - Morphological variation in folded duplex DNA chains.
AB  - I have monitored the packaging process of giant DNA chains with various
      condensing agents, such as polyamines, polyethylene glycol having pendant
      aminogroups and a lipospermine, under fluorescence microscopy. The detail
      morphological structure of the compacted DNA has been observed using electron
      microscopy. It has become clear that the difference in the folding process
      results in a large polymorphism of compacted DNA. I discuss the biological
      importance of controlling the compacted structure.

PMID- 9586107
TI  - Detection, purification and characterization of a protein that binds the (6-4)
      photoproduct-containing DNA in HeLa cells.
AB  - HeLa cell proteins that bind DNA containing the pyrimidine(6-4)pyrimidone
      photoproduct were detected by the electrophoretic mobility shift assay using
      synthetic oligonucleotide duplexes as probes. The major species was purified to
      near homogeneity, and the amino acid sequences of the proteolytic peptides
      revealed that it was the human damage-specific DNA-binding protein, which was
      reported previously. The substrate specificity of this protein was determined
      using damaged or modified DNA duplexes.

PMID- 9586108
TI  - Characterization of DNA fragments that show anomalously rapid migration in non
      denaturing polyacrylamide gels.
AB  - Several DNA fragments that show anomalously rapid migration in nondenaturing
      polyacrylamide gels have been cloned from digests of bovine genomic DNA.
      Electrophoretic behaviors of these fragments were analyzed in detail under
      various conditions. The results indicated that these fragments may adopt non-B
      DNA conformation.

PMID- 9586109
TI  - Preliminary studies for interaction of a cyclobutane thymine dimer region with
      its cognate antibody.
AB  - A monoclonal antibody (TDM-2) specific to a UV-induced cyclobutane pyrimidine
      dimer has previously been established. We investigated here the structural
      requirements of antigen recognition by the antibody using chemically synthesized
      antigen analogs. TDM-2 bound to the cis-syn, but not the trans-syn thymine dimer,
      and recognized not only the cyclobutane ring but also the 5'- or 3'-side
      phosphate groups flanking the cyclobutane dimer site. The antibody showed strong
      binding to photodimer-containing single stranded DNA but indicated little binding
      to double stranded DNA.

PMID- 9586110
TI  - In vitro selection of aptamers that bind to ribosome-inactivating toxins.
AB  - Ribosome-inactivating proteins, such as ricin, pepocin and gypsophilin, catalyze
      the hydrolysis of a single N-glycosidic bond at a specific position in rRNAs.
      Aptamers targeting pepocin were selected from a random sequence RNA pool that
      spanned 30 positions. After 8 rounds, the anti-pepocin aptamers were sequenced
      and a conserved hairpin motif was identified. Interestingly, the selected motif
      is quite different from the toxin-binding domains of rRNAs.

PMID- 9586111
TI  - Crystal structures of nucleic acid complexes of ribonuclease U2.
AB  - Crystal structures of adenine-specific Ustilago sphaerogena ribonuclease U2
      complexed with the substrate analogues, d(ApG), d(ApGpG), and d(ApGpC), with the
      intermediate analogue, 2',3'-O-isopropylidene-adenosine, and with the product, 3'
      AMP, have been determined. In each structure, the adenine base is recognized by
      the enzyme with four hydrogen-bonds. In the substrate analogue structures, the
      second base of guanine is sandwiched between His 101 and Tyr 107 side-chains, and
      forms two hydrogen-bonds with Tyr 107 O and Asp 108 O delta 1 atoms. The third
      base of the trinucleotides is in van der Waals interaction with the Tyr 78 side
      chain. The phosphate group between the second and third nucleosides forms two
      hydrogen-bonds with the side chains of Asp 37 and Tyr 78. Oxygen atoms of the
      scissile phosphate group are involved in interactions with catalytic residues of
      Tyr 39, His 41, Glu 62, Arg 85, and His 101. These interactions indicate that
      either His 41 or Glu 62 acts as a general base and His 101 acts as a general acid
      in the first step of RNA hydrolysis.

PMID- 9586112
TI  - Colicin E5 as a new type of cytotoxin, which cleaves a specific group of tRNAs.
AB  - The C-terminal active domain of colicin E5 has a novel ribonuclease activity
      which specifically cleaves queuine-containing tRNAs. Colicin E5 is a new type
      cytotoxin targeting a group of tRNAs.

PMID- 9586113
TI  - Yeast oligonucleotide transformation: its mechanism and application to analysis
      of mutations induced by defined DNA lesions.
AB  - We have studied mutagenic specificity of an abasic site by the yeast
      transformation procedure using an oligonucleotide containing a single furan-type
      abasic site. The recipient yeast used was deficient in the major AP endonuclease
      (apn1). Sequence analysis of the transformants suggested that dATP was
      incorporated most frequently opposite the abasic site, while dGTP seemed to be
      incorporated opposite the abasic site in the recipient proficient in apn1. To
      explore the mechanism of this oligonucleotide transformation, we have also
      analyzed the transformation with phosphorothioate oligonucleotides with
      mismatched 3'-end. The results are discussed.

PMID- 9586114
TI  - Mammalian tRNA(Lys)3 and pre-tRNA(Lys)3 variants as primers and inhibitors of
      viral cDNA synthesis by HIV reverse transcriptase in vitro.
AB  - We constructed a set of mammalian tRNA(Lys)3-pseudogenes, whose pre-tRNAs are
      processing-deficient in HeLa extract. The 3'-flanking region was designed
      partially or completely complementary to the PBS-flanking nucleotides of the U5
      region of HIV-1 genomic RNA. We show that only the pre-tRNA with completely
      hybridized 3'-flanking region is efficiently extended by the HIV-1 reverse
      transcriptase, whereas the partially complementary pre-tRNA(Lys)3, the 3'
      terminal 10 nucleotides of which are not hybridized to the viral template, is
      unable to prime the cDNA-synthesis.

PMID- 9586115
TI  - A variant of Plasmodium ovale; analysis of its 18S ribosomal RNA gene sequence.
AB  - We report here a new variant of human malaria parasite found by comparison of
      diagnostic results obtained from a new DNA diagnostic method named microtiter
      plate-hybridization (MPH) and traditional microscopic method. Total five cases of
      malaria were diagnosed as microscopy-positive but MPH-negative; one case was
      found in epidemiological research in Vietnam and four cases were obtained from
      imported malaria in Japan. Although they were quite similar to typical P. ovale
      morphologically in microscopy, sequence analysis of PCR-amplified DNA fragment
      revealed that their 18S ribosomal RNA gene sequence was different from published
      sequence of P. ovale. Combination of MPH and microscopic examination provides us
      a new method for detection of a new type of malaria parasite which is difficult
      to distinguish morphologically.

PMID- 9586116
TI  - Recognition system of class II tRNA in Escherichia coli and yeast.
AB  - The recognition system of class II tRNA, tRNA(Ser) and tRNA(Leu), in a yeast
      Saccharomyces cerevisiae was studied using T7 RNA polymerase transcription
      system. Yeast SerRS recognizes the long variable arm as in E. coli. However, the
      anticodon loop of tRNA(Leu), which has no effect on leucylation in E. coli, play
      a key role for recognition by LeuRS. Results suggest that the recognition style
      of yeast class II tRNA is substantially different from that of E. coli.

PMID- 9586117
TI  - Characteristic distribution of bases and codons around the initiation and
      termination codons in whole reading frames in bacteria and yeast genomes.
AB  - Recently the complete nucleotide sequence of the entire genome was determined for
      yeast and a few kinds of bacterium. To see characteristic features of base
      sequence in the cistron (actually the open reading frame, ORF) and in the regions
      around a cistron (ORF), the biases of appearance frequency of bases from the base
      ratio were studied statistically. In the regions before the base biases were
      observed. The characteristic base distribution patterns were similar to all the
      cases of bacteria, but different from yeast. The base biases are reflected on the
      appearance frequency of amino acids near the N-termini and C-termini of proteins.
      The characteristic biases found in the amino acid sequence of the N-terminal part
      of bacteria proteins are different from that in yeast proteins.

PMID- 9586118
TI  - Effect of nucleotide sequence and metal ions at the active site on a short
      ribozyme activation.
AB  - Leadzyme, CUGGGAGUCC, is a ribozyme that requires Pb2+. We have investigated
      effects of target sequences and metal ions on a catalytic reaction of the
      leadyzme. The leadzyme plays as a catalyst for one site cleavage of a mutant
      substrate, GGAC decrease GAGCCAG, and a wild-type substrate, GGACC decrease
      GAGCCAG. The addition of 25 microM Nd3+ in the presence of 25 microM Pb2+ led to
      significant increase in the cleavage yield for the mutant substrate. But this
      increase of the yield is less than that for the wild-type substrate. The result
      suggests that the effect of Nd3+ on the leadzyme reaction depends on substrate
      sequence.

PMID- 9586119
TI  - Poly(L-lysine)-graft-dextran copolymer is a novel stabilizer of triplex DNA(II):
      potassium-insensitive triplex formation.
AB  - Triple helix formation involving guanine-rich oligonucleotides is inhibited by
      physiological concentrations of potassium (K+). Using in vitro electrophoretic
      mobility shift assay (EMSA), we show that PLL-g-dex copolymer significantly
      stabilizes triplex structure at physiological levels of K+ that greatly inhibited
      triplex formation with a unmodified, guanine-rich oligonucleotide.

PMID- 9586120
TI  - Analysis for the subcellular distribution of oligonucleotide/lipid complexes.
AB  - We synthesized a lipoglutamide having tetraethylene glycol tails (PEG lipid), and
      prepared a DNA/PEG lipid complex. Observation by a confocal laser scanning
      fluorescence microscope showed that the oligonucleotide/PEG lipid complex
      distributed in cytoplasmic region. On the other hand, a
      oligonucleotide/lipofectin complex distributed in nucleus. Interactions of the
      oligonucleotide complexes with isolated nucleus were also investigated, and
      mechanisms of the subcellular distributions were discussed.

PMID- 9586121
TI  - Aminoacyl-tRNA synthesis in Archaea.
AB  - The mechanism of aminoacyl-tRNA synthesis differs substantially between Archaea,
      Bacteria and Eukarya. Sequencing of archaeal genomes has suggested that the
      asparaginyl-, cysteinyl-, glutaminyl- and lysyl-tRNA synthetases are absent from
      a number of organisms in this kingdom. The absence of the asparaginyl- and
      glutaminyl-tRNA synthetases is in agreement with the observation that Asn-tRNA
      and Gln-tRNA are synthesized by tRNA-dependent transamidation of Asp-tRNA and Glu
      tRNA respectively in the archaeon Haloferax volcanii. Biochemical and genetic
      studies have now shown that while the cysteinyl- and lysyl-tRNA synthetases are
      present, the enzymes responsible for these activities are unique to Archaea.

PMID- 9586122
TI  - Activities of tRNA-embedded dimeric minizymes.
AB  - Ribozymes have been shown to be potent inhibitors of gene expression and viral
      function. Effects of ribozyme-mediated repression to target gene in living cells
      are correlated with the amounts of expression and stabilities of ribozyme
      molecules. In our previous study, it was demonstrated that a minimized hammerhead
      ribozyme, minizyme, with high activity forms a dimeric structure with a common
      stem II. We constructed dimeric minizymes that could cleave the BCR-ABL chimeric
      (b2a2) mRNA which had been difficult target for conventional hammerhead ribozymes
      without damaging the normal ABL mRNA. In order to achieve high expression of
      these dimeric minizymes in vivo for the treatment of CML, we embedded the dimeric
      minizyme portion downstream of a tRNA(Val) promoter sequence which could be
      recognized by RNA polymerase III. We determined cleavage activities of tRNA
      embedded dimeric minizymes and compared the activities between tRNA-embedded
      hammerhead ribozyme and tRNA-embedded dimeric minizymes. All tRNA-embedded
      dimeric minizymes tested were capable of cleavage the target substrate. The
      activity of the tRNA-embedded dimeric minizyme targeted at BCR-ABL mRNA was
      almost the same as that of the naked dimeric minizymes. Interestingly, the
      cleavage activity of tRNA-embedded dimeric minizymes was higher than that of tRNA
      embedded conventional hammerhead ribozyme.

PMID- 9586123
TI  - Structure-activity correlation for an HDV ribozyme composed of three RNA strands.
AB  - Hepatitis delta virus (HDV) RNA ribozyme system which consists of three RNA
      oligomer strands (substrate 8-mer; enzyme 16-mer plus 35-mer, Fig. 1) was
      designed. Effects of Mg2+ concentration on the pseudo first-order rate constant
      (kobs) of RNA cleavage reaction and on conformation of ribozyme complex were
      examined. The secondary structure of the complex was also analyzed by limited
      digestion with ribonucleases. The kobs and CD data were analyzed by curve-fitting
      analysis using equations derived for two-Mg2+ and three-Mg2+ ion binding models.
      The result revealed that a three-Mg2+ binding model can explain the Mg(2+)
      concentration-dependent changes of both conformation and activity of the HDV
      ribozyme.

PMID- 9586124
TI  - Selective recognition of tandemly repeated DNA sequences by homo- and
      heterodimers of short peptides.
AB  - The non-covalent and specific protein-protein interaction is critical to the
      specificity and the cooperativity of the DNA-binding by protein dimers. We have
      designed and synthesized three sets of peptide dimers with covalent- or
      noncovalent artificial dimerization modules to elucidate the structural and
      thermodynamic aspects for the sequence-specific DNA-binding by protein dimers. We
      have investigated the DNA binding of covalent dimer, noncovalent homodimer and
      noncovalent heterodimer with specific or nonspecific DNA sequences by gel
      mobility shift assay. Although the amino acid sequence of DNA-binding region of
      these peptide dimers are the same, the selectivity and the cooperativity of DNA
      binding by these peptide dimers were found to be different.

PMID- 9586125
TI  - Mechanism and intermediate for formation of 2'-deoxyoxanosine.
AB  - A reaction mechanism for the direct formation of 2'-deoxyoxanosine (dOxo) from 2'
      deoxyguanosine (dGuo) by nitrous acid (HNO2) or nitric oxide (NO) was explored by
      using guanosine (Guo) and its methyl derivatives. HNO2 treatment of 1
      methylguanosine (1-Me-Guo) indicated that the exocyclic amino nitrogen (N5) of
      dOxo originates from imino nitrogen (N1) of dGuo. A short-lived intermediate
      detected in the Guo-HNO2 system by reversed phase (RP) HPLC was converted into
      oxanosine (Oxo) and xanthosine (Xao) at neutral pH. Based on these findings, we
      discuss the reaction mechanism for the formation of dOxo.

PMID- 9586126
TI  - Analytical application of host-guest chemistry using in vitro selection.
AB  - A new bioassay system using oligodeoxyribonucleotides (DNAs) obtained by the in
      vitro selection method, instead of antibodies, is described. The DNAs which
      selectively bind to target molecules, folic acid, and thyroxine (T4), were
      selected. The DNAs were labeled with biotin or fluorescent molecules and the
      labeled DNA were used for detection of target molecules. The DNA strictly
      recognized the target molecules of which chemical structure is similar to each
      other.

PMID- 9586127
TI  - High-throughput synthesis of functionalized oligonucleotides.
AB  - Functionalization of oligonucleotides with fluorescent dyes, biotin, and other
      reporter and capture labels is efficient, reliable, and convenient on the ABI
      3948. The entire process of sequence entry, oligonucleotide synthesis, cleavage,
      deprotection, purification, quantitation, and sample collection is automated. Up
      to 48 oligonucleotides can be produced during unattended operation. The OneStep
      columns are filled with a mixture of nucleoside-loaded and underivatized, high
      cross link, non-swelling polystyrene beads to conduct both synthesis and
      purification. Real-time, quantitative PCR, FRET hybridization, sequencing and
      genetic analysis experiments show the positive performance effects of the
      combined synthesis and purification of fluorescent dye-labelled primers and
      probes.

PMID- 9586128
TI  - Removing tRNA from a cell-free protein synthesis system for use in protein
      production.
AB  - The cell-free system for biosynthesis of proteins is becoming an important tool
      for protein engineering. In particular, introduction of the unnatural amino acids
      is achieved though cell-free protein synthesis with the use of chemically
      acylated tRNA that recognizes a specific codon. In the original method, however,
      it was difficult to control the system through changing tRNA composition, as the
      endogenous tRNAs are involved in the reaction. Thus, in the present study, we
      digested the tRNA within Escherichia coli S30 extract with resin-bound RNase A,
      and estimated the protein synthesis activity. It was revealed that this digestion
      process does not damage the activity, if a protease inhibitor,
      phenylmethylsulfonyl fluoride (PMSF), is present in the digestion reaction.

PMID- 9586129
TI  - Novel DNA detection system of flow injection analysis (2). The distinctive
      properties of a novel system employing PNA (peptide nucleic acid) as a probe for
      specific DNA detection.
AB  - In order to realize immediate detection of a double stranded DNA amplified by
      Polymerase Chain Reaction (PCR), we applied Peptide Nucleic Acid (PNA) to the
      probe of DNA detection system using Surface Plasmon Resonance (SPR). We report
      our success in immediate detection of PCR products solution with high sequence
      specificity.

PMID- 9586130
TI  - Prevalence of antibodies to bovine virus diarrhoea virus and other viruses in
      bulk tank milk in England and Wales.
AB  - Bulk tank milk samples from 1070 dairy herds in England and Wales were tested by
      ELISA for antibodies to bovine virus diarrhoea virus (BVDV). A subset of 341
      herds was tested by ELISA for antibodies to bovine herpesvirus 1 (BHV-1), bovine
      respiratory syncytial virus (BRSV) and bovine coronavirus (BCV). None of the
      herds had less than 40 dairy cows and none had been vaccinated against BVDV. The
      prevalence of BVDV antibody-positive herds in the national population was
      estimated at 95 per cent and approximately 65 per cent of the herds had a high
      level of bulk tank antibody suggestive of recent infection with BVDV. Dairy herds
      in East Anglia and the south-east of England had a significantly lower risk of
      being BVDV antibody-positive than herds in the rest of England and Wales.
      However, these regional differences tended to diminish with increasing herd size.
      Around 69 per cent of the herds were BHV-1 antibody-positive and all the herds
      were antibody positive to BRSV and BCV. Comparison with earlier serological
      surveys revealed that there had been little change in the prevalence and
      distribution of BVDV antibody-positive herds in England and Wales over the last
      20 years, but that there had been an increase in the prevalence of BHV-1 antibody
      positive herds.

PMID- 9586131
TI  - Activation of extracellular matrix metalloproteinases in equine laminitis.
AB  - Samples of connective tissue obtained from the hoof of six laminitic and eight
      non-laminitic adult horses were analysed zymographically to investigate whether
      connective tissue matrix metalloproteinases are activated or induced during
      laminitis. The activity or matrix metalloproteinases was substantially greater in
      the tissues from the laminitic horses than in the tissues from the non-laminitic
      horses. A comparison of the collagenolytic activity in the laminitic and control
      tissues showed that collagenolytic activities corresponding to the 92 kDa (P <
      0.001), 72 kDa (P < 0.01) and 66 kDa (P < 0.01) bands were induced in the
      laminitic tissues.

PMID- 9586132
TI  - Pharmaceutical quality of anthelmintics sold in Kenya.
AB  - Nine anthelmintic products in pharmacies and from agricultural merchants in Kenya
      were tested for pharmaceutical quality. The concentration of active drug was
      compared with the claim on the label, and the variability of several products was
      tested between batches and between bottles within the same batch. All the
      products purchased claimed to contain levamisole but its mean (sd) concentration
      varied from 0 to 118.0 (13.3) per cent of the claimed. The concentration of
      levamisole in different batches of the same product ranged from 0 to 85.4 per
      cent of that claimed. One product consisting in part of mebendazole was found to
      contain 73.2 (9.4) per cent of the claimed concentration of this active component
      and two products consisting in part of oxyclozanide were found to contain 106.0
      (14.4) and 120.6 (6.1) per cent of the expected concentration of oxyclozanide.

PMID- 9586133
TI  - Treatment of infectious arthritis of the radiocarpal joint of cattle with
      gentamicin-impregnated collagen sponges.
AB  - Gentamicin-impregnated collagen sponges were used successfully in the treatment
      of chronic septic arthritis of the radiocarpal joint in two cattle. Both animals
      were moderately to severely lame and refractory to systemic antibiotics, and one
      of them was refractory to joint lavage and local antibiotics. The clinical
      diagnosis was confirmed by radiography and arthrocentesis. Arthroscopy was
      performed under general anaesthesia and, after debridement and lavage of the
      joint, gentamicin-impregnated collagen sponges were placed intra-articularly.
      Synovial fluid was sampled at 10 and 20 days after surgery and radiographs were
      taken three months (case 1) and two months (case 2) after surgery. The infection
      was eliminated from both animals and they recovered without residual lameness.

PMID- 9586134
TI  - Superovulatory response in beef cows following removal of the largest ovarian
      follicle.

PMID- 9586135
TI  - Anatomical abnormalities of the skull of a pink pigeon (Columba mayeri).

PMID- 9586136
TI  - Staffing at veterinary schools.

PMID- 9586137
TI  - Cat castrations and veterinary nurses.

PMID- 9586138
TI  - Cat castrations and veterinary nurses.

PMID- 9586139
TI  - Cat castrations and veterinary nurses.

PMID- 9586140
TI  - Changes to the Veterinary Laboratories Agency.

PMID- 9586141
TI  - Tail-biting and tail-docking in pigs.

PMID- 9586142
TI  - Tail-biting and tail-docking in pigs.

PMID- 9586143
TI  - Tail-biting and tail-docking in pigs.

PMID- 9586144
TI  - Management and the hour of parturition in mares.

PMID- 9586145
TI  - [100 years of scientific psychiatry. Sigmund Freud, Emil Kraepelin, Emile
      Durkheim and modern psychiatry].

PMID- 9586146
TI  - [Leptin--an interim evaluation].
AB  - The discovery of leptin, the product of the obese (ob)-gene, has broadened the
      horizons of research on energy balance. This hormone, produced and secreted by
      adipose tissue and some placental cells, finds its way to the hypothalamus, where
      it binds to the leptin receptors and signals satiety through the neuroendocrine
      axis. The fact that adipose tissue is not merely a storage depot, but also an
      important endocrine tissue, has revived the interest in the "lipostatic" theory
      of body fat regulation and has initiated many research efforts in the field of
      obesity, anorexia nervosa, bulimia, reproduction and haematology.

PMID- 9586147
TI  - Plasma catecholamines, atrial natriuretic peptide and blood lactate responses
      during upright bicycle ergometry with incremental steps adapted to individual
      maximal work capacity.
AB  - To assess whether hormone and metabolic responses in an upright bicycle exercise
      test are equivalent for subjects with different physical characteristics if test
      duration for reaching individual maximal work capacity (PWCmax) is standardized
      we investigated plasma catecholamines, human atrial natriuretic peptide (hANP)
      and blood lactate responses in twenty healthy sedentary subjects. Ten male (38.5
      +/- 4.7 yrs) and ten female (34.5 +/- 6.4 yrs) healthy volunteers performed two
      ergometries, a first one with incremental steps of 25 Watts each for two minutes
      to determine PWCmax, and a second one with incremental steps of PWCmax/6.
      According to this definition a test duration of 12 min was attained for all
      subjects for the second ergometry. The results show that the increase of the rate
      pressure product (RPP) as an index of relative cardiac work is significantly
      different between the male and female group in the test with constant 25 Watts
      steps. But with the modified exercise test RPP/time-slopes are nearly identical,
      identicating equivalent cardiac work due to gender and body surface. Similar
      results are obtained for plasma catecholamines, hANP and blood lactate. Mean
      values did not differ in the modified exercise test between the male and female
      group either in the sub-maximal range or at PWCmax. In conclusion, our data
      suggest that in a maximal exercise test with equal test duration, and considering
      individual physical properties for the calculation of incremental steps hormonal
      and metabolic responses are equivalent. It seems that the designed, modified
      exercise test provides inter-individual comparisons at least for these
      investigated parameters. The test may be helpful if catecholamines, hANP or
      lactate are used as diagnostic parameters in patients.

PMID- 9586148
TI  - Changes in thyroid hormones and lipids in endurance trained volunteers during
      acute and rigorous bed rest conditions.
AB  - The aim of this study was to evaluate the effect of an acute rigorous bed rest
      (ABR) (abrupt confinement to a rigorous bed rest regimen) and a rigorous bed rest
      (RBR) regimen on serum concentrations of thyroid hormones and lipids. The studies
      were done during seven days of a pre bed rest period and during seven days of an
      ABR and RBR period. Thirty endurance trained male volunteers aged 22 to 26 years
      with a peak oxygen uptake of 66.0 mL.min-1.kg-1 and running an average of 14.0
      km.day-1 were chosen as subjects. They were divided equally into three groups:
      (one) ten athletes placed under ambulatory conditions served as ambulatory
      control subjects (ACS), (two) ten athletes subjected to an acute rigorous bed
      rest regimen served as acute bed rested subjects (ABRS) and (three) ten athletes
      submitted to a rigorous bed rest regimen served as rigorous bed rested subjects
      (RBRS). For the simulation of the effect of ABR the ABRS group was submitted
      abruptly to a rigorous bed rest regimen. They did not have any prior knowledge of
      the exact date and time when they would be asked to submit to the RBR. For the
      simulation of the effect of RBR the RBRS group was subjected to a rigorous bed
      rest regimen on a predetermined date and time known to them right from the start
      of the study. During the pre bed rest period and during the ABR and RBR periods
      serum concentrations of thyroxine (T3), triiodothyronine (T4), thyroid
      stimulating hormone (TSH), cholesterol, triglycerides, total protein and albumin
      were measured. In the ABRS and RBRS groups serum concentrations of T3, T4, TSH,
      cholesterol, triglycerides, total protein and albumin increased significantly
      when compared with the ACS group. Serum concentrations of thyroid hormones and
      lipids in the ABRS group increased much faster and were more pronounced than in
      the RBRS group. It is concluded that exposure to RBR and, especially, to ABR
      conditions induces significant increases in serum concentrations of thyroid
      hormones and lipids. These changes occurred much earlier and were much greater in
      the ABRS group than in the RBRS group.

PMID- 9586149
TI  - [Epidemiology and clinical value of true umbilical cord knots].
AB  - OBJECTIVE: To evaluate the epidemiology of true knots of the umbilical cord and
      their impact on pregnancy outcome. MATERIALS AND METHODS: 22531 singleton
      deliveries were included in this retrospective study (1976-1994). Newborns with
      malformations were excluded. The database of the 2nd Department of Obstetrics and
      Gynaecology, Vienna University Hospital was analyzed. RESULTS: The incidence of
      true knots was 1.27% (n = 286). Multiparous women are more likely to give birth
      to a child with a true knot of the umbilical cord than primiparae (1.52% vs.
      1.01%, P < 0.001). Male fetuses are more frequently affected than females (1.49%
      vs. 1.04%, P = 0.01). Duration of pregnancy, fetal weight, presentation and mode
      of delivery are not significantly influenced by umbilical knots. Fetal acidosis
      (pH < 7.10) was more common in the cohort with true knots as compared with the
      controls (8.33% vs. 4.03%, P < 0.01). Apgar score and transfer rate to a neonatal
      unit were not influenced. Still-births were more common in the cohort with
      umbilical knots (1.7% vs. 0.6%, P < 0.05); there was no neonatal death in the
      cohort with true knots, however. CONCLUSION: A fetus with a true knot of the
      umbilical cord is at risk for fetal death. During labour umbilical knots have no
      adverse effect on pregnancy outcome.

PMID- 9586150
TI  - [Marfan syndrome: prevalence and natural course of cardiovascular
      manifestations].
AB  - The Marfan syndrome is an autosomal dominant disorder of the connective tissue
      with mutations on the fibrillin-1 gene encoding for fibrillin, a major component
      of the extracellular microfibrils. The prevalence of the syndrome is 7
      17/100,000. The mean life expectancy for untreated patients with Marfan syndrome
      is 32 years with aortic dissection, aortic rupture or cardiac failure due to
      mitral and aortic valve regurgitation as the predominant cause of death in > 90%
      of the cases. In severely affected cases with neonatal Marfan syndrome, patients
      are likely to survive only a few months. According to the literature database the
      prevalence of aortic dilatation is 76%, 26% for aortic regurgitation, 62% for
      mitral valve prolapse, and 29% for mitral valve regurgitation in adult patients
      with classic Marfan syndrome. Pathogenesis and the natural cause of each
      cardiovascular manifestation is thoroughly discussed with the problems resulting
      from associated cardiac arrhythmias, sudden cardiac death, endocarditis, and less
      frequent cardiovascular manifestations of the Marfan syndrome. Special focus is
      placed on the analysis of cardiovascular complications during pregnancy.

PMID- 9586151
TI  - [Marfan syndrome: diagnosis of cardiovascular manifestations].
AB  - With the availability of modern imaging modalities such as magnetic resonance
      imaging (MRI), contrast-enhanced computed tomography (CT), and transesophageal
      echocardiography (TEE), diagnostic options in the evaluation of Marfan patients
      have been improved profoundly. The most recent diagnostic advances comprise
      noninvasive tissue characterization of the aortic wall, immunofluorescence
      studies or pulse chase analyses of skin and cultured dermal fibroblasts, and
      molecular analysis at the cDNA/DNA level of the fibrillin-1 gene. New diagnostic
      insights have eventually led to revised nosologic criteria for the diagnosis of
      Marfan syndrome. The diagnostic reliability as well as the advantage and
      limitation of these recent diagnostic strategies are discussed; moreover
      diagnostic concepts for patients with neonatal as well as classic Marfan syndrome
      are presented and discussed in the context of the clinical management during
      adolescence, gravidity as well as in the pre- and postoperative patient.

PMID- 9586152
TI  - [Marfan syndrome: therapy of cardiovascular manifestations].
AB  - With optimal clinical management of patients with Marfan syndrome, life
      expectancy may be improved substantially from 32 years to a nearly normal life
      span. Cornerstones of clinical management comprise genetic counseling, life-style
      management, and cardiovascular surveillance, which includes regular aortic
      imaging and endocarditis prophylaxis. Prophylactic use of beta-blocking agents as
      well as timing of elective surgery and the choice of the optimal surgical
      technique are difficult issues that obviously need to be individualized. Juvenile
      or postoperative patients as well as pregnant patients with Marfan syndrome pose
      particular problems. This review intends both to facilitate differential decision
      making based on referenced evidence and to provide guidelines for therapeutic
      strategies. Finally, a review of the most recent advances to somatic gene therapy
      is given.

PMID- 9586153
TI  - [Initial clinical results with the Amplatzer septal occluder--a self-centering
      double disc for occlusion of atrial septal defects].
AB  - In recent years many different systems for transcatheter closure of an atrial
      septal defect (ASD) have been developed and tested. However, all systems
      presently available have some special disadvantages. The recently introduced
      Amplatzer Septal Occluder (ASO), though, appears promising. It is a self
      expanding and self-centering double disc made from a Nitinol mesh, which is
      tightly woven to give mechanical strength. Both discs are separated by a
      connecting cylindrical portion. Its diameter may be chosen, so that it
      corresponds to that of the ASD. Discs of polyester patches are sewn into the
      retention discs as well as into the cylindrical portion of the device in order to
      augment thrombogenicity. After measuring the diameter of the ASD with a balloon,
      an appropriate ASO is selected and advanced into the left atrium through a 7 or 8
      French sheath. Then the distal disc and part of the connecting cylindrical
      portion is developed in the left atrium and pulled against the atrial septum, so
      that the cylindrical portion is occluding the ASD. Thereafter, proximal disc is
      deployed and the delivery cable disconnected. As long as the cable is connected
      to the device repositioning is easily achieved by pulling the device back into
      the sheath. Within a time period of 4 months in 29 out of 31 patients (median
      age: 12.1 years, median weight: 45.0 kg) complete closure of the ASD with a mean
      diameter of 11.0 mm (6-20 mm) was achieved without complications, the average
      fluoroscopy time being 8.3 min (2.9-21.5 min). Mean Qp:Qs was 1.5 (0.9-2.2).
      During a mean follow-up period of 2.1 months post implantation fixed seating of
      the ASO without residual shunt, arrhythmias, thrombembolic events and impairment
      of A-V valves was observed in all patients. CONCLUSION: The Amplatzer septal
      occluder allows quick, safe, and complete closure of atrial septal defects
      without complications if one adheres to strict implantation criteria. For a final
      judgement, however, long-term follow-up studies are necessary.

PMID- 9586154
TI  - [Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive
      cardiomyopathy: acute results in 66 patients with reference to myocardial
      contrast echocardiography].
AB  - BACKGROUND: In hypertrophic obstructive cardiomyopathy (HOCM) therapy, surgical
      myectomy and DDD pacemaker implantation are considered to be established
      extensions to medical treatment. As an alternative procedure for reducing the
      left ventricular outflow tract gradient (LVOTG), percutaneous transluminal septal
      myocardial ablation (PTSMA) by alcohol-induced septal branch occlusion has been
      introduced. We report on the acute results and the short-term clinical course
      following 66 PTSMA interventions in symptomatic patients (pts.) with HOCM.
      METHODS: In pts. who were symptomatic despite adequate drug therapy (31 women, 35
      men; mean age 52.9 +/- 15.0 years, range: 16-86) 66 PTSMA interventions were
      performed (4 pts. with a re-intervention). Septal branches were occluded by
      injection of 3.5 +/- 1.8 (1.5-11.0) ml ethanol (96%). In the first 30 pts. the
      target vessel was determined by probatory balloon occlusion (PBO) alone, in the
      following 36 by additional myocardial contrast echocardiography (MCE). In
      hospital follow-up of LVOTG and clinical course were determined. RESULTS: The
      invasively determined LVOTG could be reduced by > 50% or eliminated in 54
      interventions (82%) with a mean reduction from 71.2 +/- 34.4 (4-174) to 18.0 +/-
      21.5 (0-105) mmHg at rest and from 145.7 < or = 42.3 (68-257) to 63.7 +/- 49.3 (0
      185) mmHg post extrasystole (p < 0.0001). All pts. experienced angina pectoris
      within the first 24 hours. The creatine kinase peak was 690 +/- 364 (201-1810)
      U/l after 11.0 +/- 5.4 (4-24) hours. 45 pts. (68%) developed trifascicular block,
      requiring temporary, or in 9 cases (14%) permanent, (DDD) pacemaker implantation.
      Two pts. (3%) died 9 and 2 days after successful intervention, due to
      uncontrollable ventricular fibrillation associated with betasympathomimetic and
      theophylline treatment for chronic obstructive pulmonary disease in one case, and
      fulminant pulmonary embolism in the other. The remaining pts. were discharged
      after 11.1 +/- 4.6 (5-24) days following an uncomplicated hospital course. The
      introduction of MCE was associated with a higher percentage of short-term success
      (92% vs. 70%, p < 0.015). CONCLUSIONS: PTSMA in HOCM is a promising non-surgical
      technique for septal myocardial reduction with a consecutive reduction of the
      LVOTG. MCE has shown to be a useful addition to PBO for selection of the target
      vessel. Possible complications are trifascicular blocks requiring permanent
      pacemaker implantation and tachycardiac rhythm disturbances. Prospective, long
      term observations of larger populations and a comparison with the established
      forms of therapy are necessary in order to determine the definitive significance
      of PTSMA.

PMID- 9586155
TI  - ["Cox/Maze-III operation" as surgical therapy of chronic atrial fibrillation
      during mitral valve and atrial septal defect II operation].
AB  - PROBLEM: Atrial fibrillation is associated with significant morbidity and
      mortality. The increased risk of thromboembolism makes constant anti-coagulation
      necessary, while the absence of atrial contraction worsens the hemodynamic
      situation. In this study we examined the results of simultaneous surgical
      treatment of chronic atrial fibrillation through "Cox/Maze-III-procedure" while
      mitral valve surgery and atrial septal closure. PATIENTS AND METHODS: Between
      February 1995 and July 1997 sixteen patients aged 50 to 72 y (mean: 59 y)
      underwent open heart surgery (mitral valve replacement n = 10, reconstruction n =
      3; mitral valve reconstruction and atrial septal closure n = 1, atrial septal
      closure n = 1, thrombectomy from left atrium n = 1) and "Cox/Maze-III-procedure"
      in one session. Preoperative duration of chronic atrial fibrillation was between
      2 and 12 y (mean: 5.0 y). The patients were examined preoperatively and
      postoperatively 3, 6, 12, and 24 months after surgery using the following
      methods: transesophageal echocardiography (TEE), ECG, long-term ECG, and stress
      ergometry. RESULTS: During the early postoperative period (< 7 d) all of the
      patients were in sinus rhythm or atrial pacing; eight patients intermittently had
      atrial fibrillation. In the follow-up period from 1 to 27 months (mean 14
      months), 15 patients have a stable sinus rhythm (94%). One patient,
      preoperatively known to have intermittent tachybradycardia, received a pacemaker
      2 months postoperatively for sinus bradycardia. Postoperatively in TEE patients
      showed left atrial contraction with improvement of hemodynamic situation. Stress
      ergometry 6 months postoperatively showed lower increasements of heart rate, at
      12 months normal frequency. CONCLUSION: The surgical treatment of chronic atrial
      fibrillation through "Cox/Maze-III-procedure" can be performed combined with
      other heart operations without increased perioperative or postoperative risks.
      The Maze-procedure is an effective surgical therapy of chronic atrial
      fibrillation. Postoperatively there is an improvement of the hemodynamic
      situation because of sinus rhythm and synchrone atrioventricular contraction.

PMID- 9586156
TI  - [Heart transplantation in infancy: experiences at the Giessen Pediatric Heart
      Center].
AB  - From June 1988 to December 1996 heart transplantations were performed in 36
      newborns and infants below one year of age. Diagnosis were hypoplastic left heart
      syndrome (n = 26), endocardial fibroelastosis (n = 4), cardiomyopathy (n = 3),
      and other complex congenital heart defects (n = 3). Mean waiting time for
      transplantation was 52 days, the mean donor-recipient bodyweight ratio was 1.8.
      Seven patients (19%) died after transplantation mainly within the first month
      after transplantation. The cumulative probability of survival is 79% in all
      patients. The influence of increasing experience is indicated when patients
      transplanted from 1988-1993 (n = 15) are compared with transplants from 1994-1996
      (n = 21). The overall survival in the first group was 50%, whereas patients
      transplanted from 1994 showed a probability of survival of 92%. The 1-year
      survival rate in the later group was 100%. In 20 patients a total of 31 rejection
      episodes were observed. 2 infants died due to rejection. 71% of all rejections
      occurred during the first month after transplantation. Renal function was
      slightly impaired one year after transplantation in all patients without tendency
      for deterioration in the sequel. The somatic development is normal in nearly all
      infants and the quality of life is excellent. All infants live at home without
      any restrictions. Two patients, however, suffer from a neurologic deficit. Until
      now there is no evidence of coronary vascular disease or malignancy. Heart
      transplantation is in our opinion a reconsiderable alternative in the treatment
      of complex cardiac disease and cardiomyopathy in infants.

PMID- 9586157
TI  - [Magnetic resonance tomography in diagnosis of cardiac space-occupying lesions].
AB  - Imaging of cardiac masses is technically highly demanding. Imaging techniques
      should fulfill the following requirements: excellent spatial and temporal
      resolution, short imaging time, broad availability, low cost. Diagnostic
      questions include: tumor origin, size, extension, tissue type, functional
      consequences of tumor involvement. Transthoracic echocardiography is the imaging
      technique of choice in most patients. If clinical questions remain, TEE, CT or
      MRI can be used as secondary imaging techniques. Advantages of MRI include:
      excellent spatial and temporal resolution, multiplanar capabilities, large field
      of view, lack of radiation. Pericardial and intracardiac as well as paracardiac
      masses are depicted in great detail and therapeutically relevant information is
      usually obtained in addition to what is known from echocardiography. Although
      tissue differentiation is possible, a histologic diagnosis cannot be obtained.
      Disadvantages of MRI are artifacts in patients with severe arrhythmias or
      dyspnoea.

PMID- 9586158
TI  - [Electro-anatomic mapping of the sinoatrial activation: initial experiences with
      the new CARTO mapping system].
AB  - Prerequisite for successful radiofrequency catheter ablation on tachycardias is
      the exact mapping during the electrophysiologic study. The new mapping system
      CARTO allows a three-dimensional color-coded electroanatomic map of impulse
      propagation using electromagnetic technology. Mapping of sinuatrial activation in
      the right atrium of 11 patients represents the first clinical experience with
      this new system. The physiological activation sequence could be determined in all
      patients three-dimensionally, and the sinus node could be localized as a
      physiological activation focus with interindividual variability only in the
      sagital plane without complications. The nonfluoroscopic mapping system allows
      high resolution visualization of electrical activity and may therefore improve
      precision and simplify the determination of the arrhythmogenic substrate during
      tachycardias for successful catheter ablation.

PMID- 9586159
TI  - [Bypass perforation by stent implantation: complication management. A case
      report].
AB  - We describe a case-report on an perforation of an aorto-coronary venous bypass
      graft, a complication induced by a stent-implantation. Perforations of coronary
      arteries are rare, however, for interventional cardiologists well-known
      complications. This case report is of special interest (1) because the
      perforation did not occur in a coronary artery but rather in an eight year old
      venous bypass graft and (2) because the perforation was induced by a stent
      implantation. In addition, this case report describes in great detail the
      management of vessel perforation: several invasive methods contributed to
      minimize pericardial effusion and to stabilize the patient until surgical
      revision could be performed.

PMID- 9586160
TI  - [Cardiology between research and the clinic. 63rd Annual Meeting of the German
      Society of Cardiology, Mannheim, 3-5 April 1997].

PMID- 9586162
TI  - [Diagnosis and therapy of acute diverticulitis].

PMID- 9586164
TI  - Our experience in surgical treatment of diverticula of the colon.

PMID- 9586163
TI  - [Therapeutic aspects of diverticular disease from the surgical viewpoint over
      time].

PMID- 9586165
TI  - [Laparoscopic surgery of sigmoid diverticulitis].

PMID- 9586166
TI  - [Surgical therapy of sigmoid diverticulitis: can resection with primary
      anastomosis be considered the current standard procedure? Results of 65
      patients].

PMID- 9586167
TI  - [Therapy of diverticulitis of the large intestine--reliable and controversial
      aspects].

PMID- 9586169
TI  - [Inflammation of the colorectum--role of pathology in preoperative and
      postoperative diagnosis of chronic inflammatory bowel diseases].

PMID- 9586168
TI  - [Differentiated procedure in colonic diverticulitis].

PMID- 9586170
TI  - [Dysplasia-carcinoma sequence in chronic inflammatory bowel diseases].

PMID- 9586171
TI  - [Management of the chronically ill patient with Crohn disease and ulcerative
      colitis].

PMID- 9586172
TI  - Restorative proctocolectomy and ileal pouch in surgical treatment for ulcerative
      colitis.

PMID- 9586173
TI  - Postoperative hernias in the site of colostomy.

PMID- 9586174
TI  - Crohn's disease in perspective of our own experience.

PMID- 9586175
TI  - [Surgical therapy of Crohn disease and strategies in previously operated
      patients].

PMID- 9586178
TI  - [The intestine as the central organ in the development of multiple organ failure
      after severe trauma--pathophysiology and therapeutic approaches].
AB  - Multiple organ failure is with an incidence of 10-25% and a mortality of 50-70%
      the most severe complication after severe trauma. Intestinal ischemia and a
      corresponding impaired gut barrier function is thought to have a high impact on
      the development of multiple organ failure after severe trauma. Under normal
      conditions the intestinal wall is a sufficient barrier against bacteria and their
      products. Gut ischemia is followed by mucosal lesions, the intestinal
      permeability is increased. Translocating bacteria and bacterial products
      (endotoxin, peptidoglykan) can lead to a local and/or systemic immun-inflammatory
      response, which is made responsible for the development of multiple organ
      failure. Tonometry as a possibility of monitoring intestinal ischemia as well as
      a tool to estimate the prognosis of multiple trauma patients is still discussed
      controversially. Dopexamin, which directly influences intestinal ischemia (goal
      directed therapy) might be a successful treatment option, however until now no
      clinical study about beneficial effects of dopexamine in severely injured
      patients is available. Selective gut decontamination showed no clinical benefits
      in multiple trauma patients. Early enteral nutrition especially with
      immunomodulating ingredients ("immunonutrition") decreases posttraumatic
      complications as well as the incidence of MOF. However a reduction of mortality
      could not be described in severely injured patients so far.

PMID- 9586179
TI  - [Clinical effects of childbirth with median episiotomy and anal sphincter injury
      on fecal incontinence of primiparous women].
AB  - Obstetric damage of the anorectal continence organ can lead to impaired anal
      continence. To assess the effect of birth, either with or without direct injury
      of the anal sphincter, 123 primiparae were studied. 41 patients with a midline
      episiotomy and 82 patients with an additional injury of the anal sphincter were
      assessed at a median of 21 weeks postpartum and compared with 18 healthy
      volunteers. Anorectal manometry as well as a standardized questionnaire were
      employed. Patients with an additional injury of the anal sphincter reported
      persistent flatus incontinence significantly more often (p = 0.0069) than
      patients with a midline episiotomy only. Incontinence of solid or liquid stool
      occurred only transiently. Compared to nulliparae in all primiparae a significant
      shortening of anal canal and a decreased squeeze pressure were observed. In
      addition, a significantly reduced resting pressure was seen in patients with an
      anal sphincter injury. The rectoanal inhibitory reflex was absent significantly
      more often following anal sphincter tear (p = 0.0023). Vaginal delivery, both
      with and without anal sphincter injury, leads to early detectable changes in
      anorectal sphincter function.

PMID- 9586180
TI  - [Value of electrotherapy within the scope of conservative treatment of anorectal
      incontinence].
AB  - The following study reports on transanal electric stimulation as a conservative
      method of treatment in anal incontinence. In the centre of interest are clinical
      examinations on 45 patients that underwent a combined treatment with the IT
      system 100 from Reha-Medi and pelvic floor training. A collective of 29 patients
      only treated with pelvic floor training was used as a control group. The results
      were based on a thorough medical history ascertainment and the corresponding
      clinical examinations at the beginning and end of the treatment. Our findings
      were classified according to the modified score of incontinence of Holschneider
      [16]. After therapy 42.2% of patients with electric stimulation therapy and 27.6%
      of the control group showed continence. 40 respectively 62.1% were non responder
      without relevant benefit. In the electric stimulation group the median score
      before and after therapy amounted to 6.57 versus 9.24 points. The control group
      achieved 6.72 respectively 8.58 points. The differences are statistically
      significant (p < 0.05, Student t-test). Concerning the results in relation to the
      cause of the incontinence, no significant differences between idiopathic and
      traumatic origin of the insufficiency of the sphincter mechanism are found in
      both groups. Therefore all variations of anorectal incontinence are seen as
      indication for treatment. The international literature as well as our own results
      confirm that electric stimulation is effective and may be in special cases a
      major factor in the conservative treatment of anorectal incontinence.

PMID- 9586181
TI  - [How can the prognosis of acute mesenteric artery ischemia be improved? Results
      of a retrospective analysis].
AB  - AIM: Acute mesenteric ischemia is difficult to diagnose and is combined with a
      high mortality. In a retrospective analysis it was investigated how to improve
      the poor prognosis of the disease. PATIENTS AND METHODS: Between January 1988
      through December 1994 a total of 46 patients were operated on for acute
      mesenteric ischemia. Mesenteric artery occlusion was present in three quarters of
      the cases (n = 35). These were analysed according to symptoms, diagnosis,
      mechanism of occlusion, operative procedure and prognosis. Distribution of gender
      was almost balanced (19 women, 16 men) with a median age of 70.5 years. RESULTS:
      Embolic arterial occlusion was predominant (n = 22). Most frequently, the
      superior mesenteric artery was exclusively concerned (n = 22). Serum levels of
      lactate and leucocytes were preoperatively elevated in over 90% (median values:
      lactate 53 U/l, leucocytes 15050/ml). In 16 patients diagnosis was made on the
      ground of clinical parameters and/or angiography, but 19 patients were not
      diagnosed until operation. 19 patients were operated within 6 hours, 12 patients
      within 24 hours after admission (> 24 hours: n = 4). Vascular reconstructive
      procedures only, such as thrombectomy and/or aortomesenteric bypass were
      performed in 9 cases, in a further 7 cases combined with bowel resection. Bowel
      resection alone was done in 7 patients, 12 patients had only diagnostic
      laparotomy. 13 patients survived, 10 of them had been treated with vascular
      reconstruction. CONCLUSION: Acute mesenteric ischemia ought to be suspected in
      every patient with uncertain abdominal pain, because only early diagnosis can
      improve prognosis. Measurement of serum lactate is diagnostically helpful,
      although not proving. In case of elevated lactate levels and uncertain abdominal
      symptoms angiography of the mesenteric vessels should be performed early. At
      operation, blood flow in the mesenteric arteries should be restored whenever
      possible.

PMID- 9586182
TI  - [Longitudinal study of vascular patients with standardized Bruckner distal limb
      amputation].
AB  - OBJECTIVE: The present study aims to evaluate early and late results after
      standardized below-knee amputation according to Bruckner in vascular patients.
      PATIENTS AND METHODS: During the period 1982 to 1989 72 patients with occlusive
      arterial disease stage IV underwent below-knee amputation at an average age of
      69.7 years. 38 of the amputees could be re-investigated at the end of 1991 after
      an average follow-up of 5.3 years. Evaluation criteria consisted of wound
      healing, knee joint preservation, prosthetic fitting, stump appearance, gait
      capacity or ambulation, the need for assistance by another person and patients
      own valuation. Accordingly, rehabilitation level was classified to be good,
      satisfying or dissatisfying. RESULTS: Knee joint preservation rate amounted to
      91.7% (66 patients). Postsurgical prosthetic fitting could be achieved in 55
      amputees (76.4%). All the 38 re-investigated stumps were inapparent. 27 of the
      patients (71.1%) showed good and 7 patients (18.4%) satisfying rehabilitation,
      whereas the rehabilitation level was dissatisfying in 4 cases (10.5%). This
      objective evaluation was affirmed by patients own estimation: 33 amputees (86.6%)
      would again agree to the operation. CONCLUSIONS: Early as well as late results in
      this series indicate that the standardized below-knee amputation according to
      Bruckner promises high rates of healing, knee joint preservation and thus
      successful rehabilitation in patients with occlusive arterial disease.

PMID- 9586183
TI  - [Fiber optic measurements with the Bilitec probe for quantifying bile reflux
      after aboral stomach resection].
AB  - Nonphysiological alkaline reflux after partial gastrectomy may produce a range of
      gastrointestinal disorders. The Bilitec probe is a fibroptic sensor that, for the
      first time, makes in vivo measurement of this reflux possible, by assay of
      spectrophotometric absorption of bilirubin. We studied 20 patients who had
      undergone partial gastrectomy for benign peptic ulcer disease. Ten patients had
      Billroth II reconstruction and ten had Roux-en-Y reconstruction. In the Roux-en-Y
      Group we found almost complete control of symptoms and no objective evidence of
      alkaline reflux as measured by the Bilitec probe. In the Billroth II group we
      detected by the fiberoptic sensor significant bile reflux into the stomach
      remnant. Based on these results we recommend Roux-en-Y gastrojejunostomy as the
      method of choice for reconstruction after distal gastric resection.

PMID- 9586184
TI  - [Diagnosis and therapy of traumatic injury of the pancreas].
AB  - Traumatic injuries of the pancreas are with 3 to 12% of all abdominal traumas an
      uncommon finding. Intraabdominal combined injuries and unspecific symptoms make
      an early detection often difficult. In the present study we report on 25 cases
      (4.7%) with pancreatic trauma out of 529 abdominal injuries that were treated
      between 1973 and 1996. In 68% of the cases, we detected simple gland lesions with
      an A.A.S.T.-score I-III (American Association for the Surgery of Trauma). In 32%
      of the cases, we found extended ruptures of the head of the gland (score IV and
      V). These patients presented severe therapeutic problems. 98% of our patients had
      combined intraabdominal injuries. With respect to imaging techniques, CT-scan and
      ERCP were the most sensitive procedures. Our therapeutic management included in
      14 of the cases external drainage after debridement, 6 pancreatic head--and 3
      left resections. 2 patients had to undergo a duodenopancreatectomy. The morbidity
      in our study was 33% (8 patients), whereas septic complications were most often
      encountered. The clinical mortality was 24% (6 patients). Based on our results,
      simple drainage after selective debridement may be sufficient for simple gland
      contusions. For the treatment of severe damages of the pancreatic head, including
      lesions of the pancreatic or bile duct or duodenum, adequate resection methods
      are recommended. An early diagnosis is mandatory facilitated by regular
      employment of CT-scanning and ERCP techniques.

PMID- 9586186
TI  - [Department administration by the physician].

PMID- 9586185
TI  - [CT-controlled percutaneous drainage of intra-abdominal abscesses with basket
      catheters].
AB  - Today, CT-guided percutaneous drainage for intraabdominal abscesses of various
      origin and location is well accepted. With this method open surgery and its
      complications can be often avoided. We report results of such treatment in 47
      patients with intraabdominal abscess formation. 66 "basket" catheters were placed
      into abscess formations of differing sizes and locations. 27 patients had
      developed abscess formation after surgery, in 2 patients abscesses after
      tumorembolisation were drained. In 18 cases there was no previous surgery. No
      complications occurred. Mean drainage time was 8.5 days. Surgical intervention
      was avoided in 34/47 patients. 9 of 47 patients received only percutaneous
      drainage. 25 of 47 patients required concomitant antibiotics for successful
      treatment. Antibiotics were selected according to bacterial culture with
      resistance determination. 13/47 cases required secondary surgery. About 80% of
      intraabdominal abscesses are curable with CT guided percutaneous drainage and
      systemic antibiotic medication. If a percutaneous drainage fails and signs of
      infection still remain, the procedure can be repeated. If secondary surgery after
      failing of percutaneous drainage should become necessary, the extent of the
      surgical intervention can be reduced. Surgery is necessary, if CT guided
      percutaneous drainage could not reach the abscess formation, if drainage failed
      or if an additional illness exists, which requires an operation.

PMID- 9586187
TI  - [The so-called Spigelian hernia--a rare lateral hernia of the abdominal wall].
AB  - A patient with Spigelian hernia is presented and the main pathological and
      clinical features are discussed. Its true incidence is probably greater than the
      small number of patients reported in the literature due to failure to recognize
      the clinical picture. A hernia through a defect in the Spigelian fascia
      (aponeurosis of the transverse muscle of the abdomen) is called Spigelian hernia.
      The semilunar (Spigelian) line is defined as the line forming the transition from
      muscle to aponeurosis in the transverse muscle of the abdominal wall. It is a
      lateral convey line between the costal arch and the pubic tubercle. The part of
      the aponeurosis that lies between this semilunar line and the lateral edge of the
      rectus muscle is called the "Spigelian fascia" (correct: Spigelian aponeurosis).
      The hernia is located intramurally because the hernia is covered by the
      aponeurosis of the external oblique aponeurosis, so that both, the hernial sac
      and the orifice, can often not be detected by palpation. Clinical symptoms are
      not characteristic but most patients have a distinct tender point above the
      hernial orifice.

PMID- 9586188
TI  - [Value of computerized tomography in diagnosis of Boerhaave syndrome].
AB  - The mortality rate of spontaneous oesophageal rupture can be reduced by rapid
      diagnostic evaluation and early therapeutic intervention above all. We report on
      the prompt diagnosis of Boerhaave syndrome by thoracoabdominal CT scan and
      oesophagoscopy in a 75 year old female patient with false negative oesophagogram.
      The oesophageal rupture was transabdominally approached and closed by suture and
      a gastric fundus patch 6 hours after admission to the hospital. Pleural space
      lavage and drainage was done thru a left thoracotomy. The patient developed
      bronchopneumonia and sepsis and was discharged from the hospital 8 weeks post
      admission.

PMID- 9586189
TI  - [Primary malignant melanoma of the esophagus].
AB  - Primary malignant melanoma of the esophagus is extremely rare. Less than 200
      cases have been published worldwide up to now. We report a case of a 65-years old
      male suffering from dysphagia for four months. The endoscopy showed a polypoidal
      tumor of black colour in the distal part of the esophagus. The histological
      diagnosis of the initial biopsy specimen was melanoma. Partial esophagectomy and
      lymph node sampling were performed. The resected specimen showed a polypoid tumor
      with black pigmentation of 8 x 5 x 3 centimeter. Histopathology revealed a
      primary malignant melanoma of the esophagus stage pT2 pN1 M0 and grading three.
      The patient died 8 months after resection from general metastatic disease. Age,
      sex, symptoms, duration of symptoms and time of survival are similar as described
      in former cases.

PMID- 9586190
TI  - [Effect of forced organ cooling on microperfusion of donor livers].
AB  - With regard to the factors of graft damage the role of rapid cooling during cold
      in situ perfusion should not be underestimated. The aim of this study was to
      analyse the effect of rapid cooling on microperfusion of rat livers in an in
      vitro model. MATERIAL AND METHODS: During harvest of 14 rat livers the organs'
      core temperature was monitored. Two groups were formed: (1) cold UW perfusion.
      (2) cold UW perfusion under additional graft cooling by iced water. Thereafter,
      isolated livers were perfused (4 degrees C. 1 h, 5 mmHg) monitoring the
      portocaval resistance, and liver enzyme release and pH levels in the perfusate.
      Finally, portal angiography of each liver was performed. RESULTS: Rapid in situ
      cooling resulted in a decrease of the plateau temperature of the organ by 6.5
      degrees C (p < 0.01). The pH slope in the perfusate and the enzyme release were
      diminished obviously, but not significantly. On the other hand, the portocaval
      resistance was increased by more than 20% (p < 0.05). Portal angiographies
      assessed by a special score expressed a marked deterioration of microperfusion in
      peripheral and subcapsular regions. CONCLUSIONS: This study shows that rapid
      cooling results in worsened microperfusion of liver grafts. The effect of rapid
      cooling on function and histomorphology of transplanted livers should be analysed
      in further investigations.

PMID- 9586192
TI  - [Compartment syndrome--a medical expert case].

PMID- 9586191
TI  - [Intramuscular pO2 monitoring in compartment syndrome--an experimental study].
AB  - HYPOTHESIS: Measuring intracompartmental pressure is a well accepted method in
      evaluating a compartment syndrome, which may occur after limb ischemia followed
      by reperfusion. As a compartment syndrome is paralleled by a decreased
      microcirculation it should be possible to evaluate a compartment syndrome also by
      measuring intramuscular pO2. METHODS: Anesthetized rats (spontaneous breathing
      via tracheotomy) were subjected to infrarenal ligation of the aorta. A pressure
      catheter was placed subfascial in the crural muscle group of one hind limb,
      whereas the contralateral side was prepared with a pO2 catheter. Besides a sham
      operated group, three experimental groups were subjected to either 2 hrs, 4 hrs
      or 6 hrs of ischemia followed by 4 hrs of reperfusion. One further group was also
      subjected to 4 hrs of ischemia and 4 hrs of reperfusion but received a fasciotomy
      at the time of reperfusion. Compartment pressure and intramuscular pO2 were
      recorded every 15 min. For histological examination muscle specimen were obtained
      after each experiment. RESULTS: Two hours of ischemia followed by 4 hrs of
      reperfusion did not result in any morphological changes and also not in any
      significant change in compartment pressure during both phases, whereas pO2
      significantly dropped during ischemia (from 19.0 mmHg to 3.0-5.0 mmHg) and
      returned to normal during reperfusion. In prolonged ischemia (4hrs)
      morphologically a severe interstitial edema was evident, compartment pressure
      increased during reperfusion (from 2.0 mmHg to 8.8 mmHg) and pO2 dropped during
      ischemia down to 3.0 mmHg and did not return to normal during reperfusion (10.5
      mmHg versus 19.0 mmHg normal). In case of 6 hrs ischemia, partial necrosis and
      only little interstitial edema were found morphologically. There was no
      significant change in compartment pressure throughout the study; and pO2 remained
      significantly decreased even during reperfusion (2.0-3.0 mmHg). DISCUSSION:
      Normal compartment pressure could mislead to false negative interpretation of
      compartment syndrome, whereas pO2 clearly identifies the microcirculatory state
      of the muscle. Thus, intramuscular pO2 monitoring presents a valuable method in
      evaluating compartment syndrome, especially in case of suspect clinical signs but
      normal compartment pressure.

PMID- 9586193
TI  - [Laparoscopic splenectomy].
AB  - To date more than 400 laparoscopic splenectomies have been reported in the
      literature. The main indications for the procedure are benign haematological
      diseases, in particular idiopathic thrombocytopenic purpura. Laparoscopic
      splenectomy to treat malignant illnesses is rare and is usually restricted to
      small or only moderately enlarged spleens. Technically, the lateral abdominal
      approach with the patient in a right decubitus position has the advantage over
      the anterior approach in the supine patient of permitting better access to the
      organ. Under the force of gravity the stomach and intestines drop out of the
      operating field, and the splenic ligaments are placed under tension. This
      facilitates dissection with the harmonic scalpel and safe divisioning of the
      hilar vessels using the linear stapler. The individual steps of the procedure are
      described in detail.

PMID- 9586194
TI  - Cladobotryal: a fungal metabolite with a novel ring system.
AB  - In screening for antifungal metabolites a novel compound, cladobotryal, was
      isolated from the mycoparasitic fungus Cladobotryum varium. Its structure was
      established as (+)-(2R*,3R*)-2-[(Z)-2-buten-2-yl]-3, 7-dihydro-3-formyl-3-methyl
      5-phenylfuro[2,3-b]pyridin-4(2H)-one on the basis of spectroscopic evidence and
      single crystal X-ray analysis of its methyl hemiacetal. The fused furo[2,3
      b]pyridinone skeleton of cladobotryal seems unprecedented within the chemical
      literature.

PMID- 9586195
TI  - Synthesis of 11C/13C-labelled prostacyclins.
AB  - A one-pot synthesis of (15R)-16-(3-[11C]methylphenyl)-17,18,19, 20-tetranoriso
      carbacyclin methyl ester was performed using a palladium-promoted reaction of
      [11C]methyl iodide with (15R)-16-(3-tri-n-butylstannylphenyl)-17,18,19, 20
      tetranorisocarbacyclin methyl ester. The C-15 epimer (15S)-16-(3
      [11C]methylphenyl)-17,18,19,20-tetranorisocarbacyclin methyl ester was
      synthesised in the same way starting from (15S)-16-(3-tributylstannylphenyl)
      17,18,19,20-tetranorisocarba cyclin methyl ester. The decay-corrected
      radiochemical yields were 33-45% based on [11C]methyl iodide produced, and the
      radiochemical purity of the product was > 95%. The total synthesis time was 35
      min, counted from end of radionuclide production to product ready for
      administration. The 11C-labelled prostacyclin methyl esters were easily
      hydrolysed using sodium hydroxide affording the 11C-labelled prostacyclin acids
      in quantitative yields. The stereoisomers (15R)-16-(3-methylphenyl)-17,18,19,20
      tetranorisocarbacyclin [11C]methyl ester and (15S)-16-(3-methylphenyl)
      17,18,19,20-tetranorisocarbacyclin [11C]methyl ester were synthesised by
      esterification using [11C]methyl iodide and the tetrabutylammonium salts of (15R)
      16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin acid and (15S)-16-(3
      methylphenyl)-17,18,19,20-tetranorisocarbacyclin acid, respectively. The decay
      corrected radiochemical yields were in the range of 55% counting from [11C]methyl
      iodide produced, and the radiochemical purity of the product was > 95%. The total
      synthesis time was 35 min, counting from end of radionuclide production to
      product ready for administration. Both of these labelling methods can be used for
      labelling with 13C when (13C)methyl iodide is used. The methods described herein
      have already proved important since they enable the in vivo use of PET to study
      the action of prostacyclins in the brain.

PMID- 9586196
TI  - Henry F. Smyth Jr. Award Lecture. The industrial hygienist as organizational
      culturalist.

PMID- 9586197
TI  - The effects of particle charge on the performance of a filtering facepiece.
AB  - This study quantitatively determined the effect of electrostatic charge on the
      performance of an electret filtering facepiece. Monodisperse challenge corn oil
      aerosols with uniform charges were generated using a modified vibrating orifice
      monodisperse aerosol generator. The aerosol size distributions and concentrations
      upstream and downstream of an electret filter were measured using an aerodynamic
      particle sizer, an Aerosizer, and a scanning mobility particle sizer. The aerosol
      charge was measured by using an aerosol electrometer. The tested electret filter
      had a packing density of about 0.08, fiber size of 3 microns, and thickness of
      0.75 mm. As expected, the primary filtration mechanisms for the micrometer-sized
      particles are interception and impaction, especially at high face velocities,
      while electrostatic attraction and diffusion are the filtration mechanisms for
      submicrometer-sized aerosol particles. The fiber charge density was estimated to
      be 1.35 x 10(-5) coulomb per square meter. After treatment with isopropanol, most
      of fiber charges were removed, causing the 0.3-micron aerosol penetration to
      increase from 36 to 68%. The air resistance of the filter increased slightly
      after immersion in the isopropanol, probably due to the coating of impurities in
      isopropanol. The aerosol penetration decreased with increasing aerosol charge.
      The most penetrating aerosol size became larger as the aerosol charge increased,
      e.g., from 0.32 to 1.3 microns when the aerosol charge increased from 0 to 500
      elementary charges.

PMID- 9586198
TI  - Improved methods for generation, sampling, and recovery of biological aerosols in
      filter challenge tests.
AB  - In preparation for filter efficiency tests and sampler comparison studies,
      methods of biological aerosol generation, sampling, and filter recovery were
      modified from previous studies. Methods described include (1) techniques for
      generating aerosols that reduced nuisance particles to negligible levels and
      increased the cell culturability of Mycobacterium abscessus by 30%, (2) sampling
      techniques that lowered the detectable range of biological particle size from
      0.65 to 0.45 micron and reduced the sampling flow from the chamber from 28.3 to
      1.5 L/min, and (3) development of methods to remove culturable organisms from
      respirator filter media. These methods were developed for filter challenge tests
      with M. abscessus and were applied to two other bacteria. They may also have
      application to a wider variety of organisms and bioaerosol assessments.

PMID- 9586199
TI  - Effects of variation in exposure to airborne acetone and difference in work load
      on acetone concentrations in blood, urine, and exhaled air.
AB  - Using a physiologically based pharmacokinetic (PBPK) model, the effects of
      variation of exposure concentration of acetone on three biological indicators-
      acetone concentrations in blood, urine, and exhaled air--were investigated. The
      effect of the difference in work load was also examined. It was confirmed that
      the model could be used to estimate acetone concentrations during fluctuating
      exposure by comparing simulated acetone concentrations with the corresponding
      values observed in field surveys. By inputting the exposure situations into the
      PBPK model, the variabilities of the biological indicators were simulated. The
      variation of acetone exposure was expressed by seven 1-hour time-weighted
      averages (CEXPs). The arithmetic means of the CEXPS were 200 and 750 ppm. The
      geometric standard deviations (GSDs) were 1.5, 2.0, and 3.0, representing low,
      moderate, and high variations, respectively. Work loads were set at 15 and 50 W.
      Consequently, there were 12 exposure situations. The acetone concentrations in
      venous blood (CB) and exhaled alveolar air (CA) at 1 minute after the end of the
      work shift were selected as biological indicators of exposure because they were
      predicted to decrease rapidly at the end of exposure and become relatively stable
      after 1 minute. The acetone concentration in urine excreted during the last 2
      hours of the work shift (CU) was also used as a biological indicator. Simulation
      was repeated 100 times with randomly permuting CEXPs for each situation. The mean
      values of CB, CU, and CA showed almost no variation regardless of the difference
      in the GSD of CEXPs. The coefficients of variation increased with the GSD of
      CEXPs but were less than 0.2. Consequently, these variables were acceptable as
      biological indicators of daily average exposure for the same work load. However,
      the difference in work load greatly changed the mean values of CB, CU, and CA,
      thus making it difficult to use these variables as indicators of daily average
      exposure for different work loads.

PMID- 9586200
TI  - Assessing airborne aflatoxin B1 during on-farm grain handling activities.
AB  - The presence of aflatoxin in corn and corn dust during relatively normal years
      and the increased risk of Aspergillus flavus infestation during drought
      conditions suggest that airborne agricultural exposures should be of considerable
      concern. Liquid extraction, thin layer chromatography, and high pressure liquid
      chromatography were used for the analysis of aflatoxin B1 in grain dust and bulk
      corn samples. A total of 24 samples of airborne dust were collected from 8 farms
      during harvest, 22 samples from 9 farms during animal feeding, and 14 sets of
      Andersen samples from 11 farms during bin cleaning. A total of 14 samples of
      settled dust and 18 samples of bulk corn were also collected and analyzed. The
      airborne concentration of aflatoxin B1 found in dust collected during harvest and
      grain unloading ranged from 0.04 to 92 ng/m3. Higher levels of aflatoxin B1 were
      found in the airborne dust samples collected from enclosed animal feeding
      buildings (5-421 ng/m3) and during bin cleaning (124-4849 ng/m3). Aflatoxin B1 up
      to 5100 ng/g were detected in settled dust collected from an enclosed animal
      feeding building; however, no apparent correlation was found between the airborne
      concentration of aflatoxin B1 and its concentration in settled dust or bulk corn.
      The data demonstrate that farmers and farm workers may be exposed to potentially
      hazardous concentrations of aflatoxin B1, particularly during bin cleaning and
      animal feeding in enclosed buildings.

PMID- 9586201
TI  - Respirator performance ratings for speech intelligibility.
AB  - A respirator degrades speech intelligibility and thus interferes with the ability
      of the wearer to communicate. The magnitude of this degradation is not well
      studied and can vary as a function of numerous parameters. This study
      investigated the performance degradation of speech intelligibility in low-level
      noise for different speaker-listener distances and message sets (single words or
      predictable sentences) that occurred while wearing a respirator compared with not
      wearing a respirator. Thirteen speaker-listener pairs with normal hearing and
      speech were used. Speaker-listener separation distances were 0.61, 1.22, 1.83,
      2.44, 3.05, and 3.66 m (2, 4, 6, 8, 10, and 12 ft) for the respirator condition
      and 1.22, 2.44, 3.05, 6.1, 9.15, and 12.2 m (4, 8, 10, 20, 30, and 40 ft) for the
      no-respirator condition. The means of the scores were used to determine the
      speech performance rating for both the single-word and sentence comprehension
      tests. The performance rating expresses the percentage of performance that can be
      expected while wearing a respirator compared with not wearing a respirator.
      Scores were interpolated linearly at distances at which no data were obtained. As
      expected, the speech performance rating was higher for the sentence comprehension
      test than for the single-word comprehension test at each distance. At a distance
      of 12.2 m, the speech performance rating for the sentence comprehension was 70%.
      For the single-word comprehension test, the speech performance rating was zero
      for distances greater than 9.1 m.

PMID- 9586202
TI  - A survey of New Jersey industrial hygienists and safety engineers: health and
      safety conditions, practices, and priorities for OSHA reform.
AB  - This study reports the results of an analysis of responses from more than 400 New
      Jersey industrial hygienists and safety engineers to a survey examining a wide
      range of health and safety conditions and practices. Findings are reported on a
      number of variables including the types and seriousness of safety and health
      hazards encountered at the respondents' work sites, perceived improvements in
      health and safety conditions, compliance with right-to-know requirements, the
      effectiveness of resources used in correcting hazards, and the barriers
      encountered in addressing hazardous conditions. The respondents were also asked
      to rank their priorities regarding 14 proposals for Occupational Safety and
      Health Administration (OSHA) reform. Opinion questions were scaled to reflect the
      respondent's sense of the importance of each variable. One finding of particular
      interest is that worker involvement in health and safety committees was perceived
      as an "effective" or "very effective" resource by more than one-half of the
      respondents. Changes in the Occupational Safety and Health Act that would
      strengthen requirements for worker participation were among the respondents' top
      priorities for OSHA reform.

PMID- 9586203
TI  - Employees exposed to lead in Washington state nonconstruction workplaces: a
      starting point for hazard surveillance.
AB  - A survey of selected Washington state employers was carried out to (1) determine
      the number of employees working in lead-using businesses, (2) characterize
      processes and tasks where exposures occur, and (3) determine the number of
      employers familiar with the lead standard, lead health effects, and how exposures
      can be controlled. A total of 1822 nonconstruction employers likely to use lead
      were identified using Washington State Department of Labor and Industries files,
      telephone directories, Washington State Department of Ecology files, air sampling
      results from state workplace inspections, and the state's Adult Blood Lead
      Registry. A total of 89.5% of employers returned the mail questionnaire. Of 789
      employers responding that they engaged in lead-using tasks, 45% stated they were
      aware there was an Occupational Safety and Health Administration standard for
      lead, 21% had done air sampling for lead, 17% had done blood-lead screening, and
      76% reported some type of industrial hygiene measures to control exposures. The
      most commonly reported lead-using activities included soldering; auto repair;
      scrap metal handling; sanding; cutting or welding surfaces coated with leaded
      materials; painting with leaded paints; and radiator repair. A total of 18,970
      nonconstruction workers (and 9416 construction workers) were estimated to be lead
      exposed in Washington in 1995. Identification of potentially exposed workers
      through hazard surveillance and characterization of workplace knowledge and
      practices (through survey and the registry) has allowed the Department of Labor
      and Industries to target resources toward industries most in need of exposure
      reduction efforts.

PMID- 9586204
TI  - Changes in infants' cries as a function of time in a cry bout.
AB  - The present study examines changes in cry sounds over the course of a relatively
      long bout of crying. Specifically, differences in acoustic characteristics of 5
      cries from early and 5 cries from late in a prolonged cry bout were assessed. The
      results indicated that several features changed in means and/or variances between
      early and late in the bout. A subset of 9 acoustic features was chosen to
      evaluate changes in the interrelations of features over time. Cries from late in
      the bout appeared to result from a smaller number of factors, which were more
      readily interpretable in terms of a standard model of cry production. Thus, it
      appears that as infants' level of arousal or distress changes, so do the acoustic
      features of their cries. Further, the results support the notion that bouts of
      crying settle into a "basic" or regular cry whose acoustic features provide a
      reasonable match with a theoretical model of cry production.

PMID- 9586205
TI  - Levels-of-processing effects in infant memory?
AB  - In 3 experiments, we manipulated 3-month-olds' attention to different components
      of a training display and assessed the effect on retention of those components.
      Attention was manipulated via a pop-out display (one target amidst 6 distractors)
      that enhances selective attention to the target relative to the distractors, and
      retention was assessed with displays composed entirely of targets or distractors.
      In Experiment 1, infants recognized both target and distractors after 1 day,
      confirming that both are initially encoded at some level. In Experiment 2,
      infants recognized a target L and distractor Ls after delays longer and shorter,
      respectively, than infants trained with Ls in a homogeneous display. Experiment 3
      replicated the preceding pattern of results with a + stimulus. Thus, increasing
      or decreasing attention to an item during encoding produces a corresponding
      increase or decrease in its memorability. This finding is consistent with a
      levels of processing account and is inconsistent with accounts that deny a
      capacity for explicit memory to prelinguistic infants.

PMID- 9586206
TI  - Words and gestures: infants' interpretations of different forms of symbolic
      reference.
AB  - In 3 experiments, we examine the relation between language acquisition and other
      symbolic abilities in the early stages of language acquisition. We introduce 18-
      and 26-month-olds to object categories (e.g., fruit, vehicles) using a novel word
      or a novel symbolic gesture to name the objects. We compare the influence of
      these two symbolic forms on infants' object categorization. Children at both ages
      interpreted novel words as names for object categories. However, infants'
      interpretations of gestures changed over development. At 18 months, infants
      spontaneously interpreted gestures, like words, as names for object categories;
      at 26 months, infants spontaneously interpreted words but not gestures as names.
      The older infants succeeded in interpreting novel gestures as names only when
      given additional practice with the gestural medium. This clear developmental
      pattern supports the prediction that an initial general ability to learn symbols
      (both words and gestures) develops into a more focused tendency to use words as
      the predominant symbolic form.

PMID- 9586207
TI  - Rapid word learning by fifteen-month-olds under tightly controlled conditions.
AB  - Infants (12 to 17 months) were taught 2 novel words for 2 images of novel
      objects, by pairing isolated auditory labels with to-be-associated images.
      Comprehension was tested using a preferential looking task in which the infant
      was presented with both images together with an isolated auditory label. The
      auditory label usually, but not always, matched one of the images. Infants looked
      preferentially at images that matched the auditory stimulus. The experiment
      controlled within-subjects for both side bias and preference for previously named
      items. Infants showed learning after 12 presentations of the new words. Evidence
      is presented that, in certain circumstances, the duration of longest look at a
      target may be a more robust measure of target preference than overall looking
      time. The experiment provides support for previous demonstrations of rapid word
      learning by pre-vocabulary spurt children, and offers some methodological
      improvements to the preferential looking task.

PMID- 9586208
TI  - Children's understanding of pictorial and mental representations.
AB  - Two studies demonstrate dissociation between children's understanding of
      pictorial representations (photos and drawings) and mental representations
      (beliefs). In Study 1, 37 preschoolers were tested on false belief, appearance
      reality, false photo, and false drawing tasks. The false picture tasks were
      significantly easier, and no correlation was found between children's
      performances on false belief and false picture tasks. In Study 2, 30 children who
      failed a false belief pretest were randomly assigned to 3 training groups: Belief
      (trained on false belief tasks), Picture (trained on false picture tasks), or
      Control (trained on number conservation tasks). Training was conducted in 2
      sessions over the course of 2 weeks; tasks were presented and feedback was
      provided. All children were posttested on theory of mind tasks, false picture
      tasks, and a number conservation task. The posttest results showed differential
      patterns of performance, with the Belief group scoring highest on the theory of
      mind posttests, the Picture group scoring highest on the false picture posttests,
      and the Control group scoring highest on the number conservation posttest.
      Results are discussed with respect to competing models of theory of mind
      development.

PMID- 9586209
TI  - The effects of theories on children's acquisition of family-resemblance
      categories.
AB  - Two experiments examined whether 4- to 5-year-olds' acquisition of family
      resemblance categories (for fictitious animals) was benefited by giving them a
      theory that explained the behaviors of category members ("fighter" versus
      "hider") in terms of the relations between functional surface features. As gauged
      by immediate and 24-hour-delayed categorization tests, children who performed
      theory-guided learning were more successful at making feature/category
      associations than those who performed similarity-guided learning. The Theory
      group categorized individual attributes significantly better than children for
      whom features of the training examples were identified simply by pointing and
      naming (Features condition, Experiment 1) or who were taught unrelated functions
      for features such that they could not be united within any obvious causal schema
      (Features Description condition, Experiment 2). These results support claims that
      mere similarity is insufficient to support category acquisition (Murphy & Medin,
      1985) and show that theories giving an explanation for the existence of
      correlated properties can assist children to learn the distribution of perceptual
      attributes across categories.

PMID- 9586210
TI  - Are lions and tigers substitutes or associates? Evidence against slot filler
      accounts of children's early categorization.
AB  - Items in event-based categorical relations, or "slot fillers," have been found to
      be recalled better by children than items in a taxonomic relation. This has been
      used as evidence that children's memory is organized around script-based
      representations rather than taxonomic structures. Others have attributed the
      superior recall of slot fillers to association and typicality rather than memory
      structure per se. This study was designed to see if the slot filler advantage
      remains when association and typicality were controlled for. Forty-five 3- to 4
      year-olds were tested using a cued recall procedure in which typicality and
      association were varied for slot filler versus taxonomic coordinate lists of
      items. Only children receiving the typical + high association slot filler list
      showed significantly better recall than the taxonomic coordinate list. There were
      no differences between the atypical + low association slot filler list and the
      taxonomic coordinate list. These results suggest that the slot filler advantage
      can be attributed to the more traditional mechanisms of association and
      typicality.

PMID- 9586211
TI  - Together wherever we go: the ethnographic child and the developmentalist.
AB  - Krackow and Gordon aim to refute the slot-filler (SF) model of taxonomic
      knowledge development. On this model, preschoolers derive "slot-filler"
      categories from event schemas. SF categories are items that fill the slots
      created by the actions or functions within an event. They combine into coordinate
      categories, based on general functions, in the school-aged years. This model,
      which has received considerable empirical support across methodologies, ages, and
      sociocultural contexts, relies on the "ethnographic child"--one who has knowledge
      of and participates in a sociocultural world. The SF account is not disproved by
      Krackow and Gordon, which offers no new or alternative category development
      account. Their method and theorizing are a poor fit to children, ethnographic or
      otherwise, undermining the study's capacity to say something reliable and
      representative about cognition in preschoolers. Moreover, if the data are to be
      relied on, they are supportive of the SF model.

PMID- 9586212
TI  - Fear and anger regulation in infancy: effects on the temporal dynamics of
      affective expression.
AB  - Emotion regulation has been conceptualized as the extrinsic and intrinsic
      processes responsible for monitoring, facilitating, and inhibiting heightened
      levels of positive and negative affect. Regulation of distress is related to the
      use of certain behavioral strategies. Our study examined whether putative
      regulatory behaviors widely assumed to be conceptually associated with these
      strategies are actually empirically associated with the changes in fearful and
      angry distress in 6-, 12-, and 18-month-old infants. Our key finding was that the
      use of some putative regulatory behaviors (e.g., distraction and approach)
      reduced the observable intensity of anger but were less effective in reducing the
      intensity of fear. The results suggest (1) caution in assuming that postulated
      regulatory behaviors actually have general distress-reducing effects and (2) the
      likelihood that "distress" is too global a construct for research on emotion
      regulation.

PMID- 9586213
TI  - Individual differences in emotionality in infancy.
AB  - In this multimethod investigation of early emotionality, we observed 112 8- to 10
      month-olds' responses to standard procedures consisting of multiple brief
      episodes that elicited joy, fear, anger, and discomfort to aversive stimulation.
      We obtained parental reports about the infants' temperament and observed their
      emotional tone during naturalistic interactions with their mothers. Parameters of
      emotional response to the standard procedures (latency, discrete behaviors, and
      average and peak intensity across facial, vocal, and bodily channels) cohered
      strongly within each episode. To a lesser extent and with the exception of anger,
      they also cohered across episodes targeting the same emotion. The four emotions
      appeared orthogonal, except for the peak intensity of response, which cohered
      modestly across the 3 negative emotions. The emotionality measures converged to
      some extent: responses to the standard procedures and father-reported temperament
      related meaningfully to the infant's emotional tone in mother-child interactions.
      As predicted, infants' capacity for focused or effortful attention was modestly
      associated with better modulated negative emotionality.

PMID- 9586214
TI  - Children's thinking about traits: implications for judgments of the self and
      others.
AB  - The relation between the way in which children interpret human behavior and their
      beliefs about the stability of human traits is investigated. In interviews with
      202 7- and 8-year-olds across 2 studies, the belief that traits are stable
      predicted a greater tendency to make trait judgments, and an increased focus on
      outcomes and behaviors through which traits can be judged. In the academic
      domain, a belief in trait stability was associated with an emphasis on the
      evaluative meanings of performance outcomes, as opposed to mediating processes
      such as effort. In the sociomoral domain, the same belief was associated with an
      emphasis on the evaluative meanings of behaviors (e.g., whether the person is
      good or bad), as opposed to factors that mediate behavior, such as intention.
      Results suggest that beliefs about the stability of traits may serve an important
      role in thinking about and functioning within the academic and sociomoral
      domains.

PMID- 9586215
TI  - Children's and adolescents' understanding of rights: balancing nurturance and
      self-determination.
AB  - This study examined the development of young people's understanding of nurturance
      and self-determination rights. One hundred and sixty-nine participants from 5 age
      groups (8, 10, 12, 14, and 16 years of age) participated in a semistructured
      interview containing hypothetical vignettes, in which a story character wished to
      exercise a self-determination right or nurturance right that conflicted with the
      wishes or practices of those in authority. Participants were asked to decide if
      they would support the story character's request for rights and to justify their
      decisions. Younger children (8- to 12-year-olds) were significantly less likely
      to identify both nurturance and self-determination rights as salient than were
      older participants (14- to 16-year-olds). The types of reasoning participants
      exhibited for the two types of rights differed at all ages. Reasoning about
      nurturance rights did not show an age-related progression from concrete to
      abstract, whereas reasoning about self-determination rights was more likely to
      exhibit such a progression. Results suggest that previous attempts to explain the
      development of understanding of rights in terms of global stages does not fully
      capture children's and adolescents' reasoning, and, in particular, such a
      framework may not account for the differences in young people's thinking about
      the 2 types of rights.

PMID- 9586216
TI  - Stability and continuity of child-caregiver and child-peer relationships.
AB  - We examined the relationship quality of 55 (27 girls) 9-year-old children with
      their mothers, teachers, and friends as rated by teachers and by the children
      themselves. The goal of this longitudinal study was to examine stability and
      continuity in the quality of children's relationships between infancy and 9 years
      of age. At age 9, children's perception of their relationships with their
      teachers was associated with their current teachers' ratings of their
      relationships with the children. Children's perceptions of their relationships
      with their mothers were consistent with earlier ratings of attachment security.
      Children's perceptions of their relationships with teachers were predicted by the
      quality of their attachment relationships with their first teachers. Children's
      perceptions of their friendship quality was predicted by preschool teacher
      ratings of friendship quality and the quality of their attachment relationships
      with their first teachers.

PMID- 9586217
TI  - Perceptions of emotional support from mother and friend in middle childhood:
      links with social-emotional adaptation and preschool attachment security.
AB  - Children's (N = 58) perceptions of emotional support from mother and best friend
      were assessed at age 8. Perceptions of support from mother were predicted by
      attachment security at age 4, suggesting continuity in the children's internal
      working model of self in relation to mother. Preschool attachment security
      predicted age 8 perceptions of maternal support better than the mother's actual
      behavior at age 8. Identification of the best friend as a member of one's
      emotional support network was not related to security, but was positively related
      to social competence. However, among insecurely attached children, the greater
      the reliance on the best friend for emotional support, the greater the
      externalizing problems. Compensatory effects of best friend support on the social
      emotional adaptation of insecurely attached children were not found.

PMID- 9586218
TI  - Psychosocial adjustment among children conceived via donor insemination by
      lesbian and heterosexual mothers.
AB  - This study examined the relations among family structure (e.g., number of
      parents, parental sexual orientation), family process (e.g., parents'
      relationship satisfaction, interparental conflict), and the psychological
      adjustment of children who had been conceived via donor insemination. The 80
      participating families, all of whom had conceived children using the resources of
      a single sperm bank, included 55 families headed by lesbian and 25 families
      headed by heterosexual parents. Fifty families were headed by couples and 30 by
      single parents. Participating children averaged 7 years of age. Results showed
      that children were developing in normal fashion, and that their adjustment was
      unrelated to structural variables such as parental sexual orientation or the
      number of parents in the household. These results held true for teacher reports
      as well as for parent reports. Variables associated with family interactions and
      processes were, however, significantly related to indices of children's
      adjustment. Parents who were experiencing higher levels of parenting stress,
      higher levels of interparental conflict, and lower levels of love for each other
      had children who exhibited more behavior problems.

PMID- 9586219
TI  - The role of maternal control in the development of sex differences in child self
      evaluative factors.
AB  - The major goal of the present research was to examine the role of parental
      control in the development of sex differences in 2 pivotal self-evaluative
      factors in children: taking responsibility for failure and possessing strong
      standards. Parents were expected to use control with and without autonomy
      granting in specific domains differentially with girls and boys on a daily basis,
      and this was expected to foster sex differences in children's self-evaluative
      factors. Ninety-one mothers of elementary school children completed a daily
      checklist for 10 to 21 days. The checklist assessed mothers' everyday use of
      control and autonomy granting in 5 specific domains (helping, monitoring,
      decision making, praising, and disciplining). Children completed self-report
      measures assessing their tendency to take responsibility for failure and the
      strength of their standards. As anticipated, mothers were more likely to employ
      control without autonomy granting with girls than with boys, but were more likely
      to employ control with autonomy granting with boys than with girls.
      Significantly, this pattern of gender socialization partially mediated the
      tendency of girls to take greater responsibility for failure than boys. Although
      there were no sex differences in the strength of children's standards, the
      pattern of gender socialization was associated with the strength of children's
      standards as well.

PMID- 9586220
TI  - Contextual effects of prekindergarten classrooms for disadvantaged children on
      cognitive development: the case of Chapter 1.
AB  - This study explores the effects of the social context of Chapter 1
      prekindergarten classrooms on children's learning. Chapter 1 (also called Title
      I) is a federal government preschool program directed at children in low-income
      schools who are at risk of later school failure. Using hierarchical linear
      modeling (HLM) and a sample of 677 4-year-olds in 55 1990-91 Chapter 1
      prekindergarten classes in 5 states, the study explores factors that influence
      gains on the Preschool Inventory (PSI) over the preschool year. Social context is
      defined here mainly in terms of the cognitive and social composition of the
      classroom. Contextual factors defined in terms of demographics are shown to be
      related to learning, but the average cognitive level of the class is not. On
      average, children learn less in classrooms with high concentrations of
      minorities, children with special needs, recent immigrants, and children whose
      mothers have little education. The study explores differential effects of racial
      concentration on race differences in learning. Policy implications are discussed.

PMID- 9586221
TI  - The influence of extended-year schooling on growth of achievement and perceived
      competence in early elementary school.
AB  - The influence of additional school days on academic and psychosocial skills was
      examined through comparison of an extended-year program (210 days) with a
      traditional program (180 days). Kindergartners matched on background
      characteristics and magnet school attendance received tests of mathematics,
      reading, general knowledge, vocabulary, and perceived competence at the beginning
      (Fall K) and end (Spring K) of the traditional kindergarten year and at the
      beginning of the next traditional year (Fall 1). Although groups performed
      equivalently at Fall K, extended-year students outperformed traditional students
      at Fall 1 in mathematics, reading, and general knowledge and had higher levels of
      cognitive competence. Mathematics and reading achievement differences at Fall 1
      were not associated with differences in the quality or intensity of educational
      efforts made during the traditional school year (i.e., Fall K to Spring K) or to
      differences between teachers in the traditional and extended-year programs.
      Results indicated that providing students with additional instruction time by
      lengthening the school year could be a promising educational reform.

PMID- 9586222
TI  - Child development and marital relations.
AB  - This article examines aspects of the marital relationship and its assessment
      relevant to scholars of child development. The case for attending to marriage in
      child research is outlined before reviewing what is known about the construct of
      marital quality, behavior, emotional responding, and cognition in marriage.
      Practical recommendations are made for assessing each of these areas before
      arguing that the child's perspective of the marriage is critical for
      understanding children's behavior. Several limitations and promises of marital
      research for understanding children are also discussed.

PMID- 9586223
TI  - Marine natural products.

PMID- 9586225
TI  - The synthesis of O-glucuronides.

PMID- 9586224
TI  - Mycosporines: are they nature's sunscreens?

PMID- 9586226
TI  - Excitatory amino acids.

PMID- 9586227
TI  - Antimicrobial functions of spices: why some like it hot.
AB  - Although spices have been important for centuries in food preparation throughout
      the world, patterns of spice use differ considerably among cultures and
      countries. What factors underlie these differences? Why are spices used at all?
      To investigate these questions, we quantified the frequency of use of 43 spices
      in the meat-based cuisines of the 36 countries for which we could locate
      traditional cookbooks. A total of 4578 recipes from 93 cookbooks was analysed. We
      also complied information on the temperature and precipitation in each country,
      the ranges of spice plants, and the antibacterial properties of each spice. These
      data were used to investigate the hypothesis that spices inhibit or kill food
      spoilage microorganisms. In support of this is the fact that spice plant
      secondary compounds are powerful antimicrobial (i.e., antibacterial and
      antifungal) agents. As mean annual temperatures (an indicator of relative
      spoilage rates of unrefrigerated foods) increased, the proportion of recipes
      containing spices, number of spices per recipe, total number of spices used, and
      use of the most potent antibacterial spices all increased, both within and among
      countries. Likewise, the estimated fraction of bacterial species inhibited per
      recipe in each country was positively correlated with annual temperature. Several
      alternative hypotheses were considered--that spices provide macronutrients,
      disguise the taste and smell of spoiled foods, or increase perspiration and thus
      evaporative cooling; it also is conceivable that spice use provides no benefits.
      However, none of these four alternatives was well supported by our data. The
      proximate reason spices are used obviously is to enhance food palatability. But
      the ultimate reason is most likely that spices help cleanse foods of pathogens
      and thereby contribute to the health, longevity and reproductive success of
      people who find their flavors enjoyable.

PMID- 9586228
TI  - Matrix-assisted laser desorption/ionization for short tandem repeat loci.
AB  - Matrix-assisted laser desorption/ionization was used for the detection of four
      base short tandem repeats (STR) for clinical samples using a time-of-flight mass
      spectrometer. Since STR plays an important role in genetic disease and human
      identification, this work indicates that laser desorption mass spectrometry has
      the potential to achieve rapid DNA typing for both forensic applications and
      genetic disease diagnosis.

PMID- 9586229
TI  - Characterization of polar urinary metabolites by ionspray tandem mass
      spectrometry following dansylation.
AB  - The present report illustrates the application of dansyl chloride coupled with
      ion spray tandem mass spectrometry (IS-MS/MS) in identifying polar urinary
      metabolites. In the course of the metabolism studies of a drug that is currently
      in development, the urine from rats and dogs was collected following oral
      administration of radiolabelled compound. Urinary metabolic profiles of the rat
      and dog indicated the presence of four major peaks and one major peak,
      respectively, in the radiochromatogram. Since all attempts to identify the peaks
      by conventional MS/MS techniques failed, the metabolites were isolated by
      fraction collection and dansylated. Derivatization of the metabolites resulted in
      the formation of more hydrophobic, readily ionizable species which were more
      sensitive in IS-MS/MS analysis than the underivatized metabolites. Examination of
      the molecular ions and the product ion mass spectra of these derivatives revealed
      the structures of all the urinary metabolites. The metabolites in the rat and the
      dog were 4-hydroxyphenylpiperazine glucuronide (M1), 1,4-dihydroxyphenyl
      glucuronide (M2), 1,4-dihydroxyphenyl sulfate (M3) and phenylpiperazine (M4).
      Thus, derivatization with dansyl chloride in conjunction with tandem mass
      spectrometry is a useful tool in identifying polar urinary metabolites.

PMID- 9586230
TI  - High performance liquid chromatography mobile phase composition optimization for
      the quantitative determination of a carboxylic acid compound in human plasma by
      negative ion electrospray high performance liquid chromatography tandem mass
      spectrometry.
AB  - A systematic investigation was undertaken to study the effects of varying
      concentrations of additives in the acetonitrile/water high performance liquid
      chromatography mobile phase, especially formic acid and ammonium formate, on the
      negative ion electrospray response of a carboxylic acid compound. The study
      showed that the response progressively decreased with increase in the formic acid
      concentration. While such a decrease in the response could be qualitatively
      explained by the decrease in the concentration of the ionized form of the
      carboxylic acid compound due to the lower pH of the mobile phase, the change in
      response was not as large as expected from the change of the concentration of the
      ionized form. The response also progressively decreased with increase in the
      ammonium formate concentration but the decrease cannot be explained by the change
      in the pH of the mobile phase. Although the best negative ion electrospray
      response was obtained with a water/acetonitrile mobile phase that contained no
      additives at all, the retention time of the analyte was not found to be
      adequately reproducible on repeated injections. Thus, this mobile phase was
      deemed unacceptable for practical, routine use. Comparing formic acid against
      ammonium formate, the former was preferable since it caused a smaller attenuation
      of the negative ion response. Equally important was the fact that addition of
      formic acid had the desirable effect of maintaining a reasonably high capacity
      factor (k') for the analyte even at a relatively high acetonitrile concentration.
      A concentration of 1 mM formic acid in the mobile phase was large enough to
      achieve the reproducible elongated retention time for the analyte, with a loss in
      the analyte response of about 60% only. It should be noted that the sensitivity
      achieved with the 1 mM formic acid mobile phase, in which the carboxylic acid is
      expected to be about 10% in the ionized form, is about 9 times better than the
      sensitivity achieved in the 1 mM ammonium formate mobile phase, in which the
      carboxylic acid is expected to be about 99% in the ionized form.

PMID- 9586231
TI  - Equilibrium unfolding of proteins monitored by electrospray ionization mass
      spectrometry: distinguishing two-state from multi-state transitions.
AB  - The acetic acid-induced unfolding of cytochrome c (cyt c) and apomyoglobin (aMb)
      are studied under equilibrium conditions by electrospray ionization (ESI) mass
      spectrometry (MS). The folding states of the proteins in solution are monitored
      by the charge state distributions that they produce during ESI. A tightly folded
      protein shows lower charge states than the same protein in an unfolded
      conformation. The ESI-MS data presented in this study show that during the
      denaturation of cyt c, only two distinct charge state distributions are observed.
      These can be attributed to the native and to the acid-unfolded conformation,
      respectively. In the transition region where the folded and the unfolded
      conformation are both present in solution, these two distributions are observed
      simultaneously, thus giving rise to a bimodal ESI mass spectrum. These data
      reflect a highly cooperative (two state) folding behavior. In contrast, the acid
      induced unfolding of aMb is accompanied by gradual shifts in the maxima of the
      observed charge state distribution. This indicates a non-cooperative unfolding
      behavior involving multiple protein conformations. The observations made here
      suggest that ESI-MS might be a general method for assessing the cooperativity of
      protein unfolding transitions. This study also addresses the issue of 'secondary'
      solvent effects for ESI-MS studies on the acid-induced unfolding of proteins.
      These effects influence the ESI charge state distribution without being related
      to conformational changes of the protein in solution and could potentially
      complicate the interpretation of ESI mass spectra. Data obtained for bovine
      pancreatic trypsin inhibitor and ubiquitin indicate that secondary solvent
      effects influence the observed charge state distributions only to a very minor
      extent between pH 8.5 and 2.5.

PMID- 9586232
TI  - Fast-atom bombardment tandem mass spectrometry of cyclic nucleotide analogues
      used as site-selective activators of cyclic nucleotide-dependent protein kinases.
AB  - The mass spectrometric behaviour of six cyclic nucleotide analogues which
      activate cyclic AMP-dependent protein kinase was studied by positive-ion fast
      atom bombardment (FAB) and collision-induced dissociation (CID) mass-analysed ion
      kinetic energy (MIKE) spectrometry. The compounds studied were 1,N6
      ethenoadenosine-3',5'-cyclic monophosphate, (epsilon-cyclic AMP) and 2'-aza-1,N6
      ethenoadenosine-3',5'-cyclic monophosphate, which each activate both isoforms of
      cyclic AMP-dependent protein kinase and have similar affinity for both the 'fast'
      and the 'slow' regulatory site of each isoform, N6-phenyl-cyclic AMP, which is
      selective for the 'fast' regulatory site of each isoform, and 6-chloropurine
      riboside-3',5'-cyclic monophosphate, 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole-3',5'-cyclic monophosphate and 8-(4-chlorophenylthio)
      adenosine-3',5'-cyclic monophosphate, which are each selective for the 'slow'
      regulatory site and preferentially activate isoform II. The FAB- and CID/MIKE
      spectra of the analogues are discussed in relation to their use in studies of the
      regulation of protein kinase activity by quantitative FAB mass spectrometry.

PMID- 9586233
TI  - Investigation of spectral reproducibility in direct analysis of bacteria proteins
      by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass
      spectrometry (TOFMS) can be used for rapid detection of bacteria proteins in a
      crude mixture. It can potentially be used as a tool for bacterial identification
      based on the mass spectral patterns or the appearance of some characteristic mass
      peaks. However, there are many experimental parameters that can potentially have
      a strong effect on the observed mass spectra. The objective of this work is to
      address the mass spectral reproducibility issue. Several experimental parameters
      that may affect the MALDI spectra are systematically investigated. Results of
      spectral comparison from two laboratories with different operators and
      instrumentation are presented. It is demonstrated that minor variations in the
      sample/matrix preparation procedures for MALDI and in the experimental conditions
      used for bacterial protein extraction can result in a significant change in the
      observed spectra, though a number of peaks are conserved in the spectra obtained
      under different experimental conditions from the same bacterial sample. These
      conserved peaks may potentially be used as the biomarkers for bacterial
      identification. It is stressed that this type of investigation on spectral
      reproducibility should be carried out for different bacterial species in order to
      identify the mass spectral peaks that are consistently detected regardless of
      operator and nominal variations in sample preparation approach.

PMID- 9586234
TI  - Analysis of the major mercapturic acid pathway metabolites of benzo[a]pyrene
      found in rat urine by nano-electrospray mass spectrometry.
AB  - Nano-electrospray has been used in combination with high resolution and tandem
      mass spectrometry in the analysis of the major mercapturic acid pathway
      metabolites of benzo[a]pyrene (BP). Accurate mass measurements indicate that the
      [M-H]- ion of the major metabolite has a chemical formula C25H22NO6S, which
      corresponds to the deprotonated form of tetrahydro-trihydroxy-BP-S-N
      acetylcysteine. Tandem mass spectrometry of this [M-H]- ion results in a
      collision induced dissociation spectrum identical to that of synthetic 7,8,9,10
      tetrahydro-8,9,10-trihydroxy-BP-7-S-N-acetylcysteine.

PMID- 9586235
TI  - Reverse-phase capillary high performance liquid chromatography/high performance
      electrospray ionization mass spectrometry: an essential tool for the
      characterization of complex glycoprotein digests.
AB  - The B-domain of recombinant human Factor VIII comprises 909 amino acids and is
      extensively N- and O-glycosylated, in that at least 20 different sites are
      occupied by numerous carbohydrate structures. This domain was incubated with
      trypsin and subjected to liquid chromatography electrospray ionization mass
      spectrometry analysis, using an electrospray orthogonal acceleration time-of
      flight mass spectrometer as the detector for a capillary reversed phase HPLC
      separation of the digest. The inherent high mass resolution afforded by this
      instrument provides both ion charge state determination and high accuracy mass
      measurement that are of significant advantage in defining such highly complex
      mixtures.

PMID- 9586236
TI  - On-line liquid chromatography/electrospray tandem mass spectrometry to
      investigate acrylamide adducts with cysteine residues: implications for
      polyacrylamide gel electrophoresis separations of proteins.
AB  - Adduction between acrylamide and cysteine residues is a post-translational
      modification associated with proteins separated by gel electrophoresis. In the
      present article, three model peptides containing 2-4 cysteine residues were
      reduced with dithiothreitol, incubated with acrylamide monomers and examined by
      on-line liquid chromatography coupled to electrospray tandem mass spectrometry.
      Each of the solutions examined in this work revealed the presence of four
      distinct components: the free peptide, two different peptide-acrylamide 1:1
      adducts involving two cysteine residues at different positions within the same
      sequence, and the peptide-acrylamide 1:2 adducts. The use of liquid
      chromatography allowed the separation of components which differed only by the
      site of complexation of acrylamide, while the application of tandem mass
      spectrometry furnished reliable sequencing information permitting the
      identification of most cysteine residues involved in such complexation.

PMID- 9586237
TI  - Innovative strategies for the oral delivery of drugs and peptides.
AB  - Conventional forms of administration for nonabsorbable drugs and peptides often
      rely on parenteral injection, because the intestinal epithelium represents a
      major barrier to the oral absorption of these therapeutic agents. Recently, a
      number of innovative drug-delivery approaches have been developed, including
      entrapment within small vesicles and passage through the space between adjacent
      intestinal cells. This article reviews some of the most promising techniques
      currently available for oral delivery and their possible practical applications
      for the delivery of vaccines and drugs for the treatment of clinical conditions
      that require frequent, chronic parenteral administration.

PMID- 9586238
TI  - Forensic applications of mitochondrial DNA.
AB  - Human mitochondrial DNA has become a useful tool in forensic investigations. Its
      polymorphic nature and maternal inheritance are characteristics that have,
      combined with its sequence information, enabled investigators to identify missing
      persons, war casualties and individuals involved in mass disasters and criminal
      cases. Various screening procedures have been developed to reduce the need to
      sequence samples that do not match, but DNA-sequence information is still
      necessary to verify a match. Even though several challenges remain before
      mitochondrial-DNA-sequence information can be used unambiguously, comparative
      mitochondrial-DNA-sequence analysis appears to be a reliable and powerful means
      for human identification.

PMID- 9586239
TI  - The development of bioartificial nerve grafts for peripheral-nerve regeneration.
AB  - This article describes recent, significant scientific advances leading to the
      development of the bioartificial nerve graft. Schwann cells, which play an active
      role in the repair and function of peripheral nerves, are used to seed a
      synthetic, often resorbable conduit, which is then used to bridge and repair
      nerve gaps caused by injury or disease. By enhancing the rate and extent of
      regeneration, the bioartificial nerve graft holds great promise for improving
      recovery in the peripheral (and central) nervous system.

PMID- 9586240
TI  - Four-dimensional imaging: the exploration of space and time.
AB  - The process of studying dynamic three-dimensional samples has a long history in
      biological research. Recent advances in hardware and software have made it easier
      to visualise and record interior detail from multiple focal planes of three
      dimensional samples as they change over time (four-dimensional imaging). Once
      captured, it is possible to watch these events repeatedly and to analyse them in
      numerous ways. This article discusses the history of and the hardware necessary
      to perform 4D experiments, the various techniques that make 4D imaging possible,
      and the applications and various options for 4D-image analysis.

PMID- 9586241
TI  - Protein engineering and the development of generic biosensors.
AB  - Biosensors exploit the remarkable specificity of biomolecular recognition to
      provide analytical tools that can measure the presence of a single molecular
      species in a complex mixture. A new strategy is emerging in the development of
      biosensor technologies: molecular-engineering techniques are being used to adapt
      the properties of proteins to simple, generic detector instrumentation, rather
      than adapting instruments to the unique requirements of a natural molecule.

PMID- 9586242
TI  - Translating old drugs into new treatments: ribosomal frameshifting as a target
      for antiviral agents.
AB  - Programmed ribosomal frameshifting is used by many viruses to regulate the
      production of structural and enzymatic proteins. Altering the frameshifting
      efficiencies disrupts the virus life cycle and eliminates or reduces virus
      production. Ribosomal frameshifting therefore provides a unique target on which
      antiviral agents can function. This article describes a series of rapid assay
      strategies that have been developed and used to identify potential antiviral
      agents that target programmed -1 ribosomal frameshifting.

PMID- 9586243
TI  - Can the patient's memory of the timing of pain events replace chart notes?
AB  - The reliability of the patient's memory as to when pain remitted and relapsed was
      studied ten years after knee replacement. Pain was chosen because it is the most
      frequent spontaneous patient complaint, and the remission and relapse points in
      time are clinically important. The standard for the comparison was information
      extracted from the medical records. The patient's information on the time of
      remission of pain could not be trusted. For relapse there was a fair but
      insufficient association (Spearman's correlation coefficient + 0.51).

PMID- 9586244
TI  - Delayed appearance of hip fractures in citizens of Bergen born in the countryside
      compared to cityborn.
AB  - Of a total of 1735 consecutive patients admitted to Engen Hospital in Bergen, 299
      had sustained a hip fracture. A distinction was made according to sex, and
      according to whether the patients were born in the city of Bergen or in the
      surrounding rural areas. At the time of fracture, the countryborn had lived on
      average 51 years in Bergen. A delay in fracture appearance of approximately 3
      years in the countryborn relative to the cityborn was found.

PMID- 9586245
TI  - Which procedure gives best results in reconstructing dislocated hip joints in
      cerebral palsy?
AB  - A retrospective study of the surgical repair of dislocated or subluxed hip joints
      in patients with spastic cerebral palsy was carried out to determine the
      procedure with the lowest recurrence rate. An open reduction and a corrective
      femoral osteotomy were combined with different pelvic osteotomies and different
      interventions on the iliopsoas muscle in most cases. The radiological results in
      58 hip joints of 42 patients were assessed with a follow-up time of 5.9 years on
      average (2.8 to 11.0 years). Although some combined procedures were carried out
      in only an small number of cases, we can still draw some conclusions. The results
      were better, if a pelvic osteotomy and an intervention on the iliopsoas muscle
      were performed. An additional iliopsoas transfer made the hip joints more stable
      over the long term than lengthening. For severely deformed acetabula the
      Pemberton osteotomy was superior to the Chiari osteotomy. The Salter osteotomy
      was a good alternative in cases with mild subluxation. With some combined
      procedures the redislocation rate was as high as 66%, whereas the combination of
      an open reduction, a femoral osteotomy, an iliopsoas transfer and a Pemberton or
      Salter osteotomy gave a redislocation rate of only 11%. A concentric reduction of
      the hip joints was necessary. Primarily noncentered joints did not improve during
      the later course.

PMID- 9586246
TI  - The Furlong hydroxyapatite-coated total hip replacement in patients under age 51.
      A 6-year follow-up study.
AB  - Forty-five Furlong hydroxyapatite-coated total hip replacements were reviewed at
      an average of 71 months (46-89) after surgery. Patient's average age at surgery
      was 46 years (31-50). The average Harris hip score at the time of final review
      was 89, and 38 hips (84%) had no pain (28) or only slight pain (10). Three hips
      were revised, none for aseptic loosening. Two cups were loose. The remainder of
      the cups and all the stems were radiographically stable with positive evidence of
      bone ingrowth and no signs of impending failure. One cup showed definite wear of
      the polyethylene liner. Focal progressive osteolytic lesions occurred in the
      calcar region in 3 stable hips (7%). To date the Furlong hydroxyapatite-coated
      implant has produced encouraging results in this group of young patients,
      although longer follow-up is needed to determine its durability.

PMID- 9586247
TI  - [Simple tibiotalar luxation. Apropos of 16 cases].
AB  - Tibiotalar dislocations without fracture are extremely rare lesions. This series
      included 16 patients, 12 of whom have been examined clinically and
      radiographically. The purpose of this study was to specify the injury mechanism
      of the various anatomical types and to assess the long term outcome. The group
      included eight posteromedial dislocations (50%), four posterior dislocations
      (25%), one anterior dislocation, one high variety, one of the Huguier type, and
      one complex dislocation. The sex ratio was 14 males/2 females with an average age
      of 37 years. In half of the cases, dislocations were open. The average follow-up
      period was 11 years (range, 1 to 26 years). The eight closed dislocations and the
      open case type I according to the Cauchoix classification received non-operative
      treatment by reduction in the emergency room and immobilization in a plaster cast
      for 6 weeks. The seven patients who presented open dislocations Cauchoix type 2
      and type 3 were treated by surgical debridement and ligament repair, followed in
      all cases by a plaster cast boot, and in two cases by temporary transplantar
      pinning. Twelve patients were reexamined clinically according to the Gay and
      Evrard modified score, and were radiographically evaluated with lateral and
      anteroposterior views focused on the tibiotalar joint, on both sides, static and
      dynamic. Anatomical factors resulting in predisposition such as medial malleolus
      shortness or lack of coverage of the talus have been evaluated. No patient
      presented tibiotalar joint instability. A 5 degrees to 10 degrees loss in the
      range of dorsiflexion was frequently observed. Two patients presented joint
      stiffness. In four cases, patients complained about paresthesias in the areas of
      the anterior tibial nerve or intermediary dorsal cutaneous nerve. Four cases of
      degenerative arthritis were radiographically observed, two of which presented an
      overall narrowing of the joint over 50%. Degenerative arthritis had occurred
      within the first four years in these 4 cases. The talus coverage index was
      similar to the standard population. Shortness of the medial malleolus was present
      in only two cases. The long-term prognosis after tibiotalar dislocation without
      fracture proves to be good. One should favor orthopedic treatment. The absence of
      tibiotalar instability argues against carrying out emergency ligamentous repair.
      Evolution towards degenerative arthritis is to be anticipated in 25% of cases,
      especially following open dislocations, or if transplantar pinning was required
      due to instability of the initial reduction.

PMID- 9586248
TI  - [Subungual exostoses. A retrospective study of a series of 28 cases].
AB  - Subungual exostosis represents an uncommon osteocartilaginous benign
      proliferation with a trend towards recurrence. The authors report on a
      retrospective series of 28 cases of subungual exostosis of the first toe with
      histologic confirmation. There were 20 male and 8 female patients, with a mean
      age of 18 years. A history of trauma or repetitive microtrauma was noted in 21
      cases. Surgical treatment was performed using the most direct approach. The tumor
      was widely excised and the ungual apparatus was reconstructed under optic
      magnification. All patients were reviewed after 14 to 96 months. Tumor recurrence
      was observed in 4 cases, treated secondarily with success. No malignant
      transformation was seen.

PMID- 9586249
TI  - [Giant cell tumors of the distal end of the radius treated by resection
      arthrodesis].
AB  - The distal end of the radius is one of the sites commonly affected by giant-cell
      tumor of bone; it poses problems of reconstruction after resection of the distal
      radius. The authors present a retrospective study of 5 giant cells tumors treated
      by resection-arthrodesis of the wrist. These tumors were seen in 3 men and 2
      women. From the radiological point of view, all tumors were extensive and lytic
      lesions centered in the epiphysis and involving the metaphysis; the wrist joint
      was respected. From the histological point of view, the tumors were grade I in 3
      cases and grade II in 2 cases. With a mean follow up of 8 years, the results were
      considered good in 3 cases, fair in 1 case and poor in 1 case. A high incidence
      of bone complications was noted: delayed union (up to 11 months) and fracture of
      the graft, which occurred in 3 patients.

PMID- 9586250
TI  - [Troublesome radiologic changes after reconstructive fixation of the anterior
      cruciate ligament with resorbable interference screws].
AB  - The authors report worrisome radiological changes which were noted after
      implantation of absorbable interference screws in ligamentoplasty at the knee
      joint. Seventeen screws were implanted between September 1995 and July 1996, in
      eleven patients (average age 27) who were operated upon for chronic anterior knee
      instability. They underwent a modified Kenneth Jones procedure using autografts
      with absorbable interference screws (Acufex in 2 cases and Bio-interferix in 9
      cases). Significant enlargement of bone tunnels and bony sclerosis of their edges
      were noted in every patient, but without any modification in the positioning of
      the graft. No clinical instability was observed in any of the patients, with one
      to two years follow-up. Publications on this topic are scarce except for one
      author who reported enlargement of bone tunnels after using bone-patellar tendon
      bone allografts. Resorption of absorbable screws probably induces a marked
      inflammatory reaction, with radiological changes reminiscent of those sometimes
      observed after tendon allografts. Although the radiological changes reported here
      may not affect the graft fixation, the authors have reverted to using metallic
      interference screws.

PMID- 9586251
TI  - Postoperative changes of erythrocyte sedimentation rate, plasma viscosity and C
      reactive protein levels after hip surgery.
AB  - We measured the behavior of the erythrocyte sedimentation rate (ESR), plasma
      viscosity (PV), and C-reactive protein (CRP) in 66 patients who underwent hip
      implant operations, from day 0 to day 21 postoperation. We analyzed the behavior
      of these parameters after the trauma of the operation. We identified a subset of
      patients with evidence of superficial clinical infection/inflammation, where the
      magnitude and duration of the response to surgery was different from the main
      group. PV and CRP show less variability between patients and consequently are
      better indicators of the acute phase response than the ESR which requires a
      series of values in order to demonstrate a trend. PV can be obtained simply and
      rapidly, which would make it a powerful tool in determining persistent
      inflammation.

PMID- 9586252
TI  - Neuroaugmentation in the treatment of complex regional pain syndrome of the upper
      extremity.
AB  - The authors report their results on 36 patients with advanced stages of complex
      regional pain syndrome. They were treated with either spinal cord stimulation, or
      peripheral nerve stimulation, and in some cases with both modalities. Thirty six
      months after implantation the reported pain measured on visual analogue scales
      was an average of 53% better, this change was statistically significant.
      Analgesic consumption decreased by about 50% or was reportedly more effective.
      The authors conclude that in late stages of complex regional pain syndrome,
      neuroaugmentation is a reasonable option when alternative therapies have failed.

PMID- 9586253
TI  - Partial peripheral neuropathy and denervation induced adrenoceptor
      supersensitivity. Functional studies in an experimental model.
AB  - Sciatic nerve ligation in rats (chronic constriction injury (CCI)) induces
      clinical signs and symptoms that mimic human conditions of neuropathic origin,
      such as reflex sympathetic dystrophy (RSD). Denervation-induced supersensitivity
      to (circulating) catecholamines has been implicated in sympathetic dysfunction in
      the CCI model as well as in RSD. In the present paper we studied functional
      properties of sympathetic innervation in subcutaneous resistance arteries,
      isolated from the hind paw of rats 3 weeks after ligation. Contractile responses
      to electric field stimulation of adrenergic nerves and exogenously administered
      cumulative doses of various adrenergic agonists were studied using a myograph. As
      compared to the contralateral side, subcutaneous arteries from the ligated side
      were less responsive to electrical field stimulation. Besides, as compared to the
      contralateral side, subcutaneous arteries from the ligated side showed increased
      sensitivity to alpha 1-adrenoceptor stimulation. This study demonstrates that
      sympathetic dysfunction in an experimental model of neuropathic pain consists of
      denervation-induced supersensitivity to catecholamines rather than of an
      afferently-induced increase in efferent sympathetic nerve impulses.

PMID- 9586254
TI  - Different patterns of extension and recurrence in algodystrophy.
AB  - A true recurrence at exactly the same site is quite unusual in algodystrophy.
      Local or regional extension is possible. The bone scan is an easy way to
      demonstrate that the areas successively affected are not the same. An apparent
      local recurrence could in fact be a microscopic compression fracture of
      trabecular bone or cortical fractures or part of a factitious disorder.

PMID- 9586255
TI  - Further vascular, bone and autonomic investigations in algodystrophy.
AB  - Direct clinical observation is the most common means of diagnosing algodystrophy.
      Further investigations may be helpful to rule out other pathological conditions,
      such as occult or stress fractures or avascular osteonecrosis and to obtain a
      better understanding of algodystrophy. Transient vascular hyperpermeability in
      the affected part is well demonstrated by the clinical findings, the MRI signs,
      and the three-bone scan features. 99m Technectium EHDP bone scan provides an
      evaluation of the vascular abnormalities and of the osteoblastic activity. Dermal
      microcirculation and its reactions to sympathetic stimuli are investigated by
      laser doppler fluximetry and videophotometric capillaroscopy. Perhaps the sweat
      test does unveil what might be specific about algodystrophy. The amount of bone
      loss in algodystrophy in a few weeks or months is what might be expected over 10
      years during the natural history of uncomplicated osteoporosis. An initial
      fracture is undoubtedly an initiating event in the appearance of algodystrophy,
      but patients suffering from algodystrophy may still have significant osteoporosis
      for a long period and hence be at risk for fracture. Densitometry could be an aid
      to the diagnosis and probably to monitoring treatment as well. The local
      colonization of fibroblasts following the transient stage of hyperpermeability
      must be kept in mind to explain the results of joint, bone, muscles or
      neurological investigations in late algodystrophy.

PMID- 9586256
TI  - [Percutaneous treatment of an osteoid osteoma of the scapula using a laser under
      scanner control].
AB  - The authors report a new therapeutic modality used in a patient with an osteoid
      osteoma of the scapula. The young patient complained of pain increasing over the
      last 4 years and not responding to medical therapy. The nidus was successfully
      destroyed by percutaneous laser photocoagulation under CT guidance. Clinical
      improvement was manifest after 72 hours and the patient remained asymptomatic at
      8 months follow-up.

PMID- 9586257
TI  - Ipsilateral omovertebral bones in the levator scapulae muscle and the rhomboid
      muscle in a Sprengel deformity: case report.
AB  - Our interest was stimulated by the uncommon case of a 4-year-old girl who
      presented a Sprengel deformity associated with two omovertebral bones on the same
      side. The first omovertebral bone was situated in the levator scapulae muscle and
      the second omovertebral bone was lying in the rhomboid muscle. The removal of
      these two bones was combined with a Woodward procedure to obtain a good
      correction.

PMID- 9586258
TI  - Unusual evolution of a benign-looking cortical defect of the proximal humerus. A
      case of intracortical osteosarcoma?
AB  - A case of an osteosarcoma following a pathological fracture through a small
      benign-looking cortical lesion of the proximal humerus is described. The unusual
      evolution from a small cortical lesion to a malignant lesion raises the question
      whether this is a case of an intracortical osteosarcoma that has some distinct
      features from those of previously reported cases.

PMID- 9586259
TI  - Median nerve neuropathy from an old lunate dislocation.
AB  - The case of an old volar dislocation of the lunate, associated with median nerve
      neuropathy, is described in a 37-year-old patient. The treatment took into
      account the age of the patient and the relative tolerance to the dislocation. We
      performed a simple excision of the lunate combined with a release of the
      transverse carpal ligament in order to free the median nerve, together with a
      tenosynovectomy of flexor digitorum profoundus. Two years after operation, wrist
      function was virtually complete and the patient was asymptomatic and had resumed
      his occupation.

PMID- 9586260
TI  - Dysplasia epiphysealis hemimelica (Trevor's disease) of the distal radius.
AB  - The authors report a rare case of dysplasia epiphysealis hemimelica (DEH) or
      Trevor's disease of the radius in an Eskimo from Greenland. DEH is
      indistinguishable microscopically from osteochondroma, however its epiphyseal
      site of origin differentiates it from the osteochondroma, which
      characteristically originates in the metaphysis.

PMID- 9586261
TI  - Carpal boss caused by an accessory capitate. Case report.
AB  - A carpal boss is frequently caused by a bony anomaly of the quadrangular joint of
      the carpus. We present the case of a patient with a carpal boss caused by an
      accessory capitate.

PMID- 9586262
TI  - Myositis ossificans in an infant.

PMID- 9586263
TI  - [Microhematuria. Diagnostic norms].

PMID- 9586264
TI  - [Management of female stress urinary incontinence in a specialized unit].
AB  - Urinary exertional incontinence is a very common condition which requires a broad
      range of therapeutic options being available. Besides, the creation of
      specialised units in urology is now evident, one of the areas involved being
      Urogynaecology. To focus the issue of female urinary incontinence, the following
      should be considered: to begin with, treatment is not imperative, patients must
      be evaluated on a case-by-case basis, the least invasive principle must prevail,
      diagnosis must be early, and it should be taken into account that primary and
      secondary prevention is both possible and necessary. A working pattern was
      designed accordingly, to sustain therapeutic decisions, which consisted in a
      detailed anamnesis, complete examination and application of an established
      diagnostic-therapeutic algorithm. Even so, a therapeutic, medical or surgical
      decision will be chosen and patients will be monitored at one, four and sixteen
      months after completion of treatment. To achieve good results in the management
      of female urinary exertional incontinence it is essential to include a large
      number of patients. In fact, the key is to establish a close collaboration with
      the gynaecologists.

PMID- 9586265
TI  - [Analysis of the clinical decision in the initial management of BPH].
AB  - RATIONALE: Diagnostic management of prostate benign hyperplasia remains a
      controversial issue subject to variations as made evident in surveys conducted in
      our country showing that 47.9% urologists regularly perform intravenous
      urography. The aim of this paper was to determine the preferred strategy from the
      standpoint of a more accurate diagnosis for evaluation of patients with prostate
      benign hyperplasia and no absolute indication for surgery. MATERIAL AND METHODS:
      The methodology used was an analysis of the decision taken by elucidation of the
      problem using a decision tree with three major choices: (a) to perform IPSS,
      flowmetry and ultrasound: (b) to perform IPSS and flowmetry, or (c) to perform
      IPSS alone. Basic analysis by estimation of the expected value and three
      sensitivity analysis, one-tailed and two-tailed, were used to see whether the
      dominant choice changed. RESULTS: The choice of performing IPSS alone, resulted
      in accurate diagnosis adjustment in 80.5% cases. When flowmetry was added from
      the beginning, this percentage declined to 66.2%; if ultrasound was also done,
      the decline reached down to 11.2%. The Odds Ratio (OR) for diagnosis imbalance
      was 15.52 and 33, in choice (a) versus choices (b) and (c), respectively. The OR
      for the IPSS and flowmetry choice to cause imbalance versus IPSS alone was 2, 12.
      Also, the choice with greater expected value was IPSS, and this result did not
      change with the sensitivity analysis. CONCLUSIONS: The choice that considers the
      possibility of symptom quantification in the IPSS scale and, based on the
      results, continuation of the diagnostic sequence is the one that should be
      followed, since it provides higher effectiveness from the standpoint of diagnosis
      adjustment.

PMID- 9586266
TI  - [Protocol for coordination with primary care: a new working system in urology.
      Validation].
AB  - BACKGROUND: The Urology Unit at the Costa del Sol Hospital works in coordination
      with the primary health care network using diagnostic and therapeutic protocols.
      OBJECTIVES: To know whether the system is effective based on the analysis of the
      quality of patient referral to Hospital according to the performance of family
      doctors. MATERIAL AND METHOD: The referral document summarising the study
      conducted by the family doctor is analyzed. 578 correspond to conditions already
      coordinated and 269 to other situations not yet covered by the system. RESULTS:
      For the coordinated conditions, 29% referrals are high quality and 45.9% are
      poor. For non-coordinated conditions however, 9.2% are high quality and 57.7%
      poor. The difference is statistically significant (p < 0.001). CONCLUSIONS: Work
      in coordination with primary health care is feasible, effective and probably cost
      efficient.

PMID- 9586267
TI  - [Results of transrectal echography in the study of female urinary stress
      incontinence].
AB  - The development of echographic transducers allows now to study Female Urinary
      Exertional Incontinence (FUEI) using different approaches (vaginal, perineal and
      transrectal). A total of 122 transrectal echographies were performed. Based on
      the clinical symptoms: 14 patients are continent, 15 report micturition urgency,
      11 micturition urgency plus FUEI, and 82 FUEI. All parameters Xrest, Yrest,
      AUVPrest, Xexertion, Yexertion, AUVPexertion, X', Y', AUVP' were measured. Three
      groups were defined: Group I, normal ultrasound diagnosis; Group II, vesical neck
      hypermobility; Group III, FUEI using Kolmogorov-Smirnov's test, the data fits a
      standard distribution curve and the results were analyzed through a variance
      analysis and Newman-Keul's test. During Valsalva's manoeuvre, patients with FUEI
      show greater caudal mobility of the vesical neck which becomes more significant
      as the degree of FUEI increases. Dorsal mobility is also greater in patients with
      FUEI although this parameter is of no use to quantify the degree of FUEI.
      Posterior urethro-vesical angle variability only discriminates patients with no
      FUEI from those with a higher degree of FUEI.

PMID- 9586268
TI  - [Management of hyposalivation caused by oxybutynin chloride in the treatment of
      the unstable bladder].
AB  - OBJECTIVE: To know the incidence of adverse reactions from Oxybutynin Chloride,
      with special reference to salivary hyposecretion and to evaluate the
      effectiveness of the different alternatives employed to solve it. MATERIAL AND
      METHOD: 144 adult patients with signs and symptoms of voiding urgency and
      detrusor-hyperactivity incontinence, who were treated with Oxybutynin 5 to 15
      mg/day. Hyposecretion of several exocrine glands was evaluated using a
      questionnaire that included subjective and objective parameters. For managing
      purposes, patients were divided into 3 groups: 1) General measures; 2) Therapy
      with sialagogues; and 3) Replacement therapy with artificial saliva. RESULTS: 42%
      patients treated with Oxybutynin developed mild-to-moderate hyposialism. 26% had
      severe hyposialism, always related to high dose Oxybutynin. 6% skin dryness, 3%
      eye dryness and 2% dryness in all the above glands (dry syndrome). Regarding
      treatment, most patients with mild-to-moderate hyposialism were managed with
      simple general measures. In severe hyposialism, both sialagogues (Eledoisine) and
      artificial saliva (Bucalsone) were resolutive in over 90% cases. CONCLUSIONS:
      Oxybutynin is an effective drug to stop detrusor hyperactivity, but it has a high
      rate of anticholinergic adverse reactions. There is a number of effective
      therapeutic options available to alleviate these effects, which allow the patient
      to continue with the treatment.

PMID- 9586269
TI  - [Inverted papilloma: presentation of 5 cases and review of the Spanish
      literature].
AB  - Vesical inverted papilloma (IP) is a transitional disease most commonly found in
      the bladder, representing a small percentage within the group of vesical
      neoformations. Although of benign behaviour, some authors advise that a
      relatively strict monitoring should be used considering its high rate of
      proliferative activity. It mainly affects males in their fifth to seventh decade,
      and it presents as any other transitional tumour. In about one fourth of the
      cases a transitional carcinoma becomes associated throughout its evolution, thus
      supporting the theory of periodic monitoring.

PMID- 9586270
TI  - [Percutaneous renal surgery].
AB  - RATIONALE: Analysis of complications resulting from the renal percutaneous
      approach. METHODS: Between 1990 and 1996, 175 percutaneous surgical procedures
      were performed by our group. In 69.2% cases, the reason was a lithiasic
      condition. We also carried out: 35 endopyelotomies, 12 renal cyst resections, 4
      stenosis of uretero-ileal anastomosis, 2 diagnostic nephroscopies and 1 pyelic
      tumour resection. RESULTS: Total rate of complications was 22.2%. Mortality was
      0.5% (one case). Surgery had to be terminated in 13 cases for different reasons.
      Blood transfusions were required in 9 cases. 3 cases of route perforation
      required extended maintenance of nephrostomy. Infectious problems developed in 9
      cases. There were also 2 renocutaneous fistula, one renocolic fistula and one
      pneumothorax. No significant differences were found between the total number of
      complications and the type of treatment carried out. There is however a
      relationship between the lithiasic condition and the haemorrhagic complications
      and also with the failure of the approach. There are no significant differences
      between the number of complications and other variables such as age, sex, side,
      calix approached or duration of surgery. CONCLUSIONS: The percutaneous approach
      to the kidney can be considered as a technique with a low morbidity-mortality
      ratio.

PMID- 9586271
TI  - [Primary epidermoid carcinoma of the renal pelvis].
AB  - Epidermoid carcinomas account for 9 to 17% of primitive pyelocaliceal tumours.
      Key predisposing factor are infections and lithiasis, pre-operative diagnosis
      being difficult due to insidious growth and absence of pathognomonic syndrome.
      The paper introduces one case of epidermoid pyelocaliceal carcinoma where
      diagnosis was supported by intravenous urography, ultrasound and CAT, and where
      the catheter-obtained cytology was definite in terms of diagnostic value.
      Ureteropyeloscopy can be a crucial examination in case of diagnostic doubt.
      Choice therapy is nephroureterectomy with vesical collar resection when the
      tumour's anatomical state or the subtotal nephrectomy allow it. Prognosis of
      these tumours is very poor, mean survival of patients being of about 4 months.
      Our patient died one month after surgery.

PMID- 9586272
TI  - [Vesico-uterine fistula: report of 2 new cases].
AB  - Contribution of two new cases of vesicouterine fistula secondary to a cesarean
      incision. In one case, diagnosis was achieved through cystography and cystoscopy,
      while in the second case cystography, cystoscopy and stain testing (methylene
      blue) were used. In both cases management was through transperitoneal and
      transvesical fistulorrhaphy. The two cases showed favourable post-operative
      evolution with no relapse.

PMID- 9586273
TI  - [Metanephric adenoma. A new embryonal tumor of the kidney].
AB  - Metanephric adenoma is a kidney tumour first identified in 1988 and classified
      within the group of nephroblastic tumours. It is described as a benign tumour
      with no capacity to become malignant or metastatic, predominant in women in a 2:1
      ratio relative to men, and which can develop at any point in life. In most cases,
      it is incidentally found as a result of an abdominal ultrasound study for signs
      and symptoms unrelated to the kidney. Less commonly it presents with pain,
      polycythemia, haematuria or palpable mass. The key radiologic sign is
      calcification, which occurs in a statistically higher proportion than in any
      other renal neoplasia. From the pathoanatomical point of view, the tumour
      consists of small acinus separated by acellular stroma resembling the
      hamartomatous elements of nephroblastomatosis and Wilms' tumour. This paper
      contributes one case of metanephric adenoma, the first one in the national
      literature.

PMID- 9586274
TI  - [Diverticulum of the female urethra: presentation of 3 cases].
AB  - Contribution of three cases of female urethral diverticulum diagnosed and treated
      in our Service. Presence in women presenting to the practice with chronic signs
      and symptoms of the lower urinary tract unresponsive to conventional medical
      management should be ruled out. A review is made of the most significant aspects
      in terms of clinical presentation, diagnosis and therapeutic options.

PMID- 9586275
TI  - [Lumbar ureteral fistula after aortobifemoral bypass in a patient with ileal
      conduit and pelvic irradiation].
AB  - Contribution of a complex case of lumbar ureteral fistula with secondary abscess
      after aortobifemoral bypass in a patient with a background of radical cystectomy
      with ileal conduit and pelvic radiotherapy. A nephrostomy was established and the
      retroperitoneal collection was drained so that in a second phase ureteral
      replacement with ileum could be performed using uretero-ileal terminoterminal and
      ileum-ileal terminolateral by-pass with good therapeutic and functional results.

PMID- 9586276
TI  - [Massive inguinal vesical hernia. Report of 3 cases].
AB  - Vesical hernia is defines as a vesical shift associated to a direct or indirect
      inguinal hernia. It accounts for 0.4-3% of all inguinal hernias, but the
      existence of a massive vesical hernia formation at the inguinoscrotal level is
      uncommon; a total of 114 cases have been found in the literature. Clinically it
      should be suspected every time an inguinoscrotal hernia is found in patients over
      50 years old with urinary flow obstruction. Diagnosis is usually reached through
      serial voiding cystouretrography (SVCU). The preferred treatment should be
      extraperitoneal inguinal herniorrhaphy associated to correction of the
      obstructive process.

PMID- 9586277
TI  - [Ureterohydronephrosis secondary to a cyst of retroperitoneal mesentery].
AB  - Retroperitoneal primary cysts are rare clinical entities. A contribution is made
      of one case presenting this condition with repercussion on the excretory route.
      Ultrasound and computerized axial tomography studies suggest the diagnosis but
      this is confirmed through laparotomy. Choice treatment is enucleation, typically
      easy because of the minimal adherence to surrounding structures. Recurrence is
      rare and malignancy practically non-existent.

PMID- 9586278
TI  - [Retroperitoneal germinal tumor: extragonadal or burned out phenomenon of
      testicular primary? Presentation of a clinical case].
AB  - Clinical record case of a retroperitoneal seminoma with "burned-out" phenomenon
      in the testicular primary, in a 38 year old male with no background of interest
      who consults for a picture of left nephritic colic. The ipsilateral testis study
      detects a fibrotic area with hyalinosis and hemosiderin deposits, although there
      are no tumoral debris, compatible with the "burned-out" phenomenon. Management is
      through surgery plus a chemotherapy protocol. Discussion of the diagnostic
      algorithm of retroperitoneal tumours and the literature on extragonadal germinal
      tumours.

PMID- 9586280
TI  - [Relationship of a benign fibroepithelial polyp and pelvic nephroblastoma].

PMID- 9586279
TI  - [Prepuce simulating an igloo].
AB  - OBJECTIVE: To report what could be the first reference of a prepucial congenital
      abnormality which has been termed an "igloo-like prepuce". The presence of a
      prepuce completely covering the glans and presenting the outer opening on the
      ventral side, resembles the ice constructions used as temporary dwelling by
      certain groups of eskimos. METHODS: Two cases with this unusual abnormality seen
      in two young brothers are described. RESULTS AND CONCLUSIONS: The "igloo-like
      prepuce" is a prepucial congenial abnormality with rare incidence which carries
      no other genitourinary condition but which translates in a merely aesthetic
      alteration.

PMID- 9586281
TI  - The establishment of spermatogenesis in the seminiferous epithelium of the
      pubertal golden hamster (Mesocricetus auratus).
AB  - The present study deals with initial spermatogenesis in the pubertal golden
      hamster (Mesocricetus auratus), in the course of which both the complex process
      of germ cell proliferation and differentiation and the cyclic pattern of
      organization of spermatogenesis are established. Germ cells pass through the
      complete sequence of spermatogenic differentiation from the A-spermatogonium up
      to the mature spermatid between days 12 and 38. During this period, germ cell
      development is already based on the pattern of organization and synchronization
      characteristic of adult spermatogenesis: 1. Judged by the germ cell types
      present, each of the successively appearing germ cell associations conforms to
      one of the adult stages of the seminiferous epithelium (stage conformity of the
      developmental steps of the pubertal seminiferous epithelium). 2. The overall
      intratesticular variance of the developmental levels reached in different tubular
      segments each covers almost exactly one cycle length of spermatogenesis. 3. There
      is a regular, continuous succession of developmental steps along the longitudinal
      course of the tubules which, in every single tubule, comprises the interval of
      one spermatogenic cycle ("wave" of the pubertal seminiferous epithelium). 4.
      Taken together, the latter two results indicate that the tubules of one given
      testis are equal to one another with respect to their developmental level, i.e.,
      they develop synchronously. Germ cell propagation follows the clonal mode of
      proliferation. In quantitative terms, stage-related S-phase indices largely
      parallel the values of adult spermatogenesis. Both the frequently found germ cell
      apoptosis and degenerating intrameiotic spermatocytes correspond to degenerative
      phenomena in the adult seminiferous epithelium with respect to degenerative mode
      and stage-related occurrence. Germ cell development is closely related to the
      maturation of both Sertoli cells and Leydig cells. At two developmental phases,
      localized disturbances of germ cell differentiation occur which are specific to
      the pubertal period and which correlate with a maturational delay of Sertoli
      cells and Leydig cells, respectively: 1. Completion of Sertoli cell barrier
      formation may temporarily follow the initial onset of meiosis in the neighboring
      germ cells. As a result, mitotically dividing germ cells fall under the influence
      of a (hitherto hypothetic) "meiotic milieu" and characteristically degenerate
      (arrested germ cell mitoses). This relationship emphasizes the functional
      significance of the separation of the two seminiferous compartments and, in
      addition, heightens the understanding of the necessity of normal termination of
      Sertoli cell proliferation before germ cells initially enter meiosis. 2. The
      Leydig cell enzyme 11 beta-HSD, which is known to promote testosterone output, is
      established several days after the leading spermatids initially reach step 6 of
      spermiogenesis (which is immediately prior to the particularly testosterone
      dependent start of elongation). The resulting selective developmental arrest of
      round spermatids of steps 6-6/7 between days 26 and 30 leads to a localized,
      partial desynchronization of the seminiferous epithelium, which can be traced for
      several days after the above-mentioned maturational delay of Leydig cells has
      been overcome and which is accompanied by an extensive degenerative disposition
      of the spermatids involved. The present investigation documents an organizational
      and synchronizational level of initial spermatogenesis that is similar to the
      situation in the adult animal. The analysis of temporarily occurring
      perturbations in the process of establishing the pubertal seminiferous epithelium
      emphasizes and specifies the close structural and functional relationships
      between the maturational state of somatic cells and germ cell differentiation.

PMID- 9586282
TI  - The catecholaminergic innervation of the rat amygdala.
AB  - The present study is the first to demonstrate conclusively and to analyze
      systematically synaptic contacts of all three types of catecholaminergic afferent
      fibers in different nuclei of the rat amygdala and to relate the
      catecholaminergic innervation to neurochemically identified target neurons. 4.1.1
      Central Nucleus: The central nucleus is the amygdaloid nucleus receiving the most
      dense catecholaminergic innervation. In the medial central nucleus, dopaminergic,
      noradrenergic and adrenergic terminal plexus overlap, in the central lateral
      central nucleus mainly dopaminergic plexus are found. The lateral capsular
      central nucleus is generally scarcely innervated, but individual neurons of this
      subnucleus possess a dense dopaminergic innervation. Colocalization of
      neurotensin in dopaminergic afferents is rare, the majority of the dense
      neurotensin-ir terminal plexus consist of non-dopaminergic fibers. The
      catecholaminergic innervation of the medial central nucleus is directed
      preferentially at peripheral neuronal structures, and has thus presumably
      modulatory functions. Dopaminergic terminals form predominantly symmetric,
      noradrenergic and adrenergic terminals from preferentially asymmetric synapses. A
      characteristic feature of the dopaminergic innervation is the dense perisomatic
      innervation of selected neurons. Adrenergic and the majority of noradrenergic
      afferent fibers to the medial central nucleus originate from cell groups in the
      medulla oblongata and contain high levels of NPY. GAD mRNA-detection suggests
      that most target neurons of catecholaminergic afferent fibers are capable of
      synthesizing GABA in the medial central nucleus. In its dorsal part, GABA is
      possibly colocalized with somatostatin, and many neurons express the dopamine-1
      receptor subtype mRNA. In the posteroventral medial central nucleus, on the other
      hand, enkephalin mRNA-r and dopamine-2-receptor subtype mRNA-reactive neurons
      show a similar distribution as the GAD mRNA-reactive ones. Contacts could be
      shown between dopaminergic, noradrenergic and adrenergic axons and NPY- and
      somatostatin-immunoreactive neurons which are supposedly among the brainstem
      projection neurons of the medial central nucleus. The dopaminergic innervation of
      the central lateral central nucleus resembles that of the neighboring striatum in
      many respects. The synaptic density is high. As in the medial subnucleus, distal
      neuronal elements are the preferential target structures, indicating a modulatory
      function possibly regulating the selectivity of the target neurons for stimuli
      transmitted by other afferent fibers. Besides, individual neurons possess a dense
      perisomatic, presumably non-selective dopaminergic innervation. The innervation
      does not appear to be targeted at one specific neurochemical type of neuron in
      the central lateral central nucleus, but rather contacts somatostatin- and
      neurotensin-immunoreactive neurons (which are possibly also GABAergic), in
      addition to GABA/enkephalin-synthesizing and other (e.g., CHAT-immunoreactive)
      neurons. Individual neurons of the central lateral central nucleus express the
      dopamine-2-receptor subtype mRNA. The dopaminergic fiber baskets of the lateral
      capsular central nucleus are found surrounding enkephalin mRNA-reactive neurons.
      Codistribution studies suggest that they express the dopamine-2-receptor subtype
      mRNA. 4.1.2 Basal Complex: The basal complex receives dopaminergic and
      noradrenergic innervation, the latter mainly originating in the locus coeruleus.
      Some of the dopaminergic afferents contain neurotensin, and in contrast to the
      central nucleus, all neurotensin-immunoreactive afferent fibers are dopaminergic.
      In the noradrenergic afferent fibers NPY is not detectable. These results and the
      innervation pattern displaying mostly peripheral neuronal target structures
      resemble dopaminergic and noradrenergic innervation patterns documented in
      cortical areas. (ABSTRACT TRUNCATED)

PMID- 9586283
TI  - [Current view and perspectives on the future of pediatric intensive medicine].

PMID- 9586284
TI  - [Special infant formulas].
AB  - INTRODUCTION: Breast feeding is the optimal mode of feeding for the normal
      fullterm infant. Formulas prepared to substitute total or partially human milk
      were available by the end of the last century. The composition of infant formulas
      has evolved greatly, because of the advance of scientific researches, and a large
      array of formulas for particular circumstances is actually available. OBJECTIVES:
      The aim of this article is to revise, compare and discuss the special
      manufactured formulas commercially available. MATERIAL AND METHODS: Record of the
      data from the manufacturer's advise leaflet or formulary for each product, and
      the information provided by each manufacturer after being contacted with them.
      RESULTS: Today there is an ample offer of specific formulas in the market. We
      present the composition of each specific formulas grouped as: Formulas for
      premature, modified formulas in its basic constituents and formulas with addition
      of thickeners. The general characteristics of each group are described, as well
      as indications and possible risks of their use. CONCLUSIONS: Knowledge of the
      characteristics of specific formulas is crucial for a correct prescription and
      choice of the most suitable one for each individual case.

PMID- 9586285
TI  - [Multicenter prospective study on severe bacterial meningitis in children].
AB  - We prospectively studied the epidemiologic, clinic signs and outcome of bacterial
      meningitis in 125 children who were admitted into a PICU (Pediatric Intensive
      Care Unit) of 11 hospitals of Spain and whose meningitis was diagnosed between
      May 1994 and April 1995. RESULTS: The median age of the children was 3.55 +/-
      3.32 years (range 1 month to 16.5 yrs). Eighty-eight were bacterial meningitis,
      probably bacterial 30 and aseptic 7. The most frequently isolated organisms were
      N. meningitidis (52), H. influenza type b (17) and S. pneumoniae (8). Twenty-five
      percent of N. meningitidis had C serotype. Incidence rate of each germen was
      depending of age. All patients diagnosed of H. influenza type b meningitis were
      less than 3 years old. H. influenza type b and meningococcus had similar
      incidence rate during the first year of life (27% versus 31%). During the first
      three years of life H. influenza type b produced one third of bacterial
      meningitis. A mortality rate of 5.6% (seven patients: 3 S. pneumoniae, 1 N.
      meningitidis, 1 H. influenza type b and 2 unknown germen) was observed. Patients
      who die had lower Glasgow coma score (p = 0.034) and seizures (p = 0.001) at
      admission. At discharge of PICU, 9 survivors (7.2%) had sequelae: mental
      retardation in 7 patients and hearing loss in two. One third of patients needed
      hemodynamic support and a 15% of them ventilatory support. CONCLUSIONS: Age is an
      important epidemiological factor in the etiology of pediatric acute meningitis.
      H. influenza type b and N. meningitidis had similar incidence rate during the
      first year of life. S. pneumoniae had the highest mortality rate (37.5%). The
      presence of coma and seizures at admission were associated with mortality.

PMID- 9586286
TI  - [Acute otitis media in the first year of life and its relationship with various
      risk factors].
AB  - OBJECTIVE: The purpose of the present study was to evaluate the frequency of
      acute otitis media (OMA) in our city (urban population) during the first year of
      life and its relationship to some risk factors. PATIENTS AND METHODS: This is a
      retrospective study of 240 children. We collected information about risk factors
      (sex, gestational age, birthweight, duration of breastfeeding, older siblings,
      parental smoking and nursery care). We related these to the number of OMA
      episodes during the first year of life. RESULTS: Of the infants studied 40% had
      suffered at least one episode of OMA during the first year of life. There was a
      higher incidence during winter and spring. Three out of every four episodes
      occurred after six months of age. The incidence of OMA was strongly associated to
      whether there were older siblings (odds ratio: 1.98) and to the male sex (odds
      ratio: 1.98). Children in the breastfed group (exclusive breastfeeding for at
      least 5 months) have less otitis episodes than the milk-adapted formula group,
      but the difference was not statistically different (0.41 +/- 0.68 vs 0.69 +/-
      1.01 episodes; p = 0.11). CONCLUSIONS: In our report, the only risk factor
      strongly related with OMA in suckling infants are the presence of older siblings
      and the male sex. Breastfeeding did not have a protective effect in comparison to
      commercial formula, although a prospective study might be of interest for further
      addressing this issue.

PMID- 9586287
TI  - [Molecular analysis of tumor suppressor genes p16INK4 and TP53 of osteosarcomas
      in Spanish children].
AB  - OBJECTIVE: Alterations affecting tumor suppressor genes, specifically p16INK4 and
      TP53, have been shown to be involved in the development of human cancer due to
      their important role in the control of normal cell cycle progression. As the
      genetic events leading to the development of pediatric osteosarcoma remain
      partially unclear, we have tested the possibility that a significant number of
      pediatric osteosarcoma patients harbor mutations in these genes. PATIENTS AND
      METHODS: We have analyzed 64 samples (fresh tissues, paraffin embedded biopsies
      and peripheral blood lymphocytes) corresponding to 38 pediatric osteosarcoma
      patients. TP53 mutations were analyzed by DGGE (Denaturing Gradient Gel
      Electrophoresis) analysis of exons 5 through 8. We searched for deletions in the
      p16INK4 gene by PCR (Polymerase Chain Reaction) analysis and point mutations were
      screened by means of SSCP (Single Strand Conformation Polymorphisms). RESULTS:
      Our analysis showed that 18.4% of the samples harbored mutations in the coding
      region of TP53 and that 7% had a homozygous deletion of the p16INK4 gene. Our
      results suggest that p16INK4 deletions may constitute a bad prognostic factor and
      that TP53 alterations may be correlated, although not statistically, with reduced
      survival time. CONCLUSIONS: Mutations of the TP53 and deletion of p16INK4 tumor
      suppressor genes seem to be involved in the development of pediatric
      osteosarcoma. Moreover, alterations of these genes may constitute a prognostic
      factor related with poor prognosis or decreased survival time.

PMID- 9586288
TI  - [Familial aggregation in 91 families of hypercholesterolemic children].
AB  - OBJECTIVE: The aim of this study was to evaluate both the importance of the
      screening strategy and the familial aggregation characteristics of families with
      hypercholesterolemic children. PATIENTS AND METHODS: Ninety-one families (369
      subjects) with one hypercholesterolemic child were studied. In addition to
      clinical and general biochemical evaluation, lipids including apo A-I and B-100
      were examined. LDL was quantified under ultracentrifugation. RESULTS: Among the
      91 children studied, 10 (10.99%) suffered heterozygous hypercholesterolemia,
      while 81 (89.01%) suffered polygenic hypercholesterolemia. Following a diet,
      polygenic children exhibited normal lipid parameters. In heterozygous children a
      decrease of 19% for total cholesterol, 19.9% for LDL-cholesterol and 16.3% for
      apo B were observed. When starting the study, 77.5% of the family members thought
      that they had normal serum lipid values. At the end of the study it was confirmed
      that only 28% were really normolipemic, indicating that 49.4% of the individual
      did not know that they were suffering dyslipemia. The study also showed that
      fathers exhibited the highest incidence of hypercholesterolemia (80.2%) followed
      by brothers (65.6%) and mothers (61.5%). Therefore, 69.4% of the individuals
      studied exhibited dyslipemia. CONCLUSIONS: The screening strategy allows one to
      diagnose a high percentage (almost 50%) of individuals suffering
      hypercholesterolemia in families with a child previously diagnosed of this
      pathology. Moreover, in these families there is a high degree of familiar
      aggregation of dyslipemia.

PMID- 9586289
TI  - [Epidural hematoma in children. Prognostic factors. Analysis of 70 cases].
AB  - OBJECTIVE: The aim of this study was to analyze the causes of epidural hematoma
      in order to know its incidence in craneoencephalic trauma and establish
      prognostic criteria. PATIENTS AND METHODS: A retrospective study of 70 children
      with the diagnosis of epidural hematoma between 1990 and 1995 were studied.
      Clinical, radiological, chronologic variables and evolution were analyzed.
      RESULTS: The diagnosis was made during the first 4 years in 63% of the cases.
      Neurologic impairment was present at admission in only 33% of the patients. Ages
      ranged between 7 days and 17 years (mean age: 8 years). Of these patients, 82%
      were admitted to the PICU, 53% were ventilated and 19% needed ICP monitorization.
      Radiological findings on the first CT were skull fracture (68%) and
      temporoparietal epidural hematoma (66%), right-sided (63%). Other kinds of
      lesions were also recorded in the first and subsequent CTs. Three patients died,
      63% recovered fully, 10% had serious sequelae and 23% had some degree of
      neurodisability. CONCLUSIONS: The following data correlated with death or
      neurological impairment: Multiple cerebral contusion (p = 0.002), brain edema (p
      = 0.05), GCS less than 8 on admission (p = 0.002), and shock (p = 0.003). On the
      other hand, neither surgical drainage volume, age, location of the hematoma, nor
      ICP values correlated with a poor prognosis.

PMID- 9586290
TI  - [Usefulness of etiologic studies in children hospitalized for pneumonia].
AB  - OBJECTIVE: The aims of this study were: 1) To assess the effectiveness of viral
      culture and serology. 2) To check if there are clinical differences between
      patients with viral or bacterial infections. 3) Assessment of treatment, previous
      to and during the hospital stay. PATIENTS AND METHODS: A prospective study was
      carried out between January 1994 and June 1995 on 56 inpatients diagnosed of
      pneumonia. The mean age was 3 years (range: 2 months- 14 years). Viral cultures
      on cell monolayers was carried out in 46 patients. Serology was carried out in 33
      patients older than six months of age. Blood cultures were obtained in 27
      patients and a tuberculine reaction was studied in 15 patients. On the basis of
      microbiological results, three groups were formed (viral, bacterial and unknown)
      and clinical symptoms, thorax X-rays, and laboratory data were compared. RESULTS:
      The etiologic agent was detected in 36 patients (64%). The most frequent
      pathogens detected were adenovirus and respiratory syncytial virus with 11
      patients (19%) each, followed by Mycoplasma pneumoniae with 9 patients (16%):
      Viral cultures were positive in 16 patients (35%) and serology in 22 patients
      (66%). Viral infection was detected in 20 patients (36%) and bacterial infection
      in 16 (28%). Mixed infection (bacterial/viral) was found in 5 patients (9%). The
      patients with viral infections showed significant differences (p < 0.01) for age
      (younger) and tachypnea compared with those with bacterial infections. Sixty-six
      percent of the patients had received antibiotic treatment previous to hospital
      admission and 87% during their hospitalization. CONCLUSIONS: Although the
      etiologic studies were positive in 64% of the patients, the delay in obtaining
      the results make them scarcely useful in determining whether to initiate or not
      antibiotic therapy (87% of inpatients). Clinical data, radiology results and
      leukocyte counts do not show any difference between viral and bacterial
      infections.

PMID- 9586291
TI  - [Value of salivary antibodies for determining seropositivity to measles, rubella,
      and mumps in children and adults].
AB  - BACKGROUND: IgA and IgG antibodies can be detected in saliva in order to assess
      the immune status against measles, rubella and mumps. PATIENTS AND METHODS: Serum
      and saliva were simultaneously obtained from 50 adults between 19 and 52 years of
      age that were non-vaccinated and from 50 children from 15 months to 13 years of
      age that had been vaccinated against measles, rubella and mumps at 15 months of
      age. Specific IgG and IgA antibodies were determined by ELISA. Values higher than
      the 95% confidence interval obtained in 39 non-vaccinated and non-infected
      infants were considered as positive. RESULTS: In adults 96-100% and in children
      90-98% were seropositive for the viral antigens studied. A positive result in
      saliva was always higher than 50%, with the percentage being higher in children
      than in adults and mainly for IgA antibodies. According to the present study, the
      combined determination of IgG and IgA antibodies in saliva would detect 86% of
      the children seropositive for measles, 87% for rubella and 82% to mumps, with
      these results being slightly lower in adults. Children without salivary
      antibodies were frequently younger than 3 years of age and were negative for more
      than one viral antigen. CONCLUSIONS: The study of salivary antibodies is a non
      invasive method to assess seropositivity against measles, rubella and mumps, but
      it is advisable that both IgG and IgA antibodies be determined.

PMID- 9586292
TI  - [Is neonatology already a superspecialty?].

PMID- 9586293
TI  - [Prenatal diagnosis and fetal surgery].

PMID- 9586294
TI  - [Postnatal growth in very low birth weight infants: assessment with a new
      somatometric index].
AB  - OBJECTIVE: We have studied the postnatal growth of very low birth weight infants
      by using a differential index in reference to intrauterine growth evaluated by
      means of Lubchenko and Usher graphs. PATIENTS AND METHODS: We analyzed the
      postnatal growth between birth and hospital discharge of 194 infants with birth
      weights less than 1500 g. No selection was made according to pathology and those
      newborns who died are treated as missing values. The differential index was
      calculated as the percentage deviation of the studied parameter and its 10th
      percentile and the range between the 10th and 90th percentiles. RESULTS: The
      weight differential index decreased between birth and hospital discharge (20.8 +/
      33.3 versus -10.03 +/- 30.6, t = 16.97, p < 0.001), as well as that of the
      height differential index (30.9 +/- 39.1 versus -10.05 +/- 44.35, t = 5.65, p <
      0.001), with that of cephalic growth being unchanged (23.2 +/- 43.2 versus 40.4
      +/- 35.4, t = -2.29, p = NS). Newborns included in the early discharge program
      had a worse differential index at the final discharge than at early discharge (
      19.1 +/- 27.9 versus -9.8 +/- 22.2, t = -6.1, p < 0.001). Height and cephalic
      growth was better at the final hospital discharge (-6.6 +/- 46.1 versus 22.7 +/-
      26.1, t = -2.8, p < 0.05; 28.8 +/- 37.7 versus 50.1 +/- 27.5, t = -3.48, p <
      0.01).

PMID- 9586295
TI  - [Is neonatal toxic erythema a risk factor in the development of allergy in
      childhood?].
AB  - OBJECTIVE: In relatively few cases have perinatal factors been included as risk
      factors for allergy development. Delivery has not been considered as a possible
      influential factor in allergy development. To identify risk factors in allergy
      development, we have included erythema toxicum neonatorum (ETN). PATIENTS AND
      METHODS: We have prospectively studied 356 newborns that were followed for a
      period of two years. Characteristics of the delivery, such as the pregnancy,
      instrumental delivery, circular cord, ETN, number of vesicles, day of
      presentation, season of birth, maternal and cord blood IgE levels and cord blood
      eosinophils and the development allergies during the two year follow-up period
      were included. RESULTS: ETN was seen in 25.3% of the children. The histopathology
      study of vesicles showed eosinophils. There was a significant difference between
      males and females (61.9% versus 38.1%, respectively). Cord blood IgE levels were
      not related to ETN, except in situations of allergy from 0.9 IU in cord blood or
      from 20 IU at six months of age (p < 0.05). CONCLUSIONS: ETN is related to
      delivery characteristics, instrumental, circulars, amniotic alteration or fall in
      arterial pH < 7.24. In 84.2% of allergy manifestations during the first two years
      of life, ETN or a low pH was seen at birth, with atopic dermatitis being those
      that displayed ETN (85.7%).

PMID- 9586297
TI  - [Hepatic lesions following parenteral nutrition in premature newborns].

PMID- 9586296
TI  - [Fetal growth retardation: epidemiology and intrauterine growth rate].
AB  - OBJECTIVE: This study aimed at two purposes: 1) To become aware, in our
      environment, of some epidemiological factors of fetal growth retardation in its
      harmonious, non-harmonious and semiharmonious variants. 2) To obtain fetal growth
      curves, from the 31st to the 43rd weeks of pregnancy, of the three types of
      deficiencies and compare them with the intrauterine growth of normal newborns.
      PATIENTS AND METHODS: We have studied the last 249 growth retarded fetuses
      admitted to the Neonatology Service. The statistical study was carried out in
      comparison to 7,720 cases of fetuses with normal growth. RESULTS: The main
      results were the following: 1) An unquestionable influence of a deficient
      educational, laboral and economical level of the mother in the genesis of fetal
      growth retardation. 2) Fetuses with harmonious retardation reached the highest
      gestational ages. 3) The obstetric procedure is conditioned by the fetal growth
      retardation. 4) There was higher morbility in the studied group. 5) The increased
      weekly anthropometry tendency was similar in the three groups of growth retarded
      fetuses.

PMID- 9586298
TI  - [Cavitary tuberculosis in childhood].

PMID- 9586299
TI  - [Prenatal ultrasonography and therapeutic approach in choledochal cyst].

PMID- 9586300
TI  - [Steinert's congenital myotonic dystrophy. Genetic aspects].

PMID- 9586301
TI  - [Bone marrow allogenic transplantation in malignant osteopetrosis].

PMID- 9586302
TI  - [What is your diagnosis? Girl with pelvic mass and fever].

PMID- 9586303
TI  - [Simultaneous high frequency oscillation ventilation and peritoneal dialysis in a
      preterm newborn].

PMID- 9586304
TI  - [Empirical treatment with cephotaxim in Echovirus type 3 meningitis].

PMID- 9586305
TI  - [Reduction of exposure to multiple donors in premature newborns weighing less
      than 1,500 g at birth].

PMID- 9586306
TI  - [Fluoride content in toothpastes: update in 1997].

PMID- 9586307
TI  - [The urologist in renal transplant].

PMID- 9586308
TI  - [Proteins and urinary lithogenesis. Historical revision].

PMID- 9586309
TI  - [Tumor bladder antigen (TBA). A new method for the diagnosis and detection of
      recurrence of bladder cancer].
AB  - OBJECTIVE: To compare the usefulness and accuracy of the BTA test versus urinary
      cytology. METHODS: The BTA test was performed in 45 patients distributed into
      three groups: group I comprised patients with hematuria of unknown origin; group
      II had a diagnosis of bladder cancer; and group III comprised patients who had
      undergone TUR for a bladder tumor and were undergoing endoscopic control
      evaluation. The sensitivity and specificity of each diagnostic method were
      determined for each group of patients. RESULTS: The BTA test showed a higher
      sensitivity than urinary cytology in all groups, the difference being significant
      for groups II and III. Its specificity, however, was lower than that of cytology
      in groups I and III, and similar in group II. CONCLUSION: The BTA test is a
      simple and useful method for the diagnosis and follow-up of bladder cancer. It
      has a higher sensitivity than urinary cytology, although its specificity is lower
      due to the higher number of false positives observed in patients with
      inflammatory bladder conditions. Randomized studies are warranted to determine if
      the accuracy of urinary cytology can be enhanced with the combined use of the BTA
      test which has been demonstrated to have a higher specificity.

PMID- 9586310
TI  - [Nephrogenic adenoma: study of 9 cases, including one of the urethra in a 14-year
      old male].
AB  - OBJECTIVES: To review our series of nephrogenic adenoma and compare our results
      with those reported in the literature. METHOD: The records of our Department of
      Pathology were reviewed to determine the cases of nephrogenic adenoma diagnosed
      at our center. The clinical features, diagnostic aspects, pathological findings,
      treatment and outcome are presented. RESULTS/CONCLUSIONS: Nephrogenic adenoma is
      a rare lesion, probably arising from nephrogenic metaplasia caused by injury to
      the urothelial mucosa. The site of presentation is frequently the bladder,
      followed by the urethra. The diagnosis is based on the histopathological
      findings, which can be occasionally equivocal. The cases described in the present
      series were benign. To date there is no established therapeutic approach. We
      performed TUR in two patients, antibiotic therapy was administered in one patient
      and 4 patients were managed conservatively. Two of our patients had no control
      evaluation following biopsy of the lesion. In 2 of the 4 patients that were
      managed conservatively, the lesion remitted spontaneously.

PMID- 9586311
TI  - [Asymptomatic bacteriuria or "detected" bacteriuria in the female. Incidence in
      our health area].
AB  - OBJECTIVES: To determine the incidence of asymptomatic bacteriuria in women
      consulting at our hospital and its relationship with other chronic diseases.
      METHODS: A cross-sectional study was conducted on 735 women who had consulted at
      our hospital from February to September, 1996. Urinary sediment, serial urine
      culture, serum urea and creatinine values were analyzed. Patient records were
      reviewed to obtain pertinent data for the study. RESULTS: The incidence of
      asymptomatic bacteriuria was 8%; 47.4% of the cases were women over 60 years of
      age. E. coli was identified as the causative organism in 77.9% of the urine
      cultures. Diabetes mellitus was the most frequent associated chronic disease
      (27.1%). The incidence of renal damage was not statistically significant and was
      not directly related with bacteriuria. CONCLUSIONS: We emphasize the importance
      of performing a urine culture when leukocyturia is detected. The incidence of
      asymptomatic bacteriuria increases with age. E. coli was the most frequent
      causative organism. Diabetes mellitus was the most frequent associated chronic
      disease. The incidence of renal damage was not statistically significant.

PMID- 9586313
TI  - [Sarcomatoid renal carcinoma].
AB  - OBJECTIVE: To analyze the pathological and clinical features of a variant of
      renal carcinoma: sarcomatoid renal carcinoma. METHODS: Of 316 patients diagnosed
      as having a renal tumor from 1975 to 1995, 11 (3.5%) with a pathological
      diagnosis of sarcomatoid renal carcinoma were analyzed. The clinical history,
      biological data and diagnostic imaging findings of these patients were reviewed.
      All patients had undergone surgical exploration. RESULTS: All the tumors showed a
      double cellular population, with a fusiform component. Histological analysis
      showed a high grade and stage tumor. Ten patients died from the disease, the mean
      survival rate was 9 months (range 2-48) following diagnosis. CONCLUSIONS:
      Sarcomatoid carcinoma of the kidney is uncommon and can be occasionally difficult
      to distinguish from sarcoma. It has a worse prognosis than other variants of
      renal carcinoma.

PMID- 9586312
TI  - [Evaluation of megestrol acetate as monotherapy in disseminated prostatic
      carcinoma].
AB  - OBJECTIVE: To determine the effects of megestrol acetate on testosterone,
      dehydroepiandrosterone and PSA levels in patients with disseminated prostatic
      carcinoma. METHODS: 26 patients with disseminated prostatic carcinoma treated
      with megestrol acetate were followed for 21 months to determine its effects on
      testosterone, dehydroepiandrosterone and PSA levels. RESULTS/CONCLUSIONS: We
      observed a testicular and adrenal antiandrogenic effect. Patient clinical course
      improved when PSA levels dropped, although this improvement was not related with
      changes in androgen levels.

PMID- 9586314
TI  - [Lithiasis in megacalyosis].
AB  - OBJECTIVE: To review our series of lithiasis associated with megacalyosis, a rare
      disease entity. METHODS/RESULTS: The clinical records of patients treated from
      1976 to 1994 were reviewed. Of 39 cases of megacalyosis, 27 were associated with
      lithiasis and was slightly more prevalent in males (59.3%). Struvite and
      whewelite calculi were more prevalent and 40.7% also had urinary tract infection,
      E. coli, Pseudomonas and Proteus being the most frequent pathogens. ESWL with
      hyperhydration was the most frequently utilized treatment. CONCLUSIONS:
      Megacalyosis is an embryogenic anomaly of Malpighi's pyramids that is associated
      with lithiasis in 69.2% of our series, frequently localized to the left side. We
      have found no significant difference according to sex or a hereditary component.
      IVP is the principal diagnostic method for megacalyosis. The frequent association
      of urinary tract infection should be taken into account when instituting
      treatment.

PMID- 9586315
TI  - [What information can radiodiagnostic media give us when recurrent urinary
      infections in childhood are caused by functional pathology and anatomic
      anomalies?].
AB  - OBJECTIVE: To analyze the alterations of the radiologic studies in children with
      recurrent urinary tract infection without urinary tract organic abnormalities.
      METHODS: The present study comprised 50 children (8 boys, 42 girls) aged 4 to 36
      months (mean 16 months). Patient evaluation included diagnostic voiding
      cystourethrogram, ultrasonography and intravenous urography. RESULTS: Voiding and
      filling cystourethrography were performed in all cases, which demonstrated a
      trabeculated bladder (like fringes in the bladder wall); 35 of the 50 children
      had small bladders; 15 of the 50 children had a normal or bigger, but flaccid
      bladder. Forty-four children showed signs of intermittent obstruction in the
      posterior urethra during the voiding phase. The intravenous urogram showed a
      small bladder with different degrees of trabeculation and residual urine in 15 of
      38 cases. CONCLUSIONS: Radiologic diagnostic studies can discard organic
      abnormalities of the urinary tract and can be useful un detecting a possible
      functional disorder.

PMID- 9586316
TI  - [Neurobiology of erectile dysfunction in multiple sclerosis].
AB  - OBJECTIVE: To analyze the neurological alterations responsible for impotence in
      multiple sclerosis. METHODS: We conducted a pharmacologic erection test and a
      neuroandrologic profile study in 11 patients with multiple sclerosis and
      impotence. This study consisted in: bulbocavernosus EMG, S2-S4 evoked potentials,
      somatosensory potentials of pudendal nerve, electromyography of cavernous smooth
      muscle (SPACE), sympathetic skin response (SSR) and cystometry. RESULTS: The most
      frequent neurological lesion was complete suprasacral (7 cases; 64%) and
      parasympathetic (7 cases; 64%) lesions. The parasympathetic lesions were of the
      upper motor neuron type in 6 of the 7 cases (86%). Peripheral autonomic
      [sympathetic in 2 cases (18%); parasympathetic in 1 case (9%)] and pudendal
      lesions (3 cases; 27%) were also observed. CONCLUSIONS: The main cause of
      impotence in multiple sclerosis could be ascribed to a suprasacral lesion. Some
      cases also present peripheral autonomic lesions.

PMID- 9586317
TI  - [Clinical evaluation of the use of propoleum in Peyronie's disease].
AB  - OBJECTIVE: To analyze the clinical efficacy of propoleum in Peyronie's disease.
      METHODS: A controlled, double-blind clinical trial based on a previous pilot
      study was conducted in 34 patients with Peyronie's disease treated with propoleum
      (Cuban Academy of Sciences patent no. 21875). The study was performed at the
      Freyre de Andrade Hospital in Habana. The clinical course and ultrasound features
      of the fibrous plaque were evaluated during a period of 6 months. RESULTS: A
      marked improvement was observed for penile curvature and pain in the treated
      group. Furthermore, plaque consistency and size was reduced five-fold after
      treatment and two-fold at ultrasound evaluation. No clinical or ultrasound
      changes were observed in the control group. CONCLUSIONS: Our results demonstrate
      the efficacy of propoleum in Peyronie's disease.

PMID- 9586318
TI  - [Orthotopic bilateral ureterocele].
AB  - OBJECTIVE: To describe two additional cases of bilateral orthotopic ureterocele
      and review the literature. METHODS/RESULTS: Both patients, a 70-year-old male and
      a 56 year-old female, were diagnosed by IVP. Treatment was by a bilateral
      transverse "smile" incision, which achieved good functional results. However, one
      of the patients with a calculus inside both ureteroceles developed unilateral
      grade II-III vesico-ureteral reflux. CONCLUSIONS: Despite the risk of developing
      vesicoureteral reflux, the transurethral transverse incision is a good method of
      treatment in symptomatic bilateral orthotopic ureterocele.

PMID- 9586319
TI  - [Primary renal lymphoma. Apropos of a case].
AB  - OBJECTIVE: To describe case of primary renal lymphoma. METHODS/RESULTS: A 76-year
      old female patient with a diagnosis of a left renal mass was referred to our
      service. The patient underwent a radical nephrectomy. Histological analysis of
      the surgical specimen revealed a non-Hodgkin lymphoma. She received combination
      chemotherapy with CHOP. CONCLUSIONS: Primary renal lymphoma is a rare clinical
      entity whose existence has been questioned very often. Its clinical presentation
      is not unlike that of any other renal tumor and its diagnosis is by histology.
      Although it is a rare tumor type, it must be taken into account when making the
      differential diagnosis of any renal mass. Surgical resection in combination with
      chemotherapy with or without radiotherapy continues to be the widely utilized
      treatment for primary renal lymphoma.

PMID- 9586320
TI  - [Bladder malacoplakia: apropos of 2 cases].
AB  - OBJECTIVES: To describe two cases of malakoplakia of the bladder with an unusual
      form of presentation and review the cases previously reported in the literature.
      METHODS/RESULTS: Two patients, a 61-year-old female and a 71-year-old male, are
      described. Both patients had a history of recurrent infection caused by coliform
      pathogens. Treatment consisted of trimethoprim sulfamethoxazole, ascorbic acid
      and bethanecol chloride, together with extended TUR of the bladder lesion.
      CONCLUSIONS: Although malacoplakia of the bladder is considered to be a benign
      disease, close follow-up is warranted due to frequent recurrence of symptoms and
      the difficulty in achieving long-lasting effects since it is frequently
      associated with immunosuppression.

PMID- 9586321
TI  - [Testicular infarct simulating a neoplasms].
AB  - OBJECTIVE: The diagnosis of torsion of the spermatic pedicle is primarily
      clinical, despite the reports concerning the utility of complementary studies. A
      case of testicular infarct is described herein. METHODS: A 22-year-old patient
      consulted for swelling and pain referred to the left testicle. Scrotal ultrasound
      revealed hypoechoic areas alternating with hyperechoic areas and thickening of
      adjacent scrotal tissue. These non-specific findings suggested a misleading
      diagnosis of a tumor. The patient was submitted to radical orchidectomy.
      CONCLUSIONS: Scrotal ultrasonography can be misleading in cases of chronic
      testicular torsion. In equivocal cases, early surgical exploration may be
      required to discard testicular torsion and unnecessary orchidectomy.

PMID- 9586322
TI  - [Prostatic xanthoma].
AB  - OBJECTIVE: To describe a case of prostatic xanthoma, a benign condition of
      inflammatory origin related with granulomatous prostatitis. METHODS: A 70-year
      old patient with voiding syndrome and a DRE suggestive of grade II hyperplasia of
      the prostate is described. A bilateral biopsy of the prostate was negative. The
      patient was submitted to transurethral resection with normal analytical data.
      Histological examination of the specimen showed benign prostatic hyperplasia
      associated with sclerosing adenosis and a clear, foamy cytoplasmic cell and an
      unremarkable nucleus. Immunocytochemical analysis with the KP-1 lysosomal marker
      (CD-68) disclosed macrophages. Cytokeratin labelling (AE1-AE3) was negative,
      thereby discarding any type of epithelial cell proliferation. CONCLUSION: Due to
      its rarity, making the differential histological diagnosis of prostatic xanthoma
      can be difficulty in certain cases and it can occasionally present as a palpable
      mass. However, it must be emphasized that it is a benign condition and clinically
      irrelevant in most of the cases.

PMID- 9586323
TI  - [Adrenal hemangioma of atypical presentation. Bibliographical Review].
AB  - OBJECTIVE: To report a case of adrenal hemangioma presenting as spontaneous
      massive retroperitoneal hemorrhage that required surgical treatment without
      preoperative hormonal study. METHODS/RESULTS: Due to the intense pain and
      hemodynamic instability, the patient described herein was immediately submitted
      to laparatomy, adrenalectomy and drainage. The literature is reviewed with
      special reference to the clinical and radiological findings that could permit
      making a correct preoperative diagnosis. To our knowledge, a similar form of
      presentation has not been reported in the literature. The patient is asymptomatic
      8 months postoperatively. CONCLUSIONS: Adrenal hemangioma is a rare tumor that
      usually presents as an incidental finding or with chronic pain in the abdominal
      flank. Although it is rarely malignant and some authors advocate conservative
      management based on the radiological findings, the difficulty lies in the similar
      evolution of other adrenal tumors that can produce similar findings. We therefore
      advocate surgical excision of adrenal incidentalomas due to their indeterminate
      histological and clinical behaviour.

PMID- 9586324
TI  - [Tethered cord syndrome in the adult].
AB  - OBJECTIVES: To describe a case of tethered cord syndrome, with special reference
      to the diagnostic and therapeutic difficulties. METHODS: A case of an adult
      patient with tethered cord syndrome after the complications post-TURP is
      described. The most relevant radiological and urodynamic features are presented.
      CONCLUSIONS: The tethered cord syndrome in the adult has a wide variety of
      symptoms. The age of onset depends on the level of cord involvement and the
      precipitationg factors. The urological symptoms are as varied as the urodynamic
      features, therefore each case must be treated independently. Treatment is a
      controversy; untethering offers little benefit to the patients. The incidence of
      the tethered cord syndrome in the adult may be higher than the reported
      incidence, particularly in patients with progressive and unexplained
      neurological, orthopedic or urological symptoms.

PMID- 9586325
TI  - KI67 proliferation index in tumors of the upper urinary tract as related to
      established prognostic factors and long-term survival.
AB  - OBJECTIVE: Nephroureterectomy is the standard treatment for tumors of the renal
      pelvis and ureter. Conservative management or indication of adjuvant treatment in
      these neoplasms is based mainly in histological grade and stage. The aim of this
      study is to assess the relation of Ki67 index with other established prognostic
      factors and to define its predictive value for long term survival, which could be
      useful in selecting the best treatment for each individual case. METHODS: 81
      patients with urothelial tumors of the renal pelvis and ureter, diagnosed and
      treated between 1975 and 1993, comprised the present study. Ki67 immunostaining
      was performed in paraffin-embedded tissue. A cut-off limit of 20% was chosen.
      Tumor location, histological grade, histological pattern, local (T), nodal (N),
      vascular and perineural invasion and stage (TNM) were assessed in relation to the
      proliferation index and as prognostic criteria for survival in both univariate
      and multivariate analysis. RESULTS: The Ki67 proliferation index was found to be
      related to grade (p < 0.001), T (T0 vs T1-4; p < 0.01), N (p < 0.038), TNM
      categories (stage 0 vs I-IV; p < 0.048) and perineural invasion (p < 0.01). There
      was a marginal relation to vascular invasion (p < 0.11). Survival was better for
      the patients with low proliferating tumors (90%) than for high proliferating ones
      (67%) (p < 0.02). In the multivariate analysis only T stage was statistically
      significant (p < 0.01) but a highly suggestive trend was found for the Ki67 index
      (p < 0.07). CONCLUSIONS: Tumor proliferation assessed by Ki67 immunostaining is
      related to the progression of the disease and proved to be of predictive value
      for long-term survival in tumors of the renal pelvis and ureter. The Ki67 index
      is able to detect high-risk patients that could not be cured by radical surgery
      alone, raising the need for some type of aduvant treatment in these cases. The
      treatment predictive effect observed in low grade-low stage cases suggests its
      possible utility in patients managed conservatively.

PMID- 9586326
TI  - [The genus Enterococcus: its pathogenicity, virulence and antibiotic resistance.
      The molecular genetics elements (I)].

PMID- 9586327
TI  - [The characteristics of the viruses involved in avian respiratory diseases and
      some bird-man epidemiological correlations].

PMID- 9586328
TI  - [Rapid diagnosis in tuberculosis by using the MB/BacT system].
AB  - 428 clinical samples were examined by the MB/Bact system and by inoculation on
      "Tebeglut" medium. 43.9% of the samples were positive for Mycobacterium sp. when
      examined by MB/BacT system and 29.6% when cultivated on Tebeglut. The reported
      percent of positivity (43.9%) is highly superior if compared with those reported
      in other countries: Great Britain (9.1%), France, (7.0%). The MB/BacT system is
      much more effective in detecting mycobacteria if compared with Tebeglut
      cultivation, mainly in two categories of samples: those with no evidence of AARB
      and those with fewer than 10% AARB. From 156 Mycobacterium sp. isolated in
      MB/BacT system, 88.5% were M. tuberculosis, the others being atypical
      mycobacteria.

PMID- 9586329
TI  - [A comparative study between the results of the bacteriological diagnosis of
      blood cultures performed by the classic method and in the BacT/Alert system].

PMID- 9586330
TI  - [The chemosensitivity of strains of Vibrio cholerae group O1 isolated in Romania
      between 1977-1995].

PMID- 9586331
TI  - [The in-vitro antifungal activity of ortho-phenanthroline].

PMID- 9586332
TI  - [Immunological studies by phenotyping tests and functional analysis at the
      cellular level in populations of children from 2 different communities (Targu
      Mures and Ploiesti)].

PMID- 9586333
TI  - [The importance of lymphocytic immunophenotyping in the clinical and therapeutic
      monitoring of acute joint rheumatism in school-aged children].

PMID- 9586334
TI  - [The usefulness of determining acute-phase reactants in establishing the
      bacterial etiology in lower respiratory tract infections].

PMID- 9586335
TI  - [The use of inactivated polio vaccine to prevent polio paralysis associated with
      the vaccination of children living in orphanages].

PMID- 9586336
TI  - [The measles epidemic in 1996-1997 in Romania: an analysis of surveillance data.
      The options for the control of measles epidemic contingencies in a highly
      vaccinated population].

PMID- 9586338
TI  - [Current methodologies and the outlook in the diagnosis of of tuberculosis].

PMID- 9586337
TI  - [The importance of immunological markers in the diagnosis of central nervous
      system infections produced by mycobacteria].

PMID- 9586339
TI  - [Cellular immunity in tuberculosis].

PMID- 9586340
TI  - Race-related stress among Asian American veterans: a model to enhance diagnosis
      and treatment.
AB  - This article addresses theoretical principles and clinical descriptions of the
      phenomenon of race-related stress and trauma experienced by Asian American
      Vietnam veterans. A conceptual model of race-based stress is presented, comprised
      of five principles, by which to understand mental health difficulties that can
      arise in regard to race-based stressors. The model describes (a) the relationship
      between life threat and physical similarity to the "enemy," (b) the relationship
      between fear and prejudice, (c) dehumanization as it impacts race hate and combat
      indoctrination, (d) additive life threat related to exploitation of one's
      physical similarity to the "enemy," and (e) race-based remorse. The article
      delineates factors affecting treatment seeking and disclosure of race-based
      stresses, guidelines for interviewing veterans about race-related events and
      ethnic self-worth, and the harmful effects of race hate.

PMID- 9586341
TI  - The healing power of culture stories: what writers can teach psychotherapists.
AB  - The personal narrative as the shared story of one's life in cultural context is
      increasingly being viewed by psychotherapists as a useful way to support the work
      of healing. This article uses the life course narratives of creative writers,
      especially those who write from outside the margins of the dominant culture, as
      shared resources for growth. The article focuses on Isabel Allende's book Paula,
      which tells the story of how the experienced her daughter's death as both a
      shattering below and a life-expanding opportunity to revisit her lifelong
      storehouse of relationships and cultural resources. Out of these narratives, she
      drew new strengths and insights that helped her cope with her loss and create a
      new relationship with her daughter's spirit. The article suggests how
      psychotherapists concerned with honoring the complexity of culturally diverse
      life stories can learn to use personal narratives as resources for healing, for
      ourselves and with others.

PMID- 9586342
TI  - Preferences of old and young Navaho Indians for Western and indigenous health
      care providers: an exploratory study.
AB  - References for Western versus traditional health care providers were assessed in
      27 older (M = 61.5 years) and 21 younger (M = 22.6 years) American Indians living
      on the Navaho reservation. Participants were read standardized vignettes
      depicting diagnosable physical and emotional illnesses, and they completed a
      series of forced-choice questions indicating their preference for traditional or
      Western health care providers for treating these conditions. Analysis of variance
      (ANOVA) was used to assess health care provider preference with age, interviewer,
      and illness type as independent variables. Medical doctors were preferred over
      all other health care providers for physical problems, and this was particularly
      true for the younger group. Although it was anticipated that the older
      participants would favor traditional healers and the younger participants would
      prefer Western options, there was no main effect for age. This lack of
      differentiation by age in provider preference was interpreted in terms of
      informal utilization patterns and the role of the family referral system inherent
      in this group of indigenous adults.

PMID- 9586343
TI  - Psychosocial adjustment among Central American immigrants with disabilities: an
      exploratory study.
AB  - This is an exploratory study that investigated factors influencing the
      psychosocial adjustment of Central American immigrants with disabilities. The
      relationships between stress, and perception of disability severity and (a)
      depression and (b) anxiety were assessed. Furthermore, this study investigated
      whether social support moderated the impact of stress and severity of disability
      on depression and anxiety. Stress, severity of disability, and social support
      explained a high percentage (54%) of the variance in depression. High levels of
      stress, increased perceptions of severity of disability, and low social support
      were associated with increased depression. The interactions between support and
      stress and between support and disability severity did not significantly add to
      the original model which predicted depression. Main effects were found for
      stress, disability severity, and the interaction between support and disability
      severity. Stress and social support significantly accounted for 31% of the
      variance in anxiety. Increased stress and decreased social support were
      associated with greater levels of anxiety. The interaction between support and
      stress did not significantly predict anxiety. Implications of the study in terms
      of future research and intervention programs targeting mental health outcomes for
      Latino immigrants with disabilities are discussed.

PMID- 9586344
TI  - Cultural intersections and systems levels in counseling.
AB  - A clinical case is presented in which a systemic approach to psychotherapy was
      used. This approach to clinical work is crucial in that the interactive pattern
      of social and institutional relationships is seen as the context for treatment.
      Systems theory allows the clinician to move away from a cultural way of thinking
      about clinical work focused on the individual, and instead views the individual
      in interaction with multiple systems as the focus for clinical intervention. This
      case study illustrates the nature of systemic work by demonstrating four levels
      of systems that have an impact on work with the patient: the individual level,
      the family systems level, the clinic system level, and the agency level. The case
      highlights how therapists in training might consider the context of larger
      systems that influence the environmental and psychological factors in their
      patients' lives.

PMID- 9586345
TI  - Coming out in primetime: the mental health impact of Ellen's "debut".

PMID- 9586346
TI  - Regulation of mouse NK cells by structurally divergent inhibitory receptors.

PMID- 9586347
TI  - Stimulatory receptors in NK and T cells.

PMID- 9586348
TI  - Killer cell inhibitory receptor expression by T cells.

PMID- 9586349
TI  - The CD94/NKG2 C-type lectin receptor complex.

PMID- 9586350
TI  - Triggering of natural killer cell mediated cytotoxicity by costimulatory
      molecules.

PMID- 9586351
TI  - Fc receptors on natural killer cells.

PMID- 9586352
TI  - Adhesion in NK cell function.

PMID- 9586353
TI  - Signal transduction during NK cell activation: balancing opposing forces.
AB  - Significant progress has been made in our understanding of the basic signaling
      mechanisms regulating NK cell activation. Advances have been fueled in part by
      the molecular characterization of specific activating receptors (e.g., the Fc
      gamma RIII multi-subunit complex) and inhibitory receptors (e.g., novel MHC
      recognizing inhibitory receptors). However, certain aspects of these analyses are
      complicated by the heterogeneous nature of the receptor-ligand interactions
      utilized during the development of a cytotoxic response. Future advances will
      depend in part on the further molecular characterization of the involved
      receptors and second messengers and on the development of experimental models for
      genetically manipulating the signaling elements. It will remain important to
      understand both activating and inhibitory signaling pathways as the emerging
      theme is that the balance of these two opposing forces determines the functional
      outcome of an NK cells interaction with its target.

PMID- 9586354
TI  - Effector pathways of natural killer cells.

PMID- 9586355
TI  - Toward a quantitative analysis of the repertoire of class I MHC-specific
      inhibitory receptors on natural killer cells.

PMID- 9586356
TI  - Ontogeny and differentiation of murine natural killer cells and their receptors.

PMID- 9586357
TI  - Control of infections by NK cells.

PMID- 9586359
TI  - [Prevention of catheter infections. Has the time to change come?].

PMID- 9586358
TI  - Natural killer cells and tumor therapy.
AB  - Evidence has been reviewed which indicates that NK cells play a role in the
      control of metastasis dissemination. Both activation of endogenous NK cells in a
      tumor-bearing host and adoptive transfer of ex vivo activated NK cells may be
      therapeutically beneficial. The small number of phase I/II clinical trials of AIT
      with A-NK cells performed in patients with cancer so far does not allow firm
      conclusions, except to ascertain the feasibility and a lack of toxicity of this
      form of therapy. Although numerous trials have been performed with BRMs, many of
      which are known to upregulate NK activity in vivo, a general lack of correlations
      between clinical responses or survival and upregulated NK activity in the
      peripheral blood has dampened enthusiasm for biological therapies. However, these
      clinical trials have been confined largely to patients with advanced metastatic
      disease. It is highly likely that tumor-induced immunosuppression plays a crucial
      role in neutralizing the benefits of BRM therapy, and that levels of effector
      cell activation sufficient for metastasis elimination are seldom achieved in this
      clinical setting. On the other hand, administration of BRMs in the adjuvant
      setting could be more effective and when combined with monitoring for effector
      cell functions might perhaps provide a better guide for achieving the levels of
      endogenous NK activity necessary for elimination of remaining or occult
      metastases. An improved understanding of NK cell biology in cancer patients is
      likely to serve as a positive reinforcement for design of a new generation of
      clinical trials incorporating novel approaches to NK cell mediated cancer
      therapy.

PMID- 9586360
TI  - [Virus-specific serum and fecal antibodies response in children with acute
      rotavirus gastroenteritis].
AB  - BACKGROUND: The analysis of the immune response to rotavirus infection and the
      characterization of the viral antigens recognized by specific antibodies are of
      great concern in evaluating the protection against rotavirus. MATERIAL AND
      METHODS: The levels of rotavirus-specific fecal (sIgA) and serum antibodies (IgM,
      IgG and IgA) were evaluated by ELISA in 25 children with acute gastroenteritis
      for rotavirus, in 11 of them during the acute and convalescent phases. The
      specificity of serum antibodies to viral polypeptides was characterized by
      immunoblotting. RESULTS: Serum IgM antibodies with a geometric mean titer (GMT)
      of 1/3,973 were the predominant antibodies detected during the acute phase. In
      comparison, IgG and IgA serum antibodies and sIgA coproantibodies levels were
      higher in the convalescent phase (GMT = 1/5,799, 1/257 and 1/137 respectively).
      Significant differences were observed for all the isotypes of immunoglobulins
      evaluated during the infection and in the convalescence (p < 0.01). Rotavirus
      specific serum antibodies recognized mainly the structural VP6, VP7 and VP3/VP4
      proteins. Other polypeptides also detected were VP1, VP5 and the non-structural
      NS34 protein. CONCLUSIONS: Rotavirus infection produce an intense humoral immune
      response both in serum and in the gut. Specific antibodies react against
      structural proteins of the internal (VP6) and external (VP7) capsids of
      rotavirus.

PMID- 9586361
TI  - [The usefulness of abdominal echography in the diagnosis of extrapulmonary
      tuberculosis in patients with HIV infection].
AB  - BACKGROUND: The aim of the present study was to analyze the diagnostic
      profitability of echography as an indicator of extrapulmonary tuberculosis in
      patients with HIV infection. PATIENTS AND METHODS: HIV positive patients
      presenting fever of long duration were prospectively studied with an active
      search for specific echographic lesions. Descriptive statistics were performed by
      variance analysis. The diagnostic profitability of echography was evaluated by
      the calculation of sensitivity, specificity, positive predictive values (PPV) and
      negative predictive value (NPV). RESULTS: Criteria of prolonged fever was
      fulfilled by 116 patients. Thirty-five (30.2%) presented specific echographic
      alterations: 12 had multiple hyoechoic splenic lesions (34.3%), 11 abdominal
      adenopathies (31.4%), 9 splenic lesions and adenopathies (25.7%) and 3 showed
      hepato-splenic involvement and adenopathies (8.6%). The final diagnoses of these
      patients were: one case of toxoplasmosis, 2 MAI infection, 7 with no definitive
      diagnosis, and 25 (71.4%) tuberculosis. The mean CD4 lymphocyte count was 46.6 x
      10(6)/L in patients with tuberculosis with no echographic findings, with a
      statistically significant difference of p < 0.05. The appearance of some
      echographic alterations had a global sensitivity of 37.3%, a specificity of 79.6%
      a PPV of 0.65 and a NPV of 0.51. The isolated findings of hypoechoic splenic
      lesions showed a sensitivity of 19.23%, a specificity of 95.12%, a PPV of 0.83
      and a NPV of 0.47. CONCLUSIONS: The presence of multiple hypoechoic splenic
      lesions showed an elevated specificity, being greater than 95%, making this
      finding, although infrequent, that of greatest diagnostic profitability in the
      echographic study of tuberculosis. We therefore consider abdominal echography to
      be of great usefulness in the evaluation of patients with HIV infection and
      prolonged fever since the presence of these lesions, in the most severely
      immunosuppressed patients, may strongly suggest the diagnosis of extrapulmonary
      tuberculosis.

PMID- 9586362
TI  - [Outbreak of nosocomial diarrhea by Clostridium difficile in a department of
      internal medicine].
AB  - BACKGROUND: Clostridium difficile (DCD) is the main etiologic agent of nosocomial
      diarrhea of infectious origin. Most of the cases of DCD have been detected in a
      hospital environment. PATIENTS, MATERIAL AND METHODS: From October to November
      1996 five cases of nosocomial diarrhea were detected with the presence of the
      toxin A of Clostridium difficile being observed in the stools. These patients
      were compared with a group of 19 patients without diarrhea (controls) who were
      admitted to the same ward during the same period as the patients with DCD.
      RESULTS: The hospital stay of the cases was greater (25 +/- 8 days) than that of
      the controls (14 +/- 10 days; p < 0.05). One hundred percent of the cases
      received antibiotics during admission (2 +/- 1.2 antibiotics per patient), versus
      68% of the controls (1.1 +/- 0.9 antibiotics per patient, p > 0.05). The length
      of antibiotic treatment prior to the onset of the symptoms was 8 +/- 3 days
      (range 7-11 days). The type of antibiotic administered was similar in both
      groups. More of the cases with DCD (60%) had vesicle catheterization than the
      controls (11%, p < 0.05). All the patients with DCD presented abdominal pain and
      several liquid stools per day without blood or pus (3.2 +/- 0.45 stools per
      patient) and 2 (40%) fever. The mean length of diarrhea was 5.6 +/- 3.6 days. The
      serum albumin concentration on the first day of admission was significantly lower
      in the cases of DCD (2.9 +/- 0.4 mg/dl) than in the controls (3.3 +/- 3.4 mg/dl,
      p < 0.05). All the cases received antibiotic treatment for Clostridium difficile
      (oral metronidazol or vancomycin) with good clinical evolution. CONCLUSIONS: The
      patients with DCD had more often had vesicle catherization and presented a lower
      serum albumin concentration than the controls.

PMID- 9586363
TI  - [The experience of the search for Lyme disease in the eastern Canary Islands].
AB  - BACKGROUND: The eastern region of Canary Islands presents certain climatic and
      atmospheric conditions which differentiate it from the accepted parameters in
      cases of Lyme disease. We present a serologic study of patients with clinical
      syndrome which is potentially compatible with Lyme disease, in an effort to
      clarify the presence of this disorder region. MATERIAL AND METHODS: We assayed
      type IgG and IgM antibodies against the flagellin antigen of the native Borrelia
      burgdorferii using indirect enzymeimmunoassay (EIA) as a screening technique. In
      the serum presenting positive screening we confirmed this result with immunoblot
      (IB) type IgG and/or IgM with synthetic peptides for the antigenic epitopes p14,
      p41, p100, OspA and OspC. We review the clinical history of the patients with
      reactive sera. RESULTS: We studied a sample group of 1,452 patients considered
      clinically compatible with Lyme disease over a 42-months period, presenting the
      screening results for serologic positive 47 (3.2%). From this sample, 24 (1.65%)
      were IB reactive, independent of the type of immunoglobulin. Only two fulfilled
      the criteria of both IB-IgM positive, one with antibodies against OspC and p41
      proteins finally diagnosed as arteriosclerotic encephalopathy suboccipital
      Binswanger and another with antibodies against p100 and p41 proteins, diagnosed
      as presenting a primary cytomegalovirus disease. The bands that, most often lead
      to reactive IB were p41 and p14. Of the 24 patients who presented reactive IB, 14
      (58.3%) also presented other previous data wich produced the false positives, 8
      with autoimmune disease, 5 viral infectious and one infection due to Treponema
      pallidum. CONCLUSION: Due to the lack of studies carried out in this field which
      would verify or rule out an epidemiologic chain in our region, our serologic and
      clinical data put the eastern Canary Islands in doubt as an endemic area of Lyme
      disease.

PMID- 9586364
TI  - [The first description of infection by Actinomyces radingae].
AB  - BACKGROUND: To communicate at clinical value of an isolation of Actinomyces
      radingae from an ulcerated lesion the external supra-malleolus region. MATERIAL
      AND METHODS: We proceed to study the clinical and bacteriological value of an
      isolated aerobic gram positive rod in pure culture obtained from an ulcerated
      lesion ocated at the external supra-malleolus region of a 92 years old woman in
      whom there was later evidence of an epidermoid carcinoma. Surgical and antibiotic
      treatment were needed. The biochemistry characterization of the isolated was
      carried out according to the schemes of Weaver-Hollis and Funke et al, as well as
      the characterization of the fat acids of their cellular wall by gas-liquid
      chromatography. RESULTS: The isolated was identified as Actinomyces radingae. The
      patient follow-up was satisfactory after the treatment. CONCLUSION: The first
      infection description by Actinomyces radingae is reported wherein its
      pathological value is evident as it is isolated in pure culture.

PMID- 9586365
TI  - [The etiology of nosocomial infection in surgery: comparison of 2 years (1988 and
      1996)].
AB  - BACKGROUND: Nosocomial infections (NI) make up an important problem in Public
      Health Care. From an etiologic point of view they are characterized by their
      constant evolution over time. Thus, the aim of this study was to know the
      etiologic variations of NI in the surgery departments of a university hospital.
      MATERIAL AND METHODS: Active surveillance of NI in the departments of general,
      vascular and urologic surgery was undertaken in 1988 and 1996. The frequency of
      the presentation of different microorganisms was globally calculated and based on
      the localization of the infection. RESULTS: At present, the most important
      microorganisms were E. coli (20.6%), Enterococcus sp. (15.6%), S. epidermidis
      (8.8%), Streptococcus sp. (8.5%), other negative coagulase staphylococci (NCS)
      (5.7%), Pseudomonas sp. (5.5%), S. aureus (5.2%), and Candida sp. (4.3%). On
      analysis of the temporal evolution an increase was observed in gram positives
      (27.4% in 1988 and 46.4% in 1996). Enterococcus sp. increased in surgical
      infections (5.8% in 1988 and 15.8% in 1996) and in the urinary tract (8.5% in
      1988 and 25.6% in 1996). Contrary to the S. epidermidis, the NCS increased in
      importance mainly in infections at the site of surgery (0% in 1988 to 5.1% in
      1996). The appearance of Klebsiella sp., Enterobacter sp. and Proteus sp.
      decreased. CONCLUSIONS: A great variation was observed in the etiology of
      nosocomial infections in surgery departments not only over time but also based on
      the localization of the infection. In recent years gram positive infections have
      increased with a rise in the incidence of staphylococci, streptococci and
      enterococci, in addition to greater protagonism by Candida sp.

PMID- 9586366
TI  - [The usefulness of a selective disk-broth media for the detection of group B
      streptococci in the vagina].
AB  - BACKGROUND: The detection of pregnant group B streptococci (GBS) carriers allows
      intrapartum administration of antibiotic prophylaxis to these women and prevents
      perinatal infection by this microorganism. The aim of this study was to determine
      the usefulness of a selective media to detect GBS in the vagina based on the disk
      broth method. MATERIAL AND METHODS: One thousand six hundred five vaginal swabs
      were seeded in blood agar with colistin and nalidixic acid (NDA) and in a
      selective disk-broth tube consisting of 2 ml of Mueller-Hinton broth with 5%
      serum and a disk of 30 micrograms of amikacin which was reseeded at 24 hours of
      incubation in blood agar with NDA. RESULTS: GBS was isolated by either of the two
      methods in 209 samples (13.0%); in 160 (9.9%) in the initial dish of blood agar
      with NDA and in 205 (12.7%) in the subculture of the selective disk-broth media.
      CONCLUSIONS: The selective disk-broth media used in this study is a simple method
      which allows detection of GBS in vaginal samples of women with GBS cultures in a
      negative agar blood dish.

PMID- 9586367
TI  - [Criteria of the MENSURA group for the definition of the critical points of
      sensitivity to antibiotics].

PMID- 9586368
TI  - [Parapharyngeal abscess in an immunocompetent patient].

PMID- 9586369
TI  - [Pneumonia of torpid evolution in a 65 year-old patient].

PMID- 9586370
TI  - [Infectology of infectiology? A modest proposal].

PMID- 9586371
TI  - [Bacteremia by Sphingomonas paucimobilis].

PMID- 9586373
TI  - [Breast abscess by Nocardia asteroides in an immunocompetent patient].

PMID- 9586372
TI  - [Primary meningococcal pericarditis by meningococcus serogroup B].

PMID- 9586374
TI  - [Cutaneous sporotrichosis in a 78 year-old man].

PMID- 9586375
TI  - [Subacute infectious endocarditis in prosthetic valve by Peptostreptococcus
      micros].

PMID- 9586376
TI  - [Endocarditis by Bacillus cereus 1 in prosthetic mitral valve].

PMID- 9586377
TI  - [Pharmaceutical expenses, life and purse].

PMID- 9586378
TI  - [Impact of voluntary pregnancy termination on fertility in Catalonia].
AB  - BACKGROUND: The objectives of this study are to describe the recent evolution of
      fertility since 1975 and of the abortions since 1987, and to evaluate the effect
      of abortions in the total fertility in Catalonia (Spain) in 1993. METHODS: Data
      were obtained from abortion register and live births from Instituto Nacional de
      Estadistica and from Institut d'Estadistica de Catalunya. Total fertility rate
      (TFR), modal age at childbearing (MACH) and average age at childbearing (AHUSE),
      both total and at first pregnancy were estimated using the number of live births,
      abortions and known pregnancies. RESULTS: Fertility in Catalonia has decreased
      between 1975 and 1993 from 2.73 to 1.20 children per woman. In this period the
      mean age at childbearing has also been delayed from 28.3 to 29.8 years. The
      number of abortions have increased since their legalization in 1987, being
      currently near to 10,000 per year. For every six births one abortion is informed,
      being the ratio 2 to 1 in women younger than 20 years old. The TFG estimated for
      74 the known pregnancies increases from 1.20 to 1.41 children per woman, and MACH
      is 3 months younger. CONCLUSIONS: Induced abortion has not shown a relevant
      weight to explain the low fertility rate in Catalonia in 1993.

PMID- 9586379
TI  - [Automated analysis of the quality of the minimum set of basic data. Implications
      for risk-adjusting systems].
AB  - SETTING: Together with the age of the patient, the main diagnosis, secondary
      diagnosis (comorbility and complications) and the procedures performed are the
      critical variables for risk-adjusting. Therefore, its correct incorporation to
      CMBD is of great importance. However, several studies, especially in the United
      States, but also in Spain, have made evident the existence of important problems
      of quality in these data, difficulties for its improvement and the limitations
      which this has to assess the quality or the efficiency of hospitals. The
      objective of this study is to approach the quality of administrative and clinical
      collected in the CMBD of the Valencian Health Service (VHS) using an automatized
      process of analysis of data from the same CMBD, and discuss the implications for
      its management, as well as possible improvement strategies. MATERIAL AND METHOD:
      An automatized analysis of the quality of CMBD 1994 of the VHS (20 hospitals,
      241,341 admissions) was performed, using indicators of valid fulfilling of field
      values, relationship between fields of the same episode, relationship between
      variables in different episodes and volume and specificity of clinical
      information. RESULTS: The analysed CMBD contains few errors in management
      variables, with the exception of residence, but it shows important problems of
      volume and specificity of clinical information, as well as a high variability in
      its fulfilling and quality in different hospitals. CONCLUSIONS: The quality of
      the clinical data of CMBD may be biased in its use with management aims or when
      assessing quality, as well as in epidemiological studies, evaluation of
      technology or use of services.

PMID- 9586380
TI  - [Influence of nosocomial infection on mortality in an intensive care unit].
AB  - OBJECTIVE: To evaluate the association between nosocomial infections (NI) and the
      mortality of Intensive Care Unit (ICU) patients, adjusting for the effect on
      mortality of other predictive variables. METHODS: Prospective study on 944
      concurrent patients admitted for at least 24 hours in the ICU of a tertiary level
      hospital between February and November of 1994. The association between NI
      (diagnosed using CDC criteria) and mortality was studied using multivariable
      logistic regression. RESULTS: The cummulative incidence of mortality in the ICU
      was 11.2% (CI95% = 9.9-12.5). This incidence was significantly higher in infected
      patients with a crude mortality relative risk of 2.2 (CI95% = 1.5-3.1). In the
      multivariable analysis, the effect of NI (global, pneumonias, of the urinary
      tract and bacteriemias) on adjusted mortality depended on the patient's Acute
      Pysiology and Chronic Health Evaluation II (APACHE II) score. With low APACHE II
      scores, NI was associated with an increased mortality risk. Conversely, with
      higher APACHE II scores, the relevance of NI as a determinant of mortality
      decreased and prognosis was mainly associated with the patient's severity of
      illness. CONCLUSIONS: The association between NI and mortality, adjusting for
      other prognostic factors for mortality, is confirmed.

PMID- 9586381
TI  - [Costs of accidental punctures in hospital health personnel].
AB  - OBJECTIVES: The aim of this study was to calculate the average cost of each
      hepatitis B, C and HIV follow-up carried out in the health personnel that have
      suffered an exposure to blood and body fluids and to estimate the cost for each
      of the different types of sources as well as to identify the items that account
      for the main part of the cost. METHODS: A cost analysis was carried out. The post
      exposure programme was modelled in a decision tree combining probabilities
      (percentage of each type of source in dependence of its positivity for the three
      viruses and immunization state of the health personnel against hepatitis B) and
      monetary costs (pesetas from 1994). Costs included: salaries, laboratory,
      chemist, energy, cleaning, telephone, medical and office equipment, amortization
      and lost productivity. A sensitivity analysis was carried out with the real
      fulfillment of the programme. RESULTS: The average cost was 39,564 ptas. (29,750
      ptas. applying the sensitivity analysis), with a range from 86,864 ptas. (source
      positive for the three viruses and injured subject not immunized) to 23,074 ptas.
      (source negative for the three viruses). If the source was hepatitis B positive,
      the average cost was 86,093 ptas. when the injured subject was not immunized and
      53,232 ptas. if he was immunized. Serologic tests account for the main part of
      the cost (range from 72.8% to 87.7%). CONCLUSIONS: High cost suggests an
      appropriate risk evaluation in order to avoid unnecessary follow-ups. The model
      used allows to know the cost of each potentially avoided episode and it could be
      used for any hospital in order to make an economical evaluation of new preventive
      devices.

PMID- 9586382
TI  - [Drug regulation: theory and practice].
AB  - Regulation of drugs from the public administration is an activity which is
      produced in different countries independently from the sanitary model they own.
      In the field of public financing of drugs there have been several measures to
      improve the efficiency of their use. However, the analysis of the impact of these
      measures is complex and this may justify the shortage of objectivable results,
      especially at long term. The objective of this study is to perform a systematic
      review of such measures due to the need to have information about the different
      alternatives before making a decision. The introduction of an isolated measure is
      in many cases compensated by other changes in other regulating or aiding fields
      which suggests the creation of an integral strategy which affects different
      fields (supply/demand of drugs and prescribers). It seems necessary to suggest a
      social debate taking as a basis the scientific information available at the
      moment and promote the taking of decisions which lead to a rational use of the
      available pharmacological resources.

PMID- 9586383
TI  - [Perceived quality and satisfaction and expectations study in health services].

PMID- 9586384
TI  - [Radical hysterectomy in stage 1-B-1 cervical cancer].
AB  - From 1980 to 1991 were received 6,295 patients diagnosed as invasive cervical
      cancer at the Instituto Nacional de Cancerologia of Mexico; from this group, 884
      cases were considered as stage IB (12.76%) and 133 cases, adenocarcinoma in 10,
      adenosquamous carcinoma in 6 and minimal deviation adenocarcinoma (malignant
      adenoma) in one case. Eighty percent of cases had a less than 2 cm tumor size.
      Thirteen cases had metastatic pelvic lymph nodes. Mean age 46 years (range 28-64
      years), mean operatory time 4:50 hours (range 3-15 hours), average of hemorrhage
      1,500 ml (range 300 to 5,000 ml). One patient died from no related cause. Bladder
      malfunction was observed in 8.4% and uro-vaginal fistula in 6.9% of the cases.
      Thirteen patients experimented tumor relapsing after 8 to 22 months of follow up.
      Only 3 out of 7 from that with tumor relapsing were saved with whole pelvic
      radiotherapy. One hundred-fifteen patients are alive and well after 63 months
      mean follow-up. Radical hysterectomy plus bilateral lymphadenectomy is an optimal
      surgical procedure in managing early invasive carcinoma of the cervix uteri.

PMID- 9586386
TI  - [Instrumental innovation in suprapubic microcatheter].
AB  - In this work, we introduce a new instrument for placing suprapubic catheter which
      meet all the standard for this purpose that we take in consideration. We placed
      36 suprapubic catheter in less time, made easy and without complication we
      suggest to use this instrument for better results.

PMID- 9586385
TI  - [Severe pre-eclampsia, HELLP syndrome and renal failure].
AB  - A retrospective study was done of thirty-patients with severe preeclampsia and
      HELLP syndrome whose developed acute renal failure, 25 patients also had acute
      tubular necrosis and five cases bilateral cortical necrosis with chronic renal
      insufficiency. Severe hypertension was present in all cases and anti-hypertensive
      therapy was needed. Six patients died, three due to intracranial hemorrhage,
      other two secondary to hypovolemic shock, and in one case multiple organ
      dysfunction.

PMID- 9586388
TI  - [Magnetic resonance in the diagnosis of Kallmann's syndrome. Presentation of 2
      cases and review of the literature].
AB  - The case of two women with a clinical picture of Kallmann's syndrome is reported.
      Definitive diagnosis of aplasia and hypoplasia of the olfactory bulbs was
      obtained by magnetic resonance imaging. A discussions of the clinical data and
      diagnosis approach is given. A review of available literature is also discussed.

PMID- 9586387
TI  - [Successful course of pregnancy in a patient with polyglandular Schmidt's
      syndrome treated with hormonal replacement therapy].
AB  - Schmidt's syndrome is characterized by the existence of adrenal insufficiency and
      lymphocytic thyroiditis, yet, it can also be accompanied of some other autoimmune
      diseases. Addison's disease usually produces infertility due to chronic
      anovulation, but patient who are properly treated can still be fertile. There are
      few reports of pregnancy and Schmidt's syndrome, this work presents a case
      treated with hormonal substitution therapy and successful obstetric outcome.

PMID- 9586389
TI  - [Crohn's disease and pregnancy. A case report].
AB  - The name "Inflammatory Bowel Disease", of Anglo-Saxon origin, has been worked
      wide used in the medical language to name two nosologic entities: "Ulcerative
      colitis" (CU) and "Crohn's Disease" (EC). Both affect primarily young people,
      with approximately equal male to female ratio, although there is slight
      preponderance of females. In early as 90's, the development of ulcerative colitis
      during pregnancy had been described as potentially fatal complication, based on
      this observation therapeutic abortion was frequently recommended; now a days five
      questions in these patients with Inflammatory Bowel Disease (EII) that want to
      become pregnant have to be made: 1. Will the patient have more trouble getting
      pregnant? 2. Will the same (EC) affect the prognosis of pregnancy? 3. Will
      pregnancy affect the disease? 4. Which will be the treatment of the (EC) in
      pregnant women? 5. Will the treatment affect the fetus of the pregnancy? The
      authors present a case of Crohn's disease of the colon, in a patient of 24 years
      old with her first pregnancy. This case offered the opportunity to discuss
      problems and questions that took place in this kind of circumstances as mentioned
      earlier.

PMID- 9586390
TI  - [Postabortion contraception].
AB  - In Mexico, as in almost all the Latin American countries, abortion represents an
      important maternal morbidity-mortality reason. It has been pointed out that those
      women who had an abortion, are in greater risk to repeat this condition than
      those women who have not had the episode. For this reason, it is a transcendental
      matter, the use of modern contraceptive technology for fertility regulation with
      the aim to avoid not planned pregnancies and their devastating consequences. This
      document reviews-according to the Family Planning Official Norm of the Ministry
      of Health-those different contractive alternatives, that can be used in the
      postabortion.

PMID- 9586391
TI  - [Postpartum superior longitudinal sinus venous thrombosis].
AB  - The pregnancy increases the risk of cardiovascular ischemic events, The
      longitudinal sinus thrombosis is very rare, but the incidence increases during
      pregnancy and puerperium. The mortality rates range from 25% to 50%. This report
      consists of a case which was studied and managed at the Military Central
      Hospital. It occurred on the 12th day post C-S. The diagnostic was confirmed by
      MRI. The treatment consisted of rest and heparin with a successful development.
      Our findings agreed with the studies reported at the literature that suggested a
      beneficial effect with the heparin's use, lowering drastically the mortality
      rates. Some still oppose to its use because of the risk of an intracranial
      hemorrhage.

PMID- 9586392
TI  - [Prenatal diagnosis of type II osteogenesis imperfecta].
AB  - We present one case of a 23 week old fetus that was diagnosed with osteogenesis
      imperfecta type II via ultrasound, The principal ultrasonographic findings were;
      lack of mineralization in the calvaria, short, wide, and angulated femurs, with
      the presence of fractures, the length corresponds to a 17.5 week old gestation,
      more than two standard deviations below the mean for gestational age. The rest of
      the long bones show fractures and poor mineralization that was suggested by
      reduced acoustic shadowing. An elective cesarean was programmed at 39.4 weeks of
      gestation. The osseous lesions were confirmed postnatally by means of a
      conventional radiographs.

PMID- 9586393
TI  - [D-dimer in different stages of pregnancy toxemia. A pilot study].
AB  - We assayed D-Dimer levels in the different stages of preeclampsia. This test
      appears to be the most reliable for the probability of abnormal status in
      patients with disseminated intravascular coagulation. Data were analyzed by
      dividing all cases in four groups: a.-Healthy non pregnan women (10 cases) 550
      ng/ml mean levels. B.-Normal pregnant women (8 cases) 875 ng/ml mean levels. C.
      Mild and severe preeclamptic patients (8 cases) 1625 ng/ml mean levels, and D.
      Eclampsia and HELLP patients (6 cases) 3000 ng/ml. This results were statistical
      significant at level p < 0.05. It is believed that pregnancy is associated with
      "hypercoagulability" that it is enhance in toxemia cases. It is necessary to
      perform more studies with quantitative elisa techniques of D-Dimer, more cases
      and other markers of dic and endothelial cell injury.

PMID- 9586395
TI  - [Hemostasis and antithrombotic therapy: how, when and for how long?].

PMID- 9586394
TI  - [Cornual pregnancy].
AB  - Cornual ectopic pregnancy is a rare entity, found in 2-4% of all ectopic
      pregnancies, with an estimates incidence of one in every 2500 to 5000 deliveries.
      It represents a high rate of maternal mortality because of the growth and
      secondary rupture of the zone of implantation in advanced gestational ages,
      resulting in severe hemodynamic decompensation. We realizes a retrospective study
      from January 1989 to December 1994 at Instituto Nacional de Perinatologia. Only 6
      cases of ectopic cornual pregnancies were found out of 35,080 deliveries
      reported, and of 149 ectopic pregnancies in general. Maternal age, gestational
      age at time of diagnosis, signs and symptoms, surgical treatment complications,
      and histopathologic report were some of the data collected. Maternal age in
      average was found to be 31.5, gestational age at time of diagnosis between 7.1 to
      24 weeks. All patients referred diffuse abdominal pain and amenorrhea, with 2
      cases of transvaginal bleeding. The 100% of cases required total abdominal
      hysterectomy as surgical treatment, and the most important complication found was
      shock, hence no maternal deaths were reported. We found this pathology to have an
      incidence of 1 of 5846 deliveries at our Institution, representing the 0.01% Of
      all ectopic pregnancies, we found to have an incidence of 4.02% that agrees with
      world literature.

PMID- 9586396
TI  - [Lung volumes in non-smoking healthy men in Maracaibo, Venezuela].
AB  - The significant applicability of the tests to measure lung volumes makes it
      necessary to handle them frequently and this implies the comparison of the
      registered values for lung function parameters with predicted or referential
      values which are obtained via derivate equations of healthy population studies.
      The Slow Vital Capacity (SVC), Inspiratory Capacity (IC), Functional Residual
      Capacity (FRC), Residual Volume (RV), Total Lung Capacity (TLC) and the physical
      characteristics, were measured in 50 healthy men, non smokers, with ages between
      17 and 63 years, in order to deduce++ prediction equations. The functional tests
      were performed by means of the multiple respiratory technique and Helium
      Dilution, using a Spinnaker TL Lung Functions Analyzer. Stepwise multiple
      regression analyses were used to derive equations for predicting lung volumes,
      that allowed the inclusion of the variables that add prediction with statistical
      significance (95% of confidence), and obtaining for SVC: R = 0.853, SEE = 0.350
      lts; IC: R = 0.822, SEE = 0.296 lts; FRC: R = 0.843, SEE = 0.326 lts; RV: R =
      0.891, SEE = 0.153 lts y TLC: R = 0.883, SEE = 0.458 lts. The analysis of
      variance (ANOVA) was highly significant (p < 0.00001) for each one of the models
      of regression of the estimated parameters. The fifth percentile was considered as
      the lower limit of the established volume as the normal value. The calculation of
      fifth percentiles determined were SVC = 3.59 lts, IC = 2.47 lts, FRC = 2.14 lts,
      RV = 1.26 lts, and TLC = 4.88 lts. Those values can represent the levels under
      which the test are considered as reduced. Values which are equal o greater can be
      considered as "normal" for each one of the parameters studied. The equations of
      prediction for the SVC, IC, FRC, RV and TLC can be utilized with validity and
      high confidence to calculate reference static lung volumes in our population (p <
      0.00001).

PMID- 9586397
TI  - [Development of an enzyme assay for detection of hepatitis B virus core IGM
      antibodies].
AB  - Detection of IgM anti-core (anti-HBcAg) antibodies of Hepatitis B Virus (HBV) is
      an useful marker for hepatitis B virus (HBV) acute infection. The aim of this
      study was to perform an immunodiagnostic assay for the detection of IgM anti
      HBcAg antibodies. Hepatitis B core antigen (HBcAg) was produced by a recombinant
      clone of Escherichia coli and used for the development of the immunoassay. An IgM
      capture enzyme immunoassay (EIA) was selected for the detection of IgM anti-HBcAg
      antibodies. A total of 110 human plasma or sera were tested by the capture EIA
      and a commercial assay. The capture EIA yielded 99% of sensitivity and 93%
      specificity, when compared with the commercial test. The capture EIA developed
      here is of interest for epidemiological studies, particularly for endemic regions
      in South America.

PMID- 9586398
TI  - A practical device designed to concentrate cells for cytomorphological studies of
      biological fluids.
AB  - In the present work, a device designed for concentrating cells from biological
      fluids is described. The instrument consists of a tube in which the inner cavity
      has a conical shape at one of its ends and a small orifice is found at the
      bottom, while the tube's exterior maintains its cylindrical shape. The tube is
      placed inside a second tube that ends on a flat surface on which a glass cover
      slide is placed. The sample to be studied is placed in the inner tube of the
      assembled device and spun in a regular clinical centrifuge. Cells are collected
      on the glass slide, fixed and stained for microscopical studies. The device was
      tested using 23 samples of cerebrospinal fluid (CSF) from patients with
      lymphoproliferative diseases. An adequate number of intact cells was recovered
      for observation, and a precise diagnosis was possible. Cells from three aliquots
      of each CSF sample were concentrated by this method, and by the more expensive
      standard commercial cytocentrifuge, with similar results. The device described
      here provides an easy, efficient and inexpensive method, for the concentration of
      cells from organic fluids.

PMID- 9586400
TI  - [Familial predisposition to breast cancer. Review].
AB  - An estimated 20% of all breast cancer or ovarian and breast cancer cases have
      familial aggregation. Today it is known that approximately 10% of these cases are
      attributable to inherited mutations of a predisposition gene that confers a high
      risk of developing the disease. Several genes have been identified that differ in
      the risks which they determine, the proportion of cases they explain and the
      other cancers they may cause. Out of all the genes reported so far, BRCA1 and
      BRCA2 are the most important ones. The mutations in the remaining genes are rare
      or involve moderate or low risks. The possibility to detect breast and/or ovarian
      cancer susceptibility genes in high risk families poses serious challenges that
      must be faced by health professionals related with this field.

PMID- 9586399
TI  - [Prevalence of subgroups, serotypes and electropherotypes of human rotavirus in
      Cumana, Venezuela].
AB  - From June 1992 to May 1993, rotaviruses were detected by an immunoenzymatic
      assay, in 159 (49.5%) of 321 children admitted to the hospital with acute
      diarrhea. Of the 159 cases ELISA positive, 80 samples were chosen at random to
      investigate subgroups and serotypes of group A human rotavirus. By the ELISA,
      test 9 (11.3%) of the strains were subgroup I, 46 (57.5%) were subgroup II, and
      25 (31.3%) could not be grouped. The serotype G1 was identified in 52 cases
      (65%), G2 in 11 cases (13.8%), G3 in 1 case (1.2%), and 7 cases (8.8%) showed
      more than one serotype. By electrophoretic analysis of viral RNA, 137 (42.7%) of
      the samples exhibited an RNA pattern. The long pattern (59.1%) prevailed over the
      short pattern (35.8%), and by coelectrophoresis 8 different electropherotypes
      were found throughout the period of study. These results illustrate the great
      variety of rotavirus strains in this region of the country.

PMID- 9586401
TI  - Ageing.

PMID- 9586402
TI  - Patterns of various modes of delivery in relation to presence of different risk
      factors in term pregnant mothers--a case-control study.
AB  - A case-control study, was carried out, which aimed to determine whether a
      relation exists between risk factors present in mother and the mode of delivery
      i.e., outcome. Cases were those mothers who had one or more risk factors present
      during pregnancy (namely, short stature, malpresentation, antepartum haemorrhage,
      pre-eclamptic toxaemia/eclampsia, anaemia-haemoglobin less than 10 g/dl, twins,
      bad obstetric history, prolonged pregnancy, history of previous caesarean section
      and instrumental delivery, pregnancy associated with general diseases, prolonged
      difficult labour and RH-iso-immunisation). Controls were those mothers who did
      not have any of the above mentioned risk factors. Total of 250 cases and 250
      controls were taken. Results showed that surgical and instrumental deliveries
      were strongly associated with presence of risk factors (odd's ratio: 5.94;
      attributable risks: 72%). Out of risk factors among cases, most common indication
      of caesarean section, was previous caesarean section followed by malpresentation,
      prolonged difficult labour and short statured mothers in descending order.

PMID- 9586403
TI  - Distribution of mast cells in the axillary lymph nodes of breast cancer patients.
AB  - Fifty mastectomy specimens of carcinoma breast were studied for pattern of mast
      cell distribution in their axillary lymph nodes. When all axillary nodes were
      free of tumour, the mean mast cell count was 35.75/sq mm. In the metastatic node
      the mast cell count was inversely proportional to the amount of metastatic
      tumour. The mast cell number decreased (25.64/sq mm) as the metastasis developed
      in any of the enlarged axillary nodes. Their count diminished further (23.55/sq
      mm) as the amount of metastatic tumour increased in individual nodes and when
      tumour involved all enlarged nodes. Mean mast cell count was lowest (10.50/sq mm)
      in metaplastic carcinoma. The mast cells in metastatic nodes were found mainly at
      the edges of tumour deposits.

PMID- 9586404
TI  - Aptitude of doctors about cardiopulmonary resuscitation--a survey.
AB  - Cardiopulmonary resuscitation is applied to extremely moribund cases with cardiac
      or respiratory arrest. General practitioners are mostly resuscitator outside
      hospital. With the idea to see the aptitude of this manoeuvre, 16 prefixed
      questions on this manoeuvre were selected for answers among 50 general
      practitioners. Only 2(4%) answered all the questions correctly and most (80%) of
      them answered 4 questions correctly. The results evoked a worrisome outcome. So
      it is suggested to update the practical patient care training like
      cardiopulmonary resuscitation among the doctors and paramedical personnel.

PMID- 9586405
TI  - Fibrothorax--problem, profile and prevention.
AB  - Fibrothorax is a common clinical condition found in everyday clinical practice.
      The clinical horizon of fibrothorax can be differentiated into pleural and lung
      parenchymal fibrosis. The two groups can be differentiated clinically and also by
      investigations. A thorough understanding of the process gives one better
      knowledge as to their different aetiologies, presentations and prognoses. The
      nature of prevention of this meance varies in these types. Patient's drug
      compliance status is important in preventing primary lung parenchymal fibrosis
      whereas physician's adequate care for pleural drainage is important in the
      prevention of pleural fibrosis. In this prospective study, observations were made
      on (1) the clinical presentation of 100 cases of fibrothorax and its relation to
      the primary disease, (2) aetiological distribution of the cases of fibrothorax
      and (3) scope of prevention, if any.

PMID- 9586406
TI  - Cough: an overview.

PMID- 9586407
TI  - Hallermann--Streiff syndrome.

PMID- 9586408
TI  - Subcutaneous angiolymphoid hyperplasia with eosinophilia.

PMID- 9586409
TI  - Skin.

PMID- 9586410
TI  - Auto-immune disease.

PMID- 9586411
TI  - Comparative evaluation of the cardiorespiratory effects of assist control
      ventilation vs pressure support ventilation in patients following orthotopic
      liver transplantation.
AB  - OBJECTIVE: 1) To compare the haemodynamic tolerance of ACV and PSV in patients
      mechanically ventilated after orthotopic liver transplantation; 2) to compare
      patients comfort during ACV and PSV. DESIGN: Prospective randomized cross-over
      study. SETTING: General ICU of the University of Rome "La Sapienza". PATIENTS:
      Eighteen patients admitted in ICU after orthotopic liver transplantation.
      MEASUREMENT AND RESULTS: Haemodynamic, oxygen transport and blood gas data were
      compared during an ACV and PSV trial (30'). A statistically significant decrease
      of mean pulmonary and systemic arterial pressure, PCOP, LVSWI, occurred during
      the PSV trial. PaO2 and DO2I decreased during PSV, but were still in supranormal
      range; 16 out of 18 patients described PSV as more comfortable. CONCLUSIONS: ACV
      and PSV provided a comparable haemodynamic tolerance in our patients, although
      during PSV the PaO2 was slightly decreased, probably due to decreased mean airway
      pressure (from 9.3 +/- 1.2 cmH2O during ACV to 6.6 +/- 1 cmH2O during PSV). PSV
      can be considered as a good alternative to the standard weaning techniques
      following orthotopic liver transplantation.

PMID- 9586412
TI  - [Treatment of intracranial aneurysm in interventional neuroradiology. What
      problems for the anesthetist?].
AB  - AIM: To outline the most occurring complications during endovascular treatment of
      intracranial aneurysms. DESIGN: Retrospective review of thirty-four patients
      treated from October 1994 to February 1996 with the placement of mechanically
      detachable microcoils inside the aneurysmal sac. SETTING: Interventional
      neuroradiology suite equipped for anesthetic care. PATIENTS: Thirty-four patients
      with ruptured (88%) or unruptured (12%) intracranial aneurysm submitted to
      elective (38%) or emergency (62%) endovascular treatment. Aneurysms were located
      in the anterior circulation in twenty-six patients (76%) and in the posterior
      circulation in eight patients (24%). INTERVENTIONS: A microcatheter was
      introduced into the arterial cerebral circulation to deliver tungsten microcoils
      to aneurysmal sac. The transfemoral approach was used in most cases. All patients
      were treated under general anesthesia with tracheal intubation, conventional
      mechanical ventilation and neuromuscular blockade. The procedure was performed
      under anticoagulation with heparin and intravenous nimodipine administration.
      MEASUREMENTS: Neurological assessment was performed at the time of treatment (H&H
      1) and six hours after the end of intervention (H&H 2) using Hunt and Hess
      classification system. The outcome was scored at four weeks following treatment
      using Glasgow Outcome Scale (GOS). RESULTS: Twenty-two (65%) interventions were
      successful. Attempted embolization failed in twelve (35%) patients due to
      intraoperative complications (17.6%) or technical difficulties (17.6%). Failures
      were more frequently determinated by vasospasm and haemorrhage. CONCLUSIONS: The
      time of intervention, the use of heparin and the patient medical conditions need
      to be considered in preventing the complications of endovascular treatment.

PMID- 9586413
TI  - [Evaluation by bioelectric impedance of body fluid compartments and body mass in
      cardiosurgical patients before and after total cardiopulmonary bypass].
AB  - BACKGROUND: To evaluate the influence of extracorporeal circulation (ECC) on
      fluid compartments and body mass using impedance measurements. METHODS: A
      prospective study was performed in 20 consecutive patients undergoing ECC during
      heart surgery at the Department of Heart Surgery of Verona Hospital. Resistance
      or reactance measurements at 1-5-10-50-100 KHz were performed in 20 patients
      undergoing heart surgery for valvular or coronary pathologies in class NYHA I or
      II, preoperatively and on day 1, 3 and 6 in order to evaluate total body water
      (TBW), intracellular water (ICW), extracellular water (ECW), thin and fat body
      mass. Weight, fluid-electrolytic balance and hematochemical parameters relating
      to electrochemical phenomena and the distribution of volumes in the various
      compartments, namely sodium, potassium and plasmatic osmolarity, were measured at
      the same times. Comparisons were made both between the data and during ECC.
      RESULTS: It was found that there was a mean postoperative weight gain of 2 kg in
      terms of total body water. Subsequently, this finding tended to decrease to basal
      values by day 6. Immediately after ECC, the water gain appeared to be
      predominantly extracellular, whereas the intracellular increase peaked on day 1.
      The change in total body water was correlated with the weight and fluid balance,
      but electrical measurements showed values above the corresponding weight gain.
      The duration of ECC was significantly correlated with bioelectric parameters, but
      not with absolute weight values. CONCLUSIONS: The method proved useful for the
      purpose, especially with regard to the overall population examined rather than
      individual patients. The dual-compartment electric model appears to be more
      suitable than the single-compartment model for exploring the different
      compartments. The trend of weight and total body water, which were correlated in
      pattern but not in absolute values, may be interpreted as a redistribution of
      fluids, also suggested by changes in electric parameters relating to
      compartmental distribution.

PMID- 9586414
TI  - [Description of a case of Reye's-like syndrome with fatal outcome].
AB  - A Reye Like Syndrome case occurred in a twelve year-old little girl with a
      previous familiar history is reported. The little patient was admitted in the
      pediatric ward for fever, vomiting and aspecific respiratory symptoms and
      developed very quickly a severe metabolic acidosis, alterations of consciousness,
      hypoxia, tissular hypoperfusion, multiple organ failure (MOF) and a fatal
      outcome. The postmortem diagnosis pointed out a methyl malonic acidaemia, a
      fairly frequent cause of acute metabolic distress, which may occur also in
      prepuberal age. The correct diagnostic and therapeutic approach of these cases is
      stressed since they need a prompt and careful monitoring in intensive care unit
      and a close cooperation among pediatricians, intensive care specialists and the
      nearest centre for the study of metabolic diseases.

PMID- 9586415
TI  - [Low levels of HDL cholesterol in hypothyroid patients with cardiovascular
      diseases].
AB  - BACKGROUND: Hypothyroidism is a frequent cause of hyperlipidemia, particularly in
      women, but its true prevalence, both in the general population and in
      dyslipidemic subjects, is unknown. It is uncertain if low thyroid function
      significantly influence HDL metabolism and if sub-clinical disease may cause
      metabolic abnormalities and increase cardiovascular risk. METHODS: Three-hundred
      and three consecutive female patients (mean age 59.2 +/- 0.5 yrs), observed in a
      metabolic ward because of dyslipidemia, were evaluated. RESULTS: Forty-three
      women (14.1% of the total) showed sub-clinical hypothyroidism, while in 12 cases
      (4.0%) overt hypothyroidism was diagnosed; 8 further women (2.6%) had been
      previously diagnosed to be hypothyroid and were under hormone replacement
      therapy. On the whole, hypothyroid patients showed higher mean triglyceride
      levels and lower HDL-cholesterol than dyslipidemic euthyroid women, but the
      difference did not reach statistical significance. Total cholesterol
      concentration did not change with impaired thyroid function. Hypothyroid patients
      reported a clinical history of cardiovascular disease, or had severe
      atherosclerosis demonstrated, more often than euthyroid subjects (25.0% vs 19.7%,
      p = n.s.). When only women with arterial disease were considered, HDL plasma
      levels were significantly lower in the hypothyroid than in the euthyroid group
      (44.3 +/- 3.1 vs 56.2 +/- 1.7 mg/dl, respectively; p < 0.01).
      Hypertriglyceridemia and obesity often coexisted. CONCLUSIONS: In conclusion,
      among dyslipidemic women, unrecognised hypothyroidism is highly prevalent (both
      sub-clinical and manifest). In hypothyroid subjects atherosclerosis seem to
      associate with particularly low HDL plasma levels. This might precede
      atherosclerosis development (reinforced by concomitant thyroid failure) and
      represent a marker of the polymetabolic syndrome.

PMID- 9586416
TI  - [Value of immunohistocytochemistry in the diagnosis of laterocervical masses in
      patients with a previous history of thyroid carcinoma].
AB  - BACKGROUND: The aim of this study is to evaluate the additional diagnostic
      significance of immunocytochemical staining of thyreoglobulin (TG) in Fine Needle
      Aspiration Biopsy (FNAB) of neck lymph-nodes, in patients with a previous history
      of thyroid carcinoma. METHODS: Twenty-five smears performed by ultrasound-guided
      FNAB on laterocervical nodes with a 21-23 gauge needle were evaluates. All smears
      were stained according to Papanicolaou and microscopically examined. RESULTS: Of
      these 25 smears, 15 were diagnostic and 10 were non diagnostic. Of the 15
      diagnostic cases, 10 were positive for metastatic lesions from thyroid neoplasm
      and the other 4 were classified as reactive lymphoadenitis. One smear for each
      case was selected for the immunohistochemical stain. All the 10 non-diagnostic
      cases showed no reaction to thyreoglobulin. Neoplastic cells, from 9 out of 11
      cytologically positive smears, expressed thyreoglobulin in the cytoplasm. In one
      case no reaction was evident and the other one was discarded for technical
      reasons. In 3 of the 4 cases cytologically classified as lymphoadenitis,
      immunoreactive thyreoglobulin was not found. In the fourth case, blastic-like
      cells showed a scanty cytoplasmic rime which was immunoreactive for TG and thus
      was classified as a metastatic tumour. On this basis, it is suggested that FNAB
      should be performed routinelly in the diagnostic evaluation of neck masses of
      unknown origin in patients with a previous history of thyroid neoplasm.
      CONCLUSIONS: If the FNAB is inconclusive, a second aspiration should be performed
      while immunoperoxidase stain to evidentiate TG may be an adjuntive diagnostic
      tool in cytologically negative cases.

PMID- 9586417
TI  - Hypopituitarism and antiphospholipid syndrome.
AB  - Vascular damage is a well known cause of hypopituitarism since Sheehan's report
      of postpartum pituitary necrosis; it has subsequently been reported that also
      sickle-cell anemia, eclampsia, pituitary apoplexy and other pathologies may
      induce failure of the anterior hypophysis through this mechanism. The
      antiphospholipid syndrome (APS) is characterized by widespread arterial and
      venous thrombosis with resulting different clinical features; Addison's disease
      due to adrenal thrombosis is the only endocrine involvement reported so far in
      this syndrome. We report here a case of global anterior pituitary insufficiency
      which developed soon after cerebral ischaemic stroke in a 62 year aged woman with
      Lupus aicoagulant activity (LAC) and large atrial thrombosis; underlying
      pathologies were excluded by appropriate investigations. Therefore in our opinion
      this is the first case in which anterior hypopituitarism is reported in the
      clinical constellation of APS and the second type of endocline involvement.

PMID- 9586419
TI  - [Anxiety and depression in hyperthyroidism. Psychodiagnostic investigation before
      and after medical therapy].

PMID- 9586418
TI  - [Mammary carcinoma in a patient with hyperprolactinemia].
AB  - In 1990, a 50 year-old man was referred to us for hyperprolactinemia. At 37 years
      of age the patient had undergone left mastectomy, for a histologically confirmed
      gynecomastia and, in 1989, he had undergone pituitary adenomectomy, for a PRL
      secreting macroadenoma (PRL = 3520 ng/ml). Persistently high PRL plasma levels
      (PRL = 550 ng/ml) showed an incomplete surgical removal of the adenoma and as a
      consequence, radiotherapy of the pituitary area was performed in 1990. When the
      patient referred to us, PRL plasma levels were still pathologic and medical
      therapy with bromocriptine was started. A year later a replacement therapy with
      cortisone, testosterone, L-thyroxine, was commenced, as the patient presented a
      post-radiotherapy hypopituitarism. Since the treatment with bromocriptine was
      unsuccessful, the drug was replaced with cabergoline, but not even the latter was
      able to normalize PRL plasma levels. In 1996, a nodule of 3 cm in diameter was
      discovered under his right mammary areola. The nodule biopsy showed a grade II
      infiltrating ductal breast carcinoma positive to the estrogen and progesterone
      receptors analysis. A right total mastectomy was performed and the diagnosis was
      confirmed through histological examination. A case of gynecomastia and breast
      cancer in a male patient who had been exposed to high PRL plasma levels for
      several years is reported. In this patient, both elevated PRL plasma levels and a
      relative hyperestrogenic state may have contributed to originate breast cancer.

PMID- 9586420
TI  - [Evidence-based medicine].

PMID- 9586421
TI  - [Epidemiology and chronorhythmicity of recurrences of attempted suicide].
AB  - The authors examine cases of attempted suicide admitted to Hospital of Foggia
      from 1 January 1990 to 31 December 1996. They describe characteristics of
      repeaters. A total of 611 episodes of attempted suicide regarding 552 different
      subjects were observed during the study period. Women attempted suicide more than
      men. No significant difference was observed for age and repeaters between men and
      women; while women outnumbered men in cases of single episode. Attempted suicide
      showed a circadian rhythm for both in first-event cases and repeaters; against,
      circaseptan and circannual periodicity were not present in both groups. Women had
      a greatest risk of an other repetition after a free period from events, in fact
      the time between the first and the latest episode was greater for women than for
      men. Commonly, the repeaters attempted at suicide again making use of the same
      method used for the first episode.

PMID- 9586422
TI  - Dopaminergic modulation of hexarelin-induced GH and PRL secretion in
      hyperprolactinemia.
AB  - Hexarelin (Hex), a synthetic GH-releasing peptide, has recently been found to
      possess a weak PRL-releasing effect in normals. The aims of this study were to
      investigate the effect of Hex on GH and PRL secretion in 10 hyperprolactinemic
      women (HPRL) and 7 controls (C). All subjects underwent stimulus testing with
      placebo, bromocriptine (Br) (2.5 mg po at time -60), Hex (2 micrograms/kg/bw
      i.v.), and Br plus Hex. During placebo, HPRL showed a higher (p < 0.01) PRL area
      under curve (AUC) than C. Br significantly (p < 0.01) reduced PRL AUC both in
      HPRL and in C. Hex was able to induce a slight but significant (p < 0.05) PRL
      release in both groups. PRL response to Hex was abolished (p < 0.01 vs Hex) by Br
      priming in HPRL, while it was only blunted (p < 0.05 vs Hex) in C. Br induced a
      significant (p < 0.01) GH increase in both groups. However, GH AUC after Br was
      significantly higher (p < 0.01) in C than HPRL. Hex induced a significant (p <
      0.01) GH release both in HPRL and in C. Br priming did not modify GH response to
      Hex in HPRL while it slightly (p < 0.05) increased GH response to Hex in C,
      suggesting that neuroendocrine modifications present in HPRL might, per se, be
      able to impair GH response to Br plus Hex, thus giving rise to receptor
      competition. Hex had a weak PRL-releasing effect in both groups studied, this was
      only blunted by Br priming in C but was abolished in HPRL, suggesting that
      oversensitivity to DA-ergic agents present in HPRL could be able to antagonize
      completely Hex action.

PMID- 9586423
TI  - [Nedocromil sodium is effective in the treatment of mild and moderate allergic
      asthma caused by Dermatophagoides pteronyssinus].
AB  - We have evaluated the efficacy of nedocromil sodium in 38 patients (18 males and
      20 females, mean age 37.2 yrs) suffering from mild or moderate allergic asthma
      due to Dermatophagoides pteronissinus. Nedocromil sodium was given twice a day at
      the dosage of 4 mg each time for two months. On a daily diary card patients had
      to record the severity and the number of asthmatic attacks, the usage of
      bronchodilators and the values of peak respiratory flow measured in 1/min in the
      morning and at night. The improvement of the parameters considered was
      statistically significant, and no side effects have been observed. Nedocromil
      sodium is therefore an efficacious and safe drug in the treatment of mild and
      moderate asthma induced by Dermatophagoides pteronyssinus.

PMID- 9586424
TI  - [Post-infantile giant cell hepatitis. Clinical and histological response to
      immunosuppressive therapy].
AB  - Giant cell transformation of hepatocytes combined with variable degrees of
      hepatocyte necrosis and liver fibrosis is distinctly uncommon in adults. In this
      age group it has most often been associated with autoimmunity, drug reaction and
      viral infection. Prognosis is considered quite severe ranging from mild fibrosis
      to established cirrhosis. We report a case of giant cell hepatitis that occurred
      in a 30 yrs old man, who had been taking ticlopidine for 3 years. The causative
      role of the drug is uncertain because aminotransferase did not fall after
      withdrawal. The patient fulfilled most of the criteria for a diagnosis of
      autoimmune hepatitis and was treated accordingly with prednisolone and
      azathioprine. Immunosuppressive therapy led to a clinical, biochemical and
      histological response.

PMID- 9586425
TI  - [Pertussis in the adult].

PMID- 9586426
TI  - [Endocarditis caused by Eubacterium spp].

PMID- 9586427
TI  - [Ethics committee of the Floriani Foundation and the Italian Society for
      Palliative Treatment on "Di Bella's treatment"].

PMID- 9586428
TI  - [Apparatus of control of the cell cycle].

PMID- 9586429
TI  - [Cryptogenic fibrosing alveolitis. Current aspects].

PMID- 9586430
TI  - [Evidence-based medicine. 1. The transfer of research results to clinical
      practice. The Italian Group for Evidence-Based Medicine-GIMBE].
AB  - Evidence-based Medicine, born officially in November 1992, during last five years
      is grown everywhere, showing its power to influence virtually all aspects of
      health care: clinical practice, medical education, patient information and health
      policy. Because of the raising interest also in Italy for the new paradigm of
      clinical practice, "Recently Progress in Medicina" launches a series of articles
      with the aim of giving to physicians tools and skills for searching, critically
      appraising and implementing in their own decisions the best results of clinical
      research. For a better explanation of practical aspects of Evidence-based
      Medicine, the first article discusses about several obstacles existing in
      transferring correctly and timely the results of research into clinical practice,
      and about the potential role of Evidence-based Medicine in the evolution of the
      medical art and the health systems of the third millennium.

PMID- 9586431
TI  - [Spondyloarthropathies: diagnostic criteria, classification and prognosis].

PMID- 9586432
TI  - [Silent axial arthropathy in inflammatory bowel disease. Clinical, radiological
      and genetic characteristics].
AB  - OBJECTIVES: To evaluate the prevalence, clinical and radiological
      characteristics, association with HLA B27 in a subgroup of patients with
      inflammatory bowel disease (IBD) and subclinical sacroileitis. The sensitivity of
      the diagnostic criteria for spondyloarthropathy in this group of patients is
      evaluated. MATERIALS AND METHODS: All patients with inflammatory bowel disease
      attending an outpatient gastroenterology unit from January 1994 to June 1994 were
      recruited. A total of 62 patients with IBD and without clinical evidence of axial
      involvement were included in the study. The demographic, clinical, and
      radiological characteristics were collected. The radiological examination
      included PA and lateral views for the dorso-lumbar, and three views (Ferguson,
      right and left oblique views) for the sacroiliac joints. Films were interpreted
      by three independent readers. The HLA B27 allele distribution was analyzed in the
      62 patients and in 80 healthy controls. The modified New York criteria, Amor
      criteria, and European Spondyloarthropathy Study Group criteria were evaluated.
      Patients were prospectively followed for two years with the same initial
      protocol. The statistical management of data was performed with the information
      program SPSS/PC. RESULTS: Fifteen cases of silent sacroileitis were detected, and
      most of them were grade 2 unilateral sacroileitis. There was no correlation
      between sacroileitis and IBP type, extradigestive symptoms, disease duration,
      sex, or peripheral arthritis. The frequency of HLA B27 in the sacroileitis group
      was 20% (p < 0.05). During the two-year follow-up period none of these cases has
      changed from diagnostic category. The sensitivity of diagnostic the criteria for
      spondyloarthropathy was low in these patients (40%-53%). CONCLUSIONS: A high
      frequency of asymptomatic sacroileitis in patients with IBD was detected. We
      propose the term Silent Axial Arthropathy to define this category of patients
      and, as with other authors, we consider this is a third form of rheumatic
      syndrome in IBD, different from the classical forms of peripheral arthritis and
      ankylosing spondylitis.

PMID- 9586433
TI  - [Pleural fluid to serum cholinesterase ratio to discriminate between transudates
      and exudates: reevaluation in 177 patients].
AB  - BACKGROUND AND OBJECTIVES: In a previous study we concluded that the pleural
      fluid/serum (PF/S) ratio of cholinesterase was the most useful parameter to
      discriminate between exudates and transudates. The objective of the present study
      was to confirm these findings in a prospective series of patients with pleural
      effusion. MATERIAL AND METHODS: A total of 177 patients, consecutively studied at
      two institutions, with the diagnosis of pleural effusion were included in this
      study. Thirty-six (20.3%) effusion were transudates and 141 (79.7%) exudates; of
      these, 73 and 68 were of malignant and benign origin, respectively. Both PF/S
      cholinesterase and Light's criteria were compared. RESULTS: The PF/S
      cholinesterase ratio incorrectly classified 12 pleural effusions (6.8%). These
      included 7 out the 36 transudates (19.4%) and 5 out of the 141 exudates (3.5%),
      the latter of malignant etiology. Following Light's criteria, four (2.2%)
      exudates were misclassified, all of them transudates. The higher accuracy of
      Light's criteria was statistically significant (p = 0.04). CONCLUSIONS: In this
      series of patients, Light's criteria were more accurate than PF/S cholinesterase
      ratio to discriminate between transudates and exudates. From these results, the
      use of the PE/S cholinesterase ratio parameters is no longer recommended.

PMID- 9586434
TI  - [Acute pancreatitis and infection with the human immunodeficiency virus].
AB  - BACKGROUND: Retrospective study of the etiology and evolution of 40 episodes of
      acute pancreatitis in 28 patients infected with the human immunodeficiency virus
      (HIV). RESULTS: AIDS criteria were met by 89.3% of patients. The likely etiology
      was an opportunist infection in 32.5% of episodes, drug use in 22.5%, and biliary
      lithiasis in 5%. AP secondary to AIDS-associated cholangitis occurred in 35.7% of
      episodes. Sixty percent of episodes were severe in nature. The mortality rate
      reached 30%. CONCLUSIONS: AP in HIV infected patients: a) is more frequent in the
      advanced stages of disease; b) opportunistic infections and drugs are the most
      frequent causes in our environment; c) in a third of patients it is probably
      secondary to AIDS associated cholangitis; d) biliary lithiasis seems to be less
      common than in the general population, and e) it is associated with a high
      severity and mortality.

PMID- 9586435
TI  - [Radiotherapy of localized cancer of the prostate: current status and new
      strategies].
AB  - Radiation therapy is a well established modality for the management of prostate
      cancer and the reported results are comparable to those obtained with radical
      prostatectomy. After the introduction of prostate specific antigen (PSA)
      determination, when results are analyzed on the basis of strict biochemical
      criteria, it is clearly evident that total and permanent eradication of the
      localized prostate cancer is obtained less frequently than what was thought in
      the las few decades. Although there are currently only a few series with radical
      radiation therapy with long results and with complete PSA determination during
      follow-up, disease free survival (DFS) for T1b-T2 Nx is approximately 65% at 4-5
      years, whereas for T1-2 NO DFS at 9-10 years is maintained between 67% and 83%.
      New therapeutic strategies leading to improvement in the locoregional control are
      discussed, including dose escalation programs in the setting of new technologies
      of three-dimensional conforma radiation therapy, and neoadjuvant androgenic
      blockade.

PMID- 9586436
TI  - [Obstructive colitis: analysis of 7 patients].
AB  - The term "obstructive colitis" is defined by the presence of ulcero-inflammatory
      lesions in a colonic area proximal to a potentially obstructive lesion. Seven
      cases retrospectively identified during a 5-year period are here reported. They
      illustrate the clinico-pathological spectrum of this entity. Most patients were
      women, with a mean age of 66 years and with history of chronic underlying disease
      (diabetes mellitus and arterial hypertension). Abdominal distension and pain, as
      well as acute constipation were the main clinical symptoms. An adenocarcinoma
      predominantly located at the rectosigmoidal region accounted for the obstructive
      nature in 100% of cases. Macroscopically the colitis area was moderately dilated
      and there were single or confluent ulcers in the luminal surface.
      Characteristically, there was always a transitional preserved area between the
      obstruction and the colitis area. Microscopically, the mucosa was totally
      replaced by a granulation tissue with a relevant inflammatory infiltrate
      involving up to the muscularis propria. The cytometric study revealed and
      increase in the cell cycle (S-phase) and proliferation index, at the level of the
      obstructive lesion, with marked aneuploidy in cases with advanced neoplastic
      invasion. The role of mural hypoperfusion with localized ischemia in the
      pathogenesis is discussed. The similarities with other colonic inflammatory
      diseases are emphasized.

PMID- 9586437
TI  - [Thalassemia intermedia caused by interaction of IVS-1 1(G--A) mutation in the
      beta-globin gene and heterozygotic triplication in the alpha-globin gene].
AB  - Thalassemia intermedia is a clinical entity characterized by moderate, non
      transfusional anemia and hepatosplenomegaly. This phenotype can result from
      different genetic combinations and is sometimes present in patients with only one
      parent showing the thalasemia minor phenotype. We report here a family with seven
      members with the thalassemia beta trait, four of them with thalasemia minor and
      the other three with thalassemia intermedia. The genetic study of patients with
      thalassemia intermedia revealed the presence of the mutation IVS-1 1(G-->A) in
      the beta-globin gene and the heterozygous triplication of the alpha-globin gene,
      an uncommon association in Spain. The interaction of a mutation in the beta
      globin gene with triplication of the alpha-globin gene should be considered in
      the diagnosis and genetic counselling in those patients with thalassemia
      intermedia and one normal parent.

PMID- 9586438
TI  - [Adduction spastic dysphonia: clinical and treatment].
AB  - Adduction spastic dystonia (SD) is currently considered a focal dystonia
      involving laryngeal muscles. SD is one of the most poorly known focal dystonias.
      We reviewed our experience with twentynine patients with adduction SD and
      compared the clinical and epidemiologic variables with the other focal dystonias
      studied at our institution in the last five years (132 patients). Mean age of
      patients (47.2 +/- 13 years), sex, clinical course in years (5.7 +/- 5) and
      presence of circadian fluctuations did not differ significantly from those
      observed in patients with other focal dystonias. Likewise, there were no
      significant differences regarding the presence of a family history of dystonia,
      essential tremor, or stuttering. Our results confirm the similarity of the
      clinical and epidemiologic data of SD with the other focal dystonias. All
      patients with SD were treated with a local injection of botulinum toxin. A total
      of 108 treatments were performed, 41 with a visually guided transoral technique
      and 67 with a percutaneous technique. The transoral technique was effective in
      all cases (41/41) but not all treatments with the percutaneous technique were
      effective (53/67). Three patients required the shift to the transoral procedure
      to achieve enough symptomatic alleviation.

PMID- 9586439
TI  - [Mild cognitive impairement in the elderly].

PMID- 9586440
TI  - [Prions and transmissible spongiform encephalopathies: a justifiable alarm?].

PMID- 9586441
TI  - [Palpable abdominal mass].

PMID- 9586442
TI  - [27 year-old woman with symmetrical abdominal neoplasms].

PMID- 9586443
TI  - [Woman with non-insulin dependent diabetes mellitus, brachydactyly, hypocalcemia
      and arterial hypertension].

PMID- 9586444
TI  - [Fever and muscular pain in a 34 year-old man].

PMID- 9586445
TI  - [Replacement therapy with nicotine. Practical aspects].

PMID- 9586446
TI  - [Animal bites. Study of 606 cases].

PMID- 9586447
TI  - [Epidemiology of the osteoporotic hip fracture].

PMID- 9586448
TI  - [Wegener granulomatosis: localized variant].

PMID- 9586449
TI  - [The role of plasmapheresis in the POEMS syndrome. Case report].

PMID- 9586450
TI  - Histological evaluation of peri-implant bone at implants subjected to occlusal
      overload or plaque accumulation.
AB  - Breakdown of bone around oral implants following occlusal overload or plaque
      accumulation was evaluated in monkeys. 5 screw-type implants of pure titanium
      (Astra Tech) were inserted in the mandible of 4 monkeys (Macaca Fascicularis). 6
      months after insertion of the implants a fixed partial prosthesis was mounted on
      the 2 implants in 1 of the lateral segments. The prosthesis was in supra-occlusal
      contact with an antagonizing splint and caused a lateral directed excessive
      occlusal load (overload). Implants retaining the prosthesis were brushed 1 x week
      and subgingival cleaning was performed 1 x month. The remaining implants were
      never cleaned and, additionally, a cotton cord was placed around the abutments of
      these implants to promote plaque accumulation. 6 out of 8 implants with occlusal
      overload became loose. 2 of these were lost, whereas the remaining 4 were
      retained in the jaws. After 18 months of occlusal load or plaque accumulation,
      the monkeys were sacrificed. Tissue blocks with the implants were infiltrated and
      embedded in acrylic resin. Approximately 50 microns thick sections of the
      implants and surrounding tissues were made. All implants with plaque accumulation
      were osseointegrated, but exhibited an average histologic marginal bone loss of
      2.4 mm (range: 0.8-4.0 mm). Of the 6 implants with occlusal overload available
      for histologic analysis, 2 implants in 1 monkey had lost osseointegration
      completely and 2 other implants were osseointegrated in the apical part only,
      whereas the remaining 2 were still osseointegrated but exhibited a bone loss of
      1.8-1.9 mm.

PMID- 9586451
TI  - Guided bone regeneration in dental implant treatment using a bioabsorbable
      membrane.
AB  - The aim of this study was to evaluate an osteopromotive technique, using a
      bioabsorbable membrane, for its ability to restitute bone over buccal
      fenestration and dehiscence defects following fixture installation. 11 patients
      requiring dental implant treatment and exhibiting sufficient vertical height of
      the maxilla and compromised bucco-palatal dimensions, as determined clinically
      and radiographically, were included in the study. 17 Branemark titanium fixtures
      were placed with buccal defects which were augmented by a bioabsorbable membrane,
      Resolut. No complications were observed post-operatively. At 6-8 months, abutment
      connection was performed, and clinical evaluation of the healed defect area was
      made. The number of exposed buccal threads at fixture installation (median 8;
      range 2-19), and abutment connection (median 0; range 0-5), respectively, was
      compared. Out of the 17 fixtures; 14 exhibited complete coverage with bone,
      whereas 3 showed some remaining threads. A small punch biopsy taken at abutment
      connection in an area where the membrane had been placed showed a combination of
      dense connective tissue and bone. Radiographic evaluation of the marginal
      periimplant bone level is in progress and results to date show a median bone loss
      of 1.2 mm after a loading period of 4-6 months. Results show that fixture
      dehiscence and fenestrations, augmented with this bioabsorbable membrane,
      demonstrate a highly significant amount of new bone formation.

PMID- 9586452
TI  - Influence of bone quality on the stress distribution. An in vitro experiment.
AB  - Adequate bone quality and stress distribution to the bone are of decisive
      importance for implant success. The purpose of this in vitro study was to
      investigate the influence of bone quality on the stress distribution using 2
      implant-bone mimicking models, simulating compact and cancellous bone quality.
      The resin model was made of an acrylic resin only simulating compact bone
      quality. The hybrid model was made of 2 kinds of materials, acrylic resin covered
      with a 1-mm layer of urethane to simulate cancellous bone quality. An implant was
      embedded in each model, and the abutment and suprastructures were connected to
      the implant. A strain gauge was placed perpendicular to the implant on the
      surface of the model and a small accelerometer was attached to the abutment. When
      an impact load was applied to the suprastructure, both strain and acceleration
      were measured. Both abutment acceleration and surface strain in the hybrid model
      decreased rapidly as time progressed when compared to the resin model. Abutment
      accelerations in the resin model were significantly lower than those in the
      hybrid model. In the hybrid model, the strain increased as the loading site was
      moved closer to the strain gauge. The influence of loading sites on strain in the
      resin model was greater than in the hybrid model. Therefore, the occlusal stress
      was distributed more widely in the hybrid model than in the resin model. This may
      indicate that occlusal stress in compact bone may have a tendency to concentrate
      in particular regions.

PMID- 9586453
TI  - Bacterial penetration through Resolut resorbable membrane in vitro. An
      histological and scanning electron microscopic study.
AB  - The aim of this study was to evaluate the characteristics of resorption and the
      pattern of bacterial collonisation of polyglycolic and polylactic resorbable
      membranes under controlled experimental conditions. A removable cobalt-chromium
      device was applied to the lower jaw of 5 students for a period of 4 weeks. 8
      composite resin chambers were glued to the device, 4 on each side of the mouth. A
      small piece of PLA/PGA membrane separated the composite chambers into 2 parts.
      The subjects wore the devices 24 h a day, except for the time necessary for oral
      hygiene procedures, during which time, the structure was submerged in a 0.2%
      chlorexidine solution. Every week, 2 of the chambers were removed; one was
      processed for scanning electron microscopy, to be observed both on the external
      and internal surface, and the other one for light microscopy examination. Both
      the electron microscopic and histologic observations showed a progressive
      increase in the plaque layer on the external surface of the membrane during the
      period of observation. The light microscopy showed an early invasion of the
      membrane, starting about 1 week after the exposure. On all the 3- and 4-week
      specimens, a complete bacterial invasion over the whole thickness of the membrane
      was visible. After 3 weeks of plaque accumulation, bacterial colonisation of the
      inner portion of the membrane was detectable in all the specimens. At 3-weeks, we
      observed in the light microscopy group in 4 out of 5 specimens, a large reduction
      of the thickness of the material and small voids in the membrane structure. In 1
      specimen, the membrane was no more detectable. Only in 5 specimens of the 4-week
      group was the membrane still recognizable, though reduced to fragments. In
      conclusion, once exposed to the oral cavity, the PLA/PGA membranes start to
      resorb in the early stages: this process concludes itself between the 3rd and 4th
      weeks of exposure. However, the particular conditions of the experimental design
      nevertheless classify this study as an in vitro, more than as an in vivo
      experimentation.

PMID- 9586454
TI  - Markers of inflammation in crevicular fluid from peri-implant mucosa surrounding
      single crystal sapphire implants.
AB  - The 19 patients included in this study had all been successfully treated for
      total or partial edentulism with single crystal sapphire implants as retention
      for overdentures or fixed bridges. As there is a need for more reliable non
      invasive parameters for detecting changes surrounding endosseous implants, the
      aim of this study was to assess the content and the activity of neutrophils in
      crevicular fluid samples from 3 categories of sites: (1) crevices around implants
      from edentulous patients (2) crevices around implants in partially edentulous
      patients, and (3) crevices surrounding teeth. Fluid samples were taken with paper
      strips from 9 partially edentulous and 10 edentulous patients and the volume
      measured with a Periotron 6000. Elastase activity was measured as a marker of
      neutrophil activity and lactoferrin concentration as a marker of the number of
      neutrophils. Elastase activity per microliter and lactoferrin concentration was,
      despite similar clinical and radiographic signs, significantly higher in samples
      from crevices surrounding teeth and implants in the partially edentulous patients
      compared to samples from crevices around implants in the totally edentulous
      patients. There were no differences between teeth and implants in partially
      edentulous patients. The increased elastase activity and lactoferrin
      concentration indicates a higher neutrophil activity in patients with remaining
      teeth.

PMID- 9586455
TI  - Healing at implants with and without primary bone contact. An experimental study
      in dogs.
AB  - The aim of the present investigation in the dog was to study: (i) if it was
      possible by the use of EREt to predictably expand the compromised alveolar ridge;
      (ii) if proper osseointegration also occurred at sites where the implant
      following installation was devoid of direct bone contact. 5 beagle dogs, about 1
      year old, were included in the study. During a preparatory period, the mandibular
      premolars were extracted and the ridge in the edentulous regions markedly
      reduced. After 3 months of healing, ridge expansion surgery was performed. A
      partial thickness flap was raised on the buccal and lingual surfaces for the soft
      tissue preparation. The buccal part of the ridge was mobilised and the bone plate
      with its periosteum displaced in the buccal direction. In each quadrant, 2
      fixture sites were prepared in the mandibular bone apical of the displaced bone
      plate. 2 unthreaded titanium plasma sprayed fixtures were installed in such a way
      that the coronal border of the fixture was flush with the level of the lingual
      and buccal bone plate. The "internal" distance between the mobile buccal and the
      non-mobile lingual bone plates was identical to the diameter of the fixtures,
      i.e., 3.3 mm, while the distance between the mesial and distal borders of the 2
      implants and the mesial or distal bone was > 5 mm. In each quadrant, 1 additional
      fixture was installed in the non- reduced mesial part of the alveolar ridge
      (control site). 3 months after fixture installation, abutment connection was
      performed. Following abutment connection, a plaque control program was initiated
      and maintained for 4 months, at which time, the dogs were re-examined and
      biopsies obtained for histological examination. It was observed that bone
      regeneration and osseointegration may occur to titanium fixtures placed in
      surgically-created bone defects. The amount of bone that was in intimate contact
      with the fixture surface was similar in test and control sites. In addition, the
      periimplant mucosa at test and control implants had similar dimensions and
      composition in terms of junctional epithelium and connective tissue.

PMID- 9586456
TI  - Implant-retained mandibular overdentures with immediate loading. A retrospective
      multicenter study on 226 consecutive cases.
AB  - A multicenter retrospective study has been conducted on 226 patients
      necessitating an implant-supported overdenture in the lower jaw. The patients
      were provided with 904 osseointegrated implants inserted in the interforaminal
      area of the mental symphisis (4 implants per patient). 4 titanium implant systems
      were used: TPS and ITI screw implants (Straumann Institute, Waldenburg,
      Switzerland); Ha-Ti screw implants (Mathys Dental Implants, Bettlach,
      Switzerland); NLS screw implants (Friatec, Mannheim, Germany). Immediately after
      implant placement, a U-shaped gold bar was fabricated and implants were
      immediately loaded with an implant-retained overdenture. Out of 226 patients
      treated, 194 were followed from a minimum of 2 years to a maximum of 13 years,
      with a mean follow-up of 6.4 years, whereas 32 patients dropped out during follow
      up. The overall failure rate of implants was 3.1% (24/776 implants), whereas the
      failure rate of bars was 1.5% (3/194 bars). Results from this study showed that
      the success rate of immediately loaded implants is similar to that obtained in
      the case of delayed loading, after osseointegration has taken place. In contrast,
      this method shortens dental rehabilitation times with relevant satisfaction for
      patients.

PMID- 9586457
TI  - Long-term evaluation of single crystal sapphire implants as abutments in fixed
      prosthodontics.
AB  - 49 patients participated in a prospective study of treatment of total or partial
      edentulism with fixed prosthodontics supported by Bioceram sapphire implants. 15
      patients were treated for maxillary or mandibular edentulism, and 7 for a missing
      maxillary anterior tooth. The remaining 27 patients, with Applegate-Kennedy Class
      I-IV residual dentitions, were treated with fixed bridges supported by free
      standing implants, or bridges supported by teeth and implants. Implant success,
      prosthesis stability, radiographic marginal bone level as well as parameters for
      peri-implant health were evaluated. The study began in 1982, and clinical
      treatment of the last patients was completed in 1988, i.e., a follow-up period
      ranging from 7 to 13 years. Of the patients treated for total mandibular
      edentulism, one implant fractured after 6 years in situ. The bone implant score
      (BIS) values for those implants were at the time for the bridge cementation 63.5
      +/- 1.4 and at 1, 2, 3 and 5 year follow-ups 62.1 +/- 1.4, 61.9 +/- 1.5, 61.5 +/-
      1.6, and 60.95 +/- 1.3, respectively. The success rate was 100%, 100% and 97.7%
      for the mandible at 3, 5 and 10 years, respectively. Of the 7 edentulous patients
      treated with maxillary fixed bridges, 6 implants in 1 patient had to be removed
      after 1 year in service. Another 2 patients lost all their implants, 6 each,
      after 36 months. 6 implants in the 4th patient did not fulfil the criteria for
      success and were rated as failures at the four year follow-up. The success rate
      was thus 58.1%, 44.2% and 44.2% for the maxilla at 3, 5 and 10 year follow-ups,
      respectively. Of the 7 patients in whom single missing teeth were replaced, 1
      implant in the premolar region was lost during the 1st year post-operatively, but
      no other complications or changes in BIS were observed. Of the 27 patients
      treated for partial edentulism (56 implants total) 1 implant, of a 4-unit free
      standing maxillary bridge fractured after 6 years and was later replaced. There
      were no statistically significant differences in BIS changes for the implants
      when used as abutments for partial maxillary or mandibular edentulism. The
      cumulative success rates for the implants in the partially maxilla were 96.3,
      92.6 and 92.6 at the 3, 5 and 10 years respectively and 100% in the mandible over
      the whole period.

PMID- 9586458
TI  - Stability of hydroxyapatite-coatings on titanium oral implants (IMZ). 2 retrieved
      cases.
AB  - 2 hydroxyapatite(HA)-coated titanium oral implants (IMZ) were retrieved from 2
      patients after more than three years in clinical function. One implant (case I)
      was removed because of extensive bone resorption and loss of integration, and the
      other (case II) was retrieved due to fracture of the abutment in sprit of
      clinical rigidity. The implants and the surrounding soft (case I) and hard (case
      II) tissues were examined histologically and by scanning electron microscopy
      (SEM). In case I, the HA-coating was almost degraded, as SEM revealed a resulted
      rough titanium surface. Histology showed HA particles and inflammation were seen
      near the implant. In Case II, the HA-coating seemed to be intact and bonded to
      bone, but scattered HA particles, embedded in bone at a distance from the implant
      were also observed. The results indicate that HA-coatings may come loose during
      clinical function. The long-term stability of HA-coatings and the clinical
      indications for HA-coated implants warrant further study.

PMID- 9586459
TI  - A survey on dental care and oral implantology in Beijing, China.
AB  - In this article, we present a survey on dental care and oral implantology in
      Beijing, China. The Chinese population comprises 1.2 billion or about 20% of the
      world's population. This survey shows: (i) there is a well-developed dental
      system in China, mostly operated by the Chinese government; (ii) in Beijing,
      there are 1328 dentists and oral surgeons and 515 special dental nurses working
      in dental departments of hospitals; (iii) about 2 million new patients visit the
      dentist every year; (iv) oral implantology is a new technology for the Chinese
      dentist and oral surgeon, as shown by the finding that in 1992, only 384 persons
      were treated with oral implants in a few hospitals in Beijing; however, most
      hospitals are interested in performing oral implantology in the near future; (v)
      imported implants are too expensive for Chinese patients, and therefore good
      qualified domestic implants and cheaper imported implants have a great market
      potential.

PMID- 9586460
TI  - Long-term evaluation of non-submerged ITI implants. Part 1: 8-year life table
      analysis of a prospective multi-center study with 2359 implants.
AB  - In the present multi-center study, non-submerged ITI implants were prospectively
      followed to evaluate their long-term prognosis in fully and partially edentulous
      patients. In a total of 1003 patients, 2359 implants were consecutively inserted.
      Following a healing period of 3-6 months, the successfully integrated implants
      were restored with 393 removable and 758 fixed restorations. Subsequently, all
      consecutive implants were documented annually up to 8 years. At each examination,
      the clinical status of all implants was evaluated according to predefined
      criteria of success. Therefore, the data base allowed the evaluation of 8-year
      cumulative survival and success rates for 2359 implants. In addition, cumulative
      success rates were calculated for implant subgroups divided per implant type,
      implant length, and implant location. Furthermore, the actual 5-year survival and
      success rates could be determined for 488 implants. During the healing period, 13
      implants did not successfully integrate, whereas 2346 implants fulfilled the
      predefined criteria of success. This corresponds with an early failure rate of
      0.55%. During follow-up, 19 implants were classified as failures due to several
      reasons. In addition, 17 implants (approximately 0.8%) demonstrated at the last
      annual examination a suppurative periimplant infection. Including 127 drop out
      implants (= 5.4% drop out rate) into the calculation, the 8-year cumulative
      survival and success rates resulted in 96.7% and 93.3%, respectively. The
      analysis of implant subgroups showed slightly more favorable cumulative success
      rates for screw type implants (> 95%) compared to hollow-cylinder implants
      (91.3%), and clearly better success rates for mandibular implants (approximately
      95%) when compared to maxillary implants (approximately 87%). The actual 5-year
      survival and success rates of 488 implants with 98.2% and 97.3%, respectively,
      were slightly better than the estimated 5-year cumulative survival and success
      rates of 2359 implants indicating that the applied life table analysis is a
      reliable statistical method to evaluate the long-term prognosis of dental
      implants. It can be concluded that non-submerged ITI implants maintain success
      rates well above 90% in different clinical centers for observation periods up to
      8 years.

PMID- 9586461
TI  - A prospective study of Astra single tooth implants.
AB  - A new design of single tooth implant (AstraTech, Molndal Sweden) featuring a
      microthreaded conical neck and TiO blast surface was evaluated clinically and
      radiographically after 2 years in function. Fifteen patients (age range 16 to 48)
      with missing maxillary anterior teeth (6 central incisors, 8 laterals, 1
      bicuspid) had 4, 13 mm and 11, 15 mm implants placed under local anaesthesia and
      left for a period of 6 months before exposure and abutment connection/crown
      fabrication. All patients were seen at 4 to 6 monthly intervals for hygienist
      maintenance. Radiographs using Rinn holders and a long cone technique were taken
      at the crown insertion and after 1 year (14 subjects) and 2 years (12 subjects).
      All implants were successfully integrated at stage 2, and no implants have been
      lost. The internal conical seal design of the abutment/implant interface
      facilitated connection and there were no cases of abutment screw loosening. No
      soft tissue problems were observed, and the gingival morphology/health was well
      maintained. One crown was recemented after 18 months in function, and 1 crown was
      replaced because of a fracture to the porcelain incisal edge. At crown insertion,
      the mean bone level was 0.46 to 0.48 mm apical to the top of the implant and
      there were no statistically significant changes in the bone level over the 2
      years of the study. In conclusion, the single tooth Astra implants were highly
      successful and bone changes within the first 2 years of function were comparable
      with other systems reporting high long-term success rates.

PMID- 9586462
TI  - Implant therapy in periodontally compromised patients.
AB  - The present study evaluate the outcome of implant therapy in periodontally
      compromised patients in need of additional functional tooth support. A total of
      31 Astra implants and 93 ITI Dental Implant System implants were inserted in 19
      and 56 patients, respectively. The length of the implants varied between 8 and 14
      mm, with 45% being 8 mm and 21% being 11 mm or more. Most implants were placed in
      the maxilla, predominantly in the premolar region, while less than 25% were
      placed in the mandible. The observation period ranged between 12 and 40 months
      for Astra implants and between 3 and 84 months for ITI implants. At annual recall
      visits, 4 sites on all implants were assessed for presence of plaque, bleeding on
      probing, probing depth, and radiographic assessment of bone loss was performed. A
      total of 3 implants, all ITI implants, failed, yielding a 3-year survival rate of
      95-100%, depending on type of implant. After 3 years, 76-86% of all implants
      remained free from radiographic bone loss > or = 1.5 mm. After 5 years, 55% of
      the ITI implants remained free from such bone loss. These results indicate that
      periodontally compromised patients, who have experienced a considerable loss of
      alveolar bony support, can be successfully treated with implants.

PMID- 9586463
TI  - Influence of different parameters on bone heating and drilling time in
      implantology.
AB  - The influence of various parameters on bone heating during drilling and drilling
      time was studied in vitro in a bovine cortical femur model. Drilling using a
      standard, a surgical or a laboratory motor unit did not affect bone temperature
      elevation. For a given speed, low 1/40 reduction contra-angle was more effective
      in moderating temperature elevation when compared to 1/10 reduction; but drilling
      time in this case (1/40) had to be doubled. Enhancing the drilling load from 0.8
      kg to 2 kg had little effect on temperature elevation at 400 rpm and 800 rpm (< 3
      degrees C). Drilling time drastically decreased and was inversely proportional to
      the square of the load. Predrilling did not affect temperature elevation, but
      decreased drilling time. From 400 rpm to 10,000 rpm, temperature elevation was
      positively correlated with drilling speed. It further decreased up to 24,000 rpm
      and then was constant up to 40,000 rpm. Drilling time was proportionally reduced
      with increased rotation speed. Strikingly, heat was largely dissipated within 10
      s at high rotation speed. The use of a cryogenic spray at 24,000 rpm allowed the
      reduction of temperature elevation. Finally, protection from temperature
      elevation according to above parameters is suggested.

PMID- 9586464
TI  - The biological effect of natural bone mineral on bone neoformation on the rabbit
      skull.
AB  - The aim of this study was to evaluate the effect of deproteinized bovine bone
      graft material on new bone formation in a guided bone regeneration model system.
      In 20 rabbits, a periosteal skin flap was raised uncovering the calvaria. A form
      stable hemispherical dome made of poly-lactic acid (PLA) was placed onto the
      roughened calvaria. Prior to placement, the dome was either filled with
      peripheral blood alone (control group, 8 rabbits), or with blood and OsteoGraf/N
      300 (test group, 12 rabbits). The wound was closed for primary healing.
      Morphometric assessment of 1- and 2-month undecalcified histologic specimens
      revealed better tissue fill in the test domes at 1 month (test 99%, control 55%)
      (P < 0.05) and 2 months (t, 100%; c, 82%). The fraction of the new bone within
      the regenerated tissue was higher in the test specimens at 1 month (t, 22%; c,
      12%) (P < 0.05) and 2 months (t, 34%; c, 24%). The fraction of the entire space
      underneath the domes occupied by bone was higher in the test at 1 month, but
      higher in the controls at 2 months. The fraction of the bone substitute material
      in contact with bone increased from 1 month (34% +/- 14) to 2 months (45% +/- 5).
      The surface fraction of osteoblast layers was tendentially higher in the test at
      1 month but higher in the control specimens at 2 months. In both test and
      control, initially woven bone was formed which underwent subsequent remodeling.
      Cellular degradation of the deproteinized bone graft was frequently detected. It
      is concluded that deproteinized bovine bone mineral has osteoconductive
      properties and can initially accelerate new bone formation during guided bone
      regeneration by increased recruitment of osteoblasts.

PMID- 9586465
TI  - Influence of surface treatments developed for oral implants on the physical and
      biological properties of titanium. (I) Surface characterization.
AB  - We present an investigation of the physico-chemical surface properties of
      commercially pure titanium coverslips which were submitted to various treatments
      designed to optimize their topography in view of application in oral
      implantology. The surface microroughness, chemical composition and water
      wettability were analyzed on titanium coverslips prepared by mechanical
      polishing, acid attack in HCl/H2SO4, after mechanical polishing or sandblasting,
      and titanium plasma-spray. The chemical composition has been measured by Auger
      electron spectroscopy. The treatments have no major influence on the surface
      chemical composition and all the samples display a composition approaching that
      of TiO2 with minor amounts of carbon, sulfur, silicon and calcium as impurities.
      The roughness has been measured by scanning force microscopy on an area of 20
      microns x 20 microns on each sample. Polished titanium is smooth (peak-to-valley
      roughness 81 nm), whereas the acid-attacked surfaces exhibit a micro-roughness in
      the microns range (2100 nm for polished and acid attacked; 3600 nm for
      sandblasted and acid attacked) which is quite reproducible over large areas of
      the sample. The acid attacked samples present a subsurface layer which contains
      hydrogen below the native passivating oxide layer. Water wettability measurement
      shows that all surfaces are hydrophobic with a slightly higher contact angle for
      the acid attacked surfaces. The different treatments analyzed in this study
      essentially influence the surface roughness by preserving the chemical
      composition and the wettability properties of titanium native oxide surface
      layer.

PMID- 9586466
TI  - Influence of surface treatments developed for oral implants on the physical and
      biological properties of titanium. (II) Adsorption isotherms and biological
      activity of immobilized fibronectin.
AB  - The influence of titanium surface properties on in vitro adsorption isotherms of
      fibronectin, promotion of Staphylococcus aureus adhesion, and binding of a
      monoclonal antibody to the cell-binding domain of fibronectin was examined.
      Treatments producing different surface roughness were applied to a single side of
      commercially pure titanium coverslips, which was either mechanically polished
      (P), or polished and then acid attacked with H2SO4/HCl (PA), or sandblasted and
      then acid attacked (SLA), whereas the untreated side was blocked by an albumin
      coating layer. Incubation of the coverslips with concentrations of soluble 3H
      labelled fibronectin increasing from 1 to 16 micrograms/ml led to the saturation
      of all surfaces with immobilized protein from 4 to 16 micrograms/ml. Promotion of
      S. aureus adhesion by fibronectin adsorbed on all surfaces and binding of the
      monoclonal antibody to its cell-binding domain was to some extent proportional to
      the amount of immobilized protein but also showed some minor differences between
      surfaces. More important material-related differences were observed when
      fibronectin adsorption isotherms were expressed as a function of the effective,
      roughness-corrected surface area, yielding amounts of immobilized fibronectin on
      the rough PA and SLA titanium surfaces which were 50% lower than those adsorbed
      on either smooth P or polymethylmethacrylate coverslips used as controls. In
      conclusion, surface treatments increasing the surface roughness of titanium do
      not increase, but may partly decrease in vitro adsorption of fibronectin. Despite
      adsorbing different amounts of fibronectin, both rough and smooth titanium
      surfaces promote normal expression of 2 major functional domains of this protein.

PMID- 9586467
TI  - Resonance frequency measurements of implant stability in vivo. A cross-sectional
      and longitudinal study of resonance frequency measurements on implants in the
      edentulous and partially dentate maxilla.
AB  - The aim of this investigation was to evaluate the use of resonance frequency
      measurements in the clinical measurement of implant stability. Resonance
      frequency measurements are undertaken by measuring the response of a small
      transducer attached to an implant fixture or abutment. Two groups of patients
      were selected for study. Group A comprised 9 patients who had a total of 56
      implants placed. Resonance frequency measurements were made at fixture
      installation and repeated 8 months later at abutment connection. The resonance
      frequency of the implant/transducer system increased for 50 out of the 56
      implants from a mean value of 7473 Hz +/- 127 Hz (P < 0.05) to a mean of 7915 Hz
      +/- 112 Hz (P < 0.05). Two implants had failed to integrate and the resonance
      frequency of these had fallen. Group B comprised 9 patients who had been provided
      with fixed prostheses and had a total of 52 implants placed. They were examined 5
      years after fixture placement and the prostheses removed. All implants were
      judged clinically to be osseointegrated. The level of the marginal bone around
      each implant was calculated by measuring the number of exposed threads on
      intraoral periapical radiographs and added to the length of each abutment to give
      a value termed the effective implant length (EIL). Measurements indicated a
      correlation (R = -0.78, P < 0.01) between EIL and resonance frequency. The
      results support the hypothesis that the resonance frequency of an
      implant/transducer system is related to the height of the implant not surrounded
      by bone and the stability of the implant/tissue interface as determined by the
      absence of clinical mobility.

PMID- 9586468
TI  - The application of resonance frequency measurements to study the stability of
      titanium implants during healing in the rabbit tibia.
AB  - The aim of this investigation was to measure the resonance frequency of a number
      of implants placed in the rabbit tibia at insertion and at predetermined periods
      thereafter and to correlate the results with histomorphometric measurements made
      when the animals were sacrificed. Ten mature New Zealand White rabbits were used
      in the study. Two c.p. threaded titanium implants were placed in the right tibia
      of each animal. Resonance frequency measurements were made by screwing a small
      transducer onto a standard abutment mounted on each fixture. Measurements were
      repeated with the transducer oriented perpendicular and parallel to the long axis
      of the tibia for all proximal implants 14 and 28 days after placement and in 6
      implants additionally at 42, 56, 93, 122 and 168 days after which all animals
      were sacrificed. Histomorphometric analysis comprised 2 parts; measurement of
      bone-implant contact area and height. A significant increase in resonance
      frequency was observed after 14 (405 Hz, +/- 234 Hz) and 28 (658 Hz, +/- 332 Hz)
      days. The increase in resonance frequency levelled after approximately 40 days
      and little further change was observed. The variation in bone-implant contact
      area was relatively small (1.8-4.9 mm2) and the range of bone-implant contact
      heights was also narrow (-1.5 (-)+ 1.5 mm). Values for resonance frequencies
      plotted against contact area and height were grouped around 10 kHz. In
      conclusion, it was shown that resonance frequency measurements can be made at
      placement and during healing in vivo and changes may be related to the increase
      in stiffness of an implant in the surrounding tissues.

PMID- 9586469
TI  - The significance of angiogenesis in guided bone regeneration. A case report of a
      rabbit experiment.
AB  - A dome-shaped bioresorbable membrane was fixed to the wounded rabbit calvaria and
      filled with a bioresorbable fibre conglomerate. After 4 weeks, the histologic
      preparation revealed an intimate spatial and temporal correlation between newly
      formed blood vessels and de novo extraskeletal bone formation. These observations
      emphasize the significance of angiogenesis in guided bone generation.

PMID- 9586470
TI  - Elimination of bacteria on different implant surfaces through photosensitization
      and soft laser. An in vitro study.
AB  - Microbiologic examinations of implants have shown that certain microorganisms
      described as periodontal pathogens may have an influence on the development and
      the progression of peri-implant disease. This experimental study aimed to examine
      the bactericidal effect of irradiation with a soft laser on bacteria associated
      with peri-implantitis following exposure to a photosensitizing substance.
      Platelets made of commercially pure titanium, either with a machined surface or
      with a hydroxyapatite or plasma-flame-sprayed surface or with a corundum-blasted
      and etched surface, were incubated with a pure suspension of Actinobacillus
      actinomycetemcomitans or Porphyromonas gingivalis or Prevotella intermedia. The
      surfaces were then treated with a toluidine blue solution and irradiated with a
      diode soft laser with a wave length of 905 nm for 1 min. None of the smears
      obtained from the thus treated surfaces showed bacterial growth, whereas the
      smears obtained from surfaces that had been subjected to only one type of
      treatment showed unchanged growth of every target organism tested (P < 0.0006).
      Electron microscopic inspection of the thus treated platelets revealed that
      combined dye/laser treatment resulted in the destruction of bacterial cells. The
      present in vitro results indicate that lethal photosensitization may be of use
      for treatment of peri-implantitis.

PMID- 9586471
TI  - Clinical probing and radiographic assessment in relation to the histologic bone
      level at oral implants in monkeys.
AB  - Clinical probing level and radiographic bone level were compared to histologic
      bone level around screw type oral implants in 4 monkeys (Macaca Fascicularis).
      Two implants in each monkey retained a fixed partial prosthesis in supra-occlusal
      contact with an antagonizing splint. These implants were brushed 1 x a week and
      subgingival cleaning was performed 1 x a month. Unloaded implants in the same
      monkeys were never cleaned and, additionally, a cotton cord was placed around
      these to promote plaque accumulation. After 18 months, intraoral radiographs of
      the implants were obtained and probing levels were recorded with a metal probe
      using a standardized force of 0.2 N (Vivacare TPS Probe) and again using a
      moderate, unstandardized pressure. Immediately afterwards the animals were
      sacrificed. Sections, approximately 50 microns thick, of the implants and
      surrounding tissue were cut. The average probing levels with unstandardized
      pressure were 1.1 mm and 3.9 mm coronal to the histologic bone levels for
      implants with plaque accumulation or excessive occlusal load, respectively. With
      standardized probing force, the difference between the probing levels and
      histologic bone levels were even larger. The radiographic bone levels were on
      average only 0.5 mm and 0.1 mm short of the histologic bone levels for the two
      groups of implants. Only the radiographic bone level revealed a statistically
      significant correlation with the histologic assessment.

PMID- 9586472
TI  - Patient's opinion and treatment outcome of fixed rehabilitation on Branemark
      implants. A 3-year follow-up study in private dental practices.
AB  - In this study, patient opinion on oral rehabilitation by means of Branemark
      implants was investigated. All patients were referred to a periodontal clinic for
      implant installation and treated by one and the same operator. Prosthetic
      restorations were performed by dentists, who had no previous experience with
      prostheses on implants, but had completed a postgraduate training course. Patient
      opinion was obtained through questionnaires, pertaining to satisfaction and oral
      function. A comparison was made between pre-implant situation, short-term (< 4
      months) and long-term functioning (3 years) with the implant-restorative
      rehabilitation. In total, 61 patients participated in the study; 23 received a
      full lower arch bridge and 18 a full upper arch bridge, while 20 patients got
      partial bridges. Of 298 installed implants, 7 failed at abutment connection
      (2.3%) and 1 during the 3-year follow-up interval (0.3%). The study results
      indicated that a great majority of patients were very satisfied with the
      treatment. Comfort with eating, aesthetics, phonetics and overall satisfaction
      improved significantly and nearly all patients said that they would undergo the
      treatment again or recommend it to others. Patients experienced their implants as
      "natural" teeth. The conclusion is that rehabilitation ad modum Branemark, even
      in the hands of non-specialized dentists, can be of high quality, improving oral
      function and satisfying the needs and demands of patients.

PMID- 9586473
TI  - Periodontal parameters of osseointegrated dental implants. A 4-year controlled
      follow-up study.
AB  - The aim of this study was to evaluate the periodontal parameters of
      osseointegrated dental implants. The condition of the peri-implant mucosa was
      assessed using periodontal parameters, i.e., of plaque index, bleeding on
      probing, probing pocket depth, probing attachment level and Periotest scores as
      well as a radiographic parameter, over a 4-year follow-up period. 32 non
      submerged ITI dental implants, all placed in the mandible, were studied in 12
      patients who had good oral hygiene. All patients were regularly recalled at 6
      month intervals. The overall implant success rate was 100%. None of the implants
      showed any signs of inflammation, radiographic bone loss or any detectable
      mobility during the follow-up period. Methods similar to those used to evaluate
      the natural dentition were effectively employed to assess the clinical status of
      the dental implants. The diagnostic value of these parameters could not, however,
      be determined from this study due to the absence of any peri-implant tissue
      complications. The results indicated that some periodontal parameters of healthy
      peri-implant mucosa might be slightly different from healthy periodontal tissue.

PMID- 9586474
TI  - Mk II: the self-tapping Branemark implant: 5-year results of a prospective 3
      center study.
AB  - The 5-year result of a prospective 3-center study is presented, comprising 103
      patients with 288 Mk II self-tapping and 275 standard implants of the Branemark
      System. Out of 363 mandibular and 200 maxillary fixtures, one Mk II was lost of
      the lower jaw and 13 of each implant type failed in maxillae during the study
      period. Cumulative prosthesis stability was 97%. Five patients accounted for more
      than 85% of the fixture losses. Marginal bone resorption was similar for both
      implant designs. Apart from the implant failures and one patient exhibiting
      disturbed nerve sensation of the mental nerve, no major complications were
      encountered. Overall, this study revealed equal cumulative success rates for
      standard and Mk II implants after 5 years of observation. Mandibular implants
      exhibited greater success rates (100%) for both tested implant types compared to
      maxillary implants (87%).

PMID- 9586475
TI  - A comparative study of removal torque of endosseous implants in the fibula, iliac
      crest and scapula of cadavers: preliminary report.
AB  - This study was undertaken to compare removal torque of endosseous implants in the
      fibula, iliac crest and scapula of cadavers. The fibulae, iliac crests and
      scapulae were harvested from the right side of 5 formalin-preserved cadavers.
      Endosseous implants (Branemark System) were placed at 3 points of each bone. The
      removal torque of the implant was measured by a torque gauge manometer (Tohnichi
      15 BTG-N). After measurement of the removal torque, the bone was cut at each
      implant site. The thicknesses of cortical and total bone were measured. The mean
      removal torques were 46.3 N cm in the fibulae, 15.2 N cm in the iliac crests and
      21.4 N cm in the scapulae. There was a statistically significant difference in
      mean removal torque between the three bones. The total bone thicknesses were 11.7
      mm in the fibulae, 9.9 mm in the iliac crests and 8.2 mm in the scapulae. The
      cortical bone thicknesses were 5.0 mm in the fibulae, 1.6 mm in the iliac crests
      and 1.8 mm in the scapulae. Significant correlation between the removal torque
      and the cortical bone thickness was found. However there was no significant
      correlation between the removal torque and the total bone thickness. In
      conclusion, the implants inserted in the fibulae showed the highest removal
      torques as compared to the ones inserted in the iliac crests and the scapulae.
      Moreover the removal torque was related to the thickness of the cortical bone in
      the implant sites.

PMID- 9586476
TI  - An in vitro evaluation of the strength of an internal conical interface compared
      to a butt joint interface in implant design.
AB  - Dental implants are subject to large and highly complex loads of varying
      magnitude, duration and vector. Bridge performance is closely related to load
      transmission both at the bone to implant interface and between components within
      the implant-abutment-bridge cylinder complex. The design of the interface between
      components within this complex may have a profound influence on the long term
      function of the implant supported prosthesis. An in vitro evaluation of implants
      3.5 mm in diameter, utilizing an internal conical interface has demonstrated
      increased resistance to bending moments at the fixture-abutment interface (P =
      0.00010) and at the abutment-bridge cylinder interface (P < 0.01), when compared
      to a standard 3.75 mm implant with a hex mediated, butt joint interface. The
      relatively small values for coefficient of variance measured in both systems
      would confirm that whilst the size of data is small, it is nonetheless a reliable
      indication of the relative strength of these implant designs.

PMID- 9586477
TI  - Accuracy of radiographic diagnosis of peri-implant radiolucencies--an in vitro
      experiment.
AB  - The absence of a peri-implant radiolucency on radiographs is used as a criterion
      for implant success. The purpose of the present study was to evaluate the
      accuracy of diagnosing peri-implant radiolucencies using an experimental model.
      Astra Tech fixtures were inserted into 20 bony specimens. Later, the fixtures
      were removed and the prepared cavities were enlarged in 2 steps. The specimens
      were radiographed under strictly standardized circumstances in the 3 stages
      ("press-fit" = simulated osseointegration, and "0.1 mm space" and "0.175 mm
      space" = simulated connective tissue layer). All specimens were radiographed with
      2 vertical angulations (0 degree and 15 degrees). Ten observers read the
      radiographs and evaluated bone-implant relationship on a 5-point scale. The
      interobserver agreement was low. Specificity was remarkably low, and sensitivity
      was moderate. A significant difference in diagnostic accuracy was found for 0.175
      mm peri-implant-space compared to 0.1 mm space. The diagnostic accuracy was found
      to be highest for 0.175 mm peri-implant space specimens. It is concluded, that
      radiography seems to be an unreliable method for diagnosing peri-implant spaces,
      although accuracy improved at increasing space widths. Strict orthogonal
      projection angles did not improve diagnostic accuracy.

PMID- 9586478
TI  - Implant therapy involving maxillary sinus lift in periodontally compromised
      patients.
AB  - This study reports the results of implant therapy involving a sinus membrane lift
      as well as conventional implant therapy in 24 periodontally compromised patients
      who were treated during the period between June 1990 and May 1995. Patients were
      included on the basis of being in need of at least 2 implants, 1 of which was to
      be placed in the maxillary sinus region, and at least 3 mm bone height was
      required in the sinus region. Following fenestration of the lateral sinus wall
      and lifting of the sinus membrane sinus implants were inserted as described for
      conventional implants. Annual follow-up visits included recording of plaque,
      probing pocket depth and bleeding on probing, and recording of the radiographic
      distance from the implant shoulder to the alveolar crest in mm. The Astra, Astra
      sinus, ITI, and ITI sinus were observed for an average of 30.8, 29.9, 29.4 and
      25.3 months, respectively. Of the 80 implants inserted 1 Astra and 2 ITI had
      failed at 11-12 months and 1 ITI had failed at 42 months. The Kaplan-Meier
      estimate of the proportion of non-failed implants at 36 months were 100%, 95%,
      91%, and 86% for the Astra, Astra sinus, ITI, and ITI sinus implants,
      respectively. Of the Astra, Astra sinus, and ITI implants, 71-82% remained free
      from bone-loss > or = 1.5 mm at 36 months, whereas this was the case for only 29%
      of the ITI sinus implants. About 80-90% of the implants remained free from
      plaque; 65-86% remained free from bleeding; and 44-80% remained free from pockets
      > or = 4 mm. These results indicate that the sinus lift technique can be used
      successfully in periodontally compromised patients.

PMID- 9586479
TI  - Measurements of stability changes of titanium implants with exposed threads
      subjected to barrier membrane induced bone augmentation. An experimental study in
      the rabbit tibia.
AB  - The purpose of the present study was to evaluate in a rabbit model the changes in
      stability of implants that had been subjected to barrier membrane induced bone
      augmentation, as compared to untreated controls. One titanium implant was
      inserted in each proximal tibial metaphysis of 10 rabbits. The implants were
      placed in such a way that 4-5 threads on one side of the implant were left
      uncovered by bone. On the test side, the exposed implant surface was treated by
      means of a barrier membrane technique to provide for bone augmentation, while the
      contralateral side was untreated. The stability evaluations were made by means of
      resonance frequency measurements (RFM) at Day 0 and after 8, 16 and 24 weeks of
      healing. In addition, changes in the area of exposed implant threads were
      documented and measured on photographs. Removal torque measurements were
      performed at the day of sacrifice. In this study it was not possible to
      demonstrate a statistically significant better stability of implants subjected to
      barrier induced bone augmentation as compared to control implants still having
      exposed threads as evaluated by RFM and removal torque measurements.

PMID- 9586480
TI  - Guided bone regeneration around dental implants in the atrophic alveolar ridge
      using a bioresorbable barrier. An experimental study in the monkey.
AB  - The aim of this study was to evaluate guided bone regeneration (GBR) around
      dental implants placed in atrophic alveolar ridges using an experimental,
      nonporous bioresorbable barrier. In 8 Rhesus monkeys, the maxillary canines and
      lateral incisors were extracted bilaterally and the remaining alveoli were
      reduced to create atrophic ridges. After a healing period of 3 months, soft
      tissue expansion was performed using a subperiosteal tissue expander. After 1
      month of tissue expansion, and IMZ implant was placed in the atrophic ridge on
      each side in such a way that its coronal 4 mm to 5 mm remained circumferentially
      exposed above the bone level. The test implants were covered with a bioresorbable
      barrier made of poly (D,L-lactid-co-trimethylencarbonate) in a 70/30 ratio,
      whereas the control implants were covered with a nonresorbable expanded
      polytetrafluoroethylene (e-PTFE) barrier. The e-PTFE barriers were stabilized
      with titanium minipins while the bioresorbable barriers were analogously fixed
      using bioresorbable minipins made of poly (L-lactid-co-D,L-lactid) 70/30.
      Clinical healing progressed uneventfully in both groups and no soft tissue
      dehiscences occurred. Histometric and histomorphometric analyses were performed 5
      months post surgery. Both test and control implants exhibited direct bone-to
      implant contact to variable extents. The mean direct mineralized bone-to-implant
      contact length fraction was 32% of the total implant length in the test sites and
      58% in the control sites. Control sites exhibited significantly greater bone fill
      compared to the experimental sites (P < 0.001). Histologic observations of test
      specimens demonstrated a moderate inflammatory reaction related to the
      degradation and resorption products of the barrier. In conclusion, the
      nonresorbable e-PTFE GBR barrier was found to be superior to the bioresorbable
      barriers tested in the present investigation.

PMID- 9586481
TI  - The use of implant-supported titanium prostheses for treatment of periodontally
      compromised patients including functional and orthodontic therapy. Report of 2
      cases.
AB  - Due to its corrosion resistance and biocompatibility, titanium appears to be an
      alternative material for implant-supported restorations. However, due to
      technological difficulties, the clinical application of titanium in implant
      restorations has been limited. Only after recent progress in technology could the
      clinical use of ceramo-metal titanium restorations be recommended. The
      therapeutic repertoire for treating patients with missing teeth has been
      significantly expanded by modern implant methods. Osseointegrated prostheses have
      become an integral part of restorative therapy also for periodontally compromised
      dentitions. This article presents 2 case reports for the use of ceramo-metal
      implant-supported titanium cast prostheses for restorative treatment of
      periodontally compromised patients requiring comprehensive treatment involving
      periodontal, functional, orthodontic and prosthodontic therapy. Favourable
      clinical results have been obtained and a complication-free service of these
      reconstructions has been documented throughout a 12- to 24-month observation
      period. These observations suggest that implant-supported ceramo-metal titanium
      prostheses may be a valuable part of restorative therapy for periodontally
      compromised dentitions in that they facilitate restorations with optimal
      biocompatibility. However, controlled clinical studies are needed to establish
      the long-term serviceability of these titanium restorations.

PMID- 9586482
TI  - Why NIH is wrong about "TMD".

PMID- 9586483
TI  - Back to the basics.

PMID- 9586484
TI  - Dr. Shulman responds to Dr. Moses's "Good science, bad science" editorial in July
      1996 CRANIO.

PMID- 9586485
TI  - Masticatory tooth contact patterns: predicted and observed cuspid and first molar
      contacts in cuspid and group function.
AB  - Using the mouth as an "in vivo articulator," the bilateral nonmasticatory
      ("empty") contact patterns of opposing cuspid and first molar teeth were
      determined in two healthy subjects with well-defined cuspid function and two
      healthy subjects with well-defined group function. The electronically recorded
      "empty" contact patterns pertained to the static intercuspal position and dynamic
      laterotrusion to the right and the left. On the basis of the "empty" tooth
      contact patterns and the number of electronically recorded masticatory cycles of
      one masticatory sequence, we postulated two simple models that attempted to
      predict the masticatory ("functional") tooth contacts of one sequence of
      unilateral mastication of apple and banana. Statistical comparisons between the
      predictions of the two models and the actual ("functional") contacts of in vivo
      mastication showed that the models predicted fairly well the observed tooth
      contacts on the nonchewing-side of the mouth, but not the observed tooth contacts
      on the chewing-side of the mouth. In consequence, "empty" (nonmasticatory) tooth
      contact patterns should not be equated with "functional" (masticatory) tooth
      contact patterns.

PMID- 9586486
TI  - A comparison of ICAGD (immediate complete anterior guidance development) to mock
      ICAGD for symptom reductions in chronic myofascial pain dysfunction patients.
AB  - The purpose of this study is to assess what impact shortening disclusion time to
      less than .5 seconds during right and left mandibular excursions has on
      myofascial pain(s) symptoms present in a dental student population. Twenty-five
      dental students, who exhibited symptomatology consistent with myofascial pains
      patient, were divided into a treatment, control, and an untreated group. They
      participated in an occlusal adjustment study which measured changes in disclusion
      time, as well as, myofascial pains muscular symptom remissions resultant from
      treatment. The treated group of ten subjects received ICAGD occlusal adjustments
      to shorten their disclusion time to less than .5 seconds per mandibular
      excursion. The goal of this therapy was to totally disclude the posterior teeth
      in a measurable time frame of .5 seconds or less. The control group of eight
      subjects received mock ICAGD with tooth polishing. The goal of this therapy was
      to simulate ICAGD adjustments for possible placebo effect on symptom remissions.
      The untreated group had their disclusion times measured but received no treatment
      to adjust, or to simulate adjustment to their occlusion. The goal of analyzing an
      untreated group was to attempt to show that mock treatment (performed on the
      control subjects), or no treatment (performed on the untreated subjects),
      resulted in no measurable change in the disclusion time in either of these two
      subject groups. Each subject was recalled for disclusion time measurement four to
      five times in a one-year period of observation, at which time, they were required
      to report their myofascial pains symptom status by answering an ordinal scale
      questionnaire. The results suggest that shortening disclusion time to less than
      .5 seconds per mandibular excursion can induce remissions of many muscular
      myofascial pains symptoms. Additionally, mock ICAGD occlusal adjustments did not
      appear to be a factor in the control subjects treatment response, as this group
      showed no statistically significant symptom remissions.

PMID- 9586487
TI  - The role of the lateral pterygoid muscles in TMJ disorders during static
      conditions.
AB  - Intramuscular EMG of the lateral pterygoid muscles (LPM), surface EMG of the
      temporalis and masseter muscles and force measurements of the temporomandibular
      joint (TMJ) were synchronously used to investigate the biomechanical role of the
      two heads of the LPM in relation to internal derangement (ID) of the TMJ. EMG and
      kinetic analysis of five static conditions (resting, protraction, opening, molar
      and incisor clenching) and three maximum isometric masticatory forces (opening,
      molar and incisor clenching) were done to compare forces and muscular activity
      between TMJ ID and control subjects. The analysis of variance results of the
      integrated linear envelope (LE) EMG showed no significant differences between the
      two groups for the masseter and temporalis muscles. Therefore, there is no
      apparent reason to believe that these muscles are hyperactive in TMJ ID. The
      integrated LE EMG of the SLP was significantly lower in the TMJ group during
      molar clenching (104 microV + 60.0 over 159 microV + 68.8 for a p = .020). The
      superior head of the lateral pterygoid muscle (SLP) seemed to have lost its
      diskal stabilizing function. The integrated LE EMG signals of the ILP were
      significantly higher in the TMJ ID group during rest, resisted protraction and
      incisor clenching (p = .029, p = .046, p = .031 respectively). The ILP muscle has
      probably adapted to control the inner joint instability while continuing its own
      actions. The ILP muscle seemed to have lost its functional specificity. The
      results of the isometric forces showed that TMJ ID subjects exhibited
      significantly lower molar bite forces (297.1N over 419N, p = .042) confirming
      that they have less muscle strength and tissue tolerance than subjects with
      healthy masticatory muscle systems. A neuromuscular adaptation could be occurring
      in the TMJ ID masticatory system affecting muscular actions and forces.

PMID- 9586488
TI  - The use of tricyclic antidepressants for the control of chronic orofacial pain.
AB  - Tricyclic antidepressants, or "tricyclics" as they are commonly called, are
      effective in reducing pain in chronic neurological and musculoskeletal disorders.
      Tricyclics appear to be effective in the control of chronic orofacial pain of non
      inflammatory origin, and include amitriptyline, doxepin, nortriptyline and
      desipramine. Daily doses of the medications are smaller for the management of
      pain than doses typically used in the treatment of depression. Certain medical
      conditions may contraindicate tricyclic trials, while others may warrant starting
      at a lower dose with more conservative dose adjustments. Common side effects
      include dry mouth, sedation, constipation and orthostasis. Tricyclics are just
      one therapeutic modality which can be considered in the management and treatment
      of chronic refractory orofacial pain that is suspected to arise from neurogenic
      or myofascial etiologies.

PMID- 9586489
TI  - Effect of increased maxillo-mandibular relationship on isometric strength in TMD
      patients with loss of vertical dimension of occlusion.
AB  - The effect on isometric strength of the shoulders and limbs while biting in
      habitual occlusion, on a bite-elevating appliance and on a placebo appliance was
      analyzed. Twenty female volunteer patients, presenting with temporomandibular
      pain dysfunction syndrome and obvious loss of vertical dimension, served as
      subjects. All were weaker to the manual application of the isometric Deltoid
      Press (IDP) when biting, as opposed to maintaining the mandible in an unsupported
      rest position. Two intraoral appliances were fabricated for each subject: a bite
      elevating appliance (BEA) set by a functional criterion of peak strength to the
      IDP and a placebo appliance which did not interfere with occlusion but was "set"
      with a mock IDP procedure. Testing was carried out by the Neuromuscular Research
      Testing Laboratory of the Neurology Department of Tufts New England Medical
      Center. Testing was independent of the dentist who fabricated and set the
      appliances. A standard neuromuscular test with the Maximal Voluntary Isometric
      Contraction apparatus was used to assess strength of right and left shoulder,
      elbow and knee flexion and extension as is routinely performed with all
      neuromuscular disease patients. Twelve strength tests were carried out for each
      of three conditions: 1. Baseline-biting in habitual occlusion; 2. Elevated-biting
      on the BEA; and 3. Placebo-biting with the placebo appliance inserted. The order
      of conditions 2 and 3 was counterbalanced without knowledge of the subjects.
      Twelve repeated measures ANOVAs (each subject as their own control) were
      conducted for each of the 12 strength measures. All F-tests indicated a
      significant main effect for treatment differences (p < 0.0001). Mean strength
      biting on the BEA was consistantly greater (p < 0.001) than Baseline or Placebo
      strength. Baseline and Placebo condition were equivalent. These findings
      confirmed previous observations at this TMD Center: individuals with loss of
      vertical dimension of occlusion respond to a bite raising appliance by increased
      isometric-strength.

PMID- 9586490
TI  - Snoring and obstructive sleep apnea: does head posture play a role?
AB  - The aim of this article is to present scientific and clinical evidence to support
      the role of proper head and neck posture in the management of snoring and
      obstructive sleep apnea. Obstruction of the upper-airway during sleep is a
      serious medical condition often associated with severe daytime somnolence,
      morning headache, and a host of cardiopulmonary complications, including but not
      limited to systemic and pulmonary hypertension, nocturnal cardiac dysrhythmias,
      myocardial infarction, and stroke. Though anti-snoring pillows are occasionally
      mentioned in the literature, the role of proper head-neck support during sleep
      has been largely neglected. In this article the effect of head-neck position on
      upper-airway obstruction during sleep is discussed from the perspective of both
      causation and treatment. Based on the evidence presented by the author, it is
      recommended that the use of cervical-support pillows be considered as an
      adjunctive treatment modality in patients suffering from snoring and obstructive
      sleep apnea.

PMID- 9586491
TI  - The important role of motion in the rehabilitation of patients with mandibular
      hypomobility: a review of the literature.
AB  - The orthopedic literature has clearly demonstrated that the physical stimulus of
      motion is essential for the maintenance of the structural and functional
      integrity of synovial joints. As a result of this information, rehabilitation
      with passive motion has become an extremely important part of the rehabilitation
      of synovial joints throughout the body, especially when there is limited range of
      motion. This same biological principle must be applied to the temporomandibular
      joint, especially when there is limitation in mandibular mobility. The effects of
      limited joint mobility, as well as passive motion, on the articular and extra
      articular components of synovial joints is reviewed in detail. The clinical
      application of these principles in the management of temporomandibular disorders
      is emphasized.

PMID- 9586493
TI  - Cluster-like signs and symptoms respond to myofascial/craniomandibular treatment:
      a report of two cases.
AB  - Two cases with pain profiles characteristic of cluster-like headache, both within
      and outside the trigeminal system, are reported. One male patient would typically
      awaken from sleep with severe unilateral temporal head pain and autonomic signs
      of ipsilateral lacrimation and nasal congestion. A female patient exhibited
      severe unilateral boring temporal and suboccipital head pain with associated
      ipsilateral lacrimation and rhinorrhea. In addition, both patients presented with
      signs and symptoms of masticatory and/or cervical disorders. These two cases
      illustrate possible treatment alternatives, as well as possible influences from
      cervical and masticatory structures in the development of cluster or cluster-like
      headache.

PMID- 9586492
TI  - Anterior mandibular repositioning in a patient with temporomandibular disorders:
      a clinical and tomographic follow-up case report.
AB  - A 42 year old female with temporomandibular disorders (TMD) was treated by
      anterior mandibular repositioning which was followed-up clinically and
      tomographically. The authors tomographically reconfirmed the mandibular
      repositioning and discovered a type of condyle remodeling which they had not seen
      previously. Although clinical signs and symptoms of TMD were removed and the
      condyle was centered tomographically by the anterior repositioning, the MRI image
      indicated the disk was displaced anteriorly and laterally. The results suggest
      that image analysis of temporomandibular joint (TMJ) is beneficial and careful
      application of the treatment for anterior repositioning is recommended.

PMID- 9586494
TI  - Considerations before surgical intervention in management of temporomandibular
      joint disorders.
AB  - In summary, reviewing the patients history, re-examining the patient, re
      evaluating the imaging findings, evaluating prior treatment, incorporating
      additional treatment, exploring other possible contributing factors, and
      screening the patient's level of cooperation can lead to discovery of additional
      issues which may, when properly handled, result in successful nonsurgical
      treatment and avoid unnecessary surgeries.

PMID- 9586495
TI  - The field of orofacial pain: should it be a specialty?

PMID- 9586496
TI  - What will the self-anointed elite destroy next?

PMID- 9586497
TI  - Flatau challenges Dunn, et al.'s priority claim to the discovery of the
      sphenomandibularis muscle.

PMID- 9586498
TI  - Tendon and ligament insertions--a possible source of musculoskeletal pain.
AB  - In many cases of musculoskeletal pain, the source of the pain is still elusive as
      indicated by the number of acceptable, but different types of treatments that are
      available. Within the musculoskeletal system, the tendino-periosteal attachment
      of the muscles (enthesis) appears to be an area that is especially susceptible to
      injury as a result of trauma. Because it is a structurally flawed, richly
      innervated, and metabolically active area, it may be the "weakest link" and most
      reactive site in the musculoskeletal system. Following episodes of trauma,
      lesions at the enthesis may result in a wide range of symptoms. Treatment of
      these lesions may be crucial to the success of post-traumatic pain management.

PMID- 9586499
TI  - Perspectives on the role of the lateral pterygoid muscle and the sphenomandibular
      ligament in temporomandibular joint function.
AB  - The lateral pterygoid muscle plays an important role in the movement of the
      mandible and has been studied from several points of view, including structural
      and functional anatomy. What matters clinically is the relative position of the
      muscle fibers attached medially to the mandibular condyle. In the following
      study, we observed not only the attachment of the lateral pterygoid muscle fibers
      to the articular disk, but also the relative position of the mandibular condyle
      to a base line set up on the mandibular condyle. According to our observations,
      the lateral pterygoid muscle fibers attach to the articular disk at the inner
      point of the medial pole. Based on this finding, we can say that the muscle
      fibers can both draw the articular disk anteriorly and balance it by supporting
      it posteriorly. That is to say, the lateral pterygoid muscle has two actions: to
      elevate the articular disk anteriorly and to support the articular disk.
      Furthermore, the sphenomandibular ligament has continuity with the articular disk
      tissue medially. This relationship suggests that the ligament fibers attached to
      the articular disk draw the disk posteriorly in its course of mandibular closing,
      thus enabling the articular disk to move smoothly.

PMID- 9586500
TI  - Chewing movements in near ideal occlusion with and without TM symptoms.
AB  - Orthodontic models hand-articulated into maximum intercuspation of 720 untreated
      subjects were evaluated by 17 criteria for grading an ideal anatomic occlusion
      including good dental interdigitation and alignments. Of the 720 subjects
      screened, the best 17 subjects were divided into three groups that contained 11
      near ideal occlusions scored with 92-98%, three lower evaluated occlusions scored
      with 86-88% and three near ideal occlusions with TM signs or symptoms scored with
      90-94%. Border and chewing movements were recorded using incisor tracking
      instrument (Visitrainer, model 3). Border movements in asymptomatic subjects
      demonstrated a well-defined intercuspal position, smooth and equal lateral
      excursions, and straight opening/closing movements. However, one subject with
      pain of right joint recorded an inconsistent intercuspal position, restricted
      excursions and a deviated path corresponding to a reciprocal click in
      opening/closing movements. Chewing movements in asymptomatic subjects with near
      ideal occlusion demonstrated either no or a lower rate of opening gliding tooth
      contact along the lateral border movement on non-working side, and a higher rate
      of closing gliding tooth contact along border movement on the working side.
      Chewing movements in symptomatic subjects with near ideal occlusion showed
      opening and closing without gliding along the lateral excursions, and closing
      point was inconsistent with maximum intercuspal position in the pain subject. In
      examining these near ideal occlusion subjects, the different characteristic
      chewing and border movements were defined for subjects with and without TM
      symptoms, respectively. Asymptomatic subjects with near ideal occlusion and lower
      evaluated occlusion showed almost the same chewing function. The goal of
      orthodontic treatment might be anatomic ideal occlusion with good chewing and
      border movements indicated in this study.

PMID- 9586501
TI  - Increase of the vertical occlusal dimension by means of a removable orthodontic
      appliance and its effect on craniocervical relationships and position of the
      cervical spine in children.
AB  - The aim of this study was to determine the effect of the increase in the occlusal
      vertical dimension by means of an orthodontic appliance on craniocervical
      relationships and position of the cervical spine. Thirty children presenting
      malocclusion were divided into two groups of 15 (a study and a control group).
      Those in the study group wore an orthodontic appliance to correct cross-bite. The
      children in the control group had no treatment during the experimental period.
      Two lateral craniocervical radiographs were taken for each child. The first one
      was taken in the intercuspal position in both groups. The second radiograph was
      taken of the study group after four months of wearing the appliance and also of
      the control group after four months. Cephalometric analysis in the study group
      showed a significant forward cervical spine position. There were no significant
      changes in the control group. The changes found in the study group suggest that
      when there are signs and symptoms of cervical dysfunction in children undergoing
      long-term orthodontic treatment, it is necessary to make an evaluation of the
      cervical column position after the insertion of any orthodontic appliance which
      increases the occlusal vertical dimension.

PMID- 9586502
TI  - The clinical significance of the horizontal condylar angle in patients with
      temporomandibular disorders.
AB  - Ninety-one patients with unilateral temporomandibular disorders (TMD) were
      examined using submento-vertex projection radiography and lateral and frontal
      temporomandibular joint (TMJ) tomography. A comparison between clinical and
      radiographic findings was made to verify whether patients with TMJ
      osteoarthritis/osteoarthrosis (OA) tend to have high horizontal condylar angles
      and to determine the clinical significance of the horizontal condylar angle in
      the diagnosis of TMD. Our survey results did not confirm higher horizontal
      condylar angles in condyles with radiographic abnormal findings than in those
      with normal. However, significantly higher angles were observed in symptomatic
      TMJs with pain on movement/palpation than in those without (P < 0.05). A tendency
      toward higher angles was also observed in patients with other clinical findings
      such as TMJ sound on the symptomatic side and limitation of mouth opening, but
      there were no significant differences. Thus, the clinical significance of
      measuring the horizontal condylar angle was demonstrated. Careful diagnosis and
      treatment is therefore recommended with patients for whom the horizontal condylar
      angle is high.

PMID- 9586503
TI  - Elongated styloid process: diagnostic problems related to symptomatology.
AB  - A certain number of patients with elongated styloid process may not have the
      classic cervicofacial complaints which were originally described by W. Eagle in
      1937. Some of those cases who have radiologic evidence of elongated styloid
      process are symptom free and can be accepted as normal anatomical variants. On
      the other hand, some of those symptomatic cases may present uncommon neurologic
      signs and can be misdiagnosed as neurologic or infectious disease. Sometimes, the
      radiologic presence of an elongated process may cause the clinician to miss
      another pathology. Therefore, it is essential for the clinician to be aware of
      the clinical variants with different symptomatology or to particularly seek the
      origin of the pain in the head and neck before reaching a conclusion, since the
      only effective treatment in symptomatic cases is the surgical shortening of the
      process. We report five patients with elongated processes. Problems related to an
      elongated styloid process with different symptomatology are discussed and the
      associated literature is reviewed.

PMID- 9586504
TI  - Reflex jaw motions and jaw stiffness pertaining to whiplash injury of the neck.
AB  - Because a so-called mandibular whiplash injury requires the absence of short
      latency jaw-closing reflexes in order to explain the postulated mechanism of
      injury (excessive jaw opening); the authors studied the presence and absence and
      more importantly, the kinematics (duration, displacement, velocity, acceleration)
      of monosynaptic and possibly, polysynaptic myotatic (stretch) reflexes in the jaw
      elevator muscles. In six healthy adults jaw jerk maneuvers were elicited through
      a brisk tap on the chin, and surface electromyography identified elevator
      reflexes while translational electrognathography identified the kinematics of the
      reflexes. The maneuvers were done while maintaining the rest position (3% MVC)
      and moderate clenching of the teeth (30% MVC). Electromyography was also used to
      identify phasic elevator excitations during a passive brisk neck extension
      maneuver. A sudden and unexpected elongation of the jaw elevators released
      autogenic reflex responses that, in conjunction with augmented tissue elasticity
      (stiffness), elevated the mandible into centric occlusion within approximately
      150 milliseconds. In 86% of trials, the responses occurred regardless of the
      prevailing resting and clenching contractile activities. There was no evidence of
      a depressor force that consistently would and could anchor the mandible in a
      position of extreme or moderate depression, the theoretical linchpin of the
      mandibular whiplash injury. It was concluded that the mandibular locomotor system
      is very efficient in maintaining the rest and intercuspal positions of the
      mandible. This study found no evidence corroborating the mechanism claimed to
      release a so-called mandibular whiplash injury.

PMID- 9586505
TI  - Cognitive factors associated with facial pain.
AB  - Most well-accepted etiological models of facial pain (e.g., temporomandibular
      disorders and headache) implicate emotional distress as an important factor in
      the development and maintenance of pain. Data exists to support the notion that
      some facial pain sufferers are more emotionally distressed than no pain controls.
      However, many of these dependent measures of emotional distress are either
      lengthy assessment batteries, lack clear cut psychotherapeutic treatment
      implications, or focus exclusively on pain related sequela. As cognitive
      behavioral interventions become more integrated into the treatment of chronic
      pain conditions, including various facial pain conditions, it becomes more
      imperative that the tools used to assess psychological functioning provide the
      clinician with specific cognitive/behavioral targets for change. The purpose of
      this study was to assess the degree to which symptomatic treatment seeking facial
      pain sufferers (N = 25), symptomatic non-treatment seeking facial pain sufferers
      (N = 48), and healthy pain-free controls (N = 70) differed on the Rational
      Beliefs Inventory (RBI). The RBI is a reliable, valid questionnaire assessing
      rational beliefs that are operationalized within a Rational Emotive Therapy (RET)
      framework. RET is a cognitive-behavioral treatment paradigm that focuses on how
      an individual's maladaptive cognitive errors or distortions exacerbate emotional
      distress. Group differences were assessed using a oneway Analysis of Covariance
      (ANCOVA) with the total RBI score serving as the dependent measure, and a
      Multivariate Analysis of Covariance (MANCOVA) using individual RBI belief
      subscales as dependent measures. These results indicated that groups differed
      significantly on the total score and several of the individual belief subscales.
      These findings indicated that facial pain sufferers generally hold maladaptive
      beliefs that may be of clinical significance for cognitive/behavioral treatment
      approaches.

PMID- 9586506
TI  - Ehlers-Danlos syndrome, fibromyalgia and temporomandibular disorder: report of an
      unusual combination.
AB  - An unusual case of temporomandibular disorder in the presence of both
      fibromyalgia and Ehlers-Danlos syndrome is presented. Some of the problems in
      treating these patients are discussed. It is suggested that early conservative
      treatment of the temporomandibular disorder with a stabilization splint and
      physical therapy is effective, and this approach should be attempted before any
      surgical intervention is chosen.

PMID- 9586507
TI  - The future of dentistry and dentistry's involvement in the diagnosis and
      treatment of nonodontogenic pain problems involving the stomatognathic system
      (jaw and related structures)

PMID- 9586508
TI  - Moving toward maturity.

PMID- 9586509
TI  - Dr. Uppgaard expresses hope in the battle for fair insurance coverage for TMD.

PMID- 9586510
TI  - Dr. Bever underscores Dr. Dawson's January '97 editorial.

PMID- 9586511
TI  - Setting the record straight.

PMID- 9586512
TI  - Mandibular repositioning can be effective in treatment of reducing TMJ disk
      displacement. A long-term clinical and MR imaging follow-up.
AB  - In order to evaluate the long term clinical and morphologic results of recapture
      of a displaced TMJ disk, we recalled for follow-up MR imaging 75 patients who had
      been treated by attempted disk recapture based on pre-treatment MR imaging 1-6
      years earlier. The treatment included a day appliance with inclines to guide the
      mandible into the therapeutic position and a telescopic night appliance which
      prevented retrusion of the mandible during sleep. Appliance treatment was
      followed by rebuilding or resurfacing the posterior teeth of one arch to
      permanently support the mandible in the therapeutic position. After treatment of
      115 joints with displaced disks, 52% of the disks were normally positioned, 23%
      were improved in position, and 25% showed persistent disk displacement. Symptom
      relief was 92% in patients with normalized (recaptured) disks, 84% in patients
      with improved disk position, and 49% in patients with persistent disk
      displacement. Failure to improve disk position occurred in 7% of the joints with
      anterior disk displacement and in 44% of the joints with a transverse (sideways)
      component to the displacement. Forty-five percent of the recaptured-disks
      improved in contour. We concluded that anterior mandibular repositioning was
      effective in the treatment of patients with reducing displaced disks primarily
      when the disks were displaced only in an anterior direction. This treatment can
      be recommended in anterior disk displacements if the patient has failed more
      conservative treatment measures, permanent occlusal reconstruction can be
      justified, and the patient understands that long-term use of a night appliance
      may be necessary. Anterior mandibular repositioning appears much less effective
      in cases with a transverse component to the disk displacement.

PMID- 9586513
TI  - TMJ clicking: a comparison of clinical examination, sonography, and axiography.
AB  - A sample of 30 subjects, 15 with and 15 without subjective temporomandibular
      joint (TMJ) complaints (noises, sounds), underwent a clinical examination, a
      sonography and an axiography, to detect TMJ clicking. The clinical examination
      found 22 noisy joints in a total of 60 TMJs considered. Axiography found 19 noisy
      joints and sonography 32. While 90% of the examined joints showed agreement
      between axiography and clinical examination (with a little higher sensitivity
      demonstrated by clinical examination with respect to axiography), 20% of the
      joints were positive for clicking in sonography only. Sonography showed a high
      sensitivity in detection of joint noises which suggests its utility as a
      screening test for early detection of craniomandibular disorders.

PMID- 9586514
TI  - Effect of occlusal splint on masticatory movement in healthy individuals.
AB  - To investigate the effects of wearing an occlusal splint on masticatory movements
      in healthy individuals, twelve healthy individuals were examined. A full
      maxillary stabilization splint made of heat-cured acrylic resin was fabricated
      for, and worn by, each individual for 24 hours. Masticatory movement was measured
      before and after the 24-hour period using a 3-D mandibular movement analyzing
      system. While the duration of a masticatory cycle+ did not change, the occlusal
      time significantly decreased after use of the splint. The lateral displacement of
      the opening phase to the balancing-side area also decreased after use of the
      splint, showing a vertical pattern of the opening path. Measurement in more
      healthy individuals and patients should help clarify the therapeutic mechanism of
      the splint in the treatment of temporomandibular disorders.

PMID- 9586515
TI  - Effectiveness of the Michigan splint in reducing functional cervical
      disturbances: a preliminary study.
AB  - There is controversial evidence for a functional link between the masticatory
      apparatus and the cervical spine. The aim of this work was to perform a
      preliminary study to evaluate the effectiveness of the Michigan splint for the
      treatment of functional cervical disturbances. Forty patients with functional
      cervical disturbances were randomly organized into test and control groups. The
      patients in each group were examined by a physiologist to ascertain the extent of
      functional changes. The test group underwent splint therapy (Michigan type)
      during a two-month period. The other patients were sent home and did not receive
      active treatment. After two months, all patients were reassessed physiologically.
      Cervical pain and pain induced by epispinal or paraspinal pressure were reduced
      to a statistically significant extent in the treated group, compared with those
      in the control group.

PMID- 9586516
TI  - The relationship of tinnitus to craniocervical mandibular disorders.
AB  - Patients with craniocervical mandibular (TMD) disorders can present with tinnitus
      as a primary or secondary complaint. The embryology and functional anatomy of the
      middle ear, temporomandibular joint, muscles of mastication and associated
      tendons, ligaments, blood vessels, nerves and lymphatics was found to be helpful
      in establishing etiologic concepts which relate tinnitus to these
      temporomandibular disorders. In addition to etiologic concepts, treatment
      modalities are described. The authors relate their experiences as well as those
      of others with different patient populations.

PMID- 9586517
TI  - Low level laser therapy in the treatment of temporomandibular disorders (TMD): a
      double-blind pilot study.
AB  - The aim of this paper was to evaluate the efficacy of a Low-Level Laser therapy
      in patients with Temporomandibular Disorders (TMD) using a double-blind design. A
      sample of 20 patients with a chief complaint of pain was divided into myogenous
      and arthrogenous groups. The sample was also divided on the basis of the
      treatment rendered: real versus placebo treatment. An 830 nm Ga-Al-As Laser
      device with a energy power of 4 joules was used (OMNILASE, LASERDYNE PTY LTD.) in
      three treatment sessions. To evaluate the effectiveness of laser treatment, a
      Visual Analogue Scale (VAS) was used for pain and active range of motion (AROM)
      was used to measure changes in mandibular function. Using real laser treatment,
      the author found that there was a reported improvement in pain only for the
      myogenous pain patients (p < or = 0.02). For the arthrogenous pain patients, real
      laser treatment resulted in an improvement in Total Vertical Opening (TVO) (p <
      0.05), Protrusive excursion (PROT) (p < 0.02) and Left lateral excursion (LATLEF)
      (p < 0.02). The placebo control group showed improvement in TVO and PROT for
      those patients having myogenous pain and LATLEF for those patients having
      arthrogenous pain. A repeated measurement one-way ANOVA demonstrated no
      significant differences between real and placebo groups. Considering the non
      invasive and harmless characteristics of this modality, more research is
      recommended, using higher power and increased frequency of laser applications.

PMID- 9586518
TI  - Medical claims profiles of subjects with temporomandibular joint disorders.
AB  - The primary goal of this study was to evaluate the claims profiles of subjects
      with TMJ disorders relative to a control group without the disorders and to
      provide a characterization of the type of healthcare services received and the
      associated costs of healthcare for patients with TMJ disorders. The
      administrative data base of a major medical insurer was used to compare the
      claims history of 1,819 patients diagnosed with TMJ disorders to matched
      controls. The analysis was based only on medical claims. The study found that
      total medical claim payments for the patients with TMJ disorders were double that
      of the subjects without TMJ disorders, and similarly, the utilization of
      institutional and professional care services was found to be approximately twice
      as high, though not uniformly distributed across all Major Diagnostic Categories,
      physician specialties or types of service. The level and nature of the
      differences in the quantity and costs of healthcare between subjects with and
      without TMJ disorders were unexpectedly large. The majority of these differences
      were attributed to conditions that were not usually considered related to TMJ
      disorders. These utilization and cost differences extended, in varying degrees,
      over a wide range of diagnostic and healthcare provider categories.

PMID- 9586519
TI  - Use and effectiveness of splint appliance therapy: review of literature.
AB  - Interocclusal orthopedic appliances of varied design and application have been
      employed in the treatment of myofascial pain dysfunction (MPD) and
      temporomandibular joint disorders (TMD). These appliances provide the
      practitioner with a non-invasive, reversible form of intervention to manage the
      patient's symptoms. Literature on the use and effectiveness of these appliances
      has become readily available and now requires retrospective evaluation. However,
      comparison of results from studies making use of interocclusal orthopedic
      appliance therapy is difficult due to the employment of various outcome
      measurement scales, subjective evaluation of patient outcome, and variability in
      reporting of treatment outcomes. The aim of this paper is to review the effects
      and success rates of the various appliances reported in the literature and
      provide the practitioner with useful information that may be of assistance in the
      prediction of outcome and success of splint appliance therapy.

PMID- 9586520
TI  - Chest cancer refers pain to face and jaw: a case review.
AB  - The dentist's sphere of treatment is generally limited by state law to the teeth,
      alveolar process, gums, cheeks, jaws or oral cavity and associated structures.
      However today, an appreciation of the total person is necessary. Pain referred
      from the chest to the face and jaw is presented to the new student when first
      assuming responsibility for treatment of the clinic patient. With contemporary
      dental practice expanded to orofacial pain and the temporomandibular joint area,
      general medical knowledge is essential. Without hesitancy, when the situation is
      not distinct, referral for medical consultation may be the best part of patient
      care.

PMID- 9586522
TI  - Narrative report for a patient with orofacial pain or temporomandibular disorder.

PMID- 9586521
TI  - Guide to evaluation of permanent impairment of the temporomandibular joint.
      American Academy of Head, Neck and Facial Pain; American Academy of Orofacial
      Pain; American Academy of Pain Management; American College of Prosthodontists;
      American Equilibration Society and Society of Occlusal Studies; American Society
      of Maxillofacial Surgeons; American Society of Temporomandibular Joint Surgeons;
      International College of Cranio-mandibular Orthopedics; Society for Occlusal
      Studies.

PMID- 9586523
TI  - Periodontal health status of patients attending Diabetic Clinic at Kenyatta
      National Hospital, Nairobi, Kenya.
AB  - The periodontal health status of diabetic patients and the association between
      periodontal disease and treatment mode, age and duration of diabetes were
      investigated in 86 dentulous men and women aged between 20 years and 69 years. 43
      were diabetics regularly controlled at Kenyatta National Hospital Diabetic Clinic
      and 43 were non-diabetics attending medical outpatient clinic at the same
      hospital for minor ailments. Diabetic patients were found to have significant
      severer levels of periodontal disease than the non-diabetics. The difference
      persisted with increasing age. No correlation was found between treatment mode
      and duration of diabetes on one hand and the severity of periodontal disease on
      the other.

PMID- 9586524
TI  - Characteristics of dental fear amongst dental and medical students.
AB  - A survey using a modification of the Dental Fear Survey (3) was carried out among
      304, 17-22-year-old college students in Mangalore, India, in order to determine
      the prevalence and characteristics of dental fear. Feeling tense was found to be
      the most frequently reported physiologic arousal. Among the dental situations,
      the needle and the drill were the most fear-provoking stimuli. About 51% of the
      students reported some fear of dentistry with females and dental students being
      more fearful than males and medical students. They also reported higher avoidance
      behaviour. This study also suggested that dental fear could be influences by
      family and friends.

PMID- 9586525
TI  - Granular cell tumour. A case report.

PMID- 9586526
TI  - Metastatic malignant melanoma of maxillary gingiva. A case report.
AB  - Malignant melanoma of the oral cavity can be primary or secondary due to
      metastasis from distant site. Incidence of oral cavity by metastasis of melanoma
      is 1.85%. Most common oral sites involved are tongue, buccal mucosa and parotid
      gland. Oral lesions occur as a part of disseminated disease during the advanced
      stages and has poor prognosis. An unusual case of metastatic malignant melanoma
      of the maxillary gingiva is reported.

PMID- 9586527
TI  - Non-extraction treatment of a 17-year-old female with a Class-II open bite dental
      and skeletal pattern.

PMID- 9586528
TI  - The orthodontic examination and diagnosis (continued).

PMID- 9586529
TI  - Treatment of an adult male with a Class II division 2 deep bite and missing upper
      first bicuspids.

PMID- 9586531
TI  - Evaluation of tapered-end toothbrushes regarding subgingival access efficacy.
AB  - The purpose of this in vitro study was to determine how two toothbrushes with
      highly tapered-end bristle designs compared to a conventional, slightly tapered
      toothbrush. Toothbrushing was carried out in the laboratory in order to evaluate
      the simulated subgingival efficacy of the three toothbrush designs. The
      performance of the three brushes was assessed by measuring the "subgingival
      regions" of gold-coated typodont left maxillary central teeth where the gold
      coating had been removed during brushing. The two toothbrushes with highly
      tapered bristles were statistically significantly (p < 0.01) more effective in
      removing the gold coating than the conventional toothbrush with slightly tapered
      bristles on the subgingival area on the anterior typodont teeth.

PMID- 9586530
TI  - Plaque removal efficacy of a newly developed powered toothbrush in the primary
      dentition of pre-school children.
AB  - A cross-over, single-blind clinical study was performed to compare a powered and
      a manual toothbrush for their ability to remove plaque from the teeth of pre
      school children. Seventy-three randomly selected 4- to 6-year-old children from
      two kindergarten classes in Erfurt, Germany participated in the study. A new
      powered children's toothbrush (Rowenta) and a currently marketed manual
      children's toothbrush (Elmex) were used for an assessment period of two weeks
      each. Then the groups were crossed over to use the alternate toothbrush for
      another two weeks. Whole mouth, gingival margin and interproximal plaque area
      levels were determined using the Rustogi et al. plaque index. Statistical
      analysis of the data showed significantly effective (p < 0.05) plaque removal
      with both toothbrushes, immediately after toothbrushing and at one and two weeks,
      compared to the respective baseline scores. The statistical analysis also
      demonstrated that the powered toothbrush was significantly (p < 0.05) better on
      percent plaque reduction on all tooth areas compared to the manual toothbrush,
      except at two weeks with the interproximal assessment.

PMID- 9586532
TI  - Chewing gum and saliva in oral health.
AB  - The crucial role played by many properties of saliva in preventing dental caries,
      maintaining the plaque pH and controlling the equilibrium between enamel de- and
      remineralization has been demonstrated. This has been documented by the effects
      of salivary dysfunction on caries incidence and by the distribution of sites of
      caries predilection in areas where saliva presence is restricted. The use of
      sugar-free chewing gum has been increasingly accepted as one adjunct to oral
      hygiene procedures. It has become part of an anti-caries prevention program,
      especially in patients suffering from xerostomia. Chewing gum not only acts as a
      salivary stimulant but may also be a useful vehicle for some agents such as
      fluoride, chlorhexidine and calcium phosphate. Moreover, in some countries gum
      containing nicotine has been used to substitute the nicotine from cigarettes to
      reduce the effects of nicotine withdrawal reaction from people attempting to stop
      smoking.

PMID- 9586533
TI  - Oral malodor in beagles: association with indicators of periodontal disease.
AB  - The study of oral malodor continues to receive attention. Most bad breath is of
      oral origin and can be corrected with proper oral hygiene. Studies performed with
      saliva from people with periodontal disease and from healthy individuals showed
      that saliva from diseased patients produced a more objectionable odor faster than
      that of healthy people, and that the volatile sulfur components (VSC) produced
      may actually play a role in the etiology of periodontal disease. However, not all
      people or animals with bad breath have periodontal disease. The objectives of
      this study were to determine if a trained panel could discriminate between 10
      dogs with clinically defined periodontal disease and those with relatively
      healthy periodontium. Second, this study attempted to establish a correlation
      between odor intensity and six clinical parameters of oral health. The judges
      were able to differentiate between the two groups of dogs based only on oral
      malodor (p < 0.02). There were strong associations of the intensity of oral
      malodor with oral health index scores. The correlations established between odor
      and gingivitis (r = 0.81) and between odor and furcation exposure (r = 0.88) were
      very high and statistically significant. Similarly, probing depth (r = 0.73),
      plaque (r = 0.07) and tooth mobility (r = 0.66) showed clear, positive
      relationships with oral malodor.

PMID- 9586534
TI  - Efficacy of chewing gum in preventing extrinsic tooth staining.
AB  - The purpose of this six-week clinical study was to determine the efficacy of
      sugar-free chewing gum versus no chewing on preventing Peridex (0.12%
      chlorhexidine)-associated stain. One-hundred and fifty healthy adult subjects,
      categorized by tea or coffee intake and smoking, were randomly assigned to a
      chewing or no chewing gum group. All subjects were given Peridex and an ADA
      approved toothbrush and fluoride toothpaste to use twice a day. Gum was chewed
      for 20 minutes five times each day, after toothbrushing and Peridex rinse in the
      morning and evening, and after each meal. At baseline, all subjects received a
      professional cleaning to remove all supragingival deposits and extrinsic strain.
      At three and six weeks, safety and stain intensity and area were monitored on the
      anterior teeth and posterior Ramfjord teeth using the Lobene stain scoring
      method. Seventy-two subjects in each group completed the study. Attrition was
      unrelated to product use. No untoward reactions were reported or observed at any
      time in the study. At the six-week evaluations, the chewing gum group exhibited
      significantly lower (p < 0.05-0.001) total stain scores on both anterior and
      posterior areas evaluated compared to the no chewing group scores. In addition to
      the stain evaluations, a randomly selected subset of 60 subjects was evaluated
      for gingivitis at baseline prior to cleaning, and at three and six weeks, on the
      buccal and lingual surfaces of the Ramfjord teeth. Both the chewing gum and no
      chewing gum subset subjects had a significant decrease in gingivitis scores from
      baseline to three weeks (p < 0.001) and from baseline to six weeks (p < 0.05
      0.001). There were no significant statistical differences between the two groups
      at anytime during the study on gingivitis levels. Chewing gum, after product use,
      did not reduce the efficacy of chlorhexidine on gingivitis scores.

PMID- 9586536
TI  - Distraction osteogenesis and its application to the midface and bony orbit in
      craniosynostosis syndromes.
AB  - The purpose of this study was to demonstrate the potential advantages of applying
      distraction osteogenesis techniques to the correction of orbital and midfacial
      hypoplasia in craniosynostosis syndromes. Fifteen children with various
      craniosynostosis syndromes underwent Le Fort III advancement assisted by gradual
      distraction utilizing a pair of internal distraction devices custom-fabricated
      for each child. The surgical procedure consisted of a Le Fort III osteotomy,
      implantation of internal devices with initiation of distraction intraoperatively,
      and an accelerated rate of midfacial advancement over the next 3 to 5 days.
      Activation of the distraction hardware was accomplished by a percutaneous pin,
      which was removed at the end of the distraction protocol, allowing the internal
      devices to fixate the fragment for a minimum of 6 months during the period of
      consolidation. With follow-up ranging between 3 to 38 months, the average orbital
      and midfacial advancement was 19.7 mm (range, 12.0-30.0 mm). Proptosis was
      lessened and facial proportions significantly improved in all patients. Serious
      complications were not encountered. The modified distraction protocol utilized in
      this group of patients was aimed at addressing the unique requirements of
      pediatric craniofacial surgery, and resulted in almost twice the amount of
      correction previously reported for traditional rigid fixation techniques.

PMID- 9586535
TI  - The effect of bicarbonate/fluoride dentifrices on human plaque pH.
AB  - The acidogenic response in dental plaque after rinsing with sodium
      bicarbonate/fluoride dentifrice slurries was studied using three intra-oral
      models. In the first model, resting plaque pH was monitored in mesiobuccal plaque
      on upper molars and premolars in six healthy subjects after abstinence from
      normal oral hygiene for three days. These measurements were followed by a three
      minute rinse with 10% sucrose and, following a two-minute interval, a three
      minute rinse with a test dentifrice slurry. After the test dentifrice rinse, pH
      was monitored at regular intervals up to 60 minutes. Flow rate, pH and buffer
      capacity of stimulated saliva were also determined. Changes in resting pH, plaque
      pH minima, and maximum pH drop were calculated. A clear elevation in the resting
      pH was observed after bicarbonate/fluoride dentifrice rinses, and a significant
      increase was obtained in the pH minima. The smallest pH drop also was found after
      treatment with the bicarbonate/fluoride dentifrice rinse treatment (p < 0.02). A
      second model using telemetric partial dentures with interproximally placed micro
      antimony pH electrodes was used to study the effects of rinsing with increasing
      concentrations of sodium bicarbonate and calcium carbonate solutions, and with a
      fluoride dentifrice containing sodium bicarbonate. The response to these
      treatments was found to be rapid, dose-dependent, and was the greatest from the
      sodium bicarbonate. A third model used 24 subjects to assess the effects of
      sodium bicarbonate/fluoride dentifrice on plaque pH before and after a glucose
      challenge. The use of the bicarbonate/fluoride dentifrice resulted in
      significantly less measurable plaque acid than the fluoride dentifrice treatment.
      Collectively, these results indicate bicarbonate in dentifrice to be an effective
      buffering agent for stabilizing the pH and neutralizing plaque acids in dental
      plaque.

PMID- 9586539
TI  - Oral-acral syndrome and its correction using maxillary bone distraction
      osteogenesis.
AB  - A rare congenital defect of the anterior part of the maxillary bone and absence
      of teeth is presented. We describe a patient with oral-acral syndrome and the
      treatment of the maxillary retrusion using distraction osteogenesis.

PMID- 9586537
TI  - Midfacial advancement by bone distraction for treatment of craniofacial
      deformities.
AB  - Craniofaciostenosis is often associated with midfacial hypoplasia and has been
      treated traditionally using Le Fort advancement osteotomies and bone grafts. The
      surgical procedure requires a prolonged operating time, several osteotomies with
      a significant blood loss, and wide surgical exposure. According to the principles
      of bone lengthening, we performed midfacial advancement by bone distraction in 4
      patients with midfacial hypoplasia to reduce the operative time and complication
      rate. In 2 patients with Crouzon's syndrome we performed a Le Fort III osteotomy
      and placed the distraction device behind the malar eminence and screwed it on the
      temporal bone bilaterally. In the other 2 children, with Apert's syndrome, we
      performed frontal advancement and remodeling before placing the device during the
      same surgery behind the malar bone without any midfacial osteotomy. It appears to
      us that patients with more severe deformities will need surgical procedures to
      offer more satisfactory results. In these patients, distraction is an initial
      therapy to reduce the severity of the deformity, making it possible to effect a
      better treatment afterward.

PMID- 9586540
TI  - Mandibular distraction in glossoptosis-micrognathic association: preliminary
      report.
AB  - Surgical treatment for glossoptosis-micrognathic association is indicated in the
      most severe cases. Usually, complications occur. We used mandibular distraction
      to pull the tongue away from the posterior pharyngeal wall. This procedure, used
      in 3 patients, was effective.

PMID- 9586541
TI  - Radiation-induced impairment of bone healing can be overcome by recombinant human
      bone morphogenetic protein-2.
AB  - Radiotherapy of head and neck tumors very often results in impaired healing of
      craniomaxillofacial bones in the vicinity. Management of radionecrosis of bones
      after radiotherapy is an important clinical challenge. Bone morphogenetic
      proteins (BMPs) induce new bone differentiation. The aim of this study is to
      investigate the potential of BMPs in ameliorating radiation-induced impaired bone
      repair. Two 3-mm diameter defects were created in the calvaria of rats. The
      defects were treated with different doses of recombinant human (rh) BMP-2 using
      collagen type I as a carrier. Irradiation with a single dose of 1,200 rad was
      performed 2 or 7 days preoperatively. Unirradiated animals served as controls.
      New bone formation was assessed by quantitation of radiographs of the calvaria
      and histology on day 21 after surgery. Untreated, unirradiated defects showed a
      spontaneous osseous regeneration of 90 +/- 7% of the defect area within 21 days.
      Irradiation of the site (1,200 rad 2 days preoperatively) resulted in a profound
      decrease in the bone fill of the untreated defect (5 +/- 2%). Recombinant human
      BMP-2 in soluble collagen type I carrier delivered to the defect resulted in a
      significant increase of new bone formation (34 +/- 14%, P < 0.01 for 25
      micrograms rhBMP-2; 77 +/- 19% for 35 micrograms rhBMP-2, P < 0.01). Type I
      collagen carrier alone resulted in only 7 +/- 2% healing. In conclusion,
      radiation-induced impairment of calvarial repair can be overcome by rhBMP-2.
      Thus, the concept of BMP-2-induced regeneration has potential applications in
      reconstructive craniomaxillofacial surgery after irradiation.

PMID- 9586543
TI  - Osteoinductive potential of demineralized rat bone increases with increasing
      donor age from birth to adulthood.
AB  - Demineralized allogenic bone implanted in the subcutis or muscle of rodents
      causes formation of heterotopic bone by osteoinduction. The osteoinductive
      response may be weaker in primates than in rodents. It was suggested that the
      osteoinductive response of demineralized bone for clinical use could be enhanced
      by using young donors, because studies have indicated that the osteoinductive
      response is reduced in demineralized bone of old versus young donors. However,
      these findings may not represent a gradual decline in the osteoinductive property
      of bone matrix throughout the life span. We evaluated quantitatively, by uptake
      of strontium 85, the osteoinductive effect of demineralized bone matrix from
      newborn, 8-week-old (adolescent), and 8-month-old (adult) male Wistar rats
      implanted in the abdominal muscles of 8-week-old male Wistar rats. The
      osteoinductive response increased significantly with increasing donor age. The
      results of the present study, weighed with those of previous studies, indicate
      that the osteogenic potential of the bone matrix increases from newborn to
      adulthood but decreases in the aged rat. This may be due to changes in
      concentration of essential growth factors (e.g., bone morphogenetic proteins)
      resulting from maturational changes from birth to adulthood and osteoporotic
      changes occurring in later years. The results do not support the contention that
      young donors of demineralized bone are preferable to adult donors.

PMID- 9586542
TI  - Effect of insulin-like growth factor type I on critical size calvarial bone
      defects in irradiated rats.
AB  - Irradiated wounds are characterized by a slow healing process. Insulin-like
      growth factor-1 (IGF-1), a somatomedin C, has been shown in previous studies to
      stimulate collagen synthesis and bony repair. The purpose of this investigation
      is to evaluate the potential beneficial effects of recombinant IGF-1 in the
      healing of critical size calvarial defects in previously irradiated adult male
      Sprague-Dawley rats.

PMID- 9586544
TI  - Two lyophilized polymer matrix recombinant human bone morphogenetic protein-2
      carriers in rabbit calvarial defects.
AB  - We have developed a lyophilized bone morphogenetic protein (BMP) delivery device
      that can be formulated to control release over 2 to 8 weeks. Bioerodible poly
      (d,l lactide-co-glycolide) particles loaded with 90 micrograms recombinant human
      BMP-2 were suspended in either carboxymethylcellulose (CMC) or methylcellulose
      (MC) implants. Plain CMC and MC implants served as controls, as did a
      nonimplanted group. A total of 40 rabbits was evaluated histologically 2, 4, or 8
      weeks after receiving circular full-thickness 15-mm calvarial defects. MC
      appeared to prevent prolapse of periosteum and dura into the defects and did not
      elicit bone growth. Addition of BMP improved the result. CMC implants appeared to
      encourage bone growth even in the absence of BMP. When BMP was added, new bone
      formed earlier. CMC may influence new bone formation because it is hydrophilic.
      MC is less hydrophilic and may cause undue inflammation. Either can be combined
      with BMP to produce unitary devices that are easy to make and use.

PMID- 9586545
TI  - Endoscopic dissection of dura and craniotomy with minimal trephines: a
      preliminary series.
AB  - The first nine clinical cases using endoscopic dissection of dura and craniotomy
      with minimal trephines were performed from June to August 1997 after trial
      dissection of 19 fresh cadavers conducted at the University of Brno's Pathology
      Institute in the Czech Republic. These procedures involved the refinement of
      craniofacial and intracranial surgical techniques using the endoscope and
      prototype instruments. These dissections demonstrated that intracranial
      structures can be explored using an endoscope without encumbrance, and that major
      craniofacial surgeries may also be performed with minor incisions and minimal
      craniotomies. Furthermore, we seek to illustrate that use of the endoscope in
      craniofacial surgery provides improved visualization and protection of vital
      structures while simultaneously allowing the surgeon to perform delicate
      maneuvers. This permits minimal brain retraction with less subsequent morbidity.
      This minimally invasive craniofacial-intracranial surgical technique using the
      endoscope is performed with minimal cutaneous incisions, avoiding wide exposure
      of subcutaneous tissue, cranium, and meningeal structures. The ultimate goal is
      to perform endoscopic intracranial osteotomies and obtain advancement of
      craniofacial skeleton with gradual distraction. Potential neurosurgical
      advantages include improved postoperative recovery, decreased cerebral edema, and
      decreased risk of hemorrhage and infection.

PMID- 9586546
TI  - Mutations in fibroblast growth factor receptor 2 gene and craniosynostotic
      syndromes in Japanese children.
AB  - We examined the gene mutations of fibroblast growth factor receptor 2 (FGFR2) in
      Japanese syndromic craniosynostotic patients. Subjects included 1 patient with
      Apert's syndrome, 1 patient with Crouzon's syndrome, and 3 patients with
      Pfeiffer's syndrome, as well as two control patients. The genomic
      deoxyribonucleic acid of each patient was extracted, and the mutation sites of
      the FGFR2 gene were amplified and sequenced. One patient with Apert's syndrome
      showed a FGFR2 mutation of S252W (TCG-->TGG), 1 patient with Crouzon's syndrome
      had a mutation of C342W (TGC-->TGG), and the 3 patients with Pfeiffer's syndrome
      had mutations of T341P (ACG-->CCG), C342S (TGC-->TCC), and D321A (GAC-->GCC). The
      role of FGF families and the effect of FGFR2 mutations on craniofacial
      morphogenesis are discussed.

PMID- 9586547
TI  - Intraosseous plating: a new method for biodegradable osteofixation in
      craniofacial surgery.
AB  - Biodegradable miniplates and screws offer special possibilities for surgical
      techniques because the removal operation is avoided. In areas beneath thin skin,
      intraosseous plating could be preferable to avoid palpability and transient
      swelling during resorption. The tissue reaction to a 0.5-mm-thick self-reinforced
      poly-L-lactide (SR-PLLA) plate fixed with an SR-PLLA miniscrew was studied
      histologically and histomorphometrically after implantation into the calvarium of
      six young sheep. After follow-up periods of 6, 20, and 52 weeks, no signs of
      adverse tissue reaction such as clinically manifest foreign body reaction or
      histologically manifest osteolysis were noted. By 52 weeks the implants were
      largely in direct contact with remodeled, dense bone tissue. No signs of
      fragmentation or resorption were noted in the intraosseous parts of the implants,
      whereas the screw head had been fragmented and was undergoing resorption at 52
      weeks. The screw head is unnecessary in this plating method and could have been
      removed with a hot wire loop. The excellent biocompatibility of the mechanically
      strong, resorbable SR-PLLA plate with miniscrew fixation provides a possibility
      for intraosseous plating in less loaded craniofacial areas, especially in areas
      with very thin soft-tissue coverage.

PMID- 9586548
TI  - Speech changes after maxillary advancement in 40 cleft lip and palate patients.
AB  - In this study, we retrospectively investigated speech intelligibility changes in
      40 patients at the Australian Cranio-Facial Unit who underwent Le Fort I
      maxillary advancement between 1978 and 1995. Resonance, articulation, and
      velopharyngeal sphincteric function, which were assessed before and after
      surgery, were analyzed in conjunction with details of the surgery in an attempt
      to identify the factors affecting speech intelligibility. Of the 40 patients, 10
      experienced improved speech (improved intelligibility group), 18 demonstrated no
      detectable changes in speech (unchanged intelligibility group), and 12 presented
      with worsened speech intelligibility (deteriorated intelligibility group). The
      average amount of advancement was 9.4 mm in the improved and unchanged
      intelligibility groups and 12.2 mm in the deteriorated intelligibility group.
      There was a statistically significant difference in the average amount of
      advancement between the improved and unchanged groups and the deteriorated
      intelligibility group. In the improved intelligibility group, 9 patients
      demonstrated improved articulation and 7 had reduced hyponasality. Conversely, in
      the deteriorated intelligibility group, 10 patients demonstrated increased
      hypernasality. Intelligibility ratings appeared to depend on the balance between
      the benefits of amelioration of hyponasality and misarticulations and the debit
      of increased hypernasality. The amount of maxillary advancement has a direct
      bearing on speech intelligibility. The amelioration of speech intelligibility
      improves if the amelioration of distorted articulation and hyponasality overrides
      any increase in hypernasality.

PMID- 9586549
TI  - Innervation pattern of the temporalis muscle.
AB  - The purpose of this article is to describe the neural anatomy of the temporalis
      muscle as dissected along the intramuscular temporal fascial plane. This sagittal
      plane is a natural cleavage plane of the muscle, which is explored along with its
      relationship to the deep temporal nerve. Eight temporalis muscle specimens were
      removed in their entirety from 8 preserved cadavers. The muscles were selected
      based on whether they were grossly intact prior to procurement for processing.
      The muscle specimens were then processed over a 3-month period using Sihler's
      staining technique. Muscle dissection was performed along the intramuscular
      fascial plane under an operating microscope, taking care to preserve the
      underlying nerve and arterial anatomy. Dissections demonstrated an anterior and
      posterior division of the deep temporal nerve running within the deep portion of
      the muscle below the intramuscular fascial plane. This fascial layer provided a
      natural dissection plane to expose and evaluate the underlying nerve and arterial
      anatomy. In all specimens the deep temporal artery originated with the anterior
      temporal nerve and then branched into an anterior and posterior division. The
      innervation density and nerve caliber of the anterior portion of the muscle was
      much greater than that of the posterior, correlating with a greater anterior
      muscle bulk. This may have implications in differences in fiber type and
      functional regionalization of the muscle. The results of this anatomic study
      support the finding of an anterior and posterior division of the deep temporal
      nerve within the deep portion of the temporalis muscle. In addition, differences
      in the innervation density and muscle bulk lend credence to the possibility of
      regional muscle specialization. The natural cleavage plane of the intramuscular
      temporal fascia may have clinical ramifications for temporalis myofascial flaps
      while preserving the underlying neural anatomy to allow for normal residual
      temporalis muscle function.

PMID- 9586550
TI  - Prenatal diagnosis: evolution in craniofacial surgery.
AB  - Prenatal diagnosis of craniomaxillofacial malformations permits early surgery,
      before 6 months of life and possibly, in the near future, in utero, thereby
      obtaining the best aesthetic and functional results. Increased knowledge of
      embryology has largely improved the diagnosis of craniomaxillofacial anomalies,
      their classification, and therapeutic protocols. We analyzed nine pregnancies
      (one twin) in which cleft lip and palate (CLP)--isolated or associated with, for
      example, holoprosencephaly, hypertelorism, and micrognathia--was diagnosed by
      ultrasonography. Only one fetus of these pregnancies was later operated on in our
      unit. This patient, with 7 years follow-up, represents our clinical case. For
      these cases, early diagnosis of CLP allowed informed parental choice regarding
      the continuation or termination of the affected pregnancy and planning of
      surgical procedures to correct the malformation. This is demonstrated by the
      presented clinical case involving an infant operated on within 6 months with
      success.

PMID- 9586551
TI  - Electrical discharge machining.
AB  - This article describes a laboratory technique of achieving the highest degree of
      passive fit of an implant-retained restoration using electric discharge machining
      (EDM). This process can save time by eliminating the need for conventional
      soldering procedures, increase the longevity of the restoration, and when used
      along with the clinical technique of fabricating a verification index, eliminate
      the clinical try-in phase.

PMID- 9586552
TI  - Communication is vital to produce natural looking metal ceramic crowns.
AB  - Many in the dental profession believe that accurate shade matching of the single
      anterior tooth is impossible. Fabricating an anterior porcelain crown to
      accurately match surrounding teeth is the most difficult task in our industry.
      However, it is not impossible. For many years, I took custom shades for a large
      dental group, and while there were many successes, there were also many failures.
      In one incident, the dentist, his team and I all agreed on a Vita Lumin A-2 for a
      patient. I attended the try-in. To everyone's surprise, the crown did not match
      the patient's natural teeth. After taking a new shade and delivering the new
      crown, the shade matched more closely, but still "no cigar." This particular
      failure resulted in the loss of a patient. Unfortunately, this was one of several
      incidents involving a mismatched shade and unsatisfied patient. These experiences
      caused me to question the techniques I was using. From them, I developed a
      technique for taking shades which could be shared with others to eliminate the
      frustrations we have all encountered.

PMID- 9586553
TI  - Laboratory lotto? Are you gambling with your success?

PMID- 9586554
TI  - The challenges of dental laboratory technology education: will it survive?
AB  - Accredited formal educational programs in dental laboratory technology are now
      under pressures at levels they have never undergone before. Already pushed to the
      point where many have had to close their doors, the remainder are struggling to
      survive with already strained resources. Whether or not they will be able to
      maintain their existence will depend upon their ability to attract quality
      students, provide them with a good, up to date education, and do so with ever
      increasing efficiency.

PMID- 9586555
TI  - Taking posterior restorations to the next level: a new way to communicate
      occlusal color and characterization.

PMID- 9586556
TI  - Single implant tooth replacement.
AB  - It has been shown that direct bone anchorage of dental implants will provide long
      term predictability for single tooth implants and multi-unit implants. The
      function of implant-supported restoration is now routinely achieved. The real
      challenge facing the restorative dentist and laboratory technician is to achieve
      optimal aesthetics. The learning objective of this article is to review the
      prosthodontic procedures essential to maximizing natural aesthetics in implant
      supported restorations. It will provide a review of master impression techniques,
      prepable titanium abutments and designing the cement on restoration. Particular
      emphasis is directed to the soft tissue model from which a series of sequenced
      techniques can be followed to achieve optimal aesthetics. Analysis of the implant
      alignment with regard to the neighboring teeth will result in having to make a
      choice of which prepable abutment will maximize the aesthetic result. The
      following case outlines how to replace a single missing tooth using an externally
      hexed implant system and a prefabricated titanium abutment on a 26-year-old male
      patient.

PMID- 9586557
TI  - Comparing vertical dimension changes with and without a face-bow transfer.
AB  - The purpose of this investigation was to identify any difference of vertical
      dimension change that could be attributed to not using a face-bow transfer. Both
      demonstrations resulted in occlusal changes in vertical dimension. In comparing
      the demonstrations, where a hinge axis transfer was not taken, a greater amount
      of change was recorded over that observer in the demonstration where the hinge
      axis transfer was made. More dedicated research is clearly warranted to establish
      how much of the change was due to normal technical error. The time spent taking a
      face-bow transfer (hinge axis) may represent a small portion of the time required
      to accomplish adjustments on a denture where no transfer was performed. This
      information will allow the clinician to decide on the time they are willing to
      dedicate to occlusal corrections at the chair.

PMID- 9586559
TI  - New ZAAG Implant Attachment brochure from Zest Anchors.

PMID- 9586558
TI  - B.S. Education in Dental Laboratory Sciences at the University of Texas Health
      Science Center: an organizing framework.
AB  - This article describes the conceptual framework upon which the Bachelor's Degree
      program in Dental Laboratory Sciences at the University of Texas Health Science
      Center was constructed. Development of specific program objectives rested on the
      following four guiding principles: 1) combine professional laboratory training
      with management education; 2) focus on a problem-based pedagogy; 3) provide
      flexibility to accommodate today's "nontraditional" student population; and 4)
      utilize the close relationship with the University of Texas Dental School at San
      Antonio.

PMID- 9586560
TI  - Interview with Professor Per-Ingvar Branemark. Interview by Gregory J. Boyajian.

PMID- 9586562
TI  - Providing tongue comfort in removable partial dentures.

PMID- 9586561
TI  - Montreal bar: in search of the positive fit.

PMID- 9586563
TI  - Use of hemoglobin as an iron source by Bacillus cereus.
AB  - The hemoglobin binding activity of Bacillus cereus cells was measured with
      fluoresceinisothiocyanate (FITC)-conjugated hemoglobin using flow cytometry.
      Growth of B. cereus was markedly inhibited by the addition of apo-transferrin. B.
      cereus could not use transferrin-bound iron as an iron source in serum. The
      growth inhibition was reversed by the addition of a FeCl3 solution, erythrocytes
      or hemoglobin. B. cereus released hemolysin; these findings suggested that the
      hemoglobin released from erythrocytes by B. cereus hemolysin binds to B. cereus
      and is thus used as an iron source.

PMID- 9586564
TI  - Inhibitory effect of calcium-binding protein regucalcin on protein kinase C
      activity in rat renal cortex cytosol.
AB  - The effect of regucalcin, a calcium-binding protein, on Ca2+-and phospholipid
      dependent protein kinase (protein kinase C) activity in the cytosol of rat kidney
      cortex was investigated. With increasing concentrations of Ca2+,
      phosphatidylserine or dioctanoylglycerol in the reaction mixture, regucalcin (10[
      8] M) caused a remarkable inhibition of protein kinase C activity. Regucalcin did
      not have a significant effect on protein kinase C activity in the presence of
      phosphatidylserine or dioctanoylglycerol without Ca2+ addition. Moreover,
      regucalcin significantly inhibited phorbol 12-myristate 13-acetate (PMA)
      increased protein kinase C activity. Meanwhile, staurosporine (10[-9] M) caused a
      significant inhibition of protein kinase C activity. This inhibition was further
      enhanced by regucalcin addition. Regucalcin itself did not have protein kinase
      activity in either the presence or the absence of both Ca2+ and phospholipids.
      These results clearly indicate that regucalcin has an inhibitory effect on
      protein kinase C activity in the cytosol of rat kidney cortex. This inhibitory
      effect may be partly due to the regucalcin-induced Ca2+ binding.

PMID- 9586565
TI  - Blue fluorescence generated during lipid oxidation of rat liver microsomes cannot
      be derived from malonaldehyde but can be from other aldehyde species.
AB  - Generation of blue fluorescence together with phospholipid hydroperoxides and
      aldehyde species in rat liver microsomes during oxidation with FeCl2-ADP-ascorbic
      acid was monitored, and the kind of lipid oxidation products participating in the
      formation of blue fluorescence was investigated. Contents of phospholipid
      hydroperoxides were increased in an early stage of oxidation, and were decreased
      in an advanced stage of oxidation. Contents of components that liberated
      malonaldehyde, 4-hydroxyalkenals and other unsaturated aldehydes under the acidic
      assay conditions were increased in the advanced stage of oxidation. Water-soluble
      blue fluorescence with a maximum at 440-450 nm determined after separation
      through gel filtration accumulated in the advanced stage of oxidation, and was
      characterized as resistant to borohydride treatment and to be little dependent on
      pH values of the solvent. Wavelength of the maximum fluorescence and
      characteristics of the fluorescence were similar to those of fluorescence with
      maxima at 440-450 nm formed by reaction of unoxidized microsomes, bovine serum
      albumin or methylamine with alkenals, and different from those of fluorescence
      with maxima at above 460 nm obtained by the reaction with a mixture containing
      malonaldehyde. Hence, blue fluorescence accumulated in oxidized microsomes cannot
      be derived from free malonaldehyde but can be from other aldehyde species
      including alkenals.

PMID- 9586566
TI  - Isolation and characterization of two plasmids that mediate macrolide resistance
      in Escherichia coli: transferability and molecular properties.
AB  - Escherichia coli BM2506 is highly resistant to macrolide antibiotics; it produces
      macrolide 2'-phosphotransferase II [MPH(2')II] which inactivates such drugs. We
      investigated the localization and the transfer of the macrolide-resistance
      determinant that encoded the mphB gene for MPH(2')II in strain BM2506. Although
      we detected no clear band of plasmid DNA after agarose gel electrophoresis,
      transformation analysis using satellite DNA that corresponded to plasmid DNA
      after CsCl-ethidium bromide gradient centrifugation and restriction analysis of
      plasmid DNA in transformants showed that strain BM2506 harbored two plasmids,
      pTZ3721 (84 kb) and pTZ3723 (24 kb), that specified resistance to macrolides,
      ampicillin, streptomycin, tetracycline and sulfonamide and to macrolides and
      ampicillin, respectively. Southern hybridization showed that the mphB gene
      hybridized to both plasmids. Furthermore, pTZ3721 was transferred by conjugation
      to another strain of E. coli and pTZ3723 was mobilized with a self-transferable
      plasmid RP1 to other strains of E. coli. Therefore, it appears that the mphB gene
      is located on two plasmids in BM2506 and can be transferred to other strains of
      E. coli by conjugation or mobilization.

PMID- 9586567
TI  - Non-antigenic and low allergic gelatin produced by specific digestion with an
      enzyme-coupled matrix.
AB  - Porcine gelatin (heat-denatured collagen) was digested with a bioreactor using an
      enzyme-coupled matrix (ECM) with purified collagenase. The digested gelatin,
      FreAlagin type R (M.W. range 200-10000 Da), was further purified by an HPLC
      system depending upon molecular size. The molecular weight range of the purified
      fractions, FreAlagin type P and type AD, were 200-500 and 2000-10000 Da,
      respectively, and glycine was the N-terminal amino acid of both types (> or
      =93%). ECM has the capability of digesting gelatin at a specific point in the
      sequence before glycine, and it was determined that FreAlagin type P consists of
      a tri-peptide fraction with the amino acid sequence Gly-X-Y. No types of
      FreAlagin exhibited any reactivity with gelatin-specific IgG antibody raised in
      guinea pigs, and they also possessed an extremely low reactivity with gelatin
      specific IgE antibody from the sera of patients who had experienced an
      anaphylactic reaction against gelatin after vaccination or after eating gelatin
      containing foods. From these results, it was determined that FreAlagin types R
      and AD were non-antigenic, low-allergic gelatins. FreAlagin type R, and
      especially type AD, had strong adsorption-blocking activity comparable to the
      level of bovine serum albumin, whereas type P and glycine had virtually no
      adsorption-blocking activity. Therefore, the new types of gelatin, FreAlagin
      types R and AD, are suitable for pharmaceutical use to avoid gelatin allergy.

PMID- 9586568
TI  - Gastric cytoprotective activity of dehydroleucodine in rats. Role of
      prostaglandins.
AB  - Previously, we reported that dehydroleucodine (DhL), a sesquiterpene lactone,
      protected the gastric mucosa of rats from absolute ethanol-induced lesions in a
      dose-dependent fashion. The mechanism is not mediated by an antiacid secretory
      action and DhL stimulated mucous production. In the present study, we report the
      effect of DhL on the mucosal production of prostaglandin E (PGE) and the mucosal
      release of PGE2 in rats stomach. DhL in acute treatment does not modify these
      values decreased by previous treatment with indomethacin or absolute ethanol.
      However, DhL in subchronic treatment significantly enhanced the mucosal
      production of PGE and the mucosal release of PGE2. Also, indomethacin
      pretreatment resulted in a significant reduction of the cytoprotective action of
      DhL. These results indicate the participation of endogenous prostaglandins in DhL
      protection against ethanol damage. Moreover, we suggest that the gastric
      protective activity of DhL against ethanol induced gastric mucosal damage is
      mediated, at least in part, through PGE and PGE2 in subchronic treatment.

PMID- 9586569
TI  - Augmentation of tumor immunity in mice by intralesional injection of vitamin A.
AB  - We investigated the antitumor effect of vitamin A(VA) using the double grafted
      tumor technique to examine whether VA administered into a primary tumor
      (intralesionally or i.l.) accelerates antitumor immune reactions so that growth
      of the secondary tumor may be more effectively inhibited than by other systemic
      administration routes. In the double grafted tumor system, where BALB/c mice were
      inoculated with MethA fibrosarcoma cells into the right inguinal region (1 x
      10[6] cells) on day 0 and later into the left (3 x 10[6] cells) on day 10, the
      injection of VA at a dose of 1000 IU/mouse i.l., s.c., i.p., and i.v. on days 3
      through 7 inhibited the growth of the secondary tumor to the same extent, while
      VA at the i.l. dose of 100 IU/mouse into the primary tumor inhibited more
      effectively than by any other administration route. VA did not inhibit the
      secondary MethA growth in BALB/c (nu/nu) mice. The spleen cells taken from VA
      treated tumor-bearing mice prevented the growth of MethA tumors in naive BALB/c
      mice when given as a mixture with the MethA inoculum (the Winn assay). The
      delayed-type hypersensitivity (DTH) response to methylated bovine serum albumin
      (MBSA) antigen was augmented when VA (1000 IU) was injected at the site of the
      antigen injection. These results suggest that the direct interaction of VA with
      the tumor cells may be necessary for the tumor immunity-potentiating effect of
      VA, and that T-lymphocyte-mediated tumor immunity is involved in the anti-tumor
      effect of VA. The antitumor mechanism of VA seems to involve retinoid receptors,
      because the benzoic acid derivative Am80, which has been reported to exert
      retinoidal activity by binding to specific retinoid receptors, also showed
      activity.

PMID- 9586570
TI  - Inhibitory effects of tetrandrine on angiogenesis in adjuvant-induced chronic
      inflammation and tube formation of vascular endothelial cells.
AB  - The inhibitory effects of tetrandrine (an alkaloid isolated from the Chinese
      medicine Stephania tetrandrae S. Moore) were investigated in terms of the
      angiogenesis in an adjuvant-induced chronic inflammation model of mouse and tube
      formation of rat vascular endothelial cells (EC). Tetrandrine (7.5-30 mg/kg)
      reduced the carmine content, granuloma weight, inflammatory cell count and pouch
      fluid weight in the inflammation model in a dose-dependent manner. The inhibitory
      pattern of tetrandrine on these parameters was similar to that of hydrocortisone.
      The inhibitory effect of tetrandrine on carmine content was 0.56-fold smaller
      than that of hydrocortisone. Tetrandrine (0.1-10 microM) also inhibited 2% fetal
      bovine serum (FBS)-stimulated tube formation of vascular EC. The inhibitory
      effect of tetrandrine on tube formation was more than 100-fold greater than that
      of hydrocortisone. Tetrandrine (10-30 nM) inhibited the tube formation stimulated
      by interleukin (IL)-1alpha and platelet-derived growth factor (PDGF)-BB to a
      greater extent than FBS-stimulated tube formation. The inhibitory effects of
      tetrandrine on the action of IL-1alpha and PDGF-BB were non-competitive. These
      results demonstrate that tetrandrine may reduce the tube formation of EC in the
      angiogenic process through inhibition on the post-receptor pathway of IL-1alpha
      and PDGF-BB in chronic inflammation.

PMID- 9586571
TI  - Pharmacological characterization of a novel long-acting histamine H1 receptor
      antagonist, KAA-276.
AB  - The pharmacological profile of a newly synthesized histamine H1 receptor
      antagonist, KAA-276 (1-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-yl]-5-12-[4-(
      2-carboxyethyl)-phenyl]ethyl]-1,5-diazacyclooctane sulfate), was characterized.
      In a H1 receptor binding assay in vitro, KAA-276 inhibited [3H]mepyramine binding
      to guinea pig cerebellar membrane preparations with an IC50 of 0.66 nM. The
      inhibitory potency of KAA-276 was greater than that of terfenadine, but similar
      to that of astemizole and ketotifen. KAA-276 antagonized the histamine-induced
      constriction of ileum and trachea isolated from guinea pigs in a dose-dependent
      manner with a concomitant reduction in the maximum response. Furthermore, the
      inhibitory effect of KAA-276 on histamine induced contraction was potentiated
      depending on the duration of preincubation time and revealed an irreversible
      property. KAA-276 given orally, intraduodenally, and by inhalation significantly
      inhibited histamine-induced bronchoconstriction dose-dependently in guinea pigs.
      Inhalation of KAA-276 exhibited inhibitory activity with a rapid onset and long
      duration, while intraduodenal administration resulted in action with a slow
      onset. Therefore, KAA-276, an irreversible and selective histamine H1 receptor
      antagonist, was shown to be a useful drug for therapeutic strategies against
      bronchial asthma when administered by the aerosol route.

PMID- 9586572
TI  - Structure-activity relationships of alkylxanthine inhibitors of phosphodiesterase
      IV isoenzyme.
AB  - The structural and electronic properties of seventeen alkylxanthine derivatives
      were calculated using the MO program PM3 to elucidate the key features related to
      their inhibitory activity on phosphodiesterase (PDE) IV isoenzyme. Except for 7
      alkylxanthine derivatives, a good correlation could be established between the
      distance between the tops of the two alkyl groups at the N1 and N3 positions of
      the xanthine skeleton (molecular length) and the PDE IV inhibitory activity
      (r=0.973, n=13). The same inhibitory activity could also be significantly
      correlated with the following electronic parameters of alkylxanthines: HOMO
      energy (r=0.850), absolute hardness (r=-0.806), and absolute electronegativity
      (r=-0.825). These results suggest that the electronic properties are partly
      responsible for PDE IV inhibition as far as the effects of structural properties
      associated with molecular length are concerned. Alkylxanthines may also act as
      electron donors in the charge-transfer interaction with the active sites on PDE
      IV isoenzyme.

PMID- 9586573
TI  - Metabolism of kalopanaxsaponin B and H by human intestinal bacteria and
      antidiabetic activity of their metabolites.
AB  - To investigate the relationship between the intestinal bacterial metabolism of
      kalopanaxsaponin B and H from Kalopanax pictus (Araliaceae), and their
      antidiabetic effect, kalopanaxsaponin B and H were metabolized by human
      intestinal microflora and the antidiabetic activity of their metabolites was
      measured. Human intestinal microflora metabolized kalopanaxsaponin B to
      kalopanaxsaponin A, hederagenin 3-O-alpha-L-arabinopyranoside and hederagenin.
      The main metabolites of kalopanaxsaponin B were kalopanaxsaponin A and
      hederagenin. Kalopanaxsaponin H was metabolized to kalopanaxsaponin A and I,
      hederagenin 3-O-alpha-L-arabinopyranoside and hederagenin. The main metabolites
      of kalopanaxsaponin H were kalopanaxsaponin I and hederagenin. Among
      kalopanaxsaponin B, H and their metabolites, kalopanaxsaponin A showed the most
      potent antidiabetic activity, followed by hederagenin. However, the main
      components, kalopanaxsaponin B and H, in K. pictus were inactive.

PMID- 9586574
TI  - Study of the accelerating effect of shikonin and alkannin on the proliferation of
      granulation tissue in rats.
AB  - The present study was carried out to compare the accelerating effect of shikonin
      and alkannin and to elucidate the expression of CD antigen and histological
      changes on the proliferation of granulation tissue in rats. Shikonin and alkannin
      produced a dose-dependent acceleration of the cotton pellet-induced granuloma
      formation and this accelerating potency of both compounds on the proliferation of
      granulation tissue was about the same 5 and 10 d after implantation of the cotton
      pellet. Also, both compounds increased the ratio of CD11b+ cells in the
      granulation tissue 5 and 10 d after implantation of the cotton pellet. Both
      compounds increased the expression of CD11b+ cells with granulocytes such as
      macrophages and histiocytes, and then accelerated the proliferation of
      fibroblasts and collagen fiber. On the other hand, neither compound increased the
      ratio of CD3+ cells in the granulation tissue after 5 and 10 d. These results
      suggest that shikonin and alkannin accelerate the proliferation of granulation
      tissue induced by the cotton pellet and this accelerating effect may be
      attributed to an increase in the expression of CD11b+ cells, and the acceleration
      of the proliferation of fibroblasts and collagen fiber in the granulation tissue.

PMID- 9586575
TI  - Inhibitory effect of diarylheptanoids on nitric oxide production in activated
      murine macrophages.
AB  - Thirteen novel diarylheptanoids bearing a chalcone or a flavanone moiety (1-13),
      a new curcumin derivative, 1,2-dihydrobis(de-O-methyl)curcumin (14), and two
      known flavonoids (15 and 16) isolated from the seeds of Alpinia blepharocalyx K.
      Schum. were tested for their inhibitory effects on nitric oxide (NO) production
      in lipopolysaccaride (LPS)-activated murine macrophages J774.1 in vitro. All the
      tested compounds inhibited NO production in a concentration-dependent manner
      (IC50=36-568 microM). Among the compounds examined, blepharocalyxin B (13) was
      the most potent inhibitor of NO production (IC50=36 microM). Analysis of the
      structure activity relationship among these novel diarylheptanoids led to the
      conclusion that the position of attachment of a chalcone or a flavanone to a
      diarylheptanoid does not affect their inhibitory potency although their presence
      in association causes a substantial enhancement of the inhibitory activity.
      Moreover, a conjugated double bond in a chalcone moiety potentiated the
      inhibitory activity. On the other hand, hexamethoxydeoxycalyxin A (17) and
      pentamethoxycalyxin B (18), a methylated product of calyxin A (1) and an epimeric
      mixture of calyxin B, showed greatly reduced activity suggesting that phenolic
      hydroxyl groups are involved in the inhibitory activity.

PMID- 9586576
TI  - Increased anticoagulant activity of recombinant thrombomodulin modified with
      glycosaminoglycan.
AB  - Thrombomodulin (TM) is a thrombin receptor on the endothelial cell surface,
      effective as an anticoagulant by changing procoagulant thrombin to an
      anticoagulant one. As rabbit TM with glycosaminoglycan (GAG) has a more potent
      anticoagulant activity than that without GAG, we expressed recombinant GAG
      modified urinary thrombomodulin (GAG-UTM) in C-127 cells. The effect of an
      additional GAG chain on anticoagulant activity was investigated in comparison
      with unmodified recombinant UTM (r-UTM). In vitro, the activity of cleavage of
      fibrinogen by thrombin or prothrombinase activity was more potently depressed by
      GAG-UTM than by r-UTM, and the generation of activated protein C by TM-thrombin
      complex was accelerated by GAG modification. The acceleration of antithrombin III
      dependent anticoagulant activity was shown only by GAG-UTM. Parameters like
      thrombin time, prothrombin time and activated partial thromboplastin time in
      human plasma were prolonged by GAG-UTM more than by r-UTM. In vivo, the effect of
      GAG-UTM and r-UTM in endotoxin-induced disseminated intravascular coagulation
      (DIC) rats was investigated using hematological parameters. GAG-UTM and r-UTM
      significantly reduced the decrease in fibrinogen and platelet number induced by
      endotoxin at the dosage of 0.1 and 1.0 mg/kg/h, respectively, suggesting that the
      antithrombotic effect of GAG-UTM in endotoxin-induced DIC rats was 10-fold as
      potent as that of r-UTM. GAG-UTM reduced the prolongation of the bleeding time
      induced by endotoxin, while r-UTM accelerated it. These results suggest that the
      addition of a GAG chain may increase availability as an anticoagulant.

PMID- 9586578
TI  - Dose-dependent selective cytotoxicity of extracts from marine green alga,
      Cladophoropsis vaucheriaeformis, against mouse leukemia L1210 cells.
AB  - The selective cytotoxic activity of extracts from two marine green algae,
      Cladophoropsis vaucheriaeformis and Halimeda discoidea, was examined via a dose
      response assay against mouse leukemia L1210 cells and normal NIH-3T3 cells. The
      MeOH-extract from C. vaucheriaeformis showed selective cytotoxicity to L1210
      cells at concentrations ranging from 50 to 100 microg/ml. In particular, the
      greatest selectivity for cytotoxic activity was found at the concentration of 50
      microg/ml, at which the growth of L1210 cells was inhibited completely and that
      of NIH-3T3 was not affected at all. However, MeOH extracts from the red alga
      Laurencia okamurae and the brown alga Dictyopteris undulata, which displayed non
      selective cytotoxicity in our previous screening program, did not show similar
      selective cytotoxicity at any concentrations tested. These results indicate that
      the marine green alga C. vaucheriaeformis may contain a unique antitumor
      substance with selective cytotoxic activity against L1210 cells. Our results also
      suggest that this active substance might be of low molecular weight and therefore
      MeOH-soluble.

PMID- 9586577
TI  - Importance of sialic acid in recombinant thrombomodulin in terms of
      pharmacokinetics and separation of desialyzed glycoprotein.
AB  - Recombinant glycosaminoglycan-modified urinary thrombomodulin (GAG-UTM) expressed
      in mouse C-127 cells has potent antithrombotic activity available as an
      anticoagulant. GAG-UTM, a glycoprotein with sialic acid, was investigated
      regarding the influence of the terminal sialic acid on its pharmacokinetics upon
      rapid intravenous injection in rat. Asialo GAG-UTM desialated by neuraminidase
      was cleared rapidly from plasma. Sialyzed GAG-UTM, a sialyzed asialo GAG-UTM with
      alpha-2, 6-sialyltransferase, containing sialic acid similarly to native sialo
      GAG-UTM, had only a short half-life in plasma, suggesting that the binding site
      of sialic acid on galactose was not only sialyzed with alpha-2, 6
      sialyltransferase but also with 2, 3-sialyltransferase. Asialo GAG-UTM with
      oxidized terminal galactose, however, had a long half-life. These results suggest
      that terminal sialic acid may be important to the pharmacokinetics of GAG-UTM;
      therefore, an analysis of asialo GAG-UTM became significant for quality control.
      In order to analyze sialo- and asialo-types in the early stage of purification,
      we investigated separation and analysis methods for both types and found a
      suitable sample of each: RCA-120-Agarose column for separation and ELISA using
      anti-thrombomodulin antibody and RCA lectin for analysis.

PMID- 9586579
TI  - Characterization of bovine serum factor triggering the lysis of liposomes via
      complement activation.
AB  - Our previous studies have shown that the degree of damage to a liposome
      corresponds to the variability of the animal species from which the serum comes,
      and that a complement activating factor (CAF) plays an important role in inducing
      the activation of the complement system, ultimately leading to the lysis of the
      liposomes. In this study, our attention focused on the characterization of the
      bovine serum factor (bCAF) that is involved in complement-mediated immune lysis
      of the liposome. The active fraction containing CAF partially purified with PEG
      and ammonium sulfate results in marked activation of the complement system via
      the alternative pathway when interacted with CAF-depleted serum, whereas the
      active fraction or CAF-depleted serum alone does not activate the complement. The
      interaction between lipopolysaccharide (LPS), heparin, zymosan or their mixture
      in place of CAF and CAF-depleted serum does not result in any significant
      activation of the complement system. Results from pretreatment with rabbit anti
      bovine IgM IgG and rabbit anti-bovine IgG IgG indicate that activation of the
      complement system is not attributable to the antibody which is generally involved
      in activation of complement via the classical pathway. The results have further
      been proven by pretreatment with Concanavalin A (Con A) sepharose and protein G
      sepharose ruling out the possibility of antibody-mediated activation of
      complement. Our studies on collagenase and trypsin digestion demonstrate that the
      relative activity of CAF does not diminish with increase in collagenase
      concentration, and decreases with increase in trypsin concentration, strongly
      indicating that CAF does not have a collagen-like domain in its structure. The
      relative activity of CAF is dramatically inhibited after reduction with 2
      mercaptoethanol (2-ME), clearly demonstrating that CAF is sensitive to reduction
      with 2-ME and confirming a sulhydryl-dependent protein. The optimal activity of
      CAF is observed in the range of 35-45 degrees C and its half-life at 37 degrees C
      is about 105 h. Furthermore, the relative activity of CAF increases and gradually
      approaches a plateau level with the increase of Mg2+ concentration. Obviously,
      complement activation induced by CAF depends on adequate Mg2+ concentration,
      confirming that this dependence is characteristic of the alternative pathway.

PMID- 9586580
TI  - Determination of uric acid in scalp hair for non-invasive evaluation of uricemic
      controls in hyperuricemia.
AB  - The uric acid concentration in blood has been widely accepted as a diagnostic
      indicator of hyperuricemia and gout, and its assay method is well established. In
      the present study, we developed a simple and rapid method for the determination
      of uric acid in hair, which can be obtained non-invasively. The concentration
      (nmol/mg hair) of uric acid extracted from 10-20 mg hair with 0.1 M potassium
      hydroxide was determined by an enzymatic method using uricase. The concentration
      of uric acid (nmol/mg hair, mean+/-S.D.: 0.49+/-0.157, n=16) in hair from
      hyperuricemic patients was significantly higher than that (0.26+/-0.107, n=8) in
      healthy volunteers (p<0.01). The within-run and between-day precision (CVs) of
      the assay was 9.6-10.3% (n=10 each) and 11.6-16.3% (n=7 each), respectively. The
      concentration (nmol/mg hair, y) of uric acid in hair correlated well with that in
      serum (mg/l, x): y=0.09x-0.12 (r=0.75, Syx=0.122, n=23). Changes in the
      concentration of uric acid in the hair of antihyperuricemic drug-treated patient
      paralleled that in serum, suggesting that the concentration of uric acid in hair
      is a reliable indicator of the metabolic control in hyperuricemia.

PMID- 9586581
TI  - Release of nitric oxide from a spin trap, N-tert-butyl-alpha-phenylnitrone, under
      various oxidative conditions.
AB  - Nitric oxide (NO) generation from a spin trap, N-tert-butyl-alpha-phenylnitrone
      (PBN) under various oxidative conditions was examined. The absorbance of PBN at
      295 nm decreased with time of UV-irradiation, showing that PBN was decomposed by
      UV irradiation. The hydroxyl radical formed from a Fenton reagent also decomposed
      PBN, but there was little effect by a peroxyl radical and a superoxide. Nitrite,
      an oxidative product of NO, in PBN solution was determined using a NOx analyzer
      based on Griess reaction. UV-irradiation and the hydroxyl radical also formed
      nitrite. Direct detection of NO from the sample on reaction with hydroxyl radical
      was successful using a GC/MS/SIM on the UV-irradiated sample. NO generated in PBN
      solutions activated guanylate cyclase. From these results, PBN is viewed as a new
      kind of medicine which acts as an antioxidant and as an NO donor in vivo.

PMID- 9586582
TI  - Sexual difference of hepatic calcium-binding protein regucalcin mRNA expression
      in rats with different ages: effect of ovarian hormone.
AB  - The sexual difference of calcium-binding protein regucalcin mRNA expression in
      the liver of rats was investigated by Northern blot analysis. Liver regucalcin
      cDNA (0.9 kb of open reading frame) was used as a probe. The analysis of total
      RNAs extracted from various tissues of rats indicated that regucalcin mRNA was
      present primarily in the liver with a size of 1.8 kb. Hepatic regucalcin mRNA was
      expressed in male rats more than in females. This sexual difference was also seen
      in aged rats (50 weeks old), although the expression was decreased with
      increasing age. Ovariectomy did not cause a significant alteration in hepatic
      regucalcin mRNA levels. The subcutaneous administration of 17beta-estradiol (0.2
      mg/100 g body weight) in ovariectomized rats did not cause an appreciable
      increase in hepatic mRNA levels. The results demonstrate that regucalcin mRNA
      expression in rat liver is based on sex, and that this difference may not be
      related to estrogen.

PMID- 9586583
TI  - Competitive inhibition of delta8-tetrahydrocannabinol and its active metabolites
      for cannabinoid receptor binding.
AB  - In vitro binding characteristics of delta8-tetrahydrocannabinol (delta8-THC) and
      its metabolites, 11-hydroxy-delta8-THC (11-OH-delta8-THC) and 11-oxo-delta8-THC,
      as well as an inactive metabolite, delta8-THC-11-oic acid, as a cannabinoid
      receptor site from bovine cortex were examined using the specific agonist [3H]CP
      55940. 11-OH-delta8-THC and 11-oxo-delta8-THC strongly inhibited the specific
      binding of [3H]CP-55940. The Ki values of 11-OH-delta8-THC and 11-oxo-delta8-THC
      for the specific binding of [3H]CP-55940 were 52 and 143 nM, respectively,
      whereas that of delta8-THC-11-oic acid was 917 nM. Scatchard plot analyses
      indicated that 11-OH-delta8-THC and 11-oxo-delta8-THC caused a significant
      increase in the apparent KD value without changing the apparent Bmax. These
      results reveal that active metabolites of delta8-THC also competitively bind to
      the cannabinoid receptor as agonists.

PMID- 9586584
TI  - A novel anti-allergic drug, betotastine besilate, suppresses interleukin-5
      production by human peripheral blood mononuclear cells.
AB  - The effect of a novel anti-allergic drug, betotastine besilate (betotastine) on
      interleukin (IL)-5 production by human peripheral blood mononuclear cells (PBMC)
      was investigated. PBMC of Dermatophagoides farinae extract (Df)-sensitive donors
      produced IL-5 and showed a proliferative response upon stimulation with relevant
      antigen (10 microg/ml). Df-induced IL-5 production by PBMC was significantly
      inhibited by betotastine at 10 and 100 microM. Betotastine also suppressed
      proliferation of PBMC with less potency. The effect of betotastine on IL-5
      production was enhanced and significant even at 0.1 microM when the drug was
      added 120 min before antigen stimulation. Ketotifen and cetirizine also inhibited
      IL-5 production, but the effects of these drugs were significant only at 100
      microM. These findings indicate that the suppression of IL-5 production may be
      involved in the anti-allergic effect of betotastine.

PMID- 9586585
TI  - Effects of treatment with nimustine (ACNU), a bifunctional alkylating anticancer
      agent, on cultured resting L1210 cells.
AB  - Resting L1210 cells were treated with nimustine (ACNU), a bifunctional alkylating
      anticancer agent, for 2 h in a nutrient-depleted medium. The cells were then
      transferred to a fresh medium and incubated for a further 48 h. Functions of the
      cells thus prepared were examined in terms of the dye-exclusion of the membrane,
      2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] -2H
      tetrazolium hydroxide, inner salt, sodium salt (XTT)-reducing ability of the
      mitochondria, and heat generation due to vital metabolism as the measure of cell
      viability. The cells treated with ACNU were functioning normally in all the cell
      functions examined but were completely devoid of proliferating capacity. These
      results suggest the possibility that ACNU might impair the proliferative capacity
      of the resting cell population inside a solid tumor without causing such
      impairment to the cells of normal organs and tissues composed of intrinsically
      non-proliferative cells.

PMID- 9586586
TI  - Effects of codeine on the agitating force and gastrointestinal transit time in
      dogs, for use in drug absorption studies.
AB  - Drug absorption studies using dogs have been difficult because of different
      gastrointestinal(GI) conditions between dogs and humans, including dogs' shorter
      intestinal transit time and strong agitation force in the GI tract. We attempted
      to modify the agitation force and GI transit time in dogs using codeine. The
      agitation force was examined based on the in vitro/in vivo correlation for a CR
      tablet of acetaminophen showing agitation-dependent release. Codeine improved the
      GI condition better than atropine or loperamide, employed previously.

PMID- 9586587
TI  - Participation of P450-dependent oxidation of isoniazid in isonicotinic acid
      formation in rat liver.
AB  - By determining the formation amount of isonicotinic acid (INA) from isonicotinic
      acid hydrazide (isoniazid:INH) in isolated rat hepatocytes, we were able to
      identify the involvement of the oxidative cleavage of the acid hydrazide. INA
      formation from INH increased significantly using the isolated hepatocytes
      prepared from rats pretreated with phenobarbital (PB), 3-methylcholanthrene
      (3MC), dexamethazone (DEX) and rifampicin (RIF), respectively, in comparison to
      the control group. On the other hand, a remarkable decrease in INA formation from
      INH was observed by the addition of such P450 inhibitor as metyrapone or
      cimetidine as well as an amidase inhibitor bis(p-nitrophenyl)phosphate (BNPP) to
      the isolated hepatocytes prepared from PB-pretreated rats. By further experiments
      using rat hepatic microsomes, the oxidative pathway of INA formation in INH
      metabolism was determined to be P450-dependent, since NADPH and oxygen were both
      essential for the oxidative pathway of INH to INA and the amount of INA formation
      was also significantly increased by P450 inducers. Regarding acetylisoniazid
      (AcINH) and isonicotinic acid amide (INAA), however, INA formation by P450 was
      little observed in the microsomal experiments.

PMID- 9586588
TI  - Long-term administration of "sho-saiko-to" increases cytochrome P-450 mRNA level
      in mouse liver.
AB  - Simplified differential display of mRNA was applied to isolate and identify genes
      transcriptionally regulated in mouse liver by sho-saiko-to administration. A cDNA
      fragment up-regulated by sho-saiko-to was isolated and characterized. cDNA
      sequencing and subsequent database analysis revealed that the fragment showed
      significant sequence similarity with mouse testosterone 16-alpha-hydroxylase
      (cytochrome P-450[16alpha]) cDNA. The increased level of mRNA expression of
      cytochrome P-450(16alpha) in association with sho-saiko-to administration
      suggests the molecular mechanism of the chemopreventive effect of sho-saiko-to.
      This result indicates the usefulness of the mRNA differential display technique
      to investigate the molecular mechanism of Kampo medicine.

PMID- 9586589
TI  - Current trends in management of men with lower urinary tract symptoms and benign
      prostatic hyperplasia.
AB  - Management of lower urinary tract symptoms (LUTS) and benign prostatic
      hyperplasia (BPH) has been central to urology for decades. The urologic community
      has increasingly come to realize that many men with LUTS do not have prostate
      enlargement and do not need their prostates debulked surgically. Of all the
      factors that have emerged to alter the trends associated with management of LUTS
      and BPH, none has had more impact than the advent of medical therapy. The
      selective, long-acting, alpha1-blocking agents terazosin, doxazosin, and
      tamsulosin have become most popular because of their specificity in the urinary
      tract, reduced side effects, and simplicity of dosage. In addition, finasteride,
      a 5-alpha-reductase inhibitor, was found to be effective in men with prostates of
      > or = 40 g. Furthermore, the larger the prostate at baseline, the greater the
      efficacy of finasteride on symptom relief and flow rate improvement. In addition
      to medical therapy, an array of device therapies has emerged in the management of
      LUTS and BPH. Laser prostatectomy is the oldest of the device therapies and
      includes transurethral vaporization of the prostate (VLAP), transurethral
      evaporation of the prostate (TUEP), and transurethral interstitial laser
      prostatectomy (TILP). Studies report beneficial outcomes approaching those
      achieved with transurethral resection of the prostate (TURP) with less morbidity
      and a shorter hospital stay. Common diseases contribute the most to national
      healthcare expenditures. The management of LUTS and BPH are such disorders and
      result in the expenditure of vast healthcare resources worldwide. The surgical
      strategies have an established record of outcomes documenting their potential for
      symptom relief and the avoidance of future complications. Medical and device
      therapies, although currently promising and attractive, therefore must prove
      comparable durability.

PMID- 9586590
TI  - Natural history and epidemiology of benign prostatic hyperplasia: relationship
      among urologic measures.
AB  - Numerically weak correlations can stem from research studies for numerous
      reasons, some of which have little to do with lack of true physiologic
      relationships. Previous investigators have reported relatively weak correlations
      among urologic measures, mostly based on patients referred to urologic clinics.
      Such samples of patients may be prone to self-selection or referral bias. Men
      seeking medical care for urinary symptoms are more likely to have more severe
      symptoms, low urinary flow rates, and prostatic enlargement, and hence clinic
      based samples may reflect a narrow spectrum in urologic measures, resulting in
      attenuated correlation coefficients. Measurement error in the technique or
      equipment, lack of specificity, and within-patient variability can also attenuate
      correlations. Thus, the characteristics of the sample upon which correlations are
      calculated must be considered in the interpretation of the magnitude of
      relationships among measurements. Possibly due to the broader spectrum, community
      based studies have recently found modest but somewhat stronger relationships
      among urologic measures than previously documented. Such correlations are
      comparable to those found in other disease areas. In addition, such studies have
      documented that symptoms, urinary flow rate, and prostatic enlargement are
      predictive of long-term complications, such as acute urinary retention, with
      predictive relationships comparable to those found in other disease areas. Thus,
      the relationships among and predictive ability of urologic measures may be
      stronger than currently appreciated.

PMID- 9586591
TI  - Comprehensive patient evaluation for benign prostatic hyperplasia.
AB  - It is time to consider new approaches to benign prostatic hyperplasia (BPH).
      Previously, obstruction, prostatism, and hyperplasia of the prostate were
      considered to be almost synonymous. Today, there is increasing awareness that
      some men have hyperplasia, some have symptoms, and others obstruction. Currently,
      BPH is discussed in terms of benign prostatic enlargement (BPE), bladder outlet
      obstruction (BOO), and lower urinary tract symptoms (LUTS). Symptom
      questionnaires, uroflowmetry, prostate volume determination, residual urine
      volume determination, and pressure-flow studies continue to be the instruments
      used for assessing BPH patients. Prostate enlargement, prostatic muscle tone, and
      bladder function all impact voiding function. A large part of BPH symptomatology
      may be explained by bladder dysfunction, which tends to be discounted in
      discussions about BPH. In the future, bladder dysfunction must receive more
      attention, and better measures should be developed to quantify it. Postvoid
      residual urine is a sign of abnormal bladder function rather than the result of
      BOO. However, variability limits the predictive value of residual urine volume.
      Uroflowmetry is also criticized for excessive variability, which is increased
      among men with LUTS secondary to BPH. Approximately 70% of men with uroflow < 15
      mL/sec are obstructed, which means that at least 10 million men in the United
      States have BOO. Therefore, alleviation of obstruction would be a daunting and
      overwhelming task. It is still widely believed that prostatism is due to an
      enlarged prostate and can be cured by reducing the size of the prostate. Prostate
      volume can be used to select treatment, but it is not reasonable to decide
      whether to treat a patient with LUTS on the basis of prostate size. One of the
      problems with symptom-based treatment is that LUTS is not gender specific.
      Questions about LUTS in patients with BPH may elicit very inconsistent responses,
      and numeric improvement in symptom score is not proportional to how bothered the
      patient is. Bother, not symptom score or objective measures such as postvoid
      residual urine and uroflowmetry, is what drives the decision-making process in
      BPH management. The most recent international guidelines for BPH treatment
      emphasize that the degree to which the patient is bothered is more important than
      symptom score. More than a third of all elderly men (and women) have moderate or
      severe LUTS, and not all of them should receive treatment. In the future,
      measuring bother due to LUTS and impact on the patients' quality of life with the
      BPH impact should be imperative and central to treatment decisions.

PMID- 9586592
TI  - Accurate determination of prostate size via digital rectal examination and
      transrectal ultrasound.
AB  - Previously, prostate size did not play a significant role in the choice of
      treatment for benign prostatic hyperplasia (BPH). It has been postulated that
      prostate size does not correlate with symptom severity, flow rate, or the
      presence or absence of obstruction. However, in a published study of community
      dwelling men, the odds of having moderate to severe symptoms were five times
      higher for men with enlarged prostates than for those with normal prostates.
      Response to certain types of BPH therapy, especially finasteride, depends on
      actual prostate volume. Therefore, it is important to have a simple way to
      accurately determine if a patient's prostate is enlarged. In an analysis of four
      studies, there was a distinct underestimation of prostate size by digital rectal
      examination (DRE) when compared with transrectal ultrasound (TRUS) measurement.
      The underestimation of prostate volume increased with increasing TRUS volume,
      particularly if the volume was greater than 30 mL. The average underestimation
      was between 9% and 12% for prostate volumes 30 to 39 mL and between 17% and 27%
      for prostate volumes 40 to 49 mL. Because of these results, a prospective study
      is currently in progress to develop models or visual aids to assist physicians in
      more accurately predicting a threshold prostate volume via DRE.

PMID- 9586593
TI  - Recent developments in the surgical management of benign prostatic hyperplasia.
AB  - A new era in the surgical management of benign prostatic hyperplasia (BPH) has
      emerged in the past decade. A variety of less invasive treatment modalities have
      been introduced and well-established surgical treatments are being reassessed.
      Although progress has been made in the management of BPH, the substantial
      economic burden to the healthcare system caused by BPH emphasizes the importance
      of cost-effective treatment. Open prostatectomy is the most efficient BPH
      treatment for relieving symptoms and improving uroflow, but it is also the most
      invasive and morbid. Transurethral resection of the prostate (TURP) is still the
      "gold standard" for treatment of BPH, but open prostatectomy has been reported to
      have a lower perioperative mortality than TURP, and low retreatment rates reduce
      the long-term cost. The morbidity associated with TURP, such as impotence or
      urinary incontinence, has been reduced in recent years while new features, such
      as performing TURP under local anesthesia and bipolar electrosurgical techniques,
      have been introduced. Transurethral electrovaporization of the prostate (TVP) is
      a recent modification of TURP that has rapidly gained popularity. TVP greatly
      reduces TURP syndrome, provides good hemostasis, and may reduce catheterization
      and hospitalization times. Transurethral incision of the prostate (TUIP) is
      another safe and inexpensive procedure that is well-documented and comparable to
      TURP in long-term efficacy. TUIP is an underused procedure with which the newer,
      less invasive treatments should be compared. Whereas the well-established
      surgical treatments primarily relieve obstruction by tissue ablation, some of the
      newer treatment modalities may ameliorate lower urinary tract symptoms (LUTS)
      with minimal urodynamic change. In some of the newer nonresection treatments, no
      major significant postoperative reduction in prostate volume can be demonstrated.
      Laser treatments are based on a broad variety of techniques, generators, and
      fibers, of which most have initially demonstrated promising results. Well-known
      techniques include visually laser-assisted prostatectomy (VLAP) and interstitial
      laser coagulation (ILC). The laser techniques are generally not as effective as
      TURP, but are safe under local anesthesia on an outpatient basis with low
      complication rates. Transurethral microwave thermotherapy of the prostate (TUMT)
      and radiofrequency transurethral needle ablation (TUNA) are minimally invasive,
      safe new therapies. There is some evidence that the procedures create long-term,
      alpha-adrenoceptor-like blockade. Complications, except for transient
      catheterization in up to 40% of patients, may be practically nonexistent. The
      cost is difficult to estimate and the long-term outcome is still to be assessed.
      If the newer, less invasive treatment modalities provide stable long-term results
      and competitive costs, they will be tempting alternatives to prostate resections
      and may also challenge medical therapy.

PMID- 9586594
TI  - Minimally invasive alternative therapeutic options for lower urinary tract
      symptoms.
AB  - Many minimally invasive techniques designed to alleviate lower urinary tract
      symptoms have been evaluated, each of which offers a glimpse of the next
      generation of treatment. These minimally invasive techniques improve upon
      transurethral resection of the prostate (TURP) by reducing the risk of
      postoperative complications. However, none have been compared with TURP in large
      scale controlled trials, and therefore will not be able to replace TURP until
      their long-term durability is known.

PMID- 9586595
TI  - Overview of alpha-blocker therapy for benign prostatic hyperplasia.
AB  - Management of benign prostatic hyperplasia (BPH) is rapidly changing. Established
      surgical procedures are being replaced by minimally invasive modalities such as
      electrovaporization and transurethral needle ablation. Improved understanding of
      pathophysiology and developments in molecular biology has provided drugs for
      alleviating the symptoms of prostatic enlargement. Currently, medical therapy is
      the first-line treatment modality in the management of BPH. There are two types
      of medical treatment available: alpha-adrenoceptor-blockers and 5-alpha-reductase
      inhibitors. Alpha-blockers relieve the dynamic component of obstruction whereas 5
      alpha-reductase inhibitors relieve the mechanical component of obstruction. At
      present, alpha-blockers are used most frequently. However, they do have
      significant cardiovascular side effects. More uroselective alpha-blockers have
      recently become available and may reduce the risk of cardiovascular side effects.
      This review summarizes relevant literature on the use of alpha-blockers in the
      treatment of BPH.

PMID- 9586596
TI  - Meta-analysis of randomized clinical trials of finasteride.
AB  - A meta-analysis was recently published based on six randomized clinical trials of
      at least one year duration involving finasteride 5 mg and placebo in the
      treatment of men with clinical benign prostatic hyperplasia (BPH). In a pooled
      analysis, mean improvement in symptoms and urinary flow rate with finasteride
      were found to increase with increasing prostate size. This article reviews the
      previous publication of this meta-analysis, which indicated prostate volume is a
      key predictor of outcomes with finasteride treatment and suggested that
      finasteride is most effective in men with large prostates.

PMID- 9586597
TI  - Long-term implications of medical therapy on benign prostatic hyperplasia end
      points.
AB  - There is a progression over time of relevant measurable benign prostatic
      hyperplasia (BPH) end points including symptoms, flow rates, prostate size,
      complications such as acute urinary retention (AUR), and surgical rates. Only two
      classes of medical therapy, the alpha-blockers and a 5-alpha-reductase inhibitor,
      have shown unequivocal and consistent efficacy over placebo in 1-year studies.
      Both of these classes of medications have demonstrated relative long-term safety.
      Finasteride has been shown in three large, 2-year, randomized, controlled studies
      to be superior to placebo, and both finasteride and the alpha-blockers have
      demonstrated long-term efficacy and safety in open-label studies. The efficacy of
      finasteride is significantly enhanced when it is used in patients with large
      prostates. Long-term finasteride therapy also results in a significant reduction
      in the incidence of AUR and the need for surgery. Long-term medical therapy for
      BPH is effective and safe. Data are now available that allow clinicians to
      analyze the long-term risks and benefits of the various medical options and
      subsequently rationalize long-term therapy for individual patients.

PMID- 9586598
TI  - Biologic variability of prostate-specific antigen and its usefulness as a marker
      for prostate cancer: effects of finasteride. Finasteride PSA Study Group.
AB  - OBJECTIVES: The effects of finasteride on prostate-specific antigen (PSA)
      variability and usefulness in prostate cancer detection were examined. METHODS:
      Percent change and crossover of PSA levels between the low (1.0 to 3.9 ng/mL) and
      high (4.0 to 10.0 ng/mL) ranges were evaluated in 72 men with benign prostatic
      hyperplasia (BPH) and 77 men with both BPH and prostate cancer (PCa) treated with
      finasteride or placebo for 6 months. Patients with PCa were studied as a model
      for evaluating the effects on PSA levels in patients with BPH and latent PCa. As
      recommended on the product label, PSA levels for finasteride-treated patients
      were doubled for interpretation. RESULTS: In patients with BPH, most placebo- and
      finasteride-treated patients with low PSA levels at baseline had subsequent PSA
      levels below 4.0 ng/mL throughout the study. Among patients with high baseline
      PSA levels, only 1 of 17 finasteride-treated patients, compared with 8 of 13
      placebo-treated patients, crossed into the low range. In the BPH/PCa study, most
      placebo-treated patients maintained PSA levels in the same range (15 of 19 less
      than 4.0 ng/mL; 14 of 16 greater than 4.0 ng/mL). Almost one third of finasteride
      treated patients with low PSA levels at baseline crossed into the high range (8
      of 22), whereas most patients with high PSA levels at baseline were not masked
      with treatment, with PSA levels remaining high (12 of 15). CONCLUSIONS: PSA
      levels cross between the low and high PSA ranges in both finasteride- and placebo
      treated patients with BPH and those with both BPH and PCa. Doubling the PSA
      levels in finasteride-treated patients allows appropriate interpretation of PSA
      values and does not mask the detection of PCa.

PMID- 9586599
TI  - Army and Air Force leadership in the Prostate Cancer Prevention Trial.
AB  - Prostate cancer is now the most common solid tumor in men in the United States.
      Although the current public health approach to this disease is early diagnosis
      and treatment, investigations are also focusing on the possibility of disease
      prevention. The Prostate Cancer Prevention Trial, begun in 1993, has completed
      recruitment of 18,000 men who will be randomized to receive either finasteride or
      placebo to determine if finasteride can prevent the development of this disease.
      Both Army and Air Force institutions are participating in this trial, with four
      Department of Defense institutions contributing over 10% of the patients
      randomized. The results of this study may have a major impact on active duty
      personnel for whom prevention of prostate cancer may become possible.

PMID- 9586600
TI  - Accuracy of biopsy Gleason scores from a large uropathology laboratory: use of a
      diagnostic protocol to minimize observer variability.
AB  - OBJECTIVES: To examine the correlation of biopsy Gleason scores with radical
      prostatectomy specimens from a laboratory that uses protocols designed to
      minimize observer variability. This protocol mandates consensus case review of
      all nonbenign cases. METHODS: Between August 24, 1993 and June 26, 1997, 106
      patients who underwent radical prostatectomy at Johns Hopkins Hospital,
      Baltimore, Maryland had their prostate cancer diagnosed and graded at one
      laboratory (DIANON Systems). We analyzed the Gleason scores from the biopsy and
      radical prostatectomy specimens. RESULTS: Exact correlation existed between
      biopsy and radical prostatectomy Gleason scores for 72 (68%) cases; 103 (97%)
      correlated within 1 grade, all cases correlated within 2 grades; 26 (25%)
      biopsies were undergraded and 8 (8%) were overgraded. Positive predictive values
      for biopsy Gleason scores 5, 6, and 7 were 66%, 67%, and 71%, respectively.
      Grouped Gleason scores (well differentiated [2 to 4], moderately differentiated
      [5, 6], moderately to poorly differentiated [7], and poorly differentiated [8 to
      10]) correlated exactly for 74 (70%) cases and within 1 group for all cases.
      Patient age, digital rectal examination results, total number of positive cores,
      and maximum percentage of tumor on biopsy did not affect correlation, but
      prostate-specific antigen (PSA) levels did affect correlation (exact correlation
      96% when the PSA level was less than 5 ng/mL; 50% when the PSA level was 11 ng/mL
      or greater, P <0.01). CONCLUSIONS: The combination of experience and the protocol
      described minimizes intra- and interobserver variability, thereby improving the
      predictive value of biopsy Gleason grading. Biopsy and radical prostatectomy
      Gleason scores correlate more poorly when the PSA level is high (11 ng/mL or
      greater) than when the PSA level is low (less than 5 ng/mL).

PMID- 9586601
TI  - Positive prostate biopsy rate consistently increases with age at the same
      prostate-specific antigen level in patients with normal digital rectal
      examination.
AB  - OBJECTIVES: To examine the relationship between positive prostate biopsy rates
      and age over the range of serum prostate-specific antigen (PSA) concentrations of
      4 to 10 ng/mL. METHODS: The rates for adenocarcinoma were calculated for prostate
      biopsy specimens received at UroCor Inc., Oklahoma City, Oklahoma between April
      1995 and June 1997. The selection criteria were as follows: men between 50 and 79
      years of age, normal digital rectal examination (DRE), prebiopsy PSA level
      between 4.01 and 10.0 ng/mL obtained within a 4-month period prior to receipt of
      biopsy, and no previous prostate biopsy. Five thousand six cases were selected
      out of 81,545 prostate biopsy specimens submitted by office-based urologists. The
      rates of positive prostate biopsies were stratified by age in decade increments
      and by PSA in increments of 1 ng/mL. The P values were calculated by the chi
      square test. RESULTS: The patient mean age was 65.8 years. An overall increase in
      the positive prostate biopsy rate for men between 50 and 79 years of age as serum
      PSA increases from 4.01 to 10.0 ng/mL (P = 0.047) was found; however, this
      increase was less significant than the increase found in positive biopsy rates
      caused by age alone (P <0.0001). CONCLUSIONS: Undetected prostate cancer appears
      to be a major cause of the increasing serum PSA seen with advancing age.

PMID- 9586602
TI  - Role of magnetic resonance imaging in renal transplant recipients with acquired
      cystic kidney disease.
AB  - OBJECTIVES: To evaluate the impact of magnetic resonance imaging (MRI) in renal
      transplant recipients whose ultrasound (US) examinations of the native kidneys
      have met the criteria of acquired cystic kidney disease (ACKD). METHODS: The US
      scans of 840 renal allograft recipients were prospectively studied. In addition,
      46 of 169 patients diagnosed with ACKD by US scans underwent MR examination. MRI
      protocols included (a) T1 and T2-weighted fast spin echo imaging, (b) T2-weighted
      gradient echo imaging, and (c) gadolinium-enhanced T1-weighted imaging in 7
      patients with evidence of complex cysts. In the case of complex lesions, both US
      and MRI follow-up examinations were performed between 6 and 12 months after the
      prior examination. RESULTS: US examination showed ACKD in 169 of 840 patients. In
      addition, US revealed 8 patients with renal cell carcinomas (RCC). Of these 8
      patients, 7 had evidence of ACKD. The median number of cysts depicted on US
      examination in native kidneys of renal transplant recipients was 3 (range 0 to
      10) on both sides. MRI revealed significantly more and smaller cysts compared to
      US. The median number of cysts was seven on the left and nine on the right native
      kidneys, respectively. MRI revealed 18 complex lesions in 7 patients. Thirteen of
      18 complex lesions were undetected by US. CONCLUSIONS: MRI is superior to US in
      depiction of simple and complex lesions of native kidneys in renal allograft
      recipients. MRI exhibits no overestimation of the prevalence of ACKD on the basis
      of the US criteria already mentioned. Advantages of MRI do not justify routine
      screening tests by this imaging modality. However, MRI should be used for further
      evaluation of complex lesions detected by US.

PMID- 9586603
TI  - Metachronous renal cell carcinoma metastasis to the contralateral adrenal gland.
AB  - OBJECTIVES: Metachronous metastasis of renal cell carcinoma to the contralateral
      adrenal gland is very rare. We review our experience with 5 such patients and
      compare it with reports in the literature. METHODS: The records of all 350
      patients who underwent nephrectomy for renal cell carcinoma in our center between
      1975 and 1992 were reviewed. Five patients were found to have had solitary
      metachronous metastases to the contralateral adrenal gland on follow-up. RESULTS:
      The adrenal metastasis was discovered 18 to 210 months (mean 66.8) after
      nephrectomy. In 2 patients the lesion was found incidentally on routine computed
      tomography scan; in the other 3 patients, diagnosis was by ultrasonography,
      performed because of flank pain and weight loss or routine follow-up. All
      patients underwent adrenalectomy. Survival ranged from 8 to 64 months (mean
      36.4); 3 patients had no evidence of disease at 42, 44, and 64 months
      postoperatively, and 2 patients died of pulmonary metastasis at 8 and 24 months.
      Analysis of the clinical data of our 5 patients together with the 9 we found in
      the published reports revealed that the mean interval between nephrectomy and the
      appearance of adrenal metastasis was shorter in the patients who died.
      CONCLUSIONS: The results of adrenalectomy for metachronous metastasis of renal
      cell carcinoma to the contralateral adrenal gland are unpredictable. The
      prognosis is somewhat better when the mean interval between the nephrectomy and
      the appearance of the adrenal metastasis is longer than 18 months. We recommend
      adrenalectomy because long-term survival is expected in some of these patients.

PMID- 9586604
TI  - Extracorporeal shock wave lithotripsy for lower pole nephrolithiasis: efficacy
      and variables that influence treatment outcome.
AB  - OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) for the treatment of
      lower caliceal stones (LCS) tends to have a poor success rate, prompting many
      urologists to advocate alternative treatment modalities. This study attempts to
      identify variables that may influence the outcome of ESWL treatment for LCS to
      help in selecting patients that are likely to benefit from the treatment.
      METHODS: One hundred forty-two patients with isolated LCS treated with the
      Dornier HM3 lithotriptor were reviewed. The study data include characteristics of
      patients, stones, urinary tract treated, previous treatment of stones in the same
      kidney, and details of the ESWL treatment. RESULTS: Eighty patients (56%) were
      stone free 3 months after ESWL. Multivariate analysis with logistic regression
      identified six independent and significant variables that influenced treatment
      outcome: these included number of stones (P = 0.001), previous percutaneous
      nephrostolithotomy (PNL) treatment (P = 0.001), side of the stone (P = 0.002),
      presenting stone type (P = 0.004), number of ESWL sessions (P = 0.01), and
      maximum kilovoltage setting of ESWL at treatment (P = 0.02). Stone size did not
      influence the treatment outcome in this study. CONCLUSIONS: ESWL provides an
      acceptable first line treatment for patients with LCS. Patients who fail ESWL and
      have poor prognostic features (ie, multiple LCS, hard stones requiring high
      voltage and multiple ESWL sessions, lower caliceal stone formation secondary to
      ESWL treatment of stones in other locations of the renal unit, or previous
      treatment with PNL) should be counseled for alternative treatment modalities.

PMID- 9586605
TI  - Cardiac arrhythmias with external fixed-rate signal generators in shock wave
      lithotripsy with the Medstone lithotripter.
AB  - OBJECTIVES: To evaluate the incidence and outcome of cardiac arrhythmias
      associated with an external fixed-rate generator and the Medstone lithotripter
      with regard to stone location, anesthesia type, patient age, and gender. METHODS:
      Data were obtained on 933 patients who underwent shock wave lithotripsy (SWL)
      with the Medstone lithotripter. Patients were randomly divided into two study
      groups, including those with pre-existing cardiac disease, hypertension, and
      cardiac medications. Group 1 (576 patients) were treated with the external fixed
      rate signal generator (cardiac simulator). Group 2 (357 patients) underwent
      electrocardiogram-gated SWL (no simulator). All patients were monitored for
      arrhythmias during SWL. Patients who developed arrhythmias on the simulator were
      converted to gated SWL. RESULTS: In group 1, 463 patients (80%) had no
      arrhythmias during treatment, whereas 113 patients (20%) developed cardiac
      arrhythmias (primarily premature ventricular contractions [PVCs]) and were
      successfully converted to gated SWL. Only 1 patient in group 2 (0.3%) had a
      documented arrhythmia (PVC). Group 1 patients who developed arrhythmias with a
      cardiac simulator were more likely to have renal rather than ureteral stones. Chi
      square analysis showed a significant correlation between patients with and
      without arrhythmias in group 1 with regard to stone location (P <0.0001). In
      group 1, regional anesthesia, intravenous anesthesia, and general anesthesia had
      an arrhythmia rate of 14%, 27%, and 38%, respectively. The only patient in group
      2 who developed arrhythmias was under general anesthesia. The differences between
      groups 1 and 2, with regard to anesthesia type and arrhythmia, were statistically
      significant (P <0.001). No patients required additional medical therapy or
      hospitalization for cardiac events, and all patients safely completed the SWL
      treatment. CONCLUSIONS: With careful monitoring and adequate precautions,
      external fixed-rate signal generators are safe, effective methods for pacing the
      Medstone shock wave lithotripter and probably other extracorporeal shock wave
      lithotripters.

PMID- 9586606
TI  - Ureteral repair with titanium staples: comparison with suture closure.
AB  - OBJECTIVES: Vascular closure staple (VCS) clips made of titanium were initially
      developed for microvascular anastomoses with little knowledge of their
      effectiveness in larger tubular tissue structures. This study compares VCS clips
      and sutures in the closure of longitudinal ureterotomy incisions. METHODS: In 9
      pigs, 1-cm-long anterior, longitudinal ureterotomy incisions were randomly
      assigned to closure with either 4-0 interrupted polyglactin sutures or VCS clips.
      RESULTS: Clip closure was significantly faster (74+/-28 versus 534+/-182
      seconds). All 18 ureters were patent and without signs of leakage, calculus
      formation, or stenoses after 3 months. Clip closure resulted in slightly but not
      statistically significantly less narrowing of the duct lumen, but there was no
      difference in wall thickness at the repair site. At histologic examination, all
      18 incisions healed without signs of acute inflammation or marked fibrosis.
      CONCLUSIONS: Ureterotomy closure with VCS clips results in wound healing that is
      as effective as suture closure, with a comparable degree of narrowing. The time
      required for clip closure is only about 1/7 that required for suture closure.

PMID- 9586607
TI  - Percentage of free serum prostate-specific antigen as a predictor of pathologic
      features of prostate cancer in a screening population.
AB  - OBJECTIVES: Measurement of the percentage of free prostate-specific antigen
      (%FPSA) in serum can improve the specificity of prostate cancer screening. We
      evaluated the ability of %FPSA to predict pathologic features of screen-detected
      clinically localized prostate cancer. METHODS: We evaluated the correlation
      between %FPSA in serum before cancer diagnosis and the pathologic features of the
      cancers detected in 108 men with clinically localized prostate cancer who were
      treated with radical prostatectomy and for whom complete embedding of the radical
      prostatectomy specimen was performed. Ninety-seven men (90%) had a previous
      negative screening evaluation before prostate cancer was detected. RESULTS: There
      was a negative correlation of %FPSA with penetration of cancer through the
      prostatic capsule, cancerous surgical margins, Gleason score, percentage of
      cancer in the gland, and tumor volume (r = -0.2 to -0.4). After controlling for
      other preoperative predictors, %FPSA predicted capsular penetration (adjusted
      odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1 to 2.4, for each 5%
      decrease in %FPSA) and cancer volume 0.5 cc or greater (adjusted OR 1.6, 95% CI
      1.1 to 2.3). Preoperative %FPSA also predicted possibly harmless cancer (OR 1.5,
      95% CI 1.1 to 2.2, for each 5% increase in %FPSA). CONCLUSIONS: In a select group
      of men for whom cancer was detected early via screening, a lower %FPSA in serum
      suggests a potentially more threatening cancer. This information may aid patients
      and clinicians in making more informed decisions about the management of prostate
      cancer, such as selecting patients for watchful waiting. However, more research
      is needed to determine the performance characteristics of %FPSA in clinical
      practice.

PMID- 9586608
TI  - Serum prostate-specific antigen profile following radiotherapy for prostate
      cancer: implications for patterns of failure and definition of cure.
AB  - OBJECTIVES: A reference range of prostate-specific antigen (PSA) values
      compatible with cure following radiotherapy (RT) for prostate cancer (PCa) has
      yet to be established. Various thresholds, as low as 0.5 ng/mL, have been used to
      define biochemical disease-free status. We report PSA profiles in 118 patients
      who were systematically biopsied following standard RT, with a minimum 4-year
      follow-up. METHODS: One hundred eighteen patients were treated with standard
      external beam RT from May 1987 to October 1991, and were followed prospectively
      with transrectal ultrasound (TRUS)-guided biopsies and measurement of serum PSA
      levels. Stage distribution was as follows: T1b: 25 patients, T2a: 27 patients,
      T2b/c: 42 patients, T3: 23 patients, T4: 1 patient. Median follow-up for patients
      without clinical failure is 68 months (range 48 to 108). Treatment failures were
      categorized as biochemical (biochemical failure [chemF]: PSA level of 2.0 ng/mL
      or more and greater than 1 ng/mL over nadir), local (local failure [LF]: positive
      biopsy and PSA level greater than 2.0), and distant failure (DF). RESULTS: PCa
      recurred in 55% of patients: 38% LF (n = 45; 30 isolated and 15 with DF), 25% DF
      (n = 30; 15 isolated and 15 with LF), and 4% chemF (n = 5). Mean PSA nadir was
      0.4 for patients with no evidence of disease (NED) and occurred at 33 months, 3.2
      for LF at 17 months, 7.7 for DF at 12 months, and 1.4 for chemF at 24 months.
      After reaching the nadir, PSA in patients with recurrence followed first-order
      kinetics, rising exponentially over time. The mean PSA doubling time was 12.6
      months for LF, 5.2 months for DF, and 21.8 months for chemF (P = 0.004). At last
      follow-up, the median PSA for patients without evidence of disease is 0.5 ng/mL.
      Four such patients had PSA values that rose to between 1 and 2 ng/mL for 5 to 38
      months, but these eventually fell again to less than 1 ng/mL. Three patients had
      PSA values between 2 and 3 ng/mL, but 2 now have decreasing levels and the third
      has a rising level. All patients whose PSA levels rose to greater than 3 ng/mL
      exhibited a persistently rising pattern and ultimate tumor recurrence.
      CONCLUSIONS: There is a range of PSA values following RT for PCa that is
      compatible with cure. A definition of biochemical disease-free status at any
      absolute threshold of PSA level less than 3 ng/mL will overdiagnose failure in a
      significant proportion of patients. Patients with a PSA level between 1.5 and 3
      ng/mL should be observed until there is unequivocal evidence of disease
      recurrence. In the absence of known biopsy status, PSA doubling time can be a
      useful indicator of whether failure is local or distant.

PMID- 9586609
TI  - Holmium laser resection of the prostate versus neodymium:yttrium-aluminum-garnet
      visual laser ablation of the prostate: a randomized prospective comparison of two
      techniques for laser prostatectomy.
AB  - OBJECTIVES: To directly compare holmium laser resection of the prostate (HoLRP)
      with neodymium:yttrium-aluminum-garnet visual laser ablation of the prostate
      (VLAP), which represent two fundamentally different methods of laser
      prostatectomy. METHODS: In a randomized, prospective comparison, a total of 44
      men with symptomatic benign prostatic hyperplasia (BPH) were treated with either
      HoLRP or VLAP. Standard preoperative assessment included American Urological
      Association (AUA) symptom score, peak urinary flow rates (Qmax), ultrasound
      prostate volume, and residual urine measurements. Pressure-flow urodynamics were
      performed preoperatively and at 3 months postoperatively. Intraoperative and
      perioperative factors were assessed. The patients were followed at 1, 3, 6, and
      12 months following the procedure. RESULTS: There were no significant differences
      between the patient groups for any preoperative parameter. The mean total
      operating time was longer in the HoLRP group (52 minutes) compared with the VLAP
      group (41 minutes) (P <0.01). The mean catheter times were 1.4 days (HoLRP) and
      11.6 days (VLAP) (P <0.001). These times included the 9% of patients undergoing
      HoLRP and 36% of patients undergoing VLAP who required recatheterization.
      Immediate postoperative dysuria scores were higher in the VLAP group compared
      with the HoLRP group. There were no significant differences in AUA scores between
      the two treatment groups at any postoperative interval. The Qmax values were
      greater at follow-up in the HoLRP group, but statistical significance was not
      achieved at 12 months. However, both PdetQmax and Schafer grade measurements
      taken at 3 months postoperatively were significantly lower in the patients
      undergoing HoLRP. Three patients (14%) required reoperation in the VLAP treatment
      arm but no patient who underwent HoLRP has required reoperation to date.
      CONCLUSIONS: HoLRP results in significantly improved patient outcomes compared to
      VLAP.

PMID- 9586610
TI  - Prevalence of a physician-assigned diagnosis of prostatitis: the Olmsted County
      Study of Urinary Symptoms and Health Status Among Men.
AB  - OBJECTIVES: To describe the occurrence of a physician-assigned diagnosis of
      prostatitis in a community-based cohort. METHODS: A sampling frame of all Olmsted
      County, Minnesota, male residents was used to randomly select a cohort of men
      between 40 and 79 years old by January 1, 1990, to participate in a longitudinal
      study of lower urinary tract symptoms. The 2115 participants (response rate 55%)
      completed a previously validated self-administered questionnaire that assessed
      the prevalence of lower urinary tract symptoms, including a history of
      prostatitis. Subsequently, all inpatient and outpatient community medical records
      of participants were reviewed retrospectively for a physician-assigned diagnosis
      of prostatitis from the date of initiation of the medical record through the date
      of the last follow-up. RESULTS: The overall prevalence rate of a physician
      assigned diagnosis of prostatitis was 9%. Men identified with the diagnosis of
      "prostatitis" had symptoms of dysuria and frequency and rectal, perineal,
      suprapubic, and lower back pain. Among men with a previous diagnosis of
      prostatitis, the cumulative probability of subsequent episodes of prostatitis was
      much higher (20%, 38%, and 50% among men 40, 60, and 80 years old, respectively).
      CONCLUSIONS: These findings indicate that the community-based prevalence of a
      physician-assigned diagnosis of prostatitis is high, of similar magnitude to that
      of ischemic heart disease and diabetes. Furthermore, once a man has an initial
      episode of prostatitis, he is more likely to suffer chronic episodes than men
      without a diagnosis. Although the pathologic mechanisms underlying these
      diagnoses are not certain, these data provide a first step toward understanding
      how frequently the diagnosis occurs in the community.

PMID- 9586611
TI  - Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment.
AB  - OBJECTIVES: Neuroendocrine differentiation (NED) is a common feature in
      adenocarcinoma of the prostate. Several studies suggest that NED may have a major
      impact on cancer progression as neuroendocrine (NE) secretory products have been
      shown to possess growth stimulatory effects. NED has also been proposed to
      constitute part of the mechanism by which a prostate cancer cell progresses
      toward androgen independence as NE tumor cells have been demonstrated to be
      devoid of androgen receptor immunoreactivity. In this retrospective study, we
      evaluated NED status in prostate cancer specimens from patients undergoing
      androgen ablation therapy. METHODS: The degree of NED in transurethral resection
      of the prostate (TURP) samples from 53 patients with prostate cancer was
      investigated by immunocytochemistry using polyclonal rabbit immunoglobin G (IgG)
      against chromogranin A (CgA). Changes in NED with time were determined by a
      manual semiquantitative cell counting method. RESULTS: During androgen withdrawal
      therapy, 21 tumors (40%) displayed increased NED concomitant with histopathologic
      tumor progression, whereas 29 carcinomas (55%) showed no change in NED status.
      However, a majority of the histopathologically unchanged tumors displayed marked
      NED at the first TURP and an increase in NED was by definition not possible. In
      only 3 cases (5%) was a decrease in NED observed with time. CONCLUSIONS: Androgen
      ablation therapy may be a contributing factor to the increase in NED of prostatic
      adenocarcinoma with time, and our findings imply that androgen withdrawal therapy
      enhances the selection and progression of NED, androgen-independent tumor cells.

PMID- 9586612
TI  - Prostate cancer in Denmark: a 50-year population-based study.
AB  - OBJECTIVES: To review the trends in prostate cancer (PC) incidence and mortality
      rates in Denmark during a 50-year period. METHODS: A population-based register
      study was performed of all new cases of PC recorded in the Danish Cancer Registry
      from 1943 to 1992. RESULTS: The age-standardized incidence rate for PC increased
      from 11.5/100,000 in 1943 to 1947 to 30.9/100,000 in 1988 to 1992. Age-specific
      incidence rates increased in all age groups over 50 years of age. Mortality rates
      increased from 13.5/100,000 in 1953 to 1957 to 17.8/100,000 in 1988 to 1992. No
      major changes in the distribution of age, stage at the time of diagnosis, or in
      diagnostic procedures were found, indicating that the observed change in
      incidence rates was not caused by attempted early detection or changes in
      diagnostic strategy. CONCLUSIONS: Our data suggest that the increased PC
      incidence observed during the period of cancer registration in Denmark represents
      a true increase in the number of patients with clinical PC.

PMID- 9586613
TI  - Transition zone index as a risk factor for acute urinary retention in benign
      prostatic hyperplasia.
AB  - OBJECTIVES: To examine the efficacy of various parameters obtained by transrectal
      ultrasonography (TRUS) as predictors of the onset of acute urinary retention in
      patients with benign prostatic hyperplasia (BPH). METHODS: From April 1993 to
      March 1997, 331 men aged 51 to 84 years with symptoms of BPH were enrolled in
      this study. Among them, 64 patients presented to our clinic because of acute
      urinary retention. TRUS was used to calculate the transition zone (TZ) volume,
      the transition zone index (TZ index = TZ volume/total prostate volume), the total
      prostate volume, and presumed circle area ratio (PCAR). To compare the usefulness
      of the various indices, the area under the receiver-operator characteristic (ROC)
      curve was calculated for each index. RESULTS: There were significant differences
      in the American Urological Association (AUA) symptom score, total prostate
      volume, TZ volume, TZ index, and PCAR between patients with and without acute
      urinary retention, but no significant differences in age and quality of life
      score. In patients with acute urinary retention, the area under the ROC curve was
      0.924 for the TZ index, 0.834 for the TZ volume, 0.753 for the PCAR, 0.684 for
      the total prostate volume, and 0.628 for the AUA symptom score. CONCLUSIONS: The
      TZ index is an accurate predictor of acute urinary retention in patients with BPH
      and may be a useful method for deciding between surgical intervention and
      antiandrogen treatment.

PMID- 9586614
TI  - Mechanisms of incontinence and retention after orthotopic neobladder diversion.
AB  - OBJECTIVES: To define the mechanism of incontinence and retention after
      orthotopic neobladder diversion. METHODS: The results of urodynamic and
      endoscopic evaluations were assessed in 19 patients (15 men and 4 women). Mean
      age and postoperative follow-up were 58.3 years and 19.6 months, respectively.
      Seventeen patients (15 men, 2 women) presented with the sole complaint of
      nocturnal incontinence, and 2 women presented with retention. Evaluations
      included voiding and continence history, pelvic examination (for women), postvoid
      residual, uroflowmetry, triple-lumen video-urodynamic study, and
      cystourethroscopy. RESULTS: Among patients with incontinence, 11 (65%) were found
      to have a primary failure-to-store problem as a result of either reservoir or
      sphincter failure. Four patients (24%) had a primary failure-to-empty problem,
      and 2 (11%) had features of both. The predominant etiology of voiding difficulty
      was the inability to relax the external urethral sphincter adequately during
      Valsalva's maneuver. Of the 2 women who presented with retention, one had
      obstructing mucosal folds at the neobladder opening and both demonstrated
      anterior vaginal wall prolapse on pelvic examination. CONCLUSIONS: The mechanism
      of incontinence and retention after orthotopic neobladder diversion can vary.
      Carefully performed urodynamic and endoscopic assessments can define the
      underlying etiology and may serve as a guide for proper treatment selection.

PMID- 9586615
TI  - A controlled trial of levofloxacin and lomefloxacin in the treatment of
      complicated urinary tract infection.
AB  - OBJECTIVES: The efficacy and safety of levofloxacin and lomefloxacin in
      complicated urinary tract infections (UTIs) were compared in a randomized, open
      label, multicenter study. METHODS: Outpatients were randomized to receive
      levofloxacin (250 mg once daily) for 7 to 10 days or lomefloxacin (400 mg once
      daily) for 14 days. Three hundred thirty-six patients (171 with levofloxacin, 165
      with lomefloxacin) were evaluable for microbiologic efficacy, and 461 patients
      (232 with levofloxacin, 229 with lomefloxacin) for safety. RESULTS: The overall
      microbiologic eradication rate of pathogens was 95.5% (168 of 176) for
      levofloxacin and 91.7% (154 of 168) for lomefloxacin. Eradication rates with
      respect to patients were 95.3% (163 of 171) and 92.1% (152 of 165) for
      levofloxacin and lomefloxacin, respectively. At the 5 to 9-day post-therapy
      visit, symptoms were completely resolved in 84.8% of levofloxacin-treated
      patients and were decreased in 8.2% (93.0% clinical success). Among the
      lomefloxacin-treated patients, complete resolution was seen in 82.4%, with
      decreased symptoms in 6.1% (88.5% clinical success). Drug-related adverse events
      (AEs) were reported by 10 (2.6%) and 18 (5.2%) levofloxacin- and lomefloxacin
      treated patients, respectively. Compared with levofloxacin-treated patients, more
      lomefloxacin-treated patients experienced photosensitivity reactions (3 [1.3%]
      versus 0) and dizziness (2 [0.9%] versus 0). Nausea (3 [1.3%] versus 1 [0.4%])
      was more frequent in the levofloxacin-treated group. Six patients in each
      treatment group had a gastrointestinal AE (1.7%); rash was reported more
      frequently with lomefloxacin (4 patients [0.4%]) than with levofloxacin (1
      patient [0.4%]). Discontinuation because of AEs was observed in 8 (3.4%)
      levofloxacin- and 14 (6.1%) lomefloxacin-treated patients. CONCLUSIONS: Once
      daily levofloxacin is as effective as and has a superior tolerability profile
      than lomefloxacin in the treatment of complicated UTIs.

PMID- 9586616
TI  - Urethrography and cavernosography imaging in a small series of penile fractures:
      a comparison with surgical findings.
AB  - OBJECTIVES: To compare our results of preoperative corporal cavernosography and
      retrograde urethrography in penile fractures with the clinical and intraoperative
      findings. METHODS: From January to October 1996, 7 cases of penile fracture were
      diagnosed at our inner city trauma center. All cases were associated with sexual
      activity and patients underwent preoperative retrograde urethrography and corpus
      cavernosography with immediate surgical intervention. RESULTS: We found that 2
      patients who presented with blood at the meatus had intact urethras, whereas 2 of
      the 3 patients who had urethral lacerations did not have a bloody meatus. In 2
      cases the urethrogram and cavernosogram revealed lacerations that were not
      initially detected surgically. However, in another 2 cases, the urethrogram and
      cavernosogram were falsely negative. Two of the seven corporal fractures were
      bilateral and five were unilateral. CONCLUSIONS: On the basis of this small
      sample, it appears that preoperative cavernosography and retrograde urethrography
      may show additional sites of tears in the corpora and urethra because hematoma
      formation may mask some ruptures. However, the presence or absence of a bloody
      meatus may not necessarily correlate with the status of the urethra, and the
      urologist also should be wary of a false-negative imaging study. We suggest that
      all cases of penile fracture be explored surgically, but preferably by a
      subcoronal degloving incision that allows careful examination of the urethra and
      corpora. Results of a larger series may determine if the routine use of these
      imaging modalities is justified intraoperatively.

PMID- 9586617
TI  - Use of intralesional verapamil to dissolve Peyronie's disease plaque: a long-term
      single-blind study.
AB  - OBJECTIVES: Multiple conservative therapies for the treatment of Peyronie's
      disease have been offered with variable and poor response rates. Calcium channel
      blockers have been shown in vitro and in vivo to inhibit secretion and synthesis
      of extracellular matrix, including collagen, glycosaminoglycans, and fibronectin,
      as well as causing increased collagenase and anti transforming growth factor-beta
      activity. Calcium antagonists, including verapamil, are effective in stimulating
      the remodeling and degradation of extracellular matrix in tissue by altering the
      metabolic pathways of fibroblasts. Recently, a pilot study (1994) showed
      preliminary promising results in treating plaque caused by Peyronie's disease.
      This randomized single-blind placebo-based study (1994 to 1996) was undertaken to
      confirm the hypothesis. METHODS: In this randomized single-blind study, 14
      patients completed the study and were divided into two groups: the verapamil
      treatment group (n = 7) or the control saline group (n = 7). Verapamil or saline
      was injected directly into the Peyronie's plaque once a week for 6 months.
      Patients were evaluated before and after treatment with duplex ultrasound to
      confirm the extent of the lesion and to measure volume of the plaque, and by
      interview and mailed questionnaire 3 months after treatment. Patients being
      treated with oral calcium antagonists were excluded from the study. RESULTS: A
      decreased plaque volume was measured in 57% of the verapamil-treated men versus
      28% in the control group (P <0.04). Penile curvature demonstrated an improvement
      trend of 37.71 +/- 9.3 degrees to 29.57 +/- 7.3 degrees in the verapamil-treated
      patients, but the difference was not significant (P <0.07). Plaque softening was
      noted in all patients treated with verapamil. There was significant objective
      improvement in plaque-associated penile narrowing in all patients in the
      verapamil group. Subjective plaque-associated erectile dysfunction (quality of
      erection) showed improvement in 42.87% of the verapamil group versus none in the
      control group (P <0.02). There was no local or systemic toxicity except for an
      occasional ecchymosis/bruise at the injection site. After a positive clinical
      response, plaque size, penile angulation, and symptoms continued to improve.
      Decrease in plaque size was noted in each of the responders in the first 3
      months. CONCLUSIONS: This randomized single-blind study suggests that
      intralesional injection of calcium channel blocker may be a reasonable approach
      in some selected patients for the treatment of Peyronie's disease with
      noncalcified plaque and penile angulation of less than 30 degrees. Patients whose
      plaque failed to respond to intralesional verapamil therapy within 3 months or
      whose angulation was greater than 30 degrees at presentation were more likely to
      benefit from surgery.

PMID- 9586618
TI  - Unusual complications of the vacuum erection device.
AB  - OBJECTIVES: The vacuum erection device (VED) is usually well tolerated and very
      effective for patients with erectile dysfunction. When used correctly, VEDs carry
      low morbidity and few recognized complications. We report on 5 patients who
      developed unusual complications associated with VED use, including two previously
      unreported complications of urethral bleeding and capture of scrotal tunica
      within the penile shaft. METHODS: Patient 1: a 38-year-old diabetic man with
      significant peripheral neuropathy and an 8-year history of erectile dysfunction
      developed penile skin necrosis at the ring site after leaving the penile ring on
      for an excessive length of time (6 hours). Patient 2: a 76-year-old diabetic man
      who used a VED correctly for 3 months developed severe urethral bleeding. Patient
      3: a 75-year-old diabetic man who enjoyed satisfactory erections with a VED for
      14 months developed a 3 x 3-cm penile cystic mass located on the proximal right
      side of the penile shaft. This mass was not present in the flaccid state and was
      seen only with VED use. Patient 4: a 65-year-old man developed Peyronie's disease
      after 4 years of correct VED use. Patient 5: a 62-year-old man with neurogenic
      impotence following a radical prostatectomy developed penile ecchymoses acutely
      following placement of a smaller constriction ring. He subsequently developed a
      dorsal penile plaque with mild dorsal curvature. RESULTS: Patient 1 did well with
      local skin care and no longer uses a VED. Patient 2 underwent cystoscopy and was
      found to have prominent urethral vessels (varicosities) in the midurethra,
      compared with a normal cystoscopy 9 months previously. This patient no longer
      uses a VED and now denies any urethral bleeding at 15-month follow-up. Patient 3
      underwent corpora cavernosography and contrast injection of the cystic mass.
      These radiographic studies showed that the mass did not communicate with either
      corpora cavernosa or the corpus spongiosum. A retrograde urethrogram failed to
      show a urethral diverticulum. The patient was surgically explored, and the penile
      cystic mass was found to be scrotal tunica vaginalis. Subsequently, a hydrocele
      repair was performed, yet postoperatively the patient developed testicular
      migration into the ipsilateral penile shaft. Testicular fixation was not feasible
      secondary to a childhood herniorrhaphy, and an orchiectomy was performed. Patient
      4 underwent implantation of a penile prosthesis and is doing well at 3-year
      follow-up. Patient 5 experiences mild dorsal penile curvature with erections
      induced by transurethral prostaglandin E1. The penile curvature does not
      interfere with intercourse and will be managed conservatively. CONCLUSIONS: We
      describe unusual side effects associated with VEDs. Although thousands of men use
      VEDs successfully and without morbidity, the urologist must be aware of unusual
      complications associated with VED use.

PMID- 9586619
TI  - Adenocarcinoma arising within a testicular metastasis.
AB  - Teratoma with malignant transformation is defined as the emergence of a non-germ
      cell tumor from a teratoma. Although extremely rare in extraovarian sites, cases
      have been reported that involve primary extragonadal germ cell tumors with
      transformation to variants of sarcoma. We report a 54-year-old man who was found
      to have adenocarcinoma arising within a mature teratomatous retroperitoneal
      metastasis 15 years after treatment of a nonseminomatous testicular germ cell
      tumor. The tumor was successfully excised and he remains without evidence of
      disease.

PMID- 9586620
TI  - Multiocular cystic renal cell carcinoma: implications for nephron sparing
      surgery.
AB  - Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon type of cystic
      renal neoplasm with characteristic histologic findings and a good prognosis.
      Three cases are reported. One case involves enucleation of an MCRCC in a kidney
      donor with a 10-year follow-up and no recurrence in the transplant recipient.
      Nephron sparing surgery should be considered when the diagnosis of MCRCC is
      suspected preoperatively and confirmed intraoperatively.

PMID- 9586621
TI  - Penile implant for intractable priapism associated with sickle cell disease.
AB  - Intractable, therapy-resistant priapism in a patient with sickle cell disease is
      presented. The patient was managed with insertion of an inflatable penile
      prosthesis. He consequently maintained potency and remains free of priapitic
      episodes. To our knowledge, immediate penile prosthesis insertion for management
      of priapism has not been reported. We discuss the indications and advantages of
      this approach and review the current literature.

PMID- 9586622
TI  - Intracavernous pressure responses to physical and electrical stimulation of the
      cavernous nerve in rats.
AB  - OBJECTIVES: To better define the techniques of nerve-sparing prostate dissection
      that would result in preservation of erectile function, we characterize the
      effects of physical pressure on the prostate and cavernous nerve, electrical
      stimulation of the cavernous nerve, and pharmacologic manipulations on
      intracavernous pressure (ICP) in normal and diabetic rats. METHODS: Fischer-34
      rats, both normal and diabetic, underwent dissections that isolated the cavernous
      bodies and cavernous nerves. Cavernous body pressures were characterized during
      surgical manipulation, during electrical stimulation of the cavernous nerves, and
      following papaverine hydrochloride injection. RESULTS: In normal rats, baseline
      cavernous pressures ranged from 5 to 15 cm H2O (mean 12.29). In diabetic rats,
      the baseline pressure was significantly lower (3 to 7.5 cm H2O). Lateral nerve
      displacement caused ICP to rise to approximately 35 cm H2O in normal rats, but
      only to 20 cm H2O in diabetic rats. Electrostimulation resulted in cavernous
      pressure increases of 10-fold from baseline in normal rats and sevenfold from
      baseline in diabetic rats. ICPs were not disturbed appreciably with nerve-sparing
      dissection techniques. Neurotomy resulted in declines in baseline cavernous
      pressures in all rats. Electrostimulation of the distal end of a severed nerve
      resulted in pressure rises to 50% of those observed in rats with intact cavernous
      nerves. Intracavernous papaverine injection before or after nerve stimulation
      masked subsequent (expected) pressure changes. CONCLUSIONS: A change in cavernous
      pressure is a sensitive indicator of cavernous nerve manipulation. Both cavernous
      pressure measurements and electrostimulation of cavernous nerves may aid surgeons
      during radical prostatectomy.

PMID- 9586623
TI  - Impact of the expression of epidermal growth factor, transforming growth factor
      alpha, and epidermal growth factor receptor on the prognosis of superficial
      bladder cancer.
AB  - OBJECTIVES: To investigate the correlation of epidermal growth factor receptor
      (EGFR) expression and its ligands EGF and transforming growth factor-alpha (TGF
      alpha) with disease outcome in a cohort of patients with superficial bladder
      cancer. METHODS: Tumor samples of 21 patients with transitional cell carcinoma of
      the bladder were analyzed by immunohistochemistry for expression of EGFR, EGF,
      and TGF-alpha. Disease-related events were recorded during a routine clinical
      follow-up and analyzed for possible correlation with the expression status of the
      above-mentioned proteins. RESULTS: All Stage pT1 transitional cell carcinomas
      expressed EGFR, and 10 of 21 (48%) tumors showed focal areas of strong EGF and/or
      TGF-alpha expression. Of these, 80% with EGF positivity (8 of 10) had
      recurrences, whereas only 9% of patients without EGF staining (1 of 11) did so.
      The same pattern was observed with TGF-alpha. A strong association was confirmed
      between EGF/TGF-alpha positivity and tumor recurrence (P <0.005). We also found
      that EGF and TGF-alpha were expressed in stroma and/or around the vessels of
      tumor tissue in 48% and 38% of the tumors, respectively. No association was found
      between the recurrence rate/vascular invasion and the stromal/vascular wall
      expression of the growth factors. CONCLUSIONS: Expression of EGF and TGF-alpha is
      correlated with tumor recurrence. Also, there is the ability of vessel walls to
      express EGF and TGF-alpha in superficial bladder cancer. Further clarification of
      the impact of this expression on angioinvasion of tumor cells may be helpful in
      understanding the nature of local invasion and metastasis.

PMID- 9586624
TI  - Effect of estrogen withdrawal on nitric oxide synthase expression and apoptosis
      in the rat vagina.
AB  - OBJECTIVES: The physiology of the female sexual response and its molecular
      mediators remain poorly understood. Nitric oxide (NO) is synthesized in neurons
      and is a potent relaxor of vascular and nonvascular smooth muscle. In this study,
      we hypothesize that vaginal atrophy and declining sexual function during
      menopause may be NO dependent. Using the rat as an experimental model, we
      examined the expression and topologic localization of vaginal NO synthase (NOS)
      and the concomitant induction of apoptosis under normal and estrogen-depleted
      conditions. METHODS: Thirty rats were categorized into six groups on the basis of
      phase of the estrous cycle or estrogen status after oophorectomy. The expression
      and cellular localization of NOS was examined in frozen sections using specific
      antibodies against neuronal (N-NOS) and endothelial NOS (E-NOS). Apoptotic cells
      were identified in situ using the terminal transferase technique (TUNEL).
      Trichome staining was performed in all specimens to determine smooth
      muscle/collagen ratios. RESULTS: N-NOS immunoreactivity was localized to nerve
      fibers supplying vaginal smooth muscle, perivascular nerve plexuses, and lamina
      propria. E-NOS was localized to vascular endothelium and perivascular smooth
      muscle fibers. Both E-NOS and N-NOS expression in intact cycling animals was
      highest during proestrous and lowest during metestrous. After oophorectomy,
      levels of both N-NOS and E-NOS declined substantially compared with those of
      intact animals, and there was a parallel induction of apoptosis. Estrogen
      withdrawal also resulted in increased vaginal atrophy, intramural collagen
      accumulation, and perivascular wall thickening, as identified by trichome
      staining. Estrogen replacement resulted in a significant increase in E-NOS and N
      NOS expression, as well as diminished apoptosis and vaginal atrophy. CONCLUSIONS:
      This cellular distribution of NOS in the rat vagina suggests that NO may modulate
      both vaginal blood supply and vaginal smooth musculature. Estrogen appears to
      play a critical role in concomitantly regulating vaginal NOS expression and
      apoptosis in nerves, smooth muscle, vascular endothelium, and epithelium of the
      rat vagina. These findings may have significant clinical implications for the
      pathophysiology of postmenopausal female sexual dysfunction.

PMID- 9586625
TI  - Expression of prostatic factors measured by reverse transcription polymerase
      chain reaction in human papillomavirus type 18 deoxyribonucleic acid immortalized
      prostate cell lines.
AB  - OBJECTIVES: To investigate expression of the prostatic markers prostate-specific
      antigen (PSA), prostate-specific membrane antigen (PSM), and the androgen
      receptor (AR) after human papillomavirus (HPV) type 18 deoxyribonucleic acid
      (DNA) transfection and subsequent immortalization of human prostate epithelial
      cells. METHODS: Recently, two human prostate epithelial cell lines were
      established by HPV transformation: PZ-HPV-7, derived from normal peripheral zone
      (PZ) tissue, and CA-HPV-10, derived from high Gleason grade adenocarcinoma.
      Expression of PSA was studied by the reverse transcription polymerase chain
      reaction (RT-PCR), because in preliminary studies using immunocytochemistry and
      Northern blotting, no PSA expression was found. PSM was analyzed by RT-PCR and
      nested RT-PCR. These analyses included primary human prostate cell strains.
      Furthermore, androgen-supplemented methylthiazol tetrazolium (MTT) growth assays
      were performed and expression of AR was studied by immunocytochemistry. Prostate
      carcinoma cell lines LNCaP and PC-346C were included as positive controls and
      breast carcinoma cell line MCF-7 as a negative control. RESULTS: Both cell lines
      exhibited low levels of RNA for PSA and PSM in comparison with cell lines LNCaP
      and PC-346C. AR expression by immunocytochemistry was negative using monoclonal
      antibody F39.4 and polyclonal antibody SP-197. In an androgen-supplemented
      environment, growth rates of both HPV immortalized cell lines were not stimulated
      in contrast to LNCaP. CONCLUSIONS: RNA transcripts of PSA and PSM were detected
      by RT-PCR in HPV immortalized prostate epithelial cell lines PZ-HPV-7 and CA-HPV
      10. The expression of prostate-specific markers may further validate the utility
      of this stepwise transformation model of human prostate carcinogenesis.

PMID- 9586626
TI  - Prostatic stromal cell phenotype is directly modulated by norepinephrine.
AB  - OBJECTIVES: To evaluate the response of prostatic stromal cells in vitro to the
      action of the agonist norepinephrine and to examine the role of cell density in
      this response. METHODS: Stromal cells isolated from transurethral chippings of
      patients with benign prostatic hyperplasia (BPH) were seeded onto tissue culture
      dishes either at high density (9 x 10(3) cells/cm2) or at low density (1.5 x
      10(3) cells/cm2). Norepinephrine was added at concentrations in the range of 2.5
      to 50 microM. Cells were harvested at the moment of confluence, labeled with
      monoclonal antibodies to four cytoskeletal proteins, and analyzed by flow
      cytometry. RESULTS: Sparsely plated stromal cells showed a consistent biphasic
      response in which a small fall in immunofluorescence occurred in the range of 5
      to 15 microM norepinephrine but was thereafter followed by a progressive rise in
      fluorescence to 50 microM, indicating increased expression of smooth-muscle
      associated cytoskeletal proteins. The shape of flow-cytometric frequency
      distribution histograms for smooth-muscle myosin, desmin, and talin suggested
      that all mesenchymal cells in the stromal cultures were similarly modulated by
      norepinephrine. However, the effect on smooth-muscle actin was different in that
      a subpopulation of hyperreactive cells was identified. Densely plated stromal
      cells did not show a similar biphasic response to norepinephrine but instead
      demonstrated an overall downward trend, indicating a progressively diminished
      expression of these cytoskeletal proteins. CONCLUSIONS: Norepinephrine
      stimulation directly modulates BPH-derived prostatic stromal cells toward a
      differentiated smooth-muscle phenotype as evidenced by increased expression of
      cytoskeletal proteins. The effect of norepinephrine on cultures is cell-density
      dependent, suggesting that intercellular communication is an important factor in
      coordinating the differentiation responses. This study has revealed a specific
      interaction between physical and humoral stimuli, which influences in part the
      phenotype of prostatic stromal cells. Such interaction is likely to determine the
      development of clinical BPH, and also the response of any individuals following
      therapeutic intervention using selective alpha-adrenergic blockade.

PMID- 9586628
TI  - Type III statistical error.

PMID- 9586627
TI  - The invention of the modern uroflowmeter by Willard M. Drake, Jr at Jefferson
      Medical College.
AB  - The uroflowmeter is perhaps the most important and certainly the most commonly
      used urodynamic instrument currently employed in urologic practice. The modern
      uroflowmeter was invented by Willard M. Drake, Jr., in 1946 at the Jefferson
      Medical College. The original manuscript, entitled "The uroflometer: an aid to
      the study of the lower urinary tract," appeared in Journal of Urology in 1948.
      Drake obtained a US patent for the device, entitled "Uroflometer," in 1953. The
      flowmeter, originally manufactured by van Beek Industries, was more recently
      manufactured and distributed by Grewe Plastics. Drake is now retired and living
      in Nacogdoches, Texas.

PMID- 9586629
TI  - A tale of two T cells.

PMID- 9586630
TI  - Networking Rho family GTPases in lymphocytes.

PMID- 9586631
TI  - Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax
      peptide complex using different TCR amino acids.
AB  - The three-dimensional structure of a human alphabeta T cell receptor (TCR), B7,
      bound to the HLA-A2 molecule/HTLV-1 Tax peptide complex was determined by x-ray
      crystallography. Although different from the A6 TCR, previously studied, in 16 of
      the 17 residues that contact HLA-A2/Tax, the B7 TCR binds in a similar diagonal
      manner, only slightly tipped and rotated, relative to the A6 TCR. The structure
      explains data from functional assays on the specificity differences between the
      B7 and A6 TCRs for agonist, partial agonist, and null peptides. The existence of
      a structurally similar diagonal binding mode for TCRs favors mechanisms based on
      the formation of geometrically defined supramolecular assemblies for initiating
      signaling.

PMID- 9586632
TI  - Alanine scanning mutagenesis of an alphabeta T cell receptor: mapping the energy
      of antigen recognition.
AB  - The T cell receptor (TCR) from the alloreactive T lymphocyte 2C recognizes a
      nonamer peptide QL9 complexed with the MHC class I molecule H2-Ld. Forty-two
      single-site alanine substitutions of the 2C TCR were analyzed for binding to
      QL9/Ld and anti-TCR antibodies. The results provided a detailed energy map of T
      cell antigen recognition and indicated that the pMHC and clonotypic antibody
      epitopes on the TCR were similar. Although residues in each Valpha and Vbeta CDR
      are important in binding pMHC, the most significant energy for the TCR/QL9/Ld
      interaction was contributed by CDRs 1 and 2 of both alpha and beta chains. The
      extent to which the individual energy contributions are directed at class I
      helices or peptide was also assessed.

PMID- 9586633
TI  - The developmental fate of T cells is critically influenced by TCRgammadelta
      expression.
AB  - Differentiation of gammadelta and alphabeta T cells from a common precursor cell
      depends on productive rearrangement and expression of TCRgammadelta or TCRbeta
      genes, but whether it is an instructive or a stochastic mechanism that is
      responsible for this process is unclear. We report that expression of the
      productively rearranged TCRgamma transgene competitively inhibits alphabeta
      thymocyte development under conditions where TCRbeta gene rearrangement is
      limiting. The status of TCRdelta gene rearrangements in the remaining alphabeta
      lineage cells indicates that the effect is mediated by the intact gammadelta
      receptor. Paradoxically, in TCRbeta-/- mice, gammadelta receptor expression can
      also drive differentiation of some alphabeta-lineage cells. To resolve this
      paradox, we provide evidence for a minor population of gammadelta-dependent
      alphabeta-lineage cells in normal mice. The results indicate that the T cell
      lineage commitment process is either error-prone or stochastic.

PMID- 9586634
TI  - A role for FADD in T cell activation and development.
AB  - FADD is a cytoplasmic adapter molecule that links the family of death receptors
      to the activation of caspases during apoptosis. We have produced transgenic mice
      expressing a dominantly interfering mutant of FADD, lacking the caspase
      dimerizing death effector domain, as well as mice overexpressing the poxvirus
      serpin, CrmA, an inhibitor of caspases downstream of FADD. While thymocytes from
      either line of mice were completely protected from CD95-dependent cytotoxicity,
      neither transgene afforded protection from apoptosis induced during thymocyte
      selection and neither led to the lymphoproliferative disorders associated with
      deficiencies in CD95. However, in FADD dominant negative (FADDdd) mice, early
      thymocyte development was retarded and peripheral lymphocyte pools were devoid of
      normal populations of T cells. We show that thymocytes and peripheral T cells
      from FADDdd display signaling anomalies, implying that FADD plays a previously
      uncharacterized role in T cell development and activation.

PMID- 9586635
TI  - Granzyme B directly and efficiently cleaves several downstream caspase
      substrates: implications for CTL-induced apoptosis.
AB  - Caspase-mediated proteolysis of downstream substrates is a critical element of
      the execution pathway common to all forms of apoptosis studied to date. While
      this caspase-dependent pathway is activated during cytotoxic lymphocyte granule
      induced cell death, recent studies have also provided evidence for caspase
      independent pathways. However, the mechanisms mediating these additional pathways
      have not been defined. The current study demonstrates that DNA-PKcs and NuMA are
      directly and efficiently cleaved by granzyme B in vitro and in vivo, generating
      unique substrate fragments not observed during other forms of apoptosis. This
      direct, caspase-independent ability of granzyme B to cleave downstream death
      substrates constitutes an apoptotic effector mechanism that is insensitive to
      inhibitors of the signaling or execution components of the endogenous apoptotic
      cascade.

PMID- 9586636
TI  - Toso, a cell surface, specific regulator of Fas-induced apoptosis in T cells.
AB  - Fas is a surface receptor that can transmit signals for apoptosis. Using
      retroviral cDNA library-based functional cloning we identified a gene, toso, that
      blocks Fas-mediated apoptosis. Toso expression was confined to lymphoid cells and
      was enhanced after cell-specific activation processes in T cells. Toso appeared
      limited to inhibition of apoptosis mediated by members of the TNF receptor family
      and was capable of inhibiting T cell self-killing induced by TCR activation
      processes that up-regulate Fas ligand. We mapped the effect of Toso to inhibition
      of caspase-8 processing, the most upstream caspase activity in Fas-mediated
      signaling, potentially through activation of cFLIP. Toso therefore serves as a
      novel regulator of Fas-mediated apoptosis and may act as a regulator of cell fate
      in T cells and other hematopoietic lineages.

PMID- 9586637
TI  - A poxvirus-encoded semaphorin induces cytokine production from monocytes and
      binds to a novel cellular semaphorin receptor, VESPR.
AB  - The vaccinia virus A39R protein is a member of the semaphorin family. A39R.Fc
      protein was used to affinity purify an A39R receptor from a human B cell line.
      Tandem mass spectrometry of receptor peptides yielded partial amino acid
      sequences that allowed the identification of corresponding cDNA clones. Sequence
      analysis of this receptor indicated that it is a novel member of the plexin
      family and identified a semaphorin-like domain within this family, thus
      suggesting an evolutionary relationship between receptor and ligand. A39R up
      regulated ICAM-1 on, and induced cytokine production from, human monocytes. These
      data, then, describe a receptor for an immunologically active semaphorin and
      suggest that it may serve as a prototype for other plexin-semaphorin binding
      pairs.

PMID- 9586638
TI  - Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a
      cryptic sorting signal in MHC I molecules.
AB  - The surface expression of MHC I is reduced in HIV-infected cells. We show that
      the Nef protein affects the intracellular sorting of HLA-A and -B molecules. In
      the presence of Nef, these proteins accumulate in the Golgi and colocalize with
      clathrin-coated vesicles. MHC I modulation relies on a tyrosine-based sorting
      signal located in the cytoplasmic domain of HLA-A and -B heavy chains. This
      cryptic sorting signal becomes operative only in the presence of Nef. Nef
      interacts with the medium (mu) subunit of AP adaptor complexes involved in the
      recognition of tyrosine-based sorting signals, likely facilitating the connection
      between MHC I and the clathrin-dependent sorting machinery.

PMID- 9586639
TI  - Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a
      biochemical pathway regulating BCR signaling and selection.
AB  - A B lymphocyte hyperactivity syndrome resembling systemic lupus erythematosus
      characterizes mice lacking the src-family kinase Lyn. Lyn is not required to
      initiate B cell antigen receptor (BCR) signaling but is an essential inhibitory
      component. lyn-/- B cells have a delayed but increased calcium flux and
      exaggerated negative selection responses in the presence of antigen and
      spontaneous hyperactivity in the absence of antigen. As in invertebrates, genetic
      effects of loci with only one functional allele can be used to analyze signaling
      networks in mice, demonstrating that negative regulation of the BCR is a complex
      quantitative trait in which Lyn, the coreceptor CD22, and the tyrosine
      phosphatase SHP-1 are each limiting elements. The biochemical basis of this
      complex trait involves a pathway requiring Lyn to phosphorylate CD22 and recruit
      SHP-1 to the CD22/BCR complex.

PMID- 9586640
TI  - SHIP modulates immune receptor responses by regulating membrane association of
      Btk.
AB  - Membrane recruitment of SHIP is responsible for the inhibitory signal generated
      by FcgammaRIIB coligation to the BCR. By reducing the level of PIP3, SHIP
      regulates the association of the tyrosine kinase Btk with the membrane through PH
      domain-phosphoinositol lipid interactions. Inhibition of BCR signaling by either
      FcgammaRIIB coligation, membrane expression of SHIP, or inhibition of P13K,
      conditions which result in decreased levels of PIP3, is suppressed by the
      expression of Btk as a membrane-associated chimera. Conversely, increasing PIP3
      levels by deletion of SHIP results in increased Btk association with the membrane
      and hyperresponsive BCR signaling. These results suggest a central role for PIP3
      in regulating the B cell stimulatory state by modulating Btk localization and
      thereby calcium fluxes.

PMID- 9586641
TI  - Allergy-associated FcRbeta is a molecular amplifier of IgE- and IgG-mediated in
      vivo responses.
AB  - A role for the Fc receptor beta chain (FcRbeta) in the pathogenesis of allergy
      has been suggested by genetic studies. FcRbeta is a subunit common to the high
      affinity IgE (FcepsilonRI) and low-affinity IgG (FcgammaRIII) receptors, both of
      which contribute to the initiation of allergic reactions. Current in vitro data
      suggest that FcRbeta can function as either a positive or negative regulator,
      leaving a mechanistic explanation for its association with the development of
      atopy unclear. To address this controversy, we have generated novel mouse models
      relevant to human Fc receptor function. Analysis of FcepsilonRI- and FcgammaRIII
      dependent responses in these mice provides unequivocal genetic evidence that
      FcRbeta functions as an amplifier of early and late mast cell responses and,
      remarkably, in vivo anaphylactic responses.

PMID- 9586643
TI  - The Amsterdam Cohort Studies on HIV infection and AIDS.
AB  - The Amsterdam Cohort Studies (ACS) on HIV infection and AIDS are a collaborative
      effort between the Academic Medical Centre (departments of Retrovirology and
      Internal Medicine), the Central Laboratory of Netherlands Red Cross Blood
      Transfusion Service, and the Amsterdam Municipal Health Service. The aims of the
      ACS are to study the prevalence, incidence, and risk factors for HIV infection
      and AIDS, to study the natural history of HIV-1 infection, to carry out
      intervention studies, and to evaluate prevention programs. Many of the questions
      originally addressed by the ACS have now been answered, providing valuable
      insights into the prevalence, incidence, and risk of HIV infection. The emphasis
      of the study is now shifting toward the natural history of HIV-1 (HIV-2 being
      extremely rare). Several interventional studies have also been carried out,
      although this was not the original aim of the ACS.

PMID- 9586644
TI  - Studies of antiretroviral therapy in the Multicenter AIDS Cohort Study.
AB  - The Food and Drug Administration has been increasingly reliant on surrogate end
      points to fast-track the licensing of antiretroviral agents. As a result,
      critical information, such as long-term adverse events, clinical progression
      rates, survival, and development of resistance, are not available before
      licensure. Therefore, phase IV studies conducted in large community- and/or
      clinic-based cohorts will become essential to fill in the gaps in the clinical
      knowledge base for many of these drugs, and observational cohort studies of HIV
      infected patients have been used to address many of these questions. In addition
      to studies of antiretroviral impact on adverse events and outcomes, such cohorts
      can provide valuable data on utilization patterns, physician prescribing
      patterns, and the important issue of patient compliance with increasingly
      complicated drug regimens.

PMID- 9586645
TI  - Determinants of progression to AIDS in HIV-infected individuals: an update from
      the Italian Seroconversion Study.
AB  - The Italian Seroconversion Study (ISS) involves 16 major HIV-treatment centers
      across Italy and about 1,200 individuals. These individuals were HIV-negative
      less than 2 years before the first positive test and seroconverted between 1980
      and 1994. The majority were infected through i.v. drug use (56%), male-to-male
      sex (25%), and heterosexual contact (7%). For each end point, crude and adjusted
      relative hazards were calculated using standard survival techniques such as
      Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression
      models. Autoregression models were used to describe CD4 cell reductions.
      Objectives were as follows: to estimate HIV disease progression rates; to assess
      whether there are differences in the rate of development of severe
      immunosuppression, AIDS, and death according to age, gender, and exposure
      category; to identify co-factors and predictors of disease progression; and to
      evaluate the clinic-based population "effect" of antiretroviral treatment. The
      risk for developing AIDS among individuals in the ISS cohort was less than 50% by
      10 years after HIV seroconversion. Using univariate analysis, more rapid
      progression was found for older individuals than for younger individuals and for
      homosexual men compared with those in other exposure categories. No difference
      between men and women was observed. After adjusting for age, differences among
      exposure groups disappeared. Individuals with a history of acute HIV disease were
      more likely to develop AIDS than other seroconverters. Co-infection with HCV and
      HTLV-II did not accelerate progression to AIDS. The cumulative incidence of
      receiving pre-AIDS therapy within 7 years of seroconversion was 49.2% (95% CI
      45.3-53.0). The relative hazards of developing AIDS in patients who started
      treatment with zidovudine (AZT) monotherapy was 0.57 (0.36-0.91) and 0.92 (0.64
      1.33) within the first year and after 1 year from AZT initiation, respectively.
      The effect was greater among homosexual men than among i.v. drug users. In
      conclusion, incident cohort studies may provide accurate information on
      incubation time and co-factors for disease progression. Observational studies may
      also provide useful information about the effect of treatment at the community
      level, which may complement the results of clinical trials.

PMID- 9586646
TI  - The HIV Epidemiology Research Study, HIV Out-Patient Study, and the Spectrum of
      Disease Studies.
AB  - The Division of HIV/AIDS Prevention at the United States Centers for Disease
      Control (CDC) has several observational databases through which it collects
      individual level data that can be used to evaluate the spectrum of HIV-related
      diseases and the utilization of HIV-related health care services. The HIV
      Epidemiology Research Study (HERS) is a multisite, prospective cohort study of
      HIV-infected women and uninfected women reporting HIV risk behavior. By
      interview, clinical examination, specimen collection and storage, laboratory
      testing, and medical record abstraction. HERS is examining the manifestations,
      correlates and predictors of HIV disease in women. In addition to the basic
      visits, a variety of nested studies are under way and several more are planned.
      Three additional observational databases collect individual level data primarily
      through systematic medical record abstraction. The Adult Spectrum of Disease
      (ASD) Study and the Pediatric Spectrum of Disease (PSD) Study collect data from a
      national sample of hospital and clinic medical records. The ASD also has a
      supplementary interview administered to consenting patients with new AIDS
      diagnoses in a subset of their study sites. The HIV Out-Patient Study (HOPS)
      collects data from an electronic charting system on outpatient findings and
      clinical care for patients attending a national sample of infectious disease
      clinics.

PMID- 9586647
TI  - The AIDS Research Consortium of Atlanta database.
AB  - The AIDS Research Consortium of Atlanta (ARCA) is a nonprofit-making community
      based clinical and epidemiologic research unit serving a population of more than
      15,000 patients with HIV infection. This database derives from a core based on
      the Centers for Disease Control Adult Spectrum of Disease Study (ADS), of which
      ARCA is the oldest and largest site. The ARCA includes a variety of data distinct
      from the ADS database and was initiated in recognition of the need for a more
      local registry of patients to address therapeutic approaches and needs
      appropriate for the immediate community. Potential uses for this database include
      evaluation of the natural history of HIV, therapeutic efficacy, and drug safety.

PMID- 9586648
TI  - The Western Australian HIV Cohort Study, Perth, Australia.
AB  - The efficacy of primary prophylactic treatment for opportunistic infections can
      be estimated in an observational cohort study by adjusting for clinical and
      laboratory markers of the immunodeficiency (e.g., oral candidiasis, CD4%,
      lymphocyte cell counts) as time-dependent co-variates (providing that the
      treatment does not directly alter the markers). However, the CD4 cell count
      provides an incomplete measure of the protective immune response, and the
      efficacy of treatment may be underestimated if there is inadequate adjustment for
      the severity of immunodeficiency. Unlike prophylactic therapies, the efficacy of
      which remains relatively constant over time, antiretroviral therapy may produce
      only transient or time-limited benefits. This problem can be minimized by
      allowing the effect of antiretroviral therapy to vary over time in Cox
      proportional hazards models (i.e., to allow the antiretroviral therapy
      coefficient to change over time). Another difficulty is that CD4 cell counts may
      underestimate the degree of immunodeficiency after prolonged zidovudine (AZT)
      monotherapy. If post-antiretroviral therapy CD4 cell counts are used to adjust
      for the stage of immunodeficiency, it may therefore be helpful to adjust for the
      duration of antiretroviral therapy with the CD4 cell count at the time of
      starting antiretroviral therapy. It is interesting to consider statistical models
      of progressive HIV-induced immunodeficiency in the context of the evolution of
      host immunity. HIV infection results in the loss of the relatively recently
      evolved adaptive CD4 T cell-mediated immunity to intracellular parasites. The
      infected host may compensate for this by making greater use of phylogenetically
      ancient, more innate protective responses. Because these compensatory responses
      are polymorphic, this results in the appearance of differences between
      individuals in the immune response to HIV as the disease progresses. Data from
      the Western Australia HIV Cohort Study support a two-stage model of
      immunopathology. The first stage of this model involves a loss of mucosal
      immunity and occurs at a variable CD4 cell count (of between 400 cells/mm3 and
      zero), and is marked by a loss of cutaneous delayed-type hypersensitivity
      responses and oral candidiasis, seborrheic dermatitis, and Pneumocystis carinii
      pneumonia. The second stage of the model involves a loss of systemic immunity and
      requires profound CD4 T-cell lymphopenia (CD4 cell count <50 cells/mm3), and is
      marked by infections such as cytomegalovirus and disseminated Mycobacterium avium
      infection. The influence of HLA type on the risk for such opportunistic
      infections becomes apparent during this late phase.

PMID- 9586649
TI  - Research potentials and pitfalls in the use of an HIV clinical database: Chelsea
      and Westminster Hospital.
AB  - This article summarizes the various problems and pitfalls in using clinical
      databases for epidemiologic research, with particular reference to an HIV
      clinical database. The combined population of HIV-infected individuals attending
      the Chelsea and Westminster Hospital, the Charing Cross Hospital, and the
      Victoria Clinic in London is the largest cohort of HIV-positive individuals in
      the U.K. A computerized database was developed in the mid-1980s and was adapted
      into a clinically oriented observational database for approximately 6,653 HIV-1
      positive registered patients from three hospital-based clinics within the
      Riverside Health Authority in London, U.K.: Chelsea and Westminster Hospital
      Clinic (n = 5,000); Charing Cross Hospital (n = 500); and the Victoria Clinic (n
      = 500). The majority (83%) of HIV-infected patients registered at these sites are
      homosexual or bisexual men. Of 2,078 patients seen within the last 6 months, 22%
      are asymptomatic and 33% have AIDS; 30% have a CD4 cell count of less than 100
      cells/mm3 and 17% have a CD4 cell count of greater than 500 cells/mm3. Dates of
      seroconversion are known for approximately 285 patients. For each patient,
      information on demographic characteristics, clinical symptoms, and HIV-related
      diagnoses, outpatient pharmacy prescriptions, day care treatments and procedures,
      and enrollment into clinical trials is routinely collected at outpatient clinic
      visits and entered into the database. Inpatient diagnoses and treatments were
      integrated into the database in September 1995. Unused serum samples from routine
      AIDS antibody or antigen testing are stored in a local specimen repository. The
      main purpose of the HIV database is to provide a multipurpose resource for use by
      physicians, researchers, and managers for administration, clinical care, and
      research. The specific functions of the database are the following: to enhance
      patient management by providing access to a clinical summary sheet detailing up
      to-date information; to serve as a research tool for clinical and epidemiologic
      research; to aid in the identification of patients eligible for planned or
      ongoing clinical trials; to provide a facility for local and regional AIDS
      surveillance and reporting; and to provide a facility for administration and
      resource management of HIV services. The major limitations of this database in
      the conduct of clinical research have been losses to follow-up and incomplete
      information about clinical outcomes, because physicians have failed to update the
      clinical information.

PMID- 9586650
TI  - The Albion Street Centre database, Sydney, Australia.
AB  - The Albion Street Centre was established in 1985 as an HIV testing and early
      management center. More than 22,000 people have been screened for HIV and other
      blood-borne infections at the Centre, and approximately 3,600 people with
      HIV/AIDS have been managed there. Approximately 1,600 patients with various
      stages of HIV disease are currently managed at the Centre by a staff of 60 health
      care professionals and about 1,000 volunteers. The Albion Street Centre's
      computer database began recording selected demographic, epidemiologic, clinical,
      and laboratory characteristics when the first patient presented in 1985. Since
      then, the complexity and utilization of the database has increased in parallel
      with improvement in the understanding of the natural history and pathogenesis of
      HIV infection. Over 100 peer-reviewed publications and presentations have been
      produced from the database and 45 clinical trials have used the database to
      identify potential subjects. All data are de-identified and are protected by
      multiple password codes. Approximately 700 variables are collected from each HIV
      positive patient at the initial visit to the Centre and up to 200 variables are
      added at each subsequent routine clinic visit. The variables collected include
      the following: standard epidemiologic characteristics; transmission and
      behavioral parameters, clinical signs and symptoms; laboratory test results;
      treatments; nutritional history; body composition parameters; psychological
      assessment results; and management history, including neuropsychological testing.
      The overall number and characteristics of patients recorded in the database are
      reported monthly, and are used to plan services, for prevention and educational
      programs, and as an indicator of the effectiveness of campaigns to encourage HIV
      positive people to attend clinics for early management. When these patients have
      been identified they are invited to participate in the study. Individual patient
      records are identified and accessed if they meet certain criteria for flagging.
      For example, patients who have lost more than 5% of their maximal weight are
      flagged and referred to the dietician for assessment. Further uses for the
      database are to identify cohorts of patients who are seroconverters and to follow
      their natural history-the Centre has over 250 patients for whom a documented HIV
      positive test has been obtained within 12 months of a documented HIV-negative
      test; to investigate clinical observations that have been associated with
      particular drug therapy, e.g., investigation of the reported association between
      the use of valacyclovir and the thrombotic thrombocytopenic purpura/hemolytic
      uremic syndrome (TTP/HUS)-like complex showed patients with terminal-stage AIDS
      demonstrated this syndrome independently of their therapy and probably as a
      consequence of multiorgan failure; and to document the relationship between
      nutritional intervention and survival, for which use of the database enabled an
      historical cohort that matched the cases under investigation to be selected. In
      conclusion, the database is a dynamic and integral part of the assessment,
      management, and research program of the Albion Street Centre, where it is used by
      all professional staff.

PMID- 9586651
TI  - Understanding the clinical and economic outcomes of HIV therapy: the Johns
      Hopkins HIV clinical practice cohort.
AB  - The Johns Hopkins AIDS Service is the principal provider of medical care for HIV
      infected patients in Maryland, a state in which the majority of HIV-infected
      patients live in an urban environment. A component of the HIV service at Johns
      Hopkins Medical Center is an information system that is used to track
      longitudinally the ambulatory and inpatient care of HIV-infected patients.
      Enrollment into this database coincides with first enrollment into the HIV
      Service. Extensive laboratory, diagnostic, clinical, and pharmaceutical
      information is collected at enrollment and is updated every 6 months. Outpatient
      and inpatient medical records, Johns Hopkins Health System automated databases,
      supplemental medical records from outside facilities, vital records, and patient
      and provider interviews are all used to obtain the detailed data that are stored
      on the database. The database also includes an economic component, which was
      added in 1994. This component links all Maryland state Medicaid claims data to
      that relating to patients who are insured by the Maryland Medical Assistance
      program, who account for approximately 60% of patients using the Johns Hopkins
      HIV Service. This data linkage facilitates detailed quantification of the costs
      of medical care for the HIV-infected patient throughout the course of the
      infection. We currently have data on about 3,000 HIV-infected patients
      representing a heterogeneous mix by race, sex, socioeconomic status, and risk
      factors for HIV transmission. Our data have been used to address a variety of
      issues regarding access to, utilization of, and clinical outcomes of HIV
      therapeutics. Clinical practice data such as ours will be increasingly important
      as the number and types of antiretroviral and other drugs for HIV infection
      continue to increase.

PMID- 9586652
TI  - Session A: Natural history of HIV disease and predictors of clinical outcome.

PMID- 9586653
TI  - Session B: The role of patient databases in assessing antiretroviral treatment.

PMID- 9586654
TI  - Session C: The role of patient databases in assessing treatment safety.

PMID- 9586655
TI  - Gastrointestinal carcinoma antigen GA733: target for immunodestruction and
      potential modifier of invasiveness and chemoresponsiveness.

PMID- 9586656
TI  - Informed consent for clinical trials: is simpler better?

PMID- 9586658
TI  - Breast Cancer Prevention Trial shows major benefit, some risk.

PMID- 9586657
TI  - Anti-estrogens come of age: a pioneer looks back.

PMID- 9586659
TI  - New initiatives for researchers rev up the Internet.

PMID- 9586660
TI  - Farmers and cancer: old crop of data gets new scrutiny.

PMID- 9586661
TI  - New cooperative trial group will focus on oncologic surgery.

PMID- 9586662
TI  - Quality of life in long-term survivors of adult-onset cancers.
AB  - The long-term survival of cancer patients has risen dramatically during the last
      few decades, yet little is known about the quality of life experienced by these
      survivors. This paper reviews research on the quality of life in long-term cancer
      survivors to identify quality-of-life concerns in this population, to provide a
      critical evaluation of the literature, and to suggest areas for future research.
      Searches of computerized literature databases were conducted to identify all
      studies of quality of life in cancer survivors that were published in English
      language journals during the period from January 1, 1980, through February 12,
      1998, and that were based on responses from individuals who have survived 5 or
      more years after the diagnosis of adult-onset cancers. Thirty-four papers were
      identified. Most studies utilized self-report questionnaires to measure quality
      of life. Although methodologies and cancer patient populations varied greatly,
      most studies showed that many survivors continue to experience negative effects
      of cancer and/or treatment on their daily lives well beyond the completion of
      therapy. Sexual functioning and/or satisfaction and psychological functioning
      were found to be concerns for many survivors. Several reports documented positive
      coping strategies and enhanced quality of life in long-term cancer survivors,
      supporting the need to measure positive aspects of quality of life as well as
      problems in this population. Study designs that more accurately measure quality
      of life among survivors of cancer by adjusting for the effects of aging and long
      term therapy and the impact of second cancers should be utilized. Additional data
      are needed to understand the needs of long-term survivors, especially of those in
      groups underrepresented in published quality-of-life studies, and to determine
      what kinds of support survivors want.

PMID- 9586663
TI  - Informed consent for clinical trials: a comparative study of standard versus
      simplified forms.
AB  - BACKGROUND: A high level of reading skill and comprehension is necessary to
      understand and complete most consent forms that are required for participation in
      clinical research studies. This study was conducted to test the hypothesis that a
      simplified consent form would be less intimidating and more easily understood by
      individuals with low-to-marginal reading skills. METHODS: During July 1996, 183
      adults (53 patients with cancer or another medical condition and 130 apparently
      healthy participants) were tested for reading ability and then asked to read
      either the standard Southwestern Oncology Group (SWOG) consent form (16th grade
      level) or a simplified form (7th grade level) developed at Louisiana State
      University Medical Center-Shreveport (LSU). Participants were interviewed to
      assess their attitudes toward and comprehension of the form read. Then they were
      given the alternate consent form and asked which one they preferred and why.
      RESULTS: Overall, participants preferred the LSU form (62%; 95% confidence
      interval [CI] = 54.8%-69.2%) over the SWOG form (38%; 95% CI = 30.8%-45.2%) (P =
      .0033). Nearly all participants thought that the LSU form was easier to read
      (97%; 95% CI = 93.1%-99.9%) than the SWOG form (75%; 95% CI = 65.1%-85.7%)
      (P<.0001). However, the degree to which the participants understood the forms was
      essentially the same for the LSU form (58%; 95% CI = 48.6%-67.0%) and the SWOG
      form (56%; 95% CI = 43.8%-66.8%). IMPLICATIONS: These findings raise serious
      questions regarding the adequacy of the design of written informed consent
      documents for the substantial proportion of Americans with low-to-marginal
      literacy skills.

PMID- 9586664
TI  - Kirsten ras mutations in patients with colorectal cancer: the multicenter
      "RASCAL" study.
AB  - BACKGROUND: Kirsten ras (Ki-ras) gene mutations occur early in the progression of
      colorectal adenoma to carcinoma. The aim of this collaborative study was to
      clarify the association between Ki-ras mutations, patient outcome, and tumor
      characteristics by use of data from colorectal cancer patients worldwide.
      METHODS: Investigators who had published data on Ki-ras and colorectal cancer
      were invited to complete a questionnaire for each patient entered into a
      database. Two-sided statistical tests were used to analyze data. RESULTS:
      Patients (n = 2721) were recruited from 22 groups in 13 countries. Mutations of
      Ki-ras codon 12 (wild type = GGT = glycine) or codon 13 (wild type = GGC =
      glycine) were detected in 37.7% of the tumors; 80.8% (584 of 723) of all the
      specified mutations occurred in codon 12, and 78.1% (565 of 723) of all the
      specified mutations were at the second base of either codon. Mutations were not
      associated with sex, age, tumor site, or Dukes' stage. Mutation rates seen in
      patients with sporadic tumors were comparable to those observed in patients with
      a predisposing cause for their cancer. Poorly differentiated tumors were less
      frequently mutated (P = .002). Multivariate analysis suggested that the presence
      of a mutation increased risk of recurrence (P<.001) and death (P = .004). In
      particular, any mutation of guanine (G) to thymine (T) but not to adenine (A) or
      to cytosine (C) increased the risk of recurrence (P = .006) and death (P<.001).
      When individual, specific mutations were evaluated, only valine codon 12 was
      found to convey an independent, increased risk of recurrence (P = .007) and death
      (P = .004). CONCLUSIONS: Ki-ras mutations are associated with increased risk of
      relapse and death, but some mutations are more aggressive than others.

PMID- 9586665
TI  - Telomerase activity in lung cancer cells obtained from bronchial washings.
AB  - BACKGROUND: Telomerase, a ribonucleoprotein enzyme that functions in the
      maintenance of telomeres (specialized structures at the ends of chromosomes), has
      been reported to be a novel diagnostic marker for malignant diseases. We sought
      to determine whether measurement of telomerase activity in bronchial washings is
      of value in the diagnosis of lung cancer. METHODS: Extracts of cells in bronchial
      washings were analyzed for telomerase activity by use of a telomeric repeat
      amplification protocol (TRAP) assay. Telomerase activity inside cells was
      evaluated by use of an in situ TRAP assay. The results of both TRAP assays were
      compared with those obtained from cytologic examination, which employed standard
      Papanicolaou staining. RESULTS: When results from the two TRAP assays were
      combined, telomerase activity was detected in bronchial washings from 18 (82%;
      95% confidence interval [CI] = 60%-95%) of 22 patients with lung cancer. In
      contrast, cancer cells were detected by cytologic examination in the bronchial
      washings of nine (41%; 95% CI = 21%-64%) of the same 22 patients, a statistically
      significant difference (two-sided P = .0061). In patients with lung cancer,
      telomerase-positive cells could be detected in bronchial washings irrespective of
      tumor location--11 of 14 (79%; 95% CI = 49%-95%) peripheral cancerous lesions and
      seven of eight (88%; 95% CI = 47%-100%) central cancerous lesions were detected
      by use of TRAP assays (for comparison, two-sided P = .5349). CONCLUSIONS: A high
      percentage of patients with lung cancers had detectable telomerase activity in
      bronchial washings. Thus, the use of a cell extract-based or an in situ TRAP
      assay in addition to cytologic examination may make the diagnosis of lung cancer
      more reliable.

PMID- 9586666
TI  - Colorectal carcinoma invasion inhibition by CO17-1A/GA733 antigen and its murine
      homologue.
AB  - BACKGROUND: The gastrointestinal carcinoma antigen GA733 is a potential target
      for passive and active immunotherapy for patients with colorectal carcinoma. This
      antigen has been characterized previously as a homophilic adhesion (i.e.,
      adhesion to self) protein, but the functional consequences of homophilic adhesion
      for tumor growth and invasion are unknown. The availability of a murine homologue
      of GA733, i.e., murine epithelial glycoprotein (mEGP), allows for functional
      analysis of cell adhesion as it relates to tumor growth and invasion, both in
      vitro and in vivo. METHODS: CT-26 murine colorectal carcinoma cells were
      transfected with complementary DNAs encoding either the human or the murine
      antigen. GA733- or mEGP-producing cells were evaluated for homophilic adhesion,
      growth on plastic surfaces, colony formation in soft agar, and invasion through a
      reconstructed basement membrane (Matrigel). mEGP-producing cells were also
      examined for their capacity to metastasize in mice. Reported P values are two
      sided. RESULTS: Compared with control cells, mEGP-producing cells showed
      significantly lower growth rates, colony formation, and invasion through Matrigel
      in vitro (all P values <.05). Compared with vector-only transfected cells and
      parental cells, mEGP-producing cells showed a reduction in metastatic potential
      in syngeneic immunodeficient and immunocompetent mice (all P values <.05). In
      contrast to mEGP-transfected cells, GA733-transfected cells did not exhibit
      significantly reduced growth or colony formation in vitro (all P values >.05).
      However, GA733-transfected cells did show reduced invasion through Matrigel
      compared with vector-only transfected cells or parental cells (all P values
      <.05). CONCLUSION: The adhesion proteins GA733 and mEGP inhibit invasion of tumor
      cells.

PMID- 9586667
TI  - Analysis of loss of heterozygosity in 399 premalignant breast lesions at 15
      genetic loci.
AB  - BACKGROUND: Usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH),
      and ductal carcinoma in situ (DCIS) are risk factors for invasive breast cancer
      (IBC), suggesting that these lesions may be direct precursors of IBC. To identify
      genetic changes that may be important in the early development of precursor
      lesions and their progression to malignant or invasive disease, we examined 399
      putative precursors (211 UDH, 51 ADH, 81 non-comedo DCIS, and 56 comedo DCIS) for
      loss of heterozygosity (LOH) at 15 polymorphic genetic loci known to exhibit high
      rates of loss in IBC. We also assessed the sharing of LOH by putative precursors
      and synchronous cancers. METHODS: The polymerase chain reaction was used to
      analyze DNA from microdissected archival specimens. RESULTS AND CONCLUSIONS: In
      hyperplasias from noncancerous breasts (i.e., without DCIS and/or IBC in analyses
      of hyperplasias), LOH at any given locus was rare (range, 0%-15%), although 37%
      of UDH and 42% of ADH lesions showed loss for at least one locus, suggesting that
      the development of hyperplasias can involve many different tumor suppressor
      genes. In DCIS from noncancerous breasts (i.e., without IBC in analyses of DCIS),
      LOH was common, with 70% of noncomedo lesions and 79% of comedo lesions showing
      at least one loss. In DCIS, substantial rates of loss (up to 37%) were observed
      at loci on chromosomes 16q, 17p, and 17q, suggesting that inactivated tumor
      suppressor genes in these regions may be important in the development of
      noninvasive breast cancer. When DCIS lesions from cancerous and noncancerous
      breasts were compared, substantially more LOH was observed in the cancerous
      breasts at a few loci (on chromosomes 2p, 11p, and 17q), suggesting that genetic
      alterations in these regions may be important in the progression to invasive
      disease. Among specimens harvested from cancerous breasts, 37% of UDH, 45% of
      ADH, 77% of noncomedo DCIS, and 80% of comedo DCIS lesions shared LOH with
      synchronous cancers at one locus or more, supporting the idea that the putative
      precursors and the cancers are genetically related.

PMID- 9586668
TI  - Oral clodronate and reduction in loss of bone mineral density in women with
      operable primary breast cancer.
AB  - BACKGROUND: Women with primary breast cancer who receive systemic therapy may
      experience ovarian failure or early menopause, leading to a loss of bone mineral
      density (BMD). Loss of BMD may be reduced by use of bisphosphonates, compounds
      that inhibit the action of osteoclasts (cells that absorb or remove bone tissue).
      We have conducted a double-blind, randomized, two-center trial to evaluate BMD in
      women with primary breast cancer who were given the bisphosphonate clodronate
      (1600 mg/day orally) or placebo for 2 years. METHODS: From August 31, 1990,
      through March 31, 1996, more than 300 eligible patients had been accrued,
      randomly assigned to study treatment, given the appropriate primary surgical care
      and systemic (chemotherapy and/or tamoxifen) therapy, and had completed follow-up
      for at least 1 year. BMD in the lumbar spine and in the hip, including the
      trochanteric area, was measured by use of dual-energy x-ray absorptiometry at the
      beginning of treatment and after 1 and 2 years of treatment. Changes in BMD were
      calculated as percent changes from the initial readings. Treatment effects for
      clodronate versus placebo (i.e., mean percent changes in BMD with clodronate
      minus mean percent changes in BMD with placebo) at 1 and 2 years for individual
      sites were calculated. RESULTS: After 1 year, the treatment effects for
      clodronate versus placebo in the lumbar spine, the total hip, and the trochanter,
      respectively, were as follows: +2.38% (95% confidence interval [CI] = 1.36-3.41),
      +0.74% (95% CI = -0.13 - 1.60), and +1.29% (95% CI = 0.24-2.34). After 2 years,
      the corresponding treatment effects were +1.72% (95% CI = 0.12-3.34), +1.85% (95%
      CI = 0.51-3.20), and +2.30% (95% CI = 0.66-3.94), respectively. CONCLUSIONS: Oral
      clodronate appears to reduce the loss of BMD in patients who receive treatment
      for primary breast cancer.

PMID- 9586670
TI  - Prognostic importance of low c-erbB2 expression in breast tumors.

PMID- 9586669
TI  - Sun-related risk factors in melanoma-prone families with CDKN2A mutations.

PMID- 9586671
TI  - The female prostate.

PMID- 9586672
TI  - Assistive devices: integral to the daily lives of human beings.

PMID- 9586673
TI  - Questionnaire to evaluate the effects of assistive devices and altered working
      methods in women with rheumatoid arthritis.
AB  - The objectives of the study were to identify perceived difficulty and reduction
      of difficulty when using assistive devices and altered working methods in
      performing daily activities and to detect which activities were unaffected by
      interventions. Twenty-one women aged 29-65 years with rheumatoid arthritis
      answered the Evaluation of Daily Activity Questionnaire (EDAQ), which contains
      102 items divided into 11 dimensions of daily activities. The women rated their
      perceived difficulty twice: first when not using devices or altered methods and
      then when using them. The use of devices or altered methods led to a reduction in
      perceived difficulty in 42% of the ratings. The number of items that the women
      found difficult when not using devices/altered methods ranged between 13 and 99.
      With the interventions, the number of items still found difficult decreased to
      between 6 and 57, 91% of the devices provided were still in use. The dimensions
      Eating, Cooking and Toileting contained the most items affected by the use of
      devices such as lever taps, springy scissors, breadknife and wrist orthosis. Few
      effective devices were identified for the dimensions Dressing, Washing, Cleaning
      and Mobility Outdoors. It was concluded that the EDAQ represents a new approach
      to demonstrating difficulties in performing various daily activities, to
      describing the effects of assistive devices/altered methods, and to identifying
      areas not affected by interventions.

PMID- 9586674
TI  - The early clinical history of salicylates in rheumatology and pain.
AB  - The first clinical reports on the treatment of fever and pain with salicylate
      containing natural willow bark remedies were made by the English clergyman Edward
      Stone in 1763. The pharmacologically active principles were isolated from natural
      sources by Italian, German and French scientists between 1826 and 1829. Salicylic
      acid was first synthesised by the German Gerland in 1852 and a year later the
      Frenchman Gerhardt synthesised acetylsalicylic acid. The first reports on the
      clinical use of salicylic acid in rheumatic disorders were made independently by
      the two German physicians Stricher and Reiss in 1876. Acetylsalicylic acid was
      rediscovered by Hoffmann in 1897 and by the turn of the century it had gained
      worldwide recognition in the treatment of pain and rheumatological disorders.
      Reports on adverse events relating to gastrointestinal intolerance and bleeding
      appeared early, but were largely neglected until the 1950s. Today, salicylates
      are still widely used as analgesic, antipyretic and anti-inflammatory drugs. New
      indications, such as thrombosis prophylaxis, have emerged during the last
      decades, and yet others are being explored.

PMID- 9586675
TI  - Relations between surface expression of the interleukin-2 receptor and release of
      the soluble form of the receptor in cultured mononuclear cells from patients with
      rheumatoid arthritis or systemic lupus erythematosus.
AB  - The relationship between surface expression of the interleukin-2 receptor (IL-2R)
      and release of the soluble form of the receptor (sIL-2Ralpha or sCD25) was
      investigated with peripheral blood mononuclear cells (PBMCs) from individuals
      with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). The
      spontaneous release of sCD25 was significantly increased in PBMCs from RA
      patients and decreased in cells from SLE patients, compared with normal controls.
      However, the extent of sCD25 release from phytohaemagglutinin (PHA)-stimulated
      PBMCs did not differ between RA or SLE patients and normal controls. The serum
      concentration of sCD25 was significantly increased in SLE or RA patients compared
      with the normal controls. Whereas the surface expression of CD25 by unstimulated
      PBMCs did not differ among the three groups of subjects, this parameter was
      significantly reduced for PHA-stimulated PBMCs from RA patients relative to those
      from normal controls. The surface expression of CD25 showed a positive
      correlation with sCD25 release for PBMCs from SLE patients under either basal or
      stimulated conditions. No such relation was apparent for cells from RA patients.
      The surface expression of IL-2Rbeta (CD 122) under basal or stimulated conditions
      was significantly reduced in PBMCs from RA or SLE patients, compared with cells
      from normal controls. Thus, the increased concentration of sCD25 in the serum of
      individuals with these autoimmune rheumatic diseases may result from two
      different mechanisms: an increase in the spontaneous release of sCD25 in RA, and
      reduced clearance of this protein in SLE.

PMID- 9586676
TI  - Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases,
      cytokines and prostaglandin E2 production by human articular chondrocytes.
AB  - The in-vitro effects of avocado and soybean unsaponifiable residues on neutral
      metalloproteinase activity, cytokines and prostaglandin E2 (PGE2) production by
      human articular chondrocytes were investigated. Avocado and soybean
      unsaponifiable residues were mixed in three ratios: 1:2 (A1S2), 2:1 (A2S1) or 1:1
      (A2S2). Freshly isolated human chondrocytes were cultured for 72 h in the absence
      or presence of interleukin-1beta, (IL-1beta) (17 ng/ml), with or without
      unsaponifiable residue mixtures at a concentration of 10 microg/ml. A/S
      unsaponifiable residues were also tested separately at concentrations of 3.3, 6.6
      and 10 microg/ml. All A/S unsaponifiable mixtures reduced the spontaneous
      production of stromelysin, interleukin-6 (IL-6), interleukin-8 (IL-8) and
      prostaglandin E2 (PGE2) by chrondrocytes. At concentrations of 3.3 and 6.6
      microg/ml, A/S residues, tested separately, were potent inhibitors of the
      production of IL-8 and PGE2. Nevertheless, only avocado residue inhibited IL-6
      production at these concentrations. A/S unsaponifiable mixtures had a more
      pronounced inhibitory effect on cytokine production than avocado or soybean
      residues added alone. As anticipated, IL-1beta induced a marked release of
      collagenase, stromelysin, IL-6, IL-8 and PGE2. A/S unsaponifiable mixtures
      partially reversed the IL-1 effects on chrondrocytes. These findings suggest a
      potential role for A/S unsaponifiable extracts in mitigating the deleterious
      effects of IL-1beta: on cartilage.

PMID- 9586677
TI  - Bone status assessed by quantitative ultrasound in healthy postmenopausal Polish
      women: normative data.
AB  - In this study, ultrasound measurements of the calcaneus of 712 healthy
      postmenopausal Polish women aged 50-85 years (mean age 59.5 years) were
      performed. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were
      obtained with a Lunar Achilles machine. The women in the study were volunteers
      evaluated at the Osteoporotic Centre for screening purposes. The results showed a
      decrease in ultrasound values within the age range 52-74 years for BUA (9.8%) and
      SOS (1.9%). Simple linear regression analysis showed a negative, significant
      correlation with age for BUA (r=-0.36) and SOS (r=-0.38). Years since menopause
      (YSM) showed significant correlations with BUA and SOS (r=-0.33 and -0.35,
      respectively). Using multiple regression analysis, the following equations were
      obtained: BUA=66.04 - 0.31Age + 0.06Weight - 0.18 YSM + 0.27Height + 0.52 Body
      mass index and SOS=1547.17 - 1.02Age + 0.38Weight - 0.48 YSM. Several weak, but
      significant, correlations between ultrasound values and weight, height and body
      mass were noted (r ranged from 0.09 to -0.29). A decrease of ultrasound values
      was expressed mainly in the first 6-10 years of the postmenopause period. The
      pattern of this decrease was similar to data published by other authors, but
      values in postmenopausal Polish women are slightly lower.

PMID- 9586678
TI  - The relationship between osteoarthritis and osteoporosis in the spine.
AB  - The degree of osteoarthritis and osteoporosis in the lumbar spine has been
      compared in patients with spinal osteoarthritis and osteoporotic fractures and in
      a normal control group of 252 elderly subjects, to investigate the relationship
      between osteoarthritis and osteoporosis in the spine. The two indices were highly
      significantly different in the three groups (p<0.01). The degree of
      osteoarthritis in the osteoarthritic patients was higher (p<0.01) than in the
      fracture patients and the normal control subjects, while the degree of
      osteoporosis in the fracture patients was higher than in osteoarthritic patients
      and normal controls (p<0.01). These data support the conclusion that
      osteoarthritis and osteoporosis in the spine are inversely related.

PMID- 9586679
TI  - Stress fractures.
AB  - Stress fractures are being increasingly reported as a common cause of morbidity
      in both healthy populations and those with underlying diseases involving abnormal
      bone. An insight into the types and pathogenesis of stress fractures is necessary
      to considering the diagnosis, management and prevention of such conditions. The
      classification, aetiology and aspects of management are discussed.

PMID- 9586680
TI  - Methotrexate therapy in systemic-onset juvenile rheumatoid arthritis in Saudi
      Arabia: a retrospective analysis.
AB  - Eighteen patients (nine girls, nine boys) with systemic onset juvenile rheumatoid
      arthritis (SO-JRA) treated with methotrexate (MTX) for a mean period of 18 months
      (range 6-41 months) were analysed to evaluate the safety and efficacy of MTX in
      this disease subtype. The MTX dose ranged from 2.5 to 15 mg/week with a mean
      cumulative dose of 684.9 mg/patient at the last follow-up visit. Systemic
      features were severe in 10 patients before MTX was started. None of these
      patients showed systemic features at the last follow-up visit. Sixteen patients
      (89%) showed improvement in both the active joint count (from a mean of 12.0 to
      1.3 joints/patient) and function class (from a mean of 3.0 to 1.3) while
      receiving MTX. Eleven patients (61%) showed a significant decrease in the
      erythrocyte sedimentation rate (>50% of the initial value), an improvement in
      anaemia (haemoglobin >2 g) and reduced thrombocytosis (platelets 2 x 10[5]). Of
      the patients receiving corticosteroids, three patients (20%) were able to
      discontinue prednisone and the dose was reduced to less than 50% of the initial
      dose in seven patients (47%). At these doses of MTX, no gastrointestinal, hepatic
      or haematological toxicity was encountered and none of the patients withdrew
      because of toxicity or lack of efficacy. This report suggests that MTX is an
      effective and safe treatment in controlling systemic and articular features in
      this subtype of JRA.

PMID- 9586682
TI  - Computed tomographic imaging of subcutaneous gouty tophi.

PMID- 9586683
TI  - Focal myositis.

PMID- 9586681
TI  - Giant cell arteritis with ocular complications discovered simultaneously in two
      sisters.

PMID- 9586684
TI  - Neurobehavioural and psychiatric manifestations in a case of ANA-negative SLE
      with antiphospholipid antibodies.

PMID- 9586685
TI  - A new case of Streptococcus equisimilis septic arthritis.

PMID- 9586686
TI  - Therapeutic effect of tiopronin following D-penicillamine toxicity in a patient
      with rheumatoid arthritis.

PMID- 9586688
TI  - Tuberculosis of the fascia lata.

PMID- 9586687
TI  - Cerebral blood flow abnormalities detected by SPECT in Behcet's-syndrome-related
      psychiatric disorders.

PMID- 9586690
TI  - Adult Still's-disease-like illness in a patient with silicone breast implants.

PMID- 9586689
TI  - Collagenous colitis associated with rheumatoid arthritis and anticardiolipin
      antibodies.

PMID- 9586691
TI  - Soluble interleukin-2 receptor and interleukin-6 levels: evaluation during
      cyclosporin A and methotrexate treatment in psoriatic arthritis.

PMID- 9586692
TI  - Differences of HIV envelope protein between HIV-1 and HIV-2: possible relation to
      the lower virulence of HIV-2.

PMID- 9586693
TI  - Autoimmune T-cell response to the CD4 molecule in HIV-infected patients.
AB  - In a previous study, we demonstrated that by downregulating plasma membrane CD4
      and increasing its processing, human immunodeficiency (HIV)-1-gp120 unveils
      hidden CD4 epitopes, inducing an in vitro anti-CD4-specific T-cell response. We
      report herein that this mechanism may potentially have important implications in
      HIV immunopathogenesis, because it could take part in the severe depletion of
      CD4+ cells that characterizes acquired immune deficiency syndrome (AIDS) and be
      related to disease progression. Freshly isolated peripheral blood lymphocytes
      (PBMC) from about 1/4 of a conspicuous cohort of HIV-infected patients responded
      to CD4 and this response was correlated with beta2-microglobulin levels, widely
      recognized as marker for progression of HIV infection. Moreover, we provide
      evidence that a CD4-specific T cell priming can occur in vivo, following a gp120
      or anti-CD4 monoclonal antibody (mAb)-mediated CD4 molecule downregulation on
      antigen-presenting cells (APC). To our knowledge, this is the first study
      indicating that an autoimmune T-cell response is linked to HIV infection and that
      it could have an important impact on the immunopathogenesis of this disease.

PMID- 9586694
TI  - Activation of lymphocytes by HHV-6 antigen in normal children and adults.
AB  - We investigated the immune reaction of lymphocytes in response to human herpes
      virus-6 (HHV-6) in normal children and adults. Cell proliferation was assayed by
      measurement of the incorporation of 5-bromo-2'-deoxyuridine (BrdU) by enzyme
      linked immunosorbent assay (ELISA), and changes in expression of interleukin-2
      receptors (IL-2Rs) (alpha-, beta3-, and gamma-chain) were assayed by flow
      cytometry. Incorporation of BrdU and expression of IL-2Rs (alpha-, beta-, and
      gamma-chain) in CD4+, CD8+, and CD45RO+ lymphocytes were increased when
      peripheral blood mononuclear cells (PBMC) from HHV-6 seropositive children aged 3
      to 12 years and adults were cultured with HHV-6 antigen compared with control
      antigen. In contrast, cord blood mononuclear cells (CBMC) and PBMC from
      seronegative children did not show cell proliferation and changes in expression
      of IL-2Rs. In seropositive children less than 2 years of age, the magnitude of
      cell proliferation was low and IL-2Rs (alpha-, beta-, and gamma-chain) in CD8+
      cells and IL-2Rs (alpha-chain) in CD45RO+ cells were increased. These data
      suggest that children below the age of 2 had immature lymphocytic response to HHV
      6 antigen. Deletion of monocytes from PBMC and the addition of a mixture of anti
      IL-2Rs (alpha-, beta-, and gamma-chain) antibodies reduced cell proliferation in
      response to HHV-6, suggesting the requirement of the presence of monocytes and
      expression of IL-2Rs.

PMID- 9586695
TI  - A vector DNA vaccine encoding pseudorabies virus immediate early protein
      demonstrates partial protection in mice against lethal virus challenge.
AB  - An earlier study in our laboratory provided evidence that pseudorabies virus
      (PrV) immediate early protein (IE180) may contribute to the overall immune
      response against PrV. To examine the response by IE180 more closely, we initiated
      a vaccine trial in mice with a vector DNA construct that contains the gene
      encoding for IE180, designated pcDNAIE180. The DNA vaccine was delivered in gold
      microcarriers using a Helios Gene Gun, and 70% of BALB/c mice given the DNA
      vaccine (2 microg/mouse) seroconverted within 2 weeks. The remaining negative
      mice seroconverted after a single vaccine booster. Essentially similar results
      were obtained on vaccination of C57BL/6 mice, whereas C3H/HeJ mice remained
      negative after the first vaccination, but responded after a booster. Seven months
      after immunization with pcDNAIE180, an overall 25% of BALB/c, C3H/HeJ, and
      C57BL/6 mice receiving a lethal PrV challenge were protected. In addition, a
      significant passive transfer of IE180-specific antibodies to the offspring from
      pregnant mice vaccinated with pcDNAIE180 was observed. Interestingly, a moderate
      level of protection (27.6%) was also observed when these offspring received a
      lethal PrV challenge. Moreover, an enhancement of immune responses and a twofold
      increase in the level of protection were observed in mice that received a second
      vaccine booster by gene gun 8 months after the first vaccination. Together, these
      data support the theory that IE180 may indeed play a role in the overall
      protective immunity against PrV.

PMID- 9586696
TI  - Development of a syngeneic bovine fibroblast cell line: implications for the
      study of bovine cytotoxic T lymphocytes.
AB  - The study of T-cell-mediated cytotoxicity in domestic animals, especially in
      cattle, has been hampered by the lack of proper restimulatory as well as target
      systems. While the currently available bovine cell lines have not been typed for
      the major histocompatibility complex (MHC) class I molecules they express,
      methods to derive lines of cells obtained from animals that are MHC-typed have
      not been thoroughly explored. In the present study, we describe a method for the
      development of cell lines from MHC-typed animals. Cells obtained from the skin of
      a calf typed as bovine lymphocyte antigen-A11/-A13 were transfected with a
      plasmid containing the whole genome of simian vacuolating virus 40 (SV40). A cell
      line was derived from the resultant transfectants. This cell line expressed
      bovine MHC class I molecules on the cell surface, and SV40 large T antigen in the
      nucleus. The cells were permissive to the replicative cycle of bovine herpesvirus
      1 (BHV-1), and the major glycoproteins of BHV-1 were expressed at expected times
      after infection. The present study should contribute to the study of cytotoxic T
      lymphocyte response of cattle to BHV-1 and other intracellular pathogens.

PMID- 9586697
TI  - A tetrazolium-based colorimetric assay for titration of neutralizing antibodies
      against vaccinia virus.
AB  - A colorimetric assay for titration of neutralizing antibodies against vaccinia
      virus was developed. The test is based on the ability of live cells in culture to
      reduce the yellow tetrazolium salt MTT (thiazolyl-blue), to its blue formazan
      derivative. Antisera from individuals vaccinated with vaccinia virus against
      smallpox were serially diluted, incubated with 100 plaque-forming units (PFU) of
      vaccinia virus for 1 hour at 37 degrees C, and then transferred to a 96-well
      plate containing monolayers of B-SC-1 cells. After incubation for 3 to 4 days at
      37 degrees C, when more than 80% of the control infected cultures exhibited high
      degree of cytopathogenic effect, MTT was added. The absorbance of the formazan
      formed and extracted by dimethylsulfoxide was read at 492 nm by an automatic
      microplate spectrophotometer. A good correlation was found between the results
      obtained using this newly developed method and those of the plaque-reduction
      assay.

PMID- 9586698
TI  - Color Doppler hemodynamic evaluation of flow to normal hip.
AB  - This study was aimed to quantitate hemodynamic flow to the normal proximal femur
      and to evaluate the effect of internal rotation on blood flow measurements in the
      hip to assess the capability of Doppler ultrasonography to detect a simulated
      ischemic situation. Forty hips in 20 adult healthy volunteers age 22 to 62 years
      (mean age, 39.5 years) were examined in the supine position in neutral position
      and during internal rotation (simulated ischemia). Medial and lateral circumflex
      arteries and veins were examined using standard ultrasound equipment with color
      and power Doppler capabilities. Arterial pulsatility index and maximal arterial
      and venous velocities were determined. Pulsatility index values in the medial
      circumflex artery were significantly (P < 0.05) changed during internal rotation
      of the leg. A drop in pulsatility index of more than 1.4 on the right and 2.2 on
      the left hip with respect to the normal neutral position was considered abnormal.
      The peak systolic velocity did not change significantly. The venous return showed
      a consistent increase in flow velocity during internal rotation, but this was
      borderline in terms of significance. Participants older than 40 years showed more
      prominent changes in pulsatility index during internal rotation. Repeat
      measurements performed in 10 hips showed only a 5% mean change in the pulsatility
      index values from the previous series of measurements. Changes in pulsatility
      index values occurred when flow in the proximal femur was compromised (internal
      rotation). These changes were particularly significant in the medial circumflex
      artery, which is the primary vascular supply of the femoral head and neck.
      Changes also were observed in the circumflex veins (velocity increased) on
      internal rotation; however, they were not statistically significant. Doppler
      ultrasonography of the medial circumflex artery is a potential tool for the
      assessment and follow-up of hip vascularity.

PMID- 9586699
TI  - Diffuse prostatic lesions: role of color Doppler and power Doppler
      ultrasonography.
AB  - The purpose of this study was to assess the role of color Doppler ultrasonography
      and power Doppler ultrasonography in the identification of diffuse prostatic
      lesions. Forty male patients underwent gray scale transrectal ultrasonography,
      color and power Doppler sonography, and transrectal ultrasonographically guided
      biopsy. Transrectal ultrasonographically guided biopsy revealed cancer in 23
      patients and benign lesions in 17 patients. Among the prostatic cancers 82.6% (19
      of 23) showed increased flow signals, whereas 23.5% (four of 17) of benign
      lesions showed increased flow signals on color or power Doppler ultrasonography.
      If we consider increased flow signal on color or power Doppler sonography as a
      sign of a prostate cancer in diffuse prostatic lesions, these modalities have a
      sensitivity of 82.6%, specificity of 76.5%, and positive predictive value of
      82.6%. On the basis of our study, we may conclude that color and power Doppler
      ultrasonography are useful in the identification of diffuse prostatic lesions.

PMID- 9586700
TI  - Verifying complete obliteration of carotid artery-cavernous sinus fistula: role
      of color Doppler ultrasonography.
AB  - The purpose of this study was to evaluate the role of color Doppler
      ultrasonography in verifying obliteration of carotid artery-cavernous sinus
      fistula before and after therapeutic embolization or gamma knife radiosurgery.
      Before treatment, carotid artery-cavernous sinus fistula showed the following
      data on color Doppler ultrasonography: (1) increased blood flow in the common
      carotid artery (220 to 1264 ml/min with mean+/-SD of 728+/-378 ml/min); internal
      carotid artery (435 to 1097 ml/min with mean+/-SD of 834+/-216 ml/min) in
      fistulas of the direct type; and external carotid artery (85 to 257 ml/min with
      mean+/-SD of 170+/-75 ml/min) in fistulas of the indirect type in comparison to
      the contralateral side; (2) reverse pulsatile flow or spiculated wave form with
      turbulent flow in the engorged superior ophthalmic vein on the lesion side in all
      patients. All of the above abnormal hemodynamic changes became normal in six
      patients immediately after first embolization, in two patients with balloon
      embolization combined with subsequent direct embolization by direct puncture
      through the superior orbital fissure or internal carotid artery embolization, and
      in five patients after gamma knife radiosurgery at 4, 4, 8, 9, and 9 months,
      respectively. Color Doppler ultrasonography might be a good modality in long-term
      follow-up of carotid artery-cavernous sinus fistula after gamma knife
      radiosurgery and embolization.

PMID- 9586701
TI  - Doppler echocardiographic findings in patients with right ventricular infarction.
AB  - Doppler Echocardiographic Findings in Patients with Right Ventricular Infarction
      Transthoracic Doppler echocardiography was performed in 96 consecutive patients
      with right ventricular infarction treated with thrombolysis. The bedside
      examination was performed before and 2 to 3 hours after thrombolytic therapy, and
      a subsequent follow-up examination was scheduled for 7 days later. The in
      hospital and long-term course was determined for all patients. Significant
      differences were found in echocardiographic findings after the thrombolytic
      therapy: the right ventricular diameter decreased from 28.8 mm+/-5.8 to 22.5 mm
      +/- 4.3 (P < 0.001), tricuspid regurgitant flow peak velocity was reduced from
      2.9 m/s +/- 0.3 to 2.0 m/s +/- 0.5 (P < 0.001). The analysis of interatrial
      septal motion and interventricular septal motion showed a normalization in many
      patients. Major complications and deaths were more frequent in patients with
      echocardiographic findings of pulmonary hypertension persisting after
      thrombolytic therapy. Echocardiographic findings involving the right side of the
      heart are frequent in patients with right ventricular infarction. The presence of
      a severe tricuspid regurgitation and of an abnormal septal motion in patients
      with acute myocardial infarction indicates involvement of the right ventricle.

PMID- 9586702
TI  - Sonographic appearance of mammary oil cysts.

PMID- 9586703
TI  - Gallbladder cancer: can ultrasonography evaluate extent of disease?
AB  - This study reviews the spectrum of sonographic findings in patients with
      gallbladder cancer, attempts to determine if sonography can identify patients
      with potentially resectable disease, and emphasizes the limitations of
      ultrasonography in the evaluation of -gallbladder cancer. Thirty-five consecutive
      patients with histologically proven gallbladder carcinoma who had preoperative
      abdominal ultrasonography and surgery were identified. Involvement of the
      gallbladder and gallbladder fossa, metastases, bile ducts, portal vein, and
      adjacent lymph nodes was assessed sonographically. The extent of disease and
      staging as revealed by sonography was compared to operative and surgical
      pathologic findings. Masses in the gallbladder or gallbladder fossa were present
      at surgery in 26 patients; 22 (85%) of these masses were shown by sonography.
      Sonography identified six (67%) of nine cases of pathologically confirmed liver
      metastases, 11 (79%) of 14 cases of bile duct involvement, and two (67%) of three
      cases of portal venous involvement by tumor. Sonography revealed lymph node
      metastases in only five (36%) of 14 patients. None of the 12 cases with
      peritoneal metastases was identified sonographically. By surgical staging 16
      (46%) patients had potentially resectable disease (stage III or less), and 19
      (54%) patients had unresectable stage IV disease. Sonography correctly identified
      15 (94%) of 16 patients with potentially resectable disease and seven (37%) of 19
      patients with advanced disease. Twelve patients with advanced disease were under
      staged: nine had peritoneal metastases, two had liver metastases, and one had
      celiac adenopathy, which was not shown by sonography. In conclusion, sonography
      is reliable in the detection of a primary gallbladder mass or of local extension
      of tumor into the liver. However, sonographic findings do not accurately reflect
      the full extent of disease, and sonography is particularly limited in the
      diagnoses of metastases to the peritoneum and lymph nodes.

PMID- 9586704
TI  - Transrectal sonographic investigation of urethral and paraurethral structures in
      women with stress urinary incontinence.
AB  - Transrectal sonography of the urethra was used in 14 asymptomatic volunteers, 37
      women with frequency-urgency syndrome, 42 patients with mild stress urinary
      incontinence, and 18 with severe stress urinary incontinence. Transverse scanning
      over the midurethra was performed and cross-sectional images of the urethral and
      paraurethral structures were compared among the four groups, with P < 0.05 being
      considered statistically significant. The total cross-sectional area of the
      midurethra was significantly smaller in patients with stress urinary incontinence
      than in those without this disorder (86.7+/-29.9 versus 104+/-35.6 mm2, P =
      0.005); this difference resulted from a significantly smaller peripheral striated
      muscle component in patients with stress urinary incontinence (42.8+/-20.7 versus
      58.3+/-27.3 mm2, P = 0.001). The thickness of the urethropelvic ligaments was
      significantly thinner in patients with stress urinary incontinence than in those
      without (5.9+/-1.7 versus 8.9+/-2.1 mm, P < 0.001). The distribution of the
      peripheral striated muscle around the urethra was variable: complete surrounding
      the urethra was noted in 35.7% of the control women and in 48.6% of frequency
      urgency patients, but only in 16.7% of patients with mild stress urinary
      incontinence and 5.3% of patients with severe disease. Bladder neck incompetence
      was seen in 42 patients with stress urinary incontinence but in none of the
      control women. The length of the pubourethral ligaments was similar in the four
      groups. Our finding showed that stress urinary patients had a smaller striated
      muscle component in the midurethra and thinner urethropelvic ligaments. These
      defects in the continence mechanisms might have great implications in the
      pathophysiology of stress urinary incontinence. Transrectal sonography of the
      urethra is a valuable investigative tool in assessing urethral and paraurethral
      conditions in patients with stress urinary incontinence before deciding treatment
      modality.

PMID- 9586705
TI  - Comparison of sonograms and liver histologic findings in patients with chronic
      hepatitis C virus infection.
AB  - Gray scale ultrasonographic images of the liver were correlated with histologic
      findings in patients with chronic hepatitis C virus infection. The gray scale
      patterns of 64 livers with chronic hepatitis C virus infection were categorized
      as normal, fatty, fibrofatty, fibrotic, or inflammatory and were graded as mild,
      moderate, or severe. Liver biopsy specimens also were analyzed for the presence
      of fat, inflammation, and fibrosis and graded similarly. No correlation was found
      between fatty and fibrofatty sonographic findings with any of the three
      histologic patterns. Correlations were found between fibrotic sonographic
      findings and both fibrotic and inflammatory histologic findings (r = 0.27; P =
      0.03). Although some pathologic features of liver disease were detected by
      ultrasonography, no useful correlation was noted between results of sonography
      and histologic examination.

PMID- 9586707
TI  - Transperineal ultrasonographic diagnosis of vesicovaginal fistula.

PMID- 9586706
TI  - Ultrasonographic diagnosis of trisomy 18: is it practical in the early second
      trimester?
AB  - The objective of this paper was to determine the rate of prenatal detection of
      ultrasonographic abnormalities in fetuses with trisomy 18 during the early second
      trimester. Our prenatal diagnosis database (encompassing January 1987 to June
      1996) was searched for all patients referred for prenatal genetic evaluation
      between 14 and 22 weeks of gestation and who were found to have a fetus with a
      trisomy 18 karyotype. The sonographic reports and films were evaluated for the
      presence or absence of fetal anatomic abnormalities. Thirty-five fetuses were
      identified with a mean age of 17.3+/-2.0 (standard deviation) weeks. Thirty of
      the 35 (86%) had at least one detected abnormality. Most fetuses had more than
      one abnormality, with the mean number of abnormalities per fetus being three
      (range, 0 to 6). The most common abnormalities noted were persistent abnormal
      position of fetal fingers (89%); choroid plexus cysts (43%); abnormally shaped
      fetal head (strawberry or lemon) (43%); two-vessel umbilical cord (40%); cardiac
      defects (37%); intrauterine growth restriction (29%); omphalocele (20%); neural
      tube defects (9%); and cystic hygroma or lymphangiectasia (14%). Abnormalities of
      amniotic fluid volume (12%) and renal defects (9%) were seen less frequently.
      These data suggest that in the early second trimester, the time of most routine
      screening ultrasonographic examinations, most but not all fetuses with trisomy 18
      have sonographically detectable anatomic abnormalities. The fetal hand appears to
      be abnormal in most early second trimester fetuses with trisomy 18, but the
      abnormality may be subtle and or unilateral.

PMID- 9586708
TI  - Persistent abnormal umbilical cord Doppler velocimetry in a monoamniotic twin
      with cord entanglement.

PMID- 9586709
TI  - Laparoscopic adnexal ultrasonography: Technology in search of an indication.

PMID- 9586710
TI  - Transmission blocks for lower neck and inguinal lymph node radiotherapy.
AB  - We evaluate techniques for radiotherapy to low neck and inguinal lymph nodes.
      Partial transmission blocks (PTBs) simplify treatment planning, daily setup, and
      improve reproducibility and dose homogeneity. PTBs minimize the risk for dose
      misadministration to critical organs. Disadvantages include doses that are
      potentially lower to the medial cervical lymphatics and higher to the femur. PTBs
      can surmount common treatment planning problems.

PMID- 9586711
TI  - Dose profiles in the region of abutting photon and electron fields in the
      irradiation of head and neck tumors.
AB  - In the treatment of head and neck tumors, after excluding the spinal cord from
      the primary photon beam, en face electron fields are employed to boost the dose
      to the tissues overlying the spinal cord. The electron fields are "hot-matched"
      on skin with the posterior edges of the photon fields irradiating the primary
      tumor. The purpose of this study is to measure the dose distribution in the "hot"
      matched region between the photon and the en face electron fields. Using film
      dosimetry, we measured the dose distributions at depths of 1 cm and 3 cm in the
      junction of the abutting photon (4 MV) and electron (9 MeV) fields for a hot
      match setup. Two photon field setups were studied: (1) laterally opposed and, (2)
      shallow (5 degrees) right and left anterior oblique fields, a configuration
      sometimes used to avoid treating through the shoulders. To investigate the
      changes in dose distributions due to setup uncertainties, we also measured dose
      profiles at the same two depths using a 2 mm overlap and a 2 mm gap between the
      electron and photon fields. For a perfect hot-match, the dose profile across the
      junction at 1 cm depth consists of "hot-spots" on both sides of the junction. The
      minimum and maximum doses across the junction are 15% and 58%, respectively,
      above the prescribed dose for a parallel opposed setup and 35% and 54%,
      respectively, for the angled setup. At 3 cm depth, a 10% "cold spot" is observed
      in the electron field proximal to the junction while a 50% 'hot spot' is observed
      in the photon field for the opposed lateral setup. With the lateral fields angled
      5 degrees anteriorly, hot spots are observed on both sides of the junction. The
      minimum and maximum doses are 23% and 54%, respectively, above the prescribed
      dose. With the right and left anterior oblique fields, a 2 mm overlap of the en
      face electron field with the ipsilateral photon field resulted in a 72% and 65%
      hot spot at 1 cm and 3 cm depths, respectively, in the photon field adjacent to
      the junction. A 2 mm gap still resulted in about a 45% hot spot in the same
      region at both depths. Clinically, if dose to the overlying tissue of the spinal
      cord is of primary concern, our measurements suggest that 80% normalization in
      the electron boost, together with a slight angulation of the photon fields would
      ensure adequate dose to the overlying tissues. If dose inhomogeneity to the
      superficial tissues is critical in the electron irradiation, 90% dose
      normalization in the electron boost, together with laterally opposed photon
      fields would be preferred. The clinical decision can only be made on a patient-by
      patient basis.

PMID- 9586712
TI  - Head and neck compensation for total body irradiation using opposed laterals.
AB  - Using shaped brass compensators that follow the coronal profile of a patient's
      head and neck, we confirm that adequate compensation can be made to prevent
      overdosing in these regions when delivering total body irradiation using opposed
      lateral fields. Initially, these compensators were custom made for each patient,
      but we have shown that the variation from patient to patient is sufficiently
      small that individual compensators can be used for a number of different patients
      without compromising the dose distribution. In a subgroup of 35 patients on whom
      diode measurements were made, 20 used compensators from the library of
      approximately 40 compensators made for previous patients and 15 required new
      compensators to be fabricated. No significant difference (3.4% on average) was
      observed in the dose distribution. By examining the profiles accumulated from 81
      patients, we have shown that the primary difference between patients is not in
      the shape of the head and neck, but in the distance from the top of the head to
      the suprasternal notch and in the slope of the shoulders; thus, shaped
      compensators are not necessary and the same quality of dose homogeneity can be
      achieved using simple flat brass plates. Further, if the arms are supported so
      that the slope of the shoulders is constant, a relatively small number (15) of
      square-ended plates of thickness ranging from 4.0 to 11.0 mm would be sufficient
      to treat all 81 patients in our sample.

PMID- 9586713
TI  - Tangential irradiation of the intact breast: the ABC of the technique.
AB  - This paper describes in detail the setup of breast irradiation using an
      isocentric tangential technique. This setup method does not require any special
      devices or calculations beyond simple arithmetic. We will discuss some of the
      practical problems and pitfalls that result from the oblique incidence of the
      radiation beams and the slope of the chest wall and provide possible solutions.

PMID- 9586714
TI  - Tin shielding thicknesses for electrons.
AB  - The transmission of 6, 9, 12, 16, and 20 MeV electrons from a linear accelerator
      through tin and lead is studied at 0.5 cm depth in polystyrene. These
      measurements are performed using a 10 x 10 cm2 cone and extend well into
      bremsstrahlung region. The results show certain advantages of using tin to shield
      sensitive organs from electron beams. Tin is non-toxic and creates less
      additional bremsstrahlung even though it must be thicker than the equivalent lead
      shield.

PMID- 9586715
TI  - An alternative buildup material: combine dressing and liquid paraffin.
AB  - A tissue substitute of combine dressing (gauze and cottonwool) soaked with liquid
      paraffin was found to be a practical, easily manufactured and inexpensive buildup
      material for use in treating radiation therapy patients with electron and photon
      beams. Tissue equivalence was measured for electron energies of 6, 9, 12, and 16
      MeV and photon energies of 6 MV and 10 MV delivered by a Varian 2100C linear
      accelerator. The solid water equivalence of the combine dressing/liquid paraffin
      material was approximately 1.2 times the geometric thickness of tissue substitute
      material across all energies.

PMID- 9586716
TI  - Modification of a linear accelerator table top for non-coplanar conformal brain
      radiotherapy.
AB  - The use of non-coplanar conformal therapy necessitates the use of unusual beam
      projections that may not be accomplished with a conventional linear accelerator
      table top. Modification of the table top can increase the available combinations
      of gantry and couch rotation. A standard Philips table top, supplied with an SL
      75-5 linear accelerator, was modified to increase available combinations of
      gantry and couch rotation. This was accomplished by shortening the length and
      decreasing the width of the table top. The modified table top increases the
      combinations of gantry and couch angles significantly, simplifying the delivery
      of non-coplanar conformal therapy without significant compromise to routine
      treatment. The modification of a standard linear accelerator table top has
      increased the available combinations of gantry and couch rotation to accommodate
      non-coplanar conforrmal radiotherapy.

PMID- 9586717
TI  - Measurement of radiation dose delivered to breast tissue during mantle field
      irradiation for Hodgkin's disease.
AB  - The treatment of Hodgkin's disease involves mantle field irradiation. Patients
      with early stage (I-II) Hodgkin's are often in their 20's or 30's and can expect
      to live for many decades after the successful management of their disease;
      however, complications, including second cancers in the treatment area, occur in
      some survivors. Breast cancer is among the leading second solid cancers that
      develop in patients who have undergone mantle field irradiation. This paper
      attempts to determine the dose that may be delivered to breast tissue from mantle
      field irradiation to treat Hodgkin's disease. Utilizing an anthropomorphic
      phantom, thermoluminescent dosimeters (TLDs) were placed into a breast phantom
      constructed of Superflab and TX-150, and were irradiated with 6 MV photons.
      Readings from 170 TLDs in five layers of breast phantom were analyzed. The
      results show considerable doses reaching portions of breast tissue. In measured
      points under the blocks, 8-15% of the prescribed isocenter dose was delivered.
      For points in the primary beam, readings of up to 91% of the isocentric dose were
      obtained. Points in the breast near block or collimator edges also received
      substantial doses; upwards of 70% of the prescribed dose. Several points in the
      breast outside the treatment field were also measured and readings ranged from 2
      to 29% of the prescribed dose. Similar patterns of dose distribution were found
      on computer plans; however, point-by-point comparisons were not performed. These
      results are compared with published reports.

PMID- 9586718
TI  - Use of radiochromic dosimetry film for HDR brachytherapy quality assurance.
AB  - An important quality assurance (QA) procedure in high dose rate (HDR) remote
      afterloading brachytherapy is the verification of the system's control of the
      source by a direct test with dosimetry medium prior to the patient's first
      treatment. In this test radiochromic film is placed in direct contact with the
      applicator and the patient's proposed treatment is then run with their EPROM
      card. Examination of the film allows a quick appraisal of step size, number of
      steps, and offset. Advantages of this film include self-development so the image
      may be viewed immediately, insensitivity to normal room light, and archivability.
      The cost is about U.S. $2 per clinical case.

PMID- 9586719
TI  - Dosimetric aspects of small circular fields of 10 MV photon beam.
AB  - Dosimetric data obtained from different measurement techniques of 10 MV small
      circular photon beams of 12.5, 20, 30, and 40 mm diameter were studied. The
      effects of lack of lateral electronic equilibrium and steep dose gradient were
      noticed even when measurements were performed with a small volume (0.02 cc)
      ionization chamber. From an examination of the results, it is concluded that an
      average value of data obtained from several carefully performed film measurements
      may be used for routine radiosurgery.

PMID- 9586720
TI  - A standardized form for weekly check of therapy charts.
AB  - A form for the weekly physics check of therapy charts by the Physics staff has
      been developed. It is found to be a time saving and quality improvement tool.

PMID- 9586721
TI  - A simple oral cone attachment for the Varian linear accelerator.
AB  - Lesions in the oral cavity are often treated with two opposed lateral fields.
      These include a significant amount of normal healthy tissue whose radiation
      tolerance is dose-limiting. The tumor dose can be boosted to tumorcidal levels by
      brachytherapy or by small electron fields directed straight on the lesion. We
      have developed a simple attachment to the standard electron applicator of the
      Varian Clinac 1800 that allows irradiation of small electron fields through
      acrylic tubes-the oral cones. These tubes have been evaluated in terms of depth
      dose and field profiles for 6, 9, 12, 16, and 20 MeV electrons using film for
      relative dosimetry. At these small field sizes there are significant changes in
      output factors, in the depth dose as well as in the effective size of the field,
      and a thorough dosimetric evaluation is imperative prior to treatment. The
      attachment can be manufactured locally at low cost. For reasons of patient safety
      the assembly is collapsible. In clinical practice the cone is directed directly
      on the tumor. For deep-seated lesions we use a penlight and a mirror for
      positioning.

PMID- 9586722
TI  - A comparison of measured and calculated output for highly blocked photon fields.
AB  - The present work measured the accuracy of VAX monitor unit calculations currently
      used for highly blocked photon fields at The University of Texas M. D. Anderson
      Cancer Center. The VAX program is an in-house computer program that calculates
      the setting for linear accelerator photons that is needed to deliver a prescribed
      dose to a muscle miniphantom located on the beam's central axis at a prescribed
      depth beneath the surface in water. Monitor unit settings were computed for the
      Varian 2100 with multileaf collimation using 6 MV and 18 MV photons at a depth of
      10 cm with different blocking ratios. Concentric and lateral blocking methods
      were used. Measurements were taken with an ion chamber and then compared with the
      VAX calculations with off-axis factors and peak scatter factors added in that are
      not available in the program. The results showed less than 2% difference for the
      concentric fields containing no more than 80% blocking and an equivalent square
      of at least 3.5 cm for 6 MV and 5 cm for 18 MV X-rays. For the lateral fields
      with the central axis blocked, less than 2% difference was found when blocking
      was 80% or less and the equivalent square was no less than 3.5 cm for 6 MV X
      rays. For 18 MV X-rays, the maximum blocking and minimum equivalent square were
      60% and 5 cm for 2% accuracy. This confirmed that the VAX system currently in use
      is accurate unless a very large amount of blocking is present or the central axis
      is blocked in very small fields. Previous research done at dmax with similar
      blocking ratios produced similar results.

PMID- 9586723
TI  - Dose variation due to differences in applicator placement used for intracavitary
      brachytherapy of cervical cancer.
AB  - The prognosis for women with early stage cancers of the cervix is excellent. The
      cervix and proximal vagina are relatively radioresistant structures; dose
      limiting critical structures for radiation treatment in this area are tissues
      such as the bladder and rectum. The high dose rate gradient of brachytherapy
      allows high doses to the tumor volume, while doses to the neighboring structures
      are lower. Intracavitary treatment of cervical cancer is performed by insertion
      of tandem and ovoid applicators. Correct tandem and ovoid placement is verified
      and documented with orthogonal radiographs. If placement of the tandem and ovoid
      is not acceptable, the packing is removed, and the tandem or ovoid is
      repositioned or exchanged as necessary. To examine the difference in dose to
      specific reference points when tandem or ovoid placement was changed by the
      physician, three patients' initial insertion radiographs were compared to those
      that were accepted to treat. Points of comparison selected for the patients on
      each of the insertions were: point A (L and R), external iliac nodes (L and R),
      bladder, and rectum. Each of the placement changes for the three patients
      resulted in differences in distance, and therefore, differences in dose. Changes
      as high as 823 cGy resulted from the adjustment of only one component. In the
      cases examined, repositioning improved dose distribution to the cervix, and
      lowered the dose to adjacent critical structures.

PMID- 9586724
TI  - A code of ethics for the medical dosimetrist--the American Association of Medical
      Dosimetrists experience.
AB  - The Committee on Protocol and Ethics of the American Association of Medical
      Dosimetrists (AAMD) has developed a Code of Ethics for a radiation oncology
      society of medical dosimetrists. The purpose of the code of ethics is fourfold:
      (1) Establish an ideal of professional conduct specific to the medical dosimetry
      profession; (2) Develop a statement of the moral values and commitment of the
      AAMD; (3) Recognize professional relationships and obligations; and (4) Define
      goals to which the medical dosimetrist should aspire. The Code of Ethics was
      adopted as AAMD policy in October 1995.

PMID- 9586725
TI  - Patellofemoral arthrosis: the treatment options.
AB  - Patellofemoral arthritis is a relatively common and frequently complex problem
      encountered by those who treat patients with anterior knee pain. Because the
      pathologic conditions that precipitate this pain are so varied, the treatment
      options must also be varied. Using the Insall classification system for chondral
      injuries, we explored the treatment options available. Special emphasis was
      placed on grade IV changes and the surgical treatment of this condition. We
      reviewed the following options: spongialization, tibial tubercle elevation,
      patellectomy, patellar resurfacing, patellofemoral arthroplasty, and autologous
      chondrocyte transplantation. Regardless of the procedure favored, proper patellar
      tracking must be restored. Without such attention to patellar alignment, patients
      cannot achieve pain-free function.

PMID- 9586726
TI  - Advances in total hip arthroplasty.
AB  - Total hip arthroplasty is an operative procedure in which the diseased and
      destroyed hip joint is resected and replaced with a new bearing surface. Since
      its introduction into the surgical management of the arthritic hip in the early
      1960s, total hip arthroplasty has helped alleviate the suffering of millions of
      patients throughout the world. Patients with coxarthrosis can now look to total
      hip arthroplasty as a reliable means of pain relief and improved function. While
      the operation has been successful over the years, problems have manifested
      themselves as the length of follow-up has increased. As total hip arthroplasty
      approaches its fourth decade of use, we outline these problems and the proposed
      solutions.

PMID- 9586727
TI  - Hard bearing surfaces in total hip arthroplasty.
AB  - Periprosthetic osteolysis and aseptic loosening are serious problems affecting
      the outcome of total joint replacement. Polyethylene particulate debris generated
      from metal-on-polyethylene bearing surfaces and the resulting biologic response
      to this debris are thought to be largely responsible. As a result, there has been
      a renewal of interest in hard bearing surfaces for total joint arthroplasty,
      including both metal-on-metal and ceramic-on-ceramic components. The new
      generation all-ceramic and all-metal prostheses have demonstrated, both
      clinically and in the laboratory, lower friction and wear rates than metal-on
      polyethylene bearing surfaces. Theoretically, lower wear rates result in less
      particulate debris and decreased inflammatory response. Despite excellent
      tribologic (lubrication, friction, wear) properties, metal-on-metal bearings
      raise associated issues of metal sensitivity and toxicity. For ceramic-on-ceramic
      bearing surfaces, issues of ceramic quality and the possibility of brittle
      fracture must be considered.

PMID- 9586728
TI  - Maximizing cost-effectiveness while minimizing complications in total hip
      replacement.
AB  - Between July 1989 and June 1994, a consecutive series of 651 cemented total hip
      arthroplasties were performed in 577 patients using relatively inexpensive
      implants and standardized surgical and postoperative protocols. We set out to
      determine what effect these cost-saving measures have on the overall success and
      complication rate after total hip replacement surgery. Surgical results remained
      excellent, and perioperative, early, and late complications, including infection,
      loosening, and revision hip surgery, remained minimal, indeed, below usual
      complication rates. We concluded that cost-effective measures can be implemented
      while maintaining the overall excellent results of hip replacement surgery
      without the risk of increasing complication rates.

PMID- 9586729
TI  - Deep venous thrombosis prophylaxis for knee replacement: warfarin and pneumatic
      compression.
AB  - A prospective study of the prevalence of proximal deep venous thrombosis in total
      knee replacement patients who had prophylaxis for thrombosis with a combination
      of low-dose warfarin and intermittent pneumatic compression was done. Two hundred
      and ninety-seven patients who underwent 377 consecutive total knee replacements
      were studied. All patients were treated with low-dose warfarin and intermittent
      pneumatic compression using thigh-high sleeves. Surveillance for proximal
      thrombosis was done by duplex ultrasonography. Proximal thrombosis was detected
      in 19 patients, for a prevalence of 5%. There were 3 patients who had a major
      bleeding complication, for a prevalence of 0.9% for the 337 procedures performed.
      Although there was no concurrent control group of patients treated with another
      means of prophylaxis to compare with these patients, the low prevalence of
      proximal thrombosis and the low risk of major bleeding complications that was
      found compares well with recent reports on the effectiveness and safety of low
      molecular-weight heparin.

PMID- 9586730
TI  - Overgrowth of the ischial tuberosity complicating femoral bone and muscle
      atrophy: implications for a delayed complication of malunited apophyseal avulsion
      fracture.
AB  - Delayed complications occurring several years after the fused avulsion of ischial
      tuberosity have rarely been reported. We present a patient with overgrowth of the
      ischial tuberosity who complained of knee pain associated with significant bone
      and muscle atrophy in the thigh, which occurred 10 years after the ischial
      injury. Reinforcement exercise of the hamstrings relieved the knee pain. Here, we
      emphasize that avulsion fractures of the ischial tuberosity can cause persistent
      disability and that patients with avulsion fracture of the ischial apophysis in
      the adolescent period should actively maintain the strength of the hamstrings,
      even after more than 1 decade.

PMID- 9586731
TI  - Multiple dorsal dislocations of the metacarpophalangeal joints: a case report and
      review of the literature.
AB  - A case of multiple dorsal dislocations of the metacarpophalangeal joints is
      presented with a review of literature. Prompt recognition of the dislocation type
      is essential, followed by trial of closed reduction under proper anesthesia; open
      reduction is sometimes required. A short period of immobilization is needed,
      followed by intensive rehabilitation.

PMID- 9586732
TI  - Train accidents involving pedestrians, motor vehicles, and motorcycles.
AB  - In the United States, train-related accidents account for more than 18,000
      injuries and 1,200 fatalities annually, yet there is a paucity of literature
      pertaining to this unique injury. We reviewed the medical records of 98 of 135
      cases of train-related trauma treated at Ben Taub General Hospital, Baylor
      College of Medicine, Houston, Texas, from 1990 to 1995. There were 50 train
      pedestrian accidents, 47 train-automobile accidents, and 1 train-motorcycle
      accident, with a mean patient age of 30.1 years (range, 2 to 66 years). Eighteen
      patients (18%) were pronounced dead on arrival or died shortly after admission.
      Of the other 80 patients, 27 (34%) were discharged from the emergency department
      after minor medical treatment, while 53 (66%) were hospitalized, of whom 10 (13%)
      later expired. The mean Injury Severity Score (ISS) was 11.9 (discharged, 1.8;
      hospitalized, 14.3; expired, 29.2). Forty-five patients (56%) sustained 57
      extremity fractures, and 30 patients (38%) required 40 amputations. Mean Mangled
      Extremity Severity Score (MESS) for all injured extremities was 5.2 (amputation,
      7.7; no amputation, 2.8). On average, the hospitalization cost per patient was
      greater than $18,698, while the reimbursement from the patients was $2,261,
      leaving the hospital with a net deficit of approximately 2 million dollars.
      Surprisingly, train accidents do not always result in serious injury. However,
      when serious injury is sustained, it is often of high morbidity (amputation) and
      mortality, which appears to correlate well with the initial MESS and ISS.
      Extrapolating our cost data to include all train-related accident injuries and
      deaths indicates that the direct costs to society may exceed 300 million dollars
      annually. Greater public awareness and preventive measures may reduce the
      tremendous human and financial costs of train-related accidents.

PMID- 9586733
TI  - The LineFinder: a new method for finding the bone center line and femoral head
      center point.
AB  - A plastic template-type device with a central slot is described. This device
      allows rapid identification of the center line of long bones and the center point
      of femoral heads.

PMID- 9586734
TI  - ACL surgery: evolution under control.

PMID- 9586735
TI  - Knee implant standardization: an implant selection and cost reduction program.
AB  - The largest single unit cost in the hospital cost for total knee arthroplasty
      (TKA) is the cost of knee implants. We developed a knee implant standardization
      program to provide guidelines for knee implant selection and to reduce the cost
      of knee implants for hospitals. Patients are assigned to demand categories based
      on five criteria: age, weight, expected activity, general health, and bone stock.
      Implants are assigned to demand categories based on an implant's projected
      capacity to handle the patient's projected demand. The program was applied
      retrospectively to 127 knee replacement operations performed on 93 patients
      during 1992. If this program had been in place, 8.4% of what was actually spent
      on knee implants for these 127 patients would have been saved. If the most
      expensive implants allowed in each demand category had actually been used, the
      program would have saved our hospital 12.8% of the cost of knee implants for
      these patients. Potential savings were noted in higher demand categories I and II
      by reducing the use of expensive cementless, porous-coated implants. The greatest
      potential savings were noted in lower demand categories III and IV: 11% savings
      could have been realized in demand category III, and 27% savings could have been
      achieved in the cost of knee implants in demand category IV. Potential savings
      would have been realized in these lower demand categories because of the
      recommended use of an all-polyethylene tibial component in 38 of 92 patients.
      This knee implant standardization program has the potential to assist surgeons in
      selecting knee implants and reduce the cost of knee implants without compromising
      outcome following TKA.

PMID- 9586736
TI  - Intercondylar notch encroachment following anterior cruciate ligament
      reconstruction: a prospective study.
AB  - Intercondylar notch impingement is a recognized cause of graft failure following
      anterior cruciate ligament (ACL) reconstruction and typically is attributed to
      anterior tibial tunnel placement or inadequate notchplasty. This prospective
      study assessed the incidence and nature of notch regrowth following initial ACL
      reconstruction. The study population was comprised of 36 patients who underwent
      ACL reconstruction using a patellar tendon-bone autograft. A 3- to 5-mm
      notchplasty was performed in all patients, and an intraoperative radiograph was
      taken confirming proper tunnel placement. Magnetic resonance imaging (MRI) was
      performed the first week following surgery and again at 6 months. The MRIs were
      reviewed by two skeletal radiologists to evaluate postoperative notch and graft
      changes. Of the 36 study patients, 28 (78%) knees showed no evidence of graft
      impingement as defined by graft indentation and intra-substance edema. The MRIs
      of 8 (22%) patients showed evidence of graft impingement. Four patients had
      clinical signs of graft impingement, namely persistent effusion or lack of full
      extension. Arthroscopically, 3 of these patients demonstrated graft encroachment
      and impingement by fibrocartilage with areas of immature bone. These results
      indicate that graft impingement from regrowth of the notch is a clinically
      relevant phenomenon that could potentially result in late graft demise in the ACL
      reconstructed knee.

PMID- 9586737
TI  - Postoperative radiographs after total knee arthroplasty: a cost-containment
      strategy.
AB  - We reviewed a single surgeon's experience with 646 consecutive total knee
      arthroplasties (TKAs) performed over a 6-year period to determine whether routine
      in-hospital radiographs could be safely avoided. Five hundred fourteen patients
      underwent 589 primary and 57 revision TKAs. One hundred thirty-two patients had
      bilateral procedures. Radiographs were obtained during the index hospitalization
      for 12 (2%) knees and were ordered selectively to assess femoral notching > or =3
      mm, concomitant osteotomy, bulk allograft reconstruction, stem extension relative
      to existing hardware or screw holes, or falls during the index hospitalization.
      Radiographs were delayed until the initial postoperative office visit for the
      remaining 634 (98%) knees. Six hundred seventeen of 646 knees (96%) were
      evaluated at a mean follow-up of 4.3 years (range: 2 to 8 years). No patient
      experienced any complication that was considered to be attributable to not
      obtaining earlier postoperative radiographs. Three patients experienced late
      fractures and 7 patients developed perioperative soft-tissue complications or
      infections. None of these cases were adversely affected by delaying the initial
      postoperative radiographs. Eliminating in-hospital radiographs with radiologist
      interpretation resulted in a potential savings of $246 in hospital charges, $198
      in private insurance reimbursements, and $65 in hospital costs per TKA. These
      findings indicate that radiographs following TKA can be delayed in most cases
      until the first postoperative office visit without compromising patient care.

PMID- 9586738
TI  - Hemarthrosis as a major complication after arthroscopic subcutaneous lateral
      retinacular release: a prospective study.
AB  - The use of arthroscopic lateral release and medial imbrication of the vastus
      medialis obliquus for recurrent dislocation of the patella was evaluated
      prospectively in 31 patients. Patients were examined clinically as well as
      radiologically; the average length of follow-up was 34.4 months. Seventy-one
      percent of the patients were satisfied with the operative result. Seven patients
      experienced redislocation of the patella. Postoperative effusion occurred in 13
      (42%) patients, with 4 patients requiring aspiration and 3 patients requiring
      open revision because of hemarthrosis. Seven patients developed a long-lasting
      stiffness of the joint following a 3-week period of immobilization with a dorsal
      plaster splint of the whole leg.

PMID- 9586739
TI  - Hamstring and patellar tendon graft response to cyclical loading.
AB  - This study evaluates the effect of submaximal cyclical loads on the tendinous
      portion of the central 10 mm of the patellar tendon compared with doubled
      semitendinosus and gracilis tendons. Six fresh-frozen cadaveric knee specimens
      were used for the study. There was no significant difference between the cross
      sectional areas of a 10-mm patellar tendon and four strands of hamstring tendon
      (looped semitendinosus and gracilis) from the same specimen. The mean cross
      sectional area was 44.4 mm2 for the patellar tendon and 47.5 mm2 for the four
      strands of hamstring. The specimens were cyclically loaded for 1000 cycles from 0
      to 300 N at a rate of 1 Hz; the materials testing machine was set on load
      control. There were no significant differences in the strain, stress, or modulus
      between the 10-mm patellar tendon and four strands of hamstring tendon after 1000
      cycles of loading to 300 N. These data substantiate the excellent clinical
      results obtained with either graft source and support the use of either graft
      source for ACL reconstruction.

PMID- 9586740
TI  - Total knee arthroplasty after Hauser procedure: case report.

PMID- 9586741
TI  - Genu recurvatum deformity secondary to partial proximal tibial epiphyseal arrest:
      case report.

PMID- 9586742
TI  - Preemptive pain management program for anterior cruciate ligament reconstruction.

PMID- 9586743
TI  - Aggressive rehabilitation using hamstring tendons: graft construct, tibial tunnel
      placement, fixation properties, and clinical outcome.

PMID- 9586744
TI  - The evolution and current treatment trends with anterior cruciate, posterior
      cruciate, and medial collateral ligament injuries.

PMID- 9586745
TI  - Controversies with anterior cruciate ligament surgery and rehabilitation.

PMID- 9586746
TI  - Outcomes research--translating efficacy into effectiveness.

PMID- 9586748
TI  - Oblique astigmatism of the Indiana eye.

PMID- 9586747
TI  - Monitoring drug safety; cardiac events in routine mydriasis.

PMID- 9586749
TI  - Visual acuity repeatability in keratoconus: impact on sample size. Collaborative
      Longitudinal Evaluation of Keratoconus (CLEK) Study Group.
AB  - PURPOSE: The purpose of this paper is to determine the repeatability of visual
      acuity measurement in keratoconus and to describe the impact of measurement
      repeatability on sample size. METHODS: Approximately 10% of a 1209 patient sample
      in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study were
      selected randomly for a Repeat CLEK Study Visit. Patients were tested at the 15
      CLEK Participating Clinics. The test-retest sample consisted of 1 34 keratoconus
      patients who met the entry criteria of the CLEK Study. High and low contrast
      Bailey-Lovie visual acuity was measured with the patient's habitual visual
      correction (entrance visual acuity monocularly and binocularly), and with the
      best correction monocularly (either the patient's rigid contact lens and over
      refraction, or with a CLEK Study trial lens and appropriate over-refraction) at
      two visits separated by a median of 90 days (range 22 to 268 days). RESULTS: The
      mean absolute differences between the number of letters correct at the two visits
      ranged from a low of 3.24 +/- 3.1 for entrance high contrast binocular acuity to
      a high of 5.48 +/- 5.1 for best corrected low contrast monocular acuity.
      Intraclass correlation coefficients ranged from 0.757 to 0.853. The visual acuity
      score was somewhat higher at the Repeat Visit than at the Baseline Visit when the
      examiners were different between visits. CONCLUSIONS: Given the variable vision
      reported by keratoconus patients, visual acuity in this sample was very
      repeatable. Repeatability was slightly poorer when different examiners tested
      visual acuity at the Baseline and Repeat Visits.

PMID- 9586750
TI  - Identification and enumeration of staphylococci from the eye during soft contact
      lens wear.
AB  - PURPOSE: An extensive study was conducted to identify and enumerate
      staphylococcal microbiota found on ocular sites during asymptomatic soft contact
      lens (SCL) wear. METHODS: A biochemical identification system separately grouped
      the eight clinically relevant staphylococci. Total counts and isolation
      frequencies from SCLs and ocular sites were evaluated. RESULTS: The epidermidis
      group was the most numerous isolate from extended wear (EW) lenses; the
      capitis/warneri group was the most numerous (p < 0.05) from daily wear (DW)
      lenses. In both DW and EW, the greatest isolation frequency (p < 0.05) was
      recorded for the capitis/warneri group. The remaining six groups were isolated
      infrequently and in low numbers. DISCUSSION: These results show that, in addition
      to Staphylococcus epidermidis, other staphylococcal species may be important
      members of the normal microbiota of the ocular surface during SCL wear.
      Furthermore, an increase and a shift in staphylococcal microbiota between DW and
      EW regimes was highlighted.

PMID- 9586751
TI  - Interactions of bacteria with contact lenses: the effect of soluble protein and
      carbohydrate on bacterial adhesion to contact lenses.
AB  - PURPOSE: During contact lens wear, components in the tear film adsorb to the
      contact lens surface to form a protein-rich coating. In this study, we
      investigated the importance of these components in bacterial adhesion to contact
      lenses. METHODS: Five strains of bacteria were tested for their ability to adhere
      to contact lenses (patient-worn; coated with lactoferrin, lysozyme, or an
      artificial tear formulation; or left uncoated) in the presence of various solutes
      (protein, carbohydrate). Bacterial adhesion was quantified by both a total count
      (light microscopy) and viable count (culturing on agar). RESULTS: None of the
      solutes were found to competitively inhibit bacterial adhesion to worn contact
      lenses. However, lactoferrin was observed to kill bacteria attached to worn
      contact lenses. CONCLUSIONS: We could find no evidence to indicate that bacterial
      adhesion to contact lenses is mediated by specific interactions between bacteria
      and contact lens-bound tear components. The interaction between attached bacteria
      and lactoferrin may be important in initiating inflammatory responses to contact
      lens wear.

PMID- 9586752
TI  - A comparison of low vision clinic data with low vision survey and blindness
      registration information.
AB  - PURPOSE: To determine whether low vision demographic data provided by low vision
      clinic data are comparable to that provided by blindness registration and
      disability questionnaire information. METHODS: Low vision demographic data for
      Canada and Ontario within the postcensus Health and Activity Limitation Survey
      (HALS 1991) were obtained from Statistics Canada. These data were compared with
      4744 reports of low vision examinations obtained in a multi-center low vision
      clinic study in Ontario, Canada (1991-1994) and appropriate annual figures from
      the Canadian National Institute for the Blind (CNIB). RESULTS: Data from the low
      vision clinic study and the CNIB were similar. The low vision clinic study (and
      CNIB) reported far fewer adults (15 to 64 years) and far more seniors (65+ years)
      obtaining low vision examinations than suggested by HALS. CONCLUSIONS: HALS does
      not report on patients with low vision, as defined in low vision clinics. The
      differences between survey, low vision clinic, and blindness registration data
      are presented.

PMID- 9586753
TI  - Effect of luminance on visual evoked potential amplitudes in normal and disabled
      readers.
AB  - BACKGROUND: Considerable evidence exists that some reading-disabled children have
      disordered visual processing, specifically in the fast processing magnocellular
      (M) pathway. METHODS: The extent that varying luminance and temporal frequency
      affect amplitude and latency of visual evoked potentials (VEPs) in normally
      achieving and reading-disabled children grades 4 to 6 was measured. Each group
      consisted of approximately 30 subjects. Monocular and binocular single channel
      VEPs were recorded using a sinusoidal checkerboard pattern of spatial frequency
      14 min arc at 3 different temporal frequencies (1, 4, and 8 Hz), and an 8 Hz
      flicker fusion stimulus. Stimuli were presented under high and low luminance
      conditions. The peak of the major positive wave component (P100) of each waveform
      and the trough of the previous major negative wave component were identified, and
      the peak to trough amplitude was measured. RESULTS: Statistical analysis of the
      VEP amplitudes and latencies in response to different experimental conditions was
      performed using a repeated measure analysis of variance (MANOVA). VEP amplitudes
      were significantly higher for normal readers across all conditions. Within all
      subjects, significant effects were found for monocular vs. binocular viewing,
      temporal frequencies, and high vs. low luminance. Similar analysis of latencies
      revealed no significant differences. CONCLUSIONS: The presence of a weaker VEP
      response in reading-disabled children suggests a deficit early in visual
      processing. The significant difference in VEP amplitudes between the two reading
      groups provides an objective measure of a deficit in the M pathway that has been
      implicated in this condition. Whether serial VEP recordings might help to assess
      the effects of optometric therapy by providing an independent index of
      therapeutic efficiency is of special interest.

PMID- 9586754
TI  - Relationship between visual skills and performance on saccadic eye movement
      testing.
AB  - The effect of visual skills, such as binocularity, on saccadic eye movement test
      performance is currently unknown. Therefore, the relationship between performance
      on commonly used clinical saccadic eye movement tests and visual skill was
      studied in a masked investigation of 181 kindergartners and first graders (mean
      age 6.25 years) from a middle class, suburban, elementary school near Cleveland,
      Ohio. The New York State Optometric Association King-Devick saccade test (NYSOA K
      D) and the Developmental Eye Movement test (DEM) were employed because they are
      two commonly used clinical saccadic eye movement tests. A Modified Clinical
      Technique (MCT) vision screening and Randot stereoacuity test were performed to
      evaluate other visual skills. Analysis revealed that for the whole study
      population, total errors on the NYSOA K-D were significantly related to referral
      on the MCT screening (p = 0.015) and stereoacuity worse than 100 sec arc (p =
      0.011). A trend toward significance was also found between DEM ratio and
      stereoacuity worse than 50 sec arc for the whole study population. However, in
      the children who passed the MCT, stereoacuity was not found to be significantly
      related to performance on NYSOA K-D or DEM. Thus, our findings indicate that
      visual difficulties may affect performance on the NYSOA K-D in this population.

PMID- 9586755
TI  - Facial measurements for frame design.
AB  - Anthropometric data for the purpose of spectacle frame design are scarce in the
      literature. Definitions of facial features to be measured with existing systems
      of facial measurement are often not specific enough for frame design and
      manufacturing. Currently, for individual frame design, experienced personnel
      collect data with facial rules or instruments. A new measuring system is
      proposed, making use of a template in the form of a spectacle frame. Upon fitting
      the template onto a subject, most of the measuring references can be defined.
      Such a system can be administered by lesser-trained personnel and can be used for
      researches covering a larger population.

PMID- 9586756
TI  - Ophthalmic anthropometry for Hong Kong Chinese adults.
AB  - A database of ophthalmic anthropometry is established which is useful for the
      design of spectacles for southeast Asian people. Statistical analysis reveals
      significant variations in the facial dimensions between male and female subjects.
      Results of the study are given separately for each sex and for the combined
      population. Hong Kong Chinese are found to have larger frontal angles, bigger
      angles of splay, and a less prominent bridge in the nose. Spectacle frames should
      be designed according to the targeted gender population, and to accommodate the
      characteristics of Asian faces.

PMID- 9586757
TI  - The effect of intestinal permeability on pancreatic enzyme-induced enteropathy in
      the rat.
AB  - BACKGROUND: Fibrosing colonopathy in cystic fibrosis occurs in children 2 to 7
      years old and is associated with excess doses of high and regular strength lipase
      pancreatic enzymes, given for more than 6 months. A rat model was developed to
      study the effects of excessive doses of pancreatic enzymes equivalent to those
      producing fibrosing colonopathy in cystic fibrosis patients. METHODS: Five groups
      of animals were studied after administration of different combinations of
      pancreatic enzymes, oleic acid, and reserpine. RESULTS: Pancreatic enzymes alone
      produced minimal damage to the intestine and none to the liver. Excessive doses
      of pancreatic enzymes in combination with agents that increased intestinal
      permeability (oleic acid, reserpine) were associated with intestinal eosinophilia
      and necrosis of the jejunoileal muscle layer and inflammatory nodules in the
      liver, which increased with duration of insult. CONCLUSIONS: Increased intestinal
      permeability potentiates damage to the intestine caused by excessive pancreatic
      enzyme dosage. It is a characteristic of cystic fibrosis that may increase
      vulnerability to fibrosing colonopathy.

PMID- 9586758
TI  - Celiac disease and Turner syndrome.
AB  - BACKGROUND: Short stature is one of the features of Turner syndrome and a form of
      presentation of monosymptomatic celiac disease. METHODS: The recognition of
      celiac disease in two antiendomysium antibody-positive Turner syndrome girls who
      did not respond to growth hormone treatment led us to perform as a screening for
      celiac disease IgA and IgG antigliadin antibodies and antiendomysium antibodies
      determination in other 35 Turner syndrome patients. Intestinal biopsy was
      proposed to the antiendomysium antibodies-positive girls; in the former, subtotal
      villous atrophy was found; in the latter, one parent's consent for intestinal
      biopsy was not obtained. RESULTS: The prevalence of celiac disease in Turner
      syndrome patients observed in the present study (8.1 if we consider 3 villous
      atrophy, 10.8 if we consider 4 antiendomysium antibody-positive) is quite high
      and seems to indicate that the association of these two disorders could not be
      coincidental. As to the clinical picture, celiac disease appeared atypical in one
      case, typical in another one and as a silent form in the third case. Of the 3
      cases with villous atrophy on gluten-free diet growth hormone therapy was not
      effective in two girls, who were older than 16 years, while in the younger
      patient, detected by the screening, a significant increment of height velocity
      and height Standard Deviation Score for Chronological Age according to Turner
      references was observed. CONCLUSIONS: This study suggests that celiac disease can
      be associated with Turner syndrome and even responsible for a failure of growth
      hormone therapy. Therefore we propose to perform in Turner syndrome patients
      antiendomysium antibody determination as a screening followed by intestinal
      biopsy in positive cases. This would be advisable at least before starting growth
      hormone treatment.

PMID- 9586759
TI  - Serum leptin in children and young adults with inflammatory bowel disease.
AB  - BACKGROUND: Pediatric inflammatory bowel disease is often associated with growth
      failure and inadequate energy intake. Although several circulating cytokines are
      known to be elevated in inflammatory bowel disease, the mechanism for the related
      anorexia has not been described. Leptin is a newly recognized circulating protein
      that is an important regulator of appetite and energy metabolism; leptin levels
      are elevated in several animal models of inflammation. This study was conducted
      to determine whether serum leptin levels are elevated in young patients with
      inflammatory bowel disease. METHODS: One hundred twelve children and young adults
      with Crohn's disease or ulcerative colitis were studied prospectively. Forty-two
      patients with other gastrointestinal illnesses were used as control subjects.
      Height, weight, erythrocyte sedimentation rate, serum albumin concentration, and
      clinical information were collected prospectively, and leptin was measured by
      radioimmunoassay of stored serum. RESULTS: No significant differences in leptin
      levels were found among disease groups or control subjects. Body mass index and
      gender were the only independent predictors of serum leptin in all groups
      examined. Disease activity varied inversely with serum leptin in patients with
      Crohn's disease, but these differences were explained entirely by variations in
      body mass index. CONCLUSIONS: The determinants of serum leptin were the same in
      young patients with inflammatory bowel disease as in normal populations,
      indicating that alterations in leptin levels are unlikely to mediate the anorexia
      and growth failure associated with this disease.

PMID- 9586760
TI  - Epithelial growth of the small intestine in human infants.
AB  - BACKGROUND: Findings in studies in rodents have suggested that epithelial growth
      of the small intestine is dependent on activation of the immune system. The
      purpose of this study was to compare changes of postnatal epithelial growth with
      immunologic activity in humans. METHODS: Duodenal biopsies were obtained by
      endoscopy from 74 infants. Villus area, crypt length, and mitotic count were
      measured, using a microdissection technique. Enterocyte height, intraepithelial
      lymphocytes and mucosal mast cells were recorded in histologic sections, and
      soluble interleukin-2 receptor levels were measured in sera. These data were
      compared with those from 77 adult control subjects. RESULTS: Mean +/- SD villus
      area was similar in infants compared with that in adults (0.364 +/- 0.108 mm2 vs.
      0.339 +/- 0.1 mm2); but mean crypt length was 31% longer (270 +/- 56 microm vs.
      206 +/- 29 microm; p < 0.0001), and mitotic count was 68% higher (4.2 +/- 2.8 vs.
      2.5 +/- 1 per crypt; p < 0.0001) in infants. Enterocyte height was lower during
      infancy (27.0 +/- 3.4 microm vs. 30.9 +/- 4.6 microm; p < 0.0001). There was no
      evidence of a trophic effect on the small intestine of breast feeding compared
      with the effect of bottle feeding. Counts of intraepithelial lymphocytes but not
      mucosal mast cells were significantly less in infants. Mean soluble interleukin-2
      receptor levels peaked during early infancy, compared with levels in adults
      (1,820 +/- 596 U/ml vs. 695 +/- 359 U/ml). CONCLUSION: These results indicate
      that epithelial proliferation is increased during infancy at an age when
      immunologic activity is high.

PMID- 9586761
TI  - Efficacy of a glutamine-based oral rehydration solution on the electrolyte and
      water absorption in a rabbit model of secretory diarrhea induced by cholera
      toxin.
AB  - BACKGROUND: Glutamine is absorbed in the intestinal tract coupled with sodium and
      is the principal metabolic substrate for the enterocyte. Therefore, an oral
      rehydration solution containing this substance might provide an effective oral
      means of restoring electrolyte losses as well as speeding repair of mucosal
      damage. The objective of this work was to investigate the use of an oral
      rehydration solution based on glutamine in vivo in the perfused rabbit ileal loop
      model of secretory diarrhea induced by choleratoxin. METHODS:
      Phenolsulfonphthalein (PSP, 50 mg/l) was used as a nonabsorbable marker for
      calculations of net water and electrolyte transport. Solutions tested included:
      (a) a glutamine-based oral rehydration solution with 111 mmol/l glutamine, (Gln
      ORS); (b) the oral rehydration solution recommended by the World Health
      Organization; (c) modified Ringer's solution. Choleratoxin (1 microg/ml) was
      injected into the lumen of the ileal rabbit segments for 30 minutes prior to the
      initiation of the perfusion. RESULTS: Choleratoxin induced significant secretion
      of sodium in the control modified Ringer's solution (10.8 +/- 2.95 vs -14.05 +/-
      5.95 microEq/g/min, n = 10; p < 0.01) and of water (0.06 +/- 0.03 vs -0.15 +/-
      0.06 ml/g/min, n = 10; p < 0.01) with a maximum effect at 60 minutes after
      initiation of perfusion. World Health Organization oral rehydration solution was
      able to significantly reduce the intestinal secretion of sodium (control with
      cholera = -14.34 +/- 2.18 vs oral rehydration solution with cholera = -0.50 +/-
      0.48 microEq/g/min, n = 10; p < 0.01) and water (-0.15 +/- 0.02 vs -0.012 +/-
      0.005 ml/g/min, n = 10; p < 0.01). For comparison, glutamine-based oral
      rehydration solution had an even greater effect on sodium and water absorption
      (glutamine-based oral rehydration solution with choleratoxin = 10.31 +/- 1.21
      microEq/g/min, n = 5; p < 0.01 for sodium and 0.08 +/- 0.008 ml water/g/min; n =
      5; p < 0.01). Choleratoxin did not change the effect of glutamine-based oral
      rehydration solution on sodium and water absorption (12.90 +/- -1.09 microEq
      sodium/g/min, n = 5; and 0.11 +/- 0.01 ml water/g/min; n = 5). In addition
      glutamine-based oral rehydration solution also induced a greater absorption of
      potassium and chloride in the intestinal ileal segments treated with choleratoxin
      compared with World Health Organization glutamine-based oral rehydration
      solution. CONCLUSIONS: These results demonstrate the superior efficacy of
      glutamine-based oral rehydration solution in electrolyte and water absorption
      compared with modified Ringer's control solution or even with World Health
      Organization-recommended oral rehydration solution.

PMID- 9586762
TI  - Clinical quiz. Diffuse pseudomembranous colitis.

PMID- 9586763
TI  - Cellular microbiology: how enteric pathogens socialize with their intestinal
      host.

PMID- 9586764
TI  - Glutamine-based oral rehydration solutions: the magic bullet revisited?

PMID- 9586765
TI  - Evaluation of peri- and post-natal toxicity of Policosanol in rats.
AB  - The effects of Policosanol, a newly developmented hypocholesterolemic drug
      administered during the perinatal and postnatal periods, were studied in Sprague
      Dawley rats. This compound was administered orally to female rats at dose levels
      of 0 (control), 5, 50, and 500 mg/kg/day, from day 15 of pregnancy to day 21
      after parturition. The animals were allowed to deliver and their offspring were
      examined for postnatal growth and development. No signs of toxic effects related
      to the test material were observed in the dams F0 during pregnancy and lactation.
      No adverse effects were observed on the postnatal growth, behaviours, or
      reproductive ability of pups F1. The physical and sensorial development of pups
      F2 was also normal. These results confirm that Policosanol does not affect the
      reproductive performance or fetal/neonatal development.

PMID- 9586766
TI  - DNA damage in isolated rat hepatocytes exposed to C.I. pigment orange 5 and C.I.
      pigment yellow 12 by the alkaline comet assay.
AB  - The induction of DNA damage by commonly used printing ink pigments, C.I. pigment
      orange 5 (C.I. 12075) and C.I. pigment yellow 12 (C.I. 21090), was investigated
      in freshly isolated rat hepatocytes with the comet assay. C.I. pigment yellow 12
      is a 3,3'-dichlorobenzidine-based diarylide pigment, and C.I. pigment orange 5 is
      a naphthol-azo pigment. The pigments are virtually insoluble in aqueous
      solutions, and they have not been tested extensively for toxicological effects.
      C.I. pigment orange 5 increased the levels of DNA damage at 5 microg/ml (P <
      0.02) and C.I. pigment yellow 12 at 20 microg/ml (P < 0.002). The effect of
      incubation time (20, 40, and 80 min) of the same concentrations of the pigments
      was tested. The levels of DNA damage were increased up to 80 min. Both pigments
      produced DNA damage that was in the same range as the food carcinogen 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline. Our data indicate that both C.I. pigment
      orange 5 and C.I. pigment yellow 12 are genotoxic in hepatocytes with
      metabolizing capacities. However, further investigation of the metabolism and
      disposition are required for the evaluation of the safety of these pigments.

PMID- 9586767
TI  - AP endonuclease activity in humans: development of a simple assay and analysis of
      ten normal individuals.
AB  - The human AP endonuclease (APE) activity counteracts the mutagenic and cytotoxic
      effects of the frequent genomic lesions abasic (AP) sites. In order to
      investigate the interindividual variability of APE levels, a simple and
      quantitative assay was developed. Crude lymphocyte extracts were incubated with a
      depurinated or a control supercoiled plasmid substrate, and the accumulation of
      nicked circular plasmid forms was monitored by agarose gel electrophoresis. The
      detected incision activity was AP sites-dependent and EDTA-sensitive. The unit of
      enzymatic activity was defined as that amount able to incise 1 ng of plasmid DNA
      carrying 1 AP site/plasmid at 30 degrees C in 10 min. The assay was used to
      measure the APE activity in 10 healthy individuals ages 25-48 years. Values
      ranged from 0.38 to 0.94 units/ng protein, with a mean value of 0.62. The use of
      the assay for screening of people with DNA base excision repair (BER) defects is
      proposed.

PMID- 9586768
TI  - F344/Shi rats bearing type b catalase-1 locus are sensitive to sodium L-ascorbate
      promotion of two-stage urinary bladder carcinogenesis.
AB  - Our previous data showed that F344/DuCrj and LEW/Crj rat strains bearing the type
      a catalase-1 locus (CS1a) are sensitive to the promoting activity of sodium L
      ascorbate (Na-AsA) in 2-stage urinary bladder carcinogenesis, whereas ODS/Shi and
      WS/ Shi rat strains bearing the type b catalase-1 locus (CS1b) are resistant. In
      present study, we investigated the susceptibility of F344/Shi rats also bearing
      the CS1 to the Na-AsA-promoting effects on bladder tumor development. Male rats,
      6 weeks old, were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in
      their drinking water for 4 weeks, then fed either basal diet supplemented with 5%
      Na-AsA or no chemicals for 32 weeks. The rats given BBN alone had a few small
      carcinomas in the urinary bladder. In contrast, animals administered BBN-Na-AsA
      had many large carcinomas. Administration of Na-AsA was associated with
      significant elevation of urinary pH and L-ascorbic acid. The results indicate
      that F344/Shi rats are sensitive to the promoting effects of Na-AsA on 2-stage
      urinary bladder carcinogenesis, and thus that the CS1 locus may not influence
      susceptibility to promotion.

PMID- 9586769
TI  - DNA adduct formation in human and rat mammary epithelium by N-hydroxy derivatives
      of 2-aminofluorene and 4-aminobiphenyl.
AB  - Primary cultures of rat mammary epithelium and the human mammary cell line MCF-12
      were incubated with 10 microM N-formyl-, N-acetyl-, or N-propionyl-derivatives of
      N-hydroxy-2-aminofluorene (N-OH-AF) or N-formyl-, or N-acetyl derivatives of N
      hydroxy-4-aminobiphenyl (N-OH-ABP), in the medium with or without 100 microM
      paraoxon, for 3 h. Carcinogen-DNA adducts in the nuclei were detected with an
      immunohistochemical method using polyclonal antibodies against N-(deoxyguano-8
      yl)-2-aminofluorene and ABP-DNA adducts. The relative amounts of adducts per
      nucleus were determined by image analysis. After treatment, more than 90% of the
      cells that were attached on the coverslip were alive, as determined by the trypan
      blue exclusion. All carcinogens produced adducts in both human and rat cells.
      Adduct formation by the formyl, but not the acetyl or porpionyl, derivatives was
      inhibited up to 65% by paraoxon. These results demonstrate that both acetyl and
      propionyl derivatives are primarily activated by cytosolic acetyltransferases and
      the formyl derivatives may be equally activated by the acetyltransferases and
      microsomal carboxylesterases. Additionally, the results suggest that exposure to
      aromatic amines may be a risk factor for human breast cancer.

PMID- 9586770
TI  - Analysis of the DNA damage induced by praziquantel in V-79 Chinese hamster
      fibroblasts and human blood cells using the single-cell gel electrophoresis
      assay.
AB  - The analysis of the genotoxicity of praziquantel, an effective antihelminthic
      widely used in countries where parasitic infections are still serious public
      health problems, has been extensively performed using diverse in vitro and in
      vivo assays and endpoints. However, results are not conclusive, since reports to
      date indicate either praziquantel is mutagenic, comutagenic, or even
      antimutagenic. In the present work, the clastogenic potential of praziquantel was
      investigated in V-79 Chinese hamster fibroblasts and human peripheral blood using
      a sensitive technique such as the single-cell electrophoresis assay. Results
      indicate that even though praziquantel induced DNA single-strand breaks both in V
      79 cells and unstimulated human leukocytes, this effect was not translated into
      persistent DNA damage, since neither SCE nor HPRT mutations were induced. This
      suggests that the effect observed in the SCGE assay is an early event not closely
      related to praziquantel mutagenicity, because this DNA damage could be
      efficiently repaired.

PMID- 9586771
TI  - Autism in tuberous sclerosis complex.
AB  - The frequency and clinical presentation of autism in 28 probands with tuberous
      sclerosis complex (TSC) are reported and risk factors that may influence the
      development of autism in TSC are examined. Eight probands meet ICD-10 and DSM-IV
      criteria for autism, an additional 4 meet criteria for pervasive developmental
      disorder (PDD). Twelve TSC probands with autism/PDD are compared to 16 TSC
      probands without these conditions for factors which may underlie the association
      of autism and TSC. A specific seizure type, infantile spasms, as well as mental
      retardation, are increased in the TSC, autistic/PDD group. Furthermore, rates of
      social phobia and substance abuse are elevated among first-degree relatives of
      TSC probands with autism compared to first-degree relatives of TSC probands
      without autism. Implications of these findings in understanding the association
      of autism and TSC are discussed.

PMID- 9586772
TI  - No difference in hippocampus volume detected on magnetic resonance imaging in
      autistic individuals.
AB  - Neuropathological and animal studies have implicated the hippocampus as having a
      potential role in autism. Current imaging methods are well suited to the detailed
      measurement of the volume of the hippocampus, which has received little attention
      in previous imaging studies in autism. We report the results of a magnetic
      resonance imaging (MRI) study of 35 autistic and 36 control subjects. Detailed
      (1.5 mm) MRI did not reveal differences in the volume of the hippocampus in
      autistic individuals.

PMID- 9586773
TI  - Depression in children with autism/pervasive developmental disorders: a case
      control family history study.
AB  - Limited information is available about the occurrence of depression in children
      with autism and other pervasive developmental disorders (PDD). Although
      depression has been described in autistic children, questions about its validity
      have often been raised. One approach to address this issue is to investigate
      family histories of those autistic children diagnosed with clinical depression.
      Based on data available in nonautistic children, autistic children with
      depression would be expected to show an increased family history of depression.
      Since studies of this nature have not been attempted in autistic children, we
      compared the family history of 13 autistic/PDD children with depression (11 male;
      2 female; M full-scale IQ 86.2, SD 24.2; M age 10.4 years, SD 2.2) with 10
      autistic/PDD children without a history of current or previous depression (9
      male; 1 female; M full-scale IQ 67, SD 12.9; M age 10.5 years, SD 1.6). Diagnosis
      of depression was based on the DSM-III-R criteria and confirmed independently by
      two psychiatrists. Ten (77%) of the depressed children had a positive family
      history of depression compared to 3 (30%) of the nondepressed group, t(21)=-2.4;
      p=.02. These findings lend support to the validity of depression as a distinct
      condition in some children with autism/PDD and suggest that, as in the normal
      population, autistic children who suffer from depression are more likely to have
      a family history of depression.

PMID- 9586774
TI  - Hello and goodbye: a study of social engagement in autism.
AB  - We videotaped 24 children, adolescents, and young adults with autism,
      individually matched for chronological age and verbal mental age with 24
      nonautistic persons with mental retardation, for their spontaneous and prompted
      greetings and farewells towards an unfamiliar adult. Compared with control
      subjects, those with autism were less likely to offer spontaneous verbal and
      nonverbal gestures of greeting and farewell, and were less likely to establish
      eye contact even when they were offered a greeting. There were also fewer
      autistic subjects who smiled, or who waved goodbye. Results corresponded with
      raters' subjective judgments of participants' interpersonal engagement with the
      stranger. One interpretation of the findings is that they reflect a relative lack
      of intersubjective engagement by autistic individuals.

PMID- 9586775
TI  - The responses of autistic children to the distress of others.
AB  - The behavior of preschool children from five groups (developmental language
      disordered, high-functioning autistic, low-functioning autistic, mentally
      retarded, and normally developing) were coded in three situations: presentation
      of a nonsocial orienting stimulus (an unfamiliar noise) and two social situations
      involving simulated distress on the part of an adult with whom they were playing.
      Cognitive level was correlated with level of responsiveness to stimuli only for
      the two retarded groups (mentally retarded and low-functioning autistic). Girls
      showed more prosocial behavior than boys in both social situations, independent
      of diagnosis. The language-disordered children showed only mild and subtle social
      deficits. The low-functioning autistic children showed pronounced deficits in
      responding in all situations. The mentally retarded and high-functioning autistic
      children showed good awareness of all situations, but were moderately impaired in
      their ability to respond prosocially; they rarely initiated prosocial behavior,
      but did respond to specific prompts. The behavioral feature that marked both
      autistic groups, in contrast to all other groups, was a lack of social
      referencing; they did not tend to look toward an adult in the presence of an
      ambiguous and unfamiliar stimulus. Results are discussed in terms of variability
      between and among high- and low-functioning autistic children, and implications
      for the core deficits in autism.

PMID- 9586776
TI  - The Autism Diagnostic Interview-Revised and the Childhood Autism Rating Scale:
      differences between diagnostic systems and comparison between genders.
AB  - Diagnoses for autism based on the Autism Diagnostic Interview-Revised (ADI-R) and
      the Childhood Autism Rating Scale (CARS) were examined for 83 individuals with
      suspected autism. Agreement between systems reached 85.7%. Participants receiving
      diagnosis of autism based on only one system were significantly younger in age
      than individuals receiving diagnoses according to both systems. Individuals who
      did not receive diagnosis of autism on the ADI-R had lower chronological and
      mental ages and lower CARS scores compared to individuals who received diagnosis
      of autism based on the ADI-R. Eighteen females and 18 males were matched to
      examine possible gender differences. No significant findings were revealed,
      suggesting that the symptoms of autism according to the ADI-R and CARS do not
      differ between males and females when matched for chronological and mental ages.

PMID- 9586777
TI  - Evaluation of a mechanical hand-support for facilitated communication.
AB  - A specially designed hand-support device was evaluated to determine its
      effectiveness in assisting nonspeaking mentally handicapped children transition
      from facilitated communication (FC) to independent typing. Six autistic
      individuals (age range: 5 to 31) participated in the main experiment. All six had
      been reported to be moderately to highly proficient in the use of FC prior to the
      study. Pre- and posttraining tasks included pointing to pictures, numbers, and
      letters as well as copying single words by typing on a keyboard or letterboard.
      After 8 weeks of training, subjects' ability to point or type on all four tasks
      was assessed in three different conditions: (a) with an experienced facilitator,
      (b) independently, and (c) with the mechanical hand-support system.
      Postassessment measures did not reveal any evidence of independent communication
      with or without the device. An informal extension of the study, in which four of
      the original six subjects and three additional subjects were included for 4
      additional months, also failed to provide evidence of significant communication.

PMID- 9586778
TI  - Reducing disruptive behavior of a group-home resident with autism and mental
      retardation.
AB  - A treatment package consisting of a DRO procedure, token fines, and prompted
      relaxation was used to reduce the agitated-disruptive behavior of a person with
      autism and mental retardation living in a community group home. The agitated
      disruptive behaviors (cursing, hitting, kicking, throwing objects, and verbal
      threats) were measured during three different activities in a group home. The
      baseline rates of the agitated-disruptive behavior during one of these activities
      was relatively low, during another was moderate, and during the third was high.
      DRO procedures were partially implemented by a peer with Down syndrome and mental
      retardation during a portion of the study. Effects of the DRO procedures were as
      follows: During each activity an initial reduction of agitated-disruptive
      behavior was dependent on choosing an appropriate DRO interval, with shorter DRO
      intervals required during activities in which the baseline rates of the agitated
      disruptive behavior were higher. Once shorter DRO intervals had been used to
      reduce agitated-disruptive behavior, longer DRO intervals were effective in
      maintaining those reductions. Reductions were maintained for up to 6 months.

PMID- 9586779
TI  - Response to Howlin on the value of auditory integration training.

PMID- 9586780
TI  - Are there other disorders or disabilities associated with autism?

PMID- 9586782
TI  - Comparative stereochemical analysis of glucose-binding proteins for rational
      design of glucose-specific agents.
AB  - There is a need for synthesizing glucose-sensitive molecules which can be used in
      glucose sensors and self-regulating insulin delivery devices. Currently, glucose
      sensitive proteins, such as glucose oxidase and concanavalin A (Con-A), are used
      for detecting glucose molecules. For long-term in vivo applications, it is
      necessary to synthesize non-proteineous glucose-sensitive molecules which are
      biocompatible, nontoxic, cost-effective, and independent of environmental factors
      such as pH, ionic strength, or the presence of divalent cations. As a first step
      toward synthesizing glucose sensitive molecules, we have compared glucose-binding
      sites of four different types of glucose-binding proteins. They are human beta
      cell glucokinase, D-xylose isomerase, lectins (Lathyrus ochrus isolectin I and
      Con-A), and glucose/galactose binding protein. Analysis of the glucose-binding
      sites of their 3-dimensional crystal structures showed that the hydrogen bonds
      between the hydroxyl groups of glucose and a few types of amino acid residues of
      proteins provided the main attraction. In some cases, the same atom was involved
      in multiple hydrogen bonds. Hydrophobic interactions between the pyranose ring of
      glucose and aromatic rings of hydrophobic amino acid residues also played an
      important role in the glucose specificity. A sandwich geometry was observed among
      the hydrophobic groups. This comparative stereochemical analysis suggests that a
      possible glucose binding site can be made by placing Asp and Asn around glucose
      for hydrogen bonding and Phe on both sides of glucose for hydrophobic
      interaction.

PMID- 9586783
TI  - Ultrathin films of charged polysaccharides assembled alternately with linear
      polyions.
AB  - As a means of preparation of biocompatible molecular surfaces, an alternate
      assembly of charged polysaccharides and oppositely-charged synthetic polymers was
      conducted. Cationic chitosan was assembled alternately with anionic poly(sodium
      styrenesulfonate) (PSS) at pH 4. Regular film growth and its dependence on ionic
      strength were detected by the quartz crystal microbalance (QCM) method. Averaged
      film thicknesses for the chitosan + PSS layer were 15, 31, 46, and 69 A,
      respectively, when 0, 0.25, 0.5, and 1 M of NaCl was contained in aqueous
      chitosan. Adsorption of chitosan did not reach saturation in 20 min at 0 M NaCl,
      while the adsorption became saturated within 6 min with 0.25 M NaCl. Anionic
      sodium chondroitin sulfate was also assembled in alternation with cationic
      poly(dimethyldiallylammonium chloride) (PDDA) at pH 6.5. The adsorption of
      chondroitin sulfate was less sensitive to ionic strength. Surface morphology of
      chitosan-PSS films was investigated by non-contact atomic force microscopy (AFM)
      observation. Maximum height difference and Ra value for a 1000 x 1000 nm area
      were 11 and 0.69 nm, respectively, indicating the formation of a molecularly flat
      surface by alternate layer-by-layer adsorption.

PMID- 9586781
TI  - Regulation of intracellular metabolism by biodegradable polyrotaxanes.
AB  - Cellular response to our designed biodegradable polyrotaxanes was investigated in
      terms of changes in cytoplasmic calcium levels in platelets. The polyrotaxanes
      regulated thrombin-induced calcium increase in platelets although constituent
      molecules of the polyrotaxanes showed fewer effects on the intracellular
      metabolism. Further, an increase in membrane fluidity of red blood cell ghosts
      was significantly observed by the addition of the polyrotaxanes. Static light
      scattering study revealed that the polyrotaxanes formed a supramolecular
      association state in relation to the molecular weight of PEG: a loosely packed
      association with a specific molecular shape. From these characteristics, it is
      suggested that supramolecular level interactions between the polyrotaxanes and
      cell membranes regulate the intracellular metabolism. It is concluded that these
      biodegradable polyrotaxanes can be feasible as temporarily-controlled
      bioactivator.

PMID- 9586784
TI  - Preparation of heparin-like surfaces by introducing sulfate and carboxylate
      groups on poly(ethylene) using an argon plasma treatment.
AB  - Carboxylate and sulfate groups were introduced at the surface of poly(ethylene)
      (PE) samples. This was accomplished by coating and immobilizing sodium 10
      undecenoate (C11(:)) and 10-undecene sulfate (S11(:)) on the polymer by means of
      an argon plasma treatment. The composition of the coated surfactant layer was
      proportional to the composition of the coating solution. The thickness of the
      surfactant layer on the surface of PE samples, which were precoated from an
      aqueous solution with a total surfactant concentration of 0.30 M, was about 55 A.
      The presence of carboxylate and sulfate groups after plasma treatment of the
      precoated surfaces was confirmed by X-ray photoelectron spectroscopy (XPS). About
      20% of the initial amount of functional groups of the coated surfactants was
      retained at the PE surface. The ratio of carboxylate/sulfate groups at the plasma
      treated surfaces was dependent on the composition of the precoated surfaces. The
      minimum surface density of these groups on the resulting samples was about one
      group per 40 A2.

PMID- 9586786
TI  - Immobilization of alpha-chymotrypsin on oxygen-RF-plasma functionalized PET and
      PP surfaces.
AB  - In this contribution the immobilization of alpha-chymotrypsin on plasma activated
      PET and PP surfaces is investigated. The 'anchoring' C=O groups on polymer
      surfaces were created under RF-O2-plasma environments. The identity and relative
      concentrations of plasma-created functionalities were evaluated using survey and
      high resolution X-ray photoelectron spectroscopy, and differential attenuated
      total reflectance-FTIR spectroscopy. Surface morphology changes of plasma-exposed
      substrates were analyzed by atomic force microscopy. Enzyme assays were performed
      from both virgin and plasma modified samples which underwent the immobilization
      procedure. It was demonstrated that cold-plasma technique is suitable for
      generating functional, synthetic polymeric surfaces which can initiate enzyme
      coupling reactions. It also has been shown that the activity of the immobilized
      enzyme is lower in comparison to the free enzyme. Reduced conformational mobility
      resulting from multiple-point coupling process might be responsible for this
      behavior.

PMID- 9586785
TI  - Comparative anticoagulant activity and influence on thrombin generation of
      dextran derivatives and of a fucoidan fraction.
AB  - CMDBS compounds are synthetic dextran derivatives with a random distribution of
      glucosyl units substituted with carboxymethyl, benzylamide, sulfonate, and
      sulfate groups. Fucoidans are sulfated polysaccharides extracted from brown
      seaweeds. CMDBS and fucoidans exhibit anticoagulant activity which depends on
      their chemical composition and molecular weight. Tested with purified proteins,
      these compounds catalyse thrombin (EC 3.4.21.5) inhibition mainly via heparin
      cofactor II (HCII). We investigated the mechanism involved in the anticoagulant
      activity of these polysaccharides relative to that of heparin. Three CMDBS with
      different chemical compositions were studied to evaluate the effect of sulfate
      and sulfonate groups on the anticoagulant activity. The fucoidan fraction was
      extracted from the brown seaweed Ascophylum nodosum. The clotting assays
      (activated partial thromboplastin time, thrombin time, prothrombin time) were
      significantly prolonged in the presence of CMDBS and fucoidan, which were less
      active than heparin. To investigate the action mechanism of these
      polysaccharides, thrombin generation tests (TGT) were performed on human plasma
      in the presence of several CMDBS and a fucoidan fraction. The results showed an
      inhibition of thrombin generation in contact-activated plasma in the presence of
      both polysaccharides, with a prolonged lag phase preceding the burst of thrombin
      generation. In thromboplastin-activated plasma, thrombin generation was inhibited
      by CMDBS and fucoidan, with a prolonged lag phase only in the presence of CMDBS.
      The data obtained with each polysaccharide, compared to those obtained with
      heparin (our study) and hirudin (published data), led to hypothesize that
      fucoidan could act, like heparin, by forming complexes with the inhibitor
      (although antithrombin (AT) in the case of heparin, and HCII for fucoidan), while
      CMDBS could act, like hirudin, by forming complexes with thrombin.

PMID- 9586787
TI  - The anabolic effects of IGF-1 in skeletal muscle after burn injury are not caused
      by increased cell volume.
AB  - BACKGROUND: In a recent report, insulin-like growth factor 1 (IGF-1) stimulated
      protein synthesis and inhibited protein breakdown in skeletal muscle after bum
      injury. The mechanism of the anabolic effects of IGF-1 in skeletal muscle is not
      known. We tested the hypotheses that IGF-1 stimulates protein synthesis and
      inhibits protein breakdown in skeletal muscle secondary to cell swelling and that
      cell swelling in itself induces an anabolic response in muscle tissue. METHODS:
      Extensor digitorum longus muscles from control and burned rats were incubated in
      the absence or presence of 1 microg/mL of IGF-1. Protein synthesis and breakdown
      rates were determined by measuring incorporation of 14C-phenylalanine into
      protein and net release of tyrosine, respectively. Cell volume was measured by
      determining wet and dry weight and by using 3H-mannitol as an extracellular
      marker. RESULTS: IGF-1 stimulated protein synthesis and inhibited protein
      breakdown in muscles from nonburned and burned rats without influencing cell
      volume. Incubating muscles in hypo-osmotic medium increased cell volume by 17%
      and inhibited protein breakdown by 14% but did not influence protein synthesis.
      CONCLUSIONS: The anabolic effects of IGF-1 in skeletal muscle are not caused by
      increased cell volume. The results differ from those reported previously in liver
      cells in which the anabolic effects of IGF-1 were associated with cell swelling.
      The role of changes in cell volume in the regulation of protein metabolism may be
      different in skeletal muscle than in other tissues.

PMID- 9586788
TI  - Comparison of total parenteral nutrition and an oral, semielemental diet on body
      composition, physical function, and nutrition-related costs in patients with
      malabsorption due to acquired immunodeficiency syndrome.
AB  - BACKGROUND: The nutrition management of patients with malabsorption syndromes due
      to acquired immunodeficiency syndrome (AIDS) is problematic. The aim of this
      study was to compare the effects of total parenteral nutrition (TPN) and an oral,
      semielemental diet (SED) on body weight, body composition, quality of life,
      survival, and medical costs in AIDS patients with malabsorption. METHODS: This
      was a prospective, randomized, open-label study performed in outpatients. Twenty
      three AIDS subjects (TPN group, 12; SED group, 11) with cryptosporidiosis,
      microsporidiosis, or malabsorption of unknown cause were randomized and followed.
      Subjects were prescribed equivalent amounts of formulas of similar composition
      for 3 months. Monthly estimations of caloric intake, body weight, body
      composition by bioimpedance analysis, and quality of life were recorded.
      Nutritional variables were analyzed by repeated-measures analysis of covariance,
      with the baseline measure as the covariate. Nutrition-related medical costs,
      survival, and indices of absorptive and immune function were compared, RESULTS:
      Subjects had lost an average of 1.5 and 1.0 kg body wt/mo for TPN and SED during
      the 6 months before study entry (p < not significant). The TPN group consumed
      more total calories than the SED group (p < .05). Weight change during therapy
      was significantly different from pretreatment in both groups (p < .01 for TPN, p
      = .023 for SED). The TPN group gained more weight than the SED group (p = .057)
      and significantly more fat (p = .02), but the changes in body cell mass were
      similar in the two groups. Changes in weight and body composition correlated with
      caloric intake but not the mode of feeding. The SED group scored significantly
      better than the TPN group on a physical functioning subscale of quality of life
      (p < .01). Survival was similar in the two groups. TPN therapy cost almost four
      times more than SED. Peripheral blood CD4+ lymphocyte numbers were unaffected by
      either therapy. Intestinal function was not affected by either therapy.
      CONCLUSIONS: An oral SED may reverse weight loss and wasting in AIDS patients
      with malabsorption.

PMID- 9586789
TI  - Effects of insulin-like growth factor 1 on neutrophil and monocyte functions in
      normal and septic states.
AB  - BACKGROUND: Insulin-like growth factor 1 (IGF-1) mediates anabolic actions in
      catabolic states and also influences the immune system. Endogenous IGF-1
      production is suppressed in sepsis; replacement therapy is therefore a natural
      approach to obtain the protein anabolic and potentially immune-stimulating
      effects of IGF-1. METHODS: Twenty-two piglets were randomized to three groups: an
      IGF-1 group (n = 8) receiving a continuous infusion of 1.3 mg/h of IGF-1, a
      nontreated septic control group (n = 8), and a nonseptic control group (n = 6)
      receiving saline. Phagocytosis and respiratory burst in porcine neutrophils were
      evaluated by flow cytometry (FCM); tumor necrosis factor (TNF) levels were
      measured in serum during the septic period. In addition, human neutrophils and
      monocytes were primed in vitro with IGF-1 and subsequently were stimulated with
      phorbol myristate acetate (PMA) or Escherichia coli; phagocytosis and respiratory
      burst were evaluated by FCM. RESULTS: Under nonseptic conditions, pretreatment
      with IGF-1 suppressed the ability of neutrophils to ingest bacteria (ie, the
      level of phagocytosis) 43.4% +/- 2.7% (IGF-1-treated) vs 55.8% +/- 3.4%
      (nontreated septic controls) and 57.3% +/- 3.34% (nonseptic controls) (p = .01).
      When challenged by live E. coli infusion, phagocytosis increased in the IGF-1
      group to the levels of the nontreated group. The respiratory burst showed a
      convincing priming effect of IGF-1. After 4 hours of sepsis, the mean
      fluorescence intensity was 63.1 +/- 6.9 in the IGF-1 group and 40.7 +/- 3.0 in
      nontreated septic controls. The serum levels of TNF-alpha in the nontreated
      septic control group were twice those in the IGF-1-treated group, ie, 65.7 +/-
      13.1 pg/mL in the nontreated septic controls and 31.5 +/- 7.5 pg/mL in the IGF-1
      group (p = .03). In vitro priming of human neutrophils and monocytes with IGF-1
      and subsequent stimulation with PMA or E. coli demonstrated that IGF-1 enhanced
      both phagocytosis and respiratory burst. CONCLUSIONS: IGF-1 serves as a priming
      agent for biologic functions of leukocytes.

PMID- 9586790
TI  - Fecal short-chain fatty acids predict digestive disorders in premature infants.
AB  - BACKGROUND: Excretion of fecal short-chain volatile fatty acids (SCFAs) may
      indicate changes in colonic or colonocyte metabolism. The aim of this study was
      to detect the existence of an average fecal SCFA profile and to define which
      changes were associated with clinical events that occurred during the survey
      period. METHODS: SCFA profiles of 185 stool samples collected from 46 fed preterm
      neonates (mean birth weight, 1920 g; mean gestational age, 32.8 weeks) were
      evaluated and their association with digestive disorders or therapy was explored.
      RESULTS: Total SCFA concentration increased from 0 to 80 micromol/g feces wet
      weight over the first 20 days of life. A basic SCFA profile revealed the
      existence of a highly sensitive period between the second and the third week of
      life. In the absence of any digestive problem (n = 15), the butyric acid (C4)
      ratio increased from 7% to 24%. Phototherapy (n = 13) enhanced the SCFA
      concentration but decreased the ratios of C4 and minor acids. Digestive disorders
      reported included abdominal distention (n = 6) or bleeding (n = 8). Only in the
      case of bleeding was the SCFA profile changed by an enhancement of C4 by >50%.
      Antibiotic therapy (n = 3) suppressed SCFA production. CONCLUSIONS: This study
      supports a hypothesis that changes in the SCFA profile could offer a noninvasive
      method to anticipate functional modifications of the gastrointestinal tract
      before the first clinical signs of pathologic events, including necrotizing
      enterocolitis.

PMID- 9586792
TI  - A valid and reliable tool to quantify stool output in tube-fed patients.
AB  - A major problem in determining whether diarrhea exists in tube-fed patients is
      the quantification of stool output. On the basis of this need a stool output
      assessment tool was developed and tested for validity and reliability. Interrater
      reliability and construct validity were determined by using staff nurses' and
      principal investigators' observations. Observers blindly rated the bowel movement
      (BM) on size and consistency and on whether the BM was thought to represent
      "diarrhea." Interrater reliability was found to be significant. Stool output
      scores were determined by using a 24-hour output form that assessed stool size,
      consistency, and frequency. Content validity was established as well as
      concurrent and construct validity.

PMID- 9586791
TI  - Inorganic phosphorus reduces hypercalciuria during total parenteral nutrition by
      enhancing renal tubular calcium absorption.
AB  - BACKGROUND: Increasing the inorganic phosphorus content of total parenteral
      nutrition (TPN) formulas has been shown to decrease TPN-induced hypercalciuria in
      experimental animals and humans. The mechanism of this effect, however, has been
      uncertain. METHODS: By using a randomized cross-over design, seven patients on
      cyclic TPN were given otherwise identical formulas providing either 15 or 45
      mmol/d of inorganic phosphorus. Urinary calcium excretion, serum ultrafilterable
      calcium, filtered calcium load, fractional calcium excretion, urinary cyclic
      adenosine 5'-monophosphate (cAMP), and serum levels of ionized calcium,
      parathyroid hormone (PTH), and vitamin D metabolites were determined at the end
      of each study period. RESULTS: Urinary calcium excretion was significantly lower
      when the patients received the higher inorganic phosphorus formula. Increasing
      the inorganic phosphorus in the TPN formula did not change ultrafilterable
      calcium or filtered calcium load, but significantly reduced fractional calcium
      excretion. No differences in serum levels of ionized calcium, PTH, 25
      hydroxyvitamin D, 1,25-dihydroxyvitamin D, or urinary cAMP were observed between
      treatments. CONCLUSIONS: These results demonstrate that increasing the inorganic
      phosphorus content of the TPN formula decreases urinary calcium excretion by
      increasing renal tubular calcium resorption. This effect is not due to
      alterations in the PTH-1,25-dihydroxyvitamin D axis, but likely reflects a direct
      action of inorganic phosphorus on the renal tubules.

PMID- 9586793
TI  - Arginine, fish oil, and donor-specific transfusions independently improve cardiac
      allograft survival in rats given subtherapeutic doses of cyclosporin.
AB  - BACKGROUND: Dietary supplementation with a fish oil and arginine-enriched
      immunoenhancing diet (Impact; Sandoz Nutrition, Minneapolis, MN) in a rat cardiac
      allograft model using donor-specific transfusion (DST) and cyclosporin (CsA)
      resulted in significant prolongation of cardiac allograft survival with many
      animals developing long-term tolerance. This study was done to determine whether
      arginine or fish oil was the active ingredient. METHODS: A standard AIN-76A diet
      was modified to include either 10% fish oil, 2% arginine, or 5% arginine with or
      without fish oil. Diets were fed to Lewis strain rats that received Ax C9935
      Irish (ACI) heterotopic cardiac allografts beginning on day 1 and continuing
      indefinitely. A DST (1.0 mL ACI whole blood) was given with 10 mg/kg CsA on day 1
      relative to transplant and 2.5 mg/kg/d on days 0 to 6. Groups of animals
      receiving AIN-76A diet fortified with 2% glycine and animals receiving a DST or
      DST/CsA and regular laboratory chow served as controls. RESULTS: Mean survival
      times +/- SEM in days were as follows: untreated, 7.1 +/- 0.4; CsA/2% glycine,
      8.5 +/- 0.6; DST only, 9.6 +/- 1.1; DST/CsA, 26.6 +/- 6.4; CsA/2% arginine, 25.5
      +/- 3.9; DST/CsA/2% arginine, 68.7 +/- 8.9; DST/CsA/5% arginine, 90.1 +/- 31.1;
      CsA/fish oil, 73.6 +/- 26.1; and DST/CsA/fish oil/5% arginine, 90.1 +/- 31.1. The
      effect of arginine was slightly dose dependent and was seen best in combination
      with DST, but the effect of fish oil was not enhanced by DST. CONCLUSIONS: Both
      fish oil and arginine dietary supplementation significantly improved allograft
      survival but through different mechanisms (DST vs non-DST dependent).

PMID- 9586794
TI  - The role of cytokines in the catabolic consequences of infection and injury.
AB  - During infection and injury a series of metabolic events are activated that leads
      to a state of negative nitrogen balance and significant loss of lean body mass.
      This process is characterized by marked anorexia, net whole body protein
      breakdown, and liver anabolism. This host response initially is beneficial to the
      body because it helps it to fight disease and enhance healing. However, if such
      imbalance is maintained for long periods, it will invariably produce significant
      loss of lean body mass that may lead to a series of untoward clinical events. The
      role of the proximate cytokines, tumor necrosis factor (TNF), interleukin-1 (IL
      1), and interleukin-6 (IL-6) as well as glucocorticoids as important mediators of
      many pathophysiological manifestations of infection and injury has been studied
      extensively. However, the involvement of other mediators, at least in skeletal
      muscle proteolysis during sepsis has been hypothesized, because blockade of
      glucocorticoids, TNF, IL-1, and IL-6 reduces but does not normalize protein
      breakdown rates nor does the direct application of these mediators to skeletal
      muscle in vitro enhance proteolysis. Furthermore other studies have suggested
      that the lymphokine, interferon-gamma (IFN-gamma, type II interferon or immune
      interferon), produces fever and enhances thermogenesis, body weight loss, and
      skeletal muscle depletion in rodents in a manner similar to that seen with TNF
      and IL-1. Cytokines appear to be major components of the host metabolic response
      during infection and injury. However, neither all the cytokines involved nor the
      exact mechanisms underlying their metabolic effects are completely understood.
      The regulation of muscle protein synthesis and breakdown, which largely
      determines the development of cachexia, appears to depend on the delicate balance
      between a number of regulatory substances including cytokines, glucocorticoids,
      catecholamines, insulin, and insulin-like growth factors.

PMID- 9586795
TI  - Grains or veins: is enteral nutrition really better than parenteral nutrition? A
      look at the evidence.
AB  - BACKGROUND: Enteral nutrition is said to be better than parenteral nutrition for
      providing nutrition support to humans. PURPOSE: To assess the literature
      documenting the assertions that enteral nutrition is superior to parenteral
      nutrition with respect to cost, safety, physiology, intestinal structure and
      function, bacterial translocation, and outcome. DATA IDENTIFICATION: Sources
      included MEDLINE search, personal files, and references from human comparative
      studies of enteral vs parenteral nutrition. STUDY SELECTION: The goal was to
      include all human studies directly addressing questions of comparative efficacy
      of enteral and parenteral nutrition. Emphasis was given to prospective randomized
      controlled studies where available. Retrospective comparisons were not included.
      DATA EXTRACTION: An attempt was made to briefly summarize methodology and
      findings of relevant studies. No general attempt was made to assess quality of
      individual studies. RESULTS OF DATA SYNTHESIS: Enteral nutrition appears to be
      less expensive than parenteral nutrition, but new economic analyses are needed
      given the newer aggressive access techniques for enteral nutrition. Enteral
      nutrition is associated with meaningful morbidity and mortality. The little
      comparative data existent suggest no differences in safety. Comparative studies
      of physiology and metabolism as well as comparative and noncomparative studies of
      intestinal function and structure do not support putative advantages of enteral
      nutrition. There is no evidence that enteral nutrition prevents bacterial
      translocation in humans. Enteral nutrition probably reduces septic morbidity
      compared with parenteral nutrition in abdominal trauma. Otherwise, there is no
      evidence that enteral nutrition consistently improves patient outcome compared
      with parenteral nutrition. CONCLUSIONS: With the exception of decreased cost and
      probable reduced septic morbidity in acute abdominal trauma, the available
      literature does not support the thesis that enteral nutrition is better than
      parenteral nutrition in humans.

PMID- 9586796
TI  - Glutamine protects intestinal epithelial cells: role of inducible HSP70.

PMID- 9586798
TI  - Glutathione in human plasma: decline in association with aging, age-related
      macular degeneration, and diabetes.
AB  - Blood samples were analyzed for GSH and GSH redox state in 40 age-related macular
      degeneration (ARMD) patients (> 60 y), 33 non-ARMD diabetic patients (> 60
      years), 27 similarly aged non-ARMD and nondiabetic individuals (> 60 years), and
      19 younger individuals (< 60 years) without ARMD or diabetes. Results showed a
      significantly lower plasma GSH in older individuals (ARMD, diabetes, and
      controls) than in younger individuals (p < .01). Total GSH (GSHt) obtained
      following treatment with dithiothreitol was significantly lower only in diabetic
      cases (p < .05) but also approached significance for ARMD cases (p = .089).
      Estimation of redox potential indicated that the plasma GSH pool is considerably
      more oxidized in all of the older groups. Analyses of whole blood GSH showed that
      GSH was significantly lower in diabetic cases compared to the other groups, but
      did not reveal any difference associated with age or ARMD. In contrast, GSSG in
      whole blood was significantly higher in the older groups compared to the younger
      controls. The results suggest that in studies of age-related pathologies,
      oxidation of GSH may be a more important parameter than a decline in pool size,
      while in specific pathologies such as diabetes, both oxidation and a decline in
      pool size may be important.

PMID- 9586797
TI  - The effects of serum iminodipeptides and prednisolone on superoxide generation
      and tyrosyl phosphorylation of proteins in neutrophils from a patient with
      prolidase deficiency.
AB  - The aim of this study was to examine the effects of serum iminodipeptides and
      prednisolone on superoxide generation and tyrosyl phosphorylation of proteins in
      neutrophils from a patient with prolidase deficiency, and also to find the
      causative effects of superoxide on inflammatory skin lesions. When the
      neutrophils from a patient with prolidase deficiency (PDPPMN) were preincubated
      with prolyl-proline (Pro-Pro), which is one of the iminodipeptides found at high
      concentration in the serum of patients with prolidase deficiency, the N-formyl
      methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation was enhanced
      in a concentration-dependent manner, although the extent of enhancing effect was
      lower than that in neutrophils from healthy humans (HPPMN). Pro-Pro also enhanced
      superoxide generation induced by opsonized zymosan (OZ) in PDPPMN but not that
      induced by arachidonic acid or phorbol 12-myristate 13-acetate. Herbimycin A and
      genistein decreased the fMLP- and OZ-induced superoxide generations after priming
      by Pro-Pro. 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine (H-7) and
      staurosporine did not decrease, but rather enhanced, the superoxide generation in
      a low concentration range. When PDPPMN were prepared, tyrosyl phosphorylation of
      45 kDa protein in PDPPMN had already occurred. The phosphorylation was scarcely
      increased by incubation of the cells with Pro-Pro, in contrast to that in HPPMN.
      Genistein decreased the phosphorylation of 45 kDa protein in both PDPPMN and
      HPPMN. These results suggest that the priming effect of iminodipeptides on
      superoxide generation in PDPPMN is coupled with phosphorylation of 45 kDa protein
      by protein tyrosine kinase. Protein tyrosine kinase may play a critical role(s)
      in the regulatory mechanism of priming by iminodipeptides and activation of NADPH
      oxidase in the patient's neutrophils. In prolidase deficiency, the characteristic
      skin manifestations are inflammatory indurations and chronic leg ulcers.
      Prednisolone improves the ulcers, and this compound decreased the fMLP- and OZ
      induced superoxide generation and tyrosyl phosphorylation of 45 kDa protein in
      the patient's neutrophils after priming by Pro-Pro. When inflammatory skin
      lesions were present, the levels of iminodipeptides in the patient's serum were
      elevated and the superoxide generation by neutrophils was up-regulated. When skin
      lesions were healing or absent, the levels of iminodipeptides in the patient's
      serum and superoxide generation by neutrophils were higher than those of healthy
      controls but lower than those in the inflammatory stages. Thus, the enhancement
      of superoxide generation by neutrophils via serum iminodipeptides would be one of
      the inducers of inflammatory skin lesions. Corticosteroid administration might be
      a therapeutic modality of choice for skin lesions.

PMID- 9586800
TI  - The use of the frog palate preparation to assess the effects of oxidants on
      ciliated epithelium.
AB  - This work was designed to develop a simple method based on the frog palate
      preparation to study the effects of hydrogen peroxide (H2O2) on ciliated
      epithelium. For this purpose, five sets (n = 10 per set) of frog palate
      preparations (Rana catesbeiana) were studied during 35 min after immersion in
      increasing concentrations of H2O2: 1, 8, 16, 32, and 64 microM. The effects of
      H2O2 on ciliated epithelium were assessed by measuring transepithelial potential
      difference (PD) and mucociliary transport (MT). Measurements were performed at 5
      min intervals. In addition, the palates submitted to the 64 microM dose were
      immersed in Ringer's solution and followed by another 30 min to assess the
      possible recovery after maximal injury. Transepithelial potential difference (PD)
      was measured by means of agar-filled microelectrodes connected to the high input
      of a grounded electrometer. Mucociliary transport (MT) was determined by directly
      monitoring the movement of autologous mucus along the palate surface. Significant
      decrease in MT was observed in 16 microM and beyond and significant change in PD
      was observed in 32 microM and 64 microM. Palates submitted to 64 microM of H2O2
      returned to their baseline levels of PD and MT within 30 min of recovery in
      Ringer's solution. In conclusion, the frog palate preparation was shown to be an
      efficient experimental tool to assess the deleterious effects of H2O2 on the
      ciliated epithelium.

PMID- 9586799
TI  - Nitric oxide donors protect cultured rat astrocytes from 1-methyl-4
      phenylpyridinium-induced toxicity.
AB  - MPP+ is thought to mediate MPTP's toxicity on dopamine neurons by inhibiting
      mitochondrial respiration. However, astrocytic injuries are also observed in
      MPTP/MPP+-treated rats. Because nitric oxide (NO.) is suggested to be
      cytoprotective, we examined the effects of nitroprusside (SNP), S-nitroso-N
      acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1) on MPP+-induced
      toxicity in astrocytes. Incubation of astrocytes with MPP+ for 2 days produced a
      dose-dependent toxicity, including increase in lactate level and lipid
      peroxidation, decrease of metabolic activity and cell damage. SNP, SNAP, and SIN
      1 all attenuated MPP+-induced toxicity. The same protection was not achieved with
      N-acetylpenicillamine or ferrocyanide, structural analogues of SNAP or SNP but
      devoid of NO.. Further, the effect was not attributed to the increased cGMP
      levels or blockade of MPP+ accumulation in astrocytes. Notably, catalase,
      dimethyl sulfoxide and ferricyanide, an extracellular electron acceptor, were
      also effective in inhibiting MPP+ damage. NO. donors and analogues were also
      tested against damage produced by rotenone, an irreversible complex I inhibitor.
      Only ferricyanide and SNP effectively protected rotenone's toxicity. These
      results concluded that (1) NO. may protect astrocytes from MPP+-induced free
      radical formation, and (2) prevention of energy depletion/free radicals
      production alleviate MPP+-induced toxicity.

PMID- 9586801
TI  - Comparison of oxidative base damage in mitochondrial and nuclear DNA.
AB  - The levels of endogenous pig liver cells mitochondrial DNA oxidative base damage
      have been investigated using isotope dilution gas chromatography mass
      spectrometry (GC/MS). Higher levels of five measured bases were found in mtDNA in
      relation to nuclear DNA. We have also detected large differences in the modified
      base ratios of mitochondrial versus nuclear DNA. These ratios for the bases with
      promutagenic properties as 8OHGua and 5OHCyt are much lower than for other bases
      (5OHHyd, 5OHMeHyd, 5OHMeUra).

PMID- 9586802
TI  - The lipid peroxidation inhibitor indenoindole H290/51 protects myocardium at risk
      of injury induced by ischemia-reperfusion.
AB  - Lipid peroxidation contributes to myocardial reperfusion injury. The indenoindole
      H290/51, a lipid peroxidation inhibitor with balanced lipophilicity and a
      considerably higher antioxidative capacity than that of vitamin E, was tested for
      its myocardioprotective effect against reperfusion injury. Coronary-ligated pigs
      were subjected to 45 min of myocardial ischemia followed by 240 min of
      reperfusion. Starting five minutes prior to reperfusion, H290/51 (n = 6) or
      vehicle (n = 6) was retrogradely infused via a coronary vein for 30 min. The
      total dose of H290/51 was 1 microM in 300 ml fluid (10 ml/min). In addition to
      the hemodynamics, left ventricular (LV) wall segment shortening (%SS) was
      measured by sonomicrometry. The LV area at risk and infarct size were measured by
      means of Evans blue and triphenyl tetrazolium chloride staining. The hemodynamics
      did not change significantly during the study, and no differences were found
      between the two groups. In the H 290/51-treated pigs, %SS of the ischemic area
      recovered from 1.9% at the end of ischemia to 9.1% after 120 min (p < .05) and to
      16.2% at 240 min (p < .01). There was no significant recovery in the vehicle
      group. The LV area at risk was approximately 20% of LV. Infarct size as a
      percentage of LV and of the area at risk was significantly smaller in the H290/51
      group (9+/-3% and 46+/-11%) than in the control group (18+/-6%; p < .05 and 83+/
      5%; p < .01). H290/51 effectively protected the myocardium at risk in the setting
      of myocardial ischemia followed by reperfusion. This effect was reflected by
      diminished infarct size and improved functional recovery.

PMID- 9586803
TI  - Evidence for accelerated generation of hydroxyl radicals in experimental
      obstructive jaundice of rats.
AB  - We present evidence herein of the accelerated generation of hydroxyl radical
      (.OH) in the plasma and the liver tissue of common bile duct ligated (CBDL) rats,
      a model for experimental obstructive jaundice. .OH production in the plasma was
      monitored in vivo by the identification of dihydroxybenzoates in plasma [2,3
      dihydroxybenzoate (2,3-DHB) and 2,5-dihydroxybenzoate (2,5-DHB)] using high
      performance liquid chromatography (HPLC). The average concentrations of 2,3-DHB
      and 2,5-DHB produced in the plasma of the controls were 33+/-3 microM and 232+/
      34 microM (n = 15), respectively, whereas their respective concentrations
      increased to 149+/-28 microM and 604+/-88 microM in the CBDL rats (n = 19).
      Furthermore, we also observed a time-dependent decreasing trend of 2,3-DHB and
      2,5-DHB production after surgical removal of the ligation of the experimental
      animals. In addition, the generation of .OH in the liver tissue was studied by
      using dimethyl sulfoxide (DMSO) as a molecular probe and measuring the amount of
      methanesulfinic acid (MSA), the product of the trapping reaction. The net
      production of MSA in the liver tissue of the control rats was 1.22+/-0.05 O.D.
      unit/g protein (n = 5), whereas its respective concentration of MSA in the liver
      tissue of CBDL rats increased to 2.05+/-0.15 O.D. unit/g protein (n = 5). In
      addition, we showed that CBDL rats receiving a pretreatment of mannitol, an .OH
      scavenger, resulted in the decreased production of MSA. Electron micrographic
      study indicated that the most prominent change observed in CBDL rats was the
      alteration of mitochondria, which were swollen with distorted cristae. Meanwhile,
      the bile canaliculi were moderately more dilated than that of the controls, and
      an increased neutrophil peripheral blood count was found in CBDL rats when
      compared to the controls. Taken together, our data suggest that accelerated
      generation of .OH in the CBDL rats is obvious and may play a key role in the
      pathogenesis of liver damage associated with obstructive jaundice.

PMID- 9586804
TI  - Azulenyl nitrones: colorimetric detection of oxyradical end products and
      neuroprotection in the gerbil transient forebrain ischemia/reperfusion model.
AB  - We present analytical and neuroprotective data on a unique spin trapping agent
      derived from a novel chemical class known as an azulenyl nitrone (AZN). Based on
      Colorimetric properties, AZN was used to assess the formation of free radicals in
      a bilateral carotid occlusion (BCO) model in gerbils by monitoring the conversion
      of the nitrone to the aldehyde in affected tissue. In addition, AZN was tested as
      a neuroprotectant in this model regarding the preservation of CA1 pyramidal cells
      of the hippocampus following transient ischemia/reperfusion. AZN was
      electrochemically oxidized to give the aldehyde using an HPLC system with on line
      electrochemical oxidation. The oxidation potential associated with a 50% loss of
      AZN occurred at about 600 mV (half-wave potential versus palladium electrode).
      The major product detected as AZN oxidation occurred in an aqueous methanolic
      medium was the corresponding azulenyl aldehyde. Oxidation of AZN was inversely
      related to the formation of the aldehyde. Based on this test, we considered the
      in vivo conversion of AZN to aldehyde to be a measurement of oxidative stress in
      tissue. Results show that 0.3% of hippocampal AZN was converted to aldehyde in
      animals treated as shams. However, in gerbils subjected to a 7-min ischemic
      insult plus 7-min reperfusion, the conversion rate was about 3 times higher at
      1.0%. In this model, surviving CA1 hippocampal neurons were counted from gerbils
      that were subjected to 7 mins of BCO followed by 5 days of reperfusion. In sham
      animals, about 89 cells were counted in a selected field of CA1 neurons. With
      injury, only 27 cells on average survived (70% loss) and were counted from this
      selected field. Under similar conditions and AZN treatment, 57 cells survived
      (36% loss). We conclude, therefore, that the demonstrated neuroprotection occurs
      because AZN neutralizes radicals which contribute to neuronal damage following
      ischemia/reperfusion.

PMID- 9586806
TI  - Photodynamically generated bovine serum albumin radicals: evidence for damage
      transfer and oxidation at cysteine and tryptophan residues.
AB  - Porphyrin-sensitized photoxidation of bovine serum albumin (BSA) results in
      oxidation of the protein at (at least) two different, specific sites: the Cys-34
      residue giving rise to a thiyl radical (RS.); and one or both of the tryptophan
      residues (Trp-134 and Trp-214) resulting in the formation of tertiary carbon
      centred radicals and disruption of the tryptophan ring system. In the case of
      porphyrins such as hematoporphyrin, which bind at specific sites on BSA, these
      species appear to arise via long-range transfer of damage within the protein
      structure, as the binding site is some distance from the ultimate site of radical
      formation. This transfer of damage is shown to depend on a number of factors
      including the conformation of the protein, the presence of blocking groups and
      pH. Alteration of the protein conformation results in radical formation at
      additional (or alternative) sites, as does blocking of the preferred loci of
      radical formation. The formation of these thiyl and tryptophan-derived radicals
      does not lead to significant aggregation or fragmentation of the protein, though
      it does result in a dramatic enhancement in the susceptibility of the oxidised
      protein to proteolytic degradation by a range of proteases. The generation of
      protein-derived radicals also results in an enhancement of photobleaching of the
      porphyrin, suggesting that protein radical generation is linked to porphyrin
      photooxidation.

PMID- 9586805
TI  - Redox-cycling of iron ions triggers calcium release from liver microsomes.
AB  - Elevation of cytosolic calcium levels has been shown to occur via oxidation of
      critical protein thiols in liver microsomes. Elevated cytosolic Ca2+ may also
      result from activation of calcium releasing channels. In the presence of NADPH or
      ascorbic acid, iron ions produced a concentration-dependent release of calcium
      from liver microsomes. Under anaerobic conditions, the iron-induced release of
      calcium was inhibited, suggesting that a reaction of oxidation triggers the
      releasing process. The calcium releasing process at pH 7.0 appears to be highly
      sensitive to activation by iron ions, as effective concentrations (e.g., 2-5
      microM) did not alter the Ca2+, Mg2+-ATPase or the phospholipid component of the
      microsomal membranes. Iron-induced Ca2+-release could occur under conditions in
      which there was no iron-induced microsomal lipid peroxidation. Under conditions
      of intense lipid peroxidation, PBN fully prevented the iron-induced accumulation
      of thiobarbituric reactive reagents without affecting the release of Ca2+,
      suggesting that lipid peroxidation is not the mechanism by which iron causes
      release of calcium. Trolox, GSH and high concentrations of ascorbate, however,
      strongly inhibited the iron-induced calcium release, most likely due to
      modulation of the Fe2+/Fe3+ ratio. While the IP3 receptor system is considered to
      be the main regulator of calcium release, liver also contains a ryanodine
      sensitive calcium releasing store. The iron-induced calcium release at pH 7.0 was
      blocked by ruthenium red, a specific inhibitor of the ryanodine receptor, and
      Fe2+ (but not Fe3+) decreased the binding of ryanodine, a specific ligand for the
      ryanodine-sensitive calcium channel. These results suggest that redox-cycling of
      iron ions results in an activation of a ryanodine-sensitive calcium channel.
      Activation of calcium releasing channels by iron may play a role in the evolution
      of various hepatic disorders that are associated with chronic iron overload in
      humans.

PMID- 9586807
TI  - Bioluminescence as a possible auxiliary oxygen detoxifying mechanism in elaterid
      larvae.
AB  - This work examines the hypothesis that beetle bioluminescent reactions may
      primarily have evolved to provide an auxiliary O2 detoxifying mechanism. The
      activities of antioxidant enzymes and of luciferase in the prothorax (bright) and
      abdomen (dim) of luminous larval Pyrearinus termitilluminans (Coleoptera:
      Elateridae) were measured after previous challenge with either hyperoxia,
      hypoxia, or the firefly luciferase inhibitor luciferin 6'-methyl ether (LME).
      Upon exposure to pure O2 for 72 h, the prothorax activities of total superoxide
      dismutase (SOD) and catalase were found to increase by 85% and 50%, respectively.
      Concomitantly, levels of luciferase and luciferin increased 80% and 50%. Assays
      of thiobarbituric acid reactive substances (TBARS) showed significantly augmented
      lipid peroxidation only in the abdomen (30%) where levels of antioxidant enzymes
      and especially luciferase are low. In contrast, exposure to hypoxia (2% O2) led
      to significant increases in prothorax citrate synthase (85%), succinate
      dehydrogenase (25%), and lactate dehydrogenase (30%) activities, but not in
      luciferase or antioxidant enzyme levels. LME administration alone decreased
      luciferase activities 20% but did not alter prothorax SOD activity. Prothorax SOD
      activity was increased by concomitant LME and hyperoxia treatments (30%), along
      with higher levels of TBARS (25%) and protein reactive carbonyl groups (50%).
      Altogether these data suggest that in elaterids, bioluminescence and reactions
      catalyzed by antioxidant enzymes may cooperate to minimize oxidative stress.

PMID- 9586808
TI  - Mechanisms of asbestos-induced nitric oxide production by rat alveolar
      macrophages in inhalation and in vitro models.
AB  - To evaluate the contribution of reactive nitrogen species to inflammation by
      asbestos, Fischer 344 rats were exposed to crocidolite or chrysotile asbestos by
      inhalation to determine whether increases occurred in nitric oxide (NO.)
      metabolites from alveolar macrophages (AMs). AMs from animals inhaling asbestos
      showed significant elevations (p < .05) in nitrite/nitrate levels which were
      ameliorated by NG-monomethyl-L-arginine (NMMA), an inhibitor of inducible nitric
      oxide synthase (iNOS) activity. Temporal patterns of NO. generation from AMs
      correlated with neutrophil influx in bronchoalveolar lavage samples after
      asbestos inhalation or bleomycin instillation, another model of pulmonary
      fibrosis. To determine the molecular mechanisms and specificity of iNOS promoter
      activation by asbestos, RAW 264.7 cells, a murine macrophage-like line, and AMs
      isolated from control rats were exposed to crocidolite asbestos in vitro. These
      cells showed increases in steady-state levels of iNOS mRNA in response to
      asbestos and more dramatic increases in both iNOS mRNA and immunoreactive protein
      after addition of lipopolysaccharide (LPS). After transfection of an iNOS
      promoter/luciferase reporter construct, RAW 264.7 cells exposed to LPS,
      crocidolite asbestos and its nonfibrous analog, riebeckite, revealed increases in
      luciferase activity whereas cristobalite silica had no effects. Studies suggest
      that NO. generation may be important in cell injury and inflammation by asbestos.

PMID- 9586809
TI  - Erythrocyte ascorbate recycling: antioxidant effects in blood.
AB  - Ascorbic acid is an important antioxidant in human plasma, but requires efficient
      recycling from its oxidized forms to avoid irreversible loss. Human erythrocytes
      prevented oxidation of ascorbate in autologous plasma, an effect that required
      recycling of ascorbate within the cells. Erythrocytes had a high capacity to take
      up dehydroascorbate, the two-electron oxidized product of ascorbate, and to
      reduce it to ascorbate. Uptake and conversion of dehydroascorbate to ascorbate
      was saturable, was half-maximal at 400 microM dehydroascorbate, and achieved a
      maximal intracellular ascorbate concentration of 1.5 mM. In the presence of 100
      microM dehydroascorbate, erythrocytes had the capacity to regenerate a 35 microM
      ascorbate concentration in blood every 3 min. Ascorbate recycling from DHA
      required intracellular GSH. Depletion of erythrocyte GSH by more than 50% with
      diamide did not acutely affect the cellular ascorbate content, but did impair the
      subsequent ability of GSH-depleted cells to recycle dehydroascorbate to
      ascorbate. Whereas erythrocyte ascorbate recycling was coupled to GSH, an
      overwhelming extracellular oxidant stress depleted both ascorbate and alpha
      tocopherol before the GSH content of cells fell appreciably. Recycled ascorbate
      was released from cells into plasma, but at a rate less than one tenth that of
      dehydroascorbate uptake and conversion to ascorbate. Nonetheless, ascorbate
      released from cells protected endogenous alpha-tocopherol in human LDL from
      oxidation by a water soluble free radical initiator. These results suggests that
      recycling of ascorbate in erythrocytes helps to maintain the antioxidant reserve
      of whole blood.

PMID- 9586810
TI  - Riboflavin-mediated axonal degeneration of postnatal retinal ganglion cells in
      vitro is related to the formation of free radicals.
AB  - It is well known that glial cells produce several neurotrophic factors. We
      detected a neurogedegenerative/neurite growth inhibiting activity in serum-free
      astrocyte-conditioned medium (ACM). After high performance liquid chromatography
      (HPLC)-purification, spectral analysis and test of biologic activity in tissue
      cultures of postnatal retinal explants we isolated a fraction containing a
      riboflavin-(vitamin B2)-like compound which caused the neuronal degeneration. We
      therefore investigated the influence of pure riboflavin on axonal regeneration in
      vitro. Riboflavin is a normal compound of Dulbecco's modified Eagle medium (DMEM)
      and other tissue culture media in various concentrations. The removal of
      riboflavin from ACM by reversed phase chromatography abolished the neurite growth
      inhibiting effect and enhanced the regenerative response of axonal outgrowth from
      postnatal rat retinal explants. However, doubling of the normal medium
      concentration (1 microM) of riboflavin lead to strong degenerative alteration of
      the outgrowing axons in a dose-dependent manner, even under maximal growth
      stimulation by cultivating the explants in astrocyte-conditioned medium. To check
      the possibility that riboflavin-mediated cytotoxicity is related to the
      production of free radicals through photoabsorption from daylight, we irradiated
      culture medium with UV light, and induced radical stress by incubating the
      explants with Fe2+/3+. In an other set of experiments, we proofed, if
      antioxidants/free radical scavengers like pyruvate or vitamin C and E are able to
      overcome the neurite growth inhibiting influence of riboflavin or the radical
      stress. Our findings suggest an involvement of riboflavin-mediated formation of
      free radicals/reactive oxygen species and subsequent neurite degeneration in in
      vitro-assays of neuronal regeneration or neuronal cell cultures. How far the
      riboflavin/free radical-induced axonal degeneration could be an explanation for
      neurological degenerative disorders has to be elucidated.

PMID- 9586811
TI  - Low catalase activity in xeroderma pigmentosum fibroblasts and SV40-transformed
      human cell lines is directly related to decreased intracellular levels of the
      cofactor, NADPH.
AB  - We have previously shown that fibroblasts from ultra-violet (UV) hypersensitive
      xeroderma pigmentosum patients (XP) are markedly deficient in catalase activity
      resulting in high intracellular levels of hydrogen peroxide (H2O2) following UV
      irradiation. No direct correlation between catalase activity and repair ability
      was found since XP variant cells which are proficient in nucleotide excision
      repair (NER) showed activities as low as those found in NER deficient classical
      XP groups A and D. However, in contrast to the skin cancer prone XP patients,
      another NER deficient syndrome, trichothiodystrophy (TTD), which does not exhibit
      any cancer predisposition, was found to present normal catalase activity.
      Moreover, it was found that a variety of SV40 transformed human cell lines also
      showed decreased catalase activities. Our previous data showed that a molecular
      analysis of the normal, XP, TTD or transformed human fibroblast cell lines did
      not reveal any differences in levels of catalase transcription or amount of
      catalase protein subunits. These results incited us to examine the
      structure/function relationship of the tetrameric active enzyme form of catalase
      (which is the only one able to carry out H2O2 dismutation) with its cofactor
      NADPH. In the present study, we have measured the effects on catalase activity
      after adding NADPH either to acellular extracts or during cell culture of the
      different cell types. The NADPH levels were also quantified directly in intact
      cells using flow cytometry. Our results show a clear relationship between low
      catalase activity and striking decrease in intracellular NADPH levels.

PMID- 9586812
TI  - Antioxidant enzyme response to hypericin in EMT6 mouse mammary carcinoma cells.
AB  - Antioxidant enzyme activities were measured following exposure to hypericin +/-
      irradiation in EMT6 cells. CuZnSOD and catalase activities peaked within 0.5 h
      following irradiation for nontoxic 0.5 microM hypericin and toxic 1.0 microM
      hypericin. Catalase remained elevated up to 3 h for 1.0 microM hypericin + light.
      MnSOD activity was elevated immediately following irradiation for both doses.
      These levels returned to control by 1 h for 0.5 microM hypericin, but were
      depressed after 1 h for 1.0 microM hypericin. This suggests that mitochondria
      impairment may be a critical factor in hypericin phototoxicity. Glutathione
      reductase was inhibited immediately following irradiation with 1.0 microM
      hypericin, suggesting that an altered status of the glutathione pool contributed
      to cytotoxicity. Glutathione peroxidase activities were elevated following
      irradiation but returned to control levels within 0.5 h for both doses,
      implicating hydroperoxide formation as an early event in hypericin phototoxicity.
      Inhibition by hypericin in the dark was demonstrated for purified CuZnSOD, Se
      dependent glutathione peroxidase, glutathione S-transferase, and glutathione
      reductase activities in vitro. Irradiation did not potentiate hypericin-mediated
      glutathione reductase inhibition and decrease inhibition for the other enzymes.
      Collectively, these data demonstrate an antioxidant enzyme response to hypericin
      photoactivation and confirm a role for oxygen in hypericin phototoxicity.

PMID- 9586814
TI  - The role of oxygen in cutaneous photodynamic therapy.
AB  - Photodynamic therapy (PDT) is based on the dye-sensitized photooxidation of
      biological matter in the target tissue, and utilizes light activated drugs for
      the treatment of a wide variety of malignancies. Skin is a target organ for PDT,
      because of the increasing incidence of skin cancers and the easy accessibility to
      photosensitizing drugs and light. Skin oxygen tension changes dramatically during
      and after PDT and seems to be an important treatment parameter. Experimental
      approaches to modulate oxygen tension (e.g., hyperbaric oxygenation,
      hyperthermia, or perfluorocarbons) have been studied mainly in animals, and some
      of these techniques may have the potential to be applied in humans to improve the
      efficacy and safety of PDT. The main purpose of this review is to provide the
      reader with current information on cutaneous oxygen physiology and oximetry, the
      role of oxygen and singlet oxygen (1O2) in PDT, and approaches to modulate skin
      oxygen tension. The literature indicates that it may be possible to utilize
      transcutaneous oxygen measurements as a valuable measure of the clinical
      effectiveness of PDT and as an in situ predictor of the energy required to elicit
      a biological response. Consequently the effectiveness of PDT can be manipulated
      by modulating skin oxygen tension.

PMID- 9586813
TI  - Receptor- and age-selective effects of dopamine oxidation on receptor-G protein
      interactions in the striatum.
AB  - The striatum contains a high concentration of oxidizable dopamine (DA), and the
      aged organism shows a decreased ability to respond to oxidative stress (OS),
      making this area extremely vulnerable to free radical insult. To determine the
      receptor specificity of this putative increase in OS sensitivity, striatal slices
      from 6- and 24-month-old animals were incubated (30 min, 37 degrees C) in a
      modified Krebs medium containing 0 to 500 microM DA with or without a
      preincubation (15 min) in a nitrone trapping agent, 1 or 5 mM alpha-phenyl-n-tert
      butyl nitrone (PBN), and changes in low Km GTPase activity (an index of receptor
      G protein coupling/uncoupling) assessed in muscarinic, 5-HT1A D1, and D2
      receptors stimulated with carbachol, 8 OH-DPAT-HBr, SKF 38393, or quinelorane,
      respectively. DA exposure induced selective decreases in the stimulated activity
      in all of these receptor systems, and an overall increase in conjugated dienes
      (56%) of the young. In the case of carbachol and 8 OH-DPAT-HBr, the DA-induced
      deficits in GTPase stimulation were seen primarily in the young (61 and 32%,
      respectively), while DA-induced deficits in quinelorane (D2) stimulation were
      seen in both age groups. In the case of SKF 38393-stimulation (D1) the DA-induced
      deficits were higher in the striatal tissue from the old. The DA-induced
      decreases in carbachol stimulated GTPase activity in the tissue from the young
      could be prevented by pretreatment with PBN or the DA uptake inhibitor,
      nomifensin. No effect of nomifensin was seen in the old, because their DA uptake
      mechanisms were already compromised. These results suggest that although age
      related declines in DA uptake may provide some protection against the OS effects
      in muscarinic or 5-HT1A receptors, other factors may increase the vulnerability
      of DA neurons to OS, even with reductions in DA uptake.

PMID- 9586815
TI  - Anticancer quinones induce pRb-preventable G2/M cell cycle arrest and apoptosis.
AB  - Reactive oxygen species generated during the metabolism of the antitumor quinone
      3,6-diaziridinyl-1,4-benzoquinone (DZQ) in human colonic carcinoma HCT116 cells
      lead to the induction of p21 (WAF1, Cip1, or sdi1), an upstream regulator of the
      retinoblastoma gene product pRb involved G1 cell cycle control. We here
      demonstrate that the cell cycle was arrested in G2/M phase following
      supplementation with DZQ of human osteosarcoma Saos-2 cells (lacking both p53 and
      pRb) and HCT116 cells. DZQ also induced p21 and apoptosis in Saos-2 cells. The
      transfection of the Rb gene into Saos-2 cells did not alter the level of p21
      induction, but changed cell cycle arrest into G1 phase and prevented apoptosis.
      These findings suggest that quinones may lead to a p53-independent and pRb
      preventable G2/M arrest and apoptosis, which correlate with p21 induction.

PMID- 9586816
TI  - Superoxide as an intermediate signal for serotonin-induced mitogenesis.
AB  - Serotonin (5-HT) stimulates tyrosine phosphorylation and proliferation of bovine
      pulmonary artery smooth muscle cells (SMC) through its active transport (Lee et
      al, 1991). The present studies show that 5-HT also rapidly elevates O2.-
      formation by these cells within 10 minutes as measured by a lucigenin-enhanced
      chemiluminescence assay. The O2.- free radical quencher, Tiron, and N-acetyl
      cysteine, a substrate for glutathione, block both the 5-HT-induced formation of
      O2.- and cellular proliferation. Similarly, inhibition of 5-HT transport with
      imipramine or treatment of cells with diphenyliodonium, a NAD(P)H oxidase
      inhibitor, block both 5-HT-induced elevation of O2.- and cellular proliferation.
      Alpha-hydroxyfarnesylphosphonic acid, an inhibitor of p21ras, also blocks 5-HT
      induced proliferation. Endothelial cells from the same vessel show neither 5-HT
      induced proliferation nor stimulation of O2.- formation. We conclude that 5-HT
      induced cellular proliferation of SMC through signaling pathways that utilize its
      transport system and O2.- formation.

PMID- 9586817
TI  - Reaction of peroxynitrite with HEPES or MOPS results in the formation of nitric
      oxide donors.
AB  - We investigated the effects of organic buffers on the NO-like biological
      activities of ONOO-. In HEPES buffer (50 mM), ONOO- (1 mM) induced a 20-fold
      increase in endothelial cGMP accumulation and the effect was comparable to that
      elicited by a maximally active concentration of the NO donor DEA/NO. ONOO-
      produced a 12-fold increase of cGMP in MOPS buffer (50 mM), but was virtually
      inactive in phosphate buffer (50 mM). Electrochemical detection of NO showed that
      the biological effects of ONOO- in HEPES or MOPS were due to accumulation of
      compounds that released NO in the presence of copper ions. CuCl2-induced
      formation of NO was completely blocked by the Cu(I) chelator neocuproine but
      unaffected by the Cu(II) chelator cuprizone, pointing to a Cu(I)-catalyzed
      decomposition pathway. Formation of NO from ONOO- was not detectable in phosphate
      buffer, in agreement with the lack of effect of ONOO- on cGMP accumulation in
      this buffer. These data demonstrate that certain buffer components present in
      cell culture media may yield artificial results in experiments with authentic
      ONOO-.

PMID- 9586818
TI  - Concurrent production of reactive oxygen and nitrogen species by airway
      epithelial cells in vitro.
AB  - Intracellularly generated reactive species of both oxygen (ROS) and nitrogen
      (RNS) have been implicated in signaling responses in airway epithelial cells, but
      these radicals have not been measured directly in such cells. In this study,
      intracellular production of both ROS and RNS were measured in the same cell
      lysates of guinea pig tracheal epithelial (GPTE) cells maintained in primary
      culture. ROS and RNS were quantified under basal (constitutive) conditions and in
      response to different stimuli: LPS and TNFalpha [activators of inducible nitric
      oxide synthase (iNOS)]; several activators of calcium-dependent cNOS (ATP,
      bradykinin, ionophore A23187, and thapsigargin); and exogenous oxidant stress
      generated by addition of xanthine oxidase to purine (p + XO). Studies with LPS
      and TNFalpha also were performed using the murine macrophage cell line, RAW
      264.7, as a positive control. Intracellular oxidant production was detected from
      oxidation of dihydrorhodamine to rhodamine. NOx was quantified by either
      chemiluminescent or fluorescent detection. NOS activity was measured as
      citrulline production from arginine. Basal production of oxidants by GPTE cells
      (0.08 + 0.00 nmol rhodamine) was less than 10% that of RAW.267 cells (0.91 + 0.03
      nmol rhodamine). TNFalpha and LPS significantly increased intracellular oxidant
      production in GPTE cells, as did p + XO, but none of the cNOS activators affected
      production of oxidants in these cells. Concentrations of NO2 after 4 h in
      unstimulated RAW 264.7 and GPTE cells were similar and comprised 63% of total NOx
      in GPTE and 62% in RAW cells. TNFalpha and LPS both increased NO2 in GPTE cells,
      but none of the Ca++-mobilizing agents nor p + XO significantly affected
      intracellular RNS. The results suggest both ROS and RNS can be measured in the
      same lysates from airway epithelial cells, and that both ROS and RNS are produced
      in these cells in response to different stimuli.

PMID- 9586819
TI  - Oxidative stress developed during the reperfusion of ischemic myocardium induces
      apoptosis.
AB  - Apoptosis or programmed cell death is a genetically controlled response for cells
      to commit suicide and, is associated with DNA fragmentation or laddering. The
      common inducers of apoptosis include oxygen free radicals/oxidative stress and
      Ca2+ which are also implicated in the pathogenesis of myocardial ischemic
      reperfusion injury. To examine whether ischemic reperfusion injury is mediated by
      apoptotic cell death, isolated perfused rat hearts were subjected to 15, 30 or 60
      min of ischemia as well as 15 min of ischemia followed by 30, 60 or 120 min of
      reperfusion. At the end of each experiment, hearts were processed for the
      evaluation of apoptosis, DNA laddering. Apoptosis was studied by visualizing the
      apoptotic cardiomyocytes by direct fluorescence detection of digoxigenin-labeled
      genomic DNA using APOPTAG in situ apoptosis detection kit. DNA laddering was
      evaluated by subjecting the DNA obtained from the hearts to 1.8% agarose gel
      electrophoresis and photographed under UV illumination. The results of our study
      revealed apoptotic cells only in the 60 and 120 min reperfused hearts as
      demonstrated by the intense fluorescence of the immunostained digoxigenin-labeled
      genomic DNA when observed under fluorescence microscopy. None of the ischemic
      hearts showed any evidence of apoptosis. These results corroborated with the
      findings of DNA fragmentation which showed increased ladders of DNA bands in the
      same reperfused hearts representing integer multiples of the intenucleosomal DNA
      length (about 180 bp). The presence of apoptotic cells and DNA fragmentation in
      the myocardium were abolished by preperfusing the hearts in the presence of
      ebselen, which also removed the oxidative stress developed in the heart. Taken
      together, these results clearly demonstrate that oxidative stress developed in
      the ischemic reperfused myocardium induces apoptosis.

PMID- 9586820
TI  - Analysis of gastroduodenitis and oesophagitis in relation to dyspeptic/reflux
      symptoms.
AB  - BACKGROUND/AIMS: The pathogenesis of dyspeptic/reflux symptoms and the clinico
      pathologic profile of affected patients are still poorly understood. To improve
      our knowledge in this field we carried out a systematic, comparative analysis of
      symptom profiles and histopathologic patterns of oesophagogastroduodenal mucosa
      in a series of 221 subjects, 140 with and 81 without endoscopic evidence of
      hiatal hernia. Of these, 190 showed reflux and/or dyspeptic symptoms. METHODS:
      Before endoscopy, all the subjects were questioned about the presence and
      severity of 12 individual symptoms. Biopsies were taken from the distal
      oesophagus, cardia, corpus, angulus, antrum and duodenal bulb, and were scored in
      accordance with the Sydney system. RESULTS: Patient groups with a distinct
      clinico-pathologic profile were better identified when symptoms of adequate
      severity were compared with histopathologic parameters. A correlation between
      gastroesophageal reflux disease (GORD) symptoms and histologic signs of
      oesophagitis was mostly restricted to patients endoscopically positive for
      oesophagitis. Retroxiphoid pyrosis correlated with cardial gastritis but not with
      oesophagitis, either endoscopic or histologic, while ulcer-like epigastric pain
      correlated with active duodenitis and distal gastritis. No definite
      histopathologic background was detected in patients with putative dysmotility
      like symptoms, endoscopy-negative GORD and low score or mixed symptoms.
      CONCLUSION: A contribution of Helicobacter pylori gastroduodenitis to the
      pathogenesis of some dyspeptic symptoms seems likely. However, the identification
      of specific histologic changes causing individual symptoms remains rather
      elusive, with the exception of active antroduodenitis in patients with ulcer-like
      pain and of active proximal gastritis in patients with severe retroxiphoid
      pyrosis.

PMID- 9586821
TI  - Increased hepatocyte growth factor content in rat stomach during omeprazole
      treatment.
AB  - BACKGROUND AND AIMS: Hepatocyte growth factor (HGF) is a potent mitogen of
      gastric epithelial cells, and its production is stimulated during the healing of
      gastric mucosal lesions. In this study, the effect of a proton pump inhibitor,
      omeprazole, on the production and degradation of HGF in the stomach was examined
      to elucidate the mechanism of the omeprazole-induced acceleration of gastric
      mucosal healing. METHODS: Indomethacin-induced gastric mucosal lesions were
      induced in rats with or without omeprazole pretreatment. HGF gene expression and
      the content of HGF was investigated in the rat stomach. HGF degradation by
      gastric juice was also tested. RESULTS: In omeprazole-treated rats, the healing
      of gastric mucosal lesions was accelerated in comparison with those of untreated
      rats. Although omeprazole treatment did not enhance the indomethacin-induced
      increase in HGF gene expression, it significantly augmented the gastric HGF
      content. Furthermore, omeprazole increased the gastric content not only of the
      inactive but also of the active heterodimeric form of HGF, and this appeared to
      be due to the inhibition of the HGF degradation by gastric juice. CONCLUSION:
      Omeprazole-induced acceleration of gastric mucosal healing may be mediated at
      least in part by the reduced degradation of HGF in the stomach.

PMID- 9586822
TI  - Comparison of epidermal growth factor and transforming growth factor-beta1
      expression in hormone-induced acute pancreatitis in rats.
AB  - Overexpression of transforming growth factors (TGF) in acute pancreatitis (AP)
      suggested that these substances play an important role in pancreatic repair and
      remodeling but the contribution of epidermal growth factor (EGF), that is well
      known to promote cell growth and regeneration, has not been investigated. The aim
      of this study was to compare the gene and immunohistochemical expression of EGF
      and TGF-beta1, cell proliferation, and biochemical parameters in AP induced by
      infusion of a supramaximal dose of caerulein in rats. The rats were sacrificed at
      0, 12, 24, 48, 72 h, 5 and 10 days after the termination of caerulein infusion.
      Pancreatic tissue DNA synthesis, cell proliferation, histological and
      immunohistochemical assessments and plasma amylase were estimated following
      induction of AP. The mRNA expression for EGF and TGF-beta1 was evaluated by
      reverse transcription-polymerase chain reaction. During 10 days of the study
      after induction of AP a gradual normalization of biochemical and histological
      parameters was observed. DNA synthesis and cell proliferation which were
      significantly decreased at 0 and 24 h, increased significantly at 48 and 72 h,
      and then gradually decreased reaching at day 10 the values similar to those of
      vehicle-treated control rats. In these control rats the EGF mRNA or
      immunohistochemical expression was not detected, while the TGF-beta1 expression
      was weak. After induction of AP, the mRNA and immunohistochemical expression of
      EGF showed an increase during the initial 5 days, while those of TGF-beta1 showed
      a marked increase between 0 and 48 h and then again at day 10. We confirm that:
      (1) the expression of TGF-beta1 during AP is biphasic with an initial increase
      probably related to pancreatic damage and inhibition of cell proliferation and
      with the later phase of increase accompanied by the stimulation of the synthesis
      of extracellular matrix components and (2) AP is accompanied by an induction of
      synthesis of EGF that occurs in the initial phase of AP, probably limiting the
      extent of AP, and enhancing the stimulation of the pancreatic repair and
      regeneration.

PMID- 9586824
TI  - Neural control of the gallbladder: an intracellular study of human gallbladder
      neurons.
AB  - BACKGROUND/AIMS: Gallbladder neurons are important governors of gallbladder
      function. In animal models, gallbladder ganglia can be regulated both by neural
      and hormonal inputs. The purpose of this study was to demonstrate the feasibility
      of obtaining recordings from human gallbladder neurons. METHODS: Human
      gallbladders (n = 33) were bathed in oxygenated Krebs solution (37 degrees C)
      containing the vital fluorescent stain 4-Di-2-ASP to localize the ganglia. Cells
      were characterized using conventional intracellular recording techniques.
      RESULTS: The mean resting membrane potential of human gallbladder neurons was 
      51.2 +/- 1.8 mV (n = 11). Depolarizing current pulses elicited only 1-4 spikes
      regardless of the amplitude or duration of the stimulus. Afterspike
      hyperpolarizations had a mean duration of 144.5 +/- 19.2 ms (n = 10). Anodal
      break excitation was not recorded with hyperpolarizing current pulses. Fiber
      tract stimulation elicited fast excitatory postsynaptic potentials in all neurons
      tested. CONCLUSION: Intracellular recordings of human gallbladder neurons
      utilizing 4-Di-2-ASP are thus feasible, but are very problematic due to the
      density of connective tissue overlying the ganglia. As human and guinea pig
      gallbladder neurons have similar basic electrical properties, the guinea pig may
      be an appropriate model for further electrophysiological studies into gallbladder
      disease.

PMID- 9586823
TI  - K-ras mutations at codon 12 are rare events in chronic pancreatitis.
AB  - BACKGROUND/AIMS: The activation of the K-ras gene at codon 12 is thought to be an
      early genetic event in the multistep pathogenesis of pancreatic cancer. Since the
      risk of pancreatic cancer is significantly elevated in subjects with chronic
      pancreatitis, the aim of the present study was to determine the frequency of K
      ras mutations in chronic pancreatitis. METHODS: Pancreatic DNA from
      intraoperatively resected tissues of 60 patients with chronic pancreatitis and 11
      patients with histologically confirmed pancreatic carcinoma was evaluated by PCR
      amplification and restriction fragment length polymorphism analysis. RESULTS: In
      none of the 60 samples of chronic pancreatitis could K-ras mutations be
      identified using two independent PCR assays. In 5 of 11 patients with pancreatic
      carcinoma, K-ras mutations in codon 12 were detected. CONCLUSION: These data
      indicate that K-ras mutations are rare events in chronic pancreatitis.
      Alternatively, it is possible that the time span between the occurrence of K-ras
      mutations and malignant transformation is rather short.

PMID- 9586825
TI  - Intestinal absorption and enterohepatic circulation of folic acid: effect of
      ethanol.
AB  - This study sought to determine the intestinal in vivo absorption of folic acid by
      the whole intestine, and the appearance of this compound in bile in control and
      ethanol-fed rats. Intestinal folic acid absorption in rats with the bile duct
      cannulated decreased in ethanol-fed rats with respect to control rats. This
      difference was significant at 1 and 2.5 microM concentrations of folic acid. This
      result is in contrast with previous work in our laboratory on rats with intact
      bile ducts, where ethanol-fed rats had an increase in folic acid absorption. The
      results obtained in the present work suggest an impaired enterohepatic recycling
      of folic acid in ethanol-fed rats.

PMID- 9586826
TI  - Anastomotic blood-flow reduction in rat small intestine with chronic radiation
      damage.
AB  - BACKGROUND/AIMS: Anastomoses in previously irradiated intestine are prone to
      leakage, possibly due to an impeded blood supply. Whether or not chronic
      radiation damage actually predisposes to a disturbed blood flow in the vicinity
      of anastomoses was investigated in the rat small bowel. METHOD: A 2-cm segment of
      rat ileum was irradiated with a single dose (21 Gy). After 20 weeks an
      anastomosis was created in the irradiated segment and in the corresponding
      segment of controls. Another 4 days later local blood flow was studied with the
      14C-iodoantipyrine autoradiography technique in 16 sectors around the
      circumference both in the anastomotic segment and in a segment 4 mm apart.
      RESULTS: In the anastomotic segment, the average blood flow was reduced in
      irradiated compared with non-irradiated animals in the mucosal layer (p = 0.034),
      but not in the muscular layer (p = 0.08). In the mesenteric quadrant blood flow
      was reduced in irradiated compared with non-irradiated animals, both in the
      mucosal layer (p = 0.012) and in the muscular layer (p = 0.05). More irradiated
      than non-irradiated animals showed a blood-flow reduction to 15% or more in 13-16
      sectors both in the mucosal (p = 0.015) and the muscular layer (p = 0.04).
      CONCLUSIONS: The results favor the hypothesis that anastomoses in previously
      irradiated intestine are vascularly compromized and thereby have an increased
      risk of leakage.

PMID- 9586827
TI  - Colon epithelium can be transiently transfected with liposomes, calcium phosphate
      precipitation and DEAE dextran in vivo.
AB  - BACKGROUND: The introduction of recombinant DNA into cells is the initial step
      toward the development of gene therapy. It has been shown that cationic liposomes
      are useful vehicles to introduce DNA into colon epithelial cells in vivo.
      METHODS: In the present study we compared the efficacy of different nonviral
      transfection methods into the colon wall. In anesthetized rats, a double balloon
      catheter was advanced into the colon and a chloramphenicol acetyltransferase
      (CAT) reporter plasmid complexed to liposomes, mixed with DEAE dextran, or
      precipitated with calcium phosphate was instilled. Following 2 days CAT activity
      was determined in the transfected colon segments. RESULTS: DEAE dextran and
      liposomes were more effective than calcium phosphate, whereas naked DNA was not
      taken up by the colon epithelial cells. Reporter gene expression was dose
      dependent. Expressing cell types did not differ utilizing the various
      transfection methods as judged by X-gal staining of colon sections after
      transfection with a LacZ reporter plasmid. CONCLUSION: These data indicate that
      in addition to liposomes, plasmid DNA mixed with DEAE dextran can be taken up by
      colon epithelial cells. This transfection techniques may prove useful in the
      development of gene therapy approaches for colon disease.

PMID- 9586829
TI  - Chlamydia trachomatis infection: is it relevant in irritable bowel syndrome?
AB  - BACKGROUND: Irritable bowel syndrome can present with gynaecological symptoms
      similar to those of chronic pelvic inflammatory disease, which is commonly caused
      by Chlamydia trachomatis. Infection with this organism might therefore lead to
      diagnostic and management difficulties in patients, not only as a result of
      symptom overlap between the two disorders but also because chlamydial infection
      might exacerbate the symptoms of irritable bowel syndrome. This study was
      designed to investigate any possible link between chlamydial infection and
      irritable bowel syndrome. PATIENTS/METHODS: The prevalence of antibodies to C.
      trachomatis and abdominal symptomatology was assessed in a group of 100 female
      patients with irritable bowel syndrome and 100 matched female controls. RESULTS:
      25% of patients and 17% of controls were found to have evidence of previous
      chlamydial infection. This difference was not statistically significant. Within
      the patient group, no association was found between chlamydial infection and any
      particular pattern of symptomatology. CONCLUSIONS: The results of this study
      indicate that occult chlamydial infection is not a major problem in irritable
      bowel syndrome and that routine investigation for this organism is unnecessary.
      They also provide some reassurance that pelvic inflammatory disease and all its
      potentially serious consequences is not being significantly overlooked in
      gastroenterological practice.

PMID- 9586828
TI  - Growth and recurrence of colorectal polyps: a double-blind 3-year intervention
      with calcium and antioxidants.
AB  - BACKGROUND: Dietary calcium and antioxidants have been suggested as protective
      agents against colorectal cancer. This has been supported by animal experimental
      studies, case control and cohort studies. MATERIALS AND METHODS: In a prospective
      intervention study of colorectal adenomas, and intermediary stage in colorectal
      carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily
      mixture of beta-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101
      microg, and calcium (1.6 g daily) as carbonate for a period of 3 years with
      annual colonoscopic follow-up to test if the mixture was able to reduce polyp
      growth or recurrence. All polyps of < 10 mm at enrollment or follow-up were left
      unresected until the end of the study. RESULTS: 87-91% of the patients attended
      the annual endoscopic follow-up investigations, and 19% of the patients dropped
      out of the medical intervention. The rest consumed 85% of the total amount of
      tablets over the 3 years. The fecal calcium concentration was 2.3-2.7 times
      higher in patients taking active medication compared to the placebo group. Diet
      registration showed that, when adding the intake of antioxidants and calcium from
      diet and intervention, there was a significant difference between the intake of
      these substances in the active and the placebo group. No difference was detected
      in the growth of adenomas between the active and the placebo group from year to
      year and for the total study period. Moreover, there was no effect on polyps of <
      5 or 5-9 mm, or on polyps in the different colonic segments analyzed separately.
      A reduced growth of adenomas was found in patients <60 years of age taking active
      medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3
      mm; 95% CI 0.26-4.36). There was a significantly lower number of patients free of
      new adenomas in the placebo group compared to those taking active medication as
      tested by logistic regression and Kaplan-Meier analysis (log-rank test p value
      0.035). Subgroup analysis showed that only the group of patients with no family
      history of colorectal cancer, those with only one adenoma at inclusion, and those
      <65 years benefitted from the intervention medication. CONCLUSION: The study did
      not find an overall effect on polyp growth. Our data, however, may support a
      protective role of calcium and antioxidants on new adenoma formation.

PMID- 9586830
TI  - Gastric carcinoid with histamine production, histamine transporter and expression
      of somatostatin receptors.
AB  - A case of sporadic, histamine-producing gastric carcinoid with liver metastases
      is reported. The patient was treated with somatostatin analogue (octreotide)
      combined with cortisone and blockade of histamine receptors prior to surgery,
      which included subtotal gastrectomy, excision of lymph node metastases and
      superficial liver metastases. Residual liver metastases were injected with
      ethanol. These interventions markedly reduced the urinary excretion of the main
      histamine metabolite (MelmAA). Eighteen months later combined immuno- and
      chemotherapy was initiated due to tumour progression and recurrent hormonal
      symptoms with good clinical results over 12 months. Scintigraphy, using 111In
      DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary
      tumour, lymph node metastases and liver metastases. The tissue/blood 111In
      concentration ratios of tumour biopsies were very high. Northern analyses
      confirmed expression of all subtypes of sstr1-5. Immunocytochemically, tumour
      cells were strongly positive for chromogranin A, histamine and vesicular
      monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1,
      suggesting an origin from gastric enterochromaffin-like cells. In primary tumour
      cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in
      conditioned culture medium, indicating a defective decarboxylation of the
      tryptamine precursor. This rare case of histamine-producing gastric carcinoid
      demonstrates that excellent symptom relief can be achieved despite disseminated
      disease, if active, multimodal treatment strategy is instituted. The presence of
      high numbers of sstr in tumour tissue also raises the possibility of receptor
      guided radiotherapy.

PMID- 9586832
TI  - Selectively bred lines of rats differ in social interaction and hippocampal 5
      HT1A receptor function: a link between anxiety and depression?
AB  - Selective breeding for high and low sensitivity to the hypothermic response of
      the 5-HT1A receptor agonist 8-OH-DPAT has established two lines (HDS and LDS,
      respectively) whose behavior differs in a model of depression, but not in the
      elevated plus-maze test of anxiety. The lines also differed in postsynaptic, but
      not presynaptic, 5-HT1A receptors. Based on previous evidence that postsynaptic 5
      HT1A receptors mediate anxiogenic effects in the social interaction test of
      anxiety, but not the elevated plus-maze, we investigated possible differences
      between the lines in these two tests. The HDS line had a consistently lower level
      of social interaction compared with the LDS line, but no differences were found
      on any of the measures of the anxiety on trials 1 or 2 in the elevated plus-maze.
      To determine whether the line differences in anxiety were mediated by different
      hippocampal 5-HT1A receptor function, 8-OH-DPAT (50 and 100 ng) was applied
      bilaterally to the dorsal hippocampus. This elicited anxiogenic effects in the
      LDS line, as has been previously reported in other rat strains, but there was no
      response in the HDS line, thus demonstrating an abnormal 5-HT1A receptor function
      in the hippocampus. The 5-HT1A receptor antagonist WAY100635 (200 ng) was
      administered to the dorsal hippocampus to test for possible differences between
      the lines in 5-HT tone. There were no significant changes in social interaction
      in either the HDS or LDS rats, indicating that the different level of anxiety
      between lines is not due to differences in hippocampal 5-HT tone. It is proposed
      that the HDS line may prove a useful model of a type of high trait anxiety linked
      to a susceptibility to depression.

PMID- 9586835
TI  - Strain differences in open-field and elevated plus-maze behavior of rats without
      and with pretest handling.
AB  - Behavior of two rat strains was analyzed with and without 1-week pretest
      handling. Male rats (150-200 g body weight) of the strains PVG/OlaHsd (PVG) and
      Hsd:Sprague-DawleySD (SPRD) were tested once in a standard open field and an
      enriched open field and twice in an elevated plus-maze. Behavioral analysis
      revealed significant differences between the two strains and differential effects
      of the pretest handling procedure. SPRD rats displayed higher levels of activity
      and exploratory behavior than the PVG rats, whereas PVG rats were obviously less
      anxious. One-week pretest handling had an "anxiolytic" effect and changed
      activity and exploration-related behavior of the animals in both strains.
      Activity-related parameters were mainly affected in SPRD rats and anxiety-related
      ones in PVG rats. The data give evidence that differences in behavior of rats are
      not only determined genetically but also by preceding handling procedures.
      Because the two rat strains responded differentially to the pretest handling, we
      recommend to use a well-defined handling procedure before starting a behavioral
      test, especially when drug applications are included.

PMID- 9586831
TI  - Cholinergic/serotonergic interactions in hypothermia: implications for rat models
      of depression.
AB  - This article reviews published reports and presents new evidence that support a
      number of commonalties between lines of rats selectively bred for differences in
      cholinergic (muscarinic) and serotonergic (5-HT1A) sensitivity. The Flinders
      Sensitive Line (FSL) rat, a genetic animal model of depression derived for
      cholinergic supersensitivity, is more sensitive to both cholinergic and
      serotonergic agonists, and exhibits exaggerated immobility in the forced swim
      test relative to the control, Flinders Resistant Line (FRL), rat. Similar
      exaggerated responses are seen in a line of rats recently selected for increased
      sensitivity to the 5-HT1A agonist, 8-OH-DPAT (High DPAT Sensitive--HDS), relative
      to lines selectively bred for either low (Low DPAT Sensitive--LDS) or random
      (Random DPAT Sensitive--RDS) sensitivity to 8-OH-DPAT. For both the FSL and HDS
      rats, their exaggerated immobility in the forced swim test is reduced following
      chronic treatment with antidepressants. The present studies examined further the
      interaction between cholinergic and serotonergic systems in the above lines.
      Supersensitive hypothermic responses to 8-OH-DPAT were observed very early
      (postnatal day 18) in FSL rats, suggesting that both muscarinic and serotonergic
      supersensitivity are inherent characteristics of these rats. Scopolamine, a
      muscarinic antagonist, completely blocked the hypothermic effects of the
      muscarinic agonist oxotremorine in FSL and FRL rats, but had no effect on the
      hypothermic responses to 8-OH-DPAT, suggesting an independence of muscarinic and
      5-HT1A systems. On the other hand, genetic selection of genetically heterogeneous
      rats for differential hypothermic responses to the muscarinic agonist
      oxotremorine were accompanied by differential hypothermic responses to 8-OH-DPAT,
      suggesting an interaction between muscarinic and 5-HT1A systems. Overall, these
      studies argue for an inherent interaction between muscarinic and 5-HT1A systems,
      which probably occurs beyond the postsynaptic receptors, possibly at the level of
      G proteins.

PMID- 9586834
TI  - Differential effects of prenatal stress in two inbred strains of rats.
AB  - The long-term effects of prenatal stress (three times daily restraint stress
      during the last week of gestation) on the behavioral response to stress, as
      assessed by novelty-induced locomotion, performance in the forced swim test, and
      the acquisition of a two-way active avoidance, were investigated in two inbred
      strains of rats, Fischer 344 (F344/NHsd/Zur) and Lewis (LEW/SsNHsd/Zur).
      Additional measures included birth weights, pain threshold on the hot plate, and
      basal and stress-induced corticosterone secretion. In all of the behavioral
      paradigms strain differences were found: LEW rats showed poorer acquisition of
      avoidance conditioning, displayed higher levels of activity on the open plate,
      less immobility time in the forced swim test, and lower pain thresholds in the
      hot-plate test compared with F344 rats. LEW rats had higher birth weights after
      prenatal stress, whereas F344 rats were lighter. Following prenatal stress the
      pattern of behavioral effects obtained in LEW rats in stress-related tests could
      be interpreted as improved coping abilities with stress, i.e., improved
      acquisition of active avoidance, less immobility in the forced swim test, and
      reduced novelty-induced locomotion. Prenatal stress was much less effective in
      inducing long-term behavioral changes in F344 rats, yielding only one effect,
      namely, enhanced novelty-induced locomotion in female F344 rats. Pain thresholds
      were increased as a consequence of prenatal stress, irrespective of strain and
      gender. Basal and stress-induced corticosterone release differed in the two
      strains, with LEW rats showing less stress-induced corticosterone release.
      Prenatal stress did not, however, affect basal or stress-induced corticosterone
      release. The results suggest that prenatal stress exerts long-term effects on
      behavior, which depend on the genetic background.

PMID- 9586836
TI  - Rat strain differences in open-field behavior and the locomotor stimulating and
      rewarding effects of amphetamine.
AB  - Fischer 344 (F344) and Lewis (LEW) rats show considerable neuroanatomical and
      neurophysiological differences within the mesolimbic dopamine system. The aim of
      our experiments was to study the functional correlates of such differences by
      examining open-field behavior and the sensitivity towards the psychostimulant and
      rewarding effects of amphetamine in male and female, F344 and LEW rats. In
      addition, the consequences of short versus extended habituation to open-field
      testing on amphetamine locomotion in these two rat strains was assessed. LEW but
      not F344 rats irrespective of gender showed between-session habituation of open
      field activity. Amphetamine-induced locomotion was higher in F344 compared to LEW
      rats and in females compared to male rats. In addition, extended habituation
      increased the locomotor effects of amphetamine. The rewarding effects of
      amphetamine as measured by the conditioned place preference test were more
      pronounced in F344 than in LEW rats. Our results suggest that the two rat strains
      differed in their behavioral response to mild stress and to amphetamine and that
      these differences may depend upon differences within the mesolimbic dopamine
      system.

PMID- 9586833
TI  - Specific [3H]8-OH-DPAT binding in brain regions of rats genetically predisposed
      to various defense behavior strategies.
AB  - Distribution of 5-HT1A receptors was studied in rats genetically predisposed to
      two basic defense strategies--passive (freezing) or active (aggression) defensive
      behavior. Specific [3H]8-OH-DPAT binding was assayed in the brain structures of
      rat strains bred for 40 generations from Wistar stock for predisposition to
      freezing (catalepsy), and in wild rats bred for low and high aggression to
      humans. Considerable changes in [3H]8-OH-DPAT binding were found in the brain of
      rats with hereditary predisposition to catalepsy. A significant decrease in Bmax
      of specific receptor binding of [3H]8-OH-DPAT in the frontal cortex, and in the
      striatum as well as an increase in Kd in the hippocampus of cataleptic rats was
      shown. A clear-cut tendency to decrease of 5-HT1A receptor density was observed
      in the midbrain and hypothalamus of these rats. A comparison of wild Norway rats
      bred for aggressiveness against humans with those bred for the absence of
      affective aggressiveness showed a Bmax decrease without Kd change in the frontal
      cortex, hypothalamus, and amygdala of aggressive animals. It is hypothesized that
      5-HT1A and probably 5-HT1A-like 5-HT7 serotonin receptors are involved in the
      mechanisms of both active and passive defense reactions, and the high expression
      of fear-induced defense is associated with their decrease in the frontal cortex.
      At the same time, the genetically determined preference for a certain defense
      behavior strategy depends either on the peculiarities of distribution of these
      receptor types in the brain regions or on some other types of serotonin
      receptors.

PMID- 9586837
TI  - Prenatal stress effects are partially ameliorated by prenatal administration of
      the neurosteroid allopregnanolone.
AB  - This study examined the effects of exposure to prenatal stress on young and adult
      rats, and whether the concomitant administration of an anxiolytic neurosteroid,
      allopregnanolone (3-alpha-hydroxy-5 alpha-pregnan-20-one), could ameliorate some
      of the behavioral dysfunctions associated with prenatal stress. Pregnant dams
      were assigned to one of five treatment groups on gestational day 14. These groups
      were exposed to either 1) restraint for 45 min three times daily; 2) a vehicle
      injection twice daily; 3) 5 mg/kg allopregnanolone twice daily; 4) restraint with
      allopregnanolone injections; or 5) nonhandled controls. Assays for plasma
      allopregnanolone concentrations indicated that exogenous allopregnanolone
      injections significantly raised circulating levels to a comparable degree in
      gestational day 20 dams and their fetuses. At 7 days of age, however, subjects
      prenatally exposed to allopregnanolone either alone or with restraint now had
      lower circulating levels compared to the other groups, suggesting some negative
      compensatory change. Behavioral results suggested that the effects of prenatal
      stress on affective behaviors (ultrasonic vocalizations emitted after a brief
      maternal separation at 7 days of age, and plus-maze behavior at 70 days of age)
      could be reversed by coadministration of allopregnanolone. When locomotor
      activity was assessed at 16 and 60 days of age, no comparable reversal effect was
      observed. In fact, the allopregnanolone groups had results similar to those of
      the restraint alone group. Thus, for some neuronal systems, allopregnanolone may
      exert either a direct teratogenic effect or an indirect effect due to
      neurosteroid-induced behavioral changes in the pregnant dam.

PMID- 9586838
TI  - Changes in the neuronal membranes of mice related to steroid hormone influences.
AB  - Changes in the biochemical composition of synaptosomal plasma membranes (SPM)
      isolated from mouse brains have been measured. The protein, phospholipid, and
      cholesterol contents all increased over the first 30 days of postnatal life, with
      the cholesterol to phospholipid molar ratio (one of the major determinants of
      lipid fluidity) also increasing in direct relation to the decrease in lipid
      fluidity. The fatty acid composition of SPM also changes with the increase in
      18:0, and the decrease in 18:2, 18:3, and 22:4, in keeping with the increase in
      membrane order. Steroid hormones alter lipid fluidity to a greater degree in
      fluid membranes, indicating that the nongenomic effects of steroids will be most
      prevalent in membranes during the early prenatal period and for the first days
      following birth. The potential effects of xenobiotics on membrane fluidity are
      also discussed.

PMID- 9586840
TI  - A CCK(A)-receptor antagonist administered to the neonate alters mother-infant
      interactions in the rat.
AB  - The importance of the infant's cholecystokinin (CCK) system for eliciting optimal
      maternal care was examined in 6-9-day-old Sprague-Dawley rats. After
      administration of either vehicle, CCK-8 (1 or 8 microg/kg) or devazepide (1
      mg/kg; a selective CCK(A) receptor antagonist), pups were either individually
      isolated (Experiment 1) or individually reunited with their dam (Experiment 2)
      and the rats' behavior was observed. When isolated, pups that received devazepide
      displayed significantly more head-lifting and wall-climbing attempts than vehicle
      treated controls, suggesting that endogenous CCK dampens activity. Devazepide
      treated rats were found more frequently in proximity with their mothers when
      reunited with them, and they emitted more ultrasonic vocalizations compared to
      vehicle controls. Pups treated with 1 microg/kg CCK received less body licking
      than vehicle controls. In addition, dams hovered and crouched over devazepide
      treated pups more than over pups treated with 1 microg/kg CCK. The results
      suggest that endogenous CCK has a calming, quieting effect in the neonatal pup
      and that this, in turn, results in less infant-mother attractivity and reduced
      levels of maternal care.

PMID- 9586839
TI  - Effects of prenatal morphine exposure on NK cytotoxicity and responsiveness to
      LPS in rats.
AB  - Prenatal exposure to opiates can adversely affect fetal development, resulting in
      long-term growth retardation and impairments in physiological and behavioral
      functions. In the present study we studied long-term effects of prenatal morphine
      exposure on immune functions, including the activity of natural killer (NK) cells
      and the febrile and behavioral responses to lipopolysaccharide (LPS). Pregnant
      Fischer 344 rats were given increasing doses of morphine in slow release emulsion
      during gestational days 12-18. Control rats were injected with vehicle and were
      either pair fed to morphine rats or fed ad lib. Postnatal experiments were
      conducted when offspring were 10-12 weeks old. Compared to both control groups,
      rats prenatally exposed to morphine exhibited: 1) suppressed cytotoxic activity
      of NK cells; 2) reduced LPS-induced fever measured by a biotelemetric system; 3)
      reduced hyperalgesia measured by the hot-plate test at 30 min, and augmented
      hypoalgesia at 2-6 h post-LPS; 4) higher open-field activity in saline-treated
      animals, and more pronounced suppression of activity in LPS-injected animals; 5)
      LPS-induced reduction of food consumption, body weight, and social exploration,
      which did not differ from the reduction observed in control animals. These
      findings indicate that prenatal exposure to morphine induces long-term impairment
      of host-defense mechanisms, which may render the offspring more susceptible to
      infectious diseases.

PMID- 9586841
TI  - Early maternal separation increases NGF expression in the developing rat
      hippocampus.
AB  - Nerve Growth Factor (NGF) is a neurotrophin involved in growth and
      differentiation of central cholinergic neurons. In this study a maternal
      separation paradigm was used to test whether levels of NGF might be affected by
      brief manipulations of rat pups early during ontogeny. The expression of NGF mRNA
      was examined in 3-day-old rat pups following 45 min maternal separation using in
      situ hybridization. Early maternal separation in neonatal rats resulted in
      increased expression of NGF mRNA in the dentate gyrus and the hilus of the
      hippocampus. NGF protein levels measured (by means of a sensitive ELISA assay) in
      the whole hippocampus the day following the separation procedure did not differ
      in separated vs. nonseparated pups. These data indicate that brief manipulations
      performed early during development can affect hippocampal NGF expression.

PMID- 9586843
TI  - Long-term effects of repeated maternal separation on three different latent
      inhibition paradigms.
AB  - In the present study we investigated the effect of repeated maternal separation
      on postnatal days 12, 14, 16, and 18 for 6 h/day on Wistar rats on three latent
      inhibition (LI) paradigms: two-way active avoidance, conditioned emotional
      response (CER), and conditioned taste aversion (CTA). In addition, hyperactivity
      induced by d-amphetamine and stereotypies induced by apomorphine were evaluated.
      In all three LI experiments, the control animals showed only marginal LI, whereas
      the maternally separated animals showed enhanced LI (only males in CTA). In two
      way active avoidance within the nonpreexposed condition maternally separated
      animals showed improved acquisition of avoidance learning compared with the
      control animals. Sensitivity in response to amphetamine and apomorphine was not
      altered by the maternal separation procedure. Thus, maternal separation in this
      study, contrary to previous reports, but in line with results obtained following
      early handling before weaning, led to enhancement of the LI phenomenon as
      assessed in each of the three procedures. As our maternal separation procedure (6
      h on days 12, 14, 16, and 18) led to behavioral outcomes that differed from those
      reported by Ellenbroek and Cools (24 h on day 10), it is suggested that maternal
      separation regimens that are dissimilar may lead to different and sometimes
      opposite behavioral effects.

PMID- 9586844
TI  - The disruption of prepulse inhibition by social isolation in the Wistar rat: how
      robust is the effect?
AB  - Postweaning isolation rearing in rats is shown to have consequences for the
      expression of numerous behaviors. The present studies investigated isolation
      induced disruptions of the prepulse inhibition (PPI) response in the Wistar rat
      strain, as a function of exposure of the animals to locomotor activity testing.
      Further, repeated testing of PPI was investigated to examine the robustness of
      the isolation-induced disruptions. The results indicate that experimentally naive
      isolation-reared animals exhibit disruptions in the PPI response that are
      retained in a second test 7 days later. The disruptions obtained are shown to be
      consistent across all pulse frequencies examined and independent of effects on
      startle. Exposure to activity testing, however, either before or after the
      measurement of PPI, abolished the isolation-induced disruption of PPI in a
      subsequent test. In contrast, locomotor activity testing consistently revealed a
      hyperactivity response in isolation-reared animals that was not influenced by the
      temporal occurrence of the testing. The findings are discussed relative to the
      interpretation of data emerging from studies where both activity testing and PPI
      are performed in the same animals, and in the relation to the use of PPI in
      isolation-reared animals as representing a nonpharmacological animal model of
      schizophrenia.

PMID- 9586845
TI  - Dynamic alterations of serotonergic metabolism and receptors during social
      isolation of low- and high-active mice.
AB  - Alterations induced by social isolation (1 day to 18 weeks) in low- and high
      active mice (LAM and HAM) were studied in respect to serotonin metabolism, [3H]-8
      OH-DPAT binding of presynaptic (midbrain), postsynaptic (hippocampus) 5-HT1A
      receptors and [3H]-ketanserin binding of cortical 5-HT2A receptors. Individual
      housing of mice was associated with reduction of serotonin metabolism, depending
      on isolation time and brain structure. Whereas a transient decrease in the
      striatum and cortex was detected between 1 week and 6 weeks, reduction of
      cerebellar and hippocampal serotonin metabolism was found later (12-18 weeks).
      Serotonergic systems of HAM were found to be more reactive to environmental
      disturbances, and their serotonin metabolism was more affected by social
      isolation. Isolation-induced upregulation of cortical 5-HT2A receptors was
      measured only in HAM. Densities of postsynaptic 5-HT1A receptors in the
      hippocampus did differ either in grouped or isolated mice. However, there were
      significant differences in hippocampal 5-HT1A receptor affinity, especially
      between 1 day and 3 weeks. Transient downregulation of presynaptic 5-HT1A
      receptors in the midbrain was found in isolated mice between 3 and 6 weeks. These
      results are discussed in terms of interactions between serotonergic alterations
      and isolation-induced aggression.

PMID- 9586842
TI  - Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic
      systems.
AB  - Isolation rearing of rats produces a behavioral syndrome indicative of altered
      dopamine (DA) function in the nucleus accumbens (NAC). The present experiments
      extend these findings by investigating: (a) interactions between isolation
      rearing and repeated handling/testing on presynaptic DA function in the NAC using
      in vivo microdialysis: (b) the dose-response curve for the effects of d
      amphetamine, and the responses elicited by high potassium, using in vivo
      microdialysis, and (c) postsynaptic function in isolates as indexed by DA
      receptor-linked cAMP production. Experiment 1 showed that both isolation rearing
      and repeated handling/testing had effects on monoamine function in the NAC.
      However, while both manipulations enhanced DA release evoked by d-amphetamine,
      only isolated rats had elevated basal DA levels. Opposite neurochemical changes
      were observed with respect to the serotonin metabolite 5-HIAA, isolates having
      lower, and repeatedly handled/tested animals having higher, extracellular levels.
      Experiment 2 provided evidence for enhanced d-amphetamine-evoked DA release in
      isolated animals, while potassium-evoked DA release was reduced. Experiment 3
      provided evidence that the isolation rearing induced changes in presynaptic DA
      function were accompanied by postsynaptic changes. Specifically, the inhibitory
      influence of the D2 receptor on D1 receptor-stimulated cAMP production was
      attenuated in ventral striatal slices taken from isolates, suggesting a
      functional downregulation of D2 receptors.

PMID- 9586846
TI  - Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268).
AB  - In the present study a short (120 min) and long-lasting (360 min) antagonism of
      scopolamine-induced amnesia in rats was investigated in an eight-arm radial maze,
      by (3a S, 8a R)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-o
      l[8-(cis2,6-dimethyl-morpholin-4-yl)octyl]-carbamate L-bitartrate hydrate
      (MF268), a new cholinesterase inhibitor. Upon completing the training session,
      the rats were orally administered increasing doses of MF268 (2, 3, 6, 7, and 8
      mg/kg) 60 min prior to s.c. injection of scopolamine (0.25 mg/kg). Following a
      further 60 min the rat was placed in the maze. The reversal of scopolamine
      induced impairment was characterized by an inverted U-shaped dose-response curve.
      A significant reduction in the number of errors, and time taken to complete the
      maze was observed with a dose of 6 mg/kg. The compound improved memory retention
      without affecting scopolamine-induced hypermotility. When the same dose was
      administered 360 min prior to the test a significant reduction in the number of
      amnesic animals was observed, whereas no cognitive improvement was detected when
      either 1-Benzil-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine
      hydrochloride (E2020) (0.25 mg/kg) or tacrine (0.5 mg/kg) were administered 360
      min prior to the test. The kinetics of whole-brain cholinesterase confirmed the
      long-lasting activity for MF268. A clinical relevance for the use of MF268 in AD
      treatment is suggested.

PMID- 9586847
TI  - Effects of the muscarinic antagonists atropine and pirenzepine on olfactory
      conditioning in the honeybee.
AB  - One-trial conditioning of the proboscis extension reflex (PER) in honeybees was
      used to examine the qualitative effects of two muscarinic antagonists, atropine
      and pirenzepine, on the acquisition and retrieval of memory following
      intracranial injection. The main result of this study is that atropine, at a
      relatively high concentration of 10(-2) M, impairs memory retrieval but not
      acquisition of memory after a single olfactory conditioning trial (at this
      concentration, there is no effect of atropine on the sensorimotor components of
      the PER). This result is in agreement with the effects of scopolamine, reported
      in a previously published article. Pirenzepine, at the same concentration as
      atropine, had no effect on either acquisition or retrieval of memory. These
      results suggest that blockade of muscarinic-like receptors, except those that
      bind to pirenzepine, induces solely an impairment of memory retrieval.

PMID- 9586851
TI  - An anxiolytic-like effect of ondansetron disappears in oxazepam-tolerant rats.
AB  - In our experiments a drug from the group of 5-HT3 antagonists--ondansetron (OND)-
      has been used in rats developing tolerance to oxazepam (OXZ). After 7 days of
      oxazepam administration (5 mg/kg i.p.) a significant decrease in the anxiolytic
      behavior was observed in the Crawley test. In the rats already partly tolerant to
      oxazepam, an undiminished anxiolytic-like effect of ondansetron (single injection
      of 0.1 mg/kg i.p., seventh day) was observed. After 14 days of oxazepam
      administration its anxiolytic activity was even more diminished. A single
      injection of ondansetron 0.1 mg/kg restored the anxiolytic behavior: rise of BWT
      (black-white transition) and WSE (white square entrance). After 21 days the
      anxiolytic activity of oxazepam was totally abolished and the single injection of
      ondansetron did not restore the state of anxiolysis. The results show that the
      anxiolytic effects of ondansetron were not influenced in the first stages of
      tolerance development to oxazepam, but the drug was not able to produce an
      anxiolytic effect in the state of full tolerance to oxazepam (after 3 weeks).

PMID- 9586850
TI  - Benzodiazepine dependence: from neural circuits to gene expression.
AB  - The neural mechanisms underlying benzodiazepine dependence remain equivocal. The
      present studies tested the hypothesis that similar neural systems are recruited
      during diazepam tolerance and withdrawal, and that these are associated with
      changes in GABA(A) receptor properties. 2-Deoxyglucose quantitative
      autoradiography was employed to map the brain structures affected during chronic
      treatment and withdrawal from diazepam (5 mg/kg i.p. daily) in rats. Acute
      administration of diazepam evoked widespread reductions in local rates of
      cerebral glucose (LCGU) utilization throughout the brain. Brain structures
      associated with sensory processing developed tolerance to these depressant
      effects of diazepam after 3 days of treatment, whereas tolerance occurred in the
      Papez circuit of emotion after 28 days of treatment. These data suggest that
      adaptive changes in different neuroanatomical circuits may underlie tolerance to
      the various effects of diazepam. During flumazenil-precipitated withdrawal from
      diazepam there were marked increases in glucose use in structures of the Papez
      circuit, the nucleus accumbens, and the basolateral amygdala. These data suggest
      that the Papez circuit features strongly in diazepam tolerance and withdrawal and
      supports a common adaptive process being involved in these phenomena. While GABA
      enhancement of benzodiazepine binding was reduced in the nucleus accumbens after
      repeated diazepam treatment, there was little evidence to support adaptive
      changes in GABA(A) receptors or GABA(A) subunit gene expression (gamma2, alpha1,
      or alpha4) as underlying the functional changes in the identified circuits.
      Alternative neurochemical mechanisms, such as changes in glutamatergic function
      should be considered.

PMID- 9586853
TI  - A study of the duration of acute tolerance induced with hexobarbital in male
      rats.
AB  - Male rats were infused i.v. with hexobarbital to obtain a burst suppression of 1
      s or more in the EEG (SS). At SS the rats were killed and the concentration of
      hexobarbital was determined by HPLC in three parts of the brain. Acute tolerance
      (induced by a 1-h exposure at the SS level) was recorded as an approximately 20%
      increase in brain concentrations of hexobarbital at the last SS during the
      exposure when compared with concentrations recorded at the first SS in the
      controls. Increased brain concentrations (approximately 8%) at SS were recorded
      24 h after induction of acute tolerance. After 48 h the increase was uncertain.
      Thus, acute tolerance to hexobarbital could have cumulative properties if new
      exposures are imposed after 24 h.

PMID- 9586849
TI  - Effects of alcohol, zolpidem, and some other sedatives and hypnotics on human
      performance and memory.
AB  - Zolpidem (Zol), an omega1-agonist, acts via GABA(A) receptors but may differ
      qualitatively from diazepam (Dz) and other benzodiazepines (BZDs). We conducted a
      placebo-controlled, randomized, double-blind, and crossover study to compare the
      psychomotor and cognitive effects of 15 mg Zol with those of 15 mg Dz, 30 mg
      oxazepam (Ox), 7.5 mg zopiclone (Zop), and ethanol (EOH; 0.65 + 0.35 g x kg(-1))
      given to 12 subjects at 1-week intervals. Psychomotor tests (symbol digit
      substitution, simulated driving, flicker fusion, body sway) were done before and
      1, 3.5, and 5 h after intake; immediate and delayed memory were measured between
      1.5 and 3.5 h. The plasma concentrations of drugs were measured by gas
      chromatography and by radioreceptor assay (RRA). The mean values of EOH in blood
      at 1.5, 4, and 5.5 h were 0.82, 0.88, and 0.6 g x l(-1), and the mean values of
      RRA-assayed plasma Dz were 470, 330, and 210 microg x l(-1), respectively. The
      corresponding values of other hypnosedatives, in Dz equivalents (microg x l(-1)),
      were 550, 750, and 330 for Ox; 350, 270, and 70 for Zol; and 160, 210, and 70 for
      Zop. The standard RRA graph for Zol was significantly flatter than those for
      other hypnotics. Zol impaired coordinative, reactive, and cognitive skills at 1
      and 3.5 h more clearly than the other agents did, the most sensitive performance
      (tracking) still being impaired by Zol at 5 h. Dz and Zop were less active than
      Zol objectively; subjective sedation after Dz and Zol was stronger than after
      Zop. Compared to placebo, all active agents tended to impair learning and memory,
      their decremental effects, in declining order, being Zol, Dz > EOH, Ox > Zop.
      During the delay, Dz and Zol caused similar losses of material that had been
      learned. When separating "true" delayed memory from immediate memory (attention
      important), Dz and Zol had equieffects on delayed memory and were more
      detrimental than Zop. When contrasting that against the impaired psychomotor
      performances, it is possible that 15 mg Zol impairs memory relatively less than
      15 mg Dz does.

PMID- 9586848
TI  - Does the sedation resulting from sleep deprivation and lorazepam cause similar
      cognitive deficits?
AB  - It is notoriously difficult to assess the contribution of the sedative effects of
      benzodiazepines to the cognitive impairments that they produce. The purpose of
      the present experiment was to determine whether a similar pattern of cognitive
      impairment would be seen in conditions when subjects felt equally sleepy as the
      result of sleep deprivation. The effects of a sedative dose of lorazepam (2.5 mg)
      in healthy volunteers was therefore compared with the effects of acute sleep
      deprivation (a night on-call) in a group of junior doctors and the effects of
      chronically disturbed sleep due to snoring. Lorazepam, acute sleep deprivation,
      and chronic sleep disturbance all significantly increased subjective sedation. In
      addition, lorazepam significantly impaired performance in two tests of
      psychomotor speed and caused significant anterograde amnesia. Semantic and short
      term memory were not impaired by lorazepam, nor was there any impairment in
      executive function. The only deficit found following acute sleep deprivation was
      in a test of semantic memory, generating examples from a difficult category. The
      only significant deficit in the group suffering from chronically disturbed sleep,
      compared with age-matched controls, was in executive function, and there was a
      nearly significant impairment in sustained attention. These results suggest that,
      despite the common factor of increased subjective sedation, the profile of
      cognitive impairment in the two sleep deprivation groups are neither similar to
      each other nor to that seen following an acute dose of lorazepam.

PMID- 9586852
TI  - Sarmazenil-precipitated withdrawal: a reliable method for assessing dependence
      liability of benzodiazepine receptor ligands.
AB  - The benzodiazepine receptor partial inverse agonist sarmazenil exhibits in vivo
      proconvulsive, but not convulsant, effects in different paradigms in rodents.
      Intravenous sarmazenil challenge given at several fixed intervals following the
      termination of repeated treatment with a markedly sedative dose of diazepam in
      squirrel monkeys was effective in precipitating withdrawal signs, but had no
      comparable effects in vehicle-treated controls. The precipitated withdrawal
      reaction was not only robust, but it was consistently observed in all of the
      diazepam-treated monkeys. Thus, the use of sarmazenil challenge in the
      precipitated withdrawal paradigm provides a reliable method for assessing the
      development of physical dependence during repeated treatment with benzodiazepine
      receptor agonists.

PMID- 9586854
TI  - The influence of alcoholism and cirrhosis on benzodiazepine receptor function.
AB  - In a previous study we reported that the affinity of the platelet benzodiazepine
      receptor was greater in alcoholic cirrhotic patients compared with normal
      controls and that there were detectable ligands for the neuronal benzodiazepine
      receptor in plasma from both alcoholic and nonalcoholic cirrhotic patients. The
      aim of the present study was to assess the separate contributions of alcoholism
      and cirrhosis to the presence of ligands in plasma for the neuronal and
      peripheral benzodiazepine receptors and to changes in peripheral benzodiazepine
      receptor binding in platelets. These parameters were measured in 10 alcoholic
      cirrhotics, 9 nonalcoholic cirrhotics, 7 alcoholics with a normal liver function,
      and 15 nonalcoholic subjects and normal liver function. Both groups of alcoholics
      had been abstinent for several months and the nonalcoholic groups had abstained
      for 24 h before the study. The concentration of ligands for the peripheral
      benzodiazepine receptor were significantly higher in both cirrhotic groups
      compared with the other two groups, suggesting that cirrhosis was responsible for
      this accumulation. Furthermore, the cirrhotic patients with detectable
      concentrations of these ligands had significantly poorer episodic memory than
      those without ligands. However, the presence of ligands for the peripheral
      benzodiazepine receptor did not correlate with the change in receptor affinity,
      which was increased in the alcoholic cirrhotic group compared with all other
      groups. Neither cirrhosis nor alcoholism altered the peripheral benzodiazepine
      receptor number. The cirrhotic patients with detectable ligands for the neuronal
      benzodiazepine receptor showed psychomotor slowing and executive dysfunction. The
      results suggest that the ligands for the peripheral benzodiazepine receptor may
      contribute to some of the cognitive deficits seen in hepatic encephalopathy, but
      are not responsible for the receptor affinity change seen in the alcoholic
      cirrhotics. This affinity change is not solely due to the effects of alcohol and
      could possibly serve as a marker for those at risk for developing alcoholic
      cirrhosis.

PMID- 9586856
TI  - Effect of naloxone on behavioral changes induced by subchronic administration of
      ethanol in rats.
AB  - Endogenous opioid peptides appear to be involved in acute behavioral effects
      induced by single doses of ethanol. However, its role in repeated ethanol
      exposure has not been studied. In the present study ethanol was given to rats at
      the doses of 2 and 4 g/kg by a stomach gauge for 15 days, and its effects on
      spontaneous motility, open-field activity, and active avoidance behavior recorded
      on the 3rd, the 6th and the 15th days. Then the effect of naloxone (0.5 and 2
      mg/kg by intraperitoneal route) was tested against a challenge ethanol dose,
      administrated by oral route, on the 16th day. Control animals received tap water
      and saline instead of ethanol or naloxone, respectively. Both doses of ethanol
      induced a decrease in spontaneous motility that was antagonized by naloxone. Open
      field ambulations were increased by the high dose of ethanol, low-dose lacking
      effect; naloxone did not modify these ethanol effects. The low dose of ethanol
      shortened latency time in shuttlebox, the high dose causing escape and freezing
      responses; none of these effects were modified by naloxone. Therefore, endogenous
      opioid peptides appear to play a limited role in the chronic effects of ethanol
      in rats; particularly its effects in tests inducing an increase in the level of
      anxiety were resistant to naloxone.

PMID- 9586855
TI  - Effects of muscimol or homotaurine on sleep-wake states in alcohol-dependent rats
      during withdrawal.
AB  - Sleep-wake states were studied following withdrawal in 36 adult male wistar
      alcohol-dependent rats, after chronic administration of ethanol (10 g/kg/24 h)
      for 13 days. In the light phase of the withdrawal day, 12 alcohol-dependent rats
      received muscimol (0.25 mg/kg), 12 received homotaurine (140 mg/kg), and 12
      received 0.9% physiological saline (10 ml/kg). The results have been compared
      with a control group of 36 rats that received water during the treatment phase of
      the experiment, and the 14th day received intraperitoneal muscimol or
      homotaurine. Muscimol significantly improves the alterations of sleep-wake states
      in alcohol-withdrawn rats, decreasing the percentage of active wakefulness and
      increasing the percentage of REMS, but without any action on the latency of
      appearance of REMS, which remains shortened. The effects of homotaurine are less
      important on the wakefulness, but it also increases the percentage of REMS
      without influencing its latency of appearance. The influence of these GABA(A)
      agonists is not identical during the whole period of survey in the light phase,
      as there are important differences in the temporal sequences for each of them. We
      conclude that the stimulation of GABA(A) receptors, of which the activity is
      decreased during alcohol withdrawal, significantly improves the disturbances in
      the sleep-wake states in the alcohol-dependent rats, in a time-related manner,
      and there are significant pharmacodynamic differences between muscimol and
      homotaurine.

PMID- 9586857
TI  - CCK(B) antagonists protect against some aspects of the ethanol withdrawal
      syndrome.
AB  - Effects of the CCK(B) antagonists, CAM1028 and C1988, and the CCK(A) antagonist,
      CAM1481, were studied on the ethanol withdrawal syndrome. When handling-induced
      behavior was measured hourly for 12 h from withdrawal of ethanol, a small, but
      significant, protective effect was seen with 3 mg/kg CAM1028, but not with 0.3,
      1, or 10 mg/kg. C1988 (0.3 1,3, or 10 mg/kg), or CAM1481 (0.1 or 1 mg/kg), had no
      effects. At 16 h from ethanol withdrawal, these ratings were significantly
      decreased by 3 mg/kg CAM1028 or C1988, but not by lower doses. At 16 h, CAM1481
      had very small, but significant, protective effects. At 3 mg/kg, CAM1028,
      increased the latencies to audiogenic seizures, but had only small effects on
      convulsion incidence. CAM1481 did not alter the audiogenic convulsions. The
      decrease in convulsion thresholds to NMDLA, at 16 h from ethanol withdrawal, was
      completely prevented by CAM1028 or C1988, at 1 and at 3 mg/kg, but not by lower
      doses; CAM1481 had no significant effects. The results suggest change in CCK(B)
      receptors may be involved in the later stages of the ethanol withdrawal syndrome.

PMID- 9586858
TI  - Prior repeated exposure to a 5-HT3 receptor agonist does not alter the ethanol
      induced conditioned taste aversion in rats.
AB  - Several reports have indicated that the brain serotonergic 5-HT3 receptors are
      involved in at least some central effects of ethanol in rats. However, using an
      operant drug discrimination procedure, we have shown that these receptors are not
      primarily involved in the discriminative stimulus effects of ethanol. The aim of
      the present study was to further elucidate the role of 5-HT3 receptors in the
      formation of the ethanol-cueing effects in rats. To this purpose, a
      crossfamiliarization conditioned taste aversion (CF-CTA) procedure was used. Four
      daily injections of 1.5 g/kg ethanol (10% v/v) resulted in a significant
      attenuation of the subsequent ethanol-induced CTA. In contrast, four daily
      injections of the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (mCPBG; 50
      microg per rat, i.c.v.) did not alter the subsequent ethanol-induced CTA. The 50
      microg dose of mCPBG produced a marked CTA in a control experiment. These results
      taken together with some previous findings from our laboratory suggest that the
      brain 5-HT3 receptors do not play any crucial role in the mediation of the
      discriminative stimulus effects of ethanol.

PMID- 9586859
TI  - Ethanol, stroke, brain damage, and excitotoxicity.
AB  - The N-methyl-d-aspartate (NMDA)-glutamate receptor could contribute to stroke,
      trauma, and alcohol-induced brain damage through activation of nitric oxide
      formation and excitotoxicity. In rat primary cortical cultures NMDA was more
      potent at activating nitric oxide formation than triggering excitotoxicity.
      Ethanol dose dependently inhibited both responses. In contrast, treatment of
      neuronal cultures with ethanol (100 mM) for 4 days significantly increased NMDA
      stimulated nitric oxide formation and excitotoxicity. These findings suggest that
      ethanol acutely inhibits but chronically causes supersensitivity to NMDA-induced
      excitotoxicity in neuronal cultures. To investigate ethanol's interaction with
      stroke induced damage models of global cerebral ischemia were studied. Transient
      global ischemia resulted in a loss of hippocampal CA1 pyramidal neurons over a 3-
      to 5-day period. Determinations of the NMDA receptor ligand binding stoichiometry
      or postischemic receptor binding changes did not show differences between neurons
      that undergo delayed neuronal death following ischemia and those that show no
      toxicity, for example, CA1 and dentate gyrus, respectively. Acute ethanol (3
      g/kg) was found to protect against ischemia-induced CA1 hippocampal damage by
      lowering body temperature, but not under temperature controled conditions. These
      studies indicate that the factors contributing to stroke-induced brain damage are
      complex, although they are consistent with chronic ethanol increasing stroke
      induced brain damage by increasing NMDA excitotoxicity.

PMID- 9586860
TI  - Analgesia and abuse potential: an accidental association or a common substrate?
AB  - The fact that centrally acting analgesics have abuse potential commensurate with
      their analgesic activity raises the question of whether these effects are
      related. The abuse potential of drugs depends on their ability to produce
      reinforcing effects, which are mediated by a neural system that includes the
      ventral tegmental dopamine cells and their connections with the ventral striatum.
      Morphine and amphetamine are both powerful analgesics and have high abuse
      potential. Their analgesic and reinforcing effects are mediated by similar
      receptors, similar sites of action, and overlapping neural substrates. These
      coincidences suggest that reinforcers may produce analgesia by transforming the
      aversive affective state evoked by pain into a more positive affective state. The
      implications of this hypothesis and its relation to other known mechanisms of
      analgesia are discussed. The hypothesis predicts that drugs with reinforcing
      effects should produce analgesia. A survey of drugs acting through 21 classes of
      receptors reveals that in 13 classes there is evidence for both analgesic and
      reinforcing effects that are approximately equipotent. The GABA(A) agonists were
      found to be the only drugs with confirmed abuse potential that lack analgesic
      activity. The interpretation of this and several other anomalous cases is
      discussed.

PMID- 9586861
TI  - The acute effects of amphetamine derivatives on extracellular serotonin and
      dopamine levels in rat nucleus accumbens.
AB  - The acute effects of amphetamine derivatives on extracellular concentration of
      serotonin (5-HT) and dopamine in the nucleus accumbens were studied with in vivo
      microdialysis using conscious, freely moving rats. 5-HT, dopamine, and their
      major metabolites were measured by HPLC with electrochemical detection.
      Amphetamine (1.0-9.0 mg/kg) elevated dopamine levels considerably, but failed to
      affect the levels of 5-HT, except at the highest dose administered. 3,4
      Methylenedioxyamphetamine (MDA, 1.0-9.0 mg/kg) and 3,4
      methylenedioxymethamphetamine (MDMA, 1.0-9.0 mg/kg) elevated both 5-HT and
      dopamine levels dose dependently. The failure of 2,5-dimethoxy-4
      methylamphetamine (DOM, 0.5-1.0 mg/kg) to affect the 5-HT levels suggests that
      extracellular levels of 5-HT play a minor role in hallucinogenic activity. The
      strong effects of MDA and MDMA on levels of 5-HT indicate that their actions on
      serotonergic mechanisms are different from those of the hallucinogens. In
      addition, methylenedioxyamphetamines may act via dopaminergic mechanisms similar
      to those of amphetamine.

PMID- 9586862
TI  - Evaluation of unconditioned novelty-seeking and d-amphetamine-conditioned
      motivation in mice.
AB  - Following repeated association between psychostimulant drugs and a distinct
      environment, contextual cues acquire the ability to elicit a conditioned approach
      response. Further, both rats and mice have a natural drive to seek for the
      experience of novelty, and a previously unknown environment is able to elicit an
      unconditioned approach response. Both the experience of novelty and amphetamine
      (AMPH)-conditioned effects have been associated in rodents with the activation of
      brain meso-limbic dopaminergic pathways. This study assessed the relative
      strength of AMPH-conditioned and novelty-induced unconditioned motivations in
      mice. During the pretreatment period, mice were randomly assigned to three
      different treatment history groups, and received d-AMPH (0, 2, or 10 mg/kg i.p.
      once/day) injections for 3 days in the presence of a familiar environment.
      Following a 48-h washout from the last drug injection, animals were placed in the
      familiar and pretreatment-paired environment and challenged with either SAL (to
      evaluate conditioning) or a standard AMPH dose (2 mg/kg, to assess either acute
      drug effects or carryover influences of each animal's treatment history with the
      same drug). Following the opening of a partition, animals showed both a clear-cut
      preference for a novel environment as well as a marked novelty-induced
      hyperactivity. Interestingly, when mice were tested in a drug-free state in this
      free-choice paradigm, they expressed neither conditioning to the drug-associated
      environment nor carry-over effects on the novelty-induced hyperactivity profile.
      On the other hand, mice injected with AMPH showed a mixed profile, with AMPH 2
      treatment history mice showing a conditioned preference for the familiar and drug
      paired environment, whereas AMPH 10 animals preferred to spend more time in the
      novel compartment. Both AMPH doses were associated with an increased locomotion,
      whereas only the AMPH 10 dose resulted in a stereotyped behavioral syndrome,
      possibly reminiscent of an aversive "poor welfare" condition. Thus, as a function
      of the drug dosage, differential positive or negative incentive properties are
      suggested to be evoked by the AMPH-conditioned environment. In conclusion, a
      reliable and useful experimental paradigm has been developed to investigate the
      issue of vulnerability to a variety of habit-forming agents or emotional
      experiences whose positive reinforcing properties may rely on a common
      neurobiological mechanism.

PMID- 9586863
TI  - Sensitization of the mesoaccumbens dopamine response to nicotine.
AB  - This article reviews the evidence that pretreatment with nicotine causes a
      regionally selective sensitization of its stimulatory effects on a pathway, the
      mesoaccumbens dopamine (DA) system, which has been implicated in the locomotor
      stimulant response to nicotine and its ability to reinforce self-administration.
      The sensitization evoked by daily injections of nicotine is associated with a
      regionally selective downregulation of the control of mesoaccumbens DA neurons by
      inhibitory autoreceptors and depends upon co-stimulation of NMDA glutamatergic
      receptors. It is suggested that the sensitization is related to enhanced burst
      firing of mesoaccumbens neurons, which results in an enhancement of DA release
      into the extracellular space between the cells where it acts upon putative
      extrasynaptic dopamine receptors. The studies with NMDA receptor antagonists
      revealed a dissociation between the expression of sensitized mesoaccumbens DA and
      locomotor responses to nicotine. It is proposed, therefore, that the sensitized
      mesoaccumbens DA responses to nicotine may be implicated in psychopharmacological
      responses to drug concerned more closely with nicotine dependence.

PMID- 9586864
TI  - Dependence on smoking and the acoustic startle response in healthy smokers.
AB  - Recent data from nicotine-dependent rats (14) and healthy smokers (18) would
      suggest that nicotine withdrawal modulates the acoustic startle reflex in a way
      similar to that of fear (5,20). We examined this directly using nonsmokers and
      healthy smokers who had no deprivation, brief deprivation (2-3 h), or prolonged
      deprivation (15 h). Groups differences in heart rate (HR), alveolar carbon
      monoxide (CO) levels, and desire and craving for cigarettes confirmed the
      presence of smoking withdrawal. However, there were no significant differences in
      the magnitude of the baseline startle response among the differently deprived
      smokers or between the smokers and the nonsmokers. Subsequent startle tests were
      carried out in the smokers during repeated sequences of preparing a cigarette for
      smoking (smoking cues) and then smoking. Whereas we did find statistically
      significant interactions of smoking deprivation with smoking cues and with
      renewed smoking, there was only weak confirmation of a priori predictions of
      motivational effects of smoking cues or of smoking. We conclude that smoking
      dependence may not affect the acoustic startle response itself; modulation seems
      to occur, but only after experience with the test situation. Discussed were
      possible mechanisms of this modulation in both humans and animals and further
      application of the startle response for providing interdisciplinary assessments
      of the motivational effects of nicotine withdrawal.

PMID- 9586865
TI  - Regular caffeine consumption: a balance of adverse and beneficial effects for
      mood and psychomotor performance.
AB  - It has often been pointed out that caffeine is the most widely "used"
      psychoactive substance in the world, and accordingly, there is a very large
      amount of research available on the effects of caffeine on body and mind. In
      particular, a psychostimulant action of caffeine is generally accepted as well
      established; for example, caffeine has been found to quicken reaction time and
      enhance vigilance performance, and to increase self-rated alertness and improve
      mood. There is, however, a real difficulty in determining the net effects of
      caffeine. In a typical experiment the subjects have a history of regular caffeine
      consumption, and they are tested on caffeine and a placebo after a period of
      caffeine deprivation (often overnight). The problem with relying solely on this
      approach is that it leaves open the question as to whether the results obtained
      are due to beneficial effects of caffeine or to deleterious effects of caffeine
      deprivation. The present article briefly reviews this evidence on the
      psychostimulant effects of caffeine, and presents some new data testing the
      hypothesis that caffeine may enhance cognitive performance to a greater extent in
      older adults than in young adults. No age-related differences in the effects of
      caffeine on psychomotor performance were found. We conclude that overall there is
      little unequivocal evidence to show that regular caffeine use is likely to
      substantially benefit mood or performance. Indeed, one of the significant factors
      motivating caffeine consumption appears to be "withdrawal relief."

PMID- 9586866
TI  - Cocaine sensitivity in Borna disease virus-infected rats.
AB  - Borna disease virus (BDV) is a neurotropic RNA virus that infects warm-blooded
      animals to cause disturbances of movement and behavior. Studies in infected rats
      have demonstrated behavioral sensitivity to direct and indirect dopamine (DA)
      agonists; however, behavioral responses to an indirect DA agonist with a pure
      presynaptic effect have not been analyzed. Rats infected with BDV had an enhanced
      response to the locomotor, behavioral, and convulsant effects of cocaine at
      intraperitoneal doses of 7.5, 15, and 30 mg/kg. The basis for this sensitivity
      was examined by striatal DA uptake site and D1 and D2 receptor autoradiography.
      DA uptake sites, labeled with [3H] mazindol, were reduced in medial caudate
      putamen (CP), and binding of [3H] raclopride to D2 sites was reduced in medial
      and ventral striatal areas. The topography of DA uptake and D2 site loss
      corresponds to the distribution of BDV viral nucleic acids in CP and overlays the
      medial striatal areas that function in conditioned reward. The BDV-infected rat
      provides a model of cocaine sensitivity based on viral central nervous system
      infection and may have relevance for studies of cocaine abuse in the context of
      other viral encephalopathies, such as those associated with HIV infection.

PMID- 9586867
TI  - Enhancement of latent inhibition in the rat by the CCK antagonist proglumide.
AB  - The behavioral paradigm of latent inhibition (LI) involves the retardation of
      conditioning to a stimulus when paired with reinforcement, if preexposure to that
      stimulus with no significant consequence has occurred. This phenomenon is
      believed to reflect a process of learning to ignore stimuli as irrelevant.
      Disruption in LI can be considered to be an attentional deficit observed in
      schizophrenia. The neuropeptide cholecystokinin (CCK), which coexists with
      dopamine (DA) in some brain regions, has been implicated in the pathophysiology
      of schizophrenia. The present study examined the effects of the nonselective CCK
      antagonist proglumide on LI (0.25, 0.5, and 1.0 mg/kg) using a conditioned
      suppression of drinking procedure in rats. For purposes of comparison the effects
      of haloperidol (0.1 mg/kg) were also investigated. Administration of 1.0 and 0.5
      mg/kg, but not 0.25 mg/kg, proglumide was found to reduce suppression of drinking
      behavior in animals preexposed (PE) to a flashing light stimulus. These animals
      developed LI under conditions where preexposed control animals exhibited
      suppression of drinking behavior similar to that of nonpreexposed (NPE) control
      animals. These findings for proglumide were comparable to the effects on drinking
      behavior of 0.1 mg/kg haloperidol. The enhancement of LI by proglumide may be
      interpreted in terms of CCK dopamine interactions. Because CCK may modulate
      dopamine, the results reported here for proglumide strengthen the argument for
      the investigation of CCK-based drugs as potential antipsychotic agents.

PMID- 9586868
TI  - Subchronic physostigmine pretreatment in guinea pigs: effective against soman and
      without side effects.
AB  - The behavioral and neurophysiological effects of the subchronically administered
      cholinesterase-inhibitor physostigmine (PHY) (0.025 mg/kg/h) either with or
      without the muscarinergic antagonist scopolamine (SCO) (0.018 mg/kg/h) were
      determined in guinea pigs. In contrast to a single injection of PHY, subchronic
      application by osmotic minipumps of PHY, even without SCO, caused no behavioral
      or neurophysiological side effects. Also, the efficacy of such a pretreatment in
      counteracting soman-induced lethality and apparent symptoms of intoxication were
      determined. After subchronically administered PHY or PHY + SCO, the treated
      animals were protected against a 3 x LD50 dose of soman.

PMID- 9586872
TI  - Inherited breast cancer: increasingly familiar territory.

PMID- 9586869
TI  - Effects of various drugs including organophosphorus compounds (OPC) and
      therapeutic compounds against OPC on DRL responding.
AB  - The effects of various drugs were assessed in rats responding under a
      Differential-Reinforcement-of-Low-Rate 30-s (DRL 30-s) schedule. Atropine,
      scopolamine, and CEB-1957 (a new muscarinic blocker) increased response rate and
      decreased reinforcement rate, while methylatropine only decreased reinforcement
      rate. Physostigmine decreased response and reinforcement rates, when
      pyridostigmine had few effect on DRL responding. The irreversible
      acetylcholinesterase (AChE) inhibitors organophosphorus compounds (OPC) soman and
      sarin, injected at one-third of the LD50 did not consistently alter DRL
      performance, suggesting that they produce few behavioral effects in the rat when
      administered at subtoxic doses. Three oximes--pralidoxime, pyrimidoxime, and HI-6
      -decreased both response and reinforcement rates. Mecamylamine had few consistent
      effects on performance, and nicotine, d-amphetamine, diazepam, and the wakening
      drug modafinil increased response rate and decreased reinforcement rate. These
      two latter drugs also increased the number of very premature responses. These
      results, taken together, indicate that a DRL schedule is a useful tool to bring
      to light the existence of psychotropic effects of a drug. The explanation of drug
      induced alterations of DRL performance, in terms of effects on cognition or on
      mood, is also discussed.

PMID- 9586871
TI  - Behavioral effects of NBQX, a competitive antagonist of the AMPA receptors.
AB  - NBQX, a specific and potent AMPA receptor antagonist has been found to be
      neuroprotective in various models of ischemia and to have anticonvulsant
      properties in different models of epilepsy. In this experiment, the
      neurobehavioral effects of NBQX were studied. In an open field, an important
      ataxia was emphasized at a dose of 60 mg/kg. In a swimming task, an increase of
      the escape latencies was noted on the third day at a dose of 40 mg/kg. In a
      Morris water maze task, doses devoid of effects on locomotion were used (10, 20,
      and 30 mg/kg). There was no effect on the acquisition of the task at 10 mg/kg and
      a slight impairment at 20 mg/kg, but the rats did not learn the task at 30 mg/kg.
      This impairment was reversible, as shown by the increasing performance of this
      group without treatment. No impairment was noted in the retention phase of the
      Morris water maze task. The results are discussed relative to the role of the
      AMPA receptor in memory processes.

PMID- 9586870
TI  - Biochemical and behavioral deficits in adult rat following chronic dichlorvos
      exposure.
AB  - The present study was carried out to assess the biochemical and behavioral
      sequelae of chronic dichlorvos (6 mg/kg b.wt/day for 8 weeks) exposure in rats.
      Dichlorvos administration significantly decreased the activities of neuropathy
      target esterase and other carboxylesterase viz., paraoxon resistant and mipafox
      and paraoxon resistant esterases. The acetylcholinesterase activity was also
      appreciably decreased following dichlorvos exposure. The alterations in
      biochemical parameters were also reflected in the behavioral patterns of
      dichlorvos-treated animals. Dichlorvos administration caused a marked decrease in
      both the ambulatory and stereotypic components of spontaneous locomotor activity
      of rats. The muscle strength and coordination of the dichlorvos-treated animals
      was also significantly impaired. Besides, a marked deterioration in the memory
      function assessed in terms of the conditioned avoidance response was discernible
      at the end of the treatment schedule in the experimental animals.

PMID- 9586875
TI  - Radiation therapy and survival in breast cancer patients with 10 or more positive
      axillary lymph nodes treated with mastectomy.
AB  - PURPOSE: Adjuvant loco-regional radiation (XRT) frequently is recommended after
      mastectomy and adjuvant systemic therapy in patients with 10 or more positive
      axillary lymph nodes (ALN) to reduce the high loco-regional failure rate observed
      in this subset. In this study, we explored the possibility that adjuvant loco
      regional radiation therapy (LR-XRT) also could decrease distant failure and
      improve overall survival (OS) in this subset of poor-prognosis patients. PATIENTS
      AND METHODS: Retrospectively, 618 breast patients with 10 or more positive ALN
      were studied. The median follow-up time was 7.5 years. All patients received
      systemic adjuvant therapy and 35% also received adjuvant radiation therapy. Loco
      regional failure, distant failure, and OS analyses were adjusted for age, tumor
      size, number of positive ALN, and estrogen receptor (ER) status using Cox
      regression model. RESULTS: As expected, patients had a very high risk of loco
      regional and distant failure. At 5 years, 30% of patients had loco-regional
      failure as a first event and 54% had distant failure. Radiation dramatically
      reduced loco-regional failure (hazards rate ratios [RR]=0.29; 95% confidence
      interval [CI], 0.19 to 0.45). The adjusted 5-year loco-regional failure rate was
      13% with radiation and 38% without radiation (P=.0001). Radiation also was
      associated with improved distant control (RR=0.75; 95% CI, 0.58 to 0.96). The
      adjusted 5-year distant failure rate was 48% with radiation and 58% without
      radiation (P=.02). OS also improved with radiation (RR=0.68; 95% CI, 0.53 to
      0.85). The adjusted 5-year OS was 56% with radiation and 42% without radiation
      (P=.001). CONCLUSION: In this cohort of high-risk breast cancer patients, XRT was
      associated with less loco-regional and distant failure and improved OS. This
      suggests that improved loco-regional control might decrease secondary systemic
      spread and improve survival.

PMID- 9586873
TI  - BRCA-associated breast cancer in young women.
AB  - PURPOSE: To delineate the clinical characteristics and outcomes of breast cancer
      that arises in the setting of a germline BRCA mutation and to compare BRCA
      associated breast cancers (BABC) with those that arise in women without
      mutations. PATIENTS AND METHODS: We reviewed the clinical records of 91 Ashkenazi
      Jewish women ascertained during studies of the genetics of early-onset breast
      cancer. All women underwent testing for the BRCA1 mutations 185delAG and
      5382insC. After the discovery of BRCA2, 79 women were also tested for the BRCA2
      mutation 6174delT. RESULTS: Mutations were identified in 30 women (33%). BABC
      were less likely to present with stage I disease than cases in women without
      mutations (27% v 46%), more likely to have axillary nodal involvement (54% v46%),
      and more likely to have extensive axillary involvement (25% v 17%). These
      differences were not statistically significant. BABC were significantly more
      likely to be histologic grade III (100% v 59%, P=.04) and to be estrogen receptor
      negative (70% v 34%, P=.04). In the entire cohort, there were no significant
      differences between BABC and non-BRCA-associated cancers in 5-year relapse-free
      survival (65% v 69%, P=not significant [NS]), 5-year event-free survival (57% v
      68%, P=NS), or 5-year overall survival. However, among cases diagnosed within 2
      years of study entry, there was a trend toward shorter event-free survival in
      BRCA heterozygotes, but not relapse-free survival. Women with germline BRCA
      mutations were significantly more likely to develop contralateral breast cancer
      at 5 years (31% v 4%, P=.0007). CONCLUSION: BABC present with adverse clinical
      and histopathologic features when compared with cases not associated with BRCA
      mutations. However, the prognosis of BABC appears to be similar to that of
      nonassociated cancer. Further studies of incident cases are necessary to define
      the independent prognostic significance of germline BRCA mutations.

PMID- 9586876
TI  - High-dose chemotherapy with autologous hematopoietic progenitor-cell support as
      part of combined modality therapy in patients with inflammatory breast cancer.
AB  - PURPOSE: To evaluate the feasibility of high-dose chemotherapy (HDC) with
      autologous hematopoietic progenitor-cell support (AHPCS) as part of combined
      modality therapy (CMT) in patients with inflammatory breast cancer (IBC).
      PATIENTS AND METHODS: From April 1993 to March 1997, 30 patients with IBC were
      treated at our program. Twenty-three patients received neoadjuvant chemotherapy
      (NAC) before HDC; 18 patients also received adjuvant chemotherapy following
      surgery, but before HDC. All patients received HDC with high-dose
      cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient
      underwent surgery either before (27 patients) or after (three patients) HDC.
      Patients received radiotherapy after HDC in addition to tamoxifen if their tumors
      were estrogen receptor-positive. RESULTS: Thirteen patients experienced grade 3
      or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this
      represented drug-induced lung injury, which in all cases responded to a 10-week
      course of corticosteroids. The only treatment-related death was secondary to
      hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity,
      which was completely reversible. All patients engrafted promptly. Eight patients
      relapsed, five of whom had a poor pathologic response to NAC. Relapses were local
      (five patients), local plus systemic (one), or systemic only (two). Median follow
      up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44)
      months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51%
      to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease
      free survival (DFS) and overall survival have not yet been reached. CONCLUSION:
      HDC as part of CMT is feasible in patients with IBC. The toxicity of this
      treatment program is significant, but tolerable. Despite the short follow-up
      duration, the promising DFS observed in this group of patients warrants
      randomized studies that include a HDC-containing arm in patients with IBC.

PMID- 9586879
TI  - Vascular enumeration as a significant prognosticator for invasive breast
      carcinoma.
AB  - PURPOSE: Vascular enumeration has been claimed to be an independent
      prognosticator for invasive breast cancer. Most of the studies have performed a
      manual count of the vessels. Few investigators have used image analyzers to
      reduce subjectivity in the measures. The aim of this retrospective study was to
      compare the manual vessel count to the counts obtained with an image analyzer and
      to estimate their possible prognostic influence. MATERIALS AND METHODS: We
      selected 112 patients with invasive ductal carcinoma, treated with radical
      mastectomy followed by chemotherapy and with a minimal follow-up time of 60
      months (5 years). After immunostaining with factor VIII, we performed a double
      count of the vessels. First, we performed a manual count following Gasparini's
      criteria, and second, we used an image analyzer (Microm, Barcelona, Spain) to
      count the vessels in eight adjacent microscopic fields with a 20x objective, to
      reach a total area of 0.98 mm2. The image analyzer calculated the total number of
      vessels, their size and also the percentage of the field occupied by the vessels.
      RESULTS: In our series, vascular enumeration showed no significant association
      with histologic grade (Bloom-Scarff-Richardson grading), tumor size, or staging.
      CONCLUSION: Vascular enumeration with both methods was an independent
      prognosticator for relapse-free-survival (RFS) in both node-negative and 
      positive patients in the univariate analysis, but only vascular enumeration with
      the image analyzer was an independent prognostic factor in the multivariate
      analysis, together with lymph node metastases.

PMID- 9586877
TI  - Eastern Cooperative Oncology Group randomized trials of observation versus
      maintenance therapy for patients with metastatic breast cancer in complete
      remission following induction treatment.
AB  - PURPOSE: To investigate the value of maintenance treatment for patients with
      metastatic breast cancer whose disease is in complete remission (CR). PATIENTS
      AND METHODS: One hundred ninety-five women (141 eligible) whose disease was in CR
      or in CR except for bone metastases following six cycles (6 months) of
      doxorubicin-containing induction treatment were randomized to receive
      cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and
      halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR
      after 24 months of induction treatment were randomized to continue chemotherapy
      for 4 more years or stop chemotherapy. RESULTS: Among patients randomized to
      CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia
      in 3%, cardiac in 2%, and diabetes in 1%. The median time to relapse from
      randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P <
      .0001). The median time to death was 32.2 months on CMF(P)TH and 28.7 months on
      observation (P=.74). Similar results were seen in the pilot study (median time to
      relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too
      small for statistical significance). Maintenance treatment was always the most
      significant covariate in time-to-relapse models. CONCLUSION: There is definite
      toxicity associated with CMF(P)TH maintenance treatment. When CR was obtained on
      induction, maintenance treatment with CMF(P)TH was never significant in survival
      models. However, maintenance treatment was always the most significant covariate
      in the time-to-relapse models, which motivates its consideration for
      appropriately informed patients.

PMID- 9586881
TI  - High-dose induction chemoradiotherapy followed by autologous bone marrow
      transplantation as consolidation therapy in rhabdomyosarcoma, extraosseous
      Ewing's sarcoma, and undifferentiated sarcoma.
AB  - PURPOSE: To improve response and survival rates in patients with high-risk
      rhabdomyosarcoma (RMS), extraosseous Ewing's sarcoma, and undifferentiated
      sarcoma, we used a short course of induction with multi-agent chemotherapy,
      hyperfractionated radiotherapy, and surgery when possible. Consolidation was with
      intensive chemotherapy and autologous bone marrow transplantation (ABMT).
      PATIENTS AND METHODS: Twenty-six patients (21 with RMS, three with
      undifferentiated sarcoma, and two with extraosseous Ewing's sarcoma) were entered
      onto the protocol between June 1990 and March 1994. Induction consisted of
      ifosfamide, etoposide, doxorubicin, dactinomycin, cyclophosphomide, and
      vincristine, and a split course of hyperfractionated radiotherapy. Patients who
      attained a complete response (CR) or good partial response (GPR) received
      consolidation with high-dose melphalan and etoposide followed by ABMT. RESULTS:
      Of 26 previously untreated patients 19 (73%) achieved a CR (n=13) or GPR (n=6) at
      the completion of induction and underwent ABMT. Two-year overall survival (OS)
      was 56% (95% confidence interval [CI], 36% to 76%) and progression-free survival
      (PFS) was 53% for the whole group (95% CI, 33% to 73%). CONCLUSION: Consolidation
      of response by myeloablative chemotherapy was well tolerated. Split-course
      hyperfractionated radiotherapy did not increase the rate of local control. The
      results of this short-course therapy were comparable to previous therapies of 1
      to 2 years' duration. Induction and consolidation chemotherapy, as well as
      radiation dose, could be further intensified, since no death due to toxicity
      occurred among these patients.

PMID- 9586880
TI  - Characteristics and correlates of fatigue after adjuvant chemotherapy for breast
      cancer.
AB  - PURPOSE: Clinical reports suggest that many breast cancer patients experience
      persistent fatigue as a long-term side effect of adjuvant chemotherapy treatment.
      To investigate this issue further, we examined the characteristics and correlates
      of fatigue in women who had completed adjuvant chemotherapy for breast cancer and
      in a comparison group of women with no history of cancer. PATIENTS AND METHODS:
      Participants were 61 women with breast cancer who had completed chemotherapy an
      average of 471 days previously and 59 women with no history of cancer. All
      participants completed standardized self-report measures of fatigue, sleep
      quality, menopausal symptoms, and coping and were administered a structured
      clinical interview to identify current and past psychiatric disorder. RESULTS:
      Compared with women with no history of cancer, former adjuvant chemotherapy
      patients reported more severe fatigue (P < .01) and worse quality of life because
      of fatigue (P < .05). More severe fatigue among patients was significantly (P <
      .05) related to poorer sleep quality, more menopausal symptoms, greater use of
      catastrophizing as a coping strategy, and current presence of a psychiatric
      disorder. CONCLUSION: These findings support the view that many breast cancer
      patients experienced heightened fatigue after completion of adjuvant chemotherapy
      treatment. Results yield a profile of women who are at increased risk for
      heightened fatigue after chemotherapy and suggest ways to intervene clinically to
      prevent or reduce fatigue in this patient population.

PMID- 9586882
TI  - Presence of tumor cells in bone marrow but not in blood is associated with
      adverse prognosis in patients with Ewing's tumor. Societe Francaise d'Oncologie
      Pediatrique.
AB  - PURPOSE: Gene fusions that result from the chromosome translocations observed in
      Ewing's tumor (ET) provide tumor-specific markers that can be used to detect the
      presence of tumor cells in peripheral blood (PB), bone marrow (BM), and stem cell
      collection (SCC). These markers were used to evaluate, at diagnosis, a series of
      67 ET patients. PATIENTS AND METHODS: RNA was extracted from nucleated cells from
      PB and BM and a nested reverse-transcriptase polymerase chain reaction (RT-PCR)
      was performed to search for EWS-FLI-1 or EWS-ERG fusion transcripts that resulted
      from the t(11;22) or t(21;22) translocations, respectively. RESULTS: At
      diagnosis, 16 of 62 (26%) patients had circulating tumor cells. This was not
      correlated with any clinical parameter. In contrast, Ewing's cells were detected
      by RT-PCR in BM in 14 of 43 (33%) patients and were associated with the presence
      of clinically detectable metastases and a statistically significant unfavorable
      outcome in univariate analysis. There was no correlation between the RT-PCR
      results in PB and in BM. CONCLUSION: These results suggested that the monitoring
      of BM but not of PB by RT-PCR might constitute an important criterion for the
      staging, at diagnosis, of patients with ET. Further studies should appreciate the
      relationship or independence of this marker toward other classical prognostic
      factors in ET, particularly to the presence of clinically detectable metastases.

PMID- 9586884
TI  - Neuropsychologic functioning of survivors of childhood medulloblastoma randomized
      to receive conventional or reduced-dose craniospinal irradiation: a Pediatric
      Oncology Group study.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that survivors of
      medulloblastoma who were younger at diagnosis and those who received standard
      dose cranial irradiation (SRT) of 36 Gy would have a lower performance on
      standardized tests of cognitive function and achievement than children who were
      older and those treated with reduced-dose cranial irradiation (RRT) of 23.4 Gy.
      PATIENTS AND METHODS: Eligible patients had been treated on Pediatric Oncology
      Group (POG) study 8631 for low-risk medulloblastoma that randomized patients to
      receive RRT or SRT after surgical resection. Those who were alive and free of
      progressive disease 6.1 to 9.9 years from completion of treatment were eligible
      for this study. Of the 35 eligible patients, 22 patients (13 SRT, nine RRT)
      participated in a battery of tests that included intellectual and academic
      development as well as ratings of health-related quality of life. RESULTS:
      Patients were stratified by treatment group (SRT v RRT) and into younger (Y) and
      older (O) groups by the median age at diagnosis (8.85 years), which resulted in
      four groups that we hypothesized would show neuropsychologic test scores in the
      following order: Y/SRT less than Y/RRT less than O/SRT less than O/RRT. Evidence
      to support the hypothesized ordering of groups in terms of neuropsychologic
      toxicity was obtained with regard to Performance Intelligence Quotient (IQ), Full
      Scale IQ, Attention, Reading, and Arithmetic. CONCLUSION: Children treated for
      medulloblastoma experienced less severe neuropsychologic toxicity when treated
      with 23.4 Gy instead of 36 Gy cranial irradiation. Older children experienced
      less toxicity than children who were younger at the time of irradiation.

PMID- 9586883
TI  - Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an
      association with intermediate-dose intravenous methotrexate and intrathecal
      triple therapy--a Pediatric Oncology Group study.
AB  - PURPOSE: To describe the incidence of acute neurotoxicity (NT) in children with
      lower risk B-precursor acute lymphoid leukemia (ALL) treated with intermediate
      dose methotrexate (MTX) or divided dose oral MTX with or without intravenous
      (i.v.) mercaptopurine (MP) and extended intrathecal triple therapy. PATIENTS AND
      METHODS: Thirteen hundred four patients were entered onto Pediatric Oncology
      Group (POG) 9005, a randomized phase III trial, between January 11, 1991 and
      September 1, 1994. After remission induction, patients were randomized to one of
      three 24-week intensification schedules: regimen A, MTX 1,000 mg/m2 i.v. infused
      over 24 hours and MP 1,000 mg/m2 i.v. infused over 6 hours; regimen B, low-dose
      repetitive MTX 30 mg/m2 orally every 6 hours for six doses and i.v. MP; or
      regimen C, i.v. MTX alone. Intensification was given every 2 weeks for 12
      courses. CNS prophylaxis was age-adjusted intrathecal MTX (ITM). In August 1992,
      the CNS prophylaxis was changed to age-adjusted triple intrathecal therapy (TIT).
      Reports of grades 3 and 4 acute NT were reviewed. RESULTS: Acute NT was reported
      in 95 of 1,218 (7.8%) eligible patients treated on POG 9005. The incidence by
      regimen was regimen A, 46 of 543 patients (8.3%); regimen B, 13 of 354 patients
      (3.7%); and regimen C, 36 of 321 patients (11.2%) (P < .001). The majority of
      events were seizures and the median number of days to first occurrence of
      symptomatic NT after ITM or TIT was 10 to 11 days. Computed tomography (CT) or
      magnetic resonance imaging (MRI) evidence consistent with leukoencephalopathy
      (LE), with or without the presence of cerebral calcifications, was observed in
      75% and 77.1 % of symptomatic patients treated on regimens A and C, respectively,
      but in only 15.4% of symptomatic patients treated on regimen B (P < .001).
      Factors associated with an increased incidence of NT included increased
      cumulative exposure with repeated i.v. MTX (regimens A and C v B), increased MTX
      leucovorin (LCV) ratio (regimens A and C v B), and choice and timing of TIT
      therapy. The use of i.v. MP during intensification did not appear to contribute
      to these complications. The switch to TIT CNS prophylaxis was associated with an
      inferior overall 4-year continuous complete remission (CCR) (P=.031) when
      compared with ITM. CONCLUSION: Intensification with repeated i.v. MTX in the
      setting of low-dose LCV rescue was associated with a higher risk for acute NT and
      LE, especially in patients who received concomitant TIT. The long-term
      consequences for affected patients remain unknown.

PMID- 9586874
TI  - What you don't know can hurt you: adverse psychologic effects in members of BRCA1
      linked and BRCA2-linked families who decline genetic testing.
AB  - PURPOSE: To identify members of hereditary breast and ovarian cancer families who
      are at risk for adverse psychologic effects of genetic testing. PATIENTS AND
      METHODS: A prospective cohort study with baseline (preeducation) assessments of
      predictor variables (ie, sociodemographic factors, cancer history, and cancer
      related stress symptoms) was performed. The primary outcome variable (presence of
      depressive symptoms) was assessed at baseline and at 1- and 6-month follow-up
      evaluations. Participants were 327 adult male and female members of BRCA1- and
      BRCA2-linked hereditary breast and ovarian cancer families, who were identified
      as carriers, noncarriers, or decliners of genetic testing. RESULTS: The presence
      of cancer-related stress symptoms at baseline was strongly predictive of the
      onset of depressive symptoms in family members who were invited but declined
      testing. Among persons who reported high baseline levels of stress, depression
      rates in decliners increased from 26% at baseline to 47% at 1-month follow-up;
      depression rates in noncarriers decreased and in carriers showed no change (odds
      ratio [OR] for decliners v noncarriers=8.0; 95% confidence interval [CI], 1.9 to
      33.5; P=.0004). These significant differences in depression rates were still
      evident at the 6-month follow-up evaluation (P=.04). CONCLUSION: In BRCA1/2
      linked families, persons with high levels of cancer-related stress who decline
      genetic testing may be at risk for depression. These family members may benefit
      from education and counseling, even if they ultimately elect not to be tested,
      and should be monitored for potential adverse effects.

PMID- 9586878
TI  - Tumor clearance of technetium 99m-sestamibi as a predictor of response to
      neoadjuvant chemotherapy for locally advanced breast cancer.
AB  - PURPOSE: Since we have previously shown that the efflux rate of technetium 99m
      (99mTc) sestamibi, a transport substrate of P-glycoprotein (Pgp), is directly
      correlated with Pgp levels in untreated breast carcinoma, we tested whether tumor
      clearance of 9mTc-sestamibi may be predictive of therapeutic response to
      neoadjuvant chemotherapy in patients with locally advanced breast cancer.
      PATIENTS AND METHODS: Thirty-nine patients with stage III disease, median tumor
      diameter 5.8 cm (range, 3 to 10) were enrolled onto this prospective clinical
      trial and underwent 99mTc-sestamibi scan before neoadjuvant chemotherapy.
      Patients were injected intravenously (i.v.) with 740 MBq of 99mTc-sestamibi; a 15
      minute dynamic study was performed, and static planar images were obtained at
      0.5, 1, 2, and 4 hours. The time to half clearance of 99mTc-sestamibi was
      calculated in each patient from decay corrected time-activity curves using a
      monoexponential fitting. Patients were treated with epirubicin 150 mg/m2 i.v.
      every 2 weeks for three courses and then underwent surgery within 3 weeks from
      the completion of chemotherapy. Residual tumor was assessed by pathologic
      examination of mastectomy specimens. RESULTS: Seventeen of 39 patients showed a
      rapid tumor clearance of 9mTc-sestamibi (time to half clearance [t1/2] < or = 204
      minutes) and 15 of these 17 (88%) showed a highly cellular macroscopic residual
      tumor at histology that indicated lack of tumor response to neoadjuvant
      chemotherapy. In contrast, only eight of 22 (36%) with prolonged retention of
      99mTc-sestamibi (t1/2 > 204 minutes) showed residual macroscopic tumor at
      histology (Fisher's exact test, P < .01). CONCLUSION: A rapid tumor clearance of
      99mTc-sestamibi may predict lack of tumor response to neoadjuvant chemotherapy
      with drugs affected by the multidrug-resistant phenotype in patients with locally
      advanced breast carcinoma.

PMID- 9586885
TI  - Cancer in human immunodeficiency virus-infected children: a case series from the
      Children's Cancer Group and the National Cancer Institute.
AB  - PURPOSE: To describe the spectrum of malignancies in human immunodeficiency virus
      (HIV)-infected children and the clinical outcome of patients with these tumors.
      METHODS: We retrospectively surveyed the Children's Cancer Group (CCG) and the
      National Cancer Institute (NCI) for cases of cancer that occurred between July
      1982 and February 1997 in children who were HIV seropositive before or at the
      time of cancer diagnosis. We used Kaplan-Meier survivorship curves, hazard
      function estimates, and Cox proportional hazards models to evaluate survival.
      RESULTS: Sixty-four children (39 boys, 25 girls) with 65 tumors were reported.
      Thirty-seven children (58%) acquired HIV infection vertically (median age at
      cancer diagnosis, 4.3 years); 22 children (34%) acquired HIV through transfusion
      of blood or blood products (median age at cancer diagnosis, 13.4 years). Forty
      two children (65%) had non-Hodgkin's lymphoma (NHL). Eleven children (17%) had
      leiomyosarcomas (or leiomyomas), which are otherwise exceptionally rare in
      children. Other malignancies included acute leukemia (five children), Kaposi's
      sarcoma (KS; three children), Hodgkin's disease (two children), vaginal carcinoma
      in situ (one child), and tracheal neuroendocrine carcinoma (one child). Median
      survival after NHL diagnosis was 6 months (range, 1 day to 89 months) and after
      leiomyosarcoma was 12 months (range, 10 days to 19 months). The average monthly
      death rate after NHL diagnosis was 12% in the first 6 months, which decreased to
      about 2% thereafter. In contrast, the monthly death rate after leiomyosarcoma
      diagnosis increased from 5% in the first 6 months to about 20% thereafter.
      CONCLUSION: After NHL, leiomyosarcoma is the second leading cancer in children
      with HIV infection. Both cancers have high mortality rates; improved outcome for
      NHL, in particular, may depend on earlier diagnosis and therapy.

PMID- 9586886
TI  - Prospective randomized trial of two dose levels of interferon alfa with
      zidovudine for the treatment of Kaposi's sarcoma associated with human
      immunodeficiency virus infection: a Canadian HIV Clinical Trials Network study.
AB  - PURPOSE: Interferon alfa alone has shown antitumor activity against Kaposi's
      sarcoma (KS), and phase I and II clinical trials showed that interferon and
      zidovudine could be administered safely to patients with human immunodeficiency
      virus (HIV)-associated KS. These observations led to our trial of zidovudine with
      two dose levels of interferon alfa. METHODS: HIV-positive patients with KS were
      eligible if they were older than 18 years of age, had a performance status of 0
      to 2, and were free of active infection. All patients received zidovudine 500 mg
      daily and were randomized to receive-interferon alfa 1 million U or 8 million U
      subcutaneously daily. RESULTS: The 108 eligible and assessable patients were well
      balanced for known prognostic factors. Response was reported in 31% of high-dose
      therapy and 8% of low-dose therapy patients (P=.011). Response at both dose
      levels was higher for patients with CD4 counts greater than 150 x 10(9)/L. The
      median time to progression was longer for patients in the 8-million U arm (18 v
      13 weeks; P=.002). Both hematologic and nonhematologic toxicities were higher in
      the high-dose arm; 50 of 54 patients who received 8 million U required dose
      alterations in the first 4 months compared with only 19 of 53 patients who
      received 1 million U (P=.0002). No significant differences were reported with
      respect to improvement in CD4 count, elimination of p24 antigen, or development
      of opportunistic infections. CONCLUSION: Zidovudine and moderate-dose-interferon
      alfa may be combined safely for the treatment of HIV-associated KS, and both
      response to treatment and toxicity are dose related.

PMID- 9586890
TI  - Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography
      in staging of regional lymph nodes in patients with cutaneous malignant melanoma.
AB  - PURPOSE: To assess prospectively the accuracy of 2-[l8F]-2-deoxy-D-glucose
      positron emission tomography (FDG-PET) for predicting regional node involvement
      in cutaneous malignant melanoma (CMM). PATIENTS AND METHODS: Twenty-three
      patients with CMM (primary lesions > 1.5 mm thick) scheduled for lymph node
      dissection (LND) were preoperatively studied with FDG-PET. Thirteen patients
      underwent therapeutic LND of 14 node basins, while nine patients had elective LND
      of 10 node basins. Medical problems precluded surgery in one patient. Two
      observers unaware of the clinical node status-apart from whether a recent
      surgical scar was present-read attenuation-corrected reconstructed transverse
      images acquired between 50 and 60 minutes after injection. Intensity of FDG
      uptake was scored as 0 to 3 + on a semiquantitative four-point scale: 0, no
      uptake; 1 +, faint; 2 +, moderate; and 3 +, intense uptake. A node group was
      considered positive on FDG-PET if it contained at least one focus of FDG uptake
      of > or = 2+ intensity. Histopathologic examination of the 24 dissected node
      groups served as a reference. RESULTS: Considering regional node basins, PET
      imaging demonstrated 11 true-positive (TP), 10 true-negative (TN), two false
      negative (FN), and one false-positive (FP) result, for an overall accuracy of
      88%. Histopathologic from one FN case showed seven malignant cells in a marginal
      node sinus. The FP was due to reactive changes postbiopsy. In one patient,
      clinically involved lymph nodes were correctly categorized TN by PET. At least
      four additional 2 + foci seen outside the dissected regions on PET may represent
      metastases and are being monitored. CONCLUSION: FDG-PET accurately predicted
      regional node status in 88% of CMM cases. The failure to detect micrometastatic
      disease may be due to the limitations of the imaging equipment and technique used
      here.

PMID- 9586889
TI  - Polymerase chain reaction detection of melanoma cells in the circulation:
      relation to clinical stage, surgical treatment, and recurrence from melanoma.
AB  - PURPOSE: The detection of melanoma cells in the circulation by polymerase chain
      reaction (PCR) assays has been shown by several investigators to correlate with
      the stage of the disease and possibly with prognosis. PATIENTS AND METHODS: We
      performed prospective studies on 276 patients with primary melanoma and regional
      lymph node (LN) metastases to assess the predictive value of PCR detection of
      tyrosinase and melanoma antigen recognized by T cells-1 (MART-1) in the blood for
      recurrence of melanoma. RESULTS: PCR tests for gp 100, Muc-18, and p97 reacted
      with RNA in blood from healthy subjects and were considered unsuitable for
      patient monitoring. The tests were most frequently positive in the first 3 months
      after surgery. There were 47 recurrences in 123 patients who had been followed up
      for 18 months. Assays within 3 months of surgery predicted recurrence from
      melanoma in 66% of the latter (tests for tyrosinase alone detected 51% and MART-1
      alone 21% of the patients). Hence, 34% of recurrences were not predicted by tests
      in the early postoperative period. This did not appear to be because of marker
      negative melanoma because summation of tests over the first year identified 89%
      of those with recurrent disease. CONCLUSION: Positive tests were recorded in 35%
      of patients who remained disease free, but it is too early to assess whether
      these represent false-positive results. The false-negative results raise the
      question of whether the assays will provide a reliable basis for selection of
      patients for adjuvant therapy.

PMID- 9586887
TI  - Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus
      dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and
      tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative
      Oncology Group study.
AB  - PURPOSE: To investigate the response rate, time to treatment failure (TTF),
      overall survival, and toxicity in patients with metastatic melanoma treated with
      dacarbazine alone, dacarbazine plus interferon (IFN), dacarbazine plus tamoxifen
      (TMX), or dacarbazine plus IFN plus TMX. MATERIALS AND METHODS: Two hundred
      seventy-one patients (258 were eligible) were randomized in a 2 x 2 factorial
      design to receive one of the above treatments. The trial was designed to detect a
      50% improvement in survival with 83% power. RESULTS: Nine complete (CRs) and 18
      partial responses (PRs) were observed in the patients who received treatments
      that contained IFN compared with four CRs and 18 PRs in the patients who received
      treatments that did not contain IFN. Five CRs and 20 PRs occurred in patients
      treated with TMX compared with eight CRs and 16 PRs in those treated without TMX.
      Response differences were nonsignificant. The overall median TTF was 2.6 months,
      and the overall median survival was 8.9 months. There was no significant
      difference in TTF or survival among any of the different treatments. Poor
      performance status (PS), hepatic metastases, and weight loss were significant
      adverse prognostic factors. Twenty-three patients had a TTF greater than 20
      months, and these durable responses were evenly distributed among the treatment
      arms. Significantly more severe and life-threatening toxic events occurred with
      treatments that contained IFN. CONCLUSION: Neither IFN, TMX, nor the combination
      significantly improved the response rate, TTF, or survival when added to
      dacarbazine, but IFN significantly increased toxicity.

PMID- 9586892
TI  - Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year
      outcome of a multicenter randomized trial.
AB  - PURPOSE: As previously shown, antibody treatment increased survival of patients
      with resected colorectal cancer of stage Dukes' C. Since the 5-year analysis was
      criticized because of the wide range (2.7 to 7.5 years) of follow-up time, we
      performed a 7-year analysis with only four of 189 patients monitored for less
      than 5 years. PATIENTS AND METHODS: A total of 189 patients with resected Dukes'
      C colorectal cancer were randomly allocated to infusions of a total of 900 mg 17
      1A antibody, 500 mg postoperatively followed by 4 monthly doses of 100 mg (n=99),
      or to observation only (n=90). Primary end points were overall survival and
      disease-free interval. Patients were stratified by a dynamic randomization
      according to center, sex, location of tumor, number of affected lymph nodes, and
      preoperative carcinoembryonic antigen concentration. RESULTS: Randomization
      produced balanced distribution of risk factors. After 7 years of follow-up
      evaluation, treatment had reduced overall mortality by 32% (Cox's proportional
      hazard, P < .01; log-rank, P=.01) and decreased the recurrence rate by 23% (Cox's
      proportional hazard, P < .04; log-rank, P=.07). The intention-to-treat analysis
      gave a significant effect for overall survival (Cox's proportional hazard, P <
      .01; log-rank, P=.02) and disease-free survival (Cox's proportional hazard,
      P=.02; log-rank, P=.11 ). While distant metastases were significantly reduced
      (Cox's proportional hazard, P=.004; log-rank, P=.004), local relapses were not
      (Cox's proportional hazard, P=.65; log-rank, P=.52). This differential effect of
      17-1A antibody on disseminated isolated tumor cells versus occult local
      satellites may explain the increased significance seen in the overall survival.
      CONCLUSION: The now-matured study shows that 17-1A antibody administered after
      surgery prevents the development of distant metastasis in approximately one third
      of patients. The therapeutic effect is maintained after 7 years of follow-up
      evaluation.

PMID- 9586891
TI  - Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer
      with technetium 99m-labeled totally human monoclonal antibody 88BV59: results of
      pivotal, phase III multicenter studies.
AB  - PURPOSE: To assess the performance and potential clinical impact of a totally
      human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in
      202 assessable presurgical patients with recurrent, metastatic, or occult
      colorectal cancer. METHODS: 88BV59, labeled with technetium Tc 99m (99mTc)
      (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission
      tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical
      and pathologic verification of tumor were used as the standard against which the
      performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were
      evaluated. RESULTS: All patients entered onto the recurrent disease study had at
      least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT
      positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with
      17% for CT and the difference was statistically significant (P < .001). The
      diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved
      the accuracy of the identification of resectable and nonresectable disease over
      that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001)
      reduction versus CT in terms of the proportion of patients understaged (27% v
      41%) and overstaged (4% v 26%). In patients with occult disease (increasing
      carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT),
      HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT
      Tc images provided additional clinical data that would have affected patient
      management decisions in 40 of 202 (19.8%) patients. In 365 patients who received
      88BV59, only a single detectable human anti-human antibody (HAHA) response (90
      ng/mL) at 9 weeks postinfusion was observed. CONCLUSION: HumaSPECT-Tc can provide
      important and accurate information about the presence and location of disease in
      patients with a high clinical suspicion of metastatic or recurrent colorectal
      cancer and either positive (known disease) or negative (occult disease) CT scans.

PMID- 9586893
TI  - Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine.
AB  - PURPOSE: To evaluate the toxicology and pharmacology of an orally active
      fluoropyrimidine given as a continuous daily dose divided into two portions for 6
      weeks, and to determine the maximal-tolerated daily dose (MTD) and the suggested
      phase II daily dose. PATIENTS AND METHODS: Solid-tumor patients with a Karnofsky
      performance status greater than 70 who had normal organ function and resolution
      of the effects of prior therapy, and who gave informed written consent, were
      enrolled. Oral capecitabine, as a divided morning and evening dose, was
      administered to cohorts of a minimum of 3 patients starting at 110 mg/m2 and
      escalating by means of a modified Fibonacci scheme to 1,657 mg/m2/d.
      Pharmacologic samples were obtained on days 1 and 15. Toxicity evaluations were
      performed approximately every 3 days for the first 43 days. Antitumor effect was
      evaluated at day 42 of therapy. RESULTS: Thirty-three patients entered the study.
      Few side effects occurred at or below 1,331 mg/m2/d. The MTD was 1,657 mg/m2/d
      with limiting toxicities of palmar-plantar erythrodysesthesia, nausea, vomiting,
      vertigo, abdominal pain, diarrhea, and thrombocytopenia. All toxicities were
      reversible. A mixed response was seen in one breast cancer patient. Pharmacologic
      studies showed rapid and extensive metabolism of the parent drug into cytotoxic
      metabolites with a maximum plasma concentration (Cmax) 1 hour after ingestion.
      Linear increases in the area under the concentration-time curve (AUC) and Cmax
      were seen with linear increases in administered dose. CONCLUSION: The suggested
      phase II dose on a continuous 42-day dosing schedule is 1,331 mg/m2/d. Linear
      pharmacologic parameters of the parent compound and metabolites are demonstrated.

PMID- 9586896
TI  - Multicenter phase II trial of interleukin-2, interferon-alpha, and 13-cis
      retinoic acid in patients with metastatic renal-cell carcinoma.
AB  - PURPOSE: To determine the response rate and toxicity of oral 13-cis-retinoic acid
      (CRA) added to an outpatient regimen of subcutaneous interleukin-2 (IL2) and
      interferon-alpha (IFNA) in previously untreated patients with metastatic renal
      cell carcinoma (RCC). PATIENTS AND METHODS: Eligibility included a performance
      status of 2 or better, no significant end-organ dysfunction, and written informed
      consent. Characteristics of 47 of 48 assessable patients included a median
      performance status of 0, prior nephrectomy in 68% of patients, one metastatic
      site in 30% of patients, and lung-only metastatic disease in 21% of patients.
      Therapy consisted of IL2 11 x 10(6) IU 4 days per week for 4 weeks, IFNA 9 x
      10(6) IU 2 days per week for 4 weeks, and CRA 1 mg/kg daily on a 6-week cycle.
      RESULTS: Eight of 47 patients (17%) responded (one complete response, seven
      partial responses). Three partial responders were rendered disease free by
      subsequent surgical resection. Four additional patients experienced a minor
      response in lung or soft tissue metastases. The median duration of response,
      which included minor responses, was 42 weeks, and median survival was 74 weeks
      (17 months). Grades 3 or greater toxicities during the first cycle included flu
      like symptoms (21% of patients), fatigue (6% of patients), and nausea and
      vomiting (15% of patients). Significant cumulative toxicities were hyperlipidemia
      (four of 18 patients), and cardiomyopathy (one of 18 patients). There was one
      therapy-related death. CONCLUSION: Outpatient CRA plus IL2 and IFNA is feasible
      and modestly effective in metastatic RCC. The prolonged median survival is
      encouraging, but randomized trials are required to show that the combination
      represents an improvement over single-agent immunotherapy.

PMID- 9586894
TI  - O6-benzylguanine in humans: metabolic, pharmacokinetic, and pharmacodynamic
      findings.
AB  - PURPOSE: O6-Benzylguanine is a potent inactivator of the DNA-repair protein, O6
      alkylguanine-DNA alkyl-transferase (AGT), that enhances sensitivity to
      nitrosoureas in tumor-cell lines and tumor-bearing animals. The objective of this
      study was to determine the pharmacokinetics and metabolic fate of O6
      Benzylguanine in humans and its effect on AGT activity in peripheral-blood
      mononuclear cells (PBMCs). PATIENTS AND METHODS: Twenty-five cancer patients were
      treated with O6-Benzylguanine at a dose level of 10, 20, 40, and 80 mg/m2
      intravenously (IV) over 1 hour. Plasma and urine samples were collected and
      analyzed for O6-Benzylguanine and O6-Benzyl-8-oxoguanine concentrations. AGT
      activity in PBMCs was determined up to 2 weeks postinfusion. RESULTS: There was
      no toxicity attributable to O6-Benzylguanine alone at all doses tested. O6
      Benzylguanine rapidly disappeared from plasma and was converted to a major
      metabolite, O6-Benzyl-8-oxoguanine. The half-life of O6-Benzyl-8-oxoguanine
      increased with dose from 2.8 to 9.2 hours at doses of 10 and 80 mg/m2,
      respectively. The maximum concentration Cmax and area under the concentration
      time curve (AUC) for O6-Benzyl-8-oxoguanine were, respectively, 2.2- and 12- to
      29-fold greater than those of O6-Benzylguanine. At all doses, depletion of AGT
      activity was observed in lymphocytes with a return to baseline by 1 week
      posttreatment. CONCLUSION: This study demonstrates that administration of O6
      Benzylguanine to humans results in a rapid conversion to O6-Benzyl-8-oxoguanine,
      which follows nonlinear kinetics. Both compounds contribute to an effective
      depletion of AGT activity in lymphocytes; however, prolonged depletion of AGT
      activity is likely due primarily to the effect of O6-Benzyl-8-oxoguanine.

PMID- 9586895
TI  - Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic
      dysfunction: Cancer and Leukemia Group B 9264.
AB  - PURPOSE: To characterize the maximum-tolerated dose, dose-limiting toxicities
      (DLTs), and pharmacokinetics of paclitaxel in patients with abnormal liver
      function. PATIENTS AND METHODS: Adults with tumors appropriate for paclitaxel
      therapy who had abnormal liver function tests were eligible. Patients were
      assigned to one of three treatment cohorts: I, AST level twofold normal and
      bilirubin level less than 1.5 mg/dL; II, bilirubin level 1.6 to 3.0 mg/dL; and
      III, bilirubin level greater than 3.0 mg/dL. Doses were explored in at least
      three patients within each cohort. Although designed to assess a 24-hour infusion
      schedule, the trial was extended to also assess a 3-hour regimen.
      Pharmacokinetics were to be studied in all patients. RESULTS: Eighty-one patients
      were assessable for toxicity. Patients with bilirubin levels greater than 1.5
      mg/dL had substantial toxicity at all doses explored, whereas the toxicity for
      patients with elevated AST levels occurred at doses that ranged from 50 to 175
      mg/m2 administered over 24 hours. In most patients, the DLT was myelosuppression.
      The pharmacokinetic data were insufficient to adequately evaluate the
      relationship between pharmacokinetics and toxicity in patients who received 24
      hour infusions but provided evidence of a longer exposure to paclitaxel than
      anticipated for the doses used in this study in the 3-hour infusion group.
      CONCLUSION: If paclitaxel is used for patients with elevated levels of AST or
      bilirubin, dose reductions are necessary, and an increase in toxicity can be
      anticipated. The increased myelosuppression observed is at least partially
      because of altered paclitaxel pharmacokinetics in such patients.

PMID- 9586897
TI  - Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with
      advanced carcinoma of the esophagus.
AB  - PURPOSE: We have previously identified paclitaxel as an active single agent in
      the treatment of esophageal cancer. We performed a phase II trial of paclitaxel
      in combination with cisplatin and fluorouracil (5-FU), conventionally used
      chemotherapy for esophageal cancer. The antitumor response, toxicity, and
      survival of patients treated with the three-drug regimen were evaluated. PATIENTS
      AND METHODS: Sixty-one patients with advanced, surgically unresectable, or
      metastatic squamous cell or adenocarcinoma of the esophagus were treated. No
      prior chemotherapy was allowed. Thirty patients had adenocarcinoma and 31
      patients had squamous cell carcinoma. The majority (47 patients; 77%) had
      metastatic disease and 14 patients (23%) had an unresectable primary or locally
      recurrent tumor. Patients received paclitaxel 175 mg/m2 by 3-hour infusion day 1;
      cisplatin 20 mg/m2 daily days 1 through 5, and 5-FU by continuous infusion at a
      dose of 1,000 mg/m2 daily days 1 through 5. Because of toxicity observed in the
      first 10 patients treated, the starting dose of 5-FU was subsequently reduced to
      750 mg/m2 daily in the remaining patients. A planned attenuation of cisplatin to
      15 mg/m2 daily was made after the first three cycles. Granulocyte colony
      stimulating factor (G-CSF) was not routinely administered unless the patient had
      an episode of febrile neutropenia or prolonged grade 4 neutropenia. Treatment was
      recycled every 28 days. RESULTS: Sixty-one patients completed a median of five
      cycles, and 60 patients were assessable for response. Major responses were seen
      in 29 patients (48%; 95% confidence intervals, 35 to 61), which included seven
      complete responses (12%). Comparable response rates were seen for patients with
      adenocarcinoma (46%) and those with squamous carcinoma (50%), and for patients
      with metastatic disease (22 of 46 patients; 48%) and those with locally advanced
      disease (seven of 14 patients; 50%). A significantly higher complete response
      rate was observed in patients with squamous carcinoma (20%) compared with those
      with adenocarcinoma (3%; chi2 P=.04). The median duration of response was 5.7
      months (range, 1 to 18.6 months). Median survival was 10.8 months (range, 1.5 to
      25 months). Toxicity was severe but manageable with dose attenuation, and
      included 18% of patients with grade 3 neurologic toxicity. Twenty-eight patients
      (46%) required a dose attenuation for toxicity, and 42 of 275 treatment cycles
      (15%) required a dose attenuation. Twenty-nine patients (48%) required
      hospitalization for toxicity, which included 11 patients for neutropenic fever
      (18%). There were no treatment-related deaths. CONCLUSION: The combination of
      paclitaxel, cisplatin, and 5-FU has substantial antitumor activity in metastatic
      esophageal carcinoma, with a remarkable complete response rate noted in patients
      with squamous carcinoma. Paclitaxel is an important new agent in the treatment of
      esophageal carcinoma, and further evaluation of this agent in combination
      chemotherapy is warranted. Given the toxicity associated with the current
      regimen, the optimal dose and schedule of paclitaxel in combination chemotherapy
      remain to be established.

PMID- 9586898
TI  - Change in serum prostate-specific antigen as a marker of response to cytotoxic
      therapy for hormone-refractory prostate cancer.
AB  - PURPOSE: Prostate-specific antigen (PSA) has been used as a marker of advanced
      prostate cancer but remains controversial. To evaluate PSA as a predictor of
      survival, we analyzed data from sequential phase II trials of estramustine and
      etoposide. METHODS: A landmark analysis that used data from 62 men with PSA
      levels at baseline and 8 weeks was conducted. The best PSA measure (of six
      evaluated) was incorporated into a multiple regression model with performance
      status (PS); relative change in PSA level; and pretreatment PSA, alkaline
      phosphatase, and hemoglobin values. RESULTS: A decrease in PSA of 50% or greater
      at 8 weeks was associated with a significantly increased survival (P=.0005, two
      sided log-rank test). Median survival from the landmark was 91 weeks in patients
      with a 50% or greater decrease at 8 weeks versus 38 weeks in those without this
      decrease. Modeling showed that PS, pretreatment hemoglobin level, and relative
      change in PSA level were significant prognostic factors, with a significant
      interaction between PS and pretreatment hemoglobin level. In the final model, a
      relative change in PSA level at 8 weeks of less than 50% had an adjusted relative
      risk of 2.20 (95% confidence interval, 1.21 to 4.00). A decrease in PSA level of
      50% or greater at any time during therapy was associated with a response in
      measurable disease (P=.0369, two-sided Fisher's exact test). CONCLUSION: The PSA
      value after 8 weeks of this cytotoxic regimen does predict survival. A decrease
      in PSA level is associated with both survival and response in soft tissue lesions
      and should be incorporated into the response criteria and reporting of trials of
      cytotoxic agents in prostate cancer.

PMID- 9586888
TI  - Development of a biochemotherapy regimen with concurrent administration of
      cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for
      patients with metastatic melanoma.
AB  - PURPOSE: To evaluate the antitumor activity and toxicity of concurrent
      biochemotherapy that uses cisplatin, vinblastine, and docarbazine (DTIC) (CVD) in
      combination with interferon alfa-2a (IFN-alpha) and interleukin-2 (IL-2) in
      patients with metastatic melanoma. PATIENTS AND METHODS: Between October 1992 and
      October 1993, 53 patients with a documented diagnosis of metastatic melanoma with
      measurable lesions and an Eastern Oncology Cooperative Group (ECOG) performance
      status of 2 or less were enrolled onto this study. Patients were required to have
      no clinically significant cardiac dysfunction and to be free from symptomatic
      brain metastases. The treatment consisted of cisplatin 20 mg/m2 daily for 4 days;
      vinblastine 1.6 mg/m2 daily for 4 days; and DTIC 800 mg/m2 intravenously (i.v.)
      day 1 with IL-2 9 x 10(6) IU/m2 i.v. by continuous infusion daily for 4 days and
      IFN-alpha 5 x 10(6) U/m2 subcutaneously daily for 5 days, repeated at 21-day
      intervals. Response was assessed after two cycles and patients who responded were
      continued on treatment for a total of six cycles. RESULTS: Among 53 assessable
      patients, 11 patients (21%) achieved a complete response (CR) and 23 patients
      (43%) achieved a partial response (PR), for an overall objective response rate of
      64%. The median time to disease progression for all patients was 5 months. The
      median survival of all patients entered onto the trial was 11.8 months. Among the
      11 patients who achieved a CR, five patients (9%) have remained in continuous CR
      for 50+ to 61+ months. The toxicity of biochemotherapy consisted of severe
      myelosuppression, significant nausea and vomiting, and moderately severe
      hypotension that required inpatient hospital care for each 5-day cycle of
      treatment. There were no treatment-related deaths. CONCLUSION: Concurrent
      biochemotherapy for patients with advanced melanoma is capable of producing high
      CR and overall response rates and resulted in durable complete remissions in a
      small fraction of patients. Toxicity, although severe, was manageable in a
      routine inpatient hospital environment.

PMID- 9586900
TI  - Ninety-six-hour infusional paclitaxel as salvage therapy of ovarian cancer
      patients previously failing treatment with 3-hour or 24-hour paclitaxel infusion
      regimens.
AB  - PURPOSE: To test the hypothesis that prolonged infusion of paclitaxel (96 hours)
      might overcome resistance to shorter infusion schedules (3 or 24 hours) in
      ovarian cancer. PATIENTS AND METHODS: A total of 30 patients with advanced
      ovarian cancer (24 patients), primary carcinoma of the peritoneum (four
      patients), or fallopian tube cancer (two patients) who previously had received
      paclitaxel administered on either a 3-hour or 24-hour schedule were treated with
      the agent delivered as a 96-hour infusion (30 to 35 mg/m2/d x 4 days) on an every
      3-week program. RESULTS: Although the regimen generally was well tolerated, no
      objective responses were observed. CONCLUSION: In patients with ovarian cancer
      who have shown resistance to shorter paclitaxel infusion schedules, ninety-six
      hour infusional paclitaxel is an inactive treatment strategy. This makes it less
      likely that protracted infusion of paclitaxel will improve outcome when used as
      part of primary therapy of ovarian cancer. An ongoing randomized study will
      answer that question.

PMID- 9586899
TI  - Phase II trial of paclitaxel and carboplatin in the treatment of advanced
      urothelial carcinoma.
AB  - PURPOSE: Both paclitaxel and carboplatin have single-agent activity against
      carcinoma of the urothelium. We evaluated the combination of paclitaxel and
      carboplatin in the treatment of advanced cancers of the urothelium. PATIENTS AND
      METHODS: Patients with cancers of the urothelium who had no prior chemotherapy
      (prior adjuvant chemotherapy > 6 months allowed) were eligible for treatment.
      Eligibility requirements were performance status of 2 or less, creatinine level
      less than 2.0 mg/dL, granulocyte count (AGC) 1,500/microL or greater, platelet
      count 100,000/microL or greater, and total bilirubin level less than 1.5 mg/dL.
      Paclitaxel 200 mg/m2 followed by carboplatin (area under the curve [AUC] 5,
      Calvert formula) were administered every 21 days. Patients were evaluated for
      toxicity weekly and assessed for response every 6 weeks. RESULTS: Thirty-six
      patients were entered onto the study and 35 patients were assessable for
      response. A total of 184 cycles were administered (median, six cycles per
      patient). Nine patients required one dose reduction, and seven patients required
      two dose reductions for a nadir AGC less than 500/microL, with only one episode
      of febrile neutropenia and sepsis. Myalgias and arthralgias of grades 1 to 2
      occurred in 16 patients and usually lasted 2 to 3 days after treatment. There
      were no treatment delays because of toxicity. There were 18 responses; seven
      complete responses (CRs) and 11 partial responses (PRs) (response rate 51.5%; 95%
      confidence interval, 35 to 68). Median response durations for CR and PR were 6
      and 4 months, respectively. Overall median survival was 9.5 months. CONCLUSION:
      The combination of paclitaxel and carboplatin is an active and well-tolerated
      regimen for the treatment of advanced urothelial carcinoma. Because of the modest
      toxicity of this combination, paclitaxel and carboplatin should be considered for
      addition to other agents with activity in urothelial carcinomas.

PMID- 9586902
TI  - Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer.
AB  - PURPOSE: The clinical impact of endogenous cytokines supplied with deterministic
      properties in the generation of either T helper (Th)1 -type or Th2-type immune
      response was investigated in patients with ovarian cancer. Whereas interleukin
      (IL)- 12 initiates the differentiation of naive Th0 cells toward Th1 phenotype,
      IL-4 and IL-10 mediate the development of Th2-type immunity. PATIENTS AND
      METHODS: Cytokines were determined before treatment by means of enzyme-linked
      immunosorbent assay (ELISA) in ascites fluid and serum of 76 patients with
      ovarian cancer. Cytokine levels were compared with each other and with standard
      clinicopathologic parameters. A stepwise logistic regression was calculated to
      rule out interdependence in the associations of the various variables. Survival
      analyses were performed with the Kaplan-Meier method and differences in survival
      were examined according to Mantel and Breslow. Cox proportional hazards analysis
      was used to identify independent prognostic factors. RESULTS: Whereas IL-10 and
      IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in only
      43% of the specimens. With the exception of neopterin, macrophage colony
      stimulating factor (M-CSF), and IL-4, determined cytokine levels were
      significantly elevated in ascites fluid compared with serum (P < .01). In
      univariate analyses, high ascitic-fluid concentrations of either neopterin, tumor
      necrosis factor-alpha (TNF-alpha), or IL-12 were associated with poor disease
      free (P < .005) and overall (P < .01) survival. Multivariate Cox regression
      analysis showed ascitic-fluid IL-12 levels to be the only immunologic variable
      that retained independent prognostic significance (P < .03 for disease-free and P
      < .01 for overall survival), together with residual disease, Federation
      Internationale de Gynecologie et d'Obstetrique (FIGO)-stage, and patient age.
      CONCLUSION: In ovarian cancer, high ascitic-fluid IL-12 levels, which may
      indicate a local Th1-generated immune response, are associated with disease
      progression.

PMID- 9586904
TI  - Chemotherapy for cervical carcinoma: factors determining response and
      implications for clinical trial design.
AB  - PURPOSE: To identify characteristics that predict response to chemotherapy in
      patients with advanced or recurrent squamous cell carcinoma of the cervix.
      PATIENTS AND METHODS: Between January 1986 and May 1996, 190 chemotherapy-naive
      patients with advanced or recurrent squamous cell carcinoma of the cervix not
      amenable to curative radiation therapy or surgery were treated on 14 different
      chemotherapy protocols at M.D. Anderson Cancer Center. Patient's charts were
      retrospectively reviewed for patient demographics, tumor and treatment
      characteristics, and patterns of response and survival. RESULTS: Of 190 patients,
      22 had advanced or persistent disease and 168 had recurrent disease. Patients
      were treated with platinum-based (n=95) and non-platinum-based (n=95) regimens.
      The overall response rate was 20.0% (4.2% complete response; 15.8% partial
      response), with a median response duration of 4.8 months. Race, socioeconomic
      class, tumor stage and grade, mode of primary treatment, time from primary
      diagnosis to disease recurrence, initial performance status, and use of platinum
      based therapy were not significant predictors of response. Age at time of
      chemotherapy (P=.001) and site of recurrence (P=.044) were significant
      determinants by multivariate analysis. Patients who were older were more likely
      to respond to therapy, and the response rate for patients in whom disease
      recurred outside the irradiated field was 25.2%, compared with a 5.3% response
      rate for patients with recurrent disease limited to a previously irradiated
      field. CONCLUSION: The site of disease recurrence and patient age should be taken
      into account when designing chemotherapy trials and also when considering
      chemotherapy in the patient with recurrent cervix cancer.

PMID- 9586903
TI  - Combination of consecutive low-dose cisplatin with bleomycin, vincristine, and
      mitomycin for recurrent cervical carcinoma.
AB  - PURPOSE: To evaluate the efficacy and toxicity of combination chemotherapy with
      bleomycin, vincristine, mitomycin, and consecutive low-dose (CLD) administration
      of cisplatin (CLD-BOMP) for patients with recurrent cervical carcinoma. PATIENTS
      AND METHODS: Ninety patients with recurrent cervical carcinoma and no prior
      chemotherapy were enrolled onto this study. The median age was 56 years. Eighty
      seven of the 90 patients had received prior radiotherapy. The CLD-BOMP regimen
      was bleomycin 5 mg infused continuously days 1 through 7; vincristine 0.7 mg/m2
      bolus day 7; mitomycin 7 mg/m2 bolus day 7; and cisplatin 10 mg/m2 infused over 4
      hours days 1 through 7. The treatment was repeated at 3-week intervals. RESULTS:
      All 90 patients were assessable for response, toxicity, and survival. After a
      median of four cycles (range, two to 10 cycles), we observed objective responses
      in 68 patients (76%), with 25 (28%) complete responses (CRs) and 43 (48%) partial
      responses (PRs; 95% confidence interval (CI), 66 to 85; 18 to 38; 37 to 59,
      respectively). Median survival for all 90 patients was 24.3 months (range, 2.3 to
      100 months). The median survival for patients who achieved CR, PR, no change
      (NC), and progressive disease (PD) were not reached (NR), 23.6, 8.2, and 6.4
      months, respectively. The median progression-free survival for patients who
      achieved CR and PR were NR and 12.3 months, respectively. There was no
      significant nausea or vomiting, nephrotoxicity, or pulmonary toxicity, which was
      attributable to the CLD-cisplatin and the adequate dosing schedule of bleomycin.
      The reduced toxicities allowed this regimen to be administered at the projected
      dose-intensities. CONCLUSION: The CLD-BOMP regimen has significant antitumor
      activity with markedly reduced toxicity.

PMID- 9586901
TI  - Phase II study of "dose-dense" high-dose chemotherapy treatment with peripheral
      blood progenitor-cell support as primary treatment for patients with advanced
      ovarian cancer.
AB  - PURPOSE: We performed a pilot phase II study to evaluate the potential for
      delivery of rapidly sequenced high-dose chemotherapy treatments rescued with
      autologous peripheral-blood progenitor cells (PBP) in patients with previously
      untreated, advanced ovarian cancer. PATIENTS AND METHODS: A single cycle of
      mobilization was used, primed with cyclophosphamide (CPA)/paclitaxel (Txl) and
      filgrastim (granulocyte colony-stimulating factor [G-CSF]), followed by three
      cycles of high-dose carboplatin (CBDCA)/Txl and one cycle of high-dose melphalan
      (MEL), each rescued by PBP. We then analyzed the outcome for a total of 56
      consecutive patients treated with high-dose chemotherapy as part of this program.
      RESULTS: In the phase II pilot, 21 patients were enrolled. There were no
      treatment-related deaths through 98 high-dose treatments, although 34 treatments
      were complicated by hospitalization, primarily for neutropenic fever. Seventy-six
      percent of patients experienced grade 3 to 4 gastrointestinal toxicity and 62%
      experienced grade 2 to 3 neuropathy. Five of 15 (33%) patients who underwent
      second-look surgery attained a pathologic complete response. In the overall
      analysis, 56 patients were reviewed. Forty-four patients were assessable for
      response by second-look surgery or clinical progression. Fifteen of 44 patients
      achieved a pathologic complete response (34%). The pathologic complete response
      rate in optimal-disease patients was 12 of 22 (55%), while only three of 22 (13%)
      suboptimal stage III and IV patients achieved a pathologic complete response.
      CONCLUSION: The Gynecologic Oncology Group has initiated a pilot phase II trial
      of this approach in patients with optimally debulked stage III ovarian cancer.
      There is no evidence to support the use of this or other aggressive regimens
      outside of a clinical trial.

PMID- 9586907
TI  - Balanced chromosome aberrations in leukemias following chemotherapy with DNA
      topoisomerase II inhibitors.

PMID- 9586905
TI  - Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia.
AB  - PURPOSE: A report of the clinical features, treatment, and outcome of patients
      who developed hemolytic anemia (HA) temporally associated with fludarabine
      (Fludara; Berlex Laboratories, Richmond, CA) therapy for chronic lymphocytic
      leukemia (CLL). PATIENTS AND METHODS: Data on 24 patients who developed HA
      related to fludarabine therapy were collected from the Spontaneous Reporting
      System of the Food and Drug Administration (FDA) and the Walter Reed Army Medical
      Center (Washington, DC). RESULTS: Seventeen (71%) patients developed HA after
      either the first, second, or third cycle of this drug. The longest duration of
      fludarabine therapy before HA occurred was six cycles. The median decline in
      hematocrit from baseline during the hemolytic episode was 14.1 (range, 8.0 to
      28.9) for the 18 patients for whom this information was available. For the 11
      patients for whom transfusion requirements were known, the number of transfusions
      administered ranged between three and 36. Seven (29%) patients died of medical
      complications associated with the HA. Seven of eight patients who were re
      challenged with fludarabine after an episode of HA developed recurrent HA, and
      three of these patients died. CONCLUSION: HA associated with fludarabine therapy
      appears to be uncommon, but it can be severe and fatal, especially if a patient
      is re-treated with this drug after a previous episode of HA. The mechanism of
      this toxicity is unknown, but it may be caused by the release of a suppressed
      auto-antibody to a native red cell antigen.

PMID- 9586906
TI  - Inversion of chromosome 16 and uncommon rearrangements of the CBFB and MYH11
      genes in therapy-related acute myeloid leukemia: rare events related to DNA
      topoisomerase II inhibitors?
AB  - PURPOSE: To evaluate the frequency of inversion of chromosome 16 (inv[16]) and
      the type of rearrangement of the CBFB and MYH11 genes in therapy-related acute
      myeloid leukemia (t-AML) and to evaluate a possible relationship to specific
      types of previous chemotherapy. PATIENTS AND METHODS: Cytogenetic studies were
      performed in 180 consecutive patients with therapy-related myelodysplasia (t-MDS)
      or t-AML in Copenhagen and in 270 consecutive patients in Chicago. Leukemic cells
      were available for studies of the molecular biology in 72 patients, including
      four with inv(16). RESULTS: An inv(16)(p13q22) was observed in only two of 180
      cases of t-MDS and t-AML in Copenhagen and in only four of 270 cases of t-MDS and
      t-AML in Chicago. Four patients with t-AML and inv(16) previously had received
      combination chemotherapy, which included an alkylating agent, and in two a DNA
      topoisomerase II inhibitor was included (mitoxantrone and etoposide). One patient
      had received paclitaxel followed by etoposide and one patient had received
      radiotherapy only. One patient, previously treated with mitoxantrone and
      cyclophosphamide for breast cancer, presented a new and, to our knowledge not
      previously reported, type of fusion transcript, with breakpoint at nt 399 of the
      CBFB gene and at nt 2134 of the MYH11 gene. Two patients previously treated with
      alkylating agents both presented the less common type D transcript, whereas the
      most common A transcript, observed in 80% of acute myeloid leukemia (AML) de novo
      with inv(16), only was observed in the patient treated with paclitaxel and
      etoposide for leiomyosarcoma. Bone marrow or blood cells from 68 patients with t
      MDS and t-AML without an inv(16) all were found to be negative for chimeric
      rearrangement between the CBFB gene and the MYH11 gene. CONCLUSION: The present
      study and a review of the literature shows that inv(16) is an uncommon aberration
      in t-AML and, like balanced translocations to chromosome bands 11q23 and 21q22
      and the t(15;17), often is associated with prior chemotherapy with DNA
      topoisomerase II inhibitors. Breakpoints within the MYH11 gene may vary between t
      AML and AML de novo.

PMID- 9586910
TI  - Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with
      radiation alone.
AB  - PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (MLS)
      has recently been defined as a distinct clinicopathologic entity, often
      associated with Helicobacter pylori infection. Many regard antibiotic therapy as
      the primary treatment of MLS, but in the absence of H pylori infection, or when
      salvage of antibiotic failures is required, gastrectomy and/or chemotherapy have
      frequently been used. This study evaluates the efficacy of low-dose radiotherapy
      alone as an alternative to surgery. PATIENTS AND METHODS: Seventeen patients with
      stage I to II(2) low-grade MLS without evidence of H pylori infection or with
      persistent lymphoma after antibiotic therapy of associated H pylori infection
      were included in this series. Median age was 69 years (range, 39 to 84). Median
      total radiation dose was 30 Gy (range, 28.5 to 43.5 Gy) delivered in 1.5-Gy
      fractions within 4 weeks to the stomach and adjacent lymph nodes. Following
      treatment, all patients underwent endoscopic evaluation and biopsy at a median of
      4 months, at 6-month intervals to 2 years, and annually thereafter. RESULTS: All
      obtained a biopsy-confirmed complete response. At a median follow-up time of 27
      months (range, 11 to 68) from completion of radiotherapy, event-free survival was
      100%. Treatment was well tolerated, with no significant acute side effects. All
      remained asymptomatic at last follow-up. CONCLUSION: These results suggest that
      effective treatment of MLS with low-dose radiation therapy alone is feasible and
      safe, and allows stomach preservation. Longer follow-up evaluation is required to
      determine the long-term efficacy of this treatment approach and its side effects.
      Further studies should clarify the indications for radiotherapy in H pylori
      negative or antibiotic-resistant cases of MLS.

PMID- 9586909
TI  - Emerging role of laparoscopy in the diagnosis of lymphoma.
AB  - PURPOSE: The results of laparoscopic procedures on patients with suspected or
      known lymphoma were analyzed to review the application and define the role of
      laparoscopy in lymphoma. PATIENTS AND METHODS: The hospital records of 94
      patients who underwent 101 procedures between June 1993 and October 1996 were
      reviewed for demographic and clinicopathologic information. RESULTS: The
      procedure was diagnostic in 85 patients, either at primary presentation (48
      patients), possible relapse (21 patients), in the course of treatment (eight
      patients), or of a liver lesion (eight patients). In the remaining 16 patients,
      it was used to stage possible intraabdominal disease. Twenty-seven patients had a
      previous unsuccessful diagnostic procedure. There were no operative deaths and
      eight postoperative complications (8%). The laparoscopy revealed non-Hodgkin's
      lymphoma (NHL) in 48 patients, Hodgkin's disease (HD) in 14 patients, other
      neoplastic conditions in six patients, and benign conditions in 33 patients.
      There was adequate information in all procedures in which lymphoma was diagnosed
      for treatment decisions. There was one false-negative and one nonresult for
      technical reasons. Ten patients commenced chemotherapy before discharge after a
      median delay of 3.5 days. In five of 24 patients (21%) with recurrent or
      persistent lymphoma, the precise diagnosis was significantly different from the
      original one. CONCLUSION: From our experience, laparoscopy can safely provide
      tissue samples of suspected lymphoma for full diagnostic analysis. It should be
      considered when percutaneous biopsy is not technically possible, when chromosomal
      or genetic analysis is needed for treatment decisions, or when the results of
      percutaneous biopsy are inadequate to make therapeutic decisions.

PMID- 9586912
TI  - Clinical outcome in diffuse large B-cell lymphoma is dependent on the
      relationship between different cell-cycle regulator proteins.
AB  - PURPOSE: The goal of this work was to perform a comprehensive exploration of the
      relationship between the clinical outcome of diffuse large B-cell lymphoma
      (DLBCL) and the expression of a panel of tumor suppressor and oncogenic proteins,
      which includes some cell-cycle regulator proteins involved in the p53 pathway.
      PATIENTS AND METHODS: To this end, we collected the clinical data of 141 patients
      with DLBCL and immunohistochemically analyzed diagnostic tumoral tissue from each
      patient for the presence of Ki67 (MIB1, Immuno-tech, Marseille, France), bcl2,
      p53, p21/WAF1, MDM2, and retinoblastoma (Rb) proteins. RESULTS: The results show
      that several proteins are associated with some of the clinical traits analyzed.
      Multivariate analysis showed that an extended overall survival (OS) time was
      associated with low growth fraction, high Rb protein, and low MDM2 expression, as
      well as with known clinical parameters. The probability of inducing a complete
      remission (CR) was only associated with clinical parameters, although univariate
      study showed that a low growth fraction was associated with a higher probability
      of inducing a CR. Univariate study of disease-free survival (DFS) showed that
      tumors with high bcl2 expression and nodal origin have a shorter DFS time,
      although multivariate study only confirmed the adverse effect of bcl2 expression.
      CONCLUSION: Taking all these results into consideration, it seems that although
      the overall outcome for patients with DLBCL is decided by a combination of
      different clinical and biologic variables, the expression of some of these cell
      cycle regulator proteins appears to be specifically associated with the different
      clinical features of tumors.

PMID- 9586916
TI  - Teaching senior oncologists communication skills: results from phase I of a
      comprehensive longitudinal program in the United Kingdom.
AB  - PURPOSE: To determine the communication difficulties experienced by clinicians in
      cancer medicine and to develop, implement, and evaluate communication skills
      training courses. METHODS: One hundred seventy-eight senior clinicians attended 1
      1/2- or 3-day residential courses designed to enhance skills development,
      knowledge acquisition, and personal awareness. Course content included structured
      feedback, video review of interviews, interactive group demonstrations, and
      discussion in groups of four led by trained facilitators. The main outcomes were
      self-rated confidence in key aspects of communication, attitudinal shift toward
      more patient-centered interviewing, perceived changes in personal practice, and
      initiation of teaching programs for junior staff. RESULTS: Less than 35% of the
      participants had received any previous communications training. Time, experience,
      and seniority had not improved skills; before the course, oncologists expressed
      difficulty with 998 different communication issues. Primary problems concerned
      giving complex information, obtaining informed consent, and handling ethnic and
      cultural differences. Confidence ratings for key communication areas were
      significantly improved postcourse (P < .01). Three months postcourse, 95% of the
      physicians reported significant changes in their practice of medicine. Seventy
      five percent had started new teaching initiatives in communication for junior
      clinicians. Clinicians showed positive shifts in attitude toward patients'
      psychosocial needs (P=.0002) and were more patient centered (P=.03). The courses
      were highly rated and 97% would "definitely" recommend them to colleagues.
      CONCLUSION: Oncologists are hampered by inadequate communication skills training
      and will give up time to correct this. Subjective improvements reported
      immediately postcourse were maintained at 3 months. Resources for educational
      initiatives are needed to help both patients and their physicians.

PMID- 9586915
TI  - Psychologic and neuropsychologic functioning of patients with limited small-cell
      lung cancer treated with chemotherapy and radiation therapy with or without
      warfarin: a study by the Cancer and Leukemia Group B.
AB  - PURPOSE: The current study assessed the psychologic and neuropsychologic
      functioning of patients with small-cell lung cancer who were randomized in a
      large clinical trial to receive intensive doxorubicin, cyclophosphamide,
      etoposide (ACE)/cisplatin, cyclophosphamide, etoposide (PCE) chemotherapy and
      radiation therapy (RT) to the primary tumor and prophylactic whole-brain
      irradiation with (regimen I) or without (regimen II) warfarin. PATIENTS AND
      METHODS: Patients' emotional states and cognitive functioning were assessed using
      the Profile of Mood States (POMS) and Trail Making B Test (Trails B),
      respectively. Two hundred ninety-five patients completed the POMS and Trails B at
      pretreatment, 224 patients after the completion of the ACE course of chemotherapy
      (week 9), and 177 patients after the completion of the PCE chemotherapy and RT
      (week 17). RESULTS: No differences on the POMS or Trails B measures were found
      between the two treatment arms as predicted, given that the only difference
      between the two treatment arms was the presence or absence of warfarin. Analysis
      of the POMS revealed that, overall, mean scores remained stable over the course
      of treatment; however, women showed a trend toward higher mean scores, which
      indicated a higher level of distress, compared with men at the pretreatment
      assessment. Examination of cognitive functioning, measured by the Trails B,
      revealed improved performance from baseline to post-ACE chemotherapy, which is
      consistent with a practice effect, but a significant worsening of Trails B scores
      post-RT compared with the pre-RT assessments, which is consistent with impaired
      cognitive functioning because of treatment (P < .0001). CONCLUSION: Emotional
      state, measured by the POMS, did not differ between the groups or change
      significantly over time in this study of small-cell lung cancer patients treated
      with a combination of chemotherapy and RT plus or minus warfarin. However, the
      pattern of relatively stable POMS scores and poorer Trails B performance post-RT
      suggested that this combination of chemotherapy and RT had a negative impact on
      cognitive functioning.

PMID- 9586908
TI  - Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement
      of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell
      factor.
AB  - PURPOSE: To assess the mobilization potential and safety of recombinant human
      stem-cell factor (SCF) when coadministered with filgrastim to untreated women
      with poor-prognosis breast cancer. PATIENTS AND METHODS: Eligible women had
      breast cancer with 10 or more positive axillary nodes, or estrogen receptor
      negative tumor with 4 positive nodes, or stage III disease. Patients were
      randomized to receive SCF plus filgrastim or filgrastim alone. Filgrastim 12
      microg/kg daily was administered for 6 days by continuous subcutaneous infusion.
      SCF was administered by daily subcutaneous injection at 5, 10, or 15 microg/kg
      concurrent with filgrastim for 7 days, or 10 microg/kg daily starting 3 days
      before filgrastim for a total of 10 days (SCF pretreatment). Apheresis was
      performed on days 5, 6, and 7 of filgrastim administration. Patients then had
      three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2 every 28 days,
      each supported by one third of the apheresis product. RESULTS: Sixty-two women
      were treated. Greater yields occurred in patients who received SCF 10 microg/kg
      daily plus filgastim than those who received filgrastim alone (P=.013 for CD34+
      cells; P=.07 for granulocyte-macrophage colony-forming cells [GM-CFCs]). The
      difference was more marked with SCF-pretreatment than concurrent SCF. Fewer
      aphereses were required to reach the predetermined target of peripheral-blood
      progenitor/stem cells (PBPCs) in women who received SCF. SCF was generally well
      tolerated. Hematologic recovery was rapid after each of the three cycles of
      chemotherapy. There was no difference in recovery between the different treatment
      groups. CONCLUSION: Mobilization of PBPCs by filgrastim is significantly enhanced
      by coadministration of SCF, and commencing SCF before filgrastim can optimize
      this effect. SCF has the potential to reduce the number of aphereses required to
      collect a target number of PBPCs.

PMID- 9586911
TI  - Mantle-cell lymphomas have more widespread disease and a slower response to
      chemotherapy compared with follicle-center lymphomas: results of a prospective
      comparative analysis of the German Low-Grade Lymphoma Study Group.
AB  - PURPOSE: To compare mantle-cell lymphomas (MCLs) and follicle-center lymphomas
      (FCLs) for their features of clinical presentation, response to chemotherapy, and
      prognosis on the basis of a prospective randomized clinical trial. PATIENTS AND
      METHODS: Patients with MCL and FCL who entered onto the prospective randomized
      comparison of cyclophosphamide, vincristine, and prednisone (COP) versus
      prednimustine and mitoxantrone (PmM) followed by a second randomization for
      interferon (IFN) maintenance versus observation only. RESULTS: One hundred sixty
      five of 234 patients had FCL and 45 of 234 patients had MCL. With FCL, both sexes
      were equally affected (men, 47%); patients with MCL were predominantly men (78%;
      P < .0004) and had a higher median age (64 v 53 years; P < .0001). Patients with
      MCL also had more widespread disease, reflected by the proportion of patients
      with two or greater extranodal manifestations (43% v 21%; P < .005) and nine or
      greater involved nodal areas (64% v 45%; nonsignificant [NS]). Response to
      chemotherapy was significantly lower in patients with MCL (complete remission
      [CR] + partial remission [PR], 69% v 88%; P < .05) and occurred at a slower pace.
      Patients with MCL also had a shorter event-free interval (median, 8 v 24 months;
      P < .0001) and overall survival (median, 28 v 77 months; P < .0001). In both
      subtypes, however, patients with less than two residual lymphoma manifestations
      in remission experienced a relatively good prognosis with an estimated 5-year
      survival of greater than 60% for MCL and greater than 75% for FCL. CONCLUSION:
      MCL and FCL differ substantially in their features of presentation, response to
      chemotherapy, and long-term prognosis. The extent of residual disease after
      completion of chemotherapy discriminates patients with different prognosis and
      may be used for the stratification of postremission strategies.

PMID- 9586917
TI  - BRCA1 and BRCA2: from molecular genetics to clinical medicine.
AB  - Inherited susceptibility to breast cancer has been an area of intense
      investigation for the past 10 years. Early work focused on identifying modes of
      transmission, which culminated in the identification of chromosome 17q12-21 as
      the first human genomic region that harbored an autosomal dominant susceptibility
      gene for breast cancer (BRCA1) in 1990. BRCA1 was subsequently identified and was
      followed shortly by the identification of BRCA2. Research in the past 3 years has
      elucidated much about the mutation spectrum and mutation frequency of these genes
      in specific populations and is beginning to identify potential functions. Whereas
      progress in this area has been rapid and much is now known about inherited
      susceptibility to breast cancer, much more needs to be done to make these
      discoveries useful in the diagnosis, treatment, and ultimately, the prevention of
      breast cancer.

PMID- 9586914
TI  - Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.
AB  - PURPOSE: Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin
      are two of the most active single agents used in the treatment of non-small-cell
      lung cancer (NSCLC). A recently reported phase I study of the combination of
      docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3
      weeks for subsequent phase II study. PATIENTS AND METHODS: Eligible patients were
      aged 18 to 75 years with a World Health Organization (WHO) performance status <
      or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally
      advanced NSCLC proven histologically or cytologically. Patients were not
      permitted to have received prior chemotherapy, extensive radiotherapy, or any
      radiotherapy to the target lesion and must have had measurable disease.
      Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic
      antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was
      given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in
      500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication
      included ondansetron, dexamethasone, promethazine, and standard hyperhydration
      with magnesium supplementation. RESULTS: A total of 47 patients, two thirds of
      whom had metastatic disease, were entered onto this phase II study. The majority
      of patients were male (72%) and of good (WHO 0 to 1) performance status (85%).
      All 47 patients were assessable for toxicity and 36 were for response. Three
      patients were ineligible and eight (17%) discontinued treatment because of
      significant toxicity. In assessable patients, the overall objective response rate
      was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease,
      and 25% progressive disease. On an intention-to-treat analysis, the objective
      response rate was 29.8%. Median survival was 9.6 months and estimated 1-year
      survival was 33%. Significant (grade 3/4) toxicities included nausea (26%),
      hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection
      (13%). One patient experienced National Cancer Institute (NCI) grade 3
      neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and
      occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one
      patient). Significant (grade 3/4) abnormalities of magnesium levels were common
      (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection
      in 11%, contributing to two treatment-related deaths. No neutropenic
      enterocolitis or severe fluid retention was reported. CONCLUSION: Compared with
      other active regimens used in this setting, the combination of docetaxel and
      cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile
      to other combination regimens.

PMID- 9586919
TI  - Cancer care during the last phase of life.
AB  - EXECUTIVE SUMMARY: The American Society of Clinical Oncology (ASCO) believes that
      it is the oncologists' responsibility to care for their patients in a continuum
      that extends from the moment of diagnosis throughout the course of the illness.
      In addition to appropriate anticancer treatment, this includes symptom control
      and psychosocial support during all phases of care, including those during the
      last phase of life. In an effort to assure that all patients and their families
      have access to optimal care at the end of life, ASCO firmly believes it is
      essential to emphasize a humane system of cancer care based on the following
      principles: Cancer care is centered around the longstanding and continuous
      relationship between the primary oncologist or other physician with training and
      interest in end-of-life care and the patient; Cancer care is responsive to the
      patient's wishes and to the parents' wishes if the patient is a child; Cancer
      care is based on truthful, sensitive, empathic communication with the patient,
      and in the case of pediatric patients, that care is both family centered as well
      as child focused; and Cancer care optimizes quality of life throughout the course
      of an illness through meticulous attention to the myriad physical, spiritual, and
      psychosocial needs of the patient and family. To reach these goals, ASCO has
      identified numerous obstacles that hinder delivery of high-quality end-of-life
      care and offers recommendations for improvements. ASCO is committed to informing
      its membership and the public about the significant barriers to optimal care at
      the end of life, and advocating legislative and regulatory changes that will
      eliminate these barriers.

PMID- 9586921
TI  - Radiation therapy for stage II seminoma.

PMID- 9586913
TI  - New combination of the old drugs for elderly patients with small-cell lung
      cancer: a phase II study of the PAVE regimen.
AB  - PURPOSE: A regimen of cisplatin, doxorubicin, vincristine, and etoposide (PAVE)
      was designed for patients with small-cell lung cancer (SCLC) who were older than
      65 years, with the following objectives compared with standard chemotherapy
      regimens: maintain efficacy, diminish toxicity, enhance compliance, and improve
      chemotherapy administration convenience at an acceptable cost. PATIENTS AND
      METHODS: The PAVE regimen consisted of cisplatin 30 mg/m2 intravenously (i.v.)
      day 1; doxorubicin 40 mg/m2 i.v. day 1; vincristine 1.0 mg/m2 i.v. day 1; and
      etoposide 100 mg/m2 i.v. day 1 and orally days 3 and 5. Cycles were repeated
      every 3 weeks for four cycles. Patients with limited-stage disease and selected
      patients with extensive-stage disease received thoracic irradiation delivered
      concurrently with etoposide-cisplatin (EP) at the time of the second chemotherapy
      cycle. RESULTS: Sixty-six eligible patients were treated, which included 25
      patients with limited-stage disease and 41 patients with extensive-stage disease.
      Median survival was 70 weeks and 5-year survival was 25% for limited-stage
      disease. Median survival was 46 weeks for extensive-stage disease. Only one
      treatment-related death occurred and severe toxicity was infrequent. The median
      delivered dose-intensity was according to protocol and the mean delivered total
      dose was 80% of intended. CONCLUSION: The treatment outcome achieved with PAVE in
      a phase II study of elderly patients compared favorably with published results of
      standard regimens in patient populations with better prognostic factors. Because
      the PAVE regimen can be delivered with good compliance, has acceptable toxicity,
      and is associated with logistic advantages compared with standard regimens, this
      protocol is suitable for further investigative trials in elderly patients with
      SCLC.

PMID- 9586924
TI  - The supraorbital keyhole approach to supratentorial aneurysms: concept and
      technique.
AB  - BACKGROUND: Anterior surgical approaches to the base of the brain have always
      required relatively large craniotomies, most larger than the lesion itself.
      Especially in aneurysm surgery, the size of the lesion is not always
      proportionate to the extent of brain exposure. The improvement of surgical
      techniques and diagnostic imaging, as well as the introduction of neuroendoscopy
      and new surgical instruments, enable us now to treat various intracranial lesions
      through small keyholes. In particular, cerebral aneurysms, because of their
      anatomic characteristics, are apt to be treated by the keyhole approach. The
      supraorbital keyhole approach has the broadest field of indications, although its
      technical aspects have not yet been evaluated. METHODS: The concept and technique
      of the supraorbital keyhole approach are presented in detail. We conducted a
      retrospective study in which we evaluated the technical aspects of the
      supraorbital keyhole approach considering the indications, limitations, and
      complications of this approach as well as new instrumentation in surgery of
      supratentorial aneurysms. RESULTS: The use of 139 supraorbital keyhole approaches
      for 197 aneurysms is described. Multiple aneurysms have been treated by one
      approach in 38 patients. Clipping of the aneurysm was performed in 94% and
      wrapping in 6% of patients. Eighteen aneurysms were contralateral to the
      approach. In four patients, intraoperative accidental aneurysm rupture occurred.
      There were no approach-related complications. CONCLUSIONS: The supraorbital
      keyhole approach offers equal surgical possibilities with less intraoperative
      accidental rupture and less approach-related morbidity as conventional approaches
      in the treatment of supratentorial aneurysms.

PMID- 9586918
TI  - Pregnancy after bone marrow transplantation.
AB  - PURPOSE: To evaluate the occurrence of pregnancy after bone marrow
      transplantation (BMT). DESIGN: Medline literature review of reported pregnancies
      in the BMT population published in the English language. RESULTS: Multiple case
      reports and a few series studies showed more than 250 offspring from BMT
      recipients. CONCLUSION: BMT patients receive high-dose chemotherapy and often
      radiation, as well. These agents are associated with gonadal dysfunction and the
      fertility of patients after BMT is of concern because BMT patients are often
      young people who wish to resume a normal quality of life, which for many patients
      involves the desire to have children. Our experience with the successful
      pregnancy of one of our BMT patients led to the investigation of reported cases
      that showed numerous other births. The issue of counseling BMT patients about
      fertility, pregnancy complications, and potential birth defects is becoming
      increasingly complex and warrants further investigation.

PMID- 9586928
TI  - Intradural spinal hibernoma: case report.
AB  - BACKGROUND: Hibernoma is a rare, benign tumor arising from vestigial remnants of
      brown adipose tissue. It usually affects muscle and subcutaneous tissue and is
      asymptomatic and slow growing. METHODS: A review of the worldwide literature
      contains about 110 cases of hibernomas. However, only two cases (including our
      case) of hibernoma located in the intradural spine have been reported. We present
      an extremely rare case of intradural extramedullary spinal hibernoma and
      summarize the magnetic resonance imaging (MRI) findings of the lesion. CASE
      DESCRIPTION: A 35-year-old woman suffered from motor weakness and numbness of the
      left upper extremity. Cervical spinal MRI revealed an intradural extramedullary
      mass at C7. She underwent surgery via the posterior approach and the lesion was
      completely removed. Histopathologic examination showed multivacuolated cells with
      centrally placed nuclei, and the diagnosis of hibernoma was made. CONCLUSIONS:
      Because the CT and MRI findings of hibernoma are almost same as those of other
      lipomatous tumors, a surgical specimen of this tumor is necessary to establish
      the correct diagnosis. Early diagnosis and total resection are necessary as some
      cases showed malignant features or rapid growth. Etiologically, the tumor may
      have developed by the ectopic growth or migration of adipose tissue.

PMID- 9586922
TI  - Differences in toxicity findings for antiestrogens.

PMID- 9586923
TI  - Direct surgical management of large bulbous and giant aneurysms involving the
      paraclinoid segment of the internal carotid artery: report of 29 cases.
AB  - BACKGROUND: Twenty-nine patients with large bulbous and giant aneurysms of the
      paraclinoid segment of the internal carotid artery (ICA) were operated on, using
      Dolenc's combined epi- and subdural approach, between 1985 and 1994. Ages ranged
      from 25 to 79 (83% female; 17% male). METHODS: Proximal control was established
      in all patients through either an extracranial or petrous carotid exposure. The
      aneurysm was approached through a wide exposure by removing the anterior clinoid
      extradural. All but one aneurysm was clipped directly. A saphenous vein graft
      from the petrous-to-supraclinoid bypass was performed in this remaining case.
      RESULTS: Surgical morbidity was assessed at 20%. One patient developed a
      postoperative subdural hematoma and remained severely disabled. Two patients
      developed permanent third nerve palsy. One patient experienced severe disabling
      cognitive deficit. One patient died from complications related to a stroke. One
      patient developed transient diabetes insipidus. Visual outcome, which was
      assessed separately, was unimproved in 50% of the cases during a follow-up period
      that averaged 7 years. CONCLUSIONS: With the development of cranial base
      procedures such as Dolenc's combined epi- and subdural approach, large and giant
      aneurysms of the paraclinoid segment can be directly clipped with acceptable
      morbidity, allowing the ICA to remain patent.

PMID- 9586925
TI  - Endovascular coil embolization of microsurgically produced experimental
      bifurcation aneurysms in rabbits.
AB  - BACKGROUND: Endovascular treatment of cerebral aneurysms is a relatively new
      method, since only a few animal models and data are available. The present
      experimental study was performed in order to establish an appropriate aneurysm
      animal model, to determine the rate of permanent occlusion, and to correlate
      radiologic and morphologic findings. METHODS: End-to-side anastomoses of both
      common carotid arteries were performed microsurgically in 53 chinchilla rabbits.
      Venous pouches were adapted into the newly created bifurcation, resulting in
      berry-shaped aneurysms comparable to those in humans with regard to size and
      hemodynamics. Platinum and tungsten coils were used for endovascular
      embolization. The embolized aneurysms were investigated radiologically and
      morphologically. RESULTS: Twenty-three carotid bifurcation aneurysms remained for
      testing endovascular therapeutic approaches. The morphologic examinations of 13
      embolized aneurysms revealed in no instance a complete obliteration, even in the
      three cases that were considered completely embolized according to angiographic
      criteria. CONCLUSIONS: The present animal model is an optimal tool for
      endovascular research. Analysis of the results of coil obliteration revealed a
      considerable discrepancy between radiologic and pathologic findings. The
      radiologic degree of aneurysm occlusion was overestimated.

PMID- 9586920
TI  - Diagnosis in oncology. Askin tumor.

PMID- 9586927
TI  - Lumbar spine lesion.

PMID- 9586926
TI  - Subarachnoid hemorrhage associated with angiographic "stenotic" or "occlusive"
      lesions in the carotid circulation.
AB  - BACKGROUND: It has been assumed that dissecting aneurysms presenting with
      subarachnoid hemorrhage (SAH) are extremely rare in the carotid circulation. This
      may be partially attributed to the difficulty in their diagnosis. The documented
      angiographic findings include arterial narrowing or occlusion. The purpose of the
      present study is to investigate the origin of SAH associated with "stenotic" or
      "occlusive" lesions, which might have been categorized into "SAH of unknown
      origin." METHODS: Between April 1984 and June 1994, 580 patients underwent
      thorough angiographic investigation to determine the origin of their nontraumatic
      SAH. Of these patients, five patients had as the only lesion suspected as the
      source of SAH a single stenosis or occlusion in the carotid circulation that was
      revealed at the first angiography performed within 48 hours following the onset.
      We detail these five patients and discuss the current strategy for the treatment
      of SAH associated with stenotic or occlusive lesions in the carotid circulation.
      RESULTS: Arterial narrowing or occlusion were located in the internal carotid
      artery (ICA) in two patients, in the middle cerebral artery (MCA) in two
      patients, and in the posterior communicating artery in one patient. Three
      patients underwent operation (circumferential wrapping with cotton gauze), and
      dissecting aneurysms were confirmed in all of them. They all attained good
      recovery without rebleeding over a long-term period. Two patients died of fatal
      rebleeding on day 8 and on day 9 while awaiting the second angiography. In one of
      the patients with ICA stenosis, autopsy revealed a lacerated ICA without a
      definite saccular aneurysm. In the last patient with M2 occlusion, dissecting
      aneurysm was strongly suspected from the clinical course. CONCLUSION: To prevent
      early fatal rebleeding, exploratory craniotomy for angiographic stenotic and
      occlusive lesions associated with SAH may be justified if all underlying
      conditions are met, because they may likely include dissecting aneurysms: (1)
      single stenotic or occlusive, (2) surgically accessible, and (3) consistent with
      the localization of SAH from CT scan.

PMID- 9586929
TI  - Hypertrophied cauda equina presenting as intradural mass: case report and review
      of literature.
AB  - BACKGROUND: Hereditary motor and sensory neuropathy types I and III usually lead
      to enlargement of peripheral nerves. Rarely, spinal nerve roots may also be
      involved, leading to radiculopathy and/or myelopathy. METHODS: This 44-year-old
      man with back and lower extremity radicular pain and distal lower extremity
      weakness and numbness was found to have a nonenhancing intradural mass that
      caused a nearly complete myelographic block from L1-L4. He underwent a
      decompressive laminectomy with intradural exploration. RESULTS: Hypertrophic but
      otherwise normal-looking nerve roots were observed. Subsequent electrodiagnostic
      testing and sural nerve biopsy confirmed that this patient had a previously
      unsuspected hereditary motor and sensory neuropathy (HMSN). His pain resolved,
      but at latest follow-up his weakness and numbness persisted. CONCLUSIONS:
      Nonenhancing spinal intradural mass lesions may represent enlarged nerve roots,
      which have a number of potential etiologies. Electrodiagnostic studies and
      peripheral nerve biopsy are instrumental in establishing the diagnosis of HMSN.

PMID- 9586940
TI  - Are our meetings of value?

PMID- 9586936
TI  - Isolated trigeminal nerve metastases from breast cancer: an unusual cause of
      trigeminal mononeuropathy.
AB  - BACKGROUND: Mononeuropathy of a cranial nerve caused by brain metastases rarely
      occurs in patients with a malignant neoplasm. Even after the development of
      computed tomography (CT) and magnetic resonance imaging (MRI), few cases of brain
      metastases resulting in trigeminal mononeuropathy have been reported. We report a
      case of trigeminal mononeuropathy caused by a brain metastases that was detected
      on CT and MRI preoperatively, and was successfully treated by microsurgery and
      radiation. CASE DESCRIPTION: A 49-year-old woman with a history of breast cancer
      complained of right facial pain. CT and MRI revealed a brain tumor in the right
      Meckel's cave and cerebellopontine angle. She underwent surgery, and the
      diagnosis was metastatic breast cancer. No recurrence was detected on MRI
      performed 2 years after the resection and radiation of the tumor. CONCLUSIONS:
      Most of the reported cases of brain metastases causing a mononeuropathy occurred
      before the availability of CT; the mononeuropathy was diagnosed by neurologic or
      postmortem examination. Even after the development of CT and MRI, few cases of
      brain metastases resulting in trigeminal mononeuropathy have been reported. If
      such patients do not manifest symptoms of brain metastases other than the
      mononeuropathy, it is difficult to make the correct diagnosis without CT and MRI.
      Physicians must be aware of mononeuropathy as an uncommon presenting symptom of
      brain metastases.

PMID- 9586930
TI  - Fatal spontaneous spinal epidural hematoma following thrombolysis for myocardial
      infarction.
AB  - BACKGROUND: This is the first communication of a fatal spontaneous spinal
      epidural hematoma following thrombolysis. CLINICAL PRESENTATION: Spine pain may
      precede neurologic deterioration by many hours. The diagnosis can be accurately
      made with axial computed tomography (CT) of the involved spinal segment.
      TREATMENT: Emergency surgery is the treatment for this condition, but conditions
      such as the acute stage of a myocardial infarction or intraoperative bleeding
      difficulties due to iatrogenic coagulopathy, the degree of preoperative
      neurologic deficit, and the timing of surgery must be cautiously considered.
      CONCLUSIONS: Neurosurgeons will be faced with another devastating complication of
      thrombolytic therapy, as long as the available drugs are being used. Early
      clinical suspicion and availability of CT or magnetic resonance imaging for
      prompt diagnosis are essential to initiate appropriate medical therapy and timely
      surgery. New strategies must include the development of completely fibrin
      specific thrombolytics and drugs that may rapidly reverse the systemic and local
      clotting disorder.

PMID- 9586934
TI  - Giant cell tumor of the sphenoid bone: long-term follow-up of two cases after
      chemotherapy.
AB  - BACKGROUND: Giant cell tumors rarely occur in the sphenoid bone. When they do
      occur in the base of the skull, surgical treatment is frequently difficult and
      therefore, the use of adjuvant therapy is important. However, there remains no
      optimal management regimen for giant cell tumors of the sphenoid bone. CASE
      DESCRIPTION: Two cases of a giant cell tumor involving the sphenoid bone that
      responded well to chemotherapy using adriamycin after a partial removal of the
      tumor are presented. In the first patient, the tumor was partially removed via a
      transcranial subfrontal approach and a transnasal transsphenoidal approach. In
      the second patient, the tumor was partially removed through a transcranial
      subfrontal approach. Both tumors demonstrated histologic features typical of
      giant cell tumors. The patients subsequently received adjuvant chemotherapy using
      adriamycin alone in the first patient, and chemotherapy combined with
      radiotherapy in the second patient. Partial regression of the tumors was later
      confirmed on a computed tomography (CT) scan after chemotherapy. In both
      patients, tumors have been stable for more than 12 years despite an incomplete
      removal of the tumors. CONCLUSION: Based on the above findings, postoperative
      adjuvant chemotherapy using adriamycin may be effective for incompletely resected
      giant cell tumors of the sphenoid bone.

PMID- 9586931
TI  - Fenestration of porencephalic cysts to the lateral ventricle: experience with a
      new technique for treatment of seizures.
AB  - BACKGROUND: Porencephalic cysts are brain cavities resulting from perinatal
      vascular occlusion and are commonly associated with severe neurological deficits
      and medically intractable epilepsy. Thirty-seven children presenting to the
      University of Munster with intractable seizures because of a porencephalic cyst
      were treated by uncapping and fenestration of these cysts to the lateral
      ventricle between 1978 and 1992. We conducted the following study to determine
      the efficacy and safety of the uncapping and fenestration procedure for the
      treatment of seizures. METHODS: We reviewed all cases retrospectively and
      assessed the outcome of these patients with regard to seizures, paresis, and
      perioperative complications. RESULTS: Of 37 children, 23 (62%) were seizure-free
      postoperatively. Nine patients (24%) had a reduction of seizures and five
      children (14%) remained unchanged. Of 30 patients with preoperative hemiparesis,
      11 (30%) improved after the operation. The leading postoperative problem was a
      subcutaneous/subgaleal cushion of CSF, which affected 12 children (12 of 37). A
      dural patch covering the iatrogenic dural defect could not prevent or reduce
      postoperative CSF leakage, but prolonged the postoperative fever period.
      Postoperative fever occurred in 36 children (36 of 37) and was caused by an
      aseptic meningitis. CONCLUSIONS: Children with intractable seizures and
      porencephalic cysts benefit from uncapping and cyst fenestration to the lateral
      ventricle. Concomitant perioperative complications are mild and are easily
      treated.

PMID- 9586935
TI  - Nasopharyngeal carcinoma presenting as an intracranial abscess.
AB  - BACKGROUND: There are many conditions related to brain abscess. Brain abscesses
      resulting from nasopharyngeal carcinoma is rare. It is unusual for an
      intracranial abscess to appear as the initial clinical presentation of
      nasopharyngeal carcinoma. CASE REPORT: A 43-year-old male patient suffering from
      nasopharyngeal carcinoma with the initial manifestation of an intracranial
      abscess without symptoms and signs suggestive of the primary nasopharyngeal
      carcinoma is reported. The diagnosis was particularly elusive and was not made
      until the third admission. CONCLUSION: Although it is rare, intracranial abscess
      should be considered as one of the possible manifestations of nasopharyngeal
      carcinoma.

PMID- 9586937
TI  - Acute hydrocephalus after subarachnoid hemorrhage.
AB  - BACKGROUND: Acute hydrocephalus as a consequence of subarachnoid hemorrhage is a
      relatively frequent problem. It is associated with more neurologic impairment and
      mortality than subarachnoid hemorrhage without hydrocephalus. A review of the
      literature was done to determine its frequency of presentation, the associated
      causes of morbidity and mortality, its clinical presentation, and treatment
      options. METHODS: A search was done through the Med-Line system to obtain
      pertinent literature of the last 10 years. Articles before this date were
      obtained from references from the original search. RESULTS: Acute hydrocephalus
      is present in 20% of patients with subarachnoid hemorrhage. One third of them may
      be asymptomatic on admission; 50% of those who have clinical hydrocephalus
      recover spontaneously within the first 24 h. The presence of acute hydrocephalus
      after subarachnoid hemorrhage is associated with additional morbidity and higher
      mortality secondary to rebleeding, to cerebral infarction or to shunt infection.
      Once hydrocephalus develops, ventricular size is not related to the clinical
      status of the patient, nor to the associated complications. CONCLUSIONS: If a
      patient presents with subarachnoid hemorrhage accompanied by acute hydrocephalus
      and preserved level of consciousness, he/she should be carefully observed for the
      first 24 h. If deterioration of consciousness ensues and is not attributable to
      rebleeding or metabolic causes, ventriculostomy should be performed. If a patient
      presents with subarachnoid hemorrhage accompanied by acute hydrocephalus and
      depressed level of consciousness ventriculostomy should be immediately placed.
      After ventriculostomy, intracranial pressure should be maintained above 15 mm Hg
      to prevent rebleeding. Prophylactic antibiotics and long subcutaneous catheters
      should be used to avoid shunt infections.

PMID- 9586933
TI  - Intracranial facial nerve neurinoma: surgical strategy of tumor removal and
      functional reconstruction.
AB  - BACKGROUND: Three cases with intracranial facial neurinoma underwent tumor
      removal and facial nerve reconstruction with or without tympanoplasty. Surgical
      strategy for each case was tailored to: (1) the site of main tumor mass, (2) its
      extension along the facial nerve, and (3) involvement of the auditory organs.
      METHODS: Surgeries adopted in the three cases were: transpetrosal approach with
      intracranial-intratemporal facial nerve anastomosis, middle fossa and
      transmastoid approach with intratemporal facial nerve anstomosis and
      tympanoplasty, and middle fossa and transmastoid approach with intracranial
      intratemporal facial nerve anastomosis and tympanoplasty. The greater auricular
      nerve was used as the nerve graft for all three cases. RESULTS: In the follow-up
      period of 8-13 months there was no tumor recurrence; facial function was scored
      20/90 in modified May's scoring system in each case, but two are still in the
      process of functional recovery. One of the two cases who underwent tympanoplasty
      showed complete recovery of hearing within 1 month, and the other showed worsened
      hearing, which was not serviceable at 3 months postoperatively. CONCLUSION:
      Systematic surgical approach for tumor removal, facial nerve reconstruction, and
      auditory reconstruction should be considered in cases with intracranial facial
      neurinoma due to its varied clinical features.

PMID- 9586938
TI  - Antiepileptic drug review: part 2.

PMID- 9586941
TI  - Inadvertent intrathecal application of ionic contrast agent.

PMID- 9586942
TI  - Role of nitric oxide and its intracellular signalling pathways in the control of
      Ca2+ homeostasis.
AB  - Ca2+, a primary regulator of physiological functions in all cells, is involved in
      a variety of intracellular signalling pathways; control of Ca2+ homeostasis is,
      therefore, a fundamental cell activity. To this end, cells have developed a
      variety of mechanisms to ensure the buffering of Ca2+, its influx and extrusion
      from the plasma membrane, and its release/accumulation within specific
      intracellular storage compartments. Over the last few years, evidence gathered
      from a number of cell systems has indicated that one of the key messengers
      governing the overall control of Ca2+ homeostasis is nitric oxide (NO), which may
      be produced intracellularly or may originate from neighboring cells. The aim of
      the present commentary is to concentrate on the biochemical steps in Ca2+
      homeostasis that are controlled by NO and to describe what is known thus far
      concerning the molecular mechanisms of its action. Particular attention will be
      given to the effects of NO on: (i) inositol 1,4,5-trisphosphate and cyclic ADP
      ribose generation; (ii) Ca2+ release from both inositol 1,4,5-trisphosphate
      sensitive and ryanodine-sensitive Ca2+ stores; and (iii) Ca2+ influx via both
      store- and second messenger-operated Ca2+ channels. The evidence discussed here
      documents the complexity of the interactions between the Ca2+ and the NO
      signalling systems, which represent an extraordinary example of cross-talk
      operating at multiple sites and which are continuously active in the regulation
      of cytosolic Ca2+ (and NO) levels.

PMID- 9586943
TI  - Formation of N-acyl-phosphatidylethanolamines and N-acetylethanolamines: proposed
      role in neurotoxicity.
AB  - The formation of N-acyl-phosphatidylethanolamine (NAPE) and N-acylethanolamine
      (NAE), including anandamide, in mammals in relation to neurotoxicity is
      discussed. Data on the characterization of the NAPE-forming N-acyltransferase,
      the NAPE-hydrolyzing phospholipase D, and the NAE-hydrolyzing amidase are
      reviewed. We suggest that NAPE and NAE, including anandamide, are formed in
      neurons in response to the high intracellular calcium concentrations that occur
      in injured neurons, e.g. due to glutamate excitotoxicity. NAPE may have functions
      of its own besides being a precursor for NAE. The formation of both of these
      lipids may serve as a cytoprotective response, whether mediated by physical
      interactions with membranes or enzymes, or mediated by activation of cannabinoid
      receptors. This suggestion implies that NAPE and NAE may have pathophysiological
      roles in the brain. Whether these lipids also have physiological roles is
      uncertain.

PMID- 9586932
TI  - Primarily extracranial jugular foramen neurinoma manifesting with marked
      hemiatrophy of the tongue: case report.
AB  - BACKGROUND: There have been no detailed descriptions of the clinical symptoms of
      a primarily extracranial jugular foramen neurinoma (JFN), because this type of
      tumor is extremely rare. CASE DESCRIPTION: Although the 51-year-old woman
      presented with only mild complaints of dysphagia and hoarseness, neurologic
      examination revealed marked left hemiatrophy of the tongue. Although magnetic
      resonance imaging suggested a JFN, the patient's mild symptoms and normal jugular
      foramen were potentially misleading in the diagnosis of this patient. Surgical
      exploration demonstrated that the tumor originated from the extracranial portion
      of the 10th cranial nerve, extending into the jugular foramen. Subtotal resection
      ameliorated the 12th cranial nerve palsy. CONCLUSION: The authors present a case
      of a primarily extracranial JFN manifesting as a 12th nerve palsy. The clinical
      symptoms and signs produced by a tumor in this extremely rare location are
      discussed.

PMID- 9586946
TI  - Glutathione carbamoylation with S-methyl N,N-diethylthiolcarbamate sulfoxide and
      sulfone. Mitochondrial low Km aldehyde dehydrogenase inhibition and implications
      for its alcohol-deterrent action.
AB  - S-Methyl N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO) and sulfone (DETC-MeSO2)
      both inhibit rat liver low Km aldehyde dehydrogenase (ALDH2) in vitro and in vivo
      (Nagendra et al., Biochem Pharmacol 47: 1465-1467, 1994). DETC-MeSO has been
      shown to be a metabolite of disulfiram, but DETC-MeSO2 has not. Studies were
      carried out to further investigate the inhibition of ALDH2 by DETC-MeSO and DETC
      MeSO2. In an in vitro system containing hydrogen peroxide and horseradish
      peroxidase, the rate of DETC-MeSO oxidation corresponded to the rate of DETC
      MeSO2 formation. Carbamoylation of GSH by both DETC-MeSO and DETC-MeSO2 was
      observed in a rat liver S9 fraction. Carbamoylation of GSH was not observed in
      the presence of N-methylmaleimide. In in vitro studies, DETC-MeSO and DETC-MeSO2
      were equipotent ALDH2 inhibitors when solubilized mitochondria were used, but
      DETC-MeSO was approximately four times more potent than DETC-MeSO2 in intact
      mitochondria. In studies with rats, the dose (i.p. or oral) required to inhibit
      50% ALDH2 (ED50) was 3.5 mg/kg for DETC-MeSO and approximately 35 mg/kg for DETC
      MeSO2, approximately a 10-fold difference. Furthermore, maximum ALDH2 inhibition
      occurred 1 hr after DET(-MeSO administration, whereas maximal ALDH2 inhibition
      occurred 8 hr after DETC-MeSO2 dosing. DETC-MeSO is, therefore, not only a more
      potent ALDH2 inhibitor than DETC-MeSO2 in vivo, but also in vitro when intact
      mitochondria are utilized. The in vitro results thus support the in vivo
      findings. Since oxidation of DETC-MeSO can occur both enzymatically and non
      enzymatically, it is possible that DETC-MeSO2 is formed in vivo. DETC-MeSO2,
      however, is not as effective as DETC-MeSO in inhibiting ALDH2, probably because
      it has difficulty penetrating the mitochondrial membrane. Thus, even if DETC
      MeSO2 is formed in vivo from DETC-MeSO, it is the metabolite DETC-MeSO that is
      most likely responsible for the inhibition of ALDH2 after disulfiram
      administration.

PMID- 9586944
TI  - An assessment of drug-haematin binding as a mechanism for inhibition of haematin
      polymerisation by quinoline antimalarials.
AB  - Chloroquine is thought to exert its antimalarial activity by preventing the
      polymerisation of toxic haematin released during proteolysis of haemoglobin in
      the Plasmodium digestive vacuole. However, the molecular mechanisms by which this
      inhibition occurs and the universality of this mechanism for other quinoline
      antimalarials remain to be established. We demonstrate here a correlation for
      eight antimalarial quinolines between inhibition of haematin polymerisation in
      vitro and inhibition of P. falciparum growth in culture, confirming haematin
      polymerisation as the likely target of quinoline blood schizonticides.
      Furthermore, using isothermal titration microcalorimetry, a correlation was
      observed between the haematin binding constant of these compounds and their
      ability to inhibit haematin polymerisation, suggesting that these compounds
      mediate their activity through binding to haematin. It was also observed that the
      compounds bind primarily to the mu-oxo dimer form of haematin rather than the
      monomeric form. It is postulated that this binding inhibits haematin
      polymerisation by shifting the haematin dimerisation equilibrium to the mu-oxo
      dimer, thus reducing the availability of monomeric haematin for incorporation
      into haemozoin. These data reconcile the haematin polymerisation theory with the
      Fitch hypothesis, which states that chloroquine mediates its activity through
      binding to haematin.

PMID- 9586945
TI  - A comparison and analysis of several ways to promote haematin (haem)
      polymerisation and an assessment of its initiation in vitro.
AB  - We compared several methods for producing haematin polymerisation at
      physiological temperatures (i.e., 37 degrees) and found that a trophozoite lysate
      mediated reaction was inappropriate for measuring compound inhibition of haematin
      polymerisation. Using this method, we obtained significantly higher IC50 values
      (concentration inhibiting haematin polymerisation by 50%) for certain compounds
      than when other methods were used, including a food vacuole lysate-mediated
      reaction. This difference was probably due to the binding of these compounds to
      cytosolic parasite proteins, as proteinase K treatment of the trophozoite lysate
      reversed this effect. The initiation of haematin polymerisation was also
      investigated using several assays. It was found that haematin polymerisation
      occurred spontaneously, in the absence of preformed haemozoin, over a period of
      several days, but that the process was more rapid when an acetonitrile extract of
      malarial trophozoites was added. This extract contained no detectable protein,
      and its activity could be replicated using an extract from uninfected
      erythrocytes and by using lipids. We therefore postulate that no protein or
      parasite-specific material is absolutely required for the initiation of haematin
      polymerisation. The formation of beta-haematin de novo using the acetonitrile
      extract is more pH-dependent than the generation of newly synthesised beta
      haematin from preformed haemozoin and cannot proceed much above pH = 6. We
      postulate that the initiation of haematin polymerisation is more sensitive to the
      equilibrium of haematin between its monomeric and mu-oxo dimer form and requires
      a higher concentration of monomer than for the elongation phase of
      polymerisation.

PMID- 9586948
TI  - Inhibition of the 1,25-dihydroxyvitamin D3-induced increase in vitamin D receptor
      (VDR) levels and binding of VDR-retinoid X receptor (RXR) to a direct repeat (DR)
      3 type response element by an RXR-specific ligand in human keratinocyte cultures.
AB  - The biological active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3),
      mediates most of its actions through the intracellular vitamin D receptor (VDR).
      VDR binds to vitamin D responsive elements (VDREs) in the promoter region of
      responsive genes and regulates transcription. Usually the VDREs consist of a
      direct repeat of two hexanucleotides spaced by three nucleotides (DR-3), to which
      VDR preferentially binds as a heterodimer with the retinoid X receptor (RXR). In
      the present study, we examined the effect of 1,25(OH)2D3 and a specific ligand
      for RXR, CD2809, on VDR and RXR levels in cultured human keratinocytes and on the
      binding of RXR-VDR to a DR-3 type response element. Incubation with 1,25(OH)2D3
      increased VDR levels as determined by Western blotting, increased VDR-RXR binding
      to a DR-3 type response element as determined by the electromobility shift assay
      (EMSA), and induced the 25-OH-D3 24-hydroxylase (24-hydroxylase) gene, containing
      a DR-3 type response element. CD2809 caused a slight decrease in RXRalpha levels,
      but had no effect on VDR levels. Addition of both CD2809 and 1,25(OH)2D3
      decreased VDR levels as well as the VDR-RXR binding levels to the DR-3 type
      response element, compared to 1,25(OH)2D3 alone. In conclusion, an RXR-specific
      ligand interferes with the 1,25(OH)2D3-induced stimulation of VDR levels and VDR
      RXR binding to DNA in keratinocyte cultures. It is therefore possible that RXR
      specific ligands may counteract certain biological actions of vitamin D3.

PMID- 9586947
TI  - Role of human liver P450s and cytochrome b5 in the reductive metabolism of 3'
      azido-3'-deoxythymidine (AZT) to 3'-amino-3'-deoxythymidine.
AB  - Our laboratory has shown that human liver microsomes metabolize the anti-HIV drug
      3'-azido-3'-deoxythymidine (AZT) via a P450-type reductive reaction to a toxic
      metabolite 3'-amino-3'-deoxythymidine (AMT). In the present study, we examined
      the role of specific human P450s and other microsomal enzymes in AZT reduction.
      Under anaerobic conditions in the presence of NADPH, human liver microsomes
      converted AZT to AMT with kinetics indicative of two enzymatic components, one
      with a low Km (58-74 microM) and Vmax (107-142 pmol AMT formed/min/mg protein)
      and the other with a high Km (4.33-5.88 mM) and Vmax (1804-2607 pmol AMT
      formed/min/mg). Involvement of a specific P450 enzyme in AZT reduction was not
      detected by using human P450 substrates and inhibitors. Antibodies to human
      CYP2E1, CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP2A6 were also without effect on
      this reaction. NADH was as effective as NADPH in promoting microsomal AZT
      reduction, raising the possibility of cytochrome b5 (b5) involvement. Indeed, AZT
      reduction among six human liver samples correlated strongly with microsomal b5
      content (r2 = 0.96) as well as with aggregate P450 content (r2 = 0.97). Upon
      reconstitution, human liver b5 plus NADH:b5 reductase and CYP2C9 plus NADPH:P450
      reductase were both effective catalysts of AZT reduction, which was also
      supported when CYP2A6 or CYP2E1 was substituted for CYP2C9. Kinetic analysis
      revealed an AZT Km of 54 microM and Vmax of 301 pmol/min for b5 plus NADH:b5
      reductase and an AZT Km of 103 microM and Vmax of 397 pmol/min for CYP2C9 plus
      NADPH:P450 reductase. Our results indicate that AZT reduction to AMT by human
      liver microsomes involves both b5 and P450 enzymes plus their corresponding
      reductases. The capacity of these proteins and b5 to reduce AZT may be a function
      of their heme prothestic groups.

PMID- 9586950
TI  - Action of 21-aminosteroid U74006F as an antioxidant against lipid peroxidation.
AB  - The dynamics of the action of the 21-aminosteroid U74006F as an antioxidant
      against lipid peroxidation were studied in organic solution and membranes. It was
      confirmed that the reactivities of this compound toward stable phenoxyl radical
      and peroxyl radical were quite low. In fact, U74006F did not exert appreciable
      antioxidant effect against the free radical-driven oxidation of methyl linoleate
      in acetonitrile solution. However, it suppressed the oxidation of
      phosphatidylcholine liposomal membranes into which it was incorporated in a
      concentration-dependent manner. The 21-aminosteroid U74006F did not exert any
      sparing effect on the rate of alpha-tocopherol consumption in the oxidation of
      methyl linoleate in solution, but when they were simultaneously incorporated into
      the membrane, U74006F spared alpha-tocopherol and exerted a synergistic effect
      against the oxidation of liposomal membranes. This suggests that lipophilic
      U74006F acts as an antioxidant against lipid peroxidation through a
      physicochemical and not a pure chemical mechanism, and that a physical
      interaction with the liposomal membrane may facilitate the inhibition of lipid
      peroxidation with U74006F.

PMID- 9586949
TI  - Curcumin (Diferuloylmethane) inhibition of tumor necrosis factor (TNF)-mediated
      adhesion of monocytes to endothelial cells by suppression of cell surface
      expression of adhesion molecules and of nuclear factor-kappaB activation.
AB  - Recruitment of leukocytes by endothelial cells and their subsequent migration
      from the vasculature into the tissue play major roles in inflammation. In the
      present study, we investigated the effect of curcumin, an antiinflammatory agent,
      on the adhesion of monocytes to human umbilical vein endothelial cells (EC).
      Treatment of EC with tumor necrosis factor (TNF) for 6 hr augmented the adhesion
      of monocytes to EC, and this adhesion was due to increased expression of
      intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Pretreatment of
      EC for 1 hr with curcumin completely blocked their adhesion to monocytes, as well
      as the cell surface expression of ICAM-1, VCAM-1, and ELAM-1 in EC. Although
      curcumin inhibited adhesion even when administered 1 hr after TNF treatment,
      maximum inhibition occurred when added either 1 hr before or at the same time as
      TNF. As the induction of various adhesion molecules by TNF requires activation of
      the transcription factor NF-kappaB, the effect of curcumin on the activation of
      this factor in the EC was also investigated. A 30-min treatment with TNF
      activated NF-kappaB; the activation was inhibited in a concentration-dependent
      manner by pretreatment with curcumin, indicating that NF-kappaB inhibition may
      play a role in the suppression of expression of adhesion molecules in EC. Our
      results demonstrate that the antiinflammatory properties of curcumin may be
      attributable, in part, to inhibition of leukocyte recruitment.

PMID- 9586951
TI  - Inhibition of drug-naive and -resistant leukemia cell proliferation by low
      molecular weight thiols.
AB  - The aim of these studies was to investigate the ability of cysteamine and its
      congeners to arrest the proliferation of leukemic cells and to determine the
      physico-chemical properties responsible for this ability. Fifteen low molecular
      weight thiol-bearing compounds were shown to arrest the proliferation of CCRF-CEM
      cells and a methotrexate-resistant subline, with IC50 values between 10(-5) and
      10(-4) M. Cysteamine arrested proliferation by slowing the passage of cells
      through S phase. These cells subsequently resumed cycling, although a proportion
      went on to die by apoptosis. The antiproliferative action of cysteamine was shown
      to depend, in part, on H2O2 production. This ability to generate peroxide is
      shared by many thiol compounds, and molecular modeling indicated that thiol
      groups were required for the antiproliferative actions of the congeners of
      cysteamine. Molecular modeling also revealed that the most efficacious
      antiproliferative agents were those that had their amino acid and thiol moieties
      separated by an intramolecular distance of 3.17 to 5.9 A, as exemplified by WR
      1065 and the aminothiophenols. These findings indicate that thiol-bearing
      compounds may have some efficacy in the treatment of drug-naive and -resistant
      leukemia cells.

PMID- 9586952
TI  - Comparison of the in vitro cytotoxicity of hydroxylamine metabolites of
      sulfamethoxazole and dapsone.
AB  - The differential incidence of adverse drug reactions (ADR) between trimethoprim
      sulfamethoxazole and dapsone might be explained, in part, by differences in the
      inherent toxicity of the hydroxylamine metabolites of sulfamethoxazole and
      dapsone. To test this hypothesis, the in vitro cytotoxicities of sulfamethoxazole
      hydroxylamine, dapsone hydroxylamine, and monoacetyldapsone hydroxylamine were
      compared using peripheral blood mononuclear cells (PBMC) from healthy volunteers.
      After 3 hr of exposure to hydroxylamine metabolites, PBMC were washed thoroughly
      to remove residual hydroxylamine, and viability was assessed 16 hr later by
      determination of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT) conversion. A concentration-dependent toxicity was observed with each
      hydroxylamine metabolite. While dapsone hydroxylamine and monoacetyldapsone
      hydroxylamine were not significantly different, both showed significantly greater
      cytotoxic potency than sulfamethoxazole hydroxylamine (P < 0.05). This
      differential potency was not a function of differential stability in aqueous
      medium and was maintained over time. The effects of red blood cells (RBC),
      impermeable RBC "ghosts," and RBC lysate on hydroxylamine-induced cytotoxicity
      were determined using a two-compartment dialysis system. Amelioration of
      hydroxylamine-dependent cytotoxicity occurred when RBC were included in PBMC
      incubations. This apparent detoxifying effect was markedly greater using RBC
      lysate in comparison with impermeable "ghosts" (P < 0.05). No difference in
      detoxification was observed between sulfamethoxazole hydroxylamine and
      monoacetyldapsone hydroxylamine. Differences in the inherent cytotoxicity of
      their hydroxylamine metabolites do not appear to explain the differential
      incidence of ADR between trimethoprim-sulfamethoxazole and dapsone.

PMID- 9586953
TI  - Interaction of transresveratrol with plasma lipoproteins.
AB  - Resveratrol (3,4',5-trihydroxystilbene) is a phytoalexin present in some red
      wines. Like other phenolic substances, this compound is assumed to protect
      against atherosclerosis by reducing the peroxidative degradation of low-density
      lipoproteins (LDL). The in vitro efficiency of resveratrol was found to be mainly
      due to its capacity to chelate copper, although it also scavenges free radicals.
      In this study, we examined the ability of the compound to associate with
      lipoproteins in vitro. Trans-resveratrol added to plasma was distributed between
      subsequently isolated lipoproteins with a linear dose-response curve. The
      concentrations as expressed on a protein basis increased with the order of their
      lipid content: high-density lipoproteins (HDL) < LDL < very low-density
      lipoproteins (VLDL). This finding reveals the lipophilic character of
      resveratrol. Other assays showed that resveratrol added to plasma prior to
      fractionation was, as expressed on a protein basis, more associated with
      lipoproteins (d < 1.21 g/mL) than with lipoprotein-free proteins (5.5 +/- 0.7 vs
      2.2 +/- 0.4 nmol/mg protein). On the other hand, resveratrol inhibited the
      formation of thiobarbituric acid reactive substances (TBARS) in preparations
      containing phospholipid unilamellar liposomes oxidized by the water-soluble
      radical generator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). A linear
      dose-response curve was obtained up to 30 microM when the antioxidant was added
      in the final preparation and up to 200 microM when added before preparing
      liposomes in order to facilitate its incorporation. This suggests that the
      soluble fraction of resveratrol scavenged free radicals in the aqueous phase
      before attacking PUFA and within membranes. Taken together, the present data
      support the hypothesis that resveratrol may be efficient at different sites: in
      the protein and lipid moieties of LDL and in their aqueous environment.

PMID- 9586954
TI  - Protection by organotellurium compounds against peroxynitrite-mediated oxidation
      and nitration reactions.
AB  - Diaryl tellurides effectively protect against peroxynitrite-mediated oxidation of
      dihydrorhodamine 123 (DHR), hydroxylation of benzoate, and nitration of 4
      hydroxyphenylacetate (HPA). Bis(4-aminophenyl) telluride offered the most
      efficient protection against oxidation of DHR induced by peroxynitrite.
      Protection by this compound was approximately 3 times more effective than that
      afforded by its selenium analog, bis(4-aminophenyl) selenide, and 11 times more
      effective than selenomethionine. When peroxynitrite was infused to maintain a
      steady-state concentration, bis(4-aminophenyl) telluride in the presence of GSH,
      but neither bis(4-aminophenyl) telluride nor GSH alone, effectively inhibited the
      peroxynitrite-mediated hydroxylation of benzoate. The inhibition of nitration was
      most pronounced using bis(4-hydroxyphenyl) telluride, and this compound was ca. 3
      times more effective than selenomethionine. Bis(4-aminophenyl) telluride also
      protected proteins in lysates from human skin fibroblasts from peroxynitrite
      mediated nitration of tyrosine residues more effectively than selenomethionine.
      These data establish a potential biological or pharmacological role of
      organotellurium compounds in the defense against peroxynitrite.

PMID- 9586955
TI  - Regional distribution of individual forms of cytochrome P450 mRNA in normal adult
      human brain.
AB  - The cytochromes P450 are a large family of haemoproteins which have a major role
      in the oxidative metabolism of a wide range of xenobiotics and some endogenous
      compounds. In this study the presence of individual members of the CYP1, CYP2 and
      CYP3 P450 families has been investigated by reverse transcriptase polymerase
      chain reaction in different regions of normal human brain consisting of frontal
      and temporal cortices, mid brain, cerebellum, pons and medulla. All the P450s
      were identified in specific regions of brain with CYP1A1 and CYP2C being the most
      frequently expressed forms of P450. Sequencing identified the CYP2C PCR product
      as CYP2C8. This study indicates that individual P450 mRNAs are present in human
      brain and are found in specific brain regions. The distribution of individual
      P450s in different regions of human brain is likely to be highly important in
      determining the response of the brain to toxic foreign compounds.

PMID- 9586957
TI  - Clomiphene analogs with activity in vitro and in vivo against human breast cancer
      cells.
AB  - Six hundred triphenylethylenes were assayed for antiproliferative activity
      against MCF-7, LY2, and MDA-MB-231 breast cancer cells using sulforhodamine B dye
      to measure proliferation. Here we report on just 63 of the compounds, mostly
      clomiphene analogs, with substitutions on the alpha' or beta ring, at the vinyl
      position or in the side chain, of which 23 were active, as defined by
      antiproliferation IC50 values < or =1 microM. Activity profiles showed that 23
      and 11 analogs were active toward MCF-7 and LY2, respectively, but none were
      active against MDA-MB-231. The IC50 values of tamoxifen were 2.0 microM against
      MCF-7 and 7.5 microM against LY2 and MDA-MB-231. Estradiol reversed
      antiproliferative activities of several E isomers but not their Z isomer
      counterparts. Clomiphene side chain analogs 46 [(E)-1-butanamine, 4-[4-(2-chloro
      1,2-diphenylethenyl) phenoxy]-N,N-diethyl-dihydrogen citrate (MDL 103,323)] and
      57 [(E)-N-[p-(2-chloro-1,2-diphenylvinyl) phenyl]-N,N-diethylethylenediamine
      dihydrogen citrate (MDL 101,986)] were 4- to 5-fold more effective than
      tamoxifen. Methylene additions up to (-CH2-)12 in the clomiphene side chain
      showed that analog 46 [(-CH2-)4 side chain] had maximal antiproliferative
      activity, binding affinity, and inhibition of transcription of an estrogen
      response element luciferase construct in transfected MCF-7 cells. Intraperitoneal
      administration of 46 or 57 inhibited progression of MCF-7 breast tumor xenografts
      in nude mice with ED50 values of <0.02 mg/mouse/day. Both analogs may hold
      promise for treating ER positive breast cancer and are of interest for further
      development.

PMID- 9586956
TI  - Inhibition of CYP1A1-dependent activity by the polynuclear aromatic hydrocarbon
      (PAH) fluoranthene.
AB  - Polynuclear aromatic hydrocarbons (PAHs) are ubiquitous environmental
      contaminants, and recently bioassay-based induction studies have been used to
      determine exposures to complex mixtures of PAHs. Induction of CYP1A1-dependent
      activity in H4IIE rat hepatoma cells has been used extensively as a bioassay for
      halogenated aromatic hydrocarbons and more recently for PAHs. Fluoranthene (FL)
      is a prevalent PAH contaminant in diverse environmental samples, and FL did not
      induce CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity
      significantly in H4IIE cells. However, in cells cotreated with 2 x 10(-5) M FL
      plus the potent inducers 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or
      benzo[k]fluoranthene (BkF) (2 x 10(-8) M), there was a significant decrease in
      EROD activities. Furthermore, treatment of TCDD-induced rat microsomes with FL
      caused an 80% decrease in EROD activity. Studies showed that FL did not affect
      induction of CYP1A1 protein or mRNA levels in H4IIE cells, and analysis of enzyme
      inhibition data using microsomal CYP1A1 indicated that FL noncompetitively
      inhibited CYP1A1-dependent activity. 32P-Postlabeling revealed no significant FL
      DNA adduct formation in H4IIE cells treated with FL. However, in cells cotreated
      with FL plus BkF or benzo[a]pyrene (BaP), certain PAH-DNA adducts were induced 2
      fold. This study demonstrated that FL is an inhibitor of CYP1A1-dependent enzyme
      activity in rat hepatoma H4IIE cells and that the genotoxic potency of some
      carcinogenic PAHs may be modulated by FL in mixtures containing relatively high
      levels of this compound.

PMID- 9586958
TI  - Evidence for distinct kinase-mediated pathways in gadd gene responses.
AB  - We have evaluated the role of various protein kinases on the induction of the
      gadd (growth arrest and DNA damage inducible) genes, using a panel of protein
      kinase inhibitors. Our data indicate that three different stress response
      pathways mediating gadd gene induction are most likely regulated by different
      protein kinases or combinations of protein kinases. The protein kinase inhibitor
      staurosporine and the temperature sensitive (ts) p34cdc2 mutant reduced induction
      by the alkylating agent methylmethane sulfonate (MMS) of the rodent gadd45 and
      gadd153 genes. However, staurosporine had no effect of the ionizing radiation
      (IR) induction of the human GADD45. Caffeine and 2-aminopurine, on the other
      hand, completely blocked this IR induction. Suramin, an antitumor drug that
      interferes with the interaction of growth factors with their receptors, inhibited
      the UV radiation induction of GADD45 and GADD153 but had no effect on the MMS and
      IR pathways. Elevated expression of gadd45 by medium depletion (starvation) was
      partially reduced by the addition of either genistein or tyrphostin, two protein
      tyrosine kinase inhibitors, while gadd153 was affected by tyrphostin only. Two
      inhibitors acting preferentially on cAMP-dependent protein kinase (PKA), N-[2
      (methylamino)ethyl]-5-isoquinolinesulfonamide, HCl (H8) and protein kinase
      inhibitor (PKI), also had a moderate effect on the medium depletion-induced
      levels of both gadd genes. Thus, these varied effects of inhibitors on gadd gene
      responses point to important differences in the pathways controlling these
      responses.

PMID- 9586960
TI  - Agonist-induced desensitization of A2B adenosine receptors.
AB  - Agonist-induced desensitization has been described for the A1, A2A, and A3
      adenosine receptor subtypes of the G protein-coupled receptor superfamily.
      Desensitization of the fourth adenosine receptor subtype, the A2B adenosine
      receptor (A(2B)R), has not been studied extensively. We sought to determine
      whether the A(2B)R is subject to agonist-induced desensitization. COS 7 cells,
      which exhibit endogenous expression of the A(2B)R, and transfected CHO cells,
      which stably express a modified rat A(2B)R bearing a 5' FLAG epitope tag, were
      studied. Cyclic AMP (cAMP) responsiveness to an acute challenge was measured
      after pretreating (desensitizing) cells with the adenosine receptor agonist 5'-N
      ethylcarboxamidoadenosine (NECA). Incubation with NECA resulted in
      hyporesponsiveness to acute agonist challenge in both COS 7 and transfected CHO
      cells. Desensitized cells exhibited restoration of cAMP responses after recovery
      for 24 hr in growth medium. Choleratoxin-induced cAMP responses were preserved in
      desensitized cells, and high concentrations of NECA were unable to overcome the
      desensitization. Membrane levels of the epitope-tagged A(2B)R were assessed by
      western blot in transiently transfected COS 7 cells. The expression of epitope
      tagged A(2B)Rs was not different between control and desensitized cells. In
      northern blot analysis, levels of endogenous A(2B)R mRNA were similar in control
      and desensitized COS 7 cells. We conclude that the A(2B)R is subject to agonist
      induced desensitization with preserved expression of A(2B)R mRNA and protein.
      Uncoupling of the A2B adenosine receptor from the G protein complex may
      contribute to the mechanism of desensitization.

PMID- 9586959
TI  - Effects of 1-chloro-2,4,6-trinitrobenzene on 5-lipoxygenase activity and cellular
      leukotriene synthesis.
AB  - 5-Lipoxygenase (EC 1.13.11.34) is the key enzyme in the regulation of leukotriene
      synthesis. Here, the effects of various substituted nitrobenzene compounds on 5
      lipoxygenase activity and the formation of leukotriene B4 (LTB4) were studied in
      polymorphonuclear leukocytes (PMNL), B lymphocytes, and human whole blood. 1
      Chloro-2,4,6-trinitrobenzene (TNCB) was found to inhibit calcium ionophore A23187
      induced leukotriene synthesis in PMNL in a biphasic manner. Thus, 1.0 microM TNCB
      caused 50% inhibition of LTB4 formation, but only 16% inhibition was found at 10
      times higher concentration. In contrast, this higher concentration of TNCB
      activated the synthesis of LTB4 when PMNL were stimulated with arachidonic acid
      alone, demonstrating that TNCB can exert both stimulatory and inhibitory effects
      on leukotriene synthesis depending on the experimental conditions. The inhibitory
      effect of 1.0 microM TNCB on ionophore A23187-induced leukotriene synthesis could
      be circumvented by addition of exogenous arachidonic acid. At high concentrations
      of TNCB (25-100 microM), the drug blocked ionophore A23187-induced leukotriene
      synthesis. TNCB also inhibited LTB4 formation in B lymphocytes, as well as in
      human whole blood. The activity of recombinant 5-lipoxygenase was inhibited by
      TNCB, and reduced glutathione or beta-mercaptoethanol counteracted this
      inhibition. This suggests that TNCB might inhibit 5-lipoxygenase by alkylating
      thiol groups. TNCB possessed a high specificity for 5-lipoxygenase with only
      modest inhibitory effects on 12-lipoxygenase (EC 1.13.11.31), 15-lipoxygenase (EC
      1.13.11.12), and phospholipase A2 (EC 3.1.1.4) activities. Taken together, these
      results show that TNCB can both specifically inhibit and stimulate leukotriene
      formation and might be useful in further studies on the regulation of 5
      lipoxygenase.

PMID- 9586961
TI  - Different effects on [3H]noradrenaline uptake of the Aconitum alkaloids
      aconitine, 3-acetylaconitine, lappaconitine, and N-desacetyllappaconitine in rat
      hippocampus.
AB  - The effect of the Aconitum alkaloids aconitine, 3-acetylaconitine, lappaconitine,
      and N-desacetyllappaconitine to inhibit [3H]noradrenaline uptake was investigated
      in rat hippocampal synaptosomes. Aconitine and 3-acetylaconitine, which are known
      to activate sodium channels, had comparable inhibitory potencies and yielded Ki
      (inhibitor constant) values of 230 +/- 66 nM and 316 +/- 96 nM, respectively. In
      contrast, lappaconitine and N-desacetyllappaconitine failed to inhibit
      [3H]noradrenaline uptake. When either lappaconitine or N-desacetyllappaconitine
      was applied in combination with aconitine, [3H]noradrenaline uptake was not
      affected. The sodium channel blocker tetrodotoxin enhanced [3H]noradrenaline
      uptake, whereas uptake was completely blocked in sodium-free incubation medium.
      The inhibitory action of aconitine and 3-acetylaconitine on [3H]noradrenaline
      uptake was blocked by addition of tetrodotoxin. Patch clamp studies performed on
      cultured rat hippocampal neurons revealed an inhibitory action of lappaconitine
      and N-desacetyllappaconitine on whole cell sodium currents. It is concluded that
      the blockade of [3H]noradrenaline uptake evoked by aconitine and 3
      acetylaconitine is mediated indirectly by an increased sodium concentration in
      the synaptosomes.

PMID- 9586962
TI  - Role of cDNA-expressed human cytochromes P450 in the metabolism of diazepam.
AB  - The metabolic conversion of diazepam (DZ) to temazepam (TMZ, a C3-hydroxylation
      product of DZ) and N-desmethyldiazepam (NDZ, an N1-demethylation product of DZ)
      was studied using cDNA-expressed human cytochrome P450 (CYP) isozymes 1A2, 2B6,
      2C8, 2C9, 2C9R144C, 2E1, 3A4, and 3A5 and human liver microsomes from five organ
      donors. Of the CYPs examined, 3A5, 3A4, and 2B6 exhibited the highest enzymatic
      activities with turnovers ranging from 7.5 to 12.5 nmol of product
      formed/min/nmol for the total metabolism of DZ, while 2C8, 2C9, and 2C9R144C
      showed lesser and moderate activities. 1A2 and 2E1 produced insignificant amounts
      of metabolites of DZ. The regioselectivity of CYPs was determined, and 2B6 was
      found to catalyze exclusively and 2C8, 2C9, and 2C9R144C preferentially the N1
      demethylation of DZ to form NDZ. 3A4 and 3A5 catalyzed primarily the C3
      hydroxylation of DZ, which was more extensive than the N1-demethylation. The
      ratios of TMZ to NDZ formed in the metabolism of DZ by 3A4 and 3A5 were
      approximately 4:1. Enzyme kinetic studies indicated that 2B6- and 2C9-catalyzed
      DZ metabolism followed Michaelis-Menten kinetics, whereas 3A4 and 3A5 displayed
      atypical and non-linear curves in Lineweaver-Burk plots. Human liver microsomes
      converted DZ to both TMZ and NDZ at a ratio of 2:1. Our results suggest that
      hepatic CYP3A, 2C, and 2B6 enzymes have an important role in the metabolism of DZ
      by human liver.

PMID- 9586963
TI  - Stimulation of L-type Ca2+ current by the endothelin receptor A-selective
      antagonist, BQ-123 in ventricular cardiomyocytes isolated from the rabbit
      myocardium.
AB  - BQ-123 is extensively used as an antagonist at endothelin (ET) receptors, having
      selectivity at the ET(A) receptor subtype. In this study, the effects of BQ-123
      per se on action potentials, L-type calcium currents, and potassium currents,
      were examined in ventricular cardiomyocytes isolated from adult, male, New
      Zealand White rabbits, using the patch-clamp technique. BQ-123 (1 microM)
      increased (P < 0.02) the duration of the action potential to 267 +/- 36 ms from a
      control duration of 228 +/- 30 ms. BQ-123 did not have any effect on the inward
      rectifier or transient outward potassium currents, but increased (P < 0.02) the L
      type Ca2+ current to -2.76 +/- 0.3 nA from a control value of -2.45 +/- 0.28 nA.
      The increases in both duration of the action potential and L-type Ca2+ current
      were reversed upon washout (233 +/- 28 ms and -2.32 +/- 0.31 nA, respectively)
      and were not different from the control values in the absence of BQ-123. In
      contrast, the endothelin receptor antagonists, BQ-788, PD155080 and PD145065 (1
      10 microM) did not affect the L-type Ca2+ current. These results indicate that,
      unlike PD155080, BQ-788 and PD145065, the conventional ET(A) receptor-selective
      antagonist, BQ-123, exerts a unique positive effect on the L-type Ca2+ current in
      ventricular cardiomyocytes isolated from rabbit myocardium. The mechanism of
      action of BQ-123, therefore, is not confined to ET receptor antagonism.

PMID- 9586964
TI  - Effect of basic fibroblast growth factor on cholecystokinin-induced amylase
      release and intracellular calcium increase in male rat pancreatic acinar cells.
AB  - Isolated rat pancreatic acinar cells were used to investigate the effect of basic
      fibroblast growth factor (bFGF) on both amylase secretion and intracellular free
      calcium concentration ([Ca2+]i) in response to the calcium-mobilizing
      secretagogue cholecystokinin-octapeptide (CCK-8). Our data show that bFGF
      inhibited CCK-8-induced amylase release in a concentration-dependent manner and
      decreased the CCK-8-induced rise in [Ca2+]i. This inhibitory effect of bFGF on
      both amylase secretion and [Ca2+]i increase in response to CCK-8 was reverted
      when acinar cells were pretreated with 100 microM tyrphostin A25, a tyrosine
      kinase inhibitor. Tyrphostin A25 also inhibited Ca2+ influx induced by CCK-8.
      These results show that bFGF inhibits CCK-8-induced pancreatic response by a
      tyrosine kinase-dependent mechanism. A role for tyrosine phosphorylation in
      capacitative Ca2+ entry is suggested.

PMID- 9586965
TI  - Stimulation of biosynthetic activity by novel succinate esters in rat pancreatic
      islets.
AB  - Selected esters of succinic acid are currently under investigation as possible
      insulinotropic agents for the treatment of noninsulin-dependent diabetes
      mellitus. The aim of the present study was to investigate the effects of ten
      novel esters of succinic acid upon biosynthetic activity in rat pancreatic
      islets. In the absence of any other exogenous nutrient, glycerol-3-hydroxy-1,2
      dimethyl succinate (0.5 mM), D-arabitol-5-hydroxy-1,2,3,4-tetramethylsuccinate
      (0.5 mM), and 4-tert-butylsuccinate (2.5 mM) exerted little or no effect upon L
      [4-3H]phenylalanine incorporation into trichloroacetic acid-precipitable
      material. A modest but significant increase in biosynthetic activity to
      approximately 150% of basal value was found in the presence of L-threitol-1,2,4
      trimethylsuccinate (2.0 mM) and ethanediol-1,2-diethylsuccinate (2.5 mM). A two-
      to five-fold increase in protein biosynthesis was observed in islets exposed to
      propanediol-1,2-dimethylsuccinate, glycerol-1,2-dimethylsuccinate-3
      hydrogenosuccinate, L-threitol-3-succinoyl-1,2,4-trimethylsuccinate, glycerol-1,2
      dimethylsuccinate or ethanediol-1,2-dimethylsuccinate (2.5 mM each), these esters
      being mentioned in order of increasing biological efficiency. There was a
      significant correlation between these results and the insulinotropic action of
      the same esters. The present findings thus reinforce the view that such esters
      act as nutrients in islet cells and, therefore, offer the advantage over
      pharmacological agents currently used for the treatment of type-2 diabetes in
      stimulating both the biosynthetic and secretory activity of insulin-producing B
      cells.

PMID- 9586966
TI  - Stimulation of DNA synthesis in untransformed cells by the antiviral and
      antitumoral compound tricyclodecan-9-yl-xanthogenate (D609).
AB  - The antiviral and antitumor xanthate compound tricyclodecan-9-yl-xanthogenate
      (D609) is best known for its inhibitory effect on phosphatidylcholine-specific
      phospholipase C activity. Now we report that in NIH 3T3 cells, but not in several
      transformed cell types tested, D609 stimulated DNA synthesis when phosphocholine
      (PCho), insulin, or ATP was also present. Maximal co-mitogenic effects of D609
      were observed at 5 microg/mL, a concentration 4-6 times lower than that required
      to inhibit phospholipase C activity. The synergistic mitogenic effects of D609
      and PCho, but not of D609 and insulin, were associated with activation of p42
      and, to a lesser extent, p44 mitogen-activated protein (MAP) kinases. The results
      raise the possibility that the mitogenic activity of D609 in untransformed cells
      may contribute to its antiviral and antitumor effects.

PMID- 9586967
TI  - Arthroscopic treatment of malunited and nonunited avulsion fractures of the
      anterior tibial spine.
AB  - Ten patients, presenting with a 10 degrees to 25 degrees deficit of knee
      extension after an avulsion fracture of the anterior tibial spine, were
      arthroscopically treated with debridement and abrasion of the anterior spine.
      Notchplasty was also performed in five cases where there was a more severe
      deficit of extension. At follow-up (mean: 39.4 months) eight patients had
      recovered the full articular range of motion of the knee whereas two had a slight
      residual deficit of extension of between 3 degrees and 5 degrees. In no case was
      ligament stability compromised as compared with preoperative assessment.

PMID- 9586968
TI  - Quadrupled semitendinosus-gracilis autograft fixation in the femoral tunnel: a
      comparison between a metal and a bioabsorbable interference screw.
AB  - Although semitendinosus-gracilis (SG) grafts for anterior cruciate ligament
      reconstruction have many potential benefits, effective fixation remains a
      challenge. This study assessed differences between the maximum pullout forces
      needed to detach a quadrupled SG graft from a femoral tunnel when secured by
      either a metal or a bioabsorbable interference screw. Sixteen paired fresh frozen
      quadrupled SG autografts (x, 8.4 mm; range, 7-10 mm) from 8 donors were anchored
      into cadaveric femoral tunnels by either a 7-mm metal or a 7-mm bioabsorbable
      screw after bone mineral density (BMD) assessment and before undergoing a
      longitudinal 20 mm/min traction force. Statistical analysis compared BMD
      (gm/cm2), insertional torque (N-m), and maximum load at pullout (N) between screw
      types. Insertional torques (.28-1.21, N-m range) did not correlate (P>.05) to BMD
      or maximum load at pullout (x +/- S.D.) 242 +/- 90.7 N (metal screw) and 341.1 +/
      162.9 N (bioabsorbable screw). Differences did not exist between the maximum
      load at pullout for bioabsorbable or metal screw fixation (P = .16). Careful
      graft preparation, sizing, and matched tunnel placement enables interference fit
      and fixation capable of reliably withstanding the low-level rehabilitation loads
      to which the graft is exposed until bony ingrowth occurs.

PMID- 9586969
TI  - Dislocating anterior horn of the medial meniscus.
AB  - Dislocating anterior horn of the medial meniscus was found in 15 knees of 13
      patients during arthroscopic examinations done between 1992 and 1995. All of them
      were available for follow-up evaluation (4 by telephone). There were 11 men and 2
      women (average age, 28 years; range, 17 to 49 years). Nine knees had a history of
      trauma. Only 1 knee had had trauma in two bilateral cases. Duration of symptoms
      was an average of 3.3 years (range, 3 months to 10 years). The knees were stable
      clinically. Arthroscopy revealed associated lesions in 13 knees; hypertrophic
      medial plicae, meniscal, chondral and anterior cruciate ligament (ACL) lesions
      predominated. Three knees had unusually hypertrophic ligamentum mucosum. Eleven
      of 13 knees had more than one associated lesions. Only 2 knees (2 patients) had
      isolated dislocating anterior horn of the medial meniscus. Only the associated
      lesions were treated (except for ACL lesions) and dislocating anterior horns of
      the medial menisci were left alone. Follow-up averaged 21 months (7 to 40
      months). At follow-up, 11 knees were graded as excellent, 3 as good, and 1 as
      fair according to the Lysholm scale. Eight knees had minor symptoms and 6 were
      asymptomatic; no improvement was noted in 1 knee. Overall, 12 patients (14 knees)
      were satisfied with their treatment. Dislocating anterior horn of the medial
      meniscus is a normal anatomic variant with little or no clinical significance.
      When seen during arthroscopy, a significant lesion should be looked for. It is an
      incidental finding and should be left alone.

PMID- 9586970
TI  - Architectural remodeling in deep frozen meniscal allografts after total
      meniscectomy.
AB  - This study assesses the biological characteristics of cell repopulation and
      matrix remodeling in deep frozen meniscal allografts after total meniscectomy and
      allograft transplantation. Thirty-two mature New Zealand White rabbits were
      operated on, and the allografts were assessed at 12 and 26 weeks postsurgery.
      Before transplantation, fresh medial menisci were placed into liquid nitrogen to
      kill all intrinsic cells. Frozen meniscal allografts showed collagen remodeling
      coincident with revascularization and cellular repopulation. Biochemical
      characterization showed active collagen remodeling of the allografts at 12 and 26
      weeks. In situ hybridization showed that expression of types I and III
      procollagen mRNAs were increased at 12 weeks, especially near the region of the
      synovial capsule. At 26 weeks after transplantation, the pattern of collagen-type
      expression progressed toward normal; that is, type I procollagen mRNA expression
      was prominent, whereas only a small amount of type III procollagen mRNA was
      observed. These data indicate the adaptation of the repopulating cells from the
      host to the frozen allograft at 26 weeks after transplantation.

PMID- 9586971
TI  - Cross-pin femoral fixation: a new technique for hamstring anterior cruciate
      ligament reconstruction of the knee.
AB  - A new method of femoral fixation for arthroscopic anterior cruciate ligament
      (ACL) reconstruction using semitendinosus and gracilis (ST/G) tendons is
      presented. Biomechanical evaluation of the method was performed with pullout
      tests using animal tissues simulating fixation of ST/G tendons passing around a
      2.5-mm pin placed transversely through a femoral tunnel. Clinical assessment of
      22 patients was performed according to IKDC, Tegner, Lysholm, isokinetic
      strength, and KT1000 standards. Fixation strengths ranged from 725 N to 1,600 N
      for yield and maximal loads to failure for 35-mm to 70-mm cross-pins. Clinical
      results at mean follow-up of 30 months showed one traumatic failure, IKDC 86%
      normal or nearly normal, Tegner 6 ave, Lysholm 93 ave, KT1000 86% < 3 mm side-to
      side difference on maximal manual evaluation, and isokinetic strength testing of
      quadriceps 8% deficit with hamstrings 8% deficit. Cross-pin fixation of ST/G
      tendons may be one of the strongest modes of femoral graft attachment yet
      devised. Our clinical outcomes in this initial series compare well with previous
      reports of ACL reconstruction regardless of graft or technique.

PMID- 9586972
TI  - Arthroscopic-assisted outpatient anterior cruciate ligament reconstruction using
      the semitendinosus and gracilis tendons.
AB  - This study presents an average of 43-month results (range, 23 to 75 months) of 82
      arthroscopically assisted, outpatient semitendinosus-gracilis anterior cruciate
      ligament reconstructions evaluated with the Cincinnati Knee Rating System. There
      were 44 acute and 38 chronic injuries. The results showed no significant effect
      of injury chronicity on all outcome variables except knee motion complications.
      Additionally, no significant difference was found between men and women in
      regards to outcome. At follow-up, 93% showed complete or partial graft function,
      98% had a full range of knee motion, 83% had returned to sports with no problems,
      and 92% rated their knee condition as normal or very good. The mean overall point
      score (0 to 100 scale) for all patients was 92 +/- 10 points. All patients with
      chronic injuries showed improvement from their preoperative status, including 11
      who had articular cartilage lesions. Complications were few; only five patients
      (6%) needed additional treatment for limitation of knee motion, and no patient
      had an increase in patellofemoral crepitus. We concluded that this procedure
      produced desirable results and that patients with long-standing functional
      limitations significantly improved and were able to return to an active
      lifestyle.

PMID- 9586973
TI  - Initial fixation strength of polylactic acid interference screws in anterior
      cruciate ligament reconstruction.
AB  - The initial fixation properties of bioresorbable polylactic acid (PLA)
      interference screws designed for anterior cruciate ligament reconstruction were
      evaluated using an in vitro bovine model. The surgical technique of interference
      screw fixation of the bone-patellar tendon-bone autograft complex performed
      clinically was reproduced in an adult bovine model. The reconstructed knee was
      tested oriented in 30 degrees of flexion to allow examination of the femoral and
      tibial fixation properties simultaneously. This model examined the initial
      fixation strength between PLA and metal interference screws as well as a
      partially degraded PLA implant. Data from this in vitro model indicate that PLA
      interference screws can provide similar initial fixation at both time 0 and after
      degradation for up to 28 days compared with metal interference screws for bone
      tendon-bone ACL reconstructions.

PMID- 9586974
TI  - Posterior to anterior transglenoid pins: anatomy at risk.
AB  - Pneumothorax was noted after an arthroscopic procedure during which a small
      guidewire overpenetrated the glenoid from a posterior-superior direction. This
      anatomic study was undertaken to determine the structures at risk from pins
      overpenetrating from the posterior-superior aspect and to determine whether
      scapulothoracic position altered the risk. The glenoid was intentionally
      overpenetrated with wooden dowels from the posterior-superior aspect of the
      glenoid in seven fresh cadaveric shoulders. The dowels were placed
      arthroscopically using the Suretac instrumentation (Acufex Microsurgical,
      Mansfield, MA). The specimens were planed, and the relationship of these wooden
      pins to vital structures was evaluated. In all specimens, the dowels entered the
      thoracic cavity between the first and second ribs, regardless of scapular
      position. The pins consistently passed posterior to the neurovascular bundle but
      were precariously close, with an average distance to the closest neurovascular
      structure of 7.4 mm (range, 1 to 19 mm). Scapular position did not seem to affect
      this relationship.

PMID- 9586975
TI  - Primary traumatic anterior shoulder dislocation in patients 40 years of age and
      older.
AB  - During three consecutive ski seasons (1991 to 1994), 125 patients 40 years of age
      and older without previous shoulder injuries or surgery sustained a traumatic
      first-time anterior shoulder dislocation. At a minimum of 2 years' follow-up,
      patients were contacted to determine long-term outcome and to identify factors
      leading to prolonged morbidity or the need for surgical intervention. Fifty-two
      patients were available for interview. A modified Rowe shoulder score showed 32
      excellent, nine good, eight fair, and three poor results. Eighteen (35%) rotator
      cuff tears were subsequently identified, with only 11 (61%) of these patients
      obtaining an excellent or good outcome (P = .011). Of the 11 patients with a fair
      or poor result, seven (64%) had a rotator cuff tear. Of the 12 patients with
      isolated cuff tears, 84% had an excellent or good result when treated surgically,
      compared with 50% when treated nonsurgically. Our findings indicate that
      recurrence is not a frequent complication of traumatic anterior shoulder
      dislocation in this age-group (4%). However, prolonged morbidity secondary to
      rotator cuff tear is more prevalent than in a younger population. We believe
      early diagnosis of rotator cuff pathology by either magnetic resonance imaging
      (MRI) or arthrogram with subsequent surgical repair can lead to faster
      restoration of function and a better outcome in these select individuals.

PMID- 9586976
TI  - Arthroscopic Bankart suture repair for traumatic anterior shoulder instability:
      analysis of the causes of a recurrence.
AB  - Eighty-two patients with traumatic anterior shoulder instability were treated
      with an arthroscopic transglenoid multiple suture technique (Caspari's method)
      and followed-up for more than 2 years. A retrospective analysis of the clinical
      outcome was performed to determine the factors related to poor results. The mean
      age at operation was 21 years (range, 13 to 50 years) and the mean follow-up
      period was 40 months (range, 24 to 70 months). According to the status of the
      ligament-labrum complex and the glenoid bone defect, the Bankart lesions were
      classified into five types arthroscopically. There were 21 shoulders of type 1,
      33 shoulders of type 2, 22 shoulders of type 3, and 6 shoulders of type 5. Twenty
      four of the patients played contact sports before the operation. The clinical
      outcome was assessed by Rowe's criteria (1978). To analyze the factors related to
      a poor outcome, a multivariate analysis was done to assess the influence of 12
      clinical factors (age at operation, age at first dislocation, sex, dominant side,
      disease duration, number of dislocations, sporting activity before operation,
      inferior joint laxity, thickness of the ligament-labrum complex, type of Bankart
      lesion, number of sutures, and method of suture fixation). Fifty-five of 82
      patients had an excellent outcome, 14 had a good result, and 13 had a poor
      result. According to postoperative instability, redislocation was seen in 13
      patients (16%), resubluxation in 2 patients (2%), with a recurrence rate of 18%.
      The mean limitation of external rotation at 90 degrees abduction was 6.0 degrees
      (range, 0 degrees to 30 degrees), and there was a 10 degrees loss of external
      rotation in 10 patients. The factors significantly related to recurrence were a
      type 3 Bankart lesion, playing contact sports preoperatively, a thin ligament
      labrum complex, and repair with less than four sutures. In conclusion, a 18% rate
      of recurrence is not acceptable. To obtain a better clinical outcome, very
      careful selection of patients for this technique is necessary. Our analysis of
      the factors related to a poor outcome may help to decide what the proper
      indications are for this technique.

PMID- 9586977
TI  - Humeral attachment of the supraspinatus and infraspinatus tendons: an anatomic
      study.
AB  - We investigated the anatomic relationship of the supraspinatus (SSP) and
      infraspinatus (ISP) tendons to the three facets of the greater tuberosity. After
      removing the superficial layer of the cuff to expose the tendon fibers in 10
      embalmed shoulders, the cuff tendon attachment to the facets was examined, and
      the location of attachment was measured in reference to (1) the anterior margin
      of the greater tuberosity and (2) the superior margin of the sulcus (anatomic
      neck without cartilage). The SSP tendon attached to the superior facet and the
      superior half of the middle facet. The ISP tendon attached to the entire middle
      facet, covering a portion of the SSP tendon. Thus, the anterior half of the
      superior cuff tendon (12.6 +/- 1.1 mm) was composed of only the SSP tendon,
      whereas the posterior half (9.8 +/- 3.2 mm) was composed of both the SSP and ISP
      tendons. The sulcus was located not at the SSP-ISP interval but slightly
      posterior to the posterior margin of the SSP tendon (4.3 +/- 2.4 mm). We conclude
      that (1) there is an overlap between the SSP and ISP tendons identifiable by the
      facets or the distance from the anterior greater tuberosity and (2) the sulcus is
      located slightly posterior to the posterior margin of the SSP tendon.

PMID- 9586978
TI  - Arthroscopic cheilectomy for hallux rigidus.
AB  - Hallux rigidus is a disabling problem especially in younger patients. Open
      cheilectomy or exostosectomy for treatment has been reported with satisfactory
      results. Analysis of a series of 15 patients who underwent arthroscopic
      cheilectomy for hallux rigidus has shown very satisfactory and encouraging early
      results without any recurrence or any need of revision surgery. This has provided
      rapid recovery and rehabilitation as well as maintained the pain relief with good
      metatarso-phalangeal joint power and motion.

PMID- 9586979
TI  - Cancellous bone grafting of large osteochondral defects: an experimental study in
      dogs.
AB  - Autogenous cancellous bone was evaluated as a material to repair large
      osteochondral defects in 20 adult mongrel dogs. In one knee, the bone graft was
      used to fill an osteochondral cylindrical defect (10 mm diameter x 10 mm deep)
      created in the femoral trochlea. A similar lesion was created in the
      contralateral knee but was left untreated for spontaneous healing. Four animals
      were killed at each of five periods (2, 4, 8, 12, and 24 weeks), and the healing
      response of the defects was evaluated by gross anatomic inspection, plain film
      radiography, high-resolution radiography, and histology. The results of this
      study suggest that the use of a cancellous bone graft accelerates the repair of
      large osteochondral defects and produces more uniform filling of the defect than
      the ungrafted control. The reparative surface of the grafted lesions also
      differed from that of controls, having uniform coverage with histochemical
      positive staining fibrocartilage at 8 weeks, a finding not observed in any
      control defect through the length of this study, 24 weeks.

PMID- 9586980
TI  - Knee joint arthroscopy in the morbidly obese.
AB  - Ten morbidly obese individuals were retrospectively reviewed to determine the
      technical problems and incidence of surgical complications associated with knee
      joint arthroscopy in this subpopulation of patients. In comparison to a cohort of
      patients of normal weight that were matched for age, sex, and surgical procedure,
      the morbidly obese patients had longer operative times (P < .02) and time to work
      resumption despite having less physically demanding jobs. Those with morbid
      obesity required a greater number of arthroscopy portals to effect a thorough
      arthroscopic examination (P < .02). Many technical problems involved the fact
      that these patients' size could not be accommodated by standard equipment. There
      were no wound or neurovascular complications and one presumed thromboembolic
      event.

PMID- 9586981
TI  - Glomus tumor of the fat pad.
AB  - The authors report an exceptional glomus tumor location in Hoffa's ligament in a
      65-year-old man. Based on this observation and a literature review, the authors
      provide the clinical and radiographic diagnostic appearances of this type of
      tumor. Surgical removal of the tumor achieved immediate disappearance of knee
      pain. Histological examination of the tumor has established the definitive
      diagnosis.

PMID- 9586982
TI  - Foreign body gonitis caused by a broken poly-L-lactic acid screw.
AB  - Poly-L-lactic acid (PLLA), a biodegradable polymer, is generally considered to be
      gradually degraded without causing any severe tissue reaction. However, we
      encountered a patient who developed foreign body gonitis caused by screw breakage
      after fixation of an intercondylar prominence fracture with PLLA screws. This
      case suggests that care should be taken when PLLA materials are used to fix
      intraarticular fractures.

PMID- 9586983
TI  - Epidermoid cyst after arthroscopic knee surgery.
AB  - Eleven years after an arthroscopic procedure, a benign tumor of the knee located
      beneath the scar where the outflow canula was placed was excised.
      Histomorphological evaluation determined the diagnosis of an epidermoid cyst.
      This is the first case reported in the literature of an epidermoid cyst occurring
      after an arthroscopic operation. The previous epidermoid cysts reported were
      found after trauma or after dermal grafting for epithelium implantation.

PMID- 9586984
TI  - Anterior cruciate ligament deficiency accompanied by patellar subluxation treated
      by reconstruction with lateral retinacular release.
AB  - Five patients with an anterior cruciate ligament (ACL) deficiency accompanied by
      patellar subluxation who were treated by ACL reconstruction with lateral
      retinacular release (LRR) are reported. In two patients, the LRR was performed at
      the same time as the ACL reconstruction, and in three patients, the LRR was
      performed secondarily. The three patients requiring the secondary LRR needed the
      procedure to recover knee stability to return to sporting activities. In all
      patients, the apprehension sign of the patella was subsequently improved. When
      managing ACL deficiencies in a young athletic population, patellar subluxation
      should be suspected. In our patients with patellar subluxation accompanying an
      ACL deficiency, ACL reconstruction with LRR was effective in relieving their
      instability.

PMID- 9586986
TI  - Fold me deadly.

PMID- 9586985
TI  - Achilles allograft reconstruction of a chronic patellar tendon rupture.
AB  - Chronic ruptures of the patellar tendon are uncommon injuries. They are
      technically difficult to repair because of scar formation, poor quality of the
      remaining tendon, and quadriceps muscle atrophy and contracture. We report the
      reconstruction of a chronic patellar tendon rupture with an interesting
      complication, a tibial stress fracture. The reconstruction was performed 3 months
      after the injury using an Achilles tendon-bone allograft and reinforcing
      suprapatellar wire. At 2 weeks postoperatively, the patient had attained full
      extension and 90 degrees of flexion. Ten months after the index procedure, the
      patient had range of motion 0 degrees to 120 degrees and was diagnosed with a
      healing tibial stress fracture. At 17 months postoperatively, the patient had
      attained full extension, 120 degrees of flexion, and 85% quadriceps strength. The
      preoperative goals of attaining full range of motion, improving quadriceps
      strength, obtaining anatomic patellar alignment, and restoring function were
      obtained despite the complication of a tibial stress fracture. Although this
      reconstructive procedure is technically demanding, with potential complications,
      the functional results obtained can be excellent.

PMID- 9586987
TI  - RNA-mediated signaling in transcription.
AB  - Structures of phage transcriptional antitermination complexes define novel motifs
      for recognition of RNA hairpins by arginine-rich peptides. A bent alpha-helix in
      each case follows the contour of an induced GNRA-like fold. A phage-specific
      pattern of base pairing, base stacking and base flipping underlies biological
      specificity and permits engagement with RNA polymerase. The structures suggest a
      mechanism of RNA-mediated signaling in transcriptional regulation.

PMID- 9586988
TI  - The thermosome: chaperonin with a built-in lid.

PMID- 9586989
TI  - The parallel universe of RNA folding.
AB  - How do large RNA molecules find their active conformations among a universe of
      possible structures? Two recent studies reveal that RNA folding is a rapid and
      ordered process, with surprising similarities to protein folding mechanisms.

PMID- 9586990
TI  - Ligand-free MHC class I conformation.
AB  - Perhaps the most important structural questions regarding MHC molecules concern
      what changes occur when the MHC molecule binds peptide. Extensive new biochemical
      evidence indicates that peptide-empty MHC class I molecules adapt an unstable and
      partially folded conformation.

PMID- 9586991
TI  - At last, the structure of an ion-selective channel.
AB  - Ion channels allow specific ions to flow across the cell membrane at rates of ten
      million ions per second with error rates of only 1 in 1,000. The structure of a
      protein that accomplishes this feat has now been discovered.

PMID- 9586992
TI  - Picture story. To kill or not to kill.

PMID- 9586993
TI  - History in the making.

PMID- 9586994
TI  - Novel non-heme iron center of nitrile hydratase with a claw setting of oxygen
      atoms.
AB  - The iron-containing nitrile hydratase (NHase) is a photoreactive enzyme that is
      inactivated in the dark because of persistent association with NO and activated
      by photo-dissociation of NO. The crystal structure at 1.7 A resolution and mass
      spectrometry revealed the structure of the non-heme iron catalytic center in the
      nitrosylated state. Two Cys residues coordinated to the iron were post
      translationally modified to Cys-sulfenic and -sulfinic acids. Together with
      another oxygen atom of the Ser ligand, these modifications induced a claw setting
      of oxygen atoms capturing an NO molecule. This unprecedented structure is likely
      to enable the photo-regulation of NHase and will provide an excellent model for
      designing photo-controllable chelate complexes and, ultimately, proteins.

PMID- 9586995
TI  - Crystal structure of the RNA-binding domain from transcription termination factor
      rho.
AB  - Transcription termination factor rho is an ATP-dependent hexameric helicase found
      in most eubacterial species. The Escherichia coli rho monomer consists of two
      domains, an RNA-binding domain (residues 1-130) and an ATPase domain (residues
      131-419). The ATPase domain is homologous to the beta subunit of F1-ATPase. Here,
      we report that the crystal structure of the RNA-binding domain of rho (rho130) at
      1.55 A confirms that rho130 contains the oligosaccharide/oligonucleotide-binding
      (OB) fold, a five stranded beta-barrel. The beta-barrel of rho130 is also
      surprisingly similar to the N-terminal beta-barrel of F1 ATPase, extending the
      applicability of F1 ATPase as a structural model for hexameric rho.

PMID- 9586996
TI  - Crystal structure and reaction mechanism of 7,8-dihydroneopterin aldolase from
      Staphylococcus aureus.
AB  - Dihydroneopterin aldolase catalyzes the conversion of 7,8-dihydroneopterin to 6
      hydroxymethyl-7,8-dihydropterin during the de novo synthesis of folic acid from
      guanosine triphosphate. The gene encoding the dihydroneopterin aldolase from S.
      aureus has been cloned, sequenced and expressed in Escherichia coli. The protein
      has been purified for biochemical characterization and its X-ray structure
      determined at 1.65 A resolution. The protein forms an octamer of 110,000 Mr
      molecular weight. Four molecules assemble into a ring, and two rings come
      together to give a cylinder with a hole of at least 13 A diameter. The structure
      of the binary complex with the product 6-hydroxymethyl-7,8-dihydropterin has
      defined the location of the active site. The structural information and results
      of site directed mutagenesis allow an enzyme reaction mechanism to be proposed.

PMID- 9586997
TI  - The core of apomyoglobin E-form folds at the diffusion limit.
AB  - The E-form of apomyoglobin has been characterized using infrared and fluorescence
      spectroscopies, revealing a compact core with native like contacts, most probably
      consisting of 15-20 residues of the A, G and H helices of apomyoglobin. Fast
      temperature-jump, time-resolved infrared measurements reveal that the core is
      formed within 96 micros at 46 degrees C, close to the diffusion limit for loop
      formation. Remarkably, the folding pathway of the E-form is such that the
      formation of a limited number of native-like contacts is not rate limiting, or
      that the contacts form on the same time scale expected for diffusion controlled
      loop formation.

PMID- 9586998
TI  - An engineered ribonuclease preferring phosphorothioate RNA.
AB  - We used mutants of RNase T1 and the Rp isomer of a thiosubstituted substrate to
      determine stereospecific thioeffects on catalysis. The analysis reveals subtle
      structural and functional changes in the intermolecular transition state
      interactions. Tyr 38 contributes to catalysis through a hydrogen bond with the
      pro-Rp oxygen. Y38F RNase T1 prefers the Rp thiosubstituted analog over the
      natural phosphodiester substrate that is favored by the wild type enzyme.

PMID- 9586999
TI  - Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using
      data at a single wavelength.
AB  - S-Adenosylhomocysteine (AdoHcy) hydrolase regulates all adenosylmethionine
      (AdoMet) dependent transmethylations by hydrolyzing the potent feedback inhibitor
      AdoHcy to homocysteine and adenosine. The crystallographic structure
      determination of a selenomethionyl-incorporated AdoHcy hydrolase inhibitor
      complex was accomplished using single wavelength anomalous diffraction data and
      the direct methods program, Snb v2.0, which produced the positions of all 30
      crystallographically distinct selenium atoms. The mode of enzyme-cofactor binding
      is unique, requiring interactions from two protein monomers. An unusual dual role
      for a catalytic water molecule in the active site is revealed in the complex with
      the adenosine analog 2'-hydroxy, 3'-ketocyclopent-4'-enyladenine.

PMID- 9587000
TI  - Structural characterization of a soluble and partially folded class I major
      histocompatibility heavy chain/beta 2m heterodimer.
AB  - Class I major histocompatibility (MHC) heavy chain (HC) must fold and assemble
      with beta 2 microglobulin (beta 2m) prior to binding peptides in the endoplasmic
      reticulum (ER). Each of these events is mediated by association with chaperones
      and other proteins and is an essential requirement for the maturation and normal
      cell surface expression of stable class I MHC-peptide complexes. Here we describe
      the biochemical and structural characterization of a soluble HC (B*0702)/beta 2m
      heterodimer, apparently free of peptide. Results suggest that the peptide binding
      domains (alpha 1 and alpha 2) of this folding intermediate are unstable and
      possess many of the properties ascribed to the molten globule state. The
      partially folded state of the HC/beta 2m heterodimer is consistent with the
      suggestion that it is stabilized by chaperones and other proteins in the ER. This
      soluble intermediate may be useful for studying protein-assisted folding and
      peptide binding of class I MHC molecules.

PMID- 9587001
TI  - Evidence for barrier-limited protein folding kinetics on the microsecond time
      scale.
AB  - Although important structural events in protein folding are known to occur on the
      submillisecond time scale, the limited time resolution of conventional kinetic
      methods has precluded direct observation of the initial collapse of the
      polypeptide chain. A continuous-flow capillary mixing method recently developed
      by us made it possible to account for the entire fluorescence change associated
      with refolding of cytochrome c from approximately 5-10(-5)-10(2) s, including the
      previously unresolved quenching of Trp 59 fluorescence (burst phase) indicative
      of the formation of compact states. The kinetics of folding exhibits a major
      exponential process with a time constant of approximately 50 micros, independent
      of initial conditions and heme ligation state, indicating that a common free
      energy barrier is encountered during the initial collapse of the polypeptide
      chain. The resulting loosely packed intermediate accumulates prior to the rate
      limiting formation of specific tertiary interactions, confirming previous
      indications that folding involves at least two distinct stages.

PMID- 9587002
TI  - The NMR structure of the RNA binding domain of E. coli rho factor suggests
      possible RNA-protein interactions.
AB  - Rho protein is an essential hexameric RNA-DNA helicase that binds nascent mRNA
      transcripts and terminates transcription in a wide variety of eubacterial
      species. The NMR solution structure of the RNA binding domain of rho, rho130, is
      presented. This structure consists of two sub-domains, an N-terminal three-helix
      bundle and a C-terminal beta-barrel that is structurally similar to the
      oligosaccharide/oligonucleotide binding (OB) fold. Chemical shift changes of
      rho130 upon RNA binding and previous mutagenetic analyses of intact rho suggest
      that residues Asp 60, Phe 62, Phe 64, and Arg 66 are critical for binding and
      support the hypothesis that ssRNA/ssDNA binding is localized in the beta-barrel
      sub-domain. On the basis of these studies and the tertiary structure of rho130,
      we propose that residues Asp 60, Phe 62, Phe 64, Arg 66, Tyr 80, Lys 105, and Arg
      109 participate in RNA-protein interactions.

PMID- 9587003
TI  - Crystal structure of a novel human peroxidase enzyme at 2.0 A resolution.
AB  - Hydrogen peroxide (H2O2) has been implicated recently as an intracellular
      messenger that affects cellular processes including protein phosphorylation,
      transcription and apoptosis. A set of novel peroxidases, named peroxiredoxins
      (Prx), regulate the intracellular concentration of H2O2 by reducing it in the
      presence of an appropriate electron donor. The crystal structure of a human Prx
      enzyme, hORF6, reveals that the protein contains two discrete domains and forms a
      dimer. The N-terminal domain has a thioredoxin fold and the C-terminal domain is
      used for dimerization. The active site cysteine (Cys 47), which exists as
      cysteine-sulfenic acid in the crystal, is located at the bottom of a relatively
      narrow pocket. The positively charged environment surrounding Cys 47 accounts for
      the peroxidase activity of the enzyme, which contains no redox cofactors.

PMID- 9587004
TI  - Adverse effects associated with contraceptive implants: incidence, prevention and
      management.
AB  - Contraceptive implants are increasingly being used for fertility regulation all
      over the world. Reversible long-term use is their most appealing feature for many
      users. They have the practical advantage of overcoming the risks of user failure
      and low continuation rates associated with other methods that require continuous
      attention or motivation. Disruption of menstruation, complications of insertion
      and removal, and infection at implant site, constitute the majority of adverse
      effects associated with contraceptive implants. This article reviews these
      various common adverse effects associated with contraceptive implants and their
      possible management and prevention. In addition, we also discuss very rare
      events, like psychiatric disorders, pseudotumor cerebri, thrombotic,
      thrombocytopenic purpura and thrombocytopenia, that have been reported by some
      researchers. Further surveillance and research is necessary to determine if these
      rare adverse events are causally related to contraceptive implants. Until such a
      time, providers of contraceptive implants should be more selective in prescribing
      the contraceptive implants, especially in women with a history of and/or risk
      factors for stroke, cerebral and coronary heart disease, thrombocytopenia and
      pseudotumor cerebri.

PMID- 9587005
TI  - Contraceptive efficacy and acceptability of a monophasic oral contraceptive
      containing 30 microg ethinyl estradiol and 150 microg desogestrel in Latin
      American women.
AB  - Contraceptive efficacy, subject acceptability (cycle control, side-effects, acne
      score and weight gain) and blood pressure of a monophasic oral contraceptive
      containing 30 microg ethinyl estradiol plus 150 microg desogestrel (Marvelon)
      were assessed in an open-label 6-cycle multicenter study in Argentina (7 centers)
      and Venezuela (5 centers). Of the 407 participating women, 389 (95.6%) completed
      six cycles of treatment, providing data for a total of 2383 cycles. No
      pregnancies occurred during the course of the study, confirming the high
      contraceptive reliability of Marvelon. Cycle control was excellent; the duration
      of withdrawal bleeding decreased during consecutive treatment cycles and the
      incidence of spotting and breakthrough bleeding was low. The desogestrel/ethinyl
      estradiol combination was well tolerated and the incidence of minor side-effects,
      which was already low in the first treatment cycle, in most cases decreased
      during the subsequent cycles. The preparation was effective in reducing pre
      existing acne, whereas it did not induce clinically relevant changes in blood
      pressure and body weight. Marvelon was shown to provide effective oral
      contraception, with good tolerance and excellent cycle control in Latin-American
      women.

PMID- 9587006
TI  - Provider attitudes toward IUD provision in Zimbabwe: perception of HIV risk and
      training implications.
AB  - This study was conducted to assess providers' attitudes toward the provision of
      long-term methods of contraception, in particular the IUD, and provider concerns
      about human immunodeficiency virus (HIV) in the context of family planning (FP)
      services. The data were collected using self-administered structured
      questionnaires. Between 65% and 80% of the public and private providers thought
      that the IUD is a good contraceptive method for Zimbabwean women. In addition,
      the majority of these two provider groups felt that neither the IUD nor tubal
      sterilization (TL) posed much risk of HIV infection to the client. A significant
      number of providers (especially the public nurses), however, thought that the
      provision of TL put the provider at high risk of HIV infection and a significant
      proportion of public nurses were also concerned about provider risk associated
      with providing IUD and injectables. To address such concerns, future training
      interventions should emphasize appropriate infection prevention practices
      associated with surgical FP method provision. Nurses, in particular, should be
      informed about the magnitude of risk associated with FP service provision and
      ways to protect themselves. Logistic activities also need to be strengthened so
      that legitimate concerns among providers regarding lack of adequate infection
      prevention supplies (e.g. gloves) in the field can be addressed.

PMID- 9587007
TI  - New directions in IUCD development.
AB  - In recent years, the development of improved intrauterine devices has focused on
      finding methods to reduce expulsion and the need for medical removal for better
      intrauterine retention and devices. Efforts also have been directed towards
      developing intracervical devices. Some of the more recent developments in
      intrauterine and intracervical devices are discussed.

PMID- 9587008
TI  - Non-physician insertion of IUDs: clinical outcomes among TCu380A insertions in
      three developing-country clinics.
AB  - Insertion of IUDs by trained non-physicians is increasing. This secondary
      analysis of TCu380A IUD acceptors collected at clinics in Nigeria, Turkey and
      Mexico involved 367 women; 193 insertions were performed by physicians and 174 by
      non-physicians. Women having their IUD inserted by a non-physician were more
      likely to experience a pain-free insertion, but also likelier to have the IUD
      removed for bleeding and pain or to experience an expulsion than women who had
      their IUD inserted by a physician. Early discontinuation rates were similar
      between the two groups. Overall continuation rates were statistically higher for
      IUDs inserted by physicians only at the Mexico site. Trained non-physicians can
      probably safely insert the TCu380A IUD. Appropriate competency-based training is
      required to limit the number of expulsions and removals for bleeding and pain by
      non-physicians.

PMID- 9587009
TI  - Contraceptive use and pregnancy before and after introducing lactational
      amenorrhea (LAM) in a postpartum program.
AB  - There is good evidence that lactational amenorrhea (LAM) is an effective method
      of fertility regulation during the first 6 months postpartum, provided no other
      food is given to the baby and the mother remains amenorrheic. However, although
      breast-feeding is strongly promoted in many maternity hospitals that also run
      postpartum family planning programs, LAM is rarely included among the
      contraceptive options being offered. This paper presents the results of an
      operational study which compared the prevalence of contraceptive use and the
      cumulative pregnancy rate at 12-months postpartum among 350 women observed before
      and 348 women studied after introducing LAM as an alternative contraceptive
      option offered to women following delivery at the Instituto Materno Infantil de
      Pernambuco (IMIP), in Recife, Brazil. The percentage of women not using any
      contraceptive method was significantly lower (p<0.0001) after the intervention
      (7.4%) than before (17.7%). This difference remained statistically significant
      after controlling for age, number of living children, marital status and years of
      schooling. The proportion pregnant one year postpartum was also significantly
      lower (p<0.0001) after the introduction of LAM (7.4%) than before (14.3%), but
      the difference was no longer significant after controlling for the same
      variables. It is concluded that LAM is a useful addition to family planning
      postpartum programs.

PMID- 9587010
TI  - Four-year clinical evaluation of quinacrine pellets for non-surgical female
      sterilization.
AB  - The aim of this study was to evaluate the efficacy, safety and acceptability of
      two monthly transcervical applications of quinacrine 252 mg and ibuprofen 55.5 mg
      as pellets for non-surgical female sterilization. From August 1992 through
      October 1996, a prospective clinical study was conducted on 200 normal women
      seeking surgical sterilization voluntarily in the Family Planning Clinic of the
      Department of Obstetrics and Gynecology, Regency Hospital, Wonosobo, Central
      Java, Indonesia. Quinacrine 252 mg and ibuprofen 55.5 mg were inserted
      transcervically, as pellets, using a Copper T IUD insertor in the proliferative
      phase of two consecutive menstrual cycles. The women were followed up 6, 12, 24
      and 48 months after insertion. There were no major complications during the
      insertion procedures, and side-effects which occurred during the use of the
      methods were transient. Cumulative life-table continuation rate per 100 women at
      four years was 0.91+/-0.02 (SE). The pregnancy failure rate was 0.04 or 4.3%. The
      results of this study indicate that intrauterine insertion of quinacrine pellets
      is a safe, acceptable and effective method of non-surgical female sterilization.

PMID- 9587011
TI  - Induction by mercury compounds of brain metallothionein in rats: Hg0 exposure
      induces long-lived brain metallothionein.
AB  - Metallothionein (MT) is one of the stress proteins which can easily be induced by
      various kind of heavy metals. However, MT in the brain is difficult to induce
      because of blood-brain barrier impermeability to most heavy metals. In this
      paper, we have attempted to induce brain MT in rats by exposure to methylmercury
      (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood
      brain barrier and cause neurological damage. Rats treated with MeHg (40
      micromol/kg per day x 5 days, p.o.) showed brain Hg levels as high as 18 microg/g
      with slight neurological signs 10 days after final administration, but brain MT
      levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7
      8 microg Hg/g brain tissue 24 h after cessation of exposure. At that time brain
      MT levels were about twice the control levels. Although brain Hg levels fell
      gradually with a half-life of 26 days, MT levels induced by Hg exposure remained
      unchanged for > 2 weeks. Gel fractionation revealed that most Hg was in the brain
      cytosol fraction and thus bound to MT. Hybridization analysis showed that,
      despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was
      less affected. Although significant Hg accumulation and MT induction were
      observed also in kidney and liver of Hg vapor-exposed rats, these decreased more
      quickly than in brain. The long-lived MT in brain might at least partly be
      accounted for by longer half-life of Hg accumulated there. The present results
      showed that exposure to Hg vapor might be a suitable procedure to provide an in
      vivo model with enhanced brain MT.

PMID- 9587012
TI  - Methylmercury inhibits gap junctional intercellular communication in primary
      cultures of rat proximal tubular cells.
AB  - Methylmercury (MeHg) causes renal injury in addition to central and peripheral
      neuropathy. To clarify the mechanism of nephrotoxicity by MeHg, we investigated
      the effect of this compound on intercellular communication through gap junction
      channels in primary cultures of rat renal proximal tubular cells. Twenty minutes
      after exposure to 30 microM MeHg, gap junctional intercellular communication
      (GJIC), which was assessed by dye coupling, was markedly inhibited before
      appearance of cytotoxicity. When the medium containing MeHg was exchanged with
      MeHg-free medium, dye coupling recovered abruptly. However, the dye-coupling was
      abolished again 30 min after replacement with control medium, and the cells were
      damaged. Intracellular calcium concentration, [Ca2+]i, which modulates the
      function of gap junctions, significantly increased following exposure of the
      cells to 30 microM MeHg and returned to control level following replacement with
      MeHg-free medium. These results suggest that the inhibiting effect of MeHg on
      GJIC is related to the change in [Ca2+]i, and may be involved in the pathogenesis
      of renal dysfunction.

PMID- 9587013
TI  - Glutathione modifies the toxicity of triethyltin and trimethyltin in C6 glioma
      cells.
AB  - It has been demonstrated that exposure to mercury or cadmium compounds causes
      alterations in the glutathione system in a model glial cell line, C6. Here we
      report that two organic tin compounds, triethyltin (TET) and trimethyltin (TMT),
      are also toxic to these cells with EC50 values for cell death of c. 0.02 microM
      and 0.8 microM respectively. Exposure for 24 h to either of these compounds at
      sub-toxic concentrations caused increases in the amount of reduced glutathione
      (GSH) per cell. Increases in glutathione-S-transferase enzyme activity were also
      demonstrated after TET or TMT exposure. This suggests that glutathione increases
      occur in glial cells after toxic insults below that required to cause cell death,
      possibly acting as a protective mechanism. To test whether GSH plays a role in
      organotin-induced cell death we manipulated GSH in the culture media or via
      intracellular GSH and looked at the effects on sensitivity to TET or TMT
      toxicity. Adding GSH to the culture media did not protect the cells. Depletion of
      intracellular GSH with buthionine-[S,R] sulphoximine did not alter cytotoxicity
      of TET or TMT. However, pre-treatment with (-)-2-oxo-4-thiazolidine carboxylic
      acid (OTC), which increases intracellular GSH levels, protected the cells against
      both compounds. The EC50 for TMT was increased from 0.77 to 1.8 microM, a 2.3
      fold shift, whereas the EC50 for TET was increased > 20-fold, from 0.022 to 0.47
      microM. One interpretation of these results is that GSH protects cells against
      the toxicity of organic tin compounds without reacting directly with them to any
      significant extent. Under conditions where GSH is depleted, additional protective
      mechanisms may be active.

PMID- 9587014
TI  - An immunological method for the detection of captopril-protein conjugate.
AB  - To clarify the mechanism of cytotoxicity induced by captopril (Cp), interactions
      between tissue protein and Cp were studied by the enzyme-linked immunosorbent
      assay (ELISA) method. The amide-linked adducts [hemocyanin from keyhole limpet-Cp
      adduct (KLH-Cp) and poly-L-Lys-Cp adduct (pLys-Cp)] using carbodiimide, and a
      disulfide-linked adduct [ovalbumin-Cp adduct (OVA-Cp)] were prepared. To
      determine the formation of the protein-Cp adduct, rabbit antisera against KLH-Cp
      was employed. The immunoreactivities with pLys-Cp and OVA-Cp against anti KLH-Cp
      sera were elevated when compared with the unmodified protein. With the inhibition
      ELISA, this antisera was useful for detecting the Cp disulfide-linked conjugate.
      In kidney cytosol, a high level of immunoreactivity was observed. Plasma and
      liver cytosol reactivities were similar, and approximately 40% against kidney
      cytosol. Thus, a method for the detection of the Cp-protein adduct using ELISA
      has been established. Formation of the Cp-protein adduct was observed in rat
      plasma and in liver and kidney cytosol. These findings suggest the possibility
      that the formation of Cp-protein adduct is partially related to cytotoxicity in
      liver.

PMID- 9587016
TI  - High frequency of CYP1A1 mutations in a Turkish population.
AB  - The frequency distribution of four cytochrome P4501A1 (CYP1A1) gene mutations was
      investigated in 271 Turks from southeast Anatolia by polymerase chain
      reaction/restriction fragment length polymorphism (PCR/RFLP) assay. Allelic
      linkage of those mutations was proven by peptide nucleic acid-mediated PCR
      clamping. Mutation ml (T6235C) forming an MspI restriction site in the 3'
      flanking region occurred with 18.1% frequency (95% confidence interval 14.9
      21.6%), m2 (A4889G) leading to an Ile/Val exchange in exon 7 had a frequency of
      8.9% (6.6-11.6%), and m4 (C4887A; Thr/Asn-exchange also in exon 7) occurred with
      5.7% (3.9-8.0%). T5639C (m3) in the 3'-flanking region was not detected. m2 was
      exclusively found linked with ml forming allele CYP1A1*2B. The frequency of this
      allele supposedly at-risk for lung cancer was significantly higher than in Middle
      European populations, but lower than in the Far East.

PMID- 9587015
TI  - Oxidation of methyl- and ethyl- tertiary-butyl ethers in rat liver microsomes:
      role of the cytochrome P450 isoforms.
AB  - Methyl t-butyl ether (MTBE) and ethyl t-butyl ether (ETBE) are commonly used in
      unleaded gasoline to increase the oxygen content of fuel and to reduce carbon
      monoxide emissions from motor vehicles. This study was undertaken to investigate:
      (1) the effect of administration to rats of ETBE and its metabolite, t-butanol,
      on the induction and/or inhibition of hepatic P450 isoenzymes; (2) the oxidative
      metabolism of MTBE and ETBE by liver microsomes from rats pretreated with
      selected P450 inducers and purified rat P450(s), (2B1, 2E1, 2C11, 1A1). ETBE
      administration by gavage at a dose of 2 ml/kg for 2 days induced hepatic
      microsomal P4502E1-linked p-nitrophenol hydroxylase and the P4502B1/2-associated
      PROD and 16beta-testosterone hydroxylase, verified by immunoblot experiments. t
      Butanol treatments at doses of 200 and 400 mg/kg i.p. for 4 days did not alter
      any liver microsomal monoxygenases. Both MTBE and ETBE were substrates for rat
      liver microsomes and were oxidatively dealkylated to yield formaldehyde and
      acetaldehyde, respectively. The dealkylation rates of both MTBE and ETBE were
      increased c. fourfold in phenobarbital (PB)-treated rats. In rats pretreated with
      pyrazole, an inducer of 2E1, only the demethylation of MTBE was increased (c.
      twofold). When the oxidations of MTBE and ETBE were investigated with purified
      P450(s) in a reconstituted system, it was found that P4502B1 had the highest
      activities towards both solvents, whereas 1A1 and 2C1 were only slightly active;
      P4502E1 had an appreciable activity on MTBE but not against ETBE. Metyrapone, a
      potent inhibitor of P450 2B, consistently inhibited both the MTBE and ETBE
      dealkylations in microsomes from PB-treated rats. Furthermore, 4-methylpyrazole
      (a probe inhibitor of 2E1) and anti-P4502E1 IgG showed inhibition, though modest,
      only on MTBE demethylation, but not on ETBE deethylation. Inhibition experiments
      have also suggested that rat 2A1 may exert an important role in MTBE and ETBE
      oxidation. Taken together, these results indicate that 2B1, when expressed, is
      the major enzyme involved in the oxidation of these two solvents and that 2E1 may
      have a role, although minor, in MTBE demethylation. The implications of these
      data for MTBE and ETBE toxicity remain to be established.

PMID- 9587017
TI  - Phosphotriesterase activity identified in purified serum albumins.
AB  - The phosphotriesterase in chicken serum that hydrolyses O-hexyl O-2,5
      dichlorophenyl phosphoramidate (HDCP) was purified in three chromatographic
      steps. The activity copurified to apparent homogeneity with albumin monitoring by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS/ PAGE) and by SDS
      capillary electrophoresis in the purified fractions. Commercial chicken serum
      albumin was further purified and the phosphotriesterase activity remained
      associated with albumin. Capillary electrophoresis established a molecular weight
      of 59 +/- 4 kDa for both purified proteins (chicken serum and commercial chicken
      serum albumin). The purified samples were assayed for hydrolytic activity against
      several carboxylesters, organophosphates and phosphoramidates. From
      carboxylesters, only p-nitrophenylbutyrate (p-NPB) hydrolysing activity was found
      to copurify with the phosphotriesterase. The purified human, chicken, rabbit and
      bovine serum albumins and recombinant human serum albumin obtained from
      commercial sources hydrolysed HDCP and p-NPB. Serum albumin also hydrolysed O
      butyl O-2,5-dichlorophenyl phosphoramidate, O-ethyl O-2,5-dichlorophenyl
      phosphoramidate and O-2,5-dichlorophenyl ethylphosphonoamidate but not other
      organophosphates and phosphoramidates.

PMID- 9587018
TI  - An algorithm for nasal pungency thresholds in man.
AB  - Nasal pungency thresholds (NPT) in man have been determined by Cometto-Muniz and
      Cain for 44 varied compounds, including esters, aldehydes, ketones, alcohols,
      carboxylic acids, aromatic hydrocarbons and pyridine. With the exclusion of
      acetic acid, 43 of these NPT values are well correlated through the general
      linear free energy equation of Abraham, leading to the algorithm, log(1/NPT) = 
      8.519 + 2.154 pi(2)H + 3.522 sigma alpha(2)H + 1.397 sigma beta(2)H + 0.860
      logL16. N = 43, r2 = 0.955, SD = 0.27, F = 201 (i) where the independent
      variables are solute descriptors: pi(2)H is the dipolarity/polarizability, sigma
      alpha(2)H and sigma beta(2)H are the overall or effective hydrogen-bond acidity
      and basicity, and L16 is the solute Ostwald solubility coefficient on hexadecane
      at 25 degrees C. Surprisingly, the aliphatic aldehydes and carboxylic acids fit
      the correlation and with respect to nasal pungency thresholds in man for brief (1
      3 s) presentations must be regarded as 'nonreactive' compounds. It is suggested
      mere transport of the compound from the air stream to the receptor area largely
      determines the potency to produce pungency. Various chemical properties of the
      receptor area are deduced from the coefficients in Eq. i.

PMID- 9587019
TI  - Cytotoxicity of fumonisin B1: implication of lipid peroxidation and inhibition of
      protein and DNA syntheses.
AB  - The effects of fumonisin B1 (FB1) from Fusarium moniliforme on lipid peroxidation
      and protein and DNA syntheses were studied in monkey kidney cells (Vero cells).
      FB1 was found to be a potent inducer of malondialdehyde (MDA), one of the
      secondary products formed during lipid peroxidation. At 0.14 microM (0.1
      microg/ml), FB1 induced 0.496 +/- 0.1 nmoles of MDA/ mg protein, compared to the
      control level 0.134 +/- 0.01 nmoles of MDA/mg protein (P < 0.005). No inhibition
      of protein or DNA synthesis was observed at this concentration of FB1. Inhibition
      of protein and DNA syntheses was observed at FB1 concentrations > 14 microM (10
      microg/ml) with an IC50 of 33 microM for both protein synthesis and DNA
      synthesis. These results indicate that lipid peroxidation is a very sensitive
      cellular response to the mycotoxin fumonisin B1 observed at concentrations lower
      than that required to inhibit cellular synthesis of macromolecules, protein and
      DNA. This oxidative damage induced by FB1 concentrations encountered in naturally
      contaminated foodstuffs and feed might lead to mutagenicity and genotoxicity.

PMID- 9587020
TI  - Reactivating potency of obidoxime, pralidoxime, HI 6 and HLo 7 in human
      erythrocyte acetylcholinesterase inhibited by highly toxic organophosphorus
      compounds.
AB  - The treatment of poisoning by highly toxic organophosphorus compounds (nerve
      agents) is unsatisfactory. Until now, the efficacy of new potential antidotes has
      primarily been evaluated in animals. However, the extrapolation of these results
      to humans is hampered by species differences. Since oximes are believed to act
      primarily through reactivation of inhibited acetylcholinesterase (AChE) and
      erythrocyte AChE is regarded to be a good marker for the synaptic enzyme, the
      reactivating potency can be investigated with human erythrocyte AChE in vitro.
      The present study was undertaken to evaluate the ability of various oximes at
      concentrations therapeutically relevant in humans to reactivate human erythrocyte
      AChE inhibited by different nerve agents. Isolated human erythrocyte AChE was
      inhibited with soman, sarin, cyclosarin, tabun or VX for 30 min and reactivated
      in the absence of inhibitory activity over 5-60 min by obidoxime, pralidoxime, HI
      6 or HLo 7 (10 and 30 microM). The AChE activity was determined photometrically.
      The reactivation of human AChE by oximes was dependent on the organophosphate
      used. After soman, sarin, cyclosarin, or VX the reactivating potency decreased in
      the order HLo 7 > HI 6 > obidoxime > pralidoxime. Obidoxime and pralidoxime were
      weak reactivators of cyclosarin-inhibited AChE. Only obidoxime and HLo 7
      reactivated tabun-inhibited AChE partially (20%), while pralidoxime and HI 6 were
      almost ineffective (5%). Therefore, HLo 7 may serve as a broad-spectrum
      reactivator in nerve agent poisoning at doses therapeutically relevant in humans.

PMID- 9587021
TI  - Expiration of ethane in rats under variously elevated inspiratory O2
      concentrations.
AB  - Expired ethane is regarded as a noninvasive indicator of lipid peroxidation. As a
      model of oxidative stress we have investigated in male Wistar rats (body wt. 309
      +/- 15 g) the effects of various levels of elevated inspiratory oxygen
      concentrations on the expiration rate of ethane. After 4 days under 21 vol% O2
      (basic condition) the rats were exposed for 6 or 5 days to 40, 60 or 80 vol% O2
      over 8 or 23 h/day. The variously O2-enriched air was conducted through the cages
      and expired ethane adsorbed onto charcoal was thermo-desorbed and measured by gas
      chromatography. Basic ethane expiration was 3.1 +/- 0.8 pmol/100 g body wt. per
      min. At 40 vol% O2 over 8 or 23 h/day no increase or a maximum average 47%
      increase (P < 0.01) in ethane expiration occurred on day 4; 60 vol% O2 over 8 or
      23 h/day led to a corresponding increase of 56 or 87% (P < 0.05 or P < 0.01) on
      day 3; 80 vol% O2 over 8 or 23 h/day led to a corresponding increase of 81 or 66%
      (P < 0.01) on days 3 or 2. Our results indicate that with up to 60 vol% O2 a
      temporary increase in lipid peroxidation occurs in a dose dependent manner.
      However, at 80 vol% O2 no further increase in the maximum ethane expiration
      occurred. The latter finding and the finding of only transient increase in ethane
      expiration in probably due to antioxidative counteraction.

PMID- 9587022
TI  - Induction of single-strand breaks in lymphocyte DNA of rats exposed to hyperoxia.
AB  - A modified technique of alkaline filter elution was used to evaluate single
      strand breaks (SSB) as a measure of DNA lesions in lymphocytes of male Wistar
      rats exposed to 60 or 80 vol% oxygen, over 23 h/day and for 6 or 5 days,
      respectively. An acceleration of elution was observed with samples from
      experiments at both increased levels of oxygen. With proteinase K treatment, a
      twofold increase in elution rates after exposure to 60 vol% oxygen and a
      threefold increase at 80 vol% oxygen were indicative of increased occurrence of
      SSB. This is explained by an involvement of reactive oxygen species in DNA damage
      under elevated oxygen levels.

PMID- 9587023
TI  - Disorders of homocysteine metabolism: from rare genetic defects to common risk
      factors. Proceedings of an international symposium. Fulda, Germany, 20-22
      November 1996.

PMID- 9587024
TI  - The metabolism of homocysteine: pathways and regulation.
AB  - Two pathways, the methionine cycle and transsulfuration, account for virtually
      all methionine metabolism in mammals. Every tissue possesses the methionine
      cycle. Therefore, each can synthesize AdoMet, employ it for transmethylation,
      hydrolyze AdoHcy, and remethylate homocysteine. Transsulfuration, which occurs
      only in liver, kidney, small intestine and pancreas, is the means for
      catabolizing homocysteine. Liver has a unique isoenzyme of MAT that allows the
      utilization of excess methionine for the continued synthesis of AdoMet. Metabolic
      regulation is based on the distribution of available homocysteine between
      remethylation and conversion to cystathionine. The tissue content of the enzymes
      and their inherent kinetic properties provide the basis for the regulatory
      mechanism. The effector properties of the metabolites AdoMet, AdoHcy and
      methylTHF are of particular relevance.

PMID- 9587025
TI  - Hyperhomocysteinemia in terms of steady-state kinetics.
AB  - The plasma level of homocysteine (Hcy) and its oxidized products, i.e., plasma
      total Hcy (tHcy), is a function of the influx rate of Hcy to plasma and the
      plasma tHcy clearance. In vitro experiments show that proliferating cells usually
      export more Hcy than stationary cells and that the Hcy export increases in
      response to high methionine, low folate or low cobalamin level, and to agents
      interfering with Hcy remethylation. Comparison between various cell types
      suggests that hepatocytes have a unique ability to increase the Hcy export in
      response to extracellular methionine, probably due to its capacity to form
      adenosylmethionine. Some but not all cell types have an ability to use
      extracellular Hcy as a methionine source. Clearance studies in healthy subjects
      indicate that about 1.2 mmol Hcy is supplied from the cells to plasma per 24 h,
      which is only about 5-10% of total Hcy formed. Comparison of area under the
      curves after administration of Hcy and methionine shows that about 10% of the
      methionine administered is released to plasma as Hcy. Notably, only a few percent
      of Hcy from plasma is excreted unchanged in the urine, and this shows that most
      tHcy in plasma is metabolized. Folate or cobalamin deficient patients have normal
      plasma tHcy clearance, which suggests that their elevated tHcy level is due to
      increased Hcy export from tissues into the plasma compartment. In contrast, the
      hyperhomocysteinemia in renal failure is accounted for by a marked reduction in
      tHcy clearance, suggesting an important role of kidney in elimination of Hcy from
      plasma.

PMID- 9587026
TI  - Biochemistry and molecular genetics of cystathionine beta-synthase deficiency.
AB  - Homocysteine is an independent risk factor for arteriosclerotic disease.
      Deficiency of cystathionine beta-synthase (CBS) is the major cause of inherited
      homocysteinemia. The CBS gene is 25-30 kbp long and encodes a subunit of 63 kDa.
      The active form of the enzyme is a homotetramer that contains one heme and one
      pyridoxal 5'-phosphate per each subunit. It can also bind 1 mol of S
      adenosylmethionine per mol of subunit. To date, an analysis of 205 homocystinuric
      alleles has been performed and 64 mutations found. The best studied, relatively
      "homogeneous" patient populations are those of Ireland, Holland, and Italy. While
      the overall frequency of the two most frequent mutations is 24% for I278T and 31%
      for G307S, the breakdown between the countries varies greatly. For instance, the
      B6-nonresponsive G307S mutation accounts for > 70% alleles in Ireland and B6
      responsive I278T mutation on the continent approaches 45%. In conclusion, further
      research is needed to define the mutations in individual countries to facilitate
      screening and genotype/phenotype correlations. Future biochemical studies will
      likely elucidate the role of heme in the enzyme and the tertiary structure of
      CBS.

PMID- 9587027
TI  - Methylenetetrahydrofolate reductase and methionine synthase: biochemistry and
      molecular biology.
AB  - Methylenetetrahydrofolate reductase and cobalamin-dependent methionine synthase
      catalyze the penultimate and ultimate steps in the biosynthesis of methionine in
      prokaryotes, and are required for the regeneration of the methyl group of
      methionine in mammals. Defects in either of these enzymes can lead to
      hyperhomocysteinemia. The sequences of the human methylenetetrahydrofolate
      reductase and methionine synthase are now known, and show clear homology with
      their bacterial analogues. Mutations in both enzymes that are known to occur in
      humans and to be associated with hyperhomocysteinemia affect residues that are
      conserved in the bacterial enzymes. Structure/function studies on the bacterial
      proteins, summarized in this review, are therefore relevant to the function of
      the human enzymes; in particular studies on the effects of bacterial mutations
      analogous to those causing hyperhomocysteinemia in human may shed light on the
      defects associated with these mutations.

PMID- 9587029
TI  - Clinical aspects of cystathionine beta-synthase deficiency: how wide is the
      spectrum? The Italian Collaborative Study Group on Homocystinuria.
AB  - Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is an
      autosomal recessive disease of sulphur amino acid metabolism. Major clinical
      manifestations include disorders of the eye, the skeleton, the central nervous
      system and the vascular system. A wide clinical spectrum of the disease has been
      reported. We discuss the role of genetic factors (e.g. different mutations of the
      CBS gene and a variable genetic background) and the importance of environmental
      factors (e.g. diet, vitamins, perinatal factors and drugs) in explaining the
      phenotypic variability observed in homocystinuria. CONCLUSION: Homocystinuria
      represents a good model to explain the clinical differences frequently observed
      among patients affected by monogenic diseases.

PMID- 9587028
TI  - Genetic defects of folate and cobalamin metabolism.
AB  - Deficient activity of an enzyme can result from a defect in the conversion of the
      vitamin to a co-enzyme as well from an abnormal apo-enzyme or disturbed binding
      of coenzyme to enzyme. Conversion of dietary vitamin to intracellular active co
      enzyme can be complex and require many physiological and biochemical processes
      including stomach release of bound vitamin, intestinal uptake,
      carriers/transport, blood transport, cellular uptake, intracellular release and
      intracellular compartmentalisation. Disorders of malabsorption (food cobalamin
      malabsorption, intrinsic factor deficiency and abnormal enterocyte cobalamin
      processing) and transport proteins (transcobalamin II deficiency, R-binder
      deficiency) mostly lead to disturbed function of the two cobalamin requiring
      enzymes, methylmalonyl CoA mutase and methionine synthase. Defects of early steps
      of intracellular cobalamin (cblF, cbl C/D) result in marked deficiencies of both
      cobalamin co-enzymes and homocystinuria combined with methylmalonic aciduria.
      Defective synthesis of adenosyl cobalamin in the cbl A/B defects leads to
      methylmalonyl CoA mutase. Isolated methionine synthase deficiency is also
      classified as a cobalamin disorder due to its associated deficient formation of
      methylcobalamin. Folate disorders include methylene-tetrahydrofolate reductase
      deficiency and glutamate formimino-transferase deficiency. In addition a
      hereditary disorder of intestinal folate transport has been described. Less well
      established are disorders of dihydrofolate reductase, methenyl-tetrahydrofolate
      cyclohydrolase, and defects of cellular folate uptake.

PMID- 9587030
TI  - Strategies for the treatment of cystathionine beta-synthase deficiency: the
      experience of the Willink Biochemical Genetics Unit over the past 30 years.
AB  - Strategies for the treatment of cystathionine beta-synthase (CBS) deficiency
      include (1) increasing residual enzyme activity by giving pyridoxine in those
      patients with vitamin responsive variants, (2) reducing the load on the affected
      pathway with a low methionine diet and supplementing the diet with cysteine; and
      (3) giving betaine in order to utilise alternative pathways to remove
      homocyst(e)ine. In our experience of over 30 years in the diagnosis and
      management of patients with CBS deficiency, a normal outcome can only be achieved
      in patients diagnosed and treated from infancy. Pyridoxine combined with folic
      acid prevents further deterioration in pyridoxine responsive patients. Dietary
      treatment of patients with non-pyridoxine responsive CBS deficiency becomes more
      difficult outside childhood but since late complications are not uncommon must be
      continued for life. Betaine can be effective in this group but compliance is
      often poor.

PMID- 9587031
TI  - Remethylation defects: guidelines for clinical diagnosis and treatment.
AB  - The main remethylation defects include disorders which all have defective
      methionine synthesis in common. Methylenetetrahydrofolate reductase deficiency
      impairs methyltetrahydrofolate synthesis, defects in cytosolic reduction of
      hydroxocobalamin (CblC/D) impair the synthesis of both methyl- and adenosyl
      cobalamin and deficiencies of methionine synthase (CblE/G) are associated with
      defective methyl cobalamin synthesis. The clinical presentation is characterized
      by acute neurological distress in early infancy. In childhood, patients present
      with progressive encephalopathy with an end-stage which has many signs in common
      with the adult onset form. In fact, both have more or less severe signs of
      subacute degeneration of the cord. Cobalamin defective patients must be treated
      with parenteral supplementation of hydroxocobalamin (1-2 mg per dose). Some
      methylenetetrahydrofolate patients could be folate responsive and must have a
      high-dosage folate trial. In addition, oral betaine supplementation (2-9 g per
      day depending on age) appears an effective means to prevent further neurological
      deterioration.

PMID- 9587032
TI  - Newborn screening for homocystinuria: Irish and world experience.
AB  - Newborn screening for cystathionine beta-synthase deficiency (homocystinuria;
      HCU) was started in the late 1960s using a bacterial inhibition assay (BIA). At
      least seven countries have either national or regional screening programmes; 12
      programmes are known to have discontinued. The worldwide incidence of HCU is
      approximately 1 in 335,000 but varies from 1:65,000 (Ireland) to 1:900,000
      (Japan). Methodologies include the BIA, one-dimensional or thin-layer amino acid
      chromatography and, more recently, tandem mass spectrometry. The BIA diagnostic
      cut off concentration of blood methionine varies from 67 to 270 micromol/ (10-40
      mg/l) with a median of 135 micromol/l (20 mg/l). In Ireland, 25 cases of HCU from
      19 families have been identified from 1.58 million newborn infants since 1971; 21
      cases were detected through the screening programme. Of the four missed cases,
      three were breast-fed at the time of blood collection and one was pyridoxine
      responsive. These findings were in broad agreement with the results from five
      other programmes, in which approximately one in every five cases was missed by
      the screening programme. Early hospital discharge, low protein intake, high blood
      methionine cut-off concentration and pyridoxine responsiveness were all
      identified as contributing to missed cases.

PMID- 9587033
TI  - Post- and prenatal diagnostic methods for the homocystinurias.
AB  - Diagnosis of the homozygous homocystinurias can be performed by investigations at
      the metabolite, enzyme and DNA level. The existence of variant forms due to the
      wide range of genetic variation may result in only small differences in various
      parameters between controls and affected subjects. 1. Sulphur amino acid
      concentrations in plasma, especially total homocysteine, are useful in first line
      diagnostic investigations. 2. Cystathionine-beta-synthase (CBS),
      methylenetetrahydrofolate reductase (MTHFR) and methylfolate homocysteine
      methyltransferase (MFMT) can be directly assayed in many tissues including
      fibroblasts (each) and blood cells (except CBS). Indirect whole cell assays which
      measure pathway activity dependent on a particular enzyme can provide useful
      diagnostic information. 3. Direct analysis of mutations is available for CBS,
      MTHFR and recently also for MFMT deficiencies. However the existence of a larger
      number of very rare, often private, mutations limits the usefulness of this
      approach in routine diagnosis. The above diagnostic approaches can generally be
      applied to prenatal diagnosis. Measurement of methylmalonic acid and other
      metabolites in amniotic fluid by stable isotope dilution / gas chromatography
      mass spectrometry is well established for the methylmalonic acidurias. This
      method has also been applied to combined homocystinuria/methylmalonic aciduria
      supported by enzyme assays in cultured cells. Total homocysteine measurement in
      cell free amniotic fluid is also possible, performed so far in 14 cases with two
      affected fetuses. The indirect assay of methionine formation from [14C] labelled
      formate in intact cultured amniotic fluid cells has been for prenatal diagnosis
      of the remethylation defects.

PMID- 9587034
TI  - Ocular complications and a new surgical approach to lens dislocation in
      homocystinuria due to cystathionine-beta-synthetase deficiency.
AB  - The ocular findings in patients with homocystinuria due to cystathionine-beta
      synthetase (CBS) deficiency are reviewed and a new approach to lens surgery is
      presented. Lens surgery in CBS deficiency was reported to be accompanied by a
      high risk of secondary complications like vitreal prolapse and retinal
      detachment. So far an operative procedure for these patients that allows a
      complete preservation of the anterior vitreous cortex, the posterior lens capsule
      and an implantation of an artificial lens is not established. A minimal invasive
      method of lens surgery was developed in vitro and applied in the case of a 10
      year-old patient with an uncorrectable refractive situation due to progressed
      lens dislocation. Principle steps of the evolved operative procedure are (1)
      visco-elastic stabilization of the anterior chamber; (2) small (1.5 mm)
      peripheral capsulorhexis; (3) manual endocapsular aspiration of lens material and
      removal of lens epithelium; (4) ab externo introduction of a transcleral fixation
      suture; (5) positioning of the haptic into the ciliary sulcus in the inferior
      position; (6) resection of the anterior lens capsule; and (7) positioning of the
      second haptic into the ciliary sulcus. The first patient treated according to
      this method presented a stable position of the pseudophakos during the follow up
      of 1 year. Visual acuity improved from a level of 20/200 (O.D.) and 10/200 (O.S.)
      to 18/20 in both eyes. The surgical procedure presented in this report seems to
      be useful for dealing with dislocated lenses due to zonular deficiency in
      patients with CBS deficiency and hopefully with Marfan disease. It allows a
      minimal invasive removal of the lens, a complete preservation of the anterior
      vitreous cortex and at the same time a stable fixation of an artificial
      intraocular lens.

PMID- 9587035
TI  - The redox status of aminothiols as a clue to homocysteine-induced vascular
      damage?
AB  - Vascular disease associated with increased blood concentrations of homocysteine
      has been known for many years. However, the pathobiochemical mechanisms leading
      to vasculopathy are still unknown. Several attempts have been made to establish
      in vitro model systems for the evaluation of homocysteine specific effects in
      cultured cells. It was concluded from these experiments, that
      hyperhomocysteinemia has to be considered as a risk factor for atherosclerosis
      exerting its effects mainly by mechanisms involving oxidative damage. Here, we
      summarize the homocysteine induced cellular effects which may be due to
      alterations of the redox thiol status. Effects specific for homocysteine are
      demonstrated working on different levels of cellular processes involving protein
      folding and regulation of nuclear factor kappaB (NF-kappaB) controlled gene
      transcription, the latter opening a new perspective for a novel pathway by which
      homocysteine might enhance chronic inflammation of the endothelium and possibly
      contributes to the development of atherosclerosis.

PMID- 9587036
TI  - Abnormalities of vascular function in hyperhomocysteinaemia: relationship to
      atherothrombotic disease.
AB  - Hyperhomocysteinaemia is a risk factor for atherothrombotic disease, but data are
      limited on the arterial histology in humans with hyperhomocysteinaemia, either
      with or without other risk factors. Studies in vitro and in animals have shown
      that hyperhomocysteinaemia, possibly by increasing oxidant stress as well as by
      other mechanisms, may induce dysfunction of the vascular endothelium and
      proliferation of vascular smooth muscle cells, both key processes in
      atherogenesis. In clinically healthy subjects with hyperhomocysteinaemia,
      endothelium-dependent vasodilation may be impaired, but endothelial
      antithrombotic and profibrinolytic function appear normal at this stage. In
      patients with atherosclerosis and hyperhomocysteinaemia, endothelial
      antithrombotic properties appear more severely impaired than in similar patients
      with normohomocysteinaemia. Controlled data on the effects of homocysteine
      lowering treatment on vascular function in humans are not available. The
      increased risk of atherothrombotic disease conferred by hyperhomocysteinaemia may
      be related to homocysteine-associated impairments in endothelial and vascular
      smooth muscle cell function. The precise mechanisms by which homocysteine affects
      vascular cell function, however, are unknown.

PMID- 9587037
TI  - Homocysteic and homocysteine sulphinic acid exhibit excitotoxicity in organotypic
      cultures from rat brain.
AB  - The excitotoxic action of homocysteine and related sulphur-containing metabolites
      was investigated in organotpyic cultures derived from rat brain cortex and
      hippocampus by inhibition experiments using antagonists selective for different
      glutamate receptor subtypes. In addition the direct interaction of these
      metabolites with glutamate receptors expressed in frog oocytes was tested by
      conventional two electrode voltage clamp techniques. CONCLUSION:
      Neurodegeneration and epilepsy observed in homocystinuria may be mediated by L
      homocysteic and L-homocysteine sulphinic acid. Both metabolites exhibit
      excitotoxic potency by interaction with different glutamate receptor subtypes.

PMID- 9587038
TI  - Demyelination and inborn errors of the single carbon transfer pathway.
AB  - Inborn errors of the single-carbon transfer pathway are rare disorders of folate
      and cobalamin metabolism. They may be complicated by demyelination resembling
      subacute combined degeneration of the cord and brain. The study of CSF
      metabolites in children with serial errors affecting the single-carbon transfer
      pathway has suggested that S-adenosylmethionine deficiency is a cause of the
      demyelination. This deficiency is corrected by treatment that causes clinical
      improvement and remyelination. Some treatments can only have an indirect effect
      on the brain and this is discussed with other evidence that the liver may produce
      factors that are necessary for the maintenance of central myelin.

PMID- 9587039
TI  - Relevance of vitamins, homocysteine and other metabolites in neuropsychiatric
      disorders.
AB  - Indistinguishable hematologic abnormalities are seen in most patients with
      cobalamin (Cbl, vitamin B12) or folate deficiency. Approximately one third of Cbl
      deficient patients develop a wide variety of non-focal neuropsychiatric
      abnormalities that are not seen in folate deficiency. Serum levels of
      homocysteine are elevated to a similar degree in Cbl-deficient patients with and
      without neuropsychiatric abnormalities, and in folate-deficient patients. Serum
      levels of eight other metabolites including methylmalonic acid also fail to
      elucidate the biochemical basis for the neuropsychiatric abnormalities. Levels of
      homocysteine and methylmalonic acid are often only slightly elevated in Cbl
      deficient patients who have significant neuropsychiatric defects. Moderate
      elevations of homocysteine and methylmalonic acid occur in 20%-30% of various
      elderly populations (mean age 80) and may play a role in the similar
      neuropsychiatric abnormalities that occur increasingly with aging. Taken
      together, these studies suggest that an important unknown Cbl-dependent enzyme,
      metabolic abnormality, environmental factor, or genetic factor may play a major
      role in the pathophysiology of the neuropsychiatric abnormalities caused by Cbl
      deficiency.

PMID- 9587040
TI  - Moderate hyperhomocysteinaemia and vascular disease: evidence, relevance and the
      effect of treatment.
AB  - Convincing evidence of moderate hyperhomocysteinaemia as a risk factor for
      vascular disease has accumulated within the last decade being independent of
      conventional risk factors and equally strong as hypercholesterolaemia and
      smoking. A synergistic interaction with hypertension and smoking in their joint
      arteriosclerotic effect in patients is demonstrated which makes the result of
      homocysteine-lowering intervention very promising, especially in those vascular
      patients with an association of these risk factors. CONCLUSION: Despite the
      proven homocysteine-lowering effect of intervention with sample, safe, and cheap
      vitamin regimen, no data are so far available on the clinical outcome of such
      treatment. Clinical trials to demonstrate a hopefully beneficial result of
      homocysteine reduction are urgently needed.

PMID- 9587041
TI  - Mutated 5,10-methylenetetrahydrofolate reductase and moderate
      hyperhomocysteinaemia.
AB  - Moderate hyperhomocysteinaemia (MHH) is a risk factor for arteriosclerosis and
      thrombosis. About 10%-20% of the normal population have homocysteine levels
      contributing to an increased risk for arterial and venous disease. Main
      regulating enzymes of homocysteine metabolism are cystathionine beta-synthase
      (CBS) and methylenetetrahydrofolate reductase (MTHFR). Heterozygosity for CBS
      deficiency is most likely not an important cause for MHH in vascular disease. A
      recently discovered cause of MHH is reduced MTHFR activity due to a homozygous
      C677T mutation in the coding region of MTHFR. This mutation has been related to
      an increased risk for cardiovascular disease, although a number of studies are
      not confirmative. The elevated homocysteine levels due to this mutation can be
      normalized by administration of vitamins involved in homocysteine metabolism, in
      particular folate.

PMID- 9587042
TI  - Vitamins B12, B6 and folate as determinants of homocysteine concentration in the
      healthy population.
AB  - The metabolism of a substrate is closely linked to that of its cofactor(s). In
      the case of homocysteine, the vitamins B12, B6 and folic acid are involved in its
      metabolism, acting as coenzymes. To evaluate the role of these vitamins as
      determinants of homocysteine concentration in the healthy population, only data
      from this group should be considered. Studies dealing with vitamin deficiency and
      the occurrence of elevated homocysteine levels as well as with the treatment of
      elevated homocysteine levels by supplementing one or more of the vitamins have to
      be omitted. In the healthy population with "normal" homocysteine levels and a
      vitamin status currently regarded as adequate, folate seems to play the most
      important role in determining the blood homocysteine level. This has been derived
      from supplementation studies as well as from statistical correlation analysis
      regarding the relationship of the three vitamins to homocysteine. Until now,
      recommended dietary allowances for folate have been defined on the basis of the
      absence of clinical signs of deficiency as well as morphological alterations of
      blood cells indicating an early stage of folate deficiency. However, these
      recommended dietary allowance values do not seem to be sufficient when looking at
      homocysteine as a functional parameter of folate status. Due to the important
      role of folate status as a determinant of homocysteine concentration, it may be
      necessary to redefine an adequate blood folate level and probably reformulate
      dietary allowances for this B-vitamin.

PMID- 9587043
TI  - Neural tube defects, vitamins and homocysteine.
AB  - Folic acid (multivitamins) reduce the recurrence and occurrence of neural tube
      defects (NTDs). Vitamin profiles seem not suitable to identify women at risk for
      NTDs. A subset of these women have hyperhomocysteinaemia and a mutation of the
      gene for thermolabile methylenetetrahydrofolate reductase (MTHFR). From studies
      with the rat embryo in vitro, it can be concluded that the de- and remethylation
      cycle of methionine, being folate and vitamin B12 dependent, is crucial for
      embryonic and fetal growth probably via generation of DNA, proteins and
      polyamines. Nutrition for the embryo is also supplied by the follicular fluid,
      the yolk sac, the extraembryonic coelomic cavity and the amniotic fluid.

PMID- 9587044
TI  - Pharmacological management of epilepsy. Mechanism of action, pharmacokinetic drug
      interactions, and new drug discovery possibilities.
AB  - Despite recent advances in neurobiology and significant insight into the
      molecular dysfunction of epilepsy, about 25% of patients do not completely
      respond to current frontline therapeutic agents such as carbamazepine, phenytoin,
      valproic acid, ethosuximide, phenobarbital, and benzodiazepine. Recently, much
      effort has been made to discover new antiepileptic drugs effective in refractory
      seizures. Two major groups of drugs have emerged of which felbamate, gabapentin,
      lamotrigine, oxcarbazepine, and vigabatrin are among the most promising. The
      mechanism of action of the first group works by enhancing brain GABA activity
      (e.g. vigabatrin) while the second group inhibits excitatory amino acids (e.g.
      lamotrigine and felbamate). Oxcarbazepine acts in a similar manner to
      carbamazepine while gabapentin's mode of action is still unclear. The major
      clinical indications of these new antiepileptics are partial complex seizures.
      They exhibit limited drug interactions with few adverse effects. A rational
      approach to the drug discovery process is necessary in order to lead to novel
      effective therapy. Another line of research is the use of the structure-activity
      relationship to fine-tune the pharmacology of existing antiepileptics providing
      less adverse effects with the same or better efficacy. Clinical perspectives from
      the discovery of new drugs such as fosphenytoin and valproyl glycinamide look
      promising. Rapid development in molecular biologic techniques for the study of
      the neurophysiology of epilepsy and the neurotransmitters which are the target
      for the antiepileptic drugs may also provide better insight into the interactions
      of antiepileptics with either ion channels or brain receptors.

PMID- 9587045
TI  - Prescription of cardiovascular drugs in outpatient care: a survey of outpatients
      in a German university hospital.
AB  - AIMS: We evaluated ambulatory prescriptions by general practitioners for
      outpatients with cardiovascular (CV) disease referred to the cardiology
      outpatient clinic of the Frankfurt University Hospital in order to prove
      adherence to generally acknowledged therapy standards for treating CV disease.
      METHODS AND RESULTS: Appropriateness of current CV medication was assessed
      according to the following criteria: aspirin or anticoagulants obligatory after
      myocardial infarction (MI), unless contraindicated; beta-blockers should be
      prescribed after MI, unless contraindicated or not tolerated; ACE inhibitors
      should be given in left ventricular dysfunction (LVD) after MI, unless
      contraindicated; and hypertension should be adequately controlled. 346 patients
      (28-94 years) received a median of 3 CV drug prescriptions (range 0-7). 240
      patients had CAD, 142 patients previous MI, 121 patients had LVD (59 after MI),
      143 patients were hypertensive. Aspirin was used appropriately in 80% of all MI
      patients, 13% received oral anticoagulants due to atrial fibrillation. However,
      7% received no antithrombotic therapy. ACE inhibitors were administered in 65% of
      the MI patients with LVD. beta-blockers were used in 25% of the MI-patients. In
      the remaining patients, beta-blockers were contraindicated, not tolerated, and/or
      verapamil had been prescribed. However, in 14% of the patients beta-blockers were
      withheld without evident reason or alternative drug. In 41% of the hypertensive
      patients, blood pressure was not sufficiently controlled. CONCLUSION: A
      considerable number of ambulatory prescriptions for CV drugs are not in
      accordance with current therapeutic guidelines. The role of a cardiology
      outpatient clinic to detect the misuse or underuse of CV drugs is emphasised.

PMID- 9587047
TI  - Bioequivalence of Neoplanta capsule to Sandimmune Neoral, microemulsion
      formulations of cyclosporin A in human subjects.
AB  - A bioequivalence study of the Neoplanta capsule to the Sandimmune Neoral capsule,
      microemulsion formulations of cyclosporin A (CyA), was conducted. Twenty-four
      healthy Korean male subjects received each formulation at the CyA dose of 175 mg
      in a 2 x 2 crossover study. There was a 2-week washout period between the doses.
      Blood concentrations of CyA were monitored by a radioimmunoassay for over a
      period of 48 h after the administration. AUCinf (area under the blood
      concentration/time curve from time zero to infinity) was calculated by the linear
      log trapezoidal method. Cmax (maximum blood drug concentration) and Tmax (time to
      reach Cmax) were compiled from the blood concentration-time data. Analysis of
      variance was carried out using logarithmically transformed AUCinf and Cmax and
      untransformed Tmax. There were no significant differences between the
      formulations in these parameters. The point estimates and 90% confidence
      intervals for AUCinf (parametric), Cmax (parametric) and Tmax (nonparametric)
      were, in point estimate (90% confidence interval), 0.978 (0.937 approximately
      1.02), 0.954 (0.900 approximately 1.01) and 0.000 (-0.125 approximately 0.000),
      respectively, satisfying the bioequivalence criteria of the European Committee
      for Proprietary Medicinal Products and the U.S. Food and Drug Administration
      guidelines. Moreover, the modified Pitman-Morgan's adjusted F test and equal
      variance test (1-sided) indicated that the 2 formulations were comparable in
      intra- and interindividual variability in CyA bioavailability. Therefore, these
      results indicate that the 2 formulations of CyA are bioequivalent and, thus, may
      be prescribed interchangeably.

PMID- 9587046
TI  - Relationship between area under the concentration versus time curve of
      cyclosporin A, creatinine clearance, hematocrit value, and other clinical factors
      in Japanese renal transplant patients.
AB  - We evaluated the relationship between the area under the concentration versus
      time curve (AUC) of cyclosporin A (CsA) and several other clinical factors,
      because the clinical utility of AUC monitoring has been ambiguous. Fifty-four
      clinical time courses from 14 Japanese renal transplant patients during
      hospitalization, in the period from April 1990 to March 1997, were examined. In a
      bivariate regression analysis there was no correlation between the AUC and the
      daily dose of CsA (mg/kg/day) when the individual data or total series data were
      analyzed. In a chi-square test, the donor type of kidney (chi(2) = 25.254, df =
      1, p = 0.0000) and renal function-related episodes, i.e. acute tubular necrosis,
      hemodialysis, hypertension, nephrotoxicity, or rejection (chi(2) = 13.982, df =
      1, p = 0.0002) directly affected posttransplant renal function assessed by
      creatinine clearance, while episodes of hepatic function as assessed by the
      glutamate-pyruvate transaminase (GPT) activity level had no correlation with the
      posttransplant renal function evaluated according to creatinine clearance. In
      contrast, the renal function-related episodes significantly affected the AUC
      after renal transplantation (chi(2) = 4.934, df = 1, p = 0.0263), while hepatic
      function assessed by GPT did not. In a multivariate analysis, the creatinine
      clearance and obesity had significant positive correlations with the AUC, whereas
      the hematocrit had a significant negative correlation with the AUC. From these
      observations, we concluded that the dosage adjustment of CsA cannot be performed
      using the linear relationship between the daily oral dose and the AUC, and that
      renal function, obesity, and the CsA blood distribution properties affect the CsA
      pharmacokinetics after renal transplantation. Posttransplant renal function as
      well as obesity and CsA blood distribution properties are important factors to be
      considered when therapeutic monitoring is performed.

PMID- 9587048
TI  - Comparative bioavailability of various thiamine derivatives after oral
      administration.
AB  - In a multiple change-over study the bioequivalence of 3 thiamine preparations,
      used therapeutically as neurotropic agents for the treatment of polyneuropathies,
      was tested in a collective of 7 volunteers. After ingestion of a single dose of
      either 100 mg benfotiamin CS-benzoylthiamine-o-monophosphate), fursultiamin
      (thiamintetrahydrofurfuryldisulfide) or thiaminedisulfide, thiamine blood levels
      were analyzed for a 10-hour period. Thiamine was measured by HPLC after precolumn
      derivatization to thiochrome. The maximal thiamine concentration Cmax and its
      time (tmax) in plasma and hemolysate, the area under concentration time curve
      (AUC), and thiamine excretion in 24-hour urine were assessed as criteria of
      bioavailability. Additionally the erythrocytic transketolase activity (ETK) and
      alphaETK were determined as indicators of the cellular thiamine availability.
      After benfotiamin ingestion a more rapid and earlier increase of thiamine in
      plasma and hemolysate was observed in contrast to fursultiamin and the disulfide.
      All biokinetic data demonstrated a significantly improved thiamine
      bioavailability from benfotiamin compared with the other preparations. The lowest
      bioavailability was detected with thiamindisulfide. From our results it can be
      concluded that oral administration of benfotiamin is best suitable for
      therapeutical purposes owing to its excellent absorption characteristics.

PMID- 9587049
TI  - Comparative bioavailability of two tablet formulations of acyclovir in healthy
      volunteers.
AB  - This investigation was carried out to evaluate the bioavailability of a new
      tablet formulation of acyclovir (400 mg), Clovir, relative to reference product,
      Zovirax (400 mg) tablets. The 2 brands were found to be similar in weight
      variation, disintegration time, dissolution, and assay as stipulated by the
      USPXXIII, as well as by the manufacturer. The bioavailability was carried out on
      24 healthy male volunteers who received a single dose (400 mg) of the test (T)
      and the reference (R) products in the fasting state, in a randomized balanced 2
      way crossover design. After dosing, serial blood samples were collected for a
      period of 16 hours. Plasma harvested from blood was analyzed for acyclovir by a
      sensitive and validated high-performance liquid chromatographic assay. The
      maximum plasma concentration (Cmax), area under the plasma concentration-time
      curve up to the last measurable concentration (AUC0-t), and to infinity (AUC0
      infinity), and the absorption rate (Cmax/AUC0-infinity) were analyzed
      statistically under the assumption of a multiplicative model. The time to maximum
      concentration (Tmax) was analyzed assuming an additive model. The parametric
      confidence intervals (90%) of the mean values of the pharmacokinetic
      characteristics (AUC0-t, AUC0-infinity, Cmax, Cmax/AUC0-infinity) for T/R ratio
      were in each case, well within the bioequivalence acceptable range of 80-125%.
      The test formulation was found bioequivalent to the reference formulation by the
      Schuirmann's two 1-sided t tests and by Wilcoxon Mann Whitney two 1-sided tests
      procedure. Therefore, the 2 formulations were considered to be bioequivalent.

PMID- 9587050
TI  - Influence of biological variables upon pharmacokinetic parameters of
      intramuscular methotrexate in rheumatoid arthritis.
AB  - The pharmacokinetics of methotrexate were studied in 22 patients receiving 5-15
      mg per week in a single i.m. administration for rheumatoid arthritis. The data
      consisted of 3 plasma levels per patient, taken at 2, 6, and 12 hours after the
      administration. The concentration of methotrexate was determined by fluorescence
      polarization immunoassay. The pharmacokinetic parameters of a 2-compartment model
      were determined by Bayesian estimation using the population values of Bressolle
      et al. [1996]. The fitted parameters were: total plasma clearance of methotrexate
      (CL), first-order absorption constant (ka), volume of central compartment (V1),
      and transfer constants between the 2 compartments (k12 and k21). Additional
      parameters were derived from the fitted ones: maximal concentration (Cmax), time
      to maximum (tmax), volume of distribution at steady-state (Vss), and terminal
      half-life (t1/2). Twenty-one biological covariates were considered to explain the
      interpatient variability. The relationships between these covariates and the
      pharmacokinetic parameters were investigated by principal component analysis and
      multiple regression analysis. About 90% of the variability of CL were explained
      by 4 variables (sex, age, height and serum creatinine). About 50%-70% of the
      variability of the other pharmacokinetic parameters were explained by a set of
      covariates including age, height, creatinine, creatinine clearance, and dose. The
      effect of dose was noticed mainly on k12, Vss, and t1/2, thus suggesting that the
      transfer of the drug from plasma to tissues may be nonlinear. The possibility of
      predicting CL with a good precision would facilitate the computation of dosage
      regimens in these patients.

PMID- 9587051
TI  - Investigation on the bioequivalence of 2 oral preparations containing
      spironolactone and furosemide.
AB  - The bioequivalence of 2 formulations containing spironolactone and furosemide was
      determined. The test preparation was Spironolacton 50 plus Heumann tablets, a new
      generic spironolactone preparation, developed by Heumann Pharma GmbH, the
      reference preparation was Osyrol 50-Lasix capsules, Hoechst AG. The study was
      designed as a randomized 2-period, 2-sequence, crossover study. A daily dose of
      50 mg spironolactone and 20 mg furosemide was administered over 5 days to 24
      healthy volunteers in the fasting state. Plasma samples were assayed for
      spironolactone, its 2 active metabolites canrenone and 7alpha
      thiomethylspirolactone, and furosemide by HPLC. Statistical analysis was
      performed by ANOVA and by nonparametric methods. Because spironolactone was
      rapidly eliminated from plasma, its pharmacokinetics could only be evaluated with
      regard to maximum plasma levels. This parameter did slightly miss the criteria
      for bioequivalence. For canrenone and 7alpha-thiomethylspirolactone
      bioequivalence was given. For furosemide the test formulation was found to be
      equivalent concerning the extent of bioavailability. Bioequivalence with regard
      to maximum concentrations could not be shown. However, from the point of view of
      pharmacodynamics, this finding may not necessarily be of clinical relevance.

PMID- 9587052
TI  - In vitro condensation-sorting of enzyme proteins isolated from rat pancreatic
      acinar cells.
AB  - To study the process of granule formation in pancreatic acinar cells in more
      detail we have established an in vitro system in which the whole complement of
      enzyme proteins released from isolated zymogen granules is mixed with a tracer
      amount of the same biosynthetically labeled proteins and is incubated at
      conditions prevailing in either pre-Golgi (pH 7.5) or trans-Golgi (pH 5.9)
      compartments. Condensation of the proteins into dense cores is assayed and
      quantitated after centrifugation of the mixture at 13000g and separation of the
      proteins in both the supernatant and the pellet by 2D-gel electrophoresis. At pH
      7.5 about 1% of the total protein-bound radioactivity can be sedimented into the
      pellet and this increases 5-fold at pH 5.9 with similar sedimentation efficiency
      for individual enzyme proteins. The usual assumption that all aggregated proteins
      can be sedimented and thus only the pellet is representative for pH-dependent
      condensation has to be modified by the fine structural analysis of both the
      supernatant and pellet fraction at pH 7.5 and 5.9. Small particulate complexes
      form already in the supernatant at pH 7.5 which are not sedimented to a large
      extent into the pellet. At pH 5.9 aggregates of a homogeneous size of about 0.6
      to 0.8 microm formed in the supernatant while the pellet is composed of sheets
      and vesicles of membranes studded with dense core particles of about 20 to 30nm
      size. The pH-dependent protein condensation is a stepwise process starting with
      the formation of small dense core particles already at pH 8.0/7.5 which then
      progressively aggregate to form larger cores at pH 6.0/5.0. These aggregates can
      only be sedimented employing higher centrifugal forces. In the condensation
      process of pancreatic enzyme proteins calcium ions exert an effect only at pH
      7.5, leading to somewhat larger dense particles, while potassium ions are
      inhibitory both in protein condensation and in the binding of particles to
      membranes. The process of pH-dependent protein condensation is reversible and can
      be performed repetitively. The sedimentation of condensed proteins can be
      increased by the addition of isolated zymogen granule membranes. Thus the in
      vitro system allows the analysis of two related processes in granule formation:
      the condensation of secretory proteins into granule cores and their binding to
      the granule membrane.

PMID- 9587054
TI  - Anion exchanger 2 (AE2) binds to erythrocyte ankyrin and is colocalized with
      ankyrin along the basolateral plasma membrane of human gastric parietal cells.
AB  - The hydrochloric acid secreting parietal cells of the human stomach mucosa have
      been shown to express anion exchanger 2 (AE2). AE2 is restricted to the
      basolateral membrane domain and is responsible for the basolateral uptake of Cl-
      and release of HCO3-. It is unknown which mechanism is responsible for the
      basolateral positioning of AE2 in parietal cells. We raised the question whether
      AE2 might be immobilized at the cell surface by linkage via ankyrin to the
      spectrin/actin-based membrane cytoskeleton. In the present study we communicate
      two observations that support this hypothesis, namely that in parietal cells
      ankyrin is localized with AE2 along the basolateral cell surface and, secondly,
      that purified erythrocyte ankyrin binds to the in vitro-translated cytoplasmic
      domain of AE2. We conclude from these observations that AE2 in parietal cells
      might be linked via ankyrin to the basolateral membrane cytoskeleton and that
      this type of linkage might play a role in immobilizing AE2 in a non-random
      fashion along the basolateral membrane domain.

PMID- 9587053
TI  - Syntaxin-16, a putative Golgi t-SNARE.
AB  - Members of the syntaxin family of integral membrane proteins have recently been
      implicated as vesicle receptors on target membranes, coresponsible for the
      specificity of intracellular membrane traffic. So far, only a small number of
      different mammalian syntaxins have been identified. Here we report the cloning of
      three new human syntaxin cDNAs, presumably originating from alternative splicing
      of the same transcript. Syntaxin-16A and syntaxin-16B are identical, except that
      the latter contains an insertion of 21 amino acid residues. Syntaxin-16C is a
      truncated version of syntaxin-16A, lacking the C-terminal coiled-coil and
      hydrophobic regions characteristic for syntaxins. Database searches identified
      putative yeast, plant and nematode homologues of syntaxin-16, indicating that
      this protein is conserved through evolution, and syntaxin-16 belongs to a new
      subgroup of syntaxins. Epitope-tagged syntaxin-16A and syntaxin-16B were found to
      colocalize with the Golgi marker beta-COP, while syntaxin-16C was found in the
      cytosol. Syntaxin-16A associates posttranslationally with microsomes, and appears
      to be transported to the Golgi via the endoplasmic reticulum. The three syntaxin
      16 forms may have differential roles in intracellular trafficking.

PMID- 9587055
TI  - Changes in the nucleolar and coiled body compartments precede lamina and
      chromatin reorganization during fibre cell denucleation in the bovine lens.
AB  - Nuclear elimination accompanies differentiation in such specialized cell types
      such as erthyrocytes and lens fibre cells. It also accompanies apoptosis which
      has suggested that similar processes could operate in both. Denucleation occurs
      in the lens in order to reduce light scatter and this process is often disrupted
      in cataract. Using the adult bovine lens as a model system, nuclear changes
      accompanying denucleation are described with particular emphasis on the lamina,
      nucleolar and coiled body compartments in lens nuclei. Nuclear shape, chromatin
      reorganization and chromatin breakdown were also monitored to correlate the
      timing of events. Rearrangement of both A- and B-type nuclear lamins occurred in
      parallel with chromatin condensation and preceded changes in nuclear shape. The
      earliest changes detected in this study occurred in the coiled body and nucleolar
      compartments using coilin and fibrillarin antibodies respectively, suggesting
      that a shutdown in transcription is an early event in denucleation. Fibrillarin
      redistributed from an open floret pattern to several condensed spots which
      gradually decreased in intensity and eventually disappeared. Coilin, however, was
      localized in several microfoci prior to being reorganized into fewer larger foci.
      Prior to chromatin condensation, coilin redistributed to the nucleolar
      compartment and was absent from nuclei where chromatin had begun to condense.
      Such nuclei were positive by TUNEL staining. In contrast to the nucleus,
      mitochondrial degradation in lens fibre cells was a rapid process and involved a
      relatively sharp transition between positive and negative fibre cells for two
      mitochondrial specific markers, BAP 37 and prohibitin. A link between the changes
      in the nuclear lamina and chromatin with the initiation of mitochondrial
      fragmentation was also observed. Therefore, it is possible that the signal for
      the initiation of denucleation could originate from the mitochondria as proposed
      for apoptosis. Differences between apoptosis and lens fibre cell denucleation
      were noted and included the timescale of nuclear changes as well as the
      persistence of a nuclear remnant. These studies suggest that transcriptional
      shutdown precedes lamina reorganization and chromatin breakdown during lens fibre
      cell denucleation.

PMID- 9587056
TI  - Calpastatin-modulation of m-calpain activity is required for myoblast fusion.
AB  - Previous studies have demonstrated a role for m-calpain in myoblast fusion.
      Moreover, the presence, in differentiated cells, of a highly specific endogenous
      inhibitor of calpain, calpastatin, has led to the hypothesis that a regulation of
      or a protection against m-calpain activity by calpastatin could also occur during
      the earlier stages of muscle cell differentiation. In order to verify this
      hypothesis, we have investigated, in myoblast culture, the appearance of
      calpastatin-mRNA and its corresponding protein. Our results provide evidence that
      calpastatin is already present at the earlier stages of myoblast differentiation
      and that a significant decrease of the levels of calpastatin mRNA and its protein
      precedes myoblast fusion. In addition, the induction of an artificial decrease in
      calpastatin level, via an appropriate antisense oligodeoxyribonucleotide
      methodology, leads to earlier and faster myoblast fusion. Together with previous
      studies, these results indicate that m-calpain and calpastatin are functionally
      involved in myoblast fusion. Our findings also demonstrate that an acute
      "hyperactivity" of m-calpain resulting from the decrease of calpastatin synthesis
      is necessary during the early stages of this step of differentiation.

PMID- 9587057
TI  - Mirror expression of adrenoleukodystrophy and adrenoleukodystrophy related genes
      in mouse tissues and human cell lines.
AB  - The adrenoleukodystrophy and adrenoleukodystrophy related proteins belong to a
      new family of half ATP-binding cassette transporters which are localized within
      the peroxisomal membrane and whose functions are still unknown. They could
      possibly homo- or heterodimerize resulting in transporters with similar or
      distinct functions. The expression of adrenoleukodystrophy and
      adrenoleukodystrophy related genes was studied at the mRNA and protein levels in
      adult mouse tissues and several human cell lines. We found that
      adrenoleukodystrophy and adrenoleukodystrophy related genes have strikingly
      different expression in most mouse tissues and human cell lines analyzed,
      indicating that adrenoleukodystrophy and adrenoleukodystrophy related proteins do
      not function as obligatory partners but might rather fulfill similar metabolic
      functions in different tissues.

PMID- 9587058
TI  - Nonradioactive in situ hybridization for detection of hydrophobin mRNA in the
      phytopathogenic fungus Claviceps purpurea during infection of rye.
AB  - Hydrophobins are unique fungal extracellular proteins that produce amphipathic
      films at interfaces, mediate contact to hydrophobic surfaces and are known to be
      important in phytopathogenicity. In the pathogenic ascomycete Claviceps purpurea,
      causing ergot disease in grasses and cereals and ergotism in livestock, a gene
      encoding an extraordinary type of hydrophobin has been detected, which appeared
      to be induced during alkaloid synthesis in axenic culture of an ergot-alkaloid
      producing strain of Claviceps (V. Garre and P. Tudzynski, pers. communication;
      Arntz and Tudzynski, 1997, Curr. Genet. 31, 357-360). To elucidate presence and
      function of this hydrophobin during infection of rye, the nonradioactive in situ
      hybridization technique was successfully adapted to the fungal organism and
      optimized in the pathogenic interaction system. Semithin cryosections proved to
      be suitable for microscopical gene expression analysis using immune-mediated
      alkaline-phosphatase staining for detection of digoxigenin-labeled cRNA probes.
      Specific hybridization of the prepared antisense riboprobe to hydrophobin mRNA
      was confirmed in nonradioactive Northern blots. While permeabilization by
      proteinase K had only a minor effect, the inclusion of detergent into the
      hybridization solutions enhanced specific RNA-RNA hybridization under maximum
      stringency. Hydrophobin mRNA was found in fungal cells, growing in axenic
      culture. In the disease cycle, hydrophobin transcripts were localized in
      abundance during vegetative fructification in conidiophores that actively
      produced conidia. No signals were observed in sclerotial hyphae during formation
      of the alkaloid-containing ergots, although they fluoresced intensely during
      total RNA detection using acridine orange. Notably, in situ hybridization
      experiments resulted in specific signals during early infection and colonization
      phases in the external mycelia and in hyphae penetrating the host epidermal
      layer. The presumed role of the hydrophobin gene product in ergot pathogenicity
      is discussed with respect to the described spatio-temporal distribution of the
      hydrophobin transcripts.

PMID- 9587059
TI  - Epidermal differentiation and basement membrane formation by HaCaT cells in
      surface transplants.
AB  - The immortal human keratinocyte line HaCaT has been employed in many studies as
      paradigm for epidermal keratinocytes. In order to demonstrate its potential to
      form stable epidermal structures in response to connective tissue, this was
      challenged in surface transplants on nude mice, where normal keratinocytes
      rebuild a typical epidermis within two weeks. During the initial regeneration
      phase (day 1-4) multilayered but poorly organized epithelia formed with
      proliferating cells in all layers in analogy to normal keratinocytes. Similarly,
      with tissue consolidation (around day 7) proliferation was reduced and restricted
      to cells in basal position marked by keratin K14 and beta1-integrin
      immunostaining. The strong suprabasal reaction for K1 and K10, the appearance of
      the late markers K2e, filaggrin and loricrin as well as the polarized
      distribution of alpha2beta1 and alpha3beta1 indicated advancing tissue
      normalization (day 14). Keratinization further improved at around three weeks
      switching from the initial parakeratotic to the regular orthokeratotic type which
      was prominent at six weeks. Accordingly, most ultrastructural features typical
      for epidermis or normal keratinocyte grafts were detectable including a complete
      basement membrane (BM) with regular attachment structures. Matrix- and BM
      components appeared sequentially with marked linear deposition of laminin-5 (day
      4) followed by accumulation of collagen-IV and 'classical' BM-laminin between one
      and two weeks. With the general codistribution of integrin alpha6beta4 and BM
      molecules (day 14) collagen-VII lining of BM became prominent, while epithelium
      and host connective tissue were still separated by the collagen matrix. In
      accordance with the delayed orthokeratinization, wound-matrix molecules
      (fibronectin, tenascin) persisted longer than in normal keratinocyte transplants.
      Finally, grafts of long-term passaged (no. 310) cells demonstrated a remarkable
      stability in the expression of epidermal markers. Thus, the immortalized HaCaT
      cells reveal a generally high competence to realize an epidermal phenotype in a
      natural environment and appear therefore qualified for in vitro studies on
      structural and regulatory aspects of keratinocyte physiology and pathology.

PMID- 9587060
TI  - IL-4 addition during differentiation of CD34 progenitors delays maturation of
      dendritic cells while promoting their survival.
AB  - Dendritic cells (DC) are the most effective cells for antigen presentation in
      primary immune responses. Human cord blood CD34+ progenitors cultured in the
      presence of GM-CSF and TNF alpha generate a heterogeneous population of DC
      including Langerhans-like DC (LLDC) and monocytes. We describe here that IL-4
      exerts different effecs in such culture according to the cells considered. Thus,
      IL-4 favors DC components at the expense of monocytic development, and permits
      long-time persistence of DC which can be maintained up to one month in culture.
      These results show an IL-4-dependent inhibition of proliferation and emergence of
      CD14+ cells. Notably, however, IL-4 also acts on the DC precursors. Thus, IL-4
      enhances survival and delays maturation of LLDC from CD1a+ CD14- precursors. In
      addition, IL-4 also favors orientation of CD14+ CD1a- DC/monocyte precursors
      towards dermal-type CD1a+ DC. DC recovered from IL-4 treated cultures display
      reduced allostimulatory capacity, but this function is restored upon IL-4
      weaning. Finally, a short (48h) IL-4 pulse is sufficient to favor DC development.
      The present study demonstrates that IL-4 positively regulates DC development at
      several levels on distinct precursor cells.

PMID- 9587061
TI  - The Congress of Molecular Medicine: a truly modern meeting.

PMID- 9587062
TI  - Aging beats the alternative.

PMID- 9587063
TI  - Clinical and molecular aspects of nephropathic cystinosis.
AB  - Nephropathic cystinosis, an autosomal recessively inherited lysosomal storage
      disease, results from impaired transport of the disulfide amino acid cystine out
      of cellular lysosomes. The consequent accumulation and crystallization of cystine
      destroys tissues, causing growth retardation in infancy, renal failure at 10
      years of age, and a variety of other complications. Early oral therapy with the
      cystine-depleting agent cysteamine prevents renal deterioration and enhances
      growth. Although the lysosomal cystine carrier has been extensively studied, its
      molecular structure remains unknown. The lysosomal cystine transporter gene has
      been mapped by linkage analysis to human chromosome 17p between polymorphic
      microsatellite markers D17S1583 and D17S1584. Pertinent recombination events and
      homozygosity by descent has verified that the cystinosis gene lies in the 3.6 cM
      genetic interval between these two markers. The cystinosis region has been
      substantially reduced in size by the observation of recombination events in
      cystinosis patients between markers D17S1828 and D17S2167. According to radiation
      hybrid analysis, these two markers are separated by 10.2 cR8000 (centirad using
      8000 rad radiation hybrids). Estimates of the physical size of this interval
      range from 187 to 510 kb. Four yeast artificial chromosomes have been identified
      which form a contig covering the original cystinosis region. Two P1 clones
      together may span the new, smaller interval, meaning that the cystinosis gene
      would lie on one of them. Current efforts are being directed toward using these
      P1 clones to isolate candidate cDNAs by a variety of methods. The ultimate
      cloning of the cystinosis gene will reveal how functional lysosomal porters are
      synthesized, targeted, processed, and integrated into the lysosomal membrane.

PMID- 9587064
TI  - Autosomal recessive polycystic kidney disease.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited
      disorder which usually becomes clinically manifest in early childhood, although
      the spectrum of ARPKD is much more variable than generally known. Presentation of
      ARPKD at later ages and survival into adulthood have been observed in many cases.
      The responsible gene has been mapped to chromosome 6p. Thus there is no evidence
      of genetic heterogeneity. The most important indication for DNA diagnosis is the
      prenatal diagnosis in families with at least one affected child. The critical
      region has been narrowed with the use of recombinant families of about 4 cM.
      Several possible candidate genes have been excluded.

PMID- 9587065
TI  - Familial juvenile nephronophthisis.
AB  - Familial juvenile nephronophthisis (NPH) is an autosomal recessive interstitial
      nephritis leading to terminal renal failure around puberty. Associations with
      extrarenal symptoms have been reported, mainly with Leber amaurosis (termed
      Senior-Loken syndrome). By means of linkage analysis a gene NPH1 for the purely
      renal form of NPH has been localized to chromosome 2. Genetic heterogeneity has
      been shown between NPH and Senior-Loken syndrome and also within the group of
      isolated NPH cases. Further characterization of the NPH1 region led to the
      isolation of large homozygous deletions in approximately 70% of patients with
      NPH. The detection of these deletions by PCR represents a simple noninvasive
      method for precise diagnosis in the majority of patients suspected of having NPH.

PMID- 9587066
TI  - The molecular genetic approach to "Bartter's syndrome".
AB  - The term "Bartter's syndrome" comprises a set of autosomal recessively inherited
      renal tubular disorders characterized by hypokalemia, metabolic alkalosis,
      hyperreninism, and hyperaldosteronism but normal blood pressure. Additional
      clinical and biochemical features led to a classification into phenotypically
      different tubulopathies: Gitelman's syndrome, hyperprostaglandin E syndrome
      (antenatal Bartter's syndrome), and classic Bartter's syndrome. Gitelman's
      syndrome results from mutations in the SLC12A3 gene encoding the human thiazide
      sensitive sodium chloride cotransporter, leading to impaired reabsorption of
      sodium chloride in the distal convoluted tubule. Genetic heterogeneity of
      hyperprostaglandin E syndrome has been demonstrated by identification of
      mutations in the SLC12A1 gene as well as in the KCNJ1 gene. Mutations in SLC12A1
      coding for the bumetanide-sensitive sodium potassium 2 chloride cotransporter
      (NKCC2) cause defective reabsorption of sodium chloride in the thick ascending
      limb of Henle's loop. Mutations in KCNJ1 leading to loss of function of the
      potassium channel ROMK disrupt potassium recycling back to the tubule lumen and
      inhibit thereby the NKCC2 activity. A third gene for hyperprostaglandin E
      syndrome has been mapped to the short arm of chromosome 1, and it remains to be
      evaluated whether other genes are involved in the pathogenesis of this disease.
      Classic Bartter's syndrome has been demonstrated to result from defective
      chloride transport across the basolateral membrane in the distal nephron due to
      mutations in the chloride channel gene CLCNKB. This article reviews the molecular
      genetic approach that has led to identification of genetic defects underlying the
      different hypokalemic tubulopathies.

PMID- 9587067
TI  - The molecular basis of nephrogenic diabetes insipidus.
AB  - Nephrogenic diabetes insipidus (NDI) is characterized by resistance of the kidney
      to the action of arginine-vasopressin (AVP); it may be due to genetic or acquired
      causes. Recent advances in molecular genetics have allowed the identification of
      the genes involved in congenital NDI. While inactivating mutations of the
      vasopressin V2 receptor are responsible for X-linked NDI, autosomal recessive NDI
      is caused by inactivating mutations of the vasopressin-regulated water channel
      aquaporin-2 (AQP-2). About 70 different mutations of the V2 receptor have been
      reported, most of them missense mutations. The functionally characterized mutants
      show a loss of function due to defects in their synthesis, processing,
      intracellular transport, AVP binding, or interaction with the G protein/adenylyl
      cyclase system. Thirteen different mutations of the AQP-2 gene have been
      reported. Functional studies of three AQP-2 mutations reveal impaired cellular
      routing as the main defect. The great number of different mutations with various
      functional defects hinders the development of a specific therapy. Gene therapy
      may, however, eventually become applicable to the congenital forms of NDI. At
      present all gene-therapeutic approaches lack safety and efficiency, which is of
      particular relevance in a disease that is treatable by an adequate water intake.
      The progress with regard to the molecular basis of antidiuresis contributes to
      the understanding of acquired forms of NDI on a molecular level. Recent data show
      that lithium dramatically reduces the expression of AQP-2. Likewise, hypokalemia
      reduces the expression of this water channel. The exact mechanisms leading to
      this reduced expression of AQP-2 remain to be determined.

PMID- 9587068
TI  - Processing of precursors of gastroenteropancreatic hormones: diagnostic
      significance.
AB  - The structures and posttranslational maturation patterns of pancreatic and
      gastrointestinal prohormones are reviewed with emphasis on both general and tumor
      specific prohormone processing patterns. Since prohormone processing in
      neuroendocrine tumors is often attenuated, conventional assays that measure only
      the phenotypic endpoint of hormone gene expression (i.e., the bioactive hormone)
      do not quantitate tumor activity accurately. In contrast, measurements that also
      include prohormones and processing intermediates provide more accurate data on
      hormone synthesis in gastroenteropancreatic neuroendocrine tumors. To meet such
      demands we have developed an analytical principle (processing-independent
      analysis) which quantitates the entire translation product irrespective of the
      degree of processing. Prospective evaluation in routine diagnostics has shown
      that processing-independent analysis contributes to ensuring correct diagnosis
      when gastroenteropancreatic tumors are still small and tumor symptoms
      uncharacteristic (borderline cases).

PMID- 9587069
TI  - Increased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from
      centenarians.
AB  - Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins
      which is catalyzed by poly(ADP-ribose) polymerase and represents an immediate
      response of eukaryotic cells to oxidative and other types of DNA damage.
      Previously a strong correlation had been detected between maximal poly(ADP
      ribose) polymerase activity in permeabilized mononuclear leukocytes of various
      mammalian species and species-specific life span. To study a possible relation
      between longevity and poly(ADP-ribosyl)ation in humans we measured maximal
      oligonucleotide-stimulated poly(ADP-ribose) polymerase activity in permeabilized,
      Epstein-Barr virus transformed lymphoblastoid cell lines from a French population
      of 49 centenarians and 51 controls aged 20-70 years. Maximal enzyme activity was
      significantly higher in centenarians than in controls [median of controls: 9035
      cpm/10(6) cells (lower quartile: 6156; upper quartile: 11,410); median of
      centenarians: 10,380 cpm/10(6) cells (lower quartile: 7994; upper quartile:
      12,991); P=0.031 by Mann-Whitney U test]. In a subset of 16 controls and 24
      centenarians, cellular poly(ADP-ribose) polymerase content was determined by
      quantitative western blotting, thus allowing the calculation of specific enzyme
      activity. The latter was significantly higher in centenarians (P=0.006), the
      median value for centenarians being about 1.6-fold that of controls. Specific
      poly(ADP-ribose) polymerase activity was a more powerful parameter for
      differentiating between centenarians and controls than enzyme activity relative
      to cell number. In addition, in a genetic association study we analyzed 437 DNA
      samples (239 centenarians and 198 controls) by PCR amplification of a polymorphic
      dinucleotide repeat located in the promoter region of the poly(ADP-ribose)
      polymerase gene in an attempt to detect an association between this polymorphic
      marker and variability of enzyme activity or human longevity. However, this
      genetic analysis revealed no significant enrichment of any of the alleles or
      genotypes identified among centenarians or controls, but its power was limited by
      the relatively weak heterozygosity of this polymorphic marker in our population
      (51%). Viewed together with previous results on poly(ADP-ribose) polymerase
      activity in various mammalian species, the present data provide further evidence
      for the notion that longevity is associated with a high poly(ADP-ribosyl)ation
      capacity.

PMID- 9587070
TI  - Expression of type III hyperlipoproteinemia in patients homozygous for
      apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial
      hyperinsulinemia.
AB  - Type III hyperlipoproteinemia (HLP) is a multifactorial disorder associated with
      homozygosity for the apolipoprotein (apo) E-2 allele. Factors which may promote
      the development of HLP include lipoprotein lipase (LPL) and hyperinsulinemia.
      These factors were investigated in eight patients with type III HLP and in nine
      normolipidemic controls. In vitro the interaction of apoE with LPL was analyzed
      in cell binding assays. All type III HLP patients showed delayed triglyceride
      (TG) clearance and remnant lipoprotein accumulation in an oral fat tolerance
      test. Normolipidemic apoE-2/2 controls revealed normal TG clearance comparable to
      apoE3/3 controls. HLP patients showed lower LPL activity and mass than controls.
      Analysis of the LPL gene revealed an Asn 291-->Ser mutation in three patients and
      a -93 T-G substitution combined with an Asp 9-->Asn mutation in one control
      subject. In addition to LPL abnormalities, postprandial hyperinsulinemia was
      observed in five out of eight patients. In vitro LPL compensated the defective
      function of apoE-2 in mediating remnant lipoprotein binding to cells. In summary,
      seven out of eight patients with type III HLP showed LPL abnormalities and/or
      postprandial hyperinsulinemia. Together with the in vitro data these findings
      support a coordinate effect of apoE and LPL for the manifestation of type III
      HLP. Hyperinsulinemia appears to be an additional factor important for disease
      expression.

PMID- 9587071
TI  - 27-bp deletion in the ret proto-oncogene as a somatic mutation associated with
      medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma (MTC) occurs as a sporadic tumor or in connection
      with the inherited cancer syndromes of multiple endocrine neoplasia (MEN) types
      2A and 2B and familial MTC. Missense RET proto-oncogene mutations of one of
      cysteine codons in exons 10 and 11 are found in the majority of families with MEN
      2A and or familial MTC. In MEN 2B, mutations at codon 918, exon 16, have been
      identified in most of the affected individuals. In a significant amount of
      sporadic MTC somatic codon 918 mutations appear. In addition to these, a 6-bp
      deletion including codon 630 and a 24-bp deletion including codon 634 combined
      with a 6-bp insertion have been observed. We report on a 27-bp deletion in exon
      10 as a somatic mutation associated with a sporadic medullary thyroid carcinoma.

PMID- 9587072
TI  - Track structure in radiation biology: theory and applications.
AB  - PURPOSE: A brief review is presented of the basic concepts in track structure and
      the relative merit of various theoretical approaches adopted in Monte-Carlo track
      structure codes are examined. In the second part of the paper, a formal cluster
      analysis is introduced to calculate cluster-distance distributions. METHOD: Total
      experimental ionization cross-sections were least-square fitted and compared with
      the calculation by various theoretical methods. Monte-Carlo track-structure code
      Kurbuc was used to examine and compare the spectrum of the secondary electrons
      generated by using functions given by Born-Bethe, Jain-Khare, Gryzinsky, Kim
      Rudd, Mott and Vriens' theories. The cluster analysis in track structure was
      carried out using the k-means method and Hartigan algorithm. RESULTS: Data are
      presented on experimental and calculated total ionization cross-sections: inverse
      mean free path (IMFP) as a function of electron energy used in Monte-Carlo track
      structure codes; the spectrum of secondary electrons generated by different
      functions for 500 eV primary electrons; cluster analysis for 4 MeV and 20 MeV
      alpha-particles in terms of the frequency of total cluster energy to the root
      mean-square (rms) radius of the cluster and differential distance distributions
      for a pair of clusters; and finally relative frequency distribution for energy
      deposited in DNA, single-strand break and double-strand breaks for 10MeV/u
      protons, alpha-particles and carbon ions. CONCLUSIONS: There are a number of
      Monte-Carlo track-structure codes that have been developed independently and the
      bench-marking presented in this paper allows a better choice of the theoretical
      method adopted in a track-structure code to be made. A systematic bench-marking
      of cross-sections and spectra of the secondary electrons shows differences
      between the codes at atomic level, but such differences are not significant in
      biophysical modelling at the macromolecular level. Clustered-damage evaluation
      shows: that a substantial proportion of dose ( 30%) is deposited by low-energy
      electrons; the majority of DNA damage lesions are of simple type; the complexity
      of damage increases with increased LET, while the total yield of strand breaks
      remains constant; and at high LET values nearly 70% of all double-strand breaks
      are of complex type.

PMID- 9587073
TI  - What has the cloning of the ATM gene told us about ataxia telangiectasia?
AB  - PURPOSE: To review what the cloning of the ATM gene has told us about ataxia
      telangiectasia (A-T). CONCLUSIONS: Perhaps the most interesting and potentially
      useful finding following the cloning of the gene has been the discovery of
      homologies with various previously known PIK related kinases. There is also a
      very wide range of mutations associated with A-T and it is clear that some ATM
      mutations can lessen the severity of both the clinical and cellular features of
      the disorder. The function(s) of ATM remain an enigma. There are several
      indications of its involvement in protecting the cell from the effects of
      ionizing radiation and radiomimetic agents, although the pathways that involve
      p53 and c-Abl are far from clear. Expression of AIM in tissue culture cells can
      reverse the cellular features of A-T, particularly the increased level of
      radiosensitivity. The localization of ATM on meiotic chromosomes and its
      speculated role in meiotic recombination is an important finding. Finally,
      cloning the ATM gene has allowed the development of mouse models, which are
      providing information about A-T and will be crucial for testing future treatments
      for the disorder.

PMID- 9587074
TI  - The multi-step nature of carcinogenesis and the implications for risk analysis.
AB  - PURPOSE: For the purposes of constructing biologically realistic models of
      radiation cancer risk it is necessary to have detailed knowledge of the post
      irradiation mechanisms involved. METHODS: This brief review considers selected
      aspects of DNA damage response, tumour initiation/development, together with
      attendant factors and provides comment on the implications for cancer risk
      estimation and some of the uncertainties that remain. CONCLUSIONS: It is judged
      from studies with animal models that, in the main, radiation tumorigenesis
      proceeds in a conventional multi-step fashion following radiation-induced
      specific gene losses from single-target stem cells.

PMID- 9587075
TI  - Recent epidemiological studies on ionizing radiation and childhood cancer in
      Germany.
AB  - PURPOSE: The results from recent epidemiological studies based on the German
      Childhood Cancer Registry are summarized. MATERIALS AND METHODS: An oecological
      study covers 16 years' incidence of childhood malignancies in areas surrounding
      nuclear facilities and in matched control regions. Two population-based case
      control studies explore potential risk factors of childhood leukaemia in the
      state of Lower Saxony (1988 93) and in all western states of Germany (1992-94).
      RESULTS: There was no increased incidence of childhood leukaemia and other
      malignancies in the vicinity of nuclear installations. X-ray examinations during
      pregnancy and in early childhood were not associated with an increased risk of
      childhood leukaemia. There were no data to support Gardner's hypothesis of an
      increased risk due to paternal pre-conception exposure to ionizing radiation.
      Following the Chernobyl accident, the reported incidence of neuroblastoma and
      infant leukaemia was increased. The increase cannot be explained by exposures due
      to the accident. CONCLUSIONS: Although the carcinogenic effect of ionizing
      radiation is well known, the recent population-based epidemiological studies show
      that under current conditions exposure to ionizing radiation in Germany does not
      constitute risks of childhood malignancies that are relevant to public health.

PMID- 9587076
TI  - Outstanding issues in radiation dose-fractionation studies.

PMID- 9587077
TI  - Altered fractionation in the management of head and neck cancer.
AB  - Progress in radiation science led to the development of two classes of
      biologically sound fractionation schedules for the treatment of head and neck
      cancers. These altered fractionation regimens are referred to as
      hyperfractionation and accelerated fractionation schedules. Hyperfractionation
      exploits the difference in fractionation sensitivity between tumours and tissues
      manifesting late morbidity and only minor variations exist among regimens tested.
      In contrast, accelerated fractionation attempts to reduce tumour proliferation as
      a major cause of radiotherapy failure. Although there are major permutations, the
      existing schedules can conceptually be grouped into two categories, namely pure
      accelerated fractionation and hybrid accelerated regimens, depending on whether
      there are concurrent changes in other fractionation parameters. The results of
      completed phase III clinical trials addressing different types of altered
      fractionation schedules in head and neck carcinomas are summarized and examined
      in this review paper. The data from trials on hyperfractionation regimens
      applying 10-15% total dose increment consistently revealed a 10-15% improvement
      in the local control rate of a subset of intermediate-stage carcinomas without
      increasing the incidence of late complications. The available data on accelerated
      fractionation regimens already showed that tumour clonogen proliferation is a
      major cause of radiation failure. However, completed studies revealed that a 1
      1.5 week treatment acceleration without total-dose reduction, achieved by
      administering 2 Gy fractions six times per week or concomitant boost schedule,
      yielded a 15% higher tumour control rate without increasing late toxicity.
      Shortening the overall time to below 2 weeks with an associated total-dose
      reduction did not seem to improve the tumour control rate but might decrease some
      late normal-tissue injury. A weekly dose accumulation rate of > or =14 Gy or
      delivery of three fractions of 1.6 Gy per day, with a 6 h interval, without total
      dose reduction was found to increase morbidity significantly. Further treatment
      refinements are being pursued based on these findings.

PMID- 9587078
TI  - Molecular and cellular basis of radiation fibrosis.
AB  - PURPOSE: Recent data from the literature and the experimental work of the authors
      clearly indicate that TGF-beta1 is a key modulator of cellular events, for
      example, induction of terminal differentiation, resulting in radiation-induced
      fibrosis. Therefore, the present study analysed which cellular processes induced
      by exogenously added TGF-beta could be responsible for the induction, development
      and manifestation of the fibrotic phenotype in culture. MATERIALS AND METHODS:
      Rat lung fibroblast cultures (passage 1) were used. As a function of treatment
      with TGF-beta and/or anti-TGF-beta-antibody, the clonogenic activity and
      differentiation pattern were analysed by colony-formation assays. RESULTS: It
      could be demonstrated that treatment of rat lung progenitor fibroblasts with TGF
      beta1 resulted in a pronounced shift in the differentiation pattern, i.e.
      induction of post-mitotic fibrocytes. This TGF-beta1-dependent terminal
      differentiation could be abolished by simultaneous treatment with a neutralizing
      antibody directed against TGF-beta1. CONCLUSIONS: The data presented indicate
      that TGF-beta1 is one major candidate mediating the accelerated terminal
      differentiation of progenitor fibroblasts to post-mitotic functional fibrocytes,
      which results in the fibrotic phenotype of this cell system.

PMID- 9587079
TI  - The intrinsic radiosensitivity of normal and tumour cells.
AB  - PURPOSE: To examine whether in vitro measurements of normal and tumour cell
      radiosensitivity can be used as prognostic factors in clinical oncology.
      MATERIALS AND METHODS: Stage I-III cervix carcinoma patients were treated with
      radical radiotherapy with a minimum of 3 years' follow-up. Lymphocyte and tumour
      radiosensitivities were assayed using, respectively, a limiting dilution and soft
      agar clonogenic assay to obtain surviving fraction at 2 Gy (SF2). The results
      were related, in an actuarial analysis, to late morbidity assessed using the
      Franco Italian glossary. RESULTS: Patients with radiosensitive lymphocytes had a
      significantly increased risk of developing late complications (n = 93, p =
      0.002). Increasing tumour radiosensitivity was associated with an increased risk
      of morbidity (n= 113, p=0.032). A significant correlation was found between
      fibroblast and tumour cell radiosensitivity (r=0.57, p=0.03), but a weak inverse
      association was found between lymphocyte and tumour cell radiosensitivity (r= 
      0.32, p=0.03). Patients with radiosensitive lymphocytes and tumour cells had
      higher levels of late complications than those whose cells were radioresistant.
      CONCLUSION: The work described highlights the importance of cellular
      radiosensitivity as a parameter determining the clinical response to
      radiotherapy.

PMID- 9587080
TI  - Angiotensin II receptor antagonists in the treatment and prevention of radiation
      nephropathy.
AB  - PURPOSE: Angiotensin-converting enzyme (ACE) inhibitors are effective in the
      prophylaxis of radiation-induced renal and lung injury. Studies were designed to
      determine whether blocking the angiotensin II (AII) receptor, rather than
      blocking AII synthesis with ACE inhibitors, would also be effective. MATERIALS
      AND METHODS: Rats received total body irradiation (TBI) followed by bone marrow
      transplantation (BMT), and were randomized to: an ACE inhibitor (captopril); an
      AII type 1 (AT1) receptor antagonist (L-158,809); or no treatment. Drug therapy
      began 9 days prior to BMT and continued for the duration of the study. RESULTS:
      Analysis of renal function, histopathology and animal survival showed that the
      AII blocker was more effective than the ACE inhibitor in the prophylaxis of BMT
      nephropathy. Further studies have shown that the AII blocker is as effective as
      captopril in the treatment of established radiation nephropathy, and that the AII
      blocker is at least as effective as captopril in the prophylaxis of lung injury
      induced by chemo-radiation therapy. CONCLUSIONS: These studies indicate that
      blockage of the AT1 receptor by itself is sufficient for the treatment of
      radiation-induced renal and lung injury, hence the renin-angiotensin system is
      fundamentally involved in the pathogenesis of these injuries. These studies
      provide further evidence that there is more to late radiation injuries than
      delayed mitotic cell death.

PMID- 9587081
TI  - Prenatal irradiation: a major concern for the developing brain.
AB  - Irradiation of the mammalian foetus produces a broad spectrum of congenital
      abnormalities, growth retardations, developmental delays, and functional
      deficits, depending upon the dose and the specific gestational phase of
      irradiation. The developing brain is particularly susceptible to production of
      deleterious effects, with decreased brain size, behavioural alterations, and
      mental retardation having been documented. Supplementing the limited human data,
      rodent models have been extensively used to investigate the specific processes by
      which relatively low doses, with correspondingly minor cellular damage to the
      developing neocortex, can produce dramatic postnatal consequences in brain
      structure and function. The effects of a variety of physical (dose, linear energy
      transfer, dose rate, fractionation) and biological (species, strain, gestational
      age, time course post-irradiation) parameters have been examined in an attempt to
      provide much needed information on such critical aspects as dose response,
      threshold doses for effect, and extrapolation to human risk estimates. Various
      acute cellular responses (e.g. appearance of pyknotic cells and macrophages)
      observed in the developing neocortex 0-24 h after in utero irradiation can be
      associated with postnatal effects. Moreover, it is possible to correlate thinning
      of specific layers of the cerebral cortex with specific behavioural aberrations,
      allowing prediction of brain structural changes from functional alterations, and
      vice versa. Thus, it is possible to speculate as to the mechanisms and targets
      for extremely sensitive, radiation-induced cellular damage in the developing
      foetal brain, that will interfere with the orderly and precisely programmed
      development of the mammalian brain, leading finally to postnatal expression as
      delays in growth and development, perturbations in behaviour, and alterations in
      brain structure.

PMID- 9587082
TI  - Radiation accidents: lessons learnt for future radiological protection.
AB  - PURPOSE: To review major radiation accidents that have occurred over a 50 year
      period. To identify common factors, since feedback may prevent recurrence.
      METHODS: Accidents are classified according to the difficulties involved in their
      management and to the delay between their occurrence and their recognition.
      RESULTS: The rate of severe accidents increases with time, especially those
      involving the public, and accidents are not always immediately recognized. The
      real number of serious unrecognized accidents is unknown. Human factors, such as
      lack of elementary safety rules and inadequate training, play a major role in
      most of the accidents occurring in industry and in the medical field.
      CONCLUSIONS: Common sense could have prevented many severe accidents that
      resulted in deaths and serious injuries. Delay in the identification of accidents
      results in severe consequences. Pre-planning is essential and may minimize the
      severity and the deterioration of the situation. Research efforts in the field of
      medical handling of severely radiation-injured victims should be maintained.

PMID- 9587083
TI  - Bacq and Alexander Award lecture--chemical radioprotection: past, present, and
      future prospects.
AB  - PURPOSE: To review and evaluate the development of effective radiation
      protectors. OUTLINE: Sulphydryl radioprotectors are the best radioprotectors
      known today. Their use encounters two great difficulties: their toxicity and the
      short period during which they are active. The biological response modifiers
      (BRM), developed mainly in the 1990s, demonstrated some protective effects. They
      can also modulate radiation injury when given after irradiation. In parallel with
      the use of single radioprotectors, observations have been made in mice using
      combined treatments with BRM and other radioprotectors. Low-to-moderate doses of
      several radioprotective agents acting via different mechanisms markedly improved
      the degree of protection in rodents while maintaining toxicity within acceptable
      limits, but applications in man remain doubtful. CONCLUSIONS: No radioprotective
      drug available today has all the requisite qualities to be an ideal
      radioprotector. Although combinations of radioprotective drugs acting via
      different mechanisms markedly improve the degree of protection and keep toxicity
      to acceptable levels in small rodents, attempts to use such treatments in large
      mammals have been less successful. It is thus questionable whether chemical
      protection has any prospects for the future.

PMID- 9587085
TI  - Patient compliance with peak flow monitoring in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: The factors affecting patient compliance with peak flow monitoring in
      advanced chronic obstructive pulmonary disease (COPD) were examined using a
      prospective, blinded study. METHODS: Twenty-eight male veterans were instructed
      in the use of an electronic, hand-held peak flow meter and the modified Medical
      Research Council dyspnea scale. They then entered a 6-month monitoring phase in
      which they recorded a dyspnea score once daily and peak expiratory flow rates
      twice daily, before and after bronchodilator use. The meter displays were
      disabled so that the patients were blinded to their values. Medical care was
      provided in the customary manner. Compliance was defined as the ratio of recorded
      values to all values specified by the protocol, exclusive of those missing due to
      circumstances beyond the patient's control. RESULTS: Of 40 patients who met the
      entry criteria for this study, 8 refused to participate and 4 could not master
      the technique. The remaining 28 patients were enrolled. Overall, 25 (63% of those
      eligible) adhered to the protocol until its conclusion or until they became
      unable to comply because of medical or social problems. Compliance was 89.8+/
      15.0%. Of those followed for longer than 150 days, linear regression showed that
      only one patient had a decline in compliance over time (r=0.84, P=0.04).
      Compliance was lower in the afternoons (P < 0.001) and on days with higher
      dyspnea scores (P < 0.001). No other clinical factors had an effect on patient
      measurements. CONCLUSIONS: A substantial proportion of patients with advanced
      COPD can be trained in the technique of peak flow monitoring. Compliance is high
      if patients are enrolled in a long-term, structured program of supervision and
      periodic retraining.

PMID- 9587084
TI  - Distribution and observed associations of orthostatic blood pressure changes in
      elderly general medicine outpatients.
AB  - Factors associated with orthostatic blood pressure change in elderly outpatients
      were determined by surveying 398 medical clinical outpatients aged 65 years and
      older. Blood pressure was measured with random-zero sphygmomanometers after
      patients were 5 minutes in a supine and 5 minutes in a standing position.
      Orthostatic blood pressure changes were at normally distributed levels with
      systolic and diastolic pressures dropping an average of 4 mm Hg (standard
      deviation [SD]=15 mm Hg) and 2 mm Hg (SD=11 mm Hg), respectively. Orthostatic
      blood pressure changes were unassociated with age, race, sex, body mass, time
      since eating, symptoms, or other factors. According to multiple linear regression
      analysis, supine systolic pressure, chronic obstructive pulmonary disease (COPD),
      and diabetes mellitus were associated with a decrease in systolic pressure on
      standing. Hypertension, antiarthritic drugs, and abnormal heartbeat were
      associated with an increase in systolic pressure on standing. For orthostatic
      diastolic pressure changes, supine diastolic pressure and COPD were associated
      with a decrease in diastolic pressure on standing. Congestive heart failure was
      associated with an increase in standing diastolic pressure. Using logistic
      regression analysis, only supine systolic pressure was associated with a greater
      than 20-mm Hg drop in systolic pressure (n=53, prevalence=13%). Supine diastolic
      pressure and COPD were the only variables associated with a greater than 20-mm Hg
      drop in diastolic pressure (n=16, prevalence=4%). These factors may help
      physicians in identifying older persons at risk for having orthostatic
      hypotension.

PMID- 9587086
TI  - Racial differences in cardiac catheterization use and appropriateness.
AB  - The authors sought to investigate the role of medical appropriateness as a
      potential explanatory factor in previously observed interracial cardiac procedure
      rate differences. A retrospective cohort study using RAND appropriateness
      criteria was conducted at a Veterans Affairs medical center among a sample of
      patients who were evaluated for cardiovascular disease during 1993 (n=200). All
      participants were men and 50% were black (mean age=61.8 years). Blacks were less
      likely than whites to undergo cardiac catheterizations (CC) (odds ratio
      [OR]=0.23, P < 0.01). When RAND criteria were applied, blacks were found to have
      fewer indications that made them appropriate candidates for CC and more
      indications making them inappropriate candidates for CC (chi-square test, P <
      0.05). No CC procedure underuse was found among blacks, whereas 10% of CC overuse
      was found among whites. Interracial CC procedure use differences were not due to
      procedure underuse among blacks but were in part due to overuse among whites.

PMID- 9587087
TI  - Complement component C9 enhances the capacity of beta-lactam antibiotics to kill
      Escherichia coli in vitro and in vivo.
AB  - Complement component C9 is required for rapid complement-mediated killing of
      Escherichia coli. In this report, the influence of supplemental C9 on the
      bactericidal and protective effects of beta-lactam antibiotics in neonates was
      assessed. By rocket immunoelectrophoresis, the intrinsic C9 concentrations of
      pooled serum from both human and rat neonates was less than 20% of adult levels.
      Supplemental C9 purified from human plasma enhanced the capacity of ampicillin
      treated serum from human neonates to impair the survival of E coli O7:K1:NM (P <
      0.02). Similarly, supplemental C9 enhanced the capacity of cefotaxime-treated
      neonatal rat serum to impair the survival of E coli O1:K1:NM (P < 0.05).
      Moreover, the intraperitoneal administration of C9 enhanced the survival of
      cefotaxime-treated neonatal rats that were septic with E coli (P < 0.05). These
      observations may contribute to the development of new strategies, such as
      augmentation of complement component serum concentrations, to reduce the
      morbidity and mortality of neonatal E coli sepsis.

PMID- 9587088
TI  - Citrobacter freundii empyema in a patient with occult pulmonary histoplasmosis.
AB  - The genus Citrobacter includes three species of organisms that are uncommonly
      associated with human infection. When they are pathogenic, there are usually one
      or more associated respiratory, urinary, skin-soft tissue, and central nervous
      system infections and neonatal sepsis. These infections occur in the wake of
      significant systemic illness or complicate antibiotic usage. Rarely, infection
      has been associated with active tuberculosis. The authors report a case of
      Citrobacter freundii empyema in a patient with occult pulmonary histoplasmosis.

PMID- 9587089
TI  - Colonic volvulus and ulcerative jejunoileitis due to occult celiac sprue.
AB  - Colonic volvulus is a rare complication of celiac disease. A case is reported of
      a 46-year-old man with a long-standing history of diarrhea and abdominal
      distention with a diagnosis of irritable bowel syndrome. After an elective
      inguinal hernia repair, a cecal volvulus and an ulcerative jejunoileitis
      developed in the patient that required an extensive intestinal resection. Short
      bowel syndrome developed and was treated with total parenteral and enteral
      nutrition. The patient had a poor course after reinitiation of oral diet.
      Subsequently, celiac sprue was diagnosed and the patient improved with a gluten
      free diet.

PMID- 9587090
TI  - Acute renal failure due to sulfinpyrazone.
AB  - A case of sulfinpyrazone-associated acute renal failure is reported.
      Sulfinpyrazone can cause reversible acute renal failure from acute tubular
      necrosis in patients with volume depletion. Brown tubular casts on urine
      microscopy and a fractional excretion of sodium greater than 1 are helpful in the
      diagnosis. Uric acid nephropathy and allergic interstitial nephritis should be
      included in the differential diagnosis of sulfinpyrazone-associated acute renal
      failure. Acute reduction of renal blood flow due to inhibition of renal
      prostaglandin synthesis and kallikrein activity by the drug is a possible
      mechanism. Treatment of sulfinpyrazone-induced acute tubular necrosis consists of
      intravascular hydration, supportive care, and withholding sulfinpyrazone. The
      patients at risk for acute renal failure due to sulfinpyrazone are those who have
      intravascular volume depletion as sensed by the kidneys.

PMID- 9587091
TI  - Perspectives on coronary stenting.

PMID- 9587092
TI  - Southwestern Internal Medicine Conference. Keeping travelers healthy.

PMID- 9587093
TI  - Renovascular disease in blacks: prevalence and result of operative management.
      Consortium of Southeastern Hypertension Control.
AB  - Hypertension in blacks differs in a quantitative sense from hypertension in
      whites; it occurs in blacks with greater frequency and severity and at a younger
      age when compared with whites. In addition, elevated blood pressure at any level
      is associated with increased cardiovascular morbidity and mortality in black
      patients. Several mechanisms have been suggested to account for this form of
      hypertension, implying that hypertension in black patients is intrinsically
      different from that in whites. Although these mechanisms remain unproven, it has
      generally been accepted that correctable renovascular disease and renovascular
      hypertension (RVH) occur infrequently in blacks; the authors, however, will
      review preliminary population-based data which suggest that the presence of renal
      artery disease is not determined by race or ethnicity. In addition, the
      prevalence of renovascular disease in a large group of consecutive hypertensive
      subjects will be presented. Finally, the blood pressure and renal function
      response after surgical renal artery repair in blacks will be compared with
      whites treated at the authors' institution. Taken collectively, these data and
      clinical experience support the search for and treatment of renal artery disease
      in properly selected hypertensive blacks.

PMID- 9587094
TI  - American Cancer Society National Conference on Purchasing Oncology Services:
      current methods and models in the marketplace. Chicago, Illinois, USA. September
      11-12, 1997. Proceedings.

PMID- 9587095
TI  - Medicare coverage for oncology services.
AB  - Medicare's mission is to assure health care security for our beneficiaries. Title
      XVIII of the Social Security Act (the Act) provides the Health Care Financing
      Administration (HCFA) with the authority to fulfill this mission. Although
      Medicare is considered a defined benefit program, the Act vested Medicare with
      the discretionary authority to make specific policy decisions when necessary.
      HCFA's discretionary authority, which is found at section 1862(a)(1)(A) of the
      Act, enables HCFA to provide coverage for services that are reasonable and
      necessary for the treatment and diagnosis of illness or injury or to improve the
      functioning of a malformed body member. To determine whether a service is
      reasonable and necessary, HCFA relies on authoritative evidence. This evidence
      includes, but is not limited to, approvals from appropriate federal agencies,
      such as the Food and Drug Administration, and systematic evaluations of
      scientific literature via technology assessments. HCFA also may decide that a
      service warrants a unique type of coverage policy, which is referred to as
      coverage with conditions. This form of coverage is a middle ground between strict
      noncoverage and general coverage for a medical service that appears promising,
      but still is evolving. All these policy specifications effect Medicare coverage
      of oncology services. This means that reasonable and necessary diagnostic and
      therapeutic cancer-related services that are not otherwise prohibited by
      Medicare's statute, regulations, and manual instructions are covered and paid for
      by the program. Prior to the Balanced Budget Act of 1997 (BBA '97), Medicare
      provided coverage for some beneficiaries to undergo mammography and Papanicolaou
      smear screening. As a result of BBA '97, Congress has mandated expanding coverage
      for these services as well as adding coverage for pelvic examinations, prostate
      cancer screening, colorectal screening, and antiemetic drugs used as part of an
      anticancer chemotherapy regimen. Other specific coverage policies that relate to
      cancer treatment include coverage for Group C cancer drugs and off-labeled use of
      some drugs. HCFA is committed to providing its beneficiaries with quality health
      care services and will continue to monitor the progress of oncology services with
      an eye to establishing national policies for those services that demonstrate
      through authoritative evidence that they are reasonable and necessary.

PMID- 9587096
TI  - The Oregon Health Plan: development and implementation of an innovative method of
      delivery of health care services to the medically indigent.
AB  - BACKGROUND: Health care for the medically indigent under the federal Medicaid
      system often provides care for only a fraction (ranging from 20% to 80%) of the
      poor who nominally qualify for care. Oregon has developed a unique system that
      replaces such a system with one that provides a comprehensive complement of
      medical care for all the poor but limits the care to conditions and procedures on
      a prioritized list. METHODS: The Health Services Commission, a group of
      physicians, nurses, and public representatives, developed a list of over 740
      diagnoses-treatment pairs and, with considerable public input, prioritized them
      in order of importance. The principal values used to develop the list were the
      prevention of death and the cost of the disease and its treatment. In the final
      ordering of the diagnosis-treatment pairs, public health and prevention of
      morbidity was also considered. Cancer diagnoses, and indeed all diseases, were
      not singled out for special consideration in this process. The Oregon Health Plan
      was implemented in 1994 with funds to cover 606 of 743 listed diagnoses.
      Diagnoses involving cancer were nearly all covered within these 606 items. The
      principal exception was coverage for Curative Treatment for Cancer when the
      likelihood for success was less than 5%. RESULTS: The prioritized list has met
      its goal of comprehensive medical care for the indigent population. The number of
      medically uninsured Oregonians has fallen significantly, and there have been few
      complaints about the Plan. Cancer care has been delivered to Oregon Health Plan
      clients with very few complaints or appeals of decisions concerning coverage.
      Palliative care is provided under a number of covered lines, as are curative
      medical and surgical treatment. CONCLUSIONS: The Oregon Health Plan represents an
      alternative method for delivering medical care, including the full range of
      cancer care, to the indigent. As there are limited funds in all state systems,
      the citizens of Oregon have decided to provide care using a prioritized list to
      allow provision of medical care to the entire Medicaid population. Such a plan
      represents a viable alternative to the more common method of providing everything
      but only to a limited number of poor citizens.

PMID- 9587097
TI  - A government purchaser perspective: TennCare--strengthening the safety net.
AB  - BACKGROUND: On January 1, 1994, in response to escalating Medicaid costs, the
      State of Tennessee implemented TennCare, a statewide managed health care system
      for three population groups: Medicaid eligibles, uninsurable individuals, and
      people who lacked access to insurance through their place of employment. METHODS:
      Under the TennCare program, the State contracts with ten managed care
      organizations to provide a comprehensive benefit package to each enrollee.
      Preventive services are exempt from copayment or deductible requirements. Each
      patient is assigned to a primary care provider who is responsible for assuring
      that the enrollee receives preventive services. RESULTS: More than 400,000
      previously uninsured and uninsurable persons now receive health care coverage
      through the TennCare program. An extensive quality assurance program monitors
      managed care organization service delivery, with particular emphasis on
      prevention and access. Effective case management, combined with an enrollment
      cap, have enabled the program to grow at a predictable rate, without exceeding
      the annual rate of growth of state revenues. CONCLUSIONS: The TennCare program
      has been successful in using the savings experienced during the shift from a fee
      for-service to a managed care Medicaid program to expand coverage to previously
      uninsured populations.

PMID- 9587098
TI  - Oncology management by the "new" Veterans Health Administration.
AB  - BACKGROUND: The Veterans Health Administration (VHA) of the Department of
      Veterans Affairs (VA) manages the largest integrated health care system in the
      U.S. Cancer is second only to cardiovascular disease as a cause of patient
      mortality and morbidity. In the fiscal year 1996, malignancies accounted for
      49,270 primary diagnoses at the time of discharge from acute hospitals. METHODS:
      VHA recently developed a national, uniform benefits package that provides
      oncologic services of prevention and screening, inpatient and outpatient
      services, rehabilitative care, reconstructive surgery, home health care, respite,
      and hospice care. VA classifies all hospitals according to American College of
      Surgeons (ACS) Commission on Cancer criteria and standards. One hundred four of
      173 facilities are ACS-approved cancer centers. Eighty-six VA hospitals have
      cancer registries. RESULTS: VHA has developed a Prevention Index (PI) that
      consists of nine measures for prevention and early detection of influenza and
      pneumococcal diseases, tobacco consumption, alcohol abuse, and cancers of the
      breast, cervix, colon, and prostate. All cancer interventions in the PI showed
      substantial increases between 1996 and 1997, and all exceeded U.S. Public Health
      Healthy People 2000 goals. The Veterans Health Administration's performance
      measure regarding end-of-life planning calls for 95% of eligible patients to
      receive ongoing care. Current baseline performance is 52% nationally. Measures of
      patient satisfaction for oncology patients show overall satisfaction at 87%.
      CONCLUSIONS: The VA healthcare system has substantial expertise in the diagnosis
      and management of cancer. VHA's unprecedented transformation into a system of
      integrated networks supports and promotes that expertise. The VHA initiatives
      described in this article are synergistically working to enhance the consistency
      and comprehensiveness of high-quality, patient-centered oncologic services.

PMID- 9587099
TI  - Oncology services: the Department of Defense perspective.
AB  - The Department of Defense (DoD) military health system has responsibility for
      providing medical care for more than 8 million beneficiaries. This article
      discusses initiatives related to both the providing and purchasing of oncology
      services. A description of health care coverage under TRICARE, the Department's
      managed care program, which utilizes military treatment facilities and civilian
      health care providers, is provided. Participation in clinical trials by the DoD
      beneficiaries, oncology services in military treatment facilities, quality
      management programs, cancer research, and the development of new technologies to
      enhance early cancer detection are presented. Access to research trials and new
      technologies is necessary for a comprehensive approach to cancer care. Clinical
      trials have been the vehicle by which the oncology community developed most of
      its formal clinical evidence for the efficacy of various treatment approaches.
      The Department participates in clinical trials through cooperative group
      membership or affiliation. Through an interagency agreement with the National
      Cancer Institute, DoD beneficiaries have available the option of participating in
      NCI-sponsored clinical trials through the direct military care system or through
      civilian care with reimbursement for approved protocols nationwide. The DoD has
      been actively involved in breast cancer research since 1992 and prostate and
      ovarian cancer research since 1997. The goals of the cancer research programs are
      to expedite and facilitate breakthroughs in research, support innovative, and
      exploratory ideas with a vision to foster new directions, address neglected
      issues, and bring new investigators into the research arena. The program
      incorporates the consumer perspective by involving consumers in the decision
      making process. The DoD health care system trains experts in the management of
      cancer patients and provides a multidisciplinary approach to care through the
      direct military health care system or through network providers as part of the
      TRICARE system. Although cost containment is key, the delivery of high quality
      health care that is easily accessible is a primary goal of the military health
      system. Provision of a comprehensive benefits package that includes a spectrum of
      care and employing outcomes measurements to evaluate care that is appropriate for
      the patient's disease is essential.

PMID- 9587100
TI  - Performance measurement in cancer care: uses and challenges.
AB  - Unnecessary, inappropriate, and futile care are given in all areas of health care
      including cancer care. Not only does such care increase costs and waste precious
      resources, but patients may have adverse outcomes when the wrong care is given.
      One of the ways to address this issue is to measure performance with the use of
      administrative data sets. Through performance measurement, the best providers can
      be chosen, providers can be rewarded on the basis of the quality of their
      performance, opportunities for improvement can be identified, and variation in
      practice can be minimized. Purchasers should take leadership role in creating
      data sets that will enhance, clinical performance. Specifically, purchasers
      should require the following from payers: 1) staging information; 2) requirements
      and/or incentives for proper International Classification of Diseases coding,
      including other important (comorbid) conditions; 3) incentives or requirements
      for proper data collection if the payer is using a reimbursement strategy that
      places the risk on the provider; and 4) a willingness to collect and report
      information to providers of care, with a view toward increasing quality and
      decreasing the costs of cancer care. Demanding better clinical performance can
      lead to better outcomes. Once good data is presented to patients and providers,
      better clinical behavior and improved cancer care systems will quickly follow.

PMID- 9587101
TI  - Using the tail to wag the dog: a consumer's perspective on management of the cost
      of cancer.
AB  - This article describes the health insurance policy used by one, small, fully
      insured company. The most important benefits for reducing the human and financial
      cost of cancer are benefits that improve the decision processes of the healthy
      person, and a benefit that promotes involvement of a primary care physician at
      the time of death. These benefits in our health insurance plan are designed to:
      1) assure easy access to a primary care physician; 2) provide incentives to teach
      the beneficiary to use the knowledge of the primary care physician as he/she
      makes decisions regarding care; 3) provide claims monitoring to identify small
      problems before they become serious; and 4) eliminate factors such as capitation
      and physician profiling, which provide strong financial incentives for the
      primary care physician to disengage from the care of seriously ill patients. Once
      serious illness is identified, it is important to pay generously for the person's
      struggle to regain health. The strategy described in this article does not rely
      on networks or negotiations with providers, and therefore can operate uniformly
      throughout the U.S. All large companies using this strategy to date have
      experienced a permanent drop in health care costs, largely due to a reduction in
      the incidence of expensive cases.

PMID- 9587102
TI  - Collaborative approaches to purchasing and managing oncology services for a
      prepaid population.
AB  - BACKGROUND: Change created by managed care plans is producing tensions among
      oncology care providers, health plans, patients, and employers. Managed care
      plans, which now are dominant, are engendering concern among some patients and
      providers because those plans limit provider choice and reimbursement, as well as
      inject themselves in clinical decision-making. Collaborative approaches to
      purchasing and managing oncology service for a prepaid population should help
      reduce these tensions. METHODS: This article provides a case history of how
      Harvard University Health Services, a managed care delivery and insurance program
      serving the university collaborates with contracted oncology providers. The
      described approach defines mutually beneficial payment and shared responsibility
      for care in the context of patient centered values. As a part of this
      collaborative effort, liberal experimental treatment coverage is offered.
      RESULTS: Patient care is improved because the flow of clinical information among
      caregivers is improved. When communication is more open, nurse case managers who
      work for the managed care plan also can arrange for covered services in a more
      expeditious manner. CONCLUSIONS: Collaboration among health plans, oncologists,
      and other health care providers to provide patients with high quality, cost
      effective care on a fully informed basis is challenging, but not impossible. The
      key is to define common ground and commitment to the needs of patients among
      health plans and providers.

PMID- 9587103
TI  - What the private sector does not know about purchasing oncology services.
AB  - BACKGROUND: Oncology, as a medical specialty, is usually purchased as part of a
      comprehensive health care plan offered by a health care network or carrier and is
      given the same weight in purchasing decisions as all other specialties.
      Individual practitioners and care facilities generally meet contemporary
      availability and quality standards. More detailed information generally is not
      sought and may be difficult to communicate to participants. The cost of network
      care is the most consistent and easy variable to obtain. Providing health plan
      participants with contemporary treatment information in any specialty area
      requires consistent information flow and presumes the ability to communicate this
      information to participants. METHODS: Providing credible information regarding
      prevention protocols, success rates for treatment modalities, remission data, and
      support therapies will help better educate private sector purchasers. More can be
      done to highlight clinical research and present this information in readily
      understandable terms. RESULTS: More detailed information could have an impact on
      the future design of network-based health care plans and could assist
      participants in selecting among several networks. Quality of life issues would be
      supported by comprehensive information leading to personal life-style decisions.
      CONCLUSIONS: Private purchasers need to work with oncologic professionals, care
      networks, and health carriers to develop more precise information regarding
      oncologic care specifically and to become better educated regarding each area of
      specialty care in general. Information, once available, must be available to
      participants in terms that are easy to understand.

PMID- 9587104
TI  - Oncology services for members of a national managed care company.
AB  - BACKGROUND: Oncology services in a managed care organization may be defined by
      the structure of the provider network, coverage policies, and specific health
      plan programs for oncology services. METHODS: The policies and programs of Aetna
      U.S. Healthcare were reviewed to illustrate the approach of a large, national
      health benefits company in the provision of oncology services to its members.
      RESULTS: Standard oncology services are provided by a network of independent
      participating providers, paid fee-for-service. There are no capitated
      arrangements for oncology services. The process is driven by the participating
      providers. For patients requiring bone marrow transplant or therapy available in
      few medical centers, precertification and case management are provided by the
      health plan, through the National Medical Excellence Unit. Criteria are used to
      select facilities for these services and global case rates are negotiated. In the
      health maintenance organization, educational material is distributed by the
      health plan to physicians and members to encourage the use of cancer screening
      services. In addition, reimbursement to primary care physicians can be enhanced
      by the screening rate for their members. The overall policy of Aetna U.S.
      Healthcare is to cover Phase II and III clinical trials. Coverage for Phase I
      trials or use of non-Food and Drug Administration approved drugs is based on
      reported safety and efficacy and participation in an academic program.
      CONCLUSIONS: Through arrangements with participating providers, dedicated support
      for transplant and rare cases, programs encouraging the use of cancer screening,
      and member-focused policies on coverage issues, managed care companies can
      provide complete oncology services to its membership.

PMID- 9587105
TI  - The Henry Ford Health System.
AB  - The Henry Ford Health System is a large, vertically integrated health care
      delivery system, with its core service delivery team comprised of a 1000-person
      salaried medical group. Oncology services are coordinated through its Cancer
      Center, which organizes regional distribution of oncology services for residents
      of southeast Michigan. Oncology services are delivered through five regionally
      distributed sites, affording a vast majority of cancer services to be provided
      for patients a short distance from their homes. The System owns the largest
      health maintenance organization in Michigan (Health Alliance Plan) and its
      organizational structure affords the opportunity of offering purchasers specific
      oncology service contracting opportunities. Advantages of providing comprehensive
      oncology services through an integrated health system include: 1) standardized
      cancer care guidelines, 2) medical information exchange through an electronic
      medical record, 3) interdisciplinary cancer care provided by salaried physicians,
      minimizing potentially conflicting financial issues in treatment decisions, 4)
      state-of-the-art care afforded through availability of involvement in a large
      number of National Institutes of Health-sponsored clinical trials, 5) high
      standards of credentialing for oncology physicians, and 6) integrative managed
      care perspectives and continuous attention to cost and quality of care issues.

PMID- 9587106
TI  - Overall survival of the medical oncologist: a new outcome measurement in cancer
      medicine.
AB  - BACKGROUND: Changing patterns of patient referral, decreasing payments for
      service provision, confusing network participation and reimbursement, as well as
      challenges to autonomous clinical decision-making jeopardize the traditional role
      of the oncologist in delivering cancer care. The cancer patient also may be at
      risk with unproven cancer delivery systems that displace the oncologist as
      decision-maker and care provider. The authors have constructed a model that
      preserves the oncologist's clinical and financial autonomy while meeting
      marketplace demands for improved access, decreasing costs and preserved quality
      of care. METHODS: During a 4-year period, a group of private practice medical
      oncologists initiated a formal business plan to evaluate marketplace needs, then
      designed and implemented a novel cancer care delivery model. The model required
      reconfiguring the practice into an integrated Joint Commission on Accreditation
      of Healthcare Organizations-certified cancer service corporation, providing
      medical, radiation, and gynecologic oncology. Palliative care, pain management,
      psychologic, and nutritional services were instituted as well as the vertical
      integration of home health and hospice care. Clinical pathways and treatment
      protocols were designed to enhance patient care and facilitate cost-of-care
      projections in designated populations using a cancer incidence forecasting model.
      Outcomes analysis are performed as part of ongoing continuous quality
      improvement, which continues to change this health care delivery system. RESULTS:
      In the 3 years since implementation of the model, the practice has increased from
      16 to 24 physicians, and the number of offices has increased from 12 to 17.
      Patient encounters, both new and established, have doubled. Cost of services,
      specifically hospitalization, have been reduced by 50%. Clinical research
      referrals have increased 300%. Physician compensation has improved >20%.
      CONCLUSIONS: The model created a low cost, high value provider not burdened by
      allocated overhead. Decentralized care enhanced community access, which improved
      patient compliance, enhanced patient satisfaction, decreased hospitalization, and
      thereby decreased cost. The horizontal structure permited the flexibility for
      varied purchaser products and politically sensitive physician and hospital
      provider panels. Consensus-based protocol and pathway determination achieved
      maximum physician participation, which preserved clinical and financial autonomy,
      decreased variance, and facilitated clinical research.

PMID- 9587107
TI  - The National Comprehensive Cancer Network: present and future directions.
AB  - The National Comprehensive Cancer Network (NCCN) has developed an extensive set
      of practice guidelines that cover approximately 90% of all cancer patients. These
      guidelines are steadily becoming the standard for clinical and coverage policy.
      The guideline development process is integrated directly with the development of
      a multiinstitutional data base that will permit measurement of adherence of
      practice to the NCCN guidelines and provide important clinical and other outcomes
      data. The NCCN is forming partnerships with managed care companies in the
      guideline/data base area to facilitate the delivery of more effective and
      efficient care in oncology.

PMID- 9587108
TI  - How to judge the cancer services benefit component of your health insurance plan.
AB  - BACKGROUND: Members of the oncology community, rich in data from years of
      published clinical research, epidemiology, and tumor registry information, expect
      businesses to evaluate the quality of cancer care using classic scientific
      methods. However, businesses lack sophistication in these data and tend to use
      significantly different criteria relating to cost, service, and access.
      Logistical problems also abound, such as the wide variety of cancers, small
      sample sizes, and the frequency with which patients change insurance plans.
      METHODS: Adapting an approach first proposed by Donabedian employing criteria
      that can be measured, easily gathered, and whose presence/absence can be
      interpreted as having a consequence for patient care, the author proposes a
      system of evaluating cancer health care benefits. CONCLUSIONS: Recognizing that
      classic outcomes analysis is too complex and inappropriate for business,
      companies and oncology providers may be able to develop obtainable measures whose
      presence or absence has intuitive and documented relation to the quality of
      cancer care.

PMID- 9587109
TI  - Managed oncology care: the disease management model.
AB  - BACKGROUND: As oncology becomes an increasing financial burden on the U.S. health
      care system, effort is being focused on finding methods to more effectively
      deliver, manage, and monitor the highly complex panoply of cancer care services
      required by patients. This issue has growing significance and importance in light
      of an aging U.S. population and the rapid penetration of managed care. METHODS:
      SalickNet, Salick Health Care's disease management and managed care company, has
      been a pioneer in the development and implementation of cancer disease management
      programs. The cornerstone is a proprietary computer-based disease management
      system called OMARS (Oncology Management Assessment Reporting System). The
      flexible yet sophisticated architecture allows for the management of integrated
      care, data processing, and the generation of compelling custom reporting,
      fulfilling the goal of maximizing coordinated and effective patient care.
      CONCLUSIONS: Based on data collected and analyzed across critical clinical,
      quality of life, and patient satisfaction outcome measures, strong evidence
      exists that the SalickNet Disease Management Model is a highly effective vehicle
      for bringing about cost, quality, and outcomes advantages in cancer care.

PMID- 9587110
TI  - Delivery of comprehensive cancer care at Kaiser Permanente.
AB  - BACKGROUND: Kaiser Permanente (KP) is a large health maintenance organization
      (HMO) operating in 14 states and caring for 8,000,000 members in hundreds of
      facilities staffed by thousands of physicians and support personnel. Cancer care
      is provided to these KP members as part of the health care package. METHODS: KP
      insures members for all their health care needs and provides needed services in
      their own facilities except in rare circumstances. Professional services are
      provided by physicians of the Permanente Medical Groups, locally governed groups
      of physicians contractually bound to Kaiser Permanente by capitation agreements.
      These agreements cover the full range of services for cancer and all other
      diseases. KP uses evidence-based guidelines to rationalize the provision and
      delivery of medical care for its members. A large investment in technology has
      allowed these guidelines to be generally available on local intranets and has
      facilitated the development of a computerized medical record and linkages to
      multiple clinical and administrative databases for all providers. Several of the
      KP regions have strong commitments to research in the public domain and have
      integrated this effort into the clinical practice of oncology, particularly in
      clinical trials in cancer treatment and prevention. Research efforts also exist
      in the areas of cancer epidemiology and outcomes. RESULTS: Cancer care is
      integrated fully into the comprehensive medical care provided the KP member.
      Health benefits cover the full range of cancer prevention and treatment without
      distinction by diagnosis. CONCLUSIONS: Within the broad range of health care
      options in the U.S., KP represents a good example of the value of a large HMO to
      deliver comprehensive general medical and oncologic care.

PMID- 9587111
TI  - Population screening for colorectal carcinoma with fecal-occult blood testing:
      are we sufficiently informed?

PMID- 9587112
TI  - Microsatellite instability in human solid tumors.
AB  - BACKGROUND: Microsatellite instability (MIN) has been identified in a wide
      variety of human tumors, both familial and sporadic. In this study the authors
      attempted to correlate MIN with other biologic parameters to assess the
      significance of MIN in cancer. METHODS: The current literature up to May 1997 was
      reviewed critically. Comparative assessment and analysis of published MIN data in
      human solid tumors was addressed. RESULTS: Based on review of the current medical
      literature, the following conclusions can be drawn: 1) MIN associated with
      inherited mutations of the DNA mismatch repair genes (predominantly hMSH2/hMLH1)
      appears to characterize only the hereditary nonpolyposis colon carcinoma
      (HNPCC)/Muir-Torre family cancer syndrome category, and a subset of young
      colorectal carcinoma patients. Constitutional hMSH2/hMLH1 mutations rarely are
      reported in other than colon MIN+ tumor types; 2) MIN in non-HNPCC tumors
      generally is not associated with somatic mutations in the mismatch DNA repair
      genes most commonly involved in HNPCC; 3) loci of individual chromosomes
      containing microsatellite markers demonstrating high MIN frequency may be linked
      to particular tumor types (tumor specific MIN hot spots); 4) the gel banding
      patterns of MIN observed in noncolon tumors differ significantly from those
      reported previously in HNPCC; 5) although overall no association between MIN and
      histopathology is observed in the literature, a statistically higher MIN
      frequency has been noted in certain tumor subtypes; and 6) MIN in tumors can be
      associated with early or late stages of tumor progression, and also has been
      found in nontumor tissues. CONCLUSIONS: Molecular diagnosis using MIN analysis
      has been documented in at least two types of tumors (HNPCC and sporadic bladder
      carcinoma), suggesting a potential role of MIN in the diagnosis and/or prognosis
      of other solid human tumors as well.

PMID- 9587113
TI  - Recombinant interferon-alpha therapy in patients with follicular lymphoma.
AB  - BACKGROUND: Advanced stage, follicular, non-Hodgkin's lymphoma (NHL) has no cure
      and no single standard of care. Remissions induced by standard chemotherapy
      regimens generally are not durable and, with the exception of selected patients
      with limited early stage disease, most patients with follicular NHL eventually
      die of their disease. Recombinant interferon-alpha (rIFN-alpha) has demonstrated
      activity against follicular NHL in clinical trials. METHODS: A comprehensive
      survey of current therapeutic options for follicular NHL patients was conducted
      with emphasis on the role of rIFN-alpha used in conjunction with chemotherapy
      regimens. RESULTS: Phase III studies have demonstrated that rIFN-alpha delays
      disease progression and may improve overall survival when administered either
      with chemotherapy or as maintenance therapy after induction treatment for
      follicular lymphoma. Adverse effects from combination or maintenance regimens are
      not significantly different from those from chemotherapy alone. CONCLUSIONS:
      Recombinant IFN-alpha is safe and effective when given in conjunction with
      standard chemotherapeutic regimens in selected patients with follicular NHL, and
      may especially benefit patients with minimal residual disease after induction
      chemotherapy.

PMID- 9587114
TI  - Telomerase activity in precancerous hepatic nodules.
AB  - BACKGROUND: Recent studies have demonstrated that telomerase, a reverse
      transcriptase linked to cellular "immortalization," is activated in a variety of
      malignant human tumors. This study was conducted to determine whether telomerase
      activity represents a marker of malignant transformation in precancerous
      (dysplastic) nodules arising in patients with cirrhosis. METHODS: Telomerase
      activity was evaluated in frozen tissue samples of 14 cirrhotic liver specimens
      and 30 large nodular lesions contained therein, including 13 large regenerative
      nodules/low grade dysplastic nodules, 10 high grade dysplastic nodules, and 7
      hepatocellular carcinomas (HCCs). A modified telomeric repeat amplification
      protocol was used. RESULTS: There was a clear-cut difference in telomerase
      activity levels between HCC (positive or strongly positive) and cirrhotic liver
      samples (weakly positive or negative). The majority of large noncancerous nodules
      (86%) exhibited telomerase activity levels similar to HCCs. However, such
      activity was not limited to dysplastic lesions but also was detected in some
      large regenerative nodules. CONCLUSIONS: These findings suggest that telomerase
      activation is an early event in large nodule formation in cirrhosis, which may
      facilitate the action of other factors in the process of carcinogenesis.
      Telomerase activity in large hepatic nodules is not always indicative of
      malignant transformation.

PMID- 9587115
TI  - Histologic and biologic patterns of microscopic pancreatic ductal adenocarcinomas
      detected incidentally at autopsy.
AB  - BACKGROUND: The major clinical problems with pancreatic carcinoma are its silent
      course and late, fatal clinical manifestation. The results of treatments of small
      pancreatic carcinomas (<2 cm in greatest dimension) have led to the assumption
      that the detection of these cancers at earlier stages would lead to better
      survival and possible cure. Currently, there is no information about the
      histologic and biologic patterns of early stage pancreatic carcinoma, and the
      available data on incidentally detected tumors are fragmentary. The authors
      observed two incidental microscopic pancreatic ductal adenocarcinomas in female
      patients who died of advanced gastric carcinoma (Case 1) and renal carcinoma
      (Case 2). METHODS: The pancreatic lesions were examined histologically in serial
      sections and immunocytochemically for islet cells. Microdissection was performed
      so that the lesions could be examined for c-Ki-ras mutation. RESULTS: In Case 1,
      the pancreatic lesion was composed of cystic and solid components. The cystic
      component consisted of four small cysts compatible with a mucinous cystic tumor
      and showed no invasion. The solid component was a well-differentiated
      adenocarcinoma that occupied a 4 x 2 mm area. In Case 2, the pancreatic lesion
      contained two small, separate cysts, one of which was surrounded by two
      apparently separate, invasive adenocarcinomas 2.6 x 0.7 mm and 1.2 x 0.5 mm in
      greatest dimension. There was invasion of pancreatic islets and perineural spaces
      in both cases; and in Case 2, there was invasion of peripancreatic fatty tissue.
      In both cases, the epithelia of the cystic components and tumors showed mutation
      of the c-Ki-ras oncogene at codon 12, with GGT-to-GAT transition. CONCLUSIONS.
      Pancreatic carcinoma seems to occur under occult circumstances and maintain a
      silent course. Even in its early developmental stage, the cancer is invasive,
      primarily affects islets and nerves, and exhibits mutation of the c-Ki-ras
      oncogene. These findings call for urgency in the development of preventive
      modalities.

PMID- 9587116
TI  - Evaluation of tissue polypeptide specific antigen, CYFRA 21-1, and
      carcinoembryonic antigen in nonsmall cell lung carcinoma: does the combined use
      of cytokeratin markers give any additional information?
AB  - BACKGROUND: Recently developed tissue polypeptide specific antigen (TPS) and
      CYFRA 21-1 assays determine the soluble cytokeratin 18 and 19 fragments,
      respectively, in serum. The authors compared the value of TPS, CYFRA 21-1, and
      carcinoembryonic antigen (CEA) for the diagnosis, staging, prognosis, and
      monitoring of patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The
      study included 85 patients with benign lung diseases and 94 patients with NSCLC.
      TPS, CYFRA 21-1, and CEA serum levels were measured with commercial kits.
      RESULTS: The following were demonstrated: 1) CYFRA 21-1 and TPS levels, but not
      CEA levels, differed significantly between NSCLC patients with operable disease
      (Stages I-IIIA) and those with inoperable disease (Stages IIIB-IV). 2) The
      correlation coefficient between CYFRA 21-1 and TPS increased with the progression
      of NSCLC from Stages I-IIIA (r = 0.41, P = 0.04) to Stages IIIB-IV (r = 0.70, P <
      0.001). 3) Multivariate analysis identified TPS and CYFRA 21-1 as significant
      predictors of survival, with relative risks of 2.57 (P = 0.001) and 2.05 (P =
      0.01), respectively. For cases in which both cytokeratin markers were positive,
      the relative risk was 6.4 (P < 0.0001) compared with cases in which both were
      negative. 4) For the group with inoperable disease, the combined use of TPS and
      CYFRA 21-1 allowed for the definition of 3 sets of patients with significantly
      different median survival times (14.3 months vs. 7.4 months vs. 2.6 months). 5)
      The percentages of marker evaluations concordant with results of clinical
      assessments of response to therapy were 75.0%, 72.2%, and 61.1% for CYFRA 21-1,
      TPS, and CEA, respectively. CONCLUSIONS: These findings suggest that, for NSCLC
      patients, CYFRA 21-1 and TPS are significant prognostic factors and effective
      monitors of therapy. The combined use of these cytokeratin markers may provide
      additional information for prognosis.

PMID- 9587117
TI  - The prognostic value of soluble interleukin-6 receptor in patients with multiple
      myeloma.
AB  - BACKGROUND: The effect of interleukin-6 (IL-6), the major growth factor for
      myeloma cells, may be enhanced by soluble IL-6 receptor (sIL-6R). Therefore, the
      current study investigated the clinical significance of serum sIL-6R in patients
      with multiple myeloma (MM). METHODS: Serum levels of sIL-6R were determined by
      enzyme-linked immunoassay in 55 normal controls, 81 individuals with monoclonal
      gammopathy of undetermined significance (MGUS), and 164 patients with MM in
      various phases of the disease. RESULTS: sIL-6R concentrations were higher in MM
      patients (162.0 +/- 134.6 ng/mL) than in individuals with MGUS (58.9 +/- 36.7
      ng/mL) or in controls (45.6 +/- 22.3 ng/mL) (P = 0.0000). sIL-6R was not found to
      have a significant linear correlation with any other parameter, including IL-6,
      beta2-microglobulin (beta2-m), and neopterin, either in newly diagnosed cases or
      during the course of the disease. In addition, there were no statistically
      significant differences in sIL-6R concentrations between the clinical stages at
      the time of diagnosis. In univariate logistic regression analysis sIL-6R was a
      significant but weak prognostic indicator (P = 0.000000). Kaplan-Meier analysis
      showed that elevated levels of sIL-6R were associated with shorter survival (P =
      0.00282). Patients also were stratified according to their serum beta2-m and sIL
      6R levels. Patients with low levels of both parameters had a clear survival
      benefit over the other groups (P = 0.000000). CONCLUSIONS: The correlation
      between sIL-6R levels and survival is significant but weak, making it unlikely to
      be of much value in predicting the outcome of patients with MM alone. The results
      of the current study support the role of sIL-6R levels in improving the
      prognostic value of beta2-m and in discriminating patients with MM from
      individuals with MGUS.

PMID- 9587118
TI  - The cost-effectiveness of fine-needle aspiration cytology and 14-gauge core
      needle biopsy compared with open surgical biopsy in the diagnosis of breast
      carcinoma.
AB  - BACKGROUND: Judicious utilization of fine-needle aspiration cytology (FNAC) and
      14-gauge core needle biopsy (CB) theoretically should result in greater accuracy
      in breast carcinoma diagnosis and fewer unnecessary open surgical biopsies
      (OSBs), thus lowering health care costs. METHODS: In 1995 in Rochester, New York,
      the ratio of open surgical breast biopsies per each verified breast carcinoma
      (OSB/Ca) in a freestanding breast clinic (EWBC) was compared with the OSB/Ca
      ratio of all physicians in the remainder of the city. The EWBC differs from all
      other diagnostic facilities in Rochester in that it routinely performs FNAC and
      CB. RESULTS: The EWBC recommended 462 OSBs resulting in 310 verified carcinomas,
      for a OSB/Ca ratio of 1.5. The physicians in the remainder of the city
      recommended 2036 OSBs resulting in 513 verified carcinomas, for a OSB/Ca ratio of
      4.0. If the EWBC OSB/Ca ratio had been identical to the remainder of the city,
      the number of extra OSBs recommended by the clinic would have been 778, resulting
      in an additional cost of $1,712,082. When the added cost of the 2594 FNACs
      ($256,285) and 403 CBs ($252,278) performed by the clinic was subtracted from the
      $1,712,082, the freestanding breast clinic cost savings was $1,203,519. The lymph
      node metastasis rate of 19% for the breast carcinomas diagnosed in clinic
      patients was identical to that of the women with breast carcinoma in the
      remainder of the city. CONCLUSIONS: Utilization of FNAC and CB allows
      radiologists to lower their OSB/Ca ratio without sacrificing early detection. In
      this study, these less expensive procedures result in lowered medical costs for
      the health care system.

PMID- 9587119
TI  - Preoperative galactography increases the diagnostic yield of major duct excision
      for nipple discharge.
AB  - BACKGROUND: Although most nipple discharge is due to a benign etiology,
      approximately 10-15% is due to breast carcinoma. The standard management of
      nipple discharge includes major duct excision, and although this procedure may
      eliminate future nipple discharge, a specific etiology is not always found. This
      study investigates the utility of preoperative galactography in targeting the
      causative lesion. METHODS: During 1994-1996, 46 cases of major duct excision were
      identified from operating room records. All patients presented with spontaneous
      nipple discharge from a single duct. In 16 patients both a diagnostic galactogram
      and a preoperative galactogram with methylene blue were performed to localize the
      causative lesion and to enable intraoperative identification. Data were obtained
      by retrospective chart review. Statistical significance was determined by
      Fisher's exact test. RESULTS: Preoperative galactography was obtained in 7 of 31
      patients (23%) with bloody nipple discharge and 9 of 15 patients (60%) with
      guaiac negative discharge. All patients undergoing preoperative galactography
      were found to have either a filling defect and/or duct cutoff (n = 13) or duct
      ectasia (n = 3). All patients with a filling defect and/or duct cutoff on
      galactogram were found to have a carcinoma or papilloma at surgery. In the three
      patients with duct ectasia observed on galactogram, the diagnosis was confirmed
      at surgery. All patients who underwent preoperative galactography were found to
      have specific pathology that accounted for the nipple discharge versus 20 of 30
      patients (67%) who did not undergo preoperative galactography (P = 0.009).
      CONCLUSIONS: Although major duct excision for nipple discharge may eliminate the
      presenting symptomatology, a pathologic correlate is not always found. The data
      from the current study show that localizing the causative lesion by preoperative
      galactography increases the likelihood that specific pathology will be found at
      surgery, and suggests that preoperative galactography may be helpful in the
      evaluation and management of patients presenting with spontaneous nipple
      discharge. Cancer 1998;82:1874-80. 1998 American Cancer Society.

PMID- 9587120
TI  - Clinical application of intratumoral blood flow study in patients with
      endometrial carcinoma.
AB  - BACKGROUND: The objective of this study was to evaluate the correlation between
      intratumoral blood flow as assessed by color Doppler ultrasound with stage, tumor
      grade, depth of invasion, and lymph node metastasis in endometrial carcinoma and
      determine its clinical usefulness. METHODS: Sixty-six patients with endometrial
      carcinoma were enrolled. All patients received surgical treatment. Transvaginal
      color Doppler ultrasound was performed before surgery to detect the arterial
      blood flow signals within the tumors and the lowest resistance index (RI) was
      recorded. Formalin fixed, paraffin embedded pathology slides were reviewed by a
      senior pathologist to evaluate the histologic grading, tumor size, depth of
      myometrial invasion, and presence of lymph node metastasis. RESULTS: Intratumoral
      RI correlated well with surgical staging, histologic grading, the depth of
      myometrial invasion, and the presence of lymph node metastasis. Significantly
      lower RI was noted in tumors of advanced stage (> than International Federation
      of Obstetrics and Gynecology [FIGO] Stage I) (0.38 +/- 0.09 vs. 0.54 +/- 0.11; P
      < 0.001), tumors with higher histologic grade (Grade 3) (0.36 +/- 0.08 vs. 0.53
      +/- 0.11; P < 0.001), tumors with deep myometrial invasion (> 50% myometrial
      thickness) (0.38 +/- 0.07 vs. 0.54 +/- 0.11; P < 0.001), and tumors with lymph
      node metastasis (0.34 +/- 0.07 vs. 0.52 +/- 0.11; P < 0.001) compared with tumors
      with Stage I, Grade 1/2 histology, no or superficial myometrial invasion, and
      absence of lymph node metastasis, respectively. CONCLUSIONS: Intratumoral blood
      flow analysis assessed by color Doppler ultrasound correlates well with surgical
      stage, tumor grade, myometrial invasion, and lymph node metastasis in patients
      with endometrial carcinoma. Assessment of tumor angiogenesis using color Doppler
      ultrasound provides useful information for the preoperative prediction regarding
      stage, histologic grade, depth of myometrial invasion, and presence of lymph node
      metastasis in patients with endometrial carcinoma. The authors believe routine
      pelvic lymph node dissection should be performed for those patients whose lowest
      RI values of intratumoral blood flow are < or = 0.4 because those patients are at
      very high risk for pelvic lymph node involvement.

PMID- 9587121
TI  - Assessment of outcome prediction models for patients with localized prostate
      carcinoma managed with radical prostatectomy or external beam radiation therapy.
AB  - BACKGROUND: A clinical staging system for localized prostate carcinoma that
      provides reliable information on which management decisions regarding an
      individual patient can be based is lacking. This study compared the abilities of
      all published proposed clinical staging systems to predict time to prostate
      specific antigen (PSA) failure after radical prostatectomy or external beam
      radiation therapy for clinically localized prostate carcinoma. METHODS: A total
      of 1441 clinically localized prostate carcinoma patients who were managed with
      radical prostatectomy at the University of Pennsylvania in Philadelphia (n = 688)
      or the Brigham and Women's Hospital in Boston (n = 288) or with external beam
      radiation therapy at the Joint Center for Radiation Therapy in Boston (n = 465)
      were entered into this study. Patients who received adjuvant or neoadjuvant
      hormonal or radiation therapy were excluded. Akaike's Information Criterion (AIC)
      and Schwartz Bayesian Criterion (SBC) estimates, which are comparative measures,
      were calculated for each clinical staging system. Pairwise comparisons of the AIC
      and SBC estimates for the most predictive clinical staging systems were performed
      using a formal bootstrap technique with 2000 replications. RESULTS: Both the
      staging system based on the risk score and the staging system based on the
      calculated volume of prostate carcinoma and PSA (cVCa-PSA) optimized the
      prediction of time to posttreatment PSA failure. The cVCa-PSA system, however,
      provided a more clinically useful stratification of outcome. CONCLUSIONS:
      Improved clinical staging for patients with localized prostate carcinoma may be
      possible with parameters obtained during routine evaluation. Validation by other
      investigators is underway.

PMID- 9587122
TI  - Selective expression of inducible nitric oxide synthase in human prostate
      carcinoma.
AB  - BACKGROUND: Nitric oxide (NO) is synthesized by inducible nitric oxide synthase
      (iNOS) and plays an important role in tumor growth and angiogenesis. NO
      generation by iNOS also influences the cytotoxicity of macrophages and tumor
      induced immunosuppression. Before now, the expression of iNOS in prostate
      carcinoma tissue had not been determined. METHODS: In this study, tissue sections
      from 16 patients with prostate carcinoma were studied immunohistochemically and
      compared with tissue specimens from 10 patients with benign hyperplasia. RESULTS:
      Positive iNOS immunostaining was detected in all sections from patients with
      prostate carcinoma. The malignant epithelial cells were highly positive. The
      antibody against iNOS also marked round cells, which had the same cell shape as
      that observed for macrophages. These cells were located in stroma and epithelium
      adjacent to tumor islets. However, round cells in benign tissue stained negative
      for iNOS. None of the benign hyperplasia specimens stained positive for iNOS
      immunohistochemically. CONCLUSIONS: Prostate carcinoma tissue had a high iNOS
      content, whereas benign tissue did not. The authors suggest that epithelial iNOS
      expression can be used as a specific immunohistochemical marker for prostate
      carcinoma. NO generation by iNOS may play multiple roles in the development of
      this disease.

PMID- 9587123
TI  - Rapid screening for psychologic distress in men with prostate carcinoma: a pilot
      study.
AB  - BACKGROUND: As more oncology care is moved to the outpatient setting, the need
      for a rapid means for oncologists to identify patients with significant distress
      has increased. Concurrent with this move has been the pressure to reduce time
      spent with each patient, adding to the likelihood that a distressed patient will
      not be recognized and will remain untreated in the current health care
      environment. METHODS: A pilot program was conducted in a prostate carcinoma
      oncology clinic to test the feasibility of a two-stage approach that identifies
      patients in significant distress and refers them for treatment. Two pencil and
      paper self-report measures were used to detect psychologic distress in patients
      over the previous week: 1) The Hospital Anxiety and Depression Scale (HADS) and
      2) "The Distress Thermometer." Patients who scored above an agreed upon cutoff
      score on either measure (HADS = 15+; Thermometer = 5+) were referred to the
      psychiatric liaison in the clinic for evaluation. RESULTS: Compliance in filling
      out the measures was excellent; only 8 of 121 patients (6.6%) refused. Thirty-one
      percent of evaluable patients were referred based on elevated scores. Seventeen
      of 29 patients actually were evaluated. Eight of 17 patients met Diagnostic and
      Statistical Manual (of Mental Disorders)-IV criteria for a psychiatric disorder.
      CONCLUSIONS: This approach for rapid screening for distress was acceptable in
      prostate carcinoma patients, although these older men were reluctant to agree to
      evaluation and treatment. This simple screening method needs further testing and
      the identification of barriers on the part of the patient and oncologist that
      impede the identification of the most distressed patients.

PMID- 9587124
TI  - Pathologic seminal vesicle invasion after radical prostatectomy for patients with
      prostate carcinoma: effect of early adjuvant radiation therapy on biochemical
      control.
AB  - BACKGROUND: The authors evaluated the effect of postoperative radiation therapy
      on freedom from biochemical failure (bNED) in men with prostate carcinoma who had
      pathologic seminal vesicle invasion after radical prostatectomy and negative
      pelvic lymph node dissection (pT3cN0). METHODS: Between 1989 and 1995, 375 men
      underwent radical prostatectomy at Thomas Jefferson University Hospital. Fifty
      three men (13%) had pT3cN0 prostate carcinoma and were the subject of this
      analysis. Men in whom prostate specific antigen (PSA) could not be detected were
      deemed free of biochemical failure. RESULTS: Of the 53 men with pT3cN0 prostate
      carcinoma, 18 had an elevated PSA immediately after surgery and received salvage
      radiation therapy (RT). The 3-year bNED rate for this group was only 38%. At 3
      months, PSA could not be detected in the other 35 men. Fifteen of those 35 men
      underwent early adjuvant RT, and the other 20 were observed for biochemical
      failure. The 3-year bNED rate for the 15 patients treated with immediate adjuvant
      RT was 86%, compared with 48% for the 20 men who were observed (P = 0.01).
      CONCLUSIONS: These data suggest that early adjuvant RT for men with pT3cN0
      prostate carcinoma and no detectable PSA postoperatively reduces the likelihood
      of future biochemical failure. Men with pT3cN0 prostate carcinoma and a
      persistently elevated postoperative PSA level are less likely to benefit from RT
      and should be considered for systemic therapy.

PMID- 9587125
TI  - Management of recurrent meningeal hemangiopericytoma.
AB  - BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high
      propensity for recurrence. The purpose of this study was to analyze the efficacy
      of different treatment options in patients with recurrent disease. METHODS: The
      records of all patients with recurrent meningeal hemangiopericytoma treated at
      the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four
      consecutive patients were studied. The mainstay of treatment was brain surgery in
      21 patients (62%); the median time to recurrence from surgery was 12 months. Ten
      patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by
      stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all
      with lesion size < 25 mm) achieved a complete response, which persisted at a
      median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a
      median duration of 12 months, whereas 3 lesions (15%) remained stable. Two
      patients with inoperable CNS lesions received external beam radiation therapy and
      both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received
      radiation therapy for metastatic disease. Of these, seven patients remained
      stable with good symptomatic relief, and two patients experienced tumor
      progression. Chemotherapy with doxorubicin-containing regimens was administered
      in 7 patients (21%); there was only 1 PR that lasted 8 months. The median
      survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is
      important for the successful treatment of patients with recurrent meningeal
      hemangiopericytoma. Radiosurgery plays a definite role in the treatment of
      smaller recurrent CNS lesions. Radiation therapy is helpful in the management of
      inoperable tumors. More effective chemotherapeutic agents are needed.

PMID- 9587126
TI  - Expression of the neural cell adhesion molecule in astrocytic tumors: an inverse
      correlation with malignancy.
AB  - BACKGROUND: Cell adhesion molecules are among the key factors in the development
      of the malignant potential of brain tumors. The aim of this study was to
      investigate the expression of the neural cell adhesion molecule (NCAM) in human
      astrocytic tumors and assess any relationship between NCAM expression and the
      degree of malignancy. METHODS: The expression of NCAM was examined in 52
      astrocytic tumors by Western blot analysis. From them the authors selected 23
      adult supratentorial ordinary astrocytic tumors and performed quantitative
      Western blot analysis for each isoform (NCAM 172-180, NCAM 145, NCAM 125-130) to
      investigate any correlation between the expression of each NCAM isoform and the
      histologic and biologic malignancy (histology, proliferating cell indices [PCIs]
      determined by MIB-1 immunohistochemistry, and manifestation on magnetic resonance
      images [MRIs]). Immunohistochemistry with antihuman NCAM monoclonal antibody was
      also performed on the tumors from which cryostat sections were available.
      RESULTS: Most of the astrocytomas and anaplastic astrocytomas revealed 3 bands at
      180, 145, and 125-130kD, whereas in glioblastomas the bands tended to diminish.
      The expression of each NCAM isoform in astrocytic tumors decreased in proportion
      to the progression of the histologic malignancy, and the results were also
      corroborated by immunohistochemical evaluation. An inverse correlation was also
      observed between the amount of NCAM expression and MIB-1 PCIs. NCAM expression
      was hardly detectable in those tumors with highly invasive manifestation on MRIs.
      CONCLUSIONS: To the authors' knowledge, this study provides the first direct
      evidence that NCAM is down-regulated in the development of the malignancy of
      astrocytic tumors; and it is suggested that reduced NCAM expression might be
      involved in the development of biologic malignancy.

PMID- 9587127
TI  - How tumor stage affects surgeons' surveillance strategies after surgery for
      carcinoma of the upper aerodigestive tract.
AB  - BACKGROUND: The factors that influence decision-making among surgeons are not
      well understood. The authors evaluated how tumor stage in otherwise healthy
      patients subjected to potentially curative surgery for upper aerodigestive tract
      (UADT) epidermoid carcinoma affects the self-reported follow-up strategies
      employed by practicing surgeons. METHODS: Hypothetical patient profiles and a
      detailed questionnaire based on these profiles were mailed to the 824 members of
      the Society of Head and Neck Surgeons (SHNS) and the 522 members of the American
      Society for Head and Neck Surgery who were not members of SHNS. The effect of TNM
      stage on the surveillance strategies chosen by the respondents was analyzed.
      RESULTS: Ten of the 14 most commonly employed surveillance modalities were
      ordered significantly more frequently with increasing TNM stage. This effect
      persisted through 5 years of follow-up, but the differences across stages were
      small. Only 30% of respondents modified their strategies according to the
      patient's TNM stage. CONCLUSIONS: Most surgeons performing surveillance after
      potentially curative surgery in otherwise healthy patients with UADT carcinoma
      use the same follow-up strategy irrespective of TNM stage. These data permit
      rational design of a randomized clinical trial of two alternate follow-up plans.

PMID- 9587128
TI  - A randomized, controlled clinical trial to evaluate the effects of zinc sulfate
      on cancer patients with taste alterations caused by head and neck irradiation.
AB  - BACKGROUND: In uncontrolled clinical trials, the administration of oral zinc
      sulfate has been reported both to prevent and correct taste abnormalities in
      cancer patients receiving external radiotherapy (ERT) to the head and neck
      region. METHODS: Eighteen patients were randomized to receive either zinc sulfate
      tablets (a dose of 45 mg) or placebo tablets three times a day at the onset of
      subjective perception of taste alterations during the course of ERT and up to 1
      month after ERT termination. Taste acuity was determined by measuring detection
      and recognition thresholds for four taste qualities. Intolerance of zinc sulfate
      or placebo administration was investigated, and the oral cavity was examined. All
      the evaluations were studied prior to, at weekly intervals during, and 1 month
      after ERT administration. RESULTS: Taste acuity for one or more taste qualities
      was already impaired before ERT. During ERT treatment, taste alterations were
      experienced at least once for a minimum of 3 of the 8 measured thresholds by 100%
      of the patients, and 33.3% of the patients became aware of some alteration within
      the first week of treatment. The patients treated with placebo experienced a
      greater worsening of taste acuity during ERT treatment compared with those
      treated with zinc sulfate. One month after ERT was terminated, the patients
      receiving zinc sulfate had a quicker recovery of taste acuity than those
      receiving placebo. Statistically significant differences between the two groups
      emerged for urea detection and sodium chloride recognition thresholds during ERT
      treatment and for sodium chloride, saccharose, and hydrogen chloride recognition
      thresholds after the termination of ERT treatment. CONCLUSIONS: This
      pharmacologic therapy is effective and well tolerated; it could become a routine
      in clinical practice to improve the supportive care of patients with taste
      alterations resulting from head and neck cancer.

PMID- 9587129
TI  - Systemic chemotherapy alone for patients with non-acquired immunodeficiency
      syndrome-related central nervous system lymphoma: a pilot study of the BOMES
      protocol.
AB  - BACKGROUND: Anecdotal reports have suggested that systemic chemotherapy with
      agents that better cross the blood-brain barrier may result in long term disease
      remission in some patients with central nervous system (CNS) lymphoma. This
      treatment strategy has the advantage of sparing patients the late neurologic
      complications from brain irradiation. METHODS: Eligible patients were required to
      1) have tissue-proven and measurable non-acquired immunodeficiency syndrome
      (AIDS)- related primary or metastatic CNS lymphoma; 2) have normal hemogram,
      renal function, and hepatic function; 3) be age < or = 75 years; and 4) have
      provided informed consent. Patients with lymphoblastic lymphoma or patients who
      previously had been exposed to nitrosoureas, etoposide, or high dose methotrexate
      were not eligible. The systemic chemotherapy (BOMES regimen) included carmustine,
      65 mg/m2/day, intravenously (i.v.) on Days 1-2; vincristine, 2 mg/day, i.v. on
      Days 1 and 8; methotrexate, 1.5 g/m2, i.v. on day 15 followed by leucovorin
      rescue; etoposide, 50 mg/m2/day, i.v. on Days 1-5; and methylprednisolone, 200
      mg/day, i.v. on Days 1-7; repeated every 4 weeks (BOMES regimen). Four doses of
      intrathecal methotrexate were given to patients who had involvement in the
      cerebrospinal fluid. RESULTS: Between March 1991 and March 1997 a total of 19
      patients were enrolled on the study. There were 13 men and 6 women, with a median
      age of 57 years. Fourteen patients had primary CNS lymphoma and 5 patients had
      concurrent extra-CNS lymphoma. Nine patients previously had been treated by
      radiotherapy (four patients), chemotherapy (three patients), or both (two
      patients). There were 11 complete remissions (CR) (57.9%) and 5 partial
      remissions (26.3%), with a total remission rate of 84.2%. One patient had had
      progressive brain lymphoma during systemic chemotherapy with the conventional
      cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen, but
      achieved CR soon after the regimen was changed to BOMES. The median time to
      progression of the responders was 6 months. At last follow-up, 4 patients were
      alive without lymphoma at 10, 47, 64, and 66 months, respectively. There were two
      treatment-related deaths due to sepsis. Another two patients died of fulminant
      hepatitis that most likely was chemotherapy-related reactivation of chronic B
      viral hepatitis. CONCLUSIONS: The authors believe systemic chemotherapy alone may
      result in long term disease remission in some select patients with non-AIDS
      related CNS lymphoma. Further investigation for better protocols is mandatory.

PMID- 9587130
TI  - A multivariate analysis of the survival of patients with aggressive lymphoma:
      variations in the predictive value of prognostic factors during the course of the
      disease. Groupe d'Etudes des Lymphomes de l'Adulte.
AB  - BACKGROUND: Aggressive non-Hodgkin's lymphoma is now often curable with
      chemotherapy. The International Prognostic Index (IPI) was recently developed to
      predict patient survival on the basis of pretreatment clinical features. However,
      classical multivariate regression models such as the IPI fail to detect time
      dependent changes in the predictive value of covariates. In this study, an
      extension of the Cox proportional hazards model was used to determine whether the
      value of prognostic factors might decay over time. METHODS: A total of 1271
      patients younger than 60 years, entered on the LNH-84 and LNH-87 studies of an
      ACVBP induction regimen (consisting of doxorubicin, cyclophosphamide, vindesine,
      bleomycin, methylprednisolone, and IT methotrexate), were analyzed in terms of
      overall survival and monthly risk of dying. By a standard method, prognostic
      factors were identified in a training sample and confirmed in a validation
      sample. The independently significant covariates were then included in a step
      function regression model (3-step) that permitted determination of their value in
      predicting the short term and long term survival of the entire population.
      RESULTS: During the entire follow-up period (median, 5.5 years), lactate
      dehydrogenase level, tumor stage, performance status, and number of extranodal
      sites remained independently predictive of overall survival. However, these
      covariates had nonproportional hazard functions. The study of their time
      dependent effect with the 3-step model confirmed that they were predictive of
      overall survival during the short term follow-up period of 3 months to 2 years.
      However, during the induction period of 0-3 months and the long term follow-up
      period of 2-10 years, there was only 1 independently predictive factor for each
      of these periods: performance status and tumor stage, respectively. CONCLUSIONS:
      The IPI factors are relevant to short term follow-up and permit the selection of
      routine or experimental therapeutic regimens. In contrast, only performance
      status is predictive of a patient's ability to tolerate induction chemotherapy,
      and only tumor stage is predictive of long term survival.

PMID- 9587131
TI  - Hemophagocytic syndrome in five patients with Epstein-Barr virus negative B-cell
      lymphoma.
AB  - BACKGROUND: The recent recognition of the association of Epstein-Barr virus (EBV)
      with T-cell/natural killer cell (T/NK-cell) lymphoma has documented that
      particular types of EBV-containing T/NK-cell lymphoma are frequently complicated
      by hemophagocytic syndrome (HPS). This observation suggests that both EBV and
      proliferating T/NK-lymphoma cells play significant roles in the development of
      HPS. Cytokines released from neoplastic T cells are presumed to account for the
      activation of macrophages, which is followed by a complex cascade of cytokine
      production, resulting in full-blown HPS. Five patients with B-cell lymphoma
      complicated by HPS were studied for elevated serum cytokines, the association of
      EBV, and CD25 expression of lymphoma cells; the aim of this study was to verify
      whether the mechanisms of HPS development hypothesized for T/NK-cell lymphoma
      also operate in B-cell lymphoma. METHODS: Sera were analyzed for the presence of
      inflammatory and immunoregulatory cytokines. Flow cytometry, immunohistology
      (IH), in situ hybridization (ISH), polymerase chain reaction (PCR), and Southern
      blot analysis were performed using bone marrow aspirates, biopsy specimens, and
      autopsy specimens. RESULTS: Immunophenotypic and Southern blot studies verified
      that the lymphoma cells of all five patients were of B-cell lineage. Bone marrow
      aspirates demonstrated histiocytosis with extensive hemophagocytic activity.
      Marked elevation of serum cytokines and expression of CD25 were observed in all
      five patients. However, the results of PCR, ISH using EBER1 probe, and IH for
      latent membrane protein indicated that these lymphoma cells were free of EBV
      infection. CONCLUSIONS: In patients with B-cell lymphoma, EBV infection is not
      necessarily required for the initiation of HPS. In this article, the pathogenesis
      of HPS assumed to be operative in B-cell lymphoma is discussed with reference to
      T/NK-cell lymphoma complicated by HPS.

PMID- 9587132
TI  - Mass screening for neuroblastoma targeting children age 14 months in Sapporo
      City: a preliminary report.
AB  - BACKGROUND: In Sapporo City a mass screening program for neuroblastoma targeting
      children age 6 months (6-MS) was initially introduced in 1981. Since April 1991,
      an additional program has been implemented, aimed at children age 14 months (14
      MS). METHODS: High performance liquid chromatography was employed in the 14-MS.
      Identification of cases was dependent on the Registry of Childhood Malignancies
      in the Hokkaido Prefecture. RESULTS: Of the 85,783 live births in Sapporo City
      during the period 1990-1994, a total of 56,444 participated in the 14-MS
      (compliance rate, 65.8%). By the end of 1996, of 48,448 children who had
      previously taken part in the 6-MS, 6 cases were identified in the 14-MS, and 1
      additional case screened negative but was later diagnosed clinically. Two more
      cases were detected in the 14-MS among the 7996 children who had not participated
      in the 6-MS. Though the incidence of cases identified by the 14-MS was much
      higher than expected, several true-positive cases had unfavorable histology (as
      defined by Shimada's classification), a high dopamine level, and/or a high
      homovanillic acid/vanillylmandelic acid ratio. CONCLUSIONS: Mass screening of
      children age 14 months for neuroblastoma detects cases missed or unscreened at
      age 6 months, though the detection rate appears to be in excess of what would be
      expected from natural incidence.

PMID- 9587133
TI  - The morphologic and molecular genetic categories of posttransplantation
      lymphoproliferative disorders are clinically relevant.
AB  - BACKGROUND: Posttransplantation lymphoproliferative disorders (PT-LPDs) are a
      well-known complication of immunosuppression associated with solid organ
      transplantation. The clinical course of PT-LPDs is unpredictable; some patients
      experience regression of all lesions with a reduction in immunosuppression,
      whereas other patients, despite chemotherapy, radiation therapy, or surgery,
      rapidly die of their disease. In this study, the authors attempted to establish
      whether the previously described morphologic and molecular genetic categories of
      PT-LPD--plasmacytic hyperplasia (PH), polymorphic PT-LPD (polymorphic), and
      malignant lymphoma/multiple myeloma (ML/MM)--are clinically relevant and helpful
      in predicting the clinical outcome of patients who develop these lesions.
      METHODS: To determine the clinical significance of the morphologic and molecular
      genetic categories of PT-LPDs, the clinical characteristics of 32 solid organ
      transplant recipients (26 heart, 5 kidney, and 1 lung), including age, time from
      transplantation to development of PT-LPD, stage of disease, and clinical outcome,
      were compared with the morphologic and molecular genetic features of the 41 PT
      LPDs that they developed (15 PH in 12 patients, 19 polymorphic in 16 patients,
      and 7 ML/MM in 6 patients). Clinical outcome was defined by the following
      categories: 1) regression (after a reduction in immunosuppression) and surgical
      resolution (by surgical excision, with or without a reduction in
      immunosuppression); 2) medical resolution (by chemotherapy and/or radiation
      therapy); and 3) no response. RESULTS: Although there was no difference in the
      time from transplantation to PT-LPD development among patients belonging to the
      three morphologic and molecular genetic categories, there was a significant
      difference in patient age at the time of PT-LPD development (P < 0.0098). Younger
      patients developed PH (mean age of 19 years), whereas older patients developed
      polymorphic PT-LPD (mean age of 35 years) and ML/MM (mean age of 56 years).
      Patients with PH presented with lower stages of disease (Stages I-II) than
      patients with ML/MM (P < 0.0004). Furthermore, there was a statistically
      significant trend between morphologic and molecular genetic category and clinical
      outcome, with decreased likelihood that lesions categorized as PH, polymorphic,
      or ML/MM would regress with a reduction in immunosuppression or be resolved by
      surgery, whereas those classified as ML/MM were more likely to exhibit no
      response to aggressive clinical intervention (P < 0.00006). Furthermore, no
      patients with PH died, whereas 20% with polymorphic PT-LPD and 67% with ML/MM
      died as a direct result of their PT-LPDs. CONCLUSIONS: This study strongly
      suggests that classification of PT-LPDs into the morphologic and molecular
      genetic categories PH, polymorphic, PT-LPD and ML/MM is clinically relevant.

PMID- 9587135
TI  - Essentiality of copper in humans.
AB  - The biochemical basis for the essentiality of copper, the adequacy of the dietary
      copper supply, factors that condition deficiency, and the special conditions of
      copper nutriture in early infancy are reviewed. New biochemical and
      crystallographic evidence define copper as being necessary for structural and
      catalytic properties of cuproenzymes. Mechanisms responsible for the control of
      cuproprotein gene expression are not known in mammals; however, studies using
      yeast as a eukaryote model support the existence of a copper-dependent gene
      regulatory element. Diets in Western countries provide copper below or in the low
      range of the estimated safe and adequate daily dietary intake. Copper deficiency
      is usually the consequence of decreased copper stores at birth, inadequate
      dietary copper intake, poor absorption, elevated requirements induced by rapid
      growth, or increased copper losses. The most frequent clinical manifestations of
      copper deficiency are anemia, neutropenia, and bone abnormalities.
      Recommendations for dietary copper intake and total copper exposure, including
      that from potable water, should consider that copper is an essential nutrient
      with potential toxicity if the load exceeds tolerance. A range of safe intakes
      should be defined for the general population, including a lower safe intake and
      an upper safe intake, to prevent deficiency as well as toxicity for most of the
      population.

PMID- 9587136
TI  - Human whole-body copper metabolism.
AB  - Whole-body copper metabolism is difficult to study in human subjects. However,
      the use of isotopic tracers and kinetics modeling has added a dimension beyond
      what can be learned in humans by direct measurement. Mechanisms regulating total
      body copper seem to be strong, given the relatively small and constant body pool,
      but they are not yet well understood. The efficiency of copper absorption varies
      greatly, depending on dietary intake. Changes in efficiency of absorption help to
      regulate the amount of copper retained by the body. In addition, endogenous
      excretion of copper into the gastrointestinal tract depends heavily on the amount
      of copper absorbed. When dietary copper is high and more is absorbed, endogenous
      excretion increases, protecting against excess accumulation of copper in the
      body. When intake is low, little endogenous copper is excreted, protecting
      against copper depletion. Regulation is not sufficient with very low amounts of
      dietary copper (0.38 mg/d) and appears to be delayed when copper intake is high.
      The use of isotopic tracers and kinetic modeling should aid in elucidating the
      regulatory mechanisms.

PMID- 9587137
TI  - Copper transport.
AB  - In adult humans, the net absorption of dietary copper is approximately 1 mg/d.
      Dietary copper joins some 4-5 mg of endogenous copper flowing into the
      gastrointestinal tract through various digestive juices. Most of this copper
      returns to the circulation and to the tissues (including liver) that formed them.
      Much lower amounts of copper flow into and out of other major parts of the body
      (including heart, skeletal muscle, and brain). Newly absorbed copper is
      transported to body tissues in two phases, borne primarily by plasma protein
      carriers (albumin, transcuprein, and ceruloplasmin). In the first phase, copper
      goes from the intestine to the liver and kidney; in the second phase, copper
      usually goes from the liver (and perhaps also the kidney) to other organs.
      Ceruloplasmin plays a role in this second phase. Alternatively, liver copper can
      also exit via the bile, and in a form that is less easily reabsorbed. Copper is
      also present in and transported by other body fluids, including those bathing the
      brain and central nervous system and surrounding the fetus in the amniotic sac.
      Ceruloplasmin is present in these fluids and may also be involved in copper
      transport there. The concentrations of copper and ceruloplasmin in milk vary with
      lactational stage. Parallel changes occur in ceruloplasmin messenger RNA
      expression in the mammary gland (as determined in pigs). Copper in milk
      ceruloplasmin appears to be particularly available for absorption, at least in
      rats.

PMID- 9587138
TI  - Aceruloplasminemia: an inherited neurodegenerative disease with impairment of
      iron homeostasis.
AB  - Aceruloplasminemia is an autosomal recessive disorder characterized by
      progressive neurodegeneration of the retina and basal ganglia associated with
      specific inherited mutations in the ceruloplasmin gene. Clinical and pathologic
      studies in patients with aceruloplasminemia revealed a marked accumulation of
      iron in affected parenchymal tissues, a finding consistent with early work
      identifying ceruloplasmin as a ferroxidase and with recent findings showing an
      essential role for a homologous copper oxidase in iron metabolism in yeast. The
      presence of neurologic symptoms in aceruloplasminemia is unique among the known
      inherited and acquired disorders of iron metabolism; recent studies revealed an
      essential role for astrocyte-specific expression of ceruloplasmin in iron
      metabolism and neuronal survival in the central nervous system. Recognition of
      aceruloplasminemia provides new insights into the genetic and environmental
      determinants of copper metabolism and has important implications for our
      understanding of the role of copper in human neurodegenerative diseases.

PMID- 9587139
TI  - Mechanisms of copper conservation in organs.
AB  - Organ copper is conserved in response to dietary copper restriction. In organs
      such as brain and heart, conservation is highly efficient, resulting in the loss
      of little organ copper. In contrast, conservation of copper in liver is induced
      only after a significant amount of organ copper is lost. Thus, the conservation
      of copper during dietary restriction is highly organ specific. Although the long
      term pattern of organ copper conservation in rats has now been described through
      use of the continuous feeding of a single stable isotope, the mechanisms
      responsible for this conservation have not been identified or studied. These
      mechanisms may include copper-regulated changes in gene expression as well as
      other mechanisms. We now have the molecular tools that will permit the isolation
      of copper-regulated genes that may play a role in the conservation of organ
      copper. Identification of these mechanisms will allow the exploration of the
      effects of mild short-term and long-term copper deficiency and the role of copper
      in other physiologic and biochemical systems.

PMID- 9587140
TI  - Physiologic function of the Wilson disease gene product, ATP7B.
AB  - The genes responsible for Wilson disease and Menkes syndrome have been cloned and
      identified as copper ATPases. These enzymes form part of a large family of
      transporters, the P-type ATPases. Although copper ATPases share strong structural
      similarities with these other pumps, comparatively little is known about their
      physiologic function. In this review, we examine data relating to the Wilson
      disease protein, ATP7B, in the liver. We present evidence suggesting that ATP7B
      is located intracellularly, together with data suggesting that, at least in part,
      ATP7B may also be found on the canalicular membrane. We also examine the form of
      copper that the transporter recognizes. We then review data on the Long-Evans
      Cinnamon rat, a model for Wilson disease, and discuss what effect the Wilson
      disease mutation has on copper transport. Finally, we conclude that, although we
      have made major advances in our understanding of copper metabolism in the liver,
      there are still many questions awaiting answers.

PMID- 9587141
TI  - Functional analysis of copper homeostasis in cell culture models: a new
      perspective on internal copper transport.
AB  - The movement of copper ions across membrane barriers of vital organs and tissues
      is a priority topic in nutrition and one for which there continues to be little
      understanding of the mechanism. Reports of membrane-bound, copper-transporting
      adenosine triphosphatases (Cu-ATPases) selective for copper ions have brought new
      focus to the problem and prompted fresh ideas. Using a cell culture model
      approach, we attempted to learn whether transport into and out of cells depends
      on a Cu-ATPase. Measurement of transport kinetics in fibroblasts, brain glial
      cells, neuroblastoma cells, and placental cells showed differences in the rates
      of copper uptake and response to sulfhydryl reagents. BeWo cells, a human
      choriocarcinoma placental cell line, behaved as did Menkes fibroblasts by avidly
      absorbing copper but not releasing copper to the immediate environment. Further
      tests showed that BeWo cells did not express the transcript for the membrane
      bound Cu-ATPase that has been identified with Menkes syndrome. Transcript
      induction, however, was achieved by growing BeWo cells on porous filters that
      allowed apical and basolateral surfaces to form. With transcript expression, the
      cells showed a capacity to release copper into the medium. BeWo cells also
      synthesized a form of ceruloplasmin whose structure differed from that of the
      plasma protein and hence may be a product of a different gene. BeWo cells may
      also express the gene for Wilson disease, thus linking Menkes and Wilson proteins
      to maternal delivery of copper. We constructed a model in which both ATPases work
      in concert in a vesicle-based transport mechanism. The vesicle model may help us
      understand the transport of copper across the placenta and all cells in general.

PMID- 9587142
TI  - Copper, lysyl oxidase, and extracellular matrix protein cross-linking.
AB  - Protein-lysine 6-oxidase (lysyl oxidase) is a cuproenzyme that is essential for
      stabilization of extracellular matrixes, specifically the enzymatic cross-linking
      of collagen and elastin. A hypothesis is proposed that links dietary copper
      levels to dynamic and proportional changes in lysyl oxidase activity in
      connective tissue. Although nutritional copper status does not influence the
      accumulation of lysyl oxidase as protein or lysyl oxidase steady state messenger
      RNA concentrations, the direct influence of dietary copper on the functional
      activity of lysyl oxidase is clear. The hypothesis is based on the possibility
      that copper efflux and lysyl oxidase secretion from cells may share a common
      pathway. The change in functional activity is most likely the result of
      posttranslational processing of lysyl oxidase. Copper is essential for organic
      cofactor formation in amine oxidases such as lysyl oxidase. Copper-containing
      amine oxidases have peptidyl 2,4,5 tri(oxo)phenylalanine (TOPA) at their active
      centers. TOPA is formed by copper-catalyzed oxidation of tyrosine, which takes
      place as part of Golgi or trans-Golgi processing. For lysyl oxidase, recent
      evidence (Science 1996;273:1078-84) indicates that as an additional step, a lysyl
      group at the active center of lysyl oxidase reacts with TOPA or its precursor to
      form lysyl tyrosylquinone.

PMID- 9587143
TI  - Effect of copper deficiency on prenatal development and pregnancy outcome.
AB  - Copper deficiency during embryonic and fetal development can result in numerous
      gross structural and biochemical abnormalities. Such a deficiency can arise
      through a variety of mechanisms, including low maternal dietary copper intake,
      disease-induced or drug-induced changes in maternal and conceptus copper
      metabolism, or both. These issues are discussed in this article along with the
      use of in vitro embryo culture models to study the mechanisms underlying copper
      deficiency-induced teratogenesis. Current data suggest that changes in free
      radical defense mechanisms, connective tissue metabolism, and energy production
      can all contribute to the dysmorphogenesis associated with developmental copper
      deficiency.

PMID- 9587144
TI  - Clinical manifestations of nutritional copper deficiency in infants and children.
AB  - A series of reports in the 1960s highlighted nutritional copper deficiencies in
      infants and children recovering from malnutrition in Peru; since that time, a
      cascade of additional cases in premature infants, in patients receiving total
      parenteral nutrition, and in those receiving special diets or unmodified cow milk
      have been reported. The identification by Danks that Menkes syndrome, a
      genetically determined defect in copper absorption and utilization, is
      responsible for the observed clinical manifestations provided further insight
      into the physiopathologic effects of copper deficiency. New information on the
      metabolism and physiologic role of copper, plus the identification of additional
      copper metalloenzymes and improvement in how to determine copper status, has
      fueled interpretation and speculation on how and why the classic signs of copper
      deficiency occur, as well as on the possible effects of mild deficiencies. Also
      under scrutiny are potential interactions between other elements and the effects
      of other elements, even when given in acceptable amounts, on copper status. There
      should be no constraints in thinking on other possible effects of impaired copper
      status in humans. I review some of the history of nutritional copper deficiency
      in infants and children and attempt to interpret some of the clinical
      manifestations in light of newly acquired information.

PMID- 9587145
TI  - Clinical conditions altering copper metabolism in humans.
AB  - Overt copper deficiency is not believed to be a widespread public health concern
      for most population groups. However, a variety of case studies suggest that under
      certain circumstances, clinical conditions may predispose individuals to the risk
      of copper deficiency or copper excess. Acquired copper deficiency has been
      documented in conditions predisposing to inadequate copper intakes, in
      prematurity, in malabsorption syndromes, and in conditions predisposing to
      excessive copper losses. In contrast, increases in copper concentrations have
      been reported in response to stress, inflammation, and infection; in Parkinson
      disease and diabetes mellitus; and in conditions involving an obstruction to bile
      flow.

PMID- 9587146
TI  - Menkes syndrome and animal models.
AB  - Menkes syndrome is an X-linked genetic copper deficiency that is usually fatal in
      early childhood. Milder variants exist, including occipital horn syndrome, which
      is primarily a connective tissue disorder. Mutations of the mottled locus in mice
      produce a wide range of copper-deficient phenotypes that are good models for
      human diseases. Understanding the nature of the defects has been greatly
      increased as a result of the identification of the gene affected in Menkes
      syndrome. The gene spans approximately 140 kilobases, contains 23 exons, and
      encodes a copper-transporting ATPase termed MNK that is thought to be involved in
      copper efflux from cells. More recent studies show that MNK is located primarily
      in the trans-Golgi compartment of Chinese hamster ovary cells. Copper-resistant
      cells overexpress MNK and can efflux more copper than parental cells, consistent
      with the copper efflux role proposed for MNK. Patients with Menkes syndrome are
      predicted to have little or no MNK activity, whereas patients with occipital horn
      syndrome have less severe mutations and some residual MNK activity is predicted.
      Similarly, the mottled mice mutants have a range of mutations in the MNK gene
      homologue. Complete loss of MNK, however, produces a fetal lethal phenotype in
      mice. A model is proposed to explain the wide range of phenotypes exhibited by
      the different mouse mutants. Further research into the cell biology of copper
      transport is expected to reveal more about the molecular basis of copper
      homeostasis.

PMID- 9587147
TI  - Diagnosis and therapy of Menkes syndrome, a genetic form of copper deficiency.
AB  - In the 25 y since copper deficiency was first delineated in persons with Menkes
      syndrome, advances in our understanding of the clinical, biochemical, and
      molecular aspects of this rare disorder have surpassed progress in the design of
      effective therapies. In contrast with purely nutritional copper deficiency, in
      which copper replacement can be curative, the nature of the basic defect in
      Menkes syndrome suggests that corrective efforts are likely to be more
      complicated, a point supported by the cumulative literature on this topic as well
      as by emerging molecular data. In this paper, certain clinical, biochemical, and
      molecular aspects of copper histidine treatment in 25 Menkes syndrome patients at
      the National Institutes of Health are reviewed. The delineation of a distinctive
      neurochemical pattern in plasma and cerebrospinal fluid, reflecting deficiency of
      the copper enzyme dopamine beta-monooxygenase, is arguably the most important
      finding in the study of Menkes syndrome. This abnormal pattern has proven
      extremely reliable as a rapid diagnostic test, enabling early identification of
      affected infants--a fundamental requirement for improving clinical outcomes. Of
      11 patients identified by prenatal or prompt postnatal testing and treated within
      the first 10 d of age, one walked at 14 mo of age and has normal neurodevelopment
      at age 3 y and another infant's early progress appears promising. However, five
      patients died in infancy and neurodevelopmental outcome was suboptimal in four
      others. Consideration of additional therapeutic strategies seems necessary,
      therefore, for most patients and families facing this troublesome form of copper
      deficiency.

PMID- 9587148
TI  - Copper, iron, zinc, and manganese in dietary supplements, infant formulas, and
      ready-to-eat breakfast cereals.
AB  - High intakes of iron, zinc, or manganese can interfere with copper absorption.
      Thus, the purpose of this study was to determine whether the amounts and chemical
      forms of iron, zinc, manganese, and copper added to food products and nutritional
      supplements might pose a threat to copper status. More than 25% of the vitamin
      and mineral supplements examined contained no copper, 40% contained the poorly
      absorbed cupric oxide, and < 30% contained a highly bioavailable form of copper
      such as cupric sulfate or cupric chloride. Nearly 40% of the prenatal supplements
      examined contained both iron and zinc without a nutritionally significant amount
      of copper. More than 80% of the infant formulas examined had ratios of iron to
      copper exceeding 20:1, which is higher than the recommended ratios of 10-17:1.
      None of the 40 ready-to-eat breakfast cereals examined were fortified with copper
      or manganese although 50% of these cereals contained > or = 25% of the reference
      daily intake for both iron and zinc. Copper availability could be improved by
      reformulation of several food products and supplements.

PMID- 9587149
TI  - Copper intake and assessment of copper status.
AB  - The diagnosis of marginal copper deficiency has not been perfected despite an
      increased understanding of the physiologic roles of copper. The use of
      nonstandardized procedures and the effects of factors other than copper nutriture
      have impeded identification of an ideal indicator of copper nutritional status in
      humans. A review of studies of experimental copper deprivation conducted in adult
      humans over the past 12 y indicated that between 1.0 and 1.25 mg Cu/d is needed
      by adults for copper maintenance for periods of up to 6 mo and that < or = 2.6 mg
      Cu/d for periods of up to 42 d is not sufficient for recovery from copper
      deprivation. Copper-containing enzymes in blood cells, such as erythrocyte
      superoxide dismutase and platelet cytochrome-c oxidase, may be better indicators
      of metabolically active copper and copper stores than plasma concentrations of
      copper or ceruloplasmin because the enzyme activities are sensitive to changes in
      copper stores and are not as sensitive to factors not related to copper
      nutriture.

PMID- 9587150
TI  - Copper nutrition during infancy and childhood.
AB  - Full-term human infants are believed to possess adequate copper stores to last
      through weaning regardless of the copper content of the diet they are fed. This
      may not be generally true, however; a combination of low copper intake and low
      bioavailability from the diet may lead to copper deficiency. More information is
      needed on the bioavailability of copper from different infant diets, but it
      appears that copper is well absorbed from breast milk compared with infant
      formula. Several dietary factors that may affect copper absorption in infants,
      such as protein sources, amino acids, phytate, ascorbic acid, and other essential
      cations, need to be evaluated further. Studies in human infants evaluating these
      factors through use of stable isotope methods, as well as better indicators of
      copper status, are needed before the copper requirements of infants can be
      established. This is particularly important for premature infants who, born with
      inadequate copper stores, are prone to develop copper deficiency unless given
      higher provisions of copper. The possibility of copper excess also needs to be
      considered because there are limited opportunities to diagnose copper toxicity.
      Finally, the role of homeostatic regulation of copper metabolism in infants needs
      to be evaluated.

PMID- 9587151
TI  - Copper absorption and bioavailability.
AB  - The human gastrointestinal system can absorb 30-40% of ingested copper from the
      typical diets consumed in industrialized countries. Experimental data support the
      existence of a carrier-mediated transport mechanism with an affinity constant in
      the micromolar range. Aging probably decreases the efficiency of copper
      homeostasis, resulting in higher plasma copper concentrations in the elderly.
      Physiologic differences may account for the higher cupremia of females.
      Supplements of minerals with similar chemical characteristics could reduce copper
      absorption. This property has pharmacologic applications in Wilson disease.
      Manipulation of the fiber content of the diet may have an indirect effect on
      copper bioavailability by altering the bioavailability of mineral antagonists.
      Proteins and soluble carbohydrates tend to improve copper absorption and
      bioavailability by enhancing its solubility and intestinal bulk flow. Organic
      acids, other than ascorbic acid, or agents that form low-molecular-weight
      chelates, are likely to have a positive effect on overall copper absorption.
      Conditions associated with malabsorption of macronutrients and gastrointestinal
      disease can impair copper uptake and contribute to suboptimal copper status.

PMID- 9587152
TI  - Adaptation to high and low copper intakes: its relevance to estimated safe and
      adequate daily dietary intakes.
AB  - Different approaches are used to determine ideal ranges of intakes and threshold
      levels of safe intakes for nutrients. A consequence of this is that, for
      inorganic nutrients particularly, a safe level set by traditional toxicologic
      procedures might be compromised because it is inconsistent with physiologic
      observations and customary intakes and because the levels set may allow an
      inordinately narrow range of safe intakes above the upper limit of recommended
      intakes. This article used data from studies in animal models and in human
      volunteers to construct a provisional continuum of adaptive processes and
      pathophysiologic phenomena associated with a range of copper intakes extending
      from toxic to deficient to suggest an approach to establishing an acceptable
      range of intakes for copper that would address simultaneously the advisory and
      regulatory needs of nutritionists and toxicologists.

PMID- 9587153
TI  - Copper and immunity.
AB  - The immune system requires copper to perform several functions, of which little
      is known about the direct mechanism of action. Animal models and cells in culture
      have been used to assess copper's role in the immune response. Some of the recent
      research showed that interleukin 2 is reduced in copper deficiency and is likely
      the mechanism by which T cell proliferation is reduced. These results were
      extended to show that even in marginal deficiency, when common indexes of copper
      are not affected by the diet, the proliferative response and interleukin
      concentrations are reduced. The number of neutrophils in human peripheral blood
      is reduced in cases of severe copper deficiency. Not only are they reduced in
      number, but their ability to generate superoxide anion and kill ingested
      microorganisms is also reduced in both overt and marginal copper deficiency. This
      mechanism is not yet understood. Neutrophil-like HL-60 cells accumulate copper as
      they differentiate into a more mature cell population and this accumulation is
      not reflected by increases in Cu/Zn superoxide dismutase or cytochrome-c oxidase
      activities. The identity of copper-binding proteins in this cell type may be
      useful in learning new functions of copper or assessing copper status.
      Neutrophils, because they are short-lived and homogeneous cell populations, are
      predicted to be an effective and valuable tool for assessing nutrient status in
      human populations.

PMID- 9587154
TI  - Manifestations of copper excess.
AB  - Although copper is an essential micronutrient normally subject to effective
      homeostatic control, excess dietary intakes can in some circumstances be toxic.
      Susceptibility to copper toxicosis depends, however, on many factors, including
      species, genetics, age, and diet. This appears to reflect not only variations in
      the efficiency of the absorption and excretion of copper but also differences in
      the intake of other hepatotoxic or protective factors, differences in the
      cellular distribution of copper, and differences in the expression of specific
      copper transport and storage proteins. Many of the toxic effects of copper, such
      as increased lipid peroxidation in cell membranes and DNA damage, are related to
      its role in the generation of oxygen free radicals.

PMID- 9587155
TI  - Role of copper in Indian childhood cirrhosis.
AB  - Of the cirrhoses that affect Indian children, Indian childhood cirrhosis (ICC) is
      a discrete clinical and histologic entity in which large amounts of copper are
      deposited in the liver. The evidence linking copper deposition to increased
      dietary copper intake in infancy was reviewed. Prevention of this feeding pattern
      prevents ICC, and the disease has now largely disappeared from many parts of
      India. Penicillamine, if given before the terminal clinical stage of ICC, reduces
      mortality from 92% to 53%. Long-term survivors show a sequence of histologic
      resolution, resulting either in inactive micronodular cirrhosis or in virtually
      normal histologic appearance. Twenty-nine treated ICC patients reexamined at 8.8
      y of age (range: 6.3-13 y), 5-12 y after diagnosis, were well and had normal
      results from liver function tests. Clinical and epidemiologic evidence show that
      there must be excessive copper ingestion for ICC to develop, but the lack of an
      animal model, the inconstant relation between liver copper concentrations and
      liver damage, and the rarity of liver disease in adults suggests that other
      etiologic factors contribute. Two mechanisms are discussed: 1) that copper may be
      acting in synergy with a hepatotoxin, or 2) that there may be a genetic
      predisposition to copper-associated liver damage, as suggested recently for
      Tyrollean childhood cirrhosis. Although ICC is now rare, sporadic cases of an ICC
      like disorder in infants continue to occur. There should be a greater awareness
      among pediatricians of this disease to enable early diagnosis. Penicillamine
      should be used early and adverse prognostic factors recognized as indications for
      early transplantation and unregulated water supplies should not be used to
      prepare infant feeds.

PMID- 9587156
TI  - Idiopathic copper toxicosis.
AB  - Liver diseases of infancy and childhood are generally rare and within the
      spectrum of these disorders, only a few subtypes are related to abnormal hepatic
      copper accumulation. Idiopathic copper toxicosis has been defined as such a
      subtype; although this disease is characterized by distinct clinical and
      pathologic features, its exact etiology is still controversial. On the basis of a
      review of the literature, supplemented by our own observations of 138 cases
      endemic to western Austria, we hypothesize that idiopathic copper toxicosis is
      caused by a synergy of an autosomal-recessive inherited defect in copper
      metabolism and excess dietary copper. Increased awareness of the disease should
      enable early diagnosis and lead to successful treatment, thereby improving the
      overall poor prognosis of affected patients.

PMID- 9587157
TI  - Wilson disease and canine copper toxicosis.
AB  - In this article we review the current clinical and research status of Wilson
      disease and canine copper toxicosis. One of the main clinical challenges in
      Wilson disease is for clinicians to recognize the possibility of Wilson disease
      when young patients present with liver disease, psychiatric disease, or a
      movement-disorder type of neurologic disease. Once the possibility of the disease
      is recognized, many copper-related tests are available that are quite accurate in
      making the diagnosis or ruling it out. It is important to remember that this is
      an inherited disease and that family members at risk should be screened,
      particularly siblings. The cloning of the Wilson disease gene opened up the
      possibility that a direct DNA test could be developed, allowing convenient
      screening of certain patients and family members. However, the large number of
      mutations already found, with no small set of mutations dominating the picture,
      have thwarted this approach. Once the diagnosis has been made, a variety of
      treatments are available. For maintenance therapy, therapy of presymptomatic
      patients, and therapy of pregnant patients, we use zinc. For initial therapy of
      patients with liver disease, we use a combination of zinc and trientine. For
      initial therapy of patients with neurologic disease we use tetrathiomolybdate.
      Canine copper toxicosis in Bedlington terriers is due to a gene different from
      the gene for Wilson disease. However, the disease is treatable with the same
      array of anticopper therapies that work in humans. Recently, we established
      linkage of the copper toxicosis gene to a microsatellite marker, which has made
      available a linkage test to breeders of Bedlington terriers.

PMID- 9587158
TI  - Mechanisms for protection against copper toxicity.
AB  - Essential transition metals such as copper, molybdenum, and zinc and nonessential
      metals like cadmium, mercury, and lead can be toxic at the cellular, tissue, and
      organ levels when present in excess. To avoid metal-induced toxicity most
      organisms use a redundant combination of metal-regulated import inhibition,
      sequestration, and enhanced export mechanisms. Combinations of these mechanisms
      are used to form detoxification pathways controlled through metal-binding
      proteins at transcriptional, translational, or enzymatic levels. In mammalian
      pathways copper is partially detoxified by sequestration in the metal-binding
      metallothioneins or export via the copper-translocating ATPases. Copper
      regulation of these two mechanisms is afforded by specific conformational changes
      induced in regulatory proteins on metal binding.

PMID- 9587159
TI  - Safety guidelines for copper in water.
AB  - It is important for public health authorities to set a scientifically sound
      guideline value for the safe ingestion of copper in drinking water. To date, the
      principal health-based guideline values have been set by the US Environmental
      Protection Agency (1.3 mg Cu/L) and the World Health Organization (2.0 mg Cu/L).
      However, close examination of the data and assumptions used in the derivation of
      these values reveals a paucity of scientifically defensible information. Several
      international groups are now reviewing this issue, and others have begun
      epidemiologic studies that may provide useful copper exposure and toxicity data.
      Investigations of acute copper toxicity in human populations are most likely to
      affect future revisions of the guideline value for copper in drinking water.

PMID- 9587160
TI  - 17 beta-Oestradiol and 1 alpha,25-dihydroxycholecalciferol modulate constitutive
      and bone matrix-induced interleukin-1 beta (IL-1 beta) production by peripheral
      blood mononuclear cells isolated from postmenopausal women.
AB  - Local production and release of interleukin-1 (IL-1) may be of importance for
      bone remodeling, since this cytokine is known to stimulate bone resorption. We
      have studied the effect of bone matrix constituents on IL-1 beta production by
      peripheral blood mononuclear cells (PBMCs) isolated from 20 postmenopausal non
      osteoporotic women. Hydroxyapatite (0.5 mg/ml) and heat-denaturated collagen (25
      micrograms/ml) stimulated IL-1 beta production 5-fold and 520-fold, respectively,
      compared to control (p < 0.01). In contrast, transforming growth factor-beta (TGF
      beta, 10 ng/ml), a cytokine which is abundant in bone matrix, suppressed median
      IL-1 beta release to 13% of control value (p < 0.01). The bone matrix-induced
      changes in IL-1 beta production were modulated by 10 nmol/1 17 beta-oestradiol
      and 10 nmol/1 1 alpha,25-dihydroxy-cholecalciferol (1,25(OH)2D3). Specifically,
      17 beta oestradiol stimulated constitutive IL-1 beta release with 89% (p < 0.01)
      and nullified the suppressive effect of TGF-beta. Moreover, 1,25(OH)2D3 had a
      synergistically stimulatory effect with both hydroxyapatite and collagen,
      although there was no effect of this hormone when added alone. The adherent cells
      were slightly more elongated after treatment with 1,25(OH)2D3 and collagen, while
      TGF-beta and 17 beta-oestradiol had no effect on cellular morphology. Addition of
      hydroxyapatite resulted in long and spindle-shaped cells, and phagocytosis of the
      particles occurred. The modulatory effects of oestrogen and vitamin D on
      constitutive and bone-matrix induced IL-1 beta production by PBMCs may be of
      importance for bone remodelling during postmenopausal bone loss and at a site of
      fracture.

PMID- 9587161
TI  - Thyroid function in postmenopausal breast cancer patients treated with tamoxifen.
AB  - Thyroid function was evaluation in 26 postmenopausal women with breast cancer
      before and at various time intervals during treatment with tamoxifen. Tamoxifen
      treatment suppressed plasma levels of FT3 and FT4 (p < 0.005 for both) and
      elevated plasma concentrations of TBG (p < 0.005 and TG (p < 0.025). In general,
      these changes became significant after 6 months of treatment. Plasma TSH
      increased significantly after 1 y of treatment (p < 0.025). A fall in FT4 and FT3
      combined with increase in TSH suggests a reduced bioavailability of T4 and T3
      during tamoxifen treatment. The increase in TG may reflect a reduced synthesis or
      liberation of T4 resulting in a reduced plasma level of FT4. Our findings suggest
      that tamoxifen influences the thyroid hormone levels, not only by modulating
      plasma TBG, but also by interfering with hormone synthesis or secretion in the
      thyroid gland.

PMID- 9587162
TI  - Prostaglandin E1 in peripheral vascular disease: a PET study of muscular blood
      flow.
AB  - BACKGROUND: Increase of blood flow in the ischaemic leg is believed to represent
      the main action of prostaglandin E1 (PGE1) in the therapy of peripheral vascular
      disease (PVD). There is no reliable data in man concerning the amount of increase
      in muscular blood flow (MBF) of the calf, and the difference between intra
      arterial and intravenous application. PATIENTS AND METHODS: We conducted a
      positron emission tomography (PET) study of MBF with 15O-water as flow tracer.
      Fifteen patients with PVD and three healthy volunteers were given 5 micrograms
      PGE1 intra-arterially over 50 min; PET scans were taken at 0, 25 and 50 min.
      Additionally, eight of the patients were investigated during an intravenous
      infusion of 40 micrograms PGE1 over 120 min; PET scans were taken at 0, 30, 60
      and 120 min. RESULTS: Increase of muscular blood flow by intra-arterial PGE1
      averaged 80%. A steal phenomenon was not observed. The amount of flow enhancement
      depended on whether or not the femoral artery was patent. During intravenous
      PGE1, muscular blood flow remained unchanged. CONCLUSIONS: In man, the
      pharmacodynamic profile of intra-arterial PGE1 differs clearly from intravenous
      PGE1. The flow-enhancing property is lost during metabolization in the lung.
      Since no difference exists between the therapeutic efficacy of intraarterial and
      intravenous PGE1, the impact on muscular blood flow is not as important as
      suggested previously.

PMID- 9587163
TI  - Beneficial effect of captopril against ischaemia-reperfusion injury in isolated
      guinea pig hearts.
AB  - The study was designed to clarify whether captopril, an angiotensin-coverting
      enzyme inhibitor, will reduce the injury of global ischaemia and reperfusion
      after cardioplegic arrest in isolated guinea pig hearts, in a modified
      Langendorff model. The hearts were randomly allocated into four groups (n = 10 in
      each) and subjected to 90 min of normothermic global ischemia, followed by 30 min
      of reperfusion; in all groups, cardioplegic arrest was achieved by administering
      St. Thomas's Hospital cardioplegic solution (STHCS). The first group was utilized
      as the control group. In the second group, captopril (200 mumol/L) was added to
      STHCS. In the third group, oral pretreatment was carried out (0.3 mg/kg captopril
      was given twice a day for 10 days). In the fourth group, oral pretreatment was
      achieved and captopril-enriched solution was applied in the first 5 min of
      reperfusion. Although the study groups showed better recovery of contractility
      than the control group, in the fourth group the hearts had the best left
      ventricular contractile function, where contractile force (g contractility/g
      heart weight) was 55.4% +/- 3.8% of the preischameic values. Groups I, II, and
      III achieved 31.0% +/- 3.2%, 41.6% +/- 3.8%, and 48.3% +/- 3.9% of their
      preischaemic contractile force values. Creatine kinase leakage was significantly
      lower and postischaemic coronary flows, too, were significantly higher in the
      fourth group. Coronary flow after reperfusion increased from 48.5 +/- 6.7 to 65.2
      +/- 7.1 ml/min g heart in group 4 (p < 0.05). Myocardial lipid peroxides and
      glutathione contents showed that there was a correlation between the depletion of
      myocardial glutathione content and increased lipid peroxidation. These
      preliminary results showed that: the addition of captopril to reperfusion
      solution and oral preconditioning improved post-ischameic myocardial function and
      decreased myocardial injury.

PMID- 9587164
TI  - Evaluation of an ionized magnesium-pH analyzer--NOVA 8.
AB  - An ion-selective analyzer (NOVA 8 [previously NOVA CRT], NOVA Biomedical Waltham,
      USA) for simultaneous measurement of the concentration of ionized magnesium
      (cMG2+) and pH is investigated for linearity and influence of calcium ions on the
      Mg2+ results in different Mg2+ aqueous solutions with/without added calcium.
      Within the cMg2+ range 0-3.0 mmol/L, which covers most clinical values, we found
      cMg2+ values close to the line of identity, with a sensitivity about 94%, but
      0.09 mmol/L lower in the absence of Ca2+. The analytical precision (CV) for human
      serum control was 1.7% in the physiological range. The accuracy and precision
      data for the Mg2+ electrode meet the demands for reliable results within the
      range for clinical use. We found a reference interval (95%) for cMg2+ of between
      0.43 and 0.59 mmol/L serum, with a mean value of 0.51 mmol/L for healthy adults
      in the non-fasting state with no relation to sex or age. The mean cMg2+ was 61%
      of the mean concentration of plasma total magnesium (cTMg) ranging from (95%) 49%
      to 73%. No significant correlation was found between cMg2+ and total protein,
      albumin, phosphate, Ca2+, and total CO2. No significant difference was found
      between mean values for cMg2+ in whole blood, plasma, and serum. Serum samples
      could be stored for 24 h at 4 degrees C without significant change. Storage at 
      20 degrees C for 7 months caused a mean cMg2+ decrease of 8.3%. The mean slope
      delta lgcMg2+/delta pH measured after equilibration with different pCO2 values in
      each serum sample from the reference population was -0.0110, indicating a close
      agreement between the values for actual cMg2+ and adjusted cMg2+ (pH = 7.4).

PMID- 9587165
TI  - Serum cholesterol and haematology at age eight to ten years.
AB  - The aim of the study was to estimate 95% reference ranges for blood constituents
      in 9-year-old children. Venepuncture was successful in 753 white children age 8-9
      years in 21 areas in England and 5 in Scotland. Agreement with published
      reference ranges for haematological measurements from undocumented samples was
      good. The reference ranges were 3.22 to 5.79 mmol/l for serum total cholesterol,
      0.9 to 2.1 mmol/l for high density lipoprotein cholesterol, and 13 to 61
      micrograms/l for ferritin. The upper limit for total cholesterol is well above
      the recommended level for adults, with 9.3% of children having a value of 5.2
      mmol/l or more. The results provide a scientific basis for ranges previously
      published for haematological measurements. Documented data should be combined
      from national studies to provide further reference ranges for routine use.

PMID- 9587166
TI  - High-affinity choline uptake under various pH conditions: investigation of
      synaptosomal fluorescence.
AB  - The choline transport into synaptosomes obtained from the rat brain striatum was
      studied in the presence and absence of Na+ ions within the pH range 3.9-9.1. The
      intrinsic tryptophan fluorescence was investigated in synaptosomes at varying pH.
      Three pH ranges with different interpositions of the Na(+)-dependent and Na(+)
      independent uptake curves were revealed: acid, alkaline, and weak-acid regions.
      It is assumed that pH 6-7 may be important in regulation of the cholinergic
      function because of the complicated interpositions of the two curves. The Km and
      Vmax values of both the Na(+)-dependent and Na(+)-independent processes for the
      striatal fraction were calculated using Lineweaver-Burk plots at three pH values.
      Some differences in the intrinsic tryptophan fluorescence of the synaptosomal
      membrane were observed in the presence and absence of Na+ ions in the pH range 6
      7, but they were not statistically significant. At the variations of pH the
      alterations in the choline transport system did not correspond to the total
      structural changes in the synaptosomal membrane, when monitored by intrinsic
      tryptophan fluorescence. The pH-evoked choline transport changes may be due to
      specific alterations in the choline transport-related proteins.

PMID- 9587167
TI  - Administration of a small amount of lard enhances intimal thickening in the
      balloon catheter injury model without affecting serum lipids.
AB  - Effects of fatty acids on intimal thickening induced by a balloon catheter injury
      model were investigated by feeding rabbits a small amount of either lard [L] or
      fish oil [F]. Serum lipids of these groups were not different from those of basal
      diet-fed rabbits [controls] after 4 weeks of feeding. Serum saturated fatty acids
      such as 14:0, 16:0, and 18.0 were significantly greater in the L-fed rabbits
      compared with controls, but those of the aorta were not significantly different.
      Fatty acid composition of the F-fed rabbits was only different from that of the
      controls in that n-3 fatty acids slightly increased. The mean and maximum intimal
      thickening 2 weeks after ballooning, carried out 2 weeks after feeding, were
      significantly higher in the carotid arteries of the L-fed rabbits than in the
      controls. The intimal thickening of the F-fed rabbits did not significantly
      differ from that of the controls. These results suggest that lard promotes the
      formation of the smooth muscle cell dominant type of arteriosclerosis without
      affecting serum lipid levels.

PMID- 9587168
TI  - Determination of low levels of total mercury in blood and plasma by cold vapour
      atomic fluorescence spectrometry.
AB  - A sensitive and semi-automated analytical method allowing determination of low
      and normal levels of total mercury in human blood and plasma using cold vapour
      atomic fluorescence is described. Samples are digested overnight, or at an
      elevated temperature for 4 h, followed by bromination at room temperature. After
      reduction with tin (II), analysis is performed using automated continuous flow
      vapour generation coupled to a fluorescence detector, allowing 20 samples to be
      analysed per hour. Detection limits for blood and plasma were found to be 0.9 and
      0.5 nmol Hg l-1, respectively. The method precision at various concentrations of
      mercury was determined. For whole blood at 8.1 nmol Hg l-1 and 12.9 nmol Hg l-1,
      the within-day precision was 5% and 6% and the between-day precision 9% and 6%,
      respectively. For plasma at 1.3 nmol Hg l-1, the within-day precision was 13%
      while the between-day precision was 17%. Accuracy was evaluated by an inter
      laboratory comparison study. At blood mercury concentrations below 60 nmol Hg l-1
      the results from the current method were almost identical to those obtained with
      radiochemical neutron activation analysis, commonly regarded as a reference
      method. The present method should have merits in relation to previously used
      methods using atomic absorption spectrometry.

PMID- 9587169
TI  - Blood-free magnesium concentration declines following graded experimental
      traumatic brain injury.
AB  - Traumatic brain injury has been shown to result in a decrease in brain-free
      magnesium concentration that is associated with the development of neurologic
      motor deficits. Although these changes have been well characterized in the brain,
      changes in free magnesium homeostasis have not been characterized in other fluid
      compartments. The current experiments use ion selective electrodes to measure
      alterations in blood-free magnesium concentration following graded experimental
      brain injury in rats and to compare these changes with subsequent neurologic
      outcome. After severe impact-acceleration-induced injury, blood-free magnesium
      levels significantly declined (p < 0.05) by 25% and remained depressed for at
      least 4 days after injury. After moderate injury, the decline in blood-free
      magnesium was less than that observed in the severe injury group with respect to
      both degree of decline and duration of decline. The post-traumatic blood-free
      magnesium concentration correlated to observed motor deficits as assessed by
      rotarod evaluation (p < 0.001). We conclude that blood-free magnesium levels may
      be a prognostic indicator of outcome following severe traumatic brain injury.

PMID- 9587170
TI  - Analytical aspects of the automated CKMB1,2 and CKMM1,2,3 isoform determination
      and its relation to other biochemical markers.
AB  - The automated (CK)MB1,2/MM1,2,3 isoform measurement, based on electrophoresis,
      has been simplified to the point that it has become possible to perform this
      analysis on a 24-h routine basis. We studied analytical aspects of this analysis
      and its clinical relevance in relation to other biochemical markers (CK total,
      CKMB activity, CKMB mass, myoglobin, Troponin I and Troponin T) in patients with
      acute myocardial infarction (AMI), patients with unstable angina pectoris (UAP),
      and healthy donors. Furthermore, the additional significance of the analysis was
      evaluated in patients with clinically unexpected, raised CKMB/CK total
      activities. The storage of serum at 4 degrees C does not influence the MB2/MB1
      ratios, whereas storage at 20 degrees C changes them significantly. MM3/MM1 and
      normal MB2/MB1 ratios show lower coefficients of variation than increased MB2/MB1
      ratios. Between 2 and 30 h after myocardial tissue damage, AMI patients showed a
      characteristic change in CK isoform patterns. At a mean time of 3.6 h after the
      onset of symptoms we found raised MB2/MB1 ratios in 94% of these patients. With
      the information of the CK isoform analysis unexpected abnormal CK activities
      could explained by CK macro enzymes (Ig-bound and mitochondrial), insufficient CK
      clearance capacity, enzyme activities 4 h after (re-)infarction and raised CK
      activity 15 h after skeletal muscle damage. We conclude that the CK isoforms are
      relatively simply to assess; they are adequate tools with which to indicate the
      CK kinetics over a period lasting between 2 and 30 h after tissue damage with a
      single blood sample and a single analysis; the CK isoform analysis has additional
      value in explaining inappropriate CKMB/CK total activities, and the MB2/MB1
      ratios show to be one of the best early parameters for discriminating patients
      with AMI on admission to hospital.

PMID- 9587171
TI  - A pilot study of the prevalence of chlamydial infection in a national household
      survey.
AB  - BACKGROUND: The prevalence of Chlamydia trachomatis genital infection in the
      United States population is unknown. Using a new urine test for C. trachomatis,
      we conducted a pilot survey as part of the National Health and Nutrition
      Examination Survey III (NHANES III). GOAL: To determine whether the prevalence of
      chlamydial infection in a convenience sample of NHANES participants was high
      enough to justify testing for C. trachomatis in a national survey. STUDY DESIGN:
      NHANES III, conducted from 1988 to 1994, was based on a stratified multistage
      probability sample of the United States population. Non-Hispanic blacks and
      Mexican-Americans were oversampled. Using the ligase chain reaction assay for C.
      trachomatis, we tested urine from participants 12 to 39 years of age from 10 of
      the 89 sites of NHANES III. The prevalence of infection was calculated by racial
      or ethnic group. RESULTS: We tested 1,144 study participants, of whom 65% were
      female, 30% were non-Hispanic blacks, and 30% were Mexican-American. Prevalence
      was higher for non-Hispanic blacks (7%) than for Mexican-Americans (3%) and non
      Hispanic whites (2%). Prevalence was higher for women than men in non-Hispanic
      blacks (7% vs. 6%), Mexican-Americans (5% vs. 2%), and non-Hispanic whites (2%
      vs. 1%). In 15- to 19-year-old women, prevalence was 13% in non-Hispanic blacks,
      11% in Mexican-Americans, and 5% in non-Hispanic whites. CONCLUSION: The
      prevalence of C. trachomatis genital infection was high enough to suggest that a
      reliable national prevalence estimate could be obtained in a national probability
      sample survey.

PMID- 9587172
TI  - Chlamydia trachomatis: the more you look, the more you find--how much is there?

PMID- 9587173
TI  - Heterosexual repertoire is associated with same-sex experience.
AB  - OBJECTIVE: The association of sexual repertoire with sexual preference,
      partnership and sociodemographic characteristics, and sexual history among white
      American (WA) and African-Americans (AA) is described. DESIGN: Cross-sectional
      computer-assisted telephone survey. METHODS: Seattle residents 18 to 39 years of
      age selected via random digit dialing; an additional sample of AA sampled from
      listed telephone numbers from census tracks with over 40% Aa. RESULTS: The study
      included 356 WA and 140 AA ever engaging in vaginal intercourse who answered
      questions regarding their usual sexual repertoire with their most recent opposite
      sex partner. The 5% of WA engaging in vaginal, oral, and anal intercourse with
      their most recent opposite-sex partner were 2.7 times (95% CI: 0.9, 7.9) as
      likely to report nonmonogamy and 8.4 times (95% CI: 2.6, 27.2) as likely to
      report a history of same-sex partners. Persons reporting a history of both same-
      and opposite-sex partnerships were more likely than those with only opposite-sex
      partners to report engaging in anal and oral sex with their most recent opposite
      sex partner regardless of gender (anal: women 24% vs. 4%, p < 0.001; men: 33% vs.
      6%, p < 0.001; oral: women 95% vs. 74%, p = 0.03; men 89% vs. 78%, p = 0.4).
      Persons with a history of a same-sex partner were also more likely than those
      with only opposite-sex partners to have a nonmonogamous current relationship (WA:
      odds ratio [OR] = 2.3; 95% CI: 0.9, 5.7; AA: OR = 6.8; 95% CI: 0.6, 338) to
      engage in sex during menses (WA: OR = 1.9; 0.7, 5.4; AA: 9.6; 1.0, 4.6) and to
      have more sex partners in their life (WA: p = 0.002; AA: p = 0.07). CONCLUSIONS:
      Diverse sexual repertoires are associated with other risk behaviors putting the
      individual at high risk of acquiring or transmitting a sexually transmitted
      diseases (STD).

PMID- 9587174
TI  - A serosurvey of Haemophilus ducreyi, syphilis, and herpes simplex virus type 2
      and their association with human immunodeficiency virus among female sex workers
      in Lagos, Nigeria.
AB  - BACKGROUND AND OBJECTIVES: To determine the prevalence rates of serological
      reactivity of Haemophilus (H.) ducreyi, Treponema pallidum, and herpes simplex
      virus type 2 (HSV-2) antibodies among female sex workers (FSWs) and their
      association with human immunodeficiency virus (HIV) antibody status. STUDY
      DESIGN: Cross-sectional, standard serological assays were used for syphilis, HSV
      2 and HIV; a modified enzyme-linked immunosorbent assay (ELISA) was used to
      detect specific anti-H. ducreyi immunoglobulin (Ig) G and IgA antibodies.
      RESULTS: Seroprevalence rates were 86% for anti-H. ducreyi IgG and 69% for anti
      H. ducreyi IgA; 4% for rapid plasma reagin (RPR) and Treponema palladium
      hemagglutination assay (TPHA) confirmed syphilis; 59% for HSV-2; 12% for HIV-1
      and 2% for HIV-2. Lower-class FSWs were significantly more likely than upper
      class FSWs to be H. ducreyi seropositive (IgG: OR = 42.7; IgA: OR = 7.6) and have
      current or past syphilis infection (RPR: OR = 3.5; RPR and TPHA: OR = 4.5). The
      presence of syphilis increased significantly with older age (P-trend < 0.001).
      Non-Nigerian FSWs had significantly higher reactivity to chancroid (IgG: OR =
      3.5; IgA: OR = 1.8) and borderline reactivity to syphilis (RPR: OR = 1.6; TPHA:
      OR = 2.0). A history of sex with non-Nigerian Africans was significantly
      associated with chancroid reactivity and borderline significant with syphilis
      serostatus. H. ducreyi seropositivity was significantly more likely in FSWs with
      HSV-2 (OR = 2.4) and syphilis (OR = 5.6). Chancroid and HSV-2 antibodies were
      also more common in HIV-infected FSWs. CONCLUSION: The prevalence of H. ducreyi
      antibodies is the highest rate that has been reported. Our findings underscore
      the importance of an effective program to control GUDs as part of the strategy to
      prevent the potentially explosive spread of HIV in Nigeria.

PMID- 9587175
TI  - Detection of genital human papillomavirus and associated cytological
      abnormalities among college women.
AB  - BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) is strongly implicated in
      the etiology of cervical neoplasia; however, the frequency, rate, and predictors
      of neoplastic progression are unknown. GOAL: To measure the type-specific
      prevalence of cervical HPV and the rate of development of cytological
      abnormalities among a cohort of college women and to elucidate factors associated
      with acquisition of HPV DNA and progression to cytological abnormalities. STUDY
      DESIGN: Women 18 to 40 years of age seeking routine gynecologic care at a
      university health center were enrolled in a cross-sectional study with
      prospective, longitudinal follow-up of a subset of women. Demographic and
      behavioral data were collected using a written questionnaire. HPV DNA was
      detected in cervical scrapes by polymerase chain reaction using L1 consensus
      primers and a generic and 25 type-specific probes, and cervical cytological
      abnormalities were identified by Papanicolaou's (Pap) smear. RESULTS: HPV DNA was
      detected in 35% of the 414 women in the cross-sectional study; 66% of infections
      were with intermediate or high cancer risk HPV types. Multiple lifetime sex
      partners was an independent predictor of prevalent infection. Longitudinal
      analysis of 205 women showed that detection was transient (HPV DNA absent at
      follow-up) in 38% of the 84 women who were HPV-positive at enrollment. Persistent
      detection of the same HPV type at > or = 2 visits occurred in 14% of women and
      was significantly more common when intermediate or high cancer risk types were
      present. After 16 months of observation, 9% of HPV-infected women developed low
      grade squamous intraepithelial lesions (SIL) and 5% developed high-grade SIL; the
      risk of incident SIL was 7.8-fold higher among women who had persistent HPV
      detection with the same type. CONCLUSIONS: It was concluded that cervical HPV
      infection is highly prevalent among college women. Although most infections are
      caused by intermediate of high cancer risk types, few women (5%) developed high
      grade SIL during 16 months of observation.

PMID- 9587176
TI  - Chlamydia positivity versus prevalence. What's the difference?
AB  - BACKGROUND: Data on chlamydia screening collected as part of Regional Infertility
      Prevention Projects often do not include personal identifiers, therefore repeat
      tests for patients during a year cannot be identified. Consequently, positivity
      is calculated and used to monitor chlamydia prevalence. GOALS: To assess how well
      positivity can estimate prevalence in family planning and sexually transmitted
      disease (STD) clinic settings. STUDY DESIGN: Analyzed data from chlamydia
      screening programs in three geographic areas of the United States that used
      unique patient identifiers. RESULTS: The relationship between positivity and
      prevalence is related to both the percentage of tests that are repeat tests and
      the percentage of repeat tests that are positive. On average, the percentage of
      positive repeat tests was the same as or higher than prevalence in family
      planning clinics; thus, positivity was the same as or higher than prevalence. In
      STD clinics, the percentage of positive repeat tests was consistently lower than
      prevalence; thus, positivity underestimated prevalence. However, the absolute
      difference between positivity and prevalence was less than 0.5% in family
      planning and STD clinics. CONCLUSIONS: Positivity can be used to monitor
      chlamydia prevalence in women screened in family planning and STD clinic
      settings.

PMID- 9587177
TI  - Accuracy and costs of rapid human immunodeficiency virus testing technologies in
      rural hospitals in Zambia.
AB  - OBJECTIVE: To evaluate the accuracy and costs of newer rapid human
      immunodeficiency virus (HIV) antibody tests in primary health care settings in
      rural Zambia. METHODS: Three rural hospitals participated in this study. During a
      baseline assessment period, HIV testing practices were recorded on 250
      consecutive clients at each hospital. Baseline evaluation was compared with 250
      subsequent consecutive clients tested using a testing algorithm consisting of an
      initial screening HIV Dipstick test (McDonald Scientific [PVT] Limited, Harare,
      Zimbabwe) followed by confirmatory testing of all reactive specimens using the
      HIV Capillus test (Cambridge Diagnostics, Galway, Ireland), in conformity with
      World Health Organization HIV testing recommendations. Quality control was
      performed at a national university teaching hospital laboratory. RESULTS: A total
      of 1,500 clients was entered, with an HIV seropositivity rate of 53.2%. Most HIV
      testing was performed on patients with signs and symptoms suggestive of HIV
      infection. Same-day results were provided for only 16%. The HIV Dipstick testing
      algorithm sensitivity was 96.9%, and specificity was 98.0%. Counselor
      dissatisfaction was greater with the Dipstick algorithm as a result of 5.3%
      discordant results. Use of the HIV Dipstick testing algorithm cost between US
      $3.00 and US $3.80 per client tested. CONCLUSIONS: The accuracy of HIV testing in
      unsophisticated rural laboratories in Zambia is acceptable. Although HIV Dipstick
      testing algorithm costs were relatively high for a developing country, this HIV
      testing procedure is currently the most economical method available in Zambia.
      Accurate, less costly HIV testing algorithms are still needed.

PMID- 9587178
TI  - Long-term use of the female condom among couples at high risk of human
      immunodeficiency virus infection in Zambia.
AB  - BACKGROUND: Few studies have measured female condom use for more than a 6-month
      period or among persons at high risk of STD. OBJECTIVE: To measure long-term use
      of the female condom among couples at high risk of HIV infection and to evaluate
      the effect of female condom use on unprotected coital acts. STUDY DESIGN: Ninety
      nine Zambian couples with symptomatic sexually transmitted diseases (STD)
      received female condoms, male condoms, and spermicides and were counseled to use
      either condom plus spermicide for each coital act. Couples were followed up at 3
      , 6-, and 12-month visits. Barrier contraceptive use was measured prospectively
      by coital log. RESULTS: Among the 99 couples enrolled, 51, 38, and 30 couples
      were successfully followed up for 3, 6, and 12 months, respectively. Female
      condoms were reportedly used in 24%, 27%, and 23% of coital acts and by 86%, 79%,
      and 67% of the returning couples during each time interval. Higher-level female
      condom users used male condoms less often but had fewer unprotected coital acts
      (5% vs. 14%; p < 0.05) than lower-level female condom users. CONCLUSION: A
      majority of couples at high risk of HIV infection used the female condom in
      conjunction with other barrier methods over a 1-year period. The addition of
      female condoms accompanied by appropriate counseling to the barrier method mix
      may reduce unprotected sex among couples at high-risk of HIV infection.

PMID- 9587179
TI  - Use of DNA purification kits for polymerase chain reaction testing of Gen-Probe
      Chlamydia trachomatis PACE 2 specimens.
AB  - BACKGROUND AND OBJECTIVES: Confirmation testing using nucleic acid amplification
      has been shown to improve the sensitivity and specificity of screening tests for
      Chlamydia trachomatis. However, no critical information on the use of these
      techniques as an adjunct to Gen-Probe hybridization testing, one of the most
      common screening methods, has been reported to date. We examined the Roche
      AMPLICOR PCR C. trachomatis Test (Roche Diagnostic Systems, Branchburg, NJ) as a
      confirmatory test for the Gen-Probe PACE 2 C. trachomatis Test (San Diego, CA).
      Further, to mitigate the possible effect of interfering compounds in the Gen
      Probe PACE 2 transport medium, we tested various DNA purification techniques.
      STUDY DESIGN: C. trachomatis elementary bodies were used to spike PACE 2
      Transport medium, which was serially diluted, then tested by polymerase chain
      reaction (PCR). Six parallel dilution series were conducted: (1) saline dilutions
      tested by the Syva Direct Specimen Test, (2) Roche AMPLICOR transport medium
      dilutions tested by PCR, and (3-6) dilutions in PACE 2 transport medium purified
      respectively by GENECLEAN II (BIO101, Vista, CA), Puregene (Gentra Systems, Inc.,
      Research Triangle Park, NC), Microcon 100 (Amicon, Inc., Beverly, MA) DNA
      isolation kits, and no DNA purification, all tested by PCR. The system giving the
      best results by in vitro endpoint dilution trials was then used to confirm human
      specimens previously tested by the Gen-Probe method. RESULTS: PCR detected C.
      trachomatis at 11 twofold dilutions greater than PACE 2 and equivalent to
      detection of single elementary body by Syva Direct Specimen Test. DNA
      purification of spiked PACE 2 transport medium by the Microcon 100 kit produced
      the most consistent PCR detection endpoints, equivalent to endpoints of spiked
      AMPLICOR transport medium. Endpoints with no DNA purification step were variable
      and lower. Of 78 endocervical specimens negative by PACE 2 and Gen-Probe Probe
      Competition Assay, 12 (15.3%) were positive by Microcon DNA purification/PCR
      testing. CONCLUSIONS: PCR can be used as confirmation method for Gen-Probe PACE 2
      testing, but testing must be performed with a DNA purification procedure.

PMID- 9587180
TI  - Cycle helmets and the prevention of injuries. Recommendations for competitive
      sport.
AB  - The scientific evidence that bicycle helmets protect against head, brain and
      facial injuries has been well established by 5 well designed case-control
      studies. Additional evidence of helmet effectiveness has been provided from time
      series studies in Australia and the US. Bicycle helmets of all types that meet
      various national and international standards provide substantial protection for
      cyclists of all ages who are involved in a bicycle crash. This protection extends
      to crashes from a variety of causes (such as falls and collisions with fixed and
      moving objects) and includes crashes involving motor vehicles. Helmet use reduces
      the risk of head injury by 85%, brain injury by 88% and severe brain injury by at
      least 75%. Helmets should be worn by all riders whether the cyclist is a
      recreational rider or a serious competitor engaged in training or race
      competition. The International Cycling Federation (ICF) should make the use of
      helmets compulsory in all sanctioned races.

PMID- 9587181
TI  - Effects of thermal stress during rest and exercise in the paediatric population.
AB  - Thermoregulation during exposure to hot or cold environments differs between
      children and adults. Many physical and physiological changes occur during growth
      and maturation that can affect thermoregulation during rest as well as during
      exercise. Thus, physical as well as physiological differences between children
      and adults may explain the different response to thermal stress. The main
      physical difference between children and adults affecting thermoregulation is the
      much higher surface-area-to-mass ratio of children. In a warm environment this
      allows them to rely more on dry heat loss and less on evaporative cooling.
      However, in extreme conditions, hot or cold, the greater surface-area-to-mass
      ratio results in a higher rate of heat absorption or heat loss, respectively. The
      lower body fat in girls compared with women provides lower insulation and
      presents a disadvantage in a cold environment. The smaller blood volume in
      children compared with adults, even relative to body size, may limit the
      potential for heat transfer during heat exposure and may compromise exercise
      performance in the heat. The main physiological difference between children and
      adults is in the sweating mechanism, affecting their thermoregulation in the
      heat, but not in the cold. The lower sweating rate characteristic of children is
      due to a lower sweating rate per gland and not to a lower number of sweat glands.
      In fact, children are characterised by a higher density of heat-activated sweat
      glands. The lower sweating rate per gland may be explained by the smaller sweat
      gland size, a lower sensitivity of the sweating mechanism to thermal stimuli and,
      possibly, a lower sweat gland metabolic capacity. Other physiological differences
      between children and adults that may affect thermoregulation include metabolic,
      circulatory and hormonal disparities. The higher metabolic cost of locomotion in
      children provides an added strain on the thermoregulatory system during exercise
      in the heat. On the other hand, during acute exposure to cold it may prove
      advantageous by increasing heat production. Circulatory differences, such as a
      lower cardiac output at any given exercise intensity and the lower haemoglobin
      concentration in boys compared with men, are likely to increase the
      cardiovascular strain during exercise in the heat, although their effects in a
      cold environment are unknown. Finally, testosterone and prolactin are 2 hormones
      that differ in baseline levels between children and adults and may affect sweat
      gland function and sweat composition. These possible effects need to be further
      investigated. The effectiveness of thermoregulation is reflected by the stability
      of core temperature. In a thermoneutral environment, children are characterised
      by a similar rectal temperature and a higher skin temperature when compared with
      adults. The latter may reflect the higher reliance on dry heat loss compared with
      evaporative cooling in children. In a hot environment, children's body
      temperatures are higher compared with adults while walking and running but not
      necessarily while cycling. This may be related to the higher metabolic cost, and
      therefore higher heat production, in children while walking or running but not
      while cycling. In a cold environment, children are characterised by lower skin
      temperatures, reflecting greater vasoconstriction. Their metabolic heat is
      increased in the cold to a greater extent than that of adults, although this
      appears to be sufficient to maintain their body temperature during exercise but
      not during prolonged rest. Neither children nor adults sufficiently replace fluid
      loss during exercise in the heat. Nevertheless, recent studies suggest that in
      children, when the available beverage is flavoured and enriched with NaCl and
      carbohydrates, dehydration can be prevented. (ABSTRACT TRUNCATED)

PMID- 9587183
TI  - Age-related alterations in muscular endurance.
AB  - Aging often results in a decline of most physiological systems of the body.
      However, the maintenance of some appropriate level of neuromuscular function into
      old age is critical if we expect the elderly to be able to maintain normal daily
      activity and functional independence. It is well established that muscular
      strength declines in old age, but an equally important parameter of neuromuscular
      function muscular endurance, has received only minimal attention in the
      literature. Important information regarding age-associated changes in muscular
      endurance can be obtained from both animal and human research models, each having
      their own set of limitations and advantages. One problem in trying to interpret
      past research dealing in this area is the fact that muscular endurance can be
      expressed in a variety of ways and can be measured by a variety of techniques. It
      seems that conflicting reports arise from substantial differences in research
      design, statistical analyses or the ability to control extraneous influences such
      as physical activity levels and dietary intakes. This review will examine both
      human and animal literature in an attempt to elucidate methodological concerns in
      the assessment of muscular endurance and the controversial evidence regarding
      changes in muscle morphology and muscle metabolism that may be responsible for
      age-related changes in muscular endurance. Issues that address the possible
      selective loss of fibre type and the declines in both total fibre number as well
      as fibre size will be presented, since muscle quantity and quality have obvious
      links to endurance capacity. In conjunction with the alterations reported in
      skeletal muscle tissue, muscle blood flow and the relationship between fibre and
      capillary numbers and their possible influences on substrate availability will
      also be discussed in relation to muscle endurance capabilities. Finally, the
      adaptive ability of aged skeletal muscle to improve muscular endurance by
      different training regimens and through different physiological mechanisms will
      be investigated.

PMID- 9587185
TI  - An intracellular target for Helicobacter pylori vacuolating toxin.

PMID- 9587186
TI  - The persistence of (HIV in) memory (T cells).

PMID- 9587182
TI  - Strategies to enhance fat utilisation during exercise.
AB  - Compared with the limited capacity of the human body to store carbohydrate (CHO),
      endogenous fat depots are large and represent a vast source of fuel for exercise.
      However, fatty acid (FA) oxidation is limited, especially during intense
      exercise, and CHO remains the major fuel for oxidative metabolism. In the search
      for strategies to improve athletic performance, recent interest has focused on
      several nutritional procedures which may theoretically promote FA oxidation,
      attenuate the rate of muscle glycogen depletion and improve exercise capacity. In
      some individuals the ingestion of caffeine improves endurance capacity, but L
      carnitine supplementation has no effect on either rates of FA oxidation, muscle
      glycogen utilisation or performance. Likewise, the ingestion of small amounts of
      medium-chain triglyceride (MCT) has no major effect on either fat metabolism or
      exercise performance. On the other hand, in endurance-trained individuals,
      substrate utilisation during submaximal [60% of peak oxygen uptake (VO2peak)]
      exercise can be altered substantially by the ingestion of a high fat (60 to 70%
      of energy intake), low CHO (15 to 20% of energy intake) diet for 7 to 10 days.
      Adaptation to such a diet, however, does not appear to alter the rate of working
      muscle glycogen utilisation during prolonged, moderate intensity exercise, nor
      consistently improve performance. At present, there is insufficient scientific
      evidence to recommend that athletes either ingest fat, in the form of MCTs,
      during exercise, or "fat-adapt" in the weeks prior to a major endurance event to
      improve athletic performance.

PMID- 9587184
TI  - Iliopsoas bursitis and tendinitis. A review.
AB  - This review examines the diagnosis and management of iliopsoas bursitis and/or
      tendinitis. It is a relatively uncommon and unrecognised cause of anterior hip
      pain and anterior snapping hip. In view of its pathology, iliopsoas bursitis
      might be better referred to as iliopsoas syndrome. It can usually be diagnosed by
      history and physical examination, though real time ultrasound may be useful in
      confirming the diagnosis. Magnetic resonance and computerised tomography imaging
      have limited roles in its diagnosis, but may identify other pathology or surgical
      lesions. Nonoperative management has not been well established. Surgical
      management does not guarantee treatment success. There is a need for further
      research into both diagnostic and treatment options for those patients with
      iliopsoas bursitis/tendinitis.

PMID- 9587187
TI  - Typhoid fever--important issues still remain.

PMID- 9587188
TI  - The significance of superantigens.

PMID- 9587189
TI  - Intracellular pathogens: the role of antibody-mediated protection in Salmonella
      infection.

PMID- 9587190
TI  - Life in grasses: diazotrophic endophytes.
AB  - N2-fixing bacteria such as Azoarcus spp., Herbaspirillum spp, and Acetobacter
      diazotrophicus can infect the interior of gramineous plants without causing
      symptoms of plant disease but do not survive in soil. Like phytopathogens, they
      can penetrate into central tissues and spread systemically. There is no evidence
      for an endosymbiosis in living plant cells; however, the bacteria are
      physiologically active in the plant apoplast.

PMID- 9587191
TI  - Telomeres and HIV-1 infection: in search of exhaustion.
AB  - Telomere length analysis could be helpful in determining if exhaustion and
      replicative senescence are involved in HIV-1 pathogenesis. Evidence that CD8+ T
      cells have shorter telomeres may point towards an increased turnover of CD8+ T
      cells and exhaustion of the CD8+ T-cell responses in HIV-1 infection. In CD4+ T
      cells, the relationship between telomere length and turnover remains
      controversial; however, telomere length analysis argues against exhaustion of
      CD4+ T cells.

PMID- 9587192
TI  - Human leukocyte antigens in tuberculosis and leprosy.
AB  - Human mycobacterial infections are characterized by a spectrum of clinical and
      immunological manifestations. Specific human leukocyte antigen (HLA) factors are
      associated with the subtypes of leprosy that develop and the course of
      tuberculosis after infection. The identification of protective mycobacterial
      antigens presented by a broad variety of HLA molecules will have important
      implications for the design of vaccines.

PMID- 9587194
TI  - Molecular identification of novel viruses.
AB  - Viruses are responsible for many of the diseases caused by microbial infection.
      During the past two decades, approximately 20 new human viruses have been
      discovered. Many of these new viruses were initially identified using molecular
      biology techniques, a major advantage of which is the ability to search rapidly
      for new viruses, known viruses or related, but previously unidentified, members
      of established virus families in disease samples.

PMID- 9587193
TI  - Antibacterial and anti-inflammatory agents that target endotoxin.
AB  - Antibiotic-resistant bacterial infections are a major clinical problem. Lipid A,
      the active part of lipopolysaccharide endotoxins in Gram-negative bacteria, is an
      intriguing target for new antibacterial and anti-inflammatory agents. Inhibition
      of lipid A biosynthesis kills most Gram-negative bacteria, increases bacterial
      permeability to antibiotics and decreases endotoxin production.

PMID- 9587195
TI  - DNA marker C04107 for copper toxicosis in a population of Bedlington terriers in
      the United Kingdom.
AB  - The DNA microsatellite marker C04107, linked to the Bedlington terrier copper
      toxicosis locus, is used diagnostically in the USA to detect the disease allele.
      This marker has been typed in Bedlington terriers of known disease status in the
      United Kingdom, and it is concluded that it should be useful in eradicating the
      disease from the breed in the UK. The marker also identified a dog which had been
      diagnosed on the basis of a liver biopsy as having the disease, as being
      unaffected; a second liver biopsy confirmed that the dog did not have copper
      toxicosis.

PMID- 9587197
TI  - Evaluation of flea control strategies using fipronil on cats in a controlled
      simulated home environment.
AB  - Three groups of six cats were kept in similar carpeted pens in which a self
      replicating population of Ctenocephalides felis had been established. One group
      was left untreated, but the other groups were treated every 28th day with 0.5 ml
      of a 10 per cent fipronil spot-on formulation, and the cats in one of the treated
      groups also wore a methoprene collar. No fleas were found on any of the treated
      cats, either during the first 13 weeks of the study, when heavy flea burdens were
      developing in the control pen, or over the next 11 weeks when a declining number
      of fleas was present on the control group.

PMID- 9587196
TI  - Detection of feline parvovirus in dying pedigree kittens.
AB  - Feline parvovirus (FPV) was detected in the intestinal tract contents of 13
      pedigree kittens which were fading or died suddenly by the use of a new
      chromatographic test strip for canine parvovirus (CPV) and FPV. The test appeared
      to be sensitive and specific for the detection of FPV and was a useful diagnostic
      aid. In three cases in which virus was grown in cell culture, the isolates were
      characteristic of FPV and not CPV. Cats in the households in which the kittens
      were reared were regularly immunised with FPV vaccines. The most likely
      explanation for the occurrence of FPV-associated disease was exposure of the
      young kittens to large doses of virus contaminating the environment.

PMID- 9587199
TI  - Diagnosis of cranial cruciate ligament injury in dogs by tibial compression
      radiography.
AB  - Stress radiographs were taken of 42 sound stifle joints, of five stifles with
      injuries other than cruciate disease, and of 72 stifles with surgically confirmed
      cranial cruciate damage. The stifles were also examined by the cranial drawer
      test. No false positive compression radiographs were obtained. In the 72 stifles
      with cranial cruciate damage, instability was diagnosed on the stressed view in
      all but two cases. The sensitivity of the radiographic tibial compression test
      was 97 per cent, compared with 86 per cent for the cranial drawer test; the
      specificities of the tests were 100 per cent and nearly 98 per cent,
      respectively.

PMID- 9587198
TI  - Surgical treatment of intrahepatic portosystemic shunts in 45 dogs.
AB  - The surgical attenuation of an intrahepatic portosystemic shunt in 45 dogs is
      described. Twenty-nine (64 per cent) had left divisional shunts consistent with a
      patent ductus venosus (PDV), 15 (33 per cent) had central divisional shunts and
      one had a right divisional shunt. In the dogs with a PDV, the shunt vessel could
      be most easily manipulated at a posthepatic site, whereas in those with central
      and right divisional shunts the manipulation could be more easily made
      intrahepatically but sometimes involved demanding intravascular surgical
      techniques. Eight dogs (18 per cent) died during the surgery or shortly
      afterwards. Of the 37 dogs surviving longer term, 28 (76 per cent) became
      clinically normal and required no medication or diet control. In a further three
      animals the shunt was ligated completely only during a second surgical procedure.
      The remaining six dogs were euthanased because of clinical signs of
      encephalopathy which were either surgically or medically uncontrollable.

PMID- 9587200
TI  - Complications of treating presumed pseudopregnancy in pregnant bitches.

PMID- 9587201
TI  - Rectal perforation associated with pelvic fracture in a cat.

PMID- 9587202
TI  - Cat castrations and veterinary nurses.

PMID- 9587203
TI  - Fluoroquinolone susceptibility of S typhimurium DT104.

PMID- 9587204
TI  - Tail-biting and tail-docking in pigs.

PMID- 9587205
TI  - Booster intervals for vaccines.

PMID- 9587206
TI  - Dermal fibropapillomas in cats.

PMID- 9587207
TI  - Unusual ocular condition in Burmese cats.

PMID- 9587208
TI  - Electrocution of horses and cattle.

PMID- 9587209
TI  - A new electrocardiographic approach to identify the coronary artery responsible
      for acute inferior myocardial infarction: a study in 100 patients.
AB  - OBJECTIVE: The objective of this study is to analyze the value of the
      electrocardiogram in the identification of the coronary artery responsible for
      acute inferior myocardial infarction. MATERIAL AND METHODS: One hundred
      consecutive patients with acute inferior myocardial infarction were studied, 67
      with a lesion in the right coronary artery and 33 in the circumflex artery. The
      ST segment changes in the inferior, lateral, precordial and right-chest leads
      were analyzed, as well as the arithmetic sum of the ST segment in the inferior
      and V2 leads (II + V2, III + V-2 and aVF + V2). We also developed a diagnostic
      process based on a stepwise approach of three electrocardiographic criteria: a)
      elevation of the ST segment in DI; b) arithmetic sum of the ST magnitude in DIII
      + V2 < 0; c) depression of the ST segment in V4R. RESULTS: This study shows that
      the most useful parameters to predict (with a specificity of 100%) the lesioned
      coronary artery in acute inferior myocardial infarction are: a) the arithmetic
      sum of the ST segment: aVF + V2 > 0, for the right coronary artery; b) the
      arithmetic sum of the ST segment: III + V2 < 0, for the circumflex artery; c) the
      arithmetic sum of the ST segment: aVF + V2 > 1 mm, for the proximal right
      coronary artery. CONCLUSIONS: The incorporation of these three criteria in an
      algorithm diagnostic system allows us to locate the coronary artery responsible
      for acute myocardial infarction with 100% sensitivity and specificity.

PMID- 9587210
TI  - Cardiac consequences of renal transplantation changes in left ventricular
      morphology.
AB  - OBJECTIVE: The aim of this study was to characterize changes in left ventricular
      morphology and function by conventional echocardiography in a pediatric
      population after renal transplantation (RT). MATERIAL AND METHODS: This study
      includes 21 children, 11 female and 10 male, aged 11.8 +/-2.6 years at the time
      of renal transplantation. Eleven were on regular hemodialysis treatment and two
      on continuous peritoneal dialysis for 31.8 +/- 31.6 months; eight were
      transplanted without prior dialysis. Eight children were hypertensive before RT
      and nine (seven de novo) after RT. The patients were analysed in a prospective
      follow-up study with echocardiography immediately before and 30.2 +/- 15 months
      after successful renal transplantation. We measured the following
      echocardiographic parameters: Left ventricular end diastolic (LVED) and end
      systolic diameter (LVES), left atrial dimension (LAD), septal thickness (IVST),
      posterior wall thickness (PWT), shortening fraction (SF) and left ventricular
      index mass (LVIM). The paired Student's test, Fisher exact test and Pearson's
      correlation were used for statistical analysis. We analyzed the echocardiographic
      changes in the total group and separately in the subgroups with and without prior
      hemodialysis, as well as the influence of the duration of dialysis, anemia and
      hypertension. RESULTS: 1. After renal transplantation we found a decrease in the
      LVED LVES, LAD, IVST and PWT measurements (p < 0.05). There was a negligible
      increase in SF. The LVIM decreased from 139 g/m2 to 104 g/m2, representing a 21%
      reduction of the initial value, but this reduction was not of statistically
      significant. 2. The findings were similar in the hemodialysis group-LVIM
      decreased from 167.6 g/m2 to 94.9 g/m2, representing a 35% reduction in the
      initial value. 3. In the non dialysis group LVED, LVES, LAD and SVT decreased and
      LVIM showed a minor increase. There was a negligible increase in SF. 4. We found
      an increased LVIM in children with prior hemodialysis before RT, especially if
      dialysis lasted for more than two years. 5. Amelioration of hematocrit correlated
      with reduction of LVIM. 6. Regression of LV hypertrophy after RT was not
      dependent on blood pressure levels. CONCLUSIONS: Renal transplantation resulted
      in a tendency towards normalization of the echocardiographic parameters analysed:
      Contractility, as assessed by shortening fraction, was normal in this population.
      Although cardiac hypertrophy and dilation is reversible after RT, it would seem
      that children may benefit from an earlier transplantation.

PMID- 9587211
TI  - [Primary hyperaldosteronism: report of 2 clinical cases].
AB  - The authors report two cases of primary hyperaldosteronism (Conn's adenoma and
      hyperplasia). Based on available data, the authors discuss clinical laboratory
      and imagiologic evaluation, the factors influencing prognosis, strategy and the
      results of the proposed therapies.

PMID- 9587212
TI  - [Coronary bypass surgery and cardioverter-defibrillator implanted in patients
      with malignant ventricular arrhythmia and ischemic cardiopathy].

PMID- 9587213
TI  - [Late potentials and ventricular arrhythmia after surgical repair of Tetralogy of
      Fallot].

PMID- 9587214
TI  - [Effects of nitric oxide on heart function].

PMID- 9587215
TI  - [Systolic relaxation-pressure relationship. A load independent approach to
      evaluate cardiac function].

PMID- 9587216
TI  - [Significance of calcium kinetics in the modulation of relaxation by load].

PMID- 9587217
TI  - [Aneurysms of the interauricular septum diagnosed with transesophageal
      echocardiography: relationship with cerebrovascular events].

PMID- 9587218
TI  - [Longitudinal study of arterial pressure in youngsters and young adults].

PMID- 9587219
TI  - [Functional capacity after heart transplantation].

PMID- 9587220
TI  - [Measurement discrepancies (analysis of consistency between 2 methods)].
AB  - Our purpose was to study the agreement between two methods with clinical impact.
      Usually, many techniques are not correct for the analysis of concordance.
      Otherwise, it is normal to confuse association and concordance. We intend to
      prove that two methods can show a strong association and a weak concordance.
      Nowadays we must replace "old" methods with new ones, which are more correct and
      efficient for clinical and research goals.

PMID- 9587221
TI  - [What modifies the stability of an artificial joint?].

PMID- 9587222
TI  - [Familial giant hemangiomas of the liver. Study of a family and review of the
      literature].
AB  - In this report we present for the first time strong evidence for autosomal
      dominant inheritance of grant liver hemangiomas. Furthermore, we review the
      current literature about incidence, pathogenesis, clinics, as well as diagnostic
      and therapeutic aspects of LH. A large family of Italian origin is described
      where three female patients in three successive generations suffered from large
      symptomatic LH. In addition, two other female relatives exhibited asymptomatic LH
      on sonographic scans. The restriction of the disease to the female gender could
      be explained by a sex-dependent difference in penetrance or expressivity of a
      presumable "liver-hemangioma" gene, or by known proliferative factors such as
      female sex hormones. We also observed an increased incidence of adenomas of the
      thyroidea among members with or without LH of the presented family. This uncommon
      familial association has also not yet been described and its genetic aspects are
      discussed.

PMID- 9587223
TI  - [Tuberculosis in the Swiss Army during World War II, results of army mass chest x
      ray 1943/44--a valuable historical reminiscence].
AB  - Army mass X-ray fluoroscopic screening (ARD) included the group of service
      personnel performing its military service in the Swiss army in the years 1943/44.
      ARD was at that time regarded as a measure targeted against tuberculosis, and was
      ordered by the Chief of the General Staff, at the request of the Head of the Army
      Medical Service. A total of 516,879 conscripts were examined. Of these-
      corresponding to the structure of the army--the infantry with 265,640 conscripts
      made up 51.4% of those examined in this way. As a result a total of 967 cases of
      active pulmonary tuberculosis were discovered and recorded in the army. This
      total was made up of 395 so-called active-open and 572 active-closed cases.
      Inactive pulmonary tuberculosis of the lungs occurred in 1,642 conscripts. The
      total number of 967 carriers of an active pulmonary tuberculosis corresponded-
      when converted--to an incidence of 187/100,000 persons. The 6,186 cases of
      hardened primary complexes, further multiple hardenings in the lung and pleuritic
      adhesions, probably mostly of tuberculous origin at that time, recorded in
      addition during the mass screening may also be regarded as evidence of a
      considerable "epidemic resistance" among military personnel. In comparison to
      foreign European armies--though with smaller numbers examined--the Swiss figures
      are lower.

PMID- 9587224
TI  - [General practice of lumbosacral peridural infiltrations in rheumatology:
      considerations based on a review of the literature].
AB  - Recommendations about the practice of epidural steroid injections for low back
      pain and sciatica are formulated based on an extensive review of the published
      literature. These infiltrations should be reserved to trained physicians
      observing strictly aseptic conditions. Their indications are limited to the few
      special situations where classical treatments have failed, and only after
      exclusion of an infectious or tumoral process. To the present time no conclusive
      data have been published to prove that these procedures reduced the need for
      surgery in the case of herniated nucleus pulposus or spinal stenosis. Their
      efficacy on the intensity of pain is also controversial. Some improvement on pain
      and functional scores may be observed for a few weeks but this positive effect
      disappears 2 or 3 months post-injection.

PMID- 9587225
TI  - [Livedo reticularis, acral necroses and renal failure. Cholesterol crystal
      embolisms].
AB  - In a 67 year old patient with multiple cardiovascular risk factors a livedo
      reticularis, ischemic acral lesions as well as deterioration of renal function
      five weeks after cardiac catheterism and aorto-coronary bypass surgery led to
      suspicion of cholesterol embolism. Fundoscopy revealed cholesterol crystals in
      retinal vascular branches thus delivering important diagnostic information.
      Atheromatous lesions of the entire aorta and the ilio-femoral arteries were
      possible sources for embolism. The outcome was favorable. The lesions of the toes
      regressed and renal failure did not progress to dialysis. The diagnostic steps
      taken, the clinical picture of cholesterol embolism, the use of imaging and
      therapeutic options are discussed.

PMID- 9587226
TI  - [Hepatopathy in HIV and AIDS].

PMID- 9587227
TI  - [Comment on G. Schubiger, D. Desgrandchamps: Routine vaccinations].

PMID- 9587228
TI  - [Accident medical expert assessment in Switzerland--does it meet current quality
      requirements?].
AB  - QUESTION: Is the quality of the expert reports and the advises of physicians who
      evaluate injuries good enough to satisfy legal standards in Switzerland? METHODS:
      262 expert reports were analysed for precise wording, documentation, and for
      their impact on conclusive judgement. Each report was evaluated for accurate
      patient history, which also included the patients subjective complaints,
      objective findings, diagnosis, and final evaluation by the physician. RESULTS:
      Only a third of the expert reports satisfied all the aspects requested for
      accurate handling of the case. In two third of all cases, one or more important
      parts were missing. This lack of complete evaluation precluded a correct
      judgement and questions the adequate settlement of those cases. CONCLUSIONS: The
      standards for medical expert reports and legal advises have to be redefined. We
      propose to increase the quality of expert reports by further educating physicians
      who are involved in trauma care.

PMID- 9587229
TI  - [Blunt thoracic trauma with hemorrhage into a mediastinal lymphangioma--case
      report].
AB  - We describe a young snowboarder suffering from dyspnea, chest pain and dysphagia
      following a blunt chest injury. These symptoms were caused by an accident-related
      hemorrhage within a preexisting lymphangioma of the right posterior mediastinum.
      At the same time a lymphangioma of the left anterior mediastinum was found. The
      lymphangioma of the posterior mediastinum was resected through a right
      posterolateral thoracotomy after thoracoscopy had demonstrated that a complete
      resection could not be performed on this way. The lymphangioma of the left side
      was resected 4 month later by a left-sided hemiclamshell approach due to its size
      and localisation. Complications arising from mediastinal lymphangioma are
      described as compression, infection, spontaneous bleeding, rupture and
      chylothorax. This is the first description of a posttraumatic, symptomatic
      hemorrhage within a mediastinal lymphangioma.

PMID- 9587230
TI  - Direct repair of right atrial rupture after blunt chest trauma without
      cardiopulmonary bypass.
AB  - Tamponade from free wall rupture of the cardiac chambers following blunt thoracic
      trauma is relatively frequent. Diagnosis requires a high index of suspicion and
      is rapidly confirmed by echocardiography. Emergent surgery is always mandatory
      despite apparent stable vital signs. We report a successful repair of a lacerated
      right atrium without cardiopulmonary bypass (CPB), saved in extremis after undue
      in-hospital delay.

PMID- 9587231
TI  - [Biomechanics of the ankle joint--injury mechanisms].
AB  - The complex mechanics of the ankle joint complex depends highly on the integrity
      of the ankle ligaments. An incomplete restoration of the antero-fibular ligament
      after trauma may result in a mechanical dissociation of the talus from the ankle
      mortise. The force that is needed to induce a non-physiological movement of the
      foot is determined by the individual configuration of the bony and articular
      structures of the hindfoot. A pes cavus is less protected to suffer of an ankle
      sprain than a flatfoot. As the leverarm of the peroneal muscles decreases with
      increasing plantarflexion of the foot, the active protection to resist against a
      supination stress decreases with plantarflexion. These findings have significant
      implications for the practice. First of all an adequate treatment of any ankle
      sprain is necessary to restore the mechanical interplay of the ankle joint
      complex. Ankle orthoses should protect the foot against supination stress and
      excessive plantarflexion. The prevention of ankle injury may be significantly
      improved by recognition of the individual mechanical disposition.

PMID- 9587232
TI  - [Ankle joint injuries in children. Chief presentation of the 83rd Annual Meeting
      of the Swiss Society of Traumatology and Insurance Medicine, 4-5 September 1997,
      Winterthur].
AB  - Children are not just small adults. Depending on age and skeletal maturity, they
      demonstrate typical lesions. All major ankle ligaments, except the interosseous
      ligament, either insert or originate from the tibial and fibular epiphysis. In
      young children, the physeal structures are more likely to break than the
      ligaments. After a sprain of the ankle, we observe avulsion fractures of the
      ligaments or physeal fractures as described by Salter and Harris. In adolescents
      ligamentous ruptures can occur and, because of the asymmetric physeal closure,
      two- and threeplane fractures (transitional fractures) appear.

PMID- 9587233
TI  - [Acute ruptures of the Achilles tendon--apropos of 14 conservatively treated
      cases].
AB  - GOAL OF THE STUDY: To analyse the results of non surgical treatment (cast for 12
      weeks) for complete and recent rupture of Achilles tendon. MATERIAL AND METHODS:
      We reviewed with an average follow up of 2 years 14 patients (14 ruptures). All
      patients evaluated subjective results on a linear scale. Objective results were
      given by clinical examination, ultrasonography and performance testing. RESULTS:
      Subjective results were excellent for 50% of cases, good for 29% and fair for
      21%. Amyotrophy of the calf was always noted (mean 15 cm). The maximum force was
      reduced by 22% and the endurance by 47% in comparison with the healthy calf. All
      sportsmen but one were able to continue their sport as before. None of them had
      to change their job. DISCUSSION: The conservative treatment of fresh ruptured
      Achilles tendon by plaster cast for 12 weeks gives satisfactory results in
      comparison with surgical treatment followed by 6 weeks immobilisation. The
      results are not so good when compared to conservative or surgical treatment
      followed by immediate mobilisation. CONCLUSION: Conservative treatment by plaster
      cast for 12 weeks should be applied to non compliant patients or to patients who
      are not concerned by the functional results or unable to follow a programme of
      reeducation or to patients with chronic skin lesions.

PMID- 9587234
TI  - [Subtalar arthrodesis--minimal resection technique].
AB  - INTRODUCTION: This is a prospective clinical and radiological study of the
      treatment of talocalcaneal deformity or degeneration by a modified technique of
      isolated talocalcaneal fusion. METHODS: Thirty-six patients were evaluated with
      clinical examination, plain dorso-plantar and oblique x-rays and CT-scan or
      magnetic resonance imaging in a follow-up of 32.5 months (range: 20-62). In 12
      cases a posterior tibial tendon rupture with secondary osteoarthritis and in 24
      cases a posttraumatic secondary osteoarthritis (18 calcaneal fractures, 3 talar
      fractures, 2 axial traumas with secondary talar necrosis and 1 rheumatoid
      arthritis with calcanear and talar fracture) were the indications for arthodesis.
      RESULTS: On a visual analog pain scale the patients graded their pain
      preoperatively at 4.4 and postoperatively at 1.1. The subjective results showed
      in 12 cases (33.3%) complete satisfaction, in 10 cases (27.7%) satisfaction with
      minor reservation, in 11 cases (30.5%) satisfaction with major reservation and in
      3 cases (8.5%) dissatisfaction. The overall objective results were excellent in
      17 (47.2%), good in 11 (30.5%), fair in 6 (16.8%) and poor in 2 (5.5%) cases. A
      further advantage of this type of talocalcaneal fusion is the remaining range of
      motion in the neighbouring joints, at the ankle (in 75.7% the same or better ROM
      than preoperatively) and at Chopart joint (in 69.4% the same or better ROM than
      preoperatively). The fusion rate was high with 94.5%. CONCLUSION: The modified
      isolated talocalcaneal fusion without disruption at the Chopart joint is a simple
      surgical technique in the hand of the experienced surgeon. The subjective and
      objective mid-term results of this prospective follow-up study are comparable to
      other technique described in literature.

PMID- 9587235
TI  - LC-DC plating with bone graft in posttraumatic nonunions in the middle third of
      the clavicle.
AB  - Nonunions and malunions of the clavicle are uncommon but can be disabling,
      causing pain, limitation of shoulder motion or local brachial plexus compression.
      Reconstructive procedures are focused on gaining union and restoring functional
      clavicular anatomy. We would like to present a surgical procedure in which an
      autologous iliac crest graft and a 3.5 mm low contact-dynamic compression plate
      (LC-DCP) are used to regain clavicular stability and union. Surgery was performed
      in all eight patients for symptomatic nonunion. Eight patients treated by this
      method between 1991-1996 showed clinical and radiological union after an average
      follow-up time of eight months. All patients were highly satisfied with the
      surgical result. The advantages of the LC-DCP in the internal fixation of
      clavicular nonunions with its demanding anatomical and biomechanical
      characteristics are presented.

PMID- 9587236
TI  - [Surgical treatment of proximal humerus fractures--international multicenter
      study].
AB  - To receive an overview of the presently used methods for the operative treatment
      of fractures of the proximal humerus a prospective controlled multicenter study
      was arranged. 146 fractures from 145 patients (76 females, 69 men) were assessed,
      documented with the AO standard sheets and radiographs and with a one year follow
      up examination. Each of the nine clinics used his own treatment scheme. They
      applied: K-wires (27%) for adaptation and for intramedullary fixation; tension
      band wires (16%) or sutures (11%) alone or in combination with K-wires;
      osteosynthesis with screws alone (7%) or with plates (22%). In 17% the humeral
      head was acutely replaced with a prosthesis. 11 fractures (8%) had to be
      reoperated because of instability or loss of fixation. 109 patients were
      available for clinical review, one patient could be questioned by letter and six
      patients had died after one year (follow-up 80%). In 38% of patients full limb
      function was restored, slight impairment persisted in 45% and 17% remained
      severely handicapped. 96 fractures (89%) were consolidated, 30% with a deformity.
      35% of patients still were unable to work full time. The treatment of fractures
      of the proximal humerus is generally difficult. More over the various operative
      methods and problematic fracture classification make a differentiate statistical
      analysis impossible. Still many questions remain. For answers a new trial is
      mandatory. For this future series fixed guidelines for indications and operative
      treatment modalities are required to allow a meaningful comparison of results and
      a scoring system for evaluation of functional outcome is necessary.

PMID- 9587237
TI  - [Professional information].

PMID- 9587238
TI  - [Psychological stress and workload changes in the professional world].

PMID- 9587239
TI  - [Prognosis of bronchial asthma].
AB  - Little is known about the prognosis of asthma. Disease remission in adolescence
      has been reported to vary between 20-80%, but bronchial hyperresponsiveness can
      still be detected in most subjects even if they are without symptoms. The relapse
      rate of asthmatics who were without symptoms during adolescence amounts to about
      30%. Severe disease at an early stage or in adolescence, atopy, atopic
      dermatitis, a high degree of bronchial hyperresponsiveness, severely impaired
      lung function and both active and passive smoking are risk factors and closely
      associated with a poor prognosis. The relevance of gender, age at onset or
      recurrent viral infections has not been clarified yet. The effect of
      environmental factors on the increasing incidence and the prognosis of asthma
      remains to be quantified.

PMID- 9587240
TI  - [Regeneration of the heart muscle after myocardial infarct].
AB  - Myocardial infarction is characterized by the loss of contractile cardiomyocytes.
      This results in an increased load on the spared myocardium. The aim of this
      article is to describe the response of the non-affected myocardium after
      infarction. Human hearts were investigated by microscopical, biochemical and
      cytophotometrical methods. The number of nuclei was calculated from the numerical
      ratio of connective tissue nuclei/myocyte nuclei, the values of the total DNA
      amount and the percentage proportion of the various ploidy classes in the myocyte
      nuclei. After myocardial infarction the DNA concentration as well as the DNA
      content was increased. Different DNA distribution pattern could be found in
      infarcted hearts. Percentage proportion of higher ploid nuclei and aneuploid
      nuclei was increased. Number of connective tissue nuclei was increased in
      infarcted hearts. And, in spite fibrosis of the necrotic area, number of myocyte
      nuclei did not change significantly. Beside scarring of the necrotic tissue,
      hypertrophy and hyperplasia of cardiomyocytes occur after myocardial infarction
      and may compensate the loss of contractile fibres to guarantee myocardial
      function.

PMID- 9587241
TI  - [Driving fitness in therapy with antidepressive drugs].
AB  - The driving ability of patients under therapy with antidepressives is seen less
      restrictive than some years ago. The inhibition of psychomotor performance is of
      special interest. Some empirical studies point at antidepressives increasing the
      risk for accidents at least in elderly patients. Different groups of
      antidepressants apparently show different effects. Tricyclic antidepressants were
      shown to worsen cognitive and psychomotor performance in some patients while
      serotonin reuptake inhibitors and some other new antidepressants may cause less
      behavioral toxicity. Methodological problems in assessing driving ability and
      some recent findings are discussed.

PMID- 9587242
TI  - [Length of stay of patients with alcohol abuse or alcohol dependence in internal
      medicine and surgery].
AB  - To determine the length of stay (LOS) of alcoholic and non-alcoholic patients,
      all consecutive admissions to medical and surgical departments of a general
      hospital in Lubeck, Germany, were registered over a period of six months. The
      study sample comprised 625 medical and 661 surgical patients aged 18 to 64 years,
      42% female. Alcohol abuse and dependence were detected using an expert interview
      (Schedules for Clinical Assessment in Neuropsychiatry, SCAN). The median LOS of
      patients with alcohol abuse or dependence was equal to that of the other patients
      (Z = 9 days). Differences occurred in the surgical clinic where alcohol abusers
      as well as alcohol dependent patients stayed longer than the others. There was
      significant trend in the medical clinic towards longer LOS for alcohol abusers
      and shorter LOS for alcohol dependent patients compared to the other medical
      patients respectively. Patients suffering from infections, tumors or
      gastrointestinal diseases had significantly increased LOS if having an alcohol
      problem. In conclusion, there is no general elongation of LOS in alcoholic
      patients. Differences occur if single departments or somatic or psychiatric
      subgroups of patients are regarded. However, high concentrations of alcohol
      related diseases in these settings stress the importance of preventative
      measures.

PMID- 9587243
TI  - [Occupational spinal diseases in employees of nursing services--epidemiological
      and legal insurance aspects (III). 3: Intervertebral disk-induced diseases of the
      lumbar spine in health care employees--expert assessment and prevention].
AB  - Due to spine-loading activities nursing professionals have a relatively high
      incidence/prevalence of low back pain. As lumbar disc disorders can be regarded
      as occupational diseases (since January 1993, occupational disease BK 2108,
      normally more than 10 years of exposition, lumbar disc disorders with pain and
      reduced motility) international literature is reviewed. Own results of different
      prevalence-, case-control- and incidence studies (relative risk for lumbago
      sciatica/odds ratio for disc prolaps appr. 3-6 depending on age and occupational
      age) are presented. Finally the question of compensation and prevention of disc
      disorders is discussed.

PMID- 9587244
TI  - [Comment on H.-D. Hentschel: On the development of the "natural healing" concept
      and R. Hakimi: Natural healing versus alternative medicine--attempt at a
      differentiation].

PMID- 9587245
TI  - Assessment of exposure to indoor air pollutants.

PMID- 9587246
TI  - Assessing the health consequences of major chemical incidents--epidemiological
      approaches.

PMID- 9587247
TI  - Recent advances in biomaterials.
AB  - Biomaterials for medical use have been developed in accordance with progress of
      the fields of medicine, biochemistry, material science, and pharmaceutics.
      Advances in the medicine have changed the concept of surgery from the deletion of
      damage tissue for the preservation of the remaining healthy tissue to the
      reconstruction or replacement of damaged tissue by promoting regeneration of the
      natural tissue. All the materials used in medicine should be biocompatible.
      Conventional materials such as metals, ceramics, and synthetic polymers are
      usually bioinert and support the structural defects. But recently introduced
      biomaterials are designed to provide biological functions as much a possible by
      mimicking natural tissue structures.

PMID- 9587248
TI  - The role of acromioclavicular arthritis in impingement syndromes.
AB  - The role of acromioclavicular (A-C) arthritis in stage 2 and 3 impingement
      syndromes was investigated in this study. Twenty-seven patients with stage 2 and
      3 impingement syndrome were evaluated both clinically and radiologically for the
      presence of A-C arthritis. Patients with A-C arthritis who were treated by
      conservative or surgical methods were rated before and after therapy according to
      the University of California at Los Angeles (UCLA) shoulder rating scale. The
      follow-up period ranged from 7 to 16 months, with an average of 13 months. A-C
      arthritis was diagnosed in 21 of 27 patients (one grade 2 and 20 grade 3,
      according to Kellegren). Clinical and radiological evaluation of these 21
      patients revealed A-C joint pain and a positive lidocaine injection test in all
      (100%), a positive horizontal adduction test in 20 (95.2%), decreased joint space
      in 18 (85.75%) and osteophytes in 11 (52.4%). Surgical treatment was considered
      for 12 A-C arthritis patients; and distal clavicle resection was performed in 11
      of these cases. The average score measured by the UCLA rating scale increased
      from 13 to 28 in the group treated with surgery (satisfactory result), and from
      10 to 13 in the group treated with conservative therapy (unsatisfactory result).
      The results of this study may be interpreted as demonstrating that A-C arthritis
      is a common etiologic factor in chronic impingement syndromes and its co
      existence has a strategic importance in the choice of treatment method. Surgical
      resection of the distal clavicle should be considered in the presence of this
      pathology since this technique provides excellent results in pain relief and
      appears to be superior to conservative therapy in these cases.

PMID- 9587249
TI  - Correlation of brain CT findings and developmental outcome in patients with
      spastic cerebral palsy.
AB  - Brain computed tomography (CT) is a useful tool for evaluating the pathologic
      findings in the brains of children with neurologic abnormalities. Brain CT
      investigation and the Munchner Funtionelle Entwicklungs Diagnostik (MFED)
      developmental assessment was performed in 88 patients with spastic cerebral
      palsy. The incidence of abnormal brain CT findings in patients with spastic
      cerebral palsy was 69.3%. The group with pathologic CT findings had a greater
      possibility of having developmental delay than the group with normal CT findings
      (p < 0.05). However, there was no significant relationship between the specific
      MFED categories and the types of brain CT abnormalities. Pathological CT findings
      could offer important prognostic information indicating a higher risk concerning
      the grade of developmental delay.

PMID- 9587250
TI  - Identification of Tyrophagus putrescentiae allergens and evaluation of cross
      reactivity with Dermatophagoides pteronyssinus.
AB  - House dust mites are the most common cause of allergic sensitization in
      respiratory allergic patients in the world. Tyrophagus putrescentiae (TP), which
      was followed by Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus
      (DP), has been reported as the third most common house mite in Korea. We
      previously reported that many respiratory allergic patients had become
      concomitantly sensitized to DP, DF and TP. The aims of this study were to
      identify the allergic components of TP and to evaluate the cross-reactivity
      between TP and DP. The allergenic components of TP and DP extracts were
      determined with SDS-PAGE and IgE immunoblotting analysis. The cross-reactivity as
      evaluated by ELISA inhibition and inhibitory immunoblotting experiments.
      According the SDS-PAGE, the protein components of the two extracts were somewhat
      different, although a few components displayed identical molecular weights. The
      18 kD protein of TP was the most prevalent allergen in the sera of patients
      sensitized to TP and DP. Both of the maximum inhibition percentages of optic
      densities of TP-specific IgE in ELISA with TP and DP extract were 100%,
      respectively and the 50% inhibitory dose (ID50) of TP extract and DP extract were
      0.01 micrograms/ml and 0.02 micrograms/ml, respectively. Maximum inhibition of
      optic densities of DP-specific IgE in ELISA with TP and DP extracts were 29% and
      100%, respectively and the ID50 of DP extract was 0.007 micrograms/ml. On
      inhibitory immunoblotting of DP specific IgE, 5 micrograms/ml of TP extract
      completely inhibited 16 kD without inhibiting the other allergic component.
      Whereas, on inhibitory immunoblotting of TP-specific IgE, 5 micrograms/ml of DP
      extract completely inhibited all the IgE binding components of TP. These results
      suggested that the major allergen of TP may be the 18 kD component and we also
      concluded that TP allergens have a strong cross-reactivity with DP extracts, but
      that DP allergens only have partial cross-reactivity with TP extracts.

PMID- 9587251
TI  - Hepatitis G virus infection in hemodialysis and continuous ambulatory peritoneal
      dialysis patients.
AB  - To determine the prevalence and clinical relevance of HGV infection in dialysis
      patients, we performed a cross-sectional study of 61 HD patients and 79
      Continuous Ambulatory Peritoneal Dialysis (CAPD) patients. HGV-RNA was identified
      by reverse-transcription (RT) polymerase chain reaction (PCR) assay with primers
      from the 5'-untranslated region of the viral genome. The prevalence of HGV
      infection was similar in HD and CAPD patients (9.8% vs. 12.7%), while that of HCV
      infection was significantly higher in HD patients compared to CAPD patients
      (16.4% vs. 1.3%, p < 0.05). The mean age (49.2 +/- 13.4 vs. 46.7 +/- 13.0 years),
      male to female ratio (2.4:1 vs. 1.3:1), history of transfusion (62.3% vs. 49.4%),
      history of hepatitis (27.9% vs. 26.6%), mean ALT level during the previous 6
      months (22.4 +/- 37.9 vs. 14.0 +/- 7.4 IU/L), and the prevalence of HBsAg (8.2%
      vs. 6.3%) showed no difference between HD and CAPD patients. In both HD and CAPD
      patients, the presence of HGV RNA was not related to age, sex, duration of
      dialysis, history of transfusion, history of hepatitis, or to the presence of HBV
      or HCV markers. There was no significant difference in the clinical and
      biochemical data between patients with isolated HGV infection (n = 12) and
      patients without viremia (n = 106). The clinical feature of patients coinfected
      with HGV and HBV (n = 2), or HGV and HCV (n = 2) seemed to be similar to those of
      patients with isolated HBV (n = 8) or HCV (n = 9) infection. In conclusion, the
      prevalence of HGV infection was not different between HD and CAPD patients, and
      HGV infections did not seem to be associated with clinically significant
      hepatitis. The routes of HGV transmission, other than transfusion or
      contamination during HD procedure, were suspected.

PMID- 9587252
TI  - Clinical and electrophysiological characteristics in Korean patients with WPW
      syndrome.
AB  - This study was designed to investigate the clinical and electrophysiologic
      characteristics of WPW syndromes in Korea. A total of 400 symptomatic WPW
      syndrome patients were consecutively recruited. The most common documented
      symptomatic tachyarrhythmia was orthodromic atrioventricar reentrant tachycardia
      (75.3%), followed by atrial fibrillation (31.3%), and antidromic atrioventricular
      reentrant tachycardia (6.2%). There was a higher incidence of multiple bypass
      tract in patients with antidromic tachycardia than in those with orthodromic
      tachycardia (30.4 vs 4.3%, P < 0.001). The inducibility of tachyarrhythmia with
      electrophysiologic study in this study population was 95.8%. The most frequent
      location of the accessory pathway was the left free wall (48.0%), followed by the
      right free wall (29.1%), posterior septum (17.5%) and anterior septum (3.5%).
      These results indicated that 1) clinical and electrophysiological characteristics
      of Korean patients with WPW syndrome were similar to those of western countries
      and 2) the electrophysiologic study was important in the evaluation of patients
      with WPW syndrome.

PMID- 9587253
TI  - The effects of laminin on the characteristics and differentiation of neuronal
      cells from epidermal growth factor-responsive neuroepithelial cells.
AB  - Many extracellular matrix molecules are expressed in the embryonic nervous system
      and there is some evidence that they are important regulators of neural
      development. Of these molecules, laminin appears to be the most potent, affecting
      virtually all neurons of the peripheral and central nervous system. This study
      was undertaken to investigate the effects of laminin on the proliferation and
      differentiation of cultured neuroepithelial cells taken from fetal rat forebrains
      (embryonic day 17-19). The results are summarized as follows. 1) Neuroepithelial
      cells cultivated in epidermal growth factors containing serum-free medium
      subsequently differentiated into neurons, astrocytes, and oligodendrocytes. 2)
      Neuronal cells derived from neuroepithelial cells were immunoreactive for gamma
      aminobutyric acid (GABA) or substance P, but were not for serotonin and tyrosine
      hydroxylase. 3) In western blot analysis, the phosphorylated neurofilament
      content in neuronal cells was higher in culture on laminin than in culture on
      poly-L-lysine (PLL). 4) The proliferation rate of GABAergic neurons was higher in
      culture on laminin than in culture on PLL. These results suggest that GABAergic
      and substance P-ergic neurons can be differentiated from neuroepithelial cells
      and that laminin promotes the differentiation of neuronal cells from
      neuroepithelial cells and the increased proliferation rate of GABAergic cells.

PMID- 9587254
TI  - Factors affecting transformation efficiency of BCG with a Mycobacterium
      Escherichia coli shuttle vector pYUB18 by electroporation.
AB  - BCG has been one of the vehicles for multi-recombinant vaccine. However, low
      transformation efficiency of BCG with plasmid DNA hampered studies involving
      expression of foreign antigens in BCG. In an effort to determine the optimal
      conditions, this study was initiated to investigate factors involved in the
      transformation of BCG with a Mycobacterium-Escherichia coli shuttle vector,
      pYUB18, by electroporation. Mycobacterium bovis BCG (strain 1173P2) was grown in
      Middlebrook (M) 7H9 broth containing albumin-dextrose-catalase and 0.05% tween
      80, and transformed BCG was grown in M7H10 agar containing kanamycin for counting
      viable cells. Pretreatment of BCG with 10 mM CaCl2 improved the transformation
      efficiency, but overnight incubation of BCG with 1% glycine did not. The
      transformation efficiency in BCG also varied depending on voltage, resistance,
      and DNA concentration. The maximum transformation efficiency was obtained when
      the infinity resistance, 12.5 Kv/cm, and 100 ng of DNA were used, and reached 1.4
      x 10(5) CFU/microgram of plasmid DNA, which is about 3-100 times greater than
      those from previous reports. The transformation conditions described in this
      study, therefore, will give us a better position for employing BCG as a vehicle
      for developing multi-recombinant vaccines.

PMID- 9587255
TI  - Facial nerve schwannomas: CT and MR findings.
AB  - The present study was undertaken to analyze the radiologic findings of
      intratemporal and extratemporal schwannoma (ITS & ETS). We retrospectively
      reviewed the CT (9 cases), MR (3 cases) and medical records of 10 facial
      schwannoma patients. After classifying these into ITS and ETS, radiologic and
      clinical findings were analyzed. The most common clinical manifestations were
      facial nerve dysfunction (6/6 cases, 100%) and hearing impairment (5/6 cases,
      83.3%) in ITS and parotid mass (4/4 cases, 100%) in ETS. Geniculate ganglion (GG)
      was the most commonly involved segment of ITS (5/6 cases, 83.5%). On CT, ITS
      arising in GG (4 cases) showed erosion of the petrous bone (4 cases), cochlea (3
      cases), lateral semicircular canal (1 case) and ossicles (3 cases). ITS arising
      in the mastoid segment (1 case) showed the destruction of the jugular plate and
      external auditory canal wall. All three ITS in which MRI was performed showed iso
      to hypointensity on T1WI, hyperintensity on T2WI and well-enhanced on post
      enhanced T1WI. ETS showed various findings, but all four ETS were located in the
      posterolateral portion of the retromandibular vein and extended toward the
      stylomastoid foramen. In conclusion, ITS shows the schwannoma on MR. ETS shows
      various findings. However, if the tumor is located along the extratemporal facial
      nerve course, then facial schwannoma may be suspected.

PMID- 9587256
TI  - Development and animal study of a pediatric ventricular assist device.
AB  - We have developed a pneumatic type ventricular assist device (VAD) for pediatric
      use and implanted it in six mongrel dogs to study its efficacy and to identify
      any problems. The diaphragm-type blood pump has a stroke volume of 34 cc. The
      ventricle of the blood pump was made from polyurethane to enhance
      antithrombogenesis. The pump was implanted between the left atrium and the
      descending thoracic aorta and it functioned in a fill-to-empty control mode. The
      average pump flow rate was 0.41 L/min when the pump rate was 60 bpm. The duration
      of support ranged from 1 to 26 hours. The hemodynamic effects of the VAD on the
      heart failure model were monitored. An increase in pump flow rate was indicated
      in such a deteriorated heart failure and respiratory failure. Studies to date
      suggest that, with further refinement, a more reliable VAD with clinical
      applications could be developed.

PMID- 9587257
TI  - Serum gastrin and pepsinogen I, II concentrations in children with Helicobacter
      pylori infection: the role of CagA and VacA.
AB  - Serum gastrin and pepsinogen concentrations were measured in 51 children infected
      with Helicobacter pylori, to investigate the clinical significance and influence
      of CagA and VacA on serum concentrations of these peptides. CagA+ was 44/51 (86%)
      and VacA+ was 42/51 (82%). Type I (CagA+/VacA+) included 39/51 (76%), type II
      (CagA-/VacA-) was 4/51 (8%), and intermediate (CagA-/VacA+, CagA+/VacA-) was 8/51
      (16%). There was no significant correlation between endoscopic diagnosis and the
      state of CagA/VacA. Serum gastrin concentrations were not significantly
      correlated with the state of CagA/VacA. Serum pepsinogen I and II concentrations
      were significantly higher in CagA+ than in CagA-, but there was no significant
      difference between VacA+ and VacA-, Serum pepsinogen I/II ratio was not
      significantly correlated with the state of CagA/VacA. There was no significant
      difference between serum concentrations of gastrin, pepsinogen I and H. pylori
      phenotypes. However, pepsinogen II concentration was significantly higher in type
      I than type II. Pepsinogen I/II ratio was significantly lower in type I and
      intermediate than in type II. These findings suggest that CagA positively and
      phenotype of H. pylori could play a role in the development of upper
      gastrointestinal diseases in children.

PMID- 9587258
TI  - Computed numerical analysis of the biomechanical effects on coronary
      atherogenesis using human hemodynamic and dimensional variables.
AB  - The objectives of this investigation were to evaluate biomechanical factors in
      the atherosclerotic process using human in vivo hemodynamic parameters and
      computed numerical simulation qualitatively and quantitatively. The three
      dimensional spatial patterns of steady and pulsatile flows in the left coronary
      artery were simulated, using a finite volume method. Coronary angiogram and
      Doppler ultrasound measurement of the proximal left coronary flow velocity were
      performed in humans. Inlet wave velocity distribution obtained from in vivo data
      of the intravascular Doppler study allowed for input of in vitro numerical
      simulation. Hemodynamic variables, such as flow velocity, pressure and shear
      stress of the left anterior descending coronary bifurcation site were calculated.
      We found that there were spatial fluctuation of flow-velocity and recirculation
      areas at the curved outer wall of the left anterior descending coronary artery,
      which were due to the differences of flow-velocity and shear stress, especially
      during the declaration phase of pulsatile flow. This study suggests that
      rheologic properties may be a part of the atherogenic process in the coronary
      bifurcated and curved areas.

PMID- 9587259
TI  - Acute gastroparesis in Duchenne's muscular dystrophy.
AB  - Duchenne's muscular dystrophy (DMD) is an X-linked recessive disease. Clinical
      descriptions of the disorder focus principally on skeletal muscle degeneration.
      Another manifestation, which involves the gastrointestinal tract, may be fatal.
      But its prevalence remains undefined. We report here a case of acute
      gastroparesis associated with Duchenne's muscular dystrophy. In our case, the
      patient's symptoms were improved by prokinetic agents and timely decompression in
      life-threatening acute gastric dilatation.

PMID- 9587260
TI  - A traumatic pseudoaneurysm of the superficial temporal artery.
AB  - Pseudoaneurysm arising from the superficial temporal artery (STA) is very rare
      and is most commonly caused by blunt trauma. Most pseudoaneurysms of the STA
      usually present as a painless pulsating mass, with concomitant symptoms according
      to location, and their size may rapidly increase. The treatment of choice is
      ligation and resection. We present a case of pseudoaneurysm arising from STA
      after a penetrating injury caused by broken glass. We describe the history,
      findings of physical examination, Doppler sonography, angiography,
      histopathology, and the outcome of treatment. We also include a brief review of
      this condition.

PMID- 9587261
TI  - A case of loiasis.
AB  - The prevalence of Loa loa infections in non-endemic areas such as Korea is very
      low, even though it is quite common in the endemic regions of West and Central
      Africa. We describe a patient who presented with temporary localized edema
      (classical Calabar swellings) after travelling to Cameroon and in whom the
      diagnosis of loiasis was made by ELISA. This is the second reported case of
      loiasis in Korea. As international travel is becoming more frequent, Loa loa
      infection should be considered in the differential diagnosis for patients with
      eosinophilia and Calabar swellings in Korea.

PMID- 9587262
TI  - A close look at the restorative needs of patients with dental implants: Part 2.

PMID- 9587263
TI  - Correcting inaccurate jaw relation records.

PMID- 9587264
TI  - Unleashing creative leadership & teamwork cooperation in your laboratory.

PMID- 9587265
TI  - An analysis of how infection-control research applies to the dental-laboratory
      environment.

PMID- 9587266
TI  - Risks of infection with blood- and saliva-borne pathogens from internally
      contaminated impressions and models.

PMID- 9587268
TI  - Geriatric ceramics: esthetic considerations for the older dentition.

PMID- 9587267
TI  - A close look at the restorative needs of patients with dental implants: Part 1.

PMID- 9587269
TI  - Unleashing creative leadership and teamwork in your laboratory.
AB  - Look for creative problem-solving to improve systems and enhance teamwork.
      Whether a two-person, or a 200-person laboratory, creative leadership and team
      centered philosophy will afford a laboratory a solid foundation and reputation.

PMID- 9587270
TI  - Effect of masticatory cycles on tooth compression and resultant leakage of
      amalgam retrofills.
AB  - This study was carried out to investigate the effect of changes in tooth
      structure due to masticatory cycles on amalgam retrofillings performed to
      different cavity depths. Forty upper maxillary first molars were tested. In the
      obturated palatal root apical amalgam was inserted to different depths (1.5 and 3
      mm). Eight casts were built, each having four sample molars. To block the teeth,
      the vestibular roots were embedded in resin (palatal root was left free). The
      eight remaining retrofilled teeth served as controls and were not submitted to
      occlusal forces. A mechanical device to simulate masticatory cycles subjected the
      teeth to 500,000 to three million cycles. Leakage was assessed from dye
      penetration observations. The values of microleakage were analyzed and compared,
      and strain gauges were used to assess structural modifications to the tooth. The
      leakage of all retrofilled obturations increased in correlation with the number
      of masticatory cycles. At three million cycles, root length compression was 0.3
      +/- 0.02%. Leakage was significantly less for the deeper cavity preparations at
      all stages. This in vitro study suggests a significant effect by root compression
      due to masticatory loads on the leakage of retrofilled amalgam obturations.

PMID- 9587271
TI  - Coronal leakage of obturated root canals after long-term storage using a
      polymicrobial marker.
AB  - This in vitro study investigated the effect of long-term storage on the coronal
      leakage of a microbial marker on teeth root filled with lateral condensation of
      cold gutta-percha and one of two sealers. Sixty single-rooted teeth were prepared
      chemomechanically to a size 40 master apical file. The teeth were divided into
      two groups of 20 teeth each and obturated with gutta-percha using either Apexit
      or Tubliseal EWT sealer. The teeth were stored for 6 months in artificial saliva
      and tested for leakage using a marker consisting of S. sanguis and P. intermedia.
      The teeth were checked for bacterial leakage daily for 90 days. All positive
      control teeth leaked after 24 h, while the negative control teeth remained
      uncontaminated throughout the test period. Leakage reached the apex through the
      experimental teeth at the earliest at 17 days and at latest at 88 days. Fifty
      percent and 70% of the specimens of the Apexit and Tubliseal EWT groups
      respectively showed leakage at 90 days. There was no statistically significant
      difference (p > 0.05) between the two groups.

PMID- 9587272
TI  - Effect of gutta-percha solvents on calcium and phosphorus levels of cut human
      dentin.
AB  - Fresh intact human teeth were cut and treated with 3 commonly used gutta-percha
      solvents: chloroform, xylene, and Endosolv-E. Treatment consisted of embedding
      the specimens of each group for 15 or 30 min in the test solution. After each
      time interval, the specimens were rinsed, dried, and prepared for surface energy
      dispersive spectrometric analysis. The calcium and phosphorus levels in each
      specimen were recorded and the differences between the test groups were
      statistically analyzed. The changes in the calcium and phosphorus levels
      following treatment with the gutta-percha solvents were minimal and statistically
      nonsignificant.

PMID- 9587273
TI  - In vitro antibacterial activity of a glass ionomer endodontic sealer.
AB  - The aim of this study was to evaluate the antibacterial activity of a recently
      introduced glass ionomer endodontic sealer, Ketac Endo (KE), compared to a
      commonly used ZOE-based endodontic sealer, Roth's cement (RC). With the use of E.
      faecalis as a test organism, the agar diffusion test (ADT) and direct contact
      test (DCT) were performed. For the DCT, the sealers were mixed and placed on the
      side wall of microtiter plate wells. A 10 microL bacterial suspension was placed
      on the tested material samples 20 min, 24 h, and 7 days after mixing. Bacteria
      were allowed to directly contact the sealers for 1 h at 37 degrees C. Fresh media
      was then added and bacterial growth was measured every 30 min over 15 h. The
      results showed that in the ADT, freshly mixed KE exhibited a twofold greater
      inhibition zone than RC (p < 0.05); in the DCT, freshly mixed KE and RC
      completely inhibited bacterial growth. The 24-h and 7-day samples of KE showed no
      antibacterial activity, whereas RC continued to exhibit a strong effect with
      similar samples. It has been concluded that KE possesses a short-acting very
      potent and diffusable antibacterial activity, whereas RC extends its effect over
      7 days after setting.

PMID- 9587274
TI  - Occurrence of Prevotella nigrescens and Prevotella intermedia in infections of
      endodontic origin.
AB  - The occurrence of Prevotella intermedia and Prevotella nigrescens in endodontic
      infections was studied using sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) of whole cell protein to distinguish between the
      species. Previous studies have shown an association between black-pigmented
      bacteria (BPB) and endodontic infections and that Prevotella intermedia
      (previously known as Bacteroides intermedius) was the most commonly isolated BPB.
      Recently, however, strains identified as P. intermedia were shown to in fact be
      composed of two separate species, P. intermedia and P. nigrescens. Fifty-six
      strains of BPB isolated from endodontic infections and previously identified as
      P. intermedia were used in this study. Following SDS-PAGE, P. nigrescens showed a
      unique 18.6 kDa band that was used to differentiate P. nigrescens from P.
      intermedia. Of the 56 strains of BPB, 41 (73.2%) were identified as P. nigrescens
      and 15 (26.8%) as P. intermedia. This study confirms that P. nigrescens, and not
      P. intermedia, is the BPB most often isolated from infections of endodontic
      origin.

PMID- 9587275
TI  - In vitro evaluation of effects of ultrasonic root-end preparation on resected
      root surfaces.
AB  - This in vitro study investigated structural alterations in resected roots that
      had root-end preparations made with a conventional microhead handpiece and
      ultrasonics at two intensity levels. Root ends were examined with fluorescence
      confocal microscopy. Serial histologic sections to the 2 mm levels and then at
      the level of 3 mm and 4 mm from the resected surface were examined. Statistical
      analysis of the confocal data indicated no significant difference between the
      groups in the number and length of the fractures. Results of the histologic data
      indicated that root ends prepared by ultrasonics had a statistically greater
      number of fractures than both the control and the conventionally prepared groups.
      The latter did not differ significantly from each other.

PMID- 9587276
TI  - Obturation of root canals in vivo with a new vacuum technique.
AB  - It was demonstrated in vitro that it is possible to achieve obturation of the
      root canal system with a system utilizing a reduced pressure of 15 hPa (15 mbar).
      The purpose of this study was to develop a procedure to reach a vacuum of at
      least 15 hPa within root canals in vivo. It was also determined if root canals
      could be obturated in daily practice with this vacuum technique. After hand
      instrumentation of the root canals a tooth was prepared for obturation of the
      canals with the new technique by obtaining a tightly fitting attachment to a
      vacuum pump. The result showed that it was possible in vivo to reach reduced
      absolute pressures of 10 hPa in roots and to fill the root canal system with the
      new system.

PMID- 9587277
TI  - Effect of two obturation techniques on the filling of lateral canals and the main
      canal.
AB  - The three-dimensional obturation of the root canal system is widely accepted as a
      key factor for successful endodontic therapy. The purpose of this study was to
      evaluate the obturation of lateral canals and the main canal using cold lateral
      condensation versus the gutta-percha coated rigid carrier. Thirty epoxy blocks
      with five lateral canals placed at varying angles from the main canal were used.
      Each experimental group was obturated by a board certified endodontist with
      clinical experience in the respective obturation technique. The length of gutta
      percha and sealer in the lateral canals was measured under a microscope (x30,
      Unitron) to the nearest 0.5 mm. The blocks were sectioned with an Isomet Plus
      precision saw (Buehler, Lake Bluff, IL) and copious water irrigation
      perpendicular to the main canal at the apex, the height of contour, and at 0.8,
      1.6 and 2.4 mm from the canal apex. A microscope (x100, Leitz, Switzerland) was
      used to determine voids. There was significantly (p < .001) more gutta-percha in
      the lateral canals with the gutta-percha coated rigid carrier technique. In
      contrast, the cold lateral condensation technique had significantly (p < .001)
      more sealer in the lateral canals. However, there was no significant (p < .05)
      difference, in gutta-percha-plus-sealer filling of the lateral canals, between
      the two techniques. In the apical 1 mm of the main canal there were significantly
      (p < .011) fewer voids with the gutta-percha coated rigid carrier technique
      compared to the cold lateral condensation. In the model chosen, the gutta-percha
      coated rigid carrier technique and the cold lateral condensation technique were
      equally effective in filling lateral canals. In filling the main canal, however,
      the coated rigid carrier technique was more effective.

PMID- 9587278
TI  - Apical sealing using two thermoplasticized gutta-percha techniques compared with
      lateral condensation.
AB  - This study was conducted to compare the apical sealing capacity of three filling
      techniques, a multiphase gutta-percha obturation technique, JS Quickfill, and
      lateral gutta-percha condensation. A four-stage stepback preparation was executed
      with circumferential filing in a total of 70 recently extracted permanent
      maxillary incisors and canines. Three experimental groups (20 teeth in each
      group) and two control groups (5 teeth in each group) were formed at random. Each
      experimental group was obturated with a different technique. The positive control
      group was not obturated. In the negative control group, the whole root was
      covered with two full nail varnish layers. Teeth were immersed in India ink for
      48 h, demineralized, cleared with methyl salicylate, and examined with a
      stereomicroscope. None of the specimens obturated with the multiphase gutta
      percha obturation system showed any penetration of India ink beyond the end of
      the preparation. In the groups of teeth obturated by JS Quickfill or lateral
      gutta-percha condensation, leakage was detected in one specimen from each group.
      No statistically significant differences were seen among groups. We conclude that
      the newer thermoplasticized filling techniques can be used successfully to
      obturate root canals in large, straight roots.

PMID- 9587279
TI  - Sealing ability of several restorative materials used for repair of lateral root
      perforations.
AB  - Amalgam, IRM, Vitremer, Bisfil, and Ana Norm Liner were evaluated for repair of
      experimentally induced lateral perforations. Eighty-five sound, mandibular, and
      maxillary molars, extracted for periodontal reasons, were selected for this
      study. The sample teeth were randomly divided in five groups with 15 specimens
      each. Ten teeth were used as control groups. After the perforations were filled
      with the above-mentioned materials, the teeth were immersed in a 2% methylene
      blue solution for 48 h, sectioned, and dye penetration was measured. The results
      indicated that Bisfil 2 B provided a significantly better seal than the other
      materials.

PMID- 9587280
TI  - In vivo model for assessing the functional efficacy of endodontic filling
      materials and techniques.
AB  - Endodontic fillings were challenged with bacterial ingress in mandibular
      premolars of 4 beagle dogs. Groups 1, 2, and 3 (n = 9), had canals filled with
      gutta-percha and sealer, gutta-percha alone, and sealer alone, respectively.
      After 2 wk, pulp chambers were inoculated with plaque. Group 4 (n = 9) and group
      5 (n = 5) had canals either filled as in groups 1 to 3 or unfilled, respectively,
      but not inoculated. Group 6 (n = 5) had canals unfilled and inoculated. Teeth
      were radiographed periodically for 14 wk, dogs terminated, and jaw blocks
      retrieved and processed for light microscopic examination. Rarefying osteitis
      appeared in group 6 at 3 wk and in groups 2, 3, and 5 at 11 wk. Periradicular
      inflammation was none, mild, or severe. Occurrence of severe inflammation in
      groups 1 to 6 was 0, 11%, 33%, 0, 60%, and 100%, respectively. Groups 1 to 3
      combined differed significantly from group 4 (repeated-measures ANOVA, p < 0.05).
      This model could be used to assess the functional efficacy of endodontic fillings
      in vivo.

PMID- 9587281
TI  - In vitro study of the effect of sodium hypochlorite and glutaraldehyde on
      substrate adherence capacity of macrophages.
AB  - The purpose of this study was to investigate the in vitro effect of two
      irrigation solutions used in endodontics (5.25% sodium hypochlorite and 1%
      glutaraldehyde) on substrate adherence capacity of macrophages to determine if
      these substances can alter macrophage function. Inflammatory macrophages were
      obtained from Wistar rats and resuspended in RPMI-1640 medium. Substrate
      adherence capacity assays were carried out in Eppendorf tubes for 15 min of
      incubation at 37 degrees C in a humidified atmosphere of 5% CO2. The adherence
      index was calculated. Results showed that both sodium hypochlorite and
      glutaraldehyde significantly decreased the substrate adherence capacity of
      inflammatory macrophages. To take into account that adhesion is the first step in
      the phagocytic process of macrophages and in antigen presentation, sodium
      hypochlorite and glutaraldehyde could inhibit macrophage function and reduce
      inflammatory reactions in periapical tissues when they are used in root-canal
      therapy.

PMID- 9587282
TI  - Glycoproteins expression in apical pathologic tissues: clinical incidences.
AB  - Indirect immunofluorescence was used for the localization of the primary
      collagens, fibronectin and laminin. Specimens were extracted from untreated teeth
      with periapical lesions from patients 20 to 30 years of age. An histological
      examination enabled the differentiation of granulomas and cysts, and 5 microns
      sections were used for the indirect immunofluorescence procedure. Antibodies
      against Type I, Type III, and Type V collagen and for fibronectin and laminin
      were obtained from glycoproteins of human cells. The antibody against Type IV
      collagen was prepared from Type IV collagen of beef retina. All the glycoproteins
      investigated were expressed in apical lesions. The intensity of the
      immunostaining appeared more positive at the external area compared with the
      center of the lesion. The type IV collagen was specific for the basement membrane
      of cysts. The immunofluorescence reactions of fibronectin and of laminin were
      similar in intensity in both granulomas and cysts.

PMID- 9587283
TI  - Electron microscopic study on nerve terminals during dentin bridge formation
      after pulpotomy in dog teeth.
AB  - This study was designed to examine the relation between pulpal nerves and the
      differentiation of pulpal cells into preodontoblasts and odontoblasts during the
      healing process after pulpotomy. A total of 36 upper and lower teeth obtained
      from six adult dogs were used. The pulp chamber was opened with a sterile diamond
      bur, the coronal pulp was exposed, and the whole surface of the amputated pulp
      was capped with calcium hydroxide. The interval between pulpotomy and extraction
      was 5, 7, 10, 15, 20, 30, 40, 50, and 60 days, and then specimens were examined
      ultrastructurally. Close contact between fibroblast-like cells/osteoblast-like
      cells and nerve terminals at the calcification front was observed in the early
      healing process after pulpotomy, suggesting a close relation between nerve fibers
      and pulpal cell differentiation.

PMID- 9587284
TI  - In vitro evaluation of the cytotoxicity of two glass-ionomer root canal sealers.
AB  - The cytotoxicity of two glass-ionomer root canal sealers (Ketac-Endo and Endion)
      was tested by using an established cell line, BHK21/C13. Under aseptic
      conditions, the sealers were prepared according to the manufacturers' directions,
      and 0.1 ml of each material was placed in petri dishes. After setting for 6 h,
      the sealers were covered with 20 x 10(4) cells per dish. The cultures were
      incubated at 37 degrees C for 24 h, 48 h, and 72 h. Cytotoxicity was assessed by
      a quantitative technique at three observation periods. Endion was highly
      cytotoxic, causing a significant decrease in cell density. Ketac-Endo proved to
      be a very biocompatible material.

PMID- 9587285
TI  - Evaluation of lidocaine in human inferior alveolar nerve block.
AB  - The purpose of this study was to measure the degree of anesthesia following the
      administration of 3.6 ml of 2% lidocaine solutions with either 1:50,000,
      1:80,000, or 1:100,000 for inferior alveolar nerve block and to compare the
      results with those obtained following the administration of 1.8 ml of the same
      solutions (1). With the use of a repeated measures design, 30 subjects randomly
      received an inferior alveolar injection at three successive appointments. The
      first molar, first premolar, lateral incisor, and contralateral canine (control)
      were blindly tested with an Analytic Technology pulp tester at 3-min cycles for
      50 min. The degree of anesthesia was comparable for the three solutions following
      the administration of 3.6 ml of each solution. Retrospective evaluation showed
      that the volume of the solution influenced the degree of anesthesia.

PMID- 9587286
TI  - Dimensional stability of thermosensitive gutta-percha.
AB  - The expansion and shrinkage of four commercial brands of endodontic
      thermosensitive gutta-percha were evaluated. A modified volume dilatometry
      technique was used; the dilatometric system (DS) consisted of Pyrex glass
      capillary tubes and a specimen chamber. Each sample was weighed to 10(-4) mg,
      placed in the specimen chamber, and subjected to vacuum for 45 min to eliminate
      moisture or gases. The DS was gradually heated from 24 degrees C to 80 degrees C
      and then cooled to 24 degrees C using a well-agitated temperature-controlled
      water bath. In a parallel set of experiments, the DS was heated in the same
      manner but cooled to body temperature (37 degrees C) in the water bath and the
      temperature kept stable at 37 degrees C for 24 h. The level of the mercury
      meniscus within the DS was monitored to determine the percent volume change of
      each sample at 2 degrees C intervals. All samples expanded as the temperature was
      elevated and shrank during cooling. The percent volume change for each of the
      four gutta-percha products, as the temperature was raised to 80 degrees C, ranged
      from an expansion of +11.62 to +12.25. As the temperature was lowered from 80
      degrees C to 24 degrees C, the percent volume change representing shrinkage
      ranged from -2.22 to -3.53. When the temperature was lowered from 80 degrees C to
      37 degrees C, the products continued to exhibit shrinkage for a range of time
      between 45 min and 10 h before stabilizing at a fixed volume. The final percent
      volume change for each experiment, with each product, was positive, ranging from
      +5.50 to +7.20, with discernible differences between products.

PMID- 9587287
TI  - An evaluation of the bactericidal effect of the Nd:YAP laser.
AB  - The aim of this in vitro study was to compare the efficacy of a classical
      irrigant with that of a laser in disinfecting a contaminated root canal. Thirty
      canals of extracted single-root teeth were prepared with files to size #20. The
      teeth were sterilized with Germispad (Spad, France) for 30 min and then
      inoculated with Streptococcus mitis ATCC 33399. By randomization, the teeth were
      divided into six groups of five teeth each. In the first group, teeth were
      neither inoculated nor prepared. This was the sterility control group (1). In the
      second group (2) teeth were inoculated without any preparation: as positive
      controls. The third group was inoculated and then hand-instrumented with files to
      size #30 with 5.25% NaOCl as irrigant. This was the hand instrumentation group.
      The other groups were prepared with hand instrumentation with files to size #30,
      using sterile water as an irrigant, and the canal was then lased with different
      frequencies as follows: group 4, frequency of 5 Hz and power of 260 mJ; group 5,
      frequency of 10 Hz and power of 310 mJ; and group 6, frequency of 30 Hz and power
      of 300 mJ. After experimentation, the residual colonies were counted. The results
      indicated that (i) the treatment with NaOCl and manual instrumentation
      effectively inhibited the growth of Streptococcus mitis ATCC 33399; and (ii) the
      antibacterial effect of the Nd:YAP laser depended on the frequency. Only a
      frequency of 30 Hz of the Nd:YAP laser inhibited the growth of Streptococcus
      mitis ATCC 333999.

PMID- 9587288
TI  - Incidence of Lightspeed separation and the potential for bypassing.
AB  - It is important for endodontic instruments to have a low fracture rate. If a
      fracture does occur, it would be desirable to have the ability to bypass the
      broken segment and complete the root canal treatment. One hundred sixty-two root
      canals in 52 maxillary and mandibular first molars were cleaned and shaped with
      Lightspeed instruments by three endodontists in their private practices. The
      canals were instrumented using the technique recommended by the manufacturer. All
      canals were instrumented to at least a size 45 at the working length. Six
      instruments separated during treatment. All six had been used more times than
      recommended by the manufacturer. Five of the six were easily bypassed and
      treatment completed.

PMID- 9587289
TI  - An in vitro study of furcation perforation repair using calcium phosphate cement.
AB  - Furcation perforations created in the pulpal floors of 30 extracted human molars
      were repaired with either light-cured glass ionomer cement (GI), calcium
      phosphate cement (CPC), or light-cured glass ionomer cement placed over a CPC
      matrix (M). After the cement was set, the teeth were immersed in India Ink for 48
      h, dried, and sectioned longitudinally. Dye penetration into the furcation repair
      was independently evaluated by three board-certified endodontists. There was no
      significant difference in the mean extent of dye leakage among the three
      experimental groups. The use of CPC, with its enhanced biocompatibility,
      potential for osteoconduction, and sealing ability, may improve the prognosis of
      teeth with furcation perforations.

PMID- 9587290
TI  - Cutaneous sinus tract caused by vertical root fracture.
AB  - This report presents a rare case of odontogenic cutaneous sinus tract caused by a
      vertical root fracture. The root-fractured molar was probably caused by an
      accidental blow by a cow 3 years ago. Despite all treatments by physicians and
      surgeons for nearly 1 year, the sinus tract recurred repeatedly. After diagnosis
      and extraction of the fractured molar by the dentist, the sinus tract healed
      uneventfully in a month.

PMID- 9587291
TI  - In vitro release of hydroxyl ions from six types of calcium hydroxide nonsetting
      pastes.
AB  - The role of intracanal medication in root canal treatment is very important.
      Calcium hydroxide (Ca(OH)2) is considered to fulfill many of the properties of an
      ideal root canal dressing mainly due to its alkalizing pH. It is bacteriocidal
      and neutralizing to the remaining tissue debris in the root canal(s) and through
      the continuous release of OH- ions it promotes an alkalizing osteogenic
      environment for the surrounding tissues. The purpose of this study was to examine
      the pH values of various Ca(OH)2 based on compounds used as intracanal
      medicaments over a period of 5 days. The following materials were tested:
      Calasept, Calcicur, Calxyl blue, Calxyl red, Reogan rapid, and Tempcanal. After a
      fast OH- release period (2 h) each compound reached an asymptotic pH state. The
      results showed that all materials exhibited alkalizing pH with Reogan rapid,
      Calxyl Red, and Calcicur being the most potent (p = 0.05). The final pH of each
      compound correlated positively with the Ca(OH)2 mass fraction contained in it.

PMID- 9587292
TI  - Effects of local anesthesia on substance P and CGRP content of the human dental
      pulp.
AB  - The aim of the study was to determine immunoreactive Substance P (iSP) and
      immunoreactive calcitonin gene-related peptide (iCGRP) content in the human
      dental pulp and whether local anesthesia has an effect on the neuropeptide
      content. Dental pulps were obtained from patients, who underwent surgical
      extraction of all 4 impacted wisdom teeth under general isoflurane gas
      anesthesia. There was a very high interindividual variation in tissue content,
      with small variation in levels found in teeth from the same patient. Pulps
      obtained from lower teeth without local anesthesia contained an average of 131 +/
      62 fmol/mg protein of iCGRP and 15 +/- 9 fmol/mg iSP (n = 10). With additional
      mandibular block anesthesia the values were 194 +/- 71 fmol/mg iCGRP
      (statistically significant, p = 0.0356, Mann-Whitney-rank-sum-test) and 12 +/-
      3.6 fmol/mg iSP. The results suggest that local anesthesia attenuates
      neuropeptide release in the human dental pulp during surgical extraction.

PMID- 9587293
TI  - Oral bone loss is increased in ovariectomized rats.
AB  - Alveolar bone loss associated with periodontal disease occurs frequently in
      postmenopausal females, the same group that is predisposed to osteoporosis. To
      determine if the estrogen-deficient state enhances oral bone loss, we studied
      ovariectomized rats administered the potent bone-resorbing cytokine interleukin-1
      or the periodontal pathogen Campylobacter rectus lipopolysaccharide (LPS). Distal
      root canals of first mandibular molars were instrumented with endodontic files,
      and bone resorbing factors were deposited and sealed into the root canal.
      Radiographs of periapical bone loss were evaluated using computer assisted image
      analysis to determine lesion size. Both interleukin-1 and C. rectus LPS caused a
      significant increase in lesion area in both ovariectomized and normal rats when
      compared with controls and a significant increase in ovariectomized animals
      compared to nonovariectomized animals receiving LPS. Using this endodontic model,
      we have demonstrated that estrogen deficiency results in increased oral bone loss
      in rats.

PMID- 9587294
TI  - Scanning electron microscopic evaluation of finishing techniques on IRM and EBA
      retrofillings.
AB  - Various techniques have been advocated for finishing retrofilling materials. This
      study evaluated marginal interfaces between tooth structure and the retrofilling
      material following three techniques of finishing IRM and EBA. This interface was
      evaluated for the presence of flash and for adaptation to the prepared canal
      walls. Thirty-one teeth were divided into six groups of five and one control. The
      teeth were instrumented to a minimum of a 35 K-file, obturated with gutta-percha,
      resected perpendicular to their long axes and ultrasonically prepared to receive
      a retrofilling. The teeth were filled with either IRM or EBA cement and finished
      by ball burnishing, burnishing with a moistened cotton pellet, or with a carbide
      finishing bur in a high-speed handpiece with air/water spray. Photomicrographs
      were made and examined by four evaluators. Retrofillings finished with a
      finishing bur displayed significantly better marginal adaptation and little
      evidence of flash when compared to the other techniques (p < 0.05). There were no
      significant differences between ball burnished or moistened cotton pellet
      techniques or between retrofilling materials used in this study (p < 0.05).

PMID- 9587295
TI  - Calcium hydroxide root canal sealers--histopathologic evaluation of apical and
      periapical repair after endodontic treatment.
AB  - Eighty root canals of the premolars of 4 dogs, with vital pulp, were instrumented
      and filled during the same session with the Sealapex, CRCS, Sealer 26, and Apexit
      sealers. The animals were sacrificed 180 days after root canal filling and their
      maxillae and mandibles were removed and fixed in 10% formalin. After routine
      histologic processing, the sections were stained with hematoxylin-eosin and
      Mallory trichrome. Histopathologic analysis showed that Sealapex was the sealer
      that best permitted the deposition of mineralized tissue at the apical level and
      was the only sealer that provided complete sealing (37.5% of cases). With the use
      of Sealapex, no inflammatory infiltrate occurred and there was no reabsorption of
      mineralized tissues. In contrast, partial sealing and a moderate inflammatory
      infiltrate occurred with the use of CRCS. When Apexit and Sealer 26 were used the
      absence of sealing was frequent and active reabsorption of mineralized tissues
      occurred in most cases. The inflammatory infiltrate predominating with the use of
      Apexit was of the severe type, whereas with the use of Sealer 26 the inflammatory
      infiltrate was mild or absent.

PMID- 9587296
TI  - The use of a 16s rDNA directed PCR for the detection of endodontopathogenic
      bacteria.
AB  - The study evaluates a 16S rDNA directed polymerase chain reaction (PCR) to detect
      and differentiate bacteria in necrotic root canal samples. The examination
      focused on species that are fastidious concerning culture or are difficult to
      differentiate after culturing by biochemical methods. In the described PCR assay,
      a universal 16S rDNA directed forward primer in combination with a highly
      specific reversed one was used to amplify taxon specific gene fragments of 230 to
      950 bp length. A similar PCR reaction using a universal 16S rDNA reversed primer
      was also established to demonstrate bacteria in root canal specimens in general.
      A first application of this method revealed the presence of Actinomycetales
      species, Fusobacterium nucleatum, "Streptococcus milleri," and, presumably for
      the first time described in infected root canals, Bacteroides forsythus. The
      identity of amplificons was confirmed by generating sequence information and
      comparison to gene databanks.

PMID- 9587298
TI  - Microleakage of a new and an old Kerr root canal sealers.
AB  - This study sought to evaluate the microleakage of two Kerr root canal sealers
      (old and new formulas of the Pulp Canal Sealer). Sixty anterior teeth were used.
      After cleaning and shaping to a size 30 file, the teeth were obturated with the
      vertical condensation of gutta-percha with either the old or the new root canal
      sealer. Apical microleakage was determined using pressurized fluid filtration at
      90 min, 1 day, and 1, 4, 12, 18, and 24 wk after root canal obturation. The
      results showed that leakage tended to increase over time for the two groups.
      Also, no significant difference was found in microleakage between the old and the
      new formulas of the root canal sealer.

PMID- 9587297
TI  - Disintegration of endodontic cements in water.
AB  - The disintegration of three endodontic cements in water was determined
      quantitatively and qualitatively. The materials studied were Ketac-Endo (KE),
      Tubli Seal (TS), and AH26 (AH). Specimens were immersed in water for 48 h (GI), 7
      (GII) and 45 days (GIII). The solid residue was then determined. For the
      qualitative analysis three groups of tubes were filled with the materials and
      stored in water for the same periods. The exposed surface was photographed.
      Results expressed as percentage of original mass in the quantitative analysis for
      loss of mass due to dissolution were: GI = KE 2.39 (0.70); TS 3.56 (0.37); AH
      4.94 (2.83); GII = KE 2.84 (0.30); TS 2.50 (0.50); AH 0.66 (0.26); GIII = KE 1.60
      (0.84); TS 1.03 (0.42); AH 1.22 (0.54). Tukey's least significant difference
      (0.05) was 2.94. In the qualitative experiment KE disintegration was far more
      evident than that suffered by other materials. The quantitative results had no
      correlation with the qualitative observations probably due to the difference in
      the moment when the materials were immersed.

PMID- 9587299
TI  - Calcium hydroxide inhibits substrate adherence capacity of macrophages.
AB  - The purpose of this study was to investigate the effect of calcium hydroxide on
      substrate adherence capacity of rat inflammatory macrophages to determine if
      calcium hydroxide can alter macrophage function. Inflammatory macrophages were
      obtained from Wistar rats and resuspended in RPMI-1640 medium. Substrate
      adherence capacity assays were carried out in Eppendorf tubes for 15 min of
      incubation at 37 degrees C in a humidified atmosphere of 5% CO2. The adherence
      index (AI) was calculated. Results showed that calcium hydroxide decreased
      substrate adherence capacity of inflammatory macrophages in a time and dose
      dependent manner. The lowest calcium hydroxide concentration that caused a
      significant inhibition of AI was 1 mM (p < 0.05), and the concentration of
      calcium hydroxide that caused half-maximal inhibition (IC50) was 1.54 mM (p <
      0.01). We conclude that calcium hydroxide decreased substrate adherence capacity
      of macrophages. When adhesion as the first step in the phagocytic process and in
      antigen presentation is taken into account, calcium hydroxide could inhibit
      macrophage function and reduce inflammatory reactions in periapical tissues or in
      dental pulp when it is used in root-canals therapy or in direct pulp capping and
      pulpotomy, respectively. Moreover, this effect could explain, at least in part,
      the mineralized tissue-inducing property of calcium hydroxide.

PMID- 9587300
TI  - Comparison of ultrasonic and high-speed-bur root-end preparations using
      bilaterally matched teeth.
AB  - The purpose of this study was to compare ultrasonic and high-speed-bur root-end
      preparations. Seventy-six roots from 29 bilaterally matched pairs of human teeth
      in cadavers were used in this study. In group 1 ultrasonic preparations were made
      in 38 roots and filled with amalgam. In group 2 high-speed bur preparations were
      made in 38 roots and filled with amalgam. The size of the bony crypt was measured
      and the teeth were extracted and radiographed mesial-distally and buccal
      lingually. None of the root-end preparations resulted in root perforation. The
      mean mesial-distal minimum depth of ultrasonic and high-speed bur preparations
      were 2.11 mm and 1.39 mm, respectively. The mean buccal-lingual minimum depth of
      preparation was 2.51 mm for the ultrasonic and 2.05 mm for the high-speed bur
      preparations. The depth of the ultrasonic preparations was significantly greater
      for both measurements. A significantly greater bevel angle was associated with
      the bur preparations, 35.1 degrees versus 16.0 degrees for the ultrasonic
      preparations. The incidence of ultrasonic root-end preparations deviating from
      the uninstrumented canal spaces was found to be 2.6%. All bur root-end
      preparations were at an acute angle to the long axis of the root. The bony crypt
      size for bur preparations was significantly greater than that for ultrasonic
      preparations.

PMID- 9587301
TI  - Frequency of endodontic treatment in Kuwait: radiographic evaluation of 846
      endodontically treated teeth.
AB  - A retrospective study was conducted to evaluate the radiographic films of 846
      endodontically treated teeth at Benied Al Ghar Dental Center in Kuwait. The most
      frequently treated tooth was the mandibular first molar (17.4%). The number,
      percentage, and distribution of the roots, root canals, and apical foramina were
      reported by individual tooth. The clinical findings were compared to the results
      of previously related in vitro and in vivo studies.

PMID- 9587302
TI  - Infection-related mental and inferior alveolar nerve paresthesia: literature
      review and presentation of two cases.
AB  - A review of the literature on infection-related mental and inferior alveolar
      nerve paresthesia is given. This is followed by 2 case reports. The first case is
      of a mandibular left second molar in which a chloropercha overfill puff occurred
      in the vicinity of the inferior alveolar canal. The tooth remained asymptomatic
      until 2 and 1/2 yr later, when the periapical lesion enlarged and swelling, pain,
      and paresthesia developed. The paresthesia resolved 2 weeks following periapical
      surgery. The second case is of a mandibular right first premolar in which
      paresthesia began 1 day after the initial endodontic treatment. The intracanal
      medication was formocresol on a cotton pellet that was squeezed dry. The
      paresthesia was treated by irrigation, antibiotics, and dexamethasone. The
      paresthesia lasted 7 weeks, and when it resolved the root canal was filled with
      gutta-percha/eucapercha. Almost 9 months later, the tooth remained asymptomatic.

PMID- 9587303
TI  - 3H proline uptake in the tubular compartment of dentin in the rat molar.
AB  - With the use of conventional autoradiographic techniques, it was demonstrated
      that dentin captures 3H proline in significantly greater amounts (p < 0.0002)
      than sclerotic dentin or alveolar bone. Histological observation and the absence
      of capture by sclerosed dentin indicated that this capture occurs within the
      tubular compartment of dentin. It is suggested that this capture reflects the
      deposition of collagen in this compartment. An increase in 3H proline capture
      occurs in dentin affected by cavity preparation (p < 0.0001). This increase in
      capture, on the basis of electron microscopic observation, could not be linked to
      an increase of collagen deposition in affected tubules.

PMID- 9587304
TI  - The disintegration of superEBA cement in solutions with adjusted pH and
      osmolarity.
AB  - This study determined the disintegration of fast-set SuperEBA cement using
      ANSI/ADA Specification No. 30 (Spec #30) as well as modifications in pH,
      osmolarity, time before immersion, and duration of immersion that mimic the
      clinical, endodontic application of this material. After immersion intervals of
      24 h, 1 wk, 1 m, 3 m, or 6 m, specimens were desiccated and weighed. The
      preimmersion and postdehydration weights were obtained to the nearest 1.0 mg and
      the percent weight loss from preimmersion levels was calculated. Adjusting the
      osmolarity to the physiologic level of 300 mOsm/kg resulted in significantly less
      weight loss (p < 0.05) than the control group in distilled water (no modification
      of Spec #30). The pH of the storage solution was found to be a significant factor
      in weight loss. As the acidity and the time of immersion increased, the weight
      loss also significantly increased with the greatest weight loss of 19.81% at pH
      5.5 after 6 m storage. Immersion within 10 min of mixing was not significantly
      different (p > 0.05) in weight from the control of 1 h set-time. The 24 h weight
      loss measurements for the pHs of 5.5 and 6.4 were greater than the 1.5% allowed
      by Spec #30. All other 24 h measurements were less than the 1.5%.

PMID- 9587305
TI  - Study of the Nd:YAP laser. Effect on canal cleanliness.
AB  - The aim of this study was to evaluate the canal cleanliness achieved by five
      different preparation techniques, including use of the laser. By randomization,
      the palatal roots of 50 maxillary molars were assigned to one of five groups.
      During all preparations, a sodium hypochlorite irrigant was used. The following
      techniques were studied: (A) manual instrumentation (serial preparation), (B)
      laser preparation (Nd:YAP laser), (C) manual preparation with laser as adjunct,
      (D) manual preparation with a subsonic device as adjunct (MM 3000 with shapers),
      and (E) manual instrumentation with a subsonic device and laser as adjuncts (MM
      3000 with shapers, Nd:YAP laser). The canal wall surfaces were examined under a
      scanning electron microscope at all levels with a new method using grid
      incrustation on the microscope screen. Techniques A and C differed from each
      other only by the size of the debris particles, which were smaller for the C
      preparation. For laser preparation (B) there was little increase in canal
      diameter increase, and a substantial amount of debris was present. The
      differences between techniques A, C, and D were not significant. The use of the
      subsonic device and laser together as adjuncts (E) showed the cleanest
      preparation with very little debris, opened tubules, and very small particle
      size. This result suggests that the laser has a potential in ensuring optimal
      canal cleanliness.

PMID- 9587306
TI  - Comparison of various transport media on human periodontal ligament cell
      viability.
AB  - The purpose of this study was to determine the ability of various solutions to
      maintain human periodontal ligament cell (PDL) viability in vitro. PDL cells were
      obtained from extracted third molars and premolars of healthy individuals. These
      cells were placed into 24-well culture plates containing milk, Save-A-Tooth, Save
      A-Tooth supplemented with platelet-derived growth factor-BB (PDGF), or Gatorade
      at a concentration of approximately 80,000/well. Cells left dry served as
      negative controls, and cells placed in Eagles' Minimal Essential Medium served as
      positive controls. At 1, 2, 4, 8, and 12 h, cell viability was evaluated using an
      MTS assay and an ELISA plate reader to determine optical density. ANOVA and
      Student-Newman-Keuls tests indicated that milk and Save-A-Tooth with PDGF are
      suitable as transport medium for avulsed teeth and that the addition of PDGF to
      Save-A-Tooth may enhance its ability to maintain PDL cell viability. They also
      suggests that Gatorade would be unsuitable as a transport medium.

PMID- 9587307
TI  - SEM examination of secondary dentine under and opposite cervical carious lesions.
AB  - The deposition of calcified secondary dentine underlying carious lesions and on
      the wall opposite to the carious lesions was examined in this study. Twenty
      single rooted human teeth were used in this work. The teeth were cleaned and
      fractured into two longitudinal halves, which were examined under a scanning
      microscope. The results showed complete disappearance of the dentinal tubules,
      globular mineralized deposits, and mineralized deposits of fibrous morphology
      underlying carious lesions, while on the dentinal walls opposite to the carious
      lesions were calsospherites, mineralized secondary dentine, and typical
      deposition of secondary dentine.

PMID- 9587308
TI  - Comparison of dentinal crack incidence and of post removal time resulting from
      post removal by ultrasonic or mechanical force.
AB  - The purpose of this study was to compare the frequency of canal and intradentin
      cracks after intraradicular post removal using ultrasonic instrumentation or the
      Gonan post removal system. Sixty cadaver teeth were divided into 4 groups of 15
      teeth each: group 1, ultrasonic removal; group 2, Gonan post removal system;
      group 3, cemented posts not removed; and group 4, no posts. Groups 1 and 2 were
      contralateral matched pairs. Para Posts were placed in groups 1, 2, and 3 to 7 mm
      apical to the cementoenamel junction and luted with ZnPO4 cement. The time
      required for post removal in groups 1 and 2 was recorded. The teeth were
      extracted, sectioned, and examined. Canal and intradentin cracks were mapped, and
      their frequency was recorded at each level. There were statistically more cracks
      present in the ultrasonic group than the no post group. There were no other
      differences that reached statistical significance. It took significantly longer
      for post removal using the ultrasonic tip versus the Gonan system.

PMID- 9587309
TI  - Determination of periodontal ligament cell viability in the oral rehydration
      fluid Gatorade and milks of varying fat content.
AB  - The purpose of this study was twofold: 1) to determine if the oral rehydration
      fluid Gatorade could serve as a suitable temporary storage medium for maintenance
      of periodontal ligament (PDL) cell viability on avulsed teeth and 2) to determine
      if fat content is related to maintenance of cell viability when milk is used as
      the temporary storage medium. PDL cells were cultured from extracted human teeth
      then incubated over timed intervals from 15 to 210 min in the oral rehydration
      fluid Gatorade, milks of varying fat content, and saliva. Dulbeco's Modified
      Eagles Medium served as the positive control while tap water served as the
      negative control. Cell viability was determined using a colorimetric assay that
      used Cell Proliferation Reagent WST-1. Results using Gatorade yielded cell
      viability data similar to the negative control, tap water, indicating that this
      oral rehydration fluid was not suitable as a temporary storage medium for the
      avulsed tooth. However, the fat content of milk was found to have an effect on
      cell viability, suggesting that milks with lower fat content may be more
      appropriate for maintaining PDL cell viability than milks with higher fat
      content.

PMID- 9587310
TI  - Sealing depth of Nd:YAG laser on human dentinal tubules.
AB  - Dentin permeability and hypersensitivity are both reduced when the dentinal
      tubules are occluded. Previous scanning electron microscopic studies showed that
      Nd:YAG laser could cause melting of dentin and closure of exposed dentinal
      tubules without dentin surface cracking. Therefore, the aim of the present study
      was to evaluate the sealing depth of Nd:YAG laser on human dentinal tubules.
      Thirty-six dentin specimens with exposed dentinal tubule orifices were used in
      this study. Samples were randomly divided into three groups. Groups A and B were
      lased by Nd:YAG laser at energy of 30 mJ with 10 pulses/s for a stroke along the
      dentin surface. Group C was not lased and served as a control. Subsequently,
      group B was frozen in liquid nitrogen and split by a sharp chisel. Under SEM
      observation, nonlased specimens showed numerous exposed dentinal tubule orifices,
      and lased specimens showed melting of dentin and closure of exposed dentinal
      tubule orifices. The sealing depth of Nd:YAG laser on human dentinal tubules was
      approximately 4 microns.

PMID- 9587311
TI  - Effect of intended treatment on anxiety and on reaction to electric pulp
      stimulation in dental patients.
AB  - Fear and anxiety are common emotional concomitants of acute pain that increase
      the perception of noxious events as painful. In the present study, 92 patients
      who were about to undergo various dental treatments (calculus removal, filling,
      root canal treatment, and extraction) were evaluated comparing the level of their
      dental anxiety and pain expectation from the intended treatment to their reaction
      to electric pulp stimulation. The data indicate that patients differ
      significantly in their dental anxiety levels and in their expectation to
      experience pain according to the following hierarchy (in descending order):
      extraction, root canal treatment, filling, and calculus removal. Anxiety and
      amount of pain expected from treatment correlated significantly with each other,
      but no simple correlations were found between anxiety and actual pain measures
      recorded after pulp stimulation.

PMID- 9587312
TI  - Shaping ability of Lightspeed rotary nickel-titanium instruments in simulated
      root canals. Part 1.
AB  - The aim of this study was to determine the shaping ability of Lightspeed nickel
      titanium rotary instruments in simulated canals. Forty canals consisting of four
      different shapes in terms of angle and position of curvature were prepared by
      Lightspeed instruments using the technique recommended by the manufacturer. This
      report describes the efficacy of the instruments in terms of preparation time,
      instrument failure, canal blockages, loss of canal length, and three-dimensional
      canal form. Overall, the mean preparation time for all canals was 8.12 min with
      canal shape having no significant effect on the speed of preparation. No
      instruments deformed or separated during the study, and none of the canals became
      blocked with debris. Seventeen canals retained their original working length, but
      16 gained in length and 7 lost length. There was no significant difference
      between the canal shapes in terms of the mean loss of distance or category of
      distance change. Apical stops as judged from intracanal impressions were present
      in 23 of the canals but they were all judged to be of poor quality. The canals
      were found to be smooth in the apical half of the canal in 36 specimens and in
      the coronal half of 24 specimens. All the canals had poor taper characteristics,
      and only 16 specimens showed good flow characteristics. Under the conditions of
      this study, Lightspeed instruments prepared canals rapidly, with no fractures,
      canal blockages, and with minimal change in working length. The three dimensional
      form of the canals was compromised as flow and taper were less than ideal,
      presumably as a result of an ineffective stepback procedure. The results imply
      that either the stepback sequence should be modified or another instrument with
      increased taper should be used to refine the canal walls before obturation.

PMID- 9587313
TI  - A comparison of thermoplastic obturation techniques: adaptation to the canal
      walls.
AB  - The purpose of this study was to directly compare the ability of the three types
      of Thermafil obturators, the Obtura II thermoplasticized injectable technique,
      and the lateral condensation technique to obturate a standardized root canal. A
      split-tooth model was constructed and the root canal was obturated 20 times with
      each technique. The quality of each obturation was graded according to
      established criteria of adaptation. Statistical analysis of the results indicated
      that all the techniques were significantly different from each other (p < 0.0001)
      except for the plastic and titanium Thermafil groups (p > 0.05), which were
      similar. Based on the evaluated criteria, the Obtura II injectable technique
      demonstrated the best adaptation to the prepared root canal. This group was
      followed in order by the plastic and titanium Thermafil obturators, the stainless
      steel Thermafil obturators, and finally by the lateral condensation technique.

PMID- 9587314
TI  - A maxillary first molar with two disto-buccal root canals.

PMID- 9587315
TI  - Root canal system of the mandibular incisor.
AB  - To better assess the efficiency of the mechanical preparation of root canals,
      1085 transparent specimens of extracted mandibular incisors were examined for
      canal configuration, thickness and curvature of the root canals, condition of any
      accessory canals, and location of the apical foramen. Greater than 85% of the
      root canals possessed a single canal (Type I). Of specimens in which furcation
      was observed, only 3% possessed two separate canals (Type III and IV). Fewer than
      30% of the specimens showed accessory canals that were mechanically impossible to
      clean. The majority of the lateral branches were small, greater than 80% of the
      specimens were smaller than a #15 reamer, and none of the branches were larger
      than a #30 reamer. Although apical foramina located distal to the apex were
      observed in about 50% of the specimens, 83.6% of all apical foramina were within
      0.5 mm of the apex, and 99.5% were within 1.0 mm. Data on the thickness of the
      root and main canal in the apical portion and curvature of the root canal suggest
      that for adequate apical preparation, a #40 reamer must be able to reach the
      apical constriction.

PMID- 9587316
TI  - Human pulp cells respond to calcitonin gene-related peptide in vitro.
AB  - Cell monolayers derived from human pulpal explants were passaged 3 to 4 times
      before characterization of the response of the cells to calcitonin gene-related
      peptide (CGRP). Northern blot analysis of mRNA revealed the presence of
      transcripts for bone morphogenetic protein-2 (BMP-2). Stimulation with CGRP
      produced a 1.8-fold increase in BMP-2 mRNA expression by the cells. Analysis of
      binding of CGRP to whole cells indicated that unlabeled human CGRP competed with
      labeled CGRP in a dose dependent fashion with a KD, estimated from the EC50, in
      the range of 5 x 10(-8)M. Binding of labeled CGRP was greatly reduced by the
      presence of 10(-6)M CGRP but was unaffected by the presence of 10(-6)M Human
      PTH(1-34) or 10(-6)M calcitonin. CGRP produced a 2.8-fold increase in cyclic AMP
      over basal levels, which was similar to the increase produced by PTH(1-34) (2.6
      fold) but slightly more than the increase produced by calcitonin (1.9 fold). The
      pulp-derived cells displayed a high basal level of alkaline phosphatase enzyme
      activity, which was not altered by treatment with CGRP or either PTH(1-34) or
      1,25(OH)2D3. Stimulation with 2.5 x 10(-8)M 1,25(OH)2D3 did produce a 7.6-fold
      increase in osteocalcin. These results indicate that pulp cells possess the
      cellular machinery to respond to CGRP and that stimulation of the production of
      BMP-2, a factor known to be associated with induction of dentin formation, is a
      component of the response.

PMID- 9587317
TI  - Evaluation of the biocompatibility of a nonceramic hydroxyapatite.
AB  - In this study, the biocompatibility of calcium phosphate cement (CPC) was
      systematically investigated, which included systemic injection acute toxicity
      assay, cell culture cytotoxicity assay, gene mutation assay (Ames test),
      chromosome aberration assay (micronucleus test), DNA damage assay (unscheduled
      DNA synthesis test) and implant histological evaluation. The results showed that
      the CPC had no toxicity and all tests for mutagenicity and potential
      carcinogenicity of CPC extracts are negative. CPC was implanted into the femurs
      of rabbits under no-load condition and the histology of specimens revealed that
      the implant tightly joined with the surrounding bone, only a very slight
      histological inflammatory reaction occurred. Thus, CPC is a highly biocompatible
      material and seems to be safe for application in humans.

PMID- 9587318
TI  - The effect of endodontic materials on periodontal ligament cell proliferation,
      alkaline phosphatase activity, and extracellular matrix protein synthesis in
      vitro.
AB  - Recent studies have demonstrated that periodontal ligament-derived (PDL) cells
      have the potential to regenerate a complete periodontal connective tissue
      attachment apparatus on both root and artificial substrates. To study the
      characteristics of endodontic materials conducive to periodontal regeneration, we
      have established an experimental model using PDL cell cultures that express a 42
      kDa protein (CP42) associated with cementum extracellular matrix. In this report,
      the effect of gutta percha, dental amalgam, composite and calcium hydroxide on
      PDL cell proliferation, collagen and noncollagen protein synthesis, alkaline
      phosphatase activity, and CP42 expression are presented. While all substrates
      supported PDL cell attachment and proliferation, highest levels of alkaline
      phosphatase activity, collagen and noncollagen protein synthesis were observed in
      control cultures. Lowest levels of the above parameters were observed with gutta
      percha while amalgam, composite and calcium hydroxide had intermediate levels.
      Only control PDL cultures demonstrated CP42 expression. These data suggest that
      culture substrate can markedly influence periodontal extracellular matrix gene
      expression in vitro and provide an experimental model to select and develop
      endodontic materials compatible with periodontal regeneration in vivo.

PMID- 9587319
TI  - Histological evaluation of the effectiveness of five instrumentation techniques
      for cleaning the apical third of root canals.
AB  - The efficacy of five instrumentation techniques for cleaning the apical third of
      curved root canals was assessed by histological examination. Mesial root canals
      of freshly extracted human mandibular molars were prepared by the following
      instrumentation methods: step-back technique using stainless steel files; step
      back technique using nickel-titanium files; ultrasonic technique; balanced force
      technique; and Canal Master U technique and instruments. The apical portion of
      the root was histologically processed, and cross-sections were examined for
      remaining soft tissue, predentin, and debris. The results showed no significant
      differences among the techniques. Although the five instrumentation methods were
      effective in removal of major amounts of tissue from the canals, none totally
      debrided the entire root canal system, especially when variations in the internal
      anatomy were present.

PMID- 9587320
TI  - A comparison of canal centering ability of four instrumentation techniques.
AB  - The purpose of this study was to compare three engine driven (nickel-titanium)
      NiTi instrument systems with hand files for their effect on canal transportation.
      Mesial roots of mature lower first molars with separate canals were paired on the
      basis of curvature and morphology. Canal lengths were standardized to 11 mm from
      orifice to apical foramen. Profile, Lightspeed, McXIM, and Flex-R hand filing
      techniques respectively were randomly assigned to one of the four canals of each
      tooth pair. The roots were mounted and sectioned at 1 mm, 3 mm, and 5 mm from
      working length using a modified Bramante technique. All sections were video
      imaged preoperatively after instrumentation to size #30 and after final
      instrumentation to size #40. The images were computer analyzed for changes in
      canal area and centering at each stage of instrumentation. Preparation time was
      also recorded. Data were analyzed using ANOVA. The NiTi systems remained better
      centered in the canal than stainless steel hand files. There were no significant
      differences among the NiTi systems at any level. The difference between hand
      filing and the NiTi techniques was more pronounced at size #40 than at size #30.
      The NiTi systems were all significantly faster than hand filing. No significant
      differences in preparation were found between the NiTi systems when canals were
      instrumented to the size nearest #40.

PMID- 9587321
TI  - Coronal leakage: effects of smear layer, obturation technique, and sealer.
AB  - Coronal microleakage may be a major factor in the etiology of treatment failure.
      This study examined the effect of obturation technique, sealer, and the presence
      of smear layer on coronal microleakage. Two hundred extracted human teeth were
      assigned to 20 treatment groups. Groups were examined with the smear layer
      present or smear layer removed (17% REDTA). Access cavities were exposed to
      artificial saliva then Pelikan Ink. Teeth were cleared and linear dye penetration
      measured. When all groups with the smear layer removed were compared with all
      groups with the smear layer present, significantly less leakage was seen when the
      smear layer was removed. Ultrafil displayed significantly more leakage than all
      other groups. Vertical compaction of lateral condensation and Thermafil
      obturations significantly reduced leakage. AH-26 displayed significantly less
      leakage than Roth's 811 sealer. These results indicate that removal of the smear
      layer, the use of AH-26, and vertical compactin have cumulative effects in
      reducing coronal leakage.

PMID- 9587322
TI  - Detection of IgA subclasses and J chain mRNA bearing plasma cells in human dental
      periapical lesions by in situ hybridization.
AB  - Humoral immune responses are implicated in the pathogenesis of human dental
      periapical lesions. To elucidate whether IgA-associated immune systems play a
      role in the lesions, the in situ hybridization technique was used to detect J
      chain mRNA expression, which is correlated with the secretion of dimeric IgA. In
      addition, IgA subclass mRNA-expressing cells were also investigated by double
      target in situ hybridization (ISH) methodology using digoxigenin- and biotin
      labeled IgA subclass specific oligonucleotide probes. This double target ISH
      technique involved immunochemical detection with an alkaline phosphatase
      conjugated antibody and a peroxidase conjugated avidin-biotin complex system to
      detect IgA subclass mRNA in the formalin-fixed, paraffin wax embedded periapical
      tissue sections. Twenty-four biopsy samples (16 periapical granulomas and 8
      radicular cysts) were examined. IgA subclass mRNA positive plasma cells were
      detected in all samples. IgA1 mRNA-expressing cells were predominant both in
      granulomas and cysts (mean = 75.3 +/- 11.2%, 64.8 +/- 21.3%, respectively), and
      the IgA1 proportion was higher in granulomas than in cysts, although no
      significant difference was seen between the two lesions (p = 0.132). J chain mRNA
      positive cells were very sparsely detected in 21/24 cases. The median percentages
      of J chain mRNA positive cells/IgA mRNA positive plasma cells (4.7%, range 0.3
      13.6%) in cysts were significantly higher than in granulomas (1.3%, range 0-7.7%;
      p = 0.03). This result supports the hypothesis that dimeric IgA may be more
      actively produced in radicular cysts than in granulomas. These features are
      thought to reflect the local activation of the periapical immune system in
      response to environmental factors and indicate that secretory IgA mediated immune
      defense systems appear to play little role in these lesions. Our results indicate
      that the IgA-associated immune response in periapical lesions is more similar to
      serum or systemic IgA responses than to mucosa-associated immune responses where
      dimeric IgA predominates.

PMID- 9587323
TI  - Fibroblast growth in vitro suppressed by LPS-activated macrophages. Reversal of
      suppression by hydrocortisone.
AB  - Activated macrophages are among the major constituents of the periapical
      granuloma. Their state of activation may persist for long periods after the local
      irritant is removed and may delay resolution and repair of the lesion. The effect
      of activated macrophages on fibroblast growth was studied in vitro. Circular
      fibroblast colonies were formed using a drop containing 7.5 x 10(5) murine dermal
      fibroblasts and allowed to grow for 7 days. When peritoneal exudate macrophages
      were added (0.5-3.0 x 10(6) cells/dish) and activated in vitro by LPS (1
      microgram/ml), the fibroblast colony's growth was suppressed. LPS alone, at the
      concentration used, had no effect on the fibroblast growth. Hydrocortisone (> or
      = 10(-7) M) totally reversed the suppression, when added either simultaneously
      with or 6, 24, or 48 h after the LPS. The efficacy of late hydrocortisone
      treatment suggests that its effect was through prevention of the expression of
      the LPS activation of the macrophages. These findings may provide a possible clue
      to a pharmacological modulation of the healing processes that occur in the
      periapical lesion once its infective source had been eliminated.

PMID- 9587324
TI  - Determination of the p-monochlorophenol residue in the calcium hydroxide + P
      monochlorophenol combination used as an intracanal dressing in pulpless teeth of
      dogs with induced chronic periapical lesion.
AB  - To determine the presence of p-monochlorophenol in the calcium hydroxide (Calen)
      + p-monochlorophenol combination after its use as intracanal dressing, periapical
      lesions were induced in 60 root canals of upper and lower premolars of four dogs.
      After biomechanical preparation, the root canals received the intracanal
      medication, which was removed from the apical third after 2, 4, 7, and 14 days
      for chemical analysis by spectrophotometry. The results showed a p
      monochlorophenol loss of approximately 50.0% in the dressing after 48 h, with no
      further significant loss after longer periods of times. p-Monochlorophenol was
      still present in the medication after 14 days.

PMID- 9587325
TI  - Evaluation of a combined surgical repair and guided tissue regeneration technique
      to treat recent root canal perforations.
AB  - This study evaluated a technique that included retrofill to repair molar root
      canal perforations and guided tissue regeneration to restore the periodontium
      that was removed from the furcation area for access to the sites. Six dogs had
      root canal therapy on mandibular fourth premolars and first molars. The distal
      root of each tooth was perforated on the furcation aspect halfway between the
      furcation and the apex. Replaced flap surgery was performed for access to prepare
      and fill the perforation site with intermediate Restorative Material. A bone
      xenograft was placed in the access ostectomy site and covered with GoreTex
      Augmentation Material (GTAM). Controls included unfilled perforations and not
      using bone grafts and/or GTAM. Dogs were killed at 6, 12, and 24 wk postsurgery.
      Complications were more common when root perforations were left unfilled.
      Histomorphometry revealed a statistically significant decrease in inflammation
      and more bone fill when root perforations were filled and GTAM was used,
      respectively.

PMID- 9587326
TI  - The relationship of root canal enlargement to finger-spreader induced vertical
      root fracture.
AB  - The purpose of this study was to assess the effect of lateral condensation forces
      on the development of vertical root fracture (VRF) in teeth that have undergone
      controlled, measured internal root reduction (i.e. canal preparation). Thirty
      four straight-rooted maxillary anterior teeth were used. For each tooth a
      simulated PDL was fabricated from a uniform 0.15 mm layer of silicone impression
      material. The teeth were mounted in resin to facilitate removal for observation.
      They were radiographed and measured at 2, 4, 6, and 8 mm from the apex. They were
      prepared with the step-back method so that the canal width was 20% of the total
      root width at 2, 4, 6, and 8 mm from the apex. They were obturated using a fine
      finger spreader attached to a jig that produced a static force of 3.3 kg for 15 s
      after placement of each gp point. Obturation was complete when the spreader did
      not penetrate apical to 8 mm from the apex. Twenty-four h after obturation the
      teeth were examined by transillumination for VRF. Teeth not exhibiting VRF were
      tested further after gp removal and canal enlargement of 30%, 40%, and 50% The
      teeth were sectioned at 2-mm increments with a diamond wafering saw and examined
      under stereomicroscope. No VRF occurred at 20% or 30%; 5 teeth fractured at 40%
      and 7 at 50%. These teeth had root surface craze lines that developed during
      testing. Craze lines had also developed in all 17 of the remaining unfractured
      samples. No VRF occurred after testing unless craze lines were previously
      present.

PMID- 9587327
TI  - Effect of root canal contents on healing of teeth with dentin-bonded resin
      composite retrograde seal.
AB  - Healing results were compared among 551 infected roots apically sealed with a
      dentin-bonded resin composite (Gluma-Retroplast). These roots contained either 1)
      root filling to apex after resection, 2) insufficient root filling, or 3) empty
      root canals with necrotic pulp remnants. At 2- to 4-yr follow-up, complete bone
      healing was found to be 92%, 85%, and 81% in groups 1, 2, and 3, respectively.
      The results from groups 1 and 3 were significantly different, and the results
      from group 2 did not differ significantly from that of groups 1 or 3. Reasons for
      "Failures" were found to be mainly loose filling or uncovered canal. After 21
      roots classified as "Failures" were reoperated, 76% of these showed "Complete
      Healing" after 1 yr.

PMID- 9587328
TI  - Dental erosion associated with the use of imported, low-pH snacks.

PMID- 9587329
TI  - Vascular surgery--quo vadis?

PMID- 9587330
TI  - Cystic adventitial disease of the popliteal artery: diagnosis and treatment.
AB  - PURPOSE: This paper represents the presentation of a case of cystic adventitial
      disease of the popliteal artery and an exhaustive review of the literature with
      an emphasis on optimal means for diagnosis and treatment of this unusual disease.
      METHODS: We collect all reported cases of cystic adventitial disease of the
      popliteal artery since the last review in 1987 with an additional review of these
      cases reported in the U.S. since the initial description of the disease. RESULTS:
      We found 264 cases of cystic adventitial disease (CAD) of the popliteal artery
      from 1954 to 1995, with 38 reported in the U.S. Fifty-eight new cases of CAD have
      been reported since the last review in 1987; 11 of these were reported in the
      U.S. Diagnosis of the disease has improved in the last few years with non
      invasive techniques. Duplex color scanning followed by T2-weighted MRI now
      appears to be the best diagnostic choice. Various therapeutic methods have been
      described for the treatment of CAD. The recommended treatments are excision of
      the cyst with the cystic wall when the artery is stenotic and resection of the
      affected artery, followed by an interposition graft, when the artery is occluded.
      CONCLUSION: Claudication in young, healthy patients resulting from popliteal
      artery stenosis or occlusion is a leading symptom of CAD. This disease affects
      males in a ratio of approximately 5:1 and appears predominantly in the fourth and
      fifth decades. The incidence is approximately 1 in 1200 cases of claudication or
      1 in 1000 peripheral arteriograms. The predominance of reported cases is found in
      Japan and Europe. Optimal diagnostic techniques include duplex color scanning and
      T2-weighted MRI. The lesions can be effectively treated by resectional or non
      resectional means depending on the presence or absence of complete arterial
      occlusion.

PMID- 9587331
TI  - Cognitive testing in patients undergoing carotid endarterectomy.
AB  - OBJECTIVES: To determine by literature review the effect of carotid
      endarterectomy (CEA) as a modulator of cognitive function in patients with
      carotid arterial disease. Derive recommendations for standardising cognitive
      testing of patients with carotid arterial disease. DESIGN AND METHODS: The
      English language literature was interrogated using a CD-ROM driven medline search
      using carotid endarterectomy and cognitive function as keywords between 1986
      1995. These subsets were scanned and papers of direct relevance or commonality
      were selected. Cited papers prior to 1986 from these references were then sought
      directly. RESULTS: There are few controlled studies reporting on the effect of
      CEA. There is no consensus in the literature for the effect of CEA on cognition
      or which tests should be used. Studies reporting a benefit for CEA lack a control
      group and fail to eliminate the effect of practice. Reports suggesting cognitive
      impairment following CEA performed follow-up tests early. CONCLUSIONS: There are
      many methodological problems with the study of cognitive function before and
      after carotid endarterectomy and wide disagreement in the interpretation of
      results. Further studies should contain control groups, use tests resistant to
      practice and be performed when the effects of surgery and anaesthesia are passed.

PMID- 9587332
TI  - Early and long-term results in the surgical treatment of juxtarenal and pararenal
      aortic aneurysms.
AB  - OBJECTIVE: Surgical treatment of juxtarenal and pararenal aortic aneurysms (JPAA)
      provide technical problems which may influence short- and long-term results;
      however few surgical series have been published on this subject. The purpose of
      this study is to observe predictors of results in a series of JPAA and to analyse
      long-term survival of these patients. DESIGN, MATERIALS AND METHODS: Patients'
      epidemiology and surgical technique used in all cases of JPAA were reviewed and
      correlated with early results through logistic regression analysis. Early results
      were compared with those of infrarenal aneurysms (IAA) treated in the same
      period. Long-term results were obtained through our surveillance protocol (3
      months after surgery and yearly thereafter) and calculated by life-table
      analysis. RESULTS: Fifty JPAA were identified over a total of 1450 aortic
      aneurysms (3.4%). Surgical approach was: anterior transperitoneal in 38 cases
      (96%), extended retroperitoneal in one (2%) and thoracoabdominal in one (2%).
      Suprarenal control was obtained in all cases; at the diaphragm in seven (14%),
      above both renal arteries in 17 (34%) and above one renal artery in 16 cases
      (32%). Renal revascularisation was performed in 11 cases (22%; nine unilateral
      and two bilateral). Overall perioperative mortality was 12%, significantly
      greater than mortality of IAAs: 50/1400, 3.5% (p < 0.02). Mortality in elective
      cases was 3/42, 7.1% and in ruptured JPAA 3/8, 37.5%. Independent predictors of
      early mortality were aneurysm rupture, age > 70 years, and coronary artery
      disease. Gender, smoking, hypertension, diabetes mellitus, site of proximal
      aortic clamping, type of aortic reconstruction, visceral revascularisation, and
      technically difficult cases were not associated with early mortality. Three and
      five year survivals were 66.8% +/- 9.93 and 40.0% +/- 12.64, respectively.
      CONCLUSIONS: Surgical treatment of JPAAs is associated with a higher risk of
      early mortality compared to IAAs and reduced long-term survival. Indications for
      surgery in JPAAs should consider the risk/benefit ratio rather than focusing on
      technical aspects which do not seem to significantly influence results.

PMID- 9587333
TI  - Magnetic resonance imaging and MR angiography of endoluminally treated abdominal
      aortic aneurysms.
AB  - OBJECTIVES: To evaluate magnetic resonance imaging (MRI) with gadolinium-based
      contrast medium-enhanced MR angiography (MRA) for the follow-up of endoluminally
      treated abdominal aortic aneurysms. DESIGN: MRI/MRA, angiography and computed
      tomography (CT) were performed 1 month after endoluminal stent-graft placement.
      MRI/MRA was repeated at 6 and 12 months and angiography and CT were added to
      confirm unexpected findings. MATERIALS: Fifteen male patients with endoluminally
      treated abdominal aortic aneurysms. METHODS: MRI with MRA, spiral CT with
      transverse images and angiography were performed. RESULTS: MRI/MRA demonstrated
      changes of stent-graft morphology, aortic neck- and aneurysmal diameter, stent
      graft blood flow, stent-graft leakage, blood flow in lumbar arteries, intra
      aneurysmal thrombus, periaortic inflammation and vertebral body infarction. For
      most of these features MRI/MRA provided more information than angiography and/or
      CT. MRI was the only method demonstrating thrombus reorganisation and vertebral
      body infarction. CONCLUSIONS: MRI with MRA provides the relevant information
      needed for follow-up of endoluminally treated abdominal aortic aneurysms (AAA).
      This may be the method of choice because of its use of contrast media with very
      low nephrotoxicity, lack of ionising radiation and non-invasiveness.

PMID- 9587334
TI  - Prediction of the immediate outcome of femoropopliteal saphenous vein bypass by
      angiographic runoff score.
AB  - OBJECTIVES: To determine the value of the Ad Hoc scoring system (SVS/ISCVS) in
      predicting the immediate outcome of femoropopliteal saphenous vein grafts.
      DESIGN: Retrospective study. MATERIALS: One hundred and twenty patients underwent
      132 primary femoropopliteal vein bypass procedures, 32 for claudication and 100
      for critical leg ischemia (CLI). METHODS: The outflow arteries were graded
      according to the Ad Hoc scoring system (SVS/ISCVS). Postoperative immediate graft
      patency and leg salvage to the period of the first 30 days after surgery.
      RESULTS: Ninety-one per cent of claudicants and 83% of CLI patients had immediate
      patency. The overall 30-day patency rate was 85%. Leg salvage rate was 91% for
      the patients with CLI. Patients with score in the highest quartile were found to
      have a 8.7 times higher risk for immediate graft occlusion (p = 0.005).
      Multivariate analysis showed that the Ad Hoc score was predictive of immediate
      patency (p = 0.0006) and leg salvage (p = 0.0004). In patients with a score < or
      = 7.5 and in those with a score > 7.5, the patency rates were 95% and 66% (p =
      0.001), and the leg salvage rates were 97% and 80%, (p = 0.004), respectively.
      CONCLUSIONS: The Ad Hoc scoring system is useful in predicting the immediate
      outcome of femoropopliteal saphenous vein grafts.

PMID- 9587335
TI  - Vascular endothelial growth factor (VEGF) expression during arterial repair in
      the pig.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) is reported to be a potent
      and specific mitogen for endothelial cells (EC) and an inducer of angiogenesis in
      vivo. Originally called vascular permeability factor (VPF), VEGF also increases
      permeability of microvessels to circulating macromolecules. The aim of this study
      was to examine whether the VEGF gene was expressed in porcine arteries following
      denudation of EC. DESIGN: Experimental animal model with mechanical injury to
      large arteries. METHODS: The right iliac artery of juvenile pigs was de
      endothelialised using an inflated balloon catheter. At a number of time-points
      after injury, these arteries were harvested together with uninjured contralateral
      arteries. Sections of arteries were used for RNA analysis by Northern blots and
      for protein localisation studies by immunohistochemistry. RESULTS: Two VEGF
      transcripts (2.0 kb, 4.5 kb) were markedly elevated in pig arteries soon after
      injury. Newly synthesised VEGF protein was located in smooth muscle cells (SMC)
      throughout the media of injured arteries. CONCLUSIONS: The elevated expression of
      VEGF by SMC in denuded porcine arteries is evidence that this cytokine plays a
      role in the injury response of large arteries. Since several biological
      activities have been identified for VEGF, the function of this cytokine in the
      arterial repair process remains to be determined.

PMID- 9587337
TI  - Plasma D-dimer measurement in patients with suspected DVT--a means of avoiding
      unnecessary venography.
AB  - OBJECTIVES: To assess the applicability of plasma D-dimer levels in the exclusion
      of a DVT. DESIGN: Consecutive cohort of patients. MATERIALS AND METHODS: Eighty
      consecutive patients presenting to the radiology department with a clinical
      diagnosis of DVT were included. Citrated blood samples were taken from all
      patients before radiological investigation, plasma isolated and frozen for
      subsequent testing. The patients then underwent venography (duplex scan was also
      used in some cases). Plasma samples were tested using the NycoCard D-Dimer.
      NycoCard Reader was used to estimate the D-dimer concentrations. RESULTS: A DVT
      was diagnosed in 29 cases (36.7%). Plasma D-dimer levels had a sensitivity of 96%
      (only one false negative), specificity of 40%, positive predictive value of 48%,
      and negative predictive value of 95% when compared to venography. CONCLUSIONS: A
      normal plasma D-dimer level could be used as an exclusion test for DVT avoiding
      complications of venography and saving time and money.

PMID- 9587336
TI  - Bilateral infrainguinal vein grafts and the incidence of vein graft stenosis.
AB  - OBJECTIVES: To elucidate the incidence of significant vein graft stenosis in
      patients who have undergone bilateral infrainguinal vein grafts. MATERIALS:
      Between 1987 and 1996, 22 patients were identified from our vascular studies
      database as having undergone bilateral infrainguinal vein bypass grafting.
      METHODS: Data was obtained from the vascular studies database and by case note
      review. All patients had been part of a vein graft surveillance programme.
      RESULTS: Of the 22 patients with bilateral vein grafts, eight were excluded from
      further analysis because one or more of their grafts failed within 30
      postoperative days. In the remaining 14 patients (28 vein grafts) there were 15
      primary vein graft stenoses. Six patients (43%) had bilateral vein graft
      stenoses, which is significantly higher (p = 0.0008) than the predicted value of
      9%, for developing bilateral vein graft stenoses. For those patients who
      developed a vein graft stenosis in their first grafted limb (9/14), 67% (6/14)
      subsequently developed a vein graft stenosis in their second grafted limb.
      CONCLUSION: Patients who develop vein graft stenosis in one limb are at a greater
      risk of developing a contralateral vein graft stenosis if that limb is grafted.
      This may well be due to individual vein morphology or unidentified systemic
      factors that play a role in the aetiology of vein graft stenosis.

PMID- 9587339
TI  - The effects of potassium channel openers on saphenous vein exposed to arterial
      flow.
AB  - OBJECTIVES: To assess the sensitivity of saphenous vein to potassium channel
      opening drugs (KCOs). METHODS: Saphenous vein, harvested at bypass surgery or
      high ligation for correction of varicose veins, was exposed to an in vitro flow
      circuit and vasomotor responses assessed by organ bath pharmacology. OUTCOME
      MEASURES: Effective drug concentrations for 50% reduction in vein ring tension
      (IC50). RESULTS: Vein rings pre-contracted with phenylephrine showed a
      concentration-dependent relaxation to all the KCOs tested with a potency ranking
      of HOE 234 > cromakalim > pinacidil > diazoxide. The relaxation to cromakalim was
      endothelium-independent and was inhibited by glibenclamide (an ATP-sensitive K+
      channel blocker). The sensitivity of vein rings to cromakalim increased after
      exposure to arterial flow conditions for 90 minutes (IC50 before 1.7 +/- 0.25
      microM and after 0.25 +/- 0.08 microM, p > 0.001). This effect was not evident
      after 90 min of venous flow conditions, 2.19 +/- 0.49 microM. When the workload
      on vein, exposed to arterial flow conditions, was reduced mechanically by
      external stenting with PTFE the increased sensitivity to cromakalim was
      abolished. CONCLUSIONS: Saphenous vein has ATP-sensitive K+ channels responsive
      to KCOs. The increased sensitivity to cromakalim, induced by arterial flow
      conditions, may represent an endogenous protective mechanism limiting ischaemic
      damage resulting from the higher workload imposed on grafted vein.

PMID- 9587338
TI  - Sympathetic skin response and patient satisfaction on long-term follow-up after
      thoracoscopic sympathectomy for hyperhidrosis.
AB  - OBJECTIVES: To determine effect of sympathectomy for hyperhidrosis on sympathetic
      skin response (SSR) during long-term follow-up. Patient satisfaction was assessed
      and surgical complications noted. DESIGN: Prospective, Open, Non-randomised
      study. MATERIALS AND METHODS: Patients who had undergone bilateral thoracoscopic
      sympathectomy for hyperhidrosis underwent postoperative assessment of SSRs. A 15
      mA stimulus was applied over the median nerve contralateral to the sympathectomy
      and evoked electrodermal activity was recorded from the sympathectomised palm
      using a Dantec Counterpoint Mk 2. Patient satisfaction with surgery was assessed
      by questionnaire and visual analogue score (0-1.0). RESULTS: Of 26 patients, 21
      were female. Mean (range) age was 23 (9-36) years. Mean (range) follow up was 39
      (4-138) months. 12% of cases had residual or recurrent symptoms. Median (range)
      patient satisfaction was 0.83 (0.06-1.0). In 7/52 palms recurrent SSRs were not
      detected. Repeated measures analysis of variance found amplitude of SSR to be of
      low significance with respect to time since surgery (F = 0.48; p = 0.49) and
      incidence of compensatory sweating (F = 2.38; p = 0.14). CONCLUSION:
      Thoracoscopic sympathectomy for hyperhidrosis is an effective procedure.
      Following sympathectomy SSRs are not permanently abolished, but return of SSRs
      does not correspond with symptom recurrence. As such, SSRs are a poor tool for
      objective assessment of long-term outcome following sympathectomy.

PMID- 9587340
TI  - Variation in management of intermittent claudication by vascular surgeons in
      Scotland. Scottish Vascular Audit Group [corrected].
AB  - OBJECTIVES: The principal aim was to determine the extent to which intended and
      actual management varied among vascular surgeons. DESIGN: Prospective survey.
      METHODS: A nationwide survey of initial management of, and determination of
      subsequent surgical management in, 1180 patients with a diagnosis of intermittent
      claudication made by 28 vascular surgeons was carried out in Scotland. RESULTS:
      The proportion of patients considered for conservative management varied between
      consultants from 10-83% (mean 42%, S.D. 16%). The proportion considered for
      angiography varied from 13-80% (mean 46%, S.D. 14%). For surgery, the range was 4
      68% (mean 37%, S.D. 14%) and for angioplasty the range was 13-90% (mean 49%, S.D.
      19%). All differences in management intention between consultants were
      significant (p < 0.001). The differences between consultants in terms of
      treatment actually received within 6 months were less striking but still
      significant (p < 0.05). All consultants actually managed more patients
      conservatively than they had originally intended, but there was poor correlation
      between intended and actual practice. CONCLUSIONS: In Scotland the variations
      between surgeons in both intended and actual management are substantial. Large
      scale randomised controlled trials of treatment of claudication are urgently
      required to make clear the best treatment strategies.

PMID- 9587341
TI  - Common iliac artery aneurysms in patients with abdominal aortic aneurysms.
AB  - OBJECTIVES: To determine the incidence of common iliac artery (CIA) aneurysms in
      patients with abdominal aortic aneurysms (AAA) and to evaluate the relationship
      between AAA and CIA diameter. METHODS: Spiral CT angiography was used to measure
      the maximum diameters of the abdominal aorta and the common iliac arteries of 215
      patients with AAA. RESULTS: The median CIA diameter was 1.7 cm--significantly
      greater than the published mean of 1.25 (2 S.D. = 0.85-1.65) cm of an age
      matched, non-vascular population. Thirty-four patients (16%) had unilateral and
      26 patients (12%) bilateral CIA aneurysms > or = 2.4 cm diameter. Eight-six
      vessels (20%) were affected. Right CIA diameters were wider than left CIA
      diameters (p < 0.0001, Wilcoxon matched-pairs signed rank test). The correlation
      between AAA size and CIA diameter was weak. CONCLUSIONS: The AAA population has
      abnormally dilated common iliac arteries. In this population, common iliac artery
      aneurysms should be defined as those greater than 2.4 cm diameter. 20% of CIAs in
      patients with AAA are aneurysmal according to this definition.

PMID- 9587343
TI  - Full-dose and half-dose Klean Prep produce clearer images with iliac duplex
      examination than picolax.
AB  - OBJECTIVES: Iso-osmotic bowel preparation (Klean Prep) improves the accuracy of
      iliac duplex examination and reduces the time of each examination. Full-dose
      Klean Prep entails 4 l of fluid. We studied the effect of 2 l of Klean Prep (half
      dose) and Picolax on image quality. DESIGN: Prospective study comparing clarity
      of duplex examination after three different bowel preparation regimes with that
      after 12 h starvation. MATERIALS AND METHODS: Thirty patients underwent iliac
      duplex examination after 12 h starvation. Scans were scored subjectively for grey
      scale and colour image quality, and Doppler signal-to-noise ratio. Patients were
      allocated blindly to: (a) full-dose Klean Prep, (b) half-dose Klean Prep, or (c)
      Picolax. After out-patient preparation, the scan was repeated and scored by the
      same observer, blinded to the preparation. RESULTS: Both full- and half-dose
      Klean Prep produced significant improvements in image quality for all three
      modalities; Picolax produced minimal change. There was minimal advantage of full
      dose over half-dose Klean Prep. Patients preferred half-dose Klean Prep to full
      dose. CONCLUSION: Klean Prep significantly improves the image obtained by iliac
      duplex examination; Picolax does not. Half-dose Klean Prep is an acceptable
      preparation to patients.

PMID- 9587342
TI  - At what peak velocity ratio value should duplex-detected infrainguinal vein graft
      stenoses be revised?
AB  - OBJECTIVES: To determine the peak velocity ratio (PVR) threshold at which to
      intervene and correct duplex detected vein graft stenoses. DESIGN: Prospective
      study. MATERIALS: Infrainguinal vein grafts in patients attending the vascular
      studies for routine postoperative surveillance. METHODS: Colour duplex detected
      stenotic vein graft lesions with a peak velocity ratio (PVR) between 2.0 and 2.9
      were identified and monitored by serial duplex scans performed monthly for 3
      months and then at 3-monthly intervals thereafter. At the end of the study
      period, the outcome of these lesions were analysed. RESULTS: Thirty-eight lesions
      were identified from 32 grafts. Of these lesions, sixteen (42%) resolved, 11
      (29%) remained stable and 11 (29%) progressed to a PVR of > or = 3.0 and
      underwent angioplasty. There were no occlusions in any of the grafts during the
      period of study. CONCLUSIONS: Colour duplex detected vein graft stenoses with a
      PVR of less than 3.0 can be treated expectantly if grafts with stenoses with a
      PVR 2.0-2.9 are scanned every month for at least 3 months after detection.

PMID- 9587344
TI  - The value of QTc dispersion in assessment of cardiac risk in elective aortic
      aneurysm surgery.
AB  - OBJECTIVES: To determine the value of QTc dispersion in predicting cardiac risk
      in aortic aneurysm surgery. DESIGN: Retrospective case-control study. MATERIALS:
      One hundred and twenty-six patients who had abdominal aortic aneurysm surgery
      between May 1992 and April 1996. METHODS: Nine patients experienced a
      postoperative cardiac complication defined as myocardial infarction or cardiac
      death. Twenty-four age and sex-matched controls who had uncomplicated aortic
      surgery were selected at random. QTc dispersion was calculated from the
      preoperative 12 lead electrocardiograms. RESULTS: The mean QTc dispersion in the
      cardiac complication group was greater than the control group (63.1 ms1/2 vs.
      50.4 ms1/2) but the difference did not approach statistical significance.
      CONCLUSIONS: QTc dispersion cannot be recommended as a predictor of cardiac
      complication following elective aneurysm repair.

PMID- 9587345
TI  - Double primary aortoenteric fistula.

PMID- 9587346
TI  - Ruptured popliteal aneurysm infected with Salmonella enteritidis: an unusual
      cause of leg swelling.

PMID- 9587347
TI  - CD14-dependent activation of human endothelial cells by Bacteroides fragilis
      outer membrane.
AB  - We studied the capacity of isolated Bacteriodes fragilis outer membrane, B.
      fragilis NCTC9343 lipopolysaccharide (LPS; endotoxin), and B. fragilis NCTC9343
      capsular polysaccharides to activate human umbilical vein endothelial cell
      (HUVEC) monolayers. To assess HUVEC activation, E-selectin expression was
      measured by enzyme-linked immunosorbent assay (ELISA), Northern blot analysis for
      E-selectin-specific mRNA, and electrophoretic gel mobility shift assay (EMSA) for
      NF-kappa B, a transcription factor necessary for E-selectin gene activation.
      Exposure of HUVECs to B. fragilis outer membrane fractions, separated from other
      components of the B. fragilis cell wall by isopycnic, sucrose gradient
      centrifugation, significantly increased surface expression of E-selectin and
      induced functional endothelial cell-dependent leukocyte adhesion. B. fragilis
      outer membranes induced translocation of NF-kappa B to HUVEC nuclei and
      accumulation of E-selectin mRNA in HUVEC cytoplasm. E-selectin expression induced
      by B. fragilis outer membranes was not blocked by polymixin B. In contrast, E
      selectin expression induced by outer membrane fractions purified from E. coli was
      competitively inhibited by polymixin B. Neither purified B. fragilis LPS, a
      prominent constituent of the outer membrane, nor purified B. fragilis capsular
      polysaccharides induced HUVEC activation. Two different monoclonal antibodies
      directed against human CD14 completely inhibited B. fragilis outer membrane
      induced NF-kappa B activation, E-selectin transcription, and E-selectin surface
      expression. We conclude that the outer membrane component of the B. fragilis cell
      wall contains a proinflammatory factor(s), that is not LPS, which induces human
      endothelial cell activation by a soluble CD14-dependent mechanism.

PMID- 9587348
TI  - A model to investigate postoperative ileus with strain gauge transducers in awake
      rats.
AB  - BACKGROUND: Postoperative ileus influences patients well-being, hospital stay,
      and health cost, and postoperative inhibition of colonic motility is a major
      contributor to postoperative ileus. Experimental models for investigating
      postoperative ileus are needed. In particular, recording of postoperative colonic
      motility in awake rats has not been described yet. MATERIAL AND METHODS: Gastric,
      small intestinal, and colonic motility were recorded with strain gauge
      transducers in awake rats, and the effects of anesthesia and abdominal surgery on
      gastrointestinal motility were investigated. RESULTS: Ether anesthesia increased
      gastric motility and inhibited small intestinal motility, while enflurane
      anesthesia had only minor effects on gastrointestinal motility. Abdominal surgery
      inhibited gastric, small intestinal, and colonic motility, and a detailed
      analysis of gastrointestinal motility in our postoperative ileus model is given.
      CONCLUSIONS: We established a model to record gastric, small intestinal, and
      colonic motility in awake rats postoperatively. We could demonstrate that
      enflurane anesthesia had little effect on gastrointestinal motility, while
      laparotomy and short manipulation of the cecum produced a prolonged inhibition of
      gastrointestinal motility. Our model could be used to investigate postoperative
      ileus, particularly of the colon, in awake rats.

PMID- 9587349
TI  - Nitric oxide donor decreases neutrophil adhesion in both lung and peritoneum
      during peritonitis.
AB  - BACKGROUND: As nitric oxide (NO) is an antiadhesive molecule, exogenous NO may
      modulate neutrophil adhesion in organs. This study was designed to examine the
      effects of the NO donor SNAP (S-nitroso-acetyl penicillamine) on neutrophil
      adhesion at the inflammatory site and in remote organs, in peritonitis using a
      fluorescent microscopic method. MATERIALS AND METHODS: In experiment 1, rats (n =
      12) were given saline or 10 micrograms/kg of SNAP intravenously followed by
      continuous infusion of saline, or of 2, 20, or 200 micrograms/kg/h SNAP until
      sacrifice. Ten minutes after injection of saline or SNAP, 10(7) Escherichia coli
      were injected into the peritoneal cavity. Five hours after challenge, 10(6)
      fluorescein-labeled neutrophils were infused. Peritoneal samples, lungs, liver,
      and kidney were harvested for counting of labeled neutrophils under
      epifluorescent microscopy. In experiment 2, rats (n = 25) were treated with
      saline or 10 micrograms/kg of SNAP intravenously and infused with saline or 20
      micrograms/kg/h SNAP; E. coli was injected as in experiment 1. Before or 5 h
      after challenge, hemodynamic data were obtained. Then, labeled neutrophils were
      infused for counting of neutrophil numbers in organs. Arterial blood gas data and
      the circulating neutrophil number were also determined. RESULTS: Experiment 1.
      Twenty and 200 micrograms/kg/h SNAP infusions tended to reduce labeled neutrophil
      numbers in lungs, while all three SNAP doses decreased the peritoneal labeled
      neutrophil numbers. RESULTS: Experiment 2. Five hours after bacterial injection,
      SNAP infusion simultaneously decreased both pulmonary and peritoneal labeled
      neutrophil numbers. SNAP had no effect on hemodynamic and blood gas data, or on
      circulating neutrophil numbers. CONCLUSION: NO donors may be useful for
      preventing neutrophil-associated lung injury, but should be used with caution in
      light of the possible adverse effects on host defense in the peritoneal cavity.

PMID- 9587350
TI  - Bacterial translocation from the biliary tract to blood and lymph in rats with
      obstructive jaundice.
AB  - BACKGROUND: The disruption of the hepatocyte tight junctions observed in biliary
      obstruction suggests altered permeability of the blood-bile barrier. In this
      study the role of biliary obstruction and increased biliary pressure on the
      translocation of bacteria from biliary tract to bloodstream and lymphatic system
      were evaluated. MATERIALS AND METHODS: Rats underwent distal bile duct ligation
      (BDL, n = 33) for two weeks or a sham celiotomy (n = 21). Seventeen of the 33 BDL
      rats underwent subsequent biliary decompression by a choledochojejunostomy (CJ).
      Two weeks after the final operation, a laparotomy was performed again and the
      CBD, the thoracic duct, and the caval vein were canulated. Next, a suspension
      containing 10(8) Escherichia coli/ml was retrogradely infused in the CBD for 5
      min at 5 or 20 cm H2O above the secretory biliary pressure. RESULTS: A higher
      biliary infusion pressure resulted in a significant increase of cfu E.coli per
      milliliter of blood in all the three groups (Sham, BDL, CJ). BDL rats showed
      significantly more bacterial translocation to the bloodstream than the shams.
      After biliary decompression, translocation normalized to the control levels. At 5
      cm H2O infusion pressure only one lymph culture was positive (CJ group). At 20 cm
      H2O overpressure, nine lymph cultures were E.coli positive (P = 0.03). These were
      found mainly in groups with a nonobstructed bile duct (Sham and CJ 40% vs BDL
      10%). CONCLUSION: Translocation of bacteria from biliary tract to bloodstream
      increased at higher intrabiliary pressures. Longstanding bile duct obstruction
      was an independent determinant for cholangiovenous reflux. Bacterial
      translocation to the lymphatic system did not parallel translocation to the
      bloodstream, although in the nonobstructed biliary tract, increased bacterial
      translocation to the lymphatic system was pressure related.

PMID- 9587351
TI  - Poloxamer 188 enhances functional recovery of lethally heat-shocked fibroblasts.
AB  - Damage to the cell membrane has been implicated as the primary event in the
      pathogenesis of heat shock, generally resulting in loss of cellular homeostasis
      and cell death. Thus a promising mode of therapy would involve the restoration of
      cell membrane integrity. Surfactant molecules, specifically triblock polymers
      such as Poloxamer 188 (P-188), possess the ability to self-aggregate into
      membrane-like structures in aqueous solutions and have been shown to restore
      membrane integrity. The objective of this study was to develop functional and
      morphological assays to determine whether treatment with P-188 after heat shock
      enhances the recovery of thermally damaged cells. Human foreskin fibroblasts were
      placed in sterile vials and heated by immersion in a calibrated water bath for
      various lengths of time at predefined temperatures. Cell recovery after heat
      shock was assessed using a functional assay based on the ability of the cells to
      contract fibroblast populated collagen lattices (FPCLs). Subsequent to heating,
      collagen lattices were prepared with control (no heat, no P-188) and heat shocked
      cells (with and without P-188). Our results indicate that treatment with low
      concentrations of P-188 after heat shock was effective in ameliorating both the
      morphological integrity and the contractile function of thermally damaged cells.
      Further, we observed that P-188 was most effective in improving the contractile
      ability of cells heat shocked at 45 degrees C; however, it had no influence on
      the contractility of cells exposed to higher temperatures. Our results suggest
      that there exists a threshold of thermal stress (45 degrees C for 20-60 min)
      beyond which treatment with low concentrations of P-188 (0.5 mg/ml) is
      ineffective in minimizing cell damage. Moreover, the results of our morphological
      assays indicate that cells treated with P-188 after heat shock maintain their
      cytoskeletal organization, whereas untreated cells exhibit filamentous actin
      depolymerization.

PMID- 9587352
TI  - Is gut the "motor" for producing hepatocellular dysfunction after trauma and
      hemorrhagic shock?
AB  - BACKGROUND: Although studies suggest that the gut may be the "motor" responsible
      for producing sepsis and multiple organ failure after injury, it is not known
      whether enterectomy prior to the onset of hemorrhage alters proinflammatory
      cytokines TNF and IL-6 and, if so, whether hepatocellular dysfunction and damage
      are prevented or attenuated under such conditions. MATERIALS AND METHODS: Under
      methoxyflurane anesthesia, an enterectomy in the rat was performed by excision of
      the duodenum, jejunum, and ileum. The rats were then bled to and maintained at a
      mean arterial pressure of 40 mm Hg until 40% of the maximal shed volume was
      returned in the form of Ringer's lactate. The animals were then resuscitated with
      four times the volume of shed blood with Ringer's lactate over 1 h. At 1.5 h
      after the completion of resuscitation, hepatocellular function [i.e., the maximal
      velocity (Vmax) and transport efficiency (Km) of indocyanine green (ICG)
      clearance] was assessed by an in vivo ICG clearance technique. Blood samples were
      taken for the measurement of TNF, IL-6, and liver enzymes (i.e., SGPT and SGOT).
      Cardiac output and microvascular blood flow were determined by ICG dilution and
      laser Doppler flowmetry, respectively. RESULTS: The increase in circulating
      levels of TNF but not IL-6 was prevented by enterectomy prior to hemorrhage. The
      reduced Vmax and K(m) and elevated SGPT and SGOT following hemorrhage and
      resuscitation, however, were not significantly affected by prior enterectomy.
      Moreover, enterectomy before hemorrhage further reduced hepatic perfusion.
      CONCLUSION: Since enterectomy prior to the onset of hemorrhage does not prevent
      or attenuate the reduced ICG clearance and elevated liver enzymes despite
      downregulation of TNF production, it appears that the small intestine does not
      play a significant role in producing hepatocellular dysfunction and injury
      following trauma and hemorrhagic shock.

PMID- 9587353
TI  - Supplemental dietary arginine accelerates intestinal mucosal regeneration and
      enhances bacterial clearance following radiation enteritis in rats.
AB  - BACKGROUND: Arginine is a dibasic amino acid with significant metabolic and
      immunologic, effects especially in trauma and stress situations. Arginine
      supplementation has been shown to promote wound healing and improve immune
      system. We designed a study to evaluate the effects of supplemental dietary
      arginine on intestinal mucosal recovery and bacterial translocation and bacterial
      clearance after induction of radiation injury in rats. METHODS: Twenty-one male
      Sprague-Dawley rats were subjected to a single dose of 1100 rads of abdominal X
      radiation. Rats were divided into three groups; the first group received diet
      enriched with 2% arginine, the second group with 4% arginine, and the third group
      with isonitrogenous 4% glycine. Rats were sacrificed 7 days after the radiation.
      Blood was drawn for arginine levels and mesenteric lymph nodes were harvested for
      quantitative aerobic and anaerobic cultures. Segments of ileum and jejunum were
      evaluated for villous height, number of villi per centimeter of intestine, and
      the number of mucous cells per villous. RESULTS AND CONCLUSIONS: Arginine is
      absorbed reliably from the gut following oral administration. Dietary 4% arginine
      supplementation enhanced bacterial clearance from mesenteric lymph nodes compared
      to 2% arginine and 4% glycine supplemented diet following radiation enteritis in
      rats. Four percent arginine resulted in clear improvement in intestinal mucosal
      recovery when compared to 2% arginine and 4% glycine after abdominal irradiation
      in rats.

PMID- 9587354
TI  - NADH videofluorimetry to monitor the energy state of skeletal muscle in vivo.
AB  - BACKGROUND: Reduction of the cellular energy state during ischemia of the limbs
      is an important determinant for development of necrosis. Since energy conversion
      in the mitochondria is based on electron transport from NADH to molecular O2, the
      NADH/NAD+ redox couple reflects the mitochondrial redox state and cellular O2
      requirement. The applicability of NADH videofluorimetry to monitor noninvasively
      changes in the energy state of intact resting skeletal muscle as a function of
      oxygenation was investigated in a rat model. MATERIALS AND METHODS: In
      mechanically ventilated rats (n = 6), NADH fluorescence images of the gracilis
      muscle were recorded under different oxygenation conditions. Induction of anoxic
      and ischemic hypoxia were verified by simultaneous measurement of tissue oxygen
      pressure and afferent blood flow. RESULTS: Anoxic hypoxia and ischemic hypoxia
      increased the NADH fluorescence intensity by 46.0 +/- 15.0 and 30.8 +/- 26.4%,
      respectively. The response time of NADH fluorescence intensity, tissue oxygen
      pressure, and afferent blood flow was similar during development of anoxic and
      ischemic hypoxia. Upon reperfusion and reoxygenation, however, NADH fluorescence
      intensity changed significantly earlier than tissue oxygen pressure as measured
      by an oxygen needle electrode. CONCLUSION: These results demonstrate that changes
      in NADH fluorescence intensity reflect oxygenation changes in intact skeletal
      muscle in vivo. Since NADH videofluorimetry, in contrast to oxygen needle
      electrode measurements, noninvasively visualizes temporal and regional changes in
      the energy state of skeletal muscle, this technique has the potential to improve
      clinical evaluation of ischemia/reperfusion injury and tissue viability.

PMID- 9587355
TI  - Is tissue oxygen tension during esophagectomy a predictor of esophagogastric
      anastomotic healing?
AB  - PURPOSE: The genesis of anastomotic leakage and late stenosis of
      esophagogastrostomy is still unknown, although minimal blood flow and tissue
      hypoxia of the gastric tube are discussed as main reasons. However, the changes
      in tissue oxygen tension (PtO2) on esophagogastric anastomoses have not yet been
      evaluated in the perioperative course. METHODS: Submucosal tissue oxygen tension
      (PtO2) was measured in 33 patients with cervical esophagogastrostomy during
      resection of esophageal carcinoma and reconstruction by a gastric tube.
      Measurements were taken close to the projected resection line and latter
      anastomosis using a Clark-type oxygen electrode. RESULTS: Mean baseline PtO2 was
      55.1 +/- 10.4 mmHg. Following the ligature of the vasa gastricae brevis and the
      left gastroepiploic artery (46.1 +/- 9.7 mmHg), the left gastric artery (34.8 +/-
      9.8 mmHg), and the pull up of the gastric tube, PtO2 decreased to 25.8 +/- 9.4
      mmHg. Anastomotic leakage occurred in 6 patients and late stenosis in 10
      patients. During the operation there was no significant evidence of decreased
      PtO2 levels in these two groups. Postoperative PtO2 levels showed a significant
      increase in patients with anastomotic leakage. CONCLUSION: A disorder in oxygen
      consumption may cause a significant increase of PtO2 in anastomotic tissue, which
      is associated with anastomotic leakage.

PMID- 9587356
TI  - Low-dose dopexamine's effect on lung and gut function after CPB in a sheep model.
AB  - OBJECTIVE: The lung injury regularly associated with cardiopulmonary bypass (CPB)
      may be linked to gut mucosal dysfunction occurring as the result of mucosal
      ischemia associated with nonpulsatile CPB. To examine this possibility we
      postulated that the weak-beta 2 agonist dopexamine would improve gut mucosal
      blood flow, thereby decreasing gut and lung dysfunction seen after CPB in sheep.
      METHODS: Anesthetized sheep had 2 h of hypothermic (24 degrees C), nonpulsatile
      CPB, and 60 min of cold, blood cardioplegic arrest. After warming they were
      separated from CPB for 2 h of reperfusion. Before and during CPB, dopexamine at 2
      micrograms/kg/min (n = 7) or saline (n = 7) were infused in a blinded fashion.
      Hemodynamic parameters were measured. Biatrial thromboxane B2 levels were
      obtained. Mesenteric arterial flow (QSMA), mucosal flow (Qmuc), FD-4 clearance
      (ClFD-4), and tonometric pHi were measured at baseline and 30-min intervals on,
      and after, CPB. RESULTS: After CPB, similar reductions in MAP were seen (P < 0.05
      vs. baseline), but heart rate and the mean pulmonary vascular resistance were
      significantly increased in the dopexamine animals (P < 0.05 vs. placebo). Plasma
      thromboxane was similarly increased in both groups after CPB (P < 0.05 vs.
      baseline), returning to baseline 1 h after CPB. The Qsma was not altered, but a
      statistically significant decrease in Qmuc and pHi occurred in both groups (P <
      0.05 vs. baseline). In both groups FD-4 clearance reached a peak 30 min after CPB
      (P < 0.05; dopexamine vs. baseline). After 2 h neither of these changes returned
      to control levels. CONCLUSIONS: In this ovine model, gut mucosal ischemia and
      increased permeability occur with hypothermic CPB, but dopexamine administration
      during CPB, compared to placebo, neither ameliorates these intestinal
      derangements nor reduces post-CPB lung pathophysiology.

PMID- 9587357
TI  - Perioperative continuous hepatocyte growth factor supply prevents postoperative
      liver failure in rats with liver cirrhosis.
AB  - Insufficient regeneration and dysfunction of cirrhotic liver following partial
      hepatectomy often make the resection extremely vulnerable to postoperative liver
      failure, which frequently leads to multiple organ failure. Hepatocyte growth
      factor (HGF), first identified as the most potent mitogen for primary
      hepatocytes, not only stimulates hepatic regeneration but also accelerates liver
      function, improves fibrosis, and protects liver cells against injury. Therefore,
      we investigated the ability of a continuous supply of HGF to cirrhotic livers to
      prevent postoperative liver failure in rats. After liver cirrhosis was induced in
      40 rats by the intraperitoneal injection of dimethylnitrosamine (DMN) for 4
      weeks, fibroblasts genetically modified to secret rat HGF or control fibroblasts
      were implanted in the spleens of 20 syngenic rats per group to supply HGF
      continuously and directly to the cirrhotic livers. Two weeks after the
      implantation, all rats underwent a 30% hepatectomy. The HGF administration
      significantly improved liver fibrosis at the time of operation, attenuated the
      postoperative hepatic damage on histological examination, markedly accelerated
      the liver regeneration at 24 h after the hepatectomy. The blood chemical analysis
      indicated that HGF significantly suppressed postoperative liver failure. Most
      importantly, the HGF treatment significantly improved the survival rate of the
      rats at 48 h after the hepatectomy. The perioperative continuous supply of HGF
      from the spleen effectively prevented liver failure following resection of
      cirrhotic livers in rats.

PMID- 9587358
TI  - Gluconeogenesis and phosphoenergetics in rat liver during endotoxemia.
AB  - BACKGROUND: During endotoxemia, glucose and energy metabolism varies depending on
      the stage, severity, and other conditions. In this study, gluconeogenesis from
      13C-labeled alanine and phosphoenergetic state in rat liver during the acute
      phase of endotoxemia were concurrently observed by in vivo 13C and 31P NMR
      spectroscopy in a noninvasive manner. MATERIALS AND METHODS: Lipopolysaccharide
      from Escherichia coli (10 mg/kg) was injected intravenously followed by infusion
      of [3-13C]alanine. In vivo 13C and 31P NMR spectra were alternately collected for
      90 min with a 2.0 Tesla CSI Omega System. RESULTS: In our experimental model,
      endotoxin increased the pulse rate without decreasing the blood pressure and
      elevated the blood sugar level, which suggests the so-called hyperdynamic state.
      Even under such conditions, a slight, but significant, impairment of the
      phosphoenergetic state in the liver (a decrease in ATP and an increase in Pi) was
      detected with 31P NMR spectroscopy. The 13C peaks of glucose C6 and Glu/Gln C2 of
      the liver in endotoxemia were significantly lower than those of the control,
      despite hyperglycemia in endotoxemia. CONCLUSIONS: NMR spectroscopic studies
      suggest that the endotoxin caused the inhibition of gluconeogenic activity from
      the infused [3-13C]alanine and the TCA cycle accompanied by a deterioration in
      the phosphoenergetic state even in the hyperglycemic phase. Since the blood sugar
      level might be influenced by the systemic utilization of glucose, such direct
      measurements should prove important in the in vivo evaluation of glucose and
      energy metabolism in the liver.

PMID- 9587360
TI  - [Methylation and cancer].

PMID- 9587359
TI  - An in vivo model of human proliferative scar.
AB  - BACKGROUND: Many aspects related to the biology and the effective therapy of
      proliferative scars have remained undefined, in part due to a lack of an accurate
      and reproducible animal model with which to systematically study them. This
      report describes a new model for investigating the pathophysiology and
      manipulation of human proliferative scars. MATERIALS AND METHODS: Human
      proliferative scars (n = 86) were explanted into flaps based on isolated vascular
      pedicles in congenitally athymic rats. Serial analysis of the structural and
      functional integrity of the explanted scars was performed by microscopy and by
      measurement of human procollagen type III peptide (PIIIP) production, human
      factor VIII immunostaining, and in vitro cellular proliferation. RESULTS: By
      these methods, both fibroblastic and epithelial components of explanted scar
      specimens retained the histologic characteristics of original human scar
      specimens, for up to 12 months. Over the same duration, scar explants continued
      to have high levels of human PIIIP, comparable to those found in original
      surgical specimens. The microvasculature of scar explants demonstrated a double
      basement membrane, with no staining of human factor VIII in the inner capillary
      endothelial layer, suggesting that host vessels were growing into ghost vessels
      of the human donor scar. Human factor VIII staining decreased over time.
      Fibroblasts cultured from explanted scar demonstrated less aggressive growth
      characteristics than those from original surgical specimens. CONCLUSIONS: This
      new model is the first to allow such long-term maintenance and serial evaluation
      of human proliferative scar on an accessible, isolated vasculature. It may prove
      useful in further defining the biology and therapy of this widespread pathologic
      process.

PMID- 9587361
TI  - [A comparative study of metastatic patterns of ductal and lobular carcinoma of
      the breast from two matched series (376 patients)].
AB  - Five studies comparing metastatic patterns of lobular and ductal carcinoma have
      reported conflicting results. These results are based on the evaluation of
      heterogeneous groups, without taking clinical differences into account. The aim
      of this clinical study is to compare metastatic patterns of matched ductal and
      lobular carcinomas. One hundred eighty-eight lobular carcinomas were matched with
      188 ductal carcinomas who showed identical ages, menopausal status, TNM, and
      dates of treatment. Hepatic, lung and brain metastases are more frequent in
      ductal carcinoma. Metastases to the gastrointestinal system, gynecologic organs,
      and peritoneum are more characteristic of lobular carcinoma. Life table analysis
      of overall and disease free survival shows no significant differences. The
      metastatic patterns of ductal and lobular carcinomas are different, and
      physicians should be aware that the classical staging of the breast cancer is not
      fit to lobular carcinoma. fit to lobular carcinoma. Could we define patients
      presenting high metastatic risks? Could we use CA. 125, sonography, laparoscopy
      in the staging? Should we change the whole therapeutic approach of lobular
      carcinoma?

PMID- 9587362
TI  - [Small cell carcinoma of the esophagus. Report of five cases with review of the
      literature].
AB  - Small-cell carcinomas of the esophagus are a rare and aggressive tumors with
      early widespread dissemination. Despite the use of different therapeutic
      modalities, the prognosis remains poor. Between 1993 and 1995, 5 patients with
      small-cell carcinoma of the esophagus were treated at Rene-Gauducheau Center,
      representing 2.8% of all esophageal malignancies diagnosed during this period.
      Three patients presented with limited disease while 2 patients had distant
      metastases at the time of diagnosis. Primary treatment consisted of
      polychemotherapy in all patients and a complete response was observed in three
      cases. These 3 patients had received subsequent radiotherapy, and endoesophageal
      brachytherapy in 2 cases. In this article, we report our experience of patients
      with this tumor and attempt to make comparisons with the cases published in the
      literature, regarding location, symptomatology, histopathologic diagnosis and
      treatment of this tumor. We conclude that the optimum treatment seems to be the
      same as for small-cell carcinoma of the lung, a multidrug combination
      chemotherapy regimen used alone or with sequential radiation.

PMID- 9587363
TI  - [Secondary head and neck osteosarcoma following treatment of undifferentiated
      nasopharyngeal neoplasms (UCNT)].
AB  - Secondary tumours after radio and/or chemotherapy are mainly of hematopoietic
      (acute non lymphoblastic leukemia, non-Hodgkin lymphoma) or soft tissue lineage
      previously described most frequently after breast cancer and Hodgkin disease
      treatment with radio and/or chemotherapy. We report two cases of classical
      osteosarcoma's observed 9 and 3 years after treatment for UCNT with combined
      radiotherapy and alkylant-based adjuvant chemotherapy in one case and exclusive
      loco-regional irradiation in the second case.

PMID- 9587364
TI  - [Cancer localisation in men and women aged over 50 in Cameroon].
AB  - The aim of this study was to present the sites of cancers diagnosed in men and
      women aged 50 years and above in Cameroon. From the registries of the pathology
      laboratory of the Yaounde Central Hospital which at the national level receives
      the majority of samples sent for histopathology analysis, we recorded all cases
      of cancers diagnosed in people aged 50 years and above, during the period from
      1st January 1987 to 31st August 1996 (9 years 8 months). 1,925 cancers were
      recorded: -1,005 of these (52.2%) were issued from men aged fifty years and
      above. These 1,005 cancers came from seventeen sites, the most common being:
      liver (226 cases = 22.49%), prostate (222 cases = 22.09%), skin (195 cases =
      19.40%) and ENT (100 cases = 9.95%); that made 73.93% (above 3/4) of cancers
      observed in men aged fifty years and above from this study. -920 of these (47.8%)
      were diagnosed from women aged fifty years and above. These 920 cancers came from
      twenty-two sites, the most common being: uterine cervix (292 cases = 31.74%),
      breast (170 cases = 18.48%), skin (111 cases = 12.07%) and liver (90 cases =
      9.78%); that made 72.07% (about 3/4) of cancers observed in women aged fifty
      years and above, from this study.

PMID- 9587365
TI  - [Inhibition of telomeres and telomerase. Seeking for new anticancer drugs].
AB  - Human telomeres are guanine-rich regions (TTAGGG) located at the end of
      chromosomes that protect them against aberrant recombination and protect DNA from
      exonuclease degradation. Telomeres maintenance is performed by telomerase, a RNA
      dependent DNA polymerase. Telomerase is over-expressed in a large number of
      cancers that have short telomeres whereas it is not expressed in somatic cells
      that have long telomeres. Therefore, this differential gives a rational for
      further evaluation of telomerase and telomeres as targets for identification of
      new anticancer drugs. Current strategies aim to identify new drugs with specific
      activity against telomerase and telomeres. In this review we will discuss the
      biological and clinical approaches as well as relevant tumor models for studying
      the biological effects of telomerase inhibition and telomere targeting in vitro
      and in vivo.

PMID- 9587366
TI  - [Recombinant immunotoxins and chimeric toxins for targeted therapy in oncology].
AB  - Immunotoxins and chimeric toxins are hybrid molecules constituted of antibodies,
      growth factor or cytokines coupled to peptide toxins. They are designed to
      selectively eliminate tumor cells. Some of these chimera have been shown to
      induce complete tumor regressions of human tumor xenografts in immunodeficient
      mice. In clinical trials, higher anti tumor response were observed in lymphoma,
      brain tumor, breast and colon cancers. Problems arose with normal tissue toxicity
      and the production of neutralising antibodies. Should the latest recombinant
      toxins conceived by rationale designed, solved these problems, chimeric toxins
      would be an alternative approach to target tumor cells and vascular endothelial
      cells in solid tumors.

PMID- 9587367
TI  - [TSG101 and breast cancer: a correctly named tumor-suppressor gene?].
AB  - In January 1997, PCR genomic analysis of the TSG101 gene showed frequent large
      intragenic deletions. The investigators used a small cohort of sporadic breast
      cancers. Li et al. proposed human TSG101 as a breast tumor suppressor gene. Since
      then, several teams have worked on large series of breast cancers, using a
      variety of techniques. They have shown that intragenic deletion, if it exists at
      all, is rare. Is TSG101 a tumor gene or an impostor?

PMID- 9587368
TI  - [The postman always rings twice, so does the receptor].

PMID- 9587369
TI  - [How to read a scientific article].
AB  - Medical literature is too prolific and user's guides are necessary to extract
      useful information for optimal treatment of our patients. The goal of this paper
      is to help doctors find relevant articles and to read them efficiently for
      applying the results to their patients. An excerpt has been written concerning
      the subject by the Mac Master team and the members of the Cochrane Collaboration
      in the JAMA, the BMJ and on the Internet: a web site is now devoted to user's
      guides to medical literature. Simple rules facilitating access to relevant papers
      and interpretation of the results have been given. They have been applied to
      oncology, especially to papers concerning effectiveness of therapeutic
      interventions. It is essential that doctors use simple rules and learn how to
      select relevant articles and understand and use them to treat their patients
      according to Evidence-Based Medicine Group.

PMID- 9587370
TI  - [Role of radiotherapy in benign diseases].
AB  - Radiation therapy of benign diseases represent a wide panel of indications. Some
      indications are clearly identified as treatment of arteriovenous malformations
      (AVM), hyperthyroid ophtalmopathy, postoperative heterotopic bone formations or
      keloid scars. Some indications are under evaluation as complications induced by
      neo-vessels of age-related macular degeneration or coronary restenosis after
      angioplasty. Some indications remain controversial with poor evidence of
      efficiency as treatment of bursitis, tendinitis or Dupuytren's disease. Some
      indications are now obsolete such as warts, or contra-indicated as treatment of
      infant and children.

PMID- 9587371
TI  - [Indications and results of radical prostatectomy].
AB  - Radical prostatectomy is the surgical curative treatment of localized prostate
      cancer. The survival is good in young patients (< 70) with T2 N0M0 tumors and
      more than 10 year's life expectancy. Side-effects are urinary incontinence,
      impotence and anastomosis stricture. Quality of life should be considered as an
      important factor for the choice of the patient between radical prostatectomy,
      radiotherapy and follow-up.

PMID- 9587372
TI  - [Localized prostatic adenocarcinoma: role of pelvic radiotherapy following
      radical prostatectomy].
AB  - Radical prostatectomy after pelvic lymphadenectomy is an effective treatment for
      patients with T1-2 pN0 adenocarcinoma of the prostate. However, pathologic
      analysis of resected tissue reveals that in 20 to 40% of clinical stage B
      lesions, the tumour has extended locally beyond the prostate. This infra-clinical
      disease may be the origin of local relapse. Radiation oncologists are often asked
      to deliver post-operative irradiation. There is sufficient evidence in the
      literature that postoperative radiation therapy can improve local control rate
      for patients with pT3 pN0 adenocarcinoma of the prostate; however, the effect of
      this radiotherapy on survival in this category of patients remains unclear. It is
      the reason why randomised clinical trials have been implemented for investigating
      the role of pelvic external irradiation with respect to the effects on local
      control, acute and late morbidity, overall survival and cancer-related survival,
      and for better defining the selective indications of radiotherapy, regarding
      pathological data.

PMID- 9587373
TI  - [Indications and results of exclusive radiotherapy in early prostatic
      adenocarcinoma].
AB  - Prostate adenocarcinoma incidence are rising rapidly, especially in early stages.
      Even if some of these carcinomas may be latent or slow growing either
      spontaneously or under hormonal therapy, most patients 75 years old or less
      presenting a localized tumor, T1b-c, T2, T3, N0, M0, whatever the grading, will
      require treatment with curative intent: radical prostatectomy, external beam
      radiation therapy (ERT) and/or brachytherapy. After ERT limited to the prostate
      or including seminal vesicles and/or pelvic lymph nodes, the overall survival and
      the survival without clinical evolution at 5, 10 and 15 years are good. However
      survival rates without biochemical evolution are about 30% lower and 70% or less
      at 5 years for the more favorable group (T < or = T2a and Gleason < 7 and PSA <
      10 ng/mL). Brachytherapy alone yields good results for the same favorable group.
      In the unfavorable group (T > or = 2c and Gleason > or = 7 and PSA > or = 20
      ng/mL), adjuvant hormonal therapy improves survival. Conformal radiation therapy
      allows an increase in dose to the tumor by about 15% without increasing
      complications. It can increase the biological remission rate in the intermediate
      group (T < or = 2a or Gleason > or = 7 or PSA > or = 20 ng/mL).

PMID- 9587375
TI  - [New biological prognostic factors of soft tissue sarcoma. SFOP (Societe
      francaise d'oncologie pediatrique)].
AB  - Malignant tumors of soft tissue constitute a very heterogeneous group of tumors
      which is composed of more than 50 different entities derived from either the
      mesenchyme or the neuroectoderm. Diagnostic problems can be linked to the
      difficulty to firmly establish the diagnosis of malignancy and to the precise
      determination of the type of sarcoma. The prognostic is largely dependent on
      local and distant extension of the cancer. The study of the genotype of tumor
      cells has enabled the detection and characterization of genetic alterations.
      These alterations, frequently chromosome translocations, are specific markers for
      subgroups of tumors and can thus be of clinical relevance. These markers can be
      detected by cytogenetic, in situ hybridization or molecular biology techniques.
      The specificity of these alterations for tumor cells and the possibility to
      detect them with the highly sensitive polymerase chain reaction (PCR) technique
      have enabled development of tests aimed at the detection of tumor cells within
      potential metastatic sites.

PMID- 9587374
TI  - [Combination of radiotherapy and hormonotherapy in locally advanced cancers of
      the prostate].
AB  - The long-term results of external irradiation in locally advanced prostate cancer
      are poor: relapses are local or distant from infra-clinical disease present at
      diagnosis. Three clinical randomized trials have shown that hormonotherapy with
      LH-RH analogue with or without antiandrogen has improved: disease-free survival,
      local recurrence-free survival and metastasis-free survival (P < 0.001). The
      EORTC trial 22863 has shown a significant improvement of the overall survival (P
      = 0.001), with an LH-RH analogue (goserilin acetate, Zoladex) was administered
      the first day of irradiation and then every 4 weeks for 3 years; for the RTOG
      trial 85-31 the same LH-RH analogue was administered during the last week of
      irradiation and given until relapse increases survival of patients with poor
      differentiated tumours with a Gleason score ranging from 8 to 10 (P = 0.03).
      Adjuvant hormonal treatment with an LH-RH analogue is recommended, but the
      optimal duration of the treatment remains unclear.

PMID- 9587376
TI  - [New surgical techniques in soft tissue sarcoma].
AB  - PURPOSE: To elaborate a new classification of surgery of soft tissue sarcoma
      (STS). PATIENTS AND METHODS: This was a multicentre study. Purely descriptive
      terms of surgery of STS have been established. The classification results in a
      synthesis of surgery terms and conclusion of the pathological report defining the
      resection (R): R0 = in sano, R1 = microscopic residual disease, R2 = macroscopic
      residual disease. Validity of the terms has been evaluated by questionnaire,
      first concerning previous operations, then prospectively during 15 months on the
      following operations. RESULTS: One hundred and seventy six operating forms
      established prospectively by eight centres were analyzed. The majority of
      surgeons were satisfied with the new items. Most of them judged the terms
      appropriate to surgery. In 96 cases, confrontation between the surgical terms and
      pathological items was made. Concordance between them was found in 2/3 of the
      cases. Discordance was observed essentially in cases of re-excision. In all 96
      cases the synthesis was judged reliable, permitting treatment adaptation. The
      study is ongoing. Following propositions of participants, modifications of the
      surgery terms are included. CONCLUSION: Subject to confirmation of these
      promising results, the proposed classification should contribute to optimize
      treatment of STS.

PMID- 9587377
TI  - [Role of radiotherapy in soft tissue sarcoma].
AB  - Radiation therapy is generally used as a surgical adjuvant in the treatment of
      soft tissue sarcomas. Postoperative external beam irradiation is the most
      commonly applied treatment. The majority of retrospective studies have suggested
      that radiation therapy could reduce the incidence of local recurrence. Radiation
      is recommended in case of deep tumor location, inadequate surgical margins and
      grade 3 tumor. A total dose of 55 to 65 Gy using large volume with initial field
      margin of 5 cm are recommended. Radiation therapy can also be delivered in
      preoperative fashion, but the majority of the studies have reported a higher
      wound complication rate. The value of brachytherapy for reducing the risk of
      local recurrence has been demonstrated in a randomized trial, especially for
      patients with high grade tumors. The combination of external radiation (40 to 45
      Gy) and brachytherapy (15 to 20 Gy) seems to be the optimal adjuvant local
      strategy.

PMID- 9587378
TI  - [Adjuvant chemotherapy of soft tissue sarcoma].
AB  - The role of chemotherapy in the treatment of operable soft tissue sarcomas is
      still debatable. In high-grade tumors, randomized trials using adjuvant
      chemotherapy have resulted in controversial results. A recent meta-analysis
      showed a higher median disease-free survival in groups with chemotherapy compared
      to controls. Doxorubicin, ifosfamide and dacarbazine are the majors drugs. Their
      combination in adjuvant treatment is currently being investigated. Neoadjuvant
      chemotherapy has allowed conservative surgery in initially unoperable tumors, but
      its role in primarily operable tumors remains to be defined.

PMID- 9587379
TI  - [From biology to radiotherapy: current state and future perspectives].

PMID- 9587380
TI  - [Predictive tests of response to radiotherapy. Assessment and perspectives in
      1997].
AB  - The potential tailoring of radiotherapy modalities to the biological
      characteristics of individual tumours and normal tissues appears to be an
      exciting way to improve the therapeutic, ratio in radiation therapy patients.
      Numerous assays have been proposed to provide the clinician with the biological
      information necessary to predict the outcome after irradiation and to guide the
      treatment prescription, but none of them has made its way to daily practice.
      Major difficulties are due to the technical burden of the procedures, the poor
      characterization of the assayed cells, and, moreover, the high complexity of
      tumour and normal tissues biology. The present paper reviews the present status
      of the assessment of tumour cells radiosensitivity, proliferation and
      oxygenation. Research remains extremely active in the field of biological
      predictors of response to irradiation. Future steps forwards are expected from
      progress in the available technologies, (re-)discovery of apoptosis and
      investigation of normal tissue tolerance.

PMID- 9587381
TI  - [Modulation of cellular response to ionizing radiation: towards new molecular
      targets?].
AB  - Recent advances have been made in the understanding of molecular events following
      cellular exposure to ionizing radiations, suggesting that new molecular targets
      could be used to modulate radio-induced cellular response, including genes and
      their encoded protein involved in DNA repair, signal transduction, apoptosis and
      cell cycle regulation. These potential molecular targets include some radio
      induced cytokines and growth factors that could modulate radiation response in
      irradiated normal tissues (TGF beta). In addition, in order to increase tumor
      cell lethality after irradiation exposure, two promising approaches have been
      recently explored, including firstly the modulation of radiation-induced
      apoptosis via the transfer of genes involved in the regulation of apoptosis
      (p53), and secondly the modulation of double strand break DNA repair.

PMID- 9587382
TI  - [Early cell response to radiation].
AB  - The early steps of cellular radiation response have been investigated using a
      linear electron accelerator operated in a split-dose mode, in such a way that the
      time intervals between pulse exposures to relativistic electrons ranged from
      fractions of a second to a few minutes. The initial dose brought about large,
      synchronous changes in radiation sensitivity and generated a tetraphasic, W
      shaped time-dependent profile of cell survival upon the second radiation
      exposure. While this time-related process was observed in most cell lines
      investigated, its kinetic parameters varied significantly from one cell line to
      the other. The number of DNA strand breaks (neutral and alkaline DNA filter
      elution) and the level of apoptosis (gel electrophoresis and flow cytometry)
      induced at the different phases of the time-dependent profile showed no
      relationship with the W-effect. It is presently hypothesized that mechanisms
      involved in molecular recognition of radio-induced lesions and initiation of
      genomic instability play a major role in this effect. Whatever the mechanism
      involved, the split-dose irradiation in the range of seconds enables dissecting
      the early steps of radiation response. The relevance of the W-effect to radiation
      therapy and technical drawbacks are discussed.

PMID- 9587383
TI  - [Intraoperative radiotherapy in 1997].
AB  - Intra Operative Radiation Therapy (IORT) has been routinely used for the past 20
      years. It is a feasible treatment, with a reasonable cost and an acceptable acute
      and late toxicity. There is so far no strong randomized trial demonstrating that
      IORT can improve overall survival. Nevertheless, in many institutions it is
      recognized as an efficient treatment in selected patients. In case of locally
      recurrent disease an incomplete gross resection is often the only choice; IORT in
      such a situation has led to very encouraging results. For locally advanced deep
      seated primary tumors IORT seems to improve local control. In the near future
      IORT should be used on a larger and stronger basis. The manufacturing of new
      mobile linac should allow more surgeons to perform IORT and to conduct clinical
      trials to confirm the present indications in cancers with high local malignancy.

PMID- 9587384
TI  - [Exchange of medical imaging and data information in radiotherapy: needs, methods
      and current limits].
AB  - Extension of the image network within radiotherapy departments provides the
      technical infrastructure which is made necessary by the rapid evolution of
      techniques in the field of diagnosis and treatment in radiotherapy. The system is
      aimed at managing the whole set of data (textual data and images) that are needed
      for planning and control of treatments. The radiotherapy network addresses two
      objectives: managing both the information necessary for treatment planning
      (target volumes definition, planning dosimetry) and the control of all parameters
      involved during the patient's treatment under the treatment unit. The major
      challenge is to improve the quality of treatment. Multimodal imaging is a major
      advance as it allows the use of new dosimetry and simulation techniques. The need
      for standards to exchange medical imaging information is now recognized by all
      the institutions and a majority of users and manufacturers. It is widely accepted
      that the lack of standard has been one of the fundamental obstacles in the
      deployment of operational "Picture Archiving Communication Systems". The
      International Standard Organisation Open System Interconnection model is the
      standard reference mode used to describe network protocols. The network is based
      on the Ethernet and TCP/IP protocol that provides the means to interconnect
      imaging devices and workstations dedicated to specific image processing or
      machines used in radiotherapy. The network uses Ethernet cabled on twisted-pair
      (10 BaseT) or optical fibres in a star-shaped physical layout. Dicom V3.0
      supports fundamental network interactions: transfer of images (computerized
      tomography magnetic resonance imaging query and retrieve of images), printing on
      network attached cameras, support of HIS/RIS related interfacing and image
      management. The supplement to the Dicom standard, Dicom RT, specifies five data
      objects known in Dicom as Information Object Definition for relevant
      radiotherapy. Dicom RT objects can provide a mean for standardized transfer of
      most of the information wich circulates in a radiotherapy department. A wide
      range of device types are represented, (treatment planning systems, portal
      imaging devices, linear accelerators, recording and verifying systems,
      conventional and virtual simulators). There will be additions and perhaps new
      developments in dataflow management, more complete integration with HIS/RIS
      system and printing, but the lion's share of the work has now been done. A
      project to integrate some security features into the Dicom protocol has begun.

PMID- 9587385
TI  - [Therapeutic approaches of adenocarcinoma of the exocrine pancreas. Trends in
      1997].
AB  - The prognosis for adenocarcinoma of the pancreas remains poor. Besides surgical
      treatment of operable localised tumours, many questions are raised: what is the
      role of adjuvant therapies, chemo-radiotherapy, pre-operative or post-operative
      combinations, and what is the role of radiotherapy or chemo-radiotherapy during
      surgery? In the case of inoperable tumours, there is no consensus on the role and
      the value of various protocols whose toxicity is generally high. Improvements in
      treatment must come from a better understanding of the role of various prognostic
      factors (biological markers in particular).

PMID- 9587386
TI  - [Surgical treatment of cancer of the pancreas].
AB  - Resection of the pancreas is still the only way to cure patients with pancreatic
      cancer. Morbidity and mortality rates following pancreatico-duodenectomy for
      adenocarcinoma of the pancreas have decreased. Survival has improved during the
      past several decades.

PMID- 9587387
TI  - [Role of adjuvant chemoradiotherapy in the therapeutic strategy of exocrine
      adenocarcinoma of the pancreas].
AB  - The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival
      rate lower than 5%. Resection, the gold standard treatment, can be performed in
      less than 10% of patients. Following surgery, the median survival is 12 months
      for the most favorable patients. Concomitant chemoradiation, as an adjuvant
      treatment is superior to surgery alone, in terms of survival, controlled trials
      are currently performed. Neoadjuvant chemoradiation is a new approach,
      potentially able to increase survival and resection rate. This work justifies the
      role of these schemes, in terms of modalities and potential advantages.

PMID- 9587388
TI  - [Locally advanced adenocarcinoma of the pancreas: current therapeutic
      modalities].
AB  - Pancreatic cancer still have bad prognosis. At the time of diagnosis, less than
      10% of patients can undergo surgery with an overall 5-year survival rate of less
      than 2%. For patients with localized pancreatic adenocarcinoma, the combination
      of radiation therapy and chemotherapy has been shown to control symptoms and to
      enhance patient survival. This treatment should be proposed to all the patients
      with good performance status and without icterus. Pain management should be
      optimized and often need morphinic and co-antalgic (anticonvulsivants, steroids)
      consumption. The celiac plexus block with alcohol gives an excellent pain relief
      and should be more frequently used.

PMID- 9587389
TI  - [Fight against cancer of the exocrine pancreas: stagnation or progress? The point
      of view of the Fondation francaise de cancerologie digestive (FFCD)].
AB  - This paper updates recent trends concerning ductal pancreatic cancer. Knowledge
      of the cellular mechanisms has improved, and new developments in imaging allow a
      more accurate staging. Although operative mortality sharply decreased during
      these last 15 years, the prognosis of pancreatic carcinoma remains dismal, due to
      late diagnosis, as only one out of ten patients is considered for curative
      resection. Therapeutic research groups, and among them the Fondation francaise de
      cancerologie digestive (FFCD), do their best to develop new therapeutic
      strategies, including post-operative or preferentially pre-operative radio
      chemotherapeutic adjuvant treatments, and to improve chemotherapy in metastatic
      cancers.

PMID- 9587390
TI  - [Computed tomography option on simulator: a 14-month use at the Orleans hospital
      radiotherapy department].
AB  - The purpose was to evaluate the use of the CT option for simulator during a 14
      month period in the radiotherapy department. The CT option has been adapted on
      the Philips simulator SL23. The virtual tunnel diameter is 92 cm which allows
      slice acquisition regardless of the contention device used. This system is
      connected to the treatment planning system through an Ethernet link. Three fields
      of view are available which cover the standard radiotherapy use. Four hundred and
      twenty-seven patients benefited from this system over a 14-month period of use.
      The number of slices acquired per patient regularly increased. The use of the
      system was rapidly extended to all the standard treatments. Those slices were
      also used as additional information for these high technology treatments. The
      good quality of the images and the reliability of this system involved a rapid
      integration in the treatment preparation procedure. It will not replace the use
      of the scanner but will significantly improve the treatment quality.

PMID- 9587391
TI  - [Virtual simulation: means and methodology].
AB  - State of the art imaging and computer systems coupled with the development of
      superior visualisation and multiplane reconstruction software have opened new
      perspectives in treatment planning. "Virtual simulation" of the irradiation
      technique allows definition in 3D of the optimised geometrical characteristics of
      the treatment beams with respect to anatomical structures of the patient. One can
      then visualise the beam direction and target volume coverage in the "virtual
      patient", leading to very precise radiotherapy. However, this "three dimensional"
      approach requires not only technical means, but also a methodology and an
      appropriate system of quality assurance for each step of the treatment planning,
      as well as significant multidisciplinary input.

PMID- 9587392
TI  - [Practice of virtual simulation at the Saint-Andre hospital].
AB  - PURPOSE: Prospective evaluation of a virtual simulation technique. PATIENTS AND
      METHODS: From September 1993 to February 1997, 343 patients underwent radiation
      therapy using this technique. Treated sites were mostly: brain (132), rectum
      (59), lung (43), and prostate (28). A CT-scan was performed on a patient in
      treatment position. Twenty-five to 70 jointive slices widely encompassed the
      treated volume. The target volume (CTV according to ICRU 50) and often critical
      organs were controured, slice by slice, by the radiation oncologist. Beams
      covering the CTV plus a security margin (PTV) were placed on the "virtual
      patient". Digital radiographs were reconstructed (DRR) as simulator radiographs
      for each field. Thus, the good coverage of PTV was assessed. Fields and beam
      arrangements were further optimized. Definitive isocenter was then placed using a
      classical simulator. Perfect matching of DRR and actual simulator radiographs had
      to be obtained. RESULTS: Nineteen patients presented grade 3, and 1 grade 4 acute
      radiation effects. With a median follow-up of 18 months, five patients suffered
      from grade 3, and one from grade 4 complications. Fifty-five patients had tumor
      recurrence in the treated volume, and 19 had marginal relapse. CONCLUSION: In our
      department, virtual simulation has become a routine technique of treatment
      planning for deep-seated tumors. This technique remains time-consuming for
      radiation oncologists: about 2 hours. But it stimulates reflexion on anatomy,
      tumor extension pathways, target volumes; and is becoming an excellent
      pedagogical tool.

PMID- 9587393
TI  - Bone marrow transplantation for autoimmune diseases.
AB  - Bone marrow transplantation (BMT) is now becoming a powerful strategy for the
      treatment of patients with autoimmune diseases. Using various animal models for
      autoimmune diseases, we have previously found that allogeneic BMT (not autologous
      BMT) can be used to treat autoimmune diseases such as systemic lupus
      erythematosus (SLE), rheumatoid arthritis (RA), immune thrombocytic purpura,
      insulin-dependent diabetes mellitus (IDDM), chronic glomerulonephritis, and
      certain types of non-insulin-dependent diabetes mellitus. In contrast, we have
      found that the transplantation of T-cell-depleted bone marrow cells or partially
      purified hemopoietic stem cells (HSCs) from autoimmune-prone mice to normal mice
      leads to the induction of autoimmune diseases in the recipients. These findings
      have recently been confirmed even in humans; autoimmune diseases such as RA, SLE,
      multiple sclerosis, and Crohn's disease were resolved after allogeneic BMT.
      However, there have recently been reports on the rapid recurrence or persistence
      of autoimmune diseases after autologous BMT. Conversely, the adoptive transfer of
      autoimmune diseases such as myasthenia gravis, IDDM and Graves' disease by
      allogeneic BMT from donors to recipients has been reported. Based on these
      findings, we have proposed that autoimmune disease is 'a stem cell disorder'. To
      clarify the differences between normal and abnormal HSCs, we have established a
      new method for purifying HSCs. Using this method, we purified HSCs from normal
      and autoimmune-prone mice and compared the former with the latter. We have found
      that a major histocompatibility complex (MHC) restriction exists between normal
      HSCs and stromal cells, whereas there is no MHC restriction between abnormal HSCs
      and stromal cells either in vivo or in vitro; abnormal HSCs proliferate even in
      allogeneic environments. Abnormal HSCs thus appear to be more resilient than
      normal HSCs. In humans, BMT across MHC barriers has had a low success rate as a
      consequence of (1) graft-versus-host disease (GVHD), (2) graft rejection and (3)
      incomplete recovery of T cell functions. However, we have found that such
      problems can be overcome in mice. GVHD can be prevented if T-cell-depleted bone
      marrow cells are used. Graft rejection can be prevented by bone grafts to recruit
      donor stromal cells, since, as we have found, an MHC restriction exists between
      HSCs and stromal cells. In addition, we have found that stromal cells migrate
      from the bone marrow to the thymus, where they become engaged in positive
      selection. Therefore, the bone grafting to recruit donor stromal cells leads to a
      complete recovery of T cell functions, since T cells, which are positively
      selected by donor stromal cells in the thymus, can cooperate with donor B cells
      and antigen-presenting cells. In humans, it is well known that the success rate
      of BMT in patients more than 45 years old is low. Recently, we have found that
      the low success rate is due to the aging of the thymus, and that BMT plus
      embryonal thymus grafts can be used to treat late-onset autoimmune diseases in
      MRL/+ mice. Based on these findings, we would like to suggest that the
      transplantation of the embryonal thymus in conjunction with BMT will become a
      valuable strategy for treating older patients with various intractable diseases,
      including autoimmune diseases. We believe that similar conditions (to permit
      successful allogeneic BMT) to those in mice will be realized in humans in the
      near future.

PMID- 9587394
TI  - Approaches to induction therapy with adult acute myeloid leukaemia.
AB  - Induction therapy of acute myeloid leukaemia (AML) with standard-dose
      chemotherapy will result in approximately 64% of patients achieving a complete
      remission (CR). New drugs which are active in induction therapy in randomised
      clinical trials are etoposide, idarubicin and high dose cytarabine.
      Intensification of induction treatment with etoposide or high-dose cytarabine
      does not appear to alter the CR rate but prolongs remission and has some impact
      on survival. High-dose cytarabine in induction combinations increase relapse-free
      survival compared to standard approaches. These induction results appear to
      parallel results obtained with post-remission therapies intensified with high
      dose cytarabine. These studies provide clinical evidence that intensified
      induction with cytarabine in AML influences subsequent outcome but is more toxic,
      gives more profound myelosuppression post-remission and has benefit confined to
      younger patients.

PMID- 9587395
TI  - Safety screening of drugs in cancer therapy.
AB  - Development of new drugs requires a thorough investigation of efficacy and safety
      of pharmaceuticals. The potential risks and benefits of drugs used in
      chemotherapy are carefully considered such that the benefits of using a new drug
      outweigh the risks in terms of the side effects caused by the drug. Damage to
      normal cells, tissues, organs and/or the whole organism is a big concern. Several
      tests are now routinely performed and are required for drug approval by various
      regulatory agencies around the globe. The primary goals of such preclinical
      safety evaluation of drugs are: (1) to identify an initial safe starting dose and
      subsequent dose escalation scheme to humans; (2) to identify potential target
      organs of toxicity and reversibility of toxicity; (3) to identify potential
      damage to the genetic material (genotoxicity); and (4) to identify parameters of
      clinical monitoring. In this paper, various models for genotoxicity assays are
      presented. These include: Ames assay, in vitro chromosome aberration assay and an
      in vivo micronucleus assay. New technologies, such as DNA adduct formation, DNA
      strand breakage, apoptotic changes, p53 gene expression and transgenic animal
      models, are also considered.

PMID- 9587397
TI  - cis-Active elements of Friend spleen focus-forming virus: from disease induction
      to disease prevention.
AB  - The polycythemic strain of the Friend spleen focus-forming virus (SFFVp) is a
      replication-defective, acutely transforming retrovirus inducing a bistage
      erythroleukemia in susceptible mice. The first stage of the disease is an acute
      polyclonal erythroblastosis induced by the proliferation-promoting effect of
      gp55. gp55 is expressed from a spliced subgenomic message of SFFVp and stimulates
      the cellular receptor for erythropoietin. Using a selectable SFFVp that otherwise
      mimics the specificity of the disease, we demonstrate that the kinetics of the
      polyclonal expansion depends on the transcriptional strength of the retroviral
      cis-active elements. By exchanging gp55 for apathogenic genes, we show that SFFVp
      enhancer and splice signals can be successfully utilized for the development of
      retroviral vectors mediating very efficient transgene expression in hematopoietic
      cells. Apathogenic selectable SFFVp-based vectors carrying distinct enhancer
      alterations are a valuable tool to analyze transcriptional control of leukemia
      viruses in the absence of oncogenic proteins. Moreover they might have
      therapeutic potential.

PMID- 9587396
TI  - Lack of functional Pit-1 and Pit-2 expression on hematopoietic stem cell lines.
AB  - Hematopoietic stem cells (HSC) are an important target for retroviral gene
      transfer. However, transduction efficiency in these HSC is extremely low compared
      to fibroblasts or more mature hematopoietic cells. This infection block was
      analyzed in the HSC line FDC-Pmix. The infection frequency with the amphotropic
      murine leukemia virus (MLV-A) is more than 100-fold lower in FDC-Pmix cells as
      compared to fibroblasts. Pseudotyping with the env of the 10A1 strain (MLV-10A1),
      which uses both the amphotropic receptor (Pit-2) and the receptor for gibbon ape
      leukemia virus (Pit-1), did not improve the infection efficiency. Vectors
      pseudotyped with VSV G protein were found to overcome the infection block in FDC
      Pmix, confirming that the block is at the level of virus binding and possibly
      penetration. Accordingly, we could not detect virus binding of MLV-A or MLV-10A1
      to FDC-Pmix cell lines. Northern blot analysis was performed to detect whether
      the defect is at the level of transcription. Surprisingly, similar levels of Pit
      2 receptor transcripts were detected in all cell types. The overexpression of rat
      Pit-2 DNA in CHO but not in FDC-Pmix cells improved amphotropic infection
      frequency after introducing rat Pit-2 DNA into the cells. Taken together these
      results show that the inefficient infection of FDC-Pmix is due to a lack of
      functional receptors. Either the receptor protein is incorrectly processed in
      these cells or a cofactor is missing in FDC-Pmix cells that is necessary for
      efficient binding and/or penetration.

PMID- 9587398
TI  - Role of IL-10 in the crossregulation of prostaglandins and cytokines in
      monocytes.
AB  - In the present study we have focused mainly on the role of IL (interleukin)-10 in
      the crossregulation of prostaglandins and cytokines in human monocytes. We first
      determined the effects of tumor necrosis factor-alpha (TNF-alpha) and IL-10 on
      monocyte prostaglandin E2 (PGE2) production. Unstimulated monocytes
      constitutively produced a small but significant amount of PGE2 in the culture
      supernatants. Both TNF-alpha and lipopolysaccharide (LPS) caused a remarkable
      increase in monocyte PGE2 production. On the other hand, IL-10 alone was without
      effect on constitutive PGE2 production but drastically inhibited LPS-induced PGE2
      production in monocytes. Moreover, this inhibitory effect of IL-10 was not simply
      attributable to its inhibition of TNF-alpha production in LPS-stimulated
      monocytes. Next, we determined the effect of PGE2 on TNF-alpha mRNA expression in
      monocytes. Treatment of monocytes with or without PGE2 showed no detectable TNF
      alpha mRNA. Activation of monocytes by LPS resulted in a remarkable accumulation
      of TNF-alpha mRNA and PGE2 efficiently inhibited this expression. Finally, we
      determined the effect of PGE2 on IL-10 mRNA expression in monocytes. Similar to
      TNF-alpha mRNA, unstimulated monocytes showed no detectable IL-10 mRNA.
      Interestingly, PGE2 alone drastically induced IL-10 mRNA. Besides, activation of
      monocytes by LPS resulted in a remarkable accumulation of IL-10 mRNA, and PGE2
      further enhanced this expression. These results indicate that TNF-alpha and PGE2
      are key molecules for the induction of IL-10 in monocytes, and that IL-10, in
      turn, plays a crucial role in terminating the inflammatory cascade via
      downregulation of production of proinflammatory molecules including TNF-alpha and
      PGE2.

PMID- 9587399
TI  - Immune response and neurotrophic factor interactions in peripheral nerve
      transplants.
AB  - Several types of immunocompetent cells of hematopoietic origin are involved in
      determining the immunological and regenerative fate of peripheral nerve
      transplants used for neurosurgical repair. The present study compares the
      immunological fate of nerve isografts and allografts with emphasis on the
      immunobiological events and neurotrophic interactions leading to graft survival
      and nerve fiber regeneration through them. The nerve transplantation model is
      unique as tissue rejection/inflammation is observed along with the nerve
      regeneration process. Nerve grafts become vascularized within a few days via
      neovascularization after transplantation. This is followed by progressive
      invasion of host macrophages and T lymphocytes that recognize the histocompatible
      antigens and initiate the rejection response. Two main types of donor resident
      cells are involved in early stages of graft rejection. These are macrophages and
      Schwann cells. Both of these cells have been found to possess antigen-presenting
      function and also can produce several cytokines. The most relevant to the
      peripheral nerves are tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1),
      interferon-gamma (IFN-gamma) and IL-12. TNF-alpha in addition to its capacity to
      kill cells is involved in activation of macrophages. IL-12 and IFN-gamma have a
      potential role in modulating and enhancing of the immune response. Finally, IL-1
      is of special significance because it promotes the expression of nerve growth
      factor (NGF) by the Schwann cells of the peripheral nerve and is important for
      nerve fiber regeneration. NGF in turn has been shown to enhance macrophage
      function and inflammatory response. Taken together, these findings show that NGF
      levels and inflammation in injured tissue play an important role in determining
      the success of transplants and in tissue repair.

PMID- 9587400
TI  - Role of cytokines in healing chronic skin wounds.
AB  - In the chronic wound, the normal cascade of inflammation, granulation and
      reconstruction phases of healing is interrupted. Cytokines are now known to
      orchestrate different biochemical mediators resulting in the restoration of the
      healing phases. Growth factors may play a significant role in stimulating wound
      repair by stimulating growth and proliferation. Since growth factors stimulate a
      variety of functions depending on cell type and wound stage and since wound
      healing defects may occur at any phase of healing, a mixed combination of growth
      factors would be predicted to be more effective than a single factor. Factors
      that may modulate the action of growth factors include electrical stimulation,
      weight bearing, debriding and ischemia.

PMID- 9587401
TI  - Regulation of both erythroid and megakaryocytic differentiation of a human
      leukemia cell line, UT-7.
AB  - UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on
      interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or
      erythropoietin (EPO) for growth and survival. Among its sublines, UT-7/GM, which
      remains undifferentiated in the presence of GM-CSF, has a bipotency showing
      differentiation into erythroid or megakaryocytic cell lineages in the presence of
      EPO or thrombopoietin (TPO), respectively. To investigate the mechanism
      underlying determination of cell differentiation, we investigated the role of
      signal transducers and activators of transcription (STAT) in EPO-induced
      erythroid differentiation. UT-7 cells grow in response to GM-CSF and EPO but do
      not differentiate into mature cells. UT-7/GM cells grow in response to GM-CSF and
      differentiate into erythroid cells by EPO. In UT-7 cells, both GM-CSF and EPO
      induced the activation of Stat1 alpha, Stat3 and Stat5. In UT-7/GM cells, EPO
      activated Stat5 alone, although the activation of Stat1 alpha, Stat3, and Stat5
      was induced by GM-CSF or TPO. In addition, GM-CSF inhibited EPO-induced erythroid
      differentiation and concomitantly activated Stat1 alpha and Stat3 in UT-7/GM
      cells even in the presence of EPO. Further we transfected Stat1 alpha, Stat3 cDNA
      or both into UT-7/GM cells. Hemoglobin-positive cells were decreased in the
      stable transfectants stimulated with EPO. These results indicate that Stat1 alpha
      and Stat3 have an inhibitory effect on the EPO-induced erythroid differentiation,
      and more complicated combination of transcription factors may play an important
      role in the decision of cell differentiation.

PMID- 9587402
TI  - Capacity of 1,25-dihydroxyvitamin D to stimulate expression of calbindin D
      changes with age in the rat.
AB  - Studies in rats and humans have shown that there is an age-related decline in the
      stimulation of intestinal Ca transport by 1,25-dihydroxyvitamin D3 [1,25(OH)2D],
      the active metabolite of vitamin D. The calbindins are a family of vitamin D
      dependent calcium-binding proteins found in the intestine (calbindin D-9k) and
      kidney (calbindin D-28k) and are thought to play a role in calcium transport and
      homeostasis. The purpose of this study was to determine if the capacity of
      1,25(OH)2D to stimulate the expression of calbindin protein and mRNA changes with
      age. Young (2 months), adult (12 months), and old (22 months) male F344 rats were
      made deficient in 1,25(OH)2D by being fed a strontium-containing diet and then
      being given a single i.p. injection of 1,25(OH)2D. Calbindin protein levels were
      measured by immunological techniques using specific antisera, and mRNA levels
      were measured by Northern and dot blots. The maximal amount of calbindin D-9k
      protein induced by 1,25(OH)2D declined with age in the duodenum but not in the
      ileum. In time-course studies, there was a delay in calbindin D-9k induction in
      the duodenum but not in the ileum of adult rats compared to young rats. In
      contrast to protein induction, maximal calbindin D-9k mRNA levels in response to
      1,25(OH)2D were greater in the adult animal and showed no time lag compared to
      those in the young animal. In the kidney, maximal levels of renal calbindin D-28k
      protein and mRNA did not change with age, but there was delayed induction in the
      adult. These studies demonstrate that there is an age-related decrease in the
      induction of calbindin protein in response to 1,25(OH)2D in the duodenum, but not
      in the ileum or kidney. This decline may be due to decreased translation of
      calbindin D-9k mRNA into protein in the duodenum with age.

PMID- 9587403
TI  - Bilirubin is an effective antioxidant of peroxynitrite-mediated protein oxidation
      in human blood plasma.
AB  - Bilirubin is a bile pigment that may have an important role as an antioxidant.
      Its antioxidant potential is attributed mainly to the scavenging of peroxyl
      radicals. We investigated the reaction of bilirubin with peroxynitrite in
      phosphate buffer and in blood plasma. In phosphate buffer bilirubin was rapidly
      oxidized by micromolar concentrations of peroxynitrite, and its oxidation yield
      was higher at alkaline pH with an apparent pKa = 6.9. In contrast, the major
      oxidation product of bilirubin in plasma was biliverdin, and the pH profile of
      its oxidation yield showed a slightly increased oxidation at acidic pH without a
      clear inflection point. The addition of NaHCO3 to bilirubin decreased the
      peroxynitrite-dependent oxidation, suggesting that the reactive intermediates
      formed in the reaction between CO2 and peroxynitrite are less efficient oxidants
      of bilirubin. The antioxidant role of bilirubin was investigated in some
      peroxynitrite-mediated plasma protein modifications that are enhanced by CO2
      (tryptophan oxidation and protein tyrosine nitration) or slightly decreased by
      CO2 (protein carbonyl groups). Bilirubin in the micromolar concentration range
      afforded a significant protection against all these oxidative modifications and,
      notably, protected plasma proteins even when the pigment was added 5 s after
      peroxynitrite (i.e., when peroxynitrite is completely decomposed). The loss of
      tryptophan fluorescence triggered by peroxynitrite was a relatively slow process
      fulfilled only after a few minutes. After this time, bilirubin was unable to
      reduce the tryptophan loss, and it was unable to reduce previously formed
      nitrated albumin or previously formed carbonyls. We deduce that bilirubin in
      plasma cannot react to a significant extent with peroxynitrite, and we suggest
      that bilirubin, through a hydrogen donation mechanism, participates as a
      scavenger of secondary oxidants formed in the oxidative process.

PMID- 9587404
TI  - One of the fumarate reductase isoenzymes from Saccharomyces cerevisiae is encoded
      by the OSM1 gene.
AB  - Soluble fumarate reductase from yeast irreversibly catalyzes the reduction of
      fumarate to succinate and has noncovalently bound flavin adenine dinucleotide. In
      yeast, there are two isoenzymes of fumarate reductase, which can be distinguished
      on the basis of their absorption or nonabsorption to DE-52 columns. Previously,
      we have purified FRDS1 and isolated its gene (FRDS) from Saccharomyces
      cerevisiae. In the present study, FRDS2 was purified to homogeneity by four
      chromatography steps. The N-terminal and C-terminal amino acid sequences of FRDS2
      were identical to the deduced amino acid sequence of the OSM1 gene (EMBL Database
      Accession No. L-26347), whose isolation and biochemical properties have not been
      studied up until now. From these results, we conclude that FRDS2 is encoded by
      the OSM1 gene. The deduced amino acid sequence of the OSM1 gene revealed that
      FRDS2 is synthesized as a precursor protein containing a presequence composed of
      32 amino acid residues. The mature enzyme consists of a protein of 469 amino acid
      residues with a molecular weight of 51,370. The N-terminal extension had the
      characteristics of a typical signal sequence required for targeting and sorting
      to a noncytosolic destination. In fact, FRDS2 was found to be located in
      promitochondria.

PMID- 9587405
TI  - Functional consequences of mutations in Ser-52 and Ser-60 in human blood
      coagulation factor VII.
AB  - Human blood coagulation factor VII has unique carbohydrate moieties O
      glycosidically linked to serine 52 and serine 60 residues in its first epidermal
      growth factor-like domain. To study the functional role of these glycosyl
      moieties in factor VII, we constructed, expressed, and purified site-specific
      recombinant mutants of human factor VII in which serine 52 and serine 60 were
      conservatively replaced with alanine residues. S52A factor VIIa (Ser-52-->Ala),
      S60A factor VIIa (Ser-60-->Ala), and S52,60A factor VIIa (Ser-52, Ser-60-->Ala)
      exhibited 56, 73, and 44%, respectively, of the clotting activity of wild-type
      factor VIIa using human brain thromboplastin as a source of tissue
      factor/phospholipids and 32, 43, and 14% of wild-type factor VIIa using a mixture
      of recombinant soluble tissue factor and mixed brain phospholipids. The tissue
      factor-dependent and -independent amidolytic activities of these mutants were
      essentially indistinguishable from that of wild-type factor VIIa. In addition,
      equilibrium dialysis experiments indicated that the profiles of 45Ca2+ binding to
      these mutants were identical with that of wild-type factor VII. In the presence
      of either Ca2+ or EGTA, the Kd values for the interaction of the three factor
      VIIa mutants to full-length tissue factor were 2- to 5-fold higher than that of
      wild-type factor VIIa, while the Kd values for the interaction of these mutants
      to soluble tissue factor were 4- to 15-fold higher than that of wild-type factor
      VIIa. Measurement of the association and dissociation rate constants for factor
      VIIa binding to relipidated tissue factor apoprotein revealed that the
      association rate constants of the three factor VII mutants were decreased in
      comparison with that of wild-type factor VIIa, while the dissociation rate
      constants of these three mutants were virtually identical to that of wild-type
      factor VIIa. These findings strongly suggest that glycosyl moieties attached to
      Ser-52 and Ser-60 in factor VII/VIIa provide unique structural elements that are
      important for the rapid association of factor VII/VIIa with its cellular receptor
      and cofactor.

PMID- 9587407
TI  - Production and characterization of two variants of human cystatin SA encoded by
      two alleles at the CST2 locus of the type 2 cystatin gene family.
AB  - Two variants of cystatin SA encoded by two alleles at the CST2 locus of the type
      2 human cystatin gene family were expressed in Escherichia coli. One, termed
      cystatin SA1, is identical to cystatin SA [S. Isemura, E. Saitoh, and K. Sanada
      J. Biochem. 102, 693-704, 1987]. Another, termed cystatin SA2, carries two amino
      acid substitutions (59Gly-->Asp; 120Glu-->Asp), one of which is in the so-called
      QXVXG region (the first hairpin loop) and another in the C-terminal portion of
      the molecule. Four recombinant cystatins [full-sized cystatin SA1, two N
      terminally truncated cystatin SA1 lacking four residues (WSPQ) and six residues
      (WSPQEE), and full-sized cystatin SA2] were purified from the periplasmic
      fractions of E. coli cells. Two N-terminally truncated recombinant cystatin SA1
      inhibited bovine cathepsin C with 2- to 20-fold lower Ki values than that of the
      full-sized one. In the inhibition of papain and ficin, however, both of the N
      terminally truncated cystatin SA1 displayed a 10-fold higher Ki value than that
      of full-sized one. In the inhibition of papain, ficin, and recombinant human
      cathepsin K, recombinant cystatin SA2 showed, respectively, 3826-, 1090-, and 30
      fold higher Ki values compared with those of SA1. Recombinant cystatin SA2
      inhibited bovine cathepsin C with a 50-fold lower Ki value compared with that of
      SA1. Recombinant cystatin SA1 did not inhibit human cathepsin H but SA2 inhibited
      it slightly (Ki = 528 nM). Neither of the recombinant variants inhibited bovine
      cathepsin B. Our data supply evidence indicating that the amino acid sequence of
      the first hairpin loop of the cystatin superfamily is important in the inhibition
      of papain, ficin, cathepsin C, cathepsin H, and cathepsin K.

PMID- 9587406
TI  - Dicyclohexylcarbodiimide inhibits proton pumping in ubiquinol:cytochrome c
      oxidoreductase of Rhodobacter sphaeroides and binds to aspartate-187 of
      cytochrome b.
AB  - In recent studies we reported that dicyclohexylcarbodiimide (DCCD) inhibited
      proton translocation in ubiquinol:cytochrome c oxidoreductase (cytochrome bc1
      complex) from yeast mitochondria where it was bound to aspartate-160 of
      cytochrome b. In the current study, we report that DCCD and its fluorescent
      analogue, N-cyclohexyl-N'-[4-(dimethylamino)naphthyl]-carbodiimide (NCD-4),
      inhibit 50-60% proton pumping in the cytochrome bc1 complex of the bacterium
      Rhodobacter sphaeroides with a 20% inhibition of electron transfer activity.
      Radioactive DCCD is bound exclusively to cytochrome b at aspartate-187, which is
      located at the C-terminal region of the CD loop connecting membrane-spanning
      helices C and D of cytochrome b. Fluorescent studies with NCD-4 revealed that
      aspartate-187 is located in a mildly hydrophobic pocket in the bc1 complex at a
      distance of 2-3 A from the surface of the membrane.

PMID- 9587408
TI  - The role of N-glycosylation of human thromboxane A2 receptor in ligand binding.
AB  - Thromboxane A2 receptor (TXA2R) was expressed in insect Sf21 cells and
      demonstrated to interact with 8-iso-PGF2 alpha and 9 alpha, 11 beta-PGF2 alpha
      with a potency similar to that of TXA2 agonist U46619. TXA2R was shown to be a
      glycoprotein. The role of N-glycosylation of TXA2R in ligand binding was
      investigated in the insect cells over-expressed with recombinant TXA2R. Deletion
      of the carbohydrate moiety by adding tunicamycin during infection of Sf21 cells
      or mutation of both potential N-glycosylation sites (Asn-4 and Asn-16) abolished
      the ligand binding of TXA2R, suggesting that N-glycosylation is crucial for
      binding function. Mutation of either Asn-4 or Asn-16 to a leucine did not have
      much effect on maximal binding. However, the mutant receptors possess lower
      binding affinity toward TXA2R antagonist [3H]SQ29548. Furthermore, the binding
      specificity of the mutant receptors was shown to be altered. Our data suggest
      that both Asn-4 and Asn-16 are glycosylated and glycosylation on either site is
      sufficient for ligand recognition. However, glycosylation on both sites is
      required to maintain binding affinity and specificity.

PMID- 9587409
TI  - Imidazole binding to horse metmyoglobin: dependence upon pH and ionic strength.
AB  - The reaction between metmyoglobin and imidazole has been studied as a function of
      pH between pH 4.2 and 11.5 and as a function of ionic strength at integral pH
      values (5 to 10) between 0.001 and 1.0 M ionic strength. The reaction between
      metmyoglobin and 1-methylimidazole has also been investigated as a function of
      pH. Comparison of the pH dependence of the association rate constants for the two
      ligands indicates that the negatively charged imidazolate ion does not contribute
      to the observed rate of imidazole binding at pH < or = 11.5. At all pH values
      between pH 4.2 and pH 11.5 the initial complex formed involves the neutral form
      of bound imidazole. At pH 11.5, the neutral imidazole complex is converted slowly
      (t1/2 approximately 10 s) into an imidazolate complex. The kinetic data were
      analyzed according to two mechanisms, one involving the binding of neutral
      imidazole only and one involving the direct binding of both imidazole and the
      imidazolium ion to metmyoglobin. Although secondary kinetic salt effects account
      for the ionic strength dependence of the association rate constant, evidence
      which indicates that metmyoglobin reacts with imidazole and with the imidazolium
      ion with similar rates is provided. A self-consistent analysis indicates that the
      rate constants for imidazole and imidazolium ion binding to metmyoglobin are 350
      and 230 M-1 s-1, respectively, at neutral pH and 0.1 M ionic strength. Imidazole
      can react directly with hydroxymetmyoglobin with a rate of 56 M-1 s-1 at 0.1 M
      ionic strength, about sixfold slower than binding to aquometmyoglobin.
      Protonation of a second heme-linked group, thought to be His-97, has little
      influence on the binding of imidazole but does decrease the rate of imidazolium
      binding by about eightfold to 29 M-1 s-1 at 0.1 M ionic strength.

PMID- 9587410
TI  - Electron transport-linked ubiquinone-dependent recycling of alpha-tocopherol
      inhibits autooxidation of mitochondrial membranes.
AB  - The objective of this study was to elucidate the anti-oxidative roles of coenzyme
      Q (CoQ) and alpha-tocopherol in mitochondrial membranes by determining whether
      CoQ directly scavenges peroxyl- and alkoxyl-radicals or indirectly regenerates
      alpha-tocopherol during autooxidation of mitochondrial membranes. A comparison of
      the interaction between alpha-tocopherol and CoQ during autooxidation was made
      between bovine and rat heart mitochondria, which differ approximately 15-fold in
      their alpha-tocopherol content. Autooxidation of both bovine and rat heart
      mitochondria resulted in the formation of thiobarbituric-acid-reactive substances
      and protein carbonyls; however, the differences in the autooxidizability of
      mitochondria between rat and bovine heart mitochondrial membranes were relatively
      minor. Supplementation of rat heart mitochondria with succinate caused reduction
      of CoQ to ubiquinol while alpha-tocopherol concentration remained unaffected
      during autooxidation. In contrast, in the absence of succinate, CoQ was present
      in the oxidized form (ubiquinone) and the mitochondrial membranes were depleted
      of alpha-tocopherol. CoQ concentrations remained unchanged over time irrespective
      of the presence or absence of succinate. In the absence of succinate,
      autooxidation of bovine SMPs, supplemented with different amounts of alpha
      tocopherol, was inversely related to the amount of alpha-tocopherol, whereas in
      the presence of succinate autooxidation was greatly reduced. Results of this
      study indicate that during autooxidation of mitochondria, alpha-tocopherol acts
      as the direct radical scavenger, whereas ubiquinol regenerates alpha-tocopherol.

PMID- 9587411
TI  - The familial amyotrophic lateral sclerosis-associated amino acid substitutions
      E100G, G93A, and G93R do not influence the rate of inactivation of copper- and
      zinc-containing superoxide dismutase by H2O2.
AB  - Inactivation of copper- and zinc-containing superoxide dismutase (Cu,ZnSOD) by
      H2O2 is the consequence of several sequential reactions: reduction of the active
      site Cu(II) to Cu(I) by H2O2; oxidation of the Cu(I) by a second H2O2, thus
      generating a powerful oxidant, which may be Cu(I)O or Cu(II)OH or Cu(III); and
      finally oxidation of one of the histidines in the ligand field, causing loss of
      SOD activity. Three familial amyotrophic lateral sclerosis (FALS)-associated
      mutant Cu,ZnSODs, i.e., E100G, G93A, and G93R, did not differ from the control
      enzyme in susceptibility to inactivation by H2O2. It thus appears that an
      increased peroxidase activity of the FALS-associated Cu,ZnSOD variants might not
      be a factor in the development of this disease. This leaves the loss of Zn, and
      the consequent increase in peroxidase activity, or in nitration activity, as a
      viable explanation (J. P. Crow et al., 1997, J. Neurochem. 69, 1936-1944), among
      other possibilities.

PMID- 9587412
TI  - Changes in the hepatic mitochondrial respiratory system in the transition from
      weaning to adulthood in rats.
AB  - In the present study we investigated the changes in the hepatic mitochondrial
      respiratory system in the transition from weaning to adulthood in the rat. We
      conceptually divided the system into blocks of reactions that produced or
      consumed mitochondrial membrane potential and then measured the kinetic responses
      of these blocks of reactions to changes in this potential in isolated liver
      mitochondria from 25- and 60-day-old rats using succinate as substrate. Moreover,
      we considered the mitochondrial membrane potential producers to be divided into
      blocks of reactions that reduced or oxidized ubiquinone-2 (Q-2) and then measured
      the kinetic responses of these two blocks to changes in Q-2 redox state as well
      as the flux control coefficients and the cytochrome content. We found that adult
      rats exhibited significantly higher state 3 respiratory rates with increased
      kinetic response of the substrate oxidation pathway to the mitochondrial membrane
      potential, slightly decreased activity of the phosphorylating system, increased
      kinetic responses of both Q-2 reducers and oxidizers to Q-2 redox state, and
      increased cytochrome content. Our results indicate that important changes in the
      hepatic mitochondrial respiratory system occur in the transition from weaning to
      adulthood in rats.

PMID- 9587413
TI  - A kinetic study of site-directed mutants of Escherichia coli ADP-glucose
      pyrophosphorylase: the role of residue 295 in allosteric regulation.
AB  - The effects of amino acid substitutions at residue 295 on the regulatory
      properties of Escherichia coli ADP-glucose pyrophosphorylase were studied. In
      previous studies, this residue, altered from proline to serine (P295S) in the
      gene of a mutant strain of E. coli, resulted in a high-activity form of enzyme
      [higher activity in absence of activator fructose 1,6-bisphosphate (FBP), higher
      apparent affinity for FBP and substrates, and lower apparent affinity for the
      inhibitor, AMP]. The effects of size and charge on this site were explored by
      replacing Pro with Gly, Asp, Asn, Gln, or Glu. All mutant enzymes were expressed
      and purified for kinetic analysis. All mutant enzymes, to varying extents, were
      in more active form than the wild-type enzyme. Enzymes with a substituted
      negative charge (P295D, P295E) had the highest activity in the absence of FBP,
      while the P295G enzyme was most similar to the wild type. The P295D and P295E
      enzymes had the lowest apparent affinities for AMP; this effect was partially
      abolished by the neutral substitutions P295N and P295Q. Another mutation, G336D,
      had previously been found to produce an even higher activity enzyme form. In
      order to examine interactions between substitutions at the 295 and 336 positions,
      the double mutant P295D-G336D was constructed and characterized. The double
      mutant enzyme was more active in the absence of FBP, with a higher affinity for
      FBP and a lower apparent affinity for AMP than either single mutated enzyme. The
      significance of residue 295 in regulation is discussed.

PMID- 9587414
TI  - Differential regulation of extracellular signal-regulated kinase and nuclear
      factor-kappa B signal transduction pathways by hydrogen peroxide and tumor
      necrosis factor.
AB  - Reactive oxygen metabolites are increasingly recognized for their ability to
      stimulate signal transduction pathways. This is important because these oxidants
      are frequently generated at sites of inflammation. However, little is known about
      the manner in which reactive oxygen species may selectively stimulate distinct
      signaling pathways. We have examined this question by stimulating mesothelial
      cells with hydrogen peroxide (H2O2) as a model oxidant stimulus. The response to
      H2O2 was examined by measuring the activation of the extracellular signal
      regulated kinase (ERK1/2) and the nuclear factor-kappa B (NF-kappa B) signal
      transduction pathways. We found that H2O2 stimulated activity of the ERK1/2
      pathway in a dose- and time-dependent manner. The ability of H2O2 to activate
      ERK1/2 was similar to that found with tumor necrosis factor (TNF) stimulation.
      The oxidant effect was inhibited by various reactive oxygen scavengers. An
      inhibitor of mitogen-activated protein kinase/extracellular signal-regulated
      kinase, the upstream kinase that activates ERK1/2, inhibited the oxidant effect.
      The superoxide anion (O2-) also stimulated ERK1/2 activity. In contrast, H2O2 did
      not stimulate proteolysis of I kappa B-alpha and induced only a small degree of
      NF-kappa B nuclear translocation. Stimulation of the cells with O2- also induced
      a minimal degree of NF-kappa B activation. TNF was a potent stimulus for I kappa
      B-alpha proteolysis and NF-kappa B activation, demonstrating that the cells did
      have a functional NF-kappa B pathway. These results suggest that oxidants may
      selectively stimulate certain pathways, thereby preserving some specificity of
      the signaling process. Furthermore, different cell types and distinct signaling
      pathways within cells may demonstrate unique profiles in the manner in which they
      respond to oxidant stimulation.

PMID- 9587415
TI  - Expression of pyruvate dehydrogenase isoforms during the aerobic/anaerobic
      transition in the development of the parasitic nematode Ascaris suum: altered
      stoichiometry of phosphorylation/inactivation.
AB  - The pyruvate dehydrogenase complex (PDC) plays a key role in the anaerobic
      metabolism of the parasitic nematode Ascaris suum. Two isoforms of the alpha
      subunit of pyruvate dehydrogenase (E1) have been identified: alpha I is most
      abundant in anaerobic adult muscle and alpha II in aerobic larvae. Both isoforms
      have been expressed as alpha 2 beta 2 tetramers with a muscle-specific beta
      subunit, purified to apparent homogeneity, reconstituted with E1-deficient adult
      A. suum muscle PDC, and assayed for PDC and E1 kinase activity. Recombinant alpha
      II is a poor substrate for the adult E1 kinase, but its stoichiometry of
      phosphorylation/inactivation is similar to that reported for the human E1.
      Initially, inactivation parallels the incorporation of about 1 mol 32P/mol E1 and
      at maximal phosphorylation about 2.4 32P/mol E1 is incorporated. In contrast,
      recombinant alpha I (r alpha I) is phosphorylated rapidly, and substantially more
      phosphorylation accompanies inactivation. To examine this altered pattern of
      phosphorylation, the two phosphorylation sites in each E1 alpha subunit of the r
      alpha I (site 1 and site 2) were changed either individually or together from Ser
      to Ala by site-directed mutagenesis. Site 1 was phosphorylated more rapidly than
      site 2, but the phosphorylation of either site resulted in inactivation, and the
      phosphorylation of only a single E1 alpha subunit of the tetramer was necessary
      for inactivation. However, both E1 alpha subunits of the tetramer were
      phosphorylated, based on the incorporation of about 3.5 mol 32P/mol E1 at maximal
      phosphorylation and the altered mobility of most of the E1 alpha subunits during
      SDS-PAGE. These observations suggest that the regulation of both E1 isoforms is
      modified to maintain PDC activity during the transition to anaerobiosis.

PMID- 9587416
TI  - CYP2M1: cloning, sequencing, and expression of a new cytochrome P450 from rainbow
      trout liver with fatty acid (omega-6)-hydroxylation activity.
AB  - A cDNA clone was isolated from a female rainbow trout liver lambda g tau 11
      library using polyclonal antibodies raised against rainbow trout cytochrome P450
      LMC1. This 2149-nucleotide clone contained an open reading frame encoding a
      protein of 499 amino acids with a calculated M(r) of 56,850 Da. On the basis of
      cytochrome P450 (P450) amino acid sequence comparisons, this rainbow trout P450
      was assigned by the P450 Nomenclature Committee to a new P450 subfamily
      designated as CYP2M1. Northern blot results suggest that the expression of CYP2M1
      at the transcriptional level was generally sex, tissue, and age specific. By use
      of a full-length CYP2M1 cDNA probe, it was observed that this cDNA hybridized
      strongly to a single 2.2-kb transcript in juvenile female rainbow trout trunk
      kidney and in liver from juvenile and sexually mature trout from both sexes.
      Negligible amounts of mRNA hybridizable to CYP2M1 cDNA were found in the juvenile
      and sexually mature male trunk kidney. cDNA-directed expression in COS-7 cells
      and of recombinant baculovirus in insect cells produced a protein that was
      reactive with rabbit anti-trout P450 LMC1 polyclonal antibody and exhibited the
      unique (omega-6)-hydroxylation toward lauric acid previously observed with
      rainbow trout P450 LMC1.

PMID- 9587417
TI  - Radiation effects on the native structure of proteins: fragmentation without
      dissociation.
AB  - Several proteins (avidin, carboxypeptidase B, glucose-6-phosphate dehydrogenase,
      glutamate dehydrogenase, maltase, and peroxidase) composed of one to six subunits
      were irradiated in the frozen state. Each irradiated protein was examined by size
      exclusion chromatography (SEC) and by denaturing gel electrophoresis (SDS-PAGE).
      All these proteins eluted from SEC as a single peak even though SDS-PAGE showed
      cleavage of the polypeptide backbone of the monomers. Thus, fragmentation of the
      subunits did not result in dissociation of the oligomeric structure.

PMID- 9587418
TI  - Kinetics of enzymes with isomechanisms: britton induced transport catalyzed by
      bovine carbonic anhydrase II, measured by rapid-flow mass spectrometry.
AB  - Induced transport of 13CO2 to H13CO3- by bovine carbonic anhydrase II in the
      presence of excess H12CO3- at pH 6.35 causes a temporary decrease in the
      concentration of 13CO2 from 0.169 to 0.092 +/- 0.003 mM, measured in less than
      half a second with a new rapid-flow, membrane-inlet mass spectrometer. From this
      perturbation, a value of 83 +/- 0.3 M-1 is calculated for the alpha term in Eq.
      [26] of H. G. Britton (Biochem. J. 133, 255-261, 1973). Combining alpha with the
      K(m) for bicarbonate (32 +/- 1 mM) and Eqs. [7] and [21] of K. L. Rebholz and D.
      B. Northrop (Methods Enzymol, 249, 211-240, 1995) yields a ratio of less than
      0.57 +/- 0.04 for the apparent rate constants representing the isomerization
      segment and chemical conversion segment, respectively, of the enzyme-catalyzed
      dehydration of bicarbonate. These results provide proof positive for the
      previously inferred (but unproven despite universal acceptance) isomechanism for
      the carbonic anhydrases. Moreover, the data and new equations quantify the
      proposed internal proton transfer to be 64 +/- 4% rate-limiting for the bovine
      type II isoenzyme, a value similar to but more precise than estimates based upon
      solvent isotope effects and product inhibition kinetics.

PMID- 9587419
TI  - Oxidative DNA damage in mouse heart, liver, and lung tissue due to acute side
      stream tobacco smoke exposure.
AB  - Environmental tobacco smoke (ETS) is a hotly debated social, political, and
      scientific issue, pitting smokers' rights against the health and safety of
      nonsmokers. Striking an acceptable balance between the two depends largely on the
      potential health hazard assessment of ETS. Studies from this laboratory have
      shown that exposure to side-stream cigarette smoke (SSS), the major component of
      ETS, significantly increases oxidative stress in mouse heart, liver, and lung
      tissues. This study measures the level of oxidative damage to mouse liver, lung,
      and heart DNA as a result of this oxidative stress. Adult female Balb/c mice were
      exposed to a regimen consisting of sequences of a 30-min exposure followed by a
      90-min nonexposure. This regimen was performed once for the single exposure and
      repeated three times for the triple exposure. The heart, lung, and liver were
      excised from the mice, and DNA was extracted and analyzed for the presence of the
      oxidative product 8-hydroxy-2'-deoxyguanosine (8-OHdG). In all three tissues, the
      exposure increased the presence of 8-OHdG above the control levels. In some
      instances, the increased levels returned to normal by the end of the nonexposure
      period, while other tissues showed a further increase following nonexposure.
      These studies demonstrate that limited exposure to SSS produces measurable DNA
      oxidative damage.

PMID- 9587420
TI  - AP-1 activity affects the levels of induced erythroid and megakaryocytic
      differentiation of K562 cells.
AB  - The effect of modulating AP-1 activity on the levels of induced erythroid and
      megakaryocytic differentiation of the erythroleukemia cell line K562 was
      examined. Cells were stably transfected with expression vectors encoding either a
      tetracycline-responsive dominant negative c-Jun (JunDN) or a hybrid Raf protein
      inducible by estrogen. Down-regulation of AP-1 activity by induction of JunDN
      enhanced erythroid differentiation by two agents, cytosine arabinoside and
      activin A. Induction of AP-1 activity by elevated Raf activity inhibited
      erythroid differentiation, thus mimicking the well-known effect of tetradecanoyl
      phorbol acetate (TPA) on this process. Induced Raf activity also brought about
      partial megakaryocytic differentiation of the line. However, inhibition of TPA
      induced AP-1 activity by induction of JunDN gave mixed results. While the
      cytological effects of TPA treatment observed on cytochemical staining were
      inhibited by JunDN, two protein markers for megakaryocytic differentiation were
      increased. These results, while supportive of current models of hematopoietic
      lineage-specific gene expression, suggest a complex and temporal mechanism of
      lineage commitment.

PMID- 9587421
TI  - Identification of a novel human glutathione S-transferase using bioinformatics.
AB  - In searching the expressed sequence tag (EST) data-base of GenBank with coding
      sequences of 11 known human glutathione S-transferases in conjunction with
      bioinformatic analysis, we have identified five ESTs that encode a new human
      glutathione S-transferase (GST) designated GST A4. The cDNA clone (I.M.A.G.E.
      Consortium cDNA Clone ID 515157) had an insert length of 1279 bp and contains an
      open reading frame of 666 bp, which encodes a protein of 222 amino acid residues.
      The GST A4 protein is identical in length to human GST A1 and A2 and is 54%
      identical to human GST A1 and A2. Sequence comparison with other human GSTs
      suggests that it is a new GST belonging to the alpha class GSTs. Northern blot
      analysis and EST database searches have demonstrated that the GST A4 mRNA is
      expressed at a high level in brain, placenta, and skeletal muscle and much lower
      in lung and liver. Analysis of the sequence tagged site (STS) database indicated
      that the GST A4 gene is located on chromosome 6. This STS represents a previously
      unidentified transcript further confirming the novelty of the new sequence.

PMID- 9587422
TI  - Tissue transglutaminase-catalyzed formation of high-molecular-weight aggregates
      in vitro is favored with long polyglutamine domains: a possible mechanism
      contributing to CAG-triplet diseases.
AB  - To investigate possible biochemical mechanisms underlying the "toxic gain of
      function" associated with polyglutamine expansions, the ability of guinea pig
      liver tissue transglutaminase to catalyze covalent attachments of various
      polyamines to polyglutamine peptides was examined. Of the polyamines tested,
      spermine is the most active substrate, followed by spermidine and putrescine.
      Formation of covalent cross links between polyglutamine peptides and polyamines
      yields high-M(r) aggregates--a process that is favored with longer
      polyglutamines. In the presence of tissue transglutaminase, purified
      glyceraldehyde-3-phosphate dehydrogenase (a key glycolytic enzyme that binds
      tightly to the polyglutamine domains of both huntingtin and dentatorubral
      pallidoluysian atrophy proteins) is covalently attached to polyglutamine peptides
      in vitro, resulting in the formation of high-M(r) aggregates. In addition,
      endogenous glyceraldehyde-3-phosphate dehydrogenase of a Balb-c 3T3 fibroblast
      cell line overexpressing human tissue transglutaminase forms cross-links with a
      Q60 polypeptide added to the cell homogenate. Possibly, expansion of
      polyglutamine domains (thus far known to occur in the gene products associated
      with at least seven neurodegenerative diseases) leads to increased/aberrant
      tissue transglutaminase-catalyzed cross-linking reactions with both polyamines
      and susceptible proteins, such as glyceraldehyde-3-phosphate dehydrogenase.
      Formation of cross-linked heteropolymers may lead to deposition of high-M(r)
      protein aggregates, thereby contributing to cell death.

PMID- 9587424
TI  - Aneuploidy: a report of an ECETOC task force.
AB  - Aneuploidy plays a significant role in adverse human health conditions including
      birth defects, pregnancy wastage and cancer. Although there is clear evidence of
      chemically induced aneuploidy in experimental systems, to date there are
      insufficient data to determine with certainty if chemically induced aneuploidy
      contributes to human disease. However, since there is no reason to assume that
      chemically induced aneuploidy will not occur in human beings, it is prudent to
      address the aneugenic potential of chemicals in the safety assessment process. A
      wide range of methods has been described for the detection of chemically induced
      aneuploidy including subcellular systems, tests with fungi, plants and Drosophila
      as well as in vitro mammalian systems and in vivo mammalian somatic and germ cell
      assays. However, none of these methods is sufficiently validated or widely used
      in routine screening. Underlying the efforts to develop aneuploidy-specific
      assays is the presumption that current genetic toxicology tests do not detected
      chemicals that have aneuploidy-inducing potential. To address this, we have
      critically evaluated data from standard genetic toxicology assays for 16 known or
      suspected aneugens. The conclusions from the review are listed below. 1. At
      present there are only nine chemicals that can be classified as definitive
      aneugens, as determined by positive results in in vivo rodent assays. 2. As
      expected, the majority of definitive and suspected aneugens are negative in the
      bacterial mutation assay. 3. The majority of definitive aneugens evaluated induce
      polyploidy in vitro. With few exception, they also induced structural chromosome
      aberrations in vitro. 4. All of the definitive aneugens that have been
      sufficiently tested induce micronuclei in rodent bone marrow cells in vivo. A
      number of these chemicals also induced structural chromosome aberrations in vivo.
      5. There is no evidence for a unique germ cell aneugen, that is a chemical that
      induces aneuploidy in germ cells and not in somatic cells. Furthermore, an
      analysis of several databases indicates the proportion of chemicals which induce
      polyploidy and not chromosome aberrations in vitro is low. Based on these
      conclusions, the following recommendations are made: for screening purposes, a
      standard genotoxicity test battery (including an in vitro cytogenetic assay with
      an assessment of polyploidy and clastogenicity at the same harvest time) should
      be performed; in the absence of polyploidy induction in vitro no further
      evaluation of aneuploidy-inducing potential is needed; if polyploidy is observed,
      in vitro follow-up testing to investigate further the aneuploidy-inducing
      potential should be conducted; such follow-up testing will generally start with
      the conduct of a standard in vivo somatic cell micronucleus assay; if the in vivo
      somatic cell micronucleus assay is negative, with adequate evidence of exposure
      of the bone marrow to the test compound, no further testing of aneuploidy
      inducing potential is needed; if the in vivo somatic cell micronucleus assay is
      positive, further information on mechanisms of micronucleus induction can be
      obtained by using kinetochore/centromeric staining in vitro and/or in vivo; an
      assessment of potential germ cell aneuploidy activity may then be considered;
      aneuploidy induction which does not involve the direct interaction of a chemical
      or its metabolite(s) with DNA is expected to have a threshold. This must be
      considered in the risk assessment of such chemicals; this is not addressed by
      current risk assessment guidelines.

PMID- 9587425
TI  - Evaluation of the in vitro micronucleus test as an alternative to the in vitro
      chromosomal aberration assay: position of the GUM Working Group on the in vitro
      micronucleus test. Gesellschaft fur Umwelt-Mutations-forschung.
AB  - In order to license a pharmaceutical or chemical, a compound has to be tested for
      several genotoxicity endpoints, including the induction of chromosomal
      aberrations in vitro. A working group within the GUM has evaluated published data
      on the in vitro micronucleus test with the aim of judging its suitability as a
      replacement for the in vitro chromosomal aberration test. After strict rejection
      criteria were applied, a database including 96 publications and 34 compounds was
      obtained. For 30 of these compounds, data on both tests were available. For 24 of
      the 30, concordant results in both test systems were obtained (80% correlation).
      The discordant results in 6 compounds can be explained by a known or suspected
      aneugenic potential of these compounds. Considering that cell types and test
      protocols were extremely heterogeneous, this correlation is rather encouraging.
      Comparison of the different protocols, and experience established within the
      working group yielded several recommendations for the routine use of the in vitro
      micronucleus test. Although many cell lines are suitable, those most often used
      in genotoxicity testing (e.g. CHL, CHO, V79, human lymphocytes, L5178Y mouse
      lymphoma cells) are recommended. Cytochalasin B may be used in the case of human
      lymphocytes; however, the possibility of its interaction with aneugenic test
      compounds should be considered. For continuously dividing cell lines,
      cytochalasin B is not recommended by the working group. Although, there seems to
      be flexibility in the choice of treatment and sampling times, the average
      generation time of the chosen cell line of choice should be taken into account
      when determining sampling time, and treatment of cells for at least one cell
      cycle duration is recommended. The use of appropriate cytotoxicity tests is
      strongly recommended. Although studies on some parameters of the test protocol
      may be useful, the introduction of the in vitro micronucleus test into
      genotoxicity testing and guidelines should not be delayed. Even in its present
      state, the in vitro micronucleus is a reliable genotoxicity test. Compared with
      the chromosomal aberration test, it detects aneugens more reliably, it is faster
      and easier to perform, and it has more statistical power and the possibility of
      automation.

PMID- 9587426
TI  - Detecting chemical aneugens: a commentary to 'Aneuploidy: a report of an ECETOC
      task force'.

PMID- 9587427
TI  - [Management of myocardial infarction in patients over 75 years of age compared to
      patients under 75 years of age. Apropos of 594 consecutive cases admitted between
      1991 and 1994].
AB  - This study analyses the patients consecutively admitted for myocardial infarction
      between January 1991 and December 1994. The study population consisted of 594
      patients divided into two groups: 446 patients under the age of 75 years and 178
      patients over the age of 75 years. The sex-ratio showed a male predominance (84%)
      before 75 years, and a female predominance (57%) after 75 years. A history of
      angina was more frequent in elderly patients (45% vs 30%, p < 0.001), who were
      admitted later (22.5% vs 46.6% before the 6th hour, p < 0.001). Thrombolysis was
      administered in 49.6% of subjects under the age of 75 years and in 17.3% of
      elderly patients. The course was uneventful in 56.7% of subjects under the age of
      75 years and in 28.2% of elderly patients. Mortality was 6-fold higher in this
      group (22% vs 3.7%, p < 0.01). The cause of death was usually heart failure with
      a 10-fold higher frequency of cardiogenic shock (13.5% vs 1.4%, p < 0.001).
      Coronary angiography was performed in 81.4% of subjects under the age of 75 years
      and in 30% of the elderly patients. Multi-vessel lesions were more frequent in
      elderly subjects (78.4% vs 47.5%, p < 0.01). Revascularization by angioplasty or
      bypass graft was performed with a similar frequency (50%) in the two groups of
      patients investigated by coronary angiography. The mortality of myocardial
      infarction was high in the elderly, usually due to heart failure, and partly
      explained by the severity of the coronary lesions; in contrast, elderly patients
      were less frequently submitted to active management (thrombolysis-coronary
      angiography), while recent data of the literature argue in favour of primary
      angiography in these patients.

PMID- 9587428
TI  - [Prognostic value of serial electrophysiological tests in inducible sustained
      ventricular tachyarrhythmias].
AB  - The authors report the results of a study evaluating serial electrophysiological
      tests on a series of 166 patients with inducible sustained ventricular
      tachyarrhythmia. The initial electrophysiological investigation was indicated
      because of sustained ventricular arrhythmias documented in 95 patients or
      suspected in 71 symptomatic patients. Serial tests allowed identification of a
      protective antiarrhythmic treatment (non-inducible ventricular tachycardia) in 74
      responding patients (44.6%) (group R) after 1.3 +/- 0.5 therapeutic trials versus
      1.8 +/- 0.8 inconclusive trials in 92 non responding patients (group NR).
      Multivariate analysis demonstrated the absence of any underlying ischaemic heart
      disease (p < 0.01) and the presence of spontaneous ventricular fibrillation (p <
      0.01) as independent predictive factors of success during serial testing. A
      follow-up of 43 +/- 29 months was available for 151 patients (91%). kaplan-Meier
      survival curves showed a better long-term prognosis for group R with survival
      rates of 97%, 87% and 70% at 1.3 and 6 years, respectively, versus 83%, 68% and
      45% for group NR. Two variables were considered on multivariate analysis to be
      predictive factors of survival: left ventricular ejection fraction (p < 0.001)
      and response to serial electrophysiological tests (p < 0.02). Therapeutic
      ventricular pacing therefore remains a reliable method to select patients whose
      prognosis is improved with antiarrhythmic treatment after induction of sustained
      ventricular arrhythmia.

PMID- 9587429
TI  - [Electrocardiographic changes in chest deformities. Apropos of 20 cases in black
      subjects].
AB  - The objective of this study is to describe the electrocardiographic signs
      associated with certain chest deformities. This is a prospective, case-control
      study comparing 20 black subjects with chest deformity (11 cases of flat back
      syndrome, 5 cases of pigeon chest, 4 cases of funnel chest) with 20 age- and sex
      matched healthy controls. Cardiac duplex ultrasound was performed for each
      individual to exclude associated heart disease. Atypical electrocardiographic
      signs were observed in 15 subjects with chest deformity versus only 3 in the
      control group. The anomalies observed consisted of signs of atrial or ventricular
      hypetrophy, right branch block, abnormalities of repolarization on the T wave or
      ST segment. Chest deformities are therefore associated with several electrical
      signs simulating most cardiac diseases. A good knowledge of these modifications
      should help to avoid the numerous diagnostic traps associated with these signs.

PMID- 9587430
TI  - [New biological factors of thromboses].
AB  - Hypercoagulability states are caused by a disturbance of blood rheology due to
      the presence or pathological absence of a clotting factor. These abnormalities of
      haemostasis are essentially studied in the context of venous thrombosis. Over the
      years, in parallel with the progress in therapeutics, new laboratory
      abnormalities have been discovered and other, previously described, factors have
      been recently correlated with thrombotic phenomena. Based on a review of the
      literature, the authors describe the pathogenic role and the place of these
      various laboratory abnormalities in thromboembolic disease.

PMID- 9587431
TI  - [Isolated congenital diverticulum of the left ventricle disclosed by ventricular
      tachycardia in a 72-year-old woman].
AB  - A 72-year-old woman presented with poorly tolerated ventricular tachycardia
      reduced by intravenous amiodarone. The possibility of an ischaemic aetiology led
      us to perform coronary angiography. The coronary arteries were pathological. Left
      ventricular angiography revealed limited anterior hypokinesia and a large
      contractile apical pouch appended to the left ventricle by a long narrow neck.
      Despite the appearance suggestive of congenital left ventricular diverticulum
      (contractility, narrow neck) and because of the coexistence of ischaemic heart
      disease, we preferred to confirm the muscular nature of the diverticulum by
      myocardial thallium scintigraphy, which showed reversible decreased uptake in the
      anterior zone related to coronary artery disease, and confirmed the muscular
      nature of the diverticulum which showed normal thallium uptake. MRI clearly
      visualized the ventricular ectasia attached by a narrow neck to the rest the left
      ventricle. This long narrow neck indicated that this muscular diverticulum
      constituted a congenital diverticulum. The contribution of ultrasonography was
      limited by a poorly defined point during the examination. This congenital
      diverticulum, discover during adulthood, and previously asymptomatic, is a rare
      lesion, in the light of a review of the literature.

PMID- 9587432
TI  - [Cardiac lymphoma disclosed by tamponade and complete atrioventricular block:
      apropos of a surgically treated case. Heart and lymphoma].
AB  - Cardiac lymphoma is becoming increasingly frequent, especially in the context of
      acquired immune deficiency syndrome, and due to progress in imaging, particularly
      echocardiography. The authors report the case of a 49-year-old patient in whom
      the diagnosis of cardiac lymphoma was established in the presence of complete
      atrioventricular block, tamponade and right atrial tumour. The authors review the
      various electrocardiographic and echocardiographic features of cardiac lymphoma.

PMID- 9587433
TI  - [Coxiella burnetti infectious endocarditis. Apropos of a case].
AB  - Chronic forms of Q fever (endocarditis) are rare, but are responsible for severe
      and desperately recurrent infections, resulting in multiple valve replacements
      with a reserved prognosis. The authors report the case of a 35-year-old patient
      with a known history of rheumatic fever, who developed blood culture negative
      infectious endocarditis on a mitral bioprosthesis. The diagnosis of Q fever was
      based on serological arguments. Despite long-term antibiotic therapy, serology
      remained strongly positive and was associated with repeated mitral valve
      disinsertion. The patient died immediately after the fourth operation in a
      context of haemodynamic failure. This clinical case emphasizes the importance of
      performing Q fever serology in any case of culture negative endocarditis and the
      therapeutic difficulties encountered in chronic recurrent endocarditis.

PMID- 9587434
TI  - [Angiosarcoma of the right atrium. Presentation of a surgically treated case and
      comparison with data of the literature].
AB  - The authors report the case of a 28-year-old woman referred to their department
      by a respiratory medicine department with an inferior mediastinal tumour arising
      from the right atrium, presenting in the form of dysponea, dry cough and chest
      pain associated with a general syndrome composed of fever, weight loss and
      physical asthenia. Physical examination revealed a superior vena cava syndrome,
      the electrocardiogram showed diffuse repolarization disorders and the chest x-ray
      showed an opacity of the anterior and inferior mediastinum. The diagnosis of
      tumour of the right atrium was based on echocardiography and thoracic CT scan.
      Subtotal surgical resection under cardiopulmonary bypass allowed examination of
      the histological type of the tumour. After routine chemotherapy, despite negative
      secondary staging and a favourable immediate course, the patient died 11 months
      after the operation in a context of local recurrence and hepatic and bone
      metastases.

PMID- 9587435
TI  - [Auricular vulnerability: what information can be obtained from the study of
      auricular vulnerability? How to perform this study?].
AB  - The factors involved in atrial vulnerability are the presence of intra-atrial
      conduction disorders and abnormalities of refractory periods which are short,
      dispersed and poorly adapted to heart rate. All these factors are
      arrthythmogenic. The main value of the study of atrial vulnerability consists of
      investigation of unexplained ischaemic cerebrovascular accidents in young
      subjects. In practice, atrial vulnerability can be measured in the context of a
      classical endocavitary electrophysiological investigation. The stimulation and
      recording parameters must be standardized. Latent atrial vulnerability can be
      considered to be present when at least one of the following elements are found:
      significant inducibility, very short and poorly adapted effective refractory
      periods, decreased latent atrial vulnerability index.

PMID- 9587436
TI  - [Quality of life and heart failure: the quest for the Graal?].

PMID- 9587437
TI  - [Measurement of functional inability and quality of life in cardiac failure.
      Transcultural adaptation and validation of the Goldman, Minnesota and Duke
      questionnaires].
AB  - Cardiac failure has a big impact on the daily life of patients and this can be
      evaluated using quality of life questionnaires. The aim of this study was to
      translate and adapt for the French population and test the validity of two
      quality of life self-administered-questionnaires: the Duke health Profile, the
      Minnesota Quality of Life Questionnaire in Cardiac Failure and one function
      capacity questionnaire, the Goldman Specific Activity Scale. The questionnaires
      were translated and retranslated then submitted to a committee of experts: the
      final version was presented to 30 patients. The study of the quantitative
      properties of the three instruments was performed on a sample of 74 patients with
      cardiac failure to assess their validity and 26 stable patients after cardiac
      transplantation to test reproducibility. The results of this study show that
      these three instruments are valid and reproducible and are comparable to the
      original documents: Cronbach's Alpha ranging from 0.54 to 0.78 for the Duke,
      except for the social dimension, and from 0.73 to 0.93 for the Minnesota, except
      for its incapacity dimension, intraclass correlation coefficient > 0.6 in all
      dimensions. The validity of convergence with LVEF and the NYHA measured during
      hospitalisation for decompensation was poor, except for the Goldman. The three
      instruments provided coherent information. The authors conclude that a structured
      method allows transcultural adaptation of instruments of evaluation of quality of
      life, the French version having comparable properties to the original documents:
      they may be used for clinical research.

PMID- 9587438
TI  - [Early percutaneous coronary angioplasty in unstable angina].
AB  - The risks of complications of percutaneous transluminal coronary angioplasty
      (PTCA) are increased in unstable angina. Medical treatment for a few days before
      PTCA is widely adopted to reduce the risk of thrombosis or occlusive dissection
      during and after the procedure. Over the last few years, the authors have adopted
      a strategy of early coronary angiography completed by immediate angioplasty when
      possible, without waiting for the eventual benefit of aspirin or heparin therapy.
      Their experience from 1988 to 1995 of 853 patients treated by PTCA (151/853 or
      17.7%, with implantation of a stent) for unstable angina, was reviewed. Group I
      comprised 402 patients treated on the day of or the day after admission. Group II
      comprised 451 patients treated 2 days or more after admission. Patients in Group
      I were younger (62 +/- 11 vs 64 +/- 12, p < 0.001), and had single vessel disease
      more often (61 vs 52%, p < 0.005). The success rate of PTCA was similar in the 2
      groups (85.3 vs 88.2%, NS), as was the rate of complications (death, infarction
      or coronary bypass surgery, 9.9 vs 7.3%, NS). The length of hospital stay was
      significantly shorter in Group I (6.1 +/- 5.6 vs 8.7 +/- 6.9 days, p < 0.0001).
      With the limitations inherent to all retrospective studies, these data suggest
      that an early interventional approach in unstable angina has a similar success
      rate with no more complications than angioplasty. This approach is associated
      with a deferred significant decrease in the duration of hospital stay.

PMID- 9587439
TI  - [Incidence and development of aortic stenosis in chronic hemodialysis. An
      ultrasonographic and biological study of 112 patients].
AB  - Valvular calcification in chronic haemodialysis patients has already been
      reported in the literature, particularly the abnormally high incidence of aortic
      stenosis. In this study, 112 haemodialysis patients were followed up by Doppler
      echocardiography for a period of 36 months. Sixteen patients developed aortic
      valvular calcification with aortic stenosis over an 18.7 +/- 7.5 months period.
      The indexed aortic valve surface area decreased from 1.24 +/- 0.9 cm2/m2 to 0.66
      +/- 0.21 cm2/m2 with abnormally rapid progression. Eight patients with aortic
      stenosis died during the 3 year study period. These results reflect the abnormal
      extra-skeletal calcification of chronic haemodialysis patients. Several
      predisposing factors were demonstrated: age (68.5 +/- 11.1 years versus 57.1 +/-
      16.3 years in patients without calcifications), male gender, a longer period of
      dialysis than the patients without aortic stenosis (8.1 +/- 5.3 versus 5.9 +/-
      5.7 years), abnormalities of calcium and phosphate metabolism, increased of the
      phosphocalcic product by hyperphosphoraemia and not by hypercalcaemia,
      hypoparathyroidism in 62% and hyperparathyroidism in 38% an increase in vitamin D
      3 (19.7 +/- 14 ng/ml versus 9.6 +/- 6.3 ng/ml) biological signs of adynamic
      osteodystrophy. Calcific aortic stenosis is a commonly observed valvular lesion
      in haemodialysis patients: its progression may be very rapid, associated with a
      poor prognosis. Old age, male gender, duration of haemodialysis,
      hyperphosphataemia associated with hypoparathyroidism and raised Vitamin D3 are
      predisposing factors.

PMID- 9587440
TI  - [Cardioversion of atrial fibrillation with low energy internal electric shock].
AB  - The efficacy and safety of low internal cardioversion for the reduction of atrial
      fibrillation was assessed prospectively in 104 consecutive patients. Sixty-two
      patients had chronic atrial fibrillation (Group I). 16 patients had paroxysmal
      atrial fibrillation (Group II) and 26 patients had induced atrial fibrillation
      (Group III). The average duration of the current episode of atrial fibrillation
      was 9 +/- 19 months in Group I, 4 +/- 2 days in Group II and 18 +/- 7 minutes in
      Group III. Two intracardiac defibrillation catheters were used, one (the cathode)
      in the right atrium and the other in the coronary sinus or left branch of the
      pulmonary artery (anode). These catheters were connected to an external
      defibrillator delivering biphasic 3/3 ms shocks with a voltage which could be
      programmed from 10 to 400 volts. The shocks were synchronised on the R wave.
      Sinus rhythm was restored in 44 of the 62 patients in Group I (70%), 12 of the 16
      patients in Group II (75%) and 20 of the 26 patients in Group III (77%). The
      average voltages and energies restoring sinus rhythm were 300 +/- 68 volts and
      3.5 +/- 1.5 joules respectively in Group I, 245 +/- 72 volts and 2.0 +/- 2.9
      joules in Group II, and 270 +/- 67 volts and 2.6 +/- 1.2 joules in Group III.
      These results show that the energy required to restore sinus rhythm is
      significantly greater in patients with chronic atrial fibrillation than in
      patients with paroxysmal or induced atrial fibrillation. There were no
      ventricular proarrhythmic effects in the 686 shocks synchronised on the R wave.
      This study shows that internal cardioversion of atrial fibrillation is feasible
      with low energies under simple sedation. These results support the concept of an
      implantable atrial defibrillator.

PMID- 9587441
TI  - [Conservative surgery in rheumatic aortic insufficiency].
AB  - The mechanism of rheumatic aortic regurgitation is retraction of the three cusps
      leading to lack of coaptation. The authors describe a technique of aortic valve
      repair by extension of the cusps using autologous pericardium, undertaken in 52
      patients (mean age 21 +/- 5 years) and report the short and medium term results.
      There were no operative deaths or reoperation for technical failure. The
      postoperative echocardiographic examinations showed absent or minimal aortic
      regurgitation in 45 patients (87%) and moderate regurgitation in 7 patients
      (13%). The echocardiographic results at 2 years were stable: no patient was
      reoperated for deterioration of the valvuloplasty. This technique is reproducible
      and reliable is selected patients.

PMID- 9587442
TI  - [Prognostic significance of early raised cardiac troponine I in unstable angina.
      Contribution to the identification of a high-risk sub-group].
AB  - The authors compared the clinical and angiographic characteristics of 44 patients
      with unstable angina according to cardiac Troponine I concentrations (TnIc)
      during early blood sampling and then tried to determine a threshold value to
      predic the occurrence of cardiac events during the hospital period and after 12
      months. Tnlc, creatinine-kinase (CK), CK-MB activity and CK-MB mass were sampled
      over 48 hours. Forty-five per cent of patients had TnIc > or = 0.1 microgram/L;
      CK-MB activity and CK-MB mass were detected in 16 and 32% of patients. Age,
      gender, classification and recurrence of angina, previous cardiac history, risk
      factors, coronary angiographic appearances were comparable in patients with and
      without raised TnIc. No major cardiac events occurred during the hospital period
      in either group. The number of angioplasties and coronary bypass procedures was
      also comparable. At one year, the incidence of myocardial infarction (N = 4) and
      death (N = 5) was significantly different in patients with raised Tnlc (33%
      versus 0% in patients without increased TnIc). However, betablocker therapy was
      less prescribed in the group with the poorest outcomes and left ventricular
      dysfunction was also significantly more common in this group. Early elevation of
      Tnlc could contribute to the identification of a high risk subgroup of patients
      with unstable angina.

PMID- 9587443
TI  - [Echocardiographic Doppler study of left ventricular filling in the diagnosis of
      minimal or moderate rejection in cardiac transplantation].
AB  - The study of left ventricular filling by Doppler echocardiography may be a non
      invasive diagnostic method of detection of acute rejection of cardiac
      transplants. The aim of this study was to assess the value of the method for
      diagnosis of minimal to moderate rejection (grades 1 to 3 of the Billingham
      classification). A total of 466 Doppler echocardiographic studies were performed
      in 23 cardiac transplantation patients (21 men, mean age 49.3 +/- 10 years) with
      endomyocardial biopsy as the reference method for the diagnosis of rejection.
      Over a follow-up period of 18.5 +/- 10 months, 22.7% of biopsies showed minimal
      or moderate rejection. The Doppler measurements of the isovolumic relaxation
      period and peak early diastolic (E) velocity with respect to the mitral velocity
      time integral were no different in cases of acute rejection. The only difference
      observed was in the mitral half-pressure time which was much shorter in cases of
      rejection. However, after drawing a ROC graph, the accuracy of this parameter was
      insufficient for diagnosing rejection irrespective of the threshold of variation
      considered (23% sensitivity for a 20% shortening and 36% sensitivity for a 10%
      shortening). The authors conclude that Doppler echocardiographic study of left
      ventricular filling is of limited value for the diagnosis of acute minimal or
      moderate rejection in cardiac transplant patients. The half-pressure time may be
      a useful complement to endomyocardial biopsy or when biopsy investigations are
      performed less frequently.

PMID- 9587444
TI  - [Prolonged endotracheal intubation after open heart surgery under the age of one
      year].
AB  - The aim of this study was to determine the impact of prolonged endotracheal
      intubation after open heart surgery in neonates and babies with respect to the
      cardiac diseases most frequently responsible and the reasons for delayed
      extubation and the related mortality. Intubation was considered to be prolonged
      if lasting over 48 hours. This was a retrospective study of all cases of open
      heart surgery performed before one year of age between 1991 and 1996. Prolonged
      intubation was noted in 43.1% of cases (266/617). The frequency was much higher
      than in children over 1 year of age: 8.3% (56/725). Truncus arteriosus (93.5%:
      29/31), obstructed total anomalous venous drainage (93.3%: 14/15). Taussig-Bing
      anomaly (83.3%: 5/6), interruption of the aortic arch (78.9%: 15/19), double
      outlet right ventricle (61.1%: 11/18) and transposition of the great arteries
      (50.2%: 107/213) were the commonest responsible malformations. The reasons for
      delayed extubation, often multiple, were established in 222 cases: cardiogenic
      shock or circulating failure in 155 cases, pulmonary dysfunction in 142 cases,
      surgical complications in 65 cases and neurological complications in 14 cases.
      Twelve patients died: 5 of congestive heart failure, 3 of pulmonary hypertension,
      2 of septic shock and 1 of diffuse stenosis of the pulmonary veins. The mortality
      rate was 4.5% (12/266) in cases of prolonged intubation and 5.2% (32/617) for all
      infants operated during the first year of life. The authors conclude that a large
      number of infants undergoing open heart surgery undergo prolonged intubation
      because of their poor preoperative status and the particularly severe effects of
      cardiopulmonary bypass at this age. However, the associated mortality was low in
      this series.

PMID- 9587445
TI  - [Accessory pathways of decremential conduction (Mahaim fibers). Treatment by
      endocavitary ablation; apropos of 8 cases].
AB  - Mahaim fibres are rare, right sided accessory pathways comparable with respect to
      certain properties (slow, decremential conduction) with "accessory
      atrioventricular node" located on the lateral tricuspid annulus at a distance
      from the Aschoff-Tawara node. Atriofascicular and atrioventricular fibres may be
      distinguished, both responsible for wide complex tachycardia (left bundle branch
      block pattern with left axis deviation). The authors report a series of 8
      patients (6 women, 2 men: age: 27 +/- 11 years) without underlying cardiac
      disease, incapacitated by episodes of antidromic reciprocating tachycardia
      related to the atriofascicular fibres and justifying the indication of treatment
      by endocavitary ablation. In all cases, the authors tried to identify a specific
      potential of the Mahaim fibres on the lateral aspect of the tricuspid annulus.
      When the potential was recorded (7 out of the 8 cases) ablation was successful
      (procedure time 160 +/- 11 min; average number of applications: 9). It was not
      possible to identify a specific Mahaim potential in 1 case and so ablation was
      performed on the distal right ventricular site of insertion with no criterion of
      efficacy. In one woman, manipulation of the ablation catheter led to prolonged
      mechanical block in the Mahaim fibres, so suppressing the usual criteria of
      evaluation of the initial result of ablation: an early recurrence of tachycardia
      was observed in this case. No complications occurred during the 8 procedures.
      These results and those of other published cases, showed that radiofrequency
      ablation of Mahaim fibres is feasible with a high success rate without any
      immediate or long-term complications. This reliable and effective technique
      should form one of the therapeutic options for these invalidating junctional
      tachycardias.

PMID- 9587446
TI  - [Use of abciximab during coronary angioplasty].
AB  - The IIb-IIIa glycoprotein is the platelet receptor of fibrinogen and the final
      common pathway of platelet activation and aggregation. Abciximab is a Fab
      fragment of the chimeric monoclonal antibody (c7E3) interfering with the
      glycoprotein receptor. It is the only anti IIb-IIIa currently available,
      commercialized under the name of Reopro. Preliminary clinical data has been
      obtained with its use in high risk coronary angioplasty. The EPIC trial showed a
      35% relative reduction of the principal combined criterion of judgement of
      cardiac morbidity and mortality at 1 month, a benefit even greater in acute
      coronary syndromes (-72%) than in programmed procedures for complex type C
      lesions (-10%). The incidence of severe bleeding was high (14%). The results of
      the CAPTURE trial could widen the indications of abciximab to include the period
      surrounding angioplasty for unstable angina as the use of Reopro in the 24 hours
      before the procedure significantly reduced the risk of ischaemic events (10.8%
      versus 16.4%). In programmed angioplasty, the EPILOG trial investigated the
      effects of adapting the dose of heparin and an infusion of abciximab to body
      weight early (4th to 6th hour) withdrawal of the arterial introducer without
      continuing heparin. Using a 70 IU/Kg dosage modulated to algorithms taking into
      account the ACT, the incidence of bleeding complications was reduced to 1.8%, the
      same as the control group, and the benefits with regards to ischaemic events were
      not only maintained but increased (a 56% reduction at 1 months). Utilization of
      abciximab would be supported by the Cost saving approach of the EPIC trial 3
      years follow-up which showed presentation of the initial benefits.

PMID- 9587447
TI  - [Myocardial infarction in a pregnant woman during salbutamol therapy].
AB  - The authors report the case of a 31 year old woman at 30 weeks' gestation who
      developed a non-Q wave postero-lateral myocardial infarction during treatment
      with salbutamol. There were no complications and delivery took place at term
      normally. Coronary angiography was performed 3 months post-partum and was normal:
      the Methergin test was negative. Myocardial ischaemia occurring during treatment
      with a beta-2 mimetic in pregnancy is rare and hardly ever progresses to
      myocardial infarction. The usual mechanism of ischaemia is an imbalance of
      myocardial oxygen demand and supply. Myocardial oxygen consumption is naturally
      increased during pregnancy and excess intracellular calcium secondary to the beta
      1 stimulation occurring with the use of beta-2 mimetic drugs further aggravates
      matters. This hypothesis raises the question of the value of calcium inhibitors
      in these forms of myocardial ischaemia.

PMID- 9587448
TI  - [Malignant cardiac lymphoma. Diagnosis by echocardiography].
AB  - The authors report a case of cardiac malignant non-Hodgkin lymphoma. The initial
      clinical presentation suggested recurrent angina in a patient who had undergone
      angioplasty of the left anterior descending artery two years previously.
      Echocardiography showed severe left ventricular dysfunction with apical and
      septal akinesia and also allowed visualisation of two oval masses in the right
      ventricle without dilatation of the right heart chambers. Transoesophageal
      echocardiography confirmed these abnormal echos which corresponded to tumour
      invasion of not only the right heart chambers but also the interatrial septum,
      the left atrial appendage and the descending thoracic aorta. Histological
      diagnosis of lymphoma was made from an excision biopsy of a mass in the calf
      muscle. The post-mortem examination confirmed the presence of a highly malignant
      T-cell non-Hodgkin lymphoma. The patient rapidly deteriorated and died during the
      first session of chemotherapy.

PMID- 9587449
TI  - [Calcified aortic valvular disease associated with adult progeria].
AB  - Adult's progeria or Werner's syndrome is a rare condition of autosomal-recessive
      inheritance, characterized by an apparent acceleration of many of the processes
      associated with aging. We describe the cardiovascular findings in a 44 year-old
      man with this disorder. Slightly elevation of urinary hyaluronic acid level
      contributes to the diagnosis.

PMID- 9587450
TI  - [The aorta and its diseases].

PMID- 9587451
TI  - [Role of echocardiography in the diagnosis of congenital abnormalities of the
      thoracic aorta].
AB  - Echocardiography has revolutionized the diagnosis and follow-up of congenital
      heart disease over the last 20 years. Permanent technological innovation in the
      field of ultrasonic investigation and in the limitations inherent to this
      technique are illustrated in the assessment of congenital disease of the aorta,
      the subject of this review. The role of echocardiography associated with Doppler
      techniques in the investigation of congenital disease of the aorta varies with
      age: there is no rival technique in investigation of the foetus; in neonates,
      infants and young children, the role of ultrasound is preponderant because of the
      excellent echogenicity and the high incidence of congenital aortic disease
      occurring in a clinical context of cardiorespiratory distress. The limitations
      and insufficiencies of the techniques are greater in adolescents and adults in
      whom other non-invasive techniques are possible in acceptable practical
      conditions. The reality of progress in diagnosis is demonstrated by the
      possibility of therapeutic indications based only on the association of clinical
      and echocardiographic data without need for diagnostic catheterization and
      angiography. The limitations of ultrasonic techniques should however be
      recognized to avoid inappropriate usage.

PMID- 9587452
TI  - [Role of echocardiography in the diagnosis of acquired diseases of the thoracic
      aorta].
AB  - The diagnosis and follow-up of acquired thoracic aortic disease have greatly
      improved with advances in transthoracic and transoesophageal echocardiographic
      techniques. In emergency situations, transoesophageal echocardiography is the key
      diagnostic investigation for dissection, significantly speeding up surgical
      referral. Atherosclerosis of the aorta is the second clinical situation in which
      transoesophageal echocardiography confirms its superiority over other imaging
      techniques for the recognition of intra-aortic debris carrying a high embolic
      risk.

PMID- 9587453
TI  - [Role of angio-MRI in the diagnosis of thoracic aortic diseases].
AB  - MRI is a promising method of studying aortic pathology because of its non
      invasive nature and the possibility of obtaining morphological (on spin-echo
      sequences) and functional data (gradient echo with injection of contrast).
      Sequences sensitive to flow may be used to obtain angiographic-type images of the
      thoracic aorta. MRI is therefore the investigation of choice in the diagnosis and
      follow-up of dissections and aneurysms, both pre- and postoperatively. MRI allows
      differentiation between mural thrombosis and blood flow. The presence of a
      pleural effusion or of bleeding around the aorta is easily demonstrated. MRI also
      appears to be valuable in the assessment of aortic arch abnormalities because of
      its wide field of vision and its different spatial planes.

PMID- 9587454
TI  - [Marfan's syndrome. Cardiovascular manifestations and therapeutic indications].
AB  - Marfan's syndrome is a disease of collagen microfibrils, the essential
      composition of which, fibrillin, is defective. The coding gene of this large
      protein has been localised on chromosome 15 and partially cloned. Its mutation is
      transmitted in the autosomal dominant mode. It is common, affects many organs,
      especially those rich in collagen. They include the skeleton, the eye and
      cardiovascular system. The prognosis of these patients depends on the degree of
      cardiovascular involvement; the aorta is the principal site of the lesions,
      particularly the aortic root which tends to develop aneurysmal dilatation, then
      dissection, the main cause of premature death of these patients. Mitral valve
      prolapse giving rise to mitral regurgitation may also be observed. Much progress
      has been made is recent years in the management of Marfan's syndrome, especially
      in ultrasound follow-up of the aortic root and the definition of risk factors for
      dissection. In parallel, advances have been made in the treatment, both medical
      with the use of betablockers to try to slow progression to aneurysm, and
      surgical, in replacement of the aorta and aortic valve in time and under optimal
      conditions. Life expectancy is thereby significantly increased. Similar progress
      has been made to allow these patients to have a pregnancy, classically thought to
      carry a high risk of maternal death.

PMID- 9587455
TI  - [Contribution of genetics to pathogenicity and diagnosis of Marfan syndrome].
AB  - The anatomical substrate of Marfan's syndrome is a degeneration of elastic fibres
      and disorganization of the collagen. It is now known that these lesions are due
      to mutation of genes localised on chromosome 15. The first of them (FBN1) codes
      for the main constitutive protein of the elastic tissue: fibrillin 1, present
      mainly in structures which must resist load and stress (aortic adventitia, the
      suspending ligament of the lens, skin); the second (FBN2) codes for fibrillin 2:
      responsible for the orientation of the elastin and mainly present in cartilage,
      the aortic media, the bronchi, and all tissues rich in elastin. Mutations of FBN1
      are very common and are associated not only with Marfan's syndrome but also
      fibrillinopathies: incomplete forms, neonatal forms, ectopic lens, isolated
      aneurysms of the thoracic aorta. The widespread distribution of fibrillin
      explains the pleiotropic nature of Marfan's syndrome and its clinical
      presentation. The variability of interfamilial expression is due to genetic
      heterogeneity (at least two genes) and alletic differences (different mutations
      of FBN1 from one family to another), also explaining mild forms due to
      quantitative reduction in normal fibrillin and severe forms by "negative
      dominance" where the fibrillin is structurally abnormal because of alteration of
      the polymerisation mechanism. The biologic diagnosis of fibrillopathy can be made
      by a protein test analysing fibrillin on a culture of the patient's fibroblast
      obtained by skin biopsy. At present, molecular diagnosis of the mutation within
      the FBN1 gene is not feasible as a routine procedure.

PMID- 9587456
TI  - [Thoracic aortic aneurysm in Marfan syndrome].
AB  - Thoracic aortic aneurysms are the main cardiovascular complication of Marfan's
      syndrome. Elastic tissue dystrophy of the ascending aorta is responsible for
      appearances of cystic medial necrosis in the major forms. Dilatation of the
      ascending aorta is progressive with time. The risk of dissection and rupture, an
      acute complication of Marfan's syndrome, is very high when the aortic dilatation
      reaches 60 mm, although dissection may be observed with dilatation of 50 mm.
      Aortic regurgitation is found in half the cases. Echocardiography, CT scan and
      MRI provide accurate assessment of the anatomy of the lesions and help in
      following up the dilatation. Betablocker therapy slows down the progression of
      the dilatation. Bentall's procedure was first described in 1968 with its
      technical variants for reimplantation of the coronary arteries: Cabrol's
      procedure, technique of periostal lean-to, the button technique, are major
      advances in the surgical treatment of ascending aortic aneurysms. The life
      expectancy is reported to be about 90% at 5 years and 75 to 80% at 10 years.
      Reoperation is sometimes necessary because of pseudo-aneurysms occurring as a
      late complication at the operation site or because of other aneurysms developing.
      Progress in the field of genetics is a hope for the future.

PMID- 9587457
TI  - [Long-term results after surgery of coarctation of the aorta in neonates and
      children].
AB  - Surgery is the treatment of choice for coarctation of the aorta in childhood.
      Coarctation presenting in the neonatal period carries a poorer functional and
      vital prognosis and it may be opposed to the paucisymptomatic forms observed in
      infants and children. Coarctation in the neonatal period presents with severe
      cardiac failure and is often associated with hypoplasia of the transverse aorta
      and/or other complex congenital malformation. Improved neonatal intensive care
      and the introduction of prostaglandin E1 have considerably reduced the immediate
      mortality by enabling surgery to be undertaken under the best possible
      haemodynamic conditions. However, early and late mortality in this group remain
      significantly higher due to associated cardiac lesions; in this context, the
      management varies with some groups carrying out surgery in one stage and others
      in two stages. Despite progress in neonatal surgery and operative techniques to
      increase the diameter of the transverse aorta, hypoplasia may persist and be a
      cause of restenosis or secondary hypertension. In this group of coarctations, the
      main problem is the timing of surgery in order to reduce the risks of restenosis
      and hypertension to a minimum. Restenosis is diagnosed by clinical examination.
      Doppler ultrasonography and eventually confirmed by magnetic resonance imaging
      (MRI). The risk factors for restenosis are young age at surgery, the type of
      procedure performed and the presence of extensive aortic hypoplasia. Recurrent,
      localised forms are accessible to percutaneous angioplasty when performed 6
      months to 1 year after surgery; extensive restenosis and restenosis in older
      children should be referred for reoperation. Some subjects become hypertensive in
      the absence of residual obstruction and, in these cases, MRI should be requested
      to detect hypoplasia of the aortic arch. However, hypertension may be observed
      alone or only occur during exercise: late surgery and the length of follow-up
      seem to be associated with its occurrence. Aortic aneurysms occur after
      aortoplasty with a patch, a technique which has now be abandoned for this reason.
      Nevertheless, this risk is also associated with percutaneous angioplasty of
      restenosis, justifying systematic diagnostic MRI. In summary, coarctation of the
      aorta in children has a good overall prognosis at medium-term, the neonatal forms
      having considerably benefited from progress in the management of this condition
      in the intensive care unit and from advances in surgical technique. However, long
      term cardiological follow-up remains necessary to detect the two potential
      complications: restenosis and hypertension.

PMID- 9587458
TI  - [Coarctation of the aorta and its surgical treatment].
AB  - Coarctation or isthmic stenosis of the aorta is defined as an abnormal
      obstruction situated at the junction of the aortic arch and the descending aorta
      near the site of ligamentus arteriosus. It is a common malformation representing
      5 to 7.5% of all congenital heart diseases. Coarctation of the aorta is 2 to 3
      times commoner in boys than in girls. Two clinical forms may be distinguished:
      asymptomatic isolated coarctation of childhood, the surgical treatment of which
      was first performed by Crafoord in 1944, and coarctation of the neonate and
      infant associated in over 2/3 of cases with other cardiovascular malformations,
      especially tubular hypoplasia of the aortic arch. The surgical correction of
      isolated coarctation is best performed between 6 months and 1 year of age in
      other to limit the incidence of residual hypertension. A modified Crafoord
      technique decreases the risk of restenosis and enables treatment of associated
      hypoplasia of the aortic arch in the same surgical procedure.

PMID- 9587459
TI  - [Post-traumatic aneurysms of the thoracic aorta].
AB  - Traumatic rupture of the sub-advential tunics (intima, media) of the thoracic
      aorta is rarely observed in the chronic phase (5% of survivors). Organisation of
      the lesion with thickening and ballooning of the adventitia results in post
      traumatic aneurysmal formation of the thoracic aorta, situated at the aortic
      isthmus in the large majority of cases. The diagnosis is usually a chance finding
      on chest X-ray several years later. CT scan, but mostly MRI and angiography
      confirm the diagnosis. Their natural history is the same as that of dystrophic
      and atheromatous aneurysms and dominated by the risk of rupture. The surgical
      indication should therefore be considered systematically as the treatment is well
      established and the postoperative prognosis in excellent (mortality rate of 0 to
      2%. Treatment consists in implanting a Dacron tubular prosthesis and, when
      possible, reaction and direct suture.

PMID- 9587460
TI  - [Atheromatous aneurysms of the thoracic aorta].
AB  - Atheromatous aneurysms of the thoracic aorta are much less common than those of
      the abdominal aorta. Associated atherosclerosis of the coronary, cerebral and
      peripheral limb arteries is observed in 16, 10 and 11% of cases, respectively.
      Ultrasonography. CT scanning, and mostly MRI and digitised angiography provide
      very accurate morphological data. The natural history is dominated by the risk of
      rupture with a 3 year survival of 50% in aneurysms with a diameter superior to 5
      cm. The surgical indication should be considered in cases of aneurysms with
      diameters over 5 cm after full carotid, coronary, respiratory and renal
      investigations. Surgery is simple in descending aortic aneurysms but more
      complicated in aneurysms of the transverse and descending aorta, especially in
      long lesions. Technical innovations have reduced the incidence of both cerebral
      complications after surgery of the aortic arch by improved cerebral protection
      and of medullary complications after surgery of the descending thoracic aorta,
      especially of thoraco-abdominal aneurysms, by better medullary protection against
      ischaemia during aortic clamping. The operative results have a mortality of: 3%
      for aneurysms of the ascending aorta: 10% for aneurysms of the aortic arch: 9%
      with a 15% risk of paraplegia, for long aneurysms of the descending thoracic
      aorta.

PMID- 9587461
TI  - [Inflammatory aneurysms of the thoracic aorta. Surgical aspects].
AB  - In the Western world, inflammatory aneurysms account for only 1 to 5%, of all
      operated thoracic aorta aneurysms. Takayasu's disease is by far the commonest
      cause although all forms of aortitis may result in aneurysm formation. Usually
      observed in young patients, these aneurysms are suitable for often major surgery
      with results that are globally better than in degenerative or dissecting
      aneurysms. However, they pose, two specific problems: the progression of the
      inflammatory disease which may require pre- and/or post-operative steroid therapy
      and that of the risk, at least in theory, of a late pseudo-aneurysm, which
      justifies regular long-term follow-up after surgery.

PMID- 9587462
TI  - [Chronic dissection of the thoracic aorta. Diagnosis, management and prognosis].
AB  - Dissection of the thoracic aorta becomes chronic after the 14th day following the
      first signs of dissection. It may be "primary", that is to say diagnosed at the
      chronic stage, the acute stage having passed undiagnosed, or "secondary" because
      the dissection diagnosed in the acute period was treated medically or surgically.
      Its outcome depends on the evolution of the false lumen which may thrombose or
      remain patent and stable or increase in size and progress to a false aneurysm.
      Management consists in following up the outcome of the false lumen by successive
      examination every 6 to 9 months: in general, CT scan or magnetic resonance
      imaging are used for this follow-up; transoesophageal echocardiography is another
      possibility but, when repeated, is not always accepted by the patients.
      Antihypertensive therapy is essential as it improves long-term survival in all
      cases. Surgery is justified but the operative risk is high should an acute
      complication occur with an immediate threat to life. This indication should be
      maintained in symptomatic patients (signs of compression of a false aneurysm,
      painful reactivation) after thorough preoperative preparations, given the poor
      prognosis of the natural history of chronic dissection of the thoracic aorta
      irrespective of its site. In asymptomatic patients with aortic diameters of more
      than 60 mm in the first segments of the aorta (ascending or transverse aorta),
      surgery provides better long-term survival rates than medical management. In
      disease of the descending thoracic aorta, no difference in survival is observed
      between medical or surgical treatment: the surgical indication should be more
      conservative, especially because of the high incidence of neurological
      complications (paraparesis-paraplegia) in the absence of peroperative medullary
      protection, which is always reproducible, effective and validated.

PMID- 9587464
TI  - [Surgical replacement of the aortic arch].
AB  - Deep hypothermia with circulatory arrest is the usual method of cerebral
      protection during replacement of the aortic arch. However, this technique only
      gives the surgeon a limited period of time to carry out aortic repair. It also
      requires that cardiopulmonary bypass be prolonged to rewarm the patient which may
      cause many complications. Selective carotid artery perfusion may also be used.
      When this perfusion is derived from the principal arterial line the aorta must be
      clamped to perform the repair. In addition, there is some uncertainly as to what
      constitutes adequate cerebral perfusion at normal temperature or during moderate
      hypothermia. In order to reconcile the advantages of both methods whilst avoiding
      the disadvantages, the authors described a new technique of cerebral protection
      in 1984. The principle was to selectively perfuse the carotid arteries with blood
      cooled to 6 to 12 degrees C via a separate heat exchanger while maintaining the
      central temperature in moderate hypothermia (25 to 28 degrees C rectal). In order
      to carry out an "open" distal anastomosis, the main cardiopulmonary bypass is
      stopped whilst carotid perfusion is maintained (350 to 500 ml/min). When the
      distal anastomosis has been completed, general cardiopulmonary bypass is
      restarted and the patient rewarmed. Using this technique. 158 patients aged 25 to
      83 (average 55 years) were operated between January 1984 and July 1997. The
      operative indications were for different anatomic situations (114 patients had
      chronic lesions and had planned operation and 50 patients were operated as an
      emergency for acute dissection of the ascending aorta requiring replacement of
      the aortic arch). The average duration of cardiopulmonary bypass was 121 minutes
      and the duration of circulatory arrest was 31 minutes. The electroencephalogram
      recorded continuously during these operations showed return of cerebral activity
      after an average of 12 minutes and perfectly normal activity after an average of
      66 minutes. The hospital mortality was 17% (27 deaths). Death was directly
      related to a neurological accident in 6 patients. All the others recovered within
      a normal period and were perfectly conscious at the 24th hour. Twenty non-lethal
      neurological complications were observed. The type of lesion, age and gender had
      non significant influence on the outcome of the patients: neither did the
      duration of circulatory arrest and of cerebral perfusion. No correlations could
      be established between the duration of cerebral perfusion and the frequency of
      neurological complications. In the authors' experience, the technique of
      selective anterograde perfusion of the brain with cooled blood during surgery of
      the aortic arch has shown its value. It does not require prolonged
      cardiopulmonary bypass and does not limit the time available to repair of the
      aorta. It should therefore be considered to be the method of choice for cerebral
      protection during this type of surgery.

PMID- 9587463
TI  - [Current treatment of acute dissections of the ascending aorta].
AB  - In 1977, the authors introduced the gelatin resorsin formol glue for emergency
      surgery of dissection of the ascending aorta (Stanford Type A). This special
      issue devoted to surgery of the thoracic aorta gives them the opportunity of
      summarising the different techniques of replacing the ascending aorta, underlying
      the procedures available for reinforcing the sutures. The value of the gelatin
      resorcin formol glue extensively described and the authors then analyse the
      principles and methods of treating aortic insufficiency and of the extension of
      replacement of the aorta to the aortic arch. Based on these techniques, the
      authors report their experience over a period of 20 years. Between January 1977
      and July 1997, 193 patients (139 men and 54 women) aged 15 to 79 (average 53
      years) were operated for acute dissection of the ascending aorta. All the
      operations were undertaken as an emergency and 84% within 4 hours of arrival at
      the hospital. Twenty-eight patients had typical Marfan's syndrome. The ascending
      aorta was replaced in all cases and the aortic stumps reinforced with GRF glue in
      99% of them. Forty-three patients underwent aortic valve replacement either
      separately (5 patients: 2.5%) or with a valved tube (35 patients: 19.5%). More
      recently, 3 patients underwent complete replacement of the ascending aorta with
      reimplantation of the coronary arteries and conservation of the natural valve. In
      view of the localisation or the extension of the intimal tear, complete
      replacement of the ascending aorta was extended to the aortic arch in 58 patients
      (30%). The global hospital mortality was 21% (23% in patients undergoing
      replacement of the aortic arch and 20.3% in patients undergoing replacement of
      the ascending aorta with or without aortic valve replacement N.S.). The patients
      were followed up for 2 months to 19 years (average 85 +/- 66 months). During the
      observation period, 23 patients (15%) were reoperated and underwent 29
      reoperations. Six patients died during reoperation. Late mortality was observed
      in 36 patients (23.7%) giving a global actuarial survival (Kaplan-Meier-95%
      confidence interval) was 96.5% 87.6%, 80.9%, 66.4% at 1, 5, 10 and 15 years
      respectively. The clinical status of the 116 survivors is satisfactory. Eighty
      two patients (71%) are in functional Classes I or II. Surgery of acute dissection
      of the ascending aorta remains difficult and associated with high mortality and
      morbidity. The use of GRF glue has significantly improved the immediate results
      and has made extension of surgery to sections of the aorta otherwise
      inaccessible, a reality. Nevertheless, the patients should be followed up
      indefinitely by regular non-invasive methods and maintained on betablocker
      therapy.

PMID- 9587465
TI  - [Acute dissection of the thoracic aorta. Symptoms and complications].
AB  - Acute dissection of the aorta is an increasingly recognised pathology, the
      diagnosis of which is sometimes delayed despite the fact that advances in medical
      imaging provide almost perfect diagnostic accuracy. Some of the symptoms are
      particularly suggestive. Chest pain is the key symptom, and the greater the
      intensity, usually described as a migratory intrathoracic tearing sensation
      irradiating towards the lumbar region. The other symptoms become meaningful in
      association with this pain: paraplegia, acute peripheral ischaemia, hemiplegia.
      Clinical examination is capital when a diastolic murmur of aortic regurgitation
      is heard or when a distal pulse is absent, the blood pressure is asymmetric or a
      pericardial rub is detected. The frighteningly poor initial prognosis of acute
      dissection of the aorta has been transformed by surgery, providing, that it is
      performed early. Optimal therapeutic results can only be obtained by and early
      diagnosis.

PMID- 9587466
TI  - [Empirical validation of the hypothesis that lead to the quest for the Graal?].

PMID- 9587467
TI  - [Equity and health planning: critical analysis of the SROS and implications for a
      model of resource allocation].

PMID- 9587468
TI  - [Trial of allocation resource at a sub-regional level].

PMID- 9587469
TI  - [Diffusion of a new medical technology and its stakes: example of the intra
      cytoplasmic injection of spermatozoa].

PMID- 9587470
TI  - [Empirical analysis of ambulatory care demand at the micro-economic level].

PMID- 9587472
TI  - [Physician-patient relationship: an assessment based on the theory of game].

PMID- 9587471
TI  - [Supplier-induced in ambulatory medicine: empirical evidences from the French
      context].

PMID- 9587473
TI  - Myasthenic nicotinic receptor mutant interpreted in terms of the allosteric
      model.
AB  - An extended Monod-Wyman-Changeux allosteric-type model is applied to human muscle
      nicotinic acetylcholine receptors expressed in HEK cells, for both the normal
      form and the high-affinity human myasthenic mutant, epsilon T264P. The model is
      based on a concerted transition between the basal (resting) B state and the
      active (open-channel) A state, with the equilibrium in the absence of ligand
      determined by the allosteric constant, L0 = [B0]/[A0]. For wild-type receptors
      the model with L0 = 9 x 10(8) provides a satisfactory representation of published
      patch-clamp recordings that yields a distribution of open-channel dwell times
      with a single peak at 0.7 ms. For the epsilon T264P mutant, the model with L0 =
      100 accounts for the trimodal distribution reported for open-channel dwell times,
      with peaks at 0.15, 3.8 and 60 ms that correspond to non-, mono- and bi-liganded
      receptors, respectively. Possible applications of the allosteric model to other
      myasthenic mutants are considered.

PMID- 9587474
TI  - The sarco(endo)plasmic reticulum Ca(2+)-ATPase gene is regulated at the
      transcriptional level during compensated left ventricular hypertrophy in the rat.
AB  - In mammalian myocardium, relaxation is mainly triggered by the reuptake of
      calcium from the cytosol to the lumen of the sarcoplasmic reticulum (SR) through
      the cardiac isoform of the sarco(endo)plasmic reticulum calcium ATPase, SERCA2a.
      Relaxation abnormalities related to deficient SR Ca(2+)-uptake have been
      identified in human heart failure and in animal models of cardiac hypertrophy and
      failure. These alterations have been associated with a reduction in SERCA2a
      activity and in steady-state SERCA2a protein and mRNA levels. As a first step in
      the analysis of the mechanisms responsible for this reduction, we have studied a
      possible down-regulation of the SERCA2 gene transcription during left ventricular
      hypertrophy (LVH) induced by constriction of the ascending aorta in the rat.
      Quantifications of the mRNA levels demonstrated no alteration, compared to sham
      operated rats, at 5 d after imposition of the pressure overload, whereas a
      significant decrease was observed at 11 d. Transcription in-vitro experiments
      (cardiac nuclear run-on assays) performed in isolated cardiomyocytes nuclei
      showed no changes at 5 d and a 37% reduction of the SERCA2 gene transcription at
      11 d. These results strongly suggest that SERCA2 gene expression down-regulation
      during cardiac hypertrophy occurs, at least in part, at the level of the
      transcription.

PMID- 9587475
TI  - Prion immunoreactivity in brain, tonsil, gastrointestinal epithelial cells, and
      blood and lymph vessels in lemurian zoo primates with spongiform encephalopathy.
AB  - We report on two animals of a non-human primate species Eulemur fulvus
      mayottensis, housed in the local zoo and fed over a number of years with a food
      containing cattle meat, that developed serious neurological symptoms associated
      with prion immunoreactivity in brain and various viscera. Microscopy of the
      brains showed neuronal vacuolation with patchy/perivacuolar immunolabelling with
      an abnormal isoform of prion protein (IR-PrP), an important characteristic of
      spongiform encephalopathy. For the first time, we report the presence in the same
      severely ill animals of IR-PrP in the gastrointestinal tract, detected by
      immunocytochemistry with mono- and polyclonal antibodies directed against various
      parts of the PrP. Strong PrP labelling was observed in the epithelial cells
      lining the pharyngeal and gastrointestinal lumen. The tonsils and the walls of
      the lymph and blood vessels below the intestinal epithelium were also labelled.
      There were no such immunoreactions in healthy lemurians killed as controls, i.e.
      a younger congener of the same species housed under the same conditions, and
      others belonging to the smaller species Microcebus murinus, reared in the
      laboratory and never fed on commercial food products containing cattle meat.
      These results demonstrate a strong PrP accumulation in the brain, the
      gastrointestinal tract and underlying lymphoreticular structures in these
      primates living in a zoological park and suffering from a spongiform
      encephalopathy.

PMID- 9587476
TI  - Phenotypic characterization of Leishmania mexicana pentamidine-resistant
      promastigotes. Modulation of the resistance during in-vitro developmental life
      cycle.
AB  - Two clones of Leishmania mexicana resistant to 5 microM (LmR5CL2) and 20 microM
      (LmR20CL1) pentamidine, derived from a parental wild-type clone (LmWTCL3) were
      selected in vitro using a continuous drug pressure protocol. Both resistant
      clones expressed a cross-resistance to diminazene aceturate. No differences in
      their in-vitro infectivity for mouse peritoneal macrophages between wild-type and
      pentamidine-resistant promastigotes were observed. During these experiments,
      promastigotes of LmR20CL1 derived from intramacrophagic amastigote forms reverted
      to the pentamidine-sensitive phenotype, unlike the lower resistant ones. In the
      same way, when a complete developmental sequence of L. mexicana was achieved in
      axenic cultures, LmR20CL1 promastigotes derived from axenically growing
      amastigotes expressed an IC50 value close to the wild-type one, whereas resulting
      LmR5CL2 promastigotes remained pentamidine resistant. This modulation of the
      chemoresistance during the developmental life cycle could be significant in the
      transmission of drug-resistant strains by Phlebotominae as well as in basic
      research to follow drug resistance during the in-vitro and in-vivo life cycle of
      Leishmania.

PMID- 9587477
TI  - Orientation responses to biological odours in the human newborn. Initial pattern
      and postnatal plasticity.
AB  - The initial pattern and development of odour preference was studied in infants
      simultaneously exposed to amniotic fluid (AF) and maternal lacteal secretion (L).
      Five groups of varying age (range: 1-5 days) and breast-feeding experience
      (range: 0-32 feeds) were studied. Before postnatal day 3, no evidence of
      differentiation of AF and L was apparent. After 3 days and 7-12 breast-feeding
      episodes, a significant preference for L arised. The initial stage (days 1-3) may
      reflect fetal acquisition of AF odour and sensory/motivational equivalence of AF
      and L odours. The second stage (days 4-5) may reflect the infants' perception of
      change in milk quality and increasing experience with milk. This sequential
      development attests to a high plasticity in the initial stage of human olfactory
      development.

PMID- 9587478
TI  - [Strategy of post-traumatic repairing of the spinal cord. General introduction].

PMID- 9587479
TI  - [Can transplantation of neurons facilitate motor recovery in paraplegics? Study
      of an animal model].
AB  - This review strives forward at least two goals. First, to take from the
      literature the arguments demonstrating that hindlimbs locomotion is controlled by
      a spinal network of neurons (the so-called Central Pattern Generator for
      locomotion--CPG) known to be able to generate locomotor activity independently of
      the control of supraspinal nervous structures, as it is after thoracic lesions of
      the spinal cord. The principles of work of the CPG and its intrinsic
      possibilities to adapt its working are reviewed. Special reference is made to the
      various ways used during experiments to activate the CPG in spinal animals or
      clinical practice in paraplegic men: training to walk, electrical stimulations,
      pharmacological stimulations. Second, to show, from our own results, obtained
      from the study of an animal model of paraplegia, the adult spinal rat, how it
      could be possible to take advantage of the autonomy of the CPG, with special
      reference to its sensibility to monoamines, to obtain locomotor recovery in
      hindlimbs after section of the thoracic spinal cord, by means of transplantation
      of noradrenergic and/or serotonergic embryonic neurons in the lumbo-sacral spinal
      cord. Section of the spinal cord at a thoracic level results in an important
      locomotor deficit in hindlimbs, likely linked to degeneration of monoaminergic
      terminals in the lumbar enlargement. In the adult spinal rat, sub-lesional
      injection of a suspension of embryonic nervous cells, taken from either locus
      coeruleus or raphe sites, leads to reinnervation of the lumbar enlargement with
      monoaminergic terminals. Despite the fact that connections with supraspinal
      structures are not reestablished, transplanted animals recover progressively a
      posture convenient for locomotion. The hindlimbs, which are in an extended
      position a few days after the lesion, become progressively flexed and able to
      support the body weight. This evolution does not appear in spinal but non
      transplanted animals. But, the main point is that transplanted animals develop,
      within the few weeks that follow transplantation, a good-quality locomotor
      activity in hindlimbs which had no equivalent in spinal but non transplanted
      animals. The reality of a lumbar CPG for locomotion and the efficacy of
      pharmacological treatments and training to walk, to elicit recovery of stepping,
      are discussed in man, in connection with the relevance to use transplantation of
      monoaminergic nervous cells in the spinal cord of paraplegics.

PMID- 9587480
TI  - [Regrowth of central respiratory pathways in neural graft. From research tool on
      the axonal regeneration to a strategy of post-traumatic reparation].
AB  - This review focuses on the regrowth of respiratory pathways after nerve grafting
      within the central nervous system of the adult rat. After a general presentation
      of the background and of the grafting procedure, we summarize our nerve grafting
      results of while it is now well established that severed axons of adult central
      neurons can regenerate within segments of peripheral nerve partially implanted
      within the brain or spinal cord, the functional properties of the regenerating
      neurons remain generally unknown. With a view to assessing the extent to which
      the functional capacities of central neurons can be maintained after axonal
      regeneration, we have carried out experiments on central respiratory neurons
      which are a good example of a highly organized neuronal network with
      characteristic patterns of spontaneous discharge. We have shown that axonal
      regrowth of central respiratory neurons was successfully induced in blind-ended
      medullary and spinal autografts implanted respectively within the respiratory
      centers of the medulla oblongata and within the cervical spinal cord at the level
      of descending respiratory pathways. The grafts consisted of true "supplementary
      nerve" in which normal afferent and efferent respiratory pathways were confirmed
      by recording respiratory unitary discharges from teased fibers within the grafts.
      The efferent discharges reflected the activity of central respiratory neurons
      that had regenerated axons within the grafts: these neurons manifested
      spontaneous activity and normal responsiveness to respiratory stimuli that
      resemble those of normal respiratory cells. In order to evaluate the possibility
      of experimental nerve banking, the feasibility of using short-term and long-term
      stored nerves as potential spinal nerve grafts was established using in vitro pre
      degenerated nerve and cryopreserved nerve grafts after assessment of Schwann cell
      viability. The extent of respiratory reinnervation of the different grafts
      (medullary, spinal and stored nerve grafts) was compared. The discussion focuses
      on the main data and the strategy for future nerve grafting is evoked: functional
      characteristics of regenerating respiratory axons, extent of graft reinnervation,
      functional schwann cell survey within stored/grafted nerve and post-traumatic
      grafting.

PMID- 9587481
TI  - [Post-traumatic reconnection of the cervical spinal cord with skeletal striated
      muscles. Study in adult rats and marmosets].
AB  - In an attempt at repairing the injured spinal cord of adult mammals (rat, dog and
      marmoset) and its damaged muscular connections, we are currently using: 1)
      peripheral nerve autografts (PNG), containing Schwann cells, to trigger and
      direct axonal regrowth from host and/or transplanted motoneurons towards
      denervated muscular targets; 2) foetal spinal cord transplants to replace lost
      neurons. In adult rats and marmosets, a PNG bridge was used to joint the injured
      cervical spinal cord to a denervated skeletal muscle (longissimus atlantis [rat]
      or biceps brachii [rat and marmoset]). The spinal lesion was obtained by the
      implantation procedure of the PNG. After a post-operative delay ranging from 2 to
      22 months, the animals were checked electrophysiologically for functional
      muscular reconnection and processed for a morphological study including
      retrograde axonal tracing (HRP, Fast Blue, True Blue), histochemistry (AChE,
      ATPase), immunocytochemistry (ChAT) and EM. It was thus demonstrated that host
      motoneurons of the cervical enlargement could extend axons all the way through
      the PNG bridge as: a) in anaesthetized animals, contraction of the reconnected
      muscle could be obtained by electrical stimulation of the grafted nerve; b) the
      retrograde axonal tracing studies indicated that a great number of host cervical
      neurons extended axons into the PNG bridge up to the muscle; c) many of them were
      assumed to be motoneurons (double labelling with True Blue and an antibody
      against ChAT); and even alpha-motoneurons (type C axosomatic synapses in HRP
      labelled neurons seen in EM in the rat); d) numerous ectopic endplates were seen
      around the intramuscular tip of the PNG. In larger (cavitation) spinal lesions
      (rat), foetal motoneurons contained in E14 spinal cord transplants could
      similarly grow axons through PNG bridges up to the reconnected muscle. Taking all
      these data into account, it can be concluded that neural transplants are
      interesting tools for evaluating both the plasticity and the repair capacities of
      the mammalian spinal cord and of its muscular connections.

PMID- 9587482
TI  - [Bovine spongiform encephalopathy and natural scrapie].
AB  - Scrapie in sheep and Bovine Spongiform Encephalopathy in cattle are
      neurodegenerative diseases. They belong to the group of transmissible spongiform
      encephalopathies (prion diseases). Scrapie is a worldwide enzootic disease, first
      described two centuries ago. It is due to more than 20 different strains of agent
      and strongly influenced by genetic factors of the host. There is no evidence of a
      link between this disease and human transmissible spongiform encephalopathies.
      Bovine Spongiform Encephalopathy is a consequence of oral infection of cattle by
      meat and bone meal produced in the United Kingdom and contaminated by the agent.
      The strain is unique and has been selected and massively amplified in the
      alimentary chain. It is probably linked to a new variant of Creutzfeldt-Jakob
      disease in man. It is expected that the ban on the incorporation of animal
      proteins in the alimentation of ruminants will soon eradicate it, although the
      risk of potential mutants of the disease and its possible transmission to sheep
      and goats exists.

PMID- 9587483
TI  - [Repair of oxidized guanine in mammals: OGG1 genes].
AB  - This paper reviews the present state of the studies on the repair of a major
      oxydative lesion on DNA, the 8-oxo-guanine (8-OxoG). This modified base has been
      proved to be highly mutagenic and therefore implicated in the ethiology of
      several pathologies. The cloning of the yeast OGG1 gene, a functional homolog of
      the fpg from bacteria, allowed the isolation of the mammalian homologs. These
      genes code for 8-OxoG DNA glycosylases/lyases, whose biochemical properties are
      consistent with their postulated role as the main defence against the genetic
      instability induced by the presence of 8-OxoG in DNA. This, together with the
      mutator phenotype of the yeast ogg1 mutant strains, make of the human OGG1 a
      candidate for a cancer predisposition gene. The localization of this gene to
      chromosome 3p and other evidences discussed in this paper indicate that OGG1
      could be a tumor suppressor gene implicated in lung cancer.

PMID- 9587484
TI  - [Radiotoxicology].
AB  - Radiotoxicology is a science aiming firstly to estimate the biological effects
      induced by radiation in workers and general population after internal
      contamination of radionuclides, secondly evaluate the risk on health. After
      internal contamination, the analysis of biokinetics of radioactive compounds
      allow to understand their behaviour in the body. Those complex processes describe
      routes of radionuclide intake, direct blood uptake or transfer of soluble form to
      blood from deposit area, urine and fecal excretions, distribution and retention
      of radionuclides in different target organs. These processes are modelled to
      establish mathematical calculations. Data obtained are important to the
      interpretation of bioassay measurement for initial activity deposit expressed in
      becquerel (Bq: transformation.s-1) and committed effective dose calculation,
      expressed in sievert (Sv). This committed effective dose corresponds to the
      absorbed dose expressed in gray (Gy), weighted by a radiation weighting factor
      related to the quality of radiation and a tissue weighting factor which
      represents the contribution of the target organ to the total detriment due to
      effects induced by uniform irradiation of the whole body. This committed
      effective dose is a specific parameter for risk assessment which characterizes
      the radiotoxicology as a special part of toxicology.

PMID- 9587485
TI  - [Physiopathology of human superficial radiation-induced fibrosis].
AB  - The radiation-induced fibrosis is a late sequela of both therapeutic and
      accidental irradiations, and has been described in several tissues such as skin
      and underlying sub-cutaneous tissues, and lung. Based on the newest findings
      arising from cellular and molecular radiobiology, this review synthesis different
      aspects of the human superficial radiation-induced fibrosis: clinical and
      paraclinical observations, radiobiological aspects, gross histological changes,
      cellular and molecular regulations, and medical management. However, the
      underlying mechanisms of the superficial radiation-induced fibrosis still remain
      to be resolved.

PMID- 9587486
TI  - [From knowledge about risk to the regulation of exposures to ionizing radiation].
AB  - Implementation of radiological protection principles has been introduced in
      French law in several ordinances during the last thirty years. They take in
      consideration: protection of the workers, including dose limitation, radiological
      quality control, individual dosimetry practices and features of medical survey;
      protection of the members of the public, including dose limitation, authorized
      levels of radioactive effluents from nuclear plants and reference levels for
      radioactive sources in the environment. Patients exposure is considered through
      several administrative recommendations taken from European Directive 84/466 from
      EURATOM. Future generations are not considered explicitely, up to now. Following
      a reappraisal of risk assessment by different scientific bodies new
      recommendations and new operational concepts have been provided by International
      Commission of Radiological Protection. They were directly transposed in European
      Directives. Implementation of European Directives 96/29 and 97/43 in national law
      will modify greatly the general architecture of French nuclear legislation which
      has been built up layer after layer without taking its roots in the bases of
      administrative, penal and civil laws.

PMID- 9587487
TI  - [Study of gene expression of melanin-concentrating hormone and of dynorphin in
      the rat hypothalamus by multiplex competitive RT-PCR].
AB  - Melanin-concentrating hormone (MCH) and dynorphin genes are expressed in two
      discrete neuron populations of the rat lateral hypothalamus. Their roles remain
      hypothetical in mammals. In order to analyze changes in MCH and dynorphin gene
      expression, we developed a multiplex competitive semi-quantitative RT-PCR
      allowing to study simultaneously the variations of their mRNAs. This technique
      was used to examine MCH and dynorphin mRNAs contents in rats food-deprived for 24
      or 48 hours as compared to controls. A 2-fold induction of dynorphin mRNA by 24
      hours, followed by a sharp decrease at 48 hours and return to control level were
      observed. A moderate increase in MCH mRNA content was noticed by 24 hours. A 48
      hours fasting restored the control levels.

PMID- 9587488
TI  - [Effect of silibinin on oxidative damage of blood constituents].
AB  - Silibinin (SDH) is a flavonoid with ascertained hepatoprotective effects, which
      have been partially attributed to its antioxidant properties. Oxidation of blood
      constituents could have a role in atherogenesis and interfere with the rheologic
      properties of the blood. In this study we investigated, whether SDH could protect
      some blood constituents against oxidative modification. In human plasma we
      measured TBARS and fluorescence generation as indicators of copper or azobis
      amidinopropane hydrochloride (AAPH) at 760 mm Hg PO2-induced lipid peroxidation.
      SDH at 50 microM inhibited copper-induced TBARS formation by 25% and fluorescence
      by 47%. SDH also inhibited AAPH-induced lipid peroxidation, but at 175 microM
      concentration only. Oxidative modification of albumine was evaluated by
      fluorescence generation. SDH at 50 microM inhibited copper/hydrogen peroxide
      fluorescence generation by 54% and at 2.5 microM it inhibited EDTA-Fe
      (II)/hydrogen peroxide fluorescence generation by 31%. The protection of albumin
      by SDH was confirmed by SDS-PAGE electrophoresis. Copper-induced red-cell lipid
      peroxidation was evaluated by TBARS formation. SDH at 250 microM inhibited copper
      induced lipid peroxidation and hemolysis by 45% and 94%, respectively. SDH also
      inhibited hemolysis in red-cell suspensions exposed to hydrogen peroxide, but not
      lipid peroxidation. Our results show that SDH may protect blood constituents from
      oxidative damage.

PMID- 9587489
TI  - [Glycosylation and lipid peroxidation in skin and in plasma in diabetic
      patients].
AB  - Glycation and free radical reactions may play a role in complications of
      diabetes. Vascular complications, as a consequence of atherosclerosis, are the
      main causes of morbidity and mortality in diabetes. The aim of this work was to
      study glycation and lipid peroxidation (LPO) in plasma and skin of type 2
      diabetic patients. The levels of advanced glycation endproducts (AGEs) in skin
      collagens are considered as the sum of accumulated glycation over time. We
      studied 20 subjects with type 2 diabetes and 20 controls. Glycated proteins were
      quantified in skin and plasma by affinity chromatography in aminophenyl boronate
      gels. AGEs were determined on skin collagen by fluorimetry. LPO was evaluated by
      fluorimetry measuring TBARS in the skin and plasma. Skin collagen-linked
      fluorescence (CLF) was higher in diabetics (p < 0.01). CLF in diabetics with
      retinopathy was higher than that of diabetics without retinopathy (p < 0.02).
      There was a positive correlation between duration of diabetes and skin CLF (p <
      0.01). TBARS were higher in skin (p < 0.01) and plasma (p < 0.001) of diabetic
      patients. We did not find any correlation between CLF and TBARS. This is not
      surprising taking into account the complexity and multifactorial aspects involved
      in LPO, while in glycation the main determinant factor is hyperglycemia.

PMID- 9587490
TI  - [Neurocristopathies: a puzzle that begins to reveal its mysteries].

PMID- 9587491
TI  - [Mutations of the endothelin-3 gene in isolated and syndromic forms of
      Hirschsprung disease].
AB  - AIMS AND METHODS: Hirschsprung's disease is a frequent congenital malformation
      regarded as a multigenic neurocristopathy. Three susceptibility genes have been
      identified in Hirschsprung's disease, namely the RET proto-oncogene, the Glial
      cell line-Derived Neurotrophic Factor and the endothelin B receptor. A total of
      174 probands with isolated Hirschsprung's disease (59 familial, 117 sporadic
      cases), and 4 patients with associated Waardenburg's syndrome and Hirschsprung's
      disease (1 familial, 3 sporadic cases) were screened for mutations in the coding
      sequence of the endothelin 3 gene. The coding sequence of the endothelin 3 gene
      was analyzed for point mutations, using a combination of SSCP analysis and direct
      DNA sequencing. RESULTS: Two heterozygous mutations (A17T and A224T) were
      identified in two patients with isolated Hirschsprung's disease. Two homozygous
      truncations mutations (E55X and GC262->T) were identified in patients with the
      Waardenburg's syndrome/Hirschsprung's disease association. CONCLUSION: The
      present data give further support to the role of the endothelin-signaling pathway
      in the development of neural crest-derived enteric neurons. They also suggest
      that either recessive and weakly penetrant dominant alleles could occur at the
      EDN3 locus, depending on the nature of the mutation.

PMID- 9587492
TI  - [Polymorphism of the microsatellites and tumor necrosis factor genes in chronic
      inflammatory bowel diseases].
AB  - OBJECTIVES: Multiplex family studies have excluded chromosome 6 as a candidate
      gene of susceptibility to inflammatory bowel disease. However, one recent study
      suggested that a gene involved in the pathogenesis of Crohn's disease is located
      on chromosome 6 confering to a microsatellite allelic combination (a2, b1, c2,
      d4, e1) a strong genetic risk factor in Crohn's disease. The aim of our study was
      to determine simultaneously the polymorphisms of the TNF microsatellites and of
      the genes coding for TNF synthesis in patients with inflammatory bowel disease.
      PATIENTS AND METHODS: Sixty patients with ulcerative colitis, 100 patients with
      Crohn's disease were compared to 64 healthy ethnically matched controls. Five TNF
      microsatellite loci (a, b, c, d, e) were typed using polymerase chain reaction
      PCR, and two dimorphisms of TNF alpha and TNF beta (intron 1) were studied by
      restriction fragment length polymorphism (RFLP). RESULTS: Allelic frequencies of
      TNF microsatellites and of TNF alpha and beta genes were similar in Crohn's
      disease, ulcerative colitis and controls. Five loci microsatellite haplotypes,
      especially a2 b1 c2 d4 e1 allelic combination, were not more frequent in Crohn's
      disease (25%) compared to ulcerative colitis (27%) or controls (20%). Subgroups
      stratification according to clinical characteristics did not modify haplotype
      frequencies. Analysis of our data taking simultaneously into account the MHC
      alleles (DRB*01 or DRB1*04) did not modify our data; however, it suggested that
      extended haplotype on short arm of chromosome 6 differed between patients and
      controls. Linkage disequilibrium (delta = -360.10(-4); P < 0.01) between a2, b1,
      c2, d4, e1 allelic combination and DRB1*04 allele was observed only in Crohn's
      disease. CONCLUSION: Percentages of patients with Crohn's disease or ulcerative
      colitis carrying TNF microsatellite or TNF alpha and beta gene haplotypes were
      similar to those of healthy controls. These data argue against involvement of the
      TNF locus without exclusion of short arm of chromosome 6 implication in Crohn's
      disease pathogenesis.

PMID- 9587493
TI  - [Intra-digestive fermentation in intestinal malabsorption syndromes: relations
      with elevated serum activity of gamma-glutamyl-transpeptidase].
AB  - The aim of this prospective study was to examine the relationship between
      gastrointestinal ethanol production ("Mei-Tei-Sho" syndrome described in Japan)
      and biological liver dysfunction associated with intestinal malabsorption
      syndromes. METHODS: Sixty-five patients with malabsorption-diarrhea underwent 98
      simultaneous measurements of plasma gamma-glutamyl-transpeptidase and of faecal
      ethanol concentrations; in 5 cases, ethanolemia and faecal ethanol concentrations
      were measured after a 250 g rice-meal; in 1, ethanol concentration was measured
      in a sample of caecal liquid in hours following local instillation of fructose
      (40 g). RESULTS: Faecal ethanol was detected at least once in 60/65 patients
      (74/98 measurements, maximum 3.50 g*L-1), more often (98.0%, P < 0.001) in 51
      patients with gamma-glutamyl-transpeptidase above 38 IU/L. Eating rice increased
      the faecal ethanol concentration in 5 patients, 2 of whom had measurable
      ethanolemia (0.20 and 0.47 g*L-1). Ileo-caecal ethanol concentration following
      local fructose instillation was 11.8 g*L-1. CONCLUSION: Endogenous
      gastrointestinal ethanol production contributes to elevated gamma-glutamyl
      transpeptidase activity observed during malabsorption syndromes.

PMID- 9587494
TI  - [Current role of endoscopic surgery techniques in benign esogastric diseases].

PMID- 9587495
TI  - [A drug for treating fulminant hepatitis?].

PMID- 9587496
TI  - [Immunobiology of tolerance of hepatic allografts: to what degree can the
      immunosuppressive treatment be avoided?].

PMID- 9587498
TI  - [Epidemiology of hepatitis C in Africa].

PMID- 9587497
TI  - [Hepatic resection and transplantation for hepatocellular carcinoma in patients
      with cirrhosis].
AB  - OBJECTIVES: Liver resection and liver transplantation are the only curative
      treatments for hepatocellular carcinoma in patients with cirrhosis. The aim of
      this retrospective study was to compare survival and tumor recurrence in patients
      with cirrhosis after hepatic resection or liver transplantation for
      hepatocellular carcinoma in patients with cirrhosis. METHODS: Between March 1988
      and March 1995, 34 patients underwent liver resection and 30 patients with
      cirrhosis had liver transplantation for hepatocellular carcinoma. The probability
      of survival and recurrence were studied according to clinical, biological and
      pathological factors, defined in liver specimens. Comparisons were performed by
      the actuarial method and log rank test. RESULTS: Five-year survival after
      resection and transplantation was 13% and 32.6%, respectively, and 5-year
      recurrence was 92.6% and 40.9%, respectively (P < 0.01). The diameter of nodules
      was a significant predictive factor of recurrence in resected patients; the
      number of nodules was a significant predictive factor in transplanted patients.
      The combination of these two factors could be used to identify two groups:
      patients with large carcinoma (diameter > 5 cm and/or number of nodules > 3), and
      patients with small carcinoma (diameter < or = 5 cm and number of nodules < or =
      3). The five-year survival rate of large hepatocellular carcinoma was 17.3% after
      resection and 0% after transplantation. The five-year survival rate of small
      hepatocellular carcinoma was 0% after resection and 69.3% after transplantation
      (P < 0.01). The five-year recurrence of large hepatocellular carcinoma was 72.3%
      after resection and 100% after transplantation. The five-year recurrence of small
      hepatocellular carcinoma was 82.6% after resection and 11.1% after
      transplantation (P < 0.01). CONCLUSIONS: Liver transplantation seems to be the
      best treatment for small hepatocellular carcinoma, mainly because of a lower
      recurrence rate. On the other hand, both treatments had a high recurrence rate in
      large hepatocellular carcinoma.

PMID- 9587499
TI  - [Liver and mucoviscidosis].

PMID- 9587500
TI  - [Severe colitis in mucoviscidosis].
AB  - We report the association of severe indeterminate colitis with cystic fibrosis in
      a 21 year old woman, with mild pulmonary involvement, and without digestive or
      pancreatic symptoms or pancreatic enzyme preparation. Ten cases of inflammatory
      bowel disease associated with a cystic fibrosis have been reported. Most fit with
      the diagnostic criteria of Crohn's disease. Although this case was compatible
      with this diagnosis, we have retained the diagnosis of "severe indeterminate
      colitis" because of the lack of specific histological features of Crohn's
      disease. The association between inflammatory bowel disease and cystic fibrosis
      is probably not fortuitous, although the pathophysiological link between the two
      diseases is unknown.

PMID- 9587501
TI  - [Hepatic transplantation for severe ductopenia related to ingestion of
      thiabendazole].
AB  - We report a case of severe cholestasis and sicca syndrome after thiabendazole
      administration for Strongyloides stercoralis infection in a 26-year-old patient.
      Liver biopsy, performed 15 days after the onset of jaundice, revealed a marked
      paucity of bile ducts, and cholestasis rapidly progressed to biliary cirrhosis.
      Because of the progression of jaundice and the development of esophageal varices,
      orthotopic liver transplantation was performed, 18 months after the beginning of
      disease. The mechanism responsible for thiabendazole-induced biliary injury is
      unknown. The association between sicca syndrome and biliary disease suggests an
      immunoallergic mechanism against an antigen which could be common to the biliary,
      lacrimal and salivary duct epithelium.

PMID- 9587502
TI  - [Proximal esophageal tuberculosis].

PMID- 9587503
TI  - [Strangulated left diaphragmatic hernia after thoracoscopy].

PMID- 9587504
TI  - [Acute colonic pseudo-obstruction in acute promyelocytic leukemia].

PMID- 9587505
TI  - [Uncommon etiology of acute pancreatitis: periarteritis nodosa].

PMID- 9587506
TI  - [Cholestatic hepatitis probably induced by clarithromycin].

PMID- 9587507
TI  - [Wegener's granulomatosis disclosed by hepato-splenic involvement].

PMID- 9587508
TI  - [Prolonged remission of chronic hepatitis C despite corticoid and
      immunosuppressive treatment].

PMID- 9587509
TI  - [Transmission of hepatitis C virus to patients from a surgeon].

PMID- 9587510
TI  - [Endoscopic treatment of "difficult" lithiasis of the common bile duct].

PMID- 9587511
TI  - [Should hypovolemia induced by paracentesis be prevented in patients with
      cirrhosis?].

PMID- 9587512
TI  - [Intra-corporeal shockwave lithotripsy in the treatment of complex lithiasis of
      the bile ducts. Comparison of endoscopic techniques and long-term results].
AB  - OBJECTIVES: About 2% of common bile duct stones and most intra-hepatic stones
      cannot be removed by conventional endoscopy. Intra-corporeal lithotripsy is an
      alternative technique for these patients. Contact lithotripsy can be obtained by
      a pulsed dye laser or by electro-hydraulic shockwaves. We compared and assessed
      the results of these two methods. METHODS: Thirty-seven patients (79 +/- 9.8
      years, 25 women and 12 men) underwent laser lithotripsy (n = 21), electro
      hydraulic lithotripsy (n = 9) or both methods consecutively (n = 7) for common
      bile duct stones (n = 31), intra-hepatic stones (n = 3) or diffuse lithiasis (n =
      3). The mean diameter of the largest stone was 23 +/- 12 mm. Lithotripsy was
      performed by a retrograde approach in 35 cases and a combined, retrograde and
      transhepatic approach in 2 cases. RESULTS: The mean number of lithotripsy
      sessions was 1.5 +/- 0.65. The overall success rate (free bile ducts with patent
      drainage) was 95%. In 2 patients, stones were not fully extracted: one underwent
      surgery, the other one was treated conservatively with antibiotics. The duration
      of the hospital stay was 9.3 +/- 4.5 days. Morbidity at 30 days was 27% and only
      one case of major morbidity (hemorrhage after sphincterotomy, 2.7%) was observed.
      There were no procedure-related mortality. Electro-hydraulic and laser groups did
      not differ significantly for success rate, morbidity and time spent at hospital.
      Follow-up information was obtained in 34 patients (91.8%) a median of 17 months
      after lithotripsy (range: 4.52 months). Ten patients died of non-biliary
      diseases. Two patients (5.8%) developed biliary symptoms 24 and 34 months after
      lithotripsy, one after unsuccessful lithotripsy. CONCLUSION: Intra-corporeal
      lithotripsy is a valuable tool for the most complex cases of duct stones, and
      with an acceptable morbidity. The results of the two techniques are similar. Late
      biliary complications after intra-corporeal lithotripsy appear to be rare.

PMID- 9587514
TI  - [Hepatotoxicity of drugs. 10th update of the bibliographic database of hepatic
      involvements and responsible drugs].

PMID- 9587513
TI  - [Contact litholysis of common bile duct calculi. Study of 44 patients].
AB  - OBJECTIVES: Endoscopic sphincterotomy has become a generally accepted method for
      extracting common bile duct stones in high risk or cholecystectomized patients.
      However, stone extraction is impossible by the usual methods in 5 to 10% of
      cases. The purpose of this study was to evaluate the effect of a recently
      developed solvent system in patients with large bile duct stones. METHODS: Forty
      four patients (15 men and 29 women, median age of years) underwent contact
      dissolution after unsuccessful Dormia extraction. Solvents were administered via
      a nasobiliary catheter in 41 patients following papillotomy and through a T-tube
      in 3 patients. Solvent mixtures (26 mM ethylene diamine tetraacetic acid, 40 mM
      sodium deoxycholate and 30% dimethyl sulfoxide in an alkaline aqueous solution;
      and a 70/30 dimethyl sulfoxide/methyl tert-butyl ether mixture) were infused
      continuously and alternatively for 2 hours. RESULTS: Bile duct stones disappeared
      in 13-24 hours of infusion in 11 patients. In 29 patients, a clear reduction in
      stone volume occurred, allowing complete endoscopic extraction of the fragments.
      In 4 patients, the size of the stone did not change. Only mild and transient side
      effects including abdominal pain (68%), nausea (72%), vomiting (52%), diarrhea
      and sleepiness (50%) were observed. CONCLUSION: Direct dissolution therapy could
      be an effective method for the non-surgical management of large bile duct stones
      in selected patients when intra- or extracorporeal lithotripsy is unsuccessful.

PMID- 9587515
TI  - [Molecular techniques in the detection of colorectal cancer].

PMID- 9587516
TI  - [Detection of protein p53 in the stool of patients with colorectal cancer].
AB  - BACKGROUND AND AIMS: Mutations of TP53, a tumor suppressor gene, are found in 60%
      to 70% of colorectal cancers. These mutations usually induce an overexpression
      caused by modification of the p53 protein conformation. The aim of this study was
      to investigate whether stool specimens of patients with colorectal cancer contain
      increased amounts of p53 protein. METHODS: p53 protein was measured using a
      sandwich enzyme immunoassay in the stool specimens of 52 patients: 25 with
      colorectal cancer, 4 with colorectal adenomas and 23 apparently free of
      gastrointestinal disease. Results were expressed as pg/mg of total protein. The
      presence of fecal occult-blood was searched using Hemoccult II and Hemolex (an
      immunochemical assay for human hemoglobin). RESULTS: Median concentrations of
      stool p53 protein were 16.6 pg/mg (range: 0-591 pg/mg) in patients with
      colorectal cancers, 39.1 pg/mg (range: 5-72 pg/mg) in patients with adenomas and
      5.9 pg/mg (range: 0-65 pg/mg) in control subjects. Resection of colorectal
      cancers caused a marked decrease of stool p53 protein concentrations. When the
      cut-off value for stool p53 protein was set at 60 pg/mg of fecal protein
      (concentrations over the 95th percentile), the positivity of the assay was
      independent of tumor size and Astler-Coller stage, but weakly associated with
      rectal location of cancer. The sensitivity of stool p53 protein for colorectal
      cancer was 44%, and the specificity was 96%. In contrast, the sensitivity of
      Hemoccult II and Hemolex tests was 48% and 44%, whereas their specificity was 91%
      and 96%, respectively. CONCLUSION: The detection of p53 protein is achievable in
      stool, but this assay is not more efficient than fecal occult blood tests for
      detection of colorectal cancer.

PMID- 9587517
TI  - [Mass screening of colorectal cancer by general practitioners in France: what is
      the real target population?].
AB  - OBJECTIVES: People at high risk of colorectal cancer, due to familial or personal
      history, or to specific symptoms, are considered not to be concerned by mass
      screening by Haemoccult test. The aim of this study was to investigate people
      aged 50 to 74 with high risk of colorectal cancer among general practitioners'
      practices in the department of Calvados (France). METHODS: A random sample of 200
      general practitioners were asked to systematically fill out a questionnaire on
      Haemoccult II proposal for 50-74 year-old patients for a whole week. RESULTS:
      Participation rate of general practitioners was 58.5%. According to our findings,
      13% of 50-74 years patients are considered not be concerned by mass screening,
      due to familial or personal history, or to specific symptoms. CONCLUSIONS:
      Colorectal cancer screening protocol have to be fit to level of risk of
      colorectal cancer. Involvement of general practitioners in colorectal cancer mass
      screening allows identification of high risk people who can then be managed with
      a more suitable screening protocol.

PMID- 9587518
TI  - [Value of rectosigmoidoscopy with bacteriological culture of colonic biopsies in
      the diagnosis of post-antibiotic hemorrhagic colitis related to Klebsiella
      oxytoca].
AB  - We report 7 cases of antibiotic-associated and hemorrhagic colitis due to
      Klebsiella oxytoca. The diagnosis was performed by sigmoidoscopy with
      bacteriological biopsy culture. PATIENTS AND METHODS: Nine patients, aged 25-83
      years, were hospitalized from February 1993 to October 1995 with hemorrhagic
      acute diarrhea following antibiotic treatment: amoxicillin (n = 3). amoxicillin
      clavulanic acid (n = 4), cephalosporine (n = 2). All patients have had two stool
      samples cultures including Clostridium difficile toxin detection. Sigmoidoscopy
      with collection of biopsy specimens for bacteriological cultures was performed
      routinely. RESULTS: Endoscopic findings established the diagnosis of colitis in
      all cases: rectitis (n = 1), diffuse left colitis (n = 4), segmental left colitis
      (n = 4). The lesions were erythematous and purpuric (n = 5) or ulcerative (n =
      4). Stool culture was normal in all cases but Klebsiella oxytoca was isolated in
      7 cases (78%). CONCLUSIONS: Sigmoidoscopy and bioptic microbiology ensured the
      diagnosis of antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca.

PMID- 9587519
TI  - [Pancreatitis and systemic diseases].

PMID- 9587520
TI  - [Hemorrhagic ascites disclosing massive Fasciola hepatica infection].
AB  - Multi-organ infection with Fasciola hepatica is uncommon. We report a case of
      severe infection with Fasciola hepatica as a cause of liver and peritoneum
      injuries with hemorrhagic ascites as well as pulmonary, pericardial, splenic and
      portal system injuries in a 37-year old man who was a native of Green Cape. The
      patient was in poor general health, had a major inflammatory syndrome, and
      polyclonal hypergammaglobulinemia (90 g/L). The diagnosis was confirmed by
      positive distomatosis serology and the presence of eggs of Fasciola hepatica in
      the histological samples of the liver and peritoneum. After treatment with
      praziquantel then triclabendazole, the global outcome was favorable.

PMID- 9587521
TI  - [Diffuse peritoneal carcinosis of pseudo-papillary and solid tumor of the
      pancreas. Role of abdominal injury].
AB  - We report the case of a young girl with diffuse peritoneal carcinomatosis due to
      pseudopapillary and solid tumor of the pancreas. Fourteen months before the
      diagnosis and treatment of the tumor, an abdominal trauma occurred. Initial
      treatment was tumor and visible peritoneal carcinomatosis resection. Eight months
      later, relapse of peritoneal carcinomatosis occurred and the patient was
      reoperated. All macroscopic lesions were removed. Thirty-seven months after first
      laparotomy, the patient was well but abdominal ultrasound led to suspicion of
      hepatic metastasis. Among 17 published cases of metastatic pseudopapillary and
      solid tumor of the pancreas (including 6 cases with peritoneal carcinomatosis),
      trauma was described in 11 cases (including 3 cases with peritoneal
      carcinomatosis). Pseudopapillary and solid tumor of the pancreas may spread
      outside the pancreas, particularly in peritoneal cavity. Metastatic spread may be
      promoted by trauma, including tumor biopsies which should never be performed.

PMID- 9587523
TI  - [Acute hepatitis asociated with ingestion of of diacerein].

PMID- 9587522
TI  - [Hyperthyroidism: an uncommon cause of jaundice].

PMID- 9587524
TI  - [Should patients with cirrhosis be subjected to biopsy of the kidney?].

PMID- 9587525
TI  - [Suicide in a patient with chronic viral hepatitis C treated with interferon
      alpha: favoring role of alcohol?].

PMID- 9587526
TI  - [Treatment of duodenal tumor stenosis by endoscopic implantation of an expansible
      metal stent].

PMID- 9587527
TI  - [Postoperative duodeno-ileal stenosis: efficacy of a metal stent].

PMID- 9587528
TI  - [Large colonic arteriovenous malformation in a young patient].

PMID- 9587529
TI  - [Cytomegalovirus ulcerative and hemorrhagic rectitis in an immunocompetent
      patient].

PMID- 9587530
TI  - [Digestive and nutritional changes induced by Ramadan fasting. Methodological
      requirements and pertinence of scientific observations].

PMID- 9587531
TI  - [Effect of Ramadan fasting on intragastric pH recorded during 24 hours in healthy
      subjects].
AB  - OBJECTIVES: Lifestyle changes during Ramadan as the meals are taken exclusively
      in the evening, and nightly sleep is often delayed and shortened. The wake/sleep
      cycle is also modified. The aim of this study was to evaluate the influence of
      Ramadan on gastric acidity in healthy volunteers. METHODS: Nine healthy
      volunteers had 24-hour measurement of the gastric pH; 4 periods were compared:
      one week prior to Ramadan, day 10 and day 24 during Ramadan, and one month after
      Ramadan. The pH profiles and the [H+] activity (area under the curve) were
      measured during 24 hours, the night phase (5PM-8AM) and diurnal phase (8AM-5PM).
      RESULTS: The diurnal variations of the pH profile were more significant; the
      median pH was 2.3 prior to Ramadan, 1 at day 10 and day 24 and 1.6 one month
      after Ramadan. The 24-hours [H+] activity increased by 45% at day 10 of Ramadan
      compared with its level prior to Ramadan. This increase was mostly diurnal
      (+122%) and also nightly (+25%). The activity [H+] was steady during Ramadan. One
      month after Ramadan, the 24-hours [H+] activity was 23% higher than the one noted
      before Ramadan. CONCLUSIONS: This study shows that the conditions of feeding
      imposed by Ramadan are associated with an increase of the gastric acidity mainly
      in diurnal phase. These results do not explain the origin of the healthy
      volunteer digestive symptoms encountered during Ramadan.

PMID- 9587532
TI  - [Effect of the observance of diurnal fast of Ramadan on duodenal ulcer healing
      with lansoprazole. Results of a prospective controlled study].
AB  - OBJECTIVES: The aims of this study were: a) to determine whether patients with
      duodenal ulcer treated with a proton pump inhibitor may fast during the month of
      Ramadan, b) to evaluate the result of the treatment in this condition. METHODS:
      Fifty-seven patients with acute duodenal ulcer confirmed by endoscopy were
      included in the study. All the patients received 30 mg lansoprazole per day
      during 4 weeks. After randomization, patients of group I (n = 27) were dispensed
      from fasting, while those of group II (n = 30) fasted. Endoscopy was performed at
      the end of the month of the fast. RESULTS: The course of symptoms was not
      different in groups I and II. There were no ulcer complications. Healing rates at
      endoscopy were 88.8% and 90% in groups I and II, respectively. Fasting had no
      influence on the result of duodenal ulcer treatment by lansoprazole which was
      well tolerated. CONCLUSION: Patients with duodenal ulcer treated with
      lansoprazole may fast without running any risk.

PMID- 9587533
TI  - [Total duodenal diversion in the treatment of complex peptic esophagitis].
AB  - AIMS OF THE STUDY: The aims of this study was to report the results of total
      duodenal diversion in patients with complex peptic esophagitis (peptic stenosis,
      acquired short esophagus, columnar lined esophagus, previous surgery). PATIENTS
      METHODS: Total duodenal diversion has been performed in 107 patients with complex
      peptic esophagitis. The standard procedure--including a troncular vagotomy, an
      antrectomy and a 70 cm Roux-en-Y gastro-jejunostomy--was used in 68 cases (64%).
      Technical adjustments were necessary in the 39 others patients. RESULTS: Two
      patients (1.8%) died postoperatively. Permanent healing of esophagitis was
      observed within 3 months in 88% of patients. Esophagitis healed in all patients
      operated with the standard technique. Three hours postprandial pH-monitoring was
      normal postoperatively in 92% of patients. Four anastomotic ulcers occurred in
      patients who did not have vagotomy. Among patients with columnar lined esophagus,
      one complete and six partial regressions were observed; no malignant degeneration
      was observed with a 210-patient-year follow-up. Among the 39 peptic stenoses, all
      except one (2.6%) resolved. Functional disorders occurred in 27% of patients
      within the first postoperative months; these disorders persisted in 14% of
      patients (Visick III or IV) after 3 years. The main disorders (dumping syndrome,
      anastomotic ulcer, diarrhea) were observed when a two-thirds distal gastrectomy
      has been performed to avoid the dangerous completion of vagotomy after a previous
      Heller's myotomy. CONCLUSION: These results suggest that total duodenal diversion
      is a suitable treatment of complex peptic esophagitis.

PMID- 9587534
TI  - [Cellular adherence and chronic inflammatory bowel diseases].

PMID- 9587535
TI  - [Effects and risks of prolonged antiviral treatments: the example of chronic
      hepatitis B].

PMID- 9587537
TI  - [Acute inoperable cholecystitis treated by endoscopic naso-vesicular drainage.
      Study of 15 patients].
AB  - OBJECTIVES: Cystic duct cannulation during endoscopic retrograde cholangiography
      is now possible, due to advances in endoscopic equipment and methodology. The aim
      of this study was to assess the role of endoscopic transpapillary cholecystostomy
      in inoperable patients with acute cholecystitis. METHODS: Between October 1993
      and February 1996, cystic duct cannulation was performed in 15 patients with
      acute cholecystitis (9 men and 6 women; mean age 74.8 years. Acute calculous
      cholecystitis was associated with cholangitis in 4 cases, with pancreatitis in 2
      cases, and with perforation of the gallbladder in 1 case. RESULTS: Cystic duct
      cannulation was successful in 13 patients (86.6%), and resulted in remission of
      cholecystitis by nasovesicular drainage associated with antibiotherapy in all
      cases. No morbidity and mortality due to this method was observed at one month.
      No recurrence was observed after a mean follow-up of 8 months (range: 6 weeks-14
      months). CONCLUSION: This study suggests that endoscopic nasovesicular drainage
      is a good alternative treatment to percutaneous cholecystostomy in inoperable
      patients.

PMID- 9587536
TI  - [Comparison of immunogenicity of vaccination and serovaccination against
      hepatitis B virus in patients with alcoholic cirrhosis].
AB  - OBJECTIVES: The association of anti-HBs immunoglobulins and anti-HBV vaccine
      could increase the immunogenicity of the latter. The aim of this prospective
      randomized trial was to compare the immunogenicity of anti-HBs vaccination and
      serovaccination in alcoholic patients with cirrhosis. METHODS: Alcoholic patients
      with cirrhosis were randomized in 2 groups: a) Vaccination group: 3 i.m.
      injections of GenHevac B followed by one booster at month 9; b) Serovaccination
      group: same vaccination schedule followed by one i.m. injection of anti-HBs
      immunoglobulins (500 IU). RESULTS: Twenty-five patients (17 males and 8 females,
      mean age 56 years) were included in the study: 13 received a vaccination and 12
      received a serovaccination. After 12 months, the seroconversion rates were 69%
      and 67% in vaccination and in serovaccination groups, respectively. The
      predictive factors of non responsiveness were as following: Child B cirrhosis,
      low number of CD8, a high CD4/CD8 rate, the existence of HLA DR7 antigen, and the
      absence of HLA DR1 antigen. CONCLUSION: In alcoholic patients with cirrhosis,
      serovaccination does not increase the immunogenicity of anti-HBs vaccination and
      should not be recommended.

PMID- 9587539
TI  - [Stellate cells of the liver and hepatic fibrogenesis].

PMID- 9587538
TI  - [Contrast media in magnetic resonance imaging of the liver].

PMID- 9587540
TI  - [Pancreatoblastoma in adults].
AB  - Pancreatoblastoma is a rare pancreatic tumor, which usually occurs during
      childhood. We describe here the ninth adult case in a 21-year-old woman, who died
      7 months after diagnosis despite complete surgical resection and adjuvant
      chemotherapy. Pancreatoblastoma in adults has a poor prognosis, at variance with
      what may be observed in childhood.

PMID- 9587541
TI  - Extensive ulcerative colitis and extraintestinal manifestations in a patient with
      HIV infection and significant CD4 T-cell lymphopenia.
AB  - We report a heterosexual patient with HIV infection and a CD4 T-cell count of
      0.45 x 10(9)/L who developed mild ulcerative proctitis, sacroileitis and
      oligoarthiritis. While he was treated with 5-aminosalicylic enemas, the patient
      rapidly developed severe pancolitis. An emergency colectomy without procetectomy
      was performed. A few months later, he suffered recurrence of ulcerative
      proctitis, aggravation of arthritic pain and developed anterior uveitis. All
      symptoms disappeared after proctectomy. There was no evidence for opportunistic
      infection or Kaposi's sarcoma. Antineutrophil cytoplasmic antibodies were
      positive and the HLA-B27 antigen was present. CD4 counts were lower during the
      phases of active disease than during remission. This case demonstrates that
      severe ulcerative colitis can occur in the presence of moderate T-cell defects.
      In view of a recent report of remission of Crohn's disease under comparable
      circumstances, it is possible that the extent of T-cell involvement in both
      diseases is radically different.

PMID- 9587542
TI  - [Radiological aspects of hepatic tuberculoma. 3 cases].
AB  - Localized macronodular tuberculosis of the liver is rare. Tuberculous involvement
      of the liver is usually a diffuse process. We report 3 cases in which clinical
      and imaging features suggested the diagnosis of macronodular hepatic tuberculoma
      which was pathologically confirmed by percutaneous biopsy. In the first case,
      abdominal CT-scan showed a noncalcified hypodense nodular lesion in segment IV of
      the liver with an enhancing peripheral rim. In the second case, ultrasound showed
      4 homogenous hypoechoic hepatic nodules. In the third case, a nodule was
      incidentally identified in segment VII of the liver. The lesion was hypoechoic
      with ultrasound, hypodense without enhancement on CT-scan, and hyperintense on
      both T1- and T2-weighted MR imaging. After percutaneous biopsy, pathologic
      examination showed peripheral granulomous lesions in all patients with central
      caseous necrosis consistent with tuberculosis in two patients despite a negative
      for Zielh stain. Specific M. tuberculosis culture was positive in the first
      patient, negative in the second patient, and was not performed in the third
      patient. Appropriate treatment resulted in disappearance of hepatic lesions on
      follow-up imaging examinations. These 3 cases show that clinical and imaging
      features of hepatic tuberculoma are not specific and that percutaneous biopsy of
      lesions provides a definite diagnosis.

PMID- 9587544
TI  - [Improvement of dysphagia with motor disorders after stopping neuroleptic
      treatment].

PMID- 9587543
TI  - [Gastric amyloidosis in simulating a pseudotumor].

PMID- 9587545
TI  - [Right sigmoid-popliteal fistula in diverticular disease].

PMID- 9587546
TI  - [Every communicating cyst developed on chronic pancreatitis may not be always a
      common cyst].

PMID- 9587547
TI  - [Vaginal metastasis disclosing rectal adenocarcinoma].

PMID- 9587548
TI  - [Vaccination against hepatitis A of children living in highly endemic area].

PMID- 9587549
TI  - [Convulsive seizure during a treatment with interferon alpha for chronic viral
      hepatitis C].

PMID- 9587550
TI  - [Congenital high increase of serum alpha-fetoprotein: case of a family].

PMID- 9587551
TI  - [Hepatic metastasis after excision of invasive thymoma: mode of manifestation of
      a 2nd asymptomatic tumor of colonic origin].

PMID- 9587552
TI  - [Oral contraceptives and benign tumors of the liver].

PMID- 9587553
TI  - [Should benign tumors of the liver be followed-up, and how?].

PMID- 9587554
TI  - [Acute thrombosis of the portal system. Treatment with alteplase and heparin or
      with heparin alone in 10 patients].
AB  - OBJECTIVES: We report the efficacy of alteplase (a recombinant tissue plasminogen
      activator) with heparin or heparin alone in the treatment of acute thrombosis of
      the portal venous system. METHODS: Ten consecutive patients with acute portal
      venous system thrombosis were studied. Five patients were treated with alteplase
      and heparin, and the remaining 5 patients, who were asymptomatic or had a
      contraindication to alteplase, were treated with heparin alone. RESULTS: In 3 of
      the 5 patients treated with alteplase, ultrasonography showed total resolution of
      the thrombus; the remaining 2 had partial resolution of the thrombus. In 4 of the
      5 patients treated with heparin alone, ultrasonography showed total resolution of
      the thrombus, and no change in one. No bleeding occurred. CONCLUSION: Treatment
      with heparin can result in complete recanalisation of acute portal venous system
      thrombosis. These data suggest that combined therapy with systemic alteplase does
      not increase the efficacy of heparin.

PMID- 9587555
TI  - [Value of high-dose interferon-alpha in chronic viral hepatitis C patients non
      responder to a 1st treatment. Pilot study prospective and randomized trial].
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of two different
      doses of alpha interferon (IFN) for retreatment in chronic hepatitis C patients
      who were non responders to initial treatment by IFN at a dose of 3 MIU TIW for 6
      months. METHODS: This open, pilot, prospective, randomized and bicentric study
      included patients with biopsy-proven chronic hepatitis C. Non response was
      defined as serum ALT levels > 2 upper limit of normal for the entire first
      treatment period, HCV RNA positivity by PCR at the end of the first treatment
      period, and the persistence of histologically-proven chronic active hepatitis
      after the first treatment period. Patients were randomized into two groups: group
      I received IFN alpha 2b 10 MIU TIW for 2 months, then 6 MIU TIW for 4 months,
      group 2 received IFN alpha 2b 6 MIU TIW for 6 months. RESULTS: Twenty three
      patients (17 male, 6 female, mean age: 38.7 +/- 9.1 years) were included: 14 were
      randomized in group 1 and 9 in group 2. Both groups were similar for the main
      clinical, biochemical, and histological variables. At the end of retreatment, 2
      patients (14.2%) had biochemical and virological response in group 1 and 4 in
      group 2 (44.4%) (non significant). Only one biochemical and virological sustained
      response was observed in group 2 (11.1%) (non significant). There was no
      difference between the groups for complete and sustained response. An overall
      statistical significant improvement of Knodell score was observed (7.8 +/- 3.8 vs
      9.6 +/- 3.2, P < 0.02) in the 18 patients who had a second biopsy 6 months after
      the end of therapy, while the Knodell score did not change at the end of the
      first treatment period. This improvement was statistically significant in group 2
      (5.4 +/- 3.0 vs 9.2 +/- 9.5 before treatment, P < 0.02) and concerned
      intralobular necrosis (P < 0.05). The Metavir index did not change. The number of
      side-effects was similar in both groups. CONCLUSIONS: These results suggest that
      histological improvement may be obtained after IFN retreatment in some patients
      who are non-responders to the first treatment, despite an absence of biochemical
      and/or virological response.

PMID- 9587557
TI  - [Indications and results of hepatic transplantation in adults].

PMID- 9587556
TI  - [Focal nodular hyperplasia and hepatocellular adenoma in women. Current data].

PMID- 9587558
TI  - [Endoscopic treatment of Zenker's diverticulum using CO2 laser. 17 cases].
AB  - OBJECTIVES: Various treatment regimens have been used for the management of
      Zenker's diverticulum. These include surgery (transcervical diverticulectomy,
      myotomy) and endoscopic treatment with rigid instruments or flexible endoscope.
      The aim of this study is to report the results of the treatment of Zenker's
      diverticulum with rigid endoscope applied CO2 laser and to compare them with
      other types of treatment. PATIENTS AND METHODS: Between May 1991 and November
      1996, 17 patients (8 males, 9 females) with symptomatic Zenker's diverticulum
      underwent endoscopic treatment under short general anesthesia applied CO2 laser.
      The mean age of the patients was 73.2 years (range: 54 to 97 yrs). All patients
      had significant symptoms such as dysphagia (15 patients out of 17). All patients
      were clinically evaluated after the procedure. RESULTS: The endoscopic incision
      was performed in one session per patient. Symptoms and dysphagia disappeared in
      all patients except one (dysphagia). Two complications (one cervical emphysema,
      one fistula) were managed clinically. Mortality was 0%. Mean follow-up was 17
      months. There was no recurrence of dysphagia, all patients remained asymptomatic.
      CONCLUSIONS: Rigid endoscopic treatment of symptomatic Zenker's diverticulum
      applied with laser CO2 is an efficient and safe method. It should be considered
      as an alternative therapy for Zenker's diverticulum, especially for patients at a
      high surgical risk.

PMID- 9587559
TI  - [Colorectal adenocarcinoma in patients under 40 years of age].
AB  - OBJECTIVES: The aim of this study was to assess prognosis and treatment of
      colorectal cancer in young adults. METHODS: In a retrospective review of 1,917
      patients with colorectal cancer, 80 patients were under the age of 40 years
      (4.2%). RESULTS: The mean follow-up was 5.2 years (range: 0-16 years). There was
      a family history of colorectal cancer in 20% of the patients, either familial
      adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC
      syndrome). Five prognostic factors for the 10 year survival rate were found:
      stage of tumor in the Astler-Coller classification (A, B1-2, C1-2 and D, 100, 75,
      38 and 11% respectively), tumor vascular invasion (16%), poorly differentiated
      tumors (30%), emergency surgery (21%) and non curative resections (5%). The colon
      recurrence rate at 8 years was 14% in the case of HNPCC syndrome. The recurrence
      rate for patients with neither FAP nor HNPCC syndrome was 11.5% at 8 years and
      for patients alive at 1 year was 16.5%. CONCLUSIONS: In patients under the age of
      40 years, a subtotal colectomy, even as a second operation should be considered,
      if the prognostic factors are favorable. A genetic analysis seems to be essential
      in the management of these patients.

PMID- 9587561
TI  - [Duodenal polyposis in familial adenomatous polyposis: what are the risks and ho
      to manage them?].

PMID- 9587560
TI  - [Stimulation of ileal transport of calcium by sorbitol in in situ perfused loop
      in rats].
AB  - OBJECTIVES: The aim of this study was to study the effect of sorbitol on sodium,
      water and calcium fluxes in rat ileum in situ perfused loop. METHODS: Net water,
      sodium and calcium fluxes, and one-way calcium fluxes were measured in situ in a
      perfused rat ileal loop in the presence of varying concentrations of sorbital.
      RESULTS: High concentrations of sorbitol in perfused ileal solution induced a
      decrease of sodium and water fluxes and a concomitant increase of lumen to mucosa
      calcium flux associated with an increase of net calcium flux, using a solution
      containing either 8.0 or 1.25 mM calcium. These effects were independent of
      absolute initial values of water and sodium fluxes. They were observed in the
      presence of 25 mM glucose, 10 mM theophyllin or after treatment of rats with
      dexamethasone. CONCLUSION: These effects of sorbitol on calcium flux are not
      compatible with a stimulation of paracellular pathway. By contrast, they can be
      explained by a stimulation of transcellular calcium pathway in ileum associated
      with the hyperpolarisation of the cells induced by the decrease of luminal sodium
      concentration necessary in the presence of sorbitol to maintain unchanged
      osmolarity of perfusate.

PMID- 9587562
TI  - [Lactic acidosis and hepatic mitochondrial changes during a treatment with
      zidovudine].
AB  - Adverse effects of zidovudine, which mainly result in myopathies and
      hematological disorders, could be due to multitissular mitochondrial toxicity of
      the drug. During zidovudine treatment, most cases of lactic acidosis have been
      attributed to mitochondrial myopathy. We report a case of hepatocellular failure
      with lactic acidosis in a 33 year-old patient with the human immunodeficiency
      virus infection and treated with zidovudine for 8 months. Liver biopsy showed
      massive macrovacuolar steatosis and ultrastructural mitochondrial abnormalities
      similar to those previously described in the skeletal muscle. This is the second
      reported case of lactic acidosis and hepatocellular failure which is probably
      related to hepatic mitochondrial dysfunction caused by zidovudine.

PMID- 9587564
TI  - [Radiation-induced esophageal cancer. Presentation of a case and review of the
      literature].
AB  - Esophageal cancer induced by radiation is uncommon. Irradiation of the head, the
      neck, the chest and the abdomen may cause an esophageal cancer several years
      later. Therefore, regular gastroscopy and biopsy of esophageal mucosa are
      strongly recommended in symptomatic patients. Surgery combined or not with
      radiotherapy seems to be the most effective treatment for this kind of cancer. We
      report a case of squamous cell carcinoma of the esophagus diagnosed 13 years
      after chemotherapy and radiotherapy for Hodgkin disease stade IIIb.

PMID- 9587563
TI  - [Favorable course of hepatitis B virus reactivation with hepatocellular
      insufficiency by a treatment combining corticoids, foscarnet and ganciclovir].
AB  - Reactivation of hepatitis B virus replication is a rare event during the natural
      history of chronic hepatitis B. However, the clinical presentation may be severe
      and an effective therapeutic protocol must be established. We report a case of
      spontaneous reactivation of hepatitis B virus infection with liver failure. For
      the moment, no medical treatment has been defined in this situation. A
      combination of corticosteroids and antiviral drugs (foscarnet and ganciclovir)
      resulted in clinical and biological recovery, and HBV elimination. If the
      efficacy of this combined treatment is confirmed in a larger population, this new
      physiopathological approach should be considered whenever life threatening liver
      failure occurs.

PMID- 9587565
TI  - [Pseudotumor nodular lymphoid hyperplasia of the ileum].
AB  - We report a case of pseudotumoral nodular lymphoid hyperplasia of the ileum in an
      immunocompetent 62-year-old woman. Ileoscopy showed multiple voluminous, soft,
      pliable, polypoid ileal lesions. Perendoscopic biopsies revealed a florid
      inflammation of the mucosa, characterised by numerous enlarged follicles with
      well-developed reactive germinal centres separated by a mixed infiltrate of
      lymphocytes, plasma cells and eosinophils. Immunohistochemistry showed a
      polytypic staining for kappa and lambda light-chains in the follicles and between
      and confirmed the reactive nature of the infiltrate. CT scan of the abdomen
      disclosed large periileal lymph nodes and a right ileocolectomy was performed.
      Twelve cases of pseudotumoral nodular lymphoid hyperplasia of the ileum have been
      reported in the literature in patients older than 25. In all cases, the diagnosis
      was performed after laparotomy. As shown in our case report, the diagnosis is
      possible on multiple perendoscopic biopsies.

PMID- 9587566
TI  - [Reversible acute pandysautomia and association with aorto-mesenteric
      constriction syndrome?].

PMID- 9587568
TI  - [Disappearance of serum autoantibodies during treatment with interferon alpha in
      a patient with chronic hepatitis C].

PMID- 9587567
TI  - [Efficacy of lamivudine on the replication of hepatitis B virus in a patient with
      acquired immunodeficiency syndrome].

PMID- 9587569
TI  - [Volvulus of the gallbladder: a difficult diagnosis requiring urgent operation].

PMID- 9587570
TI  - [Pseudo-achalasia secondary to esophageal amyloidosis treated by pneumatic
      dilatation].

PMID- 9587571
TI  - [Idiopathic ileo-colonic invagination in adults. Presentation of a case of
      functional origin].

PMID- 9587572
TI  - [Acute biliary pancreatitis complicated by hemolytic-uremic syndrome].

PMID- 9587574
TI  - [Familial macular dystrophy of polymorphic aspect associated with optic nerve
      drusen].

PMID- 9587573
TI  - [High-dose furosemide: a new cause of chronic pancreatitis?].

PMID- 9587576
TI  - [Color Doppler ultrasonography in retinitis pigmentosa. Preliminary study].
AB  - PURPOSE: Retinitis pigmentosa is a bilateral retinal degeneration. The primary
      disorder is still debated. METHODS: We performed a prospective investigation of
      the ocular circulation directly by color Doppler imaging (CDI). A total of 28
      eyes of 14 patients (8 men and 6 women, affected with retinitis pigmentosa) were
      recruited for this study. For each case were evaluated protosystolic velocity and
      the resistive index of the ophthalmic artery, central retinal artery, posterior
      ciliary arteries and choroid. These values, furthermore, have been compared with
      a control group. RESULTS: The results of the CDI in the group of RP and in the CG
      were: in the OA: PSV 31.177 +/- 5.119 cm/sec vs 36.700 +/- 3.152 cm/sec (p <
      0.007); RI 0.713 +/- 0.058 vs 0.717 +/- 0.019 (p < 0.0839); in the CRA PSV 7.075
      +/- 1.611 cm/sec vs 12.710 +/- 2.795 cm/sec (p < 0.001); RI 0.560 +/- 0.062 vs
      0.550 +/- 0.051 (p < 0.234); in the PCA: PSV 8.569 +/- 3.408 cm/sec vs 14.100 +/-
      2.571 cm/sec (p < 0.001) with RI 0.634 +/- 0.090 vs 0.681 +/- 0.045 (p < 0.145).
      In the CHO: PSV 12.312 +/- 2.327 cm/sec vs 16.170 +/- 1.846 cm/sec (p < 0.001)
      with RI 0.581 +/- 0.072 vs 0.638 +/- 0.050 (p < 0.065). CONCLUSION: Our results
      suggest that in the affected eyes there is a statistically significant reduction
      in blood flow in ophthalmic and ciliary arteries. These data offer new views on
      the retinitis cause of pigmentosa and possible therapeutics to be studied.

PMID- 9587575
TI  - [Retinal involvement in drepanocytosis in Togo. Correlation between age, genotype
      and retinopathy].
AB  - PURPOSE: To evaluate different retinal complications, study correlation with age
      and links with genotypic forms in Togolese sickle cell patients. MATERIAL AND
      METHOD: Patients were recruited between 1994 and 1996 at the hospital, genotypic
      diagnosis by electrophoresis, systematic angiofluorography were performed and
      laser photocoagulation of retinal neovascularisation if needed. RESULTS: A total
      number of 190 patients were recruited, 84 (44.21%) had retinopathy, while 106
      (55.79%) were normal. The SC form was most affected with 50 patients (26.3%),
      followed by the SS group in 11.05% (21 patients), and AS trait, 2.65% (5
      patients). Patients most affected by proliferative retinopathy were aged 35-44
      years (n = 30; 15%), 25-34 years in 23.8% and 15-24 years in 20.6%. CONCLUSION:
      Young Togolese sickle cell patients aged 35 to 44 year-old and the SC forms
      appear to have a relative high risk of proliferative retinopathy in this study.

PMID- 9587577
TI  - [Immunolabelling of collagen types I, III and IV, laminin and fibronectin in the
      human lens capsule].
AB  - PURPOSE: To localize collagen types I, III, and IV, laminin and fibronectin in
      the anterior human lens capsule. MATERIAL AND METHODS: Twenty-one anterior
      capsules were sampled by capsulorhexis during extracapsular cataract extraction
      (mean age 71.5). All capsules were labelled by an immunostaining specific for
      each antibodies. Immunostaining of four capsules was revealed with
      immunoperoxydase and seventeen using indirect immunofluorescence. RESULTS:
      Labelling of collagen types I and III was observed throughout the entire
      thickness of the capsule for each technique, the strongest labelling was found in
      the base of the epithelial cells with immunofluorescence. Collagen type IV was
      observed at the base of the epithelial cells whichever technique was used.
      Laminin could be detected in the inner layer of the capsule, using
      immunoperoxydase or immunofluorescence. No specific labelling was found for
      fibronectin using the two techniques. CONCLUSIONS: Different kinds of collagens
      have been found in capsules, more particularly the type III. The latter does not
      appear on other ocular basement membrane. Because of this uneven distribution in
      the capsule's thickness, each collagen might have a specific function.

PMID- 9587578
TI  - [Choice of the site of incision for cataract surgery without suture according to
      preoperative astigmatism].
AB  - PURPOSE: To compare surgically induced astigmatism, postoperative astigmatism and
      uncorrected visual acuity after cataract surgery depending on the site of a 4 mm
      sutureless incision (superior scleral or corneal temporal) and on the
      preoperative astigmatism. METHODS: According to preoperative astigmatism and to
      the site of incision 4 groups have been distinguished. Group I: with-the-rule
      preoperative astigmatism and superior scleral incision, group II: with-the-rule
      preoperative astigmatism and corneal temporal incision, group III: against-the
      rule preoperative astigmatism and superior scleral incision, group IV: against
      the-rule preoperative astigmatism and temporal incision. The patients had a
      preoperative and postoperative (Day 1, 8, 30, 180, 360) keratometry. Surgically
      induced astigmatism, preoperative and postoperative astigmatism have been
      expressed according to Naeser method. The uncorrected visual acuity at Day 30 has
      been compared in each group. RESULTS: Preoperative astigmatism was similar in the
      four groups. Surgically induced astigmatism was -0.18 diopter (D) at day 30 and 
      0.41 D at day 360 for the scleral incisions and +0.60 D at day 30 and +0.33 D at
      day 360 for the temporal incisions. The postoperative astigmatism was +0.5 D at
      day 30 and +0.27 at day 360 for the group I and +1.22 D at day 30 and +0.95 D at
      day 360 for group II. There was no statistical difference in the uncorrected
      visual acuity. Postoperative astigmatism was -0.8 D at day 30 and -1.03 D at day
      360 in group III and -0.04 D at day 30 and -0.31 D at day 360 in group IV. The
      visual acuity was significantly better in group IV than in group III. CONCLUSION:
      In cases of preoperative with-the-rule astigmatism < or = 0.75 D the two sites of
      incisions are possible. In cases of WTR astigmatism over 0.75 D we perform a
      superior scleral approach. In cases of against-the-rule astigmatism the temporal
      incision is the only one to consider.

PMID- 9587579
TI  - [Astigmatism after penetrating keratoplasty. Videokeratoscopic analysis on a
      series of 60 grafts].
AB  - PURPOSE: To study the factors which induce post keratoplasty astigmatism. To
      assess the reliability of different methods in the astigmatism measurement and to
      study the visual acuity predicting factors. METHODS: We retrospectively studied
      the corneal topography in 60 eyes with penetrating keratoplasty after suture
      removal, using the CAS* (Eye Sys). The diagnosis was keratoconus in 65% of the
      cases and bullous keratopathy in 15% of the cases. The graft was secured with a
      single running suture in 38.3% of the cases, interrupted sutures in 23.3% of the
      cases, or a combination of both running and interrupted sutures in remaining
      28.3%. RESULTS: The suture method, diagnosis and surgeon did not influence
      subjective refraction nor visual acuity. The topographic pattern correlated with
      subjective cylinder (rs = 0.52 p = 0.02). The refractive power cylinder
      ("Holladay diagnostic summary") correlated well with subjective cylinder (rs =
      0.81 p < 0.001) and visual acuity (rs = -0.63; p < 0.001). The Javal keratometry
      remains the best method to measure astigmatism axis (rs = 0.58; p < 0.001).
      CONCLUSIONS: The Holladay diagnostic summary (refractive power) is a useful tool
      for evaluating qualitative outcome of corneal transplantation.

PMID- 9587580
TI  - [Cryptococcal chorioretinitis and acquired immunodeficiency syndrome].
AB  - We report a case of cryptococcal chorioretinitis discovered at ophthalmological
      examination of a 68-year-old woman with acquired immune deficiency syndrome. This
      localization revealed cryptococcal septicemia, without involvement of the central
      nervous system unlike most cases reported. Therapy with fluconazole (400 mg per
      day) led to gradual regression of the chorioretinal lesion.

PMID- 9587581
TI  - [Malignant non-Hodgkin lymphoma of the central nervous system with ocular site.
      Value of vitrectomy for diagnosis].
AB  - Diagnosis of intraocular lymphoma is difficult and should be considered in middle
      aged or older patients with a chronic uveitis. Many explorations (lumbar
      punctures, brain imaging and vitrectomies) may be needed before correct diagnosis
      is made. We report the case of a 50-year-old woman with an intraocular lymphoma
      for whom the diagnosis was confirmed by a vitrectomy.

PMID- 9587582
TI  - [Ring recurrence of ciliary body melanoma after proton-beam therapy].
AB  - A malignant ciliary body melanoma was treated by proton-beam irradiation. Ring
      shaped recurrence with extraocular extension appeared thirty-six months later and
      required enucleation. Histologic study revealed a predominant epithelioid cell
      type tumor, flattened in previously treated area. Proton-beam irradiation
      efficiency depends on clinical evaluation, which remains questioned in ciliary
      body locations where circumferential extension could be misevaluated.

PMID- 9587583
TI  - [Triple procedure with phacoemulsification prior to grafting].
AB  - We report a surgical technique which combines phacoemulsification and posterior
      chamber in the bag intra-ocular lens implantation before penetrating
      keratoplasty. This combined technique can only be performed in eyes with clear
      cornea. This technique seems to be safer during cataract extraction. We compared
      this combined procedure with the classical technique which associates manual
      extracapsular extraction and posterior chamber intra-ocular lens implantation and
      penetrating keratoplasty.

PMID- 9587584
TI  - [Apoptosis and the eye. Review of the literature].

PMID- 9587585
TI  - [Retinal detachment secondary to CMV retinitis].

PMID- 9587586
TI  - [Patient information and preoperative informed consent: comments on an
      experience].
AB  - We gave consideration to the new legal obligation to a medical doctor to prove
      that he has given to a patient adequate information. 312 cases of cataract or
      glaucoma received written information about their disease and the risks of
      surgery. An informed consent regarding the operation and the post-operative care
      were signed by all patients. Information cover surgical risks, sides effects,
      unpredictable events, care steps and all last minute protocol modifications.
      These documents were given when scheduling the surgery. No cancellation and no
      objection were noticed. The French Code Civil article 1315 was not dedicated to
      medical exercise but it concerns physicians. The way to give a proof is not
      clear. Nothing is asked in the by-laws and every medical doctor can choose the
      method he prefers. A signature is not an obligation and an informed consent is
      not an authorization. A discussion is opened to clear the best and safest
      recommendations to obtain a legal proof of information. Now, written texts seem
      to be the easiest procedure. Quality medical records and personal relation
      between patient and surgeon are of great importance to prevent patient
      unsatisfaction and disappointment.

PMID- 9587587
TI  - [Surgical treatment of serous detachments of the macular neuroepithelium in
      diabetics].
AB  - PURPOSE: Maculopathy in diabetes mellitus represents one of the most serious
      complications of the diabetic retinopathy. Retinal photocoagulations are often
      impossible and even dangerous. We propose a new method of surgical treatment for
      this macular serous detachment. MATERIAL AND METHOD: Thirteen eyes from 11
      patients were treated using the same surgical procedure: vitrectomy, aspiration
      of subretinal liquid through a temporal retinotomy, fragmentation and extraction
      of the sub and intra retinal exsudates through one or several retinotomies,
      macular massaging with fluorodecaline, endophotocoagulations (focal on vascular
      anomalies and macular grid) and fluid-gas exchange (C3F8). RESULTS: Macular
      serous detachment and subretinal exsudates disappeared in all the cases, the
      fluorescein leakage decreased. A functional improvement was obtained in 11 eyes,
      a stabilization in 2. DISCUSSION: The clinical results of this new surgical
      treatment appear to depend on the preoperative macular ischemia and on the age of
      the detachment. This surgical procedure is very beneficial but could perhaps be
      technically improved.

PMID- 9587588
TI  - [Toxoplasmic chorioretinitis complicated by retinal detachment].
AB  - PURPOSE: To describe and analyse relationship between chorioretinal toxoplasmosis
      and retinal detachment. PATIENTS AND METHODS: Seven immunocompetent patients
      examined and treated between November 1992 and March 1996, with ocular
      toxoplasmic retinochoroiditis and retinal detachment. RESULTS: Of the 7 patients
      examined, 5 had active retinochoroiditis and 2 had typical inactive scars. Of the
      patients with active focus 3 had giant retinal tears, one had a posterior retinal
      tear and one had a retinal tear located at the edge of an atrophic scar. Of the
      patients with inactive lesions, one had tractional retinal detachment and the
      other presented with a complete retinal detachment, multiples tears and PVR. Five
      patients were treated by corticosteroid without antitoxoplasmic drug before they
      were referred. The seven patients underwent endo-ocular surgery with silicon oil
      or long actic gas tamponade. Three patients developed PVR and redetachment of the
      retina and two patients underwent further surgery. Good anatomical result was
      obtained in 6 patients. CONCLUSION: Retinal detachment associated with
      toxoplasmic retinochoroiditis is rare. However it represents a serious
      complication. Steroid administrated to salvage vision may then worsen the
      clinical course, these may be justified to reduce hypersensitivity to toxoplasma
      antigen, but they should be combined with an antimicrobial agent.

PMID- 9587589
TI  - [Ophthalmological manifestations of Von Recklinghausen disease].
AB  - PURPOSE: To evaluate the frequency of Von Recklinghausen neurofibromatosis type 1
      (NF1) ocular abnormalities. METHODS: A retrospective study was conducted in 11
      patients during two years. RESULTS: We found Lisch nodules in 4 cases associated
      to conjunctival lesion in one case and to retinal hamartoma in another case. In
      two cases, we found an eyelid neurofibroma. One patient had orbital fibrosis
      dysplasia. Ocular disease revealed the NF1 in 4 cases, the tumoral exophtalmia in
      two cases. CONCLUSION: The ocular manifestations of Von Recklinghausen disease
      are frequent and can reveal the disease. Ophthalmologic examination must always
      be performed if Von Recklinghausen is suspected.

PMID- 9587590
TI  - [Is there a role for Excimer laser in the treatment of keratoconus?].
AB  - PURPOSE: In advanced keratoconus, when contact lenses become intolerant or
      provide insufficient vision, the only current available treatment is penetrating
      keratoplasty. But getting a graft takes a long time; we evaluated the eventual
      role of Excimer laser in taking care of those patients. MATERIAL AND METHODS: We
      present a series of 8 advanced keratoconus, at that time, intolerant to contact
      lens because of a major ectasia and/or apical opacities. An excimer
      photoablation, using the therapeutic or rarely the refractive one, was performed
      in order to flatten or resurface the cornea, allowing a new contact lens fitting.
      RESULTS: We noted no complication, except a denser and longer postoperative haze.
      Thanks to a good compliance, 4 patients benefited from a new contact lens
      fitting, leading to an optimal visual recovery. On the other hand, in 3 cases, a
      corneal graft had to be performed, without any side effect. An anatomo-pathologic
      analysis was achieved on the 3 corneal caps, giving some precisions about
      tissular changes. CONCLUSION: Excimer laser, under its therapeutic approach,
      might be an efficient treatment for advanced keratoconus, in conditions of
      cautious indications selection and of an inevitable coupling to contactology.
      Then, this surgery could delay or even avoid penetrating keratoplasty.

PMID- 9587591
TI  - [Bilateral optic neuropathy disclosing primary Gougerot-Sjogren syndrome].
AB  - A case of optic neuropathy and central nervous system disease developed in
      association with primary Sjogren's syndrome is described. Initial visual loss was
      partially reversible with intra veinous steroid therapy but four months later she
      underwent a controlateral visual loss and showed for the first time clinical
      manifestation of sicca syndrome. Fluorescein angiography showed signs of ischemic
      choroidopathy. Laboratory studies and histological findings on minor salivary
      gland biopsy was suggestive of primary Sjogren's syndrome. Attempts to taper oral
      steroid therapy resulted in worsening neurological disease and immunosuppressive
      therapy by azathioprine was successfully added to her regimen. Because of
      therapeutics and prognosis consequences, primary Sjogren's syndrome should be
      considered in differential diagnosis of optic neuropathy.

PMID- 9587592
TI  - [Nevus of Ota associated with chronic glaucoma].
AB  - Oculodermal melanocytosis (nevus of Ota) is an abnormally large accumulation of
      pigment in ocular tissues as well as the skin in the distribution of the
      trigeminal nerve. Elevated intraocular pressure is a serious complication of this
      disease, as well as transformation to malignant melanoma. We report a case of
      nevus of Ota, documented clinically and histopathologically, associated with
      severe chronic glaucoma.

PMID- 9587593
TI  - [Differential diagnosis of conjunctival melanoma: exteriorized uveal melanoma].
AB  - Four years after unexplained left eye visual loss and 15 days after surgical
      procedure on the other eye, a 93-year-old female developed a pigmented left
      conjunctival lesion. Ultrasound examination demonstrated this lesion to be in
      fact an extraocular extension of uveal melanoma. The patient was treated by
      external radiotherapy after expanded enucleation.

PMID- 9587594
TI  - [Self-sealing sclerotomies in pars plana vitrectomy].
AB  - PURPOSE: To study a technique of self-sealing sclerotomies, recently described.
      METHODS: After conjunctival peritomy, a tunnel incision is performed with a
      crescent knife, 2 mm posterior to the intended site of entry. Then a 20G
      microvitreoretinal blade is used to enter the vitreous cavity. From November 1996
      to April 1997, 99 primary vitrectomies were prospectively studied. RESULTS: 292
      sclerotomies were performed with this technique. Self-sealing sclerotomies were
      observed in 270 cases (92.5%). In 22 cases, leakage of fluid required closure
      with 8-0 nylon sutures. Leakage was related to multiple instruments used through
      the sclerotomy, or more frequently to a thin scleral wall. In 1 case, transient
      hypotony was observed. Ocular pressure spontaneously returned to normal.
      CONCLUSIONS: Self-sealing sclerotomies are difficult to perform if the sclera is
      thin, and leakage can be observed if multiple instruments have to be used through
      the same sclerotomy. But this technique prevents vitreous and retinal herniation
      through the sclerotomy, and ocular hypotony. It also reduces the operative time,
      and prevents irritation related to nonabsorbable sutures.

PMID- 9587595
TI  - [Different types of Botulinum toxin and their comparison. Bioequivalence of
      toxins A and future therapeutic developments].

PMID- 9587597
TI  - [Radial keratotomy for myopia].

PMID- 9587596
TI  - [Retinal detachment].

PMID- 9587598
TI  - Eighty-year research of phlebotomine sandflies (Diptera: Psychodidae) in China
      (1915-1995). II. Phlebotomine vectors of leishmaniasis in China.
AB  - The human leishmaniasis vector--phlebotomine sandfly--was proven in China, i.e.
      P. alexandri, P. chinesis, P. longiductus, P. sichuanesis and P. smirnovi. The
      infectious rate, biology and distribution of these vectors are shown in this
      review. Two disputed questions about P. chinensis and P. sichuanesis, P. smirnovi
      and P. wui are discussed. At last, the vectors of animal leishmania are provided,
      i.e. the vectors of great gerbil leishmania: P. alexandri, P. andrejievi, P.
      caucasicus, P. mongolensis and P. smirnovi, and the vector of lizards leishmania:
      S. sinkiangensis.

PMID- 9587599
TI  - Chronobiology of Plasmodium chabaudi chabaudi: analysis of hourly recorded total
      and differential parasitaemia during a schizogonic cycle.
AB  - Detailed total and differential parasitaemia curves of asexual Plasmodium
      chabaudi chabaudi erythrocytic stages were recorded and analysed. Female, inbred,
      CBA/Ca mice were infected with the virulent IP-PC1 strain after in vitro
      synchronization of the parasites. Thin blood smears were made on an hourly basis,
      and the total and differential parasitaemia of ring forms, trophozoites and
      schizonts were counted after Giemsa staining. These curves reveal information
      that remains hidden when less detailed curves are examined: the duration and
      periodicity of the schizogonic cycle, the existence of a plateau, indications of
      a schizont withdrawal from the peripheral blood, the timing of the rise of the
      parasitaemia at each schizogony, and the invasion rate of the merozoites. In the
      perspective of developing a rational and efficient strategy for chronotherapy of
      malaria, such information should be taken into account.

PMID- 9587600
TI  - In utero transmission of Pneumocystis carinii sp. f. oryctolagi.
AB  - Although vertical transmission of Pneumocystis in human or animal hosts has often
      been suspected, no evidence demonstrating this infection route has been furnished
      until now. This widespread parasite is constantly found in the lungs of rabbits,
      which spontaneously develop a benign pneumocystosis at weaning. However, the
      infection source, the method of entry of Pneumocystis organisms into the rabbit
      and when this mammal is infected, remain to be known. As a few parasites have
      been microscopically observed and detected by PCR in the lungs of rabbits at
      birth, in utero Pneumocystis infection has been hypothesized. The presence of
      Pneumocystis was therefore carefully assessed in 16 pregnant does, their embryos
      and fetuses by using several detection methods. Pneumocystis was detected by PCR
      in maternal blood, embryos, amniotic fluid and fetuses. The parasite was also
      revealed histologically and by immunofluorescence in fetal and maternal lungs and
      in placentas. The results suggest that vertical transmission of P. carinii sp. f.
      oryctolagi occurs as early as at the 10th day of pregnancy.

PMID- 9587602
TI  - Some quantitative aspects of natural babesial infection in the haemolymph of
      Boophilus microplus engorged female ticks.
AB  - Quantitative aspects of the natural babesial (Babesia bovis and Babesia bigemina)
      infection in Boophilus microplus engorged female ticks obtained from two herds of
      Holstein heifers positive by the immunofluorescent antibody test to both
      protozoan were evaluated. The number of kinetes/microscope field of haemolymph
      was determined for each tick from day 5 to 10 post-collection. A close
      relationship between daily and cumulative babesial infection was detected.
      Correlation and determination coefficients between days post-collection and the
      daily and cumulative infection rates, including heavily infected ticks (those
      ticks carrying at least 3.0 kinetes/microscope field of haemolymph), were always
      higher than 0.9 (P < 0.01) in ticks of both herds. The median was found to be a
      more representative measure than the mean to define the distribution of kinetes
      number amongst infected ticks since this is a negative binomial distribution. The
      analysis of the sequential order of days of infection more accurately showed the
      amplification of the babesial infection in the tick haemolymph than the evolution
      of kinetes number in relation to days post-collection. Sampling ticks on days 8,
      9 and 10 post-collection would have detected all ticks infected with Babesia spp.
      from both herds. A categorization of infected or non infected ticks would be of
      greater epidemiological importance than the haemolymph infection level, based
      upon previous laboratory studies that showed a poor relationship between
      haemolymph infection in the female ticks and the infection rate in their eggs.
      However, further studies in natural infected ticks and better techniques to
      differentiate B. bovis and B. bigemina kinetes are needed before these laboratory
      results can be applied to field conditions.

PMID- 9587601
TI  - Activity of pentamidine-loaded poly (D,L-lactide) nanoparticles against
      Leishmania infantum in a murine model.
AB  - The activity of pentamidine-loaded poly(D,L-lactide) nanoparticles was compared,
      by determination of median effective doses (ED50), to that of free pentamidine in
      a murine model of visceral leishmaniasis induced by Leishmania infantum. BALB/c
      mice were infected intravenously on day O with promastigotes and then treated on
      days 14, 16, and 18. Groups of 5 mice received either 0.57, 1.14 and 2.28 mg/kg
      of free pentamidine (expressed in pentamidine base) or 0.055, 0.11, 0.22 and 0.44
      mg/kg of pentamidine-loaded nanoparticles. In the control group, 12 mice received
      normal saline. The liver parasite burden was evaluated using the Stauber method
      72 h after the last injection and drug levels in livers and spleens were
      determined. Bound pentamidine was 3.3 times more active than free drug (ED50
      value = 0.32 mg/kg versus 1.05 mg/kg for free drug). Drug levels showed a weak
      accumulation in hepatic and splenic tissues following bound pentamidine
      administration. A lack of acute toxicity was noted in all groups treated by bound
      pentamidine. Results obtained with this biodegradable carrier may be of
      particular interest as no new major antileishmanial compound is today available.

PMID- 9587603
TI  - In vitro production and characterization of excretory/secretory products of
      Onchocerca volvulus.
AB  - Onchocerca volvulus excretory/secretory products [ESP] free of host contaminants
      are often needed for immunologic and biochemical studies. Since prolonged in
      vitro survival of O. volvulus in culture requires the presence of human serum, as
      a supplement, it was necessary to investigate other culture medium supplements in
      which pure ESP could be generated. Thus heat-inactivated normal rabbit serum,
      fetal calf serum and the synthetic serum substitute Ultroser-G were tested for
      their abilities to sustain O. volvulus adult females and nodular microfilariae in
      vitro and their abilities to promote the synthesis and release of ESP. Using
      [35S]-methionine as the radioactive precursor, O. volvulus nodular microfilariae
      and adult females were shown to actively synthesize and release
      excretory/secretory proteins with increasing efficiency in human serum, rabbit
      serum, Ultroser-G and fetal calf serum. Analysis of the ESP by SDS-PAGE revealed
      that at least 30 polypeptides in the 7-174 kDa range were continuously released.
      About 14 of these components were immunogenic to the human host as shown by
      immunoprecipitation. Prominent antigenic polypeptides were those with relative
      molecular weights of 13, 16, 33, 68 and 170. Rabbit serum, fetal calf serum and
      Ultroser-G could therefore, conveniently replace human serum in cultures of O.
      volvulus nodular microfilariae and adult females.

PMID- 9587604
TI  - [Intestinal microsporida infections in children with primary immunologic
      deficiencies].

PMID- 9587605
TI  - Lectins (hemagglutinins) in the gut of the important disease vectors.
AB  - The review is devoted to the gut lectins/hemagglutinins of the following
      representatives of important disease vectors: ticks, kissing-bugs, mosquitoes,
      sandflies and tsetse flies. The paper surveys the recent knowledge on these
      carbohydrate binding factors with respect to their structural and functional
      properties, and their significance for pathogen/parasite transmission by the
      blood-sucking arthropods. Recent results suggest that in most vectors the gut
      lectin activities are blood-meal enhanced, might participate in blood-meal
      processing and digestion and could serve as antibacterial and antiparasitic
      agents.

PMID- 9587606
TI  - [Control of intestinal schistosomiasis in Martinique island].
AB  - The presence of schistosomiasis mansoni is known in Martinique since the
      beginning of the XXth century. A general survey of the distribution of the
      disease was carried out in 1977 and showed a mean prevalence of 12% (coprology
      and serology taken together) in the whole of the island. Following this survey,
      an integrated control programme associating sanitary education, detection and
      treatment of patients and improved sanitation, was developed. In addition, a
      biological control programme against the intermediate snail host, Biomphalaria
      glabrata using the competitor snail, Melanoides tuberculata, was developed in the
      transmission sites. The decline of snail populations and of its parasite, as well
      as a strong reduction of the prevalence in humans were recorded between 1977 and
      1996. At the present time, only few cases corresponding to older infections are
      detected. This epidemiological situation is quite different from that in
      Guadeloupe island where, in spite of an excellent control programme which was
      achieved on the Basse-Terre district, an important focus is still functioning on
      Grande-Terre district with the black rat as host reservoir. Such foci do not
      exist on Martinique island.

PMID- 9587607
TI  - Tapironema coronatum n. gen., n. sp. (Trichostrongyloidea-Cooperiidae
      Obeliscoidinae), a parasite of Holochilus brasiliensis and Tapirus terrestris.
AB  - In this paper we provide a description of Tapironema coronatum n. gen. n. sp.
      (Trichostrongyloidea, Obeliscoidinae) from the cricetid Holochilus brasiliensis
      or "water rat" in Argentina (Type material) and from Tapirus terrestris in French
      Guyana (voucher material in poor condition). The new genus is characterized by a
      corona radiata, an oesophageal tooth, a bilaterally synlophe with about 73
      (male), 122 (female) cuticular ridges, a caudal bursa pattern 2-1-2 with rays 5
      and 6 parallel and close together and rays 5 longer than rays 3. The most closely
      related genus is the monospecific Teporingonema Harris, 1985, from a Mexican
      lagomorph, Romerolagus. The cephalic extremity of this parasite is redescribed
      after the type-material. The systematic position of Teporingonema amongst the
      Obeliscoidinae is defined and the hypotheses concerning the origin of this sub
      family are provided.

PMID- 9587608
TI  - A biological role for haemagglutination activity of Leishmania promastigotes and
      amastigotes.
AB  - Leishmania promastigotes and axenic amastigotes possess a haemagglutination
      activity (HA). Leishmania attachment to human macrophages was studied after a 30
      min incubation in the presence of 10 mM carbohydrates at 37 degrees C.
      Galactosamine, sialic acid, heparin, mannose, and NAc-mannosamine impaired the
      attachment of promastigotes and amastigotes to monocyte-derived macrophages and
      the myelomonocytic cell line THP 1 whereas other carbohydrates had no effect.
      Preincubation experiments showed that mannose inhibits the macrophage receptor,
      whereas galactosamine acts on promastigotes. Moreover, the HA is considerably
      decreased after incubation with macrophages. Our results suggest that
      promastigotes of different Leishmania species and axenic amastigotes possess a
      lectin-like receptor with similar specificity, which is in some way involved in
      the attachment to vertebrate host cells.

PMID- 9587609
TI  - A universally applicable internal standard for PCR detection of Wuchereria
      bancrofti in biological samples.
AB  - A PCR-based assay have been previously described to detect Wuchereria bancrofti
      in mosquitoes and in human blood samples. However, the efficiency of PCR
      amplification may vary between samples depending on the presence of PCR
      inhibitors, leading sometimes to false negative results. To overcome this
      drawback, an internal standard plasmid (pWB11) was constructed. It can be added
      to each PCR reaction for coamplification along with the target W. bancrofti DNA
      (Sspl DNA repeat) using the same pair of primers. PCR products from W. bancrofti
      DNA or from pWB11 are 34 bp different in size and can be visualized either on
      agarose gel or by DNA ELISA using two different oligonucleotides probes.

PMID- 9587610
TI  - Effect of itraconazole on lytic antibodies levels in chronic Chagas disease.
AB  - We report the chemotherapeutic effect of itraconazole in chronic chagasic
      patients. The efficacy of treatment was analyzed by xenodiagnosis (XD),
      conventional serology (CS) and antibody dependent-complement mediated lysis test
      (CoML). Twenty chronic chagasic persons from endemic areas of Chile were grouped
      according to the results of xenodiagnosis (XD) performed before therapy. The
      follow-up of patients was performed at an average time of 42 months after
      treatment. No significative statistical differences were observed in the result
      of ELISA and Indirect Immunofluorescence test performed on serq before and after
      therapy with itraconazole. In the group of patients with positive XD before
      therapy, sera from six of them displayed lytic activity against Trypanosoma
      cruzi. The lytic activity of only one of these sera became negative after
      therapy. In relation to XD, five of those patients showed a positive tests at
      least once during the follow-up period. In the group of ten patients with
      negative XD before therapy, sera from eight of them displayed lytic activity. At
      the end of the follow-up period seven of them became negative. Nine of the ten
      patients maintained their original condition with respect to XD. These results
      suggests that parasitaemia level before therapy condition could be an important
      parameter to consider in the chemotherapy of chronic Chagas disease.

PMID- 9587611
TI  - Relapsing Plasmodium vivax malaria with atypical parasite forms and phagocytosis
      by peripheral neutrophils.
AB  - A case of atypical Plasmodium vivax malaria is presented. The clinical follow-up
      has allowed to characterize three consecutive malaria clinical episodes within
      one year. At the first attack, 39% of the infected red blood cells were
      parasitized by gametocytes. Furthermore, rare crisis forms, exceptional
      "pseudoparthenogenesis" forms, a few equatorial trophozoites, malaria pigment
      containing leucocytes and phagocytized parasites were also found in the thin
      blood smears. At the second malaria episode, morphological aspects were quite
      similar, but the gametocyte percentage decreased and that of the equatorial
      trophozoite forms increased. Only at the third attack, was the morphology typical
      of P. vivax. The Plasmodium species and the absence of mixed infection were
      unequivocally confirmed using polymerase chain reaction. Atypical strains of P.
      vivax are relatively frequent. Nevertheless, to our knowledge, neither so high a
      gametocyte percentage, nor extensive P. vivax peripheral phagocytosis were
      previously reported.

PMID- 9587612
TI  - A comparison of two antigen-detection ELISA for detecting infection of
      Dirofilaria immitis in dogs.
AB  - A survey on 87 dogs necropsied in the Townsville region revealed 34 (39%) were
      infected with Dirofilaria immitis. Infected dogs had an average of 6.1 adult
      worms in the heart and associated blood vessels. The VetRED assay detected 23 of
      the 34 infected dogs (sensitivity 65%) and the Og4C3 ELISA detected 27
      (sensitivity 80%). Sensitivity of the VetRED and Og4C3 ELISA increased to 88 and
      94% respectively in dogs with three or more worms. Both tests detected correctly
      all uninfected dogs. Despite the higher accuracy of the Og4C3 ELISA, compared to
      the VetRED assay, it is unlikely to be used widely as a field test for heartworm
      unless it can be modified from its present plate ELISA format which takes 4
      hours, into one which is more rapid and convenient. However, as a reference
      ELISA, it may well be worthwhile in situations which require considerable
      accuracy for detecting D. immitis infection.

PMID- 9587613
TI  - [Diagnostic value of the demonstration of specific antigens of Fasciola hepatica
      by western blot technique].
AB  - A western blot assay was performed for the detection of Fasciola hepatica
      specific antigens for the diagnostic of fasciolasis; 72 sera were tested, 28
      coming from patients with the parasitic disease and 44 from persons either
      healthy or presenting other diseases; 11 different antigenic bands were detected
      using sera from patients with fasciolasis. The 57 and 29 kDa specific antigens
      are considered like major, their specificity is about 100% and their respective
      sensibility, 79 and 93%. Band of 9-12 kDa is also appeared specific but is
      revealed only in 47% of the cases; 27 out of the 28 sera from patients with
      fasciolasis were able to recognize at least one of the 57, 29 or 9-12 kDa
      specific antigens. The present results suggest that western blot could be useful
      for the diagnosis of this parasitic disease as far as the criteria of positivity
      is based on the recognition of at least one of the major specific antigens.

PMID- 9587614
TI  - [Pseudarthrosis treated by percutaneous autologous bone marrow graft].
AB  - PURPOSE: This study characterizes the bone marrow from 35 non union sites, not
      only with respect to the medullary stroma but also the hematopoietic compartment.
      In this study, we looked for systemic anomalies which could explain
      susceptibility to non union. We also compare the in vitro activity of bone marrow
      taken from non union sites with that of samples taken from the iliac crest, of
      the same patient. MATERIAL AND METHODS: We included 6 groups: 26 cases of post
      traumatic non union. 2 cases of non union following arthrodesis of the knee for
      infected prosthesis, 1 case of a non union of a tibiotarsal arthrodesis. 4 cases
      of regenerated illizarov extensions, which showed no evidence of ossification
      three months after operation, 2 cases of patients suffering from congenital
      abnormalities. Samples were taken from a population of 30 "bone marrow donors",
      to act as controls for the iliac crest samples. RESULTS: Cell density in the
      iliac crest bone marrow of non union patients is significantly lower than that of
      controls (p < 0.01). In the hematopoietic compartment of the bone marrow, the
      number of progenitors (GM-CFU) obtained after culture of iliac crest bone marrow
      is consistently lower for patients presenting a non union than for controls (p <
      0.01). Only infection of non union site (4 cases) seems to be associated with an
      increase in GM-CFU in the iliac crest. The difference in the average number of F
      CFU obtained after culture of bone marrow from non union patients and from
      controls is lower but is nevertheless significant. 14 of the non union patients
      have less than half the F-CFU observed as normal in controls and 10 of them
      yielded less than one quarter. Out of these ten patients, in whom non union was
      associated with a marked abnormality in the number of F-CFU in the iliac crest
      (less than one quarter of the total obtained from controls), in 8 cases were
      other factor or disease which could account for the abnormality such as age (2
      cases), clear alcoholic intoxication (1 case), heavy smoking (2 cases), history
      of chemotherapy (2 cases), and Lobstein's disease (1 case). The values found in
      non union sites and extension regenerated fibrous tissue suggest that there are
      relatively few F-CFU to differentiate into fibroblasts. In 12 out of 35 patients
      studied, the bone marrow generated no F-CFU. Same patients have abnormal low
      levels of F-CFU obtainable from their iliac crest bone marrow. The number of GM
      CFU in fracture site is also extremely low. No local increases in GM-CFU levels
      are seen in septic focuses. The population of F-CFU and GM-CFU vary with time, in
      the same patient, at the same site of aspiration. Higher levels of osteogenic
      activity are seen at the beginning of extension. CONCLUSION: This study suggests
      that problems related to consolidation may be linked with an overall reduction of
      bone marrow progenitor cells, as a result of some general physiological problem
      (chemotherapy, smoking, alcoholic poisoning).

PMID- 9587615
TI  - [Reconstruction of the anterior cruciate ligament by bone-patellar tendon
      transplant. Evaluation of 79 cases. Prognostic factors].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to evaluate the results of
      the anterior cruciate ligament (A.C.L.) reconstruction according to two scoring
      systems (Arpege and IKDC), to analyse the influence of different factors on the
      results, to study the effect of a lateral extra-articular tenodesis, the
      morbidity of patellar tendon graft harvesting, and the advantage of
      arthroscopically assisted reconstruction. MATERIAL: Seventy nine patients, 17 to
      39 years old (average 27 years), underwent an anterior cruciate ligament
      reconstruction for chronic instability, using a free bone-patellar tendon-bone
      graft. In 43 cases, a lateral extra-articular plasty was added (Lemaire's
      procedure). The reconstruction was arthroscopically assisted in 17 cases.
      Interval between initial injury and surgery was 24 months (2 months to 9 years
      and 7 months). The average follow-up was 2.5 years (range 1 to 18). METHOD: All
      patients were reviewed for evaluation with two scoring systems (Arpege and IKDC).
      Roentgenograms of both knees, including antero-posterior weight-bearing and
      lateral view, patellar view, dynamic radiographs, allowed evaluation of post
      operative arthrosis and residual anterior laxity in extension. Fischer's test and
      chi square test were used for statistical evaluation. RESULTS: Using the Arpege
      CLAS system, functional results were excellent or good in 75.9 per cent of cases
      (excellent in 44.3 per cent, good in 31.6 per cent), fair in 15.2 per cent, poor
      in 8.9 per cent; according to the IKDC system, 65.8 per cent were excellent or
      good. 84.8 per cent of the patients were satisfied in Arpege system and 91.2 per
      cent in IKDC system. The pivot-shift test was negative in 86 per cent, equivocal
      in 7.6 per cent and positive in 6.4 per cent. The radiological Lachman's test
      (difference between control and affected knee) was 0-2 mm in 53.2 per cent, 3-5
      mm in 39.2 per cent, 6-10 mm in 7.6 per cent, never greater than 10 mm. Antero
      posterior weight-bearing radiographs were normal in 83.5 per cent, showed joint
      remodeling in 10.1 per cent pre-arthrosis in 6.3 per cent but no arthrosis.
      Functional results were not correlated with age at time of surgery, interval
      between initial injury and surgery, nor clinical Lachman's test. Competitive
      sportsmen had a better result (p = 0.001). Residual laxity in extension was
      correlated with lesions of medial meniscus (p = 0.035). Degenerative changes in
      femoro-tibial joint were correlated with residual laxity in extension (p =
      0.019). There was no significative difference between A.C.L. reconstruction
      isolated or associated with lateral extra-articular tenodesis. Time to return to
      work was shorter for patients with arthroscopically assisted procedure (p =
      0.067). DISCUSSION AND CONCLUSION: Functional results after A.C.L. reconstruction
      using a free bone-patellar tendon-bone graft are satisfactory and confirm the
      reliability of this procedure. Arpege CLAS and IKDC systems give comparable
      functional results, but IKDC evaluate anatomical results, residual laxity and
      degenerative changes of the joint, that constitute essential long-term pronostic
      factors. Morbidity of patellar tendon harvesting appears to be of short duration
      and largely reversible. Added lateral extra-articular tenodesis doesn't improve
      the results. Arthroscopically assisted procedure seems to allow a faster
      rehabilitation.

PMID- 9587616
TI  - [Common fibular nerve lesions. Etiology and treatment. Apropos of 146 cases with
      surgical treatment].
AB  - PURPOSE OF THE STUDY: Common peroneal nerve lesion on the lateral aspect of the
      knee is one of the most frequent neurologic injury of the lower limb. We reported
      the results of surgical procedure for each etiological group. MATERIAL AND
      METHODS: In the peroneal nerve entrapment group, we individualised 62 fibular
      tunnel syndroms (55 idiopathic, 4 postural, 3 dynamic), and 16 external
      compression. Traumatic causes were represented by 22 varus injuries of the knee
      and by 11 fractures, 16 iatrogenic lesions, 2 wounds, 5 wound sequelae, 2
      contusions and 1 burn. Tumoral group was represented by 7 intraneural ganglionic
      cyst and 2 extraneural tumour (1 exostosis and 1 chondromatosis of the proximal
      tibio fibular joint). All patients underwent surgical procedure. Neurolysis was
      performed when the nerve was in continuity. Suture or nerve grafting was
      performed in the other cases. In the case of intraneural ganglionic cyst, a
      complete tumoral excision was realised. RESULTS: Eighty-three per cent of
      excellent and good results were obtained for the fibular tunnel syndrom, 62.5 per
      cent for external compression, 36 per cent for varus injury of the knee, 78 per
      cent for the other traumatic causes and 89 per cent for tumoral lesions.
      DISCUSSION: This report confirms that the result depends on the etiology of the
      common peroneal nerve lesion. We propose surgical treatment within 2 to 4 months
      for the patients without clinical and electrophysiological improvement. If there
      is doubt on the continuity of the nerve, we propose an earlier surgical
      treatment. Our results were in general satisfactory except when a nerve graft was
      necessary furthermore if it was a traction injury and if the length of the graft
      was longer than 6 centimeters.

PMID- 9587617
TI  - [Effect of the rotator cuff condition on the results of shoulder arthroplasty].
AB  - PURPOSE OF THE STUDY: The purpose of this report was to study the repercussions
      of rotator cuff condition on unconstrained shoulder arthroplasty results.
      METHODS: Between 1986 and 1993, 40 unconstrained shoulder prostheses were
      performed (24 total and 16 hemiarthroplasties). At the time of the operation,
      rotator cuff condition was reported to be normal in 15 shoulders, atrophic in 10,
      scarred in 3, torn in 12. Clinical and radiographical results were analyzed and
      supplemented with a rotator cuff echography. Postoperative follow-up averaged
      42.25 months (12 to 97 months). RESULTS: When the rotator cuff was intact at the
      time of operation, clinical results were the best at the time of review. Constant
      score, overall mobility, forward elevation, external rotation with the elbow
      along the side were better for intact than for atrophic, scarred or torn rotator
      cuffs (p < 0.01). Ruptures repaired by local tissue transfer or trapezo deltoidal
      flap substitution (3 cases) gave satisfactory results, whereas two dacron cuff
      prostheses failed. In the non repaired ruptures (7 cases), arthroplasty resulted
      in 3/4 fair or poor results. At the time of review, the total incidence of
      postoperative rotator cuff tears was high (12 cases), functional repercussions
      were variable. Among the 15 rotator cuff tears observed at the time of the
      review, the long head of the biceps was present and in place in 9 cases and
      ruptured in 6 cases. In these latter cases, Constant score (p < 0.01), the
      forward elevation (p < 0.01), external rotation with elbow along side (p < 0.05)
      and overall mobility (p < 0.05) were worse; moreover, humeral head superior
      migration was greater (p < 0.01). DISCUSSION: Our study confirms the superiority
      of clinical results when the cuff was intact at the time of the operation. The
      repair of rotator cuff tears seems to be justified. When the rupture has not been
      repaired, clinical results were fair or poor in 5 cases out of 7, the initial
      rupture spread to the other tendons in 3 cases out of 7. Secondary ruptures were
      frequent (12 cases). No predictive factor was identified, but an overlapping of
      the greater tuberosity appears to be detrimental. Among rotator cuff tears
      present at the time of review, long head of the biceps rupture jeopardized
      clinical results and was associated with a proximal migration of the humeral head
      which was significantly more severe than with an intact non displaced long head
      of the biceps. CONCLUSION: During unconstrained shoulder prosthesis implantation,
      it is therefore recommend to systematically repair any associated rotator cuff
      rupture, in order to avoid any greater tuberosity overlap relative to the
      prosthetic head and to preserve the long head of the biceps tendon which limits
      upward migration of the humeral head and improves prosthetic kinetics.

PMID- 9587618
TI  - [Lower limb morphotypes. A clinical study in 1401 children].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to analyse the repartition
      between femoral anteversion and tibial torsion from birth to ten years of age in
      children. MATERIAL: One thousand four hundred and one children ranging from 2 to
      13 years age were examined in public schools by the same clinician. METHODS:
      Qualitative data (foot progression angle, hindfoot aspect, knee position during
      gait) and quantitative data (femoral anteversion, tibial torsion) were clinically
      quantified. RESULTS: Repartition of femoral and tibial torsion showed four lower
      limb morphotypes in normal children. CONCLUSION: Four femoral anteversion and
      tibial torsion associations are encountered in normal children. Age variation of
      the lower limb orientation leed to have repetitive examinations in children with
      in or out-toeing gait in order to make distinction between normal and pathologic
      gait pattern.

PMID- 9587619
TI  - [Osteochondral fractures of the external femoral condyle after traumatic patellar
      dislocation during physical exercise in children].
AB  - PURPOSE OF THE STUDY: Nineteen osteochondral fractures of the lateral femoral
      condyle associated with acute traumatic patellar dislocation resulting from sport
      injury in children were studied. The purpose of this study was to specify
      clinical and radiological features. MATERIAL AND METHOD: This study was led with
      special care to injury circumstances, fracture visibility on X-rays, size and
      location of the fracture, treatment delay, presence of femoro-patellar dysplasia
      signs. Treatment results were evaluated on knee pain, bone consolidation and
      recurrent dislocation. RESULT: Thirteen boys and six girls aged 8 to 16 years
      (average 14 years) were included. The injury resulted from a rotatory-compression
      stress in 75 per cent cases. The patella was always in place at the time of
      examination. Thirteen fractures were diagnosed within 24 hours and 5 fractures
      were diagnosed within 1 week after injury. One fracture was not visible on X-rays
      and was diagnosed 6 weeks after injury. Only the lateral view showed the fracture
      in more than one case out of two. Seven patients whose fracture was less than 5
      mm, or involving a non-weight-bearing portion, or diagnosed within more than ten
      days after injury, were treated by knee arthroscopy and removal of the
      osteochondral fragment. Twelve patients were treated by arthrotomy and excision
      (one case) or replacement of the osteochondral fragment (11 cases). The replaced
      fracture was fixed with biological glue ten times, and screwed once. The knee was
      immobilised in a cylinder cast and weight-bearing prohibited for six weeks. Bone
      consolidation was obtained in 9 cases out of 11, in an average of 8 weeks. Knee
      pain occurred 5 times. Recurrence of the dislocation occurred 3 times within 6
      months. Eighty per cent of these children showed patello-femoral dysplasia.
      DISCUSSION: This fracture complicated 31.6 per cent of traumatic patellar
      dislocation resulting from sport injury in children which we observed during the
      last ten years. It may be overlooked if it is suspected and carefully looked for
      by radiographic examination including antero-posterior, lateral, oblique and true
      skyline views of the patella. The presence of fat in the hemarthrosis may help.
      Early surgery is recommended. Arthroscopy may be performed to evaluate fracture
      location and size. After ten days, host area begins to fill in and free fragment
      will not fit back well. Fragments less than 5 mm, or involving a non-weight
      bearing portion, or diagnosed within more than ten days after injury, may be
      removed. CONCLUSION: Lateral femoral condyle osteochondral fractures are
      associated with nearly one third of traumatic patellar dislocation resulting from
      sport injury in children. A detailed radiographic examination can help diagnosis.
      Treatment depends on the delay after injury, the size and location of the
      fracture.

PMID- 9587620
TI  - [Distal humeral fracture in adults: functional evaluation and measurement of
      isometric strength].
AB  - PURPOSE: The purpose of the study was to determine prognostic parameters in adult
      distal humeral fracture. MATERIAL: Thirty patients were reviewed retrospectively
      at a mean follow-up of 5 years. According to the AO classification there were 5
      type A, 5 type B and 20 type C fractures, of which 7 were open. An internal
      fixation was performed in 27 patients while 3 cases were treated conservatively.
      An olecranon osteotomy was performed in 8 patients. A bilaterotricipital approach
      according to Alonso-Llames was performed in 8 cases while 6 times a V-shaped
      section of the triceps and 3 times a transtricipital approach were performed. A
      lateral approach and a combined medial and lateral approach were performed one
      time each. Active-assisted motion begun in 19 patients before the fifth post-op
      day. Three secondary displacements required reoperation. METHOD: The assessment
      included a questionnaire, a physical as well as radiological examination and
      measurements of isometric flexion and extension strength of both elbows.
      Statistical correlations were performed using non parametric tests at a P < 0.05
      level. RESULTS: Average flexion was 127 degrees, while there was an average lack
      of extension of 29 degrees. Pronation and supination were respectively 68 degrees
      and 85 degrees. Twenty-two patients were subjectively satisfied with their elbow.
      The measurements of isometric strength of the fractured elbow showed that the
      right side which was dominant in the whole population was statistically weaker at
      follow-up than the left side. This difference was significant for flexion
      strength (Wilcoxon test P = 0.028) and highly significant for extension strength
      (Wilcoxon test P = 0.0002). The surgical approaches also influenced strengths.
      The Alonso-Llames approach was thought to give a better result than the other
      approaches. Patients mobilized before the fifth post-op day showed a
      statistically better flexion than patients mobilized later on (exact Fisher test
      P = 0.013). The difference was not statistically significant for the extension.
      DISCUSSION AND CONCLUSION: The distal humeral fracture produces a decrease of the
      elbow strength which is more severe for the dominant side. The reason is unknown.
      The Alonso-Llames approach seems to be the most favorable approach while the V
      shaped section of the triceps shows a deleterious effect on strength. Early post
      op exercises seem to have a positive effect on the long term ROM. Neither the
      fracture type (classification) nor the ROM, nor the strength are correlated with
      the subjective feeling of the patient. On the other hand statistical correlations
      show that unsatisfied patients are heavy workers (exact Fisher test P = 0.033)
      and patients younger than 60 years old (exact Fisher test P = 0.029).

PMID- 9587621
TI  - [Bad clinical results of cemented caps with metal-backed acetabular components.
      124 cases with 21 months follow-up].
AB  - PURPOSE OF THE STUDY: The authors reviewed with short term follow-up 124 total
      hip arthroplasties using a cemented metal-backed acetabular component. The
      purpose of the study was to evaluate clinical and radiological results because of
      early periacetabular radiolucent lines reported by Ritter. MATERIAL AND METHODS:
      Surgical procedures were performed in 1988 and 1989 with Saint-Antoine prosthesis
      (PSA) including cemented titanium metal-backed socket. Functional results were
      appreciated with Postel-Merle d'Aubigne's score. Radiological results were
      appreciated using De Lee and Charnley's criterias for radiolucent lines and
      Yoder's criterias for socket's migrations. We studied correlation between
      radiolucent line and age, weight, hip disease, associated bone graft, socket size
      and technical errors. RESULTS: With short term follow-up (21 months), we found
      60.4 per cent hips with a maximal PMA score (18) with an average score of 17.5
      per cent. We observed 26.4 per cent of complete periacetabular radiolucent lines
      with 3 sockets loosening with migration. No significant correlation were found
      between radiolucent lines and age, weight, hip disease, associated bone graft,
      socket size, and technical errors. DISCUSSION: This periacetabular radiolucent
      line rate was comparable to the results of the series using such a cemented metal
      backed socket. This rate was clearly higher than the results of others series
      using cemented polyethylene sockets. These bad results were not correlated to
      those of finite elements analysis. We think that this is due to metal-backed
      socket excessive rigidity. CONCLUSION: Because of this high periacetabular
      radiolucent line rate, despite of finite elements analysis results, we no more
      use cemented metal-backed acetabular socket since 1991.

PMID- 9587622
TI  - [Haglund disease treated by simple resection of calcaneus tuberosity. An angular
      and therapeutic study. Apropos of 74 cases with 2 years follow-up].
AB  - PURPOSE OF THE STUDY: The authors report the treatment of Haglund's disease,
      using a simple os calcis tuberosity resection. They reviewed long term results
      and the value of radiological criteria for pre-operative evaluation. MATERIAL:
      The series included 54 patients (74 feet) mostly female and young. The simple
      resection of os calcis tuberosity was performed without further operation or post
      operative splint. METHODS: Post-operative results were appreciated according to 3
      criteria: pain, functional activity and shoe wearing. Radiological criteria used
      Fowler and Philip angle, angle of calcaneal inclinaison, total angle, CL angle,
      Denis and Huber-Levernieux test and Heneghan and Pavlov parallel lines.
      Correlation tests with simple regression were used for statistical analysis.
      RESULTS: Results were graded as excellent and good in 73 per cent fair in 16.2
      per cent and poor in 10.8 per cent cases. DISCUSSION: Results were compared to
      other series. Neither radiological criteria, angular or not, can rule out simple
      tuberosity resection, because results showed no relation between test and angle
      measurements. There is no correlation between post-operative radiographs and
      final result. The only efficient criteria of resection is the difference between
      Fowler and Philip, and CL angles. This technique may be recommended after few
      months of medical treatment, without using calcaneal osteotomies of Zadek type.
      CONCLUSION: The simple resection of os calcis tuberosity showed good results in
      73 per cent cases at an average follow up of 6 years 9 months.

PMID- 9587623
TI  - [A rare diaphyseal bone tumor: degenerative mucoid cyst].
AB  - The purpose of the study was to clarify the clinico pathological features of
      periosteal ganglion. The authors present a case of an unusual diaphyseal bony
      tumor in a 27 years old man. The diagnosis of diaphyseal periosteal ganglion cyst
      was made on roentgenographic appearance, presence of mucoid material and
      histologic evidence of a synovial type cellular lining. The patient was
      successfully treated with excision. The follow-up examination showed no
      recurrence one year after surgery. The radiological differential diagnosis were
      considered and possible pathogenes for a periosteal ganglion was discussed.
      Periosteal ganglia must be considered as a cause of cortical erosions. This
      lesion may radiologically mimic other periosteal lesions. Treatment with excision
      is successful in most cases.

PMID- 9587624
TI  - Long term effects of spinal cord transection in zebrafish: swimming performances,
      and metabolic properties of the neuromuscular system.
AB  - This study concerns functional recovery of zebrafish following spinal cord
      transection. Spinal cords were transected at the level of the 14th vertebra, just
      rostral to the dorsal fin. Recovery was tested at one month after transection
      when descending fibers start to regrow across the transection site and at three
      months after transection when fish perform kick and glide swimming. To estimate
      the rate of regrowth across the lesion site we analysed the tyrosine hydroxylase
      (TH) and dorsal 5-hydroxytryptamine (5-HT) systems in distal parts of lesioned
      cords. Both systems have cell bodies in the brainstem and in control fish TH- and
      dorsal 5-HT-containing fibers descend to all spinal segments. Swimming
      performance was studied by subjecting lesioned fish to endurance tests in a
      swimming tunnel with water flowing at a constant rate of 2 or 4.5 body lengths
      per second (BL/s). At 2 BL/s slow myotomal muscles are active whereas at 4.5 BL/s
      fast myotomal muscles are recruited. Control fish endured sustained swimming at
      both speeds for at least 3 hours. As a measure for the condition of the
      neuromuscular system in trunk and tail, we analysed aerobic metabolic capacities,
      assessed by NADH-tetrazolium reductase (NADH-TR) histochemistry of myotomal
      muscle fibers and spinal lateral neuropil. We found that TH- and dorsal 5-HT
      immunoreactive fibers were absent in the entire distal part of lesioned cords at
      one month but at two months after transection they were present at approximately
      6000 microns caudally to the site of the lesion. Thus the rate of outgrowth of
      these fibers is at least 200 microns per day. Sustained swimming at the slow
      speed (2 BL/s) could be endured for about 14.4 min at one month and for 23.5 min
      at two months after transection; there was no further improvement in the period
      that followed. In contrast, in the 10 weeks following transection, fast swimming
      (4.5 BL/s) could be endured for about 5 to 6 minutes. A significant improvement
      was gained in the period of 10 to 12 weeks after transection when fish could
      endure the high speed for almost 15 min. The aerobic capacity of muscle fibers in
      distal parts of the body was not strongly affected by the lesion. The only
      important change in aerobic capacity was observed in the neuropil of distal parts
      of the cords where, at three months after transection, NADH-TR activity was
      increased to approximately 150% of control values. On the basis of our findings,
      we assume that it is not the condition of the neuromuscular system, but rather a
      deficient co-ordination between proximal and distal body parts of lesioned fish
      that accounts for the relatively poor performances in endurance tests.
      Furthermore, differences in timing of improvements in swimming at 2 and 4.5 BL/s
      indicate that the spinal circuitries serving the slow parts of the neuromuscular
      system recover at an earlier stage than those serving the fast parts.

PMID- 9587626
TI  - Galanin-like immunoreactive nerve fibres in the anterior pituitary of the normal
      and adrenalectomized rat.
AB  - Our previous studies have shown the presence of substantial amounts of substance
      P and calcitonin gene-related peptide-like immunoreactive nerve fibres in the
      anterior pituitary of the monkey, dog and rat. Furthermore, synaptic
      relationships have been demonstrated between these nerve fibres and the gland
      cells in the dog and rat. The substance P and calcitonin gene-related nerve
      fibres increase in number following adrenalectomy and ovariectomy, respectively.
      The present study was aimed to investigate the galanin-containing nerve fibres in
      the anterior pituitary of normal and adrenalectomized rats. The results showed
      only a small amount of galanin-like immunoreactive nerve fibres in the normal
      anterior pituitary, which were present among the gland cells as well as along the
      blood vessels. Following adrenalectomy, the number of galanin-like immunoreactive
      nerve fibres increased and ramification appeared more frequently. The results
      substantiate our hypothesis of a dual neural-humoral regulation of the mammalian
      anterior pituitary gland.

PMID- 9587625
TI  - Changes in the synaptology of spinal motoneurons in zebrafish following spinal
      cord transection.
AB  - Effects of spinal cord transection on the synaptology of zebrafish spinal
      motoneurons were studied. The transection was made at the level of the 14th
      vertebra and the synaptology of motoneuron somata and dendrites was analysed at
      the level of the 21st to the 23rd vertebrae at one month and three months after
      transection. Horseradish peroxidase, applied to the myotomal muscle, was used to
      label motoneuron somata and dendritic branches in central and in lateral areas of
      the neuropil (referred to as central and lateral dendritic profiles). Boutons
      impinging on motoneurons were classified according to the morphology of the
      vesicles. We discerned R-boutons with spherical vesicles, F-boutons with flat
      vesicles and DC-boutons with at least one dense core vesicle. The apposition
      lengths of R-, F- and DC-boutons and the circumference of labelled profiles were
      determined to assess the proportional covering of boutons on somata and
      dendrites. Ratio's of covering with R- and F-boutons (R/F ratio) for somata,
      central and lateral dendritic profiles were 1.1, 2.1, and 2.1 in control fish and
      0.5, 0.5 and 0.9 in lesioned fish at one month after transection, respectively.
      The total covering of motoneurons in lesioned fish was decreased by 20% on somata
      and by 30% on lateral dendritic profiles, whereas central dendritic profiles did
      not change significantly. At three months after transection the R/F ratio's for
      somata, central and lateral dendritic profiles were 0.5, 0.7 and 0.6,
      respectively. The total covering on somata and central and lateral dendritic
      profiles was at control levels. The anatomical aspects of the changes in
      synaptology indicate that in control fish 50 to 60% of the R-boutons on the
      motoneuron surface originate from descending axons. In contrast, almost all F
      boutons seem to be from local origin.

PMID- 9587627
TI  - Expression patterns of the ectopeptidases aminopeptidase N/CD13 and dipeptidyl
      peptidase IV/CD26: immunoultrastructural topographic localization on different
      types of cultured cells.
AB  - Aminopeptidase N/CD13 and dipeptidyl peptidase IV/CD26 are widespread membrane
      bound peptidases involved in fundamental biological processes. Using cryo
      ultramicrotomy of cultured cells followed by indirect immunogold labelling, both
      enzymes appeared to be strongly and regularly labelled on the cell surfaces of
      human synovial fibroblasts, T-lymphocytes and colon carcinoma cells Caco-2. In
      the cytoplasm of the synovial fibroblasts gold-labelled vesicle-like structures
      were found, which we consider to be potential transport vesicles. An abundant and
      regular expression of CD13 was detected on cultured renal parenchymal cells. On
      the renal carcinoma cell line Caki-1 cells we found a low, non-homogeneous and
      clustered CD13-labelling. On cultured renal parenchymal cells and the Caki-1
      cells CD26 could not be observed. The expression pattern of CD26 on renal
      carcinoma cell line Caki-2 cells showed also a slightly clustered distribution. A
      low density CD26-labelling was present on the squamous cell carcinoma cell line
      UM-SCC-22B. CD13 was absent in Caki-2 and UM-SCC-22B cells. The presence of both
      enzymes on the cultured cells enables their ultrastructural investigation under
      different growth conditions and their involvement in cell-cell interactions. For
      this purpose, however, further investigations are necessary.

PMID- 9587628
TI  - Reactive oxygen species (ROS) generated by xanthine oxidase in the corneal
      epithelium and their potential participation in the damage of the corneal
      epithelium after prolonged use of contact lenses in rabbits.
AB  - Prolonged use of contact lenses (for 14 days) evoked an imbalance between the
      activity of xanthine oxidase (an enzyme belonging to reactive oxygen species
      generating oxidases) and catalase (an enzyme belonging to reactive oxygen species
      scavenging oxidases) in the corneal epithelium of rabbits. The activity of
      catalase decreased, while xanthine oxidase activity was very high. Of other
      enzymes studied in the corneal epithelium, the activities of xanthine
      oxidoreductase, glucoso-6-phosphate dehydrogenase and succinate dehydrogenase
      were decreased. In contrast, the activities of lactate dehydrogenase and
      lysosomal hydrolases (acid beta-galactosidase, dipeptidyl peptidase II) were
      increased and appeared in animals sacrificed immediately after contact lens
      removal. In rabbits sacrificed later (after 1 h), an additional increase of
      lactate dehydrogenase and lysosomal hydrolase activities developed in the
      superficial layers of the corneal epithelium. Catalase supplementation during use
      of contact lenses prevented both the significant decrease of catalase activity in
      the corneal epithelium and the development of additional epithelial damage. In
      contrast, topical treatment with 3-aminotriazole (an inhibitor of catalase)
      resulted in the nearly complete loss of catalase activity in the corneal
      epithelium and the appearance of more serious epithelial damage. We conclude that
      ROS generated by xanthine oxidase induce additional damage of the corneal
      epithelium related to the use of contact lenses.

PMID- 9587629
TI  - Immunoreactive TSH cells in the pituitary of female middle-aged rats after
      treatment with estradiol or calcium.
AB  - The pituitary TSH cell structure of middle-aged (14-month-old) female Wistar rats
      chronically treated with estradiol dipropionate (EDP), calcium glucoheptonate
      (Ca) or with the combination of both was studied. TSH-producing cells were
      examined in the pituitary pars distalis using rabbit anti-rat beta-thyrotropin
      (TSH) serum and peroxidase-antiperoxidase immunohistochemistry. A stereological
      method for the determination of morphometric changes of the volume of TSH cells
      and nuclei as well as of their number and relative volume densities was used. All
      examined morphometric parameters in treated animals showed a significant decrease
      in comparison with immunoreactive TSH cells of the controls; the most significant
      decrease was observed in EDP-treated rats. These results together with structural
      features of immunoreactive TSH cells in the pituitary of middle-aged rats after
      chronic application of EDP or Ca indicate that both compounds inhibit these
      cells.

PMID- 9587630
TI  - Accessing the embryo interior without microinjection.
AB  - For decades it has been assumed that in order to insert macromolecules into the
      embryo blastocoel for numerous experimental purposes, microinjection was
      required. Microinjection, however, can be only performed on a few embryos at a
      time, thus precluding many studies that could involve large populations of
      embryos. Laser scanning confocal microscopy, with its optical sectioning
      advantage, showed that fluorochrome-labeled macromolecular lectins and bovine
      albumin enter the blastocoel of living, swimming sea urchin embryos following a
      period of incubation without microinjection. A procedure is also described that
      shows macromolecular entry is substantially accelerated in low calcium seawater.
      The information gained from this study should greatly facilitate experiments on
      entire populations of millions of embryos at a time that require access of
      macromolecules to the embryo interior.

PMID- 9587631
TI  - Intercellular adhesion molecule-1 (ICAM-1), leucocyte function-associated antigen
      1 (LFA-1) and leucocyte infiltration in proliferative human glomerulonephritis.
AB  - The expression of the intercellular adhesion molecule-1 (ICAM-1), infiltrating
      cells positive for its ligand leucocyte adhesion molecule-1(LFA-1), and the
      markers of total leucocytes (CD45RB), T cells (CD45RO), and monocytes/macrophages
      (CD68) were examined by an indirect immunoperoxidase method on renal biopsy
      specimens from 20 patients with mesangial proliferative glomerulonephritis-IgA
      negative (MesProGN) and 20 with IgA nephropathy (IgAN). Histologically, normal
      portions of the kidney tissue (n = 15) obtained from patients with renal trauma
      or renal tumours were used as controls. The expression of ICAM-1 was evident and
      extended in mesangium, on endothelial cells of peritubular capillaries,
      interstitial cells, several infiltrating immune cells and on tubular epithelial
      cells, particularly on atrophic tubuli in renal biopsies of MesProGN and IgAN. In
      both types of glomerulopathies a significant increase in the number of glomerular
      and interstitial LFA-1-positive cells correlated positively with the expression
      of ICAM-1. The number of glomerular and interstitial LFA-1-positive cells
      correlated positively with the number of monocytes/macrophages in glomeruli and
      interstitium. The strong correlation between expression of ICAM-1 and LFA-1 and
      between LFA-1-positive cells and immune cells makes these adhesion molecules
      useful markers of activity and suggest that they are involved in recruitment of
      leucocytes in the studied types of proliferative glomerulopathies.

PMID- 9587632
TI  - The acidophilic nature of neuronal Golgi impregnation.
AB  - The mechanisms of Golgi impregnation of neurons has remained enigmatic for
      decades. Recently, it was suggested that divalent (di)chromate anions play a role
      in the Golgi impregnation process. Therefore, we incubated slices of
      (para)formaldehyde-fixed rat brain tissue in solutions of potassium (di)chromate,
      phosphate, chloride or nitrate at pH 6 or 7. Slices were then immersed in
      solutions of silver nitrate and processed for light microscopical analysis. At pH
      6, dichromate probes resulted in dense and homogeneous impregnation of neuronal
      cytoplasm (typical impregnation). At pH 7, chromate probes showed solely partial
      cytoplasmic and heavy nuclear-region neuron impregnation (atypical impregnation).
      Phosphate probes at pH 6 resulted in typical impregnation, whereas at pH 7
      phosphate probes gave atypical impregnation. Both at pH 6 and 7, chloride and
      nitrate probes did not yield any Golgi impregnation. These findings confirmed the
      pH-dependence of silver-chromate Golgi impregnation as well as the correctness of
      corresponding acidic silver-phosphate impregnation. Our study revealed a
      previously unknown, strong anion-dependence of Golgi impregnation, suggesting
      that hydrogenated monovalent anions are carriers of the neuron impregnation.

PMID- 9587633
TI  - The Golgi architecture and some EM observations on the avian nucleus
      dorsolateralis anterior thalami: cell types, fibres and synapses.
AB  - In Golgi preparations of the chicken diencephalon, various types of cells and
      fibres were studied in the nucleus dorsolateralis anterior thalami (DLA). Two
      groups of neurons were found: projection neurons with long axons and interneurons
      with locally branching axons. The projection neurons varied in the different
      areas of the DLA. In the medial part the neurons are large cells with long,
      moderately spiny dendrites, and in the dorsal part there are small cells with
      short, wavy and moderately spiny dendrites. These neurons differ completely from
      those found in the rostral and lateral parts, where the neurons have medium-sized
      cell bodies and curving, spiny dendrites, which branch tuft-like or with
      bifurcations. In the rostral and lateral parts of the DLA, thick afferent fibres
      were impregnated which developed their terminal branchings among the neurons.
      Owing to their terminal branching pattern and the shape of the terminals they are
      thought to be optic fibres. The terminal pattern of these fibres is similar to
      the optic terminals in the LGB of the mammalian brain. The interneurons are GABA
      positive, as attested by immunostaining in light microscopic and EM specimens.
      There are rather few of them. The HRP-filled projection neurons and the
      surrounding neuropil were investigated under EM: synaptic connections around the
      large terminals and/or around dendrites were identified, but this synaptic
      arrangement does not display the characteristics of a synaptic glomerulus.

PMID- 9587634
TI  - Sequential order of appearance of ossification centers in the opossum Didelphis
      albiventris (Didelphidae) skeleton during development in the marsupium.
AB  - Pouch-young of the opossum Didelphis albiventris were studied. They were removed
      from the marsupium at a crown-rump length (CRL) of 9.0 to 100.0 mm and submitted
      to differential staining of the bone and cartilage. Newborn D. albiventris of 9.0
      to 10.0 mm CRL have a cartilaginous skeleton, with no macroscopic evidence of
      ossification. In 10.5 to 13.0 mm CRL pouch-young, ossification occurs in the
      bones surrounding the oral cavity, clavicle, ribs, cervical and thoracic
      vertebrae and thoracic limbs, structures necessary to ensure the survival and
      maintenance of the newborn in the marsupium. Ossification of most of the skull
      begins in 15.5 to 16.0 mm CRL pouch-young. The ossification in the pelvis and the
      pelvic limbs is observed at 18.0 mm CRL and in the sternum and the epipubic bone
      at 25.0 to 28.0 mm CRL. Most of the skeleton is ossified in 45.0 to 58.0 mm CRL
      pouch-young, except in the carpus, tarsus and epiphyses of the long bones where
      ossification occurs in 60.0 to 100.0 mm CRL pouch-young. In the skeleton of D.
      albiventris the omosternum, haemal arches, prepollex, prehallux and parafibula,
      are present. These are inconstant or absent elements in eutherian mammals.

PMID- 9587635
TI  - [Genesis and significance of so-called asphyxial infiltrates in the placenta. I.
      Histologic results].
AB  - The conventional conception of the cause and formal pathogenesis of so-called
      "asphyxial infiltrates" of the placenta is presented. Morphological examples are
      given. Our study included 561 newborn cases. Eighty two cases (14.6%) had such
      cell infiltrates, and there were 6 cases with phlegmoneous inflammation of the
      fetal membranes. These morphological findings correlated with the following
      clinical characteristics: term of birth, weight classes of newborns, Clifford
      signs, clinical risks with respect to hypertension, the course of pregnancy and
      particularly the risk of inflammation. Additional correlates were the clinical
      statement of hypoxia and acidosis in newborns. We discovered relationships
      between these cell infiltrates and the Clifford-signs, and to some clinical risks
      (especially those for inflammation), but not to hypoxia and acidosis of the
      newborn. Our results show, that there are no relations between the conventional
      "Asphyxial infiltrates" of the placenta and the hypoxia and acidosis observed in
      newborns.

PMID- 9587637
TI  - A scanning electron microscopy study of peritoneal stomata in different
      peritoneal regions.
AB  - Peritoneal stomata constitute the principal pathways for the drainage of
      intraperitoneal contents from the peritoneal cavity to the lymphatic system and
      have been claimed to be exclusively restricted to the peritoneal surface of the
      diaphragm. This concept has been revised by the demonstration of peritoneal
      stomata in the omental, mesenteric, ovaric and pelvic peritoneum. Therefore, the
      aim of this study was to further assess peritoneal surfaces of several other
      abdominal organs and of the abdominal wall with special reference to the
      occurrence of peritoneal stomata. The peritoneum covering the spleen, stomach,
      intestine, liver, diaphragm and anterior abdominal wall obtained from rats was
      examined by scanning electron microscopy. Whereas the splenic and hepatic
      peritoneal surfaces were composed of uniformly distributed cuboidal mesothelial
      cells, the gastric and intestinal peritoneal surfaces were arranged in parallel
      folds composed of prominent mesothelial cells with elongated finger-like
      cytoplasmic processes. In addition to diaphragmatic peritoneal stomata,
      mesothelial openings were also found on the peritoneal surfaces covering the
      anterior abdominal wall and the liver. The parietal peritoneal stomata were
      arranged in clusters, oval in shape and delimited by flattened mesothelial cells
      exposing the underlying submesothelial connective tissue. The hepatic mesothelial
      openings formed by deep channel-like gaps of adjacent cuboidal mesothelial cells
      were almost completely occluded by a dense microvillous coat. As the
      submesothelial connective tissue was not identifiable with certainty, the
      mesothelial openings were regarded as corresponding to stoma-like structures.
      These findings yield further evidence that peritoneal stomata are obviously not
      confined to the diaphragmatic area but extend to other peritoneal regions. It is
      therefore suggested that these extra-diaphragmatic parietal and visceral
      peritoneal surfaces contribute to the absorption capacity of the entire
      peritoneum and are subsequently involved in either therapeutic procedures or
      pathological processes affecting the peritoneal cavity.

PMID- 9587636
TI  - Treatment of pregnant females with dexamethasone influences postnatal development
      of the adrenal medulla.
AB  - In the light of the mutual dependence between the adrenal cortex and medulla, the
      aim of this work was to examine whether glucocorticoid treatment of pregnant rats
      affects the development of the adrenal medulla of their offspring in the
      postnatal period. Pregnant rats were treated with dexamethasone (Dx) in a daily
      dose of 0.3 mg Dx/kg b.w. during days 16-20 of gestation. The structure and
      function of the adrenal medulla of their 14-day-old offspring were estimated on
      the basis of the morphometric parameters of the gland, chromaffin cell mitotic
      index and adrenal gland adrenaline content. Stereological analysis was carried
      out at the light microscopic level, the mitotic index was determined by counting
      the number of metaphase arrested chromaffin cells following the administration of
      vincristine-sulphate, whereas adrenaline content in the adrenal gland was
      measured fluorimetrically. Plasma ACTH concentrations of the offspring were also
      determined by RIA. Long term Dx treatment of pregnant rats caused a significant
      decrease of the total volume of adrenal chromaffin tissue in the 14-day-old
      offspring as well as a reduction in the number of chromaffin cells and the
      average cell and nuclear volumes. The proliferative activity of the chromaffin
      cells was also lower than in the control offspring. These changes were
      accompanied by a significantly reduced adrenaline content in the adrenals. The
      results of this work show that glucocorticoid excess during the period of
      pregnancy when the fetal adrenal medulla is formed has a strong inhibitory effect
      on the adrenal medulla of the offspring at the age of 14 days.

PMID- 9587638
TI  - The autonomous innervation of the porcine testis in the period from birth to
      adulthood.
AB  - The innervation of the porcine testis was studied in 20 pigs, aged from 3 days to
      2.5 years, and revealed remarkable changes in the period from birth to adulthood.
      Testes in piglets of 3 to 5 weeks have the most intense and most constant
      innervation, which reaches the gonad by three different routes: the funicular,
      caudal and mesorchial. Nerve fibers supply the vascular structures of the
      spermatic cord, the tunica albuginea, nearly all the septula testis and the
      mediastinum. Only exceptionally are axons in contact with Leydig cells. Nearly
      all the testicular nerves are positive for DBH and therefore represent
      postganglionic sympathetic axons. From their association with blood vessels it
      can be concluded that the majority of nerves are vasomotor in function. No
      cholinergic and myelinated fibers can be detected in the porcine testis. NPY
      immunoreactive fibers are the dominating peptide-containing neuronal component.
      In the testes of 3- and 7-day-old piglets the degree of septal and mediastinal
      innervation is significantly smaller than in 3- to 5-week-old animals. In 7- to
      10-week-old pigs, testicular innervation shows varying degrees of withdrawal, and
      the testes of adult boars are completely devoid of intrinsic nerves. Only the
      funicular nerves supplying the testicular artery and pampiniform plexus are
      preserved in the adult age group. So, the vasomotor control of intratunical,
      septal and mediastinal vessels and of the complete micro-circulation within the
      testicular parenchyma is effected without any direct nerve participation in the
      sexually mature boar.

PMID- 9587639
TI  - Immunohistochemical localization of neurotrophins and neurotrophin receptors in
      human and mouse salivary glands.
AB  - This study was undertaken to analyze the occurrence of low- (p75) and high
      affinity (TrkA, TrkB and TrkC) neurotrophin receptor proteins in human and mouse
      salivary glands using immunohistochemistry. Furthermore, the presence of
      neurotrophins was also investigated. The study was carried out on 14 human (4
      parotid, 6 submandibular and 4 sublingual glands) and 5 mouse salivary glands,
      using polyclonal antibodies against Trk proteins. The intensity of immunostaining
      was calculated automatically and evaluated in arbitrary units of grey levels. In
      human tissues no immunoreactivity (IR) for the assessed antigens was observed in
      the serous or mucous acinar cells, although TrkA IR was found in the acini of the
      submandibular gland. The cells of the intercalated ducts showed p75 IR
      (sublingual) and TrkA IR (parotid gland). The striated and excretory ducts
      displayed p75 IR, TrkA IR and TrkC IR in all glands, but TrkB IR was never
      detected. No neurotrophins were detected. In the mouse glands the ductal cells
      display IR for p75 (submandibular) and Trks A and C (parotid and submandibular)
      but not the sublingual gland. Acinar cells of the submandibular gland also show
      p75 IR. The only neurotrophin found in the mouse salivary glands was NGF
      (submandibular gland). These results suggest that neurotrophins may be involved
      in controlling the physiology of epithelial salivary cells.

PMID- 9587640
TI  - The size of sebaceous glands in relation to the size of hair follicles on the
      heads of some small mammals (Insectivora, Chiroptera, Rodentia).
AB  - Many large sebaceous glands have been described, and functions such as scent
      production suggested, but gland size has seldom been studied in relation to the
      surface area of their hair follicles. However, investigating this relationship is
      essential for establishing whether glands produce more sebum than would be
      required for lubricating associated hair alone. Here, the relationship between
      sebaceous gland size and the surface area of the associated hair follicles has
      been studied. Glands on the heads of 20 species from three orders were compared
      with those associated with fur hairs. In all species, the fur hairs had small
      hair follicles with small sebaceous glands, as had the mystacial and
      submandibular hairs of Rodentia. Medium-sized glands and hairs were found in the
      mystacial and submandibular region in Insectivora, and in the circumoral region
      in Chiroptera and Rodentia. Large glands and hairs were found on a pad in the
      corner of the mouth in Rodentia. Although the size of glands was not directly
      proportional to hair size, some gross trends were noted. Vibrissae had either no
      or very small sebaceous glands. It is likely that sebum has to be provided from
      elsewhere to lubricate their surfaces. The glands on the snout of Insectivora and
      Chiroptera are clearly enlarged and could probably produce more sebum than would
      be required for grooming vibrissae alone. In Rodentia, vibrissae were surrounded
      by small hair and glands, and the nearest glands large enough to provide sebum
      were the glands on the pad in the mouth corner.

PMID- 9587641
TI  - Comparative structural analysis of neuromuscular junctions in mice at different
      ages.
AB  - The authors studied the histochemical and ultrastructural modifications that
      occur in the neuromuscular junctions (NMJ) of fibularis longus muscles of mice
      with an age range of 3 to 21 months. Twenty-four male and female animals were
      killed at 3, 5, 14 and 21 months of age: 7 of them at 3 months, 4 of them at 5
      month, 9 at 14 months and 4 at 21 months. The fibularis longus muscles were
      processed and their NMJ examined with the transmission electron microscope. The
      most relevant changes were associated with the degeneration and retraction of
      terminal axons, i.e., axons poor in synaptic vesicles with degenerated
      mitochondria, and exhibiting multivesicular bodies and vacuoles; exposed and
      widened junctional folds and cytoplasmic processes of Schwann cells located in
      the synaptic gutter. The presence of lysosomes or lipofuchsin in the
      juxtajunctional sarcoplasm was also noted. These observations suggest that the
      phenomena of retraction and budding occur in the NMJ with advancing age, with a
      predominance of events associated with degeneration, leading to profound changes
      in NMJ shape.

PMID- 9587642
TI  - Origin and regional distribution of the arterial vessels of the vomeronasal organ
      in the sheep. A methodological investigation with scanning electron microscopy
      and cutting-grinding technique.
AB  - The origin and location of the arteries of the vomeronasal organ (VNO) in the
      sheep were studied by means of dissection, scanning electron microscopy of
      corrosion casts, and the cutting-grinding technique after injection with Araldite
      CY23-HY2967 via one of the carotid arteries. Dissection revealed that the most
      ventral of the three main branches of the sphenopalatine artery is responsible
      for the blood supply to the VNO. Scanning electron microscopy of corrosion casts
      revealed that the arterioles of the vomeronasal organ form a microvascular
      network. Cross sections of the region of the nasal cavity containing the VNO,
      obtained by the cutting-grinding technique, showed that the arterioles of the
      vomeronasal plexus are located medial and ventral to the vomeronasal duct. These
      results confirm the usefulness of the cutting-grinding technique as a
      complementary procedure in morphological studies of structures containing hard
      tissues.

PMID- 9587643
TI  - The intima: historic literature revisited.

PMID- 9587644
TI  - Effects of cholecystectomy on gastric emptying and myoelectrical activity in man.
AB  - To investigate the effects of cholecystectomy on gastric motor function, 13
      patients with symptomatic gallstones were studied before and 8-12 months after
      surgery. Twelve healthy subjects entered the study as control group. The
      cutaneous electrogastrography and ultrasound examination of gastric emptying were
      simultaneously performed at pre- and post-prandial states. The dominant gastric
      frequency and its coefficient of variation were not affected by surgery. After
      cholecystectomy, an increase in normal 3 cpm wave percentage and a decrease in
      power ratio were found (P < 0.05 and P < 0.01, respectively). Gastric emptying
      recorded after cholecystectomy was faster than before surgery (306.9 +/- 15.9 min
      vs 336.9 +/- 11.8 min, respectively; P < 0.05). Such changes were associated with
      the relief of symptoms, and the comparison between patients and controls showed a
      normalization of the gastric electrical activity and gastric emptying after
      surgery. In conclusion, in symptomatic patients, gallstones are associated with
      motor dysfunctions, and cholecystectomy seems to induce a normalization of
      gastrointestinal motility.

PMID- 9587645
TI  - Effects of bilateral olfactory bulbectomy on circadian rhythms of ACTH,
      corticosterone, motor activity and body temperature in male rats.
AB  - Bilateral olfactory bulbectomy (BOX) has major biochemical and behavioral
      effects, and is one of the most widely investigated of animal models of
      depression. We studied the consequences of BOX in male rats, on the organization
      of endogenous circadian rhythms for ACTH, corticosterone (Cort), motor activity
      (MA) and body temperature (BT). Mean levels were increased for Cort and MA,
      whereas no significant changes were observed for ACTH and BT. Significantly
      higher plasma Cort morning values were evidenced in BOX than sham-operated
      animals. In addition, compared with the single prominent power spectrum for the
      24 hours period of control rats, the BOX animals displayed substantially lower 24
      hours spectral power for the MA and BT circadian rhythms. These alterations
      suggest that olfactory bulbectomy, by disruption of the afferences and
      efferences, induced drastic changes in the function of the endogenous clock or of
      its regulating systems. From this point of view, bulbectomized rats may therefore
      be a valuable model to studying the etiology of psychiatric disorders with rhythm
      disturbance.

PMID- 9587646
TI  - Changes in the nucleolar organizer regions in the tuberomammillar region after
      dehydration.
AB  - The existence of efferent connections between tuberomammillary (TM) and the
      supraoptic (SON) nuclei led us to study the morphological changes at these levels
      during dehydration induced in rats by repeated administration of hypertonic
      saline. The dehydration effects are evaluated by three parameters: nucleus area,
      argyrophilic nucleolar organizer regions (Ag-NOR) area, and mean number of Ag
      NORs. These parameters reflect the level of transcriptional activity of the rRNA
      genes, which in turn is closely related to the protein synthesis activity of the
      cell. The technique used is argyrophilic staining which labels the nucleolar
      organizer regions (NORs) of the nucleoli in the neurons and their area,
      permitting their quantification with an image analysis system. The statistical
      analysis reflects the sensitivity to dehydration of these structures at TM level.
      Our results support the regulatory role of vasopressin secretion by SON through
      the histaminergic pathways arising from TM in rat dehydration processes.

PMID- 9587647
TI  - Regulation by diet of the pancreas enzyme content of suckling goats.
AB  - To study pancreas enzyme content regulation when the diet was modified in
      suckling goats, a comparison was made between kids fed a milk replacer and ones
      fed maternal milk. A total of 25 preruminant Granadina breed goats were bottle
      fed a milk replacer ad libitum from postnatal days 3 to 28 (until the age of 3
      days kids had been fed colostrum). Body weight, pancreas weight, total protein
      concentration, and enzyme activities in pancreatic tissue were determined at 3,
      7, 14, 21 and 28 days of age, and the results were compared to those previously
      obtained in kids fed maternal milk for the same period. Lipase activity was
      significantly lower in the group fed milk replacer, which was poorer in fat.
      Amylase activity was higher in this group, perhaps due to the starch products
      present in the milk substitute. However, the postnatal evolution of chymotrypsin
      activity followed a similar pattern regardless of diet. Our results seem to
      confirm that in preruminant kids there is a nutritional regulation of pancreatic
      amylase and lipase activities, depending on the amounts of their respective
      substrates in the diet, similar to that described in nonruminants.

PMID- 9587648
TI  - Effects of fasting, hypoxia, methylpalmoxirate and oxfenicine on the tissue
      levels of long-chain acyl CoA and acylcarnitine in the rat atria.
AB  - During hypoxia the atria from fasted rats exhibit a faster decline in the
      pacemaker and contractile activities than those from fed rats. Oxfenicine and
      methylpalmoxirate, inhibitors of carnitine palmitoyltransferase 1 (CPT 1),
      ameliorate these disturbances. Since the fasted rat atria have greater
      triacylglycerol stores and a faster lipolysis, and CPT 1 funnels fatty acid into
      beta-oxidation, the effects of fasting could be ascribed to the accumulation of
      amphipathic metabolites such as long-chain acyl CoA (LCCoA) and long-chain
      acylcarnitine (LCCa). Hence, this investigation aimed to assess whether the
      levels of these metabolites correlate with the effects of fasting and CPT 1
      inhibitors. At the end of the prehypoxic equilibration period the fasted rat
      atria had a 6.5-fold greater content of LCCa than those of the fed rats and
      methylpalmoxirate impeded the increase. During hypoxia the LCCoA content
      increased 9-fold in the fasted rat atria, LCCa levels were 3.6-fold greater in
      the fasted than in the fed group, and free-CoA and free-carnitine showed a
      significant fall. The increases of LCCoA and LCCa as well as the fall in free-CoA
      were abolished by both inhibitors. The decrease of free-carnitine was impeded by
      methylpalmoxirate, but oxfenicine unexpectedly decreased its concentration in
      both nutritional groups. These data suggest that: (1) the atrial CPT 1 activity
      is enhanced during fasting, (2) in the hypoxic atria levels of LCCoA and LCCa
      were closely correlated with the noxious effects of fasting and the amelioration
      effected by CPT 1 inhibitors, and (3) the effects of amphipathic metabolites
      during oxygen deprivation can be attenuated by pharmacological interventions.

PMID- 9587649
TI  - Influence of angiotensin II on transmission in the superior cervical ganglion.
AB  - The influence of angiotensin II (ANG II) on sympathetic ganglionic transmission
      was examined in the in situ, normally perfused, superior cervical ganglion in
      pentobarbitone-anaesthetized rabbits. Compound action potentials were evoked in
      the external carotid nerve by repetitive electrical stimulation of the
      decentralized preganglionic cervical sympathetic nerve (supramaximal intensity, 1
      ms, 0.5 Hz). A continuous partial nicotinic block was maintained by intravenous
      infusion of hexamethonium. The converting enzyme inhibitor captopril was infused
      to prevent the endogenous generation of ANG II. Graduated intravenous infusion of
      ANG II brought about graduated increases in the height of the S2 potential; the
      threshold rate of infusion for this effect was 40 ng min-1. At this infusion
      rate, the plasma concentration of ANG II was estimated to lie between 80 and 600
      pg ml-1. While ANG II can modify sympathetic ganglionic transmission, it is
      unlikely that it has any effect at physiological plasma concentrations of
      circulating ANG II reported for the rabbit (2-80 pg ml-1).

PMID- 9587650
TI  - Biomechanical events in the time to exhaustion at maximum aerobic speed.
AB  - Recent studies reported good intra-individual reproducibility, but great inter
      individual variation in a sample of elite athletes, in time to exhaustion (tlim)
      at the maximal aerobic speed (MAS: the lowest speed that elicits VO2max in an
      incremental treadmill test). The purpose of the present study was, on the one
      hand, to detect modifications of kinematic variables at the end of the tlim of
      the VO2max test and, on the other hand, to evaluate the possibility that such
      modifications were factors responsible for the inter-individual variability in
      tlim. Eleven sub-elite male runners (Age = 24 +/- 6 years; VO2max = 69.2 +/- 6.8
      ml kg-1 min-1; MAS = 19.2 +/- 1.45 km h-1; tlim = 301.9 +/- 82.7 s) performed two
      exercise tests on a treadmill (0% slope): an incremental test to determine VO2max
      and MAS, and an exhaustive constant velocity test to determine tlim at MAS.
      Statistically significant modifications were noted in several kinematic
      variables. The maximal angular velocity of knee during flexion was the only
      variable that was both modified through the tlim test and influenced the exercise
      duration. A multiple correlation analysis showed that tlim was predicted by the
      modifications of four variables (R = 0.995, P < 0.01). These variables are
      directly or indirectly in relation with the energic cost of running. It was
      concluded that runners who demonstrated stable running styles were able to run
      longer during MAS test because of optimal motor efficiency.

PMID- 9587651
TI  - Erythromycin elicits opposite effects on antro-bulbar and duodenal motility:
      analysis in diabetics by cineradiography.
AB  - We have previously demonstrated by cineradiography analysis that erythromycin
      (Ery) increases antral contractility and antropyloric coordination in diabetics.
      The aim of this study was to further characterize antro-bulbar and duodenal
      motility after Ery i.v. administration. Fourteen diabetic patients (mean age 61.2
      years) were randomly allocated to receive either 100 or 500 mg of Ery
      intravenously 4 hours after a standard solid liquid meal. After ingestion of a
      barium sulfate suspension, a series of 15 fluorographic plates (one every two
      seconds) was performed. the same procedure was repeated twice for each subject
      with a delay of 3 days once before and once after Ery. Antral, bulbar and
      duodenal areas and evolution diagrams were calculated in baseline conditions and
      after Ery administration using a graphic table connected to a microcomputer. No
      differences were found between the two doses of the drug. Ery significantly
      decreased antral (1284 +/- 268 mm2 vs 704 +/- 181 mm2; P < 0.01) and bulbar areas
      (127 +/- 26 mm2 vs 73 +/- 21 mm2; P < 0.01). In contrast, duodenal areas were
      significantly increased after Ery (875 +/- 112 mm2 vs 575 +/- 112 mm2; P < 0.01).
      This study suggests that the known prokinetic effect of Ery on gastric emptying
      seen in diabetic patients could be related to an increase of motility in the
      antrum and in the bulb simultaneously with a relaxation in the duodenum.

PMID- 9587652
TI  - Cyclosporin A stimulates Na+ transport across the isolated skin of Rana
      esculenta.
AB  - Cyclosporin A (Cs A), added to the fluid bathing the internal surface of the
      isolated skin of Rana esculenta, increased short-circuit current (SCC) with a
      maximal effect at 5 microM. This effect was completely inhibited by amiloride
      (0.2 mM in the fluid bathing the external surface). By measuring both
      transepithelial fluxes of 22Na+ across symmetrical parts of the short circuited
      skin, Cs A was found to increase the net absorption of Na+. Naproxen (10 microM),
      a cyclooxygenase inhibitor, decreased the stimulation by Cs A of SCC, suggesting
      that in this stimulation prostaglandins are involved. The Cs A effect on Na+
      transport could be caused by an inhibition of a Ca2+/calmodulin-dependent protein
      phosphatase, i.e. calcineurin, since: a) it is mimicked by another inhibitor of
      calcineurin, i.e. fenvalerate: b) the action of Cs A and fenvalerate on SCC are
      decreased by the calmodulin inhibitor W7.

PMID- 9587653
TI  - Effect of diet induced hypercholesterolemia and selenium supplementation on
      nitric oxide synthase activity.
AB  - The aim of the present study was to examine the activity of nitric oxide synthase
      (NOS, EC 1.14.23) in plasma of high fat diet (HFD, 2% cholesterol and 100 g table
      butter/kg diet) and HFD + selenium (Se, 1 ppm as sodium selenite) fed rabbits for
      three months. Significant increase in the serum cholesterol and triglyceride
      levels in HFD fed group was observed. The activity of NOS also increased very
      significantly. However in Se supplemented animals, there was a significant
      reduction in serum cholesterol as well as in plasma NOS activity relative to HFD
      fed animals. It is concluded that the protective effect of Se on HFD induced NOS
      activity acts probably through its antioxidant/inhibitory action.

PMID- 9587654
TI  - Lipid changes in hepatic microsomes and its relationship to P-nitrophenol
      glucuronidation in an experimental model of portal hypertension.
AB  - The liver is responsible for the most important metabolic pathway of non polar
      compounds. The aim of the present work was to study the p-nitrophenol
      glucuronidation and its relationship with lipidic composition of microsomal
      membrane in a model of hepatic portal hypertension and hepatocellular damage
      induced by monocrotaline. A global increment in liver microsomal phospholipids as
      well as changes in the phospholipid pattern (phosphatidylethanolamine and
      sphingomyelin increased up to 156 +/- 13 and 195 +/- 14% respectively) were
      detected in monocrotaline intoxicated rats when it were compared to control rats.
      The microsomal cholesterol content showed a decrease in monocrotaline intoxicated
      rats. (4.1 +/- 0.7 against 6.6 +/- 1.5 micrograms/mg of microsomal protein, in
      control rats). When p-nitrophenol activity was measured, Km from monocrotaline
      intoxicated rats was 0.137 mM, and Vmax was 2.9 nmol of p-nitrophenol/mg
      microsomal protein since in control group Km was 0.322 mM, and Vmax was 4.5 nmol
      of p-nitrophenol/mg microsomal protein. It is concluded that monocrotaline
      intoxicated rats showed a different behavior in the kinetics of p-nitrophenol UDP
      glucuronyltransferase, as well as a different microsomal lipidic profile, when
      compared to control group.

PMID- 9587655
TI  - Isoform distribution of parvalbumins and of some myofibrillar proteins in adult
      and developing Chrysichthys auratus (Geoffroy St. Hilaire, 1808) (Pisces,
      Claroteidae).
AB  - Polyacrylamide gel electrophoresis was used to analyse the distribution of
      parvalbumin, myosin light chain, and troponin I isoforms in white muscles of
      larval, juvenile, and adult Chrysichthys auratus (catfish, siluriforms) and to
      study the kinetics of their synthesis. Parvalbumin isoform PA II was first
      detected from day 5 post-hatching and was the main "larval" isoform in this
      species. PA III appeared at the beginning of the juvenile stage but always
      remained the minor isoform, even in adult fish. Young mature specimens
      (approximately 12 cm long) displayed the highest total parvalbumin content. Adult
      type myosin light chains were detected from day 8. Densitometric analysis
      confirmed the light-chain distribution typical of fish muscles, with a relatively
      high amount of LC3 and a low amount of LC1. We evidenced a "larval" form of
      troponin-I and its progressive replacement by an "adult" form.

PMID- 9587657
TI  - In memoriam Paul Boulanger (21 November 1905-16 June 1996).

PMID- 9587659
TI  - Artificial fibrous proteins: a review.
AB  - Several kinds of natural fibrous proteins have been chosen as models: silk
      fibroin from Bombyx mori, silks from various species of spiders and collagens.
      The dragline silk of the spider Nephila clavipes is able to stretch by 30% before
      breaking and has a high tensile strength. It is stronger per unit weight than
      high tensile steel. Although the partial sequence of the two components of
      dragline silk is known, its molecular structure is still far from being clearly
      established. It is however demonstrated that it contains beta-sheet crystals
      composed of polyalanine residues. Artificial fibrous proteins have been prepared
      in vivo using either Escherichia coli or the yeast Pichia pastoris. As these
      proteins contain repetitive sequences, there is a risk of deletion at the DNA
      level. This difficulty has been solved by making use of the genetic code
      degeneracy. One group has successfully synthesized silk-like polymers; prolastin
      polymers containing both silk-like and elastin-like blocks; proNectin polymers
      containing the RGD triplet coming from fibronectin and able to fix numerous
      mammalian cell types; and synthetic collagen analogs. Some of these polymers have
      been spun into fibers that, up-to-now, do not display any measurable molecular
      orientation. Another group has studied artificial fibrous proteins able to form
      beta-sheet crystals of defined thickness and bearing functional groups at their
      surface, for instance Glu residues, selenomethionine or p-fluorophenylalanine.
      Apart from university laboratories, a venture capital society, an industrial
      research center and a US army research center are quite active in this field. A
      number of patents has been deposited.

PMID- 9587656
TI  - Energy dependence of protein synthesis by isolated cestode mitochondria.
AB  - Mitochondria of helminth parasites produce energy in a number of ways that vary
      from species to species, and, in general, do not possess a classical
      tricarboxylic acid (Krebs) cycle. The process of protein synthesis, which is
      energy dependent, is not well understood in this organelle. However, protein
      synthesis in helminth mitochondria seems to serve the purpose to the desired
      level despite its limited capacity to produce ATP compared to its mammalian
      counterpart. Data presented here demonstrate that helminth mitochondria can
      synthesize proteins in vitro and the process can be supported by energy supplied
      exogenously by the cytosol, by an ATP generating system utilizing a substrate
      such as malate, or by ATP itself.

PMID- 9587660
TI  - Conformational dynamics and enzyme activity.
AB  - Conformational flexibility and structural fluctuations play an important role in
      enzyme activity. A great variety of internal motions ranging over different time
      scales and of different amplitudes are involved in the catalytic cycle. These
      different types of motions and their functional consequences are considered in
      the light of experimental data and theoretical analyses. The conformational
      changes upon substrate binding, and particularly the hinge-bending motion which
      occurs in enzymes made of two domains, are analyzed from several well documented
      examples. The conformational events accompanying the different steps of the
      catalytic cycle are discussed. The last section concerns the motions involved in
      the allosteric transition which regulates the enzyme activity.

PMID- 9587661
TI  - Post-translational modification of proteins by reversible phosphorylation in
      prokaryotes.
AB  - Microorganisms have developed three different systems for catalyzing protein
      phosphorylation and using this reversible modificaiton to regulate their cellular
      activities. The first 'classical' system utilizes nucleoside-triphosphates as
      phosphoryl donors and leads to the modification of protein substrates at
      serine/threonine or tyrosine residues. The second system, called 'two-component
      system', requires first a sensor kinase which autophosphorylates at a histidine
      residue at the expense of adenosine-triphosphate, then a response regulator which
      is modified in turn at an aspartate residue and thereafter induces a metabolic
      change within the cell. The third system, called 'PTS system', makes use of
      phosphoenol pyruvate to generate a phosphoryl group which is passed down a chain
      of several proteins and finally transferred to a sugar. There is increasing
      evidence that, contrary to an early concept, these systems and the corresponding
      enzymes (protein kinases and phosphoprotein phosphatases) share a number of
      structural and functional similarities with the phosphorylation-dephosphorylation
      machineries found in eukaryotes. Therefore one can expect that microorganisms
      will serve, once again, as a basic model for exploring and understanding a key
      regulatory mechanism, reversible protein phosphorylation, which concerns all
      organisms.

PMID- 9587662
TI  - O-acetylation of sialic acids.
AB  - Sialic acids can be acetylated at the 4, 7, 8 and/or 9 position. Biological roles
      of these substitutions have been missed until recently because of their low
      abundance and lability to conventional purification methods. The recent advances
      in the analysis of sialic acids have allowed to demonstrate that O-acetylation
      has a selective but widespread distribution. The metabolism of acetylated sialic
      acids is under the control of two groups of enzymes, O-acetyl transferases and 9
      O-acetyl esterases. O-acetyl transferases are difficult to purify, and
      furthermore, attempts at expression cloning have failed in isolating the true 9-O
      acetyl transferase cDNA. This explains that the regulation of the selective
      expression of O-acetylated sialic acid in not completely understood. Acetylation
      of sialic acid is expressed on the outer most part of the carbohydrate moiety of
      membrane and secreted glycoconjugates. This particular location explains why this
      modification is involved in cell/cell interactions and in the non-immune
      protection of mucosa.

PMID- 9587663
TI  - 'Glyco-deglyco' processes during the synthesis of N-glycoproteins.
AB  - For the past 15 years, it has appeared increasingly evident that the N
      glycosylation process was accompanied by the release of oligomannoside type
      oligosaccharides. This material is constituted of oligosaccharide-phosphates and
      of neutral oligosaccharides possessing one GlcNAc (OS-Gn1) or two GlcNAc (OS-Gn2)
      at the reducing end. It has been demonstrated that oligosaccharide-phosphates
      originated from the cleavage by a specific pyrophosphatase, of non-glycosylated
      cytosolic faced oligosaccharide-PP-Dol and chiefly the Man5GlcNAc2-PP-Dol. The
      Man5GlcNAc2-P, as the main product, is recovered in the cytosolic compartment and
      is further degraded to Man5GlcNAc1 by as for yet not depicted enzymes. In
      contrast, OS-Gn2 produced from hydrolysis of oligosaccharide-PP-Dol (presumably
      as a transfer reaction onto water) when the amount of protein acceptor is
      limiting, are generated into the lumen of rough endoplasmic reticulum (ER). They
      are further submitted to processing alpha-glucosidases and rough ER mannosidase
      and are (mainly as Man8GlcNAc2) exported into the cytosolic compartment. This
      material is further degraded into a single component, the Man5GlcNAc1: Man alpha
      1-2Man alpha 1-2Man alpha 1-3 (Man alpha 1-6)Man beta 1-4GlcNAc by the sequential
      action of a cytosolic neutral chitobiase followed by cytosolic mannosidase.
      Furthermore, OS-Gn1 could have a dual origin: on the one hand, they originate
      from OS-Gn2 by the cytosolic degradation pathway indicated above; on the other
      hand, we will discuss a possible origin from the degradation or remodeling of
      newly synthesized glycoproteins. Considered first as a minor phenomenon, these
      observations have lead to the concept of intracellular oligomannoside
      trafficking, a process which results from more fundamental phenomena such as the
      control of the dolichol cycle, and the so-called quality-control of glycoprotein.
      In this review, we would like to describe the evolution of ideas on the origin,
      intracellular trafficking and putative roles of these oligomannosides released
      during the N-glycosylation process. We propose that these early stage 'glyco
      deglyco' processes represent a way of control of N-glycosylation and of the fate
      of N-glycoproteins.

PMID- 9587664
TI  - Polypeptide:N-acetylgalactosaminyltransferase activities towards the mucin MUC5AC
      peptide motif using microsomal preparations of normal and tumoral digestive
      mucosa.
AB  - The selected-acceptor substrate peptide (TTSAPTTS), deduced from the human mucin
      gene MUC5AC (expressed essentially in the human gastric and tracheobronchial
      mucosa), was used to assay polypeptide:N-acetylgalactosaminyltransferases (GalNAc
      transferases) of different microsomal preparations, obtained from gastric and
      colonic mucosa in normal and tumoral situations. The O-glycosylated products,
      analyzed by capillary electrophoresis and electrospray mass spectrometry, showed
      a variable number of GalNAc O-linked to the different hydroxy amino acids of
      TTSAPTTS, depending on the tissue studied. Our observations were consistent with
      the existence of more than one form of GalNAc transferases which were expressed
      differentially in the gastrointestinal tract (stomach and/or colon). The levels
      of enzyme activities showed a tissue-specific pattern as they were high in normal
      colonic tissue and low in colon cancer. On the other hand, in the tumoral gastric
      tissue (displaying intestinal metaplasia) a high level of GalNAc transferase
      activities was obtained, similar to that found in the normal colon. Moreover,
      slight discrepancies (activities and number of O-linked GalNAc) were only
      detected between normal gastric and tumoral colonic preparations. Thus, the data
      indicated that the dedifferentiation of the gastric cancer tissue may induce
      GalNAc transferase activities similar to those in the normal colonic, tissue and
      that colonic and gastric tissues may contain families of glycosyltransferases
      involved specifically in reaction towards particular peptide or protein
      substrates. In addition, the analysis by capillary electrophoresis and
      electrospray mass spectrometry revealed, in tumoral gastric as well as in normal
      colonic tissues, a high dipeptidylaminotransferase activity inducing an
      elongation of TTSAPTTS by dithreonine. This activity was low in normal gastric
      and tumoral colonic tissues.

PMID- 9587666
TI  - Purification of two lectins from a nopalin Agrobacterium tumefaciens strain.
AB  - Lectins were evidenced on the surface of one Agrobacterium tumefaciens wild
      strain (82,139) by agglutination test and neoglycoprotein labelling. Bacteria
      were incubated in the presence of various fluorescein-labelled neoglycoproteins
      and the binding was assessed by a fluorimetric method. Among the fluorescein
      labelled neoglycoproteins tested, the one bearing alpha-D-galactosyl residues was
      the most efficient. The labelling was optimal at pH 5.0 and naught at pH above 7.
      The binding was specifically inhibited by homologous fluorescein-free
      neoglycoproteins. A galactoside-specific lectin was purified to homogeneity by
      affinity chromatography on agarose-A4 substituted with alpha-D-galactopyranosyl
      residues. Upon polyacrylamide gel electrophoresis, a single band (M(r) 58,000)
      was detected. This alpha-D-galactoside-specific lectin agglutinated
      preferentially human B red blood cells at pH 5.0. Another lectin specific for
      alpha-L-rhamnoside (M(r) 40,000) not retained on the immobilised galactose was
      purified by affinity chromatography on alpha-L-rhamnosyl substituted agarose-A4.
      This L-rhamnoside-specific lectin preferentially agglutinated horse erythrocytes.
      On the basis of their M(r) and on their sugar specificity, these two lectins are
      novel lectins with regard to the known sugar-binding proteins present in the
      Rhizobiaceae family: Agrobacterium, Rhizobium or Bradyrhizobium strains.

PMID- 9587665
TI  - Availability of specific sugars for glycoconjugate biosynthesis: a need for
      further investigations in man.
AB  - We review the metabolism of specific sugars used for protein glycosylation,
      focusing on the fate of exogenously provided sugars. Theoretically, all
      glycoprotein sugars can derive from glucose, but previous studies show that other
      exogenous sugars can be incorporated into glycoproteins. From data obtained in
      congenital galactosemia, exogenous galactose may be important for correct
      glycosylation. Contrary to galactose, the metabolism of other sugars seems to
      depend on insulin regulation: stimulation of their endogenous production in
      diabetic subjects might participate in some diabetic complications, precluding
      the need for an exogenous supply. The metabolic fate of these sugars is different
      according to the administration route and exogenous supply may be important
      either in enteral nutrition or in some clinical situations as has been suggested
      for sialic acid in the newborn. Data in man are too sparse to reach firm
      conclusions, implying a need for further investigations. Our preliminary results
      in animals and man demonstrate that stable isotope methodology allows one to
      trace glycoprotein sugar metabolism in nutritionally relevant conditions with
      accuracy and sensitivity, using doses of specific sugars well below toxic levels.

PMID- 9587667
TI  - Glycotargeting: the preparation of glyco-amino acids and derivatives from
      unprotected reducing sugars.
AB  - Lectins are present on the surface of many cells. Many lectins actively recycle
      from membrane to endosomes and efficiently take up glycoconjugates in a sugar
      dependent manner. On this basis, glycoconjugates, specially those obtained by
      chemical means, are good candidates as carriers of drugs, oligonucleotides or
      genes. In this paper, we present a panel of methods suitable to transform
      unprotected reducing oligosaccharides into glycosynthons designed to be easily
      linked to therapeutic agents. All the glycosynthons presented here are
      glycosylamines or derivatives, mainly glyco-amino acids or glycopeptides.
      Glycosylamines are easy to obtain, but they are very labile in slightly acidic or
      neutral medium; they must be stabilized, by acylation for instance. The coupling
      efficiency of a reducing sugar with ammonia as well as an alkylamine or an
      arylamine is higher at high temperature, however, because of the Amadori
      rearrangement, special conditions have to be selected to prepare the expected
      glycosylamine derivative with a high yield. Glycosylamines are easily acylated by
      N-protected amino acids, or by halogeno acids which can then be transformed into
      amino acids. Alternatively, unprotected reducing oligosaccharides may very
      efficiently be transformed into N-glycosyl-amino acids and then protected by N
      acylation. With a glutamyl derivative having both the alpha-amino and the gamma
      carboxylic groups free, the coupling and the acylation, which is intramolecular,
      are roughly quantitative. N-oligosaccharyl-amino acid derivatives are interesting
      glycosynthons, because their sugar moiety bears the specificity towards membrane
      lectins while the amino acid part has the capacity to easily substitute a
      therapeutic agent.

PMID- 9587668
TI  - The DNA-binding protein II from Zymomonas mobilis. Complete amino acid sequence
      and interaction with DNA.
AB  - The primary structure of the DNA-binding protein II from Zymomonas mobilis has
      been determined from data provided by automated Edman degradation of the intact
      protein and of peptides derived from cleavage at aspartic acid and arginine
      residues. When compared with the homologous protein isolated from other bacteria,
      the DNA-binding protein II from Z mobilis shows many substitutions. Several non
      conservative substitutions at positions usually highly conserved in this type of
      protein probably account for the weaker DNA-binding activity of this protein
      compared to that of the E coli protein.

PMID- 9587669
TI  - Nuclear basic proteins in spermiogenesis.
AB  - In animal species, spermiogenesis, the late stage of spermatogenesis, is
      characterized by a dramatic remodelling of chromatin which involves morphological
      changes and various modifications in the nature of the nuclear basic proteins.
      According to the evolution of species, three situations can be observed: a)
      persistence of somatic histones or appearance of sperm-specific histones; b)
      direct replacement of histones by generally smaller and more basic proteins
      called protamines; and c) occurrence of a double nuclear basic protein
      transition: histones are not directly replaced by protamines but by intermediate
      basic proteins which are themselves replaced by one or several protamines.
      However, in some species, two kinds of intermediate basic proteins can be
      distinguished in spermatid nuclei: transition proteins and protamine precursors.
      Whereas transition proteins are not structurally related either to histones or to
      protamines, protamine precursors are further processed at the end of
      spermiogenesis to give rise to the mature protamine. The molecular
      characteristics of the protamines as well as number of protamine types present in
      the spermatozoon vary from species to species. In some cases, protamine-encoding
      genes, although present, are not expressed to a significant level. The diversity
      and the precise function of intermediate basic proteins remain open to
      discussion. Some of them are the precursors of protamines but the mechanism,
      sequential or not, as well as the enzyme(s) involved in the proteolytic
      processing, remain to be discovered.

PMID- 9587670
TI  - Towards structural models of molecular recognition in olfactory receptors.
AB  - The G protein coupled receptors (GPCR) are an important class of proteins that
      act as signal transducers through the cytoplasmic membrane. Understanding the
      structure and activation mechanism of these proteins is crucial for understanding
      many different aspects of cellular signalling. The olfactory receptors correspond
      to the largest family of GPCRs. Very little is known about how the structures of
      the receptors govern the specificity of interaction which enables identification
      of particular odorant molecules. In this paper, we review recent developments in
      two areas of molecular modelling: methods for modelling the configuration of
      trans-membrane helices and methods for automatic docking of ligands into receptor
      structures. We then show how a subset of these methods can be combined to
      construct a model of a rat odorant receptor interacting with lyral for which
      experimental data are available. This modelling can help us make progress towards
      elucidating the specificity of interactions between receptors and odorant
      molecules.

PMID- 9587671
TI  - The mitochondrial ADP/ATP carrier: structural, physiological and pathological
      aspects.
AB  - Under the conditions of oxidative phosphorylation, the mitochondrial ADP/ATP
      carrier catalyses the one to one exchange of cytosolic ADP against matrix ATP
      across the inner mitochondrial membrane. The ADP/ATP transport system can be
      blocked very specifically by two families of inhibitors: atractyloside (ATR) and
      carboxyatractyloside (CATR) on one hand, and bongkrekic acid (BA) and
      isobongkrekic acid (isoBA) on the other hand. It is well established that these
      inhibitors recognise two different conformations of the carrier protein, the CATR
      and BA-conformations, which exhibit different chemical, immunochemical and
      enzymatic reactivities. The reversible transition of the ADP/ATP carrier between
      the two conformations was studied by fluorometric techniques. This
      transconversion, which is only triggered by transportable nucleotides, is
      probably the same as that which occurs during the functioning of ADP/ATP
      transport system. The fluorometric approach, using the tryptophanyl residues of
      the yeast carrier as intrinsic fluorescence probes, was combined to a mutagenesis
      approach to elucidate the ADP/ATP transport mechanism at the molecular level.
      Finally, recent reports that myopathies might result from defect in ADP/ATP
      transport led us to develop a method to quantify the carrier protein in muscular
      biopsies.

PMID- 9587672
TI  - Synthetic peptides as tools to investigate the structure and pharmacology of
      potassium channel-acting short-chain scorpion toxins.
AB  - In the last decade, numerous polypeptide toxins acting on ion channels have been
      isolated and characterized from diverse scorpion venoms. These toxins are useful
      pharmacological probes to study ion-specific channel proteins because they
      interact selectively with these channels and modulate their activities. Since low
      amounts of natural toxins can be isolated from scorpion venoms, the chemical
      synthesis approach is extremely useful to produce larger quantities of toxins and
      toxin analogs. This report is a succinct overview of the possibilities offered by
      the chemical synthesis to investigate pharmacological and structural properties
      of these compounds.

PMID- 9587674
TI  - High density lipoproteins and coronary heart disease. Future prospects in gene
      therapy.
AB  - Atherosclerosis cardiovascular disease is the leading cause of death in
      industrial societies. For coronary heart disease, hypercholesterolemia and
      dyslipoproteinemia are the major risk factors. Low serum levels of cholesterol in
      the HDL fraction is the most common abnormality found in patients with confirmed
      coronary artery disease. A therapeutical strategy consists in increasing the
      serum HDL cholesterol concentration in order to improve the 'reverse cholesterol
      transport'. Studies in transgenic mice and rabbits for human apo A-I or human
      lecithin cholesterol acyl-transferase showed that overexpression of these
      proteins increases serum HDL cholesterol concentration and reduces diet induced
      atherogenesis. Furthermore, adenovirus-mediated transfer of human apo A-I and
      LCAT genes in mice also increases circulating apo A-I and LCAT. Apo A-I and LCAT
      are two potential targets for gene therapy of patients with atherosclerosis
      associated with a low HDL cholesterol level.

PMID- 9587673
TI  - Casein peptide release and passage to the blood in humans during digestion of
      milk or yogurt.
AB  - In adult humans, after milk or yogurt ingestion, many peptides derived from alpha
      s1-, beta- or kappa-caseins were detected in stomach, including the kappa
      caseinoglycopeptide, an inhibitor of platelet aggregation. Smaller peptides
      derived from casein and lactoferrin were recovered from duodenum. Two long
      peptides, the kappa-caseinoglycopeptide and the N-terminal peptide of alpha s1
      casein, were absorbed and detected in plasma. These results support the concept
      that food-born peptides could have physiological activities in man.

PMID- 9587676
TI  - The diencephalon and pretectum of the white sturgeon (Acipenser transmontanus): a
      cytoarchitectonic study.
AB  - The cytoarchitecture of the diencephalon and pretectum of the white sturgeon,
      Acipenser transmontanus, was studied utilizing cresyl violet stained serial
      paraffin sections. The identified cell groups were assigned to the preoptic area,
      hypothalamus, thalamus and posterior tubercle, epithalamus, synencephalon and
      pretectum. The outlines of the diencephalic and pretectal nuclei were projected
      graphically onto a midsagittal section of the brain, thus providing a
      reconstruction of the relative positions of the major cell groups. This
      facilitated comparisons with the diencephalic and pretectal nuclei of other ray
      finned fishes. Our cytoarchitectural analysis indicates that the diencephalon and
      pretectum of the white sturgeon is intermediate to that described for cladistians
      and neopterygians. The preoptic area in Acipenser is relatively conservative
      compared to other ray-finned fishes but lacks distinct subdivisions in the
      magnocellular periventricular preoptic nucleus and includes a unique migrated
      rostral accessory nucleus. The hypothalamic walls are rather thin, and due to the
      presence of extensive lateral and posterior recesses and the lack of migrated
      nuclei, they superficially resemble the condition seen in sharks. The dorsal and
      ventral thalamic nuclei do not exhibit much variation compared to other ray
      finned fishes, except for the presence of a small lateral posterior thalamic
      nucleus, the absence of a distinct ventrolateral thalamic nucleus, and slight
      differences in the internal organization of the ventromedial thalamic nucleus.
      The posterior tubercle in Acipenser clearly comprises more migrated cell groups
      than that of Polypterus, however, these cell groups are considerably less well
      defined than in neopterygians. As in other nonteleost actinopterygians, the
      habenular nuclei are highly asymmetrical with the right side larger than the left
      side. The cytoarchitectonic complexity of the pretectum in Acipenser is
      intermediate to that observed in Polypterus and neopterygians in that a
      magnocellular component within the superficial pretectal nucleus is clearly
      present but cannot be delineated as a distinct magnocellular superficial
      pretectal nucleus. Also, the posterior pretectal nucleus which is absent in
      Polypterus but which has been identified as a small nucleus both in Lepisosteus
      and Amia is represented in Acipenser by a small group of scattered cells.

PMID- 9587675
TI  - Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by
      macrophages. A review.
AB  - Human red blood cells (RBCs) have a life-span of 120 days in circulation, after
      which they are phagocytized by resident macrophages. Extensive studies have been
      undertaken by many investigators in order to elucidate the cellular and molecular
      mechanisms of the erythrophagocytosis. The critical questions addressed by
      physiologists, clinicians and biochemists are: 'which of the many traumatic
      blemishes that appear on the erythrocyte surface as it winds its way through the
      circulation is the primary signal for clearance of the effete RBC from the
      circulation?', or 'What is the critical signal that it, and it alone, will
      activate the resident macrophage to adhere to and engulf it?'. Numerous, and
      often conflicting, hypotheses have been proposed. Each investigator focusing on
      but one of the many modifications that afflict the cell surface of the ageing
      erythrocyte, viz changes in either or both the carbohydrate or peptidic moieties
      of glycoproteins; abolishment of the pre-existing asymmetry in the lipid bilayer
      with the exposure of phosphatidylserine residues; or alterations in spectrin, to
      mention but a few. Many of these investigators also have invoked an intermediary
      role for auto-immune antibodies that recognise the change(s) on the erythrocyte
      surface and thereby serve as opsonins as a prelude to the erythrophagocytosis.
      The objective of the present review is to evaluate the data in support of the
      various hypotheses, and to submit some of our own recent observations involving
      the use of flow cytometric procedures that: i) provide evidence that the cell
      surface sialic acid serves as a determinant of the life-span; ii) characterise
      the senescent erythrocyte population that is specifically captured and
      phagocytized by macrophages (utilising the rapid and sensitive procedure we
      developed for quantification of in vitro erythrophagocytosis); and finally iii)
      provide evidence for the existence of an alternative pathway that is independent
      of immunoglobulins.

PMID- 9587677
TI  - Somatic and dendritic mosaics formed by large ganglion cells in the retina of the
      common house gecko (Hemidactylus frenatus).
AB  - Recent studies of large ganglion cells in fishes and frogs have identified a
      shared inventory of three basic types, with characteristic forms and spatially
      independent mosaic distributions. These anamniote types and mosaics are hard to
      match to the large ganglion cell types and mosaics of mammals, implying that the
      underlying developmental programmes have diverged during evolution. Reptiles and
      mammals both belong to the amniote lineage, so the point of divergence can be
      investigated by comparing the large ganglion cells of reptiles with those of
      mammals, taking fishes and frogs as outgroups. With this aim, ganglion cells of
      the common house gecko, Hemidactylus frenatus, were labelled with horse-radish
      peroxidase by an in vitro method and studied in retinal flatmounts. Two
      prominent, regular, spatially independent mosaics were consistently present. One
      (alpha a) was characterized by somata displaced into the inner nuclear layer and
      dendrites forming planar trees in sublamina a; the other (alpha ab) comprised
      large orthotopic somata and distinctive, bistratified dendrites that formed
      discrete planar subtrees in sublaminae a and b. These subtrees were joined by up
      to 40 vertical link segments, whose distribution was found to correlate with the
      underlying photoreceptor mosaic. Some specimens also contained patches of a third
      mosaic (alpha c), characterized by large orthotopic somata and very large flat
      trees in sublamina c, but the labelling of this type was inconsistent. These
      reptilian mosaics share several distinctive characters with anamniote alpha-cell
      mosaics but differ markedly from the ganglion cell mosaics of any known mammal.
      The most parsimonious conclusion is that those mosaic features that are shared by
      the ganglion cells of all nonmammals are homologous and primitive
      (symplesiomorphic), while those that are shared by all therian mammals are
      homologous and derived (synapomorphic). This is consistent with other differences
      between mammalian and nonmammalian eyes. Mosaic formation itself, however, seems
      to be a universal characteristic of large ganglion cells.

PMID- 9587678
TI  - Calbindin immunoreactivity in Purkinje cells of the bullfrog cerebellum during
      thyroxine-induced metamorphosis.
AB  - Calbindin-immunoreactive Purkinje cells were identified in the cerebella of frog
      tadpoles that had been treated with thyroxine to accelerate metamorphosis. The
      dorsal part of the cerebellar plate contained the full complement of Purkinje
      cells which were all CaBP-immunoreactive, while in the ventral part of the
      cerebellum Purkinje cells acquired CaBP-immunoreactivity only after several days
      of thyroxine treatment. The ventral group of Purkinje cells was separated from
      the dorsal group by a distinct gap, which is the site of a shallow sulcus in
      adult frogs. Additionally, following thyroxine treatment, the numbers of CaBP
      immunoreactive Purkinje cells in the ventral group were only half the numbers
      seen in frogs that metamorphosed spontaneously. We suggest that the variation in
      the CaBP-immunoreactivity of the dorsal and ventral groups of Purkinje cells,
      along with the gap in the Purkinje cell layer between the two groups, may be
      indicative of two distinct populations of Purkinje cells, with distinct patterns
      of generation, maturation, and perhaps, origin and connectivity, in the
      cerebellum of frogs.

PMID- 9587679
TI  - Interferon therapy of hematologic malignancies.

PMID- 9587680
TI  - Interferon use in solid tumors.

PMID- 9587681
TI  - Cellular vaccine therapies for cancer.

PMID- 9587682
TI  - Anti-idiotype antibody vaccine therapies of cancer.

PMID- 9587683
TI  - Endocrine therapy of prostate cancer.
AB  - Endocrine therapy is effective treatment for patients with metastatic prostate
      cancer. Most patients will benefit from androgen withdrawal in terms of
      symptomatic relief and delay in progression of diseases. It does not, however,
      cure patients with metastatic prostate cancer. This finding emphasizes the need
      for the development of effective nonendocrine therapies.

PMID- 9587684
TI  - Endocrine therapy of endometrial cancer.

PMID- 9587685
TI  - Phytochemicals for the prevention of breast and endometrial cancer.
AB  - Although there is evidence that phytochemicals decrease the incidence of breast
      and endometrial cancer, many observations are only phenomenologic, and much work
      needs to be done to explore basic mechanisms and the strategic exploitation of
      their interactions. The multiplicity of phytochemical actions at different sites
      in the process of tumorigenesis may eventually lead to the development of a
      multiagent strategy designed to maximize the complementary effects of different
      agents. A number of effects with possible relevance to cancer chemoprevention
      have been excluded from this review, including effects of phytochemicals on the
      immune response; the question of dietary restriction, which has a profound effect
      on tumorigenesis; the relatively low methionine levels in some phytochemicals
      such as soy, which may limit the synthesis of polyamines necessary for tumor
      growth [151]; and the fact that diets higher in plant products are usually lower
      in fat and result in leaner individuals with less potential for the synthesis of
      estradiol in adipose tissue. Also, many studies dealing solely with in vitro
      mutagenesis were excluded.

PMID- 9587686
TI  - Hormonal strategies for the prevention of breast cancer.

PMID- 9587687
TI  - Ovarian ablation as adjuvant therapy for early-stage breast cancer.

PMID- 9587688
TI  - The duration of adjuvant tamoxifen therapy.

PMID- 9587689
TI  - Tamoxifen and the endometrium.

PMID- 9587690
TI  - Hormone replacement therapy and nonhormonal control of menopausal symptoms in
      breast cancer survivors.

PMID- 9587691
TI  - Endocrine therapy in metastatic breast cancer.
AB  - Endocrine therapy represents a mainstay of effective, minimally toxic, palliative
      treatment for metastatic breast cancer. Research focusing on the mechanism of
      action of endocrine agents will provide new insights leading to new hormonal
      approaches in breast cancer treatment. Development of new agents, especially the
      'pure' antiestrogens, is of great interest. Combining endocrine therapy with
      biologic agents, especially antiproliferative compounds, may lead to more
      effective treatment in the adjuvant as well as the advanced setting. Tables 4 and
      5 summarize response rates to the different groups of endocrine agents used in
      metastatic breast cancer and doses of commonly used agents, respectively. At
      present, tamoxifen is the drug of choice as first-line endocrine therapy for
      metastatic breast cancer with no or minimal symptoms in premenopausal or
      postmenopausal women. Second-line therapy usually consists of megace. Aromatase
      inhibitors may be used as second- or third-line therapy in postmenopausal women.
      In premenopausal women, LHRH analogues are a reasonable choice. The other
      hormonal agents may be beneficial as salvage therapy. More effective endocrine
      approaches are under development.

PMID- 9587692
TI  - The regulation of estrogen receptor expression and function in human breast
      cancer.

PMID- 9587693
TI  - The first twelve cases of computer assisted periacetabular osteotomy.
AB  - Image guided freehand navigation of surgical instruments has been applied to the
      Bernese periacetabular osteotomy, a complex surgical technique for the treatment
      of dysplastic hips. This navigation system has been introduced into the operating
      room and has so far been used for 12 patients. Image data from computed
      tomography (CT) scans are presented in various ways to support the preoperative
      plan and to provide optimized control of surgical action. Special attention has
      been paid to the implementation of a sophisticated surgeon-machine interface.
      This paper describes the features of this novel surgical navigation system and
      its introduction into the clinical environment.

PMID- 9587694
TI  - Interactive image-guided resection of cerebral cavernous malformations.
AB  - Between July 1992, and February 1997, 15 patients with cavernous malformations
      underwent interactive image-guided resection of their lesions. There were eight
      women and seven men in the group, ranging in age from 6 years to 62 years (mean
      34 years). Clinical presentations included seizures (n = 7), headache (n = 4),
      and hemorrhage (n = 4). Prior conventional subtotal resection had been performed
      in one patient, and a history of prior hemorrhage was found for two patients.
      Diagnosis was made using magnetic resonance imaging and digital substraction
      angiography. Locations of the lesions were temporal (n = 9), frontal (n = 3),
      thalamus (n = 1), basal ganglia (n = 1), and pons (n = 1). Size ranged from 9 to
      20 mm (mean 12 mm). For those lesions located near or within eloquent areas (n =
      7), an awake craniotomy with functional cortical and subcortical mapping was
      performed. An infrared system was used intraoperatively to confirm the location
      and the extent of the resection of these lesions in real time. In 1996 we started
      using a robotic microscope to aid in localization and resection. Clinical follow
      up ranged from 2 to 54 months (mean 27 months). In all 15 patients, complete
      surgical resection was achieved as demonstrated by postoperative magnetic
      resonance imaging studies. Two patients had postoperative transient neurological
      deficits (13.3%) that cleared over a 6-month period. One of them had a lesion in
      the pons, with multiple cranial nerve deficits postoperatively that gradually
      improved. There was no associated mortality. Histological diagnosis was
      consistent with cavernous angioma in all cases. Clinical follow-up revealed that
      13 patients experienced complete recovery from preoperative symptoms and two
      patients with seizures showed marked improvement. We conclude that interactive
      image-guided surgery for deep-seated cavernous malformations represents a very
      accurate and safe approach.

PMID- 9587696
TI  - Experimental cryosurgery of the liver under magnetic resonance guidance.
AB  - The feasibility and the advantages of magnetic resonance (MR)-guided interstitial
      cryosurgery of the liver in an 0.5 Tesla open MR system have been evaluated.
      Cryosurgery was performed using an Erbocryo PS system with a nonmagnetic
      cryoprobe of 6 mm diameter. The probe was inserted into the liver parenchyma
      under real-time MR control. Using continuous MR imaging two freezing cycles of 12
      min each were applied. After conventional and dynamic gadolinium-enhanced MR
      imaging, the animals were sacrificed after 30 min, 3 hr, 24 hr, 7 days, and 21
      days. Each lesion was analyzed using light microscopy. A total of seven
      cryolesions were made in five animals without any complications from cryosurgery.
      During real-time imaging, cryolesions appeared as a hemispherical growing signal
      loss with a mean volume of 16.4 cm3. Macroscopic volumes of the lesions showed a
      good correlation with dynamic enhanced MR images during follow-up, whereas real
      time images usually showed an underestimation of the lesion volumes. Cryosurgery
      of the liver in an open-configuration MR system is a feasible and safe method. MR
      imaging allows the guidance and the follow-up of cryolesions of the liver with
      good accuracy.

PMID- 9587695
TI  - Simulated surgery on computed tomography and magnetic resonance images: an aid
      for intraoperative radiotherapy.
AB  - Intraoperative radiotherapy (IORT) is a relatively new technique in which
      irradiation with electrons is performed during an open surgery procedure. This
      approach poses significant problems in obtaining accurate dosimetry, since
      neither the pre- nor the postoperative patient images actually matches the
      irradiation field. Our objective was to implement a software tool able to provide
      an estimate of the dose distribution, overcoming the problem of the geometrical
      mismatch between the images and the surgical field during the irradiation. The
      program was developed in the C programming language, on a noncommercial version
      of a Philips EasyVision workstation. The application allows to create a new data
      set by manipulating the preoperative computed tomography and magnetic resonance
      images in order to simulate the final geometry of the surgical area during the
      IORT procedure. The exact dose distribution can then be calculated by
      transferring these new images to a standard radiotherapy planning system. Also an
      approximate dose distribution can be quickly displayed by superimposing isodose
      curves obtained from a water phantom. The proposed approach introduces a helpful
      tool for dosimetry and planning in IORT protocols, improving their accuracy and
      safety and allowing for more objective quality control and patient follow-up.

PMID- 9587697
TI  - Effect of image artifacts, organ motion, and poor segmentation on the reliability
      and accuracy of three-dimensional chamfer matching.
AB  - Our objective was to investigate the influence of various image artifacts on
      three-dimensional chamfer matching. A number of artificial and natural artifacts
      (for instance, as a model for CT-MR matching) were introduced or suppressed in
      pairs of pelvic CT scans, and a perturbation study was used to determine
      reliability and accuracy in a well known ground truth situation. In general,
      chamfer matching is extremely robust against missing data, low resolution, and
      poor segmentation of the images. In the presence of artifacts, minimization of
      the average distance outperformed minimization of the root-mean-square distance.
      Outliers in the scan from which the point list is obtained must be avoided. For
      example, rotation of the femurs reduces CT-CT registration accuracy by 1-2 mm.
      The robustness of chamfer matching is confirmed by a limited perturbation study
      of CT-MR registration for the pelvic region. In conclusion, chamfer matching is
      extremely accurate and reliable if outliers are avoided in the scan from which
      the point list is derived, and the average distance is used as a cost function.

PMID- 9587698
TI  - Computer assisted pericardial puncture: work in progress.
AB  - Until now, computer assisted surgery has focused primarily on surgical procedures
      involving rigid anatomical structures. Because soft tissues can be highly mobile
      and deformable, they may require specific imaging devices, suitable modeling
      tools, and guiding systems. Percutaneous pericardial puncture is a good clinical
      target for computer assisted surgery; this procedure is often performed without
      direct visualization and is dangerous even though echographic control is used.
      Computer assistance can greatly improve this technique and will allow accurate
      puncture of preplanned targets. This paper describes a new approach for computer
      assisted pericardial punctures (CASPER) and describes a first feasibility
      analysis of CASPER demonstrated with anesthetized animals. The approach is based
      on the use of echographic data localized in space, from which an optimal strategy
      is defined. Because of the specificity of the pericardial effusion, a stable
      target can be selected despite the heart motions. A passive guiding system is
      used. We have demonstrated the feasibility of the approach.

PMID- 9587699
TI  - The EGF receptor system in head and neck carcinomas and normal tissues.
      Immunohistochemical and quantitative studies.
AB  - The EGF receptor (EGF receptor) and two of the ligands, transforming growth
      factor alpha (TGF-alpha) and epidermal growth factor (EGF), exert mitogenic
      activities in epithelial cells. Hence, the overall aim of this work was
      delineation of the EGF receptor system in head and neck carcinomas, which in the
      majority of cases are epithelial derived tumours. Chapter 1 is a general
      introduction to head and neck carcinomas and the relevance of the EGF receptor
      system in this context. Chapter 2 focuses on the immunohistochemical distribution
      of TGF-alpha in normal human tissues, while previous studies dealing with the
      growth factor in head and neck carcinomas revealed other localizations in normal
      cells. TGF-alpha was detected with monoclonal as well as polyclonal antibodies.
      The results showed that the growth factor is widely distributed in normal human
      tissues and thus not limited to malignant cells. Chapter 3 describes the
      immunohistochemical localization of the EGF receptor in 55 patients with squamous
      cell carcinoma in the head and neck region. The study included adjacent normal
      mucosa and in 12 cases additional dysplastic areas were present. The EGF receptor
      was found in the basal cell layer in normal oral and laryngeal mucosa. In
      sections from patients who had received preoperative irradiation the receptor was
      in addition seen on the spinous cells. In dysplastic epithelial all cells stained
      for the EGF receptor. The majority of the head and neck carcinomas expressed the
      EGF receptor. In poorly differentiated tumours almost all cells were positive for
      the receptor. Sections from moderately and well differentiated tumours
      demonstrated a reduction in the extent of stained areas, paralleling the
      situation observed in the differentiated upper layers of normal oral and
      laryngeal mucosa. Furthermore, this chapter describes the EGF receptor
      quantitatively in 60 patients with head and neck carcinoma. This study was
      performed in order to evaluate if overexpression of the EGF receptor was a common
      motif for head and neck carcinomas. The level in tumour biopsies was compared
      with the level in the patients' corresponding normal mucosa. An enzyme-linked
      immunosorbent assay detecting protein epitopes of the receptor was employed.
      Overexpression of the receptor was found in the majority of cases. The
      overexpression was further correlated to clinicopathological parameters. However,
      no significant correlations were found although the mean values increased with
      increased tumour size and advanced clinical stage. The use of quantitative assays
      are further discussed and limitations are emphasized with respect to
      heterogeneity at the EGF receptor level and the varying stromal components in
      malignant tissues. Despite these problems the relevance of the EGF receptor a
      therapeutic situation is illustrated with e.g. EGF receptor antibodies and
      tyrosine-kinase inhibitors. Chapter 4 focuses on the immunohistochemical
      expression of EGF and TGF-alpha in carcinomas from same 55 patients. This study
      included adjacent normal mucosa in which the growth factors were expressed above
      the basal cell layer. The majority of the tumours expressed both growth factors
      and none of the sections were negative for both EGF and TGF-alpha. In biopsies
      from moderately and well differentiated tumours the growth factors were
      demonstrated in the more differentiated cells. However, in poorly differentiated
      tumours the cells were positive for EGF and TGF-alpha. Chapter 5 describes
      immunohistochemical and quantitative changes of salivary EGF, amylase and
      haptocorrin following radiotherapy for oral cancer. This study was initiated
      because irradiated oral and laryngeal mucosa have demonstrated staining for the
      receptor in the basal cell layer as well as in the spinous cells, indicating an
      upregulation of the receptor in response to lack of EGF. In normal biopsies from
      the glandula submandibularis and glandula parotis, EGF and amylase were
      demonstrated in the serous acini, whereas haptoc

PMID- 9587700
TI  - Colon as a digestive organ. The importance of colonic support for energy
      absorption as small bowel failure proceeds.

PMID- 9587701
TI  - Interleukin-1 beta induced transient diabetes mellitus in rats. A model of the
      initial events in the pathogenesis of insulin-dependent diabetes mellitus?
AB  - When aiming at preventing IDDM in man, knowledge of the molecular mechanisms
      leading to beta cell destruction may facilitate identification of new possible
      intervention modalities. A model of IDDM pathogenesis in man suggests that
      cytokines, and IL-1 in particular, are of major importance in the initial events
      (Nerup et al 1994) (Fig. 1). In vitro rat experiments demonstrated that rhIL-1
      beta inhibits beta cell function and induces beta cell death both in isolated
      islets of Langerhans and in the isolated perfused pancreatic gland. With the long
      term goal of identifying new modalities capable of preventing IDDM in man, the
      aim af this review was to investigate the effects of rhIL-1 beta on beta-cell
      function and viability in normal rats. This review discussed 1) the
      pharmacokinetics of IL-1 beta in rats as the basis for choice of route of
      administration and dose of rhIL-1 beta, 2) the effects and molecular mechanisms
      of IL-1 beta on temperature and food intake used as control parameters for
      successful injection of rhIL-1 beta in rats, 3) the effects of one or more
      injection of IL-1 beta on rat beta cell function, 4) the molecular mechanisms
      leading to IL-1 beta induced beta cell inhibition in vivo, and some possible
      intervention modalities based on the molecular mechanisms, 5) the effects of IL-1
      beta on spontaneous diabetes mellitus in DP BB rats, and 6) the effects and
      molecular mechanisms of IL-1 beta induced inhibition of thyroid epithelial cell
      function and aggravated thyroiditis in DP BB rats, compared to the effects of IL
      1 beta on rat beta cell function. Finally, this review discussed the effects of
      IL-1 beta on human beta cells in vitro, and the clinical relevance of these
      experiments, with special reference to a clinical trial with the aim of
      preventing IDDM in man. The pharmacokinetic studies suggested that IL-1 beta is
      distributed according to a two-compartment model with a first-order elimination.
      Interleukin-1 beta reached all the investigated organs in the rats, was
      accumulated in kidneys and was excreted in the urine. The data suggested that IL
      1 beta also accumulated in the islets of Langerhans. After injection of 4.0
      micrograms/kg pathophysiologically relevant concentrations of rhIL-1 beta were
      reached and intact rhIL-1 beta persisted for up to 5 hrs in plasma. Peripheral
      injections of IL-1 beta dose-dependently induced fever and anorexia in rats,
      probably via induction of PGE2 in the brain or in peripheral tissues thereafter
      passing the blood-brain barrier. Nitric oxide produced by cNOS seems to be a
      molecular mediator of IL-1 beta induced fever but not of anorexia. Fever and
      anorexia are well described effects of IL-1 beta in rats, and are as such usefull
      control parameters of the absorption and biological activity of IL-1 beta after
      peripheral injection. Injections of rhIL-1 beta to normal, non-diabetes prone
      rats induced initial beta cell stimulation followed by inhibition, in accordance
      with in vitro data. Furthermore, induction of peripheral insulin resistance
      coincided with beta cell inhibition after one daily injection for 5 days, leading
      to a transient diabetes mellitus-like state, characterized by hyperglycemia and
      hypoinsulinemia. At this time point, electron-microscopy did not demonstrate beta
      cell destruction. However, IL-1 beta induced intercellularly edema and
      microvillous processes on the beta cells, which might be early evidence of
      apoptosis. The diabetes mellitus-like state was not aggravated if the daily
      injections were continued beyond 5 days. Daily injections of rhIL-1 beta for 2 to
      4 weeks induced formation of blocking IL-1 beta-antibodies in normal rats. Hence,
      injections exceeding 2 weeks should only be performed using species homologous IL
      1 beta. The molecular mechanism of IL-1 beta induced beta cell inhibition in rats
      in vivo as in vitro, are likely to involve binding of IL-1 beta to the IL-1RtI,
      since the IL-1RtII is considered to be a decoy receptor. (ABSTRACT TRUNCATED)

PMID- 9587702
TI  - Progressive chronic nephropathy. With special emphasis on the influence of
      angiotensin converting enzyme inhibition.

PMID- 9587703
TI  - Bronchoscintigraphy and pulmonary clearance of 99mTc-albumin colloid in the study
      of mucociliary clearance.

PMID- 9587704
TI  - Polypharmacy and the risk of drug-drug interactions among Danish elderly. A
      prescription database study.
AB  - OBJECTIVE: To analyze the use of all subsidized prescription drugs with special
      attention to the elderly (> or = 70 years of age), including their use of drug
      combination generally accepted as carrying a risk of severe interactions. DESIGN:
      Descriptive prevalence study. SETTING: Odense Pharmacoepidemiological Database,
      Denmark. The fourth quarter of 1994. SUBJECTS: All inhabitants in the county of
      Funen, Denmark. MAIN OUTCOME MEASURES: Prevalence of drug use for persons < 70
      and > or = 70 years of age including number of drugs used and of drug
      combinations. Occurrence of 45 drug combinations generally accepted as carrying a
      risk of severe interactions. RESULTS: Among persons less than 70 years, 67.9%
      used none, 16.5% used one drug and 15.6% used two or more prescription drugs. The
      corresponding prevalences for the elderly were 35.7%, 15.9% and 48.4%. The 26,337
      elderly patients with at least two drugs used 21,293 different combinations. Of
      the elderly patients who had purchased > or = two drugs, 4.4% had combinations of
      drugs carrying a risk of severe interactions. CONCLUSIONS: Most elderly use drugs
      and usually several drugs concomitantly. The elderly form a heterogeneous group
      of drug users. Drug combinations carrying a risk of severe interactions are
      relatively frequent.

PMID- 9587705
TI  - Folate and neural tube defects. Recommendations from a Danish working group.
AB  - A working group was established to evaluate the need for an increased folate
      intake in Danish women to decrease the risk of neural tube defects (NTDs). NTD
      are birth defects which include anencephaly, encephalocele and spina bifida. In
      Denmark the incidence is about 1.4 per 1,000 pregnancies. Folate is a B-vitamin
      found in most food groups. In case-control studies and randomised studies, a
      protective effect of folic acid supplements on NTDs has been found. The studies
      show that a periconceptional folic acid supplement of 360 micrograms to 4 mg
      daily decreases the recurrence rate of NTDs. Likewise, in the few studies which
      calculate folate intake from the diet, a lower risk of NTD with higher intake of
      folate from the diet has been found. The folate intake can be increased by the
      diet, by folic acid supplements or by fortification of food with folic acid. It
      is concluded that the incidence of NTDs in Denmark will decrease if the folate
      intake in fertile women increases. All women planning pregnancy should receive
      dietary counselling. Women who do not eat according to the Nordic Nutrition
      Recommendations, and women with an increased risk due to diseases are recommended
      a supplement of 400 micrograms folic acid daily from a multivitamin/folic acid
      tablet. Women who have had a child with NTD and women who themselves have NTDs
      are recommended a supplement of 5 mg folic acid daily. Dietary changes and
      supplements should be initiated when pregnancy is planned.

PMID- 9587706
TI  - Trends in health expectancy in Denmark, 1987-1994.
AB  - OBJECTIVE: To estimate health expectancy in Denmark and evaluate changes during
      the period 1987-1994. DESIGN: Life-table figures from vital statistics combined
      with prevalence data of population health status derived from the Danish Health
      Interview Surveys carried out in 1987, 1991, and 1994. SETTING AND SUBJECTS: The
      Danish population aged 16 years and over. MAIN OUTCOME MEASURES: Health
      expectancy calculated by Sullivan's method combining mortality and morbidity into
      a single indicator. This indicator estimates the average lifetime in good health.
      Relating health expectancy to life expectancy gives a measure of the proportion
      of lifetime in good health. RESULTS: Although life expectancy has remained stable
      since the beginning of the 1980s health expectancy has changed slightly over the
      period 1987-1994, with a positive trend for men but a negative one for women.
      CONCLUSION: The results underline the concern about the health of Danish women
      expressed in recent years. Health expectancy could be increased by successful
      prevention of musculo-skeletal diseases, which account for the highest proportion
      of lifetime with long-standing illness.

PMID- 9587707
TI  - The Danish Fertility Database.
AB  - BACKGROUND: The Fertility Database (FTDB) in Statistics Denmark is solely based
      on data from other registers, which comprise data on a different number of birth
      cohorts and different time spans. The FTDB was established during 1989-1992 in
      order to provide a better tool for socio-demographic research on the developments
      in fertility. The variables included also make the register a valuable tool in
      medical research regarding reproductive outcome and characterization of parents.
      RESULTS: Based on the Register of Population Statistics, the FTDB comprises at
      present annual information on any woman and man in the fertile age in Denmark for
      the period 1980-1993, approximately 1.2 and 1.4 million persons, respectively.
      Their children are identified through various registers and for all children born
      1973-1993 specific information on the birth was available from the Medical
      Register of Vital Statistics. The adult populations are described annually as
      regards education, occupation, income, social benefit and housing conditions.
      CONCLUSION: The FTDB has been used in a number of research projects; in some
      cases data from the FTDB have been linked with data from other registers. The
      FTDB is a valuable tool in demographic as well as medical research.

PMID- 9587708
TI  - A comparative analysis of the murine thymic microenvironment in normal,
      autoimmune, and immunodeficiency states.
AB  - It is widely accepted that the thymic microenvironment regulates normal
      thymopoiesis through a highly coordinated and complex series of cellular and
      cytokine interactions. A direct corollary of this is that abnormalities within
      the microenvironment could be of etiologic significance in T-cell-based diseases.
      Our laboratory has developed a large panel of monoclonal antibodies (mAbs) that
      react specifically with epithelial or nonepithelial markers in the thymus. We
      have taken advantage of these reagents to characterize the thymic
      microenvironment of several genetic strains of mice, including BALB/cJ, C57BL/6J,
      NZB/BlnJ, SM/J, NOD/Ltz, NOD/Ltz-scid/sz, C57BL/6J-Hcphme/Hcphme, and ALY/NscJcl
      aly/aly mice, and littermate control animals. We report herein that control mice,
      including strains of several backgrounds, have a very consistent phenotypic
      profile with this panel of monoclonal antibodies, including reactivity with
      thymic epithelial cells in the cortex, the medulla and the corticomedullary
      junction, and the extracellular matrix. In contrast, the disease-prone strains
      studied have unique, abnormal staining of thymic cortex and medulla at both the
      structural and cellular levels. These phenotypic data suggest that abnormalities
      in interactions between developing thymocytes and stromal cells characterize
      disease-prone mice.

PMID- 9587709
TI  - Requirements for differentiation of an immature CD4+8+ T-cell line.
AB  - The CD3 epsilon and zeta chains of the TCR have been shown to possess independent
      signaling capabilities. Studies with chimeric molecules containing the
      cytoplasmic domains of either zeta or epsilon have suggested that these two
      structurally distinct members of the TCR-CD3 complex are able to function
      autonomously and have redundant features in the context of TCR-signal
      transduction in mature T cells. Expression of a chimeric human IL-2-receptor-zeta
      chain molecule in the CD4+8+ T-cell line, DPK, has enabled us to directly analyze
      responses initiated by the zeta-chain-signaling module alone within the context
      of immature T-cell differentiation. In this paper, we show that antibody
      crosslinking of the chimeric zeta chain delivers only a limited activation signal
      as measured by Ca[2+] flux, induction of low-level CD5 expression, and minimal
      differentiation as assessed by loss of cell-surface CD8 expression. TCR-induced
      activation through antibody crosslinking of the endogenous CD3 epsilon receptor
      in the absence of costimulation was also relatively inefficient in initiating
      activation and differentiation. However, co-crosslinking of the CD4 coreceptor
      with CD3 resulted in a synergistic response, where as there was little effect of
      co-crosslinking of CD4 and the zeta-chain chimera. Striking differences were also
      observed in the substrate pattern of tyrosine phosphorylation, as well as
      lymphokine secretion following triggering through the intact TCR versus the zeta
      chain alone. These results indicate that although the zeta-chain may possess some
      signaling capacities similar to that of the intact TCR, it appears to have
      limited function as an autonomous subunit in initiating CD4+8+ T-cell
      differentiation.

PMID- 9587710
TI  - A protein binding specifically to the IgG2b switch region.
AB  - The Abelson-virus-transformed mouse pre-B-cell line 18-81 switches almost
      exclusively from mu to gamma 2b. From nuclear extracts of this cell line, we have
      isolated a factor that specifically binds to S gamma 2b. After an eight-step
      purification scheme, in which different types of DNA-affinity chromatography were
      used as key elements, we obtained a preparation with two narrowly spaced bands at
      approximately 69 kD on a silver-stained SDS gel. Binding specificity of main-peak
      fractions of affinity-purified proteins was analyzed by gel shift assays, in
      which S gamma 2b, but not S mu, competes. The results are consistent with this
      factor being part of the switch recombinase.

PMID- 9587711
TI  - Both IFN-gamma and IL-4 induce MHC class II expression at the surface of mouse
      pro-B cells.
AB  - Pro-B cells are early B-cell progenitors that retain macrophage potential. We
      have studied MHC class II molecules and invariant chain inducibility on four
      class II negative mouse pro-B-cell clones. We analyzed the effects of IL-4 and
      IFN-gamma, which represent the major inducers of class II in the B-lymphoid and
      monocytic/macrophage lineages, respectively. After 48 h of treatment with either
      cytokine, three pro-B-cell clones (C2.13, A1.5, and F2.2) expressed intracellular
      invariant chain and cell-surface class II molecules. One clone (D2.1) remained
      negative. As already reported, more differentiated 70Z/3 pre-B cells were
      inducible by IL-4 only. These data suggest that the induction of class II and
      invariant-chain genes are subject to regulation throughout B-cell
      differentiation.

PMID- 9587712
TI  - The neonatal development of intraepithelial and lamina propria lymphocytes in the
      murine small intestine.
AB  - During early neonatal life, important changes occur in the gut. The intestine is
      challenged by both milk and a microbial flora. Later on, at weaning, the diet of
      mice changes from milk to pelleted food leading to changes in microbial contents.
      This period seems essential for a complete development of the mucosal immune
      system. We investigated the development of both intraepithelial (IEL) and lamina
      propria lymphocytes (LPL), from day 5, and every 5 days, up to day 30 after
      birth. IEL and LPL were isolated from the small intestine and the phenotype was
      assessed by FACS analyses, using antibodies for detection of T-cell markers CD3,
      TCR alpha beta, TCR gamma delta, CD4, CD8 alpha, CD8 beta, CD5, CD18, CD54, and
      CD49d. Our data show a clear increase in the number of LPL just before weaning,
      while the number of IEL increased after day 15. A more mature pattern of membrane
      antigen expression of both IEL and LPL was observed at weaning. The adhesion
      molecules CD18, CD54, and CD49d, essential for cellular communication of
      lymphocytes, showed an expression peak at weaning. In conclusion, the mouse
      mucosal immune system develops during the first 3 weeks of neonatal life leading
      to the formation of a more mature immune system at weaning.

PMID- 9587713
TI  - Inspection of the 3' UTR genomic region for RAG1 and RAG2 in rainbow trout
      (Oncorhynchus mykiss) reveals potential regulatory motifs.

PMID- 9587714
TI  - Involvement of thyroid hormones in the expression of MHC class I antigens during
      ontogeny in Xenopus.
AB  - The major histocompatibility complex (MHC) is a cluster of genes encoding
      products central to all major functions of the vertebrate immune system. Evidence
      for an MHC can be found in all vertebrate groups that have been examined except
      the jawless fishes. Expression of MHC class I and class II antigens early in
      ontogeny is critically important for development of T lymphocytes capable of
      discriminating self from nonself. Because of this essential role in T-cell
      development, the ontogeny of MHC expression in the South African clawed frog,
      Xenopus laevis, was studied. Previous studies of MHC class I expression in
      Xenopus laevis suggested that class I antigens are virtually absent from tadpole
      tissues until climax of metamorphosis. We therefore examined the possible role of
      thyroid hormones (TH) in the induction of class I. By flow cytometry, a small
      amount of class I expression was detectable on splenocytes and erythrocytes in
      untreated frogs at prometamorphic stages 55-58, and the amount increased
      significantly at the conclusion of metamorphic climax. Thus, metamorphosis is
      associated with increased intensity of class I expression. Neither inhibition nor
      acceleration of metamorphosis altered the timing of onset of class I expression.
      However, inhibition of metamorphosis prevented the increase in class I expression
      characteristic of adult cell populations. Because expression was not accelerated
      in TH-treated frogs or delayed in metamorphosis-inhibited frogs, it is unlikely
      that TH are the direct developmental cues that induce expression, although they
      seem to be required for the upregulation of class I expression occurring at
      metamorphosis. Differences in the pattern of expression in different sub
      populations of cells suggest a complex pattern of regulation of expression of
      class I antigens during ontogeny.

PMID- 9587716
TI  - Eltanolone: 50 years on and still looking for steroid hypnotic agents!

PMID- 9587715
TI  - Involvement of glucocorticoids in the reorganization of the amphibian immune
      system at metamorphosis.
AB  - In recent years, integrative animal biologists and behavioral scientists have
      begun to understand the complex interactions between the immune system and the
      neuroendocrine system. Amphibian metamorphosis offers a unique opportunity to
      study dramatic hormone-driven changes in the immune system in a compressed time
      frame. In the South African clawed frog, Xenopus laevis, the larval pattern of
      immunity is distinct from that of the adult, and metamorphosis marks the
      transition from one pattern to the other. Climax of metamorphosis is
      characterized by significant elevations in thyroid hormones, glucocorticoid
      hormones, and the pituitary hormones, prolactin and growth hormone. Previously,
      we and others have shown that elevated levels of unbound glucocorticoid hormones
      found at climax of metamorphosis are associated with a natural decline in
      lymphocyte numbers, lymphocyte viability, and mitogen-induced proliferation. Here
      we present evidence that the mechanism for loss of lymphocytes at metamorphosis
      is glucocorticoid-induced apoptosis. Inhibition of lymphocyte function and loss
      of lymphocytes in the thymus and spleen are reversible by in vitro or in vivo
      treatment with the glucocorticoid receptor antagonist, RU486, whereas the
      mineralocorticoid receptor antagonist, RU26752, is poorly effective. These
      observations support the hypothesis that loss of larval lymphocytes and changes
      in lymphocyte function are due to elevated concentrations of glucocorticoids that
      remove unnecessary lymphocytes to allow for development of immunological
      tolerance to the new adult-specific antigens that appear as a result of
      metamorphosis.

PMID- 9587717
TI  - The pharmacology of ornipressin (POR-8): a local vasoconstrictor used in surgery.

PMID- 9587718
TI  - Opioids in obstetrics: which route of administration with which opioid do we
      choose to establish effective analgesia?

PMID- 9587719
TI  - Effect of balanced analgesia with buprenorphine on pain response and general
      anaesthesia requirement during lithotripsy procedures.
AB  - The effectiveness of a balanced analgesia with buprenorphine ketoprofen
      propacetamol for pain control during extracorporeal shock wave lithotripsy (ESWL)
      was evaluated in order to reduce the requirements for general anaesthesia. Two
      hundred and ninety-one consecutive patients were included in a randomized,
      placebo-controlled, double-blind study. Patients in each group received midazolam
      5 mg pre-operatively as premedication. The subjects then received either placebo
      (group 1), buprenorphine 0.3 mg (group 2) or the combination buprenorphine 0.3 mg
      plus ketoprofen 100 mg and propacetamol 2 g (group 3) intravenously (i.v.) at a
      constant rate. The treatment was started 45 min prior to ESWL. Pain was assessed
      using a three-point verbal scale: (0)no pain; (1) moderate pain; and (2) intense
      pain needing general anaesthesia. The patients assessed their pain intensity on a
      0-100 mm visual analogue scale. Only 69% of group 1 patients received ESWL with
      midazolam premedication. Buprenorphine provided good analgesia in 87% of group 2
      patients, while the combination buprenorphine-ketoprofen-propacetamol was
      effective in 99% of group 3 patients (P < 0.05). The incidence of nausea and
      vomiting was similar in the buprenorphine groups. No respiratory depression was
      reported. In conclusion, the buprenorphine-ketoprofen-propacetamol combination
      provided effective analgesia, allowing ESWL to be performed without the need for
      general anaesthesia.

PMID- 9587720
TI  - Reducing the incidence of sore throat with the laryngeal mask airway.
AB  - The incidence of sore throat after the use of the laryngeal mask was assessed
      with a randomized trial in 839 patients. Sore throat occurred more often in
      women, older patients or after multiple insertion attempts. It was found that the
      frequency in women, but not in men, was lowered from 11.9% to 3.9% (P = 0.012) by
      reducing intracuff pressure to the minimum required for an effective seal.

PMID- 9587721
TI  - Antioxidant activity of propofol in blood from anaesthetized patients.
AB  - The antioxidant capacity of plasma taken from 10 patients before and during
      propofol anaesthesia was measured. Mean total plasma antioxidant activity fell
      from 1.73 to 1.64 mM L-1 trolox equivalents (P = 0.047). This was caused by
      haemodilution since mean haemoglobin concentration fell from 13.0 to 12.5 g dL-1
      (P = 0.016). The time to 50% haemolysis (H50) of 10% red blood cell suspensions
      induced by 2,2'azo-bis(2-amidinopropane) dihydrochloride (ABAP) was measured in
      blood from six patients. There was no change when red cells alone were studied,
      but when the patients' plasma was added to red cell suspensions (producing 10%
      plasma and 10% red cell suspensions), mean H50 increased from 291 to 308 min (P =
      0.049). Despite there being no overall increase in plasma antioxidant activity,
      the lipid soluble component of blood antioxidant activity appears to be increased
      by propofol.

PMID- 9587722
TI  - Comparison of caudal bupivacaine, bupivacaine-morphine and bupivacaine-midazolam
      mixtures for post-operative analgesia in children.
AB  - Sixty children undergoing inguinal or urogenital surgery were allocated randomly
      to three groups to receive a caudal injection of either 0.125% bupivacaine 0.75
      mL kg-1 with 0.5% midazolam 50 micrograms kg-1 (n = 20) or with 1% morphine
      chlorhydrate 0.05 mg kg-1 (n = 20), or bupivacaine alone (n = 20) after surgery
      under general anaesthesia. There were no significant changes in heart rate, blood
      pressure, respiratory rate or oxygen haemoglobin saturation values in all groups,
      and there were no significant differences in the incidence of vomiting and
      pruritus between the groups (P > 0.05). Sedation scores were higher in the
      bupivacaine-midazolam and the bupivacaine-morphine groups than in the bupivacaine
      group at 8-12 h post-operatively (P < 0.01). The durations of analgesia were
      21.15 +/- 1.2 h in the bupivacaine-midazolam group, 14.50 +/- 1.6 h in the
      bupivacaine-morphine group and 8.15 +/- 1.3 h in the bupivacaine group.
      Differences between the bupivacaine-midazolam group and the bupivacaine group (P
      < 0.001), the bupivacaine-midazolam group and the bupivacaine-morphine group (P <
      0.01), and the bupivacaine-morphine group and the bupivacaine group (P < 0.01)
      were significant. It is suggested that caudal administration of a bupivacaine
      midazolam mixture produces a longer duration of post-operative analgesia than a
      bupivacaine-morphine mixture and bupivacaine alone with sedation for 8-12 h post
      operatively.

PMID- 9587724
TI  - Drug interactions and the clinical anaesthetist.
AB  - In clinical practice, anaesthetists encounter many patients who are on concurrent
      medication which may have the potential to interact with drugs used during
      anaesthesia. Many patients are receiving as many as a dozen drugs of various
      kinds, thus, increasing the risk of a drug interaction occurring. Unfortunately
      anaesthetists tend not to report drug interactions which occur during anaesthesia
      -especially those of a minor nature such as flushing--and hence, the true number
      of drug interactions is unknown. We have developed a chart indicating the nature
      of important interactions that the anaesthetist may encounter.

PMID- 9587723
TI  - Anti-emetic efficacy of prophylactic granisetron, droperidol and metoclopramide
      in the prevention of nausea and vomiting after laparoscopic cholecystectomy: a
      randomized, double-blind, placebo-controlled trial.
AB  - This study evaluates the prophylactic anti-emetic efficacy of granisetron,
      droperidol and metoclopramide, for the prevention of post-operative nausea and
      vomiting in female patients undergoing elective laparoscopic cholecystectomy. The
      patients were randomly assigned to one of four groups (n = 30 for each group):
      granisetron 3 mg, droperidol 1.25 mg, metoclopramide 10 mg and placebo (saline).
      These medications were given immediately before the induction of anaesthesia.
      During the first 24 h after anaesthesia, the incidence of post-operative nausea
      and vomiting was 13, 30, 33 and 37% after administration of granisetron,
      droperidol, metoclopramide and placebo, respectively (P < 0.05, overall Fisher's
      exact probability test). No clinically important adverse effects were observed in
      either group. Our results suggest that granisetron is a better anti-emetic than
      droperidol or metoclopramide for the prevention of post-operative nausea and
      vomiting after laparoscopic cholecystectomy when compared with a placebo.

PMID- 9587725
TI  - Post-operative effects of tramadol administered at wound closure.
AB  - The aim of this prospective, randomized and double-blind study was to assess the
      effects of a high dose of the analgesic tramadol administered at the conclusion
      of surgery on extubation time, sedation, and post-anaesthetic shivering. Forty
      adult patients, ASA physical status I or II, underwent laparoscopic surgery of
      about 1 h duration and received a standardized anaesthesia that was maintained
      with isoflurane in O2/N2O. Tramadol 3 mg kg-1 (n = 20) was administered
      intravenously at the beginning of wound closure, and was compared with saline (n
      = 20). Post-anaesthetic shivering did not occur in any patient who received
      tramadol, whereas it occurred in 60% of the control group (P < 0.001). There were
      no adverse effects on time to extubation and sedation, and discharge-ready time
      was shorter in the tramadol group (P < 0.05 compared with control). Pain scores
      in the post-anaesthesia care unit (PACU) were statistically not different between
      the two groups, but significantly more supplemental medication was administered
      in the control group to treat shivering and/or pain. In conclusion,
      administration of a high dose of tramadol at the end of surgery prevents post
      anaesthetic shivering without prolongation of extubation time, and shortens the
      PACU/discharge-ready time.

PMID- 9587726
TI  - Intra-operative evaluation of a continuous versus intermittent bolus
      thermodilution technique of cardiac output measurement in cardiac surgical
      patients.
AB  - The purpose of this study was to analyse the clinical agreement between cardiac
      output measurements, obtained using a newly available continuous thermodilution
      technique, and the conventional intermittent bolus technique. Twenty-four cardiac
      surgical patients were intra-operatively monitored using both techniques.
      Additionally, two different averaging modes for the continuous thermodilution
      technique, either the previous 6 min (group 1) or 3 min (group 2) were compared.
      The mean difference between the continuous thermodilution technique and the
      intermittent bolus technique (bias), were calculated at eight selected time
      points. These ranged from -0.09 to 0.42 litres min-1 in group 1 and from -0.02 to
      0.18 litres min-1 in group 2. There were significant differences at any time
      point between the groups. The relative error between continuous thermodilution
      and intermittent bolus techniques was < 15% for the majority of measurements and
      was significantly higher in group 1 compared with group 2 just prior to
      cardiopulmonary bypass. Thus, the continuous thermodilution technique produced a
      clinically acceptable level of accuracy compared with the intermittent bolus
      technique measurements, especially when using an averaging mode for the previous
      3 min.

PMID- 9587727
TI  - Procalcitonin: a new parameter for the diagnosis of bacterial infection in the
      peri-operative period.
AB  - Procalcitonin, a new innovative inflammation parameter is presently being
      evaluated in clinical studies. It has been shown to be increased markedly in
      patients with severe bacteria induced inflammation, septic shock, endotoxinaemia
      and multiple organ failure. In contrast, severe viral infections or inflammatory
      reactions of non-infectious origin as well as auto-immune or allergic disorders
      do not or only very moderately increase procalcitonin serum levels. Because
      procalcitonin is observed at significantly higher concentrations in bacterial
      infections, it might assist differentiation between these infections and other
      aetiologies of critical illnesses. Furthermore, procalcitonin correlates with the
      severity of infection and sepsis and thus could serve as a useful marker for
      monitoring surgical high risk patients. Procalcitonin may serve as a valid and
      sensitive indicator for bacterial infection with important diagnostic potential
      in the peri-operative period and in intensive care medicine.

PMID- 9587728
TI  - Patient-controlled sedation during transvaginal oocyte retrieval: an assessment
      of patient acceptance of patient-controlled sedation using a mixture of propofol
      and alfentanil.
AB  - Patient-controlled sedation (PCS) has been used during many different surgical
      procedures, both alone and as an adjunct to local or regional anaesthesia.
      Sedation with an admixture of propofol and alfentanil during transvaginal oocyte
      retrieval has been used successfully in this unit and this study was performed to
      assess the degree of patient acceptance of patient-controlled sedation, as other
      studies have indicated that self-administration of sedation may confer additional
      benefits on the patient, unrelated to the choice of sedation agent. An admixture
      of 50 mL propofol 1% with alfentanil 2 mg was loaded into a Graseby 3300 patient
      controlled analgesia pump and administered as increments of 0.3 mL with a zero
      lock-out interval. This method of sedation provided safe and highly satisfactory
      sedation for this group of patients with 55 of 56 patients indicating that they
      would opt for this type of sedation again. There was a very low incidence of over
      sedation, and this sedation method is likely to produce a relaxed and co
      operative patient for a wide variety of surgical procedures.

PMID- 9587729
TI  - 5-Hydroxytryptamine potentiates post-tetanic twitch responses in the rat phrenic
      nerve diaphragm preparation.
AB  - 5-Hydroxytryptamine has wide-ranging effects on a number of physiological
      systems. In addition the exogenous application of 5-hydroxytryptamine or 5
      hydroxytryptamine type drugs to tissue bath preparations has revealed the
      presence of a large and ever growing population of 5-hydroxytryptamine receptors.
      The discovery that 5-hydroxytryptamine is released at the neuromuscular junction
      raises the question as to whether it has a physiological function and whether or
      not applying low concentrations of 5-hydroxytryptamine transmitter would have any
      significant effect on twitch response at different rates of stimulation. Previous
      studies have demonstrated both facilitatory and depressant effects upon twitch
      responses in a variety of animal models. Single twitch responses of the rat
      phrenic nerve diaphragm preparation at non-fatiguing (0.3 Hz) and tetanic rates
      of stimulation (50 Hz) were recorded under conditions of indirect (nerve)
      stimulation at 4 g resting tension. The preparation was incubated with 0.5, 1, 2,
      4, 16 mumol litre-1 concentrations of 5-hydroxytryptamine. The results of our
      investigations demonstrate that while low concentrations of 5-hydroxytryptamine
      have no effect upon the single twitch response at resting rates of stimulation
      (0.3 Hz), the initial single twitch and the subsequent eighteen responses
      immediately following a tetanus are facilitated (P < 0.05). This work
      demonstrates that 5-hydroxytryptamine does have significant effects upon the
      neuromuscular junction under conditions of physiological compromise (following
      tetanus). These observations are the first step, therefore, in a series of
      studies aimed at identifying the resident 5-hydroxytryptamine receptors within
      the neuromuscular junction which will subsequently enable us to predict
      therapeutic effect or toxicity.

PMID- 9587731
TI  - Charcoal as an airway isoflurane reflection filter.
AB  - The isoflurane-saving and CO2-retaining effects of a charcoal filter were
      compared with a Siemens standard heat and moisture (HME) exchanger and an emptied
      specimen (dummy). Isoflurane was delivered during the inspiratory phase and
      consumption investigated at 10, 15 and 25 cycles min-1. The investigation was
      performed by ventilation with humidified air with a constant end-tidal CO2 and
      temperature. For a comparison, isoflurane was delivered in a conventional manner
      via the ventilator. The arrangement with a charcoal filter reduced the isoflurane
      consumption by a factor of 2.0-2.6, depending on ventilatory rate. Most of the
      saving was a result of the method of isoflurane delivery (factor 1.4-2.0), while
      adding the reflector gave a further reduction (factor 1.3-1.5). One circumstance
      that reduced the net efficiency of the charcoal filter was that it also reflected
      CO2; consequently, total minute ventilation had to be increased to maintain
      constant end-tidal CO2.

PMID- 9587730
TI  - Isoflurane reduces synaptic glutamate release without changing cytosolic free
      calcium in isolated nerve terminals.
AB  - The molecular mechanism of volatile anaesthetic action on presynaptic glutamate
      release is not clear. An inhibitory effect on voltage-gated calcium channels has
      been proposed. The present study examines the effect of isoflurane on cytosolic
      free calcium and synaptic glutamate release from isolated nerve terminals.
      Synaptosomes from rat cerebral cortex were used. Glutamate was measured with a
      continuous fluorometric measurement in a spectrophotometer as the fluorescence of
      NADPH and calcium as the fluorescence of fura-2. Isoflurane reduced the calcium
      dependent glutamate release evoked by membrane depolarization with 4
      aminopyridine in an inversely dose-dependent manner. The glutamate release was
      reduced by 56, 43 and 36% in response to isoflurane 0.5, 1.5 and 3.0%,
      respectively (for all: P < 0.05). Membrane depolarization evoked a rise in
      cytosolic free calcium of approximately 34%. Addition of isoflurane (0.5, 1.5 and
      3.0%) produced no significant change in cytosolic free calcium. These results
      indicate that the isoflurane-induced reduction in presynaptic glutamate release
      is caused by other mechanisms than blocking voltage-gated calcium channels. As
      the release is inversely dose-dependent, two or more mechanisms could be
      involved.

PMID- 9587732
TI  - Inadequate tourniquet inflation associated with a case of prilocaine toxicity.
AB  - A 74-year-old woman was scheduled for surgical treatment of a carpal tunnel
      syndrome. An intravenous (i.v.) regional anaesthetic was performed using 1%
      prilocaine standard technique. Three minutes after injection of the local
      anaesthetic mild to moderate central nervous system symptoms developed, along
      with tachycardia, sweating and peri-oral paraesthesia. The evolution was
      favourable, no convulsions or other more serious events occurred. Despite showing
      adequate pressure inflation the tourniquet failed to accomplish its purpose. The
      patient recovered well without any sequelae.

PMID- 9587733
TI  - Fibreoptic intubation through a laryngeal mask airway in an infant with Robin
      sequence.
AB  - Airway management is a major concern in Robin sequence, where micrognathia,
      glossoptosis and a cleft of the soft palate exist. The management of an infant
      with a potentially difficult airway is discussed where tracheal intubation was
      aided by the use of a 2.2-mm fibrescope mounted with a 3-mm endotracheal tube
      passed through a size 1 laryngeal mask airway.

PMID- 9587734
TI  - Suxamethonium-induced cardiac arrest and death following 5 days of
      immobilization.
AB  - The present report describes a case of cardiac arrest and subsequent death as a
      result of hyperkalaemia following the use of suxamethonium in a 23-year-old
      Malawian woman. Five days after the onset of the symptoms of meningitis, the
      patient aspirated stomach contents and needed endotracheal intubation. Forty
      seconds after injection of suxamethonium, bradycardia and cardiac arrest
      occurred. Attempts to resuscitate the patient were not successful. The serum
      level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in
      the patient's level of consciousness, there were no signs of motor neurone damage
      or of any of the other known predisposing conditions for hyperkalaemia following
      the administration of suxamethonium. It is postulated that her death was caused
      by hypersensitivity to suxamethonium, associated with her 5-day immobilization.

PMID- 9587736
TI  - Cardiac tamponade during laparoscopic Nissen fundoplication.
AB  - Laparoscopic Nissen fundoplication is becoming a popular technique in the
      surgical management of reflux disease. The advantages of laparoscopic surgery
      include shorter hospital stays, greater patient acceptance and decreased overall
      morbidity. Laparoscopic surgery eliminates the necessity for an upper abdominal
      incision and the consequent post-operative impairment of pulmonary mechanics.
      Laparoscopic Nissen fundoplication has been associated with a low incidence of
      severe peri-operative complications although of a different nature to those
      following the open procedure. We are reporting a rare case of acute
      cardiovascular collapse secondary to cardiac tamponade during laparoscopic Nissen
      fundoplication.

PMID- 9587735
TI  - Management of a patient with familial amyloid polyneuropathy type I with lumbar
      epidural anaesthesia.
AB  - Familial amyloid polyneuropathy (FAP) type I is a rare disease characterized by
      sensorimotor polyneuropathy, and autonomic nervous system and cardiac conduction
      system dysfunction. Severe bradyarrhythmia and hypotension may occur during
      anaesthesia and surgery in patients with the FAP type I. Only one report has been
      published of a patient with FAP type I who was managed with epidural anaesthesia.
      The present authors report a 38-year-old Japanese man with a permanent pacemaker
      because of advanced FAP type I who underwent rotation flap of the gluteus maximus
      muscle to cover a trophic ulcer in the sacral region under lumbar epidural
      anaesthesia. Ten millilitres of adrenaline (1:200,000) was injected around the
      ulcer prior to surgical manipulation. Neither bradycardia nor hypotension
      developed during the procedures. The haemodynamic changes under lumbar epidural
      anaesthesia in FAP type I are discussed.

PMID- 9587737
TI  - Laryngeal function may be impaired in patients with cervical osteophytes.

PMID- 9587738
TI  - Polymorphism within the HLA-DQB1*02 promoter associated with susceptibility to
      coeliac disease.
AB  - Susceptibility to coeliac disease is associated with a particular HLA-DQ alpha
      beta heterodimer encoded by the DQA1*0501 and DQB1*02 genes. A single base
      polymorphism in the DQB1*02 promoter region in DR7, DQA1*0201, DQB1*02 haplotypes
      was observed, associated with an increased susceptibility to the disease. This
      finding suggests a novel mechanism of susceptibility to immune-mediated diseases.

PMID- 9587739
TI  - HLA class II allele and haplotype distribution in a population from central
      Poland.
AB  - We have studied the distribution of HLA DRB1, DQA1, DQB1 alleles and haplotypes
      in a sample of 103 unrelated healthy individuals from the region of Lodz in
      central Poland by the polymerase chain reaction and hybridization with allele
      specific oligonucleotide probes (PCR-SSO). DRB1*0101, DRB1*07, DRB1*1501, DRB1*03
      and DRB1*11 were the most frequent alleles at the DRB1 locus. The DRB1*04 group
      was observed at a high frequency, but only five out of the 19 DR4 subtypes tested
      were observed. The most frequent was DRB1*0401, followed by DRB1*0403, DRB1*0402,
      DRB1*0407 and DRB1*0417. Eight DQA1 alleles were found in this Polish population,
      among which DQA1*0501, DQA1*0101 and DQA1*0102 were the most frequent. At the
      DQB1 locus 13 alleles were found. Among them, four were present with frequencies
      above 10%: DQB1*0201, DQB1*0301, DQB1*0501 and DQB1*0602. Our results underline
      significant differences between the population of central Poland and populations
      of neighbouring countries such as Germany, Ukraine and the Czech Republic. This
      study will serve as a reference for further anthropological studies, as well as
      studies of associations between HLA and disease.

PMID- 9587741
TI  - A nested PCR-RFLP method for high-resolution typing of HLA-A alleles.
AB  - We developed a nested polymerase chain reaction (PCR) restriction fragment length
      polymorphism (RFLP) method for high-resolution typing of HLA-A alleles. HLA-A
      alleles can be identified by this method without the need for other information
      such as serological type. The first PCR was performed using outer primers, ASP5
      and ASP3, specific for the HLA-A gene, and a 991-bp DNA fragment extending from
      exon 1 through exon 3 was amplified. In the second PCRs, exon 2 and exon 3 of the
      HLA-A gene were amplified separately from the diluted first PCR product using
      nested primers. Computer analysis of cleavage patterns for 78 HLA-A alleles
      showed that 31 RFLP patterns could be obtained by digestion of the exon 2 PCR
      product using eight restriction endonucleases and 42 RFLP patterns by digestion
      of the exon 3 PCR product using 11 restriction endonucleases, and all alleles
      could be discriminated based on combinations of these RFLP patterns except for
      nine allele groups or pairs: A*0201/0207/0215N/0220/0222, A*0205/0208/0214,
      A*0206/0221, A*0212/0213, A*2402/2405, A*2406/2413, A*2601/2605, A*2603/2606 and
      A*7401/7402. Thus, 65 PCR-RFLP patterns were predicted from the results of
      analysis of digestion patterns of 78 HLA-A alleles. Among 2145 possible
      homozygous and heterozygous combinations of the 65 distinguishable PCR-RFLP
      patterns, 82 combinations were predicted to have the same PCR-RFLP patterns. In
      PCR-RFLP analysis, although the nested primers were not specific for the HLA-A
      gene, clear RFLP banding patterns were obtained because specificity was
      guaranteed by the use of the outer primers, ASPS and ASP3 in the first PCR.
      A*0201 and A*0207 occur relatively frequently in the Asian populations among
      indistinguishable allele groups or pairs using the present PCR-RFLP method. We
      also developed a PCR sequence-specific primers (PCR-SSP) method for
      distinguishing between A*0201/0220/0222 and A*0207/0215N. We could identify 39
      alleles (groups) upon HLA-A typing of 50 Japanese individuals, 40 cell lines of
      the Fourth Asia-Oceania Histocompatibility Workshop, and 80 cell lines of the
      UCLA International Cell Exchange Program using the present PCR-RFLP and PCR-SSP
      methods.

PMID- 9587740
TI  - HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic
      patients.
AB  - To further substantiate reports of an association between the major
      histocompatibility complex subtypes and clozapine-induced agranulocytosis, HLA
      typing was performed in 61 Jewish Israeli schizophrenic patients, in 11 of whom
      agranulocytosis developed following clozapine treatment and in 50 (controls) of
      whom it did not. Of the 11 agranulocytosis patients, seven (63%) were of
      Ashkenazi origin and four (37%) of Sephardi origin. There was no difference in
      ethnic origin between the arganulocytosis and non-agranulocytosis groups (chi 2 =
      2.4, d.f. = 1, P = 0.11), although the agranulocytosis patients had a higher
      frequency of the HLA B38 antigen (8/11 or 72% vs. 6/50 or 12%; chi 2 = 18.7, d.f.
      = 1, P < 0.001). These results suggest that major histocompatibility complex gene
      products could be involved in clozapine-mediated haematological complications.

PMID- 9587742
TI  - Routine HLA-B27 typing by flow cytometry: differentiation of the products of HLA
      B*2702, B*2705 and B*2708.
AB  - Patient HLA-B27 typing is widely performed as an aid to the diagnosis of several
      diseases, particularly ankylosing spondylitis. Typing by flow cytometry, using
      monoclonal antibodies, has been shown to be a potentially useful alternative to
      classical serology on account of its speed, simplicity and economy. However, we
      required a flow cytometry typing procedure that would accurately differentiate
      HLA-B27 (Bw4) from B2708 (Bw6) and not be confounded by other HLA-B7/B27 cross
      reactive group antigens. Accordingly, we evaluated the simultaneous use of two
      monoclonal antibody preparations, ABC-m3-FITC (anti-B27 + weak B7)/BB7.1-PE (anti
      B7) and FD705-FITC (anti-B27), by testing a highly selected panel of 62 reference
      lymphocytes containing examples of all HLA-B7/B27 cross-reactive group antigens,
      including: HLA-B42, B47, B48, B73, B703, B2702, B2705 and B2708. In addition, 268
      whole blood samples from routine patient requests for B27-associated disease
      typing were tested in parallel with HLA-B typing using the standard complement
      dependent microlymphocytoxicity test. The detailed specificity of the three
      monoclonal antibodies was established and the products of HLA-B*2702, B*2705 and
      B*2708 were found to be readily differentiated from each other and all other HLA
      B7/B27 cross-reactive HLA-B antigens.

PMID- 9587743
TI  - TNFB gene polymorphism in insulin-dependent diabetes mellitus: association with
      HLA-DR alleles.
AB  - A polymorphism of the TNF-beta gene can be detected by restriction digestion of a
      PCR product with NcoI. In this study we look at the risk associated with this
      polymorphism in a study of 69 insulin-dependent diabetes patients and 119 healthy
      controls. The risk was further characterized by comparison to the HLA type of the
      individual, since the TNF polymorphism is in linkage disequilibrium with HLA
      genes.

PMID- 9587744
TI  - Nomenclature for factors of the HLA system, update November/December 1997.

PMID- 9587745
TI  - The German teleradiology system MEDICUS: system description and experiences in a
      German field test.
AB  - MEDICUS is a teleradiology system which has been developed in a joint project of
      the German Cancer Research Center (Deutsches Krebsforschungszentrum) and the
      Transfer Center Medical Informatics (Steinbeis-Transferzentrum Medizinische
      Informatik) in Heidelberg, Germany. The system is designed to work on ISDN lines
      as well as in a local area network. Special attention has been given to the
      design of the user interface and data security, integrity, and authentication.
      The software is in use in 13 radiology departments in university clinics, small
      hospitals, private practices, and research institutes. More than 25 thousand
      images have been processed in 6 months. The system is in use in six different
      application scenarios. MEDICUS is running under the UNIX operating system. The
      connection of the modalities could in most cases not be realized with the DICOM
      protocol as older machines were not equipped with this standard protocol.
      Clinical experiences show that the MEDICUS system provides a very high degree of
      functionality. The system has an efficient and user friendly graphical user
      interface. The result of a comparison with other systems shows that MEDICUS is
      currently the best known teleradiology system. Cost reductions are already
      obvious, but additional research has to be performed in this field. An even more
      powerful commercial successor is currently under construction at the Steinbeis
      Transferzentrum Medizinische Informatik in Heidelberg.

PMID- 9587747
TI  - Image quality of spiral CT versus conventional CT in routine brain imaging.
AB  - OBJECTIVE: Aim of the study was to compare image quality of spiral (helical)
      versus conventional (sequential) routine brain scans obtained on a spiral CT
      scanner of the latest generation. MATERIALS AND METHODS: In a prospective study
      60 patients scheduled for cranial CT were examined in spiral (27 cases) or
      conventional technique (33 cases) after randomization. Two blinded observers
      rated artifacts, gray--white-matter contrast and overall image quality. RESULTS:
      No significant differences in artifacts were detected. Concerning gray--white
      matter contrast and overall image quality, none or small differences in favour of
      conventional scans were found depending on the observer. CONCLUSION: On a modern
      scanner image quality of spiral brain scans in adults is nowadays comparable to
      or only slightly less than that of conventional scans. On such a machine, spiral
      mode can be recommended if, for example, rapid scanning or high-quality secondary
      reconstructions are needed.

PMID- 9587746
TI  - Comparative assessment of digital and analog radiography: diagnostic accuracy,
      cost analysis and quality of care.
AB  - OBJECTIVE: The aim of this study was to compare digital and conventional
      radiography for diagnostic accuracy, direct costs, and quality of care. MATERIALS
      AND METHODS: Diagnostic accuracy was assessed by a critical review of the
      literature on sensitivity, specificity and ROC analysis of these imaging
      techniques and by a survey with a panel of radiologists. Direct costs and quality
      of care were evaluated with a before/after study of the implementation of digital
      radiography in a Department of Radiology in 'Hospices Civils de Lyon' (France).
      We included 292 patients and measured duration of examinations and direct costs
      of equipment, films, maintenance and depreciation. To evaluate any changes in
      working conditions and patient management, a questionnaire was filled out by the
      staff of the department. RESULTS: Diagnostic accuracy with digital radiography
      was equivalent to that of conventional radiography but there were wide variations
      depending on the type of examination. In 1993, although digital radiography
      resulted in savings of FF 18,000 including tax (US$ 3600) on film consumption for
      1 year of examinations, there was a global additional cost of FF 253,000 (US$
      50,600) for maintenance and depreciation. Results showed a nonsignificant
      tendency to reduced procedure times for all examinations. Working conditions
      improved, including greater availability for the patient, improved safety, and
      increased job interest. CONCLUSION: Digital radiography can be introduced into a
      large hospital to improve patient and staff conditions, at a higher cost than
      analog radiography, and depending on the type of examinations performed by the
      radiology department.

PMID- 9587748
TI  - Metastatic rhabdomyosarcoma presenting as intracranial hemorrhage: imaging
      findings.
AB  - The CNS is rarely the first site of metastasis for rhabdomyosarcoma. CNS
      involvement is uncommon, and usually seen as leptomeningeal spread after
      development of pulmonary metastases. We present the imaging findings in a 13-year
      old boy in whom a large intracranial hemorrhage was the initial presentation of
      surgically documented metastatic prostatic rhabdomyosarcoma. Multiple chest CTs
      and radionuclide bone scans had previously shown no evidence of pulmonary or
      osseous metastases. The significance of this case in relation to the possible
      role of the need for use of chemotherapeutic agents that cross the blood-brain
      barriers to prevent brain metastasis is discussed.

PMID- 9587749
TI  - Disseminated thrombosis in primary antiphospholipid syndrome: MR findings.
AB  - We report the MR imaging findings in a patient with primary antiphospholipid
      syndrome, adrenal infarction and widespread thrombosis involving abdominal,
      pelvic, and pulmonary vessels. This syndrome should be suspected in patients with
      thromboses and organ infarctions of otherwise undetermined etiology.

PMID- 9587750
TI  - Bilateral, tumorlike diabetic mastopathy-progression and regression of the
      disease during 5-year follow up.
AB  - Diabetic mastopathy is a recently described collection of radiographical and
      histological features found in dense fibrous masses of the breast in long
      standing Type I diabetes. We describe the first case of bilateral disease with
      the alternate progression and regression of the disease over a 5 year period. A
      45-year-old woman has been affected of insulin dependent diabetes mellitus (IDDM)
      for 21 years. She developed palpable mass retromamillar of the right side,
      indistinguishable radiographically from cancer. The histology showed a diabetic
      mastopathy (DMP) with B-lymphocytic ductitis and lobulitis, a discrete
      monocellular vasculitis and a keloid-like fibrosis. After 22 months she developed
      a suspicious palpable mass contralateral on the left side. The FNAB presented an
      identical morphology on histology. Additionally 10 months later there were no
      palpable masses of both mammae. Mammographically no suspect alterations were
      observed. One year later the clinical and mammographical examination showed
      similar findings, mentioned before. The pathogenesis is still obscure and
      includes the hypothesis of extracellular accumulation, secondary to prolonged
      hyperglycemia in IDDM, production of alternated non-enzymatic glycosylated end
      products with neoantigen formation, B cell predominant inflammation with
      autoimmune response against neoantigens and cytokine release secondary to the
      autoimmune response.

PMID- 9587751
TI  - Systematic ultrasonography in asymptomatic dense breasts.
AB  - The purpose of this study was to evaluate the role of ultrasonography in breast
      cancer screening. 350 Bilateral ultrasound (US) were performed in 350
      asymptomatic patients with dense breasts. 7.5, 10 And 13 MHz transducers were
      used (Esaote Biomedica, Italy). In 185/350 patients, sonograms were normal,
      abnormalities were seen in 165/350: cysts (117), solid nodules (44) and mixed
      echogenicity nodules (4). All but two solid lesions were benign. Both malignant
      lesions were invasive carcinomas, 18 and 11 mm in diameter. In retrospect, they
      were palpable, but not visible on mammograms. Retroprospective review revealed
      that 24.7 of cysts and 31% solid nodules could be seen on mammograms. In 4
      patients with fibroadenomas, US made a false positive diagnosis of breast cancer.
      Follow-up was obtained for 6 to 18 months in 45% of patients. Routine
      supplemental US evaluation for patients with mammographically dense breasts does
      not appear to significantly contribute to the accuracy of the work-up.

PMID- 9587752
TI  - Multiple single sections Turbo FLASH MR arterial portography in the detection of
      hepatic neoplasms.
AB  - OBJECTIVE: To determine the sensitivity of multiple single sections Turbo FLASH
      MR arterial portography (MRAP) in the detection of hepatic neoplasms. METHODS AND
      PATIENTS: Twelve patients with hepatic mass underwent MRAP prior to hepatic
      resection. Findings of MRAP were compared with surgical specimen and intra
      operative ultrasonography (US). RESULTS: A total of 19 separate malignant
      neoplastic nodules were identified in the resected specimens or intra-operative
      ultrasonography. The sensitivity was 89.5% (17/19) for MRAP. MRAP depicted all
      neoplasms more than 1.0 cm in diameter. Two lesions not depicted on MRAP had a
      diameter of 5 and 9 mm, respectively. One lesion identified by MRAP was confirmed
      to false positive lesion by intra-operative US. CONCLUSION: Multiple single
      sections Turbo FLASH MRAP may be a valuable adjunct for pre-operative detection
      of malignant hepatic neoplasms.

PMID- 9587753
TI  - Radiological evaluation of complications of intestinal tuberculosis.
AB  - Complications of intestinal tuberculosis may be masked. This study aims to
      heighten awareness of these unusual clinical complications and the radiological
      findings in such cases. Over a period of 5 years, 21 patients with proven
      intestinal tuberculosis, 13 of whom presented with complications, are presented
      in this report. Radiological diagnosis was by barium gastrointestinal studies and
      computed tomographic (CT) evaluation. Surgical specimens and histopathology
      confirmed the diagnosis. The commonest complication was intestinal obstruction (N
      = 6). Others were esophagobronchial and duodenocolic fistulas (N = 2),
      significant gastrointestinal hemorrhage (N = 3) caused by ulcers in the small
      bowel and colon, and malabsorption syndrome (N = 3) caused by diffuse small bowel
      infiltration in 2 cases and duodenocolic fistula in the third case. None of the
      patients presented were immunocompromised. Though uncommon, tuberculosis should
      be considered in patients presenting clinically with intestinal obstruction,
      significant gastrointestinal hemorrhage and malabsorption state.

PMID- 9587754
TI  - Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis--a case
      report.
AB  - Steroid cell tumors of the ovary are rare sex-cord neoplasms which account for
      less than 0.1% of all ovarian tumors. They have been divided into two subtypes
      according to their cell of origin as follows: stromal luteoma, and Leydig cell
      tumors, and a third subtype with lineage unknown is a steroid cell tumor, not
      otherwise specified (NOS). The clinical presentation may take many forms,
      including pain, abdominal distention and bloating, but perhaps the most
      interesting and noticeable presentations are those related to the hormonal
      activity and virilizing properties of the tumor. No radiological features of the
      steroid cell tumor, NOS have been presented in the literature. This report
      presents the MRI and ultrasonographic findings of a patient having steroid cell
      tumor, NOS, of the right ovary with metastasis to the uterus.

PMID- 9587755
TI  - Transvaginal sonography in endometrial carcinoma: preoperative assessment of the
      depth of myometrial invasion in 50 cases.
AB  - OBJECTIVE: A prospective study was designed for patients previously diagnosed of
      endometrial carcinoma to evaluate the accuracy of transvaginal sonography (TVS)
      in determining both the presence and the depth of myometrial invasion. Patients
      with advanced stage disease (III and IV) were specifically excluded from the
      analysis. SUBJECTS AND METHODS: Sixty patients with endometrial carcinoma
      underwent transvaginal ultrasonography. Ten of these patients were ruled out due
      to various reasons. In the remaining 50 cases, TVS findings were compared with
      those obtained after total abdominal hysterectomy and bilateral salpingo
      oophorectomy (AHT). RESULTS: The sensitivity of TVS in detecting deep invasion,
      i.e. more than 50% of the myometrial thickness was 94.1%, while the specificity
      was 84.8% and the overall accuracy was 88%. Following the classification of the
      International Federation of Obstetrics and Gynecology, stage I, which divides
      myometrial invasion into three categories (none, superficial involvement and deep
      invasion) sensitivity was 66.2%, specificity was 83.1% and overall accuracy was
      77.2%. CONCLUSION: These findings are consistent with those reported in
      literature with regard to overall accuracy of TVS. Results are similar to those
      obtained with magnetic resonance imaging (MRI) without contrast and slightly
      lower than MRI plus contrast.

PMID- 9587756
TI  - Multiple lower limb non-ossifying fibromas in siblings with neurofibromatosis.
AB  - Non-ossifying fibromas are common benign lesions of tubular long bones. There is
      recognized association of these bony lesions with neurofibromatosis type 1
      although the presence of non-ossifying fibromas in familial members with the
      condition has not previously been reported. We report two siblings with
      neurofibromatosis and radiological evidence of multiple lower limb non-ossifying
      fibromas. Both patients presented with pain in the knees and a pathological
      fracture was observed in one case. Patients with multiple non-ossifying fibromas
      should be examined carefully for other evidence of neurofibromatosis.

PMID- 9587757
TI  - Pseudotumor formation in tibia in Gaucher's disease.
AB  - A very rare case of type 1 Gaucher's disease with pseudotumor formation in the
      right tibia is presented. In addition to the characteristic radiographic finding
      of distal femoral flaring (Erlenmeyer flask deformity), a lobulated osteolytic
      area with surrounding sclerosis was seen in the proximal metaphysis of the right
      tibia. Adjacent to this pseudotumor appearance was an old pathologic fracture and
      no significant soft tissue swelling was evident, both of these features being
      reported for the first time in association with Gaucher's disease.

PMID- 9587758
TI  - Emphysematous pyelonephritis: fatal outcome during percutaneous drainage.

PMID- 9587759
TI  - Normal bladder wall morphology in Gd-DTPA-enhanced clinical MR imaging using an
      endorectal surface coil and histological assessment of submucosal linear
      enhancement using [14C]Gd-DOTA autoradiography in an animal model.
AB  - OBJECTIVE: The purpose of this study was to investigate normal bladder wall
      morphology in gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced
      magnetic resonance (MR) imaging using an endorectal surface coil and to perform
      histological assessment of submucosal linear enhancement with experimental [14C]
      gadolinium-tetraazacyclododecane-tetraacetic acid (Gd-DOTA) autoradiography.
      METHODS AND MATERIAL: MR imaging of the bladder was performed using an endorectal
      coil in 13 consecutive patients with bladder carcinoma and T1-, T2-, and Gd-DTPA
      enhanced spin-echo images of the bladder wall were compared. After injection of
      [14C]Gd-DOTA into a hamster, autoradiograms of the bladder wall were obtained and
      compared with serial histological sections. RESULTS: The normal bladder wall
      appeared as a homogeneous layer of intermediate intensity on T1-weighted images.
      After administration of Gd-DTPA, the bladder wall was visualized as three layers:
      an inner thin layer of low intensity, a middle layer of marked enhancement, and a
      thick outer layer of intermediate intensity. The autoradiograms demonstrated
      dense accumulation of [14C]Gd-DOTA in the submucosal layer. Thus, the inner,
      middle, and outer layers corresponded to the mucosa, submucosa, and muscularis
      propria, respectively. The thickness of the bladder wall demonstrated on T2
      weighted images was almost equal to that of the outer layer on enhanced T1
      weighted images. Thus, T2-weighted images revealed only the muscle layer as an
      intermediate-intensity band. In the preliminary clinical study, MR imaging
      invariably showed accurate stages of the bladder carcinoma in 13 patients.
      CONCLUSION: In MR imaging of the normal bladder wall, the submucosa was
      strikingly enhanced after Gd-DTPA administration, separating the bladder wall
      into three layers. This may have a potential role in the staging of bladder
      tumors.

PMID- 9587760
TI  - Can the IVIM model be used for renal perfusion imaging?
AB  - OBJECTIVE: Renal perfusion imaging may provide information about the hemodynamic
      significance of a renal artery stenosis and could improve noninvasive
      characterization when combined with angiography. It was proposed previously that
      diffusion sequences could provide useful perfusion indices based on the
      intravoxel incoherent motion (IVIM) model. Owing to motion artifacts, diffusion
      imaging has been restricted to relatively immobile organs like the brain. With
      the availability of single-shot echo-planar imaging (EPI) our purpose was to
      evaluate the IVIM model in renal perfusion. METHODS AND MATERIAL: Eight
      volunteers underwent diffusion-sensitive magnetic resonance (MR) imaging of the
      kidneys using a spin echo (SE) EPI sequence. The diffusion coefficients
      determined by a linear regression analysis and fits to the IVIM function were
      calculated. RESULTS AND CONCLUSION: Our preliminary experience does not support
      the possibility of obtaining perfusion information using the IVIM model in the
      kidneys.

PMID- 9587761
TI  - Percutaneous long-term arterial access with implantable ports. Direct subclavian
      approach with US.
AB  - PURPOSE: To clarify the clinical feasibility of getting a long-term arterial
      access at the subclavian region by directly puncturing the artery under
      ultrasound guidance. MATERIALS AND METHODS: Percutaneous placements of arterial
      infusion catheters with implantable ports were performed in 30 patients with
      malignant abdominal tumors. The axillary artery in the subclavian region was
      punctured directly with an 18G needle under ultrasound guidance. Using the
      Seldinger technique, a 5Fr catheter was placed with its tip in the hepatic or the
      other tumor-supplying arteries. The catheter was connected to an implantable
      port, and both of them were embedded in the subcutaneous pocket. RESULTS:
      Percutaneous placements of infusion catheters were successfully performed in 29
      cases. Transarterial chemotherapy through implanted ports was done uneventfully
      in 26 patients, while in the other three cases, catheter dislodgment occurred.
      Two local haematomas, one wound infection and one cerebellar infarction were also
      experienced. CONCLUSION: Ultrasound-guided subclavian approach is a minimally
      invasive way of implanting an infusion catheter for chemotherapy, although its
      indication for severely atherosclerotic patients should be limited.

PMID- 9587762
TI  - Preoperative localization of a foreign body by magnetic resonance imaging.
AB  - Nonradioopaque foreign bodies are very difficult to detect and localize. A case
      is presented in which a retained palm tree thorn was visualized and extracted
      with the help of magnetic resonance imaging.

PMID- 9587763
TI  - Portable-type stereo fluoroscope for surgery.
AB  - A prototype of a portable stereo fluoroscope was devised. This system has two X
      ray tubes and one image intensifier. To create a three-dimensional view, the
      system alternately exposes the X-ray from left and right X-ray tubes 15 times per
      second (7.5 pairs/s) to obtain left and right eye images with parallax. Each
      image is stored in video-RAM (random access memory) and left and right images are
      alternately displayed on a monitor at 120 frames/s (60 pairs/s). A liquid crystal
      modulator mounted on the monitor and special polarizing glasses worn by the
      surgeon convey the appropriate image to the proper eye. It was applied in a
      simulation of interlocking intramedullary nails and fixation of femoral neck
      fracture using phantom femurs. The three-dimensional view in real-time makes it
      easy to understand the shape of the bone phantom and to determine the spatial
      relationship between it and the instruments used without moving the C-arm.

PMID- 9587764
TI  - Venous chest anatomy: clinical implications.
AB  - This article provides a practical approach to the clinical implications and
      importance of understanding the collateral venous anatomy of the thorax. Routine
      radiography, conventional venography, computed tomography (CT), and magnetic
      resonance (MR) imaging studies provide correlative anatomic models for the
      demonstration of how interconnecting collateral vascular networks within the
      thorax maintain venous stability at all times. Five major systems comprise the
      collateral venous network of the thorax (Fig. 1). These include the
      paravertebral, azygos-hemiazygos, internal mammary, lateral thoracic, and
      anterior jugular venous systems (AJVS). The five systems are presented in the
      following sequence: (a) a brief introduction to the importance of catheter
      position and malposition in understanding access to the thoracic venous system,
      (b) the anatomy of the azygos-hemiazygos systems and their relationship with the
      paravertebral plexus, (c) the importance of the AJVS, (d) 'loop' concepts
      interconnecting the internal mammary and azygos-hemiazygos systems by means of
      the lateral thoracic and intercostal veins, and (e) the interconnecting venous
      networks on the thoracic side of the thoracoabdominal junction. Certain aspects
      of the venous anatomy of the thorax will not be discussed in this chapter and
      include (a) the intra-abdominal anastomoses between the superior and inferior
      vena cavae (IVC) via the internal mammary, lateral thoracic, and azygos
      hemiazygos systems (beyond the scope of this article), (b) potential collateral
      vessels involving vertebral, parascapular, thyroidal, thymic, and other smaller
      veins that might anastomose with the major systems, and (c) anatomic variants and
      pitfalls that may mimic pathologic conditions (space limitations).

PMID- 9587765
TI  - The azygos lobe: normal variants that may simulate disease.
AB  - In this paper we describe the normal appearance of the azygos lobe on
      conventional radiography and CT, presenting variants that may simulate pathology
      on the chest radiograph. We describe the signs that allow identification of such
      variants and the role of CT in explaining the findings and excluding a
      pathological process.

PMID- 9587766
TI  - Diagnostic approach to mediastinal masses.
AB  - Mediastinal masses represent a vast group of tumours and pseudo-tumours which can
      involve the various compartments of the mediastinum. The authors propose a
      radiologic diagnostic approach starting from the plain thoracic radiograph with
      study of the mediastinal lines and oesophageal transit and going on to the
      classifications made possible by modern CT and MR imaging. The proposed
      diagnostic procedure is based on nine mediastinal lines and two 'threads of
      Ariadne' which are the compartments where the masses are located and their
      behaviour at CT (densitometry before and after administration of an iodinated
      bolus) and at MRI (T1, T2, gadolinium-enhanced T1-weighted sequences). The
      definitive aetiological diagnosis may be established by surgery, but also in
      certain cases by percutaneous needle biopsy.

PMID- 9587767
TI  - Common and uncommon complications of reactivation tuberculosis in immunocompetent
      patients.

PMID- 9587768
TI  - Technical aspects of twin screen-film chest radiography: cost effective lung and
      mediastinal imaging.
AB  - OBJECTIVE: To determine the sensitometry and 'cross-talk' of a twin screen-film
      cassette and to assess its clinical potential. MATERIALS AND METHODS: The twin
      cassette utilises two sets of screens, divided by filter material, to provide an
      optimised image of the mediastinum and the lungs. The exposure difference for the
      two images was measured sensitometrically. The contribution to film density of
      visible light and K-characteristic radiation, from adjacent screens in the
      absence of a dividing filter, was investigated. RESULT: Clinical experience
      indicated that an exposure difference of 3.4 between the front and back screens,
      was optimal. Visible light and K-characteristic radiation from the front screens,
      contributed up to 20 and 24% respectively, of the back film exposure and screen
      absorbed energy respectively. This was reduced to 0 and 6% with the use of the
      filter. CONCLUSIONS: The twin screen-film cassette provides extended latitude to
      enable optimal visualisation of the lung and mediastinal regions. Adjacent screen
      'cross-talk' has been overcome to allow standard and portable chest applications.

PMID- 9587769
TI  - Clinical evaluation of twin screen-film chest radiography: cost effective lung
      and mediastinal imaging.
AB  - OBJECTIVE: A new twin screen-film cassette system optimised for conventional
      chest radiography was evaluated by four thoracic radiologists. MATERIALS AND
      METHODS: The twin screen-film cassette system produces two film images, the front
      film optimised for the mediastinal region of the chest, the rear for the lung
      region. Image degradation on either screen-film system due to internal photon
      scatter has been virtually eliminated due to the use of a dividing filter. Fifty
      patients were included in a trial that resulted in a set of chest images for each
      patient, taken on the same inspiration, by both the twin screen-film cassette and
      the conventional system. The resultant fifty sets of images were evaluated by
      four chest radiologists who scored 12 radiographic features of the chest and
      patient pathologies present, using a paired difference technique. RESULTS: The
      image quality of the twin screen-film cassette system was judged to be
      significantly superior to the conventional screen-film system in nine of the 12
      radiographic features scored (P < 0.003). In the three other regions and for the
      patient pathologies, no significant conclusions were drawn. CONCLUSION: The new
      twin screen-film system showed improved visualisation of radiographic features,
      particularly in the mediastinal and retrocardiac lung regions. This new system
      shows promise in both standard and portable clinical applications.

PMID- 9587770
TI  - CT features of retroperitoneal neurilemmoma.
AB  - PURPOSE: The aim of this study was to characterize the CT features of
      retroperitoneal neurilemmoma. METHODS: The CT findings were reviewed in seven
      patients with retroperitoneal neurilemmoma. RESULTS: All of the tumours were well
      demarcated round or oval masses. In five cases, heterogeneous contrast
      enhancement was noted after contrast medium administration. Areas of minimal
      enhancement reflected diffuse edema in one tumour. Areas without definite
      enhancement represented prominent cyst formation in three tumours. There were
      three cases with tumour calcification (two with punctate calcification and one
      with mottled calcification). CONCLUSION: CT findings may suggest the diagnosis of
      retroperitoneal neurilemmoma preoperatively.

PMID- 9587771
TI  - Primary cardiac leiomyosarcoma: imaging with 2-D echocardiography, electron beam
      CT and 1.5-Tesla MR.

PMID- 9587772
TI  - Ultrasound and CT findings of a cecal lymphangioma presenting with
      intussusception.
AB  - A rare case of cecal lymphangioma which presented as intussusception was
      reported. The patient was a 28-year-old female who suffered from vomiting,
      abdominal pain and mass for 6 days. Ultrasonography revealed a multilocular cyst
      that measured 7 cm in maximal diameter, and an adjacent target-like mass with
      concentric layering in the right abdomen. Computed tomography confirmed the
      sonographic findings with fatty component in the target-like mass.
      Intussusception in adults is a diagnostic challenge to a physician due to its
      vague and nonspecific presentations. Laparatomy is indicated because of
      underlying pathology in a vast majority of cases. Diagnosis can be established by
      the characteristic findings mentioned above.

PMID- 9587773
TI  - [Adjuvant treatment of schizophrenic illness with carbamazepine].
AB  - Very few controlled clinical trials have been assessing the interaction of
      antipsychotics and antiepileptics. However, schizophrenic patients frequently
      receive a combination therapy consisting of haloperidol and carbamazepine. The
      data for this treatment strategy are contradictory and may depend on the initial
      plasma concentration of the antipsychotic. There is convincing evidence that
      after addition of carbamazepine the plasma concentration of neuroleptics drops
      due to hepatic enzyme induction. In this study, we treated 18 schizophrenic
      patients either with haloperidol alone or in combination with carbamazepine. The
      use of carbamazepine was associated with a dramatic fall in haloperidol plasma
      levels and a worse clinical outcome compared to the monotherapy group. These
      results, together with a review of the literature, lead us to the conclusion that
      there are no obvious advantages of carbamazepine co-medication in schizophrenia
      compared to an optimized neuroleptic monotherapy.

PMID- 9587774
TI  - [Suicide in the Bible from the current psychodynamic viewpoint. "There Saul took
      a sword and fell upon it"].
AB  - After a short introduction to psychoanalytical interpretation of literature in
      general and in the Bible, the stories of Samson and King Saul are examined on the
      basis of modern psychoanalytical aspects of suicidology (narcissistic theory,
      object relation theory, self psychology). Samson's beginning is hallmarked by the
      uncertainty of his parents, their megalomanic fantasies which are projected on
      the child. His relationships are characterized by violent emotions, intensive
      conflicts on intimacy and distance and also raging anger at insults and
      privation. In his suicide he fuses himself with the highly ambivalent primary
      object and destroys it at the same time he destroys himself. People with
      narcissistic personality are considered to be extremely suicidal especially in
      combination with the destructive potency of narcissistic anger.

PMID- 9587775
TI  - [Transitory global amnesia--psychogenic origin of organic disease?
      Psychopathologic basis and pathogenetic considerations].
AB  - Transient global amnesia (TGA) is an acute amnestic syndrome without neurological
      symptoms and remitting spontaneously. Though cerebral ischemia, epilepsy, and
      migraine have been implicated in some cases, non of these factors could be proven
      responsible for most, and etiology remains unclear. Of special interest is the
      induction of TGA by psychological and emotional stress in about 14-29% of all
      cases, which is illustrated by the clinical example of a 72-year-old women who
      suffered an attack of TGA after discovering a burglary in her home.
      Psychopathological and pathogenetic aspects are discussed in the context of
      recent neurobiological memory research. This suggests that TGA involves transient
      dysfunction of a specific memory subsystem associated with hippocampal
      structures. Neural network modelling explains the syndrome of TGA on a
      pathogenetic basis allowing for heterogeneous etiology and even for psychogenic
      release. Thus TGA serves as a model for pathogenetic explanation in the neuro
      psychiatric borderland.

PMID- 9587776
TI  - [Standards for treatment and expert opinion on transsexuals. The German Society
      for Sexual Research, The Academy of Sexual medicine and the Society for Sexual
      Science].
AB  - Over the last two-and-a-half years a committee of experts, consisting of members
      of the three leading German sexology associations, developed guidelines for
      treating and assessing transsexuals. Their purpose is to improve the care for
      patients with sex identity disorders and to ensure that such care is of uniform
      quality to avoid erroneous decisions to the disadvantage of those affected. The
      guidelines are set out in full.

PMID- 9587777
TI  - [Schizophrenic prelingual deaf and hearing patients. A comparison of premorbid
      and current data after several years of progression].
AB  - Prelingually deaf persons belonging to a linguistic and cultural minority have to
      cope with a particular sociocultural situation. The present study endeavours to
      analyse possible effects of this situation in the course and outcome of
      schizophrenia. Two samples, one comprising 27 prelingually deaf and one 27
      hearing patients, all with schizophrenic psychoses, were parallelised on the
      basis of gender, age, duration of illness and number of previous
      hospitalisations. Data were then collected on the premorbid and current social
      situation and on the psychopathometric outcome after an (on the average) ten-year
      course. The prelingually deaf patients were much more profoundly impaired with
      regard to the rating of their residual symptoms and their social situation than
      those of the hearing control group. Only with respect to vocational
      rehabilitation did the prelingually deaf patients record a slightly more
      favourable situation than the hearing patients, as a greater proportion of them
      had regular employment, in most cases in workshops for the disabled.

PMID- 9587778
TI  - [Psychophysiology, signs and symptoms of disease the course of normal pressure
      hydrocephalus].
AB  - Between May 1982 until January 1997 we investigated 200 patients suspected for
      normal pressure hydrocephalus (NPH) by performing an intrathecal infusion test.
      According to our experiences gait ataxia is the leading symptom of NPH. Regarding
      dementia we could not find a significant difference compared to cerebral atrophy.
      Bladder incontinence can be characterised as a symptom of late-stage NPH. The
      complete Hakim trias should not be overestimated in differential diagnostic
      considerations. Graduation of NPH and cerebral atrophy after the results of the
      infusion test in an early and late stage enables prognostic evaluation of the
      course of disease. Patients with NPH in an early stage report in the follow-up on
      an improvement of their symptoms after shunt operation (65 percent of patients),
      whereas 50 percent of the patients with late stage NPH were improved. The
      computer-aided infusion test allows secure differentiation between patients with
      NPH and those with cerebral atrophy.

PMID- 9587779
TI  - Cytotoxicity of xenobiotics and expression of glutathione-S-transferases in
      immortalised rat hepatocyte cell lines.
AB  - 1. Immortalised rat hepatocyte cell lines are more sensitive to the cytotoxicity
      of 1-chloro-2,4-dinitrobenzene and ethacrynic acid than primary cultures of
      hepatocytes. 2. Class alpha glutathione S-transferases are not expressed in
      immortalised hepatocyte cell lines. Class pi glutathione S-transferase expression
      is elevated in the immortalised cell lines compared with freshly isolated
      hepatocytes, but it is not as high as in the HTC rat hepatoma cell line. 3.
      Immortalised hepatocyte cell lines may provide a sensitive model system for
      detecting cytotoxicity associated with xenobiotics which are detoxified by
      glutathione S-transferases.

PMID- 9587780
TI  - Antimony leaching from cot mattresses and sudden infant death syndrome (SIDS).
AB  - 1. Polyvinyl chloride (PVC) cot mattress covers from SIDS cases were investigated
      as potential sources of soluble (potentially ingestable) antimony in the cot
      environment. 2. Body fluids (urine, saliva) and proprietary domestic
      detergents/sterilizing fluids markedly enhanced leaching of antimony from PVC.
      Release of antimony was also enhanced at both low and high pH and by elevated
      temperature. The extent of antimony leaching did not correlate well with PVC
      content of this element. 3. These data do not support the assumption that
      postmortem analysis of antimony content proves exposure to gaseous antimony
      trihydride from mattress PVC. 4. Ingestion of antimony released from PVC could
      account for the high variability associated with reported detectable levels of
      antimony in liver from both SIDS and other infants. It could also explain
      suspected additional postnatal exposure to this element, which gives rise to
      elevated levels of Sb in the hair of some healthy infants.

PMID- 9587781
TI  - Lack of inhibition of human plasma cholinesterase and red cell
      acetylcholinesterase by antimony compounds including stibine.
AB  - 1. The toxic gas hypothesis proposes exposure to stibine (antimony trihydride)
      generated from microbial contamination of cot mattress materials as a possible
      cause of unexplained death in infancy (SIDS) as a consequence of cholinesterase
      inhibition. We have measured the direct effects of antimony compounds including
      stibine on the activity of plasma cholinesterase, red blood cell
      acetylcholinesterase (AChE) and mouse neuronal AChE in vitro. 2. Colorimetric
      assays for the different esterases with potassium antimonyl tartrate or antimony
      trichloride at concentrations up to 10(-3) M in the presence of substrate
      concentrations sufficient to produce 80% of the maximum reaction rate produced no
      inhibition of enzyme activity. Exposure of enzyme preparations to stibine gas at
      concentrations sufficient to cause denaturation of red cell haemogloblin caused
      no measurable inhibition of esterase activity. 3. We conclude that stibine gas or
      soluble antimony compounds are not capable of inhibiting cholinesterase activity
      at toxicologically relevant concentrations.

PMID- 9587782
TI  - The influence of ethanol on long-term effects of dibutyltin dichloride (DBTC) in
      pancreas and liver of rats.
AB  - The present study was done to determine the additional influence of daily ethanol
      intake (15% in drinking water ad libitum) on long-term toxic effects of a single
      administration of dibutyltin dichloride (DBTC, 8 mg/kg b.w. i.v.) in pancreas and
      liver of rats. Pathohistological changes in pancreas, bile duct and liver as well
      as pathobiochemical parameters of pancreatitis (amylase and lipase activity),
      liver lesions (alkaline phosphatase activity and bilirubin) and fibrosis
      (hydroxyproline and hyaluronic acid) were measured 1 day and 1 to 24 weeks after
      DBTC- and DBTC/ethanol administration. DBTC alone induced in rats an acute
      interstitial pancreatitis as well as acute bile duct and liver lesions in the
      early experimental phase. Later on, the acute inflammatory processes in pancreas
      and liver took a chronic course resulting in pancreatic fibrosis and liver
      cirrhosis. Ethanol increased the toxic effects of DBTC on pancreas and liver
      during the acute and chronic course. In the acute phase lasting 1 day to 2 weeks,
      ethanol enhanced the DBTC toxicity on acinar cell and bilio-pancreatic duct
      epithelium as well as the formation of obstructive ductal plugs by necrotic cell
      debris. The obstruction and cholestasis in the DBTC/ethanol-group were
      significantly stronger as in the DBTC-group. The significant increase of
      hydroxyproline in urine and hyaluronic acid in serum of the DBTC/ethanol treated
      rats after 12 to 24 weeks was connected with a more severe chronic inflammatory
      fibrosis in pancreas and liver in comparison to the DBTC-treated group.

PMID- 9587783
TI  - Reproductive toxicity and tissue concentrations of 3,3',4,4'-tetrachlorobiphenyl
      (PCB 77) in male adult rats.
AB  - 1 The aim of this study was to ascertain the reproductive effects of PCB 77 on
      adult male rats and to determine its concentration in the liver and testis. Adult
      male rats (n = 15/group) were treated subcutaneously with a single dose of 18
      mg/kg bw (PC18) or with 60 mg/kg bw (PC60). The substance was dissolved in a 10
      ml volume of peanut oil/kg. Control rats received the same volume of the vehicle.
      The reproductive effects as well as the concentration of PCB 77 in the liver and
      testis were investigated 1, 4 and 8 weeks after treatment. 2 In both groups, the
      daily sperm production (DSP; x10(6)) remained permanently reduced in the PC18 as
      well as in the PC60 groups throughout the entire investigation period (DSP week
      8: control: 31 +/- 7; PC18: 22 +/- 5; PC60: 20 +/- 7). The sperm number (x10(6))
      per cauda epididymis was affected only at the 1st and 4th week after treatment
      (control week 1: 211 +/- 67; PC18 week 1: 135 +/- 62; PC60 week 1: 142 +/- 49).
      Moreover, a significant increase in the percentage of abnormal sperm was observed
      4 weeks following treatment in the PC18 and PC60 groups and 8 weeks after
      treatment in the PC60 group. Abnormal tails were the most frequent changes
      observed. 3 The relative testicular and prostata weights (g) were slightly
      increased in the PC60 group at the 1st and 4th week following treatment (testis
      weight: control/I: 0.46 +/- 0.02; PC60/I: 0.51 +/- 0.03). 4 The serum
      testosterone concentrations and effects on testis morphology were not reported. 5
      The maximum concentration of PCB 77 was detected in the liver and testis 1 week
      after treatment. The concentration declined 4 weeks after treatment in both
      organs, but still a significant amount of PCB 77 was detectable in the liver as
      well as in the testis 8 weeks after treatment. 6 The results demonstrate that PCB
      77 affects sperm variables when applied to adult rats and that the elimination of
      PCB 77 in the testis parallels that of the liver.

PMID- 9587784
TI  - Differential recovery of acetylcholinesterase in guinea pig muscle and brain
      regions after soman treatment.
AB  - 1. In brain areas of untreated guinea-pigs the highest activity of
      acetylcholinesterase was seen in the striatum and cerebellum, followed by the
      midbrain, medulla-pons and cortex, and the lowest in the hippocampus. The
      activity in diaphragm was seven-fold lower than in the hippocampus. 2. At 1 h
      after soman (27 micrograms/kg) administration the activity of the enzyme was
      dramatically reduced in all tissues studied. In muscle the three major molecular
      forms (A12, G4 and G1) showed a similar degree of inhibition and a similar rate
      of recovery and the activity had returned to normal by 7 days. 3. In the brain
      soman inhibited the G4 form more than the G1 form. The hippocampus, cortex and
      midbrain showed the greatest reductions in enzyme activity. At 7 days the
      activity in the cortex, medulla pons and striatum had recovered but in the
      hippocampus, midbrain and cerebellum it was still inhibited. 4. Thus the effects
      of soman administration varied in severity and time course in the different
      tissues studied. However the enzyme activity was still reduced in all tissues at
      24 h when the overt signs of poisoning had disappeared.

PMID- 9587785
TI  - alpha-Tocopherol (vitamin-E) ameliorates ferric nitrilotriacetate (Fe-NTA)
      dependent renal proliferative response and toxicity: diminution of oxidative
      stress.
AB  - Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this
      communication, we show the modulatory effect of DL-alpha-tocopherol (Vitamin-E)
      on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, toxicity and
      hyperproliferative response in rats. Fe-NTA-treatment enhances the susceptibility
      of renal microsomal membrane for iron-ascorbate-induced lipid peroxidation and
      hydrogen peroxide generation which are accompanied by a decrease in the
      activities of renal antioxidant enzymes, catalase, glutathione peroxidase,
      glutathione reductase and glutathione-S-transferase and depletion in the level of
      renal glutathione. Parallel to these changes, a sharp increase in blood urea
      nitrogen and serum creatinine has been observed. In addition, Fe-NTA-treatment
      also enhances renal ornithine decarboxylase activity (ODC) and increases
      [3H]thymidine incorporation in renal DNA. Prophylactic treatment of animals with
      Vit.E daily for 1 week prior to the administration of Fe-NTA resulted in the
      diminution of Fe-NTA-mediated damage. Enhanced susceptibility of renal microsomal
      membrane for lipid peroxidation induced by iron-ascorbate and hydrogen peroxide
      generation were significantly reduced (P < 0.05). In addition, the depleted level
      of glutathione and inhibited activities of antioxidant enzymes recovered to
      significant levels (P < 0.05). Similarly, the enhanced blood urea nitrogen and
      serum creatinine levels which are indicative of renal injury showed a reduction
      of about 50% at a higher dose of Vit.E. The pretreatment of rats with Vit.E
      reduced the Fe-NTA-mediated induction in ODC activity and enhancement in
      [3H]thymidine incorporation in DNA. The protective effect of Vit.E was dose
      dependent. In summary, our data suggest that Vit.E is an effective
      chemopreventive agent in kidney and may suppress Fe-NTA-induced renal toxicity.

PMID- 9587786
TI  - Immunoglobulin levels in workers exposed to hexachlorobenzene.
AB  - The serum immunoglobulin (IgG, IgM and IgA) concentrations of 52 chlorinated
      exposed workers were examined and compared with those of non-exposed, age- and
      sex-matched individuals. At the time of testing, the exposed population had mean
      hexachlorobenzene (HCB) blood levels of 3.84 micrograms/dl with a range of 0.1 to
      16 micrograms/dl. Increased IgG and IgM levels were found in the HCB-exposed
      workers (P < 0.05 and P < 0.01, respectively). Hepatic function was evaluated by
      serum aspartate (AST) and alanine aminotransferase (ALT) activities, as well as
      by bilirubin levels. IgM concentrations were positively correlated with three of
      the studied parameters, namely, length of exposure (r = 0.367) and the activities
      of both AST (r = 0.367) and ALT (r = 0.507).

PMID- 9587787
TI  - Sites of lead and nickel accumulation in the placental tissue.
AB  - 1. There is a variety of quantitative analytical data regarding the total
      concentrations of heavy metals in human placentae. However, little is known about
      sites of metal accumulation in the placental tissue structural zones in relation
      to the environment. In this study, the lead and the nickel particulate deposits
      in the placental chorionic plate, the chorionic villous tree and the basal plate,
      using tissue histochemical reactions for lead and nickel, have been estimated.
      The degree of metal contamination of placentae was assessed according to an
      arbitrary scale. Both metals have shown a common mode of accumulation in the
      placental tissue structural zones. Among the observed contaminated structures in
      the placental tissue, the syncytiotrophoblast was the most frequent site for lead
      and nickel particulate deposits. 2. The frequency distribution of both metals
      within the mentioned placental zones, using four metal contamination degrees, was
      determined. A heavily contaminated zone was found to be the chorionic villous
      tree, especially in samples from the industrial region. 3. A comparison between
      two Slovak regions (an industrial and a rural one) using statistical tests was
      performed. The frequency of samples without any lead occurrence in the chorionic
      villous tree was found to be 10% in the industrial region, and 16% in the rural
      region. Regarding the nickel deposits, the frequency of non-contaminated samples
      in the industrial region was 2%, whereas in the rural region 6%. A relationship
      between traffic related pollution and human placenta contamination was found in
      both investigated regions.

PMID- 9587788
TI  - Acute paraquat poisoning: increased toxicity in one case with high alcohol
      intake.
AB  - Human paraquat poisoning from accidental or intentional ingestion is very often
      fatal. According to the amount of paraquat involved, death can occur within hours
      or weeks following ingestion. The inefficacy of the various treatments undertaken
      have led to determine prognostic factors based upon the evolution of plasma and
      urine paraquat concentrations or of usual biochemical parameters. We report one
      case of acute poisoning which, although the ingested dose of paraquat was not
      massive (< 50 mg/kg-1) and the severity indices were in favour of a delayed fatal
      outcome, has ended in an early death. The high blood alcohol level of the patient
      (3.34 g l-1) seems to be the main cause of the precocity of this death (86th
      hour).

PMID- 9587789
TI  - Mechanism of action of honey bee (Apis mellifera L.) venom on different types of
      muscles.
AB  - 1. The effect of crude honeybee (Apis mellifera) venom on the skeletal, smooth as
      well as cardiac muscles were studied in this investigation. 2. Perfusion of
      gastrocnemius-sciatic nerve preparation of frogs with 1 microgram/ml venom
      solution has weakened the mechanical contraction of the muscle without recovery.
      Blocking of nicotinic receptors with 3 micrograms/ml flaxedil before bee venom
      application sustained normal contraction of gastrocnemius muscle. 3. The
      electrical activity of duodenum rabbits was recorded before and after the
      application of 1 microgram/ml venom solution. The venom has depressed the
      amplitude of the muscle contraction after 15 min pretreatment with atropine
      nearly abolished the depressor effect of the venom on smooth muscle. 4. In
      concentrations from 0.5-2 micrograms/ml, bee venom caused decrease of heart rate
      of isolated perfused toad heart. This bradycardia was accompanied by elongation
      in the P-R interval. A gradual and progressive increase in the R-wave amplitude
      reflected a positive inotropism of the venom. Application of 5 micrograms/ml
      verapamil, a calcium channels blocking agent, abolished the noticed effect of the
      venom. 5. Marked electrocardiographic changes were produced within minutes of the
      venom application on the isolated perfused hearts, like marked injury current
      (elevation or depression of the S-T segment), atrioventricular conduction
      disturbances and sinus arrhythmias. Atropine and nicotine could decrease the
      toxic effect of the venom on the myocardium. 6. Results of the present work lead
      to the suggestion that bee venom is mediated through the peripheral cholinergic
      neurotransmitter system. General neurotoxicity of an inhibitory nature involving
      the autonomic as well as neuromuscular system are established as a result of the
      venom, meanwhile a direct effect on the myocardium membrane stabilization has
      been suggested.

PMID- 9587790
TI  - Commentary on 'an unusual poisoning with the unusual pesticide amitraz' with
      respect to the pharmacology of amitraz.

PMID- 9587791
TI  - Stability of trihexyphenidyl in stored blood and urine specimens.
AB  - Trihexyphenidyl (THP) is an anticholinergic agent with forensic toxicological
      interest. The stability of THP was studied in postmortem blood and urine samples
      at a concentration of 0.25 microgram/ml under different storage temperatures.
      After solid phase extraction (SFE), THP was measured by gas chromatography. On
      day zero and at intervals over a 6 months period, there was no significant loss
      of THP at the storage temperatures -20 degrees C and 4 degrees C in the spiked
      and authentic samples. Blood and urine samples stored at 25 degrees C showed a
      maximum recovery loss (about 14%) of THP after 3 months of storage. This loss was
      considered a significant change and corresponded to a P value < 0.046. The study
      demonstrates that the analysis of blood and urine samples containing THP would
      produce consistent results when they are stored for 6 months at -20 or 4 degrees
      C and for 3 months at 25 degrees C.

PMID- 9587792
TI  - Ketoacidosis and lactic acidosis--frequent causes of death in chronic alcoholics?
AB  - In clinical medicine, severe keto- or lactic acidosis associated with vomiting,
      nausea, abdominal pain, tachycardia or pathological respiration, has been
      described in chronic alcoholics. This study reports on fatalities of chronic
      alcoholics where the cause of death could not be determined by thorough autopsy,
      histology and toxicology including determination of alcohol concentration. In a
      first series, acetone was determined in the blood of such chronic alcoholics (n =
      24), diabetics with metabolic decompensation (n = 7), cases of hypothermia (n =
      7) and controls (n = 218). Among the 24 chronic alcoholics where the cause of
      death was unknown, 9 cases showed very high levels of acetone (74-400 mg/l).
      These comprised 6 cases without additional findings and 3 cases where a second
      patho-mechanism such as intoxication possibly contributed to the cause of death.
      In a second series, the sum values according to Traub (lactate/glucose) were
      determined in cerebrospinal liquor of chronic alcoholics with undetermined cause
      of death (n = 45), diabetics (n = 6) and controls (n = 39). Among the 45
      alcoholics, 17 cases showed very high sum values (294-594 mg/dl) including 8
      cases where non-lethal intoxications may have contributed to the final outcome.
      Other causes of a ketoacidosis or lactic acidosis (e.g. diabetes) were excluded
      in both groups of alcoholics. Consequently, ketoacidosis and lactic acidosis can
      be the cause of death of chronic alcoholics in a considerable number of cases
      where no pathomorphological or toxicological changes are present. A scheme for
      medical and laboratory examination is described.

PMID- 9587793
TI  - Falling asleep whilst driving: are drivers aware of prior sleepiness?
AB  - Falling asleep at the wheel is a common cause of road accidents, but little is
      known about the extent to which drivers are aware of their sleepiness prior to
      such accidents. It is an area with medico-legal implications. To simulate this
      situation 28 healthy young adult experienced drivers, sleep restricted the night
      before drove for 2 h in the afternoon in an interactive real-car simulator
      incorporating a dull and monotonous roadway. Lane drifting, typifying sleepy
      driving, was subdivided into minor and major incidents, where the latter was
      indicative of actually falling asleep. A distinction was made between the
      subjective perceptions of sleepiness and the likelihood of falling asleep which
      drivers reported separately. Increasing sleepiness was closely associated with an
      increase in the number of incidents. Major incidents were preceded by self
      awareness of sleepiness well beforehand and typically, subjects reached the stage
      of fighting sleep when these incidents happened. Whilst the perceived likelihood
      of falling asleep was highly correlated with increasing sleepiness, some subjects
      failed to appreciate that extreme sleepiness is accompanied by a high likelihood
      of falling asleep. It was not possible for our subjects to fall asleep at the
      wheel and have an "accident" without experiencing a sustained period of
      increasing sleepiness, of which they were quite aware. There is a need to educate
      at least some drivers that extreme sleepiness is very likely to lead to falling
      asleep and a high accident risk.

PMID- 9587794
TI  - Population data for 101 Austrian Caucasian mitochondrial DNA d-loop sequences:
      application of mtDNA sequence analysis to a forensic case.
AB  - The sequence of the two hypervariable segments of the mitochondrial DNA (mtDNA)
      control region was generated for 101 random Austrian Caucasians. A total of 86
      different mtDNA sequences was observed, where 11 sequences were shared by more
      than 1 individual, 7 sequences were shared by 2 individuals and 4 sequences were
      shared by 3 individuals. One of the four most common mtDNA sequences in Austrians
      is also the most common sequence in both U.S. and British Caucasians, found in
      approximately 3.0% of Austrians, 4.0% of British, and 3.9% of U.S. Caucasians. Of
      the remaining three common Austrian sequences, one was not observed in either
      U.S. or British Caucasians. However, three British Caucasians exhibited a similar
      sequence type. Therefore, this particular cluster of sequence polymorphisms may
      represent a common "European" mtDNA sequence type. In general, Austrian
      Caucasians show little deviation from other Caucasian databases of European
      descent. Finally, mtDNA sequence analysis was applied to a forensic case, where
      hairs found at a crime scene matched the control hairs from the suspect.

PMID- 9587795
TI  - Differential typology and prognosis for dissexual behavior--a follow-up study of
      previously expert-appraised child molesters.
AB  - In terms of identifying socially-dysfunctional forms of sexuality--regardless of
      the legal valuation--dissexuality is defined as "an expression of social failure
      in sexual behavior." This failure was the subject of a longitudinal analysis of
      186 expert-appraised pedophile sexual delinquents at the University of Kiel from
      1945 through 1981. Of the child molesters 121 were followed up between September
      1990 and September 1992 and 100 were personally contacted. The goal was to
      empirically develop prognosis criteria, given knowledge of the former
      delinquents' social development as well as sexual/dissexual practices, which
      could be of both forensic and interdisciplinary use. Among the bi- and
      homosexually-orientated pedophiles, the number of offenders for which the act is
      one of "compensation" was half of the initial collective. In contrast, this
      number was three-quarters for the heterosexually-orientated perpetrators.
      Correspondingly, the other half of the bi- and homosexually-orientated pedophiles
      were either exclusive-type or non-exclusive-type pedophiles (the so-called "true"
      pedophiles). Among the heterosexually-orientated offenders, the number was only
      one-quarter. According to the empirical data, we may expect a biographically
      continuing potential of dissexual behavior for only the exclusive and the non
      exclusive type of pedophilia. Most of the relapsed dissexual activities showed up
      a long time after the expert's report. This is true for both the heterosexually-
      and the bi- and homosexually orientated groups. The present evaluation of the
      results allows assignment of behavior for certain delinquent typologies
      restricted to life phases or lifelong dissexual behavior.

PMID- 9587796
TI  - Increased forensic efficiency of a STR-based Y-specific haplotype by addition of
      the highly polymorphic DYS385 locus.
AB  - The polymorphic short tandem repeat (STR) locus DYS385 mapping to the male
      specific region of human Y chromosome, was used to reinvestigate 125 unrelated
      Italian males, from our data archive, who had been previously typed for 7
      different Y-specific STRs (DYS19, DYS389 I and II, DYS390, DYS391, DYS392,
      DYS393), defining a haplotype now widely adopted in the forensic context. The aim
      of this study was to improve the information value of the original haplotype in
      view of its application to issues of personal identification and parental
      analysis. DYS385 proved to be highly polymorphic (94.5% gene diversity) and the
      overall individualization capacity of the 8-loci haplotype was raised to 93.6%,
      with 117 unique assets out of 125 tested samples.

PMID- 9587797
TI  - Honey with Psilocybe mushrooms: a revival of a very old preparation on the drug
      market?
AB  - In 1996 samples of suspicious honey preparations were confiscated at the Dutch
      German border. The labels on the 50 ml jars indicated that the honey contained
      Stropharia cubensis (better known as Psilocybe cubensis). The jars were filled
      with honey with a ca. 1 cm layer of fine particles on the top. The particles were
      collected and subjected to microscopic and chemical analysis. By microscopy
      mushroom tissue (plectenchym) and spores typical for the genus Psilocybe were
      identified in all samples. The HPLC analysis with atmospheric pressure mass
      spectrometry and diode array detection revealed psilocine but psilocybine was not
      found. The quantitative analysis was very difficult due to the matrix problems. A
      search showed that the honey with Psilocybe can be purchased in Dutch coffee
      shops without any limitations although psilocine and psilocybine belong to listed
      substances according to Dutch law.

PMID- 9587798
TI  - A fatal case of suicidal pentoxifylline intoxication.
AB  - Pentoxifylline is a xanthine derivative used in the treatment of peripheral
      vascular disease. It is considered to be a safe drug and to the best of our
      knowledge there are no reports in the medical literature of cases of fatal
      poisoning. There is only one previous report of a young woman who tried to commit
      suicide by taking a large amount of the drug but recovered. We report the case of
      a 54-year-old man who took a massive dose of pentoxifylline and died after 24 h
      from refractory shock. The blood levels of pentoxifylline were as high as 32.5
      micrograms/ml where the average therapeutic level is 1.3 micrograms/ml.

PMID- 9587799
TI  - Mechanism of fatal air embolism after gastrointestinal endoscopy.
AB  - Although venous air embolism is a known complication in medical practice in
      general, only a single case of upper gastrointestinal endoscopy complicated by
      venous air embolism with consecutive acute cardiovascular failure has so far been
      described in literature. Here we show that gastroscopy may be accompanied by
      massive, i.e. fatal venous air embolism. If a vessel in the gastrointestinal
      tract is exposed but does not collapse (in the case of a gastric ulcer, for
      example) air insufflated under pressure by the gastroscope may lead to a fatal
      air embolism. Our tests using a commercial gastroscope revealed that an
      overpressure of up to 43 kPa (kiloPascals) is reached without the rinsing
      function while an overpressure of up to 45 kPa is measured if the rinsing
      function is operated simultaneously. The maximum flow rates without resistance
      were 100 ml/min for rinsing liquid (purified water) and 2000 ml/min for air. Our
      results suggest that air insufflation by the gastroscope may result in a critical
      air embolism within very few seconds on condition that a connection with the
      vascular system exists. However, this complication is extremely rarely
      encountered. We propose that CO2 should be administered in place of air or
      alternatively the maximum pressure should be considerably reduced to avoid a
      fatal outcome in routinely performed gastroscopical examinations.

PMID- 9587800
TI  - A new technique for the postmortem detection of tooth-coloured dental
      restorations.
AB  - Identification of unknown bodies is mainly made by dental examination and
      comparison with accurate dental records. Therefore it is necessary to examine the
      jaws carefully and to locate every tooth-coloured dental restoration. Overlooking
      dental fillings can make positive identification impossible. The technique
      described prepares the natural dental hard tissue by etching with 37% phosphoric
      acid. In the next step an indicator colours the roughened dental tissue but not
      the polished restoration material. In this way all 15 tested dental restoration
      materials could be detected with high sensitivity.

PMID- 9587801
TI  - Population genetic data of the STR HumD3S1358 in two regions of Germany.
AB  - This report gives the results of two population studies on HumD3S1358 from a
      northern and a southern region of Germany. The numbers of unrelated individuals
      were 326 and 666, respectively and seven main alleles, three rare allelic
      variants and 29 different genotypes were encountered. No significant statistical
      differences were seen between the northern and southern populations. The
      HumD3S1358 allele distributions were in agreement with Hardy-Weinberg
      expectations and two mutations were found in 780 meiotic events.

PMID- 9587802
TI  - Basque Country autochthonous population data on 7 short tandem repeat loci.
AB  - Blood samples from 202-208 unrelated Basque Country autochthonous individuals
      were amplified, typed and their allele frequencies were determined. Results
      demonstrate the assumption of independence within and between the loci analyzed.
      Therefore, a Basque population database can be used in identity testing to
      estimate the frequency of a multiple PCR-based locus DNA profile.

PMID- 9587803
TI  - Stability of morphine and buprenorphine in whole blood.
AB  - Delays between time of sampling and time of toxicological analysis are common,
      therefore the length of time that postmortem blood can be stored at various
      temperatures (e.g. 4 degrees, 25 degrees, -20 degrees C) was evaluated for the
      effect on the stability of morphine and buprenorphine from day one up to one
      year. Solid phase extraction and GC-MS were used for the isolation and
      quantification of the drugs. Morphine and buprenorphine were found to be very
      stable for up to 6 months under these storage conditions, where at least 85% and
      77% of morphine and buprenorphine respectively, were recovered. The study showed
      that a reasonable amount of the drugs (not less than 70%) was still detectable
      after one year of storage regardless of the temperature when blood samples were
      stored in silanized glass vessels.

PMID- 9587804
TI  - Quality control, condensed analysis and ethics.

PMID- 9587805
TI  - Thick- and thin-skinned organisations and enactment in borderline and
      narcissistic disorders.
AB  - In this paper the author argues that enactment is any mutual action within the
      patient/analyst relationship that arises in the context of difficulties in
      countertransference work. Such enactment is common during the treatment of
      borderline and narcissistic disorders. In order to delineate different forms of
      enactment, which in his view may be either to the detriment or to the benefit of
      the analytic process, the author describes a patient who was identified primarily
      with a sadistic mother and who threatened the analyst with a knife during
      treatment. Three levels of enactment involving countertransference responses are
      described of which two, namely a collusive countertransference and a defensive
      countertransference, were detrimental to the analytic process. The third level of
      enactment was beneficial but only because the intervention by the analyst was
      independent of the analytic process and yet in response to it. The author uses
      Rosenfeld's distinction between thin-skinned and thick-skinned narcissists to
      illustrate how enactment is most likely when a patient moves between thick
      skinned and thin-skinned narcissistic positions. Nevertheless the move between
      thin and thick-skinned positions presents an opportunity for effective
      interpretation, allowing progress in treatment.

PMID- 9587806
TI  - Disavowal of reality as an act of filial piety.
AB  - The author argues that often the hidden power of disavowal of reality gradually
      makes itself felt in a treatment. The psychoanalytic process then seems to have
      been brought to a halt by something that defies meaning and continually eludes
      any genuine subjectivisation by the patient. In the famous case of the Wolf Man
      (1918), Freud speaks of a rejection of reality, which he clearly distinguishes
      from repression, in that the rejected representation has not in any way been
      erased from consciousness; rather, its meaning remains as if in suspension, no
      longer open to judgement. Certain key moments in the treatment of a borderline
      case help to illustrate the necessity for the analyst to grasp the peculiar
      nature of his own involvement. He may have been induced to assume a parental
      attitude reproducing a 'community of disavowal' that belongs to the patient's
      unrecognised history. By adopting an interpretive formulation acknowledging his
      own participation in the disavowal--which the parents must have been unable to do
      -the analyst can then allow the patient to get out from under it. These
      considerations allow us to shed light on two possible theoretical difficulties
      regarding, firstly, the difference between negation and disavowal of reality and,
      secondly, the way that the disavowal tends to hamper the very process of
      symbolisation necessary for the deployment of fantasy.

PMID- 9587807
TI  - Electra versus Oedipus. Femininity reconsidered.
AB  - The author discusses the arguments in favour of an Electra rather than an Oedipus
      complex to describe the vicissitudes of female development and explores the value
      of using a different paradigm. She concludes that girls do not have to change
      their primary object to become female. Pathological forms of the normal
      ambivalent attachment to the mother are vehement rejection, as with Electra, or
      the opposite, a close symbiotic bond. Both outcomes testify to the centrality of
      the maternal love object for the girl, and either can lead to masochistic
      resolutions of the mother-daughter bond. The girl must steer between the Scylla
      of a symbiotic illusion vis-a-vis her maternal object and the Charybdis of hatred
      of it. The inner relationship with the maternal image can foster a woman's
      development, serve as a source of strength or be a well of pathology. Electra
      illustrates her preoccupation with her mother in a combination of latent approach
      and manifest avoidance. Women do turn to their male object of desire, not instead
      of, but in addition to their first love object, the mother. In healthy
      development, not the inner mother, but the childhood fantasy of the phallic
      mother is given up, allowing the difference between the parents to be recognised
      and genuine heterosexual desire established. Female heterosexuality will always
      be accompanied by a strong homosexual undercurrent.

PMID- 9587808
TI  - Persephone, the loss of virginity and the female oedipal complex.
AB  - The ancient myth of Persephone and her mother, Demeter, has been characterised as
      the most important myth about women and the mother-daughter relationship.
      Previous psychoanalytic interpretations of the myth have neglected its depiction
      of the girl's defence against a sense of agency over her sexuality. The authors
      present two examples of the use of this myth by an analytic patient and the
      writer, Edith Wharton. Both women consciously identified in childhood with the
      figure of Persephone. Aspects of the myth contributed to a central unconscious
      fantasy that illuminated their dynamics and sexual conflicts. The authors argue
      that the Persephone myth is essentially a portrayal of the oedipal dilemma that
      emphasises a conflict of loyalty towards father and mother, fear of loss of
      virginity and adult sexuality and a peaceful resolution. The female oedipal
      conflict is seen as different from that of the male, because the girl competes
      with the mother on whom she must depend as primary care-giver. Separation issues
      are encompassed within the female oedipal phase proper. It is proposed that the
      Persephone complex is better suited to representing women's issues than is the
      myth of Oedipus.

PMID- 9587809
TI  - Raymond de Saussure. First president of the European Psychoanalytical Federation.
AB  - The author reviews the life and career of the Swiss psychoanalyst Raymond de
      Saussure, who died in 1971. A member of an ancient Protestant family with a
      distinguished intellectual record in Geneva, Saussure studied medicine and
      psychiatry before turning to psychoanalysis after a fateful encounter with
      Sigmund Freud, with whom he subsequently maintained intermittent contacts. His
      subsequent efforts to establish psychoanalysis as a discipline in its own right
      separate from psychiatry, especially in the French-speaking countries, are
      described in detail. We learn of his important role in the promotion of
      psychoanalysis, the organisation of psychoanalytic training and the publication
      of psychoanalytic material, including his own substantial theoretical and
      clinical contributions. He is shown also to have had a wide range of other
      interests. Particular stress is laid on Saussure's Europeanism, as revealed in
      his familiarity with Germanic as well as French-language culture, his activities
      in France in addition to Switzerland, his role as an ambassador for European
      culture during his New York period, and, most importantly, his commitment to the
      formation of the European Psychoanalytical Federation, of which he was the first
      President. The author notes too that Saussure was a man of unfailing courtesy.

PMID- 9587810
TI  - The patient without a couch: an analysis of a patient with terminal cancer.
AB  - The author reports an unusual clinical experience arising from the tragic
      circumstances of a patient who contracted cancer at the beginning of the fifth
      year of an analytic process. Instead of interrupting the analysis, the analyst
      suggested having sessions by telephone, as this patient could no longer leave her
      home when the terminal phase of her illness set in. The experience proved
      beneficial for the patient and enriching for the analyst. The patient was able to
      contain, work through and integrate the meaning and consequences of her disease,
      make reparations to her objects, and accept death with dignity. The analyst also
      emerged from the experience strengthened and more aware of her own vulnerability
      and mortality. The author brings up three relevant questions based on a review of
      the literature. These questions are: should the patient be told of his/her
      diagnosis and to what purpose? Can there be a productive analysis with such
      patients? What psychic structure and emotional conditions allow a patient to bear
      the truth?

PMID- 9587811
TI  - A fe/male transsexual patient in psychoanalysis.
AB  - The author describes the analysis of a transsexual who had undergone a
      vaginoplasty as a young man and had since been living as a woman. The complexity
      of the psychic reality is epitomised by the analyst's difficulty in deciding
      whether to use masculine or feminine grammatical forms to refer to this patient.
      The author tells how she assumed the fantasy role of parents expecting a baby
      whose sex they did not yet know. She discusses at length her hesitation about
      accepting a transsexual patient into analysis and reports how she overcame her
      misgivings after analysing her own countertransference and consulting the
      literature. Noting that this borderline analysand resorted to both psychotic and
      neurotic mechanisms, the analyst decided to rely on the capacity for
      symbolisation and mental representation evinced in the latter. On the psychotic
      level, the delusional neo-reality of the appearance of a woman sought to replace
      the unbearable reality of being a man, whereas the neurotic part was aware that
      s/he could never really be a woman. The author observes that in this analysand
      sexualisation served to conceal a fundamental narcissistic fault. She also
      describes how she worked with her own madness to help the patient emerge from a
      situation of paradoxical fusion with the mother in madness.

PMID- 9587812
TI  - Religious experience and psychoanalysis: from man-as-god to man-with-god.
AB  - The author notes that the Freudian psychoanalytic view of religion has become a
      saturated concept that causes psychoanalysts to disregard the complexity of the
      religious experience. Issue is taken with the reductionism inherent in the
      conception of religion as mere illusion and the image of God as being derived
      solely from the oedipal father. After a presentation of the ideas of some later
      authors and discussion of the transition from the state of 'Man-as-God' to the
      relationship of 'Man-with-God' as portrayed in a film, two clinical vignettes are
      given to illustrate this process of humanisation. The author suggests that
      religious manifestations in patients should be seen not only in the light of
      their infantile determinants but also as the result of processes whereby new
      meaning is assigned to psychic facts. In his opinion, psychoanalysis should not
      seek solely to reduce religious beliefs to their roots in unconscious fantasies
      but should lead to a reorganisation of the analysand's image of God and the
      assignment of new meaning to it. The resulting changes are shown as contributing
      to psychic growth on the part of both analysand and analyst. The author contends
      that if psychoanalysis dismisses religion as illusion, it is running the risk of
      itself becoming an established religion.

PMID- 9587813
TI  - Sexuality and object love.

PMID- 9587815
TI  - Femininity and masculinity in post-modernism.

PMID- 9587814
TI  - Sexuality in the age of AIDS.

PMID- 9587816
TI  - Trauma and sexuality.

PMID- 9587817
TI  - Childhood sexual theories and childhood sexuality.

PMID- 9587818
TI  - Impotence and frigidity.

PMID- 9587819
TI  - Transvestism and transsexualism.

PMID- 9587820
TI  - Sexuality in clinical psychoanalytical treatment.

PMID- 9587821
TI  - Narcissistic influence on erotic love.

PMID- 9587822
TI  - Contemporary review of psychosexual phases of development.

PMID- 9587823
TI  - On seduction.

PMID- 9587824
TI  - A self-report contrasting concentrated and standard psychoanalysis.

PMID- 9587825
TI  - 'The theory of seduction and the problem of the other' by Jean Laplanche.

PMID- 9587826
TI  - Unilateral Meesmann's dystrophy.
AB  - We report the first case of a unilateral microcystic Meesmann's epithelial
      dystrophy, observed in the left cornea of a 43-year-old patient. The diagnosis
      was verified histologically by the unilateral occurrence of a 'peculiar
      substance' within epithelial cysts and within the cytoplasm of the corneal
      epithelial cells. In an attempt to resolve the patient's frequent corneal
      erosions, we performed an autologous stem cell transplantation from the non
      involved right eye. The results are, so far, satisfactory.

PMID- 9587827
TI  - Retinal manifestations of acute murine typhus.
AB  - PURPOSE: To report the ocular manifestations of acute serologically confirmed
      murine typhus. METHODS: A retrospective analysis of the clinical history,
      photography and fluorescein angiography of two patients with acute murine typhus
      with ocular involvement was conducted. RESULTS: A 38 year old male and a 49 year
      old female were included in the study. Both complained of fever, headache, rash,
      night sweats and pulmonary symptoms. They had noted the recent onset of
      diminished visual acuity and floaters. Examination of the posterior pole revealed
      mild optic nerve head edema (in one patient), intraretinal hemorrhages and small
      localized areas of retinal whitening. The history confirmed that both patients
      had been exposed to fleas and the serologic testing was positive for Rickettsia
      typhi. The systemic and ocular findings resolved after the use of systemic
      antibiotics. CONCLUSION: Rickettsial diseases such as murine typhus should be
      included in the differential diagnosis of otherwise healthy individuals who
      present with an acute systemic febrile illness and retinitis or neuroretinitis.
      SUMMARY STATEMENT: The clinical features of two patients with serologically
      proven acute murine typhus with ocular involvement are presented. Both patients
      presented with a retinal whitening that resolved after treatment.

PMID- 9587828
TI  - Clinical and microbial spectrum of fungal keratitis in Singapore: a 5-year
      retrospective study.
AB  - BACKGROUND: The epidemiology of fungal keratitis varies geographically, but
      commonly occurs in warm, tropical climates. To determine the microbial and
      clinical characteristics of this disease in Singapore, we conducted a 5-year
      hospital-based retrospective study. METHODS: A retrospective review of culture
      positive fungal keratitis at the Singapore National Eye Center and Singapore
      General Hospital, from January 1991 to December 1995. RESULTS: Twenty-nine
      consecutive cases of culture-positive fungal keratitis were seen over the study
      period. The mean age of the cases was 41 years and 23 were males. Amongst the
      varied occupations, 9 were construction workers. The most common cultured
      organisms were Fusarium sp. (52%) and Aspergillus flavus (17%). More than half
      had a history of ocular trauma prior to the development of keratitis, while a
      quarter had antecedent topical corticosteroid therapy. In contrast, only 2
      patients were contact-lens wearers. Despite medical therapy, 10 patients
      eventually required therapeutic penetrating keratoplasties; of these, 6 were
      caused by Fusarium species. CONCLUSION: Fusarium is the commonest cultured
      organism in fungal keratitis in Singapore and is associated with significant
      ocular morbidity.

PMID- 9587829
TI  - Diameter of the optic nerve in idiopathic optic neuritis and in anterior ischemic
      optic neuropathy.
AB  - PURPOSE: There is considerable overlap in the clinical profile of patients with
      idiopathic optic neuritis (ON) and anterior ischemic optic neuropathy (AION). We
      tested the hypothesis that the retrobulbar diameter of the optic nerve may be a
      criterion for the differential diagnosis between ON and AION. METHODS: The
      diameter of the optic nerve was measured by B-scan ultrasonography with the eye
      in an abducted position. Only patients with a unilateral optic neuropathy were
      included, 16 ON patients (mean age 24 years, 5 with and 11 without disc swelling)
      and 9 patients with AION (mean age 72 years). As controls for the ON patients 10
      young normal subjects (mean age 25 years) and as controls for the AION patients
      10 elderly subjects with eye problems not related to the optic nerve (mean age 76
      years) were examined. RESULTS: In the ON patients with disc swelling the diameter
      of the optic nerve was 5.4 +/- 0.5 mm in the affected and 3.0 +/- 0.3 mm in the
      unaffected side. This difference was significant (Wilcoxon-test, p = 0.043). In
      the ON patients without disc swelling the diameter of the optic nerve was 4.4 +/-
      0.4 mm in the affected and 3.0 +/- 0.3 mm in the unaffected side. This difference
      was significant (Wilcoxon-test, p = 0.003). In the AION patients the diameter of
      the optic nerve was 3.0 +/- 0.3 mm on the affected and 2.8 +/- 0.4 mm on the
      unaffected side. This difference was not significant (Wilcoxon-test, p = 0.093).
      Comparing the optic nerves with ON and AION to those of the controls, the
      diameter was significantly enlarged in the nerves with ON and normal in the
      nerves with AION (one factor repeated ANOVA). CONCLUSION: The diameter of the
      optic nerve is increased in ON without disc swelling and even more so in ON with
      disc swelling. The enlargement is probably due to edema of the nerve itself, not
      the surrounding subarachnoidal space. In AION, the diameter of the optic nerve is
      normal. Measuring the diameter of the optic nerve by B-scan ultrasonography is
      particularly useful in the differential diagnosis between ON with disc swelling
      and AION.

PMID- 9587830
TI  - Surgical management of cataract and posterior chamber intraocular lens
      implantation in Fuchs' heterochromic iridocyclitis.
AB  - BACKGROUND: To determine the inflammatory course and level of visual
      rehabilitation after cataract extraction and posterior chamber lens implantation
      in patients with Fuchs' heterochromic iridocyclitis complicated by cataract.
      METHODS: In a clinical trial, 32 eyes (visual acuity of 20/160 or worse) of 30
      patients underwent extracapsular cataract extraction (19 eyes) or lensectomy (13
      eyes) accompanied by posterior chamber intraocular lens implantation. Indirect
      ophthalmoscopy was performed intraoperatively prior to intraocular lens
      implantation and the extent of vitreous haze was assessed. If vitreous haziness
      was 3+ or more, core vitrectomy (two eyes) or three-port pars plana deep
      vitrectomy (four eyes) was performed. RESULTS: After an average follow up of 14.4
      months (6 to 24 months), there was no statistically significant increase in cell
      and flare in the anterior chamber and vitreous or in keratic precipitates
      compared with the preoperative status of the eyes. However, 12% of the eyes
      developed synechiae (anterior and/or posterior) in comparison to preoperative
      condition (p < 0.05). Eight-seven percent of the eyes gained visual acuity of
      20/40 or better (P < 0.005). Using the logistic regression model, a higher level
      of preoperative inflammation was associated with reduced likelihood of gaining
      visual acuity of 20/25 or more (OR = 0.25, 95% CI 0.049, 1.255). The
      complications of surgery were synechiae, 12%; opaque posterior capsule, 12%;
      vitreous loss, 3%; chronic glaucoma, 3%; and retinal detachment, 3%. CONCLUSIONS:
      Implantation of a posterior chamber intraocular lens can be well tolerated in
      patients with Fuchs' heterochromic iridocyclitis. Vitrectomy, whenever indicated
      in addition to cataract extraction, improves visual rehabilitation.

PMID- 9587831
TI  - A case of localized retinal damage in thallium poisoning.
AB  - PURPOSE: To determine the cause of visual impairment and to document the late eye
      disturbances in a case of thallium poisoning. PATIENT: A 44-year-old woman
      presented with a history of repeated attacks of complete alopecia over a period
      of several months, diffuse pain in both legs, transient gastrointestinal
      disturbances, abasia with a progressive paraparesis, paresthesia in the
      fingertips, and polyneuropathy. She complained of slowly progressive visual
      deterioration in both eyes which began about six months after the first attack of
      alopecia. The optic discs showed distinct signs of temporal atrophy together with
      a deep temporal excavation. The Goldmann perimetry revealed an absolute central
      scotoma. Traces of thallium were found in the urine and in the serum. The
      district attorney later discovered that her husband had been trying to poison her
      with thallium. METHODS: The clinical and electrophysiological examinations
      included visual evoked potentials (VEP) and electroretinography (flash ERG,
      multifocal ERG and pattern ERG). RESULTS: The VEP showed a reduction in amplitude
      and a prolonged latency indicating a conduction block. The pattern ERG was
      initially normal. At a follow-up examination 6 years later, a slight amplitude
      reduction in the pattern ERG was found. The multifocal ERG showed a diminished
      amplitude in the center of the retina (up to +/- 10 degrees visual angle).
      CONCLUSIONS: The electrophysiological investigations in our patient--who had an
      optic atrophy--indicated a conduction block of the retinal nerve fibers (VEP) and
      an additional lesion at or before the retinal bipolar cells (multifocal ERG),
      localized in the central +/- 10 degrees. These findings suggest that thallium
      poisoning can lead to a combined lesion of the retinal nerve fibers and the
      neural retina.

PMID- 9587832
TI  - Master Samuel Ebrej ophthalmic surgeon of Dubrovnik and contracts relating to
      medical services dating from 1414.
AB  - Throughout the Middle Ages, Dubrovnik maintained active and regular commercial
      and maritime contacts with various cities and states of the Mediterranean. These
      activities led to the organisation of a health care system and the development of
      medicine. With respect to the economic, commercial and maritime aspects of the
      culture of this city state, Dubrovnik became open to the civilising progress of
      the region and period. The brief visit of the Mediaeval ophthalmologist, Master
      Samuel Ebrej supports this fact.

PMID- 9587833
TI  - Intraimage reproducibility of measurements in the macular area using a
      computerized system.
AB  - An accurate analysis of the morphological changes which take place during
      pathological processes of the posterior pole is important for a correct diagnosis
      and therapeutic approach. The purpose of the study was to determine the
      intraobserver and interobserver reproducibility of the Image-net system 100
      (Topcon, Japan) to take measurements on the retina. The program 'Linear/Areal
      Measurement functions' of Image-net system 100 which is an image digitalization
      technique, was tested. Twelve patients were consecutively selected from the
      patients of the Retina Center of the Department of Ophthalmology, University of
      Genoa. Three images of each eye were taken from each subject and only the best
      image was used in this study. The intraobserver and interobserver reproducibility
      of both the distance between two pre-set points (linear measurement), and the
      perimeter and area of preselected retinal zones were calculated. The
      repeatability (or intraobserver reproducibility) of the linear sizes was measured
      by the coefficient of variation and ranged from 0.32% to 7.38%, while the
      interobserver reproducibility ranged from 0.46% to 5.22%. The repeatability and
      reproducibility of the perimeters ranged from 0.72% to 9.63% and from 0.6% to
      5.7%, respectively, while the repeatability and reproducibility of the areas
      ranged from 0.72% to 9.63% and from 0.6% to 5.7%, respectively. Although the
      results were quite good, the quality of the image of the fundus and the number of
      observers influenced the coefficient of variation; furthermore, the anatomy of
      the areas to be measured and the computer 'mouse' could increase the value of the
      coefficient of variation.

PMID- 9587834
TI  - Branch retinal vein occlusion and macroaneurysms.
AB  - BACKGROUND: Macroaneurysms can represent common consequences of branch retinal
      vein occlusion (BRVO). The aim of the present study is to evaluate the clinical
      and angiographic aspects of 31 cases of branch retinal vein occlusions (BRVO) in
      which retinal macroaneurysms developed, in an attempt to analyze their pathogenic
      features. METHODS: One hundred and sixty-one consecutive patients affected by
      BRVO were considered. Each patient underwent an opthalmological examination
      including fluorescein angiography, at an average interval of two months (range: 1
      4 months) from the onset of the disease, with a mean follow-up of 43 months
      (range: 32-56 months). The macroaneurysms were subdivided according to size into
      small (from 100 to 149 microns), medium (from 150 to 249 microns), and large
      (greater than 250 microns), and according to origin into arterial, venous,
      capillary and collateral-associated. RESULTS: Thirty-one patients (19.3%)
      developed retinal macroaneurysms. The total number of detected macroaneurysms was
      51; ten (19.6%) were large, 21 (41.2%) were of medium-size and 20 (39.2%) were
      small in dimension. Three lesions were of arterial origin, 22 were capillary and
      26 were from collateral vessels. In 27 patients (87.1%) the lesions were located
      outside the macular region, and in 4 patients (12.9%) in the macular region.
      Patients with retinal macroaneurysms did not show a different prevalence of
      capillary non-perfusion when compared with others. With regard to the number of
      retinal venous collaterals patients with macroaneurysms developed fewer than
      other patients, and the difference was statistically significant (p < 0.001).
      CONCLUSION: The insufficient number of retinal venous collaterals can be
      considered the most contributory factor in the development of macroaneurysms
      secondary to BRVO.

PMID- 9587836
TI  - Ophthalmic complications of vaccines against hepatitis B virus.

PMID- 9587835
TI  - Scanning and transmission electron microscopic findings during RPE wound healing
      in vivo.
AB  - OBJECTIVE: To examine the scanning (SEM) and transmission (TEM) electron
      microscopic features of an in vivo rabbit model of retinal pigment epithelial
      (RPE) wound healing. METHODS: Hydraulic debridement of the RPE was performed in
      one eye of each of 35 pigmented rabbits using a pars plana vitrectomy approach.
      Five of the 35 eyes were examined by either SEM or TEM on each of the following
      postoperative days: 0, 2, 4, 7, 14, 28 and 56. RESULTS: TEM revealed that
      hydraulic RPE debridement results in only focal damage to the RPE basement
      membrane portion of Bruch's membrane and that this damage is repaired by day 7
      without ultrastructural sequelae. SEM and TEM disclosed that the RPE cells at the
      margin of the debrided bed become flattened and enlarged and evolve a
      cytoskeletal reorganization with altered apical-basal polarity consistent with
      the development of a migrating phenotype. This is followed by gradual restoration
      to a more normal stationary RPE phenotype after initial closure
      (reepithelialization) of the RPE defect on day 7. RPE hyperplasia also occurs and
      may contribute to this repair process. Tight junctions are re-established among
      the apical surfaces of monolayered and multilayered RPE cells by day 7,
      coinciding with the restoration of the blood outer retinal barrier. CONCLUSION:
      Hydraulic debridement of the RPE in vivo is a useful investigational model that
      provides important insight into the pathogenesis of outer retinal disorders and
      their treatment with such techniques as submacular surgery or RPE
      transplantation.

PMID- 9587838
TI  - Aqueous vascular endothelial growth factor increases in anterior segment ischemia
      in rabbits.
AB  - Both long posterior ciliary arteries were occluded or the three extraocular
      muscles were tenotomized to produce anterior segment ischemia in rabbits, and the
      aqueous levels of vascular endothelial growth factor (VEGF) were measured. The
      occlusion of both long posterior ciliary arteries led to clinical and
      histological anterior segment ischemia in varying degrees. The aqueous VEGF
      levels increased significantly compared with controls on all days examined (Mann
      Whitney U test: day 1, P = 0.0039; day 4, P = 0.0065; day 7, P = 0.0039; day 14,
      P = 0.0104), while the levels at days 7 and 14 decreased significantly compared
      with those at day 4 (Wilcoxon signed-rank test; day 4 to day 7 and day 4 to day
      14, P = 0.0464). In contrast, tenotomy of the three extraocular muscles resulted
      in no histological changes. The VEGF levels increased significantly compared with
      controls at day 1 and day 4 decreased significantly compared with those at day 1
      (Wilcoxon signed-rank test, P = 0.0499). Aqueous VEGF levels represent the
      severity of anterior segment ischemia and could be used as an indicator for the
      extent of ischemia.

PMID- 9587837
TI  - Collagenolytic activity of keratocytes cultured in a collagen matrix.
AB  - To study the mechanism of collagen degradation by keratocytes, we developed the
      new in vitro model in which keratocytes were cultured three-dimensionally in a
      collagen matrix. Subcultured rabbit keratocytes were embedded in a type I
      collagen matrix and cultured in serum-free medium. Collagenolytic activity of the
      cells was determined by measuring the amount of hydroxyproline released into the
      medium from degraded collagen. Activities of collagenase in the medium were also
      measured, using collagen labeled with fluorescein isothiocyanate as a substrate.
      The presence of plasminogen was required for collagen degradation by keratocytes.
      In the presence of plasminogen, the amount of collagen degradation depended on
      both the cultivation period and the number of cells. The addition of interleukin
      1 (IL-1) stimulated the collagen degradation in a dose-dependent manner. This
      stimulatory effect of IL-1 was completely inhibited by the addition of IL-1
      receptor antagonist (IL-1ra). Collagenase activity in the medium was stimulated
      by the addition of IL-1, and IL-1ra antagonized this stimulatory effect. These
      findings indicate that our present model may be useful for investigating the
      mechanism of collagen degradation by keratocytes.

PMID- 9587839
TI  - Bovine trabecular cells produce TIMP-1 and MMP-2 in response to mechanical
      stretching.
AB  - Bovine trabecular cells in growth phase were exposed to cyclic mechanical
      stretching of the bottom of a culture dish at a cycle of 30 seconds for 72 hours.
      The stretched cells produced significantly larger amounts of metalloproteinase-2
      (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) after 72 hours,
      compared with cells in nonstretched control. In contrast, TIMP-2 and MMP-9 levels
      were not influenced by mechanical stretching. Trabecular cells would modify
      extracellular matrix in response to such mechanical stimuli as bending of
      trabecular meshwork or aqueous flow by the production of TIMP-1 and MMP-2.

PMID- 9587840
TI  - A comparative study of latanoprost (Xalatan) and isopropyl unoprostone (Rescula)
      in normal and glaucomatous monkey eyes.
AB  - Latanoprost (PhXA41, Xalatan) and isopropyl unoprostone (UF-021, unoprostone,
      Rescula) two new prostanoid derivatives, have been shown to reduce intraocular
      pressure (IOP) significantly in patients with glaucoma or ocular hypertension.
      This study was designed to compare the ocular hypotensive effects of latanoprost
      and unoprostone in cynomologus monkeys with glaucoma and characterizes the
      prostanoid's mechanisms of action in normal cynomolgus monkey eyes. Intraocular
      pressure was measured daily at 0, 0.5, and 1 hour and hourly for 5 additional
      hours during 1 baseline day, 1 vehicle-treated day, and 5 days of therapy with
      either 0.005% latanoprost or 0.12% unoprostone applied twice daily, at 9:30 AM
      and 3:30 PM, to the glaucomatous eye of eight monkeys with unilateral laser
      induced glaucoma. Outflow facility was measured in six normal monkeys 3 hours
      prior to dosing and 1 hour after unilateral dosing with either drug. Aqueous
      humor flow rates were measured in six normal monkeys hourly for 4 hours on 1
      baseline day and on 1 treatment day beginning 1 hour after administration of
      either drug to one eye. Intraocular pressure was significantly (P < 0.005)
      reduced after the first application for 4 hours with latanoprost and for 2 hours
      with unoprostone, up to 5.4 +/- 0.8 mm Hg (mean +/- SEM) (latanoprost) and 3.8 +/
      0.5 mm Hg (unoprostone). Intraocular pressure was significantly (P < 0.005)
      reduced for at least 18 hours following each PM dose of latanoprost. Intraocular
      pressure was not reduced (P > .05) 18 hours after each PM dose of unoprostone. An
      enhancement of the ocular hypotensive effect was observed from day 1 to day 5
      with repeated dosing of either drug. Latanoprost produced a greater magnitude of
      IOP reduction for a longer duration of time than unoprostone after each
      application. Neither drug altered outflow facility or aqueous humor flow rates.
      Latanoprost and unoprostone appear to reduce IOP in monkeys by enhancing
      uveoscleral outflow. Latanoprost appears to be more efficacious and potent than
      unoprostone in reducing IOP in glaucomatous monkey eyes.

PMID- 9587841
TI  - Use of dynamic and colored stereogram to measure stereopsis in strabismic
      patients.
AB  - The effectiveness of movement or color has not been well studied in assessing
      stereopsis in patients with strabismus. We developed a new stereotest equipped
      with both a monochromatic dynamic random dot stereogram (DRDS) and a static
      colored stereogram (SCS) and examined the stereopsis of patients with strabismus.
      Three-dimensional (3D) images were displayed on a liquid crystal display equipped
      with a parallax barrier system, allowing 3D images to be seen independently by
      each eye without glasses. A DRDS with maximum disparity of 3200 seconds of arc
      was displayed having front-rear movement. An SCS displaying cartoon characters
      with disparities of 400 seconds of arc was also tested and compared with the
      Titmus stereotest. A total of 52 strabismic patients were tested. The DRDS showed
      a significantly higher (P = 0.02) detection rate of stereopsis (39/52, 75%) as
      compared with the Titmus fly test (28/52, 54%). The SCS did not show any
      difference in the stereopsis detection rate (24/521, 46%) when compared with the
      Titmus animal test (20/52, 38%). Thus, the DRDS was useful in detecting
      stereopsis in patients without stereopsis on the conventional Titmus fly test,
      while the SCS did not show any difference when compared with the Titmus animal
      test. The DRDS may examine a different aspect of stereopsis from the static
      stereopsis measured by the Titmus stereotest or SCS.

PMID- 9587842
TI  - Acridine orange staining for rapid diagnosis of Acanthamoeba keratitis.
AB  - Acanthamoeba keratitis is uncommon, but one of the most severe infectious
      diseases of the cornea. Delayed diagnosis or misdiagnosis as bacterial or herpes
      simplex keratitis leads to extensive corneal inflammation and profound visual
      loss. Therefore, accurate and rapid diagnosis of Acanthamoeba keratitis is
      essential for successful treatment and good prognosis. We evaluated the
      usefulness of acridine orange staining from corneal scrapings and contact lens
      solutions for the rapid diagnosis of four consecutive cases of Acanthamoeba
      keratitis. Gram stain and culture on nonnutrient agar plates with Escherichia
      coli overlay were also made. Corneal scrapings stained with acridine orange
      revealed yellow-to-orange polygonal, cystic structures consistent with the
      appearance of Acanthamoeba among inflammatory cells and the corneal epithelial
      cells. The contact lens case solutions of two patients also showed numerous cysts
      with double wall. Some organisms from the third patient were identified as
      Acanthamoeba castellani and others as Acanthamoeba lugdunensis. Based on the
      acridine orange staining results in four cases of Acanthamoeba keratitis, this
      stain is recommended as a simple and reliable method for the rapid diagnosis of
      this disease.

PMID- 9587843
TI  - Clinicopathologic study of satellite lesions in nontuberculous mycobacterial
      keratitis.
AB  - Multifocal stromal infiltrates or "satellite lesions" have been considered a
      characteristic feature of fungal keratitis. We examined two patients with
      nontuberculous mycobacterial keratitis who clinically presented with satellite
      lesions. The keratitis consisted of multifocal stromal infiltrates with
      indistinct white and fluffy margins. Both patients received topical fortified
      amikacin therapy with poor response. Lamellar keratectomy or penetrating
      keratoplasty was performed, respectively, in the two patients because of
      progressive stromal thinning and enlarging satellite lesions.
      Histopathologically, the main lesions consisted of dense infiltration of
      inflammatory cells with numerous acid-fast bacilli, while the satellite lesions
      were composed chiefly of inflammatory cells with fewer mycobacteria. Besides
      fungal keratitis, nontuberculous mycobacterial keratitis should also be
      considered when satellite lesions are present.

PMID- 9587844
TI  - The effect of altitude on radial keratotomy.
AB  - The authors analyzed refractive results of patients who underwent radial
      keratotomy (RK) at sea level and high altitude and evaluated the effects of the
      altitude. A total of 102 eyes undergoing RK procedures performed in two clinical
      centers having different altitude were analyzed. The results compared between
      subjects who had undergone RK at sea level (Istanbul/Turkey) and at an altitude
      of 5750 feet (Van/Turkey) were compared. Subjects were 19-42 years old with
      myopia from -4.00 to -12.00 diopters (D). The average preoperative spherical
      equivalent cycloplegic refractions (SECR) were -8.01 +/- 1.86 D and -6.99 +/-
      2.15 D in the Istanbul and Van groups, respectively. These were divided into
      subgroups according to myopia degree and number of incisions and optic zone size.
      The RK procedures were performed by the same surgeon with diamond blade in
      standard Russian style. The average changes in SECR were 5.09 +/- 1.29 D and 6.50
      +/- 2.24 D in subjects who had undergone RK at sea level and at 5750 feet,
      respectively. There was a significant difference between the subgroups (P <
      0.0002). This difference was especially higher in the high myopia subgroups.
      Additionally, we obtained a partial relation between increase of RK incision
      number and SECR change at high altitude but not at sea level. No notable
      regression and progression were seen in the 3 months of follow-up at high
      altitude. These results support hypotheses suggesting both corneal hypoxic
      expansion in the area of RK incisions, which may lead to central corneal
      flattening, and barometric pressure directly altering corneal shape, which is
      responsible for the hyperopic shift induced by altitude. Ophthalmologists
      performing RK surgery at high altitude had better consider redesigning their RK
      nomograms in light of these findings. However, when the nomogram used at sea
      level was used at high altitude, the subjects became hyperopic.

PMID- 9587845
TI  - Long-term observation of infants with macular hemorrhage in the neonatal period.
AB  - Ten infants with macular hemorrhage in the neonatal period were tested to assess
      visual acuity, stereopsis, and ocular position. Contrast sensitivity was examined
      in three of them. The duration of hemorrhages was 1 month in four patients, 1.5
      months in one patient, 2 months in two patients, 3 months in one patient, 4
      months in one patient (corrected gestational 3 months), and 5 months in one
      patient (corrected gestational 2.5 months). None of the patients developed
      deprivation amblyopia or visual loss due to abnormality of macula. The results
      suggest that there is essentially no risk of visual deprivation for 3 months
      after birth. If there is any poor visual acuity, abnormal ocular position,
      abnormal eye movement, or poor stereopsis in the infant with neonatal macular
      hemorrhage, we have to elucidate the cause of the symptoms.

PMID- 9587847
TI  - Relationship between visual field defect and multifocal electroretinogram.
AB  - We investigated the effect of artificial parafoveal scotomata on the multifocal
      electroretinogram (M-ERG). M-ERGs were recorded from normal subjects using a
      monitor with several different sizes of black paper attached. A lower response
      density area around the 10 to 15 degree parafoveal region was not recognized for
      scotomata up to 3 degrees but was observed in scotomata above 5 degrees (visual
      angle) in the field topography of M-ERG. The shape of the scotomata was not
      circular but somewhat oval. The results from two cases of parafoveal retinal
      degeneration accorded well with this basic study.

PMID- 9587846
TI  - Multifocal electroretinograms in normal subjects.
AB  - Multifocal electroretinography (ERG), developed by Sutter in 1992, is a method of
      recording the spatial distribution of focal ERG in a short time period using
      multi-input stimulation. Using this technique, we can detect the spatial extent
      and severity of damage to the macula. In this study, we recorded multifocal ERGs
      from 20 eyes of 20 normal subjects and analyzed the topographical properties of
      responses. In every subject, a negative wave followed by a positive wave could be
      recorded and we named them the N1-wave and the P1-wave, respectively. The
      amplitudes of the N1-wave and the P1-wave were the largest in the fovea, and they
      became smaller with eccentricity. In the P1-wave amplitude, the greatest
      intersubject variability was observed at the fovea. The N1 and P1 latencies were
      shorter in the upper retina than in the lower retina. The amplitude was larger in
      the upper retina than in the lower retina, which suggests the functional
      superiority of the upper retina. There was no statistical difference in latency
      and amplitude between the nasal and the temporal retina. We found no statistical
      difference between the responses of the papillomacular bundle and those of the
      temporal retinal area. The mapping obtained by multifocal ERG was useful as
      objective perimetry.

PMID- 9587850
TI  - The future of heart valve standards.

PMID- 9587849
TI  - Temporal modulation transfer function in normal-tension glaucoma patients.
AB  - A new screening test involving the Flicker System was used to measure temporal
      modulation transfer function in an effort to detect early-stage glaucoma. The
      study involved 64 normal-tension glaucomatous eyes and 65 normal control eyes.
      Patients with early-stage glaucoma (stage 0-1 of the Aulhorn-Greve
      classification) showed a significant modulation decrease in the 20-45 Hz range,
      compared to the modulation in normal eyes (P < 0.05). Patients with moderate
      stage glaucoma (stage 2-3) also exhibited significantly decreased modulation
      values in the 14-55 Hz range. In the 25-45 Hz range, the reduction of modulation
      in patients with diffuse visual defect was more profound than in those with
      localized or mixed defects. The results of the present study suggest the presence
      of diffuse visual function deficit in glaucoma.

PMID- 9587848
TI  - Weak association between retinopathy of prematurity and neurological disorders in
      childhood.
AB  - An attempt was made to elucidate the association between retinopathy of
      prematurity (ROP) and neurological disorders in infants of very low birth weight.
      In this retrospective study, 1081 Japanese children weighing less than 1500 g at
      birth were classified into four subgroups according to birth weight. In each
      subgroup, the association among cerebral palsy (CP) or mental retardation (MR)
      and ROP, treated ROP, and cicatricial ROP was analyzed statistically. In the
      population as a whole, CP and MR were positively associated with ROP. However, in
      the birth weight subgroup analysis, no significant association was found. We can
      conclude that there is a weak association between ROP and CP or MR.

PMID- 9587851
TI  - Replacement heart valves and performance standards.
AB  - The international use of medical device standards is expanding for both economic
      and regulatory reasons. It is no longer adequate to have standards that only
      specify measurement methods and labeling for a product. An effort needs to be put
      forth between industry, academia and government to promote standards that also
      include a minimum set of acceptable performance criteria. This will allow for a
      less subjective evaluation of the conformance of the medical device to the
      appropriate standard as well as promote a uniform set of minimal performance
      expectations for a class of products among consumers.

PMID- 9587852
TI  - Fluid dynamic studies for the year 2000.
AB  - The authors recommend changes to the paradigm employed in the current ISO Heart
      Valve Standard (ISO 5840) so that future patients who receive a heart valve
      prosthesis are assured of a device that will function with minimal complications
      for at least 25 years. Based on valve failures of the past decade, it is clear
      that current standards are inadequate because present-day Standards and
      Regulatory Agencies operate in a manner which inhibits innovation and creativity.
      Thus, engineers and scientists in this field react to problems, rather than
      proact. As we approach the new millennium, the authors consider it time to
      rethink the ground rules.

PMID- 9587853
TI  - Cavitation potential of pyrolytic carbon heart valve prostheses: a review and
      current status.

PMID- 9587854
TI  - Durability/wear testing of heart valve substitutes.
AB  - BACKGROUND AND AIMS OF THE STUDY: The current standards for accelerated heart
      valve testing have considerable differences in test conditions. Another problem
      arises from the fact that such test systems are not standardized at all. It was
      shown earlier that different test systems generate totally different valve
      loading, even if operating at standard conditions. The present study aimed to
      improve this unsatisfactory situation and to develop a new concept where actual
      loading of valves is measured either in vitro or in vivo under physiologic
      conditions and subsequently to reproduce these conditions during accelerated
      testing. METHODS: Integral loading forces at valve closure were measured for
      several valve types using a piezoelectric force ring within a real-time
      circulatory mock loop under physiologic conditions. This facilitated definition
      of a physiologic loading range. Physiologic loading was subsequently reproduced
      in a single-chamber accelerated test system. Working conditions obtained in terms
      of stroke, bypass flow and compliance served as design criteria for a new test
      chamber and a complete 12-chamber accelerated testing system. RESULTS: The
      integral loading obtained using the force ring showed a correlation with previous
      in vitro and in vivo results of strain-gauged valves. Loading forces for
      mechanical valves are about one order of magnitude higher than for bioprosthetic
      valves and are strongly related to cardiac output for both valve types. At
      physiologic loading, however, the differential pressures across the valves are
      considerably below those given in FDA guidelines. CONCLUSIONS: This pilot study
      demonstrates that physiologic valve loading is reproducible over a wide range
      under appropriate testing conditions. It also showed that, at the back-pressures
      of the current standards, the loading forces during accelerated testing exceed
      the real-time loading forces by far and, thus, may provide unrealistically high
      valve loads. These initial findings indicate that amendments of the currently
      valid standards may be need to be accorded.

PMID- 9587855
TI  - Current state of in vivo preclinical heart valve evaluation.
AB  - The use of animals to predict prosthetic valve performance in humans has now been
      in operation for over 25 years. Studies have focused on improvements in
      structural integrity, anti-thrombogenicity and anticalcification, and provide
      extensive in vivo analysis and validation of a valve before its clinical
      evaluation. Many animal models have been developed for such investigations,
      including calves, goats, pigs, baboons, dogs and adult sheep. Recent models used
      to assess prosthetic mitral valves have involved site-specific testing in several
      species; the present study represents the largest series of orthotopically
      implanted stentless bioprosthetic aortic valves and the first to utilize a
      juvenile sheep model for the aortic position.

PMID- 9587856
TI  - Clinical evaluation and analysis of heart valve substitutes.
AB  - We discuss the clinical assessment of heart valve substitutes, primarily with
      regard to pre-market evaluation. We concentrate on the current FDA heart valve
      guidance document. This guidance is self-acknowledged to be an evolving document,
      scheduled to be revised between three and five years after its initial release on
      December 1993. We outline the history and some of the strengths of the present
      system, and discuss areas for possible improvement. We selected one important
      statistical issue to address thoroughly how to compute the confidence limit of a
      linearized rate.

PMID- 9587857
TI  - Determinants of calcium uptake of bovine pericardium for heart valve replacement:
      results of in vitro studies.
AB  - BACKGROUND AND AIMS OF THE STUDY: Reduction of biomaterial calcification is an
      important aim in the basic research of biological heart valves. An in vitro model
      was used to investigate the influence of serum calcium concentration and surface
      coverage with cells or basal proteins on calcium uptake of bovine pericardium.
      METHODS: Samples of glutaraldehyde-tanned bovine pericardium, stored in
      formaldehyde and detoxified with borohydride were incubated for two weeks with
      cell culture medium containing low (1.0 mmol/l) or physiologic (2.3 mmol Ca/l)
      calcium concentration. Specimens were either unseeded, completely surface-covered
      with rat fibrocytes (rf) or fibrin (fi), or incompletely seeded with rabbit cells
      (re). Quality of surface coverage was assessed by surface scanning electron
      microscopy and calcium content by atomic absorption spectroscopy. RESULTS: Serum
      calcium had a significant influence on calcium uptake (low versus physiological
      (1.58 +/- 2.45 mg/g versus 8.10 +/- 1.73 mg/g wet wt, p < 0.001). This may
      explain early calcification of bioimplants in children and patients on dialysis.
      Surface coverage significantly reduces calcium uptake (fi, 1.20 +/- 0.41 mg/g,
      rf, 4.20 +/- 1.70 mg/g, p < 0.001) but complete coverage is necessary (re, 6.98
      +/- 1.64 mg/g, NS). CONCLUSIONS: In vitro testing of calcium uptake has proven to
      be a valuable tool for evaluation of biomaterial calcification.

PMID- 9587858
TI  - Pathologic findings in explanted clinical bioprosthetic valves fabricated from
      photooxidized bovine pericardium.
AB  - BACKGROUND AND AIMS OF THE STUDY: The study aim was to assess tissue quality and
      host-biomaterial interactions in clinical bioprostheses fabricated from bovine
      pericardium preserved by dye-mediated photooxidation, but not glutaraldehyde
      pretreated. METHODS: Ten aortic valves explanted for regurgitation after 8-23
      months' function from 10 patients aged 67-83 years were analyzed by gross and
      dissecting microscope examination, radiography and light microscopy. RESULTS:
      Each valve had one to several commissural-basal tears (5 mm) to complete leaflet
      detachment (four valves). The pattern of tearing was consistent among valves and
      suggested that a mechanism of design-related proximal inflow surface cuspal
      abrasion against Dacron cloth was contributory. Mild cuspal sagging/stretching
      was noted in five valves, pannus overgrowth was mild, and there was no evidence
      of infection or macroscopic thrombus. Microscopically, tissue distant from tears
      in all valves had an essentially intact but acellular collagenous matrix, was
      devoid of residual connective tissue cells and host inflammatory cells, with mild
      fragmentation of the inflow collagen bundles, and showed no evidence of
      endothelialization. Despite radiographs uniformly negative for mineralization,
      focal intrinsic cuspal microcalcification was noted histologically in four
      valves. CONCLUSIONS: Design-related and largely abrasion-induced tearing caused
      failures of this cohort of photooxidized pericardial valves. Nevertheless, this
      nonglutaraldehyde-preserved photofixed pericardial tissue from valves suffering
      design-related cuspal tears to two years postoperatively remained without
      significant degradation, inflammation, infection, thrombus, pannus or
      calcification.

PMID- 9587860
TI  - Detoxification process for glutaraldehyde-treated bovine pericardium: biological,
      chemical and mechanical characterization.
AB  - BACKGROUND AND AIMS OF THE STUDY: Glutaraldehyde cross-linked bovine pericardium
      was post-treated with homocysteic acid in order to bond unreacted glutaraldehyde
      groups, and preserved in aldehyde-free solution to reduce the toxicity and
      calcification potential of the tanned tissue. The study aim was to verify the
      efficacy and preservation of chemical and mechanical properties of pericardial
      tissue treated in this way. METHODS: Detoxification efficacy was tested by
      measuring free aldehyde groups and by in vitro cultivation of human endothelial
      cells on pericardial samples. Material stability tests included mechanical
      characterization, shrink temperature measurement, pronase digestion resistance
      and amino acid analysis after acid hydrolysis. The effect of treatment on fatigue
      resistance was evaluated by monitoring changes in permeability and compliance
      caused by 15 x 10(6) cycles of pulsatile stress. RESULTS: Detoxified samples
      showed negligible glutaraldehyde residues and significantly improved endothelial
      cell proliferation compared with conventionally treated samples. Chemical and
      mechanical properties were similar in detoxified and glutaraldehyde-treated
      samples. Tissue fatigue behavior was not modified by homocysteic acid treatment.
      CONCLUSION: Homocysteic acid treatment effectively reduces toxicity but does not
      affect the stability of glutaraldehyde cross-linked pericardium.

PMID- 9587859
TI  - Pathology of the Pericarbon bovine pericardial xenograft implanted in humans.
AB  - BACKGROUND AND AIMS OF THE STUDY: Pericarbon is a new-generation bovine
      pericardial bioprosthesis designed to withstand mechanical wear. Following
      optimal in vitro testing and animal experiments, clinical trials were initiated
      in many European centers and explants sent to our department for pathological
      evaluation. This included gross, radiographic, histologic and ultrastructural
      investigations. METHODS: Between 1986 and 1996, 24 bioprostheses (eight aortic,
      11 mitral, two mitro-aortic, one tricuspid) were collected from 22 patients (10
      males and 12 females; mean age 57.0 +/- 18.9 years) either at autopsy (nine) or
      reoperation (15). RESULTS: Ten bioprostheses explanted < 2 months after surgery
      were either normal or failed because of surgical problems or non-structural
      causes. Among the other 14 bioprostheses (mean placement 41.9 +/- 23.6 months;
      range: 7 to 90 months), structural deterioration occurred in seven and was due to
      dystrophic calcification with stenosis in five (three aortic, two mitral), mixed
      lesion in one (mitral), and incompetence in one by calcium-related commissural
      tear (mitral). At the ultrastructural level, calcification was detected either on
      cell debris or upon collagen fibers. No bioprosthesis failed because of fibrous
      tissue overgrowth. Of the remaining seven bioprostheses, vegetative endocarditis
      occurred in two, thrombosis in one, and aseptic paravalvular leak in one; whereas
      three showed no signs of dysfunction. CONCLUSIONS: This pathologic experience
      with the Pericarbon valve showed calcification to be the main cause of late
      structural failure, causing mainly cusp stiffness and bioprosthesis stenosis.
      Tissue rupture or abrupt dysfunction never occurred. Thus, prevention of
      mineralization remains the main challenge.

PMID- 9587861
TI  - Use of bovine pericardial tissue for aortic valve and aortic root replacement:
      long-term results.
AB  - BACKGROUND AND AIMS OF THE STUDY: The study aimed to determine the clinical
      performance of bovine pericardial aldehyde-treated products alone or in
      combination with aortic leaflets of porcine origin. These included a composite
      porcine stentless aortic valve attached to a scalloped pericardial tube (BSAV),
      and valved and non-valved bovine pericardial conduits for use in left-sided heart
      lesions (BPG). METHODS: For BSAV grafts, between January 1990 and August 1996,
      163 patients (119 males) had their aortic valves replaced by SJM Biocor BASV.
      Mean age was 37.9 +/- 17.6 years (range: 1 to 76 years). Rheumatic heart disease
      sequelae (n = 72) and replacement of a prosthetic heart valve (n = 46) were
      predominant. Preoperative NYHA functional class showed 90 patients (55.2%) in
      class III and 50 (30.7%) in class IV. BPVC and NVPC grafts were used in 166
      patients: acute aortic dissection was the main indication in 52 (31.3%) and
      chronic in 36 (21/7%). The ascending aorta was involved in 141 patients (84.9%);
      grafts were seldom used at other sites. In most patients the graft implanted was
      either a non-valved (n = 79) or a valved (n = 75) pericardial conduit. Twelve
      patients had a localized lesion and required a patch repair. RESULTS: For BASV
      grafts, the non-valve-related hospital mortality rate was 4.9%. There were 14.7%
      non-fatal complications with full recovery of all patients. Mean follow up in 141
      patients was 3.0 +/- 1.4 years (range: 1 month to 7.2 years); 14 patients were
      lost to follow up. Late, non-conduit-related, mortality occurred in seven
      patients (4.9%). Eight patients underwent reoperation. The current clinical
      follow up of 127 patients has shown 118 (92.9%) with competent valves and nine
      (7.0%) with mild stable aortic insufficiency. For BPVC and NVPC grafts, hospital
      mortality rate was 16.9%, death being related to poor preoperative clinical
      condition. Postoperative follow up was accomplished in 125 patients; reoperation
      was necessary in seven patients. Histology showed good tissue preservation up to
      five years; echocardiography revealed satisfactory findings. No valved conduit
      had to be reoperated for valve or pericardial tissue wear. CONCLUSIONS: Clinical
      results of left-sided heterologous pericardial grafts have shown excellent
      performance over time. The BASV (over seven years) and BPVC and NVPC (eight
      years) have demonstrated superior results as aortic valves alone or in
      combination with a pericardial conduit.

PMID- 9587862
TI  - Mapping of bovine pericardium: physical and histopathologic tests.
AB  - BACKGROUND AND AIMS OF THE STUDY: This study was performed to identify the
      physical and histopathologic characteristics of different sections of
      glutaraldehyde-tanned bovine pericardium. METHODS: Ten pericardial sacs were
      obtained from animals aged from 18 to 36 months. Physical tests included
      shrinkage and mechanical resistance (rupture, elongation, tenacity index).
      Collagen and elastic fibers were evaluated in Gomori's trichrome-stained
      sections, hematoxylin and eosin, by PAS and Verhoeff's method. Studied areas were
      proximal to the great arteries, and the right atrial, right ventricular, left
      ventricular and left atrial regions. RESULTS AND CONCLUSIONS: Results showed that
      bovine pericardium does not have enough regional differences to identify any
      single region for bioprosthesis manufacture. However, histopathology showed
      better preservation of collagen and elastic fibers in the right ventricular
      region, implying that this area is more adequate as bioprosthetic material.

PMID- 9587863
TI  - Valve prosthesis-patient mismatch: an update.

PMID- 9587864
TI  - Impact of prosthesis-patient mismatch on hemodynamic and symptomatic status,
      morbidity and mortality after aortic valve replacement with a bioprosthetic heart
      valve.
AB  - BACKGROUND AND AIMS OF THE STUDY: Previous studies have shown that the effective
      orifice area of an aortic prosthetic valve may be too small in relation to the
      patient's body surface area, resulting in abnormally high gradients. The
      consequences of this condition, termed prosthesis-patient mismatch, have not been
      fully studied. The study objective was to determine if the condition has a
      detrimental effect on symptomatic and hemodynamic status, morbidity and mortality
      of patients undergoing aortic valve replacement. METHODS: A cohort of 392
      patients was prospectively followed for up to seven years after implantation of a
      Medtronic Intact bioprosthesis. Doppler echocardiography was performed annually
      in 72 patients. Based on previous studies, presence of mismatch was defined as an
      indexed valve area < or = 0.85 cm2/m2. RESULTS: Mismatch was associated with less
      postoperative improvement of NYHA functional class (p < 0.009) independently of
      other predictors, such as age and preoperative functional class, but had no
      significant impact on patient survival (mismatch: 75 +/- 4%, no mismatch: 79 +/-
      3%; p = 0.59) and valve-related morbidity up to seven years. Cardiac index was
      similar in patients with and without mismatch up to three years after operation
      but decreased significantly thereafter only in patients with mismatch (-0.54 +/-
      0.32 versus -0.17 +/- 0.49 l/min/m2; p = 0.04). Likewise, the mean
      transprosthetic gradient, which was higher at one year after operation in
      patients with mismatch (22 +/- 8 versus 15 +/- 7 mmHg), increased significantly
      (+6 +/- 6 versus +1 +/- 1 mmHg; p = 0.008) only in this group during follow up.
      CONCLUSIONS: Patients with mismatch have less symptomatic improvement and worse
      hemodynamics that continue to deteriorate with time. However, medium-term
      prognosis (up to seven years) is relatively good. Further studies are necessary
      to determine the longer-term effects of mismatch on morbidity and mortality.

PMID- 9587865
TI  - Intermediate follow up of the TEKNA bileaflet valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to collect intermediate
      clinical data on the TEKNA bileaflet valve. METHODS: This nine-center clinical
      study involved 884 patients implanted between June 1990 and October 1993. The
      population consisted of 522 (59.0%) males and 362 (41.0%) females. Mean age at
      implant was 59.1 +/- 11.8 years (range: 14.7 to 88.4 years). Indication for valve
      replacement was dependent on the position: stenosis was the predominant reason in
      the aortic position; regurgitation was more pronounced for the mitral position. A
      total of 261 (29.5%) patients underwent concomitant procedures. Mean follow up is
      2.7 +/- 1.2 years; total follow up is 2386.1 patient-years (pt-yr). RESULTS:
      Total operative (< or = 30 days postoperative) mortality rate was 3.7%; seven
      patients (0.8%) died due to valve-related causes. Total postoperative (> 30 days
      postoperative) mortality rate was 2.5%/pt-yr and included a valve-related
      mortality rate of 1.1%/pt-yr. The following valve-related complication rates
      (%/pt-yr) were reported for the long-term postoperative period: thromboembolism
      0.6; valve thrombosis 0.3; bleeding events 1.5; non-structural deterioration 0.6;
      and endocarditis 0.4. No structural valve deterioration was reported. Actuarial
      freedom at four years was: overall survival rate 86.9 +/- 1.4%; valve-related
      survival rate 94.7 +/- 1.0%; freedom from thromboembolism 96.8 +/- 0.9%; valve
      thrombosis 99.3 +/- 0.3%; endocarditis 98.5 +/- 0.5%; bleeding events 94.3 +/-
      1.0%; and non-structural deterioration 98.2 +/- 0.6%. CONCLUSIONS: The data
      indicate that observed mortality is due mainly to non-valve-related disorders.
      Risk of thromboembolic and bleeding events was low (0.9%/pt-yr and 1.5%/pt-yr,
      respectively). We conclude that this valve is safe and efficacious for use.

PMID- 9587866
TI  - Experience with homograft mitral valve replacement.
AB  - BACKGROUND AND AIMS OF THE STUDY: Homograft mitral valve replacement may offer a
      superior alternative to replacement with a prosthetic valve. The authors' early
      experience with this technique is reported. METHODS: Between May 1994 and May
      1995, 24 patients (19 males, five females; age range 17 to 49 years) underwent
      homograft mitral valve replacement (HMVR) at the authors' institution. The
      etiology was rheumatic in all patients; 22 had severe calcific mitral stenosis
      (MS) and two had combined MS and severe mitral regurgitation (MR). RESULTS: There
      were three early deaths (12%) and two late deaths (8%). In three patients the
      homograft had to be explanted due to severe MR at six weeks, 10 weeks and 12
      months, respectively. Mean follow up was 18 months (range: 12 to 25 months).
      Postoperative echocardiography showed trivial or mild MR in 12 patients and
      moderate MR in four. Mitral stenosis was absent in all patients (mean mitral
      valve area 2.5 cm2). Sixteen patients showed satisfactory homograft valve
      function at follow up. The valve explanted after six weeks showed normal cusp
      architecture, endothelial growth and incorporation of the pericardial strip and
      complete healing of the papillary muscle junction. Magnetic resonance imaging in
      12 patients showed normal appearance and function of the homografts. CONCLUSIONS:
      The authors' experience suggests that homograft mitral valve replacement can be
      performed with good early results.

PMID- 9587867
TI  - Acidic glycoproteins accumulate in calcified areas of bioprosthetic tissue.
AB  - BACKGROUND AND AIMS OF THE STUDY: This study was performed to evaluate the role
      of collagen fibrils, cellular elements and matrix proteins in calcification of
      glutaraldehyde (GA)-fixed bioprosthetic material. METHODS: Lyoplant (lyophilized
      bovine pericardium, type I collagen) was processed according to three protocols.
      DF-group (double fixation): after conventional fixation in GA (0.5% for 72 h;
      storage 0.25%) Lyoplant was implanted subcutaneously into rats for 5 days.
      Specimens were explanted and re-fixed (conventional fixation), followed by
      autologous or homologous reimplantation in rats for 21 or 63 days. CF-group
      (conventional fixation): Lyoplant patches were conventionally fixed (as DF
      group), kept in 0.9% saline for one week, and then autologously and homologously
      reimplanted. GF-group (high-concentration GA): Lyoplant patches were processed
      (as GF-group) but 0.5% GA was used for tissue storage. Explanted specimens were
      studied by light microscopic histochemistry; calcium contents were measured by
      atomic absorption spectroscopy. RESULTS: Severe calcification occurred in the DF
      group without differences between autologous and homologous reimplantation. In CF
      and GF-groups, calcification was negligible, but immunologic response against
      homologous implants was accompanied by increased calcium content. Histologic
      characterization of matrix material in calcified areas revealed oxyphilic
      glycoproteins, identified as sialoglycans. CONCLUSIONS: Modification of
      extracellular matrix by GA is assumed as essential to cause calcification of
      bioprosthetic material. Calcium deposition and accumulation of sialoglycans are
      simultaneous events. A specific role of this glycoprotein for calcification has
      to be considered.

PMID- 9587868
TI  - Repair of fungal aortic prosthetic valve endocarditis associated with periannular
      abscess.
AB  - The incidence of prosthetic valve endocarditis is 2-4%; in most cases the
      involved organisms are Staphylococcus epidermidis and Staph. aureus. Fungal
      endocarditis is much less common (incidence < 0.1%), but it is often fatal, with
      a long-term mortality rate of 90-100%. Most fungal endocarditis cases occur after
      aortic valvular surgery, due to Candida sp. Late-onset symptoms, long-term
      development and aggressive nature of the fungus makes its eradication complicated
      and treatment difficult. Fungal valvular mycoses produce systemic embolization
      and cause serious perioperative bleeding on resection of infected tissue. Usually
      surgery includes aortic root replacement with an aortic homograft conduit after
      radical debridement, to attain local sterilization. This report describes a
      patient with complex infection, requiring replacement of an infected prosthetic
      valve with an aortic homograft conduit, aggressive and radical debridement of
      infected tissue, and reconstruction using biologic tissues. The case demonstrates
      the importance of perioperative and long-term antifungal treatment and presents a
      modified 'Cabrol procedure' to prevent critical intraoperative hemorrhage.

PMID- 9587869
TI  - A case report of Candida parapsilosis endocarditis.
AB  - A 57-year-old male was treated for fungal endocarditis caused by Candida
      parapsilosis which precipitated severe cardiac valve vegetation and
      insufficiency. His condition resulted from a three-month installation of a
      central venous catheter for hyperalimentation and chemotherapy following total
      gastrectomy for gastric cancer. Aortic valve replacement combined with
      fluconazole administration resulted in satisfactory recovery with no adverse
      events during an 18-month follow up period.

PMID- 9587870
TI  - Kinetics and energetics of specific intermolecular interactions.
AB  - Taking into account the energy vs. distance functions of the aspecific
      (macroscopic) repulsion that usually prevails between antigen (Ag) and antibody
      (Ab) molecules in polar media, as well as the specific (microscopic) attraction
      between epitope and paratope of Ag and Ab, it proved possible to determine the
      kinetic constants (von Smoluchowski, 1917; Hammes, 1978) of Ag-Ab interactions,
      from the surface properties of Ag, Ab and the aqueous medium. The kinetic
      constants thus found correlate well with experimentally determined kinetic
      constants in comparable systems, and confirm the importance of the influence of
      the concentration of one of the reagents (e.g. the Ab) on the kinetic association
      constant (Van Regenmortel et al., 1994), which is largely due to steric
      hindrance. Applying the same energy vs. distance approach to the influence of
      temperature (T) on Ag-Ab reactions, it ensues that the familiar occurrence of an
      apparent 'enthalpy-entropy compensation' in aqueous media is in fact the
      relatively gratuitous outcome of a complex set of effects caused by an increase
      in T, on the total free energy, the hydration energy and, as a result, on the
      inter-epitope-paratope distance. A close correlation exists between the outcome
      of these surface-thermodynamic analyses and experimental results.

PMID- 9587871
TI  - Screening of a small set of random peptides: a new strategy to identify synthetic
      peptides that mimic epitopes.
AB  - Small diversity libraries, composed of 4550 synthetic dodecapeptides and 8000
      synthetic tripeptides, have been used to identify sequences homologous to small
      linear and non-linear parts of epitopes. Here we report that synthetic peptides
      identified through alignment of dodecapeptides and tripeptides derived from these
      small libraries have, in direct ELISA and/or competitive ELISA, activities
      similar to that of peptides covering the native epitope and similar to that of
      peptides derived from large expression libraries composed of 10(6)-10(7) random
      peptides. This result was obtained with the monoclonal antibodies 6A.A6 and M2.
      Mab 6A.A6 binds the transmissible gastroenteritis virus (TGEV) and mAb M2 binds
      the FLAG-peptide, an affinity tag. It was also found that the antibody binding
      activity of peptides, derived from small or large libraries, can strongly depend
      on the way in which the peptide is presented to the antibody, i.e. high antibody
      titers were obtained when these peptides were synthesized on pins or coated onto
      microtiter plates, whereas low IC50s were obtained with these peptides in
      solution. We postulate that small peptide libraries may be a powerful tool to
      quickly identify new peptides that can be used as sensitive markers for mAbs of
      interest.

PMID- 9587872
TI  - Dual specificity and the formation of stable autoimmune complexes.
AB  - Since dual specificity at the antibody active-site level involves new principles
      relative to monospecific antigen-antibody interactions and may be a general
      property of autoantibodies, it was important to further characterize such
      antibodies. Four lupus derived autoantibodies were studied to understand
      parameters and mechanisms involved in the participation of dual-specific antibody
      molecules in the formation of highly stable immune complexes. Because the dual
      specific binding properties of selected lupus-related murine autoantibodies had
      been previously described using a solid-phase polystyrene-based ELISA, a
      conformational sensitive membrane based assay (CSI) was used on a comparative
      basis to further characterize NZB/NZW F1 murine monoclonal anti-DNA
      autoantibodies BV 04-01 (anti-ssDNA), BV 16-19 (anti-ssDNA), BV 17-45 (anti
      dsDNA), and BV 16-13 (anti-dsDNA). All four monoclonal autoantibodies exhibited
      anti-IgG binding in the solid-phase ELISA. However in the CSI assay, only anti
      dsDNA monoclonal autoantibodies BV 17-45 and BV 16-13 demonstrated anti-IgG
      binding, while anti-ssDNA autoantibodies BV 04-01 and BV 16-19 did not. Upon
      subjection to time-dependent thermal denaturation, with and without thiol
      reduction at 100 degrees C in the CSI, the self-binding activities of BV 17-45
      and BV 16-13 were abrogated demonstrating that the recognized IgG autoepitope(s)
      possessed conformational or discontinuous three-dimensional properties. The
      immunological implications of dual specificity are discussed on a structure
      function basis and its correlation with formation of pathogenic immune complexes.

PMID- 9587873
TI  - Recognition of superpotent sweetener ligands by a library of monoclonal
      antibodies.
AB  - Monoclonal antibodies (mAb) made to the superpotent guanidino sweet tasting
      ligand, N-(p-cyanophenyl)-N'-(diphenylmethyl)-guanidineacetic acid were examined
      for their molecular recognition specificities using 14 different sweetener
      analogues in a competitive radioimmunoassay. The effects of variations in pH on
      ligand binding was also examined by radioimmunoassay. Photoaffinity labelling of
      the binding site was accomplished using a radiolabelled azido-derivative of the
      parent ligand, and L-chain or H-chain labelling was easily identified in several
      different mAb. For two of the mAb examined in this study (NC6.8 and NC10.14), the
      analogue binding studies are in agreement with the known Fab-ligand crystal
      structures. Monoclonal antibodies to this family of sweet tasting compounds may
      be useful probes for the study of sweet taste chemistry and identification of
      novel sweet taste ligands from combinatorial chemical libraries.

PMID- 9587874
TI  - Current issues in eating disorders research.

PMID- 9587875
TI  - Potential risk factors associated with weight control behaviors in elementary and
      middle school girls.
AB  - The purpose of this study was to examine the relationship between weight control
      behaviors and potential risk factors for disordered eating in a sample of young
      girls. The McKnight Risk Factor Survey was administered to 523 elementary and
      middle school girls. In the sample of elementary school girls, results from the
      multiple regression analyses indicated that frequency/severity of weight control
      behaviors was associated with body mass index (BMI), self-confidence, peers'
      weight-related pressures, ethnicity, and the interaction between having
      divorced/separated parents and BMI. Sensitivity to peers' weight-related
      pressures and BMI were also associated with weight control behaviors in the
      middle school girls, along with poor body image, substance use, having
      divorced/separated parents, and the interaction between having divorced/separated
      parents and father's pressure for thinness. Longitudinal research is needed to
      determine how risk factors change over time, beginning in elementary school and
      continuing through high school.

PMID- 9587876
TI  - An evaluation of a structural model for studies of the initiation of dieting
      among adolescent girls.
AB  - A model proposed to elucidate the sociopsychological processes involved in the
      initiation of dieting behavior among female adolescents was evaluated in the
      present study. The model incorporates social influence (as modeling, conformity,
      and compliance), autonomous functioning (as conformity disposition,
      individuation, self-reliance, and locus of control), skill-related functioning
      (as interpersonal negotiation skills and social self-efficacy), and parental
      style (in care and overprotection). It was investigated using path analytic
      procedures. One hundred forty-eight female high school students, aged between 13
      and 16 years, completed a battery of questionnaires and were also interviewed
      individually. The results emphasized that adolescent dieting needs to be
      understood as a complex multicausal phenomenon. Adolescents' perceptions of
      direct pressure from their parents to diet was found to be a significant
      predictor of dieting, and perceived parental encouragement of autonomy, and self
      confidence were associated with less dieting behavior. Moreover, whereas body
      mass index (BMI) and body dissatisfaction significantly predicted dieting, the
      three sociopsychological variables remained significant predictors of dieting
      when taking BMI into account, and perceived parent influence to diet remained a
      significant predictor when taking body dissatisfaction into account. The effect
      of autonomous functioning on dieting was mediated by body dissatisfaction. The
      findings suggest a reformulated model for use in large-scale longitudinal
      investigations.

PMID- 9587877
TI  - Disordered eating, weight dissatisfaction and dieting in relation to unwanted
      childhood sexual experiences in a community sample.
AB  - A study was conducted to examine the relationships among eating pathology, weight
      dissatisfaction and dieting, and unwanted sexual experiences in childhood. An
      unselected community sample of 201 young and 268 middle-aged women were
      administered questionnaires assessing eating behaviors and attitudes, and past
      and current sexual abuse. Results showed differential relationships among these
      factors for the two age cohorts: for young women, past sexual abuse predicted
      weight dissatisfaction, but not dieting or disordered eating behaviors, whereas
      for middle-aged women, past abuse was predictive of disordered eating, but not
      dieting or weight dissatisfaction. Current physical or sexual abuse was also
      found to be predictive of disordered eating for the young women. These findings
      underscore the complexity of the relationships among unwanted sexual experiences
      and eating and weight pathology, and suggest that the timing of sexual abuse, and
      the age of the woman, are important mediating factors.

PMID- 9587878
TI  - A controlled evaluation of an elementary school primary prevention program for
      eating problems.
AB  - Researchers have recently called for the development of primary prevention of
      eating disorders programs aimed at elementary school students. The present study
      reports on the development of a curriculum for fifth graders designed to
      encourage healthy eating, exercise, and body image while discouraging calorie
      restrictive dieting, exercising for weight loss, and the development of body
      dissatisfaction. The program consisted of ten lessons taught by the classroom
      teachers. The influence of the curriculum on (1) knowledge about nutrition, body
      fat, and dieting; (2) attitudes about fat people and own body (body esteem); and
      (3) behaviors, including attempts at weight reduction, consumption of fruits and
      vegetables, and exercising, were evaluated in a pre-post controlled experimental
      design. There were 222 white public school children who participated in both the
      pre- and posttesting, 167 of whom were in the classrooms receiving the
      curriculum. Results indicated that knowledge was broadly improved by the
      curriculum. There were information improvements in terms of nutrition, effects of
      dieting, and causes of body fat. Attitudinal changes were less pronounced,
      although the curriculum did positively affect attitudes about fat people.
      Behavior, including eating patterns, exercise patterns, weight reduction
      attempts, and teasing of fat children, was not changed by participation in the
      curriculum.

PMID- 9587879
TI  - Intimacy patterns and relationship satisfaction of women with eating problems and
      the mediating effects of depression, trait anxiety and social anxiety.
AB  - The association between eating problems; and intimacy and relationship styles was
      examined. Young adult females (n = 360) completed the Adult Attachment Style
      (AAS), questionnaire; questions on satisfaction with intimacy; the Sexual
      Attitude Scale; items on sexual avoidance; a set of six descriptions for mother,
      friend, and partner; and measures of depression, general anxiety, social anxiety,
      and eating problems. Women with greater eating problems described more
      difficulties in intimate relationships including less satisfaction with
      closeness, more discomfort in close intimate relationships, and less positive
      descriptions of friend and mother. When depression, general anxiety, and social
      anxiety were entered first in a regression, intimacy measures no longer added
      unique variance. However, public self-consciousness predicted over and above
      general affect and social anxiety measures. Results were consistent with a
      mediator model in which intimacy difficulties for women with eating problems are
      explained by depression, trait anxiety, and public self-consciousness.

PMID- 9587880
TI  - Onset of binge eating and dieting in overweight women: implications for etiology,
      associated features and treatment.
AB  - This study investigated differences between overweight binge eating women who
      reported the onset of binge eating prior to or following the onset of dieting
      (binged first [BF], or dieted first [DF]). Of overweight binge eating subjects
      enrolled in a treatment study, 38.7% indicated binge eating first, and 48.1%
      dieting first. The mean age of onset of binge eating differed significantly
      between the two groups (11.8 years vs. 25.7 years). More of the BF group (82.5%)
      satisfied proposed binge eating disorder (BED) criteria than did the DF group
      (52.0%), although short of significantly. The results suggest that: (a) the
      leading hypothesis concerning dieting as a cause of binge eating does not apply
      to a substantial number of individuals who binge eat; (b) there may be an early
      pattern and a late pattern in the development of binge eating among overweight
      individuals; and (c) the early or binge first pattern may be more likely to
      result in BED.

PMID- 9587881
TI  - Behavioral treatment of obese binge eaters: do they need different care?
AB  - This study investigated the relationship between binge eating and the outcome of
      weight loss treatment. Participants in a 48-week trial of a structured diet
      combined with exercise and behavior therapy were classified into one of four
      groups: no overeating; episodic overeating; subthreshold binge-eating
      disorder(BED); and BED. Binge eating status was not associated with either
      dropout or adherence to the diet, but did affect weight loss and mood. The BED
      group lost significantly more weight at the end of treatment than all other
      groups, even when adjusting for initial weight. At 1-year follow-up, there were
      no differences among groups in weight loss or weight regain. The BED group began
      treatment with significantly higher BDI scores, but improvement in mood occurred
      by week 5. On the basis of these findings, and a review of the recent literature,
      we conclude that obese binge eaters respond as favorably to standard dietary and
      behavioral treatments as do obese nonbingers.

PMID- 9587882
TI  - Binge eating disorder: treatment outcome over a 6-year course.
AB  - Little is known about the long-term course of binge eating disorder (BED). The
      aim of the study was to assess the 3- and 6-year course and outcome of 68
      consecutively treated females with BED. Their mean age was 29.3 years and they
      were assessed longitudinally at four timepoints: (1) beginning of therapy; (2)
      end of therapy; (3) 3-year follow-up; and (4) 6-year follow-up. Self rating as
      well as expert ratings were used for assessment. Symptoms of specific eating
      disorder as well as general psychopathology were measured. The general pattern of
      results over time was as follows: substantial improvement during therapy; slight
      (in most cases nonsignificant) decline during the first 3 years after the end of
      treatment, and further improvement and stabilization in years 4, 5, and 6 after
      the end of treatment. At the 6-year follow-up, the majority showed no major DSM
      IV eating disorder, 5.9% had BED, 7.4% had shifted to bulimia nervosa (purging
      type) (DSM-IV), 7.4% were classified as ED-NOS, and one patient died. Based on an
      operationalized global outcome score for the complete sample, 57.4% had good
      outcome, 35.3% intermediate outcome, 5.9% poor outcome, and one person (1.4%)
      died. BED and BNP patients showed very similar intermediate and long-term course
      in self ratings as well as expert ratings.

PMID- 9587883
TI  - Participant reactions to a cognitive-behavioral guided self-help program for
      binge eating: developing criteria for program evaluation.
AB  - This article evaluates the effectiveness of a telephone-based guided self-help
      program for women who binge eat. We report how key program components (e.g.,
      phone sessions, the self-help book) contribute to the four self-help goals
      identified in the clinical literature: (1) decrease isolation/increase support;
      (2) increase knowledge of the problem; (3) broaden coping skills; and (4) improve
      self-esteem. Using the example of our feasibility study, we illustrate that even
      minimal interventions create a relational context which can promote entry into
      and engagement with treatment. We conclude that program evaluation should include
      not only traditional measures of outcome (e.g., reduction in symptomatology), but
      utilize outcome measures related to the specific goals of minimal interventions
      (e.g., changes in help-seeking behavior).

PMID- 9587884
TI  - Standardized mortality in eating disorders--a quantitative summary of previously
      published and new evidence.
AB  - Ten eating disorder (ED) populations were reviewed using the standardized
      mortality ratio (SMR) presenting new evidence for several studies. In eight of
      the ten samples, strong evidence (in one sample weak evidence and in one sample
      no evidence) supports an hypothesis of elevated SMR. We found strong evidence for
      an increase in SMR for anorexia nervosa (AN), whereas no firm conclusions could
      be drawn for bulimia nervosa (BN). Bias caused by loss to follow-up was
      quantified and found non-negligable in some samples (possible increase in SMR
      from 25% to 240%). We did not find a significant effect of gender or time period
      on SMR. Survival analysis showed a significant difference among the life-tables
      for males and females; female risk of death averaged 0.59% per year, whereas all
      male deaths occurred within the first 2 years after presentation. Weight at
      presentation had a highly significant effect on SMR, and lower weight at
      presentation was associated with higher SMR. Age at presentation exerted a
      significant unimodal effect on SMR; aggregate overall SMR was 3.6 for the
      youngest age group (< 20 years), 9.9 for those aged 20-29 years, and 5.7 for
      those aged > or = 30 years at presentation. Length of follow-up had a highly
      significant inverse effect on SMR; maximal SMR was 30 for female AN patients in
      the first year after presentation. A statistically significant increase in SMR
      was documented for at least up to 15 years after presentation. One study
      indicated a treatment effect on SMR. New evidence on causes of death suggests
      there are more deaths from suicide and other and unknown causes and fewer deaths
      related to ED than previously reported. Our findings have both research and
      clinical implications, with the most important clinical implication being the
      need for vigorous and well-directed treatment efforts from the initial
      presentation for treatment. An important research implication is that no single
      measure of mortality is sufficient; that is, only a combination of different
      statistics will maximize the available information.

PMID- 9587885
TI  - Is amenorrhea a critical criterion for anorexia nervosa?
AB  - The significance of amenorrhea as a criterion for anorexia nervosa was examined.
      Twelve nonamenorrheic women treated for anorexia were compared with 40 women
      meeting full DSM-IV criteria. The nonamenorrheic group displayed the same high
      levels of eating disorder, body-image disturbance, and psychopathology as the
      amenorrheic group, as measured by the following variables: body-size
      overestimation on the Image Marking Procedure; body distortion on the Body
      Distortion Questionnaire; eating disorder on the Eating Disorder Inventory;
      depression on the Beck Depression Inventory; psychopathology on the MMPI; and
      external locus of control on the Rotter Locus of Control Scale. Amenorrhea does
      not appear to be a useful criterion for distinguishing full-syndrome anorexia
      nervosa from partial-syndrome cases.

PMID- 9587886
TI  - A comparison of eating disorders and body dysmorphic disorder on body image and
      psychological adjustment.
AB  - Eating and body dysmorphic disorders are two diagnoses with body image
      disturbance as a central feature. No empirical study of the similarity of these
      disorders or any controlled study of body dysmorphic disorder were available. The
      present study compared 45 women with anorexia or bulimia nervosa to 51 men and
      women with body dysmorphic disorder (BDD) and 50 nonclinical controls. The eating
      disorder patients were mainly preoccupied with weight and body shape. BDD
      subjects had more diverse physical complaints and reported more negative self
      evaluation and avoidance due to appearance. However, the two groups showed
      equally severe body image symptoms overall, and were clearly abnormal compared
      with controls. Both types of patients had negative self-esteem, but eating
      disorder patients had more widespread psychological symptoms. In conclusion, the
      disorders are comparable on psychological measures. Explanations of the minor
      differences and questions for future research on the relation between eating and
      body dysmorphic disorders are presented.

PMID- 9587887
TI  - Body size estimation in anorexia nervosa patients: the significance of
      overestimation.
AB  - Using the video distortion method on a life-size screen, we have studied body
      size estimation in 100 female restricting anorexia nervosa patients. About half
      of the patients were accurate in estimating their own body dimensions and only
      20% clearly showed overestimation. We then tested whether differences in accuracy
      of estimation were related to scores on the following questionnaires: Eating
      Disorder Inventory; Body Attitude Test; and Symptom Checklist (SCL-90).
      Overestimators reported a more negative body attitude and a more "neurotic
      profile" on the SCL-90. These differences might have both prognostic and
      therapeutic implications.

PMID- 9587888
TI  - Body perception index: benefits, pitfalls, ideas.
AB  - Estimates of body size are often expressed as a ratio of actual size [body
      perception index or BPI = (estimated size/actual size) x 100%]. In this article,
      we examine the possibility that overestimation of body size in patients with
      anorexia nervosa, as measured by the BPI, is due to their smaller body size
      rather than to their being anorexic. Using 50 mean body sizes derived from seven
      studies we investigated whether the error of estimation is a constant proportion
      of the body size to be estimated, as the use of the BPI assumes. A negative
      linear relation between BPI and actual body size was found, confirming that
      smaller size is associated with greater overestimation. However, although both
      groups showed a strong tendency to overestimate smaller sizes, anorexic subjects
      showed even greater overestimation than controls. Hence, overestimation of body
      size in AN can only partially be accounted for by the smaller body size of
      anorexic patients. Recommendations for future use of the BPI are put forward.

PMID- 9587889
TI  - Eating behavior and pregnancy outcome.
AB  - The association between clinical eating disorders, maternal body weight, shape,
      and eating concerns, and the birth of low-birth-weight infants (LBW; less than
      2500 g) was investigated using a retrospective case-control study. Eighty-eight
      women delivering LBW infants were interviewed and then divided into two groups-
      those delivering term, small-for-gestational-age infants (SGA; 37 or more
      completed weeks, n = 34) and those delivering premature infants (less than 37
      completed weeks, n = 54). There were 86 reference women (CTRL) matched for age,
      parity, and health insurance status, who delivered babies with birth weights
      greater than 2500 g. In the week postpartum, women delivering term SGA, premature
      (PREM), and CTRL infants were interviewed using a semistructured interview. One
      section of this interview included a modified version of the Eating Disorder
      Examination (EDE), which retrospectively generated, over the previous 12 months,
      diagnosis of an eating disorder and maternal "normative" weight and shape
      concerns. In the 3 months before pregnancy, 32% of SGA women, 9% PREM women, and
      5% of reference women were diagnosed as having a clinical eating disorder. Women
      with a past history of an eating disorder had no greater risk of delivering a low
      birth-weight infant. Women delivering SGA infants, reported elevated eating
      disorder psychopathology postdelivery (Eating Disorders Inventory, EDI) and more
      disturbances in eating behavior before and during pregnancy. Unique predictors
      for delivery of a LBW term SGA infant were: low maternal prepregnancy body
      weight, smoking, low maternal weekly weight gain, and elevated EDI (Bulimia
      subscale). Unique predictors for delivery of a LBW premature infant were: lower
      maternal occupational status, vomiting in pregnancy, and lower dietary restraint.
      Women with disordered eating were shown to be at greater risk of delivering term
      SGA infants. Predictors of term growth retardation are partly determined by
      maternal behavior.

PMID- 9587890
TI  - Eating disturbances, diabetes and the family: an empirical study.
AB  - This study of 113 adolescent females with IDDM and their mothers investigated
      whether: (1) interaction patterns are more dysfunctional in families of girls
      with eating disturbances than in those without; and (2) the relationship between
      family functioning and metabolic control is mediated by an eating disturbance.
      Based on self-reported eating attitudes and behaviors, subjects were categorized
      as Nondisturbed (N = 56), Mildly Disturbed (N = 37), and Highly Disturbed (N =
      20). Mothers and daughters rated overall family functioning (FES), and daughters
      rated parental relationships (IPPA, MFP). Metabolic control was assessed using
      HbA1c levels. MANCOVA illustrated that eating disturbances are associated with
      the perception of poor communication with mothers and fathers, a lack of trust in
      their accessibility and responsiveness, and overall family environments perceived
      to be conflictual and inadequate in support and structure. Regression analyses
      revealed that the presence and severity of an eating disturbance mediates the
      influence of family functioning on metabolic control.

PMID- 9587891
TI  - Sexuality and reproduction in bulimia nervosa patients over 10 years.
AB  - The reproductive and sexual histories of women who had recovered or were
      recovering from bulimia nervosa were examined. Of 48 consecutive female patients,
      43 were studied 10-15 years after first presenting for treatment. At follow-up,
      74% were considered recovered and 26% still had an eating disorder. Only 2 women
      fulfilled the criteria for bulimia nervosa. A history of amenorrhea was common
      (81% of women), 63% of women being without their menstrual periods for more than
      12 months. Menstruation was present in women at a body mass index of 19 or more
      who were no longer using the weight loss practices of self-induced vomiting,
      laxative abuse, and starvation. Bulimia nervosa women are more likely to be
      investigated for infertility when their eating disorder is active. Bulimia
      sufferers are sexually active, but have times of withdrawing from their partners
      and ceasing sexual behavior. They associate their sexual feeling with body
      weight, pregnancy, breastfeeding, and status of their relationships. Marital
      breakdown is also more common but only if the eating disorder was active at the
      time of marriage. Forty-five percent left their relationship had a negative
      effect on their eating disorder. Short-term episodes of bulimic-free behavior are
      associated with pregnancy and breastfeeding in some pregnancies. Termination of
      pregnancy occurs more often. The prevalence of miscarriage, hyperemesis
      gravidarum, and postnatal depression was greater among women who had not
      recovered from their eating disorder at the time of their pregnancy. Recovery
      from eating disorder behavior before attempting conception reduces the prevalence
      of the gynecologic, obstetric, and psychiatric problems associated with eating
      disorder behavior.

PMID- 9587892
TI  - Diabetes mellitus and eating disorders: a multicenter study on the comorbidity of
      the two diseases.
AB  - Because diet is a key issue in the treatment of diabetes mellitus, it is assumed
      that these patients are prone to eating disorders. In a multicenter study, we
      have therefore assessed the prevalence of eating disorders in 662 patients with
      insulin dependent diabetes mellitus (IDDM) (n = 340) and non-insulin-dependent
      diabetes mellitus (NIDDM) (n = 322). A two-stage study combining self-rating
      questionnaires and a standardized interview was carried out. We found a
      prevalence of eating disorders of 5.9% (lifetime prevalence of 10%), irrespective
      of gender and type of diabetes; 4.1% of the whole sample reported intentional
      insulin undertreatment or omission. When patients were stratified according to
      IDDM and NIDDM, there was no difference in the prevalence of all eating disorders
      (point prevalence 5.5% vs. 6.5%, lifetime prevalence 10.0% vs. 9.9%). Prevalence
      of bulimia nervosa (BN) was more frequent in IDDM patients (point prevalence 1.5%
      vs. 0.3%, lifetime prevalence 3.2% vs. 1.9%) and binge eating (BED) was more
      frequent in NIDDM patients (point prevalence 1.8% vs. 3.7%, lifetime prevalence
      2.6% vs. 5.9%). We conclude that eating disorders seem to be equally frequent in
      IDDM and NIDDM patients. However, there might be different features of eating
      disorders in both types of diabetes.

PMID- 9587893
TI  - Advances in cubicle design using computational fluid dynamics as a design tool.
AB  - As part of a recent animal facility refurbishment, a cubicle containment system
      was designed to increase the amount of experimental space and also provide
      containment facilities to support the holding and use of specialized animal
      models. In order to achieve this, a series of computational fluid dynamic (CFD)
      studies was undertaken to evaluate the effects of different airflows and in order
      to optimize ventilation, a variety of exhaust/supply arrangements and animal
      loads was employed. These studies showed that air delivered via two, opposed, low
      level ducts, at a rate of 20 air changes per hour and exhausted high in the
      cubicle above the rack, was the optimal configuration resulting in minimal
      turbulence, stagnation and entrainment.

PMID- 9587894
TI  - Ethics training for laboratory animal users.
AB  - In the UK, all applicants for licences under the Animals (Scientific Procedures)
      Act 1986 must receive training in ethical aspects of laboratory animal use. There
      is, however, considerable uncertainty about the aims, suitable content and most
      appropriate means of delivery of such training. In this review a series of aims
      for licensee training in ethics are proposed, the key content is described and
      possible approaches to delivering such training are critically evaluated. Ethics
      training, it is argued, should: (i) be rooted in practice, focusing on the
      practical application of the Act to licensees' own work and encouraging them to
      take all possible steps to reduce or resolve any moral conflicts which the work
      entails; (ii) promote discussion, encouraging licensees to challenge their own
      views and critically appraise their work; and (iii) provide the necessary
      theoretical background to inform and stimulate such discussion. A variety of
      means of generating discussion and a range of practical considerations are
      explored.

PMID- 9587895
TI  - Advancing refinement of laboratory animal use.
AB  - Whatever view is taken of the morality of using animals in scientific research
      and safety testing, it can generally be agreed that so long as such use
      continues, every effort should be made to keep animal suffering to a minimum.
      This is the thinking behind the 'Three Rs' of refinement, reduction and
      replacement of laboratory animal use. This paper concerns refinement. We
      recognize that the Three Rs are taken very seriously in many countries of the
      world [see for example a recent editorial in the journal Science (Goldberg et al.
      1996)] and, although we have written this paper from our own perspective in the
      UK, its principles are generally applicable.

PMID- 9587896
TI  - Comparison of effects of restraint, cage transportation, anaesthesia and repeated
      bleeding on plasma glucose levels between mice and rats.
AB  - We examined the effects of handling, cage transportation, anaesthesia and
      repeated bleeding on plasma glucose levels in mice and rats. Plasma glucose was
      determined using a compact glucose analyser Antsense, which provides a quick and
      accurate method without the necessity for special specimen preparation. In mice,
      plasma glucose was significantly elevated after primary handling or cage
      transportation. Anaesthesia increased plasma glucose levels two-fold, whilst
      repeated bleeding induced a rapid but transient increase. However, it was found
      to be possible to sample plasma glucose levels at one-hour intervals without any
      apparent effect on plasma glucose level as a result of stress from the sampling
      procedure. In contrast, the same set of procedures i.e. handling, cage
      transportation and anaesthesia, when performed on rats, seemed to have small or
      no observable effect on levels of plasma glucose. These results show the
      importance of the sampling procedure when determining plasma glucose in mice. It
      is recommended that the procedure which causes the least influence on endogenous
      glucose levels should be the method of choice and that animals should be
      acclimatized to the procedure, by appropriate handling, prior to sampling.

PMID- 9587898
TI  - Oral endotrachael intubation of guineapigs.
AB  - Oral endotracheal intubation of guineapigs as reported in the literature, is
      considered to be extremely difficult. Because of this, we constructed special
      equipment and developed a technique to facilitate the procedure. A special
      restraint device was designed to position the guineapig. Utilizing a laryngoscope
      and an operating microscope for visualization then makes intubation easy to
      perform.

PMID- 9587897
TI  - Influence of oral buprenorphine, oral naltrexone or morphine on the effects of
      laparotomy in the rat.
AB  - The effects of oral administration of buprenorphine ('buprenorphine jello'), a
      partial mu opioid agonist, oral naltrexone, a mu antagonist and morphine, a mu
      agonist, were investigated in rats following laparotomy. Food and water
      consumption and body weight were reduced in rats that underwent surgery. Rats
      undergoing anaesthesia alone showed only a small reduction in water consumption.
      Administration of oral buprenorphine (0.5 mg/kg in flavoured gelatin) decreased
      the effects of surgery on body weight and water intake when compared to untreated
      (vehicle alone) controls. The magnitude of this beneficial effect was similar to
      that seen in previous studies using subcutaneous administration of buprenorphine.
      The fall in body weight and food and water intake following surgery was similar
      in the groups which received morphine and the control group which received
      vehicle (jelly). Neither the magnitude of the fall in body weight, and food and
      water intake, nor the behavioural scores differed between naltrexone and control
      (vehicle alone) rats following surgery. This suggests that the beneficial effects
      of partial agonist analgesics are mediated by a reduction in pain rather than by
      antagonism of endogenous opioids. Both anaesthesia and surgery caused changes in
      behaviour, but the major effects of buprenorphine in normal (unoperated) rats
      severely limited the value of behavioural parameters as a means of assessing
      possible beneficial effects of analgesic administration.

PMID- 9587899
TI  - Establishment of a 24-hour electrocardiogram recording system using a Holter
      recorder for miniature swine.
AB  - A Holter recording system was established for the Gottingen miniature swine. For
      this purpose, we first developed a jacket to hold a Holter recording set, and
      subsequently determined a bipolar lead suitable for obtaining stable
      electrocardiogram (ECG) recording without artifacts. To make the jacket, we
      measured the lengths of eight sites of the body of 14 miniature swine. Several
      types of jackets were made and tested. We observed the behaviour of animals with
      these jackets by videotape recorder (VTR) recording. These observations permitted
      development of a jacket suitable for Holter recording. The jacket permits easy
      placement of the recorder, and long-term ECG recording can be performed without
      difficulty. In order to determine a suitable lead for long-term recording, we
      recorded ECGs from six adult miniature swine using three types of leads, the M-X,
      R-L and A-B leads. The R-L lead frequently exhibited baseline drift, and QRS
      complexes often disappeared in this lead due to low amplitude. ECG recording with
      the M-X and A-B leads was of sufficient quality to permit analysis. This system
      is expected to be useful for further cardiovascular research in miniature swine.

PMID- 9587900
TI  - Echocardiography, a non-invasive method for the investigation of heart morphology
      and function in laboratory dogs: 1. Method and reference values for M-mode
      parameters.
AB  - We have set up M-mode echocardiographic (EC) recording in beagles in our
      laboratory and generated reference values for EC indicators of left ventricle
      function and morphology. Additionally we assessed the effects of sex, strain and
      body weight on these parameters and the correlation between parameters. M-mode EC
      under two-dimensional guidance in longitudinal section was performed on 59 male
      and 49 female beagles from Marshall (USA) and 13 males and 13 females from Harlan
      (France). The following parameters were measured or calculated: left ventricle
      internal diameter in diastole and systole (LVIDd and LVIDs), left ventricle and
      diastolic and end systolic and stroke volumes (EDV, ESV and SV), cardiac output
      and index (CO and CI), fractional shortening (FS), ejection fraction (EF), the
      thickness of the septum and left ventricle posterior wall in diastole (STd and
      LVPWd) and systole (STs and LVPWs), the percentage of thickening of the septum
      and left posterior wall (PST and PWT), and the mean and maximal velocities of the
      left ventricle posterior wall (PWVm and PWVM). Heart rate (HR) was measured by
      cardiac auscultation. Marshall dogs have higher left ventricle dimensions but
      lower amplitude and velocity of contraction than Harlan dogs. There were also
      statistically significant differences between sexes for a number of EC parameters
      mainly those relating to the size of the left ventricle walls or cavity in
      diastole. Overall these differences were explained by the correlation between
      these parameters and body weight. Heart rate correlated only with PWVm and PWVM.
      There were positive correlations between PST, PWT and EF or FS and between
      velocities and FS or EF. EDV correlates negatively with EF, FS, PST or PWT.

PMID- 9587901
TI  - Echocardiography, a non-invasive method for the investigation of heart morphology
      and function in laboratory dogs: 2. Effects of minoxidil and quinidine on the
      left ventricle function.
AB  - We used echocardiography to investigate the changes in the cardiac function of
      dogs treated with minoxidil (a vasodilator, administered at doses which can
      produce mild lesions in the myocardium of the left ventricle) and quinidine (an
      antiarrhythmic at doses up to 8 times the upper limit of the therapeutic range in
      dogs). Groups of three beagles received a single administration of minoxidil at
      doses of 0.5 or 2 mg/kg. Two groups of two dogs received a single administration
      of quinidine at doses of 80 or 160 mg/kg. Two groups of three control dogs were
      treated concurrently with the vehicle alone. M-mode echocardiography was
      performed under two-dimensional echocardiography guidance on three occasions the
      day before treatment, immediately before dosing and 1, 3 and 24 h after dosing.
      We measured or calculated end diastolic, end systolic, and stroke volumes (EDV,
      ESV and SV), fractional shortening (FS), ejection fraction (EF), the percentage
      of thickening of the septum and of the left ventricle posterior wall (PST and
      PWT), and the mean and maximal velocities of the left ventricle posterior wall
      (PWVm and PWVM). At the same time as echocardiography recording, heart rate was
      measured by cardiac auscultation. Minoxidil produced a marked tachycardia. Less
      marked increases in heart rate occurred after quinidine. Both compounds were
      associated with a decrease in ESV and with marked increases in FS, EF, PWVm and
      PWVM which, in comparison with data for controls, are indicative of an increase
      in the amplitude and velocity of cardiac contraction. Both drugs also produced a
      decrease in EDV and consequently there was no increase in SV despite the
      increased amplitude of ventricular contraction. Cardiac output increased in
      proportion to the increase in heart rate. Overall, the effects were dose-related
      and are consistent with the pharmacological properties of the compounds. However,
      to date these effects have been demonstrated only by invasive methods. To
      conclude, we have shown that echocardiography allows a non-invasive investigation
      of the cardiac effects of suprapharmacological doses of antiarrhythmics and of
      the changes in heart function induced by vasodilators known to cause left
      ventricular lesions in dogs.

PMID- 9587902
TI  - Experimental intracoronary stenting: comprehensive experience in a porcine model.
AB  - Appropriate animal models for intracoronary stenting are most important for
      improving understanding of the pathophysiology of acute occlusion and long-term
      re-stenosis, which currently limits the safety and efficacy of percutaneous
      transluminal coronary angioplasty in humans. Since the anatomy and physiology of
      swine coronary arteries closely resemble those of humans, the procine model
      should be ideal for testing of stents. This is a comprehensive report on an
      experimental set-up in pigs, communicating in detail the necessary techniques as
      well as some modifications facilitating safe intracoronary stent placement and
      successful follow-up studies for weeks or months. Stent procedure is performed in
      mechanically ventilated and haemodynamically monitored animals under balanced
      anaesthesia. Intracoronary application of flow wires allows the assessment of
      local flow conditions, flow properties and coronary flow reserve. Real-time
      intravascular ultrasonography (IVUS) provides detailed information on coronary
      morphology and enables the appropriate sizing of the coronary lumen. From our own
      experience, we like to propose that the use of the porcine model has the
      potential to gain new insights into the pathophysiology of intracoronary stent
      placement-associated complications and allows for the study of modifications in
      techniques and materials, and the development of novel pharmacological
      therapeutic strategies.

PMID- 9587903
TI  - Coronary artery distribution in Macaca fascicularis (Cynomolgus).
AB  - The studies were performed using stereomicroscopic dissection, and light
      microscopy examination on hearts of healthy and fertile non-human primates
      (Macaca fascicularis) of both sexes. The results indicate that the anatomy of the
      coronary arteries offers points of similarity as well as departure from humans.
      The blood supply to the hearts was by left (LCA) and right (RCA) coronary
      arteries. The LCA averaged 1.78 +/- 0.29 (SD) mm (range 1.40-2.40 mm) in external
      diameter at its origin, and 4.34 +/- 1.29 (SD) mm (range 1.8-6.5 mm) in length.
      It usually terminated by dividing into a left anterior descending artery (LAD)
      and the circumflex branch (CXA). The CXA branch coursed along the left part of
      the atrioventricular groove and gave off a varying number of branches to the left
      ventricle and atrium along its course. It averaged 1.14 +/- 0.30 (SD) mm (range
      0.70-1.70 mm) in external diameter at its origin. The LAD averaged 1.28 +/- 0.25
      (SD) mm (range 0.90 +/- 1.80 mm) in external diameter at its origin. In 73% cases
      the LAD continued over the apex to course dorsally in the posterior
      interventricular groove, and gave off a varying number of diagonal and septal
      branches. The RCA arose from the right aortic sinus and coursed along the right
      part of the atrioventricular groove and averaged 0.94 +/- 0.15 (SD) mm (range
      0.70-1.20 mm) in external diameter at its origin. The posterior descending
      coronary artery (PDCA) arose from the LCA in 55% of the cases, and from the RCA
      in 45%. Myocardial bridges (MB) were present in 54% of the hearts and over the
      LCA branches exclusively. The average length of all MB was 5.68 +/- 3.31 (SD) mm
      (range 2.4-11.5 mm). The coronary arteries of Macaca fascicularis are medium
      sized muscular arteries with well developed tunics intima, media and adventitia,
      and so resemble human arteries more closely than the dog. Therefore, we suggest
      this primate species might be a useful model for physiological studies on the
      coronary circulation.

PMID- 9587904
TI  - Effect of dietary fat level on the calcium content of heart and kidney in DBA/2
      and C57BL/6 mice.
AB  - High-fat and low-fat diets were fed for 24 weeks to two strains of mice differing
      in susceptibility to the development of dystrophic cardiac calcinosis (DCC). The
      severity of DCC was assessed by histological examination and measurement of heart
      calcium concentrations. Plasma and renal tissue mineral levels were also
      measured. On the basis of macroscopic examination, feeding the high-fat diet did
      not influence the severity of DCC in the susceptible DBA/2 mice. Heart calcium
      concentrations were reduced in both strains; in DBA/2 mice more than in DCC
      resistant C57BL/6 mice. Cardiac concentrations of magnesium and phosphorus were
      similar in the two strains of mice and unaffected by the amount of dietary fat.
      Kidney calcium concentrations were higher in the DBA/2 than in the C57BL/6 mice
      and the high-fat diet also reduced kidney calcium concentrations in the DBA/2
      mice. The amount of dietary fat, at least during growth and maintenance, did not
      appear to affect the development of DCC in DBA/2 mice.

PMID- 9587906
TI  - Heterotopic pancreas at a site of colon stricture and ulceration in a guineapig.
AB  - A one-month-old female Dunkin Hartley guineapig presented with a thin hair coat
      and distended abdomen. Post-mortem findings after euthanasia were a protein-rich
      modified peritoneal transudate and heterotopic pancreas at a site of colon
      stricture and ulceration. Complications of pancreatic heterotopia are well
      recognized in man but not in animals. The finding in this individual is probably
      unrelated to sudden deaths in other animals in the group.

PMID- 9587905
TI  - Haematological and serum biochemical values in spontaneously epileptic male rats
      and related rat strains.
AB  - Haematological and serum biochemical measurements in male spontaneously epileptic
      rats (SER; double mutants homozygous for zitter and tremor genes) were compared
      with the values for related rat strains. Some haematological values were low in
      TRM rats and total leukocyte counts were high in ZI and TRM rats. TRM rats showed
      higher total cholesterol, phospholipid, high-density lipoprotein cholesterol and
      calcium values, and lower albumin value than Kyo: Wistar rats. Zitter homozygous
      rats including SER exhibited low total cholesterol, phospholipid and high-density
      lipoprotein cholesterol values. The SER showed an increase in urea nitrogen,
      aspartate aminotransferase and alanine aminotransferase values, and a decrease in
      glucose value, suggesting deterioration of the whole body with age.

PMID- 9587907
TI  - [Health effects of occupational diseases diagnosed in Poland during the years
      1990 and 1994].
AB  - The study was carried out on the material of 15,136 occupational diseases that
      accounted for 71.9% and 65.6% of all cases detected in 1990 and 1994,
      respectively. The analysis focused on the selected health effects of occupational
      diseases, such as sickness absenteeism, the transfer to other workposts, the
      percentage of health impairment and related single recompensation as well as
      disability pension. The study helped to draw many conclusions of great value, and
      disclosed major pathologies and their causes responsible for the range of related
      health effects. Long-term sickness absenteeism, high percentage of health
      impairment and related consequences for the country's economy (single
      recompensations and growing number of disability pensions paid due to
      occupational diseases), and low proportion of transfers to safe workposts were
      most striking among the effects in question. The study also contributed to
      initiating the establishment of the data base and the development of the system
      for data collection and analysis of information on health effects of occupational
      diseases in Poland.

PMID- 9587908
TI  - [Data processing computer system for evaluation of health effects due to
      occupational diseases diagnosed in Poland].
AB  - General consequences of occupational diseases for both employees and the
      country's economy have been known for many decades. Nevertheless there were no
      legal instruments and financial means to carry out studies leading to a
      comprehensive evaluation of health effects induced by occupational diseases
      diagnosed in Poland. Only recently, the legal basis has been provided by the
      revision of the regulations on occupational diseases (Official Journal of the
      Ministry of Health and Social Welfare no 9, heading 51, 1989), and the financial
      means allocated according to the Governmental Strategic Programme (SPR-1) for the
      years 1995-1998. The objectives of the study and the results obtained have been
      presented in another publication. Here the authors concentrated on some aspects
      of data collection and their analysis. An essential element in the establishment
      of data base on health effects of occupational diseases was its integration,
      namely the number of diagnosed occupational disease had to correspond with the
      entity in the Register of Occupational Diseases. Such an approach helped to avoid
      including in the base all metrical data, as information on effects of
      occupational diseases was collected exclusively for persons with detected and
      diagnosed occupational disease, which had to be previously placed in the Register
      of Occupational Diseases. The correctness of data input and the data analysis
      were carried out outside the Paradox system. The analysis of histograms of
      characteristics under study and the explanation of departing values were employed
      to evaluate the freedom from bias, and the statistical package for social
      sciences (SPSS) was used to analyse the data.

PMID- 9587909
TI  - [ANalysis of upper extremity injuries in the Szczecin shipyard S.A. in the years
      1989-1993].
AB  - The study covered 534 cases of work-related injuries of upper extremities among
      workers of the Szczecin Shipyard, registered during the years 1989-93. Some
      factors influencing the rate and structure of accidents (age, kind of work,
      section of the plant, occupational exposure and work experience) were analysed.
      The study showed that hand injuries were the most common effect of work-related
      accidents involving upper extremities among males employed in the shipyard.

PMID- 9587910
TI  - [Levels of immunoglobulin and subpopulations of T lymphocytes and NK cells in men
      occupationally exposed to microwave radiation in frequencies of 6-12 GHz].
AB  - Immunoglobulin concentrations and T-lymphocyte subsets in workers of TV re
      transmission and satellite communication centres were assessed. An increase in
      IgG and IgA concentrations, an increased count of lymphocytes and T8 lymphocytes,
      an decreased count of NK cells and a lower value of T-helper/T-suppressor ratio
      were found. Neither disorders in immunoglobulin concentrations nor in the count
      of T8 and NK cells had any clinical implications.

PMID- 9587912
TI  - [Safety health conditions for disposal of waste generated during the production
      of barium and boron compounds].
AB  - The authors proposed an approach to calculating maximum concentrations of dust in
      the ambient air that may occur during digging, loading and transportation of
      barium and boron wastes containing a variety of metallic compounds, including
      arsenic and nickel. In addition, they listed conditions which should be fulfilled
      in view of binding legal regulations, in order to ensure that the work performed
      does not create any health risk. It was recognized that maintaining dust
      concentrations in the air below 5 mg/m3 should protected workers against the
      potential risk during their work.

PMID- 9587911
TI  - [Coefficient of linear correlation between levels of fibrinogen, antithrombin
      III, thrombin-antithrombin complex and lipid fractions in women exposed
      chronically to carbon disulfide].
AB  - The authors examined 65 women, aged 22-58 years. They were derived from two
      industrial populations of different production profiles, and divided into three
      groups. Group I--the control group--was composed of 20 women, mean age 44.5 +/-
      12.02 years, employed in the DANA Enterprise, Szczecin, not exposed to carbon
      disulfide; Group II--the group studied--comprised 22 women, mean age 42.5 +/-
      4.95 years, employed in the WISKORD Enterprise, Szczecin, chronically exposed to
      carbon disulfide at the concentration of 9.36-23.4 mg/m2; and Group III--included
      23 women, mean age 46.7 +/- 8.81 years, suffering from diabetes mellitus II. The
      study reveals that carbon disulfide exerts significant adverse effect on plasma
      lipid fractions, and induces changes in the coagulation system, creating the risk
      of ischaemic diseases.

PMID- 9587913
TI  - [Criteria for classifying chemical substances according to toxicity: carcinogens,
      irritants, corrosives, allergens, fetotoxins and those absorbed through the
      skin].
AB  - The authors reviewed and presented the criteria used to classify the toxic
      effects of chemicals such as carcinogenic, irritation, corrosive, allergic, and
      fetotoxicity, as well as dermal absorption of chemical agents. The criteria for
      assigning symbols to the Polish list of chemical MAC values has not as yet been
      determined. Following the analysis it may be concluded that all chemical
      compounds, which satisfy the requirements should be indexed on the MAC list.

PMID- 9587914
TI  - [Compartment simulation models and physiologic use in pharmaco- and
      toxicokinetics].
AB  - The pharmaco- and toxicokinetic studies describe the process of absorption,
      distribution, metabolism and elimination of drugs or chemical compounds in
      animals and humans. In simple compartmental models, the body is divided into
      basic compartments, central and peripheral. The central compartment is an
      equilibrium of arterial and venous blood flows, and the peripheral one is
      connected to the central compartment through a series of flow rate constants that
      describe the flow of chemicals in both directions. For instance, we can use the
      PH/EDSIM software for calculating the constants. The flow of the material from
      one to the other reflected by vectorial connections of two types of kinetics:
      linear and Michaelis-Menten (nonlinear). At present, the PB-PK models
      (physiologically-based pharmacokinetic models), which rely on actual
      physiological (breath rates, blood flow rates and tissue volumes), biochemical
      and metabolic parameters, tend to be more commonly used. Tissue groups or
      compartments that are frequently applied in PB-TK model include organs, muscle,
      fat tissue and the liver. Tissue compartments are connected by arterial and
      venous blood flows, and each compartment is characterised by a unique set of
      differential equations. The flow rate constants that describe that flow of
      materials from and to the compartments, and the rate of change in the amount of
      chemical in each compartments are directly proportional to the blood flow rate,
      tissue solubility and organ value.

PMID- 9587915
TI  - [Biological effects of non-ionizing electromagnetic radiation].
AB  - Since the mid 1970's, when Adey discovered that extremely-low-frequency
      electromagnetic field (ELF EMF) may affect the calcium ions efflux from various
      cells, bioeffects of non-ionizing radiation (NIR) have become the subject of
      growing interest and numerous research projects. At present, the fact that NIR
      exerts both stimulatory and inhibitory effects on different physiological
      cellular parameters is rather unquestionable. At the same time, some
      epidemiological studies suggest that exposure to EMF is potentially harmful even
      if its intensity is very low. It has been proved that thermal factors are not
      responsible for these effects, therefore nowadays, they are called 'non-thermal
      effects'. Our paper deals with three different aspects of biological effects of
      non-ionizing radiation, bioelectromagnetism, electromagnetobiology and
      electromagnetic bioinformation. Firstly, we describe how EMF and photons can be
      produced within a living cell, how biological cycles are controlled, and what are
      the features of endogenous electromagnetic radiation. Secondly, we discuss
      various facets of external EMF interactions with living matter, focusing on
      extremely-low-frequencies, radio- and microwaves. Possible mechanisms of these
      interactions are also mentioned. Finally, we present a short overview of current
      theories which explain how electromagnetic couplings may control an open and
      dissipative structure, namely the living organism. The theory of electromagnetic
      bioinformation seems to explain how different physiological processes are
      triggered and controlled, as well as how long-range interactions may possibly
      occur within the complex biological system. The review points out that the
      presented research data must be assessed very carefully since its evaluation is
      crucial to set the proper limits of EMF exposure, both occupational and
      environmental. The study of biological effects of non-ioinizing radiation may
      also contribute to the development of new diagnostic and therapeutic methods.

PMID- 9587916
TI  - Corticosterone exacerbates cyanide-induced cell death in hippocampal cultures:
      role of astrocytes.
AB  - Previous study demonstrated that, in hippocampal neuron/glia mixed cultures,
      glucocorticoids (GCs) enhanced extracellular overflow of [3H]D-aspartate [3H]D
      Asp) by decreasing its uptake, thereby aggravating cell death during cyanide
      induced ischemia. Since neuronal and glial cells respond to ischemic insult and
      GC differently, this study further evaluated the relative significance of these
      cells in GC endangering ischemic cell death. Using D-[2,3-3H]aspartic acid ([3H]D
      Asp) as a tracer, it was found that corticosterone (CORT, the physiological GC in
      rat) enhanced the overflow of extracellular [3H]D-Asp in astrocyte cultures and,
      to a lesser extent, in neuron-enriched cultures during cyanide-induced ischemia.
      Analysis of [3H]D-Asp uptake kinetics indicates that CORT reduced the maximum
      uptake rate in cultured astrocyte, but not in neurons, after cyanide exposure. It
      is concluded that, during cyanide-induced ischemia, CORT might mainly the ability
      of astrocytes to clear excitatory amino acids from the synapse, thus exacerbating
      the damaging cascade of these amino acids.

PMID- 9587917
TI  - The vesicular monoamine transporter: from chromaffin granule to brain.
AB  - All characterized monoaminergic cells utilize the same transport system for the
      vesicular accumulation of monoamines prior to their release. This system operates
      in neuronal (catecholaminergic, serotoninergic or histaminergic) as well as in
      endocrine or neuroendocrine cells. For several decades, chromaffin granules from
      bovine adrenal medulla have been used as a model system, allowing progress in the
      understanding of the biophysics, the biochemistry and the pharmacology of the
      monoamine vesicular transporter. The transporters from rat, bovine and man have
      been cloned. Surprisingly, two genes encode different isoforms of the protein
      which are differentially expressed in monoaminergic systems. The conjunction of
      recombinant DNA techniques and expression in secretory or non-secretory cells
      with the large body of data obtained on the chromaffin granule transporter has
      allowed rapid progress in the study of the protein. But interestingly enough,
      this progress has open new possibilities in the study of biological problems,
      especially in the brain. The transporter is useful for the determination of the
      relationship between small and large dense core vesicles, for the understanding
      of the mechanism of the drugs such as 1-methyl-4-phenylpyridinium (MPP+),
      tetrabenazine or amphetamines, and as a marker in brain development. The
      possibility of regulations at the vesicular transporter level and of their effect
      on the quantum size has to be investigated. The vesicular monoamine transporter
      is also an important target for brain imaging.

PMID- 9587918
TI  - Analysis of purine and pyrimidine bases, nucleosides and deoxynucleosides in
      brain microsamples (microdialysates and micropunches) and cerebrospinal fluid.
AB  - A new chromatographic method is reported for the synchronous analysis of
      endogenous purine and pyrimidine bases, ribonucleosides, and deoxyribonucleosides
      in brain samples. An optimized gradient chromatography system with a cooled
      reversed-phase column allows the detection of these compounds in very low
      concentrations in microsamples (microdialysates and micropunches).
      Chromatographic peaks were identified via the retention times of known standards,
      with detection at two wavelengths, and also by electrospray tandem mass
      spectrometry, which permits the identification of certain compounds at extremely
      low concentrations. The method was tested on in vivo brain microdialysis samples,
      micropunch tissue sample and cerebrospinal fluid of rats. Extracellular
      concentrations of pyrimidine metabolites in brain samples and of various purine
      metabolites in thalamic samples are reported here first. A comparison of the
      results on microdialysis and cerebrospinal fluid samples suggests that the
      analysis of cerebrospinal fluid provides limited information on the local
      extracellular concentrations of these compounds. Basic dialysis experiments
      revealed temporarily stable baseline levels one hour after implantation of the
      microdialysis probes. An elevated potassium concentration in the perfusion
      solution caused increases in the extracellular levels of adenosine and its
      metabolites, and of guanosine and the pyrimidine nucleoside uridine.

PMID- 9587919
TI  - Effect of various depolarizing agents on endogenous amino acid neurotransmitter
      release in rat cortical neurons in culture.
AB  - The purpose of this study is to determine whether differences in membrane
      potential and/or intracellular Ca2+ increments are implicated in a programmed
      release of amino acid neurotransmitters (aspartate, glutamate, glycine and GABA)
      in cortical neurons in culture. According to our results, it is possible to
      assume that difference in membrane potential is not the only signal which starts
      the amino acid neurotransmitter release, but there are other necessary conditions
      at the start of this amino acid release. One of these conditions could be the
      increment in intracellular Ca2+, but our results indicate that, in cortical
      neurons in culture, the total intracellular Ca2+ increments are not important on
      release levels, but are the stimulating agent which produces this intracellular
      Ca2+ increment. From these results we may infer: (1) that in rat cortical neurons
      there are neurons which contain and release glutamate, aspartate, glycine and
      GABA, (2) that in cortical neurons the 36.6 +/- 5.8% of the neurons are GABA
      ergic, (3) that the membrane potential and the total intracellular calcium are
      not only responsible for the release of these amino acids but also the
      depolarizing agent which plays an important role in this release, and (4) that
      glutamate and aspartate and glutamate and GABA are localized in different
      vesicular pools or in different cell neurons.

PMID- 9587920
TI  - Characterization of cyclothiazide-enhanced kainate excitotoxicity in rat
      hippocampal cultures.
AB  - Cyclothiazide has been shown to block desensitization of alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid (AMPA)-preferring receptors and to enhance
      quisqualate-, AMPA- and kainate-induced neurotoxicity. The pharmacology behind
      this cyclothiazide-enhanced kainate-induced excitotoxicity was characterized in
      embryonic rat hippocampal cell cultures. Treatment of cell cultures with a
      combination of cyclothiazide and kainate for 24 h resulted in excessive neuronal
      death as measured by the release of lactate dehydrogenase into the culture media.
      Cyclothiazide produced a leftward shift of the kainate dose-response curve and
      enhanced the maximum response of kainate excitotoxicity. AMPA-preferring receptor
      antagonists, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline(NBQX) and 1
      (4-amino-phenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466)
      blocked cyclothiazide-enhanced kainate toxicity completely, and cyclothiazide
      increased the IC50S for NBQX and GYKI 52466 against kainate toxicity. The N
      methyl-D-aspartate (NMDA) antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]
      cyclohepten-5,10-imine (MK801) also blocked cyclothiazide-enhanced kainate
      toxicity, but only partially. Cyclothiazide also increased the IC50 for MK801
      against kainate toxicity. These data suggest that cyclothiazide enhances both
      AMPA-preferring receptor- and NMDA receptor-mediated toxicity in kainate-induced
      toxicity in embryonic rat hippocampal cultures.

PMID- 9587921
TI  - Evaluation of MAO activities on murine neuroblastoma cells upon acute or chronic
      treatment with aluminium (III) or tacrine.
AB  - Monoamine-oxidase catalyses the oxidative deamination of various primary amines
      such as norepinephrine, serotonin, dopamine and others. Such an enzyme exists
      under two well known isotypes, A and B. In the brain monoamine-oxidase activity
      increases with ageing. The present paper reports data regarding the evaluation on
      the activity of monoamine-oxidase A and B in murine neuroblastoma cells carried
      out by a radioassay upon acute or chronic treatment of cells by aluminium or
      tacrine. Our data show that aluminium has a pronounced activatory effect on both
      enzymatic isoforms either in acute or long-term adaptation treatment. Conversely,
      tacrine produces an inhibitory effect of both monoamine oxidase isotypes after an
      acute treatment, while an inhibitory effect on the isoform A and an activation of
      the isoform B in long-term adaptation was observed. Such effects are discussed in
      terms of aluminium neurotoxicity and therapeutic implications for tacrine.

PMID- 9587922
TI  - Excitatory amino acid receptor antagonists decrease hypoxia induced increase in
      extracellular dopamine in striatum of newborn piglets.
AB  - The present study tested the hypothesis that the increase in extracellular
      striatal dopamine during hypoxia is least partly associated with activation of N
      methyl-D-aspartate (NMDA) and/or non-NMDA excitatory amino acid receptors.
      Studies were performed in anesthetized and mechanically ventilated 2-3 days old
      piglets. Hypoxic insult was induced by decreasing the oxygen fraction in inspired
      gas (FiO2) from 22 to 7% for 1 h, followed by 1 h reoxygenation at 22%. Cortical
      oxygen pressure was measured optically by oxygen dependent quenching of
      phosphorescence, and extracellular striatal dopamine was measured using in vivo
      microdialysis. The microdialysis probes were perfused with Ringer solution +/- 50
      microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate
      (MK-801) or 50 microM 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline
      (NBQX). One hour of hypoxia decreased the cortical oxygen pressure from 46 +/- 3
      Torr to 10 +/- 1.8 Torr. In striatum perfused with Ringer, statistically
      significant increase in extracellular dopamine, to 1050 +/- 310% of control, was
      observed after 20 min of hypoxia. By 40 min of hypoxia the extracellular level of
      dopamine increased to 4730 +/- 900% of control; by the end of the hypoxic period
      the values increased to 18,451 +/- 1670% of control. The presence of MK-801 in
      the perfusate significantly decreased the levels of extracellular dopamine during
      hypoxia. At 20, 40 and 60 min of hypoxia extracellular level of dopamine
      increased to 278 +/- 94% of control, 1530 +/- 339% of control and 14,709 +/- 1095
      of control, respectively. The presence of NBQX caused a statistically significant
      decrease, by about 30%, in the extracellular dopamine compared to control, only
      at the end of the hypoxic period. It can be concluded that in striatum of newborn
      piglets, the excitatory NMDA receptors but not the non-NMDA receptors may be
      modulating the changes in extracellular levels of dopamine. The NMDA receptor
      antagonist, MK-801, may exert part of its reported neuroprotective effect to
      hypoxic stress in striatum by decreasing the levels of extracellular dopamine.

PMID- 9587923
TI  - Neurosteroid modulation of GABA binding sites in developing avian central nervous
      system.
AB  - Our aim was to examine the effect of the potent neurosteroid 3 alpha-hydroxy-5
      alpha-pregnan-20-one (3 alpha, 5 alpha-P) on [3H]-GABA binding to its receptor
      sites in the chick optic lobe. Binding was performed on synaptic membranes
      isolated at different stages of development and two different membrane
      preparation procedures were applied to expose high and low affinity GABA binding
      sites. The addition of 3 alpha, 5 alpha-P was shown to increase [3H]-GABA binding
      in an age- and concentration-dependent manner. Maximal stimulation for low
      affinity GABA binding sites was observed at hatching (130% enhancement), in fresh
      washed as well as in frozen membranes. Saturation analysis performed on both
      membrane types disclosed that 3 alpha, 5 alpha-P increases the affinity of low
      affinity GABA binding sites without altering their maximal binding capacity. On
      the other hand, the augmenting effect at high affinity sites, displayed only in
      frozen membranes, was roughly 50% for all developmental stages. However, their
      saturation binding parameters remained unaltered in the presence of the steroid,
      suggesting that stimulation of such sites seems due to interference exerted by
      the low affinity site population. Findings indicate that 3 alpha, 5 alpha-P acts
      as an allosteric modulator only for low affinity GABA binding sites, displaying
      an age-dependent profile probably related to plastic events during visual pathway
      development.

PMID- 9587925
TI  - Summary of ocular genetic disorders and inherited systemic conditions with eye
      findings.
AB  - Of the close to 10,000 known inherited disorders that affect humankind, a
      disproportionately high number affect the eye. The total number of genes
      responsible for the normal structure, function, and differentiation of the eye is
      unknown, but the list of these genes is rapidly and constantly growing. The
      objective of this paper is to provide a current list of mapped and/or cloned
      human eye genes that are responsible for inherited diseases of the eye. The
      ophthalmologist should be aware of recent advances in molecular technology which
      have resulted in significant progress towards the identification of these genes.
      The implications of this new knowledge will be discussed herein.

PMID- 9587924
TI  - Tamoxifen alters dopamine output through direct actions upon superfused corpus
      striatal tissue fragments.
AB  - Tamoxifen (10 pg/ml) was infused directly into superfused striatal tissue
      fragments of ovariectomized rats for a 50 min period. Immediately following the
      termination of tamoxifen there was a significant increase in dopamine output
      compared with non-infused controls. No such significant increase was observed
      with use of a 100 pg/ml tamoxifen dose. Although dopamine output was again
      increased upon termination of a 2 h infusion of tamoxifen, these levels failed to
      differ significantly from that of non-infused controls. Similarly, a shorter 10
      min duration infusion of tamoxifen failed to alter dopamine output. Finally, we
      examined whether the tamoxifen-induced, post-infusion increase in dopamine
      output, as observed following a 50 min infusion of 10 pg/ml, involved a calcium
      dependent process. To achieve this goal, superfusions were performed with
      Calcium/Tamoxifen, No Calcium/Tamoxifen, No Calcium/No Tamoxifen and Calcium/No
      Tamoxifen. A significant increase in dopamine output post-tamoxifen infusion was
      obtained for the Calcium/Tamoxifen condition compared with the remaining three
      groups which failed to differ from one another. Taken together these results show
      that tamoxifen can alter dopamine output through direct, non-genomic effects upon
      striatal neurons. Responses to this anti-estrogen are intriguing since they are
      apparent following removal, but not during tamoxifen infusion and represent a
      calcium-dependent process. These data suggest that tamoxifen may represent an
      important modulator of nigrostriatal dopaminergic function.

PMID- 9587926
TI  - A practice-based survey of familial age-related maculopathy.
AB  - PURPOSE: We evaluated the efficacy of a practice-based survey of age-related
      maculopathy (ARM) to identify potential families for molecular genetic studies.
      Demographic and ophthalmic features of the eligible study population were
      compared with responders and with individuals who reported a positive family
      history of ARM. METHODS: Individuals seen within a three-year period in a
      comprehensive ophthalmic practice were identified through billing codes. Clinical
      records were reviewed, coded, and merged with questionnaire responses. Patient
      identifiers were removed prior to analyses. RESULTS: There were no significant
      differences between the respondents and the eligible cohort with respect to
      gender, age, or type of macular degeneration. Comparable percentages of younger
      and older individuals with ARM reported positive family histories. The
      distribution of atrophic macular degeneration, choroidal neovascular membranes,
      and milder forms of the disease among the individuals reporting positive family
      histories corresponded to the distribution of the entire eligible cohort of
      patients. CONCLUSIONS: This recruitment strategy for ARM families is cost
      effective and confirmed a high prevalence of familial ARM. The respondents are
      representative of the general ARM population. This approach is applicable for
      other ophthalmic genetic conditions.

PMID- 9587927
TI  - Phenotypic expression of autosomal dominant retinitis pigmentosa in a Swedish
      family expressing a Phe-211-Leu variant of peripherin/RDS.
AB  - PURPOSE: To characterize the clinical phenotype, with emphasis on
      electrophysiology, of members of a Swedish family with autosomal dominant
      retinitis pigmentosa due to a novel mutation, F211L, in the peripherin/RDS gene.
      METHODS: Nine patients with autosomal dominant retinitis pigmentosa and two
      healthy family members underwent a full clinical evaluation including kinetic
      visual field testing, measurement of dark adaptation threshold, and full-field
      electroretinography. Blood samples were collected and DNA analysis was performed
      using denaturing gradient gel electrophoresis (DGGE). RESULTS: The grandfather,
      six of seven siblings from the middle generation, and two young boys carried the
      mutation F211L in the peripherin/RDS gene. The mutation segregated with the
      clinical presentation of disease. Fundus examination revealed mainly macular
      atrophy. All assessed parameters of retinal function (visual acuity, dark
      adaptation threshold, visual fields, and full-field electroretinograms)
      demonstrated a successive reduction with increasing age. Full-field
      electroretinograms showed a diminished rod response in all affected individuals
      and a reduction of the cone b-wave amplitudes with increasing age, indicating
      retinitis pigmentosa. In the affected family members, the disease seems to
      progress at a similar rate with increasing age. CONCLUSIONS: The peripherin/RDS
      gene mutation F211L is associated with a clinical phenotype and includes early
      loss of rod function and successive reduction of cone function with increasing
      age, but impressively well-preserved visual acuity and visual fields in young and
      middle-aged patients and moderately reduced vision in the old patient. Compared
      to previously described phenotypes segregating with mutations in the
      peripherin/RDS gene, the present family demonstrates a more benign clinical
      phenotype, which is concordant within the family.

PMID- 9587929
TI  - Prolidase deficiency associated with pathologic myopia.
AB  - Deficiency of prolidase, a key enzyme in proline metabolism, is extremely rare
      and is usually associated with skin lesions, recurrent infections, characteristic
      facies, mental retardation, and splenomegaly. These clinical features are largely
      due to inhibition of normal recycling of proline, which causes an alteration in
      the metabolism of collagen and other proline-rich proteins. The case of a 25-year
      old with all the recognized characteristics of prolidase deficiency is reported.
      Pathologic myopia, which has not been hitherto described in association with
      prolidase deficiency, is added to the clinical spectrum of this rare disorder.

PMID- 9587928
TI  - Microcephaly with chorioretinal degeneration.
AB  - PURPOSE: To describe the ophthalmologic findings and electroretinograms in
      patients with microcephaly and chorioretinal degeneration. METHODS: We reviewed
      the hospital records of 20 patients with microcephaly that was not part of a
      recognizable syndrome prior to initial referral to the institutional consultative
      practice of one of the authors (RGW). Twelve patients, all from separate
      families, were diagnosed as having microcephaly with chorioretinopathy. Ten of
      these patients had ISCEV-standard electroretinograms (ERG). RESULTS: No family
      history of microcephaly or retinal degeneration was found in any of our patients.
      Three patients had another family member with mental retardation. Three of the 12
      were compatible with the autosomal dominant form of microcephaly with
      chorioretinopathy (MIM 156590), possibly as a new mutation. Eight patients, who
      had fundus findings of retinitis pigmentosa, were similar to the autosomal
      recessive form of microcephaly with chorioretinal degeneration (MIM 251270). The
      ERGs were moderately to severely subnormal for responses of both rods and cones.
      The retinal findings varied from no pigmentary changes, pigment clumping and bone
      spicules, pigmentary granularity, bull's eye maculopathy, choroidal and retinal
      atrophy, to lacunar depigmentation. Mental retardation was mild to profound. The
      abnormal findings from MRI/ CT brain scans (8 patients) were cerebellar atrophy
      (2), agenesis of cerebellar vermis (1), cortical atrophy (1), and pachygyria (1).
      Dysmorphic features were present in most patients. Chromosome studies were
      normal, except for one patient with ring chromosome 14. CONCLUSIONS: Although the
      patients reviewed in this study represent a heterogeneous group of disorders,
      ocular abnormalities, especially retinal degeneration, are frequent among
      patients with microcephaly.

PMID- 9587930
TI  - Stickler's syndrome associated with congenital glaucoma.
AB  - A case report of Stickler's syndrome associated with congenital glaucoma is
      presented. Stickler's syndrome is an autosomal dominant disorder characterised by
      progressive arthropathy, midfacial flattening, Pierre Robin anomaly or cleft
      palate, sensorineural hearing loss, progressive myopia, vitreoretinal
      degeneration, and retinal detachment. Congenital glaucoma and Stickler's syndrome
      are two diagnoses frequently considered in high myopia in infancy. The case
      report described presents a case of Stickler's syndrome in association with
      congenital glaucoma. This association is unusual, but important to recognise in
      the neonatal period. The possibility of coexistence of these clinical entities,
      should be considered in the future.

PMID- 9587931
TI  - Correlation of TGF-alpha and EGF-receptor expression with proliferative activity
      in human astrocytic gliomas.
AB  - Fifty-nine paraffin-embedded astrocytic gliomas (four WHO grade 1, 21 WHO grade
      2, 17 WHO grade 3 and 17 glioblastomas, WHO grade 4) were immunohistochemically
      investigated for expression of transforming growth factor-alpha (TGF-alpha),
      epidermal growth factor receptor (EGF-R) and oncoprotein c-erbB-2 by
      semiquantitative assessment. Proliferative activity was simultaneously analyzed
      by using the antibody Ki-67 (MIB-1). Immunostaining in neoplastic cells was
      quantified by image analysis. Concerning the antibodies used, the percentage of
      immunoreactive cells increased with histologic malignancy. There was no
      expression of EGF-R and c-erbB-2 in the majority of low-grade astrocytomas.
      However, small focal expressions of TGF-alpha and EGF-R were observed in several
      low-grade astrocytomas (11/25), suggesting an early stimulation of malignant
      transformation. With regard to percentage, a strong positive correlation between
      TGF-alpha and EGF-R-stained cells was found, indicating an autocrine stimulation
      of the mitogenic pathway of the TGF-alpha/EGF-R system. Likewise, indices of EGF
      R and c-erbB-2 positive cells correlated significantly. Less significant
      correlations were also seen between EGF-R, c-erbB-2 frequencies and the Ki-67
      labeling index. However, there was no correlation between TGF-alpha and Ki-67
      indices. The results suggest that TGF-alpha expression is not directly related to
      the proliferative potential as judged by the Ki-67 labeling index. Furthermore,
      besides EGF-R and c-erbB-2, other growth factors and their receptors or mutant
      EGF-R might participate in the proliferative activity of gliomas.

PMID- 9587932
TI  - Multidrug resistance in glioblastoma. Chemosensitivity testing and
      immunohistochemical demonstration of P-glycoprotein.
AB  - Chemosensitivity of previously untreated glioblastomas to mitoxantrone,
      methotrexate, ACNU and BCNU was tested on cultured tissue. Sixteen of 62 tumors
      were partially chemosensitive in vitro. The monoclonal antibody C 219 was used to
      demonstrate the presence of p-glycoprotein in the 16 sensitive and five highly
      resistant glioblastomas. All 21 tumors identically expressed p-glycoprotein.
      These results show that untreated glioblastomas primarily express p-glycoprotein
      even if they are at least partially chemosensitive in vitro. Therefore,
      immunohistochemical demonstration of p-glycoprotein with the monoclonal antibody
      C 219 can not provide reliable information on short term resistance of the
      individual tumors to antineoplastic drugs. P-glycoprotein expression could,
      however, help to explain the disappointing overall long-term efficacy of
      chemotherapy by showing the existence of cell populations with early drug
      resistance in these tumors.

PMID- 9587933
TI  - p53 and ras mutations in Ewing's sarcoma.
AB  - The role of tumor suppressor genes and oncogenes in the development of Ewing's
      sarcoma has not yet been fully clarified. In this study, we analyzed the
      frequency of p53 tumor suppressor gene mutation in exons 4-8 by PCR-SSCP and
      direct sequencing, and the expression of p53-protein in Ewing's sarcoma (ES) by
      using immunohistochemistry. The overexpression of MDM2, which acts as a
      functional inactivator of p53, was studied by immunohistochemistry. In addition,
      a screening for point mutations in the hot spot regions codon 12 and 13 of exon 1
      and codon 61 of exon 2 of ras-genes (H-ras, N-ras, K-ras) was performed. In one
      case, a p53 gene mutation could be confirmed in codon 238 of exon 7 (1/24).
      Overexpression of MDM2 was found in five cases; in ras-genes, no mutations were
      detected. Compared with other highly malignant mesenchymal pediatric tumors such
      as osteosarcomas, mutations of p53 and ras in Ewing's sarcomas are an
      extraordinarily rare event. However, their frequency is comparable to that of
      PNET, suggesting that the low incidence of these mutations in ES and PNET could
      be group-specific for tumors of neuroectodermal genesis.

PMID- 9587934
TI  - Detection of the apoptosis-suppressing oncoprotein bcl-2 in salivary gland
      lymphoma.
AB  - The bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that
      blocks apoptosis and programmed cell death in human lymphoid tissue. In this
      study a monospecific anti-human bcl-2 antibody that is reactive in formalin-fixed
      tissues was used with an avidin-biotin complex immunoperoxidase method to
      evaluate 41 cases of lymphoproliferative disorders of the salivary gland. The
      study cases were 26 primary salivary gland lymphomas (including 21 B-cell
      lymphomas four T-cell lymphomas and one true histiocytic lymphoma) and 15 cases
      of myoepithelial sialadenitis. Bcl-2 expression is restricted to the mantle zone
      and interfollicular lymphocytes around reactive germinal centers of myoepithelial
      sialadenitis. Seventeen of the 21 B-cell lymphomas were positive for bcl-2, and
      were composed of mucosa-associated lymphoid tissue (MALT), centrocytic,
      centroblastic-centrocytic and centroblastic lymphomas. Noticeably, all 11 cases
      of MALT lymphoma were bcl-2 positive. In contrast, staining for bcl-2 was present
      in only one of four cases of T-cell lymphomas and was negative in one true
      histiocytic lymphoma. The expression of bcl-2 protein was also investigated in
      the ductal systems and epimyoepithelial islands of salivary glands from patients
      with malignant lymphoma and myoepithelial sialadenitis. While salivary ducts in
      eight of 15 cases of myoepithelial sialadenitis immunostained for bcl-2,
      epimyoepithelial islands showed bcl-2 expression in only five cases of
      myoepithelial sialadenitis. We found that ductal cells in the salivary gland from
      patients with primary non-Hodgkin's lymphomas expressed bcl-2 protein. It was of
      interest that epimyoepithelial islands in all cases of MALT lymphoma displayed
      bcl-2 expression whereas other subtypes of B-cell lymphoma, T-cell lymphoma and
      true histiocytic lymphoma were invariably negative. These results indicate that
      bcl-2 is expressed in a wide variety of non-Hodgkin's lymphomas, especially when
      all 11 cases of MALT lymphoma are bcl-2 positive. Epimyoepithelial islands in
      MALT lymphoma express this oncoprotein, and their ability to induce bcl-2
      synthesis resulted in the prevention of apoptosis and prolonged cell survival.
      Furthermore, the expression of bcl-2 protein in the lymphoma cells may be
      responsible for the induction of bcl-2 expression in the adjacent
      epimyoepithelial islands through a lymphocyte chemical mediator.

PMID- 9587936
TI  - A simple method of tumour culture.
AB  - We describe a simple explant primary cell culture system which maintains the
      normal tumour stroma relationship. This technique utilises conventional cell
      culture methods combined with the skills found in the histopathological
      laboratory. This produces sections of tumour visible by light microscopy. Using
      this method we were able to maintain for up to 7 days good morphological
      preservation and demonstrated continued proliferation. This technique produces
      histological sections of tumour following in vitro culture that can be utilised
      for other molecular studies, e.g. immunohistochemistry and in situ PCR. This
      method should prove invaluable to pathologists enabling direct visualisation and
      localisation of molecular events involved in tumour growth.

PMID- 9587935
TI  - The pS2 protein in colorectal carcinomas and metastases.
AB  - Expression of pS2 protein in 50 primary tumors, metastases and recurrent tumors
      of colorectal carcinomas has been analyzed by immunohistochemistry. Sixty percent
      of the primary tumors were at least focally positive for the antigen. There was
      no correlation between pS2 expression and histologic grade of the lesions. In
      contrast, pS2 expression in T4 and T3 tumors was significantly higher than in T2
      carcinomas. Immunoreactions in carcinomas with distant metastases (MI) were
      stronger than in M0 cases. However, this difference did not reach statistical
      significance. The presence of lymph node metastases did not correlate with pS2
      expression. High expression of pS2 in T4 and T3 carcinomas together with the
      finding of pronounced expression of the antigen at invasion fronts in single
      cases could be interpreted as a function in tumor cell invasion and motility.
      However, in metastases and recurrent tumors, pS2 expression did not differ from
      primary lesions (53% positive lesions). All in all, under consideration of the
      latter finding in particular and together with the randomly distributed
      immunopositive tumor cells and cell clusters in the majority of cases, it is more
      likely that the expression pattern of pS2 in colorectal carcinomas is a result of
      overall tumor cell heterogeneity.

PMID- 9587937
TI  - Primary angiosarcoma of the ovary: a clinicopathologic, immunohistochemical and
      electronmicroscopic study.
AB  - The present report of a 25 year old woman with a primary ovarian angiosarcoma is
      supplemented by histochemical and ultrastructural studies and reviews the
      literature of this extremely rare neoplasm. Since this ovarian tumor, especially
      in young women, may constitute a diagnostic pitfall, problems relating to
      differential diagnosis are emphasized. Although the origin of this neoplasm
      appears to occur most likely from the rich ovarian vasculature, other less
      conventional histogenetic theories such as a possible origin in mixed mullerian
      tumor, in teratoma or in other ovarian germ cell tumors have also been proposed
      and are considered in this paper.

PMID- 9587938
TI  - Subtotal liver calcification due to epithelioid hemangioendothelioma.
AB  - A hepatic epithelioid hemangioendothelioma leading to almost complete
      calcification of the right and left liver lobes in a 75-year-old female is
      reported. Over a period of 16 years the liver progressively calcified, but its
      function remained normal by compensatory hypertrophy of the caudate lobe.
      Multiple partially calcified metastases were present in the lungs, peripancreatic
      region and along the left principal bronchus. Extreme liver calcification has
      only rarely been reported. The case presented here reflected slow tumor growth
      and subsequent long disease course. The vascular nature of the tumor was
      confirmed by immunohistochemical and ultrastructural analysis.

PMID- 9587939
TI  - Signet-ring cell aggregates simulating carcinoma in colon and gallbladder mucosa.
AB  - We describe three cases of benign signet-ring cell aggregates in the colon
      associated with pseudomembranous colitis, adenomatous polyp of the colon and
      ulcerated mucosa of the gallbladder excised for gallstones. In all cases, we
      found loose, benign signet-ring cell aggregates overlying the ulcerated mucosa
      surface, simulating signet ring-cell carcinoma. The most important sign of the
      benign signet-ring cell aggregates is that they are always confined to the
      surface of the mucosa of the intestine or gallbladder mucosa or crypts of the
      intestinal epithelium. In no case did we see an invasion of these cells into the
      lamina propria of the mucosa. In all cases, the benign signet-ring cell
      aggregates were immunohistochemically positive with antibodies to cytokeratins.
      The occurrence of benign signet-ring cell aggregates is a rare and very
      misleading diagnostic pitfall which must be differentiated from signet-ring cell
      carcinoma of the colon and gallbladder.

PMID- 9587941
TI  - Intracranial plasma cell granuloma and homocystinuria.
AB  - A rare case of plasma cell granuloma (PCG) of the brain is reported. An 18-year
      old man with a well known homocystinuria and a history of severe oligophrenia,
      grand-mal-epilepsia, bilateral ectopia lentis requiring extraction of both lens
      and operatively correlated genu valgum, died suddenly within a few minutes. In
      1993 a hypergammaglobulinemia was noticed and a decortication on the left side
      after purulent pneumonia became necessary. Four months before death, multiple
      abscesses in the spleen and pancreas led to splenectomy and resection of the
      pancreatic tail. Autopsy revealed a pulmonary embolism and an isolated
      intracranial plasma cell granuloma of the left hemisphere.

PMID- 9587940
TI  - Primary pigmented nodular adrenocortical dysplasia.
AB  - A 29-year-old female patient presented clinical features of Cushing's syndrome.
      Biochemical tests suggested the presence of an autonomously functioning
      adrenocortical neoplasm. However, the adrenal glands were normal on MRI.
      Diagnostic adrenalectomy revealed a slightly enlarged organ studded externally
      and on multiple cut surfaces by small yellow and brown nodules. Microscopically,
      the nodules were composed of enlarged cortical cells with eosinophilic cytoplasm
      and nuclear pleomorphism, without mitotic figures. The morphology was consistent
      with primary pigmented nodular adrenocortical dysplasia (PPNAD). Additional right
      adrenalectomy was performed for curative treatment of Cushing's syndrome. The
      pathogenesis of PPNAD is not yet established, though, a defect on chromosome 16
      was recently suggested. Since our patient had a malignant melanoma earlier in her
      history, the PPNAD may be a manifestation of the Carney complex.

PMID- 9587942
TI  - Intra-abdominal pulmonary sequestration associated with congenital cystic
      adenomatoid malformation of the lung: just an unusual combination of rare
      pathologies?
AB  - A case of intra-abdominal pulmonary sequestration associated with histological
      features of congenital cystic adenomatoid malformation (CCAM) of the lung is
      reported. The lesion consisted of a Stocker type II CCAM in which numerous
      striated muscle cells were present. A review of the literature of this rare
      combination of congenital pulmonary anomalies is presented.

PMID- 9587944
TI  - Opportunities in drug discovery for treatment of AIDS.

PMID- 9587943
TI  - Microcrystalline cellulose as a sponge as an alternative concept to the
      crystallite-gel model for extrusion and spheronization.

PMID- 9587945
TI  - Genetic polymorphism of drug metabolizing enzymes: new mutations in CYP2D6 and
      CYP2A6 genes in Japanese.
AB  - Genetic polymorphism of drug metabolizing enzymes, particularly cytochrome
      P450(CYP), is an important cause of adverse drug reactions. Multiple gene
      mutations in CYP have been shown to be phenotype. The occurrence of genetic
      polymorphism has been seen in genes for CYP1A1, CYP2A6, CYP2C9, CYP2C19, CYP2D6,
      CYP2E1 and CYP3A5. This review discusses the molecular mechanism of two genetic
      polymorphisms, debrisoquine/sparteine (CYP2D6) coumarin (CYP2A6) polymorphisms.
      In addition, elucidation of gene mutations of CYP2D6 and CYP2A6 in Japanese will
      be discussed.

PMID- 9587946
TI  - Influence of liposome bilayer fluidity on the transport of encapsulated substance
      into the skin as evaluated by EPR.
AB  - PURPOSE: The influence of liposome composition on the bilayer fluidity and on the
      transport of encapsulated substance into the skin was investigated. METHODS:
      Multilamellar vesicles (MLV) from dipalmitoylphosphatidylcholine (DPPC) or
      dimyristoylphosphatidylcholine (DMPC) with various amounts of cholesterol were
      prepared by the film method and characterised by photon correlation spectroscopy
      and electron paramagnetic resonance (EPR) methods. The transport of the
      hydrophilic spin probe encapsulated in MLV into pig ear skin was investigated by
      EPR imaging methods. The bilayer domain structure was studied by fitting the
      lineshape of the experimental EPR spectra with the spectra calculated by the
      model, which takes into account the heterogeneous structure of the bilayer with
      several coexisting domains. RESULTS: Cholesterol strongly influences the
      entrapped volume of liposomes, the domain structure of the lipid bilayer, and the
      transport of hydrophilic spin probe into the skin. Transport was not observed for
      liposomes composed of phospholipid:cholesterol 1:0 or 9:1 (mol:mol), not even
      above the phase transition temperature from the gel to the liquid crystalline
      phase of DMPC. A significant delivery of hydrophilic spin probe was observed only
      if there was 30 or 50 mol% of cholesterol in the liposome bilayer. CONCLUSIONS:
      It can be concluded that the domain structure of the liposome bilayer is more
      important for the delivery of encapsulated substance into the skin than the
      liquid crystalline phase of the pure phospholipids bilayer.

PMID- 9587947
TI  - Synthesis of a lipophilic daunorubicin derivative and its incorporation into
      lipidic carriers developed for LDL receptor-mediated tumor therapy.
AB  - PURPOSE: Many tumors express elevated levels of LDL receptors (apoB, E receptors)
      on their membranes. Selective delivery of anti-neoplastic drugs to tumors by
      incorporation of these drugs into LDL or LDL-resembling particles should improve
      the efficacy of tumor therapy and minimize the severe side-effects. Since the
      apolipoproteins on the particles are essential for the LDL receptor recognition,
      drugs should preferably be incorporated into the lipid moiety. Most anti-tumor
      agents are too hydrophilic for incorporation into these carriers. METHODS: We
      synthesized LAD, a lipophilic prodrug of daunorubicin, by coupling the drug via a
      lysosomally degradable peptide spacer to a cholesteryl oleate analog. RESULTS:
      The overall yield of the synthesis was 50% with a purity of > 90%. Radioactively
      ([3H]) labeled LAD was obtained via a slightly modified procedure (yield 40%).
      The octanol/water partition coefficient of LAD is 30-fold higher than that of
      daunorubicin. LAD could be incorporated into triglyceride-rich lipid emulsions
      and small liposomes, which, if provided with apoE, have been demonstrated earlier
      to be cleared in vivo via the LDL receptor. The liposomes contained approximately
      10 molecules of LAD per liposomal particle. Analysis of differently sized LAD
      containing emulsions suggests that LAD associates with the surface of lipidic
      particles. In the presence of human serum, LAD did not dissociate from the
      emulsion particles, indicating a firm association of LAD with the carrier.
      CONCLUSIONS: The coupling of a cholesterol ester analog to daunorubicin results
      in a lipophilic prodrug that can be firmly anchored into lipidic carries. LAD
      loaded emulsions and liposomes provided with recombinant apoE will be tested in
      the near future for their ability to deliver LAD to tumor tissue in vivo via the
      LDL receptor.

PMID- 9587948
TI  - Phase transformation of a liposomal dispersion into a micellar solution induced
      by drug-loading.
AB  - PURPOSE: Loading a liposomal dispersion with drug may cause a phase
      transformation into a micellar solution. The present contribution presents a
      detailed physicochemical characterization and an overall model which describes
      transformation due to the properties of any drug. METHODS: Characterization of
      liposomal dispersions was obtained by photon correlation spectroscopy (PCS) and
      small angle X-ray scattering (SAXS). Microstructure of colloidal solutions was
      analysed by 31P-NMR and SAXS. RESULTS: At weight ratios of phospholipid to drug
      from 16:1 to 2:1, liposomal dispersions of milky-white appearance and a mean
      particle size of about 200 nm were obtained. From a ratio of phospholipid to drug
      of 1:1 downwards, the systems became nearly transparent. The particle size
      decreased to a value below 25 nm. SAXS also revealed the change of the colloids.
      Down to a ratio of phospholipid to drug of 2:1 the systems were described as
      bilayer-structured. At and below the ratio of 1:1, a mixed micelle was indicated.
      In the 31P-NMR spectra, the transformation is emphasized by both appearance and
      disappearance of signals. A model based on the theory of self-assembly is
      presented which explains the phase transformation due to drug amphiphilicity.
      CONCLUSIONS: We predict that the model presented will hold in general only due to
      the amphiphilic properties of the drug.

PMID- 9587949
TI  - Drug targeting by polyalkylcyanoacrylate nanoparticles is not efficient against
      persistent Salmonella.
AB  - PURPOSE: We have investigated the efficacy of colistin and ciprofloxacin, free or
      bound to polyalkylcyanoacrylate nanoparticles, for the targeting and eradication
      of Salmonella persisting in the organs of the mononuclear phagocyte system.
      METHODS: A model of persistent S. typhimurium infection was developed in C57BL/6
      mice using i.v. inoculation of the plasmid-cured strain C53. RESULTS: In vivo and
      ex vivo experiments showed that the persisting bacteria seem to evolve to a
      nongrowing state during experimental salmonellosis. In vivo treatment with free
      or nanoparticle-bound colistin did not significantly reduce the number of viable
      Salmonella C53, either in the liver or the spleen of infected mice. In contrast,
      in vivo treatment with ciprofloxacin led to a significant decrease of bacterial
      counts in the liver whatever the stage of infection and the form used. However,
      none of the treatments were able to sterilize the spleen or the liver. In ex vivo
      experiments, colistin was only active against bacteria recovered during the early
      phase of infection, whereas ciprofloxacin exerted its activity at all times
      postinfection. CONCLUSIONS: We suggest that the micro-environment in which the
      bacterial cells persist in vivo probably causes dramatic changes in their
      susceptibility to antimicrobial agents.

PMID- 9587950
TI  - Pegylated nanoparticles from a novel methoxypolyethylene glycol cyanoacrylate
      hexadecyl cyanoacrylate amphiphilic copolymer.
AB  - PURPOSE: The aim of this work was to develop PEGylated poly(alkylcyanoacrylate)
      nanoparticles from a novel methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl
      cyanoacrylate copolymer. METHODS: PEGylated and non-PEGylated nanoparticles were
      formed by nanoprecipitation or by emulsion/solvent evaporation. Nanoparticles
      size, zeta potential and surface hydrophobicity were investigated. Surface
      chemical composition was determined by X-ray photoelectron spectroscopy.
      Nanoparticle morphology was investigated by transmission electron microscopy
      after freeze-fracture. Nanoparticles cytotoxicity was assayed in vitro, onto
      mouse peritoneal macrophages. Cell viability was determined through cell
      mitochondrial activity, by a tetrazolium-based colorimetric method (MTT test).
      Finally, the degradation of PEGylated and non-PEGylated poly(hexadecyl
      cyanoacrylate) nanoparticles was followed spectrophotometrically during
      incubation of nanoparticles in fetal calf serum. RESULTS: Monodisperse
      nanoparticles with a mean diameter ranging between 100 and 200 nm were obtained
      using nanoprecipitation or emulsion/solvent evaporation as preparation
      procedures. A complete physico-chemical characterization, including surface
      chemical analysis, allowed to confirm the formation of PEG-coated nanoparticles.
      The PEGylation of the cyanoacrylate polymer showed reduced cytotoxicity towards
      mouse peritoneal macrophages. Furthermore, the presence of the PEG segment
      increased the degradability of the poly(hexadecyl cyanoacrylate) polymer in
      presence of calf serum. CONCLUSIONS: We succeeded to prepare PEGylated
      nanoparticles from a novel poly(methoxypolyethyleneglycol cyanoacrylate-co
      hexadecyl cyanoacrylate) by two different techniques. Physico-chemical
      characterization showed the formation of a PEG coating layer. Low cytotoxicity
      and enhanced degradation were also shown.

PMID- 9587951
TI  - The preparation of dextran microspheres in an all-aqueous system: effect of the
      formulation parameters on particle characteristics.
AB  - PURPOSE: The purpose of this study was to investigate the effect of the
      formulation parameters on the characteristics of dextran-based microspheres,
      prepared in an all-aqueous system. METHODS: Dextran microspheres were formed by
      polymerization of methacryloyl groups attached to dextran (dexMA), emulsified in
      an aqueous poly(ethylene glycol) (PEG) solution. DexMA/PEG/water phase diagrams
      were established. RESULTS: The binodals in the phase diagrams shifted to higher
      concentrations of dextran and PEG with decreasing molecular weight of both
      polymers, and with increasing degree of MA substitution. The volume-number mean
      diameter of the microspheres, varied between 2.5 and 20 microns. For a given
      formulation, the particle size was independent of the PEG/dexMA volume ratio > 40
      and increased for volume ratios < 40. Furthermore, larger particles were obtained
      with decreasing viscosity of the continuous phase and increasing viscosity of the
      discontinuous phase. CONCLUSIONS: Particle characteristics of dextran
      microspheres prepared in an all-aqueous system, among which the size and initial
      water content, can be tailored by adjusting the formulation parameters.

PMID- 9587952
TI  - Protein deposition from dry powder inhalers: fine particle multiplets as
      performance modifiers.
AB  - PURPOSE: To evaluate the use of carrier-based dry powder aerosols for inhalation
      delivery of proteins and examine the effect of fine particle excipients as
      potential formulation performance modifiers. METHODS: Bovine serum albumin (BSA)
      was co-processed with maltodextrin by spray-drying to produce model protein
      particles. Aerosol formulations were prepared by tumble mixing protein powders
      with alpha-lactose monohydrate (63-90 microns) or modified lactoses containing
      between 2.5 and 10% w/w fine particle lactose (FPL) or micronised polyethylene
      glycol 6000. Powder blends were characterised in terms of particle size
      distribution, morphology and powder flow. Formulation performance in Diskhaler
      and Rotahaler devices was investigated using a twin stage impinger operating at
      60.s51 min-1. RESULTS: Inhalation performance of binary ordered mixes prepared
      using BSA-maltodextrin and lactose (63-90 microns) was improved by addition of
      FPL and micronised PEG 6000. For the addition of 5% w/w FPL the protein fine
      particle fraction (0.5-6.4 microns) using the Diskhaler was increased from 31.7
      +/- 2.4% to 47.4 +/- 2.2%. Inclusion of FPL and micronised PEG 6000 changed the
      bulk properties of inhalation powders and reduced powder flow but did not affect
      device emptying. Unexpectedly, improvements in performance were found to be
      independent of the order of addition of FPL to the ternary powder formulations.
      SEM studies revealed that this was probably the result of a redistribution of
      protein particles between the coarse carrier lactose component and added FPL
      during mixing. CONCLUSIONS: Fine particle excipients can be used to improve the
      performance of carrier-based protein dry powder aerosols. Mechanistically,
      enhancement of performance is proposed to result from a redistribution of protein
      particles from coarse carrier particles to the fine particle component in the
      ternary mix.

PMID- 9587953
TI  - Blood-brain barrier equilibration of codeine in rats studied with microdialysis.
AB  - PURPOSE: The purpose of the study was to investigate the distribution of codeine
      across the blood-brain barrier (BBB) in rats by microdialysis (MD). METHODS: Rats
      were administered intravenous infusion of codeine in doses of (1) 10 mg/kg, (2)
      20 mg/kg for 10 min, and (3) an exponential infusion for 2 h aiming at a plasma
      concentration of 2500 ng/ml, in a crossover design (n = 6). Microdialysis was
      used to determine codeine unbound concentrations in blood and brain extracellular
      fluid (ECF). Total brain tissue and plasma concentrations were also determined.
      Nalorphine was used as a calibrator for measurement of in vivo recovery. RESULTS:
      Relative recovery and retrodialysis loss of codeine and nalorphine were similar
      both in vitro and in vivo. Codeine was rapidly transported into the brain ECF
      with identical influx and efflux clearance across the BBB. The AUC ratios of
      brain to blood were 0.99 +/- 0.25 and 0.95 +/- 0.16 for Dose 1 and 2,
      respectively. The Css ratio of brain to blood was 1.06 +/- 0.12 for the
      exponential infusion. The half-lives were 25 +/- 4 min, 22 +/- 2 min in blood and
      27 +/- 5 min, 25 +/- 5 min in brain for Dose 1 and Dose 2, respectively. Total
      brain tissue concentrations were 3.6 +/- 1.2-fold higher than the unbound
      concentrations in brain. Codeine was demethylated to morphine with an unbound
      AUCblood,morphine/AUCblood,codeine ratio of 7.7 +/- 5.1% in blood. No morphine
      was detected in brain MD, but total concentrations were possible to measure.
      CONCLUSIONS: Codeine rapidly reached a distributional equilibrium with equal
      unbound concentrations in blood and brain. The brain transport of codeine did not
      show any dose-dependency.

PMID- 9587954
TI  - Combined use of carboxyl-directed protein pegylation and vector-mediated blood
      brain barrier drug delivery system optimizes brain uptake of brain-derived
      neurotrophic factor following intravenous administration.
AB  - PURPOSE: Peptide drug delivery to the brain requires optimization of (a) plasma
      pharmacokinetics and (b) blood-brain barrier (BBB) permeability. In the present
      studies, plasma pharmacokinetics are improved with protein pegylation and BBB
      transport is facilitated with the use of vector-mediated drug delivery using the
      OX26 monoclonal antibody (MAb) to the rat transferrin receptor, which undergoes
      receptormediated transcytosis through the BBB in vivo. METHODS: A conjugate of
      OX26 and streptavidin (SA), designated OX26/SA, was prepared in parallel with the
      carboxyl-directed pegylation of brain-derived neurotrophic factor (BDNF). A novel
      bifunctional polyethyleneglycol (PEG) was used in which a hydrazide (Hz) was
      attached at one end and a biotin moiety was attached to the other end. This
      allowed for conjugation of BDNF-PEG-biotin to OX26/SA. RESULTS: The brain uptake
      of BDNF-PEG-biotin was increased following conjugation to OX26/SA to a level of
      0.144 +/- 0.004% injected dose per g brain and a BBB permeability-surface area
      product of 2.0 +/- 0.2 microL/min/g. CONCLUSIONS: These studies demonstrate that
      peptide drug delivery to the brain can be achieved with advanced formulation of
      protein-based therapeutics. The formulation is intended to (a) minimize rapid
      systemic clearance of the peptide, and (b) allow for vector-mediated drug
      delivery through the BBB in vivo. Following this dual formulation, the brain
      uptake of a neurotrophin such as BDNF achieves a value that is approximately 2
      fold greater than that of morphine, a neuroactive small molecule.

PMID- 9587955
TI  - Pulmonary bioavailability of a phosphorothioate oligonucleotide (CGP 64128A):
      comparison with other delivery routes.
AB  - PURPOSE: Phosphorothioate antisense oligodeoxynucleotides are promising
      therapeutic candidates. When given systemically in clinical trials they are
      administered via slow intravenous infusion to avoid their putative plasma
      concentration-dependent haemodynamic side-effects. In this study, we have
      evaluated alternative parenteral and non-parenteral administration routes which
      have the potential to enhance the therapeutic and commercial potential of these
      agents. METHODS: The delivery of CGP 64128A by intravenous, subcutaneous, intra
      peritoneal, oral and intra-tracheal (pulmonary) routes was investigated in rats
      using radiolabelled compound and supported by more specific capillary gel
      electrophoretic analyses. RESULTS: Intravenously administered CGP 64128A
      exhibited the rapid blood clearance and distinctive tissue distribution which are
      typical for phosphorothioate oligodeoxynucleotides. Subcutaneous and
      intraperitoneal administration resulted in significant bioavailabilities (30.9%
      and 28.1% over 360 min, respectively) and reduced peak plasma levels when
      compared with intravenous dosing. Administration via the gastrointestinal tract
      gave negligible bioavailability (< 2%). Intra-tracheal administration resulted in
      significant but dose-dependent bioavailabilities of 3.2, 16.5 and 39.8% at 0.06,
      0.6 and 6.0 mg/kg, respectively. CONCLUSIONS: Significant bioavailabilities of
      CGP 64128A were achieved following subcutaneous, intra-peritoneal and intra
      tracheal administration. Pulmonary delivery represents a promising mode of non
      parenteral dosing for antisense oligonucleotides. The dose-dependent increase in
      pulmonary bioavailability suggests that low doses may be retained in the lungs
      for local effects whereas higher doses may be suitable for the treatment of a
      broader spectrum of systemic diseases.

PMID- 9587956
TI  - Species differences of serum albumins: III. Analysis of structural
      characteristics and ligand binding properties during N-B transitions.
AB  - PURPOSE: The aim of this study was to investigate the characteristics of the
      structural transitions and changes in ligand binding properties of different
      albumins during the pH-dependent structural transition, often referred to as the
      N-B transition. METHODS: Structural transitions were evaluated by means of
      spectrometry, differential scanning calorimetry and chemical modification. In
      addition, ligand binding properties were investigated using typical site-specific
      bound drugs (warfarin, phenylbutazone, ibuprofen and diazepam). RESULTS:
      Conformational changes, including N-B transition, clearly occurred in albumins
      from all species used in this study. The conformational stabilities of all the
      albumins were clearly lost in the weakly alkaline pH range. This was probably the
      result of the destruction of salt bridges between domain I and domain III in the
      albumin molecule. In addition, the profiles of the ANS-induced fluorescence were
      different and could be classified into two patterns, suggesting that hydrophobic
      pockets in the albumin molecules were different for the different species. The
      data suggest that the amino acid residues responsible for the transitions were
      some of the His residues located in domain I. Further, the ligand binding
      properties of the albumins were slightly different but statistically significant.
      CONCLUSIONS: The overall mechanisms of the N-B transition may be similar for all
      the albumins, but its impact is considerably different among the species in terms
      of both structural characteristics and ligand binding properties. Furthermore,
      the transitions appear to be multi-step transitions.

PMID- 9587957
TI  - Effect of GF120918, a potent P-glycoprotein inhibitor, on morphine
      pharmacokinetics and pharmacodynamics in the rat.
AB  - PURPOSE: The objective of this study was to evaluate the effect of a potent P-gp
      inhibitor, GF120918, on the systemic pharmacokinetics and antinociceptive
      pharmacodynamics of a single intravenous dose of morphine in rats. METHODS: Male
      Sprague-Dawley rats received either 500 mg base/kg/d GF120918 or vehicle for 4
      days by gavage, or no pretreatment. On day 4, morphine was administered as a 1-
      or 2-mg/kg i.v. bolus. Antinociception, expressed as percent of maximum possible
      response (%MPR), was evaluated over 300 min after morphine administration. Serial
      blood samples were collected and analyzed for morphine and morphine-3-glucuronide
      (M3G) by HPLC. RESULTS: Morphine clearance and distribution volume were not
      altered significantly by GF120918. M3G AUC in the GF120918-treated rats was
      approximately 2-fold higher than in vehicle-treated rats. For both morphine
      doses, %MPR and the area under the effect-time curve at 300 min were
      significantly higher in the GF120918-treated rats. A
      pharmacokinetic/pharmacodynamic effect model accurately described the effect
      concentration data for the rats that received 1-mg/kg morphine; ke0 was
      significantly smaller for GF120918- vs. vehicle-treated and control rats (0.060
      +/- 0.028 vs. 0.228 +/- 0.101 vs. 0.274 +/- 0.026 min-1, p = 0.0023). EC50 and
      gamma were similar between treatment groups. CONCLUSIONS: Pretreatment with
      GF120918 enhanced morphine antinociception, as assessed by the hot-lamp tail
      flick assay, and elevated systemic M3G concentrations in rats. The differential
      pharmacologic response to morphine in the GF120918-treated animals could not be
      attributed to alterations in systemic morphine pharmacokinetics.

PMID- 9587958
TI  - Bisphosphonates and tetracycline: experimental models for their evaluation in
      calcium-related disorders.
AB  - PURPOSE: This work was aimed at synthesizing novel bisphosphonates (BPs) and
      examining them in comparison to clinically used BPs such as pamidronate and
      alendronate, and to tetracycline, in order to evaluate their potential as
      anticalcification and antiresorption agents. The correlation between the various
      models was examined in order to establish facile experimental models for pre
      screening of potential compounds. METHODS: Nitrogen-containing heterocyclic,
      novel BPs such as 2-(3-methylimidazolio) ethylidene-1,1-bisphosphonic acid
      betaine (VS-5b), 2-(2-dimethylamino-4-pyrazinio)ethylidene-1,1-bisphosphonic acid
      betaine (VS-6b), and 2-(2-alpha-pyridylethylthio) ethylidene-1,1-bisphosphonic
      acid (ISA-225), were synthesized and evaluated in comparison to clinically used
      BPs, in various experimental models of resorption and calcification. RESULTS: The
      physicochemical properties of the novel compounds are slightly different than the
      BPs in clinical use: the pKa values are lower, the affinity for hydroxyapatite is
      lower and the solubilities of the calcium salts are higher. The anticalcification
      potencies of the novel compounds were high and ranked as follows: alendronate =
      pamidronate > VS-6b = VS-5b = ISA-225 > tetracycline. The in vivo antiresorption
      activity of VS-5b and VS-6b in comparison to that of the clinically employed,
      pamidronate, was shown to be similar and higher, respectively. CONCLUSIONS: The
      anticalcification activity of the novel compounds as well as that of tetracycline
      was lower than that of alendronate. The antiresorption activity of VS-6b was
      similar to that of pamidronate. A good correlation between the different models
      was found, enabling the facile screening of novel compounds. The activities of
      tetracycline and EDTA highlight the distinct behavior of BPs as "crystal poison."
      In addition, tetracycline was found to be a potent anticalcification agent in the
      ectopic calcification model.

PMID- 9587959
TI  - Novel pharmacokinetic modelling of transdermal nitroglycerin.
AB  - PURPOSE: To construct a pharmacokinetic (PK) model and to determine population PK
      parameters of nitroglycerin (GTN), 1,2-dinitroglycerin (1,2-GDN), and 1,3
      dinitroglycerin (1,3-GDN). METHODS: Data were obtained in thirty healthy
      volunteers following a single dose of a GTN reservoir transdermal patch. Blood
      samples were obtained just before and at 0.5, 1, 2, 3, 4, 6, 8, 12, 14, and 24
      hours after the patch application and 1 hour after its removal. GTN, 1,2-GDN, and
      1,3-GDN concentrations were determined using HPLC and simultaneously best fitted
      using a first-pass mixed-order release one-compartment PK model. Individual
      estimates (ADAPT-II) were used as priors for a population PK analysis (IT2S).
      Fitted parameters included the percentage (A) of the nitroglycerin dose reaching
      the systemic circulation that was released from the patch by a first-order
      process (K1); two absorption (ka1 and ka2), two metabolite formation (kf1 and
      kf2) and one metabolite elimination (k(m)) rate constants; and three volumes of
      distribution Vc/F, V2/F and V3/F. RESULTS: Nitroglycerin mean population
      parameter estimates and inter-individual variability (CV%) were: A 35% (65), K1
      0.06 h-1(91), ka1 5 h-1(46), ka2 0.47 h-1(39), kf1 11 h-1(42), kf2 0.6 h-1(34),
      k(m) 1.4 h-1(29), V0/F 6 L(31), V2/F 73 L(34), and V3/F 23 L(29). The average
      elimination half-lives for GTN and the two metabolites were 5 and 32 minutes,
      respectively. CONCLUSIONS: The proposed PK model fitted observed concentrations
      of GTN, 1,2-GDN and 1,3-GDN very well. This model should be useful to predict
      drug and metabolite concentrations and to assess bioequivalence of two
      transdermal formulations.

PMID- 9587960
TI  - Application of fractal kinetics for carrier-mediated transport of drugs across
      intestinal epithelial membrane.
AB  - PURPOSE: Fractal kinetics was used for the analysis of the carrier-mediated
      transport for drugs across the intestinal epithelial cells. METHODS: The
      transport was examined under various agitation rates using a monolayer of Caco-2
      cells and rabbit ileum sheets. RESULTS: The passive transport of antipyrine
      across Caco-2 cells was increased with the increasing rate of agitation and was
      supposed to be caused by a change in the thickness of the unstirred water layer.
      On the contrary, in the case of L-lactic acid transport, which follows a carrier
      mediated transport mechanism, the more the agitation rate controlling the fractal
      dimension was increased, the more the permeability rate across the Caco-2 cells
      was decreased. Fractal kinetic analysis of L-lactic acid transport indicated that
      the permeability was caused by a single saturable process. Similar agitation
      effects with L-lactic acid transport were observed in the transport of
      phenylalanine and cephradine in Caco-2 cells. However, the permeability rates of
      benzoic acid and 3-O-methyl-D-glucose across Caco-2 cells and L-lactic acid
      transport across the rabbit ileum tissue indicated the maximum levels at a
      designated agitation rate. This phenomenon was likely to be caused by the
      agitation effects controlling not only the fractal environment but also the
      unstirred water layer. CONCLUSIONS: Carrier-mediated transports are well defined
      by fractal kinetics rather than classical kinetic analysis. Fractal kinetics are
      one of the important areas for understanding and confirming the properties of a
      carrier-mediated transport process.

PMID- 9587961
TI  - Species differences in stereoselective hydrolase activity in intestinal mucosa.
AB  - PURPOSE: The aim of this study is to investigate species differences in the
      stereoselective hydrolysis for propranolol ester prodrugs in mammalian intestinal
      mucosa and Caco-2 cells. METHODS: Hydrolase activities for propranolol prodrugs
      and p-nitrophenylacetate in man (age: 51-71 years), the beagle dog (age: 4 years)
      and Wistar rat (age: 8 weeks) intestinal mucosa, and also in Caco-2 cells
      (passage between 60-70) were estimated by determining the rate of production of
      proparanolol and p-nitrophenol, respectively. RESULTS: The hydrolase activities
      for both propranolol prodrugs and p-nitrophenylacetate were in the order of man >
      rat >> Caco-2 cells > dog for intestinal microsomes, and rat > Caco-2 cells = man
      > dog for intestinal cytosol. Dog microsomes showed stereoselective hydrolysis
      for propranolol prodrugs, but not those from human or rat. Interestingly, both
      subcellular fractions of Caco-2 cells showed remarkable R-enantioselectivity
      except acetyl propranolol. Enzyme kinetic experiments for each enantiomer of
      butyryl propranolol in microsomes revealed that dog possesses both low and high
      affinity hydrolases. Both Km and Vmax values in rat were largest among examined
      microsomes, while Vmax/Km was largest in man. Finally, it was shown that the
      carboxylesterases might contribute to the hydrolysis of propranolol prodrug in
      all species by inhibition experiments. CONCLUSIONS: The hydrolase activities for
      propranolol prodrugs and p-nitrophenylacetate in intestinal mucosa showed great
      species differences and those in human intestine were closer to those of rat
      intestine than dog intestine or Caco-2 cells.

PMID- 9587962
TI  - In vitro methionine oxidation of recombinant human leptin.
AB  - PURPOSE: To investigate the role and importance of the four methionines in
      recombinant human leptin, and the effect of methionine oxidation in leptin
      structural stability and biological activity. METHODS: Oxidized leptin
      derivatives were prepared in the presence of H2O2 and t-butylhydroperoxide,
      separated by RP-HPLC, and characterized by peptide mapping and LC/MS. Their
      biophysical and biological properties were studied. RESULTS: Six major species of
      oxidized leptins were detected: two mono-oxidized, one di-oxidized, two tri
      oxidized, and one tetra-oxidized. Further oxidation at cystine disulfide was also
      detected. Kinetic analysis indicated that oxidation at Met1 and Met69 proceeded
      first and independently. In 48 mM t-butylhydroperoxide, the pseudo first-order
      rate constants, k1 and k69, were 1.5 x 10(-3) and 2.3 x 10(-4) min-1. No change
      in the secondary or tertiary structure was detected for Met1 mono-oxidized and
      Met1, Met69 di-oxidized leptins. The Met1 mono-oxidized leptin retained full
      potency as compared to native leptin. A slight decrease of thermostability and a
      significant loss of the in vitro bioactivity were observed for Met1, Met69 di
      oxidized leptin. Both Met55 and Met137 were not oxidized in t-butylhydroperoxide
      but only in H2O2. They appeared to be much less accessible to oxidation and might
      interact with the hydrophobic core structure of the leptin molecule. CONCLUSIONS:
      The oxidation of leptin occurred in the order of Met1 > Met69 >> Met55
      approximately Met137, and the importance for maintaining leptin structural
      integrity was Met55 approximately Met137 >> Met69 approximately Met1. Met69, but
      not Met1, plays a critical role in the protein stability and activity.

PMID- 9587963
TI  - Structural and functional differences between glycosylated and non-glycosylated
      forms of human interferon-beta (IFN-beta).
AB  - PURPOSE: Two recombinant IFN-beta products have been approved for the treatment
      of multiple sclerosis, a glycosylated form with the predicted natural amino acid
      sequence (IFN-beta-1a) and a non-glycosylated form that has a Met-1 deletion and
      a Cys-17 to Ser mutation (IFN-beta-1b). The structural basis for activity
      differences between IFN-beta-1a and IFN-beta-1b, is determined. METHODS: In vitro
      antiviral, antiproliferative and immunomodulatory assays were used to directly
      compare the two IFN-beta products. Size exclusion chromatography (SEC), SDS-PAGE,
      thermal denaturation, and X-ray crystallography were used to examine structural
      differences. RESULTS: IFN-beta-1a was 10 times more active than IFN-beta-1b with
      specific activities in a standard antiviral assay of 20 x 10(7) IU/mg for IFN
      beta-1a and 2 x 10(7) IU/mg for IFN-beta-1b. Of the known structural differences
      between IFN-beta-1a and IFN-beta-1b, only glycosylation affected in vitro
      activity. Deglycosylation of IFN-beta-1a produced a decrease in total activity
      that was primarily caused by the formation of an insoluble disulfide-linked IFN
      precipitate. Deglycosylation also resulted in an increased sensitivity to thermal
      denaturation. SEC data for IFN-beta-1b revealed large, soluble aggregates that
      had reduced antiviral activity (approximated at 0.7 x 10(7) IU/mg).
      Crystallographic data for IFN-beta-1a revealed that the glycan formed H-bonds
      with the peptide backbone and shielded an uncharged surface from solvent
      exposure. CONCLUSIONS: Together these results suggest that the greater biological
      activity of IFN-beta-1a is due to a stabilizing effect of the carbohydrate on
      structure.

PMID- 9587964
TI  - Isolation and identification of peptide degradation products of heat stressed
      pramlintide injection drug product.
AB  - PURPOSE: This report summarizes the identification of nine deamidation and four
      hydrolysis products from a sample of pramlintide injection final drug product
      that was subjected to stress at 40 degrees C for 45 days. METHODS: The
      pramlintide degradation products were isolated by strong cation exchange HPLC
      followed by reversed-phase HPLC. Subsequent to isolation, the molecular weight of
      each component was determined by liquid chromatography-mass spectrometry (LC/MS).
      Further characterization was accomplished by amino acid sequence analysis and/ or
      enzymatic (thermolysin) digestion followed by LC/MS and sequence analysis.
      RESULTS: The isolated products were identified as [iso-Asp21]-pramlintide, [iso
      Asp3]-pramlintide, and [iso-Asp22]-pramlintide, the deamidation products of
      pramlintide with rearrangement at Asn21, Asn3, and Asn22, respectively. Also
      found were [Asp/iso-Asp14]-pramlintide, and [Asp/iso-Asp35]-pramlintide, the
      deamidation products at Asn14, and Asn35, and [Asp21]-pramlintide together with
      [Asp22]-pramlintide. For the deamidations at the 14th and 35th residues, it could
      not be determined whether the substance corresponded to the Asp or the iso-Asp
      product. The [Asp21] and [Asp22] products could not be separated from each other
      chromatographically but were both identified in a single fraction. Two minor
      degradation products were also identified as deamidated species. However, the
      sites of deamidation remain unknown. Also identified were [1-18]-pramlintide, [1
      19]-pramlintide, [19-37]-pramlintide, and [20-37]-pramlintide, the products of
      hydrolytic peptide backbone cleavage at amino acids His18/Ser19 and Ser19/Ser20,
      respectively. One other product was isolated and tentatively identified as a
      cyclic imide intermediate preceeding deamidation. CONCLUSIONS: The primary mode
      of thermally induced degradation for this peptide is deamidation. A second
      degradation mechanism is peptide backbone hydrolysis.

PMID- 9587965
TI  - Pharmacologically induced embryonic dysrhythmia and episodes of hypoxia followed
      by reoxygenation: a common teratogenic mechanism for antiepileptic drugs?
AB  - Antiepileptic drugs (AEDs), such as phenytoin (PHT), carbamazepine (CBZ),
      trimethadione (TMD), and phenobarbital (PB), have all been associated with a
      similar pattern of malformations, as well as growth retardation and developmental
      delay. Valproic acid (VPA) has been associated with a different pattern of
      malformations. Recent studies suggest that PHT's fetal adverse effect is related
      to its membrane stabilizing pharmacological properties (blockage of voltage
      dependent ion channels). During a restricted sensitive period, this results in
      induction of concentration-dependent bradyarrhythmia in the embryo and episodes
      of hypoxia/reoxygenation. The aim of this study was to compare the potential of
      PHT, CBZ, PB, TMD, and dimethadione (DMD; the active metabolite of TMD) to cause
      bradyarrhythmias. All of these AEDs exert mainly their pharmacological effect via
      blockage of ion channels. VPA and vigabatrin (VGB), which are pharmacologically
      active mainly by other mechanisms, were also tested. C57 Bl/6J mouse embryos were
      cultured in vitro on gestation day 10 in vitro (in 20% rat serum). The drugs were
      suspended in either water or dimethylsulfoxide and administered into the culture
      medium in increasing concentrations up to 20 times the human therapeutic plasma
      concentration. A scoring system was employed in order to rank the drugs based on
      their potential to cause bradycardia, ventricular arrhythmia, and cardiac arrest
      in relation to human therapeutic concentrations. Based on this system, the drugs
      were ranked as follows: DMD = PHT >> PB = CBZ > TMD = VPA >> VGB (no potential).
      The results correlate well with the available clinical/experimental data of the
      tested AED's potential to induce hypoxia-related fetal adverse effects, such as
      oral clefts, distal limb defects, growth retardation, and developmental delay.
      The results support the idea that adverse fetal effects after in utero exposure
      to PHT, PB, CBZ, and TMD (via the active metabolite DMD) are initiated via a
      common pharmacological mechanism: blockage of ion channels in the developing
      heart in the early embryo resulting in bradyarrhythmias, hemodynamic alterations,
      and hypoxia/reoxygenation damage.

PMID- 9587966
TI  - Does aluminum exposure of pregnant animals lead to accumulation in mothers or
      their offspring?
AB  - There is concern that environmental and dietary aluminum (Al) might cause
      developmental toxicity. To better understand this concern, we reviewed published
      studies which administered Al compounds to pregnant animals and measured
      accumulation of Al in mother, fetus, or born offspring. A total of 7 studies were
      identified which administered Al during gestation and evaluated fetal
      accumulation. Another 7 studies administered Al at least until birth and then
      evaluated accumulation in mothers and/or pups. These 14 studies included 4
      different Al compounds (hydroxide, chloride, lactate, and citrate) administered
      by 4 different routes (gavage, feed, intraperitoneal injection, and subcutaneous
      injection) with total doses ranging from 13.5 to 8,400 mg/kg. Fetal Al levels
      were not increased in 6 of 7 studies and pup Al levels were not increased in 4 of
      5 studies in which they were measured. Maternal Al levels were increased in some
      studies, but there was no consistent pattern of organ-specific accumulation and
      several positive studies were contradicted by subsequent reports from the same
      laboratory. Placental levels were increased in 6 of 9 studies and were greater
      than corresponding fetal levels. The weight of evidence in these studies suggests
      that environmental and dietary Al exposures are unlikely to pose risks of Al
      accumulation to pregnant animals or their fetuses.

PMID- 9587967
TI  - Teratogenic effects of implanting fibroblast growth factor-2-soaked beads in the
      cardiac region of the stage 24 chick embryo.
AB  - The identification of fibroblast growth factor-2 (FGF-2), and other family
      members, in a variety of embryonic tissue extracts has implicated these growth
      factors as participants in many embryonic events, including cardiogenesis. The
      present study was conducted in an attempt to characterize the effects of
      exogenous FGF-2 on the development of the avian heart. Heparin acrylic beads,
      each soaked in 100 micrograms/ml FGF-2, were applied to the Hamburger and
      Hamilton [(1951) J. Morphol. 88:49-92] stage 24 (day 4 of incubation) chick
      heart, near the primitive ventricle. The embryos were allowed to develop until
      stage 41 (day 15), at which time they were observed for the presence of gross
      external and internal anomalies. Crown rump length (CRL), wet weight (WW), and
      various heart measurements were obtained and compared. The survival rate of the
      control group was significantly higher (P < 0.05) than that for the experimental
      group and the anomaly rate for the control group was significantly lower (P <
      0.01) than that for the experimental group. The experimental group exhibited a
      wide range of anomalies, most of which were cardiac in nature; however, anomalies
      of the ventral thoracoabdominal wall were also noted. Our data suggest that
      application of exogenous FGF-2 has teratogenic effects on cardiac development as
      well as on the development of the ventral body wall of the avian embryo.

PMID- 9587968
TI  - Difference in sensitivity of inner cell mass and trophectoderm to X-irradiation
      in mouse blastocysts.
AB  - Pregnant B6C3F1 mice were exposed to a single whole body X-irradiation on day 4
      (73-74 hr postconception) of gestation. In experiment 1, they were sacrificed at
      2, 4, 6, or 9 hr after a dose of 2 Gy, and their embryos were removed and
      examined with light and electron microscopy. In experiment 2, dose-response
      effects of irradiation on the embryos were examined 4 hr after doses of 0-4 Gy.
      In experiment 3, DNA fragmentation (a marker of apoptosis) was observed by 3'-OH
      nick-end labeling technique. In inner cell mass (ICM) and trophectoderm (TE) of
      blastocysts exposed to 2 Gy, cells with cytoplasmic degeneration, or dead cells
      phagocytosed by their neighboring cells, were found. Although morphological
      features of these dying cells did not reveal typical characteristics of apoptosis
      such as nuclear condensation and membrane blebbing, DNA fragmentation was
      detected by nick-end labeling technique. The degenerated cytoplasm consisted of
      aggregating ribosomes. Degenerated cells began to increase from 2 hr after
      irradiation and reached maximal at 4 hr in both ICM and TE. The incidences of
      degenerated cells in ICM were higher than those in TE at any time point. These
      findings provide evidence that cell death observed in blastocysts after X
      irradiation is apoptotic and sensitivity of the two groups of cells (ICM and TE)
      to X-rays is different.

PMID- 9587969
TI  - [Case study. Sudden death due to acute cecal colitis after unilateral ovariectomy
      in a horse].

PMID- 9587970
TI  - [Disorders in trace element status in cattle from the view of herd supervision.
      1: Classical trace elements].
AB  - In a bipartite review the current knowledge about trace elements in cattle is
      described. The first part contains the classical trace elements iron, zinc,
      copper, manganese, molybdenum, iodine, selenium, cobalt, chromium and fluorine.
      For each trace element the following aspects are illustrated: physiological
      function, factors leading to deficiency or over-supply, symptoms of deficiency
      and poisoning and the diagnostic.

PMID- 9587971
TI  - [Behavioral response of cows after intrauterine application of disinfectants for
      treatment of endometritis].
AB  - Seventy-five animals were investigated in an attempt to study the chronological
      process of response to vaginal irritation by application of disinfectants for
      endometritis therapy. Aqueous peracetic acid solutions and Lugol solution were
      used. Cows reacted to intrauterine application of disinfectant drugs with tail
      lifting, pressing and sometimes groaning as expression of pain. We tried to
      quantify this response by registration of these different signs longer than two
      hours after treatment. The responses are caused by reflux of solution from the
      uterus into the vagina. They were different and depending on reflux volume, used
      drugs and their concentration. In comparison to peracetic acid solutions, the
      application of Lugol with 0.5% iodine seemed to induce a more intensive response
      to application.

PMID- 9587972
TI  - [Squamous cell carcinoma of the claw matrix in a cow].
AB  - Clinical, radiographic, gross-pathological and histological findings in a
      squamous cell carcinoma of the claw matrix in a three-year-old Simmental cow are
      described. The cow showed severe lameness of the right foreleg. Radiological
      examination revealed a large osteolytic focus in the medial distal phalanx. The
      tentative clinical diagnosis of apical pedal bone necrosis was followed by
      amputation and pathological examination of the claw. The horn capsule showed no
      lesions. Pathological examination revealed soft consistency of pedal bone and the
      cut surface showed a yellowish crumbling material, which had replaced most of the
      pedal bone. Histologically, infiltration and osteolysis of distal pedal bone by a
      squamous cell carcinoma was ascertained. This claw tumor has not been reported
      until now. Clinically, it resembles apical pedal bone necrosis and therefore
      should be included in the differential diagnosis.

PMID- 9587973
TI  - [Clinical and laboratory diagnostic findings in chronic pleuropneumonia of
      swine].
AB  - In the course of an experimental study 12 pigs were infected intrabronchially
      with the pathogen of infectious porcine pleuropneumonia, Actinobacillus
      pleuropneumoniae. All animals survived the acute stage of infection due to the
      application of subtherapeutic doses of antibiotics. After infection all of the
      animals showed clinical signs of acute pneumonia with an elevation of body
      temperature to about 41 degrees C. Bronchoalveolar lavage fluid (BALF) was taken
      every week endoscopically. An increase of neutrophil granulocytes could be
      observed at day 7 and 14 after infection. In parallel, a clear granulocytosis and
      a shift to the left of the nuclei was observed at day 7. Comparing the methods
      for detection of Actinobacillus pleuropneumoniae serological assays like the
      complement-fixation assay (CFA) and enzyme-linked immunosorbent assay (ELISA) as
      well as immunofluorescence in lung tissue and BALF were more sensitive than
      cultural isolation from lung tissue, tonsils and BALF.

PMID- 9587974
TI  - [Contribution to the treatment of displacement of the ascendant colon in the
      spleen-kidney area].
AB  - Objective to this field study was to find an alternative to rolling a colic
      patient with left dorsal displacement under general anesthesia. For that purpose
      a total of 49 horses with a complete nephrosplenic entrapment out of 542 colic
      patients presented at the Tierklinik Kerken in 1996 were retrospectively
      evaluated. Having performed a preliminary colic examination and initial treatment
      if needed, horses which did not undergo surgery immediately where left loose in a
      small sized arena to move and roll themselves under observation. According to the
      results of further exams, horses were left in the arena until the displacement
      was corrected and were only treated if needed or underwent surgery. In 42 (85.7%)
      out of the 49 horses that were sent in for left dorsal displacement, the
      entrapment resolved itself within a period of 30 minutes to 48 hours (phi 12.1 +/
      10.4 hours) through walking and rolling themselves. Seven horses (14.3%) needed
      surgery (midline laparotomy) due to worsening of the general condition, repeated
      overload of the stomach or more dramatic colic symptoms. Two horses (4.1%)
      developed a gastroduodenojejunitis or thyphlocolitis postoperatively and were
      euthanized. The results showed that individual rolling of colic patients versus
      rolling under general anesthesia as a means of therapy in cases of nephrosplenic
      entrapment has higher success rates and also reduces the risk for the horses as
      no general anesthesia is necessary.

PMID- 9587975
TI  - [Investigations on hematologic and clinical chemical parameters in blood serum of
      newborn fallow deer calves (Dama dama L.). 1: Birth weight and hematologic
      parameters].
AB  - 59 newborn fallow deer calves were caught, marked, clinically investigated and
      weighed within 24 hours after parturition. Simultaneously a blood sample was
      taken from the jugular vein for hematological investigation. Mean birth weight
      was 4.84 +/- 0.4 kg. Mean number of erythrocytes was 8.91 +/- 0.77 T/l, the
      hemoglobin concentration was 8.28 +/- 0.77 mmol/l and the PCV was 40.9 +/- 3.0%.
      A temporary physiological erythropenia as described for neonates of different
      species during early postnatal development was not found in newborn fallow deer
      calves. On the other hand the fallow deer calves were born with a remarkable
      little number of leukocytes (4.5 +/- 1.34 G/l). Granulocytes are dominant among
      the white blood cells in newborn and adult fallow deer. Only during the 3rd and
      4th month of life the number of lymphocytes raised temporarily.

PMID- 9587976
TI  - [Reovirus infection of pheasants (Phasianus colchicus)].
AB  - In this case report we discribe clinic, pathology and diagnostic of an avian
      reovirus-infection in pheasants. The disease was observed 1993 in a flock of game
      pheasants in the western part of Turkey. Of a live-stock of 100 animals, 27 were
      affected most of them being three to five months old. Beside a general disorder,
      sick pheasants showed signs of shortness of breath as well as greenish, watery
      diarrhoea and died within a week. The pathologic findings were dominated by an
      extreme hepatopathia. In addition a fibrinous tracheitis, a catarrhal
      inflammation of the gut and a perihepatitis fibrinosa could be observed. From
      organs of affected pheasants a pathogen could be isolated, which was
      characterized anti-genetically, by physico-chemical properties an by
      electronmicroscopy as avian reovirus.

PMID- 9587977
TI  - [Hazardous materials and work safety in veterinary practice. 1: Hazardous
      material definition and characterization, practice documentation and general
      rules for handling].
AB  - In the last years the standards for professional handling of hazardous material
      as well as health and safety in the veterinary practice became considerably more
      stringent. This is expressed in various safety regulations, particularly the
      decree of hazardous material and the legislative directives concerning health and
      safety at work. In part 1, a definition based on the law for hazardous material
      is given and the potential risks are mentioned. The correct documentation
      regarding the protection of the purchase, storage, working conditions and removal
      of hazardous material and of the personal is explained. General rules for the
      handling of hazardous material are described. In part 2, particular emphasis is
      put on the handling of flammable liquids, disinfectants, cytostatica, pressurised
      gas, liquid nitrogen, narcotics, mailing of potentially infectious material and
      safe disposal of hazardous waste. Advice about possible unrecognized hazards and
      references is also given.

PMID- 9587979
TI  - [Poisonous snakes of Europe].
AB  - Characteristics of poisonous snakes and their toxines are described. The
      appearance and biology of all European poisonous snakes, eight vipers (family
      Viperidae) and one opisthoglyph colubride snake (family Colubridae) are given in
      detail.

PMID- 9587978
TI  - [Case study. Incidence of uterine adenocarcinoma in a rabbit (report of a case)].

PMID- 9587980
TI  - [Adder bites in humans].
AB  - In Germany the common viper (Vipera berus) and very seldom Vipera aspis are the
      only in freedom normally existing snakes. In general, bites by the common viper
      cause slight local symptoms, sometimes strong swellings of the extremities, but
      only rarely severe perilous general symptoms such as shock and angioneurotic
      edema. Mortal progresses despite of medical treatment are the exceptions. The
      most important therapeutic measure is the immobilization of the bitten extremity
      and the transport in a recumbent position to the next surgeon or clinic. The
      perilous shock and the angioneurotic edema often react on the administration of
      antihistaminica and corticosteroids, whereas the increase of the swelling of the
      extremity cannot be influenced by this treatment. The corresponding antisera have
      an advantageous and fast effect on all general symptoms and seem to favourably
      influence the swelling of the extremities. Because of the allergic reactions
      against the sera from horses, which do not occur seldom, in severe cases only
      Beritab--which is not yet admitted in Germany--with purified Fab-fragment
      antibodies from sheep should be used.

PMID- 9587981
TI  - [Snake bites in dogs].
AB  - Altogether 11 cases of stings in dogs are reported. In at least nine cases,
      common vipers (Vipera berus) were identified to be the causes. The most
      frequently observed symptoms were haemorrhagic and oedematous inflammations of
      the area of the wounds, furthermore haemolysis and intense leukocytosis with
      relative and absolute neutrophilia and in some cases shock symptoms. One dog died
      17 days after the accident from multiple organ insufficiencies, all the other
      dogs improved. As a therapy, bandage of the injured limb, quieting of the dog,
      snake antitoxin, corticosteroids, antihistaminics, antibiotics, and symptomatic
      therapy depending on the clinical signs are recommended.

PMID- 9587982
TI  - [Indirect blood pressure measurement in cats with diabetes mellitus, chronic
      nephropathy and hypertrophic cardiomyopathy].
AB  - In the present study blood pressure was measured in cats comparing two indirect
      methods (oscillometric versus Doppler-sonographic) over a wide pressure range. It
      was shown, that at the lower pressures Doppler and oscillometric measurements
      were basically equivalent. However for higher pressures oscillometric
      measurements were consistently lower than Doppler measurements. This difference
      became greater as blood pressure increased. The determination of blood pressure
      by the Doppler-sonographic method was always possible, whereas the measurement by
      the oscillometric method was often not possible, especially at higher blood
      pressure levels. In a second step, the frequency of hypertension was determined
      in cats with diabetes mellitus, chronic renal failure and hypertrophic
      cardiomyopathy. Eight cats with diabetes mellitus had oszillometric blood
      pressure values of 101-155 mmHg systolic, 42-105 mmHg diastolic and 65-125 mmHg
      mean arterial pressure determined at the front leg and 110-167 mmHg systolic, 44
      98 mmHg diastolic, and 61-125 mean arterial pressure determined at the tail. The
      Doppler-sonographic values were 120-180 mmHg. Only the oscillometric measurement
      (at the tail) of the systolic pressure was significantly higher than that of
      normal cats. In 11 cats with chronic renal failure the following values were
      determined by the oszillometric method: at the front leg 137-182 mmHg systolic,
      74-138 mmHg diastolic, 100-162 mmHg mean arterial pressure and at the tail 134
      189 mmHg systolic, 53-109 mmHg diastolic, 80-135 mmHg mean arterial pressure.
      With the Doppler-sonographic technique the blood pressure was between 120 and 280
      mmHg. All blood pressure measurements were significantly higher than those of
      healthy cats, except the oscillometric measurements of diastolic blood pressure.
      In 12 cats with hypertrophic cardiomyopathy systolic pressure was 108-179 mmHg,
      diastolic pressure was 64-135 mmHg, and mean arterial pressure was 89-154 mmHg at
      the front leg using the oscillometric method. At the tail results were as
      follows: 121-201 mmHg systolic, 61-141 mmHg diastolic, and 85-160 mmHg mean
      arterial pressure. By the Doppler-sonographic technique determined blood pressure
      was 110-260 mmHg. All oscillometric measurements except the diastolic pressure
      determined at the front leg were significantly higher than in normal cats. Four
      cats with chronic renal failure and five cats with hypertrophic cardiomyopathy
      showed retinal hemorrhages and/or detachments. Eight of this nine cats had blood
      pressure measurements above the normal range. We conclude that hypertension can
      be detected in cats with several diseases. In most cases reliable measurements
      can only be obtained by Doppler-sonographic methods.

PMID- 9587983
TI  - [Observations on the side effects after application of non-steroidal anti
      inflammatory agents in dogs].
AB  - This review describes with some examples possible side-effects after oral
      treatment with the non-steroidal anti-inflammatory drug meloxicam in dogs.
      Adverse effects include gastrointestinal and renal irritation such as nausea,
      vomiting and hemorrhagic gastroenteropathy. Therefore in case of long-term
      administration a dose reduction of 50 percent (single dose of 0.2 mg/kg followed
      by 0.1 mg/kg once daily) is recommended in dogs with chronic locomotor disorders.

PMID- 9587984
TI  - [Coat color in dogs. 2: Clinical significance].
AB  - The meaning of the coat colour of the dog reaches further than only to the field
      of breeding for beauty. Besides aspects of destination (hunting dogs, herding
      dogs) the clinical meaning is of particular interest. Some colours can show
      certain defects. Diseases of allowed colours are the colour dilution alopecia
      (CDA) in diluted (mostly "blue") pigmentation with its subtype of Black hair
      follicular dysplasia (BHFD) in black pigmentation and congenital deafness in
      extreme piebalds. Not allowed coat colours, which are connected with defects, are
      the extreme dapple of the Merle-syndrome and the "grey" Collie with cyclic
      hematopoesis.

PMID- 9587985
TI  - [Perioperative anesthesia management in small mammals].
AB  - In anaesthesiology rabbits and rodents are considered being high risk patients as
      about 30% of the anaesthetized patients die intra- or postoperatively. Due to the
      anatomic structures many anaesthetic techniques and patient monitoring are very
      difficult of even impossible to perform in these animals. For this reason
      anaesthesia of rabbits and rodents confronts the veterinarian with great
      problems. The main complications during anaesthesia are discussed and principles
      of the perioperative anaesthetic management, of anaesthetic techniques as well as
      patient monitoring are presented.

PMID- 9587987
TI  - Respiratory ultrasonography of human parasternal intercostal muscle in vivo.
AB  - The parasternal intercostal muscle (PS) is phasically active during inspiration,
      but its mechanical function in humans is poorly understood. The aim of this study
      was to describe PS motion ultrasonographically during respiration. We used a 7.5
      MHz curvilinear phased array transducer to obtain ultrasonograms of the second
      right and left interspace in the sagittal plane, 2-3 cm lateral to the sternum,
      in 4 seated subjects (3M, 1F), during tidal breathing and at residual volume
      (RV), functional residual capacity (FRC) and total lung capacity (TLC). Images
      were recorded on videotape and off-line, digitized, transferred to a workstation,
      and traced manually to outline the external and pleural borders of the PS muscle
      in relation to a rectangle bounded by the second and third ribs. To assess PS
      shape and motion, we measured inter-rib distance (Lics), PS thickness (Tps), and
      motion of the midpoint of the muscle relative to the midpoint of the reference
      rectangle (Mps). We also calculated the average radius of curvature of the
      external and pleural PS borders (Re, Rp) over the mid 50% of Lics, and 1/Re and
      1/Rp. During tidal breathing, Mps moved ventrally by 0.42 +/- 0.06 mm (p = 0.001)
      against the pleural pressure gradient, and 1/Re and 1/Rp decreased by 1.1 x 10(
      2) +/- 1.6 x 10(-3) mm-1 and 8.4 x 10(-3) +/- 1.4 x 10(-3) mm-1, respectively (p
      < 0.001). Lics and Tps did not change (p > 0.19). We conclude that, during
      inspiration, the PS moves ventrally and straightens, and lung volume, neural
      activation and pleural pressure influence PS shape and motion. The findings
      support an intercostal stabilizing function of the PS and suggest a novel
      mechanism by which the PS may contribute to the inspiratory fall in pleural
      pressure.

PMID- 9587986
TI  - [Examination of the lower respiratory tract of Psittacinae and Amazoninae species
      by means of reconstructive transmission computed tomography. 2: Examination of
      parrots with respiratory symptoms].
AB  - To date, the lack of clinical signs, the misjudgement of possible signs and the
      limits of available, diagnostic tools in non-domesticated birds have made the
      diagnosis of respiratory disease in tropic psittacines very difficult. In
      accordance to this, the examinations performed prove that many diseased
      psittacines are diagnostically misjudged. The disease was either not noticed at
      all, or was only noticed in advanced stages when therapy was without success.
      With the use of a non-invasive diagnostic tool--computed tomography--pathological
      alterations in diseased gray parrots and amazons were able to be assessed based
      on anatomical data gained in the previous investigations on healthy birds (see
      part 1). In a next step results gained by CT examinations were compared to those
      obtained by conventional radiography. In contrast to the conventional
      radiography, the CT was able to demonstrate less evident alterations in earlier
      stages of development, thus solving problems of diagnosis which are specific for
      avian medicine. Especially in endangered animals, the use of such a diagnostic
      technique in combination with other conventional methods should be highly
      considered. A quick and early recognition of disease, paving the way for a
      successful therapy, is the fundamental prerequisite for the preservation and
      breeding of endangered species, making it an important, veterinary contribution
      to animal conservation.

PMID- 9587988
TI  - Portal vein pulsatility ratio provides a measure of right heart function in
      chronic heart failure.
AB  - Portal vein flow was recorded by color Doppler sonography in 31 patients with
      chronic heart failure and 18 control subjects. Compared with patients showing a
      forward flow (Group A), those with reversed portal vein flow (Group B) had higher
      prevalence of tricuspid regurgitation (75% vs. 43%), hepatic congestion (100% vs.
      30%) and ascites (50% vs. 18%), and showed higher right atrial pressure (25.3 +/-
      3.01 mmHg vs. 11.8 +/- 5.75 mmHg, p < 0.01). In controls, portal vein pulsatility
      ratio was 0.66 +/- 0.08, in Group A it was 0.46 +/- 0.28 (p < 0.01), in Group B 
      0.60 +/- 0.19 (p < 0.01). Portal vein pulsatility ratio negatively correlated
      with right atrial pressure (r = -0.87; p < 0.01). In Group A, hepatic congestion,
      ascites and tricuspid regurgitation were associated with a higher portal vein
      pulsatility. This study indicates that portal vein pulsatility ratio reflects the
      level of impairment of the right heart.

PMID- 9587989
TI  - Diagnosis and monitoring of middle cerebral artery occlusion with contrast
      enhanced transcranial color-coded real-time sonography in patients with
      inadequate acoustic bone windows.
AB  - Transcranial color-coded real-time sonography (TCCS) is an emerging diagnostic
      technique that allows noninvasive imaging of intracranial vessels within
      parenchymal structures. However, in some patients, transcranial ultrasound is
      particularly hindered by insufficient ultrasound penetration through the temporal
      bone. The present study evaluates whether or not application of an echo-contrast
      agent in ultrasound-refractory patients with middle cerebral artery (MCA) trunk
      occlusion enhances image acquisition enough to yield accurate diagnoses. Contrast
      enhanced (CE) TCCS examinations, computed tomography scans and angiographic
      studies were performed in 20 patients with clinical symptoms suggestive of MCA
      occlusion within 12 h of the onset of symptoms. For comparison, 20 control
      persons without history or clinical signs for cerebrovascular diseases were
      examined using CE-TCCS. In none of the patients or control subjects did
      unenhanced TCCS investigations depict any color-coded vascular signal of an
      intracranial vessel. After application of 9 mL of 400 mg/mL galactose-based
      microbubbles, CE-TCCS was performed. In subjects with MCA occlusion, CE-TCCS
      examinations were repeated within 24 h, 48 h and 5 days after stroke. In stroke
      patients (n = 20), CE-TCCS showed an occluded MCA main stem in 11 patients, and
      this vessel was clearly demonstrable on the unaffected side. On the affected
      side, the posterior cerebral artery (PCA) and anterior cerebral artery (ACA)
      could be visualized in 8 of 11 subjects; in 3 patients, at least 1 of these
      vessels was detectable. Angiographic studies confirmed the diagnosis of MCA trunk
      occlusion in all 11 individuals. In follow-up investigations, 3 stroke patients
      had angiographic and CE-TCCS examinations consistent with vessel reperfusion.
      Nine stroke patients had a patent MCA shown in angiographic and CE-TCCS
      examinations. In the control group, the MCA trunk could be visualized in all
      subjects by CE-TCCS. CE-TCCS is a sensitive and specific ultrasound method for
      the diagnosis of MCA trunk occlusion that overcomes the anatomical hindrance of
      inadequate acoustic bone window. This technique may help to identify patients
      suitable for thrombolytic therapies and monitor their response.

PMID- 9587990
TI  - Evaluation of acoustical parameter sensitivity to age-related and osteoarthritic
      changes in articular cartilage using 50-MHz ultrasound.
AB  - The current study reports the sensitivity of acoustical parameters estimated at
      high frequency to the osteoarthritic morphological and structural changes in
      patellar cartilage in rat knees. Osteoarthritis (OA) was induced by a single
      intra-articular injection of mono-iodo-acetic acid in right knees. OA patellas
      and their contralateral controls were excised at regular intervals after
      injection and were examined in vitro with a scanning acoustical microscope
      operating with a poly(vinylidene di-fluoride) (PVDF) 80-MHz focused transducer.
      Cartilage thickness was estimated using B-scan images. The quantitative analysis
      of the radiofrequency signal backscattered by the cartilage was performed using
      integrated reflection coefficient (IRC) and apparent integrated backscatter
      (AIB), which were estimated in the 20-60-MHz frequency range. One week after
      injection, a cartilage thickness decrease was detected (-6%, on average) that
      preceded the significant hypertrophy (20.1%) that occurred 2 weeks after
      injection and could be due to tissue repair. From 1 week to 3 weeks after
      injection, the IRC of OA patellas was significantly lower than that of control
      patellas. The IRC difference increased with time from -3.3 +/- 2.4 dB at 1 week
      to -8.4 +/- 1.7 dB at 3 weeks. An AIB decrease was observed with time for both OA
      and control patellas (-2.9 to -4.2 dB per week). An AIB difference between OA and
      control patellas was detected from 1 week to 3 weeks after injection. This
      difference decreased with time. IRC variation reflects a change in acoustical
      impedance of the superficial layer of the cartilage and could be linked to a
      change in constituent content and/or to a disruption of fibers of the collagen
      network that led to the fibrillation of the cartilage surface. AIB variation
      reflects a change in shape, size and/or density of the scatterers and could be
      related to changes in the constituent content and in the organization of the
      matrix in the internal layer of the cartilage. IRC and AIB could provide
      information about the structural modifications of the cartilage due to
      osteoarthritis or to cartilage maturation.

PMID- 9587991
TI  - Analysis of linear, area and volume distortion in 3D ultrasound imaging.
AB  - We have developed a three-dimensional (3D) ultrasound imaging system that uses a
      side-firing probe, axially rotated under computer control, to acquire a series of
      2D images, from which the 3D image is reconstructed. For an undistorted
      reconstruction, the inner radius R0 of the 2D images and the total scanning angle
      theta must be known accurately. Here, we describe (a) a theoretical analysis of
      the relative distortion in image shape, length, area, and volume due to an error
      delta R in R0 or delta theta in theta; (b) measurements of these in simulated and
      real 3D images; and (c) a method to calibrate R0, theta, and image scale
      accurately. Theoretically, all four relative distortions vary as P delta R/R + Q
      delta theta/theta, where magnitude of P < or = 1, magnitude of Q < or = 1, and R
      is the average distance of the object from the axis. In every case, the simple
      theoretical formulas for P and Q agree with image measurements to within the
      measurement uncertainty.

PMID- 9587992
TI  - The narrow band hypothesis: an interesting approach for high-intensity transient
      signals (HITS) detection.
AB  - We propose a new approach to detect microemboli automatically using the narrow
      band hypothesis. An initial database of 560 peripheral arterial Doppler high
      intensity transient signals (HITS) was created to study microemboli and to define
      the normal limits to be used in our method. When a HITS occurs, our approach
      consists of modelling the Doppler signal using amplitude and frequency wave
      modulation. A threshold was defined experimentally using this database and then
      applied to 38 recordings from 12 patients. Using another database, six expert
      Doppler users reported 140, 176, 155, 161, 161 and 146 HITS, corresponding to a
      total of 197 different observed HITS. When an event was detected by 6, 5, 4, 3, 2
      and 1 of the observers, the sensitivity of the automatic detection was 94.8%,
      75.9%, 55.6%, 42.9%, 30% and 0%, respectively. The sensitivity of our automatic
      detection thus is highly associated with the likelihood (defined as the ratio of
      observers in agreement to the total number of observers) of an event: r = 0.99
      for p < 0.0001. Although future research would result in improvement of the
      specificity, the narrow band hypothesis appears to be a promising technique for
      the detection of HITS.

PMID- 9587993
TI  - Imaging and spectrum analysis of contrast agents in the in vivo rabbit eye using
      very-high-frequency ultrasound.
AB  - We have conducted initial studies that demonstrated the feasibility of employing
      ultrasonic contrast agents with very-high-frequency ultrasound (VHFU), using
      wideband transducers with center frequencies near 40 MHz. These studies were
      undertaken with an ultimate objective of quantifying perfusion in vessels in the
      eye and other organs. We expanded the model developed by Lizzi et al. (1983) to
      incorporate the scattering characteristics from encapsulated bubbles, such as
      contrast agents. Our analysis shows how the spectral slopes and intercepts
      measured from contrast agents are related to factors that include the radii and
      concentration of contrast-agent particles. We conducted in vitro experiments to
      validate the theoretical predictions and obtained excellent agreement. We
      obtained in vivo VHFU data from the eyes of anesthetized rabbits before and after
      injection of Albunex and Aerosomes. Digitally computed B-mode images demonstrated
      echo enhancement within the ciliary body and its processes. The magnitudes of
      these enhancements were quantified using calibrated spectrum-analysis techniques.

PMID- 9587994
TI  - Advantages of subharmonic over second harmonic backscatter for contrast-to-tissue
      echo enhancement.
AB  - It is shown experimentally that backscatter from two ultrasonic contrast agents
      suspended in water or saline contains subharmonics of the incident frequency that
      are stronger than those backscattered at the same incident pressure from chicken
      breast. It is also shown that the ratio of subharmonic backscattered from
      contrast to that backscattered from tissue, is stronger than the ratio of
      backscattered second harmonic. In consequence, blood that contains contrast
      should be more easily detectable with respect to tissue if the subharmonic,
      rather than the second harmonic, is used for imaging.

PMID- 9587995
TI  - Intravascular ultrasound elastography in human arteries: initial experience in
      vitro.
AB  - Intravascular elastography is a new technique to obtain the local mechanical
      properties of the vessel wall and its pathology using intravascular ultrasound
      (IVUS). Knowledge of these mechanical properties may be useful for guiding
      interventional procedures. An experimental set-up is described for assessment of
      the strain data of arteries. Using a 30-MHz IVUS catheter, radio frequency data
      are acquired with a custom-made high-performance data acquisition system. High
      resolution, local tissue displacement estimation by cross-correlation is followed
      by computation of local strain. An algorithm that uses a priori knowledge of the
      correlation coefficient function was applied to filter the obtained strain data.
      With this experimental set-up, intravascular elastograms containing 400
      angles/revolution with a radial resolution of 200 microns can be produced. The
      feasibility of intravascular elastography with this experimental set-up is
      demonstrated using two diseased human femoral arteries. Qualitative comparison of
      the elastograms with the echograms and the histology demonstrates the potential
      of intravascular elastography to obtain mechanical information from the vessel
      wall and from plaque.

PMID- 9587996
TI  - Elastographic imaging of low-contrast elastic modulus distributions in tissue.
AB  - Elastography is a new ultrasonic imaging technique that produces images of the
      strain distribution in compliant tissues. This strain distribution is derived
      from ultrasonically estimated longitudinal internal motion induced by an external
      compression of the tissue. The displayed two-dimensional (2-D) images are called
      elastograms. In this paper, it is demonstrated that, when signal-to-noise ratio
      enhancing techniques are used, elastography is capable of imaging low-contrast
      elastic modulus tissue structures with high contrast-to-noise ratios. This is
      demonstrated using both computer simulations and data obtained from 3 days
      postmortem ovine kidneys in vitro. The elastograms of such organs suggest that
      the modulus slowly decays from the renal cortex (RC) to the interior of the renal
      sinus (RS). Such modulus variation is corroborated by independent measurements of
      the Young's moduli. It is found that the RC is approximately twice as hard as the
      interior of the RS. We invoke our previous results on elastographic contrast
      transfer efficiency to demonstrate that, at low contrast, the elastogram may be
      interpreted as a quantitative image of the relative Young's modulus distribution.

PMID- 9587997
TI  - Multilevel and motion model-based ultrasonic speckle tracking algorithms.
AB  - A multilevel motion model-based approach to ultrasonic speckle tracking has been
      developed that addresses the inherent trade-offs associated with traditional
      single-level block matching (SLBM) methods. The multilevel block matching (MLBM)
      algorithm uses variable matching block and search window sizes in a coarse-to
      fine scheme, preserving the relative immunity to noise associated with the use of
      a large matching block while preserving the motion field detail associated with
      the use of a small matching block. To decrease further the sensitivity of the
      multilevel approach to noise, speckle decorrelation and false matches, a smooth
      motion model-based block matching (SMBM) algorithm has been implemented that
      takes into account the spatial inertia of soft tissue elements. The new
      algorithms were compared to SLBM through a series of experiments involving manual
      translation of soft tissue phantoms, motion field computer simulations of
      rotation, compression and shear deformation, and an experiment involving
      contraction of human forearm muscles. Measures of tracking accuracy included mean
      squared tracking error, peak signal-to-noise ratio (PSNR) and blinded
      observations of optical flow. Measures of tracking efficiency included the number
      of sum squared difference calculations and the computation time. In the phantom
      translation experiments, the SMBM algorithm successfully matched the accuracy of
      SLBM using both large and small matching blocks while significantly reducing the
      number of computations and computation time when a large matching block was used.
      For the computer simulations, SMBM yielded better tracking accuracies and spatial
      resolution when compared with SLBM using a large matching block. For the muscle
      experiment, SMBM outperformed SLBM both in terms of PSNR and observations of
      optical flow. We believe that the smooth motion model-based MLBM approach
      represents a meaningful development in ultrasonic soft tissue motion measurement.

PMID- 9587998
TI  - The NPL Doppler fetal heart beat detector test facility.
AB  - There are many thousands of Doppler fetal heart beat detectors in medical use and
      many different detector manufacturers but, until recently, there has been no well
      defined quantitative method for measuring the sensitivity of these detectors and,
      therefore, no way of directly comparing their technical performance under
      standardised test conditions. At NPL, we have developed a reference test facility
      for measuring detector sensitivity to meet the needs of manufacturers, and to
      comply with the requirements of an international standard (IEC 1995) that defines
      methods of measurement of the sensitivity of fetal heart beat detectors. The test
      facility has primarily been developed for detectors operating at a transmitted
      frequency of 2 MHz and with Doppler shifts of up to 1 kHz. The detectors are
      tested by directing the ultrasound beam at a small moving target being driven at
      a constant velocity, and then monitoring the output signal from the detector,
      which will be at the Doppler shift frequency. To determine the sensitivity,
      attenuators are inserted into the beam until the output signal is reduced to 6 dB
      above the noise level. The sensitivity is calculated by adding the final signal
      level above the noise to the total insertion loss of the attenuators in the
      ultrasound path and the reflection loss of the target. A crucial aspect of this
      calculation is the knowledge of the target strengths and characteristics. This
      has already been extensively studied (Preston and Bond 1997) over the frequency
      range of interest. The NPL test facility developed for undertaking the
      sensitivity measurements is described, including an assessment of the
      uncertainties in such a measurement and solutions to problems encountered along
      the way.

PMID- 9587999
TI  - Validation of a new blood-mimicking fluid for use in Doppler flow test objects.
AB  - A blood-mimicking fluid (BMF) suitable for use in Doppler flow test objects is
      described and characterised. The BMF consists of 5 microns diameter nylon
      scattering particles suspended in a fluid base of water, glycerol, dextran and
      surfactant. The acoustical properties of various BMF preparations were measured
      under uniform flow to study the effects of particle size, particle concentration,
      surfactant concentration, flow rate and stability. The physical properties,
      (density, viscosity and particle size), and acoustical properties (velocity,
      backscatter and attenuation) of the BMF are within draft International
      Electrotechnical Commission requirements.

PMID- 9588000
TI  - High-frequency ultrasound properties of multicellular spheroids during heating.
AB  - High-frequency ultrasound monitoring is a possible method for real-time imaging
      of thermal therapy in tissues at microscopic resolution. The objective of this
      work was to measure changes in the ultrasound properties of V79 spheroids (grown
      from Chinese Hamster lung fibroblasts) exposed to heating. Spheroids are clonal
      aggregates of cells that provide a useful model for investigating the ultrasound
      properties of cells in the absence of connective tissue. Relative echo signal
      power and attenuation coefficients were measured over the frequency range 30 MHz
      to 70 MHz, from spheroids heated from 37 degrees C to 50 degrees C or 60 degrees
      C. Echo signal power from the viable rim decreased during the first 5 min by a
      factor of 1.08 before the spheroid reached 50 degrees C. For the next 25 min,
      echo signal power rose to a factor of 1.27 above the initial level, after which
      it remained relatively constant over the remainder of the 50 degrees C heating
      period. At 60 degrees C, echo signal from the viable rim remained relatively
      constant, although it appeared to have possibly decreased slightly over the
      duration of the heating period. Echo signal power from the necrotic core fell to
      a factor of 1.4 and 1.54 below the initial level at 50 degrees C and 60 degrees
      C, respectively. First-order chemical rate analysis applied to the echo signal
      power results in the viable rim at 50 degrees C revealed a rate constant for the
      5-15-min heating interval. Interpretation of the echo signal power results in
      terms of histological stains indicates that the rise in echo signal power at 50
      degrees C was due to a loss of cell cohesion, and the possible drop in echo
      signal power at 60 degrees C was due to spheroid coagulation. Attenuation
      coefficients decreased by up to 1.54 dB mm-1 over a 30-min period at 60 degrees
      C. The appearance of a real-time ultrasound image of lesion formation in cells is
      discussed.

PMID- 9588001
TI  - Standard properties of ultrasound contrast agents.
AB  - A standardization procedure for in vitro acoustic characterization of ultrasound
      contrast agents is presented. One new acoustic parameter for particular
      importance is retained: This is STAR, scattering-to-attenuation ratio, for
      quantification of the effectiveness of the contrast agent. The STAR expresses the
      ability of the contrast agent to enhance the visualization of the tissue
      containing the contrast agent and, at the same time, represents the degree of its
      absorption. So, it is desirable to produce a contrast agent with high STAR,
      having good scattering properties to improve the image visualization, and low
      attenuation to image the underlying biological structures and to avoid shadowing.
      In this study, we present methods for calculations and measurements of the STAR
      and comparison between different contrast agents.

PMID- 9588002
TI  - Glycosyl hydrolases from hyperthermophilic microorganisms.
AB  - Glycosyl hydrolases from hyperthermophiles are, thus far, the most widely studied
      enzyme class from these organisms. Not only are there many biotechnological
      opportunities for these enzymes, but the rapidly increasing amount of information
      about their genetic, biochemical and biophysical characteristics (recently
      genomic sequencing data for both P. furiosus and P. horikoshi have been published
      on the Internet) make them ideal candidates for the study of biocatalysis and
      protein thermostability at extremely high temperatures.

PMID- 9588003
TI  - Advances in hematopoietic stem cell culture.
AB  - Recent advances in our understanding of the earliest stages of hematopoietic cell
      differentiation, and how these may be manipulated under defined conditions in
      vitro, have set the stage for the development of robust bioprocess technology
      applicable to hematopoietic cells. Sensitive and specific assays now exist for
      measuring the frequency of hematopoietic stem cells with long-term in vivo
      repopulating activity from human as well as murine sources. The production of
      natural or engineered ligands through recombinant DNA and/or combinatorial
      chemistry strategies is providing new reagents for enhancing the productivity of
      hematopoietic cell cultures. Multifactorial and dose-response analyses have
      yielded new insight into the different types and concentrations of factors
      required to optimize the rate and the extent of amplification of specific
      subpopulations of primitive hematopoietic cells. In addition, the rate of
      cytokine depletion from the medium has also been found to be dependent on the
      types of cell present. The discovery of these cell-type-specific parameters
      affecting cytokine concentrations and responses has introduced a new level of
      complexity into the design of optimized hematopoietic bioprocess systems.

PMID- 9588004
TI  - Apoptosis in cell culture.
AB  - Most cells can exhibit a biochemical pathway which mediates their own destruction
      in a highly controlled and genetically defined manner. In animal cells, a
      morphologically distinct form of this 'programmed cell death' has been identified
      and extensively characterised. This phenomenon, which has been named apoptosis,
      accounts for most of the cell deaths that take place during the production of
      biopharmaceuticals from animal cell lines. In the past few years, the factors
      responsible for the induction of apoptosis in the bioreactor environment have
      been identified. Furthermore, a growing number of studies have demonstrated that
      the suppression of apoptosis by the overexpression of anti-apoptosis genes, most
      notably bcl-2, result in improved culture productivity.

PMID- 9588005
TI  - Biochemical recovery and purification of gene therapy vectors.
AB  - Rapid progress has been made with the molecular design of novel viral and non
      viral gene therapy vectors. Exploiting upstream processes of producer cell
      culture and downstream operations adapted from protein recovery, vectors have
      been accumulated in quantities and purities appropriate for the initiation of
      clinical trials. It is not clear, however, if such methodologies will be
      appropriate for efficient operation at the manufacturing scales required for
      clinically successful vectors. Technologies suited to the fractionation of
      nanoparticles may bypass practical bottlenecks experienced by current processes.
      The behaviour in such fractionation systems of natural and synthetic particles,
      which variously mimic the size, density and surface chemistry of vector products,
      could benefit the improved design of efficient manufacture for gene therapy
      vectors.

PMID- 9588009
TI  - Interstadial variation in the attachment sites of Ixodes ricinus ticks on sheep.
AB  - The spatial aggregation of ticks feeding on vertebrate hosts has been recognized
      for some time but, for hosts supporting more than one stage of the tick,
      observations of interstadial variation in the site of attachment have not
      previously been quantified. This study showed that all three parasitic stages of
      Ixodes ricinus ticks feeding on sheep attach most commonly to the hair-covered
      areas of the head and limbs while few ticks attach to the fleeced region of the
      body. However, significant differences were observed in the site of attachment of
      the three feeding stages of the tick. Larvae attached to distal limbs and rostral
      areas of the head and adult females attached to the proximal areas of the limbs
      and around the neck and ears, while nymphs attached in locations between the
      larvae and adults. The importance of the spatial aggregation of the ticks and
      interstadial variation in their distribution on the host, for the transmission of
      tick-borne pathogens and the epidemiology of the diseases they cause, is
      discussed.

PMID- 9588010
TI  - Optimal sampling and spatial distribution of Ixodes pacificus, Dermacentor
      occidentalis and Dermacentor variabilis ticks (Acari: Ixodidae).
AB  - A common method for sampling tick populations is flagging, which is a method of
      dragging a white cloth over a plant substrate for a fixed distance along a
      transect. Flagging over rough physical surfaces or using long subtransect lengths
      could lead to the underestimation of tick densities. Using estimates of the drop
      off rates of adult Ixodes pacificus in flag sampling, optimal sampling schemes
      (the length and number of subtransects) were examined using the relationships
      between the tick drop-off rates (c), the tick density and distribution patterns
      and the roughness of the sampled plant substrate. It was found that the optimal
      number of subtransects and Lmax, the longest subtransect length which did not
      significantly underestimate the tick density from c, were affected by the tick
      density, substrate roughness and tick distribution pattern. This study also
      showed that the density and distribution of I. pacificus and Dermacentor
      occidentalis varied greatly over time in the populations sampled, while the
      Dermacentor variabilis densities were low and showed no significant changes over
      time. Both I. pacificus and D. occidentalis had clumped distributions along
      trails and these clumps were aggregated. However, the clump sizes (or individual
      clump areas) changed significantly over time because of density fluctuation or
      the movement of ticks. Finally, a positive association between the number of I.
      pacificus and D. occidentalis adults was observed from 2 m subtransect flag
      collections in March 1995; no relationship was found in 1994.

PMID- 9588011
TI  - Characterization of mixed micellar pseudostationary phases in electrokinetic
      chromatography using linear solvation energy relationships.
AB  - The influence of mixed micellar systems on retention and selectivity in micellar
      electrokinetic chromatography is examined using linear solvation energy
      relationships (LSER). Systems that were investigated include mixed bile salts
      [sodium deoxycholate (SDC) and sodium cholate (SC)] and mixed sodium dodecyl
      sulfate (SDS)-bile salt systems (e.g., SDS-SC and SDS-SDC). The retention
      behavior in individual and mixed micellar systems is primarily determined by size
      and hydrogen bond acceptor strengths of solutes. Through a comparative study of
      the LSER coefficients in the individual and mixed micellar systems, it was
      concluded that hydrogen bonding interactions have a significant effect on
      selectivity of these pseudostationary phases in electrokinetic chromatography.
      The interactive properties of the mixed micelles are different from the
      constituent individual micelles, however, the overall characteristics are closer
      to one of the bile salt micelles in the mixture even at the equimolar
      compositions.

PMID- 9588013
TI  - Micellar electrokinetic chromatography of scopolamine-related anticholinergics.
AB  - A simple micellar electrokinetic chromatography (MEKC) method is described for
      the separation of scopolamine N-oxide hydrobromide (SO), scopolamine hydrobromide
      (SH), scopolamine N-methylbromide (SM) and scopolamine N-butylbromide (SB), and
      for the quantitation of SH, SM and SB (using SO as an internal standard). The
      analysis of these drugs was performed in a phosphate buffer (30 mM; pH 7.00) with
      sodium dodecyl sulfate (SDS) (30 mM) as an anionic surfactant. Several parameters
      affecting the separation of the drugs were studied, including the concentrations
      of the buffer and SDS. The stability of the drugs in the phosphate buffer (pH
      7.00) was also examined. Partial application of the method to the determination
      of scopolamine N-butylbromide in tablets proved to be feasible.

PMID- 9588012
TI  - Migration behavior and separation of tetracycline antibiotics by micellar
      electrokinetic chromatography.
AB  - The migration behavior and separation of six tetracyclines (TCs) were
      investigated by micellar electrokinetic chromatography (MEKC) in the pH range 5.0
      9.0 using ammonium acetate buffer with the addition of sodium dodecyl sulfate
      (SDS). Mixed SDS-Brij 35, sodium cholate (SC) and tetradecyltrimethylammonium
      bromide (TTAB) were also used as surfactants. The influences of surfactant
      concentration and buffer pH on the separation of TCs were examined and the
      separations of TCs were optimized. Complete separation of six TCs was achieved
      within 8 min with 15 mM ammonium acetate buffer containing 20 mM SDS, with or
      without the addition of Brij 35 (0.135%, w/v), at pH 6.5 using a fused-silica
      capillary (42 cm x 75 microns I.D.) at 15 kV. In general, good linear
      correlations of the logarithm of migration factor (log k') versus the logarithm
      of octanol-water partition coefficient (log P(ow)) in these micellar systems,
      except for the TTAB-MEKC system, were obtained. The results indicate that the
      migration of TCs in MEKC is mainly based on hydrophobic interactions. However,
      hydrogen bonding interactions also play a significant role in influencing the
      chemical selectivity of TCs. In addition, the micelle-water partition
      coefficients (Pmw) of TCs, which are pH-dependent in the SDS-MEKC micellar
      system, are reported.

PMID- 9588014
TI  - Determination of naproxen in liver and kidney tissues by electrokinetic capillary
      chromatography with laser-induced fluorescence detection.
AB  - Pharmacotherapy through the targeting of drugs is a promising new approach that
      requires adequate analytical methods capable of monitoring the free drug, the
      drug carrier and metabolites in body fluids and organs. A micellar electrokinetic
      capillary chromatography (MECC) based assay for analysis of naproxen (NAP) in
      extracts of hydrolyzed liver and kidney tissue homogenates using salicylate as
      internal standard and solute detection by laser-induced fluorescence is reported.
      The assay described uses 100 microliters of hydrolyzed tissue homogenate and has
      a detection limit of 0.07 microgram/ml. It is shown to be selective, reproducible
      (at a NAP level of 0.25 microgram/ml, intra-day and inter-day R.S.D. values are
      3.73% and 6.39%, respectively), simple and economical (operates with inexpensive
      separation columns and small amounts of chemicals). It has been successfully
      applied to the assessment of the total NAP content within liver and kidney
      tissues of male Sprague Dawley rats that have been treated with NAP conjugated to
      human serum albumin (the drug targeting carrier) and free NAP. Compared to
      previously applied techniques, including high-performance liquid chromatography,
      MECC offers the advantage of having lower running costs and lower consumption of
      organic solvents.

PMID- 9588015
TI  - Capillary zone electrophoretic determination of some drugs against Alzheimer's
      disease.
AB  - A new capillary zone electrophoresis (CZE) method for the determination of
      tacrine (THA), 7-methoxytacrine (7-MTHA) and their basic metabolites (THAm, 7
      MTHAm) in pharmaceutical and biological samples (urine and serum) was developed.
      Separation of all compounds by CZE was carried out using a 46.6 cm untreated
      fused-silica capillary applying 20 kV separation voltage using 50 mM phosphate
      buffer of pH 2.8 for THA and THAm and of pH 7.8 for 7-MTHA and 7-MTHAm as
      background electrolyte (BGE). Detection was carried out at 240 nm (THA and THAm)
      and 248 nm (7-MTHA and 7-MTHAm). THA and THAm were separated in less than 4 min
      while 7-MTHA and 7-MTHAm were separated in less than 7 min. The detection limits
      (SIN = 3) obtained were 3 ppb for THA and 4 ppb for 7-MTHA in aqueous solutions;
      50 ppb for THA and 47 ppb for 7-MTHA for the determination in urine (diluted
      1:10); 52 ppb for THA and 56 ppb for 7-MTHA, in deproteinized serum samples. The
      methods are suitable for therapeutic drug monitoring of the drugs.

PMID- 9588016
TI  - Capillary isoelectric focusing of the scrapie prion protein.
AB  - Prion diseases or transmissible spongiform encephalopathies belong to a group of
      neurodegenerative diseases that infect both animals and humans. These diseases
      are associated with an accumulation of fibrils in the brains of infected
      individuals. These fibrils are composed of an abnormal isoform of a host-encoded
      glycoprotein that is characterized by its insolubility and partial resistance to
      proteases. Another characteristic of the scrapie prion protein (PrPsc) is the
      wide range of isoelectric points (pI values) that have been observed on
      conventional isoelectrofocusing gels. In this study, we explored the use of
      capillary isoelectric focusing (cIEF) to characterize the pI values for PrPsc
      isolated from sheep and hamster brain. We used a Beckman 5500 P/ACE using UV
      detection at 280 nm. A cIEF 3-10 Kit from Beckman Instruments was used to perform
      the analysis. The PrPsc was solubilized in 0.01 M Tris-HCl, pH 8.00 containing 2
      mM EDTA. 5% SDS and 10% hexafluoroisopropanol at 100 degrees C for 10 min. The
      solubilized PrPsc was placed over a high-performance hydrophilic interaction
      column. After elution, the peaks were concentrated and assayed for
      immunoreactivity with specific antisera. The peaks that contained
      immunoreactivity were then placed on the cIEF capillary. The samples containing
      PrPsc were solubilized in 1% n-octylglucoside before isoelectric focusing. The
      scrapie infected sheep sample had peaks with pI values ranging from 5.2 to 3.00
      with a major peak at 3.09. The normal sheep brain had pI values that were higher.
      The hamster adapted scrapie strain had peaks with pI values ranging from 6.47 to
      3.8. These pI values were slightly higher than those obtained for the sheep
      samples. The use of cIEF to determine the pI values of PrPsc led to the
      identification of a major species of PrPsc from sheep with a very acidic pI.

PMID- 9588018
TI  - Analysis of Puerariae radix and its medicinal preparations by capillary
      electrophoresis.
AB  - This study presents a high-performance capillary electrophoresis (CE) method to
      analyze five constituents of Puerariae radix, an important crude herb used in
      Chinese medicine. Puerarin, daidzin, daidzein, genistein and biochanin A are the
      bioactive constituents of Puerariae radix. Herein, those analytes were
      successfully separated within 6 min using a pH 10.1 borax-NaOH buffer. The
      effects of pH value and concentration of the running buffer on the separation of
      the five analytes were also examined. The relative standard deviations of the
      analytes' migration times were less than 0.38% under the optimized separation
      conditions. Notably, the correlation coefficients of the analytes' linear
      calibration graphs exceeded 0.998. Moreover, the amounts of the five constituents
      in three different Puerariae radix samples were determined by the CE method with
      a relatively simple extraction procedure.

PMID- 9588017
TI  - Sodium dodecyl sulfate-capillary gel electrophoretic analysis of molecular mass
      microheterogeneity of beta-trace protein in cerebrospinal fluid from patients
      with central nervous system diseases.
AB  - Molecular mass (M(r)) microheterogeneity of beta-trace protein (beta TP) in
      cerebrospinal fluid (CSF) from patients with various neurological disorders was
      analyzed by sodium dodecyl sulfate capillary gel electrophoresis. Under the
      conditions employed, beta TP with a M(r) distribution of 23,000-30,000 was
      roughly separated into two subfractions containing the major peaks with M(r) of
      26,000 and 28,500, respectively. The peak area ratios of the two subfractions of
      the electropherograms varied among the samples examined, and elevation in the
      total beta TP level in the CSF from patients with organic diseases in the central
      nervous system (CNS) was often accompanied by changes in the ratios of the
      subfractions. The quantitative changes in the subfraction level in CSF beta TP
      are considered to reflect the pathological alterations in the CNS.

PMID- 9588019
TI  - Determination of vitamins in food based on supercritical fluid extraction prior
      to micellar electrokinetic capillary chromatographic analyses of individual
      vitamins.
AB  - The separation of 14 water-soluble vitamins and vitamin cofactors was
      investigated by micellar electrokinetic capillary chromatography and diode array
      detection using sodium cholate as the micellar phase. The method was optimised
      with respect to the effect of buffer composition, capillary temperature and
      applied voltage resulting in separation of all compounds in about 25 min. With
      the current method it is possible to predict the eluting order of the individual
      compounds from their net charges of each compound because of a low ion pairing
      between solutes and micelles. The linearities within concentration ranges of up
      to two-orders of magnitudes were good with correlation coefficients from 0.971 to
      0.997. The separation efficiency was satisfactory with a good resolution ranging
      from 2 to 45 and a theoretical number of plates varying from 200,000 to 480,000.
      The repeatability of the developed method showed relative standard deviations on
      migration time in the range from 0.5% to 1.2% (n = 15) and for normalised peak
      areas, relative standard deviations were approximately 6%.

PMID- 9588020
TI  - The fracture-flip technique reveals new structural features of the Escherichia
      coli cell wall.
AB  - With few exceptions, all bacteria possess a wall which protects them and controls
      their communication with the environment. In Gram-negative bacteria the cell wall
      exhibits a complex and unique multilayered organization. We have applied a
      modification of the freeze-fracture technique known as 'fracture-flip' to
      visualize the real surfaces of the different wall layers in a Gram-negative
      bacterium, Escherichia coli. In combination with treatments to weaken the
      interlayer connections, this technique has provided new insights into the
      structure of the bacterial wall. Large areas of an intermediate layer (most
      probably the peptidoglycan-containing matrix) have been visualized for the first
      time between the plasma membrane and the outer membrane of the wall. Extensive
      regions corresponding to the cytoplasmic face of the plasma membrane have also
      been obtained. These images provide new three-dimensional views of the bacterial
      cell wall and provide the structural framework for the analysis of the molecular
      relationships between the different cell wall components.

PMID- 9588021
TI  - Ultrastructure of the frog retina after high-pressure freezing and freeze
      substitution.
AB  - In many types of tissue, high-pressure freezing (HPF), followed by freeze
      substitution, can produce excellent ultrastructural preservation at depths over
      10 times that obtained by other cryofixation techniques. However, in the case of
      neural tissue, the benefits of HPF have not been realized. In the present study,
      isolated frog (Rana pipiens) retina was sliced at a thickness of 150 or 350
      microns, rapidly frozen in a Balzers HPM 010 high-pressure freezer, and freeze
      substituted with 1% OsO4 and 0.1% tannic acid in acetone. Specially designed HPF
      chambers and specific freezing media (35% high-MW dextran for 150-micron slices
      or 15% low-MW dextran for 350-micron slices) were required for adequate freezing.
      The quality of preservation after HPF was excellent throughout the retina in both
      the 150- and 350-micron slices, compared with chemically fixed slices.
      Specifically, HPF resulted in better preserved cellular, mitochondrial and
      nuclear membranes in all retinal layers. This is the first study to successfully
      cryofix all of the layers of the retina. The increased depths of adequate
      freezing achieved by HPF should facilitate various ultrastructural studies of
      retina, as well as of other CNS tissues, where preservation approaching that of
      the 'native' state is required.

PMID- 9588022
TI  - Electron microscopy of frozen biological objects: a study using cryosectioning
      and cryosubstitution.
AB  - Freezing of bulk biological objects was investigated by X-ray cryodiffraction.
      Freezing at atmospheric pressure of most microscopic biological samples gives
      rise to large hexagonal crystals and leads to poor structural preservation of
      these specimens. High-pressure freezing induces the formation of different ices
      (hexagonal, cubic and a high-pressure form) consisting of crystals having sizes
      smaller than those formed at atmospheric pressure. With both freezing methods, a
      cryoprotectant has to be added to the biological object to avoid the formation of
      ice crystals. However, special cases can be encountered: some biological objects
      contain large amounts of natural cryoprotectant or have a low water content. In
      these cases, vitrification can be achieved, especially using high-pressure
      freezing. Cryo-sectioning can be performed on vitrified samples, and the sections
      studied by electron cryomicroscopy. Images and electron diffraction patterns
      having a resolution better than 2 and 0.2 nm, respectively, can be obtained with
      such sections. Because samples containing crystalline ices cannot be
      cryosectioned, their structure has to be studied using cryosubstitution and resin
      embedding. We show that bacteria, yeast, and ciliate and marine worm elytrum have
      cellular compartments with an organization that has not been described by
      classical techniques relying on chemical fixation of the tissues. A high-pressure
      artefact affecting the Paramecium trichocysts is described. Such artefacts are
      not general; for example, we show that 70% of high-pressure frozen yeast cells
      survive successive high-pressure freezing and thawing steps.

PMID- 9588023
TI  - Analysis of cycles of dormancy and growth in pea axillary buds based on mRNA
      accumulation patterns of cell cycle-related genes.
AB  - Axillary buds of pea (Pisum sativum L. cv. Alaska) do not grow on intact plants.
      Dormant axillary buds can be stimulated to grow rapidly after decapitation. Here,
      we isolated cDNAs of PCNA, cyclinB, cyclinD, and cdc2 from pea. The mRNA
      expression levels of these genes were very low in dormant axillary buds, whereas
      they remarkably increased after decapitation. Based on the mRNA accumulation
      patterns of these genes, we found that most cells in dormant axillary buds are
      arrested at the G1 phase in the cell cycle. There are four buds at the second
      node on pea seedlings. After decapitation, mRNAs became abundant in the large and
      small buds and were kept during the following 3 d. After 4 d, mRNAs were still
      present in the large bud, but not in the small bud. However, after removal of the
      large bud, the mRNA levels started to increase again in the small bud. These mRNA
      accumulation patterns were the same as those after the first decapitation. These
      results suggested that most cells in axillary buds at the second node are
      arrested at the G1 phase again and have the capacity to undergo multiple cycles
      of dormancy and growth. Moreover, in situ hybridization analyses demonstrated
      that PCNA mRNA increased in all parts of the axillary buds after decapitation.

PMID- 9588024
TI  - Properties of the respiratory NAD(P)H dehydrogenase isolated from the
      cyanobacterium Synechocystis PCC6803.
AB  - Activity staining with NADPH-nitroblue tetrazolium after native-PAGE of membrane
      proteins of Synechocystis PCC6803, solubilized with 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), revealed four
      NAD(P)H dehydrogenase (NDH) activities; an NDH complex of the respiratory chain,
      a ferredoxin NADP+ reductase (FNR), a drgA product which oxidized both NADH and
      NADPH, and an uncharacterized NADH-specific enzyme. The NDH complex was purified
      with anion exchange and gel filtration chromatographies. The purified complex had
      a molecular mass of 376 kDa and was composed of 9 subunits. Western analysis
      showed that the complex contained the NDH-H subunit, but not NDH-A or B. The
      enzyme reduced ferricyanide much faster than plastoquinone and used NADPH as its
      preferred electron donor rather than NADH. The enzymatic activity was inhibited
      by diphenyleneiodonium chloride and salicylhydroxamic acid, but not by rotenone,
      p-chloromercuribenzoate, N-ethylmaleimide, flavon, dicumarol, or antimycin A.
      These results suggest that the purified complex is a hydrophilic subcomplex which
      contains an NADPH binding site and flavin, and is dissociated from a hydrophobic
      subcomplex, which contains quinone binding site.

PMID- 9588025
TI  - Cloning and expression of the soybean chlH gene encoding a subunit of Mg
      chelatase and localization of the Mg2+ concentration-dependent ChlH protein
      within the chloroplast.
AB  - From the soybean cDNA library, we isolated and analyzed the chlH gene encoding a
      subunit of Mg-chelatase. The subunit was a polypeptide of 1,383 amino acids with
      a molecular mass of 153,491 Da, which shared 90% identity with the olive gene
      from Antirrhinum majus. The regulation of the expression of chlH was investigated
      in photomix-otrophic soybean suspension cells (SB-P). The expression was light
      inducible, and the induction was more rapid than those of chlI and cab2.
      Furthermore, the levels of the transcripts and products of chlH appeared to be
      regulated by a circadian oscillation. The subchloroplastic localization of ChlH
      was investigated by immunoblot analyses with antiserum against recombinant ChlH.
      Depending on the concentration of Mg2+ in the lysis buffer, the localization of
      ChlH protein migrated between the stroma and the envelope membrane; ChlH was
      localized on the envelope membrane, a major site of chlorophyll biosynthesis,
      when the Mg2+ concentration of the lysis buffer was high (above 5 mM). These
      results indicated that the activity of Mg-chelatase was regulated by modulation
      of the expression and subchloroplastic localization of ChlH protein.

PMID- 9588027
TI  - cDNA cloning, gene expression and secretion of chitinase in winged bean.
AB  - cDNA for an acidic class III chitinase (ChitW1) was isolated from winged bean
      cells. The chitinase was abundantly secreted at later stages of cell culture,
      when levels of ChitW1 mRNA were also high. The gene was strongly expressed in
      roots, but a class I chitinase was strongly expressed in leaves.

PMID- 9588026
TI  - The modular structure and function of the wheat H1 promoter with S phase-specific
      activity.
AB  - Two histone H1 genes, TH315 and TH325, were isolated from a wheat genomic
      library. Nucleotide sequence analysis and comparison with other histone gene
      promoters revealed that the promoters of both genes contain many characteristic
      motifs conserved among plant histone H1 genes. They are 6 novel short stretches,
      named CS1 to CS6, and already documented elements or their relatives such as Oct,
      Oct-like (OLS), Nona-like (NonaLS), CCAAT box, and TATA box. Transient expression
      experiments with the TH315 promoter/GUS chimeric gene and its mutagenized
      derivatives showed that two Oct motifs, OLS, and CCAAT box are positive cis
      acting elements. NonaLS and CS4 were suggested to be positive cis-acting elements
      and CS5 and CS6 to be negative elements. An Oct motif and CCAAT box constitutes a
      type III element and the 202-bp sequence containing these elements from -128 to
      +74 of the TH315 gene was shown to be sufficient to confer S phase-specific
      expression. The type III element is found in all plant histone H1 and H2B genes,
      suggesting that it is a subtype-specific element. Most plant histone genes have
      one of the type I, II, and III elements. We propose to classify the plant histone
      genes into three classes, based on the context of Oct in the promoters.

PMID- 9588028
TI  - Dark-induced accumulation of mRNA for a homolog of translationally controlled
      tumor protein (TCTP) in Pharbitis.
AB  - A cDNA encoding a homolog of human translationally controlled tumor protein
      (TCTP) was isolated from cotyledons of the short-day plant Pharbitis mil cv.
      Violet. The level of the corresponding mRNA increased gradually during darkness.
      This increase was inhibited by end-of-day exposure to far-red light.

PMID- 9588029
TI  - InJection adaptable fine ionization source ('JaFIS') for continuous flow nano
      electrospray.
AB  - Nanoelectrospray ('nanoES') tandem mass spectrometry of complex peptide mixtures
      has become a certified, mostly reliable technique for the identification of
      proteins. The typical low flow rates of nanoES, the extended analysis times for
      small samples, high ion transmission and its overall ease-of-use provide
      important practical advantages for polypeptide covalent microanalysis. We have
      constructed a modified nanoES ion source that is highly durable and user
      friendly, and potentially allows for full auto-sampling operation. The inJection
      adaptable Fine Ionization Source ('JaFIS') can be operated at flow rates of 10
      100 nL per minute and with sensitivities in the 25 femtomoles peptide per
      microliter range. The ion spray needles usually last for days, allowing for
      standards and multiple samples to be analyzed consecutively under similar
      conditions. In this configuration, quality controlled needles can also be saved
      and reused, providing for more consistent and reproducible day-to-day operating
      conditions, JaFIS-ES also permits sample recovery should any failure occur during
      analysis.

PMID- 9588030
TI  - Analysis of the degradation mechanisms of MHC class I-presented tumor antigenic
      peptides by high performance liquid chromatography/electrospray ionization mass
      spectrometry: application to the design of peptidase-resistant analogs.
AB  - Peptide vaccines based on the use of MHC class I restricted epitopes are
      currently assayed for anti-tumor and anti-viral immunotherapy. With the aim of
      designing minimally modified, peptidase-resistant analogs, we developed a
      rational approach based on a detailed understanding of the degradation mechanism
      of peptides in serum. Degradation of murine tumor antigen P198 and human tumor
      antigen MAGE-3.A1 was followed by on line high performance liquid
      chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS). This
      method provided high precision and sensitivity for rapid and direct analysis of
      degradation fragments in a complex mixture and, very importantly, precise
      identification of transient degradation fragments present at low concentrations.
      The design of structurally modified analogs, and the analysis of their
      degradation by on-line HPLC/ESI-MS, allowed us to to demonstrate the efficiency
      of local modifications in the protection of a given peptide bond towards a
      specific peptidase activity.

PMID- 9588032
TI  - [French cytopathology at the dawn of the 3rd millennium].

PMID- 9588031
TI  - Is canine hepatocerebellar degeneration syndrome an animal model for carbohydrate
      deficient glycoprotein syndrome in humans? An example of sequencing glycoprotein
      glycans with mass spectrometry.
AB  - The clinical symptoms and morphologic features of canine hepatocerebellar
      degeneration syndrome (CHD) bear striking resemblance to those of human
      carbohydrate-deficient glycoprotein syndrome (CDGS). The characteristic
      biochemical and molecular features of human CDGS lie in the truncated
      carbohydrate side chains of serum transferrin and numerous other glycoproteins of
      affected persons. Therefore, to explore the biochemical similarities between CHD
      and CDGS, we compared the structures of the carbohydrate side chains of canine
      serum transferrin isolated from a normal and a CHD-affected dog. Because of the
      very small quantity of serum transferrin available from the CHD-affected dog, we
      used analytical procedures that minimize sample consumption. In this scheme, we
      used microbore liquid chromatography interfaced to electrospray tandem mass
      spectrometry to identify and purify the glycopeptides from the tryptic digest of
      canine serum transferrin. This was followed by a series of exoglycosidase
      digestions coupled with mass spectrometric detection to sequence the carbohydrate
      side chains of the glycopeptides. With these procedures we completely
      characterized the carbohydrate chains attached to serum transferrin isolated from
      both a normal and a CHD-affected dog. However, we found no discernible
      differences in glycosylation of the carbohydrate side chains of serum transferrin
      from these two animals, suggesting that the biochemical defect in puppies with
      CHD differs from that in children with CDGS.

PMID- 9588033
TI  - [Societe Francaise de Cytologie Clinique training course. Why?].

PMID- 9588034
TI  - [Diagnostic pitfalls in bronchopulmonary tumors].
AB  - Bronchopulmonary cytopathology is an already old diagnostic method for lung
      tumours. Its has been the subject of renewed interest following the development
      of techniques which complete brushing and aspiration by bronchial fibroscopy such
      as bronchoalveolar lavage, transthoracic pulmonary fine needle biopsy and
      transbronchial and transtracheal needle biopsy. Diagnostic difficulties depend on
      both the tumour type and the biopsy technique. Keratinizing squamous cell
      carcinoma is difficult to distinguish from dyskeratotic cells on aspiration
      cytology and inflammatory and granulomatous necrosis on transparietal lung
      biopsy. Non-keratinizing squamous cell carcinoma must not be confused with
      atypical metaplastic cells on bronchial brushing. Bronchioloalveolar carcinoma
      must be distinguished from reactivated bronchioloalveolar cells on bronchial
      aspiration; pulmonary adenocarcinoma must not be confused with atypical
      bronchiolar cell hyperplasia on transparietal lung biopsy. The naked nuclei of
      small cell carcinoma on bronchial brushing and transparietal lung biopsy differ
      from those of malignant small cell lymphoma and carcinoid. Bronchopulmonary
      cytopathology is able to diagnose the main types of bronchial and pulmonary
      tumours with a good sensitivity. The overall sensitivity of detection is
      excellent, ranging between 90 and 92% depending on the method. The false-positive
      rate is less than 0.5% for experienced cytopathologists.

PMID- 9588035
TI  - [Bronchoalveolar lavage].
AB  - Bronchoalveolar lavage (BAL) has become one of the usefull biological
      explorations in pneumology. It has prooven to be efficient for the diagnosis of
      chronic as well as acute interstitial pneumoniae.

PMID- 9588036
TI  - [Morphology of lesions of the uterine cervix and human papillomaviruses].

PMID- 9588037
TI  - [Cytology of malignant endometrial tumors].
AB  - Endometrial cytology is made by direct endometrial sampling. It allows the
      appreciation of the hormonal status and the diagnosis of inflammatory and/or
      tumoral pathology. Evidence has been presented that the rate of endometrial
      cancer is on the increase. Thus, detection and diagnosis have acquired a new
      significance, where endometrial cytology takes a particular place. Cytologic
      features of adenocarcinomas in their different kinds are presented. Furthermore,
      cytologic aspects of uterine sarcomas are outlined, including leiomyosarcomas
      whose diagnosis can be made by the mean of endometrial cytology.

PMID- 9588038
TI  - [Cytopathology of the breast].
AB  - Cytologic diagnosis is a useful tool for diagnosis of breast lesions. It is also
      useful in the follow-up of non operated lesions and overall in the follow-up of
      breast carcinomas. Technical improvements (immunocytochemistry, flowcytometry,
      image analysis) are applicable to cytologic material and permits to obtain
      prognostic factors in breast cancer. Quality of samples, smears, stainings and of
      cytologic interpretation are prerequisite for the reliability of this method.

PMID- 9588039
TI  - [Thyroid cytopathology].
AB  - Rigorous techniques of fine-needle sampling, smearing and staining are mandatory
      for optimizing the value of thyroid cytopathology. As on frozen sections,
      follicular lesions should be interpreted with caution.

PMID- 9588040
TI  - [Guided fine needle puncture in the diagnosis of pancreatic disorders].
AB  - Fine-needle aspiration (FNA) of pancreatic disorders with ultrasound or computed
      tomographic, and recently echo-endocopic guidance has become commonplace to
      diagnose the nature of a pancreatic lesion. It is specially usefull in diagnosing
      solid neoplasms. Most often, FNA is performed to confirm a diagnosis of ductal
      adenocarcinoma. The aspirate shows cellular clusters with high nuclear-to
      cytoplasmic ratio, overlapping nuclei and prominant macronucleoli. The cytologic
      features that permit a diagnosis of neuroendocrin neoplasm are loose cellular
      aggregates with round nuclei, evently dispersed nuclear chromatin, a moderate
      amount of amphophilic cytoplasm and rosette formation. Immunocytochemistry can
      provide additional confirmatory information. Difficulties are encountered in
      diagnosing cystic neoplasms. The major cytologic differences between serous and
      mucinous tumors are the absence of mucin and presence of low cuboidal glycogen
      containing cells in the microcystic adenoma vs the presence of goblet cells in
      the mucinous tumors. Except for the presence of necrotic debris, and in the
      absence of obvious malignant cytologic features, it is impossible to predict the
      behaviour of mucinous neoplasms. The lower accuracy for cystic neoplasm can be
      attributed to predominantly bloody specimens and limited cellularity. These
      problems illustrate the importance of knowing the clinical and radiological
      features of pancreatic cystic neoplasms.

PMID- 9588041
TI  - [Cytology of renal and adrenal gland masses in adults].
AB  - Fine needle aspiration cytology (FNA) of renal masses and adrenal glands don't
      really differ from FNA of other sites. Nevertheless, only few series have been
      published on this subject, and surgery remains the most conventional attitude
      after the clinical and radiological diagnosis of a mass. The aim of this "lesson"
      is to demonstrate that this technique is accurate for kidneys and adrenal glands
      too.

PMID- 9588042
TI  - [Cytopathology of cerebrospinal fluid].
AB  - Cytological examination of cerebrospinal fluid provides extremely useful
      informations and contributes to the diagnosis of infection, inflammation or
      neoplasia. Reliable technical procedures and knowledge of the clinical data are
      mandatory. Cytological features are described. Current cytodiagnostic dilemmas
      and pittfalls are reviewed including interpretation of cell clusters, lymphocytic
      cell population and cellular modifications due to sampling from
      ventriculoperitoneal shunts.

PMID- 9588043
TI  - [Answers to the self-evaluation test. Societe Francaise de Cytopathologie
      Clinique. Cytopathology course, Paris, January 20-25 1997].

PMID- 9588044
TI  - [Eulogy of Jean-Claude Rudler (1906-1982)].

PMID- 9588045
TI  - [Treatment of common bile duct lithiasis: first-line endoscopic sphincterotomy
      and celioscopic cholecystectomy].
AB  - The aim of this study was to assess retrograd cholangiogram findings and first
      line endoscopic sphincterotomy followed by laparoscopic cholecystectomy for the
      treatment of main bile duct lithiasis. Clinical, biological and echographic
      criteria predictive of main bile duct lithiasis were observed in 125 patients (32
      men, 93 women, mean age 44.2 years) who underwent retrograde cholangiography.
      Results suggested lithiasis of the main bile duct in 105 case (87.5%) and were
      confirmed at endoscopic sphincterotomy in 99. There were no deaths; four
      complications occurred (3 moderate cases of pancreatitis, 1 cholecystitis).
      Conversion was required in 11.6%, usually because of difficulties in dissecting.
      No residual lithiasis was observed. Mean duration of hospitalization was 11.4
      days. This sequential treatment scheme for main bile duct lithiasis appears to be
      effective, minimally invasive and safe.

PMID- 9588046
TI  - [37 so-called biliary cysts of the liver in adults].
AB  - Clinical manifestations, clinical course and therapeutic schemes were studied in
      37 patients with a surgical indication for biliary cysts of the liver observed in
      a surgery unit over 25 years. Cyst size varied from 2 to 30 cm and was greater
      than 10 cm in 12 cases. Yellowish-clear contents were observed in 23 cases and
      purulent or hemorrhagic contents in 3 each. Twenty-three patients were
      asymptomatic, 14 had pain and/or complications (hemorrhage 3, infection 3,
      compression 3, rupture 1). Therapy was abstention in 7 cases, puncture in 5,
      resection of the protruding dome in 17, complete exeresis in 5, and hepatectomy
      in 3. There were no deaths and morbidity reached 7%. Biliary cysts of the liver
      can be discovered fortuitously at surgery or imagery or in patients with
      abdominal pain, an abdominal mass or complications including compression,
      intraperitoneal rupture, intracystic hemorrhage, hemobilia, acute infection,
      torsion, cancerization. Diagnosis requires sonography and computed tomography.
      Therapeutic indications are: abstention for small asymptomatic cysts. For
      voluminous cysts, with complications or confirmed during a supramesocolic
      operation, the risk of recurrence or aggravation of the complications excludes
      puncture or injection of a sclerosing agent. Wide resection of the protruding
      part of the cyst with histology resection can be performed although prospective
      assessment is needed. Cystectomy is not indicated if there is a diagnostic doubt.
      Hepatectomy is an exceptional indication retained for patients with uncontrolable
      hemorrhage, intra-cystic tumors or voluminous cysts destroying the lobe.

PMID- 9588047
TI  - [Reflections on recent ruptures of the diaphragm. Apropos of 45 cases].
AB  - Trauma-induced ruptures of the diaphragm are very exceptional but are regularly
      encountered in trauma surgery units. Closed ruptures occur in 60 to 80% of
      diaphragm lesions in European series, 9 times out of 10 after traffic accidents.
      Large American trauma centers however, have had more experience with stab of
      firearm wounds. The diagnosis raises many problems and requires further
      exploration after the standard chest x-ray. We discuss the different explorations
      which can be contributive in both emergency and non-emergency situations. The
      most appropriate therapeutic approach is also discussed. Should thoracotomy or
      laparotomy be used? What precautions are required prior to surgery? Can
      laparoscopy be useful?

PMID- 9588048
TI  - [Reevaluation of surgical treatment of cancers of the anus. Therapeutic proposals
      based on an experience with 33 patients].
AB  - Radiotherapy remains the basic treatment of anal cancer especially for epidermoid
      carcinomas. Tumorectomy and rectal amputation still have indications in the many
      others histological types and also in aguamous cell carcinomas (> T2) which
      cannot be totally healed by radiotherapy or after recurrences.

PMID- 9588049
TI  - [Carotid revascularizations by venous grafting: long-term results].
AB  - Carotid artery reconstruction (CAR) may be achieved through a variety of
      techniques. The method of choice is based upon the patient's symptoms, the
      diffusion of the atheromatous lesion in the internal carotid artery and the
      experience of the surgical team that usually deals with these patients. Between
      January 1987 and May 1995, we performed 185 CAR using saphenous vein graft. The
      indication for surgery was atherosclerotic occlusive desease in all patients,
      sixty-two per cent of whom were asymptomatic. In the early postoperative period
      one patient died of aspiration, two patients suffered a stroke (one major and one
      minor) and five patients had a transcient ischemic attack due to carotid clamping
      intolerance. Two late restenosis and two graft occlusions occurred. The
      cumulative operative morbidity and mortality rate was 1.6%. This series
      demonstrates than venous grafting for carotid reconstruction yields satisfactory
      short- and long-term results and is a valuable alternative to endarteriectomy.
      Follow-up by Duplex-scan revealed no evidence of morphological degradation of the
      vein grafts.

PMID- 9588050
TI  - [Surgical treatment of genito-urinary prolapse by abdominal approach with
      promotofixation and setting of an anterior subvesical prosthesis combined with
      retropubic colpopexia: anatomical and functional results in 104 patients].
AB  - A homogeneous series of 104 patients with genito-urinary prolapse or urinary
      incontinence is reported. Surgical treatment combined promotofixation with (n =
      45) or without (n = 59) subtotal hysterectomy, retropubic colpopexia and in
      certain cases posterior colpoperineorraphia with myorraphia of the levator ani (n
      = 28). Anatomic results were excellent for bladder and uterine ptosis. Moderate
      results were obtained for rectoceles and procedures involving the posterior
      perineum. A rectovaginal prosthesis or complete repair of the rectovaginal wall
      appeared to be required to improve results for rectoceles. Urine function was
      good for urinary incontinence: 91% success. Results depended on the pressure of
      the uretral closure. A complete urodynamic work-up is required prior to surgery
      in case of sphincter failure. Poor results were also related to excessive
      posterior traction which can open the cervico-uretral angle. Treatment of genito
      urinary prolapse with promotofixation in combination with retropubic colpopexia
      is a reliable reproducible technique which gives excellent long-term results if
      excessive promontory traction is avoided and if, in certain cases, the
      rectovaginal wall is repaired or a prosthesis implanted when maximum uretral
      closure pressure is weak.

PMID- 9588051
TI  - [Rectus abdominis myocutaneous flaps].
AB  - The free transverse rectus abdominis myocutaneous (TRAM) flap is vascularized by
      the inferior epigastric pedicle. There are many techniques according to the
      indication. We describe the technique for breast reconstruction after mastectomy
      for cancer. The rectus muscle is taken between the umbilicus and the arcuate
      line. The skin paddle, was taken transversely like an abdominoplasty. The
      incision extends from 1 cm above the umbilicus to include the perforators around
      it. The mean length of the vascular epigastric pedicle is 6 cm. This study was
      performed from one hundred dissections.

PMID- 9588052
TI  - [Breast reconstruction using free rectus abdominis myocutaneous flap].
AB  - More than 50% of patients who have breast cancer do not need a mastectomy. Since
      1976, reconstruction of the breast is suitable. From 1976 to 1995, we have
      performed 220 breast reconstructions with a pediculed latissimus dorsi and 510
      reconstructions with a pediculed transverse rectus abdominis myocutaneous flap
      (TRAM). So, in all, 1100 immediate breast reconstruction with either a prosthesis
      or a pediculed flap were performed. The specialised teams aim is to use the TRAM
      free transplant for immediate breast reconstruction. Between 1990 to 1995 we have
      performed 5 free TRAM for breast reconstruction for cancer and 6 TURBOTRAM. It is
      important for the woman to have an abdominal adiposity, to be able to give an
      excellent breast. Four out of five of the free TRAM reconstructions were
      successful and one give partial necrosis (4 x 4 cm). All the 6 TURBOTRAM
      operations were uneventful. There are many advantages with this technique: the
      free TRAM allows a large resection of the thoracic skin and gives a natural form
      to the breast, without any prosthesis. The taking of the free TRAM gives only few
      abdominal hernia and realize an abdominoplasty. Our aim is to perform immediate
      breast reconstruction with free TRAM flap.

PMID- 9588053
TI  - [Problems of reoperation after prosthetic repair of groin hernia].
AB  - The easy performance and the efficiency of these repairs should make the surgeon
      attentive to some related drawbacks, which can scarcely appear when reoperating
      on the bladder or the prostate, also on the iliac vessels. The encountered
      difficulties are related to the scar sclerosis much or less extensive and/or
      effective, invading the Retzius and/or the Bogros' spaces. The authors report
      their intraoperative and anatomical findings. They propose the following
      solutions: (1) when the cleavage of the Retzius' space is impossible (for bladder
      or prostate surgery): a subperiosteal retropubic cleavage, either isolated or
      combined with a transperitoneal approach. (2) When the cleavage of the Bogros'
      space is impossible (for a surgery on the iliac vessels): a transperitoneal
      approach; but the prevention of the perivascular sclerosis after the use of large
      prostheses relies on the easy preservation of the funicular sheath, able to
      protect the iliac vessels, providing no slit has been done on the mesh
      prosthesis.

PMID- 9588054
TI  - [Additive medial osteotomy of the tibia locked with a coral callus. First results
      apropos of 38 operations].
AB  - We inserted a calibrated coral callus to lock addive medial osteotomy of the
      tibia in 38 patients. We followed these patients for 1 to 6 years evaluating
      clinical, radiological and histological outcome. Rehabilitation was very
      insufficient. In our later cases, the porosity of the coral insert was improved,
      apparently facilitating bone penetration.

PMID- 9588055
TI  - [Current treatment of static deformities of the great toe].
AB  - The modern techniques of treatment of the hallux valgus are founded on the
      biomechanic and permit to give again a good function of the big toe. The authors
      prefer the osseous methods and specially the phalangeal and metatarsal
      osteotomies. It is necessary also to do a lateral release of the
      metatarsophalangeal joint and an exostosectomy. The late results are good.

PMID- 9588056
TI  - [Surgical treatment of invalidating musculo-tendinous retractions in the
      dependent elderly].
AB  - The authors have reviewed 37 patients aged 64 to 91 years or their charts in the
      purpose to evaluate the results of surgical treatment of severe acquired
      contractures of arms hands and legs. They describe the deformations, surgical
      technique, morbidity, and the results. 4 patients deceased within the first week
      after surgery; morbidity was very low. The results were satisfactory: nursing was
      greatly facilitated and pain during nursing care and toilet disappeared, the
      patients could again seat in a wheel chair. They conclude that this surgery can
      be very helpful for these disabled patients.

PMID- 9588057
TI  - [Proposed methodology for calculating external forces applied on the mandible].

PMID- 9588058
TI  - [Tricalcium phosphate, vector of antibiotics: gentamycin and vancomycin. In vitro
      physicochemical characterization, study of biomaterial porosity and gentamycin
      and vancomycin elution].
AB  - We have investigated a Vancomycin and Gentamycin loaded macroporous tri-calcium
      phosphate-type beta-ceramic, Calciresorbr. Elution kinetics of Vancomycin and
      Gentamycin from spheric implants was studied by varying porosity and initial
      concentrations; then, the other following parameters, that can be modulated and
      are likely to be involved in this elution process, were analysed: Antibiotic
      charge: quantitative analysis (titration). qualitative analysis by scanning
      electron microscopy. Material's porosity: qualitative analysis: optical and
      scanning electron microscopy. quantitative analysis by stereology and treatment.
      This physicochemical characterization would favour correct manufacturing of new
      macroporous synthetic bioceramics in order to achieve satisfactory elution
      kinetics and homogenous materials.

PMID- 9588059
TI  - [Value of limited dissection of residual retroperitoneal masses after
      chemotherapy for malignant non-seminoma tumors of the testis. Apropos of 74
      cases].
AB  - Since asplatin salts have been used in chemotherapy, the efficiency of this
      treatment has changed the destiny of advanced forms of testicular cancer. The
      universally recommended treatment of post-chemotherapy residual retroperitoneal
      tumor masses is radical retroperitoneal lymph node dissection. Results of our 74
      limited expresses of these tumor masses confirm that the chosen treatment was
      appropriate. It guarantees the future and limits genital sequellae in young
      patients. It is perfectly consistent with the therapeutic history of this model
      in cancerology: precisely defined indications for the therapeutic means of a
      pluridisciplinary pool of resources always increases efficiency, reduces the need
      for invasive treatment, and limits sequellae.

PMID- 9588060
TI  - [Thyroidectomy without drainage].
AB  - Recent randomized series did not support routine prophylactic drainage after
      thyroidectomy. We undertook a prospective study in order to evaluate the
      effectiveness and the morbidity of a non drainage strategy after thyroidectomy.
      Between april 1993 and may 1995, one hundred fifty consecutive patients underwent
      thyroidectomy without drainage. During this period, two thyroid cancers were
      treated by total thyroidectomy with a modified radical neck dissection and
      drainage; they are not included in the study. Age range was 16 to 72 years. Sex
      ratio was 126F/124M. Indication for surgery was: solitary nodule (16),
      multinodular goiter (56), Graves' disease (21), toxic nodular goiter (34), cancer
      (8), retrosternal goiter (13), thyroiditis (2). The surgery done was: total
      lobectomy + isthmusectomy (15), total lobectomy + subtotal controlateral
      thyroidectomy (42), bilateral subtotal thyroidectomy (84), total thyroidectomy
      (9). Surgical technique was identical to that used previously by the author when
      drainage was installed routinely. Patients left the hospital on the first or
      second postoperative day and were reexamined on day 7 and day 30. There was no
      mortality, no suffocating hematoma, no reoperation and no laryngeal nerve
      paralysis. One patient developed a transient hypocalcemia that regressed one
      month later. Two patients developed a minor hematoma of which one disappeared
      after two weeks and the other drained spontaneously through the surgical incision
      on the seventh postoperative day. We conclude that drainage after thyroidectomy
      has no adverse effects and can be avoided if meticulous surgery is done. Absence
      of drainage simplifies the early postoperative course, improves the comfort of
      the patient, decreases hospital stay and reduces hospital cost. However, drainage
      may be of value in case of hemostatic problems or associated cervical neck
      dissection.

PMID- 9588061
TI  - [Digestive flaps and facial microsurgery].
AB  - Abdominal wall and contents can be used out of the coeliac cavity, as tissues
      donors site, for filling up or covering defects. Microsurgical technology mastery
      can extend their use in all the human body parts, especially in the craniofacial
      area. More than 110 digestive free transplants have been used during a 8 year
      period in head and neck surgical repairs. The report shows how to exploit at
      their best the anatomical and physiological properties of diverse abdominal
      tissues. Beyond this, the possible association of these transplants with other
      repair techniques opens new therapeutical perspectives, such as chimerical flaps
      whose pedicle distributes to heterogenous (or heteroclite) components, double
      flaps with a single or a double pedicle, replacing, at one single operative time,
      each missing tissue by the most adequate transplant. In consideration of this,
      abdominal tissues are an inexhaustible source of transplants, even through some
      imperfections must be managed.

PMID- 9588062
TI  - [Hospital reform and surgery. Attitude of private surgeons facing hospital
      reform].

PMID- 9588063
TI  - [The Pfannenstiel incision in colorectal surgery].
AB  - A parietal incision derived from Pfannenstiel's incision has been used since 1983
      for surgery of the left colon and rectum. We conducted a prospective study in 100
      patients with a mean age of 61 years who underwent surgery from 1984 to 1987 to
      assess the parietal outcome, postoperative pain and respiratory impact. The most
      frequent procedures were: sigmoidectomy (n = 48), anterior resection of the
      rectum (n = 24), rectopexia (n = 12), amputation of the rectum (n = 5) and total
      colectomy (n = 5). The splenic angle was mobilized in 23 cases. The operation
      also included a procedure to relieve occlusion in 4 patients. Operative mortality
      was nil. Parietal complications were bleeding (n = 4) or infection (n = 8). Seven
      early reoperations used the same access. Mean follow-up for 61 patients was 75
      months. No cases of eventration were observed despite factors predictive of
      failure. Ventilatory impact, as measured by spirometry showed ventilatory peak
      flow and blood gases comparable to those observed after a medial hypogastric
      incision. Pain, assessed on the bases of a visual analog scale and use of
      antalgesics, was considered to be mild on day 1, low on day 2 and absent on day
      5. Sixty-five percent of the patients did not require antalgesics. In conclusion,
      this incision creates a hypogastric minilaparotomy allowing midline sub- and peri
      umbilical, or even xyphoidial access with little pain and operative risk as the
      parietal risk is eliminated. Oral nutrition and activity can be resumed rapidly,
      reducing surgical stress in a protocol for minimally-invasive surgery.

PMID- 9588064
TI  - [Results of laparoscopic treatment of diverticular sigmoiditis. Apropos of 85
      cases].
AB  - The authors report their experience of laparoscopic management of sigmoid
      diverticulitis in 86 patients operated from november 1991 to december 1996. Out
      of them, 9 patients in whom sigmoiditis was revealed by an acute complication
      underwent an emergency procedure and 76 patients were operated electively. The
      mean hospital stay was 9.2 days (range 5 to 15 days) and the mean time of passage
      of flatus was 2.4 days. Benefits of laparoscopic management of sigmoid
      diverticulitis consist of improvement of early postoperative course and absence
      of abdominal wall sequelae. The decrease in mean hospital stay in not significant
      except for patients who underwent an emergency procedure.

PMID- 9588065
TI  - [Richter's spinofixation in vaginal prolapse].
AB  - The transvaginal sacrospinous fixation, called Richter operation was initially
      aimed to cure vaginal vault prolapse after hysterectomy. The results are as good
      as those of the abdominal promontory fixation with the well known advantages of
      the vaginal route. Indications way be extended to V3 U3 R3 prolapse and cure of
      elytrocele with good results in our practice. In few cases remnant cystocele may
      be a trouble some problem.

PMID- 9588066
TI  - Ventromedial nucleus of hypothalamus is related to the development of cancer
      induced anorexia: in vivo microdialysis study.
AB  - Based on reports that increased hypothalamic ventromedial nucleus (VMN)-serotonin
      (5-HT) is associated with cancer anorexia and recent findings in our laboratory
      that low levels of dopamine (DA) in the VMN are associated with prolonged inter
      meal intervals thus decreased food intake, and reports that setting up satiation
      is concomitant with descending levels of DA in the rostromedial hypothalamus, we
      hypothesized that an elevated 5-HT to low DA ratio in the VMN modulates food
      intake in cancer anorexia. METHODS: In Expt 1: A microdialysis cannula guide was
      placed stereotactically into the VMN of methylcholanthrene (MCA) sarcoma tumor
      bearing (TB) Fischer rats and in non-tumor-bearing (NTB) and pair-fed (PF)
      controls. When TB rats manifested anorexia by a decrease in food intake, VMN-5
      HT, its metabolite 5-hydroxyindolacetic acid (5-HIAA), and DA with its metabolite
      3,4,-dihydroxyphenylacetic acid (DOPAC) were measured by in vivo microdialysis
      using HPLC during baseline, in response to food, and after feeding. In Expt 2: TB
      rats had tumor removed and VMN microdialysis performed 7 days later. RESULTS:
      Increased 5-HT release and turnover, and significantly reduced DA release with
      increased DOPAC occurred in TB vs NTB or PF rats. When food was offered, intake
      in TB rats was significantly lower than in NTB control rats. During eating, VMN-5
      HT rose and peaked significantly earlier in TB vs NTB rats, while DA release was
      significantly reduced. With eating, the 5-HT and DA metabolism became reduced in
      all rats. Seven days after surgical removal of the tumor, 24 h food intake had
      increased to the level of controls; and when food was offered during
      microdialysis, intake in TB rats increased (ns relative to control), but was not
      yet normal. VMN microdialysis showed that 5-HT was normal at baseline, as well as
      during and after eating, while DA remained depressed. The metabolic turnover of 5
      HT and DA was significantly lower in TB-r and PF vs NTB rats. We conclude that
      increased 5-HT/DA ratio is related to the development of cancer-induced anorexia.

PMID- 9588067
TI  - Effect of long lasting terguride treatment on mutual relationship between glycide
      and lipid parameters in SHR/N-cp Koletsky rats.
AB  - Experiments were performed in the genetically hypertensive obese rats of Koletsky
      type (SHR/N-cp) and in their lean siblings. The effect of long lasting terguride
      treatment on glycide and lipid metabolism was monitored. Terguride decreases
      insulinemia in all groups of rats. In all groups of rats terguride increases
      tolerance glucose. Terguride increases insulin binding to erythrocytes in all
      groups of rats except SHR/N-cp obese females. The mentioned drug decreases plasma
      triglycerides in SHR/N-cp obese females. On the other hand, this drug increases
      plasma triglycerides in SHR/N-cp obese males. Correlation between basal glycemia
      and insulin binding to erythrocytes as well as between triglycerides and
      insulinemia which was found in control SHR/N-cp lean males is missing under the
      terguride treatment. Similarly, correlation between plasma triglycerides and
      insulinemia, glucose tolerance and insulinemia, basal glycemia and insulinemia,
      plasma triglycerides and basal glycemia are missing under the terguride treatment
      in SHR/N-cp lean females. Under the terguride treatment there appears correlation
      between insulin binding to erythrocytes and basal glycemia. We found in SHR/N-cp
      obese males opposite changes in number of correlations when we compare control
      and terguride animals. While in controls only one correlation was detected, i.e.,
      correlation between glucose tolerance and insulin binding to erythrocytes, then
      under the terguride treatment there appear correlations when basal glycemia is
      computed versus insulin binding to erythrocytes or to glucose tolerance and/or to
      triglycerides. Moreover, there is under the terguride treatment correlation
      insulin binding to erythrocytes versus plasma triglycerides or versus
      insulinemia. While in SHR/N-cp lean of both sexes and in SHR/N-cp obese males
      profound changes in the number of statistically significant correlation
      coefficients were found when controls are compared with animals under the
      terguride treatment, the different picture we found in SHR/N-cp obese females,
      i.e., under the terguride treatment correlation basal glycemia versus insulinemia
      or versus insulin binding to erythrocytes as well as correlation insulin binding
      to erythrocytes versus insulinemia is present in controls as well as in terguride
      treated animals. In comparison with controls under terguride only two
      correlations are missing, i.e., glucose tolerance versus insulinemia or versus
      insulin binding to erythrocytes.

PMID- 9588068
TI  - A comparison of the therapeutic efficacy of conventional and modern oximes
      against supralethal doses of highly toxic organophosphates in mice.
AB  - 1. The therapeutic efficacy of various oximes (pralidoxime, obidoxime, methoxime,
      HI-6, HLo-7, BI-6) against supralethal nerve agent poisoning (soman, sarin,
      cyclosin) in mice was tested. 2. New oxime BI-6, synthesized in our laboratory,
      is significantly more efficacious than conventional oximes but a little less
      efficacious than other H-oximes (HI-6, HLo-7). 3. H-oximes (HI-6, HLo-7) seem to
      be the most efficacious reactivators of nerve agent-inhibited
      acetylcholinesterase for antidotal treatment of supralethal nerve agent poisoning
      in mice.

PMID- 9588069
TI  - Red cell distribution width (RDW) as a marker of disease activity in patients
      with hairy cell leukemia.
AB  - Red cell distribution width (RDW) was examined in 18 patients with hairy cell
      leukemia (HCL) treated with 2-chlorodeoxyadenosine (2-CdA), in 5 patients treated
      with Interferon alpha (IFN-alpha) and in 9 patients subjected to splenectomy. Out
      of 18 patients treated with 2-CdA one patient was excluded of the study because
      of association of HCL with acquired sideroblastic anemia. In the remaining 17
      patients the mean value of RDW before therapy was 18.8% (range 13.5% to 25.0%)
      and dropped after successful therapy after 6 to 12 months to the mean value of
      13.6% (range 11.2% to 17.9%) and after 18 months to 13.4% (range 12.6% to 14.7%)
      (p = 0.00015 and p = 0.00049 respectively). The hemoglobin level increased from
      the mean value of 119 g/l (range 99 g/l to 157 g/l) before therapy to the mean
      value of 145.9 g/l (range 127 g/l to 172 g/l) after 6 to 12 months and after 18
      months to 147.8 g/l (range 132 g/l to 168 g/l) (p = 0.000017 and p = 0.00036
      respectively). The same trend was observed in the group of patients treated with
      IFN-alfa. The RDW decreased from the mean value of 21.3% (range 18.8% to 28.7%)
      to the mean value of 15.3% (range 12.4% to 16.7%), (p = 0.031). The hemoglobin
      level increased in this group of patients from the mean value of 115 g/l (range
      98 g/l to 127 g/l) to the mean value of 136 g/l (range 127 g/l to 146 g/l) (p =
      0.031). In 9 patients in complete hematologic remission 34 to 293 months after
      splenectomy the mean value of RDW was 13.9% (range 13.0% to 15.5%). CONCLUSION:
      Increased RDW in HCL is associated with active disease and is reversible after
      successful therapy. This phenomenon has not been reported in the literature yet.
      Preliminary results show that the increase of RDW may be due to the
      dyserythropoiesis.

PMID- 9588070
TI  - Mean blood pressure and velocity for calculation of ventricular systolic work.
AB  - In physiology, the mean arterial pressure is defined as an average pressure
      during one or several cardiac cycles. When calculus is not used, the mean
      pressure is approximately calculated as the diastolic pressure plus one third of
      the pulse pressure. In this article it is demonstrated that, when ventricular
      systolic work is concerned, the above definition of mean pressure must be
      replaced by a weighted average during the ejection phase of the systole. This
      gives a formula, by which a much higher estimate of the mean pressure is
      obtained.

PMID- 9588071
TI  - Aniridia, gonadoblastoma, Wilms' tumor and deletion 11p13.
AB  - An incidence of bilateral gonadoblastoma in a 23-month old, mentally retarded boy
      with congenital sporadic aniridia, undescended dysgenetic testes, deletion of a
      chromosome (11) (p1302p14.2) and a later occurring unilateral Wilms' tumor is
      reported. The patient was treated by bilateral gonadectomy, nephrectomy, and
      chemotherapy, and is alive and well five years later. Another three
      aniridia/gonablastoma observations from the literature are discussed, two of them
      without and one in combination with Wilms' tumor. Diagnosis of gonadoblastoma
      remained unsuspected in two cases until autopsy and in another two cases it was
      done at surgery. A comparison of four cases reveals common finding--aniridia,
      dysgenetic gonads, genital abnormalities, mental retardation, deletion of 11p13,
      early occurrence and bilaterality of gonadoblastoma.

PMID- 9588072
TI  - Where from and where to does the medical biology march or history of the Biology
      Department of the Faculty of Medicine in Hradec Kralove.

PMID- 9588073
TI  - [Vascular endothelium as a factor in information transfer between the
      cardiovascular and immune systems].
AB  - In health, the vascular endothelium forms a multifunctional interface between the
      circulating blood and various tissues and organs of the body. It constitutes a
      selectively permeable barrier for macromolecules, as well as a nonthrombogenic
      and nonadhesive container that actively maintains the fluidity of blood. It is a
      metabolically active endocrine organ, serving as the source of multiple factors
      and mediators that are critical for normal homeostasis. These include
      vasodilators (nitric oxide, prostacyclin, endothelium-derived hyperpolarizing
      factor), vasoconstrictors (endothelin-1, thromboxane A2, prostaglandin H2 and
      components of the renin angiotensin system), various pro- and antithrombotic
      factors (e.g. tissue factor, platelet activating factor--PAF, von Willebrand
      factor), fibrinolytic activators and inhibitors (e.g. tissue plasminogen
      activator, plasminogen activator inhibitor-1), potent arachidonate metabolites
      (prostanoids), leukocyte adhesion molecules (e.g. E-selectin, P-selectin,
      intercellular adhesion molecule-1--ICAM-1, vascular cell adhesion molecule-1-
      VCAM-1), and multiple cytokines with activities of growth stimulators and
      inhibitors, transforming growth factors, proinflammatory and antiinflammatory
      mediators, tumour necrosis factors and chemotactic factors (chemokines). Besides
      these essential activities controlling the cardiovascular system, the endothelial
      cells represent an important part of the immune system as well. They have a
      pivotal role in the initiation and development of defensive and damaging
      inflammatory responses. Therefore endothelium can be considered as being the
      central equipment for the mutual exchange of life important information between
      the cardiovascular and immune systems. This in turn is leading to rapid advances
      in understanding the pathogenesis of some of the most serious and most common
      diseases, including inflammation, atherosclerosis and hypertension. (Tab. 7, Ref.
      89.)

PMID- 9588074
TI  - [Bone changes in gastrointestinal diseases].
AB  - BACKGROUND: Gastrointestinal (GIT) diseases are a common cause of metabolic bone
      changes. The aim of the study was to indicate GIT diseases (lactose intolerance,
      non-lactose intolerance, Crohn's disease, ulcerative colitis, pancreatic
      insufficiency, states after gastric resection, chronic diseases of the liver, and
      coeliac disease) by means of literature data and the authors' own results
      coinciding with the detected low bone density and thus increased risk of
      fracture. Bone changes coinciding with GIT diseases are frequent and are commonly
      asymptomatic for a long period. CONCLUSION: In coincidence with GIT diseases the
      authors indicate the necessity of being aware of the risk of bone changes
      development and to investigate them actively. An early diagnosis aids to
      introduce preventive and therapeutical measures and to halt or at least slow down
      the origin of bone changes. (Ref. 21.)

PMID- 9588075
TI  - [Autoimmune thyroid disease in patients with type 1 diabetes mellitus].
AB  - Insulin dependent diabetes mellitus type I. (IDDM) is often connected with other
      autoimmune diseases. The most frequently concomitant disease is autoimmune
      thyroiditis. The authors present the results of the observation of 33 patients.
      The age of patients at the beginning of the study was 39.5 (24-65) years (median
      + confidential intervals). In all these patients, there were performed the
      assessment of thyroid stimulating hormone (TSH), free thyroxine (fT4), thyroid
      peroxidase antibodies (AbTPO) and TSH receptor antibodies (TRAK). An ultrasound
      examination and percutaneous aspiratory biopsy were performed in all patients.
      The control examination was realised 5 years later. In 1991, primary
      hypothyroidism due to lymphoid thyroiditis in 12.1% and autoimmune
      hyperthyroidism in 3% of all patients were found. During the observation period 2
      patients died. In 1996 the diagnosis of primary hypothyroidism in 9.6% and M.
      Graves-Basedow in 3% of all patients were confirmed. Thyroid peroxidase
      antibodies have been positive in 33.4% of all patients with primary
      hypothyroidism and they correlated with ultrasound and cytology findings. (Tab.
      3, Ref. 13.)

PMID- 9588076
TI  - [Microalbuminuria and tubular reabsorption of minerals in children with type 1
      diabetes mellitus].
AB  - BACKGROUND: The most severe late complication of microangiopathic changes in
      diabetes mellitus type I (IDDM) is the diabetic nephropathy. The fully developed
      picture of diabetic nephropathy usually does not occur in children, however,
      original signs of altered renal functions may be present already. OBJECTIVES: The
      study is aimed firstly at the detection of microalbuminuria and the relation
      between the amount of albumin urinary excretion and individual clinical indices
      such as age, degree of metabolic compensation, blood pressure. Secondly, the
      study's objective is to evaluate alterations in tubular reabsorption of minerals.
      MATERIAL AND METHODS: 1.) The occurrence of microalbuminuria has been detected on
      the basis of a four-year longitudinal clinical follow-up of 134 children (81 boys
      and 53 girls) with IDDM. Examinations which took place in regular twelve-month
      intervals were aimed at the investigation of the amount of albumin urinary
      excretion by means of radioimmunoanalysis in the collected twelve-hour night
      fraction of urine, simultaneous level of HbA1C and blood pressure values. The
      degree of the evaluated metabolic compensation during the first 5 years of
      diabetes occurrence was evaluated retrospectively and expressed as its mean
      value. 2.) 18 randomly selected patients and 12 controls were subdued to an
      examination of alterations in tubular reabsorption of minerals--sodium, calcium
      and phosphorus. RESULTS: 1.) On the basis of the amount of excreted albumin the
      children were divided into 3 groups. The first group (n = 105) consisted of
      children with normal albumin excretion, the second group (n = 13) represented
      children with transitory microalbuminuria, and the third group 16 (11.9%) were
      patients with persistent microalbuminuria. There was no significant difference
      observed in the degree of metabolic compensation between individual groups. At
      the end of investigation the diastolic blood pressure was significantly higher in
      the third group of children (76.1 +/- 0.9 and 75 +/- 1.9 or 82.8 +/- 1.8 mmHg,
      0.001). A significant correlation was found between HbA1c, systolic and diastolic
      blood pressure and the amount of urinary excretion of albumin (p < 0.001). 2.)
      The investigation of tubular balance of minerals led to the detection of a
      significantly increased tubular reabsorption of sodium and calcium in children
      with IDDM (p < 0.001), whilst the urinary excretion of these ions did not
      increase. However, there were found significantly increased values of urinary
      phosphorus excretion (p < 0.001) with its value of tubular reabsorption remaining
      unaltered. CONCLUSIONS: The alterations of glomerular functions is present
      already in the commencing stages of IDDM. The significance of examination of the
      amount of albumin urinary excretion augments after the twelfth year of age,
      during which the metabolic compensation becomes markedly deteriorated and the
      blood pressure elevates. Bad metabolic compensation with hyperglycaemia and
      glycosuria significantly influence tubular functions. This can represent the
      cause of the disturbed glomerulo-tubular balance which manifests itself by
      increased losses of phosphorus in children with IDDM. This fact can disturb
      osteogenesis in these patients. (Tab. 2, Fig. 3, Ref. 27.)

PMID- 9588077
TI  - [The spectrum of mutations in the CFTR gene in patients with cystic fibrosis in
      Slovakia].
AB  - Up to present, more than 500 mutations have been described in the CFTR gene of
      patients affected by cystic fibrosis (CF). The vast majority of them, however,
      are extremely rare, and in fact, were detected only in the original reported
      cases. This study is aimed at analysis of 9 known mutations in the CFTR gene in
      CF patients within the population of Slovakia. The region in question of the
      human genome was analysed by means of polymerase chain reaction (PCR), digestion
      with the appropriate restriction enzyme, followed by electrophoretic separation
      of generated DNA fragments. 7 different mutations were identified on 234 CF
      chromosomes, which made up 74.36% of all CF-mutations: delta F508--59.4%, G542X-
      5.56%, R553X--3.42%, N1303K--2.99%, R347P--1.71%, W1282X--0.85%, and 3849 + 10kb-
      0.43%. In 57.26% of patients mutations were identified on both homological
      chromosomes, in 33.33% on one of them, and only in 9.4% of patients there were
      none of the analysed mutations found. These results provide a good basis for the
      planning and setting up of an effective strategy for direct DNA-based diagnosis
      of CF in Slovakia. (Tab. 4, Ref. 19.)

PMID- 9588079
TI  - [Presence of Y-specific sequences in patients with Turner syndrome as a
      presymptomatic marker of increased risk of gonadoblastoma].
AB  - The risk of the origin of neoplasms in patients with gonadal dysgenesis and the
      presence of Y chromosome mosaicism has been known for a long period. The majority
      of hidden mosaicism is however not detectable by means of cytogenetic methods.
      The authors of this study deal with the detection of Y specific chromosomal
      sequences in 86 patients with Turner syndrome by means of polymerase chain
      reaction (PCR) and compare the results of this method with cytogenetic findings.
      The presence of Y specific sequences was proven in 8 patients (9.3%) which
      correlates with the results of several recent studies. In two cases, the Y
      chromosome fragment was verified also cytogenetically, in five patients, the
      diagnose was made more accurate at an originally non-specified marker, and in two
      cases, the cytogenetic examination has assessed the finding of X chromosome only.
      PCR is a more sensitive and a more precise method of the assessment of Y
      chromosome mosaicism in patients with Turner syndrome enabling more effectively
      to single out persons under the risk of rudimentary gonads gonadoblastoma
      development. (Fig. 5, Ref. 32.)

PMID- 9588078
TI  - [The effect of n-3 fatty acid administration on selected indicators of
      cardiovascular disease risk in patients with type 2 diabetes mellitus].
AB  - BACKGROUND: Serum triacylglycerols (TG), VLDL, HDL, fatty acid and eicosanoid
      spectrum are among the factors determining the risk of cardiovascular
      complications in NIDDM. N-3 polyunsaturated fatty acids (PUFA) are expected to
      have beneficial effects on these factors. In NIDDM patients there have however
      been previously reported (late 1980s) some adverse effects. OBJECTIVES: Our aim
      was to verify the effects of n-3 PUFA in NIDDM patients using relatively low
      dosage. METHODS: The investigated group included 21 NIDDM patients with
      dyslipoproteinemia type IV. The patients were treated for 28 days with 1.7 g EPA
      (eicosapentaenoic acid) + 1.15 g DHA (docosahexaenoic acid)/day (10 capsules/day
      of MAXEPA, Seven Seas U.K.). The lipoproteins were measured using the BIO-LACHEMA
      kits, the fatty acid spectrum in phospholipids was determined by gas
      chromatography and prostanoids (after their separation) were measured by RIA
      methods. MAIN RESULTS AND CONCLUSIONS: After the MAXEPA treatment there has been
      a strong decrease in TG (p < 0.005) and VLDL (p < 0.002) serum levels,
      accompanied by a significant increase in HDL (p < 0.02). The final-to-baseline TG
      ratio in individual patients negatively correlated with the relative percentage
      of EPA in phospholipids after the treatment (p < 0.03; r = -0.474). There was no
      significant change in serum total cholesterol, fasting glycaemia and glycosylated
      hemoglobin. There was a slight, but statistically already significant (p < 0.05),
      rise in LDL. The relative percentage of EPA, docosapentaenoic acid and DHA in
      serum phospholipids increased sharply (p < 0.001, p < 0.001, p < 0.001). The
      increase of n-3 PUFA in individual patients was linked with the decrease in n-6
      PUFA (p < 0.001; r = -0.686). The spectrum of the latter has changed also very
      markedly. The prostacyclin PGI2-to-thromboxane TxA2 ratio increased significantly
      (p < 0.001). Beneficial effects of n-3 fatty acids have prevailed and this kind
      of treatment seems very encouraging also in NIDDM patients. The results are
      logically compatible with other authors' results pattern formed in 1990s. A
      slight rise in serum LDL needs a more detailed discussion since only its
      phenotype B ("small dense LDL particles") has been recently found to be
      atherogenic. (Tab. 2, Fig. 5, Ref. 15.)

PMID- 9588080
TI  - [Production of IL-8 by the THP-1 monocyte cell line is regulated differently by
      cyclosporin and retinoic acid].
AB  - Chemokines play a very important role in inflammation and belong to the family of
      proinflammatory cytokines. They preferentially act on neutrophiles and have no
      activity on monocytes and eosinophiles. IL-8 is a member of C-X-C chemokines. The
      IL-8 level is about 150-times higher in the psoriasis affected skin. It suggests
      that IL-8 may play an important role in the pathogenesis of psoriasis. The
      precise mechanism of cyclosporine (CsA) and retinoic acid (RA) effects are not
      known. The aim of the experiment was to find out CsA effect and RA effect on
      production of IL-8 by THP-1 cell line. THP-1 cell line was cultivated in
      completed RPMI-1640 medium and stimulated with LPS. The level of IL-8 was
      evaluated by human ELISA kits. Student's test was used for statistical analysis.
      It was found out that CsA inhibits IL-8 production by stimulated THP-1 monocyte
      cell line in dose dependence course. RA promotes IL-8 production by stimulated
      THP-1 monocyte cell line in dose dependence course. Preincubation experiments
      with CsA and RA confirmed the previously found effects of these drugs. CsA did
      not demonstrate cytotoxic effect on THP-1 cell line. (Fig. 7, Tab. 6, Ref. 17.)

PMID- 9588081
TI  - [Frequency of the HLA-DPB1 allele in the Slovak population].
AB  - The polymorphism at the HLA-DPB1 locus was established in 146 unrelated persons.
      The polymerase chain reaction (PCR) in combination with restriction fragment
      length polymorphism (RFLP) technique was used. After PCR amplification of the
      second exon of the HLA-DPB1 locus, the PCR products were digested with seven
      allele specific endonucleases. The alleles DPB1*0401 (43.29%), DPB1*0402
      (20.89%), DPB1*0201 (14.39%) and DPB1*0301 (9.25%) were the most common among 15
      DPB1 alleles detected in the tested group. The least frequent alleles were DPB1
      *0202, *0601, *1101 and *1501 (0.34%). The comparison with allele frequencies in
      Austrian and German populations showed no statistically significant differences.
      (Tab. 2, Ref. 18.)

PMID- 9588082
TI  - [Positive effects of essential phospholipids and improvement of life style in
      patients with toxic liver injury].
AB  - Within an open, non-randomized clinical study, the authors investigated the
      effect of a three-month therapy by a standard product of so-called essential
      phospholipids in a group of patients (31 men and 2 women, average age being 45.6
      +/- 10.8 years) with toxic liver damage--steatosis and steatohepatitis which have
      developed after exposure to the polychlorinated phenols and cresols, or other
      potentially toxic chemical substances occurring in working environment and/or
      exposition to alcohol. The therapy included a recommended change in life routine
      with a decrease in alcohol consumption, or entire exclusion of alcohol abuse.
      Within the process of observation, the authors used non-invasive methods
      (clinical examinations, laboratory examinations, ultrasonographic examination). A
      special attention was paid to the evaluation of the biotransformation capacity
      the liver and the assessment of spartein-debrisoquin-dextromethorphan metabolic
      fenotype. The results of investigation indicated: (1) significant improvement of
      the subjective status of the treated patients associated with an improvement of
      ultrasonographic findings of liver steatosis, trend of withdrawal of biochemical
      activity indices and favourable development of the biotransformation capacity of
      the liver in a majority of the investigated patients. (2) A very good tolerance
      of the administered drug without adverse effects. The use of non-invasive
      surrogate markers in coincidence with clinical investigation of the effect of
      applied medicamentous therapy in patients with chronic liver diseases represents
      a methodic increase in current modest options of evaluation of effectively and
      safety of the new therapeutic procedures in clinical hepato-pharmacology. (Tab.
      5, Ref. 42.)

PMID- 9588083
TI  - [Treatment of portal hypertension].
AB  - The therapy of portal hypertension depends to a significant extent on its
      clinical manifestation. In cases of acute haemorrhage from oesophageal varices in
      patients with portal hypertension, the objective of the therapy is to stop the
      haemorrhage (endoscopically, or by compression by means of a balloon probe) and
      to decrease the pressure and the reflux within the portal vascular bed. Urgent
      sclerotisation under the simultanous pharmacologic decrease of portal
      hypertension is successful in 93-95%. There is an alternative procedure residing
      in introducing a balloon probe for several hours and subsequent repeated
      sclerotisation until a complete eradication of varices is achieved regarding the
      prevention of haemorrhage exacerbation. Urgent surgical solution is on the basis
      of the results of various investigated studies reserved for patients in whom
      endoscopic sclerotisation was not successful. Indication of surgical therapy must
      be also deliberated in candidates for liver transplantation, regarding the
      possible consequent technical problems after some types of interventions.
      Endoscopic sclerotisation of oesophageal varices is also an appropriate
      preparation for transplantation of the liver in patients with liver cirrhosis
      included into the transplantation programme. TIPS is a perspective new method in
      the therapy of portal hypertension of both, non-bleeding varices, as well as in
      other indications. It is also a certain intermediating link in therapy in some
      patients with liver cirrhosis on the waiting list of candidates for liver
      transplantation. Pharmacotherapy is a significant part of the portal hypertension
      therapy. It is appropriate to combine the endoscopic treatment with
      pharmacotherapy of portal hypertension in both, cases of acute haemorrhage, as
      well as in the prevention of haemorrhage exacerbation. In cases of acute
      haemorrhage, the combination of glypressin with nitroglycerin is justified, as
      well as the therapy by somatostatin. The prevention of haemorrhage exacerbations
      uses a whole series of vasoactive substances, especially nitrates, beta-blockers
      and ACE inhibitors. The prevention of the first bleeding includes the
      prophylactic therapy (endoscopic, pharmacologic, or surgical) recommended only in
      a selected group of patients under high risk of bleeding. The possible
      perspective option will reside especially in the combined pharmacological
      therapy, the fact of which will have to be proven in the future. (Fig. 1, Ref.
      25.)

PMID- 9588084
TI  - [Co-localization of substance P and NADPH-d in the thoracic spinal cord of
      rabbits].
AB  - In this study we have demonstrated the localization of substance P (SP) and
      nitric oxide (NO), in the thoracic spinal cord of rabbit. SP was concentrated in
      the dorsal horn of the spinal cord, mostly in the superficial layers (LI, LII),
      around the central canal (LX), and in the region of intermedia-lateral nucleus
      (IML nc.). NADPH-d (nicotinamide adenine dinucleotide phosphate diaphorase) is an
      enzyme, which proves the presence of NO. The highest concentration of NADPH-d
      positive structures were found in the same regions as the SP-positivity. SP is
      suggested to play a role in the nociceptive transmission. Localization of NADPH-d
      revealed also the fact that NO may be involved in nociceptive transmission in the
      spinal cord. Close association of sympathetic preganglionic neurons and fibers
      with SP and NADPH-d positive structures suggest a role of these neurotransmitters
      in the modulation of sympathetic activity. (Fig. 11, Ref. 18.)

PMID- 9588085
TI  - [The effect of local ionizing irradiation on the presence of acetylcholinesterase
      positive nerve fibers in the spleen of rats].
AB  - Changes in the distribution of ACHE-positive nerve fibres in the spleen of the
      rat after local irradiation have been studied by light microscopy using direct
      tiocholin method of El-Badawi and Schenk (1967). ACHE-positive nerve fibers enter
      the spleen in the vicinity of splenic artery branches and they are gradually
      distributed in form of perivascular plexuses in the white pulp to the
      periarterial lymphatic sheath (PALS). One dose of local irradiation of the head
      of the rat causes changes in the presence and distribution of the ACHE-positive
      nerve fibres in the spleen of the rat. After an intense decrease or the absence
      of these fibres during the period of the first days after irradiation, there is
      an evident restoration of ACHE-positive nerve fibres in the white pulp of the
      organ. The distribution and topography of these nerve structures is the same as
      in non-irradiated rats on the 35th day after irradiation. During the following
      days, there is another evident decrease in ACHE-positive nerve fibres in all
      described localizations of the spleen. Our findings suggest that the indirect
      effect of irradiation can affect some changes in innervation of the organ which
      was not exposed to its direct influence. (Fig. 3, Ref. 13.)

PMID- 9588086
TI  - The effect of ambroxol on the vascular reactivity in the rabbit.
AB  - Experiments were designed to determine whether ambroxol, a drug used for the
      treatment of respiratory disorders, affects the basal tension and/or contractions
      due to adrenergic stimuli in the isolated rabbit portal vein and pulmonary
      artery. Ambroxol in concentrations of 10(-6)-10(-4) mol/l produced a
      concentration-dependent increase in basal tension, but a decrease in spontaneous
      mechanical activity of portal vein. The same concentrations of ambroxol failed to
      influence basal tension of pulmonary artery. However, when the vessel tone was
      increased by exogenous noradrenaline, ambroxol elicited concentration-dependent
      contractions also in this vessel. Moreover, ambroxol in the concentration of 10(
      5) mol/l significantly enhanced vascular contractions due to both exo- and
      endogenous noradrenaline. The results suggest that ambroxol, in biologically
      relevant concentrations, may influence or even induce vascular contractions to
      adrenergic stimuli. Their expression, however, depend on the type of vascular
      smooth muscle. (Fig. 7, Ref. 25.)

PMID- 9588087
TI  - [Localization of NADPH-d positive cells in the thymus of pheasants and mice].
AB  - The presented study was designed to clarify the localization and distribution of
      nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity, a
      marker of NO synthase, in pheasant and mouse thymuses. To provide a morphological
      basis for understanding the role of nitric oxide (NO) in the thymus. The NADPH-d
      histochemistry revealed dark blue stained cell structures. In the pheasant
      thymus, NADPH-d positive cells were present as clusters which were distributed in
      the medulla and the corticomedullar area. NADPH-d positive cells were observed
      mostly in the medulla of the mouse thymus. They were round, oval or irregular in
      shape, with various intensity of staining. There were found NADPH-d positive
      nerve fibres in the perivascular location in both groups of experimental animals.
      (Fig. 4, Ref. 14.)

PMID- 9588088
TI  - [Herbal polysaccharides in the treatment of coughs].
AB  - BACKGROUND: Because of serious adverse effects of centrally acting antitussive
      agents, is necessary to find new drugs with cough-suppressing activity. Medicinal
      herbs are a potential source of polysaccharides with high antitussive efficiency
      and on the other with minimal side effects. AIM: The study was to assess the
      antitussive action of mixture of a polysaccharides (RL) and polysaccharide-xylan
      (XY), both isolated from above-ground parts of Rudbeckie fulgida var.
      sullivantii. The observed activity was compared to those of narcotic and
      nonnarcotic antitussive substances used in clinical practice. METHODS: Cough was
      evoked by mechanical irritation of the airways in nonanaesthetized cats with
      chronic tracheal cannuly. The plant substances were administered perorally in the
      dose of 50 mg per kg body weight. RESULTS: Results indicate, that administration
      of RL induced a suppression of the followed cough parameters from both areas of
      airways (total fall in cough parameters by 46.6%). Administration of xylan
      induced the fall in the followed cough parameters with more significant influence
      on the laryngopharyngeal area of the airways (total fall in cough parameters
      48.2%). CONCLUSION: Administration of RL and xylan did not achieve the effect of
      codeine, but had a more intensive antitussive effect than the peripherally acting
      droprozine and prenoxdiazine. (Fig. 3, Ref. 11.)

PMID- 9588089
TI  - [Ambroxol and protective reflexes of the respiratory tract].
AB  - BACKGROUND: Ambroxol, trans-4-/(2-amino-3,5-dibromobenzyl) amino/cyclohexanol
      hydrochloride, a drug used to increase surfactant secretion in the lungs, has
      been reported to be effective in reducing exacerbation of chronic bronchitis and
      in the protection from inflammatory reactions (Bianchi et al., 1990). The effect
      of this drug on the defence reflexes of airways remains unknown. AIM: The aim of
      this study was to follow the changes in the cough reflex after administration of
      ambroxol in the dose of 10 mg/kg body weight. Ambroxol was administered i.p. and
      perorally. Further, we investigated the bronchodilatory activity of ambroxol.
      METHODS: In the present study, the effects of ambroxol on the cough reflex in the
      cats were investigated. The drug was administered intraperitoneally and perorally
      in the dose of 10 mg/kg body weight. Cough was induced by mechanical stimulation
      of airways. The effect of ambroxol on the smooth muscles of guinea pig (weight
      300-400 g) airways was investigated in vitro. The contractions were induced by
      carbachol in the concentration of 10(-5) mol/l and by histamine in the same
      concentration. RESULTS: The results indicate that ambroxol, when administered
      intraperitoneally attained a total fall in cough parameters by about 51.6%.
      Ambroxol, when administered perorally suppressed all cough parameters by about
      37.04%. Further, ambroxol has no effect on carbachol-induced contraction of
      smooth muscles of airways. The histamine-induced contraction of tracheal smooth
      muscles was significantly reduced after administration of ambroxol in the
      concentration of 10(-4) mol/l. The lung smooth muscles of guinea pig became
      relaxed after administration of the drug in the concentrations of 10(-5)-10(-4)
      mol/l. CONCLUSION: The study suggests, that ambroxol has a cough-suppressive
      effect. More expressive effect of the drug on smooth muscles of airways was found
      out in case of histamine-induced contraction. (Fig. 6, Ref. 13.)

PMID- 9588090
TI  - [Anti-reflux surgery of the popliteal vein].
AB  - Any effective therapy of chronic vein insufficiency resides in the replacement or
      at least reduction of the pathological reflux causing venous hypertension. The
      aim of our study is to indicate the significance of the reconstruction of the
      damaged valves in the profound venous system, namely in the most critical
      popliteal area. On the basis of the experimental works of Wilson et al. (1991) we
      have introduced his technique of anti-reflux operation by the technique of
      invagination after the prolongation of the popliteal vein by three-fold average
      of its diameter by means of the axillary vein with a valve. This operation was
      performed in 6 patients on 7 veins. The operation lasted 3 hours in average
      without marked operative and post-operative complications. On the seventh day
      after operation, the full sufficiency is investigated by means of descendent
      phlebography in 5 newly formed valves and in two valves a particular
      insufficiency is developed. 4 patients yield a full recovery of ulcers, one
      patient slipped out from evidence, however sclerotisation of insufficient
      perforators leads quickly to recovery of dermal defects. Reconstruction of
      prothrombotically damaged valves is practically impossible and thus,
      valvuloplastic operation constructed from vascular wall in the target segment is
      not only possible but effective at the same time. (Fig. 3, Ref. 13.)

PMID- 9588091
TI  - [Ambulatory blood pressure monitoring during hypertension therapy].

PMID- 9588092
TI  - [The effect of plasma lipoproteins on the secretion of prostanoids in endothelial
      cells in vitro].

PMID- 9588093
TI  - [Changes in forearm microcirculation in patients with focal cerebral ischemia].

PMID- 9588094
TI  - [Approaches in the prevention of STD as related to the status of HIV/AIDS
      infection among prostitutes in Holland].

PMID- 9588095
TI  - [Dendrites, neurons and simulation models].
AB  - The dendritic tree, this morphologically remarkably structured and typically
      diversified portion of the neuron reveals gradually its till recently little
      known complex functional possibilities. The size of the dendritic membrane
      participates in the latter similarly as their morphological pattern and their
      electronic structure which has a marked effect also due to its passive cable
      properties on the spread and interaction of potential changes on the membrane.
      Moreover the presence of a complex, differentiated mosaic of ion channels of
      different types provides dendrites with non-linearities with a wide scope of
      dynamic phenomena and active properties. The dendritic membrane can e.g. actively
      reinforce signals proceeding along the thin dendrite fibres and may make the
      development of action potentials or their retrograde movement from the membrane
      of the cell body possible. The possible operations above the spatial and temporal
      structures of signals equipped by differently located excitation and inhibition
      synapses are enriched by the action of ions entering via ion channels into the
      cell when the membrane potential changes. Manifestations of neuroplasticity lend
      these properties further temporal and functional dimensions. The neuron is no
      longer a one-way polarized and passive transmitter of synaptic input signals four
      output action potentials; it is a complicated non-linear hierarchic dynamic
      system with possible complex temporal and spatial analogue signal transformations
      in dendritic structures. New findings are the result of the cooperative use of
      empirical and theoretical procedures based on the morphophysiological methods
      with a high differentiating capacity and the methodology of studies of dynamic
      systems and computer simulation.

PMID- 9588096
TI  - [The present and future of treatment with oral antidiabetic agents].
AB  - Oral antidiabetics (PAD) are still the most frequent pharmacotherapeutic
      intervention in NIDDM, characterized by insulin deficiency and in particular by
      insulin resistance in the liver and peripheral tissues. Depending on the site of
      action, they are divided into substances retarding carbohydrate breakdown in the
      small intestine (alpha-glucosidase inhibitors), substances stimulating B-cells of
      the islets of Langerhans (beta-cytotropic substances) and substances acting in
      the periphery. The authors discuss PAD, in particular SU and biguanides which
      have been used for treatment for some years and more recent preparations-
      acarbose (Glucobay) and miglitol. Attention is paid to perspective preparation
      which are in the research stage, among them in particular troglitazone which
      belongs into the group of substances which improve the sensitivity of insulin
      receptors (insulin sensitizers) which will soon be on the market. As to other
      possibilities the authors discuss the role of fatty acid oxidation and its
      inhibitors and new non-sulphonyl urea insulin secretagogues. All these
      preparations, despite certain limitations, offer exciting therapeutic
      perspectives. Further research will reveal to what extent this potential can be
      implemented in practice.

PMID- 9588097
TI  - [Hypertonic-hyperoncotic volume replacement with Tensitone].
AB  - BACKGROUND: The use of hypertonic-hyperoncotic solutions (HHS) is a modern method
      of volume restoration in hypovolaemias of different etiology. The objective of
      the present work was to evaluate the effectiveness and safety of the hypertonic
      hyperoncotic plasma expander Tensitone (7.5% NaCl in 6% dextran 70, Infusia a.s.,
      CR) in patients with a massive acute blood loss. METHODS AND RESULTS: In a
      multicentre clinical study the authors investigated the effect of a rapid
      infusion of a small volume of tensitone (4 ml/kg) on the restoration of basic
      haemodynamic parameters, diuresis and the general condition of 81 patients with
      massive traumatic or peroperative haemorrhage. As compared with the effect of
      standard volume expanders (N = 34), Tensitone had a markedly more rapid and more
      pronounced effect on the normalization of the blood pressure (p < 0.01), heart
      rate (p < 0.05), central venous pressure and diuresis (p < 0.01). The
      haemodynamic effects of Tensitone are almost immediate (rise of blood pressure
      within 10 minutes) while they are at the same time sufficiently protracted (for
      at least 2 hours). The tolerance and safety of treatment were very good, more
      serious undesirable effects (thrombophlebitis) were recorded only in 3.6% of the
      patients. CONCLUSIONS: Tensitone is an effective and safe preparation for rapid
      small volume resuscitation. Its use is consistent with modern trends in intensive
      care and acute medicine.

PMID- 9588098
TI  - [Angiotensin-converting enzyme inhibitors. Familiar drugs--new indications].
AB  - Angiotensin converting enzyme inhibitors (ACE) have become an important part in
      the pharmacotherapy of hypertension, in this indication they were used for the
      first time in the eighties. Later the indication was extended to heart failure
      (where they evidently reduce the mortality), acute myocardial infarction (there
      they prevent cardiac remodelling), and in myocarditis (vasodilatation, effect on
      spasms and on free oxygen radicals). As to non-cardiological indications the most
      important indications are nephrological-diabetic and non-diabetic nephropathies.
      Nowadays already different types of ACE inhibitors are available. They differ as
      to their chemical structure (they contain a sulphydryl or carboxyl group in the
      molecule, they are proline derivatives etc.) as well as by other properties
      (lipophilia, specificity, absorption rate, period of action). The authors gives a
      list of preparations encountered most frequently on our market and they discuss
      non obvious indications.

PMID- 9588099
TI  - [Radiosurgical hypophysectomy in painful bone metastases of breast carcinoma].
AB  - Radiosurgical hypophysectomy using Leksell gamma knife was performed to the
      patient with cancer pain from bone metastases of the breast cancer, relief of the
      pain was achieved. Patient survived 26 months after hypophysectomy. Review of the
      literature concerning relief of the pain after hypophysectomy is presented.

PMID- 9588100
TI  - [Genes stimulated by tissue hypoxia].
AB  - Hypoxia is a frequent pathogenetic stimulus to which the whole organism as well
      as affected tissues and cells respond by various adaptive mechanisms. The basis
      of these reactions is the ability of cells to monitor the concentration of oxygen
      molecules by oxygen sensors. Some of these reactions are the result of the
      association of the oxygen sensor of the cell with its genome. This association
      makes it possible to enhance the activity or activation of some genes. Products
      of these genes increase the resistance of cells to hypoxia, they induce an
      increased vascularization of the affected tissue, increased erythrocyte
      production and some other reactions. In tumour hypoxia can cause by this
      mechanism changes of its properties and its malignization.

PMID- 9588101
TI  - [Congenital and acquired methemoglobinemia and its therapy].
AB  - The hemoglobin (Hb) function is to bear oxygen. Hb is under the exposition of
      high oxygen concentration in the lung capillaries and it is very slowly oxidated
      to methemoglobin (MetHb) which is not able to bear oxygen. Enzymatic equipment of
      erythrocyte protects Fe2+ in HEM in front of the oxidation to Fe3+. It is created
      3% of MetHb daily. This action is considered to be autooxidation and it is
      simultaneously reduced by creation of "complex formation" of MetHb and cytochrome
      b5. The physiological level of MetHb is 0-2% in the peripheral blood. The MetHb
      level is enhanced by hereditary impairment of the erythrocyte enzyme apparatus or
      by changed Hb structure. The patients have enhanced MetHb level in peripheral
      blood in the range of 1-30%. The only symptom which is created is peripheral
      cyanosis with neither subjective nor objective difficulties. The patients do not
      require any treatment. They are very sensitive on receipt of oxidative agents.
      Occurrence of acquired methemoglobinemia is more frequent in clinical praxis.
      Administration of oxidative agents is the reason of the disease. The most
      frequent oxidative agents are sulfones, local anesthetics, enhanced contents of
      nitrates in vegetables from unsuitable manure soil. The acquired
      methemoglobinemia causes minimal clinical problems depending on the doses of
      administered drug and abates after its discontinuation quickly. Only occasionally
      it causes clinically expressive symptoms. The level above 10% of MetHb causes
      peripheral cyanosis. The level of MetHb higher than 35% causes general symptoms
      which are results of the tissue hypoxia. The level about 70% of MetHb is
      associated with coma and may have fatal outcome. When the level of MetHb is not
      very high it abates after discontinuation of the administration of causative
      drug. In the case of high level of MetHb the drug of choice is administration of
      hyperbaric oxygen, methylene blue, ascorbic acid intravenously or riboflavin in
      high doses. In the case of deficit of glucoso-6-phosphate-dehydrogenase the
      administration of methylene blue is contraindicated, because of worsen of the
      methemoglobinemia.

PMID- 9588102
TI  - [The method of calculating the numeric value of the KT/V index in the evaluation
      of effectiveness of peritoneal dialysis].
AB  - BACKGROUND: For evaluation of the adequacy of peritoneal and haemodialyzation
      treatment the BP/V index is used. In the literature there is so far no uniform
      view on the procedure of calculation. The objective was to test whether and to
      what extent the results of different procedures differ. METHODS AND RESULTS: The
      authors demonstrated that the method of calculation of this index has a marked
      impact on the result. The greatest discrepancy was due to differences in the
      distribution volume of urea (or total body water) where the mean difference was
      10% of the absolute value. Also the procedure used to assess the residual renal
      function can influence the result. Differences due to the method of collection of
      the dialysate for assessment of the urea concentration are insignificant. The
      mean difference between the maximal and minimal BP/V index, when different
      methods of calculation are used, was in the same patient 0.45, which is cca 25%
      of the total value. CONCLUSIONS: The BP/V index must be assessed always by the
      same method with maximum accuracy. When presenting results or comparing results
      of different departments, the method of calculation must be stated.

PMID- 9588103
TI  - [Clinical aspects of use of angiotensin-converting enzyme inhibitors in patients
      with arterial hypertension].
AB  - The submitted paper deals with the use of ACEI in the treatment of arterial
      hypertension. The author lists different representatives of ACEI, incl. recent
      substances. He mentions the basic strategy of treatment incl. clinical
      indications for the use of ACEI in hypertension and suitable and less suitable
      drug combinations. He gives briefly also further indications of ACEI treatment in
      patients with arterial hypertension and concomitant diseases. In the conclusion
      he deals with the most frequent side-effects of, absolute and relative
      contraindications of ACEI.

PMID- 9588104
TI  - [Enteroclysis in the diagnosis of tumors of the cecum and ascending colon].
AB  - In two patients examination of the small intestine by enteroclysis was indicated
      on account of haemorrhage into the digestive tract and severe anaemia and in one
      patient the ultrasonographic picture arousing suspicion of Crohn's disease of the
      terminal ileum. Although in all instances previously colonoscopy was made,
      considered complete, in one instance also irrigoscopy, with a negative result,
      enteroclysis revealed and surgery confirmed extensive carcinomas of the caecum
      and colon ascendens. The authors discuss the value and problems of the applied
      diagnostic method.

PMID- 9588105
TI  - Chemists, physicians, and changing perspectives on the scientific revolution.
AB  - Positivism in the history of science and medicine was challenged by Walter Pagel
      more than fifty years ago. He sought to understand early modern figures such as
      Harvey, Paracelsus, and van Helmont by looking at all their work, including
      nonscientific material generally ignored by other scholars. Of special importance
      in the sixteenth and seventeenth centuries was the chemistry found in the
      writings of Paracelsus and his followers. These "chemical philosophers" offered a
      new philosophy based on chemistry and chemical analogies that was to replace the
      works of the ancients. As physicians, they debated first with Galenists and
      Aristotelians and later with mechanists. The essay argues that these debates were
      an essential chapter in the development of the Scientific Revolution and
      important for understanding the Chemical Revolution of the eighteenth century.

PMID- 9588106
TI  - Relationship between cell counts in bovine milk and the presence of mastitis
      pathogens (yeasts and bacteria).
AB  - Bovine mastitis is an economically important disease in dairy industry and a
      variety of pathogen microorganisms are involved. The AA carried out a study to
      investigate the prevalence of yeasts and bacteria in milk samples (794) from
      dairy cows of Umbria (Central Italy), belonging to 19 herds, and the relationship
      between cell counts in bovine milk and the presence of these pathogens. 29.7%
      milk samples were positive for pathogen microorganisms, of those 4.9% were
      positive for yeasts and bacteria, 4.4% for yeasts and 20.4% for bacteria. The
      species of yeasts and bacteria most frequently encountered were Trichosporon
      capitatum (31.2%), T. beigelii (18.72%) and Candida albicans (12.48%), C.
      guillermondii (12.48%), C. tropicalis (12.48%); with regard to bacteria were
      Staphylococcus aureus (34.3%) and S. albo (19.8%). The presence of yeasts and
      bacteria in milk samples are correlated to an increase of somatic cell counts
      even if with different degree. Epidemiological and sanitary correlation were
      carried out.

PMID- 9588107
TI  - Enzyme linked immunosorbent assay for potency testing of vaccines containing
      Clostridium perfringens type D epsilon-toxoid.
AB  - For ethical, economic and technical reasons in vivo assays need to be replaced in
      routine laboratory procedures. Based on a method which is already accepted by the
      British authorities, an indirect ELISA has been developed and evaluated for
      Clostridium perfringens type D-containing vaccines. Individual and pooled sera of
      vaccinated rabbits were tested at a single dilution level, the results
      transferred into IU/ml, and compared with the conventional toxin neutralization
      test in mice. The ELISA was found to give reproducible estimates of antitoxin
      levels and showed good correlation with the conventional in vivo test in mice.

PMID- 9588108
TI  - A pathological and immunohistochemical study of goat kids undergoing septicaemic
      disease caused by Mycoplasma capricolum subsp. capricolum, Mycoplasma mycoides
      subsp. capri and Mycoplasma mycoides subsp. mycoides (large colony type).
AB  - This paper studies the pathological and immunohistochemical findings in 12 kids
      experimentally infected with Mycoplasma capricolum subsp. capricolum (Mcc), M.
      mycoides subsp. capri (Mmc) and M. mycoides subsp. mycoides (large colony type),
      (MmmLC). For the demonstration of Mcc, Mmc and MmmLC antigens an immunoperoxidase
      technique based on the labelled streptavidin biotin method was used in the 12
      kids inoculated with mycoplasmas and the three control kids inoculated with
      mycoplasma medium. All 12 kids, inoculated by different routes, developed
      subcutaneous swelling at the point of inoculation and terminated in fatal
      septicaemia from 1 to 5 days post inoculation. The histopathological findings
      consisted of cellulitis at the point of inoculation, acute diffuse interstitial
      pneumonia, arthritis and multifocal necrotic purulent splenitis in some kids. The
      Mcc, Mmc and MmmLC antigens were detected immunohistochemically in all kids with
      specific punctiform labelling inside the cytoplasm of the leucocytes or
      extracellularly at the inoculation point, respiratory airways, spleen, liver,
      joints, tonsils and lymph nodes. The results obtained in this study showed that
      the inoculation of these mycoplasmas by parenteral routes caused mycoplasmaemia.
      Moreover, the immunohistochemical results appear fully to confirm that the
      mycoplasmas were the cause of the death of the kids because of a septicaemic
      state.

PMID- 9588109
TI  - Type IV hypersensitivity in the pathogenesis of FIPV-induced lesions.
AB  - In focal lesions of feline infectious peritonitis (FIP), the cells involved in
      the delayed-type hypersensitivity were identified in formalin-fixed paraffin
      embedded and frozen samples taken from 35 affected cats. The clinical diagnosis
      of FIP was confirmed by necropsy, histology and direct immunofluorescence against
      the coronaviruses on cryostatic sections. The immune cells were detected
      immunohistochemically by the Avidin-Biotin-Complex (ABC) method using either
      polyclonal antibodies against lymphoid antigens (CD3) or monoclonal antibodies
      against lymphoid (PAN-T, CD4, CD8) and myeloid antigens (MAC387). Better
      identification of T cells and macrophages was found on formalin-fixed paraffin
      embedded sections than on cryostatic ones, while T lymphocyte subpopulations
      could be differentiated only in cryostatic sections. Type IV hypersensitivity was
      detected in focal feline infectious peritonitis virus (FIPV)-induced lesions from
      progressive activation of T lymphocytes, mainly CD4+, and the presence of
      granulocytes and macrophages. The FIPV-induced lesions could be studied as
      examples of granulomas caused by unconventional antigens, such as viruses or
      immune complexes.

PMID- 9588110
TI  - Factors influencing adherence of Streptococcus dysgalactiae to bovine mammary
      epithelial cell monolayers.
AB  - Factors that affected adherence of Streptococcus dysgalactiae to monolayers of
      primary bovine mammary epithelial cells and to a bovine mammary epithelial
      transformed cell line were evaluated. Cell culture medium inhibited more than 99%
      of binding of S. dysgalactiae to plastic and was as effective as several blocking
      agents in decreasing adventitious adherence of this organism to plastic.
      Adherence of two strains of S. dysgalactiae (UT516 and UT519) was higher to a
      transformed mammary epithelial cell line (2.85% and 0.83%, respectively) than to
      primary bovine mammary epithelial cells (0.45% and 0.52%, respectively).
      Measurement of the extent of bacterial adherence to cell monolayers showed that
      adherence was affected by inoculum size. This indicated that the process was
      mediated by saturable cell receptors and allowed selection of bacteria:epithelial
      cell ratios not approaching saturating conditions (< 1500:1). In addition,
      reduction of bacterial adherence by more than 90% following cell fixation
      indicated that cell surface proteins played a major role in this process.
      Delineation of bacterial and epithelial cell factors influencing adherence of S.
      dysgalactiae to mammary epithelial cell monolayers resulted in the development of
      an in vitro method for quantifying bacterial adherence to cell monolayers.

PMID- 9588112
TI  - Serologic diagnosis of ovine lentiviruses by whole virus ELISA and AGID test.
AB  - Enzyme-linked immunosorbent assay (ELISA) and agar gel immunodiffusion (AGID) are
      the most widely used serological tests for Maedi-Visna diagnostics. The purpose
      of the present study was to develop an indirect whole virus ELISA and an
      immunodiffusion test and compare their sensitivity. A total of 747 ovine serum
      specimens were analysed for antibodies against this ovine lentivirus. The number
      of positive results in the ELISA was 430 (57.56%). In the AGID test, a positive
      result was found in 380 samples (50.87%). In the group of discordant results 78
      (10.4%) samples tested positive by the ELISA and negative by the AGID test and 28
      sera (3.7%) were found to be positive by the AGID test and negative by the ELISA.
      The data in this report show the ELISA to be more sensitive than the AGID test,
      but accurate serological diagnostics should be based on a combination of the two
      tests.

PMID- 9588111
TI  - Fumonisin B1 contamination of maize and experimental acute fumonisin toxicosis in
      pigs.
AB  - The fumonisin B1 content of 69 visibly mouldy and 23 mould-free maize samples
      grown in Hungary in 1993-1995 was determined by high-performance liquid
      chromatography (HPLC). Fumonisin B1 was found to occur in 70-73% of the mouldy
      samples. The mycotoxin level increased from year to year: the highest fumonisin
      B1 concentration was 75.1 mg/kg. The samples that were mould-free on visual
      inspection showed a much lower prevalence of fumonisin B1 contamination (30%) and
      contained fumonisin B1 in markedly lower concentrations (average, 1.52 mg/kg;
      maximum concentration, 5.1 mg/kg). Using the Fusarium moniliforme strain
      designated 14/A, isolated from the sample that had the highest mycotoxin
      concentrations, fumonisin B1 toxin was produced on maize by an internationally
      accepted procedure. Subsequently, two weaned piglets were fed a diet containing
      330 mg fumonisin B1 per kg of feed. The experimental animals developed
      hydrothorax and pulmonary oedema, and died in 5-6 days. The clinical symptoms and
      pathological lesions were consistent with those of porcine pulmonary oedema (PPE)
      diagnosed in the USA in 1989-1990, as well as with those of a disease entity that
      had already been described in Hungary in the 1950s as the so-called fattening or
      unique pulmonary oedema of pigs but considered to be of unknown aetiology. The
      results of the feeding trial confirm that this pig disease, which has occurred in
      Hungary for a long time, is caused by the mycotoxin fumonisin B1.

PMID- 9588113
TI  - Reproducibility of antibiogram of bovine mammary gland staphylococci under
      conditions of repeated subculturing.
AB  - The reproducibility of antibiogram profiles of 10 staphylococcal isolates of
      bovine mammary gland origin was tested under conditions of repeated subculturing.
      Prototype (original or index) antibiogram profiles were determined by
      subculturing these isolates from stock cultures stored at -70 degrees C. The
      isolates were then subcultured four times on blood agar and antibiogram profiles
      determined at each subculture on Mueller-Hinton agar. The antibiogram profiles of
      each isolate at each subculture were compared with the prototype profiles of that
      isolate. At repeat antibiogram determinations, deviations of < or = 5 mm in the
      individual zones of inhibition of penicillin, ampicillin and streptomycin from
      the prototype antibiogram profiles, resulted in a shift of only three isolates
      from the resistant to intermediate and one isolate from intermediate to resistant
      status of antibiotic susceptibility classification. It is suggested that in the
      interpretation of antibiogram, susceptibility classification (resistant,
      intermediate, or susceptible) variations accruing from a few millimetres
      differences in the diameter of the zones of inhibition should probably be
      disregarded.

PMID- 9588114
TI  - Galvanic cultures: electricity and life in the early nineteenth century.
AB  - Electricity has long proved to be a powerful tool for investigating the
      properties of life. Towards the beginning of the nineteenth century new
      discoveries and inventions in electricity stimulated a new popular fascination
      with such questions. Electricity seemed a good way of understanding the machinery
      of life. It was the key to unlocking the secrets of vitality. Looking at these
      early nineteenth-century debates and discussions provides a good way of focusing
      on the cultural connections and ramifications of science. As electricity provided
      tools for understanding life, it provided tools for understanding culture also.

PMID- 9588115
TI  - Twisting the ladder of science: pure and practical goals in twentieth-century
      studies of inheritance.
AB  - In the twentieth century studies of inheritance have been driven by both
      practical and theoretical concerns. The metaphor of a ladder helps to illustrate
      how applied and pure interests have worked together in scientific development.
      This 'ladder' has significant 'twists' in it due to the unique nature of
      genetics, entwining the science of heredity with powerful and possibly
      compromising personal, social and commercial agendas. These implications are
      manifest in the history of agricultural research, eugenics, and the business of
      science. Today, as in the past, genetics is a prestigious science that requires
      cautious movement forward as human beings face its tremendous challenges and
      potential dangers.

PMID- 9588116
TI  - Second thoughts on psychedelic drugs.
AB  - Psychedelic drugs are making a comeback. Proponents of psychedelics point to the
      widespread medical experimentation with mescaline and lysergic acid diethylamide
      125 (LSD) in the 1950s as proof of their safety and efficacy. However, a review
      of the private and published writings of Sidney Cohen, MD, who conducted the
      first study of the safety of psychedelics, reveals that serious medical concerns
      about psychedelics arose before the public backlash against the drugs in the
      1960s. The story of psychedelic research is a reminder of the inevitable
      complications involved in testing drugs on human subjects.

PMID- 9588117
TI  - Prepubertal periodontitis: a genetic analysis.
AB  - Genetic factors were recognized as possible predisposing factors in the
      etiopathogenesis of prepubertal periodontitis (PP). Consequently, the present
      work was carried out to determine the possible mode of inheritance and if there
      were any associated chromosomal aberrations in cases with PP. The study included
      3 families with probands manifesting PP (the families included 18 individuals).
      Pedigree analysis was carried out as well as chromosomal analysis. The results
      pointed out to the possibility of new mutations arising due to various
      environmental factors (including the use of pesticides and their handling), in
      addition to a possible autosomal recessive inheritance. Chromosomal analysis
      showed no association between a certain chromosomal aberration and PP. An
      interesting finding was that a girl proband proved to be Xo female, i.e. a case
      of Turner's syndrome. This could be considered the first report of Turner's
      syndrome with PP.

PMID- 9588118
TI  - The incidence of Streptococcus pyogenes in throat and plaque cultures in cases
      with acute throat infections.
AB  - This study was performed on 50 children with clinically suspected streptococcal
      upper respiratory tract infection at Abu-El-Rich hospital. DMF and plaque indices
      were recorded for all cases. Plaque and throat swabs were taken from all patients
      and directly inoculated on sheep blood agar plates. Haemolytic streptococci were
      further identified presumptively using bacitracin. 34% of cases had Beta
      haemolytic streptococci type A (streptococcus pyogenes) in throat and 8% of cases
      had the same bacteria in plaque as well. This emphasizes the importance of proper
      plaque control in children together with the prophylactic ten days of antibiotic
      treatment in cases with acute throat infection to avoid the development of
      rheumatic heart disease in children.

PMID- 9588120
TI  - Evaluation of the porcelain laminate veneers as a new esthetic and reconstructive
      modality.
AB  - Veneers are being used for the esthetic improvement of anterior teeth, and
      porcelain veneers are a recent development in this field. This article will
      described briefly the porcelain laminate technique and attempts to evaluate it as
      a new esthetic and treatment modality. Though there are some shortcomings yet the
      advantages afforded by this system are considerable enough to make the technique
      deserving of further investigation.

PMID- 9588119
TI  - Dental, oral and bacteriological aspects in patients at risk of subacute
      bacterial endocarditis.
AB  - The present investigation was performed on 100 patients, at the Cardiac Institute
      in Imbaba suffering from either rheumatic heart disease or congenital heart
      disease. In all the patients, the cardiac, dental and periodontal conditions as
      well as any other oral manifestations were evaluated. Bacterial samples of plaque
      and throat were taken in cases receiving long-acting penicillin. In most of the
      cases, the caries, plaque and periodontal indices were very high and in cases of
      congenital heart disease, there was atrophy of the tongue coating. The bacterial
      ecology of dental plaque changed in most of the patients taking long-acting
      penicillins with supervening Streptococcus viridans, E. coli and Staphylococcus
      aureus. The results stress on the importance of proper antibiotic prophylaxis
      before any dental intervention as well as through oral hygiene procedures.

PMID- 9588121
TI  - The predictive value of circulating immune complexes (CIC) in patients with
      malignant salivary gland tumors.
AB  - The present study included nine patients suffering from various types of
      malignant salivary gland neoplasms. The patients were monitored both pre and post
      operatively utilizing the circulating immune complex assay. The (CIC) levels
      decreased significantly after the surgical eradication of the neoplasms. This
      diagnostic parameter proved to be of great value in monitoring therapy in
      patients with various types of malignancies.

PMID- 9588122
TI  - The effect of calcium overdosages on the rate of eruption and periodontal
      ligament of lower incisor in albino rats.
AB  - The study was conducted to determine the effect of calcium overdosages on the
      rate of eruption of lower incisor in albino rats. The experiment was carried out
      on a group of rats, and calcium was supplemented to the experimental animals in a
      dose of 450 mgm CaCl2/100 gm diet. The lower right incisor in control and
      experimental rats was transected out to the level of gingival margin and then the
      emerged portion of the growing tooth was measured twice weekly for the
      determination of eruption rate. The periodontal ligament of the tooth was
      examined to detect any histological change. The results indicated acceleration in
      rate of eruption of the tooth secondary to calcium administration, increase in
      thickness and vascular supply of its periodontal ligament and increase in the
      height of inner enamel epithelial cells and cellularity of enamel organ at the
      base of the root.

PMID- 9588123
TI  - A clinical and histological comparative study of the effect of nifedipine and
      phenytion on human gingiva.
AB  - Ten patients manifesting gingival enlargement were chosen for this study. Five
      patients had been treated with 4 mg nifedipine per day as a treatment for angina
      pectoris, while the other five patients treated with phenytion as an
      anticonvulsant drug. Clinical and histological data showed that nefidipine
      induced gingival hyperplasia which is of close similarity to that induced by
      phenytion despite the differences in target tissue.

PMID- 9588124
TI  - Biological influence of some crown and bridge restorative materials finished and
      polished by different techniques.
AB  - Fixed restorations should satisfy certain biologic requirements and they must not
      be injurious to the surrounding living tissues as pulp, periodontal ligament,
      alveolar bone and gingiva. It is best to terminate preparations above the
      gingival margin but for retention and esthetics considerations the margins of the
      fixed restorations could be placed subgingivally. In recent years, the biologic
      effects of dental restorative materials on the gingiva and periodontal tissues
      have been better appreciated. A rough surface restoration attracts and retains
      bacterial plaque and irritates the surrounding soft tissues which is injurious to
      the living supporting structure of the abutments.

PMID- 9588125
TI  - Resistance to fracture of high-strength porcelain crowns versus metal ceramic
      crowns under different conditions.
AB  - Although the good appearance and biocompatibility of dental porcelains, failures
      are still of considerable concern because of the limited properties to all
      ceramic system. Physical properties that might be considered ideal include high
      strength, resistance to abrasion, and resistance to the hostile oral environment.
      Porcelain has been considered by many of its physical characteristic are similar
      to those of enamel. In 1983 a new modality of treatment, the etched porcelain
      restoration was introduced by Simonsen and Calamia. Numerous investigations have
      shown the strength of the etched porcelain bonded to composite resin and also the
      clinical success of this porcelain to be used as laminated veneers and etched
      inlays and onlays.

PMID- 9588126
TI  - A study of infraorbital foramen, canal and nerve in adult Egyptians.
AB  - The infraorbital foramen, canal and nerve were examined in 30 Egyptian adult
      skulls and 15 adult human cadavers. The infraorbital foramen was single in 90% of
      cases and double in 10%. It was oval in 65% of cases and round in the remaining
      cases. It was directed downward, forward and medially in 60%, downward in 25% and
      medially in 15% of cases. The distance from the centre of the foramen to the
      inferior orbital margin was 6.1 +/- 2.4 mm and to the lateral nasal border was
      14.7 +/- 2.7 mm. The infraorbital foramen was opposite the 2nd maxillary premolar
      in 50% of cases, opposite the 1st premolar in 15% and between the 1st and 2nd
      premolar teeth in 15% of cases. The length of the infraorbital canal was 28.8 +/-
      2.9 mm and it showed an infraorbital groove in 60% of cases, a complete roof in
      25% and a deficient roof leaving a short bony bridge in 15% of cases. The
      anterior superior alveolar nerve arose either from the middle third of the
      infraorbital nerve (in 10 out of 15 cases) or from its anterior third in the
      remaining 5 cases. The middle superior alveolar nerve was not apparent in 8 cases
      and it arose from the middle third of the infraorbital nerve in the remaining 7
      cases. Radiographic study of the infraorbital foramen and canal on 15 adult dry
      skulls were also done using 3 different views for each skull. The panoramic view
      showed to be better than either of the lateral or the postero/anterior view.

PMID- 9588127
TI  - Clinical evaluation of pulsed ND:YAG dental laser applied on oral soft tissues.
AB  - This investigation was conducted to evaluate the pulsed Nd: YAG dental laser, as
      a surgical tool for many of the oral surgical procedures. Gingivoplasty, minor
      gingivectomy, operculectomy excision of pedunculated tumors, frenectomy, incision
      and drainage of oral abscesses, control of oral bleeding and many other
      procedures were included in the study. The results presented here suggest that
      the pulsed Nd: YAG laser can be used to cut efficiently through vascular tissues,
      necrotic tissues and thin pedunculated masses. So it could be considered
      selective but not conclusive in surgery of the oral soft tissues.

PMID- 9588128
TI  - Effect of surface treatments and storage methods on the shear bond strength
      between composite/glass-ionomer cement laminate.
AB  - The shear bond strengths between a visible light cure posterior composite and
      different surface treatments of glass-ionomer Cement were estimated in the dry
      and wet conditions. A total number of 60 specimens were used in the present
      investigation. The specimens were divided into 6 equal groups (10 specimens
      each). Each group was divided into two equal subgroups, in order to study the
      effect of the storage condition on the shear bond strength for each group. It was
      found that group (V), where saline coupling agent was applied to the non-etched
      glass-ionomer cement surface, followed by the application of bonding agent,
      demonstrated the maximum shear bond strength (10.87 mm/m2). On the other hand,
      group (II) where composite resin was packed directly on the etched glass-ionomer
      surface displayed the minimum shear bond (1.93 Mn/M2). Moreover, the wet storage
      of the different groups elicited a varying percentage of reduction in the shear
      bond strength values.

PMID- 9588129
TI  - Effect of different post-cure heat-treatment methods on the dimensional stability
      of a visible-light cured-composite inlays.
AB  - A total number of 50 rectangular specimens, made of hybrid visible light cured
      composite were used in the present study. The specimens were divided into 5
      groups (10 specimens each). Each group was treated with one of the post-cure heat
      treatment methods. It was found that, the specimens exposed to the normal post
      cure heat-treatment method demonstrated the minimum dimensional change values
      (0.62%, 0.166%, 1.4% and 2.23%) for length, width, and volume respectively. On
      the other hand, the specimens exposed to the (delay-heat) water ageing method
      displayed the maximum values (2.9%, 0.56%, 9.2%, and 9.98%) for the length,
      width, height, and volume respectively.

PMID- 9588130
TI  - Surgical correction of recurrent stenosed submandibular duct orifice.
AB  - Ten patients complaining of recurrent stone formation in submandibular stenosed
      duct orifice were diagnosed and evaluated. Surgical technique for removal of the
      stones and widening of the orifice to heal by secondary intention was discussed.
      Irrigation of the duct and wound with 5% diluted hydrogen peroxide was done to
      remove all desquamated epithelial cells and microliths to prevent narrowing the
      lumen of the duct. One year post operative follow up revealed no recurrence of
      stone formation in the submandibular duct and normal salivary flow for all
      patients.

PMID- 9588131
TI  - Ruffle-ended maturation ameloblasts in the pigmentation zone of rat incisor.
AB  - Rats were perfused with glutaraldehyde and the incisors were dissected free.
      Midsagittal slice of the incisor were demineralized and the pigmented zone were
      further sliced into thin cross sections. The lysosomal activity was demonstrated
      utilizing CMPase. Two patterns of localization were observed. Weak local reaction
      product associated with the pigment granules. The second one was intense reaction
      product with some of the ruffled border of ameloblasts. A suggested role for
      these localizations were discussed in relation to pigment release into the enamel
      surface.

PMID- 9588132
TI  - Effect of laser enamel-etching on the bond strength of resin-bonded retainers.
AB  - In this study, thirty extracted maxillary incisors of comparable sizes were used.
      The teeth were prepared to receive resin-bonded retainers. Each retainer was
      constructed with a ring on the palatal surface for bond strength testing. The
      specimens were divided into two groups. The enamel of the palatal surface of each
      tooth in the first group was etched using the acid gel etching technique. Laser
      etching was used in the second group. The etched cast metal retainers of both
      groups were bonded to the corresponding etched teeth using Nimetic-Grip luting
      composite. The bonding strength was tested using Instron Testing Machine. From
      this study, the following conclusions were reached: 1. The results of this study
      proved that, laser was a successful tool for etching of the enamel surfaces. 2.
      Comparable results of laser etching and acid etching of the enamel were obtained,
      as they both gave a satisfactory bond strength to the resin-bonded retainers.

PMID- 9588133
TI  - Finishing of glass-ionomer cement (SEM study).
AB  - A total of 12 glass-ionomer cement specimens were utilized in the present study.
      The specimens were divided into two equal groups. The first group was used after
      10 minutes from setting, while the second was utilized after 24 hours from
      setting. Each group was divided into three equal subgroups (2 specimens each).
      The first subgroups were finished under wet condition (wet finished). The second
      subgroups were dry finished. On the other hand, the third subgroups were kept
      undisturbed (as set) under mylar strips. The specimens surfaces were then
      examined by a Scanning Electron Microscope (SEM). It was found that, finishing of
      the specimens after 24 hours from setting demonstrated more acceptable surface
      topography either in wet or dry conditions than finishing after 10 minutes from
      setting. Moreover, the dry finished specimens displayed more acceptable surface
      topography than the wet finished specimens. On the other hand, the as set
      (undisturbed) specimens the most acceptable surface topography.

PMID- 9588134
TI  - Role of fluoride on corrodability of dental amalgams.
AB  - The role of fluoride ions on the corrosion behavior of some commercial dental
      amalgam in artificial saliva solution at pH level 7.1 was studied by using
      impedance and potentiodynamic polarization techniques. It was found that, the
      presence of F- ions in an artificial saliva solution at pH 7.1 increases the
      corrodability of different types of dental amalgam. Sever pitting corrosion
      occurred at level of 100 mM F- ions. The formulation of amalgam alloys greatly
      affect the resistance to pitting corrosion; the resistance of the amalgam to
      pitting follows the order: Dispersalloy >> Phasealloy > Oralloy > Tytin > Valiant
      pH.D. It is recommended to avoid oral treatment involving high F- ions
      concentration in the presence of amalgam restorations.

PMID- 9588135
TI  - The use of precision attachments in a lower full arch rehabilitation with
      osseointegrated implants--a clinical report.
AB  - A technique for restoration of a case of Kennedy Class V edentulous span was
      described. This situation is a long edentulous span bounded anteriorly by a weak
      support and considered as one of the most difficult situations to restore. Two
      osseointegrated screw implants were inserted in the edentulous span. Together
      with remaining natural teeth supported a full arch restorations. Three precision
      attachments were included in the restoration to allow movement of the remaining
      teeth and to allow broken stresses at where the prosthesis extended along the
      corners of the mouth.

PMID- 9588136
TI  - Prevention of tooth hypersensitivity caused by the hydrodynamic action of zinc
      phosphate and composite resin luting cements (SEM) study.
AB  - This study was done to determine the role of cement liner as a reducing factor to
      the fluid movement in order to prevent tooth hypersensitivity according to the
      hydrodynamic theory during cementation of crowns. A total of fourty freshly
      extracted intact lower molar were selected for this study. After conventional
      tooth preparation the teeth were sub-divided into four equal groups to identify
      the role of cement liner in preventing the penetration of used cement into the
      dentinal tubules. Scanning electron microscopic study proved the efficiency of
      glass ionomer liner on preventing cement penetration into the dentinal tubules.

PMID- 9588137
TI  - Long-term follow-up of glutaraldehyde pulpotomies in young permanent molars.
AB  - Fifteen children with fifteen cariously exposed first permanent molars were
      treated with glutaraldehyde pulpotomies, using 5 percent buffered glutaraldehyde
      (pH8). All cases were followed up for a five-year period. Clinical and
      radiographic success rates obtained at the end of the fifth year were 93.3%.

PMID- 9588138
TI  - A comparative electrochemical study of corrosion susceptibility of some Pd
      enriched amalgams.
AB  - Cyclic polarization technique was used to determine the corrosion susceptibility
      of some Pd-enriched amalgams as compared with the conventional and high-copper
      ones. Different oxidation and reduction peaks and their corresponding current
      intensities were determined in each case. Corrosion indices I and II were also
      calculated. Pd-enriched amalgams have shown lower corrosion susceptibility than
      conventional or unicompositional high-copper amalgams. A role was attributed to
      the alloy composition and the relative cathodic (reduction) current available.

PMID- 9588139
TI  - Bonding of laminate veneer materials to enamel.
AB  - The purpose of this study is to examine the effect of enamel surface pretreatment
      on the shear bond strength of tooth colored restorative materials bonded to human
      enamel with different luting systems. Forty-two extracted human molars were used
      in this study. Buttons, 6 x 3 mm., of two types of composite resin (Silux# &
      Visio-Gem@) and 5 x 3 mm. buttons of dental porcelain, were prepared. The
      prepared buttons were attached to the buccal, lingual and proximal surfaces of
      extracted molars. The enamel surfaces were cut in some groups while left uncut in
      other groups. One, or a combination of two, of the following luting materials was
      used with the composite resin groups: Chemically-cured Scotchbond#; Light-cured
      Scotchbond#; Visio-Gem; Visio-Gem Glaze@ and Conclude@. For the porcelain groups,
      Scotchprime#, Conclude, Silux, and Visio-Gem were used as luting materials.
      Samples were tested on an Instron testing machine. Single factor analysis of
      variance of the data obtained that: a) In the Silux groups there is no
      significant difference in shear bond strength between cut and uncut enamel with
      different luting systems; b) Among the Visio-Gem groups the highest shear bond
      strength is obtained with the cut enamel surface when a combination of Visio-Gem
      and Visio-Gem Glaze was used as luting material; c) The porcelain groups show the
      highest shear bond strength with the enamel surfaces trimmed flat and the use of
      a combination of Scotchprime and Conclude as luting material.

PMID- 9588140
TI  - Immunopathology of T-lymphocyte subsets in juvenile and rapidly progressive
      periodontitis.
AB  - The immunopathology of T4 & T8 cell subsets in gingival tissues from 20 patients
      affected with either juvenile (JP) or rapidly progressive periodontitis (RPP)
      were studied using immunoperoxidase method for monoclonal antibodies of T4 & T8.
      Results were compared with gingival samples taken from systemically and
      periodontally healthy subjects. T4 subsets were found to be significantly
      elevated in JP & RPP, when compared with controls. Yet it was found to be higher
      in JP than in RPP, while T8 subsets were found to be depressed in both types of
      diseases. Those findings could contribute to the immunopathogenesis of JP & RPP.

PMID- 9588142
TI  - Microleakage of computer-generated Vita Cerec and Vitadur-N laminate veneers.
AB  - Laminate veneers are now used as conservative aesthetic alternatives to full
      coverage restorations in some cases, especially in young adults and children.
      With the development of improved restorative resin systems and the acid etch
      technique, thin preformed plastic laminate veneers were bonded to the labial
      surfaces of discolored, developmentally deformed or fractured teeth. However,
      aesthetic failure due to color instability, staining and wear happened. Now, with
      bonded porcelain veneers it is possible to achieve both an aesthetic result and a
      veneer preparation while restoring the function of anterior teeth. They are also
      used to restore fractured incisors. Ceramic veneers hold advantages over
      composite resin veneers in color stability, were resistance and lifelike
      aesthetics.

PMID- 9588141
TI  - A retrospective study on the relationship between miswak chewing stick and
      periodontal health.
AB  - Chewing sticks have been used for centuries as a tooth cleaning device. One of
      the most commonly used types is known as the miswak. Despite its wide use, few
      studies have examined its effects on the gingival health. The purpose of this
      study is to examine the relationship between miswak and gingival health in terms
      of pocket depths, periodontal disease severity and gingival recession. The
      incisors, canines and premolars were examined in a total of 264 patients who were
      seen for routine periodontal treatment. Information regarding the use of the
      miswak, oral hygiene habits, as well as clinical measurements of pocket depth,
      periodontal disease and gingival recession were obtained from patients charts.
      Patients were divided into two groups: a miswak group and a Toothbrush group. The
      results of this study indicated that the use of miswak may influence periodontal
      health and may be considered as a factor contributing to gingival recession. It
      is suggested that additional research is needed to examine the relationship
      between miswak and periodontal health.

PMID- 9588143
TI  - Natal and neonatal teeth.
AB  - The purpose of this report is to present two cases of natal and neonatal teeth
      including discussion on the various features concerning these conditions as well
      as the possible management strategies. The first case is a natal tooth in a
      newborn Saudi girl while the second case is two neonatal teeth in a Saudi boy.

PMID- 9588144
TI  - Bleaching of discolored teeth.
AB  - Bleaching is a viable treatment alternative to attempt esthetic improvement of
      discolored teeth. Natural tooth structure as opposed to a veneer or crown margin
      is considerably superior in tissue response. Caution has to be exercised in
      selecting cases and advising patients of the possibilities from bleaching and
      that bleaching may not be entirely successful or lasting. It still should be
      considered as a treatment of first choice. If applied properly and in carefully
      selected cases the results can be very rewarding for the dentist and especially
      the patient. A knowledge of the agents used and biological limits must be kept in
      mind when bleaching teeth to prevent potential disastrous complications. It is
      especially important to keep the bleaching time to the shortest effective time
      possible with vital pulps. Bleaching when successful provides a superior margin
      and a less expensive alternative than crowns. Bleaching should generally be
      considered before crown preparation because if bleaching is unsuccessful crowns
      can always be fabricated. This is true for younger individuals with tetracycline
      stained teeth because crowns may need to be remade several years after their
      initial placement due to further eruption of teeth and further recession of the
      gingival tissues.

PMID- 9588145
TI  - Distribution of keratin polypeptides in adult, juvenile and rapidly progressive
      periodontitis.
AB  - Inflammation of human gingival tissues including the periodontal structures
      occurs in response to infection in crevicular sulcus caused by microorganisms
      which first attach to the surface of oral squamous epithelium, penetrate into
      inner gingival epithelium and finally through the basement membrane of the
      underlying connective tissue (Murase et al., 1985). Other authors have long held
      the view that periodontitis is not a homogeneous disease entity but rather a
      group of family related diseases manifesting similar features and different
      etiologic factors. Immunological mechanism have long been implicated in
      pathogenesis of chronic periodontitis. Defect of host mechanism may have a
      relationship in development of rapidly progressive periodontitis (RPP) (Page et
      al., 1983).

PMID- 9588147
TI  - Hypodontia of primary and permanent teeth in a sample of Saudi children.
AB  - Hypodontia, congenitally missing teeth is more common in permanent than primary
      dentition. The present investigation reports the prevalence and pattern of
      hypodontia in the primary and permanent dentitions, excluding third molars in a
      sample of Saudi children. The sample consists of 1,300 children, aged 5 to 10
      years of age. Clinical and radiographic examinations were performed. The
      prevalence of children with hypodontia was found to be 2.6 percent. The
      mandibular second premolar was the tooth most frequently absent and account for
      45 percent of the total missing teeth. In primary dentition, the maxillary
      lateral incisor was the tooth most frequently absent (9%). A peg-shaped permanent
      maxillary lateral incisor was present in 0.7 percent of the sample. Congenitally
      missing teeth were almost equally distributed between maxillary (52%) and
      mandibular (48%) arches.

PMID- 9588146
TI  - Microleakage of oral microflora for porcelain and some porcelain repair materials
      -in vitro study.
AB  - Repairing porcelain fractures has become of interest to the dentist. The intra
      oral fracture of metal-ceramic restorations may be due to inadequate metal
      support, excessive porcelain thickness, technical flaws, and occlusal forces.
      Various techniques for intra oral porcelain repair have been suggested. The resin
      porcelain junction has been in question since the advent of the porcelain veneer
      for cast metal restorations. To enhance this, several intermediary products and
      techniques have been developed to increase the chemical bond between the
      fractured porcelain and the repair materials. Clinical procedures for porcelain
      repair has required roughening of porcelain surface with a rotary abrasives,
      application of silane followed by composite to replace the contour of the
      restoration (2, 13, 14). Laboratory data suggested that the strong bond of the
      repair materials was developed.

PMID- 9588148
TI  - Demonstration of T-cell subsets in oral lichen planus.
AB  - The distribution of "T" cell subsets (T4 & T8) in 10 lesions of oral lichen
      planus was investigated using an immuno-peroxidase technique. Most of the
      infiltrating cells consisted of a mixture of T4 (helper/inducer) and T8
      (suppressor/cytotoxic) cells, presented in the stroma with varied intensity in
      their distribution. The present study proved that emigration of lymphocytes,
      through subepithelial vessels, was not selective for the major subsets of T
      cells. Subsequent migration of T8 toward the epithelium was predominant. The
      present study also support the view that T8 may have a role in the local
      destruction of the basement membrane. The immuno-regulatory status between T4 &
      T8 may be responsible for the different clinical forms of lichen-planus.

PMID- 9588149
TI  - Assessment of three different methods of tissue dilation for ceramometal
      restoration.
AB  - Tissue dilation is one of the key factors in obtaining accurate duplication of
      subgingival finishing lines and hence excellent marginal adaptation of the
      restoration. Elastic impression materials do not displace the tissue. Therefore,
      the tissue must be displaced away from the prepared teeth or a small ribbon of
      the free gingiva must be removed to expose the finishing line before making the
      impression.

PMID- 9588150
TI  - Marginal castability of two different materials (a comparative study).
AB  - Achieving a clinically acceptable margin is a conspicuous objective to any
      practicing dentist. The main concern is the space existing between the margin of
      the prepared tooth and that of the final restoration. Marginal fit has been
      measured and evaluated in a variety of methods., and a gap of approximately 50
      microns is usually considered acceptable. While inlay wax is the material
      commonly used in the wax-up stage when fabricating crowns and bridges, Duralay
      (methylmethacrylate) is a material widely used nowadays in the field of fixed
      prosthodontics. Due to the ease of using this material intra-orally to form
      margins, an attempt is made to compare the castability of margins made out of
      inlay wax to the ones made out of Duralay.

PMID- 9588152
TI  - Critical appraisal of magnetic resonance imaging (MRI) in internal derangement of
      temporomandibular joint.

PMID- 9588151
TI  - Identification of lymphocyte subsets in pregnancy gingivitis.
AB  - The percentage of gingival tissue and peripheral T, T Subsets and B lymphocytes
      were assessed in ten pregnant women during the first, second and third
      trimesters. Clinically the gingival index (GI) was found to be higher during
      pregnancy than in the control group. The percentage of the T3, T4 and B cells
      appeared to decrease in peripheral blood and gingival tissues during pregnancy as
      compared to control group.

PMID- 9588153
TI  - Fracture resistance in conservative Class II cavity preparation: box vs tunnel.
AB  - A total of 40 extracted human maxillary premolar teeth were used in this study.
      Teeth were randomly distributed between two main groups. In group A conservative
      class II Box preparations were cut in each tooth. In group B the proximal cavity
      was prepared through the occlusal surface and the proximal marginal ridge was
      left intact (tunnel preparation). Group A and group B were randomly subdivided
      into two subgroups (a & b). In groups Aa and Bb a posterior composite resin
      material was used to restore the prepared cavities (no base was used). While in
      groups Aa & Bb the posterior composite resin was used with a glass ionomer cement
      base. The teeth were tested on an Instron testing machine for their resistance to
      fracture, force being applied equally to buccal and lingual cusps. Mean fractures
      values were: Gp. Aa 285 LB.: Gr. Bb 245 lb. Bb 240 lb. One way analysis of
      variance showed no statistical difference between the four groups. The tunnel
      preparation did not increase the resistance to fracture of the restored tooth
      compared to a box preparation.

PMID- 9588154
TI  - The effect of fluoride treatments on glazed and polished ceramic surfaces.
AB  - A scanning electron microscope (SEM) Study was conducted to evaluate the
      micromorphology of glazed and polished ceramic restoration surfaces after
      treatment with different types of fluorides with different concentrations and
      acidity. This study showed that glazed ceramic surfaces appeared to be smoother
      and more resistant to fluoride agents than polished ceramic surfaces. Fluoride
      agents with a lower pH (more acidic) and higher in fluoride concentration caused
      more surface damage to porcelain. Therefore, it is recommended to use a neutral
      fluoride agent with low fluoride concentration. If the ceramic restoration is to
      be polished after glazing due to clinical adjustment, it is advisable to reglaze
      it particularly before fluoride application.

PMID- 9588155
TI  - Influence of water exposure on leakage of fillers and topography of composite
      resin restoratives.
AB  - Double-beam atomic absorption spectrophotometer was used to study the leakage of
      fillers from six brands of commercial composite resin restoratives, after 40 and
      80 days of water immersion. In addition SEM was used to study the topographic
      changes of the immersed restoratives after the second test period. The results
      indicated that fillers as Si, B, Sr, Ba, Sb, Mg and Al leaked out in considerable
      amounts after the two immersion periods. SEM study revealed deteriorated picture
      of the restoratives characterised by fillers degradation, crack propagation and
      debonding. The authors believed that hydrolytic degradation of the fillers of
      composites was a great failure mechanism.

PMID- 9588156
TI  - Effect of inhibitory species on electrochemical corrosion of high copper amalgam.
AB  - This investigation evaluates the corrosion potential of high copper amalgam
      containing inhibitory species, sodium phosphate and sodium citrate, in artificial
      saliva at different pH levels. The data revealed that the phosphate incorporated
      in high copper amalgam leads to increase in passivation of the alloy as compared
      to less or even negative effect of citrate incorporation. The linear steady
      potential of the amalgam was closer to the reversible potentials corresponding to
      hydrogen evolution and tin oxide formation. The corrosion potential does not
      respond reversibly to pH of the saliva solution due to the pronounced passivation
      of the high pH levels.

PMID- 9588158
TI  - Luminal epithelium of Warthin's tumours: a scanning electron microscopic study.
AB  - Three cases of papillary cystadenoma lymphomatosum were examined by light and
      scanning electron microscope to declare the morphology of the luminal epithelial
      surface. It was found that ciliated cells were present in one case. This finding
      explains the origin of ciliated cells as a development included in the
      neighbouring lymph node with a tendency of metaplastic change and exfoliation.

PMID- 9588157
TI  - Effect of addition antimicrobial agents to denture reliners.
AB  - This study aimed at evaluating the incorporation of two antimicrobial drugs
      (nystatin and polynoxylin) as regards: the effect of the liner on the activity of
      the drug, determination of the least effective concentration of each drug and its
      duration of action, as well as assessment of the effect of the drug on the
      mechanical properties and the chemical composition of the liner. Results showed
      that nystatin added to denture liners in three different concentrations by weight
      (3%, 5%, 10%) acted effectively against Candida albicans, and that there was a
      direct relationship between concentration of Nystatin and its duration of action.
      The inhibitory effect of nystatin (10%) lasted for at least 32 weeks (end of
      study period). Furthermore, this concentration did not affect the strength
      properties of the liner. On the other hand, polynoxylin inhibited a number of
      strains of bacteria and Candida only in high concentrations (40-60%), and these
      concentrations adversely affected the strength properties of the liner.

PMID- 9588159
TI  - Variations in nucleolar organizer regions during 9-10 dimethyl1-2 benzanthracene
      induced tongue carcinogenesis in rats.
AB  - The quantitative and qualitative changes of transcriptionally active nucleolar
      organizer regions (NORs) identified by silver staining (AgNORs) were observed in
      rat tongue lesions induced by 9-10 dimethyl 1-2 benzanthracene (DMBA). Epithelial
      hyperplasia, mild, moderate dysplasia and severe dysplasia (with or without
      invasive squamous cell carcinoma) were induced 4,6,8 & 10 weeks respectively
      after implantation of 5 mg DMBA in the submucosa of rat's tongues. A general
      trend towards an increase in the mean AgNOR counts with longer time and resultant
      histopathological findings was observed, where the lowest value (2.44 +/- 1.00)
      was found in specimens showing epithelial hyperplasia (4 weeks after DMBA
      implantation) and the highest value in those showing severe dysplasia with
      invasive squamous cell carcinoma (10 weeks after DMBA implantation). Clumping and
      irregularity of AgNOR dots were demonstrated in DMBA treated specimens and were
      found to increase with higher degrees of epithelia dysplasia. The dispersal of
      the AgNOR dots in the nucleoplasm indicating high cellular activity was
      characteristically evident in specimens showing severe dysplasia with invasive
      squamous cell carcinoma. Our results suggest that although AgNORs can be useful
      as a qualitative marker of cellular activity at the early stages of DMBA tongue
      carcinogenesis, counting the AgNOR dots cannot be relied upon in discriminating
      the different degrees of induced cellular changes.

PMID- 9588160
TI  - Clinical survey of anterior and posterior ceramo-metal fixed partial dentures for
      middle-age group.

PMID- 9588162
TI  - An energy dispersive X-ray micro-analysis (EDX) interfacial study on a high
      copper amalgam/polycarboxylate cement combination.
AB  - The interface between a polycarboxylate cement and a high copper amalgam core
      containing (21%) tin by weight was analyzed by EDX. It was found that, the tin
      concentration at the interface was very low (1.26%). On the other hand, a higher
      copper concentration was demonstrated (6.39%). Mean while a correlation was
      established between the tin concentration of the amalgam core and the shear bond
      strength with polycarboxylate cement. Moreover, it could be assumed that, the tin
      concentration rather than the copper concentration of the amalgam cores has the
      substantial effect on the shear bond strength between amalgam cores and
      polycarboxylate cement.

PMID- 9588161
TI  - Effect of fluoride application on specular reflectance and stain potential of
      unfilled and photocured microfilled resin veneering materials.
AB  - A laboratory study was conducted to determine the effect of application of four
      types of fluoride solutions commonly used and administered by dentists on the
      specular reflectance and staining potential of photocured and regular unfilled
      resin veneering materials. The fluoride solutions used were: (1) 1.23% acidulated
      phosphate fluoride gel (APF) gel, (2) 0.4% stannous fluoride gel, (3) 0.2% sodium
      fluoride solution and (4) .05% sodium fluoride solution. Specular and diffuse
      reflectance using scanning spectrophotometer were carried out for the fluoride
      treated samples and the control untreated samples before and after staining. The
      results revealed that the (APF) gel, produced the highest surface roughness and
      staining ability followed by the stannous fluoride solution for the both tested
      veneering materials. The sodium fluoride mouth wash solutions (0.2% and 0.05%)
      produced the least effect. So, on the bases of these results, caution should be
      taken in utilization of fluoride treatment in patients with prosthesis containing
      resin veneering material.

PMID- 9588163
TI  - Short- and long-term effects of thumb-sucking habit breaking appliance on speech
      in children.
AB  - Fourteen children with thumb-sucking habit breaking appliances were evaluated for
      any defective speech. They were tested before insertion, 3 months, and 6 months
      after appliance placement. Also, after 6 months from appliance removal to test
      the short- and long-term effects on speech respectively. The results revealed
      that the habit breaker caused short-term deleterious effects on speech but no
      long-term effects after removal of the appliance. This appliance should only be
      used with children older than 4.5 years whose speech is mostly developed. While
      wearing the appliance, speech will be improved over time on individual basis.

PMID- 9588164
TI  - Effect of application of ultrasonic vibrations on the cement bond strength of
      cemented cast crowns.

PMID- 9588165
TI  - Electrochemical microleakage assessment of three different root canal obturation
      techniques.
AB  - This study compared microleakage of lateral condensation, Thermafil and
      multiphase gutta-percha obturation technique using an electrochemical test
      system. The mean leakage current of three obturation techniques compared with
      that of positive samples. It was found that, the multiphase gutta-percha showed
      the least mean leakage current followed by Thermafil and lateral condensation
      techniques.

PMID- 9588166
TI  - Comparative sealability study on root canal obturation using multiphase gutta
      percha and lateral condensation technique.
AB  - An in-vitro dye leakage study was performed to compare the apical microleakage of
      recently introduced multiphase obturation system to lateral condensation
      technique using methylene blue dye. Thirty single rooted human teeth were divided
      randomly into two equal groups. Group A were filled with multiphase technique
      using Tubliseal sealer and group B were filled with lateral condensation
      technique using the same sealer (control). Root canal preparation of both groups
      were carried out with nickel titanium files. Statistical analysis revealed that
      multiphase technique exhibited lower mean leakage (0.6) than lateral condensation
      technique (1.72). In addition some specimen filled with multiphase technique
      showed zero degree leakage.

PMID- 9588167
TI  - Diagnostic imaging modalities in parotid gland enlargement.
AB  - Twenty patients with various parotid gland enlargement were selected from
      outpatient dental clinic. The classical sign of the parotid enlargement is
      swelling which may by localized as inflammatory, cystic, neoplastic or associated
      with systemic diseases as diabetes mellitus, sjogren's syndrome and may occur
      after ingestion of certain drugs or metals. These heterogeneous pathological
      swellings have great morphological variation that need various diagnostic imaging
      modalities to be visualized. The favoured modality has been evolved from plain
      radiography, to sialography, scintigraphy, ultrasonography and to computed
      tomography. The application and limitation of each modality were presented.

PMID- 9588168
TI  - The Rho small G protein family-Rho GDI system as a temporal and spatial
      determinant for cytoskeletal control.
AB  - Recent extensive studies have clarified the functions of the small G protein
      superfamily, which consists of the Ras, Rho, Rab, Arf, Sar1, and Ran families
      (for reviews, Refs, 1 and 2). The Ras family regulates gene expression at least
      through the MAP kinase cascade; the Rho family mainly regulates reorganization of
      the actin cytoskeleton; the Rab, Arf, and Sar1 families regulate intracellular
      vesicle trafficking; and the Ran family regulates nuclear transport. Of these
      cellular functions, reorganization of the actin cytoskeleton, seen in the
      formation of filopodia, lamellipodia, and ruffles during cell motility,
      dynamically occurs at specific sites of cells. To regulate this type of dynamic
      cellular functions, temporal and spatial determination mechanisms of signal
      transduction would be important. Like other G proteins, small G proteins cycle
      between the GDP-bound inactive and GTP-bound active forms (1,2). They receive
      upstream signals through their regulators and transduce signals to downstream
      targets while they stay in the GTP-bound form. Thus, G proteins serve as timers.
      There are at least three types of regulators for small G proteins: GDP/GTP
      exchange protein (GEP) which stimulates conversion from the GDP-bound form to the
      GTP-bound form; GDP dissociation inhibitor (GDI) which inhibits this reaction;
      and GTPase activating protein (GAP) which stimulates conversion from the GTP
      bound form to the GDP-bound form. Of these regulators, GDI has thus far been
      found for the Rho and Rab families. We have recently found that the Rho family
      Rho GDI system plays an important role in spatial determination in the actin
      cytoskeletal control (3-6). We briefly describe here this function of the Rho
      family-Rho GDI system.

PMID- 9588169
TI  - Cytochalasin D stimulation of tyrosine phosphorylation and phosphotyrosine
      associated kinase activity in vascular smooth muscle cells.
AB  - The actin filament-disrupting agent cytochalasin D strikingly increased tyrosine
      phosphorylation of a 75 kDa protein (p75) in rabbit aortic vascular smooth muscle
      cells. The microtubule-disrupting agent, colchicine had no effect on p75 tyrosine
      phosphorylation. Cytochalasin D also stimulated p75-directed kinase activity as
      determined by kinase assays of anti-Tyr(P) immunoprecipitates. Cytochalasin D
      stimulated tyrosine phosphorylation of the F-actin-binding protein, p80/85
      cortactin, but p75 was not immunologically related either to cortactin, the
      phosphatidylinositol 3'-kinase p85 alpha subunit, or the 80 kDa isoform of
      caldesmon. These results suggest that p75 may represent a cytochalasin D
      inducible kinase or kinase-associated component and provide evidence for the
      existence of a potentially novel kinase pathway regulated by disruption of the
      actin cytoskeleton.

PMID- 9588170
TI  - Genomic organization, promoter cloning, and chromosomal localization of the Dif-2
      gene.
AB  - We describe the genomic organization and the functional promoter of the monocyte
      specific gene Dif-2, the human homologue to genes in mouse (gly96) and rat
      (PRG1), that is downregulated during cell differentiation. The Dif-2 gene
      consists of two exons and a single intron of 112 bp in length. RNase protection
      assay indicates one major transcription start site. Sequence analysis reveals
      several consensus sequences for transcription factors including NF-kappa B,
      C/EBP, SP1, and the lack of a classical TATA-box. To demonstrate promoter
      activity, DNA fragments of the Dif-2 5'-flanking region were ligated upstream to
      the luciferase gene and transfected into HepG2 and HeLa cells. A minimal promoter
      element between nt -158 and nt +74 containing NF-kappa B and SP1 binding sites
      was shown to be sufficient for basal activity. These transcription factor binding
      sites, which are conserved between Dif-2, gly96, and PRG1 promoter regions,
      indicate a significant role for Dif-2 expression and may explain LPS and C2
      ceramide sensitivity. The Dif-2 gene was mapped to chromosome 6p21.3 using in
      situ hybridization technique.

PMID- 9588171
TI  - Two novel testicular serine proteases, TESP1 and TESP2, are present in the mouse
      sperm acrosome.
AB  - To identify a novel candidate(s) for acrosomal proteins that act on the sperm/egg
      interaction, a DNA fragment was PCR-amplified from a cDNA library of acrosin
      deficient mouse testis and then used as a probe to screen a mouse testis cDNA
      library. Complementary DNA clones encoding each of two similar but different
      serine proteases, TESP1 and TESP2, have been identified. The nucleotide sequences
      of these clones indicate that mouse TESP1 and TESP2 are initially synthesized as
      preproproteins of 367 and 366 amino acids, respectively. Comparison of the two
      TESP sequences with those of typical serine proteases suggests that each TESP
      zymogen is probably converted into a two-chain mature enzyme consisting of light
      and heavy chains covalently linked by a single pre-existing disulfide bond. The
      conversion may be accomplished by another protease(s) with a trypsin-like
      cleavage specificity, since it is unlikely that the mature TESP1 and TESP2 are
      capable of splitting the Lys-Ile bond between the light and heavy chains.
      Northern blot analysis of total cellular RNA demonstrates that the TESP1 and
      TESP2 genes are expressed only in the testis, and the transcripts are abundantly
      present in the haploid round spermatids. Moreover, immunocytochemical analysis of
      mouse cauda epididymal sperm using affinity-purified antibodies reveals that
      these two TESPs are both localized in the sperm acrosome and are released during
      the acrosome reaction induced by calcium ionophore A23187. These findings provide
      additional clues for elucidating the mechanisms involved in the sperm/egg
      interactions, including penetration of the zona pellucida by sperm.

PMID- 9588172
TI  - Role of carboxyl residues surrounding heme of human cytochrome b5 in the
      electrostatic interaction with NADH-cytochrome b5 reductase.
AB  - To identify the cytochrome b5 residues responsible for the electrostatic
      interaction with NADH-cytochrome b5 reductase (b5R), we prepared and
      characterized the cytochrome b5 mutants in which Glu41, Glu42, Glu63, Asp70, and
      Glu73 were replaced by Ala, utilizing site-directed mutagenesis and the
      expression system for cytochrome b5 in Escherichia coli. Apparent Km values of
      the wild type b5R for Glu42Ala cytochrome b5 and Asp70Ala cytochrome b5 were
      approximately three-fold and six-fold higher than that for the wild type
      cytochrome b5, respectively, while the kcat values for those mutants were not
      remarkably affected. In contrast, Glu41Ala, Glu63Ala, and Glu73Ala cytochrome b5
      showed almost the same kinetic properties as the wild type cytochrome b5.
      Furthermore, kinetic studies on combinations of the cytochrome b5 and b5R mutants
      suggested the interaction between Glu42 and Asp70 of cytochrome b5 and Lys125 and
      Lys41 of b5R, respectively, in the reaction.

PMID- 9588173
TI  - Analysis in Escherichia coli of the effects of in vivo CpG methylation catalyzed
      by the cloned murine maintenance methyltransferase.
AB  - Due in part to the complexity of mammalian systems, some of the proposed
      biological influences of mammalian DNA methylation have not been fully
      established. Escherichia coli cells, which normally contain negligible CpG
      methylation, exhibited progressive slowing of replication and lengthened
      generation times when expressing the murine DNA maintenance methyltransferase.
      Genomic analysis indicated significant amounts of CpG methylation in expressing
      cells which was absent from control cells. Expressing cells exposed to the
      cytosine demethylating agent, 5-azacytidine, rapidly reverted to propagation
      levels of controls. Substitution of cysteine with alanine in the carboxyl
      terminal region proline-cysteine dipeptide of the methyltransferase completely
      inactivated methylating activity and cells expressing the inactive enzyme
      replicated as well as controls. These findings strongly implicate a role of
      epigenetic de novo CpG methylation in modulating cellular propagation,
      demonstrate that the maintenance methyltransferase can de novo methylate in vivo,
      and show that the methyltransferase requires an active site cysteine for
      activity.

PMID- 9588174
TI  - Isolation and characterization of a rheumatoid arthritis-specific antigen (RA
      A47) from a human chondrocytic cell line (HCS-2/8).
AB  - Two types of 47 kDa antigen specifically recognized by sera from rheumatoid
      arthritis (RA) patients were isolated from the membrane fraction of a human
      chondrosarcoma-derived chondrocytic cell line (HCS-2/8) by a 2-step procedure:
      preparative SDS-PAGE and reverse-phase HPLC. An N-terminal amino acid sequence in
      one of the 47 kDa antigens, named RA-A47, had 81% homology to that deduced from
      the DNA sequence of the colligin gene which is reported as human hsp47 gene, and
      100% homology to that deduced from the DNA sequence of colligin-2 gene, a
      homologue of colligin. The RA-A47 cross-reacted with a monoclonal antibody raised
      against chick heat shock protein (Hsp) 47 and bound to gelatin. The expression of
      the ra-a47 gene was enhanced by heat shock treatment and TGF-beta stimulation.
      These findings suggest that RA-A47 is a Hsp47-like protein, presumably the
      product of the colligin-2 gene, and that a collagen-specific molecular
      chaperone(s) such as Hsp47 and/or RA-A47 is involved in cartilage destruction in
      RA.

PMID- 9588175
TI  - Compartmentalization of phosphatidylinositol 4,5-bisphosphate in low-density
      membrane domains in the absence of caveolin.
AB  - In cells that exhibit caveolae, the hormone-sensitive pool of PtdIns 4,5-P2 is
      localized in a low density, caveolin-enriched membrane fraction (1). Neuro 2a
      cells do not express caveolin. Nonetheless, the PtdIns 4,5-P2 in these cells is
      compartmentalized in a low density, detergent-insoluble domain that also contains
      other signaling-related molecules. Compartmentalization of PtdIns 4,5-P2 was
      observed regardless of whether Triton X-100-containing or detergent-free methods
      were used to prepare the membranes. However, the partitioning of receptor
      tyrosine kinases and GPI-anchored proteins into the low density domains was
      dependent upon the method of membrane preparation. Treatment of Neuro 2a cells
      with cyclodextrin delocalized the PtdIns 4,5-P2 and inhibited hormone-stimulated
      PtdIns turnover. These results suggest that compartmentalization of PtdIns 4,5-P2
      does not require caveolin but is necessary for the proper functioning of
      phosphoinositide-based signaling.

PMID- 9588176
TI  - Prevention of tumor necrosis factor (TNF)-mediated induction of p21WAF1/CIP1
      sensitizes MCF-7 carcinoma cells to TNF-induced apoptosis.
AB  - The MCF-7 breast carcinoma and MRC-5 lung fibroblast cell lines are sensitive and
      resistant to tumor necrosis factor (TNF)-induced apoptosis, respectively. As the
      cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) is involved in cell cycle
      regulation and has been implicated in apoptosis, we studied the influence of p21
      on growth of MRC-5 cells and on growth and apoptosis in MCF-7 cells. TNF induced
      p21 mRNA and protein in both cell types. p21 induction by > 0.5 ng/ml TNF in MRC
      5 and MCF-7 cells correlated with the inhibition of cell growth. In contrast, <
      0.1 ng/ml TNF stimulated MRC-5 (but not MCF-7) cell growth without reduction in
      p21 levels. TNF-induced apoptosis in MCF-7 cells was first detected after the TNF
      mediated increase in p21 and growth arrest had occurred. MCF-7 cells stably
      transfected with antisense p21 cDNA became more sensitive to TNF-induced
      apoptosis. Thus, TNF-induced p21 accompanied by growth arrest may counteract or
      delay TNF cytotoxicity in MCF-7 cells.

PMID- 9588177
TI  - Structural significance of the benzoyl group at the C-3'-N position of paclitaxel
      for nitric oxide and tumor necrosis factor production by murine macrophages.
AB  - The antitumor agent paclitaxel (Taxol) mimics the actions of lipopolysaccharide
      (LPS) on murine macrophages (M phi). Recently, we have shown that the benzoyl
      group at the C-3' position of paclitaxel is the most important site to induce
      nitric oxide (NO) and tumor necrosis factor (TNF) production by C3H/HeN M phi
      (Biochem. Biophys. Res. Commun. 210, 678-686, 1996). In the present study,
      synthetic analogs of paclitaxel with replacement of the C-3'-N position were
      examined for their potencies to induce NO and TNF production by peritoneal M phi
      of LPS-responsive C3H/HeN mice and LPS-hyporesponsive C3H/HeJ mice, by human
      blood cells and human M phi. In this structure-activity relationship study, we
      found that (i) the p-substitution of the benzoyl group definitely affects the
      activity to activate C3H/HeN M phi, (ii) the analogs having a methyl or chloro
      group at the p-position exhibit stronger activity than that of paclitaxel, (iii)
      there is good correlation between NO and TNF production by the M phi in response
      to compounds, (iv) the compounds tested do not induce either NO or TNF production
      by C3H/HeJ M phi or TNF production by human cells, (v) a previous treatment of
      C3H/HeN M phi with the inactive compounds can hardly affect either paclitaxel- or
      LPS-induced TNF production by the M phi, (vi) paclitaxel and its analogs
      marginally affect LPS-induced TNF production by human blood cells, and (vii)
      there is no correlation between the NO/TNF inducibility to C3H/HeN M phi and
      growth inhibitory activity against M phi-like J774.1 and J7.DEF3 cells.

PMID- 9588178
TI  - Preferential hydrolysis of oxidized phosphatidylcholine in cholesterol-containing
      phosphatidylcholine liposome by phospholipase A2.
AB  - Hydrolysis of 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC) hydroperoxide
      (PLPC-OOH) in PLPC liposomal membrane by Crotalus adamanteus venom phospholipase
      A2 (PLA2) was studied by measuring the decay of PLPC and PLPC-OOH and the
      formation of linoleate and linoleate hydroperoxide. We demonstrate that PLA2 has
      a preference to hydrolyze PLPC-OOH over PLPC when more than 25 mole % of
      cholesterol is incorporated into the PLPC liposomal membrane. Similar results
      were obtained for PLPC hydroxide (PLPC-OH). These results suggest that
      cholesterol displaces the hydrophilic hydroperoxyl and hydroxyl moieties of PLPC
      O(O)H to the surface interface of the liposomal membrane where they are more
      accessible to PLA2 hydrolysis.

PMID- 9588179
TI  - Structure of human endothelin-2 gene and demonstration of common expression in
      human right atrial tissue.
AB  - The endothelins (ET) are a group of three vasoactive peptides also known to be
      involved in vascular remodeling. ET1 is the most extensively studied, but recent
      evidence has highlighted the role of the little investigated ET2 gene as a
      potential candidate gene in regulating blood pressure. To allow the future role
      of this gene to be studied the structure of human ET2 was characterized and
      intron/exon boundaries were determined. With this structural information and
      using reverse-transcriptase PCR technology we show that the ET2 gene is commonly
      expressed in human right atrial tissue. This work will allow a more detailed
      assessment of the role of this physiologically important gene in human essential
      hypertension.

PMID- 9588180
TI  - Extended analysis of AL-amyloid protein from abdominal wall subcutaneous fat
      biopsy: kappa IV immunoglobulin light chain.
AB  - In AL-amyloidosis the cause of amyloid fibril formation in beta-pleated sheets
      from the precursor protein immunoglobulin light chain is not established, but
      studies of AL-proteins indicate that amino acid substitutions are important in
      the pathogenesis. Amyloid material was extracted from a subcutaneous fat tissue
      biopsy and submitted to extended protein separation, typing and amino acid
      sequence analyses. The AL-protein belonged to the rare immunoglobulin light chain
      kappa, subtype kappa IV and contained unique amino acid substitutions, mostly in
      the highly preserved framework regions. The study shows that subcutaneous fat
      biopsies are useful sources of amyloid material for biochemical studies.

PMID- 9588181
TI  - Inducible nitric oxide synthase (iNOS) expression in human monocytes triggered by
      beta-endorphin through an increase in cAMP.
AB  - Evidence suggesting a relationship between neuroendocrine and immune systems is
      steadily growing. We demonstrate now that inducible nitric oxide synthase (iNOS)
      is expressed in human peripheral blood monocytes after incubation of
      lymphomononuclear cells in the presence of beta-endorphin, a neuropeptide
      released by the pituitary in response to mental or physical stress or by
      activated lymphocytes. beta-endorphin raised cAMP level in monocytes. The
      possible relationship between cAMP and iNOS expression on monocytes was
      investigated. Immunostaining for iNOS decreased, when besides beta-endorphin an
      inhibitor of protein kinase A (H-89) was added to the medium at the beginning of
      the incubation. The cAMP level raised by beta-endorphin was lowered by naloxone,
      which also reduced slightly iNOS expression. These results clearly point to the
      monocyte as a link between neuroendocrine and immune systems, an observation of
      potential relevance in our understanding of how stress and autoimmunity could be
      interconnected.

PMID- 9588182
TI  - Mutation in the pleckstrin homology domain of the human phospholipase C-delta 1
      gene is associated with loss of function.
AB  - The delta-type phospholipase C (PLC) is thought to be evolutionally the most
      basal form in the mammalian PLC family. One of the delta-type isoforms, PLC-delta
      1, binds to both phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and
      inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) with a high affinity via its
      pleckstrin homology (PH) domain. We report here a missense mutation in the region
      encoding the C-terminal PH domain of the human PLC-delta 1. This is also the
      first report of a mutation in the human PLC genes. A single base substitution (G
      to A) causes the amino acid replacement, Arg105 to His. Site-directed mutagenesis
      of the glutathione-S-transferase (GST)/PLC-delta 1 fusion protein changing Arg105
      to His resulted in a fourfold decrease in the affinity of specific Ins(1,4,5)P3
      binding and a reduction in PtdIns(4,5)P2 hydrolysing activity to about 40% of
      that of the wild-type enzyme. This remarkable loss of function can be interpreted
      in terms of a conformational change in the PH domain.

PMID- 9588183
TI  - Involvement of specific mechanism in plasmid DNA uptake by mouse peritoneal
      macrophages.
AB  - The binding and uptake of plasmid DNA encoding luciferase reporter gene (pCMV
      Luc) were studied in vitro using cultured mouse peritoneal macrophages. A
      significant and time-dependent cellular association of [32P]pCMV-Luc with
      resident macrophages was observed at 37 degrees C and this decreased at 4 degrees
      C. The binding at 4 degrees C was saturable and a Scatchard plot gave a maximum
      binding capacity of 0.81 microgram/mg-protein and a dissociation constant of 0.30
      microgram/ml. The binding of [32P]-pCMV-Luc was inhibited by polyinosinic acid,
      dextran sulfate and salmon sperm DNA, but not by polycytidylic acid, dextran and
      EDTA. A confocal microscopic study demonstrated that fluorescein-labeled pCMV-Luc
      was internalized at 37 degrees C while only cell surface binding occurred at 4
      degrees C. No significant luciferase gene expression was obtained after
      incubation with a high concentration (100 micrograms/ml) of pCMV-Luc. These data
      suggest that plasmid DNA is taken up by macrophages via a mechanism mediated by a
      receptor like the macrophage scavenger receptor.

PMID- 9588185
TI  - Rhodocytin, a functional novel platelet agonist belonging to the heterodimeric C
      type lectin family, induces platelet aggregation independently of glycoprotein
      Ib.
AB  - We isolated and characterized a functionally novel platelet agonist, designated
      as rhodocytin, from the Calloselasma rhodostoma venom. Rhodocytin was a disulfide
      linked heterodimer consisting of 18- and 15-kDa subunits. The respective N
      terminal amino acid sequences of both subunits were homologous to each other and
      to those of the carbohydrate-recognition domains (CRD) of C-type lectins.
      Rhodocytin alone induced platelet aggregation. Platelet agonists and antagonists
      constructed with CRD-like subunits from snake venoms bind to glycoprotein Ib
      directly or indirectly. However, rhodocytin induced platelet aggregation not by
      binding to glycoprotein Ib, because rhodocytin-induced platelet aggregation was
      not influenced by echicetin, a glycoprotein Ib-binding protein, that completely
      inhibits platelet agglutination by bovine von Willebrand factor. These findings
      indicate that rhodocytin is a novel protein structurally related to heterodimers
      of CRD-like subunits, but functionally distinct from venom proteins that induce
      platelet aggregation via glycoprotein Ib.

PMID- 9588184
TI  - Immunohistochemical evidence for a macrophage scavenger receptor in Mato cells
      and reactive microglia of ischemia and Alzheimer's disease.
AB  - Macrophage scavenger receptors (MSR) are implicated in the development of
      atherosclerosis and amyloid b-protein deposition in Alzheimer's disease. However,
      histopathological studies of MSR expression in human tissues have been hampered
      by a lack of specific antibodies. Using MSR-deficient mice, we successfully
      raised a novel monoclonal antibody against human MSR together with high-titer
      antisera. These antibodies specifically recognized human tissue macrophages and
      human MSR protein purified from differentiated THP1 cells. In normal brain, MSR
      staining was mainly distributed to the perivascular cells, which correspond to
      Mato's fluorescent granular perithelial cells (Mato cells). In the lesions of
      ischemia and Alzheimer's disease, a subset of microglia stained positive for MSR.
      These novel antibodies are useful tools for analysis of MSR expression in human
      tissues.

PMID- 9588186
TI  - The heart of metamorphosing Mexican axolotl but not that of the cardiac mutant is
      associated with the upregulation of Hox A5.
AB  - The Mexican axolotl (Ambystoma mexicanum) is a facultative neotene which rarely
      undergoes metamorphosis in the wild. We now report for the first time a dramatic
      increase in the expression of HoxA5 in axolotl hearts as determined by RT-PCR and
      in situ hybridization analyses during spontaneous metamorphosis. The Mexican
      axolotl has a naturally occurring mutation called gene c which allows hearts in
      homozygous (c/c) embryos to form but never to beat. RT-PCR analysis has not shown
      any significant differences of HoxA5 expression in normal and mutant hearts. The
      predicted open reading frame of our already published partial cDNA clone of HoxA5
      was confirmed by expressing it as a fusion protein with Glutathione transferase
      (GST fusion protein). Phylogenetic analysis with the deduced amino acid sequence
      of the isolated cDNA of the axolotl homolog of the murine HoxA5 shows that the
      axolotl sequence clusters more closely with the human and mouse HoxA5 homologs
      than with axolotl sequence. Western blot analysis revealed that anti-mouse HoxA5
      antibody recognizes the axolotl HoxA5 protein.

PMID- 9588187
TI  - Differential expression of the p27Kip1 mRNA in IFN-sensitive and resistant cell
      lines.
AB  - IFNs arrest the growth of a small cell lung cancer (SCLC) cell line NCI-H82 in
      the G1 phase but not the growth of the derived cell line NCI-H82R. Progression
      through the G1 phase is controlled by positive and negative regulatory genes.
      Oncoviral genes can override this control. In this study, we compared the effects
      of human IFN alpha 2b on the mRNA levels of the Cdk inhibitor p27Kip1 in NCI-H82,
      NCI-H82R and HPV 16 E7-transfected NCI-H82 cell lines. Induction of the 2-5
      Oligoadenylate synthetase (2-5 OAS) gene was used as a marker of IFN-dependent
      signal transduction The expression of p27Kip1 mRNA increased at 48 and 72 hr
      after IFN alpha 2b addition in sensitive cells. In contrast, p27Kip1 mRNA had
      only slight variations in both the resistant and E7-transfected cells.
      Interestingly, the E7-transfected NCI-H82 cells became resistant to the IFN alpha
      2b anti-proliferative effect. Our results suggest that p27Kip1 could be a key
      mediator of the IFN alpha 2b-induced growth arrest and that HPV 16 E7 might
      affect p27Kip1 inducibility, originating IFN alpha 2b-resistant cells.

PMID- 9588188
TI  - Thrombin per se does not induce tyrosine protein phosphorylation in human
      platelets as judged by western blotting, while collagen does: the significance of
      synergistic, autocrine stimulation.
AB  - Thrombin elicits responses in platelets such as shape change, aggregation,
      arachidonate liberation and secretion of the contents of three storage granules,
      processes that coincide with serine/threonine and tyrosine phosphorylation of
      numerous proteins, hydrolysis of polyphosphoinositides and mobilisation of Ca2+
      within the cell. However, the significance of these parallel signal transduction
      processes has not been clearly elucidated in the light of the prevalent autocrine
      stimulation in platelets: a great amplification of the thrombin signal through
      secreted ADP, by production of thromboxane A2 from the liberated arachidonic
      acid, by the close cell contact produced by aggregation caused by exposure of
      integrin receptors that become ligated by fibrinogen and other platelet-produced
      factors. In the present communication five pathways of autocrine stimulation have
      been prevented by appropriate inhibitors. Under these conditions thrombin
      stimulated platelet secretion with little tyrosine phosphorylation, except for a
      125-130 kDa protein that was tyrosine-phosphorylated in response to one of the
      inhibitors, the peptide Arg-Gly-Asp-Ser (RGDS) used to block aggregation. In
      sharp contrast, collagen elicits massive tyrosine phosphorylation and platelet
      secretion in the absence of autocrine stimulation. When the thrombin-induced
      tyrosine phosphorylations was corrected for RGDS-induced phosphorylation, the
      presence of inhibitors of autocrine stimulation reduced the thrombin-induced
      phosphorylation by 97%. Our results strongly suggests that tyrosine
      phosphorylation is not part of the signal transduction pathway initiated by
      thrombin per se, but it represents an integral part of signal transduction
      initiated by collagen.

PMID- 9588189
TI  - Bactericidal domain of lactoferrin: detection, quantitation, and characterization
      of lactoferricin in serum by SELDI affinity mass spectrometry.
AB  - Lactoferricin is a bioactive peptide fragment (3196 Da) derived from lactoferrin
      (80 kDa) that contains the bactericidal domain and the lymphocyte receptor
      binding domain of lactoferrin. Although lactoferricin has been produced from
      lactoferrin by proteolytic digestion in vitro, its natural occurrence and
      distribution in vivo are still not clear, in part because of the absence of a
      suitable detection means. Surface-enhanced laser desorption/ionization (SELDI)
      was used to detect and characterize lactoferricin by affinity mass spectrometry.
      Human, porcine, and bovine lactoferricin in unfractionated serum samples were
      found to bind specifically to ligands presenting a terminal n-butyl group. SELDI
      was used to detect and quantify each species of lactoferricin in a manner that
      was independent of the presence of intact lactoferrin, partially degraded
      lactoferrin, and lactoferrin peptides containing the lactoferricin peptide
      sequence. The limit of detection of bovine lactofericin in serum was as low as
      200 pg/ml. The FKCRRWQWR-homoserine/-homoserine lactone moiety of bovine
      lactoferricin, which includes the complete antimicrobial center (i.e., RRWQWR),
      was shown to be responsible for interaction with the n-butyl group. The SELDI
      procedure defined here is the only molecular recognition tool known to date that
      is capable of distinguishing the multi-functional lactoferricin domain located
      within structurally related but distinct forms of lactoferrin and its metabolic
      fragments. Enabling the direct quantitation of lactoferricin produced in vivo
      opens new opportunities to evaluate lactoferrin function.

PMID- 9588190
TI  - Reduction of Cripto-1 expression by a hammerhead-shaped RNA molecule results from
      inhibition of translation rather than mRNA cleavage.
AB  - Cripto-1 (CR-1) is a transforming growth factor which has been associated with
      breast, colon, and pancreatic cancer. Overexpression of CR-1 in non-tumorigenic
      mouse mammary epithelial cells and fibroblasts results in an increase in
      anchorage-dependent and -independent growth in vitro. Reduction of CR-1
      expression in human colon carcinoma or embryonal teratoma cells results in a
      decrease in growth in vitro. In an effort to better define the role of CR-1 in
      breast cancer, we have developed an underexpression vector for CR-1 to reduce CR
      1 levels in a tumorigenic mouse mammary epithelial cell line (-SA). This vector
      specifically targets the expression of the murine homolog of CR-1 in murine
      cancer lines and utilizes a hammerhead ribozyme-like structure directed toward
      the extreme 5' end of the Cripto-1 mRNA. We dramatically reduced expression of CR
      1 through the expression of this RNA. This is the first use of a ribozyme-like
      molecule to alter Cripto-1 expression. This ribozyme-shaped molecule appears to
      act principally through a block in translation. A possible mechanism for this
      block is described, and its implications for modifying expression of other
      bioactive proteins are discussed.

PMID- 9588191
TI  - Diversity in the variable region of Helicobacter pylori cagA gene involves more
      than simple repetition of a 102-nucleotide sequence.
AB  - CagA, a product of cytotoxin-associated gene A cagA, is an important virulence
      related antigen of Helicobacter pylori (HP). CagA varies in size from 128 kDa to
      about 140 kDa and this variation is believed to be generated by a 102-nucleotide
      (NT) repeat sequence in the so-called variable region of cagA. However, this
      explanation has not previously been tested by comparing the NT sequences of cagA
      derived from a number of different isolates of HP. In this study we first
      compared the size of PCR products obtained from 54 different isolates of HP with
      oligonucleotide primers designed to amplify a cagA fragment predicted to be at
      least 1059 NT, including the variable region of the gene. As expected, the size
      of the PCR products varied considerable, from 1110 to 1822 NT, but the majority
      (50 of 54) measured 1335 NT or less. The deduced amino acid (AA) sequences of 9
      representative amplicons and 4 other known sequences were compared with the
      following result: Within the variable region of cagA there are actually two
      adjacent variable regions, which we label as proximal and distal. The proximal
      variable region of CagA extends from a motif of 4 to 6 asparagine residues to a 7
      AA repeat sequence (KIDQLNQ); the distal-variable region is confined between
      KIDQLNQ and a well-conserved duplicate, KIDNLNQ. Despite these shared features
      CagA of every HP strain examined to date has a variable region with a unique AA
      sequence.

PMID- 9588192
TI  - Implication of altered redox regulation by antioxidant enzymes in the increased
      plasma pentosidine, an advanced glycation end product, in uremia.
AB  - Pentosidine is an advanced glycation end product (AGE) formed during Maillard or
      browning reaction by non-enzymatic glycation and oxidation (glycoxidation).
      Recent studies demonstrated the increased plasma pentosidine levels not only in
      diabetic patients with hyperglycemia but also in normoglycemic uremic patients.
      The mechanism of increased glycoxidation reaction in uremia, however, remains
      unknown. As superoxide dismutases (SODs) and glutathione peroxidase (GPx) are
      antioxidant enzymes involved in the metabolism of H2O2 which accelerates the
      glycoxidation reaction, we measured their activities by enzymatic assays in the
      plasma of normal and non-diabetic hemodialysis patients and examined a link
      between redox regulation by antioxidant enzymes and glycoxidation reaction. The
      activities of GPx were significantly lower in the plasma of hemodialysis patients
      than in normal subjects, whereas those of SODs were higher in the former than in
      the latter. As plasma SODs comprise three isozymes, i.e., Cu/Zn-SOD, Mn-SOD, and
      extracellular (EC)-SOD, we determined the levels of each SOD isozyme by ELISAs.
      The plasma concentrations of Cu/Zn-SOD and EC-SOD were significantly higher in
      hemodialysis patients than in normal subjects, whereas those of Mn-SOD did not
      differ between the two groups. It is of note that GPx activities correlated
      inversely with pentosidine in the plasma of hemodialysis patients (r2 = 0.262, P
      < 0.01). There was no significant correlation between total SOD activities and
      pentosidine levels in the plasma of hemodialysis patients, but, among the three
      SOD isozymes, the plasma EC-SOD levels correlated with the levels of pentosidine
      in hemodialysis patients (r2 = 0.286, P < 0.05). As decreased GPx and increased
      SOD activities result in the increased H2O2 generation, which accelerates the
      glycoxidation of protein, these data suggest a link of altered redox regulation
      by antioxidant enzymes to increased glycoxidation reaction in the uremic plasma.
      This paper provides the first time evidence for the possible involvement of
      enzymatic redox regulation in the non-enzymatic glycoxidation reaction in vivo.

PMID- 9588193
TI  - Structure of catechol 2,3-dioxygenase gene from Alcaligenes eutrophus 335.
AB  - Catechol 2,3-dioxygenase (C23O), one of extradiol-type dioxygenases cleaving
      aromatic C-C bond at meta position of dihydroxylated aromatic substrates,
      catalyzes the conversion of catechol to 2-hydroxymuconic semialdehyde. As our
      ongoing study to characterize biochemical and genetic properties of the extradiol
      type dioxygenases at molecular level, a C23O gene encoded in chromosomal DNA of
      Alcaligenes eutrophus 335, a strain degrading phenol and p-cresol, was cloned.
      The C23O gene was localized in an 1.4-kb PstI fragment from A. eutrophus 335, and
      was expressed in E. coli HB101. The C23O exhibited the highest aromatic ring
      fission activity to catechol as a substrate, and its relative activity to other
      dihydroxylated aromatic substrates was in order of catechol >> 4-methylcatechol >
      3-methylcatechol, protocatechuate, 4-chlorocatechol > 3,4-dihydroxy-phenylacetate
      > 2,3-dihydroxybiphenyl. Nucleotide sequence of the 1.4-kb fragment has revealed
      that an open reading frame (ORF) corresponding to the C23O gene was composed of
      930 base pairs. A putative ribosome-binding sequence of AGGAG was found at about
      10 nucleotides upstream the ORF which can encode a polypeptide of molecular
      weight 34 kDa consisting of 309 amino acid residues. The deduced amino acid
      sequence of C23O from A. eutrophus 335 exhibited the highest 59% identity with
      those of corresponding enzymes from Pseudomonas sp. CF600 (p VI150), P. putida
      HS1 (pDK1), and P. putida PpG7 (NAH7). An alignment of amino acid sequences of
      extradiol-type dioxygenases including C23O from A. eutrophus 335 has revealed
      that catalytically and structurally important amino acid residues of the enzymes
      were conserved during evolution.

PMID- 9588194
TI  - Chemotherapeutic drug activation of the AP24 protease in apoptosis: requirement
      for caspase 3-like-proteases.
AB  - AP24 is a serine protease that is activated during TNF or UV light-induced
      apoptosis and stimulates DNA fragmentation in isolated nuclei. The present study
      determined whether apoptosis induced by chemotherapeutic drugs resulted in
      activation of AP24 and examined the possible relationship to caspase activity. We
      showed that an inhibitor of AP24, DK120, could block DNA fragmentation induced in
      three leukemia cell lines (U937, HL-60, and CEM) by various DNA-damaging drugs
      including etoposide, camptothecin, chlorambucil, and the CC1065-related drug,
      YW201. Etoposide-induced activation of intracellular DEVD-pNa cleaving activity
      and apoptosis was suppressed by low micromolar concentrations of cell-permeable
      inhibitors of caspase-3. Furthermore, these inhibitors also suppressed activation
      of AP24. In contrast, DK120 did not prevent etoposide activation of DEVD-pNa
      cleaving activity, nor did it prevent cleavage of poly(ADP-ribose) polymerase.
      AP24 isolated from apoptotic cells following treatment with etoposide activated
      DNA fragmentation in isolated normal nuclei and was inhibited by DK120, but not
      by caspase inhibitors. This evidence shows that activation of caspase 3-like
      proteases generates signals that contribute to the activation of AP24 which may
      then induce nuclear DNA fragmentation in chemotherapeutic drug-induced apoptosis.

PMID- 9588195
TI  - Aquaporin-1: an osmoinducible water channel in cultured mIMCD-3 cells.
AB  - The expressions of aquaporin-1 (AQP-1) in cultured mIMCD-3 cells were studied.
      There was no detectable AQP-1 in cells grown in serum-containing growth medium
      (SM, 297 +/- 2 mOsm/kg. H2O). When SM was supplemented with NaCl (406 +/- 2
      mOsm/kg. H2O), cellular AQP-1 was induced. A further increase in medium
      osmolarity with NaCl (493 +/- 3 mOsm/kg. H2O) had conferred cells an 2.5 to 3
      fold increase of AQP-1 expression over those grown in the 406 +/- 2 mOsm/kg. H2O
      medium. Moreover, AQP-1 was found to be translocated from cytosol to membrane. In
      addition, exposing the mIMCD-3 cells to vasopressin (AVP, 10(-8) M) and/or NaCl
      supplemented serum-free media (496 +/- 3 mOsm/kg. H2O) for 6h did not render them
      to produce AQP-1. However, AQP-1 was induced after 24h of incubation, with an 1.5
      fold additive effect by AVP. Our RT-PCR data had confirmed the NaCl inducibility
      and AVP synergism in AQP-1 expression at both mRNA and protein levels. This
      suggests a new role for cellular AQP-1 and AVP in overcoming osmotic stress in an
      in vitro system.

PMID- 9588196
TI  - Purification and characterisation of a tissue specific elongation factor 1 alpha
      (EF-1 alpha 2) from rabbit muscle.
AB  - The peptide elongation factor 1 alpha (EF-1 alpha) has been isolated and
      characterised from a number of species. Recently we and others have reported the
      existence of an isoform of the ubiquitously expressed EF-1 alpha mRNA in higher
      eukaryotes, including human cells. This isoform has a tissue specific expression
      pattern, confining it primarily to muscle, heart, and brain. In the present study
      we have purified the isoform of EF-1 alpha from rabbit muscle. Using partial
      amino acid analysis, we can conclude that in rabbit muscle essentially only the
      isoform of elongation factor 1 alpha, designated EF-1 alpha 2, is translated.
      Preliminary activity assays show that the isoform has the same functional
      activities as the normal EF-1 alpha, designated EF-1 alpha 1, in relation to
      protein synthesis, but may behave differently in the ability to bind nucleotides.
      Based on the availability of the isoforms of EF-1 alpha purified from a mammalian
      species, it will be possible to conduct further comparative studies in order to
      elucidate the different functions of EF-1 alpha 1 and EF-1 alpha 2 proteins.

PMID- 9588197
TI  - Metallothionein-mediated resistance to multiple drugs can be induced by several
      anticancer drugs in mice.
AB  - We examined the role of metallothionein in the chemosensitivity of transplanted
      tumors in mice. The antitumor activities of cisplatin, adriamycin, bleomycin,
      peplomycin, cyclophosphamide, and melphalan were significantly suppressed when
      the concentration of metallothionein in the tumor was increased to only twice the
      control level. On the other hand, the antitumor activities of mitomycin C, 5
      fluorouracil, and vinblastine were hardly affected by increases in the
      concentration of metallothionein in the tumors in mice. Moreover, all the
      antitumor drugs examined increased the concentration of metallothionein in
      transplanted tumors to a level that was high enough to suppress the antitumor
      activity of these drugs. These observations suggest that treatment of patients
      with certain antitumor drugs might result in the resistance of their tumors to
      multiple drugs.

PMID- 9588198
TI  - TIP49, homologous to the bacterial DNA helicase RuvB, acts as an autoantigen in
      human.
AB  - TATA-binding protein (TBP), a central component for transcriptional regulation,
      forms complexes with various transcription regulators. We have isolated a novel
      human cDNA for a 49-kD TBP-interacting protein (TIP49). The human TIP49 was
      highly homologous to bacterial RuvB proteins that function as a DNA helicase to
      promote branch migration of the Holliday junction. Immunofluorescence analysis
      using anti-TIP49 antibody showed a typical dot-shaped nuclear staining pattern,
      suggesting that TIP49 is included in a macromolecular structure in the nucleus
      and may participate in nuclear events such as transcription and recombination.
      Moreover, glycerol gradient analysis demonstrated that TIP49 is present in a
      macromolecular complex in nuclear extracts. Interestingly, we detected a high
      level of autoantibodies against TIP49 in sera of patients with autoimmune
      diseases such as polymyositis/dermatomyositis and autoimmune hepatitis. This
      indicates that the autoantibody against this protein is a new marker for
      particular connective tissue diseases. These findings provide further evidence
      that the macromolecular structures described above are targeted by an autoimmune
      mechanism. The anti-TIP49 antibodies can be useful probes for clinical diagnosis
      and for investigation of intranuclear structure.

PMID- 9588199
TI  - Sodium-dependent homo- and hetero-exchange of neutral amino acids mediated by the
      amino acid transporter ATB degree.
AB  - We have investigated the functional characteristics of the human amino acid
      transporter ATB degree using the Xenopus laevis oocyte expression system. When
      expressed in oocytes, ATB degree mediates the uptake of neutral amino acids in an
      Na(+)-dependent manner. In addition, this transporter is able to mediate the
      efflux of intracellular neutral amino acids in exchange with extracellular
      neutral amino acids. This homo- and hetero-exchange of amino acids is absolutely
      Na(+)-dependent and conforms strictly to the substrate specificity of ATB degree.
      Kinetic analysis indicates that the affinity of ATB degree for a given amino acid
      substrate is similar whether ATB degree catalyzes the influx of the amino acid or
      the amino acid-induced efflux of intracellular amino acids. These results
      demonstrate for the first time the ability of ATB degree to function as a homo-
      and hetero-exchanger for its substrates.

PMID- 9588200
TI  - Rho protein inhibition blocks protein kinase C translocation and activation.
AB  - Small GTP-binding proteins of the Ras and Rho family participate in various
      important signalling pathways. Large clostridial cytotoxins inactivate GTPases by
      UDP-glucosylation. Using Clostridium difficile toxin B-10463 (TcdB) for
      inactivation of Rho proteins (RhoA/Rac/Cdc42) and Clostridium sordellii lethal
      toxin-1522 (TcsL) for inactivation of Ras-proteins (Ras/Rac/Ral, Rap) the role of
      these GTPases in protein kinase C (PKC) stimulation was studied. Phorbol
      myristate-acetate (PMA) induced a rapid PKC translocation to and activation in
      the particulate cell fraction as determined by PKC-activity measurements and
      Western blots for PKC alpha. These effects were blocked by TcdB inhibiting Rho
      proteins in endothelial cells, but not in TcsL-treated cells (i.e., cells without
      Ras activity), suggesting that Rho GTPases (RhoA and/or Cdc42) are the most
      likely GTP-binding proteins responsible for PKC activation. The Rho requirement
      for PKC activation/translocation was also verified for human epithelial cells and
      for lipopolysaccharide-stimulated endothelial cells. In summary, the data
      presented indicate that Rho protein inhibition blocked PKC
      translocation/activation in endothelial and epithelial cells.

PMID- 9588202
TI  - High affinity binding of oxidized LDL to mouse lectin-like oxidized LDL receptor
      (LOX-1).
AB  - We cloned mouse LOX-1 cDNA to take advantage of a gene-targeting technique to
      clarify the role of LOX-1 in vivo. Mouse LOX-1 was composed of 363 amino acids
      and had a C-type lectin domain type II membrane protein structure. Mouse LOX-1
      had triple repeats of the sequence in the extracellular "Neck domain," which is
      unlike human and bovine LOX-1. LOX-1 bound oxidized LDL with two classes of
      binding affinity in the presence of serum. The binding component with the higher
      affinity showed the lowest value of Kd among the known receptors for oxidized
      LDL. In the absence of serum, the high affinity component disappeared, suggesting
      that an unknown co-factor in serum is essential for efficient uptake of oxidized
      LDL by endothelial cells. A low concentration of unlabeled oxidized LDL displaced
      125I-labeled oxidized LDL more efficiently in the presence of serum than in the
      absence of serum. The co-factor in the serum may be involved in the
      pathophysiology of atherosclerosis in addition to the oxidation of LDL.

PMID- 9588201
TI  - Acetylcholine acts on M3 muscarinic receptors and induces the translocation of
      aquaporin5 water channel via cytosolic Ca2+ elevation in rat parotid glands.
AB  - To evaluate the role of aquaporin5 (AQP5) in salivary secretion induced by
      cholinergic stimulation, the alteration of the distribution of AQP5 in rat
      parotid tissues induced by acetylcholine (ACh) was studied by immunobolt
      analysis. The treatment of the tissues with ACh within 1 min induced the
      translocation of AQP5 from intracellular membranes (ICM) to apical membranes
      (APM), but that for more than 5 min resulted in the converse translocation from
      APM to ICM. The ACh-induced increase in the amount of AQP5 in APM was inhibited
      by atropine, p-F-HHSiD and TMB-8, but not by methoctramine, staurosporine or H-7.
      The calcium ionophore A-23187 alone stimulated the translocation of AQP5 between
      APM and ICM. These results indicated that ACh acted on M3 muscarinic receptors
      and induced the translocation of AQP5 between ICM and APM, and that the cytosolic
      Ca2+ elevation by ACh may play a key role in this translocation in rat parotid
      glands.

PMID- 9588204
TI  - Molecular cloning of human gastric mucin MUC5AC reveals conserved cysteine-rich D
      domains and a putative leucine zipper motif.
AB  - To further clone the human gastric mucin MUC5AC cDNA, we screened a human gastric
      cDNA library with previously identified MUC5AC sequences. We obtained 32
      independent clones encoding newly identified sequences comprising the entire N
      terminal sequence of MUC5AC, up to 3024 bp upstream of the previously identified
      MUC5AC sequences. The N-terminus of MUC5AC shows high homology (43% identity)
      with the N-terminus of MUC2 and contains three domains homologous to the D
      domains found in the pro-von Willebrand factor. Furthermore, the N-terminus of
      MUC5AC contains a putative leucine zipper motif not found in any other mucin
      identified so far. Moreover, a large central repetitive sequence was identified
      encoding approximately 2500 amino acids (7.5 kb). We were able to establish that
      the MUC5AC cDNA together with the previously identified 6.1 kb of MUC5AC cDNA
      sequence is about 16.6 kb, encoding 5525 amino acids. A model of the domain
      structure of MUC5AC is presented.

PMID- 9588205
TI  - Presence of polysialic acid and HNK-1 carbohydrate on brain glycoproteins from
      beta-1,4-galactosyltransferase-knockout mice.
AB  - Polysialic acid and HNK-1 carbohydrate are expressed on Gal beta 1-->4GlcNAc
      outer chains of N-linked sugar chain of neural cell recognition molecules at
      certain developmental stages and involved in neural tissue formation. Targeted
      inactivation of the mouse beta-1,4-galactosyltransferase (beta-1,4-GalT) gene
      resulted in short life of the mice which supposedly do not have such carbohydrate
      antigens but have no defects in neural tissue formation. Analysis of the mutant
      mouse brain glycoproteins revealed that polysialic acid and HNK-1 carbohydrate
      are normally expressed in an age-dependent manner. In support of this, protein
      bands reacted with Ricinus communis agglutinin-I, which interacts with
      oligosaccharides terminated with the Gal beta 1-->4GlcNAc group, and beta-1,4
      GalT activity toward GlcNAc beta-S-pNP were detected in the mutant mouse brain,
      indicating that brain contains another functional beta-1,4-GalT important for the
      expression of the carbohydrate antigens.

PMID- 9588203
TI  - High-level secretion of biologically active recombinant porcine follicle
      stimulating hormone by the methylotrophic yeast Pichia pastoris.
AB  - An active recombinant glycoprotein hormone, porcine follicle-stimulating hormone
      (recFSH), has been produced for the first time in the methylotrophic yeast,
      Pichia pastoris. The yield of secreted recFSH (10 mg/l) was the highest ever
      reached. RecFSH displayed an apparent molecular mass of 41 kDa by SDS-PAGE and
      was found to bear only N-linked carbohydrates of the high-mannose type. Its in
      vitro binding and cell-stimulating activities were identical to those of
      pituitary porcine FSH. The large availability and the noncharged N-glycans of
      FSHrec should render it highly valuable for structural studies.

PMID- 9588206
TI  - Regulation of cytosolic proteins binding cis elements in the 5' leader sequence
      of the angiotensin AT1 receptor mRNA.
AB  - RNA binding proteins (BPs) have been identified which bind within a -271 to -174
      nt domain in the 5' leader sequence (5'LS) of the rat type 1 angiotensin (AT1)
      receptor mRNA and which encompass RNA cis elements upstream of -239. A 100 kDa
      RNA-protein complex is observed by UV-crosslinking in several tissues including
      brain, lung, and spleen. 5'LS RNA transcripts of the 1a and 1b AT receptor
      subtypes are strong competitors of 5'LS-protein complex formation. In contrast,
      antisense 5'LS AT1a transcripts, plasmid transcripts, poly U and poly A RNAs, or
      5'LS AT1a cDNA are poor competitors. Deoxycorticosterone acetate (DOCA) decreased
      5'LS-BP activities in the forebrain and hypothalamus under conditions known to
      significantly increase AT1 receptor expression. DOCA had no effect on 5'LS-BP
      activities in the pituitary which correlates with its lack of effect on pituitary
      AT1 receptor expression. These results indicate that DOCA differentially
      regulates 5'LS-BP activities in a tissue-specific manner and suggest that
      physiologically mediated changes in AT1 receptor expression are mediated by
      alterations in 5'LS-BP activities, which represents a previously unrecognized
      level of regulation for the renin angiotensin system.

PMID- 9588207
TI  - MyoD and MEF2A mediate activation and repression of the p75NGFR gene during
      muscle development.
AB  - In an effort to clarify transient expression of the NGF low-affinity receptor
      p75NGFR during muscle development we have focused on the molecular mechanisms
      involved in the initiation and cessation of p75NGFR gene expression. Using
      quiescent C3H10T1/2 fibroblast as a tool, we observed that induction of
      differentiation competence in MyoD-transfected 10T1/2 fibroblasts was accompanied
      by the initiation of p75NGFR expression. Moreover, we could show that the bHLH
      transcription factor MyoD itself is a powerful candidate for transcriptional
      activation of the p75NGFR gene in muscle precursor cells. By means of MyoD
      mutants we have found that both the amino terminus of the MyoD molecule as well
      as the bHLH-region are essential for transcriptional activity on the p75NGFR
      promoter. The fact that myocyte enhancer factor MEF2A inactivated MyoD-induced
      p75NGFR promoter activity strongly suggests that cell-specific regulation of the
      p75NGFR gene might be strictly dependent on the intracellular composition and
      balance of the appropriate bHLH-transcription factors and their modulators.

PMID- 9588208
TI  - The Dazh gene is expressed in male and female embryonic gonads before germ cell
      sex differentiation.
AB  - The autosomal homologs of the human Y-chromosomal DAZ gene (DAZH and Dazh in
      human and mouse, respectively) are strong candidate for Azoospermia factor and
      encode a testis specific RNA-binding proteins. We studied the expression pattern
      of the mouse Dazh during embryonic development by using Northern-blotting of
      developing gonads. In the mouse, we have detected 3.5 kb and 4.5 kb transcripts
      in male and female embryonic gonads at 12.5 dpc (days post coitum). During this
      period, the only germ cells present in the gonad are primordial germ cells. Dazh
      transcripts were not detected in embryonic gonads of mice that lack germ cells
      because of mutation in W gene, suggesting that expression is limited to germ
      cells. In females, oogonia enter meiosis at 13.5-14.5 dpc: at this time Dazh
      transcription levels are similar to those of the male (when prospermatogonia are
      in the male gonad). Transcription levels decrease steadily after birth as the
      number of oocytes is depleted and is hardly detectable by puberty. A human DAZH
      transcript was also detected by Northern-blotting in the human ovary in levels
      which are of about 100 fold lower than those observed in the human testis. The
      expression of the Dazh in male and female gonad before germ cell sex
      differentiation suggests that these genes may act at the first phase of male and
      female gametogenesis.

PMID- 9588209
TI  - A cytoplasmic AAA family peroxin, Pex1p, interacts with Pex6p.
AB  - Human PEX1 (HsPEX1) is the causative gene for peroxisome-deficiency disorders
      such as Zellweger syndrome of complementation group I, encoding the peroxin,
      Pex1p, a member of AAA family. Pex1p tagged with an epitope flag was expressed in
      wild-type Chinese hamster ovary (CHO) cell, CHO-K1. Pex1p was localized in the
      cytoplasm, as assessed by immunofluorescent microscopy. Cell-lysate of HsPEX1
      transfected CHO-K1 was incubated with in vitro synthesized 35S-labelled Pex6p, an
      AAA family peroxin. Immunoprecipitation of Pex1p using anti-Pex1p antibody
      resulted in concomitant recovery of 35S-Pex6p. Conversely, 35S-Pex1p was obtained
      in immunoprecipitate from CHO-K1 expressing human Pex6p, using anti-Pex6p
      antibody. These results strongly suggest that Pex1p and Pex6p interact with each
      other.

PMID- 9588210
TI  - Characterization of the mouse Myoc/Tigr gene.
AB  - Mutations in the myocilin (MYOC), also known as Trabecular meshwork-Inducible
      Glucocorticoid Response (TIGR) gene can lead to juvenile open-angle glaucoma in
      human and may be responsible for at least 3% of primary open-angle glaucoma. To
      develop a mouse model of primary open angle glaucoma, and to get deeper insight
      into the mechanisms of the MYOC/TIGR gene regulation and function, we have
      isolated and characterized full size mouse Myoc/Tigr cDNA and genomic clones. The
      mouse and human MYOC/TIGR genes have the same exon-intron structure and contain 3
      exons, although the mouse gene is 6 kb shorter than the human gene (10 kb versus
      16 kb) due to differences in the length of introns. The MYOC/TIGR gene encodes a
      moderately conserved protein, which is 82% identical between human and mouse. The
      encoded protein is 14 amino acids shorter at the N-terminus in the mouse than in
      the human (490 versus 504 amino acids). Mouse and human MYOC/TIGR genes show a
      similar pattern of expression in adult ocular and nonocular tissues. The mouse
      Myoc/Tigr gene was mapped to Chromosome 1 at position 82.8 cM from the
      centromere. All residues, which were identified in the human MYOC/TIGR protein as
      critical for glaucoma development, are conserved in the mouse Myoc/Tigr.

PMID- 9588211
TI  - Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia
      inducible factor-1 binding site on the antisense strand.
AB  - Endothelin-1 (ET-1) is a peptide hormone with potent vasoconstrictor properties
      that is synthesized and secreted predominantly by vascular endothelial cells. Its
      production is regulated by numerous stimuli including ischemia and hypoxia, and
      the enhanced levels that occur during myocardial ischemia may contribute to the
      progression of heart failure. We previously reported that ET-1 expression was
      induced by both hypoxia and transition metals in endothelial cells (ECs). Here we
      define an element in the proximal promoter of the ET-1 gene that is responsible
      for this induction. By using deletions and site directed mutagenesis of the human
      ET-1 promoter, in combination with electrophoretic gel mobility shifts and
      transient expression assays in human ECs, we identified an active hypoxia
      inducible factor 1 (HIF-1) binding site starting at position -118 upstream of the
      transcription start site on the non-coding DNA strand. Mutation of this site
      eliminated induction by hypoxia without affecting basal (aerobic) expression, and
      the mutated sequence did not display hypoxia-specific binding of HIF-1.

PMID- 9588212
TI  - A putative tumor suppressor, TSG101, acts as a transcriptional suppressor through
      its coiled-coil domain.
AB  - TSG101 is thought as a putative tumor suppressor gene, and mutations of this gene
      were recently found in 7 of 15 breast cancer patients, though the physiological
      function remains to be elucidated. In this report, we showed that TSG101 protein
      acts as a transcriptional suppressor for estrogen receptor (ER) as well as other
      members of the nuclear hormone receptor super-family, VP16, and on its own. The
      basal promoter activity was also inhibited by TSG101. The suppression of
      transcription by TSG101 protein required its coiled-coil domain, which is also
      shown to be required for the tumor suppressive function. Expressed TSG101 protein
      did not have any histone acetylase nor deacetylase activity, which certain
      transcriptional co-factors have. The requirement of the same domain in the TSG101
      protein for transcriptional suppression and in the tumor suppression indicates a
      possibility that transcriptional suppression of TSG101 is related to its tumor
      suppression.

PMID- 9588213
TI  - Angiostatin upregulates E-selectin in proliferating endothelial cells.
AB  - Angiostatin, a 38 kilodalton fragment of plasminogen, is a potent inhibitor of
      angiogenesis. However, little is known about how angiostatin affects endothelial
      gene expression. To learn more about its effect on endothelial-specific genes
      implicated in angiogenesis, we examined E-selectin expression and function in
      bovine capillary endothelial cells treated with recombinant angiostatin.
      Angiostatin caused a four to five-fold increase in E-selection polypeptide levels
      in proliferating endothelial cells but little or no increase in confluent cells.
      P-selection polypeptide levels were unaffected by angiostatin in either
      proliferating or confluent cells. E-selectin mRNA and adhesion activity in
      proliferating endothelial cells were also increased by angiostatin. Angiostatin
      had little effect on the distribution of endothelial cells in G0/G1, S, and G2/M,
      indicating angiostatin does not alter cell cycle progression significantly. These
      data demonstrate that angiostatin selectively upregulates E-selectin in
      proliferating endothelial cells in vitro. This selectivity may provide insights
      into the mechanism by which angiostatin inhibits tumor growth in vivo without
      apparent effects on quiescent endothelium.

PMID- 9588215
TI  - Resistance to apoptosis induced by topoisomerase I inhibitors in multidrug
      resistant HL60 leukemic cells.
AB  - The induction of apoptosis by topoisomerase I inhibitors, camptothecin and SN38,
      was evaluated in drug-sensitive HL60 and multidrug-resistant (MDR) HL60-Vinc
      leukemic cells. MDR cells displayed a partial resistance to these apoptotic
      stimuli and this phenomenon was not modulated by verapamil. Basal free calcium
      concentrations were similar in both cell sublines and were not modified during
      treatment. Cytoplasmic pH was more acidic in sensitive cells than in MDR cells.
      Moreover, a significant acidification was obtained during the early stage of
      apoptosis in sensitive HL60 cells only. Basal Bcl-2 protein expression was found
      to be greater in MDR than in sensitive cells and was not modulated by apoptosis
      inducers. This increase of Bcl-2 in MDR cells could be due to the selection
      process as vincristine enhances Bcl-2 phosphorylation and expression in HL60
      sensitive cells. MDR HL60-Vincristine cells therefore display a resistance to
      apoptosis induced by non-MDR drugs, possibly by Bcl-2 overexpression and
      inability of these drugs to mediate intracellular pH changes in these drug
      resistant cells.

PMID- 9588214
TI  - IGF I induction of p53 requires activation of MAP kinase in cardiac muscle cells.
AB  - The aim of this study was to investigate whether IGF I induction of p53
      expression and p21 promoter require activation of MAP kinase in cardiac muscle
      cells. Compared to cardiomyocytes transfected with control vector, activation of
      MAP kinase by IGF I was decreased by approximately 60-70% in the cells
      transfected with dominant negative MAP kinase Y185. Transfection with Y185 also
      resulted in decreased induction of p53 mRNA by IGF I (70% reduction). In the
      cells transfected with a wildtype p21WAF1/CIP1 promoter construct, activation of
      luciferase reporter gene by IGF I was decreased in the cells co-transfected with
      Y185. To further confirm these findings, cells were preincubated with PD98059, a
      specific MAP kinase kinase inhibitor. As expected, PD98059 inhibited induction of
      p53 mRNA and p21WAF1/CIP1 promoter by IGF I. These data indicate that
      transcriptional activation of p53 and p21WAF1/CIP1 by IGF I involves MAP kinase
      pathway in cardiomyocytes, and thus link MAP kinase to negative modulation of the
      cell cycle in cardiac muscle cells.

PMID- 9588216
TI  - Differential changes in transforming growth factor-beta isoform expression during
      postnatal cardiac growth.
AB  - Transforming growth factor-beta (TGF-beta) is synthesised as an inactive
      precursor protein; this is cleaved to produce the mature peptide and a latency
      associated protein (LAP), which remains associated with the mature peptide until
      activation by LAP degradation. Isoform specific antibodies raised against the
      LAPs for TGF-beta 2 and -beta 3 were used to determine the myocardial levels of
      LAP (activatable TGF-beta) and full length precursor (inactive TGF-beta) forms
      during post-natal development in the rat. TGF-beta 2 was present predominantly as
      the precursor in 2 day old myocardium. There was an age-dependent shift from
      precursor protein to LAP between 2 and 28 days. A corresponding increase in the
      level of mature (activatable) TGF-beta 2 was found. TGF-beta 3 was detected in
      significant quantities only as LAP. However, a four-fold increase in the
      expression of TGF-beta 3 LAP was observed between 2 and 28 days. The substantial
      increases in activatable forms of TGF-beta 2 and -beta 3 that occur in myocardium
      during the first 28 days of life in the rat support a role for these proteins in
      post-natal cardiac development.

PMID- 9588217
TI  - gp130 is involved in stretch-induced MAP kinase activation in cardiac myocytes.
AB  - We have recently reported that mitogen activated protein kinase (MAP kinase) is
      activated by the stretch of the cultured cardiac myocytes in the angiotensin II
      deficient state in the angiotensinogen-deficient mice (Atg-/-), suggesting that
      factors other than the cardiac renin-angiotensin system are involved in the
      stretch-induced MAP kinase activation. We examined the contribution of cytokines
      using RX435, an anti-gp130 antibody. Leukemia inhibitory factor, which is one of
      the cytokines and has the common receptor subunit gp130, activated MAP kinase and
      the response was completely blocked by pretreatment of the Atg-/- cardiac
      myocytes with RX435. RX435 pretreatment greatly reduced stretch-induced
      activation of MAP kinase in Atg-/- cardiac myocytes. Interestingly, the same
      results were obtained in the cardiac myocytes of control mice. These results
      suggest that cytokine-gp130 may play a role in the stretch-induced MAP kinase
      activation independently of Ang II in cardiac myocytes.

PMID- 9588218
TI  - Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic
      changes.
AB  - An important prerequisite for a successful pregnancy is that the maternal immune
      system does not reject the fetus. Down-regulation of the T helper 1 (TH1)
      associated cellular immune response could therefore be essential. With flow
      cytometric techniques, we show on a single cell level that both CD4+ and CD8+ T
      cells from peripheral blood produce less TH1 cytokines (i.e. IFN-gamma and IL-2)
      and more TH2 cytokines (i.e. IL-4) during normal human pregnancy and shortly
      after delivery than during non-pregnancy. The TH1/TH2 cytokine ratio in T cells
      of women during pregnancy and after delivery was significantly decreased. In
      contrast the TH1/TH2 ratio was elevated to near normal in women with recurrent
      spontaneous abortions, indicating a marked shift towards TH1 immunity. Fas
      antigen (CD95) on T cells was significantly elevated during pregnancy and in the
      post-delivery phase whereas the intracellular expression of anti-apoptotic
      protein Bcl-2 remained unchanged. Nevertheless Fas-mediated apoptosis in T cells
      was markedly reduced during normal human pregnancy. We hypothesize that TH1 cells
      undergo predominantly Fas-mediated apoptosis during pregnancy as has been shown
      in some TH2-prone diseases (e.g. SLE, HIV) where an elevated Fas expression on
      peripheral T cells is observed. This could explain the exacerbated occurrence of
      TH2-associated diseases in pregnancy.

PMID- 9588219
TI  - EGF-dependent and independent programmed cell death pathways in NCI-H596 nonsmall
      cell lung cancer cells.
AB  - EGF receptor (EGFR) is a transmembrane glycoprotein with trosine kinase activity
      that is overexpressed in many human cancers, including lung. In the present
      study, we evaluated the effect of EGF and genistein, a tyrosine kinase inhibitor,
      on cell proliferation, EGFR phosphorylation and its downstream signal MAP kinase
      activation and investigated the involvement of these processes in programmed cell
      death in a human pulmonary adenosquamous carcinoma cell line, NCI-H596. Treatment
      with EGF resulted in phosphorylation of EGFR, activation of MAP kinase,
      phosphorylation of ERK 2 (an isoform of MAP kinase), increased cell proliferation
      and induction of cross-linked envelope (CLE) competence. Genistein abolished the
      ability of EGF to induce EGFR phosphorylation, to activate MAP kinase and to
      increase cell proliferation. Genistein alone stimulated CLE competence, but
      apparently by a different mechanism than EGF since genistein prevented EGF
      stimulated CLE competence. The genistein-stimulated CLE competence was
      accompanied by a decrease in cell proliferation and increased DNA fragmentation.
      These results demonstrate that genistein antagonizes growth stimulatory EGF
      signaling upstream of MAP kinase and may simultaneously stimulate an apoptotic
      pathway. Furthermore, EGF appears to stimulate an alternate, growth related
      programmed cell death pathway, not involving DNA fragmentation, but characterized
      by rapid proliferation and genistein-sensitive CLE competence.

PMID- 9588220
TI  - Re: letter to the editor regarding deposition of 3D structural studies of
      biological macromolecules.

PMID- 9588221
TI  - Excretion of sulfate and taurine in rats fed with a high protein diet.
AB  - Sulfate and taurine are the main metabolites of L-cysteine in mammals and are
      excreted in the urine. The effect of a high protein diet on the ratio of sulfate
      to taurine excretion was studied in rats using synthetic 25% (standard protein
      diet group, group A) and 40% (high protein diet group, group B) casein diets.
      Average taurine and sulfate excretions (mumol/kg of body weight per day) were
      280.4 +/- 93.8 and 943.2 +/- 144.8 in group A and 553.4 +/- 124.5 and 2675.0 +/-
      390.9 in group B, respectively. Thus, the average taurine/sulfate ratio in group
      A was 0.30 +/- 0.08. By a single administration of 5 mmol of L-cysteine/kg of
      body weight in group A, the average taurine and sulfate excretions increased to
      1127.5 +/- 120.2 and 4043.0 +/- 305.6, respectively, but the taurine/sulfate
      ratio changed only slightly (0.28). The average taurine/sulfate ratio in group B
      was 0.22 +/- 0.07, a significantly lower ratio than that in group A, which means
      that daily intake of a high protein diet resulted in more sulfate excretion. The
      taurine/sulfate ratio in group B was affected only slightly (0.19) by the
      cysteine administration as well. These results suggest that the ratio of taurine
      and sulfate production was determined by dietary protein content and that the
      increase in sulfate production is larger than that of taurine production when the
      intake of dietary protein is increased.

PMID- 9588222
TI  - Excretion of taurine and sulfate in rats fed with a low protein diet.
AB  - The effects of a low protein diet on the excretion of sulfate and taurine, major
      metabolites of L-cysteine in mammals, were studied in rats fed with synthetic 10%
      (group A) and 25% (group B) casein diets. The average excretions of total taurine
      (taurine plus hypotaurine) and total sulfate (free plus ester sulfate) (mumol/kg
      of body weight per day after the adaptation to the synthetic diet) in group A
      were 14.2 +/- 13.4 and 122.3 +/- 39.6, respectively, which were very low compared
      with 280.4 +/- 93.8 and 943.2 +/- 144.8, respectively, in group B. The
      taurine/sulfate ratio in group A was 0.12 +/- 0.11, which was significantly lower
      than that (0.30 +/- 0.08) in group B. A single intraperitoneal injection of 5
      mmol of L-cysteine per kg of body weight in group A resulted in an increase in
      average taurine and sulfate excretion to 693.4 +/- 195.6 and 2440.6 +/- 270.0,
      respectively, and thus the average taurine/sulfate ratio increased to 0.29. These
      increases were transient and low taurine excretion resumed again 24 h after the L
      cysteine administration. L-Cysteine injection in group B resulted in a similar
      increase in taurine and sulfate excretion, but the ratio changed only slightly
      (0.28). The present results suggest that in vivo production of taurine is reduced
      preferentially over sulfate production when sulfur amino acid supply is limited.

PMID- 9588223
TI  - Neonatal intrathymic splenocyte injection yields prolonged cardiac xenograft
      survival.
AB  - Intrathymic (i.t.) injection of allogenic cells without administration of anti
      lymphocyte serum (ALS) in neonatal recipients has induced donor-specific
      tolerance to subsequent cardiac allografts in rats. This study examines whether
      similar tactics can be successfully applied to a hamster-to-rat cardiac
      xenotransplantation model. Lewis neonates on their first day of life underwent
      i.t., subcutaneous (s.c.), intraperitoneal (i.p.), or intravenous (i.v.)
      injections of 5 x 10(7) Golden Syrian hamster splenocytes. After six weeks, the
      rats underwent heterotopic cardiac transplantation of hamster hearts.
      Cyclophosphamide (CyP) was administered on the day before surgery and
      postoperatively to suppress antibody-mediated graft rejection. Rats given
      splenocytes with 80 mg/kg of CyP had the following graft survival times: 8 to 12
      days for i.t. injection (mean, 9.4 days); 5 to 7 days for s.c. injection (mean,
      6.6 days); 4 to 11 days for i.p. injection (mean, 7.4 days); and 4 to 13 days for
      i.v. injection (mean, 7.9 days). Only the extension of graft survival produced by
      i.t. injection was statistically significant in comparison with the rats given
      only CyP treatment (mean, 7.5 days; P < 0.05). Thus, it appears that i.t.
      injection of xenogenic splenocytes in neonatal recipients with administration of
      CyP, but without ALS, can prolong xenograft survival. This biological
      intervention may be most useful in pediatric xenotransplantation when combined
      with other immunomodulation techniques.

PMID- 9588224
TI  - Effects of endoluminal stent-grafts on acute aortic dissection in dogs.
AB  - Acute aortic dissection is a life-threatening condition, and may be treated with
      aggressive hypotensive drug therapy, but emergency surgery is often necessary. We
      evaluated the effectiveness of stent-grafts for the treatment of acute aortic
      dissection. Aortic dissection was surgically created in the descending thoracic
      aorta in 20 adult mongrel dogs. A stent-graft was inserted in the entry position.
      The tested animals were divided into 4 groups based on re-entry type and blood
      pressure alteration rate (AR) after acute aortic dissection. After insertion of
      the stent, the following results were observed: a) AR improved; b) proximal
      descending aorta and superior mesenteric arterial flows increased; c) cardiac
      function improved; and d) the dissecting aortic diameter decreased in the
      presence of pressure gradient group. From these results, insertion of a stent
      graft to treat acute aortic dissection was judged to be effective.

PMID- 9588225
TI  - The usefulness of 99mTc-Technegas scintigraphy for diagnosing pulmonary
      impairment caused by pulmonary emphysema.
AB  - X-ray computed tomography (CT) has been used for diagnosis of pulmonary emphysema
      because it can reveal the morphology of low attenuation areas. Recently, 99mTc
      Technegas imaging, one of several types of scintigraphic techniques, has been
      used for ventilation scintigraphy. Technegas scintigraphy was performed on 15
      patients with pulmonary emphysema, and we compared the extent and degree of
      abnormal findings on Technegas scintigraphy with the extent of low attenuation
      areas shown by CT. We classified the findings of Technegas imaging into three
      grades, from mild to severe, according to the extent of peripheral irregularity
      and central hot spot formation. We also classified the findings of CT as
      centrilobular emphysema into three grades from mild to severe according to the
      extent of low attention areas in the peripheral lung fields. In 5 cases, CT and
      Technegas assessment resulted in equivalent diagnoses. In eight cases, Technegas
      images showed more detailed findings than CT images. In the two remaining cases,
      which were diagnosed as panlobular emphysema on CT, Technegas images showed the
      severe stage. Technegas scintigraphy was useful for diagnostic assessment of
      pulmonary emphysema, especially for panlobular emphysema, which is difficult to
      distinguish from the normal lung condition by CT assessment.

PMID- 9588226
TI  - Prognostic factors of small-cell lung cancer in Okayama Lung Cancer Study Group
      Trials.
AB  - In order to elucidate factors influencing the prognosis of small-cell lung cancer
      (SCLC), we reviewed the records of 253 patients with SCLC and evaluated 20
      pretreatment prognostic factors by univariate analysis and Cox's multiple
      regression analysis. Recursive partitioning and amalgamation (RPA) was employed
      to identify subgroups with similar survival rates. Cox's multiple regression
      analysis identified five significant factors: extent of disease, number of
      metastatic sites, serum albumin, serum lactate dehydrogenase, and presence of
      weight loss. Among these, extent of disease was the most influential factor. RPA
      analysis revealed three subgroups predicting significantly different prognoses.
      The median survival time and 3-year survival rate were 18.4 months and 20.6%,
      respectively for the good-risk group (limited disease without weight loss), 13.5
      months and 9.1%, respectively for the intermediate-risk group (limited disease
      with weight loss or extensive disease with less than two metastatic sites), and
      9.2 months and 0%, respectively for the poor-risk group (extensive disease with
      two or more metastatic sites). These results will be useful for development of
      new staging system or subsequent stratification for randomized trials.

PMID- 9588227
TI  - Relationship of serum markers of hepatitis B and C virus replication in
      coinfected patients.
AB  - To evaluate viral interference between hepatitis B and C, we studied coinfected
      patients serologically and molecular biologically. Twenty-seven patients positive
      for hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV)
      antibody, were classified into Groups BC-L and BC-H according to DNA-polymerase
      activity (less or greater than 100 cpm, respectively). Patients with hepatitis B
      or C alone were also enrolled as controls. HCV-RNA was detected more often in
      Group BC-L than in Group BC-H. Genotype 1b of HCV was determined in 75% of Group
      BC-H, 87.5% of Group BC-L, and 70.7% of hepatitis C-only patients. Activity of
      DNA-polymerase in coinfected patients was lower in patients positive for HCV-RNA
      as compared with those negative. HBsAg titers tended to be lower in coinfected
      patients than in patients with hepatitis B virus (HBV) alone. In conclusion, in
      coinfection, HBV may suppress the replication of HCV and HCV appears to reduce
      the expression of HBsAg and probably suppresses HBV replication.

PMID- 9588228
TI  - The usefulness of CYFRA 21-1 in diagnosing and monitoring malignant pleural
      mesothelioma.
AB  - Five patients with malignant pleural mesothelioma (MPM) were studied to determine
      whether CYFRA 21-1 is useful for diagnosis of this disease. In pleural effusions,
      the median concentration of CYFRA 21-1 from 4 patients with MPM was significantly
      higher than for 34 patients with benign diseases. The sensitivity of serum CYFRA
      21-1 for diagnosis of MPM was 40% and its concentration changed in proportion to
      disease activity in all cases. Immunohistochemically, anticytokeratin 19 antibody
      revealed strong staining in both epithelial and sarcomatous MPM tissues. Based on
      these results, we conclude that measurement of CYFRA 21-1 in pleural effusions
      and serum may be useful for diagnosing and monitoring MPM.

PMID- 9588229
TI  - Differential expression of systemic cytokine profiles in Chagas' disease is
      associated with endemicity of Trypanosoma cruzi infections.
AB  - Chagas' disease is a serious public health problem in Paraguay, however, the
      immunoepidemiology of the disease has not been well documented. A preliminary
      cross-sectional survey was carried out in two villages of the Paraguayan Chaco
      region and in five villages of the Oriental region to assess the endemicity of
      Trypanosoma cruzi infections. Thereafter, a subset of individuals (ages ranging
      from 23 to 65 years) participated in a follow-up study to evaluate clinical and
      parasitological parameters. Physical examinations and electrocardiograms (ECG)
      were conducted and blood samples collected for parasite detection and serology.
      The most frequent ECG abnormalities which were observed among chagasic
      individuals were left anterior hemifascicular block and right bundle branch
      block. Thirty-two of these subjects, seropositive and non-parasitemic from the
      high endemic Chaco (n = 16) and low endemic Oriental (n = 16) regions, were
      randomly selected for an analysis of T. cruzi-induced expression of cytokines IL
      2, IFN-gamma, IL-4 and IL-10 by RT-PCR. The individuals were grouped (n = 8)
      according to the presence or absence of abnormal ECG. In subjects that exhibited
      abnormal ECG profiles, five of eight (63%) individuals from the high endemic area
      showed a dominant type 2 (IL-4) response, whereas a comparable number (63%) of
      subjects from the low endemic area expressed a strong type 1 (IFN-gamma)
      response; the remainder (37%) presented a Th0-type (IFN-gamma, IL-4) response.
      Subjects with normal ECG showed a defined cytokine profile according to
      endemicity. All subjects from the high endemic region showed a Th0 response,
      whereas 100% of the individuals from the low endemic area demonstrated a type 1
      response. In most chagasic patients regardless of ECG profile and endemicity, IL
      2 expression was depressed, while IL-10 mRNA transcripts were consistently
      elevated. Taken together, these data indicate that chronic human chagasic disease
      is associated with increased systemic production of type 2 cytokines in response
      to T. cruzi infection and may be involved in the reciprocal down-regulation of IL
      2 production.

PMID- 9588230
TI  - Genetic relationships between Trypanosoma cruzi strains isolated from chronic
      chagasic patients in southern Brazil as revealed by RAPD and SSR-PCR analysis.
AB  - 30 Trypanosoma cruzi strains isolated from chronic chagasic patients were studied
      at the genotype level by RAPD with arbitrary primers and SSR-PCR analysis. The
      genetic distance of strains was measured by the percentage of unshared bands. The
      results showed that the strains isolated from chronic patients from different
      Chagas' disease endemic areas of Brazil constituted a broad group significantly
      more correlated than reported in previous studies, presenting RAPD profiles with
      an average of 71% of shared bands and SSR-PCR patterns with a mean of 59% of
      shared bands. In contrast to other findings in the literature, these strains did
      not group on the basis of their geographic origin. These results suggest that a
      special adaptation of a parasite population in human hosts from mixed infective
      T. cruzi populations circulating in nature may have occurred.

PMID- 9588231
TI  - In vitro growth inhibition of Plasmodium falciparum by retinol at concentrations
      present in normal human serum.
AB  - To assess the in vitro effect of retinol on Plasmodium falciparum, the standard
      isolates 3D7, D10, W2 and K1 in continuous culture were exposed to retinol added
      in concentrations ranging from 10(-7) to 0.1 mumol/l. Parasite growth inhibition
      was assessed from 3H-hypoxanthine incorporation. Triplicate experiments were
      performed at physiological pH and in the case of D10, additional experiments were
      performed at pH 7.2 and 7.6. Final media retinol concentrations were assayed
      using high performance liquid chromatography. Retinol inhibited growth of both
      asynchronous and synchronous cultures of 3D7 and D10 and asynchronous cultures of
      W2 and K1. IC50 values determined from assayed media concentrations ranged from
      0.2 to 3.9 mumol/l and were comparable to concentrations in normal human serum
      (1.0-3.0 mumol/l). IC50 values for asynchronous D10 cultures at pH 7.2 were lower
      than at pH 7.4 or 7.6 (0.5, 3.9 and 5.0 mumol/l, respectively); results from
      synchronous cultures were similar. These data suggest that P. falciparum is a
      retinol-sensitive parasite, especially at pH levels equivalent to those in an
      acidotic patient. Adjunctive retinol therapy may have a role in clinical
      management of malaria.

PMID- 9588232
TI  - Estimated persistence of anti-HAV antibodies after single dose and booster
      hepatitis A vaccination (0-6 schedule).
AB  - The persistence of antibodies after a single dose and booster vaccination against
      hepatitis A (Havrix 1440) has not yet been assessed. By reanalysing previously
      published data of serum titres and application of a two-component model, we
      estimated the duration of protection. In 134 vaccinees, aged 20-39 years, the GMT
      1 month after booster was 3629 mlU/ml, which would result in an estimated
      duration of protection of 34.5 years and in 66 vaccinees aged 40-62 years a GMT
      of 2320 mlU/ml was calculated, resulting in a duration of protection of 31.5
      years. Even when taking the minimum observed titres in the older age group into
      account, the duration of protection will be more than 10 years. Considering at
      the same time, its good tolerability and compliance, the single dose hepatitis A
      vaccination appears highly recommendable in travel medicine.

PMID- 9588233
TI  - Helminth associated hypereosinophilia and tropical endomyocardial fibrosis (EMF)
      in Nigeria.
AB  - There should be a recognisable trend between the incidence of hypereosinophilia
      and the duration of tropical endomyocardial fibrosis (EMF), if the hypothesis,
      that EMF is the burnt out phase of eosinophil associated heart disease, is
      correct. We tested this hypothesis in a prospective study of 89 consecutive EMF
      cases over an 18 year period at two Nigerian locations (Ife in South West and
      Calabar in South East). We carefully dated the duration of EMF symptoms at first
      presentation and screened for hypereosinophilia (eosinophilia > or = 1500/mm3),
      and their causes. When no cause was identified for hypereosinophilia we gave a
      therapeutic trial with diethylcarbamazine to the patients. An eosinophil count >
      or = 1000/mm3 was recorded in 80% of 24 cases seen within 6 months; 55% of 46
      cases seen 0-24 months; 54% of 18 cases seen 25-48 months and 21% of 25 cases
      seen more than 49 months of onset of symptoms: while the respective distribution
      of eosinophil count > or = 1500/mm3 for similar periods were 66, 44, 27 and 21%.
      This reflects a highly significant (P < 0.001) inverse relationship between
      hypereosinophilia and the duration of EMF and strengthens the concept that EMF
      (without eosinophilia) represents the late stage of eosinophilic heart disease.
      The localisation of endemic EMF to the low-lying tropical rain forest Zone and
      its predominant occurrence among rural dwellers and farmers suggest a vector
      borne etiologic agent. Microfilaria was the most likely cause of
      hypereosinophilia in the cases presented.

PMID- 9588234
TI  - Prevalence of taeniasis and cysticercosis in a population of urban residence in
      Honduras.
AB  - To determine the prevalence of antibodies to Taenia solium and taeniasis in a
      population of urban residence, an epidemiological study was carried out in a
      military institution located in Tegucigalpa, the capital city of Honduras. A
      total of 404 persons were interviewed to collect epidemiological data,
      investigate antibodies to T. solium cysticercus by the enzyme-linked
      immunoelectrotransfer blot (EITB) assay and taeniasis by Ritchie's concentration
      technique. A total of 41 persons that were living at the headquarters and were
      traveling frequently to their rural hometowns were regarded as rural residents,
      the remaining 363 persons were considered urban residents. The seroprevalence of
      antibodies was 22% (9/41) in the rural residents and 15% (54/363) in the urban
      residents. The overall seroprevalence was 15.6% (63/404). Analyses of risk
      factors for seropositivity in the urban residents showed that seropositivity was
      statistically associated with poor household conditions such as raising pigs
      (odds ratio (OR), 5.39; 95% confidence interval (CI), 1.42-19.50), lack of
      potable water (OR, 3.66; CI, 1.25-9.94), lack of sanitary toilet (OR, 2.92; CI,
      1.35-6.05) and earthen floor (OR, 2.48; CI, 1.28-4.73). Also seropositivity was
      associated with low academic education (OR, 2.5O; CI, 1.33-4.69) and lack of
      knowledge about the parasite (OR, 2.39; CI, 1.26-4.49). Out of 328 persons
      examined for intestinal parasites, two soldiers (0.6%) coming from rural areas
      were identified as Taenia sp. carriers. T. solium was identified in one case.
      Although T. solium infections originate and are more prevalent in rural villages,
      the high seroprevalence found in this study indicates that they can also be found
      at important levels in urban communities. Migration of tapeworm carriers from
      rural areas to the city grants the transmission of cysticercosis when poor
      environmental and social conditions are present.

PMID- 9588235
TI  - A semi-quantitative ELISA for detection of Trypanosoma brucei gambiense specific
      antibodies in serum and cerebrospinal fluid of sleeping sickness patients.
AB  - A semi-quantitative ELISA, using variable surface glycoprotein of T.b. gambiense
      as antigen, was developed for the detection of antibodies of different
      immunoglobulin isotypes in serum and cerebrospinal fluid of sleeping sickness
      patients. Using the assay, the antibody profiles of paired serum and
      cerebrospinal fluid samples of 28 patients have been studied. Total
      concentrations of various Ig isotypes were determined as well. In serum and
      cerebrospinal fluid a drastic increase in IgG, basically IgG1, as well as in IgM
      levels was observed. The concentration of IgA remained relatively normal. The
      antitrypanosomal antibodies detected in serum and cerebrospinal fluid were mainly
      of the IgG (IgG1 and IgG3) and IgM isotypes. Measurement of immunoglobulin and
      trypanosome specific antibody concentrations in serum and CSF allows calculation
      of intrathecal antibody synthesis and is a possible tool for determining the
      clinical stage of sleeping sickness.

PMID- 9588236
TI  - The early diagnosis of typhoid fever prior to the Widal test and bacteriological
      culture results.
AB  - In an attempt to evaluate various clinical and laboratory features available
      within 24 h of admission, prior to the Widal test and bacteriological culture
      results as potential diagnostic aids in typhoid fever, we undertook a
      retrospective unit-based case control study in 90 febrile adult and paediatric
      patients admitted to King Edward VIII Hospital, Durban, South Africa with an
      initial diagnosis of typhoid fever. A total of 30 blood culture-proven typhoid
      fever patients (cases) were matched to 60 patients confirmed as not having
      typhoid fever (controls) by age, sex, race and severity of illness on admission.
      Features significantly associated with a final diagnosis of typhoid fever were: a
      pre-admission duration of fever > or = 7 days (odds ratio (OR) 6.9); hepatomegaly
      (OR 3.2); a normal leucocyte count (OR 10.8); a leucocyte count of < 10.0 x
      10(3)/mm3 (OR 30.2); and leucopenia due to absolute neutropenia with a relative
      lymphocytosis (OR 11.8). Although the sensitivity, specificity and predictive
      values of any of these features cannot be used reliably to distinguish typhoid
      fever from other non-typhoidal febrile illness, it is concluded that leucopenia
      due to absolute neutropenia with relative lymphocytosis, when present, is highly
      suggestive of typhoid fever. A leucocyte count of > 10.0 x 10(3)/mm3 (OR 0.03)
      provides strong presumptive evidence against such a diagnosis.

PMID- 9588237
TI  - Genetic markers for strongylid nematodes of livestock defined by PCR-based
      restriction analysis of spacer rDNA.
AB  - Twenty-four species of parasitic nematode (order Strongylida) from sheep, goats,
      cattle or pigs were characterised using a polymerase chain reaction-linked
      restriction fragment length polymorphism technique (PCR-RFLP). The ribosomal
      (r)DNA region spanning the first internal transcribed spacer (ITS-1), 5.8S rRNA
      gene and the second internal transcribed spacer (ITS-2) (designated ITS) was
      amplified from genomic DNA by polymerase chain reaction (PCR), digested
      separately with four restriction endonucleases (RsaI, HinfI, DraI or NlaIII) and
      the fragments separated by agarose gel electrophoresis. The PCR products
      amplified from all species appeared as a single band of approximately 870 bp in
      size, except for Ostertagia ostertagi whose product was approximately 1250 bp.
      The PCR-RFLP analysis of ITS revealed characteristic restriction patterns for all
      species, except for C. surnabada and C. oncophora which had identical patterns.
      The study demonstrated that ITS contains useful genetic markers for the
      identification of a range of strongylid nematodes of livestock. These markers
      should be of use in specific PCR assays for the identification of developmental
      stages of the parasites where morphological characters are unreliable.

PMID- 9588238
TI  - Differential sensitivity of New World Leishmania spp. promastigotes to complement
      mediated lysis: correlation with the expression of three parasite polypeptides.
AB  - American tegumentary leishmaniasis is caused by Leishmania of the subgenera
      Leishmania and Viannia. In this paper, we demonstrate that promastigotes of these
      two subgenera display distinct characteristic patterns of complement sensitivity
      during growth in vitro. Using fresh normal human serum in lytic assays, we show
      that while promastigotes of two species of the subgenus Leishmania differentiate
      into forms that are more resistant to the lytic action of complement,
      promastigotes of three species of the subgenus Viannia remain sensitive to
      complement mediated lysis during all stages of their growth in vitro. Complement
      resistance of the subgenus Leishmania is temporary, reaching its peak at the
      beginning of the stationary phase of growth, and decreasing thereafter. By sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) we detected in L.
      amazonensis (subgenus Leishmania), but not in L. guyanensis (subgenus Viannia),
      three polypeptides whose expression parallels the resistance of promastigotes to
      complement-mediated lysis.

PMID- 9588239
TI  - Resistance to benzimidazoles and levamisole in nematode parasites of sheep in
      Nyandarua District of Kenya.
AB  - The occurrence of anthelmintic resistance on 25 sheep farms in the Nyandarua
      District of Kenya was investigated, using the faecal egg count reduction test
      (FECRT), the egg hatch assay (EHA) and a larval development assay (LDA). In the
      FECRT, resistance to both benzimidazoles (BZs) and levamisole (LEV) was detected
      on four farms, resistance to LEV only on three farms and to BZs, only on two
      farms. Haemonchus contortus was the predominant nematode species in both pre
      treatment and post-treatment faecal cultures. Out of the six farms where BZ
      resistance was detected in the FECRT, only isolates from one farm had an LD50
      value higher than 0.5 microM thiabendazole (TBZ) (0.1 microgram TBZ/ml) in the
      EHA indicating resistance. Isolates from three other farms, where susceptibility
      to BZs was detected and four with suspected BZ resistance in the FECRT, had LD50
      values higher than 0.5 microM TBZ in the EHA. The LD50 values for TBZ in the LDA
      for four of the six isolates with BZ resistance in the FECRT were higher than 0.5
      microM (0.59-2.07) TBZ. There were disagreements in ascribing resistance for
      various farms, between methods of calculating and interpreting the faecal egg
      count reduction percentages (FECR%) based on the arithmetic mean, and those where
      the geometric mean eggs per gram (EPG) of faeces are used. Inclusion of pre
      treatment EPG or control group EPG in the calculation of FECR% resulted in
      similar variations.

PMID- 9588241
TI  - Evaluation of three methods to control Bulinus truncatus, the intermediate host
      of Schistosoma haematobium in an irrigation scheme, Tessaout-Amont, Morocco.
AB  - In Morocco, the implementation of new irrigation schemes resulted in the
      introduction of schistosomiasis haematobium to new areas. Canal structures
      (especially syphon boxes) were found to be favourable habitats for Bulinus
      truncatus and they constitute important transmission sites. Three methods for
      snail control in these syphon boxes were assessed in the Tessaout-Amont
      irrigation scheme. Molluscicide (niclosamide) application resulted in a
      pronounced reduction in the snail population density, but snails started to
      recolonise the sites a few months later. Regular brushing of the inner sides of
      the syphon boxes and covering the syphon boxes, so as to exclude light, resulted
      in significant reductions in snail numbers. However, the latter methods were not
      as efficient as the molluscicide.

PMID- 9588240
TI  - Detection of Leishmania (Viannia) braziliensis complex in wild mammals from
      Colombian coffee plantations by PCR and DNA hybridization.
AB  - The small mammal fauna of coffee plantations in SW Colombia was surveyed to
      determine which of the species present were infected with parasites of the
      Leishmania (Viannia) braziliensis complex and might therefore act as reservoirs
      of human cutaneous leishmaniasis. Fifty animals of seven different species were
      captured. Tissue samples were taken from the ears of specimens from each of the
      seven species. Thirty three samples were analysed by polymerase chain reaction
      (PCR) using oligonucleotide primers directed against conserved regions of L. (V)
      braziliensis complex kinetoplast DNA. Three of the samples (two from mouse
      opossums Micoureus demerarae, and one from a pygmy rice at Microryzomys minutus)
      gave positive results based on PCR analysis. When the samples were subjected to
      DNA hybridization (dot blot) analysis using the B18 (L. (V.) braziliensis complex
      specific) probe, a total of ten specimens belonging to six species (the opossums
      M. demerarae and Didelphis marsupilalis, the rodents Melanomys caliginosus, Mi.
      minutus and Rattus rattus, and a rabbit Sylvilagus brasiliensis) gave positive
      results, indicating that all these animals had flies of species occurring in the
      same habitat by allowing them to feed on infected animals.

PMID- 9588242
TI  - Serum liver enzymes profile of Wistar rats following chronic consumption of fresh
      or oxidized palm oil diets.
AB  - The effect of chronic consumption of palm oil diets on serum levels of some liver
      enzymes in rat was investigated. Two groups of rats were fed on either fresh or
      thermally oxidized palm oil, mixed at 15% level for 18 weeks and their effects on
      serum levels of alkaline phosphatase (EC 3.1.3.1), aspartate aminotransferase (EC
      2.6.1.1) and alanine aminotransferase (EC 2.6.1.2) enzymes were compared with a
      control group receiving normal rat feed. The levels of alkaline phosphatase (ALP)
      in the two groups were significantly higher (P < 0.05-0.01) than control. Mean
      ALP levels were significantly different in the two test groups (P < 0.05).
      Similarly, there was significant elevation (P < 0.05-0.01) of aspartate
      aminotransferase (AST) levels in oxidized oil-fed and fresh oil-fed groups when
      compared with the control. The mean alanine aminotransferase (ALT) level was
      significantly higher (P < 0.01) in the oxidized oil-fed group than the control
      and fresh oil-fed groups. The results indicate that chronic consumption of
      thermoxidized palm oil, with its accompanying hazardous free radicals, may be
      more injurious to liver cell integrity than fresh palm oil.

PMID- 9588244
TI  - Hydroxyurea marketed for sickle cell anemia.

PMID- 9588243
TI  - Cohort study on canine emigration and Leishmania infection in an endemic area for
      American visceral leishmaniasis. Implications for the disease control.
AB  - American visceral leishmaniasis is a main public health matter in Brazil. Since
      dogs have been incriminated as the main urban reservoir of AVL agent Leishmania
      chagasi, a cohort study aimed at understanding the dynamics of the canine
      infection was carried out in Jequie--an endemic community in the Northeast of
      Brazil. The inhabited urban and periurban areas of Jequie were divided into 140
      clusters of 0.25 km2. All 1681 dogs domiciled in 34 randomly selected clusters
      were screened for Leishmania antibodies in an enzyme-linked immunosorbent assay.
      After the seropositive dogs were painlessly eliminated, a cohort of 1286
      seronegative dogs was followed up for 18 months, yielding a total of 1739.7 dog
      years. The overall incidence of Leishmania infection, as assessed by the
      detection of Leishmania antibodies in blood samples collected every six months,
      was 6.55 cases/100 dog-years (95% confidence interval; CI 6.04-7.26). Two subsets
      of clusters, with 0.70 and 1.35 relative risks of infection, were identified. The
      annual emigration rate was 2.26 cases/100 dog-years (95% CI 1.86-2.66). The
      implications of these findings for the control of American visceral leishmaniasis
      are discussed.

PMID- 9588245
TI  - New guidelines target sexually transmitted diseases.

PMID- 9588246
TI  - Studies support use of omeprazole for NSAID-induced ulcers.

PMID- 9588247
TI  - Lowering the risk of esophagitis from alendronate therapy.

PMID- 9588248
TI  - Confidentiality of patient records.

PMID- 9588249
TI  - Human gene therapy for hereditary diseases: a review of trials.
AB  - Human gene therapy trials directed at hereditary diseases, including adenosine
      deaminase (ADA) deficiency, familial hypercholesterolemia, and cystic fibrosis,
      are reviewed. Human gene therapy involves the introduction and expression of
      recombinant genes in somatic, nonreproductive cells with the intent to reverse or
      prevent a particular disease. Two methods for introducing genes into human cells
      are currently being used in clinical trials. Ex vivo gene delivery involves
      removing targeted cells from the patient's body, introducing the recombinant gene
      into the cells, and placing the modified cells back into the patient's body. In
      vivo gene delivery involves placing the recombinant gene directly into the
      patient's body, targeting the tissue or cell of interest. The transfer of the
      recombinant gene into the cell and the subsequent expression of the transgene
      product are the rate-limiting steps for successful gene therapy. A variety of
      methods, including the use of modified viruses and synthetic vectors, are
      currently being used in clinical trials. Since the approval and initiation of the
      first human gene therapy trial to treat ADA deficiency in 1989, there have been
      more than 170 approved gene therapy trials in the United States. More than 1500
      patients have been enrolled in human gene therapy trials worldwide. Preliminary
      clinical trials have targeted diseases such as ADA deficiency, familial
      hypercholesterolemia, and cystic fibrosis. These trials have employed variable
      designs and strategies, making interpretation of the results difficult. However,
      the initial data are encouraging, and the procedures have been well tolerated.
      The clinical utility of human gene therapy remains to be defined; immediate
      efforts will focus on improving vector design to limit toxicity and enhance the
      efficiency of gene transfer.

PMID- 9588250
TI  - Troglitazone: an antidiabetic agent.
AB  - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and
      dosage and administration of troglitazone are reviewed. Troglitazone is the first
      oral thiazolidinedione approved for use in treating non-insulin-dependent
      diabetes mellitus (NIDDM). The drug's mechanism of action has not been fully
      elucidated. Troglitazone acts as an insulin sensitizer. Cell-line and animal
      models indicate that troglitazone may decrease hepatic glucose output by
      decreasing the rate of gluconeogenesis in the liver or by increasing glycolysis.
      Troglitazone is rapidly absorbed after oral administration, with peak
      concentration occurring in two to three hours. Food increases absorption by 30
      85%. The drug is extensively metabolized in the liver. Troglitazone has been
      shown to be efficacious in treating NIDDM, both as monotherapy and in combination
      with oral sulfonylureas. Patients who are obese or who have high fasting plasma
      insulin levels may derive the greatest benefit. Patients with impaired glucose
      tolerance, syndrome X, polycystic ovary syndrome, gestational diabetes, or
      Werner's syndrome may also benefit from troglitazone. Adverse effects, including
      hematologic abnormalities, liver toxicity, and hypoglycemia, have been rare in
      published trials; no life-threatening effects have been reported thus far. The
      recommended initial dosage is 200 mg once daily with meals, with an increase to
      400 mg daily if satisfactory glycemic control is not achieved after two to four
      weeks. The average wholesale price is $348 for 100 200-mg tablets and $534 for
      100 400-mg tablets. Troglitazone may be an effective agent for treating NIDDM,
      especially in patients who are obese or who have high fasting plasma insulin
      levels.

PMID- 9588251
TI  - Stability of mycophenolate mofetil in an extemporaneously compounded oral liquid.
AB  - The stability of mycophenolate mofetil in an extemporaneously prepared 100-mg/mL
      oral liquid was studied. The contents of 80 250-mg capsules of mycophenolate
      mofetil were combined with sterile water for irrigation and cherry-flavored syrup
      to produce 200 mL of suspension. Six 1-mL samples were analyzed immediately, and
      the rest of the suspension was poured into 12 2-oz amber polyethylene
      terephthalate [corrected] G(PETG) bottles; six bottles were stored at 23-25
      degrees C and six at 2-8 degrees C. Samples were removed on days 14, 21, 28, 35,
      49, 63, 92, and 121 for analysis by high-performance liquid chromatography; pH
      was measured initially and at each sampling time. The pH of the suspension was
      initially 6.1 and remained unchanged throughout the study. The suspension
      retained more than 90% of its initial drug concentration for 121 days at 23-25
      and 2-8 degrees C. There was no detectable change in color or odor and no visible
      microbial growth in any sample. Mycophenolate mofetil in a 100-mg/mL oral liquid
      prepared with cherry-flavored vehicle and stored in amber PETG bottles was stable
      for 121 days at 23-25 and 2-8 degrees C.

PMID- 9588252
TI  - Use of intravenous inotropic therapy in the home.
AB  - The role of home i.v. inotropic therapy in managing patients with refractory
      congestive heart failure (CHF) is reviewed. CHF is a fairly common health care
      problem in the United States and is associated with significant morbidity and
      mortality. Although several oral medications are used to treat CHF, individuals
      with New York Heart Association class III or IV disease may require i.v.
      inotropic therapy. Typically, these patients are managed in the hospital.
      However, some patients dependent on i.v. therapy may be safely treated at home.
      While the functional status and quality of life of these individuals may be
      improved, there is no evidence that home i.v. inotropic therapy increases their
      overall survival. Dobutamine is currently the preferred i.v. inotropic agent, but
      amrinone and milrinone are suitable alternatives. Although tolerance to
      dobutamine may develop with continuous drug administration, intermittent therapy
      has been associated with an increased risk of sudden death. The optimal infusion
      schedules for amrinone and milrinone have not been clearly established. Home i.v.
      inotropic therapy may improve the quality of life in carefully selected patients
      with refractory CHF.

PMID- 9588253
TI  - Using process control charts to monitor dispensing and checking errors.

PMID- 9588254
TI  - HIV pharmacotherapy clinic.

PMID- 9588255
TI  - Sheath for disposable syringes.

PMID- 9588256
TI  - Nationally speaking. The genius within.

PMID- 9588257
TI  - Occupation in lifestyle redesign: the Well Elderly Study Occupational Therapy
      Program.
AB  - This article describes an innovative preventive occupational therapy intervention
      for well older adults, the Well Elderly Treatment Program. In a previously
      reported large-scale randomized effectiveness study, this intervention was found
      to be highly successful in enhancing the physical and mental health, occupational
      functioning, and life satisfaction of multicultural, community-dwelling elders.
      In this article, the philosophical background, manner of development, topical
      content, methods of program delivery, and mechanisms underlying the program's
      positive effects are discussed, along with implications for occupational therapy
      practice. The treatment was based on application of occupational science theory
      and research and emphasized the therapeutic process of lifestyle redesign in
      enabling the participants to actively and strategically select an individualized
      pattern of personally satisfying and health-promoting occupations. The wide
      ranging effectiveness of the program supports the occupational therapy
      profession's emphasis on occupation in affecting health and positions
      practitioners to extend their services to the realm of preventive interventions.

PMID- 9588258
TI  - Occupation-centered assessment of children.
AB  - The past 5 years have seen increasing calls to reexamine our assessment and
      intervention practices to ensure that they reflect the profession's basic focus
      on occupation. Although a number of noteworthy efforts in this direction have
      been presented for adult practice areas, implementation of occupation-centered
      assessment in pediatric has been hampered by the lack of a consistent framework
      to guide this process. This article will present an adaptation of the functional
      assessment model proposed by Trombly (1993) designed to better reflect the unique
      needs and situations of children. It is a multilevel model that examines the
      pattern of a child's occupations in a particular environment as well as the
      performance of important tasks and activities that are part of these occupations.
      It is proposed that this model can serve as an organizing framework for an
      occupation-centered assessment process by helping to identify the critical
      questions that need to be addressed at each level of analysis and the kinds of
      measures that might be used to obtain relevant information. The newly completed
      School Function Assessment will be used to illustrate application of the
      framework to examine occupational performance of children in elementary school.

PMID- 9588259
TI  - Meaning and misunderstanding in occupational forms: a study of therapeutic goal
      setting.
AB  - OBJECTIVE: This study examined occupational therapists' use of the occupational
      form of goal setting as therapy and its impact on clients. METHOD: The study
      method was qualitative, using participant observation and interviewing as the
      main source of data. RESULTS: The findings illustrated that therapists work both
      to give substance to the occupational form and to create the context of an
      implied narrative that imbues it with particular meanings. Simultaneously,
      clients' experience of meaning is influenced by a personal volitional narrative.
      When the two narratives do not coincide, therapists' efforts to maintain the
      occupational form intensify as they encourage clients toward attitudes and
      performances that do not resonate with the clients' experience of reality.
      CONCLUSION: The findings underscore the importance of recognizing that
      occupational forms are embedded in social processes and perspectives that
      inevitably come into play when occupational forms are used as therapy.

PMID- 9588260
TI  - Putting occupation into practice: occupation as ends, occupation as means.
AB  - This article addresses a difficulty that many occupational therapists experience:
      maintaining occupation as the core of their therapeutic intervention. This
      difficulty not only results from but also contributes to occupational therapy's
      struggle with professional identity. Current manifestations of the problem are
      described as component-driven practice and the narrowing of occupation to basic
      activities of daily living. The concepts of occupation as ends and occupation as
      means are proposed as a practical solution to guide treatment planning and merge
      remediation and adaptation within a single occupational session. Each concept is
      investigated in terms of its history within the profession and its usefulness for
      analyzing and solving therapeutic problems. These concepts are discussed as
      useful guidelines to help occupational therapists not only in their clinical
      decision making but also in their understanding and expression of the field's
      unique expertise. A case example, applying occupation as ends and occupation as
      means to evaluation and treatment, is presented.

PMID- 9588261
TI  - Occupation: the keystone of a curriculum for a self-defined profession.
AB  - The idea of occupation is proposed as the basis for constructing a curricular
      renaissance for occupational therapy in preparation for a new millennium.
      Implementing an occupation-centered curriculum could create a more integrated
      profession in which practice, ideas, scholarship, and education nurture and
      support one another, increasing the autonomy of both the occupational therapy
      profession and recipients of its services. A practice-oriented rationale for
      curricular design includes explication of the idea of occupation, a view of the
      person as an occupational being embedded in that concept, and the thought process
      of occupational therapy. Recommendations are provided to create an integrated
      curriculum that will contribute to future-oriented practice and a self-defined
      profession.

PMID- 9588262
TI  - Occupational therapy and rehabilitation: an awkward alliance.
AB  - This article argues that although occupational therapy and rehabilitation are
      often considered synonymous, the latter is but one aspect of the former. Early
      influences on occupational therapy are briefly reviewed, and some philosophical
      ideas about activity are described. The rationale for the use of occupations as
      treatment in the early part of this century, both in Canada and in the United
      States, is examined and contrasted with the development of physical medicine and
      rehabilitation after World War II. This discussion demonstrates that the origins
      of occupational therapy and rehabilitation in North America had little in common.
      As occupational therapy became incorporated into rehabilitation, the profession's
      core values eroded, and although current definitions of rehabilitation offer a
      more appropriate fit for occupational therapy, rehabilitation continues to see
      engagement in occupations as a separate and subsequent step. The article
      concludes by considering future directions and the tasks that lie ahead.

PMID- 9588263
TI  - Occupation-centered practice in hand rehabilitation using the experience sampling
      method.

PMID- 9588264
TI  - How can the academic culture move toward occupation-centered education?

PMID- 9588265
TI  - Development of rheumatology in Singapore.

PMID- 9588266
TI  - Ankylosing spondylitis in Singapore: a study of 150 patients and a local update.
AB  - This paper presents the results of a clinical study of 150 patients in Singapore
      with ankylosing spondylitis (AS) and reviews recent developments locally with
      regards to the disease. The patients were predominantly males (ratio 7:1) and
      Chinese (n = 147). The onset of disease is usually in the early twenties and
      there was a mean delay of 6.3 years before diagnosis was made. Peripheral joint
      involvement is common but apart from uveitis (17%), extra-articular
      manifestations are rare. AS patients have abnormal lipid profiles and lower bone
      mineral density compared to healthy controls. HLA*B2704 is the predominant
      subtype in our Chinese patients whilst HLA*B2706 was found only in healthy
      controls. Intensive group physiotherapy is beneficial for patients with
      spondyloarthropathy.

PMID- 9588267
TI  - Clinical presentation and disease associations of gout: a hospital-based study of
      100 patients in Singapore.
AB  - The aim of this retrospective study was to characterise the clinical presentation
      and disease associations of Oriental patients with gout seen in our hospital over
      a six-month period. One hundred patients comprising of 77 males and 23 females
      [89% Chinese, 7% Malays, 2% Indians and 2% others; mean age was 50.9 years (range
      18 to 82 years), mean age at onset of disease was 43.7 years (range 16 to 78
      years)] were studied. The disease was familial in 18% and 44% of patients had a
      history of alcohol ingestion. Co-morbid conditions included hypertension (36%),
      hyperlipidaemia (25%), renal failure (17%), ischaemic heart disease (13%),
      diabetes mellitus (4%), systemic lupus erythematosus (3%), psoriasis (2%) and
      ankylosing spondylitis (1%). The majority of patients (68%) had at least one
      associated disease. At the onset of disease, the joints commonly involved were
      the ankles (39%) and knees (27%) whilst the first metatarsophalangeal (MTP) joint
      was affected in only 26% of cases. Polyarticular onset was uncommon (n = 6). The
      precipitating factors reported by the patients included food (n = 23), alcohol (n
      = 12), drugs (n = 4), trauma (n = 3) and surgery (n = 2). Eleven patients had a
      history of renal calculi and 15% had tophaceous gout. Majority of patients (71%)
      had been treated with urate-lowering drugs (allopurinol). We concluded that gout
      in Singapore predominantly affects middle-aged men who often have an accompanying
      illness.

PMID- 9588268
TI  - Adult-onset Still's disease in an oriental population: manifestations, course and
      outcome in 16 patients.
AB  - This retrospective descriptive study aims to characterise and compare the
      clinical manifestations, course and outcome of 16 Oriental patients with adult
      onset Still's disease diagnosed in the last 4 years with published data based on
      Western populations and another Oriental (Japanese) series. Like the Japanese, we
      found a female preponderance, an older age at onset, and fewer patients with
      abdominal pain, myalgia, sore throat and serositis compared to the Western
      series. A longer delay in diagnosis occurred in patients lacking either arthritis
      or rash at presentation. Most patients had mild hyponatraemia and 2 patients had
      overt syndrome of inappropriate anti-diuretic hormone secretion. All patients
      showed a dissociation of elevated aldolase with normal to low creatine kinase
      levels. Over 50% relapsed within a year from diagnosis and needed slow-acting
      anti-rheumatic drugs as steroid-sparing agents. Two were given intravenous pulse
      cyclophosphamide therapy for progressive pneumonitis. Outcome was generally good
      with minimal functional impairment and no mortality.

PMID- 9588270
TI  - The sensitivity and specificity of autoantibodies to the Sm antigen in the
      diagnosis of systemic lupus erythematosus.
AB  - The anti-Sm test is thought to be specific for the diagnosis of systemic lupus
      erythematosus (SLE) and is one of the American College for Rheumatology (ACR)
      criteria for the classification of SLE. Locally, the sensitivity and specificity
      of this test for the diagnosis of SLE are unknown. We therefore aim to study the
      sensitivity and specificity of this test in our local context. A total of 1034
      patient samples that were sent for routine testing of anti-Sm antibodies over a
      30-month period, were included in the study. However, only 1031 patient samples
      were included in the final analysis as 3 casenotes were not traceable. Clinical
      diagnoses were obtained through a lupus database and chart review. Quantification
      of the anti-Sm antibodies was by the enzyme-linked immunosorbent assay (ELISA)
      technique. Positive anti-Sm test results were present in 165 samples, comprising
      156 (94.5%) samples from lupus patients and 9 (5.5%) having diagnoses other than
      SLE. These diagnoses ranged from arthritis, overlap syndrome, Raynaud's
      phenomenon and cardiac-related diseases. The calculated sensitivity and
      specificity of the anti-Sm test, using a positive cut-off value of 20 units/ml,
      were 39.7% and 98.6%, respectively. If the positive cut-off value is raised to 30
      units/ml, the specificity rises marginally to 99.5% but the sensitivity will drop
      by more than 10 percentage points to 27.2%. The anti-Sm test is not useful as a
      screening test for lupus but a positive result is highly specific for SLE.

PMID- 9588269
TI  - Clinical predictors of nephritis in systemic lupus erythematosus.
AB  - We identified clinical predictors of lupus nephritis presenting more than 6
      months after the diagnosis of lupus in a cohort of 335 lupus patients. Almost 24%
      (80/335) of patients developed nephritis more than 6 months after the diagnosis
      of lupus. Using a Cox proportional hazards model, we found hypertension,
      thrombocytopaenia and leukopaenia to be associated with lupus nephritis
      presenting more than 6 months after diagnosis, with adjusted relative risks of
      2.5 (95% CI 1.3 to 4.7), 4.3 (95% CI 1.7 to 10.8) and 3.2 (95% CI 1.7 to 6.2)
      respectively. In this cohort, hypertension, thrombocytopaenia and leukopaenia
      were associated with lupus nephritis presenting more than 6 months after the
      diagnosis of lupus.

PMID- 9588271
TI  - Education in rheumatology.
AB  - The increasing burden of arthritis and musculoskeletal conditions in both
      developed and developing societies is shown by national and community-based
      surveys. Many complaints are sufficiently severe to cause disability and loss of
      time from work. Medical care is provided most often by primary health care
      physicians who are often inadequately trained to handle these conditions. Better
      medical student education that focuses on common community problems remains
      crucial. Strong rheumatology units with a commitment to teaching and research are
      necessary to redress any imbalance as new curricula are developed. Such units
      also have to take responsibility for primary health care physician and nurse
      education in how to manage common musculoskeletal problems. Arthritis Foundations
      and patient support groups have a role in public education and in increasing
      community knowledge on the causes and prevention of some common conditions so as
      to assist in improving overall care. New initiatives in professional and public
      education have given encouraging results, but further changes in community
      attitudes and perceptions of chronic conditions are necessary and are within the
      scope of most Arthritis Foundations' key objectives.

PMID- 9588272
TI  - Murine lupus: pathogenic mechanisms and genetic origins.
AB  - Research in several murine models of lupus, reinforced with patient studies, has
      served to identify key events leading to lupus nephritis. Among these, anti
      nuclear antibody (ANA) induced end-organ damage, production of such ANAs by
      intrinsically hyperactive B-cells, and antigen-specific, cognate T-cell help have
      been well documented. Though studies in parallel fields of immunology have
      uncovered a plethora of molecular defects that can potentially drive these key
      pathogenic events, the actual molecular defects that are responsible for these
      events in spontaneous lupus remain unknown. Whereas genetically pre-determined
      triggers are most likely responsible for each of these pathogenic events, humoral
      and environmental triggers are likely to exert secondary effects, in attenuating
      or accentuating these mechanisms. Recent genetic studies in mice have allowed
      researchers to dissect this complex autoimmune disease into a collection of
      simpler immunological aberrations. These simpler murine models will facilitate
      the identification and characterization of the fundamental building blocks of
      lupus, and advance our understanding of the genetics and pathology of this
      intriguing disease.

PMID- 9588274
TI  - The genetics of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a disease characterised by diverse clinical
      manifestations and the presence of multiple autoantibodies. There are multiple
      aetiological factors involved in its pathogenesis. Genetic factors do play an
      important role and the major histocompatibility complex has been studied
      extensively and many human leukocyte antigen (HLA) associations have been
      reported. Twin and familial lupus studies confirm the importance of genetic
      factors in the development of SLE. Reported HLA associations range from that of
      HLA-DR3 in Caucasians to HLA-DR2 in Chinese, Japanese and American Blacks. These
      associations however may only represent linkage disequilibrium and not the actual
      susceptibility genes. Other non-major histocompatibility complex genes have also
      been reported to play important roles in the pathogenesis of lupus. The advent of
      molecular biological techniques has advanced the understanding of susceptibility
      genes in many diseases. The use of microsatellite genome scanning to study
      multiplex lupus families has yielded a wealth of information on clusters of
      susceptibility genes. The identification of these genes will be an important
      advance in the understanding of this complex disease.

PMID- 9588273
TI  - Systemic lupus erythematosus in Singapore.
AB  - The major initial clinical manifestations of systemic lupus erythematousus (SLE)
      were skin and mucous membrane involvement (52%), fever and malaise (48%),
      arthritis and arthralgias (44%). Lupus nephritis was diagnosed in 74% of patients
      and diffuse proliferative nephritis was the commonest histologic picture
      encountered. Except for a higher prevalence of anti-SS-A (Ro) (63%), other
      autoantibodies were within the normal range reported from Western countries.
      There was no significant association between HLA-A, B or DR specificities in 51
      Chinese patients, nor was there any differences seen in the polymorphism of
      tumour necrosis factor alpha gene (TNF-alpha). Arthritis was less commonly seen
      in males with SLE. Prevalences of leukopenia and antibodies to anti-SS-A (Ro) and
      anti-La (SS-B) antigens were lower in men. Late onset lupus patients (> 50 years
      of age) tended to have more insidious onset of disease, lower female predominance
      and less frequent complaints of fever, alopecia, arthritis and malar rash at
      presentation. The causes of death were often treatment related. Survival studies
      among 183 SLE patients during the period from 1970 to 1980 revealed a 5- and 10
      year survival rate of 70% and 60%, respectively. Infections and active lupus
      disease were 2 major causes of death. Research into SLE is targeted at increasing
      our understanding of the disease process and improving outcome and prognosis.

PMID- 9588275
TI  - Oral tolerance: mechanisms and therapy of autoimmune diseases.
AB  - Oral tolerance is a state of immune hyporesponsiveness induced by the oral or
      mucosal exposure to antigens. This state is dependent on the dose of the oral
      antigen administered, with a low dose stimulating regulatory T cell development
      leading to an active immune suppression that is transferable via T cells. The
      active mechanism appears to be a cytokine mediated immune deviation with a
      predominant Th2 and Th3 response (TGF-beta). In contrast, high dose oral antigens
      lead to clonal deletion and anergy. The active suppression of low dose oral
      tolerance can also suppress an unrelated immune response (bystander suppression)
      paving the way for therapy of autoimmune diseases like rheumatoid arthritis. Oral
      tolerance has been effective in the treatment of autoimmune diseases like
      experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA)
      and insulin-dependent diabetes in animals. However, recent studies in human
      autoimmune diseases have not been as effective but the results are encouraging
      and more work is required to understand the mechanisms involved and other factors
      that may modulate the response.

PMID- 9588276
TI  - The appropriate use of antineutrophil cytoplasmic antibody (ANCA) testing in
      rheumatic diseases.
AB  - The antineutrophil cytoplasmic antibody (ANCA) test is now available in most
      routine diagnostic immunology laboratories. Improvement, simplification and
      standardisation of the testing methodology have enabled it to become more
      reliable and accessible to clinicians. ANCA has strong association with and is
      most useful in the diagnosis and management of the ANCA-associated vasculitides
      which include Wegener's granulomatosis, microscopic polyarteritis, Churg-Strauss
      syndrome and primary pauci-immune necrotising and crescentic glomerulonephritis.
      It is found in lower frequency in the other vasculitides and collagen vascular
      diseases, in chronic inflammatory bowel disease and autoimmune liver disease, and
      in miscellaneous infective and neoplastic disorders. While the gold standard for
      ANCA testing remains the indirect immunofluorescence (IIF) assay, identification
      of ANCA-specific antigens such as proteinase 3 and myeloperoxidase has enabled
      the development of antigen-specific tests. The antigen-specific solid-phase
      assays have comparable sensitivity with IIF assays and improved specificity in
      some instances. However, appropriate use of the ANCA test requires full knowledge
      of its capabilities and limitations, and the results should always be correlated
      with clinical data. In particular, it is important to understand that it is not
      only test sensitivity and specificity, but patient selection that contributes to
      the positive predictive value and clinical relevance of the test result.

PMID- 9588277
TI  - Advances in antiphospholipid (Hughes') syndrome.
AB  - Fifteen years have passed since Hughes reported the detailed clinical description
      of antiphospholipid syndrome (APS), and it is now recognised as one of the most
      common prothrombotic disorders. Its main clinical features are recurrent
      thrombosis (both venous and arterial), recurrent pregnancy loss and
      thrombocytopenia associated with the presence of antiphospholipid antibodies
      (aPLs). aPLs are a heterogeneous group of autoantibodies detected by either
      clotting or immunological assays. They include lupus anticoagulant (LA),
      anticardiolipin antibodies (aCL) and antibodies against other phospholipids
      (PLs). Recently the aPLs family has expanded to include antibodies whose
      specificity are claimed to be directed not only towards PLs, but also towards
      plasma proteins and their complex with PLs. Animal models are providing important
      new data on clinical and pathogenic aspects of APS. The detection of antibodies
      against beta 2 glycoprotein I by a simple and rapid enzyme-linked immunosorbent
      assay (ELISA) may facilitate the recognition of "pathogenic" aCL in APS.
      Regarding the treatment of APS, long-term anticoagulation therapy is needed to
      prevent recurrences.

PMID- 9588278
TI  - Overview of imaging in rheumatologic diseases.
AB  - The role of radiology in rheumatologic diseases has for many years been confined
      to conventional radiography alone. The advances in medicine placed great demands
      on earlier and more accurate evaluation of these diseases. Conventional
      radiographs have been used as diagnostic aids and radiographic features and
      measurements are well established. However, the newer technologies, such as
      ultrasound, computed tomography and magnetic resonance imaging (MRI) have
      recently influenced accuracy of diagnosis and allowed for earlier detection and a
      more comprehensive evaluation of the results of therapy. One leading example is
      the significant role MRI plays in the early detection of avascular necrosis,
      especially of the hips. The clinical benefits of the newer modalities in
      radiology are being increasingly recognised and its full potential realised by
      both rheumatologists and radiologists.

PMID- 9588280
TI  - Rheumatoid arthritis--a review.
AB  - Rheumatoid arthritis, a common chronic inflammatory arthritis, tends to run a
      more benign course in patients from the community than those seen at hospitals.
      The aetiology is unknown but the disease is postulated to result from the
      interaction between genetic and environmental factors. The strongest genetic
      association is with the major histocompatibility complex (MHC) Class II antigen
      HLA DR 4, although not more than 50% of the genetic susceptibility is due to MHC
      genes. In early disease the pathogenesis is thought to be T cell mediated whereas
      in late disease the mechanisms are T cell independent, with destruction
      contributed to by autonomous fibroblast like synoviocytes. The diagnosis is made
      on clinical groups. Management is directed at controlling active synovitis so
      that joint damage is limited. The early use of a slow acting anti-rheumatic drug
      is now advocated, as studies have shown that they can potentially prevent or
      limit the progression of disease. Biological therapies are still experimental but
      may hold promise for the future.

PMID- 9588279
TI  - Imaging of thoracic manifestations of scleroderma.
AB  - Radiographs illustrating the various thoracic manifestations of systemic
      sclerosis are shown. These include pulmonary parenchymal disease e.g.
      interstitial pneumonitis and pneumonia, pleural disease (pneumothorax), cardiac
      involvement, oesophageal disease, bony changes and soft tissue calcification. The
      use of chest radiography and other imaging modalities such as high resolution
      computerised tomography (HRCT) of the thorax is discussed.

PMID- 9588281
TI  - Lipid disorders and rheumatic diseases.
AB  - Lipid abnormalities can exist in patients with rheumatic diseases. Many
      mechanisms give rise to these abnormalities and include treatment with
      corticosteroids and upregulation of certain cytokines in active rheumatic
      disease. Premature atherosclerosis can occur in these patients with significant
      morbidity and mortality. Greater awareness and earlier treatment of these lipid
      problems may lead to better outcomes.

PMID- 9588282
TI  - Managing problem gout.
AB  - For the management of acute gouty arthritis, non-steroidal anti-inflammatory
      drugs (NSAIDs) are the drugs of choice. In recent years, the use of colchicine
      has declined because of its frequent adverse reactions, and its reduced efficacy
      when administered more than 24 hours after onset of an acute attack. Intra
      articular corticosteroid therapy (e.g. methylprednisolone acetate) is indicated
      for the treatment of acute mono or oligoarticular gouty arthritis in aged
      patients, and in those with co-morbid conditions contraindicating therapy with
      either NSAIDs or colchicine. Oral corticosteroids (e.g. prednisone), and both
      parenteral corticotrophin (ACTH) and corticosteroids (e.g. intramuscular
      triamcinolone acetonide) are valuable, relatively safe alternate treatment
      modalities in those with polyarticular attacks. For the treatment of
      hyperuricaemia and chronic gouty arthritis, allopurinol is the preferred urate
      lowering drug. Its toxicity in elderly individuals, those with renal impairment,
      and in cyclosporine-treated transplant patients can be minimised by adjusting the
      initial dose according to the patient's creatinine clearance. In those
      experiencing cutaneous reactions to allopurinol, cautious desensitisation to the
      drug can be achieved using a schedule of gradually increasing doses. The
      therapeutic usefulness of uricosuric drugs is limited by the presence of renal
      impairment, occurrence of intolerable side-effects, or concomitant intake of
      salicylates. They are particularly indicated in patients allergic to allopurinol
      and in those with massive tophi requiring combined therapy with both allopurinol
      and a uricosuric.

PMID- 9588283
TI  - Osteoporosis--the need for a paradigm shift.
AB  - Osteoporosis is a potentially devastating illness and causes morbidity and
      mortality from fragility fractures at the wrist, spine and hip. Currently, the
      illness can be detected before the fractures occur using dual energy X-ray
      absorptiometry and many preventive and therapeutic options exist. Efforts should
      be directed at helping the population at large achieve a healthy peak bone mass
      and adopt lifestyle habits which benefit bone mass. For those at high risk of
      fractures or who have already suffered an osteoporotic fracture, many
      pharmacological agents have been shown to reduce the risk of subsequent
      fractures. Hormone replacement therapy and bisphosphonates have the best efficacy
      data at present but there are likely to be more options in the near future.
      Hence, there is a need for a paradigm shift in that osteoporosis should not be
      thought of as an illness that starts at the point of fracture. Instead, it should
      be actively assessed and treated before fractures occur.

PMID- 9588284
TI  - Intra-synovial corticosteroid injections in juvenile chronic arthritis--a review.
AB  - Locally injected intra-synovial corticosteroids are an important and effective
      part of treatment for juvenile chronic arthritis (JCA). They work rapidly,
      effectively and safely. They are most useful for limited joint, tendon sheath or
      bursal involvement in pauciarticular JCA or the few most active joints in
      polyarticular or systemic JCA while awaiting the onset of action of disease
      modifying anti-rheumatic drugs. This article includes a brief history of intra
      synovial steroid use, the mechanisms of action in decreasing inflammation and
      contraindications, as well as local and systemic complications. Important
      contraindications include infection, prostheses, arthroscopy, surgical
      procedures, damaged joints and hypersensitivity. The commonest complication is
      subcutaneous atrophy while serious complications include infection and damage to
      the joint and surrounding structures. Proper technique, use of imaging and
      adequate analgesia or anaesthesia, post injection rest and subsequent
      mobilisation are important. The efficacy and duration of action of the various
      steroids available are discussed. Long-acting microcrystalline steroids such as
      triamcinolone hexacetonide are useful for prolonged remission. Repeated
      injections can be safe and effective. Failure may be due to incorrect technique,
      insufficient or short-acting steroid, poor general disease control or intra
      synovial septa.

PMID- 9588285
TI  - Musculoskeletal pain clinic in Singapore--sacroiliac joint somatic dysfunction as
      cause of buttock pain.
AB  - Buttock pain was a predominant symptom in a series of patients seen with
      recalcitrant "backache" in the author's pain clinic which has a musculoskeletal
      emphasis. Assessment suggested the sacroiliac joint as the culprit pain generator
      and patients underwent confirmatory testing which included fluoroscopy-guided
      intra-articular injections of lignocaine and steroid along with combined
      therapeutic modalities of oral analgesics, physical therapy, manual medicine
      techniques and ergonomic assessments. Two case reports illustrate this condition
      which is probably under-recognised and inadequately addressed locally.

PMID- 9588287
TI  - The role of occupational therapy in rheumatoid arthritis management.
AB  - Occupational therapy has been defined as the science of eliciting adaptive
      responses characterised by prescription of purposeful activities that are goal
      orientated to maximise independence and functional life skills in disability
      management. The scope of its intervention in the rehabilitation of rheumatoid
      arthritis is outlined with an overview of literature update on patient education.

PMID- 9588286
TI  - A case of sulindac-induced enteropathy resulting in jejunal perforation.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for
      rheumatic conditions. Their effects on the upper gastrointestinal tract are well
      recognised. Clinically important damage to the small intestines is less common
      and often unrecognised. We report a case of sulindac-induced jejunal perforation
      in a rheumatoid arthritis (RA) patient with previous gastrectomy for gastric
      carcinoma. The prevalence, diagnosis, pathogenesis and treatment options of NSAID
      induced enteropathy will be discussed.

PMID- 9588288
TI  - Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: a brief
      review of a rare condition.
AB  - Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is an
      osteoarticular-skin syndrome characterised by sterile inflammatory arthro
      osteitis of the anterior chest wall. It is associated with various skin
      conditions including palmoplantar pustulosis, severe acnes and pustular
      psoriasis. A link between SAPHO syndrome and seronegative spondyloarthropathies
      has been suggested over the last 10 years. SAPHO syndrome mainly affects young
      and middle-aged adults. Treatment of SAPHO syndrome remains empirical as the
      underlying aetiopathogenesis is unclear.

PMID- 9588289
TI  - Medicine and surgery--history, change and challenge.
AB  - In this lecture I will discuss the history of medicine and surgery in ancient
      China and India, and examine the value systems underpinning medical and surgical
      practice in these two civilizations. I will touch on some of the enduring "Asian"
      values that may be abstracted from the past to ensure that modern medicine along
      with surgery remains first and foremost a moral activity that renders public
      service, and is practiced with compassion and altruism. I will outline briefly
      the spread of Western or allopathic medicine into Asia and the rest of the world.
      Finally, I will look at the challenges that confront us today with the intrusion
      of high technology and the market economy into the practice of our profession. I
      will show how this has fundamentally altered the way we practise medicine and
      surgery and the delivery of health care.

PMID- 9588290
TI  - Tan Tock Seng Hospital: some recollections from 1942 to 1997.

PMID- 9588291
TI  - The rich legacy of Tan Tock Seng Hospital includes that of being a medical
      college in 1943 to 1944.

PMID- 9588292
TI  - A letter from Jerusalem: some questions on the future of the scientific journal.

PMID- 9588294
TI  - One hundred years of Emile Durkheim's Suicide: A Study in Sociology.

PMID- 9588293
TI  - Psychiatry and paedophilia: a major public health issue.
AB  - OBJECTIVE: The aim of this study was to provide a brief review of current
      perspectives on paedophilia as well as some suggestions regarding the place of
      psychiatry in dealing with the problem. METHOD: A literature survey was
      conducted. RESULTS: Child sexual abuse has unfortunately been ignored and
      minimised by psychiatry until recently. The current evidence strongly indicates
      that it is a common event which is highly likely to cause both short- and long
      term harm to its victims. The perpetrators generally are psychiatrically
      otherwise 'normal' men who are skilled at both planning their offending
      behaviours and denying their existence. CONCLUSIONS: Psychiatrists have an
      important role to play in assessment and treatment of both offenders and victims,
      although they may have to learn new clinical skills. Their preventative role is
      also important, particularly in the field of public education.

PMID- 9588295
TI  - The relationship between admission to hospital with chest pain and psychiatric
      disorder.
AB  - OBJECTIVE: Psychosocial variables have been identified as important predictors of
      outcome in patients with chest pain. Most attention has focused on patients with
      ischaemic heart diseases or those in outpatient settings. This paper compares
      focuses on inpatients, and compares patients with ischaemic heart disease to
      those with non-specific chest pain. METHOD: A search of the literature on chest
      pain and psychiatric disorder from 1972 onwards using Medicine, Index Medicus and
      the bibliographies of retrieved articles. RESULTS: One-third of patients admitted
      with acute chest pain have psychiatric disorder as measured by standardised
      interviews. Patients who have had psychiatric symptoms prior to admission and
      those with non-specific pain appear to be most at risk of continuing psychiatric
      morbidity. In patients with ischaemic heart disease, psychiatric symptoms on
      admission are more strongly related to subsequent social outcome than variables
      such as severity of infarct or the presence of angina. Psychiatric symptoms may
      also effect physical morbidity and possibly mortality, although further research
      is required to clarify the latter finding. In patients with nonspecific pain,
      further research is indicated to identify aetiological and maintaining factors
      for continued non-specific pain. There is, however, a strong association with
      alcohol and cigarette use. CONCLUSIONS: The prediction of outcome requires
      careful assessment of previous or current psychiatric symptoms in patients
      admitted with chest pain, irrespective of underlying diagnosis. Early
      intervention with psychological treatment for patients with non-specific chest
      pain is indicated; this may also involve help to reduce smoking. There is also
      further evidence that mortality following myocardial infarction is closely linked
      to psychiatric disorder, although prior psychiatric disorder may be more
      important than 'post-infarction' depression. Larger and more methodologically
      rigorous studies are required to further clarify these findings.

PMID- 9588296
TI  - The relationship between fatigue, psychological and immunological variables in
      acute infectious illness.
AB  - OBJECTIVE: The aim of this paper is to explore the longitudinal relationships
      between physical and psychological symptoms and immunological factors following
      acute infective illnesses. METHOD: Preliminary data from a prospective
      investigation of patients with serologically proven acute infectious illnesses
      due to Epstein-Barr virus (EBV), Ross River virus (RRV) or Q fever are reported.
      Patients were assessed within 4 weeks of onset of symptoms and then reviewed 2
      and 4 weeks later. Physical illness data were collected at interview.
      Psychological and somatic symptom profiles were assessed by standardised self
      report questionnaires. Cell-mediated immune (CMI) function was assessed by
      measurement of delayed-type hypersensitivity (DTH) skin responses. RESULTS:
      Thirty patients who had been assessed and followed over the 4-week period
      (including 17 patients with EBV, five with RRV and eight with Q fever) were
      included in this analysis. During the acute phase, profound fatigue and malaise
      were the most common symptoms. Classical depressive and anxiety symptoms were not
      prominent. Initially, 46% of cases had no DTH skin response (i.e. cutaneous
      anergy) indicative of impaired cellular immunity. Over the 4-week period, there
      was a marked improvement in both somatic and psychological symptoms, although
      fatigue remained a prominent feature in 63% of subjects. The reduction in
      reported fatigue was correlated with improvement in the DTH skin response (p =
      0.001) and with improvement in General Health Questionnaire (GHQ) scores (p <
      0.01). CONCLUSIONS: Acute infectious illnesses are accompanied by a range of
      nonspecific somatic and psychological symptoms, particularly fatigue and malaise
      rather than anxiety and depression. Although improvement in several symptoms
      occurs rapidly, fatigue commonly remains a prominent complaint at 4 weeks.
      Resolution of fatigue is associated with improvement in cell-mediated immunity.

PMID- 9588297
TI  - The relationship between psychiatric illness and the circadian pattern of heart
      rate.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      psychiatric status and the circadian pattern of heart rate. METHOD: Serial 24
      hour recordings of minute average heart rate were obtained from 30 normal
      volunteers and 200 patients representing a range of DSM-III-R diagnoses. Records
      were compared in terms of their circadian 'morphology' and grouped into different
      pattern types. The distribution of patterns in different diagnoses was analysed
      statistically. RESULTS: It was found that states such as generalised anxiety and
      depression are strongly associated with a distinctive circadian pattern, whereas
      others such as somatoform disorder show more variation in this regard. Serial
      recordings show that the relationship between psychiatric status and circadian
      pattern is state-dependent; a change in clinical status leads to a change in the
      circadian pattern. CONCLUSIONS: The presented findings together suggest that
      there is a systematic relationship between psychiatric status and heart rate in
      which core physiological differences between certain states are reflected in
      distinctively different circadian patterns of activity. The state-dependent
      nature of this relationship suggests obvious practical applications, and examples
      are given of how these adjunct data can provide objective indices of clinical
      status and change. At a theoretical level, the physiological dimension revealed
      by these data may help to define more reliable syndromal distinctions between
      various clinical manifestations and hence contribute to a more robust nosology.

PMID- 9588298
TI  - The Health of the Nation Outcome Scales in psychiatric hospitalisation: a
      multicentre study examining outcome and prediction of length of stay.
AB  - OBJECTIVE: The Health of the Nation Outcome Scales (HoNOS) is a reliable
      instrument, useful in detecting change in symptoms and functioning during
      psychiatric hospitalisation. The present study examines its utility in predicting
      length of stay of patients in six private psychiatric hospitals in four
      Australian States. METHOD: The HoNOS was administered on admission and discharge
      in six private psychiatric hospitals in Australia. RESULTS: There were
      significant differences in total score and in all sub-scales between admission
      and discharge. There were no significant associations between total HoNOS scores
      and length of stay, either for individual hospitals or for specific diagnosis
      related groups. There were only very weak associations, of doubtful practical
      clinical significance, between length of stay of all patients and individual
      HoNOS sub-scales. CONCLUSION: While the HoNOS is of some value in providing a
      readily administered and understood measure for clinicians, on the basis of these
      findings it is unlikely to be of utility in predicting length of stay or in
      offering a 'gate-keeping' service in decision-making in regard to the allocation
      of resources for individual patients.

PMID- 9588299
TI  - Staff response to abuse histories of psychiatric inpatients.
AB  - OBJECTIVE: In the context of numerous studies demonstrating that a significant
      proportion of psychiatric inpatients have been sexually or physically abused at
      some point in their lives this study ascertained the responses of staff in a
      psychiatric inpatient unit to knowledge that patients had been subjected to
      sexual or physical abuse, in childhood or adulthood. METHOD: The medical records
      of 100 consecutive admissions were examined. Staff response was measured in terms
      of: (i) acquiring information about previous treatment for, or disclosure of,
      abuse; (ii) providing information, support or counselling during hospitalisation;
      (iii) reporting to legal authorities; and (iv) referring for ongoing abuse
      counselling. RESULTS: Of the 32 patients who were documented as having disclosed
      abuse 11 files included documentation of previous treatment or disclosure; none
      were reported to have received support, counselling or information while in
      hospital; and three referrals were made for ongoing counselling. None of the 52
      separate instances of abuse were reported to the authorities. Demographic,
      diagnostic, clinical and treatment variables, as well as the four abuse
      categories, were analysed for possible linkage to probability of staff response
      in each of the four response categories. CONCLUSIONS: It was hypothesised that
      the low staff response rate is not unique to the particular unit evaluated here.
      Recommendations are offered regarding the need for unit policies ensuring routine
      abuse inquiry and for staff training about how to respond to abuse disclosures.

PMID- 9588300
TI  - Learning organisations: a suitable model for improving mental health services?
AB  - OBJECTIVE: The aim of this paper was to describe an organisational model that has
      created interest in recent business management literature as supporting learning,
      adaptation and continuous improvement. METHOD: Some key features of the
      literature on learning organisations are outlined, including the values and
      processes involved, together with a structural and cultural template that has
      been applied to a community child and adolescent mental health service. Some
      blocks to learning and the leadership skills required to develop adaptive
      services are described. RESULTS: The experience of applying the model has led to
      a change in mental health service organisational structure and culture towards
      greater support for research, quality improvement, experimentation and
      adaptation. CONCLUSIONS: The learning organisation model offers a more
      comprehensive framework for designing adaptive mental health services and
      supporting quality management practices than any other recent organisational
      form.

PMID- 9588301
TI  - The community treatment order: clinical and ethical issues.
AB  - OBJECTIVE: In the light of recent legislation, this paper reviews the
      implementation of the Community Treatment Order (CTO) in terms of clinical
      efficacy and ethical issues involved in its use. The debate surrounding the
      introduction of CTOs in other countries is explored. METHOD: A Medline search was
      conducted and references of recent articles followed up, with attention to
      Australian, New Zealand and international trends. A review of relevant
      legislation and government reports was conducted. RESULTS: There has been limited
      debate in the Australian and New Zealand literature concerning the operation of
      CTOs. Despite their increasing and widespread use, there is a paucity of research
      on the efficacy of CTOs. Concerns about their negative effects on civil liberties
      have been stressed in the United Kingdom and American literature. CONCLUSIONS: If
      the continued use of CTO is to be justified, both clinically and from the civil
      liberties perspective, controlled research needs to be carried out to identify
      whether CTOs are more effective than comprehensive assertive community outreach
      programs in reducing relapse rates and hospitalisation, and increasing
      compliance. Clinical guidelines concerning who is most likely to respond to such
      orders need to be developed. Alternatives to the CTO are explored, and future
      directions in research are outlined.

PMID- 9588302
TI  - The implications of legislative change on the future of psychiatric nursing in
      Victoria.
AB  - OBJECTIVE: The aim of this paper is to explore the potential implications of the
      Nurses Act introduced in 1993 upon psychiatric nursing in Victoria. Essentially
      this Act abolished the existing separate undergraduate education for psychiatric
      nursing. The focus of this paper is to explore the potential implications of this
      legislative change to the psychiatric nursing profession, particularly in light
      of relevant research findings. METHOD: In order to ascertain the impact of
      legislative change, a survey of psychiatric nursing content was conducted in
      Schools of Nursing throughout Victoria. RESULTS: A 100% response rate was
      achieved. The responses indicated that little alteration had been made to
      existing-general nursing courses to incorporate the change in legislation. The
      compulsory psychiatric nursing content varies from nil to 17.4% of the total
      curriculum. CONCLUSIONS: The theory and practice of psychiatric nursing
      constitute only a small proportion of undergraduate curricula. In view of the
      comparative unpopularity of psychiatric nursing as a career option for
      undergraduate students, the implications of this situation for the future
      psychiatric nursing workforce are serious.

PMID- 9588303
TI  - A longitudinal study comparing bereavement phenomena in recently bereaved
      spouses, adult children and parents.
AB  - OBJECTIVE: The study investigated previous research findings and clinical
      impressions which indicated that the intensity of grief for parents who had lost
      a child was likely to be higher than that for widows/widowers, who in turn were
      likely to have more intense reactions than adult children losing a parent.
      METHOD: In order to compare the intensities of the bereavement reactions among
      representative community samples of bereaved spouses (n = 44), adult children (n
      = 40) and parents (n = 36), and to follow the course of such phenomena, a
      detailed Bereavement Questionnaire was administered at four time points over a 13
      month period following the loss. RESULTS: Measures based on items central to the
      construct of bereavement showed significant time and group differences in
      accordance with the proposed hypothesis. More global items associated with the
      construct of resolution showed a significant time effect, but without significant
      group differences. CONCLUSIONS: Evidence from this study supports the hypothesis
      that in non-clinical, community-based populations the frequency with which core
      bereavement phenomena are experienced is in the order: bereaved parents >
      bereaved spouses > bereaved adult children.

PMID- 9588304
TI  - Coroners' records of rural and non-rural cases of youth suicide in New South
      Wales.
AB  - OBJECTIVE: The aim of this study is to compare the frequency of certain putative
      risk factors for youth suicide in New South Wales (especially use of alcohol,
      social class, unemployment, and internal migration) in metropolitan and rural
      settings. METHOD: A review of 137 files for 10-19-year-old subjects judged by the
      Coroner to have committed suicide in 1988-1990 was carried out. RESULTS: One
      hundred and fifteen males and 21 females were identified (one subjects sex was
      unavailable). The male-female ratio was higher in rural (13.0) areas than non
      rural (4.9 chi 2 = 12.14, p < 0.01). Of 27 subjects migrating within Australia,
      most migrated in a rural direction, and most to rural shires. Unemployment was
      somewhat more common among rural (38.5%) than non-rural (28.9%) subjects (chi 2 =
      0.75, p = 0.39). Eleven of 50 non-rural parents of the deceased, but none of the
      11 rural parents, were ranked as being in social classes 2 or 3. Alcohol
      consumption appeared more common in rural shires (44%) than metropolitan areas
      (32.9%), but this was not statistically significant. Medical services were less
      utilised prior to death in rural (15%) than non-rural (25%) areas (chi 2 = 1.69,
      p = 0.19), and a psychiatric diagnosis was recorded more commonly in non-rural
      areas. CONCLUSIONS: Incomplete coronial file data and relatively small numbers
      limit this study's conclusions. Male suicides, principally by firearms,
      predominated in rural areas. Youth firearm access remains highly relevant to
      rural communities. Possible trends among rural subjects toward rural migration,
      higher unemployment, lower social class and lower medical attendance may point to
      resource deprivation among this group; these matters require further
      investigation.

PMID- 9588305
TI  - Paedophilia: a review of the evidence.
AB  - OBJECTIVE: The aim of this study was to critically review the literature
      concerning the nature ane prevalence of paedophilia. METHOD: The literature of
      the past 30 years was examined in relation to the author's clinical experience
      and with emphasis on methodologically appropriate empirical studies. RESULTS:
      Concern and reporting of child-adult sexual activity has increased markedly in
      the last decade, although its prevalence has not increased at least since the
      1960s. The prevalence in women can be as high as 60%, depending on the definition
      and method of enquiry used, and female compared to male victims report more
      negative effects, although a percentage of both men and women report the
      experience as positive. Validation of effects requires multivariate statistical
      analysis. Current pro-active procedures to identify paedophiles detect those who
      victimise boys but do not detect the much greater number of paedophiles who
      victimise girls. Perpetrators are known to the majority of their female and male
      victims, and those reported are almost all male; most boys do not consider their
      prepubertal experiences with older women abusive. Relapse prevention, the current
      most popular treatment, has been shown to be ineffective for incarcerated child
      molesters. CONCLUSIONS: Child-adult sexual activity should be opposed as an
      infringement of children's rights rather than requiring a false belief that it is
      invariably harmful; whether it should be mandatory for therapists to report it
      requires examination. Scientifically appropriate evaluation should be an
      essential component of current treatment programs.

PMID- 9588306
TI  - A pilot study of computer-aided vicarious exposure for obsessive-compulsive
      disorder.
AB  - OBJECTIVE: This study reports the use of an interactive computer program to
      instruct vicarious exposure and ritual prevention for obsessive-compulsive
      disorder (OCD). METHOD: Thirteen OCD volunteers and 10 non-OCD volunteers
      completed three 45-minute sessions at weekly intervals. Subjects with OCD
      completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Padua Inventory
      (PI) and the Beck Depression Inventory (BDI) 1 week prior to and 1 week after the
      three computer treatment sessions. Non-OCD subjects only completed these measures
      at baseline, allowing confirmation that they had no significant level of OCD
      symptomatology. RESULTS: In the OCD subjects, scores fell significantly on the PI
      and BDI, and Y-BOCS scores fell non-significantly. Engagement in vicarious
      exposure with ritual prevention improved from sessions 1-3. Compared to the non
      OCD participants, OCD subjects did less vicarious exposure in session 1 but not
      sessions 2 and 3. Performance of vicarious exposure by OCD subjects in session 1
      correlated with pre-post improvement in PI and BDI scores. CONCLUSIONS: The
      vicarious exposure program may have a role to play as an adjunct in behaviour
      therapy.

PMID- 9588307
TI  - Comorbidity of bipolar and personality disorder.
AB  - OBJECTIVE: The aims of this study were to determine the prevalence of personality
      disorder in a sample of patients with well-documented bipolar disorder, and to
      assess the effects of comorbidity. METHOD: The sample (n = 42) was drawn from
      patients currently case-managed within a community treatment program who fully
      met DSM-IV criteria for bipolar I disorder. The International Personality
      Disorder Examination, a structured interview, was used to diagnose personality
      disorder. The Brief Symptom Inventory assessed overall levels of psychological
      symptoms. RESULTS: Seven of the 13 men (55%) in the sample had 10 personality
      disorder diagnoses and 12 of the 29 women (41%) had 28 diagnoses, an overall
      prevalence of 45%. Hospital admission rates and all measures of psychological
      symptoms and impairment were significantly elevated in the comorbid group, who
      found medication significantly less helpful. CONCLUSIONS: Comorbid personality
      disorder was common in the sample studied, which was representative of Australian
      patients treated in public community psychiatry programs. However, only three
      (7%) had a personality disorder diagnosis recorded in their case notes,
      reflecting clinicians' reluctance to apply what is widely viewed as a pejorative
      and therapeutically nihilistic label. New treatments for personality disorder
      have proven effective within both public and private psychiatric settings, so
      that underdiagnosis represents undertreatment. The findings suggest that
      clinicians should be more vigilant for comorbid personality and bipolar disorder,
      and less reluctant to diagnose it.

PMID- 9588308
TI  - Predictability of rehospitalisation over 5 years for schizophrenia, bipolar
      disorder and depression.
AB  - OBJECTIVE: The aim of this study was to examine the rate of rehospitalisation for
      schizophrenia, bipolar disorder and depression over a 5-year period in Tasmania,
      and to identify predictors of the number and duration of readmissions. METHOD:
      The Tasmanian Mental Health Register was used to study the 5-year pattern of
      rehospitalisation for all patients admitted to a Tasmanian public psychiatric
      inpatient facility with a primary diagnosis of schizophrenia, bipolar disorder or
      depression, in 1983 or 1984. RESULTS: Seventy-one percent of patients receiving a
      diagnosis of schizophrenia were readmitted in the 5-year period, compared to 59%
      for bipolar disorder and 48% for depression. For all three diagnoses, the number
      of prior admissions was a predictor of the number of readmissions and the total
      number of days spent in hospital in the follow-up period. Age and sex also had
      significant effects, which varied across diagnostic groups. CONCLUSIONS: A
      substantial proportion of patients hospitalised for schizophrenia, bipolar
      disorder or schizophrenia were rehospitalised during the next 5 years. Patients
      with more previous admissions had more readmissions than those with fewer
      previous admissions.

PMID- 9588309
TI  - Puerperal psychosis: associated clinical features in a psychiatric hospital
      mother-baby unit.
AB  - OBJECTIVE: Current psychiatric diagnostic systems do not regard puerperal
      psychosis as a separate entity. However, there is continuing debate about the
      validity and clinical utility of this concept. This paper aims to investigate the
      prognostic importance of a number of clinical features in a sample of patients
      with puerperal psychosis. METHOD: A retrospective case note study was conducted
      on 42 consecutive admissions to a mother-baby unit in a psychiatric hospital.
      Data were collected on a range of variables, and diagnoses made according to DSM
      III-R and RDC criteria for puerperal psychosis. RESULTS: Maternal hostility
      toward the baby was the only studied variable to increase the likelihood of the
      baby being cared for by someone other than the mother, indicating the mother's
      inability to safely care for the baby. CONCLUSIONS: These findings tentatively
      suggest that it is maternal hostility toward the baby, not puerperal psychosis
      per se that is associated with foster care.

PMID- 9588310
TI  - Withdrawal reactions associated with venlafaxine.
AB  - OBJECTIVE: The aim of this paper is to describe discontinuation syndromes
      associated with abrupt and tapered withdrawal fo venlafaxine, and to document
      that withdrawal symptoms may occur after missing a single dose. CLINICAL PICTURE:
      We report on two patients prescribed venlafaxine. One developed a broad range of
      serious side effects after reaching a dose of 300 mg a day, and a severe
      withdrawal syndrome (including hallucinations) during a slow taper regime. The
      second had severe discontinuation symptoms during and aborting a slow taper
      regime, and described withdrawal responses after missing a single dose of
      venlafaxine. CONCLUSIONS: As for the short-acting selective serotonin re-uptake
      inhibitors, severe discontinuation reactions may occur with venlafaxine,
      seemingly marked most distinctly by headache, nausea, fatigue, dizziness and
      dysphoria, and may make cessation of the drug extremely difficult. Two strategies
      for addressing the concern are considered.

PMID- 9588311
TI  - Hyponatraemia associated with the use of selective serotonin re-uptake
      inhibitors.
AB  - OBJECTIVE: The aim of this study is to examine the frequency and severity of
      hyponatraemia in a psychogeriatric inpatient population taking selective
      serotonin re-uptake inhibitors (SSRIs). METHOD: Casenotes for 1 year were
      reviewed and 53 patients with 55 admissions were identified. Eighteen were
      treated with fluoxetine and 37 with paroxetine. Five (28%) of the patients on
      fluoxetine and eight (22%) on paroxetine were, or became, hyponatraemic. RESULTS:
      The SSRI was discontinued in two symptomatic patients. Serum sodium returned to
      normal in nine patients maintained on the SSRI. Two patients maintained on an
      SSRI remained hyponatraemic but asymptomatic. CONCLUSIONS: Hyponatraemia may be a
      relatively common early asymptomatic side effect of SSRIs, especially in older
      women. Serum sodium should be measured before commencing an SSRI and monitored
      during the first month. Any patient who exhibits symptoms of hyponatraemia, or
      whose depression apparently worsens, while on an SSRI must have their serum
      sodium measured. Discontinuation of the SSRI may be avoidable if serum sodium
      levels can be closely monitored.

PMID- 9588312
TI  - Obsessional symptoms associated with risperidone treatment.
AB  - OBJECTIVE: The aim of this paper is to report the occurrence of obsessional
      symptoms with risperidone treatment in a patient with no past history of
      obsessive-compulsive symptoms. CLINICAL PICTURE: A 26-year-old, single, Chinese
      lady with a chronic untreated schizophrenic illness was prescribed risperidone
      after she experienced side effects with other antipsychotic medication. After the
      second week on risperidone, she developed obsessional symptoms. TREATMENT AND
      OUTCOME: The obsessional symptoms responded to treatment with low dose
      clomipramine. CONCLUSION: The potential for the newer antipsychotic medication to
      precipitate or exacerbate obsessive-compulsive symptoms during treatment for
      schizophrenia must be borne in mind.

PMID- 9588313
TI  - Grammatical pedantry?

PMID- 9588314
TI  - Who should do cross-cultural research?

PMID- 9588315
TI  - Therapeutic community reborn?

PMID- 9588316
TI  - Patient-therapist sex: a search for sex or sensitivity?

PMID- 9588317
TI  - On Viktor Frankl's legacy.

PMID- 9588318
TI  - Integration or 'integration'?

PMID- 9588319
TI  - Shared care but not consultation-liaison psychiatry.

PMID- 9588320
TI  - 'Biological signals' to 'biological signals and receptors'

PMID- 9588321
TI  - Hypothalamic relationships between interleukin-6 and LHRH release affected by
      bacterial endotoxin in adult male rats. Involvement of the inhibitory amino acid
      system
AB  - Immune system alterations coexist with modifications in the reproductive axis.
      The bacterial endotoxin lipopolysaccharide (LPS) has inflammatory effects and
      stimulates cytokine release in the hypothalamus where LHRH neurons are located.
      LPS inhibition of LHRH release at hypothalamic level appears to be associated
      with modifications in the cerebral immune system. Central and peripheral LPS
      administration induces the expression and release of several cytokines in the
      central nervous system. Hence the present study was designed to investigate a
      possible function of the interleukin-6 (IL-6) stimulated by LPS in the regulation
      of LHRH secretion. Male rats were decapitated, and the preoptic mediobasal
      hypothalamic area (PO/MBH) was dissected and superfused with Earle's balanced
      salt solution. Superfusate fractions were collected at 15-min intervals after a
      60-min stabilization superfusion period. LPS (100 ng/ml) and IL-6 receptor
      antagonist (IL-6ra) were then added to the superfusion medium over 1 h in two
      different experimental designs: (1) LPS only and (2) LPS followed by IL-6ra,
      performed in different experiments. This was followed by a washout period. The
      PO/MBH fragments were then subjected to a 56 mM K+ stimulus. Control PO/MBH
      fragments were continuously superfused with Earle's solution. As expected, LHRH
      release was significantly reduced (p < 0.05) during and following exposure to
      LPS. At the same time, IL-6 concentrations significantly increased in the
      superfusion medium compared with the control group. IL-6ra significantly (p <
      0.01) potentiated the inhibitory effect of LPS on LHRH secretion. On the bases of
      previous papers indicating a stimulatory effect of IL-6 on LHRH release it could
      be considered that the potentiation of IL-6ra of the inhibitory effect of LPS on
      LHRH could be the consequence of the lack of the stimulatory effect of IL-6 on
      LHRH produced by the receptor antagonist. IL-6ra also increased IL-6 levels
      measured in medium probably due to a decrease in the metabolization induced by
      the blockage of the receptors and the consequent accumulation of IL-6 in the
      media. These results could indicate that IL-6 partly attenuates the inhibitory
      effect of LPS on LHRH release. These observations indicate that there is an
      increase in IL-6 release that becomes significant at the same time when LHRH
      release is decreased. Also, depolarizing concentrations of K+ (56 mM) did not
      increase IL-6 release, while LHRH release from the hypothalamic fragments was
      significantly increased. These data suggest that the inhibitory effect of LPS on
      LHRH release may be explained by the stimulation of other cytokines than IL-6,
      meanwhile the augmented levels of IL-6 probably released via a nonneuronal source
      was shown to be higher when LHRH was decreased. This could confirm the
      stimulatory role of IL-6 on LHRH release.

PMID- 9588322
TI  - Circadian rhythms in adenohypophysial hormone levels and hypothalamic monoamine
      turnover in mycobacterial-adjuvant-injected rats
AB  - The effect of Freund's adjuvant injection on 24-hour variation in circulating
      ACTH, prolactin, growth hormone (GH) and thyroid-stimulating hormone (TSH)
      levels, and of hypothalamic norepinephrine (NE) content and dopamine (DA) and
      serotonin (5HT) turnover was examined in adult rats. In control rats, serum ACTH
      and prolactin exhibited peak values at the light-dark transition while the
      maximum in TSH was found in the late afternoon. GH levels did not vary on a 24
      hour basis. In Freund's-adjuvant-injected rats, 24-hour variations in TSH levels
      became blunted while 24-hour variations in prolactin and ACTH persisted. Freund's
      adjuvant treatment augmented serum ACTH and prolactin levels, and decreased GH
      and TSH levels. Hypothalamic NE content, and turnover of DA and 5HT varied on a
      24-hour basis in rats receiving adjuvant's vehicle. The NE content of the
      anterior, medial and posterior hypothalamus peaked at 04.00 h, while that of the
      median eminence attained its maximum at 16.00-20.00 h. Maxima in hypothalamic DA
      and 5HT turnover ocurred at 04.00 h regardless of the region examined. In
      Freund's-adjuvant-injected rats, reduced amplitude of daily variations of NE
      content in the median eminence and anterior and medial hypothalamus, as well as a
      phase advance in the 24-hour rhythm of the posterior hypothalamic NE content were
      seen. Mycobacterial adjuvant injection also reduced the amplitude of circadian
      rhythm in hypothalamic 5HT turnover, shifted the maximum in median eminence DA
      turnover towards light-dark transition, and decreased the amplitude of DA
      turnover rhythm in the anterior, medial and posterior hypothalamus.
      Administration of the immunosuppressant drug cyclosporine restored the augmented
      ACTH and prolactin levels and the depressed GH and TSH levels found in Freund's
      adjuvant-injected rats. Cyclosporine was also effective to restore 24-hour
      rhythmicity of serum ACTH and TSH, but not of prolactin levels. Immunosuppression
      restored rhythmicity of NE content and of DA and 5HT turnover in anterior, medial
      and posterior hypothalamic regions. Cyclosporine did not modify the effect of
      Freund's adjuvant on median eminence but in was able to counteract the changes in
      the DA and 5HT turnover in the median eminence found after immunization. The
      results are in accord with a significant effect of immune-mediated inflammatory
      response at an early phase after Freund's adjuvant injection on ACTH, GH,
      prolactin and TSH release mechanisms, which was partially sensitive to
      immunosuppression induced by cyclosporine.

PMID- 9588323
TI  - Acute and chronic effects of superior cervical ganglionectomy on in vitro
      mitogenic responses of lymphocytes from submaxillary lymph nodes of pituitary
      grafted rats
AB  - Male rats were grafted an anterior pituitary within breast muscles or received a
      sham operation on day 5 of life. At the 60th day of life, the sympathetic
      denervation of rat submaxillary lymph nodes was achieved by a bilateral
      sympathetic superior cervical ganglionectomy (SCGx; at 15.00 h). Rats were killed
      either 18 h later (acute SCGx) or after 12 days (chronic SCGx) to measure
      lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced cell proliferation in
      submaxillary lymph nodes, submaxillary lymph node cellularity and serum prolactin
      levels. In control rats, acute SCGx significantly augmented LPS or ConA activity
      on lymph cells while chronic SCGx had no effect. In pituitary-grafted rats, acute
      SCGx depressed the mitogenic effect of LPS or ConA whereas chronic SCGx augmented
      it. A global inhibitory effect of surgical stress on submaxillary lymph node
      cellularity was found in rats subjected to SCGx or its sham operation 18 h
      earlier. Serum prolactin levels increased significantly in pituitary-grafted
      rats, particularly in those subjected to chronic SCGx. In pituitary-grafted rats,
      a significant effect of acute SCGx was apparent, with serum prolactin levels
      augmenting about twice in sham-SCGx rats, and to a significantly less extent in
      acute SCGx rats. The results provide further evidence of the immunomodulatory
      role of local sympathetic nerves in submaxillary lymph nodes.

PMID- 9588324
TI  - Cytokine-neurotransmitter interactions in the brain
AB  - The data reviewed in this study show that immune-active molecules, such as
      infectious agents and their components, and cytokines, may induce profound
      alterations in several neurotransmitters in the CNS. The activation of the immune
      system elicits fever, behavioral and neuroendocrine changes and may be involved
      in neuropathological changes occurring in CNS conditions. These effects may be
      achieved through and accounted for by the changes induced in central
      neurotransmitters and in the neuroendocrine system by immune challenges. The
      present review will summarize the available evidence of the reciprocal
      interactions between cytokines and neurotransmitters in the CNS.

PMID- 9588325
TI  - Cytokines and cognitive function in mice
AB  - A bidirectional flow of informations exists between the central nervous system
      and the immune system. Cytokines play a crucial role in this communication and
      exert several neuromodulatory actions. This short review considers some data
      concerning the effects of several cytokines, interleukin (IL)-1, IL-2, IL-6 and
      granulocyte-macrophage colony-stimulating factor on scopolamine-induced amnesia
      for a passive avoidance response, and on hippocampal neurotransmitter amino acid
      levels in mice. We interpret these behavioral and biochemical observations to
      indicate that the cytokine-to-brain communication can result in alterations in
      brain functions.

PMID- 9588326
TI  - Mechanism of action of interleukin-1 in modulating gonadotropin secretion. In
      vivo and in vitro studies
AB  - To obtain further information on the mode of action of interleukin (IL)-1 in
      modulating gonadotropin secretion, a series of in vivo and in vitro studies has
      been performed with the beta-isoform of IL-1. IL-1 beta injected in a lateral
      ventricle of 3-week-castrated female rats resulted in the expected decrease in
      serum levels of gonadotropins luteinizing hormone (LH), and follicle-stimulating
      hormone (FSH), accompanied by a decrease in the number of LH-releasing hormone
      (LHRH) receptors. These results may indicate that the inhibition of gonadotropin
      release may result from a decrease in the number of LHRH pituitary receptors
      either through a direct effect on the pituitary or by modulating the release of
      LHRH from hypothalamic neurons able to induce a reduction in pituitary LHRH
      receptors. In vitro studies using the GT1-1 cell line, which specifically
      produces and secretes LHRH, demonstrated that IL-beta stimulates LHRH release but
      does not influence intracellular levels of LHRH mRNA. These results seem to
      indicate that IL-1 beta may act at several levels of the nervous machinery
      leading to gonadotropin secretion, with a series of effects more complex than
      previously anticipated.

PMID- 9588327
TI  - Melatonin involvement in immunity and cancer
AB  - The most studied endocrine product of the pineal gland, melatonin, has been
      reported to be involved in the feedback between neuroendocrine and immune
      functions and to exert oncostatic action, at least in certain experimental
      conditions. Melatonin seems to be an integral part of the immune system, by
      exerting direct and/or indirect stimulatory effects on both cellular and humoral
      immunity. Likewise, an antitumor activity of melatonin has been shown in several
      experimental models in vivo and in vitro. The means by which melatonin exerts its
      effects on immunity and neoplastic growth have not been elucidated. The different
      putative mechanisms of action of melatonin investigated so far are here briefly
      discussed.

PMID- 9588328
TI  - [Report on quality assurance at unit 34B at the Klinikum Nurnberg].

PMID- 9588330
TI  - [50 years Plegezeitschrift. The news section--"connection with outside"].

PMID- 9588331
TI  - [Spring congress for alternative healing. There is still room for last minute
      decisions].

PMID- 9588332
TI  - [Interest is aimed at hospitals and old age homes. Scientology is preparing to
      capture all of nursing].

PMID- 9588333
TI  - [Summer academy for nurses in Baden-Baden: nursing between marketing and
      humaneness].

PMID- 9588334
TI  - [Reduction of personnel mirrored in the employment advertisements: three out of
      four job offers have been cancelled].

PMID- 9588335
TI  - [Forum for hospital software in Flensburg: electronic data processing and nursing
      -when will it start?].

PMID- 9588336
TI  - [Elsa Brandstrom, on the 50 anniversary of her death. "... on each bed there were
      two patients, often two more..."].

PMID- 9588337
TI  - [Local anesthetics and their use. 2. Central nerve blocks are for intraoperative
      and postoperative analgesia].

PMID- 9588338
TI  - [Care of fever. There are tried alternatives to the standard therapies].

PMID- 9588339
TI  - [Extended nursing measures in daily hospital work: warmth, care and security
      should be transmitted].

PMID- 9588340
TI  - [Evaluation of coworkers. 1. The comparison with other coworkers is useful for
      all].

PMID- 9588341
TI  - [Management ideas and operating suggestions in the social field: coworkers are
      insiders].

PMID- 9588342
TI  - [The Alzheimer Society informs: the diagnosis should be told to the patient
      early].

PMID- 9588343
TI  - [Legislation on working time, stand-by service and work breaks for night care: we
      must find a solution].

PMID- 9588344
TI  - [Backgrounds of the HIV/AIDS epidemic in Africa: traditional pressures and social
      needs are the hidden triggers].

PMID- 9588345
TI  - Immunotoxicological assessment of methyl parathion in female B6C3F1 mice.
AB  - Methyl parathion is a widely used agricultural insecticide, and the recent
      unlicensed use of this compound in homes has led to the evacuation of
      approximately 1100 persons in Mississippi. Although the primary concern in such
      cases of acute exposure is neurotoxicity, a few organophosphorus compounds
      apparently have immunotoxic effects at dosages that do not produce neurotoxic
      symptoms. The purpose of the present study was to determine if this is the case
      for methyl parathion. Female B6C3F1 mice were exposed to methyl parathion by
      gavage, daily for 7, 14, 2 1, or 28 d (at 6 mg/kg/d). Exposure for 14-28 d
      produced significant, dose-responsive inhibition of acetylcholin-esterase (the
      target molecule for methyl parathion-induced neurotoxicity) in brain or plasma,
      indicating that the compound was active. The following immunological parameters
      were evaluated: white blood cell counts and differentials, spleen and thymus
      weight and cellularity, splenic natural killer cell activity, nitrite production
      by peritoneal macrophages following activation in vitro, antibody response to
      sheep erythrocytes in vitro and in vivo, the cytotoxic T lymphocyte response to
      allogeneic tumor cells, and resistance to Streptococcus agalactiae and B16F10
      melanoma cells. Methylparathion at 1 or 3 mg/kg/d significantly increased splenic
      natural killer cell activity. Nitrite production by macrophages was increased in
      mice treated with 1, 3, or 6 mg/kg/d. The antibody response to sheep erythrocytes
      in vitro was significantly suppressed, but the humoral response to sheep
      erythrocytes in vivo was not affected. The cytotoxic T-lymphocyte response to
      allogeneic tumor cells was not significantly affected. Host resistance was not
      significantly decreased. Although it remains possible that immunological
      parameters not tested here may be affected by methyl parathion, the present
      results do not suggest substantial immunotoxic potential for this compound.

PMID- 9588347
TI  - Nickel toxicity to human term placenta: in vitro study on lipid peroxidation.
AB  - It has been reported that nickel (Ni) crosses the human placenta and produces
      teratogenesis and embryotoxicity. In the present study, the effects of nickel on
      human term placentas were investigated. In time-course experiments, placental
      tissue was incubated for 3, 6, 12, or 24 h with 2.5 mM Ni. The viability as
      determined by glucose consumption rate did not show any significant change from 3
      to 12 h, whereas the permeability, lipid peroxidation, and Ni concentration were
      significantly increased compared to the control. In concentration-response
      studies, placental explants were incubated with 0.5, 1.0, 2.5, or 5 mM Ni for 12
      h. The viability did not change significantly, except for 5 mM Ni, but the
      permeability and lipid peroxidation increased markedly in a concentration
      dependent manner. Treatment with ascorbic acid or Zn decreased placental lipid
      peroxidation and permeability induced by Ni, but had no effect on lowering the Ni
      tissue content. Data show that Ni is toxic as evidenced by lipid peroxidative
      damage to placental membrane, and this metabolic change may be responsible for
      decreased placental viability, altered permeability, and potential subsequent
      embryotoxicity.

PMID- 9588346
TI  - Effects of the pesticides carbofuran, chlorpyrifos, dimethoate, lindane,
      triallate, trifluralin, 2,4-D, and pentachlorophenol on the metabolic endocrine
      and reproductive endocrine system in ewes.
AB  - Many pesticides are used in the agricultural environment, and some may have the
      potential to disrupt reproductive or endocrine function. Ewes, in separate groups
      of 6, received orally into their rumen either empty gelatin capsules or capsules
      containing chlorpyrifos (12.5 mg/kg), trifluralin (17.5 mg/kg), lindane (2.5
      mg/kg), or pentachlorophenol (2 mg/kg) 2 times per week for 43 d. Dimethoate (0.2
      mg/kg), carbofuran (0.30 mg/kg), 2,4-dichlorophenoxyacetic acid (10 mg/kg), or
      triallate (5 mg/kg) was given 3 times per week. After 36 d of treatment, blood
      samples were taken every 12 min for 6 h for hormone analysis. Ewes were
      euthanized at the end of the study for necropsy and histopathology. No overt
      signs of toxicity were seen, and body weight was not affected by treatment.
      Carbofuran caused a significant increase in serum concentrations of thyroxine
      compared to control ewes, but all other pesticides, except trifluralin, resulted
      in a marked decrease in thyroxine concentrations. Serum concentrations of
      cortisol were significantly increased by trifluralin and chlorpyrifos.
      Concentrations of insulin in serum were markedly increased in ewes given
      dimethoate, lindane, trifluralin, triallate, and pentachlorophenol, and
      concentrations of estradiol were also significantly increased in ewes given
      lindane and trifluralin. Mean serum concentrations of LH were markedly decreased
      by trifluralin, and basal LH concentrations were significantly decreased by
      lindane, dimethoate, and trifluralin but increased by triallate. Both
      pentachlorophenol and triallate caused a significant increase in severity of
      oviductal intraepithelial cysts in ewes. Data suggest that several currently used
      pesticides could influence serum concentrations of reproductive and metabolic
      hormones, particularly thyroxine, the major secretory product of the thyroid and
      a principal regulator of metabolism.

PMID- 9588348
TI  - A subacute inhalation exposure evaluation of a scrubbing solution used in
      petroleum refineries.
AB  - The potential for subacute toxicity and neurotoxicity of a potassium carbonate
      based scrubbing solution used in petroleum refineries was evaluated in Sprague
      Dawley Crl:CD BR rats. Exposures were to aerosols of a "used" scrubbing solution
      by wholebody inhalation, 6 h/d, for 21 consecutive days at target concentrations
      of 0 (filtered air-control), 0.1, 0.2, or 0.4 mg/L (30 animals/sex/group). A
      functional observation battery (FOB) and locomotor activities tests were
      conducted and monitored. No apparent adverse effects were noted at any exposure
      level as determined by clinical observations, food consumption, hematology, serum
      chemistry, ophthalmologic observations, and gross pathology. Statistically
      significant increases in lung weights were noted at all treatment levels but
      returned to control values upon cessation of exposure except for the 0.4 mg/L
      female group. There were no significant changes in other organ weights.
      Histopathologic findings were restricted to the respiratory tract and
      characterized by minimal to moderate epithelial hyperplasia, epithelial necrosis,
      and cytoplasmic vacuolation at levels I and II of the nasal cavities. Lung
      bronchiolization and alveolar macrophage infiltration were also observed. The
      respiratory-tract findings were considered a local response to the high
      alkalinity of the test material as substantiated by the return to normal upon
      cessation of exposure. Exposure to scrubbing solution had no adverse effect on
      FOB endpoints and locomotor activity evaluations, brain weight and size, and
      neuropathologic examinations. In conclusion, inhalation exposure to a used
      scrubbing solution aerosol for 21 d did not result in any persistent systemic
      toxicity or neurotoxicity in either male or female rats.

PMID- 9588350
TI  - The frequency distribution of the number of ion pairs in irradiated tissue.
AB  - The statistical distribution of the number of ion pairs per ionizing event in a
      small volume simulating a tissue sphere was obtained by applying the Expectation
      Maximization (EM) algorithm to experimental spectra measured by exposing a Rossi
      type spherical proportional counter to gamma radiation. The normalized
      experimental spectrum, r(x), which is the distribution of the number of ion pairs
      per event from both the primary track and the subsequent electron multiplication,
      can be represented as Sum(n) p(n) x f(n,x), where the f(n,x)'s for n = 1, 2, 3,
      ..., n are the normalized spectra for exactly 1, 2, 3, ..., n primary ion pairs
      and are calculated by convoluting the single-electron spectrum. The coefficients
      pn represent the mixing proportions of the spectra corresponding to 1, 2, 3, ...,
      n ion pairs in forming the experimental spectrum. The single-electron spectrum
      used in our calculations is the distribution of the number of ion pairs due to
      the multiplication process, and it is represented in analytical form by the Gamma
      distribution f(1,x) = a x x(b) x e(-cx), where x is energy, usually in eV, and a,
      b and c are constants. The EM algorithm is an iterative procedure for computing
      the maximum likelihood or maximum a posteriori estimates of the mixing
      proportions p(n), which we also refer to as the primary distribution of ion pairs
      in a microscopic spherical tissue-equivalent volume. The experimental and primary
      spectra are presented for simulated tissue spheres ranging from 0.25 to 8 microm
      in diameter exposed to 60Co gamma radiation.

PMID- 9588349
TI  - Increased apoptosis, changes in intracellular Ca2+, and functional alterations in
      lymphocytes and macrophages after in vitro exposure to static magnetic field.
AB  - Electromagnetic-related alteration of cellular functions is well documented for
      extremely low-frequency low-energy pulsing electromagnetic fields (ELF-EMF). In
      this study we examined the in vitro effects of static magnetic fields (SMF) on
      the cellular immune parameters of the C57BI/6 murine macrophages, spleen
      lymphocytes, and thymic cells. The cells were exposed in vitro for 24 h at 37
      degrees C, 5% CO2, to 250-1500 G SMF. Exposure to the SMF resulted in the
      decreased phagocytic uptake of fluorescent latex microspheres, which was
      accompanied by an increased intracellular Ca2+ level in macrophages. Exposure to
      SMF decreased mitogenic responses in lymphocytes, as determined by incorporation
      of [3H]thymidine into the cells. This was associated with the increased Ca2+
      influx in concanavalin A-stimulated lymphocytes. Furthermore, exposure to SMF
      produced markedly increased apoptosis of thymic cells, as determined by flow
      cytometry. Overall, in vitro exposure of immunocompetent cells to 250-1500 G SMF
      altered several functional parameters of C57BI/6 murine macrophages, thymocytes,
      and spleen lymphocytes.

PMID- 9588351
TI  - Ab initio electronic structure calculation of a new gene system using the
      negative factor counting method.
AB  - We report a calculation of the electronic structure (density of states and
      molecular orbitals) of a new gene system-the plasmid shuttle vector pCRR1
      performed at the ab initio Hartree-Fock level. To deal with the aperiodicity of
      the biopolymer, a vectorized version of a negative factor counting (NFC) program
      has been implemented. With this efficient tool, DNA molecules of up to 100
      deoxynucleotides (approximately 10,000 basis functions at the ab initio level)
      can be calculated routinely. In our calculation the base sequence of the plasmid
      is explicitly taken into account and a standard helical structure is assumed.
      Minimum as well as 6-31G basis sets are used in the calculation, and solvation
      effects are explicitly included. The calculation shows that solvation does not
      have a significant effect on the electronic structure of the biopolymer. It is
      found that the frontier orbitals (HOMO and LUMO) are highly localized on the
      bases. The interpretation of this result in terms of the frontier molecular
      orbital theory is that the attack of radiation-induced radicals is mainly on the
      base moieties.

PMID- 9588352
TI  - Modification of the reductive pathway in gamma-irradiated DNA by electron
      scavengers: targeting the sugar-phosphate backbone.
AB  - Several electron scavengers that irreversibly form potential hydrogen-abstracting
      species upon one-electron reduction have been tested as agents for conversion of
      reductive damage to DNA bases into damage to the sugar-phosphate backbone.
      Electron spin resonance spectroscopy is employed to follow the production of
      radicals and transformations after irradiation. The scavengers tested included
      neutral (acrylamide, iodoacetamide) and cationic [triphenylsulfonium (Ph3S+),
      o,o'-diphenylenebromonium (DPB) and o,o'-diphenyleneiodonium (DPI)] compounds.
      Modification of reductive radiation damage in DNA is found to occur by scavenging
      of initial mobile electrons at low temperatures as well as thermally activated
      electron transfer from DNA electron-gain centers upon annealing. Electron
      transfer from the bases to hydrogen-bonded acrylamide has the smallest activation
      energy among other scavengers but produces a secondary alkyl radical incapable of
      abstracting hydrogen from the sugar-phosphate backbone. A primary alkyl radical
      generated from iodoacetamide has been shown to abstract preferentially from the
      thymine methyl group but not from deoxyribose moieties. Aryl radicals generated
      from aromatic onium salts such as Ph3S+, and especially DPI and DPB, are found to
      be the agents which best abstract hydrogen atoms from the deoxyribose portion of
      DNA. The use of DPB and DPI as radiation modifiers allows the elimination of
      undesirable side reactions of aryl radicals and through hydrogen abstraction
      results in high yields of a species identified as the DNA C1'. sugar radical. The
      second reaction pathway found for DPI and DPB in DNA is addition of an aryl
      radical to the thymine 5,6 double bond. Cysteamine is shown to preferentially
      eliminate sugar radicals upon annealing and to have little impact on the thermal
      stability of the thymine adduct radical.

PMID- 9588353
TI  - Tandem lesions and other products in X-irradiated DNA oligomers.
AB  - Free radicals interact with DNA bases to produce secondary radicals. The
      secondary radicals are reactive species and tend to interact with neighboring
      bases, resulting in DNA lesions with two adjacent modified bases. In this study
      the DNA oligomers d(CpApTpG) and d(CpGpTpA) were exposed to free radicals
      generated in anoxic aqueous solution by X irradiation. Four new lesions were
      identified in which adjacent guanine and pyrimidine bases are covalently bonded.
      One of the tandem lesions formed in d(CpGpTpA) has the C5 carbon atom of cytosine
      covalently bonded to the C8 carbon atom of guanine. Interestingly, the same bond
      is formed between the terminal bases in d(CpApTpG), resulting in a cyclized
      molecule.

PMID- 9588354
TI  - Wortmannin inhibits repair of DNA double-strand breaks in irradiated normal human
      cells.
AB  - Wortmannin, a specific inhibitor of PI-3 kinase, was recently found to be an
      effective radiosensitizer in cells of various human and murine cell lines.
      Another study indicated that wortmannin inhibited repair of DNA double-strand
      breaks (DSBs) in irradiated Chinese hamster ovary cells using the neutral elution
      assay. To further clarify the mechanism behind radiosensitization by wortmannin,
      we have studied DSB repair in gamma-irradiated normal human fibroblasts using
      pulsed-field gel electrophoresis. The rejoining of DSBs in irradiated cells was
      significantly inhibited when 20 microM or more of wortmannin was added to the
      cells. The colony formation assay in cultures treated with wortmannin showed that
      the radiosensitization occurred in a manner that was dependent on the drug
      concentration. However, significant sensitization was observed only with a
      concentration of wortmannin of 20 microM or higher, reflecting the results of DSB
      rejoining studies. No marked reduction in plating efficiencies was observed for
      cells treated with wortmannin alone. The studies of the levels of expression of
      DNA-dependent protein kinase (DNA-PK) indicated that, while there were no
      significant changes in expression of Ku protein, the expression of the DNA-PK
      catalytic subunit (DNA-PKcs) was reduced markedly in cultures treated with
      wortmannin using an antibody against the C-terminus region of DNA-PKcs. In
      addition, no reduction in the levels of expression of DNA-PKcs was observed in
      cells treated with wortmannin using an antibody which recognizes a mid-region of
      this large protein. These results together with those of related studies suggest
      that wortmannin radiosensitizes normal human cells by inhibiting DSB repair and
      that this inhibition is a consequence of an inactivation of kinase activity
      and/or a structural change caused by binding of wortmannin to the C-terminus
      region of DNA-PKcs.

PMID- 9588355
TI  - Rejoining and misrejoining of radiation-induced chromatin breaks. IV. Charged
      particles.
AB  - We have recently reported the kinetics of chromosome rejoining and exchange
      formation in human lymphocytes exposed to gamma rays using the techniques of
      fluorescence in situ hybridization (FISH) and premature chromosome condensation
      (PCC). In this paper, we have extended previous measurements to cells exposed to
      charged particles. Our goal was to determine differences in chromatin break
      rejoining and misrejoining after exposure to low- and high-linear energy transfer
      (LET) radiation. Cells were irradiated with hydrogen, neon, carbon or iron ions
      in the LET range 0.3-140 keV/microm and were incubated at 37 degrees C for
      various times after exposure. Little difference was observed in the yield of
      early prematurely condensed chromosome breaks for the different ions. The
      kinetics of break rejoining was exponential for all ions and had similar time
      constants, but the residual level of unrejoined breaks after prolonged incubation
      was higher for high-LET radiation. The kinetics of exchange formation was also
      similar for the different ions, but the yield of chromosome interchanges measured
      soon after exposure was higher for high-LET particles, suggesting that a higher
      fraction of DNA breaks are misrejoined quickly. On the other hand, the rate of
      formation of complete exchanges was slightly lower for densely ionizing
      radiation. The ratios between the yields of different types of aberrations
      observed at 10 h postirradiation in prematurely condensed chromosome preparations
      were dependent on LET. We found significant differences between the yields of
      aberrations measured in interphase (after repair) and metaphase for densely
      ionizing radiation. This difference might be caused by prolonged mitotic delay
      and/or interphase death. Overall, the results point out significant differences
      between low- and high-LET radiation for the formation of chromosome aberrations.

PMID- 9588357
TI  - Changes in phenotypic expression of osteoblasts after X irradiation.
AB  - Changes in the phenotypic expression of osteoblasts after X irradiation were
      investigated. Osteoblast-like MC3T3-E1 cells at the actively proliferating,
      confluent and postproliferation stages were subjected to 10 Gy X irradiation.
      Irradiation at the confluent stage enhanced accumulation of type I collagen
      normalized to the DNA content. Irradiation at all stages down-regulated the
      expression of osteocalcin, but the levels of osteopontin and osteonectin mRNAs
      were unchanged from the control level. After irradiation at the later stages, the
      time-dependent increase in alkaline phosphatase activity per cell exceeded that
      in the control cells. The localization of alkaline phosphatase-positive cells was
      concordant with that of calcification. In addition, the quality of the calcium
      deposits was found to be similar to that in control cells as determined by energy
      dispersive spectrometry and the ratio of calcium to phosphorus, even if the cells
      were not exactly the same morphologically. The changes in phenotypic expression
      observed here are closely related to the enhancement of calcification observed in
      a previous study.

PMID- 9588356
TI  - Higher-order chromatin structure-dependent repair of DNA double-strand breaks:
      involvement of the V(D)J recombination double-strand break repair pathway.
AB  - Repair of DNA double-strand breaks (DSBs) is linked to the V(D)J recombination
      pathway through investigations of radiation-sensitive mutants. Here we report a
      possible association between the distribution of DSBs within higher-order
      chromatin structures and this pathway. Both murine severe combined
      immunodeficient (SCID) and Chinese hamster XR-1 cells exhibit defective DNA DSB
      repair and defective V(D)J recombination. The DSB repair defect is not complete,
      with only a subset of slowly repairing lesions affected by the mutations in these
      cell lines. We used a modified neutral filter elution procedure which retained
      elements of higher-order chromatin structures, namely nuclear matrix-DNA
      interactions. X-ray-induced DSBs that occurred as multiples within looped DNA
      structures were nonrepairable in SCID and XR-1 cells. In contrast, these lesions
      were repaired in radioresistant wild-type cells. Cell lines complemented with
      human DNA containing the respective complementing genes (XRCC7 and XRCC4) showed
      an increased rate of DSB repair. These results agree with previous findings with
      xrs5 cells (a member of the XRCC5 group). Xrs5 cells are defective for the Ku p80
      subunit of the V(D)J recombination complex and show repair and V(D)J
      recombination defects similar to those of SCID and XR-1 cells.

PMID- 9588359
TI  - Radiation-induced muscle damage in rats after fractionated high-dose irradiation.
AB  - Muscle damage in the legs of male Wistar rats after exposure to high-dose
      radiation was evaluated by observations of biopsied tissue made with light and
      transmission electron microscopy. Both legs of about 40 mature male Wistar rats
      were exposed to 80 Gy 6 MV X rays from a linear accelerator given in 40 fractions
      of 2 Gy. At intervals starting from the first day to 12 months after irradiation,
      serial muscle biopsies were obtained by sacrificing the rats on different days
      according to the experimental design. The irradiated gastrocnemius muscle
      displayed a progressive structural change that began immediately after the
      completion of the exposures. Morphological changes in irradiated muscles were
      characterized by hemorrhage, lymphocytic infiltration and obvious vascular
      destruction. Increased amounts of collagen between the muscle fibers were present
      even at 12 months after irradiation. There were significant changes in the
      number, size and structure of mitochondria in the muscle cells from the first day
      until 1 year after irradiation. Even 12 months after the final exposure, no
      recovery of muscle tissue was seen by light and transmission electron microscopy.

PMID- 9588358
TI  - Unlike tenascin-X, tenascin-C is highly up-regulated in pig cutaneous and
      underlying muscle tissue developing fibrosis after necrosis induced by very high
      dose gamma radiation.
AB  - Fibrosis is characterized by proliferation of fibroblasts and deposition of
      extracellular matrix (ECM). As alterations in the composition of ECM may account
      for its chronic extension, we studied the expression of the tenascin-C (TN-C) and
      tenascin-X (TN-X) ECM glycoproteins in our pig model of the effects of accidental
      exposures to radiation, in which cutaneous and muscle fibrosis developed after
      the induction of necrosis after a high single dose (160 Gy at the skin surface)
      of gamma rays. We found that, in the healed fibrotic dermis and underlying muscle
      fibrosis, the amount of TN-C mRNA was increased up to 18- and 39-fold,
      respectively, compared to normal dermis, whereas the level of TN-X mRNA remained
      almost unchanged. In analyses by Western blotting, the two main TN-C isoforms of
      235-240 and 190-200 kDa increased up to 45- and 105-fold in fibrotic tissues,
      respectively. The large isoform was expressed more strongly than the smaller,
      although in healed fibrotic scar tissues their ratio was lower in protein than in
      RNA. Compared to unirradiated skin, an immunohistological study revealed stronger
      TN-C staining at the dermo-epidermal junction and in areas of remodeling in
      healed skin. An intense extracellular staining was observed around myofibroblasts
      in muscle fibrosis. Therefore, the gene encoding TN-C is highly up-regulated in
      fibrotic tissues, and mechanisms regulating the levels of TN-C variants occur at
      both the RNA and protein levels. Each isoform might play a distinct role in the
      chronic activation of fibrosis by differentially regulating mechanisms like cell
      adhesion, migration or proliferation.

PMID- 9588360
TI  - An interspecies prediction of the risk of radiation-induced mortality.
AB  - Mortality data for B6CF1 mice exposed to 60Co gamma rays for the duration of life
      were used to make quantitative predictions of age-specific mortality observed in
      comparably exposed beagles. Simple Kaplan-Meier survival curves for the beagles
      and their 95% confidence intervals were computed for each dose-rate group
      observed. A dose-response equation was estimated from the mortality data for mice
      using a proportional hazard model. The dose-response model for mice was then used
      to generate predicted survivorship curves at dose rates that would recreate the
      dose burdens observed in the beagle at comparable points within the life span of
      the two organisms. When these predicted survivorship curves were scaled to adjust
      for species differences in the life span of control animals, the predictions for
      the mouse fell within the confidence intervals observed for the beagle. The
      successful interspecies extrapolation of age-specific mortality risks for species
      as different as the mouse and dog enhances both the value of studies involving
      laboratory animals and the potential relevance of the animal studies to the
      prediction of health effects in humans.

PMID- 9588361
TI  - Cancer predisposition, radiosensitivity and the risk of radiation-induced
      cancers. IV. Prediction of risks in relatives of cancer-predisposed individuals.
AB  - Individuals carrying cancer-predisposing germline mutations are known to be at a
      higher risk for cancers than those who do not carry them. This is also true of
      their biological relatives because they have a higher probability of being
      carriers of such mutant genes than unrelated individuals in the population.
      Further, there are now sufficient grounds for assuming that cancer-predisposed
      individuals may also be at a higher risk for cancers induced by ionizing
      radiation. In our earlier work, we examined the impact of this heterogeneity
      (with respect to cancer predisposition and radiosensitivity differentials) on
      risks of radiation-induced cancer at the population level. This paper is focused
      on the question of risks of radiation-induced cancer in relatives of cancer
      predisposed individuals. Using an autosomal dominant model of cancer
      predisposition and radiosensitivity developed earlier and applying it to breast
      cancer risks associated with mutations in the BRCA1 gene, we show that: (1) The
      risk ratio (i.e. the ratio of risk of radiation-induced cancer in relatives to
      that in unrelated individuals) in the population increases with the degree of
      biological relatedness of the relative, being higher for close than for distant
      relatives; incomplete penetrance of the mutant gene "dilutes" this risk ratio.
      (2) The proportion of excess radiation-induced cancers in relatives (i.e. the
      attributable fraction) is higher than in unrelated individuals. (3) In relatives,
      the proportion of excess cancers due to radiosensitivity differentials alone
      depends on the strength of predisposition, the radiosensitivity differentials
      assumed, the radiation dose, the proportion of cancers due to predisposition, the
      mutant gene frequency and the penetrance of the mutant gene. This is in contrast
      to the situation for unrelated individuals, for whom the above-mentioned
      proportion is dependent on the first three but not on the last three of these
      factors. Further, even when the proportion of excess cancers is small, most of it
      is due to radiosensitivity differential alone both in unrelated individuals and
      in relatives. (4) For values of predisposition strength and radiosensitivity
      differential <10, even when the estimated frequency of a mutant BRCA1 gene is
      0.0047 and the proportion of breast cancers due to these mutations is 38% (as is
      the case for Ashkenazi Jewish women under age 30), the increase in breast cancer
      risks is only marginal even for first-degree relatives. (5) These findings
      support the conclusion that increases in radiation risks to relatives (compared
      to those in unrelated individuals), to be detectable epidemiologically, will
      occur only when the mutant alleles are common and the strength of predisposition
      and radiosensitivity differentials are conjointly dramatic.

PMID- 9588362
TI  - Phase transitions in the growth of C3H 10T1/2 cells.
AB  - In systems used to express transformation using focus formation as the end point,
      nontransformed cells generally express a down-regulation of cell growth and
      division made evident by the formation of a monolayer of cells that completely
      covers the growth surface. In C3H 10T1/2 cells, down-regulation is thought to be
      progressively effected principally by cell-to-cell communication via gap
      junctions. Starting with a sparse population in asynchronous growth--e.g.
      containing cells in all phases of the growth cycle--as the area density
      increases, cells are progressively lost from the distribution in the order M
      phase, G2 phase, S phase and G1 phase, leading to the accumulation of viable
      cells out of cycle in so-called G0 phase. We have measured the progressive phase
      transitions as a function of inoculum size and time. The influence of a promoter
      and an antipromoter was also examined as well as the expression of the
      cyclin/cyclin-dependent kinase inhibitors p21Waf1/Cip1 and p27Kip1 as the cells
      grew into confluence. Using cells synchronized in mitosis, we found that with
      increasing cell density the expression of p27 increased and concomitantly p21
      decreased.

PMID- 9588364
TI  - Low-dose radiation sensitivity and a subpopulation of sensitive cells.

PMID- 9588363
TI  - Induction of an adaptive response against spontaneous neoplastic transformation
      in vitro by low-dose gamma radiation.
AB  - An adaptive response against spontaneous neoplastic transformation in vitro
      induced by low-dose gamma radiation has recently been reported using a clone of
      C3H 10T1/2 cells with a predisposition toward spontaneous transformation (Azzam
      et al., Radiat. Res. 146, 369-370, 1996). To test the generality of this
      observation, the HeLa x skin fibroblast human hybrid cell system was used to look
      for such an adaptive response using a similar experimental protocol. In the
      experimental protocol used, the frequency of neoplastic transformation of
      unirradiated cultures (Arm A) was compared to that of cultures which had been
      irradiated with 1 cGy of gamma radiation and either plated immediately (Arm B) or
      held for 24 h at 37 degrees C prior to plating (Arm C) for assay of neoplastic
      transformation. The pooled data from four separate experiments demonstrated a
      significantly reduced transformation frequency for Arm C compared to Arms A and
      B. This is indicative of an adaptive response in the case of postirradiation
      holding, in agreement with the earlier study using C3H 10T1/2 cells. However,
      with the exception of one experiment, the existence of the adaptive response was
      not clear on the basis of analysis of individual experiments. This points out the
      importance of sample size when looking at low-dose effects that are close in
      magnitude to the inherent variations in spontaneous transformation frequency.

PMID- 9588365
TI  - The cancer risk from low-level radiation.

PMID- 9588366
TI  - Identifying nursing home residents at risk for falling.
AB  - OBJECTIVES: To develop a fall risk model that can be used to identify
      prospectively nursing home residents at risk for falling. The secondary objective
      was to determine whether the nursing home environment independently influenced
      the development of falls. DESIGN: A prospective study involving 1 year of follow
      up. SETTING: Two hundred seventy-two nursing homes in the state of Washington.
      PARTICIPANTS: A total of 18,855 residents who had a baseline assessment in 1991
      and a follow-up assessment within the subsequent year. MEASUREMENTS: Baseline
      Minimum Data Set items that could be potential risk factors for falling were
      considered as independent variables. The dependent variable was whether the
      resident fell as reported at the follow-up assessment. We estimated the extrinsic
      risk attributable to particular nursing home environments by calculating the
      annual fall rate in each nursing home and grouping them into tertiles of fall
      risk according to these rates. RESULTS: Factors associated independently with
      falling were fall history, wandering behavior, use of a cane or walker,
      deterioration of activities of daily living performance, age greater than 87
      years, unsteady gait, transfer independence, wheelchair independence, and male
      gender. Nursing home residents with a fall history were more than three times as
      likely to fall during the follow-up period than residents without a fall history.
      Residents in homes with the highest tertile of fall rates were more than twice as
      likely to fall compared with residents of homes in the lowest tertile,
      independent of resident-specific risk factors. CONCLUSIONS: Fall history was
      identified as the strongest risk factor associated with subsequent falls and
      accounted for the vast majority of the predictive strength of the model. We
      recommend that fall history be used as an initial screener for determining
      eligibility for fall intervention efforts. Studies are needed to determine the
      facility characteristics that contribute to fall risk, independent of resident
      specific risk factors.

PMID- 9588367
TI  - A preliminary assessment of the medical and functional factors associated with
      vehicle crashes by older adults.
AB  - OBJECTIVES: To examine associations between medical and functional variables and
      at-fault car crashes in a cohort of older drivers. DESIGN: A case-control study.
      SETTING: A tertiary care medical center. PARTICIPANTS: Older drivers (ages 55-90
      years) residing in Jefferson County, Alabama (n = 174). Cases were drivers who
      had at least one at-fault crash in the previous 6 years; controls were crash-free
      during the same period. MEASUREMENTS: Self-reported medical conditions, reported
      and observed functional measures, and urinary drug screens. The occurrence of one
      or more at-fault car crashes in the 6 years preceding the 1991 assessment date
      represented the outcome measure. RESULTS: Ninety-nine older drivers experienced
      between one and seven at-fault vehicle crashes during the period 1985 through
      1991, whereas 75 drivers did not. Logistic regression models indicated that the
      following variables were independently associated with crash involvement: A 40%
      or greater reduction in the useful field of view (OR = 6.1; 95% CI, 2.9 to 12.7;
      P < 0.001), black race (OR = 6.6; 95% CI, 1.7 to 26.2; P = .007), a history of
      falling in the previous 2 years (OR = 2.6; CI, 1.1 to 6.1; P = .025), and not
      taking a beta-blocking drug (OR = 4.3; CI, 1.2 to 15.0; P = .023). CONCLUSIONS:
      Functional assessments, such as a comprehensive test of visual processing, a
      falls history, and a review of current medications may be of greater relevance
      than specific medical conditions in the identification of older at-risk drivers.
      If prospective studies determine that falling and crashing share risk factors, a
      unified approach to the prevention of these mobility disorders could result. The
      finding of an independent association of black race with at-fault crashing is in
      need of further clarification because of the low representation of black drivers
      in this sample.

PMID- 9588368
TI  - Development of a test battery to identify older drivers at risk for self-reported
      adverse driving events.
AB  - OBJECTIVES: The purposes of this study were (1) to develop a battery of tests
      that assessed a wide range of functional abilities relevant to driving yet could
      be performed in a clinician's office and (2) to determine which of these tests
      were most closely associated with self-reported adverse driving events. DESIGN: A
      cohort study. SETTING: An urban community. PARTICIPANTS: Participants were drawn
      from the Project Safety cohort, a probability sample of noninstitutionalized
      older persons in New Haven, Connecticut, initiated in 1989. The current study
      included surviving, active drivers in the cohort (N=125). MEASURES: The test
      battery assessed visual, cognitive, and physical abilities potentially relevant
      to driving, and was administered in participants' homes by trained interviewers
      between October 1994 and July 1995. Outcome measures included the self-report of
      a crash, moving violation, or being stopped by police in any Project Safety
      interview since the inception of the cohort. Analyses compared performance on the
      elements of the test battery with participants' histories of adverse driving
      events. RESULTS: Of the 125 drivers, 50 (40%) had reported an adverse event in a
      mean period of 5.76 (+/-.25) years before the current interview. The elements of
      the test battery independently associated with a history of events, adjusting for
      driving frequency, included near visual acuity worse than 20/40 (adjusted odds
      ratio 11.90), limited neck rotation (OR 6.10), and poor performance on a test of
      visual attention, the number cancellation task (OR 3.00). The resulting
      regression equation yielded a sensitivity of 80%, a specificity of 55%, and an
      area under the curve of .75 by receiver operating characteristic analysis.
      CONCLUSION: These findings suggest it may be possible to identify individuals
      potentially at risk for self-reported adverse driving events using simple tests
      of functional ability. If validated, such an approach could be used to identify
      individuals who need a more detailed assessment of functional abilities to
      determine the severity and etiology of impairments, and their effect on driving
      performance, as well as possible interventions to correct or compensate for the
      impairments.

PMID- 9588369
TI  - Low airloss hydrotherapy versus standard care for incontinent hospitalized
      patients.
AB  - OBJECTIVE: To determine whether low airloss hydrotherapy reduces the incidence of
      new skin lesions associated with incontinence in hospitalized patients and
      results in more rapid healing of existing pressure sores compared with standard
      care. To assess subjectively patient and nursing satisfaction related to using
      low airloss hydrotherapy beds. DESIGN: Randomized, prospective, unblinded study.
      SETTING: Acute and chronic hospital wards. PARTICIPANTS: A total of 116 newly
      admitted, incontinent, hospitalized patients with and without existing pressure
      sores. INTERVENTION: Low airloss hydrotherapy compared with treatment on hospital
      beds and mattresses ordered by the patient's attending physician. MEASUREMENTS:
      Incidence rates of new skin lesion development, e.g., pressure sores,
      candidiasis, and chemical irritation; improvement in existing pressure sore size,
      volume, and status; subjective assessment of patient and nursing satisfaction.
      RESULTS: Possible hypothermia was identified in two patients during the first
      week of the study, and patient and nursing dissatisfaction with low airloss
      hydrotherapy remained high throughout the first months of the study. Therefore,
      two major modifications in the initial protocol were made: (1) increased patient
      temperature monitoring for hypothermia was initiated in Week 2 of the study and
      (2) increased staff resources for in-service training on bed use began in Week 18
      of the study. After the latter change, 58 subjects were randomized to low airloss
      hydrotherapy and 58 to standard care. Subjects were old (median age > or = 80
      years), and almost all were bedbound or nonambulatory. The median (range) length
      of follow-up for subjects in the treatment group was significantly shorter than
      for those in the control group (4 (1-60) days versus 6 (1-62) days, respectively,
      P = .017) because there were more dropouts from the treatment group (24 (36%) of
      58 versus 2 (3%) of 58, P = .0001). The major reasons dropout occurred were
      patient or family dissatisfaction (12 (21%)), new or worsened skin lesions
      thought to be related to bed use (4 (7%)), and hypothermia < 97 degrees F (4
      (7%)). The total cumulative incidence of new truncal skin lesions within 9 days
      of enrollment was greater in the treatment than in the control group (48% versus
      14%, respectively, P < 0.01). Too few patients with existing pressure sores were
      treated for too short a period of time to assess the effect of low airloss
      hydrotherapy on pressure sore healing. Because only 10 patients treated on low
      airloss hydrotherapy beds were able to complete satisfaction surveys
      meaningfully, interpretation of these data is difficult. Only nine (21%) of 44
      nurses subjectively reported overall satisfaction using the low airloss
      hydrotherapy bed. CONCLUSIONS: This study shows the value of a rigorously
      designed clinically based evaluation of a new product developed for older
      patients. The results of the study led to re-engineering of the prototype low
      airloss hydrotherapy bed as well as a change in marketing strategy. Studies of
      products targeted to the prevention and treatment of pressure sores in older
      patients should be undertaken before generalized marketing begins.

PMID- 9588370
TI  - The sequelae of hospitalization for ischemic stroke among older adults.
AB  - OBJECTIVES: To estimate the independent effect of hospitalization for ischemic
      stroke on change in functional status, subsequent hospitalization, and mortality.
      DESIGN: Secondary analysis of the nationally representative Longitudinal Study on
      Aging. Baseline (1984) interview data were linked to Medicare hospitalization and
      death records for 1984-1991 and to functional status reports at three biennial
      follow-ups. SETTING: In-person and telephone interviews were conducted.
      PARTICIPANTS: A total of 6071 noninstitutionalized respondents 70 years old or
      older at baseline. MEASUREMENTS: Hospitalization for ischemic stroke was defined
      as having one or more episodes with primary discharge ICD9-CM codes of 433.0
      434.9, 436, and 437.0-437.1. Two reference groups were used: those who were
      hospitalized for something other than stroke, and those who were not hospitalized
      at all. The statistical methods employed were multivariable proportional hazards,
      logistic, and linear regression. RESULTS: The adjusted hazards ratio for having a
      primary hospital discharge diagnosis of ischemic stroke on mortality was 7.57
      (CI95% = 6.47 to 8.85) versus 3.67 (CI95% = 3.28 to 4.10) for having been
      hospitalized for something other than stroke (both compared with the reference
      category of those not hospitalized at all). The adjusted odds ratio for having
      any subsequent hospitalization associated with having a primary hospital
      discharge diagnosis of ischemic stroke (compared with having been hospitalized
      for something other than stroke) was not significantly elevated (AOR = 1.16;
      CI95% = .94 to 1.42). However, the percent increases in the subsequent number of
      hospital episodes, total charges, and total length of stay for those who were
      hospitalized for ischemic stroke relative to those hospitalized for something
      other than stroke were significant (P < .001), and ranged from 16.3 to 39.0%.
      Hospitalization for ischemic stroke was also related significantly to greater
      increases in the regression-adjusted mean number of instrumental activities of
      daily living and lower body function limitations at follow-up. CONCLUSION:
      Hospitalization for ischemic stroke among older adults substantially increases
      the risk of subsequent mortality, the volume of hospital resource consumption,
      and greater functional decline, even when compared with hospitalization for
      something other than stroke. Therefore, greater attention to the prevention and
      management of ischemic stroke is needed.

PMID- 9588371
TI  - Relation between intellectual dysfunctioning and mortality in community-residing
      older people.
AB  - OBJECTIVE: To examine the relationship between intellectual dysfunctioning and
      mortality in a community-residing older population. DESIGN: Of the 1473 randomly
      selected people aged 65 years and older living in Settsu, Osaka Prefecture, in
      October 1992, 1405 were contacted. Data for assessment of intellectual
      dysfunctioning were obtained from 1383 people (98.4%), who constituted the study
      cohort. Follow-up for 42 months was completed for 1300 subjects (94.0%; 1117
      living, 183 deceased). MEASURES: Data on general health status, history of health
      management, psychosocial conditions, and intellectual dysfunctioning were
      collected by means of interviews during home visits at the time of enrollment.
      Intellectual dysfunctioning was determined with the assessment instrument
      developed by the Social Survey Division of the Office of Population Censuses
      (OPCS) in Great Britain. RESULTS: The Kaplan-Meier analysis indicated that the
      estimated survival rates for men and women decreased with a decline in
      intellectual function in two age groups: 65 to 74 and 75 years and older. For
      both sexes, the log rank test showed that the curves among the four groups based
      on intellectual dysfunctioning (intact, mild, moderate, and severe) achieved
      statistical significance for the age group of 75 years and older. For both age
      groups and each of the levels of intellectual dysfunctioning, the estimated
      survival rate for men was lower than that for women. Application of the Cox
      proportional hazards model resulted in unadjusted hazard ratios of mild,
      moderate, and severe intellectual dysfunctioning for mortality of 1.68, 2.44, and
      5.37, respectively. Multivariate analysis on the other hand, yielded adjusted
      hazard ratios of mild, moderate, and severe intellectual dysfunctioning of 1.19,
      1.12, and 1.74, respectively, leaving severe dysfunctioning as the only
      statistically significant factor associated with mortality. Other factors such as
      sex, age, general health status, history of management, and psychosocial
      conditions were controlled. CONCLUSION: Intellectual dysfunctioning, as measured
      by an assessment instrument developed by OPCS, represents an increased risk
      factor for mortality among community-residing older people.

PMID- 9588372
TI  - Executive cognitive abilities and functional status among community-dwelling
      older persons in the San Luis Valley Health and Aging Study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the contribution of the
      executive cognitive functions to self-reported and observed performance of
      activities of daily living and instrumental activities of daily living. DESIGN:
      These data were collected as part of a cross-sectional survey of community
      dwelling older persons, using statistical sampling, in a two-county area of
      southern Colorado. SETTING: Participants were interviewed and administered
      measures of general cognition, depression, executive functioning, and performance
      of self-care and instrumental activities, either in their homes or at the study
      clinic. PARTICIPANTS: A total of 1158 community-dwelling persons between the ages
      of 60 and 99 participated. Of these, 657 were female, 501 were male, 637 were
      Hispanic, and 521 were non-Hispanic whites. MEASUREMENTS: Subjects were
      administered the Mini-Mental State Exam (MMSE), a measure of executive
      functioning (the Behavioral Dyscontrol Scale), the Center for Epidemiologic
      Studies Depression scale (CES-D), and the Structured Assessment of Independent
      Living Skills (SAILS, a measure of observed performance of daily tasks). They
      also were interviewed regarding their reported ADL and IADL status using measures
      from the Longitudinal Study on Aging. RESULTS: Both general mental status and
      executive functioning demonstrated statistically significant univariate
      associations with all seven functional status measures (both self-report and
      observed performance). In a series of ordinary least squares regression models,
      executive functioning was a predictor for self-reported ADLs and observed
      performance of complex IADL tasks such as managing money and medications. Mental
      status did not predict self-reported functioning but was a predictor of observed
      performance. Depression was a significant variable for self-report measures but
      not for observed performance. Executive functioning and general mental status
      demonstrated some degree of independence from one another. CONCLUSION: Executive
      functioning is an important determinant of functional status for both self
      reported and observed ADLs and IADLs and should be assessed routinely when
      evaluating the mental status and functional abilities of older people. These
      results replicate and extend previous research on executive functioning among
      older persons by examining these factors in a large bi-ethnic community sample.

PMID- 9588373
TI  - Absence of vascular dementia in an autopsy series from a dementia clinic.
AB  - OBJECTIVE: The role of cerebrovascular disease in dementia in older people has
      been the subject of controversy. This study was undertaken to examine the
      prevalence of vascular disease in a prospective autopsy series of patients with
      clinically diagnosed dementia. DESIGN: Structured review of clinical and
      neuropathological examinations. Clinical diagnoses were assigned in accordance
      with the recommendations of the NINCDS/ADRDA consensus panel. Neuropathological
      examinations were performed at an academic neuropathology service using published
      consensus criteria for the diagnosis of Alzheimer's disease and other forms of
      dementia. SETTING: A subspecialty, outpatient dementia clinic in a university
      affiliated suburban American hospital. PARTICIPANTS: Eighty-seven unselected
      patients coming to autopsy who had undergone clinical dementia evaluation.
      RESULTS: Dementia could not be attributed to the effects of cerebrovascular
      disease alone in any of the 87 patients coming to autopsy. Seventy-six (87%) of
      the patients were found to have Alzheimer's disease (AD), 44 had AD alone, and 32
      had AD in combination with cerebrovascular disease (CVD). All of the patients
      with signs of CVD at autopsy were also found to have some concomitant
      neurodegenerative disease. The absence of patients in whom vascular dementia
      could be diagnosed at neuropathology was not the result of recruitment bias.
      CONCLUSION: Clinicians should maintain a high index of suspicion of AD or other
      neurodegenerative process in older patients whose presenting complaint is
      dementia, even in the presence of well documented cerebrovascular disease.

PMID- 9588374
TI  - Acceptability to patients of a home hospital.
AB  - OBJECTIVE: To examine the acceptability to older patients of receiving care in
      the home for acute medical conditions that require hospital level care by current
      standards. DESIGN: Interviews with patients during hospitalization regarding
      their views of a hypothetical "home hospital." PARTICIPANTS: Patients (n = 87)
      admitted to a community-based academic medical center with a primary diagnosis of
      pneumonia, congestive heart failure, or chronic obstructive airway disease, their
      nurses (n = 111), and resident physicians (67). MEASUREMENTS: A questionnaire was
      developed to measure several domains of acceptability and expectations for care.
      RESULTS: A majority of patients agreed that treatment in a home hospital would be
      more comfortable compared with treatment in a hospital (78.5%), would be less
      likely to result in an infection (62.5%), and would not be a burden to their
      family (71.8%). There was less certainty that medical care at home can be as good
      as in the hospital (56.9%). Nearly three-quarters (72.3%) of patients would
      choose home hospital if it were available. CONCLUSION: Patients may be ready to
      accept home hospital as an alternative for acute care. The acceptability of home
      hospital to acutely ill older patients is a critical factor in the development of
      this alternative for care and has the potential for improving satisfaction with
      care, reducing complications, hastening return to function, and, possibly, of
      lowering costs of care.

PMID- 9588375
TI  - The effect of a physician assistant on the hospitalization of nursing home
      residents.
AB  - OBJECTIVES: To describe the impact of regular visits to a nursing home by a
      gerontologist physician assistant (PA) on the hospitalization and medical costs
      of patients. DESIGN: A 6-year case series (1992-1997) incorporating events before
      and after introduction of a PA in May 1994. The PA visited the nursing home 3 to
      4 times per week, provided nearly all of the acute medical care, and alternated
      routine visits with supervising physicians. SETTING: A 92-bed teaching nursing
      home in central Georgia. MEASUREMENTS: Demographics of the nursing home
      population; hospitalizations of residents, including major diagnosis and length
      of stay; number and site of all resident deaths; costs of physician and PA
      services and hospital costs. RESULTS: After the introduction of the physician
      assistant, the number of annual hospital admissions fell by 38.0%, and the total
      number of hospital days per 1000 patient years fell by 68.6% (from 4170 in 1992
      to 1310 in 1997). The number of nursing home visits increased by 62.1%. Annual
      Medicare-allowed charges for MD and PA services increased by $22,304, but this
      was more than offset by a decline in hospital DRG reimbursements of $96,043.
      CONCLUSIONS: The introduction of regular visits to nursing home patients by a
      physician assistant can reduce hospitalization and medical costs of these frail
      older people.

PMID- 9588376
TI  - Underutilization of aspirin in older patients with prior myocardial infarction at
      the time of admission to a nursing home.
AB  - OBJECTIVE: To investigate the prevalence of aspirin use in older patients with
      prior myocardial infarction at the time of admission to a nursing home. DESIGN:
      In a prospective study, the prevalence of aspirin use in 350 consecutive older
      patients with documented Q-wave myocardial infarction and no contraindications to
      aspirin use was investigated in patients aged 60 years or older at the time of
      admission to a nursing home. SETTING: A large, long-term, healthcare facility.
      PATIENTS: The patients included 231 women and 119 men, mean age 81 +/- 8 years
      (range 60 to 100). MEASUREMENTS AND MAIN RESULTS: Of the 350 patients with
      documented Q-wave myocardial infarction and no contraindications to aspirin
      therapy, 60 patients (17%) were receiving aspirin at the time of admission to the
      nursing home. CONCLUSION: There is a marked underutilization of aspirin in the
      treatment of older patients with documented prior myocardial infarction at the
      time of admission to a nursing home.

PMID- 9588377
TI  - Depression and disability associated with impaired vision: the MoVies Project.
AB  - OBJECTIVE: To assess how depression and impaired vision relate to disability in
      older people. DESIGN: An epidemiological survey of an age-stratified random
      community sample. SETTING: The rural mid-Monongahela Valley in South-western
      Pennsylvania. PARTICIPANTS: A total of 872 noninstitutionalized persons aged 68
      and older, fluent in English, and with at least a grade 6 education.
      MEASUREMENTS: Demographics, self-reported vision impairment, OARS Instrumental
      Activities of Daily Living (IADL), and modified Center for Epidemiologic Studies
      Depression scale to assess depression. RESULTS: Compared with subjects with
      intact vision, those with impaired vision were more likely to have five or more
      depressive symptoms (29.7% vs 8.5%; OR = 4.6, 95% CI = 2.2, 9.6) and to be more
      functionally impaired (OR = 9.7, 95% CI = 4.9, 19.2). The number of depressive
      symptoms (1-4: OR = 2.4, CI = 1.8, 3.4) and (5+: OR = 5.9, CI = 3.6, 9.8) was
      associated independently with IADL impairment after controlling for vision, age,
      and gender. CONCLUSIONS: Impaired vision and depression are both associated
      strongly with functional impairment in this community population of older adults.
      Depression, however, increases the odds of functional impairment independent of
      vision impairment. Treating depression may reduce excess disability associated
      with impaired vision.

PMID- 9588378
TI  - Alprazolam as an alternative to low-dose haloperidol in older, cognitively
      impaired nursing facility patients.
AB  - OBJECTIVES: To determine if alprazolam is equally as effective as low dose
      haloperidol in managing disruptive behavioral episodes associated with delirium,
      dementia, and amnesic and other cognitive disorders (formerly called organic
      mental syndromes). SETTING: Twenty-five community nursing homes in western
      Washington. PARTICIPANTS: Older nursing home residents (N = 48) receiving a low
      dose neuroleptic for the treatment of agitation and behavioral disturbances.
      INTERVENTION: Randomized, double-blind, crossover trial of alprazolam and low
      dose haloperidol. Data were gathered at baseline and at the end of 6 and 12 weeks
      from direct observation and from clinical forms completed routinely by trained
      nurses. MEASUREMENTS: Number of behavioral episodes, activities of daily living
      as measured by the Blessed Dementia Scale, extrapyramidal symptoms as measured by
      the Abnormal Involuntary Movement Scale (AIMS), and psychopathology as measured
      by the Clinical Global Impressions (CGI) and the Sandoz Clinical Assessment -
      Geriatric (SCAG) scales. RESULTS AND CONCLUSIONS: No significant differences were
      observed between patients using haloperidol or alprazolam in terms of behavioral
      episodes per week. Further, with few exceptions, no significant differences were
      found in other outcome scales. Essentially the same findings were found when
      analyses were repeated for subgroups of patients with high levels of cognitive
      impairment and for patients with low and high levels of recorded problematic
      behavioral episodes. Alprazolam was as effective as low dose haloperidol in this
      population.

PMID- 9588379
TI  - Mycobacterium tuberculosis genome sequence completed.

PMID- 9588380
TI  - The effect of HMO status on the outcomes of home-care after hospitalization in a
      Medicare population.
AB  - OBJECTIVE: The literature suggests that Medicare health maintenance organization
      (HMO) patients may have poorer outcomes with formal home-health care than do fee
      for-service (FFS) patients, but it is unclear whether this is related to case-mix
      or quality. Our objective was to compare the home-health care outcomes for HMO
      and FFS Medicare patients after hospitalization for stroke, COPD, CHF, hip
      replacement, or hip fracture with fixation or replacement while controlling for
      site of discharge and other patient characteristics. DESIGN: Patients were
      identified before hospital discharge with data collected at that time and then
      prospectively for 1 year. SETTING: Nineteen acute general hospitals in
      Minneapolis/St. Paul, Minnesota. PATIENTS: All Medicare patients in the above
      hospitals identified predischarge with stroke, COPD, CHF, hip replacement, or hip
      fracture with fixation or replacement. MEASURES:  OUTCOME: weighted ADL scale and
      hospital readmission. Independent factors: site of discharge, HMO status,
      comorbidity, severity, and demographic factors. RESULTS: A total of 970 subjects
      were studied, 211 of whom were discharged to home-care. HMO patients were more
      likely to be discharged to a nursing home than to home-care after controlling for
      other factors (OR = 1.7; P = .015). After controlling for site of discharge and
      patient characteristics through either propensity scores or regression analysis,
      there was no statistically significant difference in ADL function at 6 weeks or
      at 6 months between HMO and FFS patients. Nor was there was a statistically
      significant difference in hospital readmission rates at 6 weeks and 6 months
      between HMO and FFS home-care patients. CONCLUSIONS: The outcomes of Medicare HMO
      patients discharged to home-care are not worse than those of FFS patients.

PMID- 9588381
TI  - The management of chronic pain in older persons: AGS Panel on Chronic Pain in
      Older Persons. American Geriatrics Society.

PMID- 9588382
TI  - The search to improve safe vehicular operation among older drivers: are we
      reaching our destination?

PMID- 9588383
TI  - Pressure ulcer products and devices: are they safe, much less effective?

PMID- 9588384
TI  - Aging: a global theme issue.

PMID- 9588386
TI  - Brain SPECT scanning.

PMID- 9588385
TI  - Severe gastrointestinal dysfunction and retention of extended release nifedipine
      tablets.

PMID- 9588387
TI  - Screening for "cognitive impairment, no dementia" in older adults.

PMID- 9588388
TI  - Ethical concerns about research on incompetent persons.

PMID- 9588389
TI  - Oral inhibitors of platelet membrane receptor glycoprotein IIb/IIIa in clinical
      cardiology: issues and opportunities.
AB  - The feedback amplification loop in the progress of medicine, from basic findings
      and clinical observations to hypothesis generation and new research, is presently
      particularly dynamic in acute coronary syndromes. As the role of thrombosis
      formation in etiopathology of these syndromes has emerged, antithrombotic therapy
      has become standard practice. Numerous trials with antiplatelet drugs and meta
      analyses of these trials have established the efficacy of aspirin, launching new
      research in platelet physiology, understanding of pathophysiology, and therapy.
      Recognition of the role of glycoprotein IIb/IIIa receptor in health and disease
      and of its dynamic and ligands lead to production of a monoclonal antibody
      against the receptor, which has become the first anti-integrin therapy approved
      for clinical use. Synthetic compounds were subsequently produced containing the
      specific arginine-glycine-aspartic acid (RGD) sequence for fibrinogen binding to
      the receptor. Inhibitors are now available for oral use, allowing prolonged
      blockade of the receptor and opportunities for new research and hypothesis
      generation as well as better patient care. This supplement to the American Heart
      Journal summarizes a workshop whose goal was to generate a discussion among
      fundamentalists and clinicians on methods for monitoring platelet function with
      these drugs and investigation of consequences of chronic receptor occupancy.

PMID- 9588390
TI  - Long-term administration of glycoprotein IIb/IIIa antagonists.

PMID- 9588391
TI  - Platelet aggregation in flow: differential roles for adhesive receptors and
      ligands.
AB  - This article addresses the flow-dependent differential roles of the platelet
      receptors, glycoprotein (GP) GPIb and GPIIb-IIIa, in platelet aggregation
      mediated by ristocetin and soluble von Willebrand factor (vWF), by adenosine
      diphosphate (ADP) and soluble fibrinogen (Fg), and by thrombin and ADP in absence
      of exogenous ligands. Platelet-rich plasma or "activated" washed platelets were
      sheared in a coaxial cylinder at 100 to 1000 sec(-1) or in tubular flow, with
      surface ligands monitored by flow cytometry, with fluorescently labeled soluble
      ligands or monoclonal antibodies against specific adhesive domains on receptors
      or ligands. Aggregation was quantitated by monitoring the change in particle
      concentration with time by particle counting, and expressed as Capture
      efficiencies (CE) = Experimental/calculated initial rates of aggregation. The
      contributions of adhesive domains on putative ligands or receptors mediating
      aggregation at any given flow condition were evaluated with monoclonal antibodies
      or peptides known to block these adhesive sites. Surprisingly, ristocetin, which
      "chemically activates" GPIb/vWF to mediate spontaneous binding of the ligand to
      its receptor, at low concentrations yielding <2000 platelet-bound vWF monomers,
      gave efficient aggregation even at 1000 sec(-1) (CE = 0.34 +/- 0.02, n = 11) with
      only GPIb required. The physiologic activators ADP and thrombin both supported
      efficient aggregation of washed platelets with no exogenous ligands at 1000 sec(
      1) by surface-secreted vWF (CE = 0.08 +/- 0.01, n = 6), in contrast to poorer ADP
      and soluble Fg-mediated aggregation in the absence of secretion (CE = 0.05). The
      secreted, platelet-bound, vWF-mediated aggregation completely depends on GPIIb
      IIIa but partially and increasingly requires GPIb with increasing shear.
      Molecular models for these interactions are presented in terms of "rolling" and
      "firm" capture. Flow conditions will be critically important in designing and
      selecting anti-thrombotic drugs directed against the appropriate adhesive domains
      on receptors and ligands, which likely include other members such as
      thrombospondin and P-selectin.

PMID- 9588392
TI  - Blood flow and antithrombotic drug effects.
AB  - This paper reviews the importance of blood flow phenomena in models of
      experimental thrombosis used for measuring antithrombotic drug efficacy. The
      characteristics of these systems and their application for studies with human
      blood and in animal models are considered. Central to these investigations has
      been the development of various types of perfusion chambers in which a
      thrombogenic test surface is exposed to flowing blood under well-defined
      conditions of blood flow and device geometry. Such perfusion chambers, which have
      been used in vitro, ex vivo, and in vivo by insertion into arteriovenous shunts
      in various animal species, have allowed reproducible testing of both conventional
      and experimental agents. Shear-dependent antithrombotic effects have been
      observed with anticoagulants such as heparin and with selective inhibitors of
      thrombin, factor Xa, and factor VIIa. However, the degree of shear dependency
      depends on the chemical composition of the thrombogenic surface; for example,
      anticoagulant effects may be more pronounced on a tissue factor-rich surface than
      on a collagen-rich surface, particularly at venous or low arterial shear rates.
      Platelet inhibitors such as aspirin, thromboxane antagonists, or inhibitors of
      von Willebrand factor platelet interactions are also shear dependent, being more
      efficient at high shear rates. In contrast, inhibitors of adenosine diphosphate
      dependent platelet reactions or antagonists of the platelet membrane glycoprotein
      IIb/IIIa complex are shear rate independent. At very high shear rates
      characteristic of severely stenotic arteries, aspirin loses its direct
      antithrombotic effect, whereas adenosine diphosphate pathway inhibitors and GP
      IIb/IIIa antagonists are still beneficial. In general, results obtained with many
      of these models have predicted antithrombotic efficacy in human beings when
      comparisons were possible. Therefore shear-dependent models of experimental
      thrombosis are routinely used in the evaluation of antithrombotic pharmacologic
      agents, both preclinically and clinically.

PMID- 9588393
TI  - Platelet-leukocyte interactions.
AB  - Platelet-leukocyte interactions may contribute to the development of several
      pathological conditions, including myocardial ischemic disorders. Using an in
      vitro system that simulates vascular flow conditions, we investigated platelet
      neutrophil adhesion. Collagen-adherent platelets were shown to express P-selectin
      and were able to mediate the binding of flowing neutrophils. Some of the adherent
      neutrophils displayed signs of cellular activation. Flow cytometric analyses
      revealed that activation induced a rapid and marked reduction of the P-selectin
      ligand, with levels decreased by 71% after 15 minutes of stimulation. Using a
      visual assay of platelet-neutrophil rosetting, we showed that the P-selectin
      ligand was translocated and clustered at the uropod of neutrophils after the
      shape changes and polarization induced by stimulation. Activated neutrophils that
      were bound to surface-adherent platelets also displayed the clustering of P
      selectin ligand at the uropod, and these neutrophils detached from the platelets
      when a shear stress was applied through the adhesion chamber. These results
      indicate that stimulation of neutrophils induces changes in the surface
      expression and distribution of the ligand for P-selectin, and that these changes
      might influence the adhesive interactions occurring between neutrophils and
      activated platelets.

PMID- 9588394
TI  - Glycoprotein IIb/IIIa antagonists: potential induction and detection of drug
      dependent antiplatelet antibodies.
AB  - Development of acute, severe thrombocytopenia has been reported in several
      patients treated with a chimeric monoclonal antibody fragment to the platelet
      glycoprotein IIb/IIIa (GPIIb/IIIa) complex. However, the propensity of oral
      GPIIb/IIIa antagonists to induce antibody-mediated thrombocytopenia or platelet
      dysfunction with chronic exposure is unknown. There is evidence to suggest that a
      small percentage of otherwise healthy individuals have preexisting serum
      antibodies to conformation-dependent epitopes in the GPIIb/IIIa complex that are
      induced by certain members of this class of compounds that function as mixed
      agonists/antagonists. Additional studies are needed to identify the epitopes
      recognized by these antibodies and the requirement for the drug or a drug
      metabolite to be present for antibody binding and detection. Detailed immunologic
      studies of antibodies from patients in whom immune thrombocytopenia develops
      after receiving oral GPIIb/IIIa antagonists may also provide insight into the
      mechanism by which activated platelets are normally cleared from the circulation.

PMID- 9588395
TI  - Methods for monitoring platelet function.

PMID- 9588396
TI  - Assessment of platelet function assays.
AB  - Optical aggregometry, traditionally used to assess platelet function, is highly
      dependent on sample preparation and technical procedure; as a result, data from
      various laboratories can be quite variable. In a study designed to assess the
      sources of variation, it was determined that the total standard deviation ranged
      from 3.6% to 7.7%. The assay variation by one analyst on one aggregometer on a
      single day ranged from 1.7 to 4.6. Day-to-day variation contributed 42% to 63% of
      the total variation, between-operator variation contributed 1% to 33% of the
      total variation, and within [between repeat measurements for a given sample by a
      given operator on a single day] variation contributed 22% to 36% of the total
      variation. Because of the disadvantages associated with optical aggregometry,
      alternate platelet function assays were considered and their correspondence to
      optical aggregometry was evaluated: activated clotting time, whole blood
      aggregometry, platelet count ratio, Platelet Function Analyzer (PFA-100, Dade),
      and Rapid Platelet function Assay (Accumetrics). Of those assays evaluated,
      activated clotting time and PFA-100 are assays that measure aspects of
      coagulation and hemostasis, whereas whole blood aggregometry, platelet count
      ratio, and RPFA are more closely related to platelet function. Each assay has
      value in monitoring various aspects of the coagulation process. The best method
      for monitoring safety and efficacy of various inhibitors of platelet function
      will ultimately be determined by clinical trials.

PMID- 9588397
TI  - Expression of ligand-induced binding sites on glycoprotein IIb/IIIa complexes and
      the effect of various inhibitors.
AB  - Glycoprotein (GP) IIb/IIIa is a therapeutic target for the blockade of platelet
      aggregation during acute coronary syndromes. Peptides, peptidomimetics, and
      antibodies are generated that competitively block the binding of fibrinogen or
      von Willebrand factor to the activated GPIIb/IIIa complex. Binding of these
      receptor blockades to GPIIb/IIIa effectively inhibits the formation of the
      platelet aggregate because ligand binding to the activated GPIIb/IIIa is the
      final common pathway to thrombus formation. In addition, bound antagonists induce
      a conformational change in the receptor. This conformational change, also called
      a ligand-induced binding site, can be used as a marker for receptor occupancy by
      GPIIb/IIIa receptor blockades. Using the binding properties of the D3 monoclonal
      antibody that binds with high affinity to the antagonist bound GPIIb/IIIa, we
      have developed a new method for monitoring the extent of receptor blockade by
      GPIIb/IIIa antagonists. This method has specific advantages over the interpatient
      variability of the aggregation assay and provides a method for the evaluation of
      appropriate target levels of GPIIb/IIIa blockade.

PMID- 9588398
TI  - Novel methods for assessing platelet function.

PMID- 9588399
TI  - Cone and plate(let) analyzer: monitoring glycoprotein IIb/IIIa antagonists and
      von Willebrand disease replacement therapy by testing platelet deposition under
      flow conditions.
AB  - Exposure of citrated whole blood samples to polystyrene plates under flow
      conditions with the cone and plate(let) analyzer (CPA) results in surface
      immobilization of plasma von Willebrand factor (vWF) followed by platelet
      deposition. Staining the plates allows measurement of the percentage of surface
      covered (SC) by the adhered particles and their average size (AS). Both SC and AS
      parameters depend on platelet count and hematocrit level and reach maximal values
      after 2 minutes; only AS is shear rate dependent. Under optimal assay conditions
      (2 minutes at 1800 sec(-1)) normal blood samples yielded an SC of 14.9% +/- 2.5%
      and an AS of 39.4 +/- 5.2 microm2. Severe von Willebrand disease (eight patients)
      yielded low SC (5.2% +/- 2.1%), which was restored to normal by testing with vWF
      precoated surfaces. Glanzmann's thrombasthenia (six patients) samples
      demonstrated no adhesion of platelet at all. Blocking of the glycoprotein (GP)
      IIb/IIIa receptor by the chimeric antibody abciximab, and of the GPIb by a
      recombinant vWF fragment, have yielded a dose-response inhibition demonstrating
      the crucial role of these receptors in platelet deposition on polystyrene plates
      in this system. Evaluation of a patient with severe von Willebrand disease
      receiving replacement vWF factor VIII therapy revealed a comparable response as
      tested by both the CPA and the Ricof methods. In vitro testing of the GPIIb/IIIa
      blocking by a nonpeptidic analogue tirofiban and abciximab revealed a good
      correlation between the CPA test and the routine aggregometry. Eleven patients
      treated by abciximab after coronary angioplasty were studied by the CPA during
      the first 24 hours, demonstrating a marked decrease in SC and AS, with some
      diversity in the responses. We conclude that the CPA test is suitable for
      evaluation of primary hemostasis and for monitoring of anti-platelet drugs.

PMID- 9588400
TI  - New antiplatelet agents for acute coronary syndromes.

PMID- 9588401
TI  - Simple electrocardiographic markers for the prediction of paroxysmal idiopathic
      atrial fibrillation.
AB  - BACKGROUND: The prolongation of intraatrial and interatrial conduction time and
      the inhomogeneous propagation of sinus impulses are well known electrophysiologic
      characteristics in patients with paroxysmal atrial fibrillation (PAF). METHODS:
      To search for possible electrocardiographic markers that could serve as
      predictors of idiopathic PAF, we measured the maximum P-wave duration (P maximum)
      and the difference between the maximum and the minimum P-wave duration (P
      dispersion) from the 12-lead surface electrocardiogram of 60 patients with a
      history of idiopathic PAF and 40 age-matched healthy control subjects. RESULTS: P
      maximum and P dispersion were found to be significantly higher in patients with
      idiopathic PAF than in control subjects. A P maximum value of 110 msec and a P
      dispersion value of 40 msec separated patients from control subjects, with a
      sensitivity of 88% and 83% and a specificity of 75% and 85%, respectively.
      CONCLUSIONS: P maximum and P dispersion are simple electrocardiographic markers
      that could be used for the prediction of idiopathic PAF.

PMID- 9588402
TI  - A randomized, double-blind comparison of intravenous diltiazem and digoxin for
      atrial fibrillation after coronary artery bypass surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) after coronary bypass graft surgery may
      result in hypotension, heart failure symptoms, embolic complications, and
      prolongation in length of hospital stay (LOHS). The purpose of this study was to
      determine whether intravenous diltiazem is more effective than digoxin for
      ventricular rate control in AF after coronary artery bypass graft surgery. A
      secondary end point was to determine whether ventricular rate control with
      diltiazem reduces postoperative LOHS compared with digoxin. METHODS AND RESULTS:
      Patients with AF and ventricular rate > 100 beats/min within 7 days after
      coronary artery bypass graft surgery were randomly assigned to receive
      intravenous therapy with diltiazem (n = 20) or digoxin (n = 20). Efficacy was
      measured with ambulatory electrocardiography (Holter monitoring). Safety was
      assessed by clinical monitoring and electrocardiographic recording. LOHS was
      measured from the day of surgery. Data were analyzed with the intention-to-treat
      principle in all randomly assigned patients. In addition, a separate intention-to
      treat analysis was performed excluding patients who spontaneously converted to
      sinus rhythm. In the analysis of all randomly assigned patients, those who
      received diltiazem achieved ventricular rate control (> or = 20% decrease in
      pretreatment ventricular rate) in a mean of 10 +/- 20 (median 2) minutes compared
      with 352 +/- 312 (median 228) minutes for patients who received digoxin (p <
      0.0001). At 2 hours, the proportion of patients who achieved rate control was
      significantly higher in patients treated with diltiazem (75% vs 35%, p = 0.03).
      Similarly, at 6 hours, the response rate associated with diltiazem was higher
      than that in the digoxin group (85% vs 45%, p = 0.02). However, response rates
      associated with diltiazem and digoxin at 12 and 24 hours were not significantly
      different. At 24 hours, conversion to sinus rhythm had occurred in 11 of 20 (55%)
      patients receiving diltiazem and 13 of 20 (65%) patients receiving digoxin (p =
      0.75). Results of the analysis of only those patients who remained in AF were
      similar to those presented above. There was no difference between the diltiazem
      treated and digoxin-treated groups in postoperative LOHS (8.6 +/- 2.2 vs 7.7 +/-
      2.0 days, respectively, p = 0.43). CONCLUSIONS: Ventricular rate control occurs
      more rapidly with intravenous diltiazem than digoxin in AF after coronary artery
      bypass graft surgery. However, 12- and 24-hour response rates and duration of
      postoperative hospital stay associated with the two drugs are similar.

PMID- 9588403
TI  - Increased atrial vulnerability in arrhythmogenic right ventricular disease.
AB  - Supraventricular tachyarrhythmias (SVTA) may occur in patients with the
      arrhythmogenic right ventricular dysplasia (ARVD). The purpose of the study was
      to evaluate the incidence of SVTA in 47 patients with ARVD proved by right
      ventricular angiography. Thirty-three men and 14 women, aged 21 to 72 years (mean
      44 +/- 18) were admitted for nonsustained or sustained ventricular tachycardia.
      Eight patients had a history of spontaneous SVTA several years before ventricular
      tachycardia occurrence. Protocol of the study consisted of programmed atrial
      stimulation with one and two extrastimuli delivered during sinus rhythm and two
      driven rhythms (600 and 400 msec), programmed ventricular stimulation with up to
      three extrastimuli and was performed in the control state and after infusion of
      isoproterenol. The results of programmed atrial stimulation were compared with
      those obtained in 36 asymptomatic subjects without heart disease and with a mean
      age of 50 +/- 18 years (control group). Sustained SVTA (> 1 minute) was induced
      in seven of eight patients with spontaneous SVTA, in 27 (69%) of those with ARVD,
      who did not have spontaneous SVTA, and in two control subjects (5.5%) (p <
      0.001). SVTA was inducible in the control state, but ventricular tachycardia
      induction required isoproterenol in 11 of 27 patients. Two patients without SVTA
      history but with inducible SVTA developed later spontaneous SVTA. ARVD was
      associated with a significantly higher incidence of inducible SVTA than in a
      control population. Supraventricular tachycardias may precede ventricular
      tachycardias. This association argues for a diffuse myocardial disorder in ARVD.

PMID- 9588404
TI  - Time-dependent changes of heart rate variability after percutaneous transluminal
      angioplasty.
AB  - OBJECTIVES: It is not known whether the improvement of myocardial perfusion by
      percutaneous transluminal coronary angioplasty (PTCA) is followed by a response
      of the autonomic nervous system depending on the recovery of the myocardium. In
      this study we investigated changes of heart rate variability parameters in
      patients before and after PTCA at different time intervals. METHODS: In 42
      patients with coronary artery disease documented on angiography, before and after
      PTCA 24-hour measurements of heart rate variability (HRV) were performed from
      Holter tapes. The time elapsed between the two measurements was 3 to 4 days in 26
      patients and 6 to 8 months in 16 patients. Time domain parameters of HRV were
      calculated. RESULTS: Comparison of the two recordings showed that the parameters
      rMSSD, pNN50, and SDNN index decreased, whereas SDNN and SDANN increased. These
      changes were not statistically significant. A subgroup analysis revealed
      different results for patients with and without previous myocardial infarction:
      the parasympathetically and more sympathetically influenced parameters revealed
      different changes in these groups. Other variables such as ejection fraction or
      severity of coronary artery disease did not influence the HRV results. Although
      no statistically significant difference was seen on comparison of the patients
      with different recording intervals, patients with a longer interval between the
      two measurement periods showed higher values of all HRV parameters closer to
      normalized values. This observation may be explained by a delayed recovery of
      myocardial function after successful revascularization by PTCA.

PMID- 9588405
TI  - Alterations of autonomic nervous activity preceding nocturnal variant angina:
      sympathetic augmentation with parasympathetic impairment.
AB  - BACKGROUND: Autonomic nervous discharge has been implicated in the pathogenesis
      of coronary artery spasm. METHODS: Cardiac autonomic nervous activities were
      evaluated from the power of the low-frequency and the high-frequency spectral
      components of heart rate variability with Holter monitoring in 18 patients with
      nocturnal variant angina. Samples during the first 512 seconds of each 10-minute
      period from 60 minutes before to immediately before an anginal attack occurring
      during the night or at dawn (2:00 to 7:00 AM) were analyzed by fast Fourier
      transformation. RESULTS: The R-R interval during the 10- to 0-minute period was
      significantly shorter than those during the other 10-minute periods. The
      coefficient of variance of the high-frequency component (0.15 to 0.40 Hz) (CVHF)
      from the 10- to 0-minute period was not significantly different from the other 10
      minute periods. However, both the coefficient of variance of the low-frequency
      component (0.04 to 0.15 Hz) (CVLF) and the ratio of CVLF and CVHF (CVLF/CVHF)
      were significantly greater during the 10- to 0-minute period than those during
      the 30- to 20-minute period, respectively. A significant nighttime fluctuation in
      the spectral components of heart rate variability with a peak in the CVHF and a
      nadir in both the CVLF and CVLF/CVHF observed in the control group was blunted in
      the patients during the attack-free periods while they were medicated with
      calcium entry blockers. CONCLUSION: Sympathovagal imbalance, sympathetic
      activation without parasympathetic augmentation, enhanced in the early morning
      may play an important role in the genesis of coronary artery spasm in patients
      with nocturnal variant angina.

PMID- 9588406
TI  - Pathologic anatomy of corrected transposition of the great arteries: medical and
      surgical implications.
AB  - BACKGROUND: Because the double-switch operation (atrial switch plus arterial
      switch) has recently become feasible in selected patients with congenitally
      physiologically corrected transposition of the great arteries, a detailed
      understanding of the pathologic anatomy is now mandatory for cardiologists,
      radiologists, and surgeons. METHODS: A detailed study of the pathologic anatomy,
      the clinical implications, and the surgical implications was undertaken on 33
      postmortem cases with two ventricles. A companion study was also performed of 44
      postmortem cases with functionally only one ventricle. Hence this was an
      investigation of 77 postmortem cases. RESULTS: Three main anatomic types of
      corrected transposition of the great arteries (TGA) with two ventricles were
      found: (1) TGA with solitus atria (S), L-loop ventricles (L), and L-TGA (L), that
      is, TGA [S,L,L] in 31 cases (94%); (2) TGA with solitus atria (S), L-loop
      ventricles (L), and D-TGA (D), that is, TGA [S,L,D] in 1 case (3%); and (3) TGA
      with inverted atria (I), D-loop ventricles (D), and D-TGA (D), that is, TGA
      [I,D,D] in 1 case (3%). Associated malformations resulted in 13 anatomic
      subtypes. In classical corrected TGA [S,L,L] with two ventricles, anomalies of
      the left-sided systemic tricuspid valve were present in 97%, with malformations
      of the left-sided systemic right ventricle in 91%. CONCLUSIONS: The findings in
      corrected TGA with two ventricles and in cases with single ventricle support the
      view that anatomic repair such as the double-switch procedure, or left-sided
      right ventricle bypass such as the modified Norwood procedure followed by the
      modified Fontan procedure, is indicated in selected patients.

PMID- 9588408
TI  - Randomized, controlled trial of RheothRx (poloxamer 188) in patients with
      suspected acute myocardial infarction. RheothRx in Myocardial Infarction Study
      Group.
AB  - BACKGROUND: Patients with acute myocardial infarction (AMI) who are not eligible
      for thrombolytic therapy or primary coronary angioplasty are distinguished by
      advanced age, complicated medical histories, relatively frequent use of prior
      revascularization procedures, and worse outcomes than their counterparts who are
      eligible for reperfusion therapy. METHODS AND RESULTS: The purpose of this
      randomized, controlled trial was to determine whether RheothRx, a hemorheologic
      agent, reduced myocardial infarct size and improved left ventricular function in
      patients who had suspected AMI at the time of hospital admission and were not
      eligible for reperfusion therapy. Patients were randomly assigned to RheothRx (n
      = 97) or placebo (n = 99). Patients in the two groups were similar with respect
      to age, sex, medical history, and clinical presentation. Enzyme evidence of AMI
      was present in 69% of the treatment group and 70% of the placebo group. Infarct
      size measured before hospital discharge was similar in the two groups (14.1% +/-
      18.5% vs 11.7% +/- 14.1%, p = 0.60), although left ventricular ejection fraction
      was lower in the treatment group (47 +/- 14 vs 52 +/- 11, p = 0.026). Hospital
      mortality rate was 11.3% and 7.1% in patients receiving RheothRx and patients
      receiving placebo, respectively (p = 0.30). There was a higher occurrence of
      acute renal dysfunction in the RheothRx group (12% vs 2%, p = 0.005). Because of
      changes in drug dosage necessitated by the occurrence of acute renal dysfunction,
      the trial was stopped. CONCLUSIONS: In this study of patients who had suspected
      AMI and were not eligible for thrombolytic therapy, RheothRx did not decrease
      infarct size or favorably alter outcome. The need for effective treatment for
      this large patient population remains largely unmet.

PMID- 9588407
TI  - Early assessment and in-hospital management of patients with acute myocardial
      infarction at increased risk for adverse outcomes: a nationwide perspective of
      current clinical practice. The National Registry of Myocardial Infarction (NRMI
      2) Participants.
AB  - BACKGROUND: Therapeutic decision making in critically ill patients requires both
      prompt and comprehensive analysis of available information. Data derived from
      randomized clinical trials provide a powerful tool for risk assessment in the
      setting of acute myocardial infarction (MI); however, timely and appropriate use
      of existing therapies and resources are the key determinants of outcome among
      high-risk patients. METHODS: Demographic, procedural, and outcome data from
      patients with MI were collected at 1073 U.S. hospitals collaborating in the
      National Registry of MI (NRMI 2). Patients were classified on hospital arrival as
      either "low risk" or "high risk" according to a modified Thrombolysis in
      Myocardial Infarction II Risk Scale based on predetermined demographic,
      electrocardiographic, and clinical features. RESULTS: Among the 170,143 patients
      enrolled, 115,222 (67.5%) were classified as low risk and 55,521 (32.5%) as high
      risk for in-hospital death, recurrent ischemia, recurrent MI, congestive heart
      failure, and stroke. Using a composite unsatisfactory outcome measure, in
      hospital adverse events were had by a greater proportion of patients initially
      classified as high risk compared with those classified as low risk. By
      multivariate analysis, age >70 years, prior MI, Killip class >1, anterior site of
      infarction, and the combination of hypotension and tachycardia were independent
      predictions of poor outcome in patients with or without ST-segment elevation on
      the presenting electrocardiogram. High-risk patients with ST-segment elevation
      were treated with thrombolytics (47.5%) or alternative forms of reperfusion
      therapy (9.3%) within 62 minutes and 226 minutes of hospital arrival,
      respectively. High-risk patients offered reperfusion therapy were also more
      likely to receive aspirin, beta-blockers (intravenous, oral) and angiotensin
      converting enzyme inhibitors within 24 hours of infarction (all p < 0.0001),
      survive their event (8.4% versus 21.4% p < 0.0001), and leave the hospital sooner
      than those not reperfused. CONCLUSIONS: This large registry experience included
      more than 150,000 nonselected patients with MI and suggests that high-risk
      patients can be identified on initial hospital presentation. The current use of
      reperfusion and adjunctive therapies among high-risk patients is suboptimal and
      may directly influence outcome. Randomized trials designed to test the impact of
      specific management strategies on outcome according to initial risk
      classification are warranted.

PMID- 9588409
TI  - Admission clinical and electrocardiographic characteristics predicting an
      increased risk for early reinfarction after thrombolytic therapy.
AB  - BACKGROUND: This study assessed the ability of clinical and electrocardiographic
      variables routinely obtained on admission to identify patients with acute
      myocardial infarction treated with thrombolytic therapy at risk of early
      reinfarction. METHODS AND RESULTS: The study included 2602 patients who received
      thrombolytic therapy for acute myocardial infarction. Baseline demographic
      variables and admission clinical and electrocardiographic variables were compared
      between patients with and without reinfarction. Multivariable logistic regression
      technique was used and included recurrent infarction as the dependent variable,
      and baseline demographic, clinical, and electrocardiographic variables as
      independent variables. History of hypertension (odds ratio [OR] 1.52, 95%
      confidence interval [CI] 1.00 to 2.31) and diabetes mellitus (OR 1.59, 95% CI
      1.00 to 2.53) were associated with a higher risk, and current smoking was
      associated with a lower risk (OR [no versus yes] 1.64, 95% CI 1.05 to 2.58) of
      early hospital reinfarction. Distortion of the terminal portion of the QRS
      complex (OR 1.86, 95% CI 1.20 to 2.87) and absence of abnormal Q waves on
      admission (OR 1.54, 95% CI 0.98 to 2.43) were associated with increased risk of
      early reinfarction. CONCLUSIONS: A simple electrocardiographic sign is a reliable
      predictor of early reinfarction among patients who receive thrombolytic therapy
      for acute myocardial infarction.

PMID- 9588410
TI  - Extent of ischemic stimulus and plasma beta-endorphin levels in silent myocardial
      ischemia.
AB  - BACKGROUND: Beta-endorphin has been reported to play a role in the mechanism of
      silent myocardial ischemia. OBJECTIVES: Plasma beta-endorphin levels during
      coronary angioplasty-induced silent and symptomatic myocardial ischemia were
      compared with those during exercise-induced silent ischemia. METHODS AND RESULTS:
      The study population consisted of 40 nondiabetic patients with angioplasty
      indicated coronary artery disease. All patients underwent exercise treadmill
      testing 2 to 4 days before angioplasty. Patients were divided into three groups:
      group 1, 10 patients with silent ischemia during exercise and angioplasty; group
      2, 15 patients with silent ischemia during exercise and symptomatic ischemia
      during angioplasty; and group 3, 15 patients with symptomatic ischemia during
      both exercise and angioplasty. In group 1, plasma beta-endorphin levels during
      balloon inflation were significantly higher than in groups 2 and 3 and also
      significantly higher than during exercise. In group 2, plasma beta-endorphin
      levels were significantly elevated at exercise-induced silent myocardial ischemia
      and balloon-induced symptomatic myocardial ischemia, but the levels between
      exercise and balloon inflation were not significantly different. CONCLUSIONS: For
      "silent" myocardial ischemia, it may be necessary for beta-endorphin levels to
      increase to sufficiently high levels to suppress anginal symptoms in response to
      the degree of ischemic stimuli.

PMID- 9588411
TI  - Comparison of Quality of Well-Being scale and NYHA functional status
      classification in patients with atrial fibrillation. New York Heart Association.
AB  - BACKGROUND: There is an increased need to provide appropriate outcomes
      evaluations. Although designed as a clinical assessment tool, the New York Heart
      Association (NYHA) classification is often used as an outcome measure. In this
      study the performance of the NYHA classification is compared with that of the
      Quality of Well-being scale (QWB), a standard outcome instrument. METHODS:
      Subjects from a clinical trial were administered both the NYHA classification and
      the QWB. Scores for patients with NYHA classification I, II, and III were
      compared by use of an ordinal regression model. RESULTS: There were significant
      differences in mean QWB score by NYHA classification (p < 0.0001). However, each
      NYHA classification score was associated with a wide range of QWB scores,
      limiting the potential usefulness of the NYHA classification as an outcome
      measure. CONCLUSIONS: The NYHA classification is not a sensitive measure of
      health-related quality of life, and its use as an outcome measure, although
      providing some insights, may result in misleading findings. The NYHA
      classification should not be used as the sole outcome measure.

PMID- 9588412
TI  - Plasma brain natriuretic peptide as a biochemical marker of high left ventricular
      end-diastolic pressure in patients with symptomatic left ventricular dysfunction.
AB  - BACKGROUND: Plasma atrial natriuretic peptide (ANP), mainly from the atrium,
      brain natriuretic peptide (BNP), mainly from the ventricle, norepinephrine (NE),
      and endothelin-1 (ET-1) levels are increased with the severity of congestive
      heart failure (CHF). Although a close correlation between the left ventricular
      end-diastolic pressure (LVEDP) and plasma ANP in patients with left ventricular
      dysfunction has been reported, it is not yet known which cardiac natriuretic
      peptide is a better predictor of high LVEDP in patients with CHF. METHODS: To
      investigate the biochemical predictors of the high LVEDP in patients with left
      ventricular dysfunction, we measured plasma ANP, BNP, NE, and ET-1 levels and the
      hemodynamic parameters in 72 patients with symptomatic left ventricular
      dysfunction. Stepwise multivariate regression analyses were also used to
      determine whether the plasma levels of ANP, BNP, NE, and ET-1 could predict high
      LVEDP. RESULTS: Although significant positive correlations were found among the
      plasma levels of ANP, BNP, ET-1, and NE and the LVEDP, only BNP (p = 0.0001) was
      an independent and significant predictor of high LVEDP in patients with CHF. In
      all eight patients with severe CHF measured for hemodynamics before and after the
      treatments, the plasma BNP levels decreased in association with the decrease of
      LVEDP, whereas other factors increased in some patients despite the decrease of
      LVEDP. CONCLUSIONS: These findings suggest that plasma BNP is superior to ANP as
      a predictor of high LVEDP in patients with symptomatic left ventricular
      dysfunction.

PMID- 9588413
TI  - Alcohol consumption and idiopathic dilated cardiomyopathy: a case control study.
AB  - BACKGROUND: Alcohol has been implicated as a risk factor for idiopathic dilated
      cardiomyopathy (DCM), but a causal relation has not been established. The
      objective of this study was to determine the association between alcohol
      consumption and DCM. METHODS: Questionnaires detailing average weekly intake of
      alcohol, total lifetime consumption, and alcohol abuse were administered in a
      cohort of well-defined patients with DCM and a randomly selected, population
      based control group. RESULTS: Significantly more of the 100 patients with DCM
      than the 211 members of the control group drank greater than the recommended
      weekly intake of alcohol (40% vs 24%; p < 0.01) and were alcohol abusers
      according to the CAGE questionnaire (27% vs 16%; p < 0.05). The average total
      lifetime consumption measured in units of alcohol was also significantly greater
      in cases than in the control group (31,200 vs 7,904; p < 0.01). Patients with
      familial DCM were not significantly more likely to consume alcohol above
      recommended limits or to be alcohol abusers compared with nonfamilial cases.
      CONCLUSIONS: This study confirms previous suspicion of a causal association
      between alcohol and DCM, with significantly more patients than members of the
      control group either abusing alcohol or drinking it in excess of recommended
      limits.

PMID- 9588414
TI  - Serotonin and heart rate in hypertensive and normotensive subjects.
AB  - Plasma and platelet levels of 5-hydroxytryptamine (5 HT) may be altered in
      essential hypertension. To establish the determinants and correlates of 5 HT in
      plasma and platelets, we studied 53 untreated subjects with essential
      hypertension (26 men; 30 whites; mean supine blood pressure 172/101 mm Hg; mean
      age 49.3 +/- 1.5 years) and 61 normotensive subjects (37 men; 47 whites; mean
      supine blood pressure 128/78 mm Hg; mean age 42.8 +/- 1.6 years). Plasma and
      platelet 5 HT were assayed by reverse-phase high performance liquid
      chromatography with electrochemical detection. No significant difference was
      found in platelet-poor plasma or platelet 5 HT levels in hypertensive or
      normotensive subjects (plasma: 43.0 +/- 4.2 and 39.6 +/- 4.4 nmol/L; platelet:
      1.65 +/- 1.22 and 1.70 +/- 1.39 nmol/10(9) cells in hypertensive and normotensive
      subjects, respectively). No significant correlation was found between plasma or
      platelet 5 HT and systolic or diastolic blood pressure (plasma: r = 0.01 and 0.01
      in normotensive subjects and r = 0.01 and -0.14 in hypertensive subjects;
      platelet: r = 0.12 and 0.13 in normotensive subjects and r = 0.02 and -0.09 in
      hypertensive subjects). However, plasma 5 HT was associated with supine and
      standing pulse rates (supine: r = 0.27, p = 0.05 in normotensive subjects and r =
      0.54, p < 0.001 in hypertensive subjects; standing: r = 0.19 and r = 0.46, p <
      0.001, respectively). Significant relations were also found between platelet 5 HT
      levels and supine and standing heart rate in the subjects mentioned above
      (supine: r = 0.28, p = 0.05 in normotensive subjects and r = 0.64, p < 0.001 in
      hypertensive subjects; standing: r = 0.24 and r = 0.51, p < 0.001, respectively).
      These associations were stronger in the hypertensive group as a whole, and they
      held when adjustment was made for differences in age and total blood cholesterol.
      The present study showed that plasma and platelet 5 HT are not significantly
      altered in hypertensive subjects. However, plasma and platelet 5 HT levels showed
      a significant association with supine and standing pulse rate predominantly in
      hypertensive subjects. This is consistent with experimental evidence of a
      positive chronotropic effect of 5 HT on perfused hearts and it suggests a
      possible role of plasma serotonin in the regulation of heart rate.

PMID- 9588415
TI  - Effects of the 14F hemopump on coronary hemodynamics in patients undergoing high
      risk coronary angioplasty.
AB  - BACKGROUND: The influence of the 14F Hemopump on coronary hemodynamics in
      patients with coronary artery disease remains unknown. METHODS: Systemic and
      coronary hemodynamic measurements were obtained in eight patients among 13 who
      underwent high-risk coronary angioplasty in our institution with the support of
      the Hemopump. Coronary blood flow velocity was measured with a 0.014-inch Doppler
      tipped guide wire both proximal and distal to the target lesion. RESULTS:
      Angioplasty decreases the diameter coronary stenosis from 76% +/- 21% to 22% +/-
      11%. Hemopump support did not change systemic hemodynamics either before or after
      angioplasty. During angioplasty Hemopump support decreased the pulmonary
      capillary wedge pressure from 23.5 +/- 8.5 mm Hg to 18.6 +/- 7 mm Hg (p = 0.013).
      No changes in either heart rate, mean and systolic aortic pressures, and cardiac
      index were observed throughout the procedure. After successful angioplasty was
      performed, the ratio of proximal to distal flow velocity decreased from 2.11 +/-
      1 to 1.65 +/- 0.2 (p = 0.05). However, Hemopump did not affect absolute coronary
      blood flow velocities or the phasic pattern of flow velocities (diastolic
      systolic velocity ratio, diastolic and systolic velocity integrals) either in
      proximal or distal locations either before or after angioplasty. CONCLUSIONS:
      This study shows that although the 14F Hemopump produces unloading of the left
      ventricle, it does not importantly alter coronary hemodynamics when systemic
      hemodynamics are stable. Whether the Hemopump would maintain or improve coronary
      blood flow in compromised patients remains to be determined.

PMID- 9588416
TI  - Effects of intraaortic balloon counterpulsation on carotid artery blood flow.
AB  - BACKGROUND: The intraaortic balloon pump has been shown to improve cardiac output
      and diastolic coronary flow. Animal studies with balloon counterpulsation have
      shown variable effects on carotid and cerebral blood flow. We investigated the
      effects of counterpulsation with the intraaortic balloon pump on blood flow in
      the common carotid artery in human beings. METHODS AND RESULTS: We studied 14
      patients who had an intraaortic balloon pump placed for clinical indications; 9
      were hypotensive (4 in the setting of an acute myocardial infarction and 5
      immediately after cardiac surgery). Five patients required counterpulsation after
      undergoing complicated coronary angioplasty. Common carotid artery blood flow was
      assessed with carotid Duplex scanning both with and without 1:1 balloon
      augmentation. We found no net increase in the total blood flow in the common
      carotid artery with intraaortic balloon counterpulsation. This result occurred
      despite a significant mean increase in both the peak flow velocity and flow
      velocity integral of the augmented diastolic flows by 160% and 78%, respectively.
      Total flow did not change because an early systolic reversal of blood flow was
      seen only with balloon augmentation, which negated the augmented diastolic flow.
      CONCLUSION: Despite a significant augmentation in diastolic blood flow with
      balloon counterpulsation, no increase occurred in total carotid artery blood
      flow. This appeared to be caused by improper timing of balloon deflation. This
      could result in no improvement in cerebral blood flow with intraaortic balloon
      pump counterpulsation in critically ill patients.

PMID- 9588417
TI  - Effective arterial elastance and the hemodynamic effects of intraaortic balloon
      counterpulsation in patients with coronary heart disease.
AB  - OBJECTIVES: The goal of the present study was to analyze the effects of different
      intraaortic balloon counterpulsation (IABC) inflation volumes on effective
      arterial elastance (Ea) in patients with complicated coronary heart disease and
      to determine whether Ea can predict the hemodynamic response to IABC. BACKGROUND:
      Ea (the central aortic end-systolic pressure to stroke volume ratio) incorporates
      the principal elements of input arterial impedance and has been proved useful to
      evaluate the effects of afterload reduction in patients with left ventricular
      (LV) failure. However, although the hemodynamic action of IABC can be considered
      as a typical example of "pure" afterload reduction, it has never been assessed in
      terms of changes in Ea. METHODS: After clinical stabilization, 18 patients
      treated with IABC for complicated acute myocardial infarction or unstable angina
      were enrolled in the study. Systemic hemodynamics were measured by use of right
      cardiac thermodilution catheters with IABC off (control) and IABC on at balloon
      inflation volumes of 20 and 40 ml, in randomized sequence. Aortic pressure was
      recorded through the central lumen of the IABC catheter to calculate Ea as the
      ratio of aortic dicrotic pressure to stroke volume. RESULTS: A higher control Ea
      was associated with a lower control LV stroke work and a larger IABC-related
      hemodynamic improvement (that was maximal with the 40 ml inflation volume). The
      increase in LV stroke work was closely related to the decrease in Ea.
      Accordingly, hemodynamic benefits from IABC were less evident in patients with
      lower control Ea. In conclusion, effects of IABC were related to both balloon
      inflation volume and control hemodynamics, reflecting the afterload dependence of
      a depressed LV function.

PMID- 9588418
TI  - Cardiac troponin T, creatine kinase, and its isoform release after successful
      percutaneous transluminal coronary angioplasty with or without stenting.
AB  - BACKGROUND: Cardiac troponin T is a sensitive and specific marker for the
      detection of minor myocardial injury. However, it has been rarely used to monitor
      myocardial injury after coronary stenting. The purpose of the study was to
      measure troponin T after apparently successful percutaneous transluminal coronary
      angioplasty (PTCA) with or without coronary stenting and to compare its result
      with serum creatine kinase and its isoform, CKMB. METHODS: The incidence of
      cardiac troponin T elevation was compared with that of creatine kinase or CKMB in
      120 consecutive patients with symptomatic ischemia undergoing visually successful
      PTCA with (n = 59) or without stenting (n = 61). Troponin T, creatine kinase, and
      CKMB were measured before, immediately after, and 18 to 24 hours after the
      procedures were performed. RESULTS: No patient had abnormal troponin T, creatine
      kinase, or CKMB levels before and immediately after the procedures. Moreover, no
      patient showed electrocardiographic evidence of myocardial infarction. Troponin T
      was elevated in 17 patients at 18 to 24 hours after coronary stenting and in
      eight patients after PTCA. Both creatine kinase and CKMB were elevated in five
      patients after coronary stenting and in three patients after PTCA. The frequency
      of abnormal troponin T levels was significantly higher than that of creatine
      kinase or CKMB after coronary interventions (21% vs 6.7%; p < 0.01), and it was
      significantly higher after stenting when compared with angioplasty alone (29% vs
      13%; p < 0.05). Patients with abnormal troponin T levels were more likely to
      undergo repeat revascularization than those without (24% vs 6%; p < 0.01).
      CONCLUSION: Cardiac troponin T is more sensitive than creatine kinase and CKMB in
      detecting minor myocardial injury after coronary interventions. The incidence of
      troponin T release is higher in the patients undergoing stent implantation than
      in patients treated with angioplasty alone.

PMID- 9588419
TI  - Pulmonary embolism: relation between the degree of right ventricle overload and
      the extent of perfusion defects.
AB  - BACKGROUND: Inasmuch as the presence of right ventricle (RV) overload in patients
      with pulmonary embolism (PE) is associated with a bad prognosis, evaluation of RV
      function in PE is of importance. This study was done to establish if the degree
      of RV overload can be predicted from the extent of perfusion defects (PDf).
      METHODS: One hundred twenty-one consecutive patients with PE diagnosed by lung
      scintigraphy (LS) were examined by echocardiography Doppler (ED) immediately
      after diagnosis. PDf were graded visually in categories (LS score 1 = < or =20%,
      2 = >20% of total lung area) and on a continuous scale (normal perfusion = 0, no
      perfusion = 1). The reproducibility of both methods was tested. RV wall motion
      was assessed on a four-point scale (0 = normal to 3 = severely hypokinetic). The
      distance from LV posterior wall to RV anterior wall and dimensions of RV and LV
      were measured. Pulmonary artery systolic pressure (PAsP) was calculated by using
      the maximum velocity of tricuspid regurgitation. RESULTS: There were 51 patients
      with LS score 1 and 70 (58%) with score 2. In comparison with patients with LS
      score 1, those with score 2 more often had RV hypokinesis 2+ or 3+ (n = 49 vs n =
      16) (p < 0.001), larger RV (34 +/- 6 mm [22 to 48] vs 29 +/- 5 [17 to 38]) (SD
      [range]) (p < 0.001) and higher PAsP (51 +/- 13 mm Hg [21 to 83] vs 42 +/- 14 [20
      to 81]) (p < 0.001). The variability in both groups was large. With continuous
      scaling, PDf averaged 0.3. This was also the value that best discriminated RV
      hypokinesis 2+ or 3+ in a receiver operating characteristic curve. However, the
      variability for this scan scoring method was SD 0.073, giving a 95% confidence
      limit of +/-0.15. CONCLUSION: There is a significant correlation between RV
      overload and PDf, but the variability is large; therefore, an estimate of the
      size of perfusion defects in LS cannot replace ED in the assessment of PAsP and
      the degree of RV overload in PE.

PMID- 9588420
TI  - Contrast enhanced and functional magnetic resonance imaging for the detection of
      viable myocardium after infarction.
AB  - PURPOSE: Viable myocardium after acute myocardial infarction may be characterized
      by magnetic resonance imaging (MRI) either by demonstration of recovery of wall
      motion under dobutamine stress or by perfusion patterns after contrast medium
      administration. This study examines the relation between the two techniques.
      MATERIALS AND METHODS: Gradient-echo MRI at rest and under low-dose dobutamine
      stress was performed in 28 patients within the first 2 weeks after acute
      myocardial infarction. In addition, spin-echo MRI was performed after gadolinium
      DOTA administration. Wall motion at rest and under stress was scored to assess
      the contractile reserve of the infarct regions. Infarct enhancement patterns were
      classified as subendocardial, transmural, or as a doughnut pattern. RESULT:
      Subendocardial or absent infarct enhancement was related to functional recovery
      under stress in 31 of 37 infarct segments. Transmural infarct enhancement was
      correlated with the absence of functional recovery in 10 of 17 infarct segments
      (p < 0.002), indicating nonviability. The doughnut pattern was exclusively
      associated with the absence of viability (five of five). CONCLUSION: Contrast
      enhancement patterns are related to residual myocardial viability.

PMID- 9588422
TI  - Platelet activation during dobutamine stress echocardiography.
AB  - BACKGROUND: Dobutamine stress echocardiography (DSE) is a common, useful test for
      the evaluation of coronary artery disease. Two of 650 patients who underwent DSE
      at our institution sustained nonfatal myocardial infarction either during DSE or
      shortly thereafter. Although DSE is associated with low morbidity rates, this
      rate is higher than our experience with exercise treadmill testing (ETT).
      METHODS: Six individuals who did not undergo DSE or ETT were enrolled to evaluate
      direct in vitro effects of dobutamine on platelets. Nine patients undergoing DSE
      and seven patients undergoing ETT were enrolled to evaluate in vivo platelet
      activation. We used flow cytometry and fluorescent-labeled monoclonal antibodies
      to activation-dependent platelet antigens to detect dobutamine-associated
      platelet activation both in vitro and in vivo. RESULTS: In vitro we found a
      synergistic increase in epinephrine-induced CD62 expression in the presence of
      dobutamine. The response to the combination of dobutamine and epinephrine was
      151% to 565% of the expected response. In vivo there was a dose- and time
      dependent rise in the percentage of platelets expressing CD62 in all nine
      subjects undergoing DSE. The median percentage of platelets expressing CD62 was
      1.6% (range 0.1% to 6.8%), 6.5% (range 0.2% to 11.7%), 11.6% (range 5.9% to
      19.1%), and 11.4% (range 7.2% to 25.0%) in the samples obtained at baseline, 20
      microg/kg/min of dobutamine, 40 microg/kg/min of dobutamine, and during the
      recovery phase, respectively (repeated measures analysis of variance, p = 0.02).
      There was no increase in CD62 expression on platelets obtained from seven
      patients at peak ETT. The median percentage of CD62 at baseline ETT was 1.9%
      (range 0.2% to 7.3%) and at peak was 2.6% (range 0.4% to 7.0%) (p = 0.156,
      Wilcoxon signed rank test). CONCLUSION: We conclude that platelet activation
      occurs in vivo in patients undergoing DSE and that this may be caused by a
      synergistic effect of dobutamine with physiologic platelet agonists.

PMID- 9588421
TI  - Cardiovascular stress response and coronary artery disease: evidence of an
      adverse postmenopausal effect in women.
AB  - OBJECTIVES: To test the hypothesis that postmenopausal women demonstrate greater
      vascular instability, measured by enhanced cardiovascular stress responses during
      mental stress, compared with men and premenopausal women. BACKGROUND: Recent data
      suggest that estrogen plays a role in regulating vascular tone. The possible
      consequences of estrogen deficiency during menopause on systemic vascular
      reactivity is largely unexplored. METHODS: One hundred subjects (84 men and 16
      women) underwent mental stress testing with radionuclide ventriculo graphy. Study
      subjects included 19 normal volunteers, 23 control subjects with chest pain
      syndromes or hypertension but without coronary artery disease, and 58 coronary
      artery disease subjects. The subjects performed a series of three mental stress
      tasks, during which hemodynamic data and radionuclide ventriculograms were
      obtained. RESULTS: Overall, women demonstrated greater hemodynamic responses
      during mental stress measured by changes in heart rate, systolic and diastolic
      blood pressure, and double product compared with those of men (all p < 0.05).
      Women with coronary artery disease demonstrated greater heart rate, diastolic
      blood pressure, and double product stress responses than their male counterparts
      (all p < 0.05). Women of postmenopausal age demonstrated significantly greater
      systolic blood pressure reactivity than men or premenopausal women (p < 0.05).
      CONCLUSIONS: Women of postmenopausal age have greater cardiovascular responses to
      stress than men or premenopausal women. These findings suggest an additional
      mechanism by which estrogen deficiency conveys a poor prognosis in female
      patients with coronary artery disease.

PMID- 9588423
TI  - Ability of the exercise electrocardiogram test to detect ischemia in stable
      coronary artery disease patients with ST-segment depression on the resting
      electrocardiogram.
AB  - BACKGROUND: The appearance of ST-segment depression on the exercise
      electrocardiogram (ETT) generally indicates myocardial ischemia. Disorders that
      produce ST-segment depression on the resting electrocardiogram can confound the
      results of the ETT. The purpose of this study was to assess the reliability of
      exercise ST-segment depression as an indicator of ischemia in patients with a
      resting electrocardiographic ST depression, presumably caused by coronary
      disease. METHODS: We studied 882 patients 1 to 6 months after a hospitalization
      for myocardial infarction or unstable angina as part of the Multicenter Study of
      Myocardial Ischemia. An ETT and thallium-201 perfusion scan were performed in all
      patients. For the purpose of this study, the perfusion scan was considered the
      "gold standard" for ischemia. We correlated the ETT ST-segment responses with the
      perfusion scan in a group with a normal electrocardiogram baseline ST segment (NO
      ST DEP group) and in a group with resting electrocardiographic ST depression > or
      =0.5 mm (ST DEP group). RESULTS: Although the frequency of ischemia by perfusion
      scan was similar in the ST DEP group (48%) to that in the NO ST DEP group (40%),
      the ST DEP group had a significantly higher (p = 0.03) sensitivity (54%) in
      detecting ischemia than the NO ST DEP group (35%). The ST DEP group, however, had
      a lower (58% vs 74%) specificity than the NO ST DEP group (p = 0.056). Baseline
      characteristics of the two groups probably account for these differences. The
      overall diagnostic accuracy is similar (58% vs 56%) in the two groups.
      CONCLUSION: We conclude that in a stable population with known coronary disease,
      the presence of ST depression on the resting electrocardiogram does not impair
      the detection of ischemia by the ETT, but may be associated with a higher false
      positive rate.

PMID- 9588424
TI  - Echocardiography and cardiac catheterization in the preoperative assessment of
      ventricular septal defect in infancy.
AB  - BACKGROUND: Cardiac catheterization is commonly performed before repair of
      ventricular septal defect (VSD) in infancy. No study has addressed the accuracy
      of echocardiography alone in defining all of the important anatomic features in
      this population. METHODS: Consecutive infants undergoing VSD repair between 1991
      and 1995 (n = 156) were reviewed. The number of additional VSDs and the presence
      of commonly associated lesions were recorded for each technique and compared with
      a reference standard consisting of a combination of surgical findings plus
      postoperative echocardiography and clinical findings. The associated lesions were
      right ventricular muscle bundles, subaortic ridge, and persistent ductus
      arteriosus. RESULTS: The sensitivity and specificity of echocardiography in the
      detection of additional VSDs was 60% and 99% compared with 53% and 97% for
      cardiac catheterization and 73% and 96% for both techniques. These differences
      were not statistically significant. No differences were seen in the detection of
      commonly associated lesions. CONCLUSION: Routine preoperative cardiac
      catheterization for infants with a primary diagnosis of VSD is probably no longer
      justified.

PMID- 9588425
TI  - Natriuretic peptides: physiology, therapeutic potential, and risk stratification
      in ischemic heart disease.
AB  - BACKGROUND: The natriuretic peptide family consists of four molecules that share
      significant amino acid sequence homologic characteristics and a looped motif.
      Atrial natriuretic peptide and brain natriuretic peptide are similar in their
      ability to promote natriuresis and diuresis, inhibit the renin-angiotensin
      aldosterone axis, and act as vasodilators. Understanding of the actions of C-type
      natriuretic peptide and dendroaspis natriuretic peptide is incomplete, but these
      two new family members also act as vasodilators. Because of the rapid evolution
      of information about this peptide family, we reviewed the state of the art with
      respect to risk stratification and therapeutic ability. METHODS: English-language
      papers were identified by a MEDLINE database search covering 1966 through 1997
      and supplemented with bibliographic references and texts. CONCLUSIONS: The
      natriuretic peptides are counterregulatory hormones with prognostically important
      levels. They are similarly upregulated in heart failure and counteract
      neurohormones that induce vasoconstriction and fluid retention. BNP may be the
      superior prognosticator for risk stratification after myocardial infarction and
      is independent of left ventricular ejection fraction. Lastly, experimental trials
      suggest that administration of exogenous natriuretic peptides or inhibitors of
      their catabolism to patients with ischemic heart disease may be clinically
      beneficial.

PMID- 9588426
TI  - New drug treatments for Alzheimer disease.

PMID- 9588427
TI  - Case of the month: private autopsies.

PMID- 9588428
TI  - Paradigm shifts in coronary artery disease: the old new initiatives.

PMID- 9588429
TI  - Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in
      the era of potent antiretroviral therapy: recommendations of an international
      panel. International AIDS Society-USA.
AB  - OBJECTIVE: To provide recommendations for the treatment of acquired
      immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases,
      including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS:
      A 17-member panel of physicians with expertise in clinical and virological
      research and inpatient care in the field of CMV diseases. EVIDENCE: Available
      clinical and virological study results. Recommendations are rated according to
      the quality and strength of available evidence. Recommendations were limited to
      the treatment of CMV diseases; prophylaxis recommendations are not included.
      PROCESS: The panel was convened in February 1997 and met regularly through
      November 1997. Subgroups of the panel summarized and presented available
      information on specific topics to the full panel; recommendations and ratings
      were determined by group consensus. CONCLUSIONS: Although the epidemiological
      features of CMV diseases are changing in the setting of potent, combination
      antiretroviral therapy, continued attention must be paid to CMV diseases in
      patients infected with the human immunodeficiency virus to prevent irreversible
      endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must
      be individualized based on the characteristics of the lesions, including location
      and extent, specific patient factors, and characteristics of available therapies
      among others. Management of relapse or refractory retinitis must be likewise
      individualized. Ophthalmologic screening for patients at high risk for retinitis
      or who have a prior diagnosis of extraretinal disease is recommended.
      Recommendations for gastrointestinal, pulmonary, and neurologic manifestations
      are included.

PMID- 9588430
TI  - Physician resource use and willingness to participate in assisted suicide.
AB  - OBJECTIVE: To explore the relationship between general internists' tendency to
      conserve medical resources and their willingness to participate in physician
      assisted suicide (PAS). DESIGN AND PARTICIPANTS: Survey of a random sample of
      general internists in 6 urban areas of the United States. MEASUREMENTS: We
      assessed the physicians' use of medical resources by constructing a scale based
      on 6 hypothetical clinical scenarios in which respondents were given a choice
      between resource-intensive and resource-conserving options. We then presented a
      scenario of a competent terminally ill patient with breast cancer making stable
      and persistent requests for PAS. RESULTS: Sixty-seven (33%) of the 206
      respondents indicated that they would participate in the suicide of the depicted
      patient. In a multivariate model, physicians who were more conservative with
      resources were 6.4 times more likely than their resource-intensive counterparts
      to prescribe the requested drugs (P = .02); minority physicians were less willing
      than whites to participate in PAS (odds ratio, 0.34; P = .03). Physicians' number
      of years in practice, location, sex, reported percentage of fee-for-service
      patients, and self-reported strength and direction of financial incentives in the
      respondents' practices were not associated with willingness to prescribe drugs
      for PAS. CONCLUSIONS: Most general internists, especially minority physicians,
      are personally reluctant to participate in PAS. While the characteristics of
      their practices do not affect PAS, physicians who tend to practice resource
      conserving medicine are significantly more likely than their resource-intensive
      counterparts to provide a lethal prescription at the request of a terminally ill
      patient.

PMID- 9588431
TI  - Observations of the treatment of women in the United States with myocardial
      infarction: a report from the National Registry of Myocardial Infarction-I.
AB  - BACKGROUND: To determine whether there are sex differences in the demographics,
      treatment, and outcome of patients with acute myocardial infarction in the United
      States, data from the National Registry of Myocardial Infarction-I from September
      1990 to September 1994 were examined. METHODS: The National Registry of
      Myocardial Infarction-I is a national observational database consisting of 1234
      US hospitals in which each hospital submits data from each patient with acute
      myocardial infarction to a central data collection center. For these analyses,
      the following variables were examined in 354 435 patients with acute myocardial
      infarction: demographics; use of medical therapy including thrombolytic agents;
      use of procedures including cardiac catheterization, percutaneous transluminal
      coronary angioplasty, and coronary artery bypass surgery; length of hospital
      stay; adverse events (stroke, major bleeding, or recurrent myocardial
      infarction); and causes of death. RESULTS: In comparison with men, women
      experiencing acute myocardial infarction in the United States are older, with
      55.7% older than 70 years. Women have a higher mortality rate than men even when
      controlled for age and die less often from arrhythmia but more often from cardiac
      rupture whether or not thrombolytic therapy is used. Treatment with aspirin,
      heparin, or beta-blockers is less frequent in women. When thrombolytic therapy is
      used, women are treated an average of almost 14 minutes later than men and
      experience a greater incidence of major bleeding. Cardiac catheterization,
      percutaneous transluminal coronary angioplasty, and coronary artery bypass
      surgery are used less often in women. CONCLUSIONS: Observations from the National
      Registry of Myocardial Infarction-I document important sex differences in
      demographics, treatment, and outcome of patients with acute myocardial infarction
      in the United States.

PMID- 9588432
TI  - Hip fracture risk in older white men is associated with change in body weight
      from age 50 years to old age.
AB  - BACKGROUND: Change in body weight is a potentially modifiable risk factor for hip
      fracture in older women but, to our knowledge, its relationship to risk in older
      men has not been reported previously. OBJECTIVE: To investigate the effects of
      weight loss and weight gain from age 50 years to old age on the risk of hip
      fracture among elderly men. METHODS: The association between weight change and
      risk of hip fracture was studied in a cohort of 2413 community-dwelling white men
      aged 67 years or older from 3 sites of the Established Populations for
      Epidemiologic Study of the Elderly. RESULTS: The older men in this study,
      observed for a total of 13620 person-years during the 8 years of follow-up,
      experienced 72 hip fractures, yielding an overall incidence rate of 5.3 per 1000
      person-years. Extreme weight loss (> or =10%) beginning at age 50 years was
      associated in a proportional hazards model with increased risk of hip fracture
      (relative risk, 1.8; 95% confidence interval, 1.04-3.3). Weight loss of 10% or
      more was associated with several indicators of poor health, including physical
      disability, low mental status score, and low physical activity (P<.05). Weight
      gain of 10% or more beginning at age 50 years provided borderline protection
      against the risk of hip fracture (relative risk, 0.4; 95% confidence interval,
      0.1-1.00). CONCLUSIONS: Despite differences between older men and women in the
      incidence of and risk factors for hip fracture, weight history is also an
      important determinant of the risk of hip fracture among older men. Weight loss of
      10% or more beginning at age 50 years increases the risk of hip fracture in older
      white men; weight gain of 10% or more decreases the risk of hip fracture. The
      relationship between extreme weight loss and poor health suggests that weight
      loss is a marker of frailty that may increase the risk of hip fracture in older
      men. Physicians should include weight history in their assessment of the risk of
      hip fracture among older men.

PMID- 9588433
TI  - Main risk factors for nephropathy in type 2 diabetes mellitus are plasma
      cholesterol levels, mean blood pressure, and hyperglycemia.
AB  - BACKGROUND: The control of hyperglycemia is of major importance in the treatment
      of patients with type 1 diabetes mellitus. However, there is no consensus about
      the required degree of metabolic control in patients with type 2 diabetes
      mellitus and about the role of hyperglycemia in diabetic nephropathy and in the
      development of atherosclerosis in relation to other risk factors. PATIENTS AND
      METHODS: A prospective, long-term follow-up study was conducted on 574 patients,
      aged 40 to 60 years, with recent onset of type 2 diabetes mellitus. Patients were
      initially normotensive and had normal renal function and a normal urinary albumin
      excretion rate (<30 mg/24 h). The patients were followed up for 2 to 9 years
      (mean +/- SD, 7.8 +/- 0.9 years). Levels of hemoglobin A1c and plasma lipids,
      mean blood pressure, and body mass index (calculated as the weight in kilograms
      divided by the square of the height in meters) were determined periodically.
      Cigarette smoking and socioeconomic status were recorded. Renal status was
      evaluated by the logarithm of the final urinary albumin excretion rate and by the
      decline in reciprocal creatinine values. Definite clinical events including
      death, nonfatal myocardial infarction, angina pectoris, congestive heart failure,
      and peripheral vascular disease were recorded. RESULTS: At the end of the study
      the urinary albumin excretion rate remained normal (<30 mg/24 h) in 373 patients
      (65%), 111 (19%) had microalbuminuria (30-300 mg/24 h), and 90 (16%) had overt
      albuminuria (>300 mg/24 h). Logistic regression models demonstrated that the
      correlation between hemoglobin A1c levels and the risk of albuminuria is
      exponential. Multiple logistic regression analysis indicated that levels of total
      cholesterol, mean blood pressure, and hemoglobin A1c were the main factors
      associated with the decrease in renal function and with the increase in
      albuminuria. The combination of values higher than the 50th percentile of all 3
      factors defined a high-risk patient population. These high-risk patients had an
      odds ratio of 43 (95% confidence interval, 25-106) for microalbuminuria and 15
      (95% confidence interval, 9-25) for clinical events related to arteriosclerosis
      compared with the rest of the group. Low levels of high-density lipoprotein, body
      mass index, cigarette smoking, low socioeconomic status, and male sex were all
      significantly associated with diabetic nephropathy, as well as with the
      manifestations of arteriosclerosis. CONCLUSIONS: The combination of blood
      pressure values in the high-normal range with moderately elevated levels of total
      cholesterol and hemoglobin A1c defines a high-risk group for the progression to
      diabetic nephropathy and for clinical events related to arteriosclerotic
      cardiovascular disease.

PMID- 9588434
TI  - Length of hospital stay for treatment of deep venous thrombosis and the incidence
      of recurrent thromboembolism.
AB  - BACKGROUND: Current guidelines suggest that all patients with acute deep venous
      thrombosis should be treated with intravenous heparin for at least 5 days,
      overlapping with warfarin sodium for 4 to 5 days. METHODS: Using linked state of
      California hospital discharge records from 1991 to 1994 we identified patients
      with acute deep venous thrombosis without pulmonary embolism, and determined the
      6-month cumulative incidence of rehospitalization for recurrent thromboembolism.
      Coding was validated by reviewing the charts of 218 patients matched with the
      statewide data from 4 local hospitals. RESULTS: A total of 36924 linked records
      met study criteria. In the validation group, objectively confirmed thrombosis
      that was treated with intravenous heparin followed by warfarin was noted in 20%,
      65%, 94%, and 95% of the patients who were hospitalized for 2 or fewer days or 3,
      4, or 5 or more days, respectively. Statewide, among patients hospitalized for 3,
      4, 5, and 6 days, the 6-month cumulative incidence of hospitalization for
      recurrent thromboembolism was 5.4%, 5.1%, 5.4%, and 6.0%, respectively.
      Multivariate modeling of patients hospitalized for 3 to 10 days revealed that
      recurrent thromboembolism was associated with the length of hospitalization (odds
      ratio [OR], 1.06 each additional day; 95% confidence interval [CI], 1.04-1.08),
      presence of malignancy (OR, 1.58; 95% CI, 1.46-1.68), age (OR, 0.85 each 10
      years; 95% CI, 0.84-0.86), dementia (OR, 0.38; 95% CI, 0.26-0.49),
      hospitalization for multiple injuries within 3 months (OR, 0.46; 95% CI, 0.32
      0.60), and surgery within 3 months (OR, 0.84; 95% CI, 0.78-0.90). CONCLUSIONS: We
      found no evidence that a stay of 4 days for treatment of deep venous thrombosis
      was associated with a higher rate of recurrent thromboembolism compared with
      hospitalization for 5 or more days. Although the evidence was not as strong, the
      incidence of recurrent thromboembolism after a stay of 3 days appeared comparable
      with that after a stay of 5 days. These findings suggest that fewer than 5 days
      of intravenous heparin overlapping with warfarin may provide effective initial
      treatment for deep venous thrombosis among patients deemed ready for hospital
      discharge.

PMID- 9588436
TI  - Donepezil improves cognition and global function in Alzheimer disease: a 15-week,
      double-blind, placebo-controlled study. Donepezil Study Group.
AB  - BACKGROUND: Donepezil hydrochloride (Aricept) is a selective acetylcholinesterase
      inhibitor developed for the treatment of Alzheimer disease. This phase 3 study
      was 1 of 2 pivotal trials undertaken to establish the efficacy and safety of
      using donepezil in patients with mild to moderately severe Alzheimer disease.
      OBJECTIVES: To further examine the efficacy and safety of using donepezil in the
      treatment of patients with mild to moderately severe Alzheimer disease. To
      examine the relationships between plasma donepezil concentrations, inhibition of
      red blood cell acetylcholinesterase activity, and clinical response. METHODS:
      This was a 12-week, double-blind, placebo-controlled, parallel-group trial with a
      3-week single-blind washout. Outpatients at 23 centers in the United States were
      randomized to receive placebo, 5 mg of donepezil hydrochloride, or 10 mg of
      donepezil hydrochloride (5 mg/d during week 1 then 10 mg/d thereafter)
      administered once daily at bedtime. Primary efficacy was measured using the
      Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and
      Clinician's Interview-Based Impression of Change including caregiver information
      (CIBIC plus). RESULTS: A total of 468 patients entered the study, more than 97%
      of whom were included in the intention-to-treat (end point) analyses. The use of
      donepezil produced statistically significant improvements in ADAS-cog, CIBIC
      plus, and Mini-Mental State Examination scores, relative to placebo. The mean
      drug-placebo differences, at end point, for the groups receiving 5 mg/d and 10
      mg/d of donepezil hydrochloride were, respectively, 2.5 and 3.1 units for ADAS
      cog (P<.001); 0.3 and 0.4 units for CIBIC plus (P< or =.008); and 1.0 and 1.3
      units for Mini-Mental State Examination (P< or =.004). On the CIBIC plus scale,
      32% and 38% of patients, respectively, treated with 5 mg/d and 10 mg/d of
      donepezil hydrochloride demonstrated clinical improvement (a score of 1, 2, or 3)
      compared with placebo (18%). The mean (+/-SEM) donepezil plasma concentrations at
      study end point were 25.9 +/- 0.7 ng/mL and 50.6 +/- 1.9 ng/mL in the groups
      receiving dosages of 5 mg/d and 10 mg/d, respectively. Corresponding mean (+/
      SEM) percentages of inhibition of red blood cell acetylcholinesterase activity
      were 63.9% +/- 0.9% and 74.7% +/- 1.2% for these 2 dosages, respectively. There
      was a statistically significant positive correlation between plasma
      concentrations of donepezil and acetylcholinesterase inhibition; the EC50 (50%
      effect) was obtained at a concentration of 15.6 ng/mL. A plateau of inhibition
      (80%-90%) was reached at plasma donepezil concentrations higher than 50 ng/mL.
      The correlations between plasma drug concentrations and both ADAS-cog (P<.001)
      and CIBIC plus (P = .006) were also statistically significant, as were the
      correlations between red blood cell acetylcholinesterase inhibition and change in
      ADAS-cog (P<.001) and CIBIC plus (P = .005). The incidence of treatment-emergent
      adverse events with both dosages of donepezil (68%-78%) was comparable with that
      observed with placebo (69%). The use of 10 mg/d of donepezil hydrochloride was
      associated with transient mild nausea, insomnia, and diarrhea. There were no
      treatment-emergent clinically significant changes in vital signs or clinical
      laboratory test results. More important, the use of donepezil was not associated
      with the hepatotoxic effects observed with acridine-based cholinesterase
      inhibitors. CONCLUSION: Donepezil hydrochloride (5 and 10 mg) administered once
      daily is a well-tolerated and efficacious agent for treating the symptoms of mild
      to moderately severe Alzheimer disease.

PMID- 9588435
TI  - Sumatriptan injection reduces productivity loss during a migraine attack: results
      of a double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the impact of sumatriptan succinate injection compared
      with placebo on productivity loss during a migraine attack in the workplace.
      DESIGN: Randomized, double-blind, placebo-controlled, parallel-group clinical
      trial. SETTING: Fifteen clinical centers in the United States. PATIENTS: One
      hundred thirty-five patients 18 years and older diagnosed as having migraine
      according to International Headache Society criteria. INTERVENTIONS: Patients
      self-administered sumatriptan injection (6 mg) or matching placebo to treat a
      moderate or severe migraine occurring within the first 4 hours of a minimum 8
      hour work shift. MAIN OUTCOME MEASURES: Mean productivity loss 2 hours after
      dosing and across the work shift; percentages of patients returning to normal
      work performance within 2 hours after dosing and across the work shift;
      percentages of patients experiencing headache relief (reduction of moderate or
      severe predose pain to mild or no pain) 1 and 2 hours after dosing. RESULTS: Mean
      productivity loss was significantly (P< or =.002) lower in the sumatriptan group
      compared with the placebo group both during the 2-hour postdose period
      (sumatriptan, 39 minutes; placebo, 54 minutes) and across the work shift
      (sumatriptan, 86 minutes; placebo, 168 minutes). Significantly (P<.001) greater
      percentages of patients in the sumatriptan group compared with the placebo group
      returned to normal work performance by 2 hours after dosing (sumatriptan, 52%;
      placebo, 9%) and across the work shift (sumatriptan, 66%; placebo, 18%).
      Significantly (P< or =.001) greater percentages of patients in the sumatriptan
      group compared with the placebo group experienced headache relief 1 hour after
      dosing (sumatriptan, 69%; placebo, 18%) and 2 hours after dosing (sumatriptan,
      79%; placebo, 32%). CONCLUSION: Sumatriptan reduced migraine-associated
      productivity loss during a minimum 8-hour work shift by approximately 50%
      compared with placebo and alleviated headache in more than three fourths of
      patients.

PMID- 9588437
TI  - Septic shock from Mycobacterium tuberculosis after therapy for Pneumocystis
      carinii.
AB  - Septic shock resulting from Mycobacterium tuberculosis (TB) occurs only rarely,
      even among patients infected with human immunodeficiency virus. We report a case
      of fulminant TB sepsis in the setting of human immunodeficiency virus infection.
      This case illustrates the hazards of corticosteroid use as a part of empirical
      treatment of Pneumocystis carinii pneumonia, as well as the unique appearance of
      TB on chest x-ray films.

PMID- 9588438
TI  - Risk of animal contact in immunocompromised hosts.

PMID- 9588439
TI  - Multimodality evoked potentials in the diagnosis and management of neurological
      sarcoidosis.

PMID- 9588440
TI  - The metabolically obese, normal-weight individual revisited.
AB  - Nearly 20 years ago, it was suggested that individuals exist who are not obese on
      the basis of height and weight, but who, like people with overt obesity, are
      hyperinsulinemic, insulin-resistant, and predisposed to type 2 diabetes,
      hypertriglyceridemia, and premature coronary heart disease. Since then it has
      become increasingly clear that such metabolically obese, normal-weight (MONW)
      individuals are very common in the general population and that they probably
      represent one end of the spectrum of people with the insulin resistance syndrome.
      Available evidence also suggests that MONW individuals could account for the
      higher prevalence of type 2 diabetes, cardiovascular disease, and other disorders
      in people with a BMI in the 20-27 kg/m2 range who have gained modest amounts of
      weight (2-10 kg of adipose mass) in adult life. Specific factors that appear to
      predispose MONW, as well as more obese individuals, to insulin resistance include
      central fat distribution, inactivity, and a low VO2max. Because these factors are
      potentially reversible and because insulin resistance may contribute to the
      pathogenesis of many diseases, it is our premise that a compelling argument can
      be made for identifying MONW individuals and treating them with diet, exercise,
      and possibly pharmacological agents before these diseases become overt, or at
      least early after their onset. One reason for doing so is that disorders such as
      type 2 diabetes may be accompanied by irreversible consequences, e.g., ischemic
      heart disease and nephropathy, at the time of diagnosis or shortly thereafter.
      Another is that MONW individuals in general should be younger and more amenable
      and responsive to diet and exercise therapy than are obese patients with
      established disease. That long-term diet and exercise can work is suggested by
      two large studies in which, over 5-6 years, the incidence of diabetes was
      diminished in nonobese and minimally obese patients with impaired glucose
      tolerance. Based on these considerations and the emerging worldwide epidemic of
      type 2 diabetes, we believe that studies to assess whether therapies aimed at
      young MONW individuals can prevent the development of type 2 diabetes and other
      diseases, including perhaps obesity itself, are urgently needed.

PMID- 9588441
TI  - Role of portal insulin delivery in the disappearance of intravenous glucose and
      assessment of insulin sensitivity.
AB  - The contribution of portal insulin delivery to the disappearance of glucose
      administered intravenously was assessed in the present study. Paired insulin
      modified intravenous glucose tolerance tests (IVGTTs) were performed in dogs in
      which insulin was administered into the portal vein or into a peripheral vein.
      Peripheral insulin levels were matched in the paired IVGTTs by adjusting the
      portal insulin dose in proportion to first-pass hepatic insulin extraction. Two
      sets of IVGTTs were performed. In the first set, hepatic insulin extraction was
      assumed to be 50% (insulin doses of 0.03 U/kg portal and 0.015 U/kg peripheral; n
      = 6); in the second set, the assumed extraction rate was reduced to 33% (0.0225
      U/kg portal and 0.015 U/kg peripheral; n = 8). In the second set of experiments,
      a control "zero" dose (no insulin injection) was also performed. For these latter
      three IVGTTs, the exogenous glucose bolus was labeled with 3-[3H]glucose (25
      microCi) to separately assess insulin's effects on the rate of glucose
      disappearance (Rd) and endogenous glucose production (EGP). For the paired IVGTT
      based on 33% extraction, the area under the insulin curves after the portal
      insulin injection was within 2% of that observed with peripheral insulin
      injection (1,820 +/- 711 vs. 1,791 +/- 661 microU/ml min; P = 0.79). For these
      conditions, neither the glucose profiles nor the minimal model estimate of
      insulin sensitivity (S(I)) was significantly influenced by the higher portal
      insulin delivery (S(I): 3.69 +/- 0.56 vs. 3.35 +/- 0.60 10(-4) min(-1) per
      microU/ml; portal vs. peripheral; P > 0.05). Analysis of the 3-[3H]glucose tracer
      dynamics failed to reveal any differences in the portal versus peripheral insulin
      effect on glucose disappearance or production. We conclude that portal insulin
      delivery per se does not significantly affect insulin's ability to normalize
      plasma glucose during acute glucose challenges.

PMID- 9588442
TI  - Short-term exposure to tumor necrosis factor-alpha does not affect insulin
      stimulated glucose uptake in skeletal muscle.
AB  - It has been hypothesized that increased production of tumor necrosis factor-alpha
      (TNF-alpha) plays a role in causing the insulin resistance associated with
      obesity. Obesity with insulin resistance is associated with increased production
      of TNF-alpha by fat cells. Exposure of 3T3-L1 adipocytes to TNF-alpha for 3-4
      days makes them insulin resistant. TNF-alpha has also been reported to rapidly
      (15-60 min) cause insulin resistance, with a decrease in insulin-stimulated
      tyrosine phosphorylation, in a number of cultured cell lines. Because skeletal
      muscle is the major tissue responsible for insulin-stimulated glucose disposal,
      we performed the present study to determine if acute exposure to TNF-alpha causes
      insulin resistance in muscle. We found that exposure of soleus muscles to 6
      nmol/l TNF-alpha for 45 min in vitro had no inhibitory effect on insulin
      stimulated tyrosine phosphorylation of the insulin receptor or insulin receptor
      substrate 1 (IRS-1) or on phosphatidylinositol 3-kinase association with IRS-1.
      Incubation of epitrochlearis and soleus muscles with 6 nmol/l TNF-alpha for 45
      min or 4 h had no effect on insulin-stimulated 2-deoxyglucose (2-DG) uptake.
      Treatment of epitrochlearis muscles with 2 nmol/l TNF-alpha for 8 h also had no
      effect on insulin-stimulated 2-DG uptake. We conclude that in contrast to Fao
      hepatoma cells and 3T3-L1 fibroblasts, skeletal muscle does not become insulin
      resistant in response to short-term exposure to TNF-alpha.

PMID- 9588443
TI  - Human islets of Langerhans express Fas ligand and undergo apoptosis in response
      to interleukin-1beta and Fas ligation.
AB  - IDDM results from a progressive loss of pancreatic beta-cells that, in humans,
      may be triggered by a combination of genetic and environmental factors. Recently,
      attention has been focused on the hypothesis that the loss of beta-cells is
      initiated by inappropriate induction of apoptosis. We now demonstrate that human
      islets of Langerhans undergo apoptosis upon exposure to interleukin-1beta. The
      cytokine also sharply increases the number of cells that enter apoptosis on
      treatment with a stimulatory anti-Fas antibody. Western blotting and
      immunocytochemistry clearly show for the first time that human pancreatic beta
      cells normally express Fas ligand. The results suggest that human islet cells are
      primed to undergo apoptosis by interleukin-1beta and that this involves the close
      association between cell-surface Fas and its ligand.

PMID- 9588444
TI  - Definition of multiple ICA512/phogrin autoantibody epitopes and detection of
      intramolecular epitope spreading in relatives of patients with type 1 diabetes.
AB  - The related tyrosine phosphatase-like proteins, islet cell antigen 512 (ICA512)
      and phosphatase homologue in granules of insulinoma (phogrin), are major targets
      of autoantibodies in patients with type 1 diabetes. In the current study, we have
      examined the overlapping specificities and antigenic epitopes of autoantibodies
      to ICA512 and phogrin and determined whether intramolecular epitope spreading
      occurs during the development of diabetic autoimmunity. ICA512 autoantibodies and
      phogrin autoantibodies were detected in 65-70% (n = 110) of patients with new
      onset type 1 diabetes and 60-65% (n = 42) of prediabetic relatives of patients
      with type 1 diabetes. Of the sera, 10% reacted with ICA512 but not phogrin,
      whereas only 1% of sera reacted with phogrin but not ICA512. The binding of
      phogrin autoantibodies in 88 dual (ICA512 and phogrin) autoantibody-positive sera
      could be completely blocked by excess recombinant ICA512, whereas the blocking of
      ICA512 autoantibodies with recombinant phogrin was only partial (mean inhibition
      of 58.9 +/- 3.7%, mean +/- SE). Binding and competition analysis using multiple
      chimeric ICA512/phogrin constructs demonstrated that a major unique epitope for
      ICA512 autoantibodies is localized to amino acids 762-887. A conformational
      epitope associated with the carboxy-terminal 31 amino acids of ICA512 was
      recognized by one-third of sera, and a minor epitope is located on amino acids
      601-762 of ICA512. The major epitopes for phogrin-selective autoantibodies were
      localized to amino acids 640-922 of phogrin. Sequential serum samples were
      analyzed in 22 relatives who expressed ICA512/phogrin autoantibodies.
      Intramolecular epitope spreading was found for 5 of 13 relatives who have
      progressed to type 1 diabetes. Among nine relatives who have remained
      nondiabetic, three demonstrated a decrease in the number of epitopes recognized.
      These studies highlight the complexity of autoantibody recognition of
      ICA512/phogrin and are consistent with the hypothesis that ICA512/phogrin may be
      recognized as a consequence of beta-cell destruction.

PMID- 9588445
TI  - Islet amyloid-associated diabetes in obese A(vy)/a mice expressing human islet
      amyloid polypeptide.
AB  - We have previously shown that hemizygous transgenic mice expressing human islet
      amyloid polypeptide (hIAPP) in pancreatic beta-cells have no diabetic phenotype,
      whereas in the homozygous state, they developed severe, early-onset hyperglycemia
      associated with impaired insulin secretion and beta-cell death. We investigated
      the possibility that when the hemizygous mice are crossed onto an obese, insulin
      resistant strain such as agouti viable yellow (A(vy)/a), they would exhibit a
      phenotype more akin to human type 2 diabetes. The hIAPP-expressing A(vy) males
      (TG-Y) displayed fasting hyperglycemia at 90 days of age and by 1 year progressed
      to severe hyperglycemia relative to their nontransgenic counterparts. Plasma
      insulin concentrations and pancreatic insulin content dropped 10- to 20-fold,
      suggesting severe impairment of beta-cell function. Histopathological findings
      revealed beta-cell degeneration and loss consistent with the drop in the plasma
      insulin concentration. In addition, large deposits of IAPP amyloid were present
      in TG-Y islets. We conclude that in transgenic mice expressing hIAPP, insulin
      resistance can induce overt, slow-onset diabetes associated with islet amyloid
      and decreased beta-cell mass.

PMID- 9588446
TI  - Identification of alpha- and beta-cells in intact isolated islets of Langerhans
      by their characteristic cytoplasmic Ca2+ concentration dynamics and
      immunocytochemical staining.
AB  - Ratiometric images of cytoplasmic Ca2+ concentration ([Ca2+]c) in individual
      cells were recorded simultaneously with a confocal ultraviolet-laser microscope
      in the Indo-1-loaded islets isolated from mice. After changes in [Ca2+]c in
      response to glucose or amino acids were recorded, the islet was fixed,
      permeabilized, and stained by the indirect immunofluorescence method against
      insulin or glucagon in situ; the individual cells were then identified in the
      focal plain identical to that used for the [Ca2+]c imaging. Almost all cells
      identified as insulin-positive (beta-cells) by their distinct immunofluorescence
      responded to the increase in glucose concentration from 3 to 11 mmol/l with an
      increase in [Ca2+]c. Major populations of cells (approximately 65%) identified as
      glucagon-positive (alpha-cells) responded to the addition of arginine (5-10
      mmol/l) to 3 mmol/l glucose solution with an increase in [Ca2+]c. About half of
      the alpha-cells (47.6%) responded to the addition of alanine (5-10 mmol/l) to 3
      mmol/l glucose solution with an increase in [Ca2+]c. In contrast, <13% of beta
      cells responded to the addition of alanine (5-10 mmol/l) or arginine (5-10
      mmol/l) to 3 mol/l glucose with an increase in [Ca2+]c. More than one-fourth of
      alpha-cells responded with an increase in [Ca2+]c when glucose concentration in
      perifusion solution was reduced from 11 to 0 mmol/l. These results indicate that
      [Ca2+]c changes in islet cells stimulated by glucose or amino acid were
      characteristic of the cell species, at least in the alpha- and beta-cell. This
      technique provides a useful tool to investigate not only the intracellular signal
      transduction but also the intercellular signal transmission in the intact islet.

PMID- 9588447
TI  - Glucose activates both K(ATP) channel-dependent and K(ATP) channel-independent
      signaling pathways in human islets.
AB  - Insulin secretion by isolated islets of Langerhans from 19 human donors (9 women
      and 10 men) was studied in vitro to test the hypothesis that human islets contain
      both the K(ATP) channel-dependent and the K(ATP) channel-independent signaling
      pathways. The results demonstrated the presence of both of these major pathways
      of glucose signaling. Thus, insulin secretion was stimulated by high glucose
      concentrations, by the sulfonylurea tolbutamide, and by a depolarizing
      concentration of potassium chloride. Diazoxide, which activates the K(ATP)
      channel, completely blocked the stimulation of release by glucose. Stimulation of
      insulin release by tolbutamide, which inhibits the K(ATP) channel and depolarizes
      the beta-cell, and inhibition of glucose-stimulated release by diazoxide, which
      activates the channel and repolarizes the beta-cell, confirm the involvement of
      the K(ATP) channel-dependent pathway in glucose signaling. The participation of
      the K(ATP) channel-independent pathway in the stimulation of insulin release by
      glucose was demonstrated for the first time in human islets. This was done in two
      ways. The first method, in the presence of diazoxide, blocked the action of
      glucose on the K(ATP) channel in combination with a depolarizing concentration of
      KCl to raise [Ca2+]i. Under these conditions, glucose stimulated insulin release.
      A second method to demonstrate the involvement of the K(ATP) channel-independent
      pathway was to close the K(ATP) channels with tolbutamide. Again, with no
      possibility of further action on the K(ATP) channel, glucose stimulated insulin
      release. In a final series of experiments, glucose-stimulated insulin release was
      profoundly inhibited by somatostatin, clonidine, and prostaglandin E2, but not by
      galanin.

PMID- 9588448
TI  - Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of
      glucagon-like peptide 1 in the anesthetized pig.
AB  - Glucagon-like peptide 1 (GLP-1) has been proposed as a new therapeutic agent in
      the management of diabetes because of its glucose-dependent stimulation of
      insulin secretion, but this is limited by its rapid degradation in vivo by
      dipeptidyl peptidase IV (DPP IV). In nonfasted anesthetized pigs, valine
      pyrrolidide (a stable and selective inhibitor of DPP IV), at a dose that reduced
      plasma DPP IV activity by more than 90%, increased both the amount of intact GLP
      1 in the basal state (from 5 +/- 1 to 18 +/- 7 pmol/l; P < 0.05) and the
      proportion remaining undegraded during an infusion (from 21.0 +/- 1.3 to 102.3 +/
      4.5%; P < 0.0001). This was associated with a prolonged plasma half-life for the
      intact peptide (from 1.0 +/- 0.1 to 3.2 +/- 0.2 min; P < 0.0005). In the basal
      (nonfasted) state, valine-pyrrolidide potentiated the effect of intravenous GLP-1
      on the incremental area under the curve (AUC) for glucose (-0.50 +/- 0.91 to 
      2.83 +/- 0.59 20 min x mmol x l(-1); P < 0.05) and insulin (23.8 +/- 30.5 to
      332.5 +/- 99.6 20 min x pmol x l(-1); P < 0.05). When an intravenous glucose load
      was given during the GLP-1 infusion, valine-pyrrolidide augmented the insulin
      response (AUC, 2,086.2 +/- 600.9 to 6,247.0 +/- 1443.9 40 min x pmol x l(-1); P <
      0.05). These results suggest that by reducing GLP-1 degradation, DPP IV
      inhibition potentiates the insulinotropic effect of GLP-1 and may, therefore, be
      a viable approach to the management of diabetes.

PMID- 9588449
TI  - Development of insulin resistance in the JCR:LA-cp rat: role of triacylglycerols
      and effects of MEDICA 16.
AB  - The JCR:LA-cp rat develops an extreme obese/insulin-resistant syndrome such that
      by 12 weeks of age, there is no longer any insulin-mediated glucose turnover. At
      4 weeks of age, obese and lean rats have essentially identical basal and insulin
      mediated glucose uptake in skeletal muscle. By 8 weeks of age, however, the obese
      rats no longer exhibit such intake. Plasma insulin concentrations in the normal
      fed state show only small increases up to 4 weeks, with a rapid rise to a marked
      hyperinsulinemia thereafter, with an age at half-development of 5.5 weeks. Plasma
      triacylglycerol concentrations in fed obese rats are elevated at 3 weeks and rise
      rapidly thereafter. The triacylglycerol content of skeletal muscle is
      significantly elevated in the obese rats at 4 weeks of age. Histological
      examination of Oil Red O-stained muscle tissue and transmission electron
      microscopy shows the presence of intracellular lipid droplets. Treatment with the
      potent triacylglycerol-lowering agent MEDICA 16 (beta,beta'
      tetramethylhexadecanedioic acid) from 6 weeks of age reduces plasma lipids
      markedly, but it reduces body weight and insulin resistance only modestly. In
      contrast, treatment with MEDICA 16 from the time of weaning at 3 weeks of age
      results in the normalization of food intake and body weight to over 8 weeks of
      age. The development of hyperinsulinemia is also delayed until 8.5 weeks of age,
      and insulin levels remain strongly reduced. Plasma triacylglycerol concentrations
      remain at the same level as in lean rats, and neither an elevated muscle
      triacylglycerol content nor intracellular lipid droplets are found at 4 weeks of
      age. The results indicate that insulin resistance develops in the young animals
      and is not directly due to a genetically determined defect in insulin metabolism.
      The mechanism of induction instead appears to be related to an exaggerated
      triacylglycerol metabolism.

PMID- 9588451
TI  - Obesity-independent hyperinsulinemia in nondiabetic first-degree relatives of
      individuals with type 2 diabetes.
AB  - A close association between obesity and hyperinsulinemia is well recognized, but
      it is not known whether this relationship is affected by the genetic
      susceptibility to type 2 diabetes. Insulin response to a 75-g oral glucose load
      was evaluated in healthy nondiabetic Caucasians with first-degree family history
      of diabetes (relatives, n = 55) and those without family history (nonrelatives, n
      = 33). A significant correlation between the BMI and insulin response (area under
      the curve [AUC] during the 2-h period) was seen in nonrelatives (r = 0.68, P <
      0.0001) but not in the relatives (r = 0.12, P = 0.37). Multivariate analysis
      revealed that obesity (BMI) was the primary determinant of insulin response in
      nonrelatives (P < 0.001), whereas among the relatives, BMI had no significant
      impact (P = 0.28). Thus, these distinctions between the relatives and
      nonrelatives remained after adjusting for glucose level, age, and gender. Among
      first-degree relatives, the commonly observed association between BMI and insulin
      response is lost, and hyperinsulinemia is present even in the absence of obesity.
      First-degree family history of diabetes may confer insulin resistance that is
      independent of obesity. Alternatively, this could suggest a pathological
      regulation of an obesity-insulin feedback loop, e.g., a defective recognition of
      adiposity.

PMID- 9588450
TI  - Effects of insulin and acipimox on VLDL1 and VLDL2 apolipoprotein B production in
      normal subjects.
AB  - The objective of the study was to examine the potential differential effect of
      insulin and acipimox (both of which reduce free fatty acid [FFA] availability) on
      VLDL apolipoprotein (apo) B metabolism. We studied eight healthy men (age 40 +/-
      4 years, BMI 25.8 +/- 0.9 kg/m2, plasma triglycerides 1.30 +/- 0.12 mmol/l) after
      an overnight fast (control study, n = 8), during inhibition of lipolysis with an
      antilipolytic agent, acipimox (n = 8), and under 8.5-h euglycemic
      hyperinsulinemic conditions (n = 5). Plasma FFAs were similarly suppressed in the
      acipimox and insulin studies (approximately 70% suppression). 2H3-leucine was
      used to trace apo B kinetics in VLDL1 and VLDL2 subclasses (Svedberg flotation
      rates: 60-400 and 20-60), and a non-steady-state multicompartmental model was
      used to derive the kinetic constants. The mean rate of VLDL1 apo B production was
      708 +/- 106 mg/day at the beginning and 602 +/- 140 mg/day at the end of the
      control study. Production of the lipoprotein decreased to 248 +/- 93 mg/day
      during the insulin study (P < 0.05 vs. control study) and to 375 +/- 92 mg/day
      (NS) during the acipimox study. Mean VLDL2 apo B production was significantly
      increased during the acipimox study (399 +/- 42 vs. 236 +/- 27 mg/day, acipimox
      vs. control, P < 0.05) but not during the insulin study (332 +/- 51 mg/day, NS).
      The fractional catabolic rates of VLDL1 and VLDL2 apo B were similar in all three
      studies. We conclude that acute lowering of FFAs does not change the overall
      production rate of VLDL particles, but there is a shift toward production of
      smaller and denser VLDL2 particles, and, thus, the amount of total VLDL particles
      secreted remained constant. Insulin acutely suppresses the total production rate
      of VLDL apo B by decreasing the production of large triglyceride-rich VLDL1
      particles. Based on these findings, we postulate that insulin has a direct
      suppressive effect on the production of VLDL apo B in the liver, independent of
      the availability of FFAs.

PMID- 9588452
TI  - Microalbuminuria is associated with insulin resistance in nondiabetic subjects:
      the insulin resistance atherosclerosis study.
AB  - Microalbuminuria is associated with excess cardiovascular mortality in both
      diabetic and nondiabetic subjects. Patients with NIDDM and microalbuminuria are
      more insulin resistant than those without microalbuminuria. However, the
      relationship between insulin resistance and microalbuminuria in patients with
      NIDDM could be due to hyperglycemia, which can cause both insulin resistance and
      an increase in albumin excretion rate. Little is known about microalbuminuria and
      insulin resistance in nondiabetic subjects. Therefore, we examined, cross
      sectionally, the relationship of insulin sensitivity (S(I) x 10(-4) min x microU(
      1) x ml(-1)), estimated by a frequently sampled intravenous glucose tolerance
      test and the minimal model and fasting plasma insulin concentration, to
      microalbuminuria (albumin-to-creatinine ratio > or = 2 mg/mmol) in 982
      nondiabetic subjects aged 40-69 years. Altogether, 15% of the subjects had
      microalbuminuria, and 32% had hypertension. Subjects with microalbuminuria had a
      lower degree of insulin sensitivity (means +/- SE, 1.70 +/- 0.11 vs. 2.25 +/-
      0.07, P = 0.003) and higher fasting insulin concentrations (17.4 +/- 1.1 vs. 15.7
      +/- 0.5 mU/l, P = 0.059) compared with subjects without microalbuminuria. In
      logistic regression analysis, an increasing degree of insulin sensitivity was
      related to a decreasing prevalence of microalbuminuria (odds ratio = 0.86, 95%
      CI: 0.79-0.94, P < 0.001). Although this relationship attenuated after adjustment
      for age, sex, ethnicity, hypertension, fasting glucose, and BMI, it still
      remained significant. The association between insulin sensitivity and
      microalbuminuria was shown not to be different between normotensive and
      hypertensive subjects. Our results suggest a relationship between insulin
      resistance and microalbuminuria in nondiabetic subjects that is partially
      dependent on blood pressure, glucose levels, and obesity.

PMID- 9588453
TI  - Glucose-induced oxidative stress in vascular contractile cells: comparison of
      aortic smooth muscle cells and retinal pericytes.
AB  - Free radical-mediated damage to vascular cells may be involved in the
      pathogenesis of diabetic vasculopathy. The aim of this study was to compare the
      extent of glucose-induced oxidative stress in both vascular smooth muscle cells
      (VSMCs) and pericytes and the effect on antioxidant enzyme gene expression and
      activities. Porcine aortic VSMC and retinal pericytes were cultured in either 5
      or 25 mmol/l glucose for 10 days. Intracellular malondialdehyde (MDA) was
      measured as a marker of peroxidative damage, and mRNA expression of CuZn-SOD,
      MnSOD, catalase, and glutathione peroxidase (GPX) were measured by Northern
      analysis. Glutathione (GSH) was also measured. There was a significant increase
      in MDA in VSMCs in 25 mmol/l glucose (1.34 +/- 0.11 vs. 1.88 +/- 0.24 nmol/mg
      protein, 5 vs. 25 mmol/l D-glucose, mean +/- SE, n = 15, P < 0.01), but not in
      pericytes (0.38 +/- 0.05 vs. 0.37 +/- 0.05 nmol/mg protein, n = 11). There was a
      significant decrease in GSH in both cell types (VSMC, 1.40 +/- 0.13 vs. 0.69 +/-
      0.12 nmol/mg protein, n = 15, P < 0.001; pericytes, 1.97 +/- 0.17 vs. 0.94 +/-
      0.16 nmol/mg protein, n = 11, P < 0.001). mRNA expression of CuZnSOD and MnSOD
      was increased only in VSMCs (by 58.5 +/- 8.1 and 41.0 +/- 6.9%, respectively, n =
      8, P < 0.01). CuZnSOD protein was increased by approximately 120% (P < 0.00001).
      None of the antioxidant enzyme activities was altered between 5 and 25 mmol/l
      glucose in either cell type. Both MnSOD activities and GSH concentrations were
      higher in pericytes compared with VSMC under basal (5 mmol/l) conditions (P <
      0.05 and P < 0.02, respectively). These results demonstrate glucose-induced
      reduction of GSH in both cells, but only in VSMC is there evidence of oxidant
      damage in the form of lipid peroxidation, implying significant differences in
      intracellular responses to glucose between contractile cells in the macro- and
      microvasculature.

PMID- 9588454
TI  - Differential vasoactive effects of the insulin sensitizers rosiglitazone (BRL
      49653) and troglitazone on human small arteries in vitro.
AB  - BRL 49653 (rosiglitazone) and troglitazone are thiazolidinedione insulin
      sensitizing agents, which are undergoing clinical evaluation as treatments for
      NIDDM. Potential side effects of thiazolidinediones include edema and
      hemodilution. Although the underlying mechanisms are presently unclear, animal
      and human studies have demonstrated a vasodilator action of troglitazone, which
      could in theory cause fluid retention. This in vitro study compared the direct
      vasodilator effects of troglitazone and BRL 49653 in small arteries (n = 44) from
      human subcutaneous fat. In arterial rings with a functioning endothelium and
      preconstricted with norepinephrine (NE; 6 micromol/l), troglitazone (n = 22
      vessels), but not BRL 49653 (1-100 micromol/l), caused a concentration-related
      relaxation (69.4 +/- 5.2% at 100 micromol/l; P < 0.01). In the presence of
      indomethacin (IM; 10 micromol/l; n = 12), this vasorelaxant effect of
      troglitazone was abolished (P < 0.01 vs. troglitazone alone) and replaced by
      enhanced vasoconstriction (58.5 +/- 39.5% over the NE baseline) similar in
      magnitude to that produced by troglitazone vehicle (ethanol) alone (n = 16; NS
      vs. ethanol vehicle). By contrast, BRL 49653 (100 micromol/l; n = 22) and an
      equivalent volume of ethanol alone (n = 12) caused similar degrees of
      vasoconstriction (18.7 +/- 14.6 and 22.5 +/- 8.0%, respectively; NS). In the
      presence of IM (10 micromol/l; n = 10), the vasoconstrictor effect of BRL 49653
      was enhanced (41.5 +/- 14.4%), although not significantly (NS vs. BRL 49653 alone
      or ethanol alone). Additional studies in Wistar rat arteries showed a similar
      vasodilator effect of troglitazone that was not inhibited by L-NAME (100
      micromol/l). The alpha-tocopherol moiety alone had no vasorelaxant effect at
      concentrations up to 300 micromol/l. Thus, in human arterial resistance vessels
      in vitro, BRL 49653 does not possess the direct, IM-sensitive vasorelaxant action
      of troglitazone. This vasodilation could, in theory, permit transmission of
      systemic pressure to the capillary bed.

PMID- 9588455
TI  - Glial reactivity and impaired glutamate metabolism in short-term experimental
      diabetic retinopathy. Penn State Retina Research Group.
AB  - The early pathophysiology of diabetic retinopathy and the involvement of neural
      and vascular malfunction are poorly understood. Glial cells provide structural
      and metabolic support for retinal neurons and blood vessels, and the cells become
      reactive in certain injury states. We therefore used the streptozotocin rat model
      of short-term diabetic retinopathy to study glial reactivity and other glial
      functions in the retina in the first months after onset of diabetes. With a two
      site enzyme-linked immunosorbent assay, we measured the expression of the
      intermediate filament glial fibrillary acidic protein (GFAP). After 1 month, GFAP
      was largely unchanged, but within 3 months of the beginning of diabetes, it was
      markedly induced, by fivefold (P < 0.04). Immunohistochemical staining showed
      that the GFAP induction occurred both in astrocytes and in Muller cells.
      Consistent with a glial cell malfunction, the ability of retinas to convert
      glutamate into glutamine, assayed chromatographically with an isotopic method,
      was reduced in diabetic rats to 65% of controls (P < 0.01). Furthermore, retinal
      glutamate, as determined by luminometry, increased by 1.6-fold (P < 0.04) after 3
      months of diabetes. Taken together, these findings indicate that glial reactivity
      and altered glial glutamate metabolism are early pathogenic events that may lead
      to elevated retinal glutamate during diabetes. These data are the first
      demonstration of a specific defect in glial cell metabolism in the retina during
      diabetes. These findings suggest a novel understanding of the mechanism of neural
      degeneration in the retina during diabetes, involving early and possibly
      persistent glutamate excitotoxicity.

PMID- 9588456
TI  - Sib-pair linkage analysis for susceptibility genes for microvascular
      complications among Pima Indians with type 2 diabetes. Pima Diabetes Genes Group.
AB  - The aim of this study was to identify loci influencing susceptibility to
      microvascular complications (nephropathy and retinopathy) in Pima Indians with
      type 2 diabetes. Affected sib-pair linkage analyses were performed on 98 diabetic
      sibling pairs with nephropathy in both members and on 103 sibling pairs with
      retinopathy in both members. Four chromosomal regions with some evidence of
      linkage (P < 0.01; logarithm of odds [LOD] >1.18) with nephropathy were
      identified. The strongest evidence for linkage with nephropathy was on chromosome
      7, where two adjacent markers, D7S500 and D7S1804, were linked both by two-point
      analysis (LOD = 2.73 and LOD = 2.28; respectively) and by multipoint analysis
      (LOD = 2.04). Additional loci potentially linked to nephropathy were found on
      chromosome 3, near D3S3053 (multipoint LOD = 1.48); on chromosome 9, near D9S910
      (multipoint LOD = 1.12) and D9S302 (two-point LOD = 1.28); and on chromosome 20,
      near D20S115 (multipoint LOD = 1.83) and GATA65E01 (two-point LOD = 1.89).
      Multipoint analyses showed two regions with some evidence for linkage to
      retinopathy: chromosome 3 between D3S3053 and D3S2427 (LOD = 1.36), and
      chromosome 9 between D9S1120 and D9S910 (LOD = 1.46). These linkage analyses
      suggest that a genetic element on chromosome 7 and possibly one on chromosome 20
      influence susceptibility to diabetic nephropathy but not retinopathy. Genetic
      elements on chromosome 3 and 9 may determine susceptibility to both these
      complications. These loci could presumably influence susceptibility to the
      complications by influencing the microvasculature directly, by influencing the
      severity of hyperglycemia, or by other unknown mechanisms.

PMID- 9588457
TI  - A functional analysis of the role of IGF2 in IDDM2-encoded susceptibility to type
      1 diabetes.
AB  - Genetic studies have identified a number of loci demonstrating linkage to type 1
      diabetes. One of the largest single contributors to genetic susceptibility, after
      the major histocompatability complex, is the IDDM2 locus, which maps to a
      nontranscribed variable number of tandem repeats (VNTR) minisatellite upstream of
      the insulin (INS) and insulin-like growth factor 2 (IGF2) genes. In a progression
      from population to functional studies, recent reports have shown that VNTR
      susceptibility alleles (class I) have different transcriptional effects on INS
      than protective VNTR alleles (class III) in thymus and pancreas, two tissues
      important in the pathogenesis of the disease. Similar VNTR transcriptional
      effects on IGF2 have also been proposed as a mechanism by which the IDDM2 locus
      confers susceptibility in addition to, or instead of, effects on INS. We
      evaluated this hypothesis by comparing IGF2 expression levels from chromosomes
      with the protective class III alleles to those with class I alleles in tissues
      relevant to type 1 diabetes pathogenesis. In thymus, class III alleles were
      associated with an IGF2 mRNA level of 4.7 +/- 0.9 (mean +/- SE, arbitrary units,
      n = 12) compared with 4.7 +/- 1.3 for class I alleles (n = 17). The same absence
      of a significant difference was found in pancreas, where class III alleles were
      associated with a level of 28.4 +/- 4.2 (n = 7) and class I alleles with a level
      of 29.5 +/- 5.2 (n = 6). There was a significant correlation between fetal age
      and IGF2 in both tissues, but fetal ages were not different in the genotype
      groups compared. We therefore did not detect any significant difference in IGF2
      mRNA levels associated with the protective class of VNTR alleles as compared with
      the predisposing class. This is evidence against the hypotheses that have
      suggested IGF2 is a mediator of IDDM2-encoded susceptibility and corroborates
      previous studies suggesting insulin is the gene involved.

PMID- 9588458
TI  - Molecular scanning of the insulin receptor substrate 1 gene in subjects with
      severe insulin resistance: detection and functional analysis of a naturally
      occurring mutation in a YMXM motif.

PMID- 9588459
TI  - Mutation screening of the human UCP 2 gene in normoglycemic and NIDDM morbidly
      obese patients: lack of association between new UCP 2 polymorphisms and obesity
      in French Caucasians.

PMID- 9588460
TI  - Insulin promoter factor 1 gene is not a major cause of maturity-onset diabetes of
      the young in French Caucasians.

PMID- 9588461
TI  - Mutations in the coding region of the insulin promoter factor 1 gene are not a
      common cause of maturity-onset diabetes of the young in Japanese subjects.

PMID- 9588462
TI  - Overexpression of placental leptin in diabetic pregnancy: a critical role for
      insulin.
AB  - Leptin, a small peptide produced by adipocytes, is implicated in an increasing
      number of endocrine regulations, including adiposity, satiety, puberty, and
      fertility. Although the factors involved in controlling maternal and fetal weight
      gain during pregnancy have not been fully elucidated, leptin has recently emerged
      as such a potential factor. In our study, we report the presence of high amounts
      of leptin mRNA and immunoreactive protein in the human placenta, establishing the
      placental synthesis of this hormone. A large (three- to fivefold) augmentation in
      leptin mRNA and protein was found in placentas from insulin-treated diabetic
      women. This finding was associated with increased concentrations of leptin and
      insulin in venous cord blood without modification of maternal circulating leptin
      levels. These data provide evidence that the placenta is a site for regulated
      leptin production in utero. Insulin is likely to play a critical role in this
      regulation, thus emphasizing the importance of placental leptin signaling in
      diabetic pregnancy.

PMID- 9588463
TI  - An association between NIDDM and a GAA trinucleotide repeat polymorphism in the
      X25/frataxin (Friedreich's ataxia) gene.
AB  - Friedreich's ataxia is the most common hereditary ataxia and is frequently
      associated with disturbances of glucose metabolism. This autosomal recessive
      disease is caused by the decreased expression of a mitochondrial protein,
      frataxin, encoded by the X25 gene. Homozygous expansion of a GAA repeat in the
      first intron of X25 inhibits frataxin expression and is associated with clinical
      disease. We evaluated whether heterozygous expansions of the triplet repeat in
      the frataxin gene X25 may be associated with NIDDM in two genetically distinct
      populations--one in Germany (n = 358) and the other in the U.S. (n = 292)--using
      a polymerase chain reaction-based assay. Intermediate expansions (10-36 repeats),
      which are longer than normal but not sufficient for the appearance of the ataxia
      phenotype, were found in 24.7 and 27.3% of these two NIDDM cohorts compared with
      7.6 and 6.3% of the matched control subjects (both P < 0.001). The odds ratios
      were 3.36 (95% CI 1.72-6.55) for the German group and 4.01 (2.08-7.74) for the
      U.S. group. Therefore, we conclude that the X25/frataxin GAA repeat polymorphism
      is associated with NIDDM in a frequency higher than any other mutation heretofore
      described. Further studies are needed to elucidate the possible role of frataxin
      in the pathogenesis of NIDDM.

PMID- 9588464
TI  - Laparoscopic anterior spinal arthrodesis with rhBMP-2 in a titanium interbody
      threaded cage.
AB  - Anterior lumbar interbody arthrodesis is commonly performed for conditions
      involving infection, deformity, and instability. The purpose of this
      investigation was to determine the effective dose of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) as a bone graft substitute inside a titanium
      threaded interbody fusion cage using a nonhuman primate model of laparoscopic
      anterior lumbar interbody arthrodesis. Eight adult rhesus monkeys underwent
      laparoscopic exposure of the lumbosacral spine followed by insertion of a hollow
      titanium threaded cylindrical cage (Sofamor-Danek, Memphis, TN, U.S.A.). Before
      insertion, the chamber of the cage was filled with a collagen sponge delivery
      vehicle soaked with either 0 mg/ml (sham, buffer only), 0.75 mg/ml (low dose), or
      1.5 mg/ml (high dose) of rhBMP-2 (Genetics Institute, Cambridge, MA, U.S.A.).
      Fusions were evaluated in a blinded fashion with plain radiographs and computed
      tomography (CT) scans 12 and 24 weeks after surgery, and by manual palpation and
      histology after euthanasia 24 weeks after surgery. All five monkeys treated with
      a cage filled with rhBMP-2 obtained a solid fusion as assessed by manual
      palpation. The two monkeys that received no growth factor did not achieve solid
      fusions. Plain radiographs were of limited value, with fusions best assessed on
      sagittally reconstructed CT scans. Scans from the two animals treated without
      growth factor showed ingrowth of bone only into the outer edges of the cage, but
      not through the center. Scans from the rhBMP-2-treated animals demonstrated
      arthrodesis with continuous bone growth through the cage. Histologic analysis
      demonstrated normal mature trabecular bone surrounding and growing through the
      cages, which correlated with the CT scan findings. We conclude that rhBMP-2
      delivered in a threaded titanium interbody cage can serve as a bone graft
      substitute in a nonhuman primate model. Sagittal reconstructed CT may be a better
      method to assess for fusion with this device.

PMID- 9588465
TI  - Guidelines to decortication in posterolateral spine fusion.
AB  - Despite the development of innovative approaches and the general success that has
      been achieved with spinal fusion, the rate of nonunion in some studies has been
      reported as high as 35%. Decortication has been shown to promote the fusion
      process and provides not only a rich source of vascular supply from the
      underlying cancellous bone, but also access to pluripotent stem cells within the
      marrow. Although the blood supply to the lumbar spine has been described, little
      attention has been paid to relevant areas of the spine most affected by
      decortication during the posterolateral fusion process. To assess these areas of
      the spine and attribute some potential importance to spinal fusion outcome, a
      perfusion study was designed to delineate the vascular anatomy involved in a
      decortication procedure. Cadaver spines were perfused with a radiopaque contrast
      material, fixed, decalcified, and cleared en bloc by the method of Spalteholz.
      Transverse, sagittal, and coronal slabs were made and the vascular supply was
      documented. The dominant intraosseous architecture of the vertebra reflected a
      cancellous bone structure, characterized by marrow and a sinusoidal blood
      distribution within a trabecular matrix. A contrasting architecture could be
      differentiated in the pars interarticularis that was more consistent with dense,
      cortical bone. Matrix from this region typified haversian lamellar bone and
      exhibited parallel osteons that contained a central vascular component. The
      relevance of this variance could have multiple implications, given the
      differences between cortical and cancellous bone in function, formation, healing,
      and remodeling. In posterolateral intertransverse process arthrodesis, the
      transverse processes and lateral facets are good areas to be decorticated,
      whereas the pars interarticularis is less attractive.

PMID- 9588466
TI  - Lumbar spinal stenosis: assessment of long-term outcome 12 years after operative
      and conservative treatment.
AB  - The present study focuses on the long-term prognosis of radiographically verified
      stenosis of the lower lumbar spine. The purpose here was to describe the outcome
      12 years after radiographic diagnosis of spinal stenosis and to identify factors
      predicting disability after operative or conservative treatment. Data were
      compiled on 75 patients (43 men and 32 women) with changes in functional
      myelography diagnostic for spinal stenosis. Their mean age at the interview 12
      years later was 61 years. The sagittal diameter of the dural sac was measured
      from baseline myelographs at all intervertebral levels and was corrected for
      magnification. In the interview, subjective outcome assessment was obtained with
      a structured questionnaire, and the low-back disorder was scored using the
      Oswestry disability index. The sagittal diameter of the dural sac was severely
      stenotic (<7.0 mm) in 32 patients (26 operated), and moderately stenotic (7.0
      10.5 mm) in 43 patients (31 operated). The severity of the stenosis significantly
      predicted disability, even when the effects of age, sex, therapy regimen, and
      body mass index were adjusted for. For moderate and severe stenosis, the adjusted
      mean Oswestry indices were 28.4 and 39.1, respectively (p = 0.01). Therapy as
      such (operative versus nonoperative) did not significantly correlate with later
      disability. The radiographic severity of lumbar spinal stenosis predicts
      disability independently of therapy regimen. Randomized clinical trials are
      needed to establish the indications for surgical and conservative treatment.
      Radiographic severity of the stenosis should be considered as an effect-modifying
      or confounding factor in clinical trials and other studies focusing on the
      outcome of lumbar spinal stenosis.

PMID- 9588467
TI  - Decompression in the surgical management of degenerative spondylolisthesis:
      advantages of a conservative approach in 290 patients.
AB  - The management of degenerative spondylolisthesis with laminectomy alone or
      laminectomy with fusion remains controversial. From the early 1970s to 1996, 290
      patients with degenerative spondylolisthesis were treated with 249 laminectomies
      and 41 fenestration procedures over an average of 3.2 levels. One level
      olisthesis was encountered in 250 patients, and two levels of slip in 40.
      Patients averaged 67 years of age, and were followed an average of 10 years.
      Using Prolo's outcome scale, 69% of patients exhibited excellent, 13% good, 12%
      fair, and 6% poor outcomes. Secondary decompressions with fusions for increased
      olisthy/instability (five patients) and recurrent stenosis/disc
      disease/instability (three patients) required one posterolateral "in situ" fusion
      and seven Texas Scottish Rite Hospital instrumented procedures. Decompression
      alone successfully managed degenerative spondylolisthesis in 290 patients treated
      over 3 decades, because only 8 (2.7%) required secondary fusion.

PMID- 9588468
TI  - Predisposing factors for infection in spine surgery: a survey of 850 spinal
      procedures.
AB  - A retrospective survey of 850 spinal procedures was conducted to determine risk
      factors for postoperative spinal infection. Some 574 posterior and 276 anterior
      procedures were evaluated. Infections were classed as early (within 19 weeks
      postoperatively) and late (> or = 20 weeks postoperatively), as well as deep and
      superficial infections. Previously postulated risk factors (i.e., diabetes,
      corticosteroid therapy, previous spinal surgery, obesity, chronic infection, and
      smoking) were investigated. Furthermore, it was hypothesized that three
      additional factors: extended preoperative hospitalization, prolonged operation
      duration, and high blood loss were risk factors not previously considered. A
      postoperative infection was evident in 22 of 850 procedures (19 early/three late
      infections, four superficial/18 deep infections). Most infections (n = 21)
      occurred with posterior instrumentation. Previously described factors were proven
      as risk factors. Extended preoperative hospitalization (p < 0.04), high blood
      loss (p < 0.01), and prolonged operation time (p < 0.001) were additionally
      determined as risk factors. The results suggest that routine prophylactic
      antibiotics might be unnecessary in anterior surgery, whereas extended
      prophylactics should be considered in posterior instrumentation, especially when
      risk factors are apparent.

PMID- 9588469
TI  - Intervertebral spacer as an adjunct to anterior lumbar fusion. Part I. Design,
      fabrication, and testing of three prototypes.
AB  - Failure of anterior lumbar fusions are common, because the bone graft is required
      to provide mechanical stability during creeping substitution and replacement with
      host bone. Support of the interspace with mesh, cages, plates, and rods results
      in an improved rate of fusion. The objective of this study was to develop an
      anterior interbody implant to stabilize adjacent vertebral segments during spinal
      fusion. Three prototypes of an intervertebral spacer for anterior lumbar
      stabilization were designed, fabricated, and tested in vitro. The implants were
      inserted vertically between adjacent vertebral bodies in fresh frozen cadaver
      swine and baboon spines after disc excision and vertebral body preparation. In
      vitro cyclic testing of the three prototypes implanted in porcine and baboon
      spines to 100,000 cycles showed no displacement of the implant at 560-N axial and
      16-Nm torsional loading. Three-point bending cyclic fatigue testing of the porous
      coated cylindrical implants (prototype 3) showed a maximum strength of 9,700 N in
      axial compressions. Analysis of the motion profiles at the site of implantation
      confirmed less axial displacement at the implant level compared with the
      uninstrumented levels above and below, but similar torsional displacements.
      Biomechanical testing of the three prototypes of anterior implants as well as
      radiographic, microstructural, and motion analysis confirmed implant stability
      and structural integrity in vitro. Based on these findings, implantation of a
      porous coated implant in baboons was undertaken as described in Part II (Nasca et
      al., this issue).

PMID- 9588470
TI  - Intervertebral spacer as an adjunct to anterior lumbar fusion. Part II. Six-month
      implantation in baboons.
AB  - Failure of interbody fusions in the lumbar spine are common due to reliance on
      the graft for structural support during healing by creeping substitution. Support
      of the interspace with an implant should result in improved fusion success. The
      objective of this study was to evaluate the stability of the implant in vivo and
      its potential as an adjunct to promote interbody arthrodesis. Prototype 3, a
      porous coated intervertebral spacer with extension lugs made of Ti-6A1-4V, was
      implanted vertically between adjacent lumbar vertebrae anteriorly in four baboons
      undergoing anterior interbody fusion. The animals were allowed freedom of
      activity for 6 months before being killed. A transperitoneal approach was made
      exposing the L4-L5 or L5-L6 interspace. At time of killing, clinical evaluation
      of the implant-vertebral body construct showed stability to manual stresses
      applied in extension, flexion, and rotation. Serial radiographs taken during the
      6 months of implantation showed no change in position or displacement of the
      implants. Axial and torsional cyclic loads were applied to each spine at 1
      cycle/s for 20,000 cycles. Statistical analysis of the motion profiles for intact
      and implanted spines demonstrated no significant difference in axial or
      rotational displacements at the arthrodesis level or adjacent unoperated levels,
      L1 and L4. The in vivo 6-month study in baboons confirmed implant stability and
      maintenance of disc space height. Variable osseous healing was noted. Release of
      plasma spray beading may have resulted from improper application on the implant
      or micromotion within the construct. A better method to mechanically interlock
      the plungers is being studied. Clinical trials based on this work appear
      justified.

PMID- 9588471
TI  - Neurocentral synchondrosis fracture in immature spines associated with pedicle
      screw type fixation devices.
AB  - The purpose of this study is to clarify the weak point in immature lumbar
      vertebrae associated with pedicle screw instrumentation. Ten immature thoracic
      and lumbar vertebrae were collected from calf spines. After installation of 6-
      and 7-mm-diameter pedicle screws into the pedicles of each specimen, pullout
      force was applied to the screw using the uniaxial MTS system until failure.
      Tightening torque during installation was measured. From the load-displacement
      curve, failure load was calculated and failure site was confirmed by radiographs.
      Inner pedicle diameters were measured after the pullout test, and percent fills
      of the pedicle screw were calculated. Mean tightening torque was 1.4 or 2.1 (Nm),
      mean failure load was 852.5 or 1,015.0 (N), and mean percent fill was 81.4 or
      93.5% for 6- or 7-mm screws, respectively. Tightening torque and percent fill in
      7-mm screws were significantly (p < 0.01) greater than that in 6-mm screws;
      however, failure load showed no significant difference (p = 0.10) between the two
      screw groups. Failure by screw pullout occurred at the screw-bone interface or
      through the neurocentral synchondrosis (NS). NS fractures were observed in 20% of
      6-mm screws, 60% of 7-mm screws, and 40% overall, whereas interface failures
      occurred in 80% of 6-mm screws, 40% of 7-mm screws, and 60% overall. In NS
      fracture group, tightening torque (p < 0.05) and percent fill (p < 0.01) were
      significantly greater than in the interface failure group. The results led us to
      conclude that the mechanism of the NS fracture is unclear. However, NS fracture
      could be one of the conceivable complications associated with pedicle screw
      fixation in the immature spine.

PMID- 9588472
TI  - Biomechanical study of lumbar spinal stability after osteoplastic laminectomy.
AB  - The biomechanical stability of the lumbar spine after two surgical procedures of
      total facetectomy and osteoplastic laminectomy was investigated using fresh
      frozen human cadaveric lumbar spine specimens. Six pure moments in flexion
      extension, right-left bending, and right-left twisting were applied and
      intervertebral motions were recorded using an optoelectronic motion measurement
      system. Neutral zone (NZ) and range of motion (ROM) under three conditions of
      intact, total facetectomy, and osteoplastic laminectomy were analyzed
      statistically to determine comparative biomechanical potential for instability.
      Results of NZ showed no changes in any direction with respect to the intact
      behavior after the two procedures. Also, in lateral bending, there were no
      significant increases in ROM after the two procedures. However, flexion-extension
      ROM increased significantly (+33%, p < 0.05) after the total facetectomy, but not
      after osteoplastic laminectomy. Axial rotation ROM increased remarkably after the
      total facetectomy (+113%, p < 0.05), but only moderately (+57%, p < 0.05) after
      the osteoplastic laminectomy. The osteoplastic laminectomy, which preserves the
      spinous process as well as the facet joints, maintains greater spinal stability
      than the total facetectomy.

PMID- 9588473
TI  - Transforaminal nerve root sleeve injection with corticosteroids, hyaluronidase,
      and local anesthetic in the failed back surgery syndrome.
AB  - Millions of patients with chronic sciatica are still treated with epidural
      corticosteroids. The efficacy of epidural corticosteroids remains questionable,
      especially in the chronic failed back surgery syndrome (CFBSS). The affected
      nerve root sleeve(s) are localized with the help of fluoroscopy and contrast dye.
      Local anesthetic diluted in 1,500 U hyaluronidase and 40 mg methylprednisolone is
      injected. Twenty patients with CFBSS, a small retrospective pilot study group,
      were treated. The success rate is evaluated using a verbal pain rating scale, 1
      month and 3 months after the last injection. Initially, 12 patients obtained very
      good pain relief, sustained for >3 months in 11 patients. In one patient, pain
      returned after >1 month. No complications were observed. This technique is
      worthwhile for patients with CFBSS and where epidural fibrosis is suspected to be
      the pain origin.

PMID- 9588474
TI  - Comparison of spinal mobility after Harrington and CD instrumentation.
AB  - Of 229 patients, 15 pairs of patients with right thoracic idiopathic scoliosis
      (King III) and 15 pairs with combined thoracic and lumbar scoliosis (King II)
      were identified. Each pair consisted of one patient with Harrington and the other
      with Cotrel-Dubousset instrumentation. Pairs were comparable with regard to
      thoracic curve magnitude, and level of end and stable vertebrae. Minimum follow
      up was 4 years postoperatively. Spinal mobility of patients in the coronal and
      sagittal plane, and axial rotation was measured with inclinometers. The
      differences between operatively treated groups are not significant. The more
      caudal instrumentation ends, the more reduced is spinal mobility in the coronal
      plane. Motion in operated patients is significantly reduced in comparison to a
      healthy reference group.

PMID- 9588475
TI  - Muscular and kinematic behavior of the lumbar spine during flexion-extension.
AB  - Reduction in lumbar muscular activity at full body flexion, known as flexion
      relaxation, has been studied in relation to overall trunk, lumbar spine, and hip
      flexion, but has not been evaluated in conjunction with motion on the segmental
      level. In this study, intervertebral motion in a lumbar motion segment, trunk
      flexion, and the electromyographic activity in the lumbar erector spinae muscles
      were simultaneously measured during dynamic flexion-extension in seven patients
      with chronic low back pain with symptoms suggesting segmental instability and in
      six asymptomatic controls. A linkage system, which attached directly to the
      spinous processes of a lumbar motion segment, was used to continuously measure
      the sagittal plane intervertebral motion, while a potentiometric goniometer
      measured trunk flexion; myoelectric activity was measured using surface
      electrodes. It was found that intervertebral motions, as well as trunk mobility,
      were significantly less in the patients, both in terms of range and pattern of
      motion. Flexion relaxation was demonstrated in the controls by a 78% decrease in
      myoelectric activity at full flexion, whereas in the patients, only a 13%
      reduction was found, with most of the patients experiencing no reduction at all.
      Flexion relaxation occurred only in subjects in whom intervertebral rotation had
      reached a stage of completion considerably before full trunk flexion was
      achieved. These findings suggest that persistent muscle activation, which
      restricts intervertebral motion, is a means by which the neuromuscular system
      provides stability to help protect diseased passive spinal structures from
      movements that may cause pain.

PMID- 9588476
TI  - Conservative treatment for cervical spondylotic myelopathy: achievement and
      sustainability of a level of "no disability".
AB  - We retrospectively reviewed 64 patients treated by the following methods:
      continuous head halter traction in bed (2 patients), cervical brace (19
      patients), plaster bed holding head and trunk (15 patients), and Crutchfield's
      skull traction (28 patients), using the Japanese Orthopaedic Association grading
      system of motor function. A rate of "no disability" was achieved in 27% in the
      upper and 26% in the lower extremities. The achieved function was maintained in
      most patients, and some improved further during the follow-up period (3-10
      years). The overall achievement rate was 34% in the upper and 28% in the lower
      extremities. Because the rate was significantly influenced by the degree of
      disability before treatment, the candidates are patients with mild disability for
      whom "no disability" is the goal.

PMID- 9588477
TI  - Evidence of plasticity in the pontocerebellar conditioned stimulus pathway during
      classical conditioning of the eyeblink response in the rabbit.
AB  - Electrical stimulation thresholds required to elicit eyeblinks with either
      pontine or cerebellar interpositus stimulation were measured before and after
      classical eyeblink conditioning with paired pontine stimulation (conditioned
      stimulus, CS) and corneal airpuff (unconditioned stimulus, US). Pontine
      stimulation thresholds dropped dramatically after training and returned to
      baseline levels following extinction, whereas interpositus thresholds and input
      output functions remained stable across training sessions. Learning rate,
      magnitude of threshold change, and electrode placements were correlated. Pontine
      projection patterns to the cerebellum were confirmed with retrograde labeling
      techniques. These results add to the body of literature suggesting that the pons
      relays CS information to the cerebellum and provide further evidence of synaptic
      plasticity in the cerebellar network.

PMID- 9588478
TI  - Asymmetric frontal brain activity, cortisol, and behavior associated with fearful
      temperament in rhesus monkeys.
AB  - The authors examined the hypothesis that rhesus monkeys with extreme right
      frontal electroencephalographic activity would have higher cortisol levels and
      would be more fearful compared with monkeys with extreme left frontal activity.
      The authors first showed that individual differences in asymmetric frontal
      electrical activity are a stable characteristic. Next, the authors demonstrated
      that relative right asymmetric frontal activity and cortisol levels are
      correlated in animals 1 year of age. Additionally, extreme right frontal animals
      had elevated cortisol concentrations and more intense defensive responses. At 3
      years of age, extreme right frontal animals continued to have elevated cortisol
      concentrations. These findings demonstrate important relations among extreme
      asymmetric frontal electrical activity, cortisol levels, and trait-like fear
      related behaviors in young rhesus monkeys.

PMID- 9588479
TI  - Differential involvement of the dorsal anterior cingulate and prelimbic
      infralimbic areas of the rodent prefrontal cortex in spatial working memory.
AB  - The present study examined the effects of quinolinic acid lesions of the dorsal
      anterior cingulate and prelimbic-infralimbic cortices on spatial working memory
      and spatial discrimination using go/no-go procedures. All testing occurred in a
      12-arm radial maze. In a working memory task, rats were allowed to enter 12 arms
      for a cereal reward. Three or 4 arms were presented for a 2nd time in a session,
      which did not result in a reward. In a spatial discrimination task, rats had
      successive access to 2 different arms. One arm always contained a reward, and the
      other never contained a reward. Prelimbic-infralimbic lesions impaired spatial
      working memory but only produced a transient spatial discrimination deficit.
      Dorsal anterior cingulate lesions did not induce a deficit in either task. These
      findings suggest that the prelimbic-infralimbic cortices, but not the anterior
      cingulate cortex, are important in spatial working memory.

PMID- 9588480
TI  - Perirhinal cortex contributions to performance in the Morris water maze.
AB  - Rats with bilateral, electrolytic lesions of perirhinal cortex (PRC), lateral
      entorhinal cortex (LEC), or combined lesions (PRLE) were impaired relative to
      controls (sham) during initial acquisition in the Morris water maze, although all
      groups were eventually able to learn to locate the platform. A further deficit in
      the performance of PRC and PRLE, but not LEC groups, was evident, however, when a
      probe trial was conducted 2 min (but not 24 hours) after training. When the
      performance of sham- and PRC-lesioned rats was tested with variable memory delays
      inserted between training and probe trials, lesioned rats displayed an increase
      in the rate of forgetting for information made available during the training
      trial. This finding suggests that the PRC normally stores information regarding
      the cue-platform relationship and transfers this information to related
      structures during water maze performance.

PMID- 9588481
TI  - Perplexing effects of hippocampal lesions on latent inhibition: a neural network
      solution.
AB  - Experimental data indicate that hippocampal lesions might impair, spare, or even
      facilitate latent inhibition (LI). Furthermore, when LI is impaired by the
      lesions, it might be reinstated by haloperidol administration. The present
      article applies a neural network model of classical conditioning (N. A. Schmajuk,
      Y. W. Lam, & J. A. Gray, 1996) to investigate the possible causes of these
      puzzling results. According to the model, LI is manifested because preexposure of
      the conditioned stimulus (CS) reduces Novelty, defined as proportional to the sum
      of the mismatches between predicted and observed events, thereby reducing
      attention to the CS and retarding conditioning. It is assumed that hippocampal
      lesions affect the prediction of events. Computer simulations reveal that,
      depending on the behavioral protocol (i.e., procedure and total time of CS
      preexposure), Novelty in hippocampal lesioned animals might be larger, equal, or
      smaller (corresponding to smaller, equal, or larger LI) than in normal controls.
      Reinstatement of LI by haloperidol administration is explained by assuming that
      dopaminergic antagonists decrease the value of Novelty, when Novelty increases
      following hippocampal lesions.

PMID- 9588482
TI  - Endogenous acetylcholine in the dorsal hippocampus reduces anxiety through
      actions on nicotinic and muscarinic1 receptors.
AB  - Dorsal hippocampal cholinergic modulation of behavior in different tests of
      anxiety was investigated by direct injection of the muscarinic M1 and M2 receptor
      antagonists, pirenzepine and gallamine, and the nicotinic receptor antagonist
      mecamylamine. In the social interaction test, the anxiogenic effect of
      pirenzepine (30-100 ng) provided evidence for a tonic cholinergic anxiolytic
      action mediated by postsynaptic M1 receptors. The anxiogenic action of
      mecamylamine (30 and 100 ng) was most likely mediated by its action of
      presynaptic nicotinic receptors to reduce acetylcholine release. Gallamine (10
      1,000 ng) was without effect, suggesting that M2 receptors in this brain region
      do not play a significant role in this behavioral test. On Trial 1 in the
      elevated plus-maze, the receptor antagonists were without any effect, but in
      those with a previous 5-min experience of the plus-maze pirenzepine and
      mecamylamine had anxiogenic effects in the dose range of 30-300 ng; gallamine
      (100 and 300 ng) was without significant effect.

PMID- 9588483
TI  - Neurocircuitry of conditioned inhibition of analgesia: effects of amygdala,
      dorsal raphe, ventral medullary, and spinal cord lesions on antianalgesia in the
      rat.
AB  - Pain inhibition (analgesia) is produced by learned danger signals and inhibited
      by learned safety signals (antianalgesia). Conditioned analgesia is mediated by
      brain-to-spinal pathways releasing spinal endogenous opiates. Spinal morphine
      mimics learned danger signals in producing analgesia, which is inhibited by
      antianalgesia. The circuitry mediating antianalgesia is unknown. These
      experiments demonstrate that raphe dorsalis, raphe magnus, and spinal
      dorsolateral funiculus lesions abolish antianalgesia. Other lesions had no effect
      on antianalgesia. More important, lesions that blocked development of conditioned
      analgesia did not block development of antianalgesia. Thus, neural circuitries
      mediating analgesia and antianalgesia were found to be distinct, and conditioned
      inhibition of analgesia was found to act by inhibiting the most distal part of
      the conditioned analgesia circuit, namely, the spinal cord.

PMID- 9588484
TI  - Does the bed nucleus of the stria terminalis mediate fear behaviors?
AB  - The bed nucleus of the stria terminalis (BNST) has been implicated in autonomic
      and hormonal reactions to fearful stimuli, but its role in behavioral reactions
      to these stressors is less clear. This is puzzling, because 2 closely related
      areas, the septum and the amygdala, have been repeatedly implicated in fear
      behaviors. To investigate further, the behavioral effects of BNST lesions were
      compared to those of septal and amygdaloid lesions in 2 models of rat anxiety:
      the plus-maze and shock-probe tests. Septal lesions inhibited rats' open-arm
      avoidance in the plus-maze and suppressed burying of the shock-probe, whereas
      amygdaloid lesions specifically inhibited shock-probe avoidance. However, BNST
      lesions produced none of these anti-fear effects; thus, its involvement in the
      behavioral expression of fear is questionable.

PMID- 9588486
TI  - Inhibition of adenosine deaminase by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA)
      mimics the effect of inescapable shock on escape learning in rats.
AB  - Three experiments examined the role of adenosine neuroregulation in the
      production of shuttle-escape deficits caused by prior exposure to inescapable
      electric shock in rats (learned helplessness). Intracerebroventricular
      administration of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), a selective
      adenosine deaminase inhibitor, mimicked the effect of earlier inescapable shock
      at a dose of 2.5 microM in previously restrained rats. Performance deficits
      produced by EHNA or by earlier exposure to inescapable shock were reversed by
      intraperitoneal injection of 10 mg/kg caffeine, an adenosine receptor antagonist.
      Finally, preexposure to an ineffective number of shocks interacted in synergy
      with an ineffective pretest dose (1.0 microM) of EHNA to maximize shuttle-escape
      latencies. These data implicate endogenous adenosine neuroregulation as a
      proximate mechanism in learned helplessness and conservation-withdrawal.

PMID- 9588485
TI  - Light deprivation accelerates recovery from frontal cortical neglect: relation to
      locomotion and striatal Fos expression.
AB  - Rats given unilateral medial agranular (AGm) cortex ablations show neglect for
      contralateral multimodal stimuli, symptoms that are reversed by 48 hr of light
      deprivation. To address processes that contribute to this restorative effect,
      both the rats' locomotion and basal ganglia c-fos expression were studied. AGm
      lesioned rats showed less activity in continuous darkness than in normal (12 hr
      light/12 hr dark) cycles, and the reduced locomotion correlated with the extent
      of their subsequent behavioral recovery. The AGm ablation reduced the numbers of
      amphetamine-stimulated Fos-immunoreactive nuclei in the ipsilateral dorsolateral
      striatum, where the AGm innervation is normally densest. Light deprivation also
      reduced Fos in this striatal region and attenuated the lesion-induced hemispheric
      Fos asymmetry. A restored balance of activity between the 2 hemispheres,
      especially the basal ganglia, appears central to the action of light deprivation.

PMID- 9588487
TI  - Alterations in the reinforcing efficacy of cocaine in adult rats following
      prenatal exposure to cocaine.
AB  - Adult male rats gestationally exposed to cocaine and nonexposed control offspring
      were examined for differences in operant responding for cocaine and sucrose
      reinforcement. Offspring were derived from dams that had received subcutaneous
      injections of 40 mg/kg/3cc cocaine hydrochloride daily on gestational Days 8-20
      and nontreated control dams. Although no prenatal treatment differences were seen
      when the animals lever pressed for sucrose pellets on a progressive-ratio (PR)
      schedule, adult offspring prenatally exposed to cocaine were observed to exhibit
      an enhanced rate of cocaine intravenous self-administration on a fixed-ratio 5
      (FR-5) schedule along with a marked decrease in break point on the PR
      reinforcement schedule. These results suggest that the reinforcing efficacy of
      cocaine may be reduced in animals with a prenatal history of cocaine exposure.

PMID- 9588488
TI  - Prenatal cocaine alters social competition of infant, adolescent, and adult rats.
AB  - This series of experiments examined whether gestational cocaine exposure alters
      later social behavior exhibited during competition for biologically relevant
      stimuli. Rat offspring were derived from dams that received subcutaneous
      injections of 40 mg/kg/3cc cocaine HCl daily on gestational Days 8-20, pair-fed
      dams injected with saline, or nontreated control dams. Offspring competed with
      peers for access to a nipple in infancy, and to water in adolescence or
      adulthood. Prenatal cocaine exposure resulted in a decreased ability of cocaine
      exposed infant rats to compete successfully for a nipple. Although adolescent and
      adult cocaine-exposed rats were no less successful than controls when competing
      for water, they exhibited a notable increase in aggression toward competitors
      during testing. Data provide evidence of alterations in social behavior and
      social competition as a result of prenatal cocaine exposure.

PMID- 9588489
TI  - Kainic acid lesions of the superior olivary complex: effects on sound
      localization by the albino rat.
AB  - The ability of rats to localize sounds in space was determined before and after
      kainic acid lesions of the superior olivary complex (SOC). Animals were tested
      with a 45-ms noise burst delivered from loudspeakers on the right or left of
      midline. Anatomical data showed that the lesions destroyed neurons in SOC while
      preserving fibers of passage in the trapezoid body and other decussating pathways
      of the auditory brainstem. Animals with either unilateral or bilateral SOC
      lesions were impaired in their ability to localize a single noise burst
      postoperatively. Deficits were also found after unilateral lesions restricted
      primarily to the lateral superior olive. SOC lesions resulted in an elevation in
      minimum audible angles for sound localization.

PMID- 9588490
TI  - Effects of benzodiazepine receptor ligands on the ingestion of sucrose,
      intralipid, and maltodextrin: an investigation using a microstructural analysis
      of licking behavior in a brief contact test.
AB  - Microstructural analysis of licking behavior in the rat was conducted (a) to
      describe in detail the characteristics of benzodiazepine-induced changes in
      ingestion and (b) to determine if the changes are consistent with an alteration
      in palatability. The effects of the benzodiazepine receptor (BZR) agonist
      midazolam (0.3-3 mg/kg), and the partial inverse agonist Ro 15-4513 (0.3-3
      mg/kg), on licking for several concentrations of sucrose, Intralipid, and
      maltodextrin in a brief contact test were investigated. Midazolam increased the
      total number of licks for all 3 fluids; conversely, Ro 15-4513 decreased the
      total number of licks. Midazolam increased mean bout duration for sucrose and
      maltodextrin drinking and there was a trend toward a similar effect with
      Intralipid drinking. Ro 15-4513 reduced mean bout duration for all 3 test fluids.
      These data are discussed in terms of bidirectional changes in fluid palatability
      by drug actions at BZRs.

PMID- 9588491
TI  - Treatment of patients with toxic multinodular goiter.
AB  - The medical records of 253 patients evaluated for toxic multinodular goiter from
      1975 through 1993 were reviewed to determine treatment trends, success, and
      complications. Of the 235 (93%) treated, 174 (74%) received surgical treatment
      and 61 (26%) received radioiodine (131I) treatment. Three months after initial
      treatment, 82% of surgically treated patients became euthyroid or hypothyroid
      compared with 21% of the 131I group. Among the 131I-treated patients, 20%
      required a second treatment, whereas none needed further treatment in the
      surgical group. At 2 years, the estimated probability of success was similar. The
      probability of post-treatment hypothyroidism was significantly higher for
      surgically treated patients, which is expected.

PMID- 9588492
TI  - Ultrasound-guided fine-needle aspiration biopsy of thyroid masses.
AB  - The purpose of this study was to determine the impact of ultrasound-guided fine
      needle aspiration biopsy (USFNA) in the cytological diagnosis of nodular thyroid
      disease. It remains unclear exactly what role USFNA should play in the
      cytological diagnosis of nodular thyroid disease. All patients who underwent fine
      needle aspiration (FNA) for nodular thyroid disease at Stanford University
      Medical Center from 1991 to 1996 were included in the study. Histopathologic
      diagnoses were compared to cytological diagnoses for those patients who underwent
      surgery. FNA was performed on a total of 497 thyroid nodules. Palpation-guided
      FNA (pFNA) was performed on 370 nodules, and USFNA was done on 127. The USFNAs
      were performed for the following reasons: 95 (75%) for nonpalpable or difficult
      to-palpate nodules; 14 (11%) for previously failed FNA; and 18 (14%) for
      incidentally detected nodules. FNA had an unsuccessful biopsy rate of 16% and a
      sensitivity and specificity of 89% and 69%, respectively. USFNA had an
      unsuccessful biopsy rate of 7% and a sensitivity and specificity of 100% and
      100%, respectively. The cancer yield at surgery for pFNA was 40%, and the cancer
      yield at surgery for USFNA was 59%. The complementary use of USFNA with pFNA
      improves the diagnostic approach to nodular thyroid disease. The use of USFNA has
      increased the cancer yield at surgery and the sensitivity of thyroid biopsy at
      our institution.

PMID- 9588493
TI  - Evidence for the segregation of three different mutated alleles of the
      thyroglobulin gene in a Brazilian family with congenital goiter and
      hypothyroidism.
AB  - We have previously reported a Brazilian family with congenital goiter,
      hypothyroidism, and marked impairment of thyroglobulin (Tg) synthesis. Analysis
      of the Tg mRNA in the goiter of one of the siblings revealed a cytosine to
      thymine transition creating a stop codon at position 1510. This point mutation is
      removed from the majority of Tg mRNA transcripts by the preferential generation
      in the goiter of a 171 nt deleted Tg mRNA by alternative splicing. The nonsense
      mutation destroys a TaqI site at this position in the mutant Tg gene. Using
      polymerase chain reaction (PCR) amplification and TaqI digestion we found that
      two siblings affected with goiter and hypothyroidism, as well as the father and
      three siblings with normal thyroid function, are all heterozygous for the
      nonsense mutation. This implies that an additional mutation must be present in
      the affected individuals, generating a compound heterozygote genotype. A new
      polymorphism within the thyroglobulin gene represented by three alleles has been
      detected. This was documented by the TaqI restriction enzyme and phTgM3 probe
      hybridization that showed a three allelic polymorphism with fragment sizes of
      16.5 kb (allele A), 14.5 kb (allele B) and 11.0 kb (allele C). Segregation
      analysis of these alleles in the family indicated that the two affected siblings
      were homozygous for the allele C. In contrast the unaffected father and three
      other siblings, who carried the nonsense mutation, were heterozygous for alleles
      B and C. Analysis of the Tg genotypes implies that two additional mutations of
      the Tg gene must segregate in this family to account for the observed phenotypes.

PMID- 9588495
TI  - Analysis of the promoter of the thyrotropin receptor gene and the entire genomic
      sequence of thyroid transcription factor-1 in familial congenital hypothyroidism
      due to thyrotropin unresponsiveness.
AB  - We previously reported that our patients with congenital primary hypothyroidism
      associated with thyrotropin (TSH) unresponsiveness through an autosomal recessive
      pattern of inheritance did not have mutations in the coding region of the TSH
      receptor gene. In the current study, we analyzed the promoter of the TSH receptor
      gene and the entire region of the thyroid transcription factor-1 (TTF-1) gene,
      including promoter, two exons, and one intron, because expression of the rat TSH
      receptor gene is reported to be stimulated by the interaction of the promoter of
      the TSH receptor gene with TTF-1. Screening for mutations was performed by RNase
      cleavage assay, and the polymerase chain reaction (PCR) products were
      subsequently sequenced by the automatic sequencer. In the promoter of the TSH
      receptor gene, a duplication of nucleotides -346 to -330 was detected in one
      allele, but haplotype analysis of the family demonstrated lack of linkage between
      the duplication and the TSH unresponsiveness. The same duplication was also
      observed in some normal subjects. In the TTF-1 gene, we detected a transition
      (guanine to adenine) in the intron at the minus four position of cryptic 3'
      splice site in one allele, but absence of linkage suggested that the transition
      was not responsible for the TSH unresponsiveness. The same transition also was
      found in some normal subjects. These results suggest that TSH unresponsiveness in
      our patients is unlikely to be caused by mutations either in the promoter of the
      TSH receptor gene or in the TTF-1 gene.

PMID- 9588494
TI  - Description of a Brazilian patient bearing the R271W Pit-1 gene mutation.
AB  - The pituitary-specific transcription factor Pit-1/GHF-1 is responsible for
      pituitary development and expression of somatotrophs and lactotrophs as well as
      hormonal regulation of the prolactin (PRL) and thyrotropin (TSH) beta genes by
      thyrotropin-releasing hormone (TRH) and cyclic adenosine monophosphate (cAMP).
      Pit-1 gene mutations result in complete growth hormone (GH) and PRL deficiencies
      and variable degrees of TSH deficiency, producing the clinical syndrome of
      combined pituitary hormone deficiency (CPHD). Several cases of mutations in the
      Pit-1 gene have been reported; the most common one is a sporadic mutation
      altering an arginine (R) to a tryptophan (W) in codon 271, in one allele of the
      Pit-1 gene. We describe a case of a 38-year-old woman, born to consanguineous
      parents, presenting with growth failure and hypothyroidism. Growth failure was
      noted from early infancy, whereas hypothyroidism was only apparent from
      adolescence. She had almost undetectable GH and PRL levels and an inappropriate
      low TSH for very low triiodothyronine (T3) and thyroxine (T4) levels, while the
      remaining pituitary evaluation was normal. The pituitary gland was hypoplastic by
      magnetic resonance imaging. A point mutation in exon 6, monoallelic, causing a C
      to T substitution that changes amino acid 271 from Arg (R) to Trp (W) was
      identified. Children with Pit 1 mutations and delayed onset of hypothyroidism may
      be initially diagnosed as isolated GH deficiency.

PMID- 9588496
TI  - Possible involvement of Fas-mediated apoptosis in eye muscle tissue from patients
      with thyroid-associated ophthalmopathy.
AB  - In order to investigate the possible involvement of apoptosis in the pathogenesis
      of thyroid-associated ophthalmopathy (TAO), we studied the expression of Fas, Fas
      ligand (FasL), and Bcl-2 in extraocular muscle tissues from patients with TAO by
      immunohistochemistry using monoclonal antibodies against Fas, FasL, and Bcl-2.
      Apoptosis was detected by in situ end-labeling of fragmented DNA. Apoptosis was
      detected in extraocular muscle tissues from 17 of 19 patients with TAO and, to a
      smaller degree in 4 of 7 normal control subjects. The mean percentages of
      apoptotic nuclei were 12.1% in TAO eye muscle fibers and 16.4% in TAO
      interstitial cells, compared with 2.2% and 0.4% in normal eye muscle fibers and
      interstitial cells, respectively. The percentage of apoptotic nuclei in eye
      muscle fibers correlated with the enlargement of eye muscle tissue (r = 0.47, p <
      0.05). Fas was demonstrated on the surfaces of extraocular muscle fibers in 11 of
      18 patients with TAO, but not in normal extraocular muscle tissues. Neither TAO
      nor normal extraocular muscle tissues expressed Bcl-2. FasL was detected in
      infiltrating mononuclear cells in extraocular muscle tissue from a patient with
      TAO. These data suggest that Fas-mediated apoptosis may occur in extraocular
      muscle tissue from patients with TAO and may be involved in the late stage of
      TAO.

PMID- 9588497
TI  - Increase of thyroid stimulating activity in Graves' immunoglobulin-G by high
      polyethylene glycol concentrations using porcine thyroid cell assay.
AB  - Cyclic adenosine monophosphate (cAMP) production during a 5-hour incubation using
      porcine thyroid cells (PTC) was stimulated significantly more by polyethylene
      glycol (PEG) 22.5% precipitated fractions (ppt frs) than by PEG 12.5% ppt frs
      from almost all Graves' sera. However, the thyrotropin (TSH) binding inhibition
      (TBI) activities of the PEG 12.5% and 22.5% ppt frs using porcine thyroid
      membranes were similar, and did not change in the 5-hour incubation. When the PEG
      12.5% ppt fr from Graves' serum and the PEG 22.5% ppt fr from normal human serum
      (NHS) were coincubated, cAMP production was also stimulated as much as by the PEG
      22.5% ppt fr from Graves' serum. When purified thyroid stimulating antibody
      (TSAb)-immunoglobulin G (IgG) and the PEG 22.5% ppt fr from NHS were coincubated,
      increased cAMP production was also observed, whereas bovine thyrotropin (bTSH)
      did not produce this effect. When purified TSAb-IgG and PEG solutions were
      coincubated, maximum increases in cAMP production (approximately 10-fold) with 5%
      PEG were found, whereas no increase was observed using bTSH. The stimulatory
      effect of high PEG concentrations on thyroid stimulating activity was observed by
      TSAb-IgG in salt-free or salt-containing medium (<0.15 mol/L NaCl concentration)
      but not by either TSAb-IgG conjugated to protein A-sepharose 4B or the
      inactivated TSAb-IgG by the treatment of 70 degrees C for 10 minutes. No
      stimulatory action by PEG was found with the thyroid stimulating substances such
      as GTPgammaS, forskolin, or pituitary adenylate-cyclase activating polypeptide
      (PACAP). The increased thyroid stimulating activity of Graves (IgG) at high PEG
      concentrations suggests the existence of some factors influencing the ability of
      TSAb to stimulate thyroid cells, although the exact mechanism remains to be
      clarified.

PMID- 9588498
TI  - Solitary cerebellar metastasis from papillary thyroid carcinoma: a case report.
AB  - Papillary thyroid carcinoma is a common thyroid malignancy that generally has a
      good prognosis. However, this type of cancer may give rise to distant metastasis
      and may behave more aggressively in older patients. Here we report clinical,
      radiological, and pathological findings of a patient with papillary thyroid
      carcinoma who had a solitary cerebellar metastasis. The patient was known to have
      metastatic thyroid cancer to the lungs, but this had been stable and the
      cerebellar metastasis presented an unanticipated significant problem. The rapid
      detection of cerebellar metastatic disease is critical because neurosurgical
      removal of the solitary lesion should be considered as the treatment of choice.
      This case also serves to remind us of the importance of considering possible
      metastatic brain lesions and their acute life-threatening complications in
      contrast to the relatively prolonged course associated with metastases of thyroid
      carcinoma to other organs.

PMID- 9588499
TI  - Simultaneous involvement of thyroid by Riedel's [correction of Reidel's] disease
      and fibrosing Hashimoto's thyroiditis: a case report.
AB  - We report an unusual thyroid lesion showing histologic features of both Riedel's
      [corrected] disease and fibrosing Hashimoto's thyroiditis in a 57-year-old white
      female. The clinical presentation was hypothyroidism associated with a solitary
      firm to hard cold nodule replacing the entire right lobe of thyroid gland.
      Pathological examination demonstrated extensive replacement of the thyroid
      parenchyma with dense keloidal fibrosis, intermixed well-developed lymphoid
      follicles, scattered lymphocytes, and plasma cells. The fibrotic process extended
      into the perithyroidal soft tissues and skeletal muscle with complete
      obliteration of the thyroid capsule. These findings were consistent with Riedel's
      [corrected] disease. However, the immunohistochemical stains for B and T markers
      and immunoglobulin light chains showed an immunoprofile consistent with
      Hashimoto's thyroiditis. This combination of Riedel's [corrected] disease and
      fibrosing Hashimoto's thyroiditis is rare and coincidental, as both represent two
      distinct clinicopathological entities.

PMID- 9588500
TI  - Ligand- and nuclear factor-dependent change in hydrophobicity of thyroid hormone
      beta1 receptor.
AB  - An aqueous two-phase partitioning assay was performed using in vitro translated
      human thyroid hormone beta1 receptor (TRbeta1). Wild-type TRbeta1 was less
      hydrophobic in the presence of both triiodothyronine (T3) and nuclear extract.
      This reflects a conformational change, or change in electrostatic properties, of
      the TRbeta1-nuclear factor complex as a result of T3 binding. Mutant TRbeta1s
      with reduced T3 binding affinity required a higher concentration of T3 for the
      shift of hydrophobicity, and a mutant without T3 binding activity did not show
      any shift, even in the presence of 1 mM T3. The unique mutant receptor, R243Q,
      has impaired transcriptional function despite virtually normal binding affinity
      for T3. When this mutant was examined in this assay, the shift of hydrophobicity
      was significantly impaired even in the presence of both nuclear extract and a
      high concentration of T3. Nuclear extract of COS1 cells did not affect the T3
      binding affinity of R243Q. These results indicate that the R243Q mutant has
      impaired a ligand-dependent conformational change and interaction with nuclear
      factor(s). Inability of R243Q to interact normally with nuclear factor(s) may
      explain, in part, the molecular mechanism of discordance between ligand binding
      and transactivation function of this mutant.

PMID- 9588501
TI  - Effects of thyroid hormone on catecholamine and its metabolite concentrations in
      rat cardiac muscle and cerebral cortex.
AB  - Clinical and experimental data suggest that thyroid hormone affects the actions
      of catecholamine (CA). However, the serum or tissue levels of CA during thyroid
      disorders have not been well defined. Accordingly, we investigated the levels of
      CA and their metabolites in the cardiac muscle, the cerebral cortex, and the
      plasma of rats with hyperthyroidism and hypothyroidism versus euthyroid animals.
      The Neurochem analyzer system (ESA, Inc., Bedford, MA) was used in such
      determinations. The cardiac muscles of hyperthyroid rats exhibited a 16% decrease
      in the levels of 1-dopa, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) as
      compared with those in euthyroid rats. The levels of norepinephrine (NE) in
      cardiac muscle of these rats increased significantly (5.2-fold) relative to the
      levels in euthyroid rats. NE was undetectable in the cardiac muscles of the
      hypothyroid rats. Epinephrine (E) and dopamine (DA) were not detected in the
      cardiac muscles of the rats with either thyroid disorder. Levels of E and 3,4
      dihydroxymandelic acid (DOPEG) were detected only in the cerebral cortex of
      hyperthyroid rats. The cerebral cortex levels of 3-methyoxytyramine (3-MT), 3,4
      dihydroxyphenylacetic acid (DOPAC), metanephrine (MN), and homovanillic acid
      (HVA) were all significantly increased in the hyperthyroid versus the euthyroid
      rats. The cerebral cortex levels of DA, NE, normetanephrine (NMN), and VMA in the
      hyperthyroid rats all showed a significant decrease. Levels of NE, NMN, and DOPAC
      in the cerebral cortex increased significantly in the hypothyroid rats. The level
      of VMA was undetectable in cerebral cortex of such animals. Data from studies on
      cardiac muscle and cerebral cortex indicate that the changes in CA and CA
      metabolites are responsible in part for the cardiovascular and the central
      nervous system symptoms observed in hyperthyroidism and hypothyroidism.

PMID- 9588503
TI  - A different field.

PMID- 9588502
TI  - Neurilemmoma of the neck.

PMID- 9588504
TI  - Management of upper extremity central venous obstruction using interventional
      radiology.
AB  - Upper extremity central vein stenosis/occlusion is responsible for significant
      morbidity. The objective of this report is to review our management using
      interventional radiological techniques and to determine the long-term clinical
      results. All radiological interventions for central vein stenosis/occlusion (n =
      59) between July 1991 and July 1996 at our institution were reviewed. The
      interventions consisted of thrombolytic therapy alone in 10 cases, PTA in 40
      cases (combined with initial thrombolytic therapy in 6 cases), and deployment of
      a venous stent in 9 cases. At follow-up, the cumulative success (patency and
      relief of symptoms) was determined (Kaplan-Meier method). The involved vein was
      the subclavian, axillary, or innominate (SUB-AX-INN) in 45 cases and the superior
      vena cava (SVC) in 14 cases. The etiology was secondary to an indwelling foreign
      body (catheter, pacemaker lead) in 53 cases (90%), and spontaneous in only 6
      cases (10%). The average follow-up after intervention was 17.2 months, with a
      cumulative success of 70 +/- 7.5% at 2 years, with rapid decline thereafter.
      Analysis of the failure quantiles revealed that 25% failed by 17 months, 50%
      failed by 26.6 months, and 75% failed by 33.8 months. There were no subgroup
      differences (log-rank test) for stenosis versus occlusion (p = 0.526), SUB-AX-INN
      versus SVC (p = 0.744), or if the intervention was begun < 5 days versus > or =5
      days after symptom onset (p = 0.240), or whether or not a stent was deployed (p =
      0.893). Interventional radiological techniques should be considered when symptoms
      from upper extremity central vein stenosis/occlusion are severe and disabling, or
      when veno-access or maintenance of patency of an ipsilateral arteriovenous (A-V)
      access is necessary. These results suggest an acceptable short-to medium-term
      solution.

PMID- 9588505
TI  - Early flow surface endothelialization before microvessel ingrowth in accelerated
      graft healing, with BrdU identification of cellular proliferation.
AB  - The purpose of this report was to determine if flow surface endothelialization
      could precede microvessel ingrowth from the perigraft area in porous Dacron
      grafts, by using an accelerated graft healing model with short implant periods.
      Dacron grafts were implanted in the abdominal aorta of 22 dogs and wrapped in
      autogenous inferior vena cava (IVC), which provided excellent conditions for
      extramural angiogenesis, microvessel development, and ingrowth toward the graft.
      Retrieval times were 7 days (n = 4), 8 days (n = 5), 9 days (n = 4), 10 days (n =
      3), 11 days (n = 4) and 12 days (n = 3) postoperatively. Graft surfaces were
      evaluated for thrombus coverage, cell coverage, and the number of micro-ostia.
      Components and cellular types in the graft wall and on the surface were studied
      and characterized with H&E, histochemical, and immunocytochemical staining. BrdU
      labeling was also used, to identify the areas where cells were actively
      proliferating. All grafts were patent. Although the degree of IVC/graft
      attachment varied, isolated islands of endothelial-like cells were found at the
      midgraft areas at each time period, and immunocytochemically confirmed as
      endothelial cells. There were two healing patterns: (1) surface
      endothelialization before microvessel/tissue ingrowth from the perigraft areas,
      and (2) surface endothelialization with full wall microvessel and tissue
      presence. Surface endothelialization was observed before perigraft tissue
      ingrowth, indicating that fallout healing is an independent source of
      endothelialization for porous grafts.

PMID- 9588506
TI  - Dexamethasone and enalapril suppress intimal hyperplasia individually but have no
      synergistic effect.
AB  - Vascular injury is associated with complex interactions that lead to development
      of intimal hyperplasia (IH). We have demonstrated previously that the
      corticosteroid dexamethasone and the ACE-inhibitor enalapril are effective in
      suppressing the development of IH. We hypothesize that due to distinctly
      different pharmacologic mechanisms of action, a synergistic effect would be
      expected if these agents were given in combination. Forty New Zealand White
      rabbits underwent balloon catheter denudation of the carotid artery. Animals were
      divided into four equal treatment groups and received daily intramuscular
      injections: Group 1, saline; Group 2, enalapril 0.07 mg/kg, Group 3,
      dexamethasone 0.125 mg/kg; and Group 4, enalapril 0.07 mg/kg plus dexamethasone
      0.125 mg/kg. Vessels were harvested at 12 weeks and intimal hyperplasia was
      measured as a ratio of the absolute area of IH to the normalized area enclosed by
      the internal elastic lamina (IH/IEL). Mean values for IH/IEL are expressed as a
      percent (SD): Group 1, 32.31 (14.9); Group 2, 9.47 (2.11); Group 3, 5.40 (4.14);
      and Group 4, 8.49 (4.27). All treatment groups demonstrated significant
      suppression of IH compared to the control group (p < 0.01); dexamethasone was
      more effective than enalapril (p = 0.01). There was no statistical difference in
      IH suppression between respective agents and the combination group (p > 0.10).
      Coadministration of dexamethasone and enalapril provides no advantage over single
      agent therapy in suppressing the development of IH, suggesting that maximal
      suppression is obtained with single-agent treatment or that these agents affect
      IH through a common pathway.

PMID- 9588507
TI  - Expression of matrix metalloproteinases and TIMPs in human abdominal aortic
      aneurysms.
AB  - Degradation of extracellular matrix, especially elastin, within the aortic wall
      is a hallmark of abdominal aortic aneurysms (AAAs). Normal turnover of matrix
      proteins is mediated by a family of enzymes called matrix metalloproteinases
      (MMPs). MMP activity is regulated by proteins called tissue inhibitors of
      metalloproteinases (TIMPs). We analyzed the expression of all known MMPs with
      established elastolytic activity and TIMPs in human AAA and control tissue. mRNA
      coding for MMP-9, MMP-2, human macrophage metalloelastase, MMP-7, TIMP-1, and
      TIMP-2 were amplified by reverse transcriptase-PCR in control and AAA tissue. A
      Northern blot assay was used to measure the levels of mRNA coding for MMP-2, MMP
      9, TIMP-1, and TIMP-2. Control aortic tissue was obtained from patients with
      occlusive disease and from organ donors. The expression of MMP-7 and human
      macrophage metalloelastase was not detected in any aortic specimens. By Northern
      blot analysis the mean level of MMP-2 mRNA was not significantly different
      between control groups and AAAs (normalized values: occlusive, 1.5 +/- 0.8, n =
      3; donor, 4.5 +/- 2.2, n = 6; AAA, 4.0 +/- 0.95, n = 15). There was a significant
      increase in the level of MMP-9 mRNA in AAA specimens (occlusive, 16.8 +/- 3, n =
      3; donor, 5.7 +/- 1.2, n = 6; AAA, 56.7 +/- 11, n = 15, p = 0.0069). The levels
      of mRNA coding for TIMP-1 were not significantly different. There was a small but
      statistically significant increase in TIMP-2 mRNA in AAA tissue. These data
      support the hypothesis that increased activity of MMP-9, but not MMP-2, is an
      important factor in the etiology of AAAs. This enhanced MMP-9 activity could then
      result in degradation of the ECM, leading to aneurysmal dilatation.

PMID- 9588508
TI  - Carotid resection and replacement with autogenous arterial graft during operation
      for neck malignancy.
AB  - Carotid artery resection as part of the management of advanced head and neck
      cancers remains controversial. Since 1991, 30 patients have undergone resection
      of the carotid artery with immediate reconstruction using superficial femoral
      artery as replacement conduit. There was one stroke/death. Forty-three percent
      developed neck wound problems but no grafts failed or hemorrhaged. Mean follow-up
      was 20 months (3-76) and mean life expectancy was 16 months from the time of
      surgery. Fifty-eight percent were free of local recurrence at the time of death.
      There was a 35% disease-free survival rate at 2 years. These results compare
      favorably with alternative therapy including carotid ligation or shaving tumor
      from the carotid artery. Given the importance of cerebral perfusion and local
      tumor control we offer superficial femoral artery as a durable conduit for
      immediate extracranial carotid reconstruction in the often hostile environment
      associated with cancer resection in the neck.

PMID- 9588509
TI  - Determination of 60% or greater carotid stenosis: a prospective comparison of
      magnetic resonance angiography and duplex ultrasound with conventional
      angiography.
AB  - The morbidity and cost of conventional angiography (CA) have focused recent
      efforts in cerebrovascular imaging upon the exclusive use of noninvasive
      techniques. Our purpose was to prospectively evaluate carotid magnetic resonance
      angiography (MRA) and to compare its accuracy with color-flow duplex (CFD). Fifty
      patients were prospectively evaluated with CA and MRA after clinical and CFD
      findings indicated the need for carotid angiography. CFD measurements of peak
      systolic velocity (PSV) and end-diastolic velocity (EDV) were made. MRA results
      were categorized as 0%-39%, 40%-59%, 60%-79%, or 80%-99% stenosis or occluded.
      Determination of percent carotid stenosis by CA was made as in the North American
      Symptomatic Carotid Endarterectomy Trial (NASCET). Using receiver operating
      characteristic (ROC) curves, the probability of correctly predicting a > or =60%
      stenosis using various CFD thresholds and MRA was assessed. Sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      in determining > or =60% stenosis were estimated. For MRA the sensitivity was 85%
      (95% Confidence Interval [CI] = 69%-94%), specificity 70% (CI = 56%-81 %), PPV
      68% (CI = 53%-80%), and NPV 86% (CI = 72%-94%). For CFD the sensitivity was 89%
      (CI = 74%-96%), specificity 93% (CI = 82%-98%), PPV 89% (CI = 74%-96%), and NPV
      93% (CI = 82%-98%). When MRA and CFD results were concordant (n = 64), the
      sensitivity was 100% (CI = 89%-100%), specificity 95% (CI = 81%-99%), PPV 94% (CI
      = 77%-99%), and the NPV was 100% (CI = 92%-100%). The area under the ROC curve
      for CFD was 95%, compared to 83% for MRA (p = 0.0005). We conclude that the low
      specificity of MRA precludes its use as the definitive imaging modality for
      carotid stenosis. The 93% specificity of CFD alone warrants its consideration as
      a definitive carotid imaging study. By ROC curve analysis, CFD offers superior
      accuracy to MRA. Our data support noninvasive preoperative carotid imaging for
      detecting a threshold stenosis of > or =60% whether CFD is used alone, or in
      combination with the selective use of MRA.

PMID- 9588510
TI  - Predictive ability of duplex ultrasonography for internal carotid artery stenosis
      of 70%-99%: a comparative study.
AB  - This study prospectively compared the accuracy of published duplex
      ultrasonographic criteria for 70%-99% internal carotid artery (ICA) stenosis
      according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET)
      method to determine angiographic stenosis. From March 1, 1995 to December 1,
      1995, all patients considered for carotid endarterectomy (CEA) were studied with
      carotid duplex ultrasound and carotid angiography within 1 month of the
      ultrasound study. Duplex measurements of ICA peak systolic velocity (PSV), end
      diastolic velocity (EDV), and ratio of the ICA to common carotid artery (CCA)
      PSVs were recorded. Degree of stenosis on angiography was determined using NASCET
      criteria. A MEDLINE search to identify duplex ultrasound criteria to predict
      NASCET defined 70%-99% ICA stenosis was carried out. In addition, the original
      University of Washington criteria for critical stenosis (> or = 80%) was also
      examined. The accuracy of these criteria was determined with angiographic results
      and the positive predictive value (PPV) of each criterion were compared. Ninety
      nine patients with 185 carotid bifurcations were available for comparison. The
      different duplex criteria for determining NASCET defined 70%-99% ICA stenosis
      were: ICA PSV > 175 cm/sec or PSV < 40 cm/sec, PSV > 230 cm/sec, ratio of ICA to
      CCA PSVs > 4, PSV > 130 cm/sec plus EDV > 100 cm/sec, and PSV > 270 cm/sec plus
      EDV > 110 cm/sec. When compared with angiography, the calculated PPVs for these
      criteria were 71% (73/103), 81% (71/88), 86% (67/78), 88% (62/70), and 90%
      (57/63), respectively. The University of Washington criteria for critical
      stenosis (PSV > 125 cm/sec plus EDV > 135 cm/sec) had the highest PPV at 91.6%
      (55/60). The University of Washington criteria for critical stenosis had the
      highest PPV to predict a 70%-99% angiographic stenosis.

PMID- 9588511
TI  - Complementary surgical/interventional techniques for nonresective management of
      "inoperable" aneurysms: a second look.
AB  - Induced thrombosis ("nonresective" therapy) of aortic aneurysms by distal
      arterial ligation, coil/wire embolization, and extraanatomic bypass was devalued
      by anecdotal reports emerging during the mid-1980s. Nevertheless, we have
      recently found the technique to be life-saving in occasional cases and worth
      revisiting. Since 1990, standard aortic aneurysm repair has been performed in 231
      patients (99.1% survival), endovascular aortic aneurysm repair in 6 patients
      (83.3% survival), and combined surgical/interventional "nonresective" repair of a
      variety of aneurysms in 10 patients (100% survival). Mean age of the group was
      67.9 years. Repair was performed for aortoiliac aneurysms (4), common iliac
      aneurysms (3), internal iliac aneurysms (2), and a large proximal subclavian
      artery pseudoaneurysm (1). Four of the patients had been explored and declared to
      be "inoperable" (retroperitoneal fibrosis) prior to transfer to the Columbia
      Presbyterian Medical Center. All patients survived. Aneurysm rupture has not
      occurred in any patient, but one patient with a presumably thrombosed subclavian
      pseudoaneurysm presented 26 months postcoil-induced thrombosis with progressive
      aneurysm enlargement due to incomplete aneurysm thrombosis and required repair
      using circulatory arrest. Eight of the patients remain alive (80%) at a mean
      follow-up of 40.3 months (range 14-88 months). Two patients died of malignancy
      (30 months) and cardiac disease (15 months). It is concluded that combined
      surgical/interventional techniques can be life-saving in the rare instances when
      conventional or endovascular aneurysm repair is not advisable but that complete
      aneurysm thrombosis is essential and occasionally difficult to achieve. Since
      small proximal portions of the aneurysm may remain patent and not be visualized
      on magnetic resonance imaging (MRI) or computed tomography (CT) scans, contrast
      angiographic documentation of complete aneurysm thrombosis is essential prior to
      hospital discharge and close follow-up is necessary to ascertain long-term
      adequacy of the repair. Incomplete thrombosis is suspected as a major factor in
      earlier reports of aneurysm rupture after seemingly successful nonresective
      therapy.

PMID- 9588512
TI  - The natural history of "failing" arterial bypass grafts in a duplex surveillance
      protocol.
AB  - Though color duplex ultrasonography (CDU) can identify threatened arterial bypass
      grafts, the natural history of grafts predicted to fail is not known. We examined
      patency of "failing grafts" followed by CDU for prolonged periods without
      intervention. A graft was defined as failing if there was elevation of the peak
      systolic flow velocity (PSFV) to a ratio of three times the PSFV in the adjacent
      graft, or if PSFV was less than 45 cm/sec throughout the graft. Only patients
      followed with CDU abnormalities without intervention for more than 2 months were
      included. Forty-six CDU abnormalities were noted after construction or revision
      of lower extremity bypass grafts in 34 patients. Grafts were autogenous in 25
      cases, prosthetic in 16, and composite in 5. Focal abnormalities were noted in 35
      grafts (76.1%), low PSFV throughout the graft in 6 (13.0%), while both findings
      were present in 5 grafts (10.7%). For various reasons no intervention was
      performed during follow-up ranging from 2 to 50 (mean 10) months, during which
      time patients had a mean of 3.6 CDU studies. Abnormalities regressed in 10 grafts
      (21.7%), progressed to 5 (10.9%), and were stable in the remainder. Fourteen
      grafts (30.4%) were ultimately revised with surgery or angioplasty at a mean of 5
      months after the first abnormal CDU. Only 3 grafts (6.5%) occluded while being
      followed. Two of the 3 were among the 5 grafts with both focal elevated PSFV
      ratio and low PSFV throughout the remaining graft, while all 3 were among the 7
      grafts with PSFV ratio in excess of 7.0. Compared to grafts without these
      features, occlusion was significantly more likely (p = 0.03 and p = 0.001,
      respectively). Currently defined threshold CDU criteria for prediction of graft
      failure may be excessively sensitive.

PMID- 9588513
TI  - Diagnosis of thoracic outlet syndrome using electrophysiologically guided
      anterior scalene blocks.
AB  - There is no "gold standard" for diagnosing thoracic outlet compression syndrome
      (TOS), however, anesthetic blocks of the anterior scalene muscle (ASM) have been
      used as a means of predicting which patients may benefit from surgical
      decompression. The standard technique of using surface landmarks often results in
      inadvertent somatic block and sympathetic block because there is no reliable
      verification of needle tip localization. The present study was undertaken to
      determine if needle tip localization can be improved by using
      electrophysiological guidance. ASM blocks were performed for patients with a
      diagnosis of possible TOS. An insulated hypodermic needle was inserted into the
      ASM which was identified during electromyogram (EMG) activation maneuvers.
      Stimulation was performed to make sure that the needle tip was not in the
      brachial plexus. Local anesthetic was instilled and the intensity of pain induced
      by TOS stress maneuvers was compared to pain ratings obtained after control
      injections. The ASM could be identified electromyographically in all 122 cases.
      There were no instances of inadvertent somatic block nor sympathetic block. Of 38
      patients who underwent surgical decompression of the thoracic outlet, 30 of 32
      (94%) with a positive block had a good outcome compared with 3 of 6 (50%) who
      underwent surgery in spite of a negative block. Electrophysiological guidance
      facilitates accurate needle tip placement in the performance of ASM blocks; the
      results of these blocks appear to correlate with surgical outcomes.

PMID- 9588514
TI  - Axillobifemoral bypass: elective versus emergent operation.
AB  - Axillobifemoral bypass (AxBFB) is considered an inferior operation because of
      comparatively poor long-term results. One factor that has not been considered in
      the literature is whether or not the operation is performed electively or for
      acute ischemia (< 24 hours duration). This may be a more important predictor of
      poor results than previously recognized. During the last 10 years, we have
      performed 59 AxBFB. In Group A, 41 patients (mean age 71) underwent elective
      AxBFB and in Group B, 18 patients (mean age 65) had emergency AxBFB. Indications
      for surgery in Group A were limb-threatening ischemia (30), infected aortic graft
      (5), and severe claudication (6); in Group B, indications for surgery were acute
      limb ischemia (16), and aortoduodenal fistula (2). Primary patency (p < 0.002),
      limb salvage (p < 0.002), and survival (p < 0.03) were significantly better in
      Group A versus Group B. We conclude that an AxBFB performed electively provides
      satisfactory palliation of severe vascular disease in high-risk patients. The
      indications for operation and timing of the operation may explain the widely
      disparate clinical results reported in the literature.

PMID- 9588515
TI  - Concomitant aortic and renal artery reconstruction in patients on an intensive
      antihypertensive medical regimen: long-term outcome.
AB  - A beneficial effect in blood pressure control is presumed for patients on an
      intensive preoperative antihypertensive regimen who undergo empiric renal
      revascularization. Nonetheless, a noticeable decline in surgical cure rates for
      hypertension has been recently observed in patients with generalized
      atherosclerosis. The outcome of patients on multiple preoperative
      antihypertensive agents who underwent combined aortic and renal artery
      reconstruction was reviewed. The study population comprised 43 patients who
      underwent concomitant renal artery and aortic reconstruction for atherosclerotic
      disease between 1983 and 1995 and who were taking two or more antihypertensive
      medications and had a serum creatinine of less than or equal to 1.7 mg/dL.
      Operative management included an aortic reconstruction with either unilateral (n
      = 22) or bilateral (n = 19) aortorenal bypass or renal endarterectomy (n = 2).
      Operative mortality was 4.7% (2 of 43). The estimated 5-yr probability of
      survival was 83% (95% C.I. 0.70, 0.99). Late follow-up data on blood pressure
      control were available for review in 32 patients at a median follow-up of 37
      months. Hypertension was cured in 1 (3%) and improved in an additional 15 (47%)
      patients. The numbers of antihypertensive medications taken preoperatively (mean
      = 2.7) declined at late follow-up (mean = 1.6). Notably, the largest reduction
      was observed with beta blockers (p = 0.006), central sympatholytics (p = 0.041),
      and angiotensin converting enzyme (ACE) inhibitors (p = 0.052). The number of
      preoperative antihypertensive medications was not significantly related to
      survival or to blood pressure improvement. However, uncontrolled preoperative
      hypertension despite antihypertensive therapy was associated with a favorable
      blood pressure response to operation (p < 0.001). Patients on an intensive
      antihypertensive regimen can safely undergo concomitant renal artery and aortic
      reconstruction for the empiric management of hypertension. Poorly controlled
      preoperative hypertension in the presence of multiple antihypertensive agents is
      a favorable marker for improved postoperative blood pressure control.

PMID- 9588516
TI  - "Pancake kidney": a renal anomaly complicating aortic reconstruction.
AB  - Pancake kidney is a rare fusion anomaly of the kidneys characterized by the
      presence of a displaced, lobulated pelvic renal mass of dual parenchymatous
      system without intervening septum. The existence of this anomaly during aortic
      reconstruction presents a great technical challenge. The surgical management of a
      51-year-old man with a 5.0 cm aortic aneurysm and a pancake kidney is described.

PMID- 9588517
TI  - Stent-graft repair of mycotic superficial femoral artery aneurysm using a Palmaz
      stent and autologous saphenous vein.
AB  - Developing endoluminal technology has permitted the management of selected
      aneurysms using stent-grafts, but the applicability and durability of these new
      devices has not yet been proven. Standard treatment of mycotic aneurysms
      generally requires arterial ligation, excision and debridement, and autologous or
      extraanatomic synthetic bypass. A saphenous vein-covered stent was used to
      exclude an expanding, mycotic, superficial femoral artery aneurysm in a
      critically ill patient. Although stent-graft exclusion was intended as a bridge
      to standard therapy, the mass resolved, the superficial femoral artery remains
      patent, and the patient is symptom-free at 1 year without further intervention.
      Additional experience is required to determine whether stent-grafts have a role
      in the management of mycotic aneurysms.

PMID- 9588518
TI  - Aneurysms of the pancreaticoduodenal arteries: a change in management.
AB  - Since the first report of an aneurysm involving the pancreaticoduodenal arteries
      a century ago, only 83 cases have been reported in our collective review of the
      English literature. Their presentation varies from indistinct abdominal pain to
      hemorrhagic shock, often making the diagnosis onerous. The mortality rate in this
      patient group has been significant, and in cases reported since 1980, the
      mortality rate remains at 17% (7 deaths/42 reported cases). Surgery has been, and
      continues to be, the cornerstone of therapy, with an incumbent mortality rate of
      19% (5 deaths/26 patients treated surgically since 1980). This case report and
      100-year review of the literature describes the causes, natural history, and
      historic management of pancreaticoduodenal artery aneurysms. Most importantly, it
      demonstrates the use of angiographic embolization in the definitive management of
      these aneurysms with no mortality.

PMID- 9588519
TI  - The use of omental flaps in abdominal aortic surgery: a review and description of
      a simple technique.

PMID- 9588520
TI  - Value of an endovascular suite in the operating room.
AB  - The purpose of this study is to describe the advantages and value of an
      endovascular suite in the operating room from a vascular surgeon's perspective.
      All endovascular procedures were performed in a specially equipped operating room
      by vascular surgeons using digital fluoroscopic imaging equipment. Between
      January 1, 1994 and August 31, 1996, intraoperative balloon angioplasties were
      attempted by vascular surgeons in 102 patients with insertion of 22 stents.
      Angioplasties were performed for stenoses in 50 arterial bypasses and 25 iliac,
      17 femoral and 10 popliteal arteries proximal or distal to arterial grafts. Sixty
      two procedures were performed concomitantly with a surgical bypass and 40 were
      performed as the sole procedure (30 percutaneous, 10 open) in patients who had
      previously undergone a bypass. There were five technically unsatisfactory results
      which were converted to surgical procedures and one postoperative hematoma that
      required surgical repair. Ninety of the 102 grafts remained patent more than 1
      month after the procedure. Establishment of an endovascular operating room suite
      enables vascular surgeons to perform adjunctive endovascular procedures
      concomitantly with vascular surgery and treat unexpected findings in the
      operating room amenable to endovascular intervention without requesting other
      interventionalists to participate on an emergent basis.

PMID- 9588521
TI  - Operative management of chronic mesenteric ischemia.

PMID- 9588522
TI  - Retrograde hepatic venous flow: a sign of mesenteric infarction.

PMID- 9588524
TI  - Study of the maturation of the child's brain using 31P-MRS.
AB  - The maturation of human cerebrum and cerebellum in 37 normal children aged 4
      months to 13 years 8 months was evaluated by 31P-magnetic resonance spectroscopy
      using two different conditions of repetition time (TR) (TR = 3 seconds and 15
      seconds) in each region. The results were as follows. First, the PME/PDE,
      PCr/gamma-ATP and Pi/PCr ratios differed between the cerebrum and the cerebellum.
      The PME/PDE and PCr/gamma-ATP ratios were greater in the cerebellum than in the
      cerebrum. However, the Pi/PCr ratio was smaller in the cerebellum than in the
      cerebrum. At TR = 3 seconds, the ratio of (PME/PDE ratio in the
      cerebellum)/(PME/PDE ratio in the cerebrum) and the ratio of (PCr/gamma-ATP ratio
      in the cerebellum)/(PCr/gamma-ATP ratio in the cerebrum) manifested a nearly
      constant value independent of age. Second, the phosphomonoester peak in the
      cerebrum contained a substance with a longer relaxation time than 3 seconds; this
      substance was present in large amounts in the early period, then gradually
      decreased during maturation.

PMID- 9588523
TI  - Outcome of children with cerebral edema caused by fulminant hepatic failure.
AB  - Mortality is high in patients with fulminant hepatic failure (FHF). Neurologic
      complications of encephalopathy and cerebral edema are major contributors to
      mortality. Orthotopic liver transplantation has improved survival in these
      patients. However, the complexity of medical and surgical problems in this
      patient population, coupled with a severe shortage of organs, requires careful
      patient selection. The aim of this study was to describe the neurologic outcome
      of children with FHF who developed radiologically apparent cerebral edema. The
      hospital and outpatient records and radiologic studies of 20 children with FHF
      admitted to Children's Hospital of Pittsburgh from 1981-1995 who developed
      encephalopathy and computed tomographic evidence of cerebral edema were reviewed.
      Fourteen patients died (70%), three were left with severe neurologic deficits
      (15%), and three were left with moderate deficits (15%). Survival was correlated
      with a lesser degree of coma. Histopathologic examination of eight brains
      demonstrated cerebral edema and widespread ischemic neuronal necrosis in all
      eight. The presence of radiographic cerebral edema in children with FHF is an
      objective measure that indicates a very poor prognosis. Termination of care is a
      reasonable option. Comprehensive monitoring of cerebral function and intracranial
      pressure is required in children with FHF. Orthotopic liver transplantation
      should be performed in children with severe and worsening encephalopathy before
      the development of radiographically apparent cerebral edema.

PMID- 9588525
TI  - Serum ionized magnesium in premature and term infants.
AB  - Magnesium is the element with the second highest concentration in the body and is
      found almost entirely in the intracellular compartment. The small serum component
      gives a poor representation of the active, physiologic state of the metal. This
      state is assessed much better by measuring ionized magnesium in the serum, which
      can now be performed with a sensitive ion-selective electrode. This study was
      undertaken to establish the normal serum ionized magnesium levels in newborn
      infants and to define normal serum ionized calcium/ionized magnesium ratios.
      Ninety-seven infants were investigated. Six were born before 32 weeks gestation,
      28 between 33 and 37 weeks gestation, and 63 were term. Ionized magnesium levels
      were 0.69 +/- 0.14 mmol/L, 0.63 +/- 0.10 mmol/L, and 0.57 +/- 0.07 mmol/L in each
      group, respectively. These findings demonstrate a significant decline in serum
      ionized magnesium with increasing maturity. This decrease may relate to a greater
      need for magnesium uptake during earlier gestation, more magnesium-induced
      vasodilation to maintain adequate blood flow to developing tissues and organs, or
      immature parathormone function earlier in pregnancy. The progressive rise in
      serum ionized calcium/ionized magnesium ratios found herein supports the latter
      hypothesis.

PMID- 9588526
TI  - Electroretinogram in Duchenne/Becker muscular dystrophy.
AB  - The authors studied all cases with dystrophinopathy consecutively reviewed
      between May 1995 and December 1996 by means of electroretinography (ERG), which
      was recorded using skin eyelid electrodes and with standard flash stimulation.
      This methodology can detect the functional abnormalities associated with
      dystrophinopathies. The most valuable parameter is the ratio of B-wave amplitude
      to A-wave amplitude (B/A amplitude ratio), which was greater than 2 in all normal
      control patients (n = 10) and nondystrophinopathic muscular dystrophy (MD)
      patients (n = 2). It was less than 2 in 100% (n = 16) of Duchenne muscular
      dystrophy (DMD) patients (mean ratio 0.73; range 0.4-1.26). It was less than 2 in
      71% (n = 7) of Becker muscular dystrophy (BMD) patients (mean ratio 1.12; range
      0.88-1.37), and less than 2 in 50% (n = 4) of definitive DMD carriers. Twenty
      nine percent of BMD, 50% of DMD carriers, and the only case with asymptomatic
      dystrophinopathy had normal ratios (greater than 2). The differences between the
      mean ratios of control, DMD, and BMD groups were statistically significant, all
      of them with P < 0.001. ERG abnormalities of dystrophinopathies were associated
      with the more severe muscular phenotype but not with the presence or location of
      gene deletion. ERG is an easy and simple technique that is useful in cases of
      suspected dystrophinopathy with a nonconclusive molecular study. It is less
      useful in patients who are DMD carriers.

PMID- 9588527
TI  - Long-term outcomes of pediatric moyamoya disease monitored to adulthood.
AB  - The long-term outcomes of 25 patients with childhood moyamoya disease (18 with
      the transient ischemic attack [TIA] type and seven with the non-TIA type), who
      were monitored to adulthood (older than 20 years of age), were evaluated in terms
      of residual clinical symptoms, intellectual development, and activities of daily
      living. Surgical treatment was performed in ten patients,
      encephaloduroarteriosynangiosis in nine, and superficial temporal artery to
      middle cerebral artery anastomosis plus encephalomyosynangiosis in one. Only
      seven with the TIA type (three surgically and four medically treated)
      demonstrated good activities of daily living without TIA or headache and normal
      IQ. Two patients with the TIA type and three with the non-TIA type demonstrated
      poor outcomes. Three of these patients with poor outcomes had renal artery
      stenosis. Surgery was effective in nine. Since the long-term outcomes of patients
      with childhood moyamoya disease are generally poor, surgical treatment is
      believed to be an effective procedure for preventing the progression of clinical
      symptoms.

PMID- 9588528
TI  - Hypocalcemic induced increase in creatine kinase in rats.
AB  - Calcium plays an important role in various myopathies. We report on an animal
      model with increased plasma creatine kinase (CK) resulting from hypocalcemia that
      will provide clues for studying human hypocalcemic myopathy. Male Wistar rats
      were pair-fed either a control or a calcium- and vitamin D3-deficient diet for 1,
      2, 3, 4, or 5-6 weeks after weaning (3 weeks old). In the deficient diet-fed
      rats, plasma creatine kinase was increased and was accompanied by marked
      hypocalcemia. The omission of calcium and vitamin D3 from the diet for 1 or 2
      weeks was enough to cause increased plasma creatine kinase; the creatine kinase
      ratio of deficient diet-fed rats to controls was 4.84 (1,777 IU L(-1)/367 IU L(
      1)), and the calcium ion ratio was 0.41 (1.8 mg dL(-1)/4.4 mg dL(-1)) after 2
      weeks. These values returned to control levels on treatment of the rats with the
      control diet and 1alpha-OH-vitamin D3 for 1 week.

PMID- 9588529
TI  - Effect of carnitine on valproic acid concentrations in serum, brain, and liver.
AB  - This study investigates the influence of L-carnitine supplementation on valproic
      acid concentrations in rat serum, brain, and liver. Carnitine supplementation
      increased carnitine concentrations significantly in serum and liver but not in
      the brain. Free valproic acid concentrations in the brain were significantly
      increased by carnitine supplementation without any change of carnitine
      concentrations in the brain. The increase of serum-free valproic acid
      concentrations by carnitine supplementation apparently caused brain-free valproic
      acid concentrations to increase. This study suggests that L-carnitine
      supplementation to valproic acid therapy may potentiate valproic acid effects in
      the brain, even when the clinical dosage in humans is used.

PMID- 9588530
TI  - An MRI and MRS study of Pelizaeus-Merzbacher disease.
AB  - Earlier reports on T2-weighted magnetic resonance imaging (MRI) in the classical
      form of Pelizaeus-Merzbacher disease seemed to divide the patterns of the high
      intensity lesions in the white matter into three subtypes: type I, diffusely
      hemispheric and corticospinal; type II, diffusely hemispheric without brainstem
      lesions; and type III, patchy in the hemispheres. The four boys presented in our
      study, between 10 and 17 years of age, with classical Pelizaeus-Merzbacher
      disease, who all had a duplicated proteolipid protein gene, invariably manifested
      type I despite their various clinical severities. Follow-up MRI after an interval
      of 5 years and proton magnetic resonance spectroscopy was performed in three of
      the patients. The white matter on the last MRI was unchanged in volume and the
      distribution of high-intense areas. Proton magnetic resonance spectroscopy
      revealed no abnormal peaks. These results were consistent with the lack of
      definite neurologic regression in the last 5 years and with the pathologic
      characteristics of well-preserved axons and the absence of sclerosis. Further
      study is required to precisely determine whether the patterns of MRI findings can
      be divided into subtypes corresponding to those of proteolipid protein gene
      abnormalities.

PMID- 9588531
TI  - Sjogren-Larsson syndrome: postmortem brain abnormalities.
AB  - Brain abnormalities were described in a patient who had experienced Sjogren
      Larsson syndrome (SLS) with typical clinical signs. Examination of the brain
      revealed (1) accumulation of peculiar lipoid substances stained lightly with
      periodic acid-Schiff (PAS) in the subpial, subependymal, and perivascular glial
      layers, the subpial and perivascular spaces, and the white matter of the cerebrum
      and brainstem; (2) proliferation of perivascular macrophages containing
      lipofuscin-like pigments; (3) dense distribution of round or ellipsoid small
      bodies stained strongly with PAS in the subpial, subependymal, and perivascular
      glial layers and the white matter; (4) appearance of spheroid bodies in the
      neuropil of relay nuclei (the lateral geniculate body, pontine nuclei, inferior
      olivary nucleus, posterior funicular nucleus, and dentate nucleus) and the white
      matter; and (5) reduction of myelinated nerve fibers in the cerebral and
      cerebellar white matter. Six-layered neuronal cytoarchitecture was preserved in
      the cerebral neocortex, except for the insula where pyramidal neurons were
      arranged at random. The exact mechanisms remain unclear, but it is suggested that
      peculiar lipoid substances may accumulate in the specific regions of the brain
      and that neuronal and astrocytic processes may be primarily affected in SLS.

PMID- 9588533
TI  - Startle-induced epilepsy in a patient with epidermal nevus syndrome.
AB  - Startle-induced epilepsy was observed in a 5-year-old boy with epidermal nevus
      syndrome. He manifested linear nevus on the face and neck, mild mental
      retardation, and right hemiparesis. Massive myoclonus, followed by tonic
      seizures, had been triggered by unexpected auditory stimuli since 3 years of age.
      The startle-induced seizures were the only epileptic manifestation. Interictal
      EEG occasionally depicted spontaneous focal spikes and waves in the left
      frontotemporal area, and ictal EEG depicted vertex spikes and then diffuse slow
      spike-and-wave complex bursts. Left frontal and perisylvian cortical atrophy and
      a white matter abnormality in the left frontal area were revealed by magnetic
      resonance imaging. Single photon emission computed tomography demonstrated
      diffuse low perfusion in the left cerebral hemisphere. Lower amplitude potentials
      in the left cerebral cortex were evident during somatosensory evoked potential
      evaluation. These results indicate that hemispheric dysfunction could cause
      startle-induced epilepsy in this patient.

PMID- 9588532
TI  - Strokes, cutis marmorata telangiectatica congenita, and factor V Leiden.
AB  - Cutis marmorata telangiectatica congenita is an uncommon, congenital cutaneous
      condition typified by persistent cutis marmorata and other associated
      abnormalities. Progressive neurologic complications are generally not a feature
      of the disorder. A case is reported of cutis marmorata telangiectatica congenita
      associated with diffuse cerebrovascular infarcts at 7 months of age. Moyamoya
      like vascular abnormalities were demonstrated in addition to the factor V Leiden
      mutation, a congenital hypercoagulable disorder. This novel case illustrates the
      importance of evaluating children with strokes for congenital thrombophilic
      disorders.

PMID- 9588534
TI  - Bilateral facial palsy caused by bilateral masked mastoiditis.
AB  - Acquired simultaneous bilateral facial palsy caused by bilateral masked
      mastoiditis in a 25-month-old girl is reported. After the administration of
      antibiotics for 10 days for treatment of bilateral acute otitis media, overt
      signs of otitis media diminished as bilateral facial palsy ensued. For diagnosis
      of masked mastoiditis, brain magnetic resonance imaging was of significant value
      in our case. The findings in this case suggest that masked mastoiditis should be
      considered as a cause of bilateral facial palsy, as well as unilateral facial
      palsy.

PMID- 9588535
TI  - Rotavirus encephalitis mimicking afebrile benign convulsions in infants.
AB  - A 2-year-old-boy had rotavirus gastroenteritis and demonstrated afebrile partial
      seizures with secondary generalization. The presence of rotavirus genome and anti
      rotavirus IgG was detected in the cerebrospinal fluid. The genotype of VP4 was P8
      and that of VP7 was G4. The imaging analysis by computed tomography and single
      photon emission computed tomography implied encephalitis. The seizures were well
      controlled by standard antiepileptic therapy, and the child experienced normal
      development with neither physical nor neurologic sequelae, which appeared to
      mimic benign infantile partial epilepsy.

PMID- 9588536
TI  - A DNA repair defect in a patient with ataxia, mental retardation, and short
      stature.
AB  - A 12-year-old girl developed ataxia that gradually progressed. At age 18 the
      patient presented with mental retardation, cachectic dwarfism, microcephalus, and
      a progeroid appearance but no photosensitive skin lesions or deafness. On
      analysis of fibroblasts, unscheduled DNA synthesis was reduced to 50% of normal,
      but colony-forming ability after ultraviolet irradiation was normal. The symptoms
      and phenotype of the patient were distinguished from those in Cockayne syndrome
      and xeroderma pigmentosum. This case is interesting because the defect in DNA
      repair after ultraviolet irradiation was detected in a patient with neurologic
      disturbances but without photosensitive skin lesions.

PMID- 9588537
TI  - Microlissencephaly.
AB  - An inbred Arab family with three neonates affected by microlissencephaly syndrome
      is reported. Brain magnetic resonance imaging in the index case revealed very
      thin brain mantle with agyria-pachygyria, agenesis of the corpus callosum, and
      hypoplasia of the brainstem and cerebellum. All three neonates had microcephaly,
      arthrogryposis multiplex congenita, and micropenis. The presence of three
      affected newborn infants in a consanguineous family suggests an autosomal
      recessive mode of inheritance of this syndrome. The spectrum of
      microlissencephaly syndrome is reviewed.

PMID- 9588538
TI  - Hypertrophic cardiomyopathy in congenital myotonic dystrophy.
AB  - Involvement of the cardiac conduction system is a common clinical feature in
      myotonic dystrophy, whereas the association of primary myocardial abnormalities
      has rarely been reported. A patient with a severe form of congenital myotonic
      dystrophy who developed fatal left ventricular hypertrophy at 3 months of age and
      died at 2 years of age is reported. Serial ultrasonographic studies revealed
      progressive left ventricular hypertrophy accompanied by outflow obstruction of
      the left ventricle. Southern analysis for the myotonin kinase gene revealed a 5.8
      kb expansion of CTG repeats in addition to a fragment of normal length. The
      degree of expansion was much greater than those of other reported patients with
      congenital myotonic dystrophy. These findings suggest that left ventricular
      hypertrophy represents an extreme level of myocardial damage in myotonic
      dystrophy and that this damage may be related to the larger size of the CTG
      repeats.

PMID- 9588539
TI  - A proposed comprehensive grading system to predict outcome for surgical
      management of intracranial aneurysms.
AB  - OBJECTIVE: By conducting a review of clinical outcomes for patients with
      aneurysms treated using current microneurosurgical techniques and intensive care
      unit management, we determined that grading systems based only on the clinical
      condition of the patient failed to produce a significant stratification of
      outcome between individual grades of patients. We hypothesized that outcome
      prediction for patients surgically treated for intracranial aneurysms could be
      improved by including factors other than clinical condition that were also
      strongly associated with outcome. METHODS: To identify potential factors for
      inclusion in a risk prediction tool, we conducted a multivariate logistic
      regression analysis of patient- and lesion-specific factors suspected to be
      associated with outcome in a series of 434 aneurysm operations. Factors that were
      strongly associated with outcome were used to develop a comprehensive grading
      system. In the system, 1 point is assigned for Hunt and Hess Grade IV or V,
      Fisher Scale score of 3 or 4, aneurysm size greater than 10 mm, patient age older
      than 50 years, and if the lesion is a giant (> or =25 mm) posterior circulation
      lesion. By adding the total points, a 5-point grading system (Grades 0-5) is
      obtained. RESULTS: Age of patient, size of aneurysm, severity of subarachnoid
      hemorrhage (Fisher Scale evaluation of density of blood present as revealed by
      computed tomography), and clinical condition (Hunt and Hess grade) were each
      independently and strongly (relative risk, >4) associated with long-term outcome.
      In addition, there was a trend for increased risk with larger (>25 mm) posterior
      circulation lesions. When applied to the study population, individual grades on
      the new grading scale correlated well with actual outcome. In a prospective
      assessment of the system as applied to an additional 72 operations with at least
      1 year of follow-up, the correlation of individual grades and outcome was strong
      and validated the retrospective findings. CONCLUSION: This new grading system is
      easy to apply, separates patients into groups with markedly different outcomes,
      and is comprehensive, allowing for more accurate prediction of surgical outcome
      for both unruptured and ruptured cerebral aneurysms.

PMID- 9588540
TI  - Intracranial aneurysms and sickle cell anemia: multiplicity and propensity for
      the vertebrobasilar territory.
AB  - OBJECTIVE: We describe a case of sickle cell anemia and multiple intracranial
      aneurysms and review the English-language-reported cases of sickle cell disease
      associated with intracranial aneurysms proven angiographically or by autopsy, to
      assess whether there are associations with aneurysm multiplicity and sites of
      aneurysm occurrence. CLINICAL PRESENTATION: A 28-year-old woman with sickle cell
      disease and a subarachnoid hemorrhage underwent successful clipping of three
      intracranial aneurysms. RESULTS: Among 44 reviewed cases, 57% of patients
      demonstrated multiple aneurysms, and aneurysms from patients with multiple
      aneurysms comprised nearly 80% of the total number of aneurysms. There were, on
      average, three aneurysms per patient for patients with multiple aneurysms. There
      was a predominance of female patients (female/male ratio, 1.6:1), although there
      existed no significant differences in age or gender for patients with single or
      multiple aneurysms. None of the patients with multiple aneurysms was older than
      40 years of age at the time of presentation. Patients with multiple aneurysms and
      sickle cell disease showed a significant difference in the distribution of the
      aneurysm sites, with a significantly large number occurring in the
      vertebrobasilar axis. Multiple aneurysms associated with sickle cell disease
      showed a higher rate of simultaneous occurrence in the posterior and anterior
      circulation, compared with multiple aneurysms in the general population.
      CONCLUSION: There are strong statistical associations for aneurysm multiplicity
      and sites of aneurysm occurrence among reported patients with sickle cell
      disease. Patients with sickle cell anemia and neurological symptoms should
      undergo magnetic resonance angiography or four-vessel angiography to detect
      potentially harmful, but neurosurgically treatable, pathological conditions.

PMID- 9588541
TI  - The efficacy and safety of angioplasty for cerebral vasospasm after subarachnoid
      hemorrhage.
AB  - OBJECTIVE: Cerebral angioplasty is being increasingly used for symptomatic
      vasospasm secondary to subarachnoid hemorrhage. We attempted to determine the
      safety and efficacy of angioplasty for refractory vasospasm. We also looked at
      the influence of timing of angioplasty on outcome. METHODS: We retrospectively
      studied patients with subarachnoid hemorrhage who underwent angioplasty in our
      institution to determine the safety and the success rate achieved with this
      procedure. The study period extended from August 1993 until February 1997.
      Clinical and radiological data were collected, with emphasis on clinical
      improvement after angioplasty and its relationship with timing of intervention.
      Thirty-one patients with 43 aneurysms and one case of arteriovenous malformations
      were included. Their ages varied between 28 and 68 years, with an average age of
      44 years. Five patients were assigned Hunt and Hess Grade IV, 15 were assigned
      Grade III, 7 were assigned Grade II, and 4 were assigned Grade I. All patients
      except two underwent angioplasty after aneurysm clipping or coiling. RESULTS:
      Angioplasty was performed an average of 6.9 days after the occurrence of
      subarachnoid hemorrhage, with a range from 1 to 14 days. It was performed early
      (within 24 h) after refractory clinical deterioration in 21 patients. A total of
      81 vessels were dilated. Three angioplasty-related complications occurred: two
      femoral hematomas and one retroperitoneal hematoma. Clinical improvement was
      dramatic after 12 procedures, moderate after 11 procedures, and minimal or
      nonexistent after 9 procedures. There was a clear tendency toward more
      significant improvement in patients with earlier angioplasty (<24 h from onset of
      neurological deficit) (P=0.0038). At discharge, 8 patients had achieved good
      recoveries (Glasgow Outcome Scale score of 1), 11 had moderate disabilities
      (Glasgow Outcome Scale score of 2), and 10 had severe disabilities (Glasgow
      Outcome Scale score of 3). Two deaths were encountered, and they were unrelated
      to angioplasty. Follow-up was obtained for 27 patients: 25 had good outcomes, 1
      was moderately disabled, and 1 died. There was no significant correlation between
      interval and outcome. CONCLUSION: Our results indicate that angioplasty is a safe
      and effective treatment for symptomatic vasospasm that is refractory to
      hyperdynamic hypervolemic therapy. When used early (<24 h), it leads to
      significant clinical improvement. However, the long-term outcome is good, even in
      cases of delayed angioplasty. The prevention of worsening of the cerebral
      ischemia and its extension to other territories may be the reason.

PMID- 9588542
TI  - Influence of degree of carotid artery stenosis and collateral pathways and effect
      of carotid endarterectomy on cerebral vasoreactivity.
AB  - OBJECTIVE: The goal was to determine the influence of the degree of internal
      carotid artery (ICA) stenosis and collateral pathways on cerebral vasoreactivity
      (CVR). The effect of carotid endarterectomy on CVR is also presented. METHODS:
      For 36 patients with unilateral ICA stenosis of at least 70%, regional cerebral
      blood flow (rCBF) and regional CVR (rCVR) were investigated before and after
      carotid endarterectomy, with resting and acetazolamide-challenge single photon
      emission computed tomographic scans. The degree of ICA stenosis and the status of
      the collateral pathways (sizes of the A1 segment and the posterior communicating
      artery) were evaluated by angiography. RESULTS: Thirteen patients were classified
      as Type N/N (normal rCBF and normal rCVR), 5 as Type R/N (reduced rCBF and normal
      rCVR), 6 as Type N/R (normal rCBF and reduced rCVR), and 12 as Type R/R (reduced
      rCBF and reduced rCVR). The degree of ICA stenosis correlated with rCVR status.
      The size of the A1 segment was a second-rank factor and was less effective in
      affecting rCVR. The size of the posterior communicating artery was not associated
      with rCVR. The predictive value of reduced rCVR for postoperative improvement
      (100%) was significantly higher than that of reduced rCBF (50%). CONCLUSION: The
      present results indicate that the degree of ICA stenosis is a more significant
      determinant of CVR than are the collateral pathways in patients with carotid
      artery stenosis. The high predictive rate of reduced rCVR for postoperative
      improvement implies that acetazolamide-challenge single photon emission computed
      tomographic scanning might be useful in selecting patients with asymptomatic ICA
      stenosis who might benefit from carotid endarterectomy.

PMID- 9588543
TI  - Failure in radiosurgery treatment of cerebral arteriovenous malformations.
AB  - OBJECTIVE: The aim of this study was to retrospectively analyze the reasons for
      the failure of radiosurgical treatment of cerebral arteriovenous malformations
      (AVMs). METHODS: Seventeen cases of noncured AVMs were reviewed 3 years after
      radiosurgical treatment. Follow-up ranged from 33 to 54 months (mean, 44.3 mo).
      Lesion dimensions varied from 9 to 55 mm (mean, 29.2 mm). The lesions were
      located in critical or near-critical brain regions. Angiography was performed
      under Talairach's stereotactic conditions. Two large AVMs bled 36 and 39 months
      after receiving irradiation, respectively. These two AVMs had been incompletely
      irradiated. RESULTS: Retrospectively, in four cases (23.5%) we observed errors in
      determining AVM target shape and size because of inaccurate definition of the
      nidus and/or because of stereoangiographic incompleteness (absence of external
      carotid artery injections). In five large and/or irregularly shaped AVMs (29.4%),
      a strategy of partial volume irradiation had been used. In one patient (5.8%), we
      observed the recanalization of previously embolized AVMs. In another case (5.8%),
      the target had been partially missed. The AVMs in one case (5.8%) had been
      treated with an ineffective peripheral dose. In one (5.8%), the failure occurred
      because of the lesion angio-architecture. In four cases (23.5%), no evident
      reasons for failure were determined. CONCLUSION: The results of this study
      suggest the necessity of complete irradiation of the nidus. The strategy of
      partial volume irradiation might be avoided, even if it necessitates lowering the
      doses to treat large AVMs. Accuracy in the target determination is required, and
      complete stereoangiography is necessary.

PMID- 9588544
TI  - Qualitative versus quantitative assessment of cerebrovascular reserves.
AB  - OBJECTIVE: Quantitative studies of cerebral blood flow (CBF) combined with a
      vasodilatory challenge have defined a subgroup of patients with symptomatic
      carotid occlusion who have an increased risk for stroke. These are patients whose
      CBF paradoxically decreases in response to a vasodilatory challenge. Recent
      reports suggest that qualitative CBF techniques, such as single photon emission
      tomography with 99m-hexamethylpropyleneamine oxime, can also define the same high
      risk subgroup. To determine whether qualitative measures of CBF are sufficient
      for predicting the risk of stroke, we converted our quantitative CBF data,
      obtained with xenon-enhanced computed tomography (Xe/CT), to qualitative ratios
      in a manner similar to that used with single photon emission tomography data.
      METHODS: We analyzed CBF values within the territory of the middle cerebral
      artery for 94 patients with symptomatic carotid occlusion. Values obtained using
      Xe/CT before and after the intravenous administration of 1 g of acetazolamide
      were used to derive an asymmetry index: (Coccl - Cnon)/Cavg x 100. The difference
      between the postacetazolamide asymmetry index and the baseline asymmetry index
      was used to classify the patients into groups according to CBF values. The
      threshold for abnormal qualitative CBF reactivity was defined as a percent change
      in the asymmetry index of less than -10%. Quantitative (Xe/CT) CBF was considered
      abnormal ("steal" response) when the response to acetazolamide (percent change)
      on the occluded side was a decrease of 5% or greater. RESULTS: Of 34 patients
      whose cerebrovascular reserves were considered compromised based on qualitative
      criteria, 17 (50%) did not have a steal response as defined by quantitative Xe/CT
      CBF (i.e., false positive). Eleven of 62 (18%) who were not considered
      compromised by qualitative criteria had a steal response (i.e., false negative).
      Our data indicate that a qualitative approach has a 61% sensitivity and a 75%
      specificity for detecting patients with compromised reserves. Further, the
      positive predictive value of this method is only 50%. Therefore, the two
      methodologies do not predict the same patients as having compromised reserves.
      CONCLUSION: Previous studies have shown that patients at high risk for stroke can
      be identified with quantitative CBF methods. This study shows that the important
      subgroup cannot be accurately defined with qualitative methodology. The
      implications of using the more reliable methodology are important for individual
      patient management and for designing clinical trials.

PMID- 9588545
TI  - Recent results of secondary transnasal surgery for residual or recurring
      acromegaly.
AB  - OBJECTIVE: The results of secondary surgery for either residual or recurring
      acromegaly have been reported to be unfavorable. To evaluate the effectiveness of
      recent techniques of secondary transnasal microsurgery, we analyzed the surgical
      results of remnant or recurring acromegaly in patients who underwent secondary
      transnasal surgery from 1990 to 1996. METHODS: Secondary transnasal explorations
      were performed in 28 acromegalic patients (mean age+/-standard error, 39+/-2.3
      yr) who had been previously treated with microsurgery (patients at our
      institutions, n=5; patients at other institutions, n=23). For most of these
      patients, medical treatment after primary surgery was unsatisfactory. Magnetic
      resonance imaging demonstrated 18 transnasally resectable tumors (64.3%) and 10
      nonresectable grossly invasive tumors (35.7%). Surgical indication was based on
      elevated plasma growth hormone (GH) levels and evidence of tumor revealed by
      magnetic resonance imaging. RESULTS: Intraoperative GH measurement was performed
      in all patients. In 13 of 18 patients with resectable tumors, the surgical
      assessment with sufficient GH decline intraoperatively was likewise judged as
      complete and was later proved. In three of five patients with inadequate GH
      decline, endocrinological remission was achieved by performing further surgery.
      Thus, an endocrinological remission was achieved in 16 of 18 patients (88.9%)
      with resectable tumors. In 10 patients with nonresectable tumors, the tumor mass
      was further reduced. Overall, the endocrinological remission rate was 57.1% (16
      of 28 patients). There was no serious morbidity and there was no mortality in
      this series. CONCLUSION: We conclude that in patients with transnasally
      resectable tumor residuals or recurrences confirmed by magnetic resonance
      imaging, endocrinological remissions can be obtained with high probability, even
      in secondary surgery after an unsuccessful previous operation.

PMID- 9588546
TI  - Chemotherapy for advanced esthesioneuroblastoma: the Mayo Clinic experience.
AB  - OBJECTIVE: Esthesioneuroblastoma (olfactory neuroblastoma) is a rare
      neuroendocrine tumor that arises in the upper nasal cavity from the olfactory
      epithelium. Little information is available regarding the treatment of these
      tumors with chemotherapy in the advanced setting. A retrospective review of
      patients with recurrent esthesioneuroblastoma treated with chemotherapy between
      1970 and 1995 at the Mayo Clinic was undertaken to gain more information
      regarding the efficacy of chemotherapy treatment for these patients. METHODS: Ten
      patients were identified using a computerized data base available at this
      institution. The clinical and pathological materials, when available, were
      reviewed, and each tumor reviewed was assigned a Hyams' grade. RESULTS: There
      were six men and four women, ranging in age from 22 to 74 years, all of whom had
      assessable Kadish Stage C disease at the time of chemotherapy treatment. The
      chemotherapy regimens and clinical follow-up varied during this 25-year time
      span. The only tumor regression resultant from chemotherapy was observed in
      patients with high-grade tumors. Two of four patients with high-grade tumors
      obtained regression from first-line, platinum-based chemotherapy, with a mean
      duration of regression of 9.3 months (range, 2-13 mo). Survival time from initial
      diagnosis was 139.5 months (range, 83-168 mo) in patients with low-grade tumors
      and 32.2 months (range, 5-84 mo) in patients with high-grade tumors. Survival
      from initial chemotherapy treatment was 44.5 months (range, 3-130 mo) in patients
      with low-grade tumors and 26.5 months (range, 2-67 mo) in patients with high
      grade tumors. CONCLUSION: Hyams' grading of esthesioneuroblastoma tumors seems to
      be important in predicting response to chemotherapy. Despite sensitivity to
      platinum-based chemotherapy, patients with high-grade tumors in this series had a
      much more aggressive course than did those with lower-grade tumors. This series
      suggests that cisplatin-based chemotherapy is active in advanced, high-grade
      esthesioneuroblastoma and is a reasonable choice in the systemic treatment of
      these patients.

PMID- 9588547
TI  - The role of preoperative adjuvant treatment in the management of
      esthesioneuroblastoma: the University of Virginia experience.
AB  - OBJECTIVE: Multidisciplinary management of esthesioneuroblastoma has effected
      markedly increased survival during the past 20 years. The potential for radical
      craniofacial surgery for complete en bloc resection, the availability of advanced
      neuroimaging modalities, and the incorporation of neoadjuvant therapy into
      treatment strategies for tumor remission have all contributed to this
      accomplishment. However, a standard protocol for the management of these lesions
      has not been accepted; preoperative radiation and chemotherapy have been
      advocated, but neither radiographic nor clinical response has been quantified.
      METHODS: Thirty-four consecutive patients with biopsy-proven
      esthesioneuroblastoma treated at one institution from 1976 to 1994 were reviewed
      to determine the effects of preoperative radiation therapy, with or without
      chemotherapy, on tumor size and long-term survival. RESULTS: In a multivariate
      regression analysis, advanced age was predictive of decreased disease-free
      survival (P=0.008), whereas advanced Kadish stage was associated with a
      borderline higher rate of disease-related mortality (P=0.056). Two-thirds of the
      patients showed a significant reduction in tumor burden with adjuvant therapy.
      Patients with response to neoadjuvant therapy demonstrated a significantly lower
      rate of disease-related mortality (P=0.050). In this series, the overall 5- and
      10-year survival rates were 81.0 and 54.5%, respectively. CONCLUSION:
      Preoperative neoadjuvant therapy provides a valuable complement to radical
      craniofacial resection, leading to reduction in tumor burden. Patients
      experiencing reduction in tumor volume by neoadjuvant therapy demonstrate an
      improved prognosis.

PMID- 9588548
TI  - Radiation therapy and malignant degeneration of benign supratentorial
      gangliogliomas.
AB  - OBJECTIVE: Gangliogliomas are indolent tumors comprised of neoplastic glial and
      neuronal cells. Benign lesions tend to be associated with long survival unless
      the tumor degenerates to a histologically malignant form. This study reviews four
      cases of histologically proven benign ganglioglioma that later demonstrated
      malignant features within the glial component of the tumor. Features common to
      each case are analyzed, and similar cases from the literature are reviewed.
      METHODS: The records of 42 supratentorial gangliogliomas operated on at our
      institution since 1985 were reviewed. Special attention was paid to histological
      characteristics, use of adjuvant radiotherapy, time to tumor recurrence, and
      histology of the recurrent tumor. RESULTS: Of the 42 cases of gangliogliomas, 29
      were initially histologically benign. Of these 29, 14 received postoperative
      radiation therapy and 14 did not; it was unclear whether one patient received
      adjuvant radiotherapy, and this patient was excluded from further analysis. Four
      benign gangliogliomas exhibited malignant degeneration of the glial component.
      These four all occurred in patients who had undergone postoperative irradiation.
      The time to identified histological change within recurrent tumors averaged 65
      months (range, 22-144 mo). CONCLUSION: All of the benign gangliogliomas
      undergoing malignant change had postoperative radiation therapy as a common
      feature. This represents a potential correlation that requires further study.

PMID- 9588549
TI  - Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of
      parenchymal tumors.
AB  - OBJECTIVE: The goals were to critically review all complications resulting within
      30 days after craniotomies performed for excision of intra-axial brain tumors
      relative to factors likely to affect complication rates and to assess the value
      of these data in predicting the risk of surgical morbidity, particularly for
      surgery in eloquent brain regions. METHODS: Neurosurgical outcomes were studied
      for 327 patients who underwent 400 craniotomies for removal of intra-axial
      parenchymal brain neoplasms in a 21-month period. Tumors removed included gliomas
      (206 tumors) and metastases (194 tumors) located both supratentorially (358
      tumors) and infratentorially (42 tumors). RESULTS: The major complication
      incidence was 13%, and the operative mortality rate was 1.7%. The overall
      morbidity rate was 32%, but more types of complications were considered than in
      previous studies. The major neurological morbidity rate was 8.5%. Based on pre-
      versus postoperative (at 4 wk) Karnofsky Performance Scale scores, 9% of patients
      deteriorated neurologically, 32% improved, and 58% showed no change. The median
      postoperative hospital stay was 5 days. Tumors were defined as Grade I, II, or
      III based on their location relative to brain function, and this tumor functional
      grade was the most important variable affecting the incidence of any neurological
      deficit. Patients with tumors in eloquent (Grade III) or near-eloquent (Grade II)
      brain areas incurred more neurological deficits than did patients with tumors in
      noneloquent areas (Grade I). Neither repeat surgery for recurrent disease nor
      extent of surgical resection affected outcome significantly. Although most tumors
      in this study, including those in eloquent regions, were removed by gross total
      resection, this did not lead to more major neurological deficits. Regional
      complications (at the surgical sites) and systemic complications (medical) were
      more prevalent among older patients (age >60 yr) with lower preoperative
      Karnofsky Performance Scale scores (< or = 50) and posterior fossa masses. We
      showed how our data can be used to predict the total risk of surgical morbidity
      for a given patient, to facilitate patient counseling and surgical decision
      making. CONCLUSION: The finding that gross total resections could be performed in
      eloquent brain regions with an acceptable level of neurological impairment
      suggested that the mere presence of a tumor in eloquent brain does not
      automatically contraindicate surgery. Our results have practical risk-predictive
      value, and they should aid in the construction of subsequent outcome studies,
      because we have identified the key areas to monitor.

PMID- 9588550
TI  - Cerebral oxidative metabolism and evoked potential deterioration after severe
      brain injury: new evidence of early posttraumatic ischemia.
AB  - BACKGROUND: We commonly observe progressive deterioration in somatosensory evoked
      potentials (SSEPs) after severe head injury. We had previously been unable to
      relate this deterioration to raised intracranial pressure but had noted a
      relationship with decreasing transcranial oxygen extraction (arteriovenous oxygen
      difference [AVDO2]). The purpose of this study was twofold: to prove the
      hypothesis that deterioration in SSEP values is associated with decreasing AVDO2
      and to test the subsidiary hypotheses that deteriorating SSEPs were the result of
      either ischemia/reperfusion injury or failure of oxygen extraction/utilization.
      METHODS: Monitoring of 97 patients with severe traumatic brain injury (Glasgow
      Coma Scale scores of < or = 8 after resuscitation) included twice daily AVDO2
      measurement and hourly SSEP recording for an average of 5 days. The last 51
      patients also underwent 12-hourly measurement of cerebral blood flow (CBF), with
      calculation of the cerebral metabolic rate of oxygen. Cluster analysis was used
      to classify patients based on initial AVDO2 values and subsequent SSEP trends.
      The time courses of CBF, SSEPs, AVDO2, and cerebral metabolic rate of oxygen were
      examined in the groups defined by the cluster analysis. The clinical outcomes
      considered were survival or nonsurvival and the Glasgow Outcome Scale scores
      obtained at 3 months or more after injury. RESULTS: Cluster analysis confirmed
      the association between high initial AVDO2 values and subsequent SSEP
      deterioration. Patients in this category initially had significantly higher
      AVDO2, lower CBF, and higher cerebral metabolic rates of oxygen but recovered to
      adequate levels within 24 to 36 hours after injury. SSEP values were initially
      identical in the patients with normal AVDO2 values and those with elevated AVDO2
      but differed significantly at 60 hours after injury and beyond. CONCLUSION: The
      findings of increased oxygen utilization and lowered CBF in the patients with
      deteriorating SSEPs strongly imply that early ischemia rather than failure of O2
      extraction or utilization is responsible for the associated SSEP deterioration.
      This issue of defining thresholds for ischemia based on AVDO2 is confounded by
      the dependency of CBF and AVDO2 values on the time after injury.

PMID- 9588551
TI  - Feasibility of the titration method of mild hypothermia in severely head-injured
      patients with intracranial hypertension.
AB  - OBJECTIVE: Clinical strategy to maximize effectiveness and to minimize adverse
      influences remains to be determined for mild hypothermia therapy for traumatic
      brain injury. This study was conducted to evaluate the clinical feasibility of
      the titration method of mild hypothermia in severely head-injured patients in
      whom a reduction in intracranial pressure was regarded as the target effect.
      METHODS: Nine consecutive patients with severe head injury were studied. Patient
      age ranged between 18 and 66 years, Glasgow Coma Scale scores were equal to or
      less than 8, and intracranial pressures were equal to or greater than 20 mm Hg
      despite removal of intracranial hematoma and drugs, including glycerol and
      thiopental. During a maximum of 6 days of hypothermia therapy, jugular venous
      blood or cerebrospinal fluid temperature was titrated to reduce intracranial
      pressure to less than 20 mm Hg by means of repeated intragastric cooling with our
      nasoduodenal tube and surface cooling. The feasibility and the effects on
      systemic complications of this titration method of mild hypothermia were
      evaluated. RESULTS: Intracranial pressure variably decreased from before to 3
      hours after the beginning of all procedures of cooling. The mean intracranial
      pressure significantly decreased from 24 to 15 mm Hg with cooling, while
      temperature reduced an average of 2.0 degrees C. Four patients had systemic
      infection complications. Increased C-reactive protein and decreased platelet
      count were observed in all patients during hypothermia. The incidence of good
      recovery and moderate disability according to the Glasgow Outcome Scale was seven
      of nine patients. CONCLUSION: The titration method of mild hypothermia to control
      intracranial hypertension in severely head-injured patients is clinically
      feasible. However, the method failed to reduce the incidence of infectious and
      hematological complications.

PMID- 9588552
TI  - Comparison of brain temperature with bladder and rectal temperatures in adults
      with severe head injury.
AB  - OBJECTIVE: The purpose of this study was to compare brain temperature (Tbr) with
      conventional indicators of core body temperature (i.e., rectal temperature [Tre]
      and bladder temperature [Tbl]), in adults with severe head injury. METHODS: The
      relationships between Tbr and Tbl and between Tbr and Tre are described in terms
      of differences in temperature in eight patients with severe head injury.
      INSTRUMENTATION: Brain tissue temperature was measured every minute, with a
      thermocouple embedded 2 cm from the tip of a ventriculostomy catheter used to
      measure intracranial pressure. Tbl was measured with a thermistor embedded in a
      bladder catheter, and Tre was measured with a thermistor in a rectal probe.
      RESULTS: Tbr was usually greater than Tbl and Tre. The average difference between
      Tbr and Tbl for each patient ranged from 0.32 to 1.9 degrees C, with standard
      deviations of the difference ranging from 0.30 to 0.80 degrees C. The average
      difference between Tbr and Tre for each patient ranged from 0.1 to 2.0 degrees C,
      with standard deviations of the difference ranging from 0.32 to 1.08 degrees C.
      In the majority of patients, the differences (Tbr - Tbl and Tbr - Tre) were
      greater at temperatures outside of the normal temperature range (Tbr < or =36
      degrees C and >38 degrees C). CONCLUSION: Tbl and Tre often underrepresent Tbr
      after traumatic brain injury, particularly when the patient is hypo- or
      hyperthermic.

PMID- 9588553
TI  - Estimation of vessel flow and diameter during cerebral vasospasm using
      transcranial Doppler indices.
AB  - OBJECTIVE: An important limitation of transcranial Doppler (TCD) ultrasonography
      is its inability to directly measure blood flow or vessel diameter. To extend the
      ability of TCD ultrasonography, indices were derived from an intensity-weighted
      mean of the entire Doppler spectrum. The objective of this article is to test the
      behavior of these indices under conditions of diameter constancy (hyper- and
      hypoventilation) and when vessel diameter decreases (vasospasm). METHODS: A flow
      index (FI) was calculated by averaging several heartbeats of spectral data and
      calculating the first spectral moment. An area index (AI) was defined as the FI
      divided by the mean velocity, motivated by the knowledge that vessel flow is the
      product of vessel diameter and mean velocity. To test the FI and the AI under
      conditions of diameter constancy, middle cerebral artery Doppler signals were
      obtained from 20 patients during conditions of hypercarbia, hypocarbia, and
      normocarbia. To test the ability of these indices to evaluate a decrease in
      vessel diameter, signals from 41 sites on 23 arteries were obtained from patients
      who underwent both TCD and angiographic studies on two separate occasions after
      the occurrence of subarachnoid hemorrhage. The changes in the AI were compared
      with the arterial diameters measured from angiograms. RESULTS: The FI was
      proportional to the mean velocity in the cohort of healthy patients (r=0.97). The
      AI changed by less than 3% in the same cohort. The AI predicted the direction of
      the diameter change in all vessels showing angiographic changes in area. Changes
      in the AI and the measured angiographic changes in cross-sectional areas were
      correlated (overall, r=0.90; with two outlines removed, r=0.86). CONCLUSION: This
      variant of the intensity-weighted mean predicts changes in vessel cross-sectional
      area under conditions of changes in CO2 and cerebral vasospasm. This preliminary
      study suggests that careful use of this tool may provide accurate evaluation of
      cerebral blood flow through the large vessels and quantitative changes in
      diameter, which occur frequently after subarachnoid hemorrhage.

PMID- 9588554
TI  - Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and
      other means.
AB  - OBJECTIVE: This article reviews historical aspects of the blood-brain barrier
      (BBB) and recent advances in mechanisms to deliver therapeutic agents across the
      BBB for the treatment of intracerebral tumors and other neurological diseases.
      METHODS: The development of the osmotic BBB disruption procedure as a clinically
      useful technique is described. Osmotic BBB disruption is contrasted with
      alternative methods for opening or bypassing the BBB, including pharmacological
      modification of the BBB with bradykinin and direct intracerebral infusion.
      RESULTS: Laboratory studies have played a fundamental role in advancing our
      understanding of the BBB and delivery of agents to brain. Preclinical animal
      studies will continue to serve an integral function in our efforts to improve the
      diagnosis and treatment of a number of neurological disorders. Techniques
      involving the modification of the BBB and/or blood-tumor barrier to increase
      delivery of therapeutic agents have been advanced to clinical trials in patients
      with brain tumors with very favorable results. CONCLUSION: Improving delivery of
      agents to the brain will play a major role in the therapeutic outcome of brain
      neoplasms. As techniques for gene therapy are advanced, manipulation of the BBB
      also may be important in the treatment of central nervous system genetic
      disorders.

PMID- 9588555
TI  - Surgical treatment of cerebrospinal fluid fistulae involving lateral extension of
      the sphenoid sinus.
AB  - OBJECTIVE AND IMPORTANCE: Four cases of spontaneous cerebrospinal fluid
      rhinorrhea caused by communication between the subarachnoid space of the middle
      cranial fossa and a lateral extension of the sphenoid sinus are presented. The
      cause and management of this unique type of cranial base defect are discussed.
      CLINICAL PRESENTATION: During the past 10 years, four patients referred to our
      institution with atraumatic cerebrospinal fluid fistulae were observed to have
      temporal encephaloceles (encephalomeningoceles) traversing the floor of the
      middle cranial fossa. Three of the patients had previously undergone unsuccessful
      transnasal attempts to repair their fistulae by obliteration of the sphenoid
      sinus. The fourth patient presented before undergoing any treatment. No patient
      had associated hydrocephalus or tumor. Preoperative computed tomographic
      cisternograms revealed that all fistulae involved a lateral extension of the
      sphenoid sinus into the floor of the middle cranial fossa. INTERVENTION: After
      definitive localization, each patient was operated on transcranially through an
      anterior middle cranial fossa approach with extradural and/or intradural
      exploration. The associated temporal encephalocele was amputated or disconnected,
      and the dehiscent dura and middle cranial fossa floor defect were oversewn and
      packed with autogenous tissue, respectively. CONCLUSION: The surgical treatment
      of cerebrospinal fluid rhinorrhea secondary to middle fossa encephalocele
      associated with lateral extension of the sphenoidal sinus differs from the
      surgical strategy for more medial sphenoidal fistulae. Fistulae involving a
      lateral extension of the sphenoid sinus require a transcranial approach for
      direct visualization and obliteration of the defect, whereas fistulae involving
      the central portion of the sinus may be successfully obliterated
      transsphenoidally.

PMID- 9588556
TI  - Cerebellar epilepsy.

PMID- 9588557
TI  - Excision repair cross-complementing rodent repair deficiency gene 2 expression
      and chloroethylnitrosourea resistance in human glioma cell lines.
AB  - OBJECTIVE: Nitrosoureas are the standard chemotherapeutic agents for malignant
      brain tumors. However, their anticancer effects are limited because many tumors
      are resistant to these agents. Nucleotide excision repair can repair bulky
      deoxyribonucleic acid adducts, including deoxyribonucleic acid damage induced by
      ultraviolet light and some chemotherapeutic agents, and may be implicated in
      nitrosoureas resistance. In this study, we compared excision repair cross
      complementing rodent repair deficiency Gene 2 (ERCC2), an important component of
      the nucleotide excision repair system, with 1 ,3-bis-(2-chloroethyl)-1
      nitrosourea or (2-chloroethyl)-3-sarcosinamide-1-nitrosourea resistance in human
      glioma cell lines. METHODS: ERCC2 expression was evaluated by using established
      quantitative reverse-transcription polymerase chain reaction. 1,3-Bis-(2
      chloroethyl)-1-nitrosourea and (2-chloroethyl)-3-sarcosinamide-1-nitrosourea
      cytotoxicity were determined by a modification of the sulforhodamine B
      colorimetric anticancer drug screening assay. RESULTS: A significant correlation
      between ERCC2 expression and 1 ,3-bis-(2-chloroethyl)-1-nitrosourea or (2
      chloroethyl)-3-sarcosinamide-1-nitrosourea cytotoxicity was determined (r=0.737,
      P=0.0226 and r=0.789, P=0.0113, respectively). CONCLUSION: Our results suggest
      that nucleotide excision repair, specifically ERCC2, may play an important role
      in nitrosoureas drug resistance in human gliomas.

PMID- 9588559
TI  - Neurotransmitter and amino acid analysis and ultrastructural observations of
      fetal brain cortex transplantation to adult rat brain under the effect of
      dexamethasone.
AB  - OBJECTIVE: To conduct an investigation of fetal cortical tissue graft survival
      using transmission electron microscopy and analyzing neurotransmitters and amino
      acids and their function, with special reference to the effect of dexamethasone.
      METHODS: Transplantation of fetal cortical brain tissue to 100 adult Wistar
      albino rats weighing 170 to 220 g was performed. The rats were divided into three
      groups. Only transplantation of fetal cortical brain tissue was performed in the
      first group (n=36). In the second group (n=48), dexamethasone was administered in
      addition to fetal cortical tissue transplantation. The third group (n=16) was
      used as the surgical control group. The rats were allowed to live for 6 weeks and
      were then decapitated. The grafts were examined by electron microscopy.
      Additionally, quantitative analyses of the neurotransmitters and amino acids of
      the grafts were conducted using high-pressure liquid chromatography. RESULTS:
      Electron microscopic observations revealed that the grafts were still surviving
      at the end of the 6th week in both groups. However, in the group that received
      dexamethasone, neurons and their organelles were better developed than in the
      group that did not receive dexamethasone. Concommitantly, results of quantitative
      analysis in the dexamethasone group revealed statistically extremely significant
      higher amino acid values for glutamic acid, aspartic acid, beta-alanine, and
      lysine and significantly higher values for gamma-aminobutyric acid, glutamine,
      glycine, and serine when compared to the nondexamethasone group. CONCLUSION:
      Dexamethasone is effective in increasing the survival and in developing the
      ultrastructural and functional outcome of transplanted neurons in fetal grafts.

PMID- 9588558
TI  - Telomerase activity in human gliomas.
AB  - OBJECTIVE: Telomerase activity, which is undetectable in most mature normal
      tissues, has been identified in many types of human cancers, including
      neuroblastomas and oligodendrogliomas. These findings suggest that a novel
      mechanism in addition to activation of oncogenes and inactivation of tumor
      suppressor genes may play an important role in tumorigenesis. The goal of the
      present study was to assess and correlate the telomerase activity in astrocytic
      gliomas of different grades. METHODS: Telomere repeat amplification protocol and
      Southern blot hybridization with telomere-specific probes were used to detect
      telomerase activity and to measure terminal restriction fragment length,
      respectively. RESULTS: Telomerase activity was detected in 3 of 9 (33%) low-grade
      astrocytomas (World Health Organization Grade II), 5 of 11 (45%) anaplastic
      astrocytomas (World Health Organization Grade III), 36 of 41 (89%) glioblastomas
      multiforme (World Health Organization Grade IV), 3 of 4 (75%) oligodendrogliomas,
      and none of 4 normal brain specimens. CONCLUSION: We demonstrated that telomerase
      activity is absent in normal brain tissues while present in most glioma samples
      (72%). The frequency of such activity increases with malignancy. These results
      suggest that telomerase activity may be used as a tumor marker and that the
      activation of telomerase may correlate with initiation and malignant progression
      of astrocytic tumors.

PMID- 9588560
TI  - Partial thrombosis of canine carotid bifurcation aneurysms with cellulose acetate
      polymer.
AB  - OBJECTIVE: To investigate the usefulness of a cellulose acetate polymer (CAP)
      solution for partial thrombosis of aneurysms. METHODS: We created 14 canine
      cervical carotid bifurcation aneurysms, 11 of which were subsequently thrombosed
      partially with CAP solution. We then conducted angiographic and histological
      investigations. RESULTS: Nine aneurysms were thrombosed 50 to 70% by volume,
      although a significant crescent crevice between the aneurysmal sac and the CAP
      mass was left in four of the aneurysms. In the remaining two aneurysms in which a
      crescent crevice had been seen in the initial stage of CAP injection, 80% and
      more than 95% thrombosis were needed to occlude the crevice, respectively. Follow
      up angiograms of the seven aneurysms with no crescent crevice revealed no shifts
      of position of the CAP mass toward the bottom of the aneurysm sac, but slight
      ballooning of the remnants was observed in two of them. The angiograms of the
      other four aneurysms with significant crescent crevices demonstrated rupture with
      a massive hematoma in one and shifts of the CAP mass with marked enlargement of
      remnants in three. Histologically, the seven aneurysms with no enlarged remnants
      had newly developed membranes consisting of endothelium, infiltrated spindle
      shaped cells, collagen, and elastic fibers. In contrast, in the three markedly
      enlarged aneurysms, there were only recent clots between the CAP mass and the
      aneurysm lumen and no development of endothelium. CONCLUSION: Partial thrombosis
      with CAP solution is useful to keep aneurysms in a stable configuration, unless a
      crescent crevice has been left.

PMID- 9588562
TI  - Hemangioendothelioma of the cavernous sinus: case report.
AB  - OBJECTIVE AND IMPORTANCE: Hemangioendothelioma is an uncommon vascular neoplasm,
      and its intracranial occurrence is extremely rare. The occurrence of such a tumor
      within the cavernous sinus has not been reported previously. CLINICAL
      PRESENTATION: We report a 36-year-old woman who presented with right-sided retro
      orbital pain and diplopia caused by a right sixth nerve paresis. Magnetic
      resonance imaging revealed a lesion within the right inferior cavernous sinus.
      INTERVENTION: The tumor was excised completely via an orbitozygomatic approach.
      CONCLUSION: Hemangioendothelioma is a rare, indolent vascular tumor, and its
      characteristics are reviewed. The need for complete excision is emphasized, and
      the advantages of the orbitozygomatic approach for the removal of tumors of the
      cavernous sinus is discussed.

PMID- 9588561
TI  - Diseases of the skull in pre-Columbian South American mummies.
AB  - OBJECTIVE: The majority of paleopathological investigations focus on the study of
      the skull. This is because the skull is the most frequently preserved part of the
      human body recovered from archaeological excavations. From studying the skull, a
      variety of information can be obtained regarding the individual, such as sex,
      age, nutritional status, and other disease processes, if present. METHODS: This
      study represents the examination of more than 700 human skulls recovered from
      archaeological excavations from the Andean region of southern Peru and northern
      Chile and dating back more than 8000 years. RESULTS: A variety of skull
      abnormalities were encountered. The nonmetric variables of Huschke's foramina and
      palatine tori were common. Cranial deformation was observed in more than 85% of
      the cases. There were two cases of sagittal synostosis. Iron deficiency anemia
      resulting in porotic hyperostosis of the skull was evident in certain cultures.
      Exostoses of the external auditory canal resulting from chronic otitis was
      evident only among coastal populations. One skull demonstrated a periostitis
      consistent with Treponema infection. Trephination was encountered only in the
      skulls from Peru. Fifty-four cases of skull fractures were observed, half of
      which showed evidence of healing. Finally, only two cases of neoplastic skull
      lesions were encountered. CONCLUSION: The study of the human skull alone provides
      a large amount of information regarding the health and diseases of ancient
      populations.

PMID- 9588563
TI  - Direct revascularization to the anterior cerebral artery territory in patients
      with moyamoya disease: report of five cases.
AB  - OBJECTIVE: In some patients with moyamoya disease, the development of spontaneous
      leptomeningeal collateral channels between the anterior cerebral artery (ACA) and
      other major arteries is poor. These patients require revascularization not only
      to the territory of the middle cerebral artery (MCA) but also to that of the ACA.
      For reliable revascularization to the ACA territory, we performed superficial
      temporal artery (STA)-ACA direct anastomosis in 5 of 58 patients with moyamoya
      disease who underwent cerebral revascularization at our institute during the last
      8 years. METHODS: Because two patients presented with ischemic symptoms
      corresponding to the ACA territory after the ipsilateral STA-MCA anastomosis, we
      subsequently performed STA-ACA anastomosis. In three patients in whom
      hypoperfusion in the ACA territory was suspected based on preoperative angiograms
      and/or stimulated cerebral blood flow studies, we performed STA-ACA and STA-MCA
      anastomoses during a single operative procedure. After paramedian frontal
      craniotomy (diameter, approximately 5 cm), STA-ACA anastomosis was performed at
      the convexity, using a cortical branch of the ACA as a recipient. An interposed
      STA graft was used in four patients; all of the grafts were shorter than 4 cm.
      RESULTS: Bypass flow was satisfactory in four patients. One patient who underwent
      simultaneous STA-ACA and STA-MCA anastomoses had poor bypass flow, probably
      caused by spontaneous leptomeningeal collateral channels between the ACA and MCA.
      No patient had an ischemic attack after surgery. CONCLUSION: Our method using a
      cortical branch of the ACA as a recipient and a branch of the STA for the
      interposed graft can be performed at the convexity and much more easily than in a
      deep operative field. Our experience with STA-ACA anastomosis indicates that this
      procedure is effective for revascularization of the ACA territory in patients
      with moyamoya disease.

PMID- 9588564
TI  - Endovascular treatment of traumatic dural sinus thrombosis: case report.
AB  - OBJECTIVE: Dural sinus thrombosis has rarely been associated with closed head
      injury. We present a unique case involving the use of endovascular thrombolysis
      in the treatment of traumatic dural sinus thrombosis, which has not been
      reported. CLINICAL PRESENTATION: A 20-year-old male patient suffered a severe
      closed head injury while skiing. He developed refractory elevated intracranial
      pressure requiring barbiturate coma. Angiography demonstrated thrombosis of the
      dominant right transverse and sigmoid sinuses, with partial thrombosis of the
      superior sagittal sinus. Urokinase was administered via a microcatheter within
      the thrombus as a bolus of 250,000 units and then as a continuous infusion of
      60,000 to 100,000 units per hour for 48 hours. The patient was maintained in a
      barbiturate coma and heparinized. Serial angiography was performed to assess the
      sinus patency and efficacy of thrombolysis. RESULTS: After 48 hours of
      thrombolysis, angiography demonstrated normal patency of the superior sagittal,
      right transverse, and right sigmoid sinuses. The intracranial pressure decreased
      after thrombolysis and was manageable with conventional techniques. Within 48
      hours of the completed thrombolysis, the barbiturates were withdrawn and the
      patient's neurological status rapidly improved until the time of discharge 2
      weeks later. DISCUSSION AND CONCLUSION: This case documents a rare instance of
      traumatic dural sinus thrombosis resulting from a closed head injury. In
      addition, endovascular thrombolysis resulted in subsequent opening of the dural
      sinuses and effective intracranial pressure management, despite the presence of a
      hemorrhagic contusion. Heparin was effective in maintaining sinus patency and was
      used safely in conjunction with urokinase in this setting of head injury.

PMID- 9588565
TI  - Chiari malformation associated with vitamin D-resistant rickets: case report.
AB  - INTRODUCTION: Craniocervical junction abnormalities have a wide range of origins,
      from rare congenital conditions to common arthritic processes. We present a rare
      case of foramen magnum stenosis with Chiari I malformation and associated
      syringomyelia, which resulted from vitamin D-resistant hypophosphatemic rickets.
      METHODS: This 12-year-old male patient had a history of vitamin D-resistant
      rickets, and he presented with a 1-year history of increasing upper extremity
      weakness and sharp pain in the left shoulder and arm. Magnetic resonance imaging
      of his spine showed a large syrinx from C2 to T7, with significant foramen magnum
      stenosis and a Chiari Type I malformation. RESULTS: The patient underwent
      craniocervical decompression, consisting of a suboccipital craniectomy and C1
      laminectomy with duraplasty. A pathological evaluation of bone yielded no
      diagnostic abnormality. Postoperative magnetic resonance imaging showed
      significant reduction in the diameter of the cervical thoracic spinal cord syrinx
      3 months after surgery. The patient's pain and sensation in his left arm had not
      improved by that time, and he still had some diffuse weakness in his arms. Two
      years later, he had persistent left shoulder girdle pain and his syrinx had
      collapsed, except for a small residual from T2 to T6. DISCUSSION AND CONCLUSION:
      The bone disease of vitamin D-resistant rickets can involve the base of the
      cranium, precipitating the development of the Chiari malformation and associated
      syringomyelia. We review the association between rickets and Chiari malformation
      and discuss the management of these patients.

PMID- 9588566
TI  - High serum levels of somatomedin-C and diabetes mellitus caused by obstructive
      hydrocephalus: case report.
AB  - OBJECTIVE AND IMPORTANCE: This case demonstrates a relationship between
      hydrocephalus with a huge diverticulum of the third ventricle and high serum
      levels of somatomedin-C. Somatomedin-C levels become high when the secretion of
      growth hormone from the adenohypophysis increases, and previous reports state
      that hydrocephalus decreases the secretion of growth hormone. CLINICAL
      PRESENTATION: The patient suffered from diabetes mellitus and obesity, and serum
      somatomedin-C levels were high. A pituitary adenoma or ectopic growth hormone
      producing tumor was suspected. Magnetic resonance imaging did not reveal either
      of these abnormalities but indicated hydrocephalus with a diverticulum of the
      third ventricle. INTERVENTION: After ventriculoperitoneal shunt placement, the
      blood glucose and serum somatomedin-C levels of the patient decreased toward
      normal. Six months later, the shunt tube became obstructed and serum somatomedin
      levels increased. The levels decreased again after shunt revision. CONCLUSION: To
      our knowledge, this is the first published report of obstructive hydrocephalus
      with a diverticulum of the third ventricle compressing the hypothalamus and
      increasing the serum levels of somatomedin-C.

PMID- 9588567
TI  - Spinal cord compression by catheter granulomas in high-dose intrathecal morphine
      therapy: case report.
AB  - OBJECTIVE AND IMPORTANCE: The use of chronic intrathecal morphine for the
      treatment of intractable, nonmalignant pain is becoming more prevalent. A rare
      but devastating complication of this therapy is the development of spinal cord
      compression secondary to the formation of intrathecal granulomas. CLINICAL
      PRESENTATION: We report three cases of intrathecal granuloma formation in the
      thoracic subarachnoid space, associated with intrathecal morphine pumps. These
      three patients were receiving high doses of morphine to control their pain (25
      mg/d, 28 mg/d, and 45 mg/d, respectively) when they presented with signs and
      symptoms of thoracic spinal cord compression. Myelography and postmyelographic
      computed tomography of the spine revealed masses causing spinal cord compression.
      INTERVENTION: Two patients underwent thoracic laminectomies for resection of
      these masses, and the other patient had the intrathecal catheter removed. A
      pathological examination revealed sterile granulomas in the resected masses.
      CONCLUSION: Intrathecal granulomas are likely to occur with increasing frequency
      as the use of chronic intrathecal morphine delivery increases in patients with
      nonmalignant pain. The cause of intrathecal granulomas is unknown, although it is
      likely that morphine plays a major role in their formation. We think that those
      patients receiving high doses of morphine are at greater risk for developing this
      complication.

PMID- 9588568
TI  - A newly developed shunt system for carotid surgery: T-shaped silicone shunt tubes
      and clamping devices: technical note.
AB  - BACKGROUND: Although the use of a shunt during carotid endarterectomy has been
      controversial, a convenient shunt system is still required. METHODS: We have
      devised an intraluminal shunt system, T-shaped silicone shunt tubes, and clamping
      devices for carotid surgery. The tube has enough pliability and length to be used
      in a looped or U-shaped mode and constructs a T-shape with a side arm available
      for monitoring blood pressure in the shunt system. Clamping devices, such as
      modified Sugita ring clips and encircle type bulldog clamps, make it possible to
      hold the tube by a simple maneuver and to minimize the intimal damage. RESULTS:
      This shunt system has been used in 170 carotid endarterectomies and other 10
      carotid surgical operations, and the mortality and morbidity rates were 0% and
      2.4%, respectively. CONCLUSION: This shunt system can be safely and easily used
      for cervical carotid surgery.

PMID- 9588570
TI  - Progressive intracranial aneurysmal disease in a child with progressive
      hemifacial atrophy (Parry-Romberg disease): case report.

PMID- 9588571
TI  - Vagus nerve stimulation activates central nervous system structures in epileptic
      patients during PET H2(15)O blood flow imaging.

PMID- 9588572
TI  - Optic nerve compression by a dolichoectatic internal carotid artery: case report.

PMID- 9588573
TI  - Intrasellar pituitary gangliocyto-adenoma presenting with acromegaly: case
      report.

PMID- 9588574
TI  - A pitfall in the surgery of a recurrent aneurysm after coil embolization and its
      histological observation: technical case report.

PMID- 9588575
TI  - The in vivo metabolic pattern of low-grade brain gliomas: a positron emission
      tomographic study using f-18-fluorodeoxyglucose and c-11-L-methylmethionine.

PMID- 9588576
TI  - The International Society for Heart and Lung Transplantation: a focus on our
      mission.

PMID- 9588577
TI  - The inhibitory effects of pravastatin on natural killer cell activity in vivo and
      on cytotoxic T lymphocyte activity in vitro.
AB  - BACKGROUND: We have reported that heart transplant recipients treated with
      pravastatin demonstrate decreases in the incidence of clinically severe acute
      rejection episodes, the incidence and progression of transplant coronary
      vasculopathy, and natural killer cytotoxicity. These patients also exhibited a
      significant improvement in 1-year allograft survival. Because of these clinical
      findings suggesting an immunosuppressive effect of pravastatin unique to
      transplant recipients and the unclear role of natural killer cells in allograft
      rejection, we postulated that pravastatin may exert its immunomodulatory effect
      by acting with cyclosporine to alter T lymphocyte function. METHODS: Twenty
      patients randomized into an ongoing trial of pravastatin after heart
      transplantation were monitored serially for natural killer cell cytotoxicity. In
      a separate experiment, lymphocytes isolated from normal volunteers were treated
      with various combinations of pravastatin and cyclosporine and tested for
      cytotoxic T lymphocyte toxicity in a one-way mixed lymphocyte reaction. RESULTS:
      Pravastatin-treated heart transplant recipients exhibited a decrease in natural
      killer cell cytotoxicity (9.8% mean natural killer cell cytotoxicity vs 22.1% in
      the control group, p < 0.01). In the one-way mixed lymphocyte reaction with blood
      obtained from control subjects, there was a synergistic inhibition of cytotoxic T
      lymphocyte activity when the cells were cultured in a combination of pravastatin
      and cyclosporine (20.3% mean cytotoxicity of target cells vs 41.4% in the control
      group, p < 0.01). CONCLUSIONS: Pravastatin exerts an immunosuppressive effect in
      heart transplant recipients as expressed by a reduction in rejection and natural
      killer cell cytotoxicity. Pravastatin and cyclosporine act synergistically to
      reduce cytotoxic T lymphocyte activity. This synergistic effect of pravastatin
      and cyclosporine may explain why this immunosuppressive effect is unique to
      transplant recipients.

PMID- 9588578
TI  - Afferent reinnervation after lung transplantation in the rat.
AB  - Denervation at lung transplantation results in loss of cough reflex and
      attenuated local defense mechanisms, accounting for increased incidence and
      severity of infection after lung transplantation. We studied the presence or
      absence of spontaneous afferent reinnervation in rats at various intervals after
      orthotopic left pulmonary isografting (n = 52). Normal rats (n = 21) and rats
      undergoing left hilar stripping (n = 14) served as control subjects. Afferent
      reinnervation was tested physiologically by reflex bradycardia in response to
      intravenous infusion of capsaicin (30 microg/kg), an extract of paprika
      stimulating pulmonary C-fibers. Injection of capsaicin was repeated before and
      after right pulmonary artery occlusion to divert all pulmonary blood flow to the
      left lung or isograft. Whereas rats early after surgical denervation lost the
      reflex after right pulmonary artery occlusion, rats examined 8 months or longer
      after surgery showed potent reflex bradycardia in response to capsaicin, as did
      the control rats. Immunohistochemical staining for sensory neuron-specific
      substances, such as calcitonin gene-related peptide and substance P, were
      identified only in the right native lung and left pulmonary isografts 2 months or
      longer after transplantation. Fluorogold was found only in the ipsilateral nodose
      ganglion after left lung intrapleural injection of the neuron-specific tracer in
      rats 8 months or longer after denervation. These experiments provide
      physiological, morphologic, and neurologic evidence suggesting that afferent lung
      innervation, abolished early after transplantation, is spontaneously
      reestablished and functioning in the ipsilateral vagus nerve by 8 months after
      pulmonary isografting in the rat.

PMID- 9588579
TI  - Prevention of ischemically induced neointimal hyperplasia using ex vivo antisense
      oligodeoxynucleotides.
AB  - BACKGROUND: Chronic graft vascular disease in cardiac allografts results from
      coronary artery neointimal formation. Vascular ischemia has been shown to provoke
      the development of neointimal hyperplasia through endothelial damage. We used a
      rodent model of neointimal formation to test the in vivo effects of antisense
      oligodeoxynucleotides (AS ODN) specifically designed to block this process.
      METHODS: Aortas from ACI rats were mock transfected or transfected with 18 base
      pair AS ODNs against the 5' start codon region of both CDC2 kinase, and
      proliferating cell nuclear antigen (PCNA) mRNA. Transfection was accomplished by
      placing the aorta in ODN solution (transfected group, 40 micromol/L of each
      sequence) or saline solution alone (mock-transfected group) and exposing to
      hydrostatic pressure (2 atm) for 24 hours at 4 degrees C. Vessels were then
      interposition-grafted into the abdominal aorta of untreated isogenic recipients
      and procured on postoperative days (POD) 1, 6, and 14. RESULTS: Nuclear
      localization of fluorescein isothiocyanate ODN was observed in 81%+/-3% of medial
      smooth muscle cells at 24 hours after interposition grafting and reperfusion.
      Efficacy of AS ODNs at blocking CDC2 kinase and PCNA was verified on POD 6 by
      enzyme-linked immunosorbent assay. This blockade significantly reduced
      ischemically induced vascular narrowing on POD 14 as assessed by use of
      computerized image analysis (3.85%+/-2.45% luminal narrowing for transfected vs
      7.11%+/-2.03% for control subjects, p < 0.03). CONCLUSIONS: Our data show the
      efficacy of AS ODN at blocking rat PCNA and CDC2 kinase up-regulation provoked by
      ischemia. This ex vivo approach had beneficial effects against vascular narrowing
      in a rodent model of ischemically induced neointimal hyperplasia, an antigen
      independent factor important in the development of subsequent chronic graft
      vascular disease.

PMID- 9588580
TI  - Circulating tumor necrosis factor-alpha levels in chronic heart failure: relation
      to its soluble receptor II, interleukin-6, and neurohumoral variables.
AB  - The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)
      are increased in the circulation of patients with chronic heart failure. However,
      their correlation with left ventricular dysfunction has not yet been thoroughly
      evaluated, and their interrelation with other neurohumoral systems, such as the
      adrenergic system and endothelin, is unclear. Therefore TNF-alpha, its soluble
      receptor II, IL-6, big endothelin, and noradrenaline levels were simultaneously
      measured in venous blood from 65 patients with heart failure in New York Heart
      Association (NYHA) class II to IV during therapy with digitalis, furosemide, and
      enalapril. TNF-alpha plasma levels were 3.2+/-0.2 SEM pg/ml in 38 patients in
      NYHA function class II, 4.0+/-0.3 SEM pg/ml in 16 patients in NYHA function class
      III, and 5.3+/-0.9 SEM pg/ml in 11 patients in NYHA function class IV (p < 0.001
      vs NYHA function class II). IL-6 plasma levels were 3.1+/-0.6 SEM pg/ml in 38
      patients in NYHA function class II, 5.2+/-0.8 SEM pg/ml in 16 patients in NYHA
      function class III, and 13.3+/-3.9 SEM pg/ml in 11 patients in NYHA function
      class IV (p < 0.0001 vs NYHA function class II andp < 0.0001 vs NYHA class III).
      Thus both cytokines increased with increasing severity of heart failure, but only
      IL-6 plasma levels were different in patients in the more severe function
      classes. TNF-alpha correlated closely with TNF soluble receptor II (r = 0.8, p <
      0.0001) and modestly with serum creatinine (r = 0.6, p < 0.0001), whereas IL-6
      plasma levels were not statistically related to kidney function. Significant
      modest correlations were also found among TNF-alpha and IL-6 (r = 0.3, p < 0.01),
      big endothelin (r = 0.3, p < 0.01), and noradrenaline levels (r = 0.4, <0.001).
      This study supports the hypothesis that in heart failure both cytokines, TNF
      alpha, and IL-6, as well as neurohumoral factors, play a role in the clinical
      progression of the disease. Thereby levels of TNF-alpha but not IL-6 seem to be
      related to concomitant kidney dysfunction.

PMID- 9588581
TI  - The nature of acute rejection is associated with development of graft vascular
      disease after clinical heart transplantation.
AB  - BACKGROUND: To determine mechanisms that trigger graft vascular disease (GVD)
      after heart transplantation, we studied parameters that reflect both early and
      late intragraft allogeneic reactions. METHOD: With reverse transcriptase
      polymerase chain reaction analysis, mRNA expression of interleukin-2 (IL-2),
      interleukin-4, interleukin-6, interleukin-10, interferon-gamma, platelet-derived
      growth factor-alpha, and transforming growth factor-beta was measured in
      endomyocardial biopsy (EMB) specimens obtained from 34 recipients during the
      first acute rejection episode (n = 29) or at a comparable time after
      transplantation for patients without rejection (n = 5) and at time of assessment
      of GVD by coronary angiography at 1 year (n = 34). RESULTS: At the time of
      assessment of GVD, mRNA expression of IL-2, interleukin-4, and interleukin-6 were
      barely detectable, whereas messenger coding for interferon-gamma, interleukin-10,
      transforming growth factor-beta, and platelet-derived growth factor-alpha genes
      were constitutively expressed. Moreover, intragraft mRNA patterns of cytokines
      and growth factors between patients with GVD (n = 17) or without GVD (n = 17)
      were comparable. In contrast, during the first acute rejection episode a
      completely different pattern was found. Development of GVD was associated with IL
      2 mRNA expression and not with the other cytokines analyzed. IL-2 mRNA was
      present in 77% of rejection EMB specimens obtained from patients with GVD versus
      33% of the EMB specimens obtained from patients without GVD (p = 0.03) and not
      detectable in EMB specimens obtained from patients with no rejection. Also
      nonimmunologic risk factors such as longer ischemia time (median 193 vs 141
      minutes; p = 0.002) and higher donor age (median 32 vs 23 years; p = 0.02) were
      associated with GVD. But no relation was found between these nonimmunologic risk
      factors and IL-2-positive acute rejections. CONCLUSIONS: Nonspecific risk factors
      and IL-2-positive rejections may independently trigger GVD after clinical heart
      transplantation.

PMID- 9588582
TI  - Morbidity, functional status, and immunosuppressive therapy after heart
      transplantation: an analysis of the joint International Society for Heart and
      Lung Transplantation/United Network for Organ Sharing Thoracic Registry.
AB  - BACKGROUND: The morbidity and mortality studies on heart transplantation to date
      have come from single-center or multicenter studies that often have required
      collection of data over periods of time greater than a year. Data are now
      available from the International Society for Heart and Lung
      Transplantation/United Network for Organ Sharing (ISHLT/UNOS) Thoracic Registry
      from all centers in the United States performing heart transplantation, which
      allows analysis of morbidity and mortality rates on an annual basis. METHODS: All
      transplantation centers in the United States are now required to submit
      registration (at the time of transplantation) and 1-year follow-up clinical data
      on all heart transplant recipients to the ISHLT/UNOS Thoracic Registry. Data
      forms were submitted to the Registry regarding pretransplantation diagnoses,
      causes of death, rehospitalization, functional and work status at 1 year,
      immunosuppressive therapy, and the development of complications such as
      hypertension, hyperlipidemia, renal insufficiency, diabetes, and malignancy. This
      study is an analysis of this database for the period of April 1, 1994, through
      March 31, 1995, examining specifically morbidity, functional status, and other
      clinical events occurring during the period after the initial hospitalization and
      up to the first-year follow-up. The study cohort consisted of the 1853 patients
      who survived the initial hospitalization and for whom matching registration and 1
      year follow-up forms were available. RESULTS: Rehospitalization during the first
      year after the initial admission was required by more than 40% of survivors, and
      at least one third of these required admission to the intensive care unit.
      Infection and rejection were the most common reasons for rehospitalization, each
      accounting for about 20%. Complications during the first year occurring in 10% or
      more of survivors included hypertension, diabetes, renal dysfunction, and
      hyperlipidemia. Less common complications included symptomatic bone disease,
      chronic liver disease, cataracts, stroke, and malignancy. Allograft function was
      excellent among survivors at 1 year, with a mean ejection fraction of 57.4% and
      less than 7% of patients requiring pacemaker therapy or having development of
      coronary artery disease. Eighty-three percent of survivors reported no functional
      limitations, but only 27% were working full-time. Eighty-nine percent of
      survivors were receiving prednisone at their 1-year follow-up. CONCLUSION:
      Clinical data are now available from the ISHLT/UNOS Thoracic Registry on the
      basis of the initial registration and 1-year follow-up of all patients undergoing
      heart transplantation in the United States. Analysis of these data from April 1,
      1994, through March 31, 1995, demonstrates that the first year after the initial
      hospitalization for heart transplantation is a period of significant morbidity
      and frequent rehospitalization but excellent survival. In spite of a high level
      of functional capacity at 1-year follow-up, only a minority of patients return to
      work. The ISHLT/UNOS Thoracic Registry can now serve as a valid source of data
      for future analysis of trends in heart transplantation in the United States.

PMID- 9588583
TI  - Patient compliance at one year and two years after heart transplantation.
AB  - BACKGROUND: The purpose of this report is to determine the extent of difficulty
      following and self-reported compliance with prescribed activities at 1 year after
      heart transplantation, identify postoperative predictors of compliance at 1 year
      after transplantation, and compare difficulty following and compliance with the
      therapeutic regimen at 1 year versus 2 years after transplantation. METHODS: Data
      were collected from a nonrandom sample of 120 adult patients 1 year after heart
      transplantation and 76 of 120 patients 2 years after transplantation. Patients
      were 83% male, mean age 54 years, 86% were married, 28% were employed, and 91%
      were in NYHA class I at 1 year after transplantation. Data were collected from
      the Assessment of Problems with the Heart Transplant Regimen, Quality of Life
      Index, Heart Transplant Symptom Checklist, Sickness Impact Profile, Heart
      Transplant Stressor Scale, Jalowiec Coping Scale, Social Support Index, Heart
      Transplant Intervention Scale, Rating Question Form, and chart review. Data were
      analyzed via frequencies, multiple regression, paired t-tests, and the Wilcoxon
      matched-pairs signed-ranks test. RESULTS: At both 1 year and 2 years after
      transplantation, patients had almost no difficulty following the heart
      transplantation regimen and complied almost all of the time with taking
      medications, attending clinic, and completing scheduled tests. Patients complied
      less with following a diet, exercising, and taking their vital signs. Predictors
      of compliance at 1 year after heart transplantation differed by prescribed
      activity, explaining from 13% to 52% of variance (p < or = 0.0001). CONCLUSIONS:
      These findings indicate the need to continue the study of heart transplant
      recipient compliance longitudinally for individual prescribed activities and
      provide evidence and direction for the development of interventions to enhance
      patient compliance.

PMID- 9588584
TI  - Cardiac troponin T: a noninvasive marker for heart transplant rejection?
AB  - BACKGROUND: Diagnosis of acute rejection remains a major concern in heart
      transplant recipients. Currently, endomyocardial biopsy is the gold standard for
      detecting rejection. Given the risks and cost of endomyocardial biopsy, a
      noninvasive marker for rejection would be ideal. Cardiac troponin T (cTnT) is an
      established marker of myocyte damage, and a rat transplantation model of heart
      transplant rejection has suggested that cTnT may be of value in detecting
      rejection. METHODS: The cTnT levels were measured in 90 transplant recipients (67
      men and 23 women) at the time of endomyocardial biopsy. There were a total of 256
      cTnT levels and 256 biopsy samples. The cTnT levels were compared by use of
      International Society of Heart and Lung Transplantation rejection grades.
      RESULTS: Only one of the 12 grade 3 biopsy specimens had a corresponding elevated
      cTnT level. Of the 29 biopsy specimens with myocyte necrosis (grade 2 or grade
      3), three had a corresponding elevated cTnT. The cTnT levels were elevated during
      the first 1 to 2 months after transplantation. There was no correlation between
      ischemic time and cTnT levels. CONCLUSION: CTnT is an insensitive marker of acute
      rejection, both early and late after heart transplantation. Elevation of cTnT
      after transplantation does not seem to be directly related to ischemic time.

PMID- 9588585
TI  - Higher incidence of malignant neoplasms after heart transplantation for treatment
      of chronic Chagas' heart disease.
AB  - BACKGROUND: Heart transplantation is a new therapeutic procedure to treat heart
      failure resulting from Chagas' disease. Experimental studies have demonstrated
      neoplastic effects of benznidazole, which is used for treatment of Trypanosoma
      cruzi infection. We compared the incidence and characteristics of neoplasia after
      heart transplantation for treatment of chronic Chagas' disease with those of
      other diseases. METHODS: Sixteen patients with Chagas' disease and 75 patients
      with other diseases underwent heart transplantation. Benznidazole was
      administered to 14 patients with Chagas's disease either for prophylaxis (4
      patients) or for treatment of Chagas' disease reactivation (10 patients).
      RESULTS: The survival rate of patients in the nonchagasic group was 90% at 1 year
      and 82.4% at 2 years, and the survival rate in the chagasic group was 63% at 1
      year and 57% at 2 years. Six of 16 patients (37.5%) with Chagas' disease had
      malignant tumors after a mean follow-up time of 25.3+/-2.1 months in contrast to
      2 of 75 patients (2.7%) in the nonchagasic group after 34.6+/-3.6 months of
      follow-up. In the chagasic group, lymphoproliferative disorder was diagnosed in
      three patients, Kaposi's sarcoma in two, and squamous cell carcinoma in one
      patient. Reactivation of T. cruzi infection was diagnosed in all patients who had
      lymphoproliferative disorder. One patient without Chagas' disease had
      lymphoproliferative disorder in the lung, and another had malignant schwannoma
      affecting the skin. CONCLUSIONS: We found a higher incidence of malignant
      neoplasia after heart transplantation for treatment of chronic Chagas' disease.
      It is likely that the neoplasia is the result of chronic infection with an
      immunomodulator protozoan, immunosuppression, reactivation of the T. cruzi
      infection, or the toxicity of therapeutic intervention with benznidazole.

PMID- 9588586
TI  - Pulmonary cell death in warm ischemic rabbit lung is related to the alveolar
      oxygen reserve.
AB  - BACKGROUND: If lungs could be retrieved for transplantation from non-heart
      beating cadavers, the shortage of donors might be significantly alleviated.
      METHODS: We studied the effect of different postmortem lung conditions on
      pulmonary cell death. Lungs from 208 New Zealand white rabbits were flushed with
      trypan blue vital dye solution at intervals after circulatory arrest, fixed, and
      mounted for histologic examination. Pulmonary cells were judged to be viable on
      the basis of their ability to exclude trypan blue dye. In the control group,
      lungs were excised immediately after death and immersed in cold (4 degrees C)
      saline solution. In the other groups, cadavers were left at room temperature with
      lungs deflated, ventilated with room air or 100% oxygen or 100% nitrogen, or
      inflated with room air or 100% oxygen. RESULTS: There was a gradual increase in
      percentage (mean +/- SEM) of nonviable cells in the control group from 2.5%+/
      0.9% (preischemic value) to 18.1%+/-2.8% at 24 hours after death (p < 0.001). In
      cadavers with lungs deflated, 79.7%+/-2.1% of cells were nonviable at 24 hours
      after circulatory arrest (p < 0.001 versus control group). In contrast, room air
      ventilated cadavers showed only 21.4%+/-2.7% nonviable cells at this interval (p
      < 0.001 versus deflated group; not significant versus control group). Values in
      oxygen-ventilated animals were similar. Nitrogen-ventilated cadavers, however,
      had significantly more nonviable lung cells (73.8%+/-3.2%; p < 0.001 vs room air
      and oxygen-ventilated group, not significant vs deflated group). Oxygen-inflated
      lungs showed a parallel decrease in cell viability up to 4 hours after death when
      compared with room air-inflated cadaveric lungs, but thereafter more cells became
      nonviable in the latter group (11.1%+/-0.7% vs 19.6%+/-3.2% at 6 hours and
      48.7%+/-7.2% vs 75.5%+/-4.6% at 24 hours, respectively; p < 0.01). CONCLUSIONS:
      Postmortem room air ventilation is as good as oxygen ventilation in delaying
      pulmonary cell death, and its effect is comparable to cold storage; nitrogen
      ventilation, however, is ineffective and not different from deflation; oxygen
      inflation will preserve ischemic cells for longer intervals as opposed to room
      air inflation. Therefore the alveolar oxygen reserve seems to be the critical
      factor to protect-the lung parenchyma from warm ischemic damage.

PMID- 9588587
TI  - Pulmonary capillaritis: a possible histologic form of acute pulmonary allograft
      rejection.
AB  - Acute rejection after lung transplantation occurs commonly and is usually
      characterized histologically by a perivascular mononuclear infiltrate. We report
      five cases of pulmonary capillaritis with a histologic appearance distinct from
      typical rejection, occurring in patients ranging in age from 18 to 45 years, with
      a variety of underlying diseases including alpha1 antitrypsin deficiency,
      pulmonary hypertension, cystic fibrosis, and rheumatoid arthritis. Four of the
      five patients had alveolar hemorrhage histologically, and two had frank
      hemoptysis. Time of onset ranged from 3 weeks to many months after
      transplantation. Three cases were fulminant, and there were two deaths. In only
      one case, with methicillin-resistant Staphylococcus aureus bronchitis, could
      infection be established. All were treated with intensification of
      immunosuppressive therapy. Plasmapheresis was carried out in two cases and
      coincided with temporary improvement, but its efficacy was questionable because
      of concurrent immunosuppressive therapy. Two had recurrent biopsy-proven acute
      rejection within 6 weeks of treatment, and one had recurrent severe pulmonary
      hemorrhage that abated with total lymphoid irradiation. Our experience suggests
      that pulmonary capillaritis in lung transplant recipients can be an acute, fatal
      illness with the potential for recurrence in the survivors. We speculate that it
      represents a form of acute vascular rejection. Early pathologic diagnosis and
      aggressive immunosuppressive therapy are recommended. Although a humoral
      component was not documented, the possible response to plasmapheresis requires
      continued evaluation.

PMID- 9588588
TI  - Improved oxygenation and increased lung donor recovery with high-dose steroid
      administration after brain death.
AB  - BACKGROUND: The number of patients waiting lung transplantation greatly exceeds
      the supply of donors. This study was conducted to determine the effect of high
      dose steroid administration on oxygenation and donor lung recovery after brain
      death. METHODS: A retrospective analysis was conducted on 118 consecutive organ
      donors from January 1 through December 31, 1995. Eighty donors received high-dose
      steroids (methylprednisolone, mean 14.5+/-0.06 mg/kg) after organ procurement
      organization management began; a second group was composed of 38 patients who
      received no steroids. PaO2/FiO2 ratios were used to evaluate oxygenation. The
      number of single and double lungs transplanted served as the endpoint. RESULTS:
      No differences were noted in hemodynamics, most clinical or demographic variables
      and initial values of PaO2/FiO2 between groups. However, nonsteroid-treated
      donors showed an overall decrease in oxygenation (mean decrease in PaO2/FiO2 
      34.2+/-14), whereas steroid-treated donors had a significant and progressive
      increase in oxygenation (mean increase in PaO2/FiO2: 16+/-14) before aortic cross
      clamping (p = 0.01). Time before cross-clamping was longer in the steroid-treated
      patients (p = 0.003). The number of procured lungs was markedly greater in
      steroid-treated than nonsteroid-treated donors (25/80 patients vs 3/38; p <
      0.01). CONCLUSIONS: High-dose methylprednisolone given during donor management
      results in improved oxygenation at organ recovery. This treatment resulted in a
      significant increase in the number of lungs transplanted and may have enabled
      donors to be treated longer.

PMID- 9588589
TI  - Return to work after lung transplantation.
AB  - The social rehabilitation of lung transplant recipients becomes increasingly
      important as the results of lung transplantation improve. Although return-to-work
      (RTW) rates have been published for recipients of other organ transplants, no
      such data are available after lung transplantation. The purpose of this study was
      to determine what factors influence RTW after lung transplantation. Of 99 lung
      transplant recipients (43 single, 56 bilateral) surveyed from Denver, Colorado,
      (n = 49) and Toronto, Ontario, Canada (n = 50), 22% (n = 22) were employed, 38%
      (n = 38) were unemployed but medically able to work, 29% (n = 29) were medically
      disabled, and 10% (n = 10) had retired. The RTW rate for those medically able to
      work was 37% (22/60), and it was identical at each center (n = 11). Only Canadian
      lung transplant recipients (36%, 4/11) secured new jobs, whereas all Colorado
      lung transplant recipients returned to their previous employment (100%, 11/11). A
      stepwise discriminant analysis revealed that (1) pretransplantation employment,
      (2) a diagnosis of emphysema, cystic fibrosis, or primary pulmonary hypertension,
      (3) a self-report of being physically able to work, (4) greater functional
      improvement as measured by post-lung transplantation percent predicted forced
      vital capacity, and (5) post-lung transplantation 6-minute walk > 550 m
      positively influenced RTW. This analysis accurately profiled 82% of the employed
      and 76% of the unemployed recipients for an overall effectiveness of 79%. The
      findings of this study are that (1) a 37% employment rate for those physically
      able was comparable to other types of organ transplant recipients, (2) employment
      was not determined by the type of lung transplantation procedure (single or
      bilateral), and (3) social factors remain employment barriers for some
      recipients, but their absence did not guarantee a better employment rate.

PMID- 9588590
TI  - Treatment of aspergillus-related ulcerative tracheobronchitis in lung transplant
      recipients.

PMID- 9588591
TI  - Intrastriatal grafts from multiple donors do not result in a proportional
      increase in survival of dopamine neurons in nonhuman primates.
AB  - We examined the potential for "double grafts," i.e., grafts from two donors in
      each recipient, to enhance the total number of ventral mesencephalic dopamine
      neurons that survive grafting in adult African green monkeys. Because dopamine
      cell survival in grafts represents a small percentage of the total number of
      neurons grafted, several human clinical trials recently have employed grafts of
      tissue from multiple donors (e.g., from two to eight embryos per host recipient)
      in attempts to increase the total number of dopamine neurons that survive in
      grafts. Presumably, this is intended to elevate dopamine levels by providing more
      dopamine neurons to the damaged brain to alleviate the symptoms of parkinsonism.
      While well-developed grafts with several thousand dopamine neurons were found in
      most recipient animals, we observed a reduced total number of tyrosine
      hydroxylase positive neurons in the grafts in spite of the presence of some
      double grafts that were larger than normal. The overall growth of the grafts was
      impressive; some grafts were so large that they spanned the full dorsoventral
      extent of the caudate nucleus, probably reflecting the fact that twice as much
      tissue was implanted in each drop site in comparison to our standard protocol.
      However, some animals revealed atypical patterns of neurite outgrowth that
      appeared limited to the grafted tissue, and at least one monkey revealed
      "amorphous" grafts generally lacking in cellular structure, which suggests a
      possible rejection phenomenon. These findings raise questions about the use of
      multiple donors and suggest that the likelihood of rejection and/or cell death
      may be enhanced, which is of potential importance in the design of grafting
      strategies for clinical applications.

PMID- 9588592
TI  - Morphological and functional evidence for enhanced growth and potassium-evoked
      dopamine release in striatal grafts innervated with a patchy growth pattern. An
      in oculo nigrostriatal cograft study.
AB  - During development of the nigrostriatal dopamine system, a patchy and a diffuse
      type of striatal innervation pattern can be seen. It has been suggested that when
      fetal dopaminergic neurons, obtained from the ventral mesencephalon (VM), are
      grafted adjacent to mature striatal tissue, only the diffuse growth is induced.
      Intraocular grafting studies have indicated that the dopaminergic growth pattern
      might be influenced by the age of the target area, the lateral ganglionic
      eminence (LGE). In this study VM grafts were allowed to innervate LGE grafts of
      different ages. Fetal VM was implanted next to 2-wk-old or 26-day-old striatal in
      oculo grafts, and the resulting dopaminergic innervation of the striatal grafts
      was studied using tyrosine hydroxylase (TH) immunohistochemistry. In striatal
      grafts receiving innervation at the age of 2 wk in oculo, a patchy TH
      immunoreactive growth pattern was found, while in striatal grafts innervated at
      the age of 26 days mainly the diffuse growth pattern was seen. This implies that
      grafted striatum reached maturity at approximately 1 mo of age. The age of the
      dopaminergic neurons at dissection and grafting was also studied concerning the
      ability to induce patchy growth into mature striatum. Thus, VM dissected from 13-
      and 18-mm fetuses was implanted to either 4-mo-old LGE (grafted in sequence) or
      to LGE from the same fetus (grafted simultaneously) as controls. TH-positive
      innervation of striatal tissue, evaluated 4 wk after implantation of VM, revealed
      a patchy growth pattern in LGE grafted simultaneously with 13- and 18-mm VM.
      However, when the striatum was mature at the time of innervation, diffuse growth
      was observed in striatum innervated by VM dissected from 13-mm fetuses.
      Interestingly, patchy growth was noted in striatal areas close to VM grafts when
      the dopaminergic neurons were derived from older fetuses (CRL 18 mm).
      Furthermore, potassium-induced dopamine release was greater in striatal grafts
      exhibiting the patchy growth than those showing the diffuse pattern of
      innervation. In conclusion, patchy dopaminergic growth can be induced in mature
      striatal tissue by grafting VM from older fetuses. Functionally, potassium-evoked
      dopamine release is enhanced in dopaminergic patches. These results have
      implications in terms of finding ways to induce patchy growth when grafting to
      the mature striatum of patients suffering from Parkinson's disease.

PMID- 9588593
TI  - Immunological responses to injury and grafting in the central nervous system of
      nonhuman primates.
AB  - Allogeneic transplantation for the therapy of human Parkinson's disease is being
      considered as a viable approach at several clinical centers worldwide. As an
      attempt to understand the basic biology of central nervous system (CNS)
      transplantation, our laboratory has developed an experimental nonhuman primate
      model for human Parkinson's disease and carried out preliminary studies directed
      at evaluating the potential pathology at the graft site. In addition, studies
      have been conducted to examine whether such transplantation procedures lead to
      specific and/or nonspecific immunologic sensitization of the host or results in
      generalized immunosuppression. Groups of rhesus macaques (Macaca mulatta) were
      either controls operated (n = 6), autografted with adrenal medullary and
      peripheral nerve tissue (n = 3), or allografted with fetal mesencephalic tissue
      (n = 6). Immunohistological studies demonstrated the presence of mononuclear cell
      infiltrates as early as 1 wk and up to 1 yr postoperatively, although the
      frequency of the infiltrating cells declined with time. The infiltrates consisted
      of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+,
      CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics,
      or phenotype of the infiltrating cells in operative controls compared with
      recipients of auto- or allografts. Tissue sections obtained postoperatively
      showed low levels of major histocompatibility complex (MHC) Class I antigens and
      no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of
      tissue from the operative site was placed in vitro with media containing
      interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells
      that were predominantly CD4+ cells. Phenotypic studies of peripheral blood
      mononuclear cells (PBMC) from operative controls, auto- and allograft recipient
      monkeys performed at varying time periods postoperatively failed to show
      differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or
      monocytes. Studies on aliquots of the same PBMC failed to show major functional
      differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally,
      recipients of allogeneic mesencephalic grafts failed to show evidence of donor
      specific humoral or cellular sensitization. These data indicate that
      transplantation of autograft adrenal or allograft fetal mesencephalic tissues in
      the CNS of nonhuman primate did not induce detectable donor-specific
      sensitization nor nonspecific immunosuppression.

PMID- 9588594
TI  - Developmental expression of calcium-binding protein-containing neurons in
      neocortical transplants.
AB  - The present study examined the development of calcium binding protein-containing
      neurons in a timed series of fetal neocortical transplants. The immunoexpression
      of parvalbumin and calbindin, which are subpopulations of GABAergic neurons, have
      been widely studied in normal development and in disease and injury states.
      Because of their purported resistance to oxidative injury by their ability to
      buffer Ca++ influx, these neurons have been particularly studied following
      ischemia. Because it is likely that oxidative stress is associated with the
      grafting procedure, we sought to determine if these neurons displayed enhanced
      survival characteristics. Normally, parvalbumin and calbindin represent about 5
      10% of cortical neurons. Within 2-4 wk after grafting the expression of both
      proteins increased markedly in that a relatively larger number of neurons (27%
      for parvalbumin) were immunopositive. This increase was transitory, however, and
      by 4 mo and beyond, confocal microscopic data showed a reduction of over 50% of
      parvalbumin (+) neurons and processes. Calbindin (+) processes showed a
      qualitative change in that they were smaller with less terminal branching.
      Electron microscopy confirmed a substantial reduction in parvalbumin synaptic
      contacts. Interestingly, in older grafts, remaining parvalbumin neurons were
      those that were strongly NSE (+) suggesting a link between normal metabolism and
      Ca++ buffering in grafted neurons. It is possible that in early grafts certain
      neuronal populations transiently upregulated calcium binding proteins as a
      defensive mechanism against Ca++ influx associated with oxidative stress. Over
      time, however, following physiological normalization within grafts, the calcium
      binding protein (+) neurons are diminished, possibly due to lack of appropriate
      afferent input to the interneuronal pool.

PMID- 9588595
TI  - Bilateral fetal striatal grafts in the 3-nitropropionic acid-induced hypoactive
      model of Huntington's disease.
AB  - We investigated the 3-nitropropionic acid (3-NP)-induced hypoactive model of
      Huntington's disease (HD) to demonstrate whether fetal tissue transplantation can
      ameliorate behavioral deficits associated with a more advanced stage of HD.
      Twelve-week-old Sprague-Dawley rats were introduced to the 3-NP dosing regimen
      (10 mg/kg, i.p., once every 4 days for 28 consecutive days), and were then tested
      for general spontaneous locomotor activity in the Digiscan locomotor apparatus.
      All rats displayed significant hypoactivity compared to their pre-3-NP injection
      locomotor activity. Randomly selected rats then received bilateral intrastriatal
      solid grafts of fetal striatal (lateral ganglionic eminence, LGE) tissues from
      embryonic day 14 rat fetuses. Approximately 1/3 of each LGE in hibernation medium
      was infused into each lesioned host striatum. In control rats, medium alone was
      infused intrastriatally. A 3-mo posttransplant maturation period was allowed
      prior to locomotor activity testing. Animals receiving fetal LGE grafts exhibited
      a significant increase in locomotor activity compared to their post-3-NP
      injection activity or to the controls' posttransplant activity. Surviving
      striatal grafts were noted in functionally recovered animals. This observation
      supports the use of fetal striatal transplants to correct the akinetic stage of
      HD. To the best of our knowledge, this is the first study that has investigated
      the effects of fetal striatal transplantation in a hypoactive model of HD.

PMID- 9588596
TI  - Neuronal progenitor cells of the neonatal subventricular zone differentiate and
      disperse following transplantation into the adult rat striatum.
AB  - We have investigated the suitability of a recently identified and characterized
      population of neuronal progenitor cells for their potential use in the
      replacement of degenerating or damaged neurons in the mammalian brain. The unique
      population of neuronal progenitor cells is situated in a well-delineated region
      of the anterior part of the neonatal subventricular zone (referred to as SVZa).
      This region can be separated from the remaining proliferative, gliogenic,
      subventricular zone encircling the lateral ventricles of the forebrain. Because
      the neurons arising from the highly enriched neurogenic progenitor cell
      population of the SVZa ordinarily migrate considerable distances and ultimately
      express the neurotransmitters GABA and dopamine, we have examined whether they
      could serve as an alternative source of tissue for neural transplantation. SVZa
      cells from postnatal day 0-2 rats, prelabeled by intraperitoneal injections of
      the cell proliferation marker BrdU, were implanted into the striatum of adult
      rats approximately 1 mo after unilateral denervation by 6-OHDA. To examine the
      spatio-temporal distribution and phenotype of the transplanted SVZa cells, the
      experimental recipients were perfused at short (less than 1 wk), intermediate (2
      3 wk) and long (5 mo) postimplantation times. The host brains were sectioned and
      stained with an antibody to BrdU and one of several cell-type specific markers to
      determine the phenotypic characteristics of the transplanted SVZa cells. To
      identify neurons we used the neuron-specific antibody TuJ1, or antimembrane
      associated protein 2 (MAP-2), and anti-GFAP was used to identify astrocytic glia.
      At all studied intervals the majority of the surviving SVZa cells exhibited a
      neuronal phenotype. Moreover, morphologically they could be distinguished from
      the cells of the host striatum because they resembled the intrinsic granule cells
      of the olfactory bulb, their usual fate. At longer times, a greater number of the
      transplanted SVZa cells had migrated from their site of implantation, often
      towards an outlying blood vessel, and the density of cells within the core of the
      transplant was reduced. Furthermore, there were rarely signs of transplant
      rejection or a glial scar surrounding the transplant. In the core of the
      transplant there were low numbers of GFAP-positive cells, indicating that the
      transplanted SVZa cells, predominantly TuJ1-positive/MAP2-positive, express a
      neuronal phenotype. Collectively, the propensity of the SVZa cells to express a
      neuronal phenotype and to survive and integrate in the striatal environment
      suggest that they may be useful in the reconstruction of the brain following CNS
      injury or disease.

PMID- 9588597
TI  - Trophic effect of porcine Sertoli cells on rat and human ventral mesencephalic
      cells and hNT neurons in vitro.
AB  - The poor survival of embryonic dopaminergic (DA) neurons transplanted into
      patients with Parkinson's disease (PD) has encouraged researchers to search for
      new methods to affect the short- as well as long-term survival of these neurons
      after transplantation. In several previous rodent studies Sertoli cells increased
      survival of islet cells and chromaffin cells when cotransplanted in vivo. The
      aims of this study were to investigate whether porcine Sertoli cells had a
      positive effect on the survival and maturation of rat and human DA neurons, and
      whether the Sertoli cells had an effect on differentiation of neurons derived
      from a human teratocarcinoma cell line (hNT neurons). A significant increase of
      tyrosine hydroxylase (TH)-positive neurons of both rat and human ventral
      mesencephalic tissue was found when cocultured with Sertoli cells. Furthermore,
      there was a significantly increased soma size and neurite outgrowth of neurons in
      the coculture treated group. The Sertoli cell and hNT coculture also revealed an
      increased number of TH-positive cells. These results demonstrate that the wide
      variety of proteins and factors secreted by porcine Sertoli cells benefit the
      survival and maturation of embryonic DA neurons and suggest that
      cotransplantation of Sertoli cells and embryonic DA neurons may be useful for a
      cell transplantation therapy in PD.

PMID- 9588598
TI  - Therapeutic potential of a polymer-encapsulated L-DOPA and dopamine-producing
      cell line in rodent and primate models of Parkinson's disease.
AB  - Encapsulation of cells within polymer membranes prior to transplantation provides
      a novel means of achieving continuous, site-specific delivery of therapeutic
      molecules to the CNS. The use of encapsulated dopamine-secreting cells that can
      be transplanted directly into the striatum has particular appeal for the
      treatment of Parkinson's disease. This article provides a brief and timely review
      of the progress that has been made over the past decade using encapsulated PC12
      cells as a means of delivering dopamine and L-DOPA to the striatum in rodent and
      primate models of Parkinson's disease. The polymer membranes are well tolerated
      and biocompatible. Encapsulated PC12 cells survive in vivo for up to 6 mo, they
      release dopamine into the surrounding host striatum, and they clearly improve
      behavioral function in both dopamine-depleted rodents and primates. Although
      these results are promising, fundamental issues remain concerning the extent of
      dopamine diffusion from the polymer membranes and the number of devices needed
      for behavioral improvement, and the duration and consistency of cell viability
      and device output. Nevertheless, this technology appears to be a promising means
      of avoiding many of the practical, societal, and ethical issues that have been
      associated with other transplantation approaches.

PMID- 9588599
TI  - Liposome-mediated gene transfer into established CNS cell lines, primary glial
      cells, and in vivo.
AB  - Sufficient gene transfer into CNS-derived cells is the most crucial step to
      develop strategies for gene therapy. In this study liposome-mediated gene
      transfer using a beta-galactosidase (beta-GAL) reporter gene was performed in
      vitro (C6 glioma cells, NT2 neuronal precursor cells, 3T3 fibroblasts, primary
      glial cells) and in vivo. Using Trypan blue exclusion staining, optimal lipid
      concentration was observed in the range of 10-12 microg/mL. Under optimal
      conditions (80,000 cells/16 mm well, incubation overnight, lipid/DNA ratio =
      1:18) a high transfection rate was achieved (<9% for C6 cells; <1% for NT2
      cells). In primary cultures of glial cells a fair amount of positive stained
      cells (glial cell) was found, but the transfection efficiency was lower (<0.1%).
      A "boost-lipofection" markedly increased (twice) lipofection efficiency in C6
      cells. Expression of beta-GAL reached a maximum after 3-5 days. When the liposome
      DNA complexes were injected/infused directly into the brains of adult rats,
      several weakly stained cells could be observed in the brain region adjacent to
      the injection site. It is concluded that liposome-mediated gene transfer is an
      efficient method for gene transfer into CNS cells in vitro, but the transfection
      efficiency into the rat brain in vivo is far too low and therefore not
      applicable.

PMID- 9588600
TI  - Grafts of genetically modified Schwann cells to the spinal cord: survival, axon
      growth, and myelination.
AB  - Schwann cells naturally support axonal regeneration after injury in the
      peripheral nervous system, and have also shown a significant, albeit limited,
      ability to support axonal growth and remyelination after grafting to the central
      nervous system (CNS). It is possible that Schwann cell-induced axonal growth in
      the CNS could be substantially increased by genetic manipulation to secrete
      augmented amounts of neurotrophic factors. To test this hypothesis, cultured
      primary adult rat Schwann cells were genetically modified using retroviral
      vectors to produce and secrete high levels of human nerve growth factor (NGF).
      These cells were then grafted to the midthoracic spinal cords of adult rats.
      Findings were compared to animals that received grafts of nontransduced Schwann
      cells. Spinal cord lesions were not placed prior to grafting because the primary
      aim of this study was to examine features of grafted Schwann cell survival,
      growth, and effects on host axons. In vitro prior to grafting, Schwann cells
      secreted 1.5+/-0.1 ng human NGF/ml/10(6) cells/day. Schwann cell transplants
      readily survived for 2 wk to 1 yr after in vivo placement. Some NGF-transduced
      grafts slowly increased in size over time compared to nontransduced grafts; the
      latter remained stable in size. NGF-transduced transplants were densely
      penetrated by primary sensory nociceptive axons originating from the dorsolateral
      fasciculus of the spinal cord, whereas control grafts showed significantly fewer
      penetrating sensory axons. Over time, Schwann cell grafts also became penetrated
      by TH- and DBH-labeled axons of putative coerulospinal origin, unlike control
      cell grafts. Ultrastructurally, axons in both graft types were extensively
      myelinated by Schwann cells. Grafted animals showed no changes in gross locomotor
      function. In vivo expression of the human NGF transgene was demonstrated for
      periods of at least 6 m. These findings demonstrate that primary adult Schwann
      cells 1) can be transduced to secrete augmented levels of neurotrophic factors,
      2) survive grafting to the CNS for prolonged time periods, 3) elicit robust
      growth of host neurotrophin-responsive axons, 4) myelinate CNS axons, and 5)
      express the transgene for prolonged time periods in vivo. Some grafts slowly
      enlarge over time, a feature that may be attributable to the propensity of
      Schwann cells to immortalize after multiple passages. Transduced Schwann cells
      merit further study as tools for promoting CNS regeneration.

PMID- 9588601
TI  - Kidney cografts enhance fiber outgrowth from ventral mesencephalic grafts to the
      6-OHDA-lesioned striatum, and improve behavioral recovery.
AB  - Recent studies have demonstrated the presence of many different neurotrophic
      factors in the developing and adult kidney. Due to its production of this mixture
      of neurotrophic factors, we wanted to investigate whether fetal kidney tissue
      could be beneficial for neuritic fiber growth and/or cell survival in
      intracranial transplants of fetal ventral mesencephalic tissue (VM). A retrograde
      lesion of nigral dopaminergic neurons was performed in adult Fischer 344 male
      rats by injecting 6-hydroxydopamine into the medial forebrain. The animals were
      monitored for spontaneous locomotor activity in addition to apomorphine-induced
      rotations once a week. Four weeks following the lesion, animals were anesthetized
      and embryonic day 14 VM tissue from rat fetuses was implanted stereotaxically
      into the dorsal striatum. One group of animals received a cograft of kidney
      tissue from the same embryos in the same needle track. The animals were then
      monitored behaviorally for an additional 4 months. There was a significant
      improvement in both spontaneous locomotor activity (distance traveled) and
      apomorphine-induced rotations with both single VM grafts and VM-kidney cografts,
      with the VM-kidney double grafts enhancing the motor behaviors to a significantly
      greater degree. Tyrosine hydroxylase (TH) immunohistochemistry and image analysis
      revealed a significantly denser innervation of the host striatum from the VM
      kidney cografts than from the single VM grafts. TH-positive neurons were also
      significantly larger in the cografts compared to the single VM grafts. In
      addition to the dense TH-immunoreactive innervation, the kidney portion of
      cografts contained a rich cholinergic innervation, as evidenced from antibodies
      against choline acetyltransferase (ChAT). The striatal cholinergic cell bodies
      surrounding the VM-kidney cografts were enlarged and had a slightly higher
      staining density for ChAT. Taken together, these data support the hypothesis that
      neurotrophic factors secreted from fetal kidney grafts stimulated both TH
      positive neurons in the VM cografts and cholinergic neurons in the host striatum.
      Thus, these factors may be combined for treatment of degenerative diseases
      involving both dopaminergic and cholinergic neurons.

PMID- 9588603
TI  - Delayed VO2 kinetics during ramp exercise: a criterion for cardiopulmonary
      exercise capacity in chronic heart failure.
AB  - PURPOSE: Kinetics of VO2 at onset of constant work rate exercise was previously
      shown to be slowed in patients with chronic heart failure (CHF) compared with
      that in healthy normals. Because bicycle ergometry with ramp protocol is usually
      used for exercise testing with CHF patients, it would be of practical importance
      if it can be shown that a delay in the time interval of linear increase of VO2
      (TILIV) to work rate occurs after beginning ramp exercise. Data of central
      hemodynamics (CHF) and noninvasive cardiopulmonary parameters (CHF, normals)
      should also correlate with VO2 delay time if this parameter is related to
      cardiopulmonary exercise capacity. METHODS: Fifteen males with CHF (mean +/- SEM:
      age 52 +/- 2 yr; ejection fraction 32 +/- 4%; peak cardiac index 3.9 +/- 0.3 L x
      m(-2) x min(-1)) and 28 healthy males (50 +/- 1 yr) were assessed. During ramp
      bicycle ergometry (3 min unloaded, work rate increments of 12.5 W x min(-1)), VO2
      was measured breath by breath. RESULTS: After the onset of ramp exercise, there
      was a difference in the TILIV between patients and normals (83.7 +/- 3.6 vs 66.8
      +/- 2.9 s; P < 0.001). Significant differences between both groups were also
      found for VO2 at ventilatory threshold (VT) (10.1 +/- 0.1 vs 15.2 +/- 0.7 mL x
      kg(-1) x min(-1); P < 0.0001), VO2 at VT relative to predicted VT (58 +/- 4 vs 97
      +/- 4%; P < 0.0001), peak VO2 (13.2 +/- 1.0 vs 34 +/- 1.4 mL x kg(-1) x min(-1),
      P < 0.001), and increase of systolic blood pressure (36 +/- 7 vs 71 +/- 5 mm Hg;
      P < 0.0001). In CHF, the TILIV correlated significantly with peak cardiac index
      and VO2 at VT (r = -0.71; P < 0.005 each), relative value of VO2/kg at VT (r = 
      0.61; P < 0.03), peak VO2/kg (r = -0.63; P < 0.01), and increase of systolic
      blood pressure (r = -0.52; P < 0.02). In the normals only VO2/kg at VT correlated
      significantly with TILIV (r = -0.41; P < 0.03). In patients, stepwise regression
      analysis identified three predictors which could explain 79% of the variance of
      TILIV: VO2/kg at VT (r2 = 0.51), peak cardiac index (r2 = 0.20), and peak VO2/kg
      (r2 = 0.08). CONCLUSION: TILIV, determined at the onset of ramp exercise, is
      prolonged in CHF patients compared with that in normals and reflects severity of
      functional impairment because of reduced cardiac index and aerobic capacity.
      TILIV can provide information about changes in cardiopulmonary exercise capacity
      and thus can be used for follow-up and treatment studies in CHF.

PMID- 9588602
TI  - Cellular delivery of CNTF but not NT-4/5 prevents degeneration of striatal
      neurons in a rodent model of Huntington's disease.
AB  - The delivery of neurotrophic factors to the central nervous system (CNS) has
      gained considerable attention as a potential treatment strategy for
      neurodegenerative disorders such as Huntington's disease (HD). In the present
      study, we directly compared the ability of two neurotrophic factors, ciliary
      neurotrophic factor (CNTF), and neurotrophin-4/5 (NT-4/5), to prevent the
      degeneration of striatal neurons following intrastriatal injections of quinolinic
      acid (QA). Expression vectors containing either the human CNTF or NT-4/5 gene
      were transfected into a baby hamster kidney fibroblast cell line (BHK). Using a
      polymeric device, encapsulated BHK-control cells and those secreting either CNTF
      (BHK-CNTF) or NT-4/5 (BHK-NT-4/5) were transplanted unilaterally into the rat
      lateral ventricle. Seven days later, the same animals received unilateral
      injections of QA (225 nmol) into the ipsilateral striatum. Nissl-stained sections
      demonstrated that the BHK-CNTF cells significantly reduced the volume of striatal
      damage produced by QA. Quantitative analysis of striatal neurons further
      demonstrated that both choline acetyltransferase (ChAT)- and glutamic acid
      decarboxylase (GAD)-immunoreactive neurons were protected by CNTF implants. In
      contrast, the volume of striatal damage and loss of striatal ChAT and GAD
      positive neurons in animals receiving BHK-NT-4/5 implants did not differ from
      control-implanted animals. These results help better define the scope of neuronal
      protection that can be afforded following cellular delivery of various
      neurotrophic factors. Moreover, these data further support the concept that
      implants of polymer-encapsulated CNTF-releasing cells can be used to protect
      striatal neurons from excitotoxic damage, and that this strategy may ultimately
      prove relevant for the treatment of HD.

PMID- 9588604
TI  - Blood lactate concentrations during incremental exercise in subjects with sickle
      cell trait.
AB  - The aim of the present study was to assess blood lactate concentrations ([LA],
      mmol x L(-1)) and oxygen uptake (VO2, L x min(-1), mL x kg(-1) x min(-1)) during
      incremental exercise in subjects with sickle cell trait (SCT) only, i.e.,
      sedentary subjects with SCT without anemia and/or associated alpha thalassemia.
      Anemia was ruled out using hemoglobin (Hb) level, and alphathalassemia was ruled
      out using hemoglobin S (HbS) percentage and concomitant Hb level and mean
      corpuscular volume (MCV). Comparison was made with control subjects with normal
      Hb, matched for physical fitness, anthropometric data, and hematological
      parameters. All subjects underwent an incremental exercise test (IET) using an
      electromagnetic cycle ergometer. Ventilatory data, i.e., minute ventilation (VE,
      L x min(-1)), oxygen uptake (VO2, mL x min(-1), mL x Kg(-1) x min(-1)) carbon
      dioxide production (VO2, mL x min(-1)), ventilatory equivalent for O2(VE x VO2(
      1))and for CO2 (VE x VO2(-1)), and respiratory exchange ratio (RER, VO2 x VO2(
      1)), were collected every minute during IET and the recovery period using a
      breath-by-breath automated system. Heart rate (HR, beats x min(-1)) was measured
      every minute using an EKG. Blood sampling was done every minute during IET and
      the first 5 min of the recovery period, and then every 5 min until the 20th
      minute of recovery. [LA] were determined by an enzymatic method with a
      spectrophotometer. Comparisons of all mean cardioventilatory variables showed no
      significant differences in subjects with SCT versus controls during IET and
      recovery. In contrast, analysis of variance revealed significantly lower time
      courses of [LA] during IET (P < 0.05) and recovery (P < 0.05), whereas time
      courses of VO2 were similar (P > 0.05). We conclude that the lower [LA] exhibited
      by subjects with SCT during incremental exercise and the subsequent recovery was
      not associated with concomitant oxygen uptake impairment.

PMID- 9588605
TI  - Effects of a functional knee brace for ACL insufficiency during treadmill
      running.
AB  - PURPOSE: To assess the effects of a functional knee brace (FKB) for anterior
      cruciate ligament insufficiency (ACLI) on physiological and perceptual parameters
      during treadmill running. METHODS: Thirteen ACLI subjects (time since injury, 5.8
      +/- 5.3 yr), performed an incremental test to exhaustion and two constant load 20
      min tests, one at an intensity below lactate threshold (bLT), and the other at an
      intensity above LT (aLT) each with and without their FKB. RESULTS: Bracing had no
      effect on peak variables except for higher ratings of perceived exertion at the
      legs (RPE-L) at the velocities associated with a blood lactate concentration
      [HLa] of 4.0 mM and at peak. Bracing had no effect when exercising at bLT but did
      significantly alter the metabolic profile developed during the performance of the
      aLT tests (83 +/- 0.03% VO2peak). In particular, FKB resulted in elevated blood
      [HLa] (23%), VO2 (4%), VE (12%), VCO2 [corrected] (7%), and VE/VO2 (7%). HR and
      slow component VO2 did not differ between the brace and no brace aLT tests. RPE-L
      and RPE-knee were significantly elevated during aLT when the brace was worn.
      Suspected mechanisms include alterations in muscle recruitment patterns and/or
      occlusion. CONCLUSIONS: When ACLI individuals wear a FKB during high intensity
      straight-ahead running exercise of long duration, physiological parameters are
      affected.

PMID- 9588606
TI  - Randomized controlled trial of Protonics on patellar pain, position, and
      function.
AB  - PURPOSE: Patellofemoral pain (PFP) and abnormal patellofemoral congruence (PFC)
      are common athletic problems whose treatment remains controversial. This study
      examined the effects of a high volume of submaximal knee muscle exercise on
      objective measures of PFP and PFC under a test-retest design. METHODS: A sample
      of 100 subjects was randomly divided into two groups: control and treatment. All
      subjects of both groups were tested for PFC, using a Merchant x-ray view,
      function, via Kujala patellofemoral score (KPS), and pain, through a visual
      analog scale (VAS), initially and then 4 wk later. The treatment group exercised
      during activities of daily living (ADL) by wearing a Protonics device; the
      control group did not receive treatment. RESULTS: One-way analysis of variance
      tests found no difference between pre- and posttest results for the control group
      but found significant changes in PFC, KPS, and VAS (all P < 0.001). PFC and joint
      function improved, and PFP decreased in all subjects of the treatment group.
      CONCLUSIONS/CLINICAL RELEVANCE: It was concluded that the treatment reduced PFP
      and PFC as compared with the control. A high volume of submaximal knee exercise
      seems useful for clinical patients with PFP and abnormal PFC.

PMID- 9588607
TI  - Influence of mode and carbohydrate on the cytokine response to heavy exertion.
AB  - OBJECTIVE AND METHODS: This randomized, double-blind, placebo-controlled study
      was designed to determine the influence of exercise mode and 6% carbohydrate (C)
      versus placebo (P) beverage ingestion, on blood cell counts, plasma glucose,
      hormone, and inflammatory cytokine responses (five total samples over 9 h) to 2.5
      h of high-intensity running and cycling (approximately 75% VO2max) by 10
      triathletes who acted as their own controls. Statistical significance was set at
      P < or = 0.05. RESULTS: C relative to P ingestion (but not exercise mode) was
      associated with higher plasma levels of glucose and insulin, lower plasma
      cortisol and growth hormone, and diminished perturbation in blood immune cell
      counts. The pattern of change over time for interleukin (IL)-6 was significantly
      different between C and P conditions (P = 0.021) and between running and cycling
      modes (P < 0.001), with the lowest postexercise values seen in the C-cycling
      sessions (10.7 +/- 1.8 pg x mL(-1)) and the highest in the P-running sessions
      (51.6 +/- 14.2 pg x mL(-1)). The pattern of change over time between C and P
      conditions (but not modes) was significantly different for IL-1 receptor
      antagonist (P = 0.003), with values once again lowest for the C-cycling sessions
      (1.5 h postexercise, 301 +/- 114 pg x mL(-1)) and highest for the P-running
      sessions (1171 +/- 439 pg x mL(-1)). CONCLUSION: These data indicate that
      carbohydrate versus placebo ingestion (4 mL x kg(-1) carbohydrate or placebo
      every 15 min of the 2.5-h exercise bout) is associated with higher plasma glucose
      levels, an attenuated cortisol response, and a diminished pro- and anti
      inflammatory cytokine response.

PMID- 9588608
TI  - Immune response to exercise training and/or energy restriction in obese women.
AB  - PURPOSE: The effect of exercise training (five 45-min walking sessions/wk at 60
      75% maximum heart rate) and/or moderate energy restriction (4.19-5.44 MJ or 1,200
      1,300 kcal x d(-1)) on innate and adaptive immunity (including mitogen-stimulated
      lymphocyte proliferation (MSLP), natural killer cell activity (NKCA), and
      monocyte and granulocyte phagocytosis and oxidative burst (MGPOB) was studied in
      obese women (N = 91, age 45.6 +/- 1.1 yr, body mass index 33.1 +/- 0.6 kg x m(
      2)) randomized to one of four groups: control (C), exercise (E), diet (D),
      exercise, and diet (ED). METHODS: Aerobic power, body composition, and immune
      function were measured in all subjects before and after a 12-wk diet intervention
      period, with data analyzed using a 4 x 2 repeated measures design. All subjects
      self-reported symptoms of sickness in health logs using a precoded checklist.
      Statistical significance was set at P < or = 0.05. RESULTS: Data from this study
      indicate that although exercise training was unrelated to any significant changes
      in resting immune function, the number of days with symptoms of upper respiratory
      tract infection (URTI) was reduced relative to subjects in the nonexercise groups
      (5.6 +/- 0.9 and 9.4 +/- 1.1 sickness days, respectively, P < 0.05). Energy
      restriction and weight loss (7.9 +/- 0.7 kg) was associated with a significant
      decrease in MSLP, but no change in NKCA, MGPOB, or URTI. CONCLUSION: The data are
      consistent the viewpoint that weight loss, even at a moderate rate, is associated
      with a decrease in mitogen-stimulated lymphocyte proliferation without a change
      in various measures of innate immunity of the blood compartment.

PMID- 9588609
TI  - Three mitochondrial DNA restriction polymorphisms in elite endurance athletes and
      sedentary controls.
AB  - This study examined the associations between elite endurance athlete (EEA) status
      and three mitochondrial DNA (mtDNA) restriction fragment length polymorphisms
      (RFLPs) in the subunit 5 of the NADH dehydrogenase (MTND5) locus and one in the D
      loop region. A group of 125 Caucasian male EEA well endowed with the phenotypic
      expression of VO2max (78.9 +/- 3.8 mL x kg(-1) x min(-1), mean +/- SD) and 65
      sedentary controls (SCON: VO2max = 39.8 +/- 8.2 mL x kg(-1) x min(-1))
      participated in the study. VO2max was determined during an incremental exercise
      test on a cycle ergometer or a motor-driven treadmill. mtDNA was extracted from
      white blood cells or lymphoblastoid cell lines and specific regions were
      amplified by the polymerase chain reaction. The Pearson Chi-square statistic test
      and Fisher exact test revealed no significant association (P > 0.05) between any
      of the three mtDNA RFLPs and EEA status. The MTND5-BamHI RFLP at bp 13,470 (morph
      3) was found in 12.8% of the EEA and 12.3% of the SCON (chi2 = 0.009, P = 0.92).
      The prevalence of the MTND5-Ncil RFLP at bp 13,364 (morph 2) was 12.9% and 14%
      for the EEA and SCON, respectively (chi2 = 0.043, P = 0.83). The D-loop-KpnI RFLP
      at bp 16,133 (morph 1) was found in 5.8% of the EEA and in 1.6% of the SCON
      (Fisher exact test = 1.80, P = 0.18). The MTND5-HincII RFLP at bp 12,406 (morph
      1) was not present in this study sample. These results indicate no evidence for a
      difference in the frequency of two polymorphic restriction sites in the subunit 5
      of the NADH dehydrogenase gene of mtDNA and one in the D-loop region between
      elite endurance athletes and sedentary controls.

PMID- 9588610
TI  - Intensive training and cardiac autonomic control in high level athletes.
AB  - PURPOSE: We aimed to evaluate in a longitudinal study the effect of intensive
      training on cardiac autonomic control in athletes using 24-h heart rate
      variability analysis. METHODS: Time and frequency domain measures of heart rate
      variability were calculated from 24-h Holter monitoring in 15 high level
      bicyclists (mean age 21 +/- 4 yr) after 1 month of detraining and after 5 months
      of vigorous training. At the same times echocardiographic left ventricular mass
      and dimensions and maximal oxygen consumption (VO2max) were assessed. RESULTS: In
      detrained athletes, VO2max values, left ventricular mass and dimensions, and time
      and frequency domain measures of vagal modulation of heart rate were higher than
      in a group of untrained subjects of similar age while heart rate and the low-to
      high frequency ratio were lower, indicating an enhanced vagal modulation of heart
      rate in athletes as compared with that in control subjects. After 5 months of
      vigorous training, left ventricular mass and dimensions and VO2max increased in
      athletes, while heart rate decreased further. In contrast, no changes were
      detectable in time and frequency domain measures of heart rate variability over
      the entire 24-h and in both waking and sleeping hours. CONCLUSIONS: This study
      demonstrates that an increased cardiac vagal control is detectable in detrained
      athletes; however, after intensive training, despite a significant decrease in
      heart rate, time and frequency domain measures of heart rate variability
      reflecting cardiac vagal control remain unchanged. Thus, other mechanisms than
      changes in cardiac autonomic control could be involved in determining the
      profound bradycardia of athletes.

PMID- 9588611
TI  - Effects of F(I)O2 on leg VO2 during cycle ergometry in sedentary subjects.
AB  - In a recent study of completely sedentary normal young subjects, leg VO2max was
      reduced by hypoxia in proportion to mean capillary PO2 as F(I)O2 was reduced from
      0.15 to 0.12. However, the increase in VO2max from F(I)O2 = 0.15 to 0.21 was less
      than expected for the increase in mean capillary PO2. This finding has led us to
      hypothesize that in sedentary subjects breathing room air, VO2max is not limited
      by O2 supply but rather by oxidative capacity of mitochondria. The present study
      sought to obtain further evidence for or against this hypothesis in sedentary
      subjects by assessing leg VO2max (VO2leg) breathing 100% O2, as well as in
      normoxia and hypoxia. Data from 18 subjects studied at F(I)O2 = 0.12, 0.15, and
      0.21 and from six more studied at 0.12, 0.15, and 1.00 were analyzed. In all 24
      we measured VO2leg by arterial and venous blood sampling and thermodilution leg
      blood flow during maximal cycle ergometry at each F(I)O2. VO2leg was not
      increased by room air or 100% O2 breathing relative to that observed at F(I)O2 =
      0.15, but it was reduced while breathing 12% O2. The data at F(I)O2 = 0.12 and
      0.15 conformed to the predictions of O2 supply limitation of maximal VO2 as
      previously. These results confirm and extend our prior observations that in
      sedentary, as opposed to trained subjects, muscle VO2max is O2 supply limited
      only in hypoxia.

PMID- 9588612
TI  - Physical fitness influences water turnover and body water changes during
      trekking.
AB  - PURPOSE: This study was performed to assess water turnover and changes of body
      water during a trekking tour at moderate altitude. METHODS: Fifteen healthy
      normally trained adults participated in a 7-d backpack trek tour in the Swiss
      Alps (total walking distance: 120.5 km; cumulated altitude difference: 6990 m
      (uphill) and 7550 m downhill; lowest point: 1285 m; highest point: 3317 m). Total
      body water and water turnover were measured using deuterium dilution and
      elimination (oral load of 0.33 g 99.8% D2O per kg body weight, overnight
      equilibration period, pre- and postdose saliva samples immediately before and
      after sleep, analysis of D2O concentrations in saliva using Fourier-transform
      infrared spectroscopy, CV < 1%). Physical training state was assessed after the
      tour using the lactate-exercise intensity relationship obtained by performing 50
      W increments every 3 min on a cycle ergometer. RESULTS: Body water decreased from
      the evening of day 0 to the evening of day 4 (from 45.3 +/- 7.3 L to 43.4 +/- 7.6
      L, P < 0.05), and did not significantly decrease (43.5 +/- 7.9 L) until the
      evening of day 5 (maximum of trekking exercise intensity). Mean daily water
      turnover was 5.7 +/- 1.8 L x d(-1) corresponding to 78.7 +/- 17.5 mL x kg(-1) x
      d(-1). Body water changes and water turnover were significantly related to the
      exercise intensity obtained at the lactate threshold as well as at the level of 4
      mM lactate. CONCLUSIONS: This correlation may be in part explained by differing
      glycogen content of muscle tissue.

PMID- 9588613
TI  - Physical activity and health-related fitness in youth: a multivariate analysis.
AB  - PURPOSE: To evaluate the relationship between indicators of physical activity and
      health-related fitness in youth 9-18 yr. METHODS: A cross-sectional sample of 356
      boys and 284 girls 9-18 yr of age from phase I of the Quebec Family Study was
      studied. The sample was divided into three age groups by gender, 9-12, 13-15, and
      16-18 yr of age. Physical activity variables included two estimates of activity,
      estimated daily energy expenditure (EE) and estimated moderate-to-vigorous
      physical activity (MVPA), and one estimate of inactivity, time spent watching
      television per day (TVTIME). Health-related fitness variables were the sum of six
      skin folds (SUM), number of sit-ups in 1 min (SITUP), physical work capacity at
      150 beats x min(-1) (PWC150), and static strength of the leg (LMS). Partial
      canonical correlation was used to quantify the relationship between standardized
      (z-transformed) activity variables and health-related fitness items, controlling
      for age. RESULTS: There is a weak to moderate association between physical
      activity and fitness in youth. The first activity canonical variate is a function
      of positive loadings for EE and MVPA, with a smaller, negative loading for
      TVTIME. The first fitness variate generally includes positive loadings for PWC150
      and SITUP, with a small negative loading for the SUM and a small positive loading
      for LMS. The first canonical correlations indicate that the variance shared by
      the fitness and activity variates ranges from 11 to 21%. CONCLUSION: There is a
      significant relationship between activity and health-related physical fitness,
      but a large part of the variability (80-90%) in fitness is not accounted for by
      physical activity as measured in this study.

PMID- 9588615
TI  - Strength training: importance of genetic factors.
AB  - PURPOSE: This study focuses on the quantification of genetic and environmental
      factors in arm strength after high-resistance strength training. METHODS: Male
      monozygotic (MZ, N = 25) and dizygotic (DZ, N = 16) twins (22.4 +/- 3.7 yr)
      participated in a 10-wk resistance training program for the elbow flexors. The
      evidence for genotype*training interaction, or association of interindividual
      differences in training effects with the genotype, was tested by a two-way ANOVA
      in the MZ twins and using a bivariate model-fitting approach on pre- and post
      training phenotypes in MZ and DZ twins. One repetition maximum (1RM), isometric
      strength, and concentric and eccentric moments in 110 degree arm flexion at
      velocities of 30 degrees x s(-1), 60 degrees x s(-1), and 12 degrees x s(-1) were
      evaluated as well as arm muscle cross-sectional area (MCSA). RESULTS: Results
      indicated significant positive training effects for all measures except for
      maximal eccentric moments. Evidence for genotype*training interaction was found
      for 1RM and isometric strength, with MZ intra-pair correlations of 0.46 and 0.30,
      respectively. Bivariate model-fitting indicated that about 20% of the variation
      in post-training 1RM, isometric strength, and concentric moment at 120 degrees x
      s(-1) was explained by training-specific genetic factors that were independent
      from genetic factors that explained variation in the pretraining phenotype (30
      77%). CONCLUSIONS: Genetic correlations between measures of pre- and post
      training strength were indicative for high pleiotropic gene action and minor
      activation of training-specific genes during training.

PMID- 9588614
TI  - Physical fitness and functional limitations in community-dwelling older adults.
AB  - BACKGROUND: Conceptual models of disability have focused on disease-specific
      factors as the primary cause of disability. Functional limitations in the
      performance of basic tasks are considered primary mediators on the causal pathway
      from disease to disability. PURPOSE: The purpose of this study was to assess the
      association between three fitness components (cardiorespiratory, morphologic, and
      strength) and functional limitations. METHODS: Analyses employed data collected
      upon 161 older adults (72.5 +/- 5.1 yr) who agreed to undergo baseline testing in
      a clinical trial. RESULTS: After controlling for age, race, sex, education,
      depressive symptoms, and body mass index, all three fitness components were
      directly associated with functional limitations (P < 0.05). This study is the
      first to characterize a broad set of individual fitness components as they relate
      to functional limitations and the first to examine directly measured
      cardiorespiratory fitness within the context of existing disability models.
      CONCLUSION: These findings suggest that low fitness is a risk factor for
      functional decline independent of disease processes.

PMID- 9588616
TI  - Is there a relationship between physical activity and dietary calcium intake? A
      survey in 10,373 young French subjects.
AB  - PURPOSE: The purpose of this study was to discuss, in the light of the results of
      a survey, the calcium ration of a sample of French youth and to determine whether
      various sports activities can be related to dietary calcium intake. METHODS:
      Physical activity was evaluated using Baecke's questionnaire. Calcium intake was
      evaluated using a food frequency oriented questionnaire. The survey was performed
      on a population of 10,373 subjects (6,966 males and 3,407 females) including
      three different groups of subjects: school children and college students,
      military personnel, and athletes registered in sports federations. The mean age
      of this population was 19 +/- 9 yr, ages ranging between 7 and 50 yr. RESULTS:
      The mean amount of declared calcium intake (DCI) for the total population was
      1242 +/- 843 mg per 24 hr (mg x d(-1)). Fifty percent of this population consumed
      less than 1000 mg x d(-1) and 13% less than 500 mg x d(-1). There was no
      significant relationship between the index of activity and declared calcium
      intake. Calcium intake decreased with age and was lower in females compared to
      males. CONCLUSIONS: The subjects trained in individual endurance sports such as
      triathlon, biking, and road running have a lower DCI than subjects trained in
      team sports such as volley ball, handball, or basketball. This survey, performed
      on a large population, does indicate that for half of them daily calcium intake
      is below the threshold of 1,000 mg x d(-1) considered the daily requirement
      covering the needs of a population without age or gender distinction and that
      calcium intake is not related to the level of physical activity.

PMID- 9588618
TI  - Impact of rapid weight loss on cognitive function in collegiate wrestlers.
AB  - PURPOSE: The purpose of this study was to examine the effects of rapid weight
      loss (RWL) on cognitive function in collegiate wrestlers. METHODS: Wrestlers (N =
      14) and controls (N = 15) were college-aged males who were tested at three
      different times: baseline, RWL, and rehydration. Wrestlers practiced RWL in
      preparation for competition while controls maintained normal body weight and
      dietary practices throughout the study. At each test session, blood glucose,
      hemoglobin (Hgb), hematocrit (Hct), plasma volume (PV), and body weight were
      measured. Subjects also completed mood and hypoglycemic profiles as well as five
      short cognitive tests. RESULTS: Two-way ANOVA and post-hoc tests revealed poorer
      performance for wrestlers than controls in two recall tests as well as greater
      mood negativity for the wrestlers after RWL. With RWL, between group differences
      were also evident in hypoglycemic profile, blood glucose, PV, and body weight.
      All measures returned to near baseline values after rehydration, suggesting that
      all physiological and cognitive effects associated with RWL were reversible. It
      is possible that precompetition anxiety may partially explain the results.
      CONCLUSIONS: RWL in collegiate wrestlers before a competition appears to cause
      physiological effects that are accompanied by transient mood reduction and
      impairment of short-term memory. The potential negative impact of this practice
      on the student-athlete should be considered.

PMID- 9588617
TI  - Acute exercise reduces caffeine-induced anxiogenesis.
AB  - PURPOSE: This experiment examined the influence of acute exercise on anxiety
      following caffeine-induced elevations in self-rated anxiety. METHODS: Eleven
      physically active, moderately fit males aged 25.1 +/- 3.8 yr completed four
      conditions in a within-subject, counterbalanced design involving 60 min of (1)
      cycling at 60% VO2peak or (2) quiet rest following placebo consumption (800 mg of
      lactose), as well as (3) cycling at 60% VO2peak and (4) quiet rest following 800
      mg of caffeine. State anxiety and blood pressure were assessed 10 min before and
      10 and 20 min after the conditions. RESULTS: A main effect for drug (caffeine vs
      placebo) determined by repeated measures ANOVA, (F(1,8) = 9.77; P = 0.01),
      indicated that state anxiety was elevated by caffeine. Drug effects were not
      obtained for blood pressure. Experimental hypotheses were tested by drug-by
      condition (exercise vs quiet rest)-by-time (10 and 20 min postcondition) repeated
      measures ANOVA of change scores from the precondition baseline. A main effect for
      drug (F(1,8) = 5.81; P = 0.043) indicated that reductions in state anxiety were
      larger after caffeine ingestion. A condition-by-time effect (F(1,8) = 5.02; P =
      0.055) indicated greater reductions in state anxiety 20 min after exercise
      compared with quiet rest. A condition effect for systolic blood pressure (F(1,10)
      = 4.56; P = 0.058) and condition-by-time interactions for diastolic (F(1,10) =
      8.87; P = 0.014) and mean arterial blood pressures (F(1,10) = 8.46; P = 0.016)
      indicated reductions after exercise but not after quiet rest following both
      caffeine and placebo. CONCLUSIONS: We conclude that exercise can reduce anxiety
      elevated by a high dose of caffeine.

PMID- 9588619
TI  - "Leg spring" characteristics and the aerobic demand of running.
AB  - PURPOSE: By applying a simple, linear mass-spring model to running, the
      normalized leg spring stiffness (Kleg), the normalized effective vertical
      stiffness (Kvert), and the mass-specific mechanical power output of the spring
      (Psp) were determined and correlated with aerobic demand. The purpose of the
      study was to determine whether leg spring characteristics explain any of the
      interindividual variability observed in aerobic demand at a given submaximal
      running speed. METHODS: Recreational runners (N = 16) ran on a treadmill at 3.35
      m x s(-1) for physiological measures and overground for biomechanical measures.
      The latter included a sagittal plane video record of the running motion and
      ground reaction data. RESULTS: We found no relationship between the aerobic
      demand of running and Kleg (r = -0.18), an inverse relationship between aerobic
      demand and Kvert (r = -0.48), and a positive correlation between aerobic demand
      and Psp (r = 0.45). CONCLUSIONS: The inverse relationship between Kvert and
      aerobic demand indicates that less economical runners possess a more compliant
      running style during ground contact. This running style may place greater force
      demands on extensor musculature.

PMID- 9588620
TI  - Effect of rolling resistance on poling forces and metabolic demands of roller
      skiing.
AB  - OBJECTIVE: To examine the effect of an increase in roller ski rolling resistance
      on the physiological and upper body demands of roller skiing with the V2
      alternate technique. METHODS: Nine highly skilled cross-country skiers roller
      skied at three paced speeds on a flat oval loop using roller skis with high (HiR)
      and low (LowR) rolling resistance. Oxygen uptake (VO2), heart rate, and poling
      forces were measured during the last 30 s and rating of perceived exertion (RPE)
      was requested immediately after each 4-min bout of roller skiing. RESULTS: VO2
      and all force-related variables increased significantly with speed and were
      higher (P < 0.01) for HiR at given speeds. Poling time was similar between HiR
      and LowR, whereas poling recovery time was shorter (P = 0.0002) and cycle rate
      was higher (P = 0.002) for HiR. For given VO2 levels, peak and average forces,
      heart rates, and RPE values were similar between HiR and LowR, whereas average
      poling force across the cycle was greater (P = 0.006) and duty cycle (i.e.,
      percentage of cycle when poling forces were applied) was higher (P = 0.0001) with
      HiR. CONCLUSIONS: 1) The decrease in poling recovery time and increase in cycle
      rate associated with an increase in roller ski rolling resistance is comparable
      to the effect previously observed from increasing grade and probably occurs as a
      means of limiting deceleration. 2) Since changes in rolling resistance do not
      alter the relationships of RPE and heart rate with VO2, the central
      cardiovascular adaptations from roller ski training should not be affected by the
      rolling resistance of the roller skis. 3) Higher resistance roller skis are
      likely to induce greater upper body aerobic adaptations than lower resistance
      roller skis.

PMID- 9588621
TI  - Effect of elevated blood FFA levels on endurance performance after a single fat
      meal ingestion.
AB  - PURPOSE: This study was designed to examine the effect of elevated blood free
      fatty acid (FFA) levels on carbohydrate (CHO) oxidation and cycling performance
      after ingesting a single fat meal (FM). METHODS: Four hours before cycling
      exercise, nine trained males consumed either a FM (4711 kJ; 30% CHO, 61% fat, and
      9% protein) or control meal (CM) (4877 kJ; 58% CHO, 31% fat, and 11% protein).
      The intensity of exercise employed was 67% of the maximal oxygen consumption
      (VO2max) for the first 120 min of exercise, followed by an increase to 78%
      VO2max. RESULTS: The FM ingestion significantly (P < 0.05 and P < 0.01) elevated
      serum FFA levels above those resulting from CM ingestion almost throughout the
      entire exercise. A significantly (P < 0.05 and P < 0.01) lower respiratory
      exchange ratio in the FM versus the CM trials was observed during the first hour
      of exercise. This was accompanied by a significantly greater amount of fat
      oxidized at 20 (P < 0.01) and 60 min (P < 0.05) of FM trials and a significantly
      smaller amount of CHO oxidized at 20 min (P < 0.05) of FM trials. However,
      endurance time and work production did not differ between the FM (141 +/- 8 min,
      134333 +/- 6049 kg x m (SEM)) and CM (138 +/- 5 min, 131450 +/- 4737 kg x m)
      trials. Also, there were no significant differences in oxygen consumption, heart
      rate, and perceived exertion or in glucose, lactate, and triglyceride levels in
      the blood. CONCLUSIONS: These results suggest that the elevated blood FFA levels
      after a single FM ingestion reduce CHO oxidation early in exercise, but this
      decrease in CHO oxidation would not be adequate enough to contribute to an
      increased endurance.

PMID- 9588622
TI  - Comparison of body composition assessment among lean black and white male
      collegiate athletes.
AB  - Variations in the density of the fat-free mass (DFFM) across ethnic groups is a
      critical factor that invalidates the use of body fat equations. It has also been
      suggested that resistance trained athletes may have higher body densities (BDs)
      than untrained subjects. Thus, the validity of using anthropometric (ANT)
      equations, which have mainly been derived on white nonathletic groups, has been
      questioned for athletic white and black men. This study compared BD and percent
      body fat (%BF) between 34 white (20 +/- 1 yr, 184 +/- 11 cm, 84 +/- 12 kg, 25 +/-
      3 BMI) and 30 black (20 +/- 1 yr, 182 +/- 9 cm, 84 +/- 12 kg, 25 +/- 2 BMI) male
      collegiate athletes and determined the accuracy of 5 ANT equations in estimating
      %BF. Subjects were underwater weighed (UWW), and skinfold measurements were
      obtained from the chest, mid-axillary, abdomen, suprailiac, subscapula, triceps,
      and thigh. BD was obtained from UWW and estimated from the five skinfold
      equations. From UWW, significant (P < or = 0.05) differences were found for BD
      (1.075 +/- 0.007 vs 1.0817 +/- 0.009), but not for %BF (10.49 +/- 2.8 vs 11.59 +/
      3.4) for white and black subjects, respectively. Differences were noted for
      subcutaneous skinfold sites (abdominal (vertical), suprailiac, and thigh), sum of
      three and seven skinfolds, and proportion of subscapular subcutaneous fat. One
      out of five and five out of five ANT equations (Siri conversions) yielded
      significantly lower estimates compared with UWW %BF for the white and black
      athletes, respectively. Use of the Schutte equation for the black athletes
      resulted in overpredictions of %BF for five out of five equations. In addition,
      the Schutte equation offered slightly greater accuracy than did the Siri equation
      for estimating %BF in black athletes. These data confirm earlier concerns that
      ANT equations derived on general populations may not be as accurate for athletic
      populations and also suggest that correction equations are necessary for
      converting BD into %BF for populations differing with respect to race or training
      status.

PMID- 9588623
TI  - Calibration of the Computer Science and Applications, Inc. accelerometer.
AB  - PURPOSE: We established accelerometer count ranges for the Computer Science and
      Applications, Inc. (CSA) activity monitor corresponding to commonly employed MET
      categories. METHODS: Data were obtained from 50 adults (25 males, 25 females)
      during treadmill exercise at three different speeds (4.8, 6.4, and 9.7 km x h(
      1)). RESULTS: Activity counts and steady-state oxygen consumption were highly
      correlated (r = 0.88), and count ranges corresponding to light, moderate, hard,
      and very hard intensity levels were < or = 1951, 1952-5724, 5725-9498, > or =
      9499 cnts x min(-1), respectively. A model to predict energy expenditure from
      activity counts and body mass was developed using data from a random sample of 35
      subjects (r2 = 0.82, SEE = 1.40 kcal x min(-1)). Cross validation with data from
      the remaining 15 subjects revealed no significant differences between actual and
      predicted energy expenditure at any treadmill speed (SEE = 0.50-1.40 kcal x min(
      1)). CONCLUSIONS: These data provide a template on which patterns of activity can
      be classified into intensity levels using the CSA accelerometer.

PMID- 9588625
TI  - Mutational and biochemical analysis of dopamine in dystonia: evidence for
      decreased dopamine D2 receptor inhibition.
AB  - The dystonias are a group of serious movement disorders characterized by
      involuntary muscle spasms of different parts of the body. We recently proposed
      that hypofunction of dopamine D2 receptor-mediated inhibition of the indirect
      output pathway of the basal ganglia can result in dystonia. In this review, we
      discuss the results of a variety of genetic and biochemical studies in light of
      this hypothesis. Several forms of early-onset dystonia show distinct autosomal
      dominant, recessive, or X-linked genetic transmission patterns. Late onset forms
      of dystonia, though not showing clear Mendelian transmission patterns, also
      appear to be highly familial. Recently, several genetic-linkage locations have
      been identified for early-onset dystonia and for two of these loci, mutations
      decreasing dopamine synthesis have been demonstrated. Biochemical studies of
      monkeys and man also demonstrate that several types of dystonia occur in a
      dopamine-deficiency state. Similarly, mice strains developed to be deficient in
      several dopamine-pathway components have motor abnormalities consistent with
      dystonia. Hypofunction of the dopamine D2 receptor-mediated inhibition of the
      indirect output pathway of the putamen may be a common feature of many of these
      heritable and secondary dystonic syndromes.

PMID- 9588624
TI  - Coupling of D1 and D5 dopamine receptors to multiple G proteins: Implications for
      understanding the diversity in receptor-G protein coupling.
AB  - Dopamine receptors are a subclass of the super family of G protein-coupled
      receptors, that transduce their effects by coupling to specific G proteins.
      Within the dopamine receptor family, the adenylyl cyclase stimulatory receptors
      include the D1 and D5 subtypes. The D1 and D5 dopamine receptors are genetically
      distinct, sharing >80% sequence homology within the highly conserved seven
      transmembrane spanning domains, but displaying only 50% overall homology at the
      amino acid level. When expressed in transfected GH4C1 rat pituitary cells, both
      D1 and D5 receptors stimulate adenylyl cyclase and have identical affinities
      toward dopaminergic agonists and antagonists. In order to analyze specific
      signaling pathways mediated by activation of either D1 or D5 receptors, we have
      identified the G proteins that are coupled to these receptors. Through functional
      analyses and competition binding studies, and from immunoprecipitation
      techniques, using antisera against the various alpha subunits of G proteins, we
      have established that both D1 and D5 receptors couple to G(s)alpha. In addition,
      D1 receptors are also coupled to G(o)alpha. Since G(o)alpha has been implicated
      in the regulation of Ca2+, K+, and Na+ channels, this finding would suggest that
      D1 receptors can mediate the functional activity of these ion channels. There is
      also evidence to indicate that D5 receptors couple to G(z)alpha, a novel G
      protein abundantly expressed in neurons. Thus, despite similar pharmacological
      properties, such differential coupling of D1 and D5 receptors to G proteins other
      than G(s)alpha, indicates that dopamine can transduce varied signaling responses
      upon the simultaneous stimulation of both these receptors.

PMID- 9588626
TI  - Making sense of the multiple MAP-2 transcripts and their role in the neuron.
AB  - Microtubule-associated protein-2 (MAP-2) is a family of heat-stable,
      phosphoproteins expressed predominantly in the cell body and dendrites of
      neurons. Three major MAP-2 isoforms, (MAP-2a, MAP-2b, MAP-2c) are differentially
      expressed during the development of the nervous system and have an important role
      in microtubule dynamics. Several MAP-2 cDNA clones that correspond to the major
      MAP-2 transcripts and additional, novel MAP-2 transcripts expressed in the CNS
      and PNS have been characterized. The transcripts result from the alternative
      splicing of a single MAP-2 gene consisting of 20 exons. Studies are now being
      directed toward understanding the role of the multiple MAP-2 forms that contain
      novel exons in the nervous system. The expression, localization, and possible
      functions of the newly identified spliced forms are the focus of this review.

PMID- 9588628
TI  - Geographic differences in bacterial meningitis: less may be as interesting as
      more.
AB  - Many reports in the last decade have described populations with a high incidence
      of bacterial meningitis, especially amongst indigenous groups in industrialised
      countries, such as North American Eskimos and Apache Indians and Australian
      Aborigines, particularly with meningitis due to Haemophilus influenzae type b
      (Hib). Lack of evidence that invasive Hib disease, including meningitis, is a
      significant health problem has been attributed to lack of appropriate data,
      either due to lack of laboratory and clinical facilities, such as in most less
      industrialised countries, or lack of study. Host differences in immune response,
      though known to be important for individual susceptibility to Hib disease and
      bacterial meningitis, have not been thought important on a population level. Good
      quality epidemiologic data now available from Hong Kong and Japan, based on sound
      laboratory methods, have shown bacterial meningitis, particularly due to Hib and
      Neisseria meningitidis, to be significantly less common than in predominantly
      Caucasian populations in various industrialised countries. Differences in host
      immune response to these capsular polysaccharides seems the most likely
      explanation for this observation. It is interesting that other immunologically
      mediated disorders such as Kawasaki disease and systemic lupus erythematosis have
      a relatively high incidence in Sino Japanese populations, lending plausibility to
      inherited differences in immune response as a mechanism for these observations.

PMID- 9588629
TI  - Neonatal cranial ultrasound screening for intraventricular haemorrhage.
AB  - The cost effectiveness of performing routine neonatal cranial ultrasound scans to
      diagnose intraventricular haemorrhage (IVH) on cohorts of high risk infants is in
      question. In the early 1980s cranial ultrasound scans were performed on preterm
      infants to expand knowledge of the incidence, aetiology, pathogenesis and
      evolution of IVH. In many neonatal units high risk infants are scanned on days 5
      7 and 10-14 and prior to discharge for extremely low birthweight (ELBW) infants.
      Cranial ultrasound scanning is often used as a surrogate for assessment of
      neurodevelopmental outcome with information from meta analyses used to counsel
      parents about the likelihood of subsequent neurosensory disability.

PMID- 9588631
TI  - Guidelines for the funding of paediatric research by formula companies. The
      Australian College of Paediatrics.

PMID- 9588630
TI  - Lead exposure and cognitive development: persistence and a dynamic pattern.
AB  - OBJECTIVES: Although enormous effort has been focused over the past two decades
      on examining the potential adverse effects of exposure to environmental lead on
      human health, there has been a debate over the persistence and dynamic pattern of
      these effects. METHODOLOGY: Articles relevant to this issue which were published
      between January 1982 and December 1996 were retrieved from Medline and adjunct
      searching methods (i.e. hand searching of key journals, review of the
      bibliographies of reports known to be relevant, consulting with experts, and use
      of Science Citation Index). RESULTS: Currently available epidemiological evidence
      suggests that 'low' level exposure to lead in early childhood is likely to cause
      a moderate but real and detectable effect on cognitive development, and this
      effect appears to persist into later childhood. The findings from four long-term
      prospective studies seem to support the constant decrement model which assumes
      that cognitive deficits resulting from early lead exposure persist over an
      extended period of time even when exposure decreases. CONCLUSION: From a public
      health perspective, it is highly desirable and prudent to reduce the dispersive
      uses of lead. Since lead is ubiquitous and persistent in the environment and may
      have a subtle and persistent effect on cognitive development, how to set the
      environmental standards for lead exposure is an important scientific issue still
      open for debate.

PMID- 9588633
TI  - The use of an interactive computer program for the education of parents of
      asthmatic children.
AB  - OBJECTIVE: To assess whether an interactive computer program improves the asthma
      knowledge of parents of asthmatic children attending a respiratory clinic, and to
      assess the acceptability of this educational method to parents. METHODOLOGY:
      Parents' knowledge was assessed before and one month after using the computer
      program. Knowledge scores were compared using paired Student's t-tests. Parents'
      comments about the program were invited. RESULTS: Whilst knowledge scores
      improved after exposure to the computer program, the improvement was not
      statistically significant (P=0.06). However, parents felt subjectively that the
      program was both enjoyable and useful to them. CONCLUSION: Used as the sole
      instrument for asthma education, the program did not produce a large increase in
      asthma knowledge in the study population. It was, however, universally popular
      and may prove useful in other settings and in combination with other forms of
      asthma education.

PMID- 9588632
TI  - Psychosocial aspects of adolescent cancer survival.
AB  - OBJECTIVE: The purpose of this research was to examine the psychosocial status of
      adolescent cancer survivors and compare them with healthy peers. It has been
      suggested in previous research that the majority of survivors display equivalent
      levels of psychosocial functioning post-treatment as compared with healthy
      controls. However, despite successful treatment, survivors may have to adjust to
      living with a chronic illness and its associated late effects interspersed across
      the lifespan (e.g. infertility, cognitive deficits, heart complications). Whilst
      young people appear to have similar levels of psychosocial functioning, avoidance
      strategies such as denial may result in previous research findings being
      confounded and in underestimating the true psychosocial status of survivors. It
      is important to understand the psychosocial status of survivors in order to
      optimise their quality of life. METHODOLOGY: Coping mechanisms, anxiety levels
      and self-concepts of 32 adolescent cancer survivors, predominantly Acute
      Lymphoblastic Leukaemia (ALL) were compared with 34 healthy adolescents (age
      range 12-17 years), via a mailout. RESULTS: Survivors' self-reports suggest no
      overt psychological dysfunctioning. Whilst the two groups shared similar coping
      strategies, survivors were found to be less anxious than peers, with a tendency
      to employ avoidance strategies to deal with problems faced in adolescence. Age,
      gender and specific illness variables, such as age at diagnosis and time since
      treatment, were strong predictors of psychological outcome. CONCLUSIONS: Results
      can be interpreted as suggesting that whilst cancer survivors have a similar
      psychosocial profile to healthy peers, they are more likely to utilise avoidance
      strategies to manage problems.

PMID- 9588634
TI  - The use of alternative therapies by children with asthma: a brief report.
AB  - OBJECTIVE: To identify the nature and prevalence of alternative therapies used by
      children with asthma attending a children's hospital. METHODOLOGY: Subjects
      consisted of a consecutive series of 51 children with asthma aged 1-6 years who
      were attending the Women's and Children's Hospital, South Australia. Parents of
      the children completed a questionnaire describing the use of alternative
      therapies by the children. RESULTS: Approximately 55% of children used
      alternative therapies for asthma management. Therapies used most commonly were
      massage, relaxation exercises, diet therapy and vitamins. There was no
      significant difference in the age, asthma severity, length of time since
      diagnosis or presence of another illness amongst children who did or did not use
      alternative therapies. CONCLUSIONS: A substantial proportion of children with
      asthma who attend paediatric clinics use alternative therapies. Paediatricians
      should be aware of this and be prepared to discuss alternative therapies with
      parents. This may facilitate more open doctor-patient relationships and better
      management of children's asthma.

PMID- 9588635
TI  - Isoflavone content of infant foods and formulas.
AB  - OBJECTIVE: The purpose of this study was to investigate the phytoestrogen content
      of different foods, formulas and drinks that may be consumed by infants during
      their first year of life in an attempt to define levels of exposure on different
      feeding regimens. METHODOLOGY: High performance liquid chromatography (HPLC) was
      used to determine the levels of genistein, daidzein, biochanin A, formononetin
      and equol in samples purchased from Australian supermarkets. Single lots of
      duplicate or triplicate samples of soy beverages, cow's milks, infant formulas
      and infant yoghurts were analysed. RESULTS: All foods tested contained
      isoflavones, at varying levels, suggesting that exposure to these compounds is
      almost ubiquitous. Casein-based infant formulas contained between 0.001 and 0.03
      mg L(-1). Soy-based infant formulas ranged from 17.2 to 21.9 mg L(-1) with the
      values detected in yoghurt at similar levels to that of cow's milk. For
      comparison, the soy-based beverages (which are not recommended for use under 12
      months of age) contained levels of isoflavones from 22.9 to 71.5 mg L(-1).
      CONCLUSIONS: Given the relatively broad choice of infant foods becoming
      available, exposure to dietary isoflavones during the first year of life is
      virtually ubiquitous. The exposure may be higher if soy infant formulas are
      consumed, however, the levels attained appear to fall within normal physiological
      boundaries.

PMID- 9588636
TI  - Farm and tractor-related fatalities in children in South Australia.
AB  - OBJECTIVE: To analyse the circumstances surrounding farm and tractor-related
      childhood fatalities in South Australia, to identify potentially dangerous
      situations and to delineate prevention strategies. METHODS: A retrospective
      search of files was conducted at the Women's and Children's Hospital Department
      of Histopathology from 1981 to 1996, and the State Coroner's Office from 1988 to
      1996. RESULTS: Fifteen fatalities were identified comprising 11 boys and four
      girls (age range, 2 years 11 months to 13 years; average, 6 years). Activities
      prior to death included riding on a tractor/trailer (n=8); playing near a field
      grain storage bin (n=2); playing near machinery (n=2); sleeping in a car near a
      burn off (n=1); walking around a dam (n=1) and riding as a passenger on a
      motorbike (n=1). Causes of death included multiple skull fractures and cerebral
      damage (n=11), asphyxia (n=2), drowning (n=1) and incineration (n=1).
      CONCLUSIONS: The most dangerous activity involved children riding unrestrained on
      tractors; falls resulted in extensive injuries from tractor rear wheels or towed
      machinery. Allowing children on farms to ride on tractors or machinery only if
      there is a safe seat with a restraining harness would substantially reduce the
      number of fatal farm-related childhood injuries in South Australia.

PMID- 9588638
TI  - Postextubation chest X-rays in neonates: a routine no longer necessary.
AB  - OBJECTIVES: To ascertain the incidence of postextubation atelectasis (PEA) in
      neonates, to delineate any objective differences between those infants with PEA
      and those without, and to see if any of those differences were predictive of the
      need for a postextubation chest X-ray (CXR). METHODS: This is a retrospective
      review of all infants ventilated in 1994. For each separate period of extubation
      the medical, physiotherapy and nursing notes were examined. Data were collected
      on birthweight, gestational age, duration of ventilation, age at extubation,
      ventilation requirements pre-extubation, pre- and postextubation arterial carbon
      dioxide tensions (PaCO2) and oxygen requirements, the number of episodes of
      bradycardia and apnoea, the pulse and respiratory rates pre- and postextubation,
      and the use of nasal continuous positive airway pressure (NCPAP). It was routine
      practice throughout 1994 for all ventilated babies to have a CXR 6 h
      postextubation. Each postextubation CXR was examined by one of the authors (MWD)
      for the presence of atelectasis and other diagnoses. PEA was defined as any
      atelectasis present on the postextubation CXR that was not present on the pre
      extubation CXR. RESULTS: The overall incidence of any PEA was 2.5% (6/236). In
      those babies with PEA, the increase in oxygen requirement at 1 and 6 h
      postextubation was higher (change in inspired oxygen (deltaFiO2) of 0.05 vs
      0.015, P=0.043 and deltaFiO2 of 0.045 vs 0.0, P=0.033, respectively). There was a
      higher incidence of the need for NCPAP some time after extubation (2/4 vs 9/163,
      P<0.001). No infant with PEA required reintubation and ventilation. CONCLUSIONS:
      In this nursery the incidence of PEA is low with no significant morbidity.
      Postextubation CXRs should be performed on only those infants who have an
      increase in oxygen requirement postextubation or become symptomatic with new or
      increasing respiratory distress, and to follow up atelectasis on the most recent
      pre-extubation CXR.

PMID- 9588637
TI  - Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered
      dose inhaler.
AB  - OBJECTIVE: To compare the efficacy of salbutamol delivered by jet nebuliser (JN)
      with salbutamol via a pressurised metered dose inhaler (PMDI) and a large volume
      spacer (Volumatic) for management of acute asthma. STUDY POPULATION: A total of
      160 children aged from 4 to 12 years presenting to an Emergency Department with
      acute asthma. METHODS: The study was of multicentre (n=5) randomised, double
      blind, parallel design. Children weighing less than 25 kg received salbutamol 2.5
      mg via the JN or 600 microg (six puffs) from the PMDI. Children over 25 kg
      received salbutamol 5 mg via the JN or 1200 microg (12 puffs) via the PMDI.
      Clinical score (range 0-12) and PEF (over 7 years) were recorded at baseline and
      15, 30, 45 and 60 mins post administration. RESULTS: The improvement from
      baseline at 30 min in the clinical score was 1.87 for JN and 1.43 for PMDI
      (P=0.09) and at 60 min was 2.15 for JN and 1.12 for PMDI (P=0.0001). The
      improvement in PEF at 30 min was 51 L min(-1) for JN and 27 L min(-1) for PMDI
      (P=0.0007) and at 60 min was 57 L min(-1) for JN and 31.5 L min(-1) for PMDI
      (P=0.001). CONCLUSION: Administration of salbutamol via a PMDI and a large volume
      spacer device provides effective relief in the management of acute asthma in
      children, but to a lesser extent than a jet nebuliser. This difference may
      represent a dose response effect.

PMID- 9588639
TI  - Efficacy and safety of oral desmopressin in the treatment of primary nocturnal
      enuresis in Asian children.
AB  - OBJECTIVE: To determine the efficacy and safety of oral desmopressin (DDAVP)
      treatment in Asian children with nocturnal enuresis. METHODOLOGY: This was a
      multicentre randomized placebo-controlled double-blind cross-over study. Patients
      were randomized to either active treatment with oral 400 mg DDAVP or placebo,
      with a 2-week medication-free period between the cross-over. Children with
      primary monosymptomatic nocturnal enuresis, aged between 7 and 18 years, with a
      minimum frequency of wetting of 6 nights or more during a 2-week observation
      period were recruited. Efficacy was measured by reduction in the average number
      of wet nights per week. RESULTS: Of the 37 children initially recruited, the
      outcomes for 34 children were included in the final cross-over analysis, as they
      had complete data for both the treatment periods. Statistical analysis by ANOVA
      showed that there was no significant difference between the medication-free
      period and the pretreatment period. However, the average number of wet nights per
      week for the DDAVP treatment period (2.5+/-2.7) was significantly lower than that
      of the placebo treatment period (4.5+/-2.1) (P < 0.0001). In terms of the safety
      profile, there was no significant change in bodyweight, blood pressure, serum
      sodium, serum osmolality, and urine osmolality following DDAVP treatment.
      CONCLUSION: Oral DDAVP is a safe and efficacious drug for the short-term
      treatment of children with primary nocturnal enuresis.

PMID- 9588640
TI  - Symptomatic urinary tract infection in preschool Australian children.
AB  - OBJECTIVE: To describe the demographic and clinical features, short-term
      outcomes, microbiology and renal tract abnormalities of a cohort of young
      Australian children with symptomatic urinary tract infection. METHODOLOGY: A
      total of 304 children < 5 years with their first documented symptomatic urinary
      tract infection who presented consecutively to the Emergency Department of a
      paediatric hospital between March 1993 and December 1994 and without a known
      predisposing cause were identified and details of their acute illness were
      recorded. Renal tract sonography, micturating cystourethrography and Tc-99 m
      dimercaptosuccinic acid scintigraphy (DMSA) were routinely performed. RESULTS: Of
      those who presented with urinary tract infection, 169 were boys and 135 girls;
      64% were less than 1 year of age. For children from the local community, the
      cumulative incidence of urinary tract infection within the first 5 years of life
      was estimated to be 1.9% for boys and 1.8% for girls. There were no significant
      differences in illness characteristics according to mode of referral or
      geographical locality. Presenting symptoms were generally nonspecific and not
      referrable to the urinary tract. There were no deaths. One per cent of children
      required ventilatory support, and bacteraemia occurred in 6%, all of whom were
      under 6 months of age. E. coli was the causal organism in 84%, and a high in
      vitro resistance to ampicillin/ amoxycillin (54%) was demonstrated by the
      pathogens isolated. Bacteriuria was eradicated in 99% with antimicrobial
      treatment. In this setting, the sensitivities of dipstick urinalysis (leucocyte
      esterase+/-nitrites) and pyuria on microscopy (>10 x 10(6) white cells L(-1))
      were 85%. Abnormal DMSA scintigraphy was detected in 39%, vesicoureteric reflux
      in 28%, and obstructive uropathy in 1%. CONCLUSIONS: This study provides current
      and local data on a large sample of children <5 years with urinary tract
      infection, which are useful to clinicians who manage children at risk of the
      condition.

PMID- 9588641
TI  - The sleep patterns of infants and young children with gastro-oesophageal reflux.
AB  - OBJECTIVE: Sleep disturbance in gastro-oesophageal reflux disease (GORD) in
      infants and young children has not been systematically studied nor has this
      manifestation been compared with population norms. METHODS: Sleep patterns of 102
      infants and children aged 1 to 36 months with and without GORD, defined by pH
      monitoring, were analysed using the same questionnaire as in recent studies of
      normal sleep behaviour in this age range. Main outcome measures included time
      taken to settle at night, the number of night time wakenings requiring parental
      intervention, day time sleep patterns and parents problems with their childs'
      sleep behaviour. RESULTS: Compared with the population norms (n=3102), those with
      GORD (n=76) had greater prevalence of night time waking >3/night (50% vs 13% aged
      3-12 months; 60% vs 10% aged 12-24 months, P<0.001), requirement of parental
      intervention (82% vs 55% aged 3-12 months, P<0.05; 92% vs 55% aged 12-24 months,
      P<0.001), significantly delayed onset of sleeping through the night, and greater
      prevalence of daytime sleep beyond 24 months. Similar but less striking
      differences were seen comparing those with (n=76) and without GORD (n=26).
      CONCLUSIONS: Sleep interruption occurs more frequently in infants and children
      with GORD than population norms. Objective evaluation of infants and children
      with sleep disturbance after the age of 3 months may avoid unnecessary over or
      under diagnosis of GORD. Systematic investigation of the contribution of GORD to
      sleep disturbance in infants and young children is warranted.

PMID- 9588642
TI  - Preschool behaviour problems in a multicultural Australian urban area.
AB  - OBJECTIVE: This paper reports on a survey of behaviour problems in a sample of 4
      year-old preschoolers from the western suburbs of metropolitan Melbourne. This
      region consists of a diverse multicultural population and families from lower
      socio-economic status (SES) backgrounds. METHODOLOGY: Nineteen preschools
      participated in the study and information was obtained for 743 preschool children
      (Refer to MS) age=4.7 years). Parents were asked to complete the Preschool
      Behaviour Questionnaire (PBQ) and additional questions referring to demographic
      and family information. Teachers were also asked to complete the PBQ on each of
      the children. Three factors were extracted from the PBQ (anxious-fearful, hostile
      aggressive, hyperactive), and also a combined externalising behaviours factor.
      RESULTS AND CONCLUSIONS: Findings indicated lower levels of behaviour problems in
      this sample compared to that of other Australian studies. Boys showed higher
      rates of externalising behaviour problems than girls. The relationships between
      behaviour problems and language difficulties, ethnicity, and socio-economic
      status are discussed.

PMID- 9588643
TI  - Current approaches to the nutritional management of cystic fibrosis in Australia.
AB  - OBJECTIVE: The aim of this study was to determine current Australian practice for
      the nutritional management of cystic fibrosis (CF) and compare it to USA and UK
      guidelines. METHODOLOGY: A structured questionnaire was completed by dietitians
      from 15 major CF centres. It was estimated that these centres manage or co-manage
      84% of Australians with CF. RESULTS: There was close agreement between UK and USA
      guidelines and Australian practice for dietary intervention strategies,
      nutritional monitoring and surveillance, and electrolyte replacement. Infant
      feeding practices were more closely aligned with the UK. There were some
      differences in the areas of pancreatic enzyme replacement therapy, vitamin
      requirements in CF and dietary management of CF-related diabetes. CONCLUSIONS:
      Despite the lack of formal agreement, nutritional management practices of most
      Australian centres are closely aligned with current published international
      recommendations. However, there is need for consensus in the area of enzyme
      replacement therapy, management of CF-related diabetes and vitamin
      supplementation based on optimal clinical outcomes.

PMID- 9588644
TI  - Documentation of children's vaccination status in child care centres in Victoria.
AB  - OBJECTIVE: To assess the record-keeping of child care centres in Victoria with
      respect to children's vaccination status. METHODOLOGY: A random sample of 113
      centres from a list of over 800 registered Victorian child care centres received
      a mailed questionnaire on characteristics and policies of the centre, including
      documentation of attending children's vaccination status. RESULTS: The response
      rate was 86.7%; more than 95% of centres had children under two in care. Only 85%
      of centres kept any record of children's immunisation status, with smaller
      centres and class 2 centres (occasional care centres) significantly less likely
      to keep records. Records were updated irregularly. Fewer than half of the centres
      studied kept a record of whether children had been vaccinated against Haemophilus
      influenzae type b. CONCLUSIONS: Despite the importance of documenting children's
      vaccination status, many child care centres have failed to develop adequate
      systems to record or update records of children's immunisation. This makes
      exclusion during outbreaks of a vaccine-preventable disease difficult. The
      ongoing process of accreditation may eventually improve performance, but both
      legislation and a better educational strategy to improve practice in this area
      are needed.

PMID- 9588627
TI  - The role of glycoproteins in neural development function, and disease.
AB  - Glycoproteins play key roles in the development, structuring, and subsequent
      functioning of the nervous system. However, the complex glycosylation process is
      a critical component in the biosynthesis of CNS glycoproteins that may be
      susceptible to the actions of toxicological agents or may be altered by genetic
      defects. This review will provide an outline of the complexity of this
      glycosylation process and of some of the key neural glycoproteins that play
      particular roles in neural development and in synaptic plasticity in the mature
      CNS. Finally, the potential of glycoproteins as targets for CNS disorders will be
      discussed.

PMID- 9588645
TI  - Cataracts in insulin-dependent diabetes mellitus: sixteen years' experience in
      children and adolescents.
AB  - OBJECTIVE: To report on cases of diabetic cataracts in a paediatric and
      adolescent population. METHODOLOGY: Medical histories of children and adolescents
      attending the Royal Children's Hospital Diabetes Service who had developed
      cataracts between 1981 and 1996 were examined. RESULTS: Nine cases of diabetic
      cataracts have been managed over the 16-year time frame. Two cases presented at
      diagnosis of insulin-dependent diabetes mellitus (IDDM) and one 3 weeks after.
      The remaining six presented 1.7-13 years (mean 5.17+/-4.02) after diagnosis of
      IDDM. All but one had exhibited poor control of their diabetes with high HbA1C
      values. CONCLUSIONS: Cataracts occurring in the paediatric and adolescent
      population, though uncommon, lead to marked morbidity. It is recommended that all
      children have an ophthalmological examination at diagnosis, particularly if they
      have had a long duration of symptoms before diagnosis. Persistently poor diabetes
      control and/or blurred vision are indications for prompt ophthalmological review.

PMID- 9588646
TI  - The use of medication in children attending childcare in Western Australia.
AB  - OBJECTIVE: This paper reports on medication use and factors affecting use in a
      cohort of preschool children attending long daycare in centres and family daycare
      in homes. METHODOLOGY: A survey of parents representing 846 children under 6
      years old in two types of childcare in Perth, Western Australia. The data were
      analysed using descriptive and logistic regression techniques to elucidate
      factors associated with use of medication. RESULTS: Seventy-three per cent of the
      children were reported to have used over-the-counter medication at some time,
      whilst current regular use of prescribed medication was 11%. This proportion is
      comparable to the limited available data for children of similar ages in Western
      Australia. For both medication categories, the use of medication was higher in
      long daycare than family daycare. In addition, many other characteristics
      differed between children in long daycare and family daycare. Initial analysis
      showed a number of significant associations between child and family factors and
      both categories of medication. Multivariable analyses indicated that the most
      important associations with medication use were with children's illnesses. There
      was no significant difference between long daycare and family daycare for use of
      over-the-counter medication but attending long daycare was significantly
      associated with increased use of prescribed medication (OR=2.13; 95% CI 1.24
      3.67) after illnesses had been taken into account. CONCLUSION: Medication use in
      children attending childcare is closely related to reported illness in the child.

PMID- 9588647
TI  - Shortcomings in psychosocial history taking in a paediatric emergency department.
AB  - OBJECTIVE: To assess the quality of documentation of the psychosocial history
      taken from parents who repeatedly bring their infants and young children to an
      emergency department. METHODOLOGY: We prepared a list of 26 psychosocial items,
      indicated by the literature to be important elements of a history taken in this
      setting. We then reviewed subjects' casenotes, and compared each history to this
      ideal list. PARTICIPANTS/SETTING: Case note review of 104 children under 2 years
      who had presented to a paediatric emergency department at least five times in 1
      year. RESULTS: Documentation of psychosocial history for these subjects was very
      poor, with a mean of only 5 of the 26 possible psychosocial items mentioned per
      set of casenotes. The majority of records lacked important information, including
      basic demographic data. CONCLUSIONS: We canvass possible reasons for poor
      psychosocial history taking, and argue for changes in medical education, the
      development of techniques to efficiently identify at risk children and families,
      and improved resources for referral.

PMID- 9588648
TI  - Streptococcus pneumoniae-induced haemolytic uraemic syndrome.
AB  - Haemolytic uraemic syndrome secondary to infection with neuraminidase producing
      Streptococcus pneumoniae is well recognised, but was previously considered to be
      rare. This case report describes the course of a 9-month-old male with
      pneumococcal pneumonia, T activation and haemolytic uraemic syndrome. The
      clinical features of three other cases treated in Southeast Queensland in the
      past 2 years and 12 previously reported cases are summarised. The widespread
      availability of rapid diagnostic testing for this entity should allow for
      increased recognition, enabling appropriate use of low plasma volume blood
      products with improved patient outcome.

PMID- 9588649
TI  - A cluster of cases of neonatal coxsackievirus B meningitis and myocarditis.
AB  - Three babies were referred with enteroviral meningitis and myocarditis during a 4
      month period. During this same period there was an increased frequency of
      coxsackievirus B type 2 isolates reported to the National Centre for Disease
      Control. Myocarditis was simultaneous with meningitis in one baby, but delayed by
      10 weeks in another, in whom myocarditis mimicked myocardial infarction. Two of
      the three mothers experienced abdominal pain, one with antepartum haemorrhage,
      which has been described previously with coxsackievirus infection in pregnancy.
      Diagnosis was made in two babies by polymerase chain reaction on cerebrospinal
      fluid.

PMID- 9588650
TI  - Bradyarrhythmia and supraventricular tachycardia in a neonate with RSV.
AB  - Respiratory syncytial virus infection is the most common cause of hospital
      admissions in children under 1 year of age. Various cardiac dysrrhythmias have
      been reported to be associated with respiratory syncytial virus infection. We
      report a case where both tachyarrhythmia and bradyarrhythmia occurred within the
      same illness. Paediatricians need to be aware of this association.

PMID- 9588651
TI  - Neurological deterioration following head injury: the eyes had it.
AB  - A 17-year-old male presented with confusion following a mild head injury.
      Repeated CT scans of the head were normal. There was a 3 year history of
      decreased vision, associated with a focal pigmentary retinopathy. On assessment
      he demonstrated visual agnosia and early dementia. An MRI scan showed symmetrical
      demyelination of the white matter, particularly of the occipital lobes. The
      diagnosis of subacute sclerosing panencephalitis (SSPE) was confirmed by the
      typical EEG findings and the presence of measles antibodies in the CSF. The head
      injury was the precipitating factor which led to a diagnosis of SSPE. This
      disease should be considered in young patients who have persisting cognitive
      dysfunction out of keeping with the severity of the initial trauma. A focal
      pigmentary retinopathy, especially with macular involvement, should also raise
      the possibility of SSPE, despite the absence of neurological symptoms initially.
      We report the longest interval to date between the visual symptoms and onset of
      neurological signs of SSPE.

PMID- 9588653
TI  - NHLBI workshop on the utilization of ECG databases: preservation and use of
      existing ECG databases and development of future resources.
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 the
      electrocardiogram (ECG) recorded with digital technology as an inexpensive and
      noninvasive tool for prognosis and diagnosis. Clinicians, epidemiologists, and
      engineers from industry, government, and academic medical centers gathered at a
      workshop sponsored by the National Heart, Lung, and Blood Institute (NHLBI) on
      June 11-12, 1997, to discuss the research potential of ECG databases, their
      preservation and accession, and standards for recording and storage. Databases
      considered were those acquired in ongoing and future NHLBI-funded studies and in
      clinical settings in which the ECG continues to provide valuable information for
      evaluation and treatment. The accessibility of existing databases, the quality of
      their data, and the availability of ancillary demographic and clinical
      information were major themes. Also discussed were appropriate statistical
      methodologies to be used with these data for developing and testing ECG
      algorithms. The workshop participants affirmed the value of these databases and
      urged the establishment of an ECG advisory and review group to (1) resolve
      technical and proprietary issues for the utilization of currently existing
      databases; (2) develop standards for recording, storage, and utilization of ECGs
      in future NHLBI-supported studies; (3) oversee the creation of a national ECG
      database resource, consisting of an archive of ECG databases from past and
      ongoing NHLBI-supported studies, and a registry of ECG databases that would
      eventually include digital ECGs from populations currently underrepresented in
      the demographic spectrum of the NHLBI databases.

PMID- 9588652
TI  - Lead system transformation of body surface map data.
AB  - Multicenter application of body surface map data (multilead electrocardiographic
      [ECG] data) is hampered by the fact that the centers involved in body surface
      mapping use lead systems differing in lead placement as well as in the number of
      leads. In this study, the performance of two methods for converting multilead
      ECGs from one lead system to another is evaluated in their application to the
      major lead systems presently in use throughout the world. The first method is
      based on Laplacian interpolation, and the second method is derived from the
      correlations between the signals in an extensive lead system. Through analyzing
      the representation errors, it was found that, for lead systems incorporating over
      60 leads, both methods work well, yielding errors comparable to interbeat
      differences in individuals. For lead systems incorporating fewer leads, the
      correlation method is to be preferred.

PMID- 9588654
TI  - Prognosis following acute myocardial infarction in patients with ECG evidence of
      left ventricular hypertrophy prior to infarction.
AB  - This study was designed to determine the relationship between prognosis after
      myocardial infarction (MI) and left ventricular hypertrophy (LVH). Left
      ventricular hypertrophy diagnosed by electrocardiography according to the
      criteria of Sokolow and Lyon was noted in 57 of 223 patients (25.6%) on the pre
      MI electrocardiogram (ECG), in 11.2% on an early post-MI ECG, and in 11.3% on the
      discharge ECG. In-hospital and 1-year postdischarge mortalities were
      significantly greater in patients with LVH noted on pre-MI ECG than in patients
      without prior LVH. There was no relationship between the presence of LVH on early
      post-MI ECGs and in-hospital or postdischarge 1-year mortality. Multivariate
      analysis revealed that evidence of LVH on a pre-MI ECG and acute congestive heart
      failure were independent predictors of cardiac death within 1 year of MI in
      patients over 70 years old. It is concluded that in patients over 70 years of
      age, the presence of LVH on a pre-MI ECG is a reliable predictor of post-MI
      prognosis.

PMID- 9588656
TI  - Effect of physical training on QTc interval in elderly people.
AB  - In order to assess whether heart rate-adjusted QT duration (QTc) is reduced by
      physical activity in an elderly population, a randomized, controlled intervention
      study of the effect of a 6-month intensive training program on QTc was
      undertaken. The participants were 229 healthy men and women, aged 60-80 years.
      The subjects of the intervention group trained three to four times a week at a
      work load of about 70% of their maximum capacity for 6 months, while the control
      subjects maintained their habitual activities. The main outcome measures were
      change in QTc and resting heart rate. For women, the mean QTc interval (ms) of
      the intervention group changed by -6.7 (SE 2.8) versus 0.6 (SE 2.4) in the
      control group (P = .05), while for men, the change in the intervention group
      subjects was -2.7 (SE 2.2) versus 0.4 (SE 3.1) in the control subjects (P = .39).
      Also, resting heart rate (beats/ min) changed in intervention group women by -4.6
      (SE 1.7) as against -0.06 (SE 1.1) in the control subjects (P = .02), and in
      intervention group men it changed by -3.2 (SE 1.2) versus -0.9 (SE 1.5) in the
      control subjects (P = .25). These data indicate that regular physical activity
      favorably affects QTc in elderly women. A similar, but not significant, trend was
      observed in men. The beneficial shift in QTc may be caused by a more favorable
      autonomic balance through increased parasympathetic activity. The reduced resting
      heart rate in subjects of the intervention group supports this view. Although the
      reduction was relatively small, it may represent a favorable effect on
      cardiovascular risk.

PMID- 9588655
TI  - Autonomic changes during pregnancy: assessment by spectral heart rate variability
      analysis.
AB  - The aim of this study was to investigate cardiovascular autonomic balance in
      normal pregnancy through spectral analysis of heart rate variability. For this
      purpose, electrocardiograms were recorded in 8 nonpregnant women and in 32
      pregnant women at 10-39 weeks of gestation. Low-/high-frequency peak (LF/HF)
      ratio was used as an indirect index of sympathovagal balance. In left lateral
      recumbency, the LF/HF ratio was lower in pregnant women than in control subjects
      at all gestational ages. The LF/HF ratio was not affected by turning from left
      lateral to supine recumbency in control subjects, whereas it significantly
      increased in pregnant women (eg, from a mean +/- SD of 1.05 +/- 0.81 to 2.18 +/-
      1.69 after the 33rd week of gestation). Handgrip at low intensity remarkably
      increased the LF/HF ratio both in control subjects (from 2.21 +/- 2.76 to 2.73 +/
      1.91) and in pregnant women (from 1.28 +/- 1.17 to 2.24 +/- 0.95 at 34-39 weeks
      of gestation). The results suggest that a rearrangement of autonomic tone takes
      place in normal pregnancy, which could be interpreted either as a shift of
      autonomic balance toward a relative vagal predominance or as the consequence of
      attenuation of baroreflexes.

PMID- 9588658
TI  - Assessing the cause of T wave inversion in precordial leads with ECG mapping.
AB  - Inversion of the T wave in precordial leads in patients with angina pectoris is a
      predictor of coronary disease; however, it may also be seen in normal adults. The
      aim of this study was to assess the cause of T wave inversion by carrying out
      precordial electrocardiographic (ECG) mapping in 51 patients, who also underwent
      echocardiography and coronary angiography. The 37 patients in group A had
      atypical symptoms. They included 11 patients who showed M pattern mapping, of
      whom 7 had noncoronary cardiac disease and 4 were normal. In 23 other group A
      patients, whose mappings were in the N pattern, the angiography was normal. In
      the remaining three patients of this group, mappings were in the I pattern, with
      angiography revealing coronary disease in two of them and no disease in the
      third. The 14 group B patients all had typical angina; mappings were in the I
      pattern in 8 of the patients and in the N pattern in the remaining 6. Angiography
      revealed coronary artery disease in all patients with the I pattern mapping,
      while all those with the N pattern were found to be normal. Sensitivity,
      specificity, and positive predictive value for detecting normal subjects were all
      100% for N pattern mapping; for detecting coronary disease, they were 100%, 90%,
      and 90% for I pattern mapping, respectively. It is concluded that precordial ECG
      mapping is an accurate method for the assessment of T wave inversion in
      precordial leads.

PMID- 9588657
TI  - Effects of the ATP-sensitive K channel opener nicorandil on the QT interval and
      the effective refractory period in patients with congenital long QT syndrome.
      Investigator Group for K-Channel Openers and Arrhythmias.
AB  - Congenital or idiopathic long QT syndrome is characterized by a frequently lethal
      ventricular arrhythmia called torsades de pointes (TdP) as well as a prolonged QT
      interval. The long QT interval related to an abnormal gene of the Na+ channel has
      been shown to be shortened by mexiletine. However, the action of K+ channel
      openers on the QT interval associated with abnormal genes of the K channel has
      yet to be studied. Seven patients of five families with long QT syndrome were
      included in this study, of whom six had syncope and six had documented TdP.
      Either long QT interval or sudden cardiac death had been observed in family
      members of all seven patients. At 1 to 3 weeks after admission, when TdP or
      frequent ventricular arrhythmia had subsided, nicorandil, an ATP-sensitive K
      channel opener, was administered orally at a dose of 15 mg/day in five patients
      and at 30 mg/day in the remaining two patients, and the effects were assessed on
      the third day after drug administration. In four patients, the effective
      refractory period was measured in the right ventricle before and after
      administration of K channel opener administration. The QT interval (QTc) prior to
      administration of the K channel opener was 0.60 +/- 0.09 ms (mean +/- SD) (0.61
      +/- 0.10 second(1/2)), which was shortened to 0.54 +/- 0.05 ms (0.55 +/- 0.06
      second(1/2)) on the third day of drug administration (P < .05 for both): 10.4 +/-
      8.0% (8.6 +/- 5.5%). The QT interval at varying preceding R-R intervals on Holter
      electrocardiograms showed a shift toward the right as a result of the drug
      administration. The effective refractory period showed a significant
      prolongation, 256 +/- 26 ms versus 280 +/- 22 ms before and after drug
      administration, respectively (P <.05). Intravenous administration of nicorandil
      resulted in no significant change in heart rate or blood pressure, while QTc
      showed a tendency to shorten, but nonsignificantly (P = .08). However, a hump on
      the monophasic action potential was abolished, especially at the long preceding R
      R interval induced by premature stimulation of the ventricle. It is concluded
      that nicorandil shortens the QT interval slightly when administered orally,
      whereas the effective refractory period shows a slight prolongation. The
      physiologic and clinical significance of these effects needs to be studied
      further.

PMID- 9588659
TI  - Effect of isoproterenol on QRS complex morphology during ventricular pacing:
      implications for pace mapping.
AB  - Ventricular pace mapping may be used to identify the site of origin of idiopathic
      ventricular tachycardia. Isoproterenol is often required to induce this type of
      ventricular tachycardia, but its effect on QRS morphology during pace mapping is
      unknown. Therefore, this study was performed to evaluate the effect of
      isoproterenol on QRS morphology during ventricular pacing. The study population
      consisted of 20 patients (mean age 38 +/- 14 years) undergoing a clinically
      indicated electrophysiology procedure. Ventricular overdrive pacing was performed
      in trains of 12 stimuli at cycle lengths of 400, 350, 300, and 250 ms, first in
      the baseline state during an infusion of isoproterenol, and again after
      isoproterenol washout. Pacing was performed at the right ventricular apex in 10
      patients, in the right ventricular outflow tract in 6 patients, and in the left
      ventricle in 4 patients. Visual evaluation revealed no apparent effects of
      isoproterenol on QRS morphology at any of the three pacing sites or at any of the
      pacing cycle lengths. It was concluded that QRS morphology during ventricular
      pacing is not affected by isoproterenol infusion. Therefore, in patients with
      idiopathic ventricular tachycardia, even if the induction of tachycardia requires
      infusion of isoproterenol, successful pace mapping may be performed in its
      absence.

PMID- 9588660
TI  - Effects of magnesium sulfate on electrical ventricular defibrillation of dogs.
AB  - Magnesium ion infusion has been reported for treatment of hypomagnesemia often
      associated with myocardial infarction and with surgeries involving
      cardiopulmonary bypass (CPB). Magnesium infusion before CPB has been reported to
      adversely affect the ability to defibrillate after CPB. However, there are also
      reports of magnesium ion infusion facilitating defibrillation of refractory
      ventricular fibrillation. This study evaluated the isolated effect of magnesium
      ion infusion on the shock intensity requirements for electrical defibrillation.
      The electric current required to defibrillate with 50% success (the ED50) was
      estimated in five mongrel dogs at baseline and again after each of four magnesium
      sulfate (80 mg/kg) infusions. The total serum magnesium level increased from 2.32
      +/- 0.08 mg/dL (mean +/- SD) to 7.92 +/- 0.80 mg/dL. The mean estimated ED50
      decreased from 12.8 +/- 2.9 A at baseline, to 11.1 +/- 0.8 A after the fourth
      infusion (P < .05), decreasing the delivered energy by 25%. Magnesium sulfate
      infusion was associated with a significant decrease in the electrical
      requirements for defibrillation. Key words: magnesium, electrical ventricular
      defibrillation.

PMID- 9588661
TI  - Mechanism of atrial escape-capture bigeminy: second-degree sinoatrial exit and
      entrance block.
AB  - Two women with atrial escape-capture bigeminy were reported in whom sinus P waves
      and escape P waves alternated with each other. Their electrocardiographic
      findings showed that, during the bigeminal rhythm, 2:1 exit block of sinus
      impulses associated with entrance block of escape impulses occurred in the
      sinoatrial junction. Three phenomena are suggested to explain the observations.
      (1) Seeming bradycardia-dependent sinoatrial exit block may have occurred,
      probably as a result of phasic changes in vagal tone due to respiration, with
      decreased vagal tone depressing conductivity in the sinoatrial junction to a
      greater degree than automaticity in the sinus node. (2) In case 1, type II second
      degree entrance block in the sinoatrial junction may have occurred, reflecting
      the presence of sinus parasystole with incomplete entrance block. (3) Sinus
      escape also may have occurred, especially in case 2. These phenomena have never
      been reported before.

PMID- 9588662
TI  - Apparent bradycardia-dependent block in the accessory pathway in intermittent
      Wolff-Parkinson-White syndrome.
AB  - A case of intermittent Wolff-Parkinson-White syndrome is reported, which is the
      first report of an apparent bradycardia-dependent block in the accessory pathway.
      When the P-P interval gradually lengthened to a critical value of 0.89 second or
      more, preexcitation failed to occur, but thereafter, when the P-P interval
      gradually shortened to 0.89 second or less, preexcitation again occurred. These
      findings seem to suggest that bradycardia-dependent block occurred in the
      accessory pathway. In the electrocardiogram taken on another day, however, when a
      ventricular extrasystole was followed by a compensatory pause, the ensuing QRS
      complex showed preexcitation, although the pause was markedly longer than the
      critical period of 0.89 second. This indicates that this case is not one of true
      bradycardia-dependent block in the accessory pathway. Rather, the effect occurred
      because increased vagal tone depressed conductivity in the accessory pathway to a
      greater degree than automaticity in the sinus node.

PMID- 9588663
TI  - Prediction of functional recovery in acute myocardial infarction: comparison
      between sestamibi reverse redistribution and sestamibi/BMIPP mismatch.
AB  - BACKGROUND: It has been known that Tc 99m sestamibi/iodine 123
      betamethyliodophenylpentadecanoic (123I-BMIPP) (sestamibi/BMIPP) mismatch is an
      indicator of viable myocardium in acute myocardial infarction (AMI). We have
      reported that reverse redistribution of sestamibi in AMI indicates the patency of
      infarct-related artery and a preserved left ventricular function in the chronic
      stage. In this study we investigated the relationship between reverse
      redistribution of sestamibi and sestamibi/BMIPP mismatch in patients with AMI.
      METHODS: Twenty-three patients with AMI who received direct percutaneous
      transluminal coronary angioplasty underwent both BMIPP and sestamibi SPECT within
      2 weeks after onset. Sestamibi images were obtained 1 hour (early) and 3 hours
      (delayed) after injection of sestamibi. BMIPP imaging was carried out 30 minutes
      after injection. The left ventricle was divided into 17 segments, and regional
      myocardial uptakes of the tracers in each segment were scored from 0 (normal) to
      3 (no activity). A reverse redistribution pattern was defined as an increase of >
      or =1 in the regional score at the delayed images. More reduced BMIPP uptake than
      sestamibi uptake in each segment was determined as sestamibi/BMIPP mismatch.
      Contrast left ventriculography was performed soon after revascularization and
      repeated 1 month later. RESULTS: Of 15 patients with sestamibi reverse
      redistribution, sestamibi/BMIPP mismatch was observed in 14 patients (93%),
      whereas mismatch was seen in only one of seven patients (14%) without reverse
      redistribution (p < 0.01). In patients with sestamibi reverse redistribution,
      regional scores of BMIPP agreed with those of early and delayed images of
      sestamibi in 51 segments (46%) and in 92 segments (83%), respectively. In the
      chronic stage, both regional wall motion and left ventricular ejection fraction
      improved in patients with sestamibi reverse redistribution (wall motion score:
      6.7 +/- 2.4 vs 2.7 +/- 2.1, p < 0.01; ejection fraction: 56% +/- 7% vs 64% +/-
      8%, p < 0.01), but not in those without reverse redistribution. CONCLUSION: Both
      reverse redistribution of sestamibi and sestamibi/BMIPP mismatch reflect the
      recovery of left ventricular function and thus imply myocardial viability in AMI.
      Because the presence of reverse redistribution of sestamibi agreed with that of
      sestamibi/BMIPP mismatch, additional BMIPP images can be replaced by the delayed
      images after a single injection of sestamibi.

PMID- 9588665
TI  - Theoretical model for myocardial functional characterization: application to a
      group of patients evaluated before and after surgical revascularization.
AB  - BACKGROUND: The functional improvements resulting from coronary revascularization
      (CABG) in patients with depressed ventricular function may be described by the
      use of a model combining global or local quantification of myocardial perfusion,
      viability, and contraction. An illustration of this model, with data provided by
      conventional radionuclide studies as they are performed routinely in many
      centers, is presented and the limitations of this approach for predicting the
      results of CABG are discussed. METHODS AND RESULTS: The model is based on three
      independent variables, which can be approximated in this preliminary study by
      parameters derived from standard stress and redistribution/reinjection thallium
      201 single-photon emission computed tomography (SPECT) acquisitions with
      quantification of the tracer uptake defects and from a planar gated blood pool
      left ventricular ejection fraction (LVEF) measurement: Perfusion is assumed to
      correspond to 100-stress defect (in percentage), viability is 100
      redistribution/reinjection defect, and contraction is 100(LVEF/70), assuming that
      a normal 70% LVEF corresponds to 100% contraction. In a group of 30 patients
      prospectively evaluated with this protocol and included in the study on the basis
      of a pre-CABG LVEF <40%, a significant improvement in LVEF was demonstrated
      (28.2% +/- 8.5% before CABG vs 35.8% +/- 7.3% after CABG), which is accompanied
      by a significant decrease of the stress thallium defects (34.8% +/- 13.8% vs
      25.6% +/- 10.6%), whereas the average (but not the individual)
      redistribution/reinjection defects remain almost stable (27.7% +/- 10.9% vs 25.7%
      +/- 10.1%). As reported in the three-dimensional model, pre-CABG and post-CABG
      representative points clearly demonstrate the functional improvements for the
      main variables, but there is a large spectrum of responses to revascularization.
      It appears that the border between reversible and nonreversible thallium defects
      does not match the limit between ischemic myocardium (with no contraction
      alteration and therefore without contraction improvement potential) and
      hibernating myocardium, which is able to recover mechanical function and
      therefore is responsible for the improvement of global LVEF. CONCLUSIONS:
      Thallium SPECT is far from ideal for use as an independent characterization of
      perfusion and viability because hibernating myocardium may be present in both the
      fixed and reversible parts of thallium defects. Prediction of functional recovery
      is conditioned by an accurate identification of viable but underperfused and
      noncontracting myocardium. In the future, with the use of adequate study
      protocols that are able to measure viability without interference of perfusion
      and perfusion independent of viability, the proposed model may be able to
      characterize regional function as a cluster of representative points for each
      territory and to delineate areas of the theoretical volume corresponding to a
      potentially recoverable situation.

PMID- 9588664
TI  - Acute oral trimetazidine administration increases resting technetium 99m
      sestamibi uptake in hibernating myocardium.
AB  - BACKGROUND: Trimetazidine is an antiischemic drug protecting the myocardium from
      ischemic damage through the preservation of mitochondrial oxidative metabolism,
      without any hemodynamic effect. 99mTc-sestamibi is accumulated by myocytes
      according to mitochondrial function. As mitochondrial metabolism is thought to be
      present in hibernating myocardium, the aim of the study was to investigate
      trimetazidine effects on infarcted and eventually hibernating myocardial areas by
      means of 99mTc-sestamibi perfusional scintigraphy, comparing them to
      postoperative recovery of wall motion. METHODS AND RESULTS: Twelve patients with
      previous myocardial infarction underwent 2 perfusion imaging tomographic studies
      at rest with 99mTc-sestamibi, receiving placebo or trimetazidine (60 mg orally),
      and subsequently underwent revascularization procedures. An echocardiographic
      study was carried out before and >3 months after revascularization. At polar map
      analysis of placebo scan, infarcted vascular territories (wall motion score
      index: 2.65 +/- 0.31) showed 73.7% +/- 10.4% of the territory with activity <2.5
      SD from the mean of normals, for a severity (expressed as the sum of the standard
      deviations below average normal values in all abnormal pixels) of 833.8 +/-
      345.7. Polar map analysis of the trimetazidine scan showed tracer uptake
      increased significantly in 11 of them, by 8.2% +/- 3.0% (p < 0.001) and by 180.3
      +/- 111.0 SD (p < 0.001), respectively. Postoperative wall motion score index
      improved significantly in 9 of these territories (-0.9 +/- 0.4, p < 0.001).
      CONCLUSIONS: Trimetazidine-associated increase in 99mTc-sestamibi uptake in
      infarcted but viable myocardial areas is probably related to an improvement in
      mitochondrial oxidative metabolism that is essential to 99mTc-sestamibi
      retention. Additionally, coupling trimetazidine administration to 99mTc-sestamibi
      perfusional scintigraphy may represent a means of detecting viable myocardium.

PMID- 9588666
TI  - An investigation of the estimation of ejection fractions and cardiac volumes by a
      quantitative gated SPECT software package in simulated gated SPECT images.
AB  - BACKGROUND: The purpose of this investigation was to determine the accuracy of
      the estimation of ejection fractions (EFs) and left ventricular volumes from a
      commercially available software package (Quantitative Gated SPECT [QGS]) as a
      function of different true EFs, count level in the acquisitions, severity and
      location of perfusion defects, increasing hepatic activity, and modified wall
      motion. METHODS AND RESULTS: The dynamic mathematic cardiac-torso digital phantom
      was used to create three-dimensional source and attenuation maps representing the
      distribution of a technetium-99m-labeled cardiac perfusion agent in the chest.
      Three hearts with varying end-systolic volumes were used to investigate different
      EFs. Perfusion defects were created as localized uptake within selected portions
      of the cardiac walls, scaled to the desired fraction of the normal wall uptake,
      and subtracted from the normal distribution. The hepatic uptake was increased up
      to five times of the normal heart uptake to investigate the influence of a "hot"
      liver. Alteration of lateral wall motion was also investigated. A three
      dimensional projector that included the influence of distance-dependent spatial
      resolution and nonuniform attenuation was then used to create projection images.
      The projections were scaled to the desired acquisition count level, and Poisson
      noise was added. Automatic determination of EF slightly overestimated the true EF
      for normal count levels by 3% to 7% of the true EF and underestimated the true EF
      by up to 9% for very low count levels for 180-degree reconstructions. The
      accuracy for determining the volumes was not as high as for the EFs (an average
      error of 12% was observed). The calculated EFs were relatively accurate for
      perfusion defects of 50% or less. When perfusion defects exceeded 50%,
      extracardiac counts were included in the heart contours, causing larger
      underestimations of EF. With removal of the extracardiac counts, the EFs
      increased. With a hepatic uptake of two or more times the heart uptake, no
      meaningful EF could be obtained. Either drawing a single region of interest for
      every slice or use of the manual mode with constrain option could remarkably
      improve the estimation. The accuracy of the calculation of EF and volumes for the
      heart with stationary wall was fairly high but decreased significantly when
      coupled with perfusion defects. CONCLUSION: It is concluded that the QGS program
      evaluates the functional parameter of EF accurately. The biggest limitations
      occurred in determining the appropriate cardiac contour if areas with very high
      extracardiac counts were present in the heart slices, and when a greater than 50%
      decrease occurred in uptake for perfusion defects.

PMID- 9588667
TI  - Effects of myocardial revascularization on regional thallium-201 uptake and
      systolic function in regions with reverse redistribution on tomographic thallium
      201 imaging at rest in patients with chronic coronary artery disease.
AB  - OBJECTIVES: There is growing evidence that myocardial segments with reverse
      redistribution are viable in patients with chronic coronary artery disease. The
      aim of this study was to assess the effects of myocardial revascularization on
      systolic function and thallium-201 uptake in such segments. METHODS: Rest
      redistribution thallium-201 tomography before and after myocardial
      revascularization was performed in 47 patients with chronic coronary artery
      disease. Regional function was evaluated by two-dimensional echocardiography
      before and after revascularization according to a 3-point scale (1 = normal, 2 =
      hypokinetic, 3 = a/dyskinetic). Improvement of dysfunctional segments was defined
      when systolic function score decreased > or =1 after revascularization. Reverse
      redistribution was defined as >8% decrease in relative thallium-201 uptake
      between rest and redistribution images. RESULTS: Reverse redistribution was found
      in 27 (57%) of 47 patients, corresponding to 60 (11%) of 564 myocardial segments.
      Of such segments, 24 (40%) had normal systolic function, 19 (32%) were
      hypokinetic, and 17 (28%) were a/dyskinetic. Thirty-six segments underwent
      myocardial revascularization, and reverse redistribution was no longer present in
      86% of them subsequent to the procedure. Of 26 dyssynergic segments with reverse
      redistribution subjected to revascularization, 18 (69%) improved at follow-up.
      CONCLUSIONS: The findings of the present study indicate that reverse
      redistribution is a reversible phenomenon and is often associated with
      improvement of systolic function following revascularization in patients with
      chronic coronary artery disease.

PMID- 9588668
TI  - An optimal dual-size vial system for the cost-effective usage of Adenoscan.
AB  - BACKGROUND: Adenoscan (Fujisawa USA, Inc., Deerfield, Ill.) has been initially
      packaged in a 30 ml glass vial for single use only because it contains no
      preservative. This restricted usage has generated considerable waste and high
      cost for the patient. Although the new 20 ml vial of Adenoscan provides some
      reduction in waste, the savings offered by the 20 ml and 30 ml vial system is
      still not optimal. The purpose of this study was to investigate an optimal dual
      size vial system that would provide limited amounts of waste while maintaining
      its practicality to satisfy different patient populations. MATERIALS AND RESULTS:
      The least waste for each potential combination (n = 344) of two vials was
      calculated by assuming that patient weights (30 to 200 kg) follow a normal
      distribution. The 6 ml and 15 ml vial combination had the least expected waste
      for lighter patient populations, and the 9 ml and 15 ml vial system had the least
      expected waste for heavier populations. The calculated wastes for 4207 patients
      (83 +/- 19 kg) undergoing adenosine stress myocardial perfusion studies at the
      Mayo Clinic were 10.5 +/- 9.3 ml (30 ml vial), 5.1 +/- 2.9 ml (20 ml and 30 ml
      vial system), 1.6 +/- 1.0 ml (6 ml and 15 ml vial system), and 1.8 +/- 1.2 ml (9
      ml and 15 ml vial system). CONCLUSIONS: In general, both the 6 ml and 15 ml and 9
      ml and 15 ml vial systems perform better than either the single 30 ml vial or the
      20 ml and 30 ml vial system. Furthermore, the 6 ml and 15 ml vial combination
      offers the lowest expected waste for the actual patient population that underwent
      the adenosine stress myocardial perfusion imaging studies at our institution.

PMID- 9588670
TI  - Molecular biology for the nuclear cardiologist: terminology, concepts, and
      processes.

PMID- 9588669
TI  - Experimental evaluation of radiotracers: role of intact biological models.

PMID- 9588672
TI  - On myocardial perfusion, metabolism, and viability.

PMID- 9588671
TI  - Reverse redistribution: is it clinically relevant or a washout?

PMID- 9588673
TI  - Methodology of a novel myocardial viability protocol.

PMID- 9588674
TI  - Nuclear cardiology in a managed care environment.
AB  - Health maintenance organizations (HMO) and nuclear cardiology represent mutual
      threats and mutual opportunities for each other. On the one hand, nuclear
      cardiology represents a cost center with HMOs exerting tremendous financial
      pressure on nuclear cardiology programs. On the other hand, nuclear cardiology
      can act as a sage gatekeeper to the cardiac catheterization laboratory and help
      HMOs effectively control the health care of an increasing percentage of the
      population. Through the process of negotiation, of determining each other's
      needs, an accommodation can take place between the two. The ability to correlate
      scan results with coronary angiography provides individual nuclear cardiology
      programs with the opportunity to demonstrate their accuracy. A Nuclear Cardiology
      Report Card based on these data can be developed for use, with HMOs creating the
      opportunity to compete not only on price but also on value. Carved out capitation
      rates for nuclear cardiology can be estimated on the basis of actual experience
      with an HMO population and by extrapolation from test frequency of the U.S.
      population. The financial disincentives of capitation and of managed care
      challenge the physician-patient relationship. Advocacy of the role of nuclear
      cardiology and an understanding of negotiation strategies can aid nuclear
      cardiologists in their attempts to provide quality care with commensurate
      compensation.

PMID- 9588677
TI  - Use of exercise myocardial perfusion imaging to guide and assess the
      effectiveness of medical therapy in coronary artery vasospasm.

PMID- 9588676
TI  - American College of Cardiology policy statement on nuclear cardiology services.

PMID- 9588678
TI  - Nuclear cardiology in the literature.

PMID- 9588675
TI  - Nonperfusion applications in nuclear cardiology: report of a task force of the
      American Society of Nuclear Cardiology.

PMID- 9588679
TI  - In utilizing a technetium 99m perfusion agent, are most laboratories imaging rest
      first and stress later, or the reverse?

PMID- 9588680
TI  - Testicular hormones do not regulate sexually dimorphic Pavlovian fear
      conditioning or perforant-path long-term potentiation in adult male rats.
AB  - We recently reported that Pavlovian fear conditioning and hippocampal perforant
      path long-term potentiation (LTP) are sexually dimorphic in rats. Males show
      greater contextual fear conditioning, which depends on the hippocampus, as well
      as greater hippocampal LTP. In order to examine the role of circulating gonadal
      hormones in adult male rats, animals were castrated in two experiments, and
      Pavlovian fear conditioning and in vivo perforant-path LTP were examined. It was
      found that sexually-dimorphic LTP and fear conditioning are not regulated by the
      activational effects of testicular hormones in adult male rats. That is, in every
      respect, castrated male rats were similar to intact male rats in Pavlovian fear
      conditioning and hippocampal LTP. It is likely that sexual dimorphism in this
      system is established earlier in development by the organizational effects of
      gonadal hormones.

PMID- 9588681
TI  - (-)-Norpseudoephedrine, a metabolite of cathinone with amphetamine-like stimulus
      properties, enhances the analgesic and rate decreasing effects of morphine, but
      inhibits its discriminative properties.
AB  - Like psychomotor stimulants, a weak amphetamine-like agent, such as
      phenylpropanolamine, enhances the analgesic effects of morphine (MOR). Thus, it
      is possible that full psychomotor stimulant potency is not required to increase
      the analgesic action of opiates. The validity of this assumption is here tested
      by studying the ability of (-)-norpseudoephedrine (NPE), an enantiomer of
      phenylpropanolamine and a metabolite of cathinone, to influence both the
      analgesic effects of MOR and its discriminative stimulus properties. In mice NPE
      (5.6-10.0-17.0 mg/kg i.p.) did not prolong the latency to lick or to remove paws
      from a plate warmed at 54 degrees C. However, it significantly potentiated the
      analgesic effect of 3.2 mg/kg of MOR. These results were replicated in rats by
      use of the formalin test, which measures the numbers of hind paw flinches
      produced by injecting 50 microl of formalin into the dorsal surface of the paw.
      The higher dose of NPE (17 mg/kg) increased the effect of sub-analgesic doses of
      MOR (0.56 and 1.0 mg/kg). In rats trained to discriminate between 0.5 mg/kg of
      amphetamine and solvent in a two-lever operant behavior reinforced by water
      access. NPE induced a dose-dependent increment of drug lever responding from 0%
      at 1.0 mg/kg to 100% at 32.0 mg/kg. In contrast, NPE did not generalize for the
      MOR cue up to the dose of 56.0 mg/kg, which produced a substantial reduction of
      the response rate. However, when given in combination, NPE attenuated the
      discriminative effects of MOR and potentiated its inhibitory action on the
      response rate. These results exclude a direct action of NPE on the mu opiate
      system. In conclusion, NPE preserves amphetamine-like properties and these
      properties are probably responsible for the interaction of the drug with the
      analgesic and discriminative effects of MOR. Therefore, this study contradicts
      the assumption that the analgesic effects of MOR can be enhanced by a
      sympathomimetic drug that lacks significant psychostimulant actions.

PMID- 9588683
TI  - Heterogeneity of the hippocampus: effects of subfield lesions on locomotion
      elicited by dopaminergic agonists.
AB  - Structural abnormalities in the hippocampal formation and overactive dopamine
      neurotransmission in the ventral striatum are thought to be key pathologies in
      schizophrenia. This experiment examined the functional contribution of different
      hippocampal subfields to locomotion elicited by D-amphetamine (0.32-3.2 mg/kg)
      and the direct agonists quinpirole (0.025-0.5 mg/kg) and SKF 38393 (2.5-15.0
      mg/kg). Male rats served as unoperated controls or received one of six different
      lesions (hippocampal formation, fimbria-fornix, subiculum, CA3-4, entorhinal
      cortex or dentate gyrus (DG)). The main results indicated that extensive ibotenic
      acid-induced lesions of the hippocampal formation, or colchicine-induced lesions
      of the DG enhanced locomotion elicited by the D2 agonist quinpirole. Electrolytic
      lesions of the fimbria-fornix, in comparison, had much larger effects and
      resulted in increases in the locomotor response to amphetamine and quinpirole.
      These results extend previous demonstrations of hippocampal modulation of the
      ventral striatum by showing that this modulatory influence is dependent on both
      the location and total extent of cell loss within the hippocampal formation. The
      results are discussed in relation to the causes of and neurophysiological
      mechanisms involved in enhanced drug-induced locomotion and in terms of their
      implications for mental diseases including schizophrenia.

PMID- 9588682
TI  - Unilateral hippocampal lesions in newborn and adult rats: effects on spatial
      memory and BDNF gene expression.
AB  - Subcortical damage at birth often produces more severe deficits than similar
      lesions in an adult. In the present study, effects of unilateral electrolytic
      hippocampal ablations made on postnatal day 1 or in 3-month-old adult rats, were
      compared. Exploratory behavior and spatial navigation in the Morris water maze
      (MWM) were assessed 8 and 20 weeks after hippocampal damage. Rats with neonatal
      damage did not respond to novelty in the environment and did not learn to find
      the hidden platform in the MWM. Rats lesioned as adults did learn the water maze
      task, but slower than controls. We hypothesized that behavioral deficits observed
      in rats lesioned at birth, may be due, in part, to neurochemical dysfunction of
      the contralateral hippocampus. Specifically, cholinergic and GABAergic
      neurotransmission were assessed by measuring choline-acetyltransferase (ChAT) and
      GABAdecarboxylase (GAD) activity. In addition, nerve growth factor (NGF) and
      brain-derived neurotrophic factor (BDNF) mRNA levels were assayed in the
      remaining (contralateral) hippocampus. Of these molecules, only BDNF gene
      expression was significantly reduced (by 30%) at 8 and 20 weeks after neonatal
      and adult unilateral ablation. The similar reduction in BDNF mRNA in both
      treatment groups does not correspond with the lesion's differential effect on
      memory function. However, the more severe learning impairment after neonatal
      lesion may reflect increased dependence on trophins during development.

PMID- 9588684
TI  - Ontogenesis of lateralized rotational behavior in hamsters: a time series study.
AB  - This is a longitudinal study of the postnatal development of lateralized
      rotational behavior. Hamsters (n = 75) were tested for spontaneous rotational
      behavior in cylindrical arenas, from P2 (P1 = day of birth) to P60. A daily
      laterality index was calculated for each animal, of which the averages and
      standard deviations were used to follow the animals' lateralized behavior. A
      strong variability between and within animals appeared throughout development,
      with a tendency to the right side in most animals, which declined after the first
      postnatal week. No oscillatory cycles were identified. To study patterns of
      development, the series were divided into four periods and the animals were
      separated into five groups. The laterality indexes of all four periods were
      significantly different between the groups. A total of 79% of the animals showed
      consistent behavior along development: either a preference to one side (20% left,
      26% right), or no preference at all (33%). The remaining animals changed
      preference during development. Only a few animals remained strongly lateralized
      throughout the 60 days, most of them showing a slight, non-significant preference
      after P10. Results suggest an ontogenetic decrease in lateralization of this
      behavior that could in part be explained by the maturation of an interhemispheric
      regulatory system.

PMID- 9588685
TI  - Lesions of the hippocampus or fornix do not interfere with the relative validity
      effect on a discrete stimulus or the context.
AB  - Two experiments with rats used an appetitively motivated instrumental
      discrimination procedure to examine whether damage to the hippocampal system
      would interfere with the relative validity effect in which a partially reinforced
      stimulus trained in compound acquires a weak conditioned response when
      concurrently trained CSs are perfect predictors of the presence or absence of the
      US [A.R. Wagner, F.A. Logan, K. Haberlandt, T. Price, Stimulus selection in
      animal discrimination learning, J. Exp. Psychol. 76 (1968) 171-180]. The true
      discrimination (TD) group received training with two compound cues containing a
      common element. One compound was reinforced and another never reinforced (AX+, BX
      ). Following TD training the common element (X) failed to acquire a strong
      conditioned response in comparison to a control, pseudo discrimination (PD) group
      (AX+/-, BX+/-), in which both compound cues were reinforced 50% of the time.
      Although (X) was reinforced on a partial reinforcement schedule, (50%) in both
      groups, conditioning of X was affected by the reinforcement schedules of the
      accompanying elements (A and B). Neither radio-frequency lesions of the fornix
      fimbria (Experiment 1) nor neurotoxic lesions of the hippocampus (Experiment 2)
      interfered with this effect on X or on the same effect found during the inter
      trial interval (ITI). Rates of ITI responding were higher in the PD groups than
      in the TD groups suggesting stronger contextual conditioning following PD
      training. Furthermore, disruptions to the hippocampal system in Experiment 2
      resulted in increased rates of lever pressing for food. These results do not
      support the notion that the hippocampus is critically involved in selective
      associations.

PMID- 9588686
TI  - Cocaine conditioning and cocaine sensitization: what is the relationship?
AB  - With repeated cocaine use, cocaine conditioned behavior develops to associated
      stimuli, and in addition, sensitization can occur to the unconditioned stimulant
      effects of cocaine. To investigate the relationship between the conditioned and
      unconditioned behavioral effects of repeated cocaine use, two groups of rats (n =
      7) were given five daily paired cocaine treatments (10 mg/kg i.p.) immediately
      before a 20-min placement in an open-field environment. Other groups received
      either saline before testing or cocaine unpaired which was administered 30 min
      after testing in the homecage. When tested in the open-field with saline for
      conditioned effects, the two cocaine paired groups selectively exhibited
      substantial and equivalent cocaine conditioned responses. One of these groups was
      subjected to an extinction procedure which was effective in eliminating the
      cocaine conditioned responses. Subsequently, all the rats which had received
      cocaine in the first phase of the experiment, paired and unpaired, along with a
      subset of saline animals were given a cocaine (10 mg/kg i.p.) challenge test. The
      paired cocaine animals exhibited an earlier onset of the cocaine induced
      behavioral response (sensitization) as compared with the saline and the unpaired
      cocaine animals. Critically, the sensitization effects were unaffected by
      extinction, and in addition, the conditioned response did not contribute to the
      sensitization effect. It is suggested that the cocaine drug response occludes the
      cocaine conditioned response. Subsequent to this sensitization test, the animals
      were retested for conditioning. In this test, the paired cocaine animals which
      had not been subjected to the extinction procedure still exhibited a conditioned
      cocaine response, whereas, the paired cocaine group subjected to extinction was
      indistinguishable from saline controls. Although the present results show that
      Pavlovian conditioned responses to exteroceptive contextual cues do not directly
      contribute to cocaine induced behavioral sensitization effects, the sensitization
      effects were context-specific, and therefore, were tied to associative processes.
      It is suggested that context specificity is mediated by a compound stimulus
      complex comprised of exteroceptive stimuli and interoceptive cocaine drug cues.
      Furthermore, these exteroceptive and interoceptive cues associated with cocaine
      effectively expedite the onset of cocaine effects, and thereby, facilitate the
      addictive potency of cocaine.

PMID- 9588687
TI  - Opposite rotation induced by dopamine agonists in rats with unilateral lesions of
      the globus pallidus or substantia nigra.
AB  - Normal rats with a unilateral ibotenic acid lesion of substantia nigra pars
      reticulata (SNR, n = 12) or globus pallidus (GP, n = 12) were challenged
      systemically with the mixed dopaminergic agonist apomorphine (0.5 and 1.5 mg/kg)
      and the indirect acting d-amphetamine (1.5 mg/kg). The low dose of apomorphine
      produced a weak contralateral rotation only in the SNR-lesioned group, which
      showed an intense ipsilateral rotation following the administration of the higher
      dose. GP-lesioned rats also showed ipsilateral rotation after the high dose of
      apomorphine. d-Amphetamine produced ipsilateral rotation in GP-lesioned rats,
      contrasting with a vigorous contralateral rotation in SNR-lesioned rats. The
      unexpected opposite rotation after apomorphine and d-amphetamine, observed only
      in SNR-lesioned animals, indicates that the role of SNR in basal ganglia
      functions is less clear and more complex than what is expected from our current
      model of basal ganglia circuitry and functions. On the other hand, the GP lesion
      resulted in a consistent and predictable ipsilateral rotation after both
      apomorphine and d-amphetamine, indicating a more determinant effect on the output
      of the basal ganglia than heretofore believed. Our results may contribute to the
      recently expressed views challenging the established model of basal ganglia
      organisation.

PMID- 9588688
TI  - Differences in acquisition and full performance in skilled forelimb use as
      measured by the 'staircase test' in five rat strains.
AB  - Skilled forelimb use was examined in five different rat strains (DA/Ztm, LEW/Ztm
      ci, LEW.1W/Ztm, SD/Ztm, SPRD/Ztm-Cu3) by means of the 'staircase test', as
      originally described by Montoya et al. [20] (C.P. Montoya, H.L. Campbell, K.D.
      Pemberton, S.B. Dunnett, The 'staircase test': A measure of independent forelimb
      reaching and grasping abilities in rats, J. Neurosci. Methods 36 (1991) 219-228).
      Strain-dependent differences were observed most prominently during the
      acquisition phase, and less pronounced, at the full performance level. SD/Ztm and
      DA/Ztm rat strains seemed to be particularly skilled in their forelimb use,
      although with varying levels of activity. Interestingly, significant differences
      in skilled forelimb movements were found between the related Sprague-Dawley
      derived and Lewis congenic rat strains. No clear-cut correlation was found
      between skilled forelimb use and basic nutrition-dependent measures, such as
      pretest body weight or weightloss during the test period. Based on previous
      observations on strain-dependent behavioral variations it seems likely that the
      differences in skilled forelimb use, as observed in the present study, might be
      caused by morphological and/or functional strain-dependent alterations in the
      involved neuronal circuitries, such as motor cortex, caudate-putamen unit and
      mesotelencephalic dopamine system. However, they should also be considered as
      potentially influencing parameters in studies related to the behavioral effects
      of lesions and restorative therapies in the central nervous system.

PMID- 9588689
TI  - Morphine analgesia in the formalin test: reversal by microinjection of quaternary
      naloxone into the posterior hypothalamic area or periaqueductal gray.
AB  - Bilateral microinjection of 5 nmol morphine into the posterior hypothalamic area
      (PHA), periaqueductal gray matter (PAG) or ventral tegmental area (VTA) elicits
      powerful suppression of nociceptive behaviors in the formalin test, an animal
      model of injury produced pain. The object of the present study was to determine
      whether analgesia in the formalin test (50 microl 2.5% formalin injected s.c. in
      one hindpaw) induced by systemically administered morphine requires opioid action
      at these sites, or other putative sites of opioid action. Morphine sulphate (6
      mg/kg s.c.) produced almost complete analgesia in the second phase of the
      formalin test (30-50 min after formalin). Bilateral microinjection of the
      quaternary opioid antagonist naloxone methobromide (NxBr, 28 ng in 0.5 microl, 22
      min after morphine) into the PHA completely abolished morphine analgesia, while
      NxBr into PAG partially reversed analgesia. Microinjection of NxBr into the VTA,
      central nucleus of the amygdala, habenula, striatum, nucleus accumbens or
      hypothalamic sites outside the PHA did not antagonize morphine analgesia,
      although microinjections into some of these sites appeared to reduce the
      cataleptogenic effects of morphine. The data indicate that the PHA and PAG are
      probably the primary sites of action of morphine in the formalin test.

PMID- 9588690
TI  - Evidence for a role of bradykinin neurons in the control of gonadotropin
      releasing hormone secretion.
AB  - The present study provides evidence of a novel neuronal pathway for the control
      of GnRH secretion involving bradykinin neurons. Bradykinin neurons were shown by
      immunohistochemistry to be densely localized in several regions of the brain
      including the cortex, hippocampus and supraoptic nucleus, as well as two regions
      critical in the control of GnRH secretion, the organum vasculosum of the lamina
      terminalis and arcuate nucleus. Bradykinin dose-dependently stimulated GnRH
      release from male and proestrous female rat hypothalami in vitro. Antagonist
      studies revealed that bradykinin effects are mediated by the bradykinin B2
      receptor. The effect of bradykinin on GnRH release is not mediated by the
      classical major transmitter, glutamate, as glutamate antagonists had no effect on
      bradykinin stimulation of GnRH release. Rather, bradykinin appears to act
      directly on the GnRH neuron as bradykinin stimulated GnRH release directly from
      immortalized GnRH (GT1-7) neurons in vitro, and immunoblot studies revealed that
      the bradykinin B2 receptor is present in GT1-7 neurons. The bradykinin B2
      receptor was also demonstrated in the rat hypothalamus and pituitary by
      immunoblotting. Bradykinin-induced exocytosis of GnRH appears to involve
      activation of the PKC signaling pathway, as a PKC inhibitor blocked bradykinin
      induced GnRH release. Finally, bradykinin neurons appear to be important
      mediators of steroid signals in the hypothalamus to produce the LH surge, as
      central administration of a B2 antagonist, but not a B antagonist, significantly
      attenuated the steroid-induced LH surge in the ovariectomized female rat.

PMID- 9588691
TI  - Increase of gonadotropin-releasing hormone concentration in pituitary portal
      blood after substance P administration in male rats.
AB  - Substance P (SP) affects gonadotropin release from the anterior pituitary gland.
      In the present study we tested whether SP exerts this effect through GnRH release
      into pituitary portal blood in intact male rats (INT), orchidectomized rats with
      s.c. chronically implanted empty Silastic capsule (ORCX), testosterone capsule
      (ORCX + T), and 17beta-estradiol capsule (ORCX + E2). The pituitary glands were
      exposed by the transpharyngeal approach under urethane-chloralose anesthesia.
      Then, the stalk portal vessels were cut and three 30-min portal blood samples
      were collected. Each first sample of blood was treated as a control before 0.2 ml
      injection of normal saline, 5 microg, or 25 microg of SP in 0.2 ml of normal
      saline into the internal carotid artery. GnRH concentration in the purified
      portal plasma were measured by RIA. Injection of SP into the internal carotid
      artery caused a significant increase in GnRH concentration in pituitary portal
      plasma only in INT rats. The higher dose of SP markedly increased GnRH
      concentration in the 1st blood sample (p < 0.001) and in the 2nd blood sample
      GnRH concentration was lower but still significant higher than prior SP injection
      (p < 0.05). The lower dose of SP increased GnRH concentration later, only in the
      2nd portal blood sample after intracarotid SP injection (p < 0.001). Injection of
      normal saline had no effect on GnRH concentration in pituitary portal blood in
      INT rats. In ORCX, ORCX testosterone- and estrogen-implanted rats portal plasma
      GnRH concentrations were not changed significantly after injection of both doses
      of SP. These results indicate that SP stimulates GnRH release into pituitary
      portal blood and the influence of SP on GnRH neurons depends on the levels of
      circulating gonadal steroid hormones.

PMID- 9588692
TI  - Effect of estrogen on hypothalamic transforming growth factor alpha and
      gonadotropin-releasing hormone gene expression in the female rhesus monkey.
AB  - In order to study whether hypothalamic transforming growth factor alpha
      (TGFalpha) gene expression in the monkey is estrogen-sensitive, long-term
      ovariectomized rhesus macaques were implanted subcutaneously with either
      estradiol-containing (n = 3) or blank (n = 3) Silastic capsules. Blood samples
      were collected every other day while the animals were lightly sedated with
      ketamine hydrochloride to monitor circulating LH and estradiol concentrations.
      Animals were killed with a lethal dose of pentobarbital sodium after a marked
      suppression of LH secretion was confirmed (81 days of estradiol treatment); the
      preoptic area (POA), mediobasal hypothalamus (MBH) and samples of cerebral cortex
      were dissected out, snap-frozen in liquid nitrogen and processed for the
      determination of TGFalpha messenger RNA (mRNA) by ribonuclease protection assay
      using a cRNA probe. The opportunity was also taken to study the action of
      estrogen on hypothalamic GnRH mRNA levels. Although circulating estradiol
      concentrations of 50-150 pg/ml achieved in the steroid-treated group produced a
      decrease in hypothalamic GnRH mRNA levels, which was significant in the MBH,
      TGFalpha mRNA levels in this hypothalamic region and in the POA were not
      influenced by estrogen treatment. These findings indicate that TGFalpha is
      probably not involved in mediating the inhibitory action of estradiol on GnRH
      neurons. Additionally, the relevance of our results to the understanding of the
      neurobiological mechanisms underlying the initiation of puberty in primates is
      discussed.

PMID- 9588693
TI  - Absence of an inhibitory vasopressinergic tone on LH release in pubertal male
      rhesus macaques.
AB  - During puberty, primates begin to secrete LH, and presumably GnRH, at night and
      then eventually throughout the day as they mature. We examined the role of
      vasopressin, a putative inhibitor of the GnRH pulse generator, on LH secretion in
      pubertal male macaques both during the day when the GnRH pulse generator was not
      active and during the night when pulsatile LH secretion was observed. As has been
      found in other primates, LH and testosterone levels were low during the day and
      elevated at night. A potent vasopressin receptor antagonist (VPa) was
      administered during the middle 5 h of a 15-hour daytime or nighttime blood
      collection period to determine the effects on LH, testosterone and cortisol
      secretion. Both during the day and night, cortisol secretion was elevated during
      VPa infusion, suggesting that this V1a receptor antagonist has agonist activity
      on the V1b receptor in the pituitary involved in vasopressin-stimulated
      corticotropin release. Mean LH levels during VPa infusion were not different from
      the control period for that group during the day when LH secretion was absent.
      Mean LH levels were significantly higher (p < 0.05) than pre-VPa LH levels at
      night when pulsatile LH secretion was observed. However, LH levels at night
      during VPa were not higher than levels in untreated animals at the same time. The
      results of these studies demonstrate that LH and testosterone profiles are
      similar to those observed in human males during the pubertal transition and
      suggest that the absence of daytime gonadotropin release during puberty is not
      due to inhibitory vasopressinergic tone on the GnRH pulse generator.

PMID- 9588694
TI  - Components of the neuronal exocytotic machinery in the anterior pituitary of the
      ovariectomised ewe and the effects of oestrogen in gonadotropes as studied with
      confocal microscopy.
AB  - We have investigated exocytotic proteins in ovine pituitary cells and sought to
      identify changes in expression of these proteins related to the effects of
      estrogen on luteinising hormone (LH) secretion in the ovariectomised ewe. Sheep
      were treated with either oestradiol benzoate, or oil (i.m.) and blood samples
      collected for LH assay. Pituitaries were perfusion-fixed and dual-label
      immunohistochemistry was performed to identify hormone-secreting cells, and
      colocalise synaptic proteins within different cell types. Synaptophysin, SNAP-25,
      VAMP-2, rab3A, Munc-18-1, alpha/beta-SNAP, csp, and secretogranin II were
      detected in gonadotropes and somatotropes. Lactotropes were positive for SNAP-25
      and synaptophysin (other synaptic proteins not investigated). Synaptotagmin I was
      detected in gonadotropes and lactotropes, but not somatotropes. Synaptophysin,
      SNAP-25, synaptotagmins I, II and III, VAMP-2, rab3A, Munc-18-1, alpha/beta-SNAP,
      csp, and secretogranin II were detected in nerve fibres of the posterior lobe.
      Membrane staining for SNAP-25 and weak cytoplasmic labelling for both
      synaptotagmin I and secretogranin II were detected in the intermediate lobe.
      Syntaxin and complexin II antibodies did not label any region of the ovine
      pituitary. Oestrogen treatment, to induce a pre-ovulatory-like LH surge, caused
      migration of LH-containing secretory granules toward the plasma membrane of
      gonadotropes, but did not alter the percentage of gonadotropes expressing each
      exocytotic protein. Oestrogen treatment caused a similar redistribution of csp
      and secretogranin II staining in gonadotropes. We conclude that synaptic protein
      expression is not altered in the anterior pituitary at the time when LH secretion
      is maximal. The ubiquitous distribution of many exocytotic proteins suggests that
      all hormone-secreting cells of the pituitary gland contain the same, or similar
      exocytotic machinery, but distinct 'activating factors' are required to
      selectively trigger the secretion of individual hormones.

PMID- 9588695
TI  - Effects of ovariectomy on cerebral flow of rats.
AB  - Recent reports suggest that estrogens may enhance cognitive function in
      postmenopausal women and women suffering from dementia of the Alzheimer's type.
      One of several proposed mechanisms of action of estrogen has been an improvement
      in cerebral blood flow (CBF). The current study examined the effects of estrogen
      deprivation resulting from ovariectomy on the CBF of rats using the quantitative
      autoradiographic 14C-iodoantipyrine technique. CBF was assessed in passively
      restrained, awake adult rats at 6 weeks following ovariectomy (n = 10) or sham
      surgery (n = 10). Rats demonstrated marked endometrial atrophy and a decrease in
      uterine weight (mean 78%) in response to ovariectomy. Ovariectomized animals did
      not differ from control animals both in the magnitude and the topography of
      cortical or subcortical CBF, including the medial preoptic area, amygdala,
      arcuate nucleus and anterior hypothalamus, areas previously associated with high
      estrogen binding. These results suggest that in young, surgically ovariectomized
      animals, hormonal factors do not significantly contribute to changes in basal
      CBF.

PMID- 9588696
TI  - Acute estradiol and progesterone administration reduced cardiovascular and
      catecholamine responses to mental stress in menopausal women.
AB  - Steroid hormones are involved in the regulation of sympathoadrenal activity.
      Since the effect of sex steroids on the cardiovascular system and catecholamine
      secretion could also be exerted through an acute, nongenomic mechanism, we have
      studied the response to mental stress (color word test, CWT) in a group of 15
      menopausal women during estrogen (100 microg of estradiol by patch), progesterone
      (100 mg i.m.) or placebo administration. Systolic blood pressure (SBP) increased
      during CWT in the three sessions (F = 11.0, p < 0.001) but the area under the
      curve of SBP was higher during placebo (2,855 +/- 131 mm Hg x min) than during
      estradiol (2,585 +/- 139 mm Hg x min) and progesterone (2,553 +/- 179 mm Hg x
      min, p < 0.05 for both). Plasma epinephrine increased during CWT in the three
      sessions (F = 31.1, p < 0.001) and the plasma epinephrine response to mental
      stress was higher during placebo than during estradiol administration (F = 4.3, p
      < 0.01). The area under the curve of epinephrine was 10,342 +/- 1,348 pmol/min x
      1 during placebo and 7,280 +/- 818 pmol/min x 1 during estradiol (p < 0.03). The
      plasma glycerol levels at the end of CWT were higher during placebo (0.26 +/-
      0.04 nmol/l) than during estradiol (0.19 +/- 0.03 mmol/l) and progesterone (0.17
      +/- 0.04 mmol/l) administration (p < 0.05 for both). No significant differences
      were found in the responses of diastolic blood pressure, heart rate,
      norepinephrine and cortisol to mental stress during placebo and estradiol or
      progesterone administration. This study demonstrates that acute steroid
      administration is able to modify the cardiovascular and catecholamine response to
      mental stress in menopausal women.

PMID- 9588697
TI  - Effect of bacterial endotoxin on in vivo pulsatile gonadotropin secretion in
      adult male rats.
AB  - Immune system disorders are often accompanied by alterations in the reproductive
      axis. The bacterial endotoxin (lipopolysaccharide or LPS) has central
      inflammatory effects, and activates cytokine release (immune system mediatory
      factors) in the hypothalamus, where the luteinizing hormone-releasing hormone
      neurons are located. The present study was designed to investigate the effect of
      LPS on the pulsatile release of LH and FSH in adult male rats. With this aim,
      orchidectomized male rats were implanted with an atrial catheter and received,
      after two basal blood collections, LPS (250 microg/kg i.v.) or saline.
      Subsequently, blood samples were taken at regular intervals during 110 min. As
      expected, LH release was markedly reduced following exposure to LPS. In order to
      quantify these effects objectively, we subjected these data to PC-pulsar
      analysis. Pulsatile LH release was clearly disrupted in LPS-treated animals as
      compared to control rats: pulse frequency 1.3 +/- 0.3 versus 0.43 +/- 0.2/110
      min, p < 0.05; pulse amplitude 17.18 +/- 2.2 versus 8.33 +/- 0.66 ng/ml, p <
      0.05; overall mean release 15.2 +/- 0.75 versus 7.08 +/- 1.11 ng/ml, p < 0.001;
      maximum values 27.5 +/- 3.08 versus 9.95 +/- 2.16 ng/ml, p < 0.001; baseline
      levels 13.83 +/- 0.77 versus 6.55 +/- 0.74 ng/ml, p < 0.001. Regarding FSH
      secretion, LPS administration significantly lowered baseline levels (p < 0.05)
      and overall mean release (p < 0.01); FSH pulsatility parameters showed no
      significant differences. These observations indicate that LPS decreases LH and
      FSH mean release rates and baseline levels and inhibits several pulsatility
      parameters of LH release (frequency, amplitude and maximum values); FSH
      pulsatility parameters are not altered by LPS administration. We speculate that
      this effect is exerted principally at the hypothalamic level by modifying GnRH
      secretion.

PMID- 9588698
TI  - Neurohypophysial peptides stimulate the phosphorylation of pre-T cell focal
      adhesion kinases.
AB  - Thymic oxytocin (OT) behaves as a cryptocrine signal targeted at the outer
      surface of thymic epithelial cell plasma membrane from where OT is able to
      interact with neurohypophysial peptide receptors expressed by pre-T cells.
      Immature T cells bear a receptor of the V1 subtype, while OT receptors are
      predominantly expressed by cytotoxic CD8+ lymphocytes. In both T cell types,
      neurohypophysial peptide receptors transduce OT via the phosphoinositide pathway.
      Protein tyrosine phosphorylation is an early event of T cell activation. Western
      blots of murine pre-T cells (RL12-NP line) proteins probed with anti
      phosphotyrosine (PY-20) revealed a great number of proteins the phosphorylation
      of which increased either with OT or vasopressin treatment. Two were
      immunoprecipitated with anti-focal adhesion kinase (FAK) mAb 2A7 and were
      identified one as p125FAK and the other as a coprecipitating 130-kDa protein. The
      p125FAK is connected to the Ras/MAPK pathway and is also implicated in TCR/CD3
      signalling in T cell. Another protein phosphorylated by OT in RL12-NP was
      identified as paxillin, a 68-kDa protein localised at focal adhesion sites and
      associated with p 125FAK. These results indicate that phosphorylation of focal
      adhesion kinase may be induced in pre-T cell by thymic OT.

PMID- 9588699
TI  - New combined treatment of surgery, radiotherapy, and reconstruction in head and
      neck rhabdomyosarcoma in children: the AMORE protocol.
AB  - BACKGROUND: If no complete remission on chemotherapy is reached in head and neck
      rhabdomyosarcoma (RMS) in children, adjuvant radiotherapy and/or surgery are
      indicated. This often causes severe mutilation, and the prognosis is poor.
      Ablative surgery, moulage technique with afterloading brachytherapy, and
      reconstructive surgery, called the AMORE protocol, is developed for residual or
      recurrent disease after chemotherapy. METHODS: Ablative surgery with preservation
      of important structures is followed by the embedding of a gutta-percha mold in
      the created tissue defect. The wound bed is irradiated with Iridium192. Within 1
      week, the defect is reconstructed with a muscle transplant. Fifteen children
      (mean age, 5.7 years) were treated accordingly. RESULTS: All patients were
      discharged within 4 weeks. Eleven patients are tumor-free, with a mean follow-up
      period of 2.8 years. No signs of radiation sequelae were observed. CONCLUSION:
      The preliminary results of this new, combined treatment are encouraging, if the
      advanced stage of disease is considered.

PMID- 9588700
TI  - Surgery of thyroid cancer in children and adolescents.
AB  - BACKGROUND: Thyroid carcinoma in young patients under the age of 20 years is
      uncommon. Because of the slow progression of this disease, there is still a great
      deal of debate as to which operation strategy is best. METHODS: We undertook a
      retrospective study of 61 patients under 20 years of age with thyroid cancer
      treated at our institute between 1952 and 1995. They constitute 6.6% of the 921
      thyroid cancer patients treated by us during the same period. Factors examined
      were: symptoms, metastases, treatment, complications, and survival. RESULTS:
      Total or near-total thyroidectomy was performed in 51 patients. Regional lymph
      node dissection was performed in 17 patients and modified radical neck dissection
      in 13. Fifty-one patients underwent pretracheal and paratracheal lymph node
      dissection. During the 43 years of this study, two patients died of thyroid
      cancer. CONCLUSIONS: Although most children are initially seen with more
      extensive disease than adults, the overall prognosis is excellent. The excellent
      prognosis is the product of initial aggressive treatment: near-total or total
      thyroidectomy and at least pre- and paratracheal lymph node dissection, followed
      by radioactive iodine therapy.

PMID- 9588701
TI  - Sublethal damage repair capacity in carcinoma cell lines with p53 mutations.
AB  - BACKGROUND: The previous findings that sublethal damage repair (SLDR) capacity
      varies between carcinoma cell lines and that the inherent radiosensitivity of
      these lines tends to be higher in connection with p53 mutations lead us to study
      the possible role of p53 gene in the regulation of SLDR. The activation of p53
      gene by irradiation is known to cause changes in cell cycle progression. Thus,
      p53 status probably has effects on cellular radiosensitivity, theoretically
      through modulating repair processes. METHODS: The SDLR capacity of 17 head and
      neck carcinoma cell lines was determined in split-dose experiments using a 96
      well plate clonogenic assay. The SLDR capacity as well as the inherent
      radiosensitivity were compared with the p53 status of the cells. RESULTS: The
      SLDR capacity varied markedly also between cell lines of similar
      radiosensitivity, but there was a tendency of the more sensitive cells to be more
      SLDR proficient .(r = -.69; p = .0016). The (beta-values obtained from linear
      quadratic equation correlated well with the observed amount of SLDR (r = .73; p =
      .0006). With one exception, those cell lines having p53 mutations showed higher
      SLDR than those with no mutations (p = .0017). In many of these cell lines, the
      mutations caused either total loss of the p53 protein or major, probably
      functional changes in it. The cell line UT-SCC-16A, showing no SLDR in the
      experiments, had two mutation points in different alleles, perhaps having less
      effect on the protein function. CONCLUSION: This extended material confirmed the
      previous result that the SLDR capacity tends to increase with increasing
      radiosensitivity in carcinoma cell lines. A clear correlation between p53
      mutations and SLDR capacity was found. The SLDR depended, however, on loss of
      normal p53 function, which implies that the p53-mediated G1 arrest is not as
      important in this repair process, as would have been expected.

PMID- 9588702
TI  - Endothelial constitutive nitric oxide synthase (ecNOS) localization in normal and
      neoplastic salivary tissue.
AB  - BACKGROUND: Nitric oxide (NO.) has been implicated in the process of
      carcinogenesis in various organs. This study was designed to investigate the
      expression of endothelial constitutive nitric oxide synthase (ecNOS) in normal
      and neoplastic salivary tissues. METHODS: Paraffin-embedded tissue from 48
      salivary tumors and adjacent non-neoplastic tissue was immunohistochemically
      evaluated for both frequency (percentage) and intensity (1-4+) of staining using
      a commercially available anti-ecNOS monoclonal antibody. RESULTS: Expression of
      ecNOS was predominantly localized to vascular endothelium, skeletal muscle, and
      to salivary duct luminal epithelium in normal salivary tissue (n = 37). All
      salivary tumors demonstrated at least 1 + cytoplasmic staining for ecNOS without
      apparent correlation to most clinical parameters. A tendency toward increased
      frequency and intensity of ecNOS expression in oncocytic cells, relative to cells
      with myoepithelial or acinar differentiation, was noted. CONCLUSIONS: Expression
      of ecNOS is localized to the luminal cells of normal salivary ducts. Limited
      expression of ecNOS was found in all the salivary gland tumors examined. This
      suggests a common histogenesis for this diverse group of tumors, which may
      reflect different degrees of differentiation toward luminal duct epithelium. The
      possible role of ecNOS and NO. in salivary gland carcinogenesis is intriguing and
      warrants further study.

PMID- 9588703
TI  - Sensate osteocutaneous fibula flap: anatomic study of the innervation pattern of
      the skin flap.
AB  - BACKGROUND: For oromandibular reconstructions, an osteocutaneous fibula flap
      provides sufficient bone and pliable skin. Sensory reinnervation could possibly
      prevent problems in mastication and deglutition. METHODS: In this anatomic study,
      33 cadaver limbs were microsurgical dissected. We investigated the lateral sural
      cutaneous nerve (LSCN), which supplies sensation to the skin of the lateral lower
      leg, in relation to the fibula skin flap. The fibula is vascularized by the
      peroneal vessels via the posterior intermuscular septum. Therefore, the posterior
      septum determines the center line of the flap design. RESULTS: The LSCN runs in
      74% of the dissections posterior to the posterior septum, whereas an anterior
      branch was seen in 26%. In 54% of the dissections, the distance to the posterior
      septum was within 3 cm from the septum, whereas in 86%, the distance was found to
      be within 4 cm. CONCLUSION: The skin flap should be designed more posteriorly to
      achieve maximal reinnervation.

PMID- 9588704
TI  - Obliteration of the frontal sinus cavity with bioactive glass.
AB  - BACKGROUND: Bioactive glass (BG) is a glass ceramic material. It has been used as
      surgical bone replacement material in ear and oral surgery, orthopedics, and
      dentistry. METHODS: Bioactive glass was used as obliteration material in a series
      of osteoplastic frontal sinus operations on 10 patients suffering from chronic
      frontal sinusitis, which other, more-conservative treatment modalities had failed
      to cure. RESULTS: Bioactive glass is easy to handle, and complete obliteration of
      all sinusal recesses and excavations is easily achieved. No adverse effects of
      the implant material have been seen over a mean follow-up period of 5.0 years.
      One patient with a local recurrent infection in the outer table of the sinus was
      reoperated on 5 months after primary surgery. Repeated postoperative computed
      tomographic scans analyzed by digital region-of-interest (ROI) selection showed
      no remarkable changes in the frontal sinus cavities but a slight, yearly decrease
      in the density of the occlusion material. Laboratory monitoring of patients and
      histopathologic examination of two postoperative biopsy specimens indicated that
      the material is well tolerated and stable. CONCLUSIONS: Bioactive glass is a
      promising and well-tolerated bone graft suitable for osteoplastic frontal sinus
      operations. Total accurate obliteration of the sinus is achieved with different
      sizes of granules and blocks. The results of the obliteration are maintained
      owing to the stability of the material.

PMID- 9588705
TI  - Differential expression of epidermal growth factor receptor in human head and
      neck cancers.
AB  - BACKGROUND: Over-expression of human epidermal growth factor receptor (EGFR) is
      associated with a variety of human malignancies, including head and neck cancer.
      It has also been studied for its effect on cancer cell responses to chemotherapy.
      To accurately measure changes in EGFR expression that might be of diagnostic or
      prognostic importance in head and neck cancers, a quantitative assay for the
      direct detection of EGFR messenger ribonucleic acid (mRNA) was developed.
      METHODS: Our method was based on competitive reverse transcriptase-polymerase
      chain reaction (RT-PCR) that was able to measure EGFR mRNA levels undetectable by
      northern-blot analysis. We measured EGFR mRNA by RT-PCR in human head and neck
      cancers and their corresponding adjacent, histologically normal tissues and in
      cisplatin-treated and untreated oral epithelial cell lines. RESULTS: All the
      tumor samples had higher EGFR mRNA levels than their corresponding adjacent
      normal tissues. It is also shown that EGFR mRNA levels in normal oral epithelial
      cells were elevated after exposure to cisplatin. In contrast, EGFR mRNA levels in
      oral cancer cells were decreased after the exposure, suggesting that increased
      EGFR expression may have different functions in cancer cells and in normal cells
      under stress. CONCLUSIONS: Accurate monitoring of EGFR expression may be a useful
      marker for diagnosis, treatment, and prognosis of head and neck cancer.

PMID- 9588706
TI  - Delayed regional metastasis from midfacial squamous carcinomas.
AB  - BACKGROUND: Metastases from mucosal and cutaneous carcinomas can present in a
      delayed fashion, and this late presentation may confer a different prognosis
      after conventional treatment. METHODS: We present a series of patients in which
      there was a significant time delay between the treatment of a squamous carcinoma
      of the skin or mucosa of the midface and the detection of regional metastases in
      12 of the 13 cases. Primary tumors were located on the lower lip and commissure
      (n = 3), nasal tip (n = 2), nasal ala (n = 1), columella (n = 1), nasofacial
      crease (n = 2), maxillary alveolus (n = 3), and mandibular alveolus (n = 1).
      Metastatic spread manifested by palpable perifacial or submandibular lymph nodes
      was not evident until greater than 11 months after the treatment of the primary
      site in 12 of 13 patients (range, 3-45 months). Nine of the patients were
      clinically staged as N1, whereas there was one each in the N2a, N2b, N2c, and N3
      categories. Eleven of the 13 patients were initially seen with palpable disease
      involving the perifacial nodes within or around the submandibular gland. All
      patients were treated with neck dissection except one, who refused surgical
      treatment and underwent a second course of radiotherapy to the cervical region.
      The nine patients initially seen with clinical stage N1 disease underwent neck
      dissection with preservation of the sternocleidomastoid, internal jugular vein,
      and accessory nerve. RESULTS: Of 10 patients with perifacial node metastases who
      underwent neck dissection, 8 required sacrifice of the marginal mandibular nerve
      and overlying platysma to gain adequate margin. Extracapsular spread was present
      in 11 patients, (8 of 9 who were clinically N1). Postoperative radiotherapy was
      recommended to all patients with extracapsular spread, although only 7 of the 11
      received radiotherapy. There were no regional recurrences after a minimum follow
      up of 1 year (range, 12-65 months; mean, 31.4 months). Histologic grade appeared
      to have no influence on prognosis. CONCLUSIONS: This cohort demonstrates the
      ability of midfacial squamous cell carcinoma to manifest regional metastatic
      disease over a delayed time. This delayed presentation appears to confer a more
      favorable response to treatment. For midfacial cancers, the perifacial nodes are
      at greatest risk for metastatic spread. For tumors in this region, primary
      treatment of the neck is probably not warranted, but careful extended follow-up
      for the potential of delayed cervical metastasis is prudent.

PMID- 9588707
TI  - Arachidonic acid metabolism: a primer for head and neck surgeons.
AB  - The arachidonic acid metabolites, or eicosanoids, are a large series of lipid
      derived mediators capable of producing a multitude of physiologic effects in the
      local environment. They play important roles in a variety of signaling pathways
      in endocrinology, immunology, and oncology. A significant body of work in this
      area has occurred in squamous cell carcinomas of the head and neck over the past
      15 years. This review will attempt to familiarize the head and neck surgical
      oncologist with the basic biochemical steps in the formation of these compounds,
      newer developments in the field of eicosanoid biochemistry, and related
      experimental evidence of the roles of these substances in head and neck cancer.

PMID- 9588708
TI  - Spontaneous cervical hemorrhage with near-complete airway obstruction.
AB  - BACKGROUND: Retropharyngeal hematoma is a rare entity which may progress rapidly
      to airway obstruction. Previously documented causes have included coagulopathic
      states, trauma, infection, parathyroid adenoma rupture, and foreign-object
      ingestion. Four cases of spontaneous retropharyngeal hematomas without any known
      predisposing risk factors have been previously reported. Two of these cases had
      fatal outcomes. METHODS: A case report is presented and the literature reviewed.
      RESULTS: Spontaneous cervical hematoma with parapharyngeal and retropharyngeal
      involvement which caused near-complete respiratory obstruction occurred in an
      otherwise healthy young man following straining. Initial management involved
      fiberoptic nasotracheal intubation. Subsequent right neck exploration revealed
      hemorrhage from a branch of the external carotid artery, which was ligated. An
      arteriogram revealed minimal flow through the right external carotid artery and
      its branches. The patient was extubated and discharged uneventfully on the fourth
      postoperative day. CONCLUSION: The possible etiology for this case is discussed,
      and a review of the literature and the role of surgery in the management of this
      entity is outlined.

PMID- 9588709
TI  - Sample size estimations.

PMID- 9588710
TI  - Value of preliminary sample size estimations.

PMID- 9588711
TI  - Microvascular soft-tissue coverage and distraction osteosynthesis for lower
      extremity salvage.
AB  - In our attempts to salvage massive lower-extremity injuries, even in the presence
      of severe peripheral vascular pathology, adequate soft-tissue coverage is no
      longer a limiting factor due to recent advances in microvascular composite tissue
      transfer. Restoration of tibial continuity without shortening has emerged as the
      last obstacle in the formidable task of salvaging lower extremities with grade
      III B and III C defects. Proposed solutions to this problem include conventional
      free cancellous bone-grafting applicable to small defects only, vascularized bone
      grafts, or shortening of the leg with subsequent elongation using the Ilizarov
      technique. We present our experience with 3 consecutive cases of lower-limb
      salvage, utilizing a new approach in which microsurgical soft-tissue
      reconstruction has been combined with bony reconstruction by distraction
      osteosynthesis. Bone transport by distraction osteosynthesis under a free flap
      performed while preserving the initial limb length throughout the treatment
      period proved to be superior to other methods in selected cases and is presented
      as a new technique for the management of problematic lower-limb injuries.

PMID- 9588712
TI  - Structural recovery of small arteries following clamp injury: a light and
      electron microscopic investigation in the rat.
AB  - Endothelial injuries were induced in the left common iliac arteries (1 mm in
      diameter) of rats, by the placement of 1 mm Scovell-Lewis microvascular clamps
      for 5 minutes, to create a lesion in which to quantitate the rate and degree of
      cellular regeneration. The left (clamp-injured) and right (control) iliac
      arteries from the 15 rats used in this study were viewed with the electron
      microscope at 2, 7, and 14 days after clamping, and the clamp sites were analysed
      morphometrically. At 2 days there was only minimal denudation of the endothelium;
      most cells were disoriented and showed some signs of traumatic injury. By 7 days
      there was a completely continuous endothelial lining, but there was also evidence
      of increased cytoplasmic activity in these cells, as well as a statistically
      significant simplification in their intercellular junctional morphology. These
      changes persisted at 14 days after injury, but they were less pronounced. Smooth
      muscle cells in the media were relatively unaffected by the trauma in the first 2
      days after clamping. However, they exhibited a change of phenotype from
      contractile to synthetic by 7 days after injury. By 14 days most smooth muscle
      cells had reverted back to the contractile phenotype, with little evidence of
      residual damage. These studies reveal that the reconstitution and regeneration of
      the endothelium is very rapid following clamp injury, but that significant
      residual ultrastructural changes in the interendothelial junctions persist for at
      least 14 days after injury. These findings indicate that there is potential for
      subsequent pathological changes in sites of vascular clamp injury.

PMID- 9588713
TI  - Construction of a vein-pouch aneurysm at a surgically created carotid bifurcation
      in the rat.
AB  - Currently available animal models for the study of treatment of aneurysms are
      either expensive or yield unreliable results. An animal series was devised to
      address both of these problems by creating a new animal model. Twelve Sprague
      Dawley rats were used to demonstrate that a vein-pouch aneurysm could be
      constructed at a surgically created carotid bifurcation. Patency rates, growth
      dynamics, and histologic morphology were studied at three time intervals. A 100%
      patency rate at the aneurysm orifice was achieved with one-third of the aneurysms
      showing varying degrees of partial apical thrombosis. A growth pattern was
      established over the study period. Magnetic resonance angiography and digital
      subtraction angiography were successfully employed to study a small number of
      additional aneurysms. Our conclusion is that a bifurcation aneurysm can be
      constructed in the rat with high patency rates and predictable saccular
      morphology which resembles most human intracranial aneurysms. This inexpensive
      animal model can be used to study novel modalities for the treatment of
      aneurysms.

PMID- 9588714
TI  - Detailed modified technique for safer harvesting and preparation of liver graft
      in the rat.
AB  - Liver procurement and preparation for orthotopic liver transplantation (OLT) in
      the rat is the first stage for beginners aiming to acquire mastery of this model.
      It requires extensive and precise dissection in which each detail must provide
      security for the procurement and perfection for the future graft. Many technical
      details, "tricks and secrets," remain known only by expert teams, so that the
      learning phase can be long or unsuccessful if a period in such a team is not
      possible. We describe this procedure in great detail, including many improvements
      to the original technique. Complete illustration is provided to enable an easier
      appreciation of what remains the critical first part of the most difficult
      transplant model to perform in the rat.

PMID- 9588716
TI  - Arteriovenous malformation of the base of tongue: case report and literature
      review.
AB  - Arteriovenous malformations of the head and neck pose a challenging therapeutic
      and reconstructive problem. In this report we describe a rare case of an
      arteriovenous malformation of the base of tongue. The patient, a young adult
      female, was treated with embolization followed by surgical resection using a
      lateral pharyngotomy approach. Reconstruction of the extensive base of tongue
      defect was accomplished using a radial forearm free flap. Currently, the patient
      is decannulated, articulates clearly, tolerates a normal diet, and is without
      recurrence. Our treatment approach is discussed in detail and compared with
      alternative techniques.

PMID- 9588715
TI  - Cyclosporine A inhibits lymphocyte migration into ovine peripheral nerve
      allografts.
AB  - Lymphocyte migration into nerve allografts was measured to estimate the
      cyclosporine A (CsA) dose required to suppress rejection. Twelve outbred sheep
      received daily subcutaneous CsA at 0, 5, 10, or 15 mg/kg/day for 2 weeks prior to
      implantation of multiple heterotopic subcutaneous nerve grafts. Lymphocyte
      migration was determined after 7 days by an intravenous pulse of autologous
      111indium-labeled lymphocytes and subsequent quantitation of gamma radioactivity
      in nerve tissue (CPM/g, mean +/- SEM). Measurement by radioimmunoassay revealed a
      dose-dependent increase in blood cyclosporine levels. Lymphocyte migration into
      autografts (404+/-44) was significantly less than migration into allografts
      (16,554+/-2,049), in control animals (P < 0.01). A dose-dependent inhibition of
      lymphocyte migration into nerve allografts was observed with counts of 7,662+/
      1,692, 4,083+/-1,112, and 1,561+/-232 in sheep receiving 5, 10, or 15 mg/kg/day
      of CsA, respectively. Daily CsA administration produced effective blood levels
      and immunosuppression sufficient to inhibit lymphocyte migration into nerve
      allografts.

PMID- 9588717
TI  - Experimental prevention of free flap thrombosis. I: A model of free flap failure.
AB  - A model to evaluate the efficacy of therapies aimed at reducing the failure rate
      of microvascular free flaps was developed in the rat, inspired by earlier work on
      the rabbit ear by Ozbek et al. (Ann Plast Surg 32:474-477, 1994). It consisted in
      raising an epigastric groin flap on the femoral pedicle, while cutting the
      femoral artery, twisting it around the femoral vein, and resuturing it. Immediate
      patency was always seen, but 19 of 20 such anastomoses presented with thrombosis
      after 24 hours (15 venous and 4 mixed thromboses). Ten similar anastomoses
      performed without twisting did not result in thrombosis (P = 0.000000366). This
      model appears to be adequate for simulating free flap failure.

PMID- 9588718
TI  - Experimental prevention of free flap thrombosis. II: Normovolemic hemodilution
      for thrombosis prevention.
AB  - A microvascular free flap failure model consisting of raising an epigastric groin
      flap on the femoral pedicle, while cutting the femoral artery, twisting it around
      the femoral vein and resuturing it, has been previously described. As it was
      being evaluated, normovolemic hemodilution as a means to prevent thrombosis was
      simultaneously assessed using an additional experimental group. Twenty percent of
      the blood mass of each rat was taken and replaced with a hydroxyethyl starch
      solution immediately before surgery. Only 14 out of 20 anastomoses presented with
      thrombosis (13 venous and one mixed), as opposed to 19 out of 20 animals operated
      on without hemodilution (P< 0.05). Normovolemic hemodilution appears to be an
      effective method of reducing microvascular free flap failure.

PMID- 9588719
TI  - Margin of resection in the management of primary melanoma.
AB  - In the last 20 years, it has become evident that the continued use of 4 to 5 cm
      margins of resection around a primary melanoma is not justified. A prospective
      randomized trial by the World Health Organization (WHO) Melanoma Group showed
      that for melanomas up to 2 mm thick, a 1 cm margin provides local control similar
      to that observed after a 3 cm margin. Another prospective randomized trial by the
      Melanoma Intergroup Committee in the United States concluded that for melanomas 1
      to 4 mm in thickness, a 2 cm margin of resection provides local control that is
      as good as a 4 cm margin. For melanomas thicker than 4 mm, the current evidence
      suggests that a 2 cm margin is adequate, the chief manifestation of recurrence
      for these thick lesions being hematogenous and lymphogenous spread. The adoption
      of the narrower surgical margins suggested above should reduce the morbidity
      caused by the radical margins of the past without compromising local control of
      the disease.

PMID- 9588720
TI  - Role of elective lymph node dissection in melanoma.
AB  - In the last several years, much debate has centered on the management of the
      regional lymph nodes in malignant melanoma. The regional lymph nodes are the most
      common site of melanoma metastases and surgical excision of these involved nodes
      is the most effective treatment for either cure or local disease control. The
      issue still in question is the approach to the clinically negative regional lymph
      node basin. Retrospective studies have yielded conflicting results regarding the
      value of routine elective lymph node dissection (ELND) when nodes are clinically
      negative. Four prospective randomized clinical trials have been completed which
      have indicated that routine ELND is not worthwhile for the majority of melanoma
      patients. However, ELND may be associated with improved outcome in certain
      subgroups of patients: those <60 years age with 1 to 2 mm thick melanomas with or
      without ulceration. In addition, lymphatic mapping with sentinel lymph node
      biopsy has become increasingly available and has allowed clinicians an
      alternative to ELND. In the absence of sentinel lymph node biopsy, the role for
      ELND in these subgroups of patients is one of the remaining unresolved issues.

PMID- 9588721
TI  - Lymphatic mapping and sentinel lymphadenectomy for melanoma.
AB  - Intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) for patients
      with clinical Stage I melanoma was developed to determine the tumor status of the
      regional lymphatic basin without elective regional node dissection. Only
      individuals with histologically confirmed sentinel node (SN) metastases undergo
      complete regional node dissection, sparing those with tumor-free SN the morbidity
      of this procedure. Studies worldwide have confirmed the validity of the SN
      concept and the accuracy of SLND as a staging procedure. The incidence of false
      negative SN and the rate of recurrence in the regional node basin have been low.
      Routine preoperative lymphoscintigraphy and refinements in surgical technique
      have improved the accuracy of SLND for melanoma, making it the nodal staging
      procedure of choice when undertaken by an experienced nuclear medicine physician,
      surgical oncologist and pathologist. Ongoing studies are investigating the impact
      of SLND on survival as well as the prognostic significance of micrometastasis
      detected by histopathologic and molecular techniques.

PMID- 9588722
TI  - Therapeutic node dissections in malignant melanoma.
AB  - In the absence of distant disease, therapeutic node dissections in malignant
      melanoma, i.e., dissections of regional nodal basins for palpable suspicious or
      biopsy-proven positive nodes, offer the chance of cure. The 5-year survival rates
      after therapeutic lymphadenectomy closely correlate with expected cure rates.
      Although they varied greatly in the literature, from 19% to 38%, the currently
      obtainable survival rates are in the upper ranges of this spectrum because
      patients now are closely followed-up and operated for early palpable nodal
      disease. Properly done, these procedures carry a low morbidity, but they should
      be done thoroughly to completely eradicate regional disease and avoid recurrences
      in the same nodal basin to achieve the maximum survival that is surgically
      attainable.

PMID- 9588723
TI  - Adjuvant therapy of melanoma.
AB  - Patients with AJCC Stage IIB and III melanoma have a poor 5-year survival rate
      which has been the driving force behind attempts to find an effective adjuvant
      therapy for this stage of disease that would effectively reduce relapse and
      improve survival. Immunotherapy with bacillus Calmette-Guerin (BCG),
      Corynebacterium parvum, and levamisole have not been successful in achieving this
      goal, nor have trials with chemotherapy in the adjuvant setting, including high
      dose chemotherapy with autologous bone marrow transplantation. The recent Eastern
      Cooperative Oncology Group (ECOG) 1684 study showed significant improvement in
      relapse-free and overall survival with high doses of alpha interferon (IFNalpha)
      given for 1 year. Lower dosages of IFNalpha have to date been unsuccessful in
      impacting upon long-term survival. Recent data with vaccines have been
      encouraging, and the GM2-KLH vaccine is the focus of ongoing intergroup study
      comparing this treatment with IFNalpha in resected Stage IIB and III melanoma.
      The various regimens are reviewed in this article.

PMID- 9588724
TI  - Surgery for metastatic melanoma.
AB  - The appearance of distant metastases in a patient with malignant melanoma usually
      prophesies an early death: median survival is only 5 to 8 months. Surgery
      definitely can palliate certain patients and lead to a prolongation of life for
      others. In selected surgical candidates, an isolated nonvisceral metastasis,
      complete resection with free surgical margins, and a longer disease-free interval
      all favorably affect prognosis. In such cases, median survival can even approach
      10 years, with a 5-year survival of up to 35%. Lung metastases are often
      incidental findings, but if complete resection can be accomplished, sometimes a
      median survival of 19 months and a 5-year 25% survival can be seen. Patients
      rarely survive long-term after brain or gastrointestinal metastases present
      themselves, but surgical resection extends median survival to about 10 months in
      this group with a significant improvement in quality of life. General guidelines
      should be reasonably applied for surgical intervention, with each metastatic
      melanoma patient given special individual assessment. Little has changed since
      the topic of the surgical role in metastatic melanoma was last reviewed in this
      journal by Coit in 1993.

PMID- 9588725
TI  - Systemic therapy in melanoma.
AB  - The patient with surgically incurable melanoma presents a difficult problem for
      the medical oncologist. Single chemotherapeutic agents at conventional doses
      produce bona fide but infrequent remissions. The most active single agent for the
      treatment of metastatic melanoma is dacarbazine (DTIC). Until recently,
      combinations of drugs yielded no real improvement over treatment with the
      individual components. The combination of DTIC + carmustine (BCNU) + cisplatin +
      tamoxifen (the "Dartmouth regimen") appears to be more effective than DTIC alone,
      but prospective randomized trials comparing the two are still in progress. The
      contribution of tamoxifen to the observed results continues to be evaluated.
      Biological agents, such as interferon and interleukin-2, have lower overall
      response rates compared to chemotherapy regimens, but response duration appears
      to be longer. Chemotherapy combined with biotherapy offers the promise of higher
      response rates and long-term durable remissions. The results from high-dose
      regimens that use autologous bone marrow or peripheral stem cell support have not
      been sufficient to justify the added toxicity. Although advanced melanoma often
      is not curable with systemic therapy, the considered use of currently available
      regimens can induce clinically significant remissions and, possibly, prolong life
      in some patients.

PMID- 9588726
TI  - Overview of melanoma vaccines: active specific immunotherapy for melanoma
      patients.
AB  - Although a phase III trial has yet to show a statistically significant
      improvement in the disease-free or overall survival of melanoma patients
      receiving vaccine therapy, several phase II trials have shown enhanced disease
      free and overall survival of patients who develop a humoral and/or cellular
      response to a melanoma vaccine. The challenge of active specific immunotherapy
      research is to determine which combination of humoral and cellular immune
      responses optimizes clinical outcome and how to monitor the immune response
      effectively. This review identifies key components of a successful melanoma
      vaccine, discusses new ways to modulate and stimulate the immune system, and
      summarizes some of the important clinical trials of active specific immunotherapy
      for patients with melanoma.

PMID- 9588727
TI  - A new hypothesis of modular glucocorticoid actions: steroid treatment of
      rheumatic diseases revisited.

PMID- 9588728
TI  - Mixed connective tissue disease: to be or not to be?

PMID- 9588729
TI  - Estimates of the prevalence of arthritis and selected musculoskeletal disorders
      in the United States.
AB  - OBJECTIVE: To provide a single source for the best available estimates of the
      national prevalence of arthritis in general and of selected musculoskeletal
      disorders (osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis,
      the spondylarthropathies, systemic lupus erythematosus, scleroderma, polymyalgia
      rheumatica/giant cell arteritis, gout, fibromyalgia, and low back pain). METHODS:
      The National Arthritis Data Workgroup reviewed data from available surveys, such
      as the National Health and Nutrition Examination Survey series. For overall
      national estimates, we used surveys based on representative samples. Because data
      based on national population samples are unavailable for most specific
      musculoskeletal conditions, we derived data from various smaller survey samples
      from defined populations. Prevalence estimates from these surveys were linked to
      1990 US Bureau of the Census population data to calculate national estimates. We
      also estimated the expected frequency of arthritis in the year 2020. RESULTS:
      Current national estimates are provided, with important caveats regarding their
      interpretation, for self-reported arthritis and selected conditions. An estimated
      15% (40 million) of Americans had some form of arthritis in 1995. By the year
      2020, an estimated 18.2% (59.4 million) will be affected. CONCLUSION: Given the
      limitations of the data on which they are based, this report provides the best
      available prevalence estimates for arthritis and other rheumatic conditions
      overall, and for selected musculoskeletal disorders, in the US population.

PMID- 9588730
TI  - Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic
      role for endothelin 1.
AB  - OBJECTIVE: To explore a possible correlation between endothelin 1 (ET-1), the
      most potent endothelium-derived contracting factor that modulates vascular smooth
      muscle tone, and arterial disease in patients with the antiphospholipid syndrome
      (APS). METHODS: Plasma levels of ET-1 were measured in APS patients with (n = 16)
      and without (n = 11) arterial thrombosis and in non-APS patients with arterial
      thrombosis (n = 9). In addition, steady-state prepro-ET-1 messenger RNA (mRNA)
      levels were determined in endothelial cells treated with a range of human
      monoclonal anticardiolipin antibodies (aCL) (as anti-beta2-glycoprotein I
      antibodies) by semiquantitative 32P-dCTP-labeled reverse transcription-polymerase
      chain reaction. RESULTS: Compared with healthy controls, markedly increased
      plasma levels of ET-1 were found in APS patients with arterial thrombosis (2.00
      +/- 0.87 versus 0.96 +/- 0.37 pg/ml; P = 0.0001) but not in other groups. Three
      human monoclonal aCL induced prepro-ET-1 mRNA levels significantly more than did
      control monoclonal antibody lacking aCL activity. CONCLUSION: Plasma ET-1 levels
      correlated significantly with a history of arterial thrombosis in patients with
      APS. Prepro-ET-1 mRNA was induced by human monoclonal aCL in the in vitro
      experimental system. The induction of ET-1 by antiphospholipid antibodies might
      contribute to increased arterial tone, leading to vasospasm and, ultimately, to
      arterial occlusion.

PMID- 9588731
TI  - Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized,
      double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic
      Arthritis Study Group.
AB  - OBJECTIVE: To assess the efficacy, tolerability, and safety of sulfasalazine
      (SSZ) in the treatment of juvenile chronic arthritis (JCA). METHODS: We conducted
      a 24-week randomized, placebo-controlled, double-blind, multicenter study of
      patients with active JCA of both oligoarticular and polyarticular onset. Patients
      were treated with a dosage of 50 mg/kg/day of SSZ (maximum 2,000 mg/day) or
      placebo. The efficacy variables were joint scores, physician's, parents', and
      patient's overall assessments, and laboratory parameters of inflammation.
      RESULTS: Of the 69 patients enrolled, 52 (75%) completed the trial. Six patients
      (18%) withdrew from the placebo group, and 11 (31%) withdrew from the SSZ group
      (P = 0.18). In the intention-to-treat analysis of end point efficacy, between
      group differences were significant for the overall articular severity score (P =
      0.02), all global assessments (P = 0.01), and the laboratory parameters (P <
      0.001). Adverse events occurred more frequently in the SSZ group and were the
      main reason for withdrawal (P < 0.001), but in all instances, these events were
      transient or reversible upon cessation of treatment. CONCLUSION: The results of
      this first placebo-controlled study show that SSZ is effective and safe in the
      treatment of children with oligoarticular- and polyarticular-onset JCA, although
      it was not well tolerated in one-third of the patients.

PMID- 9588732
TI  - The influence of sex on the phenotype of rheumatoid arthritis.
AB  - OBJECTIVE: To explore whether there are different disease patterns of rheumatoid
      arthritis (RA) in women and men. METHODS: We studied 55 male case patients and
      110 female control patients who developed RA between 1970 and 1985 and who
      resided and received medical care in Olmsted County, Minnesota, for at least 10
      years after the diagnosis of RA. Case and control patients were matched for the
      date of first diagnosis. The pattern and extent of joint involvement, the
      frequency of joint surgeries, and the presence and type of extraarticular
      manifestations were determined by retrospective chart review. RESULTS: Incidence
      rates in women were variable and age dependent, whereas the risk in men older
      than 36 years was constant over their lifetime. Erosive disease was more frequent
      in men than in women (72% versus 55%, respectively; P < 0.05) and tended to occur
      earlier (47% versus 31% for erosive disease within the first 4 years of RA).
      Although male sex was correlated with a higher risk of bony erosions and an
      accelerated course of RA, structural consequences of joint destruction were more
      pronounced in women. Joint surgery was performed more frequently in women (50%)
      than in men (27%) (P = 0.01). In particular, the frequencies of arthroplasties
      and arthrodeses of hand and foot joints were different (34 procedures in women
      versus 1 procedure in men; P < 0.001). Sex influenced the risk as well as the
      pattern of organ involvement in RA. Nodules and rheumatoid lung disease were
      typical manifestations in men (P = 0.001 and P < 0.001, respectively), whereas
      women typically developed sicca syndrome (P = 0.05). Despite differences in
      disease aggressiveness and disease pattern, there was little difference in the
      medical therapy in the men compared with the women. CONCLUSION: RA is a
      heterogeneous disease with variations in phenotype. Sex-associated factors
      influence disease severity as well as disease pattern. Because sex-related
      effects influence treatment goals, treatment responses, and side effects, they
      should be considered in clinical study design and analysis as well as in the
      treatment decisions for individual patients with RA.

PMID- 9588733
TI  - Apoptosis of lymphocytes induced by glucocorticoids and relationship to
      therapeutic efficacy in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Glucocorticoids (GCs) are the drugs of first choice for treatment of
      systemic lupus erythematosus (SLE). However, the disease in some patients is
      resistant to these agents. This study evaluated the possibility of a relationship
      between response to GC treatment and the rate of apoptosis in vitro, and also
      analyzed Bcl-2 and Fas expression on peripheral blood mononuclear cells (PBMC)
      from patients with SLE in relation to GC-induced apoptosis. METHODS: Twenty-seven
      SLE patients and 13 normal controls were studied. Disease activity scores were
      determined before and after treatment and used to divide patients into 2 groups:
      GC-resistant and GC-responsive. Isolated PBMC were stimulated with anti-CD3
      monoclonal antibodies, cultured with various concentrations of GC, and analyzed
      by alamar blue assay to determine the LC50, defined as the concentration of GC
      lethal to 50% of the cells. We measured the expression of CD4, CD8, Fas, and Bcl
      2 by FACStar plus flow cytometry. RESULTS: Lymphocytes in the GC-resistant group
      of SLE patients showed a significantly lower percentage of GC-induced apoptotic
      cells than did lymphocytes from the responsive group or from normal controls. The
      LC50 in the resistant group was significantly higher than that in normal controls
      or the responsive group. The lymphocytes remaining in the resistant group after
      GC treatment were mainly CD8+, with a high expression of Bcl-2. There was no
      significant difference in Fas expression between the GC-responsive and GC
      resistant groups. CONCLUSION: Determination of the LC50 may be useful in
      predicting the efficacy of GC treatment in SLE patients, and may be of use in
      considering other treatment options. CD8 and Bcl-2 double-positive lymphocytes
      that are insensitive to the apoptotic effect of GCs may play a role in the
      resistance to these agents in SLE patients.

PMID- 9588734
TI  - Risk factors for ovarian failure in patients with systemic lupus erythematosus
      receiving cyclophosphamide therapy.
AB  - OBJECTIVE: To determine the incidence of ovarian failure after cyclophosphamide
      (CYC) treatment for systemic lupus erythematosus (SLE) and to identify the risk
      factors for this complication. METHODS: The records of 70 premenopausal female
      SLE patients treated with CYC were reviewed retrospectively. Information on
      demographic features, autoantibody profiles, and CYC treatment was obtained, and
      comparisons were made between those who developed ovarian failure and those who
      did not. Data on the CYC-treated patients were also compared with data on 2
      control groups of non-CYC-treated SLE patients. RESULTS: Eighteen patients
      developed ovarian failure after CYC treatment, for an overall incidence of 26%.
      The incidence of ovarian failure showed a linear trend of increase with
      increasing age at the start of CYC (P = 0.007). The cumulative CYC dose was
      significantly higher in the patients with ovarian failure than in those without
      (28.3 gm versus 15.4 gm; P = 0.004). The risk of ovarian failure also showed a
      linear trend of increase with increasing cumulative CYC dose (P < 0.001). Using
      multiple logistic regression, the age at the time of CYC treatment initiation
      (beta = 0.37, SE = 0.11, P = 0.001) and the cumulative dose of CYC received (beta
      = 0.69, SE = 0.29, P = 0.02) were found to be independent risk factors for CYC
      induced ovarian failure. CONCLUSION: In our population of female SLE patients,
      CYC-induced ovarian toxicity is a significant problem, particularly in patients
      above the age of 40. The age at the start of CYC therapy and the cumulative dose
      are the major determinants for the development of this complication. For older
      patients with SLE in whom the use of CYC is warranted, a shorter course and lower
      dosage should be considered.

PMID- 9588735
TI  - Decreased production of interleukin-12 and other Th1-type cytokines in patients
      with recent-onset systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the profile of Th1-type and Th2-type cytokines produced
      by mononuclear cells from patients with recent-onset systemic lupus erythematosus
      (SLE), prior to the initiation of treatment with corticosteroids. METHODS: Using
      sensitive radioimmunoassays, interleukin-4 (IL-4), IL-10, IL-12 p40, tumor
      necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma), and granulocyte
      macrophage colony-stimulating factor (GM-CSF) released into the culture
      supernatants of various unstimulated and stimulated blood mononuclear cell
      populations from 10 SLE patients was assessed in comparison with 10 matched
      healthy controls studied in parallel. RESULTS: In early SLE, monocyte-enriched
      cells constitutively produced increased amounts of IL-10 and decreased amounts of
      IL-12 following stimulation. Lymphocyte-enriched cells in SLE produced decreased
      amounts of IFN gamma and TNF alpha following stimulation. In "rested" cells,
      these defects were accentuated and a defect in IL-12 production was suggested.
      Depletion studies suggested that CD8+ cells were a major source of TNF alpha and
      IFN gamma in controls, but not in SLE patients. Increased IL-4 production or
      abnormalities in GM-CSF production were not observed. CONCLUSION: This study
      suggests that even early in the course of SLE, monocyte production of IL-10 is
      increased and that of IL-12 is decreased. Decreased production of Th1-type
      cytokines in SLE may be secondary to this imbalance between IL-10 and IL-12. A
      contributory role of dysfunctional CD8+ cells is suggested.

PMID- 9588736
TI  - Lack of correlation between the detection of Chlamydia trachomatis DNA in
      synovial fluid from patients with a range of rheumatic diseases and the presence
      of an antichlamydial immune response.
AB  - OBJECTIVE: To resolve how frequently Chlamydia trachomatis and Chlamydia
      pneumoniae DNA are present in the joints of unselected patients with reactive
      arthritis (ReA) and undifferentiated oligoarthritis, and to determine if there is
      an accompanying serologic or cellular antichlamydial immune response. METHODS:
      Two polymerase chain reaction (PCR) protocols to detect the plasmid of C.
      trachomatis and the outer membrane protein 1 gene of C. pneumoniae were developed
      for specific use with synovial fluid (SF). Subsequently, the assays were used to
      detect DNA from the 2 organisms in SF from 54 adult patients with rheumatic
      diseases, including 4 with sexually acquired ReA and 31 with undifferentiated
      oligoarthritis. The presence of chlamydial antibodies and SF lymphocyte
      proliferation responses were determined in parallel. RESULTS: The PCR protocols
      were species-specific and highly sensitive. SF samples from 15 patients (8 with
      undifferentiated oligoarthritis, 3 with ReA, 1 with rheumatoid arthritis, and 1
      with psoriatic arthritis) were positive for C. trachomatis. There was no
      significant correlation between the presence of C. trachomatis DNA in the joint
      and a Chlamydia-specific synovial T cell response or a serologic response. C.
      pneumoniae was not detected in any of the 54 patients, although it was identified
      in the SF from a rheumatoid arthritis patient outside this study, demonstrating
      that the assay was capable of detecting the organism in the joint. CONCLUSION: C.
      trachomatis DNA was present in ReA patients and in nearly one-third of unselected
      patients with undifferentiated oligoarthritis, which further supports the
      hypothesis that it plays an important role in disease pathogenesis. However, its
      presence did not correlate with evidence of an antichlamydial immune response.
      Despite previous anecdotal reports, C. pneumoniae does not appear to be a major
      cause of undifferentiated oligoarthritis or ReA.

PMID- 9588737
TI  - Persistence of Yersinia antigens in peripheral blood cells from patients with
      Yersinia enterocolitica O:3 infection with or without reactive arthritis.
AB  - OBJECTIVE: To assess the persistence of bacterial antigens in peripheral blood
      cells from patients with Yersinia enterocolitica O:3-triggered reactive arthritis
      (ReA). METHODS: Peripheral blood samples were obtained from 20 patients with Y.
      enterocolitica O:3 infection (11 with ReA and 9 without). These samples were
      studied by immunochemical techniques for the presence of Yersinia antigens at the
      beginning of infection and up to 4 years thereafter. Synovial fluid samples from
      6 of the 11 ReA patients were also studied. RESULTS: The Yersinia antigens
      lipopolysaccharide and heat-shock protein (HSP) were detected in peripheral blood
      mononuclear cells and polymorphonuclear phagocytes from all patients studied at
      the early phase of the disease. They were also found in the synovial fluid cells
      of patients with Yersinia-triggered ReA. At 4 years after the onset of infection,
      these bacterial antigens were still detected in the peripheral blood cells of
      most of the ReA patients studied. CONCLUSION: This study has, for the first time,
      directly demonstrated that bacterial antigens persist for a long time in patients
      who develop ReA after Y. enterocolitica O:3 infection. The finding of bacterial
      HSP in synovial fluid cells could provide a link to the pathogenesis of ReA,
      since T cell responses of synovial cells have been shown to be directed against
      that structure. A close similarity between the bacterial and host HSP might
      contribute to the development of the relatively common, chronic form of this
      complication.

PMID- 9588738
TI  - Prevalence of the diffuse infiltrative lymphocytosis syndrome among human
      immunodeficiency virus type 1-positive outpatients.
AB  - OBJECTIVE: To ascertain the prevalence of the diffuse infiltrative lymphocytosis
      syndrome (DILS) in human immunodeficiency virus type 1 (HIV-1)-positive
      outpatients. METHODS: The presence of sicca symptoms and visible salivary gland
      enlargement was determined by interview and physical examination, and the
      clinical stage was determined by chart review, in 523 HIV-positive patients. The
      diagnosis of DILS was established in those with parotid gland enlargement by
      minor salivary gland biopsy or radionuclide scintigraphy. RESULTS: Definite DILS
      was found in 15 (3%) of the 523 patients, and possible DILS in 18 (3.4%). The
      prevalence of definite DILS was significantly higher in African Americans (4.5%).
      Self-reported facial swelling and xerophthalmia that was not explained by the
      effects of medication were found more frequently in those with DILS than in the
      non-DILS patients. Patients with DILS had higher CD8 counts (mean +/- SD 1,456 +/
      813/mm3) compared with those without DILS (934 +/- 624/mm3; P < 1 x 10(-6)), and
      were less advanced in their HIV clinical stage (Centers for Disease Control and
      Prevention stages A or B in 76% compared with 60% of the non-DILS group; P =
      0.01). CONCLUSION: DILS is an important problem in HIV-infected outpatients and
      tends to occur in patients whose clinical disease is at a less advanced stage.
      Patients with parotid gland enlargement accompanied by sicca symptoms should be
      screened for HIV infection.

PMID- 9588739
TI  - Clinical image: cutaneous ulceration in type II cryoglobulinemia.

PMID- 9588740
TI  - Inhibition of activator protein 1 activity by paclitaxel suppresses interleukin-1
      induced collagenase and stromelysin expression by bovine chondrocytes.
AB  - OBJECTIVE: Cytokine-induced collagenase 1 (matrix metalloproteinase 1 [MMP-1])
      and stromelysin 1 (MMP-3) expression is dependent on activator protein 1 (AP-1)
      activation and have a fundamental role in the pathophysiology of arthritic
      diseases by degrading connective tissues. This study evaluates the effect of
      paclitaxel on AP-1 activation and examines its effect on the expression of 2
      major matrix metalloproteinases, MMP-1 and MMP-3, and its effect on AP-1
      activation. METHODS: MMP-1, MMP-3, c-fos, and c-jun messenger RNA (mRNA) levels
      were measured in interleukin-1 (IL-1)-induced primary chondrocytes in the
      presence and absence of paclitaxel. The effect of paclitaxel on AP-1 promoter
      activity was studied by chloramphenicol acetyltransferase assays in IL-1
      stimulated chondrocytes. The same conditions were applied to studies of the
      effect of paclitaxel on binding at the AP-1 site by gel-shift mobility assays.
      The cytotoxicity effect of paclitaxel on chondrocytes was studied by examining
      cell viability and expression of the matrix molecules aggrecan and type II
      collagen. RESULTS: IL-1-induced MMP-1 and MMP-3 mRNA levels were markedly reduced
      in paclitaxel-treated chondrocytes. Further, IL-1-induced AP-1 activation and AP
      1 binding were inhibited by paclitaxel. However, there was no effect on the
      expression of c-fos or c-jun mRNA levels. Chondrocyte viability was not affected
      by paclitaxel, and there was no effect on the expression of housekeeping genes or
      the major cartilage matrix molecules aggrecan and type II collagen. CONCLUSION:
      These studies demonstrate that paclitaxel is a potent inhibitor of MMP-1 and MMP
      3 synthesis through the AP-1 site. However, inhibition of AP-1 activity by
      paclitaxel does not affect the viability of chondrocytes or the expression of
      matrix molecules.

PMID- 9588741
TI  - Collagenase 1 and collagenase 3 expression in a guinea pig model of
      osteoarthritis.
AB  - OBJECTIVE: To analyze the in vivo compartmental expression of collagenases 1 and
      3 (MMP-1 and MMP-13) in the Hartley guinea pig model of spontaneously occurring
      osteoarthritis (OA) for the purpose of elucidating their roles in the
      pathogenesis of OA. METHODS: Competitive reverse transcription-polymerase chain
      reaction (RT-PCR) and immunohistochemistry quantification of messenger RNA (mRNA)
      and protein levels in medial and lateral tibial cartilage obtained from the knee
      joints of 2-month-old (no OA) and 12-month-old (OA) guinea pigs. RESULTS: The
      patterns of mRNA expression of collagenases 1 and 3 varied with the age of the
      animal and the compartment of the knee. We also found focal areas of collagenase
      1 and collagenase 3 proteins localized to the extracellular matrix of OA lesion
      sites, coincident with three-quarter/one-quarter collagen cleavage. Collagenase 3
      protein was also abundant throughout the medial tibial cartilage of 2-month-old
      animals. CONCLUSION: This represents the first description of bona fide
      collagenase 1 in a rodent species. Recent evidence, however, based on analysis of
      mitochondrial DNA homologies, suggests that the guinea pig is not a member of the
      order Rodentia and may be more closely allied with lagomorphs. This taxonomic
      controversy leaves open to question the issue of the expression of collagenase 1
      in other rodents, such as mice and rats. The presence of active collagenases 1
      and 3 at OA lesion sites is consistent with an important role of these enzymes in
      the cartilage degradation of OA in guinea pigs. The expression of collagenase 3
      in medial tibial cartilage from 2-month-old guinea pigs may signify a role of
      this enzyme in cartilage remodeling with growth and development, or it may
      represent an early molecular manifestation of OA.

PMID- 9588742
TI  - Osteoblast-like cells from human subchondral osteoarthritic bone demonstrate an
      altered phenotype in vitro: possible role in subchondral bone sclerosis.
AB  - OBJECTIVE: Osteoarthritis (OA) is accompanied by subchondral bone sclerosis. The
      present study was undertaken to determine whether osteoblast-like cells in
      patients with OA show an abnormal phenotype that could contribute to this
      sclerosis. METHODS: Explants and primary in vitro osteoblast-like cell cultures
      were prepared from subchondral bone specimens from OA patients or from bone
      removed at autopsy from individuals showing no signs of OA or metabolic bone
      disease. We measured the abundance and activity of urokinase plasminogen
      activator (uPA), and the levels of PA inhibitor (PAI-1) and insulin-like growth
      factor 1 (IGF-1) in conditioned media from both explants and osteoblast-like
      cells. The expression of osteoblast phenotypic biomarkers was also evaluated.
      RESULTS: OA explants showed increased levels and activity of uPA, no changes in
      PAI-1 abundance, and increases in IGF-1 release, as compared with preparations
      from normal individuals. In vitro primary osteoblast-like cells showed results
      similar to the ex vivo findings for uPA, PAI-1, and IGF-1. Primary OA osteoblast
      like cells also expressed higher alkaline phosphatase activity and osteocalcin
      release than normal cells, both under basal conditions and with 1,25(OH)2D3 (1,25
      dihydroxyvitamin D) stimulation. Conversely, OA osteoblast-like cells showed
      blunted cAMP synthesis in response to human parathyroid hormone and prostaglandin
      E2 in contrast to the finding with normal osteoblast-like cells, a result that
      could not be attributed to altered adenylate cyclase activity. CONCLUSION: Ex
      vivo and in vitro results indicate similar altered activities of OA osteoblasts
      as compared with normal cells. This suggests that an altered phenotype of
      subchondral osteoblasts may be a contributing factor in human OA.

PMID- 9588743
TI  - The murine homolog of the interleukin-8 receptor CXCR-2 is essential for the
      occurrence of neutrophilic inflammation in the air pouch model of acute urate
      crystal-induced gouty synovitis.
AB  - OBJECTIVE: Acute neutrophil-dependent inflammation is central to acute gout.
      Urate crystals induce different classes of neutrophil chemotaxins, including
      certain chemokines (e.g., interleukin-8 [IL-8], growth-related oncogene alpha
      [GROalpha]) that share CXCR-2 as a receptor. This study was undertaken to assess
      the role of CXCR-2 ligands in a model of acute gout. METHODS: Urate crystals were
      injected into subcutaneous air pouches in mice that expressed or lacked the
      murine CXCR-2 homolog (mIL-8RH), and the development of neutrophilic inflammation
      was assessed. RESULTS: In normal mice, urate crystals induced a 10-fold increase
      (P < 0.01) in pouch fluid leukocytes (principally neutrophils) at 4 hours.
      Leukocytes adhered to the pouch lining, where crystals, the mIL-8RH ligand
      KC/GROalpha, and cells bearing mIL-8RH were abundant. In mIL-8RH(-/-) mice, urate
      crystals induced a proteinaceous leukocyte-poor exudate at 4 hours, despite
      crystal-induced activation of resident cells (documented by KC/GROalpha
      expression). CONCLUSION: Chemokines that bind the IL-8 receptor CXCR-2 are
      essential for the development of acute neutrophilic inflammation in response to
      urate crystals in the subcutaneous air pouch model.

PMID- 9588744
TI  - Involvement of macrophage migration inhibitory factor in the evolution of rat
      adjuvant arthritis.
AB  - OBJECTIVE: Recent studies have established an essential role for macrophage
      migration inhibitory factor (MIF) in T cell and macrophage activation, both of
      which are characteristics of rat adjuvant arthritis. This study investigated the
      role of MIF in early adjuvant arthritis. METHODS: MIF was detected in rat
      synovium by immunohistochemistry and enzyme-linked immunosorbent assay using
      specific monoclonal antibodies (MAb). Anti-MIF MAb treatment was administered,
      and the effects on clinical aspects of adjuvant arthritis were assessed. RESULTS:
      MIF was absent from normal rat synovium prior to adjuvant injection, but was
      detectable on day 4 after injection (6 days before the onset of clinical disease)
      and was colocalized with ED-1+ macrophages throughout the evolution of the
      disease. Levels of MIF were increased in established adjuvant arthritis sera, and
      adjuvant arthritis synovial macrophages released MIF at a mean +/- SEM
      concentration of 607.9 +/- 201.5 pg/ml. Anti-MIF treatment led to profound, dose
      dependent inhibition of the adjuvant arthritis clinical score, paw swelling, and
      synovial lavage leukocyte numbers (P < 0.001), and also resulted in reduced
      synovial macrophage and T cell accumulation. CONCLUSION: These findings
      demonstrate an important role for MIF in the evolution of rat adjuvant arthritis.

PMID- 9588745
TI  - Zinc is an essential cofactor for recognition of the DNA binding domain of
      poly(ADP-ribose) polymerase by antibodies in autoimmune rheumatic and bowel
      diseases.
AB  - OBJECTIVE: To characterize autoantibody response to poly(ADP-ribose) polymerase
      (PARP) and to assess the significance of autoantibodies to the 2 zinc fingers of
      this enzyme in patients with autoimmune rheumatic and bowel diseases. METHODS:
      The specificity of antienzyme autoantibodies was established by dot immunoassay
      with recombinant human PARP and by enzyme-linked immunosorbent assay using the
      recombinant N-terminal fragment containing the DNA binding domain of PARP, the
      recombinant C-terminal catalytic domain (40-kd fragment), a peptide containing
      the nuclear localization signal (NLS) of PARP, 2 synthetic peptides (and mutated
      peptides) corresponding to zinc-finger motifs F1 and F2 that are present in the
      DNA binding domain, zinc fingers from other self antigens (e.g., peptides from
      Ro60, Ro52, and U1C proteins), and poly(ADP-ribose). Sera from patients with
      autoimmune rheumatic and bowel diseases were tested, as were affinity-purified
      antibodies. Histocompatibility typing of systemic lupus erythematosus (SLE)
      patients was performed by serology. RESULTS: Antibodies from the patient sera
      reacted only weakly with the recombinant N- and C-terminal domains and with the
      NLS peptide. In contrast, the 2 synthetic peptides corresponding to zinc-finger
      motifs F1 and F2 represented immunodominant targets for IgG antibodies from
      patients with SLE, mixed connective tissue disease (MCTD), Crohn's disease, and
      ulcerative colitis. The sera from patients with SLE and MCTD showed much weaker
      reactivity with mutant peptides F1 and F2, which contain mutations at the
      cysteine residues involved in zinc coordination. F1/F2 antibodies did not cross
      react with zinc fingers from other self proteins. No correlation was found
      between the presence of F1/F2 autoantibodies in SLE sera and the presence of
      other autoantibodies typical of this disease (e.g., anti-double-stranded DNA and
      poly[ADP-ribose] antibodies). The presence of F2 antibodies in the serum of SLE
      patients was negatively associated with HLA-DR6. CONCLUSION: An autoimmune
      response to PARP is potentially important because this enzyme is involved in DNA
      repair and is rapidly cleaved during the "execution phase" of apoptosis. The high
      prevalence in certain autoimmune rheumatic and bowel diseases of antibodies to F1
      and F2, which are directly involved in this process, is further evidence
      implicating involvement of the DNA repair system in chronic inflammatory
      diseases.

PMID- 9588746
TI  - Polymorphisms of HLA class II genes and autoimmune responses to Ro/SS-A-La/SS-B
      among Japanese subjects.
AB  - OBJECTIVE: To investigate HLA class II allele associations with autoantibody
      responses to Ro/SS-A and La/SS-B among Japanese subjects. METHODS: Haplotype and
      allele distributions, along with molecular polymorphisms, of HLA class II genes
      were analyzed by polymerase chain reaction-restriction fragment length
      polymorphism in 41 Japanese women with precipitating autoantibodies to Ro/SS-A
      and/or La/SS-B. RESULTS: Among women with both Ro/SS-A and La/SS-B antibodies,
      the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele
      showed significantly increased frequencies compared with patients with anti-Ro/SS
      A alone or with normal controls. All women with both anti-Ro/SS-A and anti-La/SS
      B, but not those with anti-Ro/SS-A alone, carried DRB1 alleles that shared the
      same amino acid residues at positions 14-31 and 71 of the hypervariable regions
      of the DRB1 chain. All anti-Ro/SS-A positive women carried 1 or 2 alleles of
      DQB1*06 and DQB1*03 subtypes that shared the same amino acid residues at
      positions 71-77 of the DQB1 chain. HLA class II allele distributions did not
      differ among 3 anti-Ro/SS-A positive groups with different disease expressions,
      i.e., patients with systemic lupus erythematosus, patients with primary Sjogren's
      syndrome, and women with no apparent symptoms of rheumatic disease. CONCLUSION:
      HLA class II allele distributions differ among anti-Ro/SS-A positive subjects
      according to the presence or absence of coexisting anti-La/SS-B antibodies, but
      not according to disease expression. Our findings suggest that different HLA
      class II molecules might control the development of anti-Ro/SS-A and/or anti
      La/SS-B antibodies in the autoimmune response to the Ro/SS-A-La/SS-B complex.

PMID- 9588747
TI  - Segmental mediolytic arteriopathy of the splenic and hepatic arteries mimicking
      systemic necrotizing vasculitis.
AB  - Segmental mediolytic arteriopathy, a rare, noninflammatory arterial disease, is
      fundamentally a variant of fibromuscular dysplasia. The characteristic
      angiographic findings of segmental mediolytic arteriopathy include the "string of
      beads" and microaneurysms which are indistinguishable from those of vasculitis,
      and the correct diagnosis can be made only after histopathologic evaluation of
      the arterial lesions. Thrombosis, arterial wall hemorrhage, and dissection are
      among the complications of segmental mediolytic arteriopathy. We describe herein
      a patient with segmental mediolytic arteriopathy who presented with
      hemoperitoneum. The patient underwent urgent surgical repair of a ruptured
      hepatic artery aneurysm. The postoperative visceral arteriography findings led to
      a clinical diagnosis of polyarteritis nodosa, and immunosuppressive therapy was
      initiated. This treatment was stopped as soon as the correct biopsy diagnosis of
      segmental mediolytic arteriopathy was obtained through outside consultation. The
      patient recovered without drug treatment and was spared the potentially life
      threatening complications of immunosuppression.

PMID- 9588748
TI  - Pseudogout following intraarticular injection of sodium hyaluronate.

PMID- 9588749
TI  - The polymorphic CYP17 allele is not found with increased frequency in systemic
      lupus erythematosus.

PMID- 9588750
TI  - The original "DAS" and the "DAS28" are not interchangeable: comment on the
      articles by Prevoo et al.

PMID- 9588751
TI  - Long-term outcome of total lymphoid irradiation in rheumatoid arthritis: comment
      on the article by Westhovens et al.

PMID- 9588752
TI  - HLA-DMA and DMB genes in rheumatoid arthritis: comment on the article by Pinet et
      al.

PMID- 9588753
TI  - Collagen crosslinks in fibromyalgia: comment on the article by Sprott et al.

PMID- 9588754
TI  - HLA-B27 and the spondylarthropathies in Lebanon: comment on the article by Awada
      et al.

PMID- 9588755
TI  - Does knuckle cracking lead to arthritis of the fingers?

PMID- 9588756
TI  - The influence of L-NG-nitroarginine methyl ester, an inhibitor of nitric oxide
      synthase, upon the anticonvulsive activity of conventional antiepileptic drugs
      against maximal electroshock in mice.
AB  - NG-Nitro-L-arginine methyl ester (L-NAME, an unspecific nitric oxide synthase
      inhibitor), applied at 1 and 40 mg/kg, did not influence the electroconvulsive
      threshold, but impaired the anticonvulsant activity of valproate (at 40 mg/kg)
      and phenobarbital (at 1 and 40 mg/kg). No effect was observed in the case of
      carbamazepine and diphenylhydantoin. The effect of L-NAME upon the protective
      activity of phenobarbital was not reversed by L-arginine (500 mg/kg), a source of
      endogenous nitric oxide. Moreover, this nitric oxide synthase inhibitor did not
      alter the plasma levels of antiepileptic drugs studied, so a pharmacokinetic
      interaction is not probable. L-NAME per se (40 mg/kg) caused a moderate motor
      impairment but did not affect long-term memory. The combined treatment of L-NAME
      and antiepileptic drugs (providing a 50% protection against maximal electroshock)
      resulted in motor disturbances. On the other hand, mice performed the memory task
      better upon combined treatment of antiepileptic drugs with L-NAME compared to
      antiepileptic drugs alone. A 4-day administration of L-NAME, similarly to acute
      injections, decreased the protective action of phenobarbital but not that of
      diphenylhydantoin. The results indicate that L-NAME is able to reduce the
      protective activity of some conventional antiepileptics and this effect may be
      not associated with impaired synthesis of nitric oxide.

PMID- 9588757
TI  - Changes in high K+-evoked serotonin release and serotonin 2A/2C receptor binding
      in the frontal cortex of rats with thioacetamide-induced hepatic encephalopathy.
AB  - Serotonergic systems were investigated in the frontal cortex of rats with
      thioacetamide (TAA)-induced acute hepatic encephalopathy (HE). Extracellular
      basal levels of 5-HT showed no difference between control and HE animals, whereas
      the levels of 5-HIAA were significantly increased in HE rats. Unlike basal
      levels, high K+-evoked 5-HT release was significantly higher in HE rats than
      controls. Bmax of (+/-)-1-(2,5-dimethoxy-4-[125I] iodophenyl)-2-aminopropane
      ([125I] DOI) binding, mainly labeling postsynaptic 5-HT2A receptors, was
      significantly decreased without any change in Kd in HE rats. These results
      suggest that there is no change in basal 5-HT release in the cortex of rats with
      TAA-induced HE despite the increase in intraneuronal 5-HT metabolism and in the
      size of releasable 5-HT pool, and that serotonergic neurotransmission via 5-HT2A
      receptor is altered in the brain area of rats with HE.

PMID- 9588758
TI  - Augmentation of lithium's behavioral effect by inositol uptake inhibitors.
AB  - Lithium inhibits the enzyme inositol monophosphatase and thus obstructs the
      enzymatic degradation of inositol triphosphate (IP3) to inositol in the phosphate
      phosphoinositide (PIP) cycle. This inhibition may result in reduced availability
      of the second messengers IP3 and DAG that are derivates of the PIP cycle, and
      this action is currently a leading hypothesis regarding lithium's therapeutic and
      prophylactic effect in affective disorders. Inositol is also available to the
      cell by uptake from the intercellular matrix, and therefore it is possible that
      compounds that block the uptake may have lithium-like effects. To test this
      hypothesis, the present study evaluates the effects of two inositol uptake
      inhibitors, the carbohydrate L-fucose and the cyclodepsipeptide nordidemnin, in a
      behavioral model of pilocarpine-induced seizures known to be enhanced by lithium.
      We tested the possibility that L-fucose produces lithium-like effects, or that L
      fucose or nordidemnin augment lithium's behavioral effects. Results indicate that
      acute ICV treatment with L-fucose did not by itself have a lithium-like effect in
      the behavioral model, but significantly augmented lithium's effect when combined
      with lithium treatment. Nordidemnin treatment showed similar effects. The results
      suggest that when inositol monophosphatase is inhibited by lithium, further
      restriction of cellular inositol availability may result in an augmentation of
      lithium's behavioral effects. It is possible that such manipulations may be
      applicable in the treatment of patients with affective disorders, especially
      patients who are poor responders to lithium monotherapy.

PMID- 9588759
TI  - Levels and proteolytic processing of chromogranin A and B and secretogranin II in
      cerebrospinal fluid in neurological diseases.
AB  - Human cerebrospinal fluid (CSF) contains chromogranin A and B and secretogranin
      II which represent peptides secreted from neuronal large dense core vesicles.
      Within these vesicles these precursor peptides are at least partly processed to
      smaller peptides. We analysed the CSF levels of chromogranins/secretogranin by
      radioimmunoassay using specific antisera. The degree of their processing was
      characterized by molecular sieve column chromatography followed by
      radioimmunoassay. As previously shown secretogranin II is fully processed to
      smaller peptides including the peptide secretoneurin, whereas processing of
      chromogranin A was more limited. For chromogranin B we found in this study a high
      degree of processing comparable to that of secretogranin II. An analysis of CSF
      from patients with multiple sclerosis, essential tremor, Alzheimer and Parkinson
      disease, did not reveal any differences in proteolytic processing of
      chromogranins/secretogranin when compared to control CSF. We conclude that in the
      four diseases investigated there is no change in the proteolytic processing of
      the chromogranins/secretogranin within the large dense core vesicles. The
      absolute levels of chromogranins/secretogranin varied in CSF collected in
      different hospitals, however their relative ratios were remarkable constant. We
      suggest to use this ratio as a parameter to standardise CSF levels of other
      peptides, e.g. neuropeptides. In Parkinson patients the chromogranin
      A/secretogranin II ratio was significantly increased whereas in Alzheimer
      patients and those with essential tremor and multiple sclerosis no change of the
      ratios was observed. Apparently there are only limited changes in the
      biosynthesis, processing, secretion and CSF clearance of these peptides in
      pathological conditions.

PMID- 9588760
TI  - Age-related changes in the cerebrospinal fluid level of beta-endorphin and
      substance P. Short communication.
AB  - To evaluate the early age-related changes in neuropeptides, we have measured the
      cerebrospinal fluid (CSF) levels of beta-endorphin and substance P in young
      patients over a range of ages. Specimens of CSF were obtained from 39
      neurologically normal children, aged 1 month to 10 years of age, and in 9 adult
      controls. CSF levels of both neuropeptides were observed to peak during the first
      year of life, and showed a negative correlation with increasing age. A
      significant positive correlation was observed between the CSF level of beta
      endorphin and that of substance P.

PMID- 9588761
TI  - Increased blood mercury levels in patients with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a common neurodegenerative disorder that leads to
      dementia and death. In addition to several genetic parameters, various
      environmental factors may influence the risk of getting AD. In order to test
      whether blood levels of the heavy metal mercury are increased in AD, we measured
      blood mercury concentrations in AD patients (n = 33), and compared them to age
      matched control patients with major depression (MD) (n = 45), as well as to an
      additional control group of patients with various non-psychiatric disorders (n =
      65). Blood mercury levels were more than two-fold higher in AD patients as
      compared to both control groups (p = 0.0005, and p = 0.0000, respectively). In
      early onset AD patients (n = 13), blood mercury levels were almost three-fold
      higher as compared to controls (p = 0.0002, and p = 0.0000, respectively). These
      increases were unrelated to the patients' dental status. Linear regression
      analysis of blood mercury concentrations and CSF levels of amyloid beta-peptide
      (A beta) revealed a significant correlation of these measures in AD patients (n =
      15, r = 0.7440, p = 0.0015, Pearson type of correlation). These results
      demonstrate elevated blood levels of mercury in AD, and they suggest that this
      increase of mercury levels is associated with high CSF levels of A beta, whereas
      tau levels were unrelated. Possible explanations of increased blood mercury
      levels in AD include yet unidentified environmental sources or release from brain
      tissue with the advance in neuronal death.

PMID- 9588762
TI  - Subcellular distribution of protein phosphatases and abnormally phosphorylated
      tau in the temporal cortex from Alzheimer's disease and control brains.
AB  - Microtubule-associated protein tau is abnormally hyperphosphorylated in the brain
      of patients with Alzheimer's disease (AD). In vitro studies have shown that
      protein phosphatases PP-2A and PP-2B can convert Alzheimer like tau to its normal
      state and that the activities of PP-1, PP-2A, and phosphotyrosyl-protein
      phosphatase (PTP) are reduced in AD brain. However, to have a direct effect on
      the regulation of phosphorylation on tau, these enzymes have to exist in neurons.
      Using specific polyclonal antibodies the levels of protein phosphatases PP-1, PP
      2A, and PP-2B were determined by indirect ELISA in superior temporal cortical
      gray matter of AD and control brains. The protein levels of PP-2A and PP-2B were
      significantly increased in postsynaptosomal supernatant 2 (S2) of the AD group,
      and this alteration showed a significant linear correlation with levels of
      hyperphosphorylated tau. PP-1 and PTP-1B levels were not significantly changed in
      any of the AD fractions. Because of the large variation from case to case, the
      activity levels of none of the phosphatases investigated were significantly
      different between the AD and control groups. However, the PP-2B specific activity
      (activity/protein) showed a significant linear inverse correlation with
      hyperphosphorylated tau. These studies suggest that any attempt by the AD brain
      to compensate for the decreased tau phosphatase activity remains unsuccessful and
      that the decrease in phosphatase activity might contribute to increased levels of
      abnormally phosphorylated tau.

PMID- 9588763
TI  - Neurotrophic factors and the maldevelopmental hypothesis of schizophrenic
      psychoses. Review article.
AB  - The maldevelopmental model of schizophrenia postulates pathological alterations
      in embryonal neurogenesis as the etiopathogenetic basis of schizophrenic
      psychosis; the neurotrophic factor hypothesis explains these changes as the
      result of disturbances of processes involving the trophic factors.
      Neurotransmitter deficits are thereby interpreted as epiphenomena of underlying
      neurotrophic factor deficacy. The functional systems of the various neurotrophic
      factors are characterized by complex interaction mechanisms. Both primary genetic
      alterations, and secondary impairments, induced by exogene noxae, of the
      receptors and signal transducers associated with neurotrophic factors, as well as
      of the neurotrophic factors themselves are possible. Preliminary clinical studies
      indicate that schizophrenic psychoses may be associated with changes in the
      genetic code of certain neurotrophic factors. Various phenomena typical of the
      schizophrenic psychoses can be interpreted according to the neurotrophic factor
      hypothesis.

PMID- 9588764
TI  - Insertion/deletion variant (-141C Ins/Del) in the 5' regulatory region of the
      dopamine D2 receptor gene: lack of association with schizophrenia and bipolar
      affective disorder. Short communication.
AB  - A possible dysregulation of dopaminergic neurotransmission has been implicated in
      the aetiology of schizophrenic psychoses, in particular of paranoid-hallucinatory
      states, and of the manic episodes of bipolar affective disorder. In the present
      study we analysed allelic and genotypic variations of a recently described
      functional deletion/insertion variant (-141C Ins/Del) in the 5' flanking region
      of the human dopamine D2 receptor gene. We investigated a total of 620 unrelated
      individuals, comprising 260 schizophrenic patients, 70 patients with bipolar
      affective disorder, and 290 population controls. Analysis of the -141C Ins/Del
      variant revealed that the schizophrenic, bipolar affective and control groups did
      not differ significantly regarding genotype frequencies and allele frequencies.
      No evidence of an allelic association with either a family history of
      schizophrenic psychosis or a diagnosis of schizophrenia of the paranoid type
      (according to ICD 10) was found. Our findings indicate that the -141C Del variant
      in the 5' flanking region of the human dopamine D2 receptor gene is unlikely to
      play a substantial role in genetic predisposition to major psychiatric disorders
      in Caucasians.

PMID- 9588765
TI  - Chronic hepatitis B: interferon-monotherapy or combination with nucleoside
      analogues?

PMID- 9588766
TI  - The first decade of the transjugular intrahepatic portosystemic shunt (TIPS):
      state of the art.
AB  - The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional
      treatment resulting in decompression of the portal system by creation of a side
      to-side portosystemic anastomosis. Since its introduction 10 years ago, more than
      500 publications have appeared demonstrating rapid acceptance and increasing
      clinical use. This review summarizes the present knowledge of technical aspects
      and complications, follow-up of patients, and indications. With respect to the
      technique, the TIPS procedure is probably one of the most difficult interventions
      and, therefore, technical success and complications clearly depend on the skills
      of the operator. Thus, the number and kind of complications reported in this
      review do not necessarily relate to the procedural complications of an
      experienced center. The follow-up of the TIPS patient has to assess shunt
      patency, liver function and hepatic encephalopathy. Shunt patency can best be
      monitored by duplex-sonography. Routine radiological revision seems not to be
      helpful and does not improve results, i.e., rebleeding and survival. Short term
      patency may be improved by anticoagulation, while such a treatment does not
      influence long-term patency. With respect to the indications of TIPS, much is
      known about treatment of variceal bleeding. The nine randomized studies that are
      available to date show that survival is comparable between patients receiving
      TIPS or endoscopic treatment. The second group of patients is the group with
      refractory ascites and related complications, such as hepatorenal syndrome and
      hepatic hydrothorax. It has been demonstrated that TIPS improves these
      complications, but randomized studies are still lacking. In addition, TIPS has
      been applied successfully to patients with Budd-Chiari syndrome, portal vein
      thrombosis, before liver transplantation, and for the treatment of ectopic portal
      hypertensive bleeding.

PMID- 9588767
TI  - Isolation, culture and characterization of biliary epithelial cells from
      different anatomical levels of the intrahepatic and extrahepatic biliary tree
      from a mouse.
AB  - We developed methods to isolate biliary epithelial cells (BECs) from the
      gallbladder (GB), common bile duct (CBD), intrahepatic large bile duct (ILBD) and
      small bile duct (ISBD) of a mouse, simultaneously. ILBD and ISBD were cut from
      the biliary tree after collagenase perfusion of the liver. BECs from all of these
      biliary segments were cultured as explants on collagen gel. BECs spread from the
      explants and formed cellular sheets. Areas of these sheets composed entirely of
      BECs were cut and placed on other gels as subculture, and this continued for 10
      passages. Primary and passage cultured BECs on gel were composed of a monolayer
      of epithelial cells. Passaged cultured BECs in gel formed a spherical cyst lined
      by a single epithelial layer. Ultrastructurally, microvilli were dense on the
      luminal surface, and junctional complex and interdigitation was identifiable on
      the lateral surfaces. These features were similar in both primary and passaged
      cultured BECs, irrespective of their anatomical origin. Major histocompatibility
      complex antigens and intercellular adhesion molecule-1 were induced on the
      basolateral cell membranes of primary and passaged cultured BECs, by interferon
      gamma. Although several phenotypic, structural and probable biological features
      of BECs inherent to each anatomical level may be lost after culture on gel, a
      combination of this method, several immunological modifications in experimental
      animals, and addition of immunologically active substances to the culture medium
      will make the immunopathologic analysis of biliary diseases possible.

PMID- 9588768
TI  - Relationship between cellular shape and receptor-mediated endocytosis: an
      ultrastructural and morphometric study in rat Kupffer cells.
AB  - The relationship between cellular shape (i.e., size, volume, presence of
      microvilli, pseudopodia, flat or round shape) and receptor-mediated endocytotic
      activities (i.e., binding and internalization) was investigated using intact
      liver as well as freshly isolated Kupffer cells and Kupffer cells in culture. The
      morphological features of Kupffer cells were reconstructed by three-dimensional
      analysis from in situ experiments and by densitometric analysis of cells in
      suspension and in culture. By morphometry at the ultrastructural level, different
      cellular shapes were compared with the respective capacities for binding and
      internalization of glycoproteins with terminal galactosyl residues. The number of
      asialoglycoprotein-gold particles bound to the cell surface or internalized into
      endosomes was calculated. Our data show that differences in cellular shape,
      mainly related to the reduction of projection and microvilli and to the roundness
      of cell surface, accompany modulation of galactose-specific receptors in rat
      Kupffer cells, thus supporting the hypothesis that cell morphology is affected by
      endocytic activities. In fact, the progressive reduction in microvilli
      projections and cellular roundness is paralleled by the progressive decrement of
      both binding and uptake capacity from in situ, freshly isolated and cultured
      Kupffer cells.

PMID- 9588769
TI  - Hyperbaric oxygen pretreatment attenuates hepatic reperfusion injury.
AB  - Microcirculatory derangement, energy depletion and lipid peroxidation have been
      related to development of ischemia-reperfusion injury in the liver. This study
      investigates the effects of hyperbaric oxygen (HBO) on hepatic ischemia
      reperfusion injury. Adult, male Sprague-Dawley rats were used. Three groups were
      evaluated: 1) sham-operated control (laparotomy only, no ischemia, no HBO), n=8;
      2) ischemia control (1-h ischemia, 2-h reperfusion, no HBO), n=8; and 3) HBO
      pretreatment (100%, oxygen, 2.5 atm absolute, 90 min) plus ischemia (1-h
      ischemia, 2-h reperfusion), n=8. An in vivo microscope was used to investigate
      hepatic microcirculation. Tissue malondialdehyde (MDA) and adenosine triphosphate
      (ATP) were determined. In comparison with the ischemia control group, HBO
      significantly improved harmful insults following ischemia-reperfusion. HBO
      lessened adherent leukocyte count (6.00+/-1.31 cells/200 microm vs 11.38+/-2.88
      cells/200 microm), and improved flow velocity (1.72+/-0.26 mm/s vs 0.83+/-0.19
      mm/s) in post-sinusoidal venules. HBO also reduced MDA (1.04+/-0.24 nmol/mg
      protein vs 2.24+/-0.49 micromol/g protein), and increased ATP (2.03+/-0.17
      micromol/g wet wt vs 0.73+/-0.11 micromol/g wet wt) levels. This study
      demonstrates that HBO before ischemia may ameliorate the ischemia-reperfusion
      injury of the liver in the rat model.

PMID- 9588770
TI  - The Fas system is not significantly involved in apoptosis in human hepatocellular
      carcinoma.
AB  - We investigated the role of apoptosis in relation to proliferative activity in
      hepatocellular carcinoma (HCC) using in situ DNA nick end labeling (ISNEL) and
      immunostaining for the Ki-67 antigen in 35 patients with HCC. We also performed
      immunostaining for Fas and Fas ligand (Fas L) to determine the relationship
      between the Fas system and apoptosis. The ratio of the ISNEL labeling index (LI)
      to the Ki-67 LI was significantly lower in HCC than in surrounding nontumorous
      liver tissue (p<0.0001), suggesting that a decrease in apoptosis relative to cell
      proliferation is important in the pathogenesis of HCC. Fas and Fas L were
      expressed in both HCC and nontumorous tissue, but Fas and Fas L LIs were
      significantly lower in HCC (p<0.0001). Fas expression by cells near ISNEL
      positive cells tended to be increased in nontumorous tissue in mirror-image
      sections, suggesting that apoptosis is related to Fas expression. However, this
      pattern was rarely observed in HCC. These findings indicate that the Fas system
      may not play a major role in apoptosis in HCC.

PMID- 9588771
TI  - Absence of human herpesvirus 8 DNA sequences in vascular tumors of the liver.
AB  - Kaposi's sarcoma-associated herpes virus (KSHV), also designated human
      herpesvirus 8 (HHV8), has been detected consistently in Kaposi's sarcoma, body
      cavity lymphoma and multicentric Castleman's disease, both in human
      immunodeficiency virus (HIV)-positive and -negative patients. Identification of
      KSHV/HHV8 DNA sequences in various benign and malignant vascular tumors in HIV
      negative patients was reported in one study, but was not confirmed in several
      other studies. The vascular lesions, other than Kaposi's sarcoma, in which
      sequences could not be detected have included malignant vascular tumors of serous
      membranes, infantile capillary hemangiomas, and several benign and malignant
      vascular tumors of the spleen. We studied 30 primary benign and malignant
      vascular tumors of the liver; KSHV/HHV8 DNA sequences could not be detected in
      any. We conclude that this virus plays no role in the etiology of vascular tumors
      of the liver.

PMID- 9588772
TI  - Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology.
AB  - Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and
      both its biological features and its prognostic behavior are still under
      investigation. DNA content and proliferative activity of the tumor have been
      considered as biological parameters related to the tumor's aggressiveness. The
      present study attempts to investigate the possible association between histologic
      subtype, DNA content, and proliferative indices in HB. DNA content and the
      proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of
      HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed,
      paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA)
      labeling index was also evaluated by immunohistochemistry, and both the flow
      cytometry (FC) and the immunohistochemical data were correlated with tumor
      pathology. A significant association was found between histological type, DNA
      content and the percentage of cells in the S-phase, with aneuploidy and the
      highest proportions of S-phase cells significantly associated with embryonal
      tumors. The PCNA labeling index was found to be significantly higher in embryonal
      than in fetal phenotype. The biological heterogeneity of HB is Confirmed by the
      different nuclear content of the fetal (diploid) and embryonal (aneuploid)
      epithelial components of the tumor, also ruling out the likelihood of fetal
      (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since
      the highly proliferative neoplastic clones (i.e., embryonal) are thought to be
      more sensitive to antimitotic drugs, further studies are indicated to determine
      the relationship between ploidy, proliferative indices and chemoresponsiveness.

PMID- 9588773
TI  - Nucleoside analogue therapy in fibrosing cholestatic hepatitis--a case report in
      an HBsAg positive renal transplant recipient.
AB  - A 45-year-old HBsAg carrier (HBeAb positive with normal liver function tests)
      underwent renal transplantation for mesangioproliferative glomerulonephritis.
      Sixteen months later he developed jaundice. Investigations showed he remained
      HBeAb positive, but HBV-DNA levels were 99 pg/ml, indicating active replication
      of a HBV pre-core mutant. He was commenced on lamivudine therapy with a
      subsequent rapid fall in HBV-DNA levels to 2.8 pg/ml, but liver function tests
      continued to deteriorate and he developed hepatorenal failure. Liver biopsy
      showed fibrosing cholestatic hepatitis. He underwent liver transplantation, which
      was complicated by lactic acidosis. Lamivudine was withdrawn and HBV prophylaxis
      with HB immunoglobulin was commenced. Unfortunately he died 38 days post
      transplant of surgical complications with no evidence of HBV recurrence. We
      discuss the use of nucleoside analogues in fibrosing cholestatic hepatitis and
      review the literature.

PMID- 9588774
TI  - The adrenergic modulation of firings of respiratory rhythm-generating neurons in
      medulla-spinal cord preparation from newborn rat.
AB  - We analysed the modulation of respiratory neurons by adrenaline or noradrenaline
      (NA) in a newborn rat brainstem-spinal cord preparation. Adrenaline or NA caused
      a dose-dependent depression of the respiratory rhythm and induced C4 spinal tonic
      discharges. The inhibitory effect of adrenaline (ED50=0.5 microM) on the
      respiratory rhythm was stronger than NA (ED50=5 microM). The adrenaline
      respiratory rhythm depression was partially blocked by the alpha1-antagonist
      prazosin or by the alpha2-antagonist yohimbine. The C4 tonic discharge elicited
      by adrenaline was blocked by the alpha1-antagonist prazosin. The direct effects
      of adrenaline on pre-inspiratory (Pre-I) neurons were examined in a synaptic
      blockade solution (low Ca), and fifty-six percent of Pre-I neurons were found to
      continue firing. In low-Ca solution, Pre-I neurons were excited (n=29 of 39) or
      depressed (n=5 of 39) by adrenaline, and excited by alpha1-agonist phenylephrine
      or depressed by alpha2-agonist clonidine. These results suggest that the
      respiratory rhythm depression under intact network conditions is mediated by some
      other inhibitory system. The inhibitory effect of adrenaline on the respiratory
      rhythm was partially blocked by the GABA(A)-antagonists bicuculline or
      picrotoxin, but not by the GABA(B)-antagonist phaclofen. The present results
      suggest that: (1) respiratory rhythm generation is more sensitive to adrenaline
      than NA through alpha-adrenergic action of adrenaline; (2) the activity of Pre-I
      neurons could be directly regulated by excitation via alpha1-receptors and
      inhibition via alpha2-receptors; and (3) the depression of the respiratory rhythm
      by adrenaline is partly mediated by GABA(A)ergic neurons.

PMID- 9588775
TI  - Effect of eye movements on the magnitude of functional magnetic resonance imaging
      responses in extrastriate cortex during visual motion perception.
AB  - We have studied the effects of pursuit eye movements on the functional magnetic
      resonance imaging (fMRI) responses in extrastriate visual areas during visual
      motion perception. Echoplanar imaging of 10-12 image planes through visual cortex
      was acquired in nine subjects while they viewed sequences of random-dot motion.
      Images obtained during stimulation periods were compared with baseline images,
      where subjects viewed a blank field. In a subsidiary experiment, responses to
      moving dots, viewed under conditions of fixation or pursuit, were compared with
      those evoked by static dots. Eye movements were recorded with MR-compatible
      electro-oculographic (EOG) electrodes. Our findings show an enhanced level of
      activation (as indexed by blood-oxygen level-dependent contrast) during pursuit
      compared with fixation in two extrastriate areas. The results support earlier
      findings on a motion-specific area in lateral occipitotemporal cortex (human V5).
      They also point to a further site of activation in a region approximately 12 mm
      dorsal of V5. The fMRI response in V5 during pursuit is significantly enhanced.
      This increased response may represent additional processing demands required for
      the control of eye movements.

PMID- 9588776
TI  - Cortical control of presynaptic inhibition of Ia afferents in humans.
AB  - The effect of transcranial magnetic stimulation was investigated on presynaptic
      inhibition of Ia terminals in the human upper and lower limb. Presynaptic
      inhibition of Ia afferents was assessed by three different and independent
      methods: (1) heteronymous Ia facilitation of the H-reflex (assessing ongoing
      presynaptic inhibition of Ia afferents in the conditioning volley); (2) long
      lasting inhibition of the H-reflex by a group I volley (D1 inhibition, assessing
      presynaptic inhibition on Ia afferents in the test volley); (3) measurement of
      the monosynaptic Ia peak evoked in single motor units by a homonymous or
      heteronymous volley (post stimulus time histogram method). The first two methods
      were used on the lower limb; the last two on the upper limb. Provided that the
      corticospinal volley and the explored Ia volley were directed to the same target
      motoneurones, cortical stimulation evoked significant and congruent changes: (1)
      In the lower limb, transcranial stimulation provided increased heteronymous Ia
      facilitation and decreased D1 inhibition, both of which suggest a decrease in
      presynaptic inhibition of Ia afferents; (2) in the upper limb, transcranial
      stimulation provided an increase in the radial-induced inhibition of the wrist
      flexor H-reflex and a decrease in the peak of monosynaptic Ia excitation in
      single units, both of which suggest an increase in presynaptic inhibition.
      Selectivity of corticospinal effects was explored by testing presynaptic
      inhibition of Ia afferents to soleus motoneurones and focusing the transcranial
      stimulation to excite preferentially different motor nuclei (soleus, quadriceps
      and tibialis anterior). A cortical-induced decrease in presynaptic inhibition of
      Ia afferents was seen when, and only when, cortical and peripheral Ia volleys
      were directed to the same motor nucleus.

PMID- 9588777
TI  - Coordination in prehension. Information-based coupling of reaching and grasping.
AB  - Prehension involves the coordination of a reaching and a grasping movement, such
      that the hand opens and closes in tune with the transport of the hand to the
      object to be grasped. To investigate this coordination, we focused on the
      transition from hand opening to hand closing in the grasping component of
      prehension. Earlier research has suggested that the time taken to close the hand
      remains constant over varying reaching amplitudes. In the present experiment, in
      which subjects reached for objects at six different distances and for objects
      that moved away from them at three different, constant speeds, hand-closure time
      was found to vary as a function of experimental conditions. Moreover, initiation
      of hand closure did not occur at a constant value of the (perceptually available)
      first-order time remaining until contact with the object. However, the variations
      observed, occurring as a function of initial hand-object distance and object
      speed, could be accounted for by an abstract dynamical model of perceptually
      driven postural changes.

PMID- 9588778
TI  - Deficits in vertical and torsional eye movements after uni- and bilateral
      muscimol inactivation of the interstitial nucleus of Cajal of the alert monkey.
AB  - The mesencephalic interstitial nucleus of Cajal (iC) is considered the neural
      integrator for vertical and torsional eye movements and has also been proposed to
      be involved in saccade generation. The aim of this study was to elucidate the
      function of iC in neural integration of different types of eye movements and to
      distinguish eye movement deficits due to iC impairment from that of the
      immediately adjacent rostral interstitial nucleus of the medial longitudinal
      fasciculus (riMLF). We addressed the following questions: (1) According to the
      neural integrator hypothesis, all eye movements including the saccadic system and
      the vestibulo-ocular reflex (VOR) share a common neural integrator. Do iC lesions
      impair gaze-holding function for vertical and torsional eye positions and the
      torsional and vertical VOR gain to a similar degree? (2) What are the dynamic
      properties of vertical and torsional eye movements deficits after iC lesions,
      e.g., the specificity of torsional and vertical nystagmus? (3) Is iC involved in
      saccade generation? We performed 13 uni- and three bilateral iC inactivations by
      muscimol microinjections in four alert monkeys. Three-dimensional eye movements
      were studied under head-stationary conditions during vertical and torsional VOR.
      Under static conditions, unilateral iC injections evoked a shift of Listing's
      plane to the contralesional side (up to 20 degrees), which increased
      (ipsilesional ear down) or decreased (ipsilesional ear up) by additional static
      vestibular stimulation in the roll plane, i.e., ocular counterroll was preserved.
      The monkeys showed a spontaneous torsional nystagmus with a profound downbeat
      component. The fast phases of torsional nystagmus always beat toward the lesion
      side (ipsilesional). Pronounced gaze-holding deficit for torsional and vertical
      eye positions (neural integrator failure) was reflected by the reduction of time
      constants of the exponential decay of the slow phase to 330-370 ms. Whereas the
      vertical oculomotor range was profoundly decreased (up to 50%) and vertical
      saccades were reduced in amplitude, saccade velocity remained normal and
      horizontal eye movements were not affected. Bilateral iC injections reduced the
      shift of Listing's plane caused by unilateral injections, i.e., back toward the
      plane of zero torsion. Torsional nystagmus reversed its direction and ceased,
      whereas vertical nystagmus persisted. In contrast to unilateral injection, there
      was additional upbeating nystagmus. Time constants of the position integrator of
      the gaze-holding system did not differ between unilateral and bilateral
      injections. The range of stable vertical eye positions and saccade amplitude was
      smaller when compared with unilateral injections, but the main sequence remained
      normal. Dynamic vestibular stimulation after unilateral iC injections had
      virtually no effect on torsional and vertical VOR gain and phase at the same time
      when time constants already indicated severe integrator failure. Torsional VOR
      elicited a constant slow-phase velocity offset up to 30 degrees toward the
      contralesional side, i.e., in the opposite direction to spontaneous torsional
      nystagmus. Likewise, vertical VOR showed a velocity offset in an upward
      direction, i.e., opposite to the spontaneous downbeat nystagmus. Contralesional
      torsional and upward vertical quick phases were missing or severely reduced in
      amplitude but showed normal velocity. In contrast, bilateral iC injections
      reduced the gain of the torsional and vertical VOR by 50% and caused a phase lead
      of 10-20 degrees (eye compared with head velocity). We propose that the slow
      phase velocity offset during torsional and vertical VOR reflects a vestibular
      imbalance. It therefore appears likely that the vertical and torsional nystagmus
      after iC lesions is not only caused by a neural integrator failure but also by a
      vestibular imbalance. Unilateral iC injections have clearly differential effects
      on the VOR and the gaze-holding function. (ABSTRACT TRUNCATED)

PMID- 9588779
TI  - Evidence for a photosensitive region in the caudal mesencephalon of the turtle
      brain.
AB  - Using an in vitro brainstem-cerebellum preparation from the turtle Chrysemys
      picta, burst discharge was recorded from the abducens nerve when light was
      directed on the brainstem. This burst discharge likely represents a neural
      correlate of the eye-blink reflex. Increasing the intensity of the light stimulus
      reduced the response latency from a duration of many seconds to approximately 1-2
      s. No response was recorded when the light source was covered. The response was
      present when infrared light was blocked, and it could only be produced when the
      light spectra contained wavelengths below approximately 550 nm. Lesion
      experiments reveal that the photosensitive area is located caudal to the
      trochlear nerve and rostral to the trigeminal nerve. Single-unit microelectrode
      recordings demonstrate that this region is tonically active in the dark and that
      activity is suppressed by light. Pharmacological results show that the light
      response is blocked by application of compounds that act as serotonergic
      antagonists, and that antagonists of noradrenergic receptors (alpha or beta)
      either have no effect or their actions are variable. Taken together, these data
      suggest that an isthmo-optic-like area in the turtle brain is photosensitive to
      direct light and activates neural circuits that control eye movements.

PMID- 9588780
TI  - Spatio-temporal and kinematic analysis of pointing movements performed by
      cerebellar patients with limb ataxia.
AB  - Three patients with cerebellar limb ataxia and three age-matched controls
      performed arm-pointing movements towards a visual stimulus during an experimental
      procedure using a double-step paradigm in a three-dimensional space. Four types
      of trajectories were defined: P1, single-step pointing movement towards the
      visual stimulus in the initial position S1; P2, double-step pointing movement
      towards S1; P3, double-step straight pointing movement towards the second
      position S2; and P4, double-step pointing movement towards S2 with an initial
      direction towards S1. We found that the cerebellar patients, as well as the
      controls, were able to modify their motor programs, but with impaired timing,
      severe anomalies in the direction and amplitude of the changed movement
      trajectories and alteration of the precision of the pointing movements.

PMID- 9588781
TI  - Persistence in visual feedback control by the elderly.
AB  - Young and elderly subjects performed aiming movements to a visual target with a
      manipulandum to determine whether the elderly reduce their reliance on visual
      feedback after extended practice. Reliance on visual feedback was assessed by
      performance on trials in which the cursor displaying arm movement was
      unpredictably extinguished. Movements were divided into two subcomponents: a
      primary, ballistic submovement and a secondary, corrective submovement. For both
      age groups, removal of visual feedback prior to practice resulted in a decrease
      in the distance covered in the primary submovement, an increase in the distance
      of the secondary submovement, and a decrease in endpoint accuracy. After
      extensive practice with the cursor present, the proportion of distance traveled
      with the primary submovement was again assessed under trial conditions in which
      the cursor randomly disappeared. Following practice, the young demonstrated that
      they were capable of extending the primary submovement distance closer to the
      target. In addition, primary submovement distance was unaffected by the removal
      of vision following practice. After practice the elderly did not show evidence of
      lengthening the primary submovement, and submovement distance and endpoint
      accuracy continued to be altered by the removal of vision. This suggests that,
      unlike the young, the elderly do not benefit from practice so that they can place
      a greater proportion of the movement under program control. Thus, on a relative
      basis, a greater proportion of their overall movement requires corrective
      adjustments.

PMID- 9588782
TI  - Registered eye position: short- and long-term effects of botulinum toxin injected
      into eye muscle.
AB  - Botulinum toxin is sometimes injected into human eye muscles as an alternative to
      surgery in the correction of strabismus. Within minutes of botulinum injections
      into ungulate eye muscles, proprioceptive discharge from muscle spindles
      decreases dramatically. It is only over 7-48 h, however, that surgically treated
      strabismus patients usually show an altered proprioceptive signal about eye
      position, presumably from the palisade endings attached to the global multiply
      innervated fibers. How quickly will botulinum toxin alter proprioceptive
      registration of eye position in humans? First, to examine the short-term effects,
      we measured open-loop pointing responses (which requires knowledge of eye
      position) in six strabismus patients preinjection and then over a 45 min
      postinjection period, and in six normal controls over the same time period.
      Second, to examine the long-term effects, 13 strabismus patients were tested
      preinjection and then daily over the next 3 weeks, and three normal controls over
      the same time period. We compared their open-loop pointing responses with the
      injected eye fixating the target to the photographically determined position of
      the occluded other eye (a measure of where the patient would point if eye
      position were determined by efference, not proprioception). There were three
      groups of patients: esotropes with no previous injection, exotropes with no
      previous injection, and exotropes with previous injection. First, all patients
      showed significant correction of their tropias. Second, over the short-term,
      there was no difference in pointing responses found between the patients and the
      controls (t(18) = -1.427, P = 0.1706). Third, over the long-term, however, the
      difference between the pointing responses and eye position information was
      compared among the four groups across four posttests and a significant difference
      found (F3,12 = 58.988, P < 0.00001). Only in patients with no previous injections
      was there altered proprioceptive feedback about eye position. Also, injections
      into the medial rectus induced a significantly greater proprioceptive response
      than those injected into the lateral rectus. In humans, botulinum toxin alters
      proprioception from eye muscles only over the long-term. We suggest that the
      toxin temporarily affects proprioceptive feedback from palisade endings.

PMID- 9588783
TI  - Coordination of multi-joint arm movements in cerebellar ataxia: analysis of hand
      and angular kinematics.
AB  - Kinematic abnormalities of fast multijoint movements in cerebellar ataxia include
      abnormally increased curvature of hand trajectories and an increased hand path
      and are thought to originate from an impairment in generating appropriate levels
      of muscle torques to support normal coordination between shoulder and elbow
      joints. Such a mechanism predicts that kinematic abnormalities are pronounced
      when fast movements are performed and large muscular torques are required.
      Experimental evidence that systematically explores the effects of increasing
      movement velocities on movement kinematics in cerebellar multijoint movements is
      limited and to some extent contradictory. We, therefore, investigated angular and
      hand kinematics of natural multijoint pointing movements in patients with
      cerebellar degenerative disorders and healthy controls. Subjects performed self
      paced vertical pointing movements with their right arms at three different target
      velocities. Limb movements were recorded in three-dimensional space using a two
      camera infrared tracking system. Differences between patients and healthy
      subjects were most prominent when the subjects performed fast movements. Peak
      hand acceleration and deceleration were similar to normals during slow and
      moderate velocity movements but were smaller for fast movements. While altering
      movement velocities had little or no effect on the length of the hand path and
      angular motion of elbow and shoulder joints in normal subjects, the patients
      exhibited overshooting motions (hypermetria) of the hand and at both joints as
      movement velocity increased. Hypermetria at one joint always accompanied
      hypermetria at the neighboring joint. Peak elbow angular deceleration was
      markedly delayed in patients compared with normals. Other temporal movement
      variables such as the relative timing of shoulder and elbow joint motion onsets
      were normal in patients. Kinematic abnormalities of multijoint arm movements in
      cerebellar ataxia include hypermetria at both the elbow and the shoulder joint
      and, as a consequence, irregular and enlarged paths of the hand, and they are
      marked with fast but not with slow movements. Our findings suggest that kinematic
      movement abnormalities that characterize cerebellar limb ataxia are related to an
      impairment in scaling movement variables such as joint acceleration and
      deceleration normally with movement speed. Most likely, increased hand paths and
      decomposition of movement during slow movements, as described earlier, result
      from compensatory mechanisms the patients may employ if maximum movement accuracy
      is required.

PMID- 9588784
TI  - Multijoint arm movements in cerebellar ataxia: abnormal control of movement
      dynamics.
AB  - In cerebellar ataxia, kinematic aberrations of multijoint movements are thought
      to originate from deficiencies in generating muscular torques that are adequate
      to control the mechanical consequences of dynamic interaction forces. At this
      point the exact mechanisms that lead to an abnormal control of interaction
      torques are not known. In principle, the generation of inadequate muscular
      torques may result from an impairment in generating sufficient levels of torques
      or from an inaccurate assessment and prediction of the mechanical consequences of
      movements of one limb segment on adjacent joints. We sought to differentiate the
      relative contribution of these two mechanisms and, therefore, analyzed
      intersegmental dynamics of multijoint pointing movements in healthy subjects and
      in patients with cerebellar degeneration. Unrestrained vertical arm movements
      were performed at three different target movement velocities and recorded using
      an optoelectronic tracking system. An inverse dynamics approach was employed to
      compute net joint torques, muscular torques, dynamic interaction torques and
      gravitational torques acting at the elbow and shoulder joint. In both groups,
      peak dynamic interaction forces and peak muscular forces were largest during fast
      movements. In contrast to normal subjects, patients produced hypermetric
      movements when executing fast movements. Hypermetric movements were associated
      with smaller peak muscular torques and smaller rates of torque change at elbow
      and shoulder joints. The patients' deficit in generating appropriate levels of
      muscular force were prominent during two different phases of the pointing
      movement. Peak muscular forces at the elbow were reduced during the initial phase
      of the movement when simultaneous shoulder joint flexion generated an extensor
      influence upon the elbow joint. When attempting to terminate the movement,
      gravitational and dynamic interaction forces caused overshooting extension at the
      elbow joint. In normal subjects, muscular torque patterns at shoulder and elbow
      joint were synchronized in that peak flexor and extensor muscular torques
      occurred simultaneously at both joints. This temporal pattern of muscular torque
      generation at shoulder and elbow joint was preserved in patients. Our data
      suggest that an impairment in generating sufficient levels of phasic muscular
      torques significantly contributes to the patients' difficulties in controlling
      the mechanical consequences of dynamic interaction forces during multijoint
      movements.

PMID- 9588785
TI  - Vestibular-evoked electromyographic responses in soleus: a comparison between
      click and galvanic stimulation.
AB  - The aim of this study was to demonstrate, if possible, vestibulospinal reflex
      responses in soleus using a stimulus known to be capable of exciting vestibular
      afferents, namely 100-dB (NHL) clicks. We were able to show short-latency
      electromyographic (EMG) responses after clicks in five of eight normal subjects,
      and then we compared these responses with those after transmastoid galvanic
      stimulation (12 normal subjects). Stimulation of the side towards which the head
      was rotated (i.e. the side facing backwards) with either clicks or the cathode
      (anode applied to the opposite side) gave an initial excitatory response in
      soleus, while click or cathodal stimulation of the opposite side (i.e. the side
      facing forwards) gave an initial inhibitory response. Onset latencies and
      modulation with changes in postural task were identical for both click- and
      galvanic-evoked responses. In addition, there was a significant correlation
      between the amplitudes of the responses in soleus after click and galvanic
      stimulation (R2=0.72). These similarities suggest that the earliest reflex
      responses in soleus after clicks and galvanic stimulation may be mediated by a
      common central pathway. In contrast, there was no correlation between the
      amplitudes of responses evoked by 100-dB clicks in soleus and those evoked by the
      same stimulus in the sternocleidomastoid. We conclude that vestibular activation
      by clicks can evoke reflex responses in lower-limb muscles and these responses
      have similar characteristics to the earliest responses evoked by galvanic
      vestibular stimulation.

PMID- 9588786
TI  - Final posture of the upper limb depends on the initial position of the hand
      during prehension movements.
AB  - The question of knowing how the nervous system transforms a desired position and
      orientation of the hand into a set of arm and forearm angles has been widely
      addressed during the last few decades. Despite this fact, it still remains
      unclear as to whether a unique posture of the arm is associated with every
      location and orientation of the hand in space. The main objective of the present
      study a was to address this question. To this end, we studied a prehension task
      requiring human subjects to reach and grasp a cylindrical object presented at
      different locations, along variable orientations. In contrast to previous
      investigations, we considered the influence of the initial position of the hand.
      Results showed that the posture of the arm: (1) varied systematically as a
      function of the movement starting point; (2) was stereotyped for a particular
      subject given a configuration of the object and a movement starting location; (3)
      was altered at both the distal and proximal levels when the orientation of the
      object was changed; (4) was similarly influenced by the experimental factors in
      all the subjects, except one. When considered together, the previous results
      support three main conclusions: First, the nervous system solves the joint
      redundancy problem using fixed strategies. Second, these fixed strategies do not
      provide a single correspondence between hand configuration and arm posture.
      Third, the position and orientation of the hand in space are unlikely to be
      controlled through separate independent neural pathways.

PMID- 9588787
TI  - The effects of cytotoxic entorhinal lesions and electrolytic medial septal
      lesions on the acquisition and retention of a spatial working memory task.
AB  - Rats with lesions either of medial septal nucleus (MSN) or the entorhinal cortex
      (ECx) were compared postoperatively with unoperated controls in a discrete-trial,
      delayed matching-to-position (DMTP) task, conducted on an elevated T-maze. A DMTP
      trial consisted of two consecutive visits to the maze: an information run and a
      choice run. The animals were first forced to visit a randomly selected choice arm
      in the information run. In the choice run, the correct response was to match the
      choice arm that had been visited on the information run, regardless of whether
      the information run itself had been rewarded or not. MSN animals failed to
      succeed in this task, performing at close to chance level throughout training. On
      the other hand, ECx rats consistently perform at a level comparable with that of
      unoperated controls; both groups attained more than 90% correct after 192 trials.
      Long-term retention testing was carried out after an intermission of 4 weeks,
      when the same task was re-administered to the ECx and unoperated control animals.
      ECx animals showed significantly less saving than controls in the retention test.
      In contrast, when the retention interval within a DMTP trial was increased by the
      imposition of a 20-s delay between the information and choice runs, the ECx group
      was not selectively affected by this manipulation.

PMID- 9588788
TI  - The golden age of bacterial genomics.

PMID- 9588789
TI  - Genome encyclopedias and their use for comparative analysis of Rhodobacter
      capsulatus strains.
AB  - This paper consists of two components: the use of gene encyclopedias in genomic
      studies and Rhodobacter capsulatus genome project. A survey of vectors used for
      encyclopedia construction includes a brief discussion of their relative
      advantages and limitations. Projects employing various methods of encyclopedia
      assembly including the comparison of restriction patterns, restriction maps,
      linking by hybridization, oligonucleotide fingerprinting, sequence tagged site
      (STS) fingerprinting and encyclopedias derived from genetic maps are listed and
      briefly described. The R. capsulatus SB 1003 genome project started with the
      construction of its cosmid encyclopedia, which comprises 192 cosmids covering the
      chromosome and the 134 kbp plasmid in strain SB 1003, with the exact map
      coordinates of each cosmid. In a pilot sequencing study, several cosmids were
      individually subcloned using the vector M13mp18 and merged into one 189 kbp
      contig. About 160 open reading frames (ORFs) identified by the CodonUse program
      were subjected to similarity searches. The biological functions of eighty ORFs
      could be assigned reliably using the WIT (what is there) genome investigation
      environment. Eighty percent of these recognizable ORFs were organized in
      functional clusters, which simplified assignment decisions and increased the
      strength of the predictions. A set of 26 genes for cobalamin biosynthesis, genes
      for polyhydroxyalkanoic acid metabolism, DNA replication and recombination, and
      DNA gyrase were among those identified. Recently, another 1.2 Mbp genome fragment
      of the Rhodobacter genome was sequenced using a slightly modified approach. These
      results together with some genome investigation tools, have been placed at our
      web site (http://capsulapedia.uchicago.edu). The sequence of R. capsulatus is
      expected to be completed by summer 1998. A project to construct a systematic set
      of deletion strains of R. capsulatus in order to assign functions to unknown ORFs
      has been started. Preliminary data demonstrate the extreme convenience of the
      unique gene transfer agent (GTA) system to perform such work.

PMID- 9588790
TI  - Selective generation of chromosomal cosmid libraries within the Trypanosoma cruzi
      genome project.
AB  - From a total genomic cosmid library of the pathogen Trypanosoma cruzi, specific
      sublibraries of the smallest four chromosomes were isolated by hybridization of
      the respective chromosomal bands obtained from pulsed-field gels. These libraries
      form the basis for initial mapping analyses that should provide information
      useful for both the ongoing physical mapping of the entire genome and eventual
      sequence analyses. Selectivity of the procedure was high with 75% to 92%,
      although cross-hybridization had to be expected from ubiquitous DNA features,
      such as centromeric and telomeric sequences, and other regions homologous between
      individual chromosomes. Overall, the number of identified clones was slightly
      higher than expected but well within the intrinsic experimental variation
      considering the uncertainty about the exact genome size, the variability in
      clonability and the higher frequency of repeat sequences in larger chromosomes.
      Chromosome III- and IV-specific cosmids were analyzed on Southern blots of
      chromosomal separations. For strain CL Brener, all clones tested exhibited cross
      hybridization to a homologous chromosome larger than 1 Mbp, supporting the
      assumption of the respective chromosome couple being diploid pairs.

PMID- 9588791
TI  - Hybridization mapping of Trypanosoma cruzi chromosomes III and IV.
AB  - As part of the Trypanosoma Genome Initiative launched by the World Health
      Organization (WHO), a physical clone map of Trypanosoma cruzi chromosomes III and
      IV was generated to facilitate both DNA sequence analysis of the parasite's
      genome and the investigation of chromosome organization. Apart from a few genetic
      markers, anonymous cosmids were taken from chromosomal sublibraries and
      individually hybridized to filter arrays of the relevant cosmid library. The
      probe order was determined from the hybridization fingerprint results and used to
      define a fitting clone order, with few gaps remaining. The results were
      independently verified by hybridizations to a bacterial artificial chromosome
      (BAC) library and, in case of chromosome III, restriction mapping. For gap
      closure, additional experiments on a total cosmid library were carried out. The
      possible tiling paths consist of 26 clones for chromosome III (610 kbp) and 28
      clones for chromosome IV (680 kbp).

PMID- 9588792
TI  - Cloning of prokaryotic genomes in yeast artificial chromosomes: application to
      the population genetics of Pseudomonas aeruginosa.
AB  - Yeast artificial chromosomes (YACs) can accommodate large inserts and hence
      should be attractive tools for intra- and interspecies comparisons of bacterial
      genomes. YAC libraries were constructed from size-selected partial digests of
      human and Pseudomonas aeruginosa PAO DNA and SpeI-restricted PAO DNA. Whereas
      YACs from human DNA had an average size of 350 kilobase pairs (kbp), a P.
      aeruginosa sequence larger than 120 kbp was absent or truncated in the eukaryotic
      host. Coligation occurred for YACs smaller than 40 kbp, but stable YACs with 40
      120 kbp large inserts of P. aeruginosa DNA were obtained in high yield. SpeI
      restricted chromosomes from 97 P. aeruginosa strains representing 47 genotypes
      were hybridized with stable YACs from three equidistant regions of the PAO
      genome. The low complexity of hybridizing bands demonstrated that the analyzed
      100 kbp sequence contigs were stably maintained in most P. aeruginosa isolates
      from both disease and environmental habitats.

PMID- 9588793
TI  - Smith/Birnstiel mapping of genome rearrangements in Pseudomonas aeruginosa.
AB  - A novel application of the Smith/Birnstiel technique is presented for the
      analysis of intraspecies genomic diversity in small genomes. Rare-cutter total/N
      frequent-cutter partial restriction digestions are separated in N separate lanes
      by pulsed-field gel electrophoresis, blotted and hybridized with rare-cutter
      fragment ends as probes. The evaluation of the autoradiogram results in high
      resolution restriction maps of 10-200 kbp regions. The technique was applied to
      the analysis of genome rearrangements in Pseudomonas aeruginosa strains.
      Comparison of the region encoding the tryptophan biosynthesis genes in the PAO
      and the IATS serotype 5 strains revealed that shared sequence characterized by
      almost identical restriction fingerprints was interrupted in the serotype 5
      strain by small islands displaying strain-specific restriction site signatures. A
      multistep rearrangement in a hypervariable chromosome region downstream of the
      phn locus was detected in serial airway isolates from a patient with cystic
      fibrosis.

PMID- 9588794
TI  - High-throughput robotic system for sequencing of microbial genomes.
AB  - A high-throughput robotic workstation system was used for double-stranded plasmid
      DNA template preparation and sequencing reaction setup to streamline the
      sequencing process in genome projects. All 96-well miniprep kits that were tested
      provided high quality plasmid DNA suitable for fluorescent DNA sequencing. After
      quantitation in a 96-well UV spectrophotometer, the plasmid DNA was used as
      template to automatically set up sequencing reactions. The setup was controlled
      by spread sheets that were imported into the robotic system. We utilized this
      integrated system to prepare all necessary shotgun templates for our
      contributions to a number of large-scale genome projects as well as a full-length
      cDNA sequencing project.

PMID- 9588795
TI  - Optimization and automation of fluorescence-based DNA hybridization for high
      throughput clone mapping.
AB  - Large-scale hybridization-based genome mapping projects, such as the production
      of sequence-ready physical clone maps, call for robust and cheap DNA labeling
      techniques that are amenable to automation. We routinely use a high-throughput
      protocol based on fluorescence detection. DNA probes are labeled via polymerase
      chain reaction (PCR) amplification with primers that are digoxigenin-modified at
      their 5' ends. Alternatively, digoxigenin-labeled dUTP is incorporated in a
      random hexamer priming reaction. Hybridization takes place in small volumes by
      sandwiching the probe between filters and plastic sheets. A fluorescence signal
      is produced by the activity of alkaline phosphatase attached to an anti
      digoxigenin antibody upon the addition of AttoPhos substrate. Signals are
      directly detected with a charge-coupled device (CCD) camera and scored by an
      image data analysis system. DNA filters can be reused at least 40 times without
      loss of data quality. Significant advantages compared to radioactive techniques
      are the reduced health risk, enabling highly parallel processing; the production
      of spot signals uniform in size and intensity, which is essential for efficient
      image analysis; and a cost reduction of about 70%.

PMID- 9588796
TI  - Differential genome analysis of bacteria by genomic subtractive hybridization and
      pulsed field gel electrophoresis.
AB  - A comprehensive analysis of the differences between the genomes of two closely
      related bacterial strains should give insight into the molecular basis of their
      individual phenotypic and genotypic characteristics. Here we present an
      integrative approach including two different strategies for the thorough
      investigation of genomic divergence. We have combined two techniques including
      genomic subtractive hybridization and comparative genome mapping by pulsed field
      gel electrophoresis (PFGE) techniques. The subtractive method for which a
      protocol is given herein results in the production of a library of specific DNA
      sequence tags present only in one strain, while the construction of
      macrorestriction maps of the bacterial chromosomes yields data about the overall
      genome organization and the arrangement and distance of gene loci. Comparison of
      the physical and genetic maps and determination of the map positions of the
      strain-specific DNA sequences reveals gross chromosomal modifications, insertions
      or deletions of additional genetic material, and transpositional events. The
      further investigation of the strain-specific regions yields information about the
      nature and origin of the acquired DNA and their influence on the evolution of the
      individual bacterial genome. The two methods were applied to differential genome
      analysis of clonal divergence in Pseudomonas aeruginosa choosing two clone C
      isolates from diverse habitats.

PMID- 9588797
TI  - Global analysis of genomic texts: the distribution of AGCT tetranucleotides in
      the Escherichia coli and Bacillus subtilis genomes predicts translational
      frameshifting and ribosomal hopping in several genes.
AB  - Present availability of the genomic text of bacteria allows assignment of
      biological known functions to many genes (typically, half of the genome's gene
      content). It is now time to try and predict new unexpected functions, using
      inductive procedures that allow correlating the content of the genomic text to
      possible biological functions. We show here that analysis of the genomes of
      Escherichia coli and Bacillus subtilis for the distribution of AGCT motifs
      predicts that genes exist for which the mRNA molecule can be translated as
      several different proteins synthesized after ribosomal frameshifting or hopping.
      Among these genes we found that several coded for the same function in E. coli
      and B. subtilis. We analyzed in depth the situation of the infB gene
      (experimentally known to specify synthesis of several proteins differing in their
      translation starts), the aceF/pdhC gene, the eno gene, and the rplI gene. In
      addition, genes specific to E. coli were also studied: ompA, ompFand tolA
      (predicting epigenetic variation that could help escape infection by phages or
      colicins).

PMID- 9588799
TI  - Low molecular weight proteins: a challenge for post-genomic research.
AB  - The EcoGene project involves the examination of Escherichia coli K-12 DNA
      sequences and accompanying annotation in the public databases in order to refine
      the representation and prediction of the entire set of E. coli K-12 chromosomally
      encoded protein sequences. The results of this ongoing effort have been deposited
      in the SWISSPROT protein sequence database as sequencing of the E. coli genome
      has progressed to completion in recent years. Through this continuing research,
      we have discovered that the prediction of low molecular weight (small) proteins,
      arbitrarily defined as protein sequences < or = 150 amino acids (aa) in length,
      is problematic and requires special attention. We describe the small protein
      subset of EcoGene and the approach used to derive this subset from the complete
      E. coli genome sequence and database annotations. These E. coli proteins have
      helped to identify new small genes in other organisms and to identify conserved
      residues (motifs) using database searches and multiple alignments. Two thirds of
      the E. coli small proteins have not been characterized experimentally. The
      careful application of computer and laboratory methods to the analysis of small
      proteins is needed for accurate prediction, verification and characterization.
      The problem of accurate protein sequence identification is not limited to small
      proteins or to E. coli; these problems are encountered to varying degrees
      throughout all sequence databases.

PMID- 9588798
TI  - Tetranucleotide frequencies in microbial genomes.
AB  - A computational strategy for determining the variability of long DNA sequences in
      microbial genomes is described. Composite portraits of bacterial genomes were
      obtained by computing tetranucleotide frequencies of sections of genomic DNA,
      converting the frequencies to color images and arranging the images according to
      their genetic position. The resulting images revealed that the tetranucleotide
      frequencies of genomic DNA sequences are highly conserved. Sections that were
      visibly different from those of the rest of the genome contained ribosomal RNA,
      bacteriophage, or undefined coding regions and had corresponding differences in
      the variances of tetranucleotide frequencies and GC content. Comparison of nine
      completely sequenced bacterial genomes showed that there was a nonlinear
      relationship between variances of the tetranucleotide frequencies and GC content,
      with the highest variances occurring in DNA sequences with low GC contents (less
      than 0.30 mol). High variances were also observed in DNA sequences having high GC
      contents (greater than 0.60 mol), but to a much lesser extent than DNA sequences
      having low GC contents. Differences in the tetranucleotide frequencies may be due
      to the mechanisms of intercellular genetic exchange and/or processes involved in
      maintaining intracellular genetic stability. Identification of sections that were
      different from those of the rest of the genome may provide information on the
      evolution and plasticity of bacterial genomes.

PMID- 9588800
TI  - Structural and functional implications of sequence diversity of Pseudomonas
      aeruginosa genes oriC, ampC and fliC.
AB  - Sequence analysis of three representative gene loci, oriC, ampC and fliC, in 19
      Pseudomonas aeruginosa strains revealed a low sequence diversity that does not
      correlate with the extensive diversity of P. aeruginosa habitats. Single point
      mutations lead to a mean sequence diversity of 0.40%, 0.38% and 0.59% for oriC,
      ampC and a-type fliC, respectively, but of only 0.05% for b-type flagellin genes.
      The analyzed genes encode highly conserved functions that are subject to strong
      selective pressure. The detected nucleotide substitutions of oriC, accumulating
      in a central 95 bp region, affect neither the putative DnaA binding sites nor the
      13 bp direct repeats that presumably provide the sites to open oriC duplex DNA.
      Even in P. aeruginosa strain DSM 1128, which exhibits an unusually high sequence
      variability in several analyzed genes, the 9 bp and 13 bp motifs are conserved,
      reflecting their essential functional role in replication initiation. The two
      flagellin types, differing by 37-38% in their primary structure, exhibit
      pronounced structural and functional homology, as shown by alignment of flagellin
      variants by hydrophobicity index, probability of surface exposure, chain
      flexibility and antigenicity, and by cross-reactivity between both proteins using
      specific antisera. Five nonsynonymous nucleotide substitutions of ampC lead to
      beta-lactamase variants that differ in recognition and turnover of substrate, as
      deduced from the three-dimensional structure of the highly homologous
      Enterobacter cloacae beta-lactamase and confirmed by inhibition kinetics. The
      identified point mutations in the three genes are classified as selectively
      equivalent sequence variants indicating neutral genetic drift as a mechanism of
      molecular evolution in P. aeruginosa, rather than positive selection.

PMID- 9588801
TI  - Illuminating the agent of syphilis: the Treponema pallidum genome project.
AB  - As the causative agent of the common sexually transmitted disease syphilis and a
      fastidious, microaerophilic obligate parasite of humans, Treponema pallidum
      subsp. pallidum is one of the few prominent infectious agents that has not been
      cultured continuously in vitro. T pallidum therefore represents an attractive
      candidate for genomic sequencing. Preliminary sequence results from the 1.13
      million base pair genome are consistent with the expected limited metabolic
      capabilities of this spirochete, but indicate that the bacterium may express
      toxins and surface proteins that have not been identified previously.

PMID- 9588802
TI  - Bacterial phylogeny based on comparative sequence analysis.
AB  - Comparative sequence analysis of small subunit rRNA is currently one of the most
      important methods for the elucidation of bacterial phylogeny as well as bacterial
      identification. Phylogenetic investigations targeting alternative phylogenetic
      markers such as large subunit rRNA, elongation factors, and ATPases have shown
      that 16S rRNA-based trees reflect the history of the corresponding organisms
      globally. However, in comparison with three to four billion years of evolution
      the phylogenetic information content of these markers is limited. Consequently,
      the limited resolution power of the marker molecules allows only a spot check of
      the evolutionary history of microorganisms. This is often indicated by locally
      different topologies of trees based on different markers, data sets or the
      application of different treeing approaches. Sequence peculiarities as well as
      methods and parameters for data analysis were studied with respect to their
      effects on the results of phylogenetic investigations. It is shown that only
      careful data analysis starting with a proper alignment, followed by the analysis
      of positional variability, rates and character of change, testing various data
      selections, applying alternative treeing methods and, finally, performing
      confidence tests, allows reasonable utilization of the limited phylogenetic
      information.

PMID- 9588804
TI  - Mycobacterial genome structure.
AB  - Genome maps have been constructed for the mycobacterial pathogens Mycobacterium
      leprae and Mycobacterium tuberculosis, as well as for the attenuated vaccine
      strain Mycobacterium bovis BCG Pasteur. While the chromosomes of M. tuberculosis
      and M. bovis BCG Pasteur show extensive conservation at the gross level,
      comparison with M. leprae revealed a high degree of diversification, with a
      mosaic-like pattern apparent. The ordered libraries of M. tuberculosis and M.
      leprae produced during the course of these studies played a central role in the
      genome sequencing projects of these two bacilli, showing the utility of this
      approach for systematic sequencing of bacterial genomes.

PMID- 9588803
TI  - Chromosomal rearrangements in enteric bacteria.
AB  - Early genetic studies showed conservation of gene order in the enteric bacteria.
      Two recent methods using pulsed field gel electrophoresis (PFGE) to determine the
      physical map of the genome are: (i) partial digestion with the endonuclease I
      CeuI, which digests the DNA of bacteria in the rrn operon for rRNA (ribosomal
      RNA), thus establishing the "rrn genomic skeleton" (the size in kbp of the
      intervals between rRNA operons); (ii) analysis of XbaI and B1nI sites within Tn10
      insertions in the chromosome. The order of I-CeuI fragments, which is ABCDEFG in
      S. typhimurium LT2 and E. coli K-12, was found to be conserved in most Salmonella
      species, most of which grow in many hosts (host-generalists). However, in S.
      typhi, S. paratyphi C, S. gallinarum, and S. pullorum, species which are host
      specialized, these fragments are rearranged, due to homologous recombination
      between the rrn operons, resulting in translocations and inversions. Inversions
      and translocations not involving the rrn operons are seldom detected except for
      inversions over the TER (termination of replication) region. Additive genetic
      changes (due to lateral transfer resulting in insertion of nonhomologous DNA)
      have resulted in "loops" containing blocks of DNA which provide new genes to
      specific strains, thus driving rapid evolution of new traits.

PMID- 9588805
TI  - Comparison of the genome organization of pathogenic neisseriae.
AB  - Current efforts to completely sequence the meningococcal and gonocococcal genomes
      raise the question whether the lessons learned from the sequenced strains may be
      safely extrapolated to other members of these species, or whether, in view of the
      fact that Neisseriae are highly recombinogenic and exhibit a high degree of
      horizontal intra- and interspecies genetic transfer, only clone-specific
      conclusions are valid. From the known physical and genetic maps of each of two
      gonococcal and meningococcal strains, it would appear that both species exhibit a
      species-specific conservation in their genetic organization while the
      interspecies comparison revealed several rearrangements, although still with a
      high overall similarity. However, these data contrast with other evidence
      suggesting intra-species rearrangements, such as the nonconserved I-CeuI
      macrorestriction patterns of different meningococcal and other neisserial
      strains. Since I-CeuI cuts within the 23S-rRNA sequence, the restriction pattern
      should give reliable information on the distribution of rrn loci in the
      neisserial genomes. Further studies are warranted to answer these questions.

PMID- 9588806
TI  - Chromosome geometry and intraspecific genetic polymorphism in Gram-positive
      bacteria revealed by pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) proved to be a powerful approach to study
      bacterial genomics. The genome structure and genetic polymorphism of Gram
      positive bacteria from the high G+C (Streptomyces) and low G+C (Streptococcus)
      groups have been studied. PFGE allowed the estimation of the size of their genome
      at about 8 Mbp and 1.8 Mbp, respectively, and to get an insight into their
      chromosome geometry. Thus, physical mapping of the genome of wild-type
      Streptomyces ambofaciens strains revealed the linearity of the 8 Mbp chromosomal
      DNA and its typical invertron structure, while the 1.8 Mbp chromosome of
      Streptococcus thermophilus was shown to be circular. These findings disproved the
      long-standing idea of universality of bacterial chromosome circularity. In
      addition, strains belonging to the species S. ambofaciens and S. thermophilus
      allowed us to characterize the genetic polymorphism at the intraspecific level.
      Within the S. thermophilus species, comparison of the physical maps showed a
      relative conservation of gene order as well as restriction sites along the
      chromosome. In contrast, variable loci were characterized that revealed localized
      genome rearrangements. The most spectacular of these corresponded to horizontal
      gene transfer events of sequences. In S. ambofaciens, the physical maps of three
      isolates pointed to the conservation of the genetic organization. However, a
      strong polymorphism was observed in the terminal regions of the linear
      chromosomal DNA. Previous PFGE studies in S. ambofaciens gave proof of a high
      structural instability of a limited region of the chromosome called unstable
      region (i.e., DNA rearrangements such as deletions and amplifications). These
      intraclonal rearrangements create an impressive intraspecific polymorphism of
      genome size and shape (linear or circular). In both organisms, the DNA
      rearrangements are restricted to particular regions of the chromosome.

PMID- 9588808
TI  - Microevolution during epidemic spread of Neisseria meningitidis.
AB  - Similar to many other naturally transformable bacteria, Neisseria meningitidis
      has yielded many examples where horizontal genetic exchange has resulted in
      genetic variation of individual strains. Epidemic strains are purified of genetic
      variants due to bottlenecks during the spread from country to country, resulting
      in clonal descent. Occasionally, clonal replacement also occurs during epidemic
      spread. These processes occur rapidly in serogroup A meningococci; such that
      after their descent from a common ancestor, clonally related bacteria have
      diversified at numerous loci within the last decades.

PMID- 9588807
TI  - Leptospira genomics.
AB  - The bacterial species Leptospira interrogans (sensu stricto) has a complex genome
      containing two circular chromosomal replicons. Comparative analysis of the larger
      chromosome reveals a fluid genetic organization with many large rearrangements
      differentiating two closely related strains. In the present study new genes were
      identified by partial sequence analysis of randomly cloned fragments of L.
      interrogans DNA. These genes were localized in regions of the genome by nucleic
      acid hybridization with DNA fragments separated by pulsed-field gel
      electrophoresis. The resulting genetic maps provide improved resolution for each
      strain and provide evidence for additional chromosomal rearrangements. Insertion
      elements may be involved in recombination events, as several are near regions of
      the chromosome that have undergone rearrangement.

PMID- 9588809
TI  - Mosaic genes and their role in penicillin-resistant Streptococcus pneumoniae.
AB  - Penicillin resistance in clinical isolates of Streptococcus pneumoniae is
      mediated by mosaic genes encoding altered penicillin binding proteins. Mosaic
      sequence blocks are the result of a genetic exchange between related
      streptococcal species. It is likely that resistance has emerged in commensal
      streptococci before being transferred into the pneumococcus. Closely related
      mosaic genes are found in different pneumococcal clones and in different
      streptococcal species isolated worldwide since the first reports on such strains
      in the late 70s, demonstrating the importance of commensal streptococci for the
      spread of selectable markers in naturally transforming pathogens.

PMID- 9588810
TI  - Polymerase chain reaction-mediated typing of microorganisms: tracking
      dissemination of genes and genomes.
AB  - The polymerase chain reaction (PCR) is a powerful molecular biology tool which
      can be used for the identification of species and strains of diverse
      microorganisms. By aimed amplification of characteristic genes (i.e., genes
      encoding ribosomal RNA molecules) and subsequent genetic analysis of amplified
      fragments, information on microbiological systematics and phylogeny can be
      obtained in a fast and efficient manner. Similar types of gene identification can
      be used to verify or detect genes responsible for phenotypic characteristics,
      whereas modified forms of the PCR enable whole genome searches for genetic
      polymorphisms among strains of a given species. In medical sciences, both
      strategies, gene and genome variability analysis by PCR, have an increasing
      impact on the study of the spread of especially those microbes that are multiply
      resistant to clinically used antibiotics. In this communication we will exemplify
      the usefulness of PCR-mediated typing of microorganisms from a clinical
      perspective while focusing on gene- versus genome-scanning. Special emphasis will
      be placed on analysis of the dissemination and characteristics of methicillin
      resistant Staphylococcus aureus (MRSA) strains and bacterial factors providing
      resistance to penicillin and other beta-lactam antibiotics. Technical limitations
      and possibilities for improvement will be discussed.

PMID- 9588811
TI  - Whole genome scan for habitat-specific genes by signature-tagged mutagenesis.
AB  - Large numbers of new open reading frames can be identified by whole genome
      sequencing of microbial genomes. Efficient new approaches are required to
      investigate the role of the putative genes, or to identify genes required in
      distinct habitats. The novel technique 'signature-tagged mutagenesis' allows the
      identification of individual mutants within complex pools of mutants. Large
      numbers of mutants can be analyzed in a parallel manner for negative phenotypes
      like loss of function or attenuation of virulence. Further analysis of mutations
      identified by a negative selection procedure can be performed by linking the
      position of the respective mutations to genes identified by whole genome
      sequencing of microbes.

PMID- 9588812
TI  - Differential display approach to quantitation of environmental stimuli on
      bacterial gene expression.
AB  - The differential display of the mRNA technique for eukaryotes is fruitful in
      identifying genes with altered transcription rates caused by exogenous or
      endogenous stimuli. Prokaryotic analogues of the method using arbitrary
      oligonucleotides may reach a complete statistical genome coverage. Thus a genome
      wide mass screening for transcriptionally regulated sequences will be possible.
      However, the primer sets have to be optimized for a given species to result in
      maximum band yields. Hence the construction of primers requires the calculation
      of oligonucleotide frequency distributions from known coding regions to choose
      sequences with frequent occurrence in the bacterial genome. After completion of
      many whole genome sequencing projects, differentially regulated cDNA sequences
      are readily identified by sequence comparisons.

PMID- 9588813
TI  - European Functional Analysis Network (EUROFAN) and the functional analysis of the
      Saccharomyces cerevisiae genome.
AB  - Less than two yeras after the sequence of its genome was completed, the baker's
      yeast, Saccharomyces cerevisiae, is a leading organism in the rapidly growing
      field of functional genomics. Two thousands novel protein coding genes, nearly
      all of them "orphans", have already been disrupted by the coordinated efforts of
      a large consortium of European laboratories, EUROFAN, and other initiatives. The
      mutants are submitted to many specialized functional assays, and studies are
      performed in parallel at the transcriptome and the proteome levels. With a
      central repository of mutant yeast strains, and a centralized database, EUROFAN
      lays the foundations for the future of genomics with yeast serving both as a
      model and a tool.

PMID- 9588814
TI  - Fragments of amyloid beta induce apoptosis in vascular endothelial cells.
AB  - Injury to cells that was triggered by fragments of amyloid beta protein (A beta)
      was studied in human vascular endothelial cells. A fragment of A beta containing
      amino acids 25-35 promoted cell death, but fragments of A beta containing amino
      acids 31-35 and 35-25 did not have such an effect. The fragment of A beta
      containing amino acids 25-35 induced cell death that was characterized as
      programmed cell death (apoptosis) in view of the accompanying morphological
      changes, the fragmentation of DNA, and the requirement for protein synthesis.

PMID- 9588815
TI  - Suppression of apoptosis by inhibition of phosphatidylcholine-specific
      phospholipase C in vascular endothelial cells.
AB  - In order to clarify the role of phosphatidylcholine-specific phospholipase C (PC
      PLC) in the regulation of apoptosis in vascular endothelial cells (VEC), we
      investigated the effects of D609, a specific inhibitor of PC-PLC, on apoptosis
      that was induced by deprivation of fibroblast growth factor (FGF) and serum and
      also by rattlesnake venom. The early morphological changes (detachment of cells
      from dishes) and the fragmentation of DNA, which is a specific feature of
      apoptotic cell death, were clearly inhibited by D609 in these two apoptosis
      inducing systems. Moreover, the production of diacylglycerol (DAG), which was
      stimulated in apoptotic VEC, was suppressed by D609. The effects of D609 on the
      activity of PC-PLC and on apoptosis of VEC were dose-dependent. Our results
      indicate that PC-PLC is involved in the apoptosis-inducing signal pathway in VEC
      and, that DAG, produced from phosphatidylcholine (PC), might be an important
      mediator in this signal-transduction pathway. Our results also suggest that
      rattlesnake venom, a strong promoter of apoptosis in VEC, might induce apoptosis
      by stimulating PC-PLC and, furthermore, that PC-PLC might play a significant role
      in anchorage-dependent signal transduction in VEC.

PMID- 9588816
TI  - Increase in TUNEL positive cells in aorta from diabetic rats.
AB  - TUNEL staining, which allows detection of fragmented DNA in situ, is commonly
      used as an indication of apoptosis. Recent studies suggest that apoptosis is
      increased in several pathophysiological conditions. In this study we examined the
      hypothesis that chronic diabetes is associated with an increase in TUNEL staining
      of the aorta. Diabetic rats were studied 4-5 months after injection of
      streptozotocin (50 mg/kg). Aorta of diabetic and control rats were examined for
      TUNEL staining, morphology by electron microscopy, and DNA contamination in RNA
      preparation by polymerase chain reaction (PCR). TUNEL staining of aortic sections
      showed a 6 fold increase of positive cells in the media of diabetic aorta (22 +/-
      6%) (mean +/- SE) compared with aorta from age-matched controls (3.6 +/- 0.9%, p
      < 0.05). Electron microscopy demonstrated typical apoptotic cells and bodies in
      the media of aorta from diabetic but not control rats. DNA contamination was
      found in RNA prepared from diabetic aorta, which was detected using PCR, which is
      consistent with increased DNA fragmentation. Increased TUNEL staining was not
      observed in rats with hyperglycemia 3 days after injection of streptozotocin. In
      conclusion, severe chronic diabetes is associated with an increase in TUNEL
      staining, and perhaps apoptosis, in the aorta. We speculate that increased
      apoptosis may compensate for increased proliferative activity in diabetic blood
      vessels.

PMID- 9588817
TI  - Induction of endothelial cell injury by cigarette smoke.
AB  - Cigarette smoke contains different populations of free radicals which may be
      responsible for endothelial cell (EC) injury of smokers. The purpose of this
      study was to examine the effects of gas-phase cigarette smoke on EC endothelium
      derived relaxing factor (EDRF)/NO-guanylate cyclase (GC)-cGMP pathway and on EC
      detachment-type injury after incubation with smoke. Furthermore, we examined
      whether different kind of antioxidants can prevent smoke-caused EC injury. We
      measured cGMP pathway using direct (sodium nitroprusside, SNP) and indirect
      (A23187, the calcium ionophore and bradykinin, BK) activators of GC. Directly and
      indirectly stimulated EC cGMP production dose-dependently decreased and EC
      detachment increased after incubation with smoke. Externally added thiols
      (glutathione, GSH; D-Penicillamine, DP; N-acetylcysteine, NAC) protected EC from
      damage of cGMP production and cell detachment. Other antioxidants (catalase,
      deferoxamine and superoxide dismutase) were ineffective. These results suggest
      that the thiol containing GC in EC is destroyed or inactivated or thiol like
      species responsible for activation of GC is incomplete in EC after incubation
      with smoke. It is also possible that externally added thiols bind an unknown
      component of smoke and this way, EC is protected. EC injury may contribute to
      vascular diseases associated with cigarette smoking.

PMID- 9588818
TI  - Effects of sulphydryl- and non-sulphydryl-containing ACE inhibitors on left
      ventricular relaxation in the isolated guinea pig heart.
AB  - ACE inhibitors exert both acute and chronic beneficial effects on cardiac
      function (e.g remodelling, diastolic dysfunction). We have previously reported
      that the ACE inhibitor captopril induces selective left ventricular (LV) relaxant
      effects in the isolated ejecting guinea pig heart. The aim of the present study
      was to further investigate the mechanism of the captopril-induced changes in
      early LV relaxation by comparing the effects of two sulphydryl and two non
      sulphydryl containing ACE inhibitors in the same experimental preparation.
      Isolated ejecting guinea pig hearts were studied under conditions of constant
      loading and heart rate. LV pressure was monitored by a 2F micromanometer-tipped
      catheter transducer inserted in the LV cavity. The sulphydryl-containing ACE
      inhibitors captopril and zofenaprilat enhanced early LV relaxation, whereas the
      non-sulphydryl-containing ACE inhibitors lisinopril and quinaprilat did not. The
      effects of captopril and zofenaprilat were attenuated both by the nitric oxide
      scavenger haemoglobin and the bradykinin B2-kinin receptor antagonist HOE 140.
      Neither the oxygen free-radical scavenger superoxide dismutase nor the sulphydryl
      containing compound N-acetyl cysteine administered together with lisinopril had
      any effect on LV relaxation. These data demonstrate that inhibition of intra
      cardiac ACE activity may acutely modulate LV relaxation through increased
      activity of the bradykinin-nitric oxide pathway. The presence of a sulphydryl
      group on the relevant ACE inhibitor appears to be essential for this LV relaxant
      effect.

PMID- 9588819
TI  - P2Y- and P2U-mediated increases in internal calcium in single bovine aortic
      endothelial cells in primary culture.
AB  - Increases in intracellular calcium ([Ca2+]i) to ATP, ADP, AMP, adenosine, UTP, 2
      methylthio ATP (2-MeSATP), 2-methylthio ADP (2-MeSADP) and alpha,beta-methylene
      ATP (alpha,beta-meATP) were investigated in single bovine aortic endothelial
      cells (BAEC) in primary culture using Indo-1. Evidence was obtained for the
      presence of P2Y and P2U, but not P2X receptors. Normalized concentration-effect
      curves for ATP, UTP and 2-MeSATP were biphasic in shape. At 10 nM, the agonist
      rank order was UTP > ATP approximately 2-MeSATP, while above 1 microM, it was ATP
      > or = UTP > or = 2-MeSATP. No cross-desensitization between responses to P2U and
      P2Y receptors was observed in normal external solution. However, when internal
      Ca2+ stores were depleted by exposure to 2-MeSATP or UTP in Ca2+-free solution
      and agonists then re-applied in presence of external Ca2+, homologous but not
      heterologous desensitization was seen. In the same conditions, heterologous
      desensitization was observed for UTP after ATP but not for ATP after UTP. Taken
      together, the results are consistent with the coexistence of P2Y and P2U
      receptors in primary-cultured BAEC and suggest that upon activation, different
      intracellular signaling pathways could be involved in increasing [Ca2+]i.

PMID- 9588820
TI  - The endothelium-dependent, substance P relaxation of porcine coronary arteries
      resistant to nitric oxide synthesis inhibition is partially mediated by 4
      aminopyridine-sensitive voltage-dependent K+ channels.
AB  - We examined the role of K+ channels in the endothelium-dependent relaxation which
      is resistant to nitric oxide (NO) synthase inhibition in porcine coronary artery.
      In the presence of 0.2 mM NG-nitro-L-arginine (L-NNA), a potent inhibitor of NO
      synthase, 10 nM substance P (SP) added to 9,11-dideoxy-11alpha,9alpha
      epoxymethano-prostaglandin F2alpha (U46619) contractures elicited a relaxation.
      The L-NNA-resistant relaxation induced by SP was strongly inhibited by 5 mM
      tetrabutylammonium chloride (TBA), a non-specific inhibitor of K+ channels.
      Interestingly, 4-aminopyridine (4-AP, 1 mM), a relatively specific inhibitor of
      voltage-sensitive K+ channels, shortened the duration of SP response, but it had
      no effect on the peak of SP response. Although 4-AP has also been shown to
      inhibit Ca2+-activated K+ channels, the shortening effect of 4-AP in SP response
      was observed in the presence of 1 microM apamin, an inhibitor of small
      conductance Ca2+-activated K+ channels, or 100 nM charybdotoxin, and inhibitor of
      large conductance Ca2+-activated K+ channels. Moreover, although SP stimulates
      both L-NNA-resistant relaxation and endothelium-derived NO-dependent relaxation
      (EDNO) in porcine coronary arteries, a low concentration of 4-AP (1 mM) affected
      only the L-NNA-resistant response, but not the EDNO response. These are the first
      results to show that the L-NNA-resistant relaxation induced by SP, probably,
      endothelium-derived hyperpolarizing factor(s) (EDHF) response, is dependent on
      voltage-dependent K+ channels in porcine coronary artery.

PMID- 9588821
TI  - Relationships between phosphatidylcholine-specific phospholipase C and integrins
      in cell-substratum adhesion and apoptosis in vascular endothelial cells.
AB  - In order to understand the mechanism by which VEC control cell-substratum
      adhesion and apoptosis, we investigated relationships between PC-PLC and the
      integrins that are normally expressed in VEC. We found that promotion of cell
      substratum adhesion by suppression of PC-PLC was almost completely blocked by a
      monoclonal antibody (mAb) against integrin beta1, and was partially blocked by a
      mAb against intergrin beta3. The production of diacylglycerol (DAG) which was
      inhibited by suppression of PC-PLC activity, was increased by mAbs against
      intergrin beta1 and beta3. When the mAb against integrin beta4 was added to the
      seeding medium, cell-substratum adhesion and spreading of cells were triggered,
      but the activity of PC-PLC was unaffected by this mAb. Furthermore, when both the
      mAb against integrin beta4 and a specific inhibitor (D609) of PC-PLC were present
      in the seeding medium, cell-substratum adhesion and spreading were promoted to a
      greater extent than when either of these agents was present alone. These data
      suggest that integrins beta1 and beta3 might regulate cell-substratum adhesion
      and apoptosis via a PC-PLC-dependent pathway, while integrin beta4 might regulate
      these phenomena via PC-PLC-independent pathway. These findings provide the first
      evidence of relationships between PC-PLC and integrins in cell-substratum
      adhesion and apoptosis.

PMID- 9588822
TI  - Heart EC respond heterogeneous on cytokine stimulation in ICAM-1 and VCAM-1, but
      not in MHC expression. A study with 3 rat heart endothelial cell (RHEC) lines.
AB  - Cytokine-induced expression of ICAM-1, VCAM-1, and MHC class I and II was studied
      at different time points in microvascular endothelial cells (EC) of heart origin,
      using three different rat endothelial cell (RHEC) lines that were stimulated with
      TNFalpha and/or IFNgamma. Each of the three RHEC lines responded to TNFalpha as
      well as to IFNgamma; stimulation with combined cytokines led to increased or even
      synergistic effects. TNFalpha was most potent in inducing ICAM-1 and VCAM-1,
      whereas MHC class II was most effectively induced by IFNgamma. The 3 RHEC lines
      responded similarly regarding induction of MHC class II and upregulation of
      constitutively expressed MHC class I on the cells. However, the RHEC lines showed
      remarkable differences with respect to ICAM-1 and VCAM-1 induction, with each
      line having a unique expression profile. In RHEC-3, both ICAM-1 and VCAM-1 were
      well inducible, whereas in RHEC-10, no ICAM-1 and only some VCAM-1 could be
      induced. RHEC-11 showed minimal induction of ICAM-1, but strong induction of VCAM
      1. For P-selectin induction, no such differences were found between the RHEC
      lines. These heterogeneous effects of cytokine stimulation could neither be
      explained by differences in mobilization of calcium nor by ultra-structural
      differences between the lines. Stimulation of the RHEC lines for ICAM-1 and VCAM
      1 or MHC class II molecule induction resulted in expressing and non-expressing
      EC. Experiments with selected and subsequently cultured expressing and non
      expressing cell populations for either ICAM-1, VCAM-1 or MHC class II, indicated
      that this selective induction most likely results from intrinsic regulation
      mechanisms in the cell cultures, and not from the presence of particular EC
      subpopulations within the lines. We conclude that microvascular heart endothelial
      cells, as represented by the 3 RHEC lines, demonstrate a selective heterogeneity
      in expression of ICAM-1 and VCAM-1, but not of MHC class I and II, upon cytokine
      stimulation. The consequences of this heterogeneity for leukocyte-endothelial
      cell interactions in heart inflammation and immune reactivity is discussed.

PMID- 9588823
TI  - Resting distribution and stimulated translocation of protein kinase C isoforms
      alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial
      cells.
AB  - Protein kinase C (PKC) has been linked to functional and morphological changes in
      endothelial cells involved in increased microvessel permeability. Bradykinin and
      TNF are potent inflammatory mediators which translocate PKC from the cytosol to
      the membrane of various cell types, including endothelial cells. The PKC isoforms
      alpha, epsilon and zeta have been demonstrated as the most prominent in human
      umbilical vein endothelial cells (HUVEC). We propose that bradykinin and TNF
      cause increased microvascular permeability via a PKC-dependent endothelial cell
      signalling pathway. HUVEC were incubated at 37 degrees C and 5% CO2 for 1 min, 15
      min and 3 h with either bradykinin (1 microM) or TNF (100 U/ml). PMA incubation
      served as a positive control (100 nM, 15 min). Cytosolic and membrane-bound
      extracts were obtained by incubation in digitonin (0.5%) and Triton X100 (1%).
      PKC isoforms were assayed by Western blot and membrane fractions calculated.
      These experiments revealed that: HUVEC clearly displayed a non-uniform basal
      membrane fraction distribution of PKC isoforms, with zeta (35.4%) greater than
      epsilon (30.6%) and both much greater than alpha (8.6%); Bradykinin caused
      significant translocation of PKC alpha with 15 min and 3 h of treatment but not 1
      min; TNF caused dramatic translocation of PKC alpha at 1 min treatment which
      subsided at 15 min and 3 h but remained significantly elevated; and PMA caused
      dramatic translocation of alpha and epsilon but not zeta. Treatments of
      bradykinin and TNF that translocated PKC also showed cytoskeletal rearrangement
      of rhodamine-phalloidin stained actin, causing it to become more prevalent near
      cell membranes and concentrated at focal points between cells. These results
      suggest that PKC alpha may contribute to long term low grade increases in
      microvessel permeability in response to bradykinin, and that PKC alpha could be
      involved in both transient and sustained microvessel permeability changes induced
      by TNF. Also, cytoskeletal actin organization appears to be a downstream pathway
      in the activation process, possibly leading to alteration in endothelial cell
      shape and contact points.

PMID- 9588825
TI  - Regulated exocytosis in vascular endothelial cells can be triggered by
      intracellular guanine nucleotides and requires a hydrophobic, thiol-sensitive
      component. Studies of regulated von Willebrand factor secretion from digitonin
      permeabilized endothelial cells.
AB  - To study the intracellular events leading to regulated exocytosis in human
      umbilical vein endothelial cells (HUVEC) the plasma membrane of HUVEC was
      selectively permeabilized with digitonin while retaining secretory function.
      Fusion of Weibel-Palade bodies, the secretory organelle of HUVEC, with the plasma
      membrane was detected by assaying the media for von Willebrand factor (vWF). The
      secretion from permeabilized cells faithfully reflects that in intact cells by a
      number of criteria. First, in the presence of calcium, permeabilized HUVEC
      secreted vWF with the same kinetics and to the same extent as intact cells
      stimulated with secretagogue. In addition, the vWF secreted by permeabilized
      cells after stimulus was exclusively the processed mature form found in Weibel
      Palade bodies. Release required micromolar levels of calcium. In addition,
      GTPgammaS could also stimulate release by a parallel pathway. Both calcium- and
      GTPgammaS-stimulated secretion required a thiol-sensitive component. The
      hydrophobic thiol alkylating agent U73122 inhibited calcium-dependent and
      GTPgammaS-stimulated secretion. Surprisingly, N-ethylmaleimide, a hydrophilic
      alkylating agent, did not inhibit secretion. The N-ethylmaleimide-sensitive
      fusion protein (NSF), a protein implicated in a variety of vesicle fusion events,
      did not appear to be the target of U73122. These data strongly suggests the
      participation of a non-NSF, membrane-associated protein in regulated secretion in
      endothelial cells. Further, there appear to be two parallel pathways leading to
      secretion in HUVEC, one stimulated by elevated levels of calcium and the other
      mediated by a GTP-binding protein.

PMID- 9588824
TI  - Flow relaxation is not ATP-mediated in the rabbit ear artery.
AB  - ATP has been proposed to play a role in flow-induced dilation of blood vessels.
      Changes in flow would alter the concentration of ATP at lumenal endothelial P2Y
      receptors, occupation of which results in dilation. We tested the hypothesis that
      the lumenal release of ATP close its receptors on the endothelium and the
      subsequent influence of flow rate on its concentration at such receptors acts as
      a flow sensing system. The effect of the selective P2Y-purinoceptor antagonist
      reactive blue 2 on relaxation of the isolated rabbit ear resistance artery to
      flow, ATP and ACh was studied. We found that reactive blue 2 (100 micromol/L)
      significantly inhibited ATP-induced relaxation, but had no effect on equivalent
      relaxation induced by intraluminal flow (10-40 microl/min). It reduced ACh
      induced relaxation to a less extent. These findings strongly suggest that flow
      induced relaxation of the rabbit ear resistance artery can occur without the
      mediation of locally released ATP.

PMID- 9588826
TI  - Tolerance and immunity in the mucosal immune system. Introduction.

PMID- 9588827
TI  - Peyer's patch dendritic cells and the induction of mucosal immune responses.

PMID- 9588828
TI  - The role of the epithelium in mucosal immunity.

PMID- 9588829
TI  - The mechanism of cholera toxin adjuvanticity.

PMID- 9588830
TI  - Adjuvants or live delivery systems for the characterization of mucosal T helper
      subset responses.

PMID- 9588831
TI  - Oral tolerance: cytokine milieu in the gut and modulation of tolerance by
      cytokines.

PMID- 9588832
TI  - The role of clonal deletion and anergy in oral tolerance.

PMID- 9588833
TI  - Bystander suppression induced by oral tolerance.

PMID- 9588834
TI  - Oral tolerance and its modulation by anti-cytokines.

PMID- 9588835
TI  - The role of gammadelta TCR-bearing T cells in oral tolerance.

PMID- 9588836
TI  - The influence of normal microbial flora on the development of chronic mucosal
      inflammation.

PMID- 9588837
TI  - CD4+ T-cells in the regulation of inflammatory responses in the intestine.

PMID- 9588838
TI  - Induction of colitis in IL2-deficient-mice: the role of thymic and peripheral
      dysregulation in the generation of autoreactive T cells.

PMID- 9588839
TI  - Responses to self and non-self intestinal microflora in health and inflammatory
      bowel disease.

PMID- 9588840
TI  - Viral targets for antisense oligonucleotides: a mini review.

PMID- 9588841
TI  - How to overcome resistance of influenza A viruses against adamantane derivatives.
AB  - We tested two approaches to overcoming resistance of influenza A viruses against
      adamantane derivatives. First, adamantane derivatives that interfere with the ion
      channel function of the variant M2 protein of amantadine-resistant viruses may
      prevent drug resistance, if they are used in mixture with amantadine. Second,
      amantadine acts on the M2 protein (at low concentrations) and indirectly on the
      hemagglutinin (at concentrations at least 100 times higher). Identifying and
      using a drug that reacted with both targets at the same concentration might
      reduce development of resistance, since, in this case, two mutations, one in each
      target protein would be necessary at once. Such a double mutation is assumed to
      be a rare event. We evaluated forty adamantane derivatives and two related
      compounds to determine whether they interfered with plaque formation by influenza
      A strains, including A/Singapore/1/57 (H2N2). Variants resistant to drugs that
      interfered at low concentrations (approximately 1 microg/ml; e.g. amantadine)
      were cross-resistant with each other, but were sensitive to those agents
      effective at high concentrations (8 microg/ml; e.g. memantine). The former group
      of compounds act on the ion channel; the corresponding escape mutants tested had
      amino acid replacements at positions 27, 30 or 31 of the M2 protein.
      Hemagglutinin was the indirect target of the latter group of compounds. Variants
      resistant to these agents lacked amino acid replacements within the ion channel
      of the M2 protein and the mutants tested had amino acid replacements in the
      hemagglutinin. Although we failed to identify compounds that interacted with the
      ion channel of amantadine-resistant variants and inhibited their replication, we
      were able to construct at least two compounds that interfered with both the ion
      channel and the hemagglutinin at about the same concentration. After passage in
      the presence of these compounds, we either failed to obtain any drug-resistant
      mutants or those obtained had amino acid replacements in the ion channel of the
      M2 protein and the hemagglutinin.

PMID- 9588842
TI  - A novel drug screening assay for papillomavirus specific antiviral activity.
AB  - Discovery and development of human papillomavirus (HPV) specific antiviral agents
      have been hampered by the lack of an in vitro assay permissive to HPV
      replication. An experimental assay system for monitoring HPV-11 DNA replication
      has been optimized for use as a papillomavirus antiviral drug screening tool.
      Cloned HPV DNA was introduced into SCC-4 cells by electroporation and viral DNA
      replication monitored by Southern blot. Kinetic studies demonstrated an increased
      HPV genome copy number with time. Viral DNA replicated as episomal, unit length
      genome and remained episomal after multiple passages. These data suggested the
      basis for an in vitro replication assay for evaluating the antiviral activity of
      potential chemotherapeutic agents directly on HPV. This model was used to
      investigate antiviral activities of current anti-HPV therapies such as 5
      fluorouracil (5-FU) and alpha-interferon (alpha-IFN) and potential therapies such
      as sodium butyrate, 5-bromo-20-deoxyuridine (BrdU) and antisense
      oligonucleotides. HPV- 11 replication is significantly inhibited by BrdU and
      sodium butyrate; however 5-FU and alpha-IFN did not give consistent dose response
      results. Finally, ISIS 2105, a 20-mer phosphorothioate antisense oligonucleotide,
      which targets HPV-11 E2 gene product, showed potent antiviral activity in this
      assay with an IC50 of approximately 70 nM.

PMID- 9588843
TI  - Inhibition of influenza virus infections in mice by GS4104, an orally effective
      influenza virus neuraminidase inhibitor.
AB  - The carbocyclic transition state sialic acid analog GS4071 ([3R,4R,5S]-4
      acetamido-5-amino-3-[1-ethylpropoxy]-1-cyclohexane-1 -carboxylic acid), a potent
      influenza virus neuraminidase inhibitor, was highly inhibitory to influenza
      A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), A/Shangdong/09/93 (H3N2) and B/Hong
      Kong/5/72 viruses in Madin Darby canine kidney (MDCK) cells. The 50% effective
      concentrations in these experiments ranged from 1.8 to 59.5 microM, with no
      cytotoxicity evident at 1000 microM, using inhibition of viral cytopathic effect
      determined visually and by neutral red dye uptake. The ethyl ester prodrug of
      GS4071, GS4104, administered by oral gavage (p.o.), had significant inhibitory
      effects on infections in mice induced by these viruses. Antiviral effects were
      seen as prevention of death, increase in mean day to death, inhibition of decline
      of arterial oxygen saturation, lessened lung consolidation and inhibition of
      infectious virus recovered from the lungs. No toxicity was seen in dosages up to
      100 mg/kg/day (highest evaluated). Comparison experiments run versus the
      influenza A (H1N1) virus-induced infection using GS4104, GS4071 and the
      neuraminidase inhibitor zanamivir (GG167, 4-guanidino-Neu5Ac2en), all
      administered p.o., indicated a 10-fold or greater potency for inhibiting the
      infection by GS4104. The minimum effective dosage for GS4104 was 0.1 mg/kg/day,
      with the compound administered twice daily for 5 days beginning 4 h pre-virus
      exposure. Oral therapy with GS4104 could be delayed from 48 to at least 60 h
      after exposure of mice to influenza A (H1N1) virus and still render a significant
      antiviral effect, the time of delay being dependent on the viral challenge dose.
      Intranasal instillation of GS4071 and GG167 to mice infected with influenza virus
      was highly inhibitory to the infection, the minimum effective dosages to
      significantly prevent death being 0.01 mg/kg/day for GS4071 and 0.1 mg/kg/day for
      GG167. Caging of infected mice treated with 10 mg/kg/day of GS4104 with infected
      saline-treated animals did not transfer any influenza-inhibitory effect to the
      latter animals. These data provide strong evidence of the potential of orally
      administered GS4104 for treatment of influenza A and B virus infections in
      humans.

PMID- 9588844
TI  - In vitro anti-influenza virus activity of a plant preparation from Geranium
      sanguineum L.
AB  - A polyphenolic complex (PC), isolated from the Bulgarian medicinal plant Geranium
      sanguineum L., was shown to have selective anti-influenza activity in vitro.
      Expression of HA on the surface of cells infected with A/chicken/Rostock/34,
      virus-induced cytopathic effect, infectious virus yield and plaque formation were
      all reduced at non-toxic concentrations of PC. Synthesis of virus proteins was
      also selectively inhibited. High concentrations of PC (> 200 microg/ml) exhibited
      a strong virucidal effect. Although the action was directed against an early
      stage of infection (within 3 h of infection), the process directly affected was
      not identified. The selectivity of antiviral action was confirmed by the
      variation in sensitivity of different influenza viruses to PC and the selection
      of variants with reduced drug sensitivity.

PMID- 9588845
TI  - Baicalin, an inhibitor of HIV-1 production in vitro.
AB  - The flavonoid baicalin markedly inhibits replication of human immunodeficiency
      virus type 1 (HIV-1) in a concentration-dependent manner in normal peripheral
      blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA) in vitro.
      The effect was more pronounced when the cells were pretreated with baicalin.
      Furthermore, baicalin inhibits HIV-1 replication in PHA-stimulated PBMC from
      asymptomatic HIV-1-seropositive carriers. The 50% inhibitory concentration for
      HIV-1 replication was approximately 0.5 microg/ml. At the concentration of 2
      microg/ml of baicalin, copy numbers of HIV-1 proviral DNA were approximately 50
      times less than in untreated controls. In a cell-free infection system, baicalin
      inhibited the activity of HIV-1 reverse transcriptase (RT), but not the activity
      of human DNA polymerases alpha and gamma (DNA polymerase beta was slightly
      inhibited), suggesting that the anti-HIV-1 effect of baicalin may at least partly
      be due to inhibition of HIV-1 RT.

PMID- 9588846
TI  - Intact, injured, necrotic and apoptotic cells after focal cerebral ischemia in
      the rat.
AB  - Middle cerebral artery occlusion (MCAo) leads to brain cell death. However,
      quantitation of injured brain cells and inflammatory cells after MCAo has not
      been determined in the rat. Transient (2 h) MCAo was therefore induced in male
      Wistar rats by means of an intraluminal monofilament. Immunohistochemical and
      histochemical procedures performed at 46 h after MCAo were used to identify
      specific cellular populations in ischemic and control rats (n = 11). In the
      ischemic core of the lesion, approximately 24.7% of cells disappeared. Forty-four
      point eight percent of parenchymal cells consisted of intact (13.0%) or
      reversibly injured swollen (7.6%) and scalloped/shrunken dark (24.2%) cells. The
      percentage of irreversibly damaged cells was 55.2%, and included 49.9% necrotic
      cells (10.5% red and 39.4% ghost) and 5.4% apoptotic cells. In the inner boundary
      zone of the lesion, 15.9% of cells disappeared. Viable cells constituted 62.0% of
      all remaining cells. Neutrophils and macrophages were localized to this area. In
      the outer boundary zone of the lesion, 9.0% of cells disappeared. Viable cells
      constituted 91.6% of all remaining cells. The ratio of apoptotic to necrotic
      cells was 1:9, 1:6, 1:13 in the ischemic core, inner and outer boundary zones,
      respectively. Our data suggest the presence of three zones within the ischemic
      lesion: the core, and inner and outer boundaries. At 46 h after 2 h of MCAo the
      ischemic lesion is highly heterogeneous containing relatively large percentages
      of morphologically intact cells, suggesting the possibility of an extended window
      of therapeutic opportunity.

PMID- 9588847
TI  - Epileptiform discharges to extracellular stimuli in rat neocortical slices after
      photothrombotic infarction.
AB  - Seizures are one of the most frequent complications after cerebral ischemia in
      patients. Up to now it is unknown which mechanisms are responsible for this. As
      shown previously photothrombotic infarction in rat neocortex leads to a sweeping
      suppression of GABAergic inhibition. In this study we investigated whether and to
      what extent epileptiform discharges can be observed in this ischemia model. In
      neocortical slices from lesioned animals we did not find spontaneous epileptic
      activity or paroxysmal depolarisation shifts. However, ipsi- and contralateral to
      a photothrombotic lesion the frequency of double and multiple discharges was
      markedly increased when compared to unlesioned controls. Surprisingly, neither
      the drug lubeluzole which was has been shown to prevent the GABAergic
      disinhibition observed after photothrombotic lesioning of rat neocortex, nor the
      prevention of spreading depressions by the NMDA-receptor antagonist MK-801 during
      lesion induction significantly affected the frequency of epileptiform discharges.
      This indicates that the epileptiform discharges are probably caused by functional
      alterations of glutamatergic receptors.

PMID- 9588849
TI  - Heat strokes: aetiopathogenesis, neurological characteristics, treatment and
      outcome.
AB  - Heat stroke is a thermal insult to the cerebral thermoregulatory system
      controlling heat production and heat dissipation. The thermal insult may be
      environmental as in 'classic heat stroke' or endogenous as in 'exertional heat
      stroke' in joggers or runners. The insult will lead to a steady rise in body core
      temperature to 40 degrees C or more, exhaustion of sweating with hot dry skin and
      central nervous system disturbances ranging from confusion to deep coma.
      Multisystem insult will follow leading to a fatal outcome, if not diagnosed and
      treated promptly. Rapid evaporative cooling and support of vital organs are the
      essential factors in the management of this condition. If treated early, no
      sequelae results, however, pancerebellar syndrome and spastic or flaccid
      paraparesis have been described in a few cases. Limited sun exposure, proper use
      of sunscreens, adequate fluid and electrolyte replacement and acclimatization are
      the key factors for prevention. Despite appropriate prevention and prompt
      treatment, heat stroke is unlikely to be totally prevented, but the mortality has
      improved dramatically to less than 10%.

PMID- 9588848
TI  - Fat distribution and changes in the blood brain barrier in a rat model of
      cerebral arterial fat embolism.
AB  - This study was designed to determine the distribution of fat which reaches the
      brain by the internal carotid artery, and the consequent alterations in the blood
      brain barrier, in a rat model of cerebral arterial fat embolism. The distribution
      of the blood flow in this model was determined by the injection of radiolabelled
      microspheres. Over 44% were trapped in the brain, 43% in the extracerebral
      tissues of the head and neck, and 7% in the lungs. Over 30% of radiolabelled
      triolein was present within the brain 30 min after injection, and 4% still
      remained after 17 days. Approximately 25% of the triolein which went to the brain
      moved through the cerebral vessels and left within the first 15 min. The majority
      of the triolein distributed to the ipsilateral cerebral hemisphere, with
      significantly less to the contralateral cerebral hemisphere, brain stem and
      cerebellum. The blood brain barrier opened, as measured by uptake of 99mTc,
      within the first 15 min and remained open for at least 3 days. A significant
      percentage of fat reaching the brain persists for days, and causes rapid and long
      lasting damage to the blood brain barrier.

PMID- 9588851
TI  - Preliminary clinical-radiological assessment of a MR tissue signature model in
      human stroke.
AB  - We evaluated the ability of an MR signature model (SM) of cerebral ischemic
      injury to stage the evolution of cellular damage in human stroke. In 19 patients
      with ischemic stroke of presumed embolic or non-embolic cause we carried out
      diffusion-weighted and T2-weighted MR imaging within 48 h of onset, and obtained
      apparent diffusion coefficient of water (ADCw), and T2 weighted images. We used
      the signatures obtained from these ADCw/T2 maps to formulate two patterns of
      damage signifying accelerated or non-accelerated progression of cellular death
      after stroke onset. Those patients with the accelerated pattern corresponded to
      those with the neuroradiological (NRC) and clinical diagnosis (TOAST.1 and
      TOAST.2) of presumed embolic stroke, with clinical diagnosis performed blinded
      both to NRC and to SM. Agreement between the SM and NRC was substantial
      (kappa=0.62), moderate (0.60<kappa<0.40) between the SM or NRC and TOAST.2, and
      fair (0.40<kappa<0.20) among the SM or NRC and TOAST.1. We believe these results
      constitute a preliminary validation of the MR tissue signature modeling in
      clinical stroke assessment.

PMID- 9588850
TI  - Machado-Joseph disease in three Scandinavian families.
AB  - Machado-Joseph disease (MJD) is an autosomal dominantly inherited
      neurodegenerative disorder characterized by varying age of onset and pronounced
      phenotypic heterogeneity. The clinical core features include gait ataxia,
      external ophthalmoplegia, nystagmus, and bulging eyes. Recently, Kawagushi et al.
      (1994) cloned the MJD1 gene on chromosome 14 and MJD turned out to be the fifth
      neurodegenerative disease caused by an unstable CAG repeat expansion. We have
      studied two large Danish families and one Norwegian family with MJD. Three
      features not previously associated with MJD are reported: dementia, generalized
      muscle and joint pain, and in one case neuropathological examination revealed
      atrophy of the inferior olives. We found a significant inverse correlation
      between age of onset and the length of the CAG repeat expansion, and anticipation
      is described through four succeeding generations. Instability of the CAG repeat
      expansion was most pronounced at paternal transmission.

PMID- 9588852
TI  - A small direct tandem duplication of the myelin protein zero gene in a patient
      with Dejerine-Sottas disease phenotype.
AB  - We present a male patient with Dejerine-Sottas disease phenotype, who had a small
      direct tandem duplication of the Po gene. The pathology of the sural nerve showed
      hypomyelinated fibers with absence of active demyelination and onion-bulb
      formations composed of two parallel layers of basement membrane, consistent with
      congenital hypomyelination neuropathy (CHN). However, his clinical features were
      more severe than those of previously reported CHN patients. A GGCA insertion was
      identified at the position of nucleotide 560 in the myelin protein zero (Po)
      gene. This insertional mutation was located in exon 4 coding for the
      transmembrane domain of the Po gene and caused a shift of reading frame, creating
      a stop codon. The mutation of the transmembrane domain probably has the largest
      impact on Po function. The mutation was not identified in both parents.

PMID- 9588854
TI  - Supplemental therapy in isolated vitamin E deficiency improves the peripheral
      neuropathy and prevents the progression of ataxia.
AB  - A 24-year-old male, who suffered since childhood from a progressive form of
      ataxia associated with peripheral neuropathy, was found severely deficient in
      serum vitamin E. He walked with bilateral aid and presented severe dysmetria of
      the limbs and dysarthric speech; muscular strength and trophism were slightly
      diminished in the distal muscles of four limbs and there was hypotonia of the
      arms; he presented absent deep tendon reflexes, bilateral Babinski's sign,
      reduced proprioception at four limbs, pes cavus and fasciculations of the tongue.
      Intestinal fat malabsorption and other gastrointestinal or haematological
      conditions associated with deficiency of this vitamin were ruled out. In this
      patient, after 2 years of a daily supplement of high doses of vitamin E, a
      further progression of the disease was not observed and, moreover, the
      neurophysiological characteristics of his neuropathy appeared clearly improved. A
      longitudinal evaluation of serum vitamin E levels showed values in the normal
      range after 13 months of therapy. The patient had molecular genetic analysis of
      chromosome 8 and was found homozygous for the unusual mutation 513insTT in the
      alpha-tocopherol transfer protein gene.

PMID- 9588853
TI  - Histochemical detection of 4-hydroxynonenal protein in Alzheimer amyloid.
AB  - The presence of lipid peroxidation product in amyloid deposits from seven
      patients with Alzheimer disease and nine with non-Alzheimer disease was examined
      immunohistochemically by means of an affinity purified anti-HNE antibody to
      hydroxynonenal (HNE), a marker of lipid peroxidation. A positive reaction was
      found in amyloid deposits in all the specimens examined: most of the perivascular
      areas (89%) where amyloid deposition was confirmed by Congo red staining, showed
      immunoreactivity with the antibody in the specimens of Alzheimer disease. Twenty
      one percent of senile plaques which were also stained by Congo red staining
      reacted with this antibody. Several perivascular cells were also stained by anti
      HNE antibody. In other neurons both in Alzheimer and non-Alzheimer disease
      patients, only a few percent reacted with this antibody and no statistical
      difference was observed between them. These results verify that lipid
      peroxidation via free radical injury occurs in amyloid deposits in Alzheimer
      amyloid. Since HNE has been identified as a cytotoxic metabolite of free radical
      injury, amyloid deposits in the tissue may exhibit a toxic effect during the
      generation process of HNE.

PMID- 9588855
TI  - Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan: CAG
      trinucleotide expansion and clinical characteristics.
AB  - We analyzed 13 patients with spinocerebellar ataxia type 2 (SCA2) in seven
      unrelated families who live in Gunma Prefecture, Japan (population approx.
      2,000,000), and documented the clinical and molecular properties correlated with
      the CAG repeat expansion. Twelve of the 13 patients and one presymptomatic female
      were genetically examined, and the CAG repeat number of the expanded and normal
      alleles was 40.8+/-4.8 (mean+/-S.D., n=13) and 22+/-0 (n=13), respectively. The
      repeat size of the expanded alleles was inversely correlated with the patients'
      age at onset. Paternal anticipation was observed, accompanied by an increase of
      the CAG repeat size. The patients presented here were clinically characterized by
      a relatively higher frequency of slow saccades, hyporeflexia, hypotonia, and
      tremor. A number of peaks in the expanded allele on polyacrylamide gel
      electrophoresis showed the presence of cell mosaicism in SCA2 as well. In Gunma
      Prefecture, SCA2, Machado-Joseph disease and spinocerebellar ataxia type 6 are
      almost equally present and at higher frequencies than spinocerebellar ataxia type
      1 and hereditary dentatorubropallidoluysian atrophy, which are rare. Thus, the
      difference of frequency of autosomal dominant spinocerebellar ataxias may be
      present in Japan.

PMID- 9588856
TI  - Visual evoked cortical magnetic responses to checkerboard pattern reversal
      stimulation: a study on the neural generators of N75, P100 and N145.
AB  - In an attempt to elucidate the neural generators of pattern reversal visual
      evoked potentials (PR-VEPs), we measured the visual evoked magnetic fields (PR
      VEFs) using a 37-channel magnetoencephalography in six healthy young adults. A
      half-field checkerboard pattern was phase-reversed at a rate of 1 Hz to stimulate
      the right or left visual half-field, thus yielding 12 PR-VEFs in total from the
      six subjects. The simultaneously recorded scalp PR-VEPs showed three distinct
      components of N75, P100 and N145. Three corresponding components were also
      identified in the PR-VEFs with similar peak latencies (N75m, P100m and N145m).
      P100m and N145m were clearly identified in all 12 PR-VEFs, whereas N75m was
      observed in only nine of 12 PR-VEFs. The equivalent current dipoles (ECDs) of
      N75m, P100m and N145m were located closely to each other in the occipital cortex
      around the calcarine fissure contralateral to the stimulated visual field, when
      they were overlaid on the MRI. The reliability of dipole estimation was highest
      in P100m, followed by N145m while N75m showed the least reliability. The
      direction of the current flow of ECDs of N75m and N145m was from the medial to
      the lateral in the occipital cortex when viewed in a coronal section, whereas
      that for P100m was toward the medial. The ECD location of P100m changed according
      to the retinotopic organization when the upper or lower quadrant of the visual
      field was stimulated, with the ECDs being located in the lower or upper part,
      respectively, of the visual cortex. Our results therefore indicate that the
      neural origins of N75m, P100m and N145m of PR-VEFs are in the primary visual
      cortex on the contralateral side of the stimulated visual half-field, while the
      three components are physiologically distinct.

PMID- 9588857
TI  - Diffusion-weighted MR imaging of the hippocampus and temporal white matter in
      Alzheimer's disease.
AB  - We investigated the changes in water diffusion in the hippocampus and the
      temporal white matter (the temporal stem) in eight patients with possible
      Alzheimer's disease (AD), 10 patients with probable AD, and 10 age-matched
      controls, using coronal diffusion-weighted magnetic resonance (MR) imaging.
      Apparent diffusion coefficients (ADCs) were derived for the three orthogonal axes
      and an index of diffusion anisotropy (IDA = ADC(max-min)/ADC(mean)) was then
      calculated. Although no significant differences were found in ADC and IDA values
      in the hippocampal body between controls and patients, vertical (superior
      inferior) ADC values and ADC(mean) values in the temporal stem of patients with
      AD were significantly higher than those in controls, and IDA values were
      therefore significantly lower in patients with possible or probable AD than those
      in controls. Moreover, IDA values in the temporal stem were significantly
      correlated with the clinical severity. These results suggest that decreased fiber
      density, such as the disruption and loss of axonal membranes or myelin, occur
      early in the temporal stem, probably due to secondary degeneration related to
      grey matter pathology including the medial temporal lobe.

PMID- 9588858
TI  - Schwann cell proliferation as the cause of peripheral neuropathy in
      neurofibromatosis-2.
AB  - We report a 18-year-old man who developed slowly progressing right drop foot.
      Bilateral acoustic neurinoma was found and he was diagnosed as neurofibromatosis
      2. Right sural nerve biopsy showed multiple small onion-bulb-like structures in
      the nerve fascicle. Electronmicroscopic and immunohistochemical studies on this
      structure confirmed cytological characteristics of Schwann cells, while previous
      reports suggest that this structure originates from perineural cells. The present
      report is the first to show both ultrastructurally and immunohistochemically that
      the onion-bulb-like structure is derived from Schwann cell.

PMID- 9588859
TI  - Influence of immobilization on bone mass and bone metabolism in hemiplegic
      elderly patients with a long-standing stroke.
AB  - Significant bone mass reduction occurs in stroke patients on the hemiplegic side
      compared with the intact side, correlating with the degree of paralysis and
      vitamin D deficiency. To evaluate the influence of long-standing immobilization
      on this osteopenia, we measured various serum markers of bone metabolism in 93
      hemiplegic elderly patients with a long-standing stroke and in 37 controls. The
      bone mineral density (BMD) of the second metacarpal was determined bilaterally.
      The scoring of the stroke patients activity was based on the Barthel Index (BI).
      The serum ionized calcium was higher in the patients than in the controls,
      correlating negatively with the BI in the patients. The concentrations of
      parathyroid hormone (PTH), pyridinoline cross-linked carboxy-terminal telopeptide
      of type I collagen and bone Gla protein were normal or low. The serum 25
      hydroxyvitamin D level was low in the patients, correlating positively with the
      BMD on both sides. The serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) level was
      markedly reduced in the patients. Hemiplegia from a stroke can result in
      immobilization hypercalcemia which inhibits PTH secretion and 1,25-[OH]2D
      production. Bone remodelling may have almost reached an equilibrium, resulting in
      a steady rate of bone loss. This and the hypovitaminosis D appear to be the
      dominant causes of immobilization-induced osteopenia in elderly, long-standing
      hemiplegic stroke patients.

PMID- 9588860
TI  - Anti-beta 2-glycoprotein I antibodies bind to central nervous system.
AB  - Anti-beta 2-GPI antibodies (a beta 2-GPI) were found in serum from patients with
      anti-phospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). Since
      a beta 2-GPI are often found in patients with anti-cardiolipin antibodies (aCL),
      their role in thrombosis as well as other central nervous system (CNS)
      manifestations in APS is unclear. We, therefore, investigated whether affinity
      purified a beta 2-GPI bind the CNS. Astrocyte and neuron cell lines and
      histological sections were used as CNS substrates. Indirect immunofluorescence
      and/or streptavidin-biotin-peroxidase techniques revealed that astrocytes,
      neurons and vascular endothelium were bound by purified a beta 2-GPI (mouse
      monoclonal, rabbit polyclonal, human serum Ig a beta 2-GPI). This suggests a
      potential role for a beta 2-GPI in the CNS damage, as a beta 2-GPI might
      contribute to CNS pathology by either a direct interaction with astrocytes and
      neurons or an interaction with cerebral vascular endothelial cells. CNS
      immunoreaction was also demonstrated using six a beta 2-GPI-positive sera from
      patients (four with neurological manifestations). No binding to CNS was seen
      using a beta 2-GPI-negative sera, i.e. five from SLE patients (two with CNS
      involvement) and six healthy donors, or a monoclonal aCL without a beta 2-GPI
      immunoreactivity. Thus, the CNS reactivity by the a beta 2-GPI-positive sera
      appears specifically due to a beta 2-GPI and independent from aCL. Because of the
      presence of aCL in all patient sera, and the CNS involvement in three control
      patients, it is not possible to attribute a direct role for a beta 2-GPI in
      neurological diseases in this study.

PMID- 9588861
TI  - Subtypes and case-fatality rates of stroke: a hospital-based stroke registry in
      Taiwan (SCAN-IV).
AB  - Stroke data bank can afford important information regarding risk factors,
      pathogenesis, prognosis, etc. By means of hospital-based stroke registry, we
      investigated the risk factors and case-fatality rates in different types of
      stroke and transient ischemic attack (TIA) patients at the National Taiwan
      University Hospital in 1995. After excluding ineligible patients, 995 patients
      aged 1-98 years (575 men and 420 women) were recruited. Men predominated in all
      age groups for stroke and TIA in general except for cerebral hemorrhage (CH) in
      patients aged < 35 years and subarachnoid hemorrhage (SAH) in patients aged > or
      = 45 years. Of these, 676 (67.9%), 41 (4.1%), 228 (22.9%) and 50 (5%) patients
      were classified in the categories of cerebral infarction (CI), TIA, CH and SAH,
      respectively. The CI/CH ratio was 2.96. Hypertension remained one of the most
      important risk factors for CI, CH and TIA patients. Severe extracranial carotid
      artery stenosis (> or = 50%) was found in 12% of the CI patients and 27% of the
      TIA patients, but not found in the CH and SAH patients. Of these patients, the 30
      day case-fatality rate was 10.9%, highest in SAH (30%), followed by CH (24.1%)
      and CI (5.6%). There were 41 in-hospital stroke patients who had significantly
      higher case-fatality rates than the other stroke patients (P<0.001 for all
      stroke, CI and CH patients by chi2 test). As compared to the previous stroke
      registries in Taiwan, there is a secular trend of increasing CI/CH ratios. These
      findings in Taiwan were compared with those in other populations, including other
      Asian, Caucasian and black populations. The CI/CH ratios in Asian populations,
      including Chinese, Japanese and Korean, were much lower than those in Caucasian
      and black populations. Dietary, environmental and genetic factors probably play
      important roles in these differences.

PMID- 9588862
TI  - Vitamin E serum levels in Rett syndrome.
AB  - In order to study the role of vitamin E in the pathogenesis of Rett syndrome
      (RS), we analysed vitamin E serum levels in twenty-eight patients affected by
      this disorder. We found lower vitamin E serum levels in nine cases (32.1%). These
      results indicated that the oxidative free radical metabolism may be impaired in a
      significant percentage of Rett syndrome patients suggesting the need for further
      studies of tissue vitamin E in different brain regions.

PMID- 9588863
TI  - Topical liposome targeting of dyes, melanins, genes, and proteins selectively to
      hair follicles.
AB  - For therapeutic and cosmetic modification of hair, we have developed a hair
      follicle-selective macromolecule and small molecule targeting system with topical
      application of phosphatidylcholine-based liposomes. Liposome-entrapped melanins,
      proteins, genes, and small-molecules have been selectively targeted to the hair
      follicle and hair shafts of mice. Liposomal delivery of these molecules is time
      dependent. Negligible amounts of delivered molecules enter the dermis, epidermis,
      or bloodstream thereby demonstrating selective follicle delivery. Naked molecules
      are trapped in the stratum corneum and are unable to enter the follicle. The
      potential of the hair-follicle liposome delivery system for therapeutic use for
      hair disease as well as for cosmesis has been demonstrated in 3-dimensional
      histoculture of hair-growing skin and mouse in vivo models. Topical liposome
      selective delivery to hair follicles has demonstrated the ability to color hair
      with melanin, the delivery of the active lac-Z gene to hair matrix cells and
      delivery of proteins as well. Liposome-targeting of molecules to hair follicles
      has also been achieved in human scalp in histoculture. Liposomes thus have high
      potential in selective hair follicle targeting of large and small molecules,
      including genes, opening the field of gene therapy and other molecular therapy of
      the hair process to restore hair growth, physiologically restore or alter hair
      pigment, and to prevent or accelerate hair loss.

PMID- 9588864
TI  - Rationale for the use of immunotoxins in the treatment of HIV-infected humans.
AB  - The first step in the replication of human immunodeficiency virus (HIV) is
      selective binding of the envelope glycoprotein (gp120) to CD4 receptors on T
      cells or macrophages. After penetration in these cells, the genome of the virus
      is integrated in the human genome. HIV-infection causes depletion of CD4-positive
      cells resulting in a severe immunosuppression. It is believed that eliminating
      HIV-infected cells is crucial in limiting further reduction of CD4-positive cells
      and thus, preventing disease progression. The most commonly used drugs, such as
      zidovudine (AZT), appeared to be not completely effective. Therefore many
      investigators are searching for alternative treatment modalities. The use of
      immunotoxins (ITs) to eliminate HIV-infected cells is discussed. ITs are chimeric
      molecules in which cell-binding ligands are coupled to toxins and can
      specifically eliminate undesired cells. The cell-binding carriers of anti-HIV ITs
      have been directed against different regions of the HIV envelope glycoprotein
      (gp120 and gp41) and surface antigens (e.g CD4, CD25). The ITs have been composed
      of different ribosome-inactivating proteins (RIPs) like pokeweed antiviral
      protein (PAP), Pseudomonas exotoxin (PE), Diphtheria toxin (DT), or ricin. In in
      vitro studies, several of these ITs have been shown to be effective and specific
      in killing acute and persistently HIV-infected cells. The ITs were effective at
      concentrations (ID50 range from 10(-9) M to 10(-12) M) that were not toxic to
      uninfected cells or cells without the antigen. The IT CD4(178)PE40, a fusion
      protein directed against the CD4 binding site of gp120, has been investigated in
      two in vivo trials. The results were disappointing considering the antiviral
      activity in vitro. This was thought to be due to the rapid clearance of the IT
      and the differential resistance of clinical HIV isolates. Use of a panel of ITs
      is likely to be more effective because multiple approaches cover the intrinsic
      variability of HIV and the presence of IT-resistant or latently infected cells,
      as well as the blocking presence of neutralizing anti-HIV antibodies and the
      immunogenicity of most ITs. It may be possible to control the virus completely
      with a panel of ITs in combination with other antiviral or immunosuppressive
      agents such as RT inhibitors (e.g AZT), interferon alpha, or cyclosporine. More
      research will be necessary to develop such a combined therapy.

PMID- 9588865
TI  - The immunological co-adjuvant action of liposomal interleukin-2: the role of mode
      of localisation of the cytokine and antigen in the vesicles.
AB  - In experiments designed to study the co-adjuvant action of interleukin-2, a model
      antigen (tetanus toxoid) was passively entrapped in, or covalently coupled to
      multilamellar liposomes in the presence or absence of interleukin-2 (IL-2). When
      present, IL-2 was either co-entrapped with the toxoid, entrapped alone in
      liposomes with toxoid coupled to their surface, or coupled to the surface of
      liposomes with entrapped toxoid. The role of spatial localization of IL-2 within
      the liposomal structure (vis a vis that of the toxoid) was studied in terms of
      its immunoadjuvant action in vivo. Male CD-1 mice were injected intramuscularly
      twice with a variety of toxoid-containing liposomal preparations in the absence
      or presence of IL-2 incorporated in the same liposomes as above. In some
      experiments mice were immunized with liposomal toxoid mixed with separately
      entrapped IL-2. Results show that IL-2 augments significantly secondary immune
      responses (IgG1, IgGa, IgG2b subclasses) against the liposomal toxoid (up to 15
      fold compared with the liposomal toxoid alone), regardless of cytokine and
      antigen mode of accommodation in the liposomal structure but only when both are
      present in the same vesicles. It is suggested that liposomal IL-2 may prove
      useful as a co-adjuvant for vaccines which are weak or ineffective.

PMID- 9588866
TI  - Surface-modified amikacin-liposomes: organ distribution and interaction with
      plasma proteins.
AB  - Amikacin-loaded liposomes were produced and surface-modified by adsorption of PEG
      4000, Tween 80, poloxamer 407 and gelatin. The organ distribution was studied in
      mice by analysing the amikacin content in liver, spleen, lung, kidneys and serum.
      Highest serum levels were obtained with the PEG- and Tween 80 modified liposomes
      (at 2 hours p.inj.). Modification of the liposomes with gelatin as opsonization
      promoting agent distinctly increased the amikacin concentration in the liver from
      36 to 66 mg/kg. Highest spleen concentrations were observed with non-modified and
      poloxamer 407 liposomes (242 mg/kg and 248 mg/kg, respectively). The data suggest
      that modification by a simple adsorption process is sufficient to effectively
      alter the organ distribution. The liposomes differing in organ distribution
      exhibited also different plasma protein adsorption patterns, up to 115 spots were
      detected by 2-D PAGE. Hydrophilic albumin was present in a conc. of appr. 80% on
      liposomes modified with ethoxylated compounds. On the gelatin liposomes, 14% of
      alpha-2-Macroglobulin were adsorbed which is a protein typically found on
      particles rapidly cleared by the RES. IgM, Apo A-I, Apo C-II and alpha-1
      Antitrypsin were other detected proteins.

PMID- 9588867
TI  - In vitro and in vivo evaluation of human tumor necrosis factor-alpha (hTNFalpha)
      chemically conjugated to monoclonal antibody.
AB  - Human tumor necrosis-alpha (hTNF-alpha) was chemically conjugated to the murine
      anti-Ly-2.1 T cell antibody using heterobifunctional crosslinking agents SAMSA
      and SPDP. SDS-PAGE analysis of the affinity purified conjugate consisted mainly
      of 1:1 and 1:2 (Ly-2.1:TNF) complexes. Conjugated hTNF retained 50% of its
      cytotoxic activity by the L929 cytolytic assay, with an IC50 = 0.12 ng/ml. hTNF
      Ly-2.1 was also cytotoxic to E3 cells (Ly-2.1+ve) with an IC50 = 1.7 microg/ml -
      3 times more cytotoxic to these cells than non-conjugated hTNF in vitro. However
      in vivo hTNF-Ly-2.1 conjugates were more toxic to mice than hTNF. In vivo blood
      clearance studies in E3 tumor bearing CBF1 mice demonstrated that the half life
      of the conjugate was 2 hr, compared to 20 min for hTNF. In biodistribution
      studies, tumor accumulation of 3% was seen for hTNF-Ly-2.1 while for unconjugated
      hTNF no activity in tumor was detected 24hr post injection. A single dose of hTNF
      Ly-2.1 increased the accumulation of 125I-anti-Ly-2.1 by 3 fold compared to
      controls. However, the antitumor effect of hTNF-Ly-2.1 on E3 cells in vivo was
      marginal with some tumor growth retardation at day 1-3. The results of these in
      vitro and in vivo studies on chemically conjugated h-TNF-MoAb will be helpful in
      the design of novel recombinant fusion proteins for targeting the biologic
      activity of TNF to tumours.

PMID- 9588868
TI  - Absorption enhancers as tools to determine the route of nasal absorption of
      peptides.
AB  - The nasal absorption of a series of peptides was studied in order to examine the
      relationship between extent of absorption and lipophilicity and absorption
      enhancers were used to probe the mechanism of peptide absorption. An in situ rat
      nasal perfusion technique was employed to assess the nasal absorption of a series
      of peptides, D-FGGGGG (D-FG5), D-FD-FGGGG (D-F2G4) and D-FD-FD-FGGG (D-F3G3), [D
      ala2, D-leu5]enkephalin (YD-AGFD-L) and thyrotrophin releasing hormone (TRH). The
      enhancers sodium tauro-24,25 dihydrofusidate (STDHF), ethylene diamine
      tetraacetic acid (EDTA and dimethyl-beta-cyclodextrin (DMbetaCD) were utilized to
      improve and elucidate the mechanisms of peptide absorption. There was no
      significant relationship between extent of peptide absorption and lipophilicity
      as determined by C log P values. STDHF was a potent absorption enhancer but
      demonstrated overt toxicity. Conversely, EDTA did not demonstrate extensive
      toxicity but was found to be a poor absorption enhancer. DMbetaCD displayed some
      toxicity and was also found to inhibit the absorption of D-FG5,D-F2G4 and D-F3G3.
      This reduction is likely to be a result of the peptide/DMbetaCD complex
      formation. The peptides studied appear to be predominantly absorbed by a passive
      paracellular mechanism.

PMID- 9588869
TI  - Osteotropic drug delivery system (ODDS) based on bisphosphonic prodrug. I.v.
      effects of osteotropic estradiol on bone mineral density and uterine weight in
      ovariectomized rats.
AB  - An osteotropic drug delivery system (ODDS) based on the bisphosphonic prodrug was
      designed for 17beta-estradiol (E2) in order to improve patient compliance in
      estrogen replacement therapy of postmenopausal osteoporosis. The bisphosphonic
      prodrug of E2, disodium [17beta-(3 '-hydroxy- 1',3',5'-estratrienyloxy)
      carbonylpropyl carboxamidomethylene] bisphosphonate (E2-BP) was synthesized and
      its effects on bone mineral density and uterine weight were investigated in
      ovariectomized (OVX) rats. E2-BP was injected intravenously once a week (4
      injections/experiment), and E2 was administrated orally 5 times a week (20
      administrations/experiment). Once a week treatment with 0.1 mg/kg E2-BP
      significantly restored bone mineral reduction by 61.8% without significantly
      increasing uterine weight. Similarly, once in 4 weeks treatment with 1.0 mg/kg E2
      BP (1 injection/experiment) showed almost the same therapeutic effects. On the
      other hand, 5 times a week oral treatment with 1.0 mg/kg E2 significantly
      improved bone mineral density by 90.5%, but increased uterine weight up to 98.2%
      of that of the sham group. In vitro bone resorption analysis revealed that E2-BP
      exhibits antiresorptive activity not as a bisphosphonate but as a prodrug of E2.
      These results demonstrated that E2-BP has the potential to improve patient
      compliance in estrogen therapy by its minimal adverse effects and less frequent
      medication.

PMID- 9588870
TI  - Pulsatile stretch and shear stress: physical stimuli determining the production
      of endothelium-derived relaxing factors.
AB  - Mechanical forces generated at the endothelium by fluid shear stress and
      pulsatile stretch are important in ensuring the continuous release of vasoactive
      endothelial autacoids. Although the mechanism by which endothelial cells are able
      to detect and convert these physical stimuli into chemical signals is unclear,
      this process involves the activation of integrins, G proteins and cascades of
      protein kinases. The constitutive endothelial nitric oxide synthase (NOS III),
      classified as a Ca2+/calmodulin-dependent isoform, can be activated by shear
      stress and isometric contraction in the absence of a maintained increase in
      [Ca2+]i via a mechanism involving its redistribution within the
      cytoskeleton/caveolae and the activation of one or more regulatory NOS-associated
      proteins. Thus it would appear that the intracellular cascades activated by Ca2+
      elevating receptor-dependent agonists, such as bradykinin, and hemodynamic
      stimuli are distinct. Rhythmic vessel distension is also able to elicit the
      synthesis of superoxide anions and the endothelium-derived hyperpolarizing factor
      which play a role in modulating arterial compliance in certain vascular beds.

PMID- 9588871
TI  - Neural control of coronary blood flow.
AB  - Parasympathetic control of coronary blood flow has been extensively studied in
      dogs, and a clear vasodilator effect not dependent on changes in myocardial
      metabolism was observed. Parasympathetic vasodilatation is mediated via nitric
      oxide (EDRF) and is activated during carotid baroreceptor and chemoreceptor
      reflexes. Intracoronary infusions of acetylcholine in humans results in increased
      coronary blood flow and epicardial coronary artery dilatation except in
      atherosclerotic epicardial coronary vessels, which show a paradoxical
      vasoconstriction. Sympathetic alpha-adrenoceptor-mediated coronary
      vasoconstriction has been repeatedly demonstrated whenever there is adrenergic
      activation of the heart, as during exercise or a carotid sinus baroreceptor
      reflex in dogs or during a cold pressor reflex in humans. Recent evidence
      indicates that there is a beneficial effect of this paradoxical vasoconstrictor
      influence in that it helps preserve flow to the vulnerable inner layer of the
      left ventricle, but only when both heart rate and coronary flow are high. Beta
      adrenoceptor-mediated coronary vasodilatation also occurs during adrenergic
      activation of the heart. The dominant site for beta-vasodilatation is in small
      arterioles, while the dominant site for alpha-vasoconstriction is in microvessels
      larger than approximately 100 microm diameter. The beta-adrenoceptor coronary
      vasodilatation is an example of feedforward open-loop control that complements
      the closed-loop negative feedback control by local metabolic factors. The
      combined feedback and feedforward control mechanism has the advantage of an
      excellent match between coronary blood flow and myocardial oxygen consumption
      with a rapid response time but without the instability inherent in high gain
      feedback systems.

PMID- 9588872
TI  - Stretch-induced collagen synthesis in cultured smooth muscle cells from rabbit
      aortic media and a possible involvement of angiotensin II and transforming growth
      factor-beta.
AB  - Mechanical strain reportedly stimulates the synthesis of collagen in vascular
      smooth muscle cells (SMCs). The present study was designed to investigate a
      possible involvement of angiotensin II (Ang II) and transforming growth factor
      (TGF)-beta in stretch-induced collagen synthesis of cultured SMCs derived from
      the rabbit aortic media. SMCs were cyclically stretched at a rate of 10%
      elongation and 30 cycles/min for 24 h using the Flexercell strain unit (Flexcell
      International Corp., McKeesport, Pa.). A two-fold increase in collagen synthesis
      and a concurrent increase in total protein synthesis were noted in stretched
      SMCs. Concentration of immunoreactive Ang II in the conditioned medium was
      elevated under the mechanical strain. Stretch-induced collagen and total protein
      synthesis were inhibited by either a selective antagonist to Ang II (saralasin),
      an angiotensin I-converting enzyme inhibitor (captopril) or an antisense
      oligonucleotide for angiotensinogen mRNA. An elevated secretion of TGF-beta, both
      active and latent forms, was found in the medium of stretched SMCs. Saralasin
      inhibited the stretch-induced secretion of TGF-beta from SMCs. Stretch-induced
      collagen and total protein synthesis was further inhibited by either an anti-TGF
      beta1 neutralizing antibody or an adenovirus-mediated transfer of a truncated TGF
      beta type II receptor. Elevated expression of collagen alpha1(III) chain and TGF
      beta1 mRNAs, and its reversal by saralasin were also demonstrated in stretched
      SMCs. Results indicate that the stretch-induced collagen and total protein
      synthesis appears to be mediated via an autocrine-paracrine mechanism of Ang II
      and TGF-beta released from SMCs.

PMID- 9588874
TI  - In vitro tumor angiogenesis assays: plasminogen lysine binding site 1 inhibits in
      vitro tumor-induced angiogenesis.
AB  - It is generally accepted that tumors are angiogenesis-dependent. For research and
      clinical purposes it would be very attractive to have a simple in vitro model
      that allows a rapid screening of the angiogenic potential of tumors and to study
      the effect of angiogenic inhibitors. In vitro angiogenesis models were developed,
      based on endothelial sprouting/tube formation on a collagen gel, using both tumor
      cell lines and tumor biopsies. Best results were obtained using conditioned
      medium of tumor cell lines. In this model it was found that the plasminogen
      fragment lysine binding site 1 (LBS-1) inhibited in vitro endothelial cell
      sprouting. This is the first demonstration that LBS-1, which includes
      angiostatin, is inhibitory for new vessel formation in an in vitro angiogenesis
      model. We conclude that the assay system allows for rapid and reliable screening
      of angiogenesis inhibitors.

PMID- 9588873
TI  - Induction of nitric oxide and tetrahydrobiopterin synthesis by lipoteichoic acid
      from Staphylococcus aureus in vascular smooth muscle cells.
AB  - Lipoteichoic acid (LTA), a component of the membrane of gram-positive bacteria,
      induces an isoform of nitric oxide (NO) synthase (iNOS) in vascular smooth
      muscle; this process may be associated with the vascular failure observed in gram
      positive septic shock. The aim of the present work was to study the cellular
      mechanisms involved in the induction of NO synthesis by LTA from Staphylococcus
      aureus in cultured rat vascular smooth muscle cells. LTA induces the gene
      expression of iNOS and GTP cyclohydrolase I (GTPCH) as well as the formation of
      NO and tetrahydrobiopterin (BH4), effects which are synergistic with interferon
      gamma. 2,4-Diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of GTPCH,
      inhibits both the increase in cellular levels of BH4 as well as the concomitant
      formation of NO caused by LTA in combination with interferon-gamma. This
      inhibition by DAHP is reversed by co-addition of sepiapterin which is a substrate
      for BH4 synthesis. Thus, BH4 synthesis is an absolute requirement for the
      induction of NO synthesis by LTA in vascular smooth muscle. Our findings also
      suggest that interrupting pterin synthesis may be an effective target for
      pharmacologic interventions aimed at limiting NO overproduction in gram-positive
      shock.

PMID- 9588875
TI  - Abnormal deposition of extracellular matrix proteins by cultured smooth muscle
      cells from human varicose veins.
AB  - The aim of the present study was to verify whether the modifications of the
      extracellular matrix, described in varicose veins, are also present in cultures
      of smooth muscle cells from human varicose veins. The accumulation of collagen
      type III and fibronectin was determined by immunofluorescence in cultures of
      smooth muscle cells at passage 2-3 during the proliferation phase. After 5 days
      of culture, the immunostaining of both collagen type III and fibronectin was
      weaker in cells from varicose than in those of control veins while the expression
      of collagen type III and fibronectin messenger ribonucleic acids was not
      significantly different. Collagen type I and III synthesis were quantified by
      tritiated proline incorporation in control and varicose cell layers at
      postconfluence. Collagen type I deposition was similar in both types of cell
      layers while collagen type III was decreased in cell layers from varicose veins.
      Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) were also
      quantified by enzyme immunoassays in supernatants from smooth muscle cell
      cultures at postconfluence. No significant difference was observed in the
      synthesis of any of the MMPs (-1, -2 and -9) or their inhibitors (-1 and -2)
      tested. These data illustrate that smooth muscle cells cultured from varicose
      veins deposit less collagen type III and fibronectin than control cells despite
      comparable levels of mRNAs for these proteins suggesting dysregulation of
      posttranslational steps in the synthesis of both proteins by smooth muscle cells
      from varicose veins.

PMID- 9588876
TI  - Effects of chemical sympathectomy on angiotensin II-induced neointimal growth in
      the balloon-injured rat carotid artery.
AB  - To investigate the role of the sympathetic nervous system in angiotensin II
      (AngII)-stimulated medial and neointimal smooth muscle cell (SMC) replication, we
      sympathectomized rats with 6-hydroxydopamine (6-OHDA) in which the left carotid
      artery was injured by a balloon catheter. Balloon injury is associated with a
      loss of specific [3H]-prazosin binding. AngII (250 ng/kg/min), infused 2 weeks
      after balloon injury of the rat left carotid artery, increased systolic blood
      pressure by approximately 70 mm Hg. There was no effect of 6-OHDA on this pressor
      response. AngII increased the cumulative 5-bromo-2'-deoxyuridine (BrdU) labeling
      fraction (LF) in the uninjured right carotid media and the injured left carotid
      neointima as compared to controls (5.7+/-1.6% vs. 0.4+/-0.1%, p<0.05; 10.6+/-0.9%
      vs. 5.0+/-0.8%, p<0.05, respectively). 6-OHDA decreased the AngII-induced
      increase in LF in the media of the uninjured right carotid artery (AngII/6-OHDA
      0.9+/-0.2% vs. AngII 5.7+/-1.6%, p < 0.05). 6-OHDA did not decrease the AngII
      induced increase in LF in both the injured left carotid media and neointima at 4
      weeks after balloon injury. The effects of chemical sympathectomy were comparable
      with those obtained 12 weeks after balloon injury. Thus, the data show that the
      sympathetic nervous system mediates the AngII-induced increase in SMC DNA
      synthesis, but only in the uninjured carotid media. This indicates a differential
      regulation of AngII-induced SMC replication in injured and uninjured vessels.

PMID- 9588879
TI  - Direct action of estrogen on sequence of progression of human preneoplastic
      breast disease.
AB  - We have used the MCF10AT xenograft model of human proliferative breast disease to
      examine the early effects of estradiol exposure on morphological progression of
      preneoplastic lesions and to define the step(s) in the morphological sequence at
      which estrogen may act. The effects of estradiol on neoplastic progression of
      estrogen-receptor-positive MCF10AT cells in the orthotopic site were examined in
      ovariectomized female nude mice that received subcutaneous administration of
      implants of 17beta-estradiol or placebo pellets. At 10 weeks, histological
      analysis of the lesions derived from the estrogen-supplemented group revealed
      that 92% of lesions displayed histological features of atypical hyperplasia,
      carcinoma in situ, or invasive carcinoma, and the remaining 8% exhibited
      histological features of moderate hyperplasia. These highly proliferative lesions
      are in marked contrast to the control group in which 60% of samples displayed no
      evidence of hyperplasia. In contrast with control xenografts, estrogen-exposed
      xenografts demonstrated extensive areas of papillary growth, adenosis-like areas,
      prominent host inflammatory infiltration, and angiogenesis. Our results suggest
      that estrogen exerts a growth-promoting effect on benign or premalignant ductal
      epithelium by enhancing 1) the frequency of lesion formation, 2) the size of
      lesions, 3) the speed of transformation from normal/mild hyperplasia to those
      with atypia, 4) the degree of dysplasia, and 5) angiogenesis.

PMID- 9588878
TI  - The pathogenesis of amyloidosis: understanding general principles.

PMID- 9588877
TI  - DNA copy number amplifications in human neoplasms: review of comparative genomic
      hybridization studies.
AB  - This review summarizes reports of recurrent DNA sequence copy number
      amplifications in human neoplasms detected by comparative genomic hybridization.
      Some of the chromosomal areas with recurrent DNA copy number amplifications
      (amplicons) of 1p22-p31, 1p32-p36, 1q, 2p13-p16, 2p23-p25, 2q31-q33, 3q, 5p, 6p12
      pter, 7p12-p13, 7q11.2, 7q21-q22, 8p11-p12, 8q, 11q13-q14, 12p, 12q13-q21, 13q14,
      13q22-qter, 14q13-q21, 15q24-qter, 17p11.2-p12, 17q12-q21, 17q22-qter, 18q,
      19p13.2-pter, 19cen-q13.3, 20p11.2-p12, 20q, Xp11.2-p21, and Xp11-q13 and genes
      therein are presented in more detail. The paper with more than 150 references and
      two tables can be accessed from our web site
      http://www.helsinki.fi/lglvwww/CMG.html. The data will be updated biannually
      until the year 2001.

PMID- 9588880
TI  - Activated keratinocytes in the epidermis of hypertrophic scars.
AB  - The etiology of hypertrophic scarring, a pathological end point of wound healing,
      is unknown. The scars most commonly occur when epithelialization has been delayed
      during, for example, the healing of deep dermal burn wounds. Hypertrophic scars
      are conventionally described as a dermal pathology in which the epidermis has
      only a passive role. In this study, the expression of keratin intermediate
      filament proteins and filaggrin has been investigated in the epidermis of
      hypertrophic scars and site-matched controls from the same patients. Hypertrophic
      scar epidermis was found to express the hyperproliferative keratins K6 and K16 in
      interfollicular epidermis in association with K17 and precocious expression of
      filaggrin. K16 mRNA was localized by in situ hybridization using a highly
      specific cRNA probe. In contrast to the immunohistochemical location of K16
      protein, the K16 mRNA was found to be expressed in the basal cell layer of normal
      skin. In hypertrophic scars the mRNA distribution corroborated the abnormal K16
      protein distribution. These results suggest the keratinocytes in hypertrophic
      scar epidermis have entered an alternative differentiation pathway and are
      expressing an activated phenotype. Activated keratinocytes are a feature of the
      early stages of wound healing producing growth factors that influence
      fibroblasts, endothelial cells, and the inflammatory response. We propose that
      cellular mechanisms in the pathogenesis of hypertrophic scarring are more complex
      than isolated dermal phenomena. The persistence of activated keratinocytes in
      hypertrophic scar epidermis implicates abnormal epidermal-mesenchymal
      interactions.

PMID- 9588881
TI  - Langerhans cells in Langerhans cell granulomatosis are not actively proliferating
      cells.
AB  - Pulmonary Langerhans cell granulomatosis (LCG), also called histiocytosis X, is a
      disorder of unknown etiology characterized by the presence of destructive
      granulomas containing numerous Langerhans cells (LCs). The process may be
      localized or multifocal, and it remains unclear whether the same pathogenic
      mechanism is involved in all forms of the disease. It is often assumed that the
      massive accumulation of LCs at the sites of the lesions results from the abnormal
      proliferation of these cells, although it has been suggested that LCG in adults,
      at least in the lung, could be a reactive disorder initiated by activated LCs.
      Little is known, however, concerning the mechanisms responsible for the
      accumulation of large numbers of LCs in the course of the disease, and the
      relative contribution of recruitment and local proliferation of these cells
      remains to be established. To investigate this question, the proportion of
      replicating LCs was evaluated in biopsied granulomas from patients with localized
      or diffuse form of LCG by means of several histopathological techniques currently
      used in assessment of cell proliferation. The findings demonstrate that, except
      for proliferating cell nuclear antigen (PCNA), all parameters measured are low in
      all forms of the disease. They are similar to those of renewing epithelial cells
      and clearly less than those of neoplastic cells. These data strongly suggest that
      LCs in LCG granulomas are not a rapidly dividing cell population and that local
      LC replication makes only a minimal contribution to granuloma maintenance.
      Caution appears to be necessary in the use of PCNA as a marker of growth
      fraction.

PMID- 9588882
TI  - Oxidative stress causes relocation of the lysosomal enzyme cathepsin D with
      ensuing apoptosis in neonatal rat cardiomyocytes.
AB  - Exposing neonatal rat heart myocytes to the redox cycling quinone naphthazarin
      (5,8-dihydroxy-1,4-naphthoquinone) for 15 to 45 minutes led to a time-dependent
      release of cathepsin D from many secondary lysosomes to the cytosol, as analyzed
      by morphometry. Cathepsin D was detected electron microscopically using a pre
      embedding immunostaining technique that utilizes antibodies conjugated to ultra
      small (0.8-nm) gold particles and subsequent silver enhancement. The exposure to
      naphthazarin also caused a decrease in both the pH and the ATP level of the cells
      within the same time frame. Lipid peroxidation was, however, not detected.
      Pretreatment of the cultures with alpha-tocopherol succinate prevented cathepsin
      D relocation, as shown by immunofluorescence. After exposure to naphthazarin,
      cells were washed, and normal culture conditions were re-established for 18
      hours. Many cells then showed apoptotic morphology (ie, cellular shrinkage and
      chromatin condensation) as analyzed by Giemsa staining. Also, 41% of the cells
      stained positive with the TUNEL technique, and DNA fragmentation was detected by
      separation of intact and fragmented DNA. Apoptosis was significantly decreased in
      cultures pretreated with alpha-tocopherol succinate.

PMID- 9588883
TI  - Expression patterns of CD44 adhesion molecule in testicular germ cell tumors and
      normal testes.
AB  - Despite recent extensive immunohistochemical studies, the expression patterns of
      CD44 in testicular germ cell tumors are still controversial. In the present
      study, we investigated the CD44 gene expression in 40 specimens including 18
      seminomas, 16 nonseminomatous germ cell tumors (NSGCT), and 6 normal testes by
      reverse transcriptase-polymerase chain reaction and Western blotting. Reverse
      transcriptase-polymerase chain reaction analysis revealed that the standard CD44
      isoform (CD44s) was expressed in all of the specimens, whereas the variant CD44
      isoforms were highly expressed in NSGCTs but barely detectable in seminomas and
      normal testes. In addition, we confirmed by direct DNA sequence analysis that the
      predominantly expressed variant isoform in NSGCTs was CD44v8-10. In germ cell
      tumors, these results were paralleled in Western blot analysis; that is, CD44s
      protein was expressed in all of the tumor specimens, whereas high molecular
      weight variant isoforms were expressed only in NSGCTs. However, at the protein
      level, no detectable CD44 was expressed in normal testes. These findings show
      that the combined assessment of CD44 expression patterns at both the RNA and
      protein levels enables us to distinguish among seminoma, NSGCT, and normal testis
      specimens; hence, it could serve as a useful practical adjunct to conventional
      diagnostic methods for testicular germ cell tumors.

PMID- 9588885
TI  - Chlamydial elementary bodies are translocated on the surface of epithelial cells.
AB  - Infection of eukaryotic cells by intracellular pathogens such as chlamydia
      requires attachment to the host cell surface. Chlamydia are thought to attach to
      the tips of microvilli in confluent monolayers of polarized cells. In vitro
      evidence obtained from migrating epithelial cells suggested that during healing
      the route of pathogen uptake might be different from that in intact epithelia.
      The small size of infectious chlamydial elementary bodies (approximately 0.3
      microm in diameter) has made it difficult, however, to analyze the early stages
      of pathogen-host cell interaction in living cells by conventional microscopy.
      Contrast-enhanced video microscopy was therefore used to examine the earliest
      events of host-pathogen interaction and test the hypothesis that chlamydial
      uptake into the healing epithelia can involve translocation over the host cell
      surface. Observations made in this way were validated by scanning and
      immunofluorescence microscopy. These studies revealed two fates for chlamydiae
      taken onto the lamellipodial surface: 1) some chlamydiae were moved in a random
      fashion on the cell surface or were detached into the culture medium, whereas 2)
      other chlamydiae were translocated across the lamellipodium in a highly directed
      manner toward the microvillous perinuclear region. After internalization, these
      latter chlamydiae were found within intracellular inclusions, which demonstrated
      that this route of attachment and location of uptake resulted in productive
      growth.

PMID- 9588884
TI  - The basic residues of placenta growth factor type 2 retrieve sequestered
      angiogenic factors into a soluble form: implications for tumor angiogenesis.
AB  - Placenta growth factor type 1 (PIGF-1) can be synthesized by neoplastic cells in
      an alternative form (PIGF-2) by the addition of basic amino acids to its classic
      sequence. Here we show that the basic residues of PIGF-2 compete for the binding
      of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor
      (VEGF) to heparan sulfate proteoglycans of the cell surface and extracellular
      matrix. In doing so, PIGF-2 basic sequences inhibit the sequestering of VEGF and
      bFGF and maintain them in a highly diffusible form, thus enhancing their
      angiogenic effect. In agreement with these in vitro data, the presence of PIGF-2
      transcripts in tumors correlates with their blood vessel number. These results
      suggest a mechanism by which growth factor isoforms produced by neoplastic cells
      enhance the formation of new blood vessels supporting tumor growth and
      progression.

PMID- 9588886
TI  - Use of nonbreakpoint DNA probes to detect the t(X;18) in interphase cells from
      synovial sarcoma: implications for detection of diagnostic tumor translocations.
AB  - Fluorescence in situ hybridization studies using non-breakpoint DNA probes were
      performed to detect the X;18 translocation on 4-microm sections of synovial
      sarcoma from paraffin blocks. This was done by using commercially available,
      large target unique sequence DNA probes for regions of the X chromosome short-arm
      and the 18 chromosome long-arm together with centromere probes for the alternate
      chromosomes. We determined that such probe combinations could detect the presence
      of the diagnostic X;18 translocation in interphase cells. Spatial association of
      dual color signals from the X centromere and the 18 unique sequence probe, as
      well as between an 18 centromere and the X unique sequence probe, was seen in a
      significantly higher percentage of synovial sarcoma cells (81.1% +/- 7.7%,
      confidence interval 95%) than in control nonsynovial soft tissue sarcomas (14.7%
      +/- 8.3%) and control peripheral blood lymphocytes (5.6% +/- 0.6%). The observed
      spatial association supports the use of this strategy to detect the X;18
      translocation in synovial sarcoma and suggests that this technique could be
      applied in the diagnosis of other types of tumors with characteristic
      translocations when histopathological findings are inconclusive. This study is
      the first report describing the use of nonbreakpoint unique sequence probes for
      detecting translocations in tumors on paraffin-embedded slides.

PMID- 9588887
TI  - UVB induces atypical melanocytic lesions and melanoma in human skin.
AB  - A direct causal relationship between ultraviolet (UV) light in the B range and
      melanoma development has not been demonstrated in humans; this study aims to
      establish causality. A total of 158 RAG-1 mice, grafted with human newborn
      foreskin, were separated into four groups and observed for a median of 10 months:
      1) no treatment, 2) a single treatment with 7,12-dimethyl(a)benzanthracene
      (DMBA), 3) UVB irradiation at 500 J/m2 alone, three times weekly, and 4) a
      combination of DMBA and UVB. Twenty-three percent of 40 normal human skin grafts
      treated with UVB only and 38% of 48 grafts treated with the combination of DMBA
      and UVB developed solar lentigines within 5 to 10 months of treatment.
      Melanocytic hyperplasia was found in 73% of all UVB-treated xenografts.
      Histological melanocytic changes resembling lentigo and lentigo maligna were seen
      in several skin grafts treated with both DMBA and UVB. In one graft of an animal
      treated with a combination of DMBA and UVB, a human malignant melanoma, nodular
      type, developed. This experimental system demonstrates that chronic UVB
      irradiation with or without an initiating carcinogen can induce human melanocytic
      lesions, including melanoma.

PMID- 9588888
TI  - Coronary arteriosclerosis after T-cell-mediated injury in transplanted mouse
      hearts: role of interferon-gamma.
AB  - This study evaluated the contribution of acute parenchymal rejection and
      interferon (IFN)-gamma to the development of graft arterial disease (GAD) in
      totally allogeneic murine cardiac transplants. BALB/c (H-2d) hearts were
      transplanted into wild-type C57BL/6 (B6, H-2b) or B6 IFN-gamma-deficient (GKO)
      recipient mice. Assessing the role of acute parenchymal rejection in the GAD
      process involved two different immunosuppression protocols using anti-CD4 and 
      CD8 monoclonal antibodies (MAbs): virtually complete long-term immunosuppression
      (denoted as complete immunosuppression) was achieved by administering both MAbs
      6, 3, and 1 day before transplantation and weekly thereafter; in
      contradistinction, a single, early, transient episode of rejection (transient
      rejection) was attained by administering MAbs beginning 4 days after transplant
      and then at weekly intervals. The extent and duration of T cell depletion under
      these two regimens were evaluated using flow cytometric analysis of peripheral
      blood lymphocytes. After a single injection of MAbs, peripheral blood CD4+ and
      CD8+ T cell depletion was approximately 98% at 1 week and approximately 88% at 2
      weeks. After three injections (analogous to days 6, 3, and 1 before transplant),
      peripheral blood CD4+ and CD8+ T cell depletion was >98% at 2 weeks and
      approximately 87% at 4 weeks. Functioning cardiac allografts were removed at 8
      and 12 weeks after transplant and analyzed by hematoxylin and eosin, elastic
      tissue, and immunohistochemical stains, and the severity of parenchymal rejection
      versus GAD was scored. With complete immunosuppression (antibody before and after
      transplant), BALB/c allografts showed little parenchymal rejection or GAD,
      suggesting that persistent depletion of T cells blocked subsequent development of
      GAD. However, even a single transient acute rejection episode allowed the
      subsequent development of GAD accompanied by augmented major histocompatibility
      complex (MHC) class II, VCAM-1, and ICAM-1 expression at 12 weeks; these
      allografts showed no residual CD4+ or CD8+ T cells. In comparison, allografts
      undergoing transient rejection in GKO recipients did not develop GAD, despite
      persistent macrophage and natural killer cell (NK) infiltrates comparable to
      those seen in wild-type recipients. Moreover, the arterioles of hearts
      transplanted into GKO recipients showed no or minimal increases in MHC class II,
      ICAM-1, and VCAM-1 relative to baseline expression. In conclusion, a single
      episode of allogeneic injury mediated by T cells suffices to evoke subsequent
      graft arteriosclerosis, even in the absence of additional T-cell-mediated injury,
      and the process appears to depend on IFN-gamma.

PMID- 9588889
TI  - Galectin-3 expression in human atherosclerotic lesions.
AB  - The expression of galectin-3, a beta-galactoside-binding lectin, was studied in
      atherosclerotic lesions from specimens obtained from carotid endarterectomies,
      lower limb amputations, and thoracic aortas from autopsies of young adult trauma
      victims. Immunohistochemical staining with the monoclonal antibody M3/38
      demonstrated the presence of galectin-3 in advanced atherosclerotic lesions from
      each of 13 cases of carotid endarterectomy and 16 lower limb amputations and in
      the thoracic aorta of 4 of 20 cases of trauma victim adults. Immunostaining did
      not detect galectin-3 in umbilical cord and normal thoracic aorta arteries and
      limb veins. Dual immunostaining with monoclonal antibodies M3/38 for galectin-3
      and clone 1A4 for smooth muscle alpha-actin or HAM56 for human macrophage antigen
      showed that galectin-3 was localized predominantly in foam cells and macrophages
      and rarely (<5%) in the smooth muscle cells of atherosclerotic lesions. The
      incidence of galectin-3-positive cells was higher in the carotid artery
      atherosclerotic lesions, which are richer in foam cells, than in the lower limb
      atherosclerotic lesions, which are more fibrotic. Reverse transcription
      polymerase chain reaction showed a significantly higher ratio of galectin-3/beta
      actin transcripts in 20 atherosclerotic arteries compared with that of 5
      umbilical cord arteries. Western blot analysis confirmed a higher level of
      galectin-3 in atherosclerotic carotid and lower limb arteries compared with that
      of umbilical cord arteries. The increased expression of galectin-3 in
      atherosclerotic lesions suggests the involvement of this multifunctional protein
      in atherogenesis.

PMID- 9588890
TI  - Antibodies against mesangial cells and their secretory products in chronic renal
      allograft rejection in the rat.
AB  - Antibodies or cell-mediated immunity can cause chronic rejection of vascularized
      organ grafts, but the nature and specificity of the antigen(s) involved has
      remained elusive. We have previously demonstrated the presence of antibodies
      against cryptic glomerular basement membrane antigens and undefined antigens in
      the mesangial area in rats with chronic renal allograft rejection. Current
      experiments were designed to study the post-transplant antibody response against
      cultured mesangial and endothelial cells in rats with chronic rejection using
      flow cytometry, indirect immunofluorescent staining, immunoelectron microscopy,
      confocal microscopy, and Western blots. The results were compared with those
      obtained with alloantisera raised by immunization with cultured mesangial cells.
      Post-transplant and post-immunization sera contained IgG antibodies against
      trypsinized mesangial cells detected by flow cytometry. Indirect
      immunofluorescent studies using mesangial cells grown on coverslips showed
      autoantibody binding to cytoplasmic granules in cultures early after plating
      whereas staining of later cultures showed antibody binding in an interrupted, web
      like pattern on the outside of the cells. Immunoelectron microscopy showed
      autoantibody binding to intracellular secretory granules and to cell surface
      focal adhesion plaques. The latter finding was confirmed in double-labeling
      experiments with an antiserum against vinculin. Western blots with mesangial cell
      culture supernatants demonstrated autoantibody reactivity with antigens in the 40
      kd and 60- to 70-kd range, and immunoprecipitation identified these molecules as
      biglycan and decorin. Absorption of the sera with mesangial cell culture
      supernatant removed most of the antibodies except those that gave a punctate
      staining with the mesangial cell surface. However, not all immunostaining of
      mesangial cells could be explained by antibodies against biglycan and decorin.
      Post-transplant sera, furthermore, contained low-titered antibodies against
      endothelial cells. We conclude that rats with chronic renal transplant rejection
      produce a strong autoantibody response against mesangial cell focal adhesion
      plaques and proteins secreted by these cells in culture. Such antibodies may
      cause local damage and interfere in the tissue repair process after injury.

PMID- 9588891
TI  - Short-term urinary flow impairment deregulates PAX2 and PCNA expression and cell
      survival in fetal sheep kidneys.
AB  - Renal malformations account for most children with chronic renal failure and are
      often associated with urinary tract anatomical obstruction. We examined cellular
      and molecular events after experimental urinary flow impairment in fetal sheep.
      Ovine gestation lasts 144 to 150 days with the metanephros appearing at 27 to 30
      days. We generated complete unilateral ureteric anatomical obstruction at 90 days
      when a few layers of glomeruli had formed. After 10 days, we recorded ureteric
      and pelvic dilatation with renal parenchymal weight greater than contralateral
      organs or those from unoperated fetuses. The nephrogenic cortex was replaced by
      disorganized cells separated by edema and prominent vascular spaces. Cortical
      histology was dominated by cysts associated with malformed glomerular tufts.
      Cystic epithelia expressed PAX2, a growth-stimulating transcription factor down
      regulated during normal maturation, and proliferating cell nuclear antigen, a
      surrogate marker of cycling cells. Detection of apoptosis using propidium iodide
      and in situ end labeling showed a significant increase of the point prevalence of
      death in the obstructed cortex. Hence, PAX2 and proliferating cell nuclear
      antigen expression as well as death were deregulated, as we previously reported
      in human kidney malformations. Medullary collecting ducts and loops of Henle were
      also disrupted, correlating with impaired urinary dilution and sodium
      reabsorption. Therefore, complex aberrations of morphogenesis, gene expression,
      cell turnover, and urine composition occur relatively early after experimental
      impairment of fetal urinary flow.

PMID- 9588892
TI  - Tenascin-C promotes healing of Habu-snake venom-induced glomerulonephritis:
      studies in knockout congenic mice and in culture.
AB  - Mice without the gene for tenascin-C, a multifunctional extracellular matrix
      protein expressed in many important biological events, including wound healing,
      did not show any phenotype. However, it is now obvious that the phenotype of
      deletion of one gene frequently depends on the genetic background. Therefore, we
      have newly generated tenascin-C knockout mice (KO) by backcrossing original KO
      into three congenic lines: C57BL/6N, BALB/cA, and GRS/A (GR). And we investigated
      the disease course of reversible kidney injury, Habu-snake venom-induced
      proliferative glomerulonephritis. In all strains, the disease was more severe in
      KO, but the severity varied with the strain. The KO-GR showed irreversibility;
      all treated KO-GR died by the 4th month due to renal failure. The diseased KO-GR
      showed abnormal regenerative reactions, including reduced proliferation of
      mesangial cells, key players in glomerulonephritis, and reduced production of
      some kinds of cytokines and matrices, leading to poor formation of granulation
      tissue. In culture, the mesangial cells from the KO-GR had the same potential for
      proliferation and response to cytokines as controls, but interestingly, to
      achieve this potential, they required contact with tenascin-C. These reactions
      were blocked by an anti-tenascin monoclonal antibody. The results of the present
      study, the first report showing the most dramatic phenotype so far discovered,
      have strongly suggested the importance of tenascin-C in the resolution of the
      renal inflammation and that of the genetic background on which the KO was
      developed.

PMID- 9588893
TI  - Gene expression, immunolocalization, and secretion of human defensin-5 in human
      female reproductive tract.
AB  - This study describes the novel localization of the antimicrobial peptide human
      intestinal defensin-5 (HD-5) in female genital tract epithelia. Using a 3' rapid
      amplification of cDNA ends (RACE) protocol, HD-5 was cloned from a vaginal
      epithelial cell RNA preparation, and its identity was confirmed by sequencing.
      Tissue samples from multiple donors were subsequently screened for HD-5
      expression by reverse transcription polymerase chain reaction. HD-5 message was
      invariantly expressed by normal vagina and ectocervix and inflamed fallopian
      tube, but variably expressed by normal endocervix, endometrium, and fallopian
      tube (60, 64, and 29% of specimens, respectively). Expression in endometrium was
      the highest during the early secretory phase of the menstrual cycle. Using
      immunohistochemistry and confocal microscopy, HD-5 peptide was localized in the
      upper half of the stratified squamous epithelium of the vagina and ectocervix,
      with the intensity of cellular staining increasing toward the lumen. In positive
      endocervix, endometrium, and fallopian tube specimens, HD-5 was located in
      apically oriented granules and on the apical surface of a proportion of columnar
      epithelial cells. Using Western blot analysis, secreted HD-5 was detected in
      cervicovaginal lavages, with the highest concentrations found during the
      secretory phase of the menstrual cycle. We hypothesize that HD-5 is an intrinsic
      component of the female urogenital innate immune defense system and that its
      expression may be modulated by hormonal and proinflammatory factors.

PMID- 9588894
TI  - Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors
      show phenotypic characteristics of the interstitial cells of Cajal.
AB  - The interstitial cells of Cajal (ICC) form a complex cell network within the
      gastrointestinal tract wall where they function as a pacemaker system. Expression
      of the kit proto-oncogene is essential for the development of this system. The
      aim of our study was to examine the hypothesis that gastrointestinal stromal
      tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58
      stromal tumors were characterized and found to share many features with ICC.
      Seventy-eight stromal tumors were immunophenotyped, particularly with regard to
      the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for
      the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal
      hyperplasia and hypertrophy of kit receptor positive cells were also observed in
      the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed
      in interstitial cells surrounding Auerbach's ganglia suggests that a
      subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors
      were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas
      and leiomyosarcomas, were all negative for the kit receptor. We conclude that
      gastrointestinal stromal tumors show striking morphological and immunophenotypic
      similarities with ICC and that they may originate from stem cells that
      differentiate toward a pacemaker cell phenotype. We propose that the noncommittal
      name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker
      cell tumor.

PMID- 9588895
TI  - B-cell monoclonality precedes the development of gastric MALT lymphoma in
      Helicobacter pylori-associated chronic gastritis.
AB  - Little is known about the temporal changes in Helicobacter pylori density and B
      cell clonality during the evolution from chronic gastritis to gastric mucosa
      associated lymphoid tissue (MALT) lymphoma. Biopsied specimens from 28 patients
      with chronic gastritis who developed gastric MALT lymphoma (group A) and from 24
      similar patients who did not (group B) during an equivalent follow-up period
      (mean, 42 months) were retrospectively scored for histological features of MALT
      lymphoma (0 to 5) and H. pylori density (0 to 3). B-cell clonality was analyzed
      by polymerase chain reaction (PCR). During the observation period, the H. pylori
      density in group A decreased significantly in comparison with group B; the mean
      change in H. pylori density (final minus initial density) per 1000 days was -1.4
      for group A and +0.2 for group B (P < 0.005). Monoclonality was detected more
      frequently in group A (79%) than in group B (21%; P < 0.005), and it preceded the
      histological evidence of malignant transformation in 64% of those patients who
      showed monoclonality in group A. These results suggest that H. pylori is thus
      more closely associated with the precursor or initial phase in the genesis of
      gastric MALT lymphoma than with the later phase, as its density decreases as the
      tumor progresses. The detection of B-cell monoclonality by PCR is thus of
      possible use for predicting the histological genesis of gastric lymphoma.

PMID- 9588897
TI  - Nucleolar function and size in cancer cells.
AB  - We have have studied the relationship between nucleolar function and size and
      cell doubling time in cancer cells. Seven human cancer cell lines characterized
      by different proliferation rates were used. Nucleolar functional activity was
      evaluated by measuring RNA polymerase I activity and expression of RNA polymerase
      I upstream binding factor (UBF), DNA topoisomerase I, and fibrillarin, three
      proteins involved in synthesis and processing of rRNA. Transcriptional activity
      of RNA polymerase I was strictly related to cell doubling time (r = -0.97; P <
      0.001). The quantitative distribution of UBF, DNA topoisomerase I, and
      fibrillarin was evaluated on Western blots using specific monoclonal antibodies
      by densitometric analysis of autoradiographic signals. It was found to be
      directly related to RNA polymerase I transcriptional activity (r = 0.89, P =
      0.008 for UBF; r = 0.95, P = 0.001 for DNA topoisomerase I; and r = 0.91, P =
      0.004 for fibrillarin) and inversely related to cell doubling time (r = -0.87, P
      = 0.011 for UBF; r = -0.97, P < 0.001 for DNA topoisomerase I; and r = -0.91, P =
      0.005 for fibrillarin). The nucleolar areas were measured by automated image
      analysis on toluidine blue-stained cells. The values of the stained nucleolar
      structures per cell were directly related to RNA polymerase I transcriptional
      activity (r = 0.94, P = 0.001) and inversely related to cell doubling time (r = 
      0.98, P < 0.001). The same area values of the nucleolar structures stained by
      toluidine blue were also closely related to the amount of UBF (r = 0.92, P =
      0.003), DNA topoisomerase I (r = 0.98, P < 0.001), and fibrillarin (r = 0.95, P =
      0.001), and to the in situ quantitative distribution of AgNOR proteins (r = 0.98,
      P < 0.001). Our results demonstrated that in cancer cells rRNA transcriptional
      activity and nucleolar size are inversely related to cell doubling time.
      Quantitative distribution of nucleolar structures within the cell represents a
      cytohistological parameter of the rapidity of cell proliferation.

PMID- 9588896
TI  - Microsatellite instability and loss of heterozygosity in gastric carcinoma in
      comparison to family history.
AB  - We compared 29 gastric carcinomas from patients with a variably strong family
      history for gastric cancer (group 1) with 36 gastric carcinomas from patients
      without a family history of this disease (group 2) for microsatellite instability
      (MSI) and loss of heterozygosity (LOH) with 12 microsatellite markers. Both study
      groups had similar proportions of histological types and tumor locations.
      Widespread MSI (alterations at > or = 6 loci) was seen in 5 of 29 (17%) of the
      tumors belonging to group 1 and in 4 of 36 (11%) group 2 tumors. MSI at a low
      level (alterations at 1 to 3 loci) was observed in 12 of 29 (41%) of tumors in
      group 1 and in 10 of 36 (28%) of tumors in group 2, differences that were not
      statistically significant. A significant difference with respect to low level MSI
      was observed between the two groups when considering the overall mutation rate of
      microsatellites. Seventeen of 281 (6%) analyzed microsatellite loci showed
      alterations in group 1 and 11 of 381 (2.9%) in group 2 (P = 0.046). Comparison of
      both types of MSI to the clinicopathological parameters in both groups revealed a
      significant association of low level MSI with advanced tumor stages (P = 0.046)
      in the group 2, whereas no such association was observed in group 1. In respect
      to LOH, a significant difference between the two groups was observed at
      chromosome 17p12, as 13 of 22 (59%) informative cases of group 1 showed LOH in
      comparison with 7 of 26 (27%) (P = 0.024) in group 2. No correlation of LOH at
      chromosome 17p12 to the pathological or clinical data was observed either in the
      two groups or in the study as a whole. Our data show that gastric carcinomas of
      patients with a positive family history of gastric cancer in group 1 are
      characterized by a higher mutation rate in respect to low level MSI, particularly
      at dinucleotide repeats, and by a higher frequency of LOH at chromosome 17p12,
      indicating that different genetic pathways are involved in the pathogenesis of
      gastric carcinomas arising in patients with and without a familial background of
      this disease.

PMID- 9588898
TI  - Growth characteristics and metastatic properties of human breast cancer
      xenografts in immunodeficient mice.
AB  - We evaluated the growth and metastatic potential of two human breast cancer cell
      lines and 16 patient-derived biopsy specimens, representing the most common
      histological types of breast carcinomas, upon subcutaneous implantation into
      severe combined immunodeficient (SCID) mice. The method of engraftment we used,
      based on implantation of intact tissue specimens and complete immunosuppression
      of the host, provided an easier system to grow human breast carcinoma specimens
      in mouse models and resulted in a 50% success rate of tumor take. No correlation
      was found between growth in SCID mice and pathological diagnosis, grading, or
      estrogen/progesterone receptor expression by the tumor biopsy specimen. Serial
      passage of the tumor fragments in SCID mice resulted in increased metastasis
      rates and more rapid emergence of a palpable tumor mass. A tumor from a patient
      with infiltrating ductal carcinoma, which grew aggressively and metastasized in
      100% of the female SCID mice, was also successfully engrafted in 100% of nonobese
      diabetic (NOD)/SCID female mice, but systemic spread was minimal. Fragments of
      the same tumor grew in only 33% of male SCID mice with very limited metastases. A
      strong correlation (r = 0.997) was observed between tumor burden and the presence
      of soluble (serum) interleukin-2 receptor, a marker associated with a subset of
      human breast tumors. All together, these data indicate the usefulness of
      SCID/human breast tumor xenografts for measuring tumor progression and evaluating
      novel therapeutic approaches to breast cancer.

PMID- 9588899
TI  - Patterns of allelic loss (LOH) in vulvar squamous carcinomas and adjacent
      noninvasive epithelia.
AB  - The pathogenesis of carcinoma of the vulva is diverse and includes both human
      papilloma virus (HPV)-positive and HPV-negative pathways. The objective of this
      study was to correlate the morphology with patterns of loss of heterozygosity
      (LOH) within four vulvar carcinomas and in adjacent vulvar epithelia. Tumors were
      categorized as HPV positive or negative by polymerase chain reaction (PCR)
      analysis. Forty-one different sites of normal squamous mucosa, hyperplasia,
      vulvar intraepithelial neoplasia (VIN), and carcinoma were microdissected in
      duplicate, and each extracted DNA was analyzed in duplicate for LOH at 10
      chromosomal loci by PCR and polyacrylamide gel electrophoresis. Patterns of LOH
      were compared within different sites of tumors and between the tumor and the
      noninvasive epithelia. Of three tumors with multiple invasive foci analyzed,
      divergent patterns of LOH were identified in two, correlating in one with
      differences in tumor grade. In one HPV-16-positive case, multiple sites of VIN
      displayed heterogeneity for LOH consistent with divergent clonal or subclonal
      populations, some of which were not shared by the tumor. In one HPV-negative
      case, LOH was found in foci of hyperplasia and differentiated VIN (atypical
      hyperplasia), the latter sharing LOH with the invasive carcinoma at some but not
      all chromosomal loci. This study suggests that a genetic relationship exists
      between VIN and carcinoma, irrespective of HPV involvement. It also suggests that
      in HPV-negative tumors, allelic loss may predate the onset of invasive carcinoma
      and, in some cases, cellular atypia (VIN). However, the divergent patterns of LOH
      observed imply that many genetic alterations in the adjacent vulvar epithelium
      are not directly related to the invasive carcinoma.

PMID- 9588900
TI  - Spatial and temporal dynamics of hepatic stellate cell activation during oxidant
      stress-induced fibrogenesis.
AB  - In vitro and in vivo studies indicate that oxidant stress is implicated in liver
      fibrogenesis. However, it is still unknown whether, in vivo, oxidant stress
      directly affects the hepatic cells responsible for fibrogenesis, ie, the hepatic
      stellate cells (HSCs). This study was aimed at answering this question by
      assessing the temporal and spatial relationships between oxidant stress and
      activation of HSCs in an in vivo model of oxidant-stress-associated fibrogenesis.
      To this purpose, rats were treated with carbon tetrachloride (CCl4) and livers
      subjected to in situ perfusion with nitroblue tetrazolium, which, in the presence
      of superoxide ions, is reduced to an insoluble blue-colored formazan derivative
      and is readily detectable in the tissue by light microscopy. Moreover, various
      combinations of in situ hybridization and immunocytochemical analyses were
      performed. An acute dose of CCl4 caused a transient production of superoxide
      radicals at 24 hours into pericentral necrotic areas, whereas HSC appearance and
      expression of collagen mRNA were detectable only at 48 and 72 hours. After
      chronic CCl4 intoxication, higher levels of oxygen radical production in necrotic
      areas were detectable along with dramatic and sustained activation of HSCs.
      However, maximal HSC activation was still delayed as compared with superoxide
      production. Expression of heme oxygenase, a gene responsive to a variety of
      oxidant stress mediators, was strongly enhanced by chronic CCl4 administration
      but remained unchanged in HSCs, both in situ and after isolation of pure HSC
      fractions from control and CCl4-treated animals. In conclusion, during
      postnecrotic fibrogenesis, oxidant stress anticipates HSC activation. HSCs do not
      directly face an oxidant stress while engaged in active fibrogenesis.

PMID- 9588901
TI  - NF-kappaB activation during IgG immune complex-induced lung injury: requirements
      for TNF-alpha and IL-1beta but not complement.
AB  - The development of acute lung inflammatory injury induced by alveolar deposition
      of IgG immune complexes in rats requires increased production of the
      proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), and
      interleukin-1beta (IL-1beta) as well as the complement activation product, C5a.
      Transcription of TNF-alpha and IL-1beta genes are known to be regulated by the
      nuclear factor-kappa B (NF-kappaB). During IgG immune complex-induced lung
      inflammation, NF-kappaB has been shown to be activated in both alveolar
      macrophages and whole lung tissues. In the current studies we sought to determine
      whether TNF-alpha, IL-1beta, the complement system and oxidants contribute to the
      activation of NF-kappaB in the lung. Electrophoretic mobility shift analysis of
      nuclear extracts from whole lung tissues demonstrated that NF-kappaB activation
      induced by the presence of IgG immune complexes occurred independently of the
      complement system and neutrophils. Intrapulmonary instillation of TNF-alpha or IL
      1beta into normal lung induced NF-kappaB, whereas C5a was incapable of causing NF
      kappaB activation. In alveolar macrophages stimulated in vitro with IgG immune
      complexes, NF-kappaB activation was greatly attenuated in the presence of
      antibodies to TNF-alpha or IL-1beta. Similarly, in vivo blockade of TNF-alpha or
      IL-1beta suppressed lung NF-kappaB activation during IgG immune complex-induced
      lung injury. N-acetylcysteine, but not catalase, suppressed activation of lung NF
      kappaB. These data suggest that TNF-alpha and IL-1beta function in an autocrine
      or paracrine manner to amplify the lung inflammatory response through activation
      of NF-kappaB. Oxidants not derived from neutrophils also appear to play a role in
      this process, whereas complement activation products are not involved in this
      phenomenon.

PMID- 9588902
TI  - Autoimmune orchitis, epididymitis, and vasitis are immunogenetically distinct
      lesions.
AB  - Experimental allergic orchitis (EAO), the principle animal model of noninfectious
      testicular inflammatory disease, is a genetically determined phenotype. Classical
      EAO, induced by inoculation with testicular homogenate and the appropriate
      adjuvants, is characterized by inflammatory infiltrates in the testis (orchitis),
      epididymis (epididymitis), and vas deferens (vasitis). In this study, the genetic
      control of susceptibility and resistance to these three lesions was analyzed in
      the mouse. The results obtained with independent inbred strains and H2 congenic
      mice show that the genetic control of all three lesions is complex and involves
      both H2 and non-H2-linked genes. Whole-genome exclusion mapping was performed on
      a backcross population segregating for all three phenotypes. Permutation-derived
      thresholds provided experimentwise, chromosomewise, comparisonwise, and marker
      specific chromosomewise thresholds for declaration of significant regions linked
      to marker loci. Unique loci were identified on chromosome 8 for orchitis,
      chromosome 16 for epididymitis, and chromosome 1 for vasitis and have been
      designated as Orch6, Epd1, and Vas1, respectively. These results show that
      autoimmune orchitis, epididymitis, and vasitis are immunogenetically distinct
      lesions.

PMID- 9588903
TI  - Interleukin-12 promotes activation of effector cells that induce a severe
      destructive granulomatous form of murine experimental autoimmune thyroiditis.
AB  - Granulomatous inflammatory lesions are a major histopathological feature of a
      wide spectrum of human infectious and autoimmune diseases. Experimental
      autoimmune thyroiditis (EAT) with granulomatous histopathological features can be
      induced by mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro
      with MTg and anti-interleukin-2 receptor (anti-IL-2R), anti-IL-2, or anti
      interferon-gamma (anti-IFN-gamma) monoclonal antibody (MAb). These studies
      suggested that IFN-gamma-producing T cells requiring IL-2 for growth may
      negatively regulate activation of granulomatous EAT effector cells. As IL-12
      promotes activation of IFN-gamma-producing Th1 cells, the present study was
      undertaken to determine the role of IL-12 in activation of effector cells for
      granulomatous EAT. MTg-sensitized cells activated in vitro with MTg, anti-IL2R
      MAb, and IL-12 induced severe, destructive granulomatous thyroiditis with
      neutrophil inflammation, fibrin deposition, and necrosis. Many glands ultimately
      underwent atrophy and became fibrotic; some also showed fibrinoid necrosis and a
      mixed inflammatory cell infiltration of blood vessel walls indicative of a
      necrotizing vasculitis. Induction of severe granulomatous EAT by IL-12 required
      MTg in vitro and was unrelated to the IL-12-induced increase in IFN-gamma
      production. IL-12 markedly increased IFN-gamma production but did not induce a
      shift to a Th1-dominant phenotype, as other Th1 and Th2 cytokines were generally
      unaffected and both Th1 and Th2 cytokines were expressed in recipient thyroids.
      Addition of IL-12 or neutralization by anti-IL-12 at various times indicated that
      IL-12 exerted its primary effects in the final 24 hours of the 72-hour culture
      and was not required in recipient mice. Cells cultured with anti-IL-12, MTg, and
      anti-IL2R MAb transferred mild lymphocytic EAT but little or no granulomatous
      EAT. Thus, IL-12 profoundly regulates the in vitro activation of effector cells
      that induce histologically distinct autoimmune inflammatory lesions in the
      thyroid.

PMID- 9588904
TI  - The 67-kd laminin receptor is preferentially expressed by proliferating retinal
      vessels in a murine model of ischemic retinopathy.
AB  - Endothelial cell association with vascular basement membranes is complex and
      plays a critical role in regulation of cell adhesion and proliferation. The
      interaction between the membrane-associated 67-kd receptor (67LR) and the
      basement membrane protein laminin has been studied in several cell systems where
      it was shown to be crucial for adhesion and attachment during angiogenesis. As
      angiogenesis in the pathological setting of proliferative retinopathy is a major
      cause of blindness in the Western world we examined the expression of 67LR in a
      murine model of hyperoxia-induced retinopathy that exhibits retinal
      neovascularization. Mice exposed to hyperoxia for 5 days starting at postnatal
      day 7 (P7) and returned to room air (at P12) showed closure of the central
      retinal vasculature. In response to the ensuing retinal ischemia, there was
      consistent preretinal neovascularization starting around P17, which persisted
      until P21, after which the new vessels regressed. Immunohistochemistry was
      performed on these retinas using an antibody specific for 67LR. At P12,
      immunoreactivity for 67LR was absent in the retina, but by P17 it was observed in
      preretinal proliferating vessels and also within the adjacent intraretinal
      vasculature. Intraretinal 67LR immunoreactivity diminished beyond P17 until by
      P21 immunoreactivity was almost completely absent, although it persisted in the
      preretinal vasculature. Control P17 mice (not exposed to hyperoxia) failed to
      demonstrate any 67LR immunoreactivity in their retinas. Parallel in situ
      hybridization studies demonstrated 67LR gene expression in the retinal ganglion
      cells of control and hyperoxia-exposed mice. In addition, the neovascular intra-
      and preretinal vessels of hyperoxia-treated P17 and P21 mice labeled strongly for
      67LR mRNA. This study has characterized 67LR immunolocalization and gene
      expression in a murine model of ischemic retinopathy. Results suggest that,
      although the 67LR gene is expressed at high levels in the retinal ganglion cells,
      the mature receptor protein is preferentially localized to the proliferating
      retinal vasculature and is almost completely absent from quiescent vessels. The
      differential expression of 67LR between proliferating and quiescent retinal
      vessels suggests that this laminin receptor is an important and novel target for
      future chemotherapeutic intervention during proliferative vasculopathies.

PMID- 9588905
TI  - Relaxin protects against myocardial injury caused by ischemia and reperfusion in
      rat heart.
AB  - Myocardial injury caused by ischemia and reperfusion comes from multiple
      pathogenic events, including endothelial damage, neutrophil extravasation into
      tissue, platelet and mast cell activation, and peroxidation of cell membrane
      lipids, which are followed by myocardial cell alterations resulting eventually in
      cell necrosis. The current study was designed to test the possible
      cardioprotective effect of the hormone relaxin, which has been found to cause
      coronary vessel dilation and to inhibit platelet and mast cell activation.
      Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the
      left anterior descending coronary artery; reperfusion (for 60 minutes or less if
      the rats died before this predetermined time) was induced by removal of the
      ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia.
      The results obtained showed that relaxin strongly reduces 1) the extension of the
      myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular
      arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase
      activity, a marker of neutrophil accumulation, 6) production of
      malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule
      release, 8) calcium overload, and 9) morphological signs of myocardial cell
      injury. This study shows that relaxin can be regarded as an agent with a marked
      cardioprotective action against ischemia-reperfusion-induced myocardial injury.

PMID- 9588906
TI  - Rapid development of severe hyperplastic gastritis with gastric epithelial
      dedifferentiation in Helicobacter felis-infected IL-10(-/-) mice.
AB  - Interleukin (IL)-10 is a potent anti-inflammatory and immune-regulatory cytokine.
      Mice deficient in IL-10 production (IL-10(-/-)) develop a spontaneous
      inflammatory bowel disease, indicating that IL-10 is an important regulator of
      the mucosal immune response in vivo. To study the role of IL-10 in the host
      response to gastric Helicobacter infection, stomachs of IL-10(-/-) and wild-type
      mice were colonized with Helicobacter felis, as a model of human H. pylori
      infection. Within 4 weeks of H. felis infection, wild-type mice develop a mild,
      focal chronic gastritis. In contrast, H. felis-infected IL-10(-/-) mice develop a
      severe hyperplastic gastritis, characterized by a dense, predominantly
      mononuclear cell inflammation of the mucosa and submucosa and epithelial cell
      proliferation and dedifferentiation. Within 4 weeks of H. felis infection, there
      are striking alterations in the character of the gastric epithelium from IL-10(-/
      ) mice, including a profound loss of parietal and chief cells, focal de novo
      production of acidic mucins, and marked epithelial proliferation with disordered
      epithelial architecture. These findings indicate that, in the absence of IL-10,
      the inflammatory and immunological responses of the murine host to gastric
      colonization with Helicobacter is a rapidly evolving pathological process with
      features that mimic those associated with H. pylori infection in humans. H. felis
      infected IL-10(-/-) mice may provide a model with which to investigate the
      cellular and molecular changes that stem from gastric infection with H. pylori.

PMID- 9588908
TI  - Transgenic mice model of ocular neovascularization driven by vascular endothelial
      growth factor (VEGF) overexpression.

PMID- 9588907
TI  - Reduction in amyloid A amyloid formation in apolipoprotein-E-deficient mice.
AB  - Apolipoproteins have been implicated in the formation of amyloid fibrils. Recent
      studies have demonstrated that apolipoprotein E (apoE), alone or in combination
      with apolipoprotein J (apoJ), and other lipoproteins appear to enhance deposition
      of amyloid fibrils both in systemic and cerebral amyloids, especially Alzheimer's
      disease (AD). ApoE enhanced the ability of the amyloid beta-protein (1-40)
      fragment (A beta) to form fibrils in vitro, with apoE4 promoting the greatest
      fibril formation. ApoE was found associated with both human and mouse amyloid A
      (AA) deposits. To define the role of apoE in vivo, we utilized mice lacking the
      apoE gene by gene targeting. We used the AA model in mice to characterize the
      function of the apoE protein in amyloid fibrillogenesis. ApoE-deficient mice
      exhibited a decrease in deposition of AA when compared with heterozygous mutant
      or wild-type animals. In addition, apoE-deficient mice that were injected with an
      adenovirus that expressed the human apoE3 gene had restored AA deposition and the
      apoE was associated with the AA fibrils. These results are agreement with the in
      vitro studies using the beta-peptide and suggest that apoE is not essential for
      amyloid fibrillogenesis but can promote the development of amyloid deposition.

PMID- 9588909
TI  - Epstein-Barr virus (EBV) variant with a 30-bp deletion at the carboxyl terminus
      (amino acids 346-355) of latent membrane protein-1 (LMP1) gene is able to
      transform cells and evade immune surveillance.

PMID- 9588910
TI  - Possible role of glutathione in predicting radiotherapy response of cervix
      cancer.
AB  - PURPOSE: To see if changes in tumor/blood glutathione (GSH) levels after one
      fraction of radiotherapy can be correlated with the treatment response in
      patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: The study
      was done on 45 patients with squamous cell carcinoma of the uterine cervix, FIGO
      Stages IIB (17 patients) and IIIB (28 patients). Stage IIB patients received 35
      Gy of cobalt-60 external radiotherapy (RT) in 16 fractions over 4 weeks with a
      concurrent high-dose-rate intracavitary dose of 8.5 Gy to point A once a week.
      Stage IIIB patients were given 45 Gy of RT in 20 fractions over 5 weeks, followed
      by two doses of intracavitary therapy once a week. Blood and tumor samples were
      collected before and after one dose of RT and GSH was estimated. Tumor response
      was assessed clinically at 1 month after treatment. RESULTS: Glutathione levels
      in both blood and tumor showed a significant decrease after one fraction of RT,
      but the degree of decrease varied among patients. There was a good correlation
      between the extent of GSH decrease and the tumor response. All patients who had
      complete response (CR) (seven Stage IIB and eight Stage IIIB) showed > or =70%
      decrease in both tumor and blood GSH, while those who had <50% regression (NR)
      (five Stage IIB and 13 Stage IIIB) showed <50% decrease in GSH. The partial
      responders recorded an intermediate level (50-70%) of depletion in blood and
      tumor GSH. CONCLUSIONS: The results indicate that the changes in tumor/blood GSH
      levels after one fraction of RT could serve as an index of tumor response to
      therapy and may help in identifying radioresistant tumors, at least in the case
      of cervix carcinoma.

PMID- 9588911
TI  - Radiation therapy for endometrial cancer in patients treated for postoperative
      recurrence.
AB  - PURPOSE: To retrospectively evaluate the outcome and risk factors in patients
      treated with radiation for endometrial cancer at time of recurrence. MATERIALS
      AND METHODS: Three hundred ninety-nine women were treated with radiation therapy
      for endometrial cancer at KCI/WSU from January 1980 to December 1994. Of these,
      26 patients treated primarily with surgery received radiation therapy at the time
      of recurrence. Median time to recurrence after surgery was 8 months, with all
      recurrences occurring within 24 months. Twenty-four patients had recurrences in
      the vaginal cuff, vagina, or pelvis. These patients received external-beam
      radiation to the pelvis (45.00-50.40 Gy) and periaortic lymph nodes (45.00-50.00
      Gy), along with a boost given by external-beam radiation or brachytherapy (16.00
      30.00 Gy). Mean follow-up was 15 months (range 1-85 months). RESULTS: The 2-year
      survival was 50% and median survival was 16 months (survival range 1-85 months).
      Of 26 patients, 54% (14) failed locally following radiation therapy. Factors
      indicative of poor survival included histology (sarcoma, poorly differentiated
      adenocarcinoma), grade, and lymph node positivity. Histological differentiation
      influenced local control; lymphovascular space invasion was of borderline
      significance with regard to local control. CONCLUSION: Local control and survival
      for surgically treated endometrial cancer patients who receive radiation at the
      time of recurrence are poor, with the exception of those patients with recurrent
      disease limited to the vagina. Early detection of recurrence may improve outcome.
      Pathologic risk factors may identify those patients at risk for extrapelvic
      recurrence. Alternative treatment modalities need to be developed for this high
      risk group of patients.

PMID- 9588912
TI  - Spatial reproducibility of the ring and tandem high-dose rate cervix applicator.
AB  - PURPOSE: High-dose rate (HDR) applicators for uterine cervix brachytherapy are
      used with increasing frequency. Because multiple HDR fractions are required for
      treatment, the applicator position reproducibility is of most importance. To
      study this effect, the clinical data from patients with uterine cervix cancer
      were examined retrospectively to evaluate the interfraction geometric variation
      of the HDR applicator and its potential treatment impact. METHODS AND MATERIALS:
      Eighteen patients with invasive cervical cancer who were treated with definitive
      radiotherapy at William Beaumont Hospital were included in the study. Patients
      were treated with 45-50.4 Gy megavoltage external beam to the pelvis, and 35 Gy
      to the prescription point A from 7 fractions of HDR brachytherapy. The 3
      dimensional (3D) interfraction geometrical variation of the ring and tandem (R &
      T) applicator was measured using predefined reference points in the 7 sets of
      orthogonal simulation films obtained prior to each HDR application. Spatial
      reproducibility of the R & T insertion and time-trend of the R & T position
      variation related to patient's anatomy during the treatment course were analyzed
      with respect to different groups of patients who had either early or advanced
      disease. RESULTS: The translational variation of the applicator position for all
      patients was 6.5, 5.9, and 7.7 mm (one standard deviation), respectively, in the
      patient's superior-to-inferior (SI), right-to-left lateral (RL), and anterior-to
      posterior (AP) direction. The rotational variation was 3.4, 4.6, and 6.0 degrees
      (one standard deviation) in the patient's coronal, transverse, and sagittal
      planes. When the patients were grouped based on early disease or advanced
      disease, the latter demonstrated substantially larger variation (factor of 2) in
      the applicator position than the former. Furthermore, the time-trend of position
      variation was observable for both groups of patients. The variations occurred
      primarily during the first 3 fractions. CONCLUSIONS: Based on the good spatial
      reproducibility observed in our study, the current clinical procedure for the HDR
      R & T applicator placement is reliable. Positional reproducibility of the R & T
      applicator is highly dependent upon the size of tumor volume, which, in turn,
      deviates the applicator during the early course of HDR brachytherapy. Attention
      to the construction of the midline block is of paramount importance.

PMID- 9588913
TI  - Treatment systems guidelines for primary rectal cancer from the 1996 Patterns of
      Care Study.
AB  - PURPOSE: The Patterns of Care Rectal Cancer Committee was formed to develop
      consensus recommendations for patients with adenocarcinoma of the rectum limited
      to the pelvis. METHODS AND MATERIALS: The Committee was composed of a
      multidisciplinary group of oncologists, and clinical scenarios were chosen to
      address most of the major treatment controversies in the combined modality
      treatment of rectal cancer. A literature search was then conducted and the major
      articles were identified. A modified Delphi technique was used to arrive at
      consensus. Serial surveys were conducted by distributing questionnaires to the
      Committee members to consolidate expert opinion. Voting was conducted using a
      scoring system and opinions were unified to the highest degree possible. RESULTS:
      Consensus voting was performed for 4 clinical scenarios. Acceptability ratings
      for treatment were grouped into 3 broad categories: not acceptable, acceptable,
      and most acceptable. Based on the treatment options, a decision tree was
      developed that reflects the consensus of the committee. CONCLUSION: These options
      may help guide treatment decisions in rectal cancer.

PMID- 9588914
TI  - The prognostic significance of p53 expression for survival and local control in
      rectal carcinoma treated with surgery and postoperative radiotherapy.
AB  - PURPOSE: To investigate whether p53 immunoreactivity is a prognostic factor for
      survival and pelvic control in rectal carcinoma treated with surgery and
      postoperative radiotherapy. METHODS AND MATERIALS: From 1981 through 1989, 146
      patients with rectal carcinoma received postoperative radiotherapy and were
      followed for at least 5 years or until death. The specimens of 123 of these 146
      patients could be retrieved and examined immunohistochemically for p53
      expression. The prognostic value for survival and pelvic control of p53
      expression and other patient and treatment factors was examined by univariate and
      multivariate analyses. RESULTS: p53 expression has no prognostic significance for
      overall survival in this group of 123 patients. The only prognostic factor for
      survival in this material is tumor stage (p < 0.01). The actuarial pelvic
      recurrence rates of p53- and p53+ cases are different in favor of the p53- ones.
      In the univariate analysis this difference is significant (p = 0.05). However, in
      the multivariate analysis the influence of p53 expression, additional to stage,
      becomes nonsignificant (p = 0.10). This indicates that p53 expression is not a
      strong independent prognostic factor for pelvic recurrence. In the multivariate
      analysis stage turns out to be the only predictor of pelvic recurrence (p =
      0.03). When only recurrences inside the radiation field are considered, there is
      no difference between p53+ and p53-cases. CONCLUSION: Based on this material, we
      have found no convincing evidence that p53 expression is an important predictor
      of survival or local control in rectal cancer treated with surgery and
      postoperative radiotherapy. We have found no evidence that possible differences
      in radiosensitivity between p53+ and p53- tumors have clinical significance for
      this group of patients.

PMID- 9588915
TI  - Overexpression of p53 protein does not predict local-regional control or survival
      in patients with early-stage squamous cell carcinoma of the glottic larynx
      treated with radiotherapy.
AB  - PURPOSE: Nonfunctional or mutated p53 protein (m-p53) is found in a myriad of
      solid tumors in humans. m-p53 is believed to confer radioresistance through
      inhibition of radiation-induced apoptosis. This study was carried out to
      determine if the overexpression of p53 in squamous cell carcinomas (SCC) of the
      glottic larynx treated with radiation therapy alone carried a poorer prognosis
      than normal wild-type p53 (w-p53) and could, therefore, be used as a marker of
      radioresistance in glottic SCC. METHODS & MATERIALS: Eighty-six patients with
      early-stage glottic SCC (64 T1N0, 25 T2N0 by TMN stage) treated with contemporary
      radiotherapy techniques to doses of 50-70 Gy were analyzed. Aberrant p53 protein
      was detected by immunohistochemical (IHC) staining on archival tissue samples
      containing original tumor specimens. Analysis of prognostic factors and treatment
      outcome to expression of p53 was performed. All patients were carefully selected
      to have comparable sites of disease, histology, early-stage disease, and
      treatment delivered, thus increasing the power of this study by controlling for
      other independent factors affecting outcome. RESULTS: Sixty percent of patients
      demonstrated overexpression of p53 in tissue samples. Accumulation of p53 was not
      predictive of tumor grade, stage, or smoking status prior to diagnosis. p53
      status was not predictive of treatment outcome parameters including local
      regional failure rate and disease-free survival rate. Factors significantly
      affecting treatment outcome were stage and dose of radiotherapy in T2 patients
      (50 Gy vs. > 62 Gy). CONCLUSION: m-p53 protein detected by IHC staining was not
      predictive as a prognostic factor for clinical outcome following radiation
      therapy for early-stage glottic SCC. This is in general agreement with other
      recently published studies of laryngeal carcinoma patients treated with radiation
      or surgery. At the present time, p53 status should not be used as a marker for
      prognosis and clinical outcome in laryngeal SCC.

PMID- 9588916
TI  - The prognostic significance of tracheostomy in carcinoma of the larynx treated
      with radiotherapy and surgery for salvage.
AB  - PURPOSE: To determine retrospectively the prognostic significance of airway
      compromise necessitating tracheostomy in carcinoma of the larynx managed with
      radical radiotherapy and surgery for salvage (RRSS). METHODS AND MATERIALS: The
      charts of 270 patients managed with RRSS at the Toronto-Sunnybrook Regional
      Cancer Centre between June 1980 and December 1990 were reviewed. Airway
      compromise necessitating tracheostomy was documented in 26 patients prior to
      radiotherapy and 3 patients during radiotherapy. Of 29, 27 had T3T4 primaries.
      Patients have been followed for a median of 5 years. RESULTS: Patients managed
      without tracheostomy had a 2-year disease-free survival of 74% compared to 41%
      for those managed with tracheostomy. The adverse impact of airway compromise was
      more marked in patients with glottic primaries (78% vs. 32%, p = 0.0001) than
      those with supraglottic primaries (64% vs. 47%, p = 0.18). Tracheostomy was
      identified in univariate analysis, but not in multivariate analysis, as having a
      statistically significant impact on local control and local-regional control.
      Radiotherapy controlled disease above the clavicles in 185 of 267 (69%) evaluable
      patients. 83% of isolated local-regional failures underwent salvage surgery.
      Among those managed without tracheostomy, ultimate local-regional control (LRC)
      was achieved in 161 (94%) of 172 glottic primaries and 54 (81%) of 67
      supraglottic primaries. Among those managed with tracheostomy, ultimate LRC was
      achieved in 9 (69%) of 13 glottic primaries and 12 (80%) of 15 supraglottic
      primaries. In a subset analysis of 76 patients with T3T4 primaries, there was no
      statistically significant difference in larynx preservation, disease-free
      survival, or cause-specific survival between those managed with and without
      tracheostomy. CONCLUSION: Airway compromise necessitating tracheostomy is an
      adverse prognostic factor in patients with carcinoma of the larynx. However,
      larynx preservation is possible in over 40% of those undergoing tracheostomy and
      radiotherapy with no compromise of cause-specific survival. The need for
      pretreatment tracheostomy should not rule out the possibility of RRSS.

PMID- 9588917
TI  - High dose rate versus low dose rate interstitial radiotherapy for carcinoma of
      the floor of mouth.
AB  - PURPOSE: Patients with cancer of the floor of mouth are treated with radiation
      because of functional and cosmetic reasons. We evaluate the treatment results of
      high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of
      the floor of mouth. METHODS AND MATERIALS: From January 1980 through March 1996,
      41 patients with cancer of the floor of mouth were treated with LDR interstitial
      radiation using 198Au grains, and from April 1992 through March 1996 16 patients
      with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3
      tumor. For 21 patients treated with interstitial radiation alone, a total
      radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and
      85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a
      total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8
      fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. RESULTS:
      Two- and 5-year local control rates of patients treated with HDR interstitial
      radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively.
      Local control rate of patients treated with HDR brachytherapy was slightly higher
      than that with 198Au grains (p = 0.113). For late complication, bone exposure or
      ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%)
      patients treated with LDR. CONCLUSION: HDR fractionated interstitial
      brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor
      of mouth and eliminate radiation exposure for the medical staff.

PMID- 9588918
TI  - Temporal lobe (TL) damage following surgery and high-dose photon and proton
      irradiation in 96 patients affected by chordomas and chondrosarcomas of the base
      of the skull.
AB  - PURPOSE: To determine the temporal lobe (TL) damage rate in 96 patients treated
      with high-dose proton and photon irradiation for chordomas and chondrosarcomas of
      the base of the skull. METHODS AND MATERIALS: The records of 96 consecutive
      patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron
      Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of
      the base of the skull were reviewed. All the patients had undergone some degree
      of resection of the tumor prior to radiation therapy. Seventy-five patients were
      classified as "primary tumors" and 21 as recurrent or regrowing tumors after one
      or more surgical procedures. All the patients were randomized to receive 66.6 or
      72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton
      and photon irradiation (Radiation Therapy Oncology Group #85-26) with
      conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were
      planned using the three-dimensional (3D) planning system developed at the
      Massachusetts General Hospital, and the dose was delivered using opposed lateral
      fields for the photon component and a noncoplanar isocentric technique for the
      proton component. Clinical symptoms of TL damage were classified into 4 grades.
      Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were
      evaluated for white matter changes. Abnormalities associated with persistent or
      recurrent tumor were distinguished from radiation-induced changes. TLs were
      delineated on the original scans of the 10 patients with damage and those of a
      group of 33 patients with no clinical or MRI evidence of injury. Dose
      distributions were calculated and dose-volume histograms were obtained for these
      patients. RESULTS: Of the patients, 10 developed TL damage, with bilateral injury
      in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5
      years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were
      always separated from the tumor bed. Symptoms were severe to moderate in 8
      patients. Several baseline factors, tumor- or host-related, were analyzed to
      evaluate their predictivity for TL damage: age, gender, tumor site, histology,
      type of presentation, type and number of surgical procedures, primary tumor
      volume, prescribed dose, normal tissue involvement, and volume of TL receiving
      doses ranging between 10 and 50 CGE or more. Only gender, in a univariate
      analysis (log rank) was a significant predictor of damage (0.0155), with male
      patients being at significantly higher risk of TL injury. In a stepwise Cox
      regression that included gender as a variable, no other baseline variable
      improved the prediction of damage. CONCLUSIONS: The 2- and 5-year cumulative TL
      damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage
      rates related to age, tumor volume, number of surgical procedures prior to
      radiation therapy, and prescribed doses to the tumor, only gender was a
      significant predictor of damage (p = 0.0155) using a univariate (log rank) test.
      Chordomas and chondrosarcomas of the base of the skull may represent an
      interesting model to evaluate the TL damage rates because of their extradural
      origin, displacing the white matter instead of infiltrating it as gliomas do,
      because of their longer local recurrence-free survival other than gliomas and
      other brain tumors and because of the high doses of irradiation delivered to the
      target volume to obtain local control.

PMID- 9588919
TI  - Use of a general inverse technique for the conformational stereotactic treatment
      of complex intracranial lesions.
AB  - PURPOSE: The stereotactic irradiation of intracranial lesions constitutes an
      excellent example of conformational therapy whose purpose is to adapt the dose
      envelope to the target volume with great precision and at the same time to
      deliver as low a dose as possible to the healthy tissues. We propose the
      mathematical analysis of the singular values decomposition (SVD) as an inverse
      planning process to find the optimal minibeam weightings that permit the
      calculation of the most conformational dose distribution. METHODS: For the
      radiosurgical treatment of complex lesions, we realize a division of the lesion
      into several elliptic volumes using the "Associated Target Methodology." This
      division allows the definition of an irradiation configuration: the number of
      isocenters, the position of the isocenters, and the diameter of each collimator.
      For this defined irradiation configuration, we use SVD to find the optimal
      minibeam weightings. This analysis enables us to understand better the ill
      conditioning of the multi-isocentric irradiation and the influence of irradiation
      parameters on the process of reconstruction minibeam weightings. RESULTS: In this
      paper, the SVD analysis and the reconstruction technique have been evaluated for
      the first time on practical cases. We present, as an example, a complex lesion
      compartmentalized into 3 subvolumes according to our Associated Target
      Methodology. This analysis allows us to study the ill-conditioning of the example
      and proposes a large number of solutions from among which we have to choose the
      most conformational physical solution. This choice is based on the dose-volume
      histograms. CONCLUSION: We use the SVD procedure as a computer-aided planning
      system and obtain good solutions, i.e., healthy tissue protection and lesion
      coverage similar to or better than an experimented planner solution.

PMID- 9588920
TI  - The use of 3D conformal radiotherapy (3D CRT) to spare the cochlea in patients
      with medulloblastoma.
AB  - PURPOSE: Radiation therapy in combination with cis-platinum chemotherapy is
      associated with ototoxicity due to destruction of cochlear hair cells. This is a
      significant problem, especially in pediatric patients, because it may lead to
      difficulties with communication, speech, language, and development of learning
      skills. The use of 3D conformal radiotherapy (3D CRT) may be useful in sparing
      auditory structures. This paper discusses a technique using 3D CRT to spare the
      cochlea in patients with medulloblastoma. METHODS AND MATERIALS: Five pediatric
      patients with medulloblastoma were planned using 3D CRT. All had MRI and CT
      obtained specifically for treatment planning. Multiple structures were contoured,
      including the cochlea and posterior fossa, and conformal beams designed in beam's
      eye view and dose distribution analysis were edited to provide 3D dose coverage
      to the target while sparing the inner ear. Patients received 36 Gy to the
      craniospinal axis followed by an 18-20 Gy boost to the posterior fossa. RESULTS:
      A 3D CRT cochlear sparing technique was designed, using an axial pair of
      posterior oblique fields to treat the posterior fossa while sparing the cochlea
      for all patients in this analysis. Dose-volume information, obtained from 3D
      calculations, demonstrates that the average dose received by the cochlea was 65%
      of the prescribed dose using the cochlear sparing plan, as compared to 101% using
      standard opposed-lateral beams. Both plans delivered > or = 100% of the
      prescribed dose to the posterior fossa. CONCLUSION: 3D CRT allows for cochlear
      sparing in the treatment of medulloblastoma. Further follow-up is necessary to
      determine the long-term benefit in these patients.

PMID- 9588921
TI  - Estimation of the incidence of late bladder and rectum complications after high
      dose (70-78 GY) conformal radiotherapy for prostate cancer, using dose-volume
      histograms.
AB  - PURPOSE: To investigate whether Dose-Volume Histogram (DVH) parameters can be
      used to identify risk groups for developing late gastrointestinal (GI) and
      genitourinary (GU) complications after conformal radiotherapy for prostate
      cancer. METHODS AND MATERIALS: DVH parameters were analyzed for 130 patients with
      localized prostate cancer, treated with conformal radiotherapy in a dose
      escalating protocol (70-78 Gy, 2 Gy per fraction). The incidence of late (>6
      months) GI and GU complications was classified using the RTOG/EORTC and the
      SOMA/LENT scoring system. In addition, GI complications were divided in nonsevere
      and severe (requiring one or more laser treatments or blood transfusions) rectal
      bleeding. The median follow-up time was 24 months. We investigated whether rectal
      and bladder wall volumes, irradiated to various dose levels, correlated with the
      observed actuarial incidences of GI and GU complications, using volume as a
      continuous variable. Subsequently, for each dose level in the DVH, the rectal
      wall volumes were dichotomized using different volumes as cutoff levels. The
      impact of the total radiation dose, and the maximum radiation dose in the rectal
      and bladder wall was analyzed as well. RESULTS: The actuarial incidence at 2
      years for GI complications > or =Grade II was 14% (RTOG/EORTC) or 20%
      (SOMA/LENT); for GU complications > or =Grade III 8% (RTOG/EORTC) or 21%
      (SOMA/LENT). Neither for GI complications > or =Grade II (RTOG/EORTC or
      SOMA/LENT), nor for GU complications > or =Grade III (RTOG/EORTC or SOMA/LENT),
      was a significant correlation found between any of the DVH parameters and the
      actuarial incidence of complications. For severe rectal bleeding (actuarial
      incidence at 2 years 3%), four consecutive volume cutoff levels were found, which
      significantly discriminated between high and low risk. A trend was observed that
      a total radiation dose > or = 74 Gy (or a maximum radiation dose in the rectal
      wall >75 Gy) resulted in a higher incidence of severe rectal bleeding (p = 0.07).
      CONCLUSIONS: These data show that dose escalation up to 78 Gy, using a conformal
      technique, is feasible. However, these data have also demonstrated that the
      incidence of severe late rectal bleeding is increased above certain dose-volume
      thresholds.

PMID- 9588922
TI  - Neutron beam radiotherapy for recurrent prostate cancer following radical
      prostatectomy.
AB  - PURPOSE: To evaluate the effectiveness of neutron beam radiotherapy (NXRT) to
      treat recurrent prostate cancer following radical prostatectomy (RP). METHODS AND
      MATERIALS: Twenty-five patients who failed RP received NXRT at our institution.
      The pathological stages ranged from T2c-T3c, with 16 patients having either
      seminal vesicle involvement and/or nodal metastases. Sixteen patients also
      received neoadjuvant hormones. Freedom from relapse (FFR) was defined by an
      undetectable PSA (PSA < or =0.2). Median follow-up was 27 months, with no
      patients lost to follow-up. RESULTS: Postneutron PSA became initially
      undetectable in 84% of patients. The actuarial FFR is 36% at 3 years. Nine
      patients remain NED, 12 patients have an elevated PSA only, 2 patients have
      clinical recurrence, and 2 patients are dead of prostate cancer. Pre-NXRT PSA
      levels of < or =1.0 vs. >1.0 predicted for outcome, with a FFR at 3 years of 76
      vs. 14% (p = 0.003). Patients with a persistently elevated PSA following RP were
      not effectively salvaged by NXRT, with a 12% FFR at 3 years compared to a 62% FFR
      for patients whose PSA initially normalized following RP (p = 0.03). There was no
      difference in treatment outcomes based on fields encompassing pelvic nodes vs.
      fields directed to the prostatic fossa only. There were no severe (RTOG Grade 3)
      late complications. CONCLUSION: NXRT is an effective salvage treatment for
      carefully selected patients. This group includes patients whose PSA initially
      normalized following RP, and whose pre-NXRT PSA < or =1.0.

PMID- 9588923
TI  - A dose-response study for I-125 prostate implants.
AB  - PURPOSE: No dose-response study has ever been performed for I-125 prostate
      implants using modern techniques of implant evaluation and modern treatment
      outcome end points. The amount of activity per volume implanted was increased
      over time based on review of postimplant dosimetry. This resulted in different
      delivered dose levels. This study explores the relationship between dose,
      biochemical failure, and biopsy results. MATERIALS AND METHODS: 134 patients with
      T1-T2 prostate cancer were implanted with I-125 radioactive seeds and followed
      from 12 to 74 months (median: 32) postimplant. No patient received external beam
      irradiation or hormonal therapy. All patients implanted with I-125 had Gleason
      scores < or =6. One month postimplant, a CT-based three-dimensional dosimetric
      evaluation was performed on all patients. Using TG43 guidelines, dose-volume
      histograms were calculated. The dose delivered to the gland was defined as the
      D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged
      from 26.8 to 256.3 Gy (median: 140.8 Gy). Biochemical failure was defined as two
      consecutive rises in prostate specific antigen (PSA) or a nadir level above 1.0
      ng/ml. Posttreatment prostate biopsies (six to eight core samples) were routinely
      performed at 2 years postimplant. RESULTS: Improvements in freedom from
      biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year
      FFBF rates for patients with D90 values < 100 Gy, 100-119.9 Gy, 120-13.9 Gy, 140
      159.9 Gy, and > or =160 Gy were 53, 82, 80, 95, and 89%, respectively (p = 0.02).
      Patients receiving a D90 < 140 Gy (65 patients) were similar with respect to
      presenting disease prognostic factors to those receiving a D90 > or =140 Gy (69
      patients). Patients receiving a D90 < 140 Gy had a 4-year FFBF rate of 68%
      compared to a rate of 92% for those receiving a D90 > or =140 Gy (p = 0.02). Two
      year posttreatment biopsies were negative in 70% (33 of 47) of patients with a
      D90 < 140 Gy compared to a rate of 83% (24 of 29) in patients with a D90 > or
      =140 Gy (p = 0.2). A multivariate analysis using dose, PSA, score, and stage
      revealed that dose was the most significant predictor of biochemical failure (p =
      0.001). This dose response was more pronounced in patients presenting with PSA
      levels > 10 ng/ml. In these patients, the 4-year FFBF rates were 51 and 100% for
      the low and high dose groups, respectively (p = 0.009) and the negative biopsy
      rates were 64% (14 of 22) and 100% (8 of 8), respectively (p = 0.05). In patients
      with presenting PSA <10 ng/ml, the 4-year FFBF rates were 82 and 88% for the low
      and high dose groups, respectively (p = 0.29). CONCLUSION: A dose response was
      observed at a level of 140 Gy. Adequate I-125 implants should deliver a dose of
      140-160 Gy using TG43 guidelines.

PMID- 9588924
TI  - Predictors of delay in starting radiation treatment for patients with early stage
      breast cancer.
AB  - PURPOSE: To describe the factors predicting waiting time for radiation treatment
      in early breast cancer. MATERIALS AND METHODS: Between January 1992 and December
      1993, 739 patients with Stage I and II breast cancer were treated with
      conservative treatment at three McGill University Hospitals. Waiting time was
      defined as the interval between the date of surgery and the date of the first
      radiation treatment. Delay was defined as a waiting time of more than 7 weeks for
      women who did not receive chemotherapy (Group NC, n = 478), and as a waiting time
      of more than 24 weeks for those who received chemotherapy (Group C, n = 261). We
      analyzed predictive factors related to the patient (age, stage, treatment on
      protocol, income by postal code) and to the referring hospital (university or
      community hospital). RESULTS: For the entire population, 54% of patients were
      delayed, 72% in Group NC and 21.4% in Group C. Univariate analysis showed an
      impact of referring hospital in both groups, and of stage and treatment on
      protocol in Group C (all p = 0.001). Multivariate analysis showed that delays
      were significantly less in Group NC for women referred from a community hospital
      (p = 0.001) and in Group C for women with Stage I disease (p = 0.06), those
      treated on protocol, and those referred from a university hospital (p = 0.001).
      CONCLUSION: More than half of patients with early breast cancer waited more than
      the recommended intervals for radiation therapy. However, lower income breast
      cancer patients did not wait longer for treatment than higher income patients,
      possibly a result of the Canadian Medicare system which provides universal access
      to health care.

PMID- 9588925
TI  - Long-term results of total abdominopelvic irradiation in non-Hodgkin's lymphomas
      after failure of chemotherapy.
AB  - PURPOSE: To evaluate the therapeutic efficacy of moderate-dose total
      abdominopelvic irradiation (TAI) in a retrospective series of pretreated non
      Hodgkin's lymphomas (NHL). METHODS AND MATERIALS: From 1977 to 1994, 45 patients
      received TAI after failure of chemotherapy (CT). According to the Working
      Formulation, 10 patients were diagnosed with class A (group I), 19 with class B,
      C, or D (follicular) (group II), and 16 with class E or more severe (group III)
      NHL. Irradiation consisted of two daily fractions of 0.80 Gy each for a total
      dose of 20 Gy. RESULTS: Mean follow-up after TAI was 102 months (range 8-156).
      For the entire group, the complete response (CR) rate was 66%, the partial
      response (PR) rate 29%, 10-year overall survival (OS) 35%, 10-year disease-free
      survival (DFS) 29%, and median survival 32 months. When results between subgroups
      were compared, CR was 70% in group I, 84% in group II, and 44% in group III; and
      survival was statistically higher in group II than in groups I and III: 10-year
      OS 52% vs. 10% (p < 0.01) and 31% (p < 0.05), respectively, 10-year DFS 37% vs.
      10% (p < 0.03) and 19% (p < 0.05), respectively. Grade III or IV complications
      were gastrointestinal in 27% of patients and hematologic in 25%. CONCLUSION:
      Large-field irradiation in moderate doses could provide an alternative to bone
      marrow transplantation in refractory NHL, especially in cases showing a
      follicular growth pattern.

PMID- 9588926
TI  - Low-dose splenic irradiation in the treatment of immune thrombocytopenia in HIV
      infected patients.
AB  - PURPOSE: To determine the effect of low-dose splenic irradiation on severe
      Zidovudine-resistant, HIV-1-associated thrombocytopenia (HAT). METHODS AND
      MATERIALS: Between September 1994 and October 1996, 17 patients were included in
      a prospective study. The patients met the following criteria for inclusion:
      hemorrhagic symptoms or a platelet count below or equal to 50 x 10(9)/l and
      normal numbers of megakaryocytes on bone aspiration. The mean baseline platelet
      count was 20.3 (+/- 14.4) x 10(9)/l; four patients had a platelet count inferior
      to 10 x 10(9)/l. Splenic volume was defined by ultrasonography. A total dose of 9
      Gy was given using an isocentric parallel pair field technique. RESULTS: One
      month after the end of treatment six patients had a significant rise in their
      platelet count. Clinically, hemorrhagic symptoms stopped for all patients that
      were symptomatic. Unfortunately, duration of response was short because for one
      patient only the platelet count remains stable with a follow-up of 6 months. All
      patients are alive and in recent evaluation, with four out of eight patients
      receiving a combination of antiretroviral therapy had a platelet count above 50 x
      10(9)/l. CONCLUSION: Our results are disappointing concerning the duration of
      response, especially comparatively to those reported in autoimmune
      thrombocytopenia. Mechanisms of HAT are more complex, and megakaryocytes'
      infection may play an important role. Splenic irradiation should be considered as
      palliative treatment for the minority of patients with severe bleeding that does
      not respond to standard medical treatment.

PMID- 9588927
TI  - Current status of radioactive stents for the prevention of in-stent restenosis.
AB  - PURPOSE: The objective of this paper was to provide an update on the clinical and
      experimental evaluation of radioactive stents for the prevention of restenosis.
      MATERIALS AND METHODS: Direct ion implantation of 32P onto the surface of a 15-mm
      length balloon expandable stainless-steel Palmaz-Schatz stent was employed to
      render this commercially available vascular stent radioactive. 32Phosphorous, a
      pure beta-particle-emitting radioisotope, was selected because of its short half
      life (14.3 days) and limited range of tissue penetration (3-4 mm). The vascular
      response to radioactive 7-mm length Palmaz-Schatz stents with activities 0.14 to
      23 microCi of 32P were evaluated in animal models of arterial injury and
      restenosis. The Phase-1 isostent for restenosis intervention study (IRIS trial)
      was a nonrandomized safety trial designed to evaluate the use of a low activity
      32P (0.5 to 1.5 microCi) 15-mm length Palmaz-Schatz stent for the treatment of de
      novo or restenosis native coronary arterial lesions. RESULTS: In the porcine
      coronary restenosis model, at < or =0.5 microCi and > or =3.0 microCi stent
      activities, there was a 30% reduction in the neointimal and percent area stenosis
      as compared to nonradioactive stents. The 1.0 microCi stents, however, had nearly
      2-fold greater neointimal formation and more luminal narrowing than the control
      stents. In the Phase 1 IRIS trial, 57 patients with symptomatic de novo or
      restenosis native coronary lesions have been treated with low activity (0.5 to
      1.5 microCi) 32P Palmaz-Schatz coronary stents. Fifty-seven stents were
      successfully implanted without a major procedural complication (death, urgent
      coronary bypass, Q-wave myocardial infarction). There were no cases of stent
      thrombosis, target vessel revascularization, or other adverse events in the first
      30 days after implant. CONCLUSION: The early clinical results with a low-activity
      32P Palmaz-Schatz radioactive stent demonstrate sufficient procedural and 30-day
      event-free survival to warrant consideration of additional clinical studies to
      determine the safety and efficacy of this therapy for the prevention of
      restenosis. Future studies will focus on optimal stent design for delivery of
      radiation, and will further evaluate safe and effective dosing strategies.

PMID- 9588928
TI  - Sublethal damage repair times for a late-responding tissue relevant to
      brachytherapy (and external-beam radiotherapy): implications for new
      brachytherapy protocols.
AB  - PURPOSE: Data were analyzed from recent experiments with the end point of late
      rectal obstruction in rats, involving acute and various protracted radiation
      exposures. Because the end point is of direct relevance both for brachytherapy as
      well as external beam radiotherapy, the goal was to estimate the linear-quadratic
      (LQ) parameters alpha/beta and T1/2, which are of importance for designing
      improved protraction/fractionation schemes. METHODS AND MATERIALS: The data were
      fit to the LQ model, both in its standard form and in a form in which two
      different components of sublethal damage repair-fast and slow-are assumed. The
      design of the experiments was such that both slow and reasonably fast sublethal
      damage repair components should be separately estimated, if they were
      contributing to a significant degree. RESULTS: LQ parameter estimates were
      alpha/beta = 4.6 Gy [4.0, 5.5] and T1/2 = 70.2 min [59.1, 91.4]. Despite the
      experimental design facilitating detection of a rapid component of repair, no
      statistically robust evidence for a very fast repair component was found.
      CONCLUSIONS: The long estimated repair time for a late-responding normal-tissue
      end point with direct relevance to brachytherapy suggests a variety of possible
      brachytherapy protocols that may be more efficacious than continuous low dose
      rate irradiation. Just as a difference in alpha/beta ratios between early- and
      late-responding tissues are a central tenet in radiotherapy, so corresponding
      differences in T1/2 values have the potential to be exploited, particularly for
      brachytherapy.

PMID- 9588929
TI  - Pulse frequency in pulsed brachytherapy based on tissue repair kinetics.
AB  - PURPOSE: Investigation of normal tissue sparing in pulsed brachytherapy (PB)
      relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse
      frequency based on tissue repair characteristics. METHOD: Using the linear
      quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated
      for tissue with an alpha/beta ratio ranging from 2 to 10 Gy and a half-time of
      sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be
      delivered either in a number of pulses varying from 2 to 25, or continuously at a
      dose rate of 0.50, 0.80, or 1.20 Gy/h. RESULTS: The RE of 20 Gy was found to be
      identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h
      for any alpha/beta value and for a repair half-time > 0.75 h. When normal tissue
      repair half-times are assumed to be longer than tumor repair half-times, normal
      tissue sparing can be obtained, within the restriction of a fixed overall
      treatment time, with higher dose per pulse and longer period time (time elapsed
      between start of pulse n and start of pulse n + 1). An optimum relative normal
      tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence,
      a therapeutic gain might be obtained when changing from CLDR to PB by adjusting
      the physical dose in such a way that the biological dose on the tumor is
      maintained. The normal tissue-sparing phenomenon can be explained by an increase
      in RE with longer period time for tissue with high alpha/beta ratio and fast or
      intermediate repair half-time, and the RE for tissue with low alpha/beta ratio
      and long repair half-time remains almost constant. CONCLUSION: Within the
      benchmark of the LQ model, advantage in normal tissue-sparing is expected when
      matching the pulse frequency to the repair kinetics of the normal tissue exposed.
      A period time longer than 1 h may lead to a reduction of late normal tissue
      complications. This theoretical advantage emphasizes the need for better
      knowledge of human tissue-repair kinetics.

PMID- 9588930
TI  - Correlation of magnetic resonance and oxygen microelectrode measurements of
      carbogen-induced changes in tumor oxygenation.
AB  - PURPOSE: The aim of this work was to test the hypothesis that decreases in the
      linewidth of magnetic resonance (MR) water signals in tumors caused by
      oxygenating treatments are due to increases in capillary and venous oxygen
      saturation of hemoglobin, which are tightly coupled to increases in extravascular
      oxygen tension (pO2). To establish this link, changes measured by MR were
      compared to changes in tissue pO2 measured directly by oxygen microelectrodes
      during carbogen (95% O2/5% CO2) inhalation. METHODS AND MATERIALS: Mammary
      adenocarcinomas (R3230AC) in nine rats were imaged at 4.7 Tesla. T1-weighted (TR
      = 200 ms, flip angle = 45 degrees) spectroscopic images of the water resonance in
      a single slice through each tumor were acquired with spectral resolution of 3.9
      Hz and bandwidth of +/-1000 Hz. In the same slices in these tumors,
      microelectrode measurements were made using a non-Clark style oxygen electrode
      with a 350-micron tip. MR and microelectrode measurements were made during
      alternating periods of air and carbogen inhalation. RESULTS: Water resonance
      linewidth decreased significantly during carbogen-induced hyperoxia. Paired
      Student's t-test analysis of microelectrode data indicated that pO2 was
      significantly (p < 0.05) increased as a result of carbogen inhalation. MR and
      microelectrode data averaged over each tumor demonstrated that decreased MR water
      signal linewidth is strongly correlated (r = 0.92, p < 0.05) with increased tumor
      pO2 levels. CONCLUSION: Although tumor oxygenating agents increase response to
      radiation in rodent tumors, clinical studies have shown only marginal effects on
      the radiosensitivity of human tumors. This may be, in part, because the effects
      of tumor oxygenating treatments are highly heterogeneous both within each tumor
      and among a population of tumors. The noninvasive, high-resolution MR methods
      that are validated by the present work could guide the design of new and more
      effective tumor oxygenating agents and optimize treatments for individual
      patients.

PMID- 9588931
TI  - Regional tumor oximetry: 19F NMR spectroscopy of hexafluorobenzene.
AB  - PURPOSE: An accurate method for monitoring oxygen tension (pO2) of individual
      tumors could be valuable for optimizing treatment plans. We have recently shown
      that 19F nuclear magnetic resonance (NMR) spin-lattice relaxometry of
      hexafluorobenzene (HFB) provides a highly sensitive indicator of tumor
      oxygenation. We have now refined the methodology to provide enhanced precision,
      and applied the method to investigate dynamic changes in tumor oxygenation.
      METHODS AND MATERIALS: Dunning prostate adenocarcinoma R3327-AT1 was grown in the
      form of pedicles on the foreback of male Copenhagen rats. When the tumors reached
      approximately equal to 1 cm diameter, HFB (20 microl) was administered, either
      centrally or peripherally, by direct intratumoral (i.T) injection. Local pO2 was
      determined using pulse-burst saturation recovery (PBSR) 19F NMR spectroscopy on
      the basis of the spin-lattice relaxation rate, R1. RESULTS: Interrogation of the
      central region of tumors provided typical values in the range pO2 = 1.4-6.4 mmHg,
      with a typical stability of +/-2 mmHg over a period of 20 min, when rats breathed
      33% O2. Altering the inhaled gas to oxygen or carbogen (95% O2/5% CO2) produced
      no significant change. In contrast, interrogation of tumor periphery indicated
      baseline pO2 in the range 7.9-78.9 mmHg. Altering inspired gas produced
      significant changes (p < 0.0001) with O2 or carbogen, although the change was
      generally greater with carbogen. In each case, pO2 returned to baseline within 16
      min of returning the inhaled gas to baseline. CONCLUSION: We believe this method
      provides a valuable new approach with the requisite precision and accuracy to
      investigate tumor pO2.

PMID- 9588932
TI  - A medical expert system approach using artificial neural networks for
      standardized treatment planning.
AB  - PURPOSE: Many radiotherapy treatment plans involve some level of standardization
      (e.g., in terms of beam ballistics, collimator settings, and wedge angles), which
      is determined primarily by tumor site and stage. If patient-to-patient variations
      in the size and shape of relevant anatomical structures for a given treatment
      site are adequately sampled, then it would seem possible to develop a general
      method for automatically mapping individual patient anatomy to a corresponding
      set of treatment variables. A medical expert system approach to standardized
      treatment planning was developed that should lead to improved planning efficiency
      and consistency. METHODS AND MATERIALS: The expert system was designed to specify
      treatment variables for new patients based upon a set of templates (a database of
      treatment plans for previous patients) and a similarity metric for determining
      the goodness of fit between the relevant anatomy of new patients and patients in
      the database. A set of artificial neural networks was used to optimize the
      treatment variables to the individual patient. A simplified example, a four-field
      box technique for prostate treatments based upon a single external contour, was
      used to test the viability of the approach. RESULTS: For a group of new prostate
      patients, treatment variables specified by the expert system were compared to
      treatment variables chosen by the dosimetrists. Performance criteria included
      dose uniformity within the target region and dose to surrounding critical organs.
      For this standardized prostate technique, a database consisting of approximately
      75 patient records was required for the expert system performance to approach
      that of the dosimetrists. CONCLUSIONS: An expert system approach to standardized
      treatment planning has the potential of improving the overall efficiency of the
      planning process by reducing the number of iterations required to generate an
      optimized dose distribution, and to function most effectively, should be closely
      integrated with a dosimetric based treatment planning system.

PMID- 9588933
TI  - Treatment planning optimization for linear accelerator radiosurgery.
AB  - PURPOSE: Linear accelerator radiosurgery uses multiple arcs delivered through
      circular collimators to produce a nominally spherical dose distribution.
      Production of dose distributions that conform to irregular lesions or conformally
      avoid critical neural structures requires a detailed understanding of the
      available treatment planning parameters. METHODS AND MATERIALS: Treatment
      planning parameters that may be manipulated within a single isocenter to provide
      conformal avoidance and dose conformation to ellipsoidal lesions include
      differential arc weighting and gantry start/stop angles. More irregular lesions
      require the use of multiple isocenters. Iterative manipulation of treatment
      planning variables can be difficult and computationally expensive, especially if
      the effects of these manipulations are not well defined. Effects of treatment
      parameter manipulation are explained and illustrated. This is followed by
      description of the University of Florida Stereotactic Radiosurgery Treatment
      Planning Algorithm. This algorithm organizes the manipulations into a practical
      approach for radiosurgery treatment planning. RESULTS: Iterative treatment
      planning parameters may be efficiently manipulated to achieve optimal treatment
      plans by following the University of Florida Treatment Planning Algorithm. The
      ability to produce conformal stereotactic treatment plans using the algorithm is
      demonstrated for a variety of clinical presentations. CONCLUSION: The standard
      dose distribution produced in linear accelerator radiosurgery is spherical, but
      manipulation of available treatment planning parameters may result in optimal
      dose conformation. The University of Florida Treatment Planning Algorithm
      organizes available treatment parameters to efficiently produce conformal
      radiosurgery treatment plans.

PMID- 9588934
TI  - Frame slippage verification in stereotactic radiosurgery.
AB  - PURPOSE: To develop a method for detecting frame slippage in stereotactic
      radiosurgery by interactively matching in three dimensions Digitally
      Reconstructed Radiographs (DRRs) to portal images. METHODS AND MATERIALS: DRRs
      are superimposed over orthogonal edge-detected portal image pairs obtained prior
      to treatment. By interactively manipulating the CT data in three dimensions
      (rotations and translations) new DRRs are generated and overlaid with the
      orthogonal portal images. This method of matching is able to account for
      ambiguities due to rotations and translations outside of the imaging plane. The
      matching procedure is performed with anatomical structures, and is used in tandem
      with a fiducial marker array attached to the stereotactic frame. The method is
      evaluated using portal images simulated from patient CT data and then tested
      using a radiographic head phantom. RESULTS: For simulation tests a mean radial
      alignment error of 0.82 mm was obtained with the 3D matching method compared to a
      mean error of 3.52 mm when using conventional matching techniques. For the head
      phantom tests the mean alignment displacement error for each of the stereotactic
      coordinates was found to be delta(x) = 0.95 mm, delta(y) = 1.06 mm, delta(z) =
      0.99 mm, with a mean error radial of 1.94 mm (SD = 0.61 mm). CONCLUSION: Results
      indicate that the accuracy of the system is appropriate for stereotactic
      radiosurgery, and is therefore an effective tool for verification of frame
      slippage.

PMID- 9588935
TI  - National radioactivity standards for beta-emitting radionuclides used in
      intravascular brachytherapy.
AB  - The uses of beta-particle emitting radionuclides in therapeutic medicine are
      rapidly expanding. To ensure the accurate assays of these nuclides prior to
      administration, radioactivity standards are needed. The National Institute of
      Standards and Technology (NIST), the national metrological standards laboratory
      for the United States, uses high-efficiency liquid scintillation counting to
      standardize solutions of such beta emitters, including 32P, 90Sr/90Y, and 188Re.
      Additional measurements are made on radionuclidic impurities, half lives, and
      other decay-scheme parameters (such as branching decay ratios or gamma-ray
      abundances) using HPGe detectors and reentrant ionization chambers. Following
      such measurements at NIST, standards are disseminated in three ways: Standard
      Reference Materials (SRMs), calibrations for source manufacturers, and
      calibration factors for commercial instruments. Uncertainties in the activity
      calibrations for these nuclides are of the order of +/-0.5% (at approximately 1
      standard deviation confidence intervals).

PMID- 9588936
TI  - Quality assurance calibration of 125I rapid strand in a sterile environment.
AB  - PURPOSE: 125I seeds encased in stiffened absorbable suture material, commercially
      available from Amersham Healthcare as 125I Rapid Strand, are not readily
      calibrated because of the necessity of maintaining the sterility and integrity of
      the Rapid Strand. A method is proposed to verify the activity of 125I seeds in
      Rapid Strand in a sterile environment and to provide quality assurance of the
      resultant loading by autoradiographing loaded needles. METHODS AND MATERIALS: A
      sterilizable insert for a Standard Imaging HDR 1000 Plus well chamber was
      designed to accommodate Amersham's plastic spacing jig that holds the strand. The
      insert has a cylindrical lead sleeve allowing five of the 10 seeds in the jig to
      be exposed within the well chamber. A grooved tray for holding a batch of 30
      needles was designed for autoradiographing the implant set. RESULTS: Position
      dependent calibration factors for each of the seed wells in the jig were
      determined; then these individual factors were combined into a single chamber
      factor of 21.6 pA/mCi. Starting from the most distal spacing jig slot, relative
      position factors were 0.99, 1.00, 0.99, 0.93, 0.73, and 0.13 for the six
      positions which produced a nonnegligible signal. Anisotropy in the chamber factor
      was determined by rotating the well in 30 degrees increments about the seeds in
      the jig. The chamber factor showed only a 0.2% variation with rotational angle.
      Attenuation due to the Vicryl suture cladding material was 0.2% and was measured
      by stripping the Vicryl from the strand and remeasuring the chamber factor with
      the seeds in their original orientation. In the operating room, charge was
      collected from sterile Rapid Strands for a fixed time between 30 and 50 s and the
      measured ion chamber current was compared with the value predicted from
      Amersham's nominal activity. The average deviation between nominal and measured
      activity of 73 Rapid Strands tested was +0.5% +/- 2.2%. For single measurements,
      the maximum and minimum deviations observed were +4.8% and -3.7%, respectively.
      Autoradiographs taken of the entire implant set on an aluminum tray milled to
      hold the needles confirmed the actual seed loadings. CONCLUSIONS: The Rapid
      Strand calibration procedure described maintains the sterility and integrity of
      125I Rapid Strands and verifies that the manufacturer's stated activity is
      accurate to within 5%.

PMID- 9588937
TI  - The doses received by the breast during mantle radiotherapy.
AB  - PURPOSE: To accurately measure the dose received by the breast during mantle
      radiotherapy. METHODS AND MATERIALS: A phantom containing lung-equivalent
      material was used to measure the doses received by the breast during mantle
      radiotherapy given by anterior and posterior opposing fields. These were measured
      using thermoluminescent dosimeters and compared with point dose calculations
      obtained by computer planning. RESULTS: Most of the breast lies under the lung
      shields or inferior to the mantle field, but the upper outer quadrant of the
      breast remains unshielded. In the unshielded areas of the breast, the average
      dose measured was nearly 13% higher than the dose prescribed at the central axis.
      In the shielded parts of the breast, the average measured dose was nearly 10% of
      the dose prescribed at the central axes, decreasing from 18% superiorly to 4%
      inferiorly. The posterior field contributed 45% to the dose in the breast, even
      though doses were prescribed at the midplane. The computer calculations
      systematically varied from measured doses by up to 35%, becoming less accurate
      towards the inferior edge of the field. CONCLUSIONS: In a conventional course of
      mantle radiotherapy (for example, 36 Gy in 20 fractions), most of the breast is
      shielded but will receive a dose of 3-4 Gy, higher than expected largely due to
      internally scattered radiation passing through the lungs from the posterior
      field. Computer dose calculations may poorly reflect actual off-axis doses in
      large fields with complex shielding, containing inhomogeneous tissue.

PMID- 9588938
TI  - Junctioning of lateral and anterior fields in head and neck cancer: a dosimetric
      assessment of the monoisocentric technique (including reproducibility).
AB  - PURPOSE: The matching or junctioning of two lateral fields with an anterior field
      is commonly performed in the treatment of head and neck cancer. A monoisocentric
      technique utilising asymmetric collimation is potentially associated with
      improved dosimetry in the plane of the junction due to decreased reliance on
      operator skill and the avoidance of couch movement. The aim of this study was not
      only to assess the average dose delivered in the plane of the junction, but also
      the reproducibility of this dose for the monoisocentric technique and two other
      commonly used techniques. METHODS AND MATERIALS: An anthropomorphic head and neck
      wax phantom was fashioned to allow the placement of 22 TLD chips in a 2-mm thick
      transverse plane positioned superior to the potential site of the larynx. Three
      different treatment techniques were used with the phantom being treated by four
      different operators a minimum of 20 times for each technique: (1) "straight
      fields"--using isocentric laterals with an anterior field junctioned in the
      midline. This technique makes no allowance for divergence; (2) "angled fields"-
      couch and gantry rotation are used to account for divergence; (3)
      "monoisocentric"--using asymmetric collimators to create a single isocenter.
      RESULTS: For an applied dose of 1 Gy the monoisocentric technique produced a mean
      dose measured of 1.01 Gy compared with 1.23 and 0.92 Gy for techniques 1 and 2.
      The reproducibility of the mean dose measured was better for the monoisocentric
      technique by a factor of 2. The superior reproducibility of the monoisocentric
      technique was not found to be operator dependent. CONCLUSIONS: A monoisocentric
      technique for the treatment of two laterals and an anterior field in head and
      neck cancer is likely to be associated with more accurate and reproducible
      dosimetry in the plane of the junction. Our center has subsequently adopted this
      technique for matching such fields.

PMID- 9588939
TI  - Evaluation of eye shields made of tungsten and aluminum in high-energy electron
      beams.
AB  - PURPOSE: To protect the lens and cornea of the eye when treating the eyelid with
      electrons, we designed a tungsten and aluminum eye shield that protected both the
      lens and cornea, and also limited the amount of backscatter to the overlying
      eyelid when using electron beam therapy. METHODS AND MATERIALS: Custom curved
      tungsten eye shields, 2 mm and 3 mm thick, were placed on Kodak XV film on 8 cm
      polystyrene and irradiated to evaluate the transmission through the shields. To
      simulate the thickness of the eyelid and to hold the micro-TLDs, an aquaplast
      mold was made to match the curvature of the eye shields. Backscatter was measured
      by placing the micro-TLDs on the beam entrance side to check the dose to the
      underside of the eyelid. Measurements were done with no aluminum, 0.5, and 1.0 mm
      of aluminum on top of the tungsten eye shields. The measurements were repeated
      with 2- and 3-mm flat pieces of lead to determine both the transmission and the
      backscatter dose for this material. RESULTS: Tungsten proved to be superior to
      lead for shielding the underlying structures and for reducing backscatter. At 6
      MeV, a 3-mm flat slab of tungsten plus 0.5 mm of aluminum, resulted in .042 Gy
      under the shield when 1.00 Gy is delivered to dmax. At 6 MeV for a 3-mm lead plus
      0.5-mm aluminum, .046 Gy was measured beneath the shield, a 9.5% decrease with
      the tungsten. Backscatter was also decreased from 1.17 to 1.13 Gy, a 4% decrease,
      when using tungsten plus 0.5 mm of aluminum vs. the same thickness of lead.
      Measurements using 9 MeV were performed in the same manner. With 3 mm tungsten
      and 0.5 mm of aluminum, at 3 mm depth the dose was .048 Gy compared to .079 Gy
      with lead and aluminum (39% decrease). Additionally, the backscatter dose was 3%
      less using tungsten. Simulating the lens dose 3 mm beyond the shield for the 2-mm
      and 3-mm custom curved tungsten eye shields plus 0.5 mm of aluminum was .030 and
      .024 Gy, respectively, using 6 MeV (20% decrease). Using 9-MeV electrons, the
      dose 3 mm beyond the shield was .048 Gy for the 2-mm shield and .029 Gy for the 3
      mm shield (40% decrease). Backscatter was not further decreased using thicker
      tungsten. With a 6-MeV beam, using the 2-mm or 3-mm custom tungsten eye shields
      plus 0.5 mm of aluminum, the backscattered doses were 1.03 and 1.02 Gy,
      respectively. The backscatter dose with 9 MeV was 1.06 Gy using the 2-mm custom
      shield plus 0.5 mm aluminum and 1.05 Gy with a 3-mm custom shield plus 0.5 mm
      aluminum. There was very little difference in backscatter dosage under the eyelid
      using 0.5 vs. 1.0 mm of aluminum. Therefore, for patient comfort, we recommend
      using 0.5 mm of aluminum. CONCLUSIONS: Tungsten is superior to lead as a material
      for eye shields due to its higher density and lower atomic number (Z). Using 6-
      and 9-MeV electrons, tungsten provides the necessary protection for the lens and
      cornea of the eye and decreases the amount of backscatter to the eyelid above the
      shield.

PMID- 9588940
TI  - Optimized dose distribution of a high dose rate vaginal cylinder.
AB  - PURPOSE: To present a comparison of optimized dose distributions for a set of
      high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment
      planning system with benchmark calculations using Monte-Carlo-calculated
      dosimetry data. METHODS AND MATERIALS: Optimized dose distributions using both an
      isotropic and an anisotropic dose calculation model were obtained for a set of
      HDR vaginal cylinders. Mathematical optimization techniques available in the
      computer treatment-planning system were used to calculate dwell times and
      positions. These dose distributions were compared with benchmark calculations
      with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times
      and positions were used for a quantitative comparison of dose calculated with
      three dose models. RESULTS: The isotropic dose calculation model can result in
      discrepancies as high as 50%. The anisotropic dose calculation model compared
      better with benchmark calculations. The differences were more significant at the
      apex of the vaginal cylinder, which is typically used as the prescription point.
      CONCLUSION: Dose calculation models available in a computer treatment-planning
      system must be evaluated carefully to ensure their correct application. It should
      also be noted that when optimized dose distribution at a distance from the
      cylinder surface is calculated using an accurate dose calculation model, the
      vaginal mucosa dose becomes significantly higher, and therefore should be
      carefully monitored.

PMID- 9588941
TI  - Hydrogen ion equilibria of Cajanus cajan lectin.
AB  - Hydrogen ion titration of an affinity-purified mannose/glucose-specific lectin
      from Cajanus cajan pulse was carried out at 30 degrees C and ionic strength of
      0.15 by a discontinuous method. The titration was reversible in the pH range 2
      12.0. The numbers of different ionizable groups per 39,000 g of the lectin were
      43 carboxyl groups (pKint = 3.93), 10 imidazole groups, 21 epsilon-amino groups,
      12.8 phenoxyl groups (pKint = 10.0), and 5 guanidyl groups. Only seven tyrosine
      residues of the lectin were dissociated under native conditions. The remaining
      six tyrosines became available for titration upon denaturation of the lectin in 9
      M urea.

PMID- 9588942
TI  - Status of Cys residues in the covalent structure of botulinum neurotoxin types A,
      B, and E.
AB  - Clostridium botulinum neurotoxin (NT) serotypes A, B, and E have 9, 10, and 8 Cys
      residues, respectively, as deduced from nucleotide sequences [Whelan et al.
      (1992), Appl. Environ. Microbiol. 48, 2345-2354]. Each of the 150-kDa NTs has at
      least one disulfide; but type B, like types A and E, may have two disulfides.
      Using two different chemical reagents, we studied the status of the Cys residues
      in these three proteins after (i) the final anion exchange chromatographic step
      in their purification (fresh NT), (ii) 24 hr storage at 8 degrees C, (iii)
      precipitation with ammonium sulfate (precipitated NT), and (iv) dissolving the
      precipitated NT in 6 M guanidine HCl. In all three NT serotypes the number of Cys
      residues titrated with 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) as free -SH
      groups varied, depending upon the absence or presence of EDTA added to the
      chromatography buffer, storage condition, age, and presence of the denaturant.
      Titration of 9.5-10 and 5.4-6.0 -SH groups in fresh NTs type B and E,
      respectively, indicated total and partial absence of disulfide bonds. Fewer
      titratable -SH groups in the precipitated NT than in the fresh NT suggested
      formation of disulfide and/or inaccessibility of the -SH groups due to protein's
      conformational change(s). When the precipitated NTs were dissolved in 6 M
      guanidine HCl, in the absence of any added reducing agent, all Cys residues of
      types B and E, and 6.4-8.3 Cys in type A NT were titratable with DTNB.
      Iodoacetamide modification of precipitated NT types A, B, and E carboxymethylated
      4, 2, and 2 Cys residues, respectively; these numbers rose to 6, 9.4, and 8 when
      these proteins were carboxymethylated after dissolving in 6 M guanidine HCl in
      the absence of any added reducing agent. We propose that S-S- cleavage mediated
      by the -SH/-S-S- exchange observed in vitro after unfolding the NTs (also
      unfolded by 2 M guanidine HCl or urea) possibly mimicks a similar exchange
      process inside the endosomes, where the NTs are thought to undergo conformational
      changes, resulting in the reductive cleavage of the interchain disulfide between
      the 50-kDa light and 100-kDa heavy chain, which in turn releases the light chain
      and allows its egress out of the endosomes into the cytosol.

PMID- 9588943
TI  - Thrombin specificity: further evidence for the importance of the beta-insertion
      loop and Trp96. Implications of the hydrophobic interaction between Trp96 and
      Pro60B Pro60C for the activity of thrombin.
AB  - A number of thrombin mutants have been constructed to investigate the role of
      Trp96 and the beta-insertion loop for the specificity of thrombin. Thrombin(60D)
      consists of the replacement of the beta-insertion loop (14 amino acid residues
      from 59 to 63, including a 9-residue insertion at position 60) with the
      corresponding four residues in trypsin, Tyr-Lys-Ser-Gly; thrombin(GGG) is a
      smaller loop mutation in which the residues Tyr(60A)Pro(60B)Pro(60C)Trp(60D)
      Asp(60E)Lys(60F) of the beta-insertion loop were replaced by Gly-Gly-Gly;
      thrombin(96S) consists of a point mutation Trp96 --> Ser; and thrombin(GGG/96S)
      is the double mutant incorporating both changes. Thrombin(96S) clots fibrinogen
      approximately 3 times more slowly than thrombin, with the two beta-insertion loop
      mutants, thrombin(GGG) and thrombin(GGG/96S), reacting approximately 3000- and
      1300-fold more slowly, respectively. The specificity constant kcat/Km for the
      cleavage of fibrinopeptide A and fibrinopeptide B by thrombin(96S) was 2.6 and
      0.35 microM(-1) s(-1), respectively, compared to 10 and 2.5 microM(-1) s(-1) for
      wild-type recombinant thrombin, respectively. Kinetic constants were determined
      for the hydrolysis of H-D-phenylalanyl-L-pipecolyl-L-arginine-p-nitroaniline. The
      Michaelis constant Km increased approximately 6-fold for thrombin(96S) and >200
      fold for thrombin(GGG) and thrombin(GGG/96S) when compared to wild-type
      recombinant thrombin, while the catalytic constant kcat remained approximately
      the same. All mutants were more susceptible to inhibition by BPTI than wild-type
      recombinant thrombin. Clearly, the beta-insertion loop is important for thrombin
      activity. But the mutation of Trp96 --> Ser can compensate somewhat for the loss
      of binding at the beta-insertion loop. The deletion of the hydrophobic
      interaction between Trp96 and Pro(60B)Pro(60C) appears to decrease the stability
      of the beta-insertion loop, thereby causing a decrease in binding efficiency.

PMID- 9588944
TI  - Prediction of protein structural classes by modified mahalanobis discriminant
      algorithm.
AB  - We first discuss quantitative rules for determining the protein structural
      classes based on their secondary structures. Then we propose a modification of
      the least Mahalanobis distance method for prediction of protein classes. It is a
      generalization of a quadratic discriminant function to the case of degenerate
      covariance matrices. The resubstitution tests and leave-one-out tests are carried
      out to compare several methods. When the class sample sizes or the covariance
      matrices of different classes are significantly different, the modified method
      should be used to replace the least Mahalanobis distance method. Two lemmas for
      the derivation of our new algorithm are proved in an appendix.

PMID- 9588945
TI  - The effect of Ser 128 substitution on the structure and stability of cAMP
      receptor protein from Escherichia coli.
AB  - Kinetic measurements of denaturation and renaturation of two mutants of cAMP
      receptor protein (CRP) at position 128, namely Ser --> Ala and Ser --> Pro, were
      performed in order to assess changes introduced by the mutation in the quaternary
      structure and protein stability. No significant changes were found in the
      unfolding/refolding reactions. However, small perturbations in the dissociation
      of CRP dimer can be seen, which indicate that subunit interactions are influenced
      by the mutation. Studies of intrinsic fluorescence quenching of these two mutants
      are also reported, showing changes compared with wild-type protein. Near-UV
      circular dichroism measurements indicate, however, that Trp residues remain in
      the same environment as in the wild-type CRP. It is proposed that Ser at position
      128 is involved in maintaining the proper domain alignment within CRP subunits.

PMID- 9588946
TI  - Catalytically active monomers of E. coli glyceraldehyde-3-phosphate
      dehydrogenase.
AB  - Monomeric forms of E. coli glyceraldehyde-3-phosphate dehydrogenase have been
      prepared using two different experimental approaches: (1) covalent immobilization
      of a tetramer on a solid support via a single subunit with subsequent
      dissociation of non-covalently bound subunits in the presence of urea, and (2)
      entrapment of monomeric species into reversed micelles of Aerosol OT in octane.
      Isolated monomers were shown to be catalytically active, exhibiting KM values
      close to the parameters characteristic of the tetrameric forms. Like tetramers,
      isolated monomers did not use NADP7 as a coenzyme.

PMID- 9588947
TI  - Secondary force-mediated perturbations of antifluorescein monoclonal antibodies 4
      4-20 and 9-40 as determined by circular dichroism.
AB  - Secondary forces have been defined as those interactions between antibody and
      antigen that occur external to the antibody active site. Previous investigations
      indicated that non-active-site secondary interactions can modulate immune complex
      stability and may influence antibody variable domain conformation and/or
      dynamics. To assess secondary force-induced perturbations of monoclonal
      antibodies 4-4-20 and 9-40 a series of monofluoresceinated peptides was reacted
      and the various interactions analyzed by circular dichroism (CD). The mAbs 4-4-20
      and 9-40 vary by nearly 1000-fold in their respective affinities for the
      fluorescein ligand, yet both immunoglobulins are highly related at the primary
      structural (idiotype) level. Near-UV CD spectra were evaluated as well as the
      induced optical activity (visible CD) of the antibody-bound fluorescein moiety
      when covalently attached to various peptide carriers. Comparative spectral
      studies revealed significant differences in the near-UV CD spectra of mAbs 9-40
      and 4-4-20 relative to the various peptide antigens and to one another. CD
      spectra were interpreted as reflecting differential secondary force-induced
      perturbations of the antibody variable domains as well as intrinsic differences
      between the two mAbs.

PMID- 9588948
TI  - Single-chain Fv of anti-idiotype 11-1G10 antibody interacts with antibody NC41
      single-chain Fv with a higher affinity than the affinity for the interaction of
      the parent Fab fragments.
AB  - A single-chain Fv (scFv) fragment of anti-idiotype antibody 11-1G10, which
      recognizes an idiotope of anti-neuraminidase antibody NC41, was constructed by
      joining VH and VL domains with a (Gly4Ser)3 linker, with a pelB leader sequence,
      and two C-terminal FLAG tag sequences, and expressed in E. coli (10 mg/L). The 11
      1G10 scFv was isolated by affinity chromatography on an anti-FLAG M2 antibody
      column as a 2:1 mixture of monomer and dimer forms which were separated by
      Superdex 75 chromatography; monomer (at 100 microg/ml) was stable for 7 days at
      21 degrees C and 30 days at 4 degrees C, whereas the dimer slowly dissociated to
      monomer to yield a 2:1 monomerdimer equilibrium mixture after 30 days at 4
      degrees C. The dimer was bivalent, with each combining site binding an NC41 Fab
      to yield a stable complex of Mr approximately 156,000. Binding affinities,
      determined in solution using a BIAcore biosensor, showed that the affinity for
      the interaction of 11-IG10 scFv monomer with NC41 scFv monomer was five- to six
      fold higher than the interaction of the parent Fab pair. This is the first
      example of an scFv derived from a monoclonal antibody with a higher affinity than
      its parent Fab.

PMID- 9588949
TI  - Coordination of nitric oxide by heme-hemopexin.
AB  - Hemopexin, which acts as an antioxidant by binding heme (Kd < 1 pM), is
      synthesized by hepatic parenchymal cells, by neurons of the central and
      peripheral nervous systems, and by human retinal ganglia. Two key regulatory
      molecules, nitric oxide (.NO) and carbon monoxide (CO), both bind to heme
      proteins and since ferroheme-hemopexin binds CO, the possible role of heme
      hemopexin in binding .NO was investigated. .NO binds rapidly to hemopexin-bound
      ferroheme as shown by characteristic changes in the Soret and visible-region
      absorbance spectra. Circular dichroism spectra of .NO-ferroheme-hemopexin in the
      Soret region exhibit an unusual bisignate feature with a zero crossover at the
      absorbance wavelength maximum, showing that exciton coupling is occurring.
      Notably, the .NO complex of ferroheme-hemopexin is sufficiently avid and stable
      to allow hemopexin to bind this molecule in vivo and, thus, hemopexin may protect
      against NO-mediated toxicity especially in conditions of trauma and hemolysis.

PMID- 9588950
TI  - Prediction of the secondary structure contents of globular proteins based on
      three structural classes.
AB  - The prediction of the secondary structural contents (those of alpha-helix and
      beta-strand) of a globular protein is of great use in the prediction of protein
      structure. In this paper, a new prediction algorithm has been proposed based on
      Chou's database [Chou (1995), Proteins 21, 319-344]. The new algorithm is an
      improved multiple linear regression method, taking into account the nonlinear and
      coupling terms of the frequencies of different amino acids and the length of the
      protein. The prediction is also based on the structural classes of proteins, but
      instead of four classes, only three classes are considered, the alpha class, beta
      class, and the mixed alpha+beta and alpha/beta class or simply the alphabeta
      class. Thus the ambiguity that usually occurs between alpha+beta proteins and
      alpha/beta proteins is eliminated. A resubstitution examination for the algorithm
      shows that the average absolute errors are 0.040 and 0.035 for the prediction of
      alpha-helix content and beta-strand content, respectively. An examination of
      cross-validation, the jackknife analysis, shows that the average absolute errors
      are 0.051 and 0.045 for the prediction of alpha-helix content and beta-strand
      content, respectively. Both examinations indicate the self-consistency and the
      extrapolating effectiveness of the new algorithm. Compared with other methods,
      ours has the merits of simplicity and convenience for use, as well as high
      prediction accuracy. By incorporating the prediction of the structural classes,
      the only input of our method is the amino acid composition and the length of the
      protein to be predicted.

PMID- 9588951
TI  - A catalytic antibody that accelerates the hydrolysis of carbonate esters.
      Prediction of the binding-site structure of the substrate.
AB  - Monoclonal antibodies catalyzing the hydrolysis of p-nitrophenyl alkyl carbonate
      were obtained using p-nitrophenyl phosphonate as hapten. One of the antibodies,
      4A1, has a relatively high activity for the substrate having a bulky group. To
      determine the amino acid residues related to the binding of the bulky group, we
      determined the amino acid sequences of VL and VH regions of 4A1 by the cycle
      sequencing method, built the three-dimensional structure of the V regions,
      labeled 4A1 with [14C]phenyl glyoxal in the presence and absence of I-1 or I-13,
      and analyzed the labeled incubation mixture with SDS-PAGE. From these results,
      the possibility that Arg-H28 of the heavy chain is involved in binding the bulky
      group of the substrate is discussed.

PMID- 9588952
TI  - Covalent fixation of soluble derivatized dextrans to model proteins in low
      concentration medium: application to factor IX and protein C.
AB  - Factor IX and protein C are zymogens implicated in blood clotting, and an
      increase in their plasmatic residence time would be of interest for the treatment
      of the disorders caused by their deficiency. In this context, the conjugation of
      these proteins to polymers such as modified dextrans could be used to approach
      the problem. Conjugate formation in concentrated medium ([protein] >50 g/L) is
      well documented, whereas drastic dilution ([protein] <1 g/L) is quite
      unfavorable. Before studying the binding of factor IX and protein C to polymers,
      the coupling of model proteins (human hemoglobin, Hb; human serum albumin, HSA)
      in low-concentration medium to benzenetetracarboxylate dextran (BTC-dextran) and
      dialdehyde dextran was investigated. To obtain soluble benzenetetracarboxylate
      dextran-based conjugates, the conditions of coupling were optimized; the use of
      sulfo-NHS was necessary to form a conjugate with benzenetetracarboxylate dextran.
      In fact, the O-acylurea intermediate formed between coupling agent [1-ethyl-3(3
      dimethylaminopropyl) carbodiimide, EDC] and BTC-dextran must be stabilized.
      Concerning dialdehyde dextran, a more oxidized polymer and a higher pH of the
      buffer of coupling than for highly concentrated solution must be used to obtain a
      conjugate. Whatever polymer is used, HSA appeared clearly less reactive than Hb,
      which can be attributed to the better reactivity of N-terminal amino groups in
      this latter protein and to the marked affinity of benzenetetracarboxylate dextran
      for it. No soluble conjugate was formed between the same dextran derivatives and
      factor IX or protein C. Moreover, the activity of both coagulation factors was
      dramatically decreased by contact with EDC and glutaraldehyde, a small molecule.
      Thus, bad accessibility of protein amino groups is probably responsible for this
      lack of reactivity. Nevertheless, it could be shown that carboxylate and amino
      groups were essential to the activity of factor IX and protein C.

PMID- 9588953
TI  - Isolation: analysis and properties of three bradykinin-potentiating peptides (BPP
      II, BPP-III, and BPP-V) from Bothrops neuwiedi venom.
AB  - In the course of systematic investigations on low-molecular-weight compounds from
      the venom of Crotalidae and Viperidae, we have isolated and characterized at
      least three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from
      Bothrops neuwiedi venom by gel filtration on Sephadex G-25 M, Sephadex G-10
      followed by HPLC. The peptides showed bradykinin-potentiating action on isolated
      guinea-pig ileum, for which the BPP-V was more active than of BPP-II, and BPP
      III, rat arterial blood pressure, and a relevant angiotensin-converting enzyme
      (ACE) competitive inhibiting activity. The kinetic studies showed a Ki of the
      order of 9.7 x 10(-3) microM to BPP-II, 7 x 10(-3) microM to BPP-III, and 3.3 x
      10(-3) microM to BPP-V. The amino acid sequence of the BPP-III has been
      determined to be pGlu-Gly-Gly-Trp-Pro-Arg-Pro-Gly-Pro-Glu-Ile-Pro-Pro, and the
      amino acid compositions of the BPP-II and BPP-V by amino acid analysis were 2Glu
      2Gly-1Arg-4Pro-1Ile and 2Glu-2Gly-1Ser-3Pro-2Val-1Ile, with molecular weight of
      1372, 1046, and 1078, respectively.

PMID- 9588954
TI  - Cleavage specificities of individual members of kallikrein family of proteins on
      synthetic peptide containing the bradykinin sequence.
AB  - We have analyzed the effect on bond specificity of various isolated members of
      the mouse kallikrein family of proteins on a synthetic peptide containing the
      bradykinin sequence. The cleavage pattern shows the selected specificity of these
      proteases toward the synthetic peptide. The Phe-His bond (positions 11-12) in the
      synthetic peptide was favorably cleaved by most of the members in this family,
      including gamma nerve growth factor. On the other hand, the Lys-Arg bond
      (position 3-4) was found to be susceptible only to gamma-NGF. The combination of
      these cleavages could result in the degradation of bradykinin in vivo.

PMID- 9588955
TI  - Xylosylation of alternatively spliced isoforms of Alzheimer APP by
      xylosyltransferase.
AB  - Acceptor affinities of UDP-D-xylose:proteoglycan core protein beta-D
      xylosyltransferase (XT) recognition signals in synthetic L-APP and L-APLP2
      homologous peptides were determined. The Michaelis-Menten constants (KM) of the L
      APP peptide TENEGSGLTNIK and the L-APLP2 peptide SENEGSGMAEQK were 20.1 and 18.9
      microM, respectively. Therefore, the peptides proved to be as good acceptors for
      XT as the bikunin aminoterminus homologous peptide (KM = 22 microM). Due to the
      occurrence of L-APP and L-APLP2 transcripts in human brain tissue, XT activity
      was measured in human liquor cerebrospinalis. Mean values were calculated as 0.22
      mU/L in males and 0.47 mU/L in females without disturbance of blood brain
      barrier. In addition, in homogenized rat brain tissue a mean XT activity of 0.75
      mU/L was determined. Furthermore, XT activity was investigated in 21 different
      human cell lines. In 7 cell lines an enzyme activity was not detected in either
      extracellular space or cytoplasma. Our findings indicate that XT is not
      ubiquitously expressed in human cell types.

PMID- 9588956
TI  - Trends in medical education.
AB  - Undergraduate medical education in the United Kingdom is undergoing major
      changes. These changes are the result of pressures from three different but
      interrelated areas. Alterations in the funding and management of higher education
      and health care, new approaches to curriculum design and advances in clinical
      practice each have significant impact on how medical education is delivered.
      Students, teachers, medical schools and hospital and community practice are all
      affected by these changes.

PMID- 9588957
TI  - Competency-based dental education in context.
AB  - The theoretical foundations of competency-based education are described. Among
      these are definitions of learning in terms of the situations one can function in
      rather than the accumulation of knowledge or skills, and of professional growth
      as a succession of stages from novice to expert. Competence is the midpoint on
      this continuum where individuals are capable of practicing independently and of
      assuming responsibility for their continued professional growth. Dental education
      has functioned well at the early stages of this process, but the assumption that
      "more of the same" will complete the process is questioned. Also considered are
      the implications of competency in the political context of dentistry, in
      curriculum design, and for evaluation.

PMID- 9588958
TI  - Orthodontic competency in predoctoral education in American dental schools.
AB  - Predoctoral orthodontic education is evolving in the United States to reflect the
      move towards competency-based education. This trend focuses on teaching to
      competency in an area or procedure. In orthodontics, this creates a dilemma for
      the educator in determining what orthodontic competency actually is and how to
      achieve it. A survey of United States orthodontic departments was conducted to
      aid in examining the change toward competency-based education in predoctoral
      clinical orthodontics. The results demonstrated a large amount of diversity
      regarding both the definition and the use of competencies. The most recent US
      accreditation standards and guidelines are moving away from specific treatment
      techniques and more towards management and recognition of malocclusions for the
      recently-graduated general dentist.

PMID- 9588959
TI  - Dental education resources on the Web.
AB  - New methods of delivering educational material are being developed in order to
      improve effectiveness and efficiency of learning. They are not designed to
      replace conventional teaching methods, but to complement them and encourage self
      directed learning among students. In the present technological age, the use of
      computers in teaching and learning is almost mandatory. This article describes
      the development of educational aids available on the World Wide Web through the
      project DERWeb (Dental Education Resources on the World Wide Web) and its
      expansion as a site for dental information for the whole dental community.
      Courses and demonstrations to various groups by the team have led to interest and
      uptake by those who were previously unaware of this form of information
      dissemination or were "afraid" to use computers. The project is expanding
      continually and projections for future development are discussed.

PMID- 9588960
TI  - Clinical simulation in teaching preclinical dentistry.
AB  - Current and projected approaches to dental education have created a wide interest
      in clinical simulation, and recently there has been a considerable expansion in
      the availability of experiential learning tools which imitate "real life"
      clinical conditions in dentistry. These include patient simulation devices such
      as heads, jaws, teeth and clinical environments, standardized patients,
      interactive video-discs and computer-based instruction. This paper reviews some
      of the equipment currently available for simulation of clinical procedures, and
      assesses the initial experiences and responses of 2nd, 3rd and 4th year
      undergraduate dental students at The University of Melbourne to case-based
      simulations in a patient simulator in comparison with preclinical exercises in a
      traditional bench and manikin laboratory. Student response to teaching and
      learning in the simulator over a 3-year evaluation period, collected via a
      student questionnaire was uniformly positive. Students were very enthusiastic
      about the learning environment and educational approach, preferring it to
      traditional preclinical laboratory instruction.

PMID- 9588961
TI  - Learning a clinical method to identify a mandibular reference position.
AB  - The teaching of clinical maxillomandibular relationships is an area of weakness
      in dental school curricula. Most difficulties arise when a reference position is
      required to adjust or reconstitute the maximum intercuspation of the dentition.
      The dentist-derived concept of the centric maxillomandibular relation position is
      used to solve this problem. There is no consensus on the definition of this term.
      In the descriptions of clinical technique for recording the centric
      maxillomandibular relation position, clinical criteria to judge whether or not
      the position required has been achieved usually are not given. The dorsal border
      paths of the envelope of movement were used to develop a clinical criterion to
      identify the centric maxillomandibular relation position. Force or "guidance" is
      not used in this method. Test-patients with normal masticatory systems were
      randomly selected and fitted with a mechanical tracking apparatus. 50
      undergraduate dental students and dental nurses were randomly selected and given
      instruction in the clinical technique to identify the centric maxillomandibular
      relation position. The ability of these students to identify the reference
      position was assessed by having them perform the technique blindfolded on the
      test-patients on whom tracking apparatus was fitted. Sixty eight percent of the
      test-clinicians succeeded in using the method to identify the reference position.
      There was no significant difference in the abilities of subgroups to use the
      method successfully, e.g., women compared to men, 2nd year students to 3rd year
      students. It was concluded that the method was a satisfactory way of learning how
      to identify the centric maxillomandibular relation position in a gentle, non
      invasive fashion.

PMID- 9588962
TI  - An investigation into the use of the FDI tooth notation system by dental schools
      in the UK.
AB  - This study investigated the use of the FDI tooth notation system in UK dental
      schools. In addition, the notation system used by dentists referring patients to
      Manchester Dental Hospital was recorded. A questionnaire was sent to the Deans of
      all Dental Schools in the UK and letters of referral to Manchester Dental
      Hospitals Paediatric GA Service were monitored for 1 month. The results showed
      that only Manchester University Dental School used the FDI system but 6 other
      schools instructed students in its use. The Palmer system was used by all the
      other schools for recording clinical information. 136 referral letters were
      received, only one used the FDI notation, 15 used both FDI and Palmer and the
      remainder (120) requested extractions using the Palmer notation. The FDI notation
      system is not used in the majority of UK dental schools. Despite the fact the
      Dental School in Manchester has been teaching and using the FDI system for over
      10 years, it has not been adopted by General Dental Practitioners referring
      patients into the hospital. The FDI should review the use of their system in
      other countries, to ascertain whether it has fulfilled its role as an
      international notation system.

PMID- 9588963
TI  - Gender and research productivity in US and Canadian schools of dentistry. A
      preliminary investigation.
AB  - The purpose of this study was to evaluate individual faculty research
      productivity with respect to gender among clinical faculty in 66 United States
      and Canadian schools of dentistry. A comprehensive survey instrument was
      developed to collect information on factors associated with research productivity
      of individual faculty. The present investigation focused on time spent per week
      in various work related activities (teaching, administration, research, and
      private practice), external grant money obtained for research, and responses to
      12 variables evaluating the subject's perceptions of their research background,
      work environment, attitude and outcome effects from publishing, and the use of
      colleagues in conducting research. The 833 respondents represented a response
      rate of 69.4% (833/1200) from a 50% stratified random sample of faculty who (1)
      had full-time appointments and held at least the DMD or DDS degree or the foreign
      equivalent, (2) taught in a clinical department of the dental school, and (3)
      were not departmental chairpersons or administrators. The majority of subjects
      responding to the survey were male (705 males, 84.6%; 128 females, 15.4%).
      Respondents reported a mean of 10.3 years (males = 10.8, females = 7.5) in full
      time dental education and a mean of 10.1 career publications (males = 11.6,
      females = 6.5; P < 0.001). Although there was no significant difference in weekly
      hours devoted to academic responsibilities between males and females, several
      factors did demonstrate significant gender differences (external grant money
      obtained for research purposes, P < 0.03; feeling that the departmental chair did
      not emphasize research, P < 0.05; feeling a lack of autonomy within their
      institution, P < 0.007; and feeling a lack of available colleagues for research
      purposes, P < 0.001). The implications of the findings are discussed concerning
      strategies for improving research productivity for females in academic dentistry.

PMID- 9588964
TI  - WHO consensus statement on dental amalgam. FDI World Dental Federation.

PMID- 9588965
TI  - Oral cancer. Practical prevention.

PMID- 9588966
TI  - International principles of ethics for the dental profession. FDI World Dental
      Federation.

PMID- 9588967
TI  - Dentist's role in the treatment of snoring & sleep apnea.

PMID- 9588968
TI  - Nutrition. A cellular approach to healthy patients.

PMID- 9588969
TI  - A clinical technique for the management of a Class II skeletal relationship with
      an anterior open bite as a result of long face syndrome in the adult patient.

PMID- 9588970
TI  - Interactive CT diagnostics, planning and preparation for dental implants.
AB  - The insertion of dental implants is multifaceted. Adequate containment of the
      implant body requires not only a measurable volume of bone but also an acceptable
      density of this osseous foundation. Through interactive computerized axial
      tomography (CAT), not only are such measurements conveyed to the clinician, but
      vital structures that should be avoided or at least accounted for are portrayed
      in a three-dimensional manner. Predict-ability is enhanced, and the implants can
      be directed for prosthetic use in conjunction with surgical guides (templates).

PMID- 9588971
TI  - Palatal extension of removable prostheses related to implant positions.
AB  - Once the decision has been made to construct a maxillary implant-supported
      overdenture prosthesis, implant location and number are important determining
      factors for palatal design. Eight clinical scenarios are described. Four cases
      require full palatal coverage, and four cases permit modified palatal coverage.
      Only two, with an increased number of implants and more posterior locations,
      permit a completely open palatal design similar to fixed prostheses.

PMID- 9588972
TI  - A bone quality-based implant system: a preliminary report of stage I & stage II.
AB  - A system is introduced in which dental implants are specifically designed for
      containment within four different categories of bone densities. The sizes and the
      textured surfaces that accompany the gradations of lengths and diameters are
      standardized for each bone type. A modified thread design focuses on compression
      of bone rather than on shear, and the geometry of the entire implant body
      reflects features that are concurrent with a "platform effect." Having been
      tested by means of finite element analysis and initial animal studies, the
      results are provided herein for the placement of 364 consecutive implants in five
      clinical centers on human patients, with surgical survival results of 98.9
      percent overall. The initial clinical report of these implants indicates that all
      bone densities may have similar initial survival rates.

PMID- 9588973
TI  - Use of guide planes and implant supported bar overdentures: a case report.
AB  - A stable occlusal plane is achieved with the combination of two maxillary,
      implant-supported milled bars securing an overdenture and bilateral, mandibular
      fixed partial dentures. Overdenture retention is enhanced with attachments. Guide
      planes assure proper alignment of the overdenture for easy patient insertion and
      improved prosthesis stability. A reliable technique for verifying the accuracy of
      the master cast is also presented.

PMID- 9588974
TI  - An overview of implant marketing.
AB  - Implant dentistry is no longer a new field, but there is still plenty of room for
      it to grow. Over the years, implant dentistry has grown steadily but not as
      quickly as it could. Because of the high degree of complexity and high costs
      associated with practicing implant dentistry, the growth of composite bonding,
      for example, quickly surpassed that of implants. Although each is an answer to a
      desperate dental service need, composite bonding provided the only answer,
      whereas implants have much less costly and less complex alternatives, i.e.,
      dentures. However, with the emergence of high technology in dentistry and young
      dentists who are motivated to use high technology and practice higher revenue
      oriented dentistry, the author believes that implant dentistry will soon begin to
      grow much more quickly than it has over the last 10 years. As technology
      continually facilitates and improves the results of implant dentistry, patients
      will begin to realize the limitation of dentures and will become more comfortable
      with finding a permanent, more attractive, and more valuable alternative.

PMID- 9588975
TI  - An in vitro study of coronal microleakage in root-canal-treated teeth restored by
      the post and core technique.
AB  - The aims of this study were to compare coronal microleakage around cast and
      prefabricated post and cores and to examine the coronal seal achieved by
      temporary post crowns. Thirty extracted, single-rooted, human teeth were prepared
      chemomechanically, root filled with gutta-percha and sealer and prepared for a
      standard post. Three groups, each of 10 teeth, were restored with either: (i)
      cast post and cores cemented with zinc phosphate cement; (ii) prefabricated posts
      and composite cores cemented with a composite luting cement; or (iii) temporary
      post crowns cemented with a temporary zinc oxide-eugenol cement. The teeth were
      thermocycled and placed in Indian ink for 1 week, then demineralized and rendered
      transparent. Linear coronal dye penetration around the posts was measured and
      recorded. Results indicated that while cast post and cores and prefabricated
      posts and composite cores produced a good seal, leakage was significantly greater
      with temporary post crowns (P < 0.05). It is concluded that to prevent re
      infection of the root canal system, it may be preferable to restore the tooth
      immediately with a prefabricated post and composite system rather than place a
      temporary post crown and subsequently a cast post and core.

PMID- 9588976
TI  - Comparison of two endodontic handpieces during the preparation of simulated root
      canals.
AB  - The objective of this in vitro study was to compare and assess two endodontic
      handpieces during the preparation of simulated root canals. One hundred and sixty
      simulated root canals in clear resin blocks, of two angles and positions of
      curvature, were prepared using either Shaper files activated by the MM1500 Sonic
      Air handpiece (Micro-Mega, Besancon, France) or Excalibur files activated by the
      W & H Excalibur 969 handpiece (W & H, Burmoos, Austria). Files of 21-mm or 25-mm
      length were used. When preparing the canals, the files were used either in line
      with or perpendicular to the canal curvature. Preparation of the canals was
      carried out using a technique described in the manufacturers' literature. A
      variety of parameters were used to compare the handpieces, including an
      assessment of the canal preparation time, the deformation or fracture of
      instruments, loss of canal length, weight loss from the resin blocks and the
      overall postpreparation canal shape. Both handpieces provided an efficient and
      easy method of preparing and shaping the root canal with little operator fatigue.
      The MM1500 Sonic Air handpiece took significantly more time (P < 0.001) to
      prepare the canals and was associated with both more loss of working length (P <
      0.05) and more loss of weight (P < 0.001). Both handpieces created a high
      percentage of aberrations in the shapes of prepared canals. The MM1500 Sonic Air
      handpiece created significantly more aberrations than the Excalibur handpiece (P
      < 0.05 for zip and elbow, P < 0.05 for danger zone and coronal narrow). The
      effects of the variables, canal curvature, file length and the plane of use of
      the file, on the performance of the handpieces, were also assessed.

PMID- 9588977
TI  - Bacterial penetration through temporary restorative materials in root-canal
      treated teeth in vitro.
AB  - Seventy extracted single-rooted mandibular premolars were used in this study to
      determine the length of time needed for bacteria present in natural human saliva
      to penetrate through three commonly used temporary restorative materials and
      through the entire root canal system obturated with the lateral condensation
      technique. Five intact teeth with no decay were used in the negative control
      group and five teeth with extensive decay in communication with the canal, in the
      positive control group. The 60 teeth used in the experimental group were divided
      into three groups. In Group 1, the access cavities of 20 teeth were temporarily
      restored with gutta percha, in Group 2 with IRM and in Group 3 with Cavit-G. All
      70 teeth were mounted individually where the crown was placed in contact with
      human saliva. All five teeth in the positive control group caused broth turbidity
      within 24 h. In contrast, broth in the negative control group remained clear
      throughout the entire experimental period. In the experimental group, the average
      time for broth contamination of access cavities closed with gutta percha, IRM and
      Cavit-G was 7.85, 12.95 and 9.80 days, respectively. The Kruskal-Wallis
      nonparametric test showed significant differences among the groups, while the
      multiple comparison test showed that the IRM group was statistically better than
      the gutta percha group when the average lengths of time for contamination were
      compared (P < 0.05).

PMID- 9588978
TI  - Analysis of forces developed during root canal preparation with the balanced
      force technique.
AB  - The aim of this study was to examine the forces and torque developed during root
      canal preparation with the balanced force technique using a recently described
      force-analyser device. A tooth was placed in a holder within the Endograph and
      forces and torques exerted were recorded. These parameters, which can be studied
      during preparation (on-line) or stored and examinated subsequently (off-line)
      generated endograms, which showed the forces generated with time. In addition,
      the endograms of preparations performed by students and endodontists, as well as
      deliberately induced failures in preparation technique (broken instruments), were
      compared. The values for the forces and torques depended on the size of the
      instruments and were related to the phase of the preparation. For the
      endodontists, the vertical and horizontal forces varied, respectively, from 0.08
      +/- 0.01 kg for a size 15 to 0.65 +/- 0.10 kg for a size 45, and from 0.01 +/-
      0.005 kg for a size 15 to 0.4 +/- 0.1 kg for a size 40. The torque varied from
      0.08 +/- 1 kg mm-1 for a size 15 to 1.6 +/- 0.4 kg mm-1 for a size 45. With the
      endograms used as a reference, the relation between the developed vertical forces
      and the torque became more similar between the groups of endodontists and
      students. The Endograph provides a new approach to the analysis of preparation
      technique because it depicts the relationships between the different parameters
      of the preparation.

PMID- 9588979
TI  - Antibacterial activity of calcium hydroxide-containing endodontic sealers on
      Enterococcus faecalis in vitro.
AB  - Antimicrobial activity of endodontic sealers is an important factor in the
      prognosis of root canal treatment. The aim of this study was to analyse the
      antimicrobial activity of calcium hydroxide-containing endodontic sealers,
      Sealapex (SA) and CRCS compared to a ZOE-containing sealer, Roth's cement. The
      sealers were mixed and placed on the side wall of microtitre plate wells. A 10
      microL suspension of Enterococcus faecalis was added to the surface of the
      sealers 1 h, 24 h, or 7 days after mixture. Bacteria were allowed to come into
      contact with the sealers for 1 h at 37 degrees C. Fresh media was then added and
      bacterial growth was measured every 30 min for 16 h. The results showed that in 1
      hour-old mixture, CRCS and Roth's cement had a significantly better antimicrobial
      effect than SA. In 24-hour-old mixtures, ZOE-based sealer showed a more potent
      antimicrobial activity than calcium hydroxide-containing sealers, whereas SA
      showed a significantly better antimicrobial effect in the 7-day-old mixture. The
      antimicrobial activity of each tested sealer changes differently with the time
      interval between mixing and testing, suggesting different physicochemical
      properties and potentially diverse clinical applications.

PMID- 9588980
TI  - Reliability of different electronic apex locators to detect root perforations in
      vitro.
AB  - The aim of this study was to evaluate the accuracy of the electronic apex locator
      Root ZX compared to the Sono Explorer Mark II Junior and Apit III in detecting
      root perforations. Extracted human teeth (n = 30) were perforated artificially in
      the middle third of the root and embedded in a box containing alginate. Detection
      of all perforations were carried out with K-files attached to the apex locators
      tested. The teeth were radiographed after each electronic measurement. The actual
      location of the tip of the file in relation to the external root surface and the
      radiographic determination of the perforations were carried out using a
      stereomicroscope. The mean distance of the tip of the file from the external
      outline of the root surface was short for all instruments and clinically
      acceptable (0.06-0.25 mm). There was no clinically significant difference between
      the morphometric measurements and the radiographic measurements. No statistical
      significance was found between large perforations (0.55-0.60 mm) and small
      perforations (0.25-0.40 mm). Under the conditions of this study, all electronic
      apex locators tested were acceptable clinical tools in the detection of root
      perforations.

PMID- 9588981
TI  - The behaviour of post-retained core materials supported by coronal tooth
      structure in vitro.
AB  - This study was designed to investigate the effect of retaining coronal tooth
      substance on the performance of post-retained core materials, and to compare the
      fracture resistance of the system with an intact tooth prepared to similar
      dimensions. Ten teeth restored with post-retained silver amalgam, and 10 teeth
      restored with silver-glass cermet, all with a retained single wall of coronal
      tooth substance, were compared with 10 unrestored teeth prepared to similar
      dimensions when subjected to a shearing load. The results showed no statistically
      significant difference between the unrestored teeth and those restored with a
      silver-glass cermet. Whilst the teeth restored with silver amalgam had a
      significantly higher fracture resistance (P > 0.01) there was greater tendency to
      root fracture.

PMID- 9588982
TI  - An in vitro investigation of coronal leakage with three gutta-percha backfilling
      techniques.
AB  - The aim of this study was to compare the backfilling capabilities of System B,
      Obtura II and Alphaseal. Forty-six lower premolar teeth were prepared
      chemomechanically and allocated to four experimental and two control groups. Ten
      were obturated using lateral condensation as a standard and 30 were obturated in
      the apical third using the System B. The latter 30 teeth were then backfilled
      using one of three techniques, System B, Obtura II or Alphaseal (n = 10 in each
      group). The remaining six teeth served as controls. Roots were radiographed from
      the proximal in order to evaluate voids and then placed in India ink for 65 h
      prior to being demineralized and rendered transparent, coronal leakage was
      quantified by linear measurement of ink penetration. No significant difference
      was found between the four groups with respect to the presence of voids
      radiographically (P < 0.05). The difference in leakage between the System B and
      Obtura II groups was not significant (P > 0.05). Both System B and Obtura II
      leaked significantly less than Alphaseal and lateral condensation (P < 0.001).

PMID- 9588983
TI  - Incomplete calcium hydroxide removal from the root canal: a case report.
AB  - This case demonstrates failure of root canal treatment of a maxillary central
      incisor following incomplete mechanical removal of a Ca(OH)2 intracanal dressing
      and subsequent resorption of the material from the apical portion of the root
      canal. Retreatment some 4 years later involved the removal of the contents of the
      root canal and permanent obturation by lateral condensation of cold gutta-percha
      with a sealer. Follow-up showed complete periradicular bone healing with a lamina
      dura evident. An explanation of the processes involved is offered, based upon
      histopathological and microbiological evidence in the literature.

PMID- 9588984
TI  - Root canal treatment of a mandibular first molar with three mesial root canals.
AB  - The dynamic concept of the root canal system, describing a variable morphology of
      multiple root canals inter-connected by anastomoses, has been established as the
      prevailing state in mandibular molars. This case report presents the treatment of
      a mandibular first molar with five root canals, of which three were located in
      the mesial root. A third middle root canal was found between the mesiobuccal and
      mesiolingual root canals. The morphological pattern of separate apical
      terminations of the three mesial root canals, as manifested in this case, is a
      very rare one and seldom encountered.

PMID- 9588985
TI  - Treatment of the atrophic edentulous maxilla with implant-supported overdentures:
      a review of the literature.
AB  - PURPOSE: This article reviews the literature on maxillary implant-supported
      overdentures. MATERIALS AND METHODS: Retrospective studies and clinical reports
      comprise the majority of publications, with few prospective studies. RESULTS:
      Maxillary implant-supported overdentures are associated with implant and
      prosthesis survival rates similar to those of fixed implant prostheses when
      patients are matched for bone quantity and quality. High failure rates are
      associated with extreme atrophy, poor bone quality, and the use of short
      implants, which represent situations in which overdentures are most commonly
      used. CONCLUSION: Further research is required to elucidate the most appropriate
      implant number and distribution as well as the most favorable prosthetic
      constructions.

PMID- 9588986
TI  - Tensile bond strength of porcelain teeth to denture resin before and after aging.
AB  - PURPOSE: This in vitro study compared the effects of four surface treatments on
      the bond strength between porcelain denture teeth and heat-polymerized denture
      base acrylic with and without a ceramic primer and bonding agent and after three
      storage conditions. MATERIALS AND METHODS: Polished porcelain specimens (120)
      were divided into 24 groups of five each as follows: surface treatments (none,
      etched, sandblasted, and air abraded), ceramic primer and bonding agent (yes and
      no), and storage conditions (water storage, thermocycling, and accelerated
      aging). All the specimens were tested to failure in tension on a testing machine.
      RESULTS: Hydrofluoric acid etching, sandblasting, and air abrasion did not
      improve the bond strength of specimens without ceramic primer and bonding agent
      compared to those polished with 600-grit silicon carbide paper. Use of ceramic
      primer and light-activated bonding agent (Scotchbond MP) increased the bond
      strength. For thermocycled specimens treated with ceramic primer and bonding
      agent, the bond strengths ranged from 10 to 31 MPa in the following order: air
      abraded = etched < no treatment < sandblasted. CONCLUSIONS: Ceramic primer and
      bonding agent dramatically improved the bond strength of porcelain teeth to heat
      polymerized denture resin. Sandblasting improved bond strength of bonded samples
      compared to those that were etched or polished only.

PMID- 9588987
TI  - Microhardness and surface topography of a composite resin cement after water
      storage.
AB  - PURPOSE: The aims of this study were to assess changes in the microhardness and
      surface roughness of a dual-cured composite resin cement after water storage for
      different periods of time. MATERIALS AND METHODS: Sixty specimens were divided
      into four groups comprising high- and low-viscosity cement specimens stored
      either dry or in water for 1 to 60 days. Microhardness and surface roughness
      measurements were made after 1, 7, and 60 days of storage. RESULTS: It was found
      that that although interactions complicated the interpretation of the results,
      the water-stored samples had a significantly lower microhardness compared to the
      dry-stored specimens for every time interval. In addition, the high-viscosity
      specimens had a significantly higher microhardness compared to the low-viscosity
      specimens. An increased microhardness was found for all groups, except for the
      low-viscosity, water-stored specimens after 60 days of water storage, which was
      attributed to an effect of the chemical postcuring process. Although difficult to
      evaluate from a clinical point of view, the laser profilometry analysis revealed
      that a significantly increased surface roughness was found after water storage
      and increased storage time that was possibly caused by a deterioration of the
      resin-matrix surface. CONCLUSION: For the permanency of the interfacial luting
      material, a high microhardness value seems to be important.

PMID- 9588988
TI  - Influence of glass-ceramic thickness on Hertzian and bulk fracture mechanisms.
AB  - PURPOSE: The objective of this study was to test the hypothesis that bulk
      fracture of glass-ceramic disks of variable thickness originates at the inner,
      resin-bonded surface and is dominant over Hertzian fracture at the lower range of
      thickness values. MATERIALS AND METHODS: Eight groups of seven glass-ceramic
      disks (Dicor, Dentsply), 12 mm in diameter with thicknesses ranging from 0.4 to
      2.4 mm, were cast, cerammed (to produce approximately 55 vol% of tetrasilicic
      fluormica crystals), air abraded, etched, and silane coated according to the
      manufacturer's instructions. The disks were bonded to an epoxy die substrate
      (with an elastic modulus comparable to that of dentin) using a light-activated
      resin cement. The bonded samples were supported on a flat surface and loaded at
      the top center of each disk until crack initiation occurred. All disks exhibited
      an initial crack within the bonded surface. Three randomly selected samples for
      each thickness were loaded beyond the point of crack initiation until Hertzian
      failure occurred. RESULTS: Although the crack-initiation force increased with
      increasing thickness, the failure stress approached a maximum level at a
      thickness of approximately 1.6 mm. These results suggest that the estimated
      maximum occlusal load for each patient should be used to select the minimum
      thickness of ceramic crowns rather than using the arbitrary traditional selection
      of a 1.5-mm thickness. CONCLUSIONS: The authors conclude that bulk fracture is
      initiated within the bonded surface of a glass-ceramic specimen (for samples 0.4
      to 2.4 mm in thickness) when the glass-ceramic is supported by a substrate with
      an elastic modulus similar to that of dentin. Furthermore, a Hertzian failure
      mechanism is unlikely to cause bulk fracture for these conditions.

PMID- 9588989
TI  - Interfacial reactions of cast titanium with mold materials.
AB  - PURPOSE: Dental casting requires replication of complex shapes with high
      fidelity. To achieve this objective, the problem of scale formation on titanium
      dental castings must be overcome. Scaling occurs readily at high temperatures
      because of the high reactivity of molten titanium with investment materials. The
      purpose of this study was to examine the effectiveness of using stable oxide
      coatings on the mold surface to reduce the interfacial reactions. MATERIALS AND
      METHODS: A traditional phosphate-bonded dental investment, a commercial titanium
      investment, and an experimental oxide coating were used for the molds. Pure
      titanium samples were cast, divested, and prepared for scanning electron
      microscopic and energy dispersive x-ray spectroscopic analyses. RESULTS: Layers
      of 7- to 10-micron-thick scale were formed on titanium castings during reaction
      with traditional mold materials. Interface reaction was reduced between the
      molten titanium and the investment material when yttrium oxide or zirconium oxide
      coatings were applied to the mold before casting. CONCLUSION: Less titanium-mold
      interfacial reactions occurred when protective coatings were used as diffusion
      barriers for titanium casting. Y2O3-coating oxide particles applied without
      binder were entrapped in the cast titanium surface layer. Further study of a
      binder system for Y2O3 coating is needed.

PMID- 9588990
TI  - Preliminary evaluation of tin plating for extracoronal restorations: evaluation
      of marginal quality and retention.
AB  - PURPOSE: The influence of tin plating on marginal seating and retention of
      complete cast crowns was evaluated. MATERIALS AND METHODS: Thirty-six
      standardized gold-alloy complete crowns were made on extracted human molar teeth
      prepared with a modified milling machine using conventional laboratory
      techniques. The crowns were randomly assigned to two groups according to the
      treatment of the fitting surface (air abraded with 50-micron aluminum oxide for
      10 seconds, or tin plated with a microtin system for 3 seconds), and luted with
      adhesive resin cement (Panavia-EX, J. Morita). Scanning electron microscopy was
      used to evaluate the variables for the cast alloy. Retention was measured with an
      instron testing machine after thermocycling (1,500 cycles between 5 degrees C and
      55 degrees C with 1 minute dwell times). Marginal adaptation was measured with a
      Nikon microscope before and after cementation. Results were subjected to one-way
      analysis of variance and Student's t test. RESULTS: Retention was significantly
      different (P < 0.001); the highest retention (367 N) was reported in tin-plated
      crowns. Differences for marginal seating were not statistically significant.
      CONCLUSION: Tin plating after air abrasion was found to be a predictable and
      simple technique to roughen the casting surface, increase the surface area for
      bonding, and significantly improve the retention of cast crowns in vivo.

PMID- 9588991
TI  - Effect of water sorption on the resistance to plastic deformation of a denture
      base material relined with four different denture reline materials.
AB  - PURPOSE: The effect of water sorption on the flexural strength at the
      proportional limit (FSp) of a denture base material relined with four different
      denture reline materials was studied. MATERIALS AND METHODS: Denture base
      specimens were relined either after 24 hours or 30 days of water immersion. The
      relined specimens were tested after another period of 24 hours or 30 days of
      water immersion. RESULTS: Relined denture specimens generally exhibited lower FSp
      with an increase in water immersion time and an increase in the thickness of the
      reline material. CONCLUSIONS: The plasticizing effect of absorbed water molecules
      explains the general decrease in FSp of immersed relined specimens. The absence
      of a significant effect that water immersion had on some relined specimens under
      certain immersion conditions was explained by water sorption into the denture
      base achieving an equilibrium after a period of water immersion, and the
      resistance of some reline materials to the effect of water immersion.

PMID- 9588992
TI  - Reduction of implant loading using a modified centric occlusal anatomy.
AB  - PURPOSE: This paper focuses on the derivation of implant loading forces as
      influenced by occlusal anatomy. Vertical occlusal forces on cusp inclines produce
      resultant lines of force that result in lateral rather than vertical forces to
      the supporting bone. MATERIALS AND METHODS: An analysis of resultant lines of
      force with different impacting occlusal surfaces was illustrated. Methods were
      suggested to decrease implant loading by reducing cusp inclines, utilization of
      cross occlusion, and the modification of occlusal anatomy to provide a continuous
      1.5-mm flat fossae, rather than the line angles of the usual cuspal anatomy. The
      relationship of incisal guidance to the cusp inclines on the adjustable
      articulator were reviewed. Modification of the incisal pin and articulator
      settings were suggested to produced a 1.5-mm fossae throughout the prosthesis.
      Practical laboratory and intraoral occlusal adjustment techniques were suggested
      to provide a modified centric occlusal anatomy to help decrease implant loading.
      RESULTS: Clinical examples were shown to verify the accuracy of the modified
      settings on the semi-adjustable articulator and the resultant modified occlusal
      anatomy. CONCLUSION: Implant loading can be reduced by modifying the location of
      the impact area and the occlusal anatomy. Simple modification of the incisal pin
      and articulator settings can be used to produce a 1.5-mm flat fossae, which
      results in more vertical forces to the supporting bone. The same procedures are
      used to reduce cusp inclinations, which effectively lessens the torque exerted on
      the prosthesis, implant, and bone. A combination of all these factors can prevent
      implant overload.

PMID- 9588993
TI  - Radiopacity of dual-cured and chemical-cured resin-based cements.
AB  - PURPOSE: The objective of this study was to determine radiopacity values of a
      group of resin-based cements and to compare them to those of enamel and dentin.
      MATERIALS AND METHODS: Three specimens 2.5 mm thick were prepared from each of 18
      cements (nine chemical-cured and nine dual-cured). Three tooth sections 2.5 mm
      thick were cut from extracted molars. Specimens and tooth sections were divided
      into three matching groups. Following standard radiographic techniques, images of
      each group of specimens, along with an aluminum step wedge were obtained. Optical
      density readings for each material were determined with a transmission
      densitometer. Radiopacity values were subsequently calculated as equivalents of
      aluminum thickness. RESULTS: Analysis of variance indicated significant
      differences in radiopacity values among the materials (P < 0.0001). Four dual
      cured cements (Variolink, Geristore, Enforce, and Nexus) had radiopacity values
      significantly greater than that of enamel, while two (Choice and Adherence) had
      radiopacity values similar to enamel. For the remaining three dual-cured cements,
      Duolink had a radiopacity value significantly lower than that of enamel but
      higher than that of dentin, while both Lute-It and Resinomer had values similar
      to dentin. For the chemical-cured cements, five materials had radiopacity values
      significantly higher than enamel (Sealbond, Advance, Scotchbond, Cement-It, and
      Dyract-Cem), while two had values significantly lower than enamel but higher than
      dentin (Biomer and Panavia 21). The remaining two cements had radiopacity values
      significantly lower than dentin. CONCLUSION: For a group of 18 resin-based
      cements, some had radiopacity values similar to or significantly lower than that
      of dentin.

PMID- 9588994
TI  - Adherence of phenotypically switched Candida albicans to denture base materials.
AB  - PURPOSE: The purpose of this study was to investigate in vitro the levels of
      adhesion of phenotypically switched and nonswitched Candida albicans to the
      smooth and rough surfaces of heat-cured acrylic resin, Molloplast B, and Novus.
      MATERIALS AND METHODS: Nonswitched and switched cells of C. albicans 3153A were
      prepared and adhesion assays were performed. RESULTS: There was no difference in
      the level of adhesion of blastospores in their nonswitched or switched state. The
      adherence of hyphae to all three denture base materials was statistically
      significantly increased when in a switched form. There was greater adhesion to
      the two soft lining materials than to the acrylic resin. CONCLUSIONS: Rough
      surfaces promote adhesion. There was no significant difference in the adhesion of
      switched and nonswitched blastospores, but there was increased adhesion of hyphal
      cells.

PMID- 9588995
TI  - Lactobacillus species associated with active caries lesions.
AB  - Lactobacilli that are most frequently associated with active caries lesions in
      dentine were isolated and identified as part of a research project which aims to
      determine the role of the predominant species of these organisms in the carious
      process. Samples of carious dentine were collected from 12 patients with open
      caries lesions (Group A) and stimulated saliva samples were collected from 12
      patients with a DMFT = 0 and confirmed presence of lactobacilli in the oral
      cavity (Group B). After serial dilutions samples were plated on Rogosa agar and
      incubated anaerobically at 37 degrees C for 48 hours. Representative colonies
      were isolated from each sample, using Harrison's disc and species were identified
      by classical taxonomy. A total of 153 isolates were identified. The redefinition
      and description of lactobacilli species in recent systematic literature resulted
      in a new and different species composition of oral lactobacilli as shown in this
      study, namely: homofermentative species (Group A = 82 per cent; Group B = 90 per
      cent) were predominantly Lactobacillus paracasei (Group A = 39 per cent; Group B
      = 30 percent) and Lactobacillus rhamnosus (Group A = 31 per cent; Group B = 41
      per cent). Heterofermentative species (Group A = 18 per cent; Group B = 10 per
      cent) were predominantly Lactobacillus fermentum (Group A = 68 per cent; Group B
      = 100 percent).

PMID- 9588996
TI  - A rapid epidemiological assessment of dental erosion to assist in settling an
      industrial dispute.
AB  - A rapid epidemiological assessment (REA) of industrial dental erosion was
      undertaken with the aim of formulating a range of treatment strategies which
      could be used to settle an industrial dispute. This dispute concerned
      compensation for a group of adult male metalworkers who had complained of dental
      sensitivity and that their teeth had been "eaten by acid" at their workplace, an
      electroplating factory in Springs near Johannesburg, South Africa. The REA
      methods employed included a clinical examination, a structured socio-demographic
      questionnaire and colour photographs of each subject. Sixty per cent of the
      subjects reported pain and/or sensitivity to eating and/or drinking, 76 per cent
      showed varying degrees of loss of tooth structure, and 25 per cent reported teeth
      had been lost as a result of the industrial erosion. The project involved
      negotiating with mine management and trade union representatives, each with
      conflicting interests, and with people's oral health and large sums of money at
      stake. In this context, the aim of the research was to design an instrument to
      resolve conflict and to promote oral health at an industrial site, while
      retaining scientific objectivity and rigour. As a result of the REA, the workers
      who were examined are in the process of being compensated, while the National
      Union of Mineworkers and mine management are engaged in reaching a settlement.
      Preventive measures have been initiated at the factory. The area has been
      declared a "respiratory zone", which makes the wearing of respiratory masks
      obligatory.

PMID- 9588997
TI  - Failure of apicoectomy surgery and successful endodontic retreatment.
AB  - The optimal way to address endodontic failures is to retreat the root canal
      system first and only then to consider apical surgery. Unfortunately, in
      practice, it is often not done in this way. Patients are subjected to apical
      surgery, without any attempts at retreatment. A series of cases is presented
      illustrating failures of apicoectomy and successful endodontic retreatment.

PMID- 9588998
TI  - Student attitudes to dentistry in South African dental schools.
AB  - The present study investigated student motives for choosing dentistry in five
      South African dental schools. An attitude questionnaire was complied and
      administered to all entering students at these schools. The study population
      comprised 161 students, 92 males and 69 females. Results indicate that in spite
      of the changing student populations at all universities, the motives for studying
      dentistry remain essentially the same. Similarities in attitudes to dentistry
      tend to outweigh differences. Similarities are shown with respect to service, the
      need for status, independence and financial security. Differences are reflected
      in the contradictions between service and status, service and regular working
      hours, service and financial security. The question these findings raise, is how
      and to what extent students selected for training, based on their current
      motivation and attitudes will best adapt to changes in the practice of dentistry,
      health policies, and increased population demands.

PMID- 9588999
TI  - HIV and the dental profession.
AB  - In order to assess the response of dentists to the increasing incidence of HIV, a
      study was conducted to explore their attitudes, knowledge and the additional
      costs involved in treating HIV positive patients. The response of dentists to the
      increasing incidence of HIV positive patients is influenced by their fears and
      concerns about HIV, their knowledge about the disease, and their attitudes
      towards providing care for HIV patients. The results of this research suggest
      that the negative response to HIV patients from dentists can be attributed to
      several factors. Dentists are afraid of contracting the virus, they do not trust
      the honesty of HIV patients, and they believe there are additional costs involved
      in treating these patients. In order to provide quality dental treatment for HIV
      patients, dentists must overcome their misperceptions and feelings of anxiety and
      fear about HIV. Education is a major weapon in the fight against HIV. Dentists
      agree there is a need for continuing education despite the fact that their
      overall knowledge about HIV is good.

PMID- 9589000
TI  - Oral health finance and expenditure in South Africa.
AB  - The objective of this paper was to examine the cost of oral health in South
      Africa over the past decade Particular emphasis was placed on the contribution
      made by medical schemes which is the main source of private health care funding.
      Some of the problems facing this huge industry were also briefly explored.
      Primary aggregate data on oral health expenditure were obtained from the
      Department of Health, Pretoria and from the offices of the Registrar of Medical
      Schemes, Pretoria. The results show that in 1994, 4.7 per cent of the total
      health care budget was allocated to oral health. Of this amount, 14.2 per cent
      came from the state, 71.9 per cent from medical schemes and the remainder
      calculated to be from direct out-of-pocket payments. Furthermore, real
      expenditure for oral health by medical schemes grew robustly and almost
      continuously from 1984 through to 1994, generally outstripping medical inflation.

PMID- 9589001
TI  - Shear bond strength of amalgam and gallium alloys to dentine.
AB  - The purpose of this in vitro investigation was to determine the shear bond
      strength of admixed (Dispersalloy), irregular (Oralloy) and spherical (Lojic)
      amalgams, as well as an admixed gallium alloy (Galloy) to superficial, buccal,
      human dentine surfaces, using the Scotchbond Multi-Purpose Plus system. The bonds
      were stressed to failure in an Instron testing machine after 48 hours, and the
      following values (MPa) were obtained: Admixed = 7.74 +/- 0.7; Irregular = 9.47 +/
      1.4; Spherical = 9.82 +/- 2.4; Galloy = 11.03 +/- 2.5. Data were statistically
      analysed and fracture sites examined in a scanning electron microscope. Galloy
      demonstrated a statistical significant higher shear bond strength than to the
      other types of amalgams (p < 0.01).

PMID- 9589002
TI  - Incisor trauma follows early loss of molars.

PMID- 9589003
TI  - The equitable distribution of the scarce resources of medical aid schemes:
      viewpoint of the dental profession.

PMID- 9589004
TI  - Drug-induced gingival hyperplasia and its management--a literature review.

PMID- 9589005
TI  - Promoting oral health in South Africa: public perceptions of water fluoridation.
AB  - Public knowledge of water fluoridation (WF), sources of information, purpose of
      WF and the level of support for the implementation of WF was assessed in South
      Africa. Of the 2229 respondents interviewed, 23 per cent had heard or read about
      WF. Almost a third said they obtained their information from schools or community
      networks while 60 per cent mentioned either radio, newspapers/magazines, or
      television. About 25 per cent correctly recognized the protection of teeth as the
      purpose of fluoridation, while two-fifths believed the purpose of WF is to purify
      water. More than sixty per cent of respondents were in favour of WF, with almost
      a quarter of the sample feeling uncertain. This study demonstrates that a
      considerable amount of educational and political action is required for water
      fluoridation to be implemented in South Africa.

PMID- 9589006
TI  - A simple method for the determination of sex from the pulp of freshly extracted
      human teeth utilizing the polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) has been used to amplify a region of the ZFX
      and ZFY genes from DNA in human blood and other tissues, for determination of the
      sex of an individual. In the present study DNA was extracted from the pulp of 21
      male and 24 female fresh human third molar teeth. A region of the ZFX and ZFY
      genes was amplified by PCR and analysed by digestion of the amplified DNA with
      HaeIII restriction endonuclease. The digested PCR products were run on a 2 per
      cent agarose gel. Males were distinguished from females by having a fragment of
      317 base pairs which was absent in females. Identification of the sex of the
      individual was 100 per cent accurate in each case. A blind study of random
      samples of the same teeth, used to assess the reproducibility of the technique
      evoked an identical result. This method provides an accurate alternative to
      skeletal measurements and histological staining techniques for the sexing of
      individuals from small amounts of DNA.

PMID- 9589007
TI  - The role of the general dental practitioner in criminal investigations and victim
      identification.

PMID- 9589009
TI  - Micro fracture--efficient diagnosis.

PMID- 9589010
TI  - Controversies in the management of lower urinary tract symptoms: an overview.

PMID- 9589008
TI  - Transverse root fracture and its treatment.

PMID- 9589011
TI  - Clinical pharmacology of modern antihypertensive agents and their interaction
      with alpha-adrenoceptor antagonists.

PMID- 9589012
TI  - Hypertension in the elderly: state-of-the-art treatment.

PMID- 9589013
TI  - Drug treatment of hypertension in the elderly: the role of alpha-adrenoceptor
      blockade.

PMID- 9589014
TI  - Treatment guideline in the USA: hypertension in the elderly.
AB  - According to the JNC-5, at least six classes of antihypertensive agents have been
      synthesized and currently recommended for initial antihypertensive therapy in the
      USA for elderly patients. Each class is safe and effective in reducing arterial
      pressure, each has its own specific mechanism(s) of action that suppress specific
      pressor mechanisms, and each has its own side-effects which may be overcome by
      substituting a drug from another class of agents. In the case of adrenergic
      inhibitors, more specific agents have been introduced over the years. Each
      succeeding new class has obviated certain adverse effects of an earlier class. In
      the case of alpha-adrenergic receptor inhibitors, this concept is of particular
      value with the alpha 1A-receptor inhibiting compounds. The alpha 1-adrenergic
      inhibitors have special value for elderly patients with BPH as both hypertension
      and the prostatic disease can be treated with one compound. The alpha 1A
      antagonists may have particular value in those patients in whom further reduction
      of arterial pressure is not desired and this obviously includes the normotensive
      elderly patient and the hypertensive patient whose blood pressure is already well
      controlled by other agents.

PMID- 9589015
TI  - The pathophysiology of lower urinary tract symptoms in the ageing male
      population.

PMID- 9589016
TI  - Pharmacotherapy for benign prostatic hyperplasia--the potential for alpha 1
      adrenoceptor subtype-specific blockade.

PMID- 9589017
TI  - Current status of research on prostate-selective alpha 1-antagonists.

PMID- 9589018
TI  - Treatment of benign prostatic hyperplasia and hypertension in elderly
      hypertensive patients.

PMID- 9589019
TI  - A critical evaluation of technological innovations in the treatment of
      symptomatic benign prostatic hyperplasia.

PMID- 9589021
TI  - [Stress echocardiography with physical burden using step-climbing for the
      diagnosis of ischemia].
AB  - OBJECTIVE: To ascertain the reliability of stress echocardiography (SEG) with a
      standardized step-climbing test in predicting significant coronary heart disease
      (CHD) in patients suspected of having CHD, subsequently verified by coronary
      angiography. PATIENTS AND METHODS: 174 consecutive patients (116 men, 58 women;
      average age 60 years) suspected of having CHD or with suspected progression of
      known CHD were included. RESULTS: Compared with coronary angiography SEG had a
      sensitivity of 81% for the recognition of ischaemia in patients with coronary
      artery stenosis of 50% or more, with a specificity of 74%. The positive and
      negative predictive values were 81% and 73%, respectively. Multi-vessel disease
      was better recognized then single-vessel involvement. Abnormal perfusion in the
      region supplied by the left anterior descending artery (LAD) was diagnosed with a
      higher sensitivity than those of the circumflex branch (CXB) and the right
      coronary artery (RCA/CXB). For 50% stenoses in the LAD distribution the
      sensitivity was 76%, specificity 79%; for the combined RCA/CXB and CXB areas the
      sensitivity was 52%, specificity 84%. When comparing the SEG findings with
      coronary stenoses of 50%, the sensitivity for diagnosing ischaemia rose to 86%,
      specificity 70%. Positive and negative predictive values were 83% and 75%,
      respectively. Ischaemia in the LAD distribution area was recognized with a
      sensitivity of 79%, specificity 72%, ischaemia in the combined RCA/CXB and CXB
      areas with a sensitivity of 56%, specificity 82%. CONCLUSION: Stress
      echocardiography with stair-climbing can achieve acceptable results in the
      diagnosis of coronary heart disease.

PMID- 9589022
TI  - [Churg-Strauss syndrome with right ventricular tumor].
AB  - HISTORY AND CLINICAL FINDINGS: A 47-year-old woman was admitted because of
      diarrhoea (3-5 stools daily) for 9 days, weakness for 3 weeks and painful wrist
      swelling, arthralgia and hyperesthesia over the medial aspect of the right thigh
      for 6 weeks. For 6 years she had been treated for asthma. Two operation had been
      performed for chronic sinusitis. ADMISSION FINDINGS AND INVESTIGATIONS: There was
      marked eosinophilia (5889/microliter) and thrombocytopenia (96,000/microliter),
      markedly increased serological inflammatory parameters and a raised total IgE
      level (134 IU/ml). The chest radiogram showed pulmonary infiltrates and bone
      marrow biopsy indicated eosinophilia. Echocardiography revealed a mass, 3 x 8 cm,
      in the ventral wall of the right ventricle with extension into the outflow tract.
      DIAGNOSIS, TREATMENT AND COURSE: These findings met the criteria of the American
      College of Rheumatology for Churg-Strauss syndrome (CSS). On methylprednisolone
      (1 mg/kg daily) the eosinophil and platelet counts became normal within 5 days
      and erythrocyte sedimentation rate and the level of C-reactive protein fell.
      Under cardiopulmonary bypass the tumour was removed, the tricuspid valve
      replaced, and the right ventricle reconstructed. Histology of the mass revealed
      it to be an organized thrombus. CONCLUSION: The relationship between the thrombus
      formation and CSS is unclear. Hypercoagulability connected with the inflammatory
      process may have played a part in the pathogenesis.

PMID- 9589023
TI  - [Paraneoplastic cerebellar degeneration in Hodgkin's disease].
AB  - HISTORY AND CLINICAL FINDINGS: A 30-year-old previously healthy man suddenly
      developed double vision, unsteady gait and some difficulty in speech
      articulation. Within 4 weeks he had become markedly ataxic, unable to walk, stand
      or sit down unaided. Neurological examination indicated a severe cerebellar
      syndrome. There were no other abnormal findings on physical examination.
      INVESTIGATIONS: There was no pleocytosis and no oligoclonal bands in
      cerebrospinal fluid (CSF). A test for anti-Purkinje cell antibodies was negative
      in both CSF and serum. Computed tomography and nuclear magnetic imaging (NMI) of
      the brain were normal. TREATMENT AND COURSE: As a para- or postinfectious or
      paraneoplastic process was suspected. I.v. immunoglobulin and oral
      corticosteroids were administered, but without improvement. 13 month later, a
      mediastinal mass was noted on a chest radiogram. This led to the diagnosis of a
      stage IA Hodgkin's disease. Retrospectively the cerebellar degeneration was most
      likely a paraneoplastic change related to the Hodgkin's disease. However, an
      independent second disease cannot be excluded. While the treatment of Hodgkin's
      disease was successful, the neurological symptoms remained unchanged. Severe
      cerebellar atrophy was demonstrated on NMI. CONCLUSION: In case of cerebellar
      atrophy of undetermined aetiology a paraneoplastic cause should be considered and
      an underlying malignant disease looked for.

PMID- 9589024
TI  - [Diagnostic methods for species-specific differentiation of various
      dermatophytes. Possibilities and limitations].

PMID- 9589025
TI  - [Cyclospora cayetanensis--an intestinal protozoan pathogenic for humans which is
      of increasing clinical significance].

PMID- 9589026
TI  - [Settlement claim for the preparation of expert opinions by assistant physicians.
      Decision of the Federal Industrial Court on February 20, 1997].

PMID- 9589027
TI  - [Hormone loss in nephrotic syndrome].

PMID- 9589028
TI  - [Castleman's disease--unusual cause of a febrile state with lymphadenopathy].

PMID- 9589029
TI  - Familial hearing loss and cisplatin therapy.
AB  - Familial high-tone hearing loss in males is a recessive trait often unrecognized.
      Cisplatin chemotherapy may be associated with hearing loss. A review was made of
      audiograms in 85 patients with testicular carcinoma prior to cisplatin
      chemotherapy to determine the extent of preexisting familial hearing loss.
      Clinical histories defined patients exposed to high noise levels and other common
      causes of hearing loss. Audiometric findings were classified according to normal
      hearing or mild, moderate, and severe hearing impairment. Pretreatment audiograms
      were normal in 51 patients and abnormal in 19 patients with histories of high
      level noise exposure, and in 15 patients with high-frequency hearing loss there
      was no history of noise exposure, ear infection, or other potential causes of
      hearing loss. These last 15 patients were judged to have recessive familial
      hearing loss. Awareness of familial hearing loss is important in male patients in
      whom cisplatin chemotherapy is planned. Pretreatment hearing assessment,
      including audiograms, is recommended for such male patients.

PMID- 9589030
TI  - Malignant melanoma in an HIV-infected man: a case report and literature review.
AB  - Although it is not proven by causative association, several studies indicate that
      patients with acquired immune deficiency syndrome (AIDS) have a high risk for
      developing cutaneous malignancies, especially lymphoma and Kaposi's sarcoma.
      Other malignant cutaneous lesions seen in this patient population include basal
      cell carcinoma, squamous-cell cancer, Bowen's disease, and rarely, malignant
      melanoma. We review the clinical course of a human immunodeficiency virus (HIV)
      infected man with a superficial spreading melanoma of the scapula treated with
      wide local excision. Ten years later, he was diagnosed as having metastatic and
      widespread disease. By placing our patient's experience in context with other
      case reports, we sought to determine whether malignant melanoma in the HIV
      infected population presents atypically or has a more aggressive natural history.
      The appearance of malignant melanoma in homosexual men may be coincidental or
      reflective of the expanding spectrum of HIV-associated diseases. Of the 22
      patients reported to have malignant melanoma and HIV, approximately one-third had
      metastatic disease at the time of initial examination, and those with a decreased
      CD4+ cell count were most likely to have systemic symptoms. Melanomas among
      patients with HIV infection were often atypical in appearance, being multiple or
      metastatic, as is the case in other well-defined immunosuppressed groups. Further
      epidemiological and clinical studies are required to determine whether melanoma
      occurs more frequently or is more likely to metastasize in persons with HIV
      disease. Laboratory investigators must also concentrate on those factors in the
      setting of HIV disease that may contribute to melanocyte activation. Our
      patient's fulminant clinical course should alert clinicians to carefully evaluate
      patients with HIV infection and unusual pigmented cutaneous lesions, or who have
      a prior history of malignant melanoma.

PMID- 9589031
TI  - Magnetic resonance imaging detects suppression of tumor vascular permeability
      after administration of antibody to vascular endothelial growth factor.
AB  - Macromolecular contrast medium-enhanced magnetic resonance imaging (MRI) and
      tumor-volume measurements were applied to monitor the effects of anti-vascular
      endothelial growth factor (anti-VEGF) antibody on microvascular characteristics
      and tumor growth of MDA-MB-435 human breast cancer cells implanted in nude rats.
      Administration of anti-VEGF antibody (three 1 mg doses at 3-day intervals)
      induced significant reductions in tumor growth rates (p < 0.05) and in MRI
      assayed microvascular permeabilities (p < 0.05). Results of the study were
      consistent with previous observations that new microvessels formed in response to
      angiogenesis are hyperpermeable, and with the hypothesis that hyperpermeability
      is a mechanistic element in angiogenesis. Variations in tumor-vessel
      hyperpermeability can be measured by contrast-enhanced MRI, which may prove
      useful for assessing antiangiogenesis therapy.

PMID- 9589032
TI  - Alterations in total iron, zinc, and calcium levels and their influence on the
      hepatic activities of gamma-glutamyl transferase and glucose-6-phosphatase in the
      host bearing transplantable murine lymphoma.
AB  - The levels of iron, zinc, and calcium in liver as well as serum, together with
      the enzymatic activities of gamma-glutamyl transferase (GGT, EC 2.3.2.2) and
      glucose-6-phosphatase (G-6-Pase, EC 3.1.3.9) in liver, were critically monitored
      over various periods in male Swiss albino mice bearing Dalton's lymphoma (DL), a
      transplantable ascites-producing tumor. Both hepatic and serum contents of iron,
      zinc, and calcium were found to be maximally elevated (p < 0.001) on day 15 after
      tumor transplantation as compared with their contents in normal animals. There
      was a gradual increase in the activity of GGT in liver in lymphoma-bearing mice
      in comparison with their normal counterparts, which showed a maximum peak (p <
      0.001) on day 15, followed by a continuous and sharp fall. Hepatic G-6-Pase
      activity was found to decrease continuously throughout the progression of
      lymphoma as compared with its levels to normal animals. Tumor-cell counts in
      peritoneal lymph fluids of mice containing DL yielded a maximum count of 155.7 x
      10(3) cells/mm3 on day 15. A significant correlation was observed among the
      levels of different metals, enzymatic activities, and tumor-cell counts at
      different periods of study. From these results, it can be concluded that the
      metals studied may have a role in initiating and controlling cellular
      proliferations, through their effects on modulating the activities of the
      possibly preneoplastic and neoplastic marker enzymes named above.

PMID- 9589033
TI  - Biomodulation of Fluorouracil in colorectal cancer.
AB  - 5-Fluorouracil (5-FU) remains the agent of choice for the treatment of colorectal
      cancer. Research has focused on the biomodulation of 5-FU in order to attempt to
      improve the cytotoxity and therapeutic effectiveness of this drug in the
      treatment of advanced colorectal cancer. Modulation of 5-FU by methotrexate
      (MTX), trimetrexate (TMTX), interferon-alpha (IFN-alpha), leucovorin (LV), or N
      (phosphonacetyl)-L-asparte acid (PALA) has produced higher response rates than
      those observed with 5-FU alone. Methotrexate may improve the durability of
      response to or survival with 5-FU, but with inferior results compared with those
      in trials of 5-FU and leucovorin. Trimetrexate produces a number of responses,
      and further phase III trials are in progress to confirm the results of promising
      phase II trials with this drug. IFN-alpha has shown therapeutic efficiency when
      combined with 5-FU alone or with 5-FU and leucovorin, but latest studies with
      these combinations have shown increased toxicity. Initial single-institution
      phase I trials with 5-FU and PALA reported promising responses, but the latter
      responses with PALA were not substantiated in randomized multicenter trials.
      Leucovorin enhances the cytotoxic activity of 5-FU in vitro and in vivo, and
      several clinical trials have shown improved response rates and possible trends in
      improved survival when such therapy is compared with the use of 5-FU as a single
      agent. More recent randomized trials have focused their attention on determining
      the optimal dose and schedule with this combination for producing a better
      clinical response with minimal toxicity. Schedules using infusional 5-FU appear
      to be the most active regimens when 5-FU is used as a single agent, as
      demonstrated by recent randomized trials. The Southwest Oncology Group (SWOG) and
      the Eastern Cooperative Oncology Group (ECOG) have performed separate randomized
      trials and have shown that the optimal regimens employ infusional 5-FU as a
      single agent, and that these are the least toxic regimens, perhaps more
      effective, and associated with a better quality of life. Future studies will
      focus on infusional regimens involving either short-term, high-dose protracted or
      long-term, low-dose protracted infusion of 5-FU, since these regimens have shown
      the most favorable toxicity spectrum and produced the longest survival times.
      Future research will also focus on the evaluation of various methods of delivery
      of 5-FU, including oral administration of the drug in combination with compounds
      that can modify its catabolism.

PMID- 9589034
TI  - The morphogenetic role of cadherin cell adhesion molecules in human cancer: a
      thematic review.

PMID- 9589035
TI  - Impact of antimicrobial use on the epidemiology of nosocomial infections on the
      oncology ward: implications for infection control.

PMID- 9589036
TI  - Gene transfer and the treatment of childhood cancer.

PMID- 9589037
TI  - Cancer metastasis: a search for therapeutic inhibition.
AB  - Failure of cancer treatment is often due to the growth of secondary, metastatic
      lesions in distant organs. Because initiation of metastasis is an early event in
      malignancy, patients often present not only with a primary tumor but also with
      occult metastases. Treatment of these metastases requires aggressive, systemic
      chemotherapy, since surgical removal of all metastatic foci is normally not
      feasible. However, drug toxicity caused by many of the currently used anticancer
      agents often limits chemotherapeutic approaches to malignant disease. In
      contrast, the development and use of novel cytostatic, antimetastatic agents
      could be less toxic and more applicable for long-term treatment in combating
      latent and/or residual disease. Practical intervention with such nontoxic agents
      has been envisioned as maintenance therapy after cytoreduction of a tumor or as a
      prophylactic treatment after the removal of a precancerous tumor exhibiting a
      genetic predisposition to a carcinomatous state. In this review, we discuss
      targets of the metastatic cell that may be potentially exploitable with
      chemotherapy, and present the current status of several novel, antimetastatic
      agents. Clinical evaluation of such agents will require new and appropriate
      clinical models for evaluating their antimetastatic efficacy. The recent
      successes achieved with certain proteinase inhibitors for the treatment of cancer
      are paving the way for the development of other therapeutic agents of this type,
      aimed at unique biochemical pathways associated with oncogenic behavior.

PMID- 9589038
TI  - Alterations in total iron, zinc, and calcium levels and their influence on the
      hepatic activities of gamma-glutamyl transferase and glucose-6-phosphatase in the
      host bearing transplantable murine lymphoma.

PMID- 9589039
TI  - Improving 5-fluorouracil: biomodulation, pharmacomodulation, or infusional
      administration schedules?

PMID- 9589040
TI  - Incurable breast cancer and long-term survival: anecdotes toward a new paradigm.

PMID- 9589041
TI  - [Analysis of drug-induced apoptosis in human leukemic cell line (HL-60)].
AB  - Cell death plays an essential role in cell homeostasis and the pathological
      process in cancer. Apoptosis has been identified by the internucleosomal DNA
      cleavage which appears to be associated with endonuclease activation. Proteolysis
      is considered to be an early event in apoptosis. We studied the effects of
      proteolysis on early apoptotic events, such as chromatin condensation, nuclear
      breakdown, DNA breakage and sensitivity to denaturation induced by anticancer
      drugs (camptothecin: CAM, 5-azacytidine: AZA) on HL-60 cells. CAM induced
      apoptosis on S phase and AZA on G1 phase. The internucleosomal DNA cleavage shown
      by both the presence of DNA fragments during gel electrophoresis and a large
      number of in situ DNA strands breaks (revealed in high intensity fluorescence
      FITC of cells in the TdT reaction) was prevented by the protease inhibitor, TPCK
      (N-tosyl-L-phenylalanine chlorometyl-ketone), as well as by an inhibitor of the
      apoptosis-associated endonuclease, ZnSO4. The protective effects were observed
      under conditions in which apoptosis was induced by agents with a different
      mechanism of action, such as the DNA damaging drug. CAM (topo-isomerase
      inhibitor), and an RNA antimetabolite, AZA. The protease inhibitor inhibits early
      events of apoptosis such as chromatin condensation, nuclear breakdown, DNA
      breakage and sensitivity to denaturation, which have different structures and a
      different mechanism of interaction with drugs. The results suggest that control
      of protease inhibitor may be a useful strategy to treat cancers.

PMID- 9589042
TI  - [p53 and Bax protein expression as predictor of chemotherapeutic effect in
      gastric carcinoma].
AB  - This study was performed to estimate p53 and Bax overexpression as a predictor of
      the response to chemotherapy of patients with gastric cancer. The subjects were
      20 patients with stage IV gastric cancer and 3 with locally recurrent lesions
      treated with 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) for 4 weeks. Of
      the total 23 patients, there were 10 responders: 2 showing complete response (CR)
      and 8, partial response (PR). Carcinoma biopsy specimens of all were obtained
      endoscopically with anti-p53 and anti-Bax antibodies. Of the 10 responders, 7
      were in the negative p53 staining group, while of the 13 non-responders, 11 were
      in the positive p53 staining group (p = 0.013). But no correlation was
      demonstrated between the chemotherapeutic effect and Bax staining alone.
      Moreover, among the p-53-positive cases, the patients with Bax-negative tumors
      were all chemoresistant. Therefore, immunohistochemical identification of p-53
      and Bax prior to chemotherapy may be a useful predictor for choice of non
      responders to chemotherapy.

PMID- 9589044
TI  - [Immunohistochemical study on the progression of colorectal cancer--with respect
      to apoptotic index, expression of apoptosis-related gene products, and labeling
      index of proliferating cell nuclear antigen (PCNA)].
AB  - To clarify the biological changes in the development and progression of
      colorectal cancer, immunohistochemical examination was performed with a
      particular focus on the activity of apoptosis, the expression of apoptosis
      related gene products and cell proliferation activity, assessed by the labeling
      index of proliferating cell nuclear antigen (PCNA). Seventy-six resected
      specimens of colorectal cancer were used to investigate the expression of
      apoptosis-related gene products, Bcl-2 protein and PCNA labeling index, as well
      as the apoptotic index using the TUNEL method. Seventy-five percent of 60
      advanced cancer specimens was negative for Bcl-2 protein, and the proportion was
      higher than that in early cancer specimens. The apoptotic index (AI) in the
      advanced cancers was significantly higher than in the early stage of cancers.
      Meanwhile, the percentage of PCNA-positive cells for the advanced cancers was
      significantly higher than for early cancer. This study demonstrated a decrease in
      Bcl-2 protein expression, an increase in tumor cell apoptosis, and opposite an
      increase of cellular proliferation activity in the progression of colon cancer
      from early to the advanced stage of the disease.

PMID- 9589043
TI  - [Enhanced induction of apoptosis of human colorectal cancer cells after
      preoperative treatment with 5-fluorouracil its relationship to DNA ploidy
      pattern].
AB  - We examined the relationship between apoptosis induced by 5-fluorouracil (5-FU)
      that was given preoperatively to colorectal cancer patients and DNA ploidy
      pattern, and investigated the cell cycle changes, and the expression of Ki-67.
      Twenty-nine patients with advanced colorectal cancer were divided into four
      groups, 3 days, 5 days, 7 days, and 10 days. Groups received continuous
      intravenous 5-FU at 500 mg/body/day preoperatively. Then, patients were divided
      into two groups by DNA ploidy pattern, diploid(D) and aneuploid(A). Apoptotic
      cells were stained by the terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling (TUNEL) method. The expression of Ki-67 was examined by
      immunohistochemical staining. We used flow cytometry (FCM) for analysis of cell
      cycle distribution. Apoptosis of cancer cells was mostly increased in 7 days 5-FU
      administration in both D and A groups. The expression of Ki-67 was reduced
      according to the prolongation of the term of 5-FU administration in both D and A
      groups. We assessed S-phase fraction (SPF) to evaluate the cell cycle changes by
      5-FU. Tumor samples of all patients after injection of 5-FU showed S-phase
      accumulation. The ratio of SPF (after 5-FU/before 5-FU) was the highest in the 5
      day 5-FU administration group in both D and A groups. We concluded that apoptosis
      and S-phase accumulation were increased, and proliferative activity was decreased
      by preoperative 5-FU administration in colorectal cancer patients. However, there
      was no clear correlation between DNA ploidy pattern and these changes.

PMID- 9589045
TI  - [Correlation between apoptotic index, bcl-2 protein expression and progression
      and prognosis in breast carcinoma].
AB  - Apoptosis is considered to play a critical role in tumorigenesis. It has been
      shown that apoptosis is controlled by both pro-oncogenes bcl-2, c-myc and tumor
      suppressor genes p53. We determined the apoptotic index (AI) on light microscopy
      and detected immunohistochemically the expression of bcl-2 and p53 in patients
      with breast cancer. The correlations between AI and clinicopathological factors,
      bcl-2 and p53 were also analyzed. Our results showed that bcl-2 expression was
      down-regulated in the process from normal breast epithelial cells to intraductal
      carcinoma and from intraductal carcinoma to invasive carcinoma. We failed to
      detect p53 protein in normal breast epithelial cells, and p53 positivity was 24%
      and 30% in intraductal and invasive cancer tissues, respectively. Moreover, AI
      was significantly associated with histological grade, mitotic index, and bcl-2
      and p53 expression. In univariate analyses, lower AI and bcl-2 expression was
      significantly predictive of a better prognosis for both disease-free survival and
      overall survival. These results suggest that apoptosis and apoptosis-related gene
      (bcl-2, p53) are related to progression and prognosis in breast cancer.

PMID- 9589046
TI  - [Long-term survival in terms of DNA-RNA contents in breast cancer].
AB  - Fifty-nine primary breast cancers were analyzed by flow cytometric cellular DNa
      RNA contents stained by acridine orange simultaneous DNA-RNA double staining.
      Forty-three cases (72.9%) out of 59 had abnormal stemlines (DNA aneuploidy), and
      16 normal ones (DNA diploidy). RNA indices widely ranged from 1.41 to 9.02
      (2.99). There was no correlation between DNA indices and RNA indices. The
      patients with DNA diploidy had a better prognosis than those with DNA aneuploidy,
      but the differences were not significant. The patients with a high RNA index of
      more than 4.0 had a significantly poorer prognosis than those with an index of
      less than 4.0. Those results suggest that RNA contents, and DNA contents are
      independent prognostic factors, and especially RNA contents may be a good
      prognostic factor in long-term survival in breast cancer.

PMID- 9589047
TI  - [Prognostic significance of loss of heterozygosity in breast cancer].
AB  - Loss of heterozygosity (LOH) was analyzed in 113 cases of sporadic breast cancer
      using 35 microsatellite markers on 20 chromosomes. LOH was frequently seen in 17p
      (44%), 16q (31%), 17q (29%) and 13q (23%). Individual patients were scored
      according to the incidence of LOH at the above four chromosomal markers; with no
      LOH as 1, with one or two LOH as 2, and with three of four LOH as 3. A high LOH
      score was well associated with high histological grade (p = 0.019) and a
      significantly poor prognosis (p = 0.0035). These data suggest that accumulation
      of LOH occurs at a later stage of breast cancer progression, and that the LOH
      score may be a useful prognostic marker of breast cancer.

PMID- 9589048
TI  - [Relationship between DNA ploidy and survival in breast cancer].
AB  - The DNA ploidy pattern from fresh frozen specimens and survival rate was
      investigated in 91 primary breast cancers. Diploid patterns were found in 32
      (35.2%) and aneuploid patterns in 59 (64.8%). The 5-year overall survival rate
      was significantly lower in aneuploid cases (76.3%) than diploid cases (93.8%) (p
      = 0.042), while there was no significant difference in disease-free survival
      between the two groups. there were negative nodes, no significant differences in
      5-year overall or disease-free survival between patients with diploidy and
      aneuploidy. In contrast, when there were positive nodes, the 5-year overall and
      disease-free survival rates in patients with aneuploidy were 60.6% and 48.5%,
      which were significantly lower (p = 0.048 and p = 0.030) than the corresponding
      percentages of 92.3% and 84.6%, in those with diploidy. When the ploidy pattern
      was compared with other factors, a very close correlation was found between the
      ploidy pattern and histological grading (p < 0.0001). The ploidy pattern
      determined by flow cytometric DNA analysis may reflect the grade of malignancy of
      the breast cancer.

PMID- 9589049
TI  - [A new microsatellite instability analysis using fluorescent primers and laser
      scanning].
AB  - To demonstrate the instability of microsatellite sequences, which have been
      linked to DNA mismatch repair deficiency and indicate a high risk of
      carcinogenesis, polymerase chain reaction (PCR) and electrophoretic analysis have
      been used. However, the electrophoretic profiles of PCR-amplified microsatellite
      sequences are often too complicated, and the conventional method using
      autoradiography has critical problems in detection characteristics and migration
      accuracy. First, we made use of fluorescence-labeled PCR and laser scanning to
      detect bands quantitatively. Second, we characterized Taq polymerase-dependent
      modification of the amplified microsatellite sequences and optimized the
      electrophoretic profiles by enzymatic modification with T4 DNA polymerase. Third,
      we developed a dual fluorescence co-electrophoresis system, in which both samples
      derived from cancer and normal tissues are electrophoresed in the same lane, in
      order to minimize migration errors. Furthermore, we classified all of the
      observed patterns of microsatellite alteration and set up new criteria for
      assessing microsatellite instability. Using the system developed here and the
      criteria we proposed, a precise judgment can be made and rates of positivity in
      various human malignancies may be corrected.

PMID- 9589050
TI  - [Analysis of microsatellite alteration in colorectal cancer].
AB  - We investigated the possible correlation between the microsatellite alterations
      (replication error: RER, and loss of heterozygosity: LOH) and clinicopathologic
      factors and survival in colorectal cancer. A total of 78 colorectal cancers was
      examined for microsatellite alteration at three microsatellite loci containing
      D2S123, D18S58 and C117-703. RER is considered positive when at least one
      microsatellite locus is detected. RER was positive in 28.2%, and the respective
      positivity was 12.8%, 15.3% and 11.5%. The positivity of LOH was 6.4%, 10.3% and
      19.2%, in that order. RER-positive cancers were more significantly found in the
      proximal colon than the distal colorectum. Node-negative colorectal cancers were
      more noted in RER (+)-positive cancers. Multivariate analysis showed that LOH in
      D18S58 locus and RER in CI17-703 locus were independent prognostic factors.

PMID- 9589051
TI  - [Effect of low-dose CDDP/5-FU therapy on thymidylate synthase content].
AB  - Low-dose therapy consisting of cisplatin plus 5-fluorouracil was given to 20
      patients with advanced gastric cancer, and specimens were obtained to evaluate
      levels of 5-fluorodeoxyuridine (FdUMP) and thymidylate synthase (TS), indices of
      DNA, and proliferating nuclear cell antigen (PCNA). There was a significant
      correlation between the levels of FdUMP, total TS and free TS in cancer and in
      normal gastric mucosa, respectively. Total TS of cancer was higher than that of
      normal tissue, at 5.3 +/- 4.8 and 3.4 +/- 2.2 pmol/g, respectively. On the other
      hand, there was no relationship nor difference between The TSIR ratio of cancer
      and normal mucosa. The FdUMP levels of far advanced cancer showed a tendency to
      be lower than those of the less advanced one, especially in liver metastasis. The
      total TS was higher in intestinal type and in INF alpha or beta. The free TS was
      higher in invasive type, liver metastasis and curability C. The TSIR ratio showed
      a tendency to be lower in far advanced cases, such as invasive type and INF
      gamma. The correlation between DNA index and TS values and between PCNA labeling
      index and TS values were good. These results suggest that TS levels would be a
      predictor for malignant potential as well as for chemosensitivity.

PMID- 9589052
TI  - [Toremifene sensitized the effect of adriamycin on human breast cancer cell
      lines].
AB  - A experimental study was reported here to clarify the chemosensitizing effect of
      Toremifene (Tor) on human breast cancer cell lines. MCF7, estrogen dependent
      adriamycin (ADM) resistant cell, and MDA-MB231, estrogen independent cell, were
      preincubated for 8 hours with Tor 0, 4 or 10 microM, then with ADM 0-10
      micrograms/ml for one hour. After that, cells were cultured for 24 hours, and
      their cell cycle and growth were analyzed with flow-cytometry and MTT assay,
      respectively. Furthermore, the ADM concentrations of these cells were measured by
      high-performance liquid chromatographic assay (HPLC). Although flowcytometric
      analysis showed the enhancement of Gz block only in MCF7 at the ADM concentration
      with 5 micrograms/ml, the sensitizing effect was revealed by MTT assay, and the
      elevation of ADM concentration was found in HPLC assay in both cells. The
      chemosensitizing effect of Toremifene was observed in estrogen dependent and
      independent cell lines.

PMID- 9589053
TI  - [Frequent loss of heterozygosity on the long arm of chromosome 21 in human
      esophageal, squamous cell carcinoma].
AB  - We investigated human esophageal squamous cell carcinoma using microsatellite
      markers on the long arm of chromosome 21 (21q) and found frequent loss of
      heterozygosity (LOH). The frequency of LOH was more than 50% in most of the
      microsatellite markers examined. Whole chromosome deletion suspected cases were
      observed in 25% of all cases. No case with microsatellite instability was found.
      Three common regions of allelic loss were identified. The frequent LOH was
      observed from early stage in pTNM classification. An unknown tumor suppressor
      gene in the genesis of esophageal squamous cell carcinoma may exist in 21q.

PMID- 9589054
TI  - [Serum carcinoembryonic antigen doubling time in patients with recurrent
      gastrointestinal carcinoma and its relationship to tumor biology and life
      expectancy].
AB  - BACKGROUND: The present study was done to determine if carcinoembryonic antigen
      (CEA) concentration doubling time can predict the course of disease in patients
      with adenocarcinoma of the gastrointestinal tract and characterize tumor biology.
      METHODS: CEA doubling times were determined from semilogarithmic plots of CEA
      concentration time courses in 20 patients with recurrent gastric cancer and 17
      with recurrent colorectal cancer. RESULTS: Gastric and colorectal carcinomas
      showed mean CEA doubling times of 229 days and 85 days, respectively. There were
      no significant differences with regard to patient age, tumor size, gross
      appearance and histological differentiation. However, women had shorter CEA
      doubling times than did men. Flow cytometric analysis showed that tumors with a
      higher proportion of cells in S-phase (> or = 15%) had significantly shorter CEA
      doubling times than those with a lower S-phase fraction (< 15%). There was a
      significant correlation between the CEA doubling time and the length of survival
      after the initial CEA concentration increase in patients with recurrent gastric
      and colorectal carcinomas. CONCLUSIONS: CEA doubling time predicts life
      expectancy in patients with adenocarcinoma of the gastrointestinal tract.
      Differences in survival time are closely associated with variations in the
      biological aggressiveness of individual tumors.

PMID- 9589055
TI  - [Telomerase activity in colorectal cancer--a semi-quantitative procedure].
AB  - Telomerase maintains telomere at the end of chromosome and stabilizes chromosome.
      It is thought to have important roles in cancer progression and cell immortality.
      We evaluated the role of telomerase expression in colorectal carcinogenesis.
      Materials included 13 colonic adenomas, 9 early colorectal cancers, 32 advanced
      colorectal cancers, 5 metastatic tumors, and 30 non-cancerous colon mucosas. The
      telomerase activity was analyzed using TRAP-eze (Oncor Inc.) for a semi
      quantitative method. The positive rate of telomerase activity was 13.3% in non
      cancerous colonic mucosa, 15.4% in colonic adenomas, 77.8% in early colorectal
      cancers, 93.8% in advanced colorectal cancers, and 100% in metastatic tumors; the
      mean value was 18.0, 29.9, 65.8, 97.0 and 161.3. The correlation between
      telomerase activity and tumor size, histologic type, or depth of invasion was
      noted. Sensitivity, specificity and accuracy were on the order of 89%, 98% and
      93% at the cut-off level as two times the mean value of non-cancerous mucosa.
      Telomerase had an important role in carcinogenesis, and progression of colorectal
      cancer, and it was suggested to be useful for a tumor marker.

PMID- 9589056
TI  - [Analysis for predicting the prognostic factors of gastrointestinal tract
      leiomyosarcoma using MIB-1 and DNA flow cytometry].
AB  - PURPOSE: The present study was undertaken to investigate the possibility of
      determining a prognosis for gastrointestinal tract leiomyosarcoma with the use of
      DNA analysis and MIB-1 staining. SUBJECTS AND METHODS: Malignant tumors
      originating in smooth muscle of the gastrointestinal tract, surgically excised
      from 23 lesions in 17 patients (stomach; 8 cases, 12 lesions; small intestine: 6
      cases, 8 lesions; colon: 3 cases, 3 lesions) and embedded in paraffin, were
      examined. DNA was analyzed using flow cytometry to produce a DNA histogram, and
      aneuploidy and diploidy were found. MIB-1 staining was done in conformity with
      the ABC method. RESULTS: 1. An investigation of prognoses using the Kaplan-Meier
      method revealed a tendency for more favorable prognoses in patients determined to
      be aneuploid through DNA analysis. However, this was not significantly better
      than those exhibiting diploidy. 2. All patients who died had a MIB-1 staining
      positivity rate of over 10%, while all patients who had no recurrence within one
      year or survived had a MIB-1 staining positivity of less than 10%. 3. No
      consistent trends were observed between MIB-1 positivity rate and DNA analysis,
      MIB-1 positivity rate and size of tumor, or DNA analysis and size of tumor. 4.
      The MIB-1 positivity rate of patients with remote metastases was significantly
      greater than that of patients with no remote metastases. CONCLUSION: From the
      fact that patients with MIB-1 positivity rates of greater than 10% had a poor
      prognosis, while those with rates of less than 10% had a favorable prognosis, we
      conclude that a MIB-1 positivity rate of 10% is an important value in determining
      the prognosis of patients with gastrointestinal tract leiomyosarcomas.

PMID- 9589057
TI  - [Genetic testing for ret mutation for early diagnosis and treatment in familial
      medullary thyroid carcinoma: a case report].
AB  - A 13-year-old girl and her older sister were referred to our hospital because her
      father and another older sister and been suffering from medullary thyroid
      carcinoma (MTC). Physical examinations revealed no thyroid mass. Ultrasonography
      (US) detected a small hypoechoic lesion in the right thyroid lobe, 3 mm in size.
      The serum calcitonin level was slightly elevated for their age. One and half year
      later, US finding showed a slightly larger mass, 7 mm in size, which was not
      palpable. Genetic testing for ret protooncogene mutation revealed a point
      mutation at codon 634 (Cys-->Arg) in exon 11. Surgical treatment was recommended,
      however, the patient wanted to receive it only after the admission to senior high
      school. Her sister had no mutation in ret protooncogene. The patient underwent
      total thyroidectomy with modified neck dissection at 16 years of age. At that
      time, a new mass emerged in the left thyroid lobe and the serum calcitonin level
      increased to 171 pg/ml. MTC was found in each lobe with positive staining of CEA
      and carcitonin. No lymph node metasis was found. Her postoperative course was
      uneventful. Genetic testing for ret mutation is effective for early diagnosis and
      treatment of patient with FMTC, and is recommended as standard management for
      hereditary MTC in affected families.

PMID- 9589058
TI  - [Nuclear DNA content of parathyroid tumor with hyperparathyroidism].
AB  - It is not easy to make a differential diagnosis among adenoma, hyperplasia and
      carcinoma with hyperparathyroidism (HPT). We investigated the flowcytometric
      nuclear DNA content and analysis of cell cycle for 29 patients (39 parathyroid
      glands) with HPT and 16 normal parathyroid glands at the Department of Surgery
      II, Fukushima Medical College. Flowcytometry was performed by EPICS 751
      flowcytometer (Coulter Co.) in paraffin-embedded tissue. Each fraction of cell
      cycle was analyzed by the PARAI software program. All controls and secondary
      hyperplasia showed diploid. Aneuploid pattern was found in 27.6% of all HPTs (50%
      of carcinomas, 30% of adenomas and 6.7% of primary hyperplasia). The S phase
      fraction (SPF) and proliferative index (PI) were increased in carcinomas. PIs,
      especially the fraction of G2M, in primary and secondary hyperplasias were more
      decreased than those in normal controls and adenomas. Preoperative intact-PTH, c
      PTH, ionized calcium, ALP and weight of parathyroid gland had no significant
      correlation with DNA ploidy, DNA index and SPF. PI had tended to correlate only
      with the weight of parathyroid gland. When DNA content shows aneuploid, high SPF
      or PI in parathyroid adenoma and hyperplasia, strict follow-up is required
      because of the malignant potential. If G2M or PI is lower, we should pay
      attention not to leave any remaining glands in parathyroidectomy in the light of
      hyperplasia.

PMID- 9589061
TI  - UCH9, a new antitumor antibiotic produced by Streptomyces. II. Structure
      elucidation of UCH9 by mass and NMR spectroscopy.
AB  - The structure of UCH9, which is a novel antitumor agent, was determined by
      spectroscopic methods. UCH9 consists of an aglycone and five 2,6-dideoxy sugars
      (three D-olivoses, one 4-O-methyl-D-olivose and one D-oliose). Four of the five
      sugars are sequentially connected through a beta 1-->3 linkage (olivose-1-->3-4-O
      methyl-olivose-1-->3-oliose-1-->3-+ ++olivose). On the basis of the results of
      spectroscopic analysis, it was found that UCH9 belongs to the aureolic acid
      family of antibiotics. The structure of UCH9 is unique in that mono- and
      tetrasaccharide moieties, and a long hydrophobic side chain (sec-butyl group) are
      attached to the aglycone, while di- and trisaccharide moieties and a methyl or a
      hydrogen are attached in the case of the known aureolic acid analogs. It is known
      that aureolic acid analogs from a dimer in the presence of Mg2+. NMR, FAB-MS and
      atomic absorption analysis revealed that UCH9 isolated from Streptomyces also
      forms a dimer, containing one equivalent molar Mg2+.

PMID- 9589060
TI  - UCH9, a new antitumor antibiotic produced by Streptomyces: I. Producing organism,
      fermentation, isolation and biological activities.
AB  - We developed a microbial prescreen using Bacillus stearothermophilus NUB3620 and
      bacteriophage TP-68 to detect potential antitumor compounds acting on DNA or
      topoisomerases. During the course of screening microbial cultures for their
      antibacteriophage activities, we found that Streptomyces sp. isolated from a soil
      sample collected in Iwakuni city, Yamaguchi prefecture, Japan, produced a new
      antitumor antibiotic, UCH9. UCH9 was isolated from culture broth by a combination
      of EtOAc extraction and column chromatography. UCH9 has a new structure related
      to the antitumor antibiotic chromomycins. It exhibited antimicrobial activity
      against Gram-positive organisms. UCH9 also showed cytotoxic activity against HeLa
      S3 cells with an IC50 value of 13 nM and exhibited antitumor activity in vivo
      against mouse leukemia P388.

PMID- 9589059
TI  - Epostatin, new inhibitor of dipeptidyl peptidase II, produced by Streptomyces sp.
      MJ995-OF5. I. Taxonomy of producing strain, fermentation, isolation, physico
      chemical properties and biological properties.
AB  - A new inhibitor of dipeptidyl peptidase II (DPP-II, EC 3.4.14.2), designated as
      epostatin, was discovered in the fermentation broth of a strain isolated in our
      institute. The strain has been identified as Streptomyces sp. MJ995-OF5 on the
      basis of taxonomic studies. Epostatin was obtained as a yellow powder after
      seqential purification by chromatography on Diaion HP-20, n-butanol extraction,
      Sephadex LH-20 column chromatography and centrifugal partition chromatography
      (CPC). Epostatin inhibited DPP-II competitively in a dose dependent manner. The
      compound was slightly inhibitory against other dipeptidyl peptidases.

PMID- 9589062
TI  - Cystothiazoles A and B, new bithiazole-type antibiotics from the myxobacterium
      Cystobacter fuscus.
AB  - New bithiazole-type antibiotics, cystothiazoles A (C20H26N2O4S2) and B
      (C20H26N2O5S2), have been isolated from a culture broth of the myxobacterium,
      Cystobacter fuscus. The gross structures of these compounds were elucidated by
      spectroscopic analysis, and their absolute stereochemistry was determined by
      chemical degradation of cystothiazole A. Cystothiazole A inhibits fungi and human
      tumor cells, whereas it is inactive against bacteria. The antifungal activity
      appears to result from the inhibition of submitochondrial NADH oxidation.
      Although these compounds are structurally related to the known antibiotic
      myxothiazol, cystothiazole A was more active against fungi and less cytotoxic
      than myxothiazol.

PMID- 9589063
TI  - Isolation and characterization of a new pyrano[4',3':6,7]naphtho[1,2-b]xanthene
      antibiotic FD-594.
AB  - During our screening of microbial metabolites for effective drugs against tumor
      cell lines, we discovered a new pyrano[4',3':6,7]naphtho[1,2-b]xanthene
      derivative, FD-594 from the fermentation broth of Streptomyces sp. TA-0256. FD
      594 shows moderate activity against tumor cell lines, comparative to that of
      adriamycin, as well as antibacterial activity against some Gram-positive
      bacteria.

PMID- 9589065
TI  - Cell wall active antifungal compounds produced by the marine fungus hypoxylon
      oceanicum LL-15G256. I. Taxonomy and fermentation.
AB  - The cell wall targeted antifungal activity of Hypoxylon oceanicum LL-15G256
      extracts resulted from the production of novel lipodepsipeptides and previously
      reported macrocyclic polylactones. In an optimized medium, titers of the
      lipodepsipeptide and the polylactones reached approximately 200-400 mg/liter and
      25-50 mg/liter, respectively. The optimum fermentation temperature for production
      of 15G256 gamma was 28 degrees C. Seawater appeared to have an inhibitory effect
      on metabolite accumulation at lower fermentation temperatures.

PMID- 9589066
TI  - Cell wall active antifungal compounds produced by the marine fungus Hypoxylon
      oceanicum LL-15G256. II. Isolation and structure determination.
AB  - Fermentations of the marine fungus Hypoxylon oceanicum (LL-15G256) were found to
      have potent antifungal activity. Isolation and purification of the antifungal
      agents provided two classes of compounds, macrocyclic polylactones and the
      lipodepsipeptides 15G256 gamma (1), 15G256 delta (2) and 15G256 epsilon (3). The
      isolation and structure elucidation of the lipodepsipeptides, all containing D
      glutamate, L-serine, and the rare amino acid beta-ketotryptohan, are described in
      this paper.

PMID- 9589064
TI  - Structure and biosynthesis of FD-594; a new antitumor antibiotic.
AB  - The structure of a novel antitumor antibiotics FD-594 (1), produced by
      Streptomyces sp. TA-0256, was determined to have a glycosylated
      pyrano[4',3':6,7]naphtho[1,2-b]-xanthene skeleton by means of spectral data. The
      biosynthetic studies of the chromophore of 1 was also carried out by feeding
      experiments with [1-13C]-, [2-13C]-, and [1,2-13C2]sodium acetate. The labeling
      pattern was determined by 13C NMR including 2D INADEQUATE experiments, which
      allowed us to elucidate that the chromophore of 1 is derived from 14 acetate,
      followed by the loss of one carbon atom.

PMID- 9589067
TI  - Cell wall active antifungal compounds produced by the marine fungus Hypoxylon
      oceanicum LL-15G256. III. Biological properties of 15G256 gamma.
AB  - 15G256 gamma is a cyclic lipopeptide antifungal agent discovered in a mechanism
      of action screen for cell wall acting antifungal agents. The compound shows
      moderate activity in both greenhouse tests against plant disease caused by
      pathogenic fungi and in in vitro tests against human fungal pathogens.
      Microscopic examination of treated fungi suggests that the compound acts by the
      inhibition of cell wall biosynthesis. However, in vitro inhibition of Neurospora
      crassa glucan and chitin synthase were only observed at high drug concentrations
      suggesting that 15G256 gamma may act on a novel cell wall target.

PMID- 9589068
TI  - Micacocidin A, B and C, novel antimycoplasma agents from Pseudomonas sp. I.
      Taxonomy, fermentation, isolation, physico-chemical properties and biological
      activities.
AB  - A Gram-negative bacterium was found to produce a new zinc-containing antibiotics,
      micacocidin A and related compounds containing Cu or Fe, micacocidin B and C,
      respectively. These antibiotics were isolated by column chromatography on silica
      gel, and then separated by preparative TLC and HPLC. These new antibiotics
      exhibited an excellent activity against Mycoplasma species. The producing
      bacterium was characterized and ascribed to the genus Pseudomonas.

PMID- 9589069
TI  - Micacocidin A, B and C, novel antimycoplasma agents from Pseudomonas sp. II.
      Structure elucidation.
AB  - Metal-containing novel heterocyclic antibiotics, micacocidin A (1), B (2), and C
      (3) have been isolated from the culture filtrate of Pseudomonas sp. No. 57-250.
      The structure and absolute configuration of micacocidin A, an octahedral Zn2+
      complex, was determined by X-ray crystallographic analysis. And then, the
      structures of the two congeners, micacocidin B (Cu2+ complex) and C (Fe3+
      complex) were investigated by employing one dimensional and two dimensional
      homonuclear and heteronuclear NMR spectroscopies and mass spectrometry.

PMID- 9589070
TI  - Anthranilamides: new antimicroalgal active substances from a marine Streptomyces
      sp.
AB  - 2-[Methyl-(3-phenylpropionyl)amino]-benzoic acid (1e) was isolated from a culture
      of marine Streptomyces sp. strain B7747. Analogous compounds have potential
      importance as phytotoxic substances, hence compound 1e and the analogues 1a
      approximately 1d and 1f approximately 3a were synthesised. Antimicroalgal
      activity of the anthranilamide analogues showed that esters 1b, 1f and 2b were
      more active than the free acids. The minimum inhibitory concentration (MIC)
      against Chlorella vulgaris, Chlorella sorokiniana, Chlorella salina and
      Scenedesmus subspicatus ranged from 20 to 107 micrograms/ml. All anthranilamides
      were inactive against Staphylococcus aureus, Escherichia coli, and Mucor miehei.

PMID- 9589071
TI  - A 7.6kb DNA region from Streptomyces kasugaensis M338-M1 includes some genes
      responsible for kasugamycin biosynthesis.
AB  - A 7.6kb PstI-KpnI DNA fragment including a sequence highly similar to kasugamycin
      acetyltransferase gene (kac) was isolated from Streptomyces kasugaensis M338-M1
      and sequenced. Nine open reading frames (ORFs), designated as ORF A, B, C, D, E,
      F, G, H and I, were recognized in this region, although ORF A was incomplete. ORF
      G runs in the opposite direction to the others. The amino acid sequence deduced
      from ORF H showed 98% similarity to that of the kasugamycin acetyltransferase
      from S. kasugaensis MB273-C4, another kasugamycin (KSM) producer. Transformation
      of E. coli JM109 with ORF H made the strain highly resistant to KSM. The deduced
      amino acid sequences of the ORF A, C and D products were similar, respectively,
      to glucosyltransferase I from E. coli (26%), beta-alanine: pyruvate transaminase
      from Pseudomonas putida (32%) and dTDP-D-glucose 4,6-dehydratase (StrE) from
      Streptomyces griseus (37%). The strE-like ORF (ORF D) seems to be the gene
      responsible for formation of the 6-deoxy structure of the kasugamine moiety. ORF
      A and ORF C are also likely to have roles in KSM biosynthesis. Taken together,
      our analyses strongly suggest that this DNA region includes at least a part of
      the gene cluster of KSM biosynthesis.

PMID- 9589072
TI  - Aureobasidins as new inhibitors of P-glycoprotein in multidrug resistant tumor
      cells.
AB  - Cyclic depsipeptide antibiotic aureobasidin A (AbA) and its analogs were tested
      for the inhibitory activity of P-glycoprotein in multidrug resistant cancer cells
      as well as for the antifungal activity. Some analogs with lower antifungal
      activity than AbA showed higher inhibition of P-glycoproteins indicating
      difference of the structure-activity relationships between the two activities.
      Among AbA analogs tested, [D-beta-hydroxy-methylvalyl9]-AbA newly prepared by
      chemical synthesis, which had much lower antifungal activity than AbA, showed 10
      fold higher inhibitory activity of P-glycoprotein than AbA.

PMID- 9589073
TI  - Syntheses of antifungal aureobasidin A analogs with alkyl chains for structure
      activity relationship.
AB  - The syntheses of aureobasidin A (AbA) derivatives with alkyl chains and their in
      vitro structure-biological activity relationships are discussed. The analogs
      replaced at positions 6, 7, or 8 of AbA with either L-glutamic acid, delta
      hydroxy-L-norvaline, or delta-hydroxy-N-methyl-L-norvaline are prepared. The
      gamma-carboxyl or delta-hydroxyl group of these new amino acids was coupled with
      acids, alcohols, or amines with alkyl chains. While the analogs having L-glutamic
      acid residue at positions 6 or 8 showed weak activity, esterification of the
      gamma-carboxyl group with benzyl or shorter alkyl (C4 or C6) alcohols,
      significantly enhanced the activities. Introduction of longer alkyl (C14) chain
      to the same amino acids residues at positions 6, 7, or 8 resulted in total loss
      of antifungal activity. Among the lipophilic analogs in [L-Glu6] derivatives, the
      C6 alcohol ester showed the strongest antifungal activity against Candida spp. so
      far tested. None of the derivatives showed activity against Cryptococcus
      neoformans.

PMID- 9589074
TI  - Albocycline- and carbomycin-type macrolides, inhibitors of human prolyl
      endopeptidases.

PMID- 9589075
TI  - Epostatin, new inhibitor of dipeptidyl peptidase II, produced by streptomyces sp.
      MJ995-OF5 II. Structure elucidation.

PMID- 9589076
TI  - Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems II:
      2-alkyl and 2-arylthiomethyl derivatives.

PMID- 9589077
TI  - Synthesis and biological activity of quaternary ammoniopropenyl cephalosporins
      having two vinyl groups.

PMID- 9589078
TI  - Alnumycin a new naphthoquinone antibiotic produced by an endophytic Streptomyces
      sp.

PMID- 9589079
TI  - Synthesis and biological evaluation of the analogs of bioxanthracenes ES-242s, N
      methyl-D-aspartate antagonists.

PMID- 9589080
TI  - Intracranial ependymomas in children: a critical review of prognostic factors and
      a plea for cooperation.
AB  - BACKGROUND: Current controversies in pediatric intracranial ependymoma include
      histologic categorization and management. Most of our knowledge of this disease
      comes from single-institution reports. METHODS: A literature search was done,
      covering the period 1976-1996. The aim of this review is to analyze the
      prognostic factors reported in the literature over the last 20 years. RESULTS:
      Forty-five series were reviewed, including more than 1,400 children. The largest
      series reported on 92 patients, and the accrual rate ranged from 0.32-12 patients
      per year. None of the prognostic factors reported achieved a consensus throughout
      the different series. Histology remains a major issue, and the range in the
      incidence of anaplastic ependymo mas (7-89%) highlights the difficulty in
      agreeing on a histological grading system. The role of surgery on the outcome
      seems to be determinant. Recent series based on homogeneous imaging-documented
      extents of resection strongly support the benefit of postoperative radiotherapy.
      The lack of a proven, effective chemotherapy regimen precludes its use except in
      prospective pilot studies. CONCLUSIONS: Limited information is available from
      single-institution reports in ependymoma. Only large national or international
      studies can provide enough information to allow a multivariate analysis of the
      prognostic factors, and thus lead to new therapeutic proposals.

PMID- 9589081
TI  - Results of alternating chemotherapy and hyperfractionated radiation therapy in
      childhood rhabdomyosarcoma.
AB  - BACKGROUND: A regimen of multi-drug chemotherapy alternating with split course
      hyperfractionated radiation therapy (HFRT) was adopted for the treatment of
      patients with rhabdomyosarcoma (RMS). The purpose of this treatment regimen was
      to allow for the timely delivery of radiation and chemotherapy, reduce treatment
      related toxicity, and improve compliance. PROCEDURE: Forty-four patients with
      stages II-IV RMS were treated with HFRT and received 5,400 cGy. The treatment was
      administered in two courses (3,000 and 2,400 cGy) and separated by a 4-week
      interval. HFRT consisted of 150 cGy delivered twice a day, 5 days a week with an
      interfraction interval of 4-6 hours. A limited comparison was made between the
      HFRT patients and 42 historical patients with comparable clinical characteristics
      who were treated with similar chemotherapy and conventionally fractionated
      radiation therapy (CFRT) (median 4,800 cGy, range 4,000-5,680 cGy). RESULTS: HFRT
      patients completed radiation therapy in 59.1 +/- 9.4 days (mean +/- SD) and CFRT
      patients completed treatment in 56.6 +/- 10.5 days compared to an expected 52 and
      40 days, respectively. With a median follow-up of 55 months for the HFRT patients
      and 104 months for the CFRT patients, no differences in local control or survival
      were noted. Nine of 44 (21%) HFRT and 8/42 (19%) CFRT patients experienced local
      failure. The median time to local failure was 15 months for patients in the HFRT
      group and 11 months for patients in the CFRT group. CONCLUSIONS: The results of
      the HFRT regimen were acceptable in terms of toxicity and compliance. No
      improvement in local control was obtained by alternating radiation and
      chemotherapy. The lack of difference between patients treated with HFRT and CFRT
      may be related to the lengthened treatment time of the split course regimen, the
      small difference in total dose, and tumor repopulation.

PMID- 9589082
TI  - Engraftment after myeloablative doses of 131I-metaiodobenzylguanidine followed by
      autologous bone marrow transplantation for treatment of refractory neuroblastoma.
AB  - BACKGROUND: Metaiodobenzylguanidine (MIBG) labeled with 131I has been used for
      targeted radiotherapy of neural crest tumors, with bone marrow suppression being
      the primary dose-limiting toxicity. The purpose of this study was to examine the
      engraftment and toxicity of higher myeloablative doses of 131I-MIBG with
      autologous bone marrow support. PROCEDURE: Twelve patients with refractory
      neuroblastoma were given infusions of their autologous, cryopreserved bone marrow
      following 1-4 doses of 131I-MIBG. The median cumulative administered activity per
      kilogram of 131I-MIBG was 18.0 mCi/kg (range 14.1-50.2 mCi/kg), the median total
      activity was 594 mCi (range 195-1,353 mCi), and the median cumulative whole body
      irradiation from 131I-MIBG was 426 cGy (range 256-800 cGy). A median of 2.5 x
      10(8) viable cells/kg (range 0.9-4.7 x 10(8) cells/kg) was given in the bone
      marrow infusion. RESULTS: All 12 patients achieved an absolute neutrophil count >
      500/microliter with a median of 19 days, but only 5/11 evaluable patients
      achieved red cell transfusion independence, in a median of 44 days; and 4/11
      evaluable patients achieved platelet count > 20,000/microliter without
      transfusion, in a median of 27 days. CONCLUSIONS: Autologous bone marrow
      transplantation may allow complete hematopoietic reconstitution following
      ablative 131I-MIBG radiotherapy in patients with neuroblastoma. Risk factors for
      lack of red cell or platelet recovery include extensive prior chemotherapy,
      progressive disease at the time of transplant, especially in the bone marrow, and
      a history of prior myeloablative therapy with stem cell support.

PMID- 9589083
TI  - Impact of age and cranial irradiation on radiographic skeletal pathology in
      children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Symptomatic osteopenia is a common form of morbidity in children with
      acute lymphoblastic leukemia (ALL) before, during, and after treatment. A causal
      role for corticosteroids has been proposed, but other investigators have
      suggested that cranial irradiation is an important factor contributing to this
      disorder. PROCEDURE: In this study of children with ALL, all of whom received
      steroids, skeletal morbidity was assessed radiographically by an observer who was
      blinded to the ages of the children, their risk categorization (and related
      treatment), and the timing of the assessments with respect to the administration
      of therapy. DISCUSSION: Skeletal morbidity was most prevalent in older subjects
      who had been given cranial radiotherapy. However, there was no difference in the
      frequency of fractures in two groups of younger children (< or = 9 years of age),
      one irradiated and the other not. CONCLUSIONS: It is likely that corticosteroid
      therapy plays an important part in the pathogenesis of this disorder. The role
      played by cranial irradiation is much less certain.

PMID- 9589084
TI  - Growth and endocrinological disorders up to 21 years after treatment for acute
      lymphoblastic leukemia in childhood.
AB  - BACKGROUND: Our aim was to evaluate endocrinological status 10-21 years after
      treatment for childhood acute lymphoblastic leukemia (ALL) with chemotherapy (C)
      and cranial irradiation (C + I) or only C, and to correlate the endocrine data
      with growth parameters. PROCEDURE: Of 30 patients (15 females and 15 males), 18
      were treated with C + I and 12 were treated with C only. Height standard
      deviation score (HSDS) and body mass index standard deviation score (BMISDS)
      before treatment, at end of treatment, and at follow-up were calculated from
      height and weight registered from the charts. At follow-up examinations,
      provocative growth hormone (GH) tests (clonidine and insulin tolerance test) and
      an ACTH test were performed. Furthermore, blood samples for hormonal analysis,
      IGF-I, IGFBP-3, GHBP, and leptin were drawn. RESULTS: Eleven patients (9 treated
      with C + I and 2 treated with C) showed insufficient response to GH tests. Two
      patients had hypogonadism. HSDS and IGF-I were significantly lower and GHBP
      significantly higher in GH-deficient patients compared to the group with normal
      GH secretion at follow-up. BMISDS steadily increased from start of treatment
      until follow-up, independent of GH status at follow-up. BMISDS at follow-up was
      positively correlated with serum leptin (P < 0.001), and serum leptin was
      significantly higher in the cranial irradiated group as compared to the
      nonirradiated group. CONCLUSIONS: GH deficiency is frequently found at long-term
      follow-up in patients treated for childhood ALL. Other hormonal deficiencies are
      rare. HSDS at long-term follow-up is dependent on GH secretory status. Long-term
      endocrinological follow-up examinations in patients treated for childhood ALL are
      recommended, as hormonal replacement therapy may be indicated.

PMID- 9589085
TI  - Peripheral primitive neuroectodermal tumor presenting with diffuse cutaneous
      involvement and 7;22 translocation.
AB  - We report an unusual case of peripheral primitive neuroectodermal tumor (pPNET)
      in an infant presenting with congenital cutaneous nodules and a
      t(7;22)(p21;q11.2). The biologic behavior of the tumor diverged over time from a
      slowly growing tumor with multiple cutaneous nodules to a more aggressive
      neoplasm characterized by pulmonary metastases and a soft tissue mass showing
      additional cytogenetic alterations.

PMID- 9589086
TI  - Interferons in pediatric oncology: end of the beginning or beginning of the end?

PMID- 9589088
TI  - Primary non-Hodgkin lymphoma of the tongue in a child.

PMID- 9589087
TI  - Successful treatment of essential thrombocythemia with anagrelide in a child.

PMID- 9589089
TI  - Poorly differentiated squamous cell carcinoma of the parotid gland in a 13-year
      old girl.

PMID- 9589090
TI  - Tissue plasminogen activator and obstructed central venous catheters.

PMID- 9589091
TI  - [TIPSS: 10 years of clinical experience].
AB  - To demonstrate and document 10 years of clinical experience gathered by us with
      TIPSS and to discuss achievements, problems and outlook. MATERIAL AND METHODS:
      The analysis is based on the following parameters: portosystemic gradient;
      morphological delineation of the portal circulation; determination of the portal
      perfusion fraction (PPF) and the total liver perfusion (GLP); arterial flow
      changes; hepatic encephalopathy; incidence of restenotic shunt occlusion and
      recurrent variceal bleeding. RESULTS: Variceal filling was widely reduced by
      TIPSS, and significantly reduced portal liver perfusion as assessed
      morphologically and rheologically. However, there was an immediate onset of
      compensated liver perfusion by increased arterial inflow. Total liver perfusion
      did not change significantly. In TIPSS portal decompression was readily achieved,
      the portosystemic gradient dropping from an average of 24 mm Hg to 10.5 mm Hg. In
      our series we could not demonstrate an increased incidence of hepatic
      encephalopathy during the 30-day post-TIPSS period. Early mortality was 4% and
      early rebleeding rate 3%. The 12-month re-intervention rate based on an invasive
      portography follow-up protocol was 76%, and the 24-month re-intervention rate was
      90%. The definite occlusion rate was below 5%. Beyond a follow-up time span of 24
      months the necessity for re-intervention dropped significantly: less than one
      third of our patients required some sort of re-intervention. CONCLUSION: The
      concept of TIPSS represents an individually calibrated H-shunt. The significant
      reduction of post-TIPSS portal perfusion appears to be compensated by increased
      arterial inflow. This is reflected by an invasive flow measurement results and by
      the clinical results. Lethality of TIPSS is low mostly as a result of a refined
      technique, careful patient selection, follow-up care and meticulous shunt
      surveillance.

PMID- 9589092
TI  - [Low-field MR arthrography of the shoulder: early results using an open 0.2T MR
      system].
AB  - PURPOSE: To assess the practicability and image quality of doing MR arthrography
      of the shoulder using a 0.2T system. PATIENTS AND METHOD: 60 patients (24 with
      chronic instability, 36 with impingement syndrome) were examined in an open 0.2T
      MR apparatus (Magnetom Open, Siemens). After the intra-articular injections of 15
      20 ml of a 2 mmol Gd-DTPA solution, coronary STIR, T1-weighted, sagittal and
      axial T2*-weighted FLASH 2D sequences were performed. 21 patients subsequently
      underwent surgery. RESULTS: Image quality of the T1- and T2*-weighted FLASH 2D
      sequences was regarded as good or adequate and movement artifacts were minor or
      moderate. STIR sequences were statistically significantly worse in respect of
      image quality and movement artifacts (p < 0.001, p < 0.005). The sensitivity and
      specificity in the diagnosis of rotator cuff rupture as confirmed by surgery was
      100% (labrum lesions 100%, 93%). Agreement in the diagnosis of rupture of the
      supraspinatus and infraspinatus tendons was 0.93 and 0.65. CONCLUSION: MR
      arthrography of the shoulder using an open 0.2 T MR system provides adequate
      information concerning the intra articular structures of the joint. The
      disadvantage is the prolonged duration of the examination with the risk of poor
      image quality resulting from movement artifacts.

PMID- 9589093
TI  - [Magnetic resonance tomography in plasmacytoma: ranking of various sequences in
      diffuse and focal infiltration patterns].
AB  - PURPOSE: The aim of this study was to compare various pulse-sequences employing
      the spine array coil while considering the different infiltration patterns in
      multiple myeloma, in order to develop a fast and cost effective screening method.
      MATERIALS AND METHODS: In a prospective study, 50 patients with histologically
      proven multiple myeloma were examined with the following standardised sequences:
      T1-weighted SE, T2-weighted FSE, opposed phase GRE, FSE STIR, T1-weighted SE post
      gadopentate dimeglumine without and with fat saturation. The images were
      evaluated in a ROC analysis by three radiologists in consensus with a 5-grade
      scale separatively for diffuse and focal involvement. The gold standard was bone
      marrow histology in cases of diffuse infiltration and the combination of all
      sequences with the staging system according to Durie and Salmon. RESULTS: For
      focal bone marrow involvement the area under curve was greatest for FSE STIR
      sequences, in cases of diffuse infiltration the area under curve was superior for
      unenhanced T1-w SE-Sequenz images. The sensitivity can be increased by contrast
      material application and signal intensity measurements. A combined focal and
      diffuse infiltration and a "salt and pepper" pattern can be diagnosed with the
      combination of T1-w SE-Sequenz and FSE STIR sequences. CONCLUSION: With T1
      weighted SE-Sequenz sequences pre- and post-contrast and FSE STIR all
      therapeutical relevant infiltration patterns of plasmocytoma can be identified
      and bone marrow screening of the spine can be carried out with an acquisition
      time of 5.58 minutes.

PMID- 9589094
TI  - [Ultra-rapid T2-weighted MR imaging during suspended respiration for the
      examination of focal lesions of the liver: a comparison of TSE, HASTE and HASTE
      STIR sequences using a CP body array coil].
AB  - PURPOSE: A comparison of ultra rapid T2-weighted HASTE and HASTE-STIR sequences
      during suspended respiration for the detection of focal lesions of the liver.
      MATERIAL AND METHODS: Twenty-one patients (59 +/- 12 years) with a total of 33
      focal lesions (7 < or = 1 cm, 19 < or = 3 cm; 17 cystic liquid and 16 solid
      lesions) were examined with a 1.5 T MR apparatus. Sequences: T2 weighted HASTE
      (TEeff = 64 ms, 90 ms), HASTE-STIR (TEeff = 64 ms, 81 ms) TSE (TE = 132 ms) and
      T1-weighted FLASH 2D. RESULTS: The T2-weighted TSE and both HASTE sequences
      showed all the lesions. Two out of the 33 lesions were not demonstrated by the
      other sequences. Best image quality without movement artefacts and the best
      resolution of the lesions in the T2-weighted sequences, with the most favourable
      contrast/noise ratio (36.6 +/- 33.1) and signal/noise ratio (20.8 +/- 10.5)
      resulted from the HASTE 90, followed by the HASTE 64 sequence (27.5 +/- 24.2;
      24.6 +/- 9.1). Both these techniques were superior to the TSE sequence (23.9 +/-
      29.4; 13.9 +/- 7.4), which resulted in movement artifacts. With the HASTE-STIR
      sequences it was possible to show 31 and 32 of the 33 lesions respectively, with
      very good resolution but poor signal/noise ratio. CONCLUSION: HASTE sequences
      have the potential of improving the diagnosis of focal liver lesions.

PMID- 9589095
TI  - [RARE urography in pelvic tumors: diagnostic ranking and comparison with
      intravenous pyelography].
AB  - PURPOSE: To examine if RARE urography may replace conventional intravenous
      urography in patients with suspected urinary obstruction in pelvic tumours.
      MATERIALS AND METHODS: In a prospective trial on 120 patients with pelvic tumours
      scheduled for operation, biplanar RARE urography was performed and compared to
      conventional intravenous urography and ultrasound findings. RESULTS: In 30 out of
      120 patients an ureteric obstruction was diagnosed by ultrasound. Sensitivity of
      RARE urography for obstruction was 98% as compared to 60% in conventional
      intravenous urography. In 12 patients additional retrograde cystoureterography
      showed a sensitivity of 83%. Specificity of RARE urography and intravenous
      urography was 100%. In combination with axial MR tomography RARE urography
      yielded a more precise localisation of the site of obstruction and the underlying
      cause (98%) as compared to conventional urography (60%) and ultrasound (56%).
      CONCLUSION: By use of RARE urography urinary obstruction can be reliably
      demonstrated or ruled out. Combining RARE urography with tomographic MR imaging
      allows the precise depiction of the site of the obstruction and may demonstrate
      the underlying pathology.

PMID- 9589096
TI  - [Native and signal-enhanced power Doppler sonography for characterization of
      liver lesions].
AB  - PURPOSE: To evaluate the characterisation of liver lesions using power Doppler
      sonography before and after intravenous injection of the ultrasound contrast
      agent Levovist. MATERIALS AND METHODS: 39 patients with 41 liver lesions (10
      haemangiomas, 2 focal nodular hyperplasias (FNH), 2 focal fatty infiltrations, 1
      echinococcal lesion, 11 hepatocellular carcinomas, 14 metastases and one
      cholangiocarcinoma) were evaluated prospectively. Power Doppler images before and
      after intravenous injection of the ultrasound contrast agent Levovist were
      analysed by two radiologists and one gastroeterologist, who subjectively
      classified the distribution (peripheral, central, diffuse) and amount (none,
      minimal, moderate and strong) of flow pattern in each sonographic examination.
      Histological verification was obtained in all liver lesions, except in
      haemangiomas, where MR imaging and in one FNH where scintigraphy was regarded as
      sufficient proof. RESULTS: On the whole, power Doppler sonography after contrast
      injection was superior to unenhanced power Doppler-sonography in 20 liver lesions
      and equal in 7. After contrast injection, previously visible flow was enhanced in
      14 patients, in 6 lesions flow was detected, which was not seen before in the
      power mode. Moderate or strong flow signals were detected before contrast
      injection in 8/26, post contrast injection in 18/26 malignant tumours.
      Contrawise, 13/15 benign lesions did show any or only minimal flow signals before
      and 10/15 after contrast injection. CONCLUSION: Intratumoural flow signals favour
      a malignant tumour. The absence of flow signals is a frequent finding in benign
      lesions but does not rule out malignancy.

PMID- 9589097
TI  - [ACOnet (Austrian Academic Computer Network) as data carrier for teleradiologic
      consultations].
AB  - PURPOSE: To assess the feasibility of image transfer for teleradiologic
      consultations using the Austrian Academic Computer Network (ACOnet). The ACOnet
      corresponds between the main universities to a MAN (Metropolitan Area Network)
      with a transfer rate of 4 Mbps. Its use is free of charge for university
      institutions. MATERIALS AND METHODS: 1740 test image data sets and 620 image data
      sets for teleradiological consultations were exchanged without annotations
      between the Departments of Diagnostic Radiology of the universities of Innsbruck
      and Graz, using the ACOnet. RESULTS: Data transmission was reliable and fast with
      an average transfer capacity of 170.2 kBytes/s (94-341 kBytes/s). There were no
      major problems with image transfer during the test phase. CONCLUSION: Due to its
      high transfer capacity, the ACOnet is considered a reasonable alternative to the
      ISDN service.

PMID- 9589098
TI  - [Prevalence of abdominal aortic aneurysms: a sonographic screening study].
AB  - PURPOSE: To determine the prevalence of abdominal aortic aneurysms (AAA) in males
      above 60 years of age. METHODS: 1043 males of 60 years of age or older underwent
      sonographic examinations of the abdominal aorta. All of the candidates had
      volunteered for the examination, and special care was taken to avoid preselection
      of the candidates. Wherever possible, information was obtained on the following
      risk factors: cholesterol level, nicotine, diabetes, insulin and other
      medication, hypertonia and cardiac risk. RESULTS: An AAA was diagnosed in 2.59%
      of the cases, while ectasia of the abdominal aorta was detected in 11.89%. The
      mean diameter of the aneurysms was 39.1 mm. Significant correlations between the
      various risk factors and abnormalities of the abdominal aorta could be
      established in patients suffering from angina pectoris (p = 0.004) and from
      congestive heart failure (p = 0.014). CONCLUSIONS: AAA in males above 60 occurs
      in 2,590 out of 100,000 cases. The most noteworthy risk factors in the
      development of AAA are cardiovascular disorders.

PMID- 9589099
TI  - [TIPSS: technical and clinical results after 4 years].
AB  - PURPOSE: Retrospective analysis of the technical and clinical results after
      transjugular portosystemic stent shunt (TIPSS) procedure. METHOD: Between 1992
      and 1996 we tried to establish a TIPSS in 90 patients. The indications were:
      recurrent variceal haemorrhage (n = 74), refractory ascites (n = 12), hepatorenal
      syndrome (HRS) (n = 4). Due to advanced liver cirrhosis 16 patients suffered of
      severe renal dysfunction (HRS). 57 patients had ascites. RESULTS: TIPSS
      implantation was technically successful in 96.7% (1992-1994: 5.1%, 1995-1996:
      100%) of the patients. Complications occurred in 14.9% (1992-1994: 25.6%, 1995
      1996: 6.3%). TIPSS-associated mortality was 2.3% (1992-1994: 5.1%, 1995-1996:
      0%). 76.1% of the patients required reinterventions. 85.3% of reinterventions
      were necessary in the first year after TIPSS placement. The survival rate without
      reintervention was 28%, 21% and 9% for Child A, B, and C patients, respectively.
      Recurrent variceal haemorrhage occurred in 12.7%. De novo hepatic encephalopathy
      developed in 13.8%. Ascites improved in 79.2% and renal function in 75% of the
      patients. CONCLUSION: TIPSS is an effective method to treat recurrent variceal
      haemorrhage, refractory ascites and HRS. Complication and mortality rate depend
      on the investigator's experience and on the technique used.

PMID- 9589100
TI  - [Intra-arterial calcium stimulation for preoperative localization of insuloma].
AB  - PURPOSE: Objective is to evaluate the efficacy of the intraarterial calcium test
      in the preoperative localisation of insulinomas. MATERIAL AND METHOD: To
      stimulate the pathological release of insulin, calcium gluconate (0.015 meq
      Ca++/kg) was selectively injected into the arteries supplying the pancreas. Prior
      to calcium injection and 30, 60, 90 and 120 seconds later, 5 ml samples of blood
      were obtained from the right or from both right and left hepatic veins. Insulin
      levels were then determined by mean of immunoassays. A twofold increase in
      insulin level in the venous sample after 30 or 60 seconds localised the
      insulinoma to the region of the pancreas supplied by the selectively injected
      artery. Results of the calcium test were prospectively analysed in 6 patients and
      compared with operative findings. RESULTS: All 6 patients had a surgically proved
      solitary and benign insulinoma. Calcium stimulation with venous sampling provided
      true-positive localisation of insulinomas in all patients without suspicion of
      liver metastasis. All 6 patients currently have normal insulin levels after a
      mean period of 16 months (range 4-24 months) with no evidence of hypoglycaemia on
      fasting. CONCLUSION: Intraarterial stimulation with calcium and hepatic vein
      samplings for insulin gradients is a very sensitive minimally invasive functional
      method and may replace transhepatic portal venous samplings for the preoperative
      detection of insulinomas.

PMID- 9589101
TI  - [New method of MR-guided mammary biopsy].
AB  - PURPOSE: With a recently installed new open MR tomograph (Signa SP, General
      Electric MS) it is possible for the first time to examine patients with obscure
      lesions of the mamma by MR imaging in a sitting position, similar to mammography.
      METHOD: The newly developed positioning device with integrated surface coil
      permits in combination with the vertical gap in the new magnet and imaging of the
      mamma with a "real time" sequence a biopsy procedure within a short time and in a
      manner that is acceptable for the patient. By means of an integrated interactive
      scan plane guiding system ("flash point tracking system") and special MR
      compatible needles and wires tissue samples can be taken, or marking by a wire
      can be carried out within a short time. RESULTS: Phantom experiments and first in
      vivo experience (10 patients) show that by means of the new mamma fixation and
      biopsy device a MRI of one breast in a sitting position for detecting an
      enhancing lesion and a MR-guided biopsy of this lesion is possible. The whole
      procedure takes about 25-35 minutes, comparable to the conventional stereotactic
      method. CONCLUSION: Direct patient access and the interactive guided biopsy allow
      in future both new diagnostic information (histological results after biopsy or
      after wire-guided open biopsy of a lesion only visible in MR) and the development
      of minimal invasive therapeutic procedures, e.g. MR-guided and -controlled
      interstitial thermotherapy.

PMID- 9589102
TI  - [Emergency decompression of a mechanical colonic ileus before elective surgery:
      first clinical results of fluoroscopic stent placement].
AB  - PURPOSE: Evaluation of fluoroscopic stent placement as an emergency therapeutical
      approach for treatment of acute large bowel obstruction due to colorectal
      neoplasm. METHODS AND MATERIAL: From January to December 1996 in 11 patients
      suffering from colorectal stenosis due to known or supposed malignancy the
      indication for the fluoroscopic placement of self-expanding metal stents was
      established. All patients showed clinical and radiological signs of an acute
      mechanical large bowel obstruction. Elective single-stage surgery was planned if
      the decompression had been carried out successfully. RESULTS: Stent placement was
      successful in 8 cases. Functional success in respect of resolving the acute large
      bowel obstruction was seen in 7 out of 11 patients. Elective surgery was possible
      in all 7 cases creating a primary end-to-end anastomosis without major
      complications during the perioperative period. CONCLUSION: Fluoroscopic placement
      of self-expanding metal stents in malignant colorectal stenosis is a promising
      method to avoid emergency surgery.

PMID- 9589104
TI  - [Diagnosis of an occipital condyle fracture using MRI].

PMID- 9589103
TI  - [MR-micturating cystourethrography using radical k-space sampling].
AB  - PURPOSE: To investigate the feasibility of micturating cystourethrography (MCU)
      by means of real-time MR imaging with radial k-space sampling. METHODS: The MR
      MCU was performed in 7 adult male patients subsequent to a gadolinium(Gd)-DTPA
      enhanced excretory MR-urography. The Gd-enhancement of the urethra was visualized
      by MR-fluoroscopy using a T1-weighted gradient-echo-sequence with radial k-space
      sampling and a slice thickness of 10 mm. RESULTS: The proposed technique allowed
      in all 7 patients a dynamic realtime imaging of the Gd-flow inside the urethra
      during micturition. The normal anatomy of the entire course of the urethra was
      demonstrated in each patient, while simultaneously the relation to the prostate
      and pelvic floor became visible. Furthermore, the urinary bladder could be
      assessed by interactive repositioning of the slice orientation in any preferred
      direction. The ureters could also be visualized due to the persisting Gd
      enhancement of the upper urinary tract after the preceding MR-urography.
      CONCLUSIONS: MR-MCU using Gd-DTPA and radial k-space data acquisition is a novel
      imaging modality for a real-time visualization of the urethra during micturition
      without radiation exposure. This method also allows the assessment of the
      bladder, the pelvic floor, and the Gd-filled upper urinary tract which suggests a
      potential for the diagnosis of vesicoureteral reflux and urinary incontinence.

PMID- 9589105
TI  - [Acute Budd-Chiari syndrome--successful treatment based on TIPSS].

PMID- 9589106
TI  - [Erdheim-Chester lipogranulomatosis with involvement of the breast].

PMID- 9589108
TI  - [Accumulation of radioactivity in the lung after 111In-octreotide scintigraphy].

PMID- 9589107
TI  - [Cerebral MRI in pre-eclampsia and eclampsia].

PMID- 9589109
TI  - [Ileocecal tuberculosis as a cause of lower gastrointestinal hemorrhage in lupus
      erythematosus].

PMID- 9589110
TI  - [Pigmented villonodular synovitis of the hip].

PMID- 9589111
TI  - Dog bite prevention campaign: nipping a problem in the bud.

PMID- 9589112
TI  - Update on vaccine-associated sarcoma.

PMID- 9589113
TI  - Cognitive dysfunction in dogs, cats an Alzheimer's-like disease.

PMID- 9589114
TI  - New product reduces salmonellae in chickens.

PMID- 9589115
TI  - Reminder of beef quality assurance program.

PMID- 9589116
TI  - Concerns regarding treatment of veterinarians with disabilities.

PMID- 9589117
TI  - Homeopathy article induces debate.

PMID- 9589118
TI  - Homeopathy article induces debate.

PMID- 9589119
TI  - Comfort as the primary goal in veterinary medical practice.

PMID- 9589120
TI  - What is your diagnosis? Pneumopericardium and pulmonary alveolar disease
      (consistent with pulmonary contusions).

PMID- 9589121
TI  - Surgical repair of bilateral comminuted articular ulnar fractures in a seven
      month-old horse.

PMID- 9589122
TI  - Animal behavior case of the month. Aggression of a cat toward its owner when
      cleaning the cat's litter box.

PMID- 9589123
TI  - Survey of occupational hazards in companion animal practices.

PMID- 9589124
TI  - Reducing your liability potential.

PMID- 9589125
TI  - Ionized and total magnesium concentrations in blood from dogs with naturally
      acquired parvoviral enteritis.
AB  - OBJECTIVE: To determine whether pretreatment total and ionized blood magnesium
      concentrations were associated with outcome for dogs with parvoviral enteritis
      and whether ionized magnesium concentration was related to total magnesium
      concentration or other laboratory values. DESIGN: Prospective cohort study.
      ANIMALS: 61 healthy dogs and 72 dogs with parvoviral enteritis. PROCEDURE: Total,
      ionized, and pH-normalized ionized magnesium concentrations, ionized and pH
      normalized ionized calcium concentrations, pH, sodium and potassium
      concentrations, and Hct were measured prior to treatment. chi 2 Analyses were
      used to test for associations between outcome and age and between outcome and
      treatment with antiendotoxin antibody. Pearson's correlation coefficients were
      calculated to determine whether ionized magnesium concentration was linearly
      associated with other laboratory values. RESULTS: Total and ionized magnesium
      concentrations were not significantly different between healthy dogs and dogs
      with parvoviral enteritis or between dogs surviving and those not surviving
      parvoviral enteritis. The only laboratory value strongly correlated with ionized
      magnesium concentration was pH-normalized ionized magnesium concentration. Of the
      factors tested, none were significantly associated with outcome, except that dogs
      16 weeks old or less treated with antiendotoxin antibody were significantly more
      likely to die than were dogs 16 weeks old or less that were not treated with
      antiendotoxin antibody. CLINICAL IMPLICATIONS: Total and ionized blood magnesium
      concentrations cannot be used to consistently predict outcome for dogs with
      parvoviral enteritis. Antiendotoxin antibody should be used with caution in dogs
      16 weeks old or less.

PMID- 9589126
TI  - Neoplastic diseases in ferrets: 574 cases (1968-1997).
AB  - OBJECTIVE: To determine incidence of neoplastic disease in ferrets. DESIGN:
      Retrospective study. ANIMALS: 574 ferrets with neoplastic disease. PROCEDURE:
      Medical records from the Veterinary Medical Data Base at Purdue University from
      1968 to May 1997 were reviewed to identify ferrets with neoplastic disease. Data
      on tumor type, organ or system affected, sex, age, geographic location of
      affected ferrets, participating institution, and year of diagnosis were
      retrieved. RESULTS: 639 tumors of various types were diagnosed in 574 of 4,774
      (12%) ferrets in the database. Sixty-one ferrets had multiple tumor types.
      Primary tumors were found in every system; endocrine (254; 39.7%), hemolymphatic
      (97; 15.2%), integumentary (83; 12.9%), and digestive (54; 8.4%) systems were
      most commonly affected. The most common tumor types were pancreatic islet cell
      (139; 21.7%) and adrenocortical cell (107; 16.7%) tumors and lymphoma (76;
      11.9%). Most (94.2%) pancreatic islet cell tumors were functional. Age of
      affected ferrets ranged from less than 1 month to more than 15 years old. Tumor
      incidence was highest in ferrets between 4 and 7 years old. A sex predilection
      was not found, although tumors were found more commonly in spayed females and
      castrated males than in sexually intact females and males, respectively. Number
      of tumors diagnosed increased as the number of ferrets examined increased.
      Neoplastic disease accounted for an increasingly greater percentage of diseases
      diagnosed in ferrets during the study period. CLINICAL IMPLICATIONS: Ferrets have
      an incidence and spectrum of neoplastic disease similar to other mammalian
      species.

PMID- 9589127
TI  - Effect of ranitidine on intragastric pH in clinically normal neonatal foals.
AB  - OBJECTIVE: To determine intragastric pH in newborn foals and to examine the
      effect of i.v. or oral administration of an H2-receptor antagonist on
      intragastric pH. DESIGN: Prospective controlled study. ANIMALS: 6 healthy mixed
      breed neonatal foals. PROCEDURE: Intragastric pH was measured, using an antimony
      electrode. Foals were monitored on days 2, 4, and 6 after birth, and each
      received 3 treatments. The pH was recorded for 4 hours before treatment and for
      10 hours after ranitidine administration (2 mg/kg [0.91 mg/lb] of body weight,
      i.v.; 6.6 mg/kg [3 mg/lb], PO) or 20 hours after corn syrup administration. Mean
      and median pH and percentage of time pH was > or = 4 were calculated. RESULTS:
      Mean intragastric pH significantly increased for 5 hours after i.v.
      administration of ranitidine, compared with baseline data. Percentage of time
      intragastric pH was > or = 4 increased significantly for 4 hours after ranitidine
      administration, and median pH increased significantly for hours 2 to 4 after
      administration. Oral administration of ranitidine significantly increased mean
      and median pH for hours 2 to 8 after administration and percentage of time pH was
      > or = 4 for hours 2 to 7 after administration. CLINICAL IMPLICATIONS: Neonatal
      foals have highly acidic gastric fluid. Intravenous or oral administration of
      ranitidine significantly increased intragastric pH for 4 and 8 hours,
      respectively. Suckling affected intragastric pH and underscored the need for
      frequent feeding of neonatal foals.

PMID- 9589128
TI  - Lateral approach for arthrocentesis of the distal interphalangeal joint in
      horses.
AB  - OBJECTIVE: To determine anatomic landmarks for a lateral approach for
      arthrocentesis of the proximopalmarolateral aspect of the distal interphalangeal
      (DIP) joint in horses and the likelihood of entering synovial structures other
      than the DIP joint through this approach. DESIGN: Prospective study. SAMPLE
      POPULATION: Paired forelimbs of 8 cadavers and 12 horses. PROCEDURE: Anatomic
      preparations were used to determine anatomic landmarks. Positive-contrast
      arthrography was used to determine which structures were entered. RESULTS:
      Landmarks for the lateral approach included a depression in the proximal border
      of the lateral ungular cartilage and the palmar border of the middle phalanx. Use
      of the lateral approach for arthrography resulted in deposition of contrast
      material exclusively in the DIP joint in only 13 of 20 limbs, whereas use of the
      dorsal approach resulted in deposition of contrast material exclusively in the
      DIP joint in 20 of 20 limbs. CLINICAL IMPLICATIONS: The lateral approach is an
      alternative to the conventional dorsal approach to the DIP joint in horses,
      however, inadvertent entry into adjacent synovial structures is a possible
      complication. The lateral approach provides an additional portal for through-and
      through lavage and arthroscopic access to the palmar aspect of the DIP joint.

PMID- 9589129
TI  - Regression of subcutaneous lymphoma following removal of an ovarian
      granulosatheca cell tumor in a horse.
AB  - A 9-year-old Arabian mare was admitted for evaluation of multiple subcutaneous
      nodules and infertility. Fine-needle aspiration of one of the subcutaneous
      nodules resulted in a cytologic diagnosis of histiolymphocytic lymphoma.
      Palpation per rectum and transrectal ultrasonography revealed a mass associated
      with the left ovary. Excision of the ovarian tumor was performed, and a
      histopathologic diagnosis of granulosa-theca cell tumor was made. After removal
      of the granulosa-theca cell tumor, subcutaneous nodules regressed. The referring
      veterinarian reported that the nodules had also disappeared and then recurred
      after administration of a synthetic progestin. To further characterize the
      lymphoma and investigate this possible hormonal relationship, immunophenotyping
      and estrogen and progesterone receptor assays were performed. The subcutaneous
      lymphoma was classified as a T-cell rich B-cell lymphoma, results of estrogen
      receptor assays were negative, and results of progesterone receptor assays were
      positive. Clinical observations of subcutaneous lymphoma in horses indicate that
      the waxing and waning nature of these tumors may be associated with the estrous
      cycle, pregnancy, foaling, and lactation. Clinical observations and
      identification of progesterone receptors suggest that a relationship between
      serum steroid hormone concentrations, such as estrogen and progesterone, and
      subcutaneous lymphoma may exists.

PMID- 9589130
TI  - Use of clinical parameters for differentiation of gram-positive and gram-negative
      mastitis in dairy cows vaccinated against lipopolysaccharide core antigens.
AB  - OBJECTIVE: To determine whether clinical parameters could be used to
      differentiate clinical mastitis (CM) caused by gram-positive bacteria from CM
      caused by gram-negative bacteria in dairy cows vaccinated against
      lipopolysaccharide core antigens. DESIGN: Case series. ANIMALS: 143 episodes of
      CM in 86 dairy cows in a single herd. PROCEDURE: Cows were examined at onset of
      CM, and 24 clinical parameters including rectal temperature, heart rate, rumen
      contraction rate, degree of dehydration, various udder and milk characteristics,
      lactation number, stage of lactation, and season of year were recorded. Milk
      production and milk constituent concentrations before onset of CM were obtained
      from Dairy Herd Improvement Association records. Values for cows with gram
      negative CM were compared with values for cows with gram-positive CM. Logistic
      regression was used to identify important predictors of gram-negative CM.
      RESULTS: 64 (45%) CM episodes were caused by gram-negative bacteria and 79 (55%)
      were caused by gram-positive bacteria. Rumen contraction rate was significantly
      lower and milk protein percentage before onset of CM was significantly higher in
      cows with gram-negative, rather than gram-positive, CM. Logistic regression
      indicated that CM was more likely to have been caused by gram-negative bacteria
      if it developed during the summer, milk was watery, or rumen contraction rate was
      low. Sensitivity and specificity of the final regression model were 0.58 and
      0.80, respectively. Predictive value of a positive result was 0.74 when
      proportion of CM episodes caused by gram-negative bacteria was assumed to be 50%.
      CLINICAL IMPLICATIONS: Results suggest that clinical observations do not allow
      accurate prediction of CM pathogens and should not be the sole criteria for
      deciding whether cows with CM are treated with antibiotics.

PMID- 9589131
TI  - Implantation of a reinforced polytetrafluoroethylene vascular graft for treatment
      of obstructions of the teat and mammary gland cisternae in cattle.
AB  - OBJECTIVE: To evaluate use of an artificial vascular graft as treatment for
      obstructions of the teat and mammary gland cisternae in lactating cattle. DESIGN:
      Prospective clinical study. ANIMALS: 14 lactating dairy cows. PROCEDURE: After
      physical examination that included palpation, ultrasonography, evaluation of milk
      flow, and California mastitis test, each cow underwent surgical excision of
      obstructive tissue and implantation of a reinforced polytetrafluoroethylene
      vascular graft. Milk drained passively for 10 to 14 days after surgery. Follow-up
      evaluation was performed by telephone questionnaire of owners 1, 6, and 12 months
      after surgery regarding somatic cell count, time needed to milk affected quarter,
      compared with that of the contralateral quarter, and frequency of mastitis. After
      the subsequent nonlactation period and calving, milk flow was tested, using a
      quarter milking machine, and ultrasonographic examination of the affected teat
      was performed. RESULTS: Milk could be obtained from affected quarters from all
      cows 14 days after surgery, from 13 (93%) cows 1 month after surgery, from 10
      (71%) cows 6 months after surgery, and from 3 (21%) cows 12 months after surgery,
      but milk flow in these 3 cows was considerably reduced. This technique failed
      because of collapse of the implant (4 cows), chronic mastitis (1), migration of
      the implant (4), and ingrowth of obstructive tissue between the distal aspect of
      the implant and the ridges of mucous membrane that radiate from the internal
      orifice of the streak canal (4), or a combination of these. CLINICAL
      IMPLICATIONS: Implantation of this vascular graft is a useful technique to
      restore teat patency for 6 months. A longer period of passive drainage of milk
      appears necessary for sufficient ingrowth of the graft. Lesions that extend to
      the distal most aspect of the teat cistern have a poor prognosis, because this
      area cannot be sufficiently overlapped by the graft.

PMID- 9589132
TI  - Surgical correction of an acquired vaginal stricture in a llama, using a carbon
      dioxide laser.
AB  - An acquired vaginal stricture in a llama secondary to trauma from uterine torsion
      during gestation was repaired, using a carbon-dioxide laser. The procedure was
      accomplished by use of epidural anesthesia with the llama in a standing position.
      Repeated dilation of the vagina was required after surgery; however, the llama
      subsequently mated and conceived, and a male cria was delivered by cesarean
      section at the end of a full-term gestation.

PMID- 9589133
TI  - Gastrointestinal ulceration and pulmonary aspergillosis in a llama treated for
      parelaphostrongylosis.
AB  - A 9-year-old llama examined because of hind limb paresis was found to have
      parelaphostrongylosis. Despite treatment with ivermectin, fenbendazole,
      cimetidine, and ceftiofur, the llama developed gastrointestinal ulceration and
      pulmonary aspergillosis and was euthanatized. Parelaphostrongylus tenuis is a
      parasite of white-tailed deer, but ruminants can serve as aberrant or dead-end
      hosts after accidentally ingesting snails or slugs carrying third-stage larvae of
      the parasite. Gastrointestinal ulceration and pulmonary aspergillosis can develop
      secondarily in llamas with chronic disease. Treatment of gastrointestinal
      ulceration in llamas is difficult, because efficacy of commonly used antiulcer
      drugs in llamas has not been established.

PMID- 9589134
TI  - Concurrent abomasal displacement and perforating ulceration in cattle: 21 cases
      (1985-1996).
AB  - OBJECTIVE: To evaluate the association of physical examination and
      clinicopathologic findings with surgical findings in cattle with concurrent
      abomasal displacement and perforating ulceration, to determine short- and long
      term survival rates in these cattle, and to determine whether degree of
      peritonitis (focal vs diffuse) influences survival rates. DESIGN: Retrospective
      study. ANIMALS: 21 cattle with concurrent abomasal displacement and perforating
      ulceration and 42 cattle with uncomplicated abomasal displacement. PROCEDURE:
      Information on signalment, stage of lactation, physical examination findings,
      clinicopathologic data, surgical diagnosis, procedure(s) performed, and necropsy
      findings were retrieved from medical records of all cattle included in this
      study. Differences between physical examination findings of cattle with
      concurrent disease and those of cattle with uncomplicated displacements were
      evaluated, as were differences between survival rates in cattle with focal versus
      diffuse peritonitis. RESULTS: Cattle with concurrent disease had a greater
      probability of having pneumoperitoneum and signs of abdominal pain identified on
      physical examination than did cattle with uncomplicated diseases. There was no
      relationship between clinicopathologic data and survival time. Short-term
      survival rate was 38%, and degree of peritonitis significantly influenced
      survival time in cattle with concurrent abomasal displacement and perforating
      ulceration. Long-term survival rate in these cattle was 14%. CLINICAL
      IMPLICATIONS: Cattle with concurrent displaced abomasum and perforating
      ulceration have a poor chance for survival. In addition to detection of displaced
      abomasum, physical examination findings that can help lead to a presurgical
      diagnosis of this syndrome are pneumoperitoneum and signs of abdominal pain.

PMID- 9589135
TI  - Comparative aspects of proliferative enteritis.

PMID- 9589136
TI  - Modern management of miscarriage: is there a place for non-surgical treatment?

PMID- 9589137
TI  - Predicting pulmonary hypoplasia: assessment of lung volume or lung function or
      both?

PMID- 9589138
TI  - Doppler waveforms from the pulmonary arterial system in normal fetuses and those
      with pulmonary hypoplasia.
AB  - Color, pulsed and power Doppler were used to image the fetal pulmonary
      vasculature in 150 normal pregnancies and ten pregnancies in which the fetus had
      bilateral multicystic dysplastic kidney disease (MCDK) and associated pulmonary
      hypoplasia. The normal fetuses had a high resistance pattern in the main
      pulmonary artery vasculature. There were no significant changes in the resistance
      of the main pulmonary artery, right pulmonary artery and left pulmonary artery,
      with increasing gestational age. In the peripheral pulmonary arteries the
      resistance was less with an increase in diastolic flow, with advancing gestation.
      All fetuses with MCDK died. This group did not have significantly different
      Doppler waveforms in the main pulmonary arteries, but Doppler signals from the
      peripheral pulmonary arteries showed a high resistance pattern quite different
      from that of normal fetuses. Doppler measurements of the peripheral pulmonary
      artery may give additional information useful in diagnosing pulmonary hypoplasia.

PMID- 9589139
TI  - Doppler echocardiography of the main stems of the pulmonary arteries in the
      normal human fetus.
AB  - The objective of this study was to describe the normal blood flow velocity
      waveforms in the main branches of the right and left pulmonary arteries in the
      human fetus and to establish reference ranges for different Doppler parameters
      during the second half of pregnancy. Cross-sectional data were collected from 86
      healthy human singleton fetuses between 18 and 38 weeks of gestation. With
      advancing gestation a significant increase (p < 0.001) in the peak systolic
      velocity, time averaged velocity and time velocity integral was observed. The
      pulsatility index decreased significantly (p < 0.05) in the same period,
      suggesting a decrease in the pulmonary arterial vascular resistance. The
      acceleration time (AT) and the ratio of AT to ejection time (AT/ET), described in
      postnatal cardiology as having an inverse correlation with mean arterial
      pressure, increased significantly (p < 0.001). This is possibly the result of
      decreased pulmonary arterial pressure. The data show that Doppler examination of
      blood flow in the main stem of both the right and the left pulmonary arteries of
      the fetus is feasible, and increases insight into the lung perfusion of the human
      fetus. The observed changes throughout gestation are in accordance with animal
      experiments showing an increase in perfusion as well as a decrease in the
      vascular resistance and pressure.

PMID- 9589140
TI  - In utero ultrasonographic measurements of fetal aortic and pulmonary artery
      diameters during the first half of gestation.
AB  - The study was conducted to construct a normal range for the diameters of the
      aortic root and pulmonary artery during the first half of gestation. With the use
      of transvaginal and transabdominal high-resolution ultrasound techniques, a
      prospective, cross-sectional study was performed on 139 normal singleton
      pregnancies at between 14 and 26 weeks. Great vessel diameters were measured by
      transvaginal ultrasonography until 17 weeks, and by transabdominal ultrasound
      between 18 and 26 weeks' gestation. The results showed that the aortic diameter
      (AD) as a function of gestational age (GA) was expressed by the regression
      equation AD = -16.0331 + 2.2563 x GA, and the pulmonary artery diameter (PD) by
      PD = -14.7637 + 2.4026 x GA; AD and PD are expressed in millimeters and GA in
      weeks. The correlation r2 = 0.94 was found to be highly statistically significant
      (p < 0.0001) for both great vessels. The normal mean of aortic and pulmonary
      artery diameter per week and the 95% prediction limits were also defined. During
      the study period we evaluated two cases with arterial diameters outside the 95%
      confidence limits; one had aortic coarctation and the other tetralogy of Fallot.
      The normative data established by us may be helpful in the prenatal diagnosis of
      congenital heart defects that include, among their manifestations, discordant
      diameters of the great vessels.

PMID- 9589141
TI  - Prenatal diagnosis of ductus venosus agenesis: a report of two cases and review
      of the literature.
AB  - Anomalies of venous return due to absence of the ductus venosus have been
      described in the literature. This is a report of the prenatal diagnosis of two
      cases of isolated ductus venosus agenesis occurring at 20 and 37 weeks'
      gestation, confirmed postnatally by color-coded Doppler sonography. In both cases
      the hepatic veins assumed the function of the ductus venosus without compromising
      fetal hemodynamics or causing hydrops. In the first case, a healthy female infant
      was delivered at term. In the second case, a 46,XY,dup(8) (q21.1q22)[35]/47,idem,
      + r(8)[15] karyotype was diagnosed by amniocentesis. The male newborn showed
      facial anomalies, a bell-shaped thorax and increased intermamillary distance.
      There was muscular hypotonia, delayed psychomotor development and an inspiratory
      stridor leading to obstructive nocturnal dyspnea. On the basis of our
      observations in these two cases and previous reports from animal studies, we
      conclude that absence of the ductus venosus may be compatible with normal fetal
      development without relevant disturbance of circulation and oxygenation.

PMID- 9589142
TI  - Ductus venosus agenesis prevents transmission of central venous pulsations to the
      umbilical vein in fetal sheep.
AB  - Velocity pulsations in the umbilical vein are widely used as a marker for
      congestive heart failure in the fetus. It has been suggested that the atrial
      pressure waves are transmitted to the umbilical vein mainly through the ductus
      venosus. In a case of ductus venosus agenesis in a fetal sheep of 110 days'
      gestation, we recorded pressures in the inferior vena cava and umbilical vein
      simultaneously with Doppler velocimetry in the medial hepatic vein and umbilical
      vein, under general anesthesia. During fetal respiratory acidosis (pH 7.01) and
      varying degrees of umbilical clamping, we did not observe the typical pulsations
      in the umbilical vein (deflections of the maximum velocity during atrial
      contraction) in spite of varying degrees of reversed flow in the hepatic vein (5
      16%). The systolic-diastolic pressure amplitude in the inferior vena cava was 5.5
      6.4 mmHg, sometimes reaching 9.19-11.03 mmHg. Varying degrees of reversed
      portocaval pressure gradient during atrial contraction (1.40-9.51 mmHg), periods
      of reversed portocaval pressure gradient throughout the entire cardiac cycle,
      tachycardia (240 beats/min) or bradycardia (99 beats/min) also did not produce
      the type of pulsation in the umbilical vein that reflects augmented atrial
      contractions. The results support the hypothesis that the ductus venosus is
      essential for the transmission of atrial pressure waves to the umbilical vein.

PMID- 9589143
TI  - Maternal middle cerebral artery velocity changes in HELLP syndrome versus pre
      eclampsia.
AB  - Our objective was to determine whether there is a difference in middle cerebral
      artery blood flow velocity in patients with the syndrome of hemolysis, elevated
      liver enzymes and low platelet counts (HELLP syndrome) compared to a matched
      controlled group of patients with pre-eclampsia and without HELLP syndrome. Six
      pre-eclamptic patients with HELLP syndrome and 12 pre-eclamptic women without
      HELLP syndrome had maternal middle cerebral artery blood flow velocity assessed
      antepartum and at 24 and 48 h postpartum. We compared the effect of the
      development of HELLP syndrome on middle cerebral artery blood flow velocity
      changes using non-parametric tests. Patients with HELLP syndrome showed no
      significant differences in diastolic, systolic, mean middle cerebral artery blood
      flow velocity or pulsatility index in either the antepartum or 24-h and 48-h
      postpartum phases when compared to non-HELLP pre-eclamptic patients. Our data
      suggest that there is no difference in the blood flow velocity waveform of the
      maternal middle cerebral artery between patients with pre-eclampsia and those
      with HELLP syndrome.

PMID- 9589144
TI  - Pulsatility index in the fetal anterior tibial artery during the second half of
      normal pregnancy.
AB  - The objective of this prospective study was to establish reference values for the
      pulsatility index in the fetal anterior tibial artery during the second half of
      pregnancy. Pulsed Doppler waveform analysis of 203 fetuses at 23-42 weeks of
      pregnancy was performed, each fetus being examined just once. There were neither
      fetal nor maternal complications detectable at the time of the examination. In
      the first 14 fetuses from which recordings were taken, Doppler examination was
      performed on both fetal legs in order to evaluate systematic differences between
      the right and left legs. Intraobserver variability was analyzed by repetition of
      the measurements by the same examiner in the first 130 cases. There was no
      difference between right and left tibial circulation. The repeatability
      coefficient, defined as the 95% range for the difference in two repeat
      measurements, was 1.08. The pulsatility index of the anterior tibial artery (50th
      centile) increased slightly from 3.29 at 23 weeks of pregnancy to 4.09 at 42
      weeks. The 5th and 95th centiles were calculated, as was the 95% confidence
      interval of the 5th and 95th centiles. Examination of the fetal peripheral
      circulation during the second half of pregnancy is possible with a high degree of
      precision. Whether there are changes in peripheral arterial circulation in
      compromised fetuses remains to be evaluated.

PMID- 9589145
TI  - Sonographic evaluation of intervillous flow in early pregnancy: use of echo
      enhancement agents.
AB  - The uteroplacental circulation of the cynomolgus monkey was examined in early
      pregnancy using a high-resolution ultrasound scanner. Intravenous injection of an
      echo-contrast agent, Albunex (sonicated albumin), was used to enhance the color
      Doppler images obtained. The flow of blood into and out of the intervillous
      compartment was readily assessed and quantified using pulsed and color Doppler.
      Flow within the intracotyledonary space was pulsatile and indicative of a low
      resistance system. Flow within the decidual veins was non-pulsatile. The use of
      echo-contrast agents may assist in the determination of intervillous flow in
      human pregnancy at a correspondingly early stage.

PMID- 9589146
TI  - Anomalous fetal venous return associated with major chromosomopathies in the late
      first trimester of pregnancy.
AB  - We report three cases of increased nuchal translucency at 12-13 weeks of
      gestation in three fetuses with trisomies 13, 18 and 21. All three fetuses were
      associated with anomalous venous return evaluated by Doppler ultrasonography.
      Complete pathological examination was performed following termination in each
      case. We suggest that alterations in the venous compartment can be an early sign
      of poor outcome and should prompt a detailed search for cardiac defects early in
      gestation.

PMID- 9589147
TI  - Prenatal sonographic characteristics and Doppler blood flow study in a case of a
      large fetal mediastinal teratoma.
AB  - Although fetal mediastinal teratomas may result in respiratory distress in the
      neonatal period and lead to perinatal mortality, they are rarely diagnosed
      prenatally. Furthermore, their impact on fetal hemodynamics has never been
      described. We report a case of a large fetal mediastinal teratoma prenatally
      visualized at 38 weeks' gestation by both two- and three- dimensional ultrasound.
      We also describe the associated changes in the Doppler flow velocimetry, namely,
      a decrease in cardiac output, prolonged acceleration time in the pulmonary artery
      and an increase in the umbilical artery S/D ratio. The baby was well at the 5
      month follow-up after an operation in the neonatal period. From our case, we
      believe that accurate prenatal diagnosis and assessment by two- and three
      dimensional ultrasound as well as Doppler flow velocimetry may contribute to a
      better perinatal outcome.

PMID- 9589148
TI  - Intra-abdominal sacrococcygeal mature teratoma or fetus in fetu in a third
      trimester fetus.
AB  - This case report describes a fetus with a large intra-abdominal, complex,
      vascular mass, displacing the normal intra-abdominal organs due to its large
      size. Extension to the presacral area was also identified, facilitating the
      diagnosis of a sacrococcygeal teratoma. Because of its highly mature nature, this
      was considered a fetus in fetu which was totally intra-abdominal.

PMID- 9589149
TI  - Recurrent bilateral theca lutein cysts in association with normal pregnancy.
AB  - We describe a case of a 28-year-old Saudi patient, gravida 6, para 5, at 14
      weeks' gestation, who had recurrent bilateral theca lutein cysts during her last
      three pregnancies. The cysts were treated surgically during her fourth pregnancy
      because of acute abdomen at 20 weeks' gestation. Ovarian biopsy confirmed the
      diagnosis of theca lutein cysts and her pregnancy continued until term. In the
      last two pregnancies, the theca lutein cysts were managed conservatively by
      serial ultrasound examination and they resolved spontaneously. There was no
      history of molar pregnancy or use of ovulation-inducing drugs. The possibility
      that there was increased sensitivity of the ovarian tissue to human chorionic
      gonadotropin is discussed.

PMID- 9589150
TI  - Placental polyp: power Doppler imaging and conservative resection.

PMID- 9589151
TI  - Small bowel atresia: antenatal intestinal vascular accident or parvovirus B19
      infection?

PMID- 9589152
TI  - Making medical choices.

PMID- 9589154
TI  - Benign conditions.

PMID- 9589153
TI  - Allergic rhinitis.

PMID- 9589155
TI  - Working out in water.

PMID- 9589156
TI  - Low-dose estrogen for bone loss.

PMID- 9589157
TI  - The wine scorecard.

PMID- 9589158
TI  - Occasionally, I feel rather strong "flutterings" of pulse low in my neck. It can
      occur several times within a week or two and then not again for a month or so. I
      was given a monitor to wear, and it showed nothing that my doctor considered
      important. However, at 57 this is new for me. Should I still be concerned?

PMID- 9589159
TI  - A health-conscious friend told me that carbonated drinks leach calcium from
      bones. Is this true? I'm wondering whether taking my calcium pills with seltzer
      counteracts their good effects.

PMID- 9589160
TI  - Responses of cultured rat trigeminal ganglion neurons to bitter tastants.
AB  - The initial steps in taste and olfaction result from the activation by chemical
      stimuli of taste receptor cells (TRCs) and olfactory receptor neurons (ORNs). In
      parallel with these two pathways is the chemosensitive trigeminal pathway whose
      neurons terminate in the oral and nasal cavities and which are activated by many
      of the same chemical stimuli that activate TRCs and ORNs. In a recent single unit
      study we investigated the responses of rat chorda tympani and glossopharnygeal
      neurons to a variety of bitter-tasting alkaloids, including nicotine, yohimbine,
      quinine, strychnine and caffeine, as well as capsaicin, the pungent ingredient in
      hot pepper. Here we apply many of these same compounds to cultured rat trigeminal
      ganglion (TG) neurons and measure changes in intracellular calcium [Ca2+]i to
      determine whether TG neurons will respond to these same compounds. Of the 89
      neurons tested, 34% responded to 1 mM nicotine, 7% to 1 mM caffeine, 5% to 1 mM
      denatonium benzoate, 22% to 1 mM quinine hydrochloride, 18% to 1 mM strychnine
      and 55% to 1 microM capsaicin. These data suggest that neurons from the TG
      respond to the same bitter-tasting chemical stimuli as do TRCs and are likely to
      contribute information sent to the higher CNS regarding the perception of
      bitter/irritating chemical stimuli.

PMID- 9589161
TI  - Effects of context on judgements of odor intensities in humans.
AB  - This study evaluated whether the intensity of previously smelled odors could
      unintentionally influence the subsequent judgement of odor intensity. The
      predicted context effect was based on the adaptation-level theory. Before and 25
      min after either WEAK or STRONG biasing odor concentrations, 51 subjects were
      required to rate the intensity of 10 different odor concentrations of California
      Orange Oil. After the WEAK bias, subjects judged the odor intensity as being
      stronger than they did after the STRONG bias. Thus the intensity of odors smelled
      25 min earlier can unintentionally influence subsequent odor intensity judgement.
      The findings are discussed in the light of two alternative explanations, namely,
      a central implicit memory process and a stimulus-level-based change at the
      peripheral level.

PMID- 9589162
TI  - Ultrastructural localization of amiloride-sensitive sodium channels and Na+,K(+)
      ATPase in the rat's olfactory epithelial surface.
AB  - Several studies have indicated that olfactory responses are impeded by amiloride.
      Therefore, it was of interest to see whether, and if so which, olfactory
      epithelial cellular compartments have amiloride-sensitive structures. Using
      ultrastructural methods that involved rapid freezing, freeze-substitution and low
      temperature embedding of olfactory epithelia, this study shows that, in the rat,
      this tissue is immunoreactive to antibodies against amiloride sensitive Na(+)
      channels. However, microvilli of olfactory supporting cells, as opposed to
      receptor cilia, contained most of the immunoreactive sites. Apices from which the
      microvilli sprout and receptor cell dendritic knobs had much less if any of the
      amiloride-antibody binding sites. Using a direct ligand-binding cytochemical
      method, this study also confirms earlier ones that showed that olfactory receptor
      cell cilia have Na+, K(+)-ATPase. It is proposed that supporting cell microvilli
      and the receptor cilia themselves have mechanisms, different but likely
      complementary, that participate in regulating the salt concentration around the
      receptor cell cilia. In this way, both structures help to provide the ambient
      mucous environment for receptor cells to function properly. This regulation of
      the salt concentration of an ambient fluid environment is a function that the
      olfactory epithelium shares with cells of transporting epithelia, such as those
      of kidney.

PMID- 9589163
TI  - Amiloride does not alter NaCl avoidance in Fischer-344 rats.
AB  - Fischer-344 (F-344) rats differ from other common rat strains in that they fail
      to show any preference for NaCl at any concentration in two-bottle preference
      tests. Because 100 microM amiloride partially blocks the NaCl-evoked chorda
      tympani (CT) response in electrophysiological studies, we tested NaCl preference
      (0.068-0.273 M) in F-344 rats with and without 100 microM amiloride solution as
      the solvent. A third group was tested with unadulterated NaCl solutions following
      CT transection. Amiloride had no significant effect on the NaCl preference
      aversion function, whereas CT transection significantly reduced NaCl avoidance.
      These results suggest that the amiloride-sensitive component of the NaCl response
      is not necessary for F-344 rats to display avoidance of NaCl, but the entire CT
      input is.

PMID- 9589164
TI  - Tonic GABAergic inhibition of taste-responsive neurons in the nucleus of the
      solitary tract.
AB  - The effects of gamma-aminobutyric acid (GABA) and the GABAA receptor antagonist
      bicuculline methiodide (BICM) on the activity of taste-responsive neurons in the
      nucleus of the solitary tract (NST) were examined electrophysiologically in
      urethane-anesthetized hamsters. Single neurons in the NST were recorded
      extracellularly and drugs (21 nl) were microinjected into the vicinity of the
      cell via a multibarrel pipette. The response of each cell was recorded to lingual
      stimulation with 0.032 M NaCl, 0.032 M sucrose, 0.0032 M citric acid and 0.032 M
      quinine hydrochloride (QHCl). Forty-six neurons were tested for the effects of
      GABA; the activity of 29 cells (63%) was inhibited by 5 mM GABA. Whether activity
      was elicited in these cells by repetitive anodal current stimulation (25 microA,
      0.5 s, 0.1 Hz) of the tongue (n = 13 cells) or the cells were spontaneously
      active (n = 13 cells), GABA produced a dose-dependent (1, 2 and 5 mM) decrement
      in activity. Forty-seven NST neurons were tested for the effects of BICM on their
      responses to chemical stimulation of the tongue; the responses of 28 cells (60%)
      were enhanced by 10 mM BICM. The gustatory responses of 26 of these cells were
      tested with three concentrations (0.2, 2 and 10 mM) of BICM, which produced a
      dose-dependent increase in both spontaneous activity and taste-evoked responses.
      Nine of these neurons were sucrose-best, seven were NaCl-best, eight were acid
      best and two responded best to QHCl. The responses to all four tastants were
      enhanced, with no difference among neuron types. For 18 cells that were tested
      with two or more gustatory stimuli, BICM increased their breadth of
      responsiveness to their two most effective stimuli. These data show that
      approximately 60% of the taste-responsive neurons in the rostral NST are
      inhibited by GABA and/or subject to a tonic inhibitory influence, which is
      mediated by GABAA receptors. The modulation of these cells by GABA provides a
      mechanism by which the breadth of tuning of the cell can be sharpened. Modulation
      of gustatory activity following a number of physiological changes could be
      mediated by such a GABAergic circuit.

PMID- 9589165
TI  - Replacement of receptor cells in the hamster vomeronasal epithelium after nerve
      transection.
AB  - Chemoreceptor cells in the vomeronasal and olfactory epithelium are replaced
      following experimentally induced degeneration. This study analyzes quantitatively
      the time course and degree of vomeronasal receptor cell replacement. Unilateral
      transection of the vomeronasal nerves in adult hamster was used to induce a
      retrograde degeneration of receptor cells in the vomeronasal organ. Histological
      measurement of both number of receptor cells and epithelial thickness were made
      for recovery times from 0 to 60 days. After nerve transection, there was a
      gradual degeneration of receptor cells, the number decreasing to 50% of control
      by day 2 and 16% by day 6. During days 7-15 maximum receptor cell replacement was
      observed. Cell number increased rapidly and reached a peak on day 15. At recovery
      times of 40-60 days, cell number returned to the control level. Epithelial
      thickness, however, decreased to 60-70% during the degeneration period (days 4-6)
      and did not return to control levels. After 40-60 days epithelial thickness
      remained at 70% of control. These results demonstrate that vomeronasal receptor
      cells are replaced following degeneration, but epithelial thickness does not
      return to control levels. These findings suggest that the number of replacement
      cells is not limited by the reduced thickness of the epithelium, and that
      recovery mechanisms may function to restore an optimum number of receptor cells.

PMID- 9589166
TI  - Modelling the human olfactory stimulus-response function.
AB  - Two models, derived from the equations of Michaelis-Menten and Hill, were adapted
      to olfaction. Their ability to model human olfactory stimulus-response
      relationships was compared with that of the classical laws of Fechner and
      Stevens. First, these four models were systematically compared on data available
      in the literature concerning 20 pure odorous compounds. At the lower
      concentrations of the odorous compound, the model of Stevens was found to be as
      good as the model of Hill. However, when the concentration range was extended
      further and included the concentration at half the maximum intensity, the model
      of Hill was found to be better. Second, the four models were tested on different
      parts of a true stimulus-response sigmoid curve with 5% noise added. The
      comparison confirmed the results obtained when experimental data were used.
      Third, the hypothesis that the psychophysical response is the sum of sigmoidal
      responses generated at the more peripheral parts of the olfactory system was
      examined, assuming a binomial distribution of receptor affinities. Within a very
      large range of variation in their characteristics, the sums of several sigmoids
      are indeed correctly modelled by Hill equations with exponents reflecting the
      distribution of receptor affinities.

PMID- 9589167
TI  - Cross-adaptation and molecular modeling study of receptor mechanisms common to
      four taste stimuli in humans.
AB  - Psychophysical cross-adaptation experiments were performed with two
      carbohydrates, sucrose (SUC) and fructose (FRU), and two sweeteners, acesulfame-K
      (MOD) and dulcin (DUL). Seven subjects were asked to match concentrations that
      elicited the same intensity as a sucrose reference (30 g/l). Cross-adaptation
      levels were calculated as the ratio of isointense concentrations measured for a
      given stimulus before and under adaptation. On average, cross-adaptation between
      SUC and FRU is low and apparently reciprocal. By contrast, cross-adaptation
      between SUC and MOD is clearly non-reciprocal: SUC adapts MOD significantly (24%,
      P < 0.005), but MOD fails to adapt SUC (2%, P < 0.79). Significant and reciprocal
      cross-enhancement is observed between DUL and MOD (approximately -20%, P < 0.03),
      and also between SUC and DUL (approximately -15%, P < 0.08). In parallel,
      molecular modeling of the four tastants was performed in order to look for the 12
      common binding motifs that were isolated on 14 other tastants in a previous
      study. SUC and FRU each display 10 out of the 12 binding motifs, whereas DUL and
      MOD only display four and five distinct motifs respectively and do not have any
      motif in common. Experimental cross-adaptation levels seem to correlate well with
      the number of motifs that molecules have in common. FRU and SUC share a majority
      of binding motifs and correlatively show mutual cross-adaptation. Four motifs of
      MOD are found among the 10 motifs of SUC, which may explain why SUC cross-adapts
      MOD but not vice versa. By contrast, DUL and MOD do not share any motif and do
      not cross-adapt. The various molecular mechanisms that may be responsible for
      cross-adaptation and/or cross-enhancement are discussed in light of our results.

PMID- 9589168
TI  - Lacustrine sockeye salmon return straight to their natal area from open water
      using both visual and olfactory cues.
AB  - Mechanisms of the amazing ability of salmon to migrate a long distance from open
      water to natal streams for spawning are still unknown. Lacustrine sockeye salmon
      (Oncorhynchus nerka) in Lake Toya offers an excellent model system for studying
      the orientation mechanism in open water, because mature fish return to the natal
      area with a high degree of accuracy. First we examined the percentage of fish
      returning to the natal area after they were released 7 km south of the natal
      area. Forty percent of control male mature fish and 25% of the fish blinded by
      injection of a mixture of carbon toner and corn oil into the eyeball were
      captured in the natal area within 5 days. Forty-four percent of fish with brass
      rings (control) and 31% of fish with NdFe magnetic rings which interfere with the
      magnetic cue were captured in the natal area within 3 days. These experiments
      suggested that, although the number of blinded fish captured in the natal area
      was less than that of the controls, the difference was not statistically
      significant. In the fish captured in the natal area within 3 or 5 days, fish
      which found the natal area using their olfactory cue after random swimming for a
      long time and returned to that area may be included. Hence we tracked fish
      telemetrically using an ultrasonic tracking system, and found that mature males
      released at a long distance (3.6 or 6.8 km) from the natal area swam straight to
      the vicinity of the natal area. Interference of the magnetic cue by the
      attachment of a magnetic ring did not affect their direct return. Blockage of the
      visual cue caused them to move randomly. These data suggest that lacustrine
      sockeye salmon return straight to the vicinity of the natal area using their
      visual cue and finally reach the exact homing point using their olfactory cue.

PMID- 9589169
TI  - Introduction: antisense oligonucleotides: strategies and successes.

PMID- 9589170
TI  - Current status of antisense DNA methods in behavioral studies.
AB  - The antisense DNA method has been used successfully to block the expression of
      specific genes in vivo in neuronal systems. An increasing number of studies in
      the last few years have shown that antisense DNA administered directly into the
      brain can modify various kinds of behaviors. These findings strongly suggest that
      the antisense DNA method can be used as a powerful tool to study causal
      relationships between molecular processes in the brain and behavior. In this
      article we review the current status of the antisense method in behavioral
      studies and discuss its potentials and problems by focusing on the following four
      aspects; (i) optimal application paradigms of antisense DNA methods in behavioral
      studies; (ii) efficiencies of different administration methods of antisense DNA
      used in behavioral studies; (iii) determination of specificity of behavioral
      effects of antisense DNA; and (iv) discrepancies between antisense DNA effects on
      behaviors and those on protein levels of the targeted gene.

PMID- 9589171
TI  - The child abuse lottery--will the doctor suspect and report? Physician attitudes
      towards and reporting of suspected child abuse and neglect.
AB  - OBJECTIVE: To assess the responsiveness and attitudes of medical practitioners to
      the reporting of suspected child abuse or neglect. To determine whether
      characteristics of the medical practitioner (specialist or generalist, rural or
      urban based, age since graduation, gender, having children of their own)
      influenced the responsiveness to reporting. METHOD: A survey of all members of
      the Australian College of Pediatrics in Queensland (Australia) and pediatric
      registrars at a tertiary training hospital in Brisbane (n = 124) and a random
      sample of Queensland general practitioners (n = 100). The survey requested
      demographic details, responses to three case vignettes suggestive of possible
      physical abuse or neglect, and details of suspected child abuse or neglect
      reporting behavior. RESULTS: There were a wide range of responses to the case
      vignettes, but responses did not vary between specialties. Forty-three percent of
      all doctors had at some stage considered a case as suspected child abuse or
      neglect and decided not to report despite a legal mandate to do so. General
      practitioners were more cautious towards reporting. The reasons for not reporting
      were multiple but highlighted perceived problems in the services available for
      the child and family once a report was made. CONCLUSIONS: There is need for
      continuing education of medical practitioners regarding symptoms and signs of
      physical abuse and the role of doctors in the multidisciplinary management of
      child abuse. To some extent children's outcome when presenting to medical
      practitioners as a result of child abuse or neglect is no better than a lottery,
      dependent on which doctor they happen to see.

PMID- 9589172
TI  - Psychopathology in the relatives of depressed-abused children.
AB  - OBJECTIVE: To determine if the type of symptomatology abused children manifest is
      related to family history of psychopathology. METHOD: Lifetime history of
      psychopathology was assessed in the relatives of 26 preadolescents--13 depressed
      abused (MDD-AB) and 13 depressed nonabused (MDD-NA) children. Rates of disorder
      in the relatives of these children were compared to published rates of
      psychopathology in relatives of 27 normal control (NC) children. Data were
      obtained on 104 first-degree relatives (MDD-AB = 25, MDD-NA = 29, NC = 50) and
      503 second-degree relatives (MDD-AB = 127, MDD-NA = 117, NC = 259). The Schedule
      for Affective Disorders and Schizophrenia was used to assess psychopathology in
      parents, and Family History method was used to obtain lifetime psychiatric data
      for all other relatives. RESULTS: When compared to first-degree relatives of NC
      children, first-degree relatives of MDD-AB children had approximately a nine-fold
      increased risk for major depression, and a three- to nine-fold increased risk for
      other disorders associated with the familial subtype of affective illness known
      as Depression Spectrum Disease (e.g., antisocial personality, alcohol and
      substance dependence). Similar findings were reported in second-degree relatives,
      and comparisons between the relatives of MDD-NA and NC children. CONCLUSION: The
      findings extend results of prior research and (1) suggest familial vulnerability
      factors influence the symptom profile of abused children; and (2) highlight the
      value of incorporating psychiatric formulations into multidisciplinary models of
      child abuse research and treatment programs.

PMID- 9589173
TI  - Self-concept and social competence of university student victims of childhood
      physical abuse.
AB  - OBJECTIVE: This study examined the impact of childhood physical abuse on self
      concept and social competency of older adolescents and assessed perception of
      parental relationships as a mediator for consequences of abuse on social
      adjustment. METHOD: College undergraduates (n = 660) completed: (a) the Social
      Skills Inventory (SSI), a measure of social competence, (b) the Self-Description
      Questionnaire-III (SDQ-III), a multidimensional measure of self-concept, (c) the
      parent scales of the Inventory of Parent and Peer Attachment (IPPA), a measure of
      perceived parental support, and (d) the Assessing Environments-III (AE-III), a
      retrospective report of family environment and parenting practices. RESULTS:
      Analyses, controlling for socioeconomic status and ethnicity, showed that a
      history of physical abuse was predictive of current self-concept, but did not
      predict social competence as an older adolescent. Further analyses lend support
      to a mediational model, suggesting that physical abuse has a negative impact on
      self-concept through its negative effect on parent-child relationships.
      CONCLUSIONS: The findings indicate that childhood physical abuse has a negative
      impact on the self-concept of the older adolescent. However, this impact can be
      better understood by investigating its potentially harmful effect on parent-child
      relationships. The impact of physical abuse on adolescents' social competence was
      not supported in this study.

PMID- 9589174
TI  - Long-term effects of childhood maltreatment history on gender-related personality
      characteristics.
AB  - OBJECTIVE: The aim of the study was to test the hypothesis that different types
      of gender-related personality attributes are associated with a past history of
      different types of childhood maltreatment. METHOD: A survey was administered to
      1,060 male soldiers and 305 female soldiers in the U.S. Army. The survey
      instrument included the Extended Personal Attributes Questionnaire (EPAQ) which
      is a self-assessment instrument of personality characteristics associated with
      gender, and includes measures of positive masculinity (self
      assertive/instrumental traits), positive femininity (expressive/interpersonal
      traits), negative masculinity (hyper masculine/macho traits), and negative
      femininity (subordination of self to others). The survey instrument also included
      the Childhood Trauma Questionnaire (CTQ), which contains scales measuring sexual
      abuse, physical-emotional abuse, physical neglect, and emotional neglect, and
      four questions on childhood sexual abuse developed for a national survey of U.S.
      adults. RESULTS: Negative masculinity was predicted by male gender, younger age,
      and childhood physical-emotional abuse. Negative femininity was predicted by
      physical-emotional abuse and sexual abuse. The relationship to sexual abuse was
      mainly evident for males. Positive femininity was positively correlated with
      sexual abuse for females and negatively correlated with sexual abuse for males.
      Positive masculinity was negatively correlated with emotional neglect for males
      but not for females. Positive femininity was negatively correlated with emotional
      neglect for both genders. CONCLUSIONS: Childhood abuse was associated with the
      presence of negative gender-related attributes; childhood neglect was associated
      with absence of positive gender-related attributes. Childhood physical abuse was
      associated with negative masculine attributes in both genders. Childhood sexual
      abuse was associated with positive feminine attributes in females, and negative
      feminine attributes in males. The finding for females is counterintuitive, and is
      discussed in the light of the clinical literature on certain types of adaptation
      to incest.

PMID- 9589175
TI  - Suicidal behavior and sexual/physical abuse among street youth.
AB  - OBJECTIVE: To examine the relationship between home life risk factors and suicide
      attempts among homeless and runaway street youth recruited from both shelters and
      street locations in Denver, CO; New York City; and San Francisco, CA. METHOD:
      Street youth 12-19 years old (N = 775) were recruited by street outreach staff in
      Denver, New York City and San Francisco in 1992 and 1993 and interviewed. Cross
      sectional, retrospective data were analyzed to examine the relationship between
      suicide attempts and antecedent home life variables. Logistic regression was used
      to identify factors predicting suicide attempts. RESULTS: Forty-eight percent of
      the females and 27% of the males had attempted suicide. The mean number of
      suicide attempts was 6.2 (SD = 12.9) for females and 5.1 for males (SD = 7.6).
      Among females, 70% reported sexual abuse and 35% reported physical abuse. Among
      males, 24% reported sexual abuse and 35% reported physical abuse. Sexual and
      physical abuse before leaving home were independent predictors of suicide
      attempts for females and males. Other home life factors hypothesized to be risk
      factors for suicide attempts were not significant. Interaction terms were not
      significant. Among street youth who were sexually or physically abused in this
      sample, the odds of attempting suicide were 1.9 to 4.3 times the odds of
      attempting suicide among those not sexually or physically abused. CONCLUSIONS:
      Interventions attempting to reduce risky behaviors in this population must
      include assessments of suicidal behaviors as well as components for assisting
      youth in dealing with the behavioral and emotional sequelae of physical and
      sexual abuse.

PMID- 9589176
TI  - PTSD as a mediator between childhood rape and alcohol use in adult women.
AB  - OBJECTIVE: Though a relationship between childhood sexual abuse and later alcohol
      use among women has been documented, little is known about the pathways that link
      these two variables. A tension reduction hypothesis posits that emotional
      distress precedes substance usage. PTSD symptomatology resulting from childhood
      sexual abuse is examined as a possible source of emotional distress that may
      cause subsequent alcohol use. METHOD: A sample of adult women was selected and
      interviewed on two occasions 1 year apart and childhood rape history, lifetime
      PTSD symptoms, and lifetime alcohol use were assessed. Path analytic techniques
      were used to evaluate the mediating role of PTSD symptoms on the relationship
      between childhood rape and subsequent alcohol use. RESULTS: A history of
      childhood rape doubled the number of alcohol abuse symptoms that women
      experienced in adulthood. Path analysis and cross-validation results demonstrated
      significant pathways connecting childhood rape to PTSD symptoms and PTSD symptoms
      to alcohol use. CONCLUSIONS: The results of the present study suggest that PTSD
      symptomatology which develops after childhood rape may be one of many variables
      that affect alcohol abuse patterns in women who were victims of childhood sexual
      abuse.

PMID- 9589177
TI  - Future outlook for child protection policies in Europe.

PMID- 9589178
TI  - Identification of child maltreatment with the Parent-Child Conflict Tactics
      Scales: development and psychometric data for a national sample of American
      parents.
AB  - OBJECTIVE: To create a parent-to-child version of the Conflict Tactics Scales,
      the CTSPC. METHOD: Description of the conceptual and methodological approaches
      used and psychometric data for a nationally representative sample of 1,000 U.S.
      children. RESULTS: (1) Improved Psychological Aggression and Physical Assault
      scales. (2) New Nonviolent Discipline scale, supplementary scale for Neglect, and
      supplemental questions on discipline methods and sexual abuse. (3) Reliability
      ranges from low to moderate. (4) Evidence of discriminant and construct validity.
      CONCLUSIONS: The CTSPC is better suited to measuring child maltreatment than the
      original CTS. It is brief (6 to 8 minutes for the core scales) and therefore
      practical for epidemiological research on child maltreatment and for clinical
      screening. Methodological issues inherent in parent self-report measures of child
      maltreatment are discussed.

PMID- 9589179
TI  - The association between child maltreatment and disabilities in a hospital-based
      epidemiological study.
AB  - OBJECTIVE: Circumstances of maltreatment and the presence of disabilities.
      METHOD: An electronic merger of the records of all pediatric patients. RESULTS:
      Detailed record analysis of circumstances of maltreatment and the presence of
      disabilities. CONCLUSIONS: Differences between the Hospital and Residential
      samples, maltreatment and perpetrator characteristics, disability/maltreatment
      relationships, and their implications for primary health care are discussed.

PMID- 9589180
TI  - A comparative survey of beliefs about "normal" childhood sexual behaviors.
AB  - OBJECTIVE: This study sought to collect data on what adults believe constitutes
      normal childhood sexual behaviors, and how variables, such as role, gender, and
      life experience might contribute to the formation of one's beliefs. METHODS: A
      survey describing 20 different scenarios of children under the age of 13
      interacting with themselves or other children in a sexual manner was administered
      to four groups of adults: sexual abuse experts; therapists involved in a sexual
      abuse training program; medical students attending a human sexuality program; and
      group facilitators of the human sexuality program. RESULTS: Behaviors that
      involved oral, vaginal, or anal penetration were judged by a majority of adults
      to be abnormal sexual behaviors in children under 13 years of age. Professionals
      working with sexually abused children rated certain sexual behaviors as more
      abnormal than adults participating in a human sexuality course. Both sexual abuse
      trainees and facilitators of the human sexuality course showed more directional
      biases than other groups, with trainees always rating behaviors in the direction
      of abnormal and facilitators always rating behaviors in the direction of normal.
      Females also judged many of the sexual behaviors to be more abnormal than males.
      CONCLUSIONS: Role and gender significantly influence what adults believe
      constitutes normal and abnormal childhood sexual behavior.

PMID- 9589181
TI  - Shared parenting: assessing the success of a foster parent program aimed at
      family reunification.
AB  - OBJECTIVE: There were two main objectives of the study: (1) To assess the
      effectiveness of a model of family reunification which united the role of parent
      aide and foster parent; and (2) to determine which characteristics of the
      families with children in care were associated with reunification. METHOD: A
      multisite project known as the Shared Parenting Project recruited families from
      five child protection agencies to participate in a program in which foster
      parents became extended rather than substitute families. Families were tested
      before the program began on a number of sociodemographic, psychological, and
      family measures. The success of the program was determined by whether the child
      was able to return home of if the program facilitated permanency planning. The
      success of the project was also examined by considering the relationship between
      returning home and a number of risk factors measured in the families with
      children in care. RESULTS: Very few families who met the criteria for the project
      could be recruited and only 31% of the participants completed the program and
      returned home. The process of permanency planning was facilitated in another 50%
      of the cases. The more stable families with less risk factors were more likely to
      complete the program successfully and to have their children return home.
      CONCLUSIONS: The results indicate that although the treatment model has excellent
      potential with less at-risk families it could not meet the treatment needs of the
      majority of families with children in foster care in the five child protection
      agencies. It is recommended that this model could be most helpful offered through
      parent aides attached to community support agencies that could provide respite
      care, support, and resources to families as needed thus avoiding the child having
      to be placed in care.

PMID- 9589182
TI  - Potential mediators of post-traumatic stress disorder in child witnesses to
      domestic violence.
AB  - OBJECTIVE: The aim was to examine variables that might mediate the incidence of
      Post-Traumatic Stress Disorder (PTSD) in child witnesses to domestic violence.
      These variables included age, gender, locus of control, self-blame, perception of
      threat, active versus palliative coping style, maternal emotional health plus
      aspects of the violence witnessed (intensity, frequency, age of child when first
      witnessing violence, and time since the last violent episode). METHOD: Following
      screening for other PTSD inducing experiences, a sample of 20 child witnesses to
      domestic violence, 15 matched control children, and their mothers were assessed
      using the following tools: The Straus Conflict Tactics Scale; the Child Post
      Traumatic Stress Reaction Index; the Nowicki-Strickland Locus of Control Scale;
      the General Health Questionnaire, and a Screening Questionnaire designed to
      elicit qualitative information from both children and mothers including data
      about any other potential PTSD inducing stressor the subject child may have been
      exposed to. RESULTS: None of the factors under examination were found to
      contribute significantly to the severity levels of Post-Traumatic Stress Disorder
      in relation to witness status. CONCLUSION: The small sample size of the study
      necessitates that the results be interpreted with caution. Nevertheless the
      findings indicate that the impact of witnessing domestic violence, in terms of
      PTSD, is not mediated by factors such as maternal emotional well-being, age and
      gender of the child, or the child's style of coping with parental conflict.
      Evidence that variables specifically related to the violence witnessed did not
      mediate the impact suggests that all domestic violence may have severe and long
      term impact on child witnesses.

PMID- 9589183
TI  - Residency training in child sexual abuse evaluation.

PMID- 9589184
TI  - Early and late advanced atrioventricular block in acute inferior myocardial
      infarction.
AB  - BACKGROUND: Advanced atrioventricular block is a frequent complication in
      patients with inferior acute myocardial infarction (AMI); in patients in
      hospital, it often occurs concurrently with other complications and is associated
      with high mortality. Very little information is available about early and late
      advanced atrioventricular block in inferior AMI. We hypothesized that the time of
      appearance of advanced atrioventricular block characterized by poor response to
      atropine requiring temporary pacemaker therapy may affect the prognosis of
      patients with inferior AMI. METHODS: We studied 51 patients with inferior AMI and
      advanced atrioventricular block characterized by poor response to atropine
      requiring temporary pacemaker therapy. According to pre-established
      electrocardiographic criteria and the time of appearance of the advanced
      atrioventricular block, patients were divided into two groups: an early block
      group consisting of 30 patients who developed advanced atrioventricular block
      during the first 24 h of inferior AMI, and a late block group consisting of 21
      patients who developed advanced atrioventricular block after the first 24 h of
      chest pain. RESULTS: The groups were similar regarding age, coronary risk
      factors, frequency of right ventricular infarction, QRS score, atrial and
      ventricular rates, the time of return to first-degree atrioventricular block,
      cardiac arrhythmias, heart failure and mortality. The early advanced
      atrioventricular block group included a greater number of men than did the late
      group (P = 0.017). CONCLUSION: These data suggest that the time of appearance of
      advanced atrioventricular block does not affect the prognosis of hospital
      patients with inferior AMI.

PMID- 9589185
TI  - Differences in histopathologic findings in restenotic lesions after directional
      coronary atherectomy or balloon angioplasty.
AB  - BACKGROUND: Directional coronary atherectomy (DCA) and balloon angioplasty
      (percutaneous transluminal coronary angioplasty, PTCA) differ in their method of
      dilating stenotic vessels. It is not known whether there is any morphologic
      difference between restenotic lesions that occur after DCA and those occurring
      after PTCA. METHODS: To evaluate histopathologic differences between restenotic
      lesions after DCA or PTCA, we reviewed coronary atherectomy specimens excised
      from 37 patients with stable angina. Patients were classified into three groups:
      those with restenotic lesions after DCA (n = 8), those with restenotic lesions
      after PTCA (n = 14), and those with primary lesions (n = 15). Specimens were
      analyzed immunohistochemically using monoclonal antibodies specific for smooth
      muscle cells (HHF35), endothelial cells (CD31), macrophage-derived foam cells
      (CD6B) and cell replication activity (Ki-67). In seven patients undergoing repeat
      DCA, de novo plaques and restenotic plaques were compared. RESULTS: Stellate
      smooth muscle cell (S-SMC) content in restenotic lesions after DCA (87%) was
      significantly greater than that in primary lesions (40%; P = 0.032) and that in
      restenotic lesions after PTCA (43%; P = 0.045). Foam cells tended to be more
      prevalent in primary lesions (67%) than in restenotic lesions after DCA (25%; P =
      0.062) or after PTCA (36%; P = 0.10). Restenotic lesions after DCA had more S-SMC
      proliferation and fewer foam cells than did primary lesions. There were no
      differences in the presence of thrombus, calcification, cholesterin, hemosiderin,
      the percentage of HHF35-positive cells or Ki-67-positive cells, or
      neovascularization among the three groups. CONCLUSIONS: Smooth muscle cell
      proliferation may have an important role in the development of restenosis after
      DCA. Fewer foam cells are present in restenotic lesions after DCA or PTCA than
      are present in primary lesions.

PMID- 9589186
TI  - Age-related development of atherosclerotic plaque stress: a population-based
      finite-element analysis.
AB  - BACKGROUND: In order to identify those age-related factors in the development of
      coronary atherosclerosis that would affect the stability of the plaque system, we
      have developed idealized, finite-element, cross-sectional models of the arterial
      wall and associated lesions, derived from population-based data. METHODS: The
      physical development and morphology of coronary plaques was documented in the
      Pathobiological Determinants of Atherosclerosis in Youth histological study.
      Using this database, finite-element analysis models were created for five age
      groups (15-19, 20-24, 25-29 and 30-34 years) and for the 25 largest lesions.
      Cosmos (Structural Research, Inc., Los Angeles, California, USA) was used to
      create and analyze the models. RESULTS: The area of greatest stress shifted from
      the intima opposite the lesion in the 15-19 years age group to the edge of the
      cap and adjacent healthy tissue in the later age groups. Increasing age had a
      strong positive correlation with the shoulder stress level (r = 0.95) and the per
      cent stenosis correlated well with shoulder stress (r = 0.99, P < 0.002).
      Increasing the cap stiffness from a soft cap to a fibrous cap in the 30-34 year
      age group model resulted in a localized increase in shoulder surface stress by
      10%. A calcified cap increased this shoulder surface stress by 30%. CONCLUSIONS:
      This finite-element analysis of the population-based data shows that the increase
      in stress appears to be closely related to the impaired load-bearing capability
      of the lipid pool that develops with age. The shoulder area of the lesion has
      been shown to be the location of most of the plaque fractures.

PMID- 9589187
TI  - Coronary flow velocity patterns immediately after reperfusion reflect the
      pathologic characteristics of reperfused myocardium in canine models of acute
      myocardial infarction.
AB  - BACKGROUND: It is difficult to evaluate the extent of myocardial injury after
      successful reperfusion following acute myocardial infarction (AMI). We
      investigated the relationship between the coronary flow velocity pattern
      immediately after reperfusion and pathologic characteristics after myocardial
      reperfusion injury in dogs. METHODS: We measured distal coronary flow velocity
      variables in the left circumflex coronary artery in a canine model of AMI (n =
      12) 10 min after the release of a clamp (3-10 h clamp procedure) using a 0.35 mm
      Doppler guide-wire. Dogs were divided into two groups according to presence or
      absence of early systolic retrograde coronary flow. Hearts were excised 2 h after
      reperfusion and examined histopathologically. RESULTS: The clamping time tended
      to be longer in dogs with early systolic retrograde coronary flow. Neutrophil
      infiltration was observed in the myocardium of dogs without systolic retrograde
      flow (n = 9); hemorrhage was rarely detectable and the myocardium maintained a
      bundle form. However, the bundle form of the myocardium became rough, and the
      severity of the incidence of hemorrhage tended to increase as the ratio of the
      diastolic coronary flow velocity to systolic velocity (DSVR) decreased. Vacuolar
      degeneration of the myocardium was also observed in hearts with a relatively low
      DSVR. In the group with systolic retrograde flow (n = 3), hearts were
      characterized by coagulation necrosis, marked vacuolar degeneration of the
      myocardium and diffusely distributed red cells in the intermyocytes. Systolic
      antegrade flow velocity was much reduced in this group, resulting in a markedly
      increased DSVR. These findings appeared to be related to severe myocardial
      damage. CONCLUSIONS: Coronary flow velocity patterns immediately after successful
      reperfusion appear to reflect the pathologic characteristics of the reperfused
      myocardium in dogs with AMI.

PMID- 9589189
TI  - Thrombin inhibition and intracoronary thrombus formation: effect of polyethylene
      glycol-coupled hirudin in the stenosed, locally injured canine coronary artery.
AB  - BACKGROUND: Adhesion and aggregation of platelets at sites of intimal injury are
      accompanied by local thrombin generation and conversion of fibrinogen to
      insoluble fibrin. As the long-acting thrombin inhibitor, polyethylene glycol
      coupled hirudin (PEG-hirudin), would be expected to interrupt this process by
      inhibiting the action of thrombin on platelets and fibrinogen, its effect on
      intracoronary thrombus formation, coagulation, platelet function, and duration
      and intensity of bleeding events was investigated. METHODS: Cyclic coronary flow
      reductions (CFRs) were induced in the left anterior descending coronary artery of
      24 anaesthetised mongrel dogs by mechanical injury of the endothelium combined
      with critical stenosis. There were four treatment regimens (six dogs per group):
      Control (isotonic saline); PEG 0.08 (0.15 mg/kg bolus + 0.08 mg/kg.h infusion);
      PEG 0.15 (0.30 mg/kg bolus + 0.15 mg/kg.h infusion); PEG 0.30 (0.60 mg/kg bolus +
      0.30 mg/kg.h infusion). RESULTS: A linear increase in steady-state plasma
      concentrations to 35.4 +/- 1.6 antithrombin units (ATU)/ml, 59.2 +/- 3.0 ATU/ml
      and 112.7 +/- 8.4 ATU/ml was achieved with the three doses of PEG-hirudin. The
      activated partial thromboplastin time (APTT) was increased 1.7-fold with PEG
      0.08, 1.9-fold with PEG 0.15 and 2.2-fold with PEG 0.30. The frequency of CFRs
      during the first hour after drug administration was diminished by about 20% with
      all three doses of PEG. During the second hour, CFRs were decreased by 61% in all
      treated groups. Thrombin-induced platelet aggregation was completely abolished by
      all PEG-hirudin regimens. Buccal bleeding time and blood loss were not increased
      after either treatment. CONCLUSION: In this canine model of coronary artery
      stenosis, the thrombin inhibitor, PEG-hirudin, effectively reduces platelet
      dependent thrombus formation without interfering with primary haemostasis.

PMID- 9589188
TI  - Effects of OG-VI, a nucleoside/nucleotide mixture, on stunned myocardium in dogs:
      is the adenosine A1 receptor involved?
AB  - BACKGROUND: OG-VI is a solution composed of 30 mmol/l inosine, 30 mmol/l sodium
      5'-guanylate, 30 mmol/l cytidine, 22.5 mmol/l uridine and 7.5 mmol/l thymidine;
      it limits myocardial stunning in dogs. We examined whether adenosine A1 receptors
      were involved in the mechanism of action of OG-VI. METHODS: Dogs anesthetized
      with pentobarbital were subjected to 20 min of left anterior descending coronary
      artery ligation followed by 30 min of reperfusion. Saline, OG-VI in several
      doses, adenosine or inosine was infused at 0.1 ml/kg/min, starting 30 min before
      the ischemia. In some experiments, 1 or 3 mg/kg 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, was
      injected intravenously 15 min before the start of the OG-VI infusion. The
      percentage myocardial segment shortening (%SS) was measured by sonomicrometry.
      The tissue concentration of ATP was measured in the 30-min-reperfused hearts.
      RESULTS: In the saline group, %SS that had been decreased by ischemia returned
      toward pre-ischemic values after reperfusion, although the metabolic recovery was
      incomplete, with a low concentration of ATP. The %SS was almost completely
      restored by 12 and 1.2 mumol/kg/min OG-VI, but 0.4 mumol/kg/min was less
      effective. Administration of adenosine or inosine did not modify the changes in
      %SS during ischemia/reperfusion. Pretreatment with DPCPX worsened the recovery of
      %SS during reperfusion after ischemia in both the saline and the OG-VI groups.
      Infusion of DPCPX (3 mg/kg) with saline caused the animals to die shortly after
      the onset of ischemia. However, the enhancement of %SS recovery during OG-VI
      reperfusion was observed in the presence of DPCPX. CONCLUSION: OG-VI improves the
      recovery of %SS during reperfusion after brief ischemia in a dose-dependent
      manner. This effect is not brought about by stimulation of adenosine A1
      receptors.

PMID- 9589190
TI  - Hemodynamic changes determine the efficacy of thrombolysis: results from an in
      vitro flow model.
AB  - BACKGROUND: The efficacy of thrombolytic therapy might be influenced by changes
      in the hemodynamic status. The aim of the study was to examine whether changes in
      perfusion pressure could affect the time to reflow in an in-vitro model. METHODS:
      The in-vitro flow system comprised flexible plastic tubes that enclosed a blood
      clot formed in one of the circuit arms. Streptokinase (125,000 U) or saline
      (control) was injected from a proximal side branch to induce thrombolysis. The
      protocol comprised four treatments: A, perfusion pressure 150/90 mmHg with
      streptokinase infusion; B, perfusion pressure 150/90 mmHg with saline; C,
      perfusion pressure 120/60 mmHg with streptokinase; D, perfusion pressure 120/60
      mmHg with saline. Reflow was defined as flow restoration determined by the
      ultrasonic flowmeter. RESULTS: Successful recanalization was obtained in six of
      six samples subjected to treatment A (100%), two of seven samples subjected to
      treatment B (28%), three of five samples subjected to treatment C (60%) and none
      of six samples subjected to treatment D (0%). Time to reflow was 23 +/- 11 min
      with treatment A, 76 +/- 24 min with treatment B, 66 +/- 25 min with treatment C,
      and > 90 min with treatment D. CONCLUSIONS: Our data suggest that the hemodynamic
      status determines the efficacy of streptokinase-induced thrombolysis, and that
      spontaneous clot lysis is more likely to occur at greater perfusion pressures. It
      is conceivable that the hypotensive reaction induced by streptokinase in the
      clinical setting may adversely affect angiographic patency, compared with that
      observed with other lytic agents such as tissue-type plasminogen activator.

PMID- 9589192
TI  - New Q waves do not always a new infarct spell: right bundle branch block
      dependent Q waves simulating infarct extension.
AB  - We present the electrocardiograms of three patients, representative of 14, with
      acute anterior wall infarction in whom, in contrast to current understanding, the
      appearance of right bundle branch block was associated with a shift of the
      initial vector of depolarization that resulted in 'new' Q waves in V1-V2 that
      mimicked extension of necrosis. This little-known electrocardiographic phenomenon
      should be kept in mind when consideration is given to attempts at reperfusion.

PMID- 9589191
TI  - Association between plasma homocysteine and peripheral arterial disease in older
      persons.
AB  - BACKGROUND: Plasma homocysteine is a risk factor for peripheral arterial disease.
      METHODS: In a cross-sectional study design we investigated the association
      between plasma homocysteine, vitamin B12 and folate concentrations, and the
      prevalence of peripheral arterial disease in 158 men and 362 women, mean age 81
      +/- 8 years. RESULTS: Univariate analysis showed that plasma homocysteine,
      vitamin B12 (inverse association) and folate (inverse association) concentrations
      and increased plasma homocysteine and low or indeterminate vitamin B12
      concentrations were risk factors for peripheral arterial disease in older men and
      women. Stepwise multiple logistic regression analysis showed that significant
      independent risk factors for peripheral arterial disease were a greater value of
      plasma homocysteine (P = 0.0001; odds ratio = 1.125) and a low value of plasma
      folate (P = 0.0001; odds ratio = 0.709). CONCLUSIONS: High plasma concentrations
      of homocysteine and low plasma concentrations of folate are significant
      independent risk factors for peripheral arterial disease in older men and women.

PMID- 9589193
TI  - Bibliography current world literature.

PMID- 9589194
TI  - The seriously burned child: resuscitation through reintegration--1.

PMID- 9589195
TI  - Sunscreens. Use and misuse.
AB  - Although sunscreens are widely available and in common use, surveys show that an
      average of only half of the people on a beach on a given day wear sunscreens.
      Many people go to the beach to get or maintain a suntan, but many people also
      leave their skin unprotected. This article discusses the proper use of
      sunscreens, common misunderstandings, and how unprotected long-term exposure to
      the sun can effect your skin.

PMID- 9589196
TI  - The benefits and risks of long-term PUVA photochemotherapy.
AB  - In 1974 a new photobiologic principle i.e. light + drug, called photochemotherapy
      was discovered in Boston and immediately confirmed in Vienna. Psoralen + UVA
      (PUVA) photochemotherapy has now been applied to the treatment of more than 24
      heterogeneous groups of diseases, especially psoriasis and mycosis fungoides.
      After 24 years of experience in thousands of patients with psoriasis and 23 other
      skin disorders, virtually the only risk is the development of squamous-cell
      carcinomas. This risk is low with two exceptions: previous history of treatment
      with ionizing radiation or inorganic trivalent arsenic, and patients with
      recalcitrant psoriasis who require continuous treatment for many years. In a
      recent report from a large USA clinical trial, melanoma developed in a few
      patients with psoriasis treated with PUVA. This prospective clinical trial did
      not have a control population, and therefore, the conclusion that PUVA can cause
      melanoma is tentative.

PMID- 9589197
TI  - Immunosuppressive agents in dermatology. An update.
AB  - Azathioprine, cyclophosphamide, methotrexate, and cyclosporine are the
      immunosuppressive agents most commonly used by dermatologists. Azathioprine has a
      relatively good safety profile and is therefore often preferred for the treatment
      of chronic eczematous dermatitides and bullous disorders. Awareness of the role
      of genetic polymorphisms in its metabolism can increase the efficacy and safety
      of this drug. Cyclophosphamide is an antimetabolite that has a more rapid onset
      of immunosuppressive effect than azathioprine, but has significant short-term and
      long-term toxicity. It is of use in fulminant, life-threatening cutaneous
      disease. Methotrexate is an antimetabolite that has significant anti-inflammatory
      activity. Despite its hepatotoxicity, its role in inflammatory dermatoses is
      broadening. Likewise, the role of cyclosporine is being expanded. This drug has
      potent T-cell inhibitory effects secondary to interference with intracellular
      signal transduction. Given the evidence for cumulative renal toxicity, it
      currently has a role in the short-term treatment of refractory psoriasis and
      atopic dermatitis, as well as in select inflammatory dermatoses. Familiarity with
      disease-specific clinical efficacy, side-effect profile, and dosage allows the
      successful and judicious use of these drugs in dermatologic disorders.

PMID- 9589198
TI  - New directions in surgical therapy.
AB  - Surgical dermatology continues to evolve rapidly. The field is blessed with a
      number of bright and enthusiastic young surgeons who are willing to spend to
      necessary time investigating new techniques. The horizon has changed dramatically
      over the last 5 years and promises to change even more in the years to come.

PMID- 9589199
TI  - Advances in dermatologic lasers.
AB  - Lasers continue to fundamentally redefine the nature of dermatologic practice.
      Recent advances in dermatologic lasers have focused on refining the process of
      selective photothermolysis, as well as evaluating new devices and treatment
      indications. Despite the current multiplicity of available lasers and associated
      marketing claims, what is perhaps most lacking are data comparing the efficacy of
      different lasers that can be used to treat the same condition, and data on the
      long term benefits of laser treatment.

PMID- 9589200
TI  - Vaccines for melanoma. Design strategies and clinical results.
AB  - Melanoma vaccines represent a novel and potentially effective method of slowing
      the progression of melanoma. This article discusses the importance in the design
      of vaccines for melanoma, the relative advantages and disadvantages of this
      approach, and summarizes the results of the most important clinical trials
      conducted to date with this vaccine.

PMID- 9589201
TI  - The risks of systemic corticosteroid use.
AB  - Because of their potent antiinflammatory and immunosuppressive properties,
      systemic corticosteroids are used to modify a vast array of diseases. This class
      of drugs, however, has the potential to produce multiple adverse effects
      presenting the dermatologist with difficult decisions in the management of
      patients with potentially steroid responsive disorders. This article reviews the
      side effects of systemic corticosteroids, comments on strategies to minimize
      these side effects, as well as, outlining suggested mechanisms by which
      physicians may minimize the risks of medical legal consequences owing to adverse
      reactions to these drugs.

PMID- 9589202
TI  - Transdermal drug delivery. Clinical aspects.
AB  - The delivery of drugs into and through the skin is a recognized and effective
      means of therapy for dermatologic, regional, and systemic disease. The selection
      of drug candidates and the rational design of suitable formulations depends upon
      the biological make-up of the skin's barrier, and the physiochemical interactions
      between the membrane, the delivery system technology, and the active agent. This
      article summarizes the state of the art and examines more recent developments
      that are the subject of considerable research at this time. In addition, the
      potential to use the skin as a portal for noninvasive clinical chemistry (e.g.,
      for glucose monitoring in diabetics) is discussed.

PMID- 9589203
TI  - Advances in the management of cutaneous T-cell lymphoma.
AB  - This article focuses on the management of specific T-cell components of cutaneous
      T-cell lymphomas. Advances in the management of these lymphomas are evaluated and
      classified. New treatment strategies and therapies are discussed.

PMID- 9589204
TI  - Radiotherapy in the treatment of dermatologic malignancies.
AB  - Although advances in surgical techniques, particularly micrographic surgery, have
      considerably expanded its role in the management of dermatologic malignancies,
      radiotherapy remains of considerable value. Its use should be considered in
      particular for the appropriate solid tumors in older patients, for metastatic
      disease, and for the more radioresponsive tumors including Merkel cell carcinoma,
      Kaposi's sarcoma, and the cutaneous lymphomas.

PMID- 9589205
TI  - Extemporaneous compounding. The end of the road?
AB  - Extemporaneous compounding has long been a part of dermatology. It has served to
      produce niche therapies that otherwise would have been poorly treated with
      available drugs. Increasingly however, the unpredictable nature of compounded
      medications, both in effectiveness, as well as safety and stability of such
      products, has diminished the use of this approach. The increasing availability of
      new pharmaceutical drugs that fill these niches more effectively, coupled with
      economic and legal concerns over the practice of compounding make it a tradition
      with an increasingly limited role in dermatology today. It is safe to predict
      that in the near future, compounding will virtually disappear from dermatology,
      as it already has from virtually all other medical specialties.

PMID- 9589206
TI  - Compounding is still appropriate in clinical practice.
AB  - Compounding involves the mixing of an active drug and preservatives into an
      appropriate base, or vehicle. All topical drugs are compounded. In the past, most
      patients with skin disease were treated with "custom made" topical preparations
      prescribed by their dermatologist; more recently, responsibility for this has
      been ceded to pharmaceutical companies that manufacture standardized products
      created from a set formula. Unfortunately, these commercial entities often do not
      supply all the medications needed by our patients, and under these circumstances,
      dermatologists can and should maintain the knowledge to extemporaneously compound
      these preparations themselves.

PMID- 9589207
TI  - Systemic retinoids. What's new?
AB  - Despite major advances in the molecular biology and pharmacology of retinoids, no
      new compound has been developed for systemic use. This article addresses some
      questions related to the indications of oral retinoids already on the market,
      e.g. isotretinoin, acitretin, as well as tretinoin, reviews some recently
      reported undesirable effects, and discusses the recent concepts generated by
      basic research that may lead to new drugs to be used in pharmacology.

PMID- 9589208
TI  - Hair regrowth. Therapeutic agents.
AB  - Today there are new classes of hair growth promotors with proven efficacy. This
      article reviews the current state of the art agents for treatment of two of the
      most common forms of hair loss encountered in clinical practice, androgenetic
      alopecia and alopecia areata. Current therapeutic strategies are based on recent
      advances in the understanding of disordered hair growth. Practical treatment
      protocols are presented.

PMID- 9589210
TI  - How to heal a wound fast.
AB  - An overview of the therapeutic possibilities of acute wounds, ulcers, and
      infected or colonized wounds is given. This article reviews therapeutic
      approaches and nonsurgical dermatologic treatments in particular. The types of
      wounds discussed include acute wounds, infected acute wounds, chronic wounds,
      infected and colonized chronic wounds, and incurable wounds.

PMID- 9589209
TI  - Photoaging and tretinoin.
AB  - Premature skin aging caused by repeated exposure to solar radiation is called
      photoaging. Although once considered an irreversible process, it is now
      established that photoaging can be treated by topical tretinoin. Both from
      carefully designed controlled clinical studies; and basic investigations into the
      mechanism by which tretinoin improves photoaged skin, our understanding of
      photoaging has been enhanced. This article highlights some of these studies which
      have contributed to our knowledge.

PMID- 9589211
TI  - Interferons in dermatology. Present-day standard.
AB  - Since the first clinical trials in the early 1980s with recombinant interferon,
      it was possible to show for a variety of indications that cytokines, especially
      interferons, at certain doses and at respective intervals, when applied in
      combination with other pharmaceutical compounds open new powerful therapeutic
      possibilities. Worldwide, recombinant interferon is licensed, especially in
      dermato-oncology, for the indication of HIV-associated Kaposi's sarcoma,
      cutaneous T-cell lymphoma, and recently for adjuvant therapy of high-risk
      malignant melanoma. Recombinant interferon is at present not licensed for
      dermatologic indication (septic granulomatosis). At the end of our century the
      indication spectrum for interferons as monotherapy and as combination therapy
      will undoubtedly be extended. Larger and controlled studies will prove the
      importance of interferons in dermato-oncology as well as in inflammatory and
      infectious dermatoses. The combination of interferons with standard therapies
      will surely be of the utmost importance in dermatotherapy.

PMID- 9589212
TI  - Vitiligo. Therapeutic advances.
AB  - Vitiligo often induces severe cosmetic disfigurement in patients. Both
      nonsurgical (medical) and surgical approaches for repigmenting vitiliginous
      macules are described (Table 1). Currently PUVA therapy appears to be the best
      method in providing reasonable hope for achieving repigmentation. Guidelines for
      both topical and systemic PUVA are available. Furthermore, surgical graft of
      autologous epidermal sheet or cultured melanocytes (often combined with
      keratinocyte co-culture) can be introduced to repigment the depigmented areas
      where PUVA is ineffective. PUVA therapy after autologous skin graft can enhance
      the repigmenting efficiency. Although PUVA with or without surgical procedure
      represents a useful tool in vitiligo treatment, we should look for other new
      treatment modalities based upon better understanding of basic biology of melanin
      pigmentation and pathophysiology of this disease. A recent development of topical
      pseudocatalase and calcium application combined with UVB phototherapy may be one
      of the typical examples in this respect. Many patients are significantly affected
      psychologically by the disease. Physicians should attempt to assess the degree of
      psychological impairment caused by vitiligo. Supportive care should always be
      offered if necessary in order to minimize these problems appropriately. In
      closing, normal skin of vitiligo patients can be totally depigmented by
      monobenzyl ether of hydroquinone in order to match the skin color in certain
      generalized vitiligo patients. There is a recent case report of extensive
      vitiligo with rapid repigmentation of depigmenting vitiliginous skin within a few
      weeks after discontinuing successful depigmentation therapy by monobenzyl ether
      of hydroquinone.

PMID- 9589213
TI  - Advances in antiviral therapy in dermatology.
AB  - For years, investigators have sought to control viral transmission and to find
      appropriate treatment for people who have viral infections. Exposure control
      (e.g. vaccines, sanitation, vector control, blood testing, condoms/abstinence,
      and education) has been extremely important in management of viral spread.
      Several antiviral agents have received approval from the United States Food and
      Drug Administration over the past few years. There continues to be extensive
      research on new antiviral agents as well as new vaccines to control viral disease
      and spread. Most viral diseases continue to be treated symptomatically; however,
      the discovery of new and improved antiviral agents has added great power to our
      ability to treat certain hard-to-control viruses that plague patients.

PMID- 9589214
TI  - Reactions and interactions of some commonly used systemic drugs in dermatology.
AB  - This article deals with the main interactions and adverse effects of some drugs
      that are used daily by dermatologists. It includes tetracyclines and Minocycline
      in the treatment of acne; antimalarials and discoid lupus; dapsone; thalidomine;
      oral retinoids; methotrexate and cyclosporine. Several of these drugs are
      discussed.

PMID- 9589215
TI  - Infants' response to the audible and visible properties of the human face: II.
      Discrimination of differences between singing and adult-directed speech.
AB  - Human infants' responsiveness to the audible and visible features of human faces
      was studied by habituating them to a person speaking a prepared script in an
      adult-directed manner and then administering a series of separate test trials
      where a person could be seen, heard, or seen and heard singing. When habituated
      to a female person speaking in an adult-directed manner and tested with a singing
      female 4, 6, and 8-month-old infants responded to the audible, visible, and
      bimodal changes, whereas 3-month-old infants only responded to the visual and
      bimodal changes. In contrast, when habituated to a male person speaking in an
      adult-directed manner and tested with a singing female, all age groups
      discriminated all three types of changes. These findings demonstrate that infants
      are responsive to differences between low- and high-prosody content inherent in
      both the facial and vocal characteristics of the human face and that, whereas
      responsiveness to the visible and bimodal features associated with differences
      between adult-directed speech and singing is present as early as 3 months of age,
      responsiveness to the audible features emerges between 3 and 4 months of age
      depending on whether gender differences are present as well.

PMID- 9589216
TI  - Distractibility during infants' examining and repetitive rhythmic activity.
AB  - The goal of this study was to assess the role of examining and repetitive
      rhythmic activity in infants' exploration of novel objects. Sixteen 8-month-old
      infants played with novel toys as auditory-visual slide distractors occurred on
      one side at random intervals. The results showed that examining, but not
      repetitive activities, declined with exposure to the objects. They also showed
      that infants had different patterns of distractibility during examining and
      repetitive rhythmic activities. The infants were slower to turn to the distractor
      if they were examining the toy than if they were engaged in other activity, but
      the probability of a response did not differ. In contrast, when engaged in
      repetitive rhythmic activity, infants were less likely to respond to the
      distractor than when engaged in other activities, including examining; the speed
      with which they responded, however, did not differ. The results suggest that,
      during these two activities, the mechanisms for resisting distraction are quite
      different.

PMID- 9589217
TI  - Postnatal foraging demands alter adrenocortical activity and psychosocial
      development.
AB  - Mother squirrel monkeys stop carrying infants at earlier ages in high-demand (HD)
      conditions where food is difficult to find relative to low-demand (LD)
      conditions. To characterize these transitions in psychosocial development, from
      10- to 21-weeks postpartum we collected measures of behavior, adrenocortical
      activity, and social transactions coded for initiator (mother or infant), goal
      (make-contact or break-contact), and outcome (success or failure). Make-contact
      attempts were most often initiated by HD infants, but mothers often opposed these
      attempts and less than 50% were successful. Break-contact attempts were most
      often initiated by LD infants, but mothers often opposed these attempts and fewer
      LD than HD infant break-contact attempts were successful. Plasma levels of
      cortisol were significantly higher in HD than LD mothers, but differences in
      adrenocortical activity were less consistent in their infants. HD and LD infants
      also spent similar amounts of time nursing on their mothers and feeding on solid
      foods. By rescheduling some transitions in development (carry-->self-transport),
      and not others (nursing-->self-feeding), mothers may have partially protected
      infants from the immediate impact of an otherwise stressful foraging task.

PMID- 9589218
TI  - Infants' earliest sleep/wake organization differs as a function of delivery mode.
AB  - The sleep/wake states of newborn infants were investigated as as a function of
      vaginal and C-section delivery. The subjects were 51 normal full-term infants: 26
      vaginally delivered, 12 delivered by emergency C-section, and 13 delivered by
      elective C-section. Their sleep states and wakefulness were continuously recorded
      from the time of birth throughout their stay in the hospital, that is, the first
      2 postnatal days for the vaginally delivered infants and 5 days for the C-section
      infants. Sleep was recorded using the automated Motility Monitoring System, which
      permits 24-hr recordings without instrumentation of the subject. During the 1st
      postnatal day, both C-section groups showed state patterns that differed
      significantly from those of the vaginally delivered infants. Analyses for single
      states indicated that both C-section groups had significantly less active sleep,
      and the elective group had more wake and more sleep--wake transition than the
      vaginal group. The two C-section groups did not differ significantly on any
      measure. Only the vaginally delivered infants showed significant day/night
      differences during the first 2 days, with more wakefulness, shorter mean sleep
      periods and shorter longest-sleep periods during the daytime on both days. The
      results of this study indicate that the earliest postnatal sleep patterns differ
      and the diurnal sleep rhythm is disrupted as a result of surgical delivery.

PMID- 9589219
TI  - Maternal cradling and infant nipple preferences in rhesus monkeys (Macaca
      mulatta).
AB  - This study investigated lateral biases in nipple preferences, maternal cradling,
      carrying, and retrieval in 41 rhesus macaque (Macaca mulatta) mother-infant dyads
      living in two captive social groups. Observations were made during the first 6
      weeks of infant life using a combination of scan sampling and ad-libitum sampling
      techniques. Infants exhibited a significant left-nipple preference in the first
      weeks of life but the bias decreased with infant age. Mothers showed a left-arm
      bias in carrying their infants but no significant lateral bias in cradling or
      retrieval. Our results suggest that the left-side cradling bias reported in
      studies of humans and some other primates reflects a bias in the infant's nipple
      preference rather than in maternal behavior. The infants' preference for the left
      nipple is consistent with both Salk's (1960) heartbeat hypothesis and with more
      recent hypotheses linking this lateral bias with brain asymmetry and hemispheric
      specialization for mother-infant communication.

PMID- 9589220
TI  - Behavioral responsitivity to dopamine receptor agonists after extensive striatal
      dopamine lesions during development.
AB  - Dopamine (DA) receptor responsitivity was investigated in adult rats that
      received intrastriatal (i.s.) injections of 6-OHDA (20 micrograms per striatum)
      on day of birth or postnatal Day 1 (Day 0/Day 1). Neonatally lesioned rats
      exhibited self-biting behavior and increases in stereotypic gnawing following
      treatment with the mixed D1/D2 receptor agonist apomorphine (0.32-3.2 mg/kg) or
      the D1-like receptor agonist SKF38393 (10 mg/kg). Increases in locomotor
      activity, rearing, and paw treading were also observed in the lesioned rats after
      SKF38393 (1-10 mg/kg) treatment. The incidences of the prototypical D1 receptor
      mediated behaviors, grooming and abnormal perioral movements (i.e., oral
      dyskinesias) were not increased in the lesioned rats. However, the low dose (0.32
      mg/kg) of apomorphien as well as all doses of the D2-like receptor agonist
      quinpirole (0.32-3.2 mg/kg) induced grooming in the lesioned rats, which was not
      observed in nonlesioned control rats. Autoradiographs of [3H]mazindol binding to
      high affinity DA uptake sites revealed an extensive loss of DA terminals in the
      striata of the neonatally lesioned rats. These data suggest that near-total (> or
      = 95%) DA depletions on Day 0/Day 1 result in long-term alterations in the
      functional sensitivity of DA receptors, as well as possible changes in the
      interactions between D1 and D2 receptors. Comparisons of these results with those
      seen following lesions of the early-developing DA system ("patch-selective"
      lesions) and lesions made at other time points will be discussed.

PMID- 9589221
TI  - Prenatal visual experience influences the development of turning bias in bobwhite
      quail chicks (Colinus virginianus).
AB  - This study examined the effects of prenatal sensory experience on the development
      of turning bias in a precocial avian species (bobwhite quail). Control tests with
      naive bobwhite quail chicks revealed a left-side turning bias in 85% of subjects.
      Such large population biases are considered unusual in nonhuman species.
      Experiments 1, 2, and 3 demonstrated that prenatal visual experience is a
      significant contributor to this population level left-side turning bias in
      bobwhite quail chicks. In contrast, prenatal auditory experience did not appear
      to significantly influence the development of postnatal turning bias. The
      findings of this study are discussed in terms of an epigenetic theory for the
      development of hemispheric specialization and behavioral asymmetry.

PMID- 9589222
TI  - A multivariate quantitative-genetic analysis of behavioral development in mice.
AB  - The present experiment attempted a behavior-genetic dissection of early
      behavioral development in laboratory mice. To this end, we used a full,
      replicated diallel cross to uncover the genetical architecture as well as the
      multivariate genetic structure underlying early behavioral ontogeny. A number of
      standard sensorimotor tests were administered on postnatal Days 3, 5, 8, 10, 13,
      17, and 22 to a total of 622 pups from 120 litters (4-6 pups per litter) from a
      four times replicated complete diallel cross between five inbred mouse strains.
      The first day on which an animal showed adult performance was taken as its score
      on that test. MANOVA did not show any effects of the pup's sex on the speed of
      development. Hayman's analysis of variance for diallel tables indicated no or
      only weak additive-genetic effects. Dominance was absent in almost all cases,
      except for the auricular startle response, where weak directional dominance for
      fast development was found. These results are in accordance with an evolutionary
      past of directional selection for well-canalized development. Factor analyses of
      the phenotypic and additive-genetic correlation matrices indicate that at least
      two factors are necessary to describe the behavioral variation.

PMID- 9589223
TI  - Classification of diabetic foot wounds.

PMID- 9589224
TI  - The effect of magnesium supplementation in increasing doses on the control of
      type 2 diabetes.
AB  - OBJECTIVE: Hypomagnesemia occurs in 25-38% of patients with type 2 diabetes.
      Several studies have suggested an association between magnesium (Mg) depletion
      and insulin resistance and/or reduction of insulin secretion in these cases. Our
      purpose was to evaluate if Mg supplementation (as magnesium oxide [MgO]) would
      improve metabolic control in patients with type 2 diabetes. RESEARCH DESIGN AND
      METHODS: We studied 128 patients with type 2 diabetes (32 men, 96 women, aged 30
      69 years), treated by diet or diet plus oral antidiabetic drugs, in the Bahia
      Federal University Hospital, Brazil. Patients at risk for hypomagnesemia or with
      reduced renal function were excluded. This study was a clinical randomized double
      blind placebo-controlled trial. Patients received either placebo, 20.7 mmol MgO,
      or 41.4 mmol MgO daily (elementary Mg) for 30 days. Mg concentrations were
      measured in plasma, in mononuclear cells, and in 24-h urine samples. Fasting
      blood glucose, HbA1, and fructosamine were used as parameters of metabolic
      control. RESULTS: Of the patients, 47.7% had low plasma Mg, and 31.1% had low
      intramononuclear Mg levels. Intracellular Mg in patients with diabetes was
      significantly lower than in the normal population (62 blood donors; 1.4 +/- 0.6
      vs. 1.7 +/- 0.6 micrograms/mg of total proteins). No correlation was found
      between plasma and intracellular Mg concentrations (r = -0.179; P = 0.15) or
      between Mg concentrations and glycemic control (r = -0.165; P = 0.12).
      Intracellular Mg levels were lower in patients with peripheral neuropathy than in
      those without (1.2 +/- 0.5 vs. 1.5 +/- 0.6 micrograms/mg). Similar findings were
      observed in patients with coronary disease (1.0 +/- 0.5 vs. 1.5 +/- 0.6
      micrograms/mg). In the placebo and in the 20.7 mmol Mg groups, neither a change
      in plasma and intracellular levels nor an improvement in glycemic control were
      observed. Replacement with 41.4 mmol Mg tended to increase plasma, cellular, and
      urine Mg and caused a significant fall (4.1 +/- 0.8 to 3.8 +/- 0.7 mmol/l) in
      fructosamine (normal, 1.87-2.87 mmol/l). CONCLUSIONS: Mg depletion is common in
      poorly controlled patients with type 2 diabetes, especially in those with
      neuropathy or coronary disease. More prolonged use of Mg in doses that are higher
      than usual is needed to establish its routine or selective administration in
      patients with type 2 diabetes to improve control or prevent chronic
      complications.

PMID- 9589225
TI  - The determinants of glycemic responses to diet restriction and weight loss in
      obesity and NIDDM.
AB  - OBJECTIVE: To examine the mechanisms by which weight loss improves glycemic
      control in overweight subjects with NIDDM, particularly the relationships between
      energy restriction, improvement in insulin sensitivity, and regional and overall
      adipose tissue loss. RESEARCH DESIGN AND METHODS: Hyperinsulinemic glucose clamps
      were performed in 20 subjects (BMI = 32.0 +/- 0.5 [SEM] kg/m2, age = 48.4 +/- 2.7
      years) with normal glucose tolerance (NGT) (n = 10) or mild NIDDM (n = 10) before
      and on the 4th (d4) and 28th (d28) days of a reduced-energy (1,100 +/- 250 [SD]
      kcal/day) formula diet. Body composition changes were assessed by dual energy x
      ray absorptiometry and insulin secretory changes were measured by insulin
      response to intravenous glucose before and after weight loss. RESULTS: In both
      groups, energy restriction (d4) reduced fasting plasma glucose (FPG) (delta FPG:
      NGT = -0.4 +/- 0.2 mmol/l and NIDDM = -1.1 +/- 0.03 mmol/l, P = 0.002), which was
      independently related to reduced carbohydrate intake (partial r = 0.64, P =
      0.003). There was a marked d4 increase in percent of insulin suppression of
      hepatic glucose output (HGO) in both groups (delta HGO suppression: NGT = 28 +/-
      15% and NIDDM = 32 +/- 8%, P = 0.002). By d28, with 6.3 +/- 0.4 kg weight loss,
      FPG was further reduced (d4 vs. d28) in NIDDM only (P = 0.05), and insulin
      sensitivity increased in both groups (P = 0.02). Only loss of abdominal fat
      related to improvements in FPG (r = 0.51, P = 0.03) and insulin sensitivity after
      weight loss (r = 0.48, P = 0.05). In contrast to insulin action, there were only
      small changes in insulin secretion. CONCLUSIONS: Both energy restriction and
      weight loss have beneficial effects on insulin action and glycemic control in
      obesity and mild NIDDM. The effect of energy restriction is related to changes in
      individual macronutrients, whereas weight loss effects relate to changes in
      abdominal fat.

PMID- 9589226
TI  - Beneficial effect on average lipid levels from energy restriction and fat loss in
      obese individuals with or without type 2 diabetes.
AB  - OBJECTIVE: The risk of cardiovascular disease in type 2 diabetes is greater than
      is accounted for by conventional risk factors. We investigated whether energy
      restriction or modest fat loss improved the lipid profile in obese subjects with
      and without type 2 diabetes. The relationship of site of adipose tissue loss to
      lipid changes was also examined. RESEARCH DESIGN AND METHODS: Lipid levels were
      measured in 18 subjects with normal glucose tolerance (NGT) (n = 9, BMI = 31.5 +/
      0.8 [SEM] kg/m2) or type 2 diabetes (n = 9, BMI = 31.8 +/- 0.7) before and on
      the 4th (d4) and 28th (d28) days of a hypocaloric formula diet. Body composition
      was assessed with dual energy X-ray absorptiometry on d0 and d28. RESULTS: Mean
      daily energy intake during the diet was 1,100 +/- 60 kcal (33% protein, 38%
      carbohydrate, and 29% fat). Mean weight loss was 6.2 +/- 0.4 kg. Initial lipid
      profiles were similar in subjects with or without diabetes, and diabetes did not
      affect the responses. Dietary intervention resulted in early (d4) and late (d28)
      changes. Energy restriction (d4) reduced VLDL cholesterol and total triglyceride
      (TG) concentrations and increased LDL particle size. LDL TG, and LDL
      apolipoprotein B (apoB) concentrations. Reduction in central abdominal fat (but
      not other body fat) was correlated with a less atherogenic lipid profile: delta
      abdominal fat versus delta LDL free cholesterol, r = 0.65, P = 0.006 and versus
      delta apoB, r = 0.64, P = 0.008. CONCLUSIONS: Even in obese subjects with an
      average lipid profile, modest weight loss reduces atherogenicity, independently
      of type 2 diabetes, and abdominal fat loss is specifically related to such
      improvements.

PMID- 9589227
TI  - The effects of metformin on glycemic control and serum lipids in insulin-treated
      NIDDM patients with suboptimal metabolic control.
AB  - OBJECTIVE: To test the hypothesis that metformin therapy, given as an adjunct to
      insulin therapy, improves metabolic control in insulin-treated NIDDM patients
      with suboptimal glycemic control. RESEARCH DESIGN AND METHODS: A total of 33
      subjects with insulin-treated NIDDM were investigated; all had commenced insulin
      after secondary failure of antihyperglycemic agents. Two randomized double-blind
      placebo-controlled crossover studies were run. In study 1 (n = 19), insulin
      treated subjects with suboptimal glycemic control received 12 weeks of metformin
      1 g b.i.d. and 12 weeks of placebo. In study 2 (n = 14), subjects already
      established on adjunctive metformin/insulin therapy stopped the metformin
      component and received 12 weeks of metformin at their baseline dosage (range 1
      2.5 g) and 12 weeks of equivalent placebo. Fasting plasma glucose, HbA1c, and
      serum lipids were measured at baseline and midway through and at the end of each
      treatment phase. The effect of 12 weeks of metformin treatment was compared with
      the effect of 12 weeks of placebo in each study and in both studies combined.
      RESULTS: In study 1, metformin treatment was associated with significant
      improvements in fasting plasma glucose (mean 12-week difference from placebo [95%
      CI]: 5.8 mmol/l [3.5-8.1], P < 0.001) and HbA1c (1.6% [0.9-2.4], P < 0.001). In
      study 2, metformin treatment was associated with significantly lower fasting
      plasma glucose (5.3 mmol/l [0.6-9.9], P = 0.029) and lower HbA1c (2.4% [1.0-3.8],
      P = 0.003) compared with those for placebo. Study 2 also showed metformin
      treatment to be associated with significantly lower total cholesterol than that
      for placebo (1.0 mmol/l [0.1-1.9], P = 0.032) and lower LDL cholesterol (1.0
      mmol/l [0.1-1.9], P = 0.028). This significant difference in serum lipids seen in
      study 2 was not seen in study 1, but was present when both sets of data were
      combined (n = 33, mean total cholesterol difference at 12 weeks [95% CI]: 0.6
      mmol/l [0.1-1.1], P = 0.015). Metformin had no significant effect on
      triglyceride, HDL cholesterol, weight, or blood pressure. Two subjects on
      metformin withdrew because of side effects. CONCLUSIONS: Metformin, when given as
      adjunctive therapy, was well tolerated and improved glycemic control and lipid
      concentrations in patients with insulin-treated NIDDM whose diabetes was poorly
      controlled. These improvements could be maintained over the long term.

PMID- 9589228
TI  - The reliability and validity of a brief diabetes knowledge test.
AB  - OBJECTIVE: To examine the reliability and validity of a brief diabetes knowledge
      test. The diabetes knowledge test has two components: a 14-item general test and
      a 9-item insulin-use subscale. RESEARCH DESIGN AND METHODS: Two populations
      completed the test. In one population, patients received diabetes care in their
      community from a variety of providers, while the other population received care
      from local health departments. Cronbach's coefficient alpha was used to calculate
      scale reliability for each sample. To determine validity, patient group
      differences were examined. It was hypothesized that test scores would be higher
      for patients with type 1 diabetes, for patients with more education, and for
      patients who had received diabetes education. RESULTS: The coefficient alpha s
      for the general test and the insulin-use subscale indicate that both are
      reliable, alpha > or = 0.70. In the community sample, patients with type 1
      diabetes scored higher than patients with type 2 diabetes on the general test and
      the insulin-use subscale. In the health department sample, patients with type 1
      scored higher than patients with type 2 on the insulin-use subscale. For both
      samples, scores increased as the years of formal education completed increased,
      and patients who received diabetes education scored higher than patients who did
      not. CONCLUSIONS: Although the samples differed demographically, the reliability
      and validity of the test were supported in both the community and the health
      department samples. This suggests that the test is appropriate for a variety of
      settings and patient populations.

PMID- 9589229
TI  - Effect of meal dilution on the postprandial glycemic response. Implications for
      glycemic testing.
AB  - OBJECTIVE: To investigate the effect of varying the volume of sugar meals on the
      post-prandial glycemic response (PGR). RESEARCH DESIGN AND METHODS: On six
      separate occasions, after an overnight fast, blood glucose concentrations were
      measured in eight healthy subjects (34 +/- 4 years of age, BMI 22.9 +/- 0.9
      kg/m2) after the consumption of 25 g glucose, sucrose, or fructose dissolved in
      either 200 or 600 ml of water. Blood was obtained at fasting and then at times
      15, 30, 45, 60, and 90 min after the start of the test meal. RESULTS: PGR was
      found to be influenced by carbohydrate type (P < 0.001). Mean response areas
      (min.mmol.l-1) to the three sugars were statistically different (P < 0.05).
      Glucose had the highest response area (90.0 +/- 8.1), followed by sucrose (61.3
      +/- 5.0) and then fructose (14.7 +/- 2.8). Independent of this effect, PGR was
      also found to be influenced by volume dose (P < 0.01). By tripling meal volume
      from 200 to 600 ml, PGR areas were significantly increased for all three sugars,
      glucose (79.3 +/- 10.3 vs. 100.8 +/- 12.0, P = 0.035), sucrose (52.6 +/- 5.5 vs.
      70 +/- 7.4, P = 0.0094), and fructose (11.0 +/- 3.8 vs. 18.4 +/- 3.9, P = 0.012).
      Where the effects of time (P < 0.05) and dose (P < 0.05) were determined to be
      independent (interaction nonsignificant) for all three sugars, this increase in
      volume also significantly increased glycemic concentrations at 15 min, for
      glucose (P = 0.033) and sucrose (P = 0.026), suggesting that changes in gastric
      emptying time may be a mechanism of action. CONCLUSIONS: Varying the volume of
      liquid sugar meals alters PGR. Understanding this concept may help to reduce
      variability both in the glycemic testing of foods and oral glucose tolerance
      testing.

PMID- 9589230
TI  - Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on
      glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men.
      Results of a controlled study.
AB  - OBJECTIVE: To evaluate the effect of a moderate dose of fish oil on glycemic
      control and in vivo insulin action in type 2 diabetic men with elevated plasma
      triacylglycerols and to determine the effect of the same treatment on gene
      expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL)
      in the abdominal adipose tissue. RESEARCH DESIGN AND METHODS: A total of 12 type
      2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish
      oil or sunflower oil, separated by a 2-month washout interval, in a double-blind
      crossover design. RESULTS: For glucose metabolism, 2 months of fish oil
      supplementation compared with sunflower oil led to similar fasting plasma
      insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase
      after fish oil. There was no difference in insulin suppression of hepatic glucose
      production nor in insulin stimulation of whole-body glucose disposal measured by
      the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA
      level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil
      lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to
      increase the amount of mRNA of both LPL and HSL in adipose tissue. CONCLUSIONS: A
      moderate dose of fish oil did not lead to deleterious effects on glycemic control
      or whole-body insulin sensitivity in type 2 diabetic men, with preserved
      triacylglycerol-lowering capacities.

PMID- 9589231
TI  - Development and application of a model to estimate the impact of type 1 diabetes
      on health-related quality of life.
AB  - OBJECTIVE: To develop a simulation model to assess the impact of type 1 diabetes
      and its associated complications on health-related quality of life of a
      population. RESEARCH DESIGN AND METHODS: The methodology builds upon 1) an
      existing population model of type 1 diabetes progression, 2) an empirical study
      designed to measure state- and age-specific health statuses of type 1 diabetes,
      and 3) existing literature to quantify quality of life of the corresponding
      health status. Health statuses were measured in a group of type 1 diabetic
      patients using the Medical Outcomes Study short form 36 (SF-36). A published
      empirical regression equation was then used to predict corresponding Quality of
      Well-Being Index (QWB) scores from these assessments. The QWB scores were
      incorporated into a previously developed type 1 diabetes progression and cost
      simulation model. Sensitivity analyses on key parameters were performed, and the
      model was found to be robust. RESULTS: The augmented model can estimate quality
      adjusted life years (QALYs) as well as costs associated with type 1 diabetes on
      any population of interest over any period of time. The model is used to compare
      intensive versus conventional treatment strategies using a simplified set of
      assumptions regarding the relative effects of these alternative treatments. With
      these assumptions, intensive strategy produces more QALYs than does conventional
      strategy and is cost-beneficial after 5 years. CONCLUSIONS: The model enables
      health planners to perform cost-effectiveness analyses to compare alternative
      treatment strategies for type 1 diabetes and support subsequent decision making.

PMID- 9589232
TI  - Prospective study of serum gamma-glutamyltransferase and risk of NIDDM.
AB  - OBJECTIVE: Serum gamma-glutamyltransferase (GGT) levels are raised in obese
      individuals, and a particularly strong association with central obesity has been
      described. We hypothesized that elevated GGT levels are a marker for visceral
      fat, and specifically for hepatic steatosis (fatty liver), and that hepatic
      steatosis leads to hepatic insulin resistance. To test this hypothesis, we
      examined the association between GGT levels and risk of NIDDM. RESEARCH DESIGN
      AND METHODS: We carried out a prospective cohort study of incident cases of
      doctor-diagnosed NIDDM in a group of 7,458 nondiabetic men (aged 40-59 years)
      followed for a mean of 12.8 years (range 11.5-13.0). The men were randomly
      selected from general practice lists in 24 British towns. Cases of NIDDM were
      ascertained by repeated postal questionnaires to the men and by regular
      systematic review of primary care records. RESULTS: A total of 194 men developed
      NIDDM during follow-up. Mean serum GGT at baseline (geometric mean [95% CI]) was
      significantly higher in the NIDDM patients than in the rest of the cohort (20.9
      [19.3-22.6] vs. 15.3 U/l [15.0-15.6], P < 0.0001). There was a smooth, graded
      increase in the age-adjusted risk of NIDDM with increasing GGT levels, with a
      relative risk in the top fifth of the distribution of 6.8 (3.5-12.9) relative to
      the bottom fifth (trend P < 0.0001). This association was independent of serum
      glucose and BMI and of other predictors of NIDDM with which GGT is associated,
      including alcohol intake and physical activity level (adjusted upper to lower
      fifth relative risk: 4.8 [2.0-11.8], trend P < 0.0001]). CONCLUSIONS: These
      findings suggest that a raised serum GGT level is an independent risk factor for
      NIDDM. Serum GGT level may be a simple and reliable marker of visceral and
      hepatic fat and, by inference, of hepatic insulin resistance.

PMID- 9589233
TI  - Diabetes and lower-limb amputations in the community. A retrospective cohort
      study. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside
      Scotland/Medicines Monitoring Unit.
AB  - OBJECTIVE: There are few U.K. data on the incidence rates of amputation in
      diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND
      METHODS: We performed a historical cohort study of first lower-extremity
      amputations based in Tayside, Scotland (population 364,880) from 1 January 1993
      to 31 December 1994. The Diabetes Audit and Research in Tayside Scotland (DARTS)
      database was used to identify a prevalence cohort of 7,079 diabetic patients on 1
      January 1993. We estimated age-specific and standardized incidence rates of lower
      limb amputations in the diabetic and nondiabetic cohorts. Results were compared
      with a previous study that evaluated lower-extremity amputations in diabetic
      patients in Tayside in 1980-1982. RESULTS: There were 221 subjects who underwent
      a total of 258 nontraumatic amputations. Of the 221 subjects, 60 (27%) patients
      were diabetic (93% NIDDM), and 63% were first amputations. The median duration of
      diabetes was 6 years (range: newly diagnosed to 41 years). Nonhealing ulceration
      (31%) and gangrene (29%) were the two main indications for amputation in the
      diabetic subjects. Of the 161 nondiabetic subjects, 140 (80%) underwent first
      amputations. The adjusted incidences in the diabetic and nondiabetic groups were
      248 and 20 per 100,000 person-years, respectively. Tayside patients with diabetes
      thus had a 12.3-fold risk of an amputation compared with nondiabetic residents
      (95% CI 8.6-17.5). The estimated proportion of diabetic patients in the
      population rose from 0.81% in 1980-1982 to 1.94% in 1993-1994, whereas the
      absolute rate of amputation in diabetic subjects was unchanged from that in 1980
      1982. CONCLUSIONS: These population-based U.K. amputation data are similar to
      amputation rates in the U.S. Amputation rates appear to have decreased
      significantly since 1980-1982. The impact of diabetes education and prevention
      programs that target the processes leading to amputation can now be evaluated.

PMID- 9589234
TI  - Incidence of IDDM in children living in Puerto Rico. Puerto Rican IDDM Coalition.
AB  - OBJECTIVE: To determine incidence, geographic distribution, and seasonal
      variation of IDDM in children 0-14 years of age living in Puerto Rico. Because
      these data have been collected through the infrastructure of the World Health
      Organization's DiaMond project, these results are directly comparable with
      incidence data from other population worldwide involved in this study. RESEARCH
      DESIGN AND METHODS: Beginning in 1990, new cases of IDDM were registered
      retrospectively from 1985 and prospectively to 1994 by review of medical records
      from island hospitals. Included in the hospital registry are 1,527 cases of IDDM.
      Validation of the primary source was by three secondary lists of cases obtained
      through diabetic camps, surveys of schools, and a government registry. Long
      linear modeling (capture-recapture) was used to correct incidence. RESULTS: Mean
      incidence of IDDM from 1985-1994 was 18.0 cases/100,000 children per year (95% CI
      17.6-18.3). There was a slight female rather than male predominance: 51% of the
      cases were girls, and 49% were boys. Although Puerto Rico has marked variation in
      rainfall, altitude, and genetic markers, no significant differences are found in
      the incidence rates of different areas or seasons of the island. CONCLUSIONS:
      This registry of Puerto Rican children is the largest IDDM registry of minority
      children in the U.S. The results of this study indicate that the annual incidence
      of IDDM of children living in Puerto Rico is higher than the incidence of other
      multiracial ethnic groups living in the U.S.

PMID- 9589235
TI  - Patterns of expenditures and use of services among older adults with diabetes.
      Implications for the transition to capitated managed care.
AB  - OBJECTIVE: To examine health care use and expenditures among older adults with
      diabetes, investigate factors that are associated with higher expenditures, and
      describe the policy implications of caring for this population under managed
      care. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of expenditures for
      individuals with diabetes over age 65 years from a nationwide 5% random sample of
      Medicare beneficiaries was conducted during 1992. All components of medical care
      covered under Medicare were examined. Multivariate analysis was used to assess
      the contribution of age, race, sex, number of diabetic complications, and
      comorbidity (Charlson Index) on total expenditures. RESULTS: On average,
      individuals with diabetes (n = 188,470) were 1.5 times (P < 0.0001) as expensive
      as all Medicare beneficiaries (n = 1,371,960). However, there were wide
      variations, with the most expensive 10% of beneficiaries with diabetes accounting
      for 56% of expenditures for individuals with diabetes and the least expensive 50%
      accounting for 4%. Acute care hospitalizations accounted for the majority (60%)
      of total expenditures, whereas outpatient and physician services accounted for 7
      and 33%, respectively. There were no differences in the number of complications
      for all older adults with diabetes compared with those with the highest
      expenditures. However, the average number of hospitalizations was 1.6 times (0.53
      vs. 0.34; P < 0.0001) higher, and the average length of stay was 2 days longer,
      among older adults with diabetes (P < 0.0001). In the regression model, age and
      male sex (factors currently used to set payment rates for Medicare managed care
      enrollees), and number of diabetic complications, but not race, were positively
      related to expenditures, yet had minimal predictive power (R2 = 0.0006). The
      addition of the Charlson Index, also positively related to expenditures, was able
      to explain up to 20% of the variation in total expenditures (R2 = 0.196).
      CONCLUSIONS: There are large variations in expenditures among older adults with
      diabetes. Because elderly beneficiaries with diabetes are more expensive than the
      average older adult, current Medicare capitation rates may be inadequate. To
      avoid selection bias and under-treatment of this vulnerable population under
      managed care, methods to construct fair payment rates and safeguard quality of
      care are desirable.

PMID- 9589236
TI  - Codon 972 polymorphism of the insulin receptor substrate-1 gene in impaired
      glucose tolerance and late-onset NIDDM.
AB  - OBJECTIVE: To assess the relevance of a Gly-->Arg substitution in codon 972 of
      the insulin receptor substrate-1 gene in impaired glucose tolerance (IGT) and
      NIDDM. RESEARCH DESIGN AND METHODS: The genotype of 1,106 Japanese subjects
      consisting of 310 subjects with NIDDM, 305 subjects with IGT, and 491 normal
      control subjects was analyzed by an allele-specific assay using polymerase chain
      reaction and restriction fragment length polymorphism. RESULTS: The frequency of
      the variant allele was not different between subjects with NIDDM (0.021) and
      normal control subjects (0.020). However, subjects with IGT showed a
      significantly higher prevalence of the variant allele (0.041, P = 0.027). We
      found two homozygous individuals for the variant; both had IGT with mild insulin
      resistance. The allelic frequency tended to be lower in normal control subjects
      aged > 50 years than in younger control subjects. Conversely, in the subjects
      with IGT or NIDDM, the Gly972Arg substitution was more frequently found in
      subjects aged > 50 years. Furthermore, NIDDM patients with the variant allele had
      older ages of diagnosis than patients without the variant. CONCLUSIONS: The codon
      972 variant may be associated with IGT and a subset of late-onset NIDDM in the
      elderly Japanese population.

PMID- 9589237
TI  - Validation of a diabetes-specific quality-of-life scale for patients with type 1
      diabetes.
AB  - OBJECTIVE: To validate a diabetes-specific quality-of-life scale and to assess
      its psychometric properties in a large sample of patients with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: To assess the quality of diabetes care in a
      population-based study, a representative sample of 684 patients with type 1
      diabetes was examined. A total of 657 patients (42% female; mean age 36 years;
      mean diabetes duration 18 years) completed the diabetes-specific quality-of-life
      scale (DSQOLS), which comprised 64 items on individual treatment goals (10
      items), satisfaction with treatment success (10 items), and diabetes-related
      distress (44 items). Statistical examinations covered factor analysis, internal
      consistency of subscales, and construct and discriminant validity. RESULTS:
      Factor analysis of the 44 items on diabetes-specific burdens revealed six
      reliable components (Cronbach's alpha): social relations (0.88), physical
      complaints (0.84), worries about future (0.84), leisure time flexibility (0.85),
      diet restrictions (0.71), and daily hassles (0.70). All six subscales were
      significantly correlated with a validated well-being scale (r = -0.35 to -0.53, P
      < 0.001) and treatment satisfaction (r = 0.28 to 0.43, P < 0.001). Physical
      complaints (r = 0.24) and worries about future (r = 0.17) showed the highest
      correlations with HbA1c (P < 0.001). A flexible insulin therapy, a liberalized
      diet, the absence of late complications, and a higher social status were
      significantly associated with more favorable scores in different domains.
      CONCLUSIONS: The DSQOLS is a reliable and valid measure of diabetes-specific
      quality of life. The scale is able to distinguish between patients with different
      treatment and dietary regimens and to detect social inequities. Use of the DSQOLS
      for assessment of individual treatment goals as defined by the patients may be
      helpful to identify motivational deficits and to tailor individual treatment
      strategies.

PMID- 9589238
TI  - Adaptation of the Dartmouth COOP Charts for use among American Indian people with
      diabetes.
AB  - OBJECTIVE: To adapt the Dartmouth COOP Charts for use among American Indians with
      diabetes and to evaluate the operating characteristics of the adapted charts
      because measures of health status have not been evaluated for use among American
      Indians with diabetes. RESEARCH DESIGN AND METHODS: American Indian adults
      participated in focus group conferences to adapt and review the Dartmouth COOP
      Charts for use in American Indian communities. American Indian participants with
      diabetes were interviewed and administered the adapted charts. The operating
      characteristics of the charts were evaluated by measuring internal and external
      consistency, reliability, and acceptability. RESULTS: Some of the wording and
      pictures were considered to be offensive and culturally inappropriate in American
      Indian communities. The adapted charts showed internal consistency in a
      comparison of interchart variables. CONCLUSIONS: The adapted Dartmouth COOP
      Charts are more culturally acceptable than the original charts and appear to
      measure constructs adequately.

PMID- 9589239
TI  - Use of the therapeutic footwear benefit among diabetic medicare beneficiaries in
      three states, 1995.
AB  - OBJECTIVE: To determine the extent to which Medicare provided reimbursement for
      therapeutic footwear to diabetic Medicare beneficiaries in Washington, Alaska,
      and Idaho in 1995. RESEARCH DESIGN AND METHODS: Using inpatient, outpatient, and
      durable medical equipment claims data, we selected a cohort of diabetic Medicare
      beneficiaries. Therapeutic footwear claims were identified using a set of billing
      codes intended only for the diabetes footwear benefit. People at "high risk" or
      "possibly increased risk" for foot problems who might benefit from therapeutic
      footwear were identified using a combination of International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes in
      any of the databases. RESULTS: Among 608,804 beneficiaries, 10.2% (62,170) met
      the inclusion criteria for diabetes. Of the diabetic beneficiaries, 13.0% (8,079)
      had at least one "high risk" diagnosis, and 14.0% (8,686) had at least one
      "possibly increased risk" diagnosis. The percentage of diabetic beneficiaries
      with therapeutic footwear claims was 2.9% among those with diagnoses high risk,
      0.7% among those with diagnoses indicating possibly increased risk, and 0.1%
      among those with no diagnosis from the list. Altogether, only 0.6% of
      beneficiaries meeting the diabetes case ascertainment criteria had a therapeutic
      footwear claim in 1995. CONCLUSIONS: Few diabetic Medicare beneficiaries in
      Washington, Alaska, and Idaho had claims for reimbursement for therapeutic
      footwear in 1995. The low utilization of the footwear benefit may represent an
      important opportunity to improve care for Medicare beneficiaries with diabetes.
      Further work should be done to characterize the use of the benefit in other
      regions and to assess whether the low level of usage reflects underutilization.

PMID- 9589240
TI  - Leptinemia is not a risk factor for ischemic heart disease in men. Prospective
      results from the Quebec Cardiovascular Study.
AB  - OBJECTIVE: To investigate the possibility that leptin levels may be predictive of
      the risk of ischemic heart disease (IHD) through the relationship of leptin to
      body fat. RESEARCH DESIGN AND METHODS: The Quebec Cardiovascular Study cohort
      consisted of 2,103 French-Canadian men without IHD in 1985 who were followed
      until 1990, by which time 114 had experienced an IHD event. These 114 men were
      then individually matched for age, BMI, cigarette smoking, and alcohol intake
      with 114 subjects who were free of IHD at follow-up. After exclusion of diabetic
      patients and those in whom leptin levels could not be measured, we were able to
      compare the initial metabolic profiles of 86 men in the IHD group and of 95
      control subjects. RESULTS: Plasma leptin concentrations were positively
      correlated with BMI (r = 0.67, P < 0.0001) and with fasting insulin
      concentrations (r = 0.46, P < 0.0001) in the overall sample. These significant
      associations were also observed when men with IHD and the control subjects were
      examined separately (control subjects: r = 0.68 for BMI and r = 0.45 for insulin;
      IHD subjects: r = 0.65 for BMI and r = 0.50 for insulin). With the exception of
      plasma triglyceride (r = 0.25, P < 0.001), no significant association was found
      between leptin and plasma lipoprotein and lipid concentrations. Furthermore,
      plasma insulin remained significantly associated with leptin levels even after
      adjustment for BMI (r = 0.22, P < 0.005). There was no difference in baseline
      leptin levels among men who developed IHD versus men who remained IHD-free during
      the 5-year follow-up (5.56 +/- 3.12 vs. 5.36 +/- 2.90 ng/ml, respectively). Thus,
      although significantly correlated with the BMI and fasting insulin levels, plasma
      leptin concentration was not a significant predictor of the 5-year incidence of
      IHD. This lack of a relationship to IHD was noted when leptin levels were
      analyzed as tertiles and when leptin concentration was analyzed as a continuous
      variable. CONCLUSIONS: These prospective results suggest that leptinemia, despite
      being a strong correlate of obesity, does not appear to be an independent risk
      factor for the development of IHD in men.

PMID- 9589241
TI  - Objective assessment of smoking habits by urinary cotinine measurement in
      adolescents and young adults with type 1 diabetes. Reliability of reported
      cigarette consumption and relationship to urinary albumin excretion.
AB  - OBJECTIVE: To examine the relationship of objective smoking status to age, sex,
      longterm metabolic control, and urinary albumin excretion. Patients with type 1
      diabetes who smoke are at increased risk to develop diabetic microvascular and
      macrovascular complications. While this has repeatedly been demonstrated in
      adults, smoking habits have rarely been investigated in adolescents. RESEARCH
      DESIGN AND METHODS: Urinary continine excretion has been determined by
      radioimmunoassay in 238 adolescents and young adults with type 1 diabetes. This
      biochemical parameter of nicotine use was related to age, to the number of
      cigarettes allegedly consumed per day, and to urinary albumin excretion. RESULTS:
      A total of 46 patients (19.3%) with urinary cotinine values > 500 ng/ml were
      classified as smokers. In 26 patients (10.9%), cotinine values between 100 and
      500 ng/ml were found (infrequent smokers or environmental nicotine exposure),
      while the remaining 166 patients excreted < 100 ng/ml of cotinine in the urine
      (nonsmokers). Smokers were significantly older (20.2 +/- 0.6 years [mean +/- SE])
      compared with the intermediate group (18.3 +/- 0.7 years) or with nonsmokers
      (15.9 +/- 0.4 years; P < 0.0001, Wilcoxon's signed-rank test). Of 46 smokers, 12
      denied smoking cigarettes entirely, and among biochemically defined smokers, no
      correlation was present between urinary continine excretion and the reported
      number of cigarettes consumed per day. Urinary albumin excretion was
      significantly higher in smokers compared with nonsmokers (P < 0.003).
      CONCLUSIONS: These data demonstrate that cigarette smoking is common among German
      adolescents and young adults with type 1 diabetes in this study. Many patients
      deny nicotine use or refuse to disclose their smoking habits. Increased urinary
      albumin excretion is consistent with an increased risk of nephropathy in subjects
      with diabetes who smoke. Pediatricians in charge of adolescents with type 1
      diabetes should actively discuss the risk of nicotine consumption with their
      patients.

PMID- 9589242
TI  - Development of proliferative diabetic retinopathy in African-Americans and whites
      with type 1 diabetes.
AB  - OBJECTIVE: To investigate the comparable risk of developing proliferative
      diabetic retinopathy (PDR) in African-Americans and whites with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: Using a cohort design with the sample drawn from
      medical records, the sample consisted of 312 people with type 1 diabetes (97
      African-Americans, 215 whites) having at least two visits to a Model
      Demonstration Unit with gradeable fundus photographs (stereo, color, 7 standard
      fields). Excluded were subjects with preexisting or treated PDR or
      hemoglobinopathy. Masked grading of the fundus photographs was conducted at the
      Wisconsin Reading Center. RESULTS: At baseline, African-Americans had poorer
      glycemic control (mean HbA1 of 11.3 vs. 10.0%, P < 0.0001), higher systolic blood
      pressure (mean of 117 vs. 110 mmHg, P < 0.001), and were older (mean of 26.8 vs.
      19.3 years, P < 0.0001) than the white subjects. African-Americans also tended to
      have slightly longer duration of diabetes and length of follow-up. In the African
      Americans, 17.5% developed PDR, compared with 10.2% in the 215 whites, for an
      odds ratio (OR) of 1.86 (95% CI 0.93-3.70). When adjusted for baseline glycemic
      control, retinopathy grade, and length of follow-up, race was not a significant
      risk factor (OR = 0.73, 95% CI 0.30-1.78). CONCLUSIONS: African-Americans with
      type 1 diabetes may have a higher rate of developing PDR. The observed racial
      difference, however, is attributable to the presence of a worse risk factor
      profile, especially to poorer glycemic control. Efforts should be expanded to
      improve the care for all individuals with poor glycemic control.

PMID- 9589243
TI  - Troglitazone decreases the proportion of small, dense LDL and increases the
      resistance of LDL to oxidation in obese subjects.
AB  - OBJECTIVE: Insulin resistance is associated with a predominance of small,
      atherogenic LDL particles that are more prone to oxidative modification.
      Treatment with the insulin-sensitizer troglitazone may improve LDL composition
      and resistance to oxidation. RESEARCH DESIGN AND METHODS: In a randomized double
      blind crossover design, 15 obese subjects were treated with either 400 mg
      troglitazone daily or placebo for 8 weeks. Insulin sensitivity (clamp),
      (apo)lipoproteins, LDL subclass pattern, plasma TBARS, and ex vivo LDL oxidation
      were determined. RESULTS: Troglitazone treatment improved insulin sensitivity.
      LDL cholesterol increased from 2.58 +/- 0.18 to 2.77 +/- 0.20 mmol/l (P = 0.03)
      because of an increase in large (buoyant) LDL1 (from 0.45 +/- 0.04 to 0.62 +/-
      0.09 mmol/l, P = 0.008). Because small (dense) LDL3 decreased, LDL1:LDL3 ratio
      increased (P = 0.02). Plasma TBARS concentration declined significantly, and the
      lag time of ex vivo LDL oxidation showed a small but significant increase.
      CONCLUSIONS: In obese subjects, treatment with troglitazone improves insulin
      sensitivity, increases the ratio of large buoyant to small dense LDL, and appears
      to enhance the resistance of the LDL particle to oxidation. These qualitative
      changes in lipoproteins may have a beneficial effect on cardiovascular risk
      profile and compensate for a small increase in LDL cholesterol.

PMID- 9589244
TI  - Time-action profiles of novel premixed preparations of insulin lispro and NPL
      insulin.
AB  - OBJECTIVE: To study the pharmacodynamic properties of three premixed formulations
      of the rapid-acting insulin analog insulin lispro and its protamine-retarded
      preparation, neutral protamine lispro (NPL) insulin. RESEARCH DESIGN AND METHODS:
      In this open, single-center, euglycemic glucose clamp study, 30 healthy
      volunteers (12 women, 18 men) aged 27 +/- 2 years (mean +/- SD), whose BMI was
      23.0 +/- 2.3 kg/m2, received subcutaneous injections of 0.3 U/kg body wt of
      insulin mixture (high-mixture 75/25, mid-mixture 50/50, or low-mixture 25/75
      insulin lispro/NPL insulin), insulin lispro, or NPL insulin on one of the five
      study days in randomized order. Glucose infusion rates were determined over a
      period of 24 h after administration. RESULTS: Maximal metabolic activity
      decreased after subcutaneous injection of the mixtures with lower insulin lispro
      content; however, the time point of maximal and of early half-maximal metabolic
      activity was comparable among the three mixtures. Higher proportions of insulin
      lispro resulted in higher values for area under the curve within the first 360
      min after injection and a more rapid decline to late half-maximal activity. Serum
      insulin concentrations showed a similar pattern. CONCLUSIONS: This study shows
      that the pharmacodynamic and pharmacokinetic properties of insulin lispro are
      preserved in stable mixtures with NPL insulin.

PMID- 9589245
TI  - Beneficial impact of ramipril on left ventricular hypertrophy in normotensive
      nonalbuminuric NIDDM patients.
AB  - OBJECTIVE: To evaluate the effect of the ACE inhibitor ramipril as compared with
      placebo on left ventricular mass index (LVMI) in normotensive, nonalbuminuric
      NIDDM patients with left ventricular hypertrophy (LVH). Patients with NIDDM are
      characterized by excessive cardiovascular morbidity and mortality, and LVH, an
      independent risk factor for cardiac events, is often present in NIDDM patients.
      RESEARCH DESIGN AND METHODS: A total of 38 normotensive, nonalbuminuric
      (albuminuria < 100 mg/24 h) NIDDM patients with LVH (LVMI > 131 g/m2 in men and >
      100 g/m2 in women) were enrolled in a 6-month randomized, double-blind parallel
      group study to compare the effects of ramipril (5 mg/day) with placebo on LVMI
      (echocardiography, Vingmed CFM725, Diasonics Sonotron), QTc dispersion determined
      as the interlead variation in QTc interval on standard electrocardiogram (ECG),
      and 24-h ambulatory blood pressure (A&D TM2420, Tokyo, Japan). A total of 16
      ramipril (10 men, 60 +/- 9 years [mean +/- SD]) and 15 placebo-treated (8 men, 55
      +/- 10 years) patients completed the study, and their data are presented.
      RESULTS: Ambulatory blood pressure was almost identical at baseline (132/76 +/-
      3/1 vs. 133/74 +/- 5/2 mmHg [mean +/- SEM]) and remained stable during follow-up
      (134/76 +/- 3/1 vs. 136/74 +/- 6/2 mmHg) in the ramipril and placebo group,
      respectively. LVMI was comparable at baseline (137.1 +/- 7.0 vs. 129.6 +/- 3.7
      g/m2) in the ramipril and placebo group, respectively, and decreased
      significantly more in the ramipril group as compared with the placebo group (17.6
      +/- 3.0 vs. 5.7 +/- 4.6 g/m2, respectively, 11.9 [0.7-23.1] g/m2, mean difference
      [95% CI]; P = 0.037). QTc dispersion was comparable at baseline (60.2 [5.5] vs.
      64.1 [6.5] ms) and did not change significantly during follow-up: -2.5 [7.0] vs. 
      12.2 [9.5] ms; mean difference 9.8 (-14.2 to 33.8 ms) in the ramipril and placebo
      group, respectively. CONCLUSIONS: Ramipril induces regression of LVH in
      normotensive, nonalbuminuric NIDDM patients, independent of reduction in systemic
      blood pressure.

PMID- 9589246
TI  - Changes in amylin and amylin-like peptide concentrations and beta-cell function
      in response to sulfonylurea or insulin therapy in NIDDM.
AB  - OBJECTIVE: Amylin, a secretory peptide of beta-cells, is the constituent peptide
      of islet amyloid, which is characteristic of NIDDM, and changes in amylin
      secretion in response to therapies may influence the rate of production of islet
      amyloid. The primary objective of this study was to determine whether therapy
      with sulfonylurea or basal insulin in NIDDM would alter amylin secretion in a way
      that might affect the formation of islet amyloid. RESEARCH DESIGN AND METHODS: In
      a randomized crossover design, eight subjects with NIDDM underwent three 8-week
      periods of therapy with diet alone, sulfonylurea, or exogenous basal insulin,
      with evaluation of amylin, amylin-like peptide (ALP), and glucose and C-peptide
      concentrations, both during fasting and after a standard breakfast. Changes in
      beta-cell function (% beta) were assessed, in the basal state by homeostasis
      model assessment (HOMA) and in the stimulated state by hyperglycemic clamps.
      Seven nondiabetic control subjects each underwent a meal profile and
      hyperglycemic clamp. RESULTS: Both sulfonylurea and insulin therapy reduced basal
      glucose concentrations compared with diet alone, but neither reduced the
      increased postprandial glucose increments. Both sulfonylurea and insulin therapy
      increased basal % beta, assessed by HOMA, but only sulfonylurea increased the
      second-phase C-peptide responses to the hyperglycemic clamp. Sulfonylurea
      increased time-averaged mean postprandial amylin and ALP concentrations compared
      with diet alone (geometric mean [1-SD range] for amylin, 4.9 [2.0-11.8] vs. 3.0
      [1.4-6.2] pmol/l, P = 0.003; for ALP, 16.4 [8.5-31.7] vs. 10.1 [4.9-20.8] pmol/l,
      P = 0.001). Insulin therapy reduced basal ALP concentrations compared with diet
      alone (2.9 [1.5-5.6] vs. 6.0 [2.6-13.6] pmol/l, P = 0.03), but had no effect on
      postprandial concentrations of amylin (3.0 [1.3-6.5] pmol/l) or ALP (10.0 [5.5
      18.1] pmol/l). CONCLUSIONS: By increasing postprandial concentrations of the
      constituent peptides of islet amyloid, sulfonylurea therapy might increase the
      rate of deposition of islet amyloid and thereby accelerate the decline of % beta
      in NIDDM, compared with diet therapy alone.

PMID- 9589247
TI  - Comparison of human regular and lispro insulins after interruption of continuous
      subcutaneous insulin infusion and in the treatment of acutely decompensated IDDM.
AB  - OBJECTIVE: To compare the rapidity of metabolic decompensation after interruption
      of CSII between human regular and lispro insulin and to compare these two
      insulins in the correction of the hyperglycemia and ketosis of mildly
      decompensated IDDM. Lispro insulin may be especially useful for insulin pump
      therapy (continuous subcutaneous insulin infusion [CSII]). RESEARCH DESIGN AND
      METHODS: A total of 18 patients with well-controlled IDDM (HbA1c 7.7 +/- 1.1%,
      age 30 +/- 11 years) were studied. All were being treated with CSII (nine with
      human regular and nine with lispro insulin). The study consisted of two phases:
      1) an insulin interruption phase, in which the basal insulin infusion was stopped
      (at 0300) and plasma insulin, glucose, and beta-O-hydroxybutyrate (beta-OHB) were
      measured every 15-60 min for 6 h after interruption of the insulin infusion and
      2) an insulin replacement phase, which involved measuring plasma insulin,
      glucose, and beta-OHB for 2 h after a single injection of either human regular or
      lispro insulin to correct the hyperglycemia and ketosis that developed during the
      first phase of the study. RESULTS: After interruption of the basal insulin
      infusion during the insulin interruption phase, plasma insulin levels fell
      gradually in both groups to nadir values of 1.6 +/- 0.8 and 2.0 +/- 1.2 microU/ml
      in the regular insulin- and insulin lispro-treated groups, respectively. Plasma
      glucose concentrations rose to 13.8 +/- 1.9 and 16.0 +/- 1.7 mmol/l in the
      regular insulin- and insulin lispro-treated groups, respectively. No significant
      differences were seen between the therapy groups at any time in the insulin
      levels or in the concentrations of plasma glucose or beta-OHB. In the insulin
      replacement phase, insulin levels rose more rapidly in those treated with lispro
      insulin, reaching a greater peak value (e.g., at 60 min, plasma insulin 25 +/-
      3.4 vs. 15.6 +/- 2.6 microU/ml, P < 0.05). In association with this, plasma
      glucose decreased to a lower nadir after lispro insulin (9.7 +/- 0.4 vs. 13.7 +/-
      0.7 mmol/l, lispro- vs. regular-treated groups at 120 min after insulin
      administration, P < 0.01). beta-OHB levels decreased rapidly in both groups.
      CONCLUSIONS: In patients treated with CSII, interruption of the basal insulin
      infusion in the middle of the night does not result in more rapid metabolic
      decompensation in patients treated with lispro compared with those treated with
      regular human insulin. Lispro insulin is effective in treating mild ketosis and
      hyperglycemia, and its rapid action may be advantageous in the "sick day"
      management at home of patients with IDDM.

PMID- 9589248
TI  - Efficacy and safety of a topical gel formulation of recombinant human platelet
      derived growth factor-BB (becaplermin) in patients with chronic neuropathic
      diabetic ulcers. A phase III randomized placebo-controlled double-blind study.
AB  - OBJECTIVE: To compare the efficacy and safety of topically applied recombinant
      human platelet-derived growth factor-BB (rhPDGF-BB) (becaplermin) with placebo
      gel in patients with chronic diabetic neuropathic ulcers of the lower
      extremities. RESEARCH DESIGN AND METHODS: This multicenter double-blind placebo
      controlled phase III trial included 382 patients with type 1 or type 2 diabetes
      and chronic ulcers of at least 8 weeks' duration. After sharp debridement of the
      ulcer, patients were randomized to receive becaplermin gel 30 micrograms/g,
      becaplermin gel 100 micrograms/g, or placebo gel, in conjunction with a
      standardized regimen of good wound care until complete wound closure was achieved
      or for a maximum of 20 weeks. Moist saline-soaked gauze dressings were changed
      twice daily with study medication applied by patients or caregivers at the
      evening dressing change. Safety was assessed by monitoring adverse events (AEs)
      and by clinical laboratory evaluations. RESULTS: Compared with placebo gel,
      becaplermin gel 100 micrograms/g significantly increased the incidence of
      complete wound closure by 43% (50 vs. 35%, P = 0.007) and decreased the time to
      achieve complete wound closure by 32% (86 vs. 127 days; estimated 35th
      percentile, P = 0.013). AEs reported during treatment or during a 3-month follow
      up period were similar in nature and incidence across all treatment groups.
      CONCLUSIONS: Becaplermin gel 100 micrograms/g, in conjunction with good wound
      care, significantly increased the incidence of complete wound closure and
      significantly reduced the time to complete closure of chronic diabetic
      neuropathic ulcers. The safety profile of becaplermin gel was similar to that of
      placebo gel.

PMID- 9589249
TI  - Do postmenopausal women with NIDDM have a reduced capacity to deposit and
      conserve lower-body fat?
AB  - OBJECTIVE: To compare regional body fat distribution and sex hormone status of
      postmenopausal women with NIDDM with those of age- and BMI-matched normoglycemic
      women. RESEARCH DESIGN AND METHODS: The regional body fat distribution and sex
      hormone status of 42 postmenopausal women with NIDDM were compared with those of
      42 normoglycemic women matched for age and BMI, who served as control subjects.
      Body composition was measured by dual-energy X-ray absorptiometry, and sex
      hormone-binding globulin (SHBG) and testosterone were measured in serum. RESULTS:
      Although the levels of total body fat were similar between the two groups, the
      women with NIDDM had significantly less lower-body fat (LBF) (P < 0.01) than the
      control subjects matched for age and BMI. This pattern of fat deposition in women
      with NIDDM was accompanied by an androgenic hormone profile, with decreased SHBG
      concentration and an increased free androgen index (P < 0.05 and P < 0.01,
      respectively). CONCLUSIONS: A reduced capacity to deposit and/or conserve LBF may
      be an independent factor associated with (or may be a marker of) the metabolic
      manifestations of the insulin resistance syndrome in women with NIDDM. The
      possibility that the smaller relative accumulation of LBF is a consequence of the
      androgenic hormonal profile should be investigated in future studies.

PMID- 9589250
TI  - Pubertal growth in IDDM is determined by HbA1c levels, sex, and bone age.
AB  - OBJECTIVE: In cross-sectional studies of subjects with IDDM, the relationship
      between suboptimal pubertal growth, glycemic control, and abnormal insulin-like
      growth factor I (IGF-I) levels has proved difficult to define. The objective of
      this study was to examine these relationships in a longitudinal prospective
      study. RESEARCH DESIGN AND METHODS: A total of 46 children (23 boys) were
      measured every 3 months, and their bone age was assessed annually. Blood samples
      were obtained for HbA1c, IGF-I, and C-peptide. Growth data were compared with
      national standards, and IGF-I data were compared with a parallel longitudinal
      study of normal schoolchildren. Data were analyzed as SD scores (mean +/- SD).
      RESULTS: The onset of puberty was not delayed, although in the girls, bone age
      was advanced (bone age, 11.48 +/- 1.01 years vs. chronological age, 10.93 +/-
      0.86 years [mean +/- SD]; P = 0.04). The timing of peak height velocity (PHV) was
      normal in both sexes, but the magnitude was reduced in girls (PHV SDS = -0.56 +/-
      0.90, P < 0.02), and reductions in height SDS between diagnosis and final height
      were observed (P = 0.014). At PHV, IGF-I levels were reduced in both sexes, and
      there were no sex differences in HbA1c levels and insulin doses. IGF-I SDS
      correlated with insulin dose (r = 0.47, P = 0.004) but not with PHV SDS, whereas
      HbA1c correlated negatively with PHV SDS in both sexes (r = -0.35, P = 0.03). In
      a stepwise multiple regression analysis, the major determinants of PHV SDS were
      HbA1c (P = 0.04), sex (P = 0.0007), and bone age (P = 0.01). CONCLUSIONS: We
      conclude that the magnitude of the pubertal growth spurt is related to HbA1c
      levels in both sexes, but it is reduced only in girls. This sexual dimorphism
      cannot be explained by differences in IGF-I levels and may relate to the bone age
      advance at the onset of puberty in the girls.

PMID- 9589251
TI  - Evaluation of the insertion/deletion ACE gene polymorphism as a risk factor for
      carotid artery intima-media thickening and hypertension in young type 1 diabetic
      patients.
AB  - OBJECTIVE: To study the distribution of the insertion/deletion polymorphism of
      the ACE gene in young type 1 diabetic patients and to evaluate possible
      associations between the ACE genotype, arterial hypertension, and intima-media
      thickness (IMT) of the common carotid artery. RESEARCH DESIGN AND METHODS: Study
      participants were 148 type 1 diabetic patients (56 men and 92 women), aged 14-44
      years, with a diabetes duration of > or = 2 years. HbA1c, albuminuria, and lipid
      status were assessed by standard laboratory techniques; the ACE genotypes were
      assessed by polymerase chain reaction. The patients were categorized according to
      the presence or absence of hypertension, nephropathy, and retinopathy. The IMT,
      which can be used to estimate early stages of atherosclerosis, was measured by
      high-resolution ultrasonography. RESULTS: The ACE genotypes were distributed as
      follows: 21% II, 37% ID, 42% DD. The IMT values did not differ among patients
      with various ACE genotypes (0.63 +/- 0.15 mm), but the prevalence of hypertension
      was significantly higher in patients with DD (odds ratio, 4.26 versus II + ID;
      95% CI, 1.64-11.06). Multiple linear regression analysis showed that only age,
      hypertension, and sex were determinants for the IMT. CONCLUSIONS: Our results
      suggest a relationship between the prevalence of hypertension and the deletion
      polymorphism of the ACE gene in young type 1 diabetic patients, but we could not
      find an association between carotid artery IMT and ACE genotype in this
      population.

PMID- 9589253
TI  - Variants of the fatty acid-binding protein 2 gene are not associated with
      coronary heart disease in nondiabetic subjects and in patients with NIDDM.
AB  - OBJECTIVE: To investigate the association of variants of the fatty acid-binding
      protein (FABP) 2 gene with coronary heart disease (CHD) in nondiabetic subjects
      and in patients with NIDDM. RESEARCH DESIGN AND METHODS: Cross-sectional study
      included 135 nondiabetic and 79 NIDDM subjects with stenosis (> 50%) in at least
      two coronary arteries. A group of 81 healthy nondiabetic men without CHD served
      as a control population. All exons and intron-exon junctions of the FABP2 gene
      were amplified with the polymerase chain reaction, and variants were screened
      with the single-strand conformation polymorphism analysis. RESULTS: The allele
      frequency of an amino acid polymorphism (alanine-->threonine) in codon 54 of exon
      2 of the FABP2 gene was 0.26 in nondiabetic subjects with CHD and 0.27 in NIDDM
      subjects with CHD. Other variants (GTA 118 GTC, GCGCA-->GCACA in the 3'-noncoding
      region, and the number of ATT repeats in intron 2) also did not associate with
      CHD. CONCLUSIONS: The variants of the FABP2 gene are not likely to contribute to
      the risk of CHD in Finnish nondiabetic and NIDDM subjects.

PMID- 9589252
TI  - Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM.
AB  - OBJECTIVE: Considering that elevated blood levels of homocyst(e)ine represent a
      known independent risk factor for macrovascular disease, we assessed the link
      between hyperhomocyst(e)inemia and diabetic microvascular complications. RESEARCH
      DESIGN AND METHODS: Homocyst(e)ine and thrombomodulin plasma levels, a marker of
      endothelial cell damage, were measured before and 3 h after oral methionine
      loading in 75 patients with stable, well-controlled IDDM and 40 healthy control
      subjects matched for sex and age. Exclusion criteria were hyperlipidemia,
      hypertension, smoking, or positive family history for cardiovascular disease.
      RESULTS: IDDM patients had higher pre- and postload homocyst(e)ine plasma levels
      than did healthy control subjects (12.0 vs. 7.7 mumol/l and 27.6 vs. 16.0
      mumol/l; P < 0.001). Of 75 IDDM patients, 26 had homocyst(e)ine plasma levels
      above the normal range (defined as mean +2 SD of values obtained in the control
      group). The IDDM patients with hyperhomocyst(e)inemia had higher thrombomodulin
      plasma levels (62.2 vs. 38.2 ng/ml; P < 0.001), higher albumin excretion rates
      (485 vs. 115 mg/l; P < 0.005), and a higher prevalence of late diabetic
      complications (nephropathy, 76 vs. 33%; retinopathy, 69 vs. 51%; neuropathy, 57
      vs. 41%; macroangiopathy, 57 vs. 33%) compared with IDDM patients with normal
      plasma homocyst(e)ine. In vitro experiments with human umbilical vein cells show
      an increased release of thrombomodulin into the culture supernatant only when
      endothelial cells were pretreated with advanced glycation end product (AGE)
      albumin before L-homocystine was added. A synergistic action of homocyst(e)ine
      and AGEs might contribute to vascular complications of patients with diabetes.
      CONCLUSIONS: Hyperhomocyst(e)inemia is common in nephropathic diabetic patients
      and may contribute to the enhanced morbidity and mortality from cardiovascular
      diseases characteristically observed in IDDM patients with diabetic nephropathy.

PMID- 9589254
TI  - Absence of association between genetic variation of the beta 3-adrenergic
      receptor and metabolic phenotypes in Oji-Cree.
AB  - OBJECTIVE: To assess the association between the common missense variant, Y64R,
      in the gene encoding the beta 3-adrenergic receptor, ADRB3, and intermediate
      phenotypes related to obesity and NIDDM in Canadian Oji-Cree. RESEARCH DESIGN AND
      METHODS: We determined genotypes of the ADRB3 Y64R polymorphism in 508 clinically
      and biochemically well-characterized adult Oji-Cree, of whom 115 had NIDDM. We
      tested for associations with multivariate analysis of variance. RESULTS: We found
      the ADRB3 R64 allele frequency to be 0.40 in this population, which is the
      highest yet observed in a human population. Furthermore, 15% of subjects were
      R64/R64 homozygotes, compared with a virtual absence of homozygotes in European
      study samples. However, we found no statistically significant associations of the
      ADRB3 Y64R genotype either with the presence of NIDDM, with indexes of obesity,
      or with intermediate quantitative biochemical traits related to NIDDM.
      CONCLUSIONS: Despite the very high frequency of the ADRB3 R64 allele in this
      sample of aboriginal people, it was not associated with any metabolic phenotype.
      This suggests that the ADRB3 R64 allele is probably not a major determinant of
      obesity or NIDDM in these aboriginal Canadians.

PMID- 9589255
TI  - Validation of a diabetic wound classification system. The contribution of depth,
      infection, and ischemia to risk of amputation.
AB  - OBJECTIVE: To validate a wound classification instrument that includes assessment
      of depth, infection, and ischemia based on the eventual outcome of the wound.
      RESEARCH DESIGN AND METHODS: We evaluated the medical records of 360 diabetic
      patients presenting for care of foot wounds at a multidisciplinary tertiary care
      foot clinic. As per protocol, all patients had a standardized evaluation to
      assess wound depth, sensory neuropathy, vascular insufficiency, and infection.
      Patients were assessed at 6 months after their initial evaluation to see whether
      an amputation had been performed. RESULTS: There was a significant overall trend
      toward increased prevalence of amputations as wounds increased in both depth (chi
      2trend = 143.1, P < 0.001) and stage (chi 2trend = 91.0, P < 0.001). This was
      true for every subcategory as well with the exception of noninfected, nonischemic
      ulcers. There were no amputations performed within this stage during the follow
      up period. Patients were more than 11 times more likely to receive a midfoot or
      higher level amputation if their wound probed to bone (18.3 vs. 2.0%, P < 0.001,
      chi 2 = 31.5, odds ratio (OR) = 11.1, CI = 4.0-30.3). Patients with infection and
      ischemia were nearly 90 times more likely to receive a midfoot or higher
      amputation compared with patients in less advanced wound stages (76.5 vs. 3.5%, P
      < 0.001, chi 2 = 133.5, OR = 89.6, CI = 25-316). CONCLUSIONS: Outcomes
      deteriorated with increasing grade and stage of wounds when measured using the
      University of Texas Wound Classification System.

PMID- 9589256
TI  - International Diabetes Federation meeting, 1997. Type 2 diabetes: its prevalence,
      causes, and treatment.

PMID- 9589257
TI  - Effect of insulin administration on serum lipoprotein(a) and its phenotypes in
      new-onset IDDM patients.

PMID- 9589258
TI  - Lispro insulin is suitable for external pumps but not for implantable pumps.

PMID- 9589259
TI  - Enhanced subclinical coagulation activation during diabetic ketoacidosis.

PMID- 9589260
TI  - Application of the revised American Diabetes Association criteria for the
      diagnosis of diabetes in a Canadian Native population.

PMID- 9589261
TI  - Use of a laser skin perforator for determination of capillary blood glucose
      yields reliable results and high patient acceptability.

PMID- 9589262
TI  - Glucose intolerance in pregnant women and its effects on newborn outcomes.

PMID- 9589263
TI  - Cannula occlusion with use of insulin lispro and insulin infusion system.

PMID- 9589264
TI  - Culturally appropriate lifestyle interventions in minority populations. More than
      meets the eye?

PMID- 9589265
TI  - Diabetes and accident insurance.

PMID- 9589266
TI  - Detection of microalbuminuria with the Micral-Test II test strip.

PMID- 9589267
TI  - Effects of buprenorphine and naloxone in morphine-stabilized opioid addicts.
AB  - The present study, conducted as part of the development of a
      buprenorphine/naloxone combination product, was designed to evaluate the
      individual and combined effects of intravenously administered buprenorphine and
      naloxone. This in-patient trial used a randomized, double-blind, crossover
      design. Ten opioid-dependent male subjects were stabilized and maintained on
      morphine, 15 mg given intramuscularly four times daily. Then, at 48- to 72-h
      intervals, subjects received one of the following by intravenous injection: (1)
      placebo, (2) morphine 15 mg, (3) buprenorphine 2 mg, (4) buprenorphine 2
      mg/naloxone 0.5 mg, and (5) naloxone 0.5 mg. Both naloxone and
      buprenorphine/naloxone produced significant (P < 0.005) opioid withdrawal effects
      compared to placebo as assessed with the CINA scale, an instrument which utilizes
      subject- and observer-reported, as well as physiological parameters. The
      combination of buprenorphine with naloxone in a 4:1 ratio produced opioid
      antagonist-like effects which should limit its potential for intravenous abuse by
      opioid addicts.

PMID- 9589268
TI  - Psychiatric symptom severity in cocaine-dependent outpatients: demographics, drug
      use characteristics and treatment outcome.
AB  - Psychiatric symptom severity and associated characteristics were assessed in 185
      individuals seeking outpatient treatment for cocaine dependence. The sample was
      divided into groups of low, medium and high psychiatric symptom severity based on
      Addiction Severity Index psychiatric composite scores. Patients with high symptom
      severity reported poorer pre-treatment functioning and more adverse consequences
      of cocaine use than the lower severity groups. Relationships between psychiatric
      severity and treatment outcome variables were assessed in a subset of 123
      patients who received one of three 24-week psychosocial treatments for cocaine
      abuse: (i) behavioral treatment with a voucher-based incentive program; (ii) the
      same behavioral treatment without vouchers; (iii) or drug abuse counseling.
      Psychiatric symptom severity failed to influence treatment outcome with any of
      these treatments. Thus, in this study the authors found no evidence to indicate
      that high psychiatric severity predicts poor response to psychosocial treatment
      for cocaine abuse.

PMID- 9589269
TI  - Dependence symptoms but no diagnosis: diagnostic 'orphans' in a community sample.
AB  - To receive a DSM-IV diagnosis of alcohol dependence, an individual must manifest
      at least three out of seven possible dependence criteria. Thus, individuals may
      manifest one or two dependence criteria yet not receive the dependence diagnosis.
      In a sense, these latter individuals may be seen as diagnostic 'orphans', since
      they have individual symptoms of dependence but no diagnoses. A study of these
      individuals sheds light on the validity of the three-symptom severity threshold
      for a diagnosis of DSM-IV alcohol dependence. Thus, we investigated the meaning
      of the 'orphan' status through cross-sectional and longitudinal research in a
      general population sample. Three groups were compared at baseline, subjects with
      no symptoms of any alcohol use disorder (148), diagnostic 'orphans' with one or
      two symptoms of dependence (136) and subjects who met full criteria for DSM-IV
      alcohol dependence (140). Several variables significantly differentiated the
      three groups, including binge drinking and family history of alcoholism. At a 1
      year follow-up point, very few of the 'orphans' met criteria for DSM-IV alcohol
      dependence. The proportion of new onsets from the 'orphan' group and the group
      with no symptoms did not differ significantly. Binge drinking predicted
      chronicity of 'orphan' status, but family history of alcoholism did not. The
      results support the decision to require a minimum of three symptoms to make a
      diagnosis of alcohol dependence.

PMID- 9589270
TI  - Cannabis dependence, withdrawal, and reinforcing effects among adolescents with
      conduct symptoms and substance use disorders.
AB  - The prevalence of cannabis use is rising among adolescents, many of whom perceive
      little risk from cannabis. However, clinicians who treat adolescent substance
      users hear frequent reports of serious cannabis-use disorders and problems. This
      study asked whether cannabis produced dependence and withdrawal among such
      patients, and whether patients' reports supported previous laboratory findings of
      reinforcing effects from cannabis. This was a screening and diagnostic study of
      serial treatment admissions. The diagnostic standard was the DSM-III-R dependence
      criteria, and the setting was a university-based adolescent substance treatment
      program with male residential and female outpatient services. The patients were
      165 males and 64 females from consecutive samples of 255 male and 85 female 13-19
      year-olds referred for substance and conduct problems (usually from social
      service or criminal justice agencies). Eighty-seven patients were not evaluated,
      usually due to early elopement. Twenty-four others did not meet study admission
      criteria: > or = one dependence diagnoses and > or = three lifetime conduct
      disorder symptoms. The main measures were items from diagnostic interview
      instruments for substance dependence, psychiatric disorders, and patterns of
      substance use. Diagnoses were substance dependence, 100%; current conduct
      disorder, 82.1%; major depression, 17.5%; attention-deficit/hyperactivity
      disorder, 14.8%. The results show that most patients claimed serious problems
      from cannabis, and 78.6% met standard adult criteria for cannabis dependence. Two
      thirds of cannabis-dependent patients reported withdrawal. Progression from first
      to regular cannabis use was as rapid as tobacco progression, and more rapid than
      that of alcohol, suggesting that cannabis is a reinforcer. The data indicate that
      for adolescents with conduct problems cannabis use is not benign, and that the
      drug potently reinforces cannabis-taking, producing both dependence and
      withdrawal. However, findings from this severely affected clinical population
      should not be generalized broadly to all other adolescents.

PMID- 9589271
TI  - Neuropsychological functioning in drug abusers.
AB  - The present study examined differences in neuropsychological performance among
      chronic cocaine, alcohol, and polysubstance abusers. A comprehensive
      neuropsychological battery was completed by 355 incarcerated adult male felons
      who were classified by DSM-IV criteria into four subgroups: (1) alcohol
      dependence or abuse (ETOH) (n = 101), (2) cocaine dependence or abuse (COC) (n =
      60), (3) polysubstance dependence or abuse (POLY (n = 56), and (4) a group of age
      and education matched adult male felons with no history of drug abuse (n = 138).
      Results showed no significant differences in neuropsychological performance
      between COC and control subjects. However, both the POLY and ETOH groups were
      found to perform significantly worse on nearly all measures compared to the COC
      and control groups. Further, analysis of neuropsychological domains showed the
      POLY group to perform significantly worse compared to the other groups in the
      areas of short-term memory, long-term memory and visual motor ability.
      Correlations between neuropsychological performance and length of abstinence from
      drug use showed the ETOH group to have made the greatest amount of improvement on
      individual measures and domains. The COC group showed the least amount of
      improvement, but their performance was not significantly different from controls.
      Results provide further support for the differential effects of drug use on
      neuropsychological functioning.

PMID- 9589272
TI  - Methadone treatment in the Scottish context: outcomes of a community-based
      service for drug users in Lothian.
AB  - Few studies investigating the effectiveness of methadone treatment for opiate
      dependence have emanated from the UK. The core feature of treatment offered by
      Lothian Health's Community Drug Problems Service involves the prescribing of
      methadone by the client's general practitioner. Of a cohort of 494 daily users of
      opiates attending the service, 39% remained in treatment for at least 12 months.
      Up to 2 years in-treatment follow-up revealed significant improvement in
      injecting and criminal behaviour. There were no HIV seroconversions reported
      during the treatment period. There was no improvement in injection equipment
      sharing, condom use, illicit drug use or employment status. 'Satisfactory'
      discharge was achieved for 40% of those in treatment for at least 6 months. These
      results are largely consistent with the outcomes of methadone programmes
      elsewhere.

PMID- 9589273
TI  - Contributions of the social context to the development of adolescent substance
      use: a multivariate latent growth modeling approach.
AB  - This article demonstrates a latent growth curve methodology for analyzing
      longitudinal data of adolescent substance use. Hypotheses concerning the form of
      growth in alcohol, cigarette, and marijuana use, and covariates influencing the
      form of growth, were tested. Participants were male and female adolescents (n =
      664) assessed at three time points. A common trajectory existed across the
      developmental period with significant increases in all three substances. Second
      order multivariate extensions of the basic latent growth modeling framework
      suggested that associations among the individual differences parameters,
      representing growth or change in the various substance use behaviors, could be
      adequately modeled by a higher-order substance use construct. Inept parental
      monitoring, parent-child conflict, peer deviance, academic failure, gender, and
      age, were significant predictors of initial levels and the trajectory of
      substance use.

PMID- 9589274
TI  - Increasing employment of opioid dependent outpatients: an intensive behavioral
      intervention.
AB  - The impact of a new, mandatory employment requirement in a community-based
      methadone treatment program was evaluated. All patients who had been in the
      methadone substitution program for at least 1 year but who were not currently
      employed (n = 36) were required to enhance their treatment with 20 h of
      employment (paid or volunteer). Patients with significant psychiatric or medical
      disabilities were excluded from the routine treatment requirement. Patients were
      informed by counseling staff that they had 2 months to secure employment. Those
      who did not accomplish the goal within that time period were transferred to more
      intensive weekly counseling (i.e. up to 8 h/week) for 10 weeks, with the enhanced
      counseling focusing primarily on resistance to the employment goal. Patients who
      remained resistant to the treatment plan were eventually started on a 21 day
      methadone taper until employment was verified. Seventy-five percent of the
      patients secured employment and maintained the position for at least 1 month.
      Positions were found in an average of 60 days. Most patients (78%) continued
      working throughout the 6-month follow-up. Those who failed to find work or
      maintain employment engaged in more illicit drug use. These results demonstrate
      that behavioral contingencies can motivate many methadone maintenance patients to
      obtain verified employment in the community.

PMID- 9589275
TI  - Effects of tizanidine administration on precipitated opioid withdrawal signs in
      rats.
AB  - An opioid withdrawal syndrome was precipitated by naloxone administration in rats
      treated with morphine. The withdrawal caused alteration of several physiological
      signs. The aim of the study was to investigate whether the altered physiological
      profiles were modified by utilising tizanidine, an alpha 2 adrenergic receptor
      agonist which is capable of affecting faecal and urinary excretion, rectal
      temperature, pain threshold levels and salivation. To induce an opioid withdrawal
      syndrome, morphine was administered in three daily intraperitoneal injections for
      four days at doses of 9, 16 and 25 mg/kg (1st day), 25, 25 and 50 mg/kg (2nd
      day), 50, 50 and 50 mg/kg (3rd day) and 50, 50 and 100 mg/kg (4th day): naloxone
      was injected (30 mg/kg) i.p. 180 min after the last morphine injection.
      Tizanidine was administered orally at 0.17, 0.35 and 0.7 mg/kg, 60 min after the
      last morphine injection. Signs such as faecal and urine excretion, rectal
      temperature and latency times to thermal stimulus, salivation, jumping and wet
      dog shakes were affected in different ways by morphine, naloxone, tizanidine and
      by the combination of these agents. Notably, the administration of tizanidine in
      rats receiving morphine and naloxone decreased the intensity of certain
      withdrawal symptoms, including altered excretion of faeces and urine, salivation
      and wet dog shake behavior. Body temperature levels and nociceptive threshold
      values were also modified. The effects caused by tizanidine administration may be
      due to its alpha 2 receptor agonist activity interfering with a mechanism
      involved in the regulation of these previously mentioned withdrawal symptoms.
      Thus, the use of this drug may be indicated as a possible control of the acute
      phase of opioid withdrawal in heroin addicts.

PMID- 9589277
TI  - Elementary particles for models of drug dependence 10th Okey Memorial Lecture
      presented at the Institute of Psychiatry, London on 19th March 1997.

PMID- 9589278
TI  - The small and the ordinary: the daily practice of a postmodern narrative therapy.
AB  - In this article, I contrast assumptions of a modernist worldview and a postmodern
      worldview as they relate to clinical practice. Two exercises are described that
      help therapists develop insight into and practice with the kind of thinking that
      is consistent with a postmodern narrative clinical practice. Particular attention
      is paid to the ways that even the small and the ordinary--single words, single
      gestures, minor asides, trivial actions--can provide opportunities for generating
      new meanings. Five concepts that I routinely use in my professional and personal
      life and that are consistent with a postmodern narrative practice--discourse,
      externalizing the internalized discourse, exceptions, power as the means to
      produce a consensus, and characteristics of narrative--are illustrated.

PMID- 9589279
TI  - Transforming narratives: a change event in constructivist family therapy.
AB  - One important clinical task in family therapy involves transforming the client's
      construction of the presenting problem from an individual, intrapersonal view to
      an interpersonal, relational, or systemic one (Sluzki, 1992). To study the
      transformation process in initial sessions, we sampled 8 families in which the
      referring parent requested help for a child's problem. The 8 therapists, trained
      and experienced in Sluzki's (1992) narrative approach, attempted to facilitate a
      transformation in the parents' initial construction of the problem. In 4
      sessions, the transformation was independently judged to be successful by the
      therapist and observers, while in 4 other sessions the transformation was judged
      to be unsuccessful. Videotapes of the 8 interviews were analyzed qualitatively,
      and the parents' verbatim descriptions of the problem were coded using the
      Cognitive Constructions Coding System (Friedlander, 1995). We compared the
      successful and the unsuccessful sessions and developed a conceptual model of the
      successful transformation process that included client performances as well as
      therapist operations (Greenberg, 1986). While many elements in the model were
      consistent with Sluzki's (1992) "blue-print" transformation, several new elements
      were added. Practical implications are described, along with limitations and
      recommendations for future research.

PMID- 9589280
TI  - Children's attributions about family arguments: implications for family therapy.
AB  - Children's attributions about the causes of family arguments affect both their
      interpretations of the meaning of and their adjustment to such events. Children's
      attributions about family arguments are, therefore, of importance in family
      therapy, especially for therapists who work from a cognitive or constructivist
      perspective. In an exploratory study, we examined children's attributions about
      family arguments in two arenas: marital arguments and parent-child arguments.
      Ninety-two children, aged 5-12, listened to an audiotaped argument and answered a
      series of structured questions concerning different attributions about the causes
      of such arguments. Descriptive analyses of the most and least endorsed
      attributions provided an overall map of the "stories" children tell about the
      causes of family arguments, and showed that, in general, they are more likely to
      endorse multiple, interacting causes than internal, blaming attributions.
      Additionally, children of all ages made somewhat different attributions
      concerning mothers vs. fathers in marital arguments. Implications for family
      therapy and suggestions for future clinical research are discussed.

PMID- 9589281
TI  - The systemic view of violence: an ethical perspective.
AB  - Systems theory has been critiqued by a number of feminist writers who felt that
      it did not adequately address the issues of violence and male domination in
      families. This essay argues that systems theory describes the world from an
      "exogenic" perspective--the scientific world of nature, which is intrinsically
      amoral. In the exogenic world all causality is circular, as nature maintains a
      system that has survived for billions of years. Bateson found "mind" to be within
      the system of nature, implying that mind must also be amoral. However, most
      people view the world from an "endogenic" perspective, a personal construction of
      reality molded by the environment in which they live, and which inevitably
      incorporates morality. Humans believe that violence is wrong, not for
      intellectual reasons, but for moral reasons. Implications for therapy are
      presented. A postmodern or constructivist position is taken as a way to
      acknowledge the influence of relationships on problems and definitions of
      problems, while allowing for a moral or legal consensus to pervade the
      therapeutic enterprise.

PMID- 9589282
TI  - Family therapy with a multiparental/multispousal family.
AB  - This article examines therapy with a Bedouin-Arab family from the Negev, Israel,
      which consisted of 69 members: a husband, 8 wives, and 60 siblings. The husband,
      who lived with his youngest wife, paid little attention to his other wives and
      their children. There was considerable competition, hostility, and jealousy among
      the wives; no communication between the co-wives or the children of different
      wives; and a variety of behavioral and psychosocial problems among family
      members. I describe the varied strategies and systems involved in family therapy.
      The main strategies were to establish good relationships among the co-wives and
      to build a coalition among them, including the youngest wife, through group
      therapy in a medical clinic. A secondary strategy was using the children's
      problems to get the husband involved in the therapy. With improvement of the
      children's functioning, and with reduced intra-subfamily hostility, the husband's
      relationships with his children and wives improved.

PMID- 9589284
TI  - Comparison of schizophrenic patients' families and normal families in China,
      using Chinese versions of FACES-II and the Family Environment Scales.
AB  - The lack of measures that systematically evaluate the characteristics and
      functioning of Chinese families is hindering the development of appropriate
      family interventions for schizophrenia in China. We assessed the reliability and
      validity of revised and adapted Chinese versions (CV) of the Family Adaptability
      and Cohesion Evaluation Scales (FACES-II-CV) and the Family Environment Scales
      (FES-CV) and administered these instruments to 120 respondents from families with
      a schizophrenic member and 126 respondents from control families. The
      psychometric properties of the FACES-II-CV and of the FES-CV Cohesion, Conflict,
      Intellectual-Cultural Orientation, and Active-Recreational Orientation scales are
      satisfactory, so they are appropriate for use in China; the remaining six FES-CV
      scales require further culturally appropriate revision. Compared to control
      families, families with schizophrenic patients in China have higher conflict,
      lower cohesion, poor adaptability, and are less likely to be involved in
      intellectual and recreational activities. These differences remained significant
      after adjusting for family and respondent characteristics.

PMID- 9589283
TI  - Parent-adolescent conflict and stress when parents are living with AIDS.
AB  - Parental perceptions of conflict and stress with their adolescent children are
      described, and their associations with demographic factors, physical health, and
      lifestyle are examined. Adolescent-parent conflicts, parenting stress, and
      parents' health, substance use, and sexual lifestyle were assessed among 151
      parents living with AIDS. Parents living with AIDS reported a mean of 3.3 (SD =
      1.3) areas of conflict with their adolescents and 1.5 (SD = 1.7) stressful
      parenting events over the previous 3 months. The parents were very ill, with many
      physical symptoms and diseases. Simultaneously, substance use was common (17%
      used daily), but not injection drug use (3.3%). Half had a sexual partner (63%
      protected their partners by using condoms consistently). Regression analysis
      revealed that parent-adolescent conflict was significantly associated with high
      parental drug use; stressful parenting events were significantly related to the
      lifestyle (high drug use and frequent sex acts) of Latino and African American
      parents, but not of white parents. Results of the analysis indicate that, in
      contrast to parents with other illnesses, parent-adolescent conflict and
      stressful parenting events were not influenced by parents' health status, but
      were significantly influenced by substance use and sexual lifestyles.

PMID- 9589285
TI  - Evaluating therapist competency and adherence to behavioral family management
      with bipolar patients.
AB  - The present study assessed fidelity to the behavioral family management (BFM)
      model for treating bipolar disorder patients and their families. The BFM
      Therapist Competency/Adherence Scale (BFM-TCAS) was developed to evaluate
      clinicians' competency and adherence to BFM, as outlined by Miklowitz' (1989) BFM
      Manual for use with bipolar patients. Therapist competency and treatment
      adherence was also evaluated with regard to two family characteristics: overall
      level of family difficulty and family expressed emotion (EE) status. The BFM-TCAS
      was used to code 78 videotaped sessions of 26 families with a bipolar member,
      selected from a larger treatment study of bipolar disorder patients. The findings
      suggest that, overall, clinicians adhered closely to the BFM manual. Specific
      areas in which there was high competency and treatment adherence were (a) skill
      in conveying factual information about bipolar illness, (b) establishment of a
      therapeutic environment, and (c) ability to take command of therapy sessions. The
      one area in which there was less competency and relatively weak adherence to the
      manual was the use of between-session homework assignments to assist families in
      mastering the BFM exercises. Results of this study also suggest that, for the
      most part, therapist competency and adherence ratings were not related to overall
      level of difficulty or to family EE status.

PMID- 9589286
TI  - Invoking natural law.

PMID- 9589287
TI  - Seeding the cloning debate.

PMID- 9589288
TI  - Bad copies. How popular media represent cloning as an ethical problem.
AB  - The media, perhaps more than any other slice of culture, influence what we think
      and talk about, what we take to be important, what we worry about. And this was
      especially true when news of Dolly hit the airwaves and newstands. Most Americans
      received training in the ethics of cloning before they knew what cloning was.
      Media coverage fixed the content and outline of the public moral debate, both
      revealing and creating the dominant public worries about cloning humans. The
      primary characterization of cloning as an ethical issue centers around three
      connected concerns: the loss of human uniqueness and individuality, the
      pathological motivations of a cloner, and the fear of out-of-control scientists.

PMID- 9589290
TI  - Hard cases.

PMID- 9589289
TI  - A defense of the whole-brain concept of death.
AB  - The concept of whole-brain death is under attack again. Scholars are arguing that
      the concept of brain death per se--regardless of the focus on "higher," "stem" or
      "whole"--is fundamentally flawed. These scholars have identified what they
      believe are serious discrepancies between the definition and criterion of brain
      death, and have pointed out that medical professionals and lay persons remain
      confused about its meaning. Yet whole-brain death remains the standard for
      determining death in much of the Western world and its defenders believe this
      concept best maps onto our everyday conception of death.

PMID- 9589292
TI  - [Rational phytotherapy: news in the therapy of acute and chronic sinusitis].

PMID- 9589293
TI  - Dose-ranging study of mesalamine (PENTASA) enemas in the treatment of acute
      ulcerative proctosigmoiditis: results of a multicentered placebo-controlled
      trial. The U.S. PENTASA Enema Study Group.
AB  - The safety and efficacy of mesalamine enemas were determined ina dose-ranging
      study enrolling 287 patients with ulcerative proctitis and proctosigmoiditis in a
      double-blind, placebo-controlled, multicenter trial. Patients were randomized to
      receive placebo, 1, 2, or 4 g in 100 ml mesalamine (PENTASA) enemas h.s. for 8
      weeks. Efficacy was assessed by clinical, sigmoidoscopic, and histologic
      improvement, as well as by induction of remission. Sixty-seven percent, 65%, and
      75% of patients receiving 1-, 2-, and 4-g enemas were markedly improved according
      to the physician's global assessment compared with 27% of patients treated with
      placebo. The mean improvement in sigmoidoscopic index was 5.8, 5.9, and 6.4
      points (on a 15-point scale) for the 1-, 2-, and 4-g enema groups compared with a
      decrease of 1.8 points for the placebo group. Improvement in biopsy scores was
      observed in 47, 55, and 59% of 1-, 2-, and 4-g groups contrasted with 27% of the
      placebo-treated patients. All three doses were significantly more effective than
      placebo in reducing symptoms and trips to the toilet compared with placebo. No
      dose-response relation was demonstrated. The safety profile was similar to that
      of placebo. In conclusion, mesalamine enemas are effective as a single agent in
      the short-term treatment of distal ulcerative colitis without an apparent dose
      response between 1 and 4 g nightly.

PMID- 9589291
TI  - Last chance therapies and managed care. Pluralism, fair procedures, and
      legitimacy.
AB  - How can health plans make fair determinations about when "experimental" (and
      costly) treatments such as high dose chemotherapy with autologous bone marrow
      transplantation should be covered despite lack of clear clinical consensus about
      their benefits? Different models for managing "last chance" therapies evolving in
      some health plans offer promising examples of how issues of fairness and
      legitimacy in decision-making can be addressed.

PMID- 9589294
TI  - Distribution of acute bowel inflammation determined by technetium-labeled white
      blood cells in children with inflammatory bowel disease.
AB  - Knowledge of the distribution of disease in patients with inflammatory bowel
      disease is important because it has diagnostic, prognostic, and therapeutic
      implications. We studied 215 patients with 99mTc-HMPAO-white blood cell scans, of
      whom 80 had Crohn's disease (CD), 34 had active ulcerative colitis (UC), and 31
      were controls. In our 77 cases of active CD, uptake was seen exclusively in the
      small bowel in 18% of patients, only the large bowel in 44%, and both the large
      and small bowel in 38% of patients. Discontinuous colitis was seen in 63 of these
      patients. In the 29 cases of active UC, the uptake involved the entire colon in
      50% of patients, extended farther than the sigmoid in 27% of patients, and was
      limited to the rectosigmoid in 23%. In the 29 cases of active UC, four of the
      scans incorrectly revealed discontinuous accumulation of 99mTc-HMPAO-WBC. In 31
      controls, no significant colonic uptake was seen. Isolated small bowel
      involvement with CD is observed less frequently in children undergoing 99mTc
      HMPAO-WBC scanning than in adults. In children, the segmental distribution of
      inflammation as depicted with 99mTc-HMPAO-WBC is similar to the radiologic
      distribution.

PMID- 9589295
TI  - Bile composition in patients with ileal resection due to Crohn's disease.
AB  - Patients with Crohn's disease (CD) have an increased risk of developing
      gallstones, but the mechanisms are unknown. In a previous study, we found a
      subnormal cholesterol saturation in the bile of patients with short ileal
      resections due to CD. The aim of this study was to test the hypothesis that (a)
      CD patients with a long ileal resection have an altered biliary composition and
      (b) that CD patients with short or long ileal resection have an increased content
      of bilirubin in their bile. Biliary lipid composition, cholesterol saturation,
      bile acid pattern, and bilirubin concentration were determined in fasting
      duodenal bile of 10 CD patients with long ileal resections and in 4 patients with
      short resections. Ten healthy subjects served as controls. Cholesterol saturation
      was significantly lower in those CD patients who had a long or short resection
      compared with the healthy subjects. Bile acid composition in the CD patients was
      characterized by a significant decrease in the deoxycholic acid fraction and a
      prominent increase in the ursodeoxycholic acid fraction. The bilirubin
      concentrations, expressed as micromoles of bilirubin per millimole bile acid,
      were 45-50% higher in patients who had a long or a short ileal resection compared
      with healthy controls. Based on these results, CD patients who had had an ileal
      resection seem not to be at an increased risk of cholesterol gallstone formation
      but rather at risk of developing pigment stones.

PMID- 9589296
TI  - Severe bone pain as an adverse effect of cyclosporin therapy for Crohn's disease.
AB  - A case of severe bone pain associated with cyclosporin therapy for Crohn's
      disease is reported. Severe leg pain developed in a 32-year-old man who was
      receiving cyclosporin for Crohn's disease that was refractory to medical
      management. Leg pain was related to the dose of cyclosporin, improved with
      calcium channel blockade, and resolved on discontinuation of cyclosporin. This
      syndrome has been described in the renal transplantation literature and may be
      related to vasoconstriction of bone vasculature.

PMID- 9589297
TI  - Simultaneous onset of pyoderma gangrenosum and bitemporal abscesses of the upper
      eyelids during a flare of ulcerative colitis.
AB  - A case of simultaneous appearance of bitemporal sterile abscesses of the upper
      eyelids and pyoderma gangrenosum in an 80-year-old woman with an acute flare of
      ulcerative colitis is described. Therapy with high-dose corticosteroids led to
      healing of the skin and upper eyelid lesions and induced remission of ulcerative
      colitis.

PMID- 9589298
TI  - Challenges in designing a randomized trial of surveillance colonoscopy in IBD.

PMID- 9589299
TI  - Cutaneous manifestations of inflammatory bowel disease.

PMID- 9589300
TI  - Endothelial ligands and homing of mucosal leukocytes in extraintestinal
      manifestations of IBD.
AB  - Crohn's disease and ulcerative colitis are quite often complicated with
      manifestations in extraintestinal organs like joints, eye, and skin. Although the
      etiopathogenesis of these nonmucosal complications remains unsettled, they all
      share the characteristic feature of inappropriate leukocyte recruitment in
      nonlymphatic organs. Under normal conditions, lymphocytes recirculate between the
      blood and lymphoid organs in search of their cognate antigens, whereas
      polymorphonuclear leukocytes are excluded from tissues. On inflammation, the
      leukocyte trafficking changes dramatically. Granulocytes infiltrate into the
      inflammatory focus very rapidly, and they are followed by lymphocytes, especially
      activated immunoblasts and memory cells, which now also leave the vasculature at
      nonlymphoid tissues. Leukocyte extravasation from the blood into the tissue is a
      multistep process governed by sequential interactions between adhesion molecules
      expressed on the surface of leukocytes and their ligands on the luminal side of
      the endothelial cells lining the vessels. In this review, we describe the
      recirculation routes of mucosal lymphocytes in physiologic conditions, as well as
      the changes seen in mucosal and extramucosal homing in inflammatory bowel disease
      (IBD). We present a working model of how adhesive molecular interactions between
      mucosal immune cells and endothelial cells may explain the pathogenesis of the
      development of inflammatory cell infiltrate in distant organs in IBD, and how
      this information may help to plan new antiadhesive therapeutic strategies.

PMID- 9589301
TI  - Proteolytic enzymes in inflammatory bowel disease.

PMID- 9589302
TI  - How do you treat refractory pouchitis and when do you decide to remove the pouch?

PMID- 9589303
TI  - How do you treat refractory pouchitis and when do you decide to remove the pouch?

PMID- 9589304
TI  - URSO not so good for PSC.

PMID- 9589305
TI  - Anti-tumor necrosis factor alpha: Crohn's disease guided missile.

PMID- 9589306
TI  - Where oh where has my little pouch gone? The case of the lost pouch.

PMID- 9589307
TI  - Nourishing the body through use of process prescriptions in group therapy.
AB  - OBJECTIVE: This clinical report describes a creative process for developing
      between-session prescriptions which sustain and strengthen the momentum of change
      occurring in group treatment sessions. METHOD: Therapists in this model use words
      and phrases depicting the group as a body in order to guide the treatment process
      and develop between-session prescriptions. Maintaining a perspective of the
      treatment group as a body facilitates development of member commitment to the
      well-being of a physical and psychological body, and between-session assignments
      employ the developmental phases of the therapy for illuminating the disorder and
      effecting its resolution. This approach was developed in an ongoing, open-ended
      treatment group provided at a community mental health center for 14 years.
      RESULTS: Examples are presented of process prescriptions which simultaneously
      address several dynamic levels: (a) the theme of interactions between the
      individuals in each session; (b) the particular stage of the group's development,
      and the ways this level of maturation determines how interactions arise and
      themes are selected; and (c) the underlying functions of the eating disorder.
      DISCUSSION: Using the metaphor of the body to guide the language of between
      session prescriptions links developmental group treatment process with members'
      day-to-day engagement with the eating disorder. By participating directly in the
      development of the treatment experience, the group members become committed to a
      developmental process that engages them in accountability and caring for a body,
      and, by extension, their own bodies.

PMID- 9589308
TI  - The clinical utility of randomized controlled trials.
AB  - OBJECTIVE: Efficacy studies using randomized controlled trials (RCTs), on which
      empirically supported treatments are based, are often rejected as having little
      if any relevance to clinical practice. RCTs are faulted for allegedly excluding
      poor prognosis patients and therapists and treatments that are unrepresentative
      of clinical practice. METHODS: Evidence on the generalizability of findings from
      RCTs to diverse patient populations, different therapists, and varied clinical
      settings is critically evaluated. RESULTS: Existing research indicates that RCTs
      commonly include patients with multiple problems and levels of disturbance as
      severe as patients in clinical settings. DISCUSSION: The applicability of the
      findings of RCTs to clinical practice will be a changing function of the nature
      of the particular study and clinical setting to which the results are to be
      generalized. Future research should address the clinical utility of the findings
      of efficacy studies across different patient populations, therapists, and
      treatment methods.

PMID- 9589309
TI  - Factors associated with weight concerns in adolescent girls.
AB  - OBJECTIVE: This study examined the association of weight concerns with potential
      risk factors for the development of eating disorders. METHOD: A self-report
      survey was given to 103 elementary (Grades 4 and 5) and 420 middle (Grades 6-8)
      school students in Arizona and California. Of these, 78 elementary and 333 middle
      school students provided complete data and were used in the analyses. RESULTS: In
      a multivariate stepwise regression analysis, the importance that peers put on
      weight and eating was most strongly related to weight concerns in the elementary
      school girls, accounting for 34% of the variance after adjusting for site
      differences. Trying to look like girls/women on TV and in magazines as well as
      body mass index (BMI) entered the final model that accounted for 57% of the
      variance in weight concerns. In middle school, the importance that peers place on
      weight and eating was also the strongest predictor accounting for 33% of the
      variance followed by confidence, BMI, trying to look like girls/women on TV and
      in magazines, and being teased about weight. Together these variables accounted
      for 55% of the variance. DISCUSSION: Prevention programs aimed at reducing weight
      concerns need to address these factors.

PMID- 9589311
TI  - Weight gain after smoking cessation in women: the impact of dieting status.
AB  - OBJECTIVE: The fear of weight gain appears to be a barrier to quitting in some
      smokers, particularly in women. However, not all female smokers have the same
      concerns about weight, and not all quitters are equally susceptible to gaining
      weight after cessation. We hypothesized that among females, dieters, compared to
      nondieters, would report more weight gain after smoking cessation and would tend
      to smoke more for weight control purpose. METHOD: Undergraduate college students
      were surveyed to assess their smoking status, dieting status, postcessation
      weight gain, and their motivations to smoke. RESULTS: Among former smokers,
      dieters reported considerably more weight gain than nondieters. Dieters were more
      likely to have started, and to have continued smoking in order to control their
      weight, and among current smokers, dieters reported having had shorter quit
      attempts. DISCUSSION: The dieters/former smokers' comparatively high weight gain
      after smoking cessation is discussed in terms of possible changes in dietary
      intake, metabolic rate, and physical activity.

PMID- 9589310
TI  - Correlates of binge eating in Hispanic, black, and white women.
AB  - OBJECTIVE: We sought to compare the severity and correlates of binge eating in
      White, Black, and Hispanic women. METHOD: Our sample consisted of 351 (55 White,
      179 Black, and 117 Hispanic) women who were assessed on three proposed factors
      associated with binge eating (weight, depression, and ideal body image). RESULTS:
      Our results showed that binge eating symptoms were more severe in our sample of
      Hispanic versus Black or White women. Across all ethnic groups, women who binged
      more were heavier, more depressed, and preferred a slimmer body ideal. Binge
      eating severity was predicted by weight and depression in Hispanics and by
      depression in Whites. None of the proposed factors significantly influenced binge
      eating in Blacks. DISCUSSION: These results show ethnic differences in the
      correlates of binge eating and highlight the need for further comparative
      research on aberrant eating patterns.

PMID- 9589312
TI  - The disorder-salient stroop effect as a measure of psychopathology in eating
      disorders.
AB  - OBJECTIVES: The aim was to assess, using sophisticated experimental methods, the
      amount of interference on a Stroop task in patients with eating disorders, under
      conditions of blocked and mixed stimulus presentation. METHODS: Patients with
      eating disorders and non-patients named the color in which a word was displayed.
      Words came from an experimental category (food/eating, weight/shape, "emotion,"
      or affectively neutral word) or from a matched set of unrelated control words.
      Color-naming latencies were compared in a blocked condition, with words from just
      one set in each block, and in a mixed condition, with a mixture of word types in
      each block. RESULTS: In the mixed condition, patients took longer to color-name
      food/eating and weight/shape words than control words. With blocked presentation
      this effect was magnified; and patients with bulimia nervosa also showed
      increased naming-latency for "emotion" words. Non-patients showed neither effect
      and no group showed interference for the affectively neutral category. Patients'
      interference effects correlated reliably with self-reported depression and
      anxiety. DISCUSSION: Sources of interference and methodological and diagnostic
      implications are discussed.

PMID- 9589313
TI  - Preconscious processing of threat cues: impact on eating among women with
      unhealthy eating attitudes.
AB  - OBJECTIVE: This study examined the role of different forms of threat cues in
      generating eating behavior among nonclinical women with more or less healthy
      eating attitudes. METHOD: The participants were 60 non-eating-disordered women,
      divided into those with relatively high and low Eating Disorder Inventory (EDI)
      scores. An ego (self-esteem) threat, a physical threat, or a neutral message was
      presented subliminally via a tachistoscope, and the amount eaten subsequently was
      measured. RESULTS: The women with healthy eating attitudes ate slightly more
      after exposure to the ego threat, but not after the physical threat. The group
      with unhealthy eating attitudes ate more after exposure to both forms of threats,
      but particularly after the ego threat. CONCLUSIONS: A cognitive interpretation of
      these findings indicates preconscious activation of elaborate threat-related
      schemata among women with relatively unhealthy eating attitudes, leading to
      subsequent "escape" behavior (eating). Further testing is needed to elaborate on
      this phenomenon, it psychological substrates, and its therapeutic implications.

PMID- 9589314
TI  - Predicting level of restrained eating behavior in adult women.
AB  - OBJECTIVE: This study attempted to predict participants' level of restrained
      eating using the following psychological variables: body dissatisfaction,
      negative affect, self-esteem, and perceived problem-solving ability. METHODS:
      Because previous research relating to restrained eating has primarily focused on
      women between the ages of 18 and 25, women age 30 to 60 served as participants.
      In addition, this study attempted to investigate the unique and combined variance
      each psychological variable contributes to restrained eating. RESULTS: The
      results suggest that both body dissatisfaction and negative affect are
      significant predictors of level of restraint. DISCUSSION: Moreover, this study
      suggests that the concept of restrained eating is relevant to women over age 25.

PMID- 9589315
TI  - Is there a relationship between bulimia nervosa and hazardous alcohol use?
AB  - OBJECTIVE: The present study investigates the relationship between hazardous
      alcohol consumption and bulimia nervosa in a clinical population. METHOD: The
      Alcohol Use Disorders Identification Test (AUDIT) was administered to two groups
      of female subjects: patients with bulimia nervosa (n = 30) and nonbulimic
      controls (n = 15). These two groups were further subdivided on the basis of
      personality disorder as assessed by the Personality Disorder Examination (PDE), a
      comprehensive interview covering all of the criteria for the 13 DSM-III-R Axis II
      disorders. The bulimic patients were referred to a dieting disorders clinic
      affiliated with the University of Sydney. All met DSM-III-R criteria for bulimia
      nervosa and all had Body Mass Indices (BMIs) greater than 19. The nonbulimic
      control group were recruited from an undergraduate psychology course. All
      subjects were given the Bulimic Investigatory Test, Edinburgh (BITE) and the
      Eating Disorders Inventory-2 (EDI-2). RESULTS: 66.7% (8/12) of personality
      disordered bulimic patients were drinking at hazardous levels whereas 61.1%
      (11/18) of bulimic patients without a personality disorder were doing likewise.
      Furthermore, 35.7% (5/14) of the nonbulimic controls without personality
      disorders were drinking at hazardous levels and the only control subject with a
      personality disorder was doing likewise. The association between personality
      disorder diagnosis and hazardous alcohol use in the bulimic sample just failed to
      reach significance at the 5% level (chi 2 1,upper .05 = 3.84, p = .052). No
      association between Axis 1 diagnosis of bulimia nervosa and hazardous alcohol use
      was found (chi 2 1,upper .05 = 3.84, p = .52). DISCUSSION: The results of the
      present study suggest we may need to rethink the relationship between hazardous
      alcohol use and bulimia nervosa reported in the literature, as it may be an
      artifact of the relationship between personality disorder and hazardous alcohol
      consumption. Further research is necessary to clarify this issue.

PMID- 9589316
TI  - Eating disorders in British Asians.
AB  - OBJECTIVE: There has been a clinical impression that British Asians present with
      eating disorders less commonly than expected. The study examines the numbers and
      characteristics of Asians presenting to the Leicestershire Eating Disorders
      Service with a catchment area which includes a substantial proportion of people
      with a background in the Indian subcontinent. METHOD: Case note review and
      comparison of rates of presentation of people with and without such a background.
      RESULTS: Twenty-one eating-disordered Asians were seen in 10 years. Their
      clinical characteristics resembled the rest of the referrals. However, the rate
      of presentation of people from the Asian population was about one fourth of that
      of the white population. DISCUSSION: Asian women with eating disorders were
      referred less often. This might be because of a lower prevalence in this
      population. However, it seems likely there are variable and sometimes high
      threshold filters to secondary care for such women.

PMID- 9589317
TI  - Gender issues in the management of multi-impulsive bulimia: a case-study.
AB  - We describe the management of multi-impulsive bulimia nervosa in a 27-year-old
      man. Inpatient treatment was attempted using a standardized focal-interpretative
      (psychodynamic) and cognitive-behavioral approach, with an emphasis on ward
      milieu. The value of this approach has been proved for female patients in the
      past. To our knowledge, this is the first report of its usage for a male with
      multi-impulsive bulimia, and the problems encountered highlight the impact of
      gender on behavioral symptoms, ward culture, and the predominantly female patient
      group.

PMID- 9589318
TI  - Semen-like urethral discharge during the use of mazindol.
AB  - Two case reports are described of male patients experiencing a semen-like
      urethral discharge during micturition, suspected to be induced by mazindol.
      Mazindol has an indirect sympathomimetic action and is known to cause urogenital
      side effects such as urinary retention and testicular pain. It is suggested that
      seminal discharge may be added to this list.

PMID- 9589319
TI  - ESHO quality assurance guidelines for regional hyperthermia.
AB  - The Technical Committee and the Clinical Committee of the ESHO evaluated the
      experience of the institutes which are active in clinical regional hyperthermia
      using radiative equipment. Based on this evaluation, QA guidelines have been
      formulated. The focus of these guidelines lies on what must be done not on how it
      should be done. Subjects covered are: treatment planning, treatment, treatment
      documentation, requirements and characterization of equipment, safety aspects,
      hyperthermia staff requirements and instrumentation for quality assurance.

PMID- 9589321
TI  - Enhancement of thermoradiotherapy by glucose administration for superficial
      malignant tumours.
AB  - The effect of hyperglycemia on the thermoradiotherapy of superficial malignant
      tumours was investigated. Glucose administration alone (500 ml of 10% glucose by
      intravenous drip infusion) reduced the tumour blood flow, when measured by laser
      Doppler flowmetry, to 66.1% of the baseline level at 30 minutes after the
      beginning of glucose infusion. Forty patients received glucose in tandem during
      the hyperthermia and radiotherapy (group A), and 38 patients received
      thermoradiotherapy alone (group B). The mean Tave (the average temperature of all
      intratumoural sensors) in group A was 43.4 +/- 1.1 degrees C while that in group
      B was 42.5 +/- 1.2 degrees C, i.e., glucose administrations significantly
      increased the tumour temperature (p < 0.01). In group A, complete tumour response
      (CR) was observed in 12 patients (30.0%), partial response (PR) in 25 patients
      (62.5%) and no response (NR) in three patients (7.5%). In group B, seven (18.4%),
      20 (52.7%) and 11 (28.9%) patients showed CR, PR and NR, respectively. The tumour
      response rates were significantly different between two treatment groups (p <
      0.05). The frequency of side effects of hyperthermia in groups A and B were 22.5
      and 21.1%, respectively. This study suggests that hyperglycemia enhances the
      effectiveness of thermoradiotherapy.

PMID- 9589320
TI  - A comparison of reduced-order modelling techniques for application in
      hyperthermia control and estimation.
AB  - Reduced-order modelling techniques can make important contributions in the
      control and state estimation of large systems. In hyperthermia, reduced-order
      modelling can provide a useful tool by which a large thermal model can be reduced
      to the most significant subset of its full-order modes, making real-time control
      and estimation possible. Two such reduction methods, one based on modal
      decomposition and the other on balanced realization, are compared in the context
      of simulated hyperthermia heat transfer problems. The results show that the modal
      decomposition reduction method has three significant advantages over that of
      balanced realization. First, modal decomposition reduced models result in less
      error, when compared to the full-order model, than balanced realization reduced
      models of similar order in problems with low or moderate advective heat transfer.
      Second, because the balanced realization based methods require a priori knowledge
      of the sensor and actuator placements, the reduced-order model is not robust to
      changes in sensor or actuator locations, a limitation not present in modal
      decomposition. Third, the modal decomposition transformation is less demanding
      computationally. On the other hand, in thermal problems dominated by advective
      heat transfer, numerical instabilities make modal decomposition based reduction
      problematic. Modal decomposition methods are therefore recommended for reduction
      of models in which advection is not dominant and research continues into methods
      to render balanced realization based reduction more suitable for real-time
      clinical hyperthermia control and estimation.

PMID- 9589322
TI  - Ultrasound field calculation in a water-soft tissue medium.
AB  - An efficient numerical approximation for ultrasound field calculation in a two or
      three layer water-soft tissue medium is presented. It is extended from a method
      developed previously in a homogeneous medium. The emphasis of this study is to
      examine the conditions that are required for this approximation. Criteria are
      given for achieving an appropriate accuracy, which is verified by comparing it
      with the Rayleigh integral.

PMID- 9589323
TI  - Solid materials with high dielectric constants for hyperthermia applications.
AB  - The manufacture of solid components with high permittivities epsilon r of 1-100
      and differing conductivities sigma of 0-1.0 S/m has practical significance for
      fabricating applicators and phantoms in radiofrequency hyperthermia. For this
      purpose, various plastics (resins, polyurethane and silicone) were combined with
      additives (graphite and metal powder) and tested to assess their radiofrequency
      and mechanical characteristics and to identify manufacturing problems. Most of
      the plastics could be made highly dielectric and conductive by adding graphite in
      the range of muscle tissue (i.e. epsilon r approximately 80, sigma approximately
      0.8 S/m). However, there are major differences between the materials with respect
      to mechanical behaviour, durability, feasibility of manufacture, and
      reproducibility. Manufacturing water-equivalent plastics (low conductivity sigma
      < 0.05 S/m and epsilon r value of 70-80) is particularly difficult. A less filled
      polyester resin in which concentration of brass powder can achieve an epsilon r
      value of up to 100 at low conductivity proved to be the only suitable medium.
      Such a plastic can be used for future applicator designs. Other materials of
      interest include plastics equivalent to lossy media (e.g. sigma = 0.45-0.55 S/m,
      epsilon r = 70-80), fat-equivalent plastics (polyurethane with graphite) and
      higher dielectric flexible plastics (silicone with brass powder).

PMID- 9589324
TI  - Hyperthermic enhancement of tumour growth inhibition by accelerated carbon-ions
      in transplantable human esophageal cancer.
AB  - The study examined the effects of combination of hyperthermia (42 degrees C) and
      290 MeV/u carbon-ion (C-) beams or 200 kVp X-rays on tumour regrowth delay of
      transplantable human esophageal cancer as an in vivo model for radiotherapy of
      cancer. The C-beams were more effective in the tumour growth inhibition than X
      rays. The relative biological effectiveness (RBE) of C-beams against X-rays was
      2.00. It was observed that the interactive hyperthermic (42 degrees C, for 30
      min) enhancement of tumour regrowth delay by high-linear energy transfer (LET) C
      beams was similar to that of combination of low-LET X-rays with hyperthermia. The
      thermal enhancement ratios (TER) were 6.10 and 5.57 for X-rays and C-beams,
      respectively. These results suggest that hyperthermic treatment is effective in
      radiotherapy not only by low-LET radiation but also by high-LET radiation such as
      C-beams. In conclusion, the depression of the tumour growth by the combined
      treatment of hyperthermia (42 degrees C) and the C-beams strongly suggests the
      available possible application of interdisciplinary cancer therapy for refractory
      tumours.

PMID- 9589325
TI  - Tolerance of guinea pig hippocampal slice CA1 neurons to hyperthermia evaluated
      by orthodromic and antidromic responses.
AB  - The tolerance of electrical responses in the CA1 neurons of guinea pig
      hippocampal slices to elevated temperatures was studied by recording orthodromic
      and antidromic responses of the population spike (PS). Increasing the temperature
      of the perfusing medium from 30 degrees C to 49 degrees C resulted in a decreased
      amplitude of both the orthodromic and antidromic PS, the former disappearing at
      42.0 +/- 1.8 degrees C and the latter at 46.2 +/- 1.3 degrees C (n = 8 for both).
      When the temperature was increased to 44 degrees C, maintained at this level for
      less than 27 min, then lowered to 30 degrees C, both the orthodromic and
      antidromic PS recovered within 60 min. When the temperature was increased to 45
      49 degrees C, marked irreversible effects were seen with the orthodromic PS,
      recovery being dependent on the maximum temperature and duration of exposure, the
      change becoming irreversible after 13 min at 45 degrees C, 6 min at 46 degrees C,
      4 min at 47 degrees C or 2.5 min at 48 degrees C. In contrast, the antidromic PS,
      recorded simultaneously, recovered on lowering the temperature to 30 degrees C in
      all cases tested, except when the temperature was increased to 46 degrees C and
      maintained at this level for 25-27 min. These results indicate that, in CA1
      neurons, temperatures above 44 degrees C have more potent irreversible effects on
      synaptic transmission than on axonal or somal function.

PMID- 9589326
TI  - Intracellular distribution of hsp70 during long duration moderate hyperthermia.
AB  - Hyperthermia causes cell killing and is also an effective radiosensitizer. In
      recent years, the protocol of long duration moderate hyperthermia (LDMH) has been
      used to treat cancer patients in the clinic. However, the results of many studies
      indicate that some tumour cells may reveal the capability to express chronic
      thermotolerance, a factor of potentially critical impact in the efficacy of
      clinical hyperthermia. Previously it has been reported that two out of five human
      cell lines studied were able to proliferate at 41.1 degrees C. In the present
      study, the intracellular distribution of hsp70 during LDMH was measured as a
      potential marker for chronic thermotolerance with continued cell proliferation.
      In all cell lines studied, hsp70 became localized in the nucleus immediately
      after the cells were shifted from 37 degrees C to 41.1 degrees C. However, in the
      two cell lines which recovered and continued to proliferate, NSY42129 and HT29,
      hsp70 was delocalized from the nucleus within 4 h. Conversely, in the cell lines
      for which 41.1 degrees C was lethal, hsp70 did not delocalize from the nucleus
      but rather became localized in the nucleolar regions. Neither the NSY42129 cells
      nor the HT29 cells showed any preferential nucleolar punctate staining. Thus, it
      appears that the pattern of hsp70 nuclear localization and delocalization is
      related to the cells' ability to survive moderate heat shocks.

PMID- 9589327
TI  - Temporal association between alterations in proton extrusion and low pH
      adaptation.
AB  - Cells which have been adapted to growth at low extracellular pH (pHe) typically
      develop both an upregulation of steady state intracellular pH (pHi) and an
      ability to develop thermotolerance to 42 degrees C hyperthermia. These properties
      were acquired at different times, however. Days were required at pHe = 6.70 for
      two cell lines to adapt to low pHe by the thermotolerance criterion, but both had
      elevated steady state pHi values after only 4 hours at pHe = 6.70. A better
      correlation with adaptation to low pHe (as defined by hyperthermia) was found
      with changes in proton extrusion and the rate of pHi recovery after cytosolic
      acidification.

PMID- 9589328
TI  - [Diagnosis and therapy of stroke].

PMID- 9589329
TI  - [New trends in lipidology. Which patient benefits from cholesterol lowering
      therapy?].

PMID- 9589330
TI  - Sentinel events: approaches to error reduction and prevention.
AB  - Serious and undesirable events in health care organizations should trigger
      analysis and response to minimize the risk of recurrence. Sentinel Events:
      Evaluating Cause and Planning Improvement, a new book from the Joint Commission,
      describes the types of errors and sentinel events that have been reported in
      health care organizations, how organizations can respond to these events, how
      sentinel events are investigated through root cause analysis, and the Joint
      Commission's policy on sentinel events. Several case studies and examples
      demonstrate successful event investigation and improvement efforts in health care
      organizations. This excerpt addresses prevention of sentinel events through
      proactive, risk-reduction approaches. It is our hope that, even without the
      stimulus of a sentinel event, organizations will embrace the concept of
      prospective design and analysis of health care processes and systems to minimize
      the possibility of errors and to protect patients from the effects of errors that
      do occur.

PMID- 9589331
TI  - Cesarean section rates: effects of participation in a performance measurement
      project.
AB  - BACKGROUND: A decade-old indicator-based research initiative, Maryland's Quality
      Indicator (QI) Project, analyzed data for cesarean section rates among its
      approximately 1,100 voluntarily participating hospitals. It was posited that
      continuous participation in this performance measurement initiative would be
      associated with decreased primary and repeat C-section rates. METHODS: A
      retrospective study compared a group of 110 hospitals that reported on the C
      section indicator continuously between 1991 and 1996 with a group of hospitals
      that did not continuously report data on the C-section rate. RESULTS: Among the
      110 continuously participating hospitals in the QI Project, the total C-section
      rate declined from 22.5% in 1991 to 19.4% in 1996 (p < .01). For this same group,
      the primary C-section rate declined from 15.8% to 13.9% (p < .01), and the repeat
      C-section rate declined from 75.0% to 61.2% between 1991 and 1996 (p < .01). The
      comparison group of 957 hospitals that did not continuously participate in C
      section reporting between 1991 and 1996 did not experience a statistically
      significant difference in total C-section rates during this time (from 21.2% in
      1991 to 20.7% in 1996). In attempting to investigate alternative explanations for
      these results, a subsequent analysis of eight hospital variables potentially
      related to cesarean delivery rates found no significant differences between the
      two groups. CONCLUSIONS: This study provides support for the positive association
      between continuous participation in a performance measurement project and
      performance improvement.

PMID- 9589332
TI  - Asking residents about adverse events in a computer dialogue: how accurate are
      they?
AB  - BACKGROUND: Although retrospective identification of adverse events is time
      consuming, whether they are present and/or expected is often readily apparent to
      providers during the provision of care. METHODS: A computer program to flag
      admissions with possible adverse events was developed. Readmissions to the
      hospital within 31 days and admissions including more than one visit to the
      operating room (OR) were flagged. For surgical site infections, all admissions-
      including a visit to the OR--were flagged, but only a sample was evaluated in the
      reliability assessment. Residents in an urban, tertiary care hospital were
      questioned when inputting computerized discharge orders regarding adverse events
      among 391 cases sampled from 6,813 admissions for a two-month period. RESULTS:
      For the 228 readmissions (3.3% of all admissions) identified by the computer
      program, resident responses had a sensitivity of 57% and a specificity of 73% in
      detecting an unexpected readmission (nurse responses, 96% and 91%). For the 79
      patients with a return to the OR, the residents' responses had a sensitivity of
      86% and a specificity of 84% for detecting an unexpected return (versus 75% and
      98% for the nurses' responses). For the 209 patients with an OR visit, the
      sensitivity and specificity for a surgical site infection were 85% and 98% for
      the residents and 54% and 99% for the nurses. DISCUSSION: Information systems can
      be used to screen for adverse events and to ask providers whether adverse events
      are unexpected, although the reliability of this approach is likely to vary by
      event type.

PMID- 9589333
TI  - TQI in the Albuquerque Veterans Affairs Medical Center's long-term oxygen therapy
      program.
AB  - BACKGROUND: Long-term oxygen therapy (LTOT) is the only treatment demonstrated to
      prolong the life of patients with chronic obstructive pulmonary disease. In
      November 1994, a multidisciplinary total quality improvement (TQI) team composed
      of the involved hospital services was established to reorganize and improve the
      LTOT program at the Albuquerque Veterans Affairs Medical Center (AVAMC),
      Albuquerque. FROM THE OLD TO THE NEW PROCESS: The LTOT team used a process map to
      analyze the current process and gather information from patients and staff
      regarding their satisfaction with the program. It then began working on the
      identified problems and streamlining the LTOT referral process. A respiratory
      therapy position with the specific responsibility of serving as the home oxygen
      (O2) coordinator (HOC) was established and filled. The evaluation process was to
      be initiated by the AVAMC physicians, following which the HOC would perform a
      newly standardized evaluation that would establish the patient's need for O2 and
      result in a specific prescription. RESULTS: Quality indicators were selected to
      monitor changes in the program. Data from chart reviews, the Veterans Affairs
      National Cost Containment Center, and patient surveys were used to evaluate the
      indicators. Timeliness of referral to the program before inpatient discharge
      improved, O2 prescriptions in the new program more frequently addressed activity,
      and the cost per patient was reduced by 37.1%. Patient satisfaction rates also
      improved. DISCUSSION: A motivated team with representatives of the services
      involved was able to analyze and dramatically improve an important but
      complicated program.

PMID- 9589334
TI  - Managed care ethics: oxymoron or opportunity?. Interview by Louise Kaegi.

PMID- 9589335
TI  - Parental permission in adolescent health research.

PMID- 9589336
TI  - Incarcerated adolescents in Washington state. Health services and utilization.
AB  - This study describes the health services for incarcerated adolescents in
      Washington State and their utilization, in 12 juvenile detention facilities
      statewide, including six state (long-term, postadjudication) and six county
      (short-term, preadjudication) facilities. Findings differed by facility type,
      with youth at county facilities having more total visits to emergency rooms and
      more health care visits per inmate for health problems presenting acutely, such
      as sexually transmitted disease, pregnancy, urologic problems, and trauma. More
      were on suicide watch and on psychiatric medication. Health care used by youth at
      state facilities tended to be for more chronic conditions such as dental,
      dermatologic, nutritional, and respiratory problems. When utilization was
      analyzed by size of facility, small facilities had fewer health care visits and
      fewer nursing hours per inmate. According to our findings, there are at least 14
      pregnant adolescents and 2 HIV-infected adolescents incarcerated in this state at
      any time.

PMID- 9589337
TI  - Healthy youth development as a model for youth health promotion. A review.

PMID- 9589338
TI  - School importance and dropout among pregnant adolescents.
AB  - PURPOSE: This study examined the relationship of psychological well-being, social
      support, and demographic variables to school importance and school dropout among
      pregnant teens. METHOD: Fifty-one Caucasians and 68 African-Americans (mean age =
      16.7 years, mean weeks pregnant = 23) were recruited from two Baltimore area
      prenatal teen clinics. The adolescents completed questionnaires measuring
      depression, self-esteem, mastery, parental and friend support, demographic
      characteristics (i.e., age, marital status, ethnicity, socioeconomic status),
      school importance, and status. RESULTS: Most adolescents were enrolled in school
      or had graduated (69.7%), were receiving at least passing grades (78.7%), and
      perceived finishing high school as very important (76.7%). Blacks were more
      likely to say school was important (p < 0.001), were less likely to drop out (p <
      0.01), and received higher grades (p < 0.01) than whites. Dropouts had lower
      family incomes than current school attenders and graduates (p < 0.05). One
      measure of psychological well-being (mastery, p < 0.01) was positively correlated
      with school importance. Social support did not correlate with school importance
      or dropout. CONCLUSIONS: These findings suggest that dropping out of school among
      pregnant teens may be more strongly related to sociocultural factors than to
      individual characteristics such as emotional support and psychological well
      being. Overall, this study reveals a positive picture of educational continuation
      and performance during pregnancy, with most adolescents recognizing the
      importance of education and remaining in school.

PMID- 9589339
TI  - Experience of violence among teenage mothers in Alaska.
AB  - PURPOSE: To quantify the experience of violence before, during, and after
      pregnancy among teenage mothers compared to older mothers and to identify the
      proportion of births to teenagers that result from statutory rape. METHODS: We
      analyzed data collected during 1991-1994 from the Alaska Pregnancy Risk
      Assessment Monitoring System (PRAMS), a population-based, stratified sample
      survey of 200 of the approximately 900 Alaska resident women each month who have
      delivered a live infant. RESULTS: Compared to new mothers at least 20 years of
      age, mothers < 18 and 18-19 years of age were approximately twice as likely to
      report having experienced violence during pregnancy (10% vs. 4%) and were two to
      three times as likely to have experienced violence after pregnancy (10% and 6%,
      respectively, vs. 3%). When controlling for potentially confounding factors,
      however, age was associated with the experience of violence only for mothers < 18
      years after pregnancy. The percentage of women who reported experiencing violence
      each week increased following pregnancy for mothers of all ages. At least 38.9%
      and up to 66.2% of all births to unmarried teenagers younger than 16 years of age
      resulted from second-degree statutory rape. CONCLUSIONS: Teenage mothers are more
      likely to experience violence during and after their pregnancy than older women
      and for women of all ages the risk increases after pregnancy. Nearly half of the
      births to the youngest teenagers result from second-degree statutory rape.

PMID- 9589340
TI  - Are there risk factors for hepatitis B infection in inner-city adolescents that
      justify prevaccination screening?
AB  - PURPOSE: This study was undertaken to determine if homelessness could serve as a
      marker for previous hepatitis B infection (HBI), and thus justify prevaccination
      screening. METHODS: One hundred sexually active 13-21-year-olds (mean = 17
      years), 74% female, attending an inner-city hospital-based adolescent clinic
      (HOSP), and 48 sexually active 13-21-year-olds (mean = 19 years), 40% female,
      attending a clinic based at an urban drop-in center (UDC) for street youth were
      consecutively enrolled, screened for HBI serum markers and administered a
      structured interview about sexual practices, sexual abuse, prior sexually
      transmitted diseases (STDs), and injection drug use. RESULTS: For the HOSP group,
      7% were homeless and 4% were HBI positive. In the UDC group, 96% were homeless
      and 23% were HBI positive. Homelessness was significantly associated with HBI (p
      < 0.001), and this was corroborated by logistic regression analysis (p < 0.01).
      Other factors significantly associated with HBI in adolescents included a history
      of anal sex (p < or = 0.002), anal-receptive sex (p < or = 0.01), genital
      Chlamydia (p < or = 0.03), prostitution (p < or = 0.03), and sexual abuse (p < or
      = 0.002). For both populations, gender, sexual orientation, intravenous drug use,
      and genital sex were not related to HBI. CONCLUSION: These data indicate that
      homelessness and associated high-risk sexual practices may be indications for
      prevaccination screening for HBI in adolescents.

PMID- 9589342
TI  - Premenstrual symptoms. Prevalence and severity in an adolescent sample.
AB  - PURPOSE: To survey the prevalence and severity of premenstrual symptoms and
      compare premenstrual symptom clusters of younger (13-15-year-old) and older (16
      18-year-old) adolescents, based on both chronological and gynecological age.
      METHODS: Physical, emotional, and behavioral premenstrual symptoms were assessed
      by self-report using the Premenstrual Assessment Form (PAF), in a sample of 75
      adolescents. Analyses were performed to determine differences in premenstrual
      symptom clusters in younger and older adolescents. RESULTS: The participants had
      a mean age of 14.8; 96% identified themselves as Caucasian, 3% as African
      American, and 1% as Asian. All participants reported at least one premenstrual
      symptom of minimal severity. Many reported symptoms that they considered moderate
      (88%), severe (73%), or extreme (56%). The symptoms most commonly reported were
      food cravings, breast swelling, abdominal discomfort, mood swings, stressed
      feeling, and dissatisfaction with appearance. Other symptoms, such as missing
      time at school, becoming violent with people or things, and "thinking of what it
      would be like to do something to self" (such as crash the car), wishing to go to
      sleep and not wake up, or having thoughts of death or suicide, were less
      frequently reported. The younger teens (13-15 years old) had significantly less
      intense symptoms than the older teens (16-18 years old). CONCLUSIONS:
      Premenstrual symptoms reported as being moderate or greater in severity were
      found to be quite prevalent (88%) in this sample of adolescents. Specifically
      those adolescents at 41 months postmenarche or greater reported specifically more
      intense premenstrual symptoms. In addition, a subset of adolescents expressed
      that they experienced aberrant behavior and passive suicidal ideations as
      premenstrual symptoms.

PMID- 9589341
TI  - Changes in physical activity beliefs and behaviors of boys and girls across the
      transition to junior high school.
AB  - PURPOSE: This longitudinal study investigated gender-specific changes in physical
      activity beliefs and behaviors across the elementary to junior high school
      transition. METHODS: Physical activity beliefs and behaviors were measured in a
      cohort of 132 racially diverse youth during the year prior to and following the
      transition. Questionnaires assessed variables hypothetically linked to activity.
      Physical activity was monitored with the Child/Adolescent Activity Log. RESULTS:
      Gender differences in physical activity beliefs emerged. Across the transition,
      boys reported decreased efficacy, social support, and expectations (norms) to be
      physically active. Although girls also reported decreased social support for
      physical activity, they further reported exposure to fewer active role models and
      were less likely to perceive that the benefits of regular activity out-weighed
      the barriers following the transition. Gender differences in activity levels were
      apparent, with girls being less active than boys. Despite changes in physical
      activity beliefs across the school transition, no significant changes in actual
      level of activity occurred over this period. Although beliefs were significantly
      related to behaviors in the domain of physical activity, pretransition activity
      level was the best predictor of posttransition activity level. CONCLUSIONS: These
      data indicate that physical activity beliefs of adolescents change over the
      school transition. These changes are significantly, but not highly, related to
      level of physical activity. Future research should explore the influences of
      activity-related affect and social and physical contexts on physical activity
      across adolescence.

PMID- 9589343
TI  - Adolescents' insight in heavy drinking.
AB  - PURPOSE: Because so few adolescents with alcohol problems seek treatment, this
      study examined the factors associated with adolescents' recognition or insight
      into having a substance use problem. METHOD: Data were extracted from a self
      report questionnaire used in an epidemiological study of public middle school
      students on substance abuse in Arkansas. Those drinking heavily were divided into
      "admitters" and "deniers" based on their response to the question of having a
      substance use problem. Odds ratios were calculated to measure the association of
      several variables with admitting a problem. RESULTS: Of 3395 adolescents, 13.4%
      (455) met or exceeded our threshold for heavy drinking. Only 15.9% (65) of these
      heavy drinkers acknowledged having a substance use problem. Reporting more types
      of negative social events related to alcohol use and scoring higher on a measure
      of positive alcohol expectancies were significantly related to admitting to a
      substance use problem. Recent health care contact and perceived environmental
      factors did not independently contribute to insight. CONCLUSIONS: If these
      results are generalizable, treatment and educational interventions should
      emphasize linking alcohol use and negative social consequences.

PMID- 9589344
TI  - Factors associated with recent and discontinued alcohol use by pregnant
      adolescents.
AB  - PURPOSE: To determine easily identifiable risk factors that differentiate
      pregnant adolescents who report recent (past 30 days) alcohol use and those who
      discontinue use by their first prenatal visit from those who deny consuming
      alcohol altogether. METHODS: A structured interview was completed by 378
      adolescents < or = 17 years of age as part of standard care at our institution's
      adolescent obstetric clinic between July 7, 1992, and December 28, 1994. Using
      Chi-square or Student's t-tests, unique risk factors associated with recent or
      discontinued alcohol use in pregnancy were separately identified by comparing
      demographic, reproductive, behavioral, and environmental factors among recent
      users (n = 43), discontinued users (n = 48), and adolescents who denied ever
      using alcohol (n = 108). Significant indicators were then entered into stepwise
      logistic regression analyses to determine the most efficient models for
      predicting alcohol use. RESULTS: Partner alcohol use and use of alcohol during
      sexual activities were important risk factors for alcohol use by pregnant
      adolescents. Recent alcohol users were also more likely to be Mexican-American,
      to have quit school, and to report recent tobacco use, while adolescents who
      stopped using alcohol during pregnancy were significantly more likely to have
      witnessed or been a victim of or known a victim of violence. CONCLUSIONS:
      Screening at the first prenatal visit for these unique and easily assessed
      factors will help clinicians identify adolescents at greatest risk for alcohol
      use during pregnancy.

PMID- 9589345
TI  - A 5-year follow-up study of suicide attempts among French adolescents.
AB  - PURPOSE: The social, medical, and psychological outcomes of 552 adolescents
      hospitalized subsequent to an attempted suicide were assessed after an average 5
      year follow-up period. METHODS: Evaluation took place by means of mailed
      questionnaires completed by the adolescents, their parents, and the general
      practitioner. Using regression analysis, responses were compared with those of a
      comparison group (n = 273). RESULTS: In the suicidal group, the mean annual
      mortality rate was seven-fold greater than in the general population of the same
      age. Education level was lower, and the consumption of alcohol, psychiatric
      hospitalizations, and contacts with the criminal justice system were more
      frequent than in the control group. No other variables explored were
      significantly different between the two groups. CONCLUSIONS: The results of this
      study carried out on a large sample of French suicidal adolescents tend to
      confirm results of previous studies performed in other countries. They show that
      the prognosis for the suicidal adolescent group is less favorable than that of
      the comparison group.

PMID- 9589346
TI  - Properties of intraepithelial neoplasia relevant to the development of cancer
      chemopreventive agents.
AB  - Cancer chemoprevention is concerned with the development of drugs or diet
      supplements that will avert the onset or stop the progression of the
      intraepithelial neoplasia which precedes invasive cancer. Two basic processes
      underlie the onset and development of intraepithelial neoplasia. First is genomic
      instability (often associated with chronic diffuse epithelial hyperplasia), which
      is the increased production of genomic structural variants due to unrepaired DNA
      breaks with secondary formation of abnormal structures, including "mutator"
      mutations in genes responsible for genomic stability, gene copy amplification or
      loss from DNA breakage-fusion-anaphase bridge cycles, unequal sister chromatid
      exchange, and accumulation of double minutes. Second is the development within an
      epithelium having genomic instability of multicentric neoplastic lesions that
      independently progress through each of the following processes at a continuously
      accelerating rate: clonal evolution, hyperproliferation, production of genomic
      structural variants, and apoptosis. Recommended chemoprevention strategies based
      on these mechanisms are (1) early diagnosis and treatment of genomic instability
      before the appearance of intraepithelial neoplasia, i.e., during the
      "predysplastic" or "premorphologic" phase, (2) development of multiple agents
      that block intralesional proliferation at steps along the "command" pathways of
      mitotic signal transduction and along the "execute" pathways of synthesis of
      daughter cell components, (3) development of nontoxic antiinflammatory agents,
      antioxidants, antimutagens, and proapoptotics, (4) avoidance of "clonal escape"
      through use of drug combinations, and (5) use of computer-assisted quantitative
      image analysis to assay modulation of surrogate endpoints in chemoprevention
      clinical trials.

PMID- 9589347
TI  - Quantitation of preinvasive neoplastic progression in animal models of chemical
      carcinogenesis.
AB  - An assay method that precisely quantitates the cellular and tissue changes
      associated with early, preinvasive neoplasia is much needed as a surrogate
      endpoint biomarker (SEB) in clinical trials to predict the potential efficacy of
      chemopreventive agents in bringing about cancer incidence reduction.
      Quantification of histological changes at the tissue level are potentially
      powerful SEB's since these visually apparent changes are common in all neoplastic
      development, regardless of tissue type or neoplastic cause. Currently, subjective
      inspection of the histological appearance of sectioned and stained material, or
      "grading," by experienced pathologists is used to evaluate neoplastic
      progression. This has well-known limitations of reproducibility, accuracy, and
      resolution of grading scale. Since neoplastic changes are visually apparent and
      morphologic in nature, quantification by image analysis is a measurement modality
      of choice. Image analysis was implemented through the use of high-resolution
      "tiled" images of complete tissue sections. A histological grading system, or
      "scale," was developed that could be expressed in terms of normal deviate units
      of multiple and different morphometric descriptors. Neoplastic growth was
      characterized quantitatively with multiple measurements on each tissue image
      tile, which were combined into a single number for each tile, i.e., a histologic
      grade per tile, and parameters from the distributions of these measurements were
      used to represent the histologic grade for the entire region considered. This
      concept provided a uniform final scale in similar units of measurement,
      regardless of which tissues were graded. Also, the grading scale automatically
      adjusted measurement variance for different tissues by using normal tissue for
      each different type to obtain the normalization to standard deviation (z) units.
      This further defined a uniform final scale and maintained standard references.
      Using this method, results from two well-known animal models of carcinogenesis,
      squamous cell carcinoma of SENCAR mouse skin induced by benzo(a)pyrene (B[a]P),
      and squamous cell carcinoma of the rat esophagus induced by N
      nitrosomethylbenzylamine (NMBA), were compared to each other. Image analysis was
      performed on skin tissue sections from a total of 64 SENCAR mice, and esophagus
      tissue sections from 96 Fischer-344 rats. In both cases, a quantitative
      expression of the preinvasive neoplastic response to the carcinogen as a function
      of time of exposure was expressed along a continuous grading scale in standard
      deviation units (z). In the SENCAR mouse skin animal model, similar cohorts of 4
      mice at 20 weeks showed significant modulation of B[a]P-induced neoplasia by
      treatment with the antiproliferative agent difluoromethylornithine, P < .05. In
      the rat esophagus animal model, similar cohorts of 6 rats at 10 and 15 weeks
      showed significant modulation of NMBA-induced neoplasia by treatment with the
      antimutagen phenethyl isothiocyanate, P < .05.

PMID- 9589348
TI  - Suppression of protein kinase C and nuclear oncogene expression as possible
      molecular mechanisms of cancer chemoprevention by apigenin and curcumin.
AB  - Apigenin, a less-toxic and non-mutagenic flavonoid, suppressed 12-0-tetradecanoyl
      phorbol-13-acetate-(TPA)-mediated tumor promotion of mouse skin. TPA had the
      ability to activate protein kinase C (PKC) and induced nuclear proto-oncogene
      expression. Our study indicates that apigenin inhibited PKC by competing with
      adenosine triphosphate (ATP). Apigenin also reduced the level of TPA-stimulated
      phosphorylation of cellular proteins and inhibited TPA-induced c-jun and c-fos
      expression. Curcumin, a dietary pigment phytopolyphenol, is also a potent
      inhibitor of tumor promotion induced by TPA in mouse skin. When mouse fibroblast
      cells were treated with TPA alone, PKC translocated from the cytosolic fraction
      to the particulate fraction. Treatment with 15 or 20 microM curcumin for 15 min
      inhibited TPA-induced PKC activity in the particulate fraction by 26-60%.
      Curcumin also inhibited PKC activity in vitro by competing with
      phosphatidylserine. Curcumin (10 microM) suppressed the expression of c-jun in
      TPA-treated cells. Fifteen flavonoids were examined for their effects on
      morphological changes in soft agar and cellular growth in v-H-ras transformed
      NIH3T3 cells. The results demonstrated that only apigenin, kaempferol, and
      genistein exhibited the reverting effect on the transformed morphology of these
      cells. Based on these findings, it is suggested that the suppression of PKC
      activity and nuclear oncogene expression might contribute to the molecular
      mechanisms of inhibition of TPA-induced tumor promotion by apigenin and curcumin.

PMID- 9589349
TI  - Genetic alterations in mouse lung tumors: implications for cancer
      chemoprevention.
AB  - Specific genetic alterations affecting known tumor suppressor genes and proto
      oncogenes occur during mouse lung tumorigenesis. These include mutational
      activation of the K-ras gene, commonly seen at a frequency of about 80% in both
      spontaneously occurring and chemically induced adenomas and adenocarcinomas of
      the lung, suggesting that it is an early event that persists into malignancy.
      Allelic loss of the p16 tumor suppressor gene also is a frequent event, occurring
      in about 50% of mouse lung adenocarcinomas, but rarely in lung adenomas,
      suggesting that it may play a role in malignant conversion or progression of lung
      tumors. Other genetic alterations detected in mouse lung tumors include reduced
      expression of Rb and p16, and increased c-myc expression. Alterations of these
      genes are also common in the genesis of human lung cancer. Genetic linkage
      analysis to identify human lung cancer susceptibility genes is difficult due to
      the genetic heterogeneity and exposure to environmental risk factors. The mouse
      lung tumor model has become a valuable alternative for identifying such genes.
      Recently, loci responsible for mouse lung tumor susceptibility have been mapped
      to chromosomes 6, 9, 17, and 19, while those linked to lung tumor resistance have
      been mapped to chromosomes 4, 11, 12, and 18. Known candidate susceptibility or
      resistance genes include the K-ras proto-oncogene on chromosome 6, and the p16
      tumor suppressor gene on chromosome 4. With evidence of considerable overlap
      between the genetic alterations that underlie human and mouse lung tumorigenesis,
      the mouse lung tumor model has been expanded to include pre-clinical screening of
      chemopreventive agents against human lung cancer. Studies on the modulation of
      genetic defects in mouse lung tumors by known and potential chemopreventive
      agents should further the goal of developing an effective prevention and
      treatment of lung cancer.

PMID- 9589350
TI  - Genetic markers for early detection of lung cancer and outcome measures for
      response to chemoprevention.
AB  - Lung cancer is one of the leading causes of cancer death in the world. The high
      mortality rate for lung cancer probably results, at least in part, from the
      absence of standard clinical procedures for diagnosis of the disease at early and
      more treatable stages compared to breast, prostate, and colon cancers. The
      delineation of genetic alterations that occur in lung tumorigenesis may aid in
      both developing molecular markers for early detection and predicting of response
      to chemoprevention/chemotherapy. Cytogenetic and molecular genetic studies have
      shown that mutations in protooncogenes and tumor suppressor genes (TSGs) are
      critical in the multi-step development and progression of lung tumors.
      Inactivation of TSGs are by far the most common mutational events documented
      during the development of lung cancer. For example, loss of function of the Rb
      and/or p53 genes has been detected in both small cell lung cancer (SCLC) and non
      small cell lung cancer (NSCLC). In addition, allelic loss analyses have
      implicated the existence of other tumor suppressor gene loci on 9p as well as on
      3p, 5q, 8p, 9q, 11q, 11q, and 17q. We examined the short arm of chromosomes 3 and
      9 for TSG loci by analyzing 23 squamous cell carcinomas of the lung with numerous
      microsatellite markers. On chromosome 9p, loss of heterozygosity was detected in
      all of the 23 tumors and homozygous deletions of the p16/CDKN2 locus were
      detected in 6 of the 23 (26%) tumors. In addition, a novel region of homozygous
      deletion was detected in 6 of the tumors (26%) at D9S126. The homozygous deletion
      of D9S126 was confirmed by fluorescent in situ hybridization (FISH) analysis of
      tumor tissue touch preparations and isolated nuclei using P1 and cosmid probes
      that contain D9S126. Only one tumor harbored a homozygous deletion at both the
      p16/CDKN2 locus and the D9S126 locus. The data identify a region of homozygous
      loss on the short arm of chromosome 9, suggesting the presence of a novel TSG
      locus approximately 2.5 cM proximal to p16/CDKN2. On chromosome 3p, a similar
      high percentage of the tumors exhibited loss of heterozygosity. Also, homozygous
      deletions were detected in several tumors at 3p21.3. Thus, FISH analysis with
      probes containing the D9S126 or p16 locus could be used as molecular markers to
      assay sputum samples for premalignant cells exfoliated from the bronchial
      epithelium. Probes from other chromosome regions such as 3p21 could be used in a
      similar manner.

PMID- 9589351
TI  - Molecular cytogenetic alterations in the early stage at human bronchial
      epithelial cell carcinogenesis.
AB  - Lung carcinogenesis is a multi-step process involving activation of oncogenes and
      inactivation of tumor suppress genes. Many molecular and cytogenetic alterations
      occur in the early stages of carcinogenesis. We have developed an effective
      culture system for human bronchial epithelial cells and lung cancer cells. Four
      immortalized human bronchial epithelial cell lines were established by
      transfecting the epithelial cells with plasmid DNA containing the early region of
      SV40. Some molecular and cytogenetic alterations, such as 3p-, 2q-, 9p-, c-myc
      translocation t(8;14) (q23; q32), were found in one immortalized bronchial
      epithelial cell line M when approaching malignant transformation. An increase in
      cell proliferation and decrease of apoptosis were noted in the late passages of
      the immortalized cell line M. Some molecular cytogenetic alterations were also
      observed in human primary non-small cell lung cancers. Molecular cytogenetic
      alterations during the early stage of carcinogenesis of human bronchial
      epithelial cells may be useful as biomarkers for both diagnosis and intermediate
      endpoint of chemoprevention of lung cancer.

PMID- 9589352
TI  - Chemopreventive effect of difluoromethylornithine (DFMO) on mouse skin squamous
      cell carcinomas induced by benzo(a)pyrene.
AB  - The effect of the chemopreventive agent D,L-alpha-difluoromethylornithine (DFMO)
      on the incidence of skin squamous cell carcinoma was studied in SENCAR mice
      treated weekly with topical applications of benzo(a)pyrene (B(a)P) (0.15 mmol, 2
      x /week) on the dorsal skin. Animals were randomized to receive either chow or
      chow supplemented with DFMO (1 g/1 kg) and studied at 10, 15, 20, 25, and 30
      weeks of B(a)P treatment. Morphometric analyses at each timepoint evaluated the
      epidermal thickness (ET) and the number of epidermal nucleated layers (NL). The
      ET increased from 12-17 microns as early as 10 weeks after B(a)P treatment,
      reaching 22 microns at 20 weeks, and 27 microns at 25 weeks (130% increase). The
      NL also increased markedly. A relatively modest increase in ET was observed in
      animals treated with B(a)P and DFMO (16% at 15 weeks, 53% at 20 weeks, and 85% at
      25 weeks) as compared to controls. The relative increase in NL showed a similar
      pattern. Although extensive epidermal hyperplasia was seen early, clear-cut focal
      premalignant lesions were not identifiable before week 20 of B(a)P treatment. At
      20 weeks, the most frequently noted focal premalignant lesions in carcinogen
      treated animals (without DFMO) were moderate dysplasias. At 25 and 30 weeks, a
      large increase was seen in the incidence of more advanced dysplastic lesions and
      invasive carcinomas. In the group treated with B(a)P and DFMO, a marked reduction
      in the number of carcinomas was observed at 25 and 30 weeks. At 25 weeks, DFMO
      reduced tumor yield from 5.8 to 3.2 carcinomas per mouse. At 30 weeks, the
      reduction was from 13.1 to 5.7 carcinomas per mouse (57% reduction).
      Collectively, these data emphasize the strong chemopreventive effect of DFMO
      against tumors in the mouse skin complete carcinogenesis model, as indicated by
      the reduction of overall skin tumor incidence and the decreased epidermal
      hyperplasia in DFMO-treated animals. Morphometrically defined increases in ET and
      NL can be used as early biomarkers of DFMO chemoprevention in mouse skin
      tumorigenesis.

PMID- 9589353
TI  - Genes differentially expressed with malignant transformation and metastatic tumor
      progression of murine squamous cell carcinoma.
AB  - Molecular changes occurring with tumor formation and metastasis need to be
      identified in order to define novel markers and targets for chemoprevention and
      therapy. Cell lines from a multistage model of murine squamous cell carcinoma
      were analyzed for differences in gene expression using mRNA differential display.
      mRNA was isolated from primary keratinocytes, an in vitro transformed
      keratinocyte line (Pam 212), and three metastatic cell lines derived from Pam 212
      following tumor progression in vivo. cDNA was synthesized by reverse
      transcription and amplified by PCR using 72 primer combinations to screen and
      compare approximately 3,600 sequences. Five cDNAs with a differential expression
      pattern confirmed by Northern blot analysis were cloned and sequenced, revealing
      homology with known genes. The gene encoding tropomyosin alpha was preferentially
      expressed in primary keratinocytes; genes for tyrosine kinase Yes-associated
      protein (YAP65) and ribosomal protein L18a were preferentially expressed in
      transformed and metastatic tumor cell lines; and genes for the Gro-alpha family
      cytokine KC and antigen Sp17 exhibited increased expression in the three
      metastatic cell lines. The structure and function of the genes identified suggest
      that they may possibly be linked to cell shape and motility, signal transduction,
      protein synthesis, growth, granulocyte chemotaxis, and angiogenesis. This study
      demonstrates the ability of mRNA differential display to detect altered gene
      expression in this tumor progression model of murine squamous cell carcinoma, and
      the potential usefulness of this approach for identification of candidate genes
      as chemoprevention markers and targets.

PMID- 9589354
TI  - Breast cytology and biomarkers obtained by random fine needle aspiration: use in
      risk assessment and early chemoprevention trials.
AB  - In a prospective pilot study, we performed breast fine needle aspirations (FNAs)
      on 224 high-risk and 30 low-risk women and analyzed these aspirates for cytologic
      changes and biomarker abnormalities of aneuploidy and overexpressed estrogen
      receptor (ER), epidermal growth factor receptor (EGFR), p53 and HER-2/neu. High
      risk women had a first-degree relative with breast cancer (74%), prior biopsy
      indicating premalignant breast disease (25%), a history of breast cancer (13%),
      or some multiple of these risk factors (12%). Median ages of the high- and low
      risk groups were 44 and 42, respectively. Seventy percent of high-risk and 17% of
      low-risk women had cytologic evidence of hyperplasia with or without atypia (P <
      .0001). Aneuploidy and overexpression of EGFR and p53 occurred in 27, 37, and 29%
      of high-risk subjects but only 0, 3, and 3% of low-risk subjects (P < .0023).
      Overexpression of ER and HER-2/neu occurred in 7 and 20% of high-risk women but
      in none of the low-risk subjects. Biomarker abnormalities were more frequent with
      increasing cytologic abnormality. Restricting the analysis to those 3 biomarkers
      most frequently overexpressed in the high-risk group (ploidy, EGFR, p53), 13% of
      high-risk women with normal cytology, 19% of high-risk women with epithelial
      hyperplasia, and 49% of high-risk women with hyperplasia with atypia had
      abnormalities of 2 or more of these 3 biomarkers (P = .00004). At a median follow
      up of 32 months, four women have been diagnosed with invasive cancer and two with
      ductal carcinoma in situ (DCIS). Later detection of these neoplastic conditions
      was associated (P < or = .016) by univariate analysis with prior FNA evidence of
      hyperplasia with atypia; overexpression of p53 and EGFR; the modified Gail risk
      of breast cancer development at 10 years; and multiple biomarker abnormalities.
      By multivariate analysis, later detection of cancer was primarily predicted by
      the number of biomarker abnormalities in the 3-test battery (P = .0005) and
      secondarily by the Gail risk at 10 years (P = .0049). In turn, hyperplasia with
      atypia was associated with multiple biomarker abnormalities, particularly p53 and
      EGFR overexpression. Thus, hyperplasia with atypia and cytologic markers in
      breast FNAs have promise as risk predictors and as surrogate endpoint biomarkers
      for breast cancer chemoprevention trials.

PMID- 9589355
TI  - Dose-ranging study of indole-3-carbinol for breast cancer prevention.
AB  - Sixty women at increased risk for breast cancer were enrolled in a placebo
      controlled, double-blind dose-ranging chemoprevention study of indole-3-carbinol
      (I3C). Fifty-seven of these women with a mean age of 47 years (range 22-74)
      completed the study. Each woman took a placebo capsule or an I3C capsule daily
      for a total of 4 weeks; none of the women experienced any significant toxicity
      effects. The urinary estrogen metabolite ratio of 2-hydroxyestrone to 16 alpha
      hydroxyestrone, as determined by an ELISA assay, served as the surrogate endpoint
      biomarker (SEB). Perturbation in the levels of SEB from baseline was comparable
      among women in the control (C) group and the 50, 100, and 200 mg low-dose (LD)
      group. Similarly, it was comparable among women in the 300 and 400 mg high-dose
      (HD) group. Regression analysis showed that peak relative change of SEB for women
      in the HD group was significantly greater than that for women in the C and LD
      groups by an amount that was inversely related to baseline ratio; the difference
      at the median baseline ratio was 0.48 with 95% confidence interval (0.30, 0.67).
      No other factors, such as age and menopausal status, were found to be significant
      in the regression analysis. The results in this study suggest that I3C at a
      minimum effective dose schedule of 300 mg per day is a promising chemopreventive
      agent for breast cancer prevention. A larger study to validate these results and
      to identify an optimal effective dose schedule of I3C for long-term breast cancer
      chemoprevention will be necessary.

PMID- 9589356
TI  - Detection of differentially expressed genes in methylnitrosourea-induced rat
      mammary adenocarcinomas.
AB  - In this study, altered gene expression in five methylnitrosourea (MNU)-induced
      rat mammary adenocarcinomas was investigated using a newly developed competitive
      cDNA library screening assay. In order to detect the differentially expressed
      cDNA transcripts, three cDNA libraries (rat mammary, rat liver, and rat kidney)
      with over 18,000 clones were differentially screened with competing normal and
      neoplastic mammary cDNA probes. Ninety-eight clones indicated by competitive
      hybridization to be differentially expressed in tumors were verified by dot-blot
      hybridization analysis. Of these clones, 45 were found to be overexpressed while
      53 were underexpressed in tumors. Forty-five of the confirmed clones were further
      analyzed by single-pass cDNA sequence determination. Four clones showed homology
      with cytochrome oxidase subunit I, polyoma virus PTA noncoding region,
      cytoplasmic beta-actin, and mouse secretory protein containing thrombospondin
      motifs. Further investigation into the potential roles of these identified genes
      should contribute significantly to our understanding of the molecular
      mechanism(s) of rat mammary tumorigenesis.

PMID- 9589358
TI  - Effect of retinoic acid on HPV titration and colposcopic changes in Korean
      patients with dysplasia of the uterine cervix.
AB  - Retinoids, a family of molecules capable of profound impact on many biological
      functions, have antiproliferative, differentiative, and immunomodulatory
      properties. The present study assessed the effect of 13-cis-retinoic acid (13
      CRA) treatment in 13 chronic cervicitis and 52 cervical intraepithelial neoplasia
      patients. We examined low- and high-risk human papilloma virus titer (using the
      hybrid capture method) and made a colposcopic and cervicographic examination
      before and after treatment with 13-CRA at 1 mg/kg for 4 to 12 weeks. Patients
      were between 27 and 64 years, the average age being 36.6 years. Histology
      revealed chronic cervicitis in 13 cases, mild dysplasia in 18 cases, moderate
      dysplasia in 18 cases, and severe dysplasia in 16 cases, totaling 65 cases. The
      expression rate of high-risk human papilloma virus (HPV 16, 18) was 9 of 13 cases
      (69%) in chronic cervicitis, 7 of 18 cases (38%) in mild dysplasia, 9 of 18 cases
      (50%) in moderate dysplasia, and 12 of 16 cases (75%) in severe dysplasia, with
      the overall expression rate being 37 of 65 cases (57%). Following 13-CRA
      treatment, decreases in high-risk titer were observed in 6 of 9 cases (66%) of
      chronic cervicitis, 4 of 11 cases (36%) of mild dysplasia, 7 of 9 cases (77%) of
      moderate dysplasia, and 8 of 12 cases (75%) of severe dysplasia. Overall, HPV
      titer decreased in 25 of 41 cases (61%). Minimal changes were found in
      colposcopic and cervicographic observations during the study. In summary, high
      risk HPV titer decreased after treatment with 13-CRA in the majority of patients
      with cervical intraepithelial neoplasia. This study supports the potential of
      retinoids to interrupt multi-step carcinogenesis, possibly by down-regulation of
      gene products (E6,E7) produced by HPV infection.

PMID- 9589357
TI  - Polyamine measurements in the uterine cervix.
AB  - Cervical cancer remains a significant health problem. New strategies based on the
      molecular aspects of cervical carcinogenesis are needed. Chemoprevention
      represents a novel strategy for cervical cancer prevention. Our group plans phase
      I and II trials using alpha-difluoromethylornithine, a suicide inhibitor of
      ornithine decarboxylase and potent antiproliferative chemopreventive agent. We
      conducted a study to identify which polyamines in tissue could best serve as
      surrogate endpoint biomarkers for future trials. Thirty patients with biopsy
      proven cervical intraepithelial neoplasia grade 3 underwent colposcopically
      directed biopsies of normal and abnormal areas of the uterine cervix for analysis
      of polyamine synthesis biomarkers. Statistically significant differences were
      found in the ornithine decarboxylase value and the spermidine:spermine ratio
      between normal and abnormal areas of the cervix. In general, the ranges in
      measurements varied widely. Differences in polyamine synthesis biomarkers between
      colposcopically normal and abnormal areas can be demonstrated. However, studies
      using polyamine synthesis biomarkers in the cervix would require large numbers of
      patients to achieve significance.

PMID- 9589359
TI  - Chemoprevention of cancer of uterine cervix: a study on chemoprevention of
      retinamide II from cervical precancerous lesions.
AB  - Dysplasia of the uterine cervix is a recognized precancerous condition. Because
      of the observed ability of retinoids to suppress various cell lines in vitro, a
      number of clinical studies have examined the effect these agents have on cervical
      dysplasia, with the object of developing a means of chemoprevention of cervical
      malignancies in women at risk. Three cervical cancer chemoprevention trials with
      Retinamide II (RII) have been conducted at the Cancer Institute, Chinese Academy
      of Medical Sciences, Beijing, China. A pilot study used RII to intervene in cases
      of precancerous cervical dysplasia. Twenty-seven women with mild, moderate, or
      severe cervical dysplasia, pathologically confirmed, were treated by RII
      suppositories, 10 mg QD, given intravaginally for 6 months (each course lasting 3
      months). The results indicated that after the second course, the overall response
      rate was 96.29% and the complete response rate was 88.89%. In general, side
      effects were mild. A little cervical and vaginal irritation was well tolerated.
      In the second double-blind study, patients with precancerous cervical lesions
      were randomized into two groups, one treated with RII suppository intravaginally
      and the other with a placebo, once daily for 50 days in two courses. Precancerous
      lesions in 68.76% of patients in the treatment arm disappeared, with an overall
      effective rate of 74.29% after two courses of treatment with RII. Its curative
      effect was approximately that of laser beam radiation and electrocautery (P >
      0.05), and differed significantly (P < 0.01) from that of traditional
      antiinflammatories. RII can be a major measure in prevention and treatment of
      cervical cancer in high-incidence areas in China. In the third trial, we are
      conducting a randomized double-blind study placebo controlled, in a high
      incidence area of cervical cancer (Xiang-Yuan county, Shang Xi Province, China).
      At present, the patients are being followed up and the study will be completed
      after 2 years.

PMID- 9589360
TI  - New rodent models for studies of chemopreventive agents.
AB  - Some recent studies of the effects of chemopreventive agents have begun to use
      new rodent models to improve the analysis of stages of colonic preneoplasia, and
      how chemopreventive agents modify progressive abnormal cell development. In one
      of the models of inherited predisposition to colon cancer, mice carrying a
      truncated Apc allele with a nonsense mutation in exon 15 have been generated by
      gene targeting and embryonic stem cell technology (Apc1638 mice). These mice
      develop multiple gastrointestinal lesions, including adenomas and carcinomas,
      focal areas of high-grade dysplasia (FAD), and polypoid hyperplasias with FADS.
      The incidence of inherited colonic neoplasms has now been modulated by a
      chemopreventive regimen. Colonic lesions significantly increased in Apc1638 mice
      on a Western-style diet, which has higher fat content and lower calcium and
      vitamin D compared to the same mice on AIN-76A diet. In another rodent model, Min
      mice were treated with sulindac, which markedly reduced the incidence of
      intestinal tumors. A third new rodent model containing a targeted mutation in the
      gene Mcc (mutated in colorectal cancer) recently became available for
      chemoprevention studies. These mice develop multiple types of neoplasms including
      adenocarcinomas, focal areas of gastrointestinal dysplasia, papillomas of the
      forestomach, and tumors in other organs including lung, liver, and lymphoid
      tissue. Feeding a Western-style diet to the Mcc mutant mice also resulted in
      significantly increased gastrointestinal lesions. These nutrient modifications
      also have been given to normal mice, demonstrating without any chemical
      carcinogen that a Western-style diet induced colonic tumorigenesis. Western-style
      diets also have now induced modulation of cell proliferation in other organs
      including mammary gland, pancreas, and prostate. These findings help develop new
      preclinical rodent models to aid the analysis of genetic and environmental
      factors leading to neoplasia, as well as new methods for evaluating the
      chemopreventive efficacy of specific nutrients and pharmacological agents.

PMID- 9589361
TI  - Colon cancer chemoprevention: clinical development of aspirin as a
      chemopreventive agent.
AB  - We have studied aspirin as a potential chemopreventive for colorectal cancer,
      completing Phase I studies on aspirin pharmacology and potential biomarker assays
      (prostaglandins, PGE2 and PGF2 alpha and cyclooxygenase modulation) in normal
      human subjects. These studies have determined the optimal dose of aspirin for
      future Phase IIa and IIb chemopreventive trials in high-risk cohorts of patients
      for colon cancer. Aspirin's effects on rectal prostaglandins are prolonged,
      detectable even after aspirin and its metabolite are removed from the plasma.
      Aspirin-mediated inhibition of prostaglandin production in the human rectal
      epithelium may be related to direct suppression of cyclooxygenase transcription
      and not to enzyme inactivation by acetylation. A systematic method to monitor
      adherence (self-report, telephone contact, pill count, and microelectronic
      monitoring) has been established for future trials. Strategies to improve
      recruitment of high-risk cohorts have been developed. Phase IIa non-randomized
      studies with aspirin at 81 mg in high-risk cohorts (resected Duke's A colon
      cancer, Duke's C colon cancer treated with adjuvant therapy and disease-free at 5
      years, history of colon adenomas > 1 cm, two or more first-degree relatives with
      colon cancer, and familial adenomatous polyposis and hereditary non-polyposis
      colorectal cancer syndromes) are currently being conducted for surrogate end
      point biomarker (prostaglandins, cyclooxygenase, cellular mucins, and
      proliferation) modulation.

PMID- 9589362
TI  - Esophageal and gastric cardia epithelial cell proliferation in northern Chinese
      subjects living in a high-incidence area.
AB  - Linxian and the nearby county Huixian, in the Henan province in Northern China,
      have a very high incidence of esophageal squamous cell carcinoma (SCC). Previous
      studies from these counties have suggested that increased proliferation of
      esophageal epithelial cells, morphologically manifested as basal cell hyperplasia
      (BCH) and dysplasia (DYS), is an early indicator of abnormality in persons
      predisposed to SCC. A high incidence of gastric cardia adenocarcinoma (AC) was
      also found in these areas. To determine proliferation patterns of esophageal and
      gastric cardia epithelia with normal and different severities of precancerous
      lesions, we measured proliferating cell nuclear antigen (PCNA), Ki-67, and
      bromodeoxyuridine (BrdU) incorporation and compared the results. Esophageal
      biopsies (175) and gastric cardia biopsies (41) were collected from symptom-free
      subjects in Huixian. Of these, 23 esophageal biopsies were incubated with BrdU.
      The avidin-biotin-peroxidase complex (ABC) method was used to detect PCNA, Ki-67,
      and BrdU. The number of immunostain-positive cells was counted manually. Intense
      immunostaining for PCNA, Ki-67, and BrdU was observed in the cell nuclei of
      tissues with normal and different severities of precancerous lesions. With
      esophageal biopsies, both PCNA and Ki-67 increased significantly as the epithelia
      progressed from normal to BCH and to DYS. The number of PCNA- and Ki-67-positive
      cells was three times higher than that of BrdU incorporation in the same category
      of BCH. With cardia biopsies, the number of Ki-67 positive cells was lower in
      normal tissue and increased significantly from chronic superficial gastritis to
      chronic atrophic gastritis to DYS. Staining patterns for PCNA and Ki-67 were
      correlated with the histopathology of the esophagus. The correlation was not as
      clear with gastric cardia. BrdU studies appear to be more complicated. The PCNA
      and Ki-67 methods may be useful for screening high-risk esophageal and gastric
      cardia cancer subjects, and for monitoring chemoprevention effects.

PMID- 9589364
TI  - Development of human prostate cancer models for chemoprevention and experimental
      therapeutics studies.
AB  - The progression of human prostate cancer from histomorphologic to clinical
      expression often requires several decades. This study emphasizes the importance
      of developing relevant human prostate cancer models to study the molecular events
      leading to prostate cancer progression. These models will provide a rational
      basis for chemopreventive and treatment strategies to retard the progression of
      human prostate cancer from its localized to its metastatic state. In our
      laboratory, we have established the LNCaP progression and ARCaP models and the in
      vitro three-dimensional growth models involving prostate cancer and bone stroma
      to study the progression of prostate cancer. We propose that prostate cancer may
      progress from an androgen-dependent to an androgen-independent state. While
      existing as androgen-independent tumors (defined as tumors capable of growing in
      castrated hosts and secreting PSA in serum), prostate cancer may assume three
      different phenotypes as it progresses: androgen-independent while remaining
      androgen-responsive; androgen-independent and unresponsive to androgen
      stimulation; and androgen-independent but suppressed by androgen. It is
      conceivable that any androgen-independent human prostate cancer may contain
      variable proportions of cells that exhibit these three phenotypes. This concept
      may have important implications in determining strategies for chemopreventive and
      therapeutic trials. We have established three-dimensional growth models of
      prostate cancer cells either in collagen gel or microgravity-simulated growth
      conditions to form viable and functional organoids which contain prostate cancer
      epithelial cells admixed with prostate or bone stromal cells. These in vitro
      models combined with the in vivo models described above will enhance our
      understanding of the regulatory mechanism of prostate cancer growth and
      progression, and hence could improve efficiency in screening chemopreventive and
      therapeutic agents which alter the biologic behaviors of human prostate cancer.

PMID- 9589365
TI  - Interracial comparative study of prostate cancer in the United States, China, and
      Japan.
AB  - The interracial differences of prostate cancer progression have long been
      documented; however, underlying molecular and cellular mechanisms remain obscure.
      This study focuses on the histopathologic, immunohistochemical, biochemical, and
      molecular characterization of prostate cancer tissues unselectively obtained from
      US, Chinese, and Japanese men. Histopathologic analyses indicate that 74.5% of
      the prostate cancers in Chinese patients were poorly differentiated, compared
      with 28.6 and 32.8% of the prostate cancers in US and Japanese men, respectively.
      These differences cannot be attributed to patient age, clinical stage of disease,
      or methods of tissue sampling. Furthermore, the high proportion of poorly
      differentiated prostate cancer tissues in the Chinese group was not related to
      the patients' access to medical service or their geographic origins within China.
      We found significantly higher levels of tumor angiogenesis (2- to 4-fold),
      serotonin (2- to 20-fold), and bombesin (7- to 16-fold), but not chromogranin A,
      in tissue specimens obtained from Chinese prostate cancer patients compared with
      those from US and Japanese patients. We also found marked differences in p53
      protein accumulation among various ethnic groups. The p53 protein was frequently
      detected in prostate cancer tissue specimens from Chinese (90.2%), but less
      frequently in US black (3.7%), US white (17.4%), and Japanese (7.1%) men. Further
      analysis of 31 prostate cancer tissues from Chinese men indicated that mutational
      changes in the p53 gene occurred between exons 5 and 8.

PMID- 9589363
TI  - Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of
      China.
AB  - Oltipraz has been used clinically in many regions of the world as an
      antischistosomal agent and is an effective inhibitor of aflatoxin
      hepatocarcinogenesis in rats. This chemopreventive action of oltipraz results
      primarily from an altered balance in aflatoxin metabolic activation and
      detoxication. In 1995, a randomized, placebo-controlled, double-blind
      intervention was conducted in residents of Qidong, People's Republic of China,
      who are at high risk for exposure to aflatoxin and development of hepatocellular
      carcinoma. The major study objectives were to define a dose and schedule for
      oltipraz that would reduce levels of aflatoxin biomarkers in biofluids of the
      participants, and to further characterize dose-limiting side effects. Two hundred
      thirty-four healthy eligible individuals, including those infected with HBV, were
      randomized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or
      placebo. Blood and urine specimens were collected to monitor potential toxicities
      and evaluate biomarkers over the 8-week intervention and subsequent 8-week follow
      up periods. Overall, compliance in the intervention was excellent; approximately
      85% of the participants completed the study. Objective evaluation of adverse
      events was greatly facilitated by inclusion of a placebo arm in the study design.
      A syndrome involving numbness, tingling, and pain in the fingertips was the only
      event that occurred more frequently among the active groups (18 and 14% of the
      daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%).
      These symptoms were reversible and could be relieved with non-steroidal
      antiinflammatory agents. A more complete understanding of the chemopreventive
      utility of oltipraz awaits completion of an assessment of the efficacy of
      oltipraz in modulating levels of aflatoxin biomarkers.

PMID- 9589366
TI  - Immediate-early gene expression in the brain of the thiamine-deficient rat.
AB  - Pyrithiamine-induced thiamine deficiency (PTD) in the rat is associated with
      neuronal loss in the thalamus and inferior colliculus. Recently, we were able to
      demonstrate the occurrence of apoptosis in the thalamus of these animals. Given
      that immediate-early genes (IEGs) participate in signal transduction pathways
      that mediate programmed cell death, the present study utilized in situ
      hybridization and immunohistochemistry to examine the expression of four IEGs (c
      fos, c-jun, fos-B, and NGFI-A) during the progression of PTD. Elevated c-fos mRNA
      levels were initially observed in the posterior medial thalamus on d 12 of the
      deficiency. At the acute symptomatic stage (characterized by a loss of righting
      reflex on d 16-17), the posterior-medial thalamus exhibited increased mRNA for
      all genes examined, whereas the inferior colliculus demonstrated mRNA induction
      for c-fos, c-jun, and NGFI-A. Immunohistochemical analysis revealed that
      elevations of IEG mRNA associated with the acute symptomatic stage were
      consistently translated into protein in the thalamus. In contrast, whereas
      elevated Fos- and Jun-like immunoreactivity were detected in the inferior
      colliculus at this stage, NGFI-A-like immunoreactivity declined significantly
      below basal levels, suggesting a translational block. These results are
      consistent with our recent findings of apoptotic cell death, and indicate that
      differential patterns of IEG expression occur in the thalamus and inferior
      colliculus during PTD, which may contribute to the pathogenesis of this disorder.

PMID- 9589368
TI  - Calcium mobilization and protease-activated receptor cleavage after thrombin
      stimulation in motor neurons.
AB  - Thrombin, the ultimate enzyme in the blood coagulation cascade, has prominent
      actions on various cells, including neurons. As in platelets, thrombin increases
      [Ca2+]i mobilization in neurons, and also retracts neurites. Both these effects
      are mediated through a G protein-coupled, proteolytically activated receptor for
      thrombin (PAR-1). Prolonged exposure to thrombin kills neurons via apoptosis,
      that may also involve PAR-1 activation. Increased [Ca2+]i has been a unifying
      mechanism proposed for cell death in several neurodegenerative diseases. Thrombin
      elevated calcium levels may activate intracellular cascades in neurons leading to
      cell death. Since thrombin mediates its diverse effects on cells through both
      heterotrimeric and monomeric G proteins, we also explored what effect altering
      differential G protein coupling would have on the neuronal response to thrombin.
      We studied calcium mobilization by thrombin in a model motor neuronal cell line,
      NSC19, using fluorescence image analysis. Confirming effects in other neuronal
      types, thrombin caused dramatic increases in [Ca2+]i levels, both transiently and
      after prolonged exposure, which involved activation and cleavage of the PAR-1
      receptor. Using enzyme linked immunosorbent assay (ELISA) and dot-blot analysis,
      we found that the N-terminal fragment of PAR-1 was released into the medium after
      exposure to thrombin. We confirmed that PAR-1 protein and mRNA expression
      occurred in motor neurons. We found that cholera toxin inhibited thrombin
      mediated Ca2+ influx, pertussis toxin did not significantly alter thrombin
      action, and lovastatin, a small 21-kDa Ras GTPase (Rho) modulator, showed a
      tendency to reduce the thrombin effect. These data indicate that thrombin
      increased [Ca2+]i, sufficient to trigger cell death in motor neurons, might be
      approached in vivo by modulating thrombin signaling through PAR-1.

PMID- 9589367
TI  - Expression and localization of muscarinic receptors in P19-derived neurons.
AB  - The muscarinic acetylcholine receptors are important in a variety of
      physiological processes such as induction of secretion from various glands and
      regulation of pacemaker activity, muscle tone, and neurotransmission. To date,
      the muscarinic receptor family includes five members (designated m1-m5), of which
      m1-m4 are abundant in brain and in peripheral tissues, and m5 is found
      exclusively in brain, and even there at very low levels. The expression of m1-m5
      receptor subtypes was studied in neurons derived from the murine embryonal
      carcinoma cell line P19. These cells serve as a model system for differentiation
      and maturation of neurons resembling CNS neurons. Our results show that P19
      neurons express mainly the m2, m3, and m5 subtypes. Low levels of m1 receptors
      are also detected and m4 subtype is practically absent. Furthermore, muscarinic
      receptors in P19 neurons are functional in activating second messenger signaling
      pathways. The localization of m2 receptors is predominantly presynaptic, whereas
      the m5 subtype is mainly postsynaptic. Consequently, P19 cells provide a model
      system for the study of pre- and postsynaptic muscarinic acetylcholine-receptor
      subtypes in a proper neuronal context. This is particularly valid for the rare m5
      receptors.

PMID- 9589369
TI  - Tyrosine hydroxylase and tryptophan hydroxylase do not form heterotetramers.
AB  - Tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) both contain a C
      terminal tetramerization domain composed of a leucine heptad repeat embedded
      within a 4,3-hydrophobic repeat. Previous mutagenesis experiments and X-ray
      crystallographic studies have demonstrated that these repeats are required for
      tetramer assembly of the hydroxylase enzymes via coiled-coil interactions. The
      specificity of these particular C-terminal intersubunit binding motifs was
      investigated by determining if TH and TPH can form heterotetramers when
      coexpressed in bacteria. Bacterial cells were contransformed with TH and TPH
      expression plasmids under kanamycin and ampicillin selection, respectively.
      Immunoprecipitation of induced bacterial supernatants with a TPH monoclonal
      antibody demonstrated that, unlike the human TH isoforms, TH and TPH do not form
      heterotetramers. The data suggest that specificity of oligomerization of the
      aromatic amino acid hydroxylases may be partially determined by polar amino acids
      interspersed within the coiled-coil. This finding should be influential in the
      development of eukaryotic expression systems and ultimately in gene therapy
      approaches.

PMID- 9589370
TI  - Substituted cGMP analogs can act as selective agonists of the rod photoreceptor
      cGMP-gated cation channel.
AB  - Cyclic nucleotide-gated (CNG) channels are expressed in many cell types in both
      the nervous system and nonexcitable tissues. In order to understand the roles of
      cGMP-gated channels, and to distinguish actions of cGMP mediated through CNG
      channels from those through cGMP-dependent protein kinase (G-kinase), several new
      cGMP analogs were tested for potency as CNG channel agonists. Using Xenopus
      oocytes expressing the rat rod cGMP-gated ion channel alpha-subunit, we showed
      that an analog containing a pCPT group at the 8-position, 8-pCPT-cGMP, was 80
      times more potent than cGMP and 14 times more potent than 8-Br-cGMP. 8-pCPT-cGMP
      is the most potent CNG channel agonist so far described and also has the
      advantages of much better membrane permeability as well as much higher resistance
      to PDE-hydrolysis, as compared with 8-Br-cGMP. Modification of both 8-Br-cGMP and
      8-pCPT-cGMP by introduction of a sulphur atom into the cyclic phosphate group
      gave smaller changes in agonist efficiency. Both Sp-8-Br-cGMPS and Sp-8-pCPT
      cGMPS acted as agonists of CNG channels and are also G-kinase activators. In
      contrast, Rp-8-Br-cGMPS was a channel agonist, with an EC50 of 173.5 microM, but
      a G-kinase antagonist with a Ki of 4 microM. Finally, Rp-8-pCPT-cGMPS was a
      channel agonist and showed additional noncompetitive antagonist activity at
      higher concentrations. The results suggest that 8-pCPT-cGMPS is a highly potent
      photoreceptor CNG channel agonist with high membrane permeability and PDE
      resistance and furthermore Rp-8-Br-cGMPS can be used to test whether the actions
      of cGMP are selectively mediated by CNG channels.

PMID- 9589371
TI  - Distribution of MnSOD polymorphisms in sporadic ALS patients.

PMID- 9589372
TI  - Isolation of a human-brain sodium-channel gene encoding two isoforms of the
      subtype III alpha-subunit.
AB  - Voltage-gated sodium channels are members of a multigene family of transmembrane
      proteins that are important determinants of electrical excitability in cell
      membranes. These proteins are typically composed of a large alpha-subunit and one
      or two beta-subunits. The primary structure of alpha-subunits is highly conserved
      among different subtypes and different species. Based on the conserved sequences
      and application of the rapid amplification of cDNA ends (RACE) reaction, we have
      isolated three overlapping clones from human brain. These sequences share highest
      homology (89%) to the rat brain subtype III gene and cover a 4.2-kb expanse of
      the transcript. The 5'-most clone has a translation start site located in the
      same region as other mammalian brain sodium channel genes. A 92-nucleotide insert
      was found in domain I at a location previously demarcated by published splice
      sites in rat brain sodium channels IIN/IIA and IIIN/IIIA. It is most likely that
      this transcript represents the two isoforms (neonatal and adult) of the human
      brain sodium channel gene, SCN3A (GenBank accession numbers AF035685 and
      AF035686). As is the case for rat brain sodium channels IIN/IIA and IIIN/IIIA,
      these isoforms are generated through an alternative splicing mechanism. The
      conservation of the exon structure suggests that alternative RNA splicing is a
      common feature for sodium channel mRNA processing and may play an important role
      in modulating the channel function.

PMID- 9589373
TI  - Endothelial cell dysfunction in preeclampsia.

PMID- 9589374
TI  - Predicting outcome in the idiopathic glomerulopathies.
AB  - Improving accuracy in predicting outcome in the idiopathic glomerulopathies
      requires standard clinical and laboratory data observed over time and the
      application of certain basic biostatistical tests. In our initial model we
      examined categories of glomerular disease that progress i.e. membranous,
      membranoproliferative, diffuse proliferative, focal sclerosing and IgA
      nephropathy. We determined that a combination of severity and persistence of
      proteinuria above certain levels over fixed time frames plus the knowledge of any
      change in glomerular filtration rate during these periods resulted in slopes of
      creatinine clearances that were the same across this histologic spectrum. This
      modeling of disease was then applied in a more rigorous fashion to our patients
      with idiopathic membranous nephropathy (IMGN). Multivariate logistic regression
      analyses was used to test all other potential clinical and laboratory predictors
      of chronic renal failure. These additional factors did not improve our ability to
      predict outcome. This algorithm was subsequently validated on two independent
      IMGN data bases. Overall accuracy of prediction estimated within 6 months of
      presentation was maintained at > 85%. The role of this type of evaluation in both
      clinical practice and research is discussed.

PMID- 9589376
TI  - Analgesic nephropathy and the use of nonsteroidal anti-inflammatory drugs in
      renal patients: new insight.
AB  - Analgesic-associated nephropathy due to analgesic mixtures and possibly due to
      nonsteroidal anti-inflammatory drugs taken over long periods of time represent a
      preventable cause of chronic renal failure. The exact prevalence of this
      condition in various countries around the world is still unclear almost 30 years
      after the original description of this entity. With the advent of specific
      diagnostic criteria, the prevalence should become much more clear by studying
      dialysis populations and other patients with chronic renal disease prior to end
      stage. The effect of analgesics and nonsteroidal drugs on renal disease of other
      established etiologies is not well-characterized either. Just as blood pressure
      control is essential in prolonging the course of chronic renal failure, the use
      of these NSAIDs may be a risk factor for accelerating such clinical courses. It
      is of interest that recent preliminary epidemiologic data suggest that prolonged
      and heavy use of illicit drugs can also be a risk factor for chronic renal
      disease (personal communication). Such risk factors are compatible with a public
      health approach towards prevention of a disease state in which expensive
      resources are necessary and for which the affected population is growing at
      alarming rates worldwide. Pharmaceutical manufacturers should be required to
      conduct properly controlled safety studies for long-term effects of compounds,
      particularly when they are to be released for over-the-counter consumption and
      are to be heavily marketed.

PMID- 9589375
TI  - Genotype-phenotype correlations in normotensive patients with primary renal
      tubular hypokalemic metabolic alkalosis.
AB  - Among the different forms of hereditary renal tubulopathies associated with
      hypokalemia, metabolic alkalosis and normotension, two main types of disorders
      have been identified: Gitelman disease, which appears to be a homogeneous post
      Henle's loop disorder, and Bartter syndrome, a heterogeneous Henle loop disorder.
      A specific gene has been found responsible for Gitelman disease, encoding the
      thiazide-sensitive Na-Cl cotransporter (TSC) of the distal convoluted tubule.
      From a phenotypic point of view the characteristic findings of this disease are
      hypocalciuria, hypomagnesemia and tetanic crises appearing during childhood or
      later. Many subjects are asymptomatic. At least three different genes have been
      shown to be responsible for Bartter syndrome, characterized by mutations in the
      proteins encoding respectively the bumetanide-sensitive Na-K-2Cl cotransporter,
      the inwardly-rectifying renal potassium channel and a renal chloride channel, all
      protein transports located in the ascending limb of Henle's loop. Mutations in
      the first two transport proteins have been demonstrated in patients with the
      hypercalciuric forms of Bartter syndrome associated with nephrocalcinosis
      (respectively Bartter syndrome type I and II), who were often born after
      pregnancies complicated by polyhydramnios and premature delivery. Mutations in
      the gene encoding a renal chloride channel were recently recognized in patients
      with a Henle tubular defect not associated with nephrocalcinosis (Bartter
      syndrome type III). Most of the latter group of patients were normo
      hypercalciuric and presented dehydration and life-threatening hypotension in the
      first year of life. However, these three genes do not explain all the patients
      with Bartter syndrome which unlike Gitelman disease, appears to be a very
      heterogeneous disorder. Clearance studies, especially if done during furosemide
      and/or hydrochlorothiazide administration, have been helpful in identifying the
      site of tubular involvement. Considering both phenotypic and genotypic data, we
      propose a clinical-pathophysiological and molecular approach to diagnose the
      different tubulopathies associated with hypokalemic metabolic alkalosis.

PMID- 9589377
TI  - A case of deep vein thrombosis in idiopathic nephrotic syndrome with resistance
      to activated protein C.
AB  - We report a case of deep vein thrombosis in a young man with idiopathic nephrotic
      syndrome and resistance to activated protein C. We postulate that patients with
      concurrent nephrotic syndrome and factor V may have an increased risk of
      thrombosis. Screening for factor V Leiden may be indicated in patients with
      idiopathic nephrotic syndrome.

PMID- 9589378
TI  - Reticulocyte indices in patients with end stage renal disease on hemodialysis.
AB  - The diagnosis of iron deficiency anaemia in haemodialysis patients is difficult.
      Two states of deficiency occur, storage (absolute) and functional iron
      deficiency. Conventional measures, lack precision in assessing both storage and
      functional iron deficiency. This study investigated the accuracy of reticulocyte
      indices in comparison to the conventional haematological measures in the
      identification of haemodialysis patients with iron deficiency. A cross-sectional
      study of 72 haemodialysis patients was performed. Mean haemoglobin was 9.6 +/-
      0.16 g/dl. Mean haemoglobin content of reticulocytes (CHr) was normally
      distributed and correlated with MCV, MCH and red cell ferritin. Mean haemoglobin
      concentration of reticulocytes (CHCMr) correlated with MCH. CHr and CHCMr had
      positive predictive values of 0.61 and 0.54 respectively. A low CHr or CHCMr
      identified 5 and 4 and 17 and 21 further patients with iron deficiency with
      normal serum ferritin or transferrin saturation respectively. Reticulocyte
      measures provide a direct measure of adequacy of haemoglobin synthesis in
      haemodialysis patients. In this study their usefulness was somewhat limited, but
      requires further investigation.

PMID- 9589379
TI  - Diabetes mellitus increases the severity of anemia in non-dialyzed patients with
      renal failure.
AB  - We investigated whether the presence of diabetes mellitus (DM) was related to the
      severity of the anemia observed in patients with renal failure who were not
      receiving dialysis. Forty patients were examined, (19 with long-term type II DM
      (DM-CRF), 21 with renal failure due to other causes (non-DM-CRF)). The two groups
      did not differ significantly as to age, sex, serum creatinine or erythropoietin.
      Hemoglobin was significantly (p < 0.005) lower in the DM-CRF patients (9.5 +/-
      2.1 g/dl) than in the non-DM-CRF patients (11.2 +/- 2.0 g/dl). Multiple
      regression analysis indicated that higher serum creatinine levels and the
      presence of DM were independent risk factors for anemia (R2 = 0.494, p < 0.001).
      DM appeared to be a risk factor for the severity of anemia in patients with renal
      failure who were not receiving dialysis.

PMID- 9589380
TI  - Effect of n-3 polyunsaturated fatty acids on cyclosporine pharmacokinetics in
      kidney graft recipients: a randomized placebo-controlled study.
AB  - Highly concentrated marine polyunsaturated fatty acids (n-3 PUFA), affecting the
      lipids and lipophilic drugs metabolism, can interfere with cyclosporine (CyA)
      pharmacokinetics. This prospective, randomized and placebo-controlled, double
      blind study involved 42 kidney graft recipients. From day +1, 21 pts (E) received
      6 g n-3 PUFA (85% EPA + DHA, Esapent, Pharmacia) and 21 pts (P) received placebo
      (olive oil), both reduced to 3 g from day +30 on. A quadruple immunosuppressive
      regimen was employed. Plasma creatinine, lipids and CyA pharmacokinetics were
      investigated 1, 3, 6, 9 and 12 months after graft. The two groups were comparable
      for age, weight, M/F ratio, hypertension prevalence and baseline lipids. Active
      treatment did not affect total and HDL-cholesterol, but significantly lowered
      triglycerides (E:120 +/- 12 vs P:166 +/- 21 mg/dl, p < 0.0001). At one year, E
      pts had lower creatinine than P (1.26 +/- 0.06 vs. 1.88 +/- 0.2 mg/dl, p < 0.05),
      comparable CyA dosage, and a larger CyA area under the curve (AUC) (n.s.), with a
      higher blood peak level (Cmax) (p < 0.04) and less variance in time to peak
      (n.s.). The larger AUC in the E group at all intervals and the better pattern of
      plasma creatinine, with no rise in blood pressure, provided evidence of better
      CyA absorption and metabolism in n-3 PUFA supplemented kidney graft recipients.

PMID- 9589381
TI  - Acute effect of trandolapril on serum erythropoietin in uremic and hypertensive
      patients.
AB  - Anemia associated with ACE inhibitors is rare but it may cause problems
      especially in patients with renal disease. This study assessed the acute effect
      of trandolapril, an ACE inhibitor, on serum erythropoietin (EPO) levels in uremic
      and hypertensive patients. Trandolapril 2 mg/day was given orally for three days
      and blood samples were collected on the first and third day. Trandolapril led to
      a significant decrease in serum EPO in patients with chronic renal failure.
      Although the drug lowered serum EPO in hypertensive patients, this effect was not
      statistically significant. This drop in serum EPO levels may be one of the
      mechanisms by which ACE inhibitors cause anemia, or worsen anemia, in uremic
      patients and further studies are needed to clarify this point.

PMID- 9589382
TI  - Noncompetitive inhibition of nicotinic acetylcholine receptors by endogenous
      molecules.
AB  - Over the past few decades much effort has been expended elucidating the key
      domains of the nicotinic acetylcholine receptor (AChR) responsible for agonist
      binding, ion conduction, and gating. An emerging concept in the receptor field
      has been to consider the receptor entity as a signal transducer that suffers
      modulatory control by allosterically acting ligands. Of particular interest are
      the molecules that inhibit the agonist-evoked ion flux activity in a
      noncompetitive manner: the so-called noncompetitive inhibitors (NCIs). The actual
      knowledge on the action of NCIs was obtained by using several drugs from
      exogenous origin. However, several lines of investigation indicate that the
      receptor protein can be modulated by endogenous substances other than
      acetylcholine. In this regard, we outline the progress evidenced on the
      localization of binding sites for drugs of endogenous origin that have been found
      to directly interact with the AChR in a noncompetitive fashion. Among them we can
      quote lipids such as steroids and fatty acids, the neurotransmitter 5
      hydroxytryptamine (5-HT) and related compounds, as well as the neuropeptide
      substance P. We present the available experimental evidence indicating the
      existence of both luminal (located into the ion channel) and nonluminal (located
      out of the ion channel) binding sites for endogenous NCIs. Particularly, the
      binding site for substance P is found in the delta M2 domain. In addition, the
      locus for 5-HT is putatively located in the ion channel close to the serine ring,
      whereas the binding site for two competitive antagonists of 5-HT receptors (e.g.,
      methysergide and spiperone) is located closer to the external end of the ion
      channel. Instead, fatty acid and steroid molecules bind to nonluminal sites. More
      specifically, fatty acids may bind to the annular lipid domain of the AChR or/and
      to the high-affinity quinacrine site (a NCI from exogenous origin) which is
      located at a nonannular lipid domain. Additionally, steroids may bind to a site
      located on the extracellular hydrophilic domain of the AChR or/and at the lipid
      protein interface, specifically, at the annular lipid domain and/or close to the
      nonannular quinacrine binding site.

PMID- 9589383
TI  - The intracellular domain of p55 tumor necrosis factor receptor induces apoptosis
      which requires different caspases in naive and neuronal PC12 cells.
AB  - Apoptosis is induced in cells via distinct pathways, which may differ according
      to various stimuli and different cell types. One apoptotic stimulus is the
      activation of receptors such as the p55 tumor necrosis factor (TNF) receptor.
      These receptors transduce their apoptotic signals via a cytoplasmic region termed
      the death domain. Here we investigated the apoptotic pathway induced by
      overexpression of the intracellular domain of p55 TNF receptor (p55-IC) in a
      neuronal model system consisting of PC12 cells. Using the tetracycline-regulated
      transactivator system, which allows controlled gene expression, we show that
      overexpression of p55-IC induces apoptosis in both naive and neuronal PC12 cells.
      The apoptosis-inducing effect of p55-IC is blocked by the expression of bcl-2,
      suggesting that p55-IC induces apoptosis in PC12 cells via a pathway controlled
      by bcl-2. The need for caspases in the p55-IC-induced cell death effect in naive
      and neuronal PC12 cells was studied by examining the effects of broad-spectrum
      and specific inhibitors of caspases as well as expression of antisense caspase-2
      RNA. The broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
      fluoromethyl-ketone blocked p55-IC-induced cell death in both naive and neuronal
      cells, suggesting that caspases are needed for this process in both cell types.
      Caspase-1-like proteases are most probably not involved in the process since
      neither expression of crmA nor treatment with the caspase-1-specific peptide
      inhibitor Ac-Try-Val-Ala-Asp-aldehyde had any protective effect. Interestingly,
      expression of antisense caspase-2 RNA blocked the p55-IC-induced cell death in
      naive but not in neuronal PC12 cells, whereas the caspase-3-like specific
      inhibitor Ac-Asp-Glu-Val-Asp-aldehyde partially inhibited this death in neuronal
      but not in naive cells. These results suggest that the apoptosis-inducing effect
      of p55-IC requires different caspases in naive and neuronal PC12 cells.

PMID- 9589384
TI  - Defasciculation of neurites is mediated by tenascin-R and its neuronal receptor
      F3/11.
AB  - Fasciculation and defasciculation of axons are major morphogenetic events in the
      formation of neuronal pathways during development. We have identified the
      extracellular matrix glycoprotein tenascin-R (TN-R) and its neuronal receptor,
      the immunoglobulin superfamily recognition molecule F3, as promoters of neurite
      defasciculation in cerebellar explant cultures. Perturbation of the interaction
      between these two molecules using both antibodies and an antisense
      oligonucleotide resulted in increased neurite fasciculation. The domains involved
      in defasciculation were identified as the N-terminal region of TN-R containing
      the cysteine-rich stretch and the 4.5 epidermal growth factor-like repeats and
      the immunoglobulin-like domains of F3. Fasciculation induced by antibodies and
      the antisense oligonucleotide could be reverted by a phorbol ester activator of
      protein kinase C, whereas the protein kinase inhibitor staurosporine increased
      fasciculation. Our observations indicate that defasciculated neurite outgrowth
      does not only depend on the reduction of the expression of fasciculation
      enhancing adhesion molecules, such as L1 and the neural cell adhesion molecule
      (NCAM), but also on recognition molecules that actively induce defasciculation by
      triggering second messenger systems.

PMID- 9589385
TI  - Target contact regulates GAP-43 and alpha-tubulin mRNA levels in regenerating
      retinal ganglion cells.
AB  - Axotomy of vertebrate neurons leads to the transient upregulation of GAP-43 and
      alpha-tubulin. In adult zebrafish retina, mRNA levels of both genes were
      increased in retinal ganglion cells after optic nerve lesion following a similar
      time course. At 5 days after crush, the mRNA level of GAP-43 was increased nearly
      20 times, whereas a 6-fold increase was observed for alpha-tubulin. Subsequently,
      upon target reinnervation, mRNA levels of both genes were downregulated and were
      2-fold higher than normal at 25 days after crush. Stretching the optic nerve that
      results in diffuse axonal lesions led to the expression of both genes in
      identical subsets of retinal ganglion cells. When regeneration was prevented by
      removing a piece of the optic nerve, mRNA levels remained elevated. Disruption of
      axonal transport by colchicine and vinblastine led to the induction of both genes
      in normal retina. Blocking electrical activity with tetrodotoxin had no effect.
      This indicates that retrogradely transported signals induced by target contact
      regulate GAP-43 and alpha-tubulin transcription. Furthermore, the joint
      regulation of GAP-43 and alpha-tubulin mRNA levels after different kinds of
      lesion suggests that a common pathway underlies the regulation of neuronal GAP-43
      and alpha-tubulin gene expression. In contrast, distinct mechanisms may control
      the extent and maintenance of increased mRNA levels of these genes.

PMID- 9589387
TI  - Sphingosine-1-phosphate induces a Ca2+ signal in primary rat astrocytes and a
      Ca2+ signal and shape changes in C6 rat glioma cells.
AB  - Treatment of rat glioma C6 cells with the beta-adrenergic agonist L-isoproterenol
      leads to a rise in cAMP level and a subsequent change in cell morphology from an
      epithelial to an astrocytic type of appearance. This morphological response is
      reverted by the addition of sphingosine-1-phosphate (S1P) with an EC50 of 10 nM.
      In rat glioma C6 cells loaded with the Ca2+ indicator Fura-2, S1P evoked Ca2+
      release from internal stores and Ca2+ influx from the external medium. Half
      maximal stimulation of the Ca2+ increase was 10-20 nM. A similar Ca2+ signal was
      observed in primary rat astrocytes loaded with the Ca2+ indicator fluo-3.
      Pretreatment of the C6 cells with PMA (162 nM) prevented both the S1P-induced
      Ca2+ increase and the morphological reversion. Ca2+ ions therefore seem essential
      for the morphological reversion by S1P. Pretreatment of the cells with the
      Clostridium botulinum C3 exoenzyme did not affect the reversion of the
      morphological response by S1P, indicating that the small GTP-binding protein Rho
      is not involved in the S1P-induced reversion.

PMID- 9589386
TI  - Gender differences in experimental autoimmune encephalomyelitis develop during
      the induction of the immune response to encephalitogenic peptides.
AB  - Multiple sclerosis (MS) strikes women more often than men. Gender differences in
      experimental autoimmune encephalomyelitis (EAE) parallel those seen in MS. We
      utilized the adoptive transfer model of EAE to determine the role of gender on
      the induction and effector phases of disease. PLP 139-151-sensitized spleen cells
      from female SJL mice were more effective at transferring disease than male cells.
      However, there were no gender differences in the frequency of PLP 139-151
      specific T cells. PLP 139-151-specific female T cell lines induced more severe
      disease than male T cell lines. Disease severity was more strongly linked to the
      sex of the donor T cells, indicating that gender influences the immune response
      primarily during the induction phase.

PMID- 9589388
TI  - Responses induced by tacrine in neuronal and non-neuronal cell lines.
AB  - Alzheimer's disease (AD) is associated with a reduction in cholinergic activity
      as a result of specific neuronal loss. Current potential treatments for the
      disease include both cholinomimetic drugs and anticholinesterase inhibitors. One
      of the drugs approved by the FDA is tacrine (9-amine-1,2,3,4 tetrahydroacridine;
      THA), a strong acetylcholinesterase (AChE) inhibitor. We have studied the effects
      of tacrine on glial and neuronal cells in culture assessing cell survival and
      viability and morphology. Lactate dehydrogenase (LDH) activity and methylthiazol
      diphenyl-tetrazolium (MTT) reduction were used as toxicity indicators. We found
      that tacrine toxicity on rat B12 glial cells and mouse Neuro 2A cells was
      strongly dependent on its concentration (up to 500 microM) and time of exposure.
      The toxic effect was not prevented by serum factors nor by bovine serum albumin.
      Fluorescein-conjugated phalloidin was used to examine the arrangement of actin
      filaments at substrate adhesion regions and cell-cell contacts. Primary events
      following exposure to tacrine included changes in cell morphology, disappearance
      of actin filament bundles, and disruption of focal adhesion contacts. At
      concentrations between 10 and 50 microM, tacrine induced neurite outgrowth in
      Neuro 2A cells, an effect that was not observed in B12 cells, suggesting that
      certain tacrine effects could be specific for neuronal cells. Although similar
      trends of response were observed for both cell types, some differences between
      undifferentiated and differentiated cells were apparent.

PMID- 9589389
TI  - Implication of cyclin-dependent kinases and glycogen synthase kinase 3 in the
      phosphorylation of microtubule-associated protein 1B in developing neuronal
      cells.
AB  - Phosphorylation at certain proline-directed sites on the microtubule-associated
      protein 1B (MAP1B) is a characteristic feature of mitotic neuronal precursor
      cells and developing neurons and is particularly abundant within growing axons.
      This mode of MAP1B phosphorylation disappears from mature neurons, except in
      those neurons that have a high regenerative potential, and is aberrantly up
      regulated in degenerating neurons within the brains of Alzheimer's disease
      patients. Here, we report that this type of MAP1B phosphorylation is practically
      abolished in proliferating neuroblastoma cells that are treated with chemical
      inhibitors of cyclin-dependent kinases. In contrast, these drugs have no
      significant effect on MAP1B phosphorylation in either differentiated
      neuroblastoma cells or cerebellar granule neurons. Interestingly, lithium, which
      is a potent inhibitor of glycogen synthase kinase 3, suppresses this mode of
      MAP1B phosphorylation in differentiated neuroblastoma cells and cerebellar
      granule neurons. This is consistent with a major role of cyclin-dependent kinases
      in catalyzing this type of MAP1B phosphorylation in proliferating neural cells,
      whereas glycogen synthase kinase 3 would be largely responsible for this mode of
      MAP1B phosphorylation in postmitotic neurons that are extending axons. Both
      cyclin-dependent kinases and glycogen synthase kinase 3 might contribute to the
      aberrant MAP1B phosphorylation observed in Alzheimer's disease.

PMID- 9589390
TI  - Mitogen activated protein (MAP) kinase activity is increased in adult mouse
      superior cervical ganglia during culturing.
AB  - We have used adult mouse superior cervical ganglia (SCG) to study the role of
      mitogen activated protein (MAP) kinase activity during axonal outgrowth in vitro.
      An initial peak in activity within the first hours of culture was followed by a
      substantially higher activity after 1 to 2 days, a time when axons were actively
      growing. The latter peak is probably a result of both higher levels of protein
      and increased activity. The addition of nerve growth factor stimulated both
      outgrowth and kinase activity, whereas treating the cultures with the kinase
      inhibitor PD98059 had an opposite effect. Taken together, the results suggest
      that activation of the MAP kinase pathway could be involved in the initiation as
      well as regulation of axonal outgrowth from adult SCG.

PMID- 9589391
TI  - Cell death mediated by Fas-FasL interaction between glial cells and MBP-reactive
      T cells.
AB  - Apoptosis in T cells that have penetrated into the central nervous system (CNS)
      may be important for the physiological control of T cells with potentially
      dangerous reactivities to CNS antigens; such control may be dysfunctional in
      animals suffering from experimental autoimmune encephalomyelitis (EAE). In this
      study we examined the expression of Fas and FasL genes both in myelin basic
      protein (MBP)-reactive T cells and in glial cells and the susceptibility of these
      cells to death induced by Fas/FasL interaction. Both Fas and FasL gene expression
      is detectable in glial cells and MBP-reactive T cells. Cell death is not
      unidirectional: when T cells interact with glial cells death can be induced in
      the former or in the latter population. The ability to induce death of Fas
      expressing cells varies greatly among different lines of MBP-reactive T cells, as
      does resistance to death induction by cells expressing FasL. Moreover, the
      ability of T cells both to deliver and to resist death signals is a function of
      their activation status: T cells freshly activated transmit a stronger apoptotic
      signal to Fas-positive target cells and are also more resistant to FasL-induced
      suicide. Soluble form of FasL provides a convenient titratable means of
      delivering death signals via Fas. However, comparison of the susceptibility of
      different targets to soluble FasL and to FasL expressed on the surface of a
      transfected glial line revealed differences, suggesting that signals arising from
      Fas/FasL interaction may be modulated by additional cell-surface molecules.

PMID- 9589392
TI  - Characterization of ryanodine receptors in oligodendrocytes, type 2 astrocytes,
      and O-2A progenitors.
AB  - In this study we have investigated the expression of ryanodine receptors (RyRs),
      and the ability of caffeine to evoke RyR-mediated elevation of intracellular Ca2+
      levels ([Ca2+]i) in glial cells of the oligodendrocyte/type 2 astrocyte lineage.
      Immunocytochemistry with specific antibodies identified ryanodine receptors in
      cultured oligodendrocytes, type 2 astrocytes, and O-2A progenitor cells, at high
      levels in the perinuclear region and in a variegated pattern along processes.
      Glia acutely isolated from rat brain and in aldehydefixed sections of cortex were
      similarly found to express RyRs. Caffeine (5-50 mM) caused an increase in [Ca2+]i
      in most cultured type 2 astrocytes and in 50% of oligodendrocytes. Responses
      elicited by caffeine were inhibited by pretreatment with ryanodine (10 microM) or
      thapsigargin (1 microM), and the peak response was unaffected by removal of
      [Ca2+]o. O-2A progenitor cells, in contrast, were largely unresponsive to
      caffeine treatment. Pretreatment with kainate (200 microM) to activate Ca2+ entry
      increased the magnitude of caffeine-evoked [Ca2+]i elevations in type 2
      astrocytes and oligodendrocytes, and caused caffeine to activate responses in a
      significant proportion of previously non-responding O-2A progenitors. In both
      type 2 astrocytes and oligodendrocytes, caffeine evoked Ca2+ changes which
      propagated as wavefronts from several initiation sites. These wave amplification
      sites were characterized by significantly higher local Ca2+ release kinetics. Our
      results indicate that several glial cell types express RyRs, and that their
      functionality differs within different cell types of the oligodendrocyte lineage.
      In addition, ionotropic glutamate receptor activation fills the caffeine
      sensitive Ca2+ stores in these cells.

PMID- 9589394
TI  - Analysis of pharmaceutically-important thioxanthene derivatives.
AB  - A review with 92 references is presented that deals with the reported methods of
      analysis of the thioxanthene derivatives of pharmaceutical interest. The review
      includes the methods adopted in dosage forms and biological fluids. A brief
      discussion of the metabolism and pharmacokinetics of this class of compounds is
      also reported.

PMID- 9589393
TI  - Inhibitors of p38 mitogen-activated protein kinase promote neuronal survival in
      vitro.
AB  - Mammalian mitogen-activated protein kinases include the extracellular signal
      regulated protein kinase, the c-Jun amino-terminal kinase, and the p38 subgroups.
      Sustained activation of Jun kinase and p38 have been shown to precede apoptosis
      of PC12 pheochromocytoma cells induced by withdrawal of trophic factors. To
      investigate the possible role of p38 in neuronal apoptosis, we tested the effect
      of two selective p38 inhibitors, the pyridinyl imidazole compounds SB203580 and
      SB202190, on different populations of chick embryonic neurons in vitro. Both
      substances promoted the in vitro survival of sensory, sympathetic, ciliary and
      motor neurons in a dose-dependent fashion. When assayed in nerve growth factor
      stimulated PC12 cells, SB203580 pretreatment inhibited the activation of both
      ribosomal S6 kinases-1 and -2 with the same IC50 (approximately 30 microM) that
      inhibited apoptosis in primary neurons. Thus, p38 inhibitor-sensitive pathways
      may be involved in apoptosis of neurotrophic factor-deprived primary neurons, and
      in activation of ribosomal S6 kinases.

PMID- 9589395
TI  - HPCE methods for the identification and quantitation of antibodies, their
      conjugates and complexes.
AB  - We review here much of the existing literature that deals with analysis,
      resolution, characterization, and (at times) quantitation of antibodies in
      capillary electrophoresis modes. Each major mode of CE shown applicable to
      antibody analysis is described, along with the major applications of that mode
      for antibodies. Discussions are presented as to the mechanisms of antibody
      resolution in CE, interactions of various buffer components with the proteins
      leading to resolution, and methods of quantitation for antibodies. The literature
      is critically reviewed with regard to true application of CE for antibody
      analysis, limitations, information possible, information implied, and which
      samples have actually been assayed by CE modes. The literature is critically
      reviewed up to and including 1996, both for the scientific and commercial
      literature, especially vendor applications and real world applications possible.

PMID- 9589396
TI  - Supercritical fluid extraction of 13-cis retinoic acid and its photoisomers from
      selected pharmaceutical dosage forms.
AB  - 13-Cis retinoic acid (Accutane) was extracted from a cream, gel, capsule and
      beadlet dosage from using supercritical carbon dioxide modified with 5% methanol
      as the mobile phase. The pump pressure and the extraction chamber and restrictor
      temperature were experimentally optimized at 325 atm and 45 degrees C,
      respectively. A 2.5-min static and 5-min dynamic extraction time were used. The
      supercritical fluid extraction (SFE) eluent was trapped in methanol, injected
      into the high-performance liquid chromatographic (HPLC) system, and quantitated
      by ultraviolet detection at 360 nm. Application of the SFE method to spiked
      placebo dosage forms gave 13-cis retinoic acid recoveries of 98.8, 98.9, 98.8 and
      100% for the cream, gel, capsule and beadlet, respectively, with R.S.D.s in the
      range 0.6-0.9% (n = 4). Inter-day percent error and precision of the extraction
      were 1.1-2.0 and 0.2-2.4% (n = 3), respectively, and intra-day percent error and
      precision were 1.0-3.0 and 0.3-2.1% (n = 8), respectively. Percent error and
      precision data for spiked celite samples in the 0.05-1.0 microgram ml-1 range
      were 0.59-4.75 and 1.8-2.1% (n = 3), respectively. The extraction method was
      applied to commercial 13-cis retinoic acid dosage forms and the results compared
      to unextracted samples. Linear regression analysis of concentration versus peak
      height gave a correlation coefficient of 0.9991 with a slope of 7.468 and a y
      intercept of 0.1923. The percent error and precision data were 1.3-5.3 and 0.2
      1.5% (n = 4), respectively. The photoisomers of 13-cis retinoic acid were also
      extracted with the method and recoveries of 90.4-92.4% with R.S.D.s of 1.5-3.4%
      were obtained (n = 4).

PMID- 9589397
TI  - HPLC-fluorescence determination of chlorocresol and chloroxylenol in
      pharmaceuticals.
AB  - The use of 2-chloro-6,7-dimethoxy-3-quinolinecarboxaldehyde as a fluorogenic
      labelling reagent in pre-column derivatization for the HPLC separation of
      chlorophenols has been investigated. The compound reacts (50 min at 110 degrees
      C) with 2- and 4-chlorophenols to give fluorescent ethers that can be separated
      by reversed-phase HPLC and detected at lambda exc = 360 nm, lambda em = 500 nm.
      The experimental conditions for derivatization and chromatographic separation are
      discussed. Applications for the determination of chlorocresol (4-chloro-3-cresol)
      and chloroxylenol (4-chloro-3,5-xylenol) in pharmaceutical formulations (creams,
      ointments) are described.

PMID- 9589398
TI  - Effect of water content in perchloric acid on the non-aqueous potentiometric
      titration of nitrogen-containing compounds.
AB  - In the United States Pharmacopeia (USP), 0.1 N perchloric acid in acetic acid
      volumetric solution (hereafter HClO4 VS) used for non-aqueous titration has
      specified a water content between 0.02 and 0.05%. Preparing this titrant with
      such a narrow range of water content is very time consuming, precludes the use of
      commercially available titrants, and, consequently, prompted an investigation to
      try and expand the range up to 0.5%. In this study, the titrimetric results
      obtained using HClO4 VS containing more water were very close to those obtained
      using the USP specified titrants. A maximum assay difference of 0.7% in the
      titrations of three selected nitrogen-containing compounds, clonidine
      hydrochloride, dipyridamole, and adenosine were observed. The titrimetric results
      obtained using these titrants were also precise with RSDs of not more than 0.4%.
      Therefore, a wider range of water content in HClO4 VS between 0.02 and 0.5% is
      suggested for the USP potentiometric titration of nitrogen-containing compounds.

PMID- 9589399
TI  - High-molecular-weight hyaluronan--a valuable tool in testing the antioxidative
      activity of amphiphilic drugs stobadine and vinpocetine.
AB  - The antioxidative activity of stobadine and vinpocetine was studied in vitro by
      measuring their inhibition effect on the depolymerization of the high-molecular
      weight hyaluronan by hydroxyl radicals. The radicals were generated by the Cu(2+)
      H2O2 system. Hyaluronan depolymerization was monitored by means of size exclusion
      chromatography. The antioxidative activity of stobadine and vinpocetine was
      compared to that of D-mannitol. A 50% inhibition of hyaluronan depolymerization
      was reached at stobadine and vinpocetine concentrations of 1.7 x 10(-6) and 3.0 x
      10(-7) mol l-1, respectively, while a D-mannitol level of 2.6 x 10(-3) mol l-1
      was needed to achieve the same inhibitory effect.

PMID- 9589400
TI  - Gas chromatography-mass spectrometry determination of isosorbide 5-mononitrate
      and related impurities in raw materials and dosage formulations.
AB  - A straightforward quantitative method for gas chromatography-mass spectrometry
      determination of isosorbide 5-mononitrate (IS5MN) and its related impurities such
      as isosorbide (IS), isosorbide diacetate (ISDA) and isosorbide 2-acetate-5
      nitrate (IS2A5N) in raw materials as well as in dosage formulations is developed.
      The recovery of these materials was found to be 100.4 +/- 2.4, 99.3 +/- 4.7, 97.8
      +/- 5.2 and 100.1 +/- 3.1%, while the detection limits were 27.2, 1.26, 1.02 and
      0.78 micrograms in dosage formulations for IS5MN, ISDA, IS2A5N, and IS,
      respectively. The applicability of the method was tested by analysing three
      different formulations of IS5MN.

PMID- 9589401
TI  - Analysis of ACE inhibitors in pharmaceutical dosage forms by derivative UV
      spectroscopy and liquid chromatography (HPLC).
AB  - Derivative UV spectroscopy and high performance liquid chromatography (HPLC) were
      applied to the determination of angiotensin-converting enzyme (ACE) inhibitors in
      their pharmaceutical dosage forms. For spectrophotometric determinations, the
      more appropriate derivative order was selected for each drug: ramipril (third
      order), benazepril (second-order), enalapril maleate (second-order), lisinopril
      (first- and second-order) and quinapril (first-order). Reverse phase HPLC
      procedures (ODS column) were developed able to provide a single, symmetric peak
      for each drug; mixtures A-B, where A is 20 mM sodium heptansulphonate (pH 2.5)
      and B is acetonitrile-THF (95:5 v/v), proved to be suitable mobile phases to
      obtain selective separations of the cited ACE inhibitors. At ambient temperature,
      a low pH value (2.5) was found to be critical to avoid peak splitting and band
      broadening.

PMID- 9589402
TI  - Isolation and structure elucidation of an intermediate in the photodegradation of
      ciprofloxacin.
AB  - Ciprofloxacin decomposes photochemically in aqueous solutions at acidic pH
      forming two major degradation products. One of the products, isolated from
      irradiated solutions by flash chromatography, was 7-[(2-aminoethyl)amino]-1
      cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-3-quinoline carboxylic acid. The compound
      was an intermediate in the photochemical process, which degraded after longer
      exposure with a high-pressure mercury lamp to an aromatic amino-compound, 7-amino
      1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-3-quinoline carboxylic acid. The
      structure of the intermediate was elucidated on the basis of information from
      ultraviolet, mass and nuclear magnetic resonance spectra.

PMID- 9589403
TI  - A sensitive method for the quantification of fluticasone propionate in human
      plasma by high-performance liquid chromatography/atmospheric pressure chemical
      ionisation mass spectrometry.
AB  - A highly sensitive and selective method has been developed for the quantification
      of fluticasone propionate (FP) in human plasma. The drug was isolated from human
      plasma using C18 solid-phase extraction cartridges. The analysis was based on
      high-performance liquid chromatography/atmospheric pressure chemical ionisation
      mass spectrometry (HPLC/APCI/MS), using the 22R epimer of budesonide (BUD)
      acetate, synthesised using acetic anhydride, as internal standard. The mass
      spectrometer was operated in APCI mode with selected ions at tune masses of 473.2
      and 501.2 m/z, corresponding to the MH+ of acetylated (22R)BUD and FP,
      respectively. The mobile phase used was a mixture of 50% ethanol in water with a
      flow rate of 0.45 ml min-1. The system was optimised by tuning the capillary and
      tube lens with a concentrated solution of FP. The recovery of FP from human
      plasma was 86.3%. Linearity of response was obtained over the concentration range
      0.2-4.0 ng ml-1. The intra-assay and inter-assay variability were 6.3 and 2.9%,
      respectively. The lower limit of quantification was 0.2 ng ml-1 when a solid
      phase extraction preceded the HPLC/APCI/MS.

PMID- 9589404
TI  - Determination of p-hydroxyphenylglycine by reaction with o-phthalaldehyde using a
      flow-injection fluorimetric procedure.
AB  - In the present study, new flow injection procedures for the determination of p
      hydroxyphenylglycine using either photometric or fluorimetric detection are
      proposed. The methods are based on the reaction of the amino acid with o
      phthalaldehyde and 2-mercaptoethanol. The calibration graphs based on peak area
      were linear in the ranges 20-300 ng ml-1 with fluorimetric detection and 5-60
      micrograms ml-1 using the photometric mode. The detection limit calculated for
      the fluorimetric procedure was 10 ng ml-1. The method was applied to the
      determination of the free p-hydroxyphenylglycine present in industrial
      pharmaceutical samples of a Dane salt.

PMID- 9589405
TI  - Isolation and quantification of fluoroacetate in rat tissues, following dosing of
      Z-Phe-Ala-CH2-F, a peptidyl fluoromethyl ketone protease inhibitor.
AB  - Peptidyl fluoromethyl ketones (PFMK) are irreversible inhibitors of cathepsin B,
      a cysteine proteinase thought to be involved in the degradation of cartilage. It
      has been speculated that PFMK inhibitors may metabolize in rodents to form
      fluoroacetate (FAC), an extremely toxic poison. A highly selective and sensitive
      separation and detection scheme was developed to measure trace levels of FAC in
      rat tissues following PFMK dosing. The procedure consisted of extracting FAC from
      tissue and spiking the extract with [18O]2-fluoroacetate (18O-FAC) as an internal
      standard. FAC and 18O-FAC were further isolated from matrix components using ion
      exchange, solid-phase extraction. The pentafluorobenzyl esters of FAC and 18O-FAC
      were formed to facilitate the chromatographic separation. Two-dimensional gas
      chromatography coupled with selected-ion-monitoring detection provided the final
      measurement. The assay had a limit of detection of 2 ng FAC per g tissue, and was
      capable of accurately quantitating as little as 10 ng FAC per g tissue with a S/N
      ratio of 40:1. Linearity was established over two orders of magnitude, from 2-500
      ng ml-1, with 5 microliters injected on-column. The method was used to
      demonstrate that FAC was formed in rats following dosing with Z-Phe-Ala-CH2-F, a
      PFMK cathepsin enzyme inhibitor.

PMID- 9589406
TI  - Analysis of acetate counter ion and inorganic impurities in pharmaceutical drug
      substances by capillary ion electrophoresis with conductivity detection.
AB  - Capillary electrophoresis with conductivity detection is a versatile new method
      for the analysis of counter ions in pharmaceutical drug substances. It is a
      sensitive and linear technique for determining inorganic ions and short chain
      carboxylic acids such as acetate. Both acetate counter ion and inorganic
      impurities can be separated and determined in the same assay.

PMID- 9589407
TI  - 750 MHz HPLC-NMR spectroscopic identification of rat microsomal metabolites of
      phenoxypyridines.
AB  - Directly coupled 750 MHz HPLC-1H NMR spectroscopy has been applied to the
      characterisation of low level metabolites of 3-amino-2-(2-fluorophenoxy)pyridine
      (AP) and 3-nitro-2-(2-fluorophenoxy)pyridine (NP) in rat microsomes. In stop-flow
      HPLC-NMR mode, the direct injection of microsomal extracts enabled the separation
      and characterisation of minor metabolites. NP is converted into AP to an extent
      of 93.4% and this is further metabolised to 4- and 6-hydroxy-AP (6 and 0.6%
      respectively). Unequivocal identification of these metabolites was achieved
      without the use of a radiolabel or synthetic standards and thus demonstrates the
      applicability of directly coupled HPLC-NMR to metabolite identification in in
      vitro systems. The potential exists for HPLC-NMR and HPLC-NMR-MS to provide rapid
      metabolic information within the timescale of high throughput lead optimisation
      exercises in drug discovery.

PMID- 9589408
TI  - The determination of pamidronate in pharmaceutical preparations by ion-pair
      liquid chromatography after derivatization with phenylisothiocyanate.
AB  - An analytical method was developed for the determination of pamidronate [(3-amino
      1-hydroxypropylidene)bisphosphonate] by ion-pair liquid chromatography. The
      analyte was derivatized with phenylisothiocyanate into an UV-absorbing
      derivative. The reaction product was cleaned-up by a double ion-pair extraction
      and treated with hydrogen peroxide prior to injection. Both, the detection limit
      and the lower limit of quantification of pamidronate in water were 0.1 microgram
      ml-1 disodium pamidronate. The intra-day precision was 3% for a 5-microgram ml-1
      pamidronate standard solution and the inter-day precision 6% for a 3-microgram ml
      1 solution. The method was applied in the quality control of pamidronate
      injection concentrates and tablets.

PMID- 9589409
TI  - Quantitation and determination of molecular weight distribution of residual water
      soluble extractable polyamines in DMP 504, a poly-alkylamine bile acid
      sequestrant, by aqueous high performance size exclusion chromatography.
AB  - A high performance size exclusion chromatography (HPSEC) method with refractive
      index detection for quantitation and molecular weight determination of
      extractable water soluble polyamines (SPA) in a novel proprietary polymeric
      pharmaceutical compound (DMP 504) is described. The extracted polyamines are
      synthetic impurities as well as potential degradation products of the polymer.
      Data for calibration, precision, solution stability, and limits of detection and
      quantitation are presented to validate the suitability of this method for its
      intended purpose. Response linearity for the poly(2-vinylpyridine) standard is
      demonstrated between 10 and 1000 micrograms ml-1, equivalent to 0.005% and 0.5%
      (w/w) in DMP 504. Molecular weight distributions of SPA extracted from DMP 504
      are presented. No increase in SPA is detected in DMP 504 over 6 months storage at
      room temperature.

PMID- 9589411
TI  - Assay of acyclovir in human skin layers by high-performance liquid
      chromatography.
AB  - This paper describes an assay procedure for acyclovir quantification in human
      skin after in vitro transdermal transport experiments. The procedure employs warm
      distilled water for acyclovir (ACV) extraction and high-performance liquid
      chromatography (HPLC) as analytical method. The procedure has good
      reproducibility, sensitivity and specificity, resulting in a reliable method for
      biopharmaceutical studies of ACV distribution in skin tissue. The chromatographic
      conditions set up, using distilled water as mobile phase, makes the analytical
      procedure simple and easy to perform.

PMID- 9589410
TI  - Use of circular dichroism spectroscopy in determining the conformation of a
      monoclonal antibody prior to its incorporation in an immunoliposome.
AB  - Attachment of antibodies to liposomes endows target specificity to liposomes for
      a certain cell or organ that express the targeted antigenic determinant. These so
      called immunoliposomes hold high promise as targeted drug carriers. One approach
      of immunoliposome preparation involves conjugating antibodies to hydrophobic
      anchors (e.g. fatty acids or phospholipid molecules) for incorporation into the
      liposome membrane. Often, these conjugation reactions are harsh and may result in
      undesirable chemical and structural changes in the antibody molecule. This
      necessitates confirmation of the target specificity of the derivatized antibody
      prior to its incorporation into the liposome. Our approach to this problem is to
      utilize circular dichroism spectroscopy, which can detect subtle structural
      differences in proteins with high reproducibility and accuracy in relatively
      short period of time. In addition, circular dichroism is a non-destructive
      technique. In this study, we demonstrate the ability of circular dichroism to
      confirm the conformation of a model antibody, HYB-241, conjugated to N
      glutarylphosphatidylethanolamine, prior to its mixing with
      dioleoylphosphatidylethanolamine/dioleoylphosphatidic acid to form a target
      sensitive immunoliposome.

PMID- 9589413
TI  - Spectrophotometric determination of moclobemide by charge-transfer complexation.
AB  - A simple and sensitive spectrophotometric method is described for the assay for
      the moclobemide. The method is based on the molecular interaction between the
      drug and chloranilic acid, to form a charge-transfer complex in which the drug
      acts as n-donor and chloranilic acid as pi-acceptor. Chloranilic acid was found
      to form a charge-transfer complex in a 1:1 stoichiometry with a maximum
      absorption band at 526 nm. Conformity with Beer's law was evident over the
      concentration range 4-36 mg 100 ml-1. A complete, detailed investigation of the
      complex formed was made with respect to its composition, association constant,
      molar absorptivity and free energy change. The method has been applied
      successfully to the analysis of commercially available moclobemide tablets with
      good recovery and reproducibility.

PMID- 9589412
TI  - Carotenoid composition of Rosa canina fruits determined by thin-layer
      chromatography and high-performance liquid chromatography.
AB  - The carotenoid composition of fruits of Rosa canina (Rosaceae) was determined
      comparatively by thin-layer chromatography (TLC) and high-performance liquid
      chromatography (HPLC) in total extracts and in three different fractions derived
      from previous separation of the total fruit extract on alumina columns. Both
      chromatographic analyses revealed as major carotenoids: beta-carotene, lycopene,
      beta-chryptoxanthin, rubixanthin, zeaxanthin and lutein. The distribution of
      these compounds was reproducible by TLC and by HPLC. The I-III fractions eluted
      successively from alumina columns by increasing the polarity of the solvents were
      analysed also by TLC and HPLC. In all situations, carotenoids were better
      separated and identified by gradient HPLC systems than by isocratic HPLC or TLC.

PMID- 9589414
TI  - Liquid chromatographic separation of hexopyranosylated cytosine nucleosides from
      their degradation products.
AB  - Development of a liquid chromatographic method which can separate each of a
      series of hexopyranosylated cytosine nucleosides from their degradation products
      formed at acid, neutral and basic pH is described. Both silica-based reverse
      phase and polymer columns were examined. Influence of the mobile phase pH, ion
      pairing agent, concentration of the buffer and type and concentration of organic
      modifier were systematically investigated. The concentration of the ion-pairing
      agent and the buffer were found to have a major effect on selectivity. Samples
      were finally analyzed on a poly(styrene-divinylbenzene), PLRP-S 100 A (8 microns)
      250 x 4.6 mm I.D. column at 60 degrees C and with a mobile phase consisting of
      acetonitrile-sodium octanesulphonate (pH 2.5; 0.02 M)-potassium phosphate buffer
      (pH 2.5; 0.2 M)-water (X:25:50:25-X, v/v, where X is variable).

PMID- 9589416
TI  - Potentiometric determination of ascorbic acid in pharmaceutical preparations
      using a copper based mercury film electrode.

PMID- 9589415
TI  - A preliminary evaluation of accelerator mass spectrometry in the biomedical
      field.

PMID- 9589417
TI  - Prevention: the original adherence issue.

PMID- 9589418
TI  - The Association of Nurses in AIDS Care. Position paper on harm reduction and HIV
      care for drug users: integrating harm-reduction methods and HIV care.
AB  - As the epidemic of HIV disease continues to grow among drug users and their
      sexual partners, new ways must be adopted to do prevention work, outreach, and
      service delivery to this population. The Harm Reduction Model offers methods of
      working with drug users, which are in contrast to traditional methods based on
      confrontation and that require abstinence before change can occur. This position
      paper examines the Harm Reduction Model and outlines areas in which the
      Association of Nurses in AIDS Care can play a role in the expansion of harm
      reduction-based intervention and policies.

PMID- 9589419
TI  - Building community partnerships to improve HIV prevention efforts: implications
      for nurses.
AB  - Acquired immune deficiency syndrome (AIDS), caused by the human immunodeficiency
      virus (HIV), is a major and complex public health crisis. The Centers for Disease
      Control and Prevention (CDC) issued effective community-based HIV prevention
      planning in its 1993 "Supplemental Guidance on HIV Prevention Community Planning"
      through the formation of community planning groups (CPGs). These guidelines are
      reviewed along with behavioral and social science theories that are the crux of
      HIV prevention theory-based research and program development. Nurses' roles in
      community-based HIV prevention as community advocates, HIV prevention program
      planners, practitioners, and researchers are discussed. The article concludes
      with nursing implications for HIV prevention.

PMID- 9589420
TI  - Understanding barriers to condom usage among HIV-infected African American women.
AB  - Drawing on focus group discussions with adolescent and adult HIV-infected women
      between the ages of 16 and 45, this study explores the barriers to condom use
      among women infected with HIV. Although most of the participants were comfortable
      discussing condoms and sexuality, there was little, if any, negotiation of condom
      use with their male partners. Most of the participants used condoms
      inconsistently or not at all. Reasons for nonuse included a lack of trust in the
      reliability of condoms to protect them, a lack of desire for pregnancy
      prevention, and the male partner's refusal to use condoms. Women in discordant
      relationships explained their uninfected partner's refusal to use condoms as
      denial of the risk of contracting HIV or as a way of expressing their love for
      the infected partner. Women also had great difficulty in disclosing their HIV
      status to both family and partners. Prevention efforts to increase condom use
      among HIV-infected women should target both men and women and focus on
      negotiation and communication skills.

PMID- 9589421
TI  - Group sex in gay men: its meaning and HIV prevention implications.
AB  - HIV/AIDS continues to pose a serious health hazard for gay men. Large numbers of
      men continue to become HIV infected each year, despite access to knowledge
      concerning how HIV is transmitted. Although gay men changed their sexual
      practices early in the epidemic, there is growing concern that there is a
      resurgence of risky sexual activities occurring in this group. Of particular
      concern is the resurgence of group sex activities. The purpose of this study was
      to explore the experiences of group sex in gay men to gain insight into the
      meaning of group sex to these men, the context in which it occurs, and men's
      views of how group sexual encounters relate to HIV transmission. The study used a
      qualitative approach to data collection. Ten self-identified gay men who reported
      engaging in group sex activities were interviewed concerning their experiences.
      Men reported that the most likely place for them to engage in group sex
      activities was in sex clubs, and a majority of their discussions centered on
      these clubs. Study data were analyzed using content analysis. Two overall
      categories of responses emerged from men's descriptions of their group sex
      experience: sexual desire and HIV/STD risk behaviors. Four themes--access to sex,
      sexual excitement or stimulation, sexual options, and control and sexual freedom-
      comprised the category of Sexual Desire. The themes identified within the
      category of HIV/STD risk behaviors included reframing risk, rejection of safer
      sex, and alcohol and drug use. The findings of the study suggest that sex in
      group settings such as sex clubs is a reality that must be addressed by HIV
      prevention efforts. Additionally, results indicate that current HIV prevention
      messages are being rejected by many gay men and need to be reevaluated for
      relevance two decades into the HIV/AIDS epidemic.

PMID- 9589422
TI  - Recognizing the phenomenon of readiness: concept analysis and case study.
AB  - The concept of a phenomenon known as readiness will be analyzed. Using the
      Wilsonian method, the concept is broken down into a practical definition that
      allows nurses to assess this phenomenon in clinical practice. Nurses in AIDS care
      work with a patient population whose optimal health is often dependent on the
      ability to incorporate major lifestyle changes into their daily lives. Nursing
      interventions that assist patients to incorporate change must be presented to
      patients at a time when the patient's ability to succeed is optimal. The ability
      to recognize readiness in patients is essential for nurses providing AIDS care.
      This article discusses the concept of readiness, which may be necessary before
      behavior modification can occur. The phenomenon of readiness has application for
      various changes in behaviors, including adherence to primary prevention
      strategies.

PMID- 9589423
TI  - Behavioral factors affecting HIV prevention for adolescent and young adult IDUs.
AB  - Epidemiological and sociobehavioral data regarding HIV-related risk and injection
      drug use among adolescents and young adults are examined to provide insight and
      assistance to nurses delivering preventive intervention and community and
      clinical care. The increase in HIV/AIDS cases among injection drug users (IDUs),
      adolescents, and African Americans strongly suggests that clinical care providers
      acquire a better understanding of the sociocultural and behavioral context within
      which health care is provided. Transition into injection drug use, high-risk
      injecting and sexual behaviors, sociodemographic differences, and the importance
      of social networks are discussed. Nurses are encouraged to provide health
      promotion, disease prevention messages, and health care to IDUs in small
      nontraditional clinical settings and to seek out the assistance of the IDUs'
      social network to increase adherence and compliance to complex prevention and
      therapeutic efforts.

PMID- 9589424
TI  - Condom effectiveness.

PMID- 9589425
TI  - Why don't we have an HIV/AIDS vaccine? When will we have one?

PMID- 9589426
TI  - Whole-grain intake and cancer: an expanded review and meta-analysis.
AB  - Whole grains are nutrient rich and may protect against chronic disease. To study
      this, we previously reviewed 14 case-control studies of colorectal, gastric, and
      endometrial cancers and found consistently lower risk in those with high than in
      those with low whole-grain intake. Questions remained concerning other cancers,
      dietary assessment, quantity consumed, confounding, and differential study
      quality. Here we expand the review to 40 case-control studies of 20 cancers and
      colon polyps. Odds ratios are < 1 for 46 of 51 mentions of whole-grain intake and
      for 43 of 45 after exclusion of 6 mentions with design/reporting flaws or low
      intake. The pooled odds ratio for high vs. low whole-grain intake among the 45
      mentions was 0.66 (95% confidence interval = 0.60-0.72); they range from 0.59 to
      0.78 across four types of dietary questionnaires. Odds ratios were < 1 in 9 of 10
      mentions of studies of colorectal cancers and polyps, 7 of 7 mentions of gastric
      and 6 of 6 mentions of other digestive tract cancers, 7 of 7 mentions of hormone
      related cancers, 4 of 4 mentions of pancreatic cancer, and 10 of 11 mentions of 8
      other cancers. Most pooled odds ratios for specific cancers were in the range of
      0.5-0.8, notable exceptions being breast (0.86) and prostate (0.90). The pooled
      odds ratio was similar in studies that adjusted for few and many covariates. Dose
      response associations were stronger in studies using food-frequency
      questionnaires than in more quantitative questionnaires. The case-control
      evidence is supportive of the hypothesis that whole-grain intake protects against
      various cancers.

PMID- 9589427
TI  - Differential regulation of neurofibromin and p120 GTPase-activating protein by
      nutritionally relevant fatty acids.
AB  - Arachidonic acid, phosphatidic acid, and other lipids inhibit the catalytic
      fragment of neurofibromin more potently than that of p120 guanosine
      triphosphatase-activating protein (GAP). The effects of fatty acids other than
      arachidonic acid on full-length neurofibromin and p120 GAP, to our knowledge,
      have not been studied. In this study, we analyzed the effects of eight
      nutritionally relevant fatty acids on guanosine triphosphatase (GTPase)
      stimulatory activity of full-length neurofibromin and p120 GAP. The fatty acids
      tested were saturated stearic acid, monounsaturated oleic acid, and three n-6 and
      three n-3 polyunsaturated fatty acids. Analysis was performed by Ras
      immunoprecipitation GTPase assay. The full-length p120 GAP expressed in insect
      Sf9 cells and immunoaffinity-purified full-length neurofibromin were used. In
      contrast to neurofibromin, which was readily inhibited by stearic and oleic acid,
      p120 GAP was only weakly inhibited even at high concentrations (> 80 microM).
      Neurofibromin was also two- to threefold more sensitive to inhibition by other
      fatty acids tested. A chimeric protein in which the neurofibromin catalytic
      domain was fused to the NH2-terminal sequences of p120 GAP was used to determine
      that differential sensitivity to fatty acid inhibition maps to the catalytic
      domain of the proteins. These results indicate that nutritionally relevant fatty
      acids can modulate the GTPase function of c-Ha-Ras protein by inhibiting GTPase
      stimulatory activity of two Ras regulators, full-length neurofibromin and p120
      GAP, at physiologically relevant concentrations in vitro.

PMID- 9589428
TI  - Dietary lipid varying in corn and coconut oil influences protein kinase C in
      phorbol ester-treated mouse skin.
AB  - An earlier study indicated that increased levels of corn oil in the diet resulted
      in decreased tumor yield after promotion by the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate in Sencar mouse epidermis (J Leyton, ML Lee, M
      Locniskar, MA Belury, TJ Slaga, et al. Cancer Res 51, 907-915, 1991). In the
      present study we investigated whether corn oil diets could alter the subcellular
      distribution and activity of protein kinase C (PKC), which is part of an
      important signaling pathway in carcinogenesis. We used three 15% (wt/wt) fat
      semipurified diets containing three ratios of corn oil to coconut oil: 1.0%:14.0%
      (Diet L), 7.9%:7.1% (Diet M), and 15.0%:0.0% (Diet H). The translocation to the
      membrane fraction of epidermal PKC by 12-O-tetradecanoylphorbol-13-acetate was
      decreased as the corn oil content of the diet was increased, and this correlates
      with the decrease in tumor yield. The translocation to the membrane fraction of
      specific isoforms of PKC was affected by increased dietary corn oil: the largest
      decreases were in cytosolic PKC-alpha and -beta, and the smallest change was in
      PKC-epsilon. The other isoforms, PKC-delta and -zeta, were unaffected. The major
      constituent of corn oil is linoleic acid, which did not affect the binding of
      phorbol ester to PKC, which suggests that inhibition of such binding was not
      responsible for the effects of increased dietary corn oil. Products of linoleic
      acid metabolism, i.e., arachidonic acid and 13-hydroxyoctadecadienoic acid, also
      did not affect the binding of phorbol ester to PKC. Thus the results of these
      studies suggest that the subcellular distributions of PKC and its isoforms can be
      modulated by dietary lipids.

PMID- 9589429
TI  - Stimulatory effects of high-fat diets on colon cell proliferation depend on the
      type of dietary fat and site of the colon.
AB  - To compare the effects of various types of dietary fat on colon cell
      proliferation used as an intermediate biomarker for colon carcinogenesis, groups
      of 10 male Sprague-Dawley rats were fed one of four high-fat diets (45% of total
      calories from corn oil, butter, beef tallow, and fish oil) for three weeks. As a
      control, a low-fat diet (15% of total calories from corn oil) was fed to a
      separate group. Cell proliferation was measured by in vivo incorporation of
      bromodeoxyuridine into DNA in the proximal and distal colon. Total lipids in
      feces were measured by a gravimetric method. There were significant differences
      in colon cell proliferation among the diet groups, where the high corn oil diet
      stimulated cell proliferation in proximal and distal colon compared with the high
      fish oil diet (p < 0.05). The protective effect of the high fish oil diet on cell
      proliferation was similar to that of the low corn oil diet. The effects of high
      beef tallow and butter diets on colon cell proliferation were highly dependent on
      sites of the colon, because the hyperproliferative effects by these diets were
      found only in the distal colon (p < 0.05). Fecal total lipids and fecal lipid
      concentrations were significantly affected by the dietary fat sources, in that
      the groups fed the saturated fats, such as butter and beef tallow, excreted more
      lipids into feces than did the groups fed the unsaturated fats, such as corn oil
      and fish oil. Fecal lipids were significantly correlated to colon cell
      proliferation in the way that distal colon cell proliferation increases as fecal
      lipids increase. Therefore, these data suggest that high levels of dietary fats
      may not always promote colon carcinogenesis, and the effects may be dependent on
      the types of dietary fat and sites of the colon.

PMID- 9589430
TI  - Absence of an inhibitory effect of a vegetables-fruit mixture on the initiation
      and promotion phases of azoxymethane-induced colorectal carcinogenesis in rats
      fed low- or high-fat diets.
AB  - The potential inhibitory effects of a vegetables-fruit mixture on the initiation
      and promotion phases of azoxymethane-induced colorectal carcinogenesis were
      examined in rats fed low- or high-fat diets. Rats were fed low-fat diets (20
      energy percent, Diets A and B) or high-fat diets (40 energy percent, Diets C and
      D), supplemented with a vegetables-fruit mixture (19.5% wt/wt, Diets B and D) or
      unsupplemented (Diets A and C) for 36 weeks. After the animals were maintained on
      the respective diets for four weeks, they were given three weekly injections of
      azoxymethane at 15 mg/kg body wt sc. Eight weeks after the start of the study,
      animals maintained on Diet A were switched to Diet B or C or maintained on the
      same diet. Animals maintained on Diet B or D were switched to Diet A or C,
      respectively. Furthermore, animals maintained on Diet C were switched to Diet A
      or D or maintained on the same diet. Multiplicity of colorectal tumors did not
      differ between groups fed a vegetables-fruit mixture during the initiation or the
      promotion phase (Group B-->A vs. Group A-->B; Group D-->C vs. Group C-->D).
      However, multiplicity was significantly lower in animals fed low-fat diets than
      in animals fed high-fat diets in combination with a vegetables-fruit mixture
      (Group A-->B/B--A vs. Group C-->D/D-->C). Furthermore, multiplicity was
      significantly increased in groups fed a high-fat diet during the promotion phase
      only in comparison with animals fed a low-fat diet during the whole experiment
      (Group A-->C vs. Group A-->A). No other differences in multiplicity or tumor
      incidences were observed among the eight experimental groups.

PMID- 9589431
TI  - A nested case-control study of dietary factors and the risk of incident
      cytological abnormalities of the cervix.
AB  - Several earlier case-control studies reported inverse associations of cervical
      squamous intraepithelial lesions (SIL) with high dietary or biomarker levels of
      carotenoids, folate, and vitamins C and E. However, most studies did not measure
      the primary causal factor, cancer-associated genital human papillomaviruses
      (HPV), now detected by sensitive viral DNA tests. This nested case-control study
      assessed whether high dietary intakes of these nutrients, plus zinc and vitamin
      A, reduced SIL risk in cancer-associated HPV DNA-positive women. Using a 60-item
      food-frequency questionnaire, nutrient estimates were obtained for 33 incident
      cases with high-grade lesions, 121 with low-grade lesions, 97 with equivocal SIL,
      and 806 cytologically normal controls sampled from a large prospective cohort
      study. Baseline cervicovaginal lavages were tested for HPV DNA by the polymerase
      chain reaction. Among DNA-positive cases (n = 68) and controls (n = 69), age
      adjusted odds ratios (ORs) of SIL in the highest vs. the lowest nutrient
      quartiles were 1.4 [95% confidence interval (CI) = 0.5-4.2] for vitamin A, 0.6
      (CI = 0.2-2.0) for beta-carotene, 1.3 (CI = 0.4-3.6) for vitamin C, 1.0 (CI = 0.4
      3.6) for vitamin E, 0.7 (CI = 0.3-2.1) for folate, and 0.8 (CI = 0.3-2.2) for
      zinc. ORs in HPV DNA-negative women approximated 1.0, with the exception of
      vitamin E (OR = 0.5, CI = 0.3-0.9). These results do not support a protective
      role for the above nutrients against low-grade or equivocal SIL, which
      constituted the majority of diagnoses in this study.

PMID- 9589433
TI  - Altered serum amino acid profiles in head and neck cancer.
AB  - Patients who develop squamous cell carcinoma of the head and neck (SCCHN) are
      often malnourished because of poor dietary habits, excessive alcohol consumption,
      local tumor effects, tumor-induced cachexia, and the effects of various
      therapies. The composition of the diet may be a risk factor for the development
      of head and neck cancer as well as tumor progression. This study compares the
      amino acid profiles in the banked serum of patients with and without SCCHN. In
      comparison to the control group, patients with SCCHN had significantly decreased
      preoperative serum levels of alanine (p = 0.006), asparagine (p = 0.002),
      aspartic acid (p = 0.0001), glycine (p = 0.0002), histidine (p = 0.002), 3
      methylhistidine (p = 0.001), ornithine (p = 0.001), phenylalanine (p = 0.002),
      serine (p = 0.002), taurine (p < 0.0001), and threonine (p = 0.001). Levels of
      cystine were significantly elevated in the group of cancer patients (p < 0.0001).
      No significant differences were noted on the basis of T stage, N stage, or
      nutritional status. Serum levels increased postoperatively for the majority of
      the amino acids tested. Postoperative histidine levels were associated with tumor
      recurrence (p = 0.04). Serum amino acid levels may prove to be useful markers of
      disease status and provide prognostic information.

PMID- 9589432
TI  - Effects of dietary n-3-to-n-6 polyunsaturated fatty acid ratio on mammary
      carcinogenesis in rats.
AB  - We investigated the effects of the dietary n-3-to-n-6 polyunsaturated fatty acid
      (PUFA) ratio (n-3/n-6 ratio) on mammary carcinogenesis induced by 7,12
      dimethylbenz[a]anthracene in rats by feeding them several types of dietary fat
      with a fixed PUFA-to-saturated fatty acid ratio. Dietary fat was fed to the rats
      as 10% of the total feed weight, starting two weeks before the initiation. An
      increase in the n-3/n-6 ratio did not suppress the incidence or reduce the
      latency of mammary tumor development. The number and weight of mammary tumors per
      tumor-bearing rat tended to be large in the group with an n-3/n-6 ratio of 7.84
      compared with those in the other groups. As the n-3/n-6 ratios were elevated, the
      total number and weight of tumors increased gradually. The prostaglandin E2
      (PGE2) concentration in mammary tumor tissue was markedly low in the group with
      an n-3/n-6 ratio of 1.03 compared with the group with an n-3/n-6 ratio of 0.01.
      In addition, PGE2 concentrations were almost constant when n-3/n-6 ratios were >
      1.03. These results suggested that the increase in the n-3/n-6 ratio of dietary
      fat with the fixed PUFA-to-saturated fatty acid ratio cannot suppress the mammary
      carcinogenesis but can promote development of tumors, despite reduced PGE2
      concentration in the tumor.

PMID- 9589434
TI  - Fruit and vegetable consumption of rural African Americans: baseline survey
      results of the Black Churches United for Better Health 5 A Day Project.
AB  - The objective of this study was to determine baseline fruit and vegetable
      consumption (total and specific) among rural African Americans participating in a
      5 A Day intervention study and factors associated with this dietary intake. A
      telephone survey was administered to 3,737 adult members of 50 black churches
      from 10 rural counties in North Carolina. The survey measured demographic
      characteristics, knowledge and beliefs regarding cancer and nutrition, and food
      frequency data related specifically to fruit and vegetable consumption.
      Associations between fruit and vegetable consumption and income, education, age,
      gender, marital status, the presence of children within the household, and
      awareness of the 5 A Day program were explored using descriptive and regression
      analyses. Food-frequency data showed a mean intake of 3.7 +/- 2.4 daily servings
      of fruits and vegetables within this population of rural African Americans.
      Twenty-three percent of the participants reported eating five or more daily
      servings of fruits and vegetables. Significant associations were found between
      fruit and vegetable intake and both age and gender (p < 0.001), with older
      females consuming the most and younger males consuming the least fruits and
      vegetables. Findings from this rural African American population parallel
      national studies showing that US intake of fruits and vegetables falls short of
      the 5 A Day guidelines. Female gender and advancing age were positively
      associated with fruit and vegetable intake. Study results reinforce the need to
      promote the 5 A Day message. Such messages may prove most beneficial if targeted
      toward younger adult males, whose fruit and vegetable intakes are especially low.

PMID- 9589435
TI  - Dietary nitrosamines, heterocyclic amines, and risk of gastric cancer: a case
      control study in Uruguay.
AB  - To study the effects of dietary chemicals like nitrosodimethylamine and 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine, resulting from the cooking method of red
      meat, on gastric carcinogenesis, a case-control study was conducted in Uruguay, a
      country with areas of high rates of gastric cancer. The study involved 340 cases
      and 698 controls, who were interviewed between January 1993 and December 1996.
      Dietary nitrosodimethylamine was associated with an increased risk of gastric
      cancer [odds ratio (OR) = 3.6, 95% confidence interval (CI) = 2.4-5.5], whereas
      dietary 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (a potent mutagen derived
      from the frying and broiling of red meat) showed an OR of 3.9 (95% CI = 2.3-6.4).
      Both chemicals displayed independent effects, and its interaction followed a
      multiplicative model with an elevated OR of 12.7 (95% CI = 7.7-21.2). These
      results suggest that salted and barbecued meat, frequent items in the Uruguayan
      diet, and the resulting chemicals from the cooking methods of both types of meat
      are significantly associated with a high risk of stomach cancer.

PMID- 9589436
TI  - Retardation of experimental tumorigenesis and reduction in DNA adducts by
      turmeric and curcumin.
AB  - Turmeric and its active principle curcumin have been extensively investigated for
      their antimutagenic and antioxidant effects in bacterial and animal systems.
      Because oral cancers are common in India, an experimental model of 7,12
      dimethylbenzanthracene-induced buccal pouch tumors in Syrian Golden hamsters was
      used to evaluate the tumor retardation effects of turmeric and curcumin. Turmeric
      and/or curcumin was administered in the diet and/or applied locally for 14 weeks
      along with 7,12-dimethylbenzanthracene. After the experimental period, the
      animals were sacrificed and oral pouches were examined for tumor number and size.
      DNA adducts were estimated by 32P postlabel assay in the cheek pouches.
      Neoplastic changes were graded by histopathology. The results of the study
      suggest that turmeric or curcumin in the diet and/or applied locally
      significantly reduced DNA adducts at the target site. Tumor number and tumor
      burden were significantly lower (p < 0.05) in the animals that received turmeric
      in the diet and applied locally. The histopathological examinations suggested
      that the neoplastic grading was least in the animals fed or painted with curcumin
      (p < 0.05). The current study demonstrates that turmeric or curcumin administered
      in the diet or applied as paint may have a plausible chemopreventive effect on
      oral precancerous lesions.

PMID- 9589437
TI  - In defense of the Pap smear.

PMID- 9589438
TI  - Ovulatory cycles, pregnancy outcome and complications after surgical treatment of
      polycystic ovary syndrome.
AB  - The purpose of this review is to survey the literature on the various
      laparoscopic surgical techniques for ovulation induction in polycystic ovary
      syndrome (PCOS) patients (multiple biopsies, electrocauterization, laser
      vaporization, ovarian resection), compared with traditional ovarian resection by
      laparotomy. Relevant studies were identified through a search of a computerized
      bibliographic database and cross-referencing of relevant medical journals. Data
      regarding 1803 anovulatory PCOS patients have been analyzed, 679 of them treated
      by classical ovarian resection after laparotomy, 720 by laparoscopic
      electrocauterization, 322 by laparoscopic laser vaporization, and 82 by
      laparoscopic multiple biopsies. The percentages of miscarriages, twin
      pregnancies, and ectopic pregnancies have been calculated analyzing 1076
      pregnancies achieved spontaneously or after medical therapy after failure of
      various surgical attempts. The percentage of adhesions has been calculated among
      343 patients submitted to second-look surgery. All of the surgical techniques
      proved equally effective, with an average ovulation rate of 78.8 percent, a
      cumulative pregnancy rate of 58.5 percent, a miscarriage rate of 15.9 percent, a
      twin pregnancy rate of 2.1 percent, and an ectopic pregnancy rate of 1.6 percent.
      Hormone variations after surgery consisted in a remarkable fall in serum androgen
      levels (androstenedione and testosterone), in an FSH increase, reduced biological
      activity and reduced amplitude of LH pulses, and an LH/FSH ratio trending toward
      normal levels. Moreover, after surgery, the ovaries showed higher responsiveness
      to drug-induced ovulation. Adhesions were less frequent after laparoscopic
      multiple biopsies, but they were observed in about 90 percent of patients after
      resection by laparotomy, in 30 percent of patients after laparoscopic
      electrocauterization, and in 50 percent after laparoscopic laser vaporization. In
      conclusion, at present laparoscopic methods for inducing ovulation can be
      performed in PCOS infertile patients if medical treatment fails to give the
      desired results. However, additional controlled trials are required to assess the
      long-term effects of these procedures.

PMID- 9589439
TI  - Interstitial cystitis and the gynecologist.
AB  - Interstitial cystitis (IC) is a predominantly female condition with the
      presenting symptoms of frequency of micturition and pain. The diagnosis is
      confirmed by bladder visualization at cystoscopy during filling, emptying, and
      redistension. The epidemiology, proposed etiologies, and current therapies for
      interstitial cystitis are discussed. The condition of IC is poorly understood and
      has no specific histological characteristics. However, there is much that can be
      offered to the IC sufferer to relieve or cure her symptoms. It is hoped that the
      recent decade of increasing research activity will be fruitful in answering
      questions of etiology and pathogenesis, and offering hope for new therapies and
      ultimately cure.

PMID- 9589440
TI  - Tubal pregnancy: a review of current diagnosis and treatment.
AB  - Ectopic pregnancy accounts for 2 percent of all pregnancies in the United States,
      and contributes substantially to maternal morbidity and mortality. Risk factors
      for the development of ectopic pregnancy are described, but less than 50 percent
      of women with ectopic pregnancy actually give a history of such risk factors. The
      initial history and physical examination of patients who eventually are found to
      have ectopic pregnancy can be misleading, resulting in early misdiagnosis.
      Failure to diagnose ectopic pregnancy before tubal rupture limits treatment
      options. However, with a high index of suspicion, and a combination of
      biochemical and ultrasound parameters, early diagnosis of ectopic pregnancy can
      be achieved, permitting medical or conservative surgical treatment options.
      Future reproductive potential after treatment of ectopic pregnancy is limited,
      with only approximately one third of affected women ever subsequently delivering
      a live-born infant. Future fertility is more dependent on the condition of the
      contralateral fallopian tube than on the specific type of therapy used to treat
      the affected tube. There is no consensus on which treatment is most effective,
      minimizing the risk of persistent ectopic pregnancy, while providing the optimum
      future fertility potential.

PMID- 9589442
TI  - Adjudicating claims.
AB  - This chapter discusses the adjudication and case management processes and
      outlines sources of information and factors leading to denial of claim.

PMID- 9589441
TI  - An overview of workers' compensation.
AB  - The authors compare and contrast the U.S. and Canadian systems; describe the
      roles of government, employers and employees, and insurance providers; examine
      the economics of workplace risk; assess different systems in six states and two
      provinces; and indicate challenges to be met.

PMID- 9589443
TI  - Evaluation of the worker with suspected occupational lung disease.
AB  - A systematic approach to evaluation of suspected occupational lung disorders is
      presented to assist the health care professional with diagnosis, treatment, and
      prognosis, as well as management of the disease in the workplace.

PMID- 9589444
TI  - Evidence-based medical dispute resolution in workers' compensation.
AB  - There is a trend toward insisting on empirical evidence, rather than relying on
      expert judgement, in both health care and law. Medical knowledge is applied in
      law to provide solid logic for the physician's opinion and to place the opinion
      in a context that assists the adjudicator. Dr. Guidotti examines workers'
      compensation disputes in the light of hypothesis development and application of
      scientific theory.

PMID- 9589445
TI  - Applying epidemiology to adjudication.
AB  - Dr. Guidotti describes an epidemiologic study of firefighters, conducted by the
      University of Alberta, to underscore the difficulties of obtaining data and the
      years that can pass before analysis can even begin. He then delineates problems
      encountered when interpreting data in any epidemiologic study.

PMID- 9589446
TI  - Disability evaluation.
AB  - A physician may be called upon to evaluate disability in the roles of impartial
      judge of impairment, expert witness in a legal case, or treating physician.
      Critical to these processes are discernment between disability and impairment, an
      understanding of legal responsibilities, and knowledge of the elements of
      examinations and reports.

PMID- 9589447
TI  - Independent medical evaluations and impairment ratings.
AB  - A significant need exists for quality independent medical evaluations (IMEs). The
      examiner must understand disability issues to specifically answer the questions
      of the client who requested the IME. The authors discuss these issues and outline
      step-by-step the performance of a thorough evaluation and the compilation of a
      complete report.

PMID- 9589448
TI  - Employer services.
AB  - Reduction of workers' compensation costs is a competitive advantage for
      businesses. Insurers offer many services, such as loss prevention programs and
      disability management, to help employers minimize the financial impact of
      workplace injuries and diseases.

PMID- 9589449
TI  - Health care management in workers' compensation.
AB  - A high-performing, effective health care delivery system is critical to the
      recovery of injured workers within a workers' compensation insurance system.
      Timely and effective health care has the potential to minimize indemnity costs
      and therefore contribute to the insurer's financial state. While costs remain a
      concern to insurers, cost-containment initiatives within the health care arena
      have evolved from a strict "deep discount" approach to more sophisticated health
      care strategies that follow managed care-style models. In the future, health care
      strategies are likely to become more integrated within the business operations of
      workers' compensation insurance systems. The next evolution of health care
      strategy within workers' compensation will likely include consensus-based
      contracts with providers that stipulate the role and function of each party while
      reinforcing a continuous improvement mindset. It is probable that a component of
      this evolving system will include shared risk and reimbursement that is based on
      performance. Insurers who begin to evaluate the true impact of a comprehensive
      health care strategy will find it necessary and advantageous to modify their
      business relationship with health care providers. Those who are able to
      articulate a business strategy that capitalizes on the skills of the health care
      community are likely to gain a competitive advantage. Most importantly, this
      bridging of intellectual capacity across the insurance and health care domains
      will result in a delivery system that is valued by, and contributes to, its key
      participants--the employers and the injured workers.

PMID- 9589450
TI  - Workers' compensation reform: 180 days in Massachusetts.
AB  - While not the usual Occupational Medicine review article, this description of the
      1991 workers' compensation reforms in Massachusetts reveals some of the
      difficulties and possibilities inherent in such an undertaking.

PMID- 9589452
TI  - Workers' compensation systems: purpose and mandate.
AB  - This historical overview of workers' compensation reveals the legal, sociologic,
      and economic benefits to both employees and employers.

PMID- 9589451
TI  - Uses of workers' compensation data in epidemiology research.
AB  - Contrary to general opinion, workers' compensation data can be helpful in
      epidemiologic research. Dr. Goldsmith assesses several studies based on data
      culled from workers' compensation or disability programs and explains how
      valuable information was derived.

PMID- 9589453
TI  - Workers' compensation appeals systems in Canada and the United States.

PMID- 9589454
TI  - Reducing workers' compensation fraud: a deterrent approach.
AB  - Popular misconceptions view economic crime against workers' compensation systems
      as victimless and therefore acceptable. This chapter argues that the courts must
      express strong denunciation of this fraud to engender a climate of deterrence.
      The law and order approach developed in Alberta, where Workers' Compensation
      Board investigators are given police powers, is examined.

PMID- 9589455
TI  - Fraud in the workers' compensation system: origin and magnitude.
AB  - Apparently, most investigations of workers' compensation fraud focus on the
      worker and cost more than the amount of money stolen. Although less is known
      about the extent of employer fraud, the dollars involved often are in the
      millions. Therefore, disproportionately policing workers is counterproductive.

PMID- 9589456
TI  - Effective intervention to reduce occupational injuries in Alberta: a case study
      of financial incentives.
AB  - High injury rates in particular industries in Alberta, Canada were the impetus
      for government initiatives to control injury frequency and severity. Safety
      associations, a financial incentives program, research projects, and safety
      demonstrations substantially decreased injury rates within 5 years. Since then,
      companies manage their own performance, but undergo periodic audits.

PMID- 9589457
TI  - Stromal reaction in cancer tissue: pathophysiologic significance of the
      expression of matrix-degrading enzymes in relation to matrix turnover and
      immune/inflammatory reactions.
AB  - Cancers are characterized by invasive growth and distant metastasis. Cancer cells
      not only destroy the pre-existing extracellular matrix, but cancer invasion per
      se usually induces new matrix formation by activation of stromal cells; that is,
      desmoplastic reaction. This process includes both matrix production and
      degradation; that is, the remodeling process. The similarity between desmoplastic
      reactions in cancer stroma and the wound healing process has already been pointed
      out, and it has been well documented that matrix-degrading processes are actively
      involved in the would healing process. A recent study revealed that most matrix
      degrading enzymes, generally considered to be one of the main mechanisms of
      cancer invasion and metastasis, are originated from stromal cells. Based on these
      preconditions, the present review postulates that the abundant expression of
      matrix-degrading enzymes by fibroblasts, coupled with the abundant expression of
      type I procollagen, is involved in the matrix remodeling processes occurring in
      cancer stroma; that is, the mechanism similar to the wound healing process. Next,
      macrophages distributed along the invasive margin are known to express matrix
      degrading enzymes/factors. Data from past studies of colon carcinoma indicate
      that the tissue expression of matrix metalloproteinase-9 and urokinase-type
      plasminogen activator receptor is inversely associated with simultaneous liver
      metastasis and infiltrating growth pattern. Previous clinicopathologic data have
      indicated that immune/inflammatory cells are one of the factors for a favorable
      prognosis. This suggests that the expression of matrix-degrading enzymes/factors
      by these host cells may be involved in host immune/inflammatory reactions, and
      that the net function of these cells can be defensive towards the host. Data from
      past studies of colon carcinoma on the expression of the intercellular adhesion
      molecule-1 suggest that the interaction between macrophages, lymphocytes, and the
      phenotypes of venules distributed along the invasive margin, further support the
      pro-inflammatory milleu there. Therefore, the matrix degradation process in
      cancer tissue is multifunctional: besides the involvement in cancer invasion and
      metastasis, the matrix degradation process is also involved in the tissue
      remodeling process and in the immune/inflammatory reaction occurring in the
      stroma.

PMID- 9589458
TI  - Costimulatory molecules (CD80 and CD86) on Reed-Sternberg cells are associated
      with the proliferation of background T cells in Hodgkin's disease.
AB  - To elucidate the relationship between Reed-Sternberg (R-S) cells and background T
      cells, the expression of CD80 and CD86 of R-S cells in Hodgkin's disease (HD),
      and the ligand CD28 expression and the MIB-1 index of background T cells were
      immunohistochemically investigated. CD80 and CD86 were found to be expressed on R
      S cells in almost all cases of HD. CD28 was expressed with strong intensity on
      many background T cells around R-S cells. The MIB-1 index of background T cells
      was 30.3% (range, 15.5-38.9%) and was much higher than 10.9% (range, 9.8-11.7%)
      in B cell lymphomas. These results suggest that the interaction between CD80 and
      CD86 on R-S cells, and CD28 on background T cells may induce T cell proliferation
      and be associated with tumor mass of HD.

PMID- 9589459
TI  - p53 protein expression in non-Hodgkin's lymphomas is infrequently related to p53
      gene mutations.
AB  - Accumulation of the p53 protein has been found in several types of lymphomas.
      However, p53 gene mutations have been infrequently demonstrated in some specific
      types of lymphomas. In the present study, a correlation between p53
      immunoreactivity and p53 gene mutations in a large panel of non-Hodgkin's
      lymphoma (NHL) cases is attempted. A panel of 202 cases of NHL was evaluated by
      immunohistochemical staining for p53 protein. All cases that were
      immunohistochemically positive for p53 protein were analyzed by the polymerase
      chain reaction (PCR) single strand conformation polymorphism (SSCP) method to
      identify mutations within the p53 gene. In order to confirm the mutation,
      sequencing of PCR-amplified p53 gene segments was performed. Overexpression of
      p53 protein was found in 59 of the 202 cases of NHL, but only four of these 59
      cases showed a shift on SSCP analysis, and point mutations were detected in three
      of them by the subsequent sequencing. p53 immunoreactivity was generally greater
      in high-grade lymphoma. The results of this study suggest that
      immunohistochemical reactivity for p53 protein is not a reliable indicator of the
      presence of their structural alterations of p53 gene exons 4-9 in NHL.

PMID- 9589460
TI  - Upregulation of nucleobindin expression in human-activated lymphocytes and non
      Hodgkin's lymphoma.
AB  - Nucleobindin (Nuc) was originally found to be an enhancement factor of anti-DNA
      antibody production secreted by a lymphoid cell line derived from a
      lymphoproliferative MRL/lpr mouse. It has been shown that Nuc has a unique
      structure containing a DNA- and two calcium-binding domains, and a leucine zipper
      motif, but its biological roles have not yet been fully elucidated. Expression of
      Nuc was first studied in human lymphocytes. Expression of Nuc mRNA in normal
      peripheral blood mononuclear cells was significantly increased upon mitogen
      stimulation. Anti-human Nuc monoclonal antibody H-1D8 immunoprecipitated Nuc
      protein in the nuclear extract of Molt-4 cells. Furthermore, in the
      immunohistochemical staining of tumor specimens from 108 patients with non
      Hodgkin's lymphoma (NHL) with H-1D8, H-1D8-positive cells were observed in nearly
      all cases in varying frequency. According to the Working Formulation, the
      percentage of cases in which more than 90% of the tumor cells were stained with H
      1D8 was 65% in the high grade of the histological malignancy, 54% in the
      intermediate grade, and 22% in the low grade; however, normal cells surrounding
      the tumor cells were virtually negative for H-1D8. These results showed that the
      level of Nuc expression in human lymphocytes reflects the status of activation or
      proliferation of the cells, thus providing a clue for the further investigation
      into biological roles of Nuc. In addition, it might be applicable to the
      clinicopathological estimation of NHL as a novel indicator.

PMID- 9589461
TI  - Hyperplastic foci in chronic liver disease: their proliferative activity assessed
      by nucleolar organizing region.
AB  - In the cirrhotic and precirrhotic liver, there may be small foci with increased
      cellularity and amphophilic cytoplasm. These are microscopic lesions that do not
      form macroscopically detectable nodules, which differ from the macroscopically
      apparent nodules of dysplastic nodules. In the present study, we assessed the
      proliferating activity of 12 hyperplastic foci in 11 patients with cirrhosis or
      chronic hepatitis, by staining for agyrophilic nucleolar organizing regions
      (AgNOR). The mean AgNOR count per nucleus in the hyperplastic foci ranged from
      0.96 to 1.36 (mean, 1.13; SD 0.12), and from 0.81 to 1.06 (mean, 0.94; SD 0.08)
      in the controls. The AgNOR count in the hyperplastic foci was significantly
      higher than that in the controls (P < 0.01). Small hyperplastic foci show
      increased proliferative activity. Further study on these foci is required to
      clarify their relation to hepatocarcinogenesis.

PMID- 9589462
TI  - Analysis of K-ras oncogene mutation directly applied to atypical cell clusters on
      cytologic smear slides of bile and pancreatic juice.
AB  - To develop an objective reference for the cytological evaluation of atypical
      cells in bile and pancreatic juice, we analyzed K-ras oncogene mutation in
      atypical cell clusters, which were collected directly from cytological smear
      slides; 50 samples (cell clusters) from 31 smear slides of 21 patients with
      carcinomas of the pancreatic head region, and nine samples from eight cases of
      benign disease. These cell clusters (5-1000 cells/cluster) were selectively
      suspended in buffer containing proteinase K, and subjected to DNA extraction. K
      ras codon 12 mutation was determined by polymerase chain reaction amplification,
      followed by digestion with BstNI. The K-ras gene was amplified in 20 of 21 cases
      with carcinoma (34/50 samples), and in seven of eight cases with non-neoplastic
      disease (8/9 samples). Among the cases of which primary tumors showed K-ras
      mutation, amplification was successful in 10 of 11 cases; mutation was
      demonstrated in three of seven cases with cytologically atypical cells (4/11
      samples), and in three of three cases with cytologically malignant cells (5/7
      samples). No mutation was identified in the 10 cases of carcinoma without K-ras
      mutation (0/15 samples), or in eight cases of non-neoplastic disease (0/8
      samples). Cytological details could be comparatively evaluated between atypical
      cell clusters with or without mutation on the same smear slides in two cases.
      This type of direct analysis of atypical cell clusters may be useful in the self
      assessment of cytological diagnosis of bile and pancreatic juice.

PMID- 9589463
TI  - Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer
      patients with lymph node metastases: a retrospective immunohistochemical
      analysis.
AB  - The prognostic significance of Ki-67, p53, and Bcl-2 expression was evaluated in
      prostate cancer patients with lymph node metastases. Immunohistochemical staining
      of archived material obtained from 56 patients was performed by the streptavidin
      biotin method. Univariate survival analysis showed that a Ki-67 labeling index
      (Ki-67 LI) of > or = 8.4 in the primary tumor identified a group of patients with
      a significantly poorer prognosis (P < 0.001). furthermore, a Ki-67 LI of > or =
      8.7 in the nodal metastatic tumor was also associated with a poorer prognosis (P
      < 0.01). Multivariate analysis showed that the Ki-67 LI of primary tumors (P <
      0.01) and lymph node metastases (P < 0.01) had independent prognostic value. p53
      and Bcl-2 expression had no prognostic value in patients with prostate cancer and
      lymph node involvement. The Ki-67 LI has more prognostic value than p53 and Bcl-2
      expression for patients with prostate cancer that has spread to the lymph nodes.

PMID- 9589464
TI  - Solitary fibrous tumor of the pleura causing recurrent hypoglycemia by secretion
      of insulin-like growth factor II.
AB  - A case of malignant solitary fibrous tumor (SFT) is reported, occurring in a 61
      year-old man with frequent hypoglycemia. Endocrinological analyses showed high
      serum levels of insulin-like growth factor II (IGF-II) and suppressed secretion
      of insulin. After the removal of a pleural tumor, which weighed 3150 g, serum IGF
      II levels returned to normal and hypoglycemic attacks ceased. The tumor was
      composed of uniform spindle cells arranged in bundles, and fascicles with varying
      amounts of collagen and reticulin fibers. Mitotic figures at the rate of 6/10
      high-power fields, and frequent foci of necrosis and hemorrhage were seen. Almost
      all of the tumor cells were immunohistochemically positive for vimentin and CD34.
      Electron microscopy revealed the immature mesenchymal or myofibroblastic nature
      of the tumor cells. These findings are consistent with malignant SFT of the
      pleura. Moreover, the tumor produced IGF-II mRNA as demonstrated by northern blot
      analysis. Thus, hypoglycemia of this patient was induced by SFT through the
      production and secretion of IGF-II.

PMID- 9589465
TI  - Pericellular deposition of basement membrane material in myxoid meningioma:
      immunohistochemical evidence for unbalanced production of type IV collagen and
      laminin.
AB  - Myxoid meningioma seen in a 25-year-old man is presented. Histologically, Leu 7
      positive meningotheliomatous tumor cells were embedded in the alcianophilic
      myxoid matrix. Characteristically, eosinophilic granular deposition was detected
      around the tumor cells and the boundary of tumor cells was not clearly defined.
      The pericellular deposits revealed the nature of the basement membrane with
      positive reactions by periodic acid-Schiff (PAS) sequence and immunostaining for
      type IV collagen, which is the major structural component of basement membrane.
      However, laminin, which is a non-collagenous glycoprotein of the basement
      membrane, was undetectable, and silver was not impregnated. Similar abnormal
      deposition of PAS-positive basement membrane-like material was observed in the
      myxoid stroma of a microcystic meningioma among 72 meningiomas additionally
      examined. The significance of the discrepant localization of immunoreactive type
      IV collagen and laminin is discussed.

PMID- 9589466
TI  - The first reported case of intestinal spirochaetosis in Japan.
AB  - A 65-year-old Japanese male consulted Ozuchi Prefectural Hospital (Iwate, Japan)
      on 19 January 1994 complaining of weight loss. Cecal mucosal biopsy material,
      which was stained with hematoxylin-eosin revealed a thick, basophilic fuzzy
      fringe covering the surface epithelium. Transmission and scanning electron
      microscopy observations demonstrated the presence of slightly wavy spirochaetes
      with tapered ends, which were attached to the surface epithelium of the colonic
      mucosa via one of these ends. The patient did not display any clinical symptoms
      of inflammatory bowel disease, and laboratory tests eliminated an
      immunodeficiency condition. Thus, in the present case, the intestinal
      spirochaetes appear to be harmless commensals. This paper presents the first
      reported case of intestinal spirochaetosis in Japan.

PMID- 9589467
TI  - Detection of circulating tumor cells in a patient with intravascular
      lymphomatosis: a case study examined by the cytology method.
AB  - Detection of circulating tumor cells in a patient with intravascular
      lymphomatosis (IVL) of the lung is reported. Peripheral blood cells were
      suspended in an isotonic sodium chloride solution, and red blood cells were
      lysed. The suspension was smeared on glass slides, fixed in 95% ethanol solution
      and stained using the Papanicolaou method. At the diagnosis of IVL, approximately
      65 tumor cells were detected in one smear preparation, which contained about 8 x
      10(5) nucleated cells. However, tumor cells disappeared from peripheral blood
      when those in the lung were eliminated by multiagent chemotherapy. Cytology
      examination of peripheral blood cells may be of assistance in the early diagnosis
      of IVL and in the assessment of therapeutic intervention.

PMID- 9589468
TI  - Epstein-Barr virus-associated Hodgkin's disease in HTLV-I seropositive patients:
      a report of two cases.
AB  - Diagnosis of Hodgkin's disease (HD) is quite difficult in the patient with
      seropositivity for human T cell lymphotropic virus I (HTLV-I). Herein, two cases
      of Epstein-Barr virus (EBV)-associated HD, which occurred in males with
      seropositivity for anti-HTLV-I, are reported. One patient is alive and was
      diagnosed as having interfollicular HD with CD20+CD15-CD30-CD3-CD4-CD8-CD45RO
      Read-Sternberg (R-S) cells. Positivity for EBV-encoded RNA 1 (EBER-1) and latent
      membrane protein 1 (LMP-1) was shown on follicular germinal center cells and R-S
      cells. In that case, neither T cell receptor (TCR) beta chain rearrangement nor
      integration of the HTLV-I provirus was demonstrated in the lymph nodes, although
      atyical lymphocytes (2%) were found in the peripheral blood. The other case
      pursued an aggressive clinical course and the patient was diagnosed as having an
      adult T cell leukemia/lymphoma (ATLL) because of the presence of anti-HTLV-I
      antibody, lymph node swelling, and the appearance of flower-like cells in the
      peripheral blood. However, an autopsy revealed no obvious ATLL cell infiltration
      in any of the organs examined. Multiple granulomatous lesions were found in the
      bone marrow, liver, kidneys, spleen, and lymph nodes. Reassessment of lymph node
      lesions in biopsies and granulomatous lesions in autopsy samples demonstrated
      that both lesions contained CD15+CD30+CD3-CD4-CD8-CD20-CD45RO-EBER-1+L MP-1+R-S
      cells, and they were considered to be a composite lymphoma of HD and ATLL. These
      two cases therefore suggest that EBV-associated HD can develop in patients with
      seropositivity for HTLV-I.

PMID- 9589469
TI  - Low-grade B cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a
      patient with rheumatoid arthritis.
AB  - The majority of thymic lymphomas are either lymphoblastic lymphoma, large B cell
      lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare.
      A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT)
      in the thymus is reported. A 55-year-old Japanese female with a history of
      rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was
      identified by computerized tomography and magnetic resonance imaging, and the
      thymus was resected through median sternotomy. The solid and nodular tumor had
      several small satellite extensions and was completely confined to within the
      thymus. Histologically, monotonous medium-sized centrocyte-like cells occupied
      the medulla of the thymus and infiltrated Hassall's corpuscles (lymphoepithelial
      lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a.
      IgA and kappa light chain restriction were also found in plasmacytoid cells in
      the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was
      demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type
      low-grade B cell lymphoma in the thymus. This is the first report of low-grade B
      cell lymphoma in the thymus associated with RA. As autoimmune diseases are known
      to be associated with lymphoid neoplasms, it is suggested that the RA played an
      important role in the development of malignant lymphoma in this case.

PMID- 9589470
TI  - Metastizing low-grade clear cell leiomyosarcoma of the uterus.
AB  - An unusual case of uterine clear cell tumor is reported in a 56-year-old woman.
      The neoplasm was identified as a peculiar low-grade leiomyosarcoma, composed
      mainly of watery, clear large cells with round, fairly regular nuclei. No
      appreciable pleomorphism or high mitotic activity was noted. There was no
      necrosis. The presence of occasional areas of transition between these cells and
      typical spindle leiomyosarcoma cells, together with the immunohistochemical
      results, allowed the recognition of a smooth muscle origin of this clear cell
      tumor. The patient was treated by hysterectomy. Six years later she developed an
      inguinal metastasis resembling an hibernoma, and then later developed a large
      retroperitoneal metastasis, which was composed entirely of clear cells and was
      distinguished from a liposarcoma by immunohistochemistry.

PMID- 9589471
TI  - Expression of KAI1 in paraffin-embedded normal, hyperplastic and neoplastic
      prostate and prostate carcinoma cell lines.
AB  - Expression of KAI1, a tumor metastasis suppressor gene, was studied with
      different fixatives in frozen and paraffin-embedded sections of human and rat
      prostate carcinoma cell lines and human prostate lesions by immunohistochemistry.
      Immunoreactivity of the membrane antigen in cell lines was associated with known
      expression levels in these lines and the fixative used. Formalin and
      paraformaldehyde helped maintain the immunoreactivity of cells. In human
      prostate, frozen sections revealed diffuse reactivity of the antigen in normal
      and neoplastic tissues while paraffin-embedded tissues usually showed focal
      reactivity, although more than 50% of cases with normal epithelium and
      adenocarcinomas were reactive. In some cases, pretreatment with trypsin enhanced
      immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense
      diffuse immunoreactivity, which suggested enhanced expression. Prostatic
      intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three
      of five metastases were reactive but two primaries and their metastases were not.
      Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in
      lymph nodes were immunoreactive, while adjacent primary or metastatic prostate
      adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded
      human tissues were not optimal for determining levels of expression of KAI1, they
      did show immunoreactivity that could have prognostic value and showed the
      specific cytoplasmic localization of the protein in cells.

PMID- 9589473
TI  - Cytofluorometric DNA analysis by stathmokinetic method of experimental thyroid
      neoplasms in rats.
AB  - Thyroid neoplasms were induced in rats by the intraperitoneal injection of N
      bis(2-hydroxy-propyl)nitrosamine as a carcinogenic substance and by the oral
      administration of KCIO4 as a promoter. The nuclear DNA content was measured in
      tissue sections of the tumors by the stathmokinetic method with the use of
      vincristine, and was correlated with the histopathological findings in the
      process of tumorigenesis and progression. Histological examination showed various
      types of lesions were produced in 47 surviving rats. A diploid pattern was seen
      in 82 (92%) of 89 tumors and an aneuploid pattern in 7 (8%) of 89 tumors.
      Papillary carcinomas and mixed carcinomas only had a diploid pattern, while two
      of 17 follicular carcinomas and five of 13 anaplastic carcinomas had an aneuploid
      pattern. On the other hand, benign proliferative nodules only had a diploid
      pattern. DNA heterogeneity was noted in seven malignant tumors. In four of them
      it was associated with the histopathological evidence of change, but in three
      there was no histological difference between the aneuploid and diploid areas
      other than a difference in the mitotic index. Mitotic indices were significantly
      higher in the aneuploid than in the diploid areas. These findings suggest that
      changes in the DNA ploidy cause histological abnormalities and/or affect the
      mitotic index. It is hypothesized that a change occurs in some diploid cells in a
      region of a tumor, and that aneuploid cells develop from the diploid cells which
      then acquire high proliferative activity.

PMID- 9589472
TI  - Immunohistochemical analysis of TrkA neurotrophin receptor expression in human
      non-neuronal carcinomas.
AB  - The Trk family of tyrosine protein kinase receptors plays a significant role in
      the development and maintenance of neural tissues. It has been recently shown
      that Trk receptors are also expressed by a wide range of normal non-neuronal
      tissues in humans in a cell type-specific manner. In the present study, the
      expression patterns of TrkA in 337 non-neuronal invasive carcinomas of 15
      different human tissues were investigated immunohistochemically. Overall, 133
      (39%), 101 (30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA
      immunoreactivity, respectively. Esophageal and thyroid carcinomas expressed high
      levels of TrkA, whereas the levels in gastric and colon cancers were low. TrkA
      expression was detected not only in carcinomas originating from TrkA-positive
      normal counterpart tissues, including the esophagus, breast, lung and uterus, but
      also in those from TrkA-negative tissues/cells of the thyroid, liver and ovary.
      Immunostaining for nerve growth factor-beta, the specific ligand for TrkA, in
      esophageal and breast carcinomas demonstrated its immunoreactivity in stromal
      fibroblasts and some TrkA-expressing tumor cells. These results suggest that
      paracrine/autocrine regulation via stromal/tumoral NGF-tumoral TrkA interaction
      may be involved in the growth of certain non-neuronal carcinomas.

PMID- 9589474
TI  - Vascular endothelial growth factor and neovascularization in astrocytic tumors.
AB  - It has been widely recognized that the vascular structure is an important factor
      when making a histopathological diagnosis and assessing the malignancy potential,
      especially of astrocytic tumors. The vascular endothelial growth factor (VEGF),
      which is thought to be regulated by the p53 gene, is a regulation factor for
      tumor neovascularization. The relationship between VEGF distribution and
      neovasculature was studied in 42 cases of astrocytic tumors (grades 1-4), which
      were obtained from surgical material, and the St Anne-Mayo grading system was
      applied. The relationship between the labeling indices (LI) of VEGF and LI of p53
      protein in tumor cells was also studied using immunohistochemistry. The VEGF LI
      in high-grade malignancy potential tumors, such as grade 3 and grade 4 tumors,
      was significantly higher than those that were low grade. In grade 4 tumors, a
      significant correlation between the VEGF LI and the proliferation indices of
      endothelial cells of neovasculatures was observed. No significant correlation was
      noted between p53 LI and VEGF LI, as well as p53 LI and histopathological grade.
      In astrocytic tumors, expression of VEGF may be correlated to tumor
      neovascularization, and can be considered as an indicator of malignancy potential
      in astrocytic tumors.

PMID- 9589475
TI  - Neuroepithelial and ependymal changes in HTX rats with congenital hydrocephalus:
      an ultrastructural and immunohistochemical study.
AB  - To investigate the pathogenesis of congenital hydrocephalus the brains of HTX
      rats aged between 16 days and 4 weeks and the brains of normal Wistar rats of the
      same ages were examined. In the fetal HTX rat brains, the lateral ventricles were
      symmetrically dilated from 20 days of gestation. The neuroepithelium bordering
      the ventricles showed thinning with cellular disarrangement and deformity.
      Similar neuroepithelial abnormalities were also found in the lateral ventricles
      of the HTX rat brain with no macroscopic signs of hydrocephalus at 20 days of
      gestation. The neuroepithelium showed flattening of the cells, widening of the
      intercellular spaces, formation of microvilli on the detached lateral cell
      surfaces, and frequent macrophage infiltration. On the other hand, the
      neuroepithelial cells of the third ventricle and the aqueduct were affected less
      severely or showed no significant abnormalities. Immunohistochemically, most of
      the neuroepithelium and ependyma of the lateral ventricles were positive for
      vimentin in both prenatal and postnatal hydrocephalic HTX rats, while a small
      number or none of those in normal control rats were positive. These morphological
      changes suggested that preferential involvement of the lateral ventricular
      neuroepithelium might be closely associated with the pathogenesis of congenital
      hydrocephalus in HTX rats.

PMID- 9589476
TI  - Genetic alterations in a patient with Turcot's syndrome.
AB  - Turcot's syndrome (TS) is a rare disorder associated with the development of both
      brain and colon neoplasms. Because of the very low incidence of the disease, its
      molecular basis remains unclear. Presented is a TS case of a 30-year-old Japanese
      male with a histopathologically confirmed diagnosis of both brain tumor
      (glioblastoma multiforme) and colon tumor (well-differentiated adenocarcinoma).
      Germline mutations of the p53 gene, somatic mutations of the Ki-ras, p53 and APC
      genes, and microsatellite instability (MSI) was examined using polymerase chain
      reaction (PCR)-single strand conformation polymorphism analysis, followed by PCR
      direct sequencing, and sequencing after subcloning. No germline mutations of the
      p53 gene were found. Somatic mutations of Ki-ras and APC genes were found in the
      colon adenocarcinoma but not in the brain tumor. No somatic mutation of the p53
      gene was present in either colon or brain tumors. Microsatellite instability of
      both colon and brain tumors was positive in two of four loci. These results
      indicate that the colon tumor of the TS patient carries the Ki-ras and APC gene
      mutations. The finding of MSI in both the brain and the colon tumors may support
      the hypothesis that alterations of DNA repair genes are involved in the tumor
      development of the TS patient.

PMID- 9589477
TI  - Transforming growth factor beta type II receptor (TGF beta RII) mutation in
      gastric lymphoma without mutator phenotype.
AB  - A new mutation in the serine-threonine kinase domain of the transforming growth
      factor beta type II receptor (TGF beta RII) was found in a case of diffuse, B
      cell non-Hodgkin's lymphoma of the stomach. A missense mutation (ACA to GCA, Thr
      to Ala) was detected in exon 5, and a wild type allele was also present. This is
      the first naturally occurring mutation in the kinase domain of this gene
      identified in human primary lymphoma. The replication error at three loci was
      negative, and the poly A tract of exon 3, which is frequently a target of
      mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the
      stomach is an addition to an expanding catalogue of tumors with TGF beta RII
      alterations, and the biological sequelae of the change in the functional domain
      and the clinical characteristics of the patient in this study are intriguing.

PMID- 9589478
TI  - Non-Hodgkin's lymphoma presenting with adrenal insufficiency and hypothyroidism:
      an autopsy case report.
AB  - A 55-year-old male presented with an initial manifestation of primary adrenal
      insufficiency, hypothyroidism. Computed tomography scans showed enlarged
      bilateral adrenal glands and thyroid. A pathological diagnosis of diffuse large
      cell, B cell lymphoma was made by a needle biopsy of the adrenal gland. He was
      treated with combination chemotherapy and adrenal and thyroid hormone
      replacement. The lymphoma subsequently involved the central nervous system. He
      died of pneumonia 8 months after the presentation of the first symptom. The
      postmortem examination demonstrated a complete regression of lymphoma in the
      bilateral adrenal glands and thyroid. This is an extremely rare case of
      coexistent lymphoma of the adrenal glands and the thyroid presenting with adrenal
      failure and hypothyroidism.

PMID- 9589479
TI  - Oligodendroglioma with signet-ring cell morphology: a case report with an
      immunohistochemical and ultrastructural study.
AB  - A case of oligodendroglioma with signet-ring cell (SRC) morphology arising in the
      right thalamic region in a 12-year-old boy is described. Histopathologically, the
      tumor was a composite neoplasm consisting of typical oligodendroglioma and
      anaplastic components with aggregates of SRC. Immunohistochemically the SRC were
      negative for glial fibrillary acidic protein (GFAP) but surrounded by GFAP
      positive anaplastic cells with high-grade nuclear features. Typical
      oligodendrogliomatous components were negative for GFAP. The Ki-67 labeling index
      evaluated with MIB-1 antibody was 1.3% in the SRC component, 9.2% in the GFAP
      positive anaplastic cell component, and 0.8% in the typical oligodendrogliomatous
      component. Ultrastructurally, the cytoplasm of the SRC was filled with
      irregularly and widely dilated cisternae of rough endoplasmic reticulum
      containing granular material. Intermediate filaments and a small number of other
      organelles were distributed in the perinuclear and peripheral areas. Both the SRC
      and anaplastic cells had slender cytoplasmic processes, although those of the SRC
      were short and few in number. These findings are distinct from those of SRC
      hitherto described in oligodendrogliomas to date, and suggest that there is a
      morphological heterogeneity in SRC rarely seen in oligodendrogliomas and that
      some examples of SRC are related to the anaplastic cells with astrocytic features
      in their origin.

PMID- 9589480
TI  - Ossifying renal tumor of infancy: the first Japanese case with long-term follow
      up.
AB  - Presented is the first Japanese case of ossifying renal tumor of infancy (ORTI),
      which is an extremely rare tumor and of which only nine cases have been reported
      in the literature. The patient was a four-month-old Japanese boy presenting as
      hematuria. A small nodular tumor (approximately 1 cm in size) protruded into the
      right pelvis from the superior caliceal region. Histologically the tumor
      originated from the tip of one medullary papilla and consisted of small rounded
      cells with a dense arrangement and several foci of minimally calcified osteoid
      lesions, including fewer but larger cells. Transition from the small to larger
      cells was suggested. The small cell only expressed vimentin, but the larger
      coexpressed vimentin, desmin, and epithelial membrane antigen. These findings
      suggested that the small cells differentiated to the larger cells with an
      epithelial nature associated somehow with osteoid formation. Embryonal metaplasia
      was assumed to occur in the collecting ducts entrapped by the tumor. The patient
      has been well without recurrence for more than 23 years. This is the longest
      survival period compared with other reported cases and confirms the benign nature
      of ORTI. It is absolutely crucial to make an accurate diagnosis of ORTI to avoid
      unnecessary treatment.

PMID- 9589481
TI  - Atypical decubital fibroplasia in a young patient with melorheostosis.
AB  - A case of atypical decubital fibroplasia of the right forearm arising in a 25
      year-old male with melorheostosis is presented. The diagnosis of melorheostosis
      involving the right-sided bones was made by radiographical studies, and the
      patient has been obliged to use crutches due to the contracture and limited range
      of motion of the right leg. Two painless masses occurred in the subcutis of the
      posterior aspect of the right forearm over the excrescences of the underlying
      ulna due to melorheostotic deformity. Grossly, ill-defined firm masses, which
      measured 3 x 6 x 1.5 cm and 4 x 5 x 1 cm, respectively, were white and
      intermingled with yellow fatty tissue. Histologically, the lesions consisted of a
      proliferation of plump fibroblastic cells with abundant collagenous stroma.
      Vascular proliferation and occasional eosinophilic degeneration of the collagen
      fibers were also seen. The gross and histological features were those of atypical
      decubital fibroplasia (ischemic fasciitis). Immunohistochemically, the plump
      fibroblastic cells were positive for vimentin, but negative for desmin, muscle
      specific actin, and alpha-smooth muscle actin. Chondroid metaplasia was focally
      noted and round-shaped cells within this area were positive for S-100 protein.
      This lesion seemed to be a fibroblastic response against the long-standing,
      intermittent ischemia of the subcutaneous tissue between the bony excrescences
      due to melorheostosis and the weight-bearing forces of the crutch.

PMID- 9589482
TI  - Endovascular papillary angioendothelioma (Dabska tumor) in an elderly woman.
AB  - A patient with endovascular papillary angioendothelioma with a low grade of
      malignancy showing papillary proliferation of endothelioid cells is presented.
      The patient, an 83-year-old woman, underwent resection of a tumor of the neck. At
      operation a 9 x 7 cm cystic tumor containing yellow transparent liquid with clots
      was found in the subcutaneous tissue. Histological studies showed endothelioid
      cells with spindle-shaped nuclei proliferated in layers around the fibrovascular
      cores, which showed the characteristic appearance of papillary proliferation.
      These cells were immunohistochemically positive for CD31, CD34 and factor VIII
      related antigen. Based on these observations, the tumor was considered to be an
      endovascular papillary angioendothelioma (Dabska tumor). Dabska tumor is a
      vascular tumor with a low grade of malignancy and usually occurs in infants and
      young children. About 13 cases of Dabska tumor have been reported. The occurrence
      of a Dabska tumor in an aged patient is considered to be rare.

PMID- 9589483
TI  - Recommendations for the reporting of tissues removed as part of the surgical
      treatment of cutaneous melanoma. Association of Directors of Anatomic and
      Surgical Pathology.
AB  - The Association of Directors of Anatomic and Surgical Pathology have developed
      recommendations for the surgical pathology report for common malignant tumors.
      The recommendations for cutaneous melanoma are reported herein.

PMID- 9589484
TI  - Expression of carbohydrate antigens, p80NPM/ALK, cytotoxic cell-associated
      antigens, and Epstein-Barr virus gene products in anaplastic large cell
      lymphomas.
AB  - The expression of carbohydrate antigens, including sialyl Lewis X (SLEX) and BNH9
      antigen, the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion protein
      (p80NPM/ALK), cytotoxic cell-associated antigens, and Epstein-Barr virus (EBV)
      gene products in CD30+ anaplastic large cell lymphoma (ALCL) was investigated by
      immunohistochemistry and in situ hybridization (ISH) methods. The expression of
      SLEX and BNH9 antigen in ALCL was examined using CSLEX1 and BNH9, which
      specifically react with SLEX and oligosaccharides (H and Y haptens),
      respectively. SLEX was expressed in seven of 12 ALCL and BNH9 was positive for
      five of 12 ALCL. With respect to the relationship between SLEX and BNH9
      expression in ALCL, some ALCL expressed both antigens, which suggests that they
      might have an increased or preserved activity of glycosyltransferase that is
      responsible for the synthesis of the type I or type II core sequences, although
      other ALCL expressed either SLEX or BNH9. To detect p80NPM/ALK in ALCL, the
      sections were immunostained with an anti-p80 antibody. Three of 12 ALCL expressed
      the NPM/ALK-encoded p80 protein. All three ALCL positive for p80NPM/ALK expressed
      SLEX and two of them were stained with BNH9, which raised the possibility that
      p80 overexpression may be involved in the aberrant expression of type I or type
      II chains with varying degrees of fucosylation or sialylation. While the
      expression of cytotoxic cell-associated antigens such as CD8, CD56 and T cell
      intercellular antigen 1 (TIA-1) in ALCL was immunohistochemically examined, none
      of the 12 ALCL expressed CD56 and only one case expressed CD8. TIA-1 was
      expressed in seven of 12 ALCL. Four of five BNH9-positive cases expressed TIA-1,
      suggesting that BNH9-positive cases tended to have TIA-1. In situ hybridization
      studies using an EBV-encoded RNA-1 (EBER-1) probe were performed on 12 ALCL to
      detect EBV in the lymphoma cells. EBER-1 signals were detected in the small
      lymphocytes but not in the lymphoma cells of two ALCL. However, latent membrane
      protein 1 immunoreactivity was found in one case. These results appear to
      indicate that there is no strong association between EBV and ALCL.

PMID- 9589485
TI  - How thick are the paraffin-embedded tissue sections routinely prepared in
      laboratory? A morphometric study using a confocal laser scanning microscope.
AB  - In order to evaluate the differences between cut and measured thicknesses of
      formalin-fixed, paraffin-embedded tissue sections, formalin-fixed, paraffin
      embedded blocks of liver tissue were prepared from four male Wistar rats. The
      sections were cut at preselected thicknesses of 3, 6, 9, 12, 15 and 18 microns,
      and observed under confocal laser scanning microscopy. The maximum and minimum
      section thicknesses were measured using a vertically cut section image
      constructed by the software incorporated in the microscope. The surface of the
      section was not smooth but showed fine undulations in addition to a slight
      inclination. The mean and range of the section thicknesses measured were 4.3 +/-
      1.3, 7.0 +/- 1.7, 9.8 +/- 2.1, 12.0 +/- 2.6, 14.1 +/- 3.0, and 17.7 +/- 3.8
      microns for the preselected cut thicknesses of 3, 6, 9, 12, 15 and 18 microns. It
      is stressed that the evaluated parameters of the section (volume or surface
      densities) include standard errors of up to 10% caused by the differences between
      the cut and real thicknesses.

PMID- 9589486
TI  - Expression of splice variants of CD44 in thyroid neoplasms derived from
      follicular cells.
AB  - Isoform expression of CD44 in follicular carcinoma (FC) of the thyroid was
      analyzed by immunohistochemical staining and compared to the isoforms in
      follicular adenoma (FA) and papillary carcinoma (PC) of the thyroid. Variant
      isoforms of CD44 (CD44v) were detected in these neoplastic cells but not in non
      neoplastic cells. CD44v6 was expressed in PC with nodal metastasis and also in FC
      at significantly higher frequencies than those in PC without metastasis and FA.
      The frequency of expression of CD44v3 was significantly higher in PC with nodal
      metastasis than in PC without metastasis. The reverse transcription-polymerase
      chain reaction (RT-PCR) followed by Southern blotting analysis revealed the
      presence of a transcript for a variant of CD44 that contained variant exon 6 in
      FA, FC and PC. DNA sequencing of the products of RT-PCR yielded three species of
      cDNA for CD44v. One of the cDNA corresponded to a transcript that contained
      variant exon 6. These results suggest that immunohistochemical staining and RT
      PCR with Southern blotting analysis for CD44v6 might be a useful diagnostic tool
      for the differentiation of FC from FA and that the expression of CD44v3 and
      CD44v6 might be important for the development of nodal metastasis in cases of PC.

PMID- 9589487
TI  - The Quilty lesion enigma: focal apoptosis/necrosis and lymphocyte subsets in
      human cardiac allografts.
AB  - Quilty lesions, as first described by Billingham in 1981, or 'Quilty Effect' (QE)
      are distinct endomyocardial mononuclear cell infiltrates that have been observed
      in human heart transplant recipients, as well as in experimental models of heart
      transplantation. In the present investigations, the pattern and extent of
      apoptosis (programmed cell death) and myocyte necrosis, as well as specific
      lymphocyte subsets in Quilty lesions was assessed. Endomyocardial biopsies
      obtained from 13 patients at 10-3362 days post-transplant were examined.
      Apoptosis, as identified by DNA nick end-labeling, was found in myocytes at the
      periphery of Quilty lesions in 11 of 13 cases (85%), and 'early' stages of
      myocyte necrosis, as demonstrated by specific staining with alpha light chain
      myosin monoclonal antibodies (mAb), was observed at the same sites in 10 of 13
      cases (77%) of both Quilty type A and type B lesions. Apoptosis was not
      identified in the lymphocyte infiltrates of any of the lesions examined.
      Lymphocyte subsets were characterized using mAb for T cell receptor (CD3), for
      helper/inducer T cells (CD4), for cytotoxic/suppressor T cells (CD8) and for
      mature B cells (CD20). Immunostaining revealed separate clusters of T lymphocytes
      with less prevalent B cells within the Quilty lesions. CD4+ cells were found in
      larger numbers than CD8+ cells in all cases. Non-B, non-T large lymphocytes were
      occasionally present. Except for the extent of the cellular infiltrate, no major
      cytochemical lymphocyte distribution differences were found between Quilty type A
      and B lesions. Myocyte apoptosis and early necrosis at the periphery of Quilty
      lesions suggest that early myocyte injury occurring in B lesions may represent
      initial or 'abortive stages' of cardiac allograft rejection. Why these lesions do
      not progress to overt rejection indeed warrant further detailed studies.

PMID- 9589488
TI  - Time-specific action of N-methyl-N-nitrosourea in the occurrence of retinal
      dysplasia and retinal degeneration in neonatal mice.
AB  - The morphologic response of neonatal mouse retina to the alkylating agent N
      methyl-N-nitrosourea (MNU) was examined at different periods of retinal
      development. A dose of 60 mg/kg N-methyl-N-nitrosourea was injected
      intraperitoneally to neonatal C57BL mice at 0, 3, 5, 8, 11, 14, 17, and 20 days
      of age and to C3H mice at 0 days of age, and the retinas were examined
      sequentially. In the C57BL mice, MNU evoked a time-dependent occurrence of
      retinal dysplasia and retinal degeneration. With MNU treatment at day 0 and day 3
      (the stage of retinal cell proliferation), retinal dysplasia characterized by the
      progressive disorganization of neuroblasts, which led to the formation of
      rosettes, was found in the outer neuroblastic/nuclear layer above the normal
      pigment epithelial cells during days 8-20, but decreased at day 50. The rosettes
      were surrounded by photoreceptor segments and Muller cell processes, and by
      photoreceptor nuclei. The MNU response was related to retinal differentiation;
      following MNU treatment at day 5 or 8 (the stage of retinal cell differentiation)
      the cells were much less sensitive (i.e. no retinal response was found). However,
      with MNU treatment at days 11, 14, 17, and 20 (after cellular differentiation),
      retinal degeneration characterized by selective photoreceptor apoptosis was seen.
      These results suggest that there is a critical period for the time of MNU
      administration in the development of mouse retinal lesions. In C3H (rd/rd) mice,
      MNU treatment at day 0 resulted in retinal degeneration with only slight rosette
      formation at the peripheral retina.

PMID- 9589489
TI  - A novel marker of Schwann cells and myelin of the peripheral nervous system.
AB  - Cellular markers are useful in the immunohistochemical studies of normal and
      pathological tissues. Herein, the development of a monoclonal antibody,
      Schwann/2E, which reacts with Schwann cells and myelin of the peripheral nervous
      system (PNS) is described. The Schwann/2E antibody was secreted by a hybridoma of
      mouse myeloma cells and mouse spleen cells that were immunized in vivo with a
      cytoskeletal fraction of the human spinal nerve. This antibody immunostained
      formalin-fixed, paraffin-embedded human, rat, and mouse tissue by the indirect
      immunoperoxidase method. Schwann cells and myelin of the PNS were intensely
      labeled by the Schwann/2E antibody. Both the nuclei and cytoplasm of the Schwann
      cells were labeled. As shown by a comparative light and an electron microscopic
      study, the Schwann/2E antibody immunoreacted with the Schwann cells that had
      myelinated axons, but not with those that had unmyelinated axons. The endoneurial
      fibroblast was not immunolabeled. This antibody slightly stained the endothelial
      cells of the lung and kidney. Myelin and oligodendroglia of the central nervous
      system did not react with the Schwann/2E antibody. The Schwann/2E antigen was
      stable in several histological fixatives. These results indicate that, under
      normal and pathological conditions, the Schwann/2E antibody could be a useful
      immunohistochemical marker of Schwann cells and myelin of the PNS.

PMID- 9589490
TI  - Prediction of efficacy of interferon treatment of chronic hepatitis C by
      multivariate analysis and a new classification.
AB  - One hundred and fifteen patients with chronic hepatitis C were administered
      interferon (IFN) and classed into two groups: (i) complete responders (CR), HCV
      RNA continuously negative 1 year after treatment; and (ii) non-responders (NR),
      positive 1 year after treatment. Multivariate analysis comprised eight variables:
      age, sex, transfusion history, alanine aminotransferase level, viral genotype,
      level of viremia, type of IFN, and total amount of IFN. The HCV-RNA level was
      correlated with complete response (P = 0.0175). Liver biopsy specimens were
      classified into four grades and stages according to the measure of severity and
      the extent of fibrosis, respectively. There was no correlation between the
      efficacy rate and grading. However, in staging there was a difference in the
      efficacy of IFN between stages 1 or 2, and stage 3 (0.05 < P < 0.1 and 0.01 < P <
      0.025, respectively). Of the CR patients, 0% (0/5) were at stage 0 (no fibrosis);
      27.5% (22/80) at stage 1 (mild); 42.9% (6/14) at stage 2 (moderate); and 6.3%
      (1/16) at stage 3 (severe fibrosis). Thus the new classification would be useful
      in predicting roughly the efficacy of IFN.

PMID- 9589491
TI  - Adult T cell leukemia/lymphoma with massive involvement of cardiac muscle and
      valves.
AB  - An autopsy case of a 58-year-old woman with massive cardiac involvement of adult
      T cell leukemia/lymphoma (ATLL) is reported. She developed cardiac failure due to
      aortic and mitral regurgitation with cardiac infiltration of ATLL cells, and
      underwent replacement of both aortic and mitral valves. Studies of the cut
      surfaces revealed diffuse thickening of the subendocardial wall of the left
      chamber with widespread whitish-brown tumor infiltrates. In the regions
      surrounding the replaced aortic and mitral valves there was also massive tumor
      cell infiltration. The tumor cells infiltrating the cardiac muscle wall were T
      cell in origin and exhibited Leu-3a (CD4)-positive immunoreaction.
      Ultrastructurally, tumor cells contained markedly indented nuclei and some were
      attached directly to the muscle cells. These findings suggest that this was an
      unusual form of ATLL with widespread involvement of the heart.

PMID- 9589492
TI  - Primary hepatic malignant fibrous histiocytoma: report of a case and review of
      the literature.
AB  - Malignant fibrous histiocytoma (MFH) is a common sarcoma of adulthood, frequently
      arising in the extremities, but also in the abdomen and the retroperitoneum.
      Primary MFH of the liver, however, remains extremely rare and is one of the least
      diagnosed primary hepatic sarcoma. Another case of primary MFH of the liver is
      reported. The patient presented with a 12 cm mass involving the right and left
      lobes of the liver. The histopathologic examination revealed a typical MFH
      swirling (storiform) pattern composed of atypical spindle and giant cells. The
      radiologic, histologic, and clinical behavior of this rare neoplasm are reviewed.

PMID- 9589493
TI  - Juvenile hyaline fibromatosis: a report of two unrelated adult sibling cases and
      a literature review.
AB  - Two unrelated adult sibling cases (36- and 32-year-old females) of juvenile
      hyaline fibromatosis are presented. The parents of one of these patients were non
      consanguineous but natives of a small island, and one elder sister among four
      siblings was affected with the same disease. The parents of the other patient
      were consanguineous, and one other sibling suffered from the identical disease.
      Both patients presented with multiple subcutaneous nodules, which they had had
      since infancy, and had undergone numerous surgical excisions. Light microscopy
      examination of skin lesions from both patients showed identical histology; an
      abundance of a homogenous, amorphous, eosinophilic extracellular matrix in which
      spindle-shaped cells were embedded. Electron microscopically, the spindle-shaped
      cells had hypertrophic Golgi apparatus and dilated, rough endoplasmic reticulum.
      Fine fibrillar and granular material-filled structures, the contents of which
      were occasionally released into the extracellular matrix, were also seen.
      Immunohistochemically, the spindle-shaped cells were vimentin-positive but
      negative for alpha-smooth muscle actin and S-100 protein, and the hyaline ground
      substance was positive for type I and type III collagen but negative for type II
      and type IV collagen and tenascin. Matrix metalloproteinase-1, -2, and -9, and
      tissue inhibitor of matrix metalloproteinase (TIMP)-2 was positive but TIMP-1 was
      negative. A review of 39 cases of juvenile hyaline fibromatosis in the literature
      is also presented. In summary, skin lesions may be the most outstanding symptoms
      of juvenile hyaline fibromatosis, but joint contracture and gingival hypertrophy
      precede the skin manifestation.

PMID- 9589494
TI  - Microvenular hemangioma.
AB  - A case of microvenular hemangioma in a 23-year-old Japanese female is described.
      The patient presented with a slowly growing, solitary reddish plague on her back,
      which measured 15 x 17 mm. Histologically, the tumor was an infiltrative growth
      throughout the dermis. It consisted of thin-walled, small-sized, irregularly
      branched vascular vessels. The vascular lumina were narrow. The flattened
      endothelial cells had oval to spindle-shaped nuclei and scant cytoplasm that were
      immunohistochemically positive for endothelial markers. The tumor cells lacked
      cellular atypia, pleomorphism, and mitotic figures. The patient was well without
      disease 8 months after the excision. Pathologists and clinicians should be aware
      of the existence of this type of hemangioma with an infiltrative growth and avoid
      overdiagnosis and overtreatment.

PMID- 9589495
TI  - Gastric metastasis from breast cancer: a pitfall in gastric biopsy specimens.
AB  - A 49-year-old woman presented with abdominal discomfort and weight loss.
      Gastroduodenoscopy showed small polypoid lesions and biopsy specimens suggested
      primary adenocarcinoma with neuroendocrine differentiation. As the patient had a
      prior history of metachronous breast cancer, it was concluded that the case was
      metastatic carcinoma from the breast. The usefulness of a panel of selected
      immunohistochemical markers to determine the primary site of the breast in an
      appropriate clinical setting is greatly emphasized.

PMID- 9589496
TI  - Localized accumulation of Russell body-containing plasma cells in gastric mucosa
      with Helicobacter pylori infection: 'Russell body gastritis'.
AB  - One of the gastric biopsy specimens taken from a 53-year-old male showed
      localized accumulation of plasma cells containing Russell bodies, in association
      with infection of Helicobacter pylori (H. pylori). An endoscopic study
      demonstrated multiple ulcer scars in the antrum. Immunohistochemically, H. pylori
      infection was identified both on the surface of the foveolar epithelial cells and
      in the cytoplasm of macrophages in the lamina propria mucosae. Plasma cells
      filled with 'Russell bodies', so-called 'Motts cells', were immunoreactive for
      CD45, CD79a and IgG. This seems to be a previously unrecognized tissue reaction
      in gastric mucosa associated with H. pylori infection, which we have called
      'Russell body gastritis'.

PMID- 9589497
TI  - A pediatrician's view.

PMID- 9589498
TI  - Helping the pediatrician understand and survive in managed care: an introduction.

PMID- 9589499
TI  - Pediatric perspective on the changing healthcare delivery system.

PMID- 9589500
TI  - An introduction to the National Committee for Quality Assurance.
AB  - The corporations that purchase private health benefits and the public payers,
      Medicare and Medicaid, are insisting increasingly that managed care plans be
      publicly accountable for the quality of care and service delivered. NCQA has
      responded to that demand with programs that assess both the organization and
      operation of the plan and the results that the plan actually achieves. Although
      our capacity to evaluate managed care is still incomplete, an increasingly
      complete picture of quality in managed care is emerging. We see evidence already
      that the capacity is driving improvement, and we hope that our work will mean
      that practicing physicians will find themselves better able to deliver the
      highest quality care possible to children in America.

PMID- 9589501
TI  - The fundamentals of pediatric patient and disease management.

PMID- 9589502
TI  - Legal issues in managed care: the pediatrician's perspective.

PMID- 9589503
TI  - Pediatric guidelines and managed care: who is using what and what difference does
      it make?

PMID- 9589504
TI  - Changing pediatric practice in a changing medical environment: factors that
      influence what physicians do.

PMID- 9589505
TI  - A structural model of the relationships among stage of disease, age, coping, and
      psychological adjustment in women with breast cancer.
AB  - The present study used structural equation modeling to examine the relationships
      among disease stage (i.e. Stage II versus Stage IV), age, coping style, and
      psychological adjustment in 100 women diagnosed with breast cancer. Five separate
      models were examined: a full model, a mediational model, a demographic-disease
      model, a coping style model, and a regression model The analyses revealed that
      the present data best fit the mediational model in which age and stage of disease
      were not directly associated with psychological adjustment but, instead, were
      mediated by coping style (chi 2(25) = 45.776, AASR = 0.05, CFI = 0.94). The
      mediational model accounted for 56% of the variance in psychological adjustment.
      In particular, the model showed that younger women and women with an earlier
      disease stage used greater levels of the coping strategy characterized as a
      fighting spirit and lower levels of the coping strategies characterized as
      hopelessness/helplessness, anxious preoccupation, and fatalism which, in turn,
      were related to better psychological adjustment. Overall, these findings may
      offer an explanation for the conflicting findings regarding the relationship
      between age, stage of disease, and psychological adjustment to breast cancer by
      illustrating that coping strategies may be an essential mediating factor; in
      turn, a mediating model of psychological adaptation may offer useful information
      for clinicians as they implement interventions designed to improve patients
      coping efforts.

PMID- 9589506
TI  - The application of cognitive-behavioural therapy for depression to people with
      human immunodeficiency virus (HIV) and acquired immune deficiency syndrome
      (AIDS).
AB  - Over the past decade the cognitive approach to depression has received
      considerable attention. The impetus for this stems from empirical and theoretical
      reports of its efficacy in its application to the treatment of depressed
      individuals (Beck, 1976, 1976; Seligman, 1975; Abramson et al., 1978). This paper
      examines the theory and practice of cognitive behavioural therapy (CBT) and
      questions whether it has anything to offer clinicians working with people
      affected by acquired immune deficiency syndrome (AIDS) or the human
      immunodeficiency virus (HIV) given that it was originally developed, and has
      traditionally been used, to treat mood disordered psychiatric patient
      populations. The theory of cognitive therapy is examined with specific emphasis
      on Beck's contribution. Reference is made to the literature on the psychological
      problems experienced by people with AIDS (PWAs), and an assessment is presented
      of the contribution of cognitive therapy to ameliorate problems experienced by
      PWAs.

PMID- 9589507
TI  - Intrusiveness of illness and quality of life in young women with breast cancer.
AB  - Our objective was to test a theoretical model that explains quality of life as a
      function of the intrusiveness of illness encroaching on the different domains of
      one's life. The intrusiveness of illness is explained not only by disease and
      treatment related factors, but also by one's psychological and social resources
      (Devins, 1994). To investigate this issue, a sample of 336 women aged 50 and
      under, recently diagnosed with breast cancer were interviewed in their homes.
      Consistent with Devins' model, intrusiveness of illness mediated the effect of
      disease and treatment factors on quality of life. Contrary to his model, some
      treatment factors also had direct effects while social and psychological factors
      had only direct effects on quality of life. Neither time post-diagnosis nor type
      of treatment affected the psychological component of quality of life.

PMID- 9589508
TI  - Social support, life stress, pain and emotional adjustment to advanced breast
      cancer.
AB  - The purpose of this study was to examine relationships between emotional
      adjustment to advanced breast cancer, pain, social support, and life stress. The
      cross-sectional sample was compromised of 102 women with metastatic and/or
      recurrent breast cancer who were recruited into a randomized psychosocial
      intervention study. All women completed baseline questionnaires assessing
      demographic and medical variables, social support, life stress, pain, and mood
      disturbance. Three types of social support were assessed: (1) number of persons
      in support system; (2) positive support; and (3) aversive support. On the Profile
      of Mood States (POMS) total score, we found significant interactions between life
      stress and social support; having more people in the patient's support system was
      associated with less mood disturbance, but only among patients who had undergone
      greater life stress. Also, aversive social contact was significantly related to
      total mood disturbance (POMS), and having more aversive social contact was
      particularly associated with total mood disturbance (POMS) among patients who had
      undergone greater life stress. Pain intensity was associated with greater total
      life stress, and was not significantly related to social support. These results
      are consistent with the 'buffering hypothesis' that social support may shield
      women with metastatic breast cancer from the effects of previous life stress on
      their emotional adjustment; however, aversive support may be an additional source
      of life stress associated with emotional distress. Also, pain is greater among
      women with greater life stress, regardless of social support.

PMID- 9589509
TI  - Depressive disorders in an out-patient oncology setting: prevalence, assessment,
      and management.
AB  - OBJECTIVE: To assess the prevalence of depressive disorders among cancer patients
      attending the out-patient oncology clinic of a major hospital, and to initiate
      the development of a valid and practical psychological morbidity screening
      instrument suitable for local conditions. DESIGN: Survey utilising self-report
      screening scales and full psychiatric interviews. SETTING: Radiotherapy
      department, Groote Schuur Hospital. PATIENTS: Breast cancer, head and neck
      cancer, and lymphoma patients attending out-patient oncology clinics. RESULTS: A
      total of 456 patients completed the Hospital Anxiety and Depression Scale (HADS).
      Of that sample, 245 also completed the Beck Depression Inventory (BDI), and 100
      were subjected to a structured psychiatric interview. The prevalence of
      depression in this population is approximately 14%, which is lower than estimates
      reported elsewhere. Only 14% of the interviewed depressed cases had been
      identified and treated by the existing health care system, highlighting the need
      for suitable screening tools. Appropriate screening tools and management
      strategies for this population are discussed. CONCLUSION: This study highlighted
      the need for routine screening for depression and the implementation of cost
      effective management strategies in oncology settings.

PMID- 9589510
TI  - Psychological support to an autologous bone marrow transplant unit in a community
      hospital: a pilot experience.
AB  - Autologous Bone Marrow Transplantation (AuBMT) has emerged as an efficacious
      treatment for certain hematological and solid tumors. Some of the complications
      of allogeneic transplants are avoided with an autologous transplant. Due to the
      decreased toxicity of this procedure, AuBMT can be administered at a community
      hospital where the setting is less burdensome for patients and families. The
      latter can continue to provide support for the patient as relocation is not
      necessary and visiting is easier. This report is a case analysis of the first 30
      patients to undergo an autologous transplant as a pilot study in such an
      environment. This pilot project--done in a community hospital in Connecticut--may
      provide cost effective, high quality care in a more personal environment in the
      patient's own community. The different neoplastic diagnoses are listed as well as
      the types of psychological interventions available for these patients. Two case
      studies are described for clinical illustration. A discussion presents how psycho
      oncology can assist the multidisciplinary team.

PMID- 9589511
TI  - Stress associated with asbestosis: the trauma of waiting for death.

PMID- 9589512
TI  - Sertraline relieves hot flashes secondary to medical castration as treatment of
      advanced prostate cancer.

PMID- 9589513
TI  - Comment on Weitzner and Meyers.

PMID- 9589514
TI  - The membrane phospholipid hypothesis as a biochemical basis for the
      neurodevelopmental concept of schizophrenia.
AB  - The neurodevelopmental hypothesis of schizophrenia is becoming an important
      feature of research in the field. However, its major drawback is that it lacks
      any biochemical basis which might draw the diverse observations together. It is
      suggested that the membrane phospholipid hypothesis can provide such a
      biochemical basis and that the neurodevelopmental phospholipid concept offers a
      powerful paradigm to guide future research.

PMID- 9589515
TI  - Reversal of cerebral asymmetry in schizophrenia measured with
      magnetoencephalography.
AB  - It has been suggested that schizophrenic patients fail to develop left-hemisphere
      dominance because of an early disturbance in neuronal development. This
      hypothesis has been supported by some post-mortem. CT and magnetic resonance
      imaging (MRI) studies, while other in-vivo studies have given contradicting
      results. We used 122-channel whole-head magnetoencephalography and MRI to locate
      the sources of auditory evoked responses in 19 schizophrenic patients and in 20
      healthy controls. Auditory evoked responses were detected in all subjects. The
      left-right hemisphere asymmetry of cerebral sources for auditory evoked responses
      was markedly dispersed among patients when compared with controls. The source
      locations for left auditory cortex were clearly anterior with respect to the
      right hemisphere in 32% of the patients, while the corresponding prevalence of
      this abnormal asymmetry was 0% in controls (p = 0.008. Fisher's exact test). The
      reversed asymmetry appeared to be associated with a shorter anterior-posterior
      distance between the auditory cortex and the anterior tip of the temporal lobe in
      the left side when compared with the right side. The reversed asymmetry was
      associated with higher PANSS general psychopathological score, and especially
      with higher guilt feelings and motor retardation scores. The large 2.5-fold
      standard deviation in the inter-hemispheric anterior posterior difference in the
      location of the auditory cortex among patients (p 0.001 for the difference in the
      magnitude of variance between controls and patients) clearly reflects the
      dispersion of the left right asymmetry into both direction, and three of the
      patients with 'normal asymmetry' had a greater left-right asymmetry than any of
      the controls. Markedly greater reversal of hemispheric asymmetry among patients
      implies that regulation of the development of brain asymmetry is disturbed among
      schizophrenic patients. Abnormality in the cerebral asymmetry may be a crucial
      factor in the development of schizophrenic disorder in a substantial proportion
      of patients. The results suggest that the reversed asymmetry is associated with
      the higher severity of general psychopathological symptoms.

PMID- 9589516
TI  - Differences in the EEG profiles of early and late responders to antipsychotic
      treatment in first-episode, drug-naive psychotic patients.
AB  - The aim of this study was to search for differences in the EEG of first-episode,
      drug-naive patients having a schizophrenic syndrome which presented different
      time courses in response to antipsychotic treatment. Thirteen patients who
      fulfilled DSM-IV diagnosis for schizophrenia or schizophreniform disorder
      participated in this study. Before beginning antipsychotic treatment, the EEG was
      recorded. On the same day psychopathological ratings were assessed using the
      ADMDP system, and again after 7 and 28 days of treatment. The resting EEG (19
      leads) was subject to spectral analysis involving power values for six frequency
      bands. The score for the schizophrenic syndrome was used to divide the patients
      into two groups: those who displayed a clinically meaningful improvement of this
      syndrome (reduction of more than 30%) after 7 days of treatment (early
      responders, ER) and those who showed this improvement after 28 days (late
      responders. LR). Analysis of variance for repeated measures between ER, LR and
      their matched controls with the 19 EEG leads yielded highly significant
      differences for the factor group in the alpha2 and beta2 frequency band. No
      difference was found between the slow-wave frequency bands. Compared to controls
      the LR group showed significantly higher alpha2 and beta2 power and, in
      comparison to the ER group, significantly higher alpha2 power. There were no
      significant differences between the ER and the control group. These findings
      point to differences in brain physiology between ER and LR. The implications for
      diagnosis and treatment are discussed.

PMID- 9589517
TI  - Neurological abnormalities in schizophrenia: clinical, etiological and
      demographic correlates.
AB  - An increased rate of neurological abnormality (NA) is typically observed in
      samples of schizophrenic patients, but the origin and relevance of the NA remain
      unclear. To investigate this further, relationships were studied between the
      patient's degree of NA and a range of clinical, putative etiological and
      demographic characteristics among 60 patients with schizophrenia who had
      previously been shown to have an elevated rate of NA. No significant
      relationships were found between NA and demographic, etiological or most clinical
      history characteristics, including past and current neuroleptic exposure.
      However, an increased rate of NA was significantly related to current poor global
      functioning. In total, the findings suggest that NA may represent one
      manifestation of an early and rather stable disease process, with an additional
      fluctuating clinically related component.

PMID- 9589518
TI  - Neuropsychological deficits associated with schizophrenic syndromes.
AB  - A battery of computerised tests and the classical Stroop test were administered
      to a group of 56 patients with DSM-III-R schizophrenia and 17 controls to explore
      the nature of the mental processes associated with the psychomotor poverty and
      disorganisation syndromes. In patients with persistent illness, psychomotor
      poverty was associated with slower responses in a two-choice guessing task in
      which the appropriate response was not dictated by the circumstances. This
      association was not observed in patients with remitting illness, providing
      neuropsychological support to the distinction between 'negative' and 'deficit'
      symptoms in schizophrenia. Disorganisation syndrome was associated with impaired
      performance in the classical Stroop test, as shown in previous studies, but not
      with impairment in a task which required suppression of processing of irrelevant
      aspects of a stimulus, nor with impairment in a task which required the
      suppressing of a primed but irrelevant non-verbal response. This suggests that
      the disorganisation syndrome might be associated with a specific difficulty in
      suppressing irrelevant verbal responses.

PMID- 9589519
TI  - The effects of an early stressful life event on sensorimotor gating in adult
      rats.
AB  - There is increasing evidence that patients suffering from schizophrenia have
      disturbances in the brain and other parts of the body indicative of a disturbed
      development. These findings have led to the so-called neurodevelopmental
      hypotheses of schizophrenia, which state that schizophrenia (or a predisposition
      for this disease) results from perinatal disturbances which affect the normal
      development of the central nervous system. In order to study such a possible
      relationship we have used early short-lasting (24 h) maternal deprivation, and
      studied the influence of this life event on prepulse inhibition of the acoustic
      startle at adult age in rats, since it has been shown that schizophrenic patients
      show a disruption of prepulse inhibition. The results show that early maternal
      deprivation significantly reduced prepulse inhibition when the animals were
      tested at postnatal day (pnd) 69 (birth being pnd 0). The effects were
      qualitatively similar when deprivation took place on pnd 3, 6 or 9, although at
      the later days the effects were stronger. There was little influence on baseline
      startle response (except for a small reduction seen after deprivation on pnd 6).
      In separate experiments it was shown that the effect of maternal deprivation on
      prepulse inhibition was not seen before puberty and was similar for male and
      female offspring. Moreover, the effects could be reversed by treatment with the
      classical antipsychotic, haloperidol, or the putative atypical antipsychotic,
      quetiapine (both given 15 min before the prepulse inhibition experiment). In
      summary, the results show that an early stressful life event can have a delayed
      influence on prepulse inhibition in rats, qualitatively similar to the
      disturbances seen in schizophrenic patients. These data suggest that maternal
      deprivation (i.e., a 24 h separation of rat pups from their mother early in life)
      may represent an interesting animal model for investigating the influence of
      early life events on the information processing and general functioning of an
      individual at adult age.

PMID- 9589520
TI  - Walking with the advanced reciprocating gait orthosis (ARGO) in thoracic
      paraplegic patients: energy expenditure and cardiorespiratory performance.
AB  - The aim of this study was to quantify the energy cost and the cardiorespiratory
      response while walking at free speed with an Advanced Reciprocating Gait Orthosis
      (ARGO). The study was conducted on a group of six male paraplegic patients, age
      range 16-31 years (median = 22.50), with complete traumatic injuries ranging from
      T3 to T12 and a median time lapse from the trauma of 21 months. The data was
      recorded 6-8 weeks after the patients were fitted and trained to use the
      orthosis. Maintaining a standing position produced a significant increase of both
      the heart rate (HR) and the respiratory rate (RR), whilst the increase of energy
      consumption was not significant. The data for median speed, energy consumption
      and energy cost observed during free walking was similar to that of the
      Reciprocating Gait Orthosis (RGO) in thoracic level paraplegic individuals. This
      study indicates that in the utilisation of the ARGO the workload is not excessive
      when it is limited to maintaining a standing position. In contrast, walking
      results in early anaerobic conditions and unsustainable fatigue after short
      distances. The great energy cost recorded is considered to be a main reason for
      the frequent abandonment or the low utilisation of the orthosis at follow-up.

PMID- 9589521
TI  - Glucose intolerance and dyslipidaemias in persons with paraplegia and tetraplegia
      in south India.
AB  - Glucose intolerance and dyslipidaemias have been reported among paraplegics and
      tetraplegics. In this study we determined the lipid profiles and the glucose
      tolerance in a group of 48 persons with spinal cord lesions who had been
      rehabilitated in our Department of Physical Medicine and Rehabilitation. This non
      randomised, descriptive study was conducted as part of the annual medical follow
      up of these individuals. Hypertension was observed in only 6% of the subjects.
      Fasting hyperglycemia was observed in 19% and glucose intolerance in 23% of the
      subjects. Total cholesterol was abnormal in 2%, but 58% had low levels of high
      density lipoprotein (HDL). 10% of the subjects had raised low density lipoprotein
      (LDL) levels. The cardioprotective HDL fraction may remain very low even while
      the total cholesterol level is within normal limits, and unless a lipid profile
      estimation is done, this group of individuals who are at cardiovascular risk may
      remain undetected. We conclude that glucose intolerance and dyslipidaemias are
      common among paraplegic and tetraplegic individuals, and these metabolic
      derangements may contribute to increased cardiovascular morbidity.

PMID- 9589523
TI  - Effect of aerobic training on ventilatory muscle endurance of spinal cord injured
      men.
AB  - The functional consequences of ventilatory muscle impairment of spinal cord
      injured (SCI) subjects has been evaluated through spirometric and maximal
      respiratory pressure tests. Nevertheless, underlying functional abnormalities may
      be evident only under dynamic conditions, such as with a ventilatory muscle
      endurance test (VME). In order to evaluate the VME of thoracic SCI men and the
      effect of physical training on it we evaluated 12 SCI subjects (Group I) and 12
      able-bodied controls (Group II). The subjects were submitted to clinical
      evaluation, spirometry, maximum voluntary ventilation in 12 s (MVV-12 sec) and a
      test of VME-the highest time of sustained ventilation at 70% of the maximum
      voluntary ventilation in isocapnic conditions (MVV-70% time). Gr. II was
      evaluated before and after an arm cranking aerobic training program (30
      min/session, three times/week, 6 weeks) with training target heart rate
      corresponding to ventilatory anaerobic threshold. On the initial evaluation, Gr.
      I subjects presented a significantly reduced forced vital capacity (FVC), forced
      expiratory volume in 1 s (FEV1) and MVV-12 sec when compared to controls (P <
      0.05). Also, the VME was severely reduced in Group I (median, ranges; 1.15, 0.61
      12.22) when compared to Group II (14.60, 1.20-15.00) - P < 0.001. When Gr. I
      subjects were separated by the level of lesion, the VME was lower in high injured
      (T1-T7) than intermediate (T8-T10) and low injured patients (T11-T12)-P < 0.05.
      After aerobic training, Group I subjects incremented significantly the FVC (P <
      0.05) and the VME (P < 0.001), so that MVV-70% time values post-training were not
      different from the initial values of the Gr. II. In conclusion, (i) the VME of
      thoracic SCI men was severely reduced when compared to able-bodied controls; (ii)
      a 6-weeks arm cranking aerobic training program was efficient to normalize the
      VME of SCI subjects.

PMID- 9589522
TI  - Sleep apnoea related hypoxia is associated with cognitive disturbances in
      patients with tetraplegia.
AB  - Sleep disordered breathing is common in patients with tetraplegia. Nocturnal
      arterial hypoxemia and sleep fragmentation due to sleep apnoea may be associated
      with cognitive dysfunction. We therefore studied the influence of sleep
      disordered breathing on neuropsychological function in 37 representative
      tetraplegic patients (mean age 34 +/- 9.7 years). Thirty percent (11 of 37
      patients) had clinically significant sleep disordered breathing, defined as
      apnoea plus hypopnoea index (AHI) greater than 15 per hour of sleep. Most apnoeas
      were obstructive in type. Seven patients (19%) desaturated to < 80% during the
      night. Neuropsychological variables were significantly correlated with measures
      of sleep hypoxia, but not with the AHI and the frequency of sleep arousals. The
      neuropsychological functions most affected by nocturnal desaturation were: verbal
      attention and concentration, immediate and short-term memory, cognitive
      flexibility, internal scanning and working memory. There appeared to be a weak
      association between the presence of severe sleep hypoxia and visual perception,
      attention and concentration but no association was found between sleep variables
      and depression scores. We concluded that sleep disordered breathing is common in
      patients with tetraplegia and may be accompanied with significant oxygen
      desaturation. The latter impairs daytime cognitive function in these patients,
      particularly attention, concentration, memory and learning skills. Cognitive
      disturbances resulting from sleep apnoea might adversely affect rehabilitation in
      patients with tetraplegia.

PMID- 9589524
TI  - Continent ileocecal augmentation cystoplasty.
AB  - OBJECTIVES: To evaluate the use of the ileocecal bowel segment for bladder
      augmentation in a select group of patients who need a low pressure, high capacity
      urinary storage mechanism and a continent, catheterisable, cutaneous stoma that,
      because of their physical limitations, is easier to catheterize than their native
      urethra. METHODS: We reviewed records of 23 continent ileocecal augmentation
      cystoplasties performed over the last 5 1/2 years. The goals of the operation,
      patient selection criteria, pre-operative evaluation, operative technique, and
      post-operative evaluation with results were studied. RESULTS: Twenty-three
      patients underwent the procedure with the average follow-up being 26.9 months
      (range 3-67 months). Bladder capacity was increased by an average of 276.8
      milliliters (ml). No metabolic problems have been detected, and 95% (22/23
      patients) are continent via their urethra and stoma. CONCLUSIONS: This unique
      modification of the Indiana continent urinary reservoir is not technically
      difficult to create and is relatively free of complications. The bladder capacity
      is greatly increased and post-operative continence rates are excellent. Finally,
      the quality of life for these patients has been significantly improved by their
      ability to access the augmented bladder independently via an abdominal stoma.

PMID- 9589525
TI  - Partner relationships, functioning, mood and global quality of life in persons
      with spinal cord injury and traumatic brain injury.
AB  - The aim of this study was to assess and compare spinal cord injured (SCI) and
      traumatic brain injured (TBI) persons and people from the general population
      concerning partner relationships, functioning, mood and global quality of life.
      One hundred and sixty seven SCI persons, 92 TBI persons and 264 controls
      participated in the study. The median age was: SCI persons 33 years (range 19 to
      79 years), TBI persons 40 years (range 20 to 70 years), and controls 31 years
      (range 19 to 79 years). Age at injury ranged among SCI persons from 14 to 76
      years (Md 28 years), and among TBI persons from 16 to 56 years (Md 32 years).
      Half of the SCI group (51%), 58% of the TBI group and 59% of the controls had a
      stable partner relationship at the time of the investigation. Many of these SCI
      and TBI relationships (38% and 55% respectively) were established after injury.
      Both SCI and TBI persons showed significantly more depressive feelings compared
      with the controls. Perceived quality of life (global QL rating) was significantly
      lower in the SCI group compared with the controls, whereas the ratings of TBI
      persons and controls did not differ significantly. SCI and TBI persons did not
      differ significantly in level of education, perceived quality of life or
      distress. In all three groups, global quality-of-life ratings were significantly
      lower among single persons compared to those with a partner relationship. It was
      concluded that both SCI and TBI appear to affect overall quality of life and
      mental well-being negatively. The number of partner relationships contracted
      after injury among both SCI and TBI persons indicates, however, that the injury
      is not a major barrier to establishing close partner relationships. Being in good
      spirits, that is, lack of depressive feelings has a profound impact on the
      perception of a high quality of life in all three groups. For the SCI and TBI
      persons, a high level of physical and social independence were further positive
      determinants of a perceived high quality of life.

PMID- 9589526
TI  - Spinal injury rehabilitation complicated by psycho-social problems.

PMID- 9589527
TI  - Long-term survival in spinal cord injury: a fifty year investigation.
AB  - The aims of this study were to examine long-term survival in a population-based
      sample of spinal cord injury (SCI) survivors in Great Britain, identify risk
      factors contributing to deaths and explore trends in cause of death over the
      decades following SCI. Current survival status was successfully identified in
      92.3% of the study sample. Standardised mortality ratios (SMRs) were calculated
      and compared with a similar USA study. Relative risk ratio analysis showed that
      higher mortality risk was associated with higher neurologic level and
      completeness of spinal cord injury, older age at injury and earlier year of
      injury. For the entire fifty year time period, the leading cause of death was
      related to the respiratory system; urinary deaths ranked second followed by heart
      disease related deaths, but patterns in causes of death changed over time. In the
      early decades of injury, urinary deaths ranked first, heart disease deaths second
      and respiratory deaths third. In the last two decades of injury, respiratory
      deaths ranked first, heart related deaths were second, injury related deaths
      ranked third and urinary deaths fourth. This study also raises the question of
      examining alternative neurological groupings for future mortality risk analysis.

PMID- 9589528
TI  - Evaluating neurological group homogeneity in assessing the mortality risk for
      people with spinal cord injuries.
AB  - A study of 3178 individuals injured in Britain between 1943 and 1990 and
      surviving the first year post-injury was conducted to evaluate the homogeneity of
      mortality risk ratios within groups based on varying degrees of neurological
      injury level and completeness of the injury. The study shows that it is less than
      optimal to combine individuals into neurological groupings of C1-C4 ABC, C5-C8
      ABC and T1-S5 ABC since the risk ratios are not homogeneous within these groups.
      Similarly, combining individuals into neurological groupings of tetraplegia
      complete, tetraplegia incomplete, paraplegia complete and paraplegia incomplete
      may not be appropriate for the same reasons. The consequence of performing a
      survival analysis using either of the traditional sets of groups is to dilute the
      risk ratios for a subset of individuals within a particular group, thereby
      providing less discrimination between neurological groups. Cox proportional
      hazards regression was employed to determine a set of neurological groupings with
      homogeneous risk ratios within a group while providing better differentiation
      between groups.

PMID- 9589530
TI  - Spinal extradural cysticercosis: a case report.
AB  - An extremely rare case of extradural spinal cysticercosis in an adult male is
      presented. The patient had evidence of extradural granulation tissue with
      associated destruction of C4 and C5 pedicles and laminae, causing tetraparesis.
      Histopathological examination revealed evidence of a degenerated cysticercal cyst
      with host tissue reaction. The patient made a gradual and marked improvement
      after decompression. Though rare, cysticercosis as a possible etiology of
      extradural spinal compression may be considered in endemic area.

PMID- 9589529
TI  - The Norwegian Polio Study 1994: a nation-wide survey of problems in long-standing
      poliomyelitis.
AB  - 'The Norwegian Polio Study 1994' was performed to make a nation-wide survey of
      the medical and social situation, and of the needs of anterior poliomyelitis
      (polio). A questionnaire, consisting of 133 questions with sub-questions, was
      sent to a total of 2392 polio victims, most of them registered in 'The National
      Society of Polio Victims' in Norway. 1449 persons (61%) answered. Sixty-six per
      cent were between 45 and 64 years of age, 25% were above 64 years and 9% were
      under 45 years. When specifying new health problems, 85% stated that they had
      experienced increased weakness in muscles affected by polio, while 58% had
      experienced increased weakness in previous non-affected muscles. Other health
      problems related to polio were fatigue during exercise (80%), general fatigue
      (57%), joint pain (58%), muscular pain (58%) and cold intolerance (62%). The
      participants indicated an increasing need of aids, but 80% were still independent
      of help from others and 57% were still employed, fully or part time. Only 17%
      were satisfied with the public health services for polio survivors, while 67% of
      those who had undergone comprehensive examination at some central hospital were
      satisfied. This study indicates an obvious need of building up expertise in
      multidisciplinary evaluation and treatment of post polio problems in countries
      where acute polio has been eliminated.

PMID- 9589531
TI  - Spinal cord injury secondary to cervical disc herniation in ambulatory patients
      with cerebral palsy.
AB  - Early onset of degeneration of the cervical spine and instability due to
      sustained abnormal tonicity or abnormal movement of the neck are found in
      patients with cerebral palsy. An unexplained change or deterioration of
      neurological function in patients with cerebral palsy should merit the
      consideration of the possibility of cervical myelopathy due to early degeneration
      or instability of the cervical spine. We describe two patients who had a spinal
      cord injury due to a cervical disc herniation, one patient was athetoid and the
      second had spastic diplegia, they both had cerebral palsy. It is not easy to
      determine whether new neurological symptoms are as a result of the cervical
      spinal cord disorder. These cases suggest that consideration of a cervical spine
      disorder with myelopathy is required in the evaluation of patients with cerebral
      palsy who develop deterioration of neurological function or activities over a
      short period of time.

PMID- 9589532
TI  - Pressure ulcer and amyloidosis.

PMID- 9589533
TI  - The internal bony architecture of the sacrum.
AB  - STUDY DESIGN: Radiographic and direct quantitative measurements were made of the
      cortical and the trabecular anatomy of the sacrum. OBJECTIVES: To define the
      trabecular patterns and the cortical thickness of the sacrum. SUMMARY OF
      BACKGROUND DATA: The sacrum is a frequent site of internal fixation. In previous
      anatomic studies, investigators have focused on specific dimensional measurements
      of the sacrum, whereas others have described the anatomic course of the anterior
      sacral neurovascular or visceral structures. Computed tomographic imaging also
      has been used to quantify the sacral trabecular bone density. The internal
      architecture of the sacrum has yet to be described in detail. METHODS: Seventeen
      cadaveric sacra were studied by computed tomographic imaging and then were
      sectioned at 3-mm intervals in the axial or sagittal plane. The cortical
      thickness of each section was measured under microscopic visualization. The
      sections were radiographed with high-resolution imaging to delineate their
      trabecular patterns. RESULTS: The trabecular bone was densest adjacent to the
      endplates. The sacral body trabeculae were arranged in a cruciate pattern, and
      bony atrophy occurred in a systematic fashion. An alar void was a consistent
      finding in all specimens with definable boundaries. The cortical thickness was
      uniform throughout the surface of each specimen. The computed tomographic images
      correlated with the anatomy observed in the cadaveric sections. CONCLUSION: The
      internal bony architecture of the sacrum has several consistent features. The
      relatively uniform cortical thickness seen in each sacral specimen may have
      clinical significance in the internal fixation of this region.

PMID- 9589534
TI  - Variation in surgical opinion regarding management of selected cervical spine
      injuries. A preliminary study.
AB  - STUDY DESIGN: The opinions of orthopedic surgeons and neurosurgeons were compared
      regarding appropriate management of selected cervical injuries and the timing of
      stabilization. OBJECTIVE: To determine whether there is consistency of opinion
      regarding the management of cervical trauma. SUMMARY OF BACKGROUND DATA: Numerous
      forms of management for cervical trauma exist, but there are few consistent
      recommendations. No previous study has been done to determine uniformity of
      preferences of the surgeons who manage these injuries. METHODS: Thirty-one
      orthopedic surgeons and neurosurgeons were given a brief clinical situation and
      pertinent radiographic studies of five selected cervical injuries. Management
      options included halo and nonhalo orthoses, traction, and various forms of
      anterior and/or posterior procedures. The surgeons rated, in whole numbers from 1
      to 10, their opinions on the appropriateness of each technique. Each surgeon was
      given a case of a "generic" cervical injury, in which stabilization was required
      and for which preoperative alignment was adequate in traction. They gave opinions
      on the timing of stabilization, with a choice of four time frames. Four
      neurologic situations were rated, ranging from intact to complete cord injury.
      RESULTS: Of 46 possible responses to the five test cases regarding
      appropriateness, 18 ranged from 1 to 10, the largest possible variation. Only 2
      had a range of 5 or less, implying better consensus among tested surgeons. Mean
      values ranged from 1.9 to 9.5. Agreementamong respondents regarding
      appropriateness was slight with a range of kappa statistics from 0.09 to 0.14. Of
      16 possible responses regarding timing, 14 were within a range of 8 or higher.
      Within 24 to 72 hours was the generally preferred time frame, with all possible
      responses showing a range of 3 or 4. Results of a multiple analysis of variance
      showed no significant differences among respondents. CONCLUSION: There is a large
      variety of opinion regarding appropriateness of specific operative and
      nonoperative management procedures and surgical timing among the surgeons polled
      who manage cervical trauma. This implies that there is no widely accepted
      standard management procedure for many of these injuries.

PMID- 9589535
TI  - High-dose methylprednisolone prevents extensive sick leave after whiplash injury.
      A prospective, randomized, double-blind study.
AB  - STUDY DESIGN: A prospective, randomized, double-blind study comparing high-dose
      methylprednisolone with placebo. OBJECTIVES: To evaluate the efficacy of high
      dose methylprednisolone when administered within 8 hours after whiplash injury.
      SUMMARY OF BACKGROUND DATA: Whiplash injury often results in chronic symptoms.
      The management of whiplash injuries is controversial, and pharmacologic therapy
      has received little evaluation. In recent reports, dysfunction of the central
      nervous system has been indicated in several cases. Methylprednisolone
      administered within 8 hours after the injury to patients with acute spinal cord
      injury has been demonstrated to improve the outcome. This procedure was also
      adopted in a randomized study of cases of whiplash injury in car accidents.
      METHODS: Forty patients, 22 men and 18 women with a mean age of 35 years (range,
      19-65), were included in the study, 20 in each of two groups. They were treated
      for whiplash injury, which they had sustained in car accidents. The patients were
      enrolled if their diagnoses were complete and treatment had begun within 8 hours
      after injury. Disabling symptoms severe enough to prevent the patient from
      returning to work, number of sick days before and after injury, and sick-leave
      profile after injury were used as parameters for the evaluation of the effects of
      the treatment. Baseline demographic data were controlled for when statistical
      analysis had been performed. RESULTS: At the follow-up examination 6 months after
      initial treatment, there was a significant difference in disabling symptoms
      between the actively treated patients and the placebo group (P = 0.047), total
      number of sick days (P = 0.01), and sick-leave profile (P = 0.003). CONCLUSIONS:
      The results of this study indicate that acute treatment with high-dose
      methylprednisolone may be beneficial in preventing extensive sick leave after
      whiplash injury. However, the number of patients studied was small, and therefore
      further prospective, controlled studies are needed.

PMID- 9589536
TI  - Regression of cervical disc herniation observed on magnetic resonance images.
AB  - STUDY DESIGN: A retrospective study of cervical disc herniation using results of
      repeated magnetic resonance imaging examinations. OBJECTIVES: To clarify the
      cervical disc herniation morphological changes over time in order to establish a
      strategy for treatment. SUMMARY OF BACKGROUND DATA: In the authors' previous
      magnetic resonance imaging follow-up study of patients with lumbar disc
      herniation, spontaneous regression was observed in the sequestration-type
      lesions, and it was found that the tendency toward regression differed based on
      the anatomic position of extruded disc material. METHODS: Thirty-eight patients
      with cervical disc herniation who underwent repeated magnetic resonance imaging
      examinations were studied. The changes over time in herniated disc size were
      evaluated using this imaging technique. Evaluation showed the characteristics of
      those in whom spontaneous regression was found, such as extrusion pattern, and
      the clinical outcome was evaluated by symptoms. RESULTS: In 15 patients (40%),
      the volume of herniated material was decreased. The interval from onset of
      symptoms to the initial examination was significantly shorter in the regression
      group than in the group that showed no change in disc herniation. By extrusion
      pattern, cervical disc herniation, which was divided into migration type on
      sagittal view and lateral type on axial view, most frequently exhibited
      spontaneous regression. All of the patients with radicular pain and upper limb
      amyotrophy were treated successfully with conservative therapy. CONCLUSION:
      Although the possibility of the combination of hemorrhage and disc material could
      not be denied, active resorption of herniated material probably occurred during
      the acute phase. Extruded material exposed to the epidural space may be resorbed
      more quickly than that beneath the ligament. Vascular supply probably plays a
      role in the mechanism of resorption. The phase and position of extrusion were the
      significant factors affecting cervical disc herniation resorption. It was
      demonstrated that examination performed during the acute phase using magnetic
      resonance imaging is necessary for elucidation of the pathogenesis of cervical
      disc herniation, and that migrating, lateral-type herniations regress so
      frequently that conservative treatment should be chosen not only for patients
      with radicular pain, but also for those with upper limb amyotrophy.

PMID- 9589537
TI  - Congenital scoliosis caused by a unilateral failure of vertebral segmentation
      with contralateral hemivertebrae.
AB  - STUDY DESIGN: The medical records and serial spine radiographs of 59 consecutive
      patients with congenital scoliosis caused by unilateral unsegmented bar with
      contralateral hemivertebrae were reviewed. OBJECTIVES: To study the presentation,
      natural history, and treatment of these patients. SUMMARY AND BACKGROUND DATA:
      This is the least common type of congenital scoliosis. METHODS: The mean age at
      diagnosis was 4 years 1 month. Forty-three patients were observed without
      treatment for a mean of 6 years and 1 month. Prophylactic arthrodesis was
      performed in 10 patients before they were 5 years old. Thirty-five patients had a
      corrective procedure and arthrodesis after they were 5 years old. RESULTS:
      Thoracolumbar curves had the worst prognosis. Without management all but two
      exceeded 50 degrees when the patients were 2 years old. All untreated curves
      exceeded 88 degrees. Midthoracic curves had only a slightly less severe
      prognosis, and all but one exceeded 40 degrees by the time the patient was 2
      years old. All untreated curves exceeded 70 degrees. In eight of the 14 patients
      whose congenital curves had their apexes at T5, T6, or T7, a long secondary
      structural curve developed on the opposite side in the thoracolumbar region, and
      this contributed significantly to the overall deformity. Occult intraspinal
      anomalies were present in 24 patients (41%). Surgical treatment after the patient
      was 5 years old was not successful in producing significant correction of these
      severe rigid deformities. CONCLUSION: These patients have the most rapidly
      progressive and severely deforming of all types of congenital scoliosis. All
      midthoracic, thoracolumbar, and lumbar curves require immediate prophylactic
      surgical treatment by anterior and posterior arthrodesis--preferably in the first
      year of life.

PMID- 9589538
TI  - Surgical correction of scoliosis in patients with generalized seizures. Risk of
      vertebral body fracture.
AB  - STUDY DESIGN: A retrospective evaluation of the outcome of surgical management of
      progressive scoliosis in institutionalized patients with frequent, uncontrolled,
      generalized tonic clonic seizures. OBJECTIVES: To determine the safety and
      stability of internal fixation devices in patients with progressive scoliosis and
      intractable seizures. SUMMARY OF BACKGROUND DATA: Progressive scoliosis is a
      common problem in severely disabled patients. It has been the belief among some
      spine physicians that the coexistence of intractable seizures with progressive
      scoliosis is a contraindication for surgery, because most of the thoracic and
      lumbar spine is fixed and "unyielding" after internal fixations, increasing the
      risk of vertebral fractures. There have been reports of fracture of fixation
      devices, particularly Harrington rods, under conditions of massive trauma or
      mechanical stress, such as seizures. METHODS: The authors reviewed the outcome of
      six profoundly retarded institutionalized patients with a history of intractable
      seizures who underwent internal fixation of the spine between 1984 and 1987
      because of progressive scoliosis. Seizure types and frequency of convulsion were
      obtained from the institutional charts. Follow-up radiographs of the spine
      obtained at 1, 3, and 6 months after the surgery and once a year thereafter were
      reviewed by the radiologist and orthopedic surgeon with special attention paid to
      fractures, stability of the fusion, and integrity of the instrumentation.
      RESULTS: Six patients underwent spinal fusion with internal spinal fixation, four
      patients with Harrington rods and two with Luque rods. All patients had
      refractory tonic clonic seizures ranging from 11 to 80 generalized tonic clonic
      convulsions per year for the 10-year follow-up period after surgery. There were
      no fractures, subluxation, or pseudoarthrosis of the fused vertebrae or the
      vertebral bodies adjacent to the fusion. There were no fractures of the
      instrumentation. CONCLUSIONS: The authors' findings suggest that when appropriate
      fusion is attained, the use of internal fixation devices is not contraindicated
      in the management of progressive scoliosis in patients with intractable seizures.

PMID- 9589539
TI  - Unilateral hip rotation range of motion asymmetry in patients with sacroiliac
      joint regional pain.
AB  - STUDY DESIGN: A cross-sectional study was used to determine whether limited range
      of motion in the hip was present in 100 patients--one group with unspecified low
      back pain and another group with signs suggesting sacroiliac joint dysfunction.
      OBJECTIVES: To determine whether a characteristic pattern of range of motion in
      the hip is related to low back pain in patients and to determine whether such a
      pattern is associated with and without signs of sacroiliac joint dysfunction.
      SUMMARY OF BACKGROUND DATA: The sacroiliac joint is often considered a potential
      site of low back pain. Problems with the sacroiliac joint, as well as with the
      low back, have often been related to reduced or asymmetric range of motion in the
      hip. The correlation between sacroiliac joint dysfunction and hip range of
      motion, however, has not been thoroughly evaluated with reliable tests in a
      population of patients with low back pain. METHODS: Passive hip internal and
      external rotation goniometric measurements were taken by a blinded examiner,
      while a separate examiner evaluated the patient for signs of sacroiliac joint
      dysfunction. Patients with sacroiliac joint dysfunction were further classified
      as having a left or a right posteriorly tilted innominate. RESULTS: The patients
      with low back pain but without evidence of sacroiliac joint dysfunction had
      significantly greater external hip rotation than internal rotation bilaterally,
      whereas those with evidence of sacroiliac joint dysfunction had significantly
      more external hip rotation than internal rotation unilaterally, specifically on
      the side of the posterior innominate. CONCLUSIONS: Clinicians should consider
      evaluating for unilateral asymmetry in range of motion in the hip in patients
      with low back pain. The presence of such asymmetry in patients with low back pain
      may help identify those with sacroiliac joint dysfunction.

PMID- 9589541
TI  - Sick leave and disability pension among passenger car occupants injured in urban
      traffic.
AB  - STUDY DESIGN: A follow-up cohort study of passenger car occupants injured in car
      crashes in an urban area in Sweden. OBJECTIVES: To analyze the injuries, injury
      events, and long-term consequences of injuries in car crashes. SUMMARY OF
      BACKGROUND DATA: The consequences of car crashes usually are described in terms
      of the number of people injured, the severity of injuries, or the number of
      inpatient days. Certain types of crash injuries can results in long-term sick
      leave and granting of disability pension. The increased socioeconomic
      significance of these outcomes is not always indicated by analysis of commonly
      used variables. METHODS: Two hundred fifty-five passenger car occupants aged 16
      64 years who were injured in car crashes in urban traffic were analyzed in terms
      of length of sick leave and receipt of disability pension. RESULTS: Strain of the
      cervical spine was the most common type of injury (55%, 141 injuries), and these
      injuries accounted for 82% of all sick leave taken within 2.5 years after the
      injury event. Injury to the cervical spine in 16 of 18 cases resulted in long
      term sick leave or dependence on disability pension. The most common injury
      mechanism was rear-end collisions (39%). This type of crash resulted in 64% of
      all sick-leave days within 2.5 years after the injury event. Twelve out of 18
      injured people on long-term sick leave or receiving disability pension had been
      in cars struck from behind. CONCLUSIONS: It is important to include long-term
      consequences in the form of sick leave and disability pension when describing the
      consequences of different types of car crashes and injuries.

PMID- 9589540
TI  - Motor-evoked potentials from various levels of paravertebral muscles in normal
      subjects and in patients with focal lesions of the spinal cord.
AB  - STUDY DESIGN: This prospective study includes normal control subjects and
      patients with focal lesions of the spinal cord investigated by transcranial
      magnetic stimulation. OBJECTIVES: To establish a stable method to elicit motor
      evoked potentials from cervical to lumbar segmental levels and to apply the
      method that would allow the localization in patients with restricted cord lesion.
      Thirty-four healthy subjects (10 women, 24 men) and 17 patients with focal spinal
      lesions were admitted to this study. SUMMARY OF BACKGROUND DATA: The focal cord
      lesions and injuries were previously evaluated by the records of lower limb
      muscles after cortical stimulation, but this method did not demonstrate the
      vertebral levels at which the lesions were located. METHODS: The paravertebral
      myotomal-evoked potentials were recorded in different segmental levels (T1, T6,
      T12, and L3) from paravertebral muscles, using surface and needle electrodes by
      transcranial magnetic stimulation in normal control subjects and patients.
      RESULTS: In normal control subjects, paravertebral myotomal-evoked potentials
      were obtained from T1, T6, T12, and L3 paravertebral muscles with both recording
      techniques (surface and needle electrode). From T1 to L3 latencies of
      paravertebral myotomal-evoked potentials increased gradually (from 10 msec to 17
      msec) in normal control subjects. The levels of spinal cord lesions were obtained
      reliably in 14 of 17 patients with thoracic-lumbar spinal cord lesions, by using
      both electrophysiologic methods. In 11 of 14 patients, the lesions produced total
      conduction block, at and below the lesion level. In the remaining 3 patients
      slowing of intersegmental conduction was observed along the focal cord lesion.
      CONCLUSIONS: The paravertebral myotomal-evoked potentials obtained by surface
      electrode from paravertebral muscles and by midline needle electrode in the
      intrinsic rotatory muscles of the spine were useful in localizing lesions in the
      spinal segments in most of the patients with thoracic-lumbar cord lesions.

PMID- 9589542
TI  - Familial predisposition for lumbar degenerative disc disease. A case-control
      study.
AB  - STUDY DESIGN: A case-control study using magnetic resonance imaging and plain
      radiography to evaluate whether a family history of lumbar disc herniation is a
      risk factor for disc degeneration. OBJECTIVES: To evaluate the significance of a
      family history of operated lumbar disc herniation in the development of lumbar
      disc degeneration and lumbar disc herniation. SUMMARY OF BACKGROUND DATA: There
      are only a few epidemiologic studies indicating that a family history of
      intervertebral disc herniation is a risk factor for juvenile disc herniation.
      Recently, similarities in degenerative findings of the lumbar spine between
      identical twins have been reported. METHODS: In the case group, 24 patients who
      were the immediate relatives of patients who had undergone surgery for disc
      herniation and who presented or had a history of low back pain and/or unilateral
      leg pain were included. Control individuals included 72 age- and gender-matched
      outpatients who reported low back pain and/or leg pain without a family history
      of operated disc herniation. The incidence, level, and topographic location of
      disc herniation/diffuse bulge; the incidence and grade of disc degeneration
      observed on magnetic resonance images; and degenerative changes suggesting disc
      degeneration observed on plain radiographs were compared between the relatives of
      patients with disc herniation (cases) and the controls. RESULTS: The incidence of
      disc degeneration at L4-L5 and L5-S1 in cases (L4-L5, 18/24; L5-S1, 18/24) and
      controls (L4-L5, 45/72; L5-S1, 43/72) was similarly high. However, the grade of
      disc degeneration according to magnetic resonance imaging signal intensity on the
      T2-weighted sagittal image using Schneiderman's four-grade classification was
      significantly more severe in cases (L4-L5: Grade 1, 6/24; Grade 2, 4/24; Grade 3,
      13/ 24; Grade 4, 1/24; L5-S1: Grade 1, 6/24; Grade 2: 3/24, Grade 3: 12/24, Grade
      4: 3/24) than in controls (L4-L5: Grade 1, 27/72; Grade 2, 24/72; Grade 3, 20/72;
      Grade 4, 1/72; P = 0.034; L5-S1: Grade 1, 29/72; Grade 2, 23/72; Grade 3, 13/72;
      Grade 4, 7/72; P = 0.023; Mann-Whitney U test). The incidence of disc
      herniation/diffuse bulge at L4-L5 (16/24) and L5-S1 (11/24) in cases was higher
      than that in controls (L4-L5, 33/72; P = 0.07; L5-S1, 17/ 72; P = 0.04; chi
      square test). CONCLUSION: The current study provided evidence that a family
      history of operated lumbar disc herniation has a significant implication in
      lumbar degenerative disc disease. There may be a genetic factor in the
      development of lumbar disc herniation as an expression of disc degeneration.

PMID- 9589543
TI  - The role of complex, simultaneous trunk motions in the risk of occupation-related
      low back disorders.
AB  - STUDY DESIGN: Simultaneous trunk kinematic variables of industrial workers
      performing jobs with varying degrees of low back disorder risk were quantified,
      by using a three-dimensional electrogoniometer. OBJECTIVES: To assess the
      distinguishing patterns of simultaneous multidimensional (complex) motion
      parameters of workers performing manual material handling jobs with varying
      degrees of low back disorder risk. SUMMARY OF BACKGROUND DATA: There is
      significant epidemiologic and biomechanical evidence that implicates
      simultaneously occurring or combined motions and loading as important risk
      factors follow back disorder. However, the specific levels or magnitudes and
      patterns of these complex motions at which risk of low back disorder is increased
      are still unknown. METHODS: An industrial database of 126 workers and jobs was
      used to quantify the complex trunk motions of groups with varying degrees of low
      back disorder risk. Three groups, low-, medium-, and high-risk, were defined on
      the basis of retrospective injury records of the corresponding jobs. The jobs
      were further classified into five cells of weight-lift rate combinations. Within
      each weight-lift rate cell, the three-dimensional trunk motion patterns of
      workers were analyzed. Bivariate distributions and cumulative distribution
      functions were used to compare the simultaneous occurrence of complex dynamic
      motions among risk groups. RESULTS: High- and medium-risk groups exhibited
      complex trunk motion patterns involving high magnitudes of combined velocities,
      especially at extreme sagittal flexion; whereas the low-risk group did not.
      Postural trunk information alone did not provide a consistent pattern of
      distinguishing among risk groups. CONCLUSIONS: Elevated levels of complex
      simultaneous velocity patterns were unique to groups with increased low back
      disorder risk. Knowledge of these complex trunk velocity patterns in combination
      with key workplace factors provides a more sensitive means for identifying low
      back disorder occupational risk factors than does mere postural information.

PMID- 9589544
TI  - "Whiplash associated disorders: redefining whiplash and its management" by the
      Quebec Task Force. A critical evaluation.
AB  - STUDY DESIGN: The two publications of the Quebec Task Force on Whiplash
      Associated Disorders were evaluated by the authors of this report for
      methodologic error and bias. OBJECTIVES: To determine whether the conclusions and
      recommendations of the Quebec Task Force on Whiplash-Associated Disorders
      regarding the natural history and epidemiology of whiplash injuries are valid.
      SUMMARY OF THE BACKGROUND DATA: In 1995, the Quebec Task Force authored a text
      (published by the Societe de l'Assurance Automobile du Quebec) and a pullout
      supplement in Spine entitled "Whiplash-Associated Disorders: Redefining Whiplash
      and its Management." The Quebec Task Force concluded that whiplash injuries
      result in "temporary discomfort," are "usually self-limited," and have a
      "favorable prognosis," and that the "pain [resulting from whiplash injuries] is
      not harmful." METHODS: The authors of the current report reviewed the text and
      the supplement for methodologic flaws that may have threatened the validity of
      the conclusions and recommendations of the Quebec Task Force. RESULTS: Five
      distinct and significant categories of methodologic error were found. They were:
      selection bias, information bias, confusing and unconventional use of
      terminology, unsupported conclusions and recommendations, and inappropriate
      generalizations from the Quebec Cohort Study. CONCLUSION: The validity of the
      conclusions and recommendations of the Quebec Task Force regarding the natural
      course and epidemiology of whiplash injuries is questionable. This lack of
      validity stems from the presence of bias, the use of unconventional terminology,
      and conclusions that are not concurrent with the literature the Task Force
      accepted for review. Although the Task Force set out to redefine whiplash and its
      management, striving for the desirable goal of clarification of the numerous
      contentious issues surrounding the injury, its publications instead have confused
      the subject further.

PMID- 9589545
TI  - Morphogenesis of vertebral deformities in involutional osteoporosis. Age-related,
      three-dimensional trabecular structure.
AB  - STUDY DESIGN: The relation between the semiquantitative data of alteration in
      three-dimensional trabecular structure and deformities of the vertebral body was
      analyzed to clarify the morphogenesis of vertebral deformities in involutional
      osteoporosis. OBJECTIVES: To evaluate semiquantitatively the age-related
      alterations of the three-dimensional structure of trabeculae of the vertebral
      body and to clarify their relation to vertebral deformities in involutional
      osteoporosis. SUMMARY OF BACKGROUND DATA: Recent studies have shown that bone
      fractures and deformities in osteoporosis do not depend only on a reduced amount
      of bone tissue. There is no previous study on the relation between bone deformity
      and the alterations of the three-dimensional structure of trabeculae. METHODS:
      The second lumbar vertebrae were removed at autopsy from 25 patients who had no
      disease predisposing them to secondary osteoporosis and no severe vertebral
      deformities. The sections of the vertebral body were immersed in sodium
      hypochlorite solution to corrode the bone marrow. Atrophy of trabeculae and
      increased spacing between trabeculae were evaluated semiquantitatively under
      stereoscopic microscopy. The authors examined the relation between the
      semiquantitative data found in the autopsy vertebrae and the patterns and
      frequencies of each deformity of the second lumbar vertebrae in 99 patients with
      involutional osteoporosis. RESULTS: The most frequent vertebral deformity was
      wedge-shaped vertebrae with compression of the anterosuperior portion, and the
      alterations of the trabecular structure of the anterosuperior portion were severe
      and closely related to aging. Severe trabecular alterations with no relation to
      aging did not necessarily cause vertebral deformity. CONCLUSIONS: Trabecular
      abnormality, which is significantly correlated with aging, may be the necessary
      and sufficient condition for vertebral deformities in involutional osteoporosis.

PMID- 9589546
TI  - Spontaneous remodeling of the spinal canal after conservative management of
      thoracolumbar burst fractures.
AB  - STUDY DESIGN: Forty-two conservatively treated patients with a burst fracture of
      the thoracic, thoracolumbar, or lumbar spine with more than 25% stenosis of the
      spinal canal were reviewed more than 1 year after injury to investigate
      spontaneous remodeling of the spinal canal. OBJECTIVES: To investigate the
      natural development of the changes in the spinal canal after thoracolumbar burst
      fractures. SUMMARY OF THE BACKGROUND DATA: Surgical removal of bony fragments
      from the spinal canal may restore the shape of the spinal canal after burst
      fractures. However, it was reported that restoration of the spinal canal does not
      affect the extent of neurologic recovery. METHODS: Using computerized tomography,
      the authors compared the least sagittal diameter of the spinal canal at the time
      of injury with the least sagittal diameter at the follow-up examination. RESULTS:
      Remodeling and reconstitution of the spinal canal takes place within the first 12
      months after injury. The mean percentage of the sagittal diameter of the spinal
      canal was 50% of the normal diameter (50% stenosis) at the time of the fracture
      and 75% of the normal diameter (25% stenosis) at the follow-up examination. The
      correlation was positive between the increase in the sagittal diameter of the
      spinal canal and the initial percentage stenosis. There was a negative
      correlation between the increase in the sagittal diameter of the spinal canal and
      age at time of injury. Remodeling of the spinal canal was not influenced by the
      presence of a neurologic deficit. CONCLUSION: Conservative management of
      thoracolumbar burst fractures is followed by a marked degree of spontaneous
      redevelopment of the deformed spinal canal. Therefore, this study provides a new
      argument in favor of the conservative management of thoracolumbar burst
      fractures.

PMID- 9589547
TI  - Distraction of lumbar vertebrae in gravitational traction.
AB  - STUDY DESIGN: Experimental study of 30 patients diagnosed with low back pain
      resulting from lumbar disc herniation, disc degeneration, and segmental
      instability. Patients underwent gravitational traction, and widening of the
      intervertebral space and posterior facets was measured on radiographs. This same
      procedure was performed with a group of 30 healthy individuals. OBJECTIVES: To
      determine the effect of gravitational traction on the widening of the
      intervertebral space and the other vertebral structures in patients with low back
      pain and in healthy individuals. SUMMARY OF BACKGROUND DATA: Gravitational
      traction is performed by suspending the patient in a hanging, upright position
      for an extended period of time. In spite of disagreement among authors about the
      effect of lumbar traction, recent innovations have enabled the distraction of
      vertebrae. METHODS: A specially designed apparatus was used to apply
      gravitational traction. Pre- and post-traction radiographs were obtained to study
      the changes in the L2-L3, L3-L4, L4-L5, and L5-S1 intervertebral spaces;
      Ferguson's angle; L1-S1 total distance; and blood pressure. RESULTS: Distraction
      was more than approximately 3 mm in each intervertebral space in both groups.
      CONCLUSION: Gravitational traction had a very apparent effect on intervertebral
      space and was found to be an effective method to distract lumbar vertebrae.
      Discomfort experienced by the patient during suspension may be overcome by making
      biomedical changes to the suspension corset.

PMID- 9589548
TI  - Anatomic considerations of pedicle screw placement in the thoracic spine. Roy
      Camille technique versus open-lamina technique.
AB  - STUDY DESIGN: In this cadaveric study, the outcomes of two techniques for pedicle
      screw placement in the thoracic spine were compared. OBJECTIVES: To assess the
      Roy-Camille technique, and to determine whether pedicle screw placement, aided by
      partial laminectomy, could decrease the incidence of pedicle violations. SUMMARY
      OF BACKGROUND DATA: Pedicle screw fixation in the thoracic spine remains
      technically challenging. The Roy-Camille method may be one of the leading
      techniques of thoracic pedicle screw placement. However, there are few studies
      evaluating this technique and determining methods to decrease the incidence of
      thoracic pedicle penetration with screw insertion. METHODS: Ten cadaveric
      thoracic spines from T1 to T10 were used for pedicle screw placement. Two
      techniques of transpedicular screw placement were used, the Roy-Camille technique
      (screw placed on the right side; used in 95 screw placements) and the open-lamina
      technique screw placement with combined partial laminectomy (screw placed on the
      left side; used in 94 screw placements). After screw placement, all specimens
      were evaluated visually to determine violation of the pedicle. RESULTS: The screw
      placement with the Roy-Camille technique had a higher percentage of pedicle
      violation (54.7%) than did that with the open-lamina technique (15.9%). No Grade
      III violation was seen in the screw placement with the open-lamina technique.
      CONCLUSIONS: The Roy-Camille technique was associated with a high incidence of
      pedicle violation, whereas screw placement with a partial laminectomy
      significantly reduced the incidence of pedicle violation. Pedicle screw fixation
      in the thoracic spine remains a technical challenge and should not be used
      routinely. Screw placement with the open-lamina technique is recommended if
      pedicle screw fixation is strongly indicated in the thoracic spine.

PMID- 9589550
TI  - Spine update. Patient preferences and the development of practice guidelines.
AB  - One shortcoming of clinical practice guidelines is that generic, one-for-all
      guideline recommendations do not account for differences among patients' views
      about the desirability (or undesirability) of specific health outcomes, such as
      low back pain. Because differences in patients' preferences may lead to
      differences in the preferred therapy, a clinical practice guideline that does not
      consider patients' preferences may provide recommendations that are not optimal.
      Recently developed methodologic approaches enable guideline developers to assess
      the role of patients' preferences in clinical decisions and guideline
      recommendations, and to develop preference-based guidelines. Preference-based
      guidelines are more likely to meet criteria for high-quality guidelines than are
      guidelines developed without consideration of the role of patients' preferences.
      Guideline developers should identify decisions in which patient preferences are
      important and note these decisions clearly in the written guideline; indicate the
      specific health states for which preferences are important; and, if possible,
      provide recommendations about options for preference assessment. These options
      range from informal discussions with patients to computer-based utility
      assessments. Patients' preferences are an important factor in clinical decisions
      regarding management of low-back pain, particularly in decisions about surgical
      management and symptom control. Although further research is needed to define the
      role of techniques for assessing patients' preferences in routine clinical
      practice, guideline developers can determine when patients' preferences should
      play a prominent role in guideline recommendations.

PMID- 9589549
TI  - Neuroaugmentation in the management of sacroiliac joint pain. Report of two
      cases.
AB  - STUDY DESIGN: A report of two cases of severe sacroiliac pain that were resistant
      to conventional management techniques. Both patients had undergone lumbar fusion.
      This appeared to be a predisposing factor. OBJECTIVE: To define the source of
      pain in these patients by performing a series of diagnostic blocks under
      fluoroscopic guidance to determine if these patients were candidates for
      neuroaugmentation. SUMMARY OF BACKGROUND DATA: Mild to moderate sacroiliac joint
      pain can be managed conservatively with analgesics, anti-inflammatory drugs, and
      physical therapy. Severe sacroiliac joint pain can be incapacitating and more
      challenging to manage. Fluoroscopically guided intra-articular local anesthetic
      steroid injections, followed by joint manipulation, can be effective,
      intracapsular injections of glycerin, glucose, and phenol also may be beneficial
      in some patients. The use of neuroaugmentation to manage pain of synovial origin
      has not been reported previously. Sacral nerve root stimulation in particular has
      been used to manage urinary bladder dysfunction and pain, but not sacroiliac
      joint pain. METHODS: Two patients with severe sacroiliac joint pain were treated
      by implanting a neuroprosthesis at the third sacral nerve roots. The patients had
      undergone lumbar fusion for back pain that developed as a result of work-related
      injuries. Stimulation was tried for 1 week with bilateral, percutaneously
      implanted, cardiac pacing wires at the third sacral nerve roots. RESULTS: Both
      patients experienced relief of approximately 60% of their pain during the trial
      period. Therefore, a neuroprosthesis (Medtronics, MN) was implanted permanently
      bilaterally at the third sacral nerve root in both patients. The use of
      analgesics was reportedly the same after implantation, but significantly more
      effective, and the patients' daily living activities were more tolerable.
      CONCLUSIONS: Two cases of refractory sacroiliac joint pain are reported that were
      managed with permanently implanted neuroprostheses at the third sacral nerve
      roots. The authors suggest that neuroaugmentation can be a reasonable option in
      selected patients with refractory sacroiliac pain.

PMID- 9589551
TI  - Synthesis of bile acid 24-acyl glucuronides.
AB  - The synthesis of acyl glucuronides of common bile acids is described. By means of
      the Mitsunobu reaction employing diethylazodicarboxylate and triphenylphosphine,
      bile acids were condensed through the inherent C-24 carboxy group with benzyl
      2,3,4-tri-O-benzyl-D-glucopyranuronate, which was prepared from 1-O-methyl-alpha
      D-glucose. The separation and purification of the beta-anomers at the anomeric
      position of the sugar moiety were attained by preparative thin-layer
      chromatography and/or high-performance liquid chromatography on a column packed
      with phenyl-bonded silica using H2O-MeOH as a mobile phase. The removal of the
      benzyl group on the sugar moiety was achieved by catalytic hydrogenation with 10%
      palladium on carbon to yield the desired acyl glucuronides of bile acids. The
      structures of these acyl glucuronides were confirmed by proton nuclear magnetic
      resonance spectral properties.

PMID- 9589552
TI  - Separation and characterization of carboxyl-linked glucuronides of bile acids in
      incubation mixture of rat liver microsomes.
AB  - The carboxyl-linked 24-glucuronides of common bile acids have been identified by
      means of liquid chromatography (LC)/atmospheric pressure chemical ionization
      (APCI)-mass spectrometry (MS) in an incubation mixture with a male Wistar rat
      liver microsomal fraction. The authentic specimens of bile acid 24-glucuronide
      acetate-methyl esters were synthesized unequivocally using the Mitsunobu
      reaction, and the APCI-mass spectrometric properties of these glucuronide
      derivatives were also characterized. After incubation of common unconjugated bile
      acids with hepatic microsomes, glucuronides were extracted and purified with a
      Sep-Pak C18 cartridge and lipophilic ion exchange gel, piperidino-hydroxypropyl
      Sephadex LH-20, and then derivatized into the acetate-methyl esters. Subsequent
      resolution into alpha- and beta-isomers at the glucuronosyl linkage was attained
      by LC on Cosmosil 5C8 and Sumichiral OA-2500 columns using 200 mM ammonium
      acetate (pH 7.0)-methanol (1:4, v/v), where 24-glucuronides were monitored with
      characteristic positive ions [M + NH4]+. The 24-glucuronides of lithocholic,
      chenodeoxycholic, deoxycholic, ursodeoxycholic and cholic acid were definitely
      characterized, in contrast to no formation of corresponding 3-glucuronides.

PMID- 9589553
TI  - Chemistry of loteprednol etabonate and related steroids. II. Reactions at ring C
      and NMR structural studies of the resulting compounds.
AB  - Several derivatives of lotoprednol etabonate (1), a soft corticosteroid
      antiinflammatory drug, are formed during the synthesis and sterilization process.
      Some of these contaminants of 1 result from side reactions taking place on the
      steroid ring C including oxidation, dehydration, chlorination and
      chlorohydroxylation. The products have been identified, synthesized, and fully
      characterized by 1H and 13C NMR spectroscopy.

PMID- 9589554
TI  - Synthesis of 4 alpha-(2-propenyl)-5,6-secocholestan-3 alpha-ol, a novel B-ring
      seco analog of the hypocholesterolemic agent 4 alpha-(2-propenyl)-5 alpha
      cholestan-3 alpha-ol.
AB  - 4 alpha-(2-Propenyl)-5 alpha-cholestan-3 alpha-ol (LY295427) was previously
      identified from a CHO cell-based assay to be a potent LDL receptor up-regulator
      and had demonstrated to be an effective agent in lowering plasma cholesterol
      levels in hypercholesterolemic hamsters. In order to investigate the effect of
      flexibility of the 3 alpha-hydroxy-bearing A-ring on the activity, 4 alpha-(2
      propenyl)-5,6-secocholestan-3 alpha-ol (11), a B-ring seco analog of LY295427, is
      thus synthesized from cholest-4-en-3-one. Test results indicate that 11 is not
      active in the CHO cell-based LDL receptor/luciferase assay at concentrations up
      to 20 micrograms/mL. The result underlines the importance of maintaining the A-B
      C-D ring rigidity of the 3 alpha-sterols in terms of binding to the putative
      oxysterol receptor.

PMID- 9589556
TI  - Synthesis of 17-oxoandrosta-3,5-dien-3-methyl sulfonate as stable analog of
      dehydroepiandrosterone sulfate.

PMID- 9589555
TI  - Effects of the 5 alpha-reductase inhibitor finasteride on serum levels of
      gonadal, adrenal, and hypophyseal hormones and its clinical significance: a
      prospective clinical study.
AB  - In the present study, we investigated the effects of a steroid 5 alpha-reductase
      inhibitor, finasteride, when given orally (5 mg/day), on the serum levels of
      gonadal, hypophyseal, and adrenal hormones and the clinical significance of these
      effects. Forty-eight patients with a mean age of 63 (range 49-81) were included
      in the study. All patients had symptoms of benign prostatic hyperplasia. Serum
      levels of testosterone, dihydrotestosterone, follicle-stimulating hormone (FSH)
      luteinizing hormone (LH), prolactin, aldosterone, cortisol, and
      dehydroepiandrosterone were determined before the study. The degree of symptoms
      in each patient and serum prostate specific antigen levels were determined
      together with uroflowmetric studies. Sexual status of the patients was also
      assessed with a self-administered questionnaire. All patients received
      finasteride, 5 mg/day, for 6 weeks. All of the above mentioned studies were
      repeated at month 3 and month 6. All of the patients had baseline hormonal values
      within the normal range. At month 3, the dihydrotestosterone level decreased by
      60%, while the testosterone level increased by 15%. FSH and LH levels decreased
      by 24% and 16%, respectively. The changes in the serum levels of these hormones
      were further evident at month 6. No significant changes were noted in the serum
      levels of prolactin, aldosterone, cortisol, and dehydroepiandrosterone. Thirty
      six patients (75%) were judged to be potent before the treatment. Finasteride
      caused erectile dysfunction in 8 patients (22%) by month 3 and in 12 (33%) by
      month 6. A substantial improvement was noted in symptoms of benign prostatic
      hyperplasia in all patients. The serum prostate specific antigen level decreased
      by 42% and 50% at month 3 and at month 6, respectively. Continued administration
      of finasteride, 5 mg/day alters the serum levels of testosterone,
      dihydrotestosterone, FSH, and LH significantly. Finasteride also causes sexual
      dysfunction in a substantial number of patients and should be offered with
      caution to patients who have an active sexual life.

PMID- 9589557
TI  - Synthesis and binding-analysis of 5E-[19-(2-bromoacetoxy)methyl]25-hydroxyvitamin
      D3 and 5E-25-hydroxyvitamin D3-19-methyl[(4-azido-2-nitro)phenyl]glycinate: novel
      C19-modified affinity and photoaffinity analogs of 25-hydroxyvitamin D3.
AB  - Synthesis of novel C19-modified affinity and photoaffinity analogs of vitamin D3
      and 25-hydroxyvitamin D3(25-OH-D3) is described. A key step in the synthesis is a
      Horner-Emmons reaction between C19-nor-cyclovitamin D3-C19-ketone or C19-nor-25
      hydroxy-cyclovitamin D3-C19-ketone and diethyl cyanomethylphosphonate.
      Competitive radioligand binding assays with human serum vitamin D-binding protein
      (DBP) and 5E-[19-(2-bromoacetoxy)methyl]25-hydroxyvitamin D3 and 5E-25
      hydroxyvitamin D3-19-methyl[(4-azido-2-nitro)phenyl]-glycinate, 25-OH-D3-analogs
      containing affinity and photoaffinity probes at C19-position, demonstrated that
      these compounds displaced radiolabeled 25-OH-D3 from the binding pocket of DBP in
      a dose-dependent manner. Thus, these affinity and photoaffinity analogs are
      potentially useful in determining the ligand binding site topographies of DBP and
      possibly the vitamin D receptor.

PMID- 9589558
TI  - Crystal structure of 11,18-oxidosteroids obtained by hypoiodination of cortisol
      acetonide.
AB  - The photochemical hypoiodination of cortisol acetonide, without neutralization of
      the excess of acidity during the work-up of the reaction, led to a mixture of 11
      beta,18-oxido-17 alpha,21-dihydroxy-4-pregnen-3,20-dione and 11 beta,19-oxido-17
      alpha,21-dihydroxy-4-pregnen-3,20-dione. Side chain cleavage of the former
      compound gave 11 beta,18-oxido-4-androsten-3,17-dione. The crystal structures of
      both of these 11 beta,18-oxidosteroids were determined by X-ray. The ring
      conformations are discussed and compared with those of aldosterone.

PMID- 9589559
TI  - Synthesis and in vitro evaluation of [carbonyl-11C]estramustine and [carbonyl
      11C]estramustine phosphate.
AB  - [carbonyl-11C]Estramustine and [carbonyl-11C]estramustine phosphate were
      synthesized from [11C]phosgene using a one pot procedure. [carbonyl
      11C]Estramustine was obtained in 31-43% decay corrected yield based on
      radioactivity trapped in the reaction vessel. The product was obtained 25 min
      after the end of radionuclide production with a specific radioactivity of 0.38
      1.11 Ci/mumol. A method was developed yielding [carbonyl-11C]estramustine
      phosphate in 29-45% decay corrected yield based on trapped radioactivity, without
      purification of the [carbonyl-11C]estramustine intermediate. The product was
      obtained within 40 min of the end of radionuclide production with a specific
      radioactivity of 0.59-0.86 Ci/mumol. Results from in vitro experiments suggest
      that because of their high nonspecific binding, the compounds are unsuitable for
      positron emission tomography as imaging agents for the estramustine binding
      protein in cancer.

PMID- 9589560
TI  - Overview of the Second International Workshop to define swine cluster of
      differentiation (CD) antigens.
AB  - The aim of the Second International Swine Cluster of Differentiation (CD)
      Workshop, supported by the Veterinary Immunology Committee (VIC) of the
      International Union of Immunological Societies (IUIS), was to standardize the
      assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte
      differentiation antigens and to define new antibody clusters. At the summary
      meeting of the workshop in July, 1995, revisions in the existing nomenclature for
      Swine CD were approved, so that the rules are now in accord with those for human
      and ruminant CD. Swine CD numbers will now be given to clusters of mAb to swine
      orthologues of human CD molecules when homology is proven by (1) suitable tissue
      distribution and lymphoid cell subset expression, (2) appropriate molecular mass
      of the antigen recognized by the mAbs, and (3) reactivity of mAbs with the cloned
      swine gene products, or cross-reactivity of the mAb on the human gene products.
      In some cases, this reactivity would not be fully proven, mainly due to the lack
      of cloned gene products; for these CD antigens, the respective clusters will be
      assigned by the prefix 'w' which will lead to 'wCD' antigens. As a result of the
      Second International Swine CD Workshop the assignment of 16 mAb to existing CD
      groups (CD2a, CD4a, CD5a, wCD6, wCD8, CD14, CD18a, wCD21, wCD25) was confirmed,
      and 2 mAb to existing swine workshop clusters (SWC). More importantly, for the
      work on the porcine immune system, was the definition of 5 new swine CD antigens,
      namely CD3 (recognized by 6 new mAb and 3 epitopes), CD16 (1 new mAb), wCD29 (2
      mAb), CD45RA (3 mAb) and CD45RC (1 new mAb). Finally, the demarcation of two new
      SWC molecules in swine, SWC8 (2 mAb) and SWC9 (2 mAb) was confirmed.

PMID- 9589561
TI  - Immunoprecipitation studies of monoclonal antibodies submitted to the Second
      International Swine CD Workshop.

PMID- 9589562
TI  - Summary of the first round analyses of the Second International Swine CD
      Workshop.
AB  - The reactivity of 176 monoclonal antibodies (mAb) submitted to the Second
      International Swine CD Workshop, together with 19 internal standards, was
      analyzed by flow cytometry on 16 different cell types as a means of establishing
      the proper cell subset for later detailed clustering analyses. The exact CD
      subset reactivity of the 19 internal standard mAb had been characterized in the
      First International Swine CD Workshop. The flow cytometric analyses resulted in
      40 data sets which were then subjected to statistical clustering using the
      Leukocyte Typing Database IV (LTDB4) software. As result of this work, 22
      clusters were defined. After review of these results, panels of mAb from the
      defined first round clusters were assigned to cell subsets. The respective mAb in
      those first round clusters were then distributed to subset group researchers for
      further examination during the second round of the workshop.

PMID- 9589563
TI  - Summary of workshop findings for antibodies reacting with porcine T-cells and
      activation antigens: results from the Second International Swine CD Workshop.
AB  - After initial evaluation of the 176 new and 19 control monoclonal antibodies
      (mAb) submitted to the Second International Swine CD Workshop, 57 were assigned
      to the T-cell/activation marker subgroup. These 57 mAb were further analyzed
      using flow cytometry on whole blood lymphocytes, splenocytes, Peyer's patch
      lymphocytes, in vitro cell lines, broncho-alveolar lavage cells, Con A and PHA
      blasts, fetal cell populations, and by 2-color flow cytometry against mAb to
      porcine CD2, CD4, and CD8. Finally, the molecular weights of the target antigens
      were characterized when possible. As a result of these analyses, 23 mAb were
      distributed into 7 CD clusters. Newly confirmed mAb assignments included: two
      CD2; one CD4; two CD5; one wCD6; and one wCD25. Three new mAb were found that
      reacted with wCD8, one of which defined a new epitope, wCD8c. For the first time,
      mAb against porcine CD3 were identified, including 6 mAb that reacted with three
      different epitopes. Several new mAb reacted with antigens whose expression varied
      depending on the activation state of the test cell. These will require further
      characterization in order to assign a CD number.

PMID- 9589564
TI  - Analyses of monoclonal antibodies reacting with porcine CD3: results from the
      Second International Swine CD Workshop.
AB  - Among the 57 monoclonal antibodies (mAb) analyzed within the T-cell group from
      the Second Swine CD Workshop, six mAb fell within clusters T10 and T11 (No. 088,
      STH164; No. 148, FY1A3; No. 149, FY2C1; No. 150, FY1H2; No. 151, FY2A11; No. 169,
      BB23-8E6). The mAb within these two groups gave a similar appearance on flow
      cytometry and stained all peripheral blood T-cells as defined by CD4 and wCD8
      staining. All six mAb precipitated a 24 kDa protein. On the basis of inhibition
      analyses performed as part of the workshop and from published data, the mAb
      define at least three epitopes. There is only minimal stimulation of resting
      peripheral lymphocytes, but four of the mAb produce strong stimulation in the
      presence of PMA. With the exception of STH164, all have been shown to react with
      CD3 epsilon-transfected COS cells. The new mAb, therefore, react with three
      epitopes on porcine CD3 epsilon designated CD3a (BB23-8E6, FY2A11), CD3b (FY1A3,
      FY2C1), and CD3c (FY1H2). mAb STH164 appears to be reactive with another epitope,
      however, since its reactivity with CD3 has not been confirmed it is designated as
      wCD3.

PMID- 9589565
TI  - Analyses of monoclonal antibodies reacting with porcine CD5: results from the
      Second International Swine CD Workshop.
AB  - Among the 57 monoclonal antibodies analyzed within the T-cell group, three mAbs
      fell within cluster T13 including the CD5a standard b53b7 (No. 174). The two new
      mAbs 1H6/8 (No. 058) and BB6-9G12 (No. 166) both precipitated 55 and 60 kDa
      proteins that were of similar molecular weights as the standard. Staining
      patterns on the various cell types were similar. Both new antibodies inhibited
      the binding of the CD5a reference mAbs b53b7 to peripheral lymphocytes. These
      mAbs, therefore both react with the CD5a epitope bringing the number of anti
      porcine CD5 mAbs to eight, all of which appear to recognize the same epitope.

PMID- 9589566
TI  - Porcine CD5 gene and gene product identified on the basis of inter-species
      conserved cytoplasmic domain sequences.
AB  - Analysis of published CD5 amino acid sequences identified conserved sequences
      with potentially immunogenic epitopes. To obtain anti-porcine CD5, synthetic
      peptides representing conserved sequences identified in mouse, human, cattle and
      sheep CD5 cytoplasmic tail domains were linked to KLH and used to immunize
      rabbits. Anti-synthetic peptide serum reacted with an antigen extracted from
      porcine lymphocyte membrane which was consistent in size (67 kDa) with CD5.
      Murine monoclonal anti-porcine wCD5 (b53b7) and the anti-CD5 synthetic peptide
      serum react with the same ligand confirming that porcine wCD5 has conserved amino
      acid sequences similar to those of CD5 of several species. Analysis of porcine
      genome for CD5 gene sequences by PCR was conducted to verify the presence of CD5
      like genes. Oligomeric primers were designed to identify CD5-like sequences by
      polymerase chain reaction in pigs and other species. Amplified DNA similar in
      size to that predicted for CD5 elements were amplified from a variety of animal
      genomes including that of pig. The porcine-derived fragment was cloned and shown
      to be 96% similar to mouse CD5. The use of published CD sequences for prediction
      of immunogenic peptides has provided a complimentary alternative to the more
      traditional approaches to production of CD-specific antibodies.

PMID- 9589567
TI  - Analyses of monoclonal antibodies reacting with porcine wCD6: results from the
      Second International Swine CD Workshop.
AB  - Among the 57 monoclonal antibodies analyzed within the T-cell group of the Second
      International Swine CD Workshop, one mAb fell within cluster T14a that included
      the CD6 standard a38b2 (No. 175). The new mAb MIL8 (No. 082) and a38b2 both
      precipitated from activated T-cells a 150 kDa monomeric protein. Staining
      patterns on the various cell types were similar. There was no inhibition of
      binding of either mAb to peripheral blood T-cells with the opposite mAb. The new
      mAb, MIL8, reacts with a separate epitope on porcine wCD6.

PMID- 9589568
TI  - Report on the analyses of mAb reactive with porcine CD8 for the second
      international swine CD workshop.
AB  - Based on an analysis of their reactivity with porcine peripheral blood
      lymphocytes (PBL), only three of the 57 mAbs assigned to the T cell/activation
      marker group were grouped into cluster T9 along with the two wCD8 workshop
      standard mAbs 76-2-11 (CD8a) and 11/295/33 (CD8b). Their placement was verified
      through the use of two-color cytofluorometry which established that all three
      mAbs (STH101, #090; UCP1H12-2, #139; and PG164A, #051) bind exclusively to CD8+
      cells. Moreover, like the CD8 standard mAbs, these three mAbs reacted with two
      proteins with a MW of 33 and 35 kDa from lymphocyte lysates and were, thus, given
      the wCD8 designation. Because the mAb STH101 inhibited the binding of mAb 76-2-11
      but not of 11/295/33, it was given the wCD8a designation. The reactivity of the
      other two new mAbs in the T9 cluster with the various subsets of CD8+ lymphocytes
      were distinct from that of the other members in this cluster including the
      standards. Although the characteristic porcine CD8 staining pattern consisting of
      CD8low and CD8high cells was obtained with the mAb UCP1H12-2, a wider gap between
      the fluorescence intensity of the CD8low and CD8high lymphocytes was observed. In
      contrast, the mAb PG164A, not only exclusively reacted with CD4-/CD8high
      lymphocytes, but it also failed to recognize CD4/CD8 double positive lymphocytes.
      It was concluded that this mAb is specific for a previously unrecognized CD8
      epitope, and was, thus, given the wCD8c designation. A very similar reactivity
      pattern to that of PG164A was observed for two other mAbs (STH106, #094; and
      SwNL554.1, #009). Although these two mAbs were not originally positioned in the T
      cell subgroup because of their reactivity and their ability to inhibit the
      binding of PG164A, they were given the wCD8c designation. Overall, five new wCD8
      mAbs were identified. Although the molecular basis for the differences in PBL
      recognition by these mAbs is not yet understood, they will be important in
      defining the role of CD8+ lymphocyte subsets in health and disease.

PMID- 9589569
TI  - Analysis of monoclonal antibodies that recognize gamma delta T/null cells.
AB  - Thirty two monoclonal antibodies (mAbs) from the first round of analysis in the
      Second International Swine CD Workshop were placed together with additional mAb
      derived from the first workshop in the null cell panel for further evaluation.
      Preparations of peripheral blood leukocytes, concanavalin A stimulated peripheral
      blood mononuclear cells, and spleen cells were used in flow cytometric analyses.
      Nineteen mAbs identified molecules that were not expressed on null cells, not
      lineage specific, or recognized activation molecules. Sixteen mAbs including
      control mAbs were identified that were specific for null cells. One of the latter
      mAbs, 041 (PGBL22A), that recognizes a determinant on a constant region of
      porcine gamma delta TcR established the majority of null cells are gamma delta T
      cells. Use of this mAb in further comparisons demonstrated the gamma delta T cell
      population is comprised of two major subpopulations, one negative and one
      positive for CD2. Two color analyses demonstrated that 11 of the mAbs formed a
      broad cluster that included control mAbs 188 (MAC320) that defined the CD2
      negative SWC6 cluster in the first workshop and mAb 122 (CC101) that might
      recognize an orthologue of bovine WC1 and nine mAbs that recognize determinants
      on one or more molecules with overlapping patterns of expression on subsets of
      CD2- gamma delta T cells. Two groups of mAbs formed the previously identified
      subset clusters SWC4 and SWC5. Two new mAbs formed a third subcluster. Three mAbs
      did not form clusters. Three mAbs predicted to recognize TcR in the first
      workshop (020 [PT14A], 021 [PT79A], and 022 [MUC127A]) and mAb PGBL22A were shown
      to immunoprecipitate a 37, 40 kDa heterodimer.

PMID- 9589571
TI  - Porcine myelomonocytic markers: summary of the Second International Swine CD
      Workshop.
AB  - Forty five mAbs submitted to the Second International Swine CD workshop were
      analyzed by six different laboratories for their possible reactivity with porcine
      myelomonocytic cells using flow cytometry and immunohistochemistry. As a result
      of these analyses, a new swine workshop cluster, SWC9, composed of two mAbs that
      recognize an antigen selectively expressed on mature macrophages, was defined. In
      addition, several mAbs were identified, allowing the differentiation of
      granulocytes from monocytes/macrophages, or monocytes from macrophages. Further
      work is required to identify the antigen recognized by these mAbs. Nevertheless,
      they should already prove useful for the identification of different stages in
      the macrophage maturation/differentiation, and will certainly aid analyses on the
      complexity of the mononuclear phagocyte system in the pig. Finally, the cross
      reactivity of three anti-human CD14 mAbs with porcine myelomonocytic cells was
      established in this workshop.

PMID- 9589570
TI  - Monoclonal antibodies putatively identifying porcine B cells.
AB  - Comparison was made of the binding of 38 test and three standard monoclonal
      antibodies (mAbs) to B cells from various pig lymphoid tissues by flow cytometry
      (FCM) and immunohistochemistry. Some mAbs were also tested on B cells from foetal
      pig tissues. Twenty of the new mAbs bound, though to variable degrees, to porcine
      B cells but only three were given cluster assignations: C35 (#147) and BB6-11C9
      (#167) were assigned to wCD21 and 2F6/8 (#057) was assigned to SWC7.

PMID- 9589572
TI  - Workshop studies with monoclonal antibodies identifying a novel porcine
      differentiation antigen, SWC9.
AB  - Two monoclonal antibodies (mAb) within cluster M4 of the myeloid section of the
      Second International Swine CD Workshop, C4 (No. 144) and PM18-7 (No. 192), showed
      reactivity with thymocytes and among cells of myelomonocytic origin with mature
      macrophages but not with monocytes and granulocytes. Both mAb recognize a protein
      showing two bands of 205 kDa and 130 kDa under both reducing and non-reducing
      conditions. Although epitope mapping with these mAb could not be performed, this
      cluster received the SWC9 designation.

PMID- 9589573
TI  - Summary of workshop findings for porcine adhesion molecule subgroup.
AB  - Fifty-nine monoclonal antibodies (mAb) were assigned to the adhesion section of
      the Second International Swine CD Workshop. They were analysed for their
      reactivity to selected lymphoid cell populations, as well as to non-lymphoid cell
      lines. Cell lysate ELISAS and Western Blot analyses were also carried out. As a
      result, thirteen separate cluster groups emerged (p > 0.95). Workshop assignments
      for adhesion molecules were made: wCD29/49 for mAbs UCP1D2 (#133) and FW4-101
      (#165), and PNK-I (#194) and MUC76A (#025) could be assigned to wCD18. For one
      cluster (FQ1D7, #161 and 2F4, #069) the cellular distribution and MW were
      characteristic for MHC Class II, and another cluster comprising several
      antibodies which appeared to recognise MHC Class I. Other clusters could not be
      assigned to cell surface structures known to be linked to cellular adhesion,
      however, two further antibodies, 335-2 (#112) and FG1F6 (#156), could be added to
      SWC1, and the new SWC8 was defined by MIL3 (#077) and MUC20A (#029), binding a
      ligand of 29-32 kDa. Clustering for these two antibodies was confirmed by
      blocking studies. The cellular distribution is known for MIL3, recognising an
      epitope present on granulocytes, B cells, and a subset of T cells expressing CD8
      at high intensity.

PMID- 9589574
TI  - Definition of the specificity of monoclonal antibodies against porcine CD45 and
      CD45R: report from the CD45/CD45R and CD44 subgroup of the Second International
      Swine CD Workshop.
AB  - Swine cell binding analyses of a set of 48 monoclonal antibodies (mAbs),
      including eleven standards, assigned to the CD44 and CD45 subset group of the
      Second International Swine CD Workshop yielded 13 clusters. Although none of
      these corresponded to CD44, seven mAbs formed a cluster which was identified as
      being specific for restricted epitopes of CD45 (CD45R). In addition, a T-cell
      subset specific cluster comprised of four mAbs was also identified. Two mAbs
      (STH106 and SwNL 554.1) reacted exclusively with CD8 bright lymphocytes, the
      other two (2B11 and F01G9) with a subset of CD4 lymphocytes. The other 10
      clusters were either specific for MHC-class I like molecules or overlapped with
      clusters identified by the adhesion molecule subgroup and are therefore just
      briefly discussed in this report. The specificity of all the mAbs in the CD45R
      cluster was verified by their ability to immunoprecipitate distinct proteins and
      to react with CHO cells expressing individual isoforms of CD45. Three CD45R mAbs
      (3a56, MIL5, -a2) did react with a 210 kDa isoform(s), while another three
      (STH267, FG2F9, 6E3/7) only recognized a 226 kDa isoform(s). The remaining one
      (MAC326) precipitated both a 210 and 226 kDa protein. The specificity of all the
      mAbs in the CD45R cluster, and of the CD45 common mAbs, was confirmed by their
      reactivity with CHO cells transfected with cDNAs encoding the extracellular and
      transmembrane portions of distinct CD45R isoforms. Those mAbs recognizing a 210
      kDa protein reacted with CHO cells expressing the CD45RC isoform, while those
      capable of precipitating a 226 kDa, but not the 210 kDa, polypeptide recognized
      CHO cells expressing either the CD45RAC and the relatively rare CD45RA isoform.
      MAC326 was unique in its inability to react with CHO cells engineered to produce
      the CD45RC and CD45RAC isoforms. Thus, three mAbs (6E3/7, STH267, and FG2F9)
      appear to be specific for an epitope(s) encoded by the A exon, while one (MAC326)
      recognizes a determinant encoded by the C exon. The remaining three mAbs (3a56, 
      a2, MIL5) are apparently specific for an epitope(s) which results from the fusion
      of the C exon to the invariant leader sequence and is destroyed by inclusion of
      the A exon. All three CD45 common mAbs, K252.1E4, MAC323 and 74.9.3, did react
      with the CHO cells lines expressing either the CD45RA, CD45RC, CD45RAC or CD45RO
      isoforms, but not with untransfected CHO cells. When the natural expression of
      CD45 isoforms was examined by reacting lymphocytes with CD45R mAbs, a high level
      expression of isoforms containing the A exon-generated domain was detected in all
      B cells while the majority of CD4+ T cells had undetectable or lower expression
      density of this protein than B cells. In contrast, the density of expression of
      the CD45 isoform(s) containing the C exon-generated domain ranged from
      undetectable to high in CD4+ T cells whereas the amounts were approximately ten
      fold lower in B cells. Overall this panel of CD45 mAbs will be very useful in
      analyzing the maturation and differentiation of swine lymphoid cells subsets.

PMID- 9589575
TI  - Determination of the specificity of CD45 and CD45R monoclonal antibodies through
      the use of transfected hamster cells producing individual porcine CD45 isoforms.
AB  - The exclusive presence of the tyrosine phosphatase, CD45, on the surface of
      hematopoietic cells coupled with the differential expression of its various
      isoforms has enabled the selection of lymphocyte subsets based on their
      reactivity with monoclonal antibodies (mAbs) specific for one or more CD45
      species. As a prelude to defining the specificity of anti-porcine CD45 mAbs for
      this purpose, Chinese hamster ovary cells were transfected with constructs
      containing cDNAs encoding the extracellular and transmembrane domains of four pig
      CD45 isoforms. Cells expressing only one of the three predominant types (CD45RO,
      CD45RC, and CD45RAC) or the minor species (CD45RA) of porcine CD45 on their
      surface were sorted based on positive reactivity with the CD45 mAb K252.1E4.
      Initially, these CD45+ cells were used as a source of antigen when determining
      the specificities of nine mAbs, which had been identified during the First and
      Second International Swine CD Workshops as being reactive with porcine CD45.
      Later, cloned cell lines were established and phenotypically verified for the
      production of the correct CD45 transcript by RT-PCR. Binding of two more mAbs (74
      9-3 and 10-14-1) in addition to the original mAb panel to these cell lines was
      assessed by using a cell ELISA in lieu of one-color flow cytometry. Despite
      differences in detection methodology, identical mAb binding results were
      obtained. As anticipated, CD45 mAbs K252.1E4, MAC 323, and 74-9-3 which recognize
      an epitope(s) in the common portion of porcine CD45, reacted with cells
      expressing any one of the four isoforms but not with the parental CHO cells. In
      contrast, none of the restricted (CD45R) mAbs bound to cells producing the CD45RO
      isoform which lacks any of the alternate extracellular regions. However, three of
      these mABs (6E3/7, FG2F9 and STH267) did react specifically with the CD45RA and
      CD45RAC isoforms, indicating their specificity for an epitope(s) encoded by the
      CD45 A exon. The other four CD45R mAbs (MAC326, 3a56, MIL5, and -a2) recognized
      the CD45RC isoform. Interestingly, only CD45R mAb MAC326 also bound to cells
      expressing the CD45RAC isoform, suggesting that the epitope(s) recognized by the
      other three may have arisen due to the juncture of the invariant 5' leader
      sequence with the CD45C exon. The eleventh mAb (10-14-1) was unique in that it
      did not react with any of the expressed CD45 isoforms. This inability coupled
      with the previously demonstrated recognition of a 240 kDa protein suggests that
      it may be specific for CD45RABC. Overall, this panel of CD45R mAbs should prove
      useful for obtaining functionally distinct subpopulations of B and T lymphocytes.

PMID- 9589576
TI  - Cross-reactivity of human leucocyte differentiation antigen monoclonal antibodies
      on porcine cells.
AB  - Thirty-six subpanels of monoclonal antibodies (mAbs) supplied to the Fifth
      International Workshop on Human Leucocyte Differentiation Antigens were assayed
      on porcine peripheral blood leucocytes for cross-reactivity. Sixty-two of the 752
      mAbs-stained porcine cells. These mAbs identified 30 different CD groups and will
      be valuable reagents in the field of porcine immunology.

PMID- 9589577
TI  - Reactivity of workshop monoclonal antibodies on paraformaldehyde-fixed porcine
      blood mononuclear cells.
AB  - One hundred sixty-four monoclonal antibodies (mAbs) of the second international
      swine CD workshop were tested for their reactivity with porcine blood mononuclear
      cells before and after fixing the cells with varying concentrations of
      paraformaldehyde (PFA) (1, 5 and 10 g l-1). A total of 38 (out of 134) positive
      reacting mAbs were significantly affected in their binding behavior on fixed
      cells. Modulation was seen as reduction in binding (staining intensity and/or %
      positive cells, n = 18) or in elevated values (n = 20). Modified mAb binding
      occurred after fixing cells with 5 to 10 g l-1 PFA.

PMID- 9589578
TI  - Crossreactivity of workshop monoclonal antibodies with canine blood leukocytes.
AB  - A selection of 164 monoclonal antibodies for determinants on porcine cells were
      tested on canine leukocytes by flow cytometry. Eighteen mAbs proved to be
      crossreacting and 16 of these reacted uniformly with cells of three unrelated
      dogs while two displayed a polymorphic reaction pattern.

PMID- 9589579
TI  - Flow cytometry data included in first round cluster analysis.
AB  - Tables 1-16 contain the results of flow cytometry analyses of 18 different cell
      types labelled with all 176 monoclonal antibodies submitted to the Second
      International Swine CD workshop. The 19 standards (mAb #171-#189) characterized
      for their specificity in the first workshop served as controls. Data derived from
      40 different analyses are presented as % positive cells.

PMID- 9589580
TI  - Sequence analysis of MHC class I alpha 2 domain exon variants in one diploid and
      two haploid Atlantic salmon pedigrees.
AB  - Genetic diversity in the second domain exon of Atlantic salmon (Salmo salar)
      major histocompatibility complex (Mhc) class I was investigated in two dams and
      nine of their haploid offspring by means of polymerase chain reaction (PCR) and
      DNA sequence analysis. A similar study was also performed on nine diploid
      offspring from one of these dams. The complex segregation patterns and sequence
      similarities between variants make definitive allele, haplotype and locus
      assignments difficult. There are, however, indications of six Mhc-Sasa class I
      loci and a fairly well-defined haplotype of four variants. One non-polymorphic
      variant present in most specimens could be a salmon analogue to the human non
      classical loci.

PMID- 9589581
TI  - Cloning of canine rom-1 and its investigation as a candidate gene for generalized
      progressive retinal atrophies in dogs.
AB  - Generalized progressive retinal atrophy (gPRA) represents a genetically
      heterogenous group of retinal degenerations affecting pedigree dogs. Currently,
      we are using a candidate gene approach in an attempt to identify mutations
      causing gPRA in dogs. Here we report the cloning, sequencing and analysis of
      canine rom-1, a structural gene of the rod photoreceptor. Single-stranded
      conformation polymorphism (SSCP) analysis was used to look for polymorphisms
      segregating with gPRA in the English cocker spaniel, Labrador retriever,
      miniature poodle, miniature long-haired dachshund, Tibetan terrier, miniature
      schnauzer, Cardigan Welsh corgi and Irish wolfhound. Further investigation
      involved DNA sequencing and restriction fragment length polymorphism (RFLP)
      analysis. Our studies revealed the presence of three polymorphisms, none of which
      segregated with disease phenotype. Haplotype analysis identified four rom-1
      alleles. Our results indicate that rom-1 is unlikely to be a cause of gPRA in the
      breeds of dog examined.

PMID- 9589582
TI  - Chicken microsatellite markers isolated from libraries enriched for simple tandem
      repeats.
AB  - The total number of microsatellite loci is considered to be at least 10-fold
      lower in avian species than in mammalian species. Therefore, efficient large
      scale cloning of chicken microsatellites, as required for the construction of a
      high-resolution linkage map, is facilitated by the construction of libraries
      using an enrichment strategy. In this study, a plasmid library enriched for
      tandem repeats was constructed from chicken genomic DNA by hybridization
      selection. Using this technique the proportion of recombinant clones that cross
      hybridized to probes containing simple tandem repeats was raised to 16%, compared
      with < 0.1% in a non-enriched library. Primers were designed from 121 different
      sequences. Polymerase chain reaction (PCR) analysis of two chicken reference
      pedigrees enabled 72 loci to be localized within the collaborative chicken
      genetic map, and at least 30 of the remaining loci have been shown to be
      informative in these or other crosses.

PMID- 9589583
TI  - AFLP markers for DNA fingerprinting in cattle.
AB  - This work reports on use of the recently described amplified fragment length
      polymorphism (AFLP) technology for DNA fingerprinting in cattle. The AFLP
      technology produces molecular markers through the high-stringency polymerase
      chain reaction (PCR)-amplification of restriction fragments that are ligated to
      synthetic adapters and amplified using primers, complementary to the adapters,
      which carry selective nucleotides at their 3' ends. While, for plants, the double
      digestion of genomic DNA with EcoRI and MseI is suggested, in mammals the enzyme
      combination EcoRI/TaqI produces clearer and more polymorphic AFLP patterns. In a
      sample of 47 Italian Holstein genotypes, 16 EcoRI/TaqI primer combinations
      identified 248 polymorphic bands in a species known for its low level of
      restriction polymorphism. In spite of the low information content carried by each
      AFLP polymorphism (average polymorphism information content = 0.31), the number
      of fragments revealed by each primer combination increased significantly the
      level of genetic information gained in each experiment. AFLP patterns are
      reproducible in independent experiments and polymorphic fragments segregate in
      cattle families according to Mendelian rules.

PMID- 9589584
TI  - New microsatellite markers in chicken optimized for automated fluorescent
      genotyping.
AB  - We have isolated and developed 180 new polymorphic chicken microsatellite
      markers. In addition, primers have been developed for 91 microsatellites derived
      from the GenBank sequence database (isolated by the laboratory of Terry Burke,
      Leicester University), of which 89 were polymorphic, and six existing polymorphic
      markers (HUJ) have been modified. The primer sequences were designed to allow
      optimal performance of the markers, in sets containing multiple microsatellites,
      on ABI sequencers. The average number of alleles for the 275 polymorphic markers
      described was 4.0. Of these markers, 93% were polymorphic in the Wageningen
      resource population whereas 57% of the markers were polymorphic in the East
      Lansing reference population and only 44% could be mapped in the Compton
      reference population. The microsatellite markers described in this paper, in
      combination with the microsatellite markers published previously, are
      particularly well suited for performing a total genome scan for the detection of
      quantitative trait loci (QTL).

PMID- 9589585
TI  - A single base transversion in the flanking region of an equine microsatellite
      locus affects amplification of one allele.
AB  - The equine dinucleotide microsatellite HMS7 is part of a microsatellite panel
      utilized in a parentage verification programme at the Veterinary Genetics
      Laboratory (Davis, California, USA). Apparent non-Mendelian inheritance was noted
      when a Quarter Horse mare was excluded as the parent of two offspring based on
      analysis of the HMS7 locus. The mare's DNA type qualified her as a parent of the
      offspring at an additional 20 microsatellite loci. The three animals appeared
      homozygous for HMS7 with each possessing an allele different from that of the
      other two animals. Polymerase chain reaction primers designed to bind outside the
      published primer-binding sites amplified an additional shared allele in all three
      horses, which qualified the mare as the dam of the two offspring. Sequencing of
      this newly detected allele revealed a C to A transversion in one of the published
      primer-binding regions. Apparent non-Mendelian inheritance at the HMS7 locus has
      been encountered in an additional 26 Quarter Horse parentage cases. In all
      instances, the lack of amplification and resultant 'null' allele was shown to be
      caused by the same transversion.

PMID- 9589586
TI  - Sequence polymorphism in the bovine major histocompatibility complex DQB loci.
AB  - Polymorphism in DQB sequences of the bovine major histocompatibility complex was
      investigated in 22 British Friesian cattle. The first domain exon was amplified,
      cloned and sequenced. Eight different sequences were identified, six of which had
      not been identified previously. The high proportion of novel sequences suggests
      that additional polymorphisms within the DQB loci remain to be discovered in this
      breed. One sequence was present in at least 21 of the 22 cattle. This sequence,
      or a closely related sequence, has also been found in American Holstein Friesian,
      Swedish Red and White and Japanese Black cattle. The remarkably high sequence
      conservation suggests that the bovine DQB region may contain a locus with a low
      level of polymorphism and be more similar to the human DQB region than previously
      supposed. One sequence with three widely spaced frameshift insertions appeared to
      be a pseudogene.

PMID- 9589587
TI  - Some new variants of serum protease inhibitors in Meishan pigs.
AB  - Serum samples of Meishan (13 animals) and Meishan x Wild Boar crosses (361
      animals) were analysed by means of two-dimensional electrophoresis. Some new
      variants in protease inhibitor systems PO1A, PO1B and PI2 are reported.

PMID- 9589588
TI  - Mapping genes located on human chromosomes 2 and 12 to porcine chromosomes 15 and
      5.
AB  - Informative microsatellites associated with two genes on HSA12 (lysozyme, LYZ;
      tumour necrosis factor receptor, TNFR) and one gene on HSA2 (glutamic acid
      decarboxylase 1, GAD1) were mapped in the US Meat Animal Research Center (MARC)
      swine reference population and the physical assignment of a-lactalbumin (LALBA)
      was determined. A comparative map for HSA2 and HSA12 with SSC15 and SSC5,
      respectively, was developed by combining the results from this study with
      published type I loci mapped in both species. One rearrangement between HSA2 and
      SSC15 was detected while the number of rearrangements between HSA12 and SSC5 were
      numerous. These results indicated that conservation of synteny does not imply a
      conservation of gene order and that additional type I markers need to be mapped
      in the pig to fully understand the chromosomal rearrangements that occurred
      during the evolution of mammals.

PMID- 9589589
TI  - Characterization of twelve new horse microsatellite loci: AHT12-AHT23.

PMID- 9589590
TI  - Assignment of the canine microsatellite CanBern6 to the canine chromosome group
      22 to 38.

PMID- 9589591
TI  - RFLPs in sheep detected with human cDNA probe for interferon-induced MX1 protein.

PMID- 9589593
TI  - OarSHP1 and OarSHP2: two ovine microsatellite markers and their chromosomal
      assignments.

PMID- 9589592
TI  - A highly polymorphic minisatellite locus (KBMS2) in bovine.

PMID- 9589594
TI  - A ScaI polymorphism at the ovine monoamine oxidase A locus (MAOA).

PMID- 9589595
TI  - Linkage between growth hormone (GH1) and solute carrier family 4 anion exchanger
      member 1 (SLC4A1) is conserved between birds and mammals.

PMID- 9589596
TI  - Two new polymorphic porcine microsatellites, S0533 and S0534.

PMID- 9589597
TI  - A polymorphic TG repeat present within the bovine STAT5A gene.

PMID- 9589598
TI  - SSCP identifies bovine CSN1S1D.

PMID- 9589599
TI  - Identification and characterization of a SSCP marker in the canine signal
      sequence receptor beta subunit gene.

PMID- 9589600
TI  - Polymorphism at the porcine LEPR gene detected by PCR-DGGE.

PMID- 9589602
TI  - Novel insecticidal peptides from Tegenaria agrestis spider venom may have a
      direct effect on the insect central nervous system.
AB  - Fractionation of venom from an agelenid spider, Tegenaria agrestis, resulted in
      the isolation of a family of three peptides with potent insecticidal activity.
      These peptide toxins, TaITX-1, -2, and -3, whose sequences were revealed from
      cloned cDNAs, each consist of 50 amino acid residues, six of which are cysteines.
      They appear to be amidated at their C-termini and exhibit greater than 90%
      sequence identity. Unlike other reported spider toxins, the TaI toxins are
      processed from precursors containing no propeptide sequences. In lepidopteran
      larvae and corn rootworm beetles, the insecticidal Tegenaria toxins caused an
      unusual excitatory symptomatology with 50% paralytic doses ranging from 0.23 to
      2.6 nmol/g. In a series of electrophysiological experiments performed in house
      fly larvae, these toxins caused an elevated rate of firing from central nervous
      system neurons. No significant effects were found when any peripheral sensory or
      motor systems were examined. Thus, it appears that the TaI toxins may act in a
      fashion not previously reported for insecticidal peptide toxins; they may act
      directly on the insect central nervous system.

PMID- 9589601
TI  - Structure-function analysis of Lymantria testis ecdysiotropin: a search for the
      active core.
AB  - A structure-function study was performed on the synthetic 21 residue
      neuropeptide, Lymantria testis ecdysiotropin (LTE), originally isolated from
      brains of Lymantria dispar pupae. The peptide induces ecdysteroid synthesis by
      testis sheaths of various lepidopteran species. LTE, as well as synthetic LTE 1
      11, 11-21, and 11-15, stimulated synthesis in larval and pupal testes of
      Lymantria dispar at concentrations of 10(-9) to 10(-15) M; LTE 16-21 was weakly
      active, and an elongated LEU-LTE was inhibitory to synthesis at all but extremely
      low concentrations (10(-15) M). Since the sequence and polarity of residues in
      LTE 1-11, 11-15, and 11-21 are quite different, several parts of the molecule
      must activate receptors which initiate the cascade, resulting in ecdysiogenesis
      in Lepidopteran testes.

PMID- 9589604
TI  - Characterization of satellite cells derived from chickens with the low score
      normal (LSN) muscle weakness.
AB  - Myogenic satellite cell clones were established from the pectoralis major muscle
      of chickens with the low score normal (LSN) muscle weakness and controls. The
      percentage of cells which attached to substrata and began to proliferate was
      higher for the control line than the LSN line (55% vs 30%). Furthermore, of those
      clones which initiated growth, 63% of the control cells and only 32% of the LSN
      cells proliferated to confluence in 25 cm2 tissue culture flasks. Proliferation
      rates were significantly lower with LSN satellite cells than with controls (p <
      0.05). LSN satellite cells were less responsive to the mitogenic effects of
      chicken serum (p < 0.05) and differentiation rates were lower compared with
      controls (p < 0.05). There was a greater (p < 0.05) number of insulin-like growth
      factor receptors on LSN satellite cells compared with controls. The IGF receptor
      binding affinities (Kds) between the two cell lines were similar (p > 0.05). The
      results suggest that a defect in satellite cell physiology may contribute to the
      skeletal muscle weakness seen in the LSN line.

PMID- 9589603
TI  - Model sclerotization studies. 4. Generation of N-acetylmethionyl catechol adducts
      during tyrosinase-catalyzed oxidation of catechols in the presence of N
      acetylmethionine.
AB  - Incubation of catechol with mushroom tyrosinase in the presence of N
      acetylmethionine resulted in the generation of an adduct. This product was
      identified to be N-acetylmethionyl catechol, on the basis of spectral
      characteristics and well-characterized chemical reaction of o-benzoquinone with N
      acetylmethionine. Enzyme-catalyzed oxidation of catechol and the subsequent
      nonenzymatic addition of the resultant quinone to N-acetylmethionine accounted
      for the observed reaction. That the reaction is not confined to catechol alone,
      but is of general occurrence, can be demonstrated by the facile generation of
      similar adducts in incubation mixtures containing N-acetylmethionine, tyrosinase,
      and different N-acetylmethionines, such as 4-methylcatechol and N-acetyldopamine.
      Attempts to duplicate the reaction with insect cuticular phenoloxidases were not
      successful, as the excess N-acetylmethionine used in the reaction inhibited their
      activity. Nevertheless, occurrence of this nonenzymatic reactivity. Nevertheless,
      occurrence of this nonenzymatic reaction between N-acetylmethionine and mushroom
      tyrosinase-generated quinones indicates that a similar reaction between
      enzymatically generated quinones in the cuticle with protein-bound methionine
      moiety is likely to occur during in vivo quinone tanning as well.

PMID- 9589605
TI  - Inhibition of connexin 43 synthesis by antisense RNA in rat glioma cells.
AB  - The 9L rat glioma cells communicate via gap junctions which are formed of
      connexin 43. The gap junctional communication was inhibited in these cells by
      transfecting them with an antisense Cx43 DNA construct, and its effect on their
      growth rate was investigated. This construct was induced by a Zn(2+)-inducible
      metallothionein promoter. Results showed that the induction of antisense RNA
      expression in rat 9L glioma cells produced the loss of gap junctions which was
      reflected in the loss of gap junctional communication. By inducing the antisense
      construct with zinc acetate, and using specific antibodies to connexin 43, the
      synthesis of this connexin was inhibited in the transfected cells and gap
      junctions were lost on the cell-cell appositions. There was no such effect on the
      untransfected cells. The loss of gap junctions at cell-cell appositions also
      correlated with the loss of Lucifer yellow fluorescent dye transfer between the
      cells. The effect of loss of gap junctions on the growth rate of the cells was
      assessed. In spite of the drastic decrease in the number of gap junctions between
      cells, their growth rate was only approximately 20% less than that of the
      transfected but non-induced cells. Therefore, gap junction communication is not
      negatively related to the rate of growth of these cells.

PMID- 9589606
TI  - CD45RA and CD45RO isoform expression on intrahepatic T-lymphocytes in chronic
      hepatitis C.
AB  - A liver tissue recruitment of antigen-specific cytotoxic cells has been reported
      in chronic hepatitis C virus (HCV) infection, but whether they really play a role
      in viral clearance is still a matter of investigation. To further evaluate T-cell
      involvement in HCV-induced hepatic disease, the authors analysed, in a cohort of
      chronic hepatitis C patients, the intrahepatic T-cell expression of CD45 isoforms
      by using specific monoclonal antibodies. Within hepatic specimens, CD45RA+
      (naive) cell frequency at the portal tract level was significantly higher than
      that exhibited at lobular level. At the same time, a large number of CD45RO+
      (memory) cells was found at periportal sites in comparison with the lobular
      counterpart. The evaluation of CD45RA and CD45RO isoform topographical
      distribution in relation to CD4+ and CD8+ lymphocytes, as determined on serial
      sections, showed that CD45RA antigen expression was predominantly coexpressed
      with CD4+ lymphocytes at the portal tract level, and the CD45RO phenotype with
      CD8 structure at the lobular and periportal sites. The levels of CD45 isoforms
      did not show any correlation with biological and/or histological disease
      activities. The results suggest that a liver recruitment of both naive and memory
      cells occurs during chronic HCV infection, even if their functional role needs to
      be further clarified.

PMID- 9589607
TI  - Estimation of the viability of Vibrio cholerae 0139 by assessing cell membrane
      integrity.
AB  - Changes in the viability of Vibrio cholerae 0139 Bengal, estimated by cellular
      membrane integrity, in batch culture over 35 days, were investigated. Data
      indicated an initial period of rapid growth with up to 30% of bacterial
      mortality, followed by a period of slower growth, lower culturability but higher
      viability, from day 7 onwards. The size of viable bacteria significantly
      decreased during the incubation time, whilst the size of dead bacteria showed a
      less pronounced decrease. V. cholerae 0139 changed from a straight or curved rod
      shape to a spherical shape. This study shows that BacLight dyes are a fast and
      useful tool to examine health risk-associated bacteria, providing useful
      information about their viability and concentration.

PMID- 9589608
TI  - Effect of haemin on the enterotoxin production of Campylobacter jejuni.
AB  - When Campylobacter jejuni was exposed to iron compounds, alterations in
      enterotoxin production were monitored by enzyme linked immunosorbent assay
      (ELISA) and Western blotting. By ELISA, treatment with 10 microM haemin increased
      the ganglioside binding activity of the toxin in the extracellular fraction but
      not in the intracellular fraction. By Western blotting, a 68 kD subunit of the
      enterotoxin was observed to increase in concentration. The results suggest that
      haemin may have a positive regulation effect on enterotoxin maturation when
      released from bacterial cells.

PMID- 9589609
TI  - Exogenous isolation of Hgr plasmids from coastal Mediterranean waters and their
      effect on growth and survival of Escherichia coli in sea water.
AB  - Four self-conjugative plasmids conferring mercury resistance were exogenously
      isolated from coastal Mediterranean sea water. All the plasmids isolated (93.2,
      73.1, 65.2 and 221 kb) showed narrow-spectrum mercury resistance, and no UV
      resistance; three of them conferred cadmium resistance (Cdr 1.5 mM) and two of
      them encoded streptomycin resistance (50 micrograms/ml). Their influence on the
      survival of the recipient strain Escherichia coli JGL1 in different seawater
      media was studied and compared with that of two plasmids previously isolated by
      the same procedure from an epilithic community of the Bristol Channel, Great
      Britain. A significant negative influence was observed for the largest (221 kb)
      of the plasmids isolated and one of the epilithic plasmids (239 kb). The effect
      of the plasmids on E.coli JGL1 was dependent on the seawater media.

PMID- 9589610
TI  - Release of interleukin-2 induced by a major antigenic outer membrane protein of
      Shigella dysenteriae type 1 in natural infection.
AB  - An antigen specific modulation of peripheral blood lymphocyte function was
      examined in a patient-based study of Shigella dysenteriae type 1 infection.
      Interleukin-2 (IL-2) production by the peripheral blood mononuclear cells (PBMC)
      from Shigella-infected patients was correlated with the expression of host
      cellular immune responses. To evaluate the role of a 57 kD major antigenic outer
      membrane protein of S. dysenteriae 1 in the proliferation of PBMC and the
      production of IL-2, the in vitro blastogenic transformation assay was employed.
      The magnitude of the response was monitored morphologically as well as by the
      proliferation of the IL-2 dependent CTLL-2 cell line. The proliferation of the IL
      2 dependent CTLL-2 cell line against PBMC culture fluids after exposure to the
      major antigen reflected the participation of functionally active T-lymphocytes in
      shigellosis patients. The precise quantitation of IL-2 concentration in such
      lymphocyte culture supernatants by immunoassay showed substantial production of
      IL-2.

PMID- 9589611
TI  - Capability of neurite regeneration of rat retinal explant at different ages.
AB  - Neurite regeneration from central nervous tissue of mammalian has been
      demonstrated to occur in early postnatal stage but not in adult stage. To answer
      when the retinal explant of rat loses the neurite regeneration in vitro after
      birth, we have used tissue culture to study the neurite regeneration of retinal
      explant of Wistar rat at different ages. The retinal explants from rat at first
      postnatal day, 3rd postnatal day, one week, two weeks, three weeks, four weeks
      old and of the adult were put in tissue culture to observe the neurite growth
      after four-day incubation. The neurites were also identified by immunochemical
      staining using monoclonal antibody to neurofilament. The capability of neurite
      regeneration of retinal explant was decreased with the passage of time after
      birth, and it was lost after two weeks old. The age of losing retinal
      regenerative capability coincides with that of eye opening and retinal maturation
      of Wistar rat (15th-18th postnatal day, mean 16.2 +/- 1.3 days). These results
      indicate that when the development of retina has been completed, it will lose the
      capability of regeneration in vitro.

PMID- 9589612
TI  - Molecular characterization of Chinese G6PD deficiency by using polymerase chain
      reaction/single strand conformation polymorphism.
AB  - Using the polymerase chain reaction/single strand conformation polymorphism
      (PCR/SSCP), we studied the molecular characterization of 97 (86 male and 11
      female) glucose-6-phosphate dehydrogenase (G6PD) deficient Chinese newborn babies
      and infants in southern Taiwan. Movement shifts were clearly seen in exon 2, 5, 6
      and 12, respectively. No movement shift was seen in exon 9. Mutation
      confirmations were followed by direct sequencing. Using this approach we
      identified the molecular defect in 90 of the 97 above samples. Our results show a
      total of seven variants, the most common being at nucleotide (nt) 1376 mutation G
      ->T 42.3% (41/97) and at nt 1388 mutation G-->A 34.0% (33/97). The other mutation
      sites were at nucleotide 95 A--G (5.2%), nucleotide 392 G-->T (4.1%), nucleotide
      493 A-->G (3.1%) and two new variants with mutation at nucleotide 371 A-->G
      (2.1%) and nucleotide 519 C-->G (2.1%). Still 7.2% (7/97) remained unidentified.
      There was no significant difference in G6PD activity among the different
      mutations. Simple and fast, PCR/SSCP may be suitable for molecular screening for
      G6PD deficiency in Chinese and other people.

PMID- 9589613
TI  - Cranial computed tomography in ischemic stroke patients with and without dementia
      -a prospective study.
AB  - Stroke patients were assessed by brain CT scan, accompanied by demographic and
      clinical factors to predict the development of dementia following an ischemic
      episode. Vascular dementia was defined by NINDS-AIREN criteria. From 50 demented
      and 50 non-demented stroke patients, we analyzed the location of lesion, counted
      the numbers of lacunae, and semiquantitatively assessed the size of infarction,
      severity of overall white matter lesions (WML), and degree of brain atrophy.
      Compared to the non-demented patients, the demented patients: 1) encountered more
      stroke episodes (p < 0.001); 2) had more lacunae at bilateral basal ganglion (p <
      0.001) or thalamus (p < 0.01); and 3) tended to have lesions in left cortex (p <
      0.001), particularly a large infarct at the parietal (p < 0.001) or temporal lobe
      (p < 0.001). Periventricular changes (p < 0.001), subcortical WML (p < 0.001),
      overall WML (p < 0.001), and brain atrophy (p < 0.05) were also more severe in
      the demented group. However, no difference existed in demographic factors between
      the two groups. We concluded that several factors were important in developing
      dementia following an ischemic stroke, and the order by logistic regression would
      be: the severity of overall WML, left parietal infarct, and numbers of thalamic
      lacunae.

PMID- 9589614
TI  - Clinical results of anterior cervical discectomy without interbody fusion.
AB  - A retrospective review of 42 patients who had undergone anterior cervical
      discectomy without bone fusion using an operating microscope was performed to
      analyze the results in patients who had a diagnosis of soft disc herniation or
      spondylosis between 1988 and 1994. There were 29 males and 13 females (age range,
      30 to 77 years). Discectomy of single level was performed in 28 cases and at two
      levels in 14 cases. A soft disc lesion was found in 15 patients and a hard disc
      in 27 patients. A good result was achieved in 93% of patients with soft disc and
      59% of those with hard disc lesion. Twenty-six patients underwent radiological
      evaluation after the surgical intervention. Collapse of disc space was observed
      in 43% of these and vertebral fusion in 28% of these. In analysis of the
      influencing factors, it can be seen the pattern of the onset of symptoms
      significantly influences the surgical result. A comparison of our results at
      follow-up with published series in which the anterior cervical discectomy without
      bone fusion was used, shows no significant differences. Therefore, we recommend
      the anterior discectomy without fusion as the treatment of choice for soft disc
      lesion.

PMID- 9589615
TI  - Modified Blair method for ankle arthrodesis.
AB  - In this study, the ordinary Blair's ankle arthrodesis was modified by
      longitudinal oblique cutting to get the sliding bone graft, up side down
      grafting, and additional screw fixation at talar site with or without staples
      fixation of tibia-talar junction. The method of ankle arthrodesis was used on 34
      cases from 1987 to 1990 with a 91.2% fusion rate and an average 5.6 months fusion
      time. The oblique cut bone graft provided larger contact surface to enhance bony
      fusion and the upside-down bone graft provided stronger tibia-talar bone bridge
      with thicker cortex for distal screw fixation and the distal screw fixation of
      bone graft to talus had the advantage of securing union and maintaining position.
      With such modifications, solid ankle arthrodesis could be obtained even without
      interarticular compression.

PMID- 9589616
TI  - Risk factors of non-arteritic anterior ischemic optic neuropathy (NAION): ocular
      or systemic.
AB  - We retrospectively analyzed 22 patients with non-arteritic anterior ischemic
      optic neuropathy (NAION) seen at Chung-Ho memorial hospital between 1994 and 1996
      to investigate the risk factors of NAION. The risk factors were divided into two
      groups: ocular and systemic. The ocular factors include refractive state,
      intraocular pressure, and cup-disk ratio of fellow eye. The systemic factors
      include diabetes, hypertension and cardiovascular diseases. The analysis
      revealed: (1) only 22.6% of patients with NAION have systemic risk factors; (2)
      intraocular pressure is not specific to NAION; (3) most of fellow eyes (72.6%)
      have cup-disk ratio not more than 0.1; and (4) most patients (90.9%) are
      hyperopic or emmetropic, only 9% of patients are myopic in either affected or
      fellow eyes. The statistical comparison between ocular (including cup-disk ratio
      and refractive state) and systemic factors is significant. The correlation with
      systemic factors in our study was not so high as previous study had reported. On
      the contrary, crowding effect of small cup-disk ratio, which induces a vicious
      circle of generally circulatory compromised disk, may play an important role in
      NAION. Besides, hyperopic or at least emmetropic eyes are more prone to NAION
      than myopic eyes. This may be due to lack of flattening of the temporal
      excavation, therefore adding a predisposing factor to a generally circulatory
      compromised disk. The risk factors associated with NAION seem more strongly
      correlated with ocular factors than with systemic factors.

PMID- 9589617
TI  - The predictors of long-term care service utilization among older Americans.
AB  - Long-term care for the elderly has recently become an area of great interest for
      practicing social workers because of the increasing number of aged persons and
      the important role of government in financing and regulating their care.
      Therefore, the purpose of this study was to provide a set of estimates on
      patterns in long-term care service use among older Americans over an eight-year
      period. This study applied multinomial logistic regression to analyzing the data
      from the National Long-Term Care Survey of 1982-1989 (NLTCS). The results of this
      study showed a number of differences from the results with cross-sectional
      studies. Of the 6,393 sample persons, more than half (56.5%) died over the eight
      years from 1982 to 1989. The rate of entering nursing homes (12.6%) was low. The
      rate of using community-based care services was fairly low. About 10.4 percent of
      the sample received care from helping professional personnel or paid helpers. As
      expected, the number receiving care from kin and other informal support was high.
      Long-term care services in the United States were distributed very unequally
      among various social groups. The indicator of need was not the only determinant
      of service utilization. Other variables such as number of household members,
      race, age and education were also important for service utilization. The
      predictors of deceased versus informal help were need, age, number of household
      member, gender and marital status. The predictors of nursing home care versus
      informal help were need, age, number of household members, education, attitude
      toward nursing home and race. The predictors of community-based help care versus
      informal help were need, number of household members, and education.

PMID- 9589618
TI  - Daily life stress and its correlates among high school students in Hualien city.
AB  - Adolescence is a period of physical, cognitive, social and psychosexual changes.
      These developmental tasks make adolescents particularly vulnerable to life
      stress. The purpose of this study was to assess high school students' perception
      of stress from daily events and to identify its associated factors. A total of
      1,195 high school students were selected via stratified cluster sampling method
      from nine high schools. Data from 1,141 valid answers were analyzed. A self
      administrated questionnaire was used to assess students' demographic
      characteristics, personal traits (self-acceptance, neurotic trait), social
      support and perceived daily life stress. From principal component analysis,
      school work, concern with prospects, parent-teen relationship and peer
      relationship were found to be the main sources of daily life stress perceived.
      Personalities with high neurotic trait or low self-acceptance, perceived low
      social support, Chinese Hans and study at regular high school were important
      related factors. Screening by personality trait and social support questionnaire
      is suggested to be a routine at school to find out the high risk individuals and
      give them assistance in coping with stress.

PMID- 9589619
TI  - Familial intracranial aneurysms.
AB  - We describe a 53-year-old mother and a her 34-year-old son who suffered from
      spontaneous subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage due to
      a ruptured intracranial aneurysm. Diagnosis of the intracranial aneurysm was made
      by CT scan of the brain, and cerebral angiography. These two cases received
      surgical intervention and returned to their previous social activity after
      discharge, even though the mother had arrived in a comatose condition. The
      literature is reviewed and the characteristic expressions of familial
      intracranial aneurysms are described. The etiology of cerebral aneurysms is still
      uncertain but it is likely multifactorial. For the 176 patients with intracranial
      aneurysm(s) treated at Kaohsiung Medical College Hospital, the mean age at
      diagnosis was 51.9 years and these aneurysms were distributed mainly at the
      internal carotid artery (43.8%) and the anterior communicating artery (33.5%).
      The familial aneurysms tend to rupture at a younger age, occur less often at the
      anterior communicating artery and more often at the internal carotid artery and
      the middle cerebral artery as compared with that of non-familial aneurysms. In
      siblings, aneurysms occur at identical sites or at mirror sites and rupture
      within the same decade of life twice as frequently as expected in non-familial
      aneurysm cases. The familial aggregation of intracranial aneurysms and the above
      characteristic expressions suggest that heredity may play a role in some familial
      aneurysms. The pattern of inheritance, however, has not been established.
      Screening examinations and the treatment of unruptured intracranial aneurysms in
      asymptomatic relatives of the familial cases are also discussed.

PMID- 9589620
TI  - Prostatic carcinoma with brain metastasis presenting as a tumor hemorrhage.
AB  - Adenocarcinoma of the prostate commonly metastasizes to the lymph nodes and
      bones, with occasional visceral deposits, however, metastasis to the brain is
      rare. A case of prostatic carcinoma with brain metastasis presenting as a tumor
      hemorrhage is reported. The pertinent literature is also reviewed.

PMID- 9589621
TI  - A multi-level analysis of cultural experience and gender influences on causal
      attributions to perceived performance in mathematics.
AB  - BACKGROUND: Causal attributions to academic performance are among the most
      important factors that influence the student's subsequent achievement behaviour.
      AIM: The effects of student's gender and cultural experience (region) on the
      ratings of previously identified causal attribution factors were investigated.
      SAMPLE: The participants were 341 high school students from the urban (N = 144)
      and the rural (N = 197) regions of Kenya. There were 205 male and 136 female
      students. METHODS: Causal comparative research design was used and data collected
      using the Causal Attribution Scale (CAS). The Hierarchical linear model (HLM)
      technique was used to test the hypotheses. RESULTS: There were significant gender
      and cultural experience variations in the mean ratings of the attribution
      factors. Instructional Strategy was highly rated for perceived success, and lack
      of Ability for perceived failure. Effort was of least importance in making
      attribution to either perceived success or failure. CONCLUSIONS: The findings do
      not concur with research findings from Western and Asian countries where Effort
      is considered important in making attributions for either perceived success or
      failure. The findings, however, agree with research findings from Asian and other
      non-Caucasian societies where success is attributed to external factors (e.g.,
      task difficulty) and failure to internal factors (e.g., ability). These findings
      have some implications for cross-cultural research in causal attribution as it
      relates to academic performance. While certain causal attributions studied in
      'Western' and Asian cultures differ in terms of perceived success and failure,
      the current study indicates that other causal attributions are important and used
      differently by students from Kenya.

PMID- 9589622
TI  - The prevalence and correlates of specific learning difficulties in a
      representative sample of children with hemiplegia.
AB  - BACKGROUND: Children with hemiplegia have cerebral palsy affecting one side of
      the body due to damage to the opposite side of the brain. An investigation of the
      association between hemiplegia and specific learning difficulties (SpLD) provides
      a unique window on body-mind links and left brain/right brain differences. AIMS:
      The present study investigated the prevalence and correlates of SpLDs in children
      with hemiplegia. SAMPLE: A representative sample of 149 London children with
      hemiplegia aged between 6 and 10 included 59 children whose cognitive abilities
      and predicted academic ability were within the average range. METHODS: SpLDs were
      defined by ability-achievement discrepancy analysis. Differences between children
      with and without SpLDs were explored with a between-groups design. RESULTS:
      Children with hemiplegia had significantly more SpLDs than expected, with 36 per
      cent of these children having at least one SpLD. Children with and without SpLDs
      were similar in intelligence and demographic background, but the children with
      SpLDs had significantly more severe neurological impairments and a significantly
      higher rate of emotional and behavioural difficulties (EBDs) than comparison
      children. CONCLUSIONS: Three typical case studies are described and
      recommendations made for the early identification and remediation of SpLDs in
      children with hemiplegia.

PMID- 9589623
TI  - Utility of relaxation training with children in school settings: a plea for
      realistic goal setting and evaluation.
AB  - BACKGROUND: School-based relaxation training programmes are a popular means of
      helping children with anxiety problems such as headaches and test anxiety. AIMS:
      Our major objective is to evaluate the empirical status of school-based
      relaxation training programmes. CONTENTS: Focusing on progressive muscle
      relaxation training, we show how this adult training procedure has been modified
      for use with children. Several training issues are discussed including the
      questions of live versus recorded instruction and individual versus group
      instruction. We also discuss the evaluation of relaxation training programmes in
      school settings, highlighting issues of reliability and validity. CONCLUSIONS:
      Our review of studies examining the efficacy of school-based relaxation training
      shows that improvements are usually modest and of dubious clinical or educational
      significance. Consequently we suggest that when relaxation training is used with
      school children treatment goals should be more modest or, that if improvements in
      specific performance areas are sought, then more comprehensive treatment packages
      be developed which can influence the successful performance of children in target
      areas and reduce anxiety to normal levels.

PMID- 9589624
TI  - Secondary school teachers' perception of pupils' undesirable behaviours.
AB  - BACKGROUND: Previous studies provide inconclusive evidence with regard to the
      influence that teacher, pupil and school characteristics have on teachers'
      attitudes towards problem behaviours. AIMS: To investigate the seriousness of
      several behaviours as perceived by secondary school teachers, and the extent to
      which these perceptions are influenced by a number of characteristics. SAMPLE: A
      sample of 605 randomly selected teachers from 16 state secondary schools
      participated in the study. METHODS: A questionnaire survey method was employed:
      RESULTS: Drug abuse, cruelty/bullying and destroying were perceived as the most
      serious behaviours whereas inquisitiveness and whispering were rated as the least
      serious. Significant grade level differences were observed in all but two of the
      49 behaviours, these being masturbation and obscene notes. While smoking and
      heterosexual activity were perceived significantly more serious in Form 1-2 than
      in Form 4-5 pupils, the converse was true for all the remaining forms of
      behaviour. Irrespective of grade level, a number of significant pupil sex and
      teacher sex differences were observed. Whereas cheating, lying, masturbation and
      heterosexual activity were perceived to be significantly more serious in girls
      than in boys, the converse is true for dreaminess, disorderliness, silliness,
      quarrelsomeness, and restlessness. While female teachers perceived masturbation
      and obscene notes significantly more serious than male teachers the opposite is
      true for disorderliness. School selectivity and teaching experience were
      important moderators of the perceived seriousness of problem behaviours.
      CONCLUSIONS: The study provides additional evidence of the importance of certain
      teacher, pupil and school characteristics as moderators of teachers' perception
      of the seriousness of behaviour.

PMID- 9589625
TI  - A Rasch measurement model analysis of the Revised Approaches to Studying
      Inventory.
AB  - BACKGROUND: The Revised Approaches to Studying Inventory (Entwistle & Tait, 1994)
      comprises 38 self-report items designed to measure student approaches to learning
      in a higher education context. The items have been conceptualised and designed
      from five learning orientations, corresponding to five subscales of the
      Inventory: 'a deep approach', 'a surface approach', 'a strategic approach', 'a
      lack of direction' and 'academic self-confidence'. AIMS: The study aims to create
      an interval level scale for the Inventory and analyse its psychometric properties
      using a modern measurement model, the Extended Logistic Model of Rasch (Andrich,
      1988a, 1988b; Rasch, 1980), and investigate the conceptual design of the
      Inventory. SAMPLE: The sample was 346 students (170 females, 176 males, 212 less
      than 23 years and 134 older than 23), studying in first year Faculty of Business,
      at a university in Perth, Western Australia. METHOD: A scale was created for the
      Inventory and analysed for reliability, fit to the model, meaning and validity.
      The Inventory was analysed separately for each of four subgroups (females, males,
      younger and older students) to test the invariance of the scale. The five
      subscales were analysed separately to test the conceptual design and meaning of
      the Inventory. RESULTS: The Inventory has satisfactory psychometric properties,
      when items 20 and 33 are deleted. Easier and harder items need to be added to
      better target the student measures. Its conceptual design from the five learning
      orientations is confirmed. Only 15 items have satisfactory invariance across the
      four subgroups. The psychometric properties of three subscales (deep approach,
      surface approach and strategic approach) are only moderately satisfactory and the
      item separabilities of the other two (lack of direction and academic self
      confidence) are unsatisfactory. CONCLUSIONS: The Extended Logistic Model of Rasch
      was found to be useful in creating an interval level scale for the Inventory, and
      for analysing its psychometric properties and conceptual design. It is suggested
      that the Inventory can be improved conceptually by adding more items relating to
      attitudes, intentions and behaviour and by adding harder and easier items to
      target the student measures better.

PMID- 9589627
TI  - Interaction of insecticides, entomopathogenic nematodes, and larvae of the
      western corn rootworm (Coleoptera: Chrysomelidae).
AB  - Chemical insecticides and entomopathogenic nematodes have been independently used
      to suppress corn rootworm damage in maize. We report on the mortality response of
      larvae of the western corn rootworm, Diabrotica virgifera virgifera LeConte, to
      the combined treatment with 1 of 3 insecticides (terbufos, fonofos, and
      tefluthrin) and the entomopathogenic nematode Steinernema carpocapsae Weiser
      (Mexican strain). Corn rootworm mortality with combinations of the insecticides
      terbufos or fonofos and S. carpocapsae was typically additive for the 2 agents.
      Evidence of antagonism between these agents was sometimes observed. The
      combination of tefluthrin with S. carpocapsae frequently resulted in a
      synergistic response and a 24% average increase in expected mortality. The
      influence of the tefluthrin appears to be isolated to an effect on the rootworm
      larvae. Synergism also was observed when tefluthrin was combined with the
      nematode Heterorhabditis bacteriophora Poinar (Lewiston strain). The combined use
      of tefluthrin with an entomopathogenic nematode may offer an integrated approach
      to increase the efficacy of entomopathogenic nematodes for insect control.

PMID- 9589628
TI  - Virulence of entomopathogenic nematodes to the western masked chafer Cyclocephala
      hirta (Coleoptera: Scarabaeidae).
AB  - Predictability is a key challenge in biological control of white grubs with
      entomopathogenic nematodes. Most field test failures have been attributed to the
      use of inappropriate nematode strains. We evaluated several species and strains
      of entomopathogenic nematodes (Heterorhabditidae and Steinernematidae) against
      chafer Cyclocephala hirta in a soil and pot bioassay at 25 degrees C. The NJ65
      strain of Steinernema glaseri, isolated from New Jersey, outperformed all other
      steinernematid and heterorhabditid nematodes, resulting in a 76.5% larval
      mortality within 3 d of treatment at 125 nematodes per larva. After 6 days of
      treatment, 4 strains of S. glaseri (NJ21, NJ29, NJ42, and NJ65) achieved 100%
      larval mortality. Other strains that caused > 80% larval mortality after 6 d of
      treatment included NJ32, NJ40, and NJ41 of S. glaseri, and Chino Hill, Merced,
      and Nebraska strains of Heterorhabditis sp. Steinernema anomali (Ryazan),
      Steinernema kushidai (Hamakita), Heterorhabditis megidis (HO1), and H.
      bacteriophora (HP88) caused only 45, 55, 60, and 66.7% larval mortality,
      respectively. Steinernema feltiae (Argentina strain) caused only 16% larval
      mortality, and Steinernema carpocapsae (All and Mexican strains) and Steinernema
      scapterisci (Colon strain) were nonpathogenic to C. hirta. Steinernema riobravis
      caused no larval mortality at 25 degrees C, but inflicted 45-71% mortality at 30
      degrees C. Our studies indicate that S. glaseri and Heterorhabditis spp. are most
      virulent among entomopathogenic nematodes toward C. hirta larvae and certain
      strains of S. glaseri are superior to Heterorhabditis spp.

PMID- 9589629
TI  - Control experiments with yellow jacket wasps (Hymenoptera: Vespidae) injuring
      cattle in Israel.
AB  - Injuries caused by the German yellow jacket Vespula germanica F. to dry and
      lactating dairy cows (Bos tourus) in 5 herds in Israel were monitored and
      adversely affected < or = 65% of the cows. Elimination of large alternative
      protein sources (placentas, sewage containing milk from the milking parlor), and
      prebaiting with high-quality minced meat (or fish) in adequate numbers of baiting
      cages around the dairy farm for several days, are necessary for successful
      control. Significant control was achieved after a shorter period of time when the
      dairy farm was surrounded by a smaller area of uncultivated land than by a larger
      area. At some dairy farms there were significant differences among numbers of
      wasps visiting the various cage sites and significant variability between baiting
      days. Efficient and significant control was achieved by minced meat bait
      containing 1.5% acephate (orthene) and 2% microencapsulated diazinon (Antikan).
      Wasps were totally repelled by minced meat bait containing 2.25% of a plant
      derived bioinsecticide derived from Meliaceae (Ag1000). The potential of using Ag
      1000 for repelling yellow jackets from teats and udders of dairy cows is
      discussed.

PMID- 9589630
TI  - Clinical review 94: What's in a name? In search of leptin's physiologic role.

PMID- 9589631
TI  - Growth in bone mass and size--are racial and gender differences in bone mineral
      density more apparent than real?

PMID- 9589632
TI  - Differential effect of race on the axial and appendicular skeletons of children.
AB  - The prevalence of osteoporosis and the incidence of fractures are substantially
      lower in black than in white subjects, a finding generally attributed to racial
      differences in adult bone mass. Whether these racial differences are present in
      childhood is the subject of considerable interest, as the amount of bone gained
      during growth is a major determinant of future susceptibility to fractures. We
      measured the density and size of the vertebrae and femurs of 80 black and 80
      white healthy children, 8-18 yr of age, matched for age, gender, height, weight,
      and stage of sexual development, using computed tomography. Race had a
      significant and differential effect on the bones in the axial and appendicular
      skeletons. In the axial skeleton, black children had greater cancellous bone
      density, but similar cross-sectional area of the vertebral bodies. In contrast,
      in the appendicular skeleton, black children had greater femoral cross-sectional
      area, but similar cortical bone area and cortical bone density. Compared to white
      children, vertebral bone density and femoral cross-sectional area at sexual
      maturity were, on the average, 10.75% and 5.7% higher, respectively, in black
      children. Such significant variations may contribute to the racial differences in
      the prevalence of osteoporosis between black and white adults.

PMID- 9589633
TI  - Where you go depends on where you are. Early investigations on the use of
      deoxycorticosterone in Addison's disease: a historical vignette.

PMID- 9589634
TI  - Severe congenital hyperthyroidism caused by a germ-line neo mutation in the
      extracellular portion of the thyrotropin receptor.
AB  - Gain of function mutations in the TSH receptor (TSHR) have been identified as the
      molecular basis for congenital and acquired forms of autonomous thyroid function.
      Herein, we report the molecular characterization of a case of severe congenital
      hyperthyroidism with a history of hyperthyroidism in the paternal aunt and the
      paternal grandmother, who were both found to be heterozygous for a mutation
      (R528H) located in exon 10 of the TSHR gene. Functional expression of the mutant
      TSHR-R528H in COS-7 cells, however, did not result in constitutive activity of
      the TSHR. Subsequent analysis of exons 1-9 led to the detection of an additional
      heterozygous mutation (S281N) in the patient, but not in other family members.
      Interestingly, the latter mutation is located in the extracellular domain of the
      TSHR, and functional studies revealed a marked increase in basal cAMP levels when
      the mutant receptor was expressed in COS-7 cells. To address the question of
      whether both mutations were present on the same allele, a double mutant TSHR
      (S281N/R528H) was generated and characterized. These functional studies in
      conjunction with RT-PCR analysis of thyroid tissue obtained from subtotal
      thyroidectomy performed at the age of 6 yr revealed that the patient bears two
      distinct mutations on different alleles: the familial paternal R528H mutation to
      be regarded as a polymorphism and a de novo mutation (S281N) on the maternal
      allele accounting for the clinical picture. Thus, the main conclusions to be
      drawn from this case are 1) a search for mutations in cases of congenital
      nonautoimmune hyperthyroidism should not remain restricted to exon 10 of the TSHR
      gene, because germ-line gain of function mutations of the TSH receptor can be
      located outside of the transmembrane core of the receptor; and 2) this case
      illustrates the necessity for careful functional characterization of any novel
      mutation before a causal relationship to hyperthyroidism can be established.

PMID- 9589635
TI  - Definitive adrenal insufficiency due to bilateral adrenal hemorrhage and primary
      antiphospholipid syndrome.

PMID- 9589636
TI  - Alterations in growth and body composition during puberty: III. Influence of
      maturation, gender, body composition, fat distribution, aerobic fitness, and
      energy expenditure on nocturnal growth hormone release.
AB  - We examined the relationships among gender, sexual maturation, four-compartment
      model estimates of body composition, body fat distribution (magnetic resonance
      imaging for abdominal visceral fat and anthropometrics), aerobic fitness, basal
      and total energy expenditure, and overnight GH release in an ultrasensitive
      chemiluminescence assay in healthy prepubertal and pubertal boys (n = 18 and 11,
      respectively) and girls (n = 12 and 18, respectively). Blood samples were
      withdrawn every 10 min from 1800-0600 h to determine the area under the serum GH
      time curve (AUC), sum of the GH peak heights (sigma GH peak heights), and the
      mean nadir GH concentration. GH release was greater in the pubertal than
      prepubertal subjects due to an increase in sigma GH peak heights (43.8 +/- 3.6
      vs. 24.1 +/- 3.5 ng.mL-1, P = 0.0002) and mean nadir (1.7 +/- 0.2 vs. 0.7 +/- 0.2
      ng.mL-1, P = 0.0002), but not peak number (4.3 +/- 0.2 vs. 4.5 +/- 0.2). The
      girls had a greater sigma GH peak heights (39.0 +/- 3.5 vs. 28.8 +/- 3.6 ng.mL-1,
      P = 0.05) and mean nadir concentration (1.4 +/- 0.2 vs. 0.9 +/- 0.2 ng.mL-1, P =
      0.05) than the boys. Significant inverse relationships existed between sigma GH
      peak heights (r = -0.35, P = 0.06) or mean nadir (r = -0.39, P = 0.04) and four
      compartment percent body fat for all boys but not for all girls or when combining
      all subjects. For all girls, significant inverse relationships existed between
      sigma GH peak heights (r = -0.39, P = 0.03) or mean nadir (r = -0.37, P = 0.04)
      and waist/hip ratio. Similar inverse relationships in all boys or all subjects
      were not significant. Forward stepwise regression analysis determined that bone
      age (i.e. maturation, primary factor) and gender were the significant predictors
      of AUC, sigma GH peak heights, and mean nadir. The influence of maturation
      reflects rising sex steroid concentrations, and the gender differences appear to
      be because of differences in estradiol concentrations rather than to body
      composition or body fat distribution.

PMID- 9589637
TI  - Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited
      albumin defect.
AB  - We report the abnormal albumin in members of a Thai family that presented with
      high serum total T3 but not T4 when measured by radioimmunoassay. In contrast,
      total T3 values were very low when measured by ELISA and chemiluminescence. The
      subjects have no goiter, and clinically euthyroid. Their serum free T4, free T3,
      and TSH were normal. Spiking of T3 to affected serum showed good recovery by
      radioimmunoassay, but very poor recovery by ELISA and by chemiluminescence. The
      immunoprecipitation with labeled T3 bound to albumin showed high percent
      precipitation in affected serum. T3-binding studies showed that the association
      constant of serum albumin in affected subjects was 1.5 x 10(6) M-1 or 40-fold
      that of unaffected relatives of 3.9 x 10(4) M-1. In contrast, the Ka of HSA for
      T4 in an affected subject was only 1.5-fold that of a normal. Albumin
      complementary DNA from leukocytes of affected member was amplified and sequenced.
      We found the second nucleotide of normal codon 66 (CTT), a thymine, was
      substituted by a cytosine (CCT), resulting in the replacement of the normal
      leucine by proline. This is the first report of variant albumin causing familial
      dysalbuminemic hypertriiodothyroninemia.

PMID- 9589638
TI  - Neonatal hyperinsulinemic hypoglycemia: heterogeneity of the syndrome and keys
      for differential diagnosis.
AB  - The two major forms of infantile persistent hyperinsulinemic hypoglycemia require
      different treatments, but are difficult to differentiate during surgery. Indeed,
      one is characterized by focal adenomatous hyperplasia often macroscopically
      invisible, whereas the other consists of a diffuse, but discreet, beta-cell
      abnormality. We evaluated, in a large series of persistent hyperinsulinemic
      hypoglycemia, the reliability of two criteria in differentiating these two forms:
      the mean beta-cell nuclear radius (MNR) and the beta-cell nuclear crowding, i.e.
      the number of nuclei per 1000 micron 2 beta-cell (BCNC). The values of the
      largest MNR and of BCNC in cases bearing a focal lesion (respectively, 3.27
      microns +/- 0.25 and 14.62 +/- 1.78) were significantly different from those in
      the diffuse pathology (4.25 microns +/- 0.43 and 10.00 +/- 1.55). Setting the
      threshold value of MNR at 3.70 microns and that of BCNC at 12.00 enabled correct
      classification of 90.9% of the diffuse and 100% of the focal forms. beta-Cell
      nuclear analysis can thus contribute to a subclassification of the syndrome, not
      allowed by clinical or biological data. If performed during surgery it could help
      in determining the extent of pancreatectomy necessary to cure the patient, as the
      diffuse form, with abnormal nuclei in the whole pancreas, requires subtotal to
      near-total pancreatectomy, whereas the focal form, devoid of abnormal insular
      beta-cell nuclei, can be cured by partial pancreatectomy.

PMID- 9589639
TI  - Near normalization of final height with adapted doses of growth hormone in
      Turner's syndrome.
AB  - An adapted GH dose regimen was evaluated in 14 untreated patients with Turner's
      syndrome. The initial GH dose (0.7 U/kg.BW) was increased by 0.7 U/kg.BW, up to a
      maximum of 2.1 U/kg.BW, when growth velocity (GV) declined to less than 200% of
      the pretreatment level. These patients were compared to a group of 17 patients
      with similar initial characteristics, who received a fixed dose of 0.9 U/kg.BW
      GH. Tolerance to both GH regimens was excellent. The adapted GH doses only
      partially prevented the waning effect observed with conventional doses of GH, and
      the initial goal of doubling GV was only achieved in 42% of the 112 patient
      semesters. Doubling the GH dose from 0.7 to 1.4 U/kg.BW increased the GV by 1.6
      +/- 1.8 cm/yr (P < 0.006); increasing the GH dose from 1.4 to 2.1 U/kg.BW
      increased GV by 0.8 +/- 1.3 cm/yr (P = NS). The overall height gain during the 4
      yr trial was 25.6 +/- 3.9 cm in the adapted dose group and 21.8 +/- 3.9 cm in the
      conventional group (P < 0.02). Final height (FH) results were obtained in 12 of
      14 patients in the adapted dose group and all 17 patients in the conventional
      group and compared to the predicted FH using Lyon's method. The estimated height
      benefit was 10.6 +/- 3.8 cm in the adapted dose group compared to 5.2 +/- 3.7 cm
      in the conventional group (P < 0.01). Eighty-three percent of the patients in the
      adapted dose group had an FH superior or equal to -2 SD score for the general
      population compared to 29% in the conventional group. In conclusion, a marked
      increment in the GH dose in girls with Turner's syndrome associated with a
      relatively late age at introduction of estrogen therapy brought 83% of the
      patients into the lower range of the normal height distribution of the general
      population.

PMID- 9589640
TI  - The metabolic syndrome and insulin-like growth factor I regulation in adolescent
      obesity.
AB  - Although low GH levels are commonly seen in obese adults and children, the
      effects of obesity on the insulin-like growth factor (IGF)/IGF-binding protein
      (IGFBP) system have not been established. As GH and IGF-I normally increase
      during adolescence, we investigated the effects of obesity on circulating total
      and free IGF-I levels and IGFBP-1, -2, and -3 in 19 obese adolescents [14 +/- 1
      yr old; body mass index (BMI), 34 +/- 3], 20 lean adolescents (14 +/- 1 yr old;
      BMI, 23 +/- 0.5), and 10 lean adults (22 +/- 0.7 yr; BMI, 22 +/- 0.7). Fasting
      plasma insulin levels were significantly greater in obese adolescents than in
      either lean group, whereas circulating IGFBP-1 levels were suppressed in an
      inverse relationship to basal insulin (r = -0.49; P < 0.01). Low IGFBP-1 levels
      were associated with normal to increased free IGF-I levels in obese adolescents,
      even though total IGF-I values were lower than those in lean adolescents. Basal
      GH and IGFBP-3 levels were also lower in obese vs. lean adolescents. Basal IGFBP
      1 levels were markedly reduced in obese adolescents (14 +/- 3 ng/mL) vs. those in
      adolescents and adults. No further suppression of IGFBP-1 levels was observed in
      the obese group during a two-step 8 and 40 mU/m2 insulin clamp. In contrast,
      IGFBP-1 levels were promptly lowered in lean adults. Basal IGFBP-2 levels were
      significantly lower in both groups of adolescents vs. lean adults (P < 0.05), and
      IGFBP-2 levels did not change during euglycemic hyperinsulinemia. These data
      suggest that the compensatory hyperinsulinemia that characterizes adolescent
      obesity chronically suppresses levels of IGFBP-1, and low IGFBP-1 concentrations
      may serve to increase the bioavailability of free IGF-I, which may, in turn,
      contribute to lower circulating GH, total IGF-I, and IGFBP-3 concentrations.

PMID- 9589641
TI  - Assessment of Turner's syndrome by molecular analysis of the X chromosome in
      growth-retarded girls.
AB  - Turner's syndrome (TS) is a common disorder (1/2500 to 1/5000 female births)
      which is diagnosed at birth in approximately 20% of patients and during childhood
      or at puberty for the rest. Growth retardation is the most frequent clinical
      feature of TS, so we systematically searched for TS in female patients referred
      to our center because of short stature. Three hundred seventy-five female
      patients, 1 month to 18 yr old (mean +/- SD = 9(7/12) +/- 3(9/12), with growth
      retardation (less than -2 SD) and/or decreased height velocity were included in
      the study. Mean growth retardation was -2.57 SD +/- 0.79 (range: -1 to -7).
      Thirty-two percent of the patients had reached puberty. GH provocative tests were
      performed in 329 patients (87.7%), and 36 of these patients (11%) had impaired GH
      secretion (5 complete and 31 partial GH deficiency). TS was evaluated by Southern
      blot analysis of leukocyte DNA using a multiallelic polymorphic X chromosome
      marker (88% heterozygosity rate). Y chromosome PCR analysis was carried out if a
      pattern indicative of TS was obtained. Leukocyte DNA analysis produced an
      abnormal restriction pattern for 20 of the 375 cases (5.3%). There was a single
      hybridizing band in 13 cases, an allelic disproportion indicative of mosaicism in
      6 cases, and 3 hybridizing bands in 1 case. One patient tested positive in the Y
      chromosome PCR analysis. Cytogenetic analysis showed 47 XXX trisomy in the
      patient with a 3-hybridizing-band pattern and confirmed the diagnosis of TS for
      17 of the 19 suspected cases: 45 X: n = 7; 45 X/46 Xi(Xq): n = 4; 45 X/46 XX: n =
      2; 46 Xi(Xq): n = 1; 45 X/46 Xr(X): n = 1; 45 X/46 XX/47 XXX: n = 1; 45 X/46 XY:
      n = 1. Cytogenetic analysis was normal (46 XX) for the 2 other patients. The TS
      phenotype is variable: dysmorphism is often missing or mild (particularly in
      cases of mosaicism), but growth is reduced in virtually all patients. Screening
      of 375 growth-retarded girls identified 18 cases of TS, of which 17 were
      diagnosed by molecular analysis. This incidence (4.8%) was significantly higher
      than the expected incidence in this population (0.8-1.6%: P < 0.001).

PMID- 9589642
TI  - Effects of human growth hormone, insulin-like growth factor I, and diet and
      exercise on body composition of obese postmenopausal women.
AB  - To determine the effects of GH and insulin-like growth factor I (IGF-I)
      administration, diet, and exercise on weight loss, body composition, basal
      metabolic rate (BMR), muscle strength, and psychological status, 33 moderately
      obese postmenopausal women (67.1 +/- 5.2 yr) participated in a 12-week
      randomized, double blind study. Participants were placed on a diet that provided
      500 Cal/day less than that needed for weight maintenance, and they walked 3 days
      and strength trained 2 days each week. Subjects also self-injected GH (0.025
      mg/kg BW.day), IGF-I (0.015 mg/kg BW.day), a combination of these doses of GH and
      IGF-I, or placebo (P). Twenty-eight women completed the study, as five subjects
      dropped out due to intolerable side-effects (e.g. edema). Weight loss occurred in
      all groups, with the largest decrease occurring in the GH plus IGF-I group (5.6
      +/- 1.4 kg). Fat mass significantly decreased in all groups, with the largest
      losses observed in GH and GH plus IGF-I groups (6.3 +/- 1.8 and 8.4 +/- 2.8 kg,
      respectively). Despite weight loss, BMR was maintained in all groups. Muscle
      strength increased with training for all groups, and depression and anxiety
      scores decreased in groups receiving IGF-I. These data show that obese
      postmenopausal women can lose weight and fat without compromising fat free mass,
      BMR, or gains in muscle strength, and that GH and IGF-I given together may
      enhance fat loss over either given alone.

PMID- 9589643
TI  - Plasma levels of corticotropin-releasing hormone in the inferior petrosal sinuses
      of healthy volunteers, patients with Cushing's syndrome, and patients with pseudo
      Cushing states.
AB  - The objective of this study was to determine whether measurements of human CRH in
      the inferior petrosal sinuses could distinguish patients with Cushing's syndrome
      from those with pseudo-Cushing states or normal physiology. Twenty-five patients
      with Cushing's disease, 17 patients with the syndrome of ectopic ACTH, 7 patients
      with Cushing's syndrome of adrenal origin, 6 patients with pseudo-Cushing states,
      and 11 volunteers believed to have normal hypothalamic-pituitary-adrenal axes
      were studied. Basal plasma human CRH and ACTH were measured at two time points in
      the petrosal sinuses and in a peripheral vein. Most subjects were studied after
      the administration of intravenous diazepam or midazolam and fentanyl, but because
      of the known inhibitory effects of such sedation on CRH secretion, 2 normal
      volunteers and 3 patients with pseudo-Cushing states were studied without
      sedation. Human CRH levels were near or below the detection limit of the assay in
      all subjects. Although the normal volunteers and patients with pseudo-Cushing
      states who were studied without sedation had significantly greater inferior
      petrosal sinus ACTH levels than those who received sedation, there were no
      differences in measured human CRH levels for any of the groups. We conclude that
      inferior petrosal sinus human CRH levels are not easily measured in the inferior
      petrosal sinuses and cannot be used to determine whether individual patients may
      have hypersecretion of CRH causing their ACTH secretion.

PMID- 9589644
TI  - Circulatory dysfunction in asymptomatic in vitro fertilization patients.
      Relationship with hyperestrogenemia and activity of endogenous vasodilators.
AB  - Severe ovarian hyperstimulation syndrome (OHSS) is consistently associated with a
      circulatory dysfunction characterized by arterial hypotension, low peripheral
      vascular resistance, and increased activity of the renin-aldosterone system. To
      investigate whether circulatory dysfunction also occurs in asymptomatic patients
      undergoing controlled gonadotropin ovarian hyperstimulation under pituitary
      suppression for in vitro fertilization (IVF), 12 women without clinical
      manifestations of OHSS underwent sequential blood, urine, and hemodynamic
      measurements at five study points: the 7th day of the menstrual cycle preceding
      IVF (study point 1 or baseline), the day when pituitary suppression was shown
      (study point 2), the day of hCG ovulatory injection (study point 3), the day
      after hCG was injected (study point 4), and 7 days after hCG administration
      (study point 5). Mean arterial pressure, cardiac output, peripheral vascular
      resistance, plasma concentrations of estradiol (E2) and aldosterone, and plasma
      renin activity (PRA) were measured at each study point in all women. Serum levels
      of nitrite/nitrate, and plasma concentration of atrial natriuretic peptide,
      norepinephrine, adrenomedullin, and cyclic guanosine 3'5'-monophosphate were
      measured in samples obtained at study points 1 and 5. Multiple follicular
      development during ovarian stimulation associated with increased plasma E2
      concentration (mean peak plasma E2 level, 2430 +/- 428 pg/mL, range 1630-3840
      pg/mL) were observed in each woman. All patients developed a significant increase
      in cardiac output and decrease in arterial pressure and peripheral vascular
      resistance, and a marked elevation in PRA and aldosterone, all indicating the
      development of arteriolar vasodilation. Changes in circulatory measurements were
      temporarily related with the increase in E2 both being detected at study points 3
      5. In contrast, there was a clear chronological dissociation between the increase
      in plasma E2 concentration and the stimulation of the renin-aldosterone system.
      PRA and aldosterone only reached abnormal levels at study point 5 in association
      with a significant increase in plasma norepinephrine concentration. Serum levels
      of nitrite/nitrate and plasma concentrations of atrial natriuretic peptide,
      adrenomedullin, and cyclic GMP were similar at study points 1 and 5. It is
      concluded that the circulatory dysfunction that characterizes severe OHSS is a
      universal event in patients undergoing controlled ovarian hyperstimulation for
      IVF. Although the increase in E2 levels during IVF cycles is associated with
      significant circulatory changes, the circulatory dysfunction that characterizes
      severe OHSS is clearly unrelated to the onset of hyperestrogenemia. Arteriolar
      vasodilation during IVF cycles was not associated with an increased activity of
      the vasodilator substances atrial natriuretic peptide, adrenomedullin, and nitric
      oxide.

PMID- 9589645
TI  - Age-related perception of stature, acceptance of therapy, and psychosocial
      functioning in human growth hormone-treated girls with Turner's syndrome.
AB  - This study evaluated the perception of stature, acceptance of therapy, and
      psychosocial functioning in relation to age at onset and time on treatment during
      2 yr of GH therapy in 31 girls with Turner's syndrome grouped by age (group A:
      3.7-5.8 yr, n = 9; group B: 7.2-11.8 yr, n = 13; group C: 12.5-16.4 yr, n = 9).
      The growth response after 2 yr was significant in the 3 groups when calculated in
      terms of growth norms for untreated Turner girls (mean increase in height SD
      score: +1.2, +1.5, and +1.1, respectively). The effect was less marked in terms
      of growth norms for normal girls, particularly in group B (+0.5 SD score). Height
      was perceived as a problem by most patients, except in the youngest girls at the
      start of treatment (group A) and in the majority of the adolescents after 2 yr of
      GH therapy (group C), without evidence of relation to growth response during
      therapy. The GH injections were fairly well accepted by all patients, except
      those younger than 6 yr. In all patients, expected adult height was unrealistic
      and became more realistic with age, whereas no consistent changes were observed
      in relation to growth response to GH therapy. The Child Behavior Checklist
      revealed elevated mean scores at the behavioral subscales of attention problems
      (group A and B), social problems, withdrawal, and anxiety-depression (most
      obviously in group B). No significant changes were seen during GH therapy. In
      group C, an elevated mean social problem score at the Youth Self Report and a low
      mean social self-esteem score at the Self-Esteem Inventory were observed before
      therapy and showed a significant improvement during 2 yr of GH treatment. These
      results, however, might be biased due to an increase in social desirability
      during therapy. We conclude that the perception of height, acceptance of GH
      therapy, and psychosocial functioning in girls with Turner's syndrome show
      important differences between age groups, with only slight changes observed
      during GH therapy.

PMID- 9589646
TI  - The relationship between growth hormone kinetics and sarcopenia in postmenopausal
      women: the role of fat mass and leptin.
AB  - Sarcopenia, the decline in body cell mass (BCM) and especially in muscle mass
      with age, is an important age-related cause of frailty and loss of independence
      in the elderly. Because the decline in BCM with age parallels a decline in GH
      secretion from young adulthood to old age, loss of GH secretion has been
      considered an important contributory cause of sarcopenia in the elderly. To test
      this hypothesis in a group of healthy postmenopausal women (n = 15; mean +/- SD
      age, 66.9 +/- 7.8 yr), 24-h GH concentrations and secretory kinetics were
      correlated with BCM (measured by whole body counting of 40K) and percent body fat
      (measured by dual energy x-ray absorptiometry or neutron inelastic scattering).
      Serum leptin levels were determined as a measure of adipocyte mass. Contrary to
      prediction, GH secretion was lower in women with higher BCM (r = 0.50; P < 0.05),
      whereas their mean fat mass was higher (r = 0.51, P < 0.05). These data indicate
      that sarcopenia in postmenopausal women is not associated with reduced GH
      secretion and is inversely correlated with fat mass. Serum leptin levels were
      inversely associated with GH secretion (r = -0.67; P < 0.006). Although a causal
      relationship has not been demonstrated, these data suggest that leptin could
      modulate GH secretion through its action on the aging hypothalamic-pituitary
      axis, or that GH regulates leptin secretion.

PMID- 9589647
TI  - Recombinant human luteinizing hormone (LH) to support recombinant human follicle
      stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient
      anovulatory women: a dose-finding study. The European Recombinant Human LH Study
      Group.
AB  - The efficacy of recombinant human LH (rhLH) for supporting human (rhFSH)-induced
      follicular development was investigated in hypogonadotropic hypogonadal women
      (WHO group I anovulation). Patients (n = 38) were randomized to receive rhLH (0,
      25, 75, or 225 IU/day) in addition to a fixed dose of rhFSH (150 IU/day). rhLH
      was found 1) to promote dose-related increases in estradiol (E2) and
      androstenedione secretion by rhFSH-induced follicles, i.e. serum concentrations
      on the last day of FSH administration were 65 +/- 4, 195 +/- 94, 1392 +/- 585,
      and 2441 +/- 904 pmol/L for E2 and 3.6 +/- 0.9, 5.1 +/- 1.3, 6.4 +/- 1.3, and 6.7
      +/- 1.3 nmol/L for androstenedione for patients treated with 0, 25, 75, and 225
      IU rhLH, respectively; 2) to increase ovarian sensitivity to FSH, as demonstrated
      by the proportion of patients who developed follicles after the administration of
      a fixed dose of FSH, i.e. 1 of 8, 3 of 7, 7 of 9, and 8 of 10 in patients treated
      with 0, 25, 75, and 225 IU rhLH, respectively; and 3) to enhance the ability of
      these follicles to luteinize when exposed to hCG. A daily dose of 75 IU rhLH was
      effective in the majority of women in promoting optimal follicular development
      (defined as > or = 1 follicle > or = 17 mm; E2, > or = 400 pmol/L; midluteal
      phase progesterone, > or = 25 nmol/L) and maximal endometrial growth. A minority
      of patients may require up to 225 IU/day. rhLH, given sc at a dose up to 225
      IU/day, was not immunogenic and was well tolerated.

PMID- 9589648
TI  - Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2
      diabetic patients.
AB  - The objective of this study was to determine the safety, efficacy, and
      tolerability of the alpha-glucosidase inhibitor miglitol vs. the sulfonylurea
      glyburide in the treatment of elderly patients with type 2 diabetes mellitus,
      inadequately controlled by diet alone. This was a double-blind, randomized,
      placebo-controlled, 1-yr trial of miglitol 25 mg TID and 50 mg TID compared with
      placebo and a titrated dose of glyburide in a parallel group comparison study
      conducted in 30 out-patient sites across the United States. Four hundred eleven
      (411) diet-treated patients age 60 yr or greater were randomized to receive
      either placebo TID (n = 101), miglitol 25 mg TID (n = 104), miglitol 50 mg TID (n
      = 102), or a once-daily dose of glyburide titrated based on fasting plasma
      glucose (FPG) (n = 104), for a period of 56 weeks. Efficacy was assessed by
      glycated hemoglobin (HbA1c), fasting and post-meal glucose, insulin, and lipid
      levels, and by 24-h urinary excretion of glucose and albumin. Safety and
      tolerability were assessed by tabulation of adverse events, periodic laboratory
      determinations, and home blood glucose monitoring. HbA1c treatment effects
      (placebo-subtracted change in HbA1c from baseline) at the 1-yr endpoint were 
      0.49%, -0.40%, and -0.92% in the miglitol 25 mg TID, miglitol 50 mg TID, and
      glyburide groups, respectively (P < 0.05- 0.01 vs. placebo). Postprandial insulin
      levels were significantly greater than placebo and miglitol in the glyburide
      group (P < 0.01). Hypoglycemia, weight gain, and both routine and serious
      cardiovascular events were more frequent in the glyburide group (P < 0.05-0.01
      vs. placebo or miglitol groups). Diarrhea (or soft stools) and flatulence were
      more common in both miglitol groups than in the other two groups in a dose
      dependent manner, but resulted in relatively few study dropouts. Treatment with
      miglitol offers the elderly type 2 diabetic patient significant reductions in
      daylong glycemia as measured by HbA1c. The greater HbA1c reductions seen with
      once-a-day glyburide occurred at a cost of significant increases in weight,
      insulin levels, and the incidences of clinical and subclinical hypoglycemia,
      which did not occur in the miglitol groups. alpha-glucosidase inhibitors are a
      useful and relatively safe therapeutic option in the elderly patient with type 2
      diabetes.

PMID- 9589649
TI  - Oscillations in sympatho-vagal balance oppose variations in delta-wave activity
      and the associated renin release.
AB  - To determine the potential role of the sympathetic nervous system in the
      generation of the oscillations in PRA over the 24-h period, we used the
      autocorrelation coefficient of RR interval (rRR), a new tool to evaluate the
      sympatho-vagal balance continuously. We determined the influence of the
      sympathetic nervous system both on the nocturnal PRA oscillations associated to
      increases in delta-wave activity and on the daytime oscillations that occur
      randomly in awake subjects. PRA and rRR were determined every 10 min during 24 h
      in nine healthy subjects under continuous bed rest. Electroencephalographic
      spectral analysis was used to establish the variations in delta-wave activity
      during sleep, from 2300-0700 h. The overnight profiles in PRA, rRR and delta-wave
      activity were analyzed using a modified version of the pulse detection program
      ULTRA. The temporal link among the profiles of rRR, PRA, and delta-wave activity
      was quantified using cross-correlation analysis. During sleep, large oscillations
      in PRA were strongly linked to variations in delta-wave activity. They were
      preceded by opposite oscillations in rRR, decreases in rRR reflecting predominant
      vagal activity, and increases in rRR reflecting sympathetic dominance. During the
      waking periods, the levels of rRR were higher, with smaller variations. The
      daytime PRA oscillations were not associated with any significant changes in rRR,
      and conversely, significant oscillations in rRR were not followed by any
      significant changes in PRA. In conclusion, the sympathetic nervous system is not
      directly involved in the generation of renin oscillations observed under basal
      conditions. During sleep, the oscillations in sympatho-vagal balance are
      inversely related to the variations in delta-wave activity and the associated
      renin release. The processes that give the intermittent signal for concomitant
      increases in slow wave activity and renin release from the kidney remain to be
      identified.

PMID- 9589650
TI  - Energy requirements and physical activity of older free-living African-Americans:
      a doubly labeled water study.
AB  - We examined daily energy requirements and determinants of physical activity in
      older, free-living African-American women (n = 37; age, 64 +/- 8 yr) and men (n =
      28; age, 64 +/- 7 yr). Total daily energy expenditure and its components [i.e.
      resting metabolic rate (RMR) and physical activity energy expenditure] were
      determined using doubly labeled water and indirect calorimetry. Body composition
      from dual energy x-ray absorptiometry, maximal oxygen consumption from a graded
      treadmill test, and leisure time physical activity from a structured interview
      were determined. Total daily energy expenditure adjusted for body composition was
      lower (P < 0.05) for women (2198 +/- 621 kcal/d) than for men (2633 +/- 669
      kcal/d) due to a lower RMR (1431 +/- 240 vs. 1576 +/- 259 kcal/d; P = 0.07) and
      physical activity energy expenditure (548 +/- 559 vs. 794 +/- 603 kcal/d; P =
      0.19), respectively. The physical activity level ratio (i.e. total daily energy
      expenditure/RMR) was not different from Food and Agriculture Organization/World
      Health Organization/United Nations University recommendations (i.e. 1.51) for
      women (1.51 +/- 0.25), but was higher for men (1.71 +/- 0.32). The strongest
      correlates with physical activity energy expenditure were age for women (r = 
      0.44; P < 0.01) and maximal oxygen consumption for men (r = 0.39; P < 0.05).
      These data show that daily energy requirements are significantly lower in African
      American women compared to men, primarily due to lower levels of physical
      activity energy expenditure. Furthermore, lower levels of cardiovascular fitness
      in men and advancing age in women are associated with lower physical activity
      energy expenditure.

PMID- 9589651
TI  - Renal tubular reabsorption of phosphate is positively related to the extent of
      bone metastatic load in patients with prostate cancer.
AB  - Osteolytic metastases are often associated with decreased renal tubular
      reabsorption of phosphate. There is, however, no specific data on phosphate
      metabolism in metastases from prostatic cancer, which are generally osteoblastic.
      The aim of the present study was to investigate renal handling of inorganic
      phosphate (Pi) in prostatic cancer, in patients without or with skeletal
      metastases of various extents. Forty-eight patients were the subjects of this
      study. There were 39 with malignant disease, of whom 27 had bony metastases. Nine
      other patients had benign prostate hyperplasia. Biochemical indexes of prostatic
      tumor, renal tubular reabsorption of calcium and Pi, biochemical markers of bone
      remodeling, and relevant calciotropic hormones were measured and analyzed in
      relation to the extent of skeletal metastases, as assessed by bone scintigraphy.
      A higher bone metastatic load was associated with significantly greater prostate
      specific antigen and prostatic acid phosphatase levels (P < 0.05), increased
      levels of biochemical markers of bone formation (P < 0.05) and resorption (P <
      0.001), higher maximal renal tubular reabsorption of Pi (TmPi/GFR; P < 0.05), and
      higher urinary cAMP excretion (P < 0.05). Nine patients among those with bone
      metastases (n = 27) had higher TmPi/GFR than metastasis-free patients. These had
      a greater value of osteocalcin (P < 0.001). Also, 8 of these had relatively more
      extensive skeletal metastatic load. In patients with prostatic cancer, high
      skeletal metastatic load was accompanied by increased TmPi/GFR despite higher
      urinary cAMP excretion, which is supposed to reduce the TmPi/GFR. These results
      support the hypothesis that renal tubular reabsorption of Pi is capable of
      adaptation to meet demands for minerals in the face of enhanced bone formation.

PMID- 9589652
TI  - Effects of chronic growth hormone treatment on energy intake and resting energy
      metabolism in patients with human immunodeficiency virus-associated wasting--a
      clinical research center study.
AB  - In previous studies, treatment with recombinant human GH (rhGH) produced
      sustained increases in weight and lean body mass (LBM) and decreases in fat mass
      in patients with human immunodeficiency virus (HIV)-associated wasting. To
      evaluate the effects of chronic rhGH treatment on components of energy balance,
      we recruited separate subgroups of HIV-positive patients with an involuntary
      weight loss of 10% or more to undergo paired measurements of resting energy
      metabolism (n = 6) or food intake (n = 11) before and during the final week of a
      3-month rhGH (0.1 mg/kg.day) treatment period. In the energy metabolism subset,
      resting energy expenditure (REE) and substrate oxidation rates were measured by
      indirect calorimetry during brief admissions to a metabolic ward. Patients in the
      energy intake subset prepared written 4-day food intake diaries. Body composition
      was measured in both groups by bioelectrical impedance analysis. Changes in
      weight (+2.2 +/- 0.9 and +2.2 +/- 0.6 kg), LBM (+3.2 +/- 0.6 and +3.8 +/- 0.5
      kg), and fat (-1.0 +/- 0.5 and -1.6 +/- 0.5 kg) in the energy metabolism and
      energy intake subsets, respectively, did not differ between groups and were
      comparable to changes seen in a larger group of patients who received rhGH in a
      randomized, double blind, placebo-controlled multicenter study. In the energy
      metabolism subset, REE (+232 +/- 69 Cal/day; P = 0.020) and lipid oxidation (+3.1
      +/- 1.0 Cal/kg LBM.day; P = 0.016) increased, whereas protein oxidation decreased
      (-1.3 +/- 1.0 Cal/kg LBM.day; P = 0.027) during rhGH therapy. These changes in
      REE and substrate oxidation are comparable to changes we noted previously in a
      study of the effects of short term rhGH treatment in patients with HIV-associated
      wasting. Moreover, the sustained increases in lipid oxidation are consistent with
      the decreases in body fat content that occur with rhGH treatment. In the energy
      intake subset, a trend for increased daily energy intake (+203 +/- 262 Cal; P =
      0.456) is obviated when adjustments for changes in weight or LBM are made (+1.3
      +/- 4.0 and -0.5 +/- 5.0 Cal/kg BW and LBM, respectively). Taken together, these
      results demonstrate that increases in weight and LBM that occur with chronic rhGH
      therapy are accompanied by sustained increases in REE and lipid oxidation and
      decreases in protein oxidation. These changes in body composition occur without a
      significant increase in energy intake and may, instead, represent a
      redistribution of body energy stores.

PMID- 9589653
TI  - Hashimoto's thyroiditis and insulin-dependent diabetes mellitus: differences
      among individuals with and without abnormal thyroid function.
AB  - Insulin-dependent diabetes mellitus probands from the Familial Autoimmune and
      Diabetes Study were evaluated for autoimmune thyroid disease (n = 265). The
      prevalence of Hashimoto's thyroiditis was 26.6%; 42.0% of these individuals were
      euthyroid, and 58.0% were hypothyroid. There was a female predominance among
      hypothyroid and euthyroid Hashimoto's cases compared to those with no thyroid
      disease (75% vs. 72.4% vs. 41.6%; P < 0.001). Insulin-dependent diabetes mellitus
      patients with hypothyroid Hashimoto's thyroiditis were more likely to report
      another autoimmune disease compared to euthyroid Hashimoto's patients or
      individuals with no thyroid disease (30.8% vs. 17.2% vs. 13.9%; P < 0.01). Sex
      specific analysis revealed that this difference was significant for men but not
      for women. Both euthyroid and hypothyroid Hashimoto's cases were more likely to
      have a family history of the disease (66.7% vs. 69.2% vs. 47.7%; P < 0.05). No
      differences were observed in the prevalence of DQA1*0501-DQB1*0201 or DQA1*0301
      DQB1*0302 across the three groups. Body mass index, lipid levels, glycemic
      control, and diabetes complications were also similar. However, euthyroid
      Hashimoto's women were more likely to report spontaneous abortions than those
      with hypothyroid Hashimoto's thyroiditis or no thyroid disease (23.8% vs. 61.5%
      vs. 29.1%; P < 0.05). These data suggest that gender-specific risk factors may be
      primary determinants of Hashimoto's thyroiditis and other autoimmune diseases
      among women. However, disease-specific determinants may also increase
      susceptibility to other autoimmune diseases.

PMID- 9589654
TI  - Dietary sodium restriction impairs insulin sensitivity in noninsulin-dependent
      diabetes mellitus.
AB  - Dietary sodium restriction has a variety of effects on metabolism, including
      activation of the renin-angiotensin system. Angiotensin II has complex metabolic
      and cardiovascular effects, and these may be relevant to the effects of both
      nonpharmacological and pharmacological interventions in noninsulin-dependent
      diabetes mellitus (NIDDM). We have assessed the effect of dietary sodium
      restriction on insulin sensitivity and endogenous glucose production in eight
      normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic
      clamp studies in a randomized, double-blind, placebo-controlled cross-over
      protocol after two 4-day periods on sodium replete (160 mmol/day) and sodium
      deplete (40 mmol/day) diets. Mean +/- SD 24-h urinary sodium was 197 +/- 76.0
      mmol (replete) and 67 +/- 19.5 mmol (deplete), P = 0.03. Insulin sensitivity was
      42.0 +/- 11.3 mumol/kg.min (replete) and 37.0 +/- 11.6 mumol/kg.min (deplete), P
      = 0.04 (a reduction of 12%). Blood pressure was 130 +/- 21/78 +/- 11 mmHg
      (replete) and 128 +/- 12/73 +/- 10 mmHg (deplete). Dietary sodium restriction may
      result in a decrease in peripheral insulin sensitivity in normotensive patients
      with NIDDM, possibly via an elevation in prevailing angiotensin II
      concentrations.

PMID- 9589655
TI  - Comparison of low and high dose corticotropin stimulation tests in patients with
      pituitary disease.
AB  - Tetracosactin [corticotropin-(1-24)] is used for clinical testing of
      adrenocortical responsiveness. The usual dose [high dose test (HDT)] is 250
      micrograms. With this test, patients with mild secondary adrenal insufficiency
      are usually not identified, thus putting them at risk of an adrenal crisis in
      stressful situations. It was recently reported that a tetracosactin test with
      approximately 1 micrograms [low dose test (LDT)] identifies patients with mild
      forms of pituitary-adrenal insufficiency. We performed both the HDT and the LDT
      in 35 control subjects and in 44 patients with pituitary disease, mostly
      pituitary tumors. In these patients, more sensitive reference tests for
      evaluating the pituitary-adrenal axis (insulin-induced hypoglycemia, metyrapone,
      and CRH tests) were also performed. In the HDT, plasma cortisol was measured 30
      and 60 min after tetracosactin injection; in the LDT (0.5 microgram/m2 body
      surface area), plasma cortisol was measured 20, 30, 40, 50, and 60 min
      postinjection. In 6 control subjects, tetracosactin plasma levels were also
      measured after injection. In the HDT, the correlation between 30 and 60 min
      cortisol levels was extremely high (r = 0.991; P < 0.0001), but the correlation
      of the LDT with the HDT at 30 min was also highly significant (r = 0.948; P <
      0.0001). The lower normal limit of cortisol responses (means of controls minus 2
      SD) at 30 min was lower in the LDT by 3.1 micrograms/dL (85 nmol/L) than in the
      HDT. Compared with the reference tests, the diagnostic sensitivities of the HDT
      and the LDT were almost identical. Both tests identified patients with moderately
      to severely pathological insulin and metyrapone tests, but not those with
      slightly pathological reference tests. In the HDT, plasma tetracosactin rose to
      more than 60,000 pg/mL shortly after injection. In the LDT, it rose to 1,900
      pg/mL. Both concentrations stimulate cortisol (supra-) maximally. Together, these
      data show that in pituitary disorders the results of the LDT and the HDT are
      almost identical. Plasma tetracosactin levels in the LDT still rise to levels
      that maximally stimulate the adrenal. Tetracosactin testing with low or high
      doses cannot generally replace the more expensive and cumbersome insulin or
      metyrapone tests.

PMID- 9589656
TI  - A case of Albright's hereditary osteodystrophy-like syndrome complicated by
      several endocrinopathies: normal Gs alpha gene and chromosome 2q37.
AB  - We report a sporadic case of Albright's hereditary osteodystrophy (AHO)-like
      syndrome with several endocrinopathies. A 37-yr-old woman had an appearance of
      AHO but did not have renal PTH resistance. Her case was complicated by non
      insulin-dependent diabetes mellitus with severe insulin resistance, central
      diabetes insipidus, and hyposecretion of GH. Most patients with AHO are found in
      a family of pseudohypoparathyroidism type-Ia and have a heterozygous mutation
      that inactivates the alpha-subunit of Gs (Gs alpha), the stimulatory regulator of
      adenylyl cyclase. Some sporadic cases occur in which patients with phenotype
      similar to AHO have a deletion of chromosome 2q37. However, in this patient, both
      the Gs alpha gene structure and the biological activity were normal. In addition,
      chromosome analysis revealed a normal pattern with no visible deletion of
      chromosome 2q37. Our findings suggest that one or more other factors may be
      involved in the pathogenesis of AHO-related disease.

PMID- 9589657
TI  - Growth hormone treatment prevents the decrease in insulin-like growth factor I
      gene expression in patients undergoing abdominal surgery.
AB  - Acquired GH resistance together with reduced skeletal muscle mass are found in
      patients with increased protein catabolism due, for example, to sepsis, trauma,
      or major surgery. Both administration of glutamine-containing parenteral
      nutrition and GH treatment have been found to diminish this catabolism. The
      effects of GH are mediated in part by insulin-like growth factor I (IGF-I) that
      is produced in the liver and locally in GH target tissues. The aim of this study
      was to investigate the effect of GH treatment on expression of the IGF-I gene and
      GH receptor (GHR) gene in skeletal muscle after major surgery. A new quantitative
      RT-PCR-based assay was established to measure IGF-I gene expression.
      Metabolically healthy patients, without significant preoperative weight loss, who
      were undergoing elective abdominal surgery were included in the study. Five
      patients (one woman and four men) were treated with daily injections of GH (0.3
      IU/kg.day) in addition to being given total parenteral nutrition including
      glutamine (0.28 g/kg.day). The control group consisted of eight patients (three
      women and five men), who were given glutamine-enriched total parenteral nutrition
      but no GH. A muscle biopsy was taken from the lateral portion of the quadriceps
      femoris muscle preoperatively (day 0) after induction of anesthesia. A second
      biopsy was taken under local anesthesia on postoperative day 3. Total ribonucleic
      acid (RNA) was extracted from the muscle biopsies, and IGF-I messenger RNA (mRNA)
      and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA
      and GHR mRNA levels were related to the expression of a housekeeping gene
      (cyclophilin). In the control group, IGF-I mRNA levels decreased from 1505 +/-
      265 (mean +/- SEM) transcripts/cpm cyclophilin on day 0 to 828 +/- 172 on day 3
      (P < 0.05). In contrast, IGF-I mRNA levels did not change in the GH-treated group
      (1188 +/- 400 transcripts/cpm cyclophilin on day 0 vs. 1089 +/- 342
      transcripts/cpm cyclophilin on day 3). No statistically significant changes were
      seen in GHR expression. We conclude that administration of GH prevents the
      reduction in IGF-I gene expression in skeletal muscle after abdominal surgery.

PMID- 9589658
TI  - Acute effects of recombinant human interleukin-6 on endocrine and central nervous
      sleep functions in healthy men.
AB  - Interleukin-6 (IL-6) is a proinflammatory cytokine that has been shown to
      mediate, in addition to immune reactions, various endocrine and central nervous
      components of the acute phase response. In this context, the present study aimed
      to specify the contributions of IL-6 to the regulation of pituitary-adrenal
      secretory activity and GH and TSH secretion, as well as to the regulation of
      central nervous sleep and mood in healthy men. Effects of a low dose of IL-6 (0.5
      microgram/kg body weight) were assessed, inducing plasma IL-6 concentrations
      closely comparable with those typically observed after infectious challenge. Each
      of the 16 male subjects participated in two 14-h sessions (between 1800 and 0800
      h), receiving either placebo or human recombinant IL-6 sc at 1900 h. Blood was
      collected repeatedly to determine plasma hormone levels, serum concentrations of
      cytokines, and C-reactive protein. Moreover, mood was assessed, and sleep
      recordings were obtained between 2300 and 0700 h. The cytokine induced a
      prolonged increased in plasma concentrations of ACTH and cortisol (P < 0.001),
      but led to a decrease in TSH concentrations (P < 0.01). In response to IL-6,
      subjects reported fatigue and felt more inactive and less capable of
      concentrating than after placebo. Sleep architecture was altered significantly by
      the cytokine. Slow-wave sleep was decreased during the first half and increased
      during the second half of sleep. Rapid eye movement sleep during the entire
      nocturnal sleep time was significantly decreased. After IL-6, body temperature
      rose slightly. C-reactive protein concentrations were dramatically increased 12.5
      h after substance administration (P < 0.001). IL-6 did not affect serum
      concentrations of IL-2, IL-8, interferon-alpha, and interferon-gamma. The results
      underscore the importance of IL-6 in the cascade of cytokines for the
      neuroendocrine response during the acute phase reaction. In addition, IL-6
      appears to be involved in changes of sleep and behavior accompanying infection
      and inflammatory disorders.

PMID- 9589659
TI  - Linkage analysis of candidate genes in autoimmune thyroid disease: 1. Selected
      immunoregulatory genes. International Consortium for the Genetics of Autoimmune
      Thyroid Disease.
AB  - Graves' and Hashimoto's diseases are autoimmune thyroid diseases in which the
      genetic contribution is complex. For this reason, identification of necessary
      susceptibility genes has been difficult. However, a number of immunoregulatory
      genes have been implicated by association studies, including: CTLA-4, a recently
      described protein involved in antigen presentation, located on chromosome 2q33;
      the T-cell receptor V alpha and V beta gene complexes, located on 14q11 and 7q35,
      respectively; and the Ig gene complex (IgH), located on 15q11. We used
      polymorphic microsatellite markers located within these genes, or gene complexes,
      to test for linkage (rather than association), to each of these candidates. Using
      markers within the loci allowed us to assume a fixed recombination fraction of
      0.01 in the tested model. Three hundred eight subjects from 48 multiplex families
      were studied, with 142 affected subjects. Using this set of families, we have
      previously shown evidence of linkage with a major susceptibility locus for
      Graves' disease (GD-1) on 14q24.3-31, with a maximum lod (logarithm + odds) score
      of 2.1, at a penetrance of 80% and with a dominant mode of inheritance. In the
      present study, we obtained consistently negative lod scores for each of the
      candidate genes, assuming either dominant or recessive modes of inheritance.
      These data, therefore, showed evidence against linkage with all the candidate
      genes. Unlike association studies, linkage analyses detect major genetic
      influences on disease susceptibility exerted by the linked loci. The lack of
      linkage for the immunoregulatory genes that were studied indicated, therefore,
      that they were not major contributors to disease etiology.

PMID- 9589660
TI  - Maternal corticotropin-releasing hormone is increased with impending preterm
      birth.
AB  - The objective of this study was to test the hypothesis that maternal CRH
      concentrations are elevated in women experiencing threatened preterm labor who
      subsequently give birth within 24 h compared to those in women who do not. We
      also characterized the changes in maternal plasma cortisol, ACTH, corticosteroid
      binding capacity (CBC), and CRH concentrations in 28 healthy pregnant women
      between 20-38 weeks gestation. Overall, maternal plasma CRH concentrations were
      significantly greater (P < 0.05) in those women giving birth within 24 h (1343.3
      +/- 143.9 pg/mL; n = 81) compared to those in women who did not (714.5 +/- 64.8
      pg/mL; n = 144) or those in normal subjects. This difference was present between
      28-36 weeks, but not 24-28 weeks gestation. The ratio of maternal cortisol to CBC
      was also significantly greater (P < 0.05; 0.65 +/- 0.04; n = 82) in women giving
      birth within 24 h than in those who did not (0.55 +/- 0.02; n = 136). This
      difference was significant at all gestational ages studied. Elevated CRH
      concentrations and bioavailability of free cortisol may both be implicated in the
      pathogenesis of preterm labor in some women. Further prospective clinical trials
      are warranted to determine the positive and negative predictive values of
      maternal CRH concentrations and/or the ratio of cortisol/CBC for identifying
      women with threatened preterm labor destined to give birth within 24 h.

PMID- 9589661
TI  - Protein kinase A, protein kinase C, and Ca(2+)-regulated expression of 21
      hydroxylase cytochrome P450 in H295R human adrenocortical cells.
AB  - The physiological importance of adrenal 21-hydroxylase cytochrome P450 (CYP21)
      expression is clearly demonstrated by 21-hydroxylase deficiency, which results in
      adrenal hyperplasia and over-production of C19 steroids, leading to virilization.
      The mechanisms regulating normal expression of this key enzyme in human
      adrenocortical cells are ill defined. Herein we examine the role of the calcium,
      protein kinase C, and protein kinase A signaling pathways in the expression of
      CYP21 messenger ribonucleic acid (mRNA) using the H295R human adrenocortical cell
      model. Forskolin (10 mumol/L) treatment caused a progressive increase in CYP21
      mRNA levels (maximum, 4-fold; P < 0.05) over 36 h of treatment, whereas
      angiotensin II (AII; 10 nmol/L) produced a smaller, biphasic rise (maximum, 1.8
      fold at 12 h; P < 0.05). K+ (14 mmol/L) also induced a time-dependent (maximal,
      1.5-fold at 12 h; P < 0.05) and dose-dependent (P < 0.05 12 mmol/L or above at 20
      h) rise in CYP21 mRNA levels. The action of forskolin was reproduced by dibutyryl
      cAMP, confirming the involvement of cAMP in this response. The action of AII was
      greater than that of K+ or the calcium channel agonist BAYK8644, suggesting that
      AII action was not solely through the Ca2+ signaling pathway. The action of AII
      was reproduced and indeed exceeded by the protein kinase C activator 12-O
      tetradecanoylphorbol 13-acetate (TPA; 10 nmol/L; 5.5-fold increase; P < 0.05).
      The actions of forskolin alone were not significantly increased by combined
      treatment with AII, suggesting neither synergy nor attenuation of the effects of
      protein kinase A activation. This was further demonstrated at the level of mRNA
      and 21-hydroxylase activity by the observation that the effect of forskolin and
      TPA in combination did not exceed that of TPA alone. Inhibition of protein
      synthesis with cycloheximide blocked induction of CYP21 as well as type II 3 beta
      hydroxysteroid dehydrogenase (3 beta HSDII) mRNA expression in response to AII,
      forskolin, and dibutyryl cAMP, but had no effect on 17 alpha-hydroxylase
      cytochrome P450 (CYP17) or cholesterol side-chain cleavage cytochrome P450
      (CYP11A) mRNA. Together, these findings were remarkably similar to those of our
      previous studies regarding mechanisms regulating 3 beta HSDII expression and
      underline the existence of a subset of steroidogenic enzymes regulated positively
      (CYP21 and 3 beta HSDII) as opposed to negatively (CYP17 and CYP11A) by the
      protein kinase C signaling pathway. The additional finding of a small induction
      of CYP21 expression in response to increased Ca2+, as previously reported for
      CYP17, but not 3 beta HSDII, expression, also demonstrates that the mechanisms of
      control of CYP21 and 3 beta HSDII are not identical. This latter finding may also
      relate to how CYP21 as well as CYP17 expression continues in the zona reticularis
      after adrenarche, whereas 3 beta HSD expression declines.

PMID- 9589662
TI  - Immortalized human pituitary cells express glycoprotein alpha-subunit and
      thyrotropin beta (TSH beta).
AB  - A major problem in the study of human pituitary cells is their lack of
      proliferative capacity in vitro. To address this issue, we have infected normal
      human, postmortem pituitary cells in monolayer culture with a temperature
      sensitive (tsA58) mutant of SV40 large T antigen. Several epithelial-like
      colonies were isolated; and one, designated CHP2, has been studied in detail to
      identify its functional characteristics. CHP2 cells have undergone more than 150
      culture passages and retain an epithelial morphology. They exhibit tight
      temperature-dependent growth, in the presence and absence of serum, with cell
      division at 33 C and growth inhibition at 39 C. CHP2 cells, at both temperatures,
      showed diffuse immunostaining for human alpha-subunit and focal staining for TSH
      beta. Gene expression was confirmed by RT-PCR and sequencing. TRH and GnRH
      receptors were not detectable, and their absence was confirmed by their lack of
      effects on intracellular calcium and inositol phospholipids. Cytogenetic analysis
      showed that the cells had a modal peak in the diploid range and a smaller peak in
      the tetraploid range. There was also a consistent loss of chromosome 22 and a
      normal chromosome 2 homologue, the latter being replaced by one of two chromosome
      2 markers, M2A or M2B. In conclusion, we have immortalized human pituitary cells
      using SV40 tsT, from which we have cloned a cell line expressing alpha-subunit
      and TSH beta.

PMID- 9589663
TI  - Pronostic and therapeutic consequences of Gs alpha mutations in somatotroph
      adenomas.
AB  - Human pituitary somatotroph adenomas can be associated with mutations of the s
      alpha-subunit of G proteins. However, the impact of the gsp mutations on the
      tumoral phenotype is not well understood at present. This study aims to determine
      whether the detection of this mutation could impact on the management of
      acromegalic patients. We examined 30 acromegalic patients; 8 were gsp positive,
      and 22 were gsp negative. The gsp-positive adenomas appeared to secrete
      significantly more when the ratio of basal GH level/tumor size was considered. A
      better octreotide sensitivity of mutated adenomas was clearly shown under in vivo
      (short and long term) and in vitro conditions. During the acute octreotide test,
      the GH nadir was significantly lower in the gsp-positive adenomas (85% of maximal
      inhibition vs. 52%). Eighteen patients were treated with octreotide (300
      micrograms/day) for at least 3 months before surgery: the percent inhibition of
      GH hypersecretion was higher in gsp-positive adenomas (76% vs. 47%). In cell
      culture, the octreotide-induced inhibition of GH release was significantly higher
      in gsp-positive adenomas (71% vs. 30%). Finally, during 2 yr of postoperative
      follow-up, GH hypersecretion was controlled in all patients with gsp mutation
      even in those in whom tumoral tissue remained after surgery. On the contrary, in
      the gsp-negative group, octreotide treatment was unable to control hypersecretion
      in 4 patients bearing tumoral remnants. The Gs alpha mutation could, therefore,
      be a new marker to foresee the susceptibility of the tumor to be controlled by
      somatostatin analogs, which improves prognosis.

PMID- 9589664
TI  - The pathophysiology of circulating corticotropin-releasing hormone-binding
      protein levels in the human.
AB  - To establish the factors that modulate circulating CRH-binding protein (CRH-BP)
      levels, we measured plasma CRH-BP in patients with a variety of endocrine and
      systemic disorders. CRH-BP was measured by RIA. Young women have higher plasma
      levels of CRH-BP than young men [females (n = 18), mean +/- SEM, 145 +/- 7; males
      (n = 20), 99 +/- 6 ng/mL; P < 0.0001], but levels do not fall with the menopause
      or vary during the menstrual cycle and are unaffected by estrogen replacement
      therapy. Levels were lower in patients with liver disease than in healthy men (26
      +/- 3 vs. 99 +/- 6; P < 0.0001) and were elevated in chronic renal failure
      compared to those in healthy women (211 +/- 11.2 vs. 145 +/- 7; P < 0.01). Levels
      were unaffected by fasting in men or women (male fasted, 97 +/- 11; male fed, 97
      +/- 8; female fasted, 136 +/- 9; female fed, 152 +/- 10). Dexamethasone treatment
      lowered CRH-BP in all subjects (129 +/- 8 vs. 111 +/- 9; P < 0.003). Similarly,
      CRH-BP levels were lower in patients with Cushing's syndrome (all female) than in
      healthy female controls (median, 82; range, 53-106; vs. median, 142; range, 101
      190; P < 0.0001). In Cushing's patients, an i.v. bolus of 100 micrograms human
      CRH further lowered plasma CRH-BP at 15 min (81 +/- 5 vs. 50 +/- 4; P < 0.0003).
      Plasma levels of CRH-BP are higher in women than men, but this is unrelated to
      circulating estrogen levels. The low levels in liver disease and the high levels
      in renal failure support its hepatic origin and the kidneys as the route of
      clearance from plasma. The ability of glucocorticoids and exogenous CRH to lower
      plasma CRH-BP levels and of CRH-BP to modulate the bioactivity of circulating CRH
      suggest that the protein may be an important regulator of circulating CRH or
      related ligands.

PMID- 9589665
TI  - Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing
      hormone + arginine as provocative tests for the diagnosis of GH deficiency in
      adults.
AB  - There is now wide consensus that, within an appropriate clinical context, GH
      deficiency (GHD) in adults must be shown biochemically by provocative testing of
      GH secretion and that appropriate cut-off limits have to be defined for each
      provocative test. Insulin-induced hypoglycemia (ITT) is indicated as the test of
      choice, and severe GHD, to be treated with recombinant human GH replacement, is
      defined by a GH peak response to ITT of less than 3 micrograms/L. GHRH + arginine
      (GHRH + ARG) is one of the most promising tests in alternative to ITT. In fact,
      it has been reported as a potent, reproducible, and age-independent test and that
      it is able to distinguish between GHD and normal adults. The aim of the present
      study was to compare the GH response to ITT and GHRH + ARG in a large group of
      hypopituitary adults (n = 40; 29 male and 11 female; age: 36.4 +/- 2.1 yr). The
      third centile limit of the peak GH response to ITT has been reported as 5
      micrograms/L, whereas in our lab, that to GHRH + ARG is 16.5 micrograms/L. In
      hypopituitary adults, the mean peak GH response to ITT (1.5 +/- 0.2 micrograms/L,
      range: 0.1-8.5 micrograms/L) was lower (P < 0.001) than that to GHRH + ARG (3.0
      +/- 0.4 micrograms/L, range 0.1-12.0 micrograms/L), though there was positive
      correlation (r = 0.61, P < 0.001) between the GH responses to the 2 tests. The
      peak GH response to GHRH + ARG, but not that to ITT, was positively (though
      weakly) associated with insulin-like growth factor-I levels (r = 0.35, P < 0.03).
      Childhood and adult onset GHD patients, as well as patients with single and
      multiple pituitary insufficiencies, had similar peak GH responses to ITT or GHRH
      + ARG. Analyzing individual GH responses, 4/40 (10%) of the hypopituitary
      patients had GH peaks higher than 5 micrograms/L after ITT; moreover, 3 other
      patients (7%) had GH peaks, after ITT, higher than 3 micrograms/L. On the other
      hand, after GHRH + ARG, all patients had GH peaks lower than 16.5 micrograms/L,
      whereas 21/40 (52.5%) had GH peaks higher than 3 micrograms/L. Because 3
      micrograms/L is the arbitrary cut-off for ITT, the third centile limit of which
      is 5 micrograms/L, we arbitrarily considered 9 micrograms/L as the cut-off point
      for GHRH + ARG. It is noteworthy that 37/40 (92.5%) patients had a GH peak, after
      GHRH + ARG, below this limit. In conclusion, our present results confirm that the
      ITT test is a reliable provocative test for the diagnosis of adult GHD, whereas
      they show that the GHRH + ARG test is, at least, as sensitive as the ITT test
      (provided that appropriate cut-off limits are considered). Note that even the
      arbitrary cut-off point below which severe GHD is demonstrated has to be
      appropriate to the potency of the test.

PMID- 9589666
TI  - Biochemical assessment of Cushing's disease in patients with corticotroph
      macroadenomas.
AB  - The majority of cases of Cushing's disease are due to an underlying pituitary
      corticotroph microadenoma (< or = 10 mm). Corticotroph macroadenomas (> 10 mm)
      are a less common cause of Cushing's disease, and little is known about specific
      clinical and biochemical findings in such patients. To define further the
      clinical characteristics of patients with corticotroph macroadenomas, we
      performed a retrospective review of Cushing's disease due to macroadenomas seen
      at Massachusetts General Hospital between 1979 and 1995. Of 531 patients
      identified with a diagnostic code of Cushing's syndrome, 20 were determined to
      have Cushing's disease due to a macroadenoma based on radiographic evidence of
      pituitary adenoma greater than 10 mm and pathological confirmation of a pituitary
      adenoma. A comparison review of charts of 24 patients with Cushing's disease due
      to corticotroph microadenomas identified on the basis of radiographic evidence of
      a normal pituitary gland or a pituitary adenoma 10 mm or less in diameter was
      also performed. The mean ages of the patients (+/- SD) with macroadenomas and
      microadenomas were similar (39 +/- 12 and 38 +/- 14 yr, respectively). The
      baseline median 24-h urine free cortisol (UFC) excretion was 1341 nmol/day
      (range, 304-69,033 nmol/day) and 877 nmol/day (range, 293-2,558 nmol/day) for
      macroadenoma and microadenoma patients, respectively (P = 0.058). After the 48-h
      high dose dexamethasone suppression test, UFC decreased by 77 +/- 19% (mean +/-
      SD) and 91 +/- 7% in macroadenoma and microadenoma subjects, respectively (P =
      0.04). Fifty-six percent of macroadenoma patients and 92% of microadenoma
      patients had greater than 80% suppression of UFC after high dose dexamethasone
      administration (P = 0.03). The baseline median 24-h urinary 17-hydroxysteroid (17
      OHCS) excretion was 52 mumol/day (range, 25-786 mumol/day) and 44 mumol/day
      (range, 17-86 mumol/day) for macroadenoma and microadenoma subjects, respectively
      (P = 0.09). After the standard high dose dexamethasone suppression test, 17-OHCS
      excretion decreased by 46 +/- 33% and 72 +/- 22% for macroadenoma and
      microadenoma subjects, respectively (P = 0.02). Fifty-three percent of patients
      with macroadenomas and 86% of patients with microadenomas had greater than 50%
      suppression of 17-OHCS after high dose dexamethasone administration (P = 0.02).
      Baseline plasma ACTH values were above the normal range in 83.3% of macroadenoma
      patients and in 45% of microadenoma subjects (P = 0.05). Tumors were
      immunostained with the MIB-1 antibody for Ki-67 to investigate proliferation in
      the adenomas. There was a trend for a higher Ki-67 labeling index in corticotroph
      macroadenomas, and seven (44%) macroadenomas vs. three (18%) microadenomas had
      labeling indexes greater than 3%, but this was not statistically significant. In
      summary, corticotroph macroadenomas are often associated with less glucocorticoid
      suppressibility than the more frequently occurring microadenomas. Therefore, the
      lack of suppression of UFC or 17-OHCS after the administration of high dose
      dexamethasone in a patient with Cushing's disease does not necessarily imply the
      presence of ACTH-independent Cushing's syndrome and is more commonly seen in
      patients with corticotroph macroadenomas than in those with microadenomas.
      Increased plasma ACTH concentrations are typical of patients with corticotroph
      macroadenomas and may be a more sensitive indicator of neoplastic corticotrophs
      than the UFC or 17-OHCS response to standard high dose dexamethasone testing.

PMID- 9589667
TI  - Constitutively active Gs alpha is associated with an increased phosphodiesterase
      activity in human growth hormone-secreting adenomas.
AB  - Because phosphodiesterase (PDE) expression and activity are controlled by cAMP,
      we investigated whether activating mutations of Gs alpha gene that occur in human
      GH-secreting adenomas are associated with increased PDE activity. We studied 10
      adenomas with wild-type Gs alpha (gsp-) and 8 with mutant Gs alpha (gsp+).
      Although, in the absence of PDE inhibitors, intracellular cAMP levels were
      similar in gsp+ e gsp- adenomas, the PDE blockade with 3-isobutyl-1
      methylxanthine induced a marked increase in cAMP in all but one gsp+ adenoma (%
      increase: from 77 to 2900) and a slight rise in only 2 gsp-. Similar results were
      obtained with the PDE4 selective inhibitor 4-[3-(cyclopentyloxy)-4
      methoxyphenyl)]-2-pyrrolidinone. In vitro GH release was significantly higher in
      gsp+ than in gsp- adenomas (315 +/- 158 vs. 82 +/- 53 micrograms/well; P < 0.01),
      and PDE blockade caused a further increase in 3 of 5 gsp+ adenomas but not in gsp
      tumors. By direct measurement, PDE activity was about 7-fold higher in gsp+ than
      in gsp- adenomas (320 +/- 213 vs. 48 +/- 23 pmol/min.mg protein; P < 0.05) and
      was largely 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone sensitive.
      This study first demonstrates that activating mutations of the Gs alpha gene that
      naturally occur in pituitary adenomas is associated with an increased PDE
      activity that might, at least partially, counteract the constitutive activation
      of the cAMP-dependent pathway.

PMID- 9589668
TI  - High frequency of rearrangement of the RET protooncogene (RET/PTC) in Chinese
      papillary thyroid carcinomas.
AB  - The activation of RET protooncogene, through chromosomal translocation, is unique
      to papillary thyroid carcinomas. Rearrangement of the RET kinase domain to 3
      partner genes has been described, of which the RET/PTC1 is the most common. To
      investigate the frequency of RET rearrangement in Chinese papillary thyroid
      carcinomas, we have performed RT-PCR to amplify specific RET/PTC transcripts.
      Among the papillary thyroid carcinomas of 11 patients examined, we have
      identified 2 containing RET/PTC1, 3 containing RET/PTC2, and 1 containing
      RET/PTC3 oncogenes. Although the cause of the high frequency of RET/PTC oncogenes
      in Chinese papillary thyroid carcinomas is unknown, our study suggests that RET
      rearrangement is an important genetic lesion underlying the development of
      thyroid papillary carcinoma in Taiwan.

PMID- 9589669
TI  - Effect of tamoxifen on serum lipid metabolism.
AB  - The effect of tamoxifen, an antiestrogenic agent, on lipid metabolism was studied
      in postmenopausal patients with breast cancer who received the drug for
      postoperative adjuvant treatment following mastectomy. To measure total
      cholesterol and triglyceride concentrations, fasting blood samples were collected
      before and 2 months after the initiation of tamoxifen therapy from 16 patients
      who satisfied the study criteria. All patients were normolipidemic before
      tamoxifen was administered. Control samples were obtained from
      hypertriglyceridemia patients who were free from breast cancer. Marked
      hypertriglyceridemia was observed in 3 of 16 patients after tamoxifen treatment.
      The activity of lipoprotein lipase and hepatic triglyceride lipase, the key
      enzymes of triglyceride metabolism, decreased significantly in all of 16 patients
      as a result of tamoxifen treatment (P = 0.008 and P = 0.007, respectively).
      However, the mean mass of lipoprotein lipase significantly increased (P = 0.011)
      after tamoxifen treatment. We therefore conclude that tamoxifen might increase
      inactive lipoprotein lipase. Because marked hyperlipidemia is a potent risk
      factor for life-threatening acute pancreatitis and arteriosclerosis, plasma lipid
      levels should be tested periodically during tamoxifen treatment, even if the
      patients are normolipidemic during the pretreatment stage.

PMID- 9589671
TI  - Growth hormone status during long-term hexarelin therapy.
AB  - Hexarelin, a powerful GH-releasing peptide, is capable of causing profound GH
      release in normal subjects after oral, intranasal, i.v., and s.c. administration.
      The effect of long-term administration on GH levels in adults is unknown. We
      have, therefore, assessed the effects of 16 weeks of twice-daily s.c. hexarelin
      therapy (1.5 micrograms/kg BW) on the GH response to a single injection of
      hexarelin, and also the GH response to hexarelin 4 weeks after cessation of
      hexarelin therapy. We have also assessed the effects of chronic hexarelin therapy
      on serum insulin-like growth factor (IGF)-I, IGF binding protein-3, markers of
      bone formation (osteocalcin, procollagen-type-III-N-terminal-peptide, and C
      terminal propeptide of type I collagen), and resorption (urinary
      deoxypyridinoline and pyridinoline), body composition, and bone mineral density.
      The mean (+/- SEM) area under the GH curve (AUCGH) at weeks 0, 1, 4, 16, and 20
      were 19.1 +/- 2.4 micrograms/L.h, 13.1 +/- 2.3 micrograms/L.h, 12.3 +/- 2.4
      micrograms/L.h, 10.5 +/- 1.8 micrograms/L.h, and 19.4 +/- 3.7 micrograms/L.h,
      respectively. There was a significant change in AUCGH over the study period (P =
      0.0003). Further analysis showed that, compared with baseline, the decrease in
      AUCGH at week 4 and week 16 were significant (P < 0.05 and P < 0.01,
      respectively). Four weeks after completion of hexarelin therapy, the AUCGH
      increased significantly, compared with AUCGH at week 16 (P < 0.05), and was not
      significantly different from that at week 0. Serum IGF-I and IGF binding protein
      3 did not change significantly over the 20-week period (P = 0.24 and P = 0.74,
      respectively). Of the bone markers measured, only serum C-terminal propeptide of
      type I collagen changed significantly and was higher at week 16, compared with
      baseline (P = 0.019). Total body fat, lean body mass, and bone mineral density
      had not changed significantly at week 16, compared with baseline (P = 0.6, P =
      0.3, and P = 0.3, respectively). In summary, we have demonstrated that chronic
      hexarelin therapy results in a partial and reversible attenuation of the GH
      response to hexarelin. In the present study, the biological impact of this
      hexarelin schedule on the GH-IGF-I axis seems to be minimal. The therapeutic
      potential of chronic hexarelin requires further investigation.

PMID- 9589670
TI  - Troglitazone regulation of glucose metabolism in human skeletal muscle cultures
      from obese type II diabetic subjects.
AB  - To determine the effects of troglitazone on abnormal skeletal muscle glucose
      metabolism, muscle cultures from type II diabetic patients were grown for 4-6
      weeks and then fused for 4 days either without or with troglitazone (1-5
      micrograms/mL; chronic studies) or had troglitazone added for 90 min (1-5
      micrograms/mL) at completion of fusion (acute studies). Acute troglitazone
      treatment stimulated glucose uptake, but not glycogen synthase (GS) activity 2
      fold (P < 0.05) in a dose-dependent fashion and to the same extent as the
      addition of maximal (33 nmol/L) insulin. Maximal chronic troglitazone (5
      micrograms/mL for 4 days) increased both glucose uptake (from 9.0 +/- 1.5 to 40.9
      +/- 8.1 pmol/mg protein.min; P < 0.05) and GS fractional velocity (from 5.4 +/-
      0.7% to 20.6 +/- 6.3%; P < 0.05) by approximately 4-fold. At each concentration
      of chronic troglitazone, glucose uptake rates were similar in the absence and
      presence of maximal (33 nmol/L) insulin concentrations. In contrast, insulin
      stimulated GS activity was greater (P < 0.05) when maximal chronic troglitazone
      and acute insulin were combined than when chronic troglitazone alone was used.
      After 4 days of troglitazone, GLUT1 messenger ribonucleic acid and protein
      increased about 2-fold (P < 0.05) without a change in GLUT4 or GS messenger
      ribonucleic acid and protein. We conclude that troglitazone has both acute and
      chronic effects to improve skeletal muscle glucose metabolism of obese type II
      diabetic subjects. These effects involve direct insulin mimetic stimulatory
      actions as well as indirect insulin-sensitizing properties.

PMID- 9589672
TI  - A recurrent missense mutation in the KAL gene in patients with X-linked
      Kallmann's syndrome.
AB  - Kallmann's syndrome (KS) is defined by the association of hypogonadotropic
      hypogonadism and anosmia or hyposmia. Segregation analysis in familial cases has
      demonstrated diverse inheritance patterns, suggesting the existence of several
      genes regulating GnRH secretion. Genetic defects have been demonstrated in the
      KAL gene, located on the Xp22.3 region, explaining the X-linked form of the
      disease. We report molecular findings regarding the KAL gene in 12 unrelated
      males with X-linked KS. PCR of the 14 exons of the KAL gene was performed on
      genomic DNA. PCR products of all exons were purified and sequenced. Genetic
      defects in the KAL gene were found in 7 patients. One exhibits a deletion from
      exon 3 to exon 5. Six individuals present a previously unidentified missense
      mutation in exon 11, consisting of a G to A substitution at codon 514 (GAA to
      AAA). In the remaining 5 individuals, no mutations were observed. We also found
      three different polymorphic changes. The first one, in exon 2, had not been
      reported previously. The other two were located at exons 11 and 12. The deletion
      described, comprises only part (exon 5) of the coding region of the first
      fibronectin type III-like repeat of the KAL protein. The rest of the deletion
      comprises part of the conserved cysteine-rich N-terminal region that corresponds
      to the whey acidic protein motif. The same missense mutation was found in 6 of
      the 12 patients, indicating the possibility that it derived from a common
      ancestor or suggesting the presence of a hot spot in this region of the gene.

PMID- 9589673
TI  - The insulin-like growth factor axis and growth in children with chronic renal
      failure: a report of the Southwest Pediatric Nephrology Study Group.
AB  - Children with chronic renal failure (CRF) are often growth recarded despite
      normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies
      suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF
      serum contribute to CRF growth failure. This report characterizes the
      relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF
      children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost
      exclusively in the 150-kDa fractions of normal serum, where their molar
      stoichiometry was approximately 1:1. However, similar chromatography of CRF serum
      found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and
      large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF
      serum, IGFBP-3 was present in normal amounts, but a greater than normal amount
      was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children
      with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs
      in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa
      fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These
      data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150
      kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but
      insufficient IGF is released to overcome the growth-inhibiting effects of these
      excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and
      IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases
      sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the
      35-kDa fractions of CRF serum.

PMID- 9589674
TI  - Increased pulsatile, but not basal, growth hormone secretion rates and plasma
      insulin-like growth factor I levels during the periovulatory interval in normal
      women.
AB  - The secretion of GH changes during the menstrual cycle, exhibiting high levels
      during the periovulatory phase (PO). Previous studies have not investigated
      whether this difference in GH status is due to increased secretion or reduced
      clearance of pituitary GH and amplified pulsatile vs. basal GH secretion. It is
      also unclear whether the PO phase is accompanied by changes in circulating
      insulin-like growth factor I (IGF-I). In this study we investigated the 24-h GH
      release patterns in the early follicular (EF) vs. the periovulatory menstrual
      phase in the same individuals. Ten young (aged 24-34 yr) healthy women with
      regular menses were studied with deconvolution analysis of GH profiles obtained
      by blood sampling every 20 min for 24 h, followed by an arginine stimulation
      test. A high sensitivity immunofluorometric GH assay was used. All women were
      studied in both the EF and PO phases in random order. There were no differences
      in the basal GH secretion rate or GH half-life during the two phases. The number
      of GH secretory bursts identified during the 24-h sampling period was
      significantly increased during the PO (13.3 +/- 0.5) compared to the EF (10.3 +/-
      0.6) phase (P = 0.002); conversely, the mean interburst interval was shorter in
      the PO (107 +/- 5 min) than in the EF (134 +/- 8 min) phase (P = 0.004). There
      was no difference in GH pulse mass (P = 0.13) or amplitude (P = 0.21) between the
      two phases. The pulsatile GH production rate (milligrams per L/24 h) was
      significantly elevated during the PO (61 +/- 6) compared to that during the EF
      (37 +/- 8; P = 0.004). Increased total GH pulse area was confirmed by Cluster
      analysis (P = 0.027). Furthermore, the 24-h mean serum GH concentration was
      significantly increased in the PO (1.4 +/- 0.1 mg/L) vs. that in the EF (0.9 +/-
      0.1 mg/L; P = 0.002). There was a positive correlation between estradiol (E2) and
      GH secretory pulse amplitude, frequency, and mean 24-h serum GH concentration in
      the PO cycle phase, indicating E2 to be a major statistical determinant of GH
      secretion. Serum GH increased significantly after arginine infusion in both
      phases (P < 0.001), whereas there was no difference between the two cycle phases
      (P = 0.20). Serum IGF-I levels were increased during the PO phase (253 +/- 20
      mg/L) compared to those during the EF phase (210 +/- 16 mg/L; P = 0.03), whereas
      serum IGF-binding protein-3, IGF-II, and GH-binding protein were similar during
      the two phases. This study unequivocally documents elevated GH levels during the
      PO phase of the menstrual cycle, mediated by increased GH production rate and
      burst frequency. The concomitant increase in serum IGF-I suggests a central
      stimulation of the GH-IGF-I axis, which may be mediated by endogenous E2 levels.

PMID- 9589675
TI  - Defects of insulin action and skeletal muscle glucose metabolism in growth
      hormone-deficient adults persist after 24 months of recombinant human growth
      hormone therapy.
AB  - We have previously reported that GH-deficient (GHD) adults are severely insulin
      resistant. In the present study, we determined the effects of 6 months (n = 7)
      and 24 months (long-term; n = 11) of recombinant human GH (rhGH) therapy
      (approximately 0.22 IU/kg.week) on body composition and fasting biochemical
      (including lipid) parameters, and baseline and insulin-stimulated: 1) rates of
      hepatic glucose production, total glucose disposal (Rd), total glycolysis (GF)
      and glucose storage (GS); and 2) skeletal muscle glucose processing [using the
      euglycemic-hyperinsulinemic (approximately 60 mU/L) clamp technique with
      tritiated glucose infusion coupled with skeletal muscle biopsies]. To allow
      baseline comparison, these measurements were also obtained from 10 control
      subjects matched to the pretreated GHD adults for age, sex, and body mass index.
      Long-term rhGH therapy in GHD adults induced significant improvements in fat
      mass, abdominal fat mass and fat free mass, and reductions in fasting cholesterol
      and low-density lipoprotein-cholesterol levels (P < 0.05-0.01 vs. pretreatment
      values). However, there was a significant increase in fasting insulin (13.1 +/-
      0.9 vs. 8.6 +/- 1.1 mU/L; P < 0.01) and connecting peptide (0.56 +/- 0.05 vs.
      0.41 +/- 0.06 nmol/L; P < 0.05). Although rates of baseline hepatic glucose
      production, GF, and GS were unchanged, the insulin-stimulated increment (delta)
      in Rd, GF, and GS remained markedly attenuated in the long-term rhGH-treated GHD
      adults [pretreatment: delta Rd 16.6 +/- 3.4, delta GF 3.0 +/- 1.2, delta GS 13.6
      +/- 3.0 vs. 24 months of rhGH: delta Rd 17.2 +/- 3.3, delta GF 3.1 +/- 0.9, delta
      GS 14.1 +/- 2.5 vs. controls: delta Rd 42.6 +/- 4.3, delta GF 9.2 +/- 1.9, delta
      GS 35.9 +/- 4.5 mumol/kg fat free mass.min; P < 0.05-0.01 vs. controls].
      Additionally, there was a sustained reduction in the insulin-stimulated skeletal
      muscle glycogen synthase fractional velocity (pretreatment: 0.29 +/- 0.03 vs. 24
      months of rhGH: 0.24 +/- 0.03 vs. controls: 0.48 +/- 0.04; both P < 0.05 vs.
      controls), which was accompanied by a sustained 44% decrease in baseline glycogen
      content and a 70% increase in baseline im glucose concentrations in the presence
      of low-to-normal glucose 6-phosphate levels and persisting euglycemia. Stepwise
      regression analysis revealed that body weight and fasting free fatty acid and
      high-density lipoprotein (HDL)-cholesterol accounted for 82% of the variance in
      the insulin sensitivity index in long-term rhGH-treated adults, and that the 24
      month fasting insulin-like growth factor 1 was a negative predictor of the change
      in insulin sensitivity (r = -0.82; P < 0.01). In conclusion, despite improvements
      in body composition and lipid profiles, the severe defects of in vivo insulin
      sensitivity and skeletal muscle intracellular glucose phosphorylation and
      glycogen synthase activity, which are associated with modestly elevated insulin
      like growth factor 1 levels, normal free fatty acid levels, and the development
      of hyperinsulinemia, persist with long-term rhGH therapy.

PMID- 9589676
TI  - Hypothalamic dysfunction in "cured" acromegaly is treatment modality dependent.
AB  - The current definition of cure after treatment for acromegaly stipulates a
      reduction in GH levels to less than 2 ng/mL (< 5 mU/L), as such GH concentrations
      are believed to be associated with normalization of long term survival. We sought
      to further define the nature of the cure in such patients, when cure has been
      achieved by alternative therapeutic modalities, in the expectation that
      hypothalamic neuroregulatory control of GH secretion might be affected
      differently by radiotherapy or surgery. In particular we wished to determine the
      effect of therapy modality on endogenous somatostatin (SMS) tone, using the GH
      response to i.v. arginine as a paradigm. We studied 20 patients with cured
      acromegaly (mean 24-h GH concentration, < 2 ng/mL). Eight patients had been cured
      by surgery only (S; 4 women and 4 men; mean +/- SEM age, 52 +/- 5 yr), and 12
      patients had been cured by radiotherapy (R; 4 women and 8 men; age, 52 +/- 3 yr).
      Sixteen healthy subjects were studied as a control group (C; 6 women and 10 men;
      age 53 +/- 3]. The median (range) GH during 24-h profiles was similar in each
      group: S, 1.3 (0.7-1.8) ng/mL; R, 0.6 (0.4-1.8) ng/mL; and C, 0.7 (0.4-3.2) ng/mL
      (P = 0.57). The median incremental GH responses to arginine were significantly
      lower in the R group compared with those in the S and C groups: S, 6.4 (2.1-16.6)
      ng/mL; R, 0.1 (0-1.7) ng/mL; and C, 9.2 (0-16.1) ng/mL (P = 0.0002; S vs. R, P <
      0.01; S vs. C, P > 0.05; R vs. C, P < 0.001). We conclude that in acromegalic
      patients deemed to be cured (GH, < 2 ng/mL), the mode of therapy has considerable
      influence on the remaining hypothalamic-somatotroph function. In view of the
      putative mechanism by which arginine releases GH, we suggest that radiotherapy
      leads to a reduction or complete loss of endogenous SMS tone. This may have
      implications for the treatment of those acromegalic patients who are not cured
      (GH, > 2 ng/mL) and who require SMS analog therapy.

PMID- 9589677
TI  - Increased bone resorbing activity of peripheral monocyte culture supernatants in
      elderly women.
AB  - Accelerated bone loss occurs in the years after menopause, and is an ongoing
      phenomenon in elderly women. The role of cytokines in bone loss after estrogen
      deficiency has been shown in ovariectomized rat and mice models. In humans, the
      involvement of bone resorbing cytokines is now well established. In the early
      years after menopause, monocyte activation leads to increased cytokine
      production. We have previously shown that the bone resorbing activity (BRA) of
      peripheral blood monocyte culture supernatants from postmenopausal women is
      higher than in premenopausal (Pre-M) women. This increased activity was related
      to interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha levels. We here
      investigate whether monocyte activation still occurs in older women and whether
      this relates to bone resorption. We studied 19 healthy Pre-M, and 24 early (E
      Post-M, menopause < 10 yr) and 24 late (L-Post-M, menopause > 10 yr)
      postmenopausal women. Peripheral blood monocytes were cultured for 48 h with 20%
      autologous plasma. BRA of monocyte supernatants (expressed as the ratio of
      monocyte supernatant over control bones supernatant) was assessed using fetal
      long-bone resorbing assays. Bone resorption was determined by urinary total
      pyridinoline excretion. BRA was significantly increased in E-Post-M and L-Post-M,
      compared with Pre-M subjects (1.20 +/- 0.10 and 1.15 +/- 0.20 vs. 0.73 +/- 0.10,
      respectively, both P < 0.05). Moreover, BRA of bones cultured with the
      supernatant of Pre-M was lower than BRA of control bones. BRA was significantly
      correlated with levels of IL-1, IL-6, and tumor necrosis factor-alpha in
      supernatant. Supernatant IL-1 levels were increased in E-Post-M, compared with
      Pre-M women (506 +/- 180 vs. 122 +/- 30, P < 0.05). Similarly, pyridinoline
      levels were increased in E-Post-M and L-Post-M, compared with Pre-M subjects (8.8
      +/- 1 and 10.5 +/- 0.9 vs. 5.8 +/- 0.5, respectively, both P < 0.05). BRA was
      significantly correlated to pyridinoline levels. These data indicate the presence
      of monocyte activation in L-Post-M, which may be responsible for the increased
      bone resorption and bone loss observed in this elderly population.

PMID- 9589678
TI  - Tetanus toxoid stimulation of the hypothalamic-pituitary-adrenal axis correlates
      inversely with the increase in tetanus toxoid antibody titers.
AB  - In humans, endotoxin activates the hypothalamic-pituitary-adrenal (HPA) axis, and
      the resulting increase in cortisol modulates the immune response. There is little
      information on the HPA axis response to other antigens. We examined the effect of
      the protein antigen tetanus toxoid on HPA axis activity in 10 healthy,
      premenopausal women (aged 28.6 +/- 2.6 yr). Subjects received im injections of
      placebo and tetanus toxoid at 1600 h on consecutive days. Blood samples for ACTH
      and cortisol were obtained every half-hour from--1 to 6 h and at 8, 12, and 16 h
      after each injection. Compared to placebo, tetanus toxoid administration
      stimulated significant increases in plasma ACTH and serum cortisol, with the
      maximum cortisol increase of 1.6-fold occurring 4.5 h after drug administration.
      Urinary free cortisol increased 1.8-fold in the 8 h after tetanus toxoid
      administration compared to that after placebo administration. Additionally, there
      was a significant inverse correlation (r = 0.87; P < 0.005) between the tetanus
      toxoid-induced increase in serum cortisol and the increase in tetanus antibody
      levels measured 1 month postvaccination. Thus, administration of the protein
      antigen tetanus toxoid activated the HPA axis in healthy, premenopausal women.
      This activation of the HPA axis correlated inversely with the antibody response
      to tetanus toxoid.

PMID- 9589679
TI  - Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygen
      mediated damage in relation to gestational age.
AB  - When maintaining first trimester placental villi in organ culture under
      conventional normoxic conditions, we have observed widespread degeneration of the
      syncytiotrophoblast within 24 h despite excellent viability for the
      cytotrophoblastic and stromal cell types. Here we identify loss of mitochondrial
      activity as an early event in this process. In the light of proposals that the
      early part of gestation occurs in a low oxygen environment and also reported
      associations between mitochondrial disruption and oxidative stress, we cultured
      first trimester villi under low oxygen conditions (2.5%). Mitochondrial
      superoxide dismutase (MnSOD) localization and activity at different gestational
      ages were also determined. It was found that syncytiotrophoblastic and
      mitochondrial morphology improved, and mitochondrial activity was retained for 6
      h and more if 8- to 10-week-old tissue was placed into a low oxygen environment
      immediately after removal from the uterus. The effect of oxygen concentration was
      less marked when using tissue of 14 weeks or more gestational age, which showed
      good survival and retention of mitochondrial activity under both low and ambient
      oxygen conditions. This correlated with our finding that placental MnSOD activity
      increased significantly between 8 and 14 weeks of gestation. Immunohistochemistry
      demonstrated that at 11 weeks; MnSOD was localized predominantly within the
      cytotrophoblast cells, whereas by 16 weeks it was found in the
      syncytiotrophoblast also. These results indicate an acute sensitivity of first
      trimester placenta syncytiotrophoblast to oxygen-mediated damage.

PMID- 9589680
TI  - Circadian rhythm of plasma leptin levels in upper and lower body obese women:
      influence of body fat distribution and weight loss.
AB  - Plasma leptin concentrations were measured every 20 min for 24 h in eight normal
      weight women and in eight upper body and eight lower body obese women matched for
      body mass index. The circadian rhythm of leptin, which could mathematically be
      described by a cosine, was characterized by an acrophase just after midnight in
      all subjects. The amplitude of a cosine fit as well as the average 24-h leptin
      concentration were increased by 280% and 420%, respectively, in obese compared to
      normal weight women. All characteristics of leptin concentration profiles were
      similar in upper body and lower body obese women, except for a significantly
      higher amplitude in the lower body obese group. Visceral and sc body fat depots
      were measured using magnetic resonance imaging in all three groups. Average 24-h
      leptin concentrations were strongly correlated with sc fat (r = 0.84), whereas
      visceral fat was not an independent predictor of the plasma leptin level. A loss
      of 50% of the overweight was associated with a 55% decrease in the average 24-h
      leptin concentrations in obese women (95% confidence interval, 12.3, 26.6),
      whereas the characteristics of the circadian rhythm of leptin remained unchanged.
      Finally, it was observed that a fasting plasma leptin concentration is not an
      acceptable indicator of the average leptin concentration over 24 h.

PMID- 9589681
TI  - Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding
      protein-2 are associated with malignancy in sporadic adrenocortical tumors.
AB  - In adrenocortical tumors, malignancy is strongly associated with insulin-like
      growth factor II (IGF-II) gene overexpression and abnormalities at the 11p15
      locus, suggesting a role for this growth factor in adrenocortical tumorigenesis.
      To further investigate this role, the IGF/IGF-binding protein (IGFBP) system was
      analyzed in 18 adrenocortical tumors, classified into 2 groups on the basis of
      their IGF-II messenger ribonucleic acid (mRNA) content (group 1, normal IGF-II
      mRNA content, mostly benign tumors; group 2, high IGF-II mRNA content, mostly
      malignant tumors). Group 2 tumors contained 10 times more IGF-II protein than
      group 1 tumors or normal adrenal tissue (P < 0.001), indicating efficient
      translation of IGF-II mRNA in malignant tumors. Western ligand blotting detected
      various functional IGFBPs in normal adrenocortical glands and tumors: a doublet
      of 39-42 kDa identified by immunoblotting as IGFBP-3, a band at 32 kDa, and bands
      at 29-30 and 24 kDa. Total IGFBP-3 protein levels were similar in the two groups
      of tumors. By contrast, malignant tumors differed from benign ones by specific
      expression of the 32-kDa IGFBP. Immunoblotting identified this 32-kDa band
      together with a proteolytic fragment of 25 kDa as IGFBP-2, and quantitative
      analysis showed significantly higher levels of total IGFBP-2 in malignant tumors
      than in benign tumors (P < 0.001). Despite enhanced levels of IGBP-2 protein in
      malignant tumors, no increase in IGFBP-2 mRNA levels was detected, suggesting
      post-transcriptional regulation of this IGFBP. These results confirm the major
      role of IGF-II in adrenocortical tumorigenesis and suggest that IGFBP-2 may be a
      regulator of IGF-II proliferative effects in this tumor system.

PMID- 9589683
TI  - Mid-follicular phase pulses of inhibin B are absent in polycystic ovarian
      syndrome and are initiated by successful laparoscopic ovarian diathermy: a
      possible mechanism regulating emergence of the dominant follicle.
AB  - The hypothalamic pulse generator of GnRH is recognized to be central to ovulatory
      function as evidenced by the anovulation of women with hypogonadotrophic
      hypogonadism due to Kallmann's syndrome or severe anorexia nervosa. LH is
      released from the anterior pituitary in pulses, the frequency of which is closely
      entrained with those of GnRH. In contrast, secretion of FSH is influenced by a
      number of regulatory molecules, including GnRH, estradiol, inhibin, and activin.
      The close temporal relationship between changes in levels of inhibin B and FSH in
      the mid-follicular phase suggests that the release of inhibin B by the
      preovulatory follicle critically regulates pituitary FSH secretion. Polycystic
      ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting
      ovulation, and abnormal ovarian morphology as detected by ultrasonography remains
      the most sensitive diagnostic marker for this disorder. The etiology of PCOS is
      unclear, but its effective treatment by both anti-estrogens and by exogenous FSH
      suggests that a primary disorder of FSH regulation may be central. To investigate
      the possible role of inhibin B in the pathology of PCOS, serum inhibin B levels
      were measured in 10 women with PCOS on cycle day 5 of a spontaneous or
      progestrogen-provoked bleed and compared with levels on cycle day 5 of 10 women
      with regular ovulatory cycles. The mean serum inhibin B levels in the PCOS
      patients were significantly higher at 248 (+/- 43.4) pg/mL compared with normal
      controls, 126 (+/- 18.6) pg/mL (P < 0.01). Ten women with clomiphene resistant
      PCOS and 5 normal controls consented to undergo serial blood sampling on cycle
      day 5. Time Series Analysis using a Fourier Transformation to analyze the power
      spectrum of the data revealed that in normal women there is a distinct
      periodicity in inhibin B levels with a clear peak detectable every 60-70 min (P <
      0.05), whereas in women with ovulatory dysfunction due to PCOS, no such pattern
      of regular pulsatility was seen. Four women with PCOS whose anovulation was
      successfully treated with laparoscopic ovarian diathermy (LOD) underwent repeat
      venous sampling following LOD. Their serum inhibin B levels fell to the upper
      limit of the normal range (160 +/- 38.5) pg/mL, and pulsatility was initiated. It
      is possible that inhibin B pulses are being generated directly by the ovary in
      response to pulses of GnRH in the peripheral circulation, or indirectly in
      response to FSH pulses arising in the pituitary. The function of inhibin B pulses
      in the mid-follicular phase of the normal cycle remains to be elucidated, but the
      absence of the normal pulsatile pattern in women with PCOS, in conjunction with
      high basal levels of inhibin B arising from the multiple small follicles
      characteristic of the PCOS ovary, appears to reinforce the development of a large
      cohort of small, developmentally arrested, and ultimately atretic follicles in
      these patients. Initiation of normal inhibin B pulsatility by LOD in patients
      with polycystic ovaries appears to correlate with the post-operative onset of
      ovular cycles.

PMID- 9589682
TI  - Cytokine-mediated regulation of 92-kilodalton type IV collagenase, tissue
      inhibitor or metalloproteinase-1 (TIMP-1), and TIMP-3 messenger ribonucleic acid
      expression in human endometrial stromal cells.
AB  - Interleukin-1 (IL-1) is expressed in human endometrium and has been shown to play
      an integral role in local cellular interactions during implantation. In addition,
      the matrix metalloproteinase (MMP) and its inhibitor, the tissue inhibitor of
      metalloproteinase (TIMP), are crucial during implantation, mediating in vitro
      trophoblast penetration, and are regulated by several cytokines expressed by
      trophoblast cells. We have investigated the roles of IL-1 beta and transforming
      growth factor-beta (TGF beta) in regulating TIMP-1, TIMP-3, and 92-kDa type IV
      collagenase messenger ribonucleic acid (mRNA) expression in human endometrial
      stromal cells using quantitative competitive PCR. Confluent stromal cell cultures
      treated with progesterone and estradiol for 9 days were stimulated with IL-1
      beta, IL-1 beta plus anti-IL-1 beta antibody, TGF beta, and TGF beta plus anti
      TGF beta antibody for an additional 24 h. Competitive complementary DNA fragments
      were constructed by deletion of a defined fragment from each of the target
      complementary DNA sequences and coamplified in quantitative competitive PCR as an
      internal standard. TIMP-1 and TIMP-3, but not 92-kDa type IV collagenase mRNA,
      were expressed in stromal cells. The 92-kDa type IV collagenase mRNA was only
      expressed after stimulation with IL-1 beta. IL-1 beta both augmented 92-kDa type
      IV collagenase mRNA expression and decreased TIMP-1 and TIMP-3 mRNA expression in
      a dose-dependent manner. Conversely, TGF beta augmented TIMP-1 and TIMP-3 mRNA
      expression, but did not affect 92-kDa type IV collagenase expression. IL-1 and
      TGF beta-mediated changes were both neutralized by specific antibodies. These
      results provide indirect evidence that IL-1 and TGF beta may play crucial roles
      at the embryo-maternal interface during trophoblast invasion by regulating
      stromal cell expression of TIMP-1, TIMP-3, and 92-kDa type IV collagenase, all of
      which are known to be important in trophoblast invasion.

PMID- 9589684
TI  - Fetal and maternal lipoprotein metabolism in human pregnancy complicated by type
      I diabetes mellitus.
AB  - Serum lipid, apolipoprotein concentration, and lipoprotein composition were
      determined in maternal and umbilical venous cord blood at delivery by elective
      Cesarean section (CS) in 10 singleton, full-term pregnancies with maternal
      insulin-dependent diabetes mellitus (type I DM), which predated pregnancy, and in
      22 nondiabetic pregnancies. The objectives of the study were to determine the
      influence of maternal type I DM, and hence potential fetal overnutrition on fetal
      lipid metabolism. There were no significant differences in gestational age, fetal
      weight, or fetal serum insulin concentration between the type I DM group and
      those with nondiabetic pregnancies, although fetal venous cord blood glucose was
      3.4 mmol/L (3.0-4.5 mmol/L) (median and 25th-75th percentiles) and 2.9 mmol/L
      (2.0-3.4 mmol/L), respectively, and maternal Hemoglobin A1c [9.6% (8.2-10.7%) and
      6.8% (6.3-7.8%), respectively], was significantly greater in the type I DM
      subjects (P < 0.02 and 0.002 respectively). Plasma nonesterified fatty acid
      (NEFA) concentrations were lower in the type I DM mothers [0.85 mmol/L (0.56-2.31
      mmol/L) compared with 1.14 mmol/L (0.88-1.24 mmol/L] in nondiabetic pregnancies;
      P < 0.0001). Serum high-density lipoprotein phospholipids (HDL-PL) were increased
      in type I DM mothers because of elevated HDL2 phospholipid [0.39 mmol/L (0.27
      0.48 mmol/L) compared with 0.12 mmol/L (0.06-0.21 mmol/L), respectively, P <
      0.01). The maternal HDL cholesterol (C) concentration was not significantly
      different in the uncomplicated and type I DM pregnancies. However, in the
      umbilical venous cord blood, serum levels of NEFA [0.49 mmol/L (0.33-1.29 mmol/L)
      in type I DM compared with 0.13 mmol/L (0.06-0.33 mmol/L) in nondiabetics; P <
      0.02)], total cholesterol (TC) [2.87 mmol/L (1.65-4.86 mmol/L) in type I DM
      compared with 1.65 mmol/L (1.46-1.87 mmol/L) in nondiabetics; P < 0.02]; free
      cholesterol (FC) [0.97 mmol/L (0.60-1.26 mmol/L) in type I DM compared with 0.62
      mmol/L (0.37-0.75 mmol/L) in nondiabetics; P < 0.05), and cholesteryl ester (CE)
      [1.90 mmol/L (1.44-3.33 mmol/L) in type I DM compared with 1.01 mmol/L (0.83-1.24
      mmol/L) in nondiabetics; P < 0.02), triglyceride (TG) (1.06 [0.50-1.91) mmol/L in
      type I DM compared with 0.29 [0.25-0.36] mmol/l in nondiabetics; P < 0.001),
      phospholipid (PL) (2.52 [1.73-3.03) mmol/L in type I DM compared with 1.34 [1.27
      1.48] mmol/L in nondiabetics; P < 0.01], and the apolipoproteins A-I and B had
      significantly higher concentrations in type I DM. In umbilical venous cord blood,
      ratios of HDL-TC and HDL-PL to apo AI, reflecting the lipid content of HDL, were
      reduced when the mother had type I DM during pregnancy (P < 0.02 and P < 0.0001,
      respectively). These results indicate that maternal type I DM may lead to a fetal
      serum lipoprotein composition more closely resembling that seen in the adult. In
      type I DM, maternal TG and PL and fetal TC, TG, PL, CE, and FC were correlated to
      NEFA levels (P < 0.05), but not to glucose, insulin secretion, or maternal
      control of type I DM. These data suggest that the enhanced supply of NEFA to the
      fetus in type I DM pregnancies may drive the synthesis of cholesterol as well as
      TGs and PLs.

PMID- 9589686
TI  - Analysis of human sodium iodide symporter gene expression in extrathyroidal
      tissues and cloning of its complementary deoxyribonucleic acids from salivary
      gland, mammary gland, and gastric mucosa.
AB  - The ability to concentrate iodide is a fundamental property of normally
      functioning thyroid tissue and represents the first step in the production of
      thyroid hormones. Iodide uptake has been demonstrated in various extrathyroidal
      tissues, including salivary gland, gastric mucosa, and lactating mammary gland.
      Recently, cloning and molecular characterization of the human sodium iodide
      symporter (hNIS) have been reported; however, the patterns of hNIS gene
      expression in human tissues have remained unidentified. To examine the profiles
      of human hNIS gene expression in various normal human tissues, we performed high
      stringency Northern blot analysis using a 32P-labeled hNIS-specific complementary
      DNA (cDNA) probe (nucleotides 1184-1667). To detect rare hNIS transcripts in
      small tissue samples, RT-PCR was performed with a pair of hNIS-specific
      oligonucleotide primers designed to amplify a portion (nucleotides 1184-1667) of
      the hNIS gene. hNIS-specific transcripts were confirmed by Southern hybridization
      using a digoxigenin-labeled internal hNIS-specific oligonucleotide probe
      (nucleotides 1460-1477). To monitor cDNA integrity and quantity, and to rule out
      DNA contamination and illegitimate transcription, all samples were coamplified
      with two pairs of intron-spanning primers designed to amplify fragments of the
      human beta-actin and thyroglobulin genes, respectively. Using Northern blot
      analysis, hNIS transcripts of approximately 4 kb were detected in thyroid gland
      and parotid gland but not in a broad range of endocrine and nonendocrine tissues.
      RT-PCR and Southern hybridization revealed hNIS gene expression in thyroid gland,
      salivary gland, parotid gland, submandibular gland, pituitary gland, pancreas,
      testis, mammary gland, gastric mucosa, prostate and ovary, adrenal gland, heart,
      thymus, and lung. By contrast, hNIS transcripts were not detected in normal
      orbital fibroblasts, colon, and nasopharyngeal mucosa. To further analyze hNIS
      gene sequences in parotid gland, mammary gland, and gastric mucosa, the EXPAND
      High Fidelity PCR System and three sets of overlapping NIS oligonucleotide
      primers were used for amplification and cloning. The resulting PCR products were
      subcloned into pBluescript-SKII(-)vector, and at least two independent cDNA
      clones derived from each tissue were subjected to automated sequencing. The
      nucleotide sequences of hNIS cDNA derived from parotid gland, mammary gland, and
      gastric mucosa revealed full identity with the recently published human thyroid
      derived NIS cDNA sequence. In conclusion, our results demonstrate markedly
      variable levels of hNIS gene expression in several extrathyroidal tissues.
      Although the physiological role of hNIS in these tissues awaits further study,
      our results suggest that the capacity to actively transport iodine may be a
      feature common to several secretory and endocrine tissues. The diminished
      capacity to transport and concentrate iodide in extrathyroidal tissues (such as
      parotid gland, mammary gland, and gastric mucosa), compared with thyroid gland,
      does not seem to be caused by an altered primary structure of the hNIS cDNA.
      Variability of NIS gene expression levels in normal extrathyroidal tissues may
      rather be caused by differences in NIS gene transcriptional activity. Further
      studies will address this hypothesis and examine the mechanisms of tissue
      specific regulation of NIS gene expression.

PMID- 9589685
TI  - Involvement of ovarian steroids in the opioid-mediated reduction of insulin
      secretion in hyperinsulinemic patients with polycystic ovary syndrome.
AB  - To evaluate the possible involvement of ovarian steroids on the opioid-mediated
      disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we
      studied 40 PCOS women. All patients underwent an oral glucose tolerance test
      (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26
      women were classified as hyperinsulinemic and continued the study protocol.
      Patients were randomly divided into three groups characterized by different
      treatments: group A (nine patients) was treated with GnRH analog (one ampule
      every 28 days for 2 months), group B (eight patients) was treated with naltrexone
      (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine
      patients) was treated with GnRH analog plus naltrexone for 2 months. After
      continuation of treatment, all patients repeated the basal study in a second
      hospitalization. Naltrexone treatment significantly reduced the insulin response
      to OGTT, whereas GnRH analogue administration did not significantly change the
      insulin secretion after the glucose load. The GnRH analog/ naltrexone cotreatment
      was not able to influence the insulin secretory pattern; in fact, the insulin
      area under the curve was superimposable before and after therapy. These data
      could lead to the hypothesis that the opioidergic regulation of insulin secretion
      requires a normal steroidogenic pattern, thus suggesting that ovarian steroids
      modulate opioid activity also at peripheric districts.

PMID- 9589687
TI  - Increased oxidizability of low-density lipoproteins in hypothyroidism.
AB  - Hypothyroidism leads to an increase of plasma low-density lipoprotein (LDL)
      cholesterol levels. Oxidation of LDL particles changes their intrinsic
      properties, thereby enhancing the development of atherosclerosis. T4 has three
      specific binding sites on apolipoprotein B; furthermore it inhibits LDL oxidation
      in vitro. We therefore hypothesized that T4 deficiency not only results in
      elevated LDL-cholesterol levels but also in increased LDL oxidation. Ten patients
      with overt hypothyroidism were studied when untreated (TSH 76 +/- 13 mU/L, T4 40
      +/- 6 nmol/L) and again when they were euthyroid for at least 3 months during T4
      treatment (TSH 2.7 +/- 0.5 mU/L, T4 115 +/- 11 nmol/L). Plasma lipids and
      lipoproteins and the oxidizability and chemical composition of LDL were
      determined. The transition from the hypothyroid to the euthyroid state was
      associated with a decrease (mean +/- SE) of plasma total cholesterol (5.8 +/- 0.3
      vs. 4.8 +/- 0.2 mmol/L, P < 0.005), LDL cholesterol (3.8 +/- 0.3 vs. 2.9 +/- 0.2
      nmol/L, P < 0.005) and apolipoprotein B (1.2 +/- 0.1 vs. 0.9 +/- 0.1 g/L, P <
      0.005); plasma high-density lipoprotein cholesterol, apolipoprotein A-1, and
      triglycerides did not change. The actual content of dienes in LDL particles was
      increased in hypothyroidism, with a decrease after T4 suppletion [median (range)
      = 257 (165-346) vs. 188 (138-254) nmol/mg LDL protein, P < 0.005; reference range
      140-180]. The lag time, an estimate of the resistance of LDL against oxidation in
      vitro, was shortened when hypothyroid but normalized after T4 treatment [29 (19
      90) vs. 77 (42-96) min, P < 0.005; reference range 67-87]. The density, the
      relative fatty acid content, and the vitamin E content of LDL particles did not
      change. In conclusion, the hypothyroid state is not only associated with a
      quantitative increase of LDL particles, but it also changes their quality by
      increasing LDL oxidizability.

PMID- 9589688
TI  - Sex differences in endocrine and psychological responses to psychosocial stress
      in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone
      treatment.
AB  - Evidence from animal as well as human studies has suggested that significant sex
      differences exist in hypothalamus-pituitary-adrenal axis (HPA) activity. As
      gonadal steroids could be important modulators of HPA sex differences, stress
      responses were investigated in subjects of advanced age after
      dehydroepiandrosterone (DHEA) or placebo treatment. After a 2-week treatment with
      50 mg DHEA daily or placebo, 75 men and women (mean age, 67.6 yr) were exposed to
      the Trier Social Stress Test (TSST). The TSST is a brief psychosocial stress that
      consists of a free speech and mental arithmetic task in front of an audience. The
      results show that the TSST induced significant increases in ACTH, salivary free
      cortisol, total plasma cortisol, norepinephrine, and heart rates (all P < 0.0001)
      as well as decreased positive affect in the elderly (P = 0.0009). Men showed
      larger stress responses in ACTH (P = 0.004), salivary free cortisol (P = 0.044),
      and plasma total cortisol (P = 0.076) compared to women. No sex differences were
      observed in norepinephrine, epinephrine, or heart rate responses. In contrast to
      ACTH and cortisol response differences, women reported that they were
      significantly more stressed by the TSST than men (P = 0.0051). Women treated with
      DHEA showed ACTH stress responses similar to those of men, but significantly
      enhanced compared to those of women taking placebos (P < 0.009). No other stress
      response differences emerged between DHEA and placebo groups. Finally, DHEA
      treatment did not result in an improvement of subjective well-being. We conclude
      that elderly men show larger HPA responses than women to psychosocial stress, as
      studied in the TSST. Estrogen effects on hypothalamic CRF-producing neurons might
      be responsible for these sex differences.

PMID- 9589689
TI  - Congenital central hypothyroidism due to a homozygous mutation in the thyrotropin
      beta-subunit gene follows an autosomal recessive inheritance.
AB  - A 5-month-old infant of nonconsanguineous parents had severe hypothyroidism.
      Undetectable serum levels of T3 and T4 in combination with an undetectable
      baseline TSH level led to the diagnosis of central hypothyroidism. Administration
      of TRH failed to increase serum TSH, but not PRL, confirming isolated TSH
      deficiency. Measurement of the TSH in serum with three different immunoassays
      that recognize different epitopes of the TSH molecule failed to detect TSH,
      suggesting an aberrant or absent TSH. Direct sequencing of the entire coding
      region of the human TSH beta-subunit gene revealed a homozygous single base pair
      deletion in codon 105, resulting in a frame shift with a premature stop at codon
      114. The truncated TSH beta peptide lacks the terminal five amino acids.
      Furthermore, the cysteine in codon 105 that is believed to be important for the
      interaction of the TSH beta-subunit with the alpha-subunit, is replaced with a
      valine (C105V), supporting the theory of a conformational change in the TSH
      molecule. Genotyping confirmed that the proposita was homozygous for this
      mutation, whereas her unaffected parents, the paternal grand-mother, and the
      maternal grandfather were heterozygous. Thus, isolated TSH deficiency follows an
      autosomal recessive mode of inheritance in this kindred.

PMID- 9589690
TI  - Novel chromosomal abnormalities identified by comparative genomic hybridization
      in parathyroid adenomas.
AB  - The molecular basis of parathyroid adenomatosis includes defects in the cyclin
      D1/PRAD1 and MEN1 genes but is, in large part, unknown. To identify new locations
      of parathyroid oncogenes or tumor suppressor genes, and to further establish the
      importance of DNA losses described by molecular allelotyping, we performed
      comparative genomic hybridization (CGH) on a panel of 53 typical sporadic
      (nonfamilial) parathyroid adenomas. CGH is a new molecular cytogenetic technique
      in which the entire tumor genome is screened for chromosomal gains and/or losses.
      Two abnormalities, not previously described, were found recurrently: gain of
      chromosome 16p (6 of 53 tumors, or 11%) and gain of chromosome 19p (5 of 53, or
      9%). Losses were found frequently on 11p (14 of 53, or 26%), as well as 11q (18
      of 53, or 34%). Recurrent losses were also seen on chromosomes 1p, 1q, 6q, 9p,
      9q, 13q, and 15q, with frequencies ranging from 8-19%. Twenty-four of the 53
      adenomas were also extensively analyzed with polymorphic microsatellite markers
      for allelic losses, either in this study (11 cases) or previously (13 cases).
      Molecular allelotyping results were highly concordant with CGH results in these
      tumors (concordance level of 97.5% for all informative markers/chromosome arms
      examined). In conclusion, CGH has identified the first two known chromosomal gain
      defects in parathyroid adenomas, suggesting the existence of direct-acting
      parathyroid oncogenes on chromosomes 16 and 19. CGH has confirmed the locations
      of putative parathyroid tumor suppressor genes, also defined by molecular
      allelotyping, on chromosomes 1p, 6q, 9p, 11q, 13q, and 15q. Finally, CGH has
      provided new evidence favoring the possibility that distinct parathyroid tumor
      suppressors exist on 1p and 1q, and has raised the possibility of a parathyroid
      tumor suppressor gene on 11p, distinct from the MEN1 gene on 11q. CGH can
      identify recurrent genetic abnormalities in hyperparathyroidism, especially
      chromosomal gains, that other methods to not detect.

PMID- 9589691
TI  - Apparent congenital athyreosis contrasting with normal plasma thyroglobulin
      levels and associated with inactivating mutations in the thyrotropin receptor
      gene: are athyreosis and ectopic thyroid distinct entities?
AB  - Loss-of-function mutations in the TSH receptor gene (TSH-R), usually leading to
      asymptomatic hyperthyrotropinemia, have been reported since 1995 in a total of
      eight pedigrees, with a pattern of transmission suggesting autosomal recessive
      inheritance. Although normal TSH secretion and action are not necessary for
      normal migration of the thyroid analage, they are essential for normal thyroid
      growth and function. In keeping with this concept, we report a severely
      hypothyroid boy with a normally located but very hypoplastic and hypofunctional
      thyroid caused by TSH-R loss-of-function mutations. The propositus' maternal
      great aunt also had apparent athyreosis. The propositus had undetectable uptake
      on 99mpertechnetate scintigraphy but normal plasma thyroglobulin at 15 days of
      age. He was found to be a compound heterozygote for TSH-R mutations, with the
      maternal allele carrying a splicing mutation (G to C transversion at position +3
      of the donor site of intron 6) and the other allele a deletion of two nucleotides
      (2 bases of codon 655 in exon 10). The great aunt's TSH-R was normal. We also
      report the sex ratio of hypothyroid newborns referred to our center since 1989
      with apparent athyreosis (5 girls, 7 boys) and with ectopic thyroid tissue (41
      girls, 15 boys). We conclude that different genetic and nongenetic mechanisms for
      athyreosis and ectopic thyroid are likely, and that these two distinct entities
      are themselves heterogeneous. Our results further show that inactivating
      mutations in TSH-R may account for some cases of apparent congenital athyreosis
      and should be suspected, especially if plasma thyroglobulin levels are normal.

PMID- 9589692
TI  - Luteinizing hormone and human chorionic gonadotropin decrease type 2 5 alpha
      reductase and androgen receptor protein levels in women's skin.
AB  - The present study tested the hypothesis that LH/hCG may regulate the type 2 5
      alpha-reductase and androgen receptor protein levels in skin. The skin samples
      obtained from women undergoing abdominal laparotomy or abdominoplasty were
      incubated in the presence or absence of hCG. Western blotting was then performed
      to determine the response of type 2 5 alpha-reductase and androgen receptors. The
      results demonstrated that treatment with hCG resulted in a significant time- and
      dose-dependent, although modest, decrease in 5 alpha-reductase and androgen
      receptor levels compared to the controls. These effects were mimicked by LH, but
      not by other hormones in the glycoprotein hormone family, including alpha- and
      beta-subunits of hCG. Although the biological and clinical importance of this
      regulation remains to be determined, these findings reaffirm that human skin is
      among the nongonadal tissues that respond to LH and hCG treatment.

PMID- 9589693
TI  - Interleukin-8 in the human endometrium.
AB  - We have previously shown that interleukin-8 (IL-8), a cytokine with neutrophil
      chemotactic/activating and T cell chemotactic activity, is produced by human
      endometrial stromal and glandular cells in culture. The present study
      investigated the temporal and spatial expression of IL-8 messenger ribonucleic
      acid (mRNA) and protein in the human endometrium. Endometrial tissue (n = 52) was
      obtained from human uteri after hysterectomy conducted for reasons other than
      endometrial disease or from endometrial biopsies. The day of the menstrual cycle
      was established from women's menstrual history and was confirmed by histology.
      Half of the tissues (n = 26) were snap-frozen in liquid nitrogen, cellular RNA
      was extracted, and Northern blots were hybridized with a riboprobe complementary
      to a specific sequence of IL-8 mRNA. The remaining tissues (n = 26) were
      processed for frozen sections, and immunohistochemistry was performed using mouse
      antihuman IL-8 antibody. Comparison of IL-8 mRNA levels throughout the menstrual
      cycle revealed that late secretory and early to midproliferative phase IL-8
      expression was significantly greater than midcycle expression (P < 0.02).
      Analysis of the IL-8 immunohistochemistry revealed that IL-8 protein is found in
      the surface epithelium and glands throughout the menstrual cycle. There was no
      detectable immunoreactive IL-8 in the stromal cells. We conclude that IL-8 is
      produced in the human endometrium in vivo, and the variations of IL-8 mRNA
      throughout the menstrual cycle suggest that sex hormones may regulate its gene
      expression. We speculate that IL-8 may modulate the timely recruitment of
      neutrophils and lymphocytes into the endometrium.

PMID- 9589694
TI  - Cellular localization of c-jun messenger ribonucleic acid and protein and their
      relation to the proliferation marker Ki-67 in the human endometrium.
AB  - We studied cellular c-jun messenger RNA (mRNA) expression in the human
      endometrium during the menstrual cycle (n = 47) and in human decidua during
      pregnancy (n = 8), by using digoxigenin-labeled RNA probes in in situ
      hybridization. The same tissue samples were also analyzed for c-Jun protein and
      the proliferation marker Ki-67. In the proliferative endometrium, strong
      expression of c-jun was detected in luminal and glandular epithelium as well as
      in fibroblast-like stromal cells. During the early luteal phase, strong
      hybridization signals were identified in both epithelial and stromal
      compartments, with the strongest hybridization in the stromal cells beneath the
      epithelium. c-jun mRNA was markedly diminished in luminal and glandular epithelia
      of mid- and late secretory phase endometria, but it remained unchanged in the
      stroma. Regardless of the phase of the menstrual cycle, significant hybridization
      was identified in endothelial cells in the endometrium and myometrium, and a low
      signal was detected in myometrial muscle cells as well. During early gestation,
      weak expression of c-jun mRNA was observed in glandular epithelial cells and in
      decidualized stromal cells. In term pregnancy decidua, only low-level
      hybridization was detected in a few decidual cells. Nuclear immunostaining of c
      Jun was detected in luminal and glandular epithelia and in stroma throughout the
      menstrual cycle. The location of Ki-67 antigen was temporally related to the c
      jun mRNA expression in cycling endometrium and pregnancy decidua. From our data
      we conclude that 1) c-jun mRNA is differentially expressed in endometrial
      epithelial and stromal cells; 2) c-jun mRNA is cyclically regulated in the human
      endometrial epithelium; 3) c-jun mRNA expression is temporally related to
      epithelial proliferation in the endometrium; and 4) c-Jun protein is present in
      the human endometrium throughout the menstrual cycle.

PMID- 9589695
TI  - Molecular basis of severe gynecomastia associated with aromatase expression in a
      fibrolamellar hepatocellular carcinoma.
AB  - This report represents the first study in the literature linking development of
      severe gynecomastia, in a 17 1/2-yr-old boy, to high levels of aromatase
      expression in a large fibrolamellar hepatocellular carcinoma, which gave rise to
      extremely elevated serum levels of estrone (1200 pg/mL) and estradiol-17 beta
      (312 pg/mL) that suppressed FSH and LH (1.3 and 2.8 IU/L, respectively), and
      consequently testosterone (1.53 ng/mL). After removal of a 1.5-kg hepatocellular
      carcinoma, gynecomastia partially regressed, and essentially, normal hormone
      levels were restored (estradiol-17 beta, < 50 pg/mL; estrone, 74 pg/mL;
      testosterone, 6.85 ng/mL; and FSH/LH, 6.3/3.7 mIU/mL). Conversion of C19 steroids
      to estrogens occurs in a number of human tissues and is catalyzed by aromatase
      P450 (P450arom), the product of the CYP19 gene in a number of human tissues.
      Tissue-specific promoters are used to regulate P450arom gene transcription in
      adult human tissues, e.g. promoters I.4 and I.3 in adipose fibroblasts, and
      promoter II in the gonads. Human fetal liver uses promoter I.4 to express
      markedly high levels of P450arom, whereas hepatic P450arom expression normally
      becomes undetectable in postnatal life. Using immunohistochemistry, diffuse
      intracytoplasmic aromatase expression was detected in the liver cancer cells from
      this severely feminized boy. Northern analysis indicated the presence of P450arom
      transcripts in total RNA from the hepatocellular cancer but not in the adjacent
      liver nor in disease-free adult liver samples. Promoter use for aromatase
      expression was determined by a specific RT-PCR method. Promoters I.3 and II were
      used for P450arom gene expression in the hepatocellular cancer tissue. Because
      aromatase is not expressed in the disease-free adult liver, the presence of
      extremely high levels of aromatase expression in this fibrolamellar
      hepatocellular carcinoma tissue is intriguing, particularly because there is
      preferential use of the proximally located P450arom promoters I.3 and II by the
      tumor, instead of the much more distally located fetal liver-type promoter I.4.

PMID- 9589696
TI  - Comparative genomic hybridization analysis of nonfunctioning pituitary tumors.
AB  - Clinically nonfunctioning pituitary adenomas constitute about one third of
      pituitary neoplasms and are considered monoclonal tumors. The molecular
      mechanisms of tumorigenesis in these neoplasms are poorly understood, as
      evidenced by the paucity of reported somatic genetic alterations. Furthermore,
      the somatic mutations detected to date were primarily ascribed to candidate genes
      or chromosomal regions: gsp, ras, p53 mutations, and allelic losses of 11q and
      13q. To gain insight into which chromosomal regions bear genes involved in
      nonfunctioning pituitary tumorigenesis, we examined 23 such tumors by comparative
      genomic hybridization. Four tumors showed no genetic abnormality, and the rest
      (17 of 23, 74%) exhibited at least one chromosomal region of abnormality. Gains
      and losses affected all chromosomes (except for chromosome 14). Notably, 8 of 23
      tumors (34.7%) displayed sex chromosome and chromosome 18 aberrations
      (amplifications or deletions). Nonrandom DNA amplification of sub-chromosomal
      regions on 4q, 5q (5q13-->5q23), 9p (9p21-->9pter), 13q (13q21-->13q32), and 17q
      were detected in 10-30% of the tumors. Noteworthy, no tumor displayed deletion of
      11q, the MEN1 gene locus. These findings suggest that genes localized to
      previously undescribed chromosomal regions play a role in the tumorigenesis of
      nonfunctioning pituitary adenomas.

PMID- 9589697
TI  - Obesity and gender influence cortisol secretion and metabolism in man.
AB  - In obesity, urinary cortisol excretion is enhanced but plasma cortisol levels are
      not elevated, suggesting that metabolic clearance of cortisol is increased.
      Cortisol is metabolised in liver and fat by A-ring reductases but also
      regenerated from inactive cortisone in liver, fat, and skeletal muscle by 11 beta
      reductase. These enzymes are regulated by estrogen. This study addressed whether
      there are differences in cortisol metabolism in obesity, and whether these
      differences are estrogen dependent. 31 men and 37 post-menopausal women (9 on
      estrogen replacement therapy) aged 47-53 y supplied 24 h urine for gas
      chromatography/mass spectrometry. Total cortisol metabolite excretion was higher
      in men than women, but weakly related to indices of obesity. By contrast,
      metabolism of cortisol favoured 5 alpha-rather than 5 beta-reduction in obese men
      and obese women, and favoured cortisol rather than cortisone in obese men. In
      women compared with men ratios of 5 alpha-/5 beta-reduced and cortisol/cortisone
      metabolites were also higher but these variables were not affected by estrogen
      replacement therapy. We conclude that in obesity, inactivation of cortisol by 5
      alpha-reductase is enhanced but this is offset by impaired metabolism of cortisol
      by 5 beta-reductase in women and enhanced conversion of cortisone to cortisol by
      11 beta-reductase in men. These observations suggest that cortisol clearance is
      altered in obesity, and this may account for activation of the hypothalamic
      pituitary-adrenal axis. Moreover, these data predict that obese subjects will
      have higher concentrations of cortisol in key target tissues including liver and
      visceral fat. This may contribute to the adverse metabolic consequences of
      obesity.

PMID- 9589698
TI  - Leptin expression in human mammary epithelial cells and breast milk.
AB  - Leptin has recently been shown to be produced by the human placenta and
      potentially plays a role in fetal and neonatal growth. Many functions of the
      placenta are replaced by the mammary gland in terms of providing critical growth
      factors for the newborn. In this study, we show that leptin is produced by human
      mammary epithelial cells as revealed by RT/PCR analysis of total RNA from mammary
      gland and immunohistochemical staining of breast tissue, cultured mammary
      epithelial cells, and secretory epithelial cells present in human milk. We also
      verify that immunoreactive leptin is present in whole milk at 30- to 150-fold
      higher concentrations than skim milk. We propose that leptin is secreted by
      mammary epithelial cells in milk fat globules, which partition into the lipid
      portion of breast milk.

PMID- 9589699
TI  - A new polymorphic restriction site in the human 11 beta-hydroxysteroid
      dehydrogenase type 2 gene.
AB  - The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2)
      inactivates glucocorticoids in the kidney and thus prevents glucocorticoids from
      occupying the non-selective mineralocorticoid receptor in epithelial tissues.
      Mutations in the HSD11B2 gene have been found to cause the syndrome of apparent
      mineralocorticoid excess, a rare autosomal recessive disease characterized by
      severe hypertension. Thus, this locus could also be an ideal candidate involved
      in the etiology of primary hypertension. We identified a polymorphism in exon 3
      characterized by a GAG to GAA transition at codon 178, with the loss of an Alu I
      restriction site and analysed it in an association study using end-stage renal
      disease patients, diabetic or essential hypertensive patients and control
      subjects. Two-hundred and eighty nine subjects and patients were analysed; the
      genotype was determined by amplification of genomic DNA and subsequent digestion
      with Alu I restriction enzyme. The prevalence of the Alu I allele was 8.6% in
      healthy control subjects (n = 116). This prevalence was lower (chi 2 P = 0.035
      vs. controls) than the 18.0% in a group of renal transplant patients (n = 61).
      The corresponding values for patients with diabetes mellitus (n = 25),
      hypertension (n = 41) and patients on dialysis (n = 46) were 4.0%, 4.8% and 4.3%,
      respectively. There was no correlation between blood pressure and the marker in
      non-ESRD subjects. These data indicate the presence of a polymorphic marker in
      exon 3 of the HSD11B2 gene; this marker is associated with end-stage renal
      disease but not with essential hypertension in humans.

PMID- 9589700
TI  - Potent inhibitory effect of troglitazone on carotid arterial wall thickness in
      type 2 diabetes.
AB  - There is increasing evidence that insulin resistance may be causally related to
      atherosclerosis. The measurement of common carotid arterial intimal and medial
      complex thickness (IMT) by B-mode ultrasound technique has been recognized as a
      powerful and non-invasive method to evaluate early atherosclerotic lesions. We
      investigated the effect of treatment with troglitazone, an insulin sensitizer, on
      IMT in a total of 135 Japanese subjects with type 2 diabetes. Troglitazone (400
      mg daily) was administered for 6 months in 57 patients. Compared to control group
      (n = 78), the group given troglitazone showed a significant decrease in IMT as
      early as 3 months after the administration (IMT change: -0.080[SE 0.016] mm vs.
      control 0.027[SE 0.007] mm, P < 0.001). The decrease in IMT was also found after
      6 months, although further decrease was not observed. Both HbA1c and postprandial
      serum triglycerides were decreased after troglitazone, but there was no
      statistically significant relation between a decrease in IMT and those in HbA1c
      or postprandial triglycerides. These findings indicate that troglitazone has a
      potent inhibitory effect on progression of early atherosclerotic lesions probably
      through the decreased insulin resistance in type 2 diabetes.

PMID- 9589701
TI  - The effects of glucocorticoids on leptin levels in humans may be restricted to
      acute pharmacologic dosing.

PMID- 9589702
TI  - Commentary to the article--low levels of sex hormone-binding globulin and
      testosterone are associated with smaller, denser low density lipoproteins in
      normoglycemic men.

PMID- 9589703
TI  - Muscle dysfunction in subclinical hypothyroidism.

PMID- 9589704
TI  - Thrombopoiesis is increased in hyperthyroidism.

PMID- 9589705
TI  - Nitric oxide synthetase distribution in the sclerocorneal trabecular meshwork in
      chronic simple glaucoma patients.

PMID- 9589706
TI  - Ocular angiogenesis; a new in vivo experimental model.

PMID- 9589708
TI  - Monolateral pseudoexfoliatio capsulae: a study of choroidal blood flow.

PMID- 9589707
TI  - Color Doppler imaging and plasma levels of endothelin-1 in low-tension glaucoma.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular
      endothelin cells There are reports in the literature that ET-1 plasma levels are
      raised in low tension glaucoma (LTG). ET-1 plasma concentration and Color Doppler
      Imaging (CDI) evaluation in ophthalmic and posterior ciliary arteries were
      measured in 15 LTG patients and in 15 healthy subjects. The blood flow index
      recorded for the ophthalmic artery in normal subjects was a PSV of 36.646 +/-
      6.611 cm/sec with RI of 0.717 +/- 0.019 while in the LTG patients it was 32.961
      +/- 3.045 cm/sec (p < 0.003) with RI of 0.789 +/- 0.018 (p < 0.001). For the
      posterior ciliary arteries in the same two groups, we obtained a PSV of 13.878 +/
      4.149 cm/sec vs 8.720 +/- 1.645 cm/sec (p < 0.001) and an RI of 0.679 +/- 0.039
      vs 0.722 +/- 0.024 (p < 0.001). The plasma ET-1 level in normal subjects was
      1.720 +/- 0.174 pg while in LTG patients it was 2.947 +/- 0.217 pg (p < 0.001).
      On the basis of our experience, we think that GON and the visual field damage
      found in LTG can be attributed to an alteration in the endothelial self
      regulating sections and consequent vascular insufficiency, particularly
      pronounced in the posterior ciliary arteries which, since it is these that
      provide the blood supply to the optic nerve head, leads to irreversible
      functional damage.

PMID- 9589709
TI  - Relationship between cephaloophthalmic haemodynamics and ocular functions in
      patients affected by carotid stenosis: preliminary results.

PMID- 9589710
TI  - Evaluation of the clinical course of central retinal vein occlusion in eyes with
      and without glaucoma.

PMID- 9589711
TI  - Normal tension glaucoma: a ten-year follow-up.
AB  - The authors describe the results obtained in 10 years of observation of a group
      of 41 eyes affected by normal tension glaucoma. An evolution of perimetric
      defects was found in 29.26% of the eyes examined.

PMID- 9589712
TI  - Pressure-reducing efficacy and tolerability of betaxolol in ionic solution.

PMID- 9589713
TI  - Short-term clinical trial evaluating the efficacy of the combination of
      apraclonidine 0.5% solution and betaxolol 0.25% suspension.

PMID- 9589714
TI  - Hypotensive effects of dorzolamide eyewash in maximal therapy glaucoma patients:
      a comparative study with oral acetazolamide.

PMID- 9589715
TI  - 2% dorzolamide and cornea: an ultrabiomicroscopic study.

PMID- 9589716
TI  - Ocular hypotensive effect of ketanserin in patients with primary open angle
      glaucoma.

PMID- 9589717
TI  - Effects of adrenergics, adrenolytics, cholinergics and carbonic anhydrase
      inhibitors on ibopamine-induced ocular hypertension in POAG.

PMID- 9589718
TI  - The use of a standardized exercise as a provocative test in pigmentary dispersion
      syndrome.

PMID- 9589719
TI  - Ultrasound biomicroscopy study of ciliary body and its influence on anterior
      chamber angle width.

PMID- 9589720
TI  - Estimating glaucomatous anatomical damage by computerized automated perimetry.
AB  - The ability of two methods (the Glaucoma Staging System and the Functional Score
      index) in estimating anatomical damage from automated visual field data was
      studied in 100 patients with chronic open-angle glaucoma. The level of
      association between functional and anatomical loss (classified by cup/disk ratio
      assessment) was satisfactory in both systems. Both the GSS (Glaucoma Staging
      System) and the FS (Functional Score) could be useful for estimating and
      quantifying the glaucomatous anatomical damage, both in the day-to-day clinical
      practice and in research.

PMID- 9589721
TI  - Perimetric findings in subjects with elevated myopia and glaucoma.

PMID- 9589723
TI  - The slope of the regression lines of focal RA/DA cumulative curves can be an
      indicator of early glaucomatous changes.

PMID- 9589722
TI  - Delayed postretinal neural conduction in glaucoma patients: correlations between
      electrophysiological and computerized static perimetry parameters.

PMID- 9589724
TI  - Diagnostic and prognostic indices in primary open angle glaucoma: a color Doppler
      study.
AB  - The authors compute a diagnostic (Di) and a prognostic (Pi) index in primary open
      angle glaucoma. Four groups of patients were studied. Group A consisted of
      subjects under 50 years of age, group B of subjects over 50 years of age, group C
      of patients with normal tension glaucoma and group D with high tension glaucoma.
      All patients underwent color doppler imaging of the ophthalmic, posterior ciliary
      and choroid arteries. The Di of the choroid vessels were 0.967 +/- 0.011 (gp. A),
      1.112 +/- 0.010 (gp. B), 1.506 +/- 0.008 (gp. C) and 2.891 +/- 0.083 (gp. D). The
      Pi of the posterior ciliary arteries were 22.700 +/- 1.160 (gp. A), 20.000 +/-
      0.943 (gp. B), 15.100 +/- 0.568 (gp. C) and 12.100 +/- 0.083 (gp. D).
      Confirmation of these data might validate them as a tool for preventing the
      evolution of glaucomatous optic neuropathy.

PMID- 9589725
TI  - Ocular haemodynamics in some subgroups of normal pressure glaucoma.
AB  - The authors studied, by means of Color Doppler Imaging, a group of Normal
      Pressure Glaucoma subjects They found some haemodynamic abnormalities in them
      which differed in the various subgroups. It would seem that, for each NPG
      subgroup, there are specific physiopathological and clinical features.

PMID- 9589726
TI  - Trans-scleral krypton laser cyclophotocoagulation: our experience of its use on
      patients with neovascular glaucoma.
AB  - Trans-scleral cyclophotocoagulation is an efficacious method in neovascular
      glaucoma (NVG) treatment. We have used it with krypton laser on 12 eyes of 12
      patients affected by NVG with algetic symptoms. Six months after treatment,
      intraocular pressure was down enough for the pain to disappear. Executional
      simplicity and the possibility of modulating the intensity of the treatment are
      grounds for the encouragement of the technique's use in NVG.

PMID- 9589727
TI  - Diode laser trans-scleral cyclophotocoagulation in refractory glaucoma treatment.

PMID- 9589728
TI  - Temporal corneal phacoemulsification combined with separate-incision superior
      trabeculectomy vs standard phacotrabeculectomy. A comparative study.
AB  - The aim of the study was to compare functional and refractive outcome after
      temporal approach phacoemulsification combined with superior trabeculectomy
      against that of standard superior phacotrabeculectomy in patients affected by
      cataract and uncontrolled glaucoma. Fifty patients undergoing combined surgery
      were randomly allocated to receive either a standard superior phacotrabeculectomy
      (group A) or a temporal via clear cornea phacoemulsification combined with a
      separate superior trabeculectomy (group B). Short-term and long-term mean IOP
      reductions were similar in the two groups though, at 2 years, more patients in
      the standard phacotrabeculectomy group had need of medical therapy to control
      their ocular pressure (p = 0.04). Group B had less surgically induced astigmatism
      than group A (p = 0.05). There was no significant difference in ocular
      inflammation and complication rates between the 2 groups.

PMID- 9589729
TI  - Improvement of spatial contrast sensitivity threshold after surgical reduction of
      intraocular pressure in unilateral high-tension glaucoma.

PMID- 9589730
TI  - Evaluation of the choroidal and retinal blood flows by means of the pOBF system
      and the Eco-Color-Doppler in glaucomatous patients after trabeculectomy surgery.

PMID- 9589731
TI  - Surgery for normal tension glaucoma. Target intraocular pressure and visual field
      progression.

PMID- 9589732
TI  - Filtration and complications after trabeculectomy and after phaco-trabeculectomy.

PMID- 9589733
TI  - Delayed postoperative use of 5-fluorouracil in primary open angle glaucoma.

PMID- 9589734
TI  - Glaucoma and hypothyroidism.

PMID- 9589735
TI  - Comparison between computerized static perimetry and high-pass resolution
      perimetry in the follow-up of glaucomatous patients.

PMID- 9589736
TI  - The influence of diabetes mellitus on primary open angle glaucoma perimetry.
AB  - We have carried out a study into retinal sensitivity alterations in the course of
      primary open angle glaucoma to see if their appearance and evolution might be
      influenced by concomitant diabetes mellitus. The visual field examination
      (Perimeter Octopus 500 EZ, programme G1) indicated prevalent sensitivity defects
      in the superior hemifield, both in glaucoma only subjects and in those with
      diabetes as well. As to the inferior hemifield, a greater, statistically
      significant, retinal sensitivity defect was found in the inferior temporal
      quadrant of the left eye in the group of diabetics.

PMID- 9589737
TI  - Sector PERG evaluation of glaucomatous damage.

PMID- 9589738
TI  - Conjunctival vs sublingual administration of carteolol 2% eye drops. Ocular
      hypotensive effects and some systemic parameter changes.

PMID- 9589740
TI  - Prepared association of metipranolol 0.1% + pilocarpine 2% and of timolol 0.5% +
      pilocarpine 2%. Comparison of clinical efficacy and topical tolerability in the
      treatment of patients affected by POAG tonometrically uncontrolled with beta
      blocker alone (two-centre study).

PMID- 9589739
TI  - Chronic topical eye preservative-free beta-blocker therapy effect on the ocular
      surface in glaucomatous patients.

PMID- 9589741
TI  - Ocular tension and pupil diameter effects of timolol 0.50% and pilocarpine 2% or
      4% in association.

PMID- 9589742
TI  - The use of flunarizine in the management of low-tension glaucoma: a color Doppler
      study.
AB  - The authors assess the efficacy of flunarizine in improving blood flow and
      perimetric indices in low-tension glaucoma (LTG). A group of 20 patients with LTG
      well-compensated by medical treatment underwent Color Doppler Imaging (CDI) of
      the ophthalmic artery and posterior ciliary arteries with peak systolic velocity
      (PSV) and Purcelot's index (PI) evaluation. Computerized perimetry was also
      performed to assess MD, SF and CPSD. The parameters were measured before and
      after three months' therapy with flunarizine. Data before and after flunarizine
      treatment were: Ophthalmic artery- PSV 33.261 +/- 1.628 cm/sec vs 35.746 +/-
      0.800 cm/sec (p < 0.001); PI 0.697 +/- 0.017 vs 0.627 +/- 0.031 (p < 0.001);
      Posterior ciliary arteries- PSV 9.385 +/- 0.751 cm/sec vs 10.738 +/- 1.566 cm/sec
      (p < 0.005); PI 0.673 +/- 0.056 vs 0.589 +/- 0.023 (p < 0.001). The perimetric
      indices were modified as follows: MD -11.002 +/- 6.574 vs -6.604 +/- 6.426 (p <
      0.006); SF 5.05 +/- 5.717 vs 2.937 +/- 1.780 (p < 0.193); CPSD 10.198 +/- 13.392
      vs 3.445 +/- 2.709 (p < 0.093). Oral administration of flunarizine, a calcium
      channel-blocker which acts at a vascular and neuronal level, improves the blood
      flow indices for the optic nerve, improving thereby the perimetric indices in
      LTG.

PMID- 9589743
TI  - Antimetabolites in glaucoma surgery: our experiences and results.

PMID- 9589744
TI  - Intraocular pressure increase after phacoemulsification and foldable silicone
      lens implantation using Healon GV.

PMID- 9589745
TI  - Health policy for the aged. We don't study the right people.
AB  - A review of articles on aging published during one year in seven major U.S.
      journals in the fields of general medicine, public health and gerontology showed
      that only a minority of studies took into consideration the factual attributes of
      the population. Only 53% of the articles included any basic demographic
      information, usually age. Race was mentioned in 37%, but only 3% studied blacks
      or Hispanics; socioeconomic status was given in 25%, marital status in 9%, and
      education in 19%. Regardless of whether demographic factors were detailed in the
      description of the study, they were rarely used in the analysis. We conclude that
      information obtained in the course of studies of the elderly may not reflect the
      actual needs of this population group which must be recognized as heterogeneous.
      More specific and refined data are needed to set priorities and make policy
      decisions.

PMID- 9589747
TI  - Physical activity and cardiovascular health in the elderly.
AB  - People over the age of 65 constitute a growing proportion of the world population
      both in western and in developing countries. A unique feature of this group is
      the high prevalence of cardiovascular diseases, which negatively affect its
      quality of life as well as its life expectancy. Among the interventions able to
      reduce the health burden of cardiovascular diseases is physical activity. The
      benefits of physical activity have been demonstrated both in healthy and
      chronically ill elderly subjects, while the risks have been found to be modest.
      Physicians should recommend moderate-intensity physical activity to sedentary
      older subjects, who are still the majority within the elderly population.

PMID- 9589746
TI  - Therapeutic management of hematological malignancies in elderly patients.
      Biological and clinical considerations. Part IV: Multiple myeloma and
      Waldenstrom's macroglobulinemia.
AB  - Following recent data on multiple myeloma (MM) in the literature, a possible
      model of myeloma development, involving different cytokine signals, is advanced,
      and the prognostic significance of two principle staging systems is evaluated.
      Different therapeutic approaches to MM have been employed, consisting of either
      treatment with only melphalan and prednisone, or combination chemotherapy,
      especially in patients with a poor prognosis. However, for the initial therapy,
      melphalan plus prednisone in doses that compensate for individual variation in
      drug absorption still appears the best choice in the vast majority of MM
      patients. The main clinical and hematological features which distinguish
      Waldenstrom's macroglobulinemia from MM are described, as are the criteria which
      should be used in choosing the most appropriate treatment based, when necessary,
      on chemotherapy with standard alkylating agents, as well as on the new nucleoside
      analogues, and repeated courses of plasmapheresis.

PMID- 9589748
TI  - Reliability of four simple, quantitative tests of balance and mobility in healthy
      elderly females.
AB  - Four common tests of balance and mobility were administered to 45 healthy women,
      aged 55-71 years: Sharpened Romberg (also defined as tandem stance), eyes open
      and closed; One-Legged Stance Test, eyes open and closed; Functional Reach; and
      Sit-To-Stand test. Two independent observers scored the tests, which were
      performed on two successive days. Inter-rater (IRR) and test-retest reliability
      (TRR) were good. Across the six different tests, Intraclass Correlation
      Coefficients ranged from 0.95 to 0.99 for scoring consistency between rates, and
      from 0.73 to 0.93 within raters. This is in line with previous findings based on
      similar subjects and similar, though not identical, testing procedures.
      Intercorrelations between the scores were moderate: r coefficients ranged 0.40
      0.66. The results suggest that this simple test battery provides reliable scores,
      and that the different tests relate to a homogeneous construct, while not being
      redundant. It thus seems worthwhile to further investigate whether they represent
      and measure a unidimensional domain, rather than conceptually different
      dimensions, in view of achieving a unique measure of balance performance.

PMID- 9589749
TI  - Relationship between routine hematological parameters, serum IL-3, IL-6 and
      erythropoietin and mild anemia and degree of function in the elderly.
AB  - To investigate the influence of functioning on unexplained senile anemia, we
      measured commonly used hematological parameters (serum iron, transferrin, iron
      saturation and ferritin) in addition to specific erythropoietic factors, such as
      interleukin-3 (IL-3), interleukin-6 (IL-6), and erythropoietin (EPO) in 48
      elderly subjects aged 65-90 years. The subjects were divided into 3 groups: 1) 17
      patients with unexplained mild anemia; 2) 17 non-anemic patients with newly
      acquired stroke and who previously were functionally active; 3) 14 functionally
      active patients with no major disease who served as controls. Anemia was defined
      as hemoglobin (Hb) values under 12.0 g/dL. The degree of functional ability was
      defined and scored by the "functional independence measure" (FIM) test. Data are
      presented as mean values +/- SD. The results revealed a correlation between the
      functional state and levels of Hb, iron and transferrin with unchanged iron
      saturation. Patients in the mild anemia group were found to be functionally
      declined (FIM = 57 +/- 19.4) with the relatively lowest mean iron (75.1 +/- 17
      micrograms/dL) and transferrin levels (243 +/- 42.6 micrograms/dL). The stroke
      group (FIM = 62 +/- 17.7) had intermediate levels of iron (85.4 +/- 20.3
      micrograms/dL) and transferrin (245 +/- 45.2), and with the continuation of the
      declined functional state the Hb level decreased significantly (13.7 +/- 0.9 to
      12.0 +/- 1.0 g/dL, p < 0.001). The highest mean values of iron (102 +/- 27.9
      micrograms/dL) and transferrin (322 +/- 42.7 micrograms/dL) were found in the
      control group (FIM = 122.7 +/- 5.8). The ferritin levels showed an opposite
      trend. IL-3 values were undetectable in the anemic and control groups, and were
      elevated in some patients in the stroke group. The lowest IL-6 level was observed
      in the anemic group, and the highest in the control group. Serial IL-6 assays in
      the stroke group showed an upward trend. Erythropoietin levels in all groups
      showed no difference.

PMID- 9589750
TI  - Development and validation of a clinical history form for the diagnosis of
      congestive heart failure.
AB  - Our aim was to develop and validate a new diagnostic tool for congestive heart
      failure (CHF) based only on clinical examination, medical history and current
      drug use. In the developmental phase, we enrolled 520 consecutive patients with
      heart disease of different etiology; the diagnosis of CHF was made by means of
      Smith's clinical and radiological criteria, and the Boston criteria, with a
      substantial interscale agreement (kappa = 0.89). The initial version of our Form
      included 37 items on clinical examination, medical history and drug use
      information. After an item reduction process, the final version of the Clinical
      History Form (CH Form) included 15 items, each with a score 1 to 4. The CH Form
      score showed a progressive, significant increase as NYHA Class increased. With a
      cut-off of 4 points, sensitivity was 88.6% and specificity 86.8% against Smith's
      criteria for diagnosis of CHF. Substantial interrater agreement was observed for
      all the 15 items (kappa > 0.6) on a subsample of 250 patients. In the validation
      phase, we studied an independent sample of 72 patients with heart disease. The CH
      Form was significantly correlated with left ventricular ejection fraction (r =
      0.42; p < 0.0005) and peak oxygen consumption (r = 0.69; p < 0.0001). In the 64
      (89%) patients who underwent non-emergent right-heart catheterization, the CH
      Form score was significantly correlated with pulmonary capillary wedge pressure
      (r = 0.84; p < 0.0001). The CH Form may represent a useful instrument for the
      diagnosis of CHF.

PMID- 9589751
TI  - Correlation between aortic pulse wave velocity and norepinephrine, epinephrine,
      aldosterone and plasma renin activity in very elderly subjects and in patients
      with congestive heart failure.
AB  - The expression of cardiovascular disease in older patients results from the
      interaction between age-related changes and the disease process itself. It is
      still unclear whether the physiologic and pathophysiologic changes that occur
      with advanced age accelerate or compound the factors responsible for congestive
      heart failure (CHF). Whether, and to what extent, arterial compliance is altered
      in CHF in the elderly is not clear. It is also unknown whether the plasma levels
      of neurohumoral factors in the healthy elderly and in CHF patients are associated
      with changes in arterial compliance. The aim of this study was to evaluate the
      aortic pulse wave velocity (PWV) in the aorta of elderly healthy subjects and CHF
      patients, and establish the correlation between PWV and plasma levels of
      norepinephrine, epinephrine, aldosterone, and renin activity. The study group
      consisted of 63 females aged 70-100 years (mean, 82 years) with CHF, and 15 age
      matched healthy women. Aortic PWV in patients with heart failure did not differ
      significantly from figures in the age-matched healthy group (12.42 m/sec vs 11.86
      m/sec). No statistically significant correlations were found between plasma
      levels of norepinephrine, epinephrine, aldosterone and renin activity, and aortic
      compliance measured as PWV. These results suggest that age-associated arterial
      stiffening is a predominant factor in the development of reduced arterial
      compliance in elderly patients with CHF.

PMID- 9589752
TI  - Epidemiology of osteoporosis in women in southern Italy.
AB  - Studies on the distribution of bone mineral density (BMD) values in different age
      groups and in different populations are valuable for understanding the causes of
      the appreciable geographical variability in fracture incidence. We studied a
      population of southern Italy in an area where the incidence of hip fracture had
      been previously estimated. With a completion rate of 85%, we recruited a group of
      264 women between 45 and 79 years of age, representative of non-institutionalized
      and active women in the population, and measured bone density both at the lumbar
      spine (L1-L4) and at the right femoral neck using a dual X-ray absorptiometry
      (DEXA) system. We report the age group distribution of BMD in this population.
      The elderly showed higher mineralization, as compared to an international pooled
      sample. The prevalence of osteoporosis among women of 50-79 years of age was 40%;
      the rate changed according to the measurement site. Our results show that a large
      proportion of women would not have been diagnosed as having osteoporosis if we
      had relied on a single measurement site. A very low percentage of cases (as low
      as 4% in the 50-59 years age group) was diagnosed at both sites. The lack of
      concordance in BMD estimate between measurement sites is significant at younger
      ages, with an almost dichotomous distribution of cases diagnosed either at the
      lumbar or femoral site, suggesting the hypothesis that distinct patterns of bone
      involvement and bone mass lowering exist and all eventually lead to systemic
      involvement. Longitudinal follow-up of this population should help address some
      of the questions raised by these results.

PMID- 9589753
TI  - Immobilization effects on contractile properties of aging rat skeletal muscle.
AB  - The effect of four weeks of ankle immobilization on muscle mass and in situ
      contractile properties of soleus (SOL), plantaris (PLA), and extensor digitorum
      longus (EDL) of 31- and 37-month-old (mo) Fisher 344/Brown Norway rats was
      examined. Following contractile tests, muscles were harvested, weighed, and
      analyzed for fiber type and fiber cross-sectional area. Body weights (g) were
      similar in both control (CON) groups (31 mo, 578 +/- 20; 37 mo, 553 +/- 26; mean
      +/- SE) and both immobilized (IM) groups (31 mo, 496 +/- 6; 37 mo, 461 +/- 15).
      Immobilization-related differences in peak tetanic tension (g) were less in 37 mo
      than 31 mo rats (age x treatment, p < 0.05) for SOL (31 mo, CON 156 +/- 11, IM 63
      +/- 12; 37 mo, CON 70 +/- 6, IM 46 +/- 8), PLA (31 mo, CON 435 +/- 13, IM 239 +/-
      40; 37 mo, CON 155 +/- 14, IM 152 +/- 20) and EDL (31 mo, CON 227 +/- 13, IM 139
      +/- 17; 37 mo, CON 117 +/- 16, IM 108 +/- 4). Immobilization-related differences
      in muscle mass (mg) were smaller in 37 mo rats compared to 31 mo animals for SOL
      (31 mo, 206 +/- 14 vs 129 +/- 8, 37 mo, 148 +/- 5 vs 114 +/- 2, age x treatment p
      < 0.06) and PLA (31 mo, 409 +/- 14 vs 257 +/- 22, 37 mo, 234 +/- 17 vs 181 +/-
      18, age x treatment p < 0.05), but immobilization-related muscle mass differences
      were similar in both age groups for EDL (31 mo, 178 +/- 7 vs 134 +/- 9; 37 mo,
      157 +/- 10 vs 112 +/- 7). There were no immobilization-related changes in fiber
      type distribution in any of the three muscles studied in either age group. The
      results suggest that disuse-related change is diminished when superimposed on
      muscles that have already undergone marked age-related decline.

PMID- 9589754
TI  - Notation of previous falls in admission record of hospitalized elderly.
AB  - To test the hypothesis that a history of falling is underreported by physicians
      and nurses, we assessed the extent to which previous falls are noted in the
      admission medical history. A total of 168 community-dwelling and
      institutionalized elderly adults, > or = 70 years old, were evaluated in the
      emergency ward of a tertiary care community-based teaching hospital, and admitted
      to a general medical ward. Physicians' and nurses' emergency ward and admission
      notes were reviewed for the inclusion of "falls." Within 72 hours of admission,
      the information provided or omitted in the medical record was confirmed or
      refuted by face-to-face interview. Follow-up data were gleaned from computer
      based records. The sample population consisted of 113 patients, 56% female, with
      a mean age of 80.7. Seventy-six patients had fallen within the past 10 years: of
      these, 32 (42%) were Recent Fallers, and 44 (58%) were Multiple Fallers. Review
      of the medical records revealed that 56 (74%) of the 76 Fallers were not noted to
      have fallen by the medical staff. Moreover, 15 (47%) of the Recent Fallers and 28
      (64%) of the Multiple Fallers were missed. Examination of the nursing notes
      yielded similar results. In conclusion, elderly patients fall more frequently
      than recognized. Physicians and/or nurses should include a question regarding
      falls as part of the routine medical history.

PMID- 9589755
TI  - Brief history, current status, and future place of assertive community treatment.

PMID- 9589756
TI  - A research network to evaluate assertive community treatment: introduction.

PMID- 9589757
TI  - Cost-effectiveness of assertive community treatment teams.
AB  - Clients who were high service users with serious mental disorders were randomly
      assigned to assertive community treatment (ACT) or to standard case management
      (SCM) at three sites and followed for 18 months. Clients in ACT spent more days
      in the community than did those in SCM, at no additional cost. For clients who
      were hospitalized at study entry, assertive community treatment was more cost
      effective than standard case management.

PMID- 9589758
TI  - Intersite variation in the impact of intensive psychiatric community care on
      hospital use.
AB  - Differences among treatment facilities in effectiveness of intensive psychiatric
      community care (IPCC) for reducing hospital dependence are examined. Experimental
      data from nine VA hospitals showed IPCC to be most effective where former
      orientation to inpatient care was changing to improved accessibility of
      outpatient services. These hospitals appeared to have the greatest need for
      community care programs and to be most committed to shifting their system of
      service delivery.

PMID- 9589759
TI  - Assertive community treatment for patients with co-occurring severe mental
      illness and substance use disorder: a clinical trial.
AB  - Integrated mental health and substance abuse treatment within an assertive
      community treatment (ACT) approach was compared to that within a standard case
      management approach for 223 patients with dual disorders over three years. ACT
      patients showed greater improvements on some measures of substance abuse and
      quality of life, but the groups were equivalent on most measures, including
      stable community days, hospital days, psychiatric symptoms, and remission of
      substance use disorder.

PMID- 9589761
TI  - Transferring clients from intensive case management: impact on client
      functioning.
AB  - The effects of transferring clients from assertive community treatment to a less
      intensive (step-down) case management program were examined. Service use
      decreased significantly after transfer to the step-down program, and no negative
      effects of transfer on hospital use or client functioning were evident. Critical
      elements for successful step-down are suggested and discussed.

PMID- 9589760
TI  - Program fidelity in assertive community treatment: development and use of a
      measure.
AB  - Assertive community treatment (ACT) is a complex community-based service approach
      to helping people with severe mental disorders live successfully in the
      community. Effective replication of the model and research on critical elements
      require explicit criteria and measurement. A measure of program fidelity to ACT
      and the results of its application to fifty diverse programs are presented.

PMID- 9589762
TI  - Methodological issues in assertive community treatment studies.
AB  - Recent evaluations of ACT programs have produced equivocal findings, often
      leading to the invocation of methodological problems as responsible for the lack
      of positive results. This paper discusses issues of theory and methodology as
      they pertain to improving research of ACT, with particular attention paid to
      issues of sampling, process evaluation, measurement, and data analysis.

PMID- 9589763
TI  - Links between research findings and the future of assertive community treatment:
      a commentary.

PMID- 9589764
TI  - Predictors and characteristics of mental health among men at midlife: a 32-year
      longitudinal study.
AB  - In a prospective, 32-year longitudinal study of 87 young men originally selected
      for general health, it was found that good physical and mental health were
      maintained by most. Successful predictors of midlife mental health included
      satisfactory peer social adjustment, little or no angry behavior, and a mentor
      relationship in young adulthood. Overall findings suggest that mental health is
      closely associated with developing social relationships.

PMID- 9589765
TI  - Suicidal behavior in adolescents: stress and protection in different family
      contexts.
AB  - Recent suicidal behavior was reported on a questionnaire by 14% of 272 high
      school students. Two-thirds of the suicidal teenagers neither received help nor
      disclosed their self-harm to anyone. Depression and stress--especially family
      suicidality, feelings of violation, and sexuality--increased the risk, as did
      parental separation, divorce, and most dramatically, remarriage. Family
      cohesiveness helped alleviate the risk in the nonintact families.

PMID- 9589766
TI  - Treatment involvement and outcomes for four subtypes of homeless veterans.
AB  - A longitudinal study examined treatment services and outcomes in a nationwide
      sample of 565 homeless veterans who were classified as alcoholic, psychiatrically
      impaired, multiproblem, or best-functioning. All four groups experienced some
      improvement in their primary problem area, in employment status, and in
      residential quality at eight-month follow-up, but there were significant
      differences in degree of improvement across groups. Implications for the design
      of homeless programs and policies are discussed.

PMID- 9589767
TI  - Bias in child maltreatment reporting: revisiting the myth of classlessness.
AB  - Data on the degree of class bias in child protective services databases are
      reviewed, along with recent empirical findings on the class distribution of child
      maltreatment. The evidence suggests high levels of child abuse and neglect among
      the poor and, despite debate on the question, there is no body of empirical data
      suggesting that these findings are a product of bias predisposing toward
      overestimates of child maltreatment among the poor. Implications for research,
      practice, and policy are offered.

PMID- 9589768
TI  - Toward a new definition of hallucination.
AB  - Two major flaws in the DSM-IV definition of hallucination are addressed: 1) it
      fails to distinguish pathological from nonpathological experiences; and 2) it
      fails to consider cultural beliefs in determining whether an experience is
      hallucinatory. These omissions are discussed within the context of an evolving
      concept of the term hallucination and an expanding vocabulary used to describe
      unshared sensory experiences. A revised definition is proposed.

PMID- 9589769
TI  - The construction of the crack babies phenomenon as a social problem.
AB  - Early negative findings on cocaine-exposed newborns engendered widespread media
      and public perceptions of a causal link between poor mothers' substance use and
      serious problems in their offspring. Despite later research questioning the
      prevalence of the problems and implicating other environmental and economic
      factors, these mothers were stigmatized and criminalized, and their children
      precipitously removed from their care. This paper reviews the process by which
      this came about and urges a more balanced and complex view of the problem.

PMID- 9589770
TI  - Children's beliefs about people labeled mentally ill.
AB  - A group of 104 third-grade students told stories in response to pictures of
      adults labeled mentally ill, physically disabled, or unlabeled, and answered
      questions regarding expected behavior of these adults. Results indicate that,
      children of this age hold more overall negative attitudes about adults labeled
      mentally ill than about those designated as physically disabled or nondisabled.

PMID- 9589771
TI  - The role of sibling support in high-conflict families.
AB  - Effects of sibling support on the relationship between family conflict and
      individual psychological adjustment was explored in a sample of university
      students. Those from high-conflict homes with high sibling support reported more
      positive adjustment than did only-children and individuals with low sibling
      support. Sibling support was not associated with greater adjustment in low
      conflict homes, thus reinforcing its potential benefits as a buffer to stress.

PMID- 9589772
TI  - Nutrient induced thermogenesis.
AB  - Although first described more than two centuries ago, the increase in energy
      expenditure associated with feeding (nutrient induced thermogenesis (NIT) is
      still incompletely understood. Although the magnitude of the response and the
      effect of varying the composition of the diet, route and rate of feeding is still
      the subject of controversy, the importance of taking into account NIT when
      designing an optimal feeding regimen is well recognised. What is currently
      unclear is the effect that injury or sepsis have on NIT. This is of clinical
      significance because it is precisely this group of patients in whom adequate
      nutritional support is most difficult to achieve yet most important. Despite
      significant differences in the metabolic response to feeding, NIT appears to be
      similar in septic patients and healthy subjects. Excessive use of intravenous
      glucose in such patients however may lead to marked increases in energy
      expenditure and stimulation of the sympathetic nervous system and should be
      avoided.

PMID- 9589773
TI  - Regional contribution to hypermetabolism following trauma.
AB  - Severe injuries are associated with a systemic inflammatory response. This
      inflammatory response is qualitatively similar in trauma and sepsis, and its
      magnitude depends on the severity of the inflammatory stimulus. The
      hypermetabolism induced by injury does not affect the whole body uniformly. The
      splanchnic region appears to be the main source of the hypermetabolic response in
      various types of trauma and inflammation. The increased splanchnic metabolic
      activity is not fully matched by concomitant increases in blood flow. This
      mismatch of metabolic demand and blood flow increase the risk of inadequate
      tissue perfusion in the splanchnic region. In the acute phase of injury this risk
      is magnified by the common presence of inadequate blood volume during the
      resuscitation from trauma. Hypovolaemia-induced splanchnic vasoconstriction
      persists even after correction of the hypovolaemia, which further increases the
      risk of inadequate perfusion of the splanchnic bed. Splanchnic hypermetabolism
      explains most of the hypermetabolic response to injury.

PMID- 9589774
TI  - Techniques for assessing protein and glucose kinetics.
AB  - Isotopic labelling techniques can lead to a better understanding of the changes
      in substrate flow resulting from trauma and other pathological conditions. This
      article describes the basic approaches used to measure rates of substrate flow,
      especially those using stable isotopes, and their application to the study of
      glucose and protein kinetics. Methods for measuring glucose turnover and
      gluconeogenesis in the whole body by constant infusion of different labelled
      forms of glucose are explained. The advantages of measuring regional rates of
      glucose metabolism, using arteriovenous balance of tracer and tracee, are
      illustrated with results demonstrating the role of gluconeogenesis by the kidney.
      Similar approaches are used to measure protein turnover rates in the whole body
      and in specific regions, with labelled amino acids such as [1-13C]leucine. In
      addition, rates of protein synthesis in individual tissues can be assessed by
      measuring the incorporation of tracer into protein of a biopsy sample. The
      relative merits of two methods of giving the tracer, by constant infusion or by
      flooding injection are explained, with examples of studies of muscle protein
      synthesis in surgical patients.

PMID- 9589775
TI  - Substrate utilization/insulin resistance in sepsis/trauma.
AB  - Endogenous substrate metabolism is markedly altered in critically ill patients.
      Glucose production is elevated not only in the post-absorptive state, but the
      normal suppressive effect of exogenous glucose and glucose production is greatly
      diminished. In the post-absorptive state, glucose clearance is generally
      elevated, potentially causing hypoglycaemia in extreme cases. Somewhat
      paradoxically, the ability of insulin to stimulate glucose uptake is diminished,
      so that hyperglycaemia is often evident during nutritional intake. Lipolysis, the
      breakdown of peripheral fat, is accelerated, meaning that free fatty acids are
      released into plasma at a rate far exceeding their oxidation. Some of the excess
      fatty acids are re-esterified in the liver, leading to accelerated hepatic
      triglyceride formation. A large increase in hepatic triglyceride stores can ensue
      if the rate of excretion of triglycerides in very low density lipoproteins is not
      accelerated commensurately with the increased triglyceride production. Indirect
      calorimetry measurements support the notion that the large increase in
      availability of fatty acids may lead to a greater reliance on fatty acids as
      energy substrates. Nonetheless, carbohydrates should be the predominant source of
      non-protein calories, because the accompanying insulin response effectively
      enhances protein synthesis. There is already ample fat available via endogenous
      lipolysis, and more fat given exogenously provides little further benefit.

PMID- 9589776
TI  - In vivo inter-organ protein metabolism of the splanchnic region and muscle during
      trauma, cancer and enteral nutrition.
AB  - The study of protein kinetics has entered a new era by the recognition that whole
      body protein turnover only poorly reflects the true events occurring in several
      organs and with regard to the multitude of proteins present in the body. It is
      also increasingly recognized that the simultaneous synthesis and degradation of
      proteins is important in regulation and adaptation during several metabolic
      conditions like starvation, feeding, after trauma, and during exercise.
      Especially important is the recognition that the kinetics of individual proteins
      may change in opposite directions, thereby leading to fluxes of alpha-amino
      nitrogen that serve to adapt to and survive a changing environment. At present,
      much emphasis is put upon molecular biological regulation. However, it is
      important that the metabolic processes that occur in the intact organism are
      still poorly defined. New technology allows the exploration of these processes,
      which should therefore prompt the initiation of further research in this area.

PMID- 9589777
TI  - The role of IGFs in catabolism.
AB  - The hypercatabolic response to trauma, extensive surgery and sepsis is
      characterized by an increased metabolic rate, severe muscle wasting and a
      negative nitrogen balance. This process of 'autocannibalism' may be in part a
      consequence of a disordered growth hormone (GH)/insulin-like growth factor (IGF)
      axis. In this chapter the normal physiology of the GH/IGF axis is first briefly
      reviewed. This is followed by a discussion of the changes that accompany fasting
      and catabolic illness, the effects of IGF-1 administration in health and disease
      and a comparison of the effects of IGF-1, GH and insulin on catabolism. Although
      initial investigations of IGF-1 administration in animals and human volunteers
      have often been encouraging, studies in catabolic patients have so far proved
      disappointing. Combined treatment with GH, IGF-1 (and insulin) or with IGF-1 and
      its major binding protein, may prove more effective, especially when used in
      conjunction with nutritional supplements such as glutamine.

PMID- 9589779
TI  - Immunonutrition.
AB  - The immune system is designed to protect the individual from foreign substances
      or organisms. It is expressed as cellular and humoral immunity. The former is
      dependent upon T lymphocytes and the latter on B lymphocytes, which become plasma
      cells and secrete antibodies. The immune system can be influenced by protein
      energy malnutrition (PEM) and by catabolic illnesses such as sepsis and trauma,
      which in turn cause PEM. Specific trace element and vitamin deficiencies can also
      alter the immune state. However, overnutrition and obesity can also influence
      immune mechanisms. Obesity can promote the development of diabetes, which can
      alter the immune state. Finally, immunity becomes less effective with ageing and
      this process is enhanced by associated malnutrition.

PMID- 9589778
TI  - The role of growth hormone in substrate utilization.
AB  - Substrate fluxes in response to growth hormone administration depend on both the
      calorie as well as acid-base balance. Growth hormone's acidogenic action as a
      consequence of promoting fatty acid utilization yields protons required for
      driving hepatic glutamate efflux; effective uncoupling of nitrogenous precursors
      from ureagenesis and recycling as glutamate bound for the periphery appears
      dependent upon this mechanism. Subsequent peripheral retrieval of the salvaged
      glutamate requires insulin-like growth factor-1 (IGF-1) activated uptake and acid
      base homoeostasis. In addition to this nitrogen sparing acidogenic effect, growth
      hormone is also basogenic in combination with IGF-1 and acting on the kidney as a
      target organ. Therefore acid-base and nitrogen homoeostasis are normally attuned
      to one another through the co-ordinated action of growth hormone/IGF-1 on
      substrate fluxes. However during starvation ketoacid production as the
      consequence of incomplete fatty acid oxidation and ketone excretion swamps the
      basogenic limb and full-blown metabolic acidosis prevails; under this condition
      growth hormone's effectiveness in sparing nitrogen for anabolic processes is
      curtailed as glutamate (emanating from the liver) and glutamine (derived from
      muscle proteolysis) are directed to the kidneys, supporting ammoniogenesis:
      nitrogen balance is now sacrificed for acid-base homoeostasis. Underlying this
      state is an intracellular acidosis that may contribute to insulin resistance and
      developing hyperglycaemia in response to growth hormone. In acute injury, an
      additional acid load contributed from muscle proteolysis and cytokines reinforces
      an intracellular acidosis that further blunts growth hormone responsiveness and
      suppresses coupled IGF-1 production. From this perspective growth hormone's
      acidogenic and basogenic actions should balance for an effective anabolic
      response during hypermetabolic catabolic illnesses.

PMID- 9589780
TI  - Direct microcalorimetry as a technique in cell cultures.
AB  - In vitro studies of energy metabolism in isolated cells contribute to improved
      knowledge of human energy metabolism under normal and pathological conditions. In
      every cellular system energy is taken up, metabolized and finally transformed
      into heat, which is dissipated into the environment. Thus, energy turnover of
      isolated cells can be assessed by microcalorimetric determination of their heat
      production. Microcalorimeters of the thermopile heat conduction type facilitate
      direct physical determination of thermogenesis with a sensitivity of 0.2 microW;
      10(4)-10(5) cells being sufficient for one measurement. Peltier elements are
      sandwiched between the sample and a precisely thermostated heat sink, creating a
      detectable voltage proportional to the heat production. For adequate
      interpretation of the results, simultaneous biochemical investigations of
      relevant metabolic pathways are required. Up to now, numerous studies with blood
      cells, skeletal and heart muscle cells, hepatocytes, endothelial cells,
      fibroblasts and adipocytes have been performed in relation to various diseases
      and under the influence of certain hormones and pharmacological agents.

PMID- 9589781
TI  - Assessing the efficacy of nutritional support.
AB  - This review outlines the conventional methods of assessing nutritional status and
      their limitations in the presence of acute trauma and sepsis. It also discusses
      the problems of attempting to improve or at least maintain nutritional status in
      the presence of an inflammatory stimulus. Most of the conventional markers of
      nutritional status are altered in trauma and sepsis with decreases in plasma
      protein concentrations and muscle strength, an apparent depression of immune
      function and an increase in extracellular fluid volume. It also appears to be
      impossible to improve nutritional status in the presence of a severe inflammatory
      stimulus, and the most one can hope for is to attenuate the rate of decline. The
      evidence for these observations is discussed.

PMID- 9589799
TI  - Teaching and training laboratory professionals for the 21st century.
AB  - Educational activities are a background to research and to a dynamic, developing
      discipline. The principles now being applied in undergraduate curricula are
      applicable to teaching and training in laboratory medicine. A fresh look at the
      education and training and an implementation of new educational techniques is
      necessary to prepare a cadre of individuals who will be developing laboratory
      medicine in the 21st century.

PMID- 9589800
TI  - Comparison of two reverse transcription-polymerase chain reaction methods for
      detection of AML1/ETO rearrangement in the M2 subtype of acute myeloid leukaemia.
AB  - Two reverse transcription-polymerase chain reaction methods to detect the
      AML1/ETO rearrangement in the M2 subtype of acute myeloid leukaemia those of
      Downing et al. (Blood 1993; 81: 2860-5) and Satake et al. (Br J Haematol 1995;
      91: 892-8) were evaluated. Bone marrow samples, one at diagnosis and two in
      complete remission from a patient with M2 subtype of acute myeloid leukaemia,
      with t(8;21), were analysed using both methods. The Kasumi-1 cell line was used
      as a positive control and a patient with M3 subtype of acute myeloid leukaemia as
      a negative control. To confirm the feasibility of Satake's method a group of 35
      patients with subtypes of acute myeloid leukaemia at diagnosis were studied. The
      method of Downing requires Southern blotting and hybridization with a specific
      probe because it often generates non-specific amplification products. By
      contrast, the method of Satake yields only a single amplification product, using
      one single round of PCR in samples at diagnosis, or two rounds in complete
      remission samples. The sensitivity of this method allows the detection of a
      single Kasumi-1 cell in 10(6) normal cells. The AML1/ETO rearrangement was
      observed in 5 of the 35 cases of acute myeloid leukaemia at diagnosis (14.3%) and
      in 3 of the 14 cases of M2 subtype of acute myeloid leukaemia (21.4%). The two
      remaining positive cases corresponded to the acute myeloid leukaemia subtypes M4
      and M6. The results indicate that the method of Satake better meets the
      requirements of the clinical laboratory due to its greater simplicity,
      specificity, sensitivity and feasibility, thus making it more appropriate for use
      in diagnosing and monitoring minimal residual disease.

PMID- 9589801
TI  - The effect of ascorbic acid ingestion on the biochemical and physicochemical risk
      factors associated with calcium oxalate kidney stone formation.
AB  - The present study was undertaken to determine the effect of ingestion of large
      doses of vitamin C on urinary oxalate excretion and on a number of other
      biochemical and physicochemical risk factors associated with calcium oxalate
      urolithiasis. A further objective was to determine urinary ascorbate excretion
      and to relate it qualitatively to ingested levels of the vitamin and oxalate
      excretion. Ten healthy males participated in a protocol in which 4 g ascorbic
      acid was ingested for 5 days. Urines (24 h) were collected prior to, during and
      after the protocol. The urine collection procedure was designed to allow for the
      analysis of oxalate in the presence and absence of an EDTA preservative and for
      the analysis of ascorbic acid by manual titration using 2,6
      dichlorophenolindophenol. Physicochemical risk factors such as the calcium
      oxalate relative supersaturation and Tiselius risk index were calculated from
      urine composition. The results showed that erroneously high analytical oxalate
      levels occur in the asence of preservative. In the preserved samples there was no
      significant increase in oxalate excretion at any stage of the protocol. Ascorbate
      excretion increased when vitamin C ingestion commenced but levelled out after 24
      hours suggesting that saturation of the metabolic pool is reached within 24 hours
      after which ingested ascorbic acid is excreted unmetabolized in the urine. While
      transient statistically significant changes occurred in some of the biochemical
      risk factors, they were not regarded as being clinically significant. There were
      no changes in either the calcium oxalate relative supersaturation or Tiselius
      risk index. It is concluded that ingestion of large doses of ascorbic acid does
      not affect the principal risk factors associated with calcium oxalate kidney
      stone formation.

PMID- 9589802
TI  - Oxidative stress and antioxidant defenses in renal patients receiving regular
      haemodialysis.
AB  - Patients with chronic renal failure, and particularly those receiving regular
      haemodialysis, have a high incidence of premature cardiovascular disease.
      Oxidative stress, which causes lipid peroxidation, may contribute to increase the
      risk of atherosclerosis. The results of the present study indicate that lipid
      peroxidation products (malonaldehyde and 4-hydroxyalkenals) are significantly
      increased in plasma of renal patients before dialysis and, although reduced,
      remained above the normal range after this treatment. Moreover, production of
      free radicals and reactive oxygen metabolites was increased in chronic renal
      failure patients, especially after dialysis. On the other hand, the antioxidant
      defenses of those patients were higher than those of normal subjects, as judged
      from the plasma levels of specific antioxidant molecules and from the plasma
      antioxidant capacity. We also found that triglycerides were significantly higher
      in renal patients, both before and after dialysis, than in the control group.
      These results suggest that patients on chronic haemodialysis are particularly
      prone to oxidative stress and that dialysis itself may worsen this condition.
      Rather than to a weakening of antioxidant defenses, the susceptibility of chronic
      renal failure patients to oxidative stress might be ascribed to an increased free
      radical and reactive oxygen metabolite production and to increased levels of
      oxidizable substrates, notably triglycerides with their unsaturated fatty acids.

PMID- 9589803
TI  - Development of an HPLC assay to study the effect of endogenous and exogenous
      substances on heat-induced aggregation of human serum albumin.
AB  - The mechanism of action of non-steroidal anti-inflammatory drugs which are used
      in high doses in chronic inflammatory conditions is not clearly understood. Their
      known protein-stabilizing properties could play a significant role. The
      inhibition of cyclooxygenase may not be essential for their anti-rheumatic
      activity, since compounds with strong anti-denaturant properties and devoid of
      anti-inflammatory activity were shown to be effective in an experimental model of
      rheumatoid arthritis. Hence, to develop new anti-rheumatic drugs it is essential
      that a simple in vitro method to evaluate the anti-denaturant activity of
      endogenous and exogenous compounds is available. We developed a new assay, using
      gel permeation high performance liquid chromatography, to study the effect of
      endogenous and exogenous compounds on heat-induced aggregation of human serum
      albumin in conditions in which protein precipitation does not occur. Non
      steroidal anti-inflammatory drugs like diclofenac, ibuprofen and naproxen
      inhibited the aggregation of albumin at low concentrations (EC50 10(-4)-10(-5)
      mol/l) comparable to those active in a classical turbidimetric method, whereas
      the effect of weak stabilizers, like sodium cloride and formic, fumaric, maleic,
      malonic, and succinic acid (EC50 10(-1)-10(-2) mol/l in the Mizushima test) was
      not detectable. Furthermore, the HPLC assay allowed the examination of a number
      of coloured substances, including bilirubin, which appeared to be a strong
      stabilizer of its physiological carrier, albumin. These data could be clinically
      relevant, since the drugs examined are used at very high doses in rheumatoid
      arthritis and related conditions, with plasma levels that could cause significant
      stabilization of serum albumin and perhaps other proteins.

PMID- 9589804
TI  - Assessment of serum total and bone alkaline phosphatase measurement in clinical
      practice.
AB  - The aim of the study was to measure serum levels of the bone-specific isoenzyme
      of alkaline phosphatase in normal subjects and patients with metabolic bone
      disease by using an immunoadsorption assay. We studied 140 healthy adults, 122
      patients affected by metabolic bone disease and 15 patients with cholestatic
      liver disease. Mean values of the bone-specific isoenzyme of alkaline phosphatase
      in healthy men were significantly higher than those found in premenopausal women
      (17.8 +/- 4.2 U/l vs 15.6 +/- 4.6 U/l, p < 0.02); postmenopausal women had
      significantly higher levels of bone-specific isoenzyme of alkaline phosphatase
      (22.6 +/- 6.4 U/l) than premenopausal women (p < 0.0001). After the menopause
      total alkaline phosphatase increased by 46%, while the increase in bone-specific
      isoenzyme of alkaline phosphatase was 39%. No significant correlations were found
      between bone-specific isoenzyme of alkaline phosphatase and either age or years
      since menopause, in postmenopausal subjects. In patients with bone-specific
      isoenzyme of alkaline phosphatase above the upper limit of normal, the assay had
      a sensitivity of 100% only in patients with Paget's disease of bone. In patients
      with cholestatic liver disease we found no correlation between bone-specific
      isoenzyme of alkaline phosphatase and either total alkaline phosphatase and gamma
      glutamyl transpeptidase, while a positive correlation was found between total
      alkaline phosphatase and gamma-glutamyl transpeptidase. Our results confirm the
      role of bone-specific isoenzyme of alkaline phosphatase assay in clinical
      research; however, its usefulness in clinical practice is unclear once liver
      involvement has been excluded.

PMID- 9589806
TI  - The increase of plasma homocysteine concentrations with age is partly due to the
      deterioration of renal function as determined by plasma cystatin C.
AB  - One of the main determinants of plasma homocysteine in healthy subjects is serum
      creatinine. In the present study, we therefore investigated the relation between
      plasma homocysteine concentration, serum creatinine and a new marker for
      glomerular filtration rate, plasma cystatin C concentration. Cystatin C reflects
      the glomerular filtration better than serum creatinine and is not related to the
      muscle mass and formation of creatinine. The study group consisted of 255 healthy
      subjects from a well-defined area in the southern part of Sweden. The
      concentration of plasma homocysteine was increased in men compared to women. This
      difference disappeared when men and women were stratified by serum creatinine
      values. Statistically significant correlations were noted between plasma
      homocysteine and age, plasma cystatin C and serum creatinine. It is shown that
      plasma homocysteine is not only correlated to serum creatinine as a result of
      renal function but also as a result of the relationship between homocysteine
      production and creatine-creatinine synthesis. Using linear regression we were
      able to show that plasma cystatin C had a higher explanatory value than age.
      Serum creatinine showed a lower explanatory power than age. The findings in the
      present study might suggest that the increase of plasma homocysteine
      concentration with age could be partly due to the deterioration of renal
      function.

PMID- 9589805
TI  - The predictive value of several markers in the progression to acquired
      immunodeficiency syndrome.
AB  - Serum beta 2-microglobulin, neopterin, immunoglobulins A, G and M, adenosine
      deaminase and CD4+ lymphocyte count were evaluated as predictors of progression
      of HIV-1 infection to AIDS. A population of HIV-1 seropositive, initially
      asymptomatic men (n = 213) and women (n = 101) was followed up quarterly. We
      estimated the AIDS-free time using the actuarial method (median survival time
      47.2 months). Cox proportional hazard analysis revealed that all markers studied
      were significant (p < 0.05) in relation to progression to AIDS. The best markers
      for predicting progression to AIDS were, in descending order, CD4+ lymphocyte
      count, beta 2-microglobulin, IgA, neopterin, IgG, IgM and adenosine deaminase. On
      stratifying population into four groups (divided at percentiles 25, 50 and 75-
      from group 1, with values nearest to reference ranges, to group 4, with most
      abnormal values) we observed statistically significant differences (p < 0.05) for
      all markers except for adenosine deaminase. The relative risk from the Cox
      proportional hazards model were used to quantify the effects of the best markers
      and compared to the risk obtained in group 1. CD4+ lymphocyte count was the best
      predictor of progression to AIDS. When considering beta 2-microglobulin and CD4+
      together, the relative risk in the group with lowest CD4+ cell count (group 4)
      ranged from 25.6% (with lower beta 2-microglobulin values) to 41.1% (with higher
      beta 2-microglobulin values). Similar results were obtained when considering
      neopterin and CD4+ together. The addition of beta 2-microglobulin or neopterin
      values to CD4+ lymphocyte count improved the predictive value of CD4+ lymphocyte
      count.

PMID- 9589807
TI  - Serum CA 242: the search for a valid marker of pancreatic cancer.
AB  - Many efforts have been made to find valuable serum tumour markers which help the
      diagnosis of pancreatic cancer. In the present study we investigated the
      diagnostic value of CA 242 in comparison with two other routinely used tumour
      markers (CA 19-9 and CA 50). Two-hundred and seventy six subjects were enrolled
      in this study: 46 patients with pancreatic cancer preoperatively, 53 with chronic
      pancreatitis, 28 with acute pancreatitis, 49 with other malignancies, 50 with
      miscellaneous non-neoplastic digestive diseases, and 50 healthy subjects. CA 242
      was determined in serum by means of a two-step fluoroimmunometric assay.
      Sensitivities of CA 242, CA 19-9 and CA 50 for pancreatic cancer when all
      patients were considered were 41.3%, 54.3% and 47.8%, respectively (95%
      specificity level). No significant improvement was achieved by combination of CA
      242 with CA 19-9 and/or CA 50. Cholestasis affected serum levels of CA 242 in
      patients without pancreatic cancer, but not in those with this tumour. The
      metastatic stage of pancreatic cancer appeared to influence the levels of CA 242.
      In conclusion, CA 242 serum assay does not seem to improve diagnostic accuracy
      for pancreatic cancer compared to CA 19-9 and CA 50.

PMID- 9589808
TI  - Approved recommendation on IFCC methods for the measurement of catalytic
      concentration of enzymes. Part 9. IFCC method for alpha-amylase (1,4-alpha-D
      glucan 4-glucanohydrolase, EC 3.2.1.1). International Federation of Clinical
      Chemistry and Laboratory Medicine (IFCC). Committee on Enzymes.

PMID- 9589809
TI  - Quality of life and epilepsy: the Liverpool experience.
AB  - The use of quality of life (QOL) measures in epilepsy research is relatively
      recent compared with that in other chronic conditions such as coronary heart
      disease and diabetes. However, in recent years much research has been undertaken
      to develop and validate QOL measures for use in various groups of people with
      epilepsy, including children, the elderly, and newly diagnosed patients. QOL
      measures are now available for use in both clinical trials and primary care. The
      Liverpool Group is one of the leading research teams in this field and is
      probably best known for developing the Liverpool Seizure Severity Scale. However,
      the group has also developed a number of other QOL measures, with an emphasis on
      keeping the measures appropriate, practical, and responsive, and always
      considering the burden to patients. This review describes some of the measures
      the Liverpool Group has developed, outlines their application in clinical trials
      of a number of aspects of antiepileptic drugs, and details the importance of some
      of the findings. The diversity of the group's approach and of its involvement in
      assessing the QOL of people with epilepsy are emphasized.

PMID- 9589810
TI  - Quality of life of people with epilepsy in the United States.
AB  - Health care provision in the United States is driven by the fact that most health
      insurance is commercial and private. This leads to the tendency to view patients
      as units that will produce a future cash yield. The quality of life (QOL)
      movement in the United States is in some ways a response to this view and has a
      role in convincing insurers that new treatments and techniques are worth
      increased expenditure. In the case of epilepsy, QOL research has become essential
      in improving the quality of care offered to people with epilepsy. In this review,
      some of the outcomes of using the Quality of Life in Epilepsy questionnaire are
      reviewed, the preliminary data from a community-based study of people with
      epilepsy are described, and recent studies comparing QOL in epilepsy and other
      neurologic and nonneurologic diseases are discussed. This review illustrates the
      complexity of QOL issues and the need for the widespread use of QOL measures in
      people with epilepsy.

PMID- 9589811
TI  - Epilepsy: comprehensive care, quality of life, and factors preventing people with
      epilepsy from being employed.
AB  - This article reviews several studies of patients with intractable epilepsy
      carried out at the National Epilepsy Center, Shizuoka, Japan. These studies have
      evaluated the factors that affect the employment status of people with epilepsy
      and the effect of resective surgery for epilepsy on quality of life. It has been
      shown that although seizure status is a major factor in determining whether a
      person with intractable epilepsy finds employment, other factors also play a
      role. These other factors include intellectual impairment, psychological and
      psychiatric disorders, and physical disabilities. Thus even patients who are
      rendered seizure free may not be able to find employment. This is perhaps
      reflected in the finding that some patients who were rendered seizure free by
      resective surgery and their families were dissatisfied with the postoperative
      outcome. A number of special factors affecting the quality of life and employment
      opportunities available to people with epilepsy in Japan are also discussed.

PMID- 9589812
TI  - Pregnancy and quality of life in women with epilepsy.
AB  - Women with epilepsy have many legitimate concerns regarding the effects of their
      condition and the use of antiepileptic drugs (AEDs) on their unborn children.
      These concerns fall into four areas: increased seizure frequency, risk of birth
      defects, risks associated with breast-feeding, and psychomotor retardation
      associated with AED use. Studies have shown that many of these risks can be
      minimized with appropriate management and counseling. This review describes some
      of the data regarding these risks and how best to alter AED therapy to minimize
      them. It also reviews data showing that psychomotor retardation is generally
      transitory.

PMID- 9589813
TI  - Quality of life research in adults with epilepsy in Japan.
AB  - Quality of life (QOL) research in epilepsy is a relatively recent development,
      but the field has expanded rapidly over the past 10 to 15 years. This expansion
      has seen the development of many tools with which to measure QOL in specific
      psychosocial domains and treatment settings. However, to date the initial
      development of these tools has been in English. Tools are also necessary to
      assess the QOL of people with epilepsy in non-English-speaking countries. These
      tools can be produced in two ways: by developing original tools in the language
      spoken in the country of use, or by translating and validating tools originally
      published in English. The latter approach has the advantages of being more rapid
      and allowing cross-cultural comparisons. We have completed or are in the process
      of translating into Japanese and validating three QOL assessment tools: the
      Washington Psychosocial Seizure Inventory, the Side Effects and Life Satisfaction
      inventory, and the Quality of Life in Epilepsy questionnaire. In this article,
      the results of this process are reported and cross-cultural comparisons using
      some of these tools are made. In this way, some of the problems associated with
      translating and validating QOL assessment tools are illustrated, and differences
      and similarities in the psychosocial impact of epilepsy in different countries
      are highlighted.

PMID- 9589814
TI  - Insulin resistance: current concepts.
AB  - Insulin sensitivity varies greatly within the general population; factors
      contributing to this variability include genetic pre-disposition, obesity,
      unfavorable body fat distribution, and lack of physical activity. Impaired
      insulin sensitivity may lead to impaired glucose tolerance and, even in
      individuals with modest insulin deficiency, to the development of type 2 diabetes
      mellitus. Of equal concern in patients with impaired insulin sensitivity is the
      development of the insulin resistance syndrome, in which hypertension,
      dyslipidemia, and impaired glucose tolerance form a cluster of risk factors for
      cardiovascular disease. Treatment of insulin resistance includes metformin and
      the thiazolidinedione troglitazone. Both drugs have been shown to be effective in
      the treatment of insulin resistance, one of the central abnormalities in type 2
      diabetes mellitus. The purpose of this study was to review the current
      understanding of insulin resistance and its implications for the treatment of
      type 2 diabetes mellitus. To do this, a MEDLINE search of the clinical literature
      was conducted and the content analyzed.

PMID- 9589815
TI  - Is there a pharmacokinetic interaction between foscarnet and zalcitabine during
      concomitant administration?
AB  - Foscarnet, an antiviral agent used in the treatment of cytomegalovirus infection,
      and zalcitabine, an antiretroviral nucleoside analogue used in the treatment of
      human immunodeficiency virus infection, are commonly used concomitantly.
      Foscarnet and zalcitabine may interact pharmacokinetically, as both compounds are
      partially eliminated by renal tubular secretion. Owing to dose-related toxicities
      associated with these two drugs, it is essential that we have data regarding
      their pharmacokinetic disposition during concomitant therapy. Twelve patients
      randomly received either foscarnet (four doses) or zalcitabine (five doses)
      (Phase 1), followed by concomitant foscarnet (four doses) and zalcitabine (six
      doses) (Phase 2), followed by dosing with the drug not received in Phase 1 (Phase
      3). Following the last dose in each phase of the study, serial plasma samples
      were collected over 8 hours for zalcitabine and over 12 hours for foscarnet to
      determine the pharmacokinetics of each drug using noncompartmental analysis.
      Foscarnet plasma and urine levels were determined using high-performance liquid
      chromatography, and zalcitabine levels were determined using radioimmunoassay. No
      clinically significant alterations in the pharmacokinetics of foscarnet or
      zalcitabine occurred in this study. Thus despite the potential for foscarnet and
      zalcitabine to compete for renal tubular secretion, no apparent pharmacokinetic
      interaction exists between these two drugs at the clinically relevant doses
      studied.

PMID- 9589816
TI  - Cefdinir versus cephalexin for the treatment of skin and skin-structure
      infections. The Cefdinir Adult Skin Infection Study Group.
AB  - Because of increasing resistance to older antimicrobial agents, newer drugs need
      to be evaluated for the treatment of skin and skin-structure infections (SSSIs).
      This double-masked, randomized, comparative, multicenter study enrolled patients
      aged 13 years or older with SSSIs to receive either cefdinir 300 mg BID or
      cephalexin 500 mg QID for 10 days. Nine hundred fifty-two patients (474 in the
      cefdinir group and 478 in the cephalexin group) took part, primarily white males
      between 18 and 65 years of age. There were two follow-up visits, with efficacy
      determined at the test-of-cure visit, 7 to 16 days posttherapy. Many patients
      were not microbiologically assessable, primarily because of negative cultures at
      study admission. Patients who required surgical intervention (e.g., incision and
      drainage) at the site of infection more than 24 hours after the initiation of
      drug therapy were defined as treatment failures. Significantly more isolated
      pathogens were resistant to cephalexin than to cefdinir. In the 178 efficacy
      assessable cefdinir-treated patients, the rate of pathogen eradication was 93%
      (200/215), and the rate of successful clinical response was 88% (157/178),
      compared with 89% (221/247) and 87% (177/204), respectively, in the 204 efficacy
      assessable cephalexin-treated patients. Using confidence-interval analysis, the
      microbiologic and clinical response rates of the cefdinir-treated patients were
      statistically equivalent to those of the cephalexin-treated patients. At the
      follow-up visits, patients were questioned about any adverse events occurring
      since their previous visit. Any untoward symptom occurring during or within 2
      days after completion of drug treatment was considered an adverse reaction if the
      investigator judged it to be definitely, probably, or possibly related to the
      study drug. One hundred twenty-three (26%) cefdinir-treated patients and 77 (16%)
      cephalexin-treated patients experienced at least one adverse reaction, a
      statistically significant difference. Study drug was discontinued for adverse
      reactions in 20 (4%) cefdinir-treated patients and 13 (3%) cephalexin-treated
      patients; in the two groups, 10 and 7 patients, respectively, were discontinued
      for diarrhea. Cefdinir taken BID was as effective as cephalexin taken QID in the
      treatment of mild-to-moderate SSSIs and was well tolerated by most patients. The
      increased antibacterial activity of cefdinir must be balanced against the higher
      rate of diarrhea seen in patients treated with this drug.

PMID- 9589817
TI  - The PROTECT Study: final results of a large multicenter postmarketing study in
      patients with type 2 diabetes. Precose Resolution of Optimal Titration to Enhance
      Current Therapies.
AB  - The Precose Resolution of Optimal Titration to Enhance Current Therapies
      (PROTECT) trial was a nationwide postmarketing study designed to assess the
      effectiveness, tolerability, and safety of acarbose in patients with type 2
      diabetes mellitus. This prospective, multicenter, open-label, 28-week trial
      enrolled 6142 patients who had type 2 diabetes that was inadequately controlled
      with either diet alone or diet plus a sulfonylurea. The dosage of acarbose was
      titrated from 25 mg TID to 50 mg TID (forced titration) and then titrated from 50
      mg TID to 100 mg TID based on tolerability and efficacy. Efficacy of glycemic
      control was assessed by recording changes in glycated hemoglobin A1c (Hb A1c) and
      1-hour postprandial plasma glucose (PPG) levels. Tolerability and safety were
      determined on the basis of patients' reports of treatment-emergent adverse events
      and by review of laboratory test results. Acarbose was safe and effective in
      improving glycemic control in patients with type 2 diabetes, regardless of their
      age, weight, ethnic background, time since diagnosis, or concomitant sulfonylurea
      therapy. Hb A1c levels declined throughout the treatment period, for a mean
      change in Hb A1c of -0.66%. The mean change from baseline in 1-hour PPG levels
      was -41 mg/dL at the end of treatment. Although all types of patients enrolled in
      the study responded positively to acarbose therapy, certain subgroups responded
      particularly well, especially those who had been diagnosed with the disease for
      less than 1 year and those who were untreated at study entry. Adverse events
      consisted primarily of gastrointestinal disturbances.

PMID- 9589818
TI  - Salmeterol powder compared with albuterol aerosol as maintenance therapy for
      asthma in adolescent and adult patients.
AB  - Two multicenter, randomized, double-masked, placebo-controlled studies involving
      451 adolescent and adult patients with mild-to-moderate asthma compared the
      efficacy and safety of salmeterol powder 50 micrograms twice daily with albuterol
      180 micrograms four times daily or placebo (with albuterol as needed) for 12
      weeks. Patients had forced expiratory volume in 1 second (FEV1) of 50% to 80%.
      Throughout the 12-week treatment period, the mean change from baseline in
      percentage of predicted FEV1 was significantly greater with salmeterol than with
      placebo; mean area under the curve for FEV1 was significantly greater with
      salmeterol than with albuterol or placebo. Significant improvements in morning
      and evening peak expiratory flow, percentage of nights without awakening, and
      asthma symptoms were observed with salmeterol. Salmeterol was well tolerated, and
      no clinically significant changes in electrocardiographic activity were observed.

PMID- 9589819
TI  - Mometasone furoate 0.1%-salicylic acid 5% ointment versus mometasone furoate 0.1%
      ointment in the treatment of moderate-to-severe psoriasis: a multicenter study.
AB  - Topical corticosteroids and keratolytics are both used widely in the management
      of patients with psoriasis. A combination of the two types of agents may provide
      enhanced relief. The purpose of this study was to compare the efficacy and safety
      of the combination ointment mometasone furoate 0.1% plus salicylic acid 5% with
      that of mometasone furoate 0.1% ointment in the treatment of moderate-to-severe
      psoriasis vulgaris. A total of 408 patients were enrolled in this controlled,
      randomized, double-masked, parallel-group, multicenter comparison. Patients
      applied either mometasone furoate-salicylic acid ointment or mometasone furoate
      ointment alone to target lesions twice daily for 21 days. Severity of erythema,
      induration, and scaling were scored at baseline and at days 4, 8, 15, and 22. An
      evaluation of overall change in disease status of all treated lesions was
      performed at each follow-up visit. Adverse events were also monitored and scored,
      including signs of skin atrophy. Beginning on day 8, the combination of
      mometasone furoate-salicylic acid was significantly more effective than
      mometasone furoate alone, as indicated by the mean percentage of improvement in
      total disease scores, mean total disease sign scores, and the individual score
      for scaling. Similarly, the combination was more effective beginning on day 15,
      as indicated by the global evaluation of overall clinical response and individual
      scores for erythema and induration. Both treatments were well tolerated.
      Mometasone furoate-salicylic acid ointment provides more effective treatment of
      moderate-to-severe psoriasis than does mometasone furoate ointment alone and is
      safe and well tolerated.

PMID- 9589820
TI  - Pharmacokinetic profile of cisapride 20 mg after once- and twice-daily dosing.
AB  - Cisapride is a substituted piperidinyl benzamide. It is chemically related to
      metoclopramide but lacks the antidopaminergic properties of metoclopramide that
      affect the central nervous system and cause extrapyramidal side effects.
      Cisapride is indicated for the symptomatic treatment of patients with nocturnal
      heartburn due to gastroesophageal reflux disease. Based on extensive assessment
      of the drug's pharmacokinetic profile, the currently approved initial oral dosing
      regimen for cisapride is 10 mg QID. However, the pharmacokinetics of cisapride
      after oral administration of 20 mg BID have not been investigated. We present
      here findings from an open-label trial assessing the pharmacokinetics of
      cisapride 20-mg tablets after a single dose and at steady state (BID dosing). The
      results indicate that 20-mg BID and 10-mg QID regimens produce similar steady
      state concentrations.

PMID- 9589821
TI  - Use of topical corticosteroid pretreatment to reduce the incidence and severity
      of skin reactions associated with testosterone transdermal therapy.
AB  - Local skin reactions at the application site are the most common adverse events
      associated with the testosterone transdermal delivery (TTD) systems used to treat
      postpubertal hypogonadism in males. This open-label, controlled pilot study was
      conducted to determine whether topical pretreatment with triamcinolone acetonide
      0.1% cream might be useful in reducing the incidence and/or severity of chronic
      skin irritation when used in healthy volunteers receiving TTD systems. Adult male
      volunteers wore three topical systems, which were applied to the upper back daily
      (Monday through Friday) for 6 weeks: (1) TTD with no pretreatment of application
      site; (2) TTD with pretreatment of application site using triamcinolone acetonide
      0.1% cream; and (3) an inactive occlusive dressing (control). On Monday through
      Thursday, systems were removed 24 hours after application. Patches applied on
      Friday were worn continuously for 72 hours until their removal on Monday. Skin
      reactions were graded on a scale from 0 to 4 (0 = none, 4 = severe) and were
      assessed daily by research personnel, beginning at the time of system removal
      (assessment 1) and on the two subsequent clinic visits (assessments 2 and 3). All
      skin irritation scores of all subjects were totaled for each treatment regimen to
      obtain a cumulative score per treatment regimen. The cumulative scores were also
      analyzed by assessment time and study week (weeks 1-6). Eighty-two subjects were
      enrolled in the study, and 65 completed the 6-week treatment course. Mean age of
      subjects was 24 years (range, 18-69 years), and mean weight was 79.0 kg (range,
      58.9-127.3 kg). All subjects were white males. At assessment 1, pretreatment with
      triamcinolone acetonide 0.1% cream (compared with no pretreatment) was associated
      more often with scores of 0 (no erythema), with comparable occurrences of mild
      skin irritation, and with fewer occurrences of moderate erythema. At all three
      assessments, more subjects had lower cumulative scores with pretreatment than
      without pretreatment. At every assessment and in each week of the study, total
      weekly cumulative skin irritation scores were also lower with pretreatment than
      without pretreatment. No adverse experiences other than skin irritation were
      reported. Results of this study suggest that in patients using TTD systems, the
      incidence and severity of skin irritation at application sites may be reduced
      through pretreatment with triamcinolone acetonide 0.1% cream.

PMID- 9589822
TI  - Disposition of 14C-eptifibatide after intravenous administration to healthy men.
AB  - Eptifibatide, a synthetic peptide inhibitor of the platelet glycoprotein IIb/IIIa
      receptor, has been studied as an antithrombotic agent in a variety of acute
      ischemic coronary syndromes. The purpose of the present study was to characterize
      the disposition of 14C-eptifibatide in man after a single intravenous (i.v.)
      bolus dose. 14C-Eptifibatide (approximately 50 microCi) was administered to eight
      healthy men as a single 135-microgram/kg i.v. bolus. Blood, breath carbon
      dioxide, urine, and fecal samples were collected for up to 72 hours postdose and
      analyzed for radioactivity by liquid scintillation spectrometry. Plasma and urine
      samples were also assayed by liquid chromatography with mass spectrometry for
      eptifibatide and deamidated eptifibatide (DE). Mean (+/- SD) peak plasma
      eptifibatide concentrations of 879 +/- 251 ng/mL were achieved at the first
      sampling time (5 minutes), and concentrations then generally declined
      biexponentially, with a mean distribution half-life of 5 +/- 2.5 minutes and a
      mean terminal elimination half-life of 1.13 +/- 0.17 hours. Plasma eptifibatide
      concentrations and radioactivity declined in parallel, with most of the
      radioactivity (82.4%) attributed to eptifibatide. A total of approximately 73% of
      administered radioactivity was recovered in the 72-hour period following 14C
      eptifibatide dosing. The primary route of elimination was urinary (98% of the
      total recovered radioactivity), whereas fecal (1.5%) and breath (0.8%) excretion
      was small. Eptifibatide is cleared by both renal and nonrenal mechanisms, with
      renal clearance accounting for approximately 40% of total body clearance. Within
      the first 24 hours, the drug is primarily excreted in the urine as unmodified
      eptifibatide (34%), DE (19%), and more polar metabolites (13%).

PMID- 9589823
TI  - Implementing disease management in community pharmacy practice.
AB  - Disease management (DM) is a comprehensive approach to preventing and treating
      disease that: (1) targets patients with specific diseases; (2) provides
      integrated services across organizational and professional boundaries; (3)
      utilizes services based on the best scientific evidence available; and (4)
      focuses on outcomes. DM differs from pharmaceutical care in that pharmaceutical
      care targets not only patients with specific diseases but also those with risk
      factors for drug-related problems, a history of nonadherence, and frequent
      changes in medication regimens. Steps to starting a DM program include: (1)
      identifying a target population based on the population's strategic importance to
      the goals and aims of the organization; (2) assessing the organization's
      available resources, both internal and external; (3) defining key indicators with
      which to assess the program for the purposes of internal quality control and of
      obtaining compensation from third-party payers; (4) implementing the program
      using the best scientific methods available; and (5) assessing the impact of the
      program. The development of a smoking cessation program at a nationwide retail
      pharmacy chain is used as an example of a DM program initiated in community
      pharmacy practice. Pharmacists are well positioned to take a major role in DM,
      because they are accessible to the community and because DM frequently involves
      drug therapy. DM is also widely used in managed care. It is important that
      community pharmacists be closely involved in the DM approach as it evolves.

PMID- 9589825
TI  - Cost analysis of ardeparin versus enoxaparin for the prophylaxis of deep vein
      thrombosis after knee arthroplasty.
AB  - Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications
      associated with total knee arthroplasty. The American College of Chest Physicians
      recommends twice-daily, fixed-dose low-molecular-weight heparin (LMWH) as routine
      prophylaxis in this patient population. This study represents a cost analysis of
      ardeparin and enoxaparin, the two LMWHs currently available for this indication
      in the United States. Costs for treating DVT, PE, and major bleeding episodes
      were derived from values reported in the literature. Both ardeparin and
      enoxaparin were found to produce significant cost savings when used routinely as
      DVT prophylaxis after knee replacement surgery compared with no prophylaxis.
      Based on the currently available data, enoxaparin 40 mg once daily appears to be
      the least costly LMWH for routine pharmacoprophylaxis of DVT in patients
      undergoing knee replacement surgery.

PMID- 9589824
TI  - Conversion from fluvastatin to simvastatin therapy at a dose ratio of 8 to 1:
      effect on serum lipid levels and cost.
AB  - The objective of this study was to assess the effect on serum lipid levels of the
      substitution of simvastatin for fluvastatin at a dose ratio of 8:1 (fluvastatin
      to simvastatin). A secondary objective was to determine the number of patients at
      goal lipid levels before and after this substitution. The study included 60
      outpatients with hyperlipidemia who had received a constant dose of fluvastatin
      for at least 6 weeks. After a baseline 12-hour lipid profile (total cholesterol,
      triglycerides, high-density lipoprotein, and low-density lipoprotein [LDL]) was
      obtained, patients were switched from fluvastatin to simvastatin at an 8:1 dose
      ratio. Patients were instructed to split the simvastatin tablets in half with a
      pill splitter and to take one half-tablet at bedtime. A repeat lipid profile and
      liver function testing were performed after 6 to 8 weeks of simvastatin therapy.
      Lipid components were compared before and during simvastatin therapy using a
      paired t test. Target LDL levels were based on guidelines issued by the National
      Cholesterol Education Program. Fifty-six patients completed the study. No change
      in lipid components was observed, except for a statistically significant decrease
      in LDL. The majority of patients had a decrease in LDL levels, rather than an
      increase, after the conversion to simvastatin. Six patients required a dose
      increase of simvastatin in response to increased LDL levels. Forty-one percent of
      patients achieved goal LDL levels with simvastatin, compared with 30% with
      fluvastatin. Four patients withdrew from the study, two because of troublesome
      side effects and two for failure to complete the protocol. The results show that
      simvastatin can be substituted for fluvastatin at a dose ratio of 8:1 without
      loss of lipid control in the majority of patients and that by using this ratio
      and splitting tablets, significant cost savings can be realized.

PMID- 9589826
TI  - Effects of risperidone therapy on the use of mental health care resources in Salt
      Lake County, Utah.
AB  - The authors analyze the use of mental health care resources before and after the
      initiation of risperidone therapy in patients of Valley Mental Health, an agency
      providing aggressive community-based treatment in Salt Lake County, Utah. Sixty
      three patients were treated with risperidone during the period from February 1994
      through June 1995. Data for at least 6 months before (pre-period) and after (post
      period) risperidone therapy were available for 61 patients; the mean period for
      which data were obtained was 31.8 months (pre- plus post-period). Risperidone use
      was associated with a reduction, albeit nonsignificant, in the numbers of
      patients requiring acute inpatient hospital care (-29%), days hospitalized (-1
      day per year), residential treatment days (-0.7 days per year), and day-treatment
      visits (-1.7 visits per year), together with small increases, also
      nonsignificant, in the need for emergency/crisis intervention (0.1 visit per
      year), outpatient treatment (0.1 visit per year), and case management (2.3 visits
      per year). The costs of institutional plus ambulatory care declined from $7949 to
      $6910 per patient per year (-13%); the greatest reduction was in the cost of
      acute inpatient care (-18%). With the addition of risperidone, the cost of
      psychotropic medications doubled, resulting in a statistically nonsignificant
      mean increase in total costs of $305 per patient per year. Among the 36 patients
      who received risperidone during > or = 70% of the post-period and the 17 patients
      who had been hospitalized during the pre-period, total costs declined -3% and 
      13%, respectively. The results confirm those of previous studies and demonstrate
      that risperidone can reduce the use of mental health services.

PMID- 9589827
TI  - Sedative effects of antihistamines: safety, performance, learning, and quality of
      life.

PMID- 9589829
TI  - Antiplatelet therapy in atherosclerotic cardiovascular disease.
AB  - Arterial thrombosis frequently leads to death or disability from stroke,
      peripheral arterial disease, or myocardial infarction (MI). Treating the
      underlying causes of these diseases is the key to producing significant reduction
      in morbidity, mortality, and health care costs. Prevention of arterial thrombosis
      is the primary indication for antiplatelet therapy, and intense research has been
      conducted in the past decade to develop novel antiplatelet agents with favorable
      safety profiles. The results of the Antiplatelet Trialists' Collaboration, which
      definitively established the rationale for antiplatelet agents in the prevention
      of death, MI, and stroke, were an important stimulus for this research. This
      large meta-analysis combined data from 145 randomized trials and showed that
      antiplatelet therapy (most commonly aspirin, 75 to 325 mg/d) reduced the risk of
      vascular events, including nonfatal MI, nonfatal stroke, and vascular death, by
      25% in patients at high risk for occlusive vascular disease. The limitations and
      adverse effects associated with traditional antiplatelet agents such as aspirin
      have prompted the search for newer antiplatelet agents. Clinical trials such as
      the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE)
      study, which was the first study to evaluate aspirin and clopidogrel in patients
      with cerebrovascular, cardiac, and peripheral arterial disease, have established
      the importance of newer antiplatelet effects in the management of patients with
      diseases associated with atherosclerosis. The pathophysiology of atherosclerosis,
      the mechanisms of action of antiplatelet agents, and the results of these and
      other clinical trials that document the value of antiplatelet agents in
      atherosclerosis are reviewed in this paper.

PMID- 9589828
TI  - Overview of atherosclerosis.
AB  - Cardiovascular disease is a serious threat to both life and health, accounting
      for 44% of the nation's mortality and much of its morbidity. Moreover,
      atherosclerotic cardiovascular disease is a growing problem because of the aging
      population. Coronary heart disease is the most common cause of lethal
      atherosclerotic disease, accounting for two thirds of all deaths resulting from
      heart disease and 70% of all deaths in those older than 75. A 1997 estimate put
      the economic cost of atherosclerotic cardiovascular disease at a staggering $259
      billion. Indications are that atherosclerotic cardiovascular disease is a
      generalized process that involves the heart, brain, and peripheral arteries.
      Clinical manifestations tend to coexist, and the presence of one manifestation
      increases the likelihood of developing others, because major risk factors tend to
      affect all arterial territories. Also, clinical atherosclerosis in one area may
      directly predispose the patient to occurrence of atherosclerosis in another
      vascular territory. Therefore, measures taken to prevent one clinical
      manifestation of atherosclerosis should prevent the others as well. Multivariate
      risk profiles can identify persons at risk for atherosclerotic cardiovascular
      disease and target them for preventive treatment. Primary preventive measures
      also appear to be applicable to secondary prevention. Meta-analyses of randomized
      trials of the efficacy of low-dose aspirin and other antiplatelet agents in
      persons with overt cardiovascular disease have shown reductions of approximately
      25% in the incidences of subsequent myocardial infarctions, strokes, and
      cardiovascular mortality. Comparison of the risk profiles for atherosclerotic
      cardiovascular disease indicates that correction of any particular set of risk
      factors or prevention of any cardiovascular disease outcome prevents other
      atherosclerotic disease outcomes as well. The challenge for all health care
      professionals is to implement comprehensive preventive measures for those at high
      risk for initial atherosclerotic events and even more vigorous measures for those
      who already have the disease.

PMID- 9589830
TI  - Clinical safety and efficacy of clopidogrel--implications of the Clopidogrel
      versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study for future
      management of atherosclerotic disease.

PMID- 9589831
TI  - The risks of venous thromboembolic disease among German women using oral
      contraceptives: a database study.
AB  - This study investigated the risk of venous thromboembolic disease (VTE) between
      second and third generation combined oral contraceptives, using the German
      MediPlus database of patient records. Women studied included 42 patients between
      the ages of 18 and 49 years, with a diagnosis of VTE treated with an
      anticoagulant, who were exposed to an oral contraceptive (OC). Four controls per
      patient (168), matched by year of birth and exposure to an OC on the even day,
      were identified. More women were users of second generation than third generation
      OC, and none were using progestogen-only pills. There was no significant
      difference between patients and control subjects with respect to the type of OC
      used on the event day (unadjusted odds ratio for third versus second generation
      users was 0.77; 95% confidence interval [CI] 0.38-1.57). There was no significant
      age difference between second and third generation users among patients or
      control subjects. Between January 1 and the event date, there was no significant
      difference between the patients and control subjects in terms of the number of
      oral contraceptive prescriptions, number of consultations for psychotherapeutic
      complaints, or mixed physical and psychotherapeutic consultations; however,
      patients did demonstrate significantly more consultations for purely physical
      complaints compared with control subjects (p < 0.0001). There were no significant
      consultation differences between patients with pulmonary emboli (n = 6) and other
      VTE patients (n = 36). No significant differences with respect to VTE risk
      between users of second and third generation oral contraceptives were found in
      this study. Consultations (physical) for patients were higher than for control
      subjects before the VTE event. If consultation rate relates to the general health
      status of a person, this might indicate that VTE risk is higher among women of
      poorer health, but that this is not related to the type of progestogen in the
      oral contraceptive that they use.

PMID- 9589832
TI  - Comparative study of the effects of two once-a-month injectable steroidal
      contraceptives (Mesigyna and Cyclofem) on glucose metabolism and liver function.
      United Nations Development Programme/United Population Fund/World Health
      Organization/World Bank, Special Programme of Research, Development and Research
      Training in Human Reproduction, Task Force on Long-acting Systemic Agents for
      Fertility Regulation.
AB  - A 1-year, longitudinal, multicenter study was undertaken to monitor the effects
      of two once-a-month, injectable contraceptive preparations, Mesigyna
      (norethisterone enanthate, 50 mg, and estradiol valerate, 5 mg) and Cyclofem
      (medroxyprogesterone acetate, 25 mg, and estradiol cypionate, 5 mg) on
      carbohydrate metabolism and liver function. A total of 357 volunteers from four
      centers (Hangzhou, Havana, Jakarta, and Shanghai) were monitored during one
      pretreatment cycle, at the end of the ninth injection interval and during one
      posttreatment cycle, approximately 3 months after the 9-month period of treatment
      was completed. Both preparations induced minor changes in glucose tolerance, with
      a slight elevation of glucose response and minimal changes in insulin response to
      a glucose challenge. These changes were greater with Mesigyna but were of no
      clinical relevance in either group. With regard to liver function, both
      preparations induced a rise in bilirubin, a decrease in alkaline phosphatase, and
      no change in enzyme serum levels. However, these changes were of small magnitude
      and levels remained well within the normal range in all subjects.

PMID- 9589833
TI  - Oral methotrexate and vaginal misoprostol for early abortion.
AB  - A prospective trial including 300 pregnant women seeking elective abortion was
      conducted to evaluate the safety and efficacy of methotrexate and misoprostol for
      abortion at < or = 63 days' gestation. Subjects received methotrexate 50 mg
      orally and were randomly allocated to receive 800 micrograms of misoprostol
      vaginally 3, 4, or 5 days after administration of the methotrexate. The
      misoprostol dose was repeated 48 and 96 h later if abortion did not occur.
      Outcome measures included successful abortion (complete abortion without
      requiring a surgical procedure) and side effects. Complete abortion occurred in
      273 of 300 patients (91%, 95%, CI 87, 94%) patients. No significant statistical
      differences were found in the success rates when misoprostol was given days 3, 4,
      or 5 after the administration of methotrexate (p = 0.69). Vaginal bleeding lasted
      7.1 +/- 3.8 days, spotting 4.1 +/- 2.5 days, and total bleeding 11.2 +/- 4.1
      days. Side effects for methotrexate were minimal, whereas, for misoprostol they
      were mild and transient except for pain. The use of methotrexate and misoprostol
      together could be an alternative to the intramuscular use of methotrexate or the
      use of antiprogestins and prostaglandin for medical abortion.

PMID- 9589834
TI  - Pilot study on the use of a two-week course of oral misoprostol in patients after
      termination of pregnancy with mifepristone and misoprostol.
AB  - Twenty women who requested early first trimester termination of pregnancy were
      recruited to study the tolerability of a 2-week course of oral misoprostol after
      termination of pregnancy by mifepristone and vaginal misoprostol. Ten patients
      (50%) complained of mild diarrhea during the 2-week course of misoprostol.
      Otherwise, there were no other significant side effects. The 2-week course of
      misoprostol was well tolerated by women who underwent early first trimester
      termination of pregnancy with mifepristone and misoprostol.

PMID- 9589835
TI  - Prevalence and clinical correlates of unsuccessful use of drugs to induce
      menstruation.
AB  - Despite its prohibition, illegal abortion is widely practiced in Brazil, with
      important adverse health consequences. This report aims to document the
      prevalence and correlates of the unsuccessful use of drugs to "induce menstrual
      flow" in a cohort of pregnant Brazilian women. In a cross-sectional study, 6,102
      pregnant women between gestation weeks 21 and 28 were interviewed in prenatal
      clinics of the Brazilian National Health Care System from April 1991 to November
      1995. When asked "In order to know if you were pregnant, did you take any
      medication to induce menstrual flow", 874 (14.4%) responded "yes." The most
      frequently used drugs were herbal teas (41%), estrogens and/or progestogens
      (30%), and misoprostol (16%). As demonstrated through logistic regression
      analysis, independent correlates of such use were unplanned pregnancy (odds ratio
      [OR] 4.3), low educational attainment (OR 3.3), absence of a husband or partner
      (OR 1.8), number of children (one or more) (OR 1.5), a history of a previous
      induced abortion (OR 1.4), and use of oral contraceptives at the time (OR 1.4).
      Misoprostol use occurred in 2.2% of pregnancies, and showed a very strong
      association with an unplanned pregnancy (OR 16.0), absence of a husband or
      partner (OR 3.5), and a history of a previous induced abortion (OR 2.2). It was
      not associated with a history of menstrual irregularity. In contradistinction,
      the use of medroxyprogesterone was strongly associated with previous menstrual
      irregularity (OR = 5.0). The use of drugs and teas, many of which are unknown in
      terms of fetal risk, in early pregnancy to induce menstrual flow is quite common
      in women in the Brazilian National Health System. Although the objective of such
      drug use appears to be varied, analysis of the clinical correlates of use suggest
      attempted abortion to be the principal aim.

PMID- 9589836
TI  - Ulnar nerve injury associated with removal of Norplant implants.
AB  - Improperly placed Norplant implants pose a risk to neurovascular structures at
      the time of removal. Appropriate attention to insertion and removal should
      minimize the chance of injury. However, when injuries do occur, a logical and
      systematic approach to evaluation of the injury can help predict the outcome and
      establish a plan of care for the patient.

PMID- 9589837
TI  - Efficacy and safety of the new antiandrogenic oral contraceptive Belara.
AB  - The aim of this open, noncontrolled phase III study was the assessment of the
      contraceptive efficacy and the evaluation of the safety of long-term use of
      Belara (30 micrograms ethinyl estradiol plus 2 mg chlormadinone acetate).
      Furthermore, cycle stability during administration of Belara and the influence of
      Belara on acne and seborrhea as clinical signs of androgenization were observed.
      Belara was taken by 1655 women for a total of 22,337 cycles. For the theoretical
      Pearl index, a value of 0.269 (95% CI [0.109, 0.600]) was calculated. In 1655 of
      22,337 cycles (7.4%), no withdrawal bleeding was documented, whereas in 2565 of
      22,308 cycles (11.5%), spottings and, in 786 of 22,308 cycles (3.5%),
      breakthrough bleeding occurred. After the intake of Belara for 12 cycles, acne on
      the face/neck improved in 64.1% of the women (209 of 326). In 53.4% of the women
      (175 of 326), acne disappeared completely. Seborrhea improved after 12 cycles in
      89 of 131 women (67.9%), of whom 76 women (58.0%) were completely cured. Sixty
      two serious adverse events (SAE) occurred in 59 of 1655 women. Accidents and
      injuries of the musculoskeletal system were the SAE with the highest incidence
      (0.66%). Two cases of deep venous thrombosis, one pulmonary embolism, and two
      cases of visual disturbances were observed. Only for the two cases of deep venous
      thrombosis could a relation to Belara be assumed. Of the adverse events commonly
      reported for oral contraceptives, headache was observed for the first time under
      study medication in 37.4%, nausea in 23.1%, breast tenderness in 21.7%, and
      vaginal discharge in 19.4% of the women. The frequency of adverse events
      decreased with longer duration of a drug consisting of intake of Belara. In
      conclusion, Belara can be described as an effective and safe oral contraceptive
      with marked antiandrogenic properties.

PMID- 9589838
TI  - Diffusion of nonoxynol-9 into human semen in vitro.
AB  - The diffusion of [125I]-nonoxynol-9 into human semen was investigated in vitro
      before and after liquefaction. No significant difference was found in the
      distribution of [125I]-nonoxynol-9 within columns of preliquefied semen,
      liquefied semen, seminal plasma, or water after < or = 120 minutes of diffusion;
      however, significantly more nonoxynol-9 entered preliquefied semen. The
      concentration of nonoxynol-9 that entered semen in vitro was greater than its
      ED100 and the bioavailability was confirmed by demonstration of the retention of
      spermicidal action. These results indicate that the gel state of preliquefied
      semen does not inhibit the entry or action of nonoxynol-9 and, consequently,
      sperm would be exposed to it immediately when it is used in vivo as a vaginal
      spermicide.

PMID- 9589839
TI  - Biphasic c-Myc protein expression during gossypol-induced apoptosis in rat
      spermatocytes.
AB  - The presence of protooncogene products such as c-Myc proteins in rat
      spermatocytes has been quantitatively detected by Western immunoblot and a
      computer-controlled Spotdenso-program with an IS-1000 digital imaging system.
      Cellular levels of c-Myc proteins in response to gossypol were measured in
      spermatocytes during the process of gossypol-induced apoptosis. Within 0.5 to 2 h
      of the addition of gossypol, levels of c-Myc proteins fall dramatically and
      remain at a low level for the next several hours. The reduction in c-Myc proteins
      occurs 4.5-6 h before the apoptosis of spermatocytes in the presence of gossypol.
      Between 3 and 5 h after exposure to gossypol, the c-Myc protein content returns
      to preexposure (or higher) levels. In addition, the increase in c-Myc proteins
      occurs 1.5-4 h before the apoptotic death of spermatocytes. An identical pattern
      of c-Myc protein response to gossypol was also found in total testicular tissue
      in vitro. These results suggest that spermatocyte apoptosis induced by gossypol
      is correlated with biphasic c-Myc protein expression. This article present some
      hypothetical models with which to explain c-Myc protein-mediated apoptosis.

PMID- 9589841
TI  - High-resolution MR cholangiopancreatography.
AB  - 1. High-resolution MRCP is a noninvasive imaging modality for depicting the
      pancreatobiliary tree. The imaging quality of high-resolution MRCP is
      satisfactory. MRCP can demonstrate dilation, stenosis, and intraductal filling
      defects of both the biliary tract and the pancreatic duct, which meets the
      clinical demand for pancreatobiliary imaging. 2. MRCP was successful in almost
      all the patients. However, the causes of MRCP failure were patient motion,
      irregular respiratory rhythm, severe pneumobilia, and massive ascitic fluid. 3.
      When only MIP reconstructed images were used for interpretation, small
      intraductal filling defects such as a gallstone can be missed. In combination
      with coronal source images, the ability to detect intraductal stones can be
      increased. 4. Ferrite ammonium citrate (FAC) is useful in suppressing the
      background signal intensity of gastrointestinal contents so that the ducts can be
      clearly visualized. The other technique for decreasing the background signal
      intensity is target MIP postprocessing, which works well for better visualization
      of the ducts. 5. The degree of ductal narrowing tends to be overestimated with
      MRCP because of MIP reconstruction artifact and lower spatial resolution of MRCP
      than ERCP. 6. MRCP has a diagnostic pitfall of a pseudostenosis of extrahepatic
      ducts, which may lead to a false-positive diagnosis of ductal narrowing. This
      pitfall may be caused not only by MIP postprocessing artifacts but by gas,
      surgical metal, and vascular compression of right hepatic artery. There is
      another diagnostic pitfall that it is difficult to differentiate intraductal
      mucin from pancreatic fluid in dilate pancreatic ducts, although ERCP identifies
      mucin as intraductal filling defects.

PMID- 9589840
TI  - Ultrastructural changes in the spermatozoa of langur monkeys Presbytis entellus
      entellus after vas occlusion with styrene maleic anhydride.
AB  - Changes in the physical characteristics of semen and ultrastructure of the
      spermatozoa of langur monkeys after vas occlusion with styrene maleic anhydride
      (SMA), a polymer with pH-lowering action, are reported. Vas occlusion resulted in
      severe reversible hypospermia. Severe oligospermia was observed in the majority
      of animals (five of eight) in the first ejaculation, 30 days after vas occlusion,
      and in two animals in the second ejaculation, 60 days after vas occlusion.
      Subsequent monthly ejaculations for 5 months revealed uniform azoospermia. The
      voided spermatozoa were immotile and supravital staining confirmed necrospermia.
      Scanning electron microscopy (SEM) revealed severe coiling of tail, rupture of
      acrosomal envelope, and bent midpiece associated with damaged mitochondrial
      sheath. Observations by transmission electron microscopy (TEM) revealed
      vacuolization in the nucleus, membrane damage in the acrosome, loss of segmented
      columns, and numeric aberrations in the centriole of the neck, as well as
      degeneration of mitochondrial sheath and axoneme in the midpiece, and absence of
      outer plasma membrane in the midpiece and tail. The results indicate that the
      necrospermic status of the spermatozoa during initial ejaculations may offer
      instant sterility after vas occlusion with SMA.

PMID- 9589842
TI  - Mitral valve regurgitation.

PMID- 9589843
TI  - Evaluation of the carcinogenic potential of pharmaceuticals. Opportunities
      arising from the International Conference on Harmonisation.
AB  - The evaluation of the carcinogenic potential of pharmaceuticals is currently
      undergoing dramatic changes. For the past 25 years the regulatory expectation for
      agents intended for long term use has been that lifespan studies (usually lasting
      2 years) in 2 rodent species be conducted. These studies take at least 3 years to
      plan, execute and interpret, and use over 1200 animals. It is now recognised that
      the quality of the information obtained from these studies is unreliable for
      prediction of carcinogenic risk to humans. Over the past 4 years, the
      International Conference on Harmonisation (ICH) has recommended changes in
      approaches to assessing the carcinogenic potential of pharmaceuticals. In future,
      only one long term rodent study will be routinely required (usually in rats),
      provided this is complemented with a short or medium term test in one of the
      emerging new models for carcinogenicity, such as transgenic mice or newborn mice.
      However, the relevance of these new models to human cancer and their use in risk
      assessment is still largely unknown and this situation must be kept under review
      as knowledge accumulates. A long term study in a second rodent species is still
      an option. Dose selection has also been improved inasmuch as there are now
      several alternatives to the use of the maximum tolerated dose (MTD). In the past,
      the use of the MTD, when the normal homeostasis of the test animals is disturbed,
      has been considered one of the major problems with the rodent carcinogenicity
      bioassay. However, one of the alternative end-points to the use of the MTD, i.e.
      the comparison of plasma concentrations in rodents and humans, must be viewed
      with caution. While this may contribute to limiting the high dose level for
      agents of very low toxicity, the concept should not be interpreted as signifying
      that plasma concentrations provide a sound basis for comparing the carcinogenic
      activity of agents in different species. Recognition of the 4 properties
      (genotoxicity, immunosuppression, steroid hormonal activity and long term tissue
      damage), at least one of which is associated with each of the pharmaceuticals
      known to be carcinogenic to humans, should focus more attention on a search for
      these properties in patients. Absence of these properties at clinically relevant
      dose levels indicates that a pharmaceutical is highly unlikely to be carcinogenic
      to humans.

PMID- 9589845
TI  - Amiodarone-induced pulmonary toxicity. Predisposing factors, clinical symptoms
      and treatment.
AB  - Amiodarone is frequently used for the treatment of cardiac arrhythmias. Although
      the therapeutic efficacy of amiodarone has been established, its use is limited
      by its safety profile. Amiodarone-induced pulmonary toxicity is one of the most
      life-threatening complications of this therapy. It is a relatively rare adverse
      effect of amiodarone and is easily missed by any physician who is suddenly
      confronted with nonspecific pulmonary complaints during amiodarone treatment.
      There are several cumulative factors which may enhance the susceptibility of
      patients for amiodarone-induced pulmonary toxicity, such as advanced age and pre
      existing pulmonary dysfunction. Several case studies and clinical trials of
      amiodarone have shown the possible occurrence of amiodarone-induced pulmonary
      toxicity during low dose and short-duration therapy. Therefore, the dose and
      duration of amiodarone treatment are not the only determinants of toxicity risk.
      Amiodarone-induced pulmonary toxicity is characterised by various clinical
      manifestations such as coughing, dyspnoea, fever, bodyweight loss, respiration
      related chest pain and bilateral lung infiltrates with no excavated nodules. Once
      amiodarone-induced pulmonary toxicity has been diagnosed, therapeutic options are
      limited, but in most cases the disease is reversible, if diagnosed at an early
      stage.

PMID- 9589846
TI  - Safety issues in the treatment of paediatric supraventricular tachycardias.
AB  - Paroxysmal supraventricular tachycardia caused by atrioventricular re-entry is
      the most frequent arrhythmia in children of all age groups. It represents the
      most frequent clinical situation where antiarrhythmic drug therapy has to be
      considered in a child. Acute termination of an episode of tachycardia in all
      paediatric age groups is nowadays best achieved with an intravenous bolus
      injection of adenosine. Since the introduction of adenosine into clinical
      practice, the need to proceed to electrocardioversion has been limited to the
      infant (or in rare cases an older child) with severe cardiovascular collapse. In
      the haemodynamically stable infant or child, several other antiarrhythmic agents
      such as flecainide or propafenone can be used with relative safety and with a
      high probability of immediate success. The same is true for verapamil, although
      intravenous administration should be avoided in the first year of life. In
      newborns and in infants with first presentation of an episode of tachycardia,
      drug prophylaxis of recurrences is usually recommended for the whole of the first
      year of life. Prophylactic treatment may consist of oral digoxin as first choice,
      with a beta-blocker as an alternative. In an infant with Wolff-Parkinson-White
      syndrome it may be wise to avoid digoxin and to start treatment with a beta
      blocker. Antiarrhythmic class Ic drugs such as propafenone or flecainide, and the
      class III agent sotalol, are widely used as the next steps of therapy when
      digoxin and beta-blockers fail to prevent recurrences. These agents are about
      equivalent with regard to their efficacy and risk profile. Amiodarone is
      considered to be an agent that should be reserved for use in situations when the
      tachycardia is refractory to the previously named agents. Older children may
      commence treatment with a beta-blocker and the subsequent steps of treatment are
      the same as those for infants. Curative catheter ablation of accessory pathways
      has been shown to be as efficient and well tolerated in the paediatric age group
      as it is in adults. This treatment option is nowadays quite often offered to
      older children. However, in infants and smaller children, ablation is used as a
      last resort. Rare forms of paediatric supraventricular tachycardia (other than
      atrioventricular re-entry through the atrioventricular node or accessory
      pathways) are occasionally difficult to treat and present special problems. For
      each of these arrhythmias, a specially tailored individual therapeutic approach
      is needed.

PMID- 9589844
TI  - A risk-benefit assessment of natural and synthetic exogenous surfactants in the
      management of neonatal respiratory distress syndrome.
AB  - Alveolar surfactant is central to pulmonary physiology. Quantitative and
      qualitative surfactant abnormalities appear to be the primary aetiological
      factors in neonatal respiratory distress syndrome (RDS) and exogenous replacement
      of surfactant is a rational treatment. Available exogenous surfactants have a
      natural (mammal-derived lung surfactants) or synthetic origin. Pharmacodynamic
      and clinical studies have demonstrated that exogenous surfactants immediately
      improve pulmonary distensibility and gas exchange; however, this is achieved more
      slowly and with more failures with synthetic surfactants. The ensuing
      advantageous haemodynamic effects are not so striking and they include an
      inconvenient increased left to right ductal shunt. Two strategies of
      administration have been used: prophylactic or rescue therapy to treat declared
      RDS. All methods of instillation require intubation. In addition to the early
      benefits (improved gas exchange and reduced ventilatory support) the incidence of
      classical complications of RDS, especially air leak events, is decreased except
      for the uncommon problem of pulmonary haemorrhage. The incidence of
      bronchopulmonary dysplasia is neither uniformly nor significantly reduced
      although the severity appears to be lessened. The overall incidence of peri
      intraventricular haemorrhages is not diminished although separate trials have
      shown a decreased rate. The most striking beneficial effect of exogenous
      surfactants is the increased survival (of about 40%) of treated very low
      birthweight neonates. A small number of adverse effects has been described. The
      long term outcome of survivor neonates with RDS treated with surfactants versus
      control neonates with RDS not treated with surfactants is similar in terms of
      physical growth, at least as good in terms of respiratory status, with a similar
      or slightly better neurodevelopmental outcome. There is not clear benefit of
      exogenous surfactant therapy in extremely premature infants (< 26 weeks
      gestational age, birthweight < 750 g). The potential risks of contamination,
      inflammatory and immunogenic reaction and the inhalation of platelet activating
      factor remain a theoretical concern of surfactant therapy which has not been
      confirmed in clinical practice. The optimal timing of treatment favours
      prophylaxis over rescue treatment and early rescue treatment rather than delayed
      therapy. Meta-analyses suggest the clinical superiority of natural surfactant
      extracts over a synthetic one (colfosceril palmitate). The economic impact of
      surfactant therapy is favourable and the costs per quality-adjusted life year
      (QALY) for surviving surfactant treated infants are low. In conclusion, the mid
      and long term benefit/risk ratio clearly favours the use of exogenous surfactants
      to prevent or to treat RDS in neonates who have a gestational age of > 26 weeks
      or a birthweight of > 750 g, especially with the prophylactic strategy using
      natural surfactant extracts.

PMID- 9589849
TI  - [Alpha-helix retention in prion proteins].
AB  - Prion diseases belong to a group of neurodegenerative disorders caused by
      conformational changes--destroying the alpha-helices--in prion proteins (PrP). We
      performed a phylogenetic analysis of 32 PrP sequences and restored the most
      probable evolutionary spectrum of amino acid substitutions. Although prion
      proteins are not too conserved judging from the evolutionary rates, conserved
      substitutions leading only to amino acids with similar physical and chemical
      parameters occurred in evolution within the putative helical PrP regions. Those
      substitutions that destroy alpha-helices primarily arose in prion proteins as was
      demonstrated by the methods of prediction of protein secondary structure used for
      analysis of the complete spectrum of single-step substitutions in human PrP
      sequences. The data obtained support a suggestion that prion diseases result from
      changes in PrP conformation manifested in destroying the alpha-helices and
      formation of beta-structures.

PMID- 9589848
TI  - Can the fatal toxicity of antidepressant drugs be predicted with pharmacological
      and toxicological data?
AB  - Antidepressant drugs are among the most common drugs involved in fatal poisoning
      and large variations between antidepressant drugs have been noted. Despite the
      fact that a large number of studies have calculated a fatal toxicity index (FTI)
      for antidepressants, no serious attempts have been made to compare the
      differences in fatal toxicity against known pharmacological and toxicological
      differences in receptor affinity. It is potentially from such data that screening
      of drugs during their pre-clinical development can be facilitated. We examined
      correlations between the FTI and noradrenaline (norepinephrine)/serotonin (5
      hydroxytryptamine; 5-HT) reuptake inhibition selectivity, the dose that is lethal
      to 50% of animals (LD50), lipid solubility, and antagonist activity at
      cholinergic, histaminergic, alpha-adrenergic and gamma-aminobutyric acid (GABA)A
      receptors or sodium and potassium channel blocking effects. We obtained data on
      the number of fatal poisonings between 1983 and 1992 in England and Wales caused
      by a single antidepressant drug from the Department of Health in the UK. This
      number was divided by the number of prescriptions in England for these drugs over
      this time to derive a FTI of deaths per million prescriptions. The highest FTIs
      were for amoxapine, viloxazine, desipramine and dothiepin. Lofepramine,
      paroxetine and fluoxetine had very low FTIs. Using Poisson regression, there was
      a significant positive relationship between the FTI of antidepressant drugs and
      their lethal toxicity in animals, and measures of their cardiac effects. The
      relative noradrenaline/serotonin reuptake inhibition, lipid solubility and their
      potency at histamine H1, muscarinic and alpha 1-adrenergic receptors had no
      substantial association with the FTI. Limited data suggest that some cardiac
      effects and potency as a GABAA antagonist may be important predictors of
      significant toxicity. Further data using standardised bio-assays are needed to
      compare the direct cardiac effects of antidepressants. Thus, the best current pre
      clinical indicator of fatal toxicity in humans is the LD50 in animal studies.
      Clearly, there are humane and practical reasons for developing a better pre
      clinical indicator of toxicity in overdose for this rapidly expanding group of
      drugs.

PMID- 9589850
TI  - [New phenotypic manifestation of the ad2 mutation in Saccharomyces cerevisiae
      yeast--the inability to grow on a synthetic medium with glycerol and
      hypoxanthine].
AB  - The ADE2 gene of Saccharomyces cerevisiae yeast encodes aminoimidazole
      ribonucleotide-carboxylase (AIR-carboxylase), an enzyme catalyzing the sixth
      stage of purine nucleotide biosynthesis. Strains bearing the ade2 mutation are
      able to grow on a glucose-containing synthetic medium with the addition of
      adenine or hypoxanthine, which under the action of the cellular
      phosphoribosyltransferases are converted into adenosine monophosphate and inosine
      monophosphate, respectively. Our studies showed that ade2 mutants were unable to
      grow on a synthetic medium with glycerol and hypoxanthine. This newly described
      feature is not constitutively manifested, because some strains can contain
      suppressor mutations which restore the ability to grow on a synthetic medium with
      glycerol and hypoxanthine. The ade4, ade5, ade8, ade6, and ade7 mutations were
      found to suppress the phenotypic manifestation of the ade2 mutations via
      inactivation of enzymes catalyzing the first, second, third, fourth and fifth
      stages of purine biosynthesis, while the ade1 mutation, which inactivates enzyme
      of the seventh stage, lacks suppressive activity. Strains with single adenine
      mutations, ade4, ade5, ade8, ade6, ade7, or ade1 grow on glycerol- and
      hypoxanthine-containing media. Our data suggest that the new property of the ade2
      mutations could be associated with the accumulation of the AIR-carbole
      ribonucleotide. A mutation resulting in the requirement for serine on the medium
      with glycerol, but not glucose, is described.

PMID- 9589847
TI  - Safety considerations in treating concomitant diseases in patients with asthma.
AB  - The treatment for asthma usually involves a combination of drugs used for
      bronchodilation and to treat underlying airway inflammation. When asthma is
      severe, the regimen used to treat asthma can become quite complicated, often
      using as many as 3 or 4 separate pharmacological agents. As patients with asthma
      get older, their medication regimen can become even more complex with the
      development of numerous other age-related diseases requiring their own list of
      medications. Diseases of the joints, diseases of the eye, cardiovascular disease,
      neurological disease and urological problems represent the most common conditions
      that patients develop, at times needing medications which might interfere with
      asthma management. Many of these diseases require the use of nonsteroidal anti
      inflammatory agents, well known to provoke wheezing in patients with intrinsic
      asthma, and diseases of the eye and cardiovascular system frequently require use
      of beta-blockers which can cause or exacerbate asthma. Managing patients with
      asthma who have other diseases requires constant supervision of their medication
      usage and careful and cautious review of the entire list of medications at each
      presentation.

PMID- 9589851
TI  - [Molecular genetic analysis of DNA structure of pFra plasmids in plague pathogen
      of varying biovar].
AB  - Data on comparative molecular genetic analysis of pFra plasmids from plague
      bacillus belonging to either two biovars (antiqua and orientalis) are presented.
      It was established that during evolution these replicons were rearranged, which
      resulted in the differences between pFra plasmids of plague bacillus of antiqua
      biovar (Yersinia pestis 231 and Y. pestis 358/12) and that of orientalis biovar
      (Y. pestis A1122 and Y. pestis EV). These included inversions of two plasmid DNA
      regions and size differences of 3 kb.

PMID- 9589852
TI  - [Genetic differentiation of Caucasian wood mice: comparison of isozymic,
      chromosomal and molecular divergence].
AB  - Data on the complex genetic analysis of three sympatric species of Caucasian wood
      mice, Apodemus ponticus, A. fulvipectus, and A. uralensis are presented. A high
      degree of genetic differentiation at the isozymic, karyological and molecular
      (nuclear DNA) levels was revealed. The genetic distances between each pair of
      species varied significantly within a wide range depending on the analyzed level
      of the organization of genetic material. Mean values of genetic divergence from
      one species to another were also variable. These findings indicated that
      evolution of chromosomes was slower than that of isozymes, and the degree of
      species divergence was similar on cytogenetic and molecular levels. They also
      suggested that the rates of species evolution could vary in different phyletic
      lineages and on different levels of organization. Some phyletic lineages of
      Apodemus could be distinguished by different directions of evolution.

PMID- 9589853
TI  - [Identification of polygenes in the system achaete-scute in Drosophila
      melanogaster using cluster analysis].
AB  - Data on location of mobile elements mdg1, Dm412, copia, and B104 in 33 isogenic
      lines of Drosophila melanogaster has been processed by means of cluster analysis
      to reveal the relationship between the penetrance for bristle reduction and the
      distribution of mobile elements. The presence of two groups of sites specific for
      lines with contrasting penetrance levels have been demonstrated. The specificity
      suggests that the sites can be associated with the location of corresponding
      polygenes, affecting the penetrance level in mutant lines.

PMID- 9589855
TI  - [Wing shape and developmental temperature in two Drosophila species: different
      wing regions exhibit different reaction norms].
AB  - Reaction norms of different parts of the wing in relation to developmental
      temperature were analyzed in Drosophila melanogaster and D. simulans using
      polynomial adjustments. Six rearing temperatures that encompass the whole
      physiologically possible range of these species were used. Different morphometric
      traits of the wing were shown to have different shapes of reaction norms. In
      particular, traits belonging to the posterior wing compartment and to the edge of
      the wing had various reaction norm shapes, which differed from that of the total
      wing length. Temperatures of maximum values (TMVs) of most traits were higher in
      D. melanogaster than in D. simulans. In general, reaction norm shapes in D.
      simulans were more varied. The results are discussed in relation to thermal
      adaptation of the species studied.

PMID- 9589854
TI  - [A new approach to the analysis of complex chromosomal rearrangements in cell
      hybrids].
AB  - The chromosomal complements of somatic cell pig-mink hybrids was determined by a
      new approach. This approach includes microdissection of metaphase chromosomes,
      generation of chromosome and region-specific DNA libraries, and fluorescence in
      situ hybridization of these libraries with pig lymphocyte chromosomes. The
      studied hybrid cells were shown to contain two small acrocentric chromosomes and
      a microchromosome of porcine origin. Identification of these chromosomes by
      differential GTG-staining was impossible. Chromosome isolation by a
      micromanipulation technique followed by DNA amplification in TOPO-DOP polymerase
      chain reaction provided chromosome-specific DNA libraries of the rearranged
      chromosomes. Based on these libraries, the labeled DNA probes were prepared and
      hybridized to pig chromosomes. This allowed us to determine the origin of the
      material contributing to the hybrid cell chromosomes. One of these chromosomes
      contained five pig chromosomal regions: 15cen-q2; 6q21-q23; 13q21; 13q22; 7q25
      qter, while the other contained the following pig chromosomal regions: 4p12-p13;
      16q12-q14; 12pter-p15. The microchromosome contained the Xp11-Xq11 region. The
      minimal size of the revealed chromosomal regions was about 3 to 4 x 10(6) bp.
      Segregation analysis of the thymidine kinase gene 1 (TK1), which was earlier
      localized to the pig 12p region, and the hybrid cell pig chromosomes in the
      hybrid subclones suggested that TK1 gene can be assigned to 12p15-pter. The
      results obtained demonstrate the efficiency of the applied approach in its
      detailed and reliable description of complex chromosomal rearrangements in hybrid
      clones, when differential chromosome staining failed to identify these
      chromosomes.

PMID- 9589856
TI  - [Genetics of ketosis resistance in cattle].
AB  - The frequency of ketosis among the Black-pied cattle in western Siberia have been
      determined. The genotype of sires and genetic composition of lines were shown to
      affect resistance and susceptibility to ketosis. The heritability of resistance
      to the disease was 0.186. Variation in biochemical parameters and natural
      resistance in cows with ketosis and in healthy cows was studied.

PMID- 9589857
TI  - [Analysis of polymorphism of the angiotensin gene in patients with ischemic heart
      disease and in a random sample from the Moscow population].
AB  - Polymorphism of the (CA)n repetitive sequence in the angiotensinogen gene was
      studied in a random sample of Russian males from the Moscow population and in a
      sample of patients with coronary heart disease. Thirteen allelic variants of this
      microsatellite with 10 to 22 (CA) dinucleotides were revealed. In the patients,
      the spectrum of the allelic variants of the angiotensinogen gene tended to shift
      toward smaller numbers of repeats (n < or = 16). This shift was not associated
      with changes in the lipid composition of blood.

PMID- 9589858
TI  - [Allelic polymorphism and analysis of haplotypes of the muscle protein kinase
      genes and haplotype analysis in residents of northwestern Russia and patients
      with myotonic dystrophy].
AB  - The distribution of alleles with various CTG-repeat numbers was studied and the
      haplotypes for polymorphic sites HhaI and HinfI of mouse muscle protein kinase
      (DMPK) were analyzed in inhabitants of northwestern Russia and in patients with
      myotonic dystrophy (90 and 18 chromosomes, respectively). Twelve normal alleles
      with the triplet-repeat number from 5 to 24 were identified and the alleles with
      five (42.5%) and 11-13 (37%) repeats were found to be predominant. The bimodal
      distribution revealed is similar to those described earlier for other
      populations, however, the frequencies of individual alleles differed from those
      in populations of Europe and Central Russia. No significant differences in
      frequencies of CTG alleles were found in 32 normal chromosomes involved in
      compounds with the mutant chromosomes (i.e., in patients with myotonic dystrophy)
      as compared to their frequencies in the population. However, almost all mutant
      chromosomes (16 of 18) had the same haplotype for intragenic polymorphic sites:
      HhaI-; HinfI+. This haplotype was also inherent in 91% of all chromosomes with
      CTG5 and all chromosomes with a CTG number more than 15. Possible evolution of
      chromosomes with different numbers of triplet repeats mediating their expansion
      and impairing the function are discussed.

PMID- 9589859
TI  - [Genotoxic effects of metabolic derivatives of the new drug phosphabenzide].
AB  - Genotoxic action of four possible metabolites of the new tranquilizer
      phosphabenzide (acetylphosphabenzide, diphenylphosphinylacetic acid,
      phosphabenzide hydrazone with pyruvic acid, bis-1,2
      (diphenylphosphinylacetyl)hydrazine) has been studied. These metabolites belong
      to slightly toxic phosphororganic compounds. The Ames Salmonella/microsomes tests
      performed on strains TA100 and TA98 showed that of these compounds only
      acetylphosphabenzide possessed mutagenic action. Metabolic activation of liver
      microsomes decreased the mutagenic effect. The mechanism of action of
      acetylphosphabenzide is likely to involve the formation of acetylhydrazine,
      capable of producing active electrophiles attacking DNA.

PMID- 9589860
TI  - [Genomic studies of hereditary cardiomyopathies].
AB  - Cardiomyopathies (CMP) clinically and genetically belong to the heterogeneous
      group of myocardial diseases. Among them, three major clinical forms
      (hypertrophic, dilated, and restricted) are distinguished. Genetic factors play a
      substantial role in the etiology of dilated and hypertrophic CMP; family cases
      constitute more than 20% of these forms. Most familial cases of CMP are inherited
      as an autosomal dominant character. Autosomal recessive and X-linked forms are
      rare. Genetic basis for rare familial forms of restricted CMP is unclear. There
      are forms with strict maternal inheritance, which suggests the involvement of the
      mitochondrial genome. The nature of several CMP forms was determined and a number
      of genetic loci for this disease was revealed by modern methods of genetic
      mapping. In familial hypertrophic cardiomyopathy (FHC), four genes have been
      identified (those of beta-myosin heavy chain, alpha-tropomyosin, cardiac troponin
      T, and myosin-binding protein C), all of which encode sarcomeric proteins.
      Maternally inherited forms of FHC are associated with mutations in the
      mitochondrial tRNA genes. Linkage analysis in familial dilated CMP revealed at
      least five genetic loci on chromosomes 1, 3, 9, and X. X-linked forms of dilated
      CMP are caused by mutations in dystrophin gene, but the nature of autosomal forms
      is unclear. A recently recognized form of dilated CMP, arrhythmogenic CMP/right
      ventricular dysplasia (ARVD) is linked to two actinin gene loci on chromosomes 1
      and 14. Genomic studies of CMP provided a basis for a new stage of "genetic
      cardiology", genetic mapping, which at present includes the quest of candidate
      genes for many other human cardiovascular diseases.

PMID- 9589861
TI  - [Trans-mobilization of deletion copies of the mdg3 retrotransposon in cultured
      cells of Drosophila].
AB  - A model system was studied that was associated with the selective amplification
      of shortened copies of the mdg3 retrotransposon in cultured cells of Drosophila
      melanogaster. While full-length mdg3 is present in all species phylogenetically
      closely related to D. melanogaster, the distribution of its deletion copy mdg3del
      was shown to be restricted only to D. melanogaster strains. mdg3del appeared to
      be amplified in two Drosophila cell lines of different origin. A "generalized"
      (statistically averaged) sequence of the shortened copy from a cell line
      Schneider2 was determined. The structure of this copy was shown to be the same as
      in the other tested strains of Drosophila. In addition to the major deletion
      involving the reverse transcriptase domain and a part of the ribonuclease H
      domain, several other deletions, insertions, and point substitutions were also
      revealed in shortened copies. The population of shortened copies was shown to
      result from the amplification of a single mdg3del copy in the genome of
      Schneider2 cells. The results obtained suggest that defective copies of the
      retrotransposon can be trans-mobilized in cultured cells and that the mechanisms
      of retroamplification in cell cultures and in an organism are different.

PMID- 9589862
TI  - [Molecular analysis of a double hyperunstable system y(2ns)sc(me)].
AB  - Molecular analysis of hyperunstable mutations in the adjacent yellow and scute
      loci was performed in a Drosophila melanogaster strain y2ns scme obtained
      earlier. The y2ns scme combination originated from the original y+ns mutation
      associated with the insertion into the regulatory region of the yellow gene of a
      chimeric sequence flanked by deletion copies of the P element. The new
      combination of mutations resulted from an inversion between P-element copies
      located in the adjacent yellow and scute loci. The inversion was flanked by two P
      element copies at one side and one copy at the other side. All three P-element
      copies had various internal deletions and, therefore, could not code for active
      transposase. An introduction of the delta (2-3) gene for transposase induced
      mutagenesis in the y2ns scme strain. Most mutations observed were associated with
      either excision of a single P-element copy or reinversion resulting from the
      recombination between the ends of P elements located in the yellow and scute
      genes. Genetic analysis showed that the alleles resulting from the recombination
      at a high frequency reverted to the original state.

PMID- 9589863
TI  - [Role of the lawc(p1) mutation in the regulation of the white locus expression in
      Drosophila].
AB  - The lawcp1 mutation of the leg-arista-wing complex (lawc) gene alters expression
      of three proneural loci: achaete, scute, and cut. In combination with the product
      of the zeste (z) gene, the product of the lawc gene regulates expression of the
      white (w) gene. The -w B3 mutation was genetically analyzed in compounds with
      various z and w mutations and dominant mutations modifying the z-w interaction.
      The results showed that lawcp1 can enhance the transvection effect. The lawc gene
      was assumed to regulate expression of the white locus at the level of chromatin
      condensation.

PMID- 9589864
TI  - [Ethanol inhibits recombination in somatic cells of gamma-irradiated larvae of
      Drosophila melanogaster].
AB  - Raising of gamma-irradiated larvae of Drosophila melanogaster on an ethanol
      containing medium resulted in decreased mutation frequency in the wing somatic
      mutation and recombination test. This decrease in mutagenicity was mainly caused
      by the reduced recombination frequency. In lines with high activity of cytochrome
      P450, ethanol did not exhibit the radioprotective effect. Frequency of
      spontaneous mutations was significantly different in reciprocal crosses, whereas
      frequency of induced somatic mutations did not depend on the cross direction.
      Addition of 10% ethanol to the medium did not affect spontaneous mutation
      frequency.

PMID- 9589865
TI  - [Polymorphism of the gene of heat shock protein hsp70 in lines of rats with
      normal and hypertensive status].
AB  - RFLP in the hsp70 gene encoding a major heat shock protein was analyzed in rat
      strains with high and normal arterial blood pressure. Dimorphism in the sets of
      DNA fragments was revealed after hybridization of the hsp gene leader sequence
      with rat DNA digested with BamHI restriction endonuclease. Type I RFLP was
      represented by the fragments of 12,200, 6500, 41,000 and 1600 bp in size. Type II
      RFLP corresponded to the set that included the fragments of 12,200, 6500, 2900,
      1600, and 1200 bp in size. Interstrain polymorphism was demonstrated for the
      fragments of 4100, 2900 and 1200 bp. Furthermore, analysis of different rat
      strains showed that the 2900- and 1200-bp fragments were linked and formed by
      cleavage of the 4100-bp fragment with restriction endonuclease. This polymorphism
      was probably caused by the point A-->T mutation occurring in the BamHI
      recognition site located in the leader sequence of the hsp70 gene at a distance
      of +35 bp from the coding sequence. Examination of interstrain RFLP in the hsp70
      gene indicated that the presence of 2900-bp fragment was not associated with
      hypertensive status in all experimental models of inherited arterial
      hypertension. This confirms the assumption on genetic heterogeneity of this
      common disease.

PMID- 9589866
TI  - [Chromosomal localization of nine genes in common shrew (Sorex araneus)].
AB  - Syntheny and localization of the following genes in common shrew Sorex araneus
      were determined: isocitrate dehydrogenase 2 (IDH2), acid phosphatase 2 (ACP2),
      glutamine--pyruvate--oxo-acid transaminase (GPT), and inorganic pyrophosphatase
      (PP) on chromosome ik; adenylate kinases 1 and 3 (AK1 and AK3) on chromosome af;
      and enolase 1 (ENO1) on chromosome jl. Two genes were assigned to definite arms:
      aminoacylase 1 (ACY1) to arm p of chromosome mp and glutamic-oxaloacetic
      transaminase 1 (GOT1) to arm q of chromosome qr. Thus, 26 genes marking eight out
      of ten chromosomes are present now on the cytogenetic map of common shrew. These
      include previously described localizations.

PMID- 9589867
TI  - [Polymorphism in region V of mitochondrial DNA in indigenous populations of
      northern Asia].
AB  - The insertion and deletion polymorphisms of region V of mitochondrial DNA (mtDNA)
      were studied in three indigenous populations of northern Asia: Yakuts, Evens, and
      Koryaks. In Evens and Koryaks, polymorphism was not found. In Yakuts, a 9-bp
      deletion and a 4-bp insertion were revealed in mtDNA region V. Sequencing of
      mtDNA region V confirmed the presence of these mutations. The results obtained,
      together with data published earlier, indicate that the frequencies of both the
      deletion and the insertion in Yakuts are 1.21%. The association between the 9-bp
      deletion and the types of the mtDNA control region were studied. The data
      obtained indicated that this deletion belonged to the Asian deletion cluster.

PMID- 9589868
TI  - [Polymorphism of mitochondrial DNA in Northern Selkups].
AB  - The RFLPs detected by the AvaII, BamHI, EcoRV, KpnI, HaeIII, and RsaI restriction
      enzymes in the D-loop region of mitochondrial DNA of the Northern Selkups were
      analyzed. Frequencies of the rare variants were estimated for all polymorphic
      sites examined. A total of 16 mitotypes were described. Results were compared
      with the literature data on mitochondrial DNA polymorphism in Caucasoid and
      Mongoloid populations. High frequency of the KpnI bp 16129 site loss (28.14%)
      together with a remarkably reduced number of mitotypes in the group of variants
      with the frequency of 2% compared to the Russians and Mongols, was considered to
      be the most informative population feature of the Northern Selkups. All variants
      found in the Selkups, occurred more frequently in the Mongols than in Russians.
      Four out of ten rare variants (frequency < 2%) observed in the Selkups were
      detected in Mongols and Russians. The frequency of three of these variants was
      higher in the Russian population. Six mitotypes were characterized as Selkup
      specific. These observations suggest a considerable reduction of mitochondrial
      gene pool diversity in Northern Selkups compared to larger ethnic groups of
      Mongoloids and Caucasoids. The structure of mitochondrial genome in Selkups is
      defined by the presence of the major Mongoloid and minor Caucasoid components,
      which suggests complex ethnogeny of the contemporary Selkup population.

PMID- 9589869
TI  - [Genetic-demographic processes in the Moscow population in the mid 1990's.
      Analysis of ethnogeographic migration parameters (isolation by distance)].
AB  - Geographic parameters of migration were analyzed on the basis of data on
      birthplaces of individuals who contracted marriages in Moscow 1955, 1980, and
      1994 to 1995. It was shown that the relationship between the migration rate and
      distance significantly changed in the 1990s. Investigation of ethnic composition
      of migrants demonstrated that an increase of migration activity of residents of
      Transcaucasia and North Caucasus recorded in 1990s was associated with an
      increase in migration to Moscow of representatives of indigenous populations of
      these regions rather than with repatriation of Russians. Analysis of migration
      with the use of the Malecot's model of isolation by distance showed that
      genetically effective migration accounted for 1/7, 1/3, and 1/4 of the total
      marital migration rate in 1995, 1980, and 1990, respectively. An increase in mean
      migration distance in 1995 to 1980 is explained mainly by a decrease in the
      proportion of short-range migration. The level of isolation by distance was
      extremely low and showed a trend to further decrease during the 40-year time
      interval. Parameters of the model indicated that at present the population of the
      central part of the Moscow oblast in the 80-km zone from the city center should
      be assigned to the Moscow population.

PMID- 9589870
TI  - [Construction and characteristics of a cosmid library of genes of the bacterium
      Cornyebacterium glutamicum ATSS13032].
AB  - A representative genomic library of the Corynebacterium glutamicum ATCC 13032
      genes in a cosmid vector Lorist6 was created. The cosmids contain inserts of
      bacterial DNA obtained by partial digestion with the Sau3A I restrictase. Five
      hundred and thirty individual primary recombinant clones were transferred into
      the wells of microtiter plates, where they are now being preserved. The average
      size of the bacterial DNA inserts determined via a sum of restriction fragment
      sizes of recombinant molecules is about 38 kb. The capacity of the obtained gene
      library is 8.4 equivalents of the C. glutamicum genome, i.e., every fragment of
      the genome is on average represented by eight clones and is presented in at least
      one clone with the probability > 99%. Clone grids (sets of recombinant clones
      located on the hybridization membrane in regular and reproducible order) were
      created. Specificity of the created clone library and its representativeness were
      confirmed experimentally by hybridization of clone grids with DNA probes
      corresponding to unique regions of the Corynebacterium genome. A plasmid
      containing the pheA prephenate dehydratase gene, olygonucleotide corresponding to
      the lysC gene, and the 21 RNA probe obtained from the insert ends in different
      cosmids were used as probes. The created set of clones allows the construction of
      a cosmid contig overlapping the C. glutamicum genome and a physical genetic map
      on its base.

PMID- 9589871
TI  - [Correlation between the number of sites, transcript levels and transposition
      frequency of retrotransposon copia in Drosophila melanogaster].
AB  - Numbers of copia transcripts in testes of files from five Drosophila melanogaster
      lines were compared by means of Northern blot hybridization. Four of these lines
      were closely related differing only by transposition rates and the number of
      copia sites in the genome. The fifth line, which was not related to the others,
      was characterized by lack of transpositions and the lowest copia copy number.
      Positive correlation between total copia transcript level and its copy number and
      transposition rate was observed. Therefore, transcription rate of copia
      retrotransposon in tests is largely controlled by the level of its transcription,
      which, in turn, is regulated by the number of retrotransposon copies in the
      genome. These data contradict the hypothesis on self-regulation of
      retrotransposon copy number in the genome.

PMID- 9589872
TI  - [Cloning of the gene leg-arista-wing complex and analysis of its mutant
      derivatives in Drosophila].
AB  - Insertion of a double copy of P element was shown to be the cause of the lawcp1
      mutation. Mapping and cloning of a DNA fragment bearing the lawc locus was
      carried out. New alleles of this gene were characterized.

PMID- 9589873
TI  - [Study on urinary levels of interleukin-1 beta, interleukin-6 and tumor necrosis
      factor-alpha in patients with renal cell carcinoma].
AB  - We examined the preoperative and postoperative, urinary levels of the cytokines,
      interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor
      alpha (TNF-alpha) in 14 patients with renal cell carcinoma (RCC), and 9 patients
      who underwent nephrectomy as donors (controls). Although urinary IL-1 beta was
      measurable in every subject, both IL-6 and TNF-alpha were undetectable in 12 of
      the 14 patients. None of the urinary cytokines showed levels significantly
      different from the controls preoperatively. Urinary levels of IL-1 beta showed no
      correlation with clinical stage or histological grade. Only urinary IL-1 beta was
      significantly elevated after nephrectomy, when compared with the controls (P <
      0.05). However, urinary IL-1 beta showed no correlation with operative blood loss
      or postoperative infection. These findings suggest that measurement of urinary
      cytokines is not useful for diagnosis or monitoring of therapy in RCC patients.

PMID- 9589874
TI  - [Long-term survival of bladder preservation therapy with radiation and
      chemotherapy for locally invasive bladder cancer].
AB  - The prognoses and prognostic factors of the 54 patients with locally invasive
      bladder cancer who underwent bladder preservation therapy at Yokohama City
      University Hospital between 1977 and 1995 were analyzed statistically. The
      therapeutic modalities of bladder preservation were mainly radiation or
      chemotherapy. The prognosis for the patients who underwent bladder preservation
      therapy was worse than that for the patients who underwent total cystectomy. The
      prognostic factors of these patients were size and grade of tumor, presence of
      hydronephrosis and performance status (PS) of the patients by univariate
      analysis. Tumor grade was the most predictable prognostic factor using
      multivariate analysis. Only 17 patients survived more than 5 years after
      treatment; 78% of the survivors had good PS (0 or 1). Five of them died of cancer
      and two patients were alive with cancer. All of them had G3 tumors. These results
      suggest that patients with locally invasive G2 tumor could be candidates for
      bladder preservation therapy and patients who underwent bladder preservation
      therapy should be evaluated at 10 years post-therapy.

PMID- 9589875
TI  - [Prostate cancer screening using prostate specific antigen (PSA) in Tokatsu
      Hospital--examination of lost-to-followup cases].
AB  - We studied the usefulness of prostate cancer screening using prostate specific
      antigen (PSA) and PSA density (PSAD). In the first year of this screening (1995),
      we detected prostate cancer in 11 out of 550 (1.7%) subjects. Only 33 of the 47
      (70%) subjects whose PSA values were greater than the cut-off value could be
      followed the following year. The remaining 14 subjects could not be followed
      mainly because of absence of urination difficulty at that time. The international
      prostate symptom score (I-PSS) sum and the quality of life (QOL) score at the
      screening in the unfollowed group were significantly lower than those in the
      followed group. The subjects who must be followed and whose QOL score and I-PSS
      sum are low at the time of screening need more careful and persuasive explanation
      from the urologist on the importance of long-term follow-up.

PMID- 9589876
TI  - [Spontaneous rupture of malignant fibrous histiocytoma arising from the renal
      capsule: a case report].
AB  - We report a case of spontaneous rupture of malignant fibrous histiocytoma. A 50
      year-old male with right flank pain was referred to our hospital. Computed
      tomography (CT) showed a heterogeneous space-occupying lesion on the upper pole
      of the right kidney. Selective right renal arteriography revealed a hypovascular
      mass. Preoperative clinical diagnosis was spontaneous rupture of renal cell
      carcinoma. Radical nephrectomy was performed. Histopathological diagnosis was
      malignant fibrous histiocytoma arising from the renal capsule.

PMID- 9589877
TI  - [Retroperitoneal Castleman's disease: a case report].
AB  - We report a case of retroperitoneal Castleman's disease. A 57-year-old woman was
      referred for evaluation of microscopic hematuria. Computed tomography
      demonstrated a small solid retroperitoneal mass. The mass was surgically resected
      and the histopathological diagnosis of the resected tissue was hyalin vascular
      type of Castleman's disease. Although retroperitoneal Castleman's disease is an
      uncommon disease. We should always consider this tumor in the differential
      diagnosis of retroperitoneal tumors.

PMID- 9589878
TI  - [Adrenal pheochromocytoma associated with renal cell carcinoma: report of two
      cases].
AB  - Two cases of adrenal pheochromocytoma associated with renal cell carcinoma are
      reported. The first case was in a 56-year-old woman who had been treated for
      hypertension. Computerized tomography (CT) scan revealed a right renal tumor and
      a right adrenal mass. Endocrinological examination and 131I-MIBG scintigraphy
      confirmed the diagnosis of pheochromocytoma. Right radical nephrectomy was
      performed under stable blood pressure. The second case was in a 45-year-old man
      who had been treated for gastric ulcers. CT scan incidentally revealed a right
      renal tumor and a left adrenal mass. He was normotensive and endocrinologically
      normal. Right radical nephrectomy and left adrenalectomy were performed, followed
      by corticosteroid supplementation. In both cases, histopathological diagnosis was
      renal cell carcinoma and adrenal pheochromocytoma. Both patients had no clinical
      evidence for von Hippel-Lindau disease such as tumorous lesions of the central
      nervous system, spinal cord and retina, and cystic lesions of the kidney and
      pancreas.

PMID- 9589879
TI  - [Pulmonary metastasis from renal cell carcinoma diagnosed by using thoracoscopic
      biopsy: a case report].
AB  - A 70-year-old woman underwent radical nephrectomy for right renal cell carcinoma
      and received prophylactic interferon-alpha (rHuIFN-alpha) administration for one
      year. Followup computerized tomography scan showed a small nodule in the right
      lung 39 months postoperatively. Pulmonary nodules had become multiple and
      increased in size (6 mm) at 53 months. To examine the pulmonary lesions,
      histopathologically thoracoscopic biopsy of the right pulmonary nodule was
      performed and the diagnosis of metastatic renal cell carcinoma was confirmed.
      Because of its minimal invasiveness, thoracoscopic biopsy may be indicated in
      selected cases.

PMID- 9589880
TI  - [A case of laparoscopic nephrectomy for ectopic vaginal ureter in a child].
AB  - An 11-year-old girl presented with continuous incontinence since infancy. Neither
      intravenous pyelography nor renal scintigraphy demonstrated the left upper
      urinary tract, but a very small left kidney was detected close to the 3rd lumbar
      vertebrae on computed tomography (CT). After cystoscopy, the patient was
      diagnosed with ectopic vaginal ureter and hypoplastic kidney. Laparoscopic
      nephrectomy was performed. Before surgery, a ureteral occlusion catheter was
      inserted through the meatus which opened in the vagina. The catheter was very
      useful for locating the small kidney during surgery. The procedure was successful
      and the surgical duration was short (123 min.) with only slight hemorrhage (15
      ml). The patient was able to attend school on the seventh postoperative day. We
      recommend laparoscopic surgery for the treatment of ectopic ureter.

PMID- 9589881
TI  - [A collision tumor between squamous cell carcinoma and malignant lymphoma of
      urinary bladder: a case report].
AB  - A 68-year-old-male was admitted to our hospital with the chief complaint of
      macrohematuria. He was diagnosed with malignant lymphoma at 63 years old.
      Cystoscopy and computerized tomography revealed a non-papillary and broad based
      tumor at the anterior wall of the urinary bladder and partial cystectomy was
      done. Pathological diagnosis was collision tumor between squamous cell carcinoma
      and malignant lymphoma. To our knowledge, this is the 13th case of collision
      tumor associated with genitourinary organs in the literature.

PMID- 9589882
TI  - [Migration of surgical sponge retained at transvaginal hysterectomy into the
      bladder: a case report].
AB  - Urge incontinence and frequency, persisting despite oral anticholinergics and
      antibiotics for four months, brought a 72-year-old woman to our hospital. Plain
      abdominal X-ray followed by cystoscopy demonstrated a large stone (43 x 37 mm) in
      the bladder, and the patient underwent suprapubic cystotomy to remove the stone.
      The stone contained a surgical sponge, which was apparently left in situ at
      transvaginal hysterectomy two years previously. The sponge had most likely eroded
      the bladder wall and migrated into the cavity. We found a total of 17 cases
      reported in Japan of a surgical sponge migrating into the bladder. In particular,
      our case was associated with transvaginal surgery, while the other 16 cases
      involved transabdominal surgery.

PMID- 9589883
TI  - [Prostate cancer with high serum level of CEA and CA19-9: a case report].
AB  - We report a case of primary adenocarcinoma of the prostate cancer producing
      carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). An 80-year
      old man admitted to our hospital with the complaint of appetite loss. Serum CEA
      and CA19-9 levels were increased to 28.9 ng/ml (normal < 3.5) and 271 U/ml
      (normal < 37), respectively. Serum PSA level was also high (33 ng/ml; normal <
      3.6). Computed tomography (CT) demonstrated para-aortic lymph node swelling and
      bone scan revealed multiple bone metastasis. Prostate biopsy was performed and
      the specimen showed no evidence of malignancy. However endocrine therapy was
      started because of the strong suspicion of prostate cancer. In spite of the
      treatment, the patient died 2 months after the treatment. Histology of autopsy
      specimen demonstrated primary prostate cancer (poorly differentiated
      adenocarcinoma) and metastases to multiple organs, such as lungs, liver, thyroid,
      bone marrow and adrenals. Immunohistochemical staining for CEA, CA19-9 and PSA
      demonstrated the existence of each protein at both primary and metastatic sites.

PMID- 9589884
TI  - [A case of septic shock following incarceration of the penis].
AB  - An 84-year-old male presented to the emergency room with the chief complaint of
      painful, swollen penis following the use of a constriction ring to maintain
      penile erection. A high fever, chills and hypotension were recognized. Septic
      shock was presumed, and administration of antibiotics was started. Microbiologic
      cultures revealed Escherichia coli in blood. We herein report a rare but serious
      complication accompanying incarceration of the penis.

PMID- 9589885
TI  - [A case of malignant lymphoma presenting as epididymal tumor].
AB  - A 56-year-old man visited our hospital with the complaint of painless swelling of
      right scrotal contents. Right orchiectomy was performed. Histopathological
      diagnosis was malignant lymphoma of the epididymis, without involvement of the
      testis. Bone marrow biopsy and Ga scintigram showed a normal pattern, while a
      swollen retroperitoneal lymph node (3 cm) was found by computed tomography (CT).
      The CT also showed a small mass lesion in the left upper lung field. After 2
      courses of chemotherapy for malignant lymphoma, left upper lobectomy was
      performed at another clinic. Pathological diagnosis of the surgical specimen was
      moderately differentiated adenocarcinoma. The patient died without known causes,
      8 months after the orchiectomy.

PMID- 9589886
TI  - [Clinical effect of propiverine hydrochloride on urinary incontinence].
AB  - Propiverine hydrochloride was given to patients with subjective symptoms of
      urinary incontinence and its effect was evaluated in relation to the pathogenesis
      of incontinence. High improvement rates were obtained in patients with stress
      incontinence as well as those with urge incontinence. There was no significant
      difference between the two patient groups in the degree of improvement of
      subjective symptoms or objective findings. Under the present circumstances, where
      urinary incontinence is often treated by medical doctors other than urologists,
      this drug may be useful for the treatment of urinary incontinence since it would
      produce high therapeutic effects irrespective of the pathogenesis of
      incontinence.

PMID- 9589888
TI  - Lectin-staining pattern in extratesticular rete testis and ductuli efferentes of
      prepubertal and adult horses.
AB  - This study was undertaken to determine the lectin affinity of the extratesticular
      rete testis and ductuli efferentes epithelial cells in adult and prepubertal
      horses, using ten different lectin horseradish peroxidase conjugates: Con-A, LCA,
      WGA, GSA-II, SBA, PNA, RCA-I, DBA, UEA-I, and LTA. In some cases, treatments with
      sialidase and KOH preceded the lectin staining. In sexually mature and immature
      horses the results showed the presence of different kinds of sialoglycoconjugates
      with the terminal sialic acid linked to D-GalNAc and beta-D-Gal residues in the
      rete testis. In the apical surface and cytoplasm of epithelial cells lining the
      ductuli efferentes of the adult horse, glycoconjugates with alpha-D-Man and/or
      alpha-D-Glc, GlcNAc, D-GalNac and beta-D-Gal residues were evidenced, whereas in
      the prepubertal horse only the apical surface of the ductuli efferentes
      epithelial cells resulted reactive toward some lectins. The differences observed
      in the presence of glycoconjugates between adult and prepubertal horse ductuli
      efferentes, suggest a hormonal control of the function of these tracts of the
      post-testicular ducts.

PMID- 9589887
TI  - The effects of chronic administration of captopril on the mouse median eminence.
AB  - The effects of Captopril (an angiotensin-converting enzyme inhibitor) on the
      median eminence (ME) of the male albino mouse have been examined using
      morphometric and immunohistochemical procedures. We measured the nuclear area of
      the ependymocytes of the ME and of the glial cells of the reticular external zone
      of the ME. We also determined the cell/neuropil coefficient (CNC), which
      expresses the relation between cellular area and neuropil of the ME, and the
      global volume of the ME in each animal. For the immunohistochemical study we used
      rabbit antiarginine-vasopressin, and compared the results in the different groups
      of mice. We detected an increased in the immunoreactive material (arginine
      vasopressin, A-V) and an increase in the global volume of the organ and also an
      increase of the neuropil of the ME after the longest exposure to the drug. These
      alterations could be related to the inhibition of the brain angiotensin II by
      captopril and the accumulation of vasopressin in the fibrous tract that runs from
      the paraventricular nucleus (PVN) to the neurohypophysis.

PMID- 9589889
TI  - Morphometry of the human splenic artery: muscular columns, morphofunctional
      aspects and developmental implications.
AB  - There is a paucity of studies in the literature concerning the structural
      characteristics of the arterial wall in the abdominal region using human material
      and specialized morphometric techniques. In the present study we carry out the
      morphometric study, describing a series of structural peculiarities in 12
      segments of the human splenic artery. Among these the presence of length-wise or
      spiral-shaped muscular columns in the medial layer which mark and reduce the
      diameter of the arterial lumen is of major importance. In its underlying intima
      small localized thickenings appear which, with age may become generalized. We
      also analyze the different intimal thickenings and such indices as the Intimal
      Thickening Index, Lumen Reduction Index and Pathologic Thickening Index, with
      differences among the groups we have considered. The study of elastin in the
      various parietal structures help us to understand the possible pathogenesis of
      the thickenings, and to clarify the important morphological-functional
      correlation for the regulation of blood flow which exists in this arterial
      region.

PMID- 9589890
TI  - The deep-sea teleost cornea: a comparative study of gadiform fishes.
AB  - The corneal structure of three deep-sea species of teleosts (Gadiformes,
      Teleostei) from different depths (250-4000 m) and photic zones are examined at
      the level of the light and electron microscopes. Each species shows a similar but
      complex arrangement of layers with a cornea split into dermal and scleral
      components. The dermal cornea comprises an epithelium overlying a basement
      membrane and a dermal stroma with sutures and occasional keratocytes. Nezumia
      aequalis is the only species to possess a Bowman's layer, although it is not well
      developed. The scleral cornea is separated from the dermal cornea by a mucoid
      layer and, in contrast to shallow-water species, is divided into three main
      layers; an anterior scleral stroma, a middle or iridescent layer and a posterior
      scleral stroma. The iridescent layer of collagen and intercalated cells or
      cellular processes is bounded by a layer of cells and the posterior scleral
      stroma overlies a Descemet's membrane and an endothelium. In the relatively
      shallow-water Microgadus proximus, the keratocytes of the dermal stroma, the
      cells of the iridescent layer and the endothelial cells all contain aligned
      endoplasmic reticulum, which may elicit an iridescent reflex. No alignment of the
      endoplasmic reticulum was found in N. aequalis or Coryphanoides (Nematonurus)
      armatus. The relative differences between shallow-water and deep-sea corneas are
      discussed in relation to the constraints of light, depth and temperature.

PMID- 9589891
TI  - Morphological studies of glomeruli in obstructive kidneys by confocal laser
      scanning microscopy and quick-freezing replica method.
AB  - Morphological changes of glomeruli in obstructive kidneys were studied by using
      confocal laser scanning microscopy (CLSM), and quick-freezing and deep-etching
      (QF-DE) method. Twenty-one rabbits were divided into three groups, consisting of
      control, 6-hr bilateral ureteral obstruction (BUO) and 24-hr BUO. In the
      experimental groups, the attenuation of cell bodies, the lengthening and
      stretching of major processes, the cystic formation in the cytoplasm and the
      fusion of foot processes were observed on conventional ultrathin sections. These
      changes in the 24-hr BUO group were more clearly observed than those in the 6-hr
      BUO group. By the CLSM, cell bodies and foot processes of podocytes in the
      experimental groups were more intensely immunostained with anti-alpha-tubulin
      antibody and phalloidin-FITC. By the QF-DE method, cytoskeletons in the podocyte
      cell bodies and major processes were composed of numerous intermediate filaments,
      but distinct changes of actin filaments and microtubules were not observed in the
      control and experimental groups. Considering the physiological changes in BUO,
      the mechanical stress appeared to be brought about by hemodynamic factors rather
      than the change of intratubular pressure, resembling the morphological changes in
      experimental animals with hyperfiltration and the homeostatic adaptation of
      podocytes under the BUO condition.

PMID- 9589892
TI  - An electron microscopic study of Helicobacter pylori in the surface mucous gel
      layer.
AB  - This study describes the distribution of spiral and coccoid forms of Helicobacter
      (H.) pylori within the surface mucous gel layer (SMGL) on human gastric mucosae.
      Gastric mucosae infected with H. pylori were obtained from surgically removed
      stomachs of 14 cases of gastric cancer. The glycocalyx of the spiral and coccoid
      forms of H. pylori was examined for specific lectin labeling. Coccoid forms were
      identified in 11 of these cases (78.6%). The SMGL, which was from 50 to 100
      microns in thickness, contained H. pylori throughout its entire thickness.
      Variously-sized vacuole-like clear areas were present near H. pylori. The
      glycocalyx on both the spiral and coccoid forms was similar in its staining with
      the 8 types of lectins tested. However, the staining pattern of the lectins
      varied among different samples. The numerous fibrillae-like filaments radiated
      from the surface of the bacteria and appeared to link the bacteria to the surface
      mucous cells or the surrounding mucus. These fibrillae-like filaments were not
      specifically stained by the lectin reactions, suggesting absence of sugar
      molecules.

PMID- 9589893
TI  - Gut glycoconjugates in Sparus aurata L. (Pisces, Teleostei). A comparative
      histochemical study in larval and adult ages.
AB  - This study examined the gut of the euryaline fish Sparus aurata, from the pharynx
      to the rectum. The specimens were collected from adult animals, both sexes, and
      several larval and juvenile stages, from 4 to 135 days of age. Histochemical
      methods of distinguish neutral and acidic glycoconjugates, as well as specific
      techniques to identify acidic glycoconjugates which contained O-acylated sialic
      acids were used. The presence and distribution of sugar residues in the
      oligosaccharide side chain of glycoconjugates were investigated with the use of
      biotinylated lectins. The pharynx and oesophagus of adult fishes showed the
      presence of abundant secretory cells which synthesized a large quantity of
      neutral, as well as sulphated and sialylated glycoconjugates, with different
      cellular combinations of them in the proximal and distal tract. This may be
      related to the complex functions carried out by this end of the gut in a marine
      euryaline fish. Epithelial secretory cells were found in the developing
      oesophagus during larval life (14 days) earlier than in the stomach and intestine
      (34 days). The simple columnar epithelium that lined the gastric mucosa of adult
      fish synthesized a mixture of neutral and acidic glycoconjugates, whereas during
      larval life it was shown to contain neutral glycoconjugates only. The intestinal
      goblet cells were shown to secrete both neutral and acidic glycoconjugates,
      especially sulphated forms. The adherent mucus gel of the gastric and intestinal
      mucosa contained many sugar residues, as revealed by lectin histochemistry. This
      work clearly demonstrates that the quality of gut mucosubstances varies in
      different ages and in regions of the fish alimentary canal. This is possibly
      caused by changes in environmental conditions and may in turn sustain functional
      alterations of the digestive apparatus.

PMID- 9589894
TI  - Distribution of VIP receptors in the human submandibular gland: an
      immunohistochemical study.
AB  - Distribution of vasoactive intestinal polypeptide (VIP)-immunoreactive nerve
      fibers and VIP-receptor (VIP-R)-immunoreactive sites in the human submandibular
      gland were examined by the peroxidase-antiperoxidase method using the specimens
      taken from patients that had not received radiotherapy. VIP-immunoreactive fibers
      were found around both serous and mucous acini, the duct system, and those around
      the mucous acini were more numerous than those around the serous acini. VIP-R
      immunoreactivity was restricted to the mucous acini and the intercalated duct
      segment. The serous acini, striated duct, and excretory ducts lacked VIP-R
      immunoreactivity. These findings suggest that the mucous acinar cells contain VIP
      R, and that VIP-R-mediated VIP action is involved in regulating synthesis of
      viscous saliva and its release.

PMID- 9589895
TI  - Induction of DNA fragmentation by total-body irradiation in murine liver.
AB  - Total-body irradiation (TBI) is an accepted modality to treat patients with
      disseminated tumors. The influence of the treatment on normal tissues is
      evaluated using mice by measuring the rate of the induction and distribution of
      apoptosis, as well as DNA fragmentation which occurs in the murine liver within
      hours of irradiation. Unanesthetized female C3H/He mice were exposed to gamma-ray
      TBI of 2, 7, and 20 gray (Gy) delivered from 60Co at a dose rate of 114 cGy/min.
      Frozen sections of livers which were excised from the animals at various times
      after irradiation were stained by hematoxylin-eosin (H-E) to count numbers of
      apoptotic cells, or were examined to detect DNA fragmentation. The percentages of
      apoptotic cells and length of the period during which the maximum levels of the
      percentages were exhibited showed a dose-dependent increase in the sections
      stained with H-E. No positive cells for 3'-OH ends of fragmented DNA were found
      in the liver before TBI, whereas positive cells were observed immediately after
      irradiation without dose-dependency, these positive cells returned to nearly
      basal levels after several hours. Positive cells were observed prior to showing
      apoptosis, suggesting that DNA fragmentation occurs immediately after TBI
      independent of apoptosis. The difference in the time courses between induction of
      DNA fragmentation and of apoptosis was not observed in other organs or in the
      samples treated with the detergent. These results suggested that the 3'-OH ends
      newly generated by TBI were masked by a detergent-soluble DNA-binding molecule
      which might be preferentially present in the murine liver.

PMID- 9589896
TI  - Low-intensity ultrasound energy applied to the testes of aged rats.
AB  - Previous studies from our laboratory have shown that low-intensity ultrasound
      applied to the scrotum of prepubertal rats causes a 62% increase in plasma
      testosterone, suggesting a possible stimulation of LH receptors and/or the
      enzymes controlling the steroidogenic process. The purpose of the present study
      was to investigate whether low-intensity ultrasound has a stimulatory effect on
      the androgenic activity of aged testes. In addition to plasma testosterone, LH
      and FSH, the testicular spermatogenic status was also analysed. Ultrasound
      applied to the scrotum of aged rats did not stimulate sperm production, which was
      significantly reduced compared to sexually mature animals, and failed to re
      establish the steroidogenic testicular function, which was decreased by 74%,
      suggesting an inherent loss of gonadal steroidogenic competence.

PMID- 9589897
TI  - The torus longitudinalis in the gilthead seabream: an undescribed fiber tract
      link with the valvula cerebelli.
AB  - In this paper, we present a brief anatomical description of the torus
      longitudinalis and the valvula cerebelli in a percomorph fish, the gilthead
      seabream (Sparus aurata) based on the analysis of serial brain sections stained
      by paraldehyde fuchsin, Groat's hematoxylin-picroindigocarmin and cresyl violet.
      The existence of a small undescribed fiber tract directly bridging the ventral
      torus longitudinalis and the granular layer of the rostral valvula cerebelli is
      also reported. This small fiber tract was observed in its integrity on a few
      transverse sections providing that the angle of sectioning was appropriate. The
      existence of the anatomical link between the TL and the VC described in this
      paper might sustain the role of the TL as part of an ascending cerebello-tectal
      circuit, at least in gilthead seabream. However, these fibers might also
      represent fibers of passage originating from other brain structures.

PMID- 9589898
TI  - Quantitative assessment of normal and potentially premalignant epithelium at
      different levels of human colorectal crypts.
AB  - The present study uses morphometric techniques to assess whether altered
      differentiation patterns exist in PPM which might reflect its premalignant
      status. Samples were obtained from resected malignant lesions of large bowels of
      10 Chinese patients. Normal (N) samples were biopsied from the margins of each
      resected large bowel. Potentially premalignant (PPM) mucosae were obtained from
      within 2 cm of the margins of the malignant lesions. Tissues were processed for
      histological examination and using strict criteria, colorectal crypts were
      divided into basal (B), intermediate (I) and surface (S) segments. Interactive
      digitisation of sections from each group was used to generate the following
      morphometric parameters in each segment: nuclear profile circularity indices (NSF
      and NCI); nuclear numerical density (NA and NV); the degree of deviation of the
      major nuclear axis in relation to the epithelial-connective junction (AGDMAX);
      cell height (CH); the distance between nuclear apex to cell apex (DNACA); the
      distance between cell base to nuclear apex (DCBNA); stratification index (SI)-
      the ratio of DCBNA and CH; and the volume density of mucous vacuoles in the
      reference epithelium (VVMV,EP). In comparisons of different segments within
      groups, the nuclei at the S segment of N and PPM crypts were more irregular and
      less circular in shape than nuclei from other segments. There was a shift of
      nuclear profile shape (NSF and NCI) from circular to ellipsiodal between B and S
      segments. In comparisons of similar segments between groups, no significant
      nuclear shape changes were detected in nuclei of PPM crypts when compared with
      nuclei in similar segments of N crypts and the pattern of nuclear shape
      alterations resembled those of normal crypts. In comparisons of different
      segments within groups of N and PPM crypts, AGDMAX, DNACA, DCBNA, CH and SI
      parameters demonstrated that epithelial cells at the I segments have more
      centrally positioned nuclei with the tallest epithelial height when compared with
      epithelial cells in other segments of both crypts. In B segments, nuclear NA and
      NV were almost double those of other segments in both N and PPM crypts, with
      marked reductions in these parameters between B and I segments. VVMV,EP was
      significantly highest in the I segment and significantly lowest in the S segment
      of both groups. Both N and PPM crypts showed similar trends in VVMV,EP within the
      crypt segments but when comparing similar segments between both crypts, a
      significant difference was detected only between S segments. The alterations of
      nuclear shape and packing densities, orientation and mucous content in N crypts
      were similarly expressed in PPM crypts and distinct differences in numerical
      density (NV) and stratification index existed in crypts between these two groups
      when comparing similar segments. All values in PPM were consistently lower when
      compared with N crypts. These preliminary observations may represent a subtly
      altered state of cellular differentiation in PPM which may be a reflection of
      early preneoplastic transformation.

PMID- 9589899
TI  - Morphological heterogeneity of myeloperoxidase-positive granules in normal
      circulating neutrophils: an ultrastructural study by cryosection.
AB  - Ultrastructural localization of myeloperoxidase (MPO) in the granules of human
      circulating neutrophils was examined by cryosection. On careful comparison with
      the morphological characteristics of the granules by conventional transmission
      electron microscopic study, large MPO-positive granules were divided into five
      types by immunocryoultramicrotomy using monoclonal antibody. Double staining of
      MPO and lactoferrin (or lysozyme) was also performed. Lactoferrin was generally
      detected in MPO-negative granules. Lysozyme immunostaining was present in MPO
      positive and -negative granules. These data may suggest different functions among
      large MPO-positive granules of human circulating neutrophils.

PMID- 9589900
TI  - Synaptophysin immunoreactivity in the cat cochlear nuclei.
AB  - The presence of synaptophysin, a presynaptic Ca2+ binding glycoprotein, has been
      analyzed in the cochlear nucleus complex of the adult cat using an
      antisynaptophysin monoclonal antibody. Synaptophysin immunoreactivity was
      differently distributed between regions of cochlear nuclei. Terminal boutons
      contacting directly with neurons (cell bodies and dendrites) or in the neuropil
      of ventral and dorsal cochlear nuclei appeared immunostained. In the ventral
      cochlear nucleus, synaptophysin-labelled boutons were clearly defined in contact
      with spherical, globular, multipolar, octopus and cochlear-nerve root neurons.
      However, the dorsal cochlear nucleus showed a dense immunostained network of
      synaptophysin-labelled puncta, inside which some neuron cell bodies were
      observed. The present findings show a differential distribution of synaptophysin
      immunostained boutons between the ventral and the dorsal cochlear nuclei of the
      cat. The present description of the different synaptophysin-labelled terminal
      boutons in the cochlear nuclei complex and their pattern of distribution, will be
      useful for further studies on development, degeneration or regeneration of the
      peripheral auditory pathway.

PMID- 9589901
TI  - Genomic imprinting and carcinogenesis.
AB  - The Mendelian inheritance is based on the fundamental rule in which mammalian
      genes are expressed equally from two homologous biparental alleles. Recently a
      small number of genes have been identified to show an exception to this rule in
      that homologous alleles can function differently in somatic cells depending on
      whether they come from the mother or the father. This intriguing biological
      phenomenon is called as genomic imprinting which does not conform classical
      Mendelian inheritance and has potentially far reaching implications for genetics,
      evolution, developmental biology and pathology including cancer. The gene
      encoding insulin-like growth factor 2 (IGF2) harbors at 11p15.5 and serves as
      paradigm for an imprinted gene. The IGF2 gene has been demonstrated to be
      imprinted with the paternal allele expressed and the maternal being silent which
      is evolutionally conserved between mice and human. Loss of imprinting (LOI) of
      IGF2 has been demonstrated in a dozen of tumor types including Wilms tumor (WT)
      with a promise of many more to come. The LOI of IGF2 may induce increased or
      deregulated IGF2 expression which could initiate the onset of WT. Thus the LOI of
      IGF2 may provide a novel mechanism of gene activation and play a role in the
      development of a wide range of tumors. This review also discusses other imprinted
      genes on 11p15 which may have a role in WT or other diseases. Finally molecular
      mechanisms of genomic imprinting are discussed.

PMID- 9589903
TI  - Interactions between Epstein-Barr virus and the cell cycle control machinery.
AB  - Epstein-Barr virus (EBV) persists in the majority of the world's human
      population. In the majority of cases the infection is asymptomatic, but EBV is
      associated with a number of human diseases, such as infectious mononucleosis,
      Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, gastric
      carcinomas and other lymphomas and lymphoproliferative diseases. In this review
      the evidence linking EBV with these diseases is reviewed together with recent
      advances in understanding the interactions between EBV and the cell cycle control
      machinery.

PMID- 9589904
TI  - The lymphocyte-dendritic cell system.
AB  - Antigens provoke immune responses. The group of immunocompetent cells related
      directly to this response includes T and B cells, macrophages (M phi) and
      dendritic cells (DCs). DCs acting as antigen-presenting cells have been recently
      recognized to be important in initiating the immune response. B cells and
      follicular dendritic cells (FDCs), the major immunocompetent cells in the B-cell
      dependent area, play an important role in humoral immunity, while T cells and
      interdigitating cells (IDCs), which are the major immunocompetent cells in the T
      cell dependent (TD)-area, play an important role in cellular immunity. The B cell
      IDC interaction in the TD-area is also essential for the B-cell response against
      TD-antigen. Consequently, the lymphocyte-DC interaction is essential in the
      response to antigenic stimulation and in inducing the potent effector cells. B
      cell-DC, T cell-DC and DC-B cell-T cell interactions are regulated in
      predetermined sites by complex and varied mechanisms. Much recent evidence
      demonstrates that DCs modulate lymphocyte biology in its broadest aspects,
      including generation, differentiation, proliferation, and activation. In this
      review, we outline recent studies on the generation, structure, and function of
      lymphatic tissues, propose the concept of the "Lymphocyte-Dendritic Cell System
      (LDS)", and finally describe the significance and functions of this system in
      health and disease.

PMID- 9589902
TI  - Neurotrophins in the developing and regenerating visual system.
AB  - The neurotrophins NGF, BDNF, NT-3 and NT-4 have a wide range of effects in the
      development and regeneration of neural circuits in the visual system of
      vertebrates. This review focuses on the localization and functions of
      neurotrophins in the retina, lateral geniculate nucleus, suprachiasmatic nucleus,
      superior colliculus/optic tectum, and isthmic nuclei. Research of the past 20
      years has shown that neurotrophins and their receptors are localized in numerous
      visual centers from the retina to the visual cortex, and that neurotrophins
      influence proliferation, neurite outgrowth and survival of cells in the visual
      system in vitro and in vivo. A relationship between electrical activity and
      neurotrophic functions has been established in several visual centers in the CNS,
      and neurotrophins have been implicated in synaptic plasticity in the visual
      cortex. Besides functions of neurotrophins as retrograde, target-derived trophic
      factors, recent data indicate that neurotrophins may have anterograde, afferent
      as well as local, paracrine actions in the retina, optic nerve and the visual
      cortex. Some neurotrophins appear to regulate proliferation and survival of glial
      cells in the optic pathways. Neurotrophins increase the survival of retinal
      ganglion cells after axotomy or ischemia and they promote the regeneration of
      retinal ganglion cell axons in some vertebration. Neurotrophins also rescue
      photoreceptors from degeneration. These findings implicate the neurotrophins not
      only as important regulators during development, but also as potential
      therapeutic agents in degenerative retinal diseases and after optic nerve injury.

PMID- 9589905
TI  - Platelet-derived growth factor (PDGF) in primary brain tumours of neuroglial
      origin.
AB  - It has become clear that disruptions in the genome of somatic cells play a
      causative role in tumour development. We know that the ultimate formation of a
      malignancy is the result of a multistep process in which the functional loss
      and/or the altered or increased expression of genes play important roles. One
      such family of genes are the oncogenes, encoding protein products with mainly
      growth stimulating effects. Platelet-derived growth factor (PDGF) belongs to the
      family of oncogenes. It is likely that PDGF plays an essential role in the
      development of at least a subgroup of malignant astrocytic tumours that do not
      contain amplification of the EGF-receptor. The expression of PDGF alpha-receptors
      is related to tumour progression in these tumours, and some of the most malignant
      tumours were shown to contain amplification of the PDGF alpha-receptor. It is
      also clear now from several experimental studies that PDGF can drive the
      transformed phenotype, and that PDGF antagonists, by blocking the PDGF autocrine
      pathway revert the transformed phenotype of certain tumour cells. Because of the
      findings that receptor protein tyrosine kinases such as the EGF- and the PDGF
      receptor play a crucial role in the development of gliomas, it is possible that
      inhibitors of the phosphorylation of the protein tyrosine kinases will be future
      candidates for glioma therapy. They might be able to at least delay the
      development of a fully malignant glioma. The role of PDGF in other tumours of
      neuroglial origin in the central nervous system has not been studied as
      extensively as its role in gliomas. Recent data suggest that also for the
      primitive neuroectodermal tumours overexpression of the PDGF alpha-receptor is
      related to malignancy of the tumours. For other tumours, such as neuroblastomas,
      PDGF exerts a differentiating rather than a mitogenic function and is an
      important survival factor. Further studies are needed to elucidate the role of
      PDGF in these non-glial primary brain tumours. Moreover, for a complete
      understanding of the role of PDGF in malignancies of the CNS, it is important to
      explore its function in the development of the normal CNS further.

PMID- 9589906
TI  - Mechanisms of Bcl-2 protein function.
AB  - The Bcl-2 protein blocks a distal step in an evolutionarily conserved pathway for
      programmed cell death and apoptosis. The gene encoding this protein was first
      discovered because of its involvement in the t(14;18) chromosomal translocations
      commonly found in B-cell lymphomas. Overexpression of Bcl-2 also occurs in many
      other types of human cancers, and prevents cell death induced by nearly all
      anticancer drugs and radiation. Since the discovery of Bcl-2 over ten years ago,
      several cellular and viral homologs have been identified, some of which suppress
      cell death and others which promote apoptosis. Many of these proteins can
      interact with each other through a complex network of homo- and heterodimers.
      Though functionally important, dimerization events still do not explain in a
      broader sense how these proteins actually control cell life and death. Recent
      findings that Bcl-2 can function both as an ion channel and as an adapter or
      docking protein however are beginning to provide insights into the molecular
      mechanisms through which these proteins regulate the programmed cell death
      pathway in normalcy and disease.

PMID- 9589907
TI  - Muller glia cells and their possible roles during retina differentiation in vivo
      and in vitro.
AB  - Muller cells are astrocyte-like radial glia cells which are formed exclusively in
      the retina. Here we present evidence that Muller cells are crucially involved in
      the development of the retina's architecture and circuitry. There is increasing
      evidence that Muller cells are present from the very early beginning of
      retinogenesis. We postulate the "gradual maturation hypothesis of Muller cells".
      According to this hypothesis, Muller cells are continuously generated by a
      gradual transition of neuroepithelial stem cells into mature Muller cells. This
      process may be partly reversible. Muller cells, or their immature precursors, are
      able to subserve different functions. They are primary candidates for stabilizing
      the complex retinal architecture and for providing an orientation scaffold.
      Thereby, they introduce a reference system for the migration and correct
      allocation of neurons. Moreover, they may provide spatial information and
      microenvironmental cues for differentiating neurons, and may also be important
      for the segregation of cell and fibre layers. Additionally, they seem to be
      involved in the guidance of axonal fibres both in radial and in lateral
      directions, as they are involved in the support and stabilization of synapses.

PMID- 9589908
TI  - Enzyme histochemistry of corneal wound healing.
AB  - The usefulness of enzyme histochemical methods for the localization of enzymes as
      catalysts of molecular interactions in the cells and tissues of healing corneal
      wounds is shown in rabbits. The current data on corneal wound healing in humans
      as well as in rabbits with particular reference to serine proteases are reviewed.
      Some inflammatory mediators are also discussed. Plasmin is a serine protease
      which is absent (or present only in very low concentration) in the tear fluid,
      and its activity appears under various pathological conditions in humans or
      following experimental injuries in rabbits. The role of increasing plasmin
      activity in the tear fluid in the depending upon the severity of corneal injury
      is evaluated. Great attention is devoted to conditions leading to long-lasting
      elevated levels of plasmin activity in the tear fluid correlated with corneal
      ulceration. The differences between the histochemical pattern of untreated
      corneas or corneas treated with some serine protease inhibitors are shown, and
      the efficacy of these drugs is discussed in light of present knowledge.

PMID- 9589909
TI  - Diabetic nephropathy: the modulating influence of glucose on transforming factor
      beta production.
AB  - Diabetes in now the commonest cause of renal failure in the western world.
      Furthermore the survival of diabetic patients requiring dialysis treatment for
      renal failure is far less than patients with renal failure secondary to all other
      diseases. It is therefore important to identify the factors that control the
      development of progressive renal disease to allow targeted therapeutic
      interventions which would have major implications both to patient well-being and
      also to the provision of health care world wide. In this review we discuss
      possible metabolic consequences of hyperglycemia and their role in the
      pathogenesis of diabetic nephropathy. We also focus on the involvement of the pro
      fibrotic cytokine Transforming Growth Factor beta, and contrast its role in the
      pathogenesis of glomerular and tubulo-interstitial changes seen in diabetic
      nephropathy.

PMID- 9589911
TI  - Mechanisms of pre-mRNA splicing: classical versus non-classical pathways.
AB  - Expression of genetic information proceeds through two major biological events,
      transcription and translation. However, in eukaryotic cells, the primary
      transcript (pre-mRNA) is not the template that the translational apparatus scans
      through, in order to produce the corresponding protein. Pre-mRNAs undergo several
      modifications (cap site addition, poly A+ tail addition) prior to becoming mature
      mRNAs, with the most important one being the excision (splicing) of the intronic
      sequences. Yet, the mechanisms that regulate the splicing process and the
      generation of alternatively spliced mRNA products are still poorly understood.
      Moreover recent findings suggest that this process also has the capability to
      produce an additional set of RNA products that differ from typical mRNA
      molecules. In these novel RNA transcripts the order of the exons has been changed
      relative to genomic DNA. Furthermore, the properties of these transcripts suggest
      that they may represent circular RNA molecules.

PMID- 9589910
TI  - The induction of gut hyperplasia by phytohaemagglutinin in the diet and
      limitation of tumour growth.
AB  - The growth of a transplantable murine non-Hodgkin lymphoma tumour, developing
      either intraperitoneally as an ascites tumour or subcutaneously as a solid
      tumour, has been shown to be markedly diminished by including phytohaemagglutinin
      (PHA), a lectin present in raw kidney bean (Phaseolus vulgaris) in the diet. In
      NMRI mice fed PHA within the range 0.45-7.0 mg/g diet, tumours which developed
      during a 10 day period after subcutaneous injection of cells were about 35% of
      the dry weight of those in lactalbumin-fed (control) animals. The reduced rate of
      growth occurred in a dose-dependent manner within the range 0.45-3.5 mg/g diet.
      Based on these observations it has been suggested that a competition between the
      gut epithelium undergoing hyperplasia and the developing tumour may occur for
      nutrients from a common body pool, and this may be an important factor with
      regard to the observed initial low level of tumour growth following the feeding
      of a PHA-containing diet. Observations which showed that the level of hyperplasia
      of the small bowel in response to feeding the PHA diets was higher in non
      injected mice compared to those which had been injected with tumour cells
      substantiated the concept of competition between gut and tumour for nutrients
      etc. required for growth. Experiments with a second murine tumour cell line (a
      plasmacytoma) in Balb/c mice gave similar results indicating that the effect of
      PHA was not restricted to a single tumour system.

PMID- 9589913
TI  - [Atherosclerosis].

PMID- 9589912
TI  - Chemopreventive effects of NSAIDs against colorectal cancer: regulation of
      apoptosis and mitosis by COX-1 and COX-2.
AB  - There is a wealth of evidence that nonsteroidal anti-inflammatory drugs (NSAIDs)
      can prevent colorectal cancer. In this article the role of cyclooxygenase 1 and
      2, the principle target of NSAIDs, in the development of colorectal cancer is
      reviewed. Cyclooxygenase is constitutively expressed in normal colonic epithelium
      and surrounding stroma and could catalyse the generation of malondialdehyde which
      is a known mutagen and could initiate colorectal carcinogenesis. Mutation of APC
      which is an early genetic event leads to the expression of cyclooxygenase 2 which
      may prevents the appropriate apoptosis of mutant adenoma cells. Other
      proneoplastic effects of cyclooxygenase include changing the action of
      Transforming Growth Factor beta from anti-proliferative to pro-proliferative,
      reducing adherence to extracellular matrix, promotes metastasis and angiogenesis.
      These properties of cyclooxygenases suggest that inhibition of both isoforms may
      have important protective effects against colorectal cancer.

PMID- 9589914
TI  - [Chronic gastroduodenitis].

PMID- 9589915
TI  - [The role of the renin-angiotensin and kallikrein-kinin systems and of a number
      of hormonal substances in the pathogenesis of the acute period in myocardial
      infarct].

PMID- 9589916
TI  - [The clinicopharmacological properties of nicotinamide].

PMID- 9589917
TI  - [The current concepts of the pathogenesis of glomerulonephritis with hematuria].

PMID- 9589918
TI  - [The characteristics of digestive organ disorders in victims of the Chernobyl
      catastrophe who are undergoing rehabilitation at Truskavets].

PMID- 9589919
TI  - [The late neurological radiation sequelae in participants in the cleanup of the
      accident at the Chernobyl Atomic Electric Power Station].
AB  - As many as 119 subjects who took part in the elimination of the aftermath of the
      Chernobyl Nuclear Power Plant breakdown were studied for their neurological
      status 7-8 years following the accident. Changes were revealed at all levels of
      the brain, such as cortex, subcortex, truncus cerebri. Parameters characterizing
      blood were studied in the examinees together with results of radiometry of brain
      tissue of deceased liquidators, that suggested cause-and-effect relationship
      between cerebral symptomatology and radiation.

PMID- 9589920
TI  - [Nonpsychotic disorders in persons who took part in the cleanup of the aftermath
      of the Chernobyl catastrophe].

PMID- 9589921
TI  - [The effect of ionizing radiation on the organ of vision (a review of the
      literature)].

PMID- 9589922
TI  - [Thyroid diseases and the dynamics of their development in those convalescing
      from acute radiation sickness].
AB  - Patternture was studied together with the time course of development of thyroid
      disorders in 81 patients who had survived acute radiation sickness (ARS) in 1986,
      88 irradiated individuals with unconfirmed ARS diagnosis, and 365 control, by
      results of clinical and laboratory examination carried out in 1989-1993. Increase
      in the incidence of functional disorders, especially that of hypothyrosis in the
      irradiated subjects (4.97% to 6.82%) can be regarded as realization of thyroidal
      non-stochastic effects in the immediate postaccident period.

PMID- 9589923
TI  - [The methodology for the rapid experimental validation of hygienic standards for
      xenobiotics in different environments (2)].
AB  - Based on standards set up in the 1990s correlation and regression analyses were
      performed of relationship between maximum permissible concentration (MPC) of
      xenobiotics in the air of the working environment and their MPCs in the
      atmospheric air, water bodies (with these being recognized as health hazard from
      hygienic-and-toxicological standpoints) or allowable diurnal dose. Highly
      reliable equations of regression were obtained that rely on preliminary
      determination of safe level of exposure in the air of the working environment and
      oral-and-inhalation coefficient on the level of standards set up by results of
      acute and subacute experiments.

PMID- 9589924
TI  - [The effect of heavy metals on the course of pregnancy].

PMID- 9589925
TI  - [The pathogenetic role of the immune and microcirculatory disorders in chronic
      diseases of the hepatobiliary system in women of child-bearing age living in the
      industrial region of the Donets Basin].
AB  - Those people living in industrial regions have increased incidence of chronic
      disorders of the hepatobiliary system. In postpartum female patients presenting
      with the above extragenital pathology, there occur with a greater than usual
      frequency such abnormalities as uterus hypotony, its subinvolution, hypogalactia,
      with the postpartum septic complications running a graver course. Immune
      inadequacies and microcirculatory disorders detected in women presenting with
      chronic disorders of the hepatobiliary system result in the pathological course
      of the postpartum period.

PMID- 9589926
TI  - [The effect of acetylsalicylic acid and streptokinase on the restoration of
      systolic heart function in patients after a myocardial infarct].
AB  - Time course was studied of changes in left ventricular systolic function in those
      patients with prior acute myocardial infarction (AMI) who were exposed to
      thrombolytic therapy and aspirin. A total of 127 AMI patients were examined; they
      were randomized into 3 groups: group I ("A + CK", n = 15) received thrombolytic
      therapy and aspirin; group II ("A", n = 49) were taking aspirin; group III
      (control, n = 63) received neither aspirin nor thrombolytic therapy. All patients
      were evaluated for left ventricular systolic function on the day they entered the
      study, at day 10, 21 and six months later. Both thrombolytic therapy and aspirin
      were found out to accelerate the renewal of left ventricular systolic function in
      AMI patients. Those patients not treated with aspirin and thrombolytics
      experience somewhat slower comeback of indices for left ventricular systolic
      function. Six months of the onset of the condition the values for left
      ventricular systolic function became identical in all groups studied.

PMID- 9589927
TI  - [The therapeutic use of a phosphatide food concentrate in diseases of the
      hepatobiliary system].
AB  - Our studies on phosphatide, a food concentrate, produced as a by-product during
      the extraction of an edible oil in the oil-extraction plants, showed its high
      efficacy in patients (n = 52) with abnormalities of the hepatobiliary system. The
      drug having more than 40 weight percent of phosphorus-containing lipids appeared
      to be efficacious not only in respect of the subjective status of the patients
      but also the functional state of the liver and paraments characterizing lipid
      metabolism.

PMID- 9589928
TI  - [Chemiluminescence in assessing lipid peroxidation function in patients with
      viral hepatitis B and concomitant involvement of the hepatobiliary system].
AB  - 57 patients with viral hepatitis B (VHB) 34 to 62 years old and 43 patients
      suffering from VHB in the presence of chronic hepatobiliary pathologies, their
      age ranging between 37 to 59 years, were examined. Both groups demonstrated
      positive correlation between the level of spontaneous luminescence and malonic
      dialdegide, with the intensity of the induced chemiluminescence correlating with
      the level of dienic conjugates (r = +0.584; r = +0.681).

PMID- 9589929
TI  - [The clinical significance of phasic duodenal intubation and ultrasonic
      monitoring of the gallbladder in healthy subjects].
AB  - Overall twelve essentially healthy subjects were evaluated for the tone and
      contractile function of the gallbladder according to phases of interdigestive
      motility of duodenum as were for effects on these functions of phase-by-phase
      administration of 30 ml of 33% solution of magnesium sulphate. The gallbladder in
      healthy individuals was found out to function according to phases of duodenal
      interdigestive motility and be ready to evacuate bile during phase II. Prior
      diagnostic techniques did not take advantage of interdigestive phase of duodenal
      and gallbladder motility during which phase a standard stimulating agent was
      routinely employed. This can lead to wrong diagnosis of the functional state of
      the biliary tract, gallbladder and their sphincters in the interdigestive period:
      incomplete gallbladder emptying from bile in case the stimulating agent is being
      introduced during phase I or III; hyperdiagnosis of cholecystitis;
      heterodirectivity of the same patient's notion about type of dyskinesias of the
      gallbladder and biliary tract.

PMID- 9589930
TI  - [Antibodies to E. coli and circulating immune complexes in the bile and blood
      serum of patients with suppurative cholangitis].
AB  - It has been found out for the first time that in 55% of cases presenting with
      purulent cholangitis, there are antibodies to a clinical strain of E. coli in the
      bile taken intraoperatively from major bile duct whereas museum specimens of E.
      coli strain are free from the above antibodies. Immune complexes were identified
      in the bile of all examined patients (0.316 +/- 0.085 arbitrary units). In the
      blood serum of patients with purulent cholangitis, antibodies to the clinical
      strain E. coli are not detectable, while there are great counts of circulating
      immune complexes (0.928 +/- 0.242 arbitrary units). Based on the findings
      obtained a conclusion was reached about relative independence of local immunity
      of the biliary tract.

PMID- 9589931
TI  - [The clinical and diagnostic characteristics of perforations in acutely bleeding
      gastroduodenal ulcers].
AB  - Over the period 1982-1996 a total of 8822 patients with ulcerorrhagias were
      treated in a clinical setting. In 122 (1.4%) patients different variants of
      association of perforation of the bleeding ulcers (PBU) were recordable. Features
      of development, course, diagnosis and treatment of PBU patients were studied. Two
      variants of PBU development were identified: concurrently emerging perforation
      with ulcer bleeding--in 34 (27.9%) patients; when perforation of the ulcer
      emerged in 88 (72.1%) in--patients one to seven days following a bleeding event,
      presenting in 48 (54.5%) with bleeding recurrence, and in 40 (45.5%) patients
      without the above recurrence against the background of varying degrees gravity of
      loss of blood. As to PBU localization, 92 (75.4%) patients had the same site (in
      the stomach--18 subjects, pyloroduodenal region--74 ones), 30 (24.6%) patients
      developed simultaneously one perforating gastric or duodenal ulcer and some other
      ulcer bleeding. Analysis of symptoms in PBU and in 474 patients presenting with
      perforating ulcers without bleeding revealed varying degrees atypicalness of PBU
      course depending on variants of combination. A symptom complex of lesser PBU sign
      has been singled out, an algorithm proposed for procedures that might be helpful
      in making early diagnosis and planning surgical treatment to be done in a timely
      fashion. The suggested approach enabled the postoperative mortality to be reduced
      3.5-fold (from 25% to as low as 7.1%).

PMID- 9589932
TI  - [A comparative analysis of the rheographic indices of pancreatic blood flow in
      patients with stomach cancer and varying levels of serum amylase in the
      postoperative period].
AB  - On the basis of findings from rheopancreatography a comparative analysis was done
      of changes in pancreatic bloodflow following radical operations on the stomach in
      patients presenting with elevated and normal levels of blood amilase. Increase in
      the serum amilase activity accompanied a drop in arterial blood filling of
      pancreas together with signs of development of venous plethora of the organ,
      disturbances in microcirculation still observable for more than 10 days following
      the operation.

PMID- 9589933
TI  - [The use of Espumisan in the combined treatment of patients with the meteorism
      symptom].

PMID- 9589934
TI  - [A comparative study of the protective action of a natural surfactant preparation
      in hyperoxia].

PMID- 9589935
TI  - [Antioxidant support and lipid peroxidation in bronchial asthma patients].

PMID- 9589936
TI  - [The dynamic metabolic changes in obstructive bronchitis and in a period of
      somatic well-being in children with lymphatic-hypoplastic diathesis].
AB  - Children during the first few years of their lives, presenting with
      lymphohypoplastic diathesis were studied for their blood serum content of sodium,
      potassium, chlorine. Relationship was found of the electrolyte balance to the
      processes of the lipid peroxidation, activity of the hormonal link of the
      antioxidant defence system.

PMID- 9589937
TI  - [The mobility of the diaphragm in funnel chest deformity studied by ultrasonic
      scanning].
AB  - Overall forty children with funnel chest were studied for mobility of the upper
      cupula of the diaphragm by longitudinal echo scanning of the liver. Quantitative
      data were obtained that may serve as one of the criteria for determining the
      degree of deformity and its progress with time.

PMID- 9589938
TI  - [The experimental results of studying blood chemiluminescence in the diagnosis of
      lung cancer].
AB  - Results of experimental study into intensity and kinetics of chemiluminescence of
      blood correlate with biochemical values for blood and with findings from medical
      examination of patients. The phenomenon of chemiluminescence of blood can be made
      use of in diagnosis of pulmonary cancer.

PMID- 9589940
TI  - [Thrombocytic hemostasis in hemorrhages].
AB  - With the purpose of evaluating the thrombocytic hemostasis in hemorrhages, blood
      platelet function was studied as recommended by Born-O'Brien in patients in the
      early period following the surgical arrest of gastrointestinal hemorrhage.
      Enhanced functional activity of cells was revealed in 88.24% of cases, with
      marked hyperaggregation being recordable in 38.24% of cases and moderate one in
      the others when it revealed itself only with small concentrations of an inductor
      of aggregation being employed. In 11.76% of cases the blood platelets functional
      activity has gotten decreased. When comparing with an analysis of enzymic
      hemostasis and clinical picture of the condition a conclusion was drawn to the
      effect that enhanced functional activity of blood platelets is of compensatory
      and adaptive nature and that it maintains blood hemostatic potential in the pro-
      and anticoagulants dysbalance. Lowering of thrombocytic activity against that
      background can account for recurring nature of hemorrhage.

PMID- 9589939
TI  - [The characteristics of the action of immunodepressive preparations on the killer
      activity of the blood leukocytes in patients with multiple myeloma].
AB  - Overall twenty patients with multiple myeloma (MM) were studied during the
      advanced stage of the disease before the initiation of the cytostatic therapy.
      The results obtained suggest that cytostatic drugs and prednizolon have
      suppressive action on blood leucocyte killer activity. Following in vitro
      vincristin exposure of MM patients' leucocytes cytolytic activity of blood
      leucocyte lymphoid population appeared to be suppressed whereas incubation of
      leucocytes with the solution of cyclophosphane leads to preponderant decrease in
      the killer function of neutrophils. In vitro prednizolon exposure of MM patients'
      leucocytes results in suppression of activity of the antibody-dependent cellular
      cytotoxicity.

PMID- 9589941
TI  - [Mononuclear cells and specific proteins in the tissues of the fetoplacental
      complex during the physiological course of pregnancy and miscarriage].
AB  - Subsets of mononuclear cells, specific pregnancy proteins (SP-1, SP-3, PAPP-A) in
      the normal pregnancy decidua (NPD) and spontaneous abortion decidua (SAD), and
      trophoblast were studied. Significant decrease of lymphocytes infiltration was
      found in SAD. CD8+ cells rather than CD4+ cells predominated in NPD. CD4+ cells
      levels were lower in NPD in comparison with SAD. CD4+ lymphocytes rather than
      CD8+ cells predominated in SAD. Macrophages population was found to be increased
      in SAD in comparison with NPD. In blood vessels walls, cytoplasm of mononuclear
      cells and decidua stroma, PAPP-A and SP-3 were expressed in NPD and unexpressed
      or negative in SAD. In syncytiotrophoblast, SP-1 was expressed in normal
      pregnancy and unexpressed in spontaneous abortion. It is suggested that
      inadequate fetal-placental tissues counts of suppressor decidual lymphocytes,
      specific pregnancy proteins might be a cause of early spontaneous abortion.

PMID- 9589942
TI  - [The prognostic significance of the ultrasonic study of osmophilic lamellar
      myelin bodies in chronic cystitis and transitional-cell bladder tumors].
AB  - Electron microscopy studies revealed three possibilities in the formation of
      osmophilic lamellar myelin figures and indicated ways for their elimination. In
      health states and in transitional cell papillomas, low-grade transitional cell
      carcinoma of urinary bladder, the osmophilic lamellar myelin figures are
      comparatively less common. In chronic cystitis, high-grade transitional cell
      carcinoma of the urinary bladder as well as in moderately malignant and non
      differentiable ones, the osmophilic lamellar myelin figures counts get markedly
      increased, which fact suggests that the study of the above figures may have both
      general biological as well as differential diagnostic and prognostic
      significance.

PMID- 9589943
TI  - [The pathogenesis of infertility in men].
AB  - With the purpose of gaining insights into the general regularities and particular
      features of pathogenesis of sterility of urogenital genesis, we undertook the
      present studies on biopsy specimens of testes, epididymis, deferent ducts,
      prostate, spermogramme, blood plasma content of gonadotrophic and sex hormones in
      162 patients with infertility of urogenital genesis, and in 412 rats. Infertility
      pathogenesis was found out to have two stages: compensatory-adaptive alterations
      and irreversible disorders. Infertility is believed to be a polyetiologic,
      monopathogenetic medical condition.

PMID- 9589944
TI  - [The sequelae of a mild closed craniocerebral trauma and the prognosis of its
      late outcomes in patients with a unfavorable preinjury background].
AB  - Combined catamnestic studies were made in 310 individuals 16 to 80 years old with
      a history of mild closed craniocerebral injury (MCCCI) for their health status.
      Of these, 200 subjects had, prior to MCCCI, arterial hypertension, chronic first
      second degree cerebrovascular insufficiency, gastric and duodenal ulcer, chronic
      cholecystitis, hepatocholecystitis, gastroduodenitis. In a catamnestic follow-up
      1 year following MCCCI many patients exhibited abnormal psychoneurologic and
      vegetovisceral changes. Prognostic factors have been derived for late outcomes of
      MCCCI using A. Val'd's sequential analysis.

PMID- 9589945
TI  - [The cyclic nature of exacerbation-remission in immunopathology and its
      significance for clinical medicine].

PMID- 9589946
TI  - [The use of the alpha-glucosidase inhibitor acarbose for the treatment of type-2
      diabetes mellitus in secondary sulfanilamide resistance].
AB  - Efficacy was studied of acarbose in patients with type II diabetes mellitus
      during the development of secondary sulfamide resistance. 63 patients were
      evaluated. Studies were made involving glycemia on an empty stomach, postprandial
      glycemia and 24-h glucosuria in order that we might learn about the above drug's
      efficacy. High confidence level decrease in postprandial glycemia was recorded as
      was significant reduction in diurnal glucosuria.

PMID- 9589947
TI  - [The organ-conserving treatment of breast cancer patients].

PMID- 9589948
TI  - [Psychoautonomic disorders in patients with neurocirculatory dystonia and the
      mitral valve prolapse syndrome].
AB  - Pattern was studied of autonomic regulation of cardiac activity in young male
      adults with mitral valve prolapse (MVP) versus patients with cardiac type of
      neurocirculatory dystonia (NCD). In assessing the condition of the autonomic
      nervous system we employed statistical analysis of heart rate at rest (vegetative
      tone) and at minute 60 of the intake of propranolol (vegetative reactivity). The
      patient's psychological state was assessed by MMPI. MVP patients had normal
      vegetative homeostasis but hyperreactivity of the autonomic nervous system in
      acute propranolol test; symptomatic patients displayed paradoxical reactions. NCD
      patients showed sympatheticotonia in rest and normoreactivity in acute
      propranolol test. We conclude that above patient populations experienced notable
      changes in their mental condition that reflect disturbances in the personality
      formation process.

PMID- 9589949
TI  - [The level of somatotropic hormone and cortisol in the blood of patients with
      ischemic heart disease and a rhythm disorder].
AB  - Overall ninety-six ChIHD patients presenting with disturbances of cardiac rhythm
      were evaluated by radioimmunologic technique for blood content of somatotrophic
      hormone (STH) and hydrocortisone. In ChIHD patients presenting with extrasystolic
      arrhythmia, basal STH blood levels tend towards getting decreased, those of
      hydrocortisone increased. On dispelling extrasystole, blood STH content gets
      increased, with hydrocortisone levels remaining elevated. Recordable in ChIHD
      with invariable form of cardiac fibrillation are unchanged STH basal levels and
      increased content of hydrocortisone in blood.

PMID- 9589950
TI  - [The comparative efficacy of using Espumisan and carboenterosorbent in patients
      with the irritable bowel syndrome].

PMID- 9589951
TI  - [The antibiotic sensitivity of Staphylococcus aureus--the causative agent of
      chronic tonsillitis and pharyngitis--in gastroenterology patients].
AB  - Sensitivity was studied to fifteen antibiotics of different members of
      Staphylococcus aureus group of bacteria recovered from the mucous coats of the
      palatine tonsils, throat, in twenty seven patients with gastroduodenitis, 21
      those with duodenal ulcer, 12 patients with other gastroenterological disorders,
      and 17 essentially healthy carriers of above micro-organisms. The pathogens
      causing tonsillopharyngitis in the patients appeared to be significantly less
      sensitive to seven antibiotics than they were in controls. Polyresistance to
      antibiotics is a sign of a higher virulence. It is conceivable that
      staphylococcus has a part in the pathogenesis of harmful changes in the tissues
      of the gastroduodenal zone.

PMID- 9589952
TI  - [The use of prolonged-action antimicrobial preparations in the combined treatment
      of generalized periodontitis].

PMID- 9589953
TI  - [Traditional and "lesser" hemosorption in the treatment of bronchial asthma
      patients].
AB  - Based on a comprehensive comparative characterization relying on clinical,
      functional and allergological indices in 110 patients with bronchial asthma, a
      conclusion was drawn to the effect that traditional hemosorption (HS) involving
      the use of a sorbent 400 ml in capacity is more efficient procedure than commonly
      named "lesser" hemosorption with a 100 ml capacity sorbent. It is advisable that
      in patients with bronchial asthma, HS should be done only with 400 ml volume
      sorbents.

PMID- 9589954
TI  - [The efficacy of pneumocalorimetry for the quantitative evaluation of treatment
      results in patients with pneumoconiosis and rheumocarditis].
AB  - The respiratory system conditioning function (CFRS) was evaluated with the aid of
      pneumocalorimetry by taking account of respiratory thermic losses spent to warm
      breathing air in the volume of vital capacity. There were 100 patients with
      pneumoconiosis and 49 ones with rheumatic carditis. In the course of treatment of
      patients with pneumoconiosis, both occurrence and degree of insufficiency of the
      conditioning function (CF) got decreased, with reduction in CF insufficiency
      degree being 60% in those patients faring well owing to the treatments
      administered, and 40% in those not having benefited much from the treatment. 73%
      of patients with rheumatic carditis experienced, under the influence of the
      treatment received, decline in the degree of CF insufficiency. Thus,
      pneumocalorimetric criterion described above will, we believe, help in
      quantitating the efficiency of treatment of CF insufficiency.

PMID- 9589955
TI  - [The assessment of the efficacy of calcium antagonists in the treatment of
      children with repeated episodes of the broncho-obstructive syndrome].
AB  - Overall seventy-five schoolchildren with a history of no less than 4 episodes of
      impassability commonly against the afebrile background were examined. The results
      obtained suggest that the greatest reduction in the relative risk of bronchial
      unspecific hyperreactivity manifestations with calcium antagonists being ingested
      occurs in those children experiencing recurrent episodes of bronchial obstruction
      in the presence of marked lability of the bronchi that is commonly associated
      with the atopic genesis of their obstruction.

PMID- 9589956
TI  - [The treatment of benign prostatic hyperplasia using the Mumie-Vitas
      preparation].
AB  - Overall thirty-eight patients presenting with stage I-II benign prostate
      hyperplasia received treatment with a new local drug preparation Mumiyo-Vitas,
      0.2 g on a once- or twice-daily basis over six months. Effects were studied of
      the drug on the urologic symptomatology and quality of life of patients
      presenting with ongoing micturitional disturbances, functional state of detrusor
      vesicae, prostate volume and urethral resistance. Efficiency of the treatment
      given was assessed by the International system, uroflowmetry, ultrasonic
      investigation. Mumiyo-Vitas appeared to be of therapeutic benefit in those
      patients with subjective and objective symptoms of the urinary bladder
      obstruction who had innocent prostate hyperplasia.

PMID- 9589957
TI  - [The effect of tanakan on central nervous system function in patients with the
      residual manifestations of stroke].

PMID- 9589958
TI  - [The main locations of post-stroke cysts in the cerebral hemispheres and the
      clinical characteristics of the motor deficit (based on computed tomographic
      data)].
AB  - Overall eighty-eight patients with hemispheric stroke were examined 3 months
      following the outset of the disease. Clinical findings and computerized
      tomography scans showed the cerebral hemispheric cysts to be in
      posterocapsulolenticular, anterocapsulocaudal, lenticular, thalamic, lobar,
      frontal, combined, multiple positions. Locations of hemispheric cysts were found
      out to be associated with polymorphous structure of motor deficit.

PMID- 9589959
TI  - [The treatment of endogenous depression by micropolarization of the brain].

PMID- 9589960
TI  - [Cerebrolysin in neurological and psychiatric practice].

PMID- 9589961
TI  - [The pathogenetic treatment of alcoholism].
AB  - Overall ninety-seven male subjects suffering from stage-II alcoholism were
      studied for effects of verapamil on pathologic drawing toward alcohol. The above
      drug proved to be very effective in the treatment of alcoholism, which fact might
      be accounted for by certain confunction of membrane depolarization in the release
      of dopamine.

PMID- 9589962
TI  - [The importance of an in-depth study of visual functions in patients with a
      traumatic carotid-cavernous fistula].
AB  - As many as 78 patients with traumatic carotid-cavernous fistula were examined.
      Apart from routine clinical examination we determined th flickering fusion
      frequency, pupil cycle time; we employed visocontrastoperimetry and fluorescent
      angiography to identify early disturbances in visual functions and allow some
      judgement about time course of changes in the preoperative and postoperative
      course of the condition. This should help us in dealing efficiently with visual
      disorders.

PMID- 9589963
TI  - [The clinicoimmunological evaluation of the use of timogeksin in different forms
      of measles].
AB  - Materials are submitted concerning the use of thymohexine in the treatment of
      measles. Efficacy of thymohexine in 133 children with grave and complicated forms
      of measles was assessed. Thymohexine was found out to reduce the duration of the
      infectious toxicosis and local inflammatory events. Under the influence of the
      above drug the total counts of T- and B-lymphocytes (CD11, CD8, CD4, CD22)
      returned to normal as did the immunoregulatory index (D4/CD8), levels of
      circulating immune complexes, their molecular composition.

PMID- 9589964
TI  - [The level of immunoglobulins and antispermatic antibodies in the cervical mucus
      of infertile women with cervix uteri pathology].
AB  - This article is about determination of local immunity indices, immunoglobulins of
      A, M, G, sIgA classes and antispermal immunity of the cervical mucus in infertile
      women with pathology of cervix uteri. It is shown that usage of complex tests
      with local immunity as well as identification antispermal antibody should be a
      reliable basis to diagnose infertile women with benign and precancerous diseases
      of cervix uteri.

PMID- 9589965
TI  - [The pathogenetic characteristics and treatment of erysipelas in diabetics].
AB  - Pathogenetic role was studied of lipid peroxidation (LPO) in 65 patients with
      erysipelas with concurrent diabetes mellitus (DM) versus a group of 86 patients
      without DM. In the former case, significant increase in blood plasma
      hydroperoxides, such as malonic dialdegide and dienic conjugates, was recordable,
      which fact suggested activation of LPO processes. Positive correlation was
      established between blood content of hydroperoxides and levels of circulating
      immune complexes. A complex of drugs endowed with known antioxidant, anti
      inflammatory and immunocorrective activity were found to have a beneficial effect
      on clinical, immune and biochemical indices.

PMID- 9589966
TI  - [Reform of the financing mechanism of public health].

PMID- 9589967
TI  - [Tuberculosis--a global problem].
AB  - The author presents an analysis of health hazard conditions with respect to
      tuberculosis in the world and in Ukraine in particular. It is shown that
      epidemiologic situation with tuberculosis is getting worse in Ukraine, with the
      reasons for this negative dynamics being pointed out. Regimes of
      antimycobacterial therapy of different clinical forms of pulmonary and
      extrapulmonary tuberculosis are elucidated as to recommendations of the World
      Health Organization. Criteria by which clinical efficiency can be measured were
      established as were treatment options for tuberculosis.

PMID- 9589968
TI  - [The management of the functioning of the home hospital department of a
      therapeutic polyclinic].

PMID- 9589969
TI  - [The organizational characteristics of hospital medical care for World War II
      veterans and elderly persons].

PMID- 9589970
TI  - [A mathematical assessment of the efficacy of the methods for treating patients
      with chronic nonspecific lung diseases at a health resort].
AB  - A total of 866 patients with chronic unspecific lung diseases were examined.
      Medical data collection, storage and acquisition involved making use of the
      operational system UNIX as well as data base control systems UBASE and INFORMIX.
      Relation was found out between use rate of bronchodilators, antibacterial drugs,
      corticosteroids, and results of treatment. The above patients can also derive
      benefit from such nonpharmacologic modes of treatment as apparatus-aided training
      of breathing, hypoxia and hypercapnia training, acupuncture-laser therapy
      treatments, herbal aromatic substances.

PMID- 9589972
TI  - [The use of acupuncture reflexotherapy in treating patients with rheumatoid
      arthritis].
AB  - Efficiency was studied of multi-modality treatment of rheumatoid arthritis (RA)
      involving acupuncture (A). Indices were assessed for the number of the inflamed
      joints, the joint index, duration of the morning rigidity and visual scale of
      pain. Combined treatment of RA using A was found to more effectively lower the
      values for the joint index and visual scale of pain. A conclusion was reached to
      the effect that A may improve results of drug treatment.

PMID- 9589971
TI  - [Phytotherapy as a reliable natural means of treating patients with type-2
      diabetes mellitus].

PMID- 9589974
TI  - [Carbohydrates: perspective].

PMID- 9589973
TI  - [Improvement in the program and methods of conducting an internship in
      occupational hygiene].
AB  - The authors describe their experience gained with conducting internship training
      in occupational hygiene for graduating students of medical and prophylaxis
      departments of medical colleges. Special attention is called to the matter of
      learning by those engaged in internship studies of practical skills of work of a
      physician-occupational hygienist relating, in particular, to exercising sanitary
      inspection, both preventive and running, in industrial settings. Measures were
      proposed to improve the programme and curriculum to be guided by in conducting
      the above internship training.

PMID- 9589975
TI  - [Selective disaccharidase deficiency].

PMID- 9589976
TI  - [Congenital amylase deficiency].

PMID- 9589977
TI  - [Galactose-1-phosphate uridyltransferase deficiency].

PMID- 9589978
TI  - [Galactokinase deficiency].

PMID- 9589979
TI  - [UDP-galactose-4-epimerase deficiency].

PMID- 9589980
TI  - [Hypergalactosaemia by congenital portosystemic venous shunt].

PMID- 9589981
TI  - [Glycogen storage disease type Ia, Ic and Id].

PMID- 9589982
TI  - [Glycogen storage disease type Ib].

PMID- 9589983
TI  - [Glycogen debranching enzyme deficiency].

PMID- 9589984
TI  - [Glycogenosis type IV (branching enzyme deficiency, amylopectinosis, Andersen
      disease, polyglucosan body disease)].

PMID- 9589986
TI  - [Glycogenosis type VI (hepatic phosphorylase deficiency, Hers disease].

PMID- 9589985
TI  - [Glycogenosis type V (muscle phosphorylase deficiency)].

PMID- 9589987
TI  - [Type VII glycogen storage disease].

PMID- 9589988
TI  - [Glycogen storage disease type VIII].

PMID- 9589989
TI  - [Glycogen synthase deficiency].

PMID- 9589990
TI  - [Phosphoglucomutase deficiency].

PMID- 9589991
TI  - [Hepatic glycogenosis with renal Fanconi syndrome].

PMID- 9589992
TI  - [Phosphoglycerate kinase deficiency].

PMID- 9589993
TI  - [Phosphoglycerate mutase deficiency].

PMID- 9589994
TI  - [Lactic dehydrogenase deficiency].

PMID- 9589995
TI  - [Essential fructosuria (hepatic fructokinase deficiency)].

PMID- 9589996
TI  - [Hereditary fructose intolerance].

PMID- 9589997
TI  - [Fructose-1,6-bisphosphatase deficiency].

PMID- 9589998
TI  - [D-glycerate kinase D-glyceric aciduria].

PMID- 9589999
TI  - [Incomplete fructose absorption (transport)].

PMID- 9590000
TI  - [Congenital sucrosuria].

PMID- 9590002
TI  - [Inborn error of amino acids metabolism--general aspect].

PMID- 9590001
TI  - [Essential pentosuria].

PMID- 9590003
TI  - [Phenylketonuria (phenylalanine hydroxylase deficiency)].

PMID- 9590004
TI  - [Maternal phenylketonuria].

PMID- 9590005
TI  - [Disorders of tetrahydrobiopterin homeostasis].

PMID- 9590006
TI  - [Hereditary tyrosinemia type I].

PMID- 9590007
TI  - [Hereditary tyrosinemia type II].

PMID- 9590008
TI  - [Hereditary tyrosinemia type III].

PMID- 9590009
TI  - [Hawkinsinuria].

PMID- 9590010
TI  - [Other abnormalities of tyrosine metabolism].

PMID- 9590011
TI  - [Histidinemia].

PMID- 9590012
TI  - [Urocanic aciduria (urocanase deficiency)].

PMID- 9590013
TI  - [Hyperprolinemia type I].

PMID- 9590014
TI  - [Hyperprolinemia type II].

PMID- 9590015
TI  - [Hydroxyprolinemia].

PMID- 9590016
TI  - [Prolidase deficiency].

PMID- 9590017
TI  - [Gyrate atrophy of the choroid and retina].

PMID- 9590018
TI  - [Carbamyl phosphate synthetase I deficiency].

PMID- 9590019
TI  - [Ornithine transcarbamylase deficiency (OTCD)].

PMID- 9590020
TI  - [Argininosuccinate synthetase deficiency].

PMID- 9590021
TI  - [Argininosuccinate lyase deficiency].

PMID- 9590022
TI  - [Arginase deficiency].

PMID- 9590023
TI  - [Hyperornithinemia-hyperammonemia-homocitrullinuria (H.H.H.) syndrome].

PMID- 9590024
TI  - [Familial hyperlysinemia(alpha-aminoadipic semialdehyde synthase defect)].

PMID- 9590025
TI  - [Saccharopinuria (a variant form of familial hyperlysinemia)].

PMID- 9590026
TI  - [Hypervalinemia].

PMID- 9590027
TI  - [Hyperleucinisoleucinemia].

PMID- 9590028
TI  - [Maple syrup urine disease].

PMID- 9590029
TI  - [Disorders of transsulfuration; disorders of sulfur-aminoacids metabolism].

PMID- 9590030
TI  - [Sarcosine dehydrogenase deficiency].

PMID- 9590031
TI  - [Sarcosinemia associated with folate deficiency].

PMID- 9590032
TI  - [Nonketotic hyperglycinemia].

PMID- 9590033
TI  - [Dihydropyrimidinase deficiency (dihydropyrimidinuria)].

PMID- 9590034
TI  - [Hyperbetaalaninemia].

PMID- 9590035
TI  - [Malonic, methylmalonic and ethylmalonic acid semialdehyde dehydrogenase
      deficiency].

PMID- 9590036
TI  - [beta-Aminoisobutyricaciduria].

PMID- 9590037
TI  - [Pyridoxine dependency with seizures].

PMID- 9590038
TI  - [gamma-Aminobutyric acid transaminase deficiency].

PMID- 9590039
TI  - [4-Hydroxybutyric aciduria].

PMID- 9590040
TI  - [Serum carnosinase deficiency and homocarnosinosis].

PMID- 9590041
TI  - [Kynureninase deficiency].

PMID- 9590042
TI  - [Organic acidemia: outline].

PMID- 9590043
TI  - [N5-methyltetrahydrofolate: homocysteine methyltransferase deficiency].

PMID- 9590044
TI  - [Isolated methylmalonyl-CoA mutase deficiency].

PMID- 9590045
TI  - [Defects in adenosylcobalamin biosynthesis].

PMID- 9590046
TI  - [Propionic acidemia].

PMID- 9590047
TI  - [Isovaleric acidemia].

PMID- 9590048
TI  - [3-Methylcrotonyl-CoA carboxylase deficiency].

PMID- 9590049
TI  - [3-Methylglutaconyl-CoA hydratase deficiency].

PMID- 9590050
TI  - [X-linked 3-methylglutaconic aciduria (normal hydratase)].

PMID- 9590051
TI  - [Methylglutaconic aciduria (normal hydratase, unspecified)].

PMID- 9590052
TI  - [3-Hydroxy-3-methylglutaryl-CoA-lyase deficiency].

PMID- 9590053
TI  - [Mevalonic aciduria].

PMID- 9590054
TI  - [Mitochondrial acetoacetyl-CoA thiolase deficiency].

PMID- 9590055
TI  - [3-Hydroxyisobutyryl-CoA deacylase deficiency].

PMID- 9590056
TI  - [3-Hydroxyisobutyric aciduria (3-hydroxyisobutyric acid dehydrogenase
      deficiency)].

PMID- 9590057
TI  - [Methylmalonic semialdehyde dehydrogenase deficiency].

PMID- 9590058
TI  - [2-Methylbranched chain acyl-CoA-dehydrogenase deficiency].

PMID- 9590059
TI  - [Alkaptonuria (homogentisic aciduria)].

PMID- 9590060
TI  - [Glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I)].

PMID- 9590061
TI  - [2-Ketoadipic dehydrogenase deficiency (2-ketoadipic acidemia)].

PMID- 9590062
TI  - [Pyruvate decarboxylase deficiency].

PMID- 9590064
TI  - [Pyruvate dehydrogenase phosphatase deficiency].

PMID- 9590063
TI  - [Lipoamide dehydrogenase deficiency].

PMID- 9590065
TI  - [Pyruvate carboxylase deficiency].

PMID- 9590066
TI  - [Phosphoenolpyruvate carboxykinase deficiency].

PMID- 9590067
TI  - [Fumarase deficiency].

PMID- 9590068
TI  - [Succinyl-CoA: 3-ketoacid CoA transferase deficiency].

PMID- 9590069
TI  - [Cytosolic acetoacetyl-CoA thiolase deficiency].

PMID- 9590070
TI  - [Glutaric aciduria type 2].

PMID- 9590071
TI  - [5-Oxoprolinase deficiency].

PMID- 9590072
TI  - [Biochemical and molecular bases of glutathione synthetase deficiency].

PMID- 9590073
TI  - [gamma-Glutamyl cysteine synthetase deficiency].

PMID- 9590074
TI  - [gamma-Glutamyl transpeptidase deficiency].

PMID- 9590075
TI  - [Adenosine triphosphate: glycerol 3-phosphotransferase deficiency].

PMID- 9590076
TI  - [Glycerol intolerance].

PMID- 9590077
TI  - [Canavan disease (aspartoacylase deficiency)].

PMID- 9590079
TI  - [L-2-hydroxyglutaric aciduria].

PMID- 9590078
TI  - [D-2-hydroxyglutaric aciduria].

PMID- 9590080
TI  - [Primary hyperoxaluria type 2(PH2)].

PMID- 9590081
TI  - [Carnitine transporter defect].

PMID- 9590082
TI  - [Carnitine palmitoyltransferase I(CPT1) deficiency].

PMID- 9590083
TI  - [Carnitine/acylcarnitine translocase deficiency].

PMID- 9590084
TI  - [Carnitine palmitoyltransferase II(CPT2) deficiency].

PMID- 9590085
TI  - [Very long-chain (and long-chain) acyl-CoA dehydrogenase deficiency].

PMID- 9590086
TI  - [2,4-Dienoyl-CoA reductase deficiency].

PMID- 9590087
TI  - [Medium-chain acyl-CoA dehydrogenase deficiency].

PMID- 9590089
TI  - [Short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency].

PMID- 9590088
TI  - [Short-chain acyl-CoA dehydrogenase (SCAD) deficiency].

PMID- 9590090
TI  - [Mitochondrial trifunctional protein (TP) deficiency].

PMID- 9590091
TI  - [Overview on inborn errors of purine and pyrimidine metabolism].

PMID- 9590093
TI  - [PRPP synthetase deficiency].

PMID- 9590092
TI  - [5-Phosphoribosyl-1-pyrophosphate synthetase overexpression].

PMID- 9590094
TI  - [Abnormality of amidophosphoribosyltransferase].

PMID- 9590095
TI  - [Adenylosuccinase deficiency].

PMID- 9590096
TI  - [Purine ecto-5'-nucleotidase deficiency].

PMID- 9590097
TI  - [AMP deaminase deficiency].

PMID- 9590098
TI  - [Myoadenylate deaminase deficiency].

PMID- 9590099
TI  - [Adenosine deaminase (ADA) deficiency, partial ADA deficiency].

PMID- 9590100
TI  - [Purine nucleoside phosphorylase (PNP) deficiency].

PMID- 9590101
TI  - [Hypoxanthine-guanine phosphoribosyltransferase deficiency].

PMID- 9590102
TI  - [Adenine phosphoribosyltransferase (APRT) deficiency].

PMID- 9590103
TI  - [2,8-Dihydroxyadenine lithiasis].

PMID- 9590104
TI  - [Classical xanthinuria (type I and II)].

PMID- 9590105
TI  - [Molybdenum cofactor deficiency].

PMID- 9590106
TI  - [Gout due to disorder of urate binding proteins (the urate-binding alpha 1-2
      globulin deficiency)].

PMID- 9590107
TI  - [Familial juvenile gouty nephropathy].

PMID- 9590108
TI  - [Hereditary orotic aciduria].

PMID- 9590110
TI  - [Dihydropyrimidine dehydrogenase deficiency].

PMID- 9590109
TI  - [Pyrimidine-5'-nucleotidase deficiency].

PMID- 9590111
TI  - [Xeroderma pigmentosum].

PMID- 9590112
TI  - [Bloom's syndrome].

PMID- 9590113
TI  - [Cockayne syndrome].

PMID- 9590114
TI  - [Fanconi anemia].

PMID- 9590115
TI  - [Fragile X syndrome].

PMID- 9590116
TI  - Cell adhesion molecule Nr-CAM is over-expressed in human brain tumors.
AB  - Using the technique of differential display-polymerase chain reaction (DD-PCR),
      we isolated a cDNA fragment that is over-expressed in glioblastoma multiforme
      tissue as compared to normal brain tissue. Sequence analysis indicated that this
      sequence is identical to the previously isolated human neuron-glia-related cell
      adhesion molecule hNr-CAM. Gene-specific RT-PCR analysis indicated that hNr-CAM
      is over-expressed in high-grade astrocytomas, gliomas and glioblastoma tumor
      tissues as compared to normal brain tissue. High levels of hNr-CAM expression
      also were observed in cell lines derived from astrocytomas, gliomas and
      glioblastoma multiforme tumors. Low levels of hNr-CAM expression were observed in
      neuroblastoma, meningiomas, melanoma, normal breast and prostate tumor tissues.
      Northern blot analysis showed an alternatively spliced mRNA of 1.4 kb in several
      tumors as compared to the 7.5 kb transcript found in normal brain tissue. Genomic
      Southern blot analysis of DNA from 3 brain tumor cell lines showed that over
      expression of hNr-CAM in brain tumors was not due to gene amplification. In situ
      hybridization analysis indicated that 11 of the 20 human brain tumor samples
      studied showed hNr-CAM over-expression. Our results suggest that hNr-CAM is over
      expressed in malignant brain tumors and can serve as a novel marker for brain
      tumor detection and perhaps therapy.

PMID- 9590117
TI  - Cytoplasmic staining of c-erbB-2 is not associated with the presence of
      detectable c-erbB-2 mRNA in breast cancer specimens.
AB  - The cell-surface receptor tyrosine kinase protein c-erbB-2 is
      immunocytochemically detected as membrane staining on the surface of cancer cells
      in 20-30% of cases of breast cancer, and its presence has been associated with
      poor prognosis for the patient. However, there have been numerous reports of
      immunocytochemical staining for c-erbB-2 solely in the cytoplasm of some normal
      and tumour specimens with frequently used anti-sera, and the presence of such
      staining has been difficult to interpret. It is not known for certain that
      cytoplasmic c-erbB-2 staining is an artefact of the immunocytochemical procedures
      used. Thus, mRNA for c-erbB-2 has been quantified in tumours exhibiting only
      cytoplasmic staining or varying levels of membrane staining using a sensitive,
      competitive PCR method. Whereas abundant levels of c-erbB-2 mRNA are found in
      tumours exhibiting membrane staining for c-erbB-2 and these levels correlate with
      the percentage of tumour cells showing membranous staining for c-erbB-2, the
      level of c-erbB-2 mRNA in tumours displaying only cytoplasmic staining is no
      higher than in c-erbB-2-negative specimens.

PMID- 9590118
TI  - Over-expression of epidermal growth factor receptor and c-erbB2/neu but not of
      int-2 genes in benign prostatic hyperplasia by means of semi-quantitative PCR.
AB  - It is well established that activation of cellular genes may trigger uncontrolled
      cell growth and cancer development. Previous reports suggest that the epidermal
      growth factor receptor (EGFr), c-erbB2/neu and int-2, fibroblast growth factor-3,
      may be implicated in the development of benign prostatic hyperplasia (BPH). Using
      the polymerase chain reaction technique, we have assessed the amplification and
      expression of these molecular markers in 30 prostate samples from patients with
      BPH as well as from 5 normal donors. We detected mRNA over-expression of EGFr and
      c-erbB2/neu in 36% and 63%, respectively, of the BPH samples, but no gene
      amplification was found. No amplification or over-expression of int-2 was
      detected in any of the samples analyzed, suggesting that int-2 is not involved in
      BPH. Our results thus suggest a role for EGFr and c-erbB2/neu but not for int-2
      in the development of BPH.

PMID- 9590119
TI  - Family aggregation of carcinoma of the hypopharynx and cervical esophagus:
      special reference to multiplicity of cancer in upper aerodigestive tract.
AB  - The role of family history in the multiple occurrence of cancer in the upper
      aerodigestive tract (UADT) remains unclear. The family histories of close
      relatives were examined in 167 patients with either hypopharyngeal or cervical
      esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases.
      The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT
      cancers. Based on the family histories of close relatives, 167 cases with PhCe
      cancer were divided into 3 groups (Group I, 18 cases with a family history of
      UADT cancer; Group II, 37 cases with a family history of other cancers; Group
      III, 112 cases with no family history of any cancers). The mean age of the cases
      in group I was 59.4, which was younger than in group III (64.2). Second primary
      squamous-cell carcinomas in the UADT were more frequently recognized in group I
      (39%) than in group III (11%). However, no differences were observed in the
      smoking and drinking habits of male patients between each group. These results
      thus suggest that a family history of UADT cancers appears to be associated with
      the multiple occurrence of UADT cancers as well as the development of PhCe
      cancer.

PMID- 9590120
TI  - Cancer incidence in Ho Chi Minh City, Viet Nam, 1995-1996.
AB  - The results from the population-based cancer registry for the city of Ho Chi Minh
      in 1995-1996 represent the first information on the incidence of cancer in
      southern Viet Nam. A total of 4,080 cancer cases in males and 4,338 in females
      were registered, corresponding to age-standardized incidence rates (ASRs) of
      130.9 per 100,000 in men and 100.7 per 100,000 in women. As elsewhere in South
      East Asia, the principal cancer of men was liver cancer (ASR 25.3), with
      moderately high rates of lung cancer (ASR 24.6) and stomach cancer (ASR 16.5);
      cancer of the penis, reportedly very common in early case series from Viet Nam,
      is now rarely seen. In women, cervical cancer was the dominant malignancy (ASR
      26.0) followed by breast cancer (ASR 12.2) and stomach cancer (ASR 7.5). Although
      there may be some under-registration in these early years of operation, the
      recorded rates of cervical cancer and liver cancer are already high and suggest
      that southern Viet Nam would benefit from an effective cervical cancer screening
      programme, as well as efforts to interrupt the transmission of hepatitis B virus
      to reduce liver cancer incidence and effective anti-smoking programs.

PMID- 9590121
TI  - Human papillomavirus and human immunodeficiency virus infections: relation with
      cervical dysplasia-neoplasia in African women.
AB  - Our study assessed the factors associated with cervical squamous intra-epithelial
      lesions (SILs) and invasive cervical cancer, with special attention to human
      immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. Women
      from 3 outpatient gynecology clinics of Abidjan, Cote d'Ivoire, were screened for
      cervical abnormalities: 151 women with low-grade SILs and 151 controls, 60 with
      high-grade SILs and 240 controls, and 13 with invasive cancer and 65 controls
      were enrolled in 3 case-control studies. Controls were chosen at random among the
      women without lesions, with a frequency matching for age and center. We used the
      PCR method for the detection of cervical HPV DNA and the restriction fragment
      length polymorphism analysis for HPV typing. HIV antibody testing and CD4 cell
      count were performed. In multivariate analyses, factors associated with cervical
      lesions were: for low-grade SILs, HPV positivity, HIV-1 seropositivity and parity
      >3; for high-grade SILs, HPV positivity, chewing tobacco, HIV-1 seropositivity
      and illiteracy, and for invasive cancer, HPV positivity only. We found a
      diversity of HPV types associated with SILs. In HIV-1-infected women, SILs
      occurred at an early stage of HIV disease. Women infected with both HIV-1 and HPV
      were at much higher risk of SILs than women infected with each of these 2 viruses
      separately. Invasive cancer was linked to HIV-2 infection in univariate analysis
      only. Our results suggest that the relation of SILs with HIV-1 infection is
      mainly explained by HPV infection and that HIV-1-infected African women may not
      often reach the invasive stage of cervical cancer.

PMID- 9590122
TI  - Epithelial expression of glycodelin in biphasic synovial sarcomas.
AB  - Glycodelin is a 28 kDa glycoprotein of the lipocalin family that was previously
      considered to be specific for the reproductive tract. Glycodelin is found in the
      secretory glandular epithelium of endometrium and in seminal vesicles. Given the
      cyclic differentiation of normal endometrial epithelium, we studied by
      immunohistochemistry a possible expression of glycodelin in other tissues
      displaying stroma-to-epithelium maturation. We report here that 11/11 biphasic
      synovial sarcomas expressed glycodelin in the cells exhibiting epithelial or
      glandular differentiation while the sarcomatous spindle cells remained negative.
      Glycodelin was also found in secreted material in the lumina of the gland-like
      structures. In only 1 of the 7 monophasic synovial sarcomas studied, focal
      glycodelin reactivity was seen in some flattened spindle cells. The expression of
      glycodelin in biphasic synovial sarcoma tissue was further verified by the
      demonstration of glycodelin mRNA by reverse transcriptase-polymerase chain
      reaction. Considering the monoclonal origin of synovial sarcomas, our findings
      raise the intriguing possibility that activation of expression of the glycodelin
      gene is involved in the molecular regulation of mesenchyme-to-epithelium
      differentiation.

PMID- 9590123
TI  - Essential fatty acids and breast cancer: a case-control study in Uruguay.
AB  - The relationship between frequency of intake of different types of fat and breast
      cancer was investigated in a case-control study conducted in Montevideo, Uruguay,
      during the time period 1994-1996. Our study comprised 365 cases and 397 controls.
      A moderate and non-significant increase in risk of breast cancer, associated with
      total fat intake, was found. Saturated and monounsaturated fat intake were not
      associated to an increased risk of this malignancy, whereas polyunsaturated fat
      and linoleic acid were associated with a significantly reduced risk (OR 0.26, 95%
      CI 0.13-0.53). On the contrary, both alpha-linolenic acid and cholesterol intakes
      were associated with an increased risk of breast cancer (OR for the upper
      quartile of intake of alpha-linolenic acid 3.79, 95% CI 1.53-9.40). When alpha
      linolenic was examined at different levels of intake, the OR's were significantly
      higher at low levels of linoleic acid intake (OR 7.5, 95% CI 1.9-28.8).

PMID- 9590124
TI  - Mitochondrial DNA sequence variation in human leukemic cells.
AB  - The Long PCR followed by the RFLP technique has been used to search for
      abnormally structured mitochondrial DNA (mtDNA) and specific sequence differences
      implicated in the pathogenesis of acute lymphoblastic leukaemia (ALL). We have
      studied 54 specific sites whose combinations define groups of mtDNA types, in 30
      leukemic patients of French Caucasian origin. Results were compared with those in
      100 French healthy individuals. Nucleotide substitutions have been defined in 11
      patients. This polymorphism is expressed by single base substitution at 6 sites
      which corresponds to 5 morphs, 2 of which were not found in the reference group.
      Combining the 11 observed morphs, we have identified 7 different mtDNA types,
      defined in 30 patients with ALL. Two of the morphs (MspI-2 and AvaII-3) and 3 of
      the types (17-2, 55-2, NewFr150) were not found in the group of healthy
      individuals. We have observed significant statistical changes in type 28-2 in ALL
      patients compared with the controls.

PMID- 9590126
TI  - Growth-inhibitory effects of luteinizing hormone-releasing hormone (LHRH)
      agonists on xenografts of the DU 145 human androgen-independent prostate cancer
      cell line in nude mice.
AB  - Experiments have been performed to clarify whether LHRH agonists might decrease
      growth of hormone-unresponsive prostate cancer in vivo. Male nude mice were
      injected s.c. with the human androgen-independent prostate tumor DU 145 cells;
      osmotic minipumps releasing the LHRH agonist Zoladex (LHRH-A) for 14 days were
      simultaneously implanted under the skin. Treatment with LHRH-A induced a
      significant decrease in tumor growth up to the end of the treatment. In
      subsequent experiment, minipumps releasing LHRH-A were implanted in nude mice
      either 7 or 14 days after cell inoculation. When the treatment was started 7 days
      after inoculation of the cells, tumor growth was significantly decreased up to 28
      days; thereafter, tumor volume remained lower than in controls, although not
      significantly. When LHRH-A was administered beginning 14 days after cell
      inoculation, tumor growth was not significantly affected at any time interval
      considered. LHRH-A did not appear to induce apoptosis in DU 145 cells, at least
      on the basis of the apoptotic index and immunohistochemical staining of the p53
      protein. On the other hand, treatment with LHRH-A was accompanied by a
      significant decrease of the concentration of epidermal growth factor receptors in
      DU 145 prostate cancer specimens. Our results show that the LHRH agonist used
      significantly inhibits the growth of DU 145 androgen-independent prostate tumor
      xenografts in nude mice.

PMID- 9590125
TI  - Therapeutic efficacy and apoptosis and necrosis kinetics of doxorubicin compared
      with cisplatin, combined with whole-body hyperthermia in a rat mammary
      adenocarcinoma.
AB  - We have compared the therapeutic efficacy as well as the kinetics of treatment
      induced apoptosis and necrosis of the maximum tolerated dose (MTD) of doxorubicin
      (DOX) or cisplatin (CDDP) combined with long-duration, low-temperature whole-body
      hyperthermia (LL-WBH, at 40.0 degrees C for 6 hr), with the combination of the
      MTDs of either DOX or CDDP with short-duration, high-temperature WBH (SH-WBH, at
      41.5 degrees C for 2 hr), in a rat mammary adenocarcinoma (MTLn3). The MTD of LL
      WBH + DOX resulted in increased therapeutic efficacy, compared with the MTD of
      DOX alone and SH-WBH + DOX. The MTD of LL-WBH + CDDP, however, did not increase
      therapeutic efficacy, when compared with the MTD of CDDP alone or SH-WBH + CDDP.
      The MTD of LL-WBH + DOX caused a significant delay in the development of
      spontaneous axillary lymph node (ALN) metastasis and tended to cause longer mean
      survival, compared with SH-WBH + DOX. The peak of treatment-induced apoptosis was
      higher for the MTD of DOX + LL-WBH, compared with SH-WBH + DOX, whereas the
      apoptosis peak of the MTD of SH-WBH + CDDP was higher than that of LL-WBH + CDDP.
      The most extensive levels of tumor necrosis appeared to occur earlier with SH-WBH
      alone and the MTD of SH-WBH + DOX or CDDP than with other groups. Our results
      suggest that LL-WBH + DOX may be a promising therapy for breast cancer, and the
      extent of treatment-induced tumor apoptosis appears to correlate with antitumor
      response for MTDs of LL-WBH + DOX and SH-WBH + DOX, but not for the MTDs of CDDP
      with SH-WBH or LL-WBH.

PMID- 9590127
TI  - Sulfated glycoglycerolipid from archaebacterium inhibits eukaryotic DNA
      polymerase alpha, beta and retroviral reverse transcriptase and affects methyl
      methanesulfonate cytotoxicity.
AB  - A sulfated glycoglycerolipid, 1-O-(6'-sulfo-alpha-D-glucopyranosyl)-2,3-di-O
      phytanyl- sn-glycerol (KN-208), a derivative of the polar lipid isolated from an
      archaebacterium, strongly inhibited DNA polymerase (pol) alpha and pol beta in
      vitro among 5 eukaryotic DNA polymerases (alpha, beta, gamma, delta, and
      epsilon). It also inhibited Escherichia coli DNA polymerase I Klenow fragment (E.
      coli pol I) and human immunodeficiency virus reverse transcriptase (HIV RT). The
      mode of inhibition of these polymerases was competitive with the DNA template
      primer and was non-competitive with the substrate dTTP. KN-208 inhibited pol beta
      most strongly, with a Ki value of 0.05 microM, 10-fold lower than that for pol
      alpha (0.5 microM) and 60- or 140-fold lower than that for HIV RT (3 microM) or
      for E. coli pol I (7 microM), respectively. The loss of sulfate on the 6'
      position of glucopyranoside of this compound completely abrogated inhibition.
      However, the hydrophilic part of KN-208, glucose 6-sulfate alone, showed no
      inhibition. Other sulfated compounds containing different hydrophobic structures,
      such as dodecyl sulfate and cholesterol sulfate, exhibited a much weaker
      inhibition. Our results suggest that the whole molecular structure of KN-208 is
      required for inhibition. KN-208 was shown to be modestly cytotoxic for the human
      leukemic cell line K562. Interestingly, a subcytotoxic dose of KN-208 increased
      the sensitivity of the human leukemic cells to an alkylating agent, methyl
      methanesulfonate, while it did not potentiate the effects of ultraviolet light or
      of cisplatin.

PMID- 9590128
TI  - Androgen-independent basal cell re-epithelialization, c-erbB-2 mRNA expression
      and androgen-dependent EGFr mRNA expression in benign prostatic hyperplasia
      explant cultures treated with finasteride.
AB  - We have analyzed the effects of the 5alpha-reductase inhibitor, finasteride
      (MK906), on the mRNA expression of the epidermal growth factor receptor and c
      erbB-2 genes, in benign prostatic hyperplasia explant cultures treated with
      testosterone and with testosterone plus finasteride. A decrease of the epithelial
      cell content and an androgen-independent basal cell re-epithelialization was
      observed during the first 10 days of culture, suggesting a role of basal cells as
      stem cells involved in androgen-independent epithelial regeneration. Using a semi
      quantitative reverse transcription polymerase chain reaction technique, we
      observed a significant decrease in expression of the epidermal growth factor
      receptor in the cultures treated with finasteride whereas no effect of
      finasteride on c-erbB-2 transcription was detected, although the expression of
      both genes was increased by dihydrotestosterone.

PMID- 9590129
TI  - Down-regulation of c-myc and bcl-2 gene expression in PU.1-induced apoptosis in
      murine erythroleukemia cells.
AB  - We found that over-expression of PU.1, a member of the ets family of
      transcription factors, induces apoptotic cell death along with differentiation of
      DMSO stimulation in murine erythroleukemia (MEL) cells. To elucidate the
      molecular mechanisms of apoptosis, cell-cycle distribution and expression of
      several genes encoding apoptosis-promoting and -inhibiting factors were analyzed
      during the process of PU.1-induced apoptosis. FACS analysis revealed that cells
      were accumulated in the G0/G1 phase of the cell cycle before apoptosis.
      Morphological analysis of PI-stained nuclei of the apoptotic cells sorted by a
      FACScan showed 22.6% in G0/G1, 35.8% in S and 8.5% in G2/M phase by fluorescent
      microscopy after cell sorting, suggesting that PU.1-induced apoptosis in MEL
      cells occurs in G0/G1 through S phases. Semi-quantitative RT-PCR revealed that
      expression of c-myc and bcl-2 genes was reduced during the apoptotic process,
      while expression of bax and bcl-X(L) genes was not changed. Expression of the p53
      gene was reduced rather than enhanced, suggesting that PU.1-induced apoptosis in
      MEL cells is p53-independent. Apoptosis was inhibited by adding 30% serum in
      culture, while no reduction of c-myc and bcl-2 gene expression was observed.
      Forced expression of the c-myc, bcl-2 and bcl-X(L) genes protected MEL cells from
      apoptosis. Our results suggest that a reduction of at least 2 important apoptosis
      inhibiting factors, c-Myc and Bcl-2, is involved in PU.1-induced apoptosis in MEL
      cells.

PMID- 9590130
TI  - Antiproliferative activity of interferon alpha and retinoic acid in SiHa
      carcinoma cells: the role of cell adhesion.
AB  - Several lines of evidence have demonstrated that IFNs could be relevant in the
      treatment of certain neoplastic diseases such as carcinomas. In particular, IFN
      alpha, in addition to the anti-proliferative and cytostatic effects, was
      demonstrated to be capable of inducing cell death by apoptosis both in vivo and
      in vitro. Numerous protocols have also been proposed which consider the
      association of IFN-alpha with other drugs. Among these are retinoids, a class of
      compounds capable of inducing inhibition of cell growth and differentiation. We
      address the question here by analyzing the role of cell adhesion in
      susceptibility to IFN-alpha, RA and their combination of a human cell line
      derived from a squamous carcinoma of the cervix, the Bcl-2-negative SiHa cell
      line. In this context, cytoskeleton components and several surface molecules
      playing a role in cell substrate and cell-to-cell relationships have been
      evaluated. We found that RA treatment is capable of improving stress fiber
      formation, decreasing cell detachment and increasing cell-adhesion capability.
      However, no variations in the ability to adhere to specific extracellular-matrix
      molecules were found in RA-treated cells. No quantitative changes were detected
      in integrins involved as receptors for extracellular matrix molecules (VLAI-VLA5)
      or in other cell-adhesion-associated molecules (e.g., CD44). By contrast, 2
      important molecules involved in cell-adhesion processes appeared to be up
      regulated by RA exposure: focal adhesion kinase and E-cadherin, involved in
      adhesion plaque formation and cell-to-cell contacts, respectively. Keeping in
      mind the importance of adhesion properties in the cell-growth pathway, our
      findings could be of interest in the study of carcinoma-cell proliferation and
      metastatic potential.

PMID- 9590131
TI  - Endoglin, a component of the TGF-beta receptor system, is a differentiation
      marker of human choriocarcinoma cells.
AB  - Endoglin is an integral membrane glycoprotein that binds transforming growth
      factor-beta1 (TGF-beta1) with high affinity and it is strongly expressed on
      syncytiotrophoblasts throughout pregnancy. Here, we describe the expression of
      endoglin by the choriocarcinoma cell line JAR as evidenced by flow cytometry,
      immunoprecipitation, Western blot and reverse transcriptase polymerase chain
      reaction analyses. Cross-linking experiments of [125I]-labeled TGF-beta1 to JAR
      cells indicated that endoglin expressed at the surface of these cells binds TGF
      beta. Furthermore, staining of human choriocarcinoma tissue sections with a
      polyclonal antibody to endoglin demonstrated a high expression of endoglin in
      syncytiotrophoblast-like areas, as opposed to a negative staining of
      cytotrophoblast-like cells. This pattern of endoglin expression was confirmed by
      experiments with methotrexate, an inducer of giant, multinucleated, non
      proliferative cells, morphologically indistinguishable from the naturally
      occurring syncytiotrophoblasts. Thus, treatment of the JAR and JEG-3
      choriocarcinoma cell lines with methotrexate led to an increase in endoglin
      expression, as demonstrated by Western and Northern blot analyses. Taken
      together, our results suggest that endoglin, in addition to being involved in
      placental development, may also be a cellular differentiation marker.

PMID- 9590132
TI  - Novel way to increase targeting specificity to a human glioblastoma-associated
      receptor for interleukin 13.
AB  - Human brain cancers (gliomas) overexpress large numbers of a receptor for
      interleukin 13 (IL13), making this receptor an attractive target for anti-glioma
      therapies. We have recently proposed that the glioma-associated IL13 receptor is
      different from the one expressed on some hemopoietic and somatic cells. In an
      attempt to identify an even more glioma-specific target, we have used an
      antagonist of a related cytokine, IL4, which neutralizes the physiological
      effects of both IL13 and IL4 on normal cells. Here we demonstrate that the IL4
      antagonist also counteracts the action of cytotoxins targeted to the IL13
      receptor on normal human cells. Importantly, the IL4 antagonist does not inhibit
      IL13-based cytotoxins on glioma cells at all. Thus, the IL13 receptor on glioma
      cells can be categorized as tumor-specific in the presence of an IL4 antagonist.
      We conclude that IL13 receptor-directed cytotoxins can be delivered to glioma
      cells without being cytotoxic to normal cells.

PMID- 9590133
TI  - Suppression of intracellular resistance factors by adriamycin augments heat
      induced apoptosis via interleukin-1beta-converting enzyme activation in
      pancreatic carcinoma cells.
AB  - Combination of heat and various anticancer drugs can exert a synergistic
      antitumor effect in vitro and in vivo, though the mechanism is not clear. We have
      previously shown that endogenous tumor necrosis factor (enTNF) acts as an
      intracellular resistance factor to inhibit the cytotoxic effect of heat by
      scavenging oxygen-free radicals via the induction of manganous superoxide
      dismutase (MnSOD). Consequently, we examined whether the suppression of these
      resistance factors by combining anticancer drugs and heat causes an augmentation
      of heat-induced cytotoxicity. The human pancreatic carcinoma cell line, PANC-1,
      constitutively expresses appreciable amounts of enTNF and also demonstrates heat
      resistance. After treatment of these cells for 15 hr with adriamycin (ADM), the
      expression of enTNF was decreased by 43%, and MnSOD activity was suppressed by
      55%. The cytotoxic effects of the treatment of PANC-1 cells with ADM followed by
      heat were greater than the sum of those observed with the agents administrated
      individually. Heat-induced apoptosis was also augmented by pretreatment with ADM.
      Furthermore, the interleukin-1beta-converting enzyme inhibitor, Ac-YVAD-CMK,
      reversed the augmented cytotoxicity. Our results indicate that suppression of
      intracellular resistance factors such as enTNF and MnSOD plays an important role
      in apoptosis seen after heat and ADM combined therapy.

PMID- 9590134
TI  - Liver metastasis and adhesion to the sinusoidal endothelium by human colon cancer
      cells is related to mucin carbohydrate chain length.
AB  - Mucin production by human colon cancer cells correlates with liver metastasis in
      animal models, but it is not known which steps in metastasis depend on specific
      alterations in mucin synthesis. Clonal variants of cell line LS174T selected for
      differences in mucin core carbohydrate expression have been further characterized
      biochemically, and tested for their ability to participate in metastasis-related
      events. LS-C mucin contains truncated carbohydrates enriched for sialyl Tn and
      these cells bind to basement membrane matrix to a greater extent than LS-B cells.
      This binding is partially inhibitable by antibody to sialyl Tn. LS-B produces
      more fully glycosylated mucin and preferentially binds to hepatic sinusoidal
      endothelial cells and E-selectin through sialylated peripheral mucin-associated
      carbohydrate structures. Adhesion of LS-B to endothelial cells is inhibited by
      neutralizing antibody to E-selectin, and inhibition of glycosylation or
      desialylation of LS-B mucin abrogates binding to E-selectin in vitro. LS-B cells
      spontaneously metastasized from cecum to liver and colonized the liver of athymic
      mice after splenic-portal injection to a significantly greater extent than LS-C,
      suggesting that expression of peripheral mucin carbohydrate structures is most
      important for metastasis of human colon cancer cells.

PMID- 9590135
TI  - Cooperativity between the polyamine pathway and HER-2neu in transformation of
      human mammary epithelial cells in culture: role of the MAPK pathway.
AB  - Our experiments were designed to test the cooperativity between the polyamine
      pathway and HER-2neu in inducing transformation of human mammary epithelial cells
      in culture. Using the MCF-10A breast epithelial cell line, we observed that
      induction of overexpression of ornithine decarboxylase (ODC) (the first rate
      limiting enzyme in polyamine biosynthesis) markedly potentiated the anchorage
      independent growth stimulating effect of the beta2 isoform of neu differentiating
      factor (NDF) known to activate HER-2neu in MCF-10A cells. ODC overexpression, on
      the other hand, did not enhance growth in liquid culture, thus pointing to a
      specific effect on transformation rather than proliferation. ODC-overexpressing
      MCF-10A cells exhibited increased MAPK phosphorylation in response to
      administration of NDF and/or epidermal growth factor (EGF). In contrast, the
      phosphorylation of the members of the stress-activated protein kinase cascade p38
      and SEK were not affected by ODC overexpression. Of note, in the absence of EGF
      and NDF, ODC overexpression failed to induce both clonogenicity and MAPK
      activation. These results suggest that increased polyamine biosynthetic activity
      critically interacts with HER-2neu in promoting human mammary cell transformation
      in culture and that the MAPK cascade is an important mediator of this
      interaction. If confirmed in future in vivo studies, our results may identify
      important new targets for the chemoprevention of human breast cancer.

PMID- 9590136
TI  - Human chorionic gonadotropin (hCG) inhibits cisplatin-induced apoptosis in
      ovarian cancer cells: possible role of up-regulation of insulin-like growth
      factor-1 by hCG.
AB  - Gonadotropins have been suggested to play a role in the development or
      progression of ovarian cancer, and we have previously reported the expression of
      luteinizing hormone/ human chorionic gonadotropin (LH/hCG) receptor in 40% of
      epithelial ovarian carcinomas. To examine the biological effect of LH/hCG on
      ovarian cancer cells, apoptosis induced by cisplatin with or without hCG
      treatment was investigated in 2 ovarian cancer cell lines, OVCAR-3 and SK-OV-3.
      Stimulation of cell proliferation by hCG was also studied. In addition, to
      analyze further the mechanism of hCG signaling involved in apoptosis-inhibition,
      we examined the expression of LH/hCG receptors and the regulation by hCG for
      apoptosis-inhibitory pathways, such as the bcl-2/bax system and the insulin-like
      growth factor-1 (IGF-1)/IGF-1 receptor (IGFR) system. hCG did not increase cell
      proliferation in either cell line. However, hCG treatment suppressed cisplatin
      induced apoptosis by 58% in the OVCAR-3 cells, as shown by immunofluorescent
      staining and quantitation of DNA fragmentation. LH/hCG receptor mRNA was
      expressed only in OVCAR-3, and no apoptosis-inhibitory effect of hCG was observed
      in the SK-OV-3 cells that did not express the receptor. In the OVCAR-3 cells, hCG
      significantly increased mRNA expression of IGF-1, but did not change mRNA levels
      of bcl-2/bax. Our findings suggest that LH/hCG influences the chemosensitivity of
      ovarian cancer cells through an apoptosis-inhibitory signal possibly via up
      regulation of IGF-1 expression.

PMID- 9590137
TI  - Thymic anti-tumor effectors in mice cured of lymphoma by cyclophosphamide plus
      TNF-alpha therapy: phenotypic and functional characterization up to 20 months
      after initial tumor inoculation.
AB  - As reported previously, cyclophosphamide plus tumor necrosis factor-alpha
      treatment of C57BL/6 mice bearing advanced EL4 lymphoma induced approx. 60% long
      term (i.e., >60 days) survivors. These mice developed protective immunity, as
      evidenced by 1) rejection (100% survival) of EL4 tumor re-implanted on day 60
      (day 0 = initial tumor implantation); and 2) development of significant levels of
      specific EL4 tumor cell killing activity by both splenocytes and thymocytes.
      Using this model, age-related changes in functionally and phenotypically
      definable thymocyte subsets were assessed. In thymocytes from 90 to 308 day
      survivors, specific immune memory was long term; both CD4+ and CD8+ cells were
      required for the ex vivo stimulation of lytic activity, but the specific anti-EL4
      cytotoxic effector was CD4-CD8+. On day 520, the surviving mice were randomized
      into 2 groups. One group received a second re-challenge with EL4 tumor cells and
      all survived. The other group was sacrificed on day 520. Their thymocytes,
      exposed to X-irradiated EL4, developed anti-EL4 lytic activity and, in comparison
      with thymocytes of young and age-matched control mice, were markedly enriched in
      CD4-CD8+CD44+ cells. On day 625, thymocytes from the survivors of the day 520 re
      challenge were evaluated and were found to have developed specific anti-EL4 lytic
      activity. Phenotypically, they had returned toward the pattern seen in age
      matched control mice although CD4-CD8+CD44+ cells remained increased. These mice
      were > or = 2 years old, the median life span of C57BL/6 mice. Thus, mice cured
      of tumor by an immuno-modulating regimen rejected re-implanted primary tumor and
      maintained specific thymic anti-tumor immune memory for life.

PMID- 9590138
TI  - Epstein-Barr-virus-infected human T-cell line with a unique pattern of viral-gene
      expression.
AB  - Epstein-Barr-virus(EBV)-gene expression was analyzed in clonal sub-lines of the
      human T-cell line MT-2 that are persistently infected by the virus with a
      positive selection marker. Immunoblot analyses showed the expression of EBV
      proteins associated with the latent viral cycle, including the EBV nuclear
      antigen 1 (EBNA1) and the latent membrane protein 1 (LMP1), whereas EBNA2 was not
      detected. RT-PCR further demonstrated the expression of LMP2A, EBV-encoded small
      RNA 1 (EBER1), and complementary-strand transcripts from the BamHI-A fragment.
      EBNA2 mRNA was detected at a very low level. In addition to these latent viral
      functions, the BZLF1 protein, a transcription factor that activates a cascade of
      replicative-gene expression in EBV-infected B cells, was detected in these MT-2
      clones by immunoblot analysis and immuno-enzymatic staining. Moreover, mRNA from
      other genes of the early virus-replicative cycle, such as BRLF1, BSMLF1, and
      BALF2, as well as BZLF1 was detected by Northern-blot analysis. Since sub-lines
      of the human B-cell lines BJAB and Louckes infected with similar recombinant EBV
      did not express these early genes, these data suggest that MT-2 cells are
      relatively permissive for expression of early EBV-replicative functions.

PMID- 9590139
TI  - Potent antitumor activity of the acyclic nucleoside phosphonate 9-(2
      phosphonylmethoxyethyl)adenine in choriocarcinoma-bearing rats.
AB  - The acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is
      a potent and selective antiretroviral agent which is currently evaluated in its
      oral prodrug form, bis(POM)PMEA (adefovir dipivoxil), in phase II and III
      clinical trials in human hepatitis B virus (HBV)- and human immunodeficiency
      virus (HIV)-infected individuals, respectively. We have now found that PMEA is
      also a potent inhibitor of growth of the highly aggressive choriocarcinoma tumor
      arising from rat choriocarcinoma RCHO cells grafted under the kidney capsule of
      syngeneic WKA/H rats. In untreated rats, massive invasive RCHO tumors, covering
      the whole surface of the kidney and resulting in a marked enlargement of the
      kidney, were observed at day 10 after tumor cell grafting. Daily treatment with
      PMEA at 25 mg/kg/day afforded a marked reduction in tumor size (i.e., smaller
      tumors and slight, if any, enlargement of the kidney). Increasing the PMEA dose
      to 50, 100 or 250 mg/kglday resulted in a gradual increase of the antitumor
      effect of the compound. At the highest dose tested, i.e., 250 mg/kg/day, PMEA
      completely suppressed tumor growth. The antitumor activity of PMEA persisted for
      at least 10 days after termination of drug treatment. In addition, delayed
      treatment with PMEA at a dose of 200 mg/kg/day, started at a time point where
      choriocarcinoma tumors had already developed, stopped further growth and even
      induced regression of the tumors. PMPA, a closely related structural analogue of
      PMEA, failed to inhibit choriocarcinoma tumor growth. This observation points to
      the specificity of PMEA as an antitumor agent. In view of our findings, the
      therapeutic potential of PMEA for the treatment of neoplastic diseases appears to
      merit further investigation.

PMID- 9590140
TI  - Effects of the farnesyltransferase inhibitor UCF-1C/manumycin on growth and p21
      ras post-translational processing in NIH3T3 cells.
AB  - Examination of the effect of the farnesylprotein transferase (FPTase) inhibitor
      UCF1-C/manumycin on NIH3T3 cells transfected with a normal N-ras gene and
      expressing high levels of the corresponding p21-ras protein showed that 10 microm
      UCF1-C immediately and reversibly inhibited growth in these cells, without
      modifying cell-death rate, thus acting as a cytostatic. There was also a 98%
      reduction of p21-ras neofarnesylation and a 3-fold decrease in total content in
      p21-ras products, yet without gross modification of the relative content in the
      post-translational products and without accumulation of the native protein to
      detectable levels. UCF1-C likewise reversibly inhibited growth in parental NIH3T3
      cells, as well as in sub-strains expressing a transfected normal or mutated H-ras
      gene. Together with the fact that the well-developed network of actin stress
      fibers present in the NIH3T3 (N-ras) cells was not affected by the FPTase
      inhibitor, these data indicate that its growth-inhibitory effect is not
      necessarily in direct relation with that exerted on p21-ras processing.
      Alternatively, it might be causally related to the decreased prenylation of other
      cellular proteins, perhaps included among the 13 proteins, unrelated to p21-ras,
      of which the farnesylation was also reduced under UCF1-C treatment. Some cells
      transformed by a ras or non-ras oncogene might exhibit higher susceptibility
      towards FPTase inhibitors than normal cells, but this might then be attributable
      to differences in the pattern of expression and/or in the functional importance
      of non-ras farnesylated proteins.

PMID- 9590141
TI  - Treatment of multifocal lymphoma of bone with intensified ProMACE-CytaBOM
      chemotherapy and involved field radiotherapy.
AB  - Primary bone involvement is an unusual extranodal presentation of non-Hodgkin
      lymphoma (NHL). The optimal treatment for this entity has not been determined.
      While solitary bone lymphomas can be eradicated with local radiation in 50% of
      patients, distant relapses occur frequently, and the treatment of patients with
      multifocal osseous disease, or those presenting with associated soft tissue
      invasion or adenopathy is even less satisfactory. Over a 4-year period, nine
      patients with multifocal bone lymphoma were treated with intensified versions of
      the ProMACE-CytaBOM regimen and involved-field radiation. Seven patients had
      diffuse large cell histology and two patients had diffuse mixed type. Seven
      patients survived event-free at a median follow-up of 2.3 years (range .5-3.5).
      In most survivors, there was little or no change in the abnormal radiographic
      bone findings despite the clinical response to therapy. In one patient, magnetic
      resonance imaging (MRI) established that bone infarction rather than relapse of
      lymphoma was the cause of a new lytic bone lesion that developed during
      treatment.

PMID- 9590142
TI  - Neonatal neutrophil inflammatory responses: parallel studies of light scattering,
      cell polarization, chemotaxis, superoxide release, and bactericidal activity.
AB  - Neutrophil dysfunction among newborn infants, especially those born prematurely,
      is well recognized, but the mechanism responsible for this phenomenon is yet to
      be clarified. In this study, we evaluated the stimulus response coupling in
      neutrophils from 90 healthy newborns and 96 healthy adults in an effort to
      establish whether defective neonatal neutrophil function is a result of impaired
      signal perception or immature responsiveness. Measurement of rapid- and slow
      light scattering responses (LSR) to 1 microM FMLP stimulation revealed that
      neonatal neutrophils have about one-half the corresponding responsiveness of
      adult cells (rapid-LSR: 6.1 +/- 3.1 arbitrary light intensity units vs. 12.0 +/-
      2.8, P < .001; and slow-LSR: 5.0 +/- 2.5 vs. 9.1 +/- 2.0; P < .001). The same
      markedly reduced activity was observed in newborn neutrophil chemotaxis and
      bactericidal activity in comparison with adult cells. Nevertheless, low FMLP
      concentrations (less than 1 nM) induced no difference in cell polarization
      between newborn and adult neutrophils, yet at higher FMLP concentrations, the
      newborn revealed significantly reduced cell polarization. Our data suggest that
      newborn infants bear a fully functional FMLP signal perception but lack the full
      capacity of inflammatory responsiveness.

PMID- 9590143
TI  - Factors affecting the rate of iron mobilization during venesection therapy for
      genetic hemochromatosis.
AB  - Although progressive iron accumulation is a characteristic feature of genetic
      hemochromatosis, the factors affecting the rate of iron mobilization by
      venesection have not been established. Venesection records were analyzed in 77
      hemochromatosis homozygotes to study the factors affecting the rate of iron
      mobilization by venesection. The rate of iron mobilization was the iron removed
      divided by the time required to deplete iron stores (serum ferritin < 50
      microg/L). Mean duration of venesection therapy was 1.4 years (range 0.44-3.6
      years). All patients completed the therapy and there were no significant adverse
      effects. Rate of iron mobilization was higher in cirrhotics compared to non
      cirrhotic patients (P = 0.04). Iron mobilization was inversely related to
      intestinal radioiron absorption (r = -0.45, P = .01). There was no significant
      relationship between iron mobilization and patient age, gender, serum ferritin,
      and hepatic iron concentration. Iron mobilization is increased in cirrhotics and
      patients with lower intestinal iron absorption. Venesection therapy is safe and
      well tolerated in all age groups.

PMID- 9590144
TI  - High-dose cytarabine-containing chemotherapy with or without granulocyte colony
      stimulating factor for children with acute leukemia.
AB  - We sought to determine the role of granulocyte colony-stimulating factor (G-CSF)
      as an adjunct therapy in high-dose cytarabine-containing chemotherapy (HD C/T)
      for children with acute leukemia. Seventeen patients, aged 9 months to 18 years
      old, 8 ALL and 9 AML, were treated with cytarabine (Ara-C) 1 g/m2 q12h for 8
      doses with mitoxantrone, idarubicin, VP-16, or asparaginase. A total of 71
      courses of HD C/T was given. G-CSF was not used in 14 courses (Group A).
      Prophylactic G-CSF was given in 57 courses (Group B) as 200 microg/m2/d SC
      started one day after the completion of HD C/T and continued until the neutrophil
      recovery was maintained. The incidences of sepsis per course in Group A and Group
      B were 35.7% (5/14) and 40.4% (23/57), respectively. While 2 patients in Group A
      died of sepsis or pneumonia, none in Group B died. The mortality and delay in
      chemotherapy were fewer in Group B (P = 0.037 and 0.0006, respectively, Fisher
      exact test). There was a shorter average number of days of neutrophil <500/cumm,
      antibiotic usage, fever, and hospital stay in Group B (11, 8, 5, 17 days in Group
      B vs. 21, 17, 10, 37 days in Group A; P = 0.0001, log-rank test; 0.0006, 0.0023,
      0.0001, Wilcoxon rank sum test, respectively). The incidence of neutropenic fever
      was lower in Group B, but the difference did not reach statistical significance
      (P = 0.06, Fisher exact test). We conclude that G-CSF as an adjunct therapy in HD
      C/T is effective in reducing mortality, days of neutropenia, antibiotic usage,
      fever, hospital stay, and frequency of delay in chemotherapy. The efficacy of
      this treatment approach requires further testing in a randomized, controlled
      trial.

PMID- 9590145
TI  - Simultaneous binding of heparin and platelet factor-4 to platelets: further
      insights into the mechanism of heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is mediated by antibody against complexes
      of platelet factor-4 (PF4) and heparin. Although it has been assumed that these
      complexes bind to platelets and provide a target for the antibody, this has never
      been demonstrated. Furthermore, there is evidence suggesting that heparin-PF4
      complexes do not bind to platelets. We have analyzed the effect of each ligand on
      the platelet binding of the other. We particularly focused on the result when
      heparin and PF4 are in equimolar concentration because we had previously shown
      that this was the condition under which HIT-IgG increased on the platelet
      surface. We found that when the molar concentration of PF4 approximates or
      exceeds that of heparin, the ligands bind simultaneously to the cells and HIT-IgG
      binds also. However, when heparin is in molar excess, both PF4 binding and HIT
      IgG binding are diminished. Our data are consistent with the hypothesis that
      heparin-PF4 complexes bind via their heparin component to heparin binding sites
      on the platelet membrane rather than by their PF4 component to PF4 sites. The
      conditions promoting the binding of the complexes also lead to binding of HIT
      IgG.

PMID- 9590146
TI  - Granulocyte colony-stimulating factor and its receptor in acute promyelocytic
      leukemia.
AB  - Expression of granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) and
      in vitro proliferative response to G-CSF were investigated by quantitative
      immunofluorescence and [3H] thymidine uptake, respectively, in a series of acute
      myeloid leukemias (AML). The results indicated that G-CSFR was detected at high
      levels in acute promyelocytic leukemia (APL) cells, in comparison with other
      types of AML. Moreover, APL cells were also seen to predominantly proliferate in
      response to G-CSF. Based on these observations, we administered recombinant human
      G-CSF to a patient with APL in the third relapse that was resistant to both
      cytotoxic agents and all trans retinoic acid, in an attempt to sensitize the
      leukemic cells to cell-cycle-dependent agents. Complete remission was achieved.
      The finding that APL cells are exquisitely responsive to G-CSF supports the view
      that G-CSF is useful for augmentation of their vulnerability to cell-cycle
      specific agents.

PMID- 9590147
TI  - Two distinct truncated variants of ankyrin associated with hereditary
      spherocytosis.
AB  - We present two distinct truncated variants of ankyrin associated with mild to
      moderate hereditary spherocytosis. Ankyrin Saint-Etienne 1 was manifested by an
      additional band located between bands 2.1 and 2.2. It was associated with a
      nonsense mutation in exon 39: TGG-->TGA; W1721X. Ankyrin Saint-Etienne 2 appeared
      as two faint bands underlining bands 2.1 and 2.2. It was associated with a
      nonsense mutation in exon 41: CGA-->TGA; R1833X. Overall ankyrin was diminished
      in splenectomized patients. Messenger RNAs Saint-Etienne 1 and 2 amounted to 20
      and 37% of the total ankyrin mRNA, respectively. Ankyrin molecules truncated in
      their C-terminal region retain some ability to bind to the membrane whereas the
      bulk of nonsense mutations, located in more upstream regions, result in the mere
      disappearance of one haploid set of ankyrin. In the present cases, it was not
      possible to apportion the roles of ankyrin reduction and truncation in the
      pathogenesis of hereditary spherocytosis.

PMID- 9590148
TI  - Expressions of p53 and PCNA do not correlate with the international index or
      early response to chemotherapy in non-Hodgkin's lymphoma.
AB  - The expression of p53 and PCNA on deparaffinized sections of tumor was assessed
      in relation to the International Index and response to chemotherapy. Thirty-five
      non-Hodgkin's lymphoma (NHL) patients were divided into three groups: aggressive
      NHL, mantle cell lymphoma (MCL), and low-grade NHL. None of the expressions
      correlated with the International Index or early response to chemotherapy in any
      group. In low-grade NHL, none of the patients expressed p53. Only one of three
      patients with overexpression of p53 showed conformational change and alteration
      of sequence in exon 7 by PCR-SSCP and DNA sequencing. The results showed that p53
      and PCNA staining were not useful for predicting early response to chemotherapy,
      and that their expressions had no correlation with the International Index.

PMID- 9590149
TI  - Haplotype analysis and Agamma gene polymorphism associated with the Brazilian
      type of hereditary persistence of fetal hemoglobin.
AB  - We have identified three unrelated individuals and three members of a family with
      the non-deletion form of Agamma-hereditary persistence of fetal hemoglobin
      (HPFH). Molecular analysis showed that each individual is a heterozygote for a
      previously described -195 Agamma (C-->G) mutation. The beta-globin gene cluster
      was studied using the polymerase chain reaction and related techniques.
      Haplotyping using nine restriction sites identified two closely related
      chromosomes with the -195Agamma mutation, differing only in a single site 3' to
      the beta-globin gene. Further analysis of beta-globin framework indicated that
      the HPFH allele segregates with haplotype V, according to Orkin's classification.
      The second haplotype probably originated by a point mutation or DNA rearrangement
      of a pre-existing -195Agamma chromosome. We also determined the sequences from 
      622 to +55 bp upstream to the Agamma gene and part of the Agamma IVS-2. We found
      four polymorphisms associated to the -195Agamma promoter region. All -195Agamma
      chromosomes had a G at positions -588 and +25 relative to the Agamma gene. One
      individual was also homozygous for polymorphisms at -398 (G-->A), and another at 
      369 (C-->G). Cloning and sequencing of the polymorphic patterns of the 3' region
      of Agamma IVS-2 showed that the mutated allele is linked to beta-globin
      chromosome B. Some correlations between chromosome characteristics and Agamma
      point mutations were also observed.

PMID- 9590150
TI  - High prevalence of thrombocytopenia in SLE patients with a high level of
      anticardiolipin antibodies combined with lupus anticoagulant.
AB  - The relationship between thrombocytopenia and the level of anticardiolipin
      antibodies (aCL) and/or the existence of lupus anticoagulant (LA) ware studied in
      146 patients with systemic lupus erythematosus (SLE). These patients were divided
      into six groups: A, those LA positive with a high level of aCL (>10 U/ml) (10
      cases); B, those LA positive with a low level of aCL (3-10 U/ml) (15 cases); C,
      those LA positive but aCL negative (<3 U/ml) (12 cases); D, LA negatives with a
      high level of aCL (12 cases); E, LA negatives with a low level of aCL (16 cases);
      and F, aCL and LA double negatives (81 cases). The prevalence of thrombocytopenia
      (platelet count < or = 100 x 10(9)L) was by far the highest in group A (9/10
      cases, 90.0%, P < 0.005, Fisher's exact probability test) as compared with group
      B (4/15 cases, 26.7%), group C (4/12 cases, 33.3%), group D (1/12 cases, 8.3%),
      group E (4/16 cases, 25.5%), and group F (9/81 cases, 11.1%). When the
      relationship between moderate thrombocytopenia and arterial or venous thrombosis
      was studied in these patients with SLE, thrombocytopenia was detected in 10
      (83.3%, P < 0.005, Fisher's exact probability test) of 12 patients with arterial
      thrombosis; however, it was present in only 4 (23.5%) of 17 patients with venous
      thrombosis and in 14 (12.3%) of 114 patients without thrombosis. These findings
      suggest that a high aCL activity combined with LA positively reflects a high risk
      for both thrombocytopenia and arterial thrombosis.

PMID- 9590151
TI  - New concepts in assessing sickle cell disease severity.
AB  - Vasoocclusion leads to pain, chronic organ damage, and a decreased life
      expectancy in patients with sickle cell disease. Therapeutic options for sickle
      cell disease have usually been evaluated according to their capacity for reducing
      the frequency of vasoocclusive crises requiring clinical attention. However, the
      frequency of vasoocclusive crises is not representative for the rate of
      accumulating organ damage in most sickle cell patients. This implies that the
      frequency of vasoocclusive crises needn't correlate with disease severity and,
      although being of importance, cannot solely serve as a parameter of treatment
      efficacy. Therefore, additional new objective parameters are needed to
      effectively study the vasoocclusive process in sickle cell disease. Several
      studies show that intricate adhesive interactions between (red) blood cells,
      plasma components, and endothelium play a crucial role in the pathophysiology of
      sickle cell vasoocclusion, offering new potential parameters to effectively
      assess disease severity as well as new therapeutical targets in the near future.
      Whether these adhesive mechanisms involve the causes or the effects of
      vasoocclusion will be determined if their inhibition, by interventive measures,
      results in therapeutic benefits.

PMID- 9590152
TI  - Juvenile myelomonocytic leukemia (JMML) with the hematologic phenotype of severe
      beta thalassemia.
AB  - A 3-year-old Filipino-American child with recurrent fever, splenomegaly, anemia,
      and thrombocytopenia, was found to have a hemoglobin F level of 76.9%. His
      reticulocyte count was elevated (4.3%), and erythroblasts were present in his
      peripheral blood. The child's erythrocytes were microcytic (MCV 66.9 fl) but his
      serum ferritin level was normal. His bone marrow at initial presentation
      demonstrated normal cellularity without an increase in blast cells. The disease
      progressed with worsening anemia, leukocytosis, and thrombocytopenia, with
      increased blasts in his marrow and the appearance of a mediastinal mass. His
      liver, spleen, and lymph nodes were found to be infiltrated with myeloblasts,
      supporting a diagnosis of juvenile myelomonocytic leukemia (JMML). Analysis of
      the child's Hb F showed a Ggamma/Agamma ratio of 2.2, which was within the
      characteristic range for JMML. A globin synthesis study using blood reticulocytes
      showed an alpha/non-alpha globin synthesis ratio of 2.24, typical of severe
      homozygous beta thalassemia. Southern blot analysis of blood-leukocyte DNA from
      the patient and his parents demonstrated no apparent abnormality in the beta
      globin gene promoter or coding regions. The elevated level of Hb F in this child
      with JMML appeared to be part of an acquired Cooley's anemia-like hematologic
      phenotype.

PMID- 9590153
TI  - Hemophilia B in a female carrier due to skewed inactivation of the normal X
      chromosome.
AB  - A novel missense mutation (codon 351, GCT (Ala) --> CCT (Pro)) of the FIX gene
      was characterised in a young female with mild hemophilia B. She is heterozygous
      for the FIX mutation inherited from her carrier mother. Analysis of the methyl
      sensitive Hpa II sites at the 5' end of the hypoxanthine
      phosphoribosyltransferase gene showed that skewed inactivation of the X
      chromosome carrying her normal FIX gene accounted for the hemophilia phenotype.

PMID- 9590154
TI  - Primary plasmacytoma at the site of exit wounds after electrical injury.
AB  - We report a case of primary plasmacytoma occurring 12 years after electrical
      injury. Roentgenograms showed multiple well-circumscribed lytic lesions involving
      both the right and left tibial diaphyseal regions. Bone biopsy from the left
      tibial region showed sheets of monoclonal myeloma cells. No evidence of multiple
      myeloma was found. The patient was treated with local radiation to both tibias
      and had no evidence of recurrence 6 years later. In conclusion, we report the
      first case of primary plasmacytoma of both tibias that occurred after electrical
      injury 12 years before.

PMID- 9590155
TI  - Cutaneous sarcoidosis in a patient with Philadelphia-positive chronic myelogenous
      leukemia treated with interferon-alpha.
AB  - A patient with Philadelphia-positive (Ph+) chronic myelogenous leukemia (CML) was
      diagnosed with cutaneous sarcoidosis after treatment with interferon-alpha (IFN
      alpha). Following IFN-alpha dose reduction, the skin lesions disappeared. Few
      cases of sarcoidosis associated with IFN treatment have been reported, and only
      in one patient with pre-existing CML. Our patient was unique in that (1) the
      sarcoidosis was induced by the IFN-alpha treatment alone, (2) it developed de
      novo, and (3) it was confined to the skin.

PMID- 9590156
TI  - Early cutaneous lesions secondary to hydroxyurea therapy.
AB  - Hydroxyurea is a usually well-tolerated cytostatic agent, but its side effects
      include cutaneous lesions that appear after several years of maintenance therapy
      with hydroxyurea. The reported incidence of such adverse reactions varies from 10
      to 35%; in our Center it is 2%. We describe a patient with essential
      thrombocythemia who presented with ulcers of the hands only 15 days after
      hydroxyurea treatment.

PMID- 9590157
TI  - Transfusion-associated graft-versus-host disease in immunocompetent patient:
      early diagnosis and therapy.
AB  - We report a case of transfusion-associated graft-versus-host disease in a
      previously healthy, 68-year-old Japanese man following an emergency surgery for
      an acute aortic dissection. We confirmed the chimerism of lymphocytes and the
      effect of drug therapy using DNA polymorphism analysis. This method is a
      sensitive, convenient, and rapid method that it is also useful for the evaluation
      of therapy. And the combination therapy with methylprednisolone, cyclosporine,
      and 15-deoxyspergualin may be effective in treating transfusion-associated GVHD.

PMID- 9590159
TI  - Married couple both with myeloproliferative disorder and chromosome 3
      abnormality.

PMID- 9590158
TI  - DAB389IL2 diphtheria fusion toxin produces clinical responses in tumor stage
      cutaneous T cell lymphoma.
AB  - Four patients with late stage cutaneous T cell lymphoma (IB-IVA) who had failed
      at least two previous therapies were treated with DAB389IL2 at 9 or 18 microg/kg
      as 15-min intravenous infusions daily for 5 days every 3 weeks for eight cycles.
      Mild vascular leak syndrome (VLS) with transient edema, hypoalbuminemia, weight
      gain, and myalgias was observed in two of the patients lasting 7-10 days and only
      occurring on the first cycle. One stage IB patient had a pathologic complete
      remission (CR) lasting 11+ months from treatment initiation, one stage IIB
      patient had a complete clinical remission (CCR) lasting >6 months with complete
      clearing of a large tumor lasting >18 months, and one stage IIB and the one stage
      IVA patient had partial remissions (80-99% reduction in tumor masses) lasting 5
      months. While IL2 receptor (IL2R) was expressed on 20-50% of tumor cells prior to
      therapy, recurrent tumor was IL2R negative in three of the patients. DAB389IL2 at
      tolerable doses decreased tumor burden in each of these four standard treatment
      refractory CTCL patients and may offer an important alternative to standard
      palliative chemotherapy regimens.

PMID- 9590160
TI  - The mystique of epigenetics.

PMID- 9590161
TI  - RNA and the epigenetic regulation of X chromosome inactivation.

PMID- 9590162
TI  - Imprinting and the initiation of gene silencing in the germ line.

PMID- 9590163
TI  - Centromeric chromatin and epigenetic effects in kinetochore assembly.

PMID- 9590164
TI  - Centromeres take flight: alpha satellite and the quest for the human centromere.

PMID- 9590165
TI  - Beyond the nucleosome: epigenetic aspects of position-effect variegation in
      Drosophila.

PMID- 9590166
TI  - Yeast heterochromatin: regulation of its assembly and inheritance by histones.

PMID- 9590167
TI  - Trans-sensing effects: the ups and downs of being together.

PMID- 9590168
TI  - Polycombing the genome: PcG, trxG, and chromatin silencing.

PMID- 9590169
TI  - Prion protein biology.

PMID- 9590170
TI  - Zip2, a meiosis-specific protein required for the initiation of chromosome
      synapsis.
AB  - We describe the identification and characterization of the Saccharomyces
      cerevisiae ZIP2 gene, which encodes a novel meiosis-specific protein essential
      for synaptonemal complex formation. In the zip2 mutant, chromosomes are
      homologously paired but not synapsed. The Zip2 protein localizes to discrete foci
      on meiotic chromosomes; these foci correspond to sites of convergence between
      paired homologs that are believed to be sites of synapsis initiation.
      Localization of Zip2p requires the initiation of meiotic recombination. In a
      mutant defective in double-strand break repair, Zip2p colocalizes with proteins
      involved in double-strand break formation and processing. We propose that Zip2p
      promotes the initiation of chromosome synapsis and that localization of Zip2p to
      sites of interhomolog recombination ensures synapsis between homologous
      chromosomes.

PMID- 9590171
TI  - Gene dosage-dependent embryonic development and proliferation defects in mice
      lacking the transcriptional integrator p300.
AB  - The transcriptional coactivator and integrator p300 and its closely related
      family member CBP mediate multiple, signal-dependent transcriptional events. We
      have generated mice lacking a functional p300 gene. Animals nullizygous for p300
      died between days 9 and 11.5 of gestation, exhibiting defects in neurulation,
      cell proliferation, and heart development. Cells derived from p300-deficient
      embryos displayed specific transcriptional defects and proliferated poorly.
      Surprisingly, p300 heterozygotes also manifested considerable embryonic
      lethality. Moreover, double heterozygosity for p300 and cbp was invariably
      associated with embryonic death. Thus, mouse development is exquisitely sensitive
      to the overall gene dosage of p300 and cbp. Our results provide genetic evidence
      that a coactivator endowed with histone acetyltransferase activity is essential
      for mammalian cell proliferation and development.

PMID- 9590172
TI  - Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the
      Jaks in cytokine-induced biologic responses.
AB  - Herein we report the generation of mice lacking the ubiquitously expressed Janus
      kinase, Jak1. Jak1-/- mice are runted at birth, fail to nurse, and die
      perinatally. Although Jak1-/- cells are responsive to many cytokines, they fail
      to manifest biologic responses to cytokines that bind to three distinct families
      of cytokine receptors. These include all class II cytokine receptors, cytokine
      receptors that utilize the gamma(c) subunit for signaling, and the family of
      cytokine receptors that depend on the gp130 subunit for signaling. Our results
      thus demonstrate that Jak1 plays an essential and nonredundant role in promoting
      biologic responses induced by a select subset of cytokine receptors, including
      those in which Jak utilization was thought to be nonspecific.

PMID- 9590173
TI  - Jak2 is essential for signaling through a variety of cytokine receptors.
AB  - A variety of cytokines activate receptor-associated members of the Janus family
      of protein tyrosine kinases (Jaks). To assess the role of Jak2, we have derived
      Jak2-deficient mice. The mutation causes an embryonic lethality due to the
      absence of definitive erythropoiesis. Fetal liver myeloid progenitors, although
      present based on the expression of lineage specific markers, fail to respond to
      erythropoietin, thrombopoietin, interleukin-3 (IL-3), or granulocyte/macrophage
      colony-stimulating factor. In contrast, the response to granulocyte specific
      colony-stimulating factor is unaffected. Jak2-deficient fibroblasts failed to
      respond to interferon gamma (IFNgamma), although the responses to IFNalpha/beta
      and IL-6 were unaffected. Lastly, reconstitution experiments demonstrate that
      Jak2 is not required for the generation of lymphoid progenitors, their
      amplification, or functional differentiation. Therefore, Jak2 plays a critical,
      nonredundant role in the function of a specific group of cytokines receptors.

PMID- 9590174
TI  - Jak2 deficiency defines an essential developmental checkpoint in definitive
      hematopoiesis.
AB  - Janus kinases (Jaks) play an important role in signal transduction via cytokine
      and growth factor receptors. A targeted inactivation of Jak2 was performed. Jak2
      /- embryos are anemic and die around day 12.5 postcoitum. Primitive erythrocytes
      are found, but definitive erythropoiesis is absent. Compared to erythropoietin
      receptor-deficient mice, the phenotype of Jak2 deficiency is more severe. Fetal
      liver BFU-E and CFU-E colonies are completely absent. However, multilineage
      hematopoietic stem cells (CD34low, c-kit(pos)) can be found, and B lymphopoiesis
      appears intact. In contrast to IFNalpha stimulation, Jak2-/- cells do not respond
      to IFNgamma. Jak2-/- embryonic stem cells are competent for LIF signaling. The
      data provided demonstrate that Jak2 has pivotal functions for signal transduction
      of a set of cytokine receptors required in definitive erythropoiesis.

PMID- 9590176
TI  - A function for the AP3 coat complex in synaptic vesicle formation from endosomes.
AB  - Synaptic vesicles can be coated in vitro in a reaction that is ARF-, ATP-, and
      temperature-dependent and requires synaptic vesicle membrane proteins. The coat
      is largely made up of the heterotetrameric complex, adaptor protein 3, recently
      implicated in Golgi-to-vacuole traffic in yeast. Depletion of AP3 from brain
      cytosol inhibits small vesicle formation from PC12 endosomes in vitro. Budding
      from washed membranes can be reconstituted with purified AP3 and recombinant
      ARF1. We conclude that AP3 coating is involved in at least one pathway of small
      vesicle formation from endosomes.

PMID- 9590175
TI  - MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis
      of hypertrophic chondrocytes.
AB  - Homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an
      abnormal pattern of skeletal growth plate vascularization and ossification.
      Although hypertrophic chondrocytes develop normally, apoptosis, vascularization,
      and ossification are delayed, resulting in progressive lengthening of the growth
      plate to about eight times normal. After 3 weeks postnatal, aberrant apoptosis,
      vascularization, and ossification compensate to remodel the enlarged growth plate
      and ultimately produce an axial skeleton of normal appearance. Transplantation of
      wild-type bone marrow cells rescues vascularization and ossification in
      gelatinase B-null growth plates, indicating that these processes are mediated by
      gelatinase B-expressing cells of bone marrow origin, designated chondroclasts.
      Growth plates from gelatinase B-null mice in culture show a delayed release of an
      angiogenic activator, establishing a role for this proteinase in controlling
      angiogenesis.

PMID- 9590177
TI  - TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking.
AB  - Mannose 6-phosphate receptors (MPRs) transport newly synthesized lysosomal
      hydrolases from the Golgi to prelysosomes and then return to the Golgi for
      another round of transport. We have identified a 47 kDa protein (TIP47) that
      binds selectively to the cytoplasmic domains of cation-independent and cation
      dependent MPRs. TIP47 is present in cytosol and on endosomes and is required for
      MPR transport from endosomes to the trans-Golgi network in vitro and in vivo.
      TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation
      dependent MPR that is essential for its proper sorting within the endosomal
      pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and
      facilitates their collection into transport vesicles destined for the Golgi.

PMID- 9590178
TI  - Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex
      specific gene expression.
AB  - Products of steroidogenic factor 1 (SF-1) and Wilms' tumor 1 (WT1) genes are
      essential for mammalian gonadogenesis prior to sexual differentiation. In males,
      SF-1 participates in sexual development by regulating expression of the
      polypeptide hormone Mullerian inhibiting substance (MIS). Here, we show that WT1 
      KTS isoforms associate and synergize with SF-1 to promote MIS expression. In
      contrast, WT1 missense mutations, associated with male pseudohermaphroditism in
      Denys-Drash syndrome, fail to synergize with SF-1. Additionally, the X-linked,
      candidate dosage-sensitive sex-reversal gene, Dax-1, antagonizes synergy between
      SF-1 and WT1, most likely through a direct interaction with SF-1. We propose that
      WT1 and Dax-1 functionally oppose each other in testis development by modulating
      SF-1-mediated transactivation.

PMID- 9590179
TI  - Odorant receptor localization to olfactory cilia is mediated by ODR-4, a novel
      membrane-associated protein.
AB  - Seven transmembrane domain receptors can be localized to different parts of the
      plasma membrane or to different intracellular compartments in a receptor-specific
      and cell type-specific fashion. We show here that the C. elegans genes odr-4 and
      odr-8 are required for localization of a subset of seven transmembrane domain
      odorant receptors to the cilia of olfactory neurons. Other cilia-signaling
      proteins, including ion channels, a G alpha protein, and even other receptor
      types, are localized via an odr-4/odr-8-independent pathway. odr-4 encodes a
      novel membrane protein that is expressed exclusively on intracellular membranes
      of chemosensory neurons, where it acts cell-autonomously to facilitate odorant
      receptor folding or localization.

PMID- 9590182
TI  - Pathogenesis of lupus nephritis and ANCA-associated systemic vasculitis: lessons
      from experimental models.

PMID- 9590180
TI  - Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen
      breakage syndrome.
AB  - Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal
      instability syndrome characterized by microcephaly, growth retardation,
      immunodeficiency, and cancer predisposition. Cells from NBS patients are
      hypersensitive to ionizing radiation with cytogenetic features indistinguishable
      from ataxia telangiectasia. We describe the positional cloning of a gene encoding
      a novel protein, nibrin. It contains two modules found in cell cycle checkpoint
      proteins, a forkhead-associated domain adjacent to a breast cancer carboxy
      terminal domain. A truncating 5 bp deletion was identified in the majority of NBS
      patients, carrying a conserved marker haplotype. Five further truncating
      mutations were identified in patients with other distinct haplotypes. The domains
      found in nibrin and the NBS phenotype suggest that this disorder is caused by
      defective responses to DNA double-strand breaks.

PMID- 9590181
TI  - The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of
      double-strand break repair to the cellular DNA damage response.
AB  - Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized
      by increased cancer incidence, cell cycle checkpoint defects, and ionizing
      radiation sensitivity. We have isolated the gene encoding p95, a member of the
      hMre11/hRad50 double-strand break repair complex. The p95 gene mapped to 8q21.3,
      the region that contains the NBS locus, and p95 was absent from NBS cells
      established from NBS patients. p95 deficiency in these cells completely abrogates
      the formation of hMre11/hRad50 ionizing radiation-induced foci. Comparison of the
      p95 cDNA to the NBS1 cDNA indicated that the p95 gene and NBS1 are identical. The
      implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct
      molecular link between DSB repair and cell cycle checkpoint functions.

PMID- 9590183
TI  - Potential of dopamine A-1 agonists in the management of acute renal failure.
AB  - Many therapeutic approaches have been undertaken both to prevent acute ischemic
      or nephrotoxic renal injury and, once acute renal failure (ARF) has developed, to
      improve renal function and reduce mortality. To date, most therapeutic studies
      have investigated the effects of diuretics (eg, mannitol, furosemide), vasoactive
      agents (calcium channel blockers, atrial natriuretic peptide), or dopamine (a
      nonselective dopaminergic agent [DAA]) in one or more phases of ARF.
      Unfortunately, studies of the use of DAA in ARF are complicated by the existence
      of at least two different DAA receptors (DA-1 and DA-2), and by the stimulation
      of alpha- and/or beta-adrenergic receptors by high doses of DAA. The undesirable
      side effects of high doses of dopamine and the inconclusive results using low
      doses (ie, "renal doses") of dopamine (a nonselective DAA) have prompted
      consideration of the use of more selective dopaminergic agonists for the
      prophylaxis and treatment of ARF. Selective DA-1 agonists exhibit many desirable
      renal effects that theoretically support their use for the prophylaxis and/or
      treatment of ARF, including decreases in renal vascular resistance accompanied by
      increases in renal blood flow and glomerular filtration rate, and increases in
      sodium excretion and urine volume. Even at high doses, some selective DA-1
      agonists, such as fenoldopam, do not stimulate DA-2 receptors, or adrenergic
      alpha- or beta-receptors, and thus are free of unwanted side effects (eg,
      arrhythmias). Results of several studies in normal and hypertensive humans, and a
      few studies in animal models, are consistent with the notion that DA-1 agonists
      may be useful in preventing or treating ARF. Careful randomized prospective
      clinical trials of DA-1 agonists in human ARF are needed to test this hypothesis.

PMID- 9590184
TI  - Pregnancy and dialysis.
AB  - The outcome of pregnancy in patients with end-stage renal failure has long been
      considered to be extremely poor, and the literature concerning pregnancy while on
      dialysis is rather scarce. We reviewed the records of five pregnancies in
      dialysis patients and performed a national survey on this topic. The dialysis
      technique and dialysis dose, the effects of erythropoietin (EPO), and the
      evolution of blood pressure levels in our patients are presented. The dose of EPO
      had to be increased to maintain the hemoglobin level at 10 to 11 g/dL. There was
      no case of EPO-related hypertension and no need for transfusion. The obstetric
      data of the national survey, including our own patients, were analyzed. The
      incidence of pregnancy going beyond the first trimester was 0.3 per 100 patient
      years (15 cases in 1,472 females of childbearing age treated, for a total of
      4,545 patient-years). In all but one patient initiating pregnancy while already
      on dialysis, the frequency and dose of dialysis were increased (to a weekly Kt/V
      of six to eight in our personal cases). The outcome was successful in 50% of
      pregnancies occurring in hemodialyzed patients and in 80% of patients who started
      dialysis after initiation of pregnancy. Polyhydramnios was found in eight of 13
      cases and growth retardation in two of nine cases. The incidence of low birth
      weight and prematurity was 100%, and cesarean section was performed in 66% of
      successful pregnancies. In successful pregnancies, we found a correlation between
      birth weight and dose of dialysis. Our findings confirm the remarkable
      improvement in the prognosis of pregnancy in dialysis patients in recent years.

PMID- 9590185
TI  - Registry of pregnancy in dialysis patients.
AB  - A total of 2,299 dialysis units listed by the Health Care Finance Administration
      were surveyed to determine the frequency and course of pregnancies in dialysis
      patients. The responses included 930 units caring for 6,230 females aged 14 to 44
      years (1,699 receiving peritoneal dialysis and 4,531 receiving hemodialysis). Two
      percent of the female patients of childbearing age became pregnant over a 4-year
      period (2.4% of the hemodialysis patients and 1.1% of the peritoneal dialysis
      patients). The infant survival rate was 40.2% in the 184 pregnancies in women who
      conceived after starting dialysis and 73.6% in the 57 pregnancies in women who
      started dialysis after conception. In the subset of women in whom dialysis
      modality was known, infant survival was not significantly different between the
      hemodialysis and peritoneal dialysis patients (39.5% v 37%). There was a trend
      toward better infant survival in women who received dialysis > or = 20 hours per
      week and a weak correlation between number of hours of dialysis and gestational
      age (P = 0.05). Maternal complications included two maternal deaths and five
      intensive care unit admissions for hypertensive crisis. Seventy-nine percent of
      women had some degree of hypertension, and 32 had blood pressure higher than
      170/110 mm Hg. Only 5.9% of women had a hematocrit greater than 30% throughout
      pregnancy. Twenty-six percent of women treated with erythropoietin (EPO) and 77%
      of women not receiving EPO required transfusions. Eleven infants had congenital
      anomalies and 11 had long-term medical problems. Eighty-four percent of infants
      born to women who conceived after starting dialysis were premature. The
      likelihood of a surviving infant resulting from pregnancy in dialysis patients is
      higher than previously observed. There is no preferred dialysis modality. There
      is a suggestion that increased dialysis time may improve outcome. Prematurity
      remains a major cause of morbidity and likely contributes to a high frequency of
      long-term medical problems in surviving infants.

PMID- 9590186
TI  - ACE gene polymorphism in childhood IgA nephropathy: association with
      clinicopathologic findings.
AB  - A deletion polymorphism in the angiotensin-converting enzyme (ACE) gene has been
      reported to be a risk factor for progression to chronic renal failure in
      immunoglobulin A nephropathy (IgAN). In this study, we investigated the
      association between ACE gene polymorphism and clinical findings, early biopsy
      findings such as the extent of mesangial proliferation, focal lesions (capsular
      adhesions, glomerulosclerosis, and crescents), and the glomerular area in
      childhood IgAN. Genomic DNA was obtained from 97 patients and control subjects.
      Gene polymorphisms, consisting of an insertion (I) or deletion (D) of the 287
      base pair Alu sequence, were detected using the polymerase chain reaction. The
      extent of capsular adhesions and glomerulosclerosis was significantly higher in
      patients with the ID/DD genotypes than in those with the II genotype (ID/DD v II:
      8.0%+/-1.4% v 2.5%+/-0.8% [P = 0.017] and 5.1%+/-1.3% v 1.4%+/-0.6% [P = 0.028],
      respectively). Whereas there was no difference in the extent of mesangial
      proliferation and crescents between the ID/DD genotypes and the II genotype.
      Urinary protein excretion at the time of biopsy was significantly greater in
      patients with the ID/DD genotypes than in those with the II genotype (1.02+/-0.15
      g/d/m2 body surface area v 0.56+/-0.13 g/d/m2 body surface area; P = 0.012).
      These results indicate that ACE gene polymorphism may not influence the extent of
      mesangial proliferation and crescents that are acute lesions. However, the ID/DD
      genotypes are associated with chronic lesions, such as capsular adhesions or
      glomerulosclerosis and urinary protein excretion in childhood IgAN.

PMID- 9590188
TI  - Nephrology nurse practitioners in a collaborative care model.
AB  - The use of nurse practitioners in the primary care setting is increasingly
      common. However, little information is available on their use in specialty care
      areas. This is especially true in nephrology, in which end-stage renal disease
      (ESRD) lends itself well to this type of practice. We describe our experience
      with a university-based collaborative care model for ESRD with nurse
      practitioners in nephrology. Our experience shows that nephrology nurse
      practitioners have a significant impact on extending the quality and quantity of
      patient care provided by the nephrologist. They facilitate a holistic patient
      friendly approach, and, as an integral part of the collaborative model, there is
      an associated significant decrease in patient mortality relative to standard
      comparators. Nurse practitioners provide a large amount of care for ESRD patients
      in a relatively independent fashion but under the supervision and with the
      collaborative interaction of nephrologists. Patient satisfaction, approval,
      respect, and trust for the nurse practitioners are exceptional. The use of
      nephrology nurse practitioners provides the potential for augmenting patient
      care, satisfaction, and access to care. It provides an avenue for potential cost
      reduction in nephrology while maintaining quality of care. It further provides a
      partial solution to the anticipated shortage of nephrologists in the twenty-first
      century.

PMID- 9590187
TI  - Renal effects of amphotericin B lipid complex.
AB  - A study was conducted to compare the renal effects of amphotericin B lipid
      complex (ABLC), a lipid formulation of the widely used antifungal medication,
      with conventional amphotericin B (AmB) in the treatment of serious fungal
      infections, including invasive candidiasis, cryptococcal meningitis, and
      aspergillosis. The clinical experience of ABLC includes two types of open-label
      studies: randomized comparative (ABLC 5 mg/kg/d compared with AmB 0.6 to 1 mg/kg)
      and emergency use. In the comparative studies, changes in serum creatinine were
      evaluated three ways: doubling of the baseline value, an increase from < or = 1.5
      mg/dL at baseline to > or = 1.5 mg/dL, and an increase from < or = 1.5 mg/dL at
      baseline to > or = 2.0 mg/dL. More patients in the AmB group reached these end
      points than in the ABLC group (P < or = 0.007), and the time needed to reach each
      of these end points was significantly shorter for the AmB group (P < or = 0.02).
      Increased serum creatinine was reported as an adverse event more frequently by
      patients receiving AmB than by patients receiving ABLC. In the emergency use
      study, a steady and statistically significant decrease in serum creatinine was
      observed among patients who started ABLC treatment with serum creatinine greater
      than 2.5 mg/dL due to prior AmB treatment. ABLC offers the physician a valuable,
      less-nephrotoxic alternative to AmB for the treatment of patients with severe,
      invasive fungal infections.

PMID- 9590189
TI  - Treatment strategies for insulin-dependent diabetics with ESRD: a cost
      effectiveness decision analysis model.
AB  - Clinical decision analysis has become an important tool for evaluating specific
      clinical scenarios and exploring public health policy issues. A decision analysis
      model that incorporates patient preferences regarding various outcomes, as well
      as cost, may be particularly informative in patients with type I diabetes and end
      stage renal disease (ESRD). Such a model that includes pancreas transplantation
      as a treatment choice has not been performed and is presented in this study. The
      decision tree consisted of a choice between four possible treatment strategies:
      dialysis, kidney-alone transplant from a cadaver (KA-CAD) or living donor (KA
      LD), and simultaneous pancreas-kidney (SPK) transplant. The analysis was based on
      a 5-year model, and the measures of outcome used in the model were cost and cost
      adjusted for quality of life. The measure of preference for quality of life was
      obtained using the "Standard Reference Gamble" method in 17 SPK transplant
      recipients who underwent transplantation between January, 1992 and June, 1996 at
      our center. The measures for various outcome states (mean +/- 1 SD) were dialysis
      free/insulin-free = 1, dialysis-free/insulin-dependent = 0.6 (0.4 to 0.8),
      dialysis-dependent/insulin-free = 0.5 (0.36 to 0.64), dialysis-dependent/insulin
      dependent = 0.4 (0.21 to 0.59), and death = 0. The expected 5-year costs for each
      of the treatment strategies in the model were dialysis, $216,068; KA-CAD
      transplant, $214,678; KA-LD transplant, $210,872; and SPK transplant, $241,207.
      The expected cost per quality-adjusted year for each of the treatment strategies
      in the model were dialysis, $317,746; KA-CAD transplant, $156,042; KA-LD
      transplant, $123,923; and SPK transplant, $102,422. SPK transplantation remained
      the optimal strategy after varying survival probabilities, costs, and utilities
      over plausible ranges by means of one-way sensitivity analysis. In conclusion,
      according to the 5-year cost-utility model presented in this study, SPK
      transplantation is the most cost-effective treatment strategy for a patient with
      type I diabetes and ESRD. From a policy standpoint, looking at the cost alone of
      pancreas transplantation is deceiving. In these patients, who may view various
      outcome states differently, it would be important to take into account cost
      adjusted for quality of life when evaluating this procedure.

PMID- 9590190
TI  - Is neuropeptide Y a contributor to volume-induced hypertension?
AB  - Hypertension often occurs with fluid overload. The most common mechanism is
      considered to be mediated by increased cardiac output. Hemodialysis (HD) patients
      frequently have large amounts of fluid overload. Neuropeptide Y (NPY) is
      activated by stress and contributes to hypertension and heart failure. We
      speculated that NPY may be released by the stress of fluid overload and, by its
      vasoconstrictor effect, may contribute to hypertension and heart failure. Plasma
      levels of NPY and other vasoconstrictors were studied in 20 HD patients with
      varying degrees of fluid overload, and the relationship of NPY plasma levels to
      blood pressure was analyzed. The plasma concentrations of NPY correlated with the
      degree of fluid overload (r = 0.89; P < 0.0001) and the mean arterial blood
      pressure (r = 0.85; P < 0.0001). Seven patients had fluid overload of greater
      than 6% of body weight. They had higher blood pressures and higher plasma
      concentrations of NPY than 13 HD patients with less than 5% of fluid retention
      (systolic blood pressure, 179+/-8.2 v 145+/-3.7 mm Hg, P = 0.007; NPY, 61+/-4.6 v
      26.8+/-2.7 pmol/L, P < 0.001). In stepwise multiple regression analysis, NPY
      alone explained blood pressure elevation when analyzed with fluid overload and
      angiotensin II, renin, noradrenaline, and adrenaline levels. We hypothesized that
      fluid overload in dialysis patients is a stress-inducing state that activates the
      sympathetic nervous system and releases the vasoconstrictor NPY. The resulting
      inappropriate vasoconstriction may contribute to volume-induced hypertension and
      heart failure in a vicious cycle. We conclude that determination of plasma NPY
      levels may be useful as a marker of the clinical threat of overhydration.

PMID- 9590192
TI  - Development of a patient classification system for chronic hemodialysis patients.
AB  - The purpose of this project was to develop a patient classification system that
      could indicate the caregiver time required by chronic hemodialysis patients
      during one dialysis treatment session. A patient acuity tool that used a
      condition indicator model was developed and validated. Initial indicator weights
      were established by an expert panel of 12 center directors. An experimental
      design was formulated that permitted evaluation of the influence of independent
      factors, such as type of ownership and cost-per-treatment environment on the
      acuity-time relationship. Acuity-time data were collected on more than 600
      individual treatments performed in 12 different centers across the country.
      Results indicate that patient acuity, measured by The American Nephrology Nurses'
      Association (ANNA)/MECON acuity tool, is a strong predictor of the caregiver time
      that will be required by the patient during that treatment session (P < 0.0001)
      and that centers differ in the amount of time that caregivers spend with patients
      who are rated at the same level of acuity (P = 0.001). The overall average time
      spent by caregivers ranged from 61 minutes per treatment for level I patients to
      97 minutes per treatment for level 5 patients. Ownership and cost-per-treatment
      effects were not significant as independent factors. However, some combinations
      of ownership and cost-per-treatment data may be significant.

PMID- 9590191
TI  - Enhanced production of nitric oxide may be involved in acute hypotension during
      maintenance hemodialysis.
AB  - To investigate the possible involvement of endogenous nitric oxide (NO) in acute
      hypotension during maintenance hemodialysis, we measured the plasma concentration
      of the nitrate anion NO3-, a stable metabolite of NO, in 19 patients undergoing
      hemodialysis. We analyzed heart rate variability to estimate the relationship
      between autonomic nervous activity and NO production, low-frequency/high
      frequency components (L/H) as a parameter of cardiac sympathetic activity, and
      high-frequency power as a parameter of cardiac vagal activity. Six patients
      developed severe hypotension (a change in mean blood pressure during dialysis >
      or = 20 mm Hg), four patients developed mild hypotension (a change in mean blood
      pressure < or = 19 mm Hg and > or = 1 mm Hg), and nine patients did not develop
      hypotension. The plasma levels of NO3- before dialysis were markedly elevated in
      the severely hypotensive group compared with the patients who showed no
      hypotension (566+/-122 micromol/L v 133+/-38 micromol/L; P < 0.01), and this
      difference disappeared midhemodialysis and after hemodialysis. The plasma
      concentration of NO3- before dialysis was significantly associated with both the
      change in mean blood pressure during dialysis (r= -0.735; P = 0.003) and the mean
      blood pressure after dialysis (r = -0.675; P = 0.0015). The L/H ratio was
      inhibited before or after dialysis in the severely hypotensive group compared
      with the nonhypotensive group, and hypotension during dialysis was correlated
      with the inhibited L/H ratio before (r = 0.784; P = 0.001) or after (r = 0.822; P
      = 0.001) dialysis. Plasma NO3- concentrations were correlated with the L/H ratio
      before (r = -0.553; P = .014) or after (r = -0.546; P = 0.015) dialysis. These
      results suggest that inhibited sympathetic activity is one of the causes of acute
      hypotension during dialysis, and the enhanced production of NO is involved in
      this inhibition of the sympathetic activity in patients having a hypotensive
      episode during dialysis. The plasma concentration of NO3- before dialysis may be
      a predictor of the risk of hypotension during dialysis in patients with end-stage
      renal disease.

PMID- 9590193
TI  - The other side of the coin: interdialytic weight gain as an index of good
      nutrition.
AB  - Excessive interdialytic weight gain (IDWG) is usually attributed to fluid and
      sodium overload. Abnormal thirst regulation, hormonal derangements, and social,
      cultural, and psychological habits may account for low compliance with fluid and
      salt restrictions. However, food intake is an important determinant of IDWG, and
      high IDWG may reflect the nutritional status of hemodialyzed patients, rather
      than their scanty compliance. The relationship between IDWG, efficacy of
      dialysis, and nutritional status was investigated in 38 patients (28 men and 10
      women), in whom urea kinetics was studied by means of an on-line urea sensor (UM
      1000, Baxter Healthcare, McGraw Park, IL), and Kt/V and protein catabolic rate
      (PCR) were calculated. Records from 161 dialysis sessions were analyzed and
      grouped according to their IDWG (group A, weight gain > 5% and group B, weight
      gain < 5% of dry body weight). In group A, Kt/V, solute removal index, urea
      reduction ratio, predialytic blood urea nitrogen (BUN), urea removed, and PCR
      were statistically higher than in group B (P < 0.05). Regression analysis showed
      a significant and positive correlation between IDWG and PCR. In 17 of 38 patients
      with steadily high IDWG, serum albumin levels, predialytic BUN, and PCR were
      significantly higher than in patients with low IDWG (P < 0.05). Sex and
      predialytic blood pressure did not correlate with IDWG; in contrast, age
      negatively affected both IDWG and PCR (age v IDWG and age v PCR, r = 0.22; P <
      0.008 and P < 0.006, respectively). These results confirm that high IDWG is
      associated with better nutritional status.

PMID- 9590194
TI  - Effect of an intravenous iron dextran regimen on iron stores, hemoglobin, and
      erythropoietin requirements in hemodialysis patients.
AB  - Iron deficiency is a common cause of delayed or diminished response to
      erythropoietin (EPO) in hemodialysis patients. Although oral iron is often
      prescribed to replete iron stores, this approach to iron supplementation may not
      be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an
      effective alternative approach to replete iron stores and may facilitate more
      cost-effective use of EPO. The purpose of this study was to evaluate an IV iron
      dextran regimen that consisted of a loading dose phase followed by monthly
      maintenance doses of iron dextran. The effect of this regimen on iron stores,
      hemoglobin, and EPO doses was evaluated. This was an open prospective study in
      adult hemodialysis patients who were iron deficient as defined by a serum
      ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%.
      Patients were loaded with 1 g iron dextran in five divided doses and then
      received monthly maintenance doses of 100 mg for the 4-month study period. Values
      of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month
      study period. Thirty hemodialysis patients receiving EPO were identified as being
      iron deficient and were enrolled in the study. The mean serum ferritin increased
      significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study
      period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P =
      0.002). Values for hemoglobin did not change significantly during the study
      period; however, there was a significant reduction in EPO dose from a mean
      baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P =
      0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in
      EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per
      year could be saved by use of IV iron dextran. The administration of the IV iron
      dextran regimen in the iron-deficient hemodialysis population was effective at
      repleting and maintaining iron stores and reducing EPO use.

PMID- 9590195
TI  - High-dose intradialytic urokinase to restore the patency of permanent central
      vein hemodialysis catheters.
AB  - From November 1, 1995, to April 30, 1997, in our outpatient dialysis facility,
      7,179 or 24.3% of hemodialyses were performed with soft, cuffed, intravenous
      catheters as blood accesses. Inadequate blood flow (pump speed < 400 mL/min) was
      noted in 286 instances (4.0%). Locking of catheter lumina with 5,000 to 9,000 IU
      urokinase was only partly successful in three of 21 cases. Infusions of 20,000 to
      40,000 IU urokinase in 25 instances during dialysis restored catheter function in
      10 cases. In nine instances in which blood could not be aspirated from the
      catheter and dialysis could not be performed, the infusion was done through the
      catheter while the patient remained in the chair. In eight instances, the
      catheter was opened, and dialysis was performed on the next shift. In 162
      instances, a new method was used to open failing catheters most conveniently,
      efficiently, and with minimal cost. Whenever a nonpositional deterioration of
      blood flow was noted, 250,000 IU urokinase was infused during dialysis over 3
      hours, if there were no contraindications. Full restoration of pump speed was
      achieved during 132 infusions; in another 21 cases, blood flow improved. In 59
      cases, in which an adequate pump speed was not achieved during the next dialysis,
      the infusion was repeated with restoration of blood flow in 50 instances and flow
      improvement in six; infusion was re-repeated in the nine instances without
      complete restoration of flow and in one of the 50 in which restoration of flow
      was temporary. Adequate flow was restored in nine of these 10 cases in which re
      repeated infusion was done. Routine doses of heparin were used concomitantly with
      urokinase in all cases. No adverse reaction to urokinase has been encountered in
      any case. To maintain long-term catheter patency, warfarin therapy was started in
      patients who required repeated urokinase infusions. Vials of 250,000 IU, 9,000
      IU, and 5,000 IU urokinase cost $358.47, $77.07, and $43.76, respectively. The
      higher cost of high-dose intradialytic urokinase as compared with the catheter
      "lock" is offset by the high probability of positive results, saving of nursing
      and patient time, and saving on transportation expenses. The convenience and cost
      are even more remarkably in favor of intradialytic urokinase compared with
      catheter stripping ($2,433) or surgical replacement ($3,060).

PMID- 9590197
TI  - Primary hyperaldosteronism causing posttransplantation hypertension: localization
      by adrenal vein sampling.
AB  - A 58 year-old man with end-stage renal disease who had received a cadaveric renal
      transplant presented with persistent hypertension and hypokalemia. Allograft
      renal artery stenosis, rejection, and cyclosporine effects were excluded.
      Hypokalemia persisted despite potassium supplementation and antihypertensive
      medications with hyperkalemic effects. The biochemical findings of primary
      hyperaldosteronism with a normal adrenal anatomy imaged by magnetic resonance
      imaging (MRI) necessitated adrenal vein sampling to lateralize a left adrenal
      adenoma. His hypokalemia was cured by the removal of the adenoma, and his blood
      pressure (BP) control was easily achieved with a less complex regimen of
      antihypertensives. We suggest that the concomitant existence of resistant
      hypokalemia and posttransplantation hypertension, especially in the cyclosporine
      era, should stimulate a search for hyperaldosteronism; once transplant renal
      artery stenosis has been excluded, the patient should be investigated for primary
      hyperaldosteronism. When imaging studies fail to show adrenal pathology, adrenal
      vein sampling will likely do so.

PMID- 9590196
TI  - Tuberculosis infection and anergy in hemodialysis patients.
AB  - Patients on hemodialysis are at increased risk for developing active tuberculosis
      (TB) after primary infection. Although this increased risk is well documented,
      the prevalence of TB infection, as indicated by a positive tuberculin skin test
      (TST), is not well described. End-stage renal disease is also known to be a risk
      factor for skin test anergy, but the rate of anergy in hemodialysis patients is
      unclear. We sought to identify rates of anergy and TST positivity in patients at
      four hemodialysis units in St Louis, Missouri, from June 1996 through August
      1996. Data obtained from patients and medical records included age, years on
      hemodialysis, medical history, and basic laboratory data. Patients without a
      history of TB or a positive TST had a TST with Tubersol, as well as candida and
      tetanus controls, placed by the Mantoux method. Tests were read 48 hours later.
      Of the patients enrolled at these units, 307 of 331 (93%) were evaluated.
      Patients had a mean age of 58 years (range, 19 to 91 years) and had been on
      hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made
      up 81% of the population. A history of a positive TST was obtained from 24
      patients (8%), and an additional seven (2%) had a history of active TB. Of the
      276 patients tested, 93 did not respond to either control antigen, but five of
      these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related
      to age, immunosuppressive drug use, and the reagents used, but not to urea
      reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients
      (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a
      positive TST or history of TB. TB or a positive TST was associated with liver
      disease and peptic ulcer disease, but not socioeconomic status. All 17 newly
      identified TST-positive patients received chest radiographs. No new cases of
      active TB were found. Only two of 17 of these patients (12%) were started on
      isoniazid (INH) prophylaxis. We identified high rates of TST positivity and
      anergy in the hemodialysis patients tested. Hemodialysis patients should receive
      regular TST screening, and INH prophylaxis needs to be more strongly encouraged.
      Studies are ongoing to define the rate of TST conversion over time.

PMID- 9590198
TI  - Acute renal failure in accidental hypothermia of cold water immersion.
AB  - We report a 27-year-old Japanese man who developed acute renal failure associated
      with cold water immersion. The clinical course was consistent with that of acute
      renal failure attributable to acute tubular necrosis. A renal biopsy specimen
      showed patchy and focal loss of tubule cells, necrotic epithelium, interstitial
      edema, and arterial lumina obstructed by diffuse and severe intimal thickening.
      Endothelin increased more than five times in the early phase of the clinical
      course. Vasoconstriction and ischemia induced by cold exposure seem to lead to
      endothelin release. Endothelin may be related to the development of acute renal
      failure and intimal thickening.

PMID- 9590199
TI  - Spontaneous splenic hemorrhage in a patient with Wegener's granulomatosis.
AB  - We report the occurrence of spontaneous splenic hemorrhage in a patient with
      Wegener's granulomatosis. Pulmonary infiltrates, hemoptysis, and crescentic
      glomerulonephritis were accompanied by a progressive splenic enlargement with
      minimal abdominal symptoms. Magnetic resonance imaging was particularly helpful.
      The spleen was removed by minimally invasive endoscopic surgery. Subcapsular
      hemorrhage had occurred because of splenic vasculitis. Postoperatively, a
      remission was achieved by a combination of high-dose corticosteroids and
      cyclophosphamide.

PMID- 9590200
TI  - More dialysis appears beneficial for pregnant ESRD patients (at least in Belgium)

PMID- 9590201
TI  - New JNC-6 guidelines. Joint National Committee.

PMID- 9590202
TI  - JNC redux. Joint National Committee.

PMID- 9590203
TI  - 'At least we do not feel guilty': Managing conflict with families over dialysis
      discontinuation.

PMID- 9590204
TI  - What is the relationship between metabolic acidosis and nutritional status in
      dialysis patients?

PMID- 9590205
TI  - Fever, thrombocytopenia, anasarca, and acute renal failure in a 50-year-old
      woman.

PMID- 9590206
TI  - Treatment of acute methanol intoxication with hemodialysis.

PMID- 9590207
TI  - Intravenous iron in pediatric patients.

PMID- 9590208
TI  - Follow-up on mycophenolate treatment of glomerular disease.

PMID- 9590210
TI  - The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1 upon
      tyrosine phosphorylation.
AB  - Activation signals of lymphocytes are negatively regulated by the membrane
      molecules carrying the immunoreceptor tyrosine-based inhibition motif (ITIM).
      Upon tyrosine phosphorylation, ITIMs recruit SH2-containing phosphatases such as
      SHP-1, resulting in down-modulation of cell activation. We showed that the
      cytoplasmic domain of the CD72 molecule carries an ITIM and is associated in
      vitro with SHP-1 upon tyrosine phosphorylation. Moreover, cross-linking of B cell
      Ag receptor (BCR) enhances both tyrosine phosphorylation of CD72 and association
      of CD72 with SHP-1 in B cell line WEHI-231. These results indicate that CD72
      recruits SHP-1 upon tyrosine phosphorylation induced by BCR signaling, suggesting
      that CD72 is a negative regulator of BCR signaling.

PMID- 9590209
TI  - Involvement of SHP-2 in multiple aspects of IL-2 signaling: evidence for a
      positive regulatory role.
AB  - Binding of IL-2 to its receptor activates several biochemical pathways, but
      precisely how these pathways are linked is incompletely understood. Here, we
      report that SHP-2, an SH2-domain containing tyrosine phosphatase, associates with
      different molecules of the IL-2 signaling cascade. Upon IL-2 stimulation, SHP-2
      was coimmunoprecipitated with Grb2 and the p85 subunit of phosphatidylinositol 3
      kinase. In contrast, SHP-2 was constitutively associated with JAK1 and JAK3.
      Finally, SHP-2 expression amplified STAT-dependent transcriptional activation
      whereas a dominant negative allele inhibited transactivation and the IL-2-induced
      activation of MAPK (mitogen-activated protein kinase). These results demonstrate
      the involvement of SHP-2 in multiple pathways of the IL-2 signaling cascade and
      provide evidence for its positive regulatory role.

PMID- 9590211
TI  - CD40 ligation prevents neonatal induction of transplantation tolerance.
AB  - To investigate the consequences of CD40 engagement on the neonatal induction of
      transplantation tolerance, BALB/c mice were injected at birth with (A/J x BALB/c)
      F1 spleen cells together with activating anti-CD40 mAb and grafted 4 wk later
      with A/J skin. Whereas A/J allografts were accepted in mice neonatally injected
      with F1 cells and control Ab, they were acutely rejected in mice injected with F1
      cells and anti-CD40 mAb. Neonatal administration of anti-CD40 mAb resulted in
      enhanced anti-A/J CTL activity, increased IFN-gamma, and decreased IL-4
      production by donor-specific T cells in vitro. Experiments using anti-cytokine
      mAb and IFN-gamma-deficient mice demonstrated that CD40 ligation prevents
      neonatal allotolerance through an IFN-gamma- and IL-12-dependent pathway.
      Finally, we found that newborn T cells express less CD40L than adult T cells upon
      TCR engagement. Taken together these data indicate that insufficiency of
      CD40/CD40L interactions contribute to neonatal transplantation tolerance.

PMID- 9590212
TI  - Microglia are more efficient than astrocytes in antigen processing and in Th1 but
      not Th2 cell activation.
AB  - Microglia and astrocytes, two glial cell populations of the central nervous
      system, present Ag and stimulate T cell proliferation, but it is unclear whether
      they preferentially activate Th1 or Th2 responses. We have investigated the
      efficiency of microglia and astrocytes in the presentation of OVA peptide 323-339
      or native OVA to Th1 and Th2 cell lines from DO11.10 TCR transgenic mice. Upon
      stimulation with IFN-gamma, microglia express MHC class II molecules, CD40, and
      ICAM-1 and efficiently present OVA 323-339, leading to T cell proliferation and
      production of IL-2 and IFN-gamma by Th1 and of IL-4 by Th2 cells. IFN-gamma
      treated astrocytes, which express MHC class II and ICAM-1, present OVA 323-339
      less efficiently to Th1 cells but are as efficient as microglia in inducing IL-4
      secretion by Th2 cells. However, astrocytes are much less potent than microglia
      in presenting naturally processed OVA peptide to either T cell subset, indicating
      inefficient Ag processing. The capacity of astrocytes and microglia to stimulate
      Th1 and Th2 cells depends on their MHC class II expression and does not involve
      ICAM-1, B7-1, or B7-2 molecules. However, CD40-CD40L interactions contribute to
      Th1 activation by microglia. These data suggest that microglia may play a role in
      the activation of Th1 and Th2 cells, whereas astrocytes would restimulate mainly
      Th2 responses in the presence of appropriate peptides. This differential capacity
      of brain APC to restimulate Th1 and Th2 responses may contribute to the
      reactivation and regulation of local inflammatory processes during infectious and
      autoimmune diseases.

PMID- 9590213
TI  - T and B cell development in BP-1/6C3/aminopeptidase A-deficient mice.
AB  - Stage-restricted expression of cell surface molecules serves to delineate B
      lineage cells during their progressive differentiation within the bone marrow.
      The BP-1/6C3 Ag, aminopeptidase A (APA), is selectively expressed by the pre-B
      and immature B cells. This ectoenzyme, which is also present on bone marrow
      derived stromal cells, thymic cortical epithelial cells, renal proximal tubular
      cells, intestinal enterocytes, and endothelial cells, cleaves acidic glutamyl and
      aspartyl residues from the N-terminus of angiotensin and other biologically
      active peptides to quench their functional activity. BP-1/6C3/APA expression by
      early B lineage cells is up-regulated by IL-7, an important growth factor for pre
      B cells and T cells. To explore the physiologic role of this peptidase, we
      generated a mouse model of BP-1 deficiency by gene targeting in embryonal stem
      cells. While mice homozygous for the BP-1 mutation did not express detectable BP
      1 protein or enzyme activity, they developed normally, generated normal numbers
      of T and B cells, exhibited integrity of Ab responses to both thymus-dependent
      and -independent Ags, and produced normal serum Ig levels. Phenotypic analysis of
      bone marrow and thymic lymphocytes indicated a normal pattern of B and T lineage
      differentiation. B lymphopoiesis in fetal liver cultures and the proliferative
      responses of bone marrow cells to IL-7 and LPS were also unimpaired. These
      findings indicate that BP-1 ectoenzyme activity is not essential for normal B and
      T cell development.

PMID- 9590214
TI  - Kinetics of establishing the memory B cell population as revealed by CD38
      expression.
AB  - In this report, we detail changes in the expression of CD38 on murine B cells
      during the course of a T cell-dependent immune response. CD38 is expressed on all
      naive B cells but is down-regulated on isotype-switched B cells from both the
      germinal centers (GCs) and the foci of Ab-forming cells which arise during the
      first weeks of the response. The down-regulation on GC B cells, however, is
      reversible since Ag-specific IgG1 B cells with high levels of CD38 are apparent
      by 2 wk postimmunization. These cells have characteristics that resemble
      recirculating memory B cells, in that they are small and bind low levels of
      peanut agglutinin. Such characteristics indicate that the restoration of CD38
      levels is coincidental with the transition from GC to memory B cell. Using this
      observation, we plotted the development of the memory population and the demise
      of the GC reaction as a function of time after immunization. Our results indicate
      that the GC reaction ceases gradually over many weeks rather than suddenly, which
      corresponds with the formation of the memory B cell population. Furthermore, by
      segregating memory B cells and GC B cells, it was possible to assess the in vitro
      survival characteristics of each compared with naive B cells. These experiments
      demonstrated that memory B cell survival in vitro was comparable with naive B
      cell survival but less than the survival seen for bcl-2-transgenic B cells,
      whereas GC B cell survival, as expected, was very poor. Hence, by resolving
      murine Ag-specific memory B cells and GC B cells, we have been able to quantify
      the development of the memory B cell population.

PMID- 9590215
TI  - DR/CLIP (class II-associated invariant chain peptides) and DR/peptide complexes
      colocalize in prelysosomes in human B lymphoblastoid cells.
AB  - In APCs, MHC class II molecules (MHC class II) bind antigenic peptides after HLA
      DM mediated removal of CLIP. To characterize intracellular sites of peptide
      loading in human B lymphoblastoid cell lines, we conducted immunoelectron
      microscopy studies with Abs recognizing MHC class II associated with CLIP or
      bound peptide, respectively, together with Abs to HLA-DM and endocytic markers.
      The distribution of these molecules indicates that peptide binding occurs in
      compartments with characteristics of normal late endosomes, and in compartments
      that show characteristics of late endosomes, but are not detectably accessed by
      endocytosed BSA-gold. The latter compartments may represent or give rise to
      recycling vesicles that deliver peptide-loaded class II molecules to the cell
      surface. In addition, we have compared cells in which HLA-DM and HLA-DR
      interaction is defective with cells in which this interaction is intact, and find
      that DM/DR interaction is not required for the proper localization of either
      molecule to peptide-loading compartments.

PMID- 9590216
TI  - In situ immune response in gut-associated lymphoid tissue (GALT) following oral
      antigen in TCR-transgenic mice.
AB  - Oral administration of Ag results in systemic hyporesponsiveness termed oral
      tolerance. The regulatory cells induced by oral Ag are effective in the
      suppression of Th1-type autoimmune diseases. We examined the cytokine
      microenvironment in gut-associated lymphoid tissue in response to orally
      administered OVA in OVA TCR-transgenic mice. Mice were fed a low (0.5 mg) or high
      (500 mg) dose of OVA one time or five times. Immunohistochemical analysis
      demonstrated increased IL-4, IL-10, and TGF-beta in the gut within 6 h of a low
      dose feeding and after five low-dose or high-dose feedings. IFN-gamma and IL-2
      either decreased or showed no change, with the exception of a small transient
      increase in IL-2 at 6 h after a low dose. Increases in IL-4 and IL-10 were found
      in the dome of the Peyer's patch, and increases in TGF-beta were observed in the
      interfollicular region and the villi. IL-10 was also substantially increased in
      the villi. IL-4 and IL-10 were produced predominately by CD4+ T cells. TGF-beta
      was found predominately in macrophages and CD4+ T cells. Peyer's patches had a
      marked up-regulation of TGF-beta mRNA as measured by RT-PCR. These results
      demonstrate the differential activation of cytokine production in discrete
      regions of gut-associated lymphoid tissue. The induction of cytokines known to
      inhibit autoimmune disease at the site of Ag absorption indicates an important
      role for the mucosal immune system in the establishment of oral tolerance.

PMID- 9590217
TI  - Direct evidence that functionally impaired CD4+ T cells persist in vivo following
      induction of peripheral tolerance.
AB  - A small population of CD4+ OVA-specific TCR transgenic T cells was tracked
      following the induction of peripheral tolerance by soluble Ag to address whether
      functionally unresponsive, or anergic T cells, persist in vivo for extended
      periods of time. Although injection of OVA peptide in the absence of adjuvant
      caused a transient expansion and deletion of the Ag-specific T cells, a
      population that showed signs of prior activation persisted in the lymphoid
      tissues for several months. These surviving OVA-specific T cells had long
      lasting, but reversible defects in their ability to proliferate in lymph nodes
      and secrete IL-2 and TNF-alpha in vivo following an antigenic challenge. These
      defects were not associated with the production of Th2-type cytokines or the
      capacity to suppress the clonal expansion of a bystander population of T cells
      present in the same lymph nodes. Therefore, our results provide direct evidence
      that a long-lived population of functionally impaired Ag-specific CD4+ T cells is
      generated in vivo after exposure to soluble Ag.

PMID- 9590218
TI  - Transplacental priming of the human immune system to environmental allergens:
      universal skewing of initial T cell responses toward the Th2 cytokine profile.
AB  - The expression of Th2-skewed immunity against soluble protein Ags present in the
      normal environment is recognized as the primary cause of allergic inflammation in
      atopics. In contrast, nonallergic normal individuals display low level Th1-skewed
      immunity against the same Ags ("allergens"), which is perceived as conferring
      protection against Th2-dependent allergic sensitization. The type of T cell
      memory that develops against these Ags is currently believed to be the result of
      complex interactions between environmental and genetic susceptibility factors,
      which occur postnatally when the naive immune system directly confronts the
      outside environment. The results of the present study challenge this general
      concept. We demonstrate here for the first time that Th2-skewed responses to
      common environmental allergens, comprising IL-4, IL-5, IL-6, IL-9, and IL-13, are
      present in virtually all newborn infants and are dominated by high level
      production of IL-10. Moreover, these responses are demonstrable within 24 h of
      culture initiation, arguing against a significant contribution from covert in
      vitro T cell priming and/or differentiation. These findings imply that the key
      etiologic factor in atopic disease may not be the initial acquisition of allergen
      specific Th2-skewed immunity per se, but instead may be the efficiency of immune
      deviation mechanisms, which in normal (nonatopic) individuals redirect these
      fetal immune responses toward the Th1 cytokine phenotype.

PMID- 9590219
TI  - A critical role for IL-18 in the proliferation and activation of NK1.1+ CD3-
      cells.
AB  - Like IL-12, IFN-gamma-inducing factor/IL-18 has been shown to stimulate T cells
      for IFN-gamma production and growth promotion. Considering the NK-stimulatory
      capacity of IL-12, we investigated the effect of IL-18 on NK lineage cells. A CD4
      CD8- surface Ig- Ia- fraction of freshly prepared C57BL/6 spleen cells
      proliferated strikingly in response to combinations of IL-12 + IL-18 or IL-2 + IL
      18, but not to the individual cytokines or IL-2 + IL-12. Cells proliferating in
      response to IL-2 + IL-18 were NK1.1+ CD3-, whereas IL-12 + IL-18-responsive cells
      were NK1.1- CD3-. Restimulation of the former cells with IL-12 + IL-18 or the
      latter cells with IL-2 + IL-18 resulted in the generation of NK1.1- CD3- or
      NK1.1+ CD3- cells, respectively. Moreover, a NK1.1+ CD3- CD4- CD8- surface Ig- Ia
      population isolated from spleen cells was found to form NK1.1+ CD3- or NK1.1-
      CD3- blasts by stimulation with IL-2 + IL-18 or IL-12 + IL-18, respectively, and
      the NK1.1 positivity on these blasts was again reversed after restimulation with
      an alternative combined stimulus. Both types of blasts produced enormously large
      amounts of IFN-gamma in response to IL-12 + IL-18 and exhibited strikingly high
      levels of NK activity. These results indicate that IL-18 plays an obligatory role
      in inducing proliferation and activation of NK1.1+ CD3- CD4- CD8- cells and that
      the expression of the NK1.1 marker is reversible, depending on the cytokine used
      for stimulation in combination with IL-18.

PMID- 9590220
TI  - Expression of bright at two distinct stages of B lymphocyte development.
AB  - The B cell regulator of Ig heavy chain transcription (Bright) is a DNA-binding
      protein that was originally discovered in a mature Ag-specific B cell line after
      stimulation with IL-5 and Ag. It binds to the intronic heavy chain enhancer and
      5' of the V1 S107 family V(H) promoter. Several studies suggested that Bright may
      increase transcription of the heavy chain locus, and expression in cell lines was
      limited to those representing mature B cells. We have now analyzed normal
      hemopoietic tissues for the expression of Bright during B lymphocyte
      differentiation. We expected to find Bright expression in a subset of mature
      spleen cells, but also observed Bright in a subset of normal B lymphocytic
      progenitors in both adult bone marrow (BM) and in fetal liver as early as day 12
      of gestation. Bright was also expressed in the small percentage of CD4(low) cells
      in the thymus that are newly arrived from the BM and are not yet committed to the
      T lymphocyte lineage, but was not observed at later stages of T cell
      differentiation in either the spleen or thymus. Bright mRNA was not detected in
      the immature B lymphocytes that initially populate the spleen after migration
      from the BM. In addition, new splice variants of Bright were observed in fetal
      tissues. Thus, Bright expression is highly regulated in normal murine lymphocytes
      and occurs both early and late during B cell differentiation. These findings may
      have important implications for the function of Bright in regulating Ig
      transcription.

PMID- 9590221
TI  - CpG motifs in bacterial DNA activate leukocytes through the pH-dependent
      generation of reactive oxygen species.
AB  - B cells and monocytes endocytose DNA into an acidified intracellular compartment.
      If this DNA contains unmethylated CpG dinucleotides in particular base contexts
      (CpG motifs), these leukocytes are rapidly activated. We now show that both B
      cell and monocyte-like cell line responses to DNA containing CpG motifs (CpG DNA)
      are sensitive to endosomal acidification inhibitors; they are completely blocked
      by bafilomycin A, chloroquine, and monensin. The specificity of these inhibitors
      is demonstrated by their failure to prevent responses to LPS, PMA, or ligation of
      CD40 or IgM. Acidification of endosomal CpG DNA is coupled to the rapid
      generation of intracellular reactive oxygen species. The CpG DNA-induced reactive
      oxygen species burst is linked to the degradation of IkappaB and the activation
      of NFkappaB, which induces leukocyte gene transcription and cytokine secretion.
      These studies demonstrate a novel pathway of leukocyte activation triggered by
      CpG motifs.

PMID- 9590222
TI  - Pairing of variable heavy and variable kappa chains in individual naive and
      memory B cells.
AB  - A functional Ig consists of two heterodimers each of which is composed of a heavy
      and a light chain. Although there is increasing knowledge about the events that
      govern the rearrangement of the genes encoding each individual chain, only very
      limited information is available about the mechanisms governing the pairing of
      variable heavy (V(H)) and variable light (V(L)) chains. Using a single cell PCR,
      we were able to obtain V(H) and Vkappa chains from 144 individual human
      CD19+/IgM+ B cells. Pairing of specific V(H) or Vkappa families was not observed,
      nor was the length or the amino acid composition of the CDR3s of V(H) and Vkappa
      chains in individual B cells similar. Comparison of V(H) and Vkappa genes in B
      cells in which one or both contained evidence of somatic hypermutation with those
      with no mutations revealed a significant decrease in the mean length of the V(H)
      CDR3. Moreover, there was a significant correlation between the frequencies of
      mutations in V(H) and Vkappa gene pairs in individual B cells. These results
      indicate that Ag-mediated selection as opposed to V(H)DJ(H) recombination or
      subsequent Ig chain pairing tended to approximate the CDR3 lengths and the
      frequency of mutations of V(H) and Vkappa in individual B cells.

PMID- 9590223
TI  - Differential activation of T cells by natural antigen peptide analogues:
      influence on autoimmune and alloimmune in vivo T cell responses.
AB  - Recent studies using synthetic altered peptide ligands (Analogues) have led to
      the fine dissection of TCR-mediated T cell functions elicited by Ag recognition.
      Certain Analogues behave as full agonists of the antigenic peptide while others
      are partial agonists in that they only trigger selected T cell functions.
      Additionally, peptide Analogues can behave as antagonists by inhibiting functions
      of T cell clones when coincubated with the wild-type peptide. In fetal thymic
      organ cultures, synthetic altered peptide ligands can impact T cell repertoire
      selection. However, the influence of naturally occurring peptide Analogues on T
      cell immunity in vivo remains hypothetical. We previously reported that, in B10.A
      mice, immunogenicity and tolerogenicity of the self-MHC class I peptide, Ld 61
      80, were influenced by the presentation of a cross-reactive self-peptide, Kk 61
      80. Here, we show that Kk 61-80 self-peptide represents a partial agonist of Ld
      61-80 in that it induced the proliferation but not the lymphokine production of
      Ld 61-80-primed T cells. Next, we showed that presentation of Kk 61-80 Analogue
      peptide mediated T cell tolerance toward Ld 61-80 self-peptide. Alternatively,
      when Ld protein represented an alloantigen displayed on transplanted cells,
      immunization with Kk 61-80 Analogue sensitized recipient mice to Ld 61-80
      peptide, thus inducing potent immune responses to donor cells. These results show
      that the presentation of natural Analogue peptides may represent an essential
      component of T cell responses involved in autoimmunity and transplant rejection.

PMID- 9590224
TI  - Enhanced B-1 cell development, but impaired IgG antibody responses in mice
      deficient in secreted IgM.
AB  - The role of endogenous natural IgM in promoting the adaptive Ab response was
      investigated in newly constructed mutant mice in which B cells do not secrete IgM
      but still express surface IgM and IgD and undergo class switching to express
      other Ig isotypes. While the mutant mice had relatively normal numbers of
      conventional B (B-2) cells in all tissues examined, unexpectedly, B-1 cells in
      the peritoneum and spleen were approximately threefold more abundant. The
      elevated levels of B-1 cells were already detectable at 4 wk of age and were
      stably maintained throughout life. The levels of serum IgG2a, IgG3, and IgA were
      also elevated in the mutant mice at an early age. IgG2a response to a T cell
      independent Ag was augmented, whereas IgG Ab responses to suboptimal doses of a T
      cell-dependent Ag were impaired. The latter defect was associated with fewer
      splenic germinal centers, impaired Ab affinity maturation, and less Ag trapping
      on follicular dendritic cells. Together, these findings demonstrate a physiologic
      role of natural IgM in the feedback regulation of B-1 cell development, the
      regulation of IgG2a production, and the promotion of efficient B-2 cell Ab
      responses.

PMID- 9590225
TI  - Affinity maturation in Lyn kinase-deficient mice with defective germinal center
      formation.
AB  - Lyn kinase-deficient (lyn-/-) mice show several abnormalities such as reduced
      numbers of circulating B cells, hyper-IgM, and low proliferative responses
      induced by CD40 ligand. Lyn-/- mice also develop splenomegaly, produce
      autoreactive Abs with age, and finally develop glomerulonephritis. Another
      abnormality observed in lyn-/- mice is that their disability to form germinal
      centers (GCs). It has been considered that GCs play an important role in affinity
      maturation and differentiation to B cell memory upon immunization with thymus
      dependent Ag. Since Lyn kinase has been thought to be downstream of the signals
      from the B cell Ag receptor as well as CD40, we studied whether or not lyn-/-
      mice could exhibit normal Ag-specific class switching and affinity maturation
      following somatic hypermutation. The mice were immunized with (4-hydroxy-3
      nitrophenyl)acetyl-chicken gamma-globulin (NP-CG). Production of NP-specific IgG1
      Abs was slightly reduced but clearly detectable. The affinity of Abs produced was
      comparable to that in wild-type mice. Furthermore, somatic hypermutation occurred
      in the heavy-chain variable region at the same level as that in wild-type mice.
      Therefore, we conclude that isotype switching and affinity maturation occur
      normally in lyn-/- mice without the formation of GCs. The results lead to a
      speculation that Lyn may not play a role in induction of isotype switching or
      affinity maturation, despite being downstream of the signals from the B cell Ag
      receptor complex and CD40, and that GC architecture may not be absolutely
      essential for affinity maturation.

PMID- 9590226
TI  - Induction of tolerance in B-1 cells for bromelain-treated mouse red blood cells
      by a transient presence of anti-idiotype antibodies in neonatal and adult mice.
AB  - Murine B-1 cells are thought to develop from Ig- progenitors early in ontogeny
      and to expand by self-renewal. To examine the early development of Ig+ precursors
      of B-1 cells for bromelain-treated mouse RBC, the transient presence of RidA, a
      rat anti-Id mAb for V(H)11/Vkappa9-type anti-bromelain-treated mouse Abs, was
      produced in neonatal mice. The presence of RidA during days 0 to 10 of age
      resulted in an 80% reduction in peritoneal RidA-Id+ B cells and B cells secreting
      RidA-Id+ Ig after LPS stimulation in 8-wk-old mice. This suggests that most Ig+
      precursors for adult RidA-Id+ B cells already exist in 10-d-old mice. However,
      RidA injected into mice on day 10 had to persist for >4 days to result in a
      significant reduction in adult B cells. Similarly, although RidA injected into
      adult mice bound immediately to membrane Ig (mIg) of the peritoneal RidA-Id+ B
      cells, a RidA persistence for >4 days was required to suppress LPS reactivity of
      peritoneal and splenic B cells. The binding of RidA to mIg preexisting on B cells
      has no apparent effect on the ability of neonatal B cells to expand clonally or
      on the ability of adult B cells to secrete RidA-Id+ Ig after LPS stimulation.
      Both abilities evidently are suppressed by the accumulation of reaction between
      freshly expressed mIg and RidA.

PMID- 9590227
TI  - Flt3 ligand plus IL-7 supports the expansion of murine thymic B cell progenitors
      that can mature intrathymically.
AB  - Flt3 ligand (flt3L) has potent effects on hemopoietic progenitors, dendritic
      cells, and B lymphopoiesis. We have investigated the effects of flt3L on
      intrathymic precursors. The addition of flt3L + IL-7 to lobe submersion cultures
      of murine fetal thymic lobes resulted in the expansion of an immature population
      of Thy-1(low), CD44(high), HSA(high) cells. This population contained cells with
      precursor activity, as determined by their capacity to repopulate deoxyguanosine
      treated fetal thymic lobes. Upon reentry to the thymic lobe, flt3L + IL-7
      cultured Thy-1(low), CD44(high), HSA(high) cells underwent expansion and
      differentiation into B cells. Two weeks after fetal thymic organ culture
      following thymic lobe reconstitution, intrathymic cells were Thy-1-, B220+, and a
      subset was sIgM+. The intrathymic B cells shared features of adult thymic B
      cells, including CD5 expression and proliferative responses to IL-4 + IL-5 + CD40
      ligand, but not to LPS or soluble anti-IgM. Ig production was noted upon
      stimulation with IL-4 + IL-5 + LPS and IL-4 + IL-5 + CD40 ligand. In conclusion,
      we have demonstrated that flt3L + IL-7 supports the expansion of a subset of
      progenitors present in the fetal thymus. The cultured progenitors can repopulate
      a fetal thymic lobe and develop into mature functional B cells, demonstrating
      that the fetal thymus is able to support B cell as well as T cell development.

PMID- 9590228
TI  - Consequences of intrathymic TCR engagement by partial agonist on selection events
      and peripheral T cell activation program.
AB  - Functions elicited from mature T cells depend on the nature of the Ag. Thus, an
      agonist induces a larger set of cytokine responses than a partial agonist.
      Additionally, Ags present in the thymus influence both the selection of TCRs
      generated by gene rearrangement and the potential functional program of
      developing thymocytes. This can be approached by analysing the development of T
      cells in mice expressing the same transgenic TCR (tgTCR) under different
      conditions of intrathymic selection. H-2Kbm8 was found to act as a partial
      agonist for CD8+ T cells expressing a tgTCR specific for the H-2Kb alloantigen.
      Intrathymic exposure to full or to partial agonist affected the development of
      thymocytes at different stages, consistent with the respective CD8-independent
      and -dependent characteristic of the tgTCR/Ag interaction. The presence of the
      partial agonist led to the accumulation of a major population of thymocytes
      (tgTCR(high) CD4- CD8(low)) originating from TCR engagement at the immature
      single-positive CD8(low) stage as evidenced by: 1) results from reaggregated
      thymic organ culture in the presence of H-2(k/bm8) thymic stromal cells; 2) the
      absence of CD4+ thymocytes, the development of which depends on rearrangements of
      endogenous TCR alpha genes; and 3) the identification of the CD8(low) thymocytes
      as cycling cells. Peripheral CD8(low) T cells selected in an H-2(k/bm8) thymus
      expressed a partial functional program in response to H-2Kb, akin to the response
      of CD8(high) T cells to a partial agonist. The analysis of the molecular bases
      for partial reactivity revealed a correlation with inefficient AP-1, but
      efficient NF-kappaB transactivation.

PMID- 9590229
TI  - A critical role for IL-4 in regulating disease severity in experimental allergic
      encephalomyelitis as demonstrated in IL-4-deficient C57BL/6 mice and BALB/c mice.
AB  - Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune
      disease of the central nervous system (CNS) that has served as the principal
      experimental model for multiple sclerosis (MS). Susceptibility to disease is
      thought to correlate with the ability to generate a Th1-type cytokine profile in
      myelin-responsive T cells, whereas T cells producing a Th2 cytokine pattern, in
      particular IL-4, are thought to be nonencephalitogenic and also to confer
      protection against a Th1-type response. However, recent studies using a variety
      of genetically engineered animals in which the genes for Th1-type cytokines
      and/or their receptors have been inactivated have called into question the Th1
      Th2 paradigm in experimental allergic encephalomyelitis. In this report we have
      addressed the contribution of IL-4 to disease expression by studying two strains
      of mice, C57BL/6 and BALB/c, in which the gene for IL-4 has been inactivated. The
      IL-4-deficient C57BL/6 mice, and to a lesser extent the IL-4-deficient BALB/c
      mice, developed a more severe form of clinical disease, a more extensive
      pathologic involvement of the spinal cord, and an increased expression of
      proinflammatory cytokines in the CNS than their wild-type littermates. BALB/c and
      C57BL/6 mice showed a slightly different cytokine profile in the CNS. Both groups
      of animals recovered from the acute clinical episode in a time frame that was
      essentially identical to that found in the wild-type controls. We conclude that
      IL-4 plays an important role in modulating the severity of the encephalitogenic
      process, but does not by itself contribute to spontaneous remission from the
      disease.

PMID- 9590230
TI  - Activated rat macrophages produce a galectin-1-like protein that induces
      apoptosis of T cells: biochemical and functional characterization.
AB  - Galectins, a family of closely related beta-galactoside-binding proteins, show
      specific immunomodulatory properties. We have recently identified the presence of
      a galectin-like protein in rat peritoneal macrophages by means of a cross
      reactivity with a polyclonal Ab raised against a galectin purified from adult
      chicken liver. Galectin expression was up-regulated in inflammatory and activated
      macrophages, revealing a significant increase in phorbol ester- and
      formylmethionine oligopeptide-treated cells. In an attempt to further explore its
      functional significance, rat macrophage galectin was purified from activated
      macrophages by a single-step affinity chromatography on a lactosyl-Sepharose
      matrix. The eluted fraction was resolved as a single protein band of
      approximately 15,000 Da by SDS-PAGE that immunoreacted strongly with the anti
      chicken galectin serum. Gel filtration studies revealed that the protein behaved
      like a dimer under native conditions, and saccharides bearing a beta-D
      galactoside configuration were able to inhibit the hemagglutinating activity
      displayed by the purified galectin. In agreement with its isoelectric point of
      approximately 4.8, the amino acid analysis showed a definitive acidic pattern.
      Internal amino acid sequencing of selected peptides obtained by proteolytic
      cleavage revealed that this carbohydrate-binding protein shares all the
      absolutely preserved and critical residues found in other members of the
      mammalian galectin-1 subfamily. Finally, biochemical and ultrastructural
      evidence, obtained by genomic DNA fragmentation and transmission electron
      microscopy, are also provided to show its potential implications in the apoptotic
      program of T cells. This effect was quantified by using the terminal
      deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling assay and was
      found to be associated to the specific carbohydrate-binding properties of
      galectin.

PMID- 9590231
TI  - Partial TCR signals delivered by FcR-nonbinding anti-CD3 monoclonal antibodies
      differentially regulate individual Th subsets.
AB  - Anti-CD3 mAbs with low FcR affinity prolong graft survival in the absence of the
      cytokine-mediated toxicity observed with conventional anti-CD3 treatment.
      Previous studies have shown that FcR-nonbinding anti-CD3 mAbs suppress immune
      responses, at least in part, by delivering a partial signal resulting in Th1
      unresponsiveness. In this study, the biochemical and functional consequences of
      FcR-nonbinding anti-CD3 treatment for various activated T cell populations were
      examined. In contrast to Th1 cells, FcR-nonbinding anti-CD3-treated Th2 cells
      secreted IL-4 and proliferated. Furthermore, Th2 cells cultured with the mAb were
      not rendered unresponsive. Mixed "Th0" populations responded to FcR-nonbinding
      anti-CD3 by producing IL-4, and showed a selective decrease in IL-2 production
      following preculture with the mAb. The stimulation of IL-4-producing cells did
      not reflect a more complete TCR signal, since similar defects in zeta, ZAP-70,
      and MAP kinase phosphorylation were observed in Th1 and Th2 cells. Despite the
      proximal signaling defects, FcR-nonbinding anti-CD3 induced nuclear translocation
      of NF-ATc. Thus, Abs that deliver partial TCR signals may promote development of
      a Th2 phenotype during the course of an immune response via selective effects on
      different Th subsets.

PMID- 9590232
TI  - Phosphorylation regulates the delivery of MHC class II invariant chain complexes
      to antigen processing compartments.
AB  - Transport of newly synthesized MHC class II glycoproteins to endosomal Ag
      processing compartments is mediated by their association with the invariant chain
      (Ii). Targeting to these compartments is dependent upon recognition of leucine
      based endo. somal/lysosomal targeting motifs in the Ii cytosolic domain. Ii, like
      many molecules that contain leucine-based endosomal targeting motifs, is
      phosphorylated in vivo. In this report we demonstrate that the cytosolic domain
      of the p35 Ii isoform is phosphorylated in class II Ii complexes isolated from
      human B lymphoblastoid cell lines or freshly obtained PBMC. Mutation of serine
      residue 6 or 8 prevents phosphorylation of Ii-p35 expressed in HeLa cells.
      Treatment of B lymphoblastoid cell lines with the serine/threonine kinase
      inhibitor staurosporine prevented Ii phosphorylation and significantly delayed
      trafficking of newly synthesized class II Ii complexes to endosomal Ag processing
      compartments. By contrast, staurosporine had no effect on the rate of transport
      of class I or class II glycoproteins through the Golgi apparatus and did not
      inhibit the delivery of the chimeric molecule Tac-DM, to endocytic compartments,
      suggesting that staurosporine does not nonspecifically inhibit protein transport
      to the endocytic pathway. These results demonstrate that phosphorylation
      regulates the efficient targeting of MHC class II Ii complexes to Ag processing
      compartments and strongly suggest that this effect is mediated by phosphorylation
      of the MHC class II-associated Ii chain.

PMID- 9590233
TI  - Dissociation of proteasomal degradation of biosynthesized viral proteins from
      generation of MHC class I-associated antigenic peptides.
AB  - To study the role of proteasomes in Ag presentation, we analyzed the effects of
      proteasome inhibitors Cbz-Leu-Leu-Leucinal and lactacystin on the ability of
      mouse fibroblast cells to present recombinant vaccinia virus gene products to MHC
      class I-restricted T cells. The effects of the inhibitors depended on the
      determinant analyzed. For influenza virus nucleoprotein (NP), presentation of the
      immunodominant Kk-restricted determinant (NP(50-57)) was marginally inhibited,
      whereas presentation of the immunodominant Kd-restricted determinant (NP(147
      155)) was enhanced, particularly by lactacystin. Biochemical purification of
      peptides confirmed that lactacystin enhanced the generation of Kd-NP(147-155)
      complexes fourfold. Lactacystin also enhanced the recovery of one Kd-restricted
      vaccinia virus determinant from HPLC fractions, while inhibiting recovery of
      another. The inhibitors were used at sufficient concentrations to block
      presentation of biosynthesized full-length OVA and to completely stabilize a
      rapidly degraded chimeric ubiquitin-NP fusion protein. Strikingly, presentation
      of antigenic peptides from this protein was unaffected by proteasome inhibitors.
      We also observed that proteasome inhibitors induced expression of cytosolic and
      endoplasmic reticulum stress-responsive proteins. These data demonstrate first
      that the processes of protein degradation and generation of antigenic peptides
      from cytosolic proteins can be dissociated, and second that effects of proteasome
      inhibitors on Ag presentation may reflect secondary effects on cellular
      metabolism.

PMID- 9590234
TI  - Modulation of T cell cytokine profiles and peptide-MHC complex availability in
      vivo by delivery to scavenger receptors via antigen maleylation.
AB  - We have previously shown that conversion of proteins to scavenger receptor (SR)
      ligands by maleylation increases their immunogenicity. We now show that maleyl-Ag
      immune spleen cells make relatively more IFN-gamma and less IL-4 or IL-10 than
      native Ag-immune cells. This is also reflected in the IgG1:IgG2a ratios in Abs
      generated in vivo. SR engagement on macrophages does not alter their surface
      levels of the adhesive/costimulatory molecules CD11a/CD18, CD11b/CD18, CD24,
      CD54, or CD40, nor does it enhance their ability to support anti-CD3-driven
      proliferation of naive T cells in vitro. Costimulatory molecules implicated in
      differential Th1/Th2 commitment--CD80, CD86, and IL-12--are not inducible by SR
      ligation. In addition to macrophages and dendritic cells, B cells also show
      receptor-mediated uptake and enhanced presentation of maleyl-Ags. Using a
      monoclonal T cell line to detect peptide-MHC complexes expressed on spleen cells
      in Ag-injected mice, we find that higher levels of these complexes are generated
      in vivo from maleyl-proteins and they persist longer than those generated from
      the native protein. Together, these data suggest that in certain situations, the
      levels of cognate ligand available and/or the time course of their availability
      may play a major role in determining the cytokine profiles of the responding T
      cells in addition to the costimulatory signals implicated so far.

PMID- 9590235
TI  - Phosphorylation of FADD/MORT1 and Fas by kinases that associate with the membrane
      proximal cytoplasmic domain of Fas.
AB  - Fas (Apo-1, CD95), a member of the TNFR family, is expressed on a variety of cell
      types and transduces an apoptotic signal. Since Fas does not possess known
      enzymatic activities, proteins that interact with the cytoplasmic domain of Fas
      regulate the death signal. Several proteins have been identified, primarily using
      the yeast two-hybrid system, that associate with the death domain of Fas. One of
      these proteins, FADD/MORT1, can be phosphorylated, although the kinase that is
      responsible has not been identified. Furthermore, direct signaling connections
      between Fas and its known activation of sphingomyelinase or NF-kappaB have not
      been made, suggesting that other proteins may associate with Fas. In this study,
      a series of glutathione S-transferase fusion proteins was constructed that
      contained the cytoplasmic domain of murine Fas. These proteins were used to
      search for additional proteins that associate with Fas. Novel proteins, including
      kinases, were identified that associated specifically with the membrane-proximal,
      cytoplasmic tail of Fas but not with the death domain. One of these kinases
      phosphorylates FADD/MORT1. Moreover, the membrane-proximal region of Fas itself
      was phosphorylated by one of the associating kinases. These findings suggest
      that, similar to the Fas-related p55 TNFR, the membrane-proximal region of Fas
      likely participates in signaling.

PMID- 9590236
TI  - Respiratory syncytial virus-infected pulmonary epithelial cells induce eosinophil
      degranulation by a CD18-mediated mechanism.
AB  - Respiratory syncytial virus (RSV)-induced bronchiolitis in infants is
      characterized by wheezing, respiratory distress, and the histologic findings of
      necrosis and sloughing of airway epithelium. High concentrations of eosinophil
      cationic protein (ECP), a cytotoxic protein contained in the granules of
      eosinophils, have been found in the airways of RSV-infected infants. The
      mechanisms of eosinophil degranulation in vivo remain largely unknown. Since RSV
      infected respiratory epithelial cells are a rich source of cytokines with
      eosinophil-activating properties, our studies were designed to mimic in vitro the
      interaction between RSV, pulmonary epithelial cells (A549), and eosinophils in
      the airway mucosa. We report in this work that, in the absence of epithelial
      cells, neither RSV, in the form of purified virions, nor UV-irradiated culture
      supernatant of RSV-infected epithelial cells (RSV-CM) induced eosinophil
      degranulation. On the other hand, eosinophils released significant amount of ECP
      when cultured with RSV-infected A549 cells. Uninfected A549 cells, which failed
      to induce eosinophil degranulation, were equally effective in triggering ECP
      release if they were cultured with eosinophils in the presence of RSV-CM.
      Although RSV-CM induced the up-regulation of the beta2 integrin CD11b on
      eosinophils and the expression of ICAM-1 on A549 cells, release of ECP was
      inhibited significantly by anti-CD18 mAb, but not by anti-ICAM-1 mAb. These
      results suggest a novel mechanism by which respiratory viruses may trigger the
      detrimental release of eosinophil granule proteins in the airway mucosa.

PMID- 9590237
TI  - 3' IgH enhancer elements shift synergistic interactions during B cell
      development.
AB  - IgH gene expression is tightly controlled over the course of B cell development,
      B cell activation, and the subsequent differentiation of these cells into Ig
      secreting plasmacytes. There are several transcriptional enhancers that map
      within and downstream of the IgH locus, and some of these have been clearly
      implicated in the developmental regulation of IgH gene assembly and expression.
      While some of the individual enhancers from this locus have been studied
      extensively, the functional interactions possible among this group of enhancers
      have been largely unexplored. In the present study, we have measured the
      transcriptional activities of combinations of enhancers introduced into B-lineage
      cell lines at several different developmental stages. We detected a developmental
      progression in which the 3' enhancers are initially inactive, then become
      strongly active through synergistic interactions, and finally achieve a strong
      level of activity with little interdependency. The relative contributions of E mu
      (the intron enhancer) and of the 3' enhancers also change as a function of
      developmental stage. We discuss these results in light of parallel studies of
      developmental changes in transcription factor requirements.

PMID- 9590238
TI  - Rearrangement and selection in the developing Vkappa repertoire of the mouse: an
      analysis of the usage of two Vkappa gene segments.
AB  - Detailed analysis of the rearrangement and expression of two mouse Vkappa genes
      has been used to examine B cell repertoire development. The Vkappa1-A gene is
      used by a large proportion (9.6%) of splenic B cells in the adult primary
      repertoire, whereas the Vkappa22 gene is used at a much lower frequency (0.16%).
      Consistent with these results, quantitative PCR (Q-PCR) assays revealed that the
      number of splenic B cells with rearranged Vkappa1-A genes is much greater than
      the number with rearranged Vkappa22 genes. Q-PCR was also performed on both
      normal bone marrow pre-B cells and transformed pre-B cells induced to rearrange
      their kappa loci at high frequency. In contrast to splenic B cell rearrangements,
      the numbers of Vkappa1-A and Vkappa22 rearrangements in pre-B cells differ by
      only two- or threefold, suggesting that the intrinsic rearrangement frequencies
      of these two Vkappa genes are not significantly different. Further evidence of
      disproportionate selection was obtained by comparing the percentages of
      productive rearrangements amplified from genomic splenic DNA. Sequence analysis
      showed 84% (37 of 44) of the Vkappa1-A rearrangements but only 57% (29 of 51) of
      the Vkappa22 rearrangements to be in-frame. Together these results suggest that B
      cells expressing Vkappa1-A-encoded light chains are preferentially selected
      either in the periphery or in the transition from pre-B to B cell. Sequence data
      also reveal a surprisingly restricted diversity of VJ junctions, apparently due
      to biases introduced by the rearrangement mechanism.

PMID- 9590239
TI  - Activation of the CD2 pathway in lamina propria T cells up-regulates functionally
      active AP-1 binding to the IL-2 promoter, resulting in messenger RNA
      transcription and IL-2 secretion.
AB  - The aim of this study was to identify molecular mechanisms involved in
      transcriptional regulation of IL-2 expression following CD2 and CD3 activation in
      lamina propria (LP) T cells. Studies used T cells from normal, ulcerative
      colitis, and Crohn's disease mucosa and freshly isolated PBMC, PBMC stimulated
      with IL-2 alone, and PBMC stimulated with IL-2 and cocultured with B cell lines
      (LP-like T cells). Electrophoretic mobility shift assays were performed with
      nuclear extracts from cells activated with either anti-CD2 or anti-CD3 Abs. CD2
      signaling in LPMC and LP-like T cells led to a pattern of sustained up-regulation
      of AP-1-binding complexes, whereas CD3 activation resulted in only transient up
      regulation. While the pattern of regulation of AP-1 binding observed in normal,
      uninflamed, or inflamed Crohn's disease LPMC is similar, differences in intensity
      of AP-1 binding were observed. Activation of LP-like T cells mimics the up
      regulation of AP-1 with a kinetic profile similar to that observed with freshly
      isolated LPMC from Crohn's disease-inflamed tissue. The AP-1 complex formed
      following CD2 activation is composed of jun/fos heterodimers. The CD2-enhanced
      responsiveness is reflected in functional analysis experiments utilizing
      transfection of both multimeric-TRE or IL-2 promoter-luciferase constructs
      directly into normal, ulcerative colitis, or Crohn's disease LPMC. Our data
      suggest that activation of LP T cells from normal, ulcerative colitis, or Crohn's
      disease mucosa through the CD2 pathway leads to induction of AP-1 complexes that
      bind to the IL-2 promoter, and may play a pivotal role in modulating IL-2
      production in the gut.

PMID- 9590241
TI  - Polymorphism in the Ialpha1 germ-line transcript regulatory region and IgA
      productivity in patients with IgA nephropathy.
AB  - Enhanced in vivo and in vitro production of IgA has been reported in patients
      with IgA nephropathy (IgAN) and their family members. It is generally considered
      that IgA1 is a prominent subclass of IgA in IgAN. Although genetic mechanisms of
      IgA class switch recombination in IgAN have been studied enthusiastically, the
      critical factors that induce IgA1-specific class switching in IgAN have yet to be
      elucidated. A large body of data indicates that the germ-line transcript of Ig
      constant region (C(H)) genes that precedes actual class switching has regulatory
      effects on class switch recombination. To analyze structural abnormalities in the
      Ialpha1 germ-line transcript regulatory gene, a region about 1000 bp long located
      upstream of Ialpha1 exons was surveyed by the PCR-single strand conformation
      polymorphism method, and the polymorphism detected was confirmed by subsequent
      DNA sequencing. Three hot spots for point mutation were detected upstream of the
      promoter region of the Ialpha1 germ-line transcript, and the mutations were
      observed more frequently in patients than in controls. Patients with the
      mutations showed higher levels of serum IgA and higher in vitro IgA synthesis. In
      the luciferase assay, the regulatory gene with the mutations showed a potent
      effect for induction of the Ialpha1 germ-line transcript. The polymorphism in the
      Ialpha1 regulatory region possibly causes enhanced IgA production in some
      patients with IgAN.

PMID- 9590240
TI  - Characterization of the mouse PA28 activator complex gene family: complete
      organizations of the three member genes and a physical map of the approximately
      150-kb region containing the alpha- and beta-subunit genes.
AB  - The proteasome is a multisubunit protease responsible for the generation of
      peptides loaded onto MHC class I molecules. Recent evidence indicates that
      binding of an IFN-gamma-inducible PA28 activator complex to the 20S proteasome
      enhances the generation of class I binding peptides. The alpha- and beta
      subunits, which constitute the PA28 activator complex in the form of an
      (alphabeta)3 heterohexamer, show significant amino acid sequence similarity to a
      protein, designated Ki or the gamma-subunit, that is capable of binding to the
      20S proteasome. In this study, we describe the complete nucleotide sequences of
      the mouse genes, Psme1, Psme2, and Psme3, coding for the alpha-, beta-, and gamma
      subunits, respectively. The overall exon-intron organizations of the three Psme
      genes are virtually identical, thus providing evidence that they are descended
      from a single ancestral gene. The promoter regions of the Psme1 and Psme2 genes
      contain sequence motifs that qualify as IFN-stimulated response elements,
      consistent with the observation that their expression is induced strongly by IFN
      gamma. The Psme1 and Psme2 genes are located approximately 6 kb apart with their
      3'-ends pointing toward each other on bands C2 to D1 of mouse chromosome 14,
      supporting the idea that they emerged by tandem duplication.

PMID- 9590242
TI  - The structure of avian CD5 implies a conserved function.
AB  - The chicken CD5 cDNA was isolated by COS cell expression cloning utilizing a
      novel mAb 2-191. The cDNA contains a 1422-nucleotide open reading frame encoding
      a mature protein with 32% and 30% identity to mouse and human CD5 polypeptides,
      respectively. The molecule consists of a 330-amino acid extracellular region with
      three repeats of the scavenger receptor cysteine-rich domain, a 29-amino acid
      hydrophobic transmembrane domain, and a 93-amino acid cytoplasmic tail. The
      cytoplasmic region contains motifs that are highly conserved between species,
      including several potential phosphorylation sites. The chicken CD5 is a 64-kDa
      phosphorylated glycoprotein with a protein core of 57 kDa as determined by
      immunoprecipitation and SDS-PAGE analysis. Alphabeta T cells express a
      homogeneously high level of CD5, whereas low or intermediate CD5 expression on
      gammadelta T cells depends on their tissue location. In contrast to human and
      mouse, CD5 is found at low levels on all chicken B cells. The high conservation
      of structural features, as well as signaling motifs, implies a conserved role for
      CD5 both in lymphocyte development and function.

PMID- 9590243
TI  - HLA-E surface expression depends on binding of TAP-dependent peptides derived
      from certain HLA class I signal sequences.
AB  - Previous studies showed that HLA-E was expressed in lymphoblastoid cell line
      (LCL) 721.221 cells, but surface expression was lacking. To determine the signals
      controlling surface expression, we constructed a series of hybrid genes using
      complementary portions derived from the HLA-E and HLA-A2 genes. In this manner, a
      hybrid of HLA-E was identified, designated AEH, which differed from HLA-E by
      having the HLA-A2 signal sequence substituting for the HLA-E leader peptide.
      Transfection of LCL 721.221 cells with AEH induced HLA-E surface expression.
      Analysis of peptides bound to HLA-E revealed that a nonamer peptide derived from
      the A2 signal sequence was the predominant peptide bound. LCL 721.221 cells
      transfected with certain class I genes, including HLA-G, were also sufficient to
      promote peptide binding and HLA-E surface expression without increasing the level
      of HLA-E heavy chain synthesis. Peptides bound to HLA-E consisted of nine amino
      acids, with methionine at position 2 and leucine in the carboxyl-terminal
      position, and were nearly identical to the leader sequence-derived peptide
      previously shown to be a predominant peptide bound to the murine Qa-1 Ag. Signal
      peptides derived from certain HLA-B proteins with threonine in position 2 only
      marginally up-regulated HLA-E surface expression in .221 cells. An examination of
      HLA-E peptide binding in the TAP negative cell line .134 indicated that peptide
      binding to HLA-E was dependent on a functional TAP heterodimer regardless of
      whether peptide was available in cis, as in the AEH construct, or in trans, as in
      the class I transfectants of .221 cells.

PMID- 9590244
TI  - Molecular mechanisms of inducible nitric oxide synthase gene expression by IL
      1beta and cAMP in rat mesangial cells.
AB  - Expression of the inducible nitric oxide synthase (iNOS) gene in rat mesangial
      cells is differentially triggered by IL-1beta and cAMP predominantly at the
      transcriptional level. The 5'-flanking region of the rat iNOS gene contains
      several binding sites for transcription factors potentially involved in cytokine
      and cAMP signaling such as nuclear factor-kappaB/Rel, CCAAT/enhancer-binding
      protein (C/EBP), and cyclic AMP-responsive element-binding protein/ATF. We tested
      promoter activities of serial and site-directed deletion mutants of iNOS
      chloramphenicol acetyltransferase reporter genes after transient transfection and
      stimulation of mesangial cells. A region between bp -277 and -111 bearing a
      CCAAT/enhancer-binding protein-response element was found to be critical for cAMP
      mediated gene induction but dispensable for IL-1beta inducibility. Moreover, a
      minimal promoter ranging from the transcriptional start site up to -111
      containing a kappaB site is sufficient to confer IL-1beta-mediated iNOS promoter
      activation. Consistent with these findings, an electrophoretic mobility shift
      assay shows the appearance of an IL-1beta-inducible nuclear factor-kappaB p50/p65
      heterodimeric complex. Using probes containing C/EBP-binding sites from the iNOS
      gene revealed further binding of different complexes, all of which were strongly
      inducible by cAMP and to a lower extent also by IL-1beta. Abs against cyclic AMP
      responsive element-binding protein, C/EBPbeta, and C/EBPdelta were able to
      partially supershift single complexes, suggesting the participation of these
      transcription factors in the regulation of iNOS gene expression by cAMP and IL
      1beta. Finally, we show that both cAMP and IL-1beta strongly induce steady-state
      levels of C/EBPbeta and C/EBPdelta mRNA levels. These data demonstrate that IL
      1beta and cAMP use distinct as well as partially overlapping sets of
      transcriptional activators to modulate iNOS gene expression in rat mesangial
      cells.

PMID- 9590245
TI  - Posttranscriptional lipopolysaccharide regulation of the lysozyme gene at
      processing of the primary transcript in myelomonocytic HD11 cells.
AB  - Lysozyme is increasingly expressed in macrophages in inflammatory response to
      bacterial LPS. In this study, we investigated the mechanisms that control
      expression of the lysozyme gene in myelomonocytic HD11 cells activated by LPS.
      Nuclear run-on transcription assays showed that LPS caused a 15-fold increase in
      the transcription rate of the lysozyme gene. However, Northern analyses with
      lysozyme cDNA and intron sequences revealed that the LPS-induced increase in
      nuclear lysozyme transcripts greatly exceeded the increase in transcription rate.
      Furthermore, nuclear lysozyme transcripts in untreated cells with a t(1/2) of <10
      min were more unstable than those accumulated in LPS-activated cells. We
      suggested, therefore, that the increased lysozyme expression following LPS
      treatment was largely due to a nuclear stabilization of the primary transcript.
      Interestingly, the increase in stability of the lysozyme primary transcript was
      accompanied by changes in nuclear processing including an increase in poly(A)
      tail length, which gradually shortened after entering the cytoplasm. The long
      lysozyme poly(A) tail, however, did not result in any increase in polysomal
      recruitment for translation or in stability of the cytoplasmic lysozyme mRNA.

PMID- 9590246
TI  - Phosphatidylinositol 3'-kinase and SH2-containing inositol phosphatase (SHIP) are
      recruited by distinct positive and negative growth-regulatory domains in the
      granulocyte colony-stimulating factor receptor.
AB  - Activation of both positive and "negative" or anti-proliferative signals has
      emerged as a common paradigm for regulation of cell growth through cell surface
      receptors that regulate immune responses. SHP-1 and -2 and the novel 5'-inositol
      phosphatase SHIP have recently been shown to function as growth inhibitory
      molecules in immune receptor signaling. In the current study, we have identified
      distinct regions in the granulocyte colony-stimulating factor receptor (G-CSFR)
      distal to the conserved box 2 motif necessary for mitogenesis, which exert
      positive and negative influences on growth signaling in Ba/F3 pro-B lymphoid
      cells. The region spanning amino acids 682 to 715 mediates activation of
      phosphatidylinositol 3'(PI3)-kinase. Activation of PI3-kinase leads to inhibition
      of apoptosis, promotion of cell survival, and enhanced proliferative responses to
      G-CSF. We show that the region of 98 amino acids in the distal tail of the class
      I G-CSFR down-modulates proliferative signaling, not only in myeloid cell lines,
      as previously reported, but also in Ba/F3 cells. This same region recruits SHIP
      to the signaling cascade through a mechanism involving Shc, with the formation of
      Shc/SHIP complexes. Our data suggest a model in which PI3-kinase and SHIP
      coordinately regulate growth signaling through the G-CSFR.

PMID- 9590247
TI  - Purification and characterization of lymphocyte chymase I, a granzyme implicated
      in perforin-mediated lysis.
AB  - One mechanism of killing by cytotoxic lymphocytes involves the exocytosis of
      specialized granules. The released granules contain perforin, which assembles
      into pores in the membranes of cells targeted for death. Serine proteases termed
      granzymes are present in the cytotoxic granules and include several chymases
      (with chymotrypsin-like specificity of cleavage). One chymase is selectively
      reactive with an inhibitor, Biotinyl-Aca-Aca-Phe-Leu-PheP(OPh)2, that blocks
      perforin lysis. We report the purification and characterization of this chymase,
      lymphocyte chymase I, from rat natural killer cell (RNK)-16 granules. Lymphocyte
      chymase I is 30 kDa with a pH 7.5 to 9 optimum and primary substrate preference
      for tryptophan, a preference distinct from rat mast cell chymases. This chymase
      also reacts with other selective serine protease inhibitors that block perforin
      pore formation. It elutes by Cu2+-immobilized metal affinity chromatography with
      other granzymes and has the N-terminal protein sequence conserved among
      granzymes. Chymase I reduces pore formation when preincubated with perforin at 37
      degrees C. In contrast, addition of the chymase without preincubation had little
      effect on lysis. It should be noted that the perforin preparation contained
      sufficient residual chymase activity to support lysis. Thus, the reduction of
      lysis may represent an effect of excess prolytic chymase I or a means to limit
      perforin lysis of bystander cells. In contrast, other chymases and granzyme K
      were without effect when added to perforin during similar preincubation.
      Identification of the natural substrate of chymase I will help resolve how it
      regulates perforin-mediated pore formation.

PMID- 9590248
TI  - Localization and regulation of IFN-gamma production within the granulomas of
      murine schistosomiasis in IL-4-deficient and control mice.
AB  - Schistosome granulomas from normal or IL-4-deficient C57BL/6 mice make little IFN
      gamma and show no Th1 polarization. This could signify that these granulomas have
      few cells capable of IFN-gamma synthesis or that such cells are under tight
      control. Granulomas can make IL-10 and TGF-beta, which can regulate IFN-gamma
      synthesis. Using FACS analysis and ELISA, we explored the origin and regulation
      of IFN-gamma in schistosome granulomas from both IL-4(-/-) and IL-4(+/+) mice.
      FACS analysis of intracytoplasmic IFN-gamma staining showed that some granuloma
      Thy1.2+ T cells (CD8+ and CD4+) express IFN-gamma. Granulomas had NK1.1+ cells,
      but they appeared to produce little or no IFN-gamma. Purified granuloma Thy1.2+
      cells made IFN-gamma in vitro, whereas isolated NK1.1+ lymphocytes secreted
      little even with rIL-12 stimulation. Culture of granuloma cells with blocking
      anti-IL-10 or anti-TGF-beta mAb or with rIL-12 substantially increased T cell IFN
      gamma synthesis, particularly in the IL-4(-/-) animals. Cultured granuloma cells
      depleted of Thy1.2+ lymphocytes by Ab and C released no IFN-gamma. It is
      concluded that granuloma IFN-gamma comes from T cells, not NK cells. Also, this T
      cell-derived IFN-gamma is subject to IL-10 and TGF-beta regulation, which is
      particularly evident in IL-4(-/-) mice. Thus, the Th2 granuloma of
      schistosomiasis has large numbers of activated Th1 or Th0 lymphocytes that are
      under tight restraint.

PMID- 9590249
TI  - Cellular mechanism of intraabdominal abscess formation by Bacteroides fragilis.
AB  - We investigated the cellular mechanism by which Bacteroides fragilis promotes the
      development of intraabdominal abscesses in experimental models of sepsis. B.
      fragilis, as well as purified capsular polysaccharide complex (CPC) from this
      organism, adhered to primary murine mesothelial cells (MMCs) in vitro. The
      binding of CPC to murine peritoneal macrophage stimulated TNF-alpha production,
      which when transferred to monolayers of MMCs elicited significant ICAM-1
      expression by these cells. This response resulted in enhanced polymorphonuclear
      leukocyte attachment to MMCs that could be inhibited by Abs specific for TNF
      alpha or ICAM-1. Mice treated with TNF-alpha- or ICAM-1-specific Abs failed to
      develop intraabdominal abscesses following challenge with purified CPC. These
      results illustrated the role of the CPC in promoting adhesion of B. fragilis to
      the peritoneal wall and coordinating the cellular events leading to the
      development of abscesses associated with experimental intraabdominal sepsis.

PMID- 9590250
TI  - CD4+ and CD8+ T cell interactions in IFN-gamma and IL-4 responses to viral
      infections: requirements for IL-2.
AB  - Cytokine responses to lymphocytic choriomeningitis virus infections were
      evaluated, and CD8+ T cell, CD4+ T cell, and IL-2 contributions delineated. In
      immunocompetent mice, lymphocytic choriomeningitis virus induced both IFN-gamma
      and IL-4 as well as IL-2. Experiments in mice either beta2-microglobulin
      deficient, lacking MHC class I molecules and CD8+ T cells, or A beta(b)
      deficient, lacking MHC class II molecules and CD4+ T cells, demonstrated that
      mixtures of T cell responses were required for optimal ex vivo cytokine
      productions. Intracellular cytokine expression analyses of cells from
      immunocompetent and immunodeficient mice showed that CD8+ T cells were
      predominant IFN-gamma producers, and that expansion of CD8+ T cells primed to
      make IFN-gamma was independent of CD4+ T cells in vivo. Studies in IL-2-deficient
      mice demonstrated that this cytokine promoted IFN-gamma and IL-4 responses, and
      ex vivo experiments showed that exogenous IL-2 was required to maintain high
      level IFN-gamma production by in vivo-primed CD8+ T cells. Conditions associated
      with cytokine decreases were accompanied by reduced detectable plasma Ab
      responses. The results indicate that, although IL-2-dependent CD8+ T cell
      proliferation does not require endogenous CD4+ T cells, IL-2 production by the
      CD4+ T cells may promote continued cytokine release from activated CD8+ T cells.
      By defining these critical steps in cellular and cytokine interactions for
      shaping endogenous immune responses, the studies advance understanding of the
      unique conditions regulating CD8+ T cell responses to viral challenges.

PMID- 9590251
TI  - CBL-GRB2 interaction in myeloid immunoreceptor tyrosine activation motif
      signaling.
AB  - In this study, we provide the first evidence for role of the CBL adapter protein
      interaction in Fc gammaRI receptor signal transduction. We study the Fc gammaRI
      receptor, an immunoreceptor tyrosine activation motif (ITAM)-linked signaling
      pathway, using IFN-gamma-differentiated U937 myeloid cells, termed U937IF cells.
      CBL is constitutively associated with both GRB2 and the ITAM-containing receptor
      subunit, Fc gammaRIgamma of Fc gammaRI, providing direct evidence that CBL
      functions in myeloid ITAM signaling. Fc gammaRI cross-linking of U937IF cells
      induces the tyrosine phosphorylation of CBL that is associated with an altered
      CBL-GRB2 interaction. Both GRB2-SH3 and SH2 domains bind CBL in resting cell
      lysates; upon Fc gammaRI stimulation, phosphorylated CBL binds exclusively to the
      GRB2-SH2 domain. Glutathione-S-transferase fusion protein data demonstrate that
      the constitutive interaction of CBL with GRB2 and CRKL is mediated via two
      discrete regions of the CBL C terminus. The proximal C terminus (residues 461
      670) binds to GRB2 constitutively, and under conditions of receptor activation
      binds to the tyrosine-phosphorylated SHC adapter molecule. The distal C terminus
      of CBL (residues 671-906) binds the CRKL adapter protein. The data demonstrate
      that the CBL-GRB2 and GRB2-SOS protein complexes are distinct and mutually
      exclusive in U937IF cells, supporting a model by which the CBL-GRB2 and GRB2-SOS
      complexes function in separate pathways for myeloid Fc gammaRI signaling.

PMID- 9590252
TI  - Bactericidal monoclonal antibodies that define unique meningococcal B
      polysaccharide epitopes that do not cross-react with human polysialic acid.
AB  - The poor immunogenicity of the Neisseria meningitidis group B polysaccharide
      capsule, a homopolymer of alpha(2-->8) sialic acid, has been attributed to
      immunologic tolerance induced by prenatal exposure to host polysialyated
      glycoproteins. Substitution of N-propionyl (N-Pr) for N-acetyl groups on the
      meningococcal B polysaccharide, and conjugation of the resulting polysaccharide
      to a protein carrier, have been reported to yield a conjugate vaccine that
      elicits protective Abs with minimal autoantibody activity. To characterize the
      protective epitopes on the derivatized polysaccharide, we isolated 30 anti-N-Pr
      meningococcal B polysaccharide mAbs. These Abs were heterogeneous with respect to
      complement-mediated bactericidal activity, fine antigenic specificity, and
      autoantibody activity as defined by binding to the neuroblastoma cell line, CHP
      134, which expresses long-chain a(2-->8)-linked polysialic acid. Eighteen of the
      Abs could activate complement-mediated bacteriolysis. Seven of these 18 Abs cross
      reacted with N-acetyl meningococcal B polysaccharide by ELISA and had strong
      autoantibody activity. Thus, N-Pr meningococcal B polysaccharide conjugate
      vaccine has the potential to elicit autoantibodies. However, 7 of the 18
      bactericidal mAbs had no detectable autoantibody activity. These Abs may be
      useful for the identification of molecular mimetics capable of eliciting
      protective Abs specific to the bacteria, without the risk of evoking autoimmune
      disease.

PMID- 9590253
TI  - FTY720, a novel immunosuppressant, induces sequestration of circulating mature
      lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively
      decreases the number of circulating mature lymphocytes by acceleration of
      lymphocyte homing.
AB  - FTY720, given i.v. or orally at 0.03 mg/kg or more, significantly prolonged skin
      allograft survival in a dose-dependent manner and showed more potent
      immunosuppressive activity than cyclosporin A (CsA) or tacrolimus (FK506) in MHC
      incompatible rat strains of WKAH donors and F344 recipients. However, unlike CsA
      or FK506, FTY720 up to 1000 nM did not affect IL-2 production in allogeneic MLC.
      Within 3 to 24 h after a single oral administration of FTY720 at 0.1 to 1 mg/kg,
      the number of lymphocytes in the rats was markedly decreased in the peripheral
      blood and thoracic duct lymph and partially in spleen. By contrast, the number of
      lymphocytes in peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN), and
      Peyer's patches (PP) was significantly increased at the same time. Intravenous
      transfusion of calcein-labeled rat lymphocytes into rats revealed that FTY720
      significantly accelerated lymphocyte homing to PLN, MLN, and PP, dose
      dependently. Since FTY720-induced lymphocyte homing was completely blocked by
      simultaneous treatment of the calcein-labeled lymphocytes with mAbs against
      CD62L, CD49d, and CD11a before the transfusion, the acceleration of lymphocyte
      homing by FTY720 appears to be mediated by lymphocyte-homing receptors. These
      findings indicate that FTY720 sequesters circulating mature lymphocytes into PLN,
      MLN, and PP by acceleration of lymphocyte homing and thereby decreases the number
      of lymphocytes in peripheral blood, thoracic duct lymph, and spleen. Based on
      these observations, sequestration of circulating mature-lymphocytes is presumed
      to be a main mechanism of the immunosuppressive activity of FTY720.

PMID- 9590254
TI  - B7 costimulatory requirements of T cells at an inflammatory site.
AB  - The requirement for T cell costimulation at sites of infection and inflammation
      is unresolved. Herpes stromal keratitis (HSK) is a CD4+ T cell-regulated
      inflammatory response to herpes simplex virus type 1 infection of the cornea. Our
      findings suggest that susceptibility to HSK is determined by the microenvironment
      of the infected cornea. The cornea is normally devoid of Langerhans cells (LC),
      but these APC are present in the surrounding conjunctiva, and migrate into the
      cornea following infection. The costimulatory molecule B7-2 was constitutively
      expressed on LC in conjunctiva, but B7-1 was not detectable until 3 days
      postinfection. LC were the only cells in the cornea that expressed B7-1 through 7
      days postinfection. B7-1 was expressed on some, but not all, migrating LC,
      suggesting that LC migration and B7-1 expression can be independently regulated.
      The early LC migration and B7-1 expression was independent of T cells, but T
      cells were required for the massive accumulation of B7-1+ LC in the cornea at the
      onset of inflammation. Local inhibition of B7-1 function within the infected
      cornea prevented HSK. Locally blocking B7-2 function did not reduce HSK
      incidence, but markedly reduce HSK severity. This is the first direct
      demonstration that naturally expressed B7 is required within an inflammatory
      site.

PMID- 9590255
TI  - Human mast cells augment fibroblast proliferation by heterotypic cell-cell
      adhesion and action of IL-4.
AB  - Mast cells have been implicated in the pathogenesis of fibrosis because of their
      increased number in chronic inflammatory reactions. In a previous study, we had
      shown that human mast cells readily attach and form heterotypic cell-cell
      contacts when seeded on top of fibroblast monolayers. Here, we report that human
      mast cells stimulate fibroblast proliferation after cell-cell contact.
      Proliferation was measured by 5-bromo-2'-deoxyuridine or [3H]thymidine uptake of
      subconfluent fibroblast monolayers after attachment of mast cells that had been
      preincubated with mitomycin C. An 18-h coculture of the human mast cell line HMC
      1 doubled proliferation of normal skin fibroblasts. Moreover, normal mast cells
      prepared from neonatal foreskin doubled fibroblast proliferation. The stimulatory
      effect was dependent on heterotypic cell-cell contact since it was not
      transferred by tissue culture supernatants from mast cells. We hypothesized that
      mast cell cytokines secreted after heterotypic cell-cell contact stimulate
      fibroblast proliferation. Several mast cell-derived cytokines were tested for
      effects on fibroblast proliferation. Only IL-4 was able to double fibroblast
      proliferation. Additional experiments revealed that: 1) the stimulatory effect of
      IL-4 as well as of the mast cell coculture could be completely abrogated by
      preincubation of fibroblasts with an anti-IL-4R mAb blocking ligand binding; 2)
      mast cell-derived IL-4 acts as a second signal for fibroblasts since it amplifies
      the action of low doses of obligatory fibroblast growth factors such as
      fibroblast growth factor or platelet-derived growth factor.

PMID- 9590256
TI  - Functional mapping of CD11b/CD18 epitopes important in neutrophil-epithelial
      interactions: a central role of the I domain.
AB  - In the intestine, lung, and urinary tract, neutrophil (polymorphonuclear
      leukocyte, PMN) transepithelial migration is dependent on the leukocyte beta2
      integrin CD11b/CD18. While the regions of CD11b involved in recognition of
      several soluble ligands are known, those that mediate PMN-epithelial interactions
      have not been investigated. In this study, mAbs reactive with four extracellular
      regions on CD11b, the NH2-terminal region, I (inserted) domain, cation-binding
      region, and region proximal to the transmembrane domain (C domain), were analyzed
      for the ability to block CD11b/CD18-mediated interactions with T84 intestinal
      epithelial cells. In such a manner, epitope mapping was applied to the complex
      interactions between CD11b/CD18 and a cell-based ligand system. I domain Abs
      strongly inhibited both adhesion of PMN to epithelial cells and PMN migration
      across T84 epithelial monolayers. However, the profile of inhibition was distinct
      from that of other known ligands of CD11b/CD18. CBRM1/32, an Ab to a
      discontinuous epitope residing within the NH2- and cation-binding domains,
      strongly inhibited both adhesion and transmigration responses. C domain Abs had
      minimal effects on adhesion and transmigration. These findings appear applicable
      to other epithelia, since similar results were obtained in transmigration
      experiments with CF15 human airway epithelial cells. Finally, Ab inhibition
      profiles were confirmed with adhesion assays of isolated epithelial cells to
      purified CD11b/CD18. These findings demonstrate the central role of the I domain
      and the participation of a discontinuous region shared by the NH2- and cation
      binding domains in mediating PMN-adhesive interactions with epithelial cells.

PMID- 9590257
TI  - Synergistic effect of type II phospholipase A2 and platelet-activating factor on
      Mac-1 surface expression and exocytosis of gelatinase granules in human
      neutrophils: evidence for the 5-lipoxygenase-dependent mechanism.
AB  - Stimulation of human neutrophils with inflammatory mediators such as TNF-alpha or
      platelet-activating factor (PAF) induces translocation of adhesion molecule Mac-1
      (CD11b/CD18) from secretory vesicles to the plasma membrane. Type II
      phospholipase A2 (PLA2-II) also induces translocation of Mac-1 from secretory
      vesicles. However, there are more Mac-1 molecules in gelatinase granules and
      specific granules than in secretory vesicles. Therefore, different combinations
      of PLA2-II and other mediators were examined for their ability to induce
      gelatinase granules and specific granules to induce Mac-1 surface expression. The
      combination of PLA2-II and PAF synergistically increased Mac-1 surface
      expression, and the effect was greater than the combinations of PLA2-II with TNF
      alpha, IL-8, or FMLP. Additionally, the combination of PLA2-II and PAF induced
      exocytosis of both secretory vesicles and gelatinase granules, which did not
      occur with either PLA2-II alone or PAF alone. The induction was accompanied by
      marked production of leukotriene B4. AA861, an inhibitor of 5-lipoxygenase, did
      not inhibit exocytosis of secretory vesicles but did inhibit exocytosis of
      gelatinase granules and decrease Mac-1 surface expression. It was also found that
      Ca2+ influx is essential for 5-lipoxygenase activation, because Ni2+, which
      blocks the influx of extracellular Ca2+, inhibited the production of leukotriene
      B4. These results suggest that stimulation by the combination of PLA2-II and PAF,
      unlike stimulation by each mediator alone, causes exocytosis of gelatinase
      granules via the 5-lipoxygenase pathway, resulting in a synergistic increase in
      neutrophil Mac-1 surface expression during inflammatory processes.

PMID- 9590258
TI  - Expression of receptors for C5a anaphylatoxin (CD88) on human bronchial
      epithelial cells: enhancement of C5a-mediated release of IL-8 upon exposure to
      cigarette smoke.
AB  - Results are presented that demonstrate a heightened responsiveness of human
      bronchial epithelial cells (HBECs) toward the complement-derived anaphylatoxin
      C5a when these cells are exposed to cigarette smoke. This C5a response is
      possible because we show at both the protein and mRNA levels that HBECs
      constitutively express receptors for C5a (C5aR, CD88). Control (untreated) HBECs
      responded to C5a (50 nM) by releasing the proinflammatory cytokine IL-8 at low
      but significant levels. However, exposure of HBECs to 5% cigarette smoke extract
      (CSE) for at least 15 min resulted in an increase in the ability of an anti-human
      C5aR Ab to bind to the cell surface. CSE-treated HBECs responded in a dose
      dependent fashion to human recombinant C5a and to a conformationally biased
      decapeptide agonist of C5a (YSFKPMPLaR) by releasing IL-8. The levels of IL-8
      released in response to C5a were significantly greater in CSE-treated HBECs than
      in control HBECs. Moreover, this C5a-mediated release of IL-8 from CSE-treated
      HBECs was significantly reduced in the presence of the anti-human C5aR Ab. These
      results indicate that HBECs constitutively express C5aRs and that exposure to
      environmental irritants such as cigarette smoke modulates the expression and
      responsiveness of these C5aRs toward the C5a-mediated release of IL-8.

PMID- 9590259
TI  - Staphylococcus aureus-induced septic arthritis and septic death is decreased in
      IL-4-deficient mice: role of IL-4 as promoter for bacterial growth.
AB  - Lack of IL-4 has been shown to be protective in some experimental models of
      infectious diseases in mice such as cutaneous leishmaniasis. At the same time IL
      4, together with other Th2 cytokines, including IL-10 and IL-13, is known as an
      anti-inflammatory cytokine with the potential to down-regulate proinflammatory
      cytokine production. To investigate the role of IL-4 in experimental
      Staphylococcus aureus-induced and T lymphocyte-mediated arthritis, IL-4-deficient
      C57BL/6 mice (IL-4(-/-)) and their congenic controls (IL-4(+/+)) were inoculated
      with a toxic shock syndrome toxin-1-producing S. aureus strain. In IL-4(+/+)
      mice, arthritis peaked 14 days after bacterial inoculation, whereas, at that
      time, IL-4(-/-) mice displayed significantly less frequent (p < 0.05) joint
      inflammation. Paralleling lower frequency of arthritis, IL-4-deficient mice
      showed a decreased bacterial burden in joints (p = 0.014) and kidneys (p =
      0.029), as well as lower infection-triggered weight decrease and mortality. In
      vitro, IL-4 inhibited intracellular killing of S. aureus in infected macrophages,
      without affecting phagocytosis. This finding may explain the enhanced
      staphylococcal clearance observed in IL-4(-/-) mice in vivo. Our results suggest
      that IL-4 and IL-4-dependent Th2 responses promote septic arthritis and sepsis
      related mortality by inhibition of bacterial clearance during S. aureus
      infection.

PMID- 9590260
TI  - Escherichia coli bound to the primate erythrocyte complement receptor via
      bispecific monoclonal antibodies are transferred to and phagocytosed by human
      monocytes in an in vitro model.
AB  - We have prepared cross-linked, bispecific mAb complexes (heteropolymers) that
      facilitate rapid and quantitative binding of a prototype pathogen, Escherichia
      coli, to the complement receptor (CR1) on primate erythrocytes. Incubation of the
      erythrocyte-heteropolymer-E. coli complexes with freshly isolated human
      mononuclear cells leads to rapid removal of the E. coli from the erythrocytes,
      and phagocytosis and killing of the bacteria. The erythrocytes are not lysed or
      phagocytosed during this transfer reaction, but both heteropolymer and CR1 are
      removed from the erythrocytes along with the E. coli. These findings parallel
      observations made in previous in vivo experiments in which heteropolymers were
      used to facilitate clearance of innocuous prototype pathogens in a monkey model.
      It should now be possible to extend the heteropolymer paradigm to a live pathogen
      in a primate model.

PMID- 9590261
TI  - Regulation of TNF-alpha production in activated mouse macrophages by
      progesterone.
AB  - The purpose of this study was to investigate the relationships between macrophage
      production of TNF-alpha and female hormones. Northern blot hybridization
      experiments showed that the female sex steroid hormone, progesterone, decreases
      steady state levels of TNF-alpha mRNA in LPS-activated mouse macrophages (RAW
      264.7 and ANA-1 cells) in vitro. The production of intracellular and secreted TNF
      alpha protein, as determined by ELISA, was decreased in both progesterone- and
      dexamethasone-treated, LPS-stimulated macrophages. Estrogen had no effect on
      expression of the TNF-alpha gene in mouse macrophages and did not alter
      progesterone-mediated suppression. Additional experiments conducted to
      investigate the mechanism of action of progesterone showed that this hormone,
      like dexamethasone, elevates steady state mRNA levels of IkappaB alpha and
      increases the levels of IkappaB alpha protein that are translocated from the
      cytoplasm to the nucleus. Thus, progesterone is a potent inhibitor of steady
      state levels TNF-alpha mRNA and TNF-alpha protein production in activated
      macrophages and may achieve this result through effects on an inhibitor of NF
      kappaB.

PMID- 9590262
TI  - IFN-gamma-deficient mice develop severe granulomatous experimental autoimmune
      thyroiditis with eosinophil infiltration in thyroids.
AB  - To study the role of IFN-gamma in the development of granulomatous experimental
      autoimmune thyroiditis (EAT), DBA1 mice with a disrupted IFN-gamma gene were used
      for adoptive EAT induction. Effector cells from either IFN-gamma(+/+) or IFN
      gamma(-/-) donor mice activated with mouse thyroglobulin and anti-IL-2R mAb
      induced severe granulomatous EAT. A predominant infiltration of the thyroid by
      eosinophils was observed in recipients of IFN-gamma(-/-) effector cells but not
      in recipients of IFN-gamma(+/+) cells. Compared with wild-type mice, thyroids of
      recipients of IFN-gamma(-/-) effector cells had decreased expression of mRNA for
      Th1 cytokines and inducible nitric oxide synthetase. Expression of Th2 cytokine
      mRNA was comparable to that of IFN-gamma(+/+) mice, and expression of eotaxin was
      increased in the thyroids of recipients of IFN-gamma(-/-) effector cells.
      Activation of cells from either IFN-gamma(+/+) or IFN-gamma(-/-) donors in the
      presence of IL-12 also induced severe granulomatous EAT. Eosinophil infiltration
      in recipients of IFN-gamma(-/-) cells was unaffected when effector cells were
      activated with IL-12, and thyroids expressed predominantly Th2 cytokines. The
      extent of fibrosis of recipient thyroids was generally greater when donor IFN
      gamma(+/+) and IFN-gamma(-/-) cells were activated with IL-12. Compared with IFN
      gamma(+/+) mice, IFN-gamma(-/-) mice produced lower levels of mouse thyroglobulin
      specific autoantibodies after immunization with MTg and LPS. These results
      indicate that cells from both IFN-gamma(+/+) and IFN-gamma(-/-) donors can induce
      severe granulomatous EAT. However, damage of thyroid follicles by IFN-gamma(-/-)
      and that by IFN-gamma(+/+) cells appear to involve different mediators of
      inflammation.

PMID- 9590263
TI  - Intrinsic differences in L-selectin expression levels affect T and B lymphocyte
      subset-specific recirculation pathways.
AB  - Lymphocyte migration into lymphoid organs is regulated by tissue-specific
      adhesion molecules such as L-selectin and the alpha4beta7 integrin. Whether L
      selectin also regulates lymphocyte subset-specific migration into specific
      lymphoid tissues was examined in this study by comparing the migration of CD4+ T
      cells, CD8+ T cells, and B cells from L-selectin-deficient and wild-type mice. T
      cells were the predominant lymphocyte subset entering PLN, MLN, Peyer's patches,
      and spleen during short term (1-h) migration assays. However, both B cell and
      CD4+ and CD8+ T cell entries into PLN, MLN, and Peyer's patches were dramatically
      impaired (73-98%) by loss of L-selectin. Lymphocyte expression of alpha4beta7
      integrin did not compensate for the loss of L-selectin, since both B and T cells
      predominantly migrated into the spleen in the absence of L-selectin. The more
      efficient migration of T cells into peripheral lymphoid tissues relative to that
      of B cells was partly explained by the finding that T cells expressed L-selectin
      at 50 to 100% higher levels than B cells. In addition, a 50% reduction in L
      selectin expression by lymphocytes from hemizygous L-selectin(+/-) mice resulted
      in a 50 to 70% decrease in short term lymphocyte migration into peripheral
      lymphoid tissues relative to that of wild-type lymphocytes. Thus, the
      differential migration of T and B lymphocyte subsets to lymphoid tissues is
      regulated in part by subset-specific differences in L-selectin expression levels.

PMID- 9590264
TI  - An sLex-deficient variant of HL60 cells exhibits high levels of adhesion to
      vascular selectins: further evidence that HECA-452 and CSLEX1 monoclonal antibody
      epitopes are not essential for high avidity binding to vascular selectins.
AB  - Selectins are carbohydrate-binding cell adhesion molecules that play a key role
      in the initiation of inflammatory responses. Several studies have suggested that
      the sialylated, fucosylated tetrasaccharide sialyl Lewis X (sLex) is an important
      component of leukocyte ligands for E- and P-selectin. We have identified a stable
      variant of the HL60 cell line, HL60var, which displays a nearly complete absence
      of staining with several mAb directed against sLex and/or sLex-related
      structures. HL60var also exhibits a concomitant increase in reactivity with mAb
      directed against the unsialylated Lewis X (Lex/CD15) structure. Despite this sLex
      deficiency, HL60var binds well to both E- and P-selectin. No significant
      differences in expression of alpha1,3-fucosyltransferases, C2GnT (Core2
      transferase), or P-selectin glycoprotein ligand-1 between HL60var and typical
      sLex(high) HL60 cells were detected. Although the precise molecular basis for the
      sLex(-/low) phenotype of HL60var remains uncertain, flow cytometric analysis with
      the sialic acid-specific Limax flavus lectin revealed a sharp reduction in
      HL60var surface sialylation. Thus, the loss in mAb reactivity may result from a
      loss of sialic acid residues from the mAb carbohydrate epitope. However, binding
      of HL60var to E- and P-selectin remains sensitive to neuraminidase treatment.
      Taken together, these data indicate that high levels of surface sLex and/or
      related epitopes are not essential for interactions with vascular selectins,
      implying that as yet unidentified sialylated, fucosylated structures serve as
      physiologically relevant ligands for E- and P-selectin.

PMID- 9590265
TI  - Potential mechanisms for a proinflammatory vascular cytokine response to
      coagulation activation.
AB  - We have previously shown that an anticoagulant could attenuate inflammation in
      animal models of sepsis with disseminated intravascular coagulation (DIC) and
      that coagulation activation of human whole blood ex vivo results in a
      proinflammatory cytokine response. The current studies were performed to better
      understand mechanisms for the blood cell cytokine response and extend the
      investigation of such a response to endothelial cells as likely contributors to a
      vascular inflammatory response. Utilizing cell separation techniques, it was
      determined that the whole blood IL-8 response to coagulation activation or
      thrombin, specifically, was mediated by CD14+ monocytes. Moreover, thrombin was
      observed to stimulate both IL-8 and IL-6 production in cultured mononuclear
      cells. Analyses of the effects of coagulation activation and thrombin were
      extended to cultured human endothelial cells, and a similar cytokine response was
      observed. Thrombin catalytic activity appeared essential, since hirudin reduced
      thrombin-stimulated proinflammatory cytokine production in cultured monocytes and
      endothelial cells and prothrombin only weakly mimicked the thrombin response. The
      endothelial cell IL-8 and IL-6 response to thrombin could be mimicked by the
      thrombin receptor agonist peptide (TRAP), implicating a functional role of the
      classic thrombin receptor. Altogether, the results facilitate a better
      understanding of potential proinflammatory vascular responses to coagulation
      activation.

PMID- 9590266
TI  - Quercetin sensitizes RBL-2H3 cells to polybasic mast cell secretagogues through
      increased expression of Gi GTP-binding proteins linked to a phospholipase C
      signaling pathway.
AB  - Polybasic secretagogues such as mastoparan, compound 48/80, substance P, and
      somatostatin stimulate secretion in rat peritoneal mast cells through direct
      activation of the heterotrimeric G protein, G(i-3). Cultured RBL-2H3 mast cells
      do not normally respond to these secretagogues, but, as reported here, they do so
      after prolonged exposure to the kinase inhibitor, quercetin. This inhibitor,
      which causes phenotypic changes in RBL-2H3 cells, induces a substantial increase
      (more than sevenfold) in the expression of alpha subunits of the pertussis toxin
      sensitive G proteins, G(i-2) and G(i-3). Compound 48/80-induced secretion is
      associated with transient hydrolysis of phosphoinositides and a transient
      increase in cytosolic calcium ions. These responses are inhibited by pertussis
      toxin, and in addition, secretion is blocked by calcium chelation and the protein
      kinase C inhibitor, Ro31-7549. These results delineate a pathway for compound
      48/80-induced secretion in mast cells via Gi protein(s), phospholipase C,
      calcium, and protein kinase C. The results also imply that phospholipase C, most
      likely phospholipase Cbeta3, can be transiently activated in RBL-2H3 cells by
      subunits of Gi proteins to induce cellular responses.

PMID- 9590267
TI  - IFN-gamma is produced by polymorphonuclear neutrophils in human uterine
      endometrium and by cultured peripheral blood polymorphonuclear neutrophils.
AB  - Cytokines present in the human uterus play an important role both in modulating
      immune responses to infectious challenge and in the establishment and maintenance
      of pregnancy. In particular, successful implantation and pregnancy is thought to
      require the establishment of a Th2 environment, while Th1 cytokines are
      associated with pregnancy loss and infertility. On the other hand, a Th1 response
      appears to be required for the resolution of acute infection. Using novel
      confocal microscopic analysis of fresh sections of human tissue, we have
      investigated the production of IFN-gamma, a Th1 cytokine, in human endometria.
      Extracellular IFN-gamma, mostly associated with matrix components, was located
      immediately beneath the luminal epithelium and along the glandular epithelium
      proximal to the lumen. As evidenced by intracellular staining, IFN-gamma is
      produced by both stromal cells and intraepithelial lymphocytes through all stages
      of the menstrual cycle. Surprisingly, the stromal cell containing intracellular
      IFN-gamma was identified as a polymorphonuclear neutrophil on the basis of its
      reactivity with a panel of mAbs and its nuclear morphology. We further found that
      polymorphonuclear neutrophils isolated from normal donors produce IFN-gamma in
      response to stimulation with LPS, IL-12, and TNF-alpha. Taken together, these
      findings suggest that polymorphonuclear neutrophils are capable of producing IFN
      gamma both in vitro and in vivo, indicating that their role in shaping immune
      responses may be more extensive than previously thought. Furthermore, these
      studies strongly suggest that polymorphonuclear neutrophils play an important
      role in determining immune responsiveness within the female reproductive tract.

PMID- 9590269
TI  - TGF-beta1 as an endogenous defender against macrophage-triggered stromelysin gene
      expression in the glomerulus.
AB  - Recent investigation has indicated that TGF-beta1, the macrophage (Mphi)
      deactivator, may attenuate Mphi-mediated acute glomerular injury. Using
      stromelysin as an indicator, this study investigated whether and how endogenous
      TGF-beta1 modulates the glomerular cell activation triggered by Mphi. Rat
      mesangial cells were stably transfected with a cDNA encoding the active form of
      TGF-beta1 and a cDNA coding for a dominant-negative mutant of the TGF-betaR type
      II. Compared with mock-transfected cells, TGF-beta1 transfectants exhibited
      blunted expression of stromelysin in response to the Mphi-derived, inflammatory
      cytokine IL-1beta. In contrast, mesangial cells expressing the dominant
      interfering TGF-betaR showed enhanced expression of stromelysin in response to IL
      1beta, suggesting that endogenous TGF-beta functions as an autocrine inhibitor of
      the IL-1 response. In isolated, normal rat glomeruli, externally added TGF-beta1
      suppressed the induction of stromelysin by mediators that were elaborated by
      activated Mphi. Similarly, when isolated, nephritic glomeruli producing the
      active form of TGF-beta1 were stimulated by IL-1beta or Mphi-conditioned medium,
      the induction of stromelysin was dramatically suppressed as compared with normal
      glomeruli. To investigate whether endogenous TGF-beta1 affects the glomerular
      cell activation triggered by Mphi, a technique for adoptive Mphi transfer was
      used. LPS-stimulated reporter Mphi were transferred into either normal rat
      glomeruli or nephritic glomeruli expressing active TGF-beta1. In the normal
      glomeruli, stromelysin expression was markedly induced in resident cells after
      the transfer of activated Mphi. This induction was substantially repressed in
      those glomeruli producing active TGF-beta1. These results reinforce the idea that
      TGF-beta1 is an endogenous defender that attenuates certain actions of
      infiltrating Mphi in the glomerulus.

PMID- 9590268
TI  - Syk activation is required for spreading and H2O2 release in adherent human
      neutrophils.
AB  - Chemoattractant-stimulated polymorphonuclear leukocytes (PMNs) that are adherent
      to extracellular matrix proteins exhibit a massive, sustained respiratory burst
      that requires cell spreading. However, the signaling pathways culminating in PMN
      spreading are not well characterized. Studies showing that protein tyrosine
      phosphorylation increases with PMN spreading suggest that phosphorylation is
      critical for this process. In the present study, we observed increased tyrosine
      phosphorylation of both focal adhesion kinase and Syk in FMLP-activated PMNs that
      had been plated onto fibrinogen; an increase in Syk activity, but not focal
      adhesion kinase activity, was apparent. The time course of Syk phosphorylation
      correlated with the initiation of cell spreading and H2O2 release. Pretreatment
      of PMNs with piceatannol, a Syk-selective inhibitor, blocked Syk activity, cell
      spreading, and H2O2 release, indicating that Syk activity was required for the
      activation of adherent PMNs. Paxillin is a cytoskeletally associated protein that
      is also tyrosine phosphorylated during PMN spreading and H2O2 release. Paxillin
      phosphorylation is kinetically slower than Syk phosphorylation and is inhibited
      with piceatannol, suggesting that paxillin is a substrate for Syk. An analysis of
      Syk immunoprecipitates indicated that Syk and paxillin associate during PMN
      spreading. This interaction is not mediated by the src kinases Lyn and Fgr, since
      neither kinase coprecipitated with Syk. Syk from FMLP-activated, adherent PMNs
      phosphorylated paxillin-glutathione S-transferase, suggesting that paxillin is a
      substrate for Syk in vivo. These results indicate that PMN spreading and H2O2
      release require a Syk-dependent signaling pathway leading to paxillin
      phosphorylation.

PMID- 9590270
TI  - In vivo effects of a bacterial superantigen on macaque TCR repertoires.
AB  - A macaque model was employed to explore staphylococcal enterotoxin B (SEB)
      superantigen-driven T lymphocyte responses. The SEB-reactive Vbeta+ cell
      subpopulations demonstrated a striking tri-phase response in rhesus monkeys
      following an SEB challenge in vivo. The hyperacute down-regulation, seen as early
      as 2 h through 2 days after SEB injection, was characterized by a disappearance
      of the reactive Vbeta-restricted PBL subpopulations from the circulation and
      decreased expression of these cell subpopulations in lymphoid tissues. Following
      this, a dominant expansion of reactive Vbeta-expressing CD4+ cell subpopulations
      occurred in lymph nodes and spleens, whereas in the peripheral blood a
      preferential expansion of reactive Vbeta-expressing CD8+ cell subpopulations was
      seen. An exhaustion of this response was then seen, with a prolonged decrease in
      the number of the reactive Vbeta+ CD4+ lymphocyte subpopulations. Interestingly,
      monoclonal or oligoclonal dominance was seen in the reactive Vbeta+ cell
      subpopulations in the period of the transition from the polyclonal cellular
      expansion to the exhaustion of the response, suggesting that some Vbeta+ cell
      clones may be more resistant than others to superantigen-mediated depletion.
      These results indicate that in vivo SEB superantigen-mediated effect on
      lymphocyte subpopulations in macaques is complex, suggesting that profound
      dynamics in the TCR repertoires may in part account for the susceptibility of
      higher primates to SEB-induced diseases.

PMID- 9590271
TI  - Cytokine gene therapy in experimental allergic encephalomyelitis by injection of
      plasmid DNA-cationic liposome complex into the central nervous system.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the
      central nervous system with many similarities to multiple sclerosis. The main
      effector cells involved are CD4+ T cells, recognizing encephalitogenic epitopes
      within the central nervous system, and macrophages, both of which secrete
      proinflammatory cytokines, such as IFN-gamma and TNF. Studies have shown that
      immunomodulation of this inflammatory response by anti-inflammatory cytokines (IL
      4, IL-10, IFN-beta, and TGF-beta) can reduce clinical severity in EAE. The
      importance of TNF in EAE has been demonstrated by using soluble TNF-receptor
      molecules to inhibit EAE. However, the limitation of this type of therapy is the
      necessity for frequent administration of cytokine proteins due to their short
      biologic half-life. This study demonstrates that EAE can be inhibited by a single
      injection of therapeutic cytokine (IL-4, IFN-beta, and TGF-beta) DNA-cationic
      liposome complex directly into the central nervous system. DNA coding for a
      novel, dimeric form of human p75 TNF receptor also ameliorated clinical EAE.
      Local administration of DNA-cationic liposome complex has identified gene targets
      that may be more efficiently exploited using vectors producing more stable
      expression for effective treatment of neuroimmunologic disease.

PMID- 9590272
TI  - Short peptide-based tolerogens without self-antigenic or pathogenic activity
      reverse autoimmune disease.
AB  - An immunodominant epitope of myelin basic protein (MBP), VHFFKNIVTPRTP (p87-99),
      is a major target of T cells in brain lesions of multiple sclerosis (MS), and
      this peptide can trigger experimental autoimmune encephalomyelitis (EAE). We
      designed truncated peptides based on this pathogenic 13-mer that are not
      antigenic. These short peptides reduced production of IFN-gamma and TNF-alpha in
      vivo. Moreover, paraplegic rats given the 7-mer FKNIVTP in soluble form showed
      total reversal of paralysis in 24 h. Truncated peptides that are too small to
      stimulate antigenic responses to pathogenic regions of myelin basic protein are
      nevertheless effective tolerogens and are able to anergize autoreactive T cells.
      Short peptide-based tolerogens, devoid of immunogenic and pathogenic potential,
      may be attractive for therapy of autoimmune diseases.

PMID- 9590273
TI  - HUGO--a midlife crisis? Human Genome Organisation.

PMID- 9590274
TI  - The lupus paradox.

PMID- 9590275
TI  - The genomics of a hot-water maker.

PMID- 9590276
TI  - Dyskeratosis and ribosomal rebellion.

PMID- 9590277
TI  - Hair hear!

PMID- 9590278
TI  - Sibling rivalry, arrested development and chromosomal mayhem.

PMID- 9590279
TI  - The politics of germline therapy.

PMID- 9590280
TI  - The kinetics of rAAV integration in the liver.

PMID- 9590281
TI  - An imprinted antisense RNA overlaps UBE3A and a second maternally expressed
      transcript.

PMID- 9590282
TI  - HNPCC associated with germline mutation in the TGF-beta type II receptor gene.

PMID- 9590283
TI  - The impact of L1 retrotransposons on the human genome.
AB  - The 'master' human mobile element, the L1 retrotransposon, has come of age as a
      biological entity. Knowledge of how it retrotransposes in vivo, how its proteins
      act to retrotranspose other poly A elements and the extent of its role in shaping
      the human genome should emerge rapidly over the next few years. We review the
      impact of retrotransposons and how new insight is likely to lead to important
      practical applications for these intriguing mobile elements.

PMID- 9590284
TI  - A mouse model for Prader-Willi syndrome imprinting-centre mutations.
AB  - Imprinting in the 15q11-q13 region involves an 'imprinting centre' (IC), mapping
      in part to the promoter and first exon of SNRPN. Deletion of this IC abolishes
      local paternally derived gene expression and results in Prader-Willi syndrome
      (PWS). We have created two deletion mutations in mice to understand PWS and the
      mechanism of this IC. Mice harbouring an intragenic deletion in Snrpn are
      phenotypically normal, suggesting that mutations of SNRPN are not sufficient to
      induce PWS. Mice with a larger deletion involving both Snrpn and the putative PWS
      IC lack expression of the imprinted genes Zfp127 (mouse homologue of ZNF127), Ndn
      and Ipw, and manifest several phenotypes common to PWS infants. These data
      demonstrate that both the position of the IC and its role in the coordinate
      expression of genes is conserved between mouse and human, and indicate that the
      mouse is a suitable model system in which to investigate the molecular mechanisms
      of imprinting in this region of the genome.

PMID- 9590285
TI  - X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene
      with putative nucleolar functions.
AB  - X-linked recessive dyskeratosis congenita (DKC) is a rare bone-marrow failure
      disorder linked to Xq28. Hybridization screening with 28 candidate cDNAs resulted
      in the detection of a 3' deletion in one DKC patient with a cDNA probe (derived
      from XAP101). Five different missense mutations in five unrelated patients were
      subsequently identified in XAP101, indicating that it is the gene responsible for
      X-linked DKC (DKC1). DKC1 is highly conserved across species barriers and is the
      orthologue of rat NAP57 and Saccharomyces cerevisiae CBF5. The peptide dyskerin
      contains two TruB pseudouridine (psi) synthase motifs, multiple phosphorylation
      sites, and a carboxy-terminal lysine-rich repeat domain. By analogy to the
      function of the known dyskerin orthologues, involvement in the cell cycle and
      nucleolar function is predicted for the protein.

PMID- 9590286
TI  - Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation
      induced G1 arrest.
AB  - Chromosome 3q alterations occur frequently in many types of tumours. In a genetic
      screen for loci present in rhabdomyosarcomas, we identified an isochromosome 3q
      [i(3q)], which inhibits muscle differentiation when transferred into myoblasts.
      The i(3q) inhibits MyoD function, resulting in a non-differentiating phenotype.
      Furthermore, the i(3q) induces a 'cut' phenotype, abnormal centrosome
      amplification, aneuploidy and loss of G1 arrest following gamma-irradiation.
      Testing candidate genes within this region reveals that forced expression of
      ataxia-telangiectasia and rad3-related (ATR) results in a phenocopy of the i(3q).
      Thus, genetic alteration of ATR leads to loss of differentiation as well as cell
      cycle abnormalities.

PMID- 9590287
TI  - Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail
      patella syndrome.
AB  - The LIM-homeodomain protein Lmx1b plays a central role in dorso-ventral
      patterning of the vertebrate limb. Targeted disruption of Lmx1b results in
      skeletal defects including hypoplastic nails, absent patellae and a unique form
      of renal dysplasia (see accompanying manuscript by H. Chen et al.; ref. 2). These
      features are reminiscent of the dominantly inherited skeletal malformation nail
      patella syndrome (NPS). We show that LMX1B maps to the NPS locus and that three
      independent NPS patients carry de novo heterozygous mutations in this gene.
      Functional studies show that one of these mutations disrupts sequence-specific
      DNA binding, while the other two mutations result in premature termination of
      translation. These data demonstrate a unique role for LMX1B in renal development
      and in patterning of the skeletal system, and suggest that alteration of
      Lmx1b/LMX1B function in mice and humans results in similar phenotypes.
      Furthermore, we provide evidence for the first described mutations in a LIM
      homeodomain protein which account for an inherited form of abnormal skeletal
      patterning and renal failure.

PMID- 9590288
TI  - Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in
      human nail patella syndrome.
AB  - Dorsal-ventral limb patterning in vertebrates is thought to be controlled by the
      LIM-homeodomain protein Lmx1b which is expressed in a spatially and temporally
      restricted manner along the dorsal-ventral limb axis. Here we describe the
      phenotype resulting from targeted disruption of Lmx1b. Our results demonstrate
      that Lmx1b is essential for the specification of dorsal limb fates at both the
      zeugopodal and autopodal level with prominent phenotypes including an absence of
      nails and patellae. These features are similar to those present in a dominantly
      inherited human condition called nail patella syndrome (NPS), which also has
      renal involvement. Mouse Lmx1b maps to a region syntenic to that of the NPS gene,
      and kidneys of Lmx1b mutant mice exhibit pathological changes similar to that
      observed in NPS (refs 5,6). Our results demonstrate an essential function for
      Lmx1b in mouse limb and kidney development and suggest that NPS might result from
      mutations in the human LMX1B gene.

PMID- 9590289
TI  - Homozygous C1q deficiency causes glomerulonephritis associated with multiple
      apoptotic bodies.
AB  - The complement system plays a paradoxical role in the development and expression
      of autoimmunity in humans. The activation of complement in systemic lupus
      erythematosus (SLE) contributes to tissue injury. In contrast, inherited
      deficiency of classical pathway components, particularly C1q (ref. 1), is
      powerfully associated with the development of SLE. This leads to the hypothesis
      that a physiological action of the early part of the classical pathway protects
      against the development of SLE (ref. 2) and implies that C1q may play a key role
      in this respect. C1q-deficient (C1qa-/-) mice were generated by gene targeting
      and monitored for eight months. C1qa-/- mice had increased mortality and higher
      titres of autoantibodies, compared with strain-matched controls. Of the C1qa-/-
      mice, 25% had glomerulonephritis with immune deposits and multiple apoptotic cell
      bodies. Among mice without glomerulonephritis, there were significantly greater
      numbers of glomerular apoptotic bodies in C1q-deficient mice compared with
      controls. The phenotype associated with C1q deficiency was modified by background
      genes. These findings are compatible with the hypothesis that C1q deficiency
      causes autoimmunity by impairment of the clearance of apoptotic cells.

PMID- 9590291
TI  - SMN oligomerization defect correlates with spinal muscular atrophy severity.
AB  - Spinal muscular atrophy (SMA) is a motor-neuron disorder resulting from anterior
      horn-cell death. The autosomal recessive form has a carrier frequency of 1 in 50
      and is the most common genetic cause of infant death. SMA is categorized as types
      I-III, ranging from severe to mild, based upon age of onset and clinical course.
      Two closely flanking copies of the survival motor neuron (SMN) gene are on
      chromosome 5q13 (ref. 1). The telomeric SMN (SMN1) copy is homozygously deleted
      or converted in >95% of SMA patients, while a small number of SMA disease alleles
      contain missense mutations within the carboxy terminus. We have identified a
      modular oligomerization domain within exon 6 of SMN1. All previously identified
      missense mutations map within or immediately adjacent to this domain. Comparison
      of wild-type to mutant SMN proteins of type I, II and III SMA patients showed a
      direct correlation between oligomerization and clinical type. Moreover, the most
      abundant centromeric SMN product, which encodes exons 1-6 but not 7, demonstrated
      reduced self-association. These findings identify decreased SMN self-association
      as a biochemical defect in SMA, and imply that disease severity is proportional
      to the intracellular concentration of oligomerization-competent SMN proteins.

PMID- 9590290
TI  - Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic
      hearing impairment.
AB  - The tectorial membrane is an extracellular matrix of the inner ear that contacts
      the stereocilia bundles of specialized sensory hair cells. Sound induces movement
      of these hair cells relative to the tectorial membrane, deflects the stereocilia,
      and leads to fluctuations in hair-cell membrane potential, transducing sound into
      electrical signals. Alpha-tectorin is one of the major non-collagenous components
      of the tectorial membrane. Recently, the gene encoding mouse alpha-tectorin
      (Tecta) was mapped to a region of mouse chromosome 9, which shows evolutionary
      conservation with human chromosome 11q (ref. 3), where linkage was found in two
      families, one Belgian (DFNA12; ref. 4) and the other, Austrian (DFNA8;
      unpublished data), with autosomal dominant non-syndromic hearing impairment. We
      determined the complete sequence and the intron-exon structure of the human TECTA
      gene. In both families, mutation analysis revealed missense mutations which
      replace conserved amino-acid residues within the zona pellucida domain of TECTA.
      These findings indicate that mutations in TECTA are responsible for hearing
      impairment in these families, and implicate a new type of protein in the
      pathogenesis of hearing impairment.

PMID- 9590292
TI  - SHOX mutations in dyschondrosteosis (Leri-Weill syndrome).
AB  - Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia with
      deformity of the forearm (Madelung deformity; ref. 3). Based on the observation
      of XY translocations (p22,q12; refs 4-6) in DCS patients, we tested the
      pseudoautosomal region in eight families with DCS and showed linkage of the DCS
      gene to a microsatellite DNA marker at the DXYS233 locus (Zmax=6.26 at theta=0).
      The short stature homeobox-containing gene (SHOX), involved in idiopathic growth
      retardation and possibly Turner short stature, maps to this region and was
      therefore regarded as a strong candidate gene in DCS. Here, we report large-scale
      deletions (in seven families) and a nonsense mutation (in one family) of SHOX in
      patients with DCS and show that Langer mesomelic dwarfism results from homozygous
      mutations at the DCS locus.

PMID- 9590293
TI  - Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill
      dyschondrosteosis.
AB  - Leri-Weill Dyschondrosteosis (LWD; OMIM 127300) is a dominantly inherited
      skeletal dysplasia characterized by disproportionate short stature with
      predominantly mesomelic limb shortening. Expression is variable and consistently
      more severe in females, who frequently display the Madelung deformity of the
      forearm (shortening and bowing of the radius with dorsal subluxation of the
      distal ulna). The rare Langer Mesomelic Dysplasia (LD; OMIM 249700),
      characterized by severe short stature with hypoplasia/aplasia of the ulna and
      fibula, has been postulated to be the homozygous form of LWD (refs 4-6). In a six
      generation pedigree with LWD, we established linkage to the marker DXYS6814 in
      the pseudoautosomal region (PAR1) of the X and Y chromosomes (Z max=6.28;
      theta=0). Linkage analysis of three smaller pedigrees increased the lod score to
      8.68 (theta=0). We identified submicroscopic PAR1 deletions encompassing the
      recently described short stature homeobox-containing gene SHOX (refs 7,8)
      segregating with the LWD phenotype in 5 families. A point mutation leading to a
      premature stop in exon 4 of SHOX was identified in one LWD family.

PMID- 9590294
TI  - Human deltex is a conserved regulator of Notch signalling.
AB  - A fundamental cell-fate control mechanism regulating multicellular development is
      defined by the Notch-signalling pathway. Developmental and genetic studies of
      wild type and activated Notch-receptor expression in diverse organisms suggest
      that Notch plays a general role in development by governing the ability of
      undifferentiated precursor cells to respond to specific signals. Notch signalling
      has been conserved throughout evolution and controls the differentiation of a
      broad spectrum of cell types during development. Genetic studies in Drosophila
      have led to the identification of several components of the Notch pathway. Two of
      the positive regulators of the pathway are encoded by the suppressor of hairless
      [Su(H)] and deltex (dx) genes. Drosophila dx encodes a ubiquitous, novel
      cytoplasmic protein of unknown biochemical function. We have cloned a human
      deltex homologue and characterized it in parallel with its Drosophila counterpart
      in biochemical assays to assess deltex function. Both human and Drosophila deltex
      bind to Notch across species and carry putative SH3-binding domains. Using the
      yeast interaction trap system, we find that Drosophila and human deltex bind to
      the human SH3-domain containing protein Grb2 (ref. 10). Results from two
      different reporter assays allow us for the first time to associate deltex with
      Notch-dependent transcriptional events. We present evidence linking deltex to the
      modulation of basic helix-loop-helix (bHLH) transcription factor activity.

PMID- 9590295
TI  - Skeletal muscle-specific expression of a utrophin transgene rescues utrophin
      dystrophin deficient mice.
AB  - Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease usually
      resulting in death of patients by their early twenties. In contrast, mice lacking
      dystrophin (Dmd(mdx)), appear physically normal despite their underlying muscle
      pathology. Mice deficient for both dystrophin and the dystrophin-related protein,
      utrophin, (Dmd(mdx);Utrn-/- mice) die between 6 and 20 weeks of age suffering
      from severe muscle weakness with joint contractures, pronounced growth
      retardation and kyphosis, suggesting that dystrophin and utrophin play
      complementary roles. The exact cause of death in these mice was not determined.
      Here we show that expression of a truncated utrophin transgene solely within the
      skeletal muscle of these mutants prevents premature death and the development of
      any clinical phenotype. In the absence of full-length dystrophin and utrophin,
      the presence of truncated utrophin also decreases muscle fibre regeneration,
      relocalizes the dystrophin protein complex to the sarcolemma and re-establishes a
      normal expression pattern of developmental muscle proteins. These data suggest
      that Dmd(mdx);Utrn-/- mice succumb to a skeletal muscle defect and that their
      reduced lifespan is not due to cardiac or neurogenic components. The phenotypic
      rescue observed demonstrates that the Dmd(mdx);Utrn-/- mice are an ideal model
      for testing gene delivery protocols for the expression of utrophin or dystrophin
      in skeletal muscle. To determine the cause of death of the Dmd(mdx):Utrn-/- mice.

PMID- 9590296
TI  - PAX8 mutations associated with congenital hypothyroidism caused by thyroid
      dysgenesis.
AB  - Permanent congenital hypothyroidism (CH) is a common disease that occurs in 1 of
      3,000-4,000 newborns. Except in rare cases due to hypothalamic or pituitary
      defects, CH is characterized by elevated levels of thyroid-stimulating hormone
      (TSH) resulting from reduced thyroid function. When thyroid hormone therapy is
      not initiated within the first two months of life, CH can cause severe
      neurological, mental and motor damage. In 80-85% of cases, CH is associated with
      and presumably is a consequence of thyroid dysgenesis (TD). In these cases, the
      thyroid gland can be absent (agenesis, 35-40%), ectopically located (30-45%)
      and/or severely reduced in size (hypoplasia, 5%). Familial cases of TD are rare,
      even though ectopic or absent thyroid has been occasionally observed in siblings.
      The pathogenesis of TD is still largely unknown. Although a genetic component has
      been suggested, mutations in the gene encoding the receptor for the thyroid
      stimulating hormone (TSHR) have been identified in only two cases of TD with
      hypoplasia. We report mutations in the coding region of PAX8 in two sporadic
      patients and one familial case of TD. All three point mutations are located in
      the paired domain of PAX8 and result in severe reduction of the DNA-binding
      activity of this transcription factor. These genetic alterations implicate PAX8
      in the pathogenesis of TD and in normal thyroid development.

PMID- 9590297
TI  - Follicular cells of the thyroid gland require Pax8 gene function.
AB  - The thyroid gland develops from two distinct embryonic lineages: follicular cells
      (which produce thyroxine) and parafollicular C-cells (which produce calcitonin)
      are of endodermal and neural crest origin, respectively. Little is known about
      the molecular mechanisms governing the generation of these different cell types.
      Mice lacking the transcription factor Ttf1 lack both cell types and thus are
      unable to develop a thyroid gland. By analysis of Pax8-/- mice, we demonstrate
      that Pax8 is required for the formation of the follicular cells in the thyroid.
      We present evidence that Pax8 is necessary for providing cues for the
      differentiation of competent endoderm primordia into thyroxin-producing
      follicular cells.

PMID- 9590298
TI  - Correction of disease-causing CBS mutations in yeast.
AB  - Mutations in cystathionine beta-synthase (CBS) are known to cause homocystinuria,
      a recessive disorder characterized by excessive levels of total homocysteine
      (tHcy) in plasma. The primary cause of mortality is thromboembolism induced by
      the excessive tHcy levels. Mild increases in tHcy levels are a significant risk
      factor in the development of vascular disease in the general population. This can
      result from heterozygosity at the CBS locus or polymorphic variation in other
      enzymes involved in homocysteine re-methylation. We report here that a mutation
      which deletes the carboxy-terminal 145 amino acids of CBS can functionally
      suppress the phenotype of several CBS mutant alleles found in homocystinurics
      when expressed in yeast. This C-terminal domain of CBS acts to inhibit enzymatic
      activity and is in turn regulated by S-adenosylmethionine (AdoMet), a positive
      effector of CBS. Our results indicate that most mutations found in
      homocystinurics do not cause dysfunction of the catalytic domain, but rather
      interfere with the activation of the enzyme. These findings suggest a new drug
      target to treat homocystinuria and homocysteine-related vascular disease.

PMID- 9590299
TI  - Mutations in the integrin alpha7 gene cause congenital myopathy.
AB  - The basal lamina of muscle fibers plays a crucial role in the development and
      function of skeletal muscle. An important laminin receptor in muscle is integrin
      alpha7beta1D. Integrin beta1 is expressed throughout the body, while integrin
      alpha7 is more muscle-specific. To address the role of integrin alpha7 in human
      muscle disease, we determined alpha7 protein expression in muscle biopsies from
      117 patients with unclassified congenital myopathy and congenital muscular
      dystrophy by immunocytochemistry. We found three unrelated patients with integrin
      alpha7 deficiency and normal laminin alpha2 chain expression. To determine if any
      of these three patients had mutations of the integrin alpha7 gene, ITGA7, we
      cloned and sequenced the full-length human ITGA7 cDNA, and screened the patients
      for mutations. One patient had splice mutations on both alleles; one causing a 21
      bp insertion in the conserved cysteine-rich region, and the other causing a 98-bp
      deletion. A second patient was a compound heterozygote for the same 98-bp
      deletion, and had a 1-bp frame-shift deletion on the other allele. A third showed
      marked deficiency of ITGA7 mRNA. Clinically, these patients showed congenital
      myopathy with delayed motor milestones. Our results demonstrate that mutations in
      ITGA7 are involved in a form of congenital myopathy.

PMID- 9590300
TI  - Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon
      Longitudinal Study of Pregnancy and Childhood.
AB  - Size at birth is an important determinant of perinatal survival and has also been
      associated with the risk for cardiovascular disease and type 2 diabetes in adult
      life. Common genetic variation that regulates fetal growth could therefore
      influence perinatal survival and predispose to the development of adult disease.
      We have tested the insulin gene (INS) variable number of tandem repeats (VNTR)
      locus, which in Caucasians has two main allele sizes (class I and class III; ref.
      3), as a functional candidate polymorphism for association with size at birth, as
      it has been shown to influence transcription of INS (refs 3-5). In a cohort of
      758 term singletons (Avon Longitudinal Study of Pregnancy and Childhood; ALSPAC)
      followed longitudinally from birth to 2 years, we detected significant genetic
      associations with size at birth: class III homozygotes had larger mean head
      circumference (P=0.004) than class I homozygotes. These associations were
      amplified in babies who did not show postnatal realignment of growth (45%), and
      were also evident for length (P=0.015) and weight (P=0.009) at birth. The INS
      VNTR III/II genotype might have bestowed a perinatal survival during human
      history by conferring larger size at birth. Common genetic variation of this kind
      may contribute to reported associations between birth size and adult disease.

PMID- 9590301
TI  - Gastric tonometry: the canary sings once again.

PMID- 9590302
TI  - Synergistic sedation: some credible data and a word of caution.

PMID- 9590303
TI  - A night in Tunisia.

PMID- 9590304
TI  - Parenteral nutrition in trauma patients: glucose-based, lipid-based, or none?

PMID- 9590305
TI  - A yellow light for nitric oxide synthase inhibitors in sepsis: proceed with
      caution.

PMID- 9590306
TI  - Acute pancreatitis: further insight into mechanisms.

PMID- 9590307
TI  - Interleukin-10: the ambiguity in sepsis continues.

PMID- 9590308
TI  - Vasoactive prostanoids and traumatic brain injury.

PMID- 9590309
TI  - Utility and feasibility of assessing myocardial mechanics after bypass.

PMID- 9590310
TI  - Phasic expiratory tracheal gas insufflation: short but sweet.

PMID- 9590311
TI  - Gastric intramucosal acidosis in mechanically ventilated patients: role of
      mucosal blood flow.
AB  - OBJECTIVE: To investigate whether gastric intramucosal acidosis is associated
      with a decreased gastric mucosal blood flow in mechanically ventilated patients.
      DESIGN: Prospective, clinical investigation. SETTING: University hospital
      intensive care unit. PATIENTS: Seventeen mechanically ventilated patients with
      stable hemodynamic status. INTERVENTIONS: Gastric tonometry and endoscopic
      assessment of mucosal blood flow. MEASUREMENTS AND MAIN RESULTS: Six patients had
      gastric intramucosal acidosis (intramucosal pH [pHi] of 7.24 +/- 0.06), whereas
      the remaining 11 patients had pHi values within the normal range (7.44 +/- 0.01).
      No differences were found between intramucosal acidotic and nonacidotic patients
      with respect to their general and hemodynamic characteristics. Patients with
      intramucosal acidosis had a lower gastric mucosal blood flow, as assessed by
      laser-Doppler flowmetry, than nonacidotic patients (1.4 +/- 0.1 vs. 2.1 +/- 0.2
      volts, respectively; p < .05). Reflectance spectrophotometry disclosed that
      patients with low gastric pHi had also a significantly (p < .05) lower hemoglobin
      content index (61 +/- 4 arbitrary units) than patients with normal pHi (81 +/- 3
      arbitrary units), whereas oxygen saturation index was similar for both groups.
      CONCLUSION: Our results support the hypothesis that gastric mucosal hypoperfusion
      underlies the development of intramucosal acidosis in mechanically ventilated
      patients.

PMID- 9590312
TI  - Effects of partial liquid ventilation on lung injury in a model of acute
      respiratory failure: a histologic and morphometric analysis.
AB  - OBJECTIVE: To compare the histopathologic changes observed in a sheep model of
      oleic acid-induced acute respiratory failure during partial liquid ventilation
      with perflubron with gas ventilation. DESIGN: Randomized, controlled study.
      SETTING: Animal laboratory and pathology laboratories of a university hospital.
      SUBJECTS: Fourteen healthy adult sheep, weighing 64.9 +/- 6.4 kg. INTERVENTIONS:
      Lung injury was induced with oleic acid (0.15 mL/kg). A tracheostomy tube was
      inserted, along with systemic and pulmonary artery monitoring catheters. Animals
      were randomized to undergo either partial liquid ventilation (n = 7) or gas
      ventilation (n = 7). Animals underwent euthanasia at the end of the 90-min study
      period, after which the endotracheal tube was clamped with the lungs in
      expiratory hold at a positive end-expiratory pressure of 5 cm H2O. En bloc
      excision of the heart and lungs was performed by thoracotomy. Perfusion of the
      isolated lung vasculature with 2.5% paraformaldehyde and 0.25% glutaraldehyde in
      a 0.1-M phosphate buffer was performed. Histologic analysis followed.
      MEASUREMENTS AND MAIN RESULTS: Gas exchange increased markedly in the animals
      that underwent partial liquid ventilation compared with the gas-ventilated
      animals (PaO2 at 90 mins: gas ventilation-treatment group, 40 +/- 8 torr [5.3 +/-
      1.1 kPa]; partial liquid ventilation-treatment group, 108 +/- 60 torr [14.4 +/-
      8.0 kPa]; p = .004). Lung histologic analysis demonstrated a better overall
      diffuse alveolar damage score (partial liquid ventilation-treatment group, 12.4
      +/- 1.4; gas ventilation-treatment group, 15.0 +/- 1.7; p = .01). In the partial
      liquid ventilation-treatment group, we observed an increase in mean alveolar
      diameter (partial liquid ventilation-treatment group, 82.4 +/- 2.9 microm; gas
      ventilation-treatment group, 67.7 x 3.9 microm; p = .0022) and a decrease in the
      number of alveoli per high-power field (partial liquid ventilation-treatment
      group, 25.7 +/- 0.9, gas ventilation-treatment group, 31.4 +/- 2.5; p = .0022),
      in septal wall thickness (partial liquid ventilation-treatment group, 6.0 +/- 0.6
      microm; gas ventilation-treatment group, 8.3 +/- 1.0 microm; p = .0033), and in
      mean capillary diameter (partial liquid ventilation-treatment group, 13.0 +/- 0.8
      microm; gas ventilation-treatment group, 19.9 +/- 1.4 microm; p = .0022).
      CONCLUSIONS: Partial liquid ventilation is associated with notable improvement in
      gas exchange and with a reduction in the histologic and morphologic changes
      observed in an oleic acid model of acute lung injury.

PMID- 9590313
TI  - Synergistic sedation with propofol and midazolam in intensive care patients after
      coronary artery bypass grafting.
AB  - OBJECTIVES: To evaluate and compare the clinical efficacy, impact on
      hemodynamics, safety profiles, and cost of combined administration of propofol
      and midazolam (synergistic sedation) vs. midazolam and propofol administered as
      sole agents, for sedation of mechanically ventilated patients after coronary
      artery bypass grafting. DESIGN: Prospective, controlled, randomized, double-blind
      clinical trial. SETTING: Intensive care unit of SCIAS-Hospital de Barcelona.
      PATIENTS: Seventy-five mechanically ventilated patients who underwent coronary
      artery bypass graft surgery under low-dose opioid anesthesia. INTERVENTIONS:
      According to the double-blind method, patients were randomly assigned to receive
      propofol (n = 25), midazolam (n = 25), or propofol combined with midazolam (n =
      25). Infusion rates were adjusted to stay between 8 and 11 points on Glasgow Coma
      Score modified by Cook and Palma. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD
      duration of sedation was 14.4 +/- 1.5 hrs, 14.1 +/- 1.1 hrs, and 14.7 +/- 1.9 hrs
      for the propofol, midazolam, and synergistic groups, respectively. The induction
      dose was 0.55 +/- 0.05 mg/kg for propofol as sole agent, 0.05 +/- 0.01 mg/kg for
      midazolam as sole agent, and 0.22 +/- 0.03 mg/kg for propofol administered in
      combination with 0.02 +/- 0.00 mg/kg of midazolam (p = .001). The maintenance
      dose was 1.20 +/- 0.03 mg/kg/hr for propofol as sole agent, 0.08 +/- 0.01
      mg/kg/hr for midazolam as sole agent, and 0.50 +/- 0.09 mg/kg/hr for propofol
      administered in combination with 0.03 +/- 0.01 mg/kg/hr of midazolam (p < .001).
      All sedative regimens achieved similar efficacy in percentage of hours of
      adequate sedation (93% for propofol, 88% for midazolam, and 90% for the
      synergistic group, respectively). After induction, both propofol and midazolam
      groups had significant decreases in systolic blood pressure, diastolic blood
      pressure, left atrial pressure, and heart rate. Patients in the synergistic group
      had significant bradycardia throughout the study, without impairment in other
      hemodynamic parameters. Patients sedated with propofol or synergistic regimen
      awoke sooner and could be extubated before those patients sedated with midazolam
      (0.9 +/- 0.3 hrs and 1.2 +/- 0.6 hrs vs. 2.3 +/- 0.8 hrs, respectively, p = .01).
      Synergistic sedation produced cost savings of 28% with respect to midazolam and
      68% with respect to propofol. CONCLUSIONS: In the study conditions, the new
      synergistic treatment with propofol and midazolam administered together is an
      effective and safe alternative for sedation, with some advantages over the
      conventional regimen with propofol or midazolam administered as sole agents, such
      as absence of hemodynamic impairment, >68% reduction in maintenance dose, and
      lower pharmaceutical cost.

PMID- 9590314
TI  - Predictive value of severity scoring systems: comparison of four models in
      Tunisian adult intensive care units.
AB  - OBJECTIVES: To compare the performance of four severity scoring systems: the
      Acute Physiology and Chronic Health Evaluation (APACHE) II, the new versions of
      the Mortality Prediction Model (MPM0 and MPM24), and the Simplified Acute
      Physiology Score (SAPS) II. DESIGN: A prospective cohort study. SETTING: Three
      Tunisian intensive care units (ICUs). PATIENTS: Consecutive, unselected adult
      patients (n = 1325). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall,
      observed death rates were higher than predicted by all models except MPM0. All
      the evaluated scoring systems had good discrimination power as expressed by area
      under the receiver operating characteristics curve, but their calibration was
      less perfect when compared with original validation reports. There were no major
      differences between the models with regard either to discrimination or
      calibration performance. CONCLUSION: Despite an overall good discrimination,
      APACHE II, MPM0, MPM24, and SAPS II showed a less satisfactory calibration in our
      Tunisian sample of ICU patients. Part of the models inaccuracy could be related
      to quality of care problems in our ICUs, but this issue needs further analysis.

PMID- 9590315
TI  - Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on
      glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in
      critically ill patients.
AB  - OBJECTIVE: To compare the effects of isocaloric, isonitrogenous carbohydrate
      nutrition vs. lipid-based total parenteral nutrition on respiratory gas exchange
      and intermediary metabolism in critically ill patients. DESIGN: Prospective,
      clinical trial. SETTING: Surgical intensive care unit in a major university
      hospital in Switzerland. PATIENTS: Sixteen patients admitted to the surgical
      intensive care unit. INTERVENTIONS: Patients were randomized to receive
      isocaloric isonitrogenous total parenteral nutrition (TPN) containing 75% (TPN
      glucose) or 15% (TPN-lipid) glucose over a 5-day period. MEASUREMENTS AND MAIN
      RESULTS: Indirect glucose metabolism was assessed from plasma carbon-13 (13C)
      labeled glucose and 13C-labeled CO2 production during a tracer infusion of
      uniformly 13C-labeled glucose, and de novo lipogenesis was estimated from the
      incorporation of 13C into palmitate-very low density lipoproteins (VLDL) during a
      tracer infusion of 1-(13)C acetate. Compared with TPN-lipid, TPN-glucose
      increased plasma glucose more (by 26% vs. 7%, p < .05), increased insulin more
      (by 284% vs. 40%, p < .01), and increased total CO2 more (by 15% vs. 0%, p <
      .01). Both nutrient mixtures failed to inhibit endogenous glucose production and
      net protein oxidation, suggesting absence of suppression of gluconeogenesis.
      Fractional de novo lipogenesis was markedly increased by TPN-glucose to 17.4% vs.
      3.3% with TPN lipids. CONCLUSIONS: The rate of glucose administration commonly
      used during TPN of critically ill patients does not suppress endogenous glucose
      production or net protein loss, but markedly stimulates de novo lipogenesis and
      CO2 production. Increasing the proportion of fat may be beneficial, provided that
      lipid emulsion has no adverse effects.

PMID- 9590316
TI  - Apnea testing guided by continuous transcutaneous monitoring of partial pressure
      of carbon dioxide.
AB  - OBJECTIVE: To continuously monitor PCO2 during two different protocols for apnea
      testing as part of the determination of brain death. DESIGN: Prospective
      comparative study using continuous transcutaneous PCO2 (tcPCO2) monitoring in 54
      apnea tests with or without artificial CO2 augmentation. Another 53 apnea tests
      were not continuously monitored. SETTING: Intensive care wards in Northern
      Bavaria. PATIENTS: Ninety-six consecutive patients with suspected brain death.
      INTERVENTIONS: Apnea tests guided by transcutaneous monitoring during a PaCO2 of
      > or = 60 torr (> or = 8 kPa). MEASUREMENTS AND MAIN RESULTS: The mean of the
      difference between tcPCO2 and PaCO2 was -0.26 +/- 1.16 (SEM) torr (-0.035 +/-
      0.15 kPa). Seventy percent of all transcutaneous measurements were within +/-10%
      of the PaCO2 values. The individual differences ranged from -25.8 to 16.9 torr (
      3.44 to 2.25 kPa). CONCLUSIONS: While not as precise as could be desired in
      individual cases, the overall agreement between tcPCO2 and PaCO2 was good.
      Transcutaneous monitoring aided in effectively reducing the CO2 target overshoot
      with artificial CO2 augmentation, reduced the necessary number of blood gas
      checks compared with a former study, using predetermined time-locked evaluations,
      and prolonged only tests with artificial CO2 augmentation.

PMID- 9590317
TI  - Removal of endotoxin and cytokines by plasma exchange in patients with acute
      hepatic failure.
AB  - OBJECTIVES: To compare the circulating concentrations of endotoxin and cytokines
      in patients with fulminant hepatitis and patients with the severe form of acute
      hepatitis, and to assess the effects of plasma exchange on the circulating
      concentrations of these inflammatory mediators in patients with acute hepatic
      failure. DESIGN: Prospective, consecutive entry study of patients meeting
      fulminant hepatitis criteria and the severe form of acute hepatitis criteria.
      SETTING: University hospital, intensive care unit. PATIENTS: Five patients with
      fulminant hepatitis, eight patients with the severe form of acute hepatitis, two
      patients with acute-on-chronic hepatic failure, and one patient with
      postoperative hepatic failure. INTERVENTIONS: Plasma endotoxin, serum tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined on
      admission in five patients with fulminant hepatitis and eight patients with the
      severe form of acute hepatitis. Circulating concentrations of the inflammatory
      mediators were measured before and after a single course of plasma exchange in
      eight patients with acute liver failure, including five patients with fulminant
      hepatitis, two patients with acute-on-chronic hepatic failure, and one patient
      with postoperative hepatic failure. MEASUREMENTS AND MAIN RESULTS: TNF-alpha and
      IL-6 in patients with fulminant hepatitis were significantly higher than in
      patients with the severe form of acute hepatitis, whereas endotoxin
      concentrations did not differ between patients with fulminant hepatitis or the
      severe form of acute hepatitis. IL-1beta was not detectable in patients with
      either fulminant hepatitis or the severe form of acute hepatitis. Plasma
      endotoxin concentrations decreased immediately after plasma exchange. Serum
      concentrations of TNF-alpha and IL-6 were significantly lower after plasma
      exchange than before plasma exchange. CONCLUSION: TNF-alpha and IL-6 may be
      important in the pathogenesis of the clinical symptoms that differentiate
      fulminant hepatitis from the severe form of acute hepatitis, and plasma exchange
      removes these inflammatory mediators from the circulation of patients with severe
      liver disease.

PMID- 9590318
TI  - Response of the septic vasculature to prolonged vasopressor therapy with N(omega)
      monomethyl-L-arginine and epinephrine in canines.
AB  - OBJECTIVE: To investigate the effect of blocking nitric oxide production on
      cardiovascular function and survival in canine septic shock treated with or
      without a conventional vasopressor. DESIGN: Randomized, controlled trial.
      SETTING: An animal research laboratory at the National Institutes of Health.
      SUBJECTS: Sixty purpose-bred beagles. INTERVENTIONS: Fibrin clots containing
      Escherichia coli were surgically placed into the peritoneal cavity. N(omega)
      monomethyl-L-arginine (L-NMMA) 10 mg/kg followed by 0.5, 1.0, or 4.0 mg/kg/hr),
      epinephrine (1 microg/kg/min), both, or neither were infused for 24 hrs beginning
      6 hrs after the onset of infection. All animals received fluid and antibiotic
      therapy. MEASUREMENTS AND MAIN RESULTS: Serum nitric oxide metabolites, nitrite
      and nitrate, increased with infection (p = .024) and decreased with L-NMMA (p =
      .004, all doses combined). Myocardial nitric oxide synthase activity was ranked
      as follows: nonsurvivors > survivors > noninfected controls (p < .01). Other
      tissues examined showed the same pattern. L-NMMA produced sustained increases in
      systemic vascular resistance index and mean arterial pressure 9 and 24 hrs after
      the onset of infection (p < or = .04). Left ventricular ejection fraction was
      depressed by septic shock (p = .01) and further decreased by L-NMMA (p = .02).
      However, control and L-NMMA cardiac index values were similar (p > .4), perhaps
      because L-NMMA increased pulmonary artery occlusion pressure (p = .02). From 9 to
      24 hrs, epinephrine, in the absence or presence of L-NMMA, blunted recovery of
      cardiac index (p < .02) and had a diminishing vasopressor effect (p = .05).
      Neither L-NMMA nor epinephrine, individually or combined, significantly altered
      survival rates at the doses investigated (p > or = .69). CONCLUSIONS: The tested
      doses showed that nitric oxide production was inhibited by L-NMMA in canine
      septic shock, but mortality and myocardial depression were unaffected. These
      results suggest that if L-NMMA has a beneficial effect on survival rates in
      septic shock, it is small.

PMID- 9590319
TI  - Acute-phase response of the rat pancreas protects against further aggression with
      severe necrotizing pancreatitis.
AB  - OBJECTIVE: To test the hypothesis that the specific acute-phase response program
      of the pancreas is a powerful emergency defense mechanism that is beneficial
      during acute pancreatitis. DESIGN: Prospective, randomized, controlled animal
      study. SETTING: Research laboratory in a university medical school. SUBJECTS:
      Female Wistar rats, weighing 250 to 300 g. INTERVENTIONS: An acute-phase response
      was induced in rats subjected to hyperstimulation with cerulein. The development
      of the acute-phase reaction was monitored by the expression of the pancreatitis
      associated protein I. In control animals, no acute-phase response was induced.
      After the first experimental procedure at periods of 2, 48, or 168 hrs, the
      pancreas was challenged by inducing severe necrotizing pancreatitis with
      retrograde infusion of taurocholate into the pancreatic duct. The course of
      necrohemorrhagic pancreatitis and survival of the rats to the challenge was
      monitored with time. MEASUREMENTS AND MAIN RESULTS: Forty-eight hours after the
      onset of edematous pancreatitis, the acute-phase response was strong, as judged
      by the overexpression of mRNA, which encoded the pancreatitis-associated protein
      I, and the resulting increase in concentrations of this protein in the pancreas.
      When necrotizing pancreatitis was induced, the survival rate was significantly
      higher than in the corresponding control group. In contrast, expression of the
      pancreatitis-associated protein I was not detectable after 2 hrs, indicating that
      the acute phase had not fully developed, nor after 168 hrs when the acute phase
      had ended. In both cases, challenge by necrotizing pancreatitis led to similar
      survival rates in cerulein-treated and control rats. CONCLUSIONS: The acute-phase
      response of the pancreas seems to be a powerful emergency defense mechanism
      against further pancreatic aggression, as shown by the improved survival of the
      animals. The factors mediating this protection are unknown. Due to the strong
      overexpression of the pancreatitis-associated protein I during the climax of the
      acute phase, this protein might be involved in the defense mechanism.

PMID- 9590320
TI  - Exogenous interleukin-10 fails to decrease the mortality or morbidity of sepsis.
AB  - OBJECTIVE: To determine if exogenous interleukin (IL)-10 will decrease the
      morbidity or mortality of sepsis induced by cecal ligation and puncture. DESIGN:
      Prospective, randomized, controlled study. SETTING: University research
      laboratory. SUBJECTS: Adult, female, Balb?c mice. INTERVENTIONS: Balb?c mice were
      subjected to cecal ligation and puncture with an 18- or 23-gauge needle and
      treated with triple antibiotics. Mice were injected subcutaneously with
      recombinant human IL-10 (diluted in normal saline with 0.1% mouse serum albumin)
      and followed until death. In a separate experiment, IL-10 was also injected
      subcutaneously and lipopolysaccharide (LPS) injected intraperitoneally and plasma
      tumor necrosis factor concentrations measured 90 mins later. MEASUREMENTS AND
      MAIN RESULTS: In the LPS experiments, IL-10 decreased tumor necrosis factor (TNF)
      production by nearly 90%. For the cecal ligation and puncture experiments,
      temperature and movement were recorded continuously via implanted transmitters.
      Studies on mortality indicated that exogenous IL-10 given at 0, +6 and +12 hrs
      after surgery failed to increase survival when using an 18-gauge needle
      (alive:total cecal ligation and puncture alone 4:21; IL-10 10 microg/mouse 2:12;
      1 microg/mouse 8:25; 0.1 microg/mouse 1:12) or a 23-gauge needle (cecal ligation
      and puncture alone 13:29; IL-10 1 microg 18:30). There was no difference in the
      number of hours to death between the groups. IL-10 did not prevent the
      hypothermia after cecal ligation and puncture or increase the animals' activity.
      To examine parameters of inflammation, mice were killed 8 hrs after 18-gauge
      cecal ligation and puncture. IL-10 (1 microg/mL) failed to reduce pulmonary
      neutrophil sequestration (lung myeloperoxidase, cecal ligation and puncture 107
      +/- 10 [SEM], IL-10 107 +/- 5) or recruitment of neutrophils to the peritoneum
      (neutrophils x 10(6), cecal ligation and puncture 3.72 +/- 0.62; IL-10 3.49 +/-
      0.37). IL-10 also failed to reduce the appearance of TNF or IL-6 in the plasma or
      peritoneal fluid. The chemokine KC was reduced in the peritoneal fluid but not
      the plasma and endogenous IL-10 production was not reduced in the peritoneum.
      CONCLUSION: Our data indicate that exogenous IL-10 fails to improve morbidity or
      mortality in the clinically relevant cecal ligation and puncture model of sepsis.

PMID- 9590321
TI  - Aminoguanidine attenuates endotoxin-induced acute lung injury in rabbits.
AB  - OBJECTIVE: To assess the effect of aminoguanidine, a selective inducible nitric
      oxide synthase inhibitor, on endotoxin-induced acute lung injury in rabbits.
      DESIGN: Prospective, blinded, controlled laboratory study. SETTING: University
      research laboratory. SUBJECTS: Twenty-eight male rabbits. INTERVENTIONS: The
      animals were randomly assigned to receive one of four treatments (n = 7 for each
      group): infusion of saline only (S-S group), infusion of saline and
      aminoguanidine (S-AG group), infusion of Escherichia coli endotoxin (5 mg/kg over
      60 mins) (E-S group), and infusion of endotoxin and aminoguanidine (E-AG group).
      Fifteen minutes before infusion of endotoxin (E-S and E-AG groups) or saline (S-S
      and S-AG groups), the animals received an intravenous injection of 1 mg/kg of
      aminoguanidine (S-AG and E-AG groups) or saline (S-S and E-S groups). The same
      dose of aminoguanidine or saline was given 1 hr after the end of endotoxin or
      saline infusion. The lungs of the rabbits were ventilated with 40% oxygen.
      MEASUREMENTS AND MAIN RESULTS: Hemodynamics, peripheral leukocyte counts, and
      PaO2 were recorded during the ventilation period (6 hrs). After these
      observations were made, lung mechanics, cell fraction of bronchoalveolar lavage
      fluid, and concentrations of thromboxane A2 and prostacyclin metabolites in
      bronchoalveolar lavage fluid were determined. The wet weight/dry weight ratio of
      the lung and albumin concentrations in bronchoalveolar lavage fluid were analyzed
      as indices of pulmonary edema. Endotoxin decreased the lung compliance and PaO2
      and increased the wet weight/dry weight ratio, neutrophil counts, and albumin
      concentrations in bronchoalveolar lavage fluid. The bronchoalveolar lavage fluid
      concentrations of thromboxane B2 in bronchoalveolar lavage fluid were increased
      by infusion of endotoxin. Aminoguanidine attenuated these changes. Endotoxin
      caused extensive morphologic lung damage, which was lessened by aminoguanidine.
      CONCLUSIONS: Aminoguanidine given intravenously before and after endotoxin
      attenuated endotoxin-induced lung injury in rabbits. These findings suggest that
      inducible nitric oxide synthase inhibition may be useful in the treatment of
      endotoxin-induced lung injury. However, further studies are required to determine
      the optimal dosage of aminoguanidine, when the inhibitor is given alone as
      therapy after lung injury.

PMID- 9590322
TI  - A comparison among animal models of acute lung injury.
AB  - OBJECTIVES: To compare four widely used animal models of acute lung injury and to
      determine the changes in physiologic variables associated with each model.
      DESIGN: A prospective, controlled animal study. SETTING: An animal laboratory of
      a university-affiliated children's hospital. SUBJECTS: Four groups of
      anesthetized, paralyzed, and ventilated young Yorkshire pigs, weighing 35 to 45
      kg. INTERVENTIONS: Acute lung injury was generated by four different methods: a)
      intrapulmonary arterial infusion of endotoxin of Escherichia colt; b)
      bronchoalveolar instillation of 0.05N of hydrochloric acid; c) repeated
      bronchoalveolar warm saline lavage; and d) intrapulmonary arterial infusion of
      oleic acid. After each acute lung injury procedure, the temporal changes in
      various physiologic variables were measured, starting at 60 mins and at 15-min
      intervals thereafter for a total of 165 mins. Systemic and mixed venous serum
      immunoreactive tumor necrosis factor (TNF)-alpha concentrations were also
      measured at the same time points. Analysis of variance for repeated measures was
      employed to determine the absolute and relative significance of the changes
      observed. MEASUREMENTS AND MAIN RESULTS: Systemic and mixed venous immunoreactive
      TNF-alpha did not change following any of the acute lung injury procedures. The
      animals' heart rates and systemic vascular resistances also did not change.
      Hydrochloric acid instillation as well as bronchoalveolar lavage resulted in
      significant hypoxemia with no other hemodynamic effects. Endotoxin infusion did
      not result in hypoxemia but caused significant increases in mean pulmonary
      arterial pressure and pulmonary vascular resistance and decreases in mean
      arterial pressure and cardiac output. Oleic acid infusion resulted in a marked
      hypoxemia with a pronounced increase in mean pulmonary arterial pressure and
      pulmonary vascular resistance. It also markedly reduced the mean arterial
      pressure, cardiac output, and the mixed venous PO2. CONCLUSIONS: The surfactant
      depletion and hydrochloric acid instillation models produce acute hypoxemia in an
      otherwise hemodynamically stable animal. A brief endotoxin infusion provides a
      model for cardiovascular instability and pulmonary hypertension but fails to
      produce hypoxemia in the pig. The oleic acid infusion creates a model of marked
      cardiovascular instability, pulmonary hypertension, and profound hypoxemia.
      However, none of the acute lung injury models described was associated with the
      production of tumor necrosis factor.

PMID- 9590323
TI  - Altered release of prostaglandins by opioids contributes to impaired cerebral
      hemodynamics following brain injury.
AB  - OBJECTIVES: After fluid percussion brain injury (FPI) in the newborn pig, pial
      arteries constrict and responses to dilator stimuli, including opioids, are
      blunted. This study was designed to determine if altered release of
      prostaglandins contributes to blunted opioid dilation of cerebral arteries in
      newborn piglets following brain injury. DESIGN: Prospective, in vivo, cerebral
      hemodynamic animal study. SETTING: University research laboratory. SUBJECTS:
      Newborn (1- to 5-days old) piglets of either gender. INTERVENTIONS: In
      anesthetized, newborn, 1- to 5-day-old pigs, a closed cranial window was used to
      measure pial artery diameter and to collect cortical periarachnoid cerebrospinal
      fluid (CSF) for determination of 6-keto-PGF1alpha, the stable metabolite of
      prostaglandin I2 (PGI2) and thromboxane B2 (TXB2), the stable metabolite of TXA2,
      via radioimmunoassay. FPI of moderate severity (1.9 to 2.3 atmospheres) was
      produced by using a pendulum to strike a piston on a saline-filled cylinder that
      was fluid coupled to the brain via a hollow screw inserted through the cranium.
      MEASUREMENTS AND MAIN RESULTS: Methionine enkephalin (Met) vasodilation was
      blunted after FPI but was partially restored with indomethacin pretreatment (5
      mg/kg i.v.) (8 +/- 1 [SEM] %, 13 +/- 1%, and 20 +/- 1% vs. 1 +/- 1%, 3 +/- 1%,
      and 5 +/- 1% vs. 7 +/- 1%, 10 +/- 1%, and 15 +/- 1%, respectively, for 10(-10),
      10(-8), and 10(-6) M Met during control conditions, after FPI, and after FPI
      pretreated with indomethacin, n = 6). Similarly, restoration of Met dilation
      after FPI was observed with SQ 29,548, a TXA2 antagonist. Met-induced 6-keto
      PGF1alpha release was blunted following FPI (889 +/- 20, 1130 +/- 33, and 1886 +/
      59 vs. 2630 +/- 36, 2775 +/- 30, and 2825 +/- 36 pg/mL for control, 10(-10), and
      10(-6) M Met before and after FPI, respectively, n = 6). In contrast, Met-induced
      TXB2 release was enhanced after FPI (340 +/- 20, 423 +/- 25, and 473 +/- 30 pg/mL
      vs. 518 +/- 30, 726 +/- 90, and 901 +/- 35 pg/mL for control, 10(-10), and 10(-6)
      M Met before and after FPI, respectively, n = 6). Leucine enkephalin- and
      dynorphin-induced dilation and associated prostaglandin release were similarly
      altered following FPI. Beta endorphin-induced constriction was enhanced following
      FPI, and these potentiated responses were blunted after indomethacin or SQ 29,548
      pretreatment. CONCLUSIONS: These data show that FPI increases CSF 6-keto
      PGF1alpha and TXB2 concentrations. These data suggest that altered release of
      prostaglandins by opioids contribute to impaired cerebral hemodynamics following
      FPI in piglets.

PMID- 9590324
TI  - Left ventricular performance following the arterial switch operation: use of
      noninvasive wall stress analysis in the postoperative period.
AB  - OBJECTIVE: To determine postoperative left ventricular mechanics following the
      arterial switch operation (ASO). DESIGN: Prospective, cohort study. SETTING:
      Pediatric cardiac recovery room. PATIENTS: Nine neonates with transposition of
      the great arteries undergoing the ASO within the first week of life.
      INTERVENTIONS: Noninvasive ejection phase indices: shortening fraction (% SF),
      corrected mean velocity of circumferential shortening (VCFc), and wall stress
      analysis were used to calculate indices of specific left ventricular systolic
      mechanics. The % SF and VCFc were respectively adjusted for left ventricular
      afterload (end-systolic wall stress) to derive an index for left ventricular
      performance (stress-shortening relation) and contractility (stress-velocity
      relation). Left ventricular preload was assessed as the variance between the
      performance and contractility indices. All indexed data are reported as mean
      Zscore (i.e., number of standard deviations from the mean of a normal age- and
      body surface area-adjusted population). A mean Zscore of < -2 or > 2 was regarded
      as a significant variance from normal. Transmitral Doppler flow patterns were
      recorded at each postoperative interval and analyzed for isovolumic relaxation
      time (IVRT) as an index of left ventricular compliance. MEASUREMENTS AND MAIN
      RESULTS: All nine patients did well clinically and completed the study.
      Noninvasive parameters were measured at mean intervals of 3 (early), 23
      (intermediate), and 48 hrs (late postoperative) relative to the time of arrival
      in the cardiac recovery room. Postoperative left ventricular performance was
      decreased throughout the early (-4.0 +/- 1.5 SD), intermediate (-4.1 +/- 2.8),
      and late (-3.5 +/- 1.3) phases of recovery. In contrast, the overall left
      ventricular contractility remained normal throughout the three postoperative
      intervals (0.2 +/- 1.8, -1.2 +/- 1.9, and -1.0 +/- 1.6, respectively), although
      three of the nine patients had a diminished stress-velocity index during the
      study period. Left ventricular afterload was within normal range in the early
      (0.1 +/- 1.7) and intermediate (1.5 +/- 1.9) phases of recovery, but increased in
      the late postoperative period (2.5 +/- 2.9). Left ventricular preload was
      decreased significantly throughout the early (-4.2 +/- 1.3), intermediate (-2.8
      +/- 2.0), and late (-2.5 +/- 1.0) postoperative phases. All nine patients
      demonstrated decreased preload during the recovery period. IVRT was decreased in
      the post-ASO patients at each phase of recovery compared with normal data (p <
      .001). CONCLUSIONS: Left ventricular performance is impaired in infants during
      the period immediately following the ASO. A persistent preload deficit closely
      matches the pattern of impaired ventricular performance. Decreased IVRT points to
      impaired ventricular compliance as the etiology of the altered preload. In
      contrast, left ventricular contractility remains normal in the majority of post
      ASO patients. Decreased contractility may account for impaired ventricular
      performance in selected cases.

PMID- 9590325
TI  - Increased circulating thrombomodulin in children with septic shock.
AB  - OBJECTIVES: To test the hypothesis that children diagnosed with septic shock have
      increased plasma thrombomodulin values as a manifestation of microcirculatory
      dysfunction and endothelial injury; to determine whether plasma thrombomodulin
      concentrations are associated with the extent of multiple organ system failure
      and mortality. DESIGN: Prospective, cohort study. SETTING: Pediatric intensive
      care unit. PATIENTS: Twenty-two children with septic shock and ten, healthy,
      control children. INTERVENTIONS: Blood samples were obtained for plasma
      thrombomodulin determinations every 6 hrs for 72 hrs in septic shock patients and
      once in healthy control patients. MEASUREMENTS AND MAIN RESULTS: Thirty-two
      children (22 septic shock, and 10 healthy controls) were enrolled in the study.
      Thrombomodulin concentrations were determined by an enzyme-linked immunosorbent
      assay. Septic shock nonsurvivors had significantly greater mean thrombomodulin
      concentrations (10.6 +/- 2.2 ng/mL) than septic shock survivors (5.5 +/- 0.6
      ng/mL) (p < .05) and healthy control patients (3.4 +/- 0.2 ng/mL) (p < .01). Mean
      thrombomodulin values increased as the number of organ system failures increased.
      CONCLUSIONS: Pediatric survivors and nonsurvivors of septic shock have
      circulating thrombomodulin concentrations 1.5 and 3 times greater than healthy
      control patients. These findings likely represent sepsis-induced endothelial
      injury. Patients with multiple organ system failure have circulating
      thrombomodulin concentrations which are associated with the extent of organ
      dysfunction. We speculate that measurement of plasma thrombomodulin
      concentrations in septic shock may be a useful indicator of the severity of
      endothelial damage and the development of multiple organ system failure.

PMID- 9590326
TI  - Expiratory phase and volume-adjusted tracheal gas insufflation: a lung model
      study.
AB  - OBJECTIVE: To evaluate in a lung model the effects of expiratory-phase tracheal
      gas insufflation (expiratory-phase TGI) with both volume and pressure control
      ventilation, and tidal volume-adjusted continuous flow TGI (volume-adjusted TGI)
      on system pressures and volumes. DESIGN: Single-compartment lung model. SETTING:
      Research laboratory in a university medical center. INTERVENTIONS: Expiratory
      phase TGI was established, using a solenoid valve activated by the ventilator.
      Volume-adjusted TGI was applied by reducing tidal volume (VT) by the product of
      TGI flow and inspiratory time. Ventilation was provided with pressure control of
      20 cm H2O or volume control ventilation with VT similar to that with pressure
      control ventilation. A rate of 15 breaths/min and positive end-expiratory
      pressure (PEEP) of 10 cm H2O were used throughout. Inspiratory time periods of
      1.0, 1.5, 2.0, and 2.5 secs were used with TGI flows of 0, 4, 8, and 12 L/min.
      Lung model compliance (mL/cm H2O) and resistance (cm H2O/L/sec) combinations of
      20/20, 20/5, and 50/20 were used. MEASUREMENTS AND MAIN RESULTS: In expiratory
      phase TGI with pressure control ventilation, peak alveolar pressure remained
      constant, PEEP increased (p < .01) and VT decreased (p < .01). In expiratory
      phase TGI with volume control ventilation and volume-adjusted TGI, there were
      significant increases in peak alveolar pressure and PEEP (p < .01). Readjustment
      of VT in volume-adjusted TGI was impossible with longer inspiratory time (> or =
      2 secs) and higher TGI flows (> or = 8 L/min). CONCLUSIONS: The marked increases
      in system pressures and volumes observed with continuous-flow TGI can be avoided
      with expiratory-phase TGI and volume-adjusted TGI.

PMID- 9590327
TI  - Complications of sedation with midazolam in the intensive care unit and a
      comparison with other sedative regimens.
AB  - OBJECTIVE: To describe the various complications that have been reported with use
      of midazolam for sedation in the intensive care unit (ICU). DATA SOURCES:
      Publications in scientific literature. DATA EXTRACTION: Computer search of the
      literature. SYNTHESIS: Sedation is required in the ICU in order for patients to
      tolerate noxious stimuli, particularly mechanical ventilation. Under- and
      oversedation can lead to complications. To sedate patients in the ICU, midazolam
      is commonly administered via titrated, continuous infusions. Cardiorespiratory
      effects tend to be minimal; however, hypotension can occur in hypovolemic
      patients. Prolonged sedation after cessation of the midazolam infusion may be
      caused by altered kinetics of the drug in critically ill patients or by
      accumulation of active metabolites. In addition, paradoxical and psychotic
      reactions have been rarely reported. Tolerance and tachyphylaxis may occur,
      particularly with longer-term infusions (> or = 3 days). Benzodiazepine
      withdrawal syndrome has also been associated with high dose/long-term midazolam
      infusions. Compared with propofol infusions, midazolam infusions have been
      associated with a decreased occurrence of hypotension but a more variable time
      course for recovery of function after the cessation of the infusion. Lorazepam is
      a more cost-effective choice for long-term (> 24 hrs) sedation. CONCLUSION:
      Continuous infusion midazolam provides effective sedation in the ICU with few
      complications overall, especially when the dose is titrated.

PMID- 9590328
TI  - Portable devices used to detect endotracheal intubation during emergency
      situations: a review.
AB  - OBJECTIVES: To review the operational characteristics of commercial devices used
      to detect endotracheal intubation; and to identify an ideal device for detecting
      endotracheal intubation in emergency situations, especially in the prehospital
      setting during cardiac arrest. DATA SOURCES: Relevant articles from the medical
      literature are referenced. STUDY SELECTION: The authors identified the need for
      understanding the basic operation principles of portable devices used to detect
      endotracheal intubation and to correctly use them in unpredictable clinical
      situations. DATA EXTRACTION: Data from published literature. DATA SYNTHESIS:
      Recently, a number of new portable devices have been marketed for detecting
      endotracheal intubation, each having advantages and disadvantages, especially
      when used during emergency situations. The devices are classified based on their
      principle of operation. Some rely on CO2 detection (STATCAP, Easy Cap, and Pedi
      Cap), others utilize the transmission of light (Trachlight, SURCH-LITE), one
      operates based on reflection of sound energy (SCOTI), and some depend on
      aspiration of air (TubeChek and TubeChek-B). A brief description of each device
      and its operational characteristics are reviewed. A comparative analysis among
      the devices is made based on size, portability, cost, ease of operation, need for
      calibration or regular maintenance, reliability for patients with and without
      cardiac arrest, and the possibility of use for adult and pediatric patients.
      False-negative and false-positive results for each device are also discussed.
      False-negative results mean that although the endotracheal tube is in the
      trachea, the device indicates it is not. False-positive results mean that
      although the endotracheal tube is in the esophagus, the device indicates it is in
      the trachea. CONCLUSIONS: Although no clinical comparative study of commercial
      devices to detect endotracheal intubation exists, the syringe device (TubeChek)
      has most of the characteristics necessary for a device to be considered ideal in
      emergency situations in the prehospital setting. It is simple, inexpensive, easy
      to handle and operate, disposable, does not require maintenance, gives reliable
      results for patients with and without cardiac arrest, and can be used for almost
      all age groups. The device may yield false-negative results, most commonly in the
      presence of copious secretions and in cases of accidental endobronchial
      intubation. Regardless of the device used, clinical judgment and direct
      visualization of the endotracheal tube in the trachea are required to
      unequivocally confirm proper endotracheal tube placement.

PMID- 9590329
TI  - Protein C in the treatment of coagulopathy in meningococcal disease.
AB  - OBJECTIVE: To evaluate the clinical and laboratory effects of the substitution of
      protein C (PC) as an adjunct to conventional therapy in the treatment of purpura
      fulminans associated with meningococcal sepsis. DESIGN: case series. SETTING:
      Medical and medical-surgical intensive care units of two university hospitals.
      PATIENTS: Three patients with purpura fulminans and multiple organ failure caused
      by Neisseria meningitidis. INTERVENTION: Intravenous administration of PC
      concentrate (100 IU/kg every 6 to 8 hrs). MEASUREMENTS AND MAIN RESULTS: The
      administration of PC resulted in normal or above normal levels of the plasma PC
      activity in all patients. The laboratory and clinical parameters reflecting the
      severity of coagulopathy improved during the treatment, as did peripheral
      ischemia and the clinical manifestations of multiple organ failure. No adverse
      events were noted. One patient died of cerebral edema. CONCLUSION: The
      administration of PC had a beneficial effect on coagulopathy and peripheral
      gangrene formation associated with meningococcal disease and showed no adverse
      effects.

PMID- 9590330
TI  - Recombinant tissue plasminogen activator restores perfusion in meningococcal
      purpura fulminans.

PMID- 9590331
TI  - Recombinant tissue plasminogen activator restores perfusion in meningococcal
      purpura fulminans.

PMID- 9590332
TI  - Recombinant tissue plasminogen activator restores perfusion in meningococcal
      purpura fulminans.

PMID- 9590333
TI  - The changing role of surgical care.

PMID- 9590334
TI  - Correlation of inflammatory cytokines with arthroscopic findings in patients with
      temporomandibular joint internal derangements.
AB  - PURPOSE: The goal of this study was to evaluate the presence of the inflammatory
      cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor
      necrosis factor-alpha (TNF-alpha) within the superior temporomandibular joint
      (TMJ) space in patients with internal derangements and to compare these values
      with the pathologic findings seen arthroscopically. PATIENTS AND METHODS: Thirty
      patients with symptomatic TMJ dysfunction and clinical and imaging evidence of
      internal derangements of the TMJ were evaluated. Before entering the superior
      joint space with the arthroscope, 2 mL sterile saline was injected and, after 30
      seconds of equilibration, was aspirated for analysis. The surgeon then performed
      diagnostic arthroscopy. The degree of synovitis, degeneration, percent condylar
      roofing, and any pathologic changes, such as perforations, were recorded. The
      level of total protein in each sample was ascertained, as well as the levels of
      IL-1 beta, IL-6, and TNF-alpha. RESULTS: Of 30 samples tested, three were
      discarded because of failure to gain access into the superior joint space. Of the
      27 remaining samples, IL-6 showed the closest correlation with the level of acute
      synovitis demonstrated arthroscopically. Two of the higher IL-6 levels (167 and
      324 pg/microg protein) were seen with patients with a significant disc
      perforation. In patients with a high degree of vascularity, IL-6 was found to be
      between 0 to 581 pg/microg protein with an average of 80 pg/microg protein and a
      median value of 43 pg/mg. These values significantly correlated with the degree
      of vascularity (P < or = .02). This is in comparison with the 10 remaining
      patients, who showed significantly fewer vascular changes arthroscopically. In
      these patients, the range of IL-6 was 0 to 35 pg/microg protein, with an average
      of 19 pg/microg protein and a median value of 14.5 pg/microg. These values
      significantly correlated with the smaller degree of vascularity (P < or = .02).
      In seven patients, the role of nonsteroidal antiinflammatory drug (NSAID) use
      resulted in decreased levels of IL-6, which has been noted in previous studies.
      In patients with higher rated redundancy of the synovial tissue, the average IL-6
      level was 92 pg/microg protein, whereas the median value was 44 pg/microg
      protein. In patients with little or no redundant synovial tissue, an average IL-6
      level of 22 pg/microg protein was present. The median value in these same joints
      was 15 pg/microg protein. These IL-6 values significantly correlated with the
      degree of redundancy (P < or = .03). The degree of degenerative change
      (chondromalacia, fibrillation), disc displacement (roofing), and the presence or
      absence of adhesions did not significantly affect the levels of IL-6 within the
      patients studied. The presence of IL-1 beta and TNF-alpha was not found to
      correlate with the arthroscopic findings in the superior joint space.
      CONCLUSIONS: The presence of IL-6 correlated with the degree of acute synovitis.
      IL-1 beta and TNF-alpha were not found in significant levels within the superior
      joint space. These findings correlated with those reported by other
      investigators. The production of IL-6 by synovial cells and its role in TMJ
      disease warrants further investigation.

PMID- 9590335
TI  - Trigeminal neuropathy: improved imaging with a dental computed tomography
      software program.
AB  - PURPOSE: This study evaluated the use of images obtained by a dental computed
      tomography (CT) software program in the diagnosis and treatment of trigeminal
      neuropathy associated with jaw abnormality. PATIENTS AND METHODS: Twelve patients
      with jaw abnormality associated with trigeminal neuropathy as the presenting
      symptom were studied by plain film radiography (PFR) and by a dental CT software
      program (DS) that displays multiple panoramic and cross-sectional views of the
      mandible and maxilla. The two modalities were compared for delineation of the
      integrity of mandibular foramen, mandibular canal, mental foramen, incisive
      foramen, and incisive canal. Also, displacement of the neurovascular bundle was
      evaluated and scored. RESULTS: The DS was superior to PFR in showing the bony
      integrity of the foramina and canals in the jaws, as well as the degree of
      displacement of the neurovascular bundle. CONCLUSION: DS should be the study of
      choice for evaluating trigeminal neuropathy associated with abnormalities of the
      jaws.

PMID- 9590336
TI  - Augmentation genioplasty with hard tissue replacement implants.
AB  - PURPOSE: This study assessed the soft tissue changes produced by the placement of
      hard tissue replacement (HTR) polymer chin implants for augmentation genioplasty
      and evaluated the dimensional stability as well as any bony changes associated
      with the implants. PATIENTS AND METHODS: The study group consisted of 18 patients
      (3 males, 15 females) with an average follow-up of 21.5 months (range, 12 to 44
      months). All implants were placed through an intraoral incision and stabilized to
      the symphysis with a single 2.0-mm diameter titanium screw. Preoperative,
      postoperative, and long-term cephalometric radiographs were analyzed for changes
      in soft tissue thickness in the chin region, implant stability, and the presence
      of bone resorption. RESULTS: The net hard tissue chin augmentation achieved
      averaged 6.0 mm (range, 4.5 to 9 mm). Average preoperative soft tissue thickness
      was 12.1 mm (range, 11 to 14.5 mm) and postoperatively it was 10.6 mm (range, 10
      to 13.5 mm). The average increase in soft tissue projection was 77.6% (range,
      71.4% to 83.3%) of the implant thickness. There was no radiographic evidence of
      implant migration or bony resorption beneath the implant. CONCLUSIONS: HTR
      implants appear to be a predictable means of augmenting the chin, providing the
      desired aesthetic change, without causing resorption of underlying bone.

PMID- 9590337
TI  - Open reduction without fixation of dislocated condylar process fractures: long
      term clinical and radiologic analysis.
AB  - PURPOSE: This study evaluates the long-term results of open reduction without
      fixation for displaced fractures of the condylar process. PATIENTS AND METHODS:
      Clinical and radiologic examinations were performed on 27 patients with 29
      operated joints an average of 6.7 years postoperatively. The postoperative result
      was evaluated on the basis of occlusal and joint function, as well as
      radiographic assessment of condylar changes. RESULTS: Clinically, satisfactory
      results were achieved. Radiologically, despite correct intraoperative alignment
      of the fractured segments, a slight medial deviation of the condylar process was
      found on the posteroanterior radiograph. However, in only two cases was a 20
      degree deviation observed. On final follow-up, 48% of the cases had a normal
      condylar configuration radiologically, and in the remaining cases, normal
      function was established even though there were condylar changes. Fully exposed
      and devascularized condylar processes generally showed more severe changes than
      those in which partial vascularization was maintained. CONCLUSION: The surgical
      management described enables a satisfactory outcome to be achieved with
      dislocated condylar process fractures.

PMID- 9590338
TI  - An intraoral approach to treatment of condylar hyperplasia or high condylar
      process fractures using the intraoral vertico-sagittal ramus osteotomy.
AB  - PURPOSE: The intraoral vertico-sagittal ramus osteotomy (J Craniomaxillofac Surg
      20:153, 1992) can be used to reduce high condylar process fractures and recontour
      hyperplastic condyles while simultaneously correcting the malocclusion. This
      article presents the technique and reports the clinical results. PATIENTS AND
      METHODS: A technique for removal and replantation of the condyloid process using
      the vertico-sagittal ramus osteotomy and rigid fixation was used to treat 23
      patients with markedly displaced, high condylar process fractures and condylar
      hyperplasia associated with malocclusion. RESULTS: The replanted condyles did not
      show ischemic necrosis or any functional disturbance when followed for more than
      3 years. All patients showed nearly normal mouth opening, with slight mandibular
      deviation, usually in sixth postoperative month. CONCLUSIONS: In selected
      patients, this technique allows intraoral accessibility to the condyle and its
      repositioning. The method is particularly useful to treat vertical discrepancies
      associated with the hyperplastic or hypoplastic condyle.

PMID- 9590339
TI  - Outpatient oral and maxillofacial surgery: transition to a Surgicenter setting
      and outcome of the first 200 cases.
AB  - Advances in techniques for perioperative management have reduced the morbidity
      associated with major oral and maxillofacial surgery. Simultaneously, pressures
      for cost control have affected patient access to surgical services. This report
      details the steps undertaken to effect a transition of major maxillofacial
      surgical procedures to an outpatient setting. Protocols for surgical, anesthetic,
      and postoperative management are described. Treatment outcomes for the first 200
      cases are reported. Only 1% of cases required subsequent inpatient care and a
      less than 1% major revision rate was experienced.

PMID- 9590340
TI  - A surgical approach to extensive tumors in the pterygopalatine fossa extending
      into the maxillary sinus.
AB  - PURPOSE: This article describes a surgical approach to extensive tumors in the
      pterygopalatine fossa extending into the maxillary sinus. TECHNIQUE: The Barbosa
      approach was modified by adding a lateral incision in the mandibular
      gingivobuccal fold from the canine tooth to the retromolar area. RESULTS: This
      technique allowed a large, inferiorly based flap to be raised, which includes the
      parotid gland. The masseter and temporalis muscles was divided horizontally, and
      the ascending ramus of the mandible was osteotomized between the mandibular angle
      and the sigmoid notch and reflected to expose the tumor in the pterygopalatine
      fossa and maxillary sinus. CONCLUSION: This technique is especially useful to
      tumors in the pterygopalatine fossa extending into the maxillary sinus.

PMID- 9590341
TI  - Criteria for diagnosing lymph node metastasis from squamous cell carcinoma of the
      oral cavity: a study of the relationship between computed tomographic and
      histologic findings and outcome.
AB  - PURPOSE: This retrospective study was conducted to determine the relationship
      between the computed tomographic findings for cervical lymph nodes (LN),
      histologic findings, and outcome in patients with squamous cell carcinoma of the
      oral cavity who underwent radical neck dissection. PATIENTS AND MATERIALS: Sixty
      six patients were analyzed. Of these 66 operations, 43 were immediate therapeutic
      dissections in clinically N+ necks, and 23 were subsequent therapeutic
      dissections in patients whose necks were initially node free but progressed to
      positive nodes during observation. RESULTS: When the size criterion (area of the
      axial section) of nodal metastasis depicted on the scan of 45 mm2 was selected,
      almost 78% of LN were diagnosed consistent with the histologic diagnosis. As the
      size of the LN increased, the frequency of extranodal invasion also became
      higher, whereas patients with the higher histologic grades of malignancy often
      showed neck metastases with extranodal invasion in the early stage. Patients
      having LN smaller than 100 mm2, or without extranodal invasion, showed good
      outcome, whereas those having LN 100 mm2 or larger, with extranodal invasion,
      showed extremely poor outcome. CONCLUSIONS: These findings indicate that it is
      possible to delay neck dissection in node-free patients until neck disease is
      diagnosed with timely CT examination, although great caution is necessary,
      especially in those with a high histologic grade of malignancy.

PMID- 9590342
TI  - The influence of craniofacial structure on obstructive sleep apnea in young
      adults.
AB  - PURPOSE: This study compares craniofacial measurements of lateral cephalometric
      radiographs of young obstructive sleep apnea patients with those of nonapneic
      snorers and controls. PATIENTS AND METHODS: Forty-eight patients (BM=28.0+/-3.8)
      with obstructive sleep apnea, 25 patients (BMI=26.3+/-3.5) with nonapneic
      snoring, and 54 controls (BMI=24.8+/-2.7) were evaluated. All subjects were
      between 18 and 40 years of age. Nineteen lateral cephalometric measurements were
      performed by a single investigator blinded to the results of the polysomnograms.
      RESULTS: Univariate logistic regression analysis of the 19 variables showed
      significantly increased midfacial height (ANS-N), narrowed middle airway space
      (MAS), steep mandibular plane angle (FMA), elongated pharynx (PNS-Eb), and
      inferiorly positioned hyoid bone (PNS-H, MP-H) in the obstructive sleep apnea
      group. The nonapneic snoring group showed only a tendency toward maxillary and
      mandibular retrognathia (SNA and SNB). No significant differences were found for
      cranial base angle (S-N-Ba), PAS, inferior airway space, maxillary unit length
      (ANS-PNS) mandibular unit length (Cd-Gn), tongue height (Tng-Ht), soft palate
      length (PNS-P), and palatal vault height (Ocl-Pal 6). The OSA group was also
      found to have multiple sites of abnormality of both the upper and lower pharynx,
      with 58% of the patients having two or more abnormal values (1 standard deviation
      from the mean) as opposed to 40% of the nonapneic snoring group. CONCLUSIONS:
      Highly significant craniofacial abnormalities were found in the upper and lower
      pharynx in young obstructive sleep apnea patients. Most of these patients (58%)
      had abnormalities in both the upper and lower pharynx, suggesting that palatal
      surgery alone may be an inadequate treatment. This information may define future
      investigations needed to determine how to more effectively treat this subgroup of
      young obstructive sleep apnea patients.

PMID- 9590343
TI  - A 5-year in vitro and in vivo study of the biodegradation of polylactide plates.
AB  - PURPOSE: The purpose of this study was to investigate the long-term tissue
      response and duration of degradation of self-reinforced poly-L-lactide (SR-PLLA)
      multilayer plates in vivo. MATERIALS AND METHODS: Mandibular osteotomies in sheep
      were fixed with SR-PLLA multilayer plates. The animals were followed for 1, 2, 3,
      4, and 5 years, after which histologic studies were performed. RESULTS: The
      foreign-body reaction was mainly mild, and the osteotomies were well united.
      After 5 years in vivo, the material was almost completely resorbed, but small
      particles of polymer could still be detected at the implantation site. SR-PLLA
      plates were also incubated in vitro for 5 years. The material degraded
      considerably faster in vivo than in vitro. Molecular weight, melting temperature,
      and crystallinity of the plates remained at a constant level after 2 years in
      vitro, indicating very slow degradation of the oligomeric (molecular weight [Mw],
      3500 daltons), highly crystalline (heat of fusion, 70 J/g), PLLA residue solely
      as a result of hydrolysis. Although the plates became increasingly fragile as
      they degraded, they retained their macroscopic form until the end of the 5-year
      follow-up. Loss of mass of the plates was 52%+/-8% after 5 years of incubation in
      vitro. CONCLUSIONS: Although the long degradation period may seem to be a minor
      drawback to the use of such plates, it does not appear to affect the healing
      process.

PMID- 9590344
TI  - Experimental reconstruction of the mandible using polylactic acid tubes and basic
      fibroblast growth factor in alloplastic scaffolds.
AB  - PURPOSE: This study evaluated the use of a mitogenic growth factor in combination
      with barrier membranes and porous alloplastic scaffolds for the repair of
      segmental defects of the mandible. MATERIALS AND METHODS: Fifteen Gottingen
      minipigs were used for the study. In five animals, mandibular defects of 2 cm
      were created on both sides of the mandible and bridged by a system of polylactic
      acid (PLA) tubes and pyrolized bovine bone. On one side of the mandible, the
      alloplastic scaffolds were loaded with 115 microg recombinant human basic
      fibroblast growth factor (rhbFGF). In five other animals, defects 4 cm in length
      were created bilaterally, similarly bridged, and loaded with 230 microg of rhFGF.
      In five control animals, bilateral 2-cm defects were created that were left empty
      on one side and bridged with an empty PLA tube on the other. Mitogenic efficacy
      of the growth factor was assessed on fibroblast cultures by di-methyl-thiazol-2
      tetrazolium-bromide assay before implantation. RESULTS: After 5 months, there was
      negligible bone regeneration in the control defects, regardless of whether they
      had been left completely empty or bridged by empty PLA tubes. The 2-cm defects
      showed bridging in 8 of 10 tubes, with complete consolidation by bone ingrowth in
      four defects. The 4-cm defects showed bony union in six cases, with complete bone
      fill in two tubes, and four defects incompletely filled. The bFGF had no
      appreciable effect with regard to velocity, quantity, and three-dimensional
      structure of bone formation, neither in the short nor in the long defects despite
      clear in vitro efficacy. CONCLUSION: Repair of segmental defects using
      bioresorbable membranes appears to be possible. However, a single-dose
      application of bFGF is apparently ineffective, possibly because of rapid
      dilution.

PMID- 9590345
TI  - Surgical correction of mandibular hypoplasia in hemifacial microsomia: the case
      for treatment in early childhood.

PMID- 9590346
TI  - Surgical correction of mandibular hypoplasia in hemifacial microsomia: a personal
      perspective.

PMID- 9590347
TI  - Current concepts in the pathogenesis and treatment of acne.

PMID- 9590348
TI  - Mildly symptomatic radiolucency of the mandible.

PMID- 9590349
TI  - Liposarcoma of the cheek: report of a case.

PMID- 9590350
TI  - Submental osseous choristoma: a case report.

PMID- 9590351
TI  - Sinonasal lymphoma presenting as a lethal midline granuloma: case report.

PMID- 9590352
TI  - Ameloblastic fibrosarcoma of the maxilla: report of a case.

PMID- 9590353
TI  - Pneumoparotid: report of a case.

PMID- 9590354
TI  - The current status of percutaneous dilational tracheostomy: an alternative to
      open tracheostomy.

PMID- 9590355
TI  - A simple, atraumatic technique for the dissection of nasal mucosa during Le Fort
      I osteotomy.

PMID- 9590356
TI  - Distinguishing calcium pyrophosphate dihydrate deposition disease from synovial
      chondrosarcoma.

PMID- 9590357
TI  - First report of a granular cell tumor in a fetus.

PMID- 9590358
TI  - On the measurement of cholecystokinin.

PMID- 9590359
TI  - Low serum creatine kinase activity.

PMID- 9590360
TI  - Rapid capillary zone electrophoresis in isoelectric histidine buffer: high
      resolution of the poly-T tract allelic variants in intron 8 of the CFTR gene.
AB  - The poly-T tract in intron 8 of the cystic fibrosis conductance transmembrane
      regulator (CFTR) gene exists in three variants, 5T, 7T, and 9T. The 7T and 9T
      variants generate a predominantly normal transcript, whereas the 5T variant
      engenders an anomalous product. The analysis of the poly-T tract is assuming
      increasing relevance, both to assess the implication of the CFTR gene in
      congenital bilateral absence of the vas deferens and to evaluate genotype
      phenotype correlation in cystic fibrosis. Mapping of the poly-T tract has been
      performed by cumbersome and time-consuming methodologies. Capillary zone
      electrophoresis, combined with laser-induced fluorescence detection, was
      introduced for a rapid separation of the poly-T tract amplified products. As
      separation buffer, we adopted 200 mmol/L histidine (pH = pI = 7.6), and the
      capillary was filled with 10% polyacrylamide, allowing separations in less than
      10 min. Capillary zone electrophoresis results were in perfect agreement with dot
      blot analysis.

PMID- 9590361
TI  - Ultrarapid drug metabolism: PCR-based detection of CYP2D6 gene duplication.
AB  - The enzyme debrisoquine 4-hydroxylase (CYP2D6), which metabolizes many widely
      used drugs, is highly polymorphic. The activity of the enzyme ranges between
      subjects from ultrafast to a complete absence. Therefore, metabolic capacity
      varies, producing intersubject differences in therapeutic efficacy and side
      effects at standard recommended doses. Up to 7% of Caucasians may demonstrate
      ultrarapid drug metabolism (UM) because of inherited alleles with multiplicate
      functional CYP2D6 genes, causing an increased amount of enzyme to be expressed.
      Identification of UM subjects is of potential clinical importance for adjustment
      of doses in drug therapy, as well as to avoid misidentification of noncompliance.
      In our study, we tested recently designed PCR assays for the detection of the UM
      genotype. We found a 3.5% prevalence of UMs carrying duplicate active CYP2D6
      genes in a population consisting of 202 psychiatric patients.

PMID- 9590362
TI  - A homogeneous fluorescence assay for PCR amplicons: its application to real-time,
      single-tube genotyping.
AB  - We have developed a method whereby a single TaqMan probe can be used for many PCR
      reactions. We demonstrate its application as an integrated system for the direct
      measurement of allele-specific amplicon generation coupled to the suppression of
      primer-dimer accumulation in PCR. The system uses a 5'-exonuclease assay of
      amplicon annealed fluorogenic probes that operates in conjunction with the
      Amplification Refractory Mutation System, whereby relative changes in reporter
      fluorescent emission are monitored in real-time using an analytical thermal
      cycler. We have called this system Three-STAR, and it is universal in that it can
      either use a single probe for the detection of any one target DNA sequence or a
      single pair of probes for genotyping any bi-allelic polymorphism. Three-STAR is,
      therefore, particularly useful for the single-tube genotype analysis of a variety
      of human DNA polymorphisms and mutations.

PMID- 9590363
TI  - Antioxidant enzymes and fatty acid status in erythrocytes of Down's syndrome
      patients.
AB  - The excess of genetic information in patients with Down's syndrome (DS) produces
      an increase in the catalytic activity of superoxide dismutase (SOD1), an
      antioxidant enzyme coded on chromosome 21. It has been suggested that an increase
      in oxidative stress in DS patients may cause adverse effects in the cell
      membranes through the oxidation of polyunsaturated fatty acids (PUFAs). The aim
      of this study was to evaluate the cellular antioxidant system by determining the
      catalytic activity of the SOD1, glutathione peroxidase (GPx), catalase (CAT), and
      glutathione reductase (GR) enzymes and the concentrations of alpha-tocopherol in
      red blood cells (RBCs) in a group of 72 DS patients. The profile of fatty acids
      in the phospholipids of RBC membranes was also evaluated. The activity of the
      erythrocyte antioxidant enzymes is significantly higher in the DS group than in
      the control group (SOD1, 635 +/- 70 U/g Hb vs 476 +/- 67 U/g Hb; CAT, 1843 +/-
      250 U/g Hb vs 1482 +/- 250 U/g Hb; GPx, 23.2 +/- 5.3 U/g Hb vs 21.5 +/- 3.6 U/g
      Hb; and GR, 9.32 +/- 1.4 U/g Hb vs 6.9 +/- 1.3 U/g Hb, respectively). No
      differences were observed in RBC alpha-tocopherol concentrations between the two
      groups studied. Long-chain n6 PUFA (C20:3n6, C20:4n6) concentrations were
      increased in DS patients, suggesting enhanced delta-6-desaturase activity. The
      long-chain n3 PUFA (docosahexenoic acid) does not appear to be affected by
      increased oxidative stress, probably because of the existence of compensatory
      antioxidant mechanisms.

PMID- 9590364
TI  - Cardiac troponin T in patients with end-stage renal disease: absence of
      expression in truncal skeletal muscle.
AB  - In patients with end-stage renal disease (ESRD), the serum concentration of
      cardiac troponin T (cTnT) may be increased without cardiac ischemia. One reason
      for this unexplained increase could be the extracardiac expression of cTnT.
      However, truncal skeletal muscle biopsies of five patients with ESRD showed no
      evidence of the expression of either cTnT mRNA (reverse transcription-PCR) or
      protein (immunoblot, immunofluorescence). We also measured the serum
      concentration of cTnT in 97 patients with ESRD. The serum cTnT concentration
      determined in both first and second generation cTnT assays was significantly
      lower P <0.01 in patients with a low cardiac risk than in patients with positive
      indicators of coronary artery disease. The correlation between cTnT and
      indicators of coronary artery disease is consistent with the hypothesis that cTnT
      in the serum of patients with ESRD originates from the heart.

PMID- 9590365
TI  - Serum creatine kinase activity is not a reliable marker for muscle damage in
      conditions associated with low extracellular glutathione concentration.
AB  - Creatine kinase (CK, EC 2.7.3.2) assays usually contain thiol-reducing compounds
      to restore the enzyme activity. In this study, we investigated the effect of
      endogenous extracellular glutathione on serum CK activity. We examined CK
      activity and glutathione concentrations in serum from 200 healthy subjects (107
      males, 93 females) and 38 patients with multiple organ failure, muscle wasting,
      and low serum CK activity (<50 U/L) (24 males, 14 females). Muscle damage was
      further evaluated using serum myoglobin concentrations and aldolase activity. In
      the overall group, serum glutathione concentrations correlated with serum CK
      activity (r = 0.791) but not with myoglobin concentrations and aldolase activity.
      In patients with multiple organ failure, low serum CK activities were accompanied
      by extremely low serum glutathione concentrations (<0.5 ,micromol/L, P <0.001).
      Endogenous glutathione can be regarded as a CK-preserving agent during the
      lifetime of the enzyme in the circulation (22 h on average). Serum CK activity
      should be interpreted with caution in patients with liver disease and multiple
      organ failure. In these conditions, the loss of CK activity due to extracellular
      glutathione depletion cannot be restored by the presence of thiol-reducing
      compounds in the CK assays.

PMID- 9590366
TI  - Serum protein electrophoresis and immunofixation by a semiautomated
      electrophoresis system.
AB  - Semiautomated agarose electrophoresis and immunofixation performed with Hydrasys
      Hyrys (Sebia) were compared with conventional, manually performed methods,
      including cellulose acetate electrophoresis, immunoelectrophoresis, and
      immunofixation. Reference intervals for agarose electrophoresis with Hydrasys
      Hyrys were determined. Within-run imprecision (CV) for fraction quantitation with
      the semiautomated system was between 1% (albumin) and 4.5% (beta-globulin). Total
      imprecision (CV) was between 2.7% (albumin) and 7.3% (beta-globulin).
      Semiautomated agarose electrophoresis showed linear correlation with cellulose
      acetate electrophoresis. Thirty-four specimens with monoclonal components were
      analyzed by manual immunoelectrophoresis and immunofixation and by Hydrasys. In
      one case, a light-chain disease was missed with Hydrasys when the sample was
      diluted 1:3 (the routine dilution) but not when the sample was assayed undiluted.
      In another case, the Hydrasys system revealed a small IgGA monoclonal component
      in addition to the IgA monoclonal component detected by the manual methods. In
      the other cases, no differences between the manual methods and the semiautomated
      method were seen with respect to paraprotein identification.

PMID- 9590367
TI  - Urinary measurement of transforming growth factor-beta and type IV collagen as
      new markers of renal injury: application in diabetic nephropathy.
AB  - Urinary samples were concentrated rapidly and efficiently and were used to
      develop several protein assays that may be of value in monitoring individuals
      with progressive renal disorders. Transforming growth factor-beta1 (TGF-11) and
      retinol binding protein (RBP) were measured with modification of commercially
      available methods used to assay serum specimens; type 3 collagen (T3C) was
      measured with a new immunonephelometric assay. The precision characteristics of
      these assays are comparable with those reported for microalbuminuria. The
      clinical utility of measuring a panel of these markers was demonstrated in urine
      samples from 16 control subjects and from 46 individuals with insulin-dependent
      diabetes mellitus (IDDM) with various albumin excretion rates (AERs). TGF-beta1
      and T3C were used as markers of cytokine expression and of the renal fibrogenic
      process, whereas RBP excretion served as a marker of tubular injury or
      dysfunction. Compared with controls, T3C excretion was significantly increased in
      18 normoalbuminuric and further increased in 13 microalbuminuric (AER 20 < or =
      200 microg/min) IDDM subjects. RBP excretion was increased in macroalbuminuric
      IDDM subjects (AER >200 microg/min, overt nephropathy). Significant correlations
      were also found between AER and RBP in all but macroalbuminuric individuals,
      whereas TGF-beta1 correlated with T3C excretion in controls and in
      normoalbuminuric diabetic subjects. Urinary RBP but not AER was an excellent
      predictor of diabetic nephropathy as defined by serum creatinine (P = 0.0001).
      This underscores the importance of an early tubulopathy in the subsequent
      development of glomerulopathy and overt nephropathy. The data suggest that
      longitudinal monitoring of a panel of urinary markers such as that used in the
      current study may better define their relevance in progressive glomerulosclerosis
      and may also provide greater insight into the mechanisms underlying such process.

PMID- 9590368
TI  - Biological variations and genetic reference values for apolipoprotein E serum
      concentrations: results from the STANISLAS cohort study.
AB  - Serum apolipoprotein (apo) E concentrations were determined by immunoturbidimetry
      in 4284 subjects from 4 to 71 years of age and belonging to 1003 nuclear families
      recruited for the STANISLAS cohort study between January 1994 and August 1995.
      Values for apo E ranged from 16 to 169 mg/L, with a geometric mean +/- SD values
      of 46.6 +/- 13.8 mg/L in the overall sample. The interindividual variability
      varied from 24.6% to 32.0% among family members. Females exhibited higher apo E
      values than males until the age of 17-26 years. Conversely, after the age of 26
      years, serum apo E concentrations were higher in men than in women. Biological
      factors affecting serum apo E concentrations were described in fathers, mothers,
      sons, and daughters and explained up to 32.0% of the apo E variability in
      daughters and 19.0% in fathers. The main biological factors affecting apo E
      concentrations were the following: apo E polymorphism, waist-to-hip ratio, oral
      contraceptive intake, puberty, body mass index, age, and gender. Given the
      importance of apo E polymorphism in the regulation of apo E concentrations, we
      recommend the use of genetic-based reference values for the clinical
      interpretation of serum apo E concentrations.

PMID- 9590369
TI  - Flow cytometry with a monoclonal antibody to the low density lipoprotein receptor
      compared with gene mutation detection in diagnosis of heterozygous familial
      hypercholesterolemia.
AB  - We used a fluorescence flow cytometry assay with a monoclonal low density
      lipoprotein (LDL) receptor-specific antibody to detect LDL receptor expression on
      blood T lymphocytes and monocytes. We prepared peripheral blood mononuclear cells
      from patients with genetically verified LDL receptor-defective (Trp66-Gly
      mutation, n = 17) or receptor-negative (Trp23-stop mutation, n = 17) heterozygous
      familial hypercholesterolemia (FH) and from healthy individuals (n = 24). The
      cells were stimulated to express the maximum amount of LDL receptor by
      preincubation in lipoprotein-deficient medium. A dual-labeling technique allowed
      flow cytometric analysis of LDL receptor expression on cells identified by
      fluorescently conjugated surface marker antibodies. Knowing the LDL receptor gene
      mutation of the FH patients allowed us to compare the diagnostic capability of
      this functional assay with the DNA diagnosis and to validate the assay with
      molecular genetics instead of clinical indices of heterozygous FH. T lymphocytes
      expressed more LDL receptors and gave better diagnostic results than monocytes,
      and cells from patients with either the Trp66-Gly or the Trp23-stop mutation had
      variable but significantly reduced LDL receptor expression. The data indicate
      that this fluorescence flow cytometry assay is unsuitable for diagnosis of
      individual cases of heterozygous FH but that it may be useful for functionally
      characterizing mutations in the LDL receptor gene.

PMID- 9590370
TI  - 4-Chlorotestosterone acetate metabolites in cattle after intramuscular and oral
      administrations.
AB  - The use of 4-chlorotestosterone acetate by farmers for cattle fattening was
      recently demonstrated although the use of this anabolic steroid is strictly
      forbidden in the European Union. We investigated the metabolism of 4
      chlorotestosterone acetate in the bovine species after intramuscular and oral
      administration. Nineteen metabolites were detected in urine after intramuscular
      injection, and eight metabolites were identified. For this purpose, preparative
      HPLC, mass spectrometry with different ionization modes (electronic impact and
      chemical ionization), and different acquisition techniques were used (high
      resolution, selected ion monitoring, and scan measurement). Metabolite
      stereoisomerism was determined on the basis of retention time and organic
      synthesis. 4-Chloroepitestosterone (M2), 4-chloroandrost-4-en-3alpha-ol-17-one
      (M3), and 4-chloroandrost-4-ene-3,17-dione (M4) were identified as the main
      urinary markers of intramuscular administration. On the other hand, 4
      chloroandrost-4-ene-3alpha,17beta-diol (M7), 4-chloroandrostan-3beta-ol-17-one
      (M5), and M2 were the primary indicators of an oral administration. In addition,
      we have shown that 95% of the metabolites were sulfo-conjugated, except for M3,
      which was partially conjugated to glucuronic acid. Finally, the main metabolites
      (M2, M3, and M4) were easily identified for 1.5 months after intramuscular
      administration.

PMID- 9590371
TI  - Indirect enzyme-linked immunosorbent assay for the quantitative estimation of
      lysergic acid diethylamide in urine.
AB  - A new antibody to lysergic acid diethylamide (LSD) was used to develop a novel
      indirect ELISA for the quantification of drug in urine. Evaluation of the new
      assay with the commercially available LSD ELISA (STC Diagnostics) shows improved
      performance. The test requires 50 microL of urine, which is used to measure
      concentrations of drug in the microg/L to ng/L range. The limit of detection was
      8 ng/L compared with 85 ng/L in the commercial assay, and analytical recoveries
      were 98-106%. Our test detected 0.1 microg/L of LSD in urine with an intraassay
      CV of 2.4% (n = 8) compared with 6.0% for a 0.5 microg/L sample in the commercial
      assay (n = 20). The upper and lower limits of quantification were estimated to be
      7 microg/L and 50 ng/L, respectively. Specificity was evaluated by measuring the
      extent of cross-reactivity with 24 related substances. Drug determination using
      the new assay offers both improved sensitivity and precision compared with
      existing methods, thus facilitating the preliminary quantitative estimation of
      LSD in urine at lower concentrations with a greater degree of certainty.

PMID- 9590372
TI  - Accurate measurement of cholecystokinin in plasma.
AB  - Shortage of reliable plasma assays has hampered studies of cholecystokinin (CCK).
      The assay problems are low plasma concentrations, extensive molecular
      heterogeneity, and close homology of CCK to gastrin, which circulates in higher
      concentrations. To develop an accurate CCK RIA, antibodies were raised in
      rabbits, guinea pigs, and mice in titers from 200 to 4000000. The specificity of
      the antisera was tested with homologous peptides, and tissue and plasma extracts.
      Rabbit 92128 produced antibodies in high titer (> or =500000) with sufficient
      avidity (K(o)eff > or = 10(12) mol(-1)) and the desired specificity. The
      antiserum binds the bioactive forms of CCK with equimolar potency and displays no
      reactivity with gastrin. CCK concentrations in plasma from healthy humans rose
      from 1.13 +/- 0.10 pmol/L (mean +/- SE, n = 26) to 4.92 +/- 0.34 pmol/L after a
      mixed meal. Chromatography of human plasma revealed traces of CCK-58, a
      predominance of CCK-33 and CCK-22, and moderate amounts of CCK-8. The results
      show that it is possible to produce specific CCK-antisera using a sulfated CCK-12
      analog.

PMID- 9590373
TI  - Misleading serum free thyroxine results during low molecular weight heparin
      treatment.
AB  - Measured free thyroxine concentrations in serum increase markedly after
      intravenous heparin administration, but the effect of heparin administered
      subcutaneously has not been adequately documented. We found in vitro increases of
      up to 63% in measured FT4 after a single dose of subcutaneous heparin
      (enoxaparin, 2000 units) in nine healthy volunteers, and the magnitude of these
      increases was correlated with initial serum triglyceride concentrations (r =
      0.93, P <0.005) and in vitro free fatty acid release (r = 0.88, P <0.005). In 10
      cardiac inpatients receiving repeated doses of enoxaparin (2000 units twice
      daily), measured FT4 increased by up to 171% in specimens taken 2-6 h after
      injection. When specimens were obtained 10 h after injection, the effect appeared
      to be minimized, with in vitro increases of <40%, but such increases may still be
      sufficient to cause interpretative errors. If FT4 estimation is absolutely
      necessary in patients receiving enoxaparin, specimens should be taken > or =10 h
      postdose and analyzed within 24 h.

PMID- 9590375
TI  - Optimizing frequency and number of controls for automatic multichannel analyzers.
AB  - Sampling strategy fundamentally influences the effectiveness of quality control
      with control charts. This study shows a simple approach for optimizing the
      control strategy for automatic multichannel analyzers that takes into account
      cost-efficiency considerations. Our main focus is on the frequency of controls
      necessary. The methods used are based on a field study (on a Hitachi/BM 747), the
      views of experts, and computer simulations of customary cost-models together with
      a survey of the literature. We found that industrial cost-models are applicable
      only with distinct limitations, but-unlike the test-yield model-they offer
      consistent solutions. On the basis of the field study and the opinions of
      experts, we adjusted the control strategy to account for inadequacies in the
      theoretical models. The combined result is that, for effective operation, the
      number of samples between controls may reach values up to 100 and should not
      require controls more often than every 30 samples on comparable multichannel
      analyzers. For adequate statistical performance, a simple 3-SD Shewhart chart
      usually requires not more than two controls of the same material at each time.

PMID- 9590374
TI  - Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic
      peptide in human plasma.
AB  - Recently, the N-terminal fragment of proatrial natriuretic peptide (N-terminal
      proANP) has been proposed as a marker of chronic congestive heart failure. In
      this study, we established a two-step immunoradiometric assay using monoclonal
      antibodies and synthetic N-terminal proANP (1-67) as a standard. It allows us to
      measure plasma N-terminal proANP in only 4 h without prior extraction. The
      detection limit of this assay was 15 pmol/L for a 100 microL sample of plasma.
      Within-run CVs ranged from 1.7% to 2.9% and between-run CVs ranged from 4.2% to
      5.1%. The dilution curves of plasma samples showed good linearity and analytical
      recovery was 89-104%. The mean (+/-SD) N-terminal proANP in plasma of 33 healthy
      subjects was 188 (+/-71) pmol/L and 1030 (+/-411) pmol/L in 25 patients with
      heart failure. Our immunoradiometric assay is rapid and precise enough for
      routine determination of N-terminal proANP in human plasma.

PMID- 9590376
TI  - Performance of Deming regression analysis in case of misspecified analytical
      error ratio in method comparison studies.
AB  - Application of Deming regression analysis to interpret method comparison data
      presupposes specification of the squared analytical error ratio (lambda), but in
      cases involving only single measurements by each method, this ratio may be
      unknown and is often assigned a default value of one. On the basis of
      simulations, this practice was evaluated in situations with real error ratios
      deviating from one. Comparisons of two electrolyte methods and two glucose
      methods were simulated. In the first case, misspecification of lambda produced a
      bias that amounted to two-thirds of the maximum bias of the ordinary least
      squares regression method. Standard errors and the results of hypothesis-testing
      also became misleading. In the second situation, a misspecified error ratio
      resulted only in a negligible bias. Thus, given a short range of values in
      relation to the measurement errors, it is important that lambda is correctly
      estimated either from duplicate sets of measurements or, in the case of single
      measurement sets, specified from quality-control data. However, even with a
      misspecified error ratio, Deming regression analysis is likely to perform better
      than least-squares regression analysis.

PMID- 9590377
TI  - Evaluation of growth hormone assays using ratio plots.
AB  - To permit comparison between growth hormone (GH) results obtained using the
      Pharmacia polyclonal assay and the Delfia monoclonal assay, we used both methods
      to measure GH concentrations in peak GH responses to the pyridostigmine-growth
      hormone-releasing-hormone (PD-GHRH) test and in unstimulated samples from 40
      healthy adults and 31 patients with suspected GH deficiency. Ratio plots were
      used for the comparison, and acceptability criteria were based on inherent
      analytical imprecision and on analytical quality specifications. The mean ratio
      (r; Pharmacia/Delfia) for the peak GH responses in 40 healthy adults was
      calculated to be 1.59, and the 95% prediction interval for ratios fulfilling the
      imprecision criterion was applied. For GH values >1 mIU/L, the peak and
      unstimulated GH ratios in healthy adults and patients were within the 95%
      prediction interval, and fulfilled the biological criterion as well. Therefore,
      the conversion factor of 1.59 is applicable for the evaluation of GH-stimulation
      tests.

PMID- 9590378
TI  - False-positive immunochemical screen for methadone attributable to metabolites of
      verapamil.

PMID- 9590379
TI  - Simple, rapid nonradioactive method to detect the three most prevalent hereditary
      fructose intolerance mutations.

PMID- 9590380
TI  - Increased serum lipase with associated normoamylasemia in cancer patients.

PMID- 9590381
TI  - An improved method for the detection of the thermolabile variant of
      methylenetetrahydrofolate reductase.

PMID- 9590382
TI  - A simple electrophoretic method for phenotyping apo(a): phenotype frequency in
      healthy subjects from Paris, France.

PMID- 9590383
TI  - Evaluation of homogeneous high-density lipoprotein cholesterol assay on a
      BM/Hitachi 747-200 analyzer.

PMID- 9590384
TI  - Effects of anticoagulants in amino acid analysis: comparisons of heparin, EDTA,
      and sodium citrate in vacutainer tubes for plasma preparation.

PMID- 9590385
TI  - Plasma S-100b protein concentration in healthy adults is age- and sex
      independent.

PMID- 9590386
TI  - S100 blood concentrations in children subjected to cardiopulmonary by-pass.

PMID- 9590387
TI  - Kind of sample as preanalytical determinant of matrix metalloproteinase 2 and 9
      and tissue inhibitor of metalloproteinase 2 in blood.

PMID- 9590388
TI  - Adequacy of NCEP recommendations for total cholesterol, triglycerides, HDLC, and
      LDLC measurements.

PMID- 9590389
TI  - Modern quality management misunderstood?

PMID- 9590390
TI  - Standardization of hemoglobin A1c.

PMID- 9590391
TI  - Evaluation of carbohydrate-deficient transferrin.

PMID- 9590392
TI  - Standards of laboratory practice: antidepressant drug monitoring. National
      Academy of Clinical Biochemistry.
AB  - Therapeutic drug monitoring (TDM) for certain tricyclic antidepressants (TCAs)
      and lithium is supported on the basis of clearly defined therapeutic ranges. TDM
      is of particular importance in individuals whose pharmacokinetic behavior may
      differ from that of the general population or is changing as the result of aging
      and maturation. Once steady-state drug concentrations are achieved, serum or
      plasma specimens should be collected during the terminal drug-elimination phase
      and separated from cellular blood components immediately. Methods of analysis
      must be specific for parent drug and active metabolites and demonstrate
      imprecision (CVs) within 5-10% over the therapeutic range. For support of
      overdose situations, semiquantitative values for TCAs and quantitative measures
      of lithium should be available within 1 h, and routine TDM results should be
      reported within 24 h of receipt in the laboratory. Standardized and rigorous
      laboratory practices contribute to improved therapeutic management.

PMID- 9590393
TI  - Standards of laboratory practice: antiepileptic drug monitoring. National Academy
      of Clinical Biochemistry.
AB  - Discussion and development of standards for appropriate monitoring led to the
      following key recommendations for ordering, sampling, and analyzing antiepileptic
      drugs: Monitoring should usually be done on trough specimens after steady-state
      has been reached and always with an appropriate medical indication; non-steady
      state concentrations may be indicated in selected situations. Monitoring of free
      phenytoin and free valproic acid is indicated in specific situations and should
      be done in serum. The metabolite of primidone, phenobarbital, should be measured
      concurrently with parent drug, but the active metabolite of carbamazepine does
      not need to be monitored unless the patient is exhibiting an unusual toxic
      response that cannot be otherwise explained. Assays used for antiepileptic drug
      monitoring should display a long-term CV of <10% and preferably <5%.
      Subtherapeutic and supratherapeutic drug concentrations should be investigated on
      a regular basis as part of a quality assurance process.

PMID- 9590395
TI  - Standards of laboratory practice: analgesic drug monitoring. National Academy of
      Clinical Biochemistry.
AB  - Analgesics are the most commonly consumed over-the-counter preparations in the
      United States. They are used in the treatment of various pain syndromes and other
      medical conditions. Although analgesics are generally perceived to be safe
      agents, serious toxicity may occur in the setting of acute overdose, chronic
      abuse, or overuse. The indications for therapeutic drug monitoring in patients
      using these medications appropriately is as yet not well defined. The emphasis of
      this discussion, therefore, is on recommendations for monitoring in situations
      where toxicity is suspected. Preanalytical, analytical, and practice issues
      including drug interactions, frequency of monitoring, pertinent ancillary tests,
      reporting, and special patient groups at risk for toxicity are reviewed. Recent
      information from a major manufacturer of evacuated tubes arguing against the use
      of gel tubes for blood collection for drug monitoring is included.
      Colorimetric/enzymatic/immunoassays for the routine/stat monitoring of
      acetaminophen and salicylate and diflunisal cross-reactivity with most of the
      currently used salicylate assays are presented. Achiral and chiral
      chromatographic assays and newly introduced columns such as restricted access
      media and/or automated chromatographic systems are reviewed for the analysis of
      ibuprofen, naproxen, and the recently introduced tramadol. Finally, concepts
      regarding future directions including drug chirality and chiral analysis are
      presented.

PMID- 9590394
TI  - Standards of laboratory practice: cardiac drug monitoring. National Academy of
      Clinical Biochemistry.
AB  - In this Standard of Laboratory Practice we recommend guidelines for therapeutic
      monitoring of cardiac drugs. Cardiac drugs are primarily used for treatment of
      angina, arrhythmias, and congestive heart failure. Digoxin, used in congestive
      heart failure, is widely prescribed and therapeutically monitored. Monitoring and
      use of antiarrhythmics such as disopyramide and lidocaine have been steadily
      declining. Immunoassay techniques are currently the most popular methods for
      measuring cardiac drugs. Several reasons make measurement of cardiac drugs in
      serum important: their narrow therapeutic index, similarity in clinical
      complications and presentation of under- and overmedicated patients, need for
      dosage adjustments, and confirmation of patient compliance. Monitoring may also
      be necessary in other circumstances, such as assessment of acetylator phenotypes.
      We present recommendations for measuring digoxin, quinidine, procainamide (and N
      acetylprocainamide), lidocaine, and flecainide. We discuss guidelines for
      measuring unbound digoxin in the presence of an antidote (Fab fragments), for
      characterizing the impact of digoxin-like immunoreactive factor (DLIF) and other
      cross-reactants on immunoassays, and for moni-toring the unbound (free fraction)
      of drugs that bind to alpha1-acid glycoprotein. We also discuss logistic,
      clinical, hospital, and laboratory practice guidelines needed for implementation
      of a successful therapeutic drug monitoring service for cardiac drugs.

PMID- 9590396
TI  - Standards of laboratory practice: theophylline and caffeine monitoring. National
      Academy of Clinical Biochemistry.
AB  - Theophylline is used in the treatment of asthma and chronic obstructive pulmonary
      disease. The use of theophylline has declined with the advent of potent steroid
      inhalants. Because of the therapeutic index of this drug, monitoring of
      theophylline concentrations in plasma is essential. Monitoring should be done on
      trough specimens after steady-state has been reached. Non-steady-state
      concentrations may be indicated in selected situations. Caffeine is used to treat
      apnea of the newborn because of its low toxicity. Monitoring is often by clinical
      effect. Monitoring of serum concentrations should be performed in cases where
      there is no clinical response or if there is suspected toxicity.

PMID- 9590397
TI  - Laboratory guidelines for monitoring of antimicrobial drugs. National Academy of
      Clinical Biochemistry.
AB  - Few antimicrobial drugs meet the requirements for therapeutic drug monitoring.
      Those that are monitored include the aminoglycosides (gentamicin, tobramycin, and
      amikacin), chloramphenicol, and in some cases, vancomycin. For these drugs, there
      is evidence of a relationship between serum concentration, efficacy, and/or the
      incidence of adverse or toxic events. Monitoring begins with the appropriate
      timing of collection and continues through the analytical process to the
      integration of all data used to guide the clinician's next decision.

PMID- 9590399
TI  - Bile salt hydrophobicity modulates subselection of biliary lecithin species in
      rats depleted of bile salt pool.
AB  - Although bile salts play an important role in the secretion of biliary lipid,
      little is known about the relationship between bile salt hydrophobicity and the
      selection of lecithin species to be secreted into bile. We therefore investigated
      whether bile salts modulate the selection of biliary lecithin subspecies. Rats
      that were depleted of the bile salt pool were infused with taurocholate (50, 100,
      200, and 400 nmol/min/100 g body weight), taurochenodeoxycholate (25, 50, 100,
      and 200 nmol/min/100 g body weight), tauroursodeoxycholate (100, 200, 400, and
      800 nmol/min/100 g body weight), or taurobetamuricholate (100, 200, 400, and 800
      nmol/min/100 g body weight). Bile was collected to analyze bile flow, bile acid
      output, cholesterol levels, and lecithin levels. The hydrophobic-hydrophilic
      balance of the bile salts and biliary lecithin species was assessed by
      determining the retention times during reverse-phase high-performance liquid
      chromatography. Biliary lecithin secretion rates correlated with the
      hydrophobicity index of the biliary bile salts administered. Thus, biliary
      lecithin hydrophobicity increased with increasing bile salt hydrophobicity,
      whereas the molar cholesterol-lecithin ratio in the bile decreased. In
      conclusion, bile salt hydrophobicity regulates the selection of biliary lecithin
      subspecies during biliary secretion and thereby modulates, at least in part, bile
      cholesterol metastability. Thus, bile salt hydrophobicity accounts for the
      physicochemical conditions determining bile lipid metastability.

PMID- 9590398
TI  - Dissolution of gallbladder stones with methyl tert-butyl ether and stone
      recurrence: a European survey.
AB  - Since there are now several ways to treat symptomatic gallstone disease, one is
      able to select treatment on the basis of the patient's comfort, the
      practicability, effectiveness, and side effects of the technique, and the
      relative costs. In order to assess the present status of contact dissolution with
      methyl tert-butyl ether with regard to these aspects, the present enquiry reports
      the data of 21 European hospitals. Eight hundred three patients were selected for
      contact litholysis of cholesterol gallbladder stones using methyl tert-butyl
      ether. Percutaneous transhepatic puncture of the gallbladder was performed under
      x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times
      of 268 patients from one single center were compared to those of 535 patients
      from the other 20 centers. Two hundred sixty-four patients were followed for five
      years to assess stone recurrence. Physicians were asked how they assessed the
      expenditure of the method, the discomfort to the patients, and the staffing
      situation. Patients were asked to indicate their acceptance on an analog scale.
      Puncture was successful in 761 (94.8%) patients. Prophylactic administration of
      antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In
      315 (43.5%) sludge remained in the gallbladder. The most severe complication was
      bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy.
      Toxic injuries due to the ether were not reported. Method-related lethality
      amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in
      solitary stones and about 70% in multiple stones over five years. Patients with
      multiple stones developed recurrent stones almost twice as often as those with
      solitary stones. The probability of stone recurrence in patients with sludge in
      the gallbladder after catheter removal was not statistically significantly
      different from those without sludge. Seventy to 90% of the centers found the
      puncture to be simple and not distressing for patients and the relation between
      expenditure and therapeutic success to be acceptable. The acceptance of contact
      litholysis by the patients was excellent. Contact litholysis when applied by an
      experienced team provides real advantages in the treatment of gallstone disease.
      The method is technically simple, well accepted by the patients, and can be
      easily applied in community hospitals. Contact litholysis may be of particular
      value in patients who are not suitable for anesthesia or surgery.

PMID- 9590400
TI  - Intragastric alcohol causes endothelin release from feline pancreas.
AB  - The mechanism by which alcohol causes pancreatic damage is still largely unknown.
      One important contributory factor may be the endothelins, potent vasoconstricting
      endothelial-derived peptides. The aim of this study was to examine in vivo
      endothelin release from the pancreatic vascular endothelium after alcohol
      ingestion. In anesthetized cats immunoreactive endothelin was measured in serum
      after instillation of alcohol into the stomach (20 ml, 40%). After intragastric
      alcohol, a rise in endothelin was seen in pancreatic venous effluent (to a mean
      of 24.5 +/- 7.7 pg/ml at 60 min). Control serum from the femoral artery exhibited
      no rise in endothelin (2.11 +/- 1.2 pg/ml). Pancreatic blood flow was
      significantly decreased in a further group to 93% basal after intravenous
      infusion of 0.1 nmol/kg ET-1 and to 61% after infusion of 1 nmol/kg ET-1. Portal
      serum levels of endothelin were 105 pg/ml and 15 pg/ml, respectively, immediately
      following bolus infusion and decreased to normal levels within 120 sec. We
      conclude that the serum endothelin rise after intragastric ethanol may be a major
      factor behind the drop in pancreatic blood flow.

PMID- 9590401
TI  - Histological findings of gallbladder mucosa in 95 control subjects and 80
      patients with asymptomatic gallstones.
AB  - The histological appearance of gallbladder mucosa in 95 control subjects and in
      80 patients with asymptomatic gallstones separated according to age and sex was
      determined in a prospective study. The number and size of stones in the latter
      group were also analyzed. Among controls, 33% showed abnormal histological
      findings, mainly chronic cholecystitis, which increased with age and was
      frequently seen among women. All patients with asymptomatic gallstones showed
      chronic cholecystitis and/or cholesterolosis, and 5% showed acute inflammatory
      changes. In 55% of them a single stone was found. These findings suggest that
      chronic inflammatory changes can occur in the gallbladder mucosa prior to the
      appearance of macroscopic stones at the gallbladder.

PMID- 9590402
TI  - Risk factors for gallstone disease in Mexicans are similar to those found in
      Mexican-Americans.
AB  - According to epidemiological studies, gallstone disease is a very common disease
      in Mexican-Americans and Mexicans. However, the major risk factors for
      cholelithiasis in Mexicans have not been identified. We designed a case-control
      study in a group of Mexican subjects with and without gallstone disease confirmed
      by ultrasound. These subjects were prospectively studied over a three-year
      period. Clinical and epidemiological data were collected by means of a
      questionnaire. A total of 1500 subjects were included in this study: 1000 with
      and 500 without gallstone disease. The major risk factor in both men and women
      was body mass index [odds ratio (OR) 1.64 and 1.96, respectively; P < 0.008 and
      0.001]. In addition, parity was an important factor in women (OR 2.17, P <
      0.001), whereas age was associated with gallstone disease in men (OR 1.43, P <
      0.001). We found that body mass index, parity, and age were the principal risk
      factors for gallstone disease in this group of Mexican subjects. These results
      are similar to those found in Mexican-American populations.

PMID- 9590403
TI  - Xanthogranulomatous cholecystitis.
AB  - Xanthogranulomatous cholecystitis exists in a small but significant proportion of
      routine cholecystectomy specimens. A few recent reports have shown a possible
      association of this disease with carcinoma of the gallbladder. All
      cholecystectomized specimens were prospectively evaluated over a period of two
      and half years in a single surgical unit to examine the incidence of
      xanthogranulomatous cholecystitis and its association, if any, with carcinoma of
      the gallbladder in an area that is prone to gallbladder diseases. A total of 460
      cholecystectomies were performed for various gallbladder diseases. Histological
      confirmation revealed chronic cholecystitis in 311 (67.6%) cases, carcinoma of
      the gallbladder in 62 (13.5%), acute cholecystitis in 29 (6.3%),
      xanthogranulomatous cholecystitis in 41 (8.9%), and xanthogranuloma and carcinoma
      of the gallbladder in one case (0.2%) only. Almost all cases were suspected to
      have chronic cholecystitis on clinical and ultrasonographic features. Two
      specimens on gross examination showed mass lesions, and hence were suspected to
      be carcinoma of the gallbladder. Subsequent frozen section and histopathology
      demonstrated xanthogranulomatous cholecystitis. Only one case of xanthogranuloma
      was found to be associated with carcinoma of the gallbladder but no firm
      association could be established between xanthogranulomatous cholecystitis and
      carcinoma of the gallbladder.

PMID- 9590404
TI  - Hyperlipidemic pancreatitis in a primigravida adolescent.

PMID- 9590406
TI  - Dynamics of the level of randomness in gastric electrical activity.
AB  - This study was undertaken to investigate the dynamics of the level of randomness
      in gastric electrical signals. Combined recordings of internal gastric electrical
      activity (GEA) and electrogastrograms (EGG) were obtained from 16 unconscious
      dogs and two postoperative patients. The signals were amplified using specially
      designed amplifiers with flexible frequency range and were digitized with 10-Hz
      sampling frequency. The 4.27-min portions of the digital signals were subjected
      to a previously described turning point test for randomness. The distributions of
      the number of turning points (NTP) in successive time intervals calculated from
      all GEA signals were compared to the estimated NTP distribution of a random
      signal. NTP dynamics of internal GEA signals was also correlated to the NTP
      dynamics of cutaneous EGG. In five of 16 recordings from the dogs and in two of
      the 14 recordings from the patients, NTP values calculated from some internal GEA
      channels exceeded the 1% probability level for entering the normal NTP
      distribution of a random signal (P > 0.01). In all measurements the distributions
      of the NTP values recorded from cutaneous EGG channels were significantly
      different (P < 0.01) from the NTP distribution of a random signal. There was
      significant correlation (P < 0.01) between the NTP dynamics of internal GEA and
      EGG. The level of randomness in internal GEA recorded with the short-distance
      bipolar technique is substantially higher than that in cutaneous EGG, probably
      due to the occurrence of spike activity. Although the level of randomness in EGG
      is affected by many external factors, its dynamics correlated significantly with
      the level of randomness in internal GEA.

PMID- 9590405
TI  - Distal small bowel hormones: correlation with fasting antroduodenal motility and
      gastric emptying.
AB  - The aim of the present study was to study the interdigestive motor complex (MMC),
      distal small intestinal hormones, and gastric emptying in normal-weight and obese
      subjects before and after jejunoileal bypass (JIB). Therefore, fasting
      antroduodenal motility, gastric emptying, and RIA for motilin (MOT), neurotensin
      (NT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) was performed in nine
      obese subjects before (BMI 42 +/- 4 kg/m2) and nine months after (BMI 31 +/- 4)
      JIB, and in two groups of nine age- and sex-matched controls (BMI 23 +/- 1 and 21
      +/- 1). The rate of gastric emptying was faster in obese subjects and GLP-1 lower
      compared to normal-weight controls. After JIB, fewer phase III of the MMC were
      observed; fasting levels of PYY were elevated during the MMC; postprandial levels
      of NT, PYY, and GLP-1 were elevated; and gastric emptying was delayed. Our
      results suggest that there may be an association between an impaired GLP-1
      response after food intake and obesity, and after JIB, PYY seems to regulate
      interdigestive motility while GLP-1 may regulate early gastric emptying.

PMID- 9590407
TI  - Characterization of propagating contractions in proximal colon of ambulatory mini
      pigs.
AB  - The aim of this study was to characterize propagating contractions in the
      unprepared colon of freely ambulating mini pigs. A telemetric method was used to
      record colonic motility continuously for six consecutive days in a 40-cm segment
      of proximal colon. Propagating contractions occurred over a wide range of
      propagation rates (0.4-16.7 cm/sec), peak amplitudes (10-116 mm Hg) and pressure
      wave durations (5.3-40.0 sec). Propagating contractions were divided into two
      groups by duration and wave-form: short-duration symmetrical and long-duration
      asymmetrical. Short-duration (7.8 +/- 0.9 sec) symmetrical wave-from propagating
      contractions exhibited a higher frequency (27.9 +/- 2.6 events/day), more rapid
      propagation rate (3-16.7 cm/sec; mean +/- SEM: 4.9 +/- 1.7 cm/sec), and a lower
      peak amplitude (31.2 +/- 0.9 mm Hg) compared to long-duration (19.2 +/- 5.1 sec)
      asymmetrical propagating contractions, which were less frequent (6.1 +/- 0.7
      events/day), slower in propagation rate (0.4-2 cm/sec; mean +/- SEM: 1.5 +/- 0.7
      cm/sec), and higher in peak amplitude (51.6 +/- 2.4 mm Hg). The results show that
      propagating contractions occur over a wide spectrum, from short-duration, low
      amplitude, rapidly propagating contractions to long-duration, high-amplitude,
      slowly propagating contractions.

PMID- 9590408
TI  - Expression of p53 and p21 are independent prognostic factors in patients with
      serosal invasion by gastric carcinoma.
AB  - To evaluate whether the expression of p53 and that of p21 are independent
      prognostic factors in patients with advanced gastric cancer, we investigated
      clinicopathological factors and the expression of p53 and p21 in 158 patients
      with gastric cancer that had invaded the serosa and who had undergone curative
      gastrectomy. In multivariate survival analysis of 156 surviving patients, we
      evaluated the size of the tumor, lymph node metastasis, venous invasion, lymph
      node dissection, expression of p53, and expression of p21 as independent
      prognostic factors. Moreover, we divided patients into four groups according to
      the expression of p53 and p21 in their tumors [group A, p53-/p21-, N = 40 (one
      died within 30 days of surgery); group B, p53-/p21+, N = 23; group C, p53+/p21-,
      N = 58; and group D, p53+/p21+, N = 37 (one died within 30 days of surgery)]. The
      5- and 10-year survival rates of 39 patients in group A were 71.7% and 64.3%,
      those of 23 patients in group B were 81.4% and 81.4%, those of 58 patients in
      group C were 35.6% and 30.2%, and those of 36 patients in group D were 67.9% and
      60.7%. The prognosis of patients in group C was poorer than that of patients in
      the other three groups. This result indicates that the evaluation of the
      expression of both p53 and p21 expression might provide prognostic information
      that is more accurate than that provided by evaluation of the expression of p53
      alone.

PMID- 9590409
TI  - Gastric adenocarcinoma producing neuron-specific enolase.

PMID- 9590410
TI  - Malignant rhabdoid tumor of the small intestine in an adult: a case report with
      immunohistochemical and ultrastructural findings.

PMID- 9590411
TI  - REP-PCR fragments as biomarkers for differentiating gastroduodenal disease
      specific Helicobacter pylori strains.
AB  - We previously identified four potential putative gastroduodenal disease fragments
      by using the interspersed repetitive extragenic palindromic DNA sequence based
      PCR (REP-PCR) technique. We investigated these fragments with regard to their
      disease specificity. The putative disease-specific REP-PCR fragments were cloned,
      mapped by restriction enzymes, cross-hybridized, and confirmed by Southern
      hybridization. The four fragments were also used as probes against REP-PCR
      amplicons from H. pylori isolates obtained from gastritis (N = 20), duodenal
      ulcer (N = 30), and gastric cancer patients (N = 30). Three of these fragments
      (1.4- and 0.76-kb for gastritis; 1.35 kb for duodenal ulcer) were amplified
      without any discrimination between any disease-specific H. pylori isolates.
      However, amplification following hybridization with the fourth 0.81-kb fragment
      was observed only from gastritis (60%) and duodenal ulcer (52%) but with none
      (0%) of gastric cancer patients. Nucleotide sequence analysis of the 0.81-kb
      fragment revealed that it was an open reading frame of the hypothetical protein
      HP0373 matched to the position of 380,966 to 383,068 nucleotides of the H. pylori
      complete genome sequence. Hence, the REP-PCR sequence was not a extragenic
      palindromic DNA sequence. The hypothetical protein was also present in all the
      tested isolates. The REP-PCR fingerprinting technique is useful to differentiate
      disease-specific H. pylori strains based on the interspersed repetitive
      extragenic palindromic DNA sequences; however, it may not be useful to identify
      disease-specific virulence determinant(s) without being confirmed by DNA sequence
      analysis and functional studies.

PMID- 9590412
TI  - Prevalence of upper gastrointestinal lesions and Helicobacter pylori infection in
      Crohn's disease.
AB  - Crohn's disease can affect the upper gut with reported variable frequency,
      although concurrent Helicobacter pylori infection has been reported to be low. We
      prospectively investigated the prevalence of esophageal, gastric, and duodenal
      lesions and Helicobacter pylori infection in 67 Crohn's disease, 41 ulcerative
      colitis patients, and 43 controls. Symptoms, esophagogastroduodenoscopy, and
      multiple biopsies were performed on all patients consecutively. Endoscopic
      lesions were found in 63% of Crohn's disease patients, with a Helicobacter pylori
      prevalence of 28%. Granulomas were found in three patients. Twenty-two percent of
      the ulcerative colitis patients had lesions, with a 29% prevalence of
      Helicobacter pylori infection. Half of the controls had pathological endoscopy,
      and Helicobacter pylori was positive in 40% of the cases. Subjective symptoms did
      not predict the presence of endoscopic lesions or Helicobacter pylori infection
      in inflammatory bowel disease patients. Chronic gastritis and duodenitis are
      common in Crohn's disease patients, and the majority are not associated with
      Helicobacter pylori infection.

PMID- 9590413
TI  - Rabeprazole in treatment of acid peptic diseases: results of three placebo
      controlled dose-response clinical trials in duodenal ulcer, gastric ulcer, and
      gastroesophageal reflux disease (GERD). The Rabeprazole Study Group.
AB  - Rabeprazole, a new proton pump inhibitor, was studied in patients with acid
      peptic-related diseases (duodenal ulcer, gastric ulcer, GERD) in three placebo
      controlled, double-blind, randomized clinical trials. Men and women over the age
      of 18 were enrolled if the presence of an active duodenal or gastric ulcer or
      erosive or ulcerative esophagitis was confirmed on upper gastrointestinal
      endoscopy. Patients were randomly allocated to either placebo or rabeprazole 20
      mg or 40 mg in the duodenal and gastric ulcer protocols or to placebo or
      rabeprazole 10 mg, 20 mg, or 40 mg in the GERD protocol. All doses of rabeprazole
      in all three studies were statistically significantly superior to placebo in
      healing acid-related lesions. There were no treatment differences between the
      rabeprazole doses in healing active peptic lesions. The incidence of positive
      [13C]urea breath test for H. pylori was 53% in patients with duodenal or gastric
      ulcers. H. pylori status was not effected by treatment with rabeprazole.

PMID- 9590415
TI  - Comparative study of potential for bisphosphonates to damage gastric mucosa of
      rats.
AB  - Bisphosphonates have generally few clinical adverse effects, the most common
      being gastrointestinal disturbances. It is generally believed that
      bisphosphonates with a primary amine are more irritating to the gastrointestinal
      tract than those without a primary amine. The objective of this study was to
      compare the gastric irritation potential of an amino bisphosphonate (alendronate)
      to that of two nonamino bisphosphonates (risedronate and etidronate) in a rat
      model at pharmacologically equivalent and clinically relevant doses. The doses
      used were 1, 5, 10, and 30 mg/kg/day for alendronate and risedronate and 40, 200,
      400, and 1200 mg/kg/day for etidronate. These doses represent 5-150 times the
      recommended clinical dose. The drugs were given orally, daily by gavage for four
      weeks. The gastric irritation potential was assessed by gross and microscopic
      evaluation of multiple sections of the stomach. This study showed that, at
      pharmacologically equivalent doses, the gastric irritation potential for
      alendronate is no greater than that for etidronate or risedronate.

PMID- 9590414
TI  - Empirical therapy versus diagnostic tests in gastroesophageal reflux disease: a
      medical decision analysis.
AB  - Our objective was to describe the conditions that determine the costs of
      empirical therapy in gastroesophageal reflux disease (GERD). Our design was a
      threshold analysis using a decision tree. The costs of medications were estimated
      from the average wholesale prices. The costs of diagnostic procedures were
      expressed as the sum of physician and facility costs. A decision tree was modeled
      to calculate the threshold probability of GERD, for which empirical therapy
      became the preferred management strategy. Bayes' formula was used to transform
      the sensitivity and specificity of various symptoms and the joint occurrence of
      multiple symptoms into disease probabilities. The decision in favor of empirical
      therapy is influenced by four factors: the probability of GERD, the duration or
      costs of GERD therapy, the costs of erroneous empirical therapy in patients with
      diagnosis other than GERD, and the costs of diagnostic procedures. In general,
      the expected benefit of saving the costs of a diagnostic procedure outweighs the
      costs of occasional erroneous empirical therapy. However, if surgical therapy is
      considered or antisecretory therapy is administered for a time period of 10 or
      more years, diagnostic confirmation of GERD should be sought. In the long run,
      the failure to differentiate between peptic ulcer and GERD results in the highest
      cost associated with erroneous empirical therapy. In patients with multiple
      characteristic symptoms of GERD, the diagnosis can be ascertained with sufficient
      confidence to warrant empirical therapy.

PMID- 9590416
TI  - Dyspepsia and health care seeking in a community: How important are psychological
      factors?
AB  - The factors that drive subjects with dyspepsia in the community to seek medical
      care are uncertain. We aimed to identify whether psychological factors explain
      health care utilization among subjects with dyspepsia. A sample of residents of
      western Sydney selected randomly from the electoral rolls was mailed a validated
      self-report questionnaire. Dyspepsia was defined as pain or discomfort centered
      in the upper abdomen. Potential predictors of physician visits tested included
      gastrointestinal symptoms, neuroticism (by the Eysenck Personality
      Questionnaire), psychological morbidity (General Health Questionnaire), and
      sexual, physical, and emotional abuse (based on standardized criteria). Among 730
      subjects, 13% (95% CI 10.3-15.2%) had dyspepsia and 70% (95% CI 59.8-79.5%) had
      sought medical care. Subjects with dyspepsia had significantly higher neuroticism
      and psychological morbidity scores and reported childhood emotional abuse more
      often than those without dyspepsia (all P < 0.05), but none of these were
      independent predictors. Male gender (OR = 0.58, 95% CI 0.37-0.91), greater pain
      severity (OR = 2.49, 95% CI 2.12-2.91, P < 0.01), and meeting the Rome criteria
      for irritable bowel (OR = 2.0, 95% CI 1.06-3.78) were associated with dyspepsia
      subjects seeing a physician or alternative therapist for abdominal pain or
      discomfort, explaining 32% of the deviance. Pain severity (OR = 1.39, 95% CI 1.22
      1.58) and symptoms of five or more years duration (OR = 5.73, 95% CI 3.71-8.87)
      were predictive of dyspepsia subjects ever seeking care for abdominal pain or
      discomfort, explaining 15% of the deviance. Psychological factors were not
      significant predictors of seeking medical attention in dyspepsia. Health care
      seeking among community subjects with dyspepsia is explained in part by symptom
      severity and duration but not by neuroticism, psychological morbidity, or a
      history of abuse.

PMID- 9590417
TI  - Efficiency and efficacy of the electrogastrogram.
AB  - The efficiency and efficacy of the electrogastrogram (EGG) involve a few
      practical factors, including recording length, sample size, and the
      characteristics of subjects. The aim of this study was to investigate the effect
      of these factors on the accuracy of EGG analysis. Gastric myoelectrical activity
      was recorded using electrogastrography in 24 subjects (ages 22-91 years) for 1 hr
      in the fasting state and 2 hr after a test meal. Computerized spectral analysis
      was performed to compute EGG parameters, including dominant frequency, dominant
      power, and the percentage of 2-4 cycles per minute (cpm) slow waves. A parameter
      called misinterpretation was defined to investigate the effect of recording
      length. The results were as follows: (1) Using the recording length of 1 hr in
      each state as a gold standard, the misinterpretation for the recording length of
      30 min was 27% for the dominant frequency and 17% for the dominant power. When
      the recording length was reduced to 15 min, the misinterpretation increased to
      61% for the dominant frequency and 38% for the dominant power. (2) With a sample
      size of 10 subjects and a recording length of 60 min, a statistically significant
      postprandial increase was observed in the dominant frequency and power, and a
      trend in the postprandial increase of the regularity of the EGG was noted. When
      the sample size increased to 24 subjects, a significant postprandial increase was
      found in all these parameters. (3) None of the EGG parameters exhibited any
      significant difference between the younger and older subjects or between men and
      women. In conclusion, a recording length of 30-60 min seems to be appropriate and
      produces reliable and predictable results. Age and gender do not affect any of
      the EGG parameters.

PMID- 9590418
TI  - Antral endocrine cells in nonobese diabetic mice.
AB  - The antral endocrine cells were investigated in nonobese diabetic (NOD) mice by
      means of immunohistochemistry, image analysis, and radioimmunoassays (RIA). As
      controls BALB/CJ mice of the same age and sex as the NOD mice were used. The
      number of gastrin- and somatostatin-immunoreactive cells was significantly
      decreased in both prediabetic and diabetic mice. There was no statistical
      difference between the NOD mice and controls regarding the serotonin
      immunoreactive cells. Somatostatin levels as revealed by RIA in the antrum of
      both prediabetic and diabetic NOD mice were lower than those of the controls.
      There was no statistical difference in the level of antral gastrin between NOD
      mice and the controls. It was concluded that the changes in antral cells are
      primary to the onset of diabetes, and that the abnormalities observed in the
      antral cells in an animal model for diabetes type I might have relevance for the
      upper gastrointestinal dysfunction displayed in human diabetes.

PMID- 9590419
TI  - Prevalence of Barrett's esophagus in Hispanics is similar to Caucasians.
AB  - Barrett's esophagus (BE) is considered to be a disease of white males with a
      prevalence ranging from 0.5 to 4.0% in patients undergoing upper endoscopy (EGD)
      for any indication, and from 12 to 15% in patients with gastroesophageal reflux
      disease (GERD). The prevalence of BE in Hispanics is not known, but it is assumed
      to be lower. The aims of this study were to determine the prevalence of BE in
      Hispanic patients and to compare demographic and endoscopic characteristics with
      Caucasian patients with BE. Records of patients undergoing an EGD between October
      1993 and October 1996 were retrospectively reviewed. Patients were included in
      the study only if they had columnar-appearing esophageal mucosa at endoscopy and
      intestinal metaplasia with Alcian blue-staining goblet cells on biopsy. An
      extensive chart review was performed in patients with BE. There were 75 new cases
      of BE discovered: 60 (80%) were Caucasians, 6 (8%) Hispanics, 1 (1.4%) Native
      American, and 8 (10.6%) patients with either unknown or unconfirmed ethnicity. Of
      the 75 patients, 74 male, and the mean age was 65 +/- 11.4 years (range 36-92
      years). The prevalence of BE in Caucasians and Hispanics undergoing EGD for any
      reason was similar (5.3% and 3.8%, respectively, P = 0.563). The prevalence of BE
      in patients presenting with GERD symptoms was also similar between Caucasians and
      Hispanics (25% and 16%, respectively, P = 0.304). The two groups did not differ
      significantly with respect to age, symptoms, habits, or endoscopic findings. In
      conclusion, the prevalence of BE among Hispanic patients is similar to Caucasian
      patients, an unexpected finding.

PMID- 9590420
TI  - Role of nitric oxide in oxidative damage in isolated rabbit gastric cells exposed
      to hypoxia-reoxygenation.
AB  - The present study aimed to investigate the role of nitric oxide on the oxidative
      damage in isolated rabbit gastric cells exposed to hypoxia-reoxygenation. Nitric
      oxide synthesis modulators such as L-arginine and NG-nitro-L-arginine methyl
      ester, a nitric oxide donor, sodium nitroprusside, and superoxide dismutase were
      used to treat the cells, and the synthesis and secretion of mucus, lipid peroxide
      production, and glutathione contents of the cells were determined. As a result,
      hypoxia-reoxygenation decreased nitric oxide production and the synthesis and
      secretion of mucus, as well as glutathione contents of gastric cells, but hypoxia
      reoxygenation increased lipid peroxide production. Pretreatment with L-arginine,
      a substrate for nitric oxide synthase, sodium nitroprusside, and superoxide
      dismutase prevented the increase in lipid peroxide production and the decreases
      in glutathione contents, as well as the synthesis and secretion of mucus induced
      by hypoxia-reoxygenation. However, NG-nitro-L-arginine methyl ester, a nitric
      oxide synthase inhibitor, had no effect on these alterations. In conclusion,
      nitric oxide has an antioxidant defensive role on gastric cells by maintaining
      mucus and glutathione.

PMID- 9590421
TI  - Distinct effects of tetragastrin in rat gastroduodenal mucosa on mucin content
      and mucosal protective action against histamine-induced injury.
AB  - We examined the effects of tetragastrin on mucin (mucus glycoprotein) content and
      mucosal damage in the rat stomach and duodenum. Following an injection of
      tetragastrin (12, 120, or 400 microg/kg subcutaneously), no macroscopic damage
      was found to the gastric mucosa but an increase in corpus mucin content was
      noted, whereas mucosal lesions appeared and the mucin content decreased in the
      duodenum in a dose-related manner. In the groups with histamine (0.8, 8, or 80
      mg/kg intraperitoneally) administration, the extent of mucosal damage and the
      decrease in mucin content were dose-related in both these regions. For assessment
      of the effect of tetragastrin on the protective action in gastroduodenal mucosa,
      changes in mucin content and mucosal damage with histamine (80 mg/kg) -induced
      injury were examined. Coadministration of tetragastrin prevented the gastric
      mucosal damage and inhibited the decrease in corpus mucin content. In the
      duodenum, tetragastrin aggravated the histamine-induced mucosal damage and did
      not inhibit the reduction of the mucin content. From the present results, the
      increase in gastric mucins induced by tetragastrin might be related to the
      protective effect of gastric mucosa against injury. Tetragastrin did not protect
      the duodenal mucosa, and histamine-induced injury occurring in this region would
      be aggravated by the increase in HCl secretion and the decrease in mucin content
      induced by tetragastrin.

PMID- 9590422
TI  - Gastric volvulus as a cause of intermittent dysphagia.

PMID- 9590423
TI  - Eosinophil activation in ulcerative colitis: studies on mucosal release and
      localization of eosinophil granule constituents.
AB  - Activation of eosinophil granulocytes (eosinophils) seems to contribute to the
      pathophysiology of several inflammatory conditions. This process was evaluated in
      18 patients with ulcerative colitis and in 18 healthy controls using intraluminal
      segmental perfusion of the sigmoid colon and rectum and immunoanalysis for
      eosinophil cationic protein (ECP) in the perfusate. Immunohistochemistry for
      eosinophils and neutrophils was made in simultaneously taken biopsies and in
      biopsies from surgical specimens taken from additional 10 patients. The mucosal
      release of ECP was increased severalfold in patients with UC. The bowel biopsies
      demonstrated a lamina propria infiltrated with eosinophils. The degree of
      eosinophil activation/degranulation was related to the intensity of the
      inflammatory reaction. Activated eosinophils and extracellular deposits of ECP
      were, in particular, seen in crypt abscesses and in areas with damaged surface
      epithelium. Since ECP is highly cytotoxic, its release at the site of
      inflammatory bowel lesions might reflect a potential pathophysiological
      mechanism.

PMID- 9590424
TI  - Plasma and mucosal fatty acid pattern in colectomized ulcerative colitis
      patients.
AB  - Patients with inflammatory bowel disease (IBD) have increased plasma n3
      polyunsaturated fatty acids (PUFAs), which in ulcerative colitis (UC) patients
      persists six months after colectomy, suggesting a primary abnormality in fatty
      acid (FA) metabolism in IBD. This finding needed to be confirmed in a larger
      series of UC long-term colectomized patients. We aimed to assess the plasma FA
      pattern in UC colectomized patients with either Brooke's ileostomy (UC-BI) or
      ileal pouch anal anastomosis (UC-IPAA) and the mucosal FA pattern in the ileal
      reservoir of the UC-IPAA patients. Plasma FAs were assessed in 63 UC colectomized
      patients (31 with BI and 32 with IPAA) and 30 controls. In 26 UC-IPAA (8 with
      pouchitis and 18 without pouchitis) and in 13 healthy controls gut mucosal FAs
      were also investigated. FAs were detected by capillary column gas-liquid
      chromatography. Increased levels of saturated fatty acids (SFAs) and decreased
      percentages of monounsaturated fatty acids (MUFAs) were observed in both groups
      of patients. There were no changes in plasma n3 and n6 PUFAs. The mucosal FA
      pattern of the ileal reservoir consisted of increased long-chain PUFAs, specially
      n6 PUFA, and a decrease of their essential precursors. High percentages of SFAs
      and low percentages of MUFAs were also seen. The plasma FA profile previously
      described in IBD is not observed long-term after colectomy in UC, suggesting that
      it is related with the presence of inflamed intestine. High concentrations of
      SFAs and decreased percentages of MUFAs might represent early events in disturbed
      FA metabolism in IBD. The changes in FAs of the ileal reservoir, which closely
      resemble those found in human and experimental IBD, probably represent a common
      pattern of intestinal inflammation.

PMID- 9590425
TI  - Intestinal expression of human heat shock protein 90 in patients with Crohn's
      disease and ulcerative colitis.
AB  - Heat shock proteins are induced by several stress factors and are potential
      antigens in autoimmune disorders. Expression of heat shock protein 90 (HSP 90)
      was investigated in patients with inflammatory bowel disease and normal controls.
      We combined western blot analysis with laser densitometry for quantitation.
      Localization of HSP 90 was investigated by immunohistochemistry. Western blots
      showed a significant mucosal expression of HSP 90, which was comparable in
      patients and controls. There was also no difference between normal and inflamed
      mucosa in inflammatory bowel disease. In immunohistochemical staining studies,
      HSP 90 was detected in epithelial cells, mononuclear cells, giant cells, nerve
      cells, and endothelial cells of small vessels. There was no difference in the
      intensity of staining or localization in patients with inflammatory bowel disease
      compared to controls. These findings render a potential protective or immunogenic
      function of HSP 90 in inflammatory bowel disease unlikely.

PMID- 9590426
TI  - Glutathione content of colonic mucosa: evidence for oxidative damage in active
      ulcerative colitis.
AB  - Oxidative stress appears to play a role in the tissue damage of active ulcerative
      colitis, and it has been suggested that a defect in mucosal antioxidant defenses
      is a etiological factor in the disease. This study was undertaken to investigate
      the mucosal content and oxidation state of glutathione in ulcerative colitis in
      the active and inactive states and to examine the relationship between
      glutathione content and disease activity in this patient population. Endoscopic
      biopsies of colon mucosa were collected from normal subjects, from
      macroscopically normal tissue of patients with inactive and active ulcerative
      colitis, and from inflamed tissue of patients with active ulcerative colitis. The
      mucosal contents of GSH and GSSG were determined by liquid chromatography. We
      found no significant differences in tissue contents of reduced glutathione among
      the four groups. The median tissue level of oxidized glutathione in inflamed
      mucosa from patients with active ulcerative colitis was increased 1.7-fold (P =
      0.017) over that of patients with inactive disease. The oxidized glutathione
      content of the mucosa also showed significant positive correlations with clinical
      and histological indices of disease severity among ulcerative colitis patients.
      In conclusion, a change in the redox status of mucosal glutathione is associated
      with inflammation and disease activity in ulcerative colitis. This change appears
      to be a consequence of inflammation rather than a pathogenic factor for the
      disease.

PMID- 9590427
TI  - Sucrosemia in untreated celiac disease: a potential screening test.
AB  - During studies to develop serum tests of small intestinal permeability, we
      detected an unidentified disaccharide in HPLC traces of sera from untreated
      celiacs. This present study aimed to identify the disaccharide and determine
      whether the presence of the disaccharide in the serum after an oral challenge had
      potential as a simple screening test for celiac disease. The disaccharide was
      identified as sucrose by incubation studies of sera with disaccharidases. Twenty
      untreated celiacs, 15 treated celiacs, and 20 normal or dyspeptic controls were
      studied for the presence of sucrose in their serum after an oral load (8 g). The
      results in celiacs were compared with the presence of serum IgA endomysial
      antibodies. The 10 normal controls were also given a larger sucrose challenge (50
      g). Ten of the untreated celiacs and 10 controls had their brush border
      disaccharidase activities measured. Sucrose eluted in the same position as the
      unidentified disaccharide in the HPLC trace and the latter could be removed by
      incubation with sucrase. All untreated celiacs but none of the treated celiacs
      had sucrose in their serum after the 8-g oral challenge. None of the controls had
      sucrose in their serum after the 8-g or 50-g challenges. Three untreated celiacs
      were IgA endomysial antibody negative as were all the treated cases. Brush border
      sucrase activity was low in untreated celiac disease. The presence of sucrose in
      the serum after an oral load shows promise as a noninvasive test for celiac
      disease.

PMID- 9590428
TI  - Nerve terminals containing neuropeptides decrease in number after massive
      proximal small bowel resection in the piglet.
AB  - The aim of this study was to evaluate possible changes in the neuropeptide
      innervation pattern of the remaining porcine ileum following 75% proximal
      resection of the small intestine. Three-month-old piglets were operated on and
      two months postoperatively full-thickness specimens of the proximal part of the
      distal ileum wall were taken. Age-matched 3- and 5-month-old unoperated piglets
      were used as controls. The number and intensity of VIP-, galanin-, enkephalin-,
      substance P-, and somatostatin-containing nerve fibers were estimated in sections
      processed for immunofluorescence microscopy and subjected to quantitative
      scoring. The VIP-, galanin-, and enkephalin-immunoreactive fibers of the circular
      muscle layer and villi were also quantitated by computer-assisted morphometry.
      The number and intensity of VIP-immunoreactive fibers in the mucosa and circular
      muscle layer markedly decreased after resection as compared to 3-month-old and 5
      month-old controls (P < 0.05). The galanin immunoreactivity index decreased
      significantly after resection in the circular muscle layer as compared to both
      control groups (P < 0.05). The increase in the number of enkephalin
      immunoreactive nerve fibers that normally occurred from 3 to 5 months of age was
      inhibited by the resection. We were not able to see any differences in
      somatostatin or substance P immunoreactivity between the groups. The results
      suggest that massive resection induces significant changes in the neuropeptide
      containing innervation of the remaining small intestine. These findings are
      compatible with altered motor activity and mucosa function in the remain
      intestine.

PMID- 9590429
TI  - Premorbid hair growth over the trunk and severity of alcohol-related liver
      disease.
AB  - It is unclear why only a minority (<15%) of alcoholics develop liver disease. No
      predisposing host factor other than gender (women are more susceptible than men)
      has been identified. The present study was carried out to examine the association
      of another host factor, hair growth over the trunk, and alcoholic liver disease.
      Forty-four chronic alcohol abusers were categorized into group I (scanty hair
      growth) and group II (profuse hair growth) based on premorbid hair distribution
      over the trunk. The results of laboratory tests, liver histology, and incidence
      of portal hypertension were compared between the two groups. There were 21
      patients in group I and 23 in group II. The mean (+/- SD) daily alcohol
      consumption was greater in group II (230 +/- 146 g) vs group I patients (152 +/-
      56 g; P < 0.05), as was the duration of alcohol abuse (17.3 +/- 7.4 vs 11.9 +/-
      4.9 years; P < 0.01). Despite lower alcohol consumption, liver tests showed
      greater derangement in group I compared to group II patients. At histology,
      severe forms of liver damage were seen more frequently in group I vs group II
      patients (P < 0.001). Our results indicate a close association between the
      premorbid truncal hair growth and severity of alcoholic liver disease. These
      findings provide an easily recognizable clinical sign identifying individuals at
      increased risk of developing alcohol-related liver damage.

PMID- 9590430
TI  - Sodium butyrate-induced liver-type alkaline phosphatase activity in a small
      intestinal epithelial cell line, IEC6.
AB  - Sodium butyrate is a well-recognized differentiating agent inducing alkaline
      phosphatase activity, one of the epithelial differentiation markers. When IEC6
      cells, a nontransformed, small intestinal epithelial cell line, were cultured
      with butyrate, this substrate induced alkaline phosphate activity in a time- and
      dose-dependent fashion. However, the type of isoenzyme involved was a liver-type,
      not an intestinal-type. Electron microscopy revealed that the induced activity
      was strictly localized in the cytosol and not on the plasma membrane. However,
      disaccharidase activities, another kind of differentiation marker, were also
      enhanced by sodium butyrate. In addition, the positive cells demonstrating the
      presence of alkaline phosphatase activity were preferentially observed in tubular
      structures. These data show that butyrate-induced alkaline phosphatase activity
      is closely associated with differentiation-like phenomena in IEC6 cells, although
      the type of isoenzyme and cellular localization of the activity are different
      from those observed in mucosa.

PMID- 9590431
TI  - Solitary hepatic infantile myofibromatosis in a female adolescent.

PMID- 9590432
TI  - Spontaneous bacterial pleural empyema in liver cirrhosis.

PMID- 9590433
TI  - Physiological and induced neuronal death are not affected in NSE-bax transgenic
      mice.
AB  - Bax, a family member of the survival protein Bcl-2, is expressed in the nervous
      system during development and throughout adulthood. Bax deficiency has been
      demonstrated to prevent developmental and trophic factor deprivation-induced
      neuronal death. To further clarify the role of Bax in naturally occurring
      neuronal death and in neuronal death following apoptotic stimuli, we generated
      several lines of transgenic mice expressing the human Bax protein specifically in
      neurons, under the control of the neuron-specific enolase promoter. Transgene
      expression was first detected around E10.5 and E12.5, depending on the transgenic
      line. The total number of ganglion cells in the retina and of pyramidal cells in
      the hippocampus, both expressing the transgene, was similar in control and
      transgenic mice. In addition, in our model system, Bax overexpression did not
      appear to influence the in vitro survival of sensory neurons isolated from dorsal
      root ganglia after nerve grwoth factor (NFG) deprivation or the apoptotic death
      of motor neurons following axotomy.

PMID- 9590434
TI  - Prion protein fragment interacts with PrP-deficient cells.
AB  - A fragment of the prion protein (PrP106-126) induces cell death in cultures of
      wild-type embryonic day (E)16 mouse cortical neurons but not cells derived from
      mice devoid of cellular PrP(PrPo/o). Two common binding partners for PrP106-126
      expressed in both wild-type and PrPo/o mouse brain were isolated and their
      sequences determined. The two proteins were found to be alpha and beta tubulin.
      Further evidence that tubulin binds PrP106-126 within cells comes from cell
      culture experiments. Colchicine toxicity on PrPo/o mouse cortical cells is
      enhanced by PrP106-126 and taxol enhances toxicity of PrP106-126 on wild-type
      mouse cortical cells. Our evidence shows that a fragment of PrP can bind a
      cellular protein and in so doing, alters the metabolism of cells even when they
      do not express native PrP. This indicates that PrP106-126 is nontoxic to PrPo/o
      cells, not because of an inability to interact with these cells but because of
      the loss of some aspect of a PrP expression-dependent phenotype.

PMID- 9590435
TI  - Coding sequence and exon/intron organization of the canine CLN3 (Batten disease)
      gene and its exclusion as the locus for ceroid-lipofuscinosis in English setter
      dogs.
AB  - Hereditary ceroid-lipofuscinosis in English setters has been proposed to be the
      canine equivalent of human juvenile ceroid-lipofuscinosis, which results from
      defects in the CLN3 gene. Analyses were performed to determine whether the
      disease in English setters is also the consequence of a CLN3 gene mutation.
      Canine CLN3 cDNA was found to contain a 1,314-bp open reading frame predicting a
      derived amino acid sequence which is 89%, 85%, and 84% identical to the predicted
      amino acid sequences for the human, mouse, and rabbit CLN3 proteins,
      respectively. The canine gene has sixteen exons. No differences were detected
      when cDNA nucleotide sequences from an English setter with ceroid-lipofuscinosis
      and from a normal dog were compared. Moreover, alleles of the canine CLN3 gene
      distinguished by an intragenic marker segregated independently from the disease
      in an English setter family, eliminating CLN3 as the locus for the canine
      disease. A ceroid-lipofuscinosis-affected Tibetan terrier was homozygous for a
      Gly70Glu CLN3 variant; however, this allele is common in dog breeds considered
      free of ceroid-lipofuscinosis.

PMID- 9590436
TI  - Cytotoxic action of lindane in neocortical GABAergic neurons is primarily
      mediated by interaction with flunitrazepam-sensitive GABA(A) receptors.
AB  - The cytotoxic action of the gamma-isomer of hexachlorocyclohexane (y-HCH;
      lindane) was studied in cultured mouse neocortical neurons by measurements of the
      reduction in mitochondrial function using the MTT (3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyltetrazolium bromide) test. The cells were exposed to 30-300 microM
      lindane in the culture medium for different periods of time and lindane
      cytotoxicity was found to be time- and concentration-dependent. Lindane
      cytotoxicity could be ameliorated by addition of gamma aminobutyric acid (GABA)
      in a concentration-dependent manner but this effect of GABA was not blocked by
      bicuculline or picrotoxinin (PTX). Lindane induced cytotoxicity was also reduced
      by the GABA(A) receptor agonists muscimol and THIP (4,5,6,7
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol). This effect was enhanced by the
      simultaneous presence of flunitrazepam but only at the highest lindane
      concentrations studied (200 and 300 microM). Flunitrazepam by itself had no
      effect on lindane-induced cytotoxicity. The protective effect of GABA plus
      flunitrazepam was blocked by the benzodiazepine receptor antagonist flumazenil
      and by the GABA(A) antagonist bicuculline, suggesting the involvement of central
      benzodiazepine receptors allosterically coupled to the GABA recognition site at
      the GABA(A) receptor. When 100 microM PTX was used to suppress the protective
      effect of GABA and flunitrazepam, a significant effect of PTX was observed only
      at 300 microM lindane. The GABA(B) receptor agonist, baclophen, only marginally
      reduced the cytotoxic effect induced by the highest lindane concentrations. It is
      concluded that the cytotoxic action of lindane in neocortical neurons in culture
      is mediated primarily through an interaction with allosterically coupled GABA
      benzodiazepine recognition sites at the GABA(A) receptor.

PMID- 9590437
TI  - Cytotoxic action of lindane in cerebellar granule neurons is mediated by
      interaction with inducible GABA(B) receptors.
AB  - The cytotoxic action of the gamma-isomer of hexachlorocyclohexane (gamma-HCH,
      lindane) was studied in cultured mouse cerebellar granule neurons maintained in
      the presence or absence of the GABA(A) receptor agonist THIP (4,5,6,7
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol). The cells were exposed for 24 hr to
      lindane (30-300 microM) in the culture medium. Changes in mitochondrial function
      were investigated by using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) test. The results showed that lindane-induced
      cytotoxicity was concentration-dependent. In cerebellar granule cells not treated
      with THIP, lindane-induced cytotoxicity did not appear to be related to GABA(A)
      or GABA(B) receptors. However, in THIP-treated cultures, lindane-induced
      cytotoxicity was found to be mediated by an action of the insecticide on GABA
      receptors. In the latter case, GABA reduced the lindane-induced cytotoxicity, but
      the protective effect was not potentiated by flunitrazepam. The GABA(A) receptor
      agonist muscimol (50 microM) also protected the THIP-treated cultures against
      lindane-induced cytotoxicity. In addition, the GABA(B) receptor agonist
      R(+)baclofen protected the cells from lindane-induced cytotoxicity and the effect
      of baclofen was blocked by GABA(B) receptor antagonists. Pertussis toxin was
      found to reverse the protective effect of baclofen only at the highest lindane
      concentration (300 microM). The lindane-induced cytotoxicity could be partly
      explained as being secondary to excitotoxicity as a mixture of the excitatory
      amino acid receptor antagonists APV (D-(-)-2-amino-5-phosphonopentanoate) and
      CNQX (6-cyano-7-nitro-quinoxaline-2,3-dione) shifted the concentration-response
      curve for lindane-induced cytotoxicity to the right. It is suggested that the
      cytotoxic effects of lindane in THIP-treated cerebellar granule neurons are
      primarily related to an action of lindane on GABA(B) receptors and to a lesser
      extent on inducible low-affinity, benzodiazepine insensitive GABA(A) receptors.

PMID- 9590438
TI  - Sympathetic and sensory innervation of the extracerebral vasculature: roles for
      p75NTR neuronal expression and nerve growth factor.
AB  - The extracerebral vasculature receives a postnatal innervation of noradrenergic
      sympathetic axons and nociceptive sensory axons. These axons are responsive to
      the neurotrophin nerve growth factor (NGF), in that they possess the
      transmembrane receptors p140proto-trkA and p75neurotrophin receptor (NTR) which
      bind NGF. p75NTR-deficient mice display reduced patterns of sympathetic
      innervation of the pineal gland and sensory innervation of the skin (Lee et al.,
      1992, 1994a). The goal of this investigation was to determine whether an absence
      of p75 expression likewise perturbs the sympathetic and sensory innervation of
      the extracerebral vessels of adult mice, and if so, whether increasing levels of
      NGF within the target field is capable of enhancing this perturbed axon growth.
      Four lines of mice were used: wild-type C57Bl/6 mice, transgenic mice
      overexpressing NGF in the brain, p75NTR-deficient mice, and hybrid mice which
      overexpress NGF in the brain but lack p75NTR expression. Sympathetic and sensory
      innervation of the meningeal arteries were severely perturbed in p75NTR-deficient
      mice. Wild-type and hybrid mice displayed comparable patterns of sympathetic and
      sensory axons along the dural arteries. Transgenic mice, however, possessed the
      greatest degree of arterial innervation. These data reveal that while p75NTR
      expression may be a critical factor for initiating axon growth along the
      extracerebral vasculature during postnatal development, the sympathetic and
      sensory nervous systems display a remarkable degree of NGF-induced axonal
      plasticity, such that increased levels of NGF can ameliorate perturbed patterns
      of arterial innervation in p75-deficient mice.

PMID- 9590439
TI  - Ionic mechanisms in glutamate-induced astrocyte swelling: role of K+ influx.
AB  - L-Glutamate (L-GLU) induced astrocyte swelling in a time- and concentration
      dependent, as well as Na+- and Ca2+-dependent, and Cl(-)-independent manner.
      Swelling was prevented by MK-801, cystine, and ouabain. Since L-GLU swelling is
      ionically dependent, we determined the role of various ions in such swelling. Our
      results indicate that K+ uptake plays a major role in the mechanism of L-GLU
      induced astrocyte swelling. Like swelling, K+ uptake is dependent on Ca2+ and
      Na+, but not on Cl-. Likewise, K+ uptake was inhibited by MK-801, cystine, and
      ouabain. The K+ channel blockers, Ba2+ and tetraethylammonium, partially
      prevented L-GLU-induced swelling. In addition to K+ channels, K+ influx may also
      be mediated through Na+/K+-ATPase, as its activity is increased by L-GLU uptake
      along with the required Na+. Taken together, the data suggest that K+ influx
      plays a key role in the mechanism of L-GLU-mediated astrocyte swelling.

PMID- 9590440
TI  - Responses of young and aged rat CNS to partial cholinergic immunolesions and NGF
      treatment.
AB  - The cholinergic neurons of the basal forebrain (CNBF) are the major source of
      cholinergic innervation of the cortex and hippocampus. In Alzheimer's disease and
      aged brain, there are severe losses of cholinergic neurons in the nucleus basalis
      of Meynert, leading to a reduction of cortical cholinergic activity which
      correlates with the severity of cognitive deficits. While there is evidence that
      aged central nervous system (CNS) displays impaired stress response signaling,
      pharmacologic treatments with neurotrophic factors appear to ameliorate these age
      associated cholinergic deficits. To mimic these cholinergic deficits in
      experimental animals and study the acute effects of nerve growth factor (NGF), we
      induced a partial lesion of CBFNs by the intracerebroventricular (i.c.v.)
      injection of the cholinergic immunotoxin 192IgG-saporin, in groups of 3- and 30
      month-old rats. The lesion was followed 14 days later by i.c.v. administration of
      NGF, known to restore partial immunolesion-induced cholinergic deficits in rat
      CNS, and all rats were killed 2 days after the NGF treatment. Here we report the
      effects of partial immunolesions on the levels of choline acetyltransferase
      (ChAT) activity and NGF receptor mRNA levels in the basal forebrain of 3- and 30
      month-old rats. Because of their presence in the promoters of the NGF, NGF
      receptors, and ChAT genes, we also measured DNA-binding activity of the
      transcription factors NFB and AP-1 in the cortex and hippocampus. We discuss
      these findings in the context of endogenous NGF-mediated signal transduction
      mechanisms and conclude that we have evidence for age-associated decreases in
      endogenous NGF responses to partial deafferentation of the basal forebrain
      cholinergic projections.

PMID- 9590441
TI  - Activation of caspase-3 and apoptosis in cerebellar granule cells.
AB  - Caspase-3 activity increased dramatically in cytosolic extracts of rat cerebellar
      granule cells exposed to apoptotic conditions (basal medium Eagle (BME)
      containing 5 mM K+ without serum) when assayed with Ac-DEVD-amc, but not with Ac
      YVAD-afc, a preferred substrate for caspase-1. This provided a basis to examine
      relationships between enzyme activity and cell viability for purposes of
      selecting an optimal time for comparing neuroprotective agents or strategies.
      Exposure of neurons to an apoptotic medium containing 5 mM K+ in absence of serum
      led to a rapid 5- to 10-fold increase in caspase-3 within 2-4 hr but without
      significant cell loss, or morphological alterations. Exposure to apoptotic medium
      followed by replacement with maintenance medium containing 25 mM K+ and serum led
      to a rapid fall in caspase-3 and prevention of cell death. This strategy was not
      effective after 13 hr exposure despite a large fall in enzyme activity. These
      temporal changes infer systems for rapid enzyme turnover and/or activation of
      cytoplasmic components linked to later DNA degradation. The effects of
      cycloheximide point to requirements for protein synthesis, and those of Glu
      exclude a caspase-3 dependent pathway for necrotic cell damage. Brief treatment
      with 10 microM LIGA20, an anti-necrotic agent, also attenuated cell loss and
      caspase-3 activity, indicating a broad spectrum of neuroprotection. Rapid and
      long-lasting effects, together with its biophysical properties, suggest that this
      semisynthetic ganglioside acted upstream at or near a membrane site. As such,
      gangliosides provide useful agents to further probe pathways relevant to neuronal
      death in culture.

PMID- 9590443
TI  - Substructure and responses of cholinergic synaptic vesicles in the atomic force
      microscope.
AB  - The substructure and responses of individual 100-nm synaptic vesicles to osmotic
      stress have been probed with an atomic force microscope (AFM) operating in
      tapping mode. Cholinergic synaptic vesicles from the electric organ of Torpedo
      californica were imaged continuously as the osmolarity of the buffer was
      decreased. Vesicles in hyposmotic buffer lysed to form flat circular structures
      on the mica surface with a diameter about two times that of intact vesicles and a
      thickness of 7.2 +/- 1.7 nm, which can accommodate the lipid bilayer plus the
      internal proteoglycan. Images of intact vesicles in air reveal creases in the
      membrane surface. Phase mode AFM images of lysed vesicles in air show the
      presence of a material not seen on intact vesicles that might be intravesicular
      proteoglycan released from the membrane at very low osmotic and ionic strength.

PMID- 9590444
TI  - Expression and regulation of kainate and AMPA receptors in the rat neural tube.
AB  - We analyzed the expression and regulation of glutamate receptor subunits in the
      rat neural tube (10 day embryos) and in cell cultures derived from this tissue.
      In the cultures, all cells were stained with antibodies against the neural
      progenitor marker nestin. More than 50% of the cells were also stained by the
      monoclonal antibodies LB1 or A2B5, which bind to neuronal and glial progenitors.
      Approximately 6% of the cells were stained with antibodies for the low affinity
      NGF receptor, a neural crest cell marker. A small percentage of cells
      differentiated to neurons or astrocytes, as determined by staining with anti
      neurofilament and anti-GFAP antibodies, respectively. RT-PCR analysis of neural
      tube tissue and culture mRNAs demonstrated that the AMPA receptor subunits GluR3
      and 4 and the kainate receptor subunits GluR6, 7, KA1 and KA2 were detectable at
      E10. The kainate receptor subunits GluR6 and KA2 were upregulated by culture
      conditions which stimulated cell differentiation, as determined by concomitant
      downregulation of nestin mRNA. Both in neural tube tissue and in cultured cells,
      GluR6 was 100% unedited. Finally, both GluR6 and KA2 proteins could be detected
      in subpopulations of neural progenitors and differentiated neurons. Our data
      indicate that kainate receptor genes are expressed in undifferentiated progenitor
      cells of the neural tube at E10, and are upregulated during neural cell
      differentiation.

PMID- 9590442
TI  - Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss,
      following traumatic brain injury in the rat.
AB  - The neuroprotective effects of Riluzole, a compound with several mechanisms of
      action including the inhibition of sodium channel activity and glutamate release,
      were evaluated in a rat model of parasagittal fluid-percussion (FP) brain injury.
      Male Sprague-Dawley rats (350-400 g, n = 17) were anesthetized with sodium
      pentobarbital (60 mg/kg i.p.) and subjected to parasagittal FP brain injury of
      moderate severity (2.3-2.5 atm). Fifteen min following injury, animals randomly
      received an i.v. bolus of either Riluzole (8 mg/kg, n = 8) or vehicle (n = 9),
      followed by subcutaneous injections (identical dose) at 6 hr and 24 hr. Two weeks
      after injury and drug treatment, animals were sacrificed and a series of brain
      sections, stained with Hematoxylin and Eosin (H&E) or cresyl violet, were
      evaluated for quantitative cortical lesion volume and cell counts of hippocampal
      CA3 neurons, respectively, using a computerized image analysis system.
      Administration of Riluzole significantly reduced FP-induced tissue loss in the
      temporal/occipital cortices ipsilateral to the site of impact by 46%, compared to
      vehicle-treated, brain-injured animals (P = 0.01). In contrast, the selective
      neuronal loss observed in the CA3 region of the ipsilateral hippocampus was
      unaffected by Riluzole treatment. The present study demonstrates that Riluzole
      can attenuate cortical lesion size following brain trauma. These neuroprotective
      effects may be related to the synergy of the different mechanisms of action of
      Riluzole.

PMID- 9590445
TI  - Early diagnosis of familial nephropathy in English cocker spaniels.
AB  - Two litters of English cocker spaniels (ECSs) produced by familial nephropathy
      (FN) carriers were evaluated to characterize the early features of this disease.
      Three puppies developed FN. Proteinuria, which began when these puppies were five
      to-eight months old, was the first abnormality detected. Proteinuria persisted
      while each puppy's growth rate slowed, and renal function gradually deteriorated.
      The interval from onset of proteinuria to development of azotemia was two-to-nine
      months. Characteristic glomerular capillary basement membrane (GCBM) lesions were
      seen with transmission electron microscopy (TEM) of renal biopsy specimens
      obtained during this interval. Ultrastructural GCBM lesions progressed
      substantially during the interval from biopsy to necropsy. However, routine light
      microscopic findings did not allow definitive diagnosis of FN in either biopsy or
      necropsy specimens. Detection of FN can be accomplished by screening at-risk ECSs
      for proteinuria. Renal biopsies are required to confirm the diagnosis in dogs for
      which proteinuria cannot be explained otherwise. Percutaneous needle biopsy
      specimens sufficient for TEM must be used to examine the GCBM to make a
      definitive diagnosis.

PMID- 9590447
TI  - Diabetes mellitus, hyperadrenocorticism, and hypothyroidism in a dog.
AB  - An unusual combination of three endocrinopathies found in one dog is described. A
      six-year-old, spayed female, mixed-breed dog presented with polyuria, polydipsia,
      polyphagia, and weight loss. She was diagnosed with diabetes mellitus but was
      suspected of having insulin resistance and was diagnosed subsequently with
      hyperadrenocorticism. Persistent hypercholesterolemia led to the suspicion and
      eventual diagnosis of hypothyroidism. The dog has responded well to medical
      therapy, and her clinical signs and biochemical changes have resolved. A
      literature search did not identify a similar-reported polyendocrinopathy.

PMID- 9590446
TI  - Essential thrombocythemia in a dog: case report and literature review.
AB  - A 10.5-year-old, castrated male shih tzu was presented for evaluation of
      weakness, pica, and pallor of the mucous membranes. A hemogram indicated an
      inflammatory leukogram and a regenerative anemia with spherocytosis and
      thrombocytosis. The dog responded well to conservative therapy for immune
      mediated hemolytic anemia (IMHA). However, the thrombocytosis did not resolve.
      Serial hemograms were characterized by persistent thrombocytosis (platelet count,
      577,000 to 1,200,000/microl) with abnormal platelet morphology. A systematic
      investigation ruled out causes of physiological and reactive thrombocytoses. A
      diagnosis of essential thrombocythemia was made by fulfilling the criteria of the
      Polycythemia Vera Study Group of the National Cancer Institute. The marked
      thrombocytosis was nonresponsive to hydroxyurea therapy. The dog remains healthy
      despite the marked increase in the number of circulating platelets. A review of
      causes of thrombocytoses in humans and animals is presented, and the criteria for
      diagnosis of essential thrombocythemia are examined.

PMID- 9590448
TI  - Right-sided heart failure in a dog with primary cardiac rhabdomyosarcoma.
AB  - A seven-year-old, female German shepherd mixed-breed dog was presented with
      weakness, inappetence, and a distended abdomen. Right-sided heart failure with
      pleural, pericardial, and abdominal effusions; dyspnea; and tachycardia were
      identified. The radiographic and electrocardiographic examinations did not allow
      a conclusive diagnosis. Echocardiographic findings included a mass in the wall of
      both the right atrium and right ventricle, partially occupying the right heart
      cavities. A diagnosis of cardiac tumor was made, and the owner elected
      euthanasia. The necropsy confirmed a tumor mass located in the right atrium and
      right ventricle. A definitive diagnosis of primary cardiac rhabdomyosarcoma was
      based on histopathological and immunohistochemical analyses.

PMID- 9590449
TI  - Surgical reconstruction of severe cicatricial ectropion in a puppy.
AB  - A three-month-old chow chow mixed-breed puppy was presented with severe
      cicatricial ectropion of the upper eyelids after being burned maliciously. The
      burn wounds healed by second intention with contracture, causing eversion,
      elevation, and immobilization of the upper eyelids. The puppy was unable to blink
      or close the upper eyelids due to cicatrix (i.e., scar) formation. Surgical
      repair using tissue-relaxing procedures was successful in reducing corneal
      exposure and improving the puppy's appearance.

PMID- 9590450
TI  - Efficacy of parathyroid gland autotransplantation in maintaining serum calcium
      concentrations after bilateral thyroparathyroidectomy in cats.
AB  - Bilateral thyroidectomy is a commonly indicated treatment for feline
      hyperthyroidism. The most common postoperative complication is hypocalcemia due
      to disruption of the parathyroid glands. When parathyroid gland disruption is
      obvious, many authors suggest autotransplantation (AT) of the glands. This
      technique never has been supported by a scientific study which monitored
      postoperative calcium or parathyroid hormone (PTH) concentrations. Cats in this
      study each underwent bilateral thyroidectomy and parathyroid AT to mimic a
      clinical situation. Serum calcium concentrations normalized much quicker than
      concentrations in previously reported cats undergoing bilateral thyroidectomy and
      parathyroidectomy. Parathyroid AT greatly reduces morbidity in the
      parathyroidectomized cat.

PMID- 9590451
TI  - Complications associated with the implantation of polypropylene mesh in dogs and
      cats: a retrospective study of 21 cases (1984-1996).
AB  - Complications associated with implantation of polypropylene mesh in dogs and cats
      were evaluated retrospectively. Immediate postoperative complications were common
      (in 10 of 20 cases) but predominantly involved seroma formation which resolved
      with treatment. The only long-term (i.e., six months or more) complication
      identified was mass recurrence at the site of tumor resection (in seven of 14
      cases). Recurrence was affected by resection size. The average number of ribs
      resected in cases of thoracic wall neoplasia (with and without mass recurrence)
      was 1.8 and 3.5, respectively. In this study, implantation of polypropylene mesh
      facilitated the reconstruction of large tissue defects and was not associated
      with any serious complications.

PMID- 9590452
TI  - Comparison of sedative and cardiorespiratory effects of diazepam, acepromazine,
      and xylazine in ferrets.
AB  - The sedative and cardiorespiratory effects of an intramuscular injection of
      diazepam (3 mg/kg body weight), acepromazine (0.1 mg/kg body weight), or xylazine
      (2 mg/kg body weight) in ferrets (n = 10, crossover design) was evaluated. Time
      from injection to assuming lateral recumbency was not significantly different
      between the three drugs. Duration of recumbency expressed as mean+/-standard
      deviation was significantly longer with xylazine (68.3+/-20.8 min) than with
      diazepam (43.2+/-8.2 min) or acepromazine (49.8+/-11.2 min). Sedation was graded
      to be the best in the xylazine-treated ferrets and worst in the diazepam-treated
      ferrets. Analgesia was judged only to be present following xylazine injection.
      Systolic blood pressure, oxyhemoglobin saturation, and end-expired carbon dioxide
      (CO2) were similar with all three drugs. It was concluded that, at the doses
      administered, xylazine provided better chemical restraint in the healthy ferret
      than either acepromazine or diazepam.

PMID- 9590453
TI  - Evaluation of sedative and cardiorespiratory effects of diazepam-butorphanol,
      acepromazine-butorphanol, and xylazine-butorphanol in ferrets.
AB  - Ten ferrets were used in a crossover study to determine the sedative effects of
      intramuscularly (IM) administered diazepam (3 mg/kg body weight)-butorphanol (0.2
      mg/kg body weight), acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg
      body weight), or xylazine (2.0 mg/kg body weight)-butorphanol (0.2 mg/kg body
      weight). All ferrets became laterally recumbent following the administration of
      each drug combination. The xylazine-butorphanol combination caused a
      significantly longer (p less than 0.05) duration of analgesia than the diazepam
      butorphanol and acepromazine-butorphanol combinations. None of the ferrets could
      be intubated with any of the drug combinations. The time from induction to
      recovery was significantly shorter in the acepromazine-butorphanol-treated
      ferrets. A significantly lower heart rate was observed in the xylazine
      butorphanol-treated ferrets; however, an acceptable systolic blood pressure was
      maintained. Ventilatory function was more depressed in the diazepam-butorphanol-
      and xylazine-butorphanol-treated ferrets than in the acepromazine-butorphanol
      treated ferrets. Xylazine-butorphanol was found to be the best combination for
      use in ferrets.

PMID- 9590454
TI  - A prospective study of survival and recurrence following the acute gastric
      dilatation-volvulus syndrome in 136 dogs.
AB  - Dogs (n = 136) with gastric dilatation-volvulus (GDV) syndrome were followed over
      time to measure recurrence and mortality rates and to identify prognostic
      factors. Thirty-three (24.3%) died or were euthanized during the first seven
      days. Of 85 cases that were followed for up to three years, nine (10.6%) cases
      each had a recurrence of GDV and seven (8.2%) cases died or were euthanized. The
      median survival times for cases that had gastropexies and those that did not were
      547 and 188 days, respectively. Depressed or comatose cases on admission were
      three and 36 times, respectively, more likely to die than alert cases, while
      cases with gastric necrosis were 11 times more likely to die.

PMID- 9590455
TI  - Triple pelvic osteotomy: effect on limb function and progression of degenerative
      joint disease.
AB  - The objective of this study was to evaluate prospectively the outcome of 21
      clinical patients treated with triple pelvic osteotomies during the year
      following surgery. Specific aims included documenting the time of and extent of
      improved limb function as measured by force plate analysis, evaluating the
      progression of degenerative joint disease (DJD) in the treated and untreated
      coxofemoral joints, and determining whether or not triple pelvic osteotomy
      resulted in degenerative joint changes in the ipsilateral stifle and hock. Twelve
      dogs were treated unilaterally and nine dogs were treated bilaterally with triple
      pelvic osteotomies. There were no differences in mean anteversion angles, angles
      of inclination, or preoperative DJD between treated hips and untreated hips.
      Degenerative joint disease progressed significantly in all hips regardless of
      treatment. Two cases developed hyperextension of their hocks after the triple
      pelvic osteotomies. However, no radiographic evidence of DJD was observed for any
      of the stifles or hocks at any observation time. A significant increase in
      vertical peak force (VPF) scores was noted for treated legs by two-to-three
      months after surgery, which continued over time. Untreated legs did not show a
      significant change in VPF scores over time. No differences were found in
      progression to higher scores when unilaterally treated legs, first-side treated
      legs, and second-side treated legs were compared.

PMID- 9590456
TI  - Innovative drug treatments for viral and autoimmune myocarditis.
AB  - Myocarditis has been shown to be a common cause of cardiomyopathy and is believed
      to account for 25% of all cases in human beings. Unfortunately, the disease is
      difficult to detect before a myopathic process ensues. Treatment of myocarditis
      induced heart failure includes the standard regimen of diuretics, digoxin,
      angiotensin-converting enzyme inhibitors, and currently, beta-adrenergic
      blockers. Treatment of myocarditis itself is dependent on the etiology of the
      illness. Treatments under investigation include immunosuppressants, nonsteroidal
      antiinflammatory agents, immunoglobulins, immunomodulation, antiadrenergics,
      calcium-channel blockers, angiotensin-converting enzyme inhibitors, nitric oxide
      inhibition (e.g., aminoguanidine), and antiviral agents. Despite advances in
      treatment, more work needs to be done in the early detection of myocarditis.
      Additionally, better means need to be established for distinguishing between
      viral and autoimmune forms of the disease, so that appropriate treatment can be
      instituted.

PMID- 9590457
TI  - Performance of human mass balance studies with stable isotope-labeled drug and
      continuous flow-isotope ratio mass spectrometry: a progress report.
AB  - We propose performing human mass balance studies by administering stable isotope
      labeled (13C or 15N) drug and quantitating excess (above background) 13C or 15N
      in urine, serum, and feces by continuous flow-isotope ratio mass spectrometry (CF
      IRMS). Theoretical calculations and empirical data (dynamic range, linearity,
      sensitivity, precision, accuracy) are presented to establish that commercially
      available CF-IRMS instruments can quantitate stable isotope labeled (one or two
      15N or 13C labels) drug concentrations of 1.0 microg/mL or greater in urine,
      serum (15N), or feces. More than two 13C labels may be necessary to quantitate
      1.0 microg/mL of drug in serum. Three volunteers received 650 mg of 15N13C2
      acetaminophen, and urine was collected for 72 hours. Percent of administered
      label recovered in urine from the three subjects was 97.4, 78.9, and 95.4 for 13C
      and 90.3, 77.0, and 90.6 for 15N. Fecal recovery of label for one subject was
      0.9% (13C2) and 1.1% (15N). Serum pharmacokinetic values obtained by counting 13C
      or 15N in one subject were as expected for acetaminophen. This method appears to
      be promising, and further validation is ongoing.

PMID- 9590458
TI  - Application of population pharmacokinetics to the phase II development of an anti
      Alzheimer's disease compound, S12024.
AB  - Steady-state concentrations of S12024, a novel compound for treatment of
      Alzheimer's disease, were studied to determine the pharmacokinetic parameters of
      S12024 in Phase IIa patients and to assess the effect of patient characteristics
      on those pharmacokinetics. A prospective sparse sampling strategy was used to
      obtain oral repeated data (n = 285) from 89 patients, which were analyzed using a
      one-compartment model and the NONMEM computer program. The model suggested that
      apparent clearance of S12024 was influenced by the study and by patient age. In
      the Spanish study, apparent clearance was increased by 68% and 26% for doses of
      100 mg and 300 mg, respectively, and patient age decreased oral clearance by
      approximately 10% per decade in the patient age range (50 to 90 years). Data from
      only a few patients in the Spanish study were probably responsible for the
      observed study influence on apparent clearance of S12024, and no measured
      covariates could explain this effect. The model provided an excellent
      characterization of the observed data and it predicted correctly the plasma
      concentrations from an earlier Phase I trial and a subsequent Phase IIb study.
      The present model, built from Phase IIa data, provides a basis for examining the
      influence of patient covariates and the magnitude of their effects on the
      pharmacokinetics of S12024. The study effect is probably an artefact that will
      disappear by further expanding of the population model in the future.

PMID- 9590459
TI  - Development of a limited sampling approach in pharmacokinetic studies: experience
      with the antiepilepsy drug tiagabine.
AB  - A sparse sampling method is proposed to assess pharmacokinetic parameters after a
      single dose of the antiepilepsy drug tiagabine. Pharmacokinetic parameters
      obtained from two different pharmacokinetic studies were compared using sparse
      sampling (7 blood samples) with extensive sampling (15 to 16 blood samples). The
      results indicated that sparse blood samples taken at appropriate times can be
      used to estimate pharmacokinetic parameters as accurately as extensive blood
      samples. In addition, a limited sampling model (LSM) was developed using samples
      from 10 subjects at two time points (6 and 8 hours). The model was validated in
      40 subjects and provided good population mean estimates of area under the
      concentration-time curve (AUC) and maximum concentration (Cmax). The sparse
      sampling method described here can be used to assess pharmacokinetic parameters
      in drug development provided a prior knowledge of the pharmacokinetics of a drug
      has been obtained from extensive sampling. Further, the LSM described here may be
      useful in estimating AUC and Cmax of tiagabine using two samples in clinical
      settings. The LSM approach described here can also be used to estimate AUC and
      Cmax of a drug in preclinical toxicokinetic studies without detailed
      pharmacokinetic studies.

PMID- 9590460
TI  - Effects of extensive and poor gastrointestinal metabolism on the pharmacodynamics
      of pravastatin.
AB  - The enhanced nonenzymatic isomerization of pravastatin to SQ 31,906, a relatively
      inactive metabolite, has been demonstrated to occur on exposure to gastric
      acidity in humans. However, the effect of gastric metabolism on the
      pharmacodynamics of pravastatin has not been studied. In addition, it was
      hypothesized that some individuals may be more extensive gastric metabolizers
      than others. Sixteen men received 4 weeks of oral therapy with pravastatin 10 mg
      after a 6-week drug washout diet run-in period. Pharmacokinetic and
      pharmacodynamic parameters were determined after 8 hours of serum sampling on the
      final day of therapy. Patients with a metabolic ratio for area under the
      concentration-time curve (AUC0-8 of pravastatin/AUC0-8 of SQ 31,906) of less than
      1.6 had a significantly lower reduction in total and low-density lipoprotein
      (LDL) cholesterol compared with those with a ratio > 1.6. An enteric formulation
      of pravastatin should increase the bioavailability of pravastatin and enhanced
      lipid-lowering efficacy.

PMID- 9590461
TI  - Do alprazolam-induced changes in saccadic eye movement and psychomotor function
      follow the same time course?
AB  - The purpose of this study was to determine whether short-term tolerance develops
      to GABA-agonist-induced changes in saccadic eye movements (SEMs), and whether the
      time course for GABA-agonist induced onset and offset of impairment is similar
      for SEMs and for psychomotor function. An additional goal was to determine
      whether there are differences in sensitivity between SEMs and psychomotor
      function. Six healthy volunteers participated in this balanced double-blind,
      three-way crossover, single-dose study of placebo and two different dosage forms
      of the GABA-agonist alprazolam: a rapidly absorbed oral 1.5-mg compressed tablet
      (CT) and a 3.0-mg sustained release (SR) tablet. Treatments were separated by a 7
      day washout period. Peak concentrations did not differ between CT and SR
      treatments, although area under the concentration-time curve (AUC) of alprazolam
      was greater after administration of SR than after CT, because plateau
      concentrations were attained after SR. Both SEM and psychomotor tests showed time
      dependent responses consistent with the development of tolerance. SEMs
      discriminated the differences in rate of drug input of the CT and SR
      formulations, with impairment evident at low concentrations during absorption.
      SEM impairment also persisted longer than did psychomotor impairment. Peak
      saccade velocity is a more sensitive indicator of pharmacologic effects mediated
      by the GABA-benzodiazepine receptor complex than are psychomotor responses. This
      is probably the result of the very high GABA dependency of SEMs, along with their
      limited sensitivity to motivation.

PMID- 9590462
TI  - Pharmacokinetics and pharmacodynamics of irbesartan in patients with hepatic
      cirrhosis.
AB  - The effect of hepatic impairment on the clinical pharmacology of the angiotensin
      II (AII) receptor antagonist irbesartan was assessed by comparing pharmacokinetic
      and pharmacodynamic parameters in 10 patients with hepatic cirrhosis with a
      matched group of 10 healthy volunteers. The pharmacokinetics and pharmacodynamics
      of irbesartan, 300 mg taken orally once daily, were evaluated after single- and
      multiple-dose (7 consecutive days) administration to normotensive subjects in an
      open-label, multiple-dose, parallel group study. Pharmacokinetic data obtained
      after administration of single and multiple doses of irbesartan showed no
      significant difference between the two groups in time to maximum observed plasma
      concentration of drug (tmax), half-life (t1/2), area under the plasma
      concentration-time curve (AUC), apparent oral clearance (Cl(t)/F), renal
      clearance (Cl(r)), and accumulation index (AI). Steady-state levels of irbesartan
      were reached within 3 days in both treatment groups. After irbesartan
      administration on day 1, mean increases from baseline in plasma AII levels and
      plasma renin activity (PRA) were greater in the group with cirrhosis than in the
      control group. On day 7, mean increases from baseline in PRA were greater in the
      control group than in the group with cirrhosis. No discontinuations or serious
      adverse events occurred during the study. The pharmacokinetics of irbesartan
      after repeated oral administration were not significantly affected in patients
      with mild-to-moderate cirrhosis of the liver. No dosage adjustment is necessary
      in patients with hepatic insufficiency.

PMID- 9590464
TI  - Inhibition of capsaicin-induced cough by the gamma-aminobutyric acid agonist
      baclofen.
AB  - Gamma-aminobutyric acid (GABA) is a central inhibitory neurotransmitter that also
      exists in the lungs. The GABA-agonist baclofen has been shown to have antitussive
      activity via a central mechanism in animals. Recently it was demonstrated that a
      14-day course of baclofen given three times daily significantly inhibits the
      cough reflex in healthy volunteers. Because of the prolonged antitussive effect
      of baclofen that has been previously observed, the present study was conducted to
      evaluate the antitussive effect of low-dose, oral baclofen given once daily.
      Forty-one healthy volunteers were randomly assigned in a double-blind manner to
      receive a 28-day course of baclofen, either 10 mg or 20 mg once daily, or
      placebo. Subjects underwent cough challenge testing with inhaled capsaicin to
      establish baseline cough reflex sensitivity, and subsequently after 14 and 28
      days of therapy. Subjects receiving baclofen 20 mg daily demonstrated significant
      inhibition of cough sensitivity after 14 days and after 28 days of therapy
      compared with baseline. Neither placebo nor baclofen 10 mg daily had a
      significant effect on cough sensitivity. No serious side effects were experienced
      by any study participant. These results confirm the recent observation that
      baclofen has significant antitussive activity in humans. Further, once-daily
      administration of a relatively low dose of baclofen is sufficient to achieve
      significant cough inhibition, although at least 14 to 28 days of therapy may be
      required to attain maximal antitussive effect. These results support further
      investigation of baclofen or other GABA-agonists as potential therapeutic agents
      for chronic, nonproductive cough.

PMID- 9590463
TI  - A phase I/II evaluation of oral L-2-oxothiazolidine-4-carboxylic acid in
      asymptomatic patients infected with human immunodeficiency virus.
AB  - A randomized double-blind, placebo-controlled study was conducted in 37
      asymptomatic HIV-infected individuals (mean CD4 count 707 cells/mm3) to
      characterize the safety, pharmacokinetics, and effect on blood thiols of three
      dosage levels of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid (OTC;
      Procysteine; Clintec Technologies, Deerfield, IL). Single-dose administration of
      OTC resulted in measurable plasma levels at all dosages, with a mean peak plasma
      concentration of 734 +/- 234 nmol/mL at the highest dosage studied. After 4 weeks
      of administration three times daily, a statistically significant increase was
      seen in whole blood glutathione in the 1,500 mg and 3,000 mg dose groups compared
      with the placebo group. A significant increase in whole blood cysteine and
      peripheral blood mononuclear cell (PBMC) glutathione was not seen during the
      study period.

PMID- 9590465
TI  - Evaluating the safety of calcipotriene 30 g per day in patients with psoriasis: a
      parallel group, vehicle-controlled study.
AB  - Elevated blood and urine calcium levels have been reported with the use of high
      doses of calcipotriene ointment in patients with psoriasis. The objective of this
      study was to evaluate key measures of calcium metabolism in patients with
      psoriasis under supervised dosing conditions in a vehicle-controlled study. Of
      the 24 patients enrolled, 12 each were administered 15 g of ointment containing
      calcipotriene or vehicle twice a day for 14 days. Blood and urine samples and 24
      hour urine collections were obtained at selected time points. All 24 patients
      completed the study with no significant differences between treatments in any of
      the laboratory parameters. Trend analysis failed to show any significant
      differences over time with the exception of calcium, which showed significant
      changes common to both the calcipotriene and vehicle groups, suggesting that
      these changes were unrelated to treatment. The results of this study show that
      the use of calcipotriene ointment at a dose of 30 g per day for 14 days did not
      produce any significant alterations in blood or urine calcium concentrations and
      was well tolerated.

PMID- 9590466
TI  - KA 672-HCl, a neuronal activator against dementia: tolerability, safety, and
      preliminary pharmacokinetics after single and multiple oral doses in healthy male
      and female volunteers.
AB  - In vitro and animal experiments have characterized KA 672-HCl as a potent
      functional antagonist of excitatory amino acid-induced convulsions and mortality.
      In receptor-binding studies, the compound displayed high affinities to several
      serotoninergic, adrenergic, and dopaminergic receptors and to the sigma receptor.
      The potential for short- and long-term toxicity of KA 672-HCl in rats and dogs
      was found to be low. Double-blind, randomized, placebo-controlled studies were
      undertaken in healthy volunteers ranging from 52 to 74 years of age to determine
      tolerability, safety, and preliminary pharmacokinetics of single and repeated
      doses in humans. Single doses up to 40 mg were well tolerated, with no difference
      in effect from placebo. At 60 mg, approximately half of the volunteers
      experienced a moderate drug-related orthostatic syndrome. After repeated doses of
      10 or 20 mg KA 672-HCl for 14 days only minor adverse events of mild intensity
      were reported with no clear relation to dose or a clinically relevant difference
      from placebo. A mild decrease in semisupine and standing blood pressure 4 hours
      after administration was observed in the 20 mg group with no occurrence of
      orthostasis. Linear pharmacokinetics were observed after repeated doses. However,
      this was not the case after single-dose administration, as generally higher
      plasma concentrations were observed after the 20-mg dose than would have been
      predicted from the 10-mg data. The mean terminal phase half-life after the 20 mg
      dose was 11.1 hours and 13.7 hours after repeated and single doses, respectively.
      The safety and tolerability data support a continuation of therapeutic trials. KA
      672-HCl is currently entering phase II development.

PMID- 9590468
TI  - Eliminate the middleman.

PMID- 9590467
TI  - Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo
      controlled comparative clinical trial.
AB  - A double-blind, randomized, placebo-controlled, parallel-group, multicenter study
      was conducted to compare the effectiveness of an extended-release formulation of
      a classical antihistamine, brompheniramine, and a second-generation compound,
      loratadine, in the treatment of allergic rhinitis. Subjects with symptoms of
      allergic rhinitis received brompheniramine 12 mg twice daily (n = 112),
      loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7
      days. Study medications were blinded using a double-dummy technique. Subjects
      completed an overall evaluation of symptom relief on a daily basis and returned
      on treatment days 3 and 7, at which times the investigator assessed symptom
      severity. The investigator and subject each completed a global efficacy
      evaluation, and subjects were interviewed regarding adverse experiences. The
      primary efficacy variable was the physicians' global efficacy evaluation on day
      3. Symptoms also were analyzed as summed severity scores for all symptoms and for
      the nasal symptom cluster of rhinorrhea, sneezing, and nasal blockage. At all
      post-baseline evaluations (days 3, 7, and averaged over the two days),
      brompheniramine was significantly better than loratadine and placebo for both
      sets of summed symptom scores and all three global assessments. Loratadine was
      significantly better than placebo for physician ratings of total symptom severity
      averaged over the two days and for the physician and subject ratings of the nasal
      cluster on day 3. Central nervous system-related symptoms were the most
      frequently reported adverse experiences; somnolence was reported most frequently
      by patients taking brompheniramine, and its occurrence was less frequent as
      treatment continued. A nonprescription, extended-release formulation of
      brompheniramine 12 mg twice daily provided significantly better relief of
      symptomatic allergic rhinitis than loratadine 10 mg once daily.

PMID- 9590469
TI  - Formative years of the Urodynamics Society: reminiscences.
AB  - This paper traces the roots and foundations of the Urodynamics Society as a
      scientific urologic research society back to the postwar information explosion of
      the 1950s and 1960s. It describes the then-separate islands of science and
      urologic practice which gradually became amalgamated through interdisciplinary
      and crossprofessional collaborations and networks, aided by generous government
      subsidies and wise university policies.

PMID- 9590470
TI  - A computer model of the neural control of the lower urinary tract.
AB  - Better understanding of the underlying working mechanism of the neural control of
      the lower urinary tract will facilitate the treatment of dysfunction with a
      neurogenic cause. We developed a computer model to study the effect of a neural
      control system on lower urinary tract behavior. To model the mechanical
      properties and neural control, assumptions had to be made. These assumptions were
      based, as much as possible, on knowledge and hypotheses taken from the
      literature. With valid assumptions, it should be possible to simulate normal as
      well as pathological behavior. To test the computer model, first, normal behavior
      of the lower urinary tract was simulated, and secondly, the known features of
      bladder outlet obstruction were simulated after the properties of the urethra
      were changed. The simulation results are comparable with measured data, so the
      assumptions on which the model is based could be valid. If the assumptions are
      valid, the feedback loops used in the model are also important feedback loops in
      vivo, and the model can be used to gain insight into the underlying mechanism of
      neural control.

PMID- 9590471
TI  - Myogenic changes of the levator ani muscle in premenopausal women: the impact of
      vaginal delivery and age.
AB  - The aim of this study was to evaluate the impact of parity and age on
      histomorphology of the pelvic floor muscles in female cadavers of reproductive
      age and to find out whether there is evidence of myogenic or neurogenic muscle
      injury. In a cross-sectional study 45 premenopausal unfixed and fresh female
      cadavers were studied. Four groups were defined: nulliparous and parous women
      under the age of 40 and over 40 years of age. The pelvic floor was biopsied at
      six standardized locations. For evaluation of the quantitative parameters and
      fiber type identification, actomyosin ATPase at pH 9.4 was used. For
      histomorphological evaluation, sections were stained with hematoxylin/eosin, van
      Gieson, and Gomori trichrome. The circumference of type I fibers is significantly
      larger in nulliparous women younger than 40 years compared to nulliparae older
      than 40 years. Comparing these groups, the form factor of type II fibers also
      increases significantly, presenting a more circular cell form. Compared to
      nulliparae, vaginal delivery led to a significant difference regarding the
      presence of centrally located nuclei, fibrosis, and variation in fiber diameter.
      In nulliparous women, these significant changes were also found with increasing
      age. In women with a history of vaginal delivery, no further increase in these
      characteristics could be detected with increasing age. Comparing the three
      different biopsy sites, all three changes were more pronounced in the ventral
      part. There was no evidence of grouped fiber atrophy, small angulated fibers, or
      type grouping in any of the biopsy specimens. Aging and vaginal childbirth lead
      to histomorphological changes of the pelvic floor muscle that are consistent with
      changes of myogenic origin. Evidence of neurogenic damage could not be
      demonstrated.

PMID- 9590472
TI  - Micturitional disturbance in a patient with adrenomyeloneuropathy (AMN).
AB  - We report a case of adrenomyeloneuropathy (AMN) in which serial urodynamic
      studies showed neurogenic bladder dysfunction. The patient was in good health
      until the age of 12, when he began to lose his hair. At age 25 he started to have
      urinary urgency, difficulty in voiding, occasional fecal incontinence, erectile
      impotence, and progressive gait disturbance. In his first admission to our
      hospital age 31, he was intelligent but childish. He showed diffuse baldness,
      spastic paraparesis, and disturbed vibratory sensation. Serum cortisol response
      to corticotropin (ACTH) was low and serum levels of very long chain fatty acids
      were increased. Nerve conduction studies and sural nerve biopsy showed the
      presence of peripheral neuropathy. These findings confirmed the diagnosis of AMN.
      The first urodynamic study showed residual urine volume of 50 ml, impaired
      bladder sensation, and detrusor hyperreflexia. At age 38 he needed diapers
      because he became apathetic and demented, and could no longer stand by himself.
      MRI disclosed high signal intensities in the bilateral cerebral white matter. The
      second urodynamic study showed residual urine volume of 200 ml and decreased
      bladder capacity with marked detrusor hyperreflexia. Demyelinating lesions of the
      peripheral nerve and white matter of the spinal cord and the cerebrum may be
      mainly responsible for the micturitional disturbance in our patient with AMN.

PMID- 9590473
TI  - Effect of alpha1 adrenoceptor antagonist on the urodynamics of the upper and
      lower urinary tract of the male rat.
AB  - In this investigation, we examined the impact of the alpha1 adrenoceptor (alpha1
      ADR) antagonist prazosin on the urodynamic characteristics of upper urinary tract
      function and associated micturition characteristics of the adult male rat. The
      focus of the study was to evaluate the extent to which prazosin affects urine
      production and ureteral transport relative to its effect on micturition. Control
      micturition studies were first performed using 28 awake Sprague-Dawley rats that
      were placed in metabolic cages for characterization of the frequency and mean and
      total volume voided over a 4-hr period. Following the control studies, the effect
      of intraperitoneal prazosin, 30 microg/kg, was evaluated under identical
      conditions. Urodynamic studies were done to identify the bladder filling and
      voiding characteristics of anesthetized rats that were infused with saline at a
      rate of 0.22 ml/min. From the urodynamic studies the parameters of bladder
      pressure (Pves) and volume (V) during filling, urethral opening (Puo) measured at
      the moment of micturition, and maximum detrusor pressure during voiding (Pdetmax)
      were evaluated. External sphincter electromyography was also monitored and
      recorded together with bladder pressure during voiding. Renal pelvic pressure was
      measured via a nephrostomy catheter and recordings were made simultaneously with
      bladder filling and voiding. The upper urinary tract was visualized using
      microscopic video imaging of the ureter, contrasted by perfusing the renal pelvis
      with indigo carmine. Characterization of upper tract transport was made in terms
      of renal pelvic pressure, ureteral peristaltic rate, and bolus length and
      velocity. The results show that in the awake rat, 30 microg/kg of prazosin
      decreased the urine production rate from 4.8 +/- 0.074 to 1.6 +/- 0.23 ml (P <
      0.001) and micturition frequency by a similar proportion from 1.99 +/- 0.44 to
      0.53 +/- 0.08/hr. In the lower urinary tract, prazosin did not change the
      baseline pressure of the bladder but produced significant dose-dependent
      decreases in Pdetmax, Puo, and frequency of micturition. In the upper urinary
      tract, ureteral and pelvic frequencies decreased, whereas the length of bolus
      increased significantly corresponding to increased doses of prazosin. These
      results suggest that, although prazosin facilitates micturition by reducing
      urethral opening pressure, it also reduces the rate of urine production and
      modulates the function of urine transport in the upper urinary tract.

PMID- 9590474
TI  - Use of abdominal fascia to create partial outlet obstruction in rabbits.
AB  - Partial outlet obstruction has been used for a considerable period of time as an
      animal model for the urodynamic changes that occur with the progressive
      obstruction of benign prostatic hyperplasia (BPH). Although there are many models
      of partial outlet obstruction, one common feature is that the degree of
      obstruction produced is inconsistent. The current study evaluates the responses
      of the bladder to a partial outlet obstruction created using an autologous
      fascial collar from harvested rectus fascia. The results demonstrate that
      although there was a moderate and variable increase in bladder mass, the
      alterations in the contractile responses to field stimulation (FS), carbamyl
      choline (carbachol), KCl, and adenosine 5'-triphosphate (ATP) were less severe
      than other models of partial outlet obstruction. Specifically, there was an
      approximate 40% decrease in the magnitude of the contractile response to FS but
      no significant changes in the magnitude of the contractile responses to
      carbachol, KCl, or ATP. Further analysis of the contractile responses
      demonstrated that there was a greater decrease in the rate of tension generation
      than in the magnitude of response for FS, and a significant increase in the time
      to maximal tension. Although there were no decreases in the magnitude of the
      responses to carbachol, KCl, or ATP, there were significant reductions in the
      rate of tension generation for carbachol and KCl and significant increases in the
      time to maximal tension for carbachol and ATP. Applying less tension over a wider
      area, the fascial collar provided a consistent and reproducible mild partial
      outlet obstruction.

PMID- 9590475
TI  - The effects of delayed hormone replacement therapy on estrogen receptors of the
      cynomolgus monkey bladder and vagina.
AB  - The aim of this study was to determine cytosolic estrogen receptor content of the
      cynomolgus monkey bladder and vagina after hormone replacement therapy. Animals
      maintained without hormone therapy for 2 years after surgical menopause were
      randomized to receive either no hormones (OVX), conjugated equine estrogens
      (CEE), or estrogen/medroxyprogesterone acetate (CEE + MPA) treatment for 30
      months. Estrogen receptor content of bladder and vagina cytosolic extracts was
      determined using a commercial enzyme-linked immunosorbent assay. Estrogen
      receptors were uniformly present, although the vaginal concentration was 100-fold
      greater than in the bladder. Estrogen and combination therapy significantly
      decreased cytosolic receptor content in both sites compared with controls. The
      cynomolgus urogenital tract remains estrogen sensitive 2 years after surgical
      menopause. Prolonged exposure to estrogens decreases cytosolic estrogen receptor
      content in a manner similar to that described for short-term estrogen therapy.
      These results suggest that the effects of hormone replacement on the urinary
      tract can be identified even if initiated years after menopause.

PMID- 9590476
TI  - Standardization of outcome studies in patients with lower urinary tract
      dysfunction: a report on general principles from the Standardisation Committee of
      the International Continence Society.

PMID- 9590477
TI  - Outcome measures for research in adult women with symptoms of lower urinary tract
      dysfunction.

PMID- 9590478
TI  - Outcome measures for research in treatment of adult males with symptoms of lower
      urinary tract dysfunction.

PMID- 9590479
TI  - Outcome measures for research of lower urinary tract dysfunction in frail older
      people.

PMID- 9590480
TI  - Comment on "Relationship between urethral and vaginal pressures during pelvic
      muscle contraction," Neurology and Urodynamics (1997):16:553-558.

PMID- 9590481
TI  - Exercise testing in cystic fibrosis.

PMID- 9590482
TI  - Reproductive health in males with cystic fibrosis: knowledge, attitudes, and
      experiences of patients and parents.
AB  - Males with cystic fibrosis (CF) are generally infertile as a result of aberrant
      development of Wolffian duct derivitives. The personal significance of this and
      related reproductive and sexual health (RSH) issues is unknown. We set out to
      describe the knowledge, attitudes, and experiences regarding RSH in a group of
      adolescent and adult males with CF, as well as the knowledge and attitudes of
      parents. This descriptive study was based on a semi-structured interview
      utilizing in-depth interview techniques. Questions included aspects of knowledge,
      attitudes, and experiences. Adolescent (aged 14-17 years) and adult (at least 18
      years) males attending the Children's Hospital Cystic Fibrosis Clinic, Boston,
      MA, USA, or hospitalized at the Children's Hospital over that period were
      eligible; the accompanying parent of the adolescent was also interviewed.
      Consecutive eligible males were interviewed over a 3 month period. Summary data
      are presented, attitudinal data are analyzed qualitatively, and a selection of
      representative transcript data are reported to describe the range of opinions.
      Fifty males (10 adolescents, 40 adults) participated; this constituted a
      consecutive sample of 44% of the eligible clinic population. Ninety percent of
      adults, 60% of adolescents, and 50% of parents knew of male infertility. The mean
      age (+/-SD) at which adults recalled first hearing this was 16.0 +/- 4.7 years
      and 13.9 +/- 1.6 years for those adolescents who knew of infertility. Nineteen
      (48%) of adults and 5 (83%) of adolescents first heard about infertility from
      their health care providers. Ninety percent reported no major distress upon first
      hearing about infertility during adolescence. Increasing significance of
      infertility with maturity was reported by 12 men (30%); only 4 adults (10%)
      reported that infertility was not a significant aspect of CF. Forty percent knew
      that males with CF have a small volume ejaculate, but none had been told this by
      a health care provider. Thirty percent of men had semen analysis performed and
      all were azoospermic. We conclude that the majority of males with CF know of
      likely infertility. The significance of this knowledge changes with time. Poor
      knowledge and confusion surround a range of RSH issues in males with CF.

PMID- 9590483
TI  - The "worth" of routine spirometry in a cystic fibrosis clinic.
AB  - In our cystic fibrosis clinic, all patients older than 6 years perform spirometry
      at each visit just before being seen by the health care team. Upon review, we
      determined that our perceived rationale for this practice was that the medical
      history fails to detect deterioration in a sizable minority of patients whose
      pulmonary decline can be detected by spirometry. Furthermore, the literature and
      our own experience indicates that physical examination frequently will not detect
      changes in pulmonary status until the changes are advanced. As part of an ongoing
      quality/cost assessment, we decided to challenge our rationale for performing
      routine spirometry. Using standard methodology, we developed a six-item Likert
      style questionnaire, the purpose of which was to assess perceived changes in
      pulmonary symptoms since the last clinic visit. The questionnaire had an
      acceptable degree of internal consistency (Cronbach's alpha = 0.92), although the
      question about sputum production showed the least correlation with responses to
      other items. We administered the questionnaire to 103 consecutive different
      patients and examined the association between reported changes in symptoms and
      actual changes in spirometric outcomes. Overall, there was a statistically
      significant, but clinically weak association between symptom scores and change in
      FEV1, r2 = 0.16, P < 0.001. Twenty-three patients had a decline in FEV1 of > or =
      10% from one clinic visit to the next. Depending on the method used to place
      symptom scores into categories indicating that pulmonary symptoms were "worse,"
      "same," or "better" than at the last clinic visit, 40-60% of these 23 patients
      indicated they felt the "same" or "better." We conclude that spirometry is a
      justifiable part of all clinic visits for patients with cystic fibrosis, assuming
      that one would want to detect and treat declines in pulmonary status before they
      become advanced.

PMID- 9590484
TI  - Determinants of reproducibility of lung function tests in children aged 7 to 10
      years.
AB  - Lung function (LF) tests are part of many investigations in childhood lung
      disease. However, individual reproducibility of LF will confound between-subject
      differences. At the same time, increased LF variability has been linked to
      respiratory disease. In a sample of 598 children, two LF tests, separated by a 5
      min interval, were recorded, and reliability (Rel) of forced expiratory volume in
      1 s (FEV1), forced vital capacity (FVC), and maximal expiratory flow at 50% of
      FVC (MEF50) was determined. Rel was also assessed in children trained and
      untrained in the performance of LF. To investigate determinants of
      reproducibility for FEV1, the absolute difference between two repeated tests was
      calculated. Whenever this difference was > 120 ml, a child was considered to
      demonstrate excessive variability (poor reproducibility) in FEV1. For volume
      parameters coefficients of reliability (Crel) were found to be better than for
      MEF50 (FEV1: 0.96; FVC: 0.94, MEF50: 0.91). In untrained children Crel for FEV1
      was only 0.91, but it was increased in subsequent visits (0.98, 0.97, and 0.97 at
      the second, third, and fourth tests, respectively). Excessive variability in FEV1
      was observed in 10% of children and was related to the presence of wheeze [odds
      ratio (OR) 6.31; 95% confidence interval (CI) 1.78-22.4), shortness of breath (OR
      3.14; 95% CI 1.00-9.93), a diagnosis of asthma (OR 6.25; 95% CI 1.76-22.1), and
      bronchial hyperresponsiveness (OR 4.30; 95% CI 2.07-8.94). We conclude that
      increased variability of LF is likely to be present in young children not
      accustomed to the testing procedure and in children with respiratory symptoms.
      Therefore, before guidelines for LF testing are applied, children should be
      trained to perform the tests and we should be cautious in the interpretation of
      test results in children who present with symptoms.

PMID- 9590485
TI  - Influence of epidermal growth factor and transforming growth factor beta-1 on
      patterns of fetal mouse lung branching morphogenesis in organ culture.
AB  - Transforming growth factor-beta (TGF-beta), a potent inhibitor of epithelial cell
      proliferation, and epidermal growth factor (EGF), a mitogenic polypeptide that
      binds to cell surface receptors, are important regulators of cell
      differentiation; however, their distinct role(s) in lung development and their
      mechanisms of action are not well understood. We evaluated the effects of these
      factors on lung morphogenesis in murine fetal lungs at gestational day 14
      (time:zero) and again after 7 days in culture. Baseline controls were cultured
      after tracheal transection in supplemented BGJb medium, and other tracheally
      transected lungs were cultured following addition of EGF (10 ng/ml BGJb), TGF
      beta1 (2 ng/ml BFJb), or with both in combination added to the medium. The
      control lungs in culture had poorly developed airways and an absence of defined
      acinar structures. The addition of EGF resulted in hyperplasia of primary airways
      with stunted outgrowths, monopodial branching, and absence of distinct acinar
      structures. Addition of TGF-beta1 alone, led to significant elongation of primary
      airways, without normal airway branching; however, terminal dipodial branching
      was seen and the prospective pulmonary acini were well defined. Combination of
      these growth factors (GF) resulted in a more normal branching pattern and
      differentiation, suggesting their epigenetic role in lung morphogenesis and
      mutual interactive mechanisms that regulate lung development. These lungs had
      more abundant and larger lamellar bodies than those after other treatments.
      Control lungs remained immature with prominent glycogen aggregates with
      occasional dense lamellar bodies. The total protein and DNA contents were highest
      with EGF treatment, followed by combination treatment; these observations were
      supported by immunohistochemical localization of proliferating cell nuclear
      antigen, an indication of the proliferative state of tissues. All the surfactant
      proteins were relatively unaltered and their messages were up-regulated for SP-A,
      but down-regulated for SP-B and SP-C in the lungs treated with growth factors. In
      conclusion, we have demonstrated enhanced biochemical and structural development
      of lungs treated in vitro with GF, and propose that further research in this area
      may lead to therapeutic uses of GF alone or in combination with other agents for
      the treatment of newborn respiratory distress due to lung immaturity or
      hypoplastic lung development.

PMID- 9590486
TI  - Effect of antenatal tracheal occlusion on lung development in the sheep model of
      congenital diaphragmatic hernia: a morphometric analysis of pulmonary structure
      and maturity.
AB  - The incidence of congenital diaphragmatic hernia (CDH) is 1:1,207-5,000, and the
      condition is associated with high mortality and morbidity, attributed principally
      to associated pulmonary hypoplasia. Repairing the diaphragmatic defect by
      antenatal surgery has high mortality, mainly due to premature labor. Antenatal
      tracheal occlusion, which is achievable by less invasive methods, stimulates lung
      growth (weight and DNA). However, its effectiveness in reversing structural and
      maturational abnormalities and its optimal timing requires further investigation.
      We hypothesized that (1) antenatal tracheal occlusion performed in the lamb model
      of congenital diaphragmatic hernia will stimulate lung growth and structural
      development and restore lung structure and maturity toward normal levels by term
      gestation; (2) effects will be detectable by morphometric measurements of the
      following parameters: lung volume, ratio of parenchyma to nonparenchyma, volume
      density of connective tissue within nonparenchyma, ratio of gas exchange tissue
      to airspace in parenchyma, gas exchange surface area, capillary loading,
      alveolar/airspace density and alveolar perimeter; (3) effects will be seen in all
      lobes of the lung; and (4) a greater effect will be observed when tracheal
      occlusion is performed early rather than late in gestation. Fourteen lambs
      underwent CDH creation at gestation day 72-74 followed by tracheal occlusion at
      day 101 (n = 7) or 129 (n = 7). They were delivered by Cesarean section at 143
      days (term = 145-149). Lungs were obtained at autopsy, inflation fixed, divided
      into lobes, and sampled; morphometric analysis was performed. Comparisons were
      made with previously reported results from control lungs of normal lambs and
      lambs with untreated CDH. In comparison with untreated lungs, antenatal tracheal
      occlusion at both times resulted in increased volumes for total lung and lobes,
      increased volume density of parenchyma and of airspace within parenchyma, and
      increased gas exchange surface areas. Normal values for gas exchange surface area
      density, and alveolar density and perimeter were attained and the lungs appeared
      more mature than non-occluded lungs. Tracheal occlusion earlier in gestation
      produced a greater effect, achieving greater than normal values for lung volumes
      and volume densities, whereas the capillary loading value was similar to normal
      lung. Later occlusion achieved less than normal values for lung volumes and
      volume densities, with a reduced capillary loading value. We conclude that
      antenatal tracheal occlusion is capable of reversing structural total lung and
      lobar hypoplasia and immaturity caused by CDH as determined by morphometrically
      determined parameters. The effect is greater when tracheal occlusion is performed
      early rather than late in gestation. The results are encouraging for development
      of treatment methods for humans with antenatally diagnosed CDH.

PMID- 9590487
TI  - Effects of rate and amplitude of breathing on respiratory system elastance and
      resistance during growth of healthy children.
AB  - Intrinsic properties of lung and chest wall tissues can lead to breathing rate
      (frequency [f]) and amplitude (tidal volume [VT]) dependence of respiratory
      system resistance (R) and elastance (E). To explore these dependencies on R and E
      within physiological limits of tidal volume and breathing frequencies during
      early childhood. we measured airway opening pressure (Pao) and flow (V'ao) in 15
      anesthetized, paralyzed, intubated, and mechanically ventilated healthy children
      (age 1 day to 72 months; weight 2.5-21 kg) at multiple combinations of VT (6, 10,
      and 14 mL/kg) and frequency (10, 20, and 30 breaths/min). In each instance, R and
      E were estimated by multiple linear regression applied to the tracheal pressure,
      flow, and volume (V), assuming a simple series R-E model. R decreased
      substantially with increasing frequency and weight (Wt), but was unaffected by
      changes in VT (R = 764Wt(-0.91) x f(-0.57)). E decreased sharply with increasing
      Wt, was lower at higher VT, and was slightly, yet significantly, increased at
      higher frequency (E = 2,905Wt(-1.38) x VT(-0.18) x f(0.11)). Such frequency
      dependence of R and E is consistent with stress adaptive, or viscoelastic,
      properties of respiratory tissues. The small V dependence of E is similar to that
      observed in other species under healthy conditions and presumably reflects the
      combined nonlinear pressure-volume relationships of the healthy parenchymal and
      chest wall tissues. Lack of VT dependence of R at high inspiratory flow rates
      suggests that turbulent flows are either not an important form of energy
      dissipation in the lower airways of children or they are counterbalanced by a
      decrease in tissue damping at high VT. The above regression models represent the
      first attempt to quantify simultaneously the separate effects of lung growth as
      well as rate and amplitude of breathing on R and E. Similar equations based on a
      larger sample of healthy subjects can provide normative R and E values for
      comparison with mechanically ventilated children with lung disease.

PMID- 9590488
TI  - A step in the right direction: assessing exercise tolerance in cystic fibrosis.
AB  - Exercise tolerance may be reduced in patients with cystic fibrosis, but it is not
      always possible to predict this from standard lung function measurements. Formal
      exercise testing may, therefore, be necessary, and the test should be simple and
      readily available. We have developed a "3-minute step test" and compared it with
      the standard 6-minute walking test. Subjects stepped up and down a 15-cm-high
      single step at a rate of 30 steps per minute for 3 minutes. The effect of the
      step test on spirometry was tested first in 31 children with CF (mean age, 12.0
      years), who had a mean (range) baseline forced expired volume in 1 second (FEV1)
      of 64% (18-94%) of predicted values. The step test was then compared with the
      standard 6-minute walk in a further 54 patients with cystic fibrosis (mean age,
      12.5 years), with mean (range) baseline FEV1 of 61% (14-103%) of predicted
      values. Outcome measures were minimum arterial oxygen saturation (SaO2), maximum
      pulse rate, and the modified Borg dyspnea score. Post-step test spirometry showed
      mean (95% CI) changes of -1.1% (-6.0 + 3.9%) for forced vital capacity, of -1.6%
      (-4.2 + 1.1%) for FEV1, and +0.25% (-2.8 + 3.3%) for peak expiratory flow,
      although 5/31 children showed >15% drop in one or more parameters. The step and
      walk tests both produced significant changes (P < 0.0001) in all outcomes, with a
      mean (range) minimum SaO2 of 92% (75-98%) versus 92% (75-97%), a maximum pulse
      rate of 145 b.p.m. (116-189) versus 132 (100-161), and a Borg score of 2.5 (0-9)
      versus 1.0 (0-5), respectively. Comparison of the two tests showed that the step
      test increased breathlessness (mean change Borg score, 2.3 vs. 0.8; P < 0.0001)
      and pulse rate (mean change, 38% vs. 24%, P < 0.0001) significantly more than the
      walk, whereas the decrease in SaO2 was similar (mean change, -2.9% vs. -2.6%; P =
      0.12). Some patients with a significant drop in SaO2 (>4%) would not have the
      decrease predicted from their baseline lung function. Reproducibility for the two
      tests was similar. The step test is quick, simple and portable, and is not
      dependent on patient motivation. Although the step test is more tiring, its
      effect on SaO2 is similar to the 6-minute walking test. It is a safe test that
      may prove to be a valuable measure of exercise tolerance in children with
      pulmonary disease, although longitudinal studies are now needed.

PMID- 9590489
TI  - Tuberculous broncho-esophageal fistula in children: a description of two cases.

PMID- 9590490
TI  - Tempo of hematologic recovery correlates with peripheral blood CD34+ cell level
      in patients undergoing stem cell mobilization.
AB  - This study was undertaken to evaluate the relationship between the time to
      recovery of peripheral blood counts and CD34+ cells in the peripheral blood (PB)
      and apheresis collections of patients undergoing intensive chemotherapy followed
      by rhG-CSF. Twenty-three patients with a median age of 42 years (range 17-64)
      with malignancies underwent peripheral blood stem cell (PBSC) collection after
      cyclophosphamide (CY) 4 g/m2 and etoposide (600 mg/m2) followed by rhG-CSF (10
      microg/kg/day). The WBC, platelet counts, CD34+ cell counts per ml of PB, and
      CD34+ cells in apheresis products were followed in all patients. The relationship
      of the time to recovery of WBC > 1,000/microl, >3,000/microl, >10,000/microl and
      platelets >20,000/microl and 50,000/microl was compared to the average daily
      CD34+ cells/ml in each patient using the Spearman Correlation test. The tempo of
      recovery of WBC and platelets were highly correlated with the average CD34+ cell
      count in blood. In order to derive some useful guidelines for the timing of
      apheresis, the patients were divided into two groups, early recover (ER) and late
      recover (LR) based on the median time (day 10) to reach WBC count greater than
      1,000/microl. ER patients had an average daily PB CD34+ cell count of 9.04 x
      10(4)/ml (range 0.44-17.5) and a median yield of CD34+ cells of 10.43 x 10(6)/kg
      (range 0.60-25.95) compared to LR patients, who had 1.87 x 10(4)/ml (range 0.32
      5.44) in the PB (P = .001) and a yield 3.20 x 10(6)/kg CD34+ cells (range 0.037
      9.39) (P = .001). Patients recovering their WBC to 1,000/ml within 10 days of
      completing this regimen may undergo PBSC collection and achieve minimum-target
      cell doses of >2.5 x 10(6) CD34+ cells/kg--100% of the time.

PMID- 9590491
TI  - Identification of megakaryocyte precursors in peripheral blood stem cell
      collections from normal donors.
AB  - Platelet engraftment, the time course and magnitude of platelet recovery (PR)
      post-transplant, is imprecisely defined but is most often reported as the time to
      transfusion (tx) independence and/or a platelet count > or = 20,000/microl. While
      correlations between engraftment time for granulocytes (PMN) and the dose of CD34
      positive cells per kilogram are established, such associations have not been
      established for platelet engraftment. The objective of this study was to quantify
      subpopulations of CD34-positive cells in peripheral blood stem cell (PBSC)
      collections of normal, colony-stimulating factor-granulocyte) (G-CSF) primed
      donors that might represent megakaryocyte (MK) precursors, and to determine
      whether there is a statistical association between the dose transfused and the
      time course of the recovery. Based on previously published data of the sequential
      expression of CD34, HLA-DR, and CD61, among others, during MK maturation, a
      combination of corresponding antibodies for the detection of various antigen
      coexpressions by flow cytometry fluorescence-activated cell sorting [FACS] was
      chosen. CD34-positive cells were further subdivided into CD34++ (bright) and +
      (dim). Ploidy of density-gradient separated cells was examined in subsequent
      donor samples by FACS. For the entire group of patients, there was no strong
      correlation between any of the studied subpopulations and time to PR. Only in a
      selected groups of patients whose platelet counts showed a sustained increase
      during the first 6 days after engraftment, there was a weak correlation between
      the time to PR and the quantity of CD34+/+CD61+ (r = -0.57) and CD34++HLA-DR
      CD61+ (r = -0.62) cells infused. The magnitude of platelet production in these
      pt., a product of the peripheral blood platelet count and the patient's blood
      volume, was correlated with the time to PR (r = -0.73). We conclude from this
      study that subpopulations within CD34+ cells are making some contribution to PR
      in allogeneic peripheral blood stem cell transplantation, but the correlations
      are not sufficiently strong because there are probably too many unpredictable and
      unknown variables in the allogeneic setting that influence the pattern of
      engraftment.

PMID- 9590492
TI  - Cellular source of serum lactate dehydrogenase elevation in patients with
      thrombotic thrombocytopenic purpura.
AB  - Elevated serum lactate dehydrogenase (LDH) is a characteristic finding in
      patients with thrombotic thrombocytopenic purpura (TTP). It is widely accepted
      that total serum LDH principally rises due to the release of red blood cell LDH
      as a consequence of intravascular hemolysis. To identify the cellular source of
      serum LDH in TTP, we prospectively analyzed total serum LDH and LDH isoenzyme
      profiles in 10 consecutive patients with classic, acute idiopathic TTP within 5
      days of clinical presentation. Total LDH was quantitated on a Hitachi 911
      Analyzer (Indianapolis, IN), using the lactate to pyruvate reaction. LDH
      isoenzymes were measured by serum protein electrophoresis, using the Beckman LDH
      Isoenzyme Kit (Anaheim, CA). Isoenzymes attributable to erythrocytes (LDH1, LDH2)
      were not disproportionately elevated in 9 of 10 patients. LDH3 was below or
      within normal limits for all 10 patients, and one patient showed a slightly
      increased LDH4. Serum LDH5, the isoenzyme derived primarily from liver and
      skeletal muscle, was elevated 1-2 times normal in all patients. Evidence
      supporting hemolysis as the major contribution to the elevated total serum LDH
      frequently encountered in acute TTP was not identified in this study. The
      isoenzyme fractions LDH and LDH2 elevated by erythrocyte injury were not
      disproportionately elevated in this series. LDH 5, the isoenzyme found in
      skeletal muscle and liver, was consistently 1- to 2-fold greater than normal in
      all patients. We propose that the elevation of serum LDH seen in patients with
      TTP is due to release of LDH from a variety of tissues damaged as a result of
      systemic ischemia.

PMID- 9590493
TI  - Treatment of thrombotic thrombocytopenic purpura: a role for early vincristine
      administration.
AB  - Plasma exchange (PE) is considered first-line treatment for thrombotic
      thrombocytopenic purpura (TTP) to the point that many clinicians regard it as
      definitive therapy. Studies have reported response rates to PE ranging from 39%
      to 78%. In our experience, a minority of patients have been cured solely by PE.
      While adjuvant therapies (e.g., vincristine, splenectomy) have proved effective
      in anecdotal reports, protocols using these therapies in the treatment of TTP
      have not been established. Management of TTP over a 15-year period was reviewed
      to evaluate (1) the rate of cure accomplished by PE alone, and (2) the potential
      benefit of additional therapies. The records of 29 consecutive patients with TTP
      treated by PE were reviewed and classified according to response to PE alone and
      the need for adjuvant therapy. Eight patients (28%) achieved remission and long
      term survival with PE alone. With the addition of adjuvant therapy another 13
      patients survived, bringing the total survival to 72%. Fifteen patients were
      treated with vincristine in addition to PE. Only three of seven patients
      receiving vincristine after failing to respond completely to PE survived, but
      survival increased to 88% (7 of 8) when vincristine was administered within 3
      days of beginning PE. These data suggest that PE alone may not be sufficient
      therapy for most patients with TTP. Additional therapy is often needed to achieve
      long-term survival. While controlled trials will be necessary to prove the
      efficacy of vincristine, we believe that, given the minimal risk of vincristine
      toxicity and the grave consequences of ineffective therapy, routine
      administration of vincristine early in the course of PE should be considered.

PMID- 9590494
TI  - Evaluation of the gemini infusion pump for the safe delivery of peripheral blood
      progenitor cells (stem cells).
AB  - The purpose of this in vitro study was to determine whether the Gemini PC-2TX
      infusion pump could safely deliver peripheral stem cells (PSC) for an autologous
      PSC transplant. For purposes of hypothesis testing, it was assumed that there
      would be no significant difference in CD34+ cell counts and colony-forming units
      granulocyte, macrophage (CFU-GM) when the PSCs were administered by an IMED PC
      2TX infusion pump as opposed to an intravenous push method. The American Red
      Cross collected 50-ml samples of PSCs from four donors by apheresis. These cells
      were tested for CD34+ using flow cytometry and for functional progenitor cells
      using a CFU-GM assay. The cells were cryopreserved after testing. For our study,
      samples were tested simultaneously at a single facility. Each sample was
      individually thawed and a baseline thaw sample collected; 10 ml of the donor
      specimen was pushed through a syringe into a specimen container (intravenous push
      sample). The remainder of the specimen was infused through the IMED Gemini PC-2TX
      pump into a specimen container (intravenous pump sample). All samples were
      assayed for CD34+ cell counts and CFU-GM. Data analyses were conducted using the
      t-test for paired samples, with values of P < 0.05 considered significant.
      Results failed to demonstrate a statistically significant difference between the
      CD34+ or CFU-GM results of the intravenous push and intravenous pump specimens.
      Additionally, we failed to find a statistically significant difference when we
      compared the intravenous push and the intravenous pump specimens with the
      baseline thaw sample. The results of this study support the hypothesis that the
      Gemini PC-2TX infusion pump can safely deliver PSCs for the purposes of stem cell
      transplantation.

PMID- 9590495
TI  - Treatment of high-risk, refractory acquired methemoglobinemia with automated red
      blood cell exchange.
AB  - Ingestion of strong oxidant substances may result in acquired methemoglobinemia,
      a clinical condition in which the oxidized blood hemoglobin is incapable of
      delivering oxygen to the tissues, and the patient becomes cyanotic. Traditional
      first-line therapy consists of infusion of methylene blue, whose action depends
      on the availability of reduced nicotinamide adenine nucleotide phosphate (NADPH)
      within the red blood cell (RBC). Some patients, particularly those who are
      deficient in glucose-6-phosphate dehydrogenase (G6PD), will not benefit from
      methylene blue. In these patients, and in some patients who have ingested very
      strong oxidants, methylene blue may also precipitate Heinz body hemolytic anemia.
      We present a case of severe, acquired methemoglobinemia in a 26-month-old, 9.8-kg
      boy with G6PD deficiency. He was cyanotic, in respiratory failure, intubated in a
      pediatric intensive care unit. In typical fashion, he did not respond to
      methylene blue. Manual exchange of two whole blood volumes, performed over 4 1/2
      hr, also failed to resolve his severe methemoglobinemia. An automated RBC
      exchange (1.3 RBC volume), lowered his methemoglobin content from 31.8% to 7% in
      a single 40-min procedure. Thereafter his methemoglobin level continued to
      decrease rapidly and spontaneously. He was discharged home 2 days later, with
      0.4% methemoglobin. To our knowledge, this is the first report to demonstrate the
      (potentially superior) effectiveness of automated RBC exchange for treatment of
      patients with high-risk acquired methemoglobinemia, that is, those with G6PD
      deficiency or who have ingested strong oxidants.

PMID- 9590496
TI  - Therapeutic apheresis for babesiosis.
AB  - Infection with the tick-borne protozoa Babesia is becoming more common.
      Babesiosis is usually successfully treated with antibiotics but, in some cases,
      apheresis may also be indicated. We report two patients with babesiosis and
      hemolysis treated by apheresis and antibiotics. One case had traditional
      indications for red blood cell (RBC) exchange, and a second patient was treated
      with RBC exchange, and plasmapheresis for hemolysis, probably secondary to
      Babesia parasitemia. Case 1 involved a 44-year-old man with chronic relapsing
      pancreatitis who had become infected with Babesia from a unit of RBCs transfused
      during surgery. At 5 weeks after surgery, fever and severe hemolysis developed,
      along with a hemoglobin of 69 g/L; 30% of his RBCs were found to be infected with
      Babesia. This patient had several postoperative complications; the babesiosis was
      treated with clindamycin, quinine, and three RBC exchanges. Parasitemia fell to
      less then 1% of RBCs, but the patient died of pancreatitis. Case 2 was a 47-year
      old man with a renal transplant who had been receiving immunosuppressive therapy
      for 8 years. He had a history of tick bites, fever, and hemolytic anemia.
      Analysis of a peripheral blood smear detected Babesia. He was initially treated
      with antibiotic therapy and two RBC exchanges. Hemolysis improved transiently but
      worsening parasitemia developed later, as well as an IgG RBC autoantibody. He was
      then treated by plasmapheresis and RBC exchange. Although his condition improved,
      he had a third hemolytic episode, which was treated with plasmapheresis and RBC
      exchange before the parasitemia and autoimmune hemolytic anemia disappeared. In
      conclusion, immunosuppressed or severely ill people who become infected with
      Babesia may benefit from RBC exchange or plasmapheresis, or both.

PMID- 9590497
TI  - Erythroplateletapheresis with the Amicus cell separator.

PMID- 9590498
TI  - Use of flow cytometry to study growth of human airway smooth muscle cells.

PMID- 9590499
TI  - Nucleotide sequence of canine fibroblast growth factor-8 (FGF-8)

PMID- 9590500
TI  - Thyroid hormone acting on astrocytes in culture.

PMID- 9590501
TI  - Karyotypic changes associated with spontaneous acquisition and loss of
      tumorigenicity in a human transformed bronchial epithelial cell line: evidence
      for in vivo selection of transformed clones.
AB  - In this study, we describe the karyotypic changes associated with the spontaneous
      acquisition of tumorigenicity in an immortalized tumor bronchial cell line.
      Neoplastic transformation of the NL20 human bronchial epithelial cell line
      occurred after 3 yr in culture, and was associated with loss of chromosome 18
      together with acquisition of multiple copies of 9q21.2-->34. The nontumorigenic
      NL20 cell line had been established by transfection of human bronchial epithelial
      cells with the SV40 T antigen, and had retained a relatively stable karyotype
      after the first 32 passages in vitro. However, when cells from p184 were
      inoculated into nude mice, a transplantable tumor was obtained that was derived
      from a minor clone present in this otherwise stable line. Subsequent passaging of
      the NL20 cells in vitro did not yield further tumors, and the minor clone from
      which the tumorigenic NL20T cell line derived was no longer evident in NL20 cells
      by Passage 205. Furthermore, the original tumorigenic NL20T cells lost the
      neoplastic phenotype after 25 passages in vitro and reverted to the
      nontumorigenic karyotype observed at p189. In contrast to the loss of the
      tumorigenic phenotype and karyotype, which occurred with in vitro passaging of
      the original tumor, when the NL20T cells were passaged in other nude mice, they
      continued to give rise to tumors with sevenfold amplifications of 9q sequences
      and loss of chromosome 18, and cells from the secondary tumors (NL20T-A cells)
      have maintained a stable karyotype and remain tumorigenic even after 64 passages
      in vitro. A mixture of 10% tumorigenic NL20T-A and 90% nontumorigenic NL20 cells
      formed tumors in athymic nude mice when cultured in vitro on fibronectin, but not
      on plastic; cytogenetic analysis demonstrated that the tumors and cell cultures
      were composed of tumorigenic NL20T-A cells, whereas cytogenetic analysis of cells
      cultured on plastic were identical to the nontumorigenic NL20 cells. These data
      support the hypothesis that neoplastic transformation in our original cell line
      arose from in vivo selection of a small mutant clone, which had arisen in culture
      and was subsequently selected in vivo but was lost with in vitro culture.

PMID- 9590502
TI  - A novel human glassy-cell carcinoma cell line producing IL-6 and IL-8 from
      uterine cervix.
AB  - A novel human cell line, TOM-2, was established from a rare uterine cervical
      cancer, glassy cell carcinoma (GCC). TOM-2 is the second established GCC cell
      line so far reported. The cells were intermediately or poorly differentiated with
      dysplastic nuclei and polygonal shape and secreted two tumor markers and
      cytokines, i.e., CA-125 and SCC, interleukin (1L)-1alpha, -6, and -8, and TNF
      alpha. Growth of TOM-2 was so strongly dependent on population density that it
      was not possible to determine the plating efficiency. In mass culture, the
      following characteristics were observed: doubling time, 83 h; mode of chromosome
      number, 79; human papillomavirus type 18 DNA, detectable; tumorigenicity, easily
      transplantable into subcutis of nude mice; chemosensitivity in vitro,
      considerably sensitive to Cisplatin and 5-FU but not to 9 other antineoplastic
      agents. This novel cell line will be useful for developing new therapeutic
      strategies for the rare cancer, GCC.

PMID- 9590503
TI  - Hemopoiesis in long-term stroma-dependent cultures from lymphoid tissue:
      production of cells with myeloid/dendritic characteristics.
AB  - A long-term stroma-dependent culture system (LTC) has been developed which
      continuously produces hemopoietic cells providing an in vitro system for the
      study of cell differentiation. These nonadherent cell populations contain a large
      subpopulation of dendritic cells (DC). LTC producing DC were easily generated
      from spleen, but could also be established from bone marrow (BM) and lymph node
      with less success. It was difficult to establish DC-producing LTC from thymus.
      The properties of splenic and thymic stroma have been compared. Spleen stroma
      developed more complicated networks of fibroblasts, endothelial cells,
      macrophages, and DC. Thymic stromal monolayers were dominated by epithelial cells
      and fibroblasts, with a lower proportion of macrophages and endothelial cells.
      They had a relatively sparse structure of cell networks compared with spleen
      stroma. Cells with dendritiform morphology first appeared in cultures by 2-3 wk.
      The majority of cells produced were large cells which expressed DC-specific cell
      surface markers, major histocompatibility complex (MHC) Class II molecules, and
      the CD80/CD86(B7) costimulator. A high proportion of cells also expressed myeloid
      cell markers. No T or B lymphoid cells or granulocytes were present in the
      cultures. LTC continued to produce nonadherent cells resembling myeloid/DC for
      long periods, even after passage of stromal cells and stem cells at about 3-4 mo.
      after culture establishment. The LTC system offers potential to study the in
      vitro differentiation of myeloid/DC.

PMID- 9590504
TI  - A simplified method for growth of human microvascular endothelial cells results
      in decreased senescence and continued responsiveness to cytokines and growth
      factors.
AB  - Human dermal microvascular endothelial cells are used to analyze the functions of
      microvascular endothelium in vitro. However, the low yield and short lifespan of
      these cells in culture has limited the types of analysis that could be performed.
      Human microvascular endothelial cells are typically grown in media containing
      supplements such as dibutyryl cyclic AMP, hydrocortisone, bovine brain extract,
      and antifungal agents, each of which increase the complexity of experimental
      design and interpretation of results. In the present study, endothelial cells
      were transferred after Ulex europeus-I selection into a simplified medium
      consisting of Endothelial Basal Medium 131, 10% fetal bovine serum, and 2 ng/ml
      basic fibroblast growth factor and analyzed over 3 mo. The human microvascular
      endothelial cells expressed the endothelial markers von Willebrand factor, CD31,
      P-selectin, and E-selectin. In addition, the cells showed increased proliferation
      in the presence of basic fibroblast growth factor (0.5 ng/ml) or vascular
      endothelial cell growth factor (10 ng/ml). Tumor necrosis factor-alpha-induced
      expression of E-selectin was similar in cells at Passages 3, 6, and 12,
      indicating that the cells maintained responsiveness to cytokines over several
      weeks. Furthermore, the endothelial cells attained a typical cobblestone
      morphology with increased cellular density and also formed capillarylike tubes on
      Matrigel. In summary, the human dermal microvascular endothelial cells display
      the expected endothelial characteristics when grown for several passages and,
      therefore, provide a valuable in vitro model for human microvascular endothelium.

PMID- 9590505
TI  - Simulated microgravity conditions enhance differentiation of cultured PC12 cells
      towards the neuroendocrine phenotype.
AB  - We are studying microenvironmental cues which contribute to neuroendocrine organ
      assembly and tissue-specific differentiation. As our in vitro model, we cultured
      rat adrenal medullary PC12 pheochromocytoma cells in a novel cell culture system,
      the NASA rotating wall vessel (RWV) bioreactors. This "simulated microgravity"
      environment in RWV bioreactors, characterized by randomizing gravitational
      vectors and minimizing shear stress, has been shown to favor macroscopic tissue
      assembly and to induce tissue-specific differentiation. We hypothesized that the
      unique culture conditions in the RWV bioreactors might enhance the in vitro
      formation of neuroendocrine organoids. To test our hypothesis, we evaluated the
      expression of several markers of neuroendocrine differentiation in cultures of
      PC12 cells maintained for up to 20 d in the slow turning lateral vessel (STLV)
      type RWV. PC12 cell differentiation was assessed by morphological, immunological,
      biochemical and molecular techniques. PC12 cells, cultured under "simulated
      microgravity" conditions, formed macroscopic, tissue-like organoids several
      millimeters in diameter. Concomitantly, the expression of phenylethanolamine-N
      methyl transferase (PNMT), but not of other catecholamine synthesizing enzymes,
      was enhanced. Increased PNMT expression, as verified on both the gene and protein
      level, was accompanied by an increase in the specific activity of the enzyme.
      Furthermore, after 20 d in culture in the STLV, we observed altered patterns of
      protein tyrosine phosphorylation and prolonged activation of c-fos, a member of
      the AP-1 nuclear transcription factor complex. We conclude that culture
      conditions in the RWV appear to selectively activate signal transduction pathways
      leading to enhanced neuroendocrine differentiation of PC12 cells.

PMID- 9590506
TI  - Establishment and initial characterization of the ovine mammary epithelial cell
      line NISH.
AB  - Analysis of the molecular mechanisms involved in the differentiation and
      formation of the characteristic three-dimensional structures of the developing
      mammary gland of the major milk-producing livestock (ducts, end buds, and
      alveoli) requires in vitro model cell cultures. The few cell lines that have been
      established from dairy animals do not fully reproduce the entire program of
      mammary differentiation. Here we present the initial characterization of a unique
      mammary epithelial cell line derived spontaneously from midpregnant sheep (NISH).
      These cells form in vitro functional structures resembling ducts, lateral buds,
      and alveoli that secrete beta-lactoglobulin (BLG) in an ECM (extracellular
      matrix)-dependent manner. Interestingly, the presence of growth hormone
      dramatically increased BLG secretion from NISH cells cultured on ECM. It appears
      that GH is required not only to establish the structural organization but also is
      continuously needed to maintain BLG expression. Stable transfection of NISH cells
      with BLG/Human Serum Albumin (HSA) hybrid gene constructs revealed that the
      relative level of expression was comparable to the in vivo secretion of HSA in
      transgenic mice carrying these gene sequences. No expression could be detected in
      cells transfected with hybrid genes carrying either HSA cDNA or the entire HSA
      gene, and HSA expression was dependent on the presence of intronic sequences.
      These results demonstrate that NISH cells may prove a useful tool for studying
      the differentiation and organogenesis of mammary epithelial cells under defined
      culture conditions. Furthermore, transfected NISH cells may be an alternative for
      the transgenic mouse model in evaluating the potential of gene constructs to be
      efficiently expressed in the mammary gland of transgenic farm animals.

PMID- 9590507
TI  - Non-small-cell lung carcinoma cells invade human bronchial mucosa in vitro.
AB  - To study invasion of lung cancer in vitro a novel three-dimensional coculture
      assay consisting of living human tissues has been developed. Multicellular
      spheroids initiated from a new large-cell lung carcinoma cell line (GaL23), found
      to be invasive in immunodeficient mice, were confronted with precultured
      bronchial fragments derived from mucosal biopsies obtained during routine
      fiberoptic bronchoscopy. The bronchial fragments consist of a stromal core with
      scattered fibroblasts covered by a continuous surface epithelium resting on a
      basal lamina. During the first 2 wk of confrontation, a gradual retraction of the
      bronchial epithelium with subsequent adhesion of the tumor cells to the
      underlying basal lamina occurred. The following week, a limited invasion of tumor
      cells into the bronchial stroma was seen. To facilitate the entrance of tumor
      cells through the mucosal surface, the surface epithelium was removed prior to
      coculture by ethylenediaminetetraacetic acid (EDTA) buffer treatment. Upon
      confrontation, GaL23 cells then rapidly attached to and migrated on the exposed
      basal lamina and an increasing number of tumor cells was seen in the stroma
      during the first week of culture. This model offers opportunities for studying
      mechanisms of lung cancer adhesion, migration, and invasion using human bronchial
      mucosa as the natural target tissue.

PMID- 9590509
TI  - Positive regulation of normal and tumoral mammary epithelial cell proliferation
      by fibroblasts in coculture.
AB  - In the mammary gland, mesenchymal-epithelial interactions are of paramount
      importance during normal and tumoral developments. We have studied the paracrine
      growth regulation of a variety of breast epithelial cells in coculture with
      normal or pathological breast fibroblasts. Two models of coculture were used in
      which the two cell types were seeded and grown, either together in microchamber
      slides or separated by a microporous membrane. Under these two conditions, all
      fibroblasts were shown to stimulate the proliferation of the hormono-responsive
      breast carcinoma MCF-7 cell line, suggesting that cell contacts were not
      indispensable for the paracrine stimulation of MCF-7 cell growth by fibroblasts.
      Moreover, in the Transwell coculture system, the proliferation of a variety of
      other breast carcinoma cells (MDA-MB231, T47D, and BT-20) was also stimulated by
      fibroblasts. However, the amplitude of the proliferative response seemed to be
      dependent on the carcinoma cell line considered. Moreover, the proliferative
      response of normal mammary epithelial cells to the presence of fibroblasts was
      shown to be significantly higher than the tumor cell response. The nature of the
      tissue of fibroblast origin, normal or pathological, did not influence the growth
      response of the epithelial cells. In this study, we thus demonstrate that
      fibroblasts are able to stimulate the proliferation of normal and carcinoma cells
      through paracrine exchange mechanisms. We also conclude that the target
      epithelial cell phenotype will essentially determine the extent of the
      proliferative response.

PMID- 9590508
TI  - Basic fibroblast growth factor regulates extracellular matrix and contractile
      protein expression independent of proliferation in vascular smooth muscle cells.
AB  - Basic fibroblast growth factor (bFGF) can influence proliferation and
      differentiation in vascular smooth muscle cells. Basic FGF promotes some features
      of the synthetic phenotype (proliferation) but is known to inhibit others
      (collagen synthesis). Whether bFGF availability influences smooth muscle cell
      phenotype independent of proliferation is not known. The purpose of this study
      was to determine if the effects of bFGF on extracellular matrix and contractile
      protein expression are dependent on changes in proliferation. Basic FGF
      availability was manipulated by adding bFGF to cultured cells or by inhibiting
      bFGF expression using antisense RNA, and adjusting culture conditions such that
      proliferation was held constant. Compared to cells cultured in serum alone,
      smooth muscle alpha-actin and myosin heavy chain expression was markedly reduced
      by added bFGF, but was not influenced by antisense inhibition of bFGF expression.
      Under the same conditions, collagen synthesis was inhibited by added bFGF, and
      was stimulated by reduced bFGF expression. These consequences of altering bFGF
      availability were not associated with changes in FGF receptor expression. These
      findings demonstrate that alterations in bFGF availability can regulate smooth
      muscle cell phenotype independent of proliferation, which may be related to the
      regulation of smooth muscle cell phenotype in vivo.

PMID- 9590510
TI  - Stimulation of tyrosylprotein sulfotransferase activity by ethanol: role of
      increased enzyme level.
AB  - Tyrosylprotein sulfotransferase (TPST), an enzyme involved in the
      posttranslational modification of proteins, plays important role in the
      biological activity and secretion of proteins. Previously we have shown an
      increased activity of this enzyme in gastric mucosa of alcoholics. In the present
      study, effect of ethanol on TPST was examined in rat liver and gastric mucosa
      utilizing enzyme assays and Western blot analyses for TPST levels. Male Sprague
      Dawley rats were pair-fed Leiber-DeCarli liquid diets for 10 days and controls
      received a liquid diet in which dextrose was isocalorically substituted for
      ethanol. After ethanol feeding, rats were sacrificed and liver and gastric mucosa
      were processed for Golgi membrane preparation. The TPST activity was measured
      using poly(Glu6, Ala3, Tyr1) as the sulfate acceptor and PAPS as sulfate donor.
      There was a threefold increase in TPST activity of gastric mucosa of animals
      subjected to chronic alcohol feeding. In the liver, the increase in tyrosine
      sulfating activity was also around threefold. The kinetic studies performed to
      understand the mechanism involved in ethanol stimulation of TPST activity showed
      no change in the Km values of the enzyme by ethanol. In control and ethanol
      treated animals, the Km for EAY was 0.41-0.53 and 0.43-0.53 microM, and the Km
      for PAPS was 10-12.5 and 9-17 microM, respectively. The Vmax in ethanol-fed
      animals was increased by 1.5- to 2-fold. The increase in TPST activity in
      experimental rats was further tested by analyzing the Western blots by Imaging
      Densitometer for TPST levels. Analysis of TPST levels also showed over threefold
      increase in the stomach and liver of ethanol-fed rats. Our results indicate that
      stimulation of TPST by ethanol involves increased TPST level rather than change
      in affinity for its substrates.

PMID- 9590511
TI  - Ethanol inhibition of phagocytosis and superoxide anion production by microglia.
AB  - Ethanol consumption has been associated with aberrant immune responses resulting
      in increased susceptibility to infection including opportunistic infections of
      the central nervous system. We have investigated the effects of chronic ethanol
      treatment on phagocytosis and production of superoxide anion by microglia.
      Phagocytosis of radio-labeled opsonized E. coli was markedly suppressed by
      treating microglia with ethanol. The unstimulated synthesis of superoxide anion
      was not altered by ethanol treatment of microglia, but ethanol treatment
      effectively suppressed phorbol-12 myristate-13 acetate-stimulated microglia
      superoxide anion production. The results indicate that ethanol inhibition of
      microglia function may play a role in increased susceptibility for central
      nervous system infections, particularly in immunocompromised subjects.

PMID- 9590512
TI  - A comparison of the effects of the opioid antagonists naltrexone, naltrindole,
      and beta-funaltrexamine on ethanol consumption in the rat.
AB  - The effects of the universal opioid antagonist naltrexone were compared to the
      delta-selective opioid antagonist naltrindole and the mu-selective opioid
      antagonist beta-funaltrexamine on ethanol consumption in the absence of food or
      fluid deprivation using a limited access procedure in Wistar rats. Both
      naltrexone, at doses of 0.1, 0.25, 0.5, 1.0, 3.0, and 10 mg/kg, and beta
      funaltrexamine, at doses of 5.0 and 20.0 mg/kg, significantly decreased
      consumption of a 6% ethanol solution compared to saline control groups.
      Naltrindole, at doses of 5.0 and 15.0 mg/kg, failed to significantly reduce
      ethanol consumption. In addition, the highest doses of naltrexone, which
      antagonize delta as well as mu-opioid receptors, did not differ significantly
      from the lowest doses in their ability to reduce ethanol consumption. These data
      suggest that ethanol consumption using the limited access paradigm in the outbred
      rat is modulated by mu rather than delta-opioid receptors. Although this is not
      consistent with other data showing that delta antagonists decrease ethanol
      consumption, it is suggested that these difference may be related to the alcohol
      preferring rats used in those experiments.

PMID- 9590514
TI  - Ethanol enhances cholesterol synthesis and secretion in human hepatomal cells.
AB  - Excessive consumption of alcohol leads to severe alterations of lipid metabolism,
      including hyperlipemia and hypercholesterolemia. Following these epidemiological
      observations, we investigated the effects of ethanol at the cellular level by
      employing a human hepatomal cell line (HepG2) and by evaluating the biosyntheses
      of lipid classes from different labeled precursors. Incubation of cells with 2%
      ethanol resulted in a decreased labeling of phospholipids and in an increase in
      cholesterol synthesis and secretion. Triglyceride synthesis was increased by
      ethanol but their secretion in the medium was reduced, suggesting that these
      alterations may be related to their accumulation in the liver. The alcohol
      induced alterations of lipid metabolism are not due to its metabolite
      acetaldehyde and data suggest that alcohol enhances cholesterol synthesis by
      affecting the initial steps without increasing HMGCoA expression. The observed
      modifications of lipid metabolism in HepG2 may partially explain the enhanced
      incidence of cardiovascular disorders that has been associated with alcoholism.

PMID- 9590513
TI  - Serotonin3 receptor antagonism of alcohol intake: effects of drinking conditions.
AB  - The effects of 5-HT3 receptor antagonists on ethanol intake were examined in the
      selectively bred alcohol-preferring P line of rats under continuous and limited
      access to 10% (v/v) ethanol with food and water ad lib. Single daily injections
      of either MDL 72222 (MDL) or ICS 205-930 (ICS) (0.01-3.0 mg/kg, SC) given 60 min
      before a 4-h scheduled access period for 4 consecutive days failed at all doses
      to alter the intake of a 10% (v/v) ethanol solution by P rats. However, multiple
      daily injections of either MDL (1-3 mg/kg, SC) or ICS (3.0 and 5.0 mg/kg, SC),
      given three times daily at 4-h intervals, significantly reduced ethanol intake
      under 24-h free-choice conditions on the first treatment day. Additionally, a
      single administration of 1.0 mg/kg MDL reduced 24-h free-choice ethanol intake by
      approximately 50% of control values and had no effect on 24-h saccharin intake.
      The effects of MDL were further examined in a 2-h schedule access paradigm in
      which rats received the access period at the same time every day (Fixed) or
      randomly during the dark cycle (Variable). Although 1.0 mg/kg MDL had little
      effect on ethanol drinking in the Fixed group, ethanol intake was reduced by 55%
      of control levels in the Variable group. Overall, the data indicate that drinking
      conditions influence the effectiveness of 5-HT3 antagonists to reduce ethanol
      consumption. Furthermore, the results suggest that conditions, associated with
      limited access ethanol drinking, markedly reduce the actions of 5-HT3 antagonists
      on ethanol intake.

PMID- 9590515
TI  - The effect of ethanol and its metabolites upon methionine synthase activity in
      vitro.
AB  - The association of alcoholism with macrocytic anaemia has lead to investigation
      of the role of cobalamin-dependent methionine synthase in mediating alcohol
      toxicity. Several studies have found that long-term ingestion of large quantities
      of ethanol causes inhibition of liver methionine synthase activity in vivo:
      however, ethanol has not been found to inhibit the enzyme directly. The effect of
      ethanol and its breakdown products, acetate and acetaldehyde, on highly purified
      rat liver methionine synthase was tested in vitro. Enzyme activity was not
      inhibited by ethanol or acetate. Acetaldehyde was found to inhibit methionine
      synthase activity, with an apparent IC50 of 2 mM. The reported inhibition by
      acetaldehyde was found to become irreversible over time. Acetaldehyde-induced
      inhibition of liver methionine synthase activity is thus proposed as the most
      likely explanation of the reported in vivo effect of ethanol upon methionine
      synthase.

PMID- 9590517
TI  - Ethanol-induced hypothermia and thermogenesis of brown adipose tissue in the rat.
AB  - The effects of two ethanol doses (2 and 3 g/kg) on colonic temperature and levels
      of norepinephrine (NE) and uncoupling protein (UCP) mRNA in the interscapular
      brown adipose tissue (IBAT) were examined in rats exposed to 20 degrees C or 4
      degrees C for 2 h. The controls received 0.9% NaCl solution. Ethanol produced a
      significant hypothermic effect versus saline at both temperature conditions. The
      dose at 3 g/kg reduced colonic temperature more in the cold than at room
      temperature (p < 0.01), whereas the ambient temperature did not affect the
      decrease in rats that received ethanol 2 g/kg. At room temperature ethanol did
      not significantly change the levels of NE or UCP mRNA, whereas after cold
      exposure (4 degrees C) NE levels in the ethanol-treated rats were significantly
      lower than in the controls (p < 0.001). Ethanol did not prevent a cold-induced
      increase in the UCP mRNA levels, although it reduced an increase. The magnitude
      of the reduction in increase was dependent on the dose, being significant at the
      dose of 3 g/kg (p < 0.05). The results show that the ethanol-induced drop in body
      temperature is not necessarily related to IBAT thermogenesis, as indicated by the
      levels of NE and UCP mRNA.

PMID- 9590516
TI  - Developmental differences in the acquisition of tolerance to ethanol.
AB  - This study was designed to compare the development of tolerance to ethanol in
      adolescent and adult rats. Rats were pretreated with ethanol (4 g/kg) twice daily
      by intragastric gavage for 3 or 7 days, and then challenged with a single IP dose
      of ethanol (5 g/kg). Throughout the pretreatment period body temperature was
      measured before and after the morning dosage. During the IP challenge test we
      measured body temperature, duration of the loss of righting reflex, and blood
      ethanol level upon regaining the righting reflex. The adolescent rats that were
      pretreated for 7 days developed greater tolerance to the effects of ethanol on
      body temperature during the pretreatment period. No tolerance was observed in
      animals that received only 3 days of pretreatment. Ethanol decreased body
      temperature to a greater extent in adolescent animals than adults in response to
      the IP challenge dose, but there was no significant difference between control
      and pretreated animals in either age group. The time to regain the righting
      reflex was lower in adolescent rats than in adults. Post hoc analyses indicated
      that 7 days of ethanol pretreatment diminished the effects of the IP ethanol
      challenge on the loss of righting reflex in adolescent but not adult rats.
      Although adolescent rats regained the righting reflex with higher blood ethanol
      levels than adults, there was no significant effect of ethanol pretreatment on
      that measure. These findings indicate that the development of tolerance to the
      temperature regulatory effects of ethanol is more marked in the adolescent rat
      than in the adult. This developmental difference in ethanol sensitivity is
      consistent with other recent findings and suggests that adolescence may be a
      period of unique sensitivity to a number of the behavioral and physiological
      effects of ethanol.

PMID- 9590518
TI  - Arterio-venous ethanol levels in blood and plasma after intravenous injection in
      rabbits.
AB  - Arterio-venous ethanol concentrations in both whole blood and plasma were
      determined as a function of time in the rabbit. Following i.v. injection of 1.0
      g/kg, both arterial and venous ethanol concentrations showed an abrupt decline
      occurring immediately after the end of the administration, followed by a
      pseudolinear phase that persisted for the length of the experiment. This work
      substantiates the arterio-venous ethanol concentration differences reported in
      the literature. It illustrates that equal arterial and venous ethanol
      concentrations may not be achieved readily after rapid i.v. injection. Moreover,
      it demonstrates a faster decay of ethanol concentrations in arterial than in
      venous plasma.

PMID- 9590519
TI  - Effects of prenatal alcohol and pair feeding on lipopolysaccharide-induced
      secretion of TNF-alpha and corticosterone.
AB  - Fetal alcohol exposure (FAE) produces profound alterations in immunological and
      neuroendocrine functions. The present study examined the effects of FAE on the
      secretion of tumor necrosis factor (TNF-alpha) and corticosterone following
      administration of lipopolysaccharide (LPS) in normal (N) adult rats, in adult
      offspring of dams fed a liquid diet supplemented with ethanol (E), and in pair
      fed control offspring (P). LPS-induced TNF-alpha secretion was not affected by
      either gender or prenatal treatment. In contrast, LPS-induced corticosterone
      secretion was significantly greater in female than in male rats, and at 60-min
      post-LPS was significantly higher in E and P, compared to N females. Ovariectomy
      significantly inhibited LPS-induced TNF-alpha secretion in E, but not in P and N,
      rats and chronic replacement with 17-beta-estradiol markedly inhibited TNF-alpha
      secretion in ovariectomized E and N, but not in P, rats. In contrast, ovariectomy
      reduced the effects of LPS on corticosterone secretion in all groups, and chronic
      replacement with 17-beta-estradiol reversed this effect. These findings indicate
      that LPS-induced secretion of corticosterone, but not TNF-alpha, is affected by
      prenatal manipulations and by gender. In addition, alterations in the hormonal
      environment in females modulate LPS-induced corticosterone secretion in all
      prenatal treatment groups, but differentially influence TNF-alpha secretion in
      rats exposed to alcohol, restricted feeding, or normal diets in utero.

PMID- 9590520
TI  - Behavioral detection of low concentrations of ethanol in milk in the preweanling
      rat.
AB  - Previous animal models testing infantile reactivity to ethanol (EtOH) in maternal
      milk used EtOH doses that vastly exceeded levels actually encountered in a mildly
      or moderately intoxicated dam. The present study assessed whether 12- and 16-day
      old rats are capable of detecting EtOH in milk at levels actually recorded in an
      intoxicated dam. Experiment 1 determined representative levels of EtOH in
      maternal milk as a function of maternal intragastric administration of EtOH (0.5
      3.0 g/kg). Experiment 2A assessed generalization of conditioned taste aversions
      accrued with a high level of EtOH (6%) in either water or milk vehicles towards
      lower, more representative EtOH levels obtained from Experiment 1. With body
      weight gain as the dependent measure, conditioned aversions to milk were evident
      with the milk vehicle, but there was no detection of EtOH at any level at either
      age. Detection of the high level of EtOH (6%) in milk, however, was observed by
      16 day olds within an habituation paradigm (Exp. 2b) via cardiac and behavioral
      (locomotion, mouthing) indexes. In Experiment 3 application of Experiment 2's
      more sensitive, behavioral index to assess generalization of the conditioned
      taste aversions revealed detection of a lower, more representative concentration
      of EtOH (175 mg%) in milk in 16-day-old rats. Overall the results show that the
      unweaned rat is capable of detecting very low concentrations of EtOH in milk and
      can modify their behavior accordingly. The expression of this capability is not,
      however, homogeneous across different response indexes. In conjunction with prior
      research it is clear that the infant rat's perception of EtOH in milk, including
      the very low levels of EtOH found in maternal milk during mild or moderate
      intoxication, is a relevant experience for generating new responses towards EtOH.

PMID- 9590521
TI  - Stable carbon and oxygen isotopes in human tooth enamel: identifying
      breastfeeding and weaning in prehistory.
AB  - This paper investigates the utility of stable carbon and oxygen isotopes in human
      dental enamel to reveal patterns of breastfeeding and weaning in prehistory.
      Enamel preserves a record of childhood diet that can be studied in adult
      skeletons. Comparing different teeth, we used delta13C to document the
      introduction of solid foods to infant diets and delta18O to monitor the decline
      of breastfeeding. We report enamel carbonate delta13C and delta18O of 33 first
      molars, 35 premolars, and 25 third molars from 35 burials from Kaminaljuyu, an
      early state in the valley of Guatemala. The skeletons span from Middle Preclassic
      through Late Postclassic occupations, ca. 700 B.C. to 1500 A.D. Sections of
      enamel were removed from each tooth spanning from the cusp to the cemento-enamel
      junction. Stable isotope ratios were measured on CO2 liberated by reaction of
      enamel with H3PO4 in an automated carbonate system attached to a VG Optima mass
      spectrometer. Within a skeleton, teeth developing at older ages are more enriched
      in 13C and more depleted in 18O than teeth developing at younger ages. Premolars
      average 0.5/1000 [corrected] higher in delta13C than first molars from the same
      skeleton (P = 0.0001), but third molars are not significantly enriched over
      premolars. The shift from first molars to premolars may be due to the shift to
      solid foods from lipid-rich milk. After 2 years, when premolars begin to
      mineralize, the delta13C in childhood diets did not change systematically. First
      molars and premolars are similar in delta18O, but third molars average 0.7/1000
      [corrected] lower than first molars (P = 0.0001) and 0.5/1000 [corrected] lower
      than premolars (P = 0.0003). First molar and premolar delta18O is heavier,
      because breast milk is more enriched in 18O than is drinking water. Hence, many
      children continued to nurse during the period of premolar formation. Together,
      these results indicate that Kaminaljuyu children had begun to eat solid maize
      foods before the age of 2 years but continued to drink breast milk until much
      later.

PMID- 9590522
TI  - Intrapopulational body size variation and cranial capacity variation in Middle
      Pleistocene humans: the Sima de los Huesos sample (Sierra de Atapuerca, Spain).
AB  - A sexual dimorphism more marked than in living humans has been claimed for
      European Middle Pleistocene humans, Neandertals and prehistoric modern humans. In
      this paper, body size and cranial capacity variation are studied in the Sima de
      los Huesos Middle Pleistocene sample. This is the largest sample of non-modern
      humans found to date from one single site, and with all skeletal elements
      represented. Since the techniques available to estimate the degree of sexual
      dimorphism in small palaeontological samples are all unsatisfactory, we have used
      the bootstraping method to asses the magnitude of the variation in the Sima de
      los Huesos sample compared to modern human intrapopulational variation. We
      analyze size variation without attempting to sex the specimens a priori.
      Anatomical regions investigated are scapular glenoid fossa; acetabulum; humeral
      proximal and distal epiphyses; ulnar proximal epiphysis; radial neck; proximal
      femur; humeral, femoral, ulnar and tibial shaft; lumbosacral joint; patella;
      calcaneum; and talar trochlea. In the Sima de los Huesos sample only the humeral
      midshaft perimeter shows an unusual high variation (only when it is expressed by
      the maximum ratio, not by the coefficient of variation). In spite of that the
      cranial capacity range at Sima de los Huesos almost spans the rest of the
      European and African Middle Pleistocene range. The maximum ratio is in the
      central part of the distribution of modern human samples. Thus, the hypothesis of
      a greater sexual dimorphism in Middle Pleistocene populations than in modern
      populations is not supported by either cranial or postcranial evidence from Sima
      de los Huesos.

PMID- 9590523
TI  - The instantaneous center of rotation during human jaw opening and its
      significance in interpreting the functional meaning of condylar translation.
AB  - Mandibular condyles translate back and forth during mouth closing and opening in
      primates and most other mammals. To account for the functional significance of
      this phenomenon, several hypotheses have been proposed. The sarcomere-length
      hypothesis holds that condylar translation provides a mechanical advantage by
      minimizing sarcomere-length changes in the masseter-medial pterygoid complex
      throughout a wide range of jaw openings. As the hypothesis is inherently
      associated with the locations of the instantaneous centers of rotation (ICRs) of
      the mandible, a more accurate determination of this variable would help test this
      hypothesis. This study investigated ICRs in the sagittal plane during human
      symmetrical mandibular opening based on a recently developed analytical method.
      The results confirmed that, with inter- and intraindividual variation, the
      natural opening was a simultaneous rotational and translational motion. In
      addition, the ICR was found to lie closer to the condyle during the first 10
      degrees than during the rest of the rotation. This suggests that for the condyles
      the rotational component is somewhat more significant at the early phase than at
      the late phase of the opening stroke. For the whole range of the natural opening,
      the grossly approximated centers of rotation (CRs) scattered below the palpable
      lateral condylar poles in the superior half of the ramus. This study supports
      neither the ICR path determined by Grant ([1973], J. Biomech. 6:109-113) nor the
      conclusions reached by recording manually operated jaw movements in human
      cadavers (Rees [1954] Br. Dent. J. 6:125-133). Moss's suggestion ([1960]
      Disorders of the Temporomandibular Joint (Philadelphia: W.B. Saunders), pp. 73
      88) that the center of rotation lies at the lingula is also not confirmed.
      Although the new data cannot reject the sarcomere-length hypothesis, they do not
      strongly support it either. Another hypothesis is proposed in this study as
      plausible. With this hypothesis, translation is regarded as an adaptation to the
      use of the inferior head of the lateral pterygoid as a jaw depressor in
      noncarnivorous mammals. Potential functional advantages of this portion of the
      muscle are also discussed.

PMID- 9590524
TI  - Clues to recognition of fungal origin of lytic skeletal lesions.
AB  - The present study addresses the specificity of lytic osseous impact for
      distinguishing among metastatic cancer, tuberculosis, and fungal disease. Osseous
      impact is used in this manuscript as a convention to describe the macroscopic
      appearance of defleshed bones affected by the disease. Osseous changes in the
      skeleton of a 47-year-old black male, diagnosed in life as having blastomycosis,
      were characterized and compared to lytic lesions observed in ten individuals with
      tuberculosis and six with metastatic cancer in the Terry and Hamman-Todd
      Collections. Apparent distinguishing characteristics are identified. Eroded
      areas, present as fronts of resorption or the result of space-occupying masses in
      blastomycosis, with protruding, short, blunt, 1 x 2 mm spicules of new bone, are
      surrounded by periosteal reaction. These differed from smooth zones of resorption
      and coalesced lesions, with a smoothed marginal zone and space-occupied
      appearance--bone-displacing mass--in tuberculosis and lytic (nonpermeative)
      lesions of metastatic cancer. Displacing is a convention (an artificial term)
      denoting bone resorption and reformation at the outer edge of the tumor mass,
      giving the impression that the surrounding bone had expanded beyond its original
      margins. Irregular trabeculae are occasionally preserved in the margins, but
      remodeling in the form of blunting of those trabeculae is not observed
      macroscopically in either tuberculosis or metastatic cancer. Two apparently
      specific lesion types are noted in blastomycosis. Periosteal reaction surrounding
      fronts of resorption appears specific, at least for nonarticular osseous lytic
      lesions, among the three entities studied. Remodeling of isolated internal
      trabeculae in the space-occupying mass lesions of blastomycosis also appears
      unique among the three disorders studied. Comparison with coccidioidomycosis
      suggests that extrapolation of blastomycosis findings to other fungal diseases is
      feasible; description of additional clinically diagnosed cases is awaited.

PMID- 9590525
TI  - Evidence from facial morphology for similarity of Asian and African
      representatives of Homo erectus.
AB  - It has been argued that Homo erectus is a species confined to Asia. Specialized
      characters displayed by the Indonesian and Chinese skulls are said to be absent
      in material from eastern Africa, and individuals from Koobi Fora and Nariokotome
      are now referred by some workers to H. ergaster. This second species is held to
      be the ancestor from which later human populations are derived. The claim for two
      taxa is evaluated here with special reference to the facial skeleton. Asian
      fossils examined include Sangiran 4 and Sangiran 17, several of the Ngandong
      crania, Gongwangling, and of course the material from Zhoukoudian described by
      Weidenreich ([1943] Palaeontol. Sin. [New Ser. D] 10:1-484). African specimens
      compared are KNM-ER 3733 and KNM-ER 3883 from Koobi Fora and KNM-WT 15000 from
      Nariokotome. Hominid 9 from Olduvai is useful only insofar as the brows and
      interorbital pillar are preserved. Neither detailed anatomical comparisons nor
      measurements bring to light any consistent patterns in facial morphology which
      set the African hominids apart from Asian H. erectus. Faces of the African
      individuals do tend to be high and less broad across the orbits. Both of the
      Koobi Fora crania but not KNM-WT 15000 have nasal bones that are narrow
      superiorly, while the piriform aperture is relatively wide. In many other
      characters, including contour of the supraorbital torus, glabellar prominence,
      nasal bridge dimensions, internasal keeling, anatomy of the nasal sill and floor,
      development of the canine jugum, orientation of the zygomaticoalveolar pillar,
      rounding of the anterolateral surface of the cheek, formation of a malar
      tubercle, and palatal rugosity, there is variation among individuals from
      localities within the major geographic provinces. Here it is not possible to
      identify features that are unique to either the Asian or African assemblages.
      Additional traits such as a forward sloping "crista nasalis," presence of a
      "sulcus maxillaris," a high (and massive) cheek coupled with some flexion of the
      malar pillar, and a posterior position for the incisive canal are present in all
      groups. These characters seem to be plesiomorphic, in comparison to the derived
      states evolved in later humans. Much or all of the variation in facial form can
      be attributed to sex dimorphism and/or local differentiation of populations
      within the Asian and African geographic regions. Metric differences among the
      fossils are comparable to those documented in a subset of recent H. sapiens, and
      there is no evidence that the Pleistocene specimens show greater dispersion than
      expected within a single species. This finding is generally in keeping with
      observations made on other parts of the cranium, lower jaw, and teeth. All of the
      hominids can be placed in H. erectus. Although its phylogenetic origins remain
      obscure, this lineage must be rooted in Africa. The species flourished for a long
      time. At several sites in China, H. erectus is known from deposits of the later
      Middle Pleistocene, while at Ngandong in Indonesia, archaic people may have
      survived even into the Late Pleistocene (Swisher et al. [1996] Science 274:1870
      1874). The Ngandong fossils may record the last appearance of the lineage.

PMID- 9590526
TI  - Patterns of strain in the macaque ulna during functional activity.
AB  - In vivo bone strain experiments were performed on the ulnae of three female
      rhesus macaques to test how the bone deforms during locomotion. The null
      hypothesis was that, in an animal moving its limbs predominantly in sagittal
      planes, the ulna experiences anteroposterior bending. Three rosette strain gauges
      were attached around the circumference of the bone slightly distal to midshaft.
      They permit a complete characterization of the ulna's loading environment.
      Strains were recorded during walking and galloping activities. Principal strains
      and strain directions relative to the long axis of the bone were calculated for
      each gauge site. In all three animals, the lateral cortex experienced higher
      tensile than compressive principal strains during the stance phase of walking.
      Compressive strains predominated at the medial cortex of two animals (the gauge
      on this cortex of the third animal did not function). The posterior cortex was
      subject to lower strains; the nature of the strain was highly dependent on
      precise gauge position. The greater principal strains were aligned closely with
      the long axis of the bone in two animals, whereas they deviated up to 45 degrees
      from the long axis in the third animal. A gait change from walk to gallop was
      recorded for one animal. It was not accompanied by an incremental change in
      strain magnitudes. Strains are at the low end of the range of strain magnitudes
      recorded for walking gaits of nonprimate mammals. The measured distribution of
      strains in the rhesus monkey ulna indicates that mediolateral bending, rather
      than anteroposterior bending, is the predominant loading regime, with the neutral
      axis of bending running from anterior and slightly medial to posterior and
      slightly lateral. A variable degree of torsion was superimposed over this bending
      regime. Ulnar mediolateral bending is apparently caused by a ground reaction
      force vector that passes medial to the forearm. The macaque ulna is not
      reinforced in the plane of bending. The lack of buttressing in the loaded plane
      and the somewhat counterintuitive bending direction recommend caution with regard
      to conventional interpretations of long bone cross-sectional geometry.

PMID- 9590527
TI  - Localization of prolyl endopeptidase mRNA in small growing follicles of porcine
      ovary.
AB  - Prolyl endopeptidase (EC3.4.21.26) has been considered a unique intracellular
      enzyme catalyzing internal peptide bond hydrolysis of Pro-X. In this study, the
      distribution of prolyl endopeptidase activity and its mRNA was investigated in
      the follicles of porcine ovary. Both follicular fluid and granulosa cell
      fractions from small follicles showed higher activity than those from large
      follicles. Molecular cloning and Northern blot analysis suggested that only one
      species of prolyl endopeptidase gene was expressed in the ovary. In addition, in
      situ hybridization study revealed that the prolyl endopeptidase mRNA expression
      was more noticeable in the granulosa cell layers of small ovarian follicles than
      in those of large follicles, suggesting its importance in the early stage of
      follicular development.

PMID- 9590528
TI  - In vitro and in vivo study of pluripotency in intraspecific hybrid cells obtained
      by fusion of murine embryonic stem cells with splenocytes.
AB  - Hypoxanthine phosphoribosyltransferase-deficient (HPRT-) mouse embryonic stem
      (ES) cells, HM-1 cells (genotype XY), were fused with adult female DD/c mouse
      spleen cells. As a result, a set of HAT-resistant clones was isolated. Four
      hybrid clones most similar in morphology and growth characteristics to the HM-1
      cells were studied in detail with respect to their pluripotency. Of these, three
      clones contained 41-43 chromosomes, and one clone was nearly tetraploid. All the
      clones had the XXY set of sex chromosomes and expressed the HPRT of the somatic
      partner only. The hybrid clones shared features with the HM-1 cells, indicating
      that they retained their pluripotent properties: (1) embryonic ECMA-7 antigen,
      not TROMA-1 antigen, was present in most cells; (2) the hybrid cells showed high
      activity of endogenous alkaline phosphatase (AP); (3) all the hybrid clones were
      able to form complex embryoid bodies containing derivatives of all the embryonic
      germinal layers; (4) the hybrid cells contained synchronously replicating X
      chromosomes, indicating that they were in an active state; and (5) a set of
      chimeric animals was generated by injecting hybrid cells into BALB/c and C57BL/6J
      mouse blastocysts. Evidence for chimerism was provided by the spotted coat
      derived from 129/Ola mice and identification of 129/Ola glucose phosphate
      isomerase (GPI) in many organs. Thus the results obtained demonstrated that the
      hybrid cells retain their high pluripotency level despite the close contact of
      the "pluripotent" HM-1 genome with the "somatic" spleen cell genome during hybrid
      cell formation and the presence of the "somatic" X chromosome during many cell
      generations. The presence of HPRT of the somatic partner in many organs and
      tissues, including the testes in chimeric animals, shows that the "somatic" X
      chromosome segregates weakly, if at all, during development of the chimeras.
      There were no individuals with the 129/Ola genotype among the more than 50
      offspring from chimeric mice. The lack of the 129/Ola genotype is explained by
      the imbalance of the sex chromosomes in the hybrid cells rendering the passage of
      hybrid cell descendants through meiosis in chimeras impossible. As a result,
      chimeras become unable to produce gametes of the hybrid cell genotype.

PMID- 9590529
TI  - Total protein content and protein synthesis within pre-elongation stage bovine
      embryos.
AB  - Protein content was measured in zona-free bovine oocytes and pre-elongation stage
      embryos, following in vitro maturation, fertilisation, and then culture in
      Synthetic Oviduct Fluid medium supplemented with amino acids and 8 mg ml(-1)
      bovine serum albumin (BSA). Values (ng embryo(-1)) of 122 +/- 7.8, 137 +/- 8.6,
      111 +/- 8.8, 115 +/- 10.4, 139 +/- 9.0 and 152 +/- 10.1 were obtained for zona
      free mature oocytes, 2-cell (day 2), 8-cell (day 3), compact morula (day 6),
      blastocyst (day 7), and expanded blastocyst (day 8) stage embryos, respectively.
      The protein content of day 7 zona-enclosed blastocysts was 337 +/- 58.0 ng
      embryo(-1). These values suggest that prior to compaction and blastulation, the
      early cleavage stage bovine embryo has a higher rate of protein degradation than
      that of synthesis. Net growth is observed only after initiation of compaction.
      The protein content of day 7 blastocysts was measured in embryos following in
      vitro production and culture in the same media supplemented with either 0.5% w/v
      polyvinyl alcohol (PVA), 8 mg ml(-1) BSA, 8 mg ml(-1) BSA and further
      supplemented with 10% fetal calf serum (FCS) from the beginning of culture (FCS
      D1), 8 mg ml(-1) BSA and 10% FCS from the fourth day of culture (day 5 of
      development) or from in vivo-derived day 7 blastocysts. Protein content was
      significantly (P < 0.05) lower in PVA-cultured embryos than other treatments. To
      determine if this difference in PVA-cultured embryos was due to a difference in
      the rate of protein synthesis, comparisons were made between day 7 embryos
      derived from BSA-culture and either PVA-culture, FCS-D1 culture or in vivo
      derived embryos. Despite differences in diameter, no significant difference was
      observed in the incorporation of L-[2,3,4,5,6-3H]-phenylalanine into the TCA
      precipitable fraction in any of the three comparisons made. However, incubation
      in the presence of FITC-abelled BSA or beta-casein and examination under either
      fluorescence or confocal microscopy revealed that protein in the extra-embryonic
      environment was actively taken up by the trophectoderm of day 7 blastocysts, most
      likely by endocytosis. These results suggest that exogenous protein is an
      important nutritive source, probably maintaining intracellular amino acid pools.
      Results obtained from the production of em bryos in protein-free medium should be
      viewed with the knowledge that such embryos differ metabolically from those
      embryos grown in the presence of protein, including in vivo-derived embryos.

PMID- 9590530
TI  - Contributions of Na+/H+ exchanger isoforms to preimplantation development of the
      mouse.
AB  - Previous work provided evidence of Na+/H+ exchanger activity in the apical domain
      of mouse trophectodermal plasma membranes that provides a route for entry of
      extracellular Na+ (Manejwala et al., 1989). This activity was hypothesized to
      contribute to the trans-trophectodermal Na+ flux that is required for blastocoel
      expansion. In the present work, we have used reverse transcriptase-polymerase
      chain reaction (RT-PCR) and immunocytochemistry to identify members of the Na+/H+
      exchanger (NHE) family that are likely to participate in this process. When cDNA
      preparations from ovulated oocytes and several stages of preimplantation
      development were tested with PCR primers specific for the NHE-1, -2, -3, and -4
      isoforms of the exchanger, only amplicons representing the NHE-1 and NHE-3
      isoforms were detected. The identity of these amplicons was confirmed by direct
      sequencing. NHE-1 mRNA is present in oocytes and in all preimplantation stages,
      increasing threefold on a per embryo basis between the 4-cell and blastocyst
      stages. NHE-3 mRNA, on the other hand, was only detected in oocytes.
      Immunocytochemical analysis of blastocysts revealed that NHE-1 is localized in
      the basolateral domain of the trophectoderm, whereas NHE-3 is localized in the
      apical domain, a situation like that in epithelia of adult organs. We conclude
      that NHE-3, an oogenetic product that persists into the blastocyst stage, is the
      Na+/H+ exchanger isoform most likely to be involved in blastocoel expansion.

PMID- 9590531
TI  - In vitro and early in vivo development of sheep gynogenones and putative
      androgenones.
AB  - Genomic imprinting, where only one of the two parental genes is expressed, occurs
      in many phyla. In mammals, however, this phenomenon has been primarily studied in
      mice, and to a lesser extent, in humans. To understand how genomic imprinting may
      affect development in other species, particularly those with a different mode of
      placental development from mice and humans, 339 sheep zygotes were
      micromanipulated to contain either 2 large (presumptive male) or 2 small
      (presumptive female) pronuclei. One hundred and twenty-seven of these embryos and
      86 manipulated and nonmanipulated control embryos were transferred to recipient
      ewes over 3 breeding seasons. Twenty-one control and 7 experimental conceptuses
      were recovered on day 21. Four of these conceptuses derived from zygotes with 2
      small pronuclei were identified by karyotyping to be gynogenones (maternal
      derived genome). While the gross morphology of the embryos appeared no different
      to those of normal controls, the extra-embryonic tissue from the conceptuses
      showed some hypertrophy and hypervascularization. Preliminary Northern blots of
      mRNA from allantoic and trophoblast tissue showed an overexpression of H19 and an
      underexpression of IGF2. Although the sheep gynogenetic phenotype contrasts with
      that seen in mice, these two genes appear to be similarly differentially
      expressed.

PMID- 9590532
TI  - Distribution of PNP 14 (beta-synuclein) in neuroendocrine tissues: localization
      in Sertoli cells.
AB  - Phosphoneuroprotein (PNP 14) is abundant in the central nervous system and is
      localized at nerve endings but not in synaptic vesicles. In this study, we
      examined the presence of PNP 14 in various endocrine tissues of the rat. PNP 14
      was not detected in the endocrine cells of the intestine, testes, or adrenal
      gland, but it was present in axon terminals in both the medulla of the adrenal
      gland and the anterior pituitary gland. When testes were stained with PNP 14
      specific antibodies by an indirect immunofluorescence method, PNP 14 was found in
      Sertoli cells of the testes, associated with fibrillar structures. PNP 14 was
      also detected in cultured Sertoli cells with a fibrillar pattern in the cytoplasm
      and around the nuclei. The fibrillar structure did not resemble actin stress
      fibers, microtubules, or intermediate filaments. The amount of PNP 14 in the
      testis changed with development. It increased markedly during the first 4 weeks
      after birth and then decreased. During the first 4 weeks after birth,
      spermatogonia undergo two rounds of meiosis. It is possible, therefore, that PNP
      14 might be a factor related to meiosis.

PMID- 9590533
TI  - Steroid production, cell proliferation, and apoptosis in cultured bovine antral
      and mural granulosa cells: development of an in vitro model to study estradiol
      production.
AB  - This study was undertaken to characterize the relationship between changes in
      steroid production, cell cycle activity (ie, cell proliferation) and apoptosis in
      antral and mural bovine granulosa cells cultured in vitro. This was done to
      select conditions promoting optimal estradiol production by bovine granulosa
      cells cultured in completely defined conditions. In the first experiment, antral
      granulosa cells were cultured over the entire 4 days of the culture period in the
      presence of either 0, 2, or 10 ng/ml of FSH (chronic conditions) or were
      maintained under minimal FSH support (0.5 ng/ml FSH) for the first 3 days of
      culture and then were challenged over the fourth day of culture with either 0, 2,
      or 10 ng/ml FSH (challenged conditions). Compared with cells exposed to constant
      FSH levels (chronic conditions), the FSH-induced production of estradiol was
      higher (P < 0.006) and that of progesterone was lower (P < 0.02) over the last 24
      h of culture, when antral granulosa cells were maintained under minimal FSH
      support during the first 3 days of culture (challenged conditions). In the second
      experiment, dynamics of estradiol and progesterone productions, conversion of
      [14C]androstenedione into subsequent steroid metabolites, DNA content, cell cycle
      activity, and apoptosis (as assessed by flow cytometry) of antral and mural
      granulosa cells over the first 3 days of culture under minimal FSH support and in
      response to a challenge with FSH during the last 24 h of culture were evaluated.
      Estradiol production as well as the conversion of androstenedione into
      testosterone and estradiol were greater (P < 0.01) in antral than in mural
      granulosa cells cultured under challenged conditions. A higher proportion of
      mural than antral granulosa cells were in the proliferative state at the end of
      culture (P < 0.03). This may be related to the decreased ability of mural cells
      to produce estradiol. FSH suppressed (P < 0.05) the spontaneous onset of
      apoptosis in both cell types. These results suggest that functional differences
      between these two cell compartments need to be considered in studying bovine
      granulosa cells in vitro. Because of their large (400 to 600%) FSH-induced
      estradiol production, antral granulosa cells cultured under challenged conditions
      provide a model that can be used to examine substances for their ability to alter
      estradiol production and apoptosis in bovine granulosa cells.

PMID- 9590534
TI  - Casein kinase II activity of buffalo sperm chromatin.
AB  - Two cyclic AMP-independent protein kinase activities have been found associated
      with buffalo sperm chromatin: a histone kinase highly specific for arginine-rich
      histone was reported recently (Mudgal et al., 1997: Arch Andrology 38:191-199)
      and a casein kinase II is described here. Casein kinase activity was solubilized
      with 0.35 M NaCl, which extracted 90% of the initial enzyme activity associated
      with buffalo sperm chromatin. Of the two acidic proteins tested, casein was
      preferred substrate over phosvitin. Among the casein fractions, the order of
      preference for casein kinase was beta-casein > alpha-casein > casein. Cyclic AMP
      at concentrations up to 50 microM had no effect on the phosphorylation of casein.
      Phosphoamino acid analysis using casein as the substrate showed threonine to be
      the acceptor amino acid for phosphoester link. Phosphorylation specificity was
      determined by phosphorylating buffalo beta-casein followed by the preparation of
      tryptic peptides and identification of amino acid residue phosphorylated.
      Threonine residue at position 41 having clusters of acidic amino acid residues
      (Thr. Glu. Asp. Glu) C-terminal to it was phosphorylated, a phosphorylation
      specificity akin to CKII. It is thought that phosphorylation of histones
      decreases their association with DNA and probably makes the DNA more available
      for replication, while phosphorylation of nonhistone proteins modifies their
      interaction with histones, allowing control of template activity. Two protein
      kinases found in buffalo sperm chromatin may perform a similar function.

PMID- 9590535
TI  - The effect of recipient oocyte volume on nuclear transfer in cattle.
AB  - This study compared the developmental potential of bovine nuclear transfer
      embryos with varying amounts of cytoplasm. Embryos formed from single cytoplasts
      fused to blastomeres by a single electrical pulse or from double cytoplasts using
      a double electrical pulse resulted in reconstituted embryos containing 75% and
      150% of the original oocyte volume. No differences in fusion, cleavage, or
      development rates to blastocysts were observed between the groups. Mean cell
      numbers 2 days after fusion were significantly lower in single-cytoplast clones.
      Cell numbers of resulting blastocysts were likewise significantly lower in single
      cytoplast clones. Embryos formed by fusion of blastomeres with single cytoplasts
      using a single electrical pulse or from double cytoplasts using either a single
      or a double pulse resulted in reconstituted embryos containing 50%, 100% and 100%
      of the original oocyte volume. Again, no differences in fusion or cleavage rates
      were observed between groups, but the development to blastocysts at day 7 was
      significantly higher in double cytoplasts constructed with one fusion pulse than
      in single cytoplasts (P < 0.05). Mean cell numbers 2 days after fusion were
      significantly lower in single-cytoplast clones (P < 0.05), but at the blastocyst
      stage, no statistically significant differences in cell numbers were observed.
      The results of this study show that cytoplasmic volume plays a role in the
      development of nuclear transfer embryos. When using crude enucleation methods
      such as oocyte bisection, normal cytoplasmic volumes can be achieved by fusing
      double cytoplasts with embryonic blastomeres.

PMID- 9590536
TI  - A detailed analysis of pronucleus development in bovine zygotes in vitro: cell
      cycle chronology and ultrastructure.
AB  - The aim of the present experiment was to analyze the chronology of pronucleus
      development and DNA synthesis, as well as the ultrastructure of intranuclear
      bodies, in bovine zygotes produced in vitro. Bovine oocytes were matured and
      fertilized in vitro, and sperm penetration and pronucleus development were
      examined. DNA synthesis was investigated by sequential incubation with [3H]- and
      [14C]thymidine followed by autoradiography on semithin sections. Ultrathin
      sections for transmission electron microscopy were prepared from the same
      zygotes. Sperm penetration was noted for the first time at 4 hr after in vitro
      insemination and reached a maximum at 6 hr. Pronucleus formation was initiated at
      4 hr, and up to at least 11 hr the maternal pronucleus was more developed than
      its paternal counterpart. DNA synthesis was initiated at 14-15 hr, and the S
      phase lasted for 8-10 hr. The most prominent ultrastructural entities of the
      pronuclei were the nucleolus precursor bodies (NPBs). During the S- and G2
      phases, the NPBs spatially associated with clusters of interchromatin-like
      granules. The two components were firmly attached to each other by an electron
      dense reticulum. During the late G2-phase, the NPBs were apparently detached from
      the interchromatin-like granules and the electron-dense reticulum again. The
      interaction between the intranuclear bodies and granules appears to be comparable
      with the situation previously described for in vivo-produced bovine zygotes (J
      Laurincik et al., Mol Reprod Dev 43:62-69, 1996), except for the lack of
      vacuolization of the NPBs during the S-phase in vitro.

PMID- 9590537
TI  - Theca cell monolayers that inhibit maturation of bovine oocytes show differences
      in their protein secretion pattern.
AB  - A previous study reported that coculturing bovine cumulus-oocyte complexes (COCs)
      with theca cell monolayers maintained oocytes in meiotic arrest. The present
      study evaluated whether the protein secretion pattern in this system is different
      between theca cells and granulosa cells and whether the presence of COCs
      influences their pattern of secretion. Follicular cells were isolated from 2- to
      5-mm follicles and cultured in TCM-199 supplemented with 10% fetal calf serum.
      Theca cell monolayers maintained COCs but not denuded oocytes (DOs) in meiotic
      arrest. Monolayers were incubated for 6 hr in medium supplemented with
      radioactive L-[35S]methionine. The patterns of protein secreted in the medium
      were analyzed by electrophoresis SDS-PAGE 10%. These results showed that theca
      cell monolayers secreted two major proteins. This pattern was different from the
      protein pattern secreted by granulosa cell monolayers. The molecular weights of
      these proteins were estimated to be 214 and 190 kDa. Coculturing COCs with theca
      cell monolayers during the labeling revealed that COCs modulated the secretion of
      theca cell monolayers. When theca cells were grown on collagen-coated wells, the
      monolayers did not maintain the oocytes at the germinal vesicle (GV) stage. The
      secretion of the 214-kDa protein also decreased. Then, when theca cell monolayers
      are effective to maintain oocytes in meiotic arrest, the cells especially
      secreted the 214-kDa protein. In conclusion, the 214-kDa protein secreted by
      theca cell monolayers may play a role in the process of maintaining oocytes in
      meiotic arrest.

PMID- 9590538
TI  - Rearrangement of the PH-20 protein on the surface of macaque spermatozoa
      following exposure to anti-PH-20 antibodies or binding to zona pellucida.
AB  - Capacitated cynomolgus macaque sperm have a surface hyaluronidase (PH-20) that is
      evenly distributed over the entire head and can be visualized at the
      ultrastructural level using a secondary antibody labeled with colloidal gold .
      Exposure of sperm to mono-specific, bivalent polyclonal antibodies to PH-20
      causes a rapid clustering of PH-20. The predominant morphological consequence of
      PH-20 redistribution is its aggregation along the lateral edge of the sperm head.
      Monovalent Fab fragments of the anti-PH-20 antibody bound to the sperm head but
      did not induce a change in PH-20 distribution. PH-20 aggregation was observed in
      almost all sperm following treatment with the polyclonal antibody, but only about
      20% of the sperm had morphological acrosome reactions, regardless of the time of
      exposure or the concentration of antibody. There was morphological evidence of
      swelling of the acrosomal matrix in over 50% of the sperm following exposure to
      anti-PH-20 antibodies. Anti-PH-20 Fab fragments did not induce the acrosome
      reaction or acrosomal matrix swelling. Sperm bound to macaque zona pellucida also
      showed aggregation of the PH-20 protein as soon as 30 sec after sperm-zona
      interaction. This aggregation was not observed when macaque sperm were bound to
      hamster zona pellucida. When macaque sperm were surface-labeled with biotin and
      then incubated with anti-PH-20 antibodies or macaque zona pellucida, there was no
      evidence of a global surface protein rearrangement, although PH-20 protein was
      aggregated on the surface of the same sperm cells. An increase in levels of
      internal sperm Ca++ was measured in association with the antibody-induced PH-20
      aggregation. Fab fragments did not increase Ca++ levels, but when they were
      crosslinked with anti-Fab antibody there was a significant Ca++ increase and
      induction of acrosome reactions. Anti-PH-20 Fab fragments did not block macaque
      sperm binding to macaque zona pellucida or the zona-induced acrosome reaction. We
      conclude that PH-20 on the sperm surface is involved in sperm-zona pellucida
      interaction and the zona-induced acrosome reaction.

PMID- 9590539
TI  - Microtubule and chromatin organization during the first cell-cycle following
      intracytoplasmic injection of round spermatid into porcine oocytes.
AB  - The objective of this study was to determine microtubule assembly and chromatin
      configuration in porcine oocytes during the first cell cycle following round
      spermatid injection into matured porcine oocytes in the presence or absence of
      electrical stimulation. The oocytes with two large pronuclei and two polar bodies
      were classified as normal fertilization at 6 to 8 h following injection. The
      incidence of normal fertilization following round spermatid injection with
      electrical stimulation was significantly higher (21/45, 47%) than that following
      injection alone (6/39, 15%). Although a small microtubular aster was organized
      near the decondensed spermatid chromatin in some oocytes (2/6, 33%, spermatid
      injection alone; 9/21, 29%, spermatid injection and electrical stimulation), it
      did not enlarge nor fill the cytoplasm. Instead, a dense network of microtubules
      in the cytoplasm was organized from cortex. At 12 to 15 h after injection, we
      classified the oocytes with closely apposed pronuclei as normal fertilization.
      The electrical stimulation following spermatid injection enhanced (P < 0.05) the
      incidence of normal fertilization (18/54, 33%) compared with spermatid injection
      alone (7/52, 13%). During pronuclear movement, the maternally derived
      microtubules filled the whole cytoplasm, which appeared to move male and female
      chromatin. Mitosis and two-cell division were observed at 20 to 24 h after
      spermatid injection with electrical stimulation (12/41, 29%). At mitotic
      metaphase, the microtubular spindle had focused astral poles, and chromosomes
      were aligned on the spindle equator. During mitosis, asters were assembled at
      each spindle pole, and they filled the cytoplasm. These results suggested that
      round spermatid nuclei of the pig can develop into a morphologically normal
      pronucleus in matured porcine oocytes and are competent to participate in syngamy
      with the ootid chromatin. In addition, functional microtubules for complete
      fertilization with spermatid were not associated with male-derived centrosome but
      were organized solely from maternal stores.

PMID- 9590540
TI  - Molecular cloning and expression in Escherichia coli of cDNA encoding bonnet
      monkey (Macaca radiata) zona pellucida glycoprotein-ZP2.
AB  - Zona pellucida (ZP) glycoproteins have been proposed as candidate antigens for an
      immunocontraceptive vaccine. The efficacy of such a vaccine has to be evaluated
      in nonhuman primates, thus necessitating the characterization of their ZP
      glycoproteins. A bonnet monkey (Macaca radiata) ovarian cDNA lambda gt11 library
      was screened for ZP2 (bZP2) using full-length human ZP2 cDNA as a probe. Two
      identical full-length clones with an open reading frame of 2235 nt encoding a
      polypeptide of 745 aa residues were isolated. The deduced aa sequence of bZP2
      revealed high sequence identity (94.2%) with human ZP2. The bZP2 cDNA (115-1914
      nt, 1.8 kb), excluding sequences coding for N-terminal signal sequence and C
      terminal transmembranelike domain, was PCR amplified and Sac1-Sal1 restricted
      fragment cloned in frame downstream of the T5 promoter under the lac operator
      control in a pQE-30 vector. Recombinant bZP2 (r-bZP2) was expressed as a
      polyhistidine fusion protein in Escherichia coli strain M15 [pREP4]. Immunoblot
      with rabbit polyclonal antibodies against bZP2 synthetic peptide (corresponding
      to aa residues 429-444; K434 replaced by R and 1436 by V) revealed a major band
      of 68 kDa. Immunization of male rabbits with the r-bZP2 protein purified on Ni
      NTA resin under denaturing conditions generated antibodies reactive with r-bZP2
      in ELISA as well as with native protein as revealed by positive fluorescence of
      ZP of bonnet monkey ovary. The availability of r-bZP2 and its aa sequence will
      help in the development and evaluation of a contraceptive vaccine based on ZP2.

PMID- 9590542
TI  - Ovarian hormones influence the morphology, distribution, and density of tyrosine
      hydroxylase immunoreactive axons in the dorsolateral prefrontal cortex of adult
      rhesus monkeys.
AB  - The maturation, adult functioning and dysfunction of the prefrontal cortex in
      disorders such as schizophrenia show gender biases in human and non-human
      primates. Although the basis for the hormone influence suggested in these
      observations is unknown, one possibility is that circulating hormones stimulate
      catecholamine innervation in the frontal lobe. This innervation is essential for
      prefrontal cortical function, and gonadal, especially ovarian hormones,
      profoundly influence catecholamine function and physiology in subcortical
      structures. This study was undertaken to determine whether influence is also
      exerted upon the catecholamine innervation of the association cortex by combining
      ovarian hormone manipulation with immunocytochemistry for tyrosine hydroxylase in
      the dorsolateral prefrontal cortex of adult female macaque monkeys. Qualitative
      and quantitative analyses of immunoreactive fibers were carried out and compared
      in cortices of ovariectomized animals, ovariectomized animals treated with
      estrogen, ovariectomized animals treated with estrogen followed by progesterone,
      and in intact, age- and sex-matched controls. These analyses revealed striking,
      layer-specific anomalies in fiber morphology and profound reductions in fiber
      density in ovariectomized animals. While hormone replacement with estrogen alone
      had limited influence, estrogen followed by progesterone was particularly
      effective in restoring tyrosine hydroxylase innervation in ovariectomized
      animals. Thus, ovarian hormones appear to be potent regulators of the
      catecholamine innervation of the primate prefrontal cortex. Such regulation is
      anticipated in the gender differences observed in prefrontal cortical development
      and function, and may also be relevant for the prefrontal dysfunction in
      disorders such as schizophrenia.

PMID- 9590541
TI  - SPIN, a substrate in the MAP kinase pathway in mouse oocytes.
AB  - The newly cloned gene Spin encodes a 30-kDa protein, a well-defined abundant
      molecule found in mouse oocytes and early embryos. This protein SPIN undergoes
      metaphase-specific phosphorylation and binds to the spindle. To understand the
      role of SPIN in oocyte meiosis, oocytes were treated with drugs that affect the
      cell cycle by activating or inactivating specific kinases. The posttranslational
      modification of SPIN in the treated oocytes was then investigated by one- and two
      dimensional gel electrophoresis. Modification of SPIN is inhibited by treatment
      with 6-dimethylaminopurine (DMAP), suggesting that SPIN is phosphorylated by a
      serine-threonine kinase. Furthermore, SPIN from cycloheximide-treated oocytes
      that lack detectable MAP kinase activity is only partially phosphorylated,
      indicating that SPIN may be phosphorylated by the MOS/MAP kinase pathway. To
      confirm this observation, SPIN was analyzed in Mos-null mutant mice lacking MAP
      kinase activity. Normal posttranslational modification of SPIN did not occur in
      Mos-null mutant oocytes. In addition, there is reduced association of SPIN with
      the metaphase I spindle in Mos-null mutant oocytes, as determined by
      immunohistochemical analysis. These findings suggest that SPIN is a substrate in
      the MOS/ MAP kinase pathway and further that this phosphorylation of SPIN may be
      essential for its interaction with the spindle.

PMID- 9590543
TI  - Timed markers for the differentiation of the cuticular plate and stereocilia in
      hair cells from the mouse inner ear.
AB  - The differentiation of the cuticular plate and stereocilia in cochleovestibular
      hair cells from the mouse was traced with monoclonal antibodies raised by in
      vitro immunization. The cuticular plate is detected first from embryonic days 14
      15 (E14-E15), before cell differentiation is apparent, either with scanning
      electron microscopy or with actin filament labeling. A flat disc of material
      forms beneath the apical membrane and subsequently expands, forming a fully
      shaped cuticular plate at postnatal stages 3-5 (P3-P5). A second antibody labels
      stereocilia from stage E16 to E18. In the cochlea, the label initially appears as
      a punctate disc on the cell apex and then follows the development of the
      stereocilia until the adult shape of the bundle forms at P4-P6. Additional
      antibodies label stereocilia from P4 to P6 and are apparently specific for the
      inner ear. They do not label the cuticular plate at any stage and do not cross
      react with tissues of muscle, kidney, eye, tongue, gut, skin, or brain. At stage
      P12-P14, coinciding with the functional maturity of the ear, they label the
      apical regions of Deiter's cells. The temporally overlapping sequence of antibody
      labeling sheds new light on the development of the hair cell apex and allows us
      to monitor the differentiation of hair cells from their last mitotic division to
      the initiation of organ function, a period of over 2 weeks.

PMID- 9590544
TI  - Subcortical connections of normotopic and heterotopic neurons in sensory and
      motor cortices of the tish mutant rat.
AB  - Orthograde and retrograde tracers were used to examine subcortical connections of
      neurons in the neurological mutant tish rat. This animal exhibits bilateral
      heterotopia similar to those observed in epileptic humans with subcortical band
      heterotopia. Terminal varicosities were labeled in the striatum, thalamus,
      brainstem, and spinal cord following injections of the anterograde tracer
      biotinylated dextran amine (BDA) into the heterotopic cortex. The general
      topography of corticothalamic projections was evaluated by injecting the
      retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde
      labeling of small-to-medium sized neurons was observed in layer VI of
      topographically restricted portions of the normotopic cortex. Similar appearing
      cells were labeled in the neighboring portions of the underlying heterotopia;
      however, these neurons did not display characteristic lamination or radial
      orientation. Thalamocortical terminals labeled by injecting BDA into the
      ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the
      medial aspect of the normotopic somatosensory cortex. In contrast, a radial
      column of terminals was present in the underlying heterotopia. Typical barrel
      labeling was found in the lateral aspect of the normotopic somatosensory cortex
      after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse
      patches of labeling were observed in the underlying heterotopia. Heterotopic
      neurons in the tish cortex, thus, exhibit characteristic features of subcortical
      connectivity. Both normotopic and heterotopic neurons in the tish brain project
      to appropriate subcortical sites and establish bidirectional topographic
      connections with the thalamus. These results suggest that primary sensory-motor
      information is represented in a parallel manner in the normotopic and heterotopic
      cortices of the tish rat.

PMID- 9590545
TI  - Alpha subunit of Go localizes in the dendritic tips of ON bipolar cells.
AB  - The metabotropic glutamate receptor (mGluR6), expressed by rod bipolar cells and
      ON cone bipolar cells, activates a trimeric guanine nucleotide-binding protein (G
      protein) that ultimately closes a cation channel. The G-protein remains
      unidentified, but the alpha subunit of Go (Go(alpha)) has been suggested as a
      candidate because it is present in rod bipolar cells. However, the precise
      subcellular distribution of Go within the rod bipolar cell, and its distribution
      among cone bipolar cells was not determined. This information is important in
      assessing the hypothesis that Go couple mGluR6 to its effector. Here I report the
      distribution of Go (alpha subunit) by immunostaining in several mammalian
      retinas. The overall distribution is conserved across mammalian species:
      strongest in the dendrites of ON bipolar cells, moderate in their somas, weak in
      their axons, and absent from their terminals. Go(alpha) is also present in some
      amacrine somas and processes. In monkey fovea, where rods and rod bipolar cells
      are absent, Go(alpha) is present in about half of the bipolar somas which occupy
      the upper tiers of the bipolar layer, and are therefore identified as ON cone
      bipolar cells. Ultrastructurally, in monkey and cat, Go(alpha) is present in the
      dendritic tips of rod bipolar cells and ON cone bipolar cells, which are
      identified by their invaginating contacts. It is absent from OFF cone bipolar
      dendrites, which are identified by their flat contacts. It is also absent from
      axons entering the inner plexiform layer, and their terminals. In the primary
      dendrites, stain for Go(alpha) mainly associates with the plasma membrane, but in
      the dendritic tips it is also present in the cytosol. Apparently, Go(alpha) is
      expressed by the same bipolar cells that also express mGluR6, and is concentrated
      at the same subcellular location. Thus, Go(alpha) could serve to couple mGluR6 to
      later stages of its signaling cascade.

PMID- 9590546
TI  - Intrinsic connections of the rat amygdaloid complex: projections originating in
      the central nucleus.
AB  - Inputs from the amygdaloid and extraamygdaloid areas terminate in various
      divisions of the central nucleus. To elucidate the interconnections between the
      different regions of the central nucleus and its connectivity with the other
      amygdaloid areas, we injected the anterograde tracer, Phaseolus vulgaris
      leucoagglutinin (PHA-L) into the capsular, lateral, intermediate, and medial
      divisions of the central nucleus in rat. There were a number of labeled terminals
      near the injection site within each division. The intrinsic connections between
      the various divisions of the central nucleus were organized topographically and
      originated primarily in the lateral division, which projected to the capsular and
      medial divisions. Most of the connections were unidirectional, except in the
      capsular division, which received a light reciprocal projection from its efferent
      target, the medial division. The intermediate division did not project to any of
      the other divisions of the central nucleus. Extrinsic projections from the
      central nucleus to the other amygdaloid nuclei were meager. Light projections
      were observed in the parvicellular division of the basal nucleus, the anterior
      cortical nucleus, the amygdalohippocampal area, and the anterior amygdaloid area.
      No projections to the contralateral amygdala were found. These data show that the
      central nucleus has a dense network of topographically organized intradivisional
      and interdivisional connections that may integrate the intraamygdaloid and
      extraamygdaloid information entering the different regions of the central
      nucleus. The sparse reciprocal connections to the other amygdaloid nuclei suggest
      that the central nucleus does not regulate the other amygdaloid regions but,
      rather, executes the responses evoked by the other amygdaloid nuclei that
      innervate the central nucleus.

PMID- 9590548
TI  - Remodeling of lesioned kitten visual cortex after xenotransplantation of fetal
      mouse neopallium.
AB  - Remodeling of the mechanically injured cerebral cortex of kittens was studied in
      the presence of a neural xenograft taken from mouse fetuses. Solid neural tissue
      from the neopallium of a 14-day-old fetus was transferred into a cavity prepared
      in visual cortical area 18 of 33-day-old kittens. Injections of bromodeoxyuridine
      (BrdU) were used to monitor postoperative cell proliferation. Two months after
      transplantation, the presence of graft tissue in the recipient brain was assessed
      by Thy-1 immunohistochemistry. Antibodies specific for neurons, astrocytes, and
      oligodendrocytes and hematoxylin staining for endothelial cells were used for the
      characterization of proliferating (BrdU+) cells. The following were the major
      observations: 1) Of ten transplanted kittens, four had the cavity completely
      filled with neural tissue that resembled the intact cerebral cortex in its
      cytoarchitecture, whereas, in four other kittens, the cavity was partially
      closed. In two kittens, the cavity remained or became larger, which was also the
      case with all four sham-operated (lesioned, without graft) animals. 2) A
      substantial part of the remodeled tissue was of host origin. Only a few donor
      cells survived and dispersed widely in the host parenchyme. 3) In the remodeled
      region of transplanted animals, the densities of nerve, glial, and endothelial
      cells were similar to those in intact animals. 4) Cell proliferation increased
      after transplantation but only within a limited time, because, 2 months after the
      operation, the number of mitotic cells in the grafted cerebral cortex did not
      differ from that in intact controls. Our data suggest that the xenograft evokes
      repair processes in the kitten visual cortex that lead to structural recovery
      from a mechanical insult. The regeneration seems to rely on a complex interplay
      of many different mechanisms, including attenuation of necrosis, cell
      proliferation, and immigration of host cells into the wounded area.

PMID- 9590547
TI  - Expression of nerve growth factor and neurotrophin-3 mRNAs in hippocampal
      interneurons: morphological characterization, levels of expression, and
      colocalization of nerve growth factor and neurotrophin-3.
AB  - We have investigated the distribution and morphology of hippocampal interneurons
      that express the neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT
      3) in the rat. For this study, we combined in situ hybridization for the
      detection of NGF and NT-3 mRNAs and immunocytochemistry against the calcium
      binding proteins parvalbumin (PARV), calretinin (CALR), and calbindin (CALB).
      Whereas the majority of PARV+ interneurons expressed NGF mRNA, only subsets of
      CALR- and CALB-immunoreactive interneurons (23% and 24%, respectively) displayed
      NGF hybridization. Most CALB/NGF+ cells were located in the stratum oriens/alveus
      of the CA3-CA1 regions, suggesting that they may include the population of CALB+,
      hippocamposeptal, nonpyramidal neurons. Most of the nonspiny CALR/NGF+ neurons
      were located within or in the vicinity of the pyramidal layer and had faint CALR
      immunostaining and stellate, thin dendrites. Regarding the spiny CALR
      immunoreactive cells, we found that most of these neurons in the hilus were NGF+,
      whereas only 59% of displayed NGF hybridization in the stratum lucidum of the CA3
      region. A small subset of PARV- and CALR-immunoreactive cells expressed NT-3 mRNA
      (16% and 13%, respectively). NT-3 message was not found in the large basket cells
      of the dentate gyrus, whereas the distribution and morphology of CALR/NT-3+ cells
      were similar to those of nonspiny CALR/NGF+ cells. In fact, double in situ
      hybridization analysis confirmed that most NT-3+ neurons also expressed NGF mRNA,
      indicating coexpression of both neurotrophins in subpopulations of PARV+ and
      CALR+ neurons. Moreover, the level of NGF mRNA expression was higher in PARV+
      neurons than in CALR- and CALB-immunoreactive interneurons, whereas NT-3 message
      was expressed similarly in PARV+ and CALR+ neurons. The present findings show a
      differential expression of NGF and NT-3 mRNAs in subsets of hippocampal
      interneurons and suggest that the expression of these transcripts depends on
      factors intrinsic to particular cell types.

PMID- 9590549
TI  - Cytological compartmentalization in the staggerer cerebellum, as revealed by
      calbindin immunohistochemistry for Purkinje cells.
AB  - The staggerer mouse carries a deletion in a gene encoding the nuclear hormone
      receptor RORalpha, which leads to severe impairments in phenotypic
      differentiation of cerebellar Purkinje cells. We previously found parasagittal
      compartments in the mature staggerer cerebellum, as defined by different
      transcription levels of Purkinje cell-specific molecules including calbindin. In
      the present study, we developed a hightiter anti-calbindin antibody to examine
      morphological features of the staggerer Purkinje cells. Immunohistochemistry for
      calbindin revealed compartmentalized Purkinje cell populations with different
      cell sizes, alignments, cell densities, and dendritic arborization, as well as
      different immunoreactivities, corresponding to the "transcriptional"
      compartments. Based on these immunohistochemical and cytological characteristics,
      the rostral cerebellum was clearly subdivided into three to seven parasagittal
      zones (Zones I-VII). Purkinje cells in Zones I and III were associated with the
      strongest calbindin immunoreactivities and exhibited morphological features
      reminiscent of the wild-type cells, i.e., large flask-shaped cell bodies,
      monolayer alignment, and arborized dendrites. Purkinje cells in Zone V were also
      labeled strongly, but they were small in cell size, ectopic and possessed long
      unbranched dendrites. On the other hand, Purkinje cells in Zones II, IV, and VI
      were very low in calbindin immunoreactivity and marked by small cell size,
      ectopia, poorly-developed dendrites and low cell density. Considering that this
      unique cytological compartmentalization emerges as the result of RORalpha gene
      mutation, it is suggested that normal cytodifferentiation of Purkinje cells is
      governed by both RORalpha-dependent and -independent mechanisms, and further that
      the latter mechanism might exert unevenly along the mediolateral cerebellar axis.

PMID- 9590551
TI  - Embryonic expression of pituitary adenylate cyclase-activating polypeptide in
      sensory and autonomic ganglia and in spinal cord of the rat.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide that
      is related structurally to vasoactive intestinal polypeptide (VIP), has been
      shown to stimulate neuronal growth and differentiation, indicating a possible
      function in the development of the nervous system. Studies have indicated that
      the PACAP receptor is expressed during development, but data on PACAP expression
      are limited mainly to postnatal development. In the present study, we used
      immunohistochemistry and in situ hybridization histochemistry to examine the
      expression of PACAP in autonomic and sensory ganglia and spinal cord of rat
      fetuses at embryonic days 12-21 (E12-E21). PACAP immunoreactivity was visualized
      by using a specific monoclonal anti-PACAP antibody to detect both PACAP-38 and
      PACAP-27, and PACAP mRNA was visualized by using a [33P]-labeled cRNA-probe.
      PACAP- nerve fibers were observed in the spinal cord as early as E13. At E14,
      PACAP-immunoreactive nerve fibers projected to the sympathetic trunk, where few
      PACAP- nerve cell bodies were seen from E15. On the same embryonic day, PACAP
      immunoreactive nerve cell bodies appeared in the intermediolateral column of the
      spinal cord. From E15 to E16, PACAP-immunoreactive nerve cell bodies were visible
      within sensory and autonomic ganglia, such as the dorsal root, the trigeminal,
      the sphenopalatine, the otic, the submandibular, and the nodose ganglia. At E16,
      PACAP+ nerve fibers were innervating the adrenal medulla, and immunoreactive
      fibers could also be observed in the superior cervical ganglion, in which PACAP
      immunoreactive cell bodies were detected occasionally from E18. The synthesis of
      PACAP in neuronal cell bodies was confirmed by the demonstration of PACAP mRNA
      with in situ hybridization histochemistry. Thus, in all of the structures
      examined, PACAP appeared at roughly the same embryonic stage and, thereafter,
      increased to the adult level before birth. Because PACAP occurred with the same
      distribution pattern as that described in the adult rat, there is no evidence for
      transient expression. The early expression of PACAP suggests a possible role for
      the peptide in the developing nervous system.

PMID- 9590550
TI  - Distribution of TAG-1 and synaptophysin in the developing cerebellar cortex:
      relationship to Purkinje cell dendritic development.
AB  - During postnatal cerebellar development, differentiating Purkinje cell (PC)
      dendrites extend towards the pial surface and progressively contact immature
      granule cell parallel fiber (PF) axons in the deep external granule layer (EGL),
      thus forming a zone of synaptic contact called the molecular layer (ML). The
      neuronal cell adhesion molecule, TAG-1, is transiently expressed on PF axons in
      the deep EGL (Yamamoto et al. [1986] J. Neurosci. 12:3576-3594). To determine the
      spatiotemporal relationship between Purkinje cell dendritic differentiation and
      the cessation of TAG-1 expression, sagittal sections from developing rat
      cerebellum were double-labeled for TAG-1 and the Purkinje cell-specific marker,
      calbindin, by using indirect immunofluorescence. At postnatal day 2 (P2) and P5,
      confocal microscopy revealed that TAG-1 immunoreactivity began above the furthest
      superficial extent of the Purkinje cell apical dendritic cap. By P10, PC
      dendrites penetrated partially into the TAG-1-positive deep EGL, creating a
      narrow region of overlap in TAG-1/calbindin staining at the deep EGL/ML border.
      In contrast, at P15 and P20, TAG-1 staining began directly above the furthest
      superficial extent of the Purkinje cell dendrites, with little or no overlap in
      TAG-1/calbindin staining. Staining for the synaptic vesicle glycoprotein,
      synaptophysin, was dim throughout most of the TAG-1-positive deep EGL, although
      bright synaptophysin immunoreactivity was observed throughout the ML. Overlap in
      TAG-1/synaptophysin staining was observed primarily at the deep EGL/ML border,
      suggesting that robust expression of synaptophysin in granule cells does not
      begin until after contact with Purkinje cell dendrites has been initiated. Our
      results suggest that factors present in the developing ML may influence the
      cessation of TAG-1 expression and the initiation of synaptophysin expression at
      the border region between the ML and the deep EGL.

PMID- 9590552
TI  - Multiple neurotrophic signals converge in surviving CA1 neurons of the gerbil
      hippocampus following transient forebrain ischemia.
AB  - Delayed cell death involving the CA1 area of the hippocampus was produced
      following 5 minutes of transient forebrain ischemia in gerbils. Cell death mainly
      affected CA1 pyramidal neurons, whereas parvalbumin-immunoreactive (parv-ir)
      cells were spared. Synaptophysin immunoreactivity was observed in the strata
      oriens and radiatum of CA1 for months, although immunoreactivity decreased in
      gerbils surviving 1 year post-ischemia. Golgi studies disclosed a few pyramidal
      neurons with dendrites, variably covered with dendritic spines, in the CA1 area
      of 1-year surviving gerbils. In the normal gerbil, the majority of CA1 neurons
      expressed brain-derived neurotrophic factor (BDNF), tyrosine protein kinase C
      (TrkC), fibroblast growth factor receptor 1 (Flg), transforming growth factor
      alpha (TGF-alpha), and epidermal growth factor-receptor (EGF-R), but only a
      minority of cells were tyrosine protein kinase B (TrkB)-immunoreactive. Marked
      reduction in the number of BDNF-, TrkC-, Flg-, TGF-alpha-, and EGF-R-ir cells was
      observed in CA1 from 24 hours to 1 year after ischemia. In contrast, TrkB-ir
      cells survived the ischemic insult. Double-labeling immunohistochemistry
      disclosed that about 90% of surviving BDNF-ir and 85% of TrkB-ir neurons co
      localized parvalbumin in the CA1 area. In control gerbils, only about 5% of BDNF
      ir cells in CA1 co-expressed TrkB. However, TrkB co-localized in about 95% of
      surviving BDNF-ir neurons in CA1 in ischemic gerbils. In addition, parvalbumin
      was co-expressed in about 90% of TrkC-, 95% Flg-, and 85% EGF-R-ir surviving
      neurons in the stratum pyramidale of CA1. Finally, basic fibroblast growth factor
      (bFGF) was expressed by reactive astrocytes from day 4 onwards. These data show
      that the subpopulation of TrkB-/parv-ir neurons in CA1 survive the ischemic
      episode and that multiple neurotrophic signals converge in surviving neurons of
      the gerbil hippocampus following transient forebrain ischemia.

PMID- 9590553
TI  - Regionalization defects in the weaver mouse cerebellum.
AB  - The mammalian cerebellum consists of parasagittal bands and transverse zones that
      are laid down early in development. When the adult cerebellum is immunostained
      for the Purkinje cell-specific antigen zebrin II (i.e., aldolase C),
      compartmentation is reflected in alternating zebrin II+ (P+) and zebrin II- bands
      (P ). The zebrin II phenotype is Purkinje cell autonomous; thus, disruptions in
      the zebrin pattern may reflect early problems in pattern formation. Zebrin II
      expression has been examined in the weaver (wv) mouse cerebellum. Both zebrin II-
      and zebrin II Purkinje cells are present in the homozygous weaver (wv/wv) mouse,
      but they are not distributed normally. In the posterior vermis, although the
      zebrin II+ bands are wider and multilaminate, the standard compartmentation is
      present. However, a large zebrin II+ cell mass is absent from the central vermis,
      and analysis of the anterior lobe reveals several missing zebrin II- bands. The
      cytoarchitectonic defects in wv mice are not simply related to the Purkinje cell
      abnormalities. Instead, serial reconstruction reveals two transverse boundaries
      one rostrally in lobule VI and the other caudally in lobule IX-that delineate
      cytoarchitectonic transverse zones important in cerebellar development. The
      abnormal zebrin expression pattern in wv/wv mice may be secondary to the deletion
      of a transverse zone. This is the first demonstration that Purkinje cell
      compartmentation can be altered by mutation; therefore, the wv mutation should
      prove valuable in understanding cerebellar regionalization.

PMID- 9590554
TI  - Retinoid signaling distinguishes a subpopulation of olfactory receptor neurons in
      the developing and adult mouse.
AB  - We asked whether retinoic acid (RA) influences olfactory receptor neurons (ORNs)
      in the developing and mature mouse olfactory epithelium (oe). The distribution of
      retinoid receptors and binding proteins in the oe changes between embryonic days
      11.5 and 13.5, the period when ORNs first differentiate and send axons into the
      nascent olfactory nerve. Coincident with this change, RA, which is produced in
      the frontonasal mesenchyme at these ages, begins to activate gene expression in a
      bilaterally symmetric subset of ORNs in the dorsolateral oe, as judged by the
      expression of an RA-responsive transgene. Axons from these RA-activated ORNs are
      segregated in the olfactory nerve as it extends through the frontonasal
      mesenchyme toward the forebrain. In vitro, RA potentiates ORN neurite growth on
      laminin, which, in the embryo, is found in a stripe of frontonasal mesenchyme
      directly associated with the olfactory nerve. RA does not modify growth on
      fibronectin, type IV collagen, or L1, which olfactory axons encounter in
      different regions of the territory between the olfactory epithelium and the
      brain. The pattern of RA-mediated transcriptional activation and axon segregation
      persists in early postnatal mice, and RA signaling can be recognized in a subset
      of adult ORNs in the dorsolateral oe. Thus, RA-mediated gene expression
      distinguishes a subpopulation of ORNs in a distinct region of the oe during the
      early development of the olfactory pathway, and may influence differentiation and
      axonal projections of ORNs in this region throughout life.

PMID- 9590555
TI  - Distribution of prolactin receptor immunoreactivity in the brain of estrogen
      treated, ovariectomized rats.
AB  - Although there is extensive evidence for effects of prolactin (PRL) on the brain,
      knowledge about the PRL receptor (PRL-R) in the brain is limited. By using
      monoclonal antibodies raised against purified rat liver PRL-R, the distribution
      of PRL-R was investigated by immunohistochemistry in brains of the estrogen
      treated ovariectomized (OVX+E) rat and the adult male rat. Immunohistochemistry
      was performed by using the avidin biotinylated horse radish peroxidase
      macromolecular complex method. In both male and OVX+E rats, strong immunostaining
      was detected in the choroid plexus of all cerebral ventricles. This
      immunostaining was localized predominately on epithelial cell membranes. In the
      OVX+E female rat, scattered immunoreactive perikarya were observed in the arcuate
      nucleus, periventricular hypothalamic nucleus, preoptic area, suprachiasmatic
      nucleus, and supraoptic nucleus of the hypothalamus. Immunostaining in
      hypothalamic nuclei was localized on neuronal cell bodies as well as on neuronal
      processes. In addition, there was extensive PRL-R immunoreactivity throughout the
      globus pallidus and ventral pallidum. Immunostaining in these striatal regions
      was not associated with neuronal cell bodies but appeared to be localized on
      processes or glial cells. In the male rat, less immunostaining was observed in
      the hypothalamus, and there was no immunostaining in the corpus striatum. No
      significant staining was observed in the cerebral cortex, thalamus, or hindbrain
      of either male or OVX+E rats. The implication of PRL-R existence in these brain
      regions remains to be investigated.

PMID- 9590556
TI  - Subdivisions of auditory cortex and ipsilateral cortical connections of the
      parabelt auditory cortex in macaque monkeys.
AB  - Auditory cortex of macaque monkeys can be divided into a core of primary or
      primary-like areas located on the lower bank of the lateral sulcus, a surrounding
      narrow belt of associated fields, and a parabelt region just lateral to the belt
      on the superior temporal gyrus. We determined patterns of ipsilateral cortical
      connections of the parabelt region by placing injections of four to seven
      distinguishable tracers in each of five monkeys. Results were related to
      architectonic subdivisions of auditory cortex in brain sections cut parallel to
      the surface of artificially flattened cortex (four cases) or cut in the coronal
      plane (one case). An auditory core was clearly apparent in these sections as a 16
      to 20-mm rostrocaudally elongated oval, several millimeters from the lip of the
      sulcus, that stained darkly for parvalbumin, myelin, and acetylcholinesterase.
      These features were most pronounced caudally in the cortex assigned to auditory
      area I, only slightly reduced in the rostral area, and most reduced in the
      narrower rostral extension we define as the rostrotemporal area. A narrow band of
      cortex surrounding the core stained more moderately for parvalbumin,
      acetylcholinesterase, and myelin. Two regions of the caudal belt, the caudomedial
      area, and the mediolateral area, stained more darkly, especially for parvalbumin.
      Rostromedial and medial rostrotemporal, regions of the medial belt stained more
      lightly for parvalbumin than the caudomedial area or the lateral belt. The
      parabelt region stained less darkly than the core and belt fields. Injections
      confined to the parabelt region labeled few neurons in the core, but large
      numbers in parts of the belt, the parabelt, and adjacent portions of the temporal
      lobe. Injections that encroached on the belt labeled large numbers of neurons in
      the core and helped define the width of the belt. Caudal injections in the
      parabelt labeled caudal portions of the belt, rostral injections labeled rostral
      portions, and both caudal and rostral injections labeled neurons in the
      rostromedial area of the medial belt. These observations support the concept of
      dividing the auditory cortex into core, belt, and parabelt; provide evidence for
      including the rostral area in the core; suggest the existence of as many as seven
      or eight belt fields; provide evidence for at least two subdivisions of the
      parabelt; and identify regions of the temporal lobe involved in auditory
      processing.

PMID- 9590557
TI  - Colocalization of nitric oxide synthase and some neurotransmitters in the
      intramural ganglia of the guinea pig urinary bladder.
AB  - The distribution of nitrergic neurons was investigated by using nicotinamide
      adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and nitric
      oxide synthase (NOS) immunohistochemistry in wholemount preparations of the
      urinary bladder in guinea pigs. Both NADPH-d+ and NOS+ neurons were located
      predominantly in the bladder base. Double staining showed that 70.9% of the NADPH
      d+ neurons coexpressed NOS. Acetylcholinesterase histochemistry revealed that a
      majority of the intramural neurons were reactive, and about half of them (51.4%)
      were double labelled for NOS. Tyrosine hydroxylase-positive neurons were also
      distributed mainly in the bladder base but in a neuronal population that was
      separate from the preponderant NADPH-d+ neurons. Vasoactive intestinal
      polypeptide immunoreactivity was also detected in the some of intramural ganglion
      cells, in which 21.3% of them coexpressed NADPH-d. Calcitonin gene-related
      peptide and substance P immunoreactivities were confined to nerve fibers, often
      in close association with NADPH-d+ cells or extended along the blood vessels.
      These results have demonstrated the colocalization of NADPH-d and NOS in the
      majority of intramural ganglion cells. Many of the nitrergic neurons are
      apparently cholinergic, indicating that they are parasympathetic postganglionic
      neurons, and this underscores NO as the major neuromodulator in the
      parasympathetic nerves in the bladder walls. The localization of vasoactive
      intestinal polypeptide in nitrergic neurons suggests that the peptide may
      complement NO for regulation of micturition reflex. The close relationship of
      NADPH-d-reactive intramural neurons with calcitonin gene-related peptide and
      substance P fibers, most probably derived from dorsal root ganglion cells,
      suggests that NO released from the local neurons may exert its influence on the
      sensory neural pathways in the urinary bladder.

PMID- 9590558
TI  - Late-onset neurodegeneration in mice with increased dosage of the proteolipid
      protein gene.
AB  - Mutations of the proteolipid protein (Plp) gene cause a generalized central
      nervous system (CNS) myelin deficit in Pelizaeus-Merzbacher disease of man and
      various tremor syndromes in animal models. X-linked spastic paraplegia is also
      due to Plp gene mutations but has a different clinical profile and more
      restricted pathology involving specific tracts and regions. We have shown
      previously that PLP overexpression in mice homozygous for a Plp transgene results
      in premature arrest of CNS myelination and premature death. Here, we demonstrate
      that a low-level increase in Plp gene expression in transgenic mice causes
      significant axonal degeneration and demyelination with predilection for specific
      tracts. Following normal motor development, aged mice develop progressive myelin
      loss, axonal swellings with resultant Wallerian degeneration, and marked
      vacuolation of the neuropil associated with ataxia, tremor, and seizures. The age
      of onset and severity of the phenotype is a function of Plp gene dosage. The
      corticospinal tracts, optic nerve, fasciculus gracilis cerebellum, and brainstem
      are particularly involved. Although oligodendrocyte cell bodies show little
      abnormality, their inner adaxonal tongue is often abnormal, suggesting a
      perturbation of the axon/glial interface that may underlie the axonal changes. We
      conclude that abnormal expression of an oligodendrocyte-specific gene can cause
      axonal damage, a finding that is relevant to the pathogenesis of PLP-associated
      disorders and probably to other myelin-related diseases.

PMID- 9590559
TI  - Neocortex in the hippocampus: an anatomical and functional study of CA1
      heterotopias after prenatal treatment with methylazoxymethanol in rats.
AB  - Migration disorders cause neurons to differentiate in an abnormal heterotopic
      position. Although significant insights have been gained into the etiology of
      these disorders, very little is known about the anatomy of heterotopias. We have
      studied heterotopic masses arising in the hippocampal CA1 region after prenatal
      treatment with methylazoxymethanol (MAM) in rats. Heterotopic cells were
      phenotypically similar to neocortical supragranular neurons and exhibited the
      same temporal profile of migration and neurogenesis. However, they did not
      express molecules characteristic of CA1 neurons such as the limbic-associated
      membrane protein. Horseradish peroxidase injections in heterotopia demonstrated
      labeled fibers not only in the neocortex and white matter but also in the CA1
      stratum radiatum and stratum lacunosum. To study the pathophysiological
      consequences of this connectivity, we compared the effects of neocortical and
      limbic seizures on the expression of Fos protein and on cell death in MAM
      animals. After metrazol-induced seizures, Fos-positive cells were present in CA1
      heterotopias, the only hippocampal region to be activated with the neocortex. By
      contrast, kainic acid-induced seizures caused a prominent delayed cell death in
      limbic regions and in CA1 heterotopias. Together, these results suggest that
      neocortical heterotopias in the CA1 region are integrated in both the hippocampal
      and neocortical circuitry.

PMID- 9590560
TI  - Protective role of glutathione synthesis on radiation-induced DNA damage in
      rabbit brain.
AB  - 1. Radiotherapy has attracted increasing interest in recent years. It is known
      that ionizing radiation induces oxygen radical injury, whereas oxidative stress
      by the radiation can cause cellular responses to defense cellular injury. In this
      study, the metabolism of antioxidants in response to ionizing radiation to the
      brain was studied in the brain using experimental rabbits. 2. Ionizing radiation
      to the hemicerebrum caused an increase in the levels of glutathione (GSH) and the
      activity of a GSH synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma
      GCS), and Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Ionizing radiation also induced
      DNA-damage estimated by the formation of 8-hydroxydeoxyguanosine. These changes
      were dependent on the radiation dose. 3. Previous intrathecal-administration of
      buthionine sulfoximine (100 microM), a specific inhibitor of gamma-GCS, increased
      DNA damage by radiation in the radiated hemicerebrum. That of S-methyl GSH, on
      the other hand, resulted in a significant reduction of DNA damage by radiation.
      4. These results suggest that synthesis of GSH and Cu,Zn-SOD is responsive to
      ionizing radiation and this induction of antioxidants may play a role in reducing
      tissue damage in radiotherapy.

PMID- 9590562
TI  - Nerve-dependent factors regulating transcript levels of glycogen phosphorylase in
      skeletal muscle.
AB  - 1. Muscle glycogen phosphorylase (MGP), the rate-limiting enzyme for glycogen
      metabolism in skeletal muscle, is neurally regulated. Steady-state transcript
      levels of the skeletal muscle isozyme of MGP decrease significantly following
      muscle denervation and after prolonged muscle inactivity with an intact motor
      nerve. These data suggest that muscle activity has an important influence on MGP
      gene expression. The evidence to this point, however, does not preclude the
      possibility that MGP is also regulated by motor neuron-derived trophic factors.
      This study attempts to distinguish between regulation provided by nerve-evoked
      muscle contractile activity and that provided by the delivery of neurotrophic
      factors. 2. Steady-state MGP transcript levels were determined in rat tibialis
      anterior (TA) muscles following controlled interventions aimed at separating the
      contributions of contractile activity from axonally transported trophic factors.
      The innervated TA was rendered inactive by daily epineural injections of
      tetrodotoxin (TTX) into the sciatic nerve. Sustained inhibition of axonal
      transport was accomplished by applying one of three different concentrations of
      the antimicrotubule agent, vinblastine (VIN), to the proximal sciatic nerve for 1
      hr. The axonal transport of acetylcholinesterase (AChE) was assessed 7, 14, and
      28 days after the single application of VIN. 3. MGP transcript levels normalized
      to total RNA were reduced by 67% in rat TA, 7 days after nerve section. Daily
      injection of 2 microg TTX into the sciatic nerve for 7 days eliminated muscle
      contractile activity and reduced MGP transcript levels by 60%. 4. A single, 1-hr
      application of 0.10% (w/v) VIN to the sciatic nerve reduced axonal transport but
      did not alter MGP transcript levels in the associated TA, 7 days after treatment.
      Application of 0.10% VIN to the sciatic nerve also did not affect IA sensory or
      motor nerve conduction velocities or TA contractile function. 5. Treatment of the
      sciatic nerve with 0.40% (w/v) VIN for 1 hr reduced axonal transport and
      decreased MGP transcript levels by 50% within 7 days, but also reduced sensory
      and motor nerve conduction velocities and depressed TA contractile function. 6.
      Myogenin, a member of a family of regulatory factors shown to influence the
      transcription of many muscle genes, including MGP, was used as a molecular marker
      for muscle inactivity. Myogenin transcript levels were increased following
      denervation and after treatment with TTX or 0.40% VIN but not after treatment
      with 0.10% VIN. 7. The results suggest that MGP transcript levels in TA are
      regulated predominantly by muscle activity, rather than by the delivery of
      neurotrophic factors. Intrinsic myogenic factors, however, also play a role in
      MGP expression, since denervation did not reduce MGP transcript levels below 30%
      of control TA. The dominant influence of activity in the regulation of MGP
      contrasts with the proposed regulation of oxidative enzyme expression, which
      appears to depend on both activity and trophic factor influences.

PMID- 9590563
TI  - Differential expression of c-fos mRNA and Fos protein in the rat brain after
      restraint stress or pentylenetetrazol-induced seizures.
AB  - 1. c-fos mRNA expression and Fos protein expression were investigated by in situ
      hybridization and immunohistochemistry after 30 min of forced restraint stress or
      pentylenetetrazol (PTZ; 64 mg/kg, i.p.)-induced seizures. 2. Forced restraint
      stress and PTZ-induced seizures generated c-fos mRNA expression of distinct
      intensities, but in similar brain regions, including the hippocampus, the
      amygdala, the piriform cortex, the paraventricular hypothalamic nucleus, the
      habenula, and parts of the cerebral cortex. 3. The distribution of Fos-like
      immunoreactivity induced by stress or seizures only partially overlap. No Fos
      like expression was found in the hippocampus or the habenula after restraint
      stress. Nevertheless, both areas presented Fos-like expression after PTZ-induced
      seizures. 4. Our results support the suggestion that immediate early gene
      expression in vivo may exhibit both region- and stimulus-specific expression.

PMID- 9590561
TI  - Nicotine is more efficient than cotinine at passing the blood-brain barrier in
      rats.
AB  - 1. Nicotine and its main metabolite, cotinine, were reported to have distinct
      behavioral activities in mammals. 2. In this study, cotinine was synthesized
      without detectable nicotine contamination to compare the ability of nicotine and
      cotinine to pass the blood-brain barrier (BBB) in rats. 3. The alkaloids were
      extracted from plasma and brain tissues by methanol, identified by thin-layer
      chromatography, and quantified by high-pressure liquid chromatography and
      radioimmunoassays. 4. Consistently, the three methods showed that the passage of
      cotinine was time, route of administration, and dose dependent and that nicotine
      was more efficient than cotinine to pass the BBB. 5. The results suggest that
      these alkaloids may have central activities that probably result from their
      actions at distinct molecular levels.

PMID- 9590564
TI  - Characterization of the human dopamine transporter heterologously expressed in
      BHK-21 cells.
AB  - 1. cDNA of the human dopamine transporter (hDAT) was cloned into a cloning vector
      based on the Semliki Forest virus. Electroporation of in vitro transcribed mRNA
      from this plasmid into BHK-21 cells resulted in production of the transporter as
      measured by [3H]dopamine uptake (Km = 2.0 +/- 0.4 microM), which was specifically
      inhibited in the presence of cocaine. 2. The recombinant transporter protein
      exhibited an apparent molecular mass of 56 kDa, which was reduced to 50 kDa after
      tunicamycin treatment of the producing BHK-21 cells. Tunicamycin treatment of the
      electroporated cells also resulted in a decrease in transport activity with no
      change in the Km value (2.1 +/- 0.4 microM). 3. The localization of the
      heterologously produced transporter in the BHK cells either with or without
      tunicamycin treatment was studied by electron microscopic immunogold staining.
      The glycosylated transporter was found to be localized at the plasma membrane,
      whereas in the case of the unglycosylated transporter, transport to the plasma
      membrane was blocked.

PMID- 9590565
TI  - Distribution of the parathyroid hormone-related peptide and its receptor in the
      saccus vasculosus and choroid plexus in the red stingray (Dasyatis akajei:
      Elasmobranch).
AB  - 1. The exact role of the parathyroid hormone-related peptide (PTHrP) is not fully
      understood. We used immunohistochemistry to localize the PTHrP and its receptor
      in the brain of the red stingray, particularly in the saccus vasculosus (SV) and
      choroid plexus. 2. Immunoreactive PTHrP and its receptor were detected in the
      epithelial cells of the SV and the choroid plexus. In addition, the neuronal
      perikarya in the nucleus of the SV located in the hypothalamus is positive for
      the PTHrP. 3. No PTHrP-containing neurons were detected in the choroid plexus.
      Extracts of SV and choroid plexus showed positive reactions against the PTHrP and
      its receptor antibody in Western blot analysis. 4. High levels of immunoreactive
      PTHrP were detected in the plasma equivalent to those present in human humoral
      malignant hypercalcemia. In contrast, the immunoreactive PTHrP concentration in
      the cerebrospinal fluid was below detectable levels. 5. Our results suggest that
      the regulation of the PTHrP in the SV differs from that in the choroid plexus in
      the red stingray.

PMID- 9590566
TI  - Insulin as a vascular hormone: implications for the pathophysiology of
      cardiovascular disease.
AB  - 1. Metabolic disorders, such as obesity and non-insulin-dependent diabetes
      mellitus, and cardiovascular disorders, such as essential hypertension,
      congestive cardiac failure and atherosclerosis, have two features in common,
      namely relative resistance to insulin-mediated glucose uptake and vascular
      endothelial dysfunction. 2. Significant increases in limb blood flow occur in
      response to systemic hyperinsulinaemia, although there is marked variation in the
      results due to a number of confounding factors, including activation of the
      sympathetic nervous system. Local hyperinsulinaemia has a less marked vasodilator
      action despite similar plasma concentrations, but this can be augmented by co
      infusing D-glucose. 3. Insulin may stimulate endothelial nitric oxide production
      or may act directly on vascular smooth muscle via stimulation of the Na+-H+
      exchanger and Na+/K+-ATPase, leading to hyperpolarization of the cell membrane
      and consequent closure of voltage-gated Ca2+ channels. 4. There is evidence both
      for and against the existence of a functional relationship between insulin
      mediated glucose uptake (insulin sensitivity) and insulin-mediated vasodilation
      (which can be regarded as a surrogate measure for endothelial function). 5. If
      substrate delivery is the rate-limiting step for insulin-mediated glucose uptake
      (in other words, if skeletal muscle blood flow is a determinant of glucose
      uptake), then endothelial dysfunction, resulting in a relative inability of
      mediators, including insulin, to stimulate muscle blood flow, may be the
      underlying mechanism accounting for the association of atherosclerosis and other
      cardiovascular disorders with insulin resistance. 6. Glucose uptake may determine
      peripheral blood flow via stimulation of ATP-dependent ion pumps with consequent
      vasorelaxation. 7. A 'third factor' may cause both insulin resistance and
      endothelial dysfunction in cardiovascular disease. Candidates include skeletal
      muscle fibre type and capillary density, distribution of adiposity and endogenous
      corticosteroid production. 8. A complex interaction between endothelial
      dysfunction, abnormal skeletal muscle blood flow and reduced insulin-mediated
      glucose uptake may be central to the link between insulin resistance, blood
      pressure, impaired glucose tolerance and the risk of cardiovascular disease. An
      understanding of the primary mechanisms resulting in these phenotypes may reveal
      new therapeutic targets in metabolic and cardiovascular disease.

PMID- 9590567
TI  - Allosteric interactions at muscarinic cholinoceptors.
AB  - 1. An allosteric interaction occurs when the binding of a ligand to its site on a
      receptor is able to modify the binding of another ligand to a topographically
      distinct site on the same receptor and vice versa. The muscarinic cholinoceptors
      represent the best-studied examples of allosteric phenomena among the G-protein
      coupled receptor superfamily. 2. The simplest model describing allosteric
      interactions at muscarinic cholinoceptors is the ternary complex model, which
      allows for a three-way interaction between the receptor, a classical
      (orthosteric) ligand and an allosteric modulator. The interaction may be
      quantified using the dissociation constant of each ligand for its respective
      binding site on the free receptor and the 'co-operativity factor' alpha. This
      latter term is the ratio of affinities of a ligand for the occupied versus the
      unoccupied receptor and is a measure of the magnitude of the cooperativity
      between two concomitantly bound ligands. 3. Identification of allosteric
      phenomena requires the utilization of both radioligand binding and functional
      approaches. Manifestations of allosterism include: (i) a limited ability to
      influence radioligand binding as the concentration of the latter is increased;
      (ii) alterations in the dissociation rate of orthosteric ligands; (iii)
      curvilinear Schild regressions; and (iv) nonadditivity of agonist/orthosteric
      antagonist/allosteric modulator combination concentration ratios. 4. Allosteric
      modulators of muscarinic cholinoceptors represent a diverse range of compounds.
      Some of the most studied agents include gallamine, alcuronium and the bis
      ammonium compounds, C7/3'-phth and W84. Alcuronium has proven a most useful
      pharmacological tool, as it has been shown to display both positive and negative
      co-operativity, depending on the receptor subtype and orthosteric ligand involved
      in the interaction. 5. Evidence has accumulated pointing to the existence of a
      common allosteric binding site on the muscarinic cholinoceptors, located close to
      the orthosteric site, but at a more extracellular level. However, the possibility
      of more than one accessory binding site on various receptor subtypes cannot be
      excluded. 6. Allosteric modulators offer a number of potential therapeutic
      advantages, including a ceiling level to their effects and the possibility of
      'absolute selectivity' of action, based on the degree of co-operativity rather
      than the affinity of the modulator for any one receptor subtype.

PMID- 9590568
TI  - Poisoning and epidemiology: 'toxicoepidemiology'.
AB  - 1. There is little hypothesis-testing clinical research performed in toxicology.
      Randomized clinical trials are rare and most observational studies are performed
      on highly selected patients and are subject to marked bias. Thus, for many
      poisonings, our approach has been based almost entirely on deduction from known
      pharmacological/toxicological effects, generalizations from drugs within the same
      therapeutic class, animal data and case reports. This is also far from
      satisfactory, as many toxicological mechanisms are poorly understood and not
      related to the therapeutic class. 2. Although we need much better data to address
      the clinical and public health aspects of poisoning, there are many practical and
      ethical reasons why randomized clinical trials are difficult in this field.
      However, the scope for observational research, in particular population-based
      clinical epidemiology, is almost unlimited. The collection of data on human
      poisoning is facilitated because most non-fatal overdoses are admitted to
      hospital and by legal requirements to report to the coroner deaths that are due
      to poisoning. In the present article I argue that 'toxicoepidemiology', meaning
      the application of epidemiological methods to the problem of acute poisoning, is
      the best means we have of addressing deficiencies in our knowledge of poisoning.
      3. Examples are given of a variety of observational research strategies, ranging
      from audit to meta-analysis, that may be applied to clinical toxicology. From
      coronial and clinical data obtained from reasonably well-defined populations, it
      has been possible to identify a number of previously unrecognized differences in
      the severity and spectrum of toxicity between and within drug classes. Also, the
      demographic risk factors for poisoning and the reproducibility, validity and
      optimal use of diagnostic and therapeutic interventions can be assessed. 4. The
      major limitations to the range of associations and interventions that may be
      studied are the need to achieve adequate power to study uncommon outcomes or
      poisonings and the ability to replicate findings at other centres using similar
      methodology. The expansion of data collection to other centres has the potential
      largely to overcome these obstacles.

PMID- 9590569
TI  - Cosegregation of the Tnfalpha locus with cardiovascular phenotypes in the F2
      generation of a New Zealand genetically hypertensive and Brown Norway cross.
AB  - 1. The association of the Tnfalpha locus with several cardiovascular phenotypes
      and body mass has been studied in the F2 generation of a reciprocal cross between
      rats of the New Zealand genetically hypertensive (GH) and the normotensive Brown
      Norway (BN) strains. In the total F2 population the GH allele of Tnfalpha
      cosegregated with increased intra-arterial blood pressure (BP) in a recessive
      manner. A similar but weaker effect was observed for tail BP. 2. An association
      between genotype and body mass in females with GH grandfathers was also detected.
      3. An association between genotype and pulse rate was observed for females. 4.
      This work supports other evidence pointing to an association of a gene (or genes)
      on rat chromosome 20 with hypertension.

PMID- 9590571
TI  - Enhanced sensitivity of medullary depressor neurons to N-methyl-D-aspartate
      glycine site antagonists in the spontaneously hypertensive rat.
AB  - 1. The effects of the specific N-methyl-D-aspartate (NMDA)-glycine site
      antagonist 5-fluoro indole-2-carboxylic acid (FICA) and NMDA, microinjected into
      the vasodepressor caudal ventrolateral medulla, were compared in spontaneously
      hypertensive rats (SHR) and in Wistar-Kyoto (WKY) rats. 2. 5-Fluoro indole-2
      carboxylic acid elicited a significant pressor response (+20.0 +/- 4.9 mmHg) in
      SHR, but no change was found in the basal blood pressure of WKY rats. 3. The
      depressor response due to NMDA microinjection was significantly larger in SHR (
      48.0 +/- 4 mmHg) than in WKY rats (-23.0 +/- 1.9 mmHg). 4. Pre-injection of FICA
      attenuated the depressor effects of NMDA significantly, this blockade being
      significantly more pronounced in SHR (37.0 +/- 2.7 mmHg) than in WKY rats (12.0
      +/- 1.2 mmHg). 5. The enhanced responses to FICA may reflect the lower levels of
      the endogenous NMDA-glycine antagonist kynurenic acid in SHR compared with WKY
      rats.

PMID- 9590570
TI  - Absence of detectable regression of human hypertensive left ventricular
      hypertrophy following drug treatment for 1 year.
AB  - 1. The present study was designed to compare and contrast the effects of 1 year's
      treatment with angiotensin-converting enzyme inhibition (captopril 25-100 mg
      daily) and beta-blockade (atenolol 50-100 mg daily) on hypertensive cardiac
      structure and function as well as the other established cardiovascular risk
      factors of high blood pressure (BP), lipid profile and blood glucose. 2. This was
      a prospective randomized open drug trial with blinded end-point echocardiographic
      and cardiac Doppler assessment in 37 subjects who had primary essential
      hypertension and left ventricular hypertrophy of captopril (n = 20) versus
      atenolol (n = 17), adding hydrochlorothiazide if BP was not controlled by 1
      month. Multiple time point measurements throughout the 1 year treatment period of
      the study were made of BP, echocardiographic parameters of cardiac structure and
      function, as well as lipid profile and blood glucose. 3. There were no
      significant between-group differences for captopril or atenolol with regard to BP
      (at baseline (mean +/- SD) 154.0/101.1 +/- 13.3/5.1 and 152.5/101.8 +/- 10.0/5.8
      mmHg, respectively) which was normalized by 1 month (138.7/85.6 +/- 18.8/11.7 and
      135.4/88.5 +/- 16.9/9.5 mmHg, respectively) in both treatment groups (both P <
      0.01 vs baseline). Also, there were no between-group or within-group differences
      for any of the measures of left ventricular hypertrophy or systolic function
      throughout the 12 month treatment period; however, captopril alone significantly
      increased left ventricular early diastolic filling (P < 0.05 vs baseline) at most
      of the measured time points. Furthermore, there were no significant between- or
      within-group differences with regard to metabolic (lipids and glucose) profile
      over the 1 year treatment period of the present study. 4. Markers of
      cardiovascular risk, including BP, echocardiographic measures of left ventricular
      hypertrophy, lipid profile and blood glucose were not significantly different
      between therapies. Despite good BP control by 1 month, neither drug regimen
      regressed left ventricular hypertrophy. However, captopril significantly
      increased left ventricular early diastolic filling after 3 months of treatment.

PMID- 9590572
TI  - Sodium balance and jejunal ion and water absorption in Dahl salt-sensitive and
      salt-resistant rats.
AB  - 1. Apparent Na+ absorption and jejunal water, Na+, Cl- and K+ absorption in vivo
      was evaluated in young (prepubertal) and adult Dahl salt-sensitive (DS) and Dahl
      salt-resistant (DR) rats kept on a low-salt (low-salt rat chow + distilled water)
      or a high-salt diet (HS1 diet: NaCl-enriched rat chow + distilled water; HS2
      diet: standard rat chow + 1% saline as drinking fluid). These two high-salt diets
      were chosen because the HS1 regimen has been shown to increase blood pressure
      (BP) in DS rats and the HS2 regimen decreases jejunal water and ion absorption in
      normotensive Wistar rats. 2. The HS1 or HS2 diet increased BP in young and adult
      DS rats but had no effect on the BP of young and adult DR rats. 3. Irrespective
      of dietary Na+ intake, no significant difference of apparent Na+ absorption
      (dietary Na+ intake minus faecal Na+ output) was observed between DS and DR rats
      both in prepuberty and in adulthood. Young DS rats kept on a low-salt diet had
      increased faecal Na+ output in comparison with young DR rats. This difference
      disappeared with increasing dietary Na+ intake. 4. There were no interstrain
      differences on the effect of a high-salt diet on jejunal Na+ and K+ absorption in
      young and adult DS and DR rats. However, high-salt diets stimulated jejunal water
      and Cl- absorption in young DS rats, but not in adult DS rats and young and adult
      DR rats. Interstrain differences of water and Cl- absorption were observed only
      in adulthood. Adult DR rats kept on an HS2 diet absorbed more water and Cl- than
      their DS counterparts. 5. Our results do not indicate any abnormalities of
      apparent Na+ absorption and jejunal water and electrolyte transport in DS and DR
      rats. We conclude that there is no relationship between intestinal Na+ absorption
      and sensitivity or resistance to induction of experimental salt hypertension.

PMID- 9590573
TI  - Abolition of drug-induced early afterdepolarizations by potassium channel
      activators in guinea-pig Purkinje fibres.
AB  - 1. Drug-induced early afterdepolarizations (EAD) are considered to be the
      underlying mechanism of the polymorphic ventricular dysrhythmia torsades de
      pointes. Sotalol and disopyramide are well known to generate EAD. Therefore, it
      was of interest to study the effects of potassium channel activators, such as
      nicorandil, pinacidil and lemakalim, on those drug-induced EAD in spontaneously
      beating guinea-pig Purkinje fibres using the intracellular microelectrode
      technique. 2. Early afterdepolarizations induced by sotalol at concentrations of
      80 and 160 micromol/L could be completely abolished by nicorandil at
      concentrations between 50 and 500 micromol/L. The extracellular K+ concentration
      was 2.7 mmol/L. 3. Disopyramide-induced EAD at concentrations of 10, 20 and 30
      micromol/L in a Tyrode's solution containing 1.35 mmol/L K+ and these EAD were
      abolished by pinacidil (30 and 100 micromol/L) and lemakalim (10 and 30
      micromol/L). 4. Early afterdepolarizations could be regenerated by superfusion of
      Purkinje fibres with K+ channel activator-free Tyrode's solution containing
      either sotalol or disopyramide. 5. Our results demonstrate that drug-induced EAD
      can be abolished by K+ channel activators and, therefore, may provide anti
      arrhythmic effects in heart diseases.

PMID- 9590574
TI  - Effect of experimental diabetes mellitus on gentamicin-induced acute renal
      functional changes in the anaesthetized rat.
AB  - 1. Rats with streptozotocin (STZ) diabetes are protected from gentamicin (GEN)
      nephrotoxicity. Because the chronic renal damage from GEN is preceded by acute
      renal functional changes (notably hypercalciuria), the present study aims to
      determine whether diabetes may also protect against the acute effects of the
      drug. If there is a link between the rapid physiological actions of GEN and its
      subsequent nephrotoxicity, the former may also be affected by the diabetic
      condition. 2. Standard renal clearance techniques were performed on anaesthetized
      rats that had been injected with STZ or vehicle 2 weeks previously. All animals
      were infused with 0.9% NaCl for 5 h and then either GEN (0.28 mg/kg per min) or
      0.9% NaCl alone for 2 h. 3. Baseline fractional calcium excretion (FE(Ca)) of
      diabetic rats was three-fold that of control animals (6.6+/-0.2 vs 2.2+/-0.2%,
      respectively; P<0.01, MANOVA). Following GEN infusion, a comparable increase in
      FE(Ca) occurred in control and diabetic rats (5.3+/-0.6 vs 5.3+/-0.8%,
      respectively; NS). 4. Streptozotocin diabetes, therefore, does not alter the
      acute hypercalciuric response to GEN. This may suggest that the acute effects of
      GEN on renal calcium handling do not contribute to the subsequent nephrotoxicity.
      However, the higher baseline FE(Ca) seen in diabetic rats may afford protection
      against the renal injury caused by gentamicin.

PMID- 9590575
TI  - Chronic calcitonin administration and renal calcium transport in the rat.
AB  - 1. While calcitonin (CT) has now been clearly demonstrated to be a renal Ca2+
      conserving hormone and may share similar transport mechanisms with parathyroid
      hormone (PTH), the effect of prolonged CT exposure on renal Ca2+ transport has
      not been evaluated. 2. Consequently, a submaximal and maximal Ca2+-conserving
      concentration of human CT was infused into groups of anaesthetized acutely
      thyroparathyroidectomized rats that had been treated with twice daily
      subcutaneous human (h) CT at a low or high dose or vehicle for 12 days. 3. The
      maximal hCT infusion (10 microg bolus and per hour) produced a marked inhibitory
      effect on renal Ca2+ excretion in vehicle-treated rats, with the fractional
      excretion rate of Ca2+ being reduced from 4.49+/-0.31 to 139+/-0.23% (P<0.001).
      However, in rats pretreated with high concentrations of hormone (0.25 microg hCT)
      twice daily for 12 days, marked Ca2+ conservation was measured (fractional
      excretion 1.09+/-0.18%), which was not altered by the additional intravenous
      administration of maximal hCT. 4. Renal Mg2+ transport was similarly altered by
      hCT administration, without any evidence that prolonged CT inhibited renal Mg2+
      transport. The increase in glomerular filtration rate caused by hCT also appeared
      to persist with repeated hormone administration. The fractional excretion of Na+
      and PO4 was significantly increased by high- but not low-dose hCT treatment and
      was not altered by the addition of a maximal hormone dose at day 12. 5. The
      present study failed to demonstrate any down-regulation of the response to
      prolonged hCT administration when renal Ca2+ and Mg2+ transport was measured. If
      renal escape does occur with CT, as has been suggested but not proven with PTH,
      other mechanisms, such as hormone production or release, may be responsible.

PMID- 9590577
TI  - 5-Hydroxytryptamine-induced contraction of the marmoset aorta is mediated by a 5
      HT1-like receptor.
AB  - 1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the
      marmoset isolated aorta, actions that are unaffected by the 5-HT2 antagonist
      ketanserin. The aim of the present study was to define the receptors mediating
      the contractile activity of 5-HT in the marmoset aorta. 2. Contractile responses
      were elicited in aortic rings that were either: (i) precontracted submaximally
      with the thromboxane A2 agonist U44069 in order to amplify the responses; or (ii)
      exposed to N(omega)-nitro-L-arginine (100 micromol/L) plus LY 53857 (0.1
      micromol/L; a 5-HT2 receptor antagonist shown previously to inhibit relaxation).
      The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was
      also investigated. 3. The effects of agonists and antagonists comprised: (i)
      agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8
      hydroxy-2-(di-n-propylamino)tetralin; (ii) inhibition of contractile action of 5
      HT by the 5-HT1D antagonist GR 127935; (iii) a contractile response to
      methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT3 and 5
      HT4 receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT
      (in the presence of LY 53857), indicative of negative coupling to adenylate
      cyclase. 4. The above effects fulfill the criteria for a 5-HT1-like receptor. In
      view of the previous finding that this contractile response is insensitive to
      ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset
      aorta are mediated exclusively by a 5-HT1-like receptor.

PMID- 9590576
TI  - Dexamethasone-induced changes in endometrial growth and inducible nitric oxide
      synthase during decidualization in rats.
AB  - 1. The present study investigated the time-dependent inhibitory responses of
      endometrial growth and inducible nitric oxide synthase (iNOS) to dexamethasone
      during deciduoma development that was surgically induced on day 4 of
      pseudopregnancy (PG). 2. Groups of rats (n = 6) were subcutaneously injected with
      dexamethasone (1.5 mg/rat per day) for 3 days (PG days 1-3, 4-6, 7-9, 10-12 and
      12-15). Rats in each group were killed on the last injection day. 3.
      Dexamethasone produced comparable temporal inhibitory changes in endometrial
      growth (wet weight, protein and DNA concentrations; P<0.0001) and in iNOS
      activity (130 kDa protein band), which peaked after PG days 4-6 and 7-9
      pretreatments. 4. Endometrial matrix metalloproteinases (72 and 92 kDa) activity
      profiles displayed maximal reductions (36 and 53%, respectively) following PG
      days 4-6 pretreatment. Serum progesterone levels were equally (P<0.0001) but
      asynchronously inhibited by dexamethasone on PG days 9 and 12. 5. Dexamethasone
      inhibition of endometrial growth and in situ iNOS was most pronounced during
      decidual development (PG days 4-9). Minor reductions in these endometrial
      parameters occurred before deciduoma induction (PG days 1-3) and during deciduoma
      regression (PG days 10-15). 6. These results indicate that, in the endometrium,
      the iNOS/endogenous nitric oxide system may be linked to the biochemical and
      metabolic mechanisms responsible for the developmental responsiveness of the
      deciduoma to dexamethasone exposure. These time-dependent changes in endometrial
      growth and iNOS apparently were not mediated by progesterone.

PMID- 9590578
TI  - Angiotensin II receptors in cardiac left ventricles of Dahl rats.
AB  - 1. Dahl Iwai salt-sensitive (DS) rats have been reported as becoming hypertensive
      with left ventricular hypertrophy (LVH) and heart failure when on a high-salt
      diet. Their circulating renin-angiotensin system (RAS) has been reported to be
      suppressed. To evaluate the role of angiotensin II (AngII) type 1 and type 2
      receptors (AT1 and AT2, respectively) in LVH, we compared cardiac AT1 and AT2
      receptors in 10-week-old DS rats and Dahl Iwai salt-resistant (DR) rats. 2. Seven
      pairs of 6-week-old male DS and DR rats were fed either a low- or high-salt diet
      (0.3 or 8% NaCl, respectively) for 4 weeks. Left ventricular AngII receptors were
      measured by radioligand binding assays using [125I]-[Sar1,Ile8]-AngII in plasma
      membrane fractions from these four groups. The AT1 and AT2 receptors were
      distinguished using their specific antagonists CV 11974 and PD 123319,
      respectively. 3. The high-salt diet increased blood pressure and the left
      ventricle:bodyweight ratio in DS rats. However, neither Bmax for AT1 and AT2
      receptors nor Kd for [125I]-[Sar1,Ile8]-AngII differed between the groups. These
      results are different from those of other reports of pressure-overload LVH, such
      as spontaneously hypertensive rats or renovascular hypertension rats, in which
      AT1 and AT2 receptors were reported to be up-regulated.

PMID- 9590579
TI  - Different mechanisms for [Ca2+]i oscillations induced by carbachol and high
      concentrations of [Ca2+]o in the rat ventricular myocyte.
AB  - 1. The purpose of the present study was to explore the different mechanisms of
      [Ca2+]i oscillations induced by high concentrations of either carbachol (CCh) or
      extracellular Ca2+ ([Ca2+]o). First, we compared the oscillations induced by CCh
      at concentrations of 100-300 micromol/L and [Ca2+]o (5 mmol/L) in the single rat
      ventricular myocyte. Second, we studied CCh- and [Ca2+]o-induced [Ca2+]i
      oscillations following either interference with the production of inositol
      trisphosphate (IP3), reductions in cytosolic Ca2+ ([Ca2+]i), inhibition of Ca2+
      influx and Na+-Ca2+ exchange or depletion of Ca2+ from its intracellular store.
      2. The [Ca2+]i oscillations induced by CCh were frequent and were superimposed on
      [Ca2+]i transients in electrically stimulated cells, whereas those induced by
      high [Ca2+]o were occasional and occurred in quiescent cells and between [Ca2+]i
      transients in electrically stimulated cells. In both cases, [Ca2+]i oscillations
      were preceded by an increase in resting levels of [Ca2+]i. 3. Carbachol-induced
      [Ca2+]i oscillations were accompanied by an increase in amplitude and
      prolongation of the time of decline to 80% of the peak of the [Ca2+]i transient,
      while high [Ca2+]o-induced [Ca2+]i oscillations were the opposite. 4. A reduction
      of [Ca2+]o to 0.1 mmol/L and treatment with Ni2+ or ryanodine or 1,2-bis(2
      aminophenoxy)ethane-N,N,N', N'-tetraacetic acid AM (BAPTA-AM) abolished the
      [Ca2+]i oscillations induced by both CCh and high [Ca2+]o. 5. The calcium channel
      blockers verapamil and nifedipine and inhibitors of phospholipase C (neomycin and
      U-73122) abolished the [Ca2+]i oscillations induced by CCh; Li+ accelerated the
      onset of the [Ca2+]i oscillations induced by CCh. 6. These observations suggest
      that the mechanisms responsible for the [Ca2+]i oscillations induced by CCh and
      high [Ca2+]o are different from each other. Other than an increase in
      extracellular Ca2+ influx as a mechanism common for both CCh- and high [Ca2+]o
      induced [Ca2+]i oscillations, the CCh-induced [Ca2+]i oscillations involve influx
      of Ca2+ via L-type Ca2+ channels, Na+-Ca2+ exchange, mobilization of
      intracellular Ca2+ and IP3 production.

PMID- 9590580
TI  - Glucuronidation of dihydrocodeine by human liver microsomes and the effect of
      inhibitors.
AB  - 1. Glucuronidation is the major route of metabolism of dihydrocodeine (DHC) and
      accounts for 25-30% of an oral dose in urine. The kinetics of DHC-6-glucuronide
      formation in liver microsomes from five human donors and the effect of a number
      of potential inhibitor drugs were examined using a newly developed and validated
      HPLC assay. 2. The formation of DHC-6-glucuronide exhibited atypical kinetics
      that conformed to the Hill equation. The mean intrinsic dissociation constant
      (Ks) and maximum velocity (Vmax) values were 1566 micromol/L and 0.043
      micromol/min per g, respectively. The Ks and Vmax values varied 1.5- and 3.5
      fold, respectively. 3. Seven drugs were tested for inhibitory effects on DHC
      glucuronidation at low (50 micromol/L) and high (500 micromol/L) concentrations.
      At 50 micromol/L, only diclofenac produced greater than 50% inhibition, while at
      concentrations of 500 micromol/L inhibition was greater than 35% for diclofenac,
      amitriptyline, oxazepam, naproxen, chloramphenicol and probenecid, but not
      paracetamol. 4. The present study found little interindividual variation in the
      activity of human liver microsomes for glucuronidation of DHC. Comparison of the
      results from the inhibition studies with those reported previously for codeine
      and morphine suggest that the UDP-glucuronosyltransferase isoform UGT2B7 is
      involved in the glucuronidation of DHC.

PMID- 9590581
TI  - Experimental biology 1997 symposium on the role of integrins in acute renal
      failure.

PMID- 9590582
TI  - Epithelial cell shedding in acute renal injury.
AB  - 1. To address the postulate that sublethally injured tubular cells may be shed
      from renal epithelium while still viable, studies were undertaken in vivo in
      human 'acute tubular necrosis' and in rabbit models of renal tubular injury. 2.
      Substantial numbers of viable tubular cells were voided in the urine. When placed
      in culture, these cells gave rise to monolayers, confirming viability. The
      majority of intact cells demonstrated markers of proximal tubule. 3. In vitro
      studies of human renal proximal tubular cells exposed to hypoxia/anoxia showed
      rounding and retraction associated with disruption of actin microfilaments.
      Phalloidin stabilized the filaments and prevented the changes in cell shape
      indicative of altered adherence.

PMID- 9590583
TI  - Therapeutic effect of arginine-glycine-aspartic acid peptides in acute renal
      injury.
AB  - 1. Previous studies from our laboratory have suggested that arginine-glycine
      aspartic acid (RGD) peptides, serving as a decoy, may prevent tubular obstruction
      in the ischaemic model of acute renal failure. Specifically, we have demonstrated
      that: (i) stressed tubular epithelial cells reverse the polarity of integrin
      receptors from the predominantly basolateral location to the apical cell membrane
      as a part of a more generalized process of the loss of epithelial cell polarity;
      (ii) depletion of integrins expressed on the basal cell surface leads to the loss
      of anchorage to the basement membrane and cell desquamation; (iii) expression of
      integrin receptors on the apical cell membrane leads to indiscriminate
      interactions (e.g. the adhesion of desquamated cells to the cells remaining in
      situ), thus initiating the process of tubular obstruction; and (iv)
      conglomeration of the desquamated cells via integrin receptors further aggravates
      tubular obstruction. 2. Importantly, these integrin-based interactions can be
      blocked by synthetic RGD peptides. The linear RGD peptide injected into the renal
      artery upon release of the renal artery clamp prevented the elevation of proximal
      tubular hydrostatic pressure characteristically seen in animals with renal
      ischaemia that received injection of the vehicle of an inactive peptide. 3. In
      vivo study of RGD peptides in ischaemic acute renal failure in rats demonstrated
      attenuation of renal injury and accelerated recovery of renal function. 4. Using
      linear RGD peptide labelled with 99mTc; we have shown that this probe was
      retained in ischaemic kidneys. 5. To visualize RGD binding sites at the cellular
      level, we performed a mapping using fluorescent derivatives of two RGD peptides,
      a cyclic biotinylated (Bt)-RGD peptide and a linear Rhodamine green-labelled
      (RhoG)-RGD peptide. 6. The findings suggest that the binding sites for RGD
      peptide are represented by the alphaVbeta3 integrin in the vasculature and some
      desquamated cells, whereas the majority of the desquamated cells bind Bt-RGD via
      beta1 integrins. 7. These findings were further tested using cultured endothelial
      cells co-incubated with leucocytes. When co-incubation experiments were performed
      in the presence of cyclic RGD pentapeptide, the adhesion of HL-60 cells to both
      control and hypoxic endothelial monolayers was significantly reduced.

PMID- 9590584
TI  - Role of integrins in enterocyte migration.
AB  - 1. Enterocyte motility depends critically on cell-matrix interactions. Although
      still incompletely understood, these appear critically dependent upon integrin
      mediated cell adhesion. 2. In addition to providing a mechanism for cell adhesion
      and traction, the integrins are likely to serve as true receptors for the matrix
      across which cell motility occurs, initiating signals by both mechanical and
      chemical means that alter cell phenotype and proliferation as well as cell
      motility. 3. Sound rationale now exists to postulate that soluble growth factors
      within the extracellular milieu regulate intestinal mucosal healing not only
      directly but also indirectly by modulating integrin expression and organization.

PMID- 9590585
TI  - Leucocyte adhesion molecules in ischaemic renal injury: kidney specific
      paradigms?
AB  - 1. Renal ischaemic-reperfusion injury (IRI) is an important cause of acute renal
      failure in native kidneys and in allografts. 2. Leucocyte adhesion molecules
      CD11/CD18, intercellular adhesion molecule-1 and selectins mediate cardiac, skin
      and muscle IRI in experimental models and recent studies have begun to evaluate
      their role in renal IRI. 3. The CD11/CD18 has been shown to mediate renal IRI in
      rat models. 4. Intercellular adhesion molecule-1 has a more prominent role in
      mediating renal IRI than CD11/CD18 in both rat and mouse models. Blockade of both
      pathways together appears to provide synergistic protection. 5. Unlike in heart
      and muscle, L-selectin does not appear to mediate leucocyte recruitment to
      postischaemic kidney or tubular damage. 6. Leucocyte adhesion molecules may
      mediate renal IRI by mechanisms other than simply leucocyte migration, such as
      signal transduction and cell transport.

PMID- 9590586
TI  - Slime production by coagulase-negative staphylococci isolated in chronic
      blepharitis.
AB  - BACKGROUND: The purpose of the study was to determine the impact of slime
      producing strains of coagulase-negative staphylococci (CNS) on non-ulcerative
      blepharitis. Formerly considered harmless organisms, CNS are now recognised as
      opportunistic pathogens. Although these microorganisms are a component of normal
      conjunctival flora, they often produce the typical signs and symptoms of chronic
      staphylococcal blepharoconjunctivitis. Certain strains produce a polysaccharide
      extracellular material called "slime". Slime production is considered to be
      associated with the virulence of the organism. METHODS: Swabs were taken from the
      lids of 38 eyes of 19 patients with chronic non-ulcerative blepharitis and
      cultured for CNS. A group of 42 normal control eyes were similarly sampled. The
      strains of CNS isolated from 26 eyes (68.4%) of the patients with blepharitis and
      25 eyes (59.5%) of the normal subjects were studied for slime layer production.
      RESULTS: No significant difference was found between normal subjects and patients
      in the incidence of slime producing CNS strains from the conjunctiva. The
      antibiotic sensitivity profiles of the slime-producing strains were no different
      from the slime-negative isolates in the blepharitis (p=0.85) and normal group
      (p=0.25). CONCLUSIONS: Our data suggest that slime production by CNS does not
      play a significant role in the pathogenesis of staphylococcal blepharitis.

PMID- 9590587
TI  - Predictors of survival in malignant melanoma of the conjunctiva: a clinico
      pathological and follow-up study.
AB  - The study comprised 61 patients with histologically diagnosed malignant melanoma
      of the conjunctiva (MMC) who were treated and followed up in the Department of
      Ophthalmology, Clinical Center of Serbia, Belgrade, over a period of 24 years
      (1970-1993). Data on 15 clinical and 10 histopathological characteristics of MMC
      were related to the outcome of the disease. Tumour thickness on the histological
      section was the most important single predictor of survival in MMC. Other
      predictors of survival in MMC were the number of mitoses, the histologically
      assessed degree of tumour pigmentation and the intensity of inflammation at the
      tumour site. The variables entered into the model comprised as much as 85.3% of
      all predictors of survival in MMC.

PMID- 9590588
TI  - Non-freeze epikeratophakia in children.
AB  - We describe the use of unfrozen tissue lenses in 42 cases of epikeratophakia in
      children aged 2-14 years. Fourteen operations were performed in an aphakic eye,
      28 in combination with congenital or traumatic cataract extraction. The tissue
      lenses, made from unfrozen donor cornea according to an original design, healed
      in 91.5% of cases. The tissue lens was removed when epithelial growth was
      inadequate on its surface. A five-year follow-up showed that correction within
      3.0 D of emmetropia was achieved in 73.7% of the eyes. Preoperatively, mean
      keratometry readings were 43.5+/-0.2 D, increasing postoperatively to 53.6+/-0.8
      D. Mean spherical equivalent at the spectacle plane increased by 9.6+/-0.9 D. Our
      investigations show the efficacy and safety of non-freeze epikeratophakia in the
      correction of pediatric aphakia.

PMID- 9590589
TI  - Eyelid malpositions after cataract surgery.
AB  - PURPOSE: To estimate the incidence and the factors that may play a role in the
      etiology of eyelid malpositions after cataract extraction. METHODS: We followed
      up 124 patients for six months after cataract extraction. Palpebral aperture,
      levator function, height of the upper lid crease, lower eyelid laxity and
      position of the punctums were recorded preoperatively and postoperatively. Post
      cataract ptosis was defined as a 2 mm or greater drop in the lid margin after
      correcting for any change in the fellow eye. RESULTS: None of the patients
      developed ectropion or entropion, but five (4%) developed punctal ectropion after
      surgery. The incidence of post-cataract ptosis was 7.3% at six months. Age, sex,
      preoperative measurements of levator function, lid crease and dermatochalasis
      were not predictive for the development of ptosis at six months. However, there
      was a significant difference in the preoperative palpebral fissure width between
      the patients with ptosis and those without (p<0.05). There was a positive
      correlation between the mean volume of local anesthetic and the degree of ptosis
      on the first postoperative day (p<0.05, r: 0.1873). The presence and amount of
      ptosis on the first postoperative day was the best predictor of post-cataract
      ptosis at six months (p<0.001). CONCLUSIONS: Several factors are involved in the
      development of post-cataract ptosis. Temporary ptosis may be related to the
      myotoxicity of the local anesthetic. The presence of ptosis on the first
      postoperative day is the best predictor for the development of ptosis at six
      months.

PMID- 9590591
TI  - Optic disc measurements with the 78 diopter lens, Zeiss 4-mirror contact lens and
      computerized image analysing system.
AB  - We evaluated the 78 diopter (D) lens and Zeiss 4-mirror lens for the measurement
      of vertical and horizontal optic disc diameters during slit-lamp biomicroscopy
      and compared the results with the measurements made with the computerized image
      analysing system (IMAGEnet 640, Topcon, Japan) in 30 eyes of 30 patients. The 78D
      lens and Zeiss 4-mirror lens measurements both correlated well with the
      computerized image analysis measurements (r=0.881 for vertical and r=0.895 for
      horizontal disc diameter measurements with the 78D lens and r=0.883 for vertical
      and r=0.891 for horizontal disc diameter measurements with the Zeiss 4-mirror
      lens). The 78D lens measurements overestimated vertical disc diameter by 5.3% and
      horizontal disc diameter by 4.4%. The Zeiss 4-mirror lens underestimated the
      vertical disc diameter by 2.4% and horizontal disc diameter by 2.2%. Thus either
      lens can be used for a quick estimation of the optic disc size, since the results
      correlate well with the computerized image analysis measurements.

PMID- 9590590
TI  - The effects of Rimexolone 1% in postoperative inflammation after cataract
      extraction. A double-masked placebo-controlled study.
AB  - AIM: A multicentre, randomized, placebo-controlled double-masked study was
      conducted to assess the efficacy and safety of Rimexolone 1% eye drops in
      reducing inflammation after cataract surgery and intra-ocular lens implantation.
      METHODS: Rimexolone 1% (124 patients) or placebo (58 patients) was given, four
      times a day for 14 days starting 22-34 hours after surgery. All patients also
      received tobramycin 0.3% four times a day for 7 days. The clinical signs of
      ocular inflammation were recorded on days 1, 3, 8, 15 and 17 or 18. RESULTS:
      Rimexolone 1% markedly decreased the mean inflammation severity scores, and the
      sum of clinical assessments of cells and flare in the anterior chamber compared
      with placebo at each assessment. In addition, the percentage of patients with no
      anterior chamber inflammation was significantly higher with Rimexolone 1% than
      with the placebo at each assessment. All these results were statistically
      significant. Intra-ocular pressure did not rise after treatment with Rimexolone
      1%. CONCLUSIONS: The results suggest that Rimexolone 1% ophthalmic solution is an
      effective and safe steroidal anti-inflammatory agent for topical use following
      cataract surgery and intra-ocular lens implantation.

PMID- 9590592
TI  - Is the blind spot enlarged in early glaucoma?
AB  - PURPOSE: We investigated whether the blind spot is larger in early
      "preperimetric" glaucoma with already deeply excavated optic discs than in normal
      persons. METHODS: We examined eight eyes of five patients with definite
      glaucomatous optic disc cupping but normal visual fields. Ten eyes of five normal
      healthy volunteers, with normal central excavation, served as controls. With SLO
      perimetry we measured the differential light sensitivity 0.5-1.0 degrees outside
      the disc margins, "within" the center (Goldmann V stimulus) and along the
      horizontal meridian of the optic discs. Optic disc topography was documented with
      the Heidelberg Retina Tomograph (HRT). RESULTS: Differential light sensitivities
      adjacent to the optic discs did not differ in the two groups (normal 8.3dB, early
      glaucoma 8.4dB). Goldmann IV stimuli presented on the horizontal meridian of
      optic discs with glaucomatous cupping were seen up to 0.7 degrees centrally
      (i.e., towards the center) of the disc margin. In the control group this distance
      was significantly greater (1.3 degrees). The light differential thresholds with
      stimulus presentation in the disc center (Goldmann V) were significantly higher
      in the glaucoma group (0+/-2.8dB) than in the normal controls (6.6+/-1.3dB),
      though disc size was the same in both groups. CONCLUSIONS: Blind spots of normal
      discs seem to be smaller than those of deeply excavated discs in eyes with early
      glaucoma, possibly because there is more light scattering by the normal disc
      surface towards the adjacent functioning retina.

PMID- 9590593
TI  - The penetration of ofloxacin into human aqueous humor given by various routes.
AB  - This study was designed to measure the concentration of ofloxacin in aqueous
      humor after topical, oral and intravenous administration in 50 patients
      undergoing cataract extraction. In Group 1, ofloxacin 0.3% eyedrops were
      topically instilled ten times and the aqueous humor concentration was 2.73 +/-
      0.88 microg/ml. In Group 2, ofloxacin 0.3% eyedrops were topically instilled six
      times and the aqueous humor concentration was 0.84 +/- 0.61 microg/ml. Aqueous
      humor concentration 12 hours after 200 mg oral dose in Group 3, was 0.38 +/- 0.12
      microg/ml. In Group 4, patients were given ofloxacin as a single intravenous 200
      mg dose and the aqueous humor concentration 2 hours after the end of infusion was
      0.45 +/- 0.11 microg/ml. Concentrations were determined by high performance
      liquid chromatography (HPLC) with fluorescence detection. There was a significant
      difference between Group 1 and the other groups, but not between Group 2 and
      Groups 3, 4. It was concluded that ofloxacin penetrates the corneal and the blood
      aqueous barriers and can achieve good aqueous levels when given topically and
      systematically. Ofloxacin can be applied topically for external bacterial
      infections such as conjunctivitis and keratitis. Systematically administered
      ofloxacin reached higher levels than the MIC for some bacteria which cause
      endophthalmitis.

PMID- 9590594
TI  - In vitro effect of ascorbic acid on the proliferation of bovine scleral and
      Tenon's capsule fibroblasts.
AB  - The success of glaucoma filtration surgery depends mainly on an incomplete wound
      healing process in the area of the fistula. Since Kornblueth and Tenenbaum's
      investigations in 1956 it has been known that aqueous humour has intrinsic
      antiproliferative properties. It is assumed that ascorbic acid is involved in the
      regulation of the wound healing process after filtration surgery. To evaluate the
      antiproliferative effect of ascorbic acid in vitro, we used cultured fibroblasts
      of bovine Tenon's capsule and bovine sclera. Incubation of these cells with
      ascorbic acid at concentrations ranging from 0.5 to 3 mM/L led to dose-dependent
      inhibition of cell proliferation. The half-maximal inhibitory concentration was
      1.0 mM/L for both cell types. Physiological concentrations of ascorbic acid may
      be valuable in the pharmacological prevention of failure of glaucoma filtration
      surgery. However, extensive clinical investigations are needed to clarify whether
      topical intraoperative or postoperative as well as oral administration of
      ascorbic acid inhibits fibroblast proliferation after glaucoma filtration
      surgery.

PMID- 9590595
TI  - Central serous chorioretinopathy in two families.
AB  - PURPOSE AND METHODS: The reported occurrence of central serous chorioretinopathy
      (CSCR) in families is rare. We report two families (five patients) who have been
      diagnosed with CSCR. The diagnosis of CSCR was made on clinical and fluorescein
      angiographic findings. RESULTS: Three members of the first family and two members
      of the second family had CSCR. Affected individuals were all males. CONCLUSIONS:
      CSCR has been associated with psychological and emotional stress and the
      occurrence of CSCR in families may be due to similar inherited psychological and
      physiological characteristics and responses that predispose these families to the
      development of CSCR.

PMID- 9590596
TI  - Effect of sex in branch retinal vein occlusion.
AB  - PURPOSE: To evaluate the effect of sex in relation to crossing numbers, arterial
      overcrossings and occlusion sites in patients with branch retinal vein occlusion
      (BRVO). METHODS: Fifty-one eyes with BRVO (study group) and 48 eyes with retinal
      problems other than BRVO (control group) were investigated. All venous occlusions
      were examined in detail with regard to their anatomical positions, sites and
      arteriovenous crossings on the retinal surrounding area two disc diameters
      nasally, four disc diameters temporally, three disc diameters superiorly and
      three inferiorly from the optic disc, in the arteriovenous phase of fundus
      fluorescein angiography and fundus color photography. RESULTS: The study group
      comprised 29 women (56.86%) and 22 men (43.14%). All occlusions were unilateral
      and located at the crossing areas. BRVO had arterial overcrossing in 28 eyes
      (96.6%) in females and 22 eyes (95.5%) in males (p>0.005). The average numbers of
      crossings were 7.79 +/- 1.57 in females and 7.82 +/- 1.05 in males in the study
      group (p>0.05), and respectively 7.30 +/- 1.19 and 6.95 +/- 1.13 (p>0.05) in the
      control group. The average arterial overcrossing ratios were 75% in females and
      71% in males in the study group (p>0.05), and 74% and 65% in the control group
      (p<0.05). CONCLUSIONS: Our data suggest that females have a higher risk than
      males because of their arterial overcrossing ratio and BRVO prefer arterial
      overcrossing. However the insignificant difference between the female and male
      patients leads us to assume that the effect of sex on BRVO cannot be explained
      only by local anatomical factors since their effect is only slight.

PMID- 9590597
TI  - Air bag-associated retinal tear.
AB  - We report a case of a patient seen after a minor traffic accident, showing an
      ocular injury due to the air-bag, with minimal corneal edema and a retinal tear.
      When faced with the traumatic alterations caused by an inflated air-bag, we
      recommended detailed exploration of the peripheral retina.

PMID- 9590598
TI  - Cryptococcosis in Alabama.

PMID- 9590599
TI  - Surveillance of cryptococcosis in Alabama, 1992-1994.
AB  - PURPOSE: Although cryptococcosis is a significant opportunistic infection among
      patients with human immunodeficiency virus (HIV), there is conflicting
      information on rates of cryptococcosis among HIV-positive and HIV-negative
      patients. Precise state-wide epidemiologic data for cryptococcosis are not
      available in Alabama. METHODS: We conducted an active laboratory and hospital
      medical record-based surveillance for cryptococcosis in Alabama from October 1,
      1992 to September 30, 1994. A case of cryptococcosis was defined as a patient's
      initial episode of cryptococcal disease and based on either a positive culture
      for C. neoformans from any normally sterile site, a positive latex agglutination
      serologic test for cryptococcal antigen in CSF or serum, or histopathologic
      findings consistent with C. neoformans. RESULTS: Over the two year period, 153
      cases were identified. The diagnosis was based on positive culture (37%),
      positive antigen (24%), positive autopsy culture (2%), and histopathologic
      findings (4%). Further, 33% of the total cases were diagnosed from combined
      positive culture, antigen, or histopathology. Of the total 153 cases, 55% were in
      HIV-positive patients and 44% were in HIV-negative individuals and one case (1%)
      had an unknown HIV status. The overall annual incidence rate of cryptococcosis
      was 1.89 cases per 100,000 population. The incidence was 1638.7 per 100,000 in
      the HIV-positive population and 0.84 per 100,000 in the HIV-negative population.
      CONCLUSION: The first Alabama statewide active surveillance system for
      cryptococcosis confirms previous observations that rates of cryptococcosis are
      consistently higher in HIV-infected individuals than in their HIV-negative
      counterparts. In Alabama, cryptococcosis occurs more commonly in urban residents
      and in men. Cryptococcosis in HIV-positive persons is more likely to occur in the
      20 to 44 year age group, whereas cryptococcosis in HIV-negative persons is more
      likely to occur in those greater than 45 years old.

PMID- 9590600
TI  - Low dehydroepiandrosterone sulfate and heart disease in middle-aged men: cross
      sectional results from the Massachusetts Male Aging Study.
AB  - PURPOSE: Serum concentrations of the adrenal androgen dehydroepiandrosterone
      (DHEA) and its sulfate ester (DHEAS), both of which decline with age more
      markedly than other sex hormone levels, have been alternately credited and
      discredited as "protective" correlates of heart disease. Baseline data from the
      Massachusetts Male Aging Study (MMAS), collected in 1987-89, provided a large
      population-based random sample (n = 1709) in which to examine cross-sectionally
      the relation of DHEA and DHEAS levels to heart disease, while controlling for a
      comprehensive set of potential confounders including serum lipid and hormone
      levels as well as smoking, alcohol intake, obesity, hypertension, diabetes, diet,
      medication, physical activity, and psychological measures. METHODS: The subjects
      were men aged 40-70 years, randomly sampled from the Massachusetts state census
      listing, measured and interviewed at home. Nonfasting blood samples were assayed
      for hormones and lipids. RESULTS: In all strata of age, smoking, and alcohol
      intake, the age-adjusted odds ratio for self-reported heart disease was between
      0.55 and 0.85 per standard deviation (SD) of log DHEA and DHEAS concentration.
      Multiple logistic regression analysis indicated a strong independent role for
      DHEAS as a predictor of self-reported heart disease, controlling for age and the
      potential confounders listed above. The multiply-adjusted odds ratio for heart
      disease was 0.64 per SD log DHEAS concentration, with 95% confidence interval
      (CI) 0.50-0.83 (P = 0.0002). The DHEAS effect was not diminished by controlling
      for use of cardiac, vasodilator, antihypertensive, or lipid-lowering medication.
      CONCLUSIONS: These findings suggest that serum DHEAS levels bear an inverse
      relationship to heart disease, independently of a large set of established
      cardiovascular risk factors. The cross-sectional nature of this study requires
      that the findings be interpreted with caution.

PMID- 9590601
TI  - Age at natural menopause and mortality.
AB  - PURPOSE: The purpose of this study was to examine the association between age at
      menopause and mortality in a population-based sample of women in the United
      States. METHODS: This study was based on data from the National Health and
      Examination Survey (NHANES) Epidemiologic Follow-up Study; 3191 women aged 50-86
      years were included. There were 345 deaths over a mean follow-up time of 4.0
      years. We used age-stratified and Poisson regression procedures to assess
      mortality risk by age at natural menopause, with adjustment for age, duration of
      follow-up, race, education, smoking, and use of hormone replacement therapy. We
      conducted a separate analysis for surgical menopause with bilateral oophorectomy.
      RESULTS: Compared with women who were menstruating to age 50 or later, the
      adjusted mortality rate ratios (RR) were 1.50 (95% confidence interval (CI), 0.97
      2.34) for women with a natural menopause at age < 40, 1.04 (95% CI, 0.72-1.51)
      for those with menopause at age 40-44, and 0.96 (95% CI, 0.72-1.26) for those
      with menopause at age 45-49. Women with a natural menopause at age 40-44 years
      experienced an increased risk of cancer-related mortality (adjusted RR 2.34, 95%
      CI, 1.20-4.58). No age-related increased mortality risk was seen among women who
      had surgical menopause with bilateral oophorectomy. CONCLUSIONS: This study
      provides some support for the concept that age at natural menopause serves as a
      biological marker of health and aging, with potential implications extending
      beyond cardiovascular diseases.

PMID- 9590602
TI  - The relation of fasting insulin to blood pressure in a multiethnic population:
      the Miami Community Health Study.
AB  - PURPOSE: The aim of this study was to examine the associations among fasting
      insulin, adiposity, waist girth, and blood pressure among a nondiabetic
      multiethnic population. METHODS: A cross-sectional study was performed among 25
      44-year-old African-Americans (n = 159), Cuban-Americans (n = 128), and non
      Hispanic whites (n = 207) selected from Dade County, Florida. Fasting insulin
      levels were correlated with resting blood pressure level within each ethnic
      group. The separate effects of percentage body fat and waist girth on the
      association between blood pressure and insulin were analyzed in multiple linear
      regression and analysis of covariance. RESULTS: Fasting insulin was positively
      associated with systolic (r = 0.26-0.39; P < 0.01) and diastolic blood pressure
      (r = 0.19-0.30; P = 0.10 to P < 0.001) among women of all ethnic groups and among
      non-Hispanic white men (r = 0.27; P < 0.05). Stepwise linear regression analyses
      revealed statistically significant associations between systolic and diastolic
      blood pressure and fasting insulin level in non-Hispanic whites independent of
      other covariates, including sex and percentage body fat (P < 0.001). Fasting
      insulin was also independently and significantly related to systolic blood
      pressure among African-Americans (P = 0.02). Among Cuban-Americans, sex and
      percentage body fat were the main correlates of blood pressure level. Analysis of
      covariance revealed a relationship between insulin and blood pressure that was
      independent of waist girth among men and women. CONCLUSIONS: Fasting insulin
      level and blood pressure were positively associated among African-Americans and
      non-Hispanic whites. This association was not entirely due to the common
      association with percentage body fat or waist girth.

PMID- 9590603
TI  - Cancer and a fatiguing illness in Northern Nevada--a causal hypothesis.
AB  - PURPOSE: We investigated the possibility that chronic fatigue syndrome (CFS)
      predisposes to cancer by comparing the cancer pattern in an area in northern
      Nevada, where an outbreak of a fatiguing illness, which included cases of CFS,
      was reported, to an area in southern Nevada, where no such illness was reported.
      METHODS: Data from the computerized Nevada Cancer Registry were utilized to
      compare incidence rates of four malignancies--brain cancer, non-Hodgkin lymphoma
      (NHL), lung cancer, and breast cancer--in Washoe and Lyon Counties, where an
      unexplained fatiguing illness was reported during 1984-86, with comparably sized
      Clark County, where no such illness was reported. RESULTS: Higher incidences of
      NHL and primary brain tumors were noted in the two northern Nevada counties
      (Washoe and Lyon) in 1986 and 1987 respectively, compared to the southern Nevada
      (Clark) county. Similar patterns were not seen for breast or lung cancer.
      CONCLUSIONS: This study provides a model for investigating the possible
      predisposition of CFS patients to develop cancer using other cohorts, but it is
      currently premature to accept such a link at this time.

PMID- 9590605
TI  - The path analysis approach for the multivariate analysis of infant mortality
      data.
AB  - PURPOSE: This paper reviews the use of the Path Analysis (PA) methodology in
      health determinants modeling, with special reference to infant mortality
      modeling. METHODS: A review of the literature on PA applications in the modeling
      of infant mortality and similar problems is presented, together with a discussion
      of the conceptual basis of PA and its relation to other multivariate statistical
      techniques. Important aspects of the technique are discussed: 1) criteria for
      path formulation; 2) parameter estimation methods; 3) direct, indirect, spurious,
      and joint effects; and 4) goodness-of-fit and modification indices. RESULTS AND
      CONCLUSION: The review of the literature suggests that PA represents a
      methodological improvement regarding multivariate techniques used in modeling
      some health-related issues. PA allows investigation of more complex models,
      providing information that could have been previously overlooked, such as how the
      interrelations among independent variables in a model affect the dependent ones.

PMID- 9590604
TI  - Relations of hyperuricemia with the various components of the insulin resistance
      syndrome in young black and white adults: the CARDIA study. Coronary Artery Risk
      Development in Young Adults.
AB  - PURPOSE: To assess the association of hyperuricemia with the various components
      of the Insulin Resistance Syndrome (IRS) in a biracial cohort of young adults.
      METHODS: Cross-sectional study in 4053 young black and white adults aged 18-30
      years from the Coronary Artery Risk Development in Young Adults (CARDIA) study.
      RESULTS: Body mass index (BMI), fasting insulin, and triglycerides were
      significantly higher, and high density lipoprotein (HDL)-cholesterol lower in
      subjects with hyperuricemia (uric acid > or = 7.0 mg/dl in males; > or = 6.0
      mg/dl in females) (all p < 0.001). BMI showed the strongest positive correlation
      with uric acid among the IRS components. Significant associations of
      hyperuricemia with these risk factors were observed in all sex-race groups, which
      persisted after controlling for possible confounders including age, education,
      physical activity, smoking, alcohol intake, oral contraceptive use, and
      creatinine. Further adjustment for BMI and/or waist-to-hip ratio caused a large
      decrease in the strength of the associations. Adjustment for insulin also lead to
      decreases; however, the influence of fasting insulin appeared weaker than
      obesity. Even after controlling for obesity, insulin, and the other components of
      the IRS, male subjects in both races in the upper tertile of triglycerides were
      still more likely to have hyperuricemia. CONCLUSIONS: The association of
      hyperuricemia with most aspects of the IRS may result predominantly from their
      covariation with adiposity and secondarily with insulin level. Elevated
      triglyceride level seems to have an independent relationship with hyperuricemia
      in males. The relationship between hyperuricemia and cardiovascular disease
      observed in previous studies may be secondary to its association with the IRS.

PMID- 9590606
TI  - Measurement errors stemming from nonrespondents present at in-person interviews.
AB  - PURPOSE: Data are frequently collected from in-person interviews in epidemiologic
      studies. Despite the advantages of this mode of data collection, the presence of
      a third party during the interview can contribute to measurement error,
      especially if third-party presence is related to case status. METHODS: Using data
      obtained from a case-control study of colon cancer, we evaluated the frequency of
      third-party presence during in-person interviews, and how having someone else
      present during the interview influences reporting of exposure data. RESULTS:
      Interviews were conducted in the presence of a third party for 28% of cases and
      22% of controls who lived in a household of two or more individuals. Men with a
      third party present reported significantly lower age-adjusted mean levels of
      alcohol consumption (P < 0.01). Associations, as indicated by odds ratios,
      between colon cancer and alcohol intake were not statistically different among
      those with a third party present and those without a third party present.
      Although not statistically significant, energy intake was more strongly
      associated with colon cancer among those without a third party present during the
      interview. CONCLUSIONS: These results emphasize the need to review questions to
      be asked and decide whether privacy should be emphasized before data collection
      begins. If privacy is required, interviewers need to be given better skills to
      ensure privacy during interview.

PMID- 9590607
TI  - A census-based design for the recruitment of a community sample of older adults:
      efficacy and costs.
AB  - PURPOSE: This is a report of the scientific and cost implications of a census
      based design to identify residents aged 55 and over for a community study of the
      effects of aging on physical function. METHODS: A census of residents in a study
      community was conducted by the use of a mailed questionnaire. For households that
      did not complete and return the mailed census questionnaire, contact was
      attempted first by telephone and then by home visit. A comparison was made of the
      unit costs and characteristics of subjects identified by the different methods.
      RESULTS: A total of 3509 age-eligible subjects were identified (78.3% by mailer,
      19.5% by telephone, and 2.0% by home visit). Costs per enrolled age-eligible
      subject were lower for mailing and telephone ($7.76 and $4.72 respectively) than
      for home visit ($36.25). Subjects identified by home visit were significantly
      younger than subjects identified either by mail or telephone. After adjustment
      for age, subjects identified by telephone had less education and income and
      poorer health and functional status than subjects identified by mail. With the
      exception of age, there were no significant differences between subjects
      identified by mailer and home visit. CONCLUSIONS: A mailed questionnaire with
      telephone recontact is a practical strategy for community-based recruitment.
      Recontact of subjects by telephone can be expected to identify subjects who are
      not well-represented in a sample based only on a mailer. In contrast, the home
      visit is expensive and identifies subjects who do not differ meaningfully from
      those identified by mailer.

PMID- 9590608
TI  - Circulating mechanism of the "pure" venous flap: direct observation of
      microcirculation.
AB  - The circulating mechanism of the "pure" venous flap was studied via venography
      and direct observation of the microcirculation through transparent ear chambers
      and ear edges in a rabbit model. The flap, without arterial inflow, survived with
      normal hair growth and wound healing. Renewed blood circulation occurred 3 to 5
      hr after transfer There were two typical flow patterns in the venules: one was a
      shaking movement with high frequency and short range; the other was a pendulum
      like movement with low frequency and long range. The former was related to heart
      rate, while the later was not. The pendulum-like movement was the main flow
      responsible for perfusion of capillaries. Blood flow in the capillaries occurred
      1 to 2 hr later than that in the venules. The pendulum-like flow perfused the
      capillaries in two ways: one was in the direction of venules to capillaries and
      then back to venules along the same route; the other was from venules to
      arterioles through arteriovenous shunts and then to capillaries. The first type
      of perfusion was gradually replaced by the second 2 days after transfer. There
      were extensive venous plexus flows in the flap, which lasted more than 4 weeks
      after transfer. Revascularized vessels ultimately supplied blood to the flap. The
      dynamic energy for the movement of blood at an early post-transfer stage was
      probably due to spontaneous venomotion.

PMID- 9590609
TI  - Arterial changes following single-dose irradiation.
AB  - In this reported experiment, the serial morphologic changes in the rabbit ear
      central artery, following a single dose of 45 Gy 60Co gamma-ray irradiation, were
      investigated using light and scanning electron microscopy. Under light
      microscopy, mild intimal proliferation, disorganization of smooth muscle, and
      severe perivascular fibrosis were observed. These appeared to be caused by
      increased intimal cell death and lower repair capability after large single-dose
      irradiation. Under scanning electron microscopy, the endothelial cells did not
      show significant morphologic changes during the first 4 weeks. At 6 and 10 weeks
      after irradiation, the endothelial cells shrank in all directions and detached
      from the basement membrane. These changes accord with the theory that radiation
      damage following therapeutic dosage occurs within the DNA of the cell, and that
      there is no significant change until the cell attempts to divide.

PMID- 9590610
TI  - Occasions for multiple flaps in lower-limb reconstructions: once is sometimes not
      enough.
AB  - A retrospective review of 11 patients with complex and massive lower-limb defects
      requiring multiple transfers and/or regional muscle flaps for closure, found that
      microvascular transfers achieved final wound closure, either alone or in concert
      with local flaps, in all but one case. A local flap alone was not sufficient for
      any failed transfer reconstruction. This suggested that transfers are not only
      the best initial approach for massive lower-extremity defects, but they are
      sometimes the only solution available in complex lower-limb reconstruction, often
      when other options have failed.

PMID- 9590611
TI  - Effects of neurolysis during nerve regeneration: a behavioral and
      electrophysiologic study.
AB  - In closed injuries, nerves may be damaged by compression, stretch, or friction;
      the lesion may be circumscribed or extensive. Indications for exploratory surgery
      are very difficult to establish. However, in a number of cases, no lesions are
      observed during surgery and only neurolysis is performed. Neurolysis,
      nevertheless, may devascularize the nerves, compromising the final outcome of
      nerve regeneration. The goal of this reported work was to study the effects of
      neurolysis during the process of regeneration. Experiments were performed in the
      rat median nerve, and assessment was made by behavioral and electrophysiologic
      studies 2, 3, 6 and 12 weeks after surgery. The experiments demonstrated that
      exploratory microneurolysis had no deleterious effect on nerve recovery when
      performed during the process of nerve regeneration. Indeed, microneurolysis
      accelerated the rate of nerve recovery. Early exploratory surgery thus had no
      deleterious effects on nerve regeneration, and not only offered a better
      prognosis in reparable lesions, but also a potential beneficial effect of
      neurolysis in accelerating recovery.

PMID- 9590612
TI  - Microarchitecture and innervation of the human latissimus dorsi muscle.
AB  - Re-investigation of the adult human latissimus dorsi muscle (HLD) by
      microdissection of acetylcholinesterase (AChE)-stained material revealed a
      complicated microstructure of this muscle. Motor endplates distribute over the
      entire muscle; numerous AChE-stained myomyonal and myotendinous junctions are
      interspersed. After teasing muscle fascicles from selected representative areas,
      the following results were obtained. Most of the single muscle fibers
      constituting the fascicles are shorter than the length of the fascicles. They are
      linked together by myomyonal junctions or by myotendinous intersections end-to
      end, end-to-side, or via muscular crossbridges side-to-side, thus forming chains
      and nets of varying appearance and length. Additionally, many fiber furcations
      were found. These observations throw light on the microarchitectural basis of
      local mass changes of the triangular HLD occurring during its convergence from
      its wide lumbar and thoracic attachment line to its narrow tendon attached to the
      humeral crista tuberculi minoris. The microstructural observations also explain
      why motor endplates spread over the whole muscle, instead of being restricted to
      a single central endplate-band, as is found in the majority of other muscles. To
      clarify postnatal development, the topography of endplates in adult muscles was
      compared with fetal and infantile muscles. Primarily, the endplate bands were
      clearly demarcated; their width then broadened, and they gradually scattered into
      groups of single endplates. Simultaneous with these developmental changes, a
      corresponding branching of the thoracodorsal nerve occurs.

PMID- 9590613
TI  - Acute and chronic effects of nicotine on anastomotic patency following
      ischemia/reperfusion.
AB  - The effect of nicotine on anastomotic patency was studied using an isogenic rat
      knee transplantation model. Animals were divided into experimental and control
      groups, with experimental animals exposed to either 40 days of twice-daily
      nicotine injections (Group 1-chronic exposure) or acute nicotine exposure by
      graft perfusion (Group 2-acute exposure). Four and 6 hr warm ischemia times were
      studied. Syngeneic rat knees were transplanted from donor to recipient by
      microvascular anastomosis of the femoral vessels. There was a statistically
      significant difference (p < 0.05) in anastomotic patency after 4 hr of ischemia
      in Group 1 animals exposed to nicotine (33 percent patency) vs. controls (89
      percent patency). In addition, there was a statistically significant difference
      in anastomotic patency after 4 hr of ischemia in Group 2 animals exposed to
      nicotine (11 percent patency) vs. controls (67 percent patency). No significant
      differences between controls and Group 1 animals were noted in anastomotic
      patency after 6 hr of ischemia. Both acute and chronic nicotine exposure reduces
      anastomotic patency after short intervals of warm ischemia in vascularized
      composite tissue grafts. This detrimental effect is lost when the ischemic
      interval is prolonged to periods with poor anastomotic patency rates related to
      the ischemia/reperfusion itself.

PMID- 9590614
TI  - Vascularized bone grafts in the treatment of juxta-articular giant-cell tumors of
      the bone.
AB  - The clinical results of vascularized bone grafts in 39 patients with giant-cell
      tumor affecting the extremity were evaluated. The sites involved were the
      proximal tibia (8), proximal femur (4), calcaneus (1), proximal humerus (8), and
      distal radius (18). Osteoarticular replacement was performed in patients with
      giant-cell tumor involving the radius; in 15 of these, a suitably tailored
      vascularized iliac crest graft was used, and in the remaining three, the fibula
      was used. Follow-up ranged from 2 to 7 years, with an average of 3.3 years.
      Clinical results were judged on the basis of functional and radiologic
      evaluations. Reconstructions involving the distal radius were evaluated
      separately from the rest of the juxta-articular grafts. Excellent results in 17
      and good results in three of the juxta-articular grafts were observed. Eighteen
      patients with the distal radius affected were followed-up for periods ranging
      from 2 to 12 years. Non-union was seen in one, carpal subluxation in five, and
      spontaneous radiocarpal fusion in one patient. A pain-free functional wrist was
      retained in 17 of these 18 patients. Three local recurrences were observed (2.5
      percent). The vascularized bone graft provided a good biological and mechanical
      support to the subchondral bone and overlying articular cartilage. Satisfactory
      reconstruction was thus possible following wide resection, without sacrificing
      joint function and with gratifying oncologic results. The use of a suitably
      tailored block of vascularized iliac crest is an acceptable method to preserve
      wrist and radio-ulnar joint motion, following excision of the distal radius
      affected by a giant-cell neoplasm.

PMID- 9590615
TI  - Limb xenotransplantation using FK506 and RS61443 immunosuppression.
AB  - A new model of limb xenotransplantation has been developed to determine whether
      the newer immunosuppressive agents, FK-506 and RS-61443, either alone or in
      combination, can delay the rejection of a composite limb xenograft from donor
      Golden Syrian hamsters to recipient Lewis rats. Using a short-term course of
      immunosuppression for 14 days post-transplant, both FK-506 2 mg/kg/day and RS
      61443 30 mg/kg/day were able to delay rejection. FK-506-treated animals had a
      mean rejection time of 10.2 days and RS-61443-treated animals had a mean
      rejection time of 10 days, compared with a mean rejection time of 6.4 days in non
      immunosuppressed controls. Combination and sequential immunosuppression with both
      FK-506 and RS-61443 did not produce any improvement, compared with single-agent
      immunosuppression, and were quite toxic. Histologically, FK-506 seemed to prevent
      signs of rejection in the skin and muscle components of the limb xenograft better
      than RS-61443.

PMID- 9590616
TI  - The three-quarters vein anastomosis: a teaching tool for microsurgery.

PMID- 9590617
TI  - Microsurgical training with beads.
AB  - To assist beginners in the microsurgical practices of handling instruments and
      tying knots before using an animal model, the authors suggest the use of colored
      beads. These beads will diminish eyestrain and secondary fatigue. Also, working
      with colored beads might be a little more amusing and enjoyable for beginners in
      learning microsurgical techniques during preliminary studies to achieve the
      necessary orientation for working under the operating microscope.

PMID- 9590618
TI  - Use of the disposable stapler to insure proper fixation of a transferred muscle
      in treatment of facial paralysis.
AB  - The authors introduce the use of a disposable stapler to create a stable muscle
      end in transferring a free neurovascular muscle segment for the treatment of
      facial paralysis. This procedure allows the firm fixation of the fragile soft end
      of a muscle transferred to the nasolabial region of a paralyzed face, and avoids
      adhesion and tethering of the muscle end to the skin, which may result in
      inaccurate positioning of a newly-created nasolabial fold and an asymmetrical
      smile. Transection and hemostasis at both ends of the harvested muscle segment
      also can be achieved simultaneously. Although the disposable stapler incurs
      additional cost, it can greatly improve the result of a free neurovascular muscle
      transfer for the treatment of facial paralysis, as well as simplify harvesting of
      the muscle segment. No complications and problems have been encountered in
      stapling the muscle.

PMID- 9590619
TI  - Free vascularized fibular grafts for reconstruction of large femoral defects
      involving the knee joint: report of two cases.
AB  - Large femoral defects involving the knee joint have been successfully
      reconstructed using free vascularized fibular grafts and May anatomical bone
      plates. The operative technique and functional results are presented.

PMID- 9590620
TI  - Effect of ketorolac tromethamine (Toradol) on ischemia-reperfusion injury in
      skeletal muscle.
AB  - The eicosanoids, leukotriene B4 (LTB4) and thromboxane A2 (TXA2), contribute to
      neutrophil adhesion and arteriole vasoconstriction, important microcirculatory
      events in ischemia-reperfusion (I-R) injury. The purpose of this study was to
      evaluate the effect of ketorolac on I-R injury of skeletal muscle. A
      videomicroscopic preparation of gracilis muscle in male Wistar rats (n=7) in two
      experimental groups was evaluated: Group 1-4 hr global ischemia only (19
      arterioles, 19 venules), and Group 2-4 hr ischemia plus ketorolac (13 arterioles,
      14 venules). Ketorolac (0.86 mg/kg, i.m.) was given 30 min prior to reperfusion.
      The number of neutrophils, rolling and adherent, was counted in 100-micron
      venular segments, and arteriole diameters were measured at 5, 15, 30, 60 and 120
      min of reperfusion. The I-R-induced increase in neutrophil adhesion was
      significantly reduced by ketorolac, which significantly increased arteriolar
      vasodilation in the first 30 min of reperfusion and significantly reduced the I-R
      induced vasoconstriction in arterioles at 30 min; this effect was lost at 1 hr of
      reperfusion. Although ketorolac augments immediate arteriole vasodilation and
      blocks subsequent vasoconstriction, this effect appears to be transient. These
      findings suggest that ketorolac may have potential as a treatment for I-R injury.

PMID- 9590621
TI  - Gas chromatography-mass spectrometry methods for structural analysis of fatty
      acids.
AB  - Procedures for structural analysis of fatty acids are reviewed. The emphasis is
      on methods that involve gas chromatography-mass spectrometry and, in particular,
      the use of picolinyl ester and dimethyloxazoline derivatives. These should be
      considered as complementing each other, not simply as alternatives. However,
      additional derivatization procedures can be of value, including hydrogenation and
      deuteration, and preparation of dimethyl disulfide and 4-methyl-1,2,4-triazoline
      3,5-dione adducts. Sometimes complex mixtures must be separated into simpler
      fractions prior to analysis by gas chromatography-mass spectrometry. Silver ion
      and reversed-phase high-performance liquid chromatography are then of special
      value. In particular, a novel application of the latter technique, involving a
      base-deactivated stationary phase and acetonitrile as mobile phase, is described
      that is suited to the separation of fatty acids in the form of picolinyl ester
      and dimethyloxazoline derivatives, as well as methyl esters.

PMID- 9590622
TI  - Isolation and structure of a new galactolipid from oat seeds.
AB  - Seeds of oat (Avena sativa L.) were recently shown to contain significant
      quantities of a new hydroxy acid, (15 R)-hydroxy-(9Z),(12Z)-octadecadienoic acid
      (trivial name, avenoleic acid). In the present work, avenoleate was found to be
      mainly (63%) localized in the glycolipid fraction of oat seed lipids.
      Fractionation of the glycolipids by thin-layer chromatography and reversed-phase
      high-performance liquid chromatography revealed the presence of a main molecular
      species which accounted for 20% of the total avenoleate content of oat seeds.
      Structural studies by chemical methods and mass spectrometry demonstrated that
      the avenoleate-containing glycolipid was a galactolipid assembled of one molecule
      of avenoleic acid, two molecules of linoleic acid, two molecules of D-galactose,
      and one molecule of glycerol. Degradation of the new galactolipid by chemical and
      enzymatic methods demonstrated the localization of acyl chains, i.e., linoleate
      at sn-1 and linoleoylavenoleate at sn-2. Nuclear magnetic resonance spectroscopy
      gave independent support for this structure and also demonstrated that the two
      galactoses formed an alpha-D-galactopyranosyl-1-6-beta-D-galactopyranosyl moiety
      which was bound to the sn-3 position. Based on these experiments, the new
      galactolipid could be formulated as 1-[(9'Z),(12'Z)-octadecadienoyl]-2-[(15''R)
      [(9'''Z),(12'''Z)-o ctadecadienoyloxy]-(9''Z),(12''Z)-octadecadienoyl]-3-(alpha-D
      g alactopyranosyl-1-6-beta-D-galactopyranosyl)-glycerol. Quantitatively, the
      amount of the avenoleate-containing galactolipid was of the same order of
      magnitude as those of individual molecular species of digalactosyldiacylglycerol
      containing nonoxygenated acyl chains. The content of the new galactolipid in oat
      seeds was 0.5-0.6 mg per g of seed.

PMID- 9590623
TI  - Stoichiometric and kinetic studies on Ginkgo biloba extract and related
      antioxidants.
AB  - Owing to increasing evidence showing the importance of lipid peroxidation in
      oxidative stress in vivo, the role and evaluation of antioxidants have received
      much attention. Ginkgo biloba extract (GBE), well-known as an efficient drug
      against diseases induced by free radicals, has been suggested to exert its effect
      by antioxidant action. A method was established to determine the activity of GBE
      as a hydrogen donor by stoichiometric and kinetic studies, and GBE was compared
      with several other antioxidants such as alpha-tocopherol, propyl gallate, and two
      kinds of flavonoids which are found in GBE, quercetin, and kaempferol. It was
      found that there were 6.62 x 10(19) active hydrogens in 1 g of GBE.
      Stoichiometric studies showed that one molecule of alpha-tocopherol reacted with
      one molecule of galvinoxyl radical. For quercetin, kaempferol and propyl gallate,
      the experimental stoichiometric numbers were 4.0, 1.9, and 3.1, respectively. The
      rates of reaction of antioxidants with galvinoxyl in ethanol were determined
      spectrophotometrically, using a stopped-flow technique. The second-order rate
      constant, k2, obtained at 25 degrees C was 0.13 (g/L)(-1)s(-1) for GBE and 5.9 x
      10(3), 2.1 x 10(3), 1.2 x 10(4), and 2.4 x 10(3) M(-1)s(-1) for quercetin,
      kaempferol, propyl gallate, and alpha-tocopherol, respectively. The second-order
      rate constant, k2', on the molar basis of active hydroxyl groups in the tested
      substances obtained at 25 degrees C decreased in the order of propyl gallate >
      alpha-tocopherol > quercetin > GBE approximately kaempferol. This is the first
      study on GBE as an antioxidant which reports both stoichiometric and kinetic
      results.

PMID- 9590625
TI  - Biochemical and structural characterization of triacylglycerol lipase from
      Penicillium cyclopium.
AB  - An extracellular lipase, active on water-insoluble triacylglycerols, has been
      isolated from Penicillium cyclopium. The purified enzyme has a molecular mass of
      29 kDa by gel filtration and SDS-polyacrylamide gel electrophoresis. It
      hydrolyzes emulsions of tributyrin, trioctanoin, and olive oil at the same rate
      as pancreatic lipase and shows very low activity against partial acylglycerols
      (monooctanoin and dioctanoin) and methyl esters. It is stable at 35 degrees C for
      60 min and has maximal activity in a pH range of 8-10. Hydrolysis of
      triacylglycerols by P. cyclopium lipase is inhibited by detergents such as Triton
      X-100. Comparison of the sequence of the 20 first amino acid residues of P.
      cyclopium triacylglycerol lipase with other Penicillium lipases indicates a high
      homology with previously characterized lipases produced by P. expansum and P.
      solitum which are enzymes of comparable size and substrate specificity.
      Conversely, homology between P. cyclopium lipase and P. simplicissimum lipase, a
      nonspecific lipolytic enzyme, is low. Penicillium cyclopium triacylglycerol
      lipase shows no homology with P. camembertii lipase which is specific to
      monoacylglycerol and diacylglycerol.

PMID- 9590624
TI  - Lipid molecular order in liver mitochondrial outer membranes, and sensitivity of
      carnitine palmitoyltransferase I to malonyl-CoA.
AB  - Mitochondrial outer membranes were prepared from livers of rats that were in the
      normal fed state, starved for 48 h, or made diabetic by injection of
      streptozotocin. Membranes were also prepared from starved late-pregnant rats. The
      latter three conditions have previously been shown to induce varying degrees of
      desensitization of mitochondrial overt carnitine palmitoyltransferase (CPT I) to
      malonyl-CoA inhibition. We measured the fluorescence polarization anisotropy of
      two probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)
      6-phenyl-1,3,5-hexatriene-p-toluenes ulfonate (TMA-DPH) which, when incorporated
      into membranes, report on the hydrophobic core and on the peripheral regions of
      the bilayer, respectively. The corresponding polarization indices (rDPH and rTMA
      DPH) were calculated. In membranes of all three conditions characterized by CPT I
      desensitization to malonyl-CoA, rDPH was decreased, whereas there was no change
      in rTMA-DPH, indicating that CPT I is sensitive to changes in membrane core,
      rather than peripheral, lipid order. The major lipid components of the membranes
      were analyzed. Although significant changes with physiological state were
      observed, there was no consistent pattern of changes in gross lipid composition
      accompanying the changes to membrane fluidity and CPT I sensitivity to malonyl
      CoA. We conclude that CPT I kinetic characteristics are sensitive to changes in
      lipid composition that are localized to specific membrane microdomains.

PMID- 9590626
TI  - Enhanced macrophage uptake of lipoprotein(a) after Ca2+-induced aggregate
      formation.
AB  - We tested the hypothesis that aggregated lipoprotein(a) [Lp(a)] is avidly taken
      up by macrophages. Lp(a) was isolated by sequential centrifugations and gel
      chromatography from a patient with high plasma levels of Lp(a) who was being
      treated with low density lipoprotein (LDL)-apheresis. Aggregated Lp(a) was
      prepared by mixing native Lp(a) with 2.5 mmol/L CaCl2, and 54% of the 125I-Lp(a)
      aggregated after interacting with CaCl2. The binding and degradation of
      aggregated Lp(a) in macrophages were 4.6- and 4.7-fold higher than those of
      native Lp(a), respectively. An excess amount of LDL did not inhibit either
      increase. Cholesterol esterification in macrophages was markedly stimulated by
      aggregated Lp(a), and macrophages were transformed into foam cells. Cytochalasin
      B, a phagocytosis inhibitor, strongly inhibited the degradation and cholesterol
      esterification (78 and 83%, respectively). These findings suggested that
      aggregation may be partially involved in Lp(a) accumulation, thereby contributing
      to the acceleration of atherosclerosis.

PMID- 9590627
TI  - Effect of selenium and vitamin E supplements on tissue lipids, peroxides, and
      fatty acid distribution in experimental diabetes.
AB  - The protective role of selenium (Se), given as a Se-rich yeast, selenomethionine
      or selenomethionine + vitamin E supplement, toward changes in lipid, peroxide,
      and fatty acid distribution in tissues of streptozotocin-induced diabetic rats,
      was investigated, after 24 wk of disease. Diabetes increased liver thiobarbituric
      acid-reactive substances and conjugated dienes; Se supplement completely
      corrected these changes. In kidney, as in heart, the peroxide levels were not
      significantly changed by diabetes. In diabetic rat liver, a significant drop in
      triglycerides and phospholipids (P < 0.05) was observed; this was modulated by Se
      + vitamin E supplementation. Se + vitamin E supplementation also inhibited the
      decrease in 18:2n-6 and the increase in 22:6n-3 observed in liver of diabetic
      rats, changes which reflect altered glycemic control. In kidney, heart, and
      aorta, diabetes produced some changes in lipid content and fatty acid
      distribution, especially an increase in heart triglycerides which was also
      corrected by the Se supplement. Se supplementation to diabetic rats also
      increased 18:0 ether-linked alcohol, 20:4 n-6, and 22:5 n-3 in cardiac lipids. In
      aorta, Se + vitamin E significantly increased 20:5 n-3. These polyunsaturated
      fatty acids are precursors, in situ, of prostaglandin I2 (PGI2) and PGI3 which
      may protect against cardiovascular dysfunction. In kidney, conversely, Se
      decreased 20:4 n-6, the precursor of thromboxane A2 implicated in diabetic
      glomerular injury. Thus Se, and more efficiently Se + Vitamin E supplementation,
      in experimental diabetes could play a role in controlling oxidative status and
      altered lipid metabolism in liver, thereby maintaining favorable fatty acid
      distribution in the major tissues affected by diabetic complications.

PMID- 9590628
TI  - Chronic dietary n-3 polyunsaturated fatty acids deficiency affects the fatty acid
      composition of plasmenylethanolamine and phosphatidylethanolamine differently in
      rat frontal cortex, striatum, and cerebellum.
AB  - As chronic consumption of a diet devoid of n-3 fatty acid induced modification of
      neurotransmission pathways in the frontal cortex of rats, plasmalogen alteration
      could occur in this area. Because of the propensity to facilitate membrane
      fusion, plasmenylethanolamine (PmE), a major plasmalogen of brain, may be
      involved in synaptic transmission. Female rats were fed diet containing peanut
      oil [(n-3)-deficient diet] through two generations. Two weeks before mating, half
      of the female rats of the second generation received a diet containing peanut oil
      and rapeseed oil (control group). The distribution and acyl composition of major
      phospholipids, phosphatidylethanolamine and PmE, were measured in the frontal
      cortex, striatum, and cerebellum of the male progeny of the two groups at 60 d of
      age. The n-3 polyunsaturated fatty acid (PUFA) deficiency had no effect on the
      distribution of phospholipids in all brain regions but affected their acyl
      composition differently. The level of 22:6n-3 was significantly lower and
      compensated for by higher levels of n-6 fatty acids in all regions and
      phospholipids studied. However, docosahexaenoic acid, being more concentrated in
      the PmE of frontal cortex, is also more decreased in the n-3-deficient rats
      compared to the striatum. By contrast, striatum PmE has retained more 22:6n-3
      than PmE of the other regions. In addition, the increase of n-6 PUFA was
      significantly lower in frontal cortex PmE compared to the striatum and cerebellum
      PmE. In association with altered neurotransmission observed in frontal cortex of
      n-3-deficient rats, our results suggest that frontal cortex PmE might be more
      affected in chronically alpha-linolenic-deficient rats. However, by retaining
      22:6n-3, striatum PmE could be most resilient.

PMID- 9590629
TI  - Inhibitory effect of linoleic acid on chain elongation and desaturation of 18:2
      c,t isomers in lactating and neonatal rats.
AB  - The previous studies showed that dietary 18:2 c,t isomers could be chain
      elongated and desaturated to produce unusual 20:4 isomers. The present study was
      undertaken to determine the minimal amount of 18:2n-6 required to suppress the
      chain elongation and desaturation of 18:2 c,t isomers in the lactating and
      neonatal rats when animals were fed 15% partially hydrogenated canola oil diet
      containing 1.72% energy as 18:2 c,t isomers and varying amounts of free 18:2n-6.
      These diets induced marginal essential fatty acid (EFA) deficiency states (0.56%
      energy 18:2n-6) to EFA adequacy (2.56% energy 18:2n-6). After feeding for 50 d,
      the female animals were mated with males by overnight pairing. After conception,
      the lactating rats were killed, together with one pup from each dam, at term and
      day 26 of lactation. Two unusual 20:4 isomers in both maternal and neonatal liver
      phospholipids were identified as 20:4delta5c,8c,11c,14t and
      20:4delta5c,8c,11c,15t, which were derived from 18:2delta9c,12t and
      18:2delta9c,13t, respectively. The results showed that 18:2n-6 at about 2.0% of
      total energy in maternal diet was required to block the production of
      20:4delta5c,8c,11c,14t and 20:4delta5c,8c,11c,15t in the maternal liver, whereas
      18:2n-6 at about 2.5% of total energy in maternal diet was required to suppress
      production of these unusual 20:4 isomers in the neonatal liver.

PMID- 9590630
TI  - Conjugated linoleic acids alter bone fatty acid composition and reduce ex vivo
      prostaglandin E2 biosynthesis in rats fed n-6 or n-3 fatty acids.
AB  - This study evaluated the effects of conjugated linoleic acids (CLA) on tissue
      fatty acid composition and ex vivo prostaglandin E2 (PGE2) production in rats
      given diets varying in n-6 and n-3 fatty acids. Four groups of rats were given a
      basal semipurified diet (AIN-93G) containing 70 g/kg of added fat for 42 d. The
      fat treatments were formulated to contain CLA (0 vs. 10 g/kg of diet) and n-6
      (soybean oil having an n-6/n-3 ratio of 7.3) and n-3 fatty acids (menhaden oil +
      safflower oil having an n-6/n-3 ratio of 1.8) in different ratios in a 2 x 2
      factorial design. Fatty acids in liver, serum, muscle, heart, brain, spleen, and
      bone (cortical, marrow, and periosteum) were analyzed by capillary gas-liquid
      chromatography. The various dietary lipid treatments did not affect growth;
      however, CLA improved feed efficiency. The CLA isomers were found in all rat
      tissues analyzed although their concentrations varied. Dietary CLA decreased the
      concentrations of 16:1n-7, 18:1, total monounsaturates and n-6 fatty acids, but
      increased the concentrations of n-3 fatty acids (22:5n-3 and 22:6n-3), and
      saturates in the tissues analyzed. Ex vivo PGE2 production in bone organ culture
      was decreased by n-3 fatty acids and CLA. We speculate that CLA reduced the
      concentration of 18:1 fatty acids by inhibiting liver delta9-desaturase activity.
      The fact that CLA lowered ex vivo PGE2 production in bone organ culture suggests
      that these conjugated fatty acids have the potential to influence bone formation
      and resorption.

PMID- 9590631
TI  - Effects of dietary marine oils and olive oil on fatty acid composition, platelet
      membrane fluidity, platelet responses, and serum lipids in healthy humans.
AB  - The influence of various dietary marine oils and olive oil on fatty acid
      composition of serum and platelets and effects on platelets and serum lipids were
      investigated as part of an extensive study of the effects of these oils on
      parameters associated with cardiovascular/thrombotic diseases. Healthy volunteers
      (266) consumed 15 mL/d of cod liver oil (CLO); whale blubber oil (refined or
      unrefined); mixtures of seal blubber oil and CLO; or olive oil/CLO for 12 wk. In
      the CLO, seal oil/CLO, and whale oil groups, serum levels of eicosapentaenoic
      acid (EPA) were increased. In platelets, EPA was increased in the CLO, seal/CLO,
      and olive oil/CLO groups. The localization of n-3 polyunsaturated fatty acids in
      the triacylglycerols did not seem to influence their absorption. Intake of oleic
      acid is poorly reflected in serum and platelets. No significant differences in
      triacylglycerols (TG), total cholesterol, or high density lipoprotein cholesterol
      were observed, even though TG were reduced in the CLO, CLO/seal oil, and whale
      oil groups. Mean platelet volume increased significantly in both whale oil groups
      and the CLO/olive oil group. Platelet count was significantly reduced in the
      refined whale oil group only. Lipopolysaccharide-stimulated blood tended to
      generate less thromboxane B2 in CLO, CLO/seal, and CLO/olive groups. The whale
      oils tended to reduce in vivo release of beta-thromboglobulin. In conclusion,
      intake of various marine oils causes changes in platelet membranes that are
      favorably antithrombotic. The combination of CLO and olive oil may produce better
      effects than these oils given separately. The changes in platelet function are
      directly associated with alterations of fatty acid composition in platelet
      membranes.

PMID- 9590632
TI  - Contribution of meat fat to dietary arachidonic acid.
AB  - Arachidonic acid (AA) in the diet can be efficiently absorbed and incorporated
      into tissue membranes, resulting in an increased production of thromboxane A2 by
      platelets and increased ex vivo platelet aggregability. Results from previous
      studies have shown that AA is concentrated in the membrane phospholipids of lean
      meats. However, the concentration of AA in the visible fat portion of meats also
      may be significant despite being ignored in most studies. The aim of this study
      was to accurately quantitate the AA content of visible fat and the lean portion
      of beef, lamb, pork, chicken, duck, and turkey. The visible fat of meat contained
      a significant quantity of AA, ranging from 20 to 180 mg/100 g fat, whereas the AA
      content of the lean portion of meat was lower, ranging from 30 to 99 mg/100 g
      lean meat. Beef and lamb meats contained lower levels of AA in both the visible
      fat and lean portion than that from the other species. The highest level of AA in
      lean meat was in duck (99 mg/100 g), whereas pork fat had the highest
      concentration for the visible fats (180 mg/100 g). The lean portions of beef and
      lamb contained the higher levels of n-3 polyunsaturated fatty acids (PUFA)
      compared with white meats which were high in AA and low in n-3 PUFA. The present
      data indicate that the visible meat fat can make a contribution to dietary intake
      of AA, particularly for consumers with high intakes of fat from pork or poultry
      meat.

PMID- 9590633
TI  - Cycloserine-induced decrease of cerebroside in myelin.
AB  - L-Cycloserine has been shown specifically to lower brain cerebroside levels in
      vivo, but the extent to which the decrease in whole brain cerebroside content
      reflects lower myelin cerebroside levels is not known since a substantial portion
      of cerebroside is found in nonmyelin membranes. The present report demonstrates
      that chronically administered cycloserine lowers the proportion of cerebroside in
      rat brain myelin. Cycloserine-induced decrease of myelin cerebroside should
      provide a useful tool in investigating the role of cerebroside in maintaining
      myelin stability.

PMID- 9590634
TI  - Cemented total hip arthroplasty following previous femoral osteotomy: an average
      16-year follow-up study.
AB  - The indications for proximal femoral osteotomy would be substantially limited if
      it significantly compromised the outcome of a subsequent hip arthroplasty.
      Previous reports have followed only early cementing techniques over intermediate
      duration. This study comprised 22 primary cemented total hip arthroplasties
      performed by a single surgeon following failed proximal femoral osteotomies at an
      average follow-up period of 15.8 years. Three patients who died prior to the 11
      year minimum follow-up period are not included, leaving 19 hips for long-term
      review. All stems were cemented with second-generation techniques. Stem placement
      and collar-calcar contact, however, were substantially worse compared with
      historical control subjects. Eight reconstructions required custom miniature or
      calcar replacement components, and in 6 hips, the stems were inserted only in the
      diaphysis. Two of 19 femoral components (10.5%) were revised for aseptic
      loosening and 2 additional femoral components were loose. The average Harris hip
      score of those not revised was 80.4. Five acetabular components (26.3%) required
      revision. Four additional cups were loose, yielding a total acetabular loosening
      rate of 47.4% at 15.5 years. Intertrochanteric osteotomy in general did not
      affect the expected excellent results of the femoral component using modern
      cementing techniques. Severe deformity following subtrochanteric osteotomy,
      however, did adversely affect the outcome.

PMID- 9590635
TI  - Effect of locking mechanism on fluid and particle flow through modular acetabular
      components.
AB  - Six modular acetabular components were evaluated to determine whether screw holes
      in the metal shell offer a route for fluid and debris into the acetabular bone
      stock. A 56-mm acetabular shell for each trial was mounted to a sealed chamber
      and loaded at a 25 degrees angle under axial loads of 270-2,700 N and +/- 2.5-N-m
      torsional load. Polystyrene microspheres (average diameter, 0.5 microm) were
      placed in double-deionized water at 300 mmH2O pressure in a sealed chamber above
      the component. The only channel between the fluid above and the collecting
      chamber below was through the cup-liner interface and 1 screw hole. Fluid and
      debris in the collecting chamber were harvested after 1,000,000 cycles. The
      collected sample was filtered through a 0.2-microm-pore filter and analyzed under
      electron microscopy for evidence of microspheres. Water and polystyrene
      microspheres were isolated in the collecting chamber for all trials except the
      Reflection cup (Smith & Nephew Orthopaedics, Memphis, TN) with a screw hole cover
      and the Micro-Seal cup (Whiteside Biomechanics, St. Louis, MO) with a peripheral
      seal. A screw placed in the screw hole of the Reflection cup failed to seal the
      interface. The peripheral seal around the rim of the Micro-Seal polyethylene
      prevented fluid and particle flow between the metal shell and polyethylene liner.

PMID- 9590636
TI  - Total hip arthroplasty in juvenile chronic arthritis: a consecutive series.
AB  - Twenty-nine total hip arthroplasties in 16 patients with juvenile chronic
      arthritis were performed by one surgeon and followed prospectively. The 9 female
      and 7 male patients averaged 21 years of age (range, 14-35). Height and weight
      averaged 160 cm (63 inches) and 53 kg (118 lb.), respectively. Preoperative
      planning used small or miniature components to accommodate the small anatomic
      proportions of the hip. The femoral component was cementless in the majority
      (20/29), but required cementing in 10 of 29 hips because of poor bone stock. The
      acetabula were reconstructed with a porous-coated cup with or without screws
      (27/29) or with a cemented cup (2/29). Follow-up periods averaged 53 months
      (range, 24-100 months). The average Harris hip score improved from 37 to 78 after
      surgery (P = .0001). Pain relief was excellent; 15 of 16 patients (27/29 hips)
      expressed a significant improvement in daily function and lifestyle, despite
      systemic involvement of their arthritis. The range of motion of the hip improved
      significantly in all planes (P = .001). Two of the 4 uncemented Muller CDH
      components (Protek, Bern, Switzerland) with a large offset have migrated into
      varus; both are pain-free. One cemented femoral component has been revised
      because of aseptic loosening. The use of a small or miniature, cemented or
      cementless femoral component and a porous-coated cup appears to provide an
      excellent method of hip reconstruction for patients with juvenile chronic
      arthritis and small anatomic proportions; however, a femoral component with too
      great an offset should be avoided, because this may result in varus migration of
      the stem.

PMID- 9590637
TI  - Impact of a clinical pathway and implant standardization on total hip
      arthroplasty: a clinical and economic study of short-term patient outcome.
AB  - This study evaluates the impact of a clinical pathway (CP) and a hip implant
      standardization program (HISP) on the quality and cost of total hip arthroplasty
      (THA). Two hundred six unilateral THA operations for osteoarthritis were
      evaluated: 89 operations were performed in 1991 without a CP or HISP (4-year
      follow-up period); 117 operations were performed in 1993 with a CP and HISP (2
      year follow-up period). All patients had good clinical results and excellent
      outcomes with short-term follow-up evaluation. No differences were seen between
      groups in terms of patient ratings of outcome and satisfaction or in terms of
      complication rates in the hospital. Implementation of a CP and HISP did not
      adversely affect the short-term outcome of THA but did reduce hospital length of
      stay and hospital cost for THA.

PMID- 9590638
TI  - Cost-effectiveness of early surgical intervention in silent osteolysis.
AB  - Access to subspecialty care is the subject of significant controversy. Most
      managed-care systems closely monitor the number of specialist referrals as well
      as x-rays ordered for patients with no symptoms, but large lytic lesions can
      exist around implants without any pain. Intervention costs were calculated for 2
      groups of patients: 1 group with silent lysis with no symptoms and another group
      with periprosthetic fractures around lytic lesions. The costs were significantly
      higher in the group in which the fractures occurred versus the group in which
      early intervention was performed. Early diagnosis of structurally critical lytic
      lesions around implants by routine follow-up monitoring is recommended for all
      joint replacement patients.

PMID- 9590639
TI  - Effect of oxidation on delamination of ultrahigh-molecular-weight polyethylene
      tibial components.
AB  - Whether oxidation of ultrahigh-molecular-weight polyethylene (UHMWPE) causes
      delamination of the plastic in total knee arthroplasties (TKAs) was investigated.
      Examination of retrieved TKAs has shown that oxidation of UHMWPE can be caused by
      postirradiation damage leading to a subsurface band or, to a lesser extent, by
      mechanical forces during use leading to surface oxidation. Delamination cracks
      propagated through the subsurface oxidized band. In wear tests, delamination
      occurred in artificially aged UHMWPE where only subsurface oxidized bands had
      formed. Increased surface wear predominated where oxidation was associated with
      the surface of the plastic. Similarly, in tensile and fatigue tests of oxidized
      UHMWPE, there was a significant reduction in the ultimate tensile strength and in
      the fatigue resistance of specimens that had developed a subsurface band.
      Oxidation increased fatigue crack growth rate. It was observed that UHMWPE from
      different manufacturers varied in its resistance to oxidation. This study
      demonstrates that the effect of oxidation, which results in the development of a
      subsurface white band, combined with high subsurface shear forces observed in
      TKAs, is to enhance delamination wear.

PMID- 9590640
TI  - Wear in retrieved acetabular components: effect of femoral head radius and
      patient parameters.
AB  - Forty-seven explanted Porous Coated Anatomic (PCA, Howmedica, Rutherford, NJ)
      cementless acetabular components were acquired at revision surgery. All the
      components articulated against CoCrMo femoral heads of 32-mm diameter. The
      penetration depth and angle were measured using the shadowgraph technique. The
      wear volume was then calculated using Kabo's formula. Using weighted linear
      regression analysis, the mean penetration rate and mean volumetric wear rate were
      calculated to be 0.23 (SE, 0.03) mm3/y and 96 (SE, 13) mm3/y, respectively. The
      creep component was not found to be significantly different from zero. The
      clinical wear factor, k(clinical), for this cohort was also calculated using
      linear regression analysis but with the assumption that creep was zero. The value
      found, k(clinical) = 1.93 (SE, 0.29) x 10(-6) mm3/N-m, was similar to those in
      previous studies involving cemented joints with a 22-mm femoral head diameter.
      The similar k(clinical) values of these substantially different joint types
      suggest that the high volumetric wear rate for the PCA joint can be attributed
      entirely to its larger head size and the younger, more active, patient profile.
      Fixation technique and metal backing seem not to influence the rate of wear.

PMID- 9590641
TI  - An international comparative study of total hip arthroplasty cost and practice
      patterns.
AB  - The cost of total hip arthroplasty (THA) was assessed on a worldwide basis, with
      specific information obtained regarding implant type, cost, manufacturer,
      fixation method, as well as other clinical related practices. One hundred and ten
      orthopaedic surgeons representing 30 countries and 6 continents responded to the
      questionnaire. The average number of THAs per year per surgeon was 75 (range, 2
      300). Surgeons reported using all cemented components in 35% of THAs at an
      average cost of $1,536 (U.S. dollars). Uncemented components were used in 31% at
      an average cost of $2,674, and hybrid reconstructions in 34% at an average cost
      of $2,114. Almost half (44%) of the respondents stated that the hospital
      negotiated the type and price of the implants. Most surgeons (80%) indicated they
      were under pressure to decrease the cost of THA and 68% were under pressure to
      reduce the length of patients' hospital stay. When asked for recommended ways to
      reduce costs, 30% stated that negotiating a reduced implant price from the
      supplier was the most important measure. On a worldwide basis, there is
      tremendous variation in the cost and availability of implants. The reported cost
      for identical implants from a single manufacturer can vary as much as 700%. The
      comments of those responding are similar to the findings of surgeons here in the
      United States regarding cost containment and the role of reducing the length of
      hospital stay as well as negotiating reduced prosthesis and supply costs. The
      orthopaedic surgeon's practice pattern is a major determinant of total costs.

PMID- 9590642
TI  - Arthopor 2 acetabular component with screw fixation in primary hip arthroplasty:
      a 7- to 9-year follow-up study.
AB  - The first 100 consecutive primary hip arthroplasties with the Arthopor 2
      acetabular component (Joint Medical Products, Stamford, CT) with supplemental
      screw fixation performed by the senior author were prospectively studied. The
      mean patient age was 57 years. Seventy-seven cemented and 23 cementless stems
      were placed, with 32-mm femoral heads used in most of the patients. Eighty-six
      hips were reviewed at 7-8.8 years (mean, 7.8 years). The mean Harris hip score at
      final follow-up evaluation was 94 points. No cups have been revised, although 2
      cups in patients with radiation osteonecrosis were loose radiographically. One
      patient underwent revision of a severely worn liner. Despite a relatively high
      mean linear wear rate of 0.27 mm/y (range, 0.13-0.57 mm/y), no radiographic
      evidence of pelvic osteolysis was seen. The Arthopor 2 cup performed well with
      respect to pelvic osteolysis, despite the presence of substantial polyethylene
      debris. The relatively high polyethylene wear rate is attributed in part to the
      younger patient population and the use of 32-mm femoral heads paired with thin
      polyethylene liners.

PMID- 9590643
TI  - Rotator cuff repair during shoulder arthroplasty in rheumatoid arthritis.
AB  - A prospective study of 40 shoulder arthroplasties in patients with rheumatoid
      arthritis was performed to evaluate the results of rotator cuff repair at the
      time of arthroplasty. A large cuff tear was present in 21 shoulders, and good
      repair of the cuff was performed in 9. In the other shoulders the repair was
      considered insufficient. All patients were clinically evaluated using the
      Hospital for Special Surgery 100-point scoring system. The minimum follow-up
      period for inclusion in this study was 2 years. The quality of the repair of the
      ruptured cuff at the time of surgery had a significant influence on the
      postoperative clinical score (linear regression model, P = .002). The clinical
      score of the shoulders with good repair of the rotator cuff improved considerably
      and continued to improve even after the first-year follow-up examination.
      Meticulous repair of the ruptured cuff at the time of arthroplasty is
      recommended.

PMID- 9590644
TI  - Histologic and biochemical differences between osteolytic and nonosteolytic
      membranes around femoral components of an uncemented total hip arthroplasty.
AB  - The unique design characteristics of an uncemented femoral component were used to
      study differences in the periprosthetic membranes in the presence and absence of
      osteolysis. A component (Omniflex, Osteonics, Allendale, NJ) that has a large
      midportion of the stem that does not contact bone was studied. A membrane forms,
      even in the absence of bone resorption, in Gruen zones 3 and 5 of this component.
      Analysis of this membrane showed noninflammatory fibrous tissue, no or minimal
      particulate debris, and few macrophages. In contrast, analysis of membranes from
      osteolytic regions around the same prosthesis demonstrated typical inflammatory
      characteristics. Collagenase, gelatinase, and stromelysin expression was high in
      osteolytic membranes but was low in tissues from noninflammatory regions without
      osteolysis. The data suggest a sequence of events in periprosthetic membrane
      formation. A noninflammatory membrane initially forms between the bone and the
      prosthesis. This membrane is transformed into an inflammatory membrane by the
      influx of particulate debris. Matrix metalloproteinases are selectively expressed
      in regions of osteolysis, implicating these enzymes in periprosthetic bone loss
      and suggesting a possible level for pharmaceutical intervention to prevent or
      treat osteolysis. Formation of the noninflammatory membrane around the distal
      part of the prosthesis of this or similar designs in the absence of bone
      resorption implies that these tissue samples could serve as useful negative
      control tissues to identify factors present in osteolytic periprosthetic
      membranes.

PMID- 9590645
TI  - Long-term elution of antibiotics from bone-cement: an in vivo study using the
      prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) system.
AB  - A prospective study of 49 patients undergoing a modified 2-stage exchange
      arthroplasty for infected total hip and knee arthroplasties using the prosthesis
      of antibiotic-loaded acrylic cement (PROSTALAC) system with a variety of doses of
      tobramycin and vancomycin was performed. The intra-articular concentrations of
      tobramycin and vancomycin were measured at the time of removal of the PROSTALAC
      temporary spacer and reimplantation of a definitive joint arthroplasty
      prosthesis, at a mean 118 days following initial implantation. The 95% confidence
      interval of the intra-articular concentration of tobramycin (4.35-123.88 mg/L)
      was entirely above the breakpoint sensitivity limit for sensitive organisms when
      at least 3.6 g of tobramycin was used per package of bone-cement but was entirely
      below it when at most 2.4 g was used. Vancomycin elution was not as good;
      however, detectable levels were still present in most patients. There was a
      statistically significant increase in the elution of vancomycin when the dose of
      tobramycin was increased from at most 2.4 g to at least 3.6 g. The dose of
      vancomycin in the cement did not influence the elution of either tobramycin or
      vancomycin. On the basis of these results, the use of at least 3.6 g of
      tobramycin and 1 g of vancomycin per package of bone-cement is recommended when
      antibiotic-loaded cement spacers are used in 2-stage exchange arthroplasty for
      infected total hip and knee arthroplasties.

PMID- 9590646
TI  - Metal-on-metal articulation in total hip arthroplasty: the case for improving
      metal- or ceramic-on-polyethylene.

PMID- 9590647
TI  - Metal-on-metal articulation in total hip arthroplasty: the case for using metal
      on-metal.

PMID- 9590648
TI  - Technique for acetabular liner revision in a nonmodular metal-backed component.
AB  - Use of a new technique for revising the acetabular liner when approaching a
      revision of a nonmodular metal-backed component is described. An overview of the
      method, its rationale, and 2 case reports are presented.

PMID- 9590649
TI  - Particulate debris presenting as radiographic dense masses following total knee
      arthroplasty.
AB  - Two cases of failed total knee arthroplasty associated with significant titanium
      debris that created massive radiographic densities are reported. The similarities
      of the failed total knee arthroplasties are that both involve titanium femoral
      components with failed metal-backed patellar components. At the time of surgical
      intervention, patellar polyethylene dissociation from metal-backed patellar
      components was noted with excessive burnishing and wear of the remaining metal
      backed patellar component and of the titanium femoral component. Wear of the
      tibial polyethylene was noted in both cases. The titanium-on-titanium wear couple
      produced significant debris, resulting in large mass formation about the total
      knee arthroplasty. Additionally, there were loculated, fluid-filled sacks of
      titanium debris. Histologic sections performed for both cases revealed
      significant deposits of titanium in combination with polyethylene. In both cases,
      radiographs revealed the presence of large, radiodense masses. These cases
      illustrate that when considering etiologies for radiodense masses about total
      joint arthroplasty, particulate titanium debris resulting in mass formation must
      be added to the differential diagnosis.

PMID- 9590650
TI  - Total hip arthroplasty in an adult with proximal femoral focal deficiency.
AB  - A 40-year-old woman with isolated unilateral proximal femoral focal deficiency
      presented with 2 years of gradually increasing left hip pain that interfered with
      her activities of daily living. A total hip arthroplasty was performed through a
      posterior approach. At 12 months, she had minimal discomfort about the hip, a
      markedly increased level of activity, and improved gait, and she required no
      ambulatory aids. This procedure is cautiously recommended for use in selected
      patients with proximal femoral focal deficiency.

PMID- 9590651
TI  - Interprosthetic fracture of the femoral shaft.
AB  - Experience in the management of a complication of ipsilateral hip and knee
      arthroplasty is described. The cases of four female patients who sustained a
      femoral shaft fracture after ipsilateral hip and knee arthroplasty are reported.
      All fractures were treated operatively, and in all cases internal fixation
      devices failed. This complication of multiple joint arthroplasty presents a
      difficult management problem. Rigid fixation has a high failure rate for this
      type of fracture. Surface knee arthroplasty provides a better opportunity for
      internal fixation than a knee arthroplasty with a stemmed femoral component.

PMID- 9590652
TI  - The membrane-bound isoform of stem cell factor synergizes with soluble flt3
      ligand in supporting early hematopoietic cells in long-term cultures of normal
      and aplastic anemia bone marrow.
AB  - The hematopoietic growth factors stem cell factor (SCF) and flt3 ligand (flt3L)
      are produced within the hematopoietic microenvironment in a membrane-bound and
      soluble isoform. To elucidate the relevance of the two isoforms in the network of
      early-acting cytokines, we examined the interaction of membrane-bound SCF with
      the soluble forms of SCF and flt3L in long-term cultures of human bone marrow
      cells. Feeder layers of the murine SCF-deficient Steel stromal cell line
      transfected with human cDNA stably expressing SCF as a transmembrane molecule
      were used to support growth of mononuclear cells and CD34+ progenitors derived
      from normal human bone marrow or from hypoplastic marrow of patients with
      aplastic anemia (AA). The output of nonadherent progenitor cells representing
      colony-forming units (CFU) and high-proliferative potential colony-forming cells
      (HPP-CFC) was scored weekly in secondary methylcellulose cultures; the number of
      colonies derived from long-term culture-initiating cells (LTC-IC) was determined
      in nonadherent and adherent cells at 5 weeks. Membrane-bound SCF expressed in the
      stromal layer was more effective than soluble SCF and soluble flt3L in
      maintaining clonogenic progenitors. Furthermore, the transmembrane form of SCF
      effectively synergized with both exogenously supplied factors, although the
      effect of flt3L was superior to the effect of soluble SCF. In cultures of normal
      bone marrow cells, addition of flt3L enhanced the total number of CFU and HPP-CFC
      type progenitors, primarily of the granulocyte/macrophage lineage, by six- to
      ninefold after 3 weeks and of LTC-IC-derived colonies by 13-fold after 5 weeks of
      culture. In cultures of AA cells, both the number and the survival rate of
      clonogenic precursors were severely impaired even in the presence of flt3L,
      which, however, yielded a two- to sixfold enhancement of CFU and HPP-CFC numbers
      at 1 to 2 weeks. In comparison with the hematopoietic function of human Dexter
      type stroma cultures, murine feeders expressing high levels of membrane
      associated human SCF were equivalent in supporting hematopoiesis during the
      initial 3 to 4 culture weeks when supplemented with flt3L. These results
      demonstrate that soluble flt3L interacts with membrane-bound SCF in supporting
      the long-term growth of bone marrow progenitor cells. The hypothesis that SCF and
      flt3L function synergistically during the very early stages of human
      hematopoiesis is thereby reinforced.

PMID- 9590653
TI  - A neutralizing anti-TGF-beta1 antibody promotes proliferation of CD34+Thy-1+
      peripheral blood progenitors and increases the number of transduced progenitors.
AB  - The subset of blood cells that expresses both CD34 and Thy1 (CD90) cell surface
      molecules is enriched in hematopoietic stem cell activity and can be obtained
      from the peripheral blood of cancer patients after mobilization by chemotherapy
      and granulocyte colony-stimulating factor (G-CSF). Because transforming growth
      factor-beta1 (TGF-beta1) is a potent inhibitor of hematopoietic progenitor
      proliferation and differentiation, in this study we analyzed the impact of
      neutralizing TGF-beta1 activity during culture and retroviral transduction of
      CD34+Thy1+ cells. When purified CD34+Thy1+ cells were cultured in the presence of
      a neutralizing antibody against TGF-beta1, the percentage of cycling cells,
      proliferation, and absolute number of clonogenic progenitors were increased in
      comparison to the cultures performed without the addition of antibody. Antibody
      mediated neutralization of TGF-beta1 during retroviral transduction performed by
      coculture of CD34+Thy1+ cells with a MFG-S-nlsLacZ retroviral vector-producing
      cell line did not affect the percentage of transduced progenitors as assessed by
      direct X-Gal staining of colonies in clonogenic assays. However, due to the
      better expansion of CD34+Thy1+ cells in the presence of anti-TGF-beta1, the
      absolute number of transduced progenitors recovered at the end of the culture was
      increased.

PMID- 9590654
TI  - Hematopoiesis-promoting activity of rat liver biliary epithelial cells:
      involvement of a cell surface molecule, liver-regulating protein.
AB  - Stromal cell lines from bone marrow and other blood-forming organs including
      fetal liver have been found to support hematopoiesis. In this paper, we
      demonstrate that rat liver biliary epithelial cells (RLEC), most likely
      originating from primitive bile ductules, are able to support long-term
      hematopoietic cell growth as well as burst-forming unit-erythroid (BFU-E) and
      colony-forming unit-granulocyte/macrophage (CFU-GM) production. RLEC have
      previously been shown to express a cell surface molecule named liver-regulating
      protein (LRP), which is involved in the long-term maintenance of hepatocyte
      functions in a coculture system. In addition, LRP-like molecules have been found
      in spleen, thymus, lymph nodes, and peripheral blood cells. In the present study,
      we found that hematopoietic cells and several stromal cell types from bone marrow
      were LRP-positive, and immunoprecipitation revealed polypeptides similar to those
      found in RLEC. We then investigated the biological role of LRP on hematopoiesis
      using short-term RLEC and bone marrow stromal cell culture systems. Addition of
      specific anti-LRP antibody to both systems reduced hematopoietic cell
      proliferation and committed progenitor production, whereas it did not directly
      affect the clonal proliferation and maturation of these progenitors in
      methylcellulose assays. Moreover, using diffusible chamber cultures that suppress
      direct contacts with hematopoietic cells, we observed low cell growth and no
      effect of monoclonal antibody (mAb) L8 treatment. All these results strongly
      argue for a cell proximity signal mediated by RLEC and bone marrow stromal cells
      and for the involvement of LRP-like molecules in this signal in liver and bone
      marrow hematopoietic function.

PMID- 9590655
TI  - Depletion of EBV-infected cells in donor marrow by counterflow elutriation.
AB  - Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative
      disease (PTLD) is a well-recognized complication of T cell-depleted (TCD)
      allogeneic bone marrow transplantation (BMT). Certain methods of TCD, such as
      counterflow elutriation (CE), have not been associated with an increased
      incidence of PTLD. Since CE depletes B cells as well as T cells, the hypothesis
      that CE depletes donor marrow of EBV-infected cells was tested in this study.
      Marrow samples from 70 donors were assayed by qualitative and semi-quantitative
      polymerase chain reaction (PCR) amplification to detect EBV DNA in four cellular
      fractions produced by elutriation: a small cell fraction (F70), two intermediate
      sized cell fractions (F110 and F140), and a large cell (hematopoietic precursor
      enriched, lymphocyte-depleted) rotor-off (R/O) fraction. The distribution of B
      cells in elutriation fractions was 21% (F70), 59% (F110), 18% (F140), and 2%
      (R/O). Qualitatively, the frequency of EBV DNA detected in fractions was 49%
      (F70), 57% (F110), 73% (F140), and 44% (R/O). The relative concentration of EBV
      DNA in each fraction was determined by semiquantitative PCR. The mean number of
      EBV DNA copies per 150,000 cells was 0.57 (F70), 4.6 (F110), 5.7 (F140), and 0.61
      (R/O). Relative EBV DNA load in each fraction was calculated by multiplying the
      mean concentration of EBV DNA per fraction and mean mononuclear cell content in
      each fraction. The relative distribution of EBV DNA was 0.5, 58, 40, and 1.5% in
      the F70, F110, F140, and R/O fractions, respectively. No correlation between the
      amount of EBV in the graft and development of PTLD could be made, because only
      one of the 70 recipients developed PTLD and this was following autologous
      hematopoietic recovery. Although these results demonstrate that the majority of
      EBV-infected cells in marrow are separated from the TCD graft by counterflow
      elutriation, further studies are required to differentiate the role of this
      phenomenon from that of other potential factors, such as the amount of T cell
      depletion and recovery of EBV immunity in the pathogenesis of PTLD after BMT.

PMID- 9590656
TI  - A nylon wool filter coated with human immunoglobulin for rapid depletion of
      monocytes and myeloid cells from peripheral blood stem cell transplants.
AB  - The aim of this study was to develop an inexpensive method for reducing the
      number of differentiated cells from granulocyte colony-stimulating factor
      mobilized leukocytapheresis products (LPs) containing peripheral blood stem
      cells. Analysis of LPs showed the presence of significant numbers of monocytes
      and myeloid cells. The myeloid cells represented largely immature stages of the
      granulocyte lineage (myelocytes and metamyelocytes). We investigated whether
      these cells could be selectively depleted by filtration over nylon wool.
      Filtration of LP samples over nylon wool in a medium containing fetal calf serum
      resulted in variable but on average low yields of CD34+ cells (48 +/- 30%; n=13)
      and strongly variable depletions of myeloid cells. The adherence of CD34+ cells
      to the polyamide fiber was partially mediated by activated platelets that were
      present in the LPs. Removal of platelets by counterflow centrifugal elutriation
      before filtration resulted in increased yields of CD34+ cells in the filtrates
      (65 +/- 13%; n=10). The yield of progenitor cells was similarly enhanced when
      trisodium citrate, a chelating substance, was added to the filtration medium.
      Adherence of the myeloid cells to the nylon fiber was promoted by preincubation
      of the columns with human immunoglobulin (Ig) (2 mg/mL). Small-scale filtrations
      of LP samples in the presence of trisodium citrate over columns with Ig-coated
      nylon wool resulted in removal of 96 +/- 4% of the monocytes and 74 +/- 18% of
      the myeloid cells, with a yield of 71 +/- 15% CD34+ cells and 67 +/- 10%
      granulocyte-monocyte colony-forming units (CFU-GM) (n=23). There was no loss of
      primitive stem cells during the procedure: the yield of late-appearing
      cobblestone area-forming cells (CAFCs, week 6) was 110 +/- 30% (n=4). CFU-GM
      production per CAFC-derived clone was unchanged upon filtration, indicating that
      the quality of stem cells was not affected. Moreover, the proportions of CD34+
      cells expressing a primitive immunophenotype (CD38low or Thy-1+) were unchanged
      after filtration. Further enrichment of progenitor cells was obtained by
      separation of LP samples by elutriation before filtration. The combination of
      these two techniques resulted in complete removal of platelets, 89 +/- 7%
      depletion of erythrocytes, and 91 +/- 6% reduction of leukocytes, with a 50%
      yield of CD34+ cells (n=14). In conclusion, we have developed a rapid filtration
      technique by which monocytes and myeloid cells can be depleted from LP samples,
      with only minor loss of colony-forming cells and complete recovery of primitive
      stem cells.

PMID- 9590658
TI  - High frequency of donor chimerism after allogeneic transplantation of CD34+
      selected peripheral blood cells.
AB  - Ex vivo T cell depletion of allogeneic grafts is associated with a high (up to
      80%) rate of mixed chimerism (MC) posttransplantation. The number of transplanted
      progenitor cells is an important factor in achieving complete donor chimerism in
      the T cell depletion setting. Use of granulocyte colony-stimulating factor (G
      CSF) peripheral blood allografts allows the administration of large numbers of
      CD34+ cells. We studied the chimeric status of 13 patients who received
      allogeneic CD34+-selected peripheral blood progenitor cell transplants (allo
      PBPCTs/CD34+) from HLA-identical sibling donors. Patients were conditioned with
      cyclophosphamide (120 mg/kg) and total-body irradiation (13 Gy in four
      fractions). Apheresis products were T cell-depleted by the immunoadsorption
      avidin-biotin method. The median number of CD34+ and CD3+ cells infused was
      2.8x10(6)/kg (range 1.9-8.6x10(6)/kg) and 0.4x10(6)/kg (range 0.3-1x10(6)/kg),
      respectively. Molecular analysis of the engraftment was performed using
      polymerase chain reaction (PCR) amplification of highly polymorphic short tandem
      repeat (PCR-STR) sequences in peripheral blood samples. MC was detected in two
      (15%) of 13 patients. These two patients relapsed at 8 and 10 months after
      transplant, respectively. The remaining 11 patients showed complete donor
      chimerism and were in clinical remission after a maximum follow-up period of 24
      months (range 6-24 months). These results were compared with those obtained in 10
      patients who were treated with T cell-depleted bone marrow transplantation by
      means of elutriation and who received the same conditioning treatment and similar
      amounts of CD3+ cells (median 0.45x10(6)/kg; not significant) but a lower number
      of CD34+ cells (median 0.8x10(6)/kg; p = 0.001). MC was documented in six of 10
      patients (60%), which was significantly higher than in the allo-PBPCT/CD34+ group
      (p = 0.04). We conclude that a high frequency of complete donor chimerism is
      achieved in patients receiving allo-PBPCT/CD34+ and that this is most likely due
      to the high number of progenitor cells administered.

PMID- 9590657
TI  - Allogeneic bone marrow or peripheral blood cell transplants in adults with
      hematologic malignancies: a single-center experience.
AB  - This is a retrospective study of 97 patients who received either allogeneic bone
      marrow transplant (BMT) (n=52) or peripheral blood cell transplant (PBCT) (n=45)
      at our institution from human leukocyte antigen (HLA)-identical sibling donors
      between January 1994 and January 1997. The two groups were comparable with
      respect to diagnosis, age, sex, interval from diagnosis, and disease phase. They
      were prepared with cyclophosphamide (CY) and fractionated total-body irradiation
      (TBI) (n=51) or CY and thiotepa (n=46). Graft-vs.-host disease (GVHD) prophylaxis
      consisted of cyclosporin A and methotrexate. Patients who received PBCT exhibited
      faster neutrophil engraftment (day 14 vs. day 16, p = 0.002) than those in the
      BMT group, as well as higher platelet counts on day 20 (32x10(9)/kg vs.
      21x10(9)/kg, p = 0.001), but graft function as assessed by platelet counts on
      days 50, 100, and thereafter was comparable. The number of days spent in the
      hospital, days on intravenous antibiotics, and days of fever were lower in the
      PBCT group, but not significantly. Acute GVHD, chronic GVHD, and cytomegalovirus
      infections were comparable between the two groups. The overall actuarial 3-year
      transplant-related mortality (TRM) rate for BMT vs. PBCT patients was 20 vs. 33%
      (p = 0.1), the survival rate was 53 vs. 48% (p = 0.3), and the relapse rate was
      42 vs. 43% (p = 0.8). For patients in first complete remission, these figures
      were TRM 12 vs. 22% (p = 0.2), survival rate 75 vs. 70% (p = 0.4) and relapse
      rate 31 vs. 9% (p = 0.4), respectively, for the BMT and PBCT groups. These data
      suggest that the short-term outcome of allogeneic PBCT is not significantly
      different from that of allogeneic BMT in patients with hematologic malignancies.
      Long-term results are not available at present.

PMID- 9590659
TI  - Recombinant gene products of two natural variants of the human cytidine deaminase
      gene confer different deamination rates of cytarabine in vitro.
AB  - The recent cloning of human cytidine deaminase (CDD) revealed two variants with a
      nonconservative amino acid deviation (Gln<-->Lys) at codon 27 within a region of
      structural homology to a core domain of bacterial CDDs. We here confirm the
      occurrence of both CDD sequences by cDNA cloning and show that at cytarabine (ara
      C) concentrations of 1x10(-8) to 2x10(-2) M, the recombinant enzyme corresponding
      to the Lys-carrying natural variant (CDD-2) exerts a 1.3- to 3.3-fold higher in
      vitro deamination rate of ara-C than the Gln-carrying enzyme (CDD-1). These
      results suggest that this genetic polymorphism contributes to the different
      deamination phenotypes of ara-C observed in vivo, and that investigation of CDD
      allelotype frequencies and their correlation with ara-C resistance in patients
      with acute leukemia may be warranted. In addition, our data may be relevant to
      recently considered CDD gene transfer strategies for the detoxification of
      hematopoietic stem cells during high-dose therapy with cytosine nucleoside
      analogs.

PMID- 9590660
TI  - Quantitative assessment of hematopoietic chimerism after allogeneic bone marrow
      transplantation has predictive value for the occurrence of irreversible graft
      failure and graft-vs.-host disease.
AB  - Primary graft failure, secondary to either host-vs.-graft reaction or delayed
      engraftment, and graft-vs.-host disease (GVHD) are among the most difficult
      clinical problems to manage in the field of allogeneic bone marrow
      transplantation (BMT). Early diagnosis of both conditions would greatly improve
      their outcome. Using fluorescence in situ hybridization (FISH) with an X- and Y
      probe mixture, we sequentially monitored chimerism of neutrophils and lymphoid
      cells from day 1 to 100 in 28 consecutive recipients of sex-mismatched
      unmanipulated bone marrow grafts. The objective was to quantitatively assess the
      evolution of chimerism during this crucial time interval and to determine whether
      chimerism patterns would be predictive of engraftment and GVHD. In recipients
      with primary graft failure (n=7), the presence of donor-type neutrophils and NK
      cells as well as the predominance of donor-type T cells distinguished patients
      who responded to G-CSF (n=5) from nonresponders (n=2). Furthermore, the clearance
      of host CD3+CD56- cells during days 5-10 posttransplantation was significantly
      hastened in patients who subsequently developed acute (delta=80%) or chronic
      (delta=81%) GVHD compared with patients without GVHD (delta=17%). Thus, our data
      suggest that molecular monitoring of the fate of host/donor hematopoietic cells
      in the early posttransplantation period could be useful in differentiating
      patients with delayed engraftment from those with irreversible rejection and in
      predicting the occurrence of GVHD as soon as day 10. This investigational
      approach may provide an appropriate basis on which to select adequate treatment
      for primary graft failure and high-risk candidates that could benefit from novel
      preemptive therapies for GVHD.

PMID- 9590661
TI  - Spontaneous intramedullary apoptosis is present in disorders other than
      myelodysplasia.
AB  - Myelodysplastic syndrome (MDS) is a group of hematopoietic disorders
      characterized by peripheral cytopenias in the presence of normo- or hypercellular
      dysplastic marrow. It has been suggested that premature intramedullary apoptosis
      may contribute to this phenomenon. We used terminal dUTP nick-end labeling
      (TUNEL) of bone marrow biopsy specimens and cytocentrifuge preparations from
      patients with MDS and a variety of other hematopoietic disorders to determine
      whether there is increased intramedullary apoptosis in MDS and whether any such
      effect is specific to MDS. TUNEL labeling of bone marrow from 24 patients with
      MDS revealed significant positivity in 10 of 11 patients with refractory anemia
      (RA), five of seven with RA and excess of blasts (RAEB), all three patients with
      RAEB in transformation (RAEB-t), and all three patients with RA with ring
      sideroblasts (RARS). The percent of positive cells ranged from 5 to 50% but
      showed no apparent correlation with morphological subtype. In a series of 29
      patients with acute leukemia, 17 showed significant positivity (13 of 13 with
      myeloid disease: three M1, seven M2, one M3, two M4; four of 16 patients with
      lymphoid disease: one Burkitt-type lymphoma, two null acute leukemia, and one
      common acute lymphoid leukemia). Intramedullary apoptosis was associated with
      myeloid or early committed progenitor cells and was highest in secondary acute
      myeloid leukemia (AML). Normal bone marrow samples from 12 individuals showed no
      evidence of apoptosis. Our results suggest that an increased level of
      intramedullary apoptosis is apparent in both patients with MDS and those with
      AML; those with secondary AML have the highest levels. The relative absence of
      such findings in lymphoid malignancy suggests that the apoptotic pathways are
      different in this lineage.

PMID- 9590662
TI  - Equal distribution of competitive long-term repopulating stem cells in the CD34+
      and CD34- fractions of Thy-1lowLin-/lowSca-1+ bone marrow cells.
AB  - CD34 antigen is present on most, if not all, human hematopoietic stem cells
      (HSCs). Consistent with this pattern of expression, we recently reported that
      primitive murine HSCs defined as competitive long-term repopulating units (CRUs)
      are highly enriched among CD34+ bone marrow (BM) cells (one CRU/2500 cells).
      However, in agreement with one recent report that some murine HSCs do not express
      CD34 (Science 273:242), we observed that 15% of phenotypically defined Thy
      1lowLin-/lowSca-1+ (TLS) stem cells were CD34- by fluorescence-activated cell
      sorting. To examine further the nature of CD34 expression on murine hematopoietic
      cells, we separated TLS cells into CD34+ (0.022% of BM cells) and CD34- (0.005%
      of BM cells) fractions, confirmed their phenotype by reverse transcriptase
      polymerase chain reaction analysis of CD34 transcripts, and evaluated them in a
      variety of in vitro and in vivo assays. The CD34+ TLS population contained most
      (93-95%) of the day 12 spleen colony-forming units (CFU-S) and in vitro colony
      forming cells (CFCs). Cobblestone area-forming cells (CAFCs) able to proliferate
      on a murine bone marrow stromal cell line (SyS-1) represented one of every 5
      CD34+ TLS and one of every 31 CD34 TLS cells. When lethally irradiated mice were
      injected with 100 CD34+ TLS cells, all animals survived and began to recover
      circulating leukocytes, platelets, and erythrocytes by 15 days. In contrast, only
      40% of mice injected with 100 CD34- TLS cells were radioprotected, and
      hematopoietic reconstitution in surviving mice was not apparent until 21 days.
      The frequency of CRUs in CD34+ and CD34 TLS cells was determined by injecting
      limiting numbers of cells into lethally irradiated Ly-5 congenic hosts together
      with 10(5) "compromised" BM cells to provide radioprotection. CRUs able to
      regenerate and maintain lymphoid and myeloid cells for at least 6 months in
      primary and 5 months in secondary hosts represented one of every 156 CD34+ TLS
      and one of every 35 CD34- TLS cells. However, when normalized for the proportion
      of TLS cells that were CD34+ or CD34-, it was determined that the recovery of CRU
      among CD34+ and CD34- TLS cells was equivalent (46% and 54%, respectively). These
      data are consistent with the previous description of repopulating HSCs among CD34
      c-kit+Sca-1+Lin- cells (Science 273:242, 1996) and provide additional evidence
      that TLS cells are functionally heterogeneous and can be further fractionated on
      the basis of CD34 expression. Overall, approximately 95% of CFCs, CFU-S, and
      CAFCs in the TLS population were found to be CD34+, whereas more primitive CRU
      were distributed equally among CD34+ and CD34 TLS cells. These results should
      enable better characterization of the most primitive stem cells in murine BM.

PMID- 9590663
TI  - Brain tonics for brain sprouts: how neurotrophic factors fertilize neurons.

PMID- 9590664
TI  - Rapid titration of mood stabilizers predicts remission from mixed or pure mania
      in bipolar patients.
AB  - BACKGROUND: Recent investigations have suggested that the antimanic agents
      divalproex sodium and carbamazepine may each hasten hospital discharge and be
      especially beneficial in treating mixed-state mania. This study retrospectively
      compared the time to remission for pure versus mixed manic bipolar inpatients who
      were taking lithium, divalproex, or carbamazepine, or their combination, under
      naturalistic conditions. METHOD: Records were reviewed for 120 bipolar inpatients
      from 1991 to 1995. Research DSM-III-R diagnoses of pure or mixed mania were
      assigned along standardized guidelines. Data were obtained on daily symptoms,
      medication doses, and blood levels. Weekly improvement was evaluated by Kaplan
      Meier survival analysis of Clinical Global Impressions scale scores. Variables
      associated with "remission" versus "nonremission" were examined by logistic
      regression. RESULTS: Mixed mania (N = 70) was more common than pure mania (N =
      50). No significant differences were observed in the time to remission for mixed
      or pure manic bipolar patients who took lithium compared with those who took
      divalproex or carbamazepine. In patients who remained symptomatic with lithium as
      a single-agent mood stabilizer despite therapeutic serum lithium levels, the
      addition of a second mood stabilizer led to rapid symptom improvement. Among all
      medication subgroups, the speed with which patients achieved therapeutic blood
      levels of any of these agents significantly affected the time to remission.
      CONCLUSION: Mixed manic bipolar patients taking lithium, divalproex, or
      carbamazepine under naturalistic conditions remit at comparable rates. Those
      failing to respond to single-agent mood stabilizers often receive combinations of
      mood stabilizers. However, delays in optimizing a medication regimen may
      attenuate short-term outcome, regardless of the mood stabilizer selected. Rapid
      achievement of therapeutic blood levels of any antimanic agent appears to be
      strongly related to swift symptom remission.

PMID- 9590665
TI  - Opioid antagonists in the treatment of impulse-control disorders.
AB  - BACKGROUND: Symptoms of impulse-control disorders are generally refractory to
      psychotherapeutic or pharmacologic treatments. Recent study results suggest that
      opioid antagonists may reduce human urges, one of the core symptoms of impulse
      control disorders. The author discusses the rationale for and the potential
      utility of the opioid antagonists in the treatment of impulse-control disorders.
      METHOD: Work by preclinical and clinical investigators on the subject of
      motivation and its contextually relevant behavior is reviewed. The review
      includes the pharmacologic modulation of the motivation or drive and subsequent
      changes in behavior in animals and humans. On the basis of these reviews, the
      author prescribed naltrexone for up to 9 months to 15 patients who had impulse
      control disorder, and 3 select cases are reported. RESULTS: Naltrexone was
      generally well tolerated, and there were no hepatic side effects. Naltrexone
      appears to reduce urge-related symptoms and decreases the problematic behaviors
      such as pathological gambling. The effect appears to be sustained. In general, 50
      mg/day of naltrexone was not effective. Most patients required higher doses.
      Results were similar in the 12 other cases not reported here. CONCLUSION:
      Naltrexone may be of use in select impulse-control disorder patients. Other
      opioid antagonists such as nalmefene also need to be tested. Until controlled
      study data become available, the present report should be viewed as preliminary.

PMID- 9590666
TI  - Efficacy and safety of fluvoxamine in body dysmorphic disorder.
AB  - BACKGROUND: Body dysmorphic disorder (BDD), a preoccupation with an imagined or
      slight defect in appearance, has been noted in case reports, retrospective
      studies, and clinical series to respond to serotonin reuptake inhibitors (SRIs).
      These data further suggest that the delusional variant of BDD (delusional
      disorder, somatic type) may also respond to SRIs. However, systematic
      pharmacologic treatment studies of BDD and its delusional variant are needed.
      METHOD: Thirty subjects with BDD or its delusional variant (DSM-IV) were
      prospectively treated in an open-label fashion with fluvoxamine for 16 weeks.
      Subjects were assessed at regular intervals with the Yale-Brown Obsessive
      Compulsive Scale Modified for BDD (BDD-YBOCS), the Clinical Global Impressions
      (CGI) scale, the Hamilton Rating Scale for Depression, the Brown Assessment of
      Beliefs Scale, and other measures. RESULTS: BDD-YBOCS scores (mean +/- SD)
      decreased from 31.1 +/- 5.4 at baseline to 16.9 +/- 11.8 at termination (p <
      .001). Nineteen (63.3%) subjects were rated as responders on the BDD-YBOCS and
      the CGI (10 [33.3%] were much improved, and 9 [30.0%] were very much improved).
      Delusional subjects were as likely to respond to fluvoxamine as nondelusional
      subjects, and delusionality significantly improved. All 5 responders who were
      delusional at baseline were no longer delusional at study endpoint. The mean dose
      of fluvoxamine was 238.3 +/- 85.8 mg/day, and mean time to response was 6.1 +/-
      3.7 weeks. Fluvoxamine was generally well tolerated. CONCLUSION: These results
      suggest that fluvoxamine is a safe and effective treatment for BDD, including its
      delusional disorder variant. Controlled treatment trials are needed to confirm
      these findings.

PMID- 9590667
TI  - Medication compliance among patients with bipolar disorder and substance use
      disorder.
AB  - BACKGROUND: This study examined patterns of medication compliance and reasons for
      noncompliance among patients with bipolar disorder and substance use disorder.
      METHOD: Forty-four patients with current bipolar disorder and substance use
      disorder were administered a structured interview regarding lifetime compliance
      with prescribed psychotropic medications. RESULTS: Patients who were prescribed
      both lithium and valproate were significantly (p = .03) more likely to report
      full compliance with valproate than with lithium. Side effects were the most
      common reason for lithium noncompliance, but were not cited as a reason for
      valproate noncompliance. Also, a common pattern of noncompliance among patients
      prescribed benzodiazepines, neuroleptics, and tricyclic antidepressants was the
      use of more medication than prescribed. CONCLUSION: Valproate may have greater
      acceptability than lithium among patients with bipolar disorder and substance use
      disorder. Clinicians should also be aware that these patients may take higher
      doses of medication than prescribed.

PMID- 9590668
TI  - Buspirone and imipramine for the treatment of major depression in the elderly.
AB  - BACKGROUND: The current study was designed to assess the safety and efficacy of
      imipramine and buspirone in the treatment of major depression in elderly
      depressed attendees of primary care practices. METHOD: 177 patients aged 65 and
      over (mean age = 72 years; range, 65-89) who met DSM-III-R criteria of unipolar
      major depression with a minimum Hamilton Rating Scale for Depression score of 18
      were randomly assigned to 8 weeks of double-blind, placebo-controlled treatment
      with flexible doses of either imipramine or buspirone. RESULTS: Moderate to
      marked global improvement after 8 weeks of treatment (LOCF analysis) occurred in
      70% of patients treated with imipramine, 61% of patients treated with buspirone,
      and 42% of patients treated with placebo (chi2 = 9.1, df = 2, p < .02). Drug
      treatment was well tolerated, with 77% of imipramine- and 61% of buspirone
      treated patients completing 8 weeks of therapy. Imipramine/placebo differences
      were present from week 2 on, but buspirone/placebo differences occurred only at
      week 8. The presence of comorbid medical illness or concomitant use of
      nonpsychiatric prescription medications was not associated with poorer
      antidepressant response, increased adverse effects, or study attrition.
      CONCLUSION: Imipramine and to a lesser extent buspirone were found to be
      effective and well tolerated in the treatment of elderly depressed outpatients.

PMID- 9590669
TI  - Relation of serum anticholinergicity to cognitive status in schizophrenia
      patients taking clozapine or risperidone.
AB  - BACKGROUND: A potential beneficial outcome of treatment with certain of the
      atypical neuroleptics is the reduced risk of cognitive impairment, stemming from
      purported low affinity for cholinergic receptors. In vitro experiments have shown
      that clozapine is highly anticholinergic and risperidone is minimally so. In vivo
      tests of the anticholinergic burden imposed by these medications and its
      potential cognitive consequences are needed. This study examines anticholinergic
      burden in schizophrenia patients taking clozapine and risperidone and tests
      whether this burden is associated with cognitive deficits. METHOD: Serum
      anticholinergic levels were determined in a sample of 22 chronic schizophrenia
      patients using the radioreceptor assay method of Tune and Coyle (1980). Fifteen
      patients received clozapine; 7 received risperidone. Mean +/- SD age of the
      sample, comprising 12 men and 10 women (68% white), was 44.7 +/- 8.4 years. Mean
      +/- SD age at onset of schizophrenia illness was 23.5 +/- 7.4 years. Two
      anticholinergic assays based on blood samples collected 1 week apart were
      available on each patient. RESULTS: Data indicated that clozapine patients had
      significantly (p < .001) higher anticholinergic levels at both collection points,
      and levels for both drugs remained stable over time. The clozapine and
      risperidone patients had essentially equivalent scores on the cognitive measure.
      CONCLUSION: These data suggest that anticholinergicity distinguishes clozapine
      and risperidone in vivo but that this effect is not associated with differences
      in global cognitive functioning. Results suggest that clozapine, despite
      producing moderately high in vivo serum anticholinergic levels, still holds
      clinical advantage over standard neuroleptics in terms of cognitive side effects.
      Reasons for this lowered risk of cognitive impairment are discussed.

PMID- 9590670
TI  - Psychiatric hospital utilization in patients treated with clozapine for up to 4.5
      years in a state mental health care system.
AB  - OBJECTIVE: We wished to study long-term psychiatric hospital utilization in a
      large sample of patients with schizophrenia and/or schizoaffective disorders who
      were treated with clozapine for up to 4.5 years, and to determine whether or not
      the reduction in hospital utilization we previously observed in smaller groups
      for up to 2.5 years was sustained with larger groups and in the longer term.
      METHOD: Patients in Texas state hospitals who had schizophrenia and/or
      schizoaffective disorder took either clozapine or traditional antipsychotics for
      1.5 to 4.5 years. The number of patients in the clozapine group ranged from 383
      (1.5 years of treatment) to 29 (4.5 years). The group of patients who took
      traditional antipsychotics was made up of all patients (N = 233) with similar
      diagnoses, symptom severity, and duration of illness present in Texas state
      hospitals on an index day. RESULTS: The clozapine group showed a rapid and
      continuing decrease in hospital bed-days compared with controls who took
      traditional antipsychotics. The number of clozapine-treated patients who required
      little or no hospitalization during successive 6-month periods became significant
      (p < .0001) within 1.5 years, and continued to increase. Conversely, the number
      of patients taking clozapine who required virtually continuous state
      hospitalization decreased markedly compared with those taking traditional
      antipsychotics. CONCLUSION: Potential hospital cost savings are substantial, even
      though overall group results are diluted by clozapine nonresponders. Most
      treatment costs for clozapine nonresponders were related to hospital care; most
      or all of such costs would have been present in any event had these patients
      remained on traditional antipsychotic therapy. We believe a trial of clozapine
      therapy provides a low-cost opportunity for a highly effective and highly cost
      saving outcome in those patients who will favorably respond to this therapy. We
      discuss clinical, social, and economic advantages of modern pharmaceutical
      treatments over traditional drugs.

PMID- 9590672
TI  - Second thoughts about clozapine as a treatment for neuroleptic-induced akathisia.

PMID- 9590673
TI  - Clozapine-induced eosinophilia: subsequent neutropenia and corresponding allergic
      mechanisms.

PMID- 9590674
TI  - Schizophrenia and changes in physical appearance.

PMID- 9590675
TI  - Family history and early psychotogenic response to marijuana.

PMID- 9590676
TI  - Fluoxetine-induced genital anesthesia relieved by Ginkgo biloba extract.

PMID- 9590678
TI  - US seeks fair deal for biologists on synchrotron source access.

PMID- 9590677
TI  - DSM-IV intermittent explosive disorder: a report of 27 cases.
AB  - BACKGROUND: The authors' objective was to provide data regarding the demographic,
      phenomenological, course of illness, associated psychiatric and medical
      comorbidity, family history, and psychiatric treatment response characteristics
      of rigorously diagnosed subjects who met DSM-IV criteria for intermittent
      explosive disorder. METHOD: Twenty-seven subjects meeting DSM-IV criteria for a
      current or past history of intermittent explosive disorder were given structured
      diagnostic interviews. The subjects' medical histories, family histories of
      psychiatric disorders, and responses to psychiatric treatments were also
      assessed. RESULTS: Most subjects described their intermittent explosive disorder
      symptoms as very distressing and/or highly problematic. All 27 subjects described
      aggressive impulses prior to their aggressive acts. Of 24 subjects who were
      systematically queried, 21 (88%) experienced tension with the impulses; 18 (75%),
      relief with the aggressive acts; and 11 (48%), pleasure with the acts. Most
      subjects stated that their aggressive impulses and acts were also associated with
      affective symptoms, particularly changes in mood and energy level. Twenty-five
      (93%) subjects had lifetime DSM-IV diagnoses of mood disorders; 13 (48%),
      substance use disorders; 13 (48%), anxiety disorders; 6 (22%), eating disorders;
      and 12 (44%), an impulse-control disorder other than intermittent explosive
      disorder. Subjects also displayed high rates of comorbid migraine headaches.
      First-degree relatives displayed high rates of mood, substance use, and impulse
      control disorders. Twelve (60%) of 20 subjects receiving monotherapy with an
      antidepressant or a mood stabilizer reported moderate or marked reduction of
      their aggressive impulses and/or episodes. CONCLUSION: Intermittent explosive
      disorder appears to be a bona fide impulse-control disorder that may be related
      to mood disorder and may represent another form of affective spectrum disorder.

PMID- 9590679
TI  - Animal deaths turn shuttle into 'necrolab'.

PMID- 9590680
TI  - Bid to give legal protection to laboratory mice in US.

PMID- 9590681
TI  - It's Jakob's disease, not Creutzfeldt's.

PMID- 9590682
TI  - Membrane fusion. SNAREs line up in new environment.

PMID- 9590683
TI  - What killed the monk seals?

PMID- 9590684
TI  - Bacterial chemotaxis. United we sense...

PMID- 9590685
TI  - Hybrid genetics. Transposons unbound.

PMID- 9590686
TI  - Noticing Nature.

PMID- 9590687
TI  - Did algal toxins cause monk seal mortality?

PMID- 9590688
TI  - ATP synthase's second stalk comes into focus.

PMID- 9590689
TI  - New specimens and confirmation of an early age for Australopithecus anamensis.
AB  - The discovery of Australopithecus anamensis fossils from strata lying between
      tephra dated at 4.17 and 4.12 million years ago, and from slightly higher strata
      not well constrained in age by overlying dated units, provoked the claim that
      more than one species might be represented: it was suggested that the
      stratigraphically higher fossils, which include the important tibia, humerus and
      a large, presumed male, mandible (KNM-KP 29287), might belong to a later, more
      derived hominid. We have recovered new fossils from Kanapoi and Allia Bay, Kenya,
      during field work in 1995-1997 that confirm the primitive status of
      Australopithecus anamensis, the earliest species of Australopithecus. Isotope
      dating confirms A. anamensis' intermediate age as being between those of
      Ardipithecus ramidus and Australopithecus afarensis. New specimens of maxilla,
      mandible and capitate show that this species is demonstrably more primitive than
      A. afarensis. A lower first deciduous molar (dm 1) is intermediate in morphology
      between that reported for Ardipithecus ramidus and A. afarensis. Single-crystal
      40Ar-39Ar age determinations on the Kanapoi Tuff show that, except for a large
      mandible, all of the hominid fossils from Kanapoi are from sediments deposited
      between 4.17+/-0.03 and 4.07+/-0.02 million years ago.

PMID- 9590690
TI  - Undermethylation associated with retroelement activation and chromosome
      remodelling in an interspecific mammalian hybrid.
AB  - Genetic models predict that genomic rearrangement in hybrids can facilitate
      reproductive isolation and the formation of new species by preventing gene flow
      between the parent species and hybrid (sunflowers are an example). The mechanism
      underlying hybridization-induced chromosome remodelling is as yet unknown,
      although mobile element activity has been shown to be involved in DNA
      rearrangement in some dysgenic Drosophila hybrids. It has been proposed that DNA
      methylation evolved as a means of repressing the movement of mobile elements (the
      host defence model). If such a protective mechanism were to fail, mobile elements
      could be activated, and could cause major and rapid genome alterations. Here we
      demonstrate the occurrence of genome-wide undermethylation, retroviral element
      amplification and chromosome remodelling in an interspecific mammalian hybrid
      (Macropus eugenii x Wallabia bicolor). Atypically extended centromeres of
      Macropus eugenii derived autosomes in the hybrid were composed primarily of an
      unmethylated, amplified retroviral element not detectable in either parent
      species. These results, taken with the observation of deficient methylation and
      de novo chromosome change in other mammalian hybrids, indicate that the failure
      of DNA methylation and subsequent mobile-element activity in hybrids could
      facilitate rapid karyotypic evolution.

PMID- 9590691
TI  - Hypothalamic CART is a new anorectic peptide regulated by leptin.
AB  - The mammalian hypothalamus strongly influences ingestive behaviour through
      several different signalling molecules and receptor systems. Here we show that
      CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is
      a satiety factor and is closely associated with the actions of two important
      regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show
      a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus.
      In animal models of obesity with disrupted leptin signalling, CART mRNA is almost
      absent from the arcuate nucleus. Peripheral administration of leptin to obese
      mice stimulates CART mRNA expression. When injected intracerebroventricularly
      into rats, recombinant CART peptide inhibits both normal and starvation-induced
      feeding, and completely blocks the feeding response induced by neuropeptide Y. An
      antiserum against CART increases feeding in normal rats, indicating that CART may
      be an endogenous inhibitor of food intake in normal animals.

PMID- 9590692
TI  - Dramatic decreases in brain reward function during nicotine withdrawal.
AB  - Tobacco smoking is a worldwide public health problem. In the United States alone,
      over 400,000 deaths and $50 billion in medical costs annually are directly
      attributed to smoking. Accumulated evidence indicates that nicotine is the
      component of tobacco smoke that leads to addiction, but the means by which
      nicotine produces addiction remain unclear. Nicotine is less effective as a
      positive reinforcer than other drugs of abuse in non-dependent animals.
      Nevertheless, nicotine-withdrawal symptoms, including depressed mood, anxiety,
      irritability and craving in dependent subjects may contribute to the addictive
      liability of nicotine. We show here that spontaneous nicotine withdrawal in rats
      resulted in a significant decrease in brain reward function, as measured by
      elevations in brain reward thresholds, which persisted for four days. Further,
      systemic injections of a competitive nicotinic-receptor antagonist led to a dose
      dependent increase in brain reward thresholds in chronic nicotine-treated rats.
      The decreased function in brain reward systems during nicotine withdrawal is
      comparable in magnitude and duration to that of other major drugs of abuse, and
      may constitute an important motivational factor that contributes to craving,
      relapse and continued tobacco consumption in humans.

PMID- 9590693
TI  - Salmonella typhi uses CFTR to enter intestinal epithelial cells.
AB  - Homozygous mutations of the cystic fibrosis transmembrane conductance regulator
      (CFTR) cause cystic fibrosis (CF). In the heterozygous state, increased
      resistance to infectious diseases may maintain mutant CFTR alleles at high levels
      in selected populations. Here we investigate whether typhoid fever could be one
      such disease. The disease is initiated when Salmonella typhi enters
      gastrointestinal epithelial cells for submucosal translocation. We found that S.
      typhi, but not the related murine pathogen S. typhimurium, uses CFTR for entry
      into epithelial cells. Cells expressing wild-type CFTR internalized more S. typhi
      than isogenic cells expressing the most common CFTR mutation, a phenylalanine
      deleted at residue 508 (delta508). Monoclonal antibodies and synthetic peptides
      containing a sequence corresponding to the first predicted extracellular domain
      of CFTR inhibited uptake of S. typhi. Heterozygous deltaF508 Cftr mice
      translocated 86% fewer S. typhi into the gastrointestinal submucosa than wild
      type Cftr mice; no translocation occurred in deltaF508 Cftr homozygous mice. The
      Cftr genotype had no effect on the translocation of S. typhimurium.
      Immunoelectron microscopy revealed that more CFTR bound to S. typhi in the
      submucosa of Cftr wild-type mice than in deltaF508 heterozygous mice. We conclude
      that diminished levels of CFTR in heterozygotes may decrease susceptibility to
      typhoid fever.

PMID- 9590694
TI  - Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells.
AB  - Interleukin-6 (IL-6) is a cytokine that was initially recognized as a regulator
      of immune and inflammatory responses, but it also regulates the growth of many
      tumour cells, including prostrate carcinoma. Overexpression of the growth-factor
      receptors ErbB2/neu and ErbB3 has been implicated in the neoplastic
      transformation of prostate carcinoma. Here we show that treatment of the prostate
      cancer cell line LNCaP with IL-6 induces tyrosine phosphorylation of ErbB2 and
      ErbB3, but not ErbB1/EGFR. We also show that ErbB2 forms a complex with the gp130
      subunit of the IL-6 receptor in an IL-6-dependent manner. This association is
      important because the inhibition of ErbB2 activity results in abrogation of IL-6
      induced MAPK activation. Thus ErbB2 is a critical component of IL-6 signalling
      through the MAP kinase pathway. These data show how a cytokine receptor can
      diversify its signalling pathways by engaging with a growth-factor receptor
      kinase.

PMID- 9590695
TI  - Receptor clustering as a cellular mechanism to control sensitivity.
AB  - Chemotactic bacteria such as Escherichia coli can detect and respond to extremely
      low concentrations of attractants, concentrations of less than 5 nM in the case
      of aspartate. They also sense gradients of attractants extending over five orders
      of magnitude in concentration (up to 1 mM aspartate). Here we consider the
      possibility that this combination of sensitivity and range of response depends on
      the clustering of chemotactic receptors on the surface of the bacterium. We
      examine what will happen if ligand binding changes the activity of a receptor,
      propagating this change in activity to neighbouring receptors in a cluster.
      Calculations based on these assumptions show that sensitivity to extracellular
      ligands increases with the extent of spread of activity through an array of
      receptors, but that the range of concentrations over which the array works is
      severely diminished. However, a combination of low threshold of response and wide
      dynamic range can be attained if the cell has both clusters and single receptors
      on its surface, particularly if the extent of activity spread can adapt to
      external conditions. A mechanism of this kind can account quantitatively for the
      sensitivity and response range of E. coli to aspartate.

PMID- 9590696
TI  - Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex.
AB  - The assembly of transcriptional regulatory DNA sequences into chromatin plays a
      fundamental role in modulating gene expression. The promoter of the mouse mammary
      tumour virus (MMTV) is packaged into a regular array of nucleosomes when it
      becomes stably integrated into mammalian chromosomes, and has been used to
      investigate the relationship between chromatin architecture and transcriptional
      activation by the hormone-bound glucocorticoid and progesterone receptors. In
      mammalian cells that express both of these receptors, the progesterone receptor
      activates transcription from transiently transfected MMTV DNA but not from
      organized chromatin templates. Moreover, the activated progesterone receptor
      inhibits the chromatin remodelling and consequent transcriptional stimulation
      that is mediated by the glucocorticoid receptor. Here we investigate the
      mechanism of this inhibition by characterizing the interaction of the
      glucocorticoid receptor with transcriptional co-activator and chromatin
      remodelling protein complexes. We show that when this receptor is prevented from
      interacting with the hBRG1/BAF chromatin remodelling complex, it can activate
      transcription from transiently transfected DNA but not from organized chromatin
      templates. Our results indicate that it may be possible to separate the
      transcriptional activation and chromatin remodelling activities of proteins that
      interact with hormone receptors.

PMID- 9590697
TI  - Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins.
AB  - The Saccharomyces cerevisiae RAD51 and RAD54 genes are both required for the
      occurrence of homologous recombination and for the repair of double-stranded DNA
      breaks. Previous studies have indicated that Rad51 protein, together with the
      single-stranded DNA-binding factor replication protein A (RPA), can promote the
      formation of heteroduplex DNA, which is a key intermediate in homologous
      recombination. Here we report the purification of the Rad54 protein to near
      homogeneity and the biochemical testing of its molecular function. We find that
      Rad54 protein possesses a double-stranded DNA-dependent ATPase activity, and that
      it interacts with the Rad51 protein. Addition of Rad54 protein to reactions
      containing Rad51 strongly stimulates the rate of pairing between homologous
      single-stranded and double-stranded DNA molecules. We conclude that Rad54 acts to
      overcome kinetic impediments that would limit homologous DNA pairing between
      recombining chromosomes in vivo.

PMID- 9590698
TI  - Acute effects of distal pancreatectomy on portal and peripheral blood insulin
      concentrations in patients undergoing total gastrectomy.
AB  - The influence of distal pancreatectomy on portal and peripheral blood
      immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) concentrations was
      evaluated in patients undergoing total gastrectomy. There were 22 patients
      studied, 12 of whom did not undergo distal pancreatectomy (group 1), and 10 who
      did (group 2). In group 2, the increase in portal blood IRI concentrations after
      a glucose infusion of 25 g over 30 min was suppressed, and reelevation of the
      portal blood IRG concentration after the glucose-induced depression was inhibited
      compared to group 1. In contrast, the peripheral blood IRI concentration did not
      reflect these changes in the portal blood IRI concentration. The rise in the
      arterial ketone body ratio (AKBR) and the fall in the total ketone body
      concentration after glucose infusion were also attenuated after distal
      pancreatectomy in group 2. These findings suggest that distal pancreatectomy has
      an immediate suppressive effect on the pancreatic secretion of insulin and
      glucagon, and might disturb metabolism in the liver.

PMID- 9590699
TI  - Angiogenesis in poorly differentiated medullary carcinoma of the stomach.
AB  - We studied the role of angiogenesis in patients with medullary type poorly
      differentiated adenocarcinoma (MTPDA) of the stomach. Immunohistochemical
      analyses were conducted using antibodies against factor VIII (endothelial cells),
      vascular endothelial growth factor (VEGF) and its receptors (KDR andflt-1), and
      basic fibroblast growth factor (bFGF) and its receptors (bek andflg). Archival
      specimens of MTPDA (n=22) and non-MTPDA (n=47) were studied. The expression of
      VEGF and bFGF, the vessel count, and positivity of KDR on endothelium were all
      significantly higher in MTPDA than in non-MTPDA. The vessel count correlated with
      the VEGF expression in MTPDA. The vessel count and VEGF expression increased with
      the increasing stage of disease in MTPDA but not in non-MTPDA. The expression of
      bFGF and its receptors did not correlate with the vessel count and stage of
      disease in either type. These findings thus suggest that the biological behavior
      of medullary type poorly differentiated adenocarcinoma of the stomach is
      angiogenesis-dependent. The correlation of the VEGF expression and its
      endothelial receptors with the vessel count and the stage of disease thus
      suggests that VEGF is a factor responsible for the induction of angiogenesis in
      this type.

PMID- 9590700
TI  - Plasma D-dimer level in patients with colorectal cancer: its role as a tumor
      marker.
AB  - The purpose of this study was to explore the relationship between the
      preoperative plasma D-dimer (DD) levels and the tumor pathology of colorectal
      cancer. The plasma DD levels were measured preoperatively in 108 patients with
      colorectal cancer, and then were correlated with the tumor pathology and stage.
      The diagnostic value of the DD levels for the tumor stage was then compared with
      that of the preoperative carcinoembryonic antigen (CEA) levels. The preoperative
      DD levels were higher in patients with either a large-sized tumor or a tumor
      showing deep wall penetration. Lymph-node metastasis, lymphatic invasion, hepatic
      metastasis, and peritoneal dissemination were all associated with higher DD
      levels. A stepwise increase in the median DD level was found with the tumor
      stage. The preoperative DD levels also significantly correlated with CEA levels.
      When a cutoff value of 0.6 microg/ml was used in the DD assay, the sensitivity
      and specificity for Dukes C or D cancer were 67.2% and 64.0%, and those for Dukes
      D cancer were 91.3% and 57.6%, respectively. Although the DD assay was less
      specific, its diagnostic value in the preoperative staging of colorectal cancer
      was comparable to that of the CEA assay. The measurement of the preoperative DD
      level is thus considered to be useful for the preoperative staging of colorectal
      cancer.

PMID- 9590701
TI  - Quenching the effects of L-arginine on free radical injury in cultured
      cardiomyocytes.
AB  - Neutrophil activation and oxygen-derived free radical formation have been
      implicated in cardiac ischemia-reperfusion injury. To elucidate the mechanism of
      ischemia-reperfusion injury, we thus determined the effect of the nitric oxide
      (NO) precursor L-arginine on the free radical injury of cultured cardiomyocytes
      which were obtained from patients undergoing corrective surgery for tetralogy of
      Fallot. Free radicals were generated from hypoxanthine via xanthine oxidase, and
      the cellular changes were determined microscopically. All concentrations of L
      arginine (0.5 to 3 mM) prolonged the myocyte survival time compared to the
      control group, with 0.5 mM L-arginine increasing the survival time to the
      greatest extent. Cellular susceptibility to free radical injury was the lowest
      with 0.5 mM L-arginine. Further experiments were performed with 0.5 mM L-arginine
      plus 100 mM or 1000 mM of the NO synthase (NOS) inhibitor NG-nitro-L-arginine
      methylester (L-NAME) to determine whether or not the effects of L-arginine are
      mediated through the NO pathway. The survival time for the cells treated with a
      concentration of L-NAME was shorter than for the cells treated with 0.5 mM L
      arginine alone. These results suggest that L-arginine acts through the NO
      dependent pathway. In conclusion, our findings thus confirmed the quenching
      effects of NO on free radical injury in cultured cardiomyocytes.

PMID- 9590702
TI  - Detection of type III collagen fragments in specimens of abdominal aortic
      aneurysms.
AB  - The purpose of this study was to analyze the collagens in aortic aneurysm walls
      and to investigate the mechanism of the formation of calcified abdominal aortic
      aneurysms (AAAs). Collagens were extracted from human aneurysmal aortic walls
      obtained during surgery, and from human nonaneurysmal aortic walls obtained at
      autopsy, using pepsin-acetic acid digestion. Electrophoresis and immunoblotting
      were performed. Type III collagen was found to be reduced in the arteriosclerotic
      aneurysmal aortic walls. The alpha1 chain of type II collagen/alpha1 chain of
      type I collagen ratio was 0.35+/-0.11 in the aortic aneurysms and 0.68+/-0.11 in
      the nonaneurysmal aortic walls (P=0.0111). All the calcified aneurysms were
      associated with type III collagen fragments having molecular mass of
      approximately 70 kDa and 30 kDa as estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Thus, we concluded that AAAs with
      calcification may be caused by an abnormal degradation of type III collagen.

PMID- 9590703
TI  - Portal vein reconstruction with conventional polytetrafluoroethylene grafts: an
      experimental study in dogs.
AB  - The purpose of this study was to examine the short- and long-term performance of
      conventional polytetrafluoroethylene (PTFE) grafts for portal vein
      reconstruction. The grafts were placed as a portal vein replacement in 11 mongrel
      dogs. At 1 month and 6 months, the grafts were then retrieved and examined for
      patency, while also undergoing a pathological analysis. During the observation
      period (at 55 days), one dog died of an unknown cause with a patent graft. The
      patency rates of the other 10 grafts were 83% (5/6) at 1 month and 100% (4/4) at
      6 months. However, the neointima formation was incomplete even 6 months after
      implantation. In conclusion, although conventional PTFE grafts may be used as a
      synthetic alternative to autogenous vein grafts, every effort should be made to
      use autogenous vein grafts before considering conventional PTFE grafts.

PMID- 9590704
TI  - Gianturco stents for the venous system: a detailed pathological study.
AB  - This study was designed to examine the short-term performance of Gianturco stents
      placed in the venous system, in comparison with that of stents placed in the
      arterial system. Single-bodied modified Gianturco stents were surgically placed
      in six dogs (group 1), while in another six dogs, only exposure of the vessels
      was performed (group 2). Segments with an outer diameter 0.9 times smaller than
      those of the stents were targeted in the infrarenal inferior vena cava (IVC), the
      portal vein (PV), and the infrarenal abdominal aorta (AA). The animals were
      killed 4 weeks postoperatively for pathological analysis. All the segments were
      patent in both groups. Although the stents placed in the infrarenal IVC and PV
      were completely covered with neointima, those placed in the infrarenal AA were
      only partially covered. Furthermore, the venous stents were deeply embedded in
      the media, while the aortic stents remained in the intima. Medial hyperplasia
      occurred in the venous stents, while intimal hyperplasia occurred in the aortic
      stents. In conclusion, Gianturco stents placed in the IVC and PV performed better
      in the short term than the stents placed in the AA.

PMID- 9590705
TI  - Synovial sarcoma of the esophagus: report of a case.
AB  - Synovial sarcomas are exceedingly rare neoplasms of the digestive tract. We
      herein report a case of a synovial sarcoma occurring in the esophagus of a 20
      year-old man. He had a history of acute lymphocytic leukemia and had undergone
      aggressive chemotherapy between the ages of 4 and 8 years. The tumor, which was
      large and extended into the upper mediastinum, was successfully resected without
      an esophagectomy via the cervical approach. After postoperative radiation and
      chemotherapy, the patient remained healthy, without any evidence of disease 20
      months after the operation.

PMID- 9590706
TI  - Primary malignant melanoma of the esophagus associated with adenocarcinoma of the
      lung.
AB  - We herein report an extremely rare case of a 55-year-old Japanese woman with a
      primary malignant melanoma of the esophagus associated with adenocarcinoma of the
      lung. The patient was admitted to our hospital with a malignant melanoma of the
      lower esophagus. The chest X-ray and computed tomography (CT) findings revealed
      an incidental abnormal shadow in the left lung, which was diagnosed to be
      adenocarcinoma of the lung by means of a CT-guided needle biopsy. After
      administering systemic chemotherapy with dacarbazine (DTIC), vincristine sulfate
      (VCR), and nimustine hydrochloride (ACNU) plus interferon-beta, the esophageal
      tumor markedly decreased in size. Subsequently, the patient underwent a radical
      resection of both the malignant melanoma of the esophagus and lung cancer via a
      left thoracotomy and laparotomy.

PMID- 9590707
TI  - Subclavian arterio-esophageal fistula secondary to fish bone impaction: report of
      a case.
AB  - A 48-year-old Indian man swallowed a fish bone and presented 1 week later with
      dysphagia, following a single episode of fresh hematemesis. A barium swallow
      demonstrated a horizontal mucosal tear at the level of the aortic arch, and
      computed tomography (CT) showed mediastinal emphysema and a bleeding point medial
      to the left subclavian artery which appeared to be contained by a surrounding
      hematoma. Subsequently, he developed sudden massive hematemesis and collapsed.
      Despite emergency surgery, the patient died. At the postmortem examination, a 1.2
      cm fistula tract was found connecting the esophagus to the left subclavian
      artery. This case report emphasizes that a diagnosis of arterio-esophageal
      fistula should be considered if a patient presents with fresh hematemesis and a
      recent history of foreign body ingestion.

PMID- 9590708
TI  - Gastric outlet syndrome caused by a gallstone: report of a case.
AB  - An extremely unusual case of gastric outlet syndrome, otherwise known as
      Bouveret's syndrome, caused by a large gallstone impacted in the duodenum due to
      a cholecystoduodenal fistula (CDF), is described herein. Another large gallstone
      impacted in the CDF itself was also detected. As endoscopic extraction of the
      gallstone from the duodenum proved unsuccessful, and a laparotomy was required.
      Our patient, being 88 years old, is probably the oldest patient recorded in the
      literature of this syndrome. The methods of establishing a correct diagnosis by
      endoscopy and recent therapeutic strategies are discussed following the case
      report.

PMID- 9590710
TI  - Surgical treatment of a cardiac papillary fibroelastoma developing from the
      chordae of the tricuspid valve: report of a case.
AB  - Papillary fibroelastoma is a rare, benign cardiac tumor that can cause multiple
      emboli. We report herein a case of papillary fibroelastoma developing from the
      chordae of the tricuspid valve which was detected by echocardiography and
      confirmed by surgical resection. To our knowledge, this is only the fifth
      documented case of a tricuspid valve papillary fibroelastoma detected by
      echocardiography in a living patient.

PMID- 9590709
TI  - Colonic obstruction induced by plasma cell granuloma of the transverse colon:
      report of a case.
AB  - Plasma cell granuloma is mainly composed of reactive plasma cell proliferation,
      the origin of which is uncertain. Immunohistochemically, the plasma cells are
      characterized by a polyclonal nature, and must be distinguished from plasmacytoma
      which displays a monoclonal nature. This tumor is most commonly found in the lung
      and bronchus, but has rarely been described in the alimentary tract. We report
      herein a case of plasma cell granuloma of the transverse colon. A 71-year-old
      woman was admitted for lower abdominal pain with severe inflammation and anemia.
      Ultrasound examination and computed tomography showed an abdominal tumor. Barium
      enema revealed the tumor to be located in the transverse colon causing colonic
      obstruction. The resected tumor was spherical and mainly spread in the submucosal
      layer. Microscopically, the tumor consisted of severe infiltration of mature
      plasma cells within the spindle-shaped myofibroblasts. Immunohistochemical
      studies showed IgA, IgG, IgM, and kappa and lambda chains, and revealed a
      polyclonal nature of the plasma cells. Thus, a pathological diagnosis of plasma
      cell granuloma affecting the transverse colon was made. To the best of our
      knowledge, this is the first report of successful surgical resection of plasma
      cell granuloma of the colon.

PMID- 9590711
TI  - Antiphospholipid antibody syndrome in a case with redo coronary artery bypass
      grafting under cardiopulmonary bypass.
AB  - A patient who underwent redo coronary artery bypass grafting developed severe
      thrombocytopenia. A platelet transfusion caused recurrent hypotension and
      hypoxia. The patient status was complicated by a systemic thrombosis including
      coronary graft occlusion and central vein thrombosis. We found that the lupus
      anticoagulant, as well as other autoimmune antibodies, was positive only after
      the thrombotic episode developed. Even though the lupus anticoagulant returned to
      negative about 2 months after the episode of graft occlusion, the patient
      eventually died of heart failure.

PMID- 9590712
TI  - Mitral valve replacement in a patient with an extensively calcified mitral
      anulus: report of a case.
AB  - We report herein the case of a patient with chronic renal failure in whom mitral
      valve stenosis with extensive mitral anular calcification involving the entire
      anulus and leaflets was successfully treated surgically. Excision of both
      leaflets and partial resection of the anular calcification enabled the insertion
      of a 23-mm St. Jude Medical prosthetic valve. The technical difficulties involved
      with inserting the appropriate-sized prosthetic valve in a narrowed mitral anulus
      with heavy calcification are discussed following this case report.

PMID- 9590713
TI  - Mycotic abdominal aortic aneurysm associated with myelodysplastic syndrome (MDS):
      report of a case.
AB  - A 59-year-old man, who manifested lower back pain, was admitted with sepsis and
      disseminated intravascular coagulation (DIC). A computed tomographic scan showed
      a slight thickening of the abdominal aortic wall. A blood examination revealed
      pancytopenia. Myelodysplastic syndrome was diagnosed after bone marrow aspiration
      and a chromosome analysis. Sepsis due to a Staphylococcus aureus infection and
      DIC subsided after medical treatment; however, an aortobifemoral bypass was
      performed upon the detection of a localized rupture of a mycotic abdominal aortic
      aneurysm 1 month later. The patient is still alive 2 years after operation
      despite the presence of a hematological disorder.

PMID- 9590714
TI  - Rupture of the innominate artery following tracheostomy: report of a case.
AB  - A 23-year-old man underwent a tracheostomy. A massive hemorrhage from the
      tracheostomy site occurred 50 days later. An emergency operation was immediately
      performed and an erosion was noted on the innominate artery. The artery was
      divided and the hemorrhage was successfully stopped.

PMID- 9590715
TI  - A combination of preductal aortic coarctation and type B dissection: report of a
      case.
AB  - We present herein the case of a 39-year-old man found to have significant
      coarctation of the preductal aorta combined with a type B dissection, associated
      with Marfan's syndrome. This extremely rare pathological combination could be
      defined preoperatively only by a three-dimensional computed tomography scan. By
      means of selective cerebral perfusion, the coarctation was resected, and the
      total aortic arch was replaced with a Dacron graft.

PMID- 9590716
TI  - Internal thoracic artery malperfusion syndrome after bilateral internal thoracic
      artery grafting: report of a case.
AB  - A 58-year-old man with postinfarction unstable angina was referred to the
      Department of Cardiovascular Surgery at the Saiseikai Kitakami Hospital for
      urgent coronary revascularization. The bilateral internal thoracic arteries
      (ITAs) were subsequently utilized to revascularize the myocardium. The left
      anterior descending artery (LAD) was revascularized with the in situ right ITA
      and the obtuse marginal artery was revascularized with the in situ left ITA.
      Although he was successfully weaned from cardiopulmonary bypass, he collapsed
      hemodynamically 15 min later. Thus, he underwent supplementary vein bypass
      grafting to the distal LAD and the diagonal artery. Postoperatively, his course
      was uneventful, apart from the perioperative infarction, and a coronary
      arteriogram demonstrated patent bilateral ITAs and vein graft. This case report
      emphasizes the importance of early recognition of this rare syndrome and
      advocates surgical treatment consisting of supplementary vein grafting.

PMID- 9590718
TI  - Thoracoscopic enucleation of a submucosal bronchogenic cyst of the esophagus:
      report of two cases.
AB  - Thoracoscopic enucleation of a bronchogenic cyst of the esophagus was
      successfully performed in two cases. The first patient was a 26-year-old female
      complaining of dysphagia and retrosternal discomfort. The second patient was a 56
      year-old female complaining of retrosternal discomfort. A close examination
      revealed a cystic lesion compressing the esophagus in both cases. Three trocars
      were employed under general anesthesia. Thoracoscopy offering excellent
      visualization allowed us to perform a precise anatomical dissection between the
      muscle layer and the mucosa. Both patients recovered uneventfully and the
      symptoms disappeared postoperatively. Thoracoscopic surgery is thus considered to
      be beneficial for the treatment of a benign esophageal tumor because of the small
      chest wall entry, which might positively contribute to a favorable postoperative
      course.

PMID- 9590717
TI  - Primary aortoenteric fistula with a chronic isolated abdominal aortic dissection:
      report of a case.
AB  - A 47-year-old woman on long-term hemodialysis due to a chronic isolated abdominal
      aortic dissection was admitted to our department with severe abdominal pain. She
      had not suffered any hematemesis or melena. An emergency laparotomy revealed an
      abdominal aortic aneurysm with a diameter of 60mm, densely adhered to the ileum.
      An aortoenteric fistula manifesting as intramural rupture into the ileum was
      found after infrarenal abdominal aortic and bilateral common iliac cross
      clamping. The fistula on the ileac side was nontransmural, but that on the aortic
      side communicated with the pseudolumen of the abdominal aorta, and contained
      mural thrombus. The infrarenal abdominal aorta and bilateral common iliac
      arteries were replaced with a collagen-sealed woven Dacron bifurcated graft.
      Histological examination of the ileum in this portion showed intramural bleeding
      and xanthomatous granulation with foam cell infiltration in the thickened
      subserosa. While it is difficult to diagnose nonpenetrating aortoenteric fistula
      preoperatively, such a fistula must be considered in a patient with severe
      abdominal pain, for whom previous abdominal aortic surgery has been performed or
      when an abdominal aneurysm is observed. To our knowledge, no other case of an
      aortoenteric fistula presenting as an intramural rupture into the ileum in an
      isolated abdominal aortic dissection has ever been reported.

PMID- 9590719
TI  - Malignant thymoma with direct invasion into the peritoneal cavity: report of a
      case.
AB  - Extrathoracic invasions or metastases from thymomas are extremely rare. We
      describe herein the case of a patient with malignant thymoma which recurred three
      times during an 8-year period and invaded directly into the peritoneal cavity,
      involving the gastrointestinal tract. The huge thymoma was completely resected,
      along with the fornix of the stomach, the transverse colon, and the 8th, 9th, and
      10th ribs. Careful observation and multidisciplinary treatment against recurrent
      thymoma will be requisite for this patient, even though the tumor has been
      completely resected.

PMID- 9590720
TI  - Internal jugular vein malformation with mature adipose deposits in the
      mediastinum.
AB  - Anomalies of the internal jugular vein are uncommon and not frequently
      experienced. Either a fusiform or saccular dilatation of the veins has been
      termed phlebectasia by some investigators and venous aneurysm by others. In 1928
      Harris was the first to describe this condition using the term "congenital venous
      cyst." Relatively few cases of head and neck venous aneurysms have since been
      reported. We herein report a case of congenital internal jugular vein
      malformation while discussing both the diagnosis and pathology.

PMID- 9590721
TI  - Malignant fibrous histiocytoma originating from the chest wall: report of a case
      and collective review of cases.
AB  - Malignant fibrous histiocytomas occur principally as a mass of the extremities,
      abdominal cavity, or retroperitoneum in adults. However, they only rarely occur
      in the chest wall. A rare case of primary malignant fibrous histiocytoma
      originating from the chest wall is herein presented. The 36 previously reported
      cases are also reviewed. Of the 32 patients who underwent a resection as the
      initial treatment, 10 (31.3%) had a local recurrence. Of the 37 patients with
      this disease, 9 (25.0%) had subsequent metastases. The majority of the deaths
      (36.1%) from this disease occurred within the first 12 months. The patients who
      undergo surgical and adjuvant therapy must therefore be monitored carefully by
      frequent examinations.

PMID- 9590722
TI  - Pure clear cell papillary thyroid carcinoma with chronic thyroiditis: report of a
      case.
AB  - We herein report a case of pure clear cell papillary thyroid carcinoma, which is
      the first reported case in Japan. The tumors measured 1.0 x 0.9 and 0.7 x 0.4 cm
      in size. An ultrasonographical examination revealed hypoechoic irregular-shaped
      lesions with fine internal calcifications. No lymph node metastasis was observed
      in any of the surgical specimens. Distant metastasis had not been observed as of
      6 years after surgical treatment. The number of cases of pure clear cell
      papillary carcinoma reported so far are too few to clearly elucidate its
      characteristics; however, the ultrasonographical findings and biological behavior
      of this case were compatible with those of non-clear cell papillary thyroid
      carcinoma.

PMID- 9590723
TI  - Intraoperative radiation therapy for a patient with bulky disease of mesenteric
      non-Hodgkin's lymphoma.
AB  - A long survival is rarely observed in patients demonstrating recurrent malignant
      lymphoma with bulky disease because of the appearance of chemoresistant tumor
      cells after extensive chemotherapy, and moreover the presence of bulky disease
      has also been consistently associated with a poorer response rate and a shortened
      survival, due to the fact that tumor size is the most significant factor for the
      treatment of non-Hodgkin's lymphoma. We herein describe a case of a 53-year-old
      woman presenting with the chief complaint of abdominal fullness, who underwent
      intraoperative radiation therapy (IORT) for recurrent bulky non-Hodgkin's
      lymphoma in the mesenterium. The patient has had no evidence of tumor recurrence,
      based on the findings of regular abdominal computed tomographic scans, 60 months
      after initial chemotherapy and 28 months after IORT.

PMID- 9590725
TI  - A simple method to avoid contamination while performing an immediate
      mucocutaneous suture of the intestinal stoma.
AB  - We herein report a simple method using intestinal clamps to prevent
      intraoperative contamination during an immediate mucocutaneous suture of the
      intestinal stoma. Using this technique, a protruded intestinal stoma can be
      constructed reliably without soiling. The technique can be used both for
      constructing an end as well as a loop intestinal stoma.

PMID- 9590724
TI  - Differential responses of brain, liver, and muscle glycogen to opiates and
      surgical stress.
AB  - We examined the effects of intracerebroventricular (ICV) cannula implantation
      followed by the administration of morphine sulfate (MOR) and its metabolite,
      morphine-6-glucuronide (M6G), on the glycogen content of the brain, liver, and
      muscle. ICV cannulation resulted in nearly a 30% reduction in brain glycogen, and
      ICV MOR resulted in a 36% reduction in liver glycogen content compared to time
      matched controls, but it had no additional effect on either the brain or muscle
      glycogen content. ICV M6G showed a more significant reduction, to 50% of liver
      glycogen, but it had no effect on either brain or muscle glycogen. Neither IV MOR
      nor M6G produced any significant alteration in tissue glycogen content. These
      results indicate that the stress response associated with neurosurgery,
      especially the placement of the ICV cannula, is associated with a decrement in
      brain glycogen. The activation of opioid receptors in the brain results in
      enhanced hepatic glycogenolysis but has no additional effect on the brain
      glycogen content.

PMID- 9590726
TI  - Prevention and control of influenza: recommendations of the Advisory Committee on
      Immunization Practices (ACIP). Centers for Disease Control and Prevention.
AB  - These recommendations update information concerning the vaccine and antiviral
      agents available for controlling influenza during the 1998-99 influenza season
      (superseding MMWR 1997;46[No. RR-9:1-25]). The principal changes include a)
      information about the influenza virus strains included in the trivalent vaccine
      for 1998-99, b) more detailed information about influenza-associated rates of
      hospitalization, and c) updated information on the possible relationship between
      Guillain-Barre syndrome and influenza vaccination.

PMID- 9590727
TI  - [Current status and prospects of the study on bone induction and bone
      morphogenetic proteins].

PMID- 9590728
TI  - [An experimental study on BMP gene expression in vivo].
AB  - The authors inserted the full length BMP-1 cDNA into Xbal-treated pRc/RSV plasmid
      via ligation, resulting in construction of pRc/RSV/BMP-1 eukaryotic expression
      vector. The validity of the reconstructed vector was confirmed by the restriction
      map. Then more reconstructed plasmids were extracted. According to the general
      principle of gene therapy, 100 micrograms of pRc/RSV/BMP-1 plasmid was
      transferred into a Balb/c mouse quadriceps by implantation under anaesthesia
      respectively. After 3 weeks, the BMP gene expression was detected in the mouse
      muscles by histoimmunochemistry.

PMID- 9590729
TI  - [The experimental study on expression of BMP3 gene during fracture healing].
AB  - The role of BMP3 in fracture repair and its basic mechanisms at the molecular
      aspect has been studied. Fourty-eight New Zealand white rabbits with the
      fractures in the middle of bilateral radial shafts were used as animal models,
      and divided randomly into six groups for calluses at the 1st, 2nd, 3rd, 4th, 6th
      and 8th week after the onset of fracture. The levels and the cellular
      localizations of expression of BMP3 mRNA were investigated with the nucleotide
      hybridization techniques. The results revealed that BMP3 gene expression was
      highly increased in the early phase of fracture repair, and reached its peak at
      the second week (about 3.4-fold of that of the normal control). The strong
      expression of BMP3 gene was localized in mesenchymal cells, chondroblasts and
      osteoblasts. The results suggest that BMP3 plays an important role of bone
      induction in the early stage of fracture repair and it works by the way of
      autocrine or/and paracrine pathway.

PMID- 9590730
TI  - [The effect of implantation of reconstituted bone xenograft on the production of
      IL-2].
AB  - The present study is designed to investigate any possible effect of implantation
      of reconstituted bone xenograft (RBX) on the production of IL-2 by T-lymphocytes
      in female BALB/C mice model. IL-2 levels were elevated in all of the operated
      groups on the second day, suggesting a stress reaction to trauma caused by
      operative intervention rather than an immune response to RBX or bBMP. IL-2
      production declined significantly on the 7th (P < 0.05) and 14th days (P < 0.01)
      in RBX and bBMP groups, an evidence of inhibiting effect of RBX on the T
      lymphocyte function leading to lowered secretion of IL-2 by spleen T-cells in
      BALB/C mice. There was no significant difference in lowering of IL-2 secretion
      between the RBX and bBMP groups as seen when either was compared with the bCB
      group, suggesting an inhibiting action induced by BMP. The results demonstrated
      that RBX implantation was not associated with appreciable rejection in that
      activation, and proliferation of T-cells were inhibited and the secretion of
      cytokines was lowered resulting in suppressed cellular immunity. We are further
      convinced that RBX as an immuno-regulating cytokine possesses strong osteo
      inductive potential without evoking rejection.

PMID- 9590731
TI  - [An experimental study on the relationship between BMP's activity and its
      carrier].
AB  - To find out the relationship between human bone morphogenetic protein's activity
      and its carrier and to document the clinical application of BMP, we investigated
      six kinds of BMP carrier's influence upon hBMP's osteogenic activity with small
      sample size at first. Then three kinds of carriers selected from the six, added
      with the seventh carrier, were investigated with large sample size. The result
      showed that the compound of hBMP and hDDBM had best osteogenic ability. The human
      bone matrix had been formerly demineralized and extracted without hBMP. The hDDBM
      showed porous structure under SEM, its mean pore's diameter was 127 +/- 34
      microns. It was demonstrated that the function of demineralized bone matrix
      extracted without BMP (i.e. DDBM) was related not only to its pore's diameter,
      but to the fibrolike matter in it as well. With the method of BMP bioassay, BMP
      was composited with carrier, then the compound was injected into the calf of
      mouse. This made BMP's bioassay become simple and reliable.

PMID- 9590732
TI  - [Distribution and effectiveness of endogenic bone morphogenetic protein (BMP) in
      bone defect].
AB  - BMP is one of important factors in the pathophysiology of bone regeneration.
      Fifteen New Zealand rabbits were used in this experiment. We studied the
      distribution and effectiveness of endogenic BMP on a 10 mm bone defect of radius,
      by utilizing immunohistochemistry of BMP and quantitative computer imaging
      system. On the 3rd day, death of osteocytes and BMP positive blood clot were
      observed. The mesenchymal cells from periosteum and endoosteum, and osteoblast
      were also BMP positive. By quantitative study, we found there was a gradient
      distribution of BMP in bone defect, i.e, the value of BMP decreased gradually
      along the distance from the fracture ends. The maximal value of BMP was noted at
      the 1st week postoperation. In conclusion, two sources of endogenic BMP were
      found, one was from the absorption of necrotic tissue of fracture ends, the other
      was from the secretion of osteogenic mesenchymal cells during the process of bone
      regeneration. Nonunion of bone defect was caused in part by the gradient
      distribution of BMP. Accordingly, the concept of effective quantity of endogenic
      BMP was drawn rosen. It might be a new method in the treatment of bone defect by
      increasing the concentration of endogenic BMP and improving its distribution.

PMID- 9590733
TI  - [An experiment study of the guided bone regeneration].
AB  - During the process of wound healing, different cellular components have varied
      speeds of migrating. By implanting a membrane, a space was created for selected
      cells, that is so called guided tissue regeneration. Since bone had the potential
      of regeneration, the concept of guided tissue regeneration was used in the
      process of bone regeneration in the present study, namely, guided bone
      regeneration. Defects of 10 mm-long were produced on bilateral radii of 10 adult
      New Zealand rabbits by surgery. The defects on experimental sides were bridged
      with silicone tube. The opposite side served as the control. Radiography of
      forearms of rabbits was taken weekly. Samples were treated with 3-point bending
      test and histology respectively. On experimental sides, by 3-4 weeks, new bone
      from the fractured ends grew into bone defect, seven of ten healed within 6-8
      weeks. The other 2 only had a gap less than 1 mm left. No one healed on the
      control sides. The maximum value of 3-point bending test on experimental sides
      was 11.7 times greater than that of the control sides. It was shown that bone
      regenerated in the tube, and no callus formed out the tube by both gross samples
      and histologic examinations. On histology, the gap less than 1 mm on X-ray films
      was fibrocartilage zone, which connected regenerated bone from both distal and
      proximal bone ends. The defects on the control were occupied by connective
      tissue. In conclusion, guided bone regeneration also presents in long bone, that
      may provide a new method in the treatment of bone defect and promote fracture
      healing.

PMID- 9590734
TI  - [Function of bone morphogenetic protein in osteogenesis and its clinical use].

PMID- 9590735
TI  - [Traffic multiple trauma patient with head injuries: a study of 146 cases].
AB  - 146 cases of traffic multiple trauma associated with head injuries were studied.
      There was a significant difference in the ratio of associated injuries in various
      parts of the body. The three most encountered parts were chest, shoulder and leg.
      Death were mainly due to severe head injury, chest injury and shock. Atypical
      ushing syndrome was due to severe blood loss, even intracranial hypertension
      existed. The blood pressure decreased rapidly after operation. Since comatous
      patients were unable to provide chief complaint, misdiagnosis occurred during
      emergency stage.

PMID- 9590736
TI  - [Clinical application of soft-tissue flap with an intercostal vascular pedicle
      from the chest wall in the trachea surgery].
AB  - Between 1976 and 1995, 11 cases of side-wall defect repairment or circumferential
      reconstruction of trachea were performed using chest-wall tissue flap with an
      intercostal vascular pedicle. The indications were benign or malignant tumors of
      the tracheal side wall, lung cancers of the right upper lobe involving the side
      wall of the trachea and/or carina. The transverse diameter of the tracheal defect
      after removing the tumor was less than half of the tracheal circumference.
      Furthermore, we foun it feasible to reconstruct the trachea by using a tissue
      tube created by wrapping a chest-wall tissue flap over a temporary stent in case
      of long-segment tracheal resection of tracheal tumor or benign stenosis where.
      The defect was too long to be repaired by end-to-end anastomosis. The surgical
      technique & instructions were described.

PMID- 9590737
TI  - [Surgical treatment of aortoesophageal fistula induced by foreign body in
      esophagus].
AB  - It is well known that there is no effective therapy to cure aortoesophageal
      fistula induced by a foreign body in the esophagus all over the world. In 220
      cases of foreign body in esophagus, 4 developed the life-threatening complication
      of aortoesophageal fistula as the foreign body eroded through the esophageal wall
      and perforated the aorta. Although 3 of 4 patients were operated upon, only one
      survived by means of profound hypothermia and circulatory arrest. According to
      the successful experience and a review of the literature, the authors considered
      that some patients with aortoesophageal fistula may be saved if an emergency
      operation is undertaken immediately after the diagnosis made. Meanwhile, they
      divided this disease into 3 pathological types, and suggested the optimal
      operation procedure individualized to the different pathological types.

PMID- 9590738
TI  - [Expression and clinical significance of PCNA in renal pelvic and ureteral
      cancer].
AB  - To determine the relationship between PCNA expression and pathological stage,
      cellular grade, recurrence and prognosis of renal pelvic and ureteral cancer,
      research on PCNA proliferating index in 47 cases of renal pelvic and ureteral
      cancer we studied by immunohistochemistry S-P method. PCNA proliferating index of
      renal pelvic and ureteral cancer increased with pathologic stage and cellular
      grade. PCNA proliferating index of T3 + T4 was significantly higher than that of
      T1 + T2 (P < 0.01). PCNA proliferating index of G3 was significantly higher than
      that of G1 + G2 (P < 0.001). Those with higher PCNA proliferating index (III +
      IV) had higher bladder cancer recurrent rate after operation (60%, 12/20), those
      with lower PCNA proliferating index (I + II) had lower bladder cancer recurrent
      rate (22.2%, 6/27). P < 0.01. 35% (7/20) of those with III + IV PCNA
      proliferating index had simultaneous polyorganic urothalial cancer, 7.4% (2/27)
      of those with I + II PCNA proliferating index had simultaneous polyorganic
      urothelial cancer, P < 0.05. 7.4% (2/27) of those with I + II PCNA proliferating
      index had local recurrence and metastasis after operation, 40% (8/20) of those
      with III + IV had local recurrence and metastasis, P < 0.05. The 5-year survival
      rate of I + II was 86.7%, the 5-year survival rated of III + IV was 35.7% (5/14),
      P < 0.05. The findings suggest that PCNA proliferating index connects with
      pathological stage and cellular grade of renal pelvic and ureteral cancer. It is
      an important characteristic of low differentiation, invasiveness and simultaneous
      or sequentially polyorganic urothelial cancer. It may be an important prognostic
      indicator of renal pelvic and ureteral cancer.

PMID- 9590739
TI  - [Anti-reflux ureterocysto-reimplantation in treatment of ectopic ureters: report
      of 51 cases].
AB  - From 1974 to 1994, anti-reflux ureterocysto-reimplantation was performed on 51
      children (1 boy, 50 Girls) aged from 10 months to 13 years. The follow-up
      duration of 45 cases was 3 months to 14 years. The clinical symptoms of frequency
      of urination, lumbago and repeatedly fever, etc, were not observed except urinary
      incontinence in 2 cases. The results showed that ureterocysto-reimplantation is
      simple and traumatic. Some important aspects such as preoperative location and
      intraoperative identification of the unilateral or bilateral ectopic ureters were
      analyzed.

PMID- 9590740
TI  - [Proliferation and apoptosis status in benign prostatic hyperplasia].
AB  - The aim of this study was to examine the proliferation and apoptosis status in
      normal prostate and benign prostatic hyperplasia. The proliferation status was
      evaluated by using monoclonal antibodies which recognize the proliferating cell
      nuclear antigen and the proliferating associated nuclear antigen Ki67. The
      apoptosis status was detected by in situ end-labeling of fragmented DNA using the
      terminal deoxynucleotidyl transferase reaction. A total of 22 cases benign
      prostatic hyperplasia and 20 cases of normal protate specimens were studied. The
      proliferation index of BPH was much higher than that of normal prostates, and the
      apoptosis index of hyperplasia epithelium was much lower than that of normal
      prostatic epithelium. The results suggest that both high proliferating rate and
      low apoptosis rate are associated with the pathogenesis of benign prostatic
      hyperplasia.

PMID- 9590741
TI  - [Aspermia of epididymal blockage treated with epididymal tubule vasostomy].
AB  - To improve curative effect, we performed aspermia of epididymal blockage on 21
      patients with epididymal tubule vasostomy using microsurgical technique between
      1985 and 1994. In the 21 patients 20 showed sperm, and 18 increased sperm numbers
      over 4 x 10(7)/ml postoperation. The wives of 12 patients became reproductive.
      The selection of 3 different anastomotic ways using microsurgical technique could
      obviously improve curative effect, according to the dilated degree of epididymal
      tubule. The selection of anastomotic ways and liquid-passed test of deferential
      dust was also discussed.

PMID- 9590742
TI  - [Application of duplex color Doppler ultrasonography in the diagnosis of
      impotence].
AB  - High resolution of duplex color Doppler ultrasonography was used to evaluate 36
      cases of male impotence. The correlation between penile duplex sonography, penile
      brachial index (PBI), nocturnal penile tumescence (NPT), and penile
      cavernosography was studied. Penile duplex sonography was correlated with PBI and
      cavernosography.

PMID- 9590743
TI  - [The laboratory study on biofragmentable anastomosis rings (BAR) in
      gastrointestinal tract reconstruction].
AB  - To study and investigate the feasibility of biofragmentable anastomosis ring
      (BAR) for gastrointestinal (GI) tract reconstruction, we performed
      gastroenterostomy in 34 dogs. BAR anastomoses were performed with proper outer
      diameter and gape size in small bowel in 8 cases, in large bowel in 11 cases, in
      esophagus in 12 cases, in esophago-intestinal in 2 cases, in gastrojejunum in 1
      cases. The postoperative serial X-ray examinations showed that BAR maintained
      good integration two weeks postoperation. The ring disintegrated into several
      small fragments that passed out of the body in feces from the 14th postoperative
      day after surgery. All of the dogs were killed on the 28th operative day and
      autopsied. The anastomosis site had smooth serosa and scar membrane in gross and
      were substituted by regenerative fibrous tissue. The specimen barim-air double
      contrast X-ray revealed that GI tract was coherent without leakage and stenosis.
      Therefor, the authors recognized that BAR can be recommended as a safe technique
      in GI operation.

PMID- 9590744
TI  - [Calcification mechanism and anticaicification on cardial bioprostheses].
AB  - The high incidence of calcification in cardiac bioprostheses greatly shortens
      their service life. In this study, we found that the calcification of cardiac
      bioprostheses was related the content of free carboxyl groups in collagen
      molecule of cardiac bioprostheses. The method of chemical modification of
      glutaraldehyde (GA) treated cardiac bioprostheses with epoxy chloropropane (EC)
      was selected. The content of free carboryl groups in collagen molecule was
      reduced greatly in EC-modified valve tissues, and the calcified content of EC
      modified porcine aortic valve, bovine pericardial and porcine pericardial valves
      was reduced greatly at 2, 4, 6 weeks after subcutaneous implantation in young New
      Zealand rabbits. There were good physical stability, mechanical tensile strength
      and no immunologic reactions against the valve in EC modified valves. These
      findings showed that the anti-calcified valve can be used in clinic.

PMID- 9590745
TI  - [Changes of Kupffer cell DNA and RNA synthetic functions after partial
      hepatectomy in cirrhotic rats].
AB  - We studied the changes of DNA and RNA synthetic functions of regenerating liver
      cells after partial hepatectomy in cirrhotic rats and discussed the relationship
      between liver regeneration and liver functional failure. Seventy healthy male
      Wistar rats weighing 200 approximately 250 g, were randomized into sham-operated
      (SO), partial hepatectomy in cirrhotic rats (C-PH) and partial hepatectomy in
      normal rats (N-PH). The left and middle lobes were dissected. The synthetic DNA
      peak of Kupffer cells (KC) in the G2 and M phase in C-PH was found after 24 hr of
      operation. The regenerating index peak of KC was at 48 hr after operation, which
      was higher than the other groups, but the liver weights in C-PH was lower than
      that in the N-PH at 1 week after operation. The RNA content of KC markedly
      decreased and returned to normal levels at 1 week after operation. We think that
      KC functions are suppressed after partial hepatectomy in cirrhotic rats. It is an
      important cause of hepatocyte regeneration function decrease and liver functional
      failure for delay of liver cell regeneration "start" and the regeneration cell
      cycle.

PMID- 9590746
TI  - [Loss of p16 gene in bladder cancer and genitourinary carcinoma cell lines].
AB  - To determine whether p16, a novel antioncogene, is altered in human bladder
      cancer and urogenital carcinoma cell lines, we examined a series of 10 primary
      bladder cancer and 4 urogenital carcinoma cell lines (BIU-87, EJ, GRC and PC-3M)
      by southern blot. Two cases of 10 primary bladder cancer and EJ, BIU-87 PC-3M had
      homozygous deletion of p16, and 2 cases of 10 primary bladder cancer had loss of
      heterozygous. Loss of p16 may provide an additional growth advantage and
      carcinogenesis.

PMID- 9590747
TI  - [Relationship between the abnormal expression of CD44 gene and bladder cancer].
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot
      hybridization were used to detect exon V6-containing isoforms of CD44 gene in 42
      surgical bladder specimens (20 cases of bladder cancer, 10 cases of corresponding
      normal bladder tissue, 8 non-neoplastic bladder tissue from the benign prostatic
      hyperplasia, and 4 cystitis). All samples of bladder cancer tissue showed over
      expression of many abnormal alternatively-spliced products containing transcripts
      from exon V6 of the CD44 gene except those from 22 non-neoplastic tissue.
      Furthermore, the band pattern permitted differentiation between the 2 cases of
      metastatic bladder tumors and the 18 cases of non metastatic tissue. Our results
      suggest that there is a remarkable relationship between the abnormal CD44 gene
      expression (inappropriate splicing and overexpression) and malignant phenotype
      and metastasis of bladder cancer. The CD44 splice variants may prove to be a more
      ideal tumor marker for the early diagnosis of bladder cancer and for the early
      detection of metastatic potential in surgical biopsy specimens, which deserves
      further evaluation.

PMID- 9590748
TI  - [The relationship between p53 and PCNA in germ cell carcinoma].
AB  - To analyse the relationship between cellular proliferating status, p53
      expressions and tumor biological characteristics, immunohistochemistry was used
      in 13 cases of testicular germ cell carcinoma paraffin section. The results show
      that PCNA-LI is higher significantly in invasive tumor group than in noninvasive
      group (P < 0.05). Although there were no significant differences of PCNA-LI, p53
      between seminoma and nonseminoma, two parameters in the latter group were
      somewhat higher. There was a correlation of PCNA-LI with p53 in nonseminoma group
      (r = 0.64). It is concluded that PCNA-LI and p53 are both correlated positively
      with tumor differentiation.

PMID- 9590749
TI  - [Expression of basic fibroblast growth factor and its receptor in renal cell
      carcinoma].
AB  - Basic fibroblast growth factor (bFGF) is a pluripotent polypeptide which plays an
      important role in tumor progression and angiogensis. We determined the expression
      and localization patterns of bFGF and one of its receptor (FGFR-1) in normal
      renal as well as in renal cancers. The results were compared with
      clinicopathologic features. Using bFGF and FGFR-1 antibody, the repairing method
      of antigen with microwave oven heating and LSAB immunohistochemistry we used in
      36 cases of paraffin-embedded renal cell carcinoma (RCC) and their paired normal
      renal tissues. The expression of bFGF and FGFR-1 was nearly consistent. The
      normal renal tissues and ECM of 29 cases of renal cancer tissues showed
      heterogenous immunoreactivities. Renal cancer cell cytoplasm of 12 primary tumors
      and 2 metastatic tumors, as in the cytoplasmic bFGF of cultured GRC-1 cells, were
      positively homogenous stained. The bFGF and FGFR-1 can be consistently expressed
      in normal renal and renal cancer tissues, reflecting that the expression and
      function of these substances were closely associated. The cytoplasmic bFGF
      expression of renal cancer was related to tumor stages, suggesting that b bFGF
      plays an important role in the progression of renal cell carcinoma.

PMID- 9590750
TI  - [Primary epididymal tumors: report of 24 cases].
AB  - 24 cases of primary epididymal tumors including 23 benign and 1 malignant tumors
      were treated. In these cases, 66.7% situated at epididymal tail, and 12.5%
      involved both tail and body. Smooth muscle tumor of one case was bilateral, and
      adenomatoid tumor of another one was multiple. The symptoms of primary epididymal
      tumors were mild even absent, so the tumor was easily confused with non-tumorous
      mass of epididymis. Benign epididymal tumor should be differentiated from
      tuberculosis, chronic inflammation or granuloma. Besides signs of malignant mass,
      malignant epididymal tumor usually showed thickened spermatic cord, especially
      enlarged ductus deferens. The removal of the tumor mass or whole epididymis of
      the same side could cure benign epididymal tumor without recurrence. Malignant
      epididymal tumor should be treated as malignancy of testis or spermatic cord,
      with adjuvant chemotherapy or radiotherapy as indicated by the pathological type.

PMID- 9590751
TI  - [Surgical treatment of pulmonary metastasis from renal cancer: analysis of 9
      cases].
AB  - Nine patients with pulmonary metastasis from renal cancer were subjected to
      surgical treatment which included wedge resection (2 cases) and lobectomy (9).
      One case of multiple lesions in bilateral lungs was treated in the same time by
      cryosurgery and fulguration. The survival time after operation ranged from 5 to
      90 months. In this series, four cases are still alive, others survived for 13
      months, 20 months, 34 months, and 90 months, respectively. We suggest that the
      more active attitude should be taken for the surgical treatment of pulmonary
      metastasis.

PMID- 9590752
TI  - [Pericardial devascularization in the treatment of portal hypertension with
      Larjet's innervation].
AB  - From 1982, 48 cases of portal hypertension were treated by pericardral
      devascularization with Larjet's innervation. Results were compared with that
      without preserving the Larjet's nerve in 57 cases. The incidence of rebleeding,
      mortality, abdominal distension, diarrhea, and gastric retension was 2%, 6.3%,
      6.3%, 4.2%, and 0%, respectively in the former; and 12.5%, 12.3%, 24.6%, 15.6%,
      and 14%, respectively in the later. The authors believe that gastric function
      remained normal postoperatively when the Larjet's innervation was preserved.

PMID- 9590753
TI  - [Conservative treatment for early breast cancer].
AB  - 68 Cases of early breast cancer were divided into local resection group (33
      cases) and local resection plus axillary dissection group (35 cases). The 3-, 5-
      and 10-year survival rate of the two groups were 97.0%, 78.8%, 72.7% and 94.3%,
      80.0%, 77.1% respectively; The metastasis rate of the two groups were 6.1%,
      12.1%, 3.0% and 8.6%, 17.1%, 8.6% respectively; and the local recurrence rate of
      the two groups were 6.1%, 6.1%, 3.0%, and 5.7%, 5.7%, 2.9% respectively ( P >
      0.05). The cosmetic satisfaction rate of the two groups were 60.6% and 65.7%
      respectively ( P > 0.05). Factors relating to cosmetic results were type of
      breast, operative incision, age and postoperative radiotherapy. Conservative
      operation for early breast cancer was safe, provided incision margin was 2 cm
      approximately 3 cm. In all patients mammplasty was performed after tumor
      resection, and contralateral breast were treated by mammominification when it was
      necessary.

PMID- 9590754
TI  - [Anorectal malignant melanoma: report of 33 cases].
AB  - 33 Cases of anorectal malignant melanoma (ARMM) diagnosed pathologically were
      treated in Tianjin Cancer Hospital from 1996 to 1994. Some of these patients were
      treated with abdominoperineal resection (Mile's operation) and local resection
      plus chemotherapy, biotherapy and radiotherapy, others were given chemotherapy
      only. 25 cases were followed up from six months up to six years. The results
      showed that the median survival time was 23.5 months in the group of Mile's, 17.5
      months of local resection and 5.5 months in chemotherapy alone respectively. The
      authors considered that early diagnosis and treatment are the key to raise the
      survival rate. For the cases diagnosed pathologically the Mile's operation should
      be performed and groin dissection is necessary for cases of groin lymphatic
      metastasis.

PMID- 9590755
TI  - [Radical operation for Budd-Chiari syndrome under extracorporal circulation with
      deep hypothermia and circulatory pause].
AB  - The authors designed a new operation for the treatment of Budd-Chiari syndrome
      under deep hypothermia anesthesia with extracorporeal circulation, opening the
      superhepatic inferior vena cava (IVC) when the circulation was paused. Then the
      diseased focuses of IVC and HVs were resected under direct bloodless vision.
      After the incision of IVC was sutured, the normal circulation restored. From
      September 1993 to November 1995, 11 cases were treated in our hospital. All
      patients are well postoperatively, and followed up from 5 to 33 months.
      Ultrasonography revealed patent IVC and hepatic veins in all cases.

PMID- 9590756
TI  - [Early results of CABG operation in 110 patients].
AB  - Coronary artery bypass grafting (CABG) operations were performed in 110
      consecutive patients. Most of them had extensive triple-vessel disease or left
      main coronary artery disease. Internal mammary artery (IMA) was used as a graft
      in 65 patients. Valvular replacement or valvuloplasty were performed in 8
      patients and ventricular aneurysmectomy in 10 patients including post infarction
      VSD repaired in 1 patient simultaneously. Angina pectoris was relieved in all
      patients except one died from acute renal failure postoperatively. The IMA could
      be used safely and efficiently in nearly all patients. Using very fine technique,
      we suggested good exposure, and hemostasis to handle IMA. The key factor of
      success in CABG operation was complete revascularization by passing all
      significant stenosis larger than 1 mm diameter in all coronary artery branches.

PMID- 9590757
TI  - [Surgical treatment of primary epicardial tumors].
AB  - Seven cases of primary epicardial tumors of 3200 cardiac operation cases were
      diagnosed definitely, including benign in 5, malignant in 2. Among them, readical
      resection was performed in 5 cases, partial resection in 1, and decompression of
      pericardium in 1. Data of this series were often regarded as tuberculous
      pericarditis or others incorrectly. UCC, CT and MRI were helpful in diagnosis.
      The authors emphasize early surgical treatment as soon as possible and using the
      different methods of operation whether to utilize cardiopulmonary bypass or not
      according to site, size and characteristics of tumors to resect tumors, if
      necessary, reconstruction the heart wall to maintain blood follow dynamics. The
      prognosis of the diseases was related to the pathology and the area of invasion
      of tumors.

PMID- 9590758
TI  - [Early result comparison following mitral valve replacement with partial or
      entire subvalvular structure preservation].
AB  - 21 patients after mitral valve replacement with partial subvalvular structure
      preservation and 20 patients with entire subvalvular structure preservation were
      compared with 26 patients after mitral valve replacement with entire subvalvular
      structure excision. We found that patients after mitral valve replacement with
      partial or entire subvalvular structure preservation had a more uneventful
      postoperative course with less inotropic therapy and more decreased left atrial
      dimension when compared to those with conventional mitral valve replacement. But
      the patients after mitral valve replacement with entire mitral structure
      preservation had more decreased left ventricular dimension and short hospital
      stay when compared to those of the other two groups. The authors suggest that
      mitral subvalvular structure should be preserved, and we especially recommend the
      procedure of intravalvular implantation of mitral prosthesis with entire mitral
      subvalvular structure preservation.

PMID- 9590759
TI  - [Mitral valve replacement under beating heart in 137 cases].
AB  - To avoid damage of myocardial ischemia, myocardial hypoxia and reperfusion
      injury, we designed mitral valve replacement in beating heart under
      extracorporeal circulation with low dose temperature of 31 degrees C to 35
      degrees C in 137 cases of rheumatic heart disease, congenital heart disease
      mitral stenosis and mitral insufficiency, or concurrent aortic insufficiency. The
      patients were rept in unblocking aorta, unfilling cardiac arrest perfusion, idle
      pulse and dradycardia of 40-50 times/min, nose temperature of 32 +/- 1 degrees C.
      Patients with concurrent aortic insufficiency should first undergo replacement of
      aorta under cold cardiac arrest and then replacement mitral valve under beating
      heart to reduce the time of cold heart ischemia. Plastic surgery for tricuspid
      valve was done under beating heart. Good postoperative prognosis was nated: an
      average arterial pressure of 9.5-10.5 kPa (70 to 80 mmHg), dose of dopamine was
      obviously reduced. No low cardiac output syndrome, acute renal failure and severe
      arrythmia were observed in 137 cases, except 4 deaths due to infection and blood
      coagulation (2.9%). A left cardiac chamber no-level air removal device and aorta
      perfusioner leading flow device were designed for exsufflation of left
      pneumatocardia.

PMID- 9590760
TI  - [An experimental study on the anticancerous effects of CD3-TIL derived from human
      primary hepatic carcinoma].
AB  - In this study, CD3-TIL produced by in vito induction with CD3 and IL-2 (CD3-TIL)
      was compared with TIL stimulated by only IL-2 (TIL) in their in vitro
      proliferation, and both in vitro and in vivo anticancerous effects. It was found
      that CD3 at the concentration of 100 ng/ml was the most suitable stimulus of in
      vitro TIL proliferation (CD3-TIL) which was significantly greater than that by
      simple IL-2 stimulation. Also in vitro anticancerous activity of CD3-TIL was
      greater than TIL. CD3-TIL significantly inhibited tumor growth, causing shrinkage
      of tumor mass, and prolonging the life span of the nude mouse with tumor burden.

PMID- 9590761
TI  - [A study of mechanism by which tumor growth was induced by partial hepatectomy].
AB  - In this study, 18 BUF rats with 7316 A liver cancer burden were divided into
      three groups. Groups A underwent simple laparotomy, group B had 70% hepatectomy,
      and group C with laparotomy plus TGF-beta . Splenic adhesive cells and serum of
      postoperative day 5 in both group A and B were added into mixed lymphocellular
      culture and CCL-64 cell culture, TGF-beta was also added into MLC and 7613 A
      liver cancer culture. It was found that in group B and C the growth rate of tumor
      cells was greatly accelerated (P < 0.01); whereas MLC and CCL-64 cell
      proliferation was inhibited by the serum and splenic adhesive cells from group B
      (P < 0.05). TGF-beta also significantly inhibited MLC through it had no effect on
      7316 A liver cancer cells. The authors came to the conclusion that there was the
      activity of TGF-beta in the serum of the rats with partial hepatectomy which
      inhibits the proliferation of host immune cells.

PMID- 9590763
TI  - [Lung volume deduction surgery in the treatment of pulmonary emphysema].

PMID- 9590762
TI  - [Experimental studies of segmental bone defects treated by skeletal external
      fixation].
AB  - Bony tissue of an average of 13.6% of the original length (OL) was resected from
      the tibia shaft in 26 mature goats. The fracture ends were compressively fixed
      with skeletal external fixation (SEF). Simultaneously, upper metaphysiotomy was
      performed to lengthen the tibia with a lengthening rate of 1.0 mm/d and a total
      lengthening 20.14% of OL. The restoration of blood circulation and the
      hemodynamic changes during the repair process of the compressively fixed bone
      ends and the metaphysiotomy site were studied with angiography, microvascular
      cast, Chinese ink permeated transparent thick slide, and radioactive microsphere
      measurement of regional blood flow (RBF). It was found that there were abundant
      vascular networks in the lengthened zone. The blood vessels not only could keep
      up with the same lengthening rate of growing, but also were gradually converted
      into the Haversian system in the newly formed cortex of the lengthened area. In
      the 2nd week after the cessation of bone lengthening, the RBF of the lengthened
      zone reached the maximum (54.56 +/- 8.53 ml/mm/100 g). It was also found that in
      the 7th postoperative week, the vessels of the cortex of the osteotomy shortening
      ends could grow across the space between them and anastomose with each other. The
      RBF at this time was 31.82 +/- 2.85 ml/mm/100 g. In the 12th week after
      operation, the RBF was still 2 times higher than that of the normal cortex (3.02
      +/- 0.13 ml/mm/100 g). The primary healing could be observed under the
      wellreduction and stable compressive external fixation. These findings provide a
      theoretical basis for the clinical application of SEF for the treatment of tibial
      shaft defects or nonunion associated with limb shortening.

PMID- 9590764
TI  - [Clinical use of fibrin glue in orthopedics].

PMID- 9590765
TI  - [Surgical treatment of primary liver cancer].
AB  - The mortality rate of patients with primary liver cancer (PLC) was 20.40 per
      100,000 Chinese per year, that takes the second place among all forms of cancer.
      Surgical resection remains the modality of primary choice in the treatment of
      PLC. 2051 patients with PLC were treated by liver resection from 1960 to 1993. Of
      those, 94.1% were hepatocellular carcinoma (HCC) and the incidence of cirrhosis
      and chronic hepatitis was found in 86.5%. Small PLC (< or = 5 cm in diameter) was
      found in 25.1% of all cases. In the small PLC group, 176 cases were found the
      tumor < or = 3 cm in diameter. All 2051 patients received liver resection and
      44.0% of them had local radical resection. The overall mortality rate within one
      month after operation was 1.1%. The overall 5-year survival rate was 36.1%.
      Improved surgical result was obtained in 515 patients with small PLC (< or = 5 cm
      in diameter). No operative death occurred in this group and the 5-year survival
      rate was 79.8%. Moreover, the patients with very small PLC (< or = 3 cm in
      diameter) prolonged their survival. The 5-year survival rate was 85.3%. Early
      diagnosis and early resection of PLC are one of the key points for improving the
      long-term results. Improvements in operative techniques play an important role in
      reducing post-operative complications, lowering operative mortality and obtaining
      better operative results. Rehepatectomy for recurrent liver cancer can improve
      the surgical results. 95 patients underwent rehepatectomy with a 5-year survival
      rate of 53.2% and 25.0% after the first and second operation respectively. One
      patient survived 18 years. For unresectable large tumors, two-stage resection can
      be used. We collected 659 cases of large unresectable tumors from 1974 to 1994.
      Among them, 73 cases were resected in two-stage operation. The resection rate was
      11.1%, and the 5-year survival rate was 61.5%. Postoperative comprehensive
      treatment is also important for upregulating cellular immunological function,
      preventing tumor recurrence, and improving surgical results.

PMID- 9590766
TI  - [Application of CO2 enhanced ultrasound for two-stage operation of hepatic
      tumors].
AB  - The feasibility of CO2 enhanced ultrasound (CO2-EUS) was evaluated in two-stage
      operation patients with hepatic tumors. CO2-EUS was carried out in nine patients
      with indwelling catheter within hepatic artery for two-stage operation of liver
      cancer. CO2 microbubbles mixing by 5 ml of 5% NaHCO3 and 2.5 ml of 5% Vitamine C
      were injected into the indwelling catheter. The computed sonography of ACUSON
      128XP/10 with a 3.5 MHz convex transducer was used for this study. The enhanced
      parenchyma of the liver obtained by CO2-EUS and the lasting time of enhancement
      was about 8 minutes. The hepatic tumors, after chemotherapeutic treatment via
      indwelling catheter, were variously enhanced by CO2 microbubbles. The enhanced
      sonogram of the tumors took the forms of hypoechoic, ring-like, or spotty
      enhanced pattern lasting for more than 30 minutes. The margin of the enhanced
      tumors was very clear in CO2-EUS. CO2-EUS detected five more lesions (size 1-3
      cm) besides 9 lesions by conventional ultrasound. CO2-EUS was extremely useful in
      evaluating curative effects of tumor, increasing detection rates of small tumor,
      and improving thoroughness of two-stage operation.

PMID- 9590767
TI  - [Hepatic tuberculosis: a report of 8 patients].
AB  - 8 patients with hepatic tuberculosis were confirmed by surgical operation and
      pathological examination of liver. The average age of the patients was 26.5
      years. Only one of the 8 patients was suspected of having hepatic tuberculosis
      before operation. Liver biopsy during the operation was carried out in 3
      patients, and lobectomy or partial excision of the liver was performed in 4
      patients, and incision and drainage of the liver abscess were performed in 1
      patient. All of the patients were cured. The follow-up results showed that
      hepatic tuberculosis less than or equals to 3 cm in diameter could be cured by
      regular chemotherapeutics. In this paper, the infectious path, pathological
      types, differential diagnosis and treatment are discussed, and experience and
      lessons are summarized.

PMID- 9590768
TI  - [Re-operation of 136 recurrent cases of colorectal cancer].
AB  - We analyed 136 recurrent colorectal cancer cases their recurrence, residual
      cancer foci, extraintestinal infiltration, and inappropriate pelvic resection in
      patients receiving mile's procedure. The authors suggest that distal safe margin
      of the colon should at least be more than 3 cm and thorough dissection of the
      proximal third grade lymphonodes at the upper root of the mesentery and the
      lateral lymphonodes. For these 136 recurrent cases, after preoperative
      comprehensive procedure including intraarterial chemoembolization, radiation
      adjuvant immunotherapy, the resection rate of the recurrent mass was 84.5%. The
      five year survival rate of palliative resection was 40% as compared with 44.8% in
      radical resection.

PMID- 9590769
TI  - [Diagnosis and treatment of iatrogenic ureteral injury].
AB  - Diagnosis and treatment of 17 patients who sustained 20 iatrogenic ureteral
      injuries were analyzed. Primary operations in which ureteral injury occurred are
      almost gynecologic procedures and general surgery. Injuries were managed by
      ureteroureterostomy in four, ureteral stent in one, removal suture ligation and
      ureteral double J-catheter in one, ureteroneocystostomy in ten, psoas-hitch
      technique and ureteroneocystostomy in one, nephrectomy in two. All patients with
      appropriate repair were followed-up periods of three to five years. Renal
      function of these patients had optimal results. When ureteral injury occurs, B
      US, IVU, cystoscopy, retrograde ureterography or infusion of dye may be useful.
      An appropriate repair should be chosen according to length and position of
      ureteral injuries. Reoperation was optimal in two to three weeks. Immediate
      recognition of accidental ureteral injury provides optimal results. Patients with
      unrecognized injuries had suboptimal results.

PMID- 9590770
TI  - [Allotransplantation of fetal adrenal capsules for treating steroid deficiency].
AB  - A man suffering from bilateral adrenal carcinoma was treated by total
      adrenalectomy and steroids substitution. One and a half months later, two fetal
      adrenal capsules were grafted to his greater omentum. No immunosuppressive agent
      was given. From the fourth month exogenous steroid dose was gradually reduced.
      Five months after transplantation, substitution therapy was discontinued. The
      patient showed no signs of steroid deficiency and all laboratory studies were
      normal. Seven months later, the patient died of metastasis of the carcinoma.
      Pathological examination showed that much adrenal cortex had regenerated in the
      greater omentum. The findings suggest that this method for treating chronic
      steroid deficiency is simple and successful.

PMID- 9590771
TI  - [The postoperative effects of tapered terminal ileal continent urinary
      reservoir].
AB  - We report postoperative effects of 23 cases having tapered terminal ileal
      continent urinary reservoir is reported. The operative technique was
      characterized by tapering the terminal ileum with stapler to form a continent
      efferent tract, segments of intestine were cut open and reformed a pouch, and the
      ureter implantation was performed by means of inserting the end of ureters into
      the pouch. Ileocolonic pouch wes constructed for 14 patients and colonic pouch
      for 9 patients. 22 patients were followed up for 1 to 6 years except one died of
      cerebral hemorrhage 2 weeks after operation. Urine continence were achieved in
      all patients and self catheterization could be easily undertaken with 20F-22F
      catheter in 21. Difficulty in catheterization was happened in one early case. One
      year after operation, the maximum volume of the ileocolonic pouch was 900 ml-1000
      ml. The basal and intermittent pressure of the filling pouch was 0.49 kPa-1.96
      kPa respectively. The maximum volume of the colonic pouch was 400 ml-500 ml. The
      basal and intermittent pressure of the filling pouch of the colonic pouch was
      0.98 kPa-1.9 6 kPa and 1.96 kPa-3.93 kPa respectively. The complication of pouch
      overdistention was found in 6 cases, pouch stone formation in 2 and pouch
      infection in 12 episodes. There was no evidence of ureteral obstruction or reflux
      and significant hyperchloric acidosis. It is recognized that tapered terminal
      ileum is a good way to construct a continent efferent tract, both ileocolonic
      pouch and colonic pouch can meet the need of low inner pouch pressure so long as
      the intestines were cut open and reformed, and efforts must be made to prevent
      the complications of pouch overdistension, stone formation and pouch infection.

PMID- 9590772
TI  - [Translabyrinthine--transtentorial approach for removal of large acoustic
      neuromas].
AB  - In 30 consecutive patients with large acoustic neuromas, which were more than 4.0
      cm in diameter, tumor excision was performed by a one-stage combined
      translabyrinthine-transtentorial approach. The tumors were totally removed in 29
      patients (96.7%), without death. The facial nerve was preserved anatomically in
      16 patients (53.3%), and functionally in 11 (36.7%). Main advantages of this
      approach include: (1) direct approach with a more extensive exposure; (2)
      identification of both the origin of the facial nerve at the brain stem or in the
      internal auditory canal: (3) minimal postoperative reaction; (4) combination with
      other approaches. A brief discussion is been made on operative technique,
      prevention of postoperative complications and facial nerve preservation.

PMID- 9590773
TI  - [Intramedullary spinal teratoma].
AB  - We treated 5 cases of intradullary spinal teratomas from 1974 to 1995, accounting
      0.636% of all intraspinal tumors and 45.45% of all teratomas of spinal cord
      admitted in the same time. The origin of this tumor is controversial. It is not
      easy to differentiate this tumors from other intramedullary spinal tumors on
      clinical grounds. CT and MR scans of this tumor enabled us to make the
      preoperative diagnosis of teratoma. Resection is the only treatment of choice.

PMID- 9590774
TI  - [Clinical analysis of diagnosis and treatment of 44 cases with intraspinal
      lipoma].
AB  - 44 cases of intraspinal lipoma were confirmed by pathologic examination. We
      excised the lipomas totally or partly. After surgery, 8 cases improved greatly,
      19 cases improved, 18 not improved. CT scan and MRI are the key methods for
      diagnosis of intraspinal lipoma, most of intraspinal lipomas are adherent to the
      spine and root of nerves tightly and difficult to be dissected. So it's not easy
      to excise the lipoma entirely. But if we use microsurgery we can get better
      results.

PMID- 9590775
TI  - [Clinical treatment of post-thrombotic deep veins of lower limbs].
AB  - From 1989 to 1995, 213 patients with chronic post-thrombotic syndrome of the deep
      veins of lower limbs were treated. The surgical approaches consisted of
      establishment of temporary distal arteriovenous fistula for iliac and iliofemoral
      occlusion, and bypass of suitable length of autogenous vein with temporary distal
      arteriovenous fistula. Those who were not candidates for surgery were treated
      continuously by conservative methods with periodical short-term thrombolysis. A
      mean follow-up of 37.3 months the cure rate and the effective rate were 50.9% and
      83.5% respectively. The authors suggest that different methods may be used in
      different patients, and the temporary distal arteriovenous fistula is a new
      approach of the posthrombotic legs.

PMID- 9590776
TI  - [A randomized controlled clinical trial of sulperazon in the treatment of
      surgical infection].
AB  - Randomized controlled clinical study of Sulperazon (Sulbactam/Cefoperazon) was
      made in the surgical field. 35 cases were treated with Sulperazon and 32 cases
      with Ceftazidime. In the Sulperazon group (35 patients), the effective rate was
      88.6% as compared with 90.6% of the patients in the Ceftazidime group (32
      patients) (P > 0.05). The bacterial eradication rate was 86.2% in the Sulperazon
      group as compared with 88.5% in the Ceftazidime group. No significant difference
      was noted in both groups. In the Sulperazon group, side effects were not observed
      except nausea in one case.

PMID- 9590777
TI  - [DNA quantitative analysis of small bowel carcinoma and its clinical
      significance].
AB  - By using computer cytophotometric analysis, aneuploid as well as other 12
      parameters of tissue DNA content were measured in 28 cases of small bowel cancer,
      5 cases of intestinal adenoma, 6 cases of normal intestinal tissues. The number
      of aneuploid tumors in intestinal cancer was much higher than in intestinal
      adenoma. 7 DNA parameters (Entropy of DNA, 2CDI, DNA- grade of neoplasia, 5C
      Exceeding Rate, 9C Exceeding Rate, Diploid Deviation Quotient and Mean Ploidy)
      were the valuable indexes that could determine the quality of intestinal lesions,
      benign or malignant. DNA content didn't correlate with the clinically
      differentiated degree of pathological tissues, but aneuploid intestinal cancers
      had a higher malignant degree than non-aneuploid ones, and were more liable to
      invade and metastasize with low postoperative survival-rate and poor prognosis. 5
      DNA parameters (DNA-Index, Medal Value, DNA-grade of neoplasia, Stemline Ploid
      and 9C Exceeding Rate) had close relation to the prognosis of intestinal cancer,
      possessing important value to the prognostic analysis of intestinal cancer.

PMID- 9590778
TI  - [In situ hybridization to detect the mRNA for insulin-like growth factor-I and II
      in the prostate].
AB  - In order to well understand the expression of mRNA for insulin-like growth factor
      I and II in normal and hyperplastic prostate, in situ hybridization were used to
      detect them in a total of 35 cases of prostate. Both the normal and the
      hyperplastic prostate expressed the mRNA for IGF-I/II. The mRNA for IGF-I was
      mainly expressed by the epithelial cells and the IGF-II was mainly expressed by
      the stromal cells. The hyperplastic tissues expressed higher levels of the mRNA
      for IGF-I and IGF-II. The results suggested that the IGF might play an important
      role in the regulation of prostate growth and the pathogenesis of benign
      prostatic hyperplasia.

PMID- 9590779
TI  - [Preliminary study of colloid osmotic pressure for cardiopulmonary bypass].
AB  - The ideal colloid osmotic pressure is beneficial to decrease the fluid
      accumulated in the pulmonary and other tissue during cardiopulmonary bypass.
      Schupbach reported the proper colloidosmotic pressure for cardiopulmonary bypass
      was 2.1 kPa (16 mmHg). Colloid osmotic pressures of blood and priming fluid
      during cardiopulmonary bypass were measured in 28 patients with heart disease by
      using colloid osmotic pressure detection apparatus. The value of colloid osmotic
      pressure suitable for the designed standard was apparently different among the
      Gelofusine group and other groups. P value was 0.005. Priming fluid for
      cardiopulmonary bypass needs to satisfy the quality and the quantity of colloid
      osmotic pressure. Using Albumin isn't economical. Whole blood and plazma are not
      suitable for increasing colloid osmotic pressure. Hydroxyethyl starch or
      Gelofusine is best choice in priming to get designed standard of colloid osmotic
      pressure. The ratio of hydroxyethyl starch or Gelofusine in priming fluid should
      beyond 1/2.

PMID- 9590780
TI  - [The study of the morphology of ultramicrostructure in molecular level of nucleus
      herniation of lumbar intervertebral disc].
AB  - In order to investigate the morphology of ultramicrostructure in molecular level
      of nucleus herniations, the authors studied the ultramicrostructure of three
      cases of nucleus herniations of lumbar intervertebral disc which were proved by
      operations and one case of normal nucleus pulposus of fresh corpse by using of
      atomic force microscope. The results showed that the arrangement of collagen
      bundle, collagen fiber and procollagen fiber were different between the two
      conditions, and the morphology of molecular particles of proteoglycan in nucleus
      herniations was different from that in the normal condition. In the condition of
      nucleus herniations, the collagen fiber formed procollagen fiber reticular porous
      adhering to the molecules of protein and proteoglycan, and the DNA adhering to
      the monochain of RNA in fiberal cell nuclei, in the form of bichain and
      multichain three dimensions helix structures. The banded structure (64-78 mm) of
      the procollagen fiber, and the collagenation and calcification of the degenerated
      nuclens pulposuses, the quantity of which was significant greater than normal (P
      < 0.05) indicated that the chronic injury of lumbar intervertebral nucleus
      pulposuses gave rise to the injury and break of the collagen fiber which resulted
      in twist (tangle) phenomenon so that nucleus pulposuses lost their normal
      resistance strength.

PMID- 9590781
TI  - [Experimental research of the influences on the development of the hip joints
      with excavated acetabula].
AB  - There are still arguments about the operation excavated acetabula treatments for
      the congenital dislocation of the hip. To inquire into the influences on the
      development of the hip joints with excavated acetabula size, we divided 60 two
      month-old chickens into three groups which were given incised dislocation and
      then reduction partly excavated the cartilages of the acetabula and excavated
      them totally to the left hips respectively. Contrasting observation of all the
      experimental chickens was taken on the right ones of their own. The second group
      achieved a fair function of the joint movement. Limited and slight adhesion was
      not affecting the development of the joints seriously. The third group had, on
      the contrary, poor functions because of the comprehensive adhesion in the
      acetabula. The surfaces of the acetabula were replaced by fabric tissue. The
      remaining or regenerating cartilage cells vary obviously under the light scope
      and the electronic scope. The heads of the femurs had changed similarly. It is
      suggested that in dealing with the congenital dislocation of the hip, excavating
      the acetabola cartilage is not advisable. Partly excavating is permitted when a
      limited bony process existing in the bottom of the acetabula.

PMID- 9590782
TI  - [Modified duodenum-preserving resection of the head of the pancreas].
AB  - A modified procedure of duodenum-preserving resection of the head of the pancreas
      was used in treating three patients with benign lesions in the head of the
      pancreas. Compared with Beger's procedure, the modified procedure was simpler,
      and pancreaticojejunostomy on duodenal side was not necessary because of less
      remaining pancreas attached to the conjunction of the pancreatobiliary duct. The
      patients, recovered and ate food from 4 to 6 days after operation without
      symptoms of duodenal obstruction. The patient's digestive function was normal,
      and the pre- and postoperative pancreatic endocrine function was almost
      identical. This procedure can be used as the first-choice surgical procedure for
      benign lesions in the head of the pancreas. Problems in how to protect blood
      supply of the duodenum were also discussed.

PMID- 9590783
TI  - [Wear debris and late looseness of the prosthesis after total hip replacement].

PMID- 9590785
TI  - [Surgical treatment of juxta-renal abdominal aortic occlusion: report of 27
      cases].
AB  - Juxta-renal abdominal aortic occlusion is a relatively rare disease. We have
      treated 27 patients (25 males and 2 females) since 1984. Operations were
      performed on 25 patients, of whom 4 died and 84% improved. The main etiology was
      aorto-iliac stenosis or occlusion due to atherosclerosis and Takayasu's
      arteritis. Diagnostic basis included ischemia of lower limbs, pulselessness of
      abdominal aorta and both femoral arteries, sexual dysfunction, and positive
      result of angiography. Effective control of aorta below the left renal vein,
      aortotomy and retrograde endarterectomy were the main operative procedures.
      Axillo-bifemoral arterial bypass is recommended for patients associated with
      multiple diseases. The operative result is determined by associated diseases and
      the condition of run-off vessel. Associated diseases directly affect the
      mortality rate.

PMID- 9590786
TI  - [Angioscopic in-situ arterial bypass for lower extremity revascularization].
AB  - The authors' initial experience of angioscopic in-situ arterial bypass of 37
      extremities reveals that angioscopy can be used to assist complete valvular
      ablation and precise location and ligation of tributaries of saphenous vein
      grafts, avoiding postoperative arterial-venous fistula and warm ischemic injury
      to grafts. Angioscopy is also used to perform intraoperative completion
      inspection of the grafts and anastomoses. The designed biocomposite graft and
      common ostium technique promotes the usage rate of the limited autogenous vein
      grafts and enlarges the diameter of grafts and blood flow through the distal
      anastomosis. Because of the above new series of procedures, the extremity salvage
      rate in this study was 34/37 limbs. During the follow-up period of 2-18 months,
      all anastomoses were patent. The preoperative ankle and toe pressure of 3.5 +/-
      0.2 kPa and 2.0 +/- 0.1 kPa respectively rose to 5.4 +/- 0.1 kPa and 3.8 +/- 0.2
      kPa postoperatively. We conclude that angioscopic in-situ arterial bypass surgery
      is of practical value and specially advantageous in lower extremity
      revascularization.

PMID- 9590787
TI  - [Selection of surgical approaches in the treatment of aortoiliac arterial
      occlusive disease].
AB  - 31 patients with aortoiliac occlusive disease with or without infrainguinal
      occlusion was treated with thromboendarterectomies, aortoiliac or aortofemoral
      arterial bypasses, extra-anatomic bypasses and sequential arterial bypasses in
      the past 5 years. The results were satisfactory. The surgical mortality was 3.2%,
      the primary 5-year patent rate was 84.2%, and the secondary 5-year patent rate
      was 96.5%. We emphasize the value of ABI to indicate arterial reconstruction.

PMID- 9590788
TI  - [Thrombogenic cause of low extremity veins in patients undergoing pelvic
      operation].
AB  - Postoperative fatal pulmonary embolism caused thrombi from low extremity deep
      veins of patients after abdominal operation remains a major cause of death. Blood
      biorheology in 34 patients having pelvic operation and 41 patients having non
      pelvic operation was studied. Blood viscosity was significantly higher in pelvic
      operation than in non-pelvic operation. The low extremity venous blood viscosity
      was significantly higher than the upper extremity venous blood viscosity. These
      suggest that hyperviscosity status and hypercogulable of low extremity veins may
      be an important cause that deep venous thrombogensis occurs prone to the low
      extremities in patients with pelvic operation.

PMID- 9590789
TI  - [Interventional treatment for partial stenosis or occlusion type of Budd-Chiari
      syndrome].
AB  - It is difficult to deal with interventional management of partial stenosis or
      occlusion type of Budd-chiari syndrome and manage the hepatic veins associated
      with inferior vena cave occlusion. Puncture, PTA and vascular stent plant were
      used to treat 12 patients with partial stenosis or occlusion of Budd-chiari
      syndrome. The procedures were successful. Either the symptoms or signs
      disappeared or relieved after operation. No severe side effects occurred. Follow
      up for 1.5 through 26 months (average 8.5 months) revealed that the early or
      middle results were gratifying. There may be danger during operation, but perfect
      skills and adequate clinical anatomic knowledge help avoid severe side effects.

PMID- 9590790
TI  - [Clinical evaluation of Doppler ultrasonic angiography].
AB  - The diagnosis of carotid surgery is based on angiography. 1607 Doppler cases of
      extracranial carotid Doppler ultrasonic angiography were examined. Among them,
      1527 had remote cerebral stroke and 285 had carotid endarterectomy. The results
      indicated that the group of carotid endarterectomy conformed to Doppler
      ultresonic angiograph of preoperation and were consistent with 10 positive and 10
      negative cases of random sampling. The method has advantages of easy operation,
      time-saving, low expenses, no complication and reliable diagnosis to use Doppler
      ultrasonic angiograph in carotid surgery. It was worth spreading in non-invasive
      arterial morphology and hemodynamics.

PMID- 9590791
TI  - [SMC proliferation and its distribution in autologous vein grafts].
AB  - SMC proliferation in intimal hyperplasia is a major cause of graft failure. We
      induced experimental jugular vein to aortic autograft in 120 Wistar rats, and
      analyzed the SMC proliferation and its distribution in the graft by flow
      cytometry (FCM) and immunohistochemistry of proliferating cellular nuclear
      antigen (PCNA) from 2 hours, 6 hours, 24 hours to 1 week, 2 weeks and 4 weeks.
      Although the number was not apparently increased in autologous vein graft at
      early stage, SMC proliferation had started. At 1 week after transplantation, the
      activity of SMC proliferation increased to a maximum, and returned to baseline
      level 4 weeks. At early stage, the distribution of SMC proliferation located in
      the media, but at middle stage, both intima and media all presented a relatively
      higher proliferative activity. The intima formation occurred by the migration of
      a large population and the proliferation of a relatively small subpopulation of
      SMC. Therefore, control of SMC proliferation, and migration of autologous vein
      grafts must be within two weeks after transplantation.

PMID- 9590792
TI  - [Gene therapy of peripheral vascular diseases].

PMID- 9590794
TI  - [Clinical application of spleno-renal shunt].
AB  - The results of splenorenal shunt (SRS) in 405 patients were compared with those
      of simple splenectomy (SS) in 376 cirrhotic patients in the treatment of portal
      hypertension. The recurrent bleeding rate was 10.12% in SRS group and 21.2% in SS
      group, respectively (P < 0.001). The mortality of rebleeding was 2.96% in SRS
      group and 10.6% in SS group, respectively (P < 0.01). Death from hepatic failure
      developed at 16.5% of SRS patients and at 9.8% of SS patients, respectively (P <
      0.01). The rate of postoperative variceal bleeding and mortality in prophylactic
      SRS group were 4.9% and 6.2%, and 15.1% and 26.4% in prophylactic SS group,
      respectively (P < 0.01). The authors are in favor of prophylactic SRS and
      modified side-to-side SRS for its simplicity and good results.

PMID- 9590793
TI  - [Effects of preoperative transcatheter hepatic arterial chemoembolization (TAE)
      on the prognosis of patients with hepatic carcinoma undergoing tumor resection].
AB  - This study consists of 77 hepatocellular carcinoma patients. Twenty-six (Group A)
      received preoperative TAE and 51 did not (Group B). Group A and B were further
      divided into two subgroups according to their tumor size i.e. Group A1 and B1
      (tumor size 3-8 cm); Group A2 and B2 (tumor size > 8 cm). The 1-, 2-, 3-year
      disease free survival rates were 50.0%, 33.3%, 16.6% for Group A1 and 72.7%,
      54.2%, 39.7% for Group B1; 75.0%, 56.2%, 45.0% for Group A2 and 38.9%, 32.4%,
      10.8% for Group B2 respectively. The 1-, 3-, 5-years survival rates were 85.7%,
      31.2%, 0 for Group A1 and 84.8%, 58.7%, 27.9% for Group B1; 91.6%, 82.5%, 53.0%
      for Group A2 and 77.8%, 30.1%, 0 for Group B2 respectively. There were
      significant differences between Group A2 and B2 both in disease free survival
      rate and 5-year survival rate (P < 0.05). The results also demonstrated that the
      preoperative TAE did worsen the prognosis of patients with tumor size between 3-8
      cm (Group A1) with disease free survival rate and 5-year survival rate shorter
      than that of Group A2.

PMID- 9590795
TI  - [Experience of laparoscopic vagotomy for the treatment of chronic duodenal
      ulcer].
AB  - Ten patients with chronic duodenal ulcer underwent posterior truncal vagotomy
      combined with anterior seromyotomy of lesser curvature of the stomach (Taylor's
      procedure). Perioperative acid secretory studies (Horlland test) and gastric
      emptying tests were performed. Postoperative recovery was uneventful in all
      patients. The acid secretory studies showed decreased BAO, MAO and PAO (P <
      0.01). The postoperative gastric emptying was significantly delayed, and the
      patients are all symptom free. Follow up gastroscopy revealed ulcer healing in 7
      patients.

PMID- 9590796
TI  - [Hashimoto's disease with thyroid cancer: report of six cases].
AB  - Hashimoto's disease associated with thyroid cancer is not common. From January
      1976 to December 1994, a total of 95 patients with Hashimoto's disease were
      treated surgically. Six (5 Papillary 1 folicular) of 95 patients had thyroid
      cancer which was concomitantly revealed pathologically. They were all women with
      mean age of 30.3 years. The size of tumor was 0.3-2.0 cm. Follow-up for 1-17
      years showed that they were all alive and healthy. Two patients were misdiagnosed
      as having anaplastic carcinoma but the definitive diagnosis by
      immunohistochemical analysis was thyroid malignant lymphoma (B-cell type).
      Hashimoto's disease and thyroid cancer relationship, diagnosis, and treatment are
      discussed.

PMID- 9590797
TI  - [Percutaneous transluminal angioplasty in the treatment of 79 cases of reno
      vascular hypertension].
AB  - 79 cases of reno-vascular hypertension were treated with percutaneous
      transluminal angioplasty (PTRA) during 1981-1994. Athrosclerosis as the etiology
      of renal artery lesions was noted in 14 cases (17.7%), arteritis in 57 (72.2%),
      and fibro-muscular dysplasia in 8 (10.1%). The success rate of PTRA was 94.8%.
      The morbidity rate was 3.8%. There was no mortality in this series. The cure
      improvement rate after average follow-up of 44.8 months was 73.4%. It was 75.4%
      in the group of arteritis. We conclude that PTRA should be considered as the
      first choice for the treatment of renovascular hypertension, especially to the
      arteritis patients.

PMID- 9590798
TI  - [The relationship between prognosis of esophageal squamous carcinoma and
      Langerhans cell].
AB  - The operative tumor specimen of esophageal squamous carcinoma were studied with
      immunohistochemical (ABC) method S-100 protein staining. Under the light
      microscopy, we observed the morphology, number and distribution of Langerhan's
      cells (LC) in different portion of the tumor mass and its relationship with the
      pathological staging in 167 cases. We observed also the relationship between LC
      and the postoperative survival period in 127 cases followed for more than 3
      years. These results suggested found that positive relation between the number of
      LC in the cancer nest and in the lymphfollicle with the increasing of TNM
      classification. The number of LC in the cancer nest significantly increased in
      state III and IV cases than II cases. On the contrary, the number of LC in the
      peritumor and interstitial tissue decreased while the TNM classification was
      increasing. These findings suggested that the survival period was shorter in
      patients whose LC had increased in the cancer nest, whereas the survival period
      would be longer in those patients whose LC had increased in the tissue around the
      tumor mass, in the mucosa near the tumor as well as in the interstitial tissue.
      These two points might be used as an immunological para-meter for the assessment
      of the prognosis.

PMID- 9590799
TI  - [Valve replacement in children].
AB  - We report 27 children aged 2-14 years underwent valve replacement. Twelve
      patients underwent mitral valve replacement, 11 tricuspid valve replacement, and
      4 aortic valve replacement. Of them, 16(59.3%) were associated with cardiac
      malformation, 23 were in NYHA functional class III and IV in preoperation. 13
      patients required additional procedures. There were 3 hospital deaths (11.1%), 4
      late deaths (16.6%), and 2 reoperation. Our experiment suggested that the greater
      type of mechanical valve be essential for valve replacement in children, but
      suture technique be modified for the children with small valvular ring. After
      replacement of mechanical valve, low concentration anticoagulation therapy is
      considered as a safe and reliable method.

PMID- 9590800
TI  - [Mannital induced acute renal failure].
AB  - 14 cases of mannitol-induced acute renal failure were reported. The dosage of
      mannitol used varied widely. In all cases serum Na+, HCO3- were decreased, K+ and
      BUN increased significantly. Serum osmolality was measured in 5 cases. The
      osmolal gap was increased greatly, 77.4mOsm/kg. H2O in average. The increase of
      osmolal gap may play an important role in acute renal failure by causing
      intensive renal vasocontraction. Monitoring of serum osmolality or osmolal gap
      can help to prevent mannitol intoxication. The decrease of serum Na+ may be a
      warning sign of increased osmolal gap. Hemodialysis is the best way for the
      treatment of mannitol-induced acute renal failure.

PMID- 9590801
TI  - [Treatment of recurrent anterior dislocation of the shoulder with pectoralis
      minor muscle-bone flap].
AB  - We treated 10 patients with recurrent anterior dislocation of the shoulder by
      transplantation of pectoralis minor muscle-bone flap transplanted to the upper
      part of the humerus. All patients were followed-up for an average 31 months and
      no recurrent was found. We consider that the muscle beily exerts a protective
      effect like a barrier on the weak anterio inferior region of the shoulder and
      increases the force for extending the shoulder and lifting the arm. The operation
      is based on biomechanics. Meanwhile, suturing the laxative joint capsule and
      repairing the weak anteroinfeior region of the shoulder is more beneficial to
      prevent from redislocation of the humerus head.

PMID- 9590802
TI  - [A comparison of the modified gamma nail and the ender nail for treatment of
      intertrochanteric fractures].
AB  - We made a comparison between the modified Gamma nailing and the Ender nailing in
      the treatment of 102 patients with intertrochanteric fracture. Sixty patients
      were treated with the modified Gamma nailing and forty-two patients with the
      Ender method. The preoperative conditions of the patients in the two groups were
      similar as showed by statistical analysis. More intraoperative bleeding was
      recorded in the modified Gamma nail group. However, there were a earlier full
      weight -bearing, a better hip function and a lower rate of operative complication
      in the patients treated with the modified Gamma nailing. We conclude that with
      the modified technique and the modified femoral component the Gamma nail is
      advanced in the treatment of intertrochanteric fracture. However, it is danger to
      apply in elderly patients accompanied with certain vital problems. For these
      patients the Ender nail may be considered.

PMID- 9590803
TI  - [Effect of escharectomy during burn shock stage on bacterial and endotoxic
      translocation from the gut].
AB  - 120 SPF rats (Wistar) were randomly divided into 3 groups (1) simple skin
      grafting group (Group A). (2) Escharectomy during burn shock group (Group B). (3)
      Routine escharectomy group (Group C) Full-thickness burn of 30% TBSA was produced
      in Group B and Group C. One hour after scald intravenous fluid replacement was
      instituted. First stage escharectomy has been performed 24 hours after burn and 5
      days postburn. The results demonstrated that the contents of both plasma LPS and
      TNF in Group B were significantly lower as compared with these in Group C. Our
      data indicated escharectomy during burn shock would effectively eliminate the
      effects of the endotoxemia. Endotoxin play an important role in the bacterial and
      endotoxic translocation.

PMID- 9590804
TI  - [Status and role of ophthalmic pathology in ophthalmology].

PMID- 9590805
TI  - A molecular pathologic study on apoptosis in retinoblastoma and the mechanism of
      spontaneous regression in retinoblastoma.
AB  - OBJECTIVE: The present study was designed to prove the existence of apoptosis in
      retinoblastoma (Rb) and to determine the pathogenic mechanism of spontaneous
      regression of Rb as well as the relationship between them. METHODS: Qualitative
      morphological study on Rb was performed by means of light microscope, electron
      microscope and TdT mediated biotin-dUTP nick-end labeling (TUNEL). Quantitative
      study was performed by automatic image analysis technology (AIAT) stained with
      Feulgen reaction. RESULTS: The characteristic regressed area occurred in all 47
      cases of Rb. Morphological changes observed within Rb closely resembled the
      apoptotic cell described by Kerr et al in 1972. Under electron microscope,
      details of apoptosis were observed in 7 cases of Rb: the morphological sequence
      of events occurred in and around the cell nucleus. The morphology of the TUNEL
      labeling Rb cell was various. TUNEL labeling showed more positive cells in
      regressed area, while fewer in advanced area. AIAT revealed that apoptosis index
      (AI) in regressed areas was higher than that in other areas of Rb, DNA average
      ploidy (DP) consisted with the histology grade of Rb, the degree of hyperdiploid
      (DH) in metastatic area was distinctly higher than that in other areas (P <
      0.05). CONCLUSIONS 1. Morphologic evidence proved the existence of apoptosis,
      especially more in regressed area of Rb. 2. Apoptosis may participate in the
      spontaneous regression of Rb. Apoptosis contributed to the spontaneous regression
      of Rb. 3. Tumor growth parameters of Rb (AI, DP, DH) obtained by AIAT may be used
      as quantitative index for pathologic classification, the selection of clinical
      treatment and the prognostic evaluation.

PMID- 9590806
TI  - [Observation of the invasion of retinoblastoma cells to the corneal epithelial
      cells and keratocytes in culture].
AB  - OBJECTIVE: To study the invasive ability of retinoblastoma cells into the corneal
      epithelial cells and keratocytes in culture. METHODS: SO-Rb50 cells of
      retinoblastoma, corneal epithelial cells and keratocytes were co-cultured. The
      morphological changes of SO-Rb50 cells adherent to the corneal epithelial cells
      and keratocytes were observed. The distribution of proteoglycans in the SO-Rb50
      cells, corneal cells and keratocytes was analyzed by histochemical method and
      electron microscopy. RESULTS: SO-Rb50 cells could adhere to the keratocytes, but
      did not adhere to the corneal epithelial cells. There are common hyaluronidase
      resistant and chondroitinase-resistant proteoglycans on the surface of SO-Rb50
      cells and corneal epithelial cells. Chondroitin is present on the surface of
      keratocytes. CONCLUSION: It is considered that the cell surface proteoglycans may
      play an important role in mediating SO-Rb50 tumor cell adhesion and non-adhesion
      to normal cells.

PMID- 9590807
TI  - [An experimental study of pathomorphology in the iris and ciliary body after
      intraocular lens implantation].
AB  - OBJECTIVE: To study the pathological changes and morphological features in the
      iris and ciliary body after lens extraction and intraocular lens (IOL)
      implantation in rabbits and discuss the mechanism of postoperative intraocular
      inflammatory response. METHODS: 27 adult pigmented rabbits were divided into
      three groups, (1) extracapsular lens extraction and IOL implantation. (2) simple
      extracapsular lens extraction, and (3) the control group without surgical
      intervention. The iris and ciliary body in every eye were taken on the 1st, 7th
      and 14th days after surgery, their pathological changes were observed with light
      microscopy, and the number of inflammatory cells were counted. The data were
      analyzed by using analysis of variance of SAS software. RESULTS: The pathological
      changes might be divided into three stages: (1) acute inflammation and exudative
      changes in the early stage (on the 1st day postoperatively), (2) subacute
      inflammation and granuloma formation in the middle stage (on the 7th day
      postoperatively, and (3) chronic inflammation and fibrosis in the late stage (on
      the 14th day postoperatively). CONCLUSION: The inflammatory cells in the iris and
      ciliary body are significantly higher in eyes with IOL implantation than that in
      eyes with simple extracapsular lens extraction (P < 0.01). Besides macrophages,
      there are many lymphocytes, eosinophils and plasma cells in the iris and ciliary
      body, suggesting that an active immune response exist in the inflammation.

PMID- 9590808
TI  - [Quantitative analyses of DNA content and P53 gene product expression from
      epithelial lacrimal gland tumors].
AB  - OBJECTIVE: To investigate the significance of quantitative analyses of DNA
      content and P53 gene product expression which are applied for pathological
      diagnosis of epithelial lacrimal gland tumor. METHODS: Flow cytometry (FCM) and
      immunofluorescence staining technique were used to quantitatively measure the DNA
      content and expression of P53 gene product from 39 cases with epithelial lacrimal
      gland tumors. RESULTS: It is indicated that the pleomorphic adenomas still
      possess of the properties of DNA diploid of normal lacrimal gland cell, but
      malignant tumors are characterized by DNA aneuploidy. There is a significant
      difference in the content of expression of P53 gene product between pleomorphic
      adenomas and malignant tumors (P < 0.001). The content of expression of P53 gene
      product is positively correlated to the DNA content, and both are increasing with
      the reduction of tumor tissue differentiation. CONCLUSION: Quantitative analyses
      of DNA content and expression of P53 gene product may provide objective indexes
      for the pathological diagnosis of epithelial lacrimal gland tumor.

PMID- 9590809
TI  - [Automatic image analysis of argentophil protein granule quantitative measurement
      on nucleolus area of limbus epithelial neoplasms].
AB  - OBJECTIVE: To study the pathological diagnostic significance of argentophil
      protein (AgNOR) quantitative analysis at nucleolus area of limbus epithelial
      neoplasms. METHODS: Automatic image analysis system was used for argentophil
      protein granule measurement in the pathologic diagnosis of 45 cases with limbus
      epithelial neoplasms, including benign hyperplasia, atypical hyperplasia,
      carcinoma in situ and squamous cell carcinoma. RESULTS: In various lesions, there
      were the differences in the distributive pattern, size and area of AgNOR
      granules, which were closely related to the nature of the neoplasms (benign or
      malignant) and its cell differentiation. CONCLUSION: Automatic image analysis of
      AgNOR quantitative measurement on limbus epithelial neoplasms may indicate the
      proliferative activity and cell differentiation in various lesions, help to
      differentiate benign or malignant neoplasms and effectively enhance the level of
      pathologic diagnosis.

PMID- 9590810
TI  - [A study of 5-fluorouracil on bovine trabecular meshwork cells in vitro].
AB  - OBJECTIVE: To determine whether the clinical use of 5-fluorouracil (5-FU) may
      have any toxic effects on trabecular meshwork cells. METHODS: Bovine trabecular
      meshwork (BTM) cells were cultured in vitro. The effects of 5-FU on BTM cells
      concerning cellular morphology, ultrastructure, vitality and phagocytosis were
      observed. RESULT: The safe dosage of 5-FU on BTM cell was 1 x 10-6g.ml-1.
      CONCLUSION: Based on the pharmacokinetic data in the rabbit anterior chamber, it
      is suggested that the 5-FU dosage of conventional use cause no injury to human
      trabecular meshwork cells.

PMID- 9590811
TI  - [Histopathological classification of 3,510 cases with eyelid tumor].
AB  - OBJECTIVE: To study the histopathological classification of eyelid tumor. METHOD:
      The pathological specimens of 3,510 cases with eyelid tumor examined between 1953
      1992 were retrospectively analyzed. RESULTS The 5 leading malignant lid tumors
      were basal cell carcinomas (430 cases, 37.6%), meibomian gland carcinomas (363,
      31.7%), squamous cell carcinomas (216 cases, 18.9%), melanomas (56 cases, 4.9%)
      and malignant lymphomas (21 cases, 1.8%). The 5 leading benign lid tumors
      including papillomas (658 cases, 27.9%), pigmented nevi (578 cases, 24.4%), cysts
      (427 cases, 18.1%), angiomas (222 cases, 9.4% including 10 lymphangiomas) and
      verrucae (212 cases, 9.0%). Rare tumors of the eyelid included one case of each
      of the following tumors: reticulum cell sarcoma, adenocystic carcinoma, malignant
      mesenchymoma, mucinous adenocarcinoma, Bowen's disease, basosquamous carcinoma,
      basosebacious carcinoma, teratoma, granular cell tumor (myoblastoma),
      angiolymphoid hyperplasia with eosinophilia, osteoma, etc. CONCLUSION: The
      classification and differentiation in type of eyelid tumor are beneficial to the
      histopathological diagnosis.

PMID- 9590812
TI  - [An ultrastructural pathological study of pterygium].
AB  - OBJECTIVE: To study the ultrastructural changes of pterygium. METHOD: The
      pathological ultrastructure of pterygium was studied by Hu-12A transmission
      electron microscopy in 14 specimens. RESULTS: The result indicated that normal
      and abnormal elastic fibers and collagenous fibers existed in the pterygium. As
      hyperplastic fibers intruded into the corneal subepithelium, Bowman's membrane
      was broken. To a certain extent, blood vessel multiplication and degeneration
      were found in the pterygium. One of the important factors was blood vessel
      multiplication and degeneration which affected the occurrence and development of
      pterygium. CONCLUSION: Multiplication and degeneration of elastic and collagenous
      fibers were the prominent pathological changes, and the pre-elastic fibers and
      denatured elastic fibers were the main compositions of pterygium.

PMID- 9590813
TI  - [The characteristics of macular branch retinal vein occlusion].
AB  - OBJECTIVE: The study was designed for the analysis on data of 51 patients with
      macular branch retinal vein occlusion (McBRVO) and the comparison between them
      and 210 patients (214 eyes) with major branch retinal vein occlusion (MjBRVO).
      METHODS: Fluorescein angiography, ophthalmoscope and slit-lamp were used for the
      examination of the venous obstructive site and the locations of artery and vein.
      RESULTS: (1) The incidence of McBRVO was 19.5% (51/261) in branch retinal vein
      occlusion. (2) The site of occlusion: the incidence of McBRVO at supero-temporal
      branches was 72.5% (37/51) and the incidence of MjBRVO was 73.4% (157/214). (3)
      The involved branch at the first macular branch accounted for 39.6%, the second
      branch 58.3%, and the third branch 2.1%. The artery anterior to the vein at
      arteriovenous crossing at the obstructive site accounted for 93.0% in the McBRVO
      group and 95.0% in the MjBRVO group. (4) The complications and visual prognosis:
      The incidence of cystoid macular edema was 20.0% in McBRVO group and that was
      28.5% in the MjBRVO group. No neovascularization was found in the McBRVO group,
      while 37.9% neovascular formation was found in the MjBRVO group. The visual
      acuity recovered to 0.5 or better was in 88.2% in the McBRVO group, while 57.0%
      in the MjBRVO group (P < 0.005). CONCLUSION: There are no significant differences
      in sex, age, laterality, pathogenesis as well as occlusion site between the
      McBRVO and MjBRVO groups, but the visual prognosis is better in the former than
      that in the latter group.

PMID- 9590814
TI  - [Treatment of central retinal artery occlusion with thrombolysis via
      superselective ophthalmic artery catheterization].
AB  - OBJECTIVE: To investigate the therapeutic effect of thrombolysis via
      superselective ophthalmic artery catheterization for treatment of central retinal
      artery occlusion (CRAO). METHOD: Urokinase was directly infused via ophthalmic
      artery (OA) or common carotid artery by catheterization after angiography into 4
      eyes of 4 patients with CRAO, The times of onset ranging from 7 to 14 days.
      RESULTS: The visual acuity was significantly improved in 2 eyes. No visual change
      was found in 2 eyes in which the beginning part of internal carotid artery (ICA)
      or OA was occluded. There was no complications. CONCLUSIONS: Good results were
      obtained in the eyes in which thrombolysis was launched early in the course of
      the disease and urokinase was successfully infused into the OA. It seems that
      there is no effect for the eyes complicated with occlusion in ICA and OA.

PMID- 9590815
TI  - [Evaluation for therapeutic efficacy of decompression of optic nerve canal in 121
      cases].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of decompression of optic nerve
      canal in the eye with indirect nerve injury in the optic nerve canal. METHODS:
      121 patients with indirect injury of optic nerve in the canal were selected and
      decompression of optic nerve canal was performed on them. Then the outcomes were
      reviewed and analyzed. RESULTS: Visual acuities of 76 patients (62.81%) were
      improved. CONCLUSION: It is obvious that decompression of optic nerve canal is
      associated with significant improvement in cases with good preoperative vision.
      In cases without light perception, treatment of steroids and dehydrant should be
      firstly applied, afterwards according to the patient's individual situation,
      selectively the case is to perform the operation. Thus the therapeutic
      effectiveness can be greatly elevated. Decompression of optic nerve canal is safe
      and reliable.

PMID- 9590816
TI  - [Exploratory vitrectomy for traumatized eyes with no light perception and dense
      vitreous hemorrhage].
AB  - OBJECTIVE: To evaluate the efficacy of exploratory vitrectomy for certain
      traumatized eyes with no light perception (NLP) and dense vitreous hemorrhage.
      METHOD: We performed vitrectomy on 10 patients with NLP eyes after ocular trauma.
      Of them, eight had open globe injuries and two had closed blunt ocular trauma.
      RESULTS: Postoperatively, six had visual acuities of light perception to 0.25 and
      four remained NLP. In most eyes, a potentially functional posterior retina and
      optic disc were observed during surgery. CONCLUSION: Dense vitreous hemorrhage
      could be the most important factor for NLP after severe ocular trauma. Therefore,
      NLP does not always mean permanent loss of vision. Proper primary repair of the
      wound and timely vitrectomy may give a chance of visual recovery in selected
      traumatized eyes.

PMID- 9590817
TI  - [A study on lens epithelial cell DNA damage induced by hydrogen peroxide in rat
      and its repair].
AB  - OBJECTIVE: The induction and repair of DNA single-strand breaks (SSBs) were
      measured in primary cultured infant rat lens epithelial cells (RLECs) following
      hydrogen peroxide (HP) exposure, and the influential factors were detected.
      METHODS: Utilizing nick translation methodology which utilizes incorporation of
      labeled nucleotides at the sites of DNA SSBs to sensitively quantitate the
      damage, we studied the effects of temperature, doses of HP and trace amount of
      selenium on cell survival. RESULTS: The number of DNA SSBs at 37 degrees was
      higher than that at 4C (P < 0.01). Significant numbers of SSBs were detected
      after being insulted by as low as 36.4 mumol/L hydrogen peroxide for 12 minutes 4
      degrees (P < 0.05). Repair rapidly initiated and almost completed in 60 minutes
      after mild damage, and it was unable to repair when the DNA damage was induced by
      HP at toxic concentration. Trace selenium was added to the culture and incubated
      for 24 hours, then the number of SSBs was significantly decreased (P < 0.01).
      CONCLUSIONS: At 37 degrees HP may induce DNA SSBs in RLECs. HP induces the SSBs
      in a dose dependent manner. The DNA SSBs can not be repaired after severe damage.
      Trace selenium can decrease the degree of susceptibility to oxidative damage in
      infant RLECs.

PMID- 9590818
TI  - [An experimental study on immune mechanism after alkali burn in the anterior
      segment of rabbit eye].
AB  - OBJECTIVE: To study the immunologic mechanism of corneal ulceration after alkali
      burn. METHODS: 55 rabbits with alkali burn in right eye were randomly divided
      into two groups. In group I (31 animals), the level of circulating immune complex
      (CIC), the rate of red blood cell C3b receptor complex rosette (RBC-C3bRR) and
      immune complex rosette (RBC-ICR) were measured respectively at 7, 14, 21, 35, 49
      days after alkali burn. In Group 2 (24 animals), the immune complex was detected
      by means of immunofluorescence (IF) and immunogold-silver staining (IGSS) in
      burned tissues at 21 days after burn. Histopathologic changes were also observed
      under light microscope. RESULTS: CIC, the rate of RBC-C3bRR and RBC-ICR were
      markedly increased 14 to 21 days after burn. In the mean time, the deposition of
      immune complex was found in burned tissues and the accumulation of
      polymorphonuclear leukocyte (PMN) was observed at the base of corneal ulcer.
      CONCLUSIONS: The immune mechanism indeed participates in the pathogenesis of
      corneal ulceration and also aggravates the progress of ulceration on the base of
      chemical injury.

PMID- 9590819
TI  - [Rapid development of cataract surgery and intraocular lens implantation in
      China].

PMID- 9590820
TI  - Cataract extraction by phacoemulsification in situ and elliptical intraocular
      lens implantation.
AB  - OBJECTIVE: To investigate the technique of phacoemulsification in situ for
      cataract extraction and elliptical intraocular lens (IOL) implantation. METHODS:
      60 eyes of 57 cases with cataract were included and the hardness of nucleus was
      grade-1-2 in 25 eyes, grade-3 in 27 eyes and grade-4 in 8 eyes. Tunnel incision
      was made and in situ phacoemulsification with elliptical (5 mm x 6 mm) IOL
      implantation was performed on all the cases. RESULTS: Phaco-spent-time was 45
      seconds to 3 minutes 45 seconds (average 1 minute 52 seconds).
      Phacoemulsification in 53 eyes (88.3%) was successful in situ Visual acuities of
      0.5 or better and 1.0 or better at postoperative one week were obtained in 75.0%
      and 56.7%, and at 1-12 month follow-up in 85.0% and 71.7% respectively.
      CONCLUSION: The technique of phacoemulsification in situ and elliptical IOL
      implantation is worthy to be spread due to minimum postoperative astigmatism and
      fast restoration of visual acuity.

PMID- 9590821
TI  - [Extra-capsular cataract extraction and intraocular lens implantation in cases
      with cataract and a small pupil with synechiae].
AB  - OBJECTIVE: To introduce a new surgical technique for cataract with a small
      synechia pupil and evaluate its effects. METHODS: 43 eyes of 40 patients were
      operated on and followed up for 3-30 months. Surgical procedures included
      iridectomy, separating the posterior synechiae, straight cutting of upper iris
      and making 3 little cuts at inferior pupillary margin, extracapsular cataract
      extraction, intraocular lens implantation, and at last suturing the iris cuts to
      form a round pupil. RESULTS: Postoperatively, all 43 eyes had 3-4 mm basically
      round pupil and 42 eyes (97.7%) had improved vision. Of the 32 eyes followed up
      for more than three months, 22 eyes (68.8%) obtained visual acuities 0.5 or
      better, 10 eyes (31.2%) had visual acuities worse than 0.4 which were attributed
      to posterior segment abnormalities. Intraoperatively, no posterior capsular
      rupture was seen, and postoperatively, no severe complications were found.
      CONCLUSION: The results suggest that patients with cataract and a small synechia
      pupil obtain improved vision and round pupil without unacceptable risk by means
      of the surgical technique mentioned in this paper.

PMID- 9590822
TI  - [A study of suitable age for intraocular lens implantation in children according
      to ocular anatomy and development].
AB  - OBJECTIVE: To study the suitable age for intraocular lens (IOL) implantation in
      children. METHODS: 240 (240 eyes) normal children aged 3-13 years old were
      selected. Their corneal refraction, anterior chamber depth, lens thickness and
      ocular axial length were measured with Roden-Stock Keratometer C-MES and Eyescan
      Model 55 separately. RESULTS: The corneal refraction of 3-year-old children, the
      anterior chamber depth and lens thickness after 5 years old, and the ocular axial
      length after 9 years old approach the adult magnitude. CONCLUSIONS: A 3-year-old
      child has been qualified with IOL implantation, the child younger than 9 years
      old should be implanted with a normal adult IOL and then corrected with glasses,
      and a child after 10 years old should be directly implanted with a proper
      dioptric IOL.

PMID- 9590823
TI  - [Inhibition of rabbit lens epithelial cell proliferation].
AB  - OBJECTIVE: To study the ability of homoharringtonine, 5-fluorouracil and
      adriamycin on inhibiting the proliferation of rabbit lens epithelial cells (RLEC)
      and the prevention of after cataract by using homoharringtonine. METHODS: RLEC
      were isolated and cultured. (1) The passage RLEC were placed in 24-well tissue
      culture plates and incubated for 48 hours, then exposed to different
      concentrations of homoharringtonine, 5-fluorouracil and adriamycin for 24 and 72
      hours; (2) The passage RLEC and homoharringtonine, 5-fluorouracil, adriamycin
      were placed and cultured for 24 hours to investigate the rate of attached cells;
      (3) The morphological changes of RLEC were studied under light microscope.
      RESULTS: The ID50 of homoharringtonine, 5-fluorouracil and adriamycin exposed to
      RLEC for 24 hours were 0.84 micrograms, 0.58 micrograms and 4.50 ng/ml and those
      for 72 hours were 0.49 micrograms, 0.33 micrograms and 3.85 ng/ml respectively.
      In the homoharringtonine group, the rate of attached cells was less than that of
      5-fluorouracil and adriamycin groups. The study of the morphological changes
      showed that the different concentrations of antiproliferative drugs affected on
      RLEC at different regions. CONCLUSION: The authors consider that
      homoharringtonine may be more effective for the prevention of after cataract than
      5-fluorouracil and adriamycin.

PMID- 9590824
TI  - [An experimental study of cytology in the aqueous humor of rabbit eyes after
      intraocular lens implantation].
AB  - OBJECTIVE: The study was designed to count the number of white blood cells and
      observe their subset distribution in the aqueous humor after extracapsular lens
      extraction and intraocular lens (IOL) implantation in capsular bag in rabbits and
      to discuss the mechanism of postoperative intraocular inflammatory response.
      METHODS: 27 adult pigmented rabbits were divided into three groups: (1) The IOL
      was placed in the capsular bag after extracapsular lens extraction; (2) The
      extracapsular lens extraction; and (3) The control group without any surgical
      intervention. Aqueous humor samples were aspirated on the postoperative 1, 3, 7
      and 14 days, and the total number of white blood cells in the aqueous humor and
      their subset distribution were counted. The data were analyzed by using analysis
      of variance of SAS software. RESULTS: There was a significantly higher number of
      inflammatory cells in the IOL implanted eyes than that in the eyes with only
      extracapsular lens extraction. CONCLUSIONS: In the early postoperative stage,
      there was a marked increase in the number of white blood cells and
      polymorphonuclear leukocytes in the IOL group, that is probably related to the
      mechanical ocular tissue damage and the breakdown of the blood-aqueous barrier
      induced by the operative procedures. There were a significant increase in the
      macrophages, eosinophiles, and lymphocytes in the IOL group, that suggests that
      an active immune response exist in the anterior ocular inflammation after IOL
      implantation.

PMID- 9590825
TI  - [Topographic stereoscopic measurements of optic disc in early primary open angle
      glaucoma].
AB  - OBJECTIVE: To search a sensitive parameter for the early diagnosis of primary
      open angle glaucoma (POAG). METHOD: A system of computerized image analysis was
      used to acquire images of the optic nerve head of patients with POAG, suspect
      glaucoma (SG) and of normal persons. Each of these groups contained 31 eyes of 31
      cases. The mean relative depths of disc rim and cup at different areas in the
      optic nerve head were measured. All these patients were followed up for four to
      six months, and the changes of the mean depths of every sector were compared
      between each pair of the three groups with statistic analysis. RESULTS: The mean
      depth of the neural rim and cup of each sector and that of total rim and total
      cup of POAG and SG patients were all deeper than that of normal controls. The
      mean depths of neural rim of the superior sector, inferior sector and the total
      rim area of POAG were deeper than that of SG patients. Compared to their first
      measurements, the changes of mean depths of neural rim of superior sector and
      total neural rim area of POAG patients were more prominent than that of normal
      controls and SG. We also compared the relative depth of the total rim area in the
      different areas in the optic nerve head with other two dimensional optic disc
      parameters such as cup/disc ratio, etc. CONCLUSION: Our study suggests that three
      dimensional stereoscopic measurement of the surface of optic nerve head and
      follow-up be of paramount importance in the early diagnosis of POAG patients.

PMID- 9590826
TI  - [Determination of color pattern visual evoked potential in early primary open
      angle glaucoma].
AB  - OBJECTIVE: To evaluate the clinical significance of changes of color visual
      evoked potential (PVEP) in early primary open angle glaucoma (POAG). METHOD:
      Thirty-one patients (45 eyes) with POAG and fifty-one persons (94 eyes) as age
      matched normal controls were tested by color PVEP. RESULTS: In POAG group, the
      latencies of P100 wave were lengthened, its amplitudes and wave form indexes
      decreased, the latencies of N145 wave were lengthened, and the amplitudes of N75
      wave were lowered. In early POAG eyes without the changes detected by Goldmann
      perimetry, their color PVEPs were already abnormal. Stepwise regression analysis
      shows that four factors in color PVEP are correlated to the defect of visual
      field in POAG. It is proved with the stepwise discriminatory analysis that seven
      factors in the color PVEP are useful in the diagnosis of early POAG. CONCLUSIONS:
      Several factors in color PVEP are abnormal in POAG. In early POAG eyes without
      changes detected by Goldmann perimetry, their color PVEPs are already abnormal.
      By using discriminatory function, the positive rate of the diagnosis of early
      POAG tested by color PVEP might be increased.

PMID- 9590828
TI  - [The clinical application of liquid perfluorocarbon in ophthalmology].
AB  - OBJECTIVE: To evaluate the clinical value of liquid perfluorocarbon (LPFC)
      application in ophthalmology. METHODS: From June to December in 1994, six cases
      of retinal detachment with giant retinal tear larger than 270 degrees were
      treated, and LPFC was used in all the cases. The physicochemical properties of
      LPFC, the surgical method, surgical indication and complications were discussed.
      RESULTS: The retina in all cases was reattached and their vision improved.
      CONCLUSION: LPFC is valuable in treatment of retinal detachment.

PMID- 9590827
TI  - [Corneal astigmatism following trabeculectomy].
AB  - OBJECTIVE: The study was designed to investigate the change of corneal
      astigmatism following trabeculectomy. METHODS: Before and after the operation at
      different periods, the corneal astigmatism of 42 eyes was evaluated by Topcon-OM
      3 keratometer. RESULTS: Almost the corneal astigmatism of all the cases was with
      the-rule in the early stage after trabeculectomy. Among them, the astigmatism in
      41.03% of cases was more than 2.00D, 3 months post-operatively 17.50% shifted
      towards against-the-rule, and 9.50% remained more than 2.00D which was induced by
      the surgery. CONCLUSION: Trabeculectomy may cause certain with-the-rule corneal
      astigmatism. The corneal astigmatism in most of the cases may decrease as time
      passes by.

PMID- 9590829
TI  - [The study on changes of macular light sensitivity before and after
      photocoagulation for diabetic macular edema].
AB  - OBJECTIVE: The study was designed to determine whether laser photocoagulation
      could damage macular visual function in treatment of diabetic macular edema.
      METHODS: A prospective clinical trial was taken to determine the effects of argon
      green (514.5nm) laser photocoagulation on macular light sensitivity (MLS) by
      comparing the self MLS pairing data collected from a Humphrey automatic visual
      field analyzer before and after the procedure. Nineteen eyes of 15 patients with
      diabetic macular edema consistent with its diagnostic criteria were enrolled in
      this study, a follow-up period being 3 months. RESULTS: The mean MLS at the
      photocoagulation area, non-photocoagulation area, 5 degrees and 13 degrees
      eccentricity were significantly decreased within 1 week after the treatment, the
      drops of MLS were 1.85 dB, 1.05 dB, 0.99 dB, 1.66 dB respectively (P < 0.05). The
      mean reduction of MLS at the fovea within 1 week after the treatment has no
      statistical significance. The MLS gradually recovered at the 1st and 3rd month
      after photocoagulation, and the visual acuities in most of the cases were stable
      or increased. CONCLUSIONS: MLS is affected little by laser photocoagulation, and
      photocoagulation can reduce the risk of visual loss or increase visual acuity in
      an eye with diabetic macular edema.

PMID- 9590830
TI  - [Diagnostic significance of CT in the orbital inflammatory lesions].
AB  - OBJECTIVE: To analyze and summarize the CT signs of orbital inflammatory lesions.
      METHOD: HITACH-W, or EXEL 2400 pattern of CT was applied for the orbital scanning
      of 52 cases with orbital inflammatory lesions proved by clinicopathology.
      RESULTS: The CT signs of orbital inflammatory lesions in our series included
      exophthalmos, orbital mass, ill-marginated mass, multiple space involvement,
      extraocular muscle enlargement, scleral thickening, eyelid thickening, optic
      nerve thickening, orbital fat density increasing, lacrimal gland enlargement,
      sinusitis, subperiosteal abscess, ring-enhancement in masses, etc. CONCLUSION:
      All these findings on CT are of important significance for the diagnosis of
      orbital inflammatory lesions.

PMID- 9590831
TI  - [A study of corneal transplantation and human leukocyte antigen matching].
AB  - OBJECTIVE: The effect of human leukocyte antigen (HLA) matching on immune
      rejection after keratoplasty was studied. METHODS: Immunoserologic HLA typing was
      performed on thirty-three eyes with corneal vascularization of 33 high-risk
      patients before keratoplasty, and HLA matching was made before the surgery. The
      donor corneas used for these cases were selected on the basis of obtaining a
      negative HLA cross-match test and matched ABO antigen compatibility of blood
      group before surgery. The mean follow-up was fifteen months. RESULTS: The
      findings suggested that there should be highly statistic significance (t = 7.36,
      P < 0.01) between the rate of rejection of well matched group and that of the
      poorly matched one. There was no correlation between the number of HLA antigen
      matched and the rejection rate (t = 0.917, P > 0.05). CONCLUSION: Lower incidence
      of corneal graft failure from allograft rejection occurs when well HLA matching
      is used for selecting donor in high-risk patients with corneal vascularization.

PMID- 9590832
TI  - [An observation on calcium ion overloaded injury and the effect of calcium
      channel blocker in rabbit retina under acute ocular hypertension].
AB  - OBJECTIVE: In order to observe the retinal injury by Ca+2 overload under ocular
      hypertension and the effect of verapamil treatment. METHODS: Atomic absorption
      spectrophotometry and phosphate pyroantemonate (PPA) means were used to observe
      the changes of rabbit retinal Ca+2 content and the therapeutic effects of
      verapamil under this situation. RESULTS: In the ocular hypertensive group, Ca+2
      increased from the moment of intraocular pressure elevation, and with
      prolongation of time, it tended to increase steadily. In comparison with the
      control group, there were significant differences (P < 0.01). PPA showed that the
      longer the time, the more obvious swollen the mitochondria and much more calcium
      deposition in the mitochondria. In the group of rabbits with ocular hypertension
      having taken verapamil treatment, the Ca+2 content was markedly lower, the
      changes of mitochondria milder and the Ca+2 deposition in mitochondria less than
      that of the ocular hypertension group without treatment. CONCLUSION: Calcium
      overload may be one of the reasons of retinal injury under ocular hypertension,
      while calcium-blocker may alleviate this injury.

PMID- 9590833
TI  - [Anterior chamber associated immune deviation inhibiting experimental autoimmune
      uveoretinitis].
AB  - OBJECTIVE: To study the inhibition of occurrence and development of experimental
      autoimmune uveoretinitis (EAU) by the induction of anterior chamber associated
      immune deviation (ACAID). METHODS: All animals (guinea pigs), except controls,
      were pretreated with anterior chamber injection of allogeneic retinal extract to
      induce ACAID, and thereafter, they received intradermal footpad immunization of
      the same antigen in complete Freund's adjuvant (CFA) for induction of EAU, and
      dead pertussis bacilli were also subcutaneously injected as a second adjuvant.
      The pathological changes were investigated by light and electron microscopy.
      RESULTS: The incidence of EAU in experimental group was 25.0%, whereas 85.7% in
      the positive controls. CONCLUSION: ACAID does, to a great extent, inhibit the
      incidence and development of EAU.

PMID- 9590834
TI  - [An experimental study on corneal nerve regeneration after penetrating
      keratoplasty with long-term cryopreserved rabbit corneas].
AB  - OBJECTIVE: To observe the morphology of rabbit corneal nerve regeneration in the
      grafts after penetrating keratoplasty (PKP) with long-term cryopreserved
      homogeneous donor material. METHODS: Both long-term cryopreserved and short-term
      moist-chamber preserved fresh rabbit corneas were applied in the keratoplasty. By
      means of glyoxylic-acid induced fluorescence (GIF) and acetylcholine esterase
      (AChE) staining histochemical techniques, the morphological features of
      adrenergic and cholinergic nerve regeneration were monitored under light
      microscope in those grafts from ten days to eight months after surgery. RESULTS:
      During various intervals, the morphological changes of neural reinnervation were
      similar in the two groups, and numerous subepithelial nerves that showed random
      changes in direction and caliber were apparent. The nerve endings in the
      epithelium were few. CONCLUSIONS: The cryopreservative procedures do not affect
      neural regeneration under light microscope. The depressed tactile sensitivity
      following the surgery is correlated with nerve endings in the epithelium
      subnormal in number and with the regeneration of corneal nerves abnormal in
      distribution and morphology.

PMID- 9590835
TI  - [New phase of the clinical and basic study on corneal diseases in China].

PMID- 9590836
TI  - The healing of excimer laser ablated cornea and the effects of corticosteroid.
AB  - OBJECTIVE: To investigate the wound healing of the cornea following 193 mm
      excimer laser photorefractive keratectomy (PRK) and the effects of corticosteroid
      on it. METHODS: PRK was performed on both eyes of 6 monkeys. Corticosteroid was
      given to the right eyes, but not to the left ones. At 4 days, 1 week, 2 weeks, 1
      month, 3 months and 6 months, corneal pachymetry was examined and the eyes of one
      monkey were enucleated and the corneas were stained immunohistochemically for
      collagen type III, type IV and type VII, fibronectin and laminin. RESULTS: The
      expression of collagen type Vii recovered to the normal linear patter at 1 month.
      With corticosteroid, the deposition of collagen type III and fibronectin was
      markedly reduced and the pachymetry of central cornea was closer to the expected
      value. CONCLUSION: This study suggests that corticosteroid help to minimize the
      postoperative myopic regression and corneal haze after PRK.

PMID- 9590837
TI  - [Assay of anti-corneal endothelial antibody after penetrating keratoplasty].
AB  - OBJECTIVE: To study the effective materials in the immune response and the
      humoral immunity in graft rejective reaction in the host after penetrating
      keratoplasty (PKP). METHODS: PK was performed on 2 groups of monkeys with a 5.5
      mm button in a 5.0 mm bed. The heterogroup (human to monkey) had 4 monkeys, and
      homo-group (monkey to monkey) also 4. Nelken's method was modified. Two kinds of
      antigens, corneal endothelial and stromal antigens, had been made the first time.
      Enzyme linked immunosorbent assay (ELISA) was used to detect the anti-corneal
      endothelial antibody (ACEAb) in the serum and aqueous humor of the host. RESULTS:
      After PKP, the anti-corneal stromal antibody did not increase obviously, while
      the increase of ACEAb was distinct. CONCLUSION: Humoral immune response can occur
      in the host after PK, and the effective material is ACEAb.

PMID- 9590838
TI  - [A study on the course of corneal epithelial healing in diabetic rabbits].
AB  - OBJECTIVE: In order to approach the course of corneal epithelial healing of
      diabetes mellitus. METHODS: The experimental rabbit diabetes models were produced
      by the injection of alloxan. The corneal epithelium of each rabbit was removed by
      freezing with a 6 mm diameter brass probe cooled in liquid nitrogen. The rate of
      corneal epithelial healing following freezing in the normal rabbit was compared
      to that in the diabetic one. Contrasted with the normal rabbits, the
      ultrastructural changes of the epithelium with and without freezing were also
      observed in the diabetic rabbits. RESULTS: It is shown that there is no
      statistical significant difference in the overall rate of epithelial healing
      between the normal and diabetic rabbit. In contrast with the normal rabbit, the
      epithelial basement membrane of the diabetic rabbit without freezing revealed
      markedly thickened, and the mitochondria and glycogen particles in the epithelial
      cell increased. In the diabetic rabbit with freezing, the epithelial basement
      membrane appeared absent or discontinuous. After complete healing, the corneal
      epithelium was edematous in diabetic rabbit. CONCLUSION: The abnormal basemenet
      membrane and edematous epithelial cell were responsible for the diabetic corneal
      epithelial poor healing and recurrent erosion.

PMID- 9590839
TI  - [A study on histochemistry and electron microscopy of corneal nerves in
      experimental diabetic rabbits].
AB  - OBJECTIVE: To observe the changes of corneal nerves in diabetes mellitus.
      METHODS: Alloxan-induced diabetes in rabbits was used as the experimental model.
      Histochemical techniques and electron microscopy were applied to examine the
      corneal nerves. RESULTS: In the diabetic rabbits, from 6 weeks, the density of
      nerve plexus became markedly sparser, the fibers thinner and the activity of
      nerves lower than those of the control group. Ultrastructural changes showed
      swelling of axons, irregular distribution of fibril and degeneration of
      mitochondria of varying degree; with the progress of disease the above changes
      became more marked gradually. CONCLUSION: The abnormal corneal nerve changes
      might be a pathologic basis for the reduction in corneal sensitivity in diabetes.

PMID- 9590841
TI  - [Corneal endothelial decompensation of iridocorneal endothelial syndrome treated
      by penetrating keratoplasty].
AB  - OBJECTIVE: To evaluate the effect of penetrating keratoplasty in treatment of
      iridocorneal endothelial syndrome. METHODS: The clinical and pathologic
      evaluation records were retrospectively analyzed for 8 cases with iridocorneal
      endothelial syndrome treated by penetrating keratoplasty. Postoperatively, they
      were followed for 3 months to 6 years. RESULTS: Seven cases had visual
      improvement, five buttons kept being transparent and three buttons became opaque.
      CONCLUSIONS: The penetrating keratoplasty is an effective measure for treatment
      of corneal endothelial decompensation of iridocorneal endothelial syndrome.
      However, the successful operative rate of this syndrome is lower than that in
      cases with corneal leucoma without vascularization.

PMID- 9590840
TI  - [Comparison of various types of imidazole derivatives for treatment of
      filamentous fungal keratitis].
AB  - OBJECTIVE: 73 eyes of 73 patients with filamentous fungal keratitis were treated
      by various types of imidazole derivatives. METHODS: The mean patient age was 36
      (range, 15-62) years. The areas of corneal ulcer were 2-4 mm x 2-5 mm. The
      hypopyon was 1-3 mm in height. The patients were randomly divided into 4 groups:
      I 23 eyes were treated by 1% miconazole suspension. II 15 eyes by imidazole mixed
      oil (i.e. econazole and miconazole in castor oil). III 19 eyes by dusting mixed
      imidazole powder onto focal corneal lesions. IV 16 eyes by focal corneal lesion
      resection combined with dusting mixed imidazole powder. RESULTS: The cure rates
      were 21.74%, 66.67%, 73.68% and 93.75%, and the average days of treatment were
      65, 68, 35 and 19, respectively, in the 4 groups. The differences in the cure
      rates and in the means of treatment durations between each of the former three
      groups and the 4th group are remarkable (P <0.01). CONCLUSION: Focal corneal
      lesion resection combined with dusting mixed imidazole powder is relatively
      effective in treatment of filamentous fungal keratitis.

PMID- 9590842
TI  - [A study of high-pass resolution perimetry in the early diagnosis of primary open
      angle glaucoma].
AB  - OBJECTIVE: To evaluate the application of high-pass resolution perimetry (HRP) in
      detecting the early visual field loss of glaucoma. METHOD: According to the
      method described by Frisen, we developed HRP in a personal computer. The HRP was
      used to examine the visual field of 22 normal subjects (44 eyes), 27 cases (41
      eyes) of primary open-angle glaucoma (POAG) with abnormal automated visual fields
      and 10 cases (13 eyes) of early POAG or suspected POAG with normal automated
      visual fields. RESULTS: The mean resolution threshold in the normal subjects was
      3.96+/- 0.55db in the right eyes and 3.98+/- 0.55dB in the left eyes. It is
      demonstrated that HRP was more sensitive than automated perimetry in detecting
      the glaucomatous visual field defects, its sensitivity was 93.75% and specificity
      was 97.7%. The early visual field loss of glaucoma might present increment of the
      retinal resolution threshold. CONCLUSION: HRP is a relatively sensitive method
      for the detection of the early visual field loss in POAG, and it can be used
      extensively.

PMID- 9590843
TI  - [The features of color pattern electroretinogram in early primary open-angle
      glaucoma].
AB  - OBJECTIVE: To observe the features of the changes of color pattern
      electroretinogram (CP-ERG) in early primary open-angle glaucoma (POAG). METHOD:
      The detection and analyses of CP-ERGs in 29 patients (48 eyes) with POAG, 10
      patients (16 eyes) with ocular hypertension and 33 age-matched normal volunteers
      (48 eyes) were made. RESULTS: The changes of CP-ERG in early POAG included
      reduction of amplitudes of P1 and N2 waves, prolongation of the peak times of
      red/black N2 and blue/black P1 waves. Part of the patients with ocular
      hypertension had the amplitude of N2 wave reduced. Five factors including the
      amplitude of blue/black N2 wave, the amplitudes of red/black P1 and N2 waves, the
      peak time of red/black N2 wave and the white/black P1 to N2 wave amplitude ratio
      from CP-ERG which are significantly correlated to the diagnosis of early POAG
      were selected by the multiple factor stepwise discriminatory analysis, and the
      stepwise discriminatory function was set up. CONCLUSIONS: CP-ERG is a useful
      method in detecting the retinal functions in early POAG, and is helpful to its
      early diagnosis.

PMID- 9590844
TI  - [Vitreous surgery for subretinal neovascular membrane and hemorrhage].
AB  - OBJECTIVE: To study the indications, techniques and therapeutic effects of
      vitreous surgery for subretinal neovascular membranes. METHODS: 6 cases of
      subretinal neovascularization and subretinal hemorrhage were treated by
      vitreoretinal surgery. The surgical techniques consisted of three port pars plana
      vitrectomy, intraocular laser, retinotomy, subretinal neovascular membrane
      resection or hemorrhage removal, air-fluid exchange, etc. The pre and post
      operative examinations included fundus fluorescein angiography (FFA), Humphry
      visual field to evaluate the therapeutic effects of the surgery. RESULTS: The
      postoperative follow-up ranged from 4 to 7 months. The visual acuities of 4 cases
      improved, 0.3 or over in 2 cases and unchanged in 2 cases. CONCLUSION: Subretinal
      operation may be a safe and effective method to treat subretinal
      neovascularization if the indication was well mastered.

PMID- 9590845
TI  - [New flexible open-loop anterior chamber lens in secondary implantation].
AB  - OBJECTIVE: To determine the efficacy of new flexible open-loop anterior chamber
      intraocular lens (AC IOL) in secondary implantation. METHOD: Secondary AG-IOL
      implantation in 35 eyes including 28 with traumatic cataract and 7 with senile
      cataract was performed 3 months to 2.5 years after primary cataract extraction.
      All patients were followed up for at least 6 months. RESULTS: Of the 35 eyes, 27
      (77.1%) had a final visual acuity of 0.5 or better and 11 (31.4%) had 1.0 or
      better. CONCLUSION: New flexible open-loop AC IOL is safe and effective for
      secondary IOL implantation.

PMID- 9590846
TI  - [Cataract surgery in very long axial myopia].
AB  - OBJECTIVE: The incidence, refractive characters, operative results and the
      situations of intraocular lens (IOL) implantation in a series of eyes with very
      long axial length (> or = 27.00 mm) were analyzed. METHODS: According to the
      measurements of preoperative axial length and the degree of implanted IOL, the
      eyes with lengths of 27.00 mm or more selected from 1,000 eyes of consecutive
      senile cataract surgery were included in this group. The eyes requiring + 3.00D
      or more IOL were implanted with IOL. Simple extracapsular cataract extraction was
      performed on eyes requiring <+3.00D or negative lens. The postoperative follow-up
      was 20.0 +/- 8.5 months. RESULTS: There were 81 eyes in this group with a range
      of axial length of 27.00-34.71 mm and an average corneal curvature of 43.91 +/-
      1.81D. The range of IOL power for these eyes was +11.30-11.57D (mean, +2.10 +/-
      5.41D). The average axial length of 39 eyes with IOL implantation was 28.04 +/-
      0.68 mm and their postoperative corrected visual acuities (PCVA) in 82.1% of eyes
      were 10/20 or more. The average length of 42 eyes without IOL implantation was
      31.68 +/- 1.47 mm and the PCVAs in 42.9% of the eyes were 10/20 or more.
      CONCLUSIONS: The myopia with very long axial length is quite common in China. Its
      operative complications are not frequently seen. The cause of its poor PCVA is
      due to its pathologic changes in the fundus and the PCVA becomes worse as its
      axial length is increasing. An IOL with negative power is sometimes necessary for
      a myopic eye with very long axis.

PMID- 9590847
TI  - [Determination of visual function after implantation of intraocular lens].
AB  - OBJECTIVE: To understand whether the binocular visual function could be restored
      after posterior chamber intraocular lens (IOL) implantation. METHODS: The visual
      function including corrected vision, simultaneous perception, fusion,
      stereoacuity, aniseikonia and retinal correspondence point were determined for 50
      cases (64 eyes) after the surgery. RESULTS: The corrected visual acuities were
      0.6 or better. Visual acuities of 1.0 or better were achieved in 65% and 0.6-0.9
      in 35% of the eyes. All patients obtained simultaneous perception and fusion
      function. The near stereoacuity of 50 cases showed foveal stereoacuity < or = 60
      seconds in 23 cases (46%), macular stereoacuity 80-200 seconds 10 cases (20%) and
      peripheral stereoacuity 400 seconds 17 cases (34%). The far stereoacuity of 50
      cases comprised 34 cases of foveal stereoacuity (68%), 9 cases of macular
      stereoacuity (18%) and 7 cases of peripheral stereoacuity (14%). The
      postoperative retinal correspondence points were normal. There was no aniseikonia
      in 35 cases, except 15 cases of aniseikonia which was within normal tolerable
      limits. CONCLUSION: When binocular corrected vision is > or = 0.4 with ocular
      alignment, the binocular visual function could be restored for varying degrees.

PMID- 9590848
TI  - [Apparent accommodation in pseudophakic eyes after implantation of posterior
      chamber intraocular lenses].
AB  - OBJECTIVE: To study the question about apparent accommodation in pseudophakic
      eyes after implantation of posterior chamber intraocular lens (IOL). METHODS: The
      distant and near vision, refraction, pupillary size and shape, the depth of
      anterior chamber before and after mydriasis of 68 patients (73 eyes) with rigid
      posterior chamber IOL implantation were examined when the correcting lenses were
      worn, their powers of apparent accommodation were measured by HS-9D Accommod
      Polyrecorder. RESULTS: The mean value of apparent accommodation was 1.53 +/-
      0.59D. There was a negative correlation between apparent accommodation of
      pupillary diameter (r = -0.62). The apparent accommodation in the group with
      normal pupillary movement is greater than that in the group with abnormal one. A
      mean change of anterior chamber depth, 0.4 mm, before and after mydriasis was
      found. It appears that rigid posterior chamber implants do move backward on
      ciliary muscle relaxation. There was a positive correlation between apparent
      accommodation and the degree of IOL movement (r = 0.47). No significant
      correlation was found between apparent accommodation and the anterior chamber
      depth before mydriasis and age (r = 0.26, r = 0.22), etc. CONCLUSION: The
      apparent accommodation is the result of the change of focus depth in the eye
      which is caused by the cooperation of several factors such as corneal
      astigmatism, pupillary size and movement, etc. So optimal postoperative myopic
      astigmatism and good pupillary movement are beneficial to apparent accommodation
      in an eye with posterior chamber IOL implantation.

PMID- 9590849
TI  - [Pathological examination of 10 eyes with silicone oil injection].
AB  - OBJECTIVE: To find the histopathologic findings about 10 eyes of 10 patients with
      silicone oil injection. METHODS: The operative procedures included retinal
      detachment surgery, pars plana vitrectomy and silicone oil injection. The globes
      were enucleated 4 to 27 months after silicone oil injection. Paraffin sections
      were made for light microscopic examination. RESULTS: The retina showed severe
      degeneration, pre- and sub-retinal membranous fibrous tissue proliferation. The
      round empty vacuoles formed by silicone oil could be seen in the proliferative
      membrane. CONCLUSIONS: It is demonstrated that silicone oil has great toxic
      effect to the detached retina and it may stimulate the development of
      proliferative vitreoretinopathy.

PMID- 9590850
TI  - [The structure and type of neuroglia in human eye lamina cribrosa].
AB  - OBJECTIVE: To investigate the morpho-structure of neuroglia in the lamina
      cribrosa of human eyes, its cell type, physiological characteristics and role in
      the pathological process of optic nerve damage. METHODS: Histochemical and
      immunocytochemical staining, and transmission electron microscopic techniques
      were uses. RESULTS: The neuroglial tissue is distributed in the interspaces
      between the laminar sheets, on the internal wall of scleral canal and in optic
      nerve fiber bundles. Its cell is of fibrillary neuroglial astrocyte type.
      CONCLUSION: The fibrillary neuroglial astrocytes constitute a spatial net-work
      like architecture within the lamina cribrosa, provide mechanical support for
      optic nerve fibers as their main function and have higher resistance to pressure
      insults than optic nerve fibers.

PMID- 9590851
TI  - [An experimental study of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in
      aqueous humor after intraocular lens implantation].
AB  - OBJECTIVE: The tumor necrosis factor (TNF) and interleukin-1 (IL-1) levels in
      aqueous humor after intraocular lens (IOL) implantation were studied in rabbit
      eyes and their effects on post-operative anterior ocular inflammation were
      discussed. METHODS: 27 adult pigmented rabbits were divided into three groups:
      (1) Lens extraction and intraocular lens (IOL) implantation in the capsular bag.
      (2) Simple extracapsular lens extraction, and (3) normal control group without
      surgical intervention. Aqueous humor samples were aspirated on days 1, 3, 7 and
      14 postoperatively. A modified double-antibody indirect sandwich ELISA was used
      to detect for the presence of TNF. MTT colorimetry was used to detect for the
      presence of IL-1. The data were analysed statistically. RESULTS: TNF and IL-1
      levels in the aqueous humor were significantly higher (P < 0.05) at 1, 3, 7, and
      14 days postoperatively in IOL implanted group than that in the control group,
      and TNF levels in aqueous humor at 3, 7 and 14 days postoperatively and IL-1
      levels at 1 and 3 days postoperatively were significantly higher (P < 0.05) in
      IOL implanted group than that in simple extracapsular lens extraction group (P <
      0.05). In the postoperative 7-14 days, the TNF and in the 3 to 14 days the IL-1
      in the aqueous humor reached their maximum levels in IOL implantation group.
      CONCLUSIONS: It is reasonable to consider that the increases of TNF and IL-1
      levels may play critical roles in the anterior ocular inflammation response after
      IOL implantation.

PMID- 9590852
TI  - [A new technique for isolation of photoreceptor layer].
AB  - OBJECTIVE: If somebody wants to start the research of photoreceptor
      transplantation, first of all, the pure photoreceptor layer should be obtained.
      The pure photoreceptor is the key of retinal transplanting experiment for
      accurate analyses and good results. We present the pure photoreceptor layer
      isolation technique. METHOD: A vibratome, a special machine for tissue and cell
      isolation, was used for retinal isolation and pure photoreceptor cells were
      harvested. RESULTS: The pure photoreceptor cell layers of mice, rats, rabbits,
      monkeys and human have been obtained by this new technique. CONCLUSIONS: By the
      technique, 100 per cent of pure photoreceptor cells could be isolated, and the
      manipulation is simple and reliable.

PMID- 9590853
TI  - [Prospects of eye plastic surgery in China].

PMID- 9590854
TI  - The repair of eyelid defect with free hard palate mucosal autograft.
AB  - OBJECTIVE: To investigate the free hard palate mucosal autograft as a new
      replacement in eyelid reconstruction. METHODS: (1) Animal experiment, 12 eyelid
      defects from 3 dogs were repaired with hard palate mucosal autograft, and after
      operation they had excellent eyelid appearance. The findings of pathological
      examination, the morphology and thickness of epithelium are the same as its
      original. The cells and vascularization in the connective tissue are normal. The
      arrangement of collagen fiber bundles is regular. (2) Clinical practice, 15
      eyelid defects from 13 eyes included 3 upper eyelids, 8 lower eyelids and 2 of
      both upper and lower eyelids. 5 cases were of malignant tumor and 8 cases of
      trauma. 6 eyelids were of total defect, 4 eyelids of two-third defect and 5
      eyelids of a half to one-third defect. The ages ranged from 22 to 79 years old.
      We used the intermediate split thickness of hard palate mucosal autograft to do
      the eyelid reconstruction. All the cases were followed for an average of 11.3
      months after the reconstruction. RESULTS: 8 eyelid defects were cured, 3 were
      improved significantly and 4 improved. No severe complications were found.
      CONCLUSION: The hard palate mucosal autograft acts not only as a palpebral
      supporting tissue but also forms palpebral conjunctiva.

PMID- 9590855
TI  - [An experimental study on compound anisodine III for softening scar of mouse skin
      after burn].
AB  - OBJECTIVE: The aim of this study was to investigate the mechanism of compound
      anisodine (CA) III which can rapidly soften the cicatrized tissue in clinical
      practice. METHODS: 2 mol/L NaOH was applied onto the back of 36 mice for one
      minute to induce deep grade skin burn injury. After 1 week local cicatrization
      occurred. The mice were randomly divided into 3 groups: 1 ml saline was used in
      group I as control, hyaluronidase 150 U dissolved in 1 ml 2% procaine was used in
      group II and 0.005% CA 0.1 ml in 2% procaine 1 ml with hyaluronidase 150 U was
      used in group III. Subcutaneous injection once every other day for two weeks was
      the method of drug administration in all the 3 groups and then all the rats were
      euthanized. The burned skin was sectioned for HE and modified Masson's stains.
      RESULTS: Histopathology revealed there were epidermis proliferation,
      keratinization and fibrosis with disorderly arranged collagenous fibers invading
      into muscles and a large amount of inflammatory cells infiltrating the lesion in
      groups I and II. However, the skin was nearly normal in group III. CONCLUSIONS:
      CA III can inhibit the epidermic and collagenous proliferation, improve the
      tissue blood supply and have antiinflammatory effect to prevent scar formation
      and promote epidermic repair in the skin.

PMID- 9590856
TI  - [Orbital rim reconstruction with coral porous hydroxyapatite].
AB  - OBJECTIVE: To search for the effect and safety of coral porous hydroxyapatite
      (CHA) implanted material in orbital rim reconstruction. METHODS: 7 cases of
      orbital rim reconstruction were treated with CHA which is a plate form mass with
      an interconnected system of canals of approximately 200 microns in size. It has
      three types: 1.0 cm x 1.5 cm x 5.0 cm, 0.6 cm x 1.5 cm x 5.0 cm and 0.4 cm x 1.5
      cm x 5.0 cm. According to the shape of a contralateral healthy orbit, a rubber
      putty model was made before the operation. An incision was designed at the upper
      1/3 of the face for the elimination of wrinkles or a prolonged incision of lower
      lid bag plastic surgery was made. After the exposure of the defective part of the
      orbit, a correctly molded CHA tamponade was inserted. RESULTS: The orbital rim
      reconstruction in 7 cases with orbital defect was successfully treated with CHA.
      During a follow-up of 3-12 months (average 6.6 months), there was no extrusion or
      migration of implant. CONCLUSION CHA is a good material for substitution of bone
      graft and is much better than autogenous tissue of other artificial materials.

PMID- 9590857
TI  - [Clinical application of a new mobile integrated orbital implant].
AB  - OBJECTIVE: To improve the socket reconstruction after enucleation. METHODS:
      Hydroxyapatite (HA, made in China) was made into a porous HA sphere and wrapped
      up in the scleral shell as a mobile integrated orbital implant. It was applied to
      43 patients with enucleation and anophthalmia, The surgical technique is
      described. RESULTS: All sockets have been corrected very well and the prosthetic
      mobility and the cosmetic appearance are excellent. After a follow-up of 6 to 24
      months, no migration or extrusion of the implant or infection occurred.
      CONCLUSION: It is considered that at present this new mobile integrated orbital
      implant is made of one of the best materials and this method of socket
      reconstruction is one of the best method for selection.

PMID- 9590858
TI  - [Orbital exenteration associated with cavity reconstruction].
AB  - OBJECTIVE: A surgery was designed for the cosmetic improvement after orbital
      exenteration. METHODS: Exenteration associated with simultaneous or secondary
      orbital reconstruction was performed on 22 patients, including transplantation of
      temporalis muscle in 11 cases, temporoparietal fascia with vascular pedicle in 10
      cases and latissimus dorsi myocutaneous free flap in one case. RESULTS: Except 7
      patients who needed palpebral resection and orthopedic operation the second time,
      all of them were fitted well with ocular prostheses postoperatively and obtained
      satisfactory cosmetic results. CONCLUSION: Among the three methods of orbital
      reconstruction, the temporoparietal fascia transplantation is the best.

PMID- 9590859
TI  - [Experimental research and clinical application of homologous dura mater in
      ocular plastic surgery].
AB  - OBJECTIVE: To explore the clinical value of the dura mater implantation in ocular
      plastic surgeries. METHODS: Alcohol preserved homologous dura mater was implanted
      into the upper fornix under the conjunctiva of rabbit eye and light, electron
      microscopic histological and immunological examinations were made for the
      implant. 38 eyes consisting of 30 eyes of blepharoptosis, 4 eyes of blepharo
      coloboma, 3 eyes of hollow socket and 1 eye of teleepicanthus were treated by
      homologous dura mater implantation. RESULTS: In the follow-up periods ranging
      from 1.5 to 2.5 years, 26 eyes in the treated eyes were cured, 9 eyes were
      markedly improved, 3 eyes failed. Histological findings showed that after 1 week
      of implantation there was cell infiltration around the implant, at 2 weeks new
      collagenous tissue developed at the margin of the implant and 2-3 months after
      transplantation, the grafts were replace by the patient's own connective tissue.
      The histological examination of 3 failure cases showed that the cause of the
      failure was due to the ischemia of homograft. The results of unidirectional mixed
      lymphocyte culture showed that the stimulation index before implantation in
      comparison with that at 96 and 120 hours after implantation had statistical
      significant differences, while in comparison with that at 144 hours after
      implantation had no such difference. Before the implantation, the stimulation
      index of the lymphocyte culture at 96 hours was significantly different from that
      at 144 hours statistically (P < 0.05). In the comparison of specific killing
      activity before and after implantation, there was statistical significant
      difference. CONCLUSION: The effects of transplantation of homologous dura mater
      employed in ocular plastic surgeries of blepharoptosis, blepharocoloboma,
      teleepicanthus and hollow socket are fairly good.

PMID- 9590860
TI  - [Epicanthoplasty during double-fold eyelid operation].
AB  - OBJECTIVE: In order to achieve an artistic epicanthoplasty and gain an ideal
      eyelid double-fold parallel to the lid margin. METHODS: Various epicanthoplasty
      procedures were performed on 183 patients. Combining Fox's plastic operation for
      correcting upper lid type epicanthus and "L" form removal of skin for correcting
      lower lid type epicanthus, we put forward three kinds of methods available for
      epicanthoplasty. According to the degree of seriousness of upper lid type
      epicanthus, the patients who had a strong desire to receive treatment or improve
      their looks underwent different operative procedures. The skin resection in 38
      cases was of shuttle-form and in 120 cases, of cuneiform: low level "Z"-plasty
      was performed on 25 cases. RESULTS: Satisfactory cosmetic results were obtained
      in 183 cases. CONCLUSION: These methods of plastic surgery can achieve artistic
      epicanthoplasty in double-fold eyelid operation.

PMID- 9590861
TI  - [Secondary intraocular lens implantation in children].
AB  - OBJECTIVE: The study was designed to determine the visual outcome and indication
      of secondary posterior chamber intraocular lens (IOL) implantation. METHODS: The
      operation was performed on 34 eyes with aphakia in children after separation of
      posterior iris synechia from posterior capsule and formation of a posterior
      chamber space large enough to insert an intraocular lens. Based on whether the
      integrity of the posterior capsule was complete or not, various techniques of
      secondary IOL implantation were adopted. RESULTS: The follow-up periods ranged
      from 6 to 24 months. The results showed that 29 of the eyes (85.29%) achieved a
      post-operative corrected visual acuity equal to or better than that of the best
      corrected visual acuity before the surgery; the postoperative uncorrected visual
      acuities in 16 eyes (47.06%) and corrected visual acuities in 28 eyes (82.35%)
      reached 0.5 or better. CONCLUSION: Secondary posterior chamber IOL implantation
      is a safe and effective method in children who have a complete or partial
      posterior capsule.

PMID- 9590862
TI  - [An analysis of posterior capsular rupture in cataract surgery].
AB  - OBJECTIVE: To analyze the incidence, features and related factors of posterior
      capsular rupture (PCR) in extracapsular cataract extraction, the main
      intraoperative complication impairing the procedure of intraocular lens (IOL)
      implantation. METHODS: The PCR including zonular break and vitreous loss was
      recorded according to the stage of operative procedure in 757 eyes with senile
      cataract (the average age was 67.3 +/- 8.3 years). RESULTS: There were 51 eyes
      (6.7%) with PCR and 42 eyes (5.5%) of them accompanied with vitreous loss. The
      PCR in 17 eyes (33.3%) occurred during manual expression of the nucleus, 25 eyes
      (49.0%) in the course of aspiration of the cortex, and 9 eyes in the subsequent
      manipulations. Except the unexpected damage to the posterior capsule, the main
      factors were: smaller incision for the nucleus expression, lens dislocation
      during capsulotomy, small pupil in the course of cortex aspiration, high pressure
      from the posterior chamber and traction on capsular bag when removing anterior
      part of the cortex. CONCLUSION: Intraoperatively, the prevention of PCR and
      improvement of management ability are very important for the IOL I-stage
      implantation.

PMID- 9590863
TI  - [Observations on early stage intraocular pressure after modern extracapsular
      cataract extraction].
AB  - OBJECTIVE: To observe the early intraocular pressure (IOP) after extracapsular
      cataract extraction (ECCE). METHOD: ECCE was performed on 58 eyes which were
      randomly divided into 3 groups, and postoperatively, at various intervals the IOP
      was measured and compared. RESULTS: The low IOP was not measurable by tonometer
      at 1 hour after the operation. At postoperative 3 hours, the mean IOP was higher
      than that of the preoperative level. The peak of IOP elevation was between
      postoperative 6-12 hours, over 2.80 kPa (1 kPa = 7.5 mmHg) and > or = 4.0 kPa
      were in 31 eyes (53.45%) and 4 eyes (6.90%) respectively, and the highest IOP was
      4.40 kPa. Naturally, the levels of IOP resumed normal in all cases in
      postoperative 24 hours. The IOPs in 5 eyes (8.62%) were lower than the normal
      level (< 1.33 kPa) within 72 hours after the operation. The postoperative IOP of
      the group with diamox administered preoperatively was lower than that of the
      group with either mannitol or without drugs (P < 0.05) to lower the IOP
      preoperatively. The eyes with normal postoperative IOP accounted for the
      majority. CONCLUSION: Preoperative oral administration of diamox is a measure to
      prevent the early elevation of IOP after ECCE.

PMID- 9590864
TI  - [Domestic silicone oil, removal and complications].
AB  - OBJECTIVE: To master the optimal time of domestic silicone oil (DSiO) removal
      after vitreoretinal surgery and to observe the complications after it removal.
      METHODS: DSiO removal was performed through a superior corneoscleral limbus or
      pars plana incision in 64 cases. RESULTS: The rate of the attached retina was
      85.5% after DSiO removal. The visual acuity was improved or unchanged in 53 cases
      (82.8%). In 27 cases followed up postoperatively for an average of 11.6 months,
      the retina remained attached in 18 cases (66.7%). The postoperative complications
      included retinal redetachment in 12 cases and intraocular hemorrhage in 4 cases.
      CONCLUSION: 3-6 months after operation is the best time for removing DSiO when
      retinal tears are healed and DSiO is not emulsified.

PMID- 9590865
TI  - [Quadrant pattern visual evoked potential in normal eyes].
AB  - OBJECTIVE: The study was designed to approach the difference in pattern visual
      evoked potential (PVEP) among quadrants of the normal eye. METHODS: Quadrant
      transient PVEP method was used to record quadrant PVEP for 70 eyes of 35 normal
      subjects. RESULTS: The latency of P100 in lower temporal and lower nasal fields
      was significantly shorter than that in upper temporal and upper nasal fields; the
      amplitude of P100 in lower temporal and lower nasal fields was significantly
      higher than that in upper temporal and upper nasal fields. Generally, in lower
      field, the P100's latency is shorter and its amplitude higher. CONCLUSION: The
      difference in P100 between upper and lower field of normal person is possibly
      related to the fact that the lower field is used more frequently than the upper
      in ordinary human or animal life, and to the differences in distribution of
      retinal ganglion cells and in retina-cortex pathway between the upper and lower
      retina.

PMID- 9590866
TI  - [A clinical analysis on 131 senile cases with diplopia].
AB  - OBJECTIVE: To approach the pathogenic features of senile diplopia to elevate the
      rate of accurate clinical diagnosis and the therapeutic effect of treatment.
      METHODS: Prism, synoptophore, Hess' screen and red glass test were used to
      examine the ocular position, muscle movement and diplopia image in 131 cases
      (aged 60 or older). Biochemical examination of blood and imaging diagnosis were
      also involved. RESULTS: Among 131 cases, 120 (91.6%) suffered from binocular
      diplopia and 11 cases (8.4%) monocular diplopia. The majority of cases (110/120)
      with binocular diplopia were of ocular dyscinesia type resulting from
      intracranial vascular diseases, while the majority of cases with monocular
      diplopia resulted from complications of intraocular operation. CONCLUSIONS: Most
      of the diplopia in the aged are binocular one whose main cause is ocular
      dyscinesia resulting from vascular diseases. The cause of monocular diplopia in
      most of the cases is frequently due to the complications of intraocular
      operation. The authors emphasize a thorough examination of patients with
      diplopia.

PMID- 9590867
TI  - [An analysis of diagnostic errors of uveal melanoma].
AB  - OBJECTIVE: The causes of erroneous clinical diagnosis of uveal melanomas were
      studied METHODS: 18 cases with uveal melanoma diagnosed clinically were analyzed
      by clinical and histopathological methods. RESULTS: The main causes of the
      misdiagnosis were the opaque media to prevent from a clear view of the fundus in
      some cases, and clinicians' insufficient experience and ignorance of the case
      history. The histological bases of the misdiagnosis were suprachoroidal
      hemorrhage, subretinal hemorrhage and hemorrhage beneath retinal pigment
      epithelium, organization and formation of scar tissues. CONCLUSION: It is
      necessary to take the fluorescein angiography preoperatively and perform local
      resection of tumor on suitable cases.

PMID- 9590868
TI  - [Electrophoretic determination of aqueous and serum neuron-specific enolase (NSE)
      in the diagnosis of retinoblastoma].
AB  - OBJECTIVE: Neuron-specific enolase (NSE) or isoenzymes containing gamma-enolase
      are considered valuable in the diagnosis of tumors of neuroectodermal origin.
      METHOD: We used rapid electrophoretic method on cellulose acetate plate to
      determine the patterns of enolase isoenzymes in the 21 aqueous humor and 23 serum
      specimens from 23 patients with retinoblastoma (Rb) and 21 aqueous and 25 serum
      specimens from 25 control cases to evaluate NSE in the diagnosis of RB. The assay
      allowed assessment of all three major isoenzymes (alpha alpha, alpha gamma, and
      gamma gamma), and NSE relative activity and its percentage in the total relative
      activity of the three enolase isoenzymes were assessed by means of a fluorometer.
      RESULTS: Aqueous from all patients with Rb contained alpha alpha, alpha gamma,
      and gamma gamma isoenzymes and presented strong positive, the positive rate of
      NSE being 100% and its relative activity accounting for 45 +/- 9% of the total
      relative activity of the 3 enolase isoenzymes; no enolase was detectable in the
      control aqueous with cataract, glaucoma and Coats's diseases (4 cases), but in
      two patients with traumatic hyphema alpha alpha band, while the sera faint alpha
      gamma and gamma gamma presented in the aqueous. The control serum contained only
      an alpha alpha band, while the sera from patients with RB contained alpha alpha,
      alpha gamma and gamma gamma bands in 18 of 23 specimens, the positive rate being
      78.2%, and only alpha alpha bands in the rest 5 specimens (21.8%). In the
      patients with Rb, the NSE relative activity and its percentage in the total
      relative activity of the 3 isoenzymes in serum (36 +/- 9%) were significantly
      lower than that in aqueous. CONCLUSION: The amounts of NSE significantly in both
      serum and aqueous from patients with Rb, and the immunoelectrophoretic assay for
      determination of enolase patterns is valuable in the diagnosis and differential
      diagnosis of Rb. In addition, the method is rapid, simple and requires only a
      little among (< 5 microliters) of sample.

PMID- 9590869
TI  - [A study on relationship between glutathione S-transferase mu gene deletion and
      senile cataract susceptibility].
AB  - OBJECTIVE: To study the relationship between glutathione S-transferase mu (GST
      mu) gene deletion and senile cataract (SC) susceptibility. METHOD: Polymerase
      chain reaction (PCR) method was used to investigate the rates of GST mu gene
      deletion in 59 cases with SC and 112 healthy controls. RESULTS: The rate of GST
      mu gene deletion in cases with SC was 69.5% which was significantly higher than
      that of the controls, 50.9% (P < 0.05). An analysis stratified by smoking and
      nonsmoking showed that GST mu gene deletion rate in smoking subjects with SC was
      higher. Because of the small sample size of this study, although the rate of GST
      mu gene deletion in smoking subjects with SC has reached 72.4%, that is not
      significantly different from that of the controls statistically (P > 0.05).
      CONCLUSION: SC correlates with GST mu gene deletion and GST mu gene deletion is
      one of the hereditary factors for susceptibility to SC.

PMID- 9590870
TI  - [Pterygium and lipid peroxidation].
AB  - OBJECTIVE: The mechanism of light damage causing pterygium was investigated from
      the point of view of lipid peroxidation. METHODS: 22 patients with pterygium
      underwent excision of pterygium and a little superior bulbar conjunctiva was
      excised as normal control. The lipid peroxidation reaction of both pathologic and
      normal samples was analyzed by measuring the concentration of malondialdehyde.
      RESULT: The concentration of malondialdehyde in the pathologic samples was much
      higher than that in the normal samples (P < 0.01). CONCLUSION: Light Induced
      peroxidation reaction is closely related to the pterygium formation.

PMID- 9590871
TI  - [The relationship between the retinal lipid peroxidation or antioxidation and age
      in rats].
AB  - OBJECTIVE: To investigate the relationship between the retinal lipid peroxidation
      (LPO) or antioxidation and age. METHODS: The thiobarbituric acid (TBA) and
      chemical luminescence methods, were used to detect the retinal malondialdehyde
      (MDA) content produced by LPO and superoxide dismutase (SOD) activity which
      represents the antioxidation ability of retina in 22 rats different ages.
      RESULTS: The retinal MDA contents were 0.18 +/- 0.06, 0.16 +/- 0.06, 0.38 +/-
      0.11, 0.49 +/- 0.09 nmol/mg protein respectively in 5, 12, 18, 24 months old (F
      test, P < 0.01); the retinal SOD activities were 0.99 +/- 0.30, 2.48 +/- 0.56,
      0.70 +/- 0.35, 0.85 +/- 0.57 U/mg protein respectively in 5, 12, 18, 24 months
      old rats (F test, P < 0.01). CONCLUSIONS: The retinal MDA content increased and
      SOD activity decreased with aging. The cumulative effects of the long-term
      photochemical damage and decreased antioxidation ability in retina might be the
      causes of the increased retinal LPO.

PMID- 9590872
TI  - [An experimental study on epikeratophakia].
AB  - OBJECTIVE: The study was designed to investigate the corneal changes at various
      times after epikeratophakia performed on rabbit cornea. METHODS: The process of
      epithelial repair, or interlayer healing, the changes of endothelial cells and
      Langerhans cells (LC) in corneal epithelium were observed at different intervals
      after surgery by using histochemistry technique. RESULTS: The epithelial repair
      of the graft was completed by 4-12 postoperative days. The repopulation of
      keratocytes was seen firstly at peripheral and superior part of the lenticule at
      7-14 postoperative days and completed to normal by postoperative 2 months. No
      changes were observed in the endothelial cells. The proliferation of LC was
      observed in the limbal epithelium at day 3, reached the peak by day 14 and
      recovered to normal at month 2 postoperatively. CONCLUSION: Epikeratophakia is
      available and safe, The proliferation of LC might result from wound healing not
      from immune rejection.

PMID- 9590873
TI  - The influence of dietary sugars and starch on the establishment of Streptococcus
      mutans and Actinomyces viscosus in dental plaque of specific pathogen-free rats.
AB  - The establishment of S. mutans together with A. viscosus was investigated in
      dental plaque of specific pathogen-free (SPF) rats fed different carbohydrate
      diets. Two Tanzanian S.mutans strains MM3 and MM24 and one Tanzanian A. viscosus
      strain MM13 were used for this purpose. The basic diet consisting of 32% skim
      milk, 7% yeast extract and 1% soy bean oil was supplemented with either 10%
      lactose and 50% corn flour, or 10% glucose and 50% corn flour, or 60% amylum or
      60% wheat flour. S. mutans and A. viscosus were enumerated twenty days after
      inoculation. S. mutans counts were high irrespective of the dietary regime. A.
      viscosus counts in the glucose, lactose and amylum groups were of the same
      magnitude and significantly higher than those of the wheat flour group. The
      hypothesis that the establishment of S. mutans in sucrose free diets could be
      facilitated by the extracellular polysaccharides produced by A. viscosus was not
      supported by the present data. The finding that S. mutans can establish in high
      number in dental plaque of SPF rats in the absence of sucrose corroborates
      previous reports indicating high S. mutans counts in African populations with a
      low sucrose intake.

PMID- 9590874
TI  - Occlusal survey in a group of Tanzanian adults.
AB  - The aim of this study was to describe the occlusion pattern among Tanzanian
      adults. A total of 906 subjects aged 19-84 years from Ilala District, in Dar es
      Salaam were clinically examined. The variables studied included molar occlusion,
      overjet, overbite, open bite, crossbite, crowding, spacing and diastema mediale.
      Most of the subjects, 94%, had Angle's Class I molar occlusion. Transversal
      occlusal anomalies were rare. Spacing was more prevalent than crowding. Diastema
      mediale occurred in 32% of the subjects. Anterior open bite and spacing were the
      most prevalent conditions in the study group. Although crowding was prevalent,
      the results indicate an optimal sagittal occlusion with spacious maxilla and
      mandible. The frequencies found in this study were of a different pattern when
      compared with those reported previously in different populations. This suggests
      the need for a more comprehensive inter-ethnic groups study to confirm the
      differences and examine their implications to clinical and anthropological use.

PMID- 9590875
TI  - HIV infection in children: a challenge to dental practice.
AB  - Human immunodeficiency virus infection in children is on the increase globally.
      Because of diagnostic difficulties of HIV infection in children, among other
      reasons, all children are suspects. As a result of new developments in the
      treatment of this condition, more people with HIV infection/AIDS will survive and
      require dental treatment on a long-term basis. Dental practitioners who treat
      children and adolescents are faced with increasing challenge of providing optimum
      oral health care for all youths regardless of their being infected with HIV or
      not. The paper presents the diversified roles dentists in African countries have
      to play owing to prevailing peculiar circumstances in their communities. They
      should not only be oral diagnosticians and oral health care providers, but also
      health educators and promoters, researchers, counsellors, and social workers. All
      oral health personnel particularly the dentist, must be well-learned to meet
      these demands. By discharging these duties effectively, the spread of HIV
      infection will be curbed, and both the oral health and the entire well-being of
      the child population will be enhanced.

PMID- 9590876
TI  - Opinions of dental students in Dar es Salaam (Tanzania) and in Kuopio (Finland)
      concerning studies and expectations for future career.
AB  - The aim of this study was to compare the social background, career choice and
      future plans of dental students in a developing country, Tanzania, and in an
      industrialized country, Finland. In Dar es Salaam 100 per cent (n = 25) and in
      Kuopio 95 per cent (n = 120) of all dental students participated in this study
      during the academic year 1990-91 by returning an anonymous questionnaire. The
      similarities that Tanzanian and Finnish dental students shared were related to
      their feelings and opinions about dental studies and stress. In both places,
      dental studies seemed to be perceived quite stressful. However, most of the
      students from both countries planned to pursue further studies after graduation.
      As future career options, teaching and research were preferred among the
      Tanzanian students (38 per cent), while the majority of Finnish students (56 per
      cent) planned to work in community service. The observed difference in the
      preferred career options was most probably due to differing practical
      opportunities for a graduating dentist in the two countries.

PMID- 9590878
TI  - The Robin sequence associated with partial maxillary duplication and multiple
      facial clefts: a case report.
AB  - A case is presented of a male child of recent Yugoslav immigrants born with
      bilateral facial clefts, bilateral cleft lip and palate and severe micrognathia.
      Dental evaluation at 2 years revealed a very prominent premaxilla with
      hypoplastic maxillary deciduous central incisors. The mandible was markedly
      retrognathic with the patient exhibiting drooling. Panoramic radiographs revealed
      the presence of all deciduous teeth in addition to a duplication of the right
      maxillary molar teeth.

PMID- 9590877
TI  - Lower lip position and incisor overjet in a 12-year-old Nigerian population.
AB  - Relationship between variation of overjet and different postural positions of the
      lower lip in 1,016, 12-year old Nigerians was investigated using a modified
      Jackson classification (1962). The range and mean overjet values tended to
      decrease as the extent of incisal coverage increased with statistically
      significant differences in lip positions. Overjet greater than 6 mm was
      consistently associated with 'trapped' lower lip. The results of this study also
      indicate that lower lip may provide inadequate lip coverage to the upper incisors
      when the overjet is greater than 7 mm.

PMID- 9590879
TI  - The measurement of anterior and posterior facial heights in a Nigerian
      population.
AB  - A biological norm for the facial heights of Nigerians has been established by
      cephalometric measurements. Except for lower posterior facial height (LPFH), the
      other measurements namely upper anterior facial height (UAFH), lower anterior
      facial height (LAFH) and upper posterior facial height (UPFH), are not age
      dependent.

PMID- 9590880
TI  - The effect of different extraction methods on the antiglycolytic and
      antiureolytic properties of Sorindeia warneckei--a Nigerian chewing stick.
AB  - Experiments were carried out to determine the best partition reagents for
      extracting the active biological agents in Sorindeia warneckei--chewing stick.
      Results show the Soxhlet extraction method to be the most effective.

PMID- 9590881
TI  - Distribution of mutans streptococci among Nigerian school children.
AB  - A group of 504 Nigerian school children with an average age of 13 years were
      included in this study. The children attended 4 schools in the Jos area, Plateau
      State, and Toro Local Government area of Bauchi State. Salivary levels of mutans
      streptococci in these children were estimated with the "Strip mutans" test.
      Mutans streptococci were found in 73% of the urban children and 65% of the rural
      ones. Compared to most known populations, the prevalence of mutans streptococci
      was relatively low (69%). On the other hand 45% of the children had high salivary
      levels of mutans streptococci (score 3, approximately > 10(6) per ml saliva).

PMID- 9590882
TI  - Panoramic radiographic study of mental foramen locations in Saudi Arabians.
AB  - A panoramic radiographic study was carried out on 404 dentate Saudi Arabians, to
      locate positions of the mental foramen. Results show that 83.7% of the mental
      foramen locations occurred in the interdental space between the mandibular
      premolars and apical to the mandibular second premolar. 9.35% occurred posterior
      to the mandibular second premolar, and 6.95% occurred apical/anterior to the
      mandibular first premolar. In female Saudis, the most common location of the
      mental foramen was apical to the mandibular second premolar (45.9%), while the
      most common location in male Saudis was the interdental space between the
      mandibular premolars (45.5%). Asymmetry of the mental foramen location, which was
      observed in 15.6% of the cases, was observed more often in males (17.9%) than in
      females (12.3%).

PMID- 9590883
TI  - Oral health knowledge, attitude and behaviour of 12-year-old suburban and rural
      school children in Nigeria.
AB  - The aim of the study was to investigate the oral health knowledge, attitudes and
      behaviour of 12-year-old primary school children living in suburban and rural
      Nigeria. A total of 574 children mostly from low socioeconomic status were
      studied through questionnaires. Relatively high level of oral health knowledge
      and positive attitudes to prevention were found. Majority of suburban children
      (72.5%) cleaned their teeth with toothbrush and toothpaste while most of the
      rural dwellers (49.8%) used chewing sticks. Overall, 83.5 per cent of all the
      children had never visited the dentist despite the fact that most of them
      believed it was necessary to visit the dentist for check-up. It was concluded
      that oral health education programme should be targeted to the need of the
      communities.

PMID- 9590884
TI  - Oral hygiene practices and oral health knowledge in a population of Mozambican
      adults.
AB  - A study was carried out to assess the oral hygiene practices and dental knowledge
      by means of a questionnaire, in a group of 239 adults in Mozambique. Despite the
      relatively low educational status of the sample, the level of dental knowledge
      appeared satisfactory. However, there still exists a need for increasing the
      awareness of good oral hygiene in this population.

PMID- 9590885
TI  - A pilot study of periodontal disease awareness amongst Nigerians.
AB  - Two hundred and seventy-five Nigerian subjects were seen to assess their
      periodontal disease awareness and to correlate it with their periodontal status,
      using a screening index--Community Periodontal Index of Treatment Needs
      (C.P.I.T.N.). More than half of the subjects had visited the dental clinics in
      the past. The major reason for their visits was for relief of toothache and/or
      extraction. Although a high percentage claimed not to have gum disease, various
      stages of periodontal disease were observed in this group of subjects. The author
      advocates: (1) The introduction and use of periodontal index e.g. C.P.I.T.N. for
      easier examination of patients. (2) Refresher courses for dental personnel in
      periodontics, and (3) Use of the mass media such as electronic media to promote
      periodontal health awareness.

PMID- 9590886
TI  - Epithelial jaw cysts: analysis of 126 Nigerian cases.
AB  - One hundred and twenty-six Nigerian cases of epithelial jaw cysts were retrieved
      from case notes and biopsy records of the Department of Oral and Maxillofacial
      Surgery and Department of Oral Pathology and Oral Biology of the Lagos University
      Teaching Hospital. The cases were analysed for age, sex, site and methods of
      management. Results show that developmental odontogenic cysts (57.14%) were more
      common than inflammatory odontogenic cysts (26.94%). Dentigerous cyst (22.22%)
      was the most common epithelial jaw cyst, followed by radicular cyst (21.43%).
      Developmental non-odontogenic cysts were more than twice as common in females as
      in males. Sixty-eight per cent of epithelial jaw cysts were treated by
      enucleation, 10% by marsupialisation, 13% by jaw resection and 9% by surgical
      excision.

PMID- 9590887
TI  - Sintering flaws in Flexoceram inlay porcelain.
AB  - The development of processing flaws within Flexoceram inlay porcelain prior to
      fracture strength testing was assessed qualitatively. The firing procedure
      recommended by the manufacturer was used except for the end-firing temperature
      which was varied. Sintering for 10 minutes produced less porous samples which
      were better than the manufacturer's recommended time of 9 minutes.

PMID- 9590888
TI  - Effect of maternal protein deficiency during pregnancy and lactation on the
      organic matrix composition of the bone and skin of the sucklings of rat.
AB  - Effect of a staple Nigerian diet comprising of cassava flour, vegetable soup and
      fish, and containing 10% protein on bone and skin organic matrix of the offspring
      of rats fed the diet during pregnancy and lactation was studied. Two types of the
      diet were formulated. One contained 10% protein for the poor and the other 21%
      protein for the rich Nigerians. The two types of diet were dried at 70 degrees C
      for 24 hrs and ground into powder so that the rat could consume it. Laboratory
      rat chow was used as the control diet and it contained 21% protein. Each diet was
      fed to different groups of rats with water ad libitum during gestation and
      lactation. Chemical composition of the bone and skin matrix of the sucklings of
      the rats at 10 and 21 days of age were determined. The weights of the femur,
      humerus and skin as well as nitrogen, hexosamine and uronic acid concentrations
      in the bone and skin, and calcium concentration in the bone of sucklings whose
      dams were fed the diet containing 10% protein were lower than those of sucklings
      of dams fed diet containing 21% protein. Proline:Nitrogen and
      Hydroxyproline:Nitrogen concentration ratios in the bone and skin, and
      Calcium:Nitrogen concentration ratio in the bone were not affected by the level
      of dietary protein given to the dams. The quantity and not the composition of
      organic matrix constituents, collagen and chondroitin sulphate were reduced by
      maternal protein deficiency. Improper formation of bone matrix caused reduced
      calcification. It is concluded that the 10% dietary protein eaten by poor
      Nigerians is inadequate to support normal bone and skin weight and matrix
      composition of sucklings from dams consuming the diet.

PMID- 9590889
TI  - Epidemiological study of some factors related to deciduous tooth eruption.
AB  - This community based study evaluates the eruption pattern of the Saudi children
      (0-24 months), living in the North West region of the country. No child under the
      age of 6 months in this study had any teeth. The number of teeth acquired
      correlated strongly with age (r = +0.82, t = 18.7, p < 0.001), and moderately
      with weight (r = +0.63, t = 9.09, p < 0.001). Age and weight having independent
      effects on the timing of eruption of deciduous teeth. Before teething began, a
      threshold weight had to be acquired and female teeth emerged with comparatively
      lower weights than that of males of the same age. Even though age was highly
      correlated with the number of teeth erupted, the wide range of normal prevents
      delay in teething from being a useful index of inadequate growth in this
      community.

PMID- 9590890
TI  - Fractured anterior teeth among mentally handicapped school children in Ibadan,
      Nigeria.
AB  - Prevalence of fractured anterior teeth among 205 mentally handicapped school
      children in Ibadan, Nigeria is presented. A high prevalence of 20% was found and
      a higher proportion of females wes found to have fractured anterior teeth than
      males. The 13-15 years age group had the highest percentage prevalence. Tooth
      fractures occurred more in the upper jaw. Seizure disorders was found to be a
      statistically significant predisposing factor among this group of children.
      Management of these children depends on prevention as there are factors which may
      prevent the provision of good restorative care for this group of children.

PMID- 9590891
TI  - Clarification on the differential diagnosis of giant cell containing lesions of
      the oral and maxillofacial regions.
AB  - A broader overview of the essential differences and overlap in the histopathology
      and clinical presentation of giant cell containing lesions are discussed. This is
      an attempt to eliminate some confusions attendant to their diagnosis and possible
      prognosis. These lesions occur both intraosseously and extraosseously. Langhans'
      type giant cells have been shown not to be an exclusive preserve of tuberculoid
      granulomas but also of giant cell lesions. The osteoclast like lesions with the
      exception of giant cell tumour (GCT) are treated by local curettage while the
      latter is treated by radical resection.

PMID- 9590892
TI  - Variability in upper lip posture to overjet changes in 12-year-old Nigerian
      children.
AB  - One thousand and sixteen 12-year-old Nigerian primary school children were
      examined for upper lip posture at different overjet values. Upper lip positions
      were assessed using the Jackson's criteria. The most common lip position was
      Jackson class 3 with 72 per cent. Positions 0 and 1 were not common features.
      Normal overjet value of 2-4 mm was found in 82 per cent of the sample population.
      The findings from this investigation also showed very little significant
      relationship between variation of overjet at different upper lip positions.

PMID- 9590893
TI  - Evaluation of orthodontic treatment outcome: a personal clinical audit using the
      PAR index (peer assessment rating).
AB  - Although various methods have been used to evaluate orthodontic treatment
      outcome, the PAR index (Peer Assessment Rating) was recently developed for the
      purpose of assessing treatment standards. The purpose of this investigation was
      to evaluate the treatment standard of 52 consecutively treated cases during
      orthodontic postgraduate training (1991-1993). The pre- and post-treatment study
      models were collected and analysed using the PAR index. The mean age at start of
      treatment and the mean treatment duration was 13.6 (+/- 3.6) years and 15.9 (+/-
      4.5) months respectively. Dual-arch fixed appliance was the predominant form of
      treatment employed. A high treatment standard was achieved as indicated by the
      mean PAR score reduction of 82.6 per cent. Most of the cases (92.3%) showed
      varying degree of improvement. Of the 4 (7.7%) cases classified as "worse or no
      difference", three were treated with removable appliances. With the exception of
      buccal occlusions, treatment showed strong improvement on individual PAR
      components. The shortcomings of the method of assessment are also discussed.

PMID- 9590894
TI  - The effects of health education on patients' subsequent dental visits: a practice
      based research in health promotions.
AB  - We conducted a practice-based research project on health education (discharge
      counselling) in Gallatin, TN involving 280 patients for more than two and one
      half years. Half of the patients were randomly assigned to a "discharge
      counsellor" after receiving treatment from the dentist. A non-dentist office
      staff provided the discharge counselling. Patient compliance with treatment
      modalities and after-treatment dental instruction was the key element of this
      study. This study confirms that health education (discharge counselling) was
      effective in reducing the number of patients in this project who would revisit
      the dentists for (1) emergency treatment, (2) the same complaint as their initial
      complaint, (3) pain management, and (4) prescription refills. In this study,
      gender difference was not revealed as a factor, but racial difference might be a
      factor.

PMID- 9590895
TI  - In-vitro antibacterial effects of extracts of Nigerian tooth-cleaning sticks on
      periodontopathic bacteria.
AB  - Aqueous extracts from 8 plants used for tooth-cleaning in Nigeria were tested for
      their ability to inhibit the growth of five periodontopathic bacteria,
      Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum,
      Eikenella corrodens and Campylobacter rectus. Extracts of all the plants except
      that of Massularia acuminata exhibited varying growth inhibitory potentials on
      the microorganisms. Extract of Terminalia glaucescens showed the widest spectrum
      of activity, inhibiting the growth of all the tested bacteria except P.
      gingivalis. These findings corroborate other studies that the plants possess
      antiplaque properties and suggest that they may be useful tools in preventive
      dentistry in poor developing countries. However, the bioavailability of the
      active ingredients of the plants and their long term effects in vivo need to be
      investigated.

PMID- 9590896
TI  - Immunohistochemical localization of Epstein-Barr virus receptor on hyperplastic
      gingiva of kidney allotransplant patient immunocompromised by cyclosporin A.
AB  - The strong association between Epstein-Barr Virus (EBV) and certain tumours of
      the oro-maxillo-laryngeal region aroused our present interest. A pre-requisite
      for the molecular interplay of oncogenesis by EBV is the expression of the EBV
      receptor on the target cell of the host. As a possible contribution to this
      concept, we adopted immunohistochemical technique to examine a hyperplastic
      gingival tissue obtained from a subject on kidney allotransplant immunosuppressed
      with cyclosporin A (CSA). Our results demonstrate expression of EBV/C3d receptor
      on the superficial layers of the hyperplastic gingiva but absent in the
      basal/parabasal layers. It is suggested that the superficial layer expression of
      EBV/C3d receptor could be due to direct acquisition from the environment of the
      oral cavity rather than a systemic extension from the deep layers of the same
      epithelium.

PMID- 9590897
TI  - Saliva and salivary gland alterations in HIV infection: a review.
AB  - HIV-1 can be recovered sporadically from whole saliva and individual salivary
      gland secretions, but the concentration of virus, when present, is low. Saliva
      possesses antiviral activity, and although virus may be found in the mouth, the
      mouth is not a transmission route of HIV-1. After HIV-1 infection, salivary gland
      function is altered. Flow rates may decrease, and certain electrolytes and anti
      microbial proteins are elevated. A proportion of patients develop severe salivary
      gland disease. Most patients, however, maintain adequate salivary gland function
      and retain ability to produce antimicrobial proteins in saliva.

PMID- 9590898
TI  - Applications of trigeminal somatosensory evoked potentials in the investigation
      of unilateral lesion of the inferior dental nerve: report of 2 cases.
AB  - 2 cases were reported in which trigeminal somatosensory evoked potential (TSEPs)
      confirmed the presence of unilateral lesions of branches of the trigeminal nerve,
      and were used to predict the prognosis. The TSEPs allowed an accurate prediction
      of the prognosis. The first patient regained sensation on the numb side of the
      tongue as predicted from the TSEPs, whilst the TSEPs also predicted a poorer
      prognosis for the second patient, who might not regain sensation on the numb side
      of the tongue unless a successful nerve grafting was done. TSEPs could indeed be
      very useful in the management of lesions involving the trigeminal nerve, and
      especially in the follow-up investigations.

PMID- 9590899
TI  - Ectopic eruption of maxillary first permanent molar: a case report.
AB  - A case of unilateral ectopic eruption of maxillary first permanent molar with
      congenital absence of second premolar on the affected side is presented. The
      treatment of choice in this case, was extraction of the second deciduous molar to
      permit full eruption of the affected molar. A review of the prevalence, clinical
      and the radiographic presentation as well as different treatment modalities for
      this condition is provided.

PMID- 9590900
TI  - Temporo-mandibular joint pain dysfunction syndrome: report of two cases and
      review of literature.
AB  - Two cases of TMJ pain dysfunction syndrome were diagnosed and treated between
      1990 and 1992. The two cases occurred in females in the 4th decade of life. In
      the two cases, there was evidence of psychogenic origin but no evidence of
      organic origin. These cases are being presented because of the common psychogenic
      origin as aetiological factor in both cases and the quick response to treatment
      as soon as cause of the disorder was discovered.

PMID- 9590901
TI  - Examination of skin moles.
AB  - The extraoral and intraoral examination should be part of the clinician's
      examination process. During the extraoral portion, it is necessary to assess skin
      moles that may be present in the head/neck region or on other accessible skin
      areas. This review paper is a discussion of melanoma and provides information on
      evaluation of moles to determine need for referral.

PMID- 9590902
TI  - Strength of core build-up materials in endodontically treated teeth.
AB  - PURPOSE: To compare the in vitro strength of a reinforced glass ionomer and a
      light-cured glass ionomer used as an alternative to amalgam in core construction
      to restore endodontically treated mandibular molar teeth. MATERIALS AND METHODS:
      The root canals of 120 extracted human mandibular molar teeth were prepared
      chemomechanically and obturated with laterally condensed cold gutta-percha. The
      crown of each tooth was sectioned leaving only one cusp standing. Gutta-percha
      was removed from the pulp chamber in all teeth. The volume of the pulp chamber
      was measured and the teeth ranked in ascending order of chamber volume. The
      specimens were divided into six groups of 20, allocating teeth with similar
      chamber volumes into each group. In three of the groups, gutta-percha was removed
      from the coronal 3-4 mm of each root canal. The teeth were restored with one of
      three materials, a cermet cement (Ketac-Silver), a resin-reinforced glass ionomer
      (Vitremer), or amalgam (Contour). Core preparation was carried out after 48
      hours, reducing each core height to 6 mm. The specimens were thermocycled for 24
      hours and then mounted in dental stone. A control group of 20 unrestored human
      mandibular molars was mounted in cold cure acrylic. Each tooth was tested in a
      Nene machine with a compressive load applied at 90 degrees to the occlusal
      surface at a crosshead speed of 5 mm/minute. RESULTS: There was no statistically
      significant difference between the experimental groups (P > 0.05), but the
      control group was significantly stronger (P < 0.001). Extension of core material
      into the coronal root canal system did not increase the fracture resistance of
      any of the experimental materials. Regression analysis of the results revealed no
      correlation between the volume of the pulp chamber and the load to fracture.

PMID- 9590903
TI  - Effect of resin-modified glass ionomer cements on secondary caries.
AB  - PURPOSE: To evaluate the in vitro secondary caries inhibitory effect of two resin
      modified glass ionomer cements (R-GICs). MATERIALS AND METHODS: Class V cavities
      were prepared at the cementoenamel junction on facial and lingual surfaces of 32
      extracted upper premolars. The facial cavities were restored with a conventional
      glass ionomer cement (GIC) (Fuji II), while the lingual cavities were restored
      with either one of the R-GICs (Fuji II LC, Photac Fil, Vitremer), or a resin
      composite (Z-100). The margins of the restorations were subjected to a 20-day in
      vitro cariogenic challenge and the degree of demineralization was analyzed by
      microradiography. The amounts of fluoride released into distilled water from disc
      specimens of the materials tested were also measured for immersion time up to 161
      days. RESULTS: The R-GICs and GIC's released similar cumulative amounts of
      fluoride over 161 days. Photac-Fil showed significantly higher amounts of
      fluoride release over the same period. The depth of the outer lesion and the
      thickness of the acid-resistant layer showed no significant difference among the
      R-GICs and GIC's. Moreover, the residual fluoride and calcium in the dentin
      adjacent to the R-GICs and GIC's were correlated with the thickness of acid
      resistant layers in the dentin adjacent to the R-GICs and GIC's by electron probe
      microanalysis. However, the inhibitory effect of the R-GICs was not directly
      related to the fluoride concentrations eluted from them.

PMID- 9590904
TI  - Microleakage of dentin-bonded crowns placed with different luting materials.
AB  - PURPOSE: To assess the microleakage of dentin-bonded porcelain crowns placed with
      three different luting materials. MATERIALS AND METHODS: Standardized full
      coverage crown preparations were made on 45 extracted premolar teeth of a design
      which was considered typical of the minimal preparation indicated for dentin
      bonded crowns. Half of the margin of the crown was placed below the cemento
      enamel junction. Impressions of the prepared teeth were made and individual
      crowns constructed in feldspathic porcelain. The interior surface of each crown
      was etched with Mirage Superetch and treated with silane bond-enhancing solution.
      The crowns were cemented using one of the following combinations: Group A,
      Scotchbond Multi-Purpose Plus (SBMP)/3M Ceramic Luting Kit; Group B, Mirage
      ABC/FLC, and Group C, All-Bond 2/DuoLink. The teeth were stored for 2 weeks at 37
      degrees C, subsequently thermocycled, and the restorations examined for leakage
      using buffered methylene blue as the marker. The teeth were sectioned bucco
      lingually through the restoration and the degree of microleakage assessed
      microscopically. RESULTS: All groups showed leakage at the dentin and enamel
      margins and at the restoration-cement interface. There were significant
      differences in leakage at the enamel margins for the three groups (P = 0.007) but
      not at the margins finished in dentin (P = 0.762). There was a significant
      difference in leakage between Groups B and C at the enamel margin (P = 0.009)
      and, within Group B, significantly greater leakage at the enamel-restoration
      interface than the dentin-restoration interface (P = 0.033). There were no other
      significant interactions. At the restoration-adhesive interface there was no
      significant difference in leakage among the groups.

PMID- 9590905
TI  - Shear bond strength of a new one-bottle dentin adhesive.
AB  - PURPOSE: To test the shear bond strength of a new adhesive, 3M Single Bond, to
      dentin surfaces containing different degrees of moisture. Two commercially
      available one-bottle adhesives (Prime & Bond, One-Step) and a conventional three
      step system (Scotchbond Multi-Purpose Plus) were included for comparison.
      MATERIALS AND METHODS: 120 bovine teeth were embedded in acrylic and the labial
      surfaces were polished to 600 grit to create standardized dentin surfaces for
      testing. Resin composite was bonded to dentin using a gelatin capsule technique.
      Four adhesive systems were evaluated with three different degrees of surface
      moisture (moist, wet, and overwet). Shear bond strengths of adhesives to dentin
      were determined using a universal testing machine and analyzed by ANOVA and
      Tukey's post hoc tests. RESULTS: Single Bond had mean shear bond strengths of
      19.2, 23.2 and 20.3 MPa to moist, wet, and overwet dentin, respectively. Bond
      strengths of the three-component system Scotchbond Multi-Purpose Plus ranged from
      23.1 to 25.3 MPa, but were not significantly higher than the values for Single
      Bond. Prime & Bond had bond strengths similar to those of Single Bond, but One
      Step had significantly lower bond strengths (P < 0.05) in the wet and overwet
      conditions.

PMID- 9590906
TI  - Effect of finishing method on the microleakage of Class V resin composite
      restorations.
AB  - PURPOSE: To evaluate the effect of three finishing methods on the microleakage of
      Class V hybrid resin composite. MATERIALS AND METHODS: Facial and lingual Class V
      cavities were prepared at the cemento-enamel junction of bovine incisors.
      Restorations of the two materials (Z100; Prodigy) were placed, using the supplied
      dentin-adhesives (Scotchbond Multipurpose; OptiBond FL, respectively). Finishing
      methods were carbide (C) and diamond (D) finishing instruments operated at high
      speed, and finishing disks (S). After thermal cycling, the teeth were immersed in
      methylene blue dye, then sections of the restored teeth (n = 12) were visually
      assessed for leakage. RESULTS: No leakage was observed at the resin-enamel
      interface in any restoration. At gingival margins, the incidence of leakage
      (slight/severe) was: Z100 D = 4/3, C = 5/3, S = 2/0; Prodigy D = 3/0, C = 2/4, S
      = 3/2. The greatest incidence of leakage was observed in restorations finished
      with carbide finishing burs. A two-way ANOVA of leakage data rankings showed no
      significant difference among the three methods (P = 0.07) or between the two
      materials (P = 0.55), and no significant interaction of material and finishing
      method (P = 0.07).

PMID- 9590907
TI  - Bond strengths of the adhesive resin-amalgam interface.
AB  - PURPOSE: To evaluate the tensile and shear bond strengths of eight adhesives and
      two amalgams (spherical and lathe cut). MATERIALS AND METHODS: Two high-copper
      amalgams (Tytin, spherical; and ANA-2000, dispersed phase) and seven adhesives
      (Panavia EX, C&B Metabond, Chameleon Metal Resin Cement, All-Bond 2, All-Bond
      C&B, Photo-Bond and Imperva Dual) were evaluated. An epoxy resin (Stycast 1266)
      was included as a control for comparison because it was an adhesive material of
      similar viscosity but different chemistry from the dental adhesives. The aluminum
      surfaces were sandblasted with 50 microns aluminum oxide just prior to coating
      with adhesive resins. The testing area was defined with a 4 mm circular adhesive
      Mylar mask. All adhesives were mixed and handled according to manufacturers'
      instructions. Freshly mixed amalgam was condensed into the test cavity and onto
      the surface immediately after coating with adhesive. After 24 hours storage, the
      bond strengths were determined in an Instron testing machine at a crosshead speed
      of 2 mm/minute. The debonded surfaces were examined in an optical microscope for
      site of failure. The few samples which showed failure at the aluminum-resin
      interface were not included in the study. Selected debonded surfaces were
      examined by SEM. A 2-way ANOVA (General Levin Models-GLM) was used to analyze the
      data from both the tensile and shear bond strength tests. GLM was used instead of
      standard ANOVA because of the unbalanced design. The lack of balance occurred
      because some of the bonding resin/amalgam groups had different sample numbers.
      RESULTS: A wide variation in bond strengths was obtained with adhesive resin
      cements and not all appeared suitable for adhesive amalgam restorations. Panavia
      EX, C&B Metabond, Chameleon Metal Resin Cement and All-Bond C&B showed the best
      potential for amalgam bonding, with shear and tensile bond strengths greater than
      8 MPa. Viscous, filled versions of adhesives appeared to be more effective.
      Choice of amalgam appeared to be less important than choice of adhesive.

PMID- 9590908
TI  - Bond strengths of a new dentin adhesive system.
AB  - PURPOSE: This in vitro study evaluated the shear dentin bond strengths of EBS, a
      new three-component adhesive system containing an aqueous primer. Two other
      adhesive systems (Scotchbond Multi-Purpose and OptiBond FL) were included in the
      study for comparison. A simple tensile test and the effect of composite
      restorative material on shear bond strength were also evaluated. MATERIALS AND
      METHODS: Eighty bovine teeth were obtained, embedded in acrylic, polished to 600
      grit to form standardized dentin specimens, and randomly assigned to eight
      treatment groups. Resin composite was placed in gelatin capsules and bonded to
      dentin using the three adhesive systems. Each system was used according to
      manufacturers' instructions on dentin that was blotted to remain moist after
      etching. Each bonding system was used with its own manufacturer's composite
      material, and EBS and OptiBond FL were also used with a higher modulus composite,
      Z100. Specimens were stored in water for 24 hours, and bond strengths were
      determined using an Instron universal testing machine. RESULTS: EBS/Pertac II had
      a mean shear bond strength of 17.2 MPa, which was significantly less than
      Scotchbond Multi-Purpose/Z100 (22.5 MPa) but similar to OptiBond FL/Herculite
      (16.4 MPa). Shear bond strengths of EBS and OptiBond were only slightly higher
      when they were used with Z100 composite. Tensile bond strengths were less than
      shear bond strengths but were nearly identical for all three systems (range: 8.0
      9.8 MPa).

PMID- 9590909
TI  - Handling characteristics of a gallium alloy triturated with alcohol.
AB  - PURPOSE: To assess the handling characteristics of a gallium alloy triturated
      with one drop (10 microL) of ethyl alcohol and compare them to those of a high
      copper amalgam. MATERIALS AND METHODS: A commercial gallium alloy (Gallium Alloy
      GFII) and a high-copper amalgam (Tytin) were used. Ten dentists each restored
      four identical MO preparations in acrylic typodont teeth (two for each material).
      Each restoration was immediately evaluated by the operator for placement,
      condensation, proximal contact, carving, and resistance to fracture during matrix
      removal and overall quality according to a method used previously. The rating
      scale for each criterion ranged from 1 (very poor) to 5 (very good). Scores for
      each criterion for the amalgam and gallium alloy restorations were statistically
      compared. RESULTS: The gallium alloy tested was still rated significantly worse
      (P < or = 0.05) than amalgam for placement, condensation and carving but there
      were no significant differences in scores for other criteria. The dentists judged
      the handling of the gallium alloy in all criteria as fair to good and evaluated
      it as better in placement, condensation and establishment of proximal contact
      compared to a previous study, mainly because the pre-set material was no longer
      sticky.

PMID- 9590910
TI  - Effect of two fluorescent dyes on color of restorative materials.
AB  - PURPOSE: The objective of these two studies was to determine whether the use of
      dyes in vitro would affect the shade of tooth-colored restorative materials.
      MATERIALS AND METHODS: Two separate studies were performed. In Study 1, four
      groups (N = 36) of restorative materials; (1) resin composite (RSN), (2) resin
      modified glass ionomer (RMGI), (3) conventional glass ionomer (CGI), and (4)
      porcelain (PCN), were subjected to a rinse in either tap water (control) or
      Pyrromethene 556 dye at a concentration of 0.01M for 30 seconds or 0.0015 M for
      60 seconds. They were then rinsed with 25% ethanol as would be done in clinical
      usage. In Study 2, the same restorative materials (except PCN) were subjected to
      a rinse in either tap water (control) (N = 8) or 0.0018 M sodium fluorescein (N =
      8) for 60 seconds followed by a 5-second rinse with tap water. For both studies
      the specimens were analyzed for overall color changes (delta E*) comparing
      baseline to immediately post dye exposure and then again after 1, 4, 24, and 48
      hour storage under running tap water. In addition, an image of each specimen,
      illuminated under an argon laser light (HGM), was captured with a miniature
      charged-coupled device (CCD) color camera at the same time intervals when the
      color was measured. These images were analyzed for fluorescence using computer
      assisted methods. A software program then computed the mean and standard
      deviation of the fluorescence values for each image. The data were analyzed using
      repeated measures ANOVA. RESULTS: delta E* values from baseline on specimens
      treated with either Pyrromethene 556 or sodium fluorescein were not significantly
      different from water at any time. The only exceptions were CGI specimens exposed
      to 0.01 M Pyrromethene 556 and RMGI exposed to sodium fluorescein which had a
      higher delta E* immediately after treatment, however this effect was reversed
      after 1-hour rinse. Mean delta E* was less than 2.69 for specimens treated with
      Pyrromethene 556 and less than 3.20 for specimens treated with sodium fluorescein
      after 1-hour rinse in water. When the mean fluorescence level, as determined by
      the computer, was averaged there was no difference between the Pyrromethene 556
      treatments and control for RMGI, RSN and PCN after 4-hour rinse in water and, as
      time in storage increased, the fluorescence level decreased. CGI treated with
      0.01 M Pyrromethene 556 was significantly more fluorescent even after 48-hour
      rinse in water. All specimens treated with sodium fluorescein were also
      significantly more fluorescent than control even after 48-hour rinse in water. It
      was concluded that exposure of these restorative materials to Pyrromethene 556 at
      0.01 M or 0.0015 M or to 0.0018 M sodium fluorescein will not lead to any
      prolonged visually detectable color changes.

PMID- 9590911
TI  - Oral lichen planus update: clinical characteristics, treatment responses, and
      malignant transformation.
AB  - PURPOSE: To assess the current profile and the natural disease history of
      patients with oral lichen planus (OLP) and evaluate their responses to treatment.
      MATERIALS AND METHODS: Ninety-five community-referred patients with OLP, who were
      examined in our Oral Medicine Clinic between May 1995 and August 1996, comprised
      the study group. RESULTS: The OLP patients had been followed for 1-20 years (mean
      6.1). The average age at first-recognized onset was 59 years, and there was a 2.3
      to 1 female predominance. Only five of the patients knew of a family history of
      lichen planus. There were no evident associations with smoking, candida, systemic
      disease or medications. Of the 222 involved mucosal sites, the buccal mucosa was
      involved most often (79%) and the erosive form was most frequent. Of 70 patients
      who received systemic and/or topical corticosteroid treatment for pain (83%) or
      annoying irritation (17%), all but five obtained complete or satisfactory relief.
      A squamous cell carcinoma developed at a lesion site in three patients (3.2%)
      during the observation period.

PMID- 9590912
TI  - Effect of peroxide bleaches on fluoride release of dental materials.
AB  - PURPOSE: To investigate the effect of two bleaching agents, 35% hydrogen peroxide
      (Superoxal) and 10% carbamide peroxide (Opalescence), on the release of fluoride
      from Ketac-Fil, a glass ionomer cement, Photac-Fil, a glass ionomer/resin hybrid;
      and Tetric, a resin composite with fluoride. MATERIALS AND METHODS: Seven disks
      (9 x 3 mm) of each material were immersed in Superoxal for 1 hour to simulate an
      in-office application; seven other disks of each material were immersed in
      Opalescence 1 hour daily for 7 days to simulate a week of home bleaching regimen;
      and seven additional disks of each material without bleach served as a control.
      The disks were kept in deionized water and the water was tested for fluoride
      released every 24 hours for 14, 21, 28, and 35 days, respectively. RESULTS:
      Repeated measures ANOVA showed that the mean daily release of fluoride did not
      differ significantly (P > 0.05) between the bleaching agents or the control:
      Superoxal 6.17 ppm, Opalescence 6.45 ppm, and control 6.50 ppm. Statistically
      significant differences (P < 0.05) occurred for mean daily fluoride (+/- standard
      error) released from the three materials over the 35-day period: Photac-Fil 12.31
      +/- 0.48 ppm > Ketac-Fil 7.07 +/- 0.66 ppm > Tetric 0.12 +/- 0.01 ppm,
      respectively.

PMID- 9590913
TI  - Acute illness and recovery in adult female rats following ingestion of a tooth
      whitener containing 6% hydrogen peroxide.
AB  - PURPOSE: To determine whether ingestion of a tooth whitener containing 6%
      hydrogen peroxide as bleaching agent affected the gastric mucosa of adult, female
      laboratory rats. MATERIALS AND METHODS: Thirty-six fasting rats were intubated
      with a single bolus (5 g/kg body weight) of the tooth whitener Natural White
      which contains 6% hydrogen peroxide. Thirty-two control rats received deionized
      water. Rats were necropsied 15 minutes, 2 hours, 1 and 2 weeks after whitener
      ingestion. The gastric mucosa was examined histologically and blood hematocrit,
      glucose, BUN, and bilirubin measured. RESULTS: Six of the 36 rats died within 2
      hours of receiving whitener. Within 15 minutes of whitener ingestion, stomachs
      were grossly bloated with gas. Histological observation showed that gastric
      mucosal cells were vacuolated and gastric glands dilated. After 2 hours, gastric
      epithelial and glandular cells had sloughed off into the gastric lumen. Mean
      blood glucose and hematocrit were significantly (P < 0.05) elevated (233 +/- 41
      mg/ml and 50.5 +/- 0.9%) over mean control values (129 +/- 8 mg/ml and 42.8 +/-
      2.4%). Within 1 week, the stomachs of experimental rats were no longer bloated,
      the gastric mucosa appeared normal histologically, but mean blood hematocrit was
      significantly (P < 0.05) decreased (38.0 +/- 1.5%) from mean control value (43.3
      +/- 0.5%). There were no significant differences in mean blood values 2 weeks
      after whitener ingestion.

PMID- 9590914
TI  - Effect of enamel microabrasion on bacterial colonization.
AB  - PURPOSE: To determine if microabraded surfaces inhibit Streptococcus mutans
      colonization. MATERIALS AND METHODS: Ten extracted molars were obtained and
      sectioned in half mesio-distally. The mesial side was treated with microabrasion
      (PREMA Compound). The distal surface was designated as the control site. A
      plastic tube was secured on each surface with resin composite, exposing a surface
      of 13.2 mm 2. S. mutans 10,499 was cultured in TSB-YE supplemented with 5%
      sucrose and 2.5% glucose was added to each secured site in addition to 50
      microliters of cell suspension. Samples were incubated in a 5% CO2 chamber for 7
      days at 37 degrees C. Samples were taken from each site, incubated with
      dextranase (75 micrograms 1 ml), sonicated, and vortexed to disrupt cellular
      aggregates as much as possible. Samples were then plated on Mitis-Salivarius agar
      using a spiral plating system. Enumeration of numbers of colonizing bacteria was
      achieved following standard spiral plating system methodology. RESULTS: The mean
      for the microabraded group was 1.12 x 10(2) cfu/tooth and for the control it was
      1.15 x 10(4). Analyzing the data revealed a significant difference (P = 0.0188).

PMID- 9590915
TI  - A comparative study of anesthetic techniques for mandibular dental extraction.
AB  - PURPOSE: To compare the effectiveness of the intraligamentary technique of
      anesthetic administration (ILA) with the inferior alveolar nerve block (IANB) in
      extraction of mandibular teeth. MATERIALS AND METHODS: ILA and IANB injections
      using Citanest with Octapressin were administered on 16 patients requiring
      bilateral mandibular dental extractions. Discomfort during needle placement,
      profoundness of anesthesia obtained, and patient preference were evaluated for
      both techniques. RESULTS: A total of 45 teeth were extracted. Ten patients
      (62.5%) reported discomfort during needle placement with ILA injection compared
      to three patients (18.75%) with IANB (P = 0.031). Fifty percent (12/24) of teeth
      extracted with ILA injection were removed without discomfort to the patient
      compared to 85.7% (18/21) using IANB (P = 0.027). No difference in patient
      preference between the two techniques was noted.

PMID- 9590916
TI  - Surface treatment techniques for resin composite repair.
AB  - PURPOSE: To compare bond strengths of fresh resin composites to previously
      polymerized ("aged") composites following various surface treatments. MATERIALS
      AND METHODS: Eighty Pertac Hybrid (PH) and an equal number of Silux Plux (SLX)
      specimens were fabricated and stored for 1 week prior to surface treatment. The
      specimens were then polished and stored for an additional 24 hours prior to final
      surface treatment. The surface treatments included use of one of the following:
      (1) diamond bur (DB), (2) microetcher with 50 microns Al2O3@80 psi pressure (ME),
      (3) high-pressure air abrasion with 27 microns Al2O3@psi, (KCP), or (4) low
      pressure silicate ceramic deposition using 30 microns particles@34 psi (CJ-S)
      with a microetcher. Half of the samples were treated with a silanating agent.
      Fresh resin composite (same type as used for the aged specimen) was bonded to the
      treated surfaces, and specimens were then stored 24 h and thermocycled 300 x at 5
      degrees and 55 degrees C prior to testing for shear bond strength. Two-way ANOVA
      was used to determine significant differences between mean shear bond strengths
      for both composite materials. RESULTS: Significant differences were found between
      the groups for both surface treatment and silane use (P < 0.05). The interaction
      between the two main effects was also significant (P < 0.05). Overall, the
      highest bond strengths were found when the low-pressure silicate ceramic
      deposition system (CJ-S) was used, with or without silane.

PMID- 9590917
TI  - Marginal leakage of amalgam restorations pretreated with various liners.
AB  - PURPOSE: To evaluate and compare the microleakage of amalgam restorations lined
      with four different liners. MATERIALS AND METHODS: Cylindrical occlusal cavities
      were prepared in extracted human molars and the teeth were then divided into four
      groups and lined with one of four liners: Amalcoden, AM (glass-metal ionomer),
      FujiDuet, FD (glass ionomer), Amalgambond, AB (adhesive resin), or copal varnish,
      CV. Each cavity was then restored with a high-copper amalgam alloy and aged for 7
      days in 37 degrees C distilled water. The specimens were then thermocycled for
      300 cycles followed by immersion in 0.5% basic fuchsin dye solution for 24 hours.
      The teeth were then embedded in resin, sectioned, and dye penetration at the
      tooth/amalgam interface evaluated microscopically at x 100 and scored from 0 to 4
      (0 = no leakage and 4 = greatest leakage). RESULTS: The median values were: AM =
      1.0; FD = 0.5; AB = 1.1; and CV = 4.0. Statistical analysis using Kruskal-Wallis
      and Mann-Whitney U indicated no significant differences between AM and AB or FD
      and AB. CV was however, significantly worse at P < 0.01.

PMID- 9590918
TI  - Influence of environmental conditions on bond strength of a resin-modified glass
      ionomer.
AB  - PURPOSE: To investigate the influence of temperature and relative humidity (RH)
      on the dentin bond strength of a resin-modified glass ionomer cement (Fuji II LC)
      and to evaluate the bonding efficacy of dentin primer. MATERIALS AND METHODS:
      Four environmental conditions: (A) 25 +/- 1 degrees C, 50 +/- 5% RH, (B) 25 +/- 1
      degrees C, 95 +/- 5% RH, (C) 37 +/- 1 degrees C, 50 +/- 5% RH, (D) 37 +/- 1
      degrees C, 95 +/- 5% RH, were used to make the specimens. Bovine mandibular
      incisors were mounted in self-curing resin and the facial surfaces were ground on
      wet #600 SiC paper to expose dentin. Dentin Conditioner and OptiBond Prime were
      employed as treatment agents. After treating the dentin surface, the cement was
      condensed into a vinyl mold (4 x 2 mm) placed on the dentin and light cured. Ten
      samples per test group were stored in 37 degrees C water for 24 hours, then shear
      tested at a crosshead speed of 1.0 mm/minute. One-way ANOVA followed by Duncan
      test (P < 0.05) were done. RESULTS: The dentin bond strengths of the no
      conditioning group and Dentin Conditioner treatment group increased with
      increasing temperature but were not influenced by RH. With the use of the dentin
      primer, increased bond strengths and no influence of environmental conditions
      were observed. These data suggest the efficacy of employing dentin primer for
      application of the resin-modified glass ionomer cement regardless of temperature
      or RH.

PMID- 9590919
TI  - Bond strengths of resin-modified glass ionomers and polyacid-modified resin
      composites to dentin.
AB  - PURPOSE: To measure the shear bond strength of two resin-modified glass ionomers
      (Vitremer and Fuji II LC) and two polyacid-modified resin composites (Compoglass
      and Dyract) when applied to dry dentin, dentin supplied with water pressure from
      the pulp, and after thermocycling. MATERIALS AND METHODS: Ninety six extracted
      third molars were used. The root portion was removed just below the cemento
      enamel junction and the occlusal enamel was removed from the crown segment. An
      artificial root portion was made in Plexiglas, cemented to the crown segment and
      connected to a 36 cm. height water column. The tested materials were applied to
      the surface of dry dentin, dentin supplied with water pressure from the pulp, and
      after thermocycling. Shear bond strength was measured for the bonded specimens
      using an Instron at a crosshead speed of 0.5 mm/minute. RESULTS: There were no
      significant differences in bond strengths between Fuji II LC, Compoglass, and
      Dyract, which were significantly greater than that of Vitremer. The bond
      strengths of all materials were slightly increased or not affected by the
      presence of water pressure from the pulp. After thermocycling, the bond strengths
      of Fuji II LC, Compoglass, and Dyract were not significantly affected whereas
      those of Vitremer were significantly decreased.

PMID- 9590920
TI  - Interdiffusion of a traditional glass ionomer cement into conditioned dentin.
AB  - PURPOSE: To investigate whether a new auto-curing glass ionomer cement (Fuji IX)
      in combination with polyacrylic acid (Cavity Conditioner) forms an interdiffusion
      zone both under laboratory and clinical conditions. MATERIALS AND METHODS: Seven
      vital human posterior teeth were selected. A flat dentin surface was created on
      the buccal surface in order to apply the glass ionomer material. Seven other
      extracted human molars were prepared following the same procedure as with the in
      vivo experimental teeth. After extraction of the in vivo restored teeth, the
      samples were cut and prepared for hybrid layer observation under scanning
      electron microscope. RESULTS: An interdiffusion zone, of approximately 6 microns
      thick, was observed both under in vivo and in vitro conditions. At the interface
      between the two substrates, the interdiffusion zone was acid resistant and
      uniform.

PMID- 9590921
TI  - Resin bond strength with different methods to remove excess water from the
      dentin.
AB  - PURPOSE: To compare the resin bond strength using different methods to remove the
      excess water from the dentin while maintaining it moist. MATERIALS AND METHODS:
      60 human molars were randomly divided into four treatment groups of 15 teeth each
      as follows: Group 1: A wet bonding technique was used as recommended by the
      manufacturer and was used as a control group. The exposed occlusal dentin
      surfaces were conditioned with 32% phosphoric acid (Uni-Etch) for 15 seconds and
      rinsed for 15 seconds. 40 microL of distilled water was added to standardize the
      content of the water on dentin surface. The conditioned dentin surfaces were
      gently blow-dried for 3 seconds with oil-free compressed air. The tip of the
      syringe was placed at 2 cm from the dentin surface. One coat of the One-Step
      primer/adhesive was applied to the dentin surface using a fully saturated brush
      tip, allowed to remain on the surface undisturbed for 3 seconds, and then gently
      air-dried for 3 seconds from a distance of 1 cm to remove excess solvent and
      water. A second coat of the primer/adhesive was applied and gently air-dried from
      a distance of 1 cm. The primer/adhesive was light-cured for 10 seconds. Resin
      composite (Z100, shade A3) was then polymerized for 40 seconds. Group 2: The
      dentin surface was blot-dried by applying tissue paper (Kimwipes EX-L) adjacent
      to the exposed area; Group 3: The excess water on the dentin surface was removed
      using an applicator brush (Bend-a-Brush) for 5 seconds; Group 4: A small dry
      hydrophilic cotton pellet was gently applied over the dentin surface to remove
      the excess water. The sequential steps for these three groups were similar to
      those of Group 1. The dentin surface remained visibly moist in all procedures.
      After light-curing, the specimens were thermocycled (5 degrees and 55 degrees C,
      500 cycles, 30-second dwell time). The specimens were sheared and the data were
      analyzed using ANOVA and Tukey's test methods. The site of failure was analyzed
      using a stereomicroscope and a scanning electron microscope. RESULTS: ANOVA
      revealed that there was a statistically significant difference between the groups
      (P < 0.05). Turkey's test revealed that Group 1 was significantly lower than
      Groups 2, 3 and 4 with no difference between the last three groups (P < 0.05).
      All samples showed resin cohesive failures.

PMID- 9590922
TI  - A simple mathematical study of anterior dental relations. Part III: incisor and
      canine overbite.
AB  - Two previous articles described horizontal interarch relations with a simple
      model developed. This paper required further development of the horizontal
      relations to allow vertical overlap to be studied. An analysis of orthodontic and
      dental-prosthetic models provided values to refine horizontal description then
      guide vertical calculations. Tooth thickness and angles of the maxillary teeth
      were related to horizontal overlap to produce an estimate of potential overbite.
      Principles were derived from the calculations and stated. Change can be predicted
      for overjet and overbite during and after orthodontic treatment. This series of
      articles expands the logical foundations by rationally considering a broad range
      of anterior occlusions. There are limitations in observing one or two features of
      anterior occlusion without comprehending the influence of other significant
      measurements. Measuring change in anterior overbite is inadequate without
      concurrently accounting for changes of other variables such as:
      spacing/enlarging/hypodontia; crowding; buccal relations and tooth thickness. A
      better understanding of anterior dental relations is possible from use of this
      model and the principles derived from it.

PMID- 9590923
TI  - The similarity between parents and offspring in facial soft tissue: a frontal
      view study.
AB  - Similarities between parents and their offspring in facial soft tissue features
      were investigated. Fifty boys and fifty girls aged 9-10 years, excluding those
      with congenital anomalies, were selected. Frontal photographs of the family
      (father, mother and offspring) were taken and twenty-nine landmarks located on
      each enlarged tracing made from a photograph. Each landmark was digitised into
      (x, y) co-ordinate values from which the area and linear ratio dimensions were
      calculated and statistically evaluated. Results indicated that: (1) The nose was
      the feature that was most significantly correlated between parents and offspring.
      (2) The similarities between parents and offspring were closer for the relative
      positions of other features to the eyes than for individual features of the face.
      In general, the correlations between 'midparents' (the mean value of both
      parents) and offspring were higher than those between one parent and offspring.
      (3) The correlations between parents and offspring for size were higher than
      those for shape. (4) The similarities between mothers and offspring were closer
      than those between fathers and offspring. Furthermore: among four pairs of
      father/son, father/daughter, mother/son and mother/daughter, the mother/daughter
      pair had the highest correlation and the father/son pair had the lowest, which
      appears to be related to X-chromosome inheritance.

PMID- 9590924
TI  - An odontometric study of a Tibetan population.
AB  - Most of the indices of the norms of tooth dimensions established from model
      studies are those of a Western population. At present there are few norms for
      Oriental populations. This study was aimed at establishing more Oriental norms
      for various indices and the average tooth size of a particular Tibetan
      population, Tibetans being a distinct Mongolian type. The overall picture that
      emerges from all the established indices is that Tibetan teeth are broad and
      short. Mongoloids have a euryprosopic or wide face and a brachycephalic head.
      This study indicated that the teeth, dental arches and basal areas of the
      Tibetans in this group conform to this skeletal foundation.

PMID- 9590925
TI  - Lingual orthodontics: a review of its history.
AB  - When lingual orthodontics was first introduced about twenty years ago some called
      it the 'ultimate aesthetic appliance'. Patients and practitioners embraced this
      new treatment alternative with high expectations. Reports of disappointing
      results and high costs dampened much of the initial excitement and enthusiasm
      gradually waned. By the late 1980s, the number of practitioners using the
      technique had fallen sharply, leaving only a handful who still believed in its
      potential. Relatively little has been written on lingual orthodontics, almost
      nothing in recent years. This article takes an objective view of its present
      status.

PMID- 9590926
TI  - Orthodontic treatment planning for inclusion of the third molar in the dental
      arches: Part II.
AB  - Marked lower anterior crowding (late crowding or post-adolescent crowding) often
      develops at about the time of third molar eruption. Many studies have implicated
      the presence of third molars as a cause of this crowding. Despite the fact that
      there is no clear evidence that this is the case, many orthodontists and their
      patients' referring dentists routinely remove third molars at the retention stage
      of treatment to prevent crowding later; Ricketts et al. even advocate enucleation
      of the third molar while the patient is very young to prevent future crowding. In
      the following report on two orthodontically-treated patients (the first three
      cases in this report were published in The Australian Orthodontic Journal, Volume
      15, Number 1), the author emphasises the importance of careful consideration of
      the third molar in the treatment plan.

PMID- 9590927
TI  - Two-phase treatment of an Angle Class II division 2 malocclusion.
AB  - This case report describes a two-phase approach to the treatment of an Angle
      Class II division 2 malocclusion in a growing boy. The first phase utilised a
      functional appliance (Clark Twin Blocks) during puberty and achieved a pleasing
      improvement in the facial profile. The second phase involved a fixed upper and
      lower Begg appliance without extractions, followed by retention. An unexpected
      complication was the failure of the lower left second molar to erupt; surgical
      removal of cystic elements surrounding this tooth, followed by traction and,
      later, mechanics to correct the buccal cross-bite, eventually corrected its
      position.

PMID- 9590928
TI  - An in vitro test model for investigation of disinfection of dentinal tubules
      infected with Enterococcus faecalis.
AB  - The aim of the present study was to develop an in vitro test model from human
      teeth to comparatively examine antibacterial effectiveness of calcium hydroxide,
      parachlorophenol (PCP) and camphorated parachlorophenol (CPCP) against
      Enterococcus faecalis in infected root canals. Cylindrical dentin specimens were
      prepared from freshly extracted human maxillary anterior teeth. The specimens
      were inoculated with E. faecalis and then medicated with either CPCP, PCP or
      Ca(OH)2. The disinfecting efficacy of these agents was tested by collecting
      dentin chips from the inner ("canal") walls of the specimens and counting viable
      E. faecalis. The dentin chips were diluted and a classical bacterial count
      technique was used for recovery of E. faecalis strains of 5% sheep blood agar.
      The effectiveness of CPCP and PCP at one day was superior to the effectiveness of
      Ca(OH)2. In the three-day group, CPCP was the most effective, followed by
      Ca(OH)2. The experimental model used in this study may be useful for
      investigation of the effect of intracanal medicaments on microorganisms lodged in
      the root dentinal tubules.

PMID- 9590929
TI  - Bond strength between resin composite and etched and non-etched glass ionomer.
AB  - The authors evaluated, in vitro, the effects of etching glass ionomer cements
      prior to the application of a bonding agent and a resin composite on the bond
      strength of the glass ionomer/resin composite interface. Six glass ionomer
      cements were tested using the same bonding agent/resin composite system
      (Scotchbond Multipurpose/Z 100). For each material, 16 specimens were prepared
      and divided into two groups. Eight of the specimens were not etched while eight
      were etched with 37% phosphoric acid for 15 seconds. All the materials were used
      according to the manufacturers' instructions. Glass ionomer cylinders were
      prepared and were mounted in an assembly apparatus and the bonding agent/resin
      composite transferred to a demarcated area on the cement surface. The specimens
      were stored for 24 hours in distilled water at 37 degrees C and thermocycled.
      After thermocycling, the specimens were placed in a testing machine and a shear
      load applied with a knife-edged rod at the glass ionomer/resin composite
      interface. The shear bond strength was calculated and expressed in MPa. Data were
      analyzed by ANOVA and the Tukey-Kramer test. There were no significant
      differences among the shear bond strengths of the resin composite to etched and
      non-etched glass ionomer cements.

PMID- 9590930
TI  - Comparative in vitro study of apically extruded material after four different
      root canal Instrumentation techniques.
AB  - Forty newly extracted human upper central incisors were submitted to root canal
      instrumentation 1 mm from the apex using four different techniques: standard,
      step-preparation, crown-down, and ultrasound, with distilled and deionized water
      as the irrigating solution. The extrusion product was collected into a collecting
      device constructed for this purpose. Extrusion was calculated by the
      determination of the mass of extruded material. The step-preparation technique
      caused a larger amount of extrusion than the standard technique, which in turn
      caused greater extrusion than the crown-down and ultrasound techniques. All
      techniques used caused extrusion of material beyond the apical foramen.

PMID- 9590931
TI  - Cardiovascular alterations caused by the administration of 2% mepivacaine HCl
      with 1:20,000 levonordefrin (Carbocain) in dogs.
AB  - We studied possible cardiovascular effects (systolic, diastolic, mean arterial
      blood pressures, and heart rate) caused by intraoral infiltrative administration
      of 2% mepivacaine HCl with 1:20,000 levonordefrin in dogs (Canis familiaris),
      using a Beckman electrophysiograph. Doses used were 0.514 and 1.542 mg/kg body
      weight corresponding to one and three 1.8-ml cartridges, respectively, in 70-kg
      average weight adult men. A statistically significant increase was observed in
      the systolic and the mean arterial blood pressures.

PMID- 9590932
TI  - Occlusal splint therapy with a positioning orifice.
AB  - The authors studied the effect of a positioning orifice introduced in the
      anterior palatine region of occlusal splints for patients with craniomandibular
      disorders of swallowing and speech patterns. The patients were evaluated in four
      distinct situations. It was concluded that the splint orifice significantly
      favored swallowing and speech while the splint was being used, and is more
      comfortable for the patient.

PMID- 9590933
TI  - Similarities of periodontal clinical and microbiological parameters in mother
      child pairs.
AB  - The aim of this study was to verify the association between children and their
      mothers (N = 28) for periodontal clinical and microbiological measures.
      Periodontal clinical parameters (probing depth and bleeding on probing) were
      obtained from six reference teeth from each mother-child pair. In addition,
      subgingival plaque samples taken from the same reference teeth were collected and
      placed on the Perioscan test for the detection of Treponema denticola,
      Porphyromonas gingivalis and Bacteroides forsythus. There were statistically
      significant differences between children and mothers regarding probing depth;
      there was an overall tendency for mothers to exhibit average probing depths
      greater than their children. In contrast, if a child had a bleeding site, the
      respective site on the mother usually also bled on probing, implying that there
      was an association in terms of bleeding between the mother-child pairs. Similar
      findings were observed for the Perioscan test. It is concluded that the
      occurrence of bleeding and periodontal anaerobic infections (as determined by the
      Perioscan test) were similar in reference teeth of mother-child pairs. These data
      suggest that parents with periodontal disease may serve as a reservoir of
      periodontopathic organisms for their children.

PMID- 9590934
TI  - Titanium implants in rabbit femur: a histologic evaluation.
AB  - The success achieved by Scandinavian researchers in the development of long-term
      implants has stimulated many dentists to apply them worldwide. However, most of
      the implants did not have sufficient scientific support. The purpose of this
      study was to evaluate host tissue response to the insertion of an endosseous
      dental implant. Twenty adult New Zealand rabbits were used. Histological
      evaluation was prepared from the femurs. Results showed a hemorrhagic aspect and
      inflammatory infiltration which was subsequently substituted by granulation
      tissue, and later, formation of bone tissue. In the cortical bone, the presence
      of a necrotic area was observed which was later remodelled, and also an intense
      proliferation of endosteum and periosteum in the regions next to the implant,
      resulting in a thickening of the cortical bone surface close to the implant.
      Therefore, it was observed that titanium implants (Carbontec-Special Materials
      Ltda.) did not interfere with the bone healing process.

PMID- 9590935
TI  - Root coverage of large localized gingival recession: a biometric study.
AB  - With the objective of obtaining root coverage in areas of large localized
      gingival recessions, 16 cases of localized gingival recessions varying from 3.5
      to 10 mm (total recession) were treated with a coronally positioned gingival
      autograft in conjunction with mechanical (root planing) and chemical (saturated
      citric acid) treatment of the exposed root surfaces. Changes in sulcus depth,
      percentage of root coverage, and gain in attached gingiva were observed over the
      course of a 6-month period. The results showed no significant change in sulcus
      depth, coverage of 72.17% of the exposed root surfaces, and a gain of 3.0 +/- 1.4
      mm in attached gingiva in areas where little or no attached gingiva had existed
      prior to treatment. A positive correlation between the bone level and total
      visible recession before treatment was also demonstrated. We conclude that the
      coronally positioned gingival autograft is a highly predictable surgical
      technique for the treatment of large localized gingival recessions.

PMID- 9590936
TI  - Is there a future for private dental education in the United States?

PMID- 9590937
TI  - Billing a patient's medical insurance.

PMID- 9590938
TI  - Marketing basics: tactics for the new dentist.

PMID- 9590939
TI  - Quantitative and qualitative investigations of surface enlarged titanium and
      titanium alloy implants.
AB  - Screw shaped implants of commercially pure (c.p.) titanium and titanium-6aluminum
      4vanadium (Ti6A14V) were blasted with particles of TiO2 of mean sizes of 25
      microns (Group I) and 75 microns (Group II) and inserted in rabbit bone for 3
      months. The surface roughness of the implants was examined and quantified with an
      optical scanning 3-dimensional instrument (TopScan 3D system), revealing the two
      alloy surfaces in each group had similar surface roughness. Biomechanical
      (removal torque) tests showed the c.p. titanium implants to be significantly more
      stable in the bone bed than those of Ti6A14V. In Group I, the c.p. titanium
      implants demonstrated a mean removal torque of 38 N cm while the Ti6A14V
      demonstrated a mean removal torque of 27 N cm (P = 0.004). Group II implants
      revealed a mean removal torque of 70 N cm for the c.p. ti and 50 N cm for the
      alloy samples (P = 0.003). The removal torque values were converted to shear
      forces/strengths by three calculation methods, based on (a) the entire length of
      the implant surface in the cortical region, (b) the thickness of the cortical
      bone measured in close vicinity to the thread peaks and (c) the bone-metal
      contact length measured on the non-unscrewed neighbouring implants. Group I: (a)
      the c.p. ti implants revealed a mean shear force of 4 vs a mean of 3 N/mm2 for
      the alloy samples. Shear strengths based on (b); were 8 for c.p. ti vs 6 N/mm2
      for the alloy. The mean shear strength/force if calculated according to (c)
      revealed 23 for c.p. ti vs 18 N/mm2 for the alloy. Corresponding numbers for
      Group II; (a) c.p. ti 8 compared to 6 N/mm2 for the alloy, (b) c.p. ti
      demonstrated a mean value of 17 vs 11 N/mm2 for the alloy. According to method
      (c); c.p. ti had a mean shear strength of 26 vs 22 N/mm2 for the alloy samples.
      Histomorphometrical comparisons were performed on 10 microns thick undecalcified
      ground sections in the light microscope. In both Group I and Group II, the
      calculations of the mean bone-to-metal contact demonstrated more bone in contact
      to the c.p. titanium implants than to the Ti6A14V ones. Whereas comparisons of
      the bone volume inside the threads demonstrated slightly higher bone volumes
      around the alloy samples, no statistically significant difference was obtained
      between the two materials histomorphometrically.

PMID- 9590940
TI  - A histomorphometric evaluation of screw-shaped implants each prepared with two
      surface roughnesses.
AB  - Four different surface modifications were designed. Forty screw-shaped implants
      were divided into 4 groups, 10 screws in each. Every screw was prepared with 2
      different surface topographies. The surface topography was measured with a
      confocal laser scanning profilometer and the surface roughness was characterized
      using 1 height, 1 spatial and 1 hybrid descriptive parameter. After 12 weeks in
      rabbit bone all screws were histomorphometrically evaluated. Blasted surfaces
      demonstrated more bone in contact to implant surface compared with turned
      surfaces. Most bone in close contact to implant surface was found for a surface
      blasted with 75 microns sized particles, numerically characterized with an
      average height deviation (Sa) of 1.4 microns, an average wavelength (Scx) of 11.6
      microns and a developed surface area ratio (Sdr) of 1.5.

PMID- 9590941
TI  - Osseointegration of dental implants in bone irradiated with 40, 50 or 60 gy
      doses. An experimental study with beagle dogs.
AB  - Construction of different kinds of prostheses on irradiated bone tissues after
      tumour surgery is a complicated part of modern implantology. In irradiated
      regions of the jaws where the bone layers are thin and the blood supply also is
      minimal, knowledge of the impact of each dose of radiation is very important. The
      aim of this study was to compare the bone response around titanium implants
      loaded with fixed bridges in dog mandibles irradiated with total doses of 40, 50
      or 60 Gy. The results suggest that after irradiation with 40-50 Gy, when the dose
      is fractioned in order to achieve higher tolerance of the tissues compared with
      single dose irradiation, titanium implants may become osseointegrated in the
      mandibles. For high success rates, however, careful planning of radiotherapy and
      selection of implantation site with an adequate blood supply are essential.

PMID- 9590942
TI  - Delayed immediate implants: alveolar bone changes during the healing period.
AB  - Delaying the placement of immediate fixtures by 6-8 weeks after extraction of the
      natural dentition allows for the elimination of associated infective processes,
      the achievement of maximum osteoblastic activity that theoretically could help
      the osseointegration process and complete wound covering that simplifies the
      placement of grafts or membranes. This study examines the healing associated with
      21 fixtures in 14 patients. The fixtures were placed into sockets 6-8 weeks after
      tooth extraction without the use of barrier membranes or bone substitutes.
      Measurements were taken immediately prior to fixture placement and 3-6 months
      later at the abutment placement. Alveolar bone height, the remaining socket depth
      and diameter and the depth to which a 3.75 mm fixture could be inserted into the
      socket were measured. After fixture placement the vertical and horizontal
      measurements from the cover screw to the surrounding alveolar bone and the
      distance from the cover screw to the CEJ of the adjacent tooth were recorded. All
      fixtures were integrated at exposure with 1 failure during the follow-up period.
      The distance from the cover screw to the buccal plate decreased by a mean of 2.17
      mm. There was an increase in the mean vertical bone height at all 4 surfaces.
      When horizontal defects were present, the mean vertical distance decreased from
      2.5 +/- 0.37 mm to 0.36 +/- 0.64 mm. When horizontal defects were absent, the
      mean vertical distance decreased from 3.86 +/- 0.58 mm to 0.48 +/- 0.25 mm. There
      was also a marked decrease in the horizontal distance between the bone margin and
      the surface of the fixture from 1.6 +/- 1.73 mm to 0.02 +/- 0.02 mm. These
      results indicate a strong tendency for the defects to fill-in the horizontal
      plane and for bone growth to occur in the vertical plane to the height of the
      cover screw. In conclusion the delayed immediate placement of fixtures has a good
      short-term prognosis with bone regeneration occurring around the defect without
      the use of barrier membranes or bone substitutes.

PMID- 9590943
TI  - Evaluation of bone healing in patients with bone grafts and endosseous implants
      using single photon emission tomography (SPECT).
AB  - The aim of the present study was to evaluate the healing of onlay grafts to
      edentulous jaws in conjunction with osseointegrated implants using single photon
      emission computed tomography (SPECT). In all, 24 patients were examined who had
      received 26 full arch onlay grafts for augmentation of extremely atrophic
      edentulous jaws with secondary placement of implants 21.4 weeks after grafting.
      99m-technetium-MDP scintigrams were performed immediately after grafting, before
      implant placement, after implant placement and before abutment connection. Tracer
      accumulation was assessed semiquantitatively by calculating ratios of count
      densities between the uptake over the calvarium and over the grafted jaws based
      on 16 regions of interest in the reconstructed tomograms corresponding to 16
      possible areas of implant placement. There was a significant decrease in tracer
      uptake during graft healing, which was followed by a significant increase after
      implant placement and a subsequent decrease during implant healing. In 3
      patients, infection and partial necrosis of the grafted bone occurred. In these
      cases, tracer uptake in areas of subsequent graft infection immediately after
      grafting was significantly lower compared to patients with uneventful healing as
      a sign of inferior graft revascularization. In 3 patients, 14 implants failed due
      to mobility at the time of abutment connection or loss of osseointegration within
      the first weeks thereafter. Significantly lower levels of tracer uptake
      immediately after grafting and during graft healing were found in these areas,
      representing a lack of bone turnover due to decreased revascularization. These
      areas also showed a lower increase in tracer accumulation after implant placement
      due to the inferior graft quality, followed by a significant increase of peri
      implant bone turnover at the time of abutment connection representing
      inflammatory peri-implant bone reaction.

PMID- 9590944
TI  - An isolation and in vitro culturing method for human intraoral bone cells derived
      from dental implant preparation sites.
AB  - In dental implantology, the biocompatibility of the osseous tissue to the implant
      surface and to local environmental factors plays an important role in the process
      of healing. Bone cells derived from intraoral osseous tissue proves to be an
      important source of the osteoprogenitor cells required for healing of the
      periodontium around implants. Historically, the rat calvaria model has been
      employed to study the effects of various dental treatments on bone in vitro.
      However, there are morphological and functional differences which exist between
      bone cells derived from rat calvaria and human intraoral osseous tissue that
      impose certain limitations on the usefulness of the rat calvaria model for dental
      implant applications. Therefore, an in vitro culturing method for the isolation,
      growth and maintenance of human intraoral bone cell cultures derived from osseous
      tissues is truly warranted. In addition, a method for the accurate
      characterization of these bone cells as osteoblasts is also vital. The specific
      objective of this study was to establish isolation and in vitro culturing methods
      utilizing human intraoral bone cells derived from dental implant preparation
      sites. This paper describes techniques for the harvesting of human bone cells
      from the intraoral derived osseous tissues and discuss the procedures for
      maintaining the primary intraoral bone cell culture. In addition, our studies
      utilize established protocols for the characterization of these cells as
      osteoblasts by means of alkaline phosphatase activity determination,
      identification of cellular osteonectin and osteocalcin antigens, establishing the
      presence of cells expressing type I collagen and determining the ability of cells
      to produce calcifications. The utilization of intraoral osseous tissue may prove
      useful for future dental implant research by providing an in vitro model system
      more closely related to conditions encountered clinically.

PMID- 9590945
TI  - Complication rate with prosthodontic reconstructions on ITI and IMZ dental
      implants. Internationales Team fur Implantologie.
AB  - The aim of this study was to compare the complication rate of two implant systems
      with different prosthodontic concepts: rigid conical or resilient support of the
      suprastructure. In 66 patients, 138 ITI implants were inserted whereas 31
      patients received a total of 50 IMZ implants. Over an average observation period
      of 3.5 years (range from 0.5 to 8 years), not only was implant survival recorded,
      but also prosthodontic complications such as screw loosening, fractures of
      screws, inserts (intramobile elements, intramobile connectors) and abutments, as
      well as fractures of metal framework and veneers. With the ITI system, 28.8% of
      all devices placed exhibited such problems during the observation period. With
      the IMZ system, this rate was significantly higher (P < 0.05), in that 77.4% of
      all reconstructions required a repair at some point. The various complications
      were divided into those occurrences which affected only the suprastructure, i.e.,
      failures of frameworks, veneers, bar devices or other retentive elements, and
      those which involved implant components per se, such as screws and abutment
      components. In the first category, adverse effects occurred more frequently with
      ITI-supported prostheses (15.1%) versus IMZ suprastructures (6.4%). Regarding
      complications with implant components, the rate with IMZ components was
      considerably higher (71%) compared with ITI (13.5%). This was mainly due to the
      presence of intramobile elements (IME) and connectors (IMC) in the IMZ system. In
      this retrospective study, precise fitting, non-resilient abutment components
      leading to rigid connections of suprastructures, proved to be clinically more
      successful than resilient anchoring components.

PMID- 9590946
TI  - Histological evaluation of Bio-Oss in a 2-stage sinus floor elevation and
      implantation procedure. A human case report.
AB  - Deproteinized cancellous bovine bone (Bio-Oss) was placed as a grafting material
      for sinus floor elevation in the right posterior maxilla. After 6 months of
      healing, 3 cylindrical titanium-plasma coated implants were inserted. Six months
      later at the abutment connection, it was realized that 1 of the implants could
      not be reconstructed due to unfavorable positioning. This implant was removed
      along with a small portion of the surrounding peri-implant tissues. The specimen
      was processed according to standard techniques for hard tissue histology. In both
      the grafted area and the previously existing area of the sinus floor the bone was
      primarily of lamellar structure. Intimate contact between newly formed bone and
      the particles of the graft was present. No overt signs of resorption of the graft
      particles were visible. Histomorphometric analysis revealed 63% of implant-bone
      contact in the zone of pre-existing bone, and 73% in the grafted zone. The area
      density of bone amounted to 27% in the non-grafted as compared to 28% in the
      grafted area. In conclusion, this case report documented that deproteinized
      bovine bone, when used as a grafting material for augmentation of the sinus
      floor, may lead to proper osseointegration of a dental implant.

PMID- 9590947
TI  - A report on a new condensable composite resin.

PMID- 9590948
TI  - Crown lengthening: the periodontal-restorative connection.
AB  - Crown lengthening procedures are based on biologic principles that can be
      determinants for successful treatment. These procedures are fixed on an
      understanding of the biologic width. A few of the indications for crown
      lengthening are caries beneath the gingival margin, fractured teeth with
      insufficient clinical crown exposure, and teeth with excessive occlusal or
      incisal wear. This article describes flap designs, the use of a new bur probe for
      precise measurement of clinical crown exposure, and suturing methods for flap
      stabilization. Clinical documentation of patients with various clinical
      situations requiring crown lengthening is presented.

PMID- 9590949
TI  - Prosthodontic and surgical management of a patient with an osteoma of the
      temporomandibular joint.
AB  - Osteomas of the temporomandibular joint are rare. This article presents a case
      report delineating treatment of a partially edentulous patient using a team
      approach for an osteoma originating from the anterolateral aspect of the glenoid.
      The tumor was diagnosed with the aid of a panoramic radiograph and a computerized
      axial tomograph. Interim prostheses with anterior teeth and posterior teeth with
      nonanatomic occlusal surfaces were fabricated before surgery. After surgical
      excision of the osteoma, the interim prostheses were periodically adjusted as the
      mandibular condyle gradually shifted into the space that was previously occupied
      by the tumor. Final removable prostheses were fabricated after the condyle had
      stopped shifting.

PMID- 9590950
TI  - Direct composites in a contemporary restorative practice.
AB  - Composite resins can restore teeth to natural appearance and function while
      conserving tooth structure. Adhesive technology has revolutionized tooth
      preparation, allowing minimum tooth removal without large retentive undercuts.
      Today's dental adhesives have strong bond strengths, bonding to both dentin and
      enamel. Many are available with fewer components, simplifying application.
      Composites are available in a large variety of shades in both microhybrids and
      microfills. Microhybrids are used in areas that need strength, whereas microfills
      are used in regions that require high surface gloss or decreased stiffness.
      Composites should be placed to natural form and shades before curing; finishing
      primarily involves polishing using silicone abrasives. Composites can be used to
      restore incisal edges, close diastemas, veneer facial surfaces, and repair
      defects, making teeth appear natural.

PMID- 9590951
TI  - Saving periodontally "hopeless teeth" using calcium sulfate and demineralized
      freeze-dried bone allograft.
AB  - As the techniques of guided tissue regeneration (GTR) and implant placement
      evolve, the decision of when a tooth should be saved using GTR, or extracted and
      an implant placed, becomes much more complicated. This article discusses treating
      teeth with GTR that have traditionally had hopeless prognoses.

PMID- 9590952
TI  - All-ceramic alternatives to conventional metal-ceramic restorations.
AB  - In the search for the ultimate esthetic restorative material, many new all
      ceramic systems have been introduced to the market. One such system, In-Ceram, is
      primarily crystalline in nature, whereas all other forms of ceramics used in
      dentistry consist primarily of a glass matrix with a crystalline phase as a
      filler. In-Cream can be used to make all-ceramic crowns and fixed partial denture
      frameworks. Three forms of In-Ceram, based on alumina, spinal (a mixture of
      alumina and magnesia), or zirconia, make it possible to fabricate frameworks of
      various translucencies by using different processing techniques. This article
      discusses clinical indications and contraindications for the use of In-Ceram
      Alumina and In-Ceram Spinell all-ceramic restorations. Particular attention is
      given to cement considerations using several clinical examples.

PMID- 9590953
TI  - A new matrix in esthetic posterior restorations.
AB  - Using composite resins in posterior esthetic restorations has become more
      acceptable in recent years as a result of improvements in materials. For this
      reason, innovative products such as Luciwedge and the SuperMat System have gained
      the attention of many practitioners. SuperMat, an improved translucent matrix,
      offers a new approach to matrices for use with multimaterial fillings. It makes
      the procedure easier and offers many other advantages, particularly in composite
      compomer restorations.

PMID- 9590954
TI  - Dental implants for the facial trauma patient.

PMID- 9590955
TI  - Avoiding and coping with surgically related implant problems.

PMID- 9590956
TI  - Death rates for AIDS decrease throughout the country.

PMID- 9590957
TI  - How to sell cosmetic dentistry, Part 1: Presell.

PMID- 9590958
TI  - Choosing techniques and materials for the aesthetic practice. Interview by
      Phillip Bonner.

PMID- 9590959
TI  - Restoring severely eroded dentition with porcelain V-shaped crowns.

PMID- 9590960
TI  - Ceromers used with indirect resins/ceramics: materials, clinical applications,
      and prep guidelines.

PMID- 9590961
TI  - New concepts in air abrasion.
AB  - There is no doubt that air abrasion is going to be part of the millennial shift
      in dentistry away from traditional treatment modalities. With the change in
      incidence and morphology of caries as a result of the hardening effect of
      fluoride on enamel, this ability to remove only decayed areas and permanently
      seal the less susceptible areas becomes increasingly desirable.

PMID- 9590962
TI  - Resurgerization: sometimes the better choice.

PMID- 9590964
TI  - Nd:YAG-assisted periodontal curettage to prevent bacteria before cardiovascular
      surgery.

PMID- 9590963
TI  - Successful restorations through effective communication.

PMID- 9590965
TI  - Ridge augmentation for treatment of severe premaxillary atrophy: a surgical
      technique.

PMID- 9590966
TI  - Implant treatment planning with computerized tomography.

PMID- 9590967
TI  - Focus on the floor of the mouth.

PMID- 9590968
TI  - High-impact presentations: better outcomes with interactive patient education.

PMID- 9590969
TI  - Patient education: the profession's greatest commission.

PMID- 9590970
TI  - Effect of different types of finishing lines and etching methods of the enamel
      and dentin on the marginal integrity of Hi-ceram crowns.
AB  - Porcelain is one of the oldest materials used in the dental field. It has the
      advantages of perfect shade reproduction, chemical and abrasion resistance and
      biologic compatibility to the oral tissue. The only drawback of dental
      compatibility to the oral tissue. The only drawback of dental porcelain is the
      occurrence of brittle fracture. Minute cracks formed on the outer surface of the
      porcelain crown are the cause of the fracture. These cracks are formed during
      cooling of the ceramic as a result of low thermal conductivity of the porcelain.
      Differential dimensional changes of the outside and the internal surface take
      place inducing the cracks. Tensile stresses on the internal surface of the
      porcelain lead to cracks propagation and fracture.

PMID- 9590972
TI  - Lysosomal system of von Ebner's salivary gland in the rat.
AB  - We have examined the morphology and distribution of lysosomes in von Ebner's
      salivary gland utilizing TMPase as a marker. TMPase reactivity was detected
      basally, laterally and in the center of the cells. They include AV, Rb, MVBs and
      dense bodies. TL were detected for the first time in between the secretory
      granules and in the lateral parts of exocrine acinar cells. They were parallel to
      RER. In addition direct continuity between TL and MVBs and dense bodies was
      observed. The new locations and relations of TL supports their role in
      pinocytotic processes and cellular regularity processes.

PMID- 9590971
TI  - Diclofenac potassium in the management of dental pain: a multicenter double-blind
      comparison with glafenine.
AB  - The analgesic efficacy and tolerability of diclofenac-potassium 50 mg were
      compared with those of glafenine 200 mg in 109 outpatients suffering from
      moderate to severe dental pain. Throughout the four-day trial period, patients
      (Diclofenac-potassium: n = 58, mean age = 32.84 +/- 12.0 yrs. Glafenine n = 51,
      mean age = 34.12 +/- 14.0 yrs.) were randomised, in a double-blind fashion, to
      receive one tablet of either medications three times daily, together with an
      antibiotic, ampicillin, 500 mg, 8 hourly. Half an hour following the
      administration of the first analgesic dose, both treatment groups showed highly
      statistically significant (P < 0.001) reductions in the mean pain level when
      compared with their baseline values. The mean decrease of pain level in
      diclofenac-potassium group after 1/2 hour was significantly (P < 0.01) greater
      than that in the glafenine group. Moreover, the percent of pain free patients
      after 1/2 hour in the diclofenac-potassium group was significantly higher (P =
      0.05) compared with those in the glafenine group. The mean decreases in pain and
      tenderness on the second and fourth days, in relation to their initial values,
      were greater in the diclofenac-potassium treated patients than the glafenine
      treated ones. The overall evaluation of therapeutic effect was considered
      excellent in 72% of the diclofenac- potassium patients compared with 57% of the
      glafenine patients. Furthermore, 95% of the diclofenac-potassium patients,
      compared with 90% of the glafenine ones, expressed their willingness to use the
      trial medication again in similar conditions. None of the patients in both
      treatment groups discontinued the trial due to unwanted effects. Both therapies
      were well tolerated. Only one patient (1.72%) in the diclofenac-potassium
      treatment group experienced slight diarrhoea. It can be concluded from this study
      that both medications are effective and well tolerated in the management of
      dental pain. However, diclofenac-potassium with its fast onset of effect is
      particularly suitable in the management of acute painful conditions.

PMID- 9590973
TI  - Scanning electron microscopic study of argon laser-induced morphologic changes on
      human dental enamel and dentin.
AB  - Thirty-two human posterior teeth were used in this study to investigate the
      effect of pulsed argon laser of different densities (40, 50 and 60 J/Cm2) on the
      surface topography of human enamel and dentin. The S.E.M. results showed apparent
      alterations on the surface topography of both tissues. Increasing the energy
      density from 40 to 60 J/Cm2 showed a worse, destructive changes. Moreover, the
      effect of argon laser on dentin was more pronounced when compared with that of
      enamel irrespective of the energy density used.

PMID- 9590974
TI  - Prevalence of malocclusion in the primary and early mixed dentition in a group of
      Egyptian children with complete unilateral cleft lip and palate.
AB  - This study was carried out to investigate the prevalence of malocclusion in the
      primary and early mixed dentition for a group of Egyptian children with complete
      unilateral cleft lip and palate following surgical rep. air of the anomaly. The
      material consisted of 35 children (20 males and 15 females) with complete
      unilateral cleft lip and palate aged 3 to 7 years who were compared with 60 non
      cleft Egyptian children (37 males and 23 female) of the same age.

PMID- 9590975
TI  - Effect of reglazing and of polishing on the surface roughness of new ceramic
      restorations (Hi-ceram).
AB  - Dental porcelains are the materials from which the most esthetic and hygienic
      restorations are made. The high esthetic quality of porcelain restoration is
      attributed to its surface texture, which is characterized by reflection and
      absorption of light rays(1). Another advantage of porcelain restorations is their
      tissue biocompatibility of all the available restorative materials, the gingiva
      responds best to restorations made of porcelain(2). This is explained by the
      ability of porcelain to attain a smooth polished surface(3). Restorations with a
      smooth surface greatly impede the accumulation of plaque and thus reduce the
      incidence of gingival inflammation(4,5).

PMID- 9590976
TI  - Induction of mesenchymal neoplasms by DMBA implantation in deep lingual submucosa
      of male albino rats.
AB  - 45 male albino rats were used to study the effect of deep submucosal implantation
      of DMBA on lingual carcinogenesis. The results showed development of different
      mesenchymal neoplasms (fibroma, fibrosarcoma and leiomyosarcoma). So, this method
      of implantation could not be used as an ideal animal model for production of
      single known neoplasm as had been investigated by many investigators before.

PMID- 9590978
TI  - Prognostic value of tissue polypeptide antigen (TPA) plasma levels in patients
      with malignant salivary gland tumors.
AB  - Nine subject with various malignant salivary gland tumors were monitored with
      tissue polypeptide antigen (TPA) pre and post operatively utilizing TA radio
      immunoassay kit. The TPA radioimmunoassay proved to be a specific and sensitive
      method aiding in diagnoses monitoring and a post operative follow up in
      malignancies.

PMID- 9590977
TI  - Light and electron microscopic observations on rat molar periodontal ligament
      after intraperitoneal injection of vinblastine.
AB  - The effect of intraperitoneal injection of Vinblastine sulfate on rat periodontal
      ligament was studied. Cells still synthetize collagen after 2 hours of the
      injection with evidence of loss of extracellular collagen fibers orientation.
      Tubular lysosome could not be detected after 2 hours with formation of lysosomal
      clusters in the cell center. After 4 hours of administration, evidences of cell
      degeneration were observed. The present study has shown that Vinblastine produces
      effect on fibroblasts as early as two hours after injection.

PMID- 9590979
TI  - Uses of magnetic resonance imaging (MRI) in presurgical evaluation of internal
      derangement of temporomandibular joint (TMJ).
AB  - Nine cases of unilateral internal derangement of TMJ indicated for surgical
      intervention, were selected for this study. The affected joints were imaged by
      MRI presurgically. The non-affected joints were also imaged as controls. MRI
      findings were correlated with intraoperative surgical findings. The results were
      absolutely accurate as regards degenerative joint pathosis and capsular rupture,
      and with high degree of accuracy (85.7%) in detection of disc displacement. Two
      cases of disc perforation were not detected by MRI. The results were promising
      and encouraging the use of this noninvasive imaging technique as presurgical aid
      in TMJ disorders.

PMID- 9590980
TI  - A clinical evaluation of non-steroidal anti-inflammatory drugs (NSAIDS) as
      adjuncts in the management of periodontal disease.
AB  - Several effectors and mediators of inflammation have been identified as principle
      factors in periodontal disease progression. It has been reported that topical and
      systemic application of flurbiprofen (non-steroidal anti-inflammatory drug)
      reduced the rate of alveolar bone loss as well as signs of gingival inflammation.
      Twenty rapidly progressive as well as juvenile periodontitis patients were
      included in the present study. Results of the present study showed a significant
      reduction in pocket depth & gingival index in the experimental group over the
      control group. Radiographs revealed more bone fill in the experimental group over
      the control group.

PMID- 9590981
TI  - Scandinavian Society for the Study of Diabetes 33rd annual meeting. Elsinore,
      Denmark, 24-26 April 1998. Abstracts.

PMID- 9590982
TI  - Advice for travelers.

PMID- 9590984
TI  - The HCFA does it to labs this time. More regs, more confusion, more frustration.

PMID- 9590985
TI  - Vision after photocoagulation for diabetic retinopathy.

PMID- 9590986
TI  - Lyme disease update. Current approach to early, disseminated, and late disease.
AB  - A rational approach to diagnosis and treatment of Lyme disease requires an
      understanding of the endemic range of the tick vectors for B burgdorferi, the
      epidemiologic risk factors, and the spectrum of clinical manifestations. A two
      step approach to serologic testing (ELISA followed by Western blot analysis of
      positive or equivocal results) can be useful if the pretest likelihood of Lyme
      disease is higher than 20%. Consideration should be given to the possibility of
      (1) a noninfectious disease with clinical features similar to those of Lyme
      disease or (2) coinfection with a second tick-transmitted organism. Late Lyme
      disease must be distinguished by clinical characteristics from fibromyalgia (the
      commonest source of misdiagnosis in several studies). Antibiotic therapy should
      be tailored to the extent of disease and limited to 4 weeks in most cases. Human
      vaccines based on an outer-surface protein from B burgdorferi have been tested in
      large-scale US clinical trials and may soon be approved for use in persons whose
      occupational or recreational activities place them at risk for B burgdorferi
      exposure.

PMID- 9590987
TI  - Inflammatory bowel disease. 1. Origins, presentation, and course.
AB  - The exact cause of inflammatory bowel disease remains undiscovered, but its
      destructive nature is clearly recognized. In this article, the authors summarize
      what is known about the pathogenesis and epidemiology of ulcerative colitis and
      Crohn's disease and how to distinguish between the two, both clinically and
      pathologically. They also describe disorders that may mimic inflammatory bowel
      disease. In part 2 of this article, beginning on page 86, the authors discuss
      some of the therapeutic options that are the commonly used as well as some that
      are investigational but show promise for patients with this chronic and relapsing
      disease.

PMID- 9590988
TI  - Inflammatory bowel disease. 2. Current and future therapeutic options.
AB  - The exact source of interference with the normal protective immune response in
      patients with inflammatory bowel disease remains unclear. Infectious causes have
      been proposed, and the increased incidence among family members indicates genetic
      predisposition. No matter what the pathogenesis may be, the disease is chronic,
      recurrent, and destructive in many cases. Conventional therapy with 5-ASAs,
      corticosteroids, immunomodulating agents, methotrexate, and antibiotics often
      offers relief. However, adverse effects accompany long-term use of many of these
      agents, so follow-up is important. Much investigation of alternative methods is
      under way, and anecdotal as well as published experience suggests benefits in at
      least some patients. Because of the chronic nature of their condition, patients
      with inflammatory bowel disease often become quite sophisticated in their
      understanding of treatment methods. Therefore, they should be told of updates
      regarding new options for disease control. We recommend that patients be seen
      periodically by a gastroenterologist who has expertise in inflammatory bowel
      disease, even when the disease is quiescent. Our experience in observing these
      patients over time strongly supports use of some of the agents discussed in this
      article for prophylaxis against flares and chronic inflammation.

PMID- 9590989
TI  - The saga of the sore on the shin.

PMID- 9590990
TI  - Cataracts. Lifting the clouds on an age-old problem.
AB  - Cataracts are the most common treatable form of reduced vision in older adults.
      Although the incidence of cataracts is high after age 65, careful history taking
      and clinical examination are essential to establish the diagnosis. Cataract
      surgery is medically indicated when the view to the retina is obscured or lens
      induced disorders place the eye at risk for further damage. However, even when
      patients have no specific associated medical problem, other than decreased visual
      acuity, cataract extraction offers an important means for maintaining
      independence and improving quality of life.

PMID- 9590991
TI  - Exposing glaucoma. Primary care physicians are instrumental in early detection.
AB  - Glaucoma is a common, insidious cause of blindness in the general population,
      especially in older patients. Although much is still unknown about the symptoms
      and pathogenesis of this group of ocular diseases, primary care physicians can
      make a major difference in reducing vision loss by identifying high-risk patients
      at an early stage of disease. A history that assesses important risk factors and
      a physical examination that includes the flashlight test and close inspection of
      the optic nerve for color of neuroretinal rim and cupping improve the chances of
      early diagnosis and treatment of glaucoma.

PMID- 9590992
TI  - Age-related macular degeneration. Can we stem this worldwide public health
      crisis?
AB  - Age-related macular degeneration, the leading cause of legal blindness in people
      over age 60 worldwide, represents a public health crisis that deserves the
      attention and understanding of all physicians. The dry form of the disease is
      more common than the wet, but the wet form causes the most severe vision loss.
      Other than vision aids (e.g., glasses, magnifiers), no treatments or preventive
      measures are currently available for patients with dry macular degeneration, and
      laser photocoagulation with fluorescein angiography is the only clinically proven
      therapy for neovascular disease. Indocyanine green angiography is a promising new
      imaging tool that may improve detection of patients likely to benefit from laser
      therapy. Until better diagnostic and treatment options are available, early
      screening and patient education offer the best hope for reducing the widespread
      devastation caused by this disease.

PMID- 9590993
TI  - Living with low vision. What you can do to help patients cope.
AB  - Patients with irreversible vision loss are understandably distressed, but
      physicians can help guide them to successful independent living. In this
      practical article, Dr Faye discusses the causes of low vision, offers tips for
      working with visually impaired patients in the office setting, and describes
      rehabilitation programs for such patients. A list of resources on low vision is
      also included.

PMID- 9590994
TI  - Office management of posttraumatic stress disorder. A clinician's guide to a
      pervasive problem.
AB  - Primary care physicians are often called on to help patients and families
      struggling with posttraumatic stress disorders. The characteristic clusters of
      symptoms, namely, reexperiencing, avoidance, and hyperarousal, are easily
      confused with other disorders, particularly since symptoms can occur months or
      even years after the initial trauma. Treatment includes drug therapy and clinical
      office techniques to stabilize symptoms, such as interrupting traumatic
      flashbacks, educating family members about effective home care, and redirecting
      unhealthy self-blame and aggression. Nonetheless, some patients need psychiatric
      referral for further processing of traumatic perceptions and adaptive integration
      of the trauma into a self-view and world-view.

PMID- 9590995
TI  - Irritant contact dermatitis. Clues to causes, clinical characteristics, and
      control.
AB  - Skin irritation can cause poorly defined nonimmunologic cutaneous changes that
      may cause diagnostic confusion. Clinical signs include vesicles, papules, bullae,
      erythema, edema, scaling, and lichenification. In some patients, this condition,
      termed irritant contact dermatitis, is indistinguishable from endogenous,
      dyshidrotic, nummular, and atopic dermatitis. Irritant contact dermatitis has
      only a few typical characteristics. The diagnosis is generally based on clinical
      appearance, history and, when indicated, diagnostic patch testing to rule out an
      allergic component. Elimination of the offending agent and protection from
      further exposure are important in both diagnosis and management. The dermatitis
      usually heals once the irritant is eliminated, and reexposure should be minimized
      for weeks to months, if not permanently.

PMID- 9590996
TI  - Outpatient management of HIV-infected adults. The varied challenges for primary
      care.
AB  - Care of persons infected with HIV presents many challenges to primary care
      physicians. In addition to keeping current on the rapidly advancing medical
      aspects of the disease, physicians also must be prepared to recognize the complex
      psychosocial issues that confront their patients. In this article, Dr Myers
      reviews essential aspects of primary care for HIV-infected adults.

PMID- 9590997
TI  - Preventive foot care. A user-friendly system for patients and physicians.
AB  - Our user-friendly foot skin and toenail grading system is simple to understand
      for both patients and physicians. Current medical practice dictates that primary
      care physicians deliver the most comprehensive care possible for their patients.
      This includes preventive care and documentation of outcomes. Our approach
      simplifies evaluation and management of the majority of foot skin and toenail
      conditions in compromised hosts. Reimbursement for the extra care is justified,
      and authorized billing codes exist. Our system helps to prevent the physical,
      emotional, and financial costs associated with severe foot wounds and nail
      disorders. We remind our patients that proper foot care is as important in
      preventing foot complications as drug therapy is in preventing complications in
      other organs. Our approach to foot skin and toenail care is largely prophylactic
      and can be easily instituted in a primary care practice.

PMID- 9590998
TI  - Testosterone replacement therapy. What is its potential in elderly men?
AB  - Currently, the use of testosterone replacement therapy in elderly men is not
      considered routine. However, the aging population makes it an increasingly
      important issue for primary care physicians, and therapy can be effectively
      managed in a primary care setting when indicated. Because of testosterone's
      potential side effects, therapy should be customized and patients must be
      carefully monitored. This treatment has tremendous potential, but further
      research is needed before routinely recommending it for hypogonadal elderly men.

PMID- 9590999
TI  - The erythrocyte sedimentation rate. Still a helpful test when used judiciously.
AB  - ESR is a time-honored, simple, inexpensive test, but unfortunately it lacks
      sensitivity and specificity. Clinicians need to be aware of appropriate uses,
      because any test is expensive when ordered often, and evaluation of false
      positive results may incur substantial costs and place the patient at risk from
      additional procedures. ESR should not be used to screen asymptomatic persons for
      disease. If an increased ESR is encountered and no explanation is immediately
      apparent, clinicians should repeat the test in several months rather than pursue
      an exhaustive search for occult disease. ESR may be useful in establishing a
      "sickness index" in elderly persons who have nonspecific changes in health status
      and a moderate probability of underlying disease; in screening for infection in
      specific settings (e.g., orthopedic surgery, pediatrics, gynecology); in
      diagnosing and monitoring temporal arteritis, polymyalgia rheumatica, and
      possibly other rheumatic diseases; in monitoring patients with treated Hodgkin's
      disease; and in assessing iron deficiency in anemia of chronic disease (when
      correlated with serum ferritin level). An ESR value exceeding 100 mm/hr has a 90%
      predictive value for serious underlying disease, most often infection, collagen
      vascular disease, or metastatic tumor. In asymptomatic persons with a markedly
      elevated ESR value, a minimal number of tests usually reveal the cause.

PMID- 9591000
TI  - A randomized, prospective, blinded comparison of postoperative pain, metabolic
      response, and perceived health after laparoscopic and small incision
      cholecystectomy.
AB  - BACKGROUND: We have previously shown that in a randomized comparison of
      laparoscopic (LC) versus small incision (SC) cholecystectomy, postoperative
      hospital stay is comparable. This randomized prospective study compares the
      postoperative pain, analgesic and antiemetic consumption, perceived health, and
      metabolic and respiratory responses after these two procedures. METHODS: Two
      hundred patients were recruited; postoperative stay, pain scores, analgesic and
      antiemetic consumption were recorded. Nottingham Health Profile questionnaires
      were completed by a subgroup of 100 patients, and the metabolic and respiratory
      responses were also compared in a further subgroup of 20 patients. RESULTS: Pain
      scores in both groups were low. LC, however, was associated with lower
      postoperative pain scores and analgesic requirements compared with SC, but the
      antiemetic requirements were greater after LC. The duration of hospital stay and
      the perceived health after operation were the same in both groups, and both
      procedures were associated with a similar reduction of respiratory function.
      Twenty-four hours after operation the inflammatory (C-reactive protein, CRP)
      response to LC (22 +/- 20 mg/L) was significantly lower than after SC (68 +/- 30
      mg/L), but the neuroendocrine (cortisol) response was similar (LC, 475 +/- 335
      nmol/L, compared with SC, 710 +/- 410 nmol/L). Independent of the technique used,
      the duration of postoperative hospital stay correlated significantly with the
      magnitude of both the 24-hour postoperative cortisol and CRP responses (cortisol:
      rs = 0.678, p < 0.001; CRP: rs = 0.566, p = 0.011). CONCLUSIONS: LC appears to be
      associated with less tissue destruction and pain than SC, but this did not confer
      any advantage in the degree of postoperative respiratory impairment, length of
      hospital stay, or postoperative perceived health. The neuroendocrine component of
      the metabolic response evoked by each procedure was similar and had a significant
      correlation to patient's postoperative hospital stay. This finding may explain
      the similar postoperative recovery after LC and SC.

PMID- 9591001
TI  - The readability of currently used surgical/procedure consent forms in the United
      States.
AB  - BACKGROUND: Informed consent forms are universally used by hospitals throughout
      the United States before surgery or invasive procedures. This survey was
      undertaken to determine the content of these forms and their ability to be
      understood by individuals with differing reading comprehension levels. METHODS:
      Ten percent of all U.S. hospitals were requested to forward a copy of their
      current surgical/procedural informed consent form. The forms received were
      digitized and computer assessed for readability. In addition, each form was
      evaluated for a variety of items with respect to content. RESULTS: Of the 2194
      requests mailed, 681 responses were received including 616 with
      surgical/procedural consent forms. The mean grade level required to understand
      these consent forms was 12.6 (+/- 3.1). There was no variability in readability
      scores on the basis of hospital bed size. Of the 616 consent forms reviewed, 29,
      146, 347, and 461 forms could be understood by individuals reading at a grade
      level of less than 8 and at least 8, 10, and 12 years of education, respectively.
      Although most required the name of the patient, physician, and procedure, the
      majority did not describe or provide a full-in blank for the specific benefits,
      risks, and alternatives to the procedure. CONCLUSIONS: The majority of
      surgical/procedural informed consent forms currently used by U.S. hospitals are
      complex and are not easily understood by the average patient. In addition, the
      majority of reviewed consent forms do not list specific benefits or potential
      complications of the planned surgery/procedure.

PMID- 9591002
TI  - Hyperamylasemia after cardiopulmonary bypass: pancreatic cellular injury or
      impaired renal excretion of amylase?
AB  - BACKGROUND: Postoperative hyperamylasemia and even acute pancreatitis are
      associated with coronary artery bypass grafting (CABG). The mechanism of
      hyperamylasemia and pancreatic acinar cell damage was studied in 20 patients
      undergoing CABG. METHODS: Serial blood and urine samples at eight time points
      before, during, and 24 hours after the CABG were collected. Salivary and
      pancreatic isoamylases, the fractional clearance of isoamylases (i.e., relative
      to creatinine clearance), pancreatic phospholipase A2 (a specific serum marker of
      pancreatic acinar cell injury), and cystatin C (a sensitive marker of glomerular
      filtration rate) were measured. RESULTS: Mild serum hyperamylasemia (300 to 1000
      units/L) was found in 11 of 20 (55%) and severe (> 1000 units/L) in 6 of 20 (30%)
      patients with no signs of clinical acute pancreatitis. Hyperamylasemia occurred
      from 6 to 24 hours after the CABG and was mainly caused by pancreatic isoamylase.
      Serum pancreatic phospholipase A2 concentration remained unchanged, which
      excludes acinar cell damage. Although renal glomerular filtration was normal
      during CABG as measured by serum cystatin C and creatinine clearance, the
      fractional clearance of isoamylases decreased. CONCLUSIONS: The decreased rate of
      excretion into urine, rather than pancreatic cellular damage, is the major source
      of hyperamylasemia after CABG.

PMID- 9591003
TI  - The effects of programmatic change on resident motivation.
AB  - BACKGROUND: Critical to any resident's success is that individual's commitment
      and desire to succeed. Rarely do surgical educators consider the impact of a
      programmatic change on a resident's motivation. Recently much attention has
      centered around the impact of IL-372 on medical practice. In this article we
      instead focus on the impact that a programmatic change can have on resident
      motivation and use IL-372 as an example. METHODS: This article is a review of
      literature on motivation relevant to surgical education. RESULTS: Motivation
      theory can help surgical educators understand resident (1) choice to engage in an
      activity, (2) the quantity of effort someone invests, and (3) the willingness to
      persist at tasks. It can also help educators identify and understand positive and
      negative behavioral reactions that can occur when there is a mismatch between a
      resident's belief about his or her ability and expectations in the operating
      room. CONCLUSIONS: This article concludes with a number of strategies to improve
      resident motivation.

PMID- 9591004
TI  - Calcitonin gene-related peptide and spinal afferents partly mediate postoperative
      colonic ileus in the rat.
AB  - BACKGROUND: Calcitonin gene-related peptide (CGRP) is a widely distributed
      neuropeptide contained in intrinsic and extrinsic neurons of the gastrointestinal
      wall that has been shown to be released by noxious stimulation, to be involved in
      nociception, to inhibit gastrointestinal motility, and to partly mediate
      postoperative gastric ileus. We hypothesized that abdominal surgery-induced
      release of CGRP might inhibit postoperative colonic motility and food intake.
      METHODS: Colonic transit, stool pellet number, stool pellet weight, and food
      intake were measured for 48 hours after induction of postoperative ileus in rats.
      CGRP was immunoneutralized by preoperative injection of CGRP monoclonal antibody,
      or visceral afferent nerve fibers containing CGRP were functionally ablated by
      topical capsaicin treatment of the vagus nerves or of the celiac/superior
      mesenteric ganglia before abdominal surgery. RESULTS: Abdominal surgery increased
      colonic transit time and decreased 24-hour cumulative stool pellet number, stool
      pellet weight, and food intake. CGRP immunoneutralization reversed postoperative
      inhibition of colonic transit, 24-hour cumulative stool pellet number, stool
      pellet weight, and food intake by 77%, 82%, 80%, and 52%, respectively. Whereas
      ablation of vagal afferent nerve fibers had no effect, spinal afferent nerve
      fiber ablation reversed postoperative inhibition of 24-hour cumulative stool
      pellet number, stool pellet weight, and food intake by 41%, 38%, and 19%,
      respectively. CONCLUSIONS: CGRP and spinal afferent nerve fibers partly mediate
      postoperative colonic ileus and inhibition of food intake in the rat. By the
      magnitude of reversal of postoperative ileus, CGRP seems to be an important
      mediator of postoperative colonic ileus. Our results for the first time show
      involvement of a neuropeptide and spinal afferents in the mediation of
      postoperative colonic ileus and postoperative inhibition of food intake in rats.

PMID- 9591005
TI  - Systemic and splanchnic metabolic response to exogenous human growth hormone.
AB  - BACKGROUND: Evidence exists indicating that growth hormone (GH) resistance in
      some disease states such as hypercatabolic conditions may limit the metabolic
      benefit associated with recombinant human growth hormone (rhGH) administration.
      It was the purpose of this study to compare the systemic and splanchnic effects
      of rhGH in patients with sepsis exhibiting systemic inflammatory response
      syndrome (SIRS) with the response observed in normal volunteers. Because insulin
      like growth factor I (IGF-I) is believed to be the dominant factor responsible
      for the anabolic effects of rhGH, particular attention was given to this
      secondary effector. METHODS: The systemic and splanchnic effects of rhGH (0.15
      mg/kg/day) were studied in normal volunteers (n = 5), critically ill patients
      with sepsis exhibiting SIRS (n = 6), and patients with sepsis exhibiting SIRS
      while receiving total parenteral nutrition (n = 6). Basal and end study IGF-I,
      urinary urea excretion, hepatic blood flow, hepatic venous oxygen content, and
      splanchnic oxygen exchange were measured after a 48-hour course of rhGH. RESULTS:
      Fasting basal IGF-I concentrations were reduced by 75% to 83% in patients with
      sepsis/SIRS relative to normal control subjects. After 48 hours of rhGH, peak IGF
      I concentrations were 74% and 76% lower in patients in the Sepsis/SIRS and
      Sepsis/SIRS + Nutrition groups, respectively, compared with normal control
      subjects. Despite the attenuated IGF-I rise in patients, urea excretion declined
      by a similar magnitude in all three groups. Hepatic blood flow remained
      unaffected, but rhGH administration increased splanchnic oxygen consumption in
      all groups (control, +57%*; Sepsis/SIRS, +13%; Sepsis/SIRS + Nutr +42%*; *p <
      0.05 relative to corresponding basal) resulting in a decline of basal to end
      therapy hepatic venous oxygen saturation (control, 67 +/- 4% to 62 +/- 11%;
      Sepsis/SIRS, 51% +/- 14% to 43% +/- 14%*; Sepsis/SIRS + Nutr, 62% +/- 11% to 55%
      +/- 16%; *p < 0.05 relative to corresponding control value), suggesting that rhGH
      may induce centrilobular hepatic hypoxia, which may contribute to the diminished
      IGF-I response. CONCLUSIONS: Although critically ill patients exhibit an IGF-I
      increase in response to exogenous rhGH, the rise is markedly attenuated compared
      with healthy volunteers, indicating the presence of GH resistance. Unexpectedly,
      the changes in the anabolic hormone IGF-I did not appear to be related to the
      reduction in urea excretion. This may provide some additional evidence for IGF-I
      resistance. Finally, rhGH is associated with an augmented splanchnic oxygen
      consumption but no corresponding increase in regional blood flow. As a result,
      regional tissue hypoxia may arise and contribute to the impaired or suboptimal
      IGF-I response pattern.

PMID- 9591006
TI  - Depression of peritoneal fibrinolysis during operation is a local response to
      trauma.
AB  - BACKGROUND: Peritoneal fibrinolytic capacity decreases during abdominal
      operation. This may be a local effect or a part of a generalized response to the
      procedure. METHODS: Plasma and paired peritoneal biopsy specimens were taken at
      intervals during abdominal operation, and fibrinolytic components were assayed in
      plasma and tissue extracts. Values are given as median [interquartile range].
      RESULTS: In peritoneal tissue there was a gradual decrease of tissue-type
      plasminogen activator (tPA) activity, and at 90 minutes of the operation differed
      significantly from that of the initial sample (1.0 [1.0] ng/mg protein, and 5.1
      [6.5] ng/mg protein, respectively, p < 0.05). The tPA activity levels at the
      wound were significantly lower (1.0 [1.0] ng/mg protein) at 90 minutes compared
      with a remote peritoneal site (1.8 [1.9] ng/mg protein, p < 0.05). At the wound,
      the tPA activity correlated significantly with time (r = -0.48, n = 26, p <
      0.01). tPA activity and antigen peaked in plasma at 30 minutes (p < 0.05) and 60
      minutes (p < 0.05), respectively. Plasminogen activator inhibitor type 1 activity
      increased in plasma during operation (p < 0.05), but was not detectable in
      peritoneal samples. CONCLUSIONS: The intraoperative changes in tissue tPA
      activity were not consistently reflected in plasma samples. These findings
      suggest that the reduction in peritoneal fibrinolysis during abdominal operation
      is a local response to trauma.

PMID- 9591007
TI  - Advantage of preoperative portal vein occlusion for hepatectomy that exceeds
      portal vein occluded lobes.
AB  - BACKGROUND: The purpose of our study was to examine the effect of preoperative
      portal vein (PV) occlusion on hepatic reserve function after extended hepatectomy
      that is an excision of areas beyond the PV occluded lobes. METHODS: Male Wistar
      rats were divided into three groups and underwent a two-stage operation: a PVL
      hepatectomy group (ligation of the PV [PVL] of the left and median lobes followed
      by hepatectomy of the right lobes together with the PV occluded lobes), a sham
      88% hepatectomy group (sham operation without PVL followed by hepatectomy
      corresponding to the lobes excised in the PVL-hepatectomy group), and a sham-67%
      hepatectomy group (sham operation followed by hepatectomy of the left and median
      lobes to approximate the volume excised in the PVL-hepatectomy group). In all
      subjects, hepatectomy was carried out 7 days after the PVL or sham operation. On
      days 0, 1, 2, and 3 after hepatectomy, liver weight, histologic elements, DNA
      synthesis rates, energy charge, adenine nucleotides, and lipoperoxide levels of
      the remaining liver were determined. RESULTS: In the sham-88% hepatectomy group,
      the volume of resected liver was 88.2% +/- 0.5%. In the PVL-hepatectomy group it
      was 69.1% +/- 0.8%, although anatomically identical lobes were excised. At the
      time of hepatectomy, DNA synthesis, hepatic concentrations of adenine nucleotides
      and lipoperoxide, and serum liver function tests showed similar results in all
      three groups. The survival rate 3 days after hepatectomy was significantly low
      (53%) in the sham-88% hepatectomy group, whereas it was 100% in the PVL
      hepatectomy and sham-67% hepatectomy groups. The gain in liver weight per day was
      significantly lower in the sham-88% hepatectomy group than in the other two
      groups. The decline in hepatic energy charge after hepatectomy was less, with
      less activated DNA synthesis, in the PVL-hepatectomy group compared with the sham
      88% hepatectomy and sham-67% hepatectomy groups. Lipoperoxide concentration in
      the PVL-hepatectomy group was significantly lower than that in the sham-88%
      hepatectomy and sham-67% hepatectomy groups. CONCLUSIONS: Preoperative PV
      occlusion not only increases the remaining liver volume but also is advantageous
      to hepatic reserve after hepatectomy that exceeds PV occluded lobes.

PMID- 9591008
TI  - Surgical results in patients with dual hepatitis B- and C-related hepatocellular
      carcinoma compared with hepatitis B- or C-related hepatocellular carcinoma.
AB  - BACKGROUND: The purpose of our study was to report on the surgical outcomes of
      patients with hepatocellular carcinoma (HCC) with dual hepatitis B virus (HBV)
      and hepatitis C virus (HCV) infections and to assess the differences in the
      surgical results between those patients and the patients with hepatitis B- or
      hepatitis C-related HCC. METHODS: The operative outcomes of 13 patients with
      hepatitis B surface antigen (HBsAg)-positive and hepatitis C antibody (HCV Ab)
      positive (the BC-HCC group) results, 57 patients with HBsAg-positive and HCV Ab
      negative (the B-HCC group) results, and 34 patients with HBsAg-negative and HCV
      Ab-positive (the C-HCC group) results, who had undergone hepatic resection from
      1991 to 1995, were compared. RESULTS: The operative mortality rate within 1 month
      after operation for patients with BC-HCC was 7.7%. No statistically significant
      difference was found compared with the patients with B-HCC and C-HCC (5.3% and
      5.9%, respectively). The postoperative course of patients with BC-HCC was
      complicated by liver failure, postoperative ascites, and wound infection in one
      patient each. Also, no statistically significant difference was found among the
      groups (23.1%, 22.8%, and 20.5% for patients with BC-HCC, B-HCC, and C-HCC,
      respectively). The overall 1-, 3-, and 5-year survival rates of patients with BC
      HCC in this series were 75%, 50%, and 40%, respectively. The postoperative
      recurrence rate was 66.7%. No statistically significant differences were found
      between the various groups of the virus-related HCC on the overall survival rate
      and disease-free survival rate. CONCLUSIONS: Hepatic resection for HCC in
      patients with dual HBV and HCV infections was associated with slightly higher
      operative morbidity and mortality rates, but there were no statistical
      differences compared with hepatitis B- or C-related HCC regarding the survival
      and recurrence rates.

PMID- 9591009
TI  - Euthyroid sick syndrome, associated endocrine abnormalities, and outcome in
      elderly patients undergoing emergency operation.
AB  - BACKGROUND: Emergency operation in the elderly carries a high risk of death. We
      investigated the incidence of euthyroid sick syndrome (ESS) and associated
      nutritional and endocrine abnormalities and their relationship to postoperative
      outcome in this population. METHODS: Sixty-six patients older than 70 years of
      age requiring emergency operations were assessed before any therapeutic
      intervention. Values for thyroid hormones, catecholamines, cortisol, interleukin
      6, interleukin-1, C-reactive protein, and the Acute Physiology and Chronic Health
      Evaluation II score were determined. Nutritional assessment was carried out.
      Mortality rates and duration of hospital stay were related to ESS and albumin
      concentrations. RESULTS: ESS was diagnosed in 34 patients (51.50%) and was
      associated with worse Acute Physiology and Chronic Health Evaluation II scores
      (10.9 vs 8.6; p = 0.004), hypoalbuminemia (34.7 vs 40.8 gm/L; p = 0.0001), lower
      triceps skinfold (11.8 vs 14.6 mm; p = 0.03), and higher cortisol and
      norepinephrine levels (937 vs 741 nmol/L [p = 0.04] and 358 vs 250 pg/ml [p =
      0.02], respectively), interleukin-6 plasma concentrations (347 vs 113 pg/ml; p =
      0.01), death rate (20% vs 0%; p = 0.02), and length of hospital stay (17.2 vs
      11.8 days; p = 0.03). A serum albumin level less than 35 gm/L was virtually
      always associated with ESS. CONCLUSIONS: ESS is highly prevalent in the elderly
      with acute surgical problems and is associated with poor nutrition, higher
      sympathetic response, and worse postoperative outcome. The serum albumin level at
      admission is a specific marker of ESS.

PMID- 9591010
TI  - Diarrhea after resection of advanced abdominal neuroblastoma: a common management
      problem.
AB  - BACKGROUND: After resection of advanced abdominal neuroblastoma, children may
      have persistent postoperative diarrhea. Until recently, the magnitude of this
      problem had not been appreciated. METHODS: To assess the incidence, severity, and
      management of chronic postoperative diarrhea in these patients, we reviewed the
      case notes of all children with stage III or IV abdominal and pelvic
      neuroblastoma who underwent tumor resection in our hospital between January 1985
      and September 1996. We classified the severity of diarrhea as follows: mild, less
      than 3 loose stools per day; moderate, 3 to 5 loose stools per day; and severe,
      more than 5 loose stools per day and/or urgency, incontinence, or nocturnal
      diarrhea. RESULTS: Seventy-seven children underwent resection during this period,
      and 23 (30%) had postoperative diarrhea, classified as mild in 11 patients,
      moderate in 7, and severe in 5. Dissection around the superior mesenteric and
      celiac arteries was associated with a significantly higher incidence of diarrhea.
      Fifteen children (65%) received treatment with loperamide, which reduced but did
      not abolish symptoms. Twelve children subsequently died of progressive
      neuroblastoma. Of the 11 surviving children (mean duration of follow-up, 8.4
      years), 8 have persistent loose stools. CONCLUSIONS: Diarrhea, probably resulting
      from disruption of the autonomic nerve supply to the gut during clearance of
      tumor from the major vessels of the retroperitoneum, is common after resection of
      advanced abdominal neuroblastoma. Many children require long-term treatment to
      slow intestinal peristalsis, and a few have severe and unremitting diarrhea. More
      effective medical management of this complication is needed.

PMID- 9591011
TI  - Evidence of survival benefit of extended (D2) lymphadenectomy in western patients
      with gastric cancer based on a new concept: a prospective long-term follow-up
      study.
AB  - BACKGROUND: The use of extended (D2) lymph node dissection in gastric cancer
      achieves better locoregional tumor control than limited (D1) lymphadenectomy, but
      its influence on survival is controversial. The value of D2 resection is unproven
      in randomized trials. However, a survival benefit in favor of D2 resection has
      been shown in reports from some specialized centers. This study was undertaken to
      assess whether D2 resection improves survival. We evaluated the efficacy of D2
      resection on the basis of a new concept that eliminates the stage migration
      phenomenon. METHODS: D2 resection achieved with a standardized technique in this
      prospective study included dissection of the perigastric lymph nodes (stations 1
      through 6, D1 resection), as well as those at the celiac axis (stations 7 through
      11) and at hepatoduodenal ligament (station 12, N2 level). We evaluated survival
      data of patients with involved nodes at stations 7 through 12 (N2 disease)
      because these nodes are left behind in a D1 resection. RESULTS: D2 resection
      resulted in a resection of cure in 31 patients with N2 disease, a 25% (31 of 125)
      increase of the curative resection compared with a supposed D1 resection. The 5
      year survival rate for N2 patients was 17%, which demonstrates the therapeutic
      benefit of the D2 resection. In patients with pN0 and pN1 disease, the 5-year
      survival rates were 71% and 53%, respectively. Overall hospital mortality and
      morbidity were 1.3% (2 of 146) and 33.4% (40 of 146), respectively. CONCLUSIONS:
      D2 resection can be performed safely and is of therapeutic value in patients with
      advanced lymph node metastases. Furthermore, the survival data suggest indirectly
      a possible beneficial effect for patients with node-negative disease (N0) or
      early node metastases (N1).

PMID- 9591013
TI  - Successful treatment of delayed splenic rupture with splenic artery embolization.

PMID- 9591012
TI  - Wound metastasis after laparoscopy with different insufflation gases.
AB  - BACKGROUND: There is growing evidence that laparoscopy for malignancy is
      associated with an increased incidence of metastasis to port sites. This study
      investigated the effect of different insufflation gases on port-site metastasis
      after laparoscopy in an established animal model. METHODS: Forty-eight Dark
      Agouti rats with an established adenocarcinoma in the left flank underwent
      laparoscopic intraperitoneal tumor laceration. The gas used for insufflation was
      one of the following (12 rats in each group): (1) CO2, (2) N2O, (3) helium, or
      (4) air. Rats were killed 7 days after the procedure, and the port sites were
      examined for the presence of tumor metastasis. RESULTS: Tumor involvement of port
      sites was significantly less likely after helium insufflation than in the other
      groups (p < 0.0001). There was no significant difference between the air, CO2,
      and N2O groups. CONCLUSIONS: This study suggests that the development of
      metastases in port sites after laparoscopy may be influenced in part by the
      choice of insufflation gas used to create the pneumoperitoneum. In particular,
      helium was associated with a reduced rate of metastases.

PMID- 9591014
TI  - A false-positive diagnosis of C-cell hyperplasia in a member of a family with
      multiple endocrine neoplasia type 2A and familial colonic polyposis.

PMID- 9591015
TI  - Pleural effusion as the presentation for primary effusion lymphoma.

PMID- 9591016
TI  - Gangrene of the back, buttocks, fingers, and toes caused by transient cold
      agglutinemia induced by a cooling blanket in a patient with sepsis.

PMID- 9591018
TI  - Effect of transfusion on physiologic changes after resuscitation.

PMID- 9591017
TI  - Intrahepatic splenic tissue in a patient with recurrent idiopathic
      thrombocytopenic purpura.

PMID- 9591019
TI  - Historical perspective of lymphatic tumour spread and the emergence of the
      sentinel node concept.

PMID- 9591020
TI  - Technique of sentinel node resection in melanoma and breast cancer: probe-guided
      surgery and lymphatic mapping.

PMID- 9591021
TI  - Consequences of sentinel node in clinical decision making in breast cancer and
      prospects for future studies.

PMID- 9591022
TI  - European guidelines for quality assurance in the surgical management of
      mammographically detected lesions.

PMID- 9591023
TI  - The National Health Service Breast Screening Programme in the Trent region--are
      we meeting the targets?

PMID- 9591024
TI  - Prognostic role of lymph-node level involvement in patients undergoing axillary
      dissection for breast cancer.
AB  - AIMS: Clinical records of patients undergoing surgery for breast cancer were
      reviewed in order to evaluate the prognostic role of lymph-node level
      involvement. METHODS: From 1982 to 1991, 1143 patients had radical mastectomy or
      conservative surgery with total axillary dissection: 461 patients of mean age
      57.1 years (range: 25-89 years) were lymph-node positive (pN1); 369 patients
      (80%) had radical mastectomy; and 92 patients (20%) had conservative treatment
      plus post-operative radiotherapy, with the same mean number (n = 16) of lymph
      nodes collected in the surgical specimen. Data were analysed for the number of
      positive lymph nodes and level of involvement. RESULTS: Level I, Levels I + II
      and Levels I + II + III were involved in 44.9, 18 and 21.4% of patients,
      respectively; 'skip metastases' occurred in 72 of 461 pN1 patients (15.5%). A
      univariate analysis showed that prognosis was directly related to the number of
      levels involved (P < 0.001), and skip metastases had the same prognostic role as
      Level I involvement. The numbers of involved lymph-node levels and metastatic
      lymph nodes were well correlated; multivariate analysis showed that involvement
      of Levels I and III was independently correlated with prognosis. After adjustment
      for age and number of positive lymph nodes, the number of involved lymph-node
      levels was an independent prognostic factor, with highest predictability when all
      three lymph-node levels were positive (P = 0.009). CONCLUSIONS: The prognostic
      value of lymph-node status should be defined not only by the number of metastatic
      lymph nodes, but also by the number of levels of involvement.

PMID- 9591025
TI  - The significance of involved tumour bed biopsy following wide local excision of
      breast cancer.
AB  - AIM: Following wide local excision of breast cancer approximately 25% of patients
      have residual disease in the tumour bed. The aim of this study was to determine
      whether positive bed biopsy correlated with either local recurrence or overall
      survival. METHOD: Following wide excision bed biopsies were taken at four
      separate sites from the tumour bed. Histopathological assessment of the bed
      biopsies was made and compared to features within the primary tumour. Patients
      were followed-up over a median period of 6.17 years and local recurrence and
      survival data documented. RESULTS: Two hundred and sixty-eight patients were
      included in the study and 63 had positive bed biopsies. In all, 85 patients had a
      recurrence of breast cancer and 69 died. Kaplan-Meier plots showed no evidence of
      a difference in survival between bed biopsy positive and negative patients. Bed
      biopsy positive patients were at greater risk of local recurrence. CONCLUSIONS:
      These findings suggest that positive bed biopsy is associated with an increase in
      local recurrence rates but has no effect on overall survival following wide
      excision of breast cancer.

PMID- 9591026
TI  - Synovial sarcoma: oncological and functional results.
AB  - AIM: To evaluate the oncological and functional result of the treatment of
      patients with a synovial sarcoma. This paper gives a retrospective review of 20
      patients (15 male and five female) treated for synovial sarcoma at the Nijmegen
      University Hospital, The Netherlands. METHODS: The median age of the patients was
      30 years (range: 14-71, mean 37 years). RESULTS: The tumour locations were: lower
      extremity in 12 patients; upper extremity in three; pelvic and groin region in
      four; and the retroperitoneal space in one. Surgical stages according to Enneking
      (Clin Orthop 1986; 204: 9-24) were IIA in five cases; IIB in seven; and IIIB in
      eight. The surgical margin was intralesional in three cases; marginal in three;
      wide in six; and radical in six. In one case the surgical margin could not be
      assessed and one patient was not operated. One patient developed a recurrent
      tumour and one developed nodal metastases. Eight patients who did not have
      metastases at the time of diagnosis developed metastase during follow-up.
      Fourteen patients died of metastatic disease; one patient died of diabetes; one
      is alive with disease; and four presently do not have evidence of disease.
      CONCLUSIONS: The outcome was poor, especially due to the occurrence of pulmonary
      metastases. The functional result according to the MSTS was 100% in four
      patients; in one the result was 93% because of the scar and venous insufficiency.

PMID- 9591027
TI  - Treatment of benign and low-grade malignant intramedullary chondroid tumours with
      curettage and cryosurgery.
AB  - AIMS: To shed light on the controversy surrounding the methods of evaluating,
      staging and final treatment of intramedullary chondroid lesions. Controversy
      particularly exists for enchondroma and low-grade chondrosarcoma located in the
      extremities, because their accurate distinction is hampered by their
      radiographical and histological similarity. METHODS: Since 1991 we have treated
      22 patients (mean age: 39.6 years) with 26 lesions (three chondroblastomas, 14
      enchondromas and nine grade 1 chondrosarcomas) with curettage, cryosurgery and
      bone grafting. RESULTS: After a mean follow-up of 26 months no recurrences were
      observed. Complications consisted of two post-operative fractures, one wound
      infection and one intraoperative venous gas embolism. All bone grafts
      incorporated, resulting in full weight-bearing capacity and excellent functional
      results. CONCLUSION: The usefulness of a combination of curettage and cryosurgery
      as adjuvant therapy is considered to be equal to marginal resection according to
      orthopaedic oncological principles. The pre-operative assessment of these lesions
      and cryosurgical technique is described in detail.

PMID- 9591028
TI  - Treatment of liver metastases from uveal melanoma by combined surgery
      chemotherapy.
AB  - AIMS: To investigate sporadic results demonstrating prolonged survival after
      surgical resection and/or intraarterial chemotherapy (IACH) for liver metastases
      from uveal melanoma. METHODS: From December 1992 to March 1997 every patient with
      liver metastases from uveal melanoma was enrolled in a prospective study
      including: (1) aggressive surgical approach removing as much liver disease as
      possible; (2) implantation of an intraaterial catheter; (3) intraarterial
      chemotherapy for 6 months. 75 patients were enrolled: 38 men, 37 women, mean age
      51 years (range: 18-72), mean time from initial diagnosis of uveal melanoma to
      liver metastases 37 months (ranged: 1-168). RESULTS: Disseminated disease in both
      lobes was present in all but one patient. Macroscopically curative surgery was
      possible in 27.5%. Significant tumour reduction was performed in 49.3% and a
      simple biopsy was possible in 23.2%. Eight patients did not receive chemotherapy
      and died soon after. IACH included Fotemustine and/or DTIC-Platinum for 4-9
      cycles. Overall median survival was 9 months; very similar to non-operated
      historical controls. In the 61 patients receiving complete treatment surgery plus
      chemotherapy, median survival improved to 10 months. When curative resection was
      possible, survival increased to 22 months (P < 0.001). CONCLUSIONS: Aggressive
      surgical resection, when possible, appears to be the best method of improving
      survival of liver metastases from uveal melanoma. New drug combinations are also
      required to improve survival.

PMID- 9591029
TI  - Adenocarcinoma of the urachus: radical or conservative surgery? A report of a
      case and a review of the literature.
AB  - AIMS: To identify the most appropriate surgical strategy for carcinoma of the
      urachus. METHODS: Analysis of a case of adenocarcinoma of the urachus and an
      examination of the current literature were carried out. CONCLUSIONS: Partial
      cystectomy is considered the most appropriate surgical strategy but the need for
      close follow-up is underlined.

PMID- 9591030
TI  - Scientific information sourcing in the electronic age.

PMID- 9591031
TI  - Hypercalcaemia in patients with cancer: aetiology and treatment.
AB  - Hypercalcaemia is one of the most common disorders occurring in patients with
      cancer and may have disabling symptoms. The mechanisms underlying hypercalcaemia
      associated with malignant disease, the symptoms attributable to and the treatment
      of this disorder are discussed in this paper.

PMID- 9591032
TI  - Port site metastasis from synchronous primaries of the colon and ovary following
      laparoscopic cholecystectomy.
AB  - We report two cases of port site metastasis as the presenting feature of colonic
      and ovarian carcinoma after laparoscopic cholecystectomy. Cholecystectomy was
      performed for upper abdominal pain and gallstones. Six and 4 months after the
      operation the patients presented with nodules at port sites, other than the site
      of extraction. Biopsy proved both to be adenocarcinoma and further management
      found these to be from advanced caecal and ovarian carcinomas.

PMID- 9591033
TI  - Intracardiac extension of tumour thrombus from a soft tissue sarcoma.
AB  - We present a case of malignant peripheral nerve sheath tumour in a patient with
      von Recklinghausen's neurofibromatosis with intracardiac extension of the tumour
      thrombus. This is the first reported case of a soft tissue sarcoma associated
      with transluminal propagation of a tumour thrombus to the heart.

PMID- 9591034
TI  - Carney's triad.
AB  - The purpose of this study is to provide an overview of cases of Carney's triad
      and to discuss the clinical implications of this diagnosis. A search was made of
      the English-language literature for original articles, reviews and abstracts
      addressing Carney's triad. A new patient was described and added to the number of
      known patients. In literature 40 patients were found with a complete or
      incomplete triad. There exists no agreement on the pathology and possible common
      origin of these tumours. Directions are given for diagnostics and therapy. The
      diagnosis of Carney's triad has specific clinical implications that make a good
      knowledge of this syndrome mandatory.

PMID- 9591035
TI  - Localization of monoclonal antibody CC49 in colonic metastasis from renal cell
      carcinoma.
AB  - We report a rare case of solitary metastasis from renal cell carcinoma which
      manifested as a primary colonic tumour 5 years after nephrectomy. A monoclonal
      antibody CC49 (anti-TAG-72 antibody), used in Radioimmunoguided Surgery, was
      found to localize in the tumour. Pathological examination revealed metastasis of
      renal cell carcinoma in the colon. Immunohistochemistry with CC49 showed moderate
      staining of the colonic mucosa around the metastasis with no reaction in the
      tumour itself. Based on this case and other published studies, we conclude that
      TAG-72, the antigen manifested in many adenocarcinomas, can be up-regulated and
      expressed in normal colonic mucosa adjacent to another tumour as a result of
      stimulations, such as cytokine release, in response to this tumour.

PMID- 9591036
TI  - Rupture of the spleen in a patient with metastatic angiosarcoma of the breast.
AB  - Angiosarcoma of the breast is a rare tumour. We report a young woman who required
      an urgent mastectomy for bleeding. Metastatic disease resulted in her spleen
      rupturing after minor abdominal trauma. This has not been previously described.

PMID- 9591037
TI  - Pre-operative diagnosis of malignant mesothelioma of tunica vaginalis testis by
      hydrocele fluid cytology.
AB  - Malignant mesothelioma of tunica vaginalis testis is a rare tumour usually
      associated with hydrocele. Until now only one case has been documented, where a
      pre-operative diagnosis was made by cytological examination of hydrocele fluid.
      We report one more case with pre-operative diagnosis using hydrocele fluid
      cytology.

PMID- 9591038
TI  - Sister Joseph's nodule.

PMID- 9591039
TI  - Current management of ductal carcinoma in situ.

PMID- 9591040
TI  - [79th German Congress of Radiology. Wiesbaden, 20-23 May 1998. Abstracts].

PMID- 9591041
TI  - Identification of a differential expression of two cDNAs between malignant
      mesothelioma and normal mesothelial cells using the RNA fingerprint method.
AB  - The RNA fingerprint method was used to identify mRNAs that were differentially
      expressed during the development of human mesothelial cell cancer. We report the
      isolation of two differentially expressed clones. One clone was expressed in the
      metastatic mesothelioma cell line M1A and in the malignant mesothelioma cell line
      M1 and downregulated in normal mesothelial cells. M1 and M1A were derived from a
      primary and metastatic tumor of the same patient. The other clone was only
      expressed in normal mesothelial cells. The different expression pattern was
      confirmed by Northern blot analysis. One clone had a striking sequence homology
      to the soares pregnant uterus NbHPU homo sapiens cDNA clone. The other clone
      contained a high sequence homology to the human mRNA for ORF. The biological
      function of the corresponding genes is unknown. The specificity of expression of
      the two sequence tags was further examined on different cancer cell lines and
      normal tissues.

PMID- 9591042
TI  - Serum and cystic fluid levels of soluble interleukin-2 receptor-alpha in patients
      with epithelial ovarian tumors are correlated.
AB  - At the diagnosis of ovarian cancer, patients have higher serum levels of soluble
      interleukin-2 receptor-alpha (IL-2R alpha) compared to patients with benign
      ovarian tumors or healthy blood donors (means of 750 vs. 469 and 390 U/ml,
      respectively, p < 0.001). Serum levels were positively related to the extent of
      the disease. Disease progression was associated with rising serum levels of IL-2R
      alpha in 13 of the 15 patients but no advantage was recognized over serum CA 125
      measurements when following the effect of therapy. We measured higher levels of
      IL-2R alpha in cystic fluids from epithelial ovarian cancers compared to benign
      ovarian tumors (means of 1,620 and 616 U/ml, respectively, p = 0.0002). In
      ovarian cancer patients, serum levels at diagnosis were positively correlated to
      cystic fluid levels (p < 0.0001). The presence of high IL-2R alpha levels in
      cystic fluids from epithelial ovarian cancer may provide a biochemical signal of
      lymphocyte activation at the tissue level.

PMID- 9591043
TI  - Rapid quantitative PCR determination of relative gene expression in tumor
      specimens using high-pressure liquid chromatography.
AB  - A reverse transcriptase polymerase chain reaction (rt-PCR) for quantification of
      gene expression has been optimized for analysis of folylpolyglutamate synthase
      (FPGS) and thymidylate synthase (TS), using beta-actin as an internal standard
      (house-keeping gene). Total RNA was isolated from tumor tissue, reversely
      transcribed to cDNA and PCR amplified with primers specific for TS, FPGS and beta
      actin in separate vials. PCR products were separated and quantified by high
      pressure liquid chromatography (HPLC) without addition of radioactive or
      fluorescent markers, which minimizes labor and occupational hazards. The day-to
      day variation in the HPLC analysis was 2.7% and the within sample variations for
      rt-PCR/HPLC analysis of TS and FPGS were 18.5% for both assays. This method
      provides a tool for convenient gene expression analysis in clinical biopsies.

PMID- 9591044
TI  - High-grade malignant non-Hodgkin's lymphomas differ from low-grade lymphomas in
      the extent of apoptosis and their expression of bcl-2, mcl-1, bax and p53.
AB  - In this study, we investigated the extent of apoptosis in 82 non-Hodgkin's
      lymphoma and 4 reactive follicular hyperplasias and correlated the findings with
      the extent of apoptosis as determined by the 3'-end labelling method of the
      apoptotic DNA. To study the influence of apoptosis-regulating proteins bcl-2,
      bax, mcl-1 and p53 on the extent of apoptosis, we also immunostained the samples
      with antibodies to them. The results show that there is a significant difference
      in the extent of apoptosis between low- and high-grade non-Hodgkin's lymphomas,
      the latter on average showing considerably more apoptotic cells (0.38 +/- 0.30
      and 1.44 +/- 1.35%, respectively; p = 0.001). In line with this difference, high
      grade lymphomas had significantly more cases with a weak expression of bcl-2 and
      strong expression of bax (p = 0.00008 and p = 0.016, respectively). They also
      showed significantly more cases with a positive p53 immunoreactivity (p <
      0.00001) and strong mcl-1 immunoreactivity (p = 0.018). The results suggest that
      apoptosis-affecting genes bcl-2, bax, mcl-1 and p53 all take part in the
      regulation of apoptosis in malignant non-Hodgkin's lymphomas and contribute to a
      different level of apoptosis between high- and low-grade non-Hodgkin's lymphomas.

PMID- 9591045
TI  - An enzyme-linked immunosorbent assay for the measurement of circulating
      antibodies to polymorphic epithelial mucin (MUC1).
AB  - INTRODUCTION: About one-third of breast and ovarian carcinoma patients have
      circulating antibodies reactive with polymorphic epithelial mucin (MUC1), either
      free or bound to immune complexes. While the presence of these immune complexes
      has prognostic significance in breast cancer patients, the significance of free
      MUC1 antibodies is less clear. The objective of this study was to develop a
      reliable assay for the accurate determination of circulating free antibodies to
      MUC1. MATERIAL AND METHODS: We developed an enzyme-linked immunosorbent assay
      (ELISA) (PEM.CIg) employing a 60 mer peptide (a triple tandem repeat sequence of
      the MUC1 peptide core) conjugated to bovine serum albumin and peroxidase-labeled
      antihuman immunoglobulin G or M antibodies. The assay was standardized and its
      analytical performance evaluated. A total of 492 serum samples were obtained from
      40 healthy men, from 201 healthy women (including 55 women without a history of
      pregnancy and 45 pregnant women), and (before primary treatment) from 62 benign
      breast tumor patients and 190 breast cancer patients. MUC1 serum levels were
      determined with commercial CA 15-3 tests. RESULTS: Circulating antibodies to MUC1
      are present both in healthy subjects and in breast cancer patients. The within-
      and between-assay coefficients of variation were, respectively, 2 and 12% for the
      IgG determinations and 1.2 and 3% for the IgM determinations. Correlation
      coefficients for serially diluted serum samples ranged from 0.9998 to 0.9920 for
      IgG and from 0.9996 to 0.9818 for IgM determinations. The reactivity of serum
      samples was partially blocked by the addition of various MUC1 peptides and by
      MUC1 mucin. The inhibiting effect of modified 60 mer peptides suggests the
      presence of antibodies directed to more than one epitope. CONCLUSIONS: The PEM.
      CIg assay is a reliable ELISA for measuring free MUC1 antibodies in serum. We are
      in the process of relating the results obtained in the breast cancer group to
      disease outcome to evaluate its prognostic significance. In addition, the assay
      may become a useful tool for vaccine therapy monitoring.

PMID- 9591046
TI  - Correlation between DNA content, expression of Ki-67 antigen of tumor cells and
      immunophenotype of lymphocytes from malignant pleural effusions.
AB  - Malignant cells isolated from 26 malignant pleural effusions, collected from
      patients bearing metastatic carcinoma, were examined using flow cytometry.
      Expression of Ki-67 antigen, DNA ploidy, S phase fraction, DNA index of tumor
      cells and the percentage of aneuploid cell populations were determined. Lymphoid
      cells from the same malignant effusions and from 10 nonmalignant ones were
      examined using a panel of monoclonal antibodies (mAb) versus several CD antigens.
      While the percentages of T cells (CD3+, CD4+, CD8+) and B cells (CD19+) did not
      differ significantly in malignant versus nonmalignant effusions, those of CD56+
      lymphocytes were found to be significantly depressed in malignant diploid and
      malignant aneuploid effusions as compared to benign ones. Expression of IL-2
      receptors on lymphocytes, demonstrated by anti-CD25 mAb, was significantly higher
      in malignant diploid and malignant aneuploid effusions as compared with
      nonmalignant ones. An increase in the percentage of Ki-67-positive malignant
      cells was significantly correlated with the decrease of NK cells. S phase
      fraction, DNA index and the percentage of aneuploid populations did not correlate
      with the picture of lymphoid cells from pleural effusion. On the other hand, the
      percentage of Ki-67-positive tumor cells in pleural effusions was inversely
      proportional to the patients' survival time, although it was not statistically
      significant. Our data suggest that the poor prognosis of cancer characterized by
      the presence of an aneuploid cell population of malignant cells and the high
      percentage of proliferating cells in pleural effusions can be linked to the
      depression of NK cells.

PMID- 9591047
TI  - Analysis of the T cell receptor variability of tumor-infiltrating lymphocytes in
      colorectal carcinomas.
AB  - While there is good clinical and experimental evidence for immunological tumor
      control in some tumors--malignant melanomas, for instance--the immunogenicity of
      colorectal carcinoma (CRC) still remains unsettled. We examined surgical
      specimens from 4 CRC patients for T cell clones among tumor-infiltrating
      lymphocytes (TIL). The growth of specific lymphocyte clones in a tumor indicates
      an immunological response in vivo. We used a T cell receptor V beta family
      specific semiquantitative PCR with additional sequencing to examine TIL for
      clonal expansion. In CRC, specific T cell clones could not be demonstrated.
      However, we observed a predominance of V beta 9 in 3 of 4 tumors.

PMID- 9591048
TI  - Glycodelins.
AB  - Glycodelins are 28 to 30-kD glycoproteins synthesized in various glands, notably
      those of the male and female reproductive organs. Depending on the site of
      origin, the same protein backbone is glycosylated in different ways, yielding
      glycodelins with different biological actions. Thus, human endometrium-derived
      glycodelin-A is temporally expressed in the latter half of the menstrual cycle,
      consists of unique sialylated and fucosylated lacdiNAc oligosaccharide sequences,
      and inhibits sperm-egg binding. By contrast, glycodelin-S from seminal vesicles
      has no such oligosaccharide sequences and no contraceptive activity. Glycodelin-A
      also has potent immunosuppressive properties, and its chemically modified forms
      inhibit transmission of HIV in vitro. Studies are reviewed suggesting that
      glycoforms dictate the function of human glycodelins, and that some of the
      oligosaccharide recognition sites present in the human gametes and immune cells
      have converged.

PMID- 9591049
TI  - Cold-induced decrease of K+ conductance and its inhibition by a calmodulin
      antagonist, W-7, in Paramecium tetraurelia.
AB  - Under voltage clamp, Paramecium tetraurelia was used to examine the cold-induced
      inward current and its inhibition by a calmodulin antagonist, W-7 [N-(6
      aminohexyl)-5-chloro-1-naphthalenesulphonamide]. Cooling of the cell caused an
      inward current. The amplitude of the current was increased as the membrane
      potential was made more positive than the resting potential, and it was
      significantly blocked by using CsCl-filled electrodes and tetraethylammonium in
      the bath solution, suggesting that the current was accompanied mainly by a
      decrease in K+ conductance. The cold-induced inward current was reversibly
      inhibited by the external application of W-7 in a concentration-dependent manner.
      EGTA-microinjection into the cell also reduced the current. These results
      indicate that the decrease in K+ conductance induced by cooling is Ca(2+)
      dependent and is inhibited by W-7.

PMID- 9591050
TI  - Nuclear translocation of the catalytic component of DNA-dependent protein kinase
      upon growth stimulation in normal human T lymphocytes.
AB  - DNA-dependent protein kinase (DNA-PK), consisting of the 470-kDa catalytic
      component (DNA-PKcs) and the DNA-binding regulatory component Ku protein
      (p70/p80), catalyzes phosphorylation of a variety of DNA
      replication/transcription/repair factors in the presence of double-stranded DNA.
      In the resting states of human peripheral blood mononuclear cells, DNA-PK
      activity and the protein level of DNA-PKcs were very low in the nuclear extracts,
      but they were high in the whole cell extracts. Depending upon proliferation of
      the T lymphocytes, DNA-PK activity and the protein level of DNA-PKcs in the
      nuclear extracts greatly increased. Immunocytochemical analysis suggested
      translocation of DNA-PKcs from the cytoplasm to the nucleus upon growth
      stimulation in the T lymphocytes.

PMID- 9591051
TI  - Gene expression of lipid binding protein transferred the ability of specific
      attachment of hemopoietic cells to non-supportive stromal cell line, MS-K.
AB  - In order to identify the cDNAs responsible for hemopoietic supportive activity,
      expression of mRNAs in hemopoietic supportive bone marrow stromal cells (MS-5)
      and non-supportive stromal cells (MS-K) were compared by the cDNA subtraction
      method. A subtracted MS-5-cDNA library, which contains cDNA clones corresponding
      to mRNAs present in MS-5 cells but not in MS-K cells, was constructed. Screening
      of subtracted MS-5-cDNA library resulted in the isolation of some clones. Two of
      them, lipid binding protein (LBP) and haptoglobin (Hp), were expressed
      specifically in MS-5 cells but not in MS-K cells. The genes of LBP and Hp were
      subcloned into mammalian expression vector and transfected into hemopoietic non
      supportive stromal cells line, MS-K. Then LBP-expressing stable transformants (MS
      K-LBP) and Hp-expressing transformants (MS-K-Hp) were cloned. A rosette formation
      assay was carried out to investigate whether or not the LBP and Hp cause MS-K
      cells to adhere to hemopoietic cells. MS-K-LBP formed rosettes with hemopoietic
      cells as MS-5 cells, although the MS-K-Hp and normal MS-K cells did not form
      rosettes. These data indicate that LBP expressed in hemopoietic supportive
      stromal cells is partly responsible for the adhesion of hemopoietic stem cells to
      stromal cells.

PMID- 9591052
TI  - Assembly of basement membrane in vitro by cooperation between alveolar epithelial
      cells and pulmonary fibroblasts.
AB  - To investigate basement membrane formation by cooperation between pneumocytes and
      pulmonary fibroblasts, we cultured type II alveolar epithelial cells obtained
      from rats transfected with SV40-large T antigen gene (SV40-T2 cells) on type I
      collagen matrices. On fibroblasts-embedded gel (T2-Fgel), SV40-T2 cells
      ultrastructurally formed a continuous and thin layer of lamina densa, while on
      collagen gel without fibroblasts (T2-gel) SV40-T2 cells produced only
      discontinuous and diffuse deposits. Stripping SV40-T2 cells off the tissues by
      H2O2 treatment revealed a continuous and plane surface of lamina densa assembled
      on the T2-Fgel tissue, whereas only amorphous deposits appeared on the T2-gel
      tissue. Immunolocalization of major basement membrane components showed that type
      IV collagen, laminin, perlecan and entactin (nidogen) were continuously
      integrated on the lamina densa in T2-Fgel. In T2-gel, all these components were
      discontinuously distributed beneath SV40-T2 cells. The contribution of pulmonary
      fibroblasts to the assembly of basement membrane through reorganization of
      collagen matrix and/or soluble factors was examined by the cultured of SV40-T2
      cells on the freeze-thawed fibroblast-tissue and/or with the fibroblast
      conditioned medium. Both SV40-T2 cells on the freeze-thawed fibroblast-tissue and
      SV40-T2 cells in T2-gel in the fibroblast-conditioned medium failed to produce a
      lamina densa. SV40-T2 cells could assemble a lamina densa only on the freeze
      thawed fibroblast-tissue in the fibroblast-conditioned medium. These results show
      that the basement membrane components are assembled to a lamina densa by
      combination of the reorganization of collagen matrix and the supply of soluble
      factors by pulmonary fibroblasts.

PMID- 9591053
TI  - Biochemical and immunocytochemical properties of peroxisomes and mitochondria in
      bovine chromaffin cells.
AB  - The biochemical and immunocytochemical properties of peroxisomal and
      mitochondrial beta-oxidation enzymes in bovine adrenal chromaffin cells were
      investigated. Peroxisomes were detectable by immunofluorescence staining using
      antibodies against acyl-CoA oxidase, peroxisomal 3-ketoacyl-CoA thiolase and
      catalase. The mitochondria were abundantly stained with antibody against
      mitochondrial 3-ketoacyl-CoA thiolase. The biosynthesis and intracellular
      processing of acyl-CoA oxidase and the peroxisomal 3-ketoacyl-CoA thiolase was
      slower than that in fibroblasts. The peroxisomal beta-oxidation activities shown
      by [1-14C] lignoceric acid oxidation were slightly lower than those in
      fibroblasts, whereas the mitochondrial beta-oxidation activities shown by [1-14C]
      palmitic acid oxidation were almost identical to those in fibroblasts. Adrenal
      chromaffin cells are useful materials for investigating the peroxisomal and
      mitochondrial metabolism of autonomic neurons and may contribute to the
      clarification of neuronal dysfunction in peroxisomal and mitochondrial disorders.

PMID- 9591054
TI  - Nuclear translocation of gold labeled-testosterone-bovine serum albumin conjugate
      through the nuclear double membranes in rat spermatids.
AB  - We have demonstrated that testosterone-bovine serum albumin conjugate labeled
      with 2-nm colloidal gold (testosterone-BSA-gold) injected into the vascular
      system of rat becomes visible as silver deposits on the sections of tissues
      embedded in epoxy resin after silver enhancement and enters the androgen-target
      cell nuclei, e.g. round spermatids, but not the non-target cell nuclei. The
      diameter of the silver deposits depends on the duration of silver enhancement. In
      this study, to make clear the transfer route of testosterone-BSA-gold into the
      round spermatid nucleus, the testis of rat injected testosterone-BSA-gold was
      observed under electron microscope after silver enhancement for short periods of
      time. The small silver deposits were present on the cell membrane, vesicles,
      Golgi region, acrosome, subacrosomal space, both the post-acrosomal and the
      subacrosomal nuclear envelope, and the nucleoplasm in the cap-phase spermatids.
      The silver deposits were also found in the perinuclear cisterna of post-acrosomal
      nuclear envelope, but not in the nuclear pore. When the spermatids were observed
      at high-power magnification without the silver enhancement, the outer nuclear
      membrane showed many irregular invaginations toward the inner nuclear membrane in
      the post-acrosomal nuclear envelope. Furthermore, a double-membrane-like vesicle
      seemed to be present in the nuclear envelope. In the vesicle, the gold particles
      were present along the inner membrane. These results suggest that testosterone
      BSA-gold can enter the nucleoplasm through some route provided by the nuclear
      double membranes in both the post-acrosomal and the subacrosomal nuclear
      envelope.

PMID- 9591055
TI  - [Clinical picture of colloid cysts of the III ventricle].
AB  - Clinical analysis of 74 cases of colloid cysts of the III-d ventricle was
      performed. Dynamics of clinical symptom complex was studied both in preoperative
      and early postoperative period as well as in remote periods after surgery. Most
      of the patients were treated in N.N. Burdenko Institute of Neurosurgery during
      1980-1995. Peculiarities of the disease development before clinical
      manifestation, variations of complicated postoperative period, prognostically
      significant symptoms, possible mechanisms of clinical syndromes development were
      considered.

PMID- 9591056
TI  - [Neurologic manifestations of sarcoidosis].
AB  - 126 patients with histologically verified mediastinal-pulmonary legions were
      examined in terms of neurologic manifestations of sarcoidosis. Systemic
      psychoneurologic observation of all patients was performed by continuous method.
      Neurologic disorders were nonmalignant, chronic, latent or transitory. Stable,
      acute or severe manifestations were registered quite seldom. Sensory, autonomic,
      neuroendocrine and neuropsychologic disorders prevailed in clinical picture.

PMID- 9591057
TI  - [Clinical characteristics of motor deficit in patients after hemispheric stroke].
AB  - Correlation between clinical structure of motor deficit and indices of
      stimulation electromyography was studied in 108 patients with hemispheric stroke.
      Methods of statistic analysis were applied including devising of histograms,
      Pareto diagrams, determination of the narrowness of correlation ratio. The
      analysis revealed complex relationship between the signs of motor deficit in
      clinical picture and the data of stimulation electromyography in patients with
      cerebral hemispheric stroke.

PMID- 9591058
TI  - [Psychopathology of alcohol abuse in schizophrenia].
AB  - Psychopathological study of primary and secondary alcohol abuse (PAA, SAA) was
      studied in 107 schizophrenic patients of 17-55 years old. Different types of PAA
      development was related to peculiarities of both schizophrenic syndromes and
      impulse control disorders. SAA development was the same as in chronic alcoholism.

PMID- 9591059
TI  - [Typology of prolonged anxious-phobic disorders with agoraphobia].
AB  - There were studied 23 schizophrenic and cyclothymic patients with stable
      agoraphobia in the structure of anxiousphobic disorders (APD). No absolute
      correlation was found between stability of agoraphobia and severity of panic
      disorder (frequency and intensity of panic attacks). It was established that APD
      with manifestations of agoraphobia had been, perhaps, conditioned by the presence
      of comorbid disturbances in their structure which had determined peculiarities of
      the patients' behavior. Two types of prolonged APD with agoraphobic phenomena
      were recognized. Retention of agoraphobic disturbances in conditions of the first
      type was related to symptoms of generalized somatic disorder (generalized somatic
      anxiety) in clinical pattern of APD. Manifestations similar to panphobias
      prevailed, agoraphobic avoidance included all the situations in which the patient
      could find himself without help. In the states of the second type retention of
      agoraphobic disorders was conditioned by comorbidity of APD with
      asthenohypochondriac manifestations with somato-psychic fragility in their
      structure. Anxiety of expectation was formed in situations with emotional or
      physical tension. Agoraphobic avoidance in conditions of this type had displayed
      the character of preventive measures and one of manifestations of hypochondriac
      development of personality. The presence of pronounced anxiety (intensive panic
      attacks, generalized anxiety) in clinical pattern of prolonged agoraphobic
      conditions can serve a predictor of a favourable development of the disease.

PMID- 9591060
TI  - [Betaferon--first experience of application in treatment of multiple sclerosis in
      Russia].
AB  - 32 patients (21-55 years old) with multiple sclerosis (MS) were treated.
      Remittent form of the disease was observed in 24 patients, secondary progressive
      one--in 8 individuals; the degree of disability was characterised as scores 0-3
      (the first group) and scores 5-6 (the second one) according to scale EDSS.
      Betaferon was administered subcutaneously in the dose of 8 MIU every other day
      during the period from several months to 1 year and more. Improvement of the
      state was observed in 5 patients with remittent form, stop of the development of
      disease (absence of either aggravations or signs of MS progression) was found in
      26 cases (21 with remittent form, 4 with secondary progressive form). The
      conclusion was made: betaferon cannot cure but can stop progression of the
      disease. Indications and contraindications for betaferon therapy were established
      and recommendations were given concerning regimen of the treatment prophylaxis
      and therapy of side-effects.

PMID- 9591061
TI  - [Magnetic stimulation in restorative therapy of patients with spondylogenic
      diseases of nervous system].
AB  - A new method of impulse magnetic therapy was studied in the treatment of
      neurologic complications of osteochondrosis and deforming spondylarthrosis in 225
      patients with neurologic manifestations of pathology in cervical or sacral parts
      of spinal column. To assess the results obtained, EMG, thermography and
      determination of the levels of blood plasma lipid peroxidation were used.

PMID- 9591063
TI  - [DNA-diagnosis of bulbospinal muscular atrophy (Kennedy's disease)].
AB  - Bulbospinal muscular atrophy--a rare disease with X-linked recessive type of
      inheritance. It is caused by expansion of trinucleotide repetitions in the gene
      of androgenic receptor (AR). We elaborated a method of DNA-testing with usage of
      nonradioactive registration of mutant alleles of AR gene. DNA-diagnosis was
      performed in 16 patients with clinical pattern of bulbospinal muscular atrophy
      and diagnosis was confirmed in 11 patients. Carriage of mutant alleles was found
      in 7 women--relatives of the patients. Presymptomatic diagnosis revealed the
      presence of mutant alleles in 2 boys. Unstability of alleles of mutant AR gene
      was observed in one family: in sons there was more (upon 5) of CAG-triplets.

PMID- 9591062
TI  - [Choice of therapeutic tactics in treatment of endogenous depression by means of
      statusmetric expert system].
AB  - There was elaborated expert models based on computer data base including 42
      formalized signs (anamnesis, state of the patients, medical measures and indices
      of expert estimation of the response to therapy, based on the reduction of scores
      of Hamilton's scale). The study was carried out in 104 in-patients whose clinical
      states corresponded according to ICD-10 to category "depressive episode" and
      "recurrent depressive disorder". The patients were divided into 2 groups: in the
      first one the treatment was performed by serotoninergic antidepressants (SA)
      fluoxetine (20 patients), fluvoxamine (20), sertraline (30). Tricyclic
      antidepressant (TAD) amitryptiline was administered to 34 patients of the second
      group. Two data bases were formed: responders to TAD and responders to SA.
      Natural pair model of classification (error of the model--12.5%) including 9
      informative signs, was constructed, that gave chance to define probability
      sensitivity to TAD and SA. Check-up of computer model revealed that 3 patients of
      SA group didn't submit to decisive rule, while there were found 2 such patients
      in TAD application. Application of computer experiment permitted to turn from
      group prognosis to individual one.

PMID- 9591064
TI  - [Synaptic contacts in schizophrenia: study with immunocytochemical identification
      of dopaminergic neurons].
AB  - Immunocytochemical identification of dopaminergic neurons was made by means of
      immunoperoxidase method using antibodies to tyrosine hydroxylase. The
      ultrastructure of synaptic contacts located on dopaminergic (tyrosine hydroxylase
      immunopositive--TP) neurons was investigated in substantia nigra (SN) of
      postmortem brains in 4 schizophrenic patients compared to 3 mentally healthy
      control cases. Various alterations of ultrastructure have been found in
      presynaptic terminals which contracted with TP neurons in SN of schizophrenic
      patients as compared to the control group. These alterations included:
      presynaptic axon terminals decreased in sizes with dense matrix and density
      packed vesicles; swollen terminals with clustering of synaptic vesicles and
      displaced active zone of synapse; hyperplasia of mitochondria in the part of
      presynaptic boutons; appearance of abnormal membranous lamellar structures inside
      or outside presynaptic boutons. The altered presynaptic terminals were
      preferentially located on distal (small and middle diameter) TP dendrites in pars
      compacta of SN, where practically all dendrites revealed belonged to dopaminergic
      neurons and formed asymmetric contacts with short active zones in most cases. The
      changes of ultrastructure of synaptic contacts could be rarely observed in SN
      pars reticulata of schizophrenic patients both on TP and tyrosine hydroxylase
      immunonegative dendrites presented here.

PMID- 9591065
TI  - [Peripheral autonomic insufficiency].

PMID- 9591066
TI  - [Diagnosis of meningiomas of cerebral hemispheres at prehospital stage].

PMID- 9591067
TI  - [Classification and perspectives of development of methods for diagnosis of
      traumatic neuropathies].

PMID- 9591069
TI  - [Diagnosis and treatment of craniovertebral region anomaly with the development
      of Arnold-Chiari syndrome and hydromyelia].

PMID- 9591068
TI  - [Eyelid myoclonus with absence].

PMID- 9591070
TI  - [The couvade syndrome].

PMID- 9591071
TI  - [Characteristics of damage to peripheral nervous system in Lyme borreliosis].

PMID- 9591072
TI  - [Spinal cord compression in multiple myeloma].

PMID- 9591073
TI  - [Application of magnetic stimulation in diagnosis of facial and trigeminal nerves
      impairement].

PMID- 9591074
TI  - [Autonomic alternations in mature newborns with hypoxic damage of brain].

PMID- 9591075
TI  - [Association of leprosy neuritis with thyroid status].

PMID- 9591076
TI  - [Filamentosis and Alzheimer disease].

PMID- 9591077
TI  - [Ultrastructure of cerebral cortex synapses in ontogenesis].

PMID- 9591078
TI  - [Central mechanisms of predisposition to psychoactive substance dependence].

PMID- 9591079
TI  - [Role of enteroviruses in pathology of nervous system].

PMID- 9591080
TI  - [Herpetic encephalitis with mental disorders].

PMID- 9591081
TI  - [Modern methods of diagnosis in traumatic and ischemic myelopathies].

PMID- 9591082
TI  - [Methodology of efficiency estimation in rehabilitation of neurologic patients].

PMID- 9591083
TI  - [Clinical aspects of astroglia's pathology].

PMID- 9591085
TI  - 67th Annual meeting of the American Associations of Physical Anthropologists.
      Salt Lake City, Utah, USA. March 31-April 4, 1998. Abstracts.

PMID- 9591084
TI  - [World congress on Rett syndrome].

PMID- 9591087
TI  - Author and subject indexes to volumes 22-29.

PMID- 9591086
TI  - 7th Workshop on Cell Biology of Bone and Cartilage in Health and Disease and 4th
      Workshop on Bisphosphonates--from the Laboratory to the Patient. Davos,
      Switzerland, March 1998. Abstracts.

PMID- 9591088
TI  - Euro-Neuro '98: 1st International update on Neuro-Anaesthesia and Neuro-Intensive
      Care. Genk, Belgium, 5-7 February 1998. Abstracts.

PMID- 9591089
TI  - 30th Annual meeting of the American Burn Association. Chicago, Illinois, USA.
      March 18-21, 1998. Abstracts.

PMID- 9591090
TI  - [Standards of diagnostic imaging in oncologic liver surgery. Hannover, 1 November
      1997].

PMID- 9591091
TI  - [German Society for Thoracic and Cardiovascular Surgery honorary members].

PMID- 9591092
TI  - 27th Annual meeting of the German Society In Thoracic and Cardiovascular Surgery.
      Dresden, February 18-21, 1998. Abstracts.

PMID- 9591093
TI  - [Phenothiazine drugs as photosensitizers and photoprotectors].
AB  - The photosensitizing properties of eight N-alkylated phenothiazine neuroleptic
      drugs were studied. The experiments were carried out in a model system based on
      photooxidative chemiluminescence of Gly-Trp peptide in aqueous solution. Under
      irradiation with light longer than 280 nm, all the studied phenothiazine
      derivatives decrease the chemiluminescence intensity at low concentrations and
      enhance it at high concentrations. Phenothiazine derivatives is likely to be due
      to superoxide and/or Gly-Trp free peroxide radicals. Photosensitization begins to
      dominate over protection at concentrations which are different for various
      phenothiazine derivatives compounds and lie in the range 10(-6)-10(-5) M. The
      photosensitizing efficiency decreases in the order: Thioproperazine,
      Trifluoperazine Hydrochloride, Alimezine, Thioridazine Hydrochloride,
      Levomepromazine Hydrochloride, Promethazine Hydrochloride, Periciazine,
      Chlorpromazine Hydrochloride. It was shown that photooxidation of Gly-Trp
      sensitized by phenothiazine derivatives occurs via singlet oxygen formation.

PMID- 9591094
TI  - [Antioxidant properties of plant extracts].
AB  - Investigation of antioxidant properties of some plants was carried out. A group
      of plants exhibited antimicrobial activity was studied in detail. Efficiency of
      plants as antioxidants was tested by the influence of their extracts on the yield
      of photochemiluminescence of Gly-Trp solutions. Antioxidant properties were
      examined under conditions when their own absorption was minimized. Riboflavin as
      additional sensitizer was used in this experiment for superoxide generation. The
      antioxidant effect was evaluated with regard to single dose of plant extracts and
      their concentration in human organism. The effect decreases in the following
      consequence: Hypericum perforatum > Potentilla erectra > Ledum palustre >
      Plantago major > Salvia officinalis > Chamomilla recutita > Arctostaphylos uva.

PMID- 9591095
TI  - [Mechanism of quenching of hematoporphyrin and mono-L-aspartyl chlorine e6
      triplet states by metronidazole].
AB  - The quenching of the triplet state of hematopophyrin (3HP.) and mono-L-aspartyl
      chlorine e6, (3MACE.) by metrotlidazole (METRO) ground state, has been
      investigated in binary mixtures of water and aliphatic alcohol by means of 532 nm
      laser flash. In water, both 3HP. and 3MACE. quenched by METRO with at rate: kQw =
      1.9 x 10(9) M-1.s-1. The quenching is accompanied by the appearance of a
      transient absorbance near 690 nm. This transient absorbance corresponds to the
      tetrapyrrole radical-cation formation in result of an electron transfer between
      3HP. or 3MACE. and METRO. In neat alcohol, the electron transfer was not
      observed. In binary mixtures the quenching constant is reduced as the molar
      fraction of water is decreased. In water, the activation barrier of the quenching
      is 5.9 kcal/mol for HP and 3.9 kcal/mol for MACE. In going from water to water
      alcohol mixtures the energy of activation is practically unchanged. Based on
      flash photolysis data, and analysis of absorption spectra of METRO we conclude
      that the electron-acceptor ability of metronidazole essentially depends on the
      intermolecular interaction with nearby solvent molecules. The mechanism of the
      quenching is discussed.

PMID- 9591096
TI  - [1H-NMR study of complex formation between the aromatic dye ethidium bromide and
      the single-stranded noncomplementary deoxytetranucleotide 5'-d(CpTpGpA) in
      aqueous solution].
AB  - Complex formation between the aromatic dye ethidium bromide (3,8-diamino-6-phenyl
      5-ethylphenanthridine) and the single-stranded noncomplementary
      deoxytetranucleotide 5'-d(CpTpGpA) in aqueous solution was studied by one- and
      two-dimensional 1H NMR spectroscopy (500 and 600 MHz). Complete assignments of
      proton signals from the deoxytetranucleotide 5'-d(CTGA) were made using 2D-TOCSY
      and 2D-NOESY spectra. The concentration dependences of proton chemical shifts of
      the tetranucleotide were measured at T = 298 K to determine the self-association
      constants of tetranucleotide molecules in solution. Due to a small probability of
      tetranucleotide duplex formation, the complexing of dye molecules with the
      monomer of the tetramer plays the main role in the equilibrium of the complex in
      solution, which makes it possible to analyze the specificity of interactions of
      the aromatic ligand with the single-stranded DNA. Different schemes of complex
      formation were examined, and equilibrium constants for the reactions and the
      limiting chemical shifts of dye protons in different complexes were determined.
      The relative content of different types of complexes was analyzed, and specific
      features of the dynamic equilibrium were revealed as a function of the dye
      tetranucleotide concentration ratio. The analysis indicates a sequence-specific
      binding of ethidium bromide to the single-stranded oligonucleotide. The
      structures of 1:1 complexes of the dye with the single strand of the
      tetranucleotide that correspond to two most probable orientations of the dye
      chromophore in the pyrimidine-purine T-G-site of the tetramer base sequence were
      constructed using the calculated values of induced chemical shifts of ethidium
      bromide protons.

PMID- 9591097
TI  - [Estimation of quality of approximation of atom-atom contacts of amino acid
      residues in proteins by the contacts of the residue force centers].
AB  - How precisely the atom-atom contacts of amino acid residues in proteins can be
      approximated by the contacts of amino acid residue "force centers"? To answer
      this question, we examined the force centers positioned in the C alpha-atom, the
      C beta-atom, in the optimal point of the C alpha-C beta axis, and in the
      geometrical center of residues. The maximal coefficient of correlation between
      the residue force center contacts and the presence of atom-atom contacts of the
      residues (85%) was obtained for the force centers positioned in geometrical
      centers of the residues. The correlation is 80% for the optimal position of the
      centers on the C alpha-C beta axes; a somewhat smaller value (78%) is obtained
      for the force centers positioned in C beta-atoms, and 71% only for the centers
      positioned in C alpha-atoms. The obtained results allow one to estimate the limit
      of precision of calculations which replace the atom-atom interactions by
      interactions of amino acid residues taken as a whole.

PMID- 9591099
TI  - [Stabilization of optical characteristics of DNA cholesteric liquid-crystalline
      dispersions].
AB  - Abnormal optical properties of liquid-crystalline dispersions (phases) formed as
      a result of phase exclusion of double-stranded DNA and RNA from water-salt
      poly(ethylene glycol) solutions and X-ray parameters of these phases are
      compared. It is shown that the cholesteric packing of nucleic acid molecules is
      realized at the certain osmotic pressure of a solvent only. A comparison of the
      optical properties of liquid-crystalline phases (dispersions) to their X-ray
      parameters allows one to put forward a suggestion on various hydratation
      (fluctuation) regimes of the nucleic acid behaviour under the condensed phases
      formation and factors, influencing the mode of packing of these molecules in
      phases formed. It is shown as well, that immobilization of DNA cholesteric liquid
      crystalline particles in the content of polymeric matrix is accompanied by the
      stabilization of these particles and, hence, their specific abnormal optical
      activity as well as by formation of particles having a structure, which
      corresponds to the "optically isotropic ordered liquid" without abnormal optical
      activity. Data on stabilization of the cholesteric structure of liquid
      crystalline DNA dispersions by creation of polymeric chelate bridges between the
      neighbouring DNA molecules, fixed in the structure of liquid-crystalline
      dispersions, are shown.

PMID- 9591098
TI  - [Influence of kinetic factors on heat denaturation and renaturation of
      biopolymers].
AB  - Possible influence of experimental nonequilibrium conditions on heat denaturation
      and renaturation of biopolymers has been studied. The analysis has been made
      using a standard kinetic model of transition between two states. Regularities are
      revealed which determine the position and shape of the heat absorption peak in
      calorimetric experiments on direct and reverse scanning (heating and cooling).
      The evaluation formulas for obtaining kinetic information from such experiments
      are given and their application is discussed. The results obtained can be useful
      in analysis of real calorimetric curves. It is shown that upon heating and
      cooling in nonequilibrium conditions the behavior of the system can differ
      qualitatively. The above difference takes place when the renaturation rate
      decreases on lowering the temperature. In this case, heating under nonequilibrium
      conditions leads only to a shift of denaturation transition to the higher
      temperatures while nonequilibrium cooling may result in complete or partial
      irreversibility.

PMID- 9591100
TI  - [Changes of liposomes electrophoretic mobility under the effect of ribonuclease
      and cytochrome c].
AB  - The effect of ribonuclease and cytochrome c on electrophoretic mobility of
      liposomes composed of phosphatidylcholine and diphosphatidylglycerol has been
      studied. zeta-Potential of lipid vesicles was found to decrease in the presence
      of proteins. Parameters of proteins binding to phospholipids were evaluated from
      the changes of surface charge density of model membranes. The constants of
      protein association with phospholipids were calculated to be about 4 x 10(4) M-1
      for ribonuclease and about 5.4 x 10(4) M-1 for cytochrome c.

PMID- 9591101
TI  - [Two-parameter flow fluorescence analysis of human chromosomes. Quantitative
      processing].
AB  - A procedure for the quantitative analysis of the results of fluorimetric studies
      on human chromosomes in a flow is described. The procedure enables one to
      simultaneously follow two parameters by using two fluorochromes, one of which is
      selective to the GC-, and the other, to AT base pairs of DNA. Thus, it becomes
      possible to derive from the experimentally obtained distributions an information
      on the relative DNA content in individual chromosomes, differences in DNA content
      between homologous chromosomes, the relative number of chromosomes of each type
      in the sample tested, as well as on the percent ratio of AT and GC base pairs in
      a particular chromosome. In addition, the procedure enables one to assign, with a
      high degree of accuracy, the peaks on experimental distributions to the objects
      of analysis chromosomes. The analysis cutting off the extreme combines the method
      of components with the least square method, as applied to the peaks of the
      Gaussian shape. The first step involves the filtration of the starting
      experimental data from contaminating signals from both the parts of degraded
      chromosomes and stained cytoplasm fragments, and from chromosome aggregates. The
      procedure is realized as a package of programs for IBM-compatible PC/AT computers
      (486 and later versions), which permits one to perform a comprehensive analysis
      of two-parameter distributions of chromosome fluorescence signals to solve a
      number of problems, such as the identification of chromosome aberrations in cell
      lines tested, quantitative comparison of distinguishing features of homologous
      chromosomes and whole chromosome sets.

PMID- 9591102
TI  - [Current-voltage characteristics of bilayer lipid membranes formed on the
      substrates].
AB  - Current-voltage characteristics (CVC) of bilayer lipid membranes formed on the
      support (s-BLM) were measured in static mode as well as in cyclic one with the
      period 33 s. The new cut of the wire from stainless stell SS-10T served as the
      support. In the range of voltages -0.9-(+)0.9V the similarity of the CVC for s
      BLM as well as for support- electrolyte border was observed. Static CVC for both
      objects satisfy the Tafel's equation with close parameters. If the voltage
      amplitudes were over 0.3 V, s-BLM specific capacitance approached the same value
      for the support-electrolyte border. Possible electrical models of s-BLM are
      discussed.

PMID- 9591103
TI  - [Intramolecular bond ordering of cis-octadecadienoic chains of natural lipids.
      Monte-Carlo simulation].
AB  - The Monte Carlo method is applied in the calculation of C-C and C-H bond
      orientation distributions rho(theta) with respect to the maximum molecule span
      axis (theta is the angle between the bond and the axis) and bond order parameters
      SCC and SCH of isolated unperturbed hydrocarbon chains of cis -C18;2 at T = 298
      K. The molecule-fixed coordinate system is used. The relation of the bond
      orientation distributions rho(theta) to the order parameters S are analysed in
      terms of angles theta max (a "geometric" factor, rho(theta max) = max) and widths
      delta theta of the distributions (factor of "fluctuations"). The results indicate
      that the fluctuation factor depends on both the segment chemical structure and
      location in the chain. The two delta theta values of C-H-bonds flanking the
      double bond are smaller than that obtained for adjacent CH2-groups by a factor of
      1.5-2. The C = C double bond parameters SCC are found to be higher than those of
      adjacent single C-C bonds. The order parameter profiles -SCH obtained from the
      simulations (at the portion which corresponds to the double bonds location) are
      in qualitative, agreement with experimental data on the bilayer in the liquid
      crystal phase.

PMID- 9591104
TI  - [How can we measure a diameter of each entrance of a ion channel recording only
      channel conductance?].
AB  - The channel formed by colicin Ia in planar lipid bilayer was used to develop a
      method determining a diameter of each channel entrance. The method is based on
      measuring of a channel filling with nonelectrolytes through cis- and trans
      entrance separately. To do this, one need to establish the two things only: the
      conductance of an ion channel and the conductivity of used solutions. Using the
      method to predict the internal geometry of a channel lumen is discussed.

PMID- 9591105
TI  - [Mathematical modeling of energy coupling in mitochondria in frames of proton
      chemical hypothesis].
AB  - The dependence of ATP-synthesis and mitochondria respiration rates on membrane
      potential was analyzed in frames of proton-chemical hypothesis of oxidative
      phosphorylation. The mathematical and electrical models of the unit of energy
      coupling are proposed. Computer analysis of the mathematical model allowed to
      obtain the theoretical dependence of the rates of ATP synthesis and of the
      respiration on the membrane potential. Both of all are in good qualitative
      agreement with experimental data, contradicting chemiosmotic hypothesis.

PMID- 9591107
TI  - [Difference in inhibitory actions of products of the myeloperoxidase- catalyzed
      reaction on initial aggregation of activated platelets].
AB  - Inhibition of the initial aggregation of isolated rabbit platelets was studied on
      two types of their stimulation. The stimuli were either ADP, which was also
      capable to induce cell rounding, or adrenaline, and CaCl2, which acted without
      cell rounding. When platelets are stimulated by adrenaline or calcium chloride,
      sodium hypochlorite enhances the anti-aggregatory effect: at a concentration of
      about 10 microM the aggregation is reduced by 50%. This inhibitory effect is 1.5
      3 times the ADP-stimulated inhibition of the aggregation of platelets or the
      inhibition of platelet aggregation by N-chloralanine under activation of
      platelets by any stimulus. Dithionitrobenzoic acid, which is a widely used
      reactant for sulfhydryl groups, also suppresses the platelet aggregation. Its
      inhibitory effect is similar to the of antiaggregatory action of sodium
      hypochlorite on platelets. It is not excluded that the enhanced antiaggregatory
      effect of sodium hypochlorite is due to an alteration of calcium channels in
      platelet plasma membranes, which occurs with the involvement of sulfhydryl
      groups.

PMID- 9591106
TI  - [Acidosis inhibits oxidative phosphorylation in intrasynaptosomal mitochondria by
      releasing calcium from cytoplasmic store].
AB  - The origin of calcium responsible for earlier observed acidosis-induced decrease
      in ATP content and inhibition of respiration in rat brain synaptosomes was
      studied. Acidosis (pH 6.0) inhibits both basal and potassium-stimulated 45Ca2+
      uptake (60 mM KCl). Calcium channel blockers verapamil (100 microM) and 45Ca2+
      (100 microM) have no effect on the level of ATP and respiration rate at pH 6.0.
      Theophylline (10 mM) releasing calcium from intracellular stores lowered ATP and
      O2 consumption rate at pH 7.4 but not at pH 6.0 being effective only in calcium
      containing medium. Inhibitor of calcium transport in mitochondria ruthenium red
      (10 microM) prevented acidosis-induced ATP decrease. It is suggested that
      acidosis inhibits oxidative phosphorylation by releasing calcium from cytoplasmic
      stores with its subsequent transport into intrasynaptosomal mitochondria.

PMID- 9591108
TI  - [Mathematical model of the mechanical properties of skeletal muscle fibres taking
      into account compliance of the actin filaments].
AB  - A mathematical model describing mechanical transients induced by the step length
      changes in skeletal muscle fibres is suggested. The model takes into account
      compliance of actin filaments and the cross-bridge mechanics. Two different
      approaches were used for modeling of the cross-bridges: the Huxley-Simmons (1971)
      model and a new nonlinear viscoelasic model. From a comparison of the results of
      computer simulation with experimental data we conclude that the best fitting is
      achieved by using a combined model where both Huxley-Simmons mechanism and cross
      bridges viscoelastisity are represented.

PMID- 9591109
TI  - [Dynamics of spontaneous beating of cardiomyocytes in vitro depend on the number
      of involved cells].
AB  - The dynamics of cardiomyocyte spontaneous beatings with fractal dimension
      calculation was studied. It was shown that isolated single cardiomyocyte beats
      stochastically, but when a number of cells synchronized a significant changes in
      the dynamics appear: deterministic chaos could be detected. Several reasons are
      discussed as a possible explanation of such a behavior: the effect of system
      volume increasing and specific influence of gap-junctions on the rhythm
      formation.

PMID- 9591110
TI  - [The reconstruction of mechanical properties of layered viscoelastic media based
      on impedance measurements].
AB  - The possibility for the reconstruction of unknown mechanical properties of
      layered media is investigated using the displacement data of rigid circular
      piston based on the extension of the solution to classical Lamb problem. The
      examples of published experimental data processing are given.

PMID- 9591111
TI  - Construct for assessment of transfected secretory proteins using an independently
      secreted reporter gene.

PMID- 9591112
TI  - On-line microdialysis for mass spectrometry.

PMID- 9591113
TI  - Single-step purification of T7 RNA polymerase with a 6-histidine tag.

PMID- 9591114
TI  - Differential mRNA display at the single-cell level.

PMID- 9591115
TI  - Simplified method for the telomeric repeat amplification protocol (TRAP).

PMID- 9591116
TI  - Artifact occurring during combined in situ hybridization and immunocytochemistry
      analysis because of positive chemography.

PMID- 9591117
TI  - DNase I treatment of total RNA improves the accuracy of ribonuclease protection
      assay.

PMID- 9591118
TI  - Fusion PCR, a one-step variant of the "megaprimer" method of mutagenesis.

PMID- 9591119
TI  - Real-time fluorescence detection of a single DNA molecule.

PMID- 9591120
TI  - One-step procedure for screening recombinant plasmids by size.

PMID- 9591121
TI  - Enhanced efficiency of cloning FACS-sorted mammalian cells.

PMID- 9591122
TI  - Isolation of stable bacterial artificial chromosome DNA using a modified alkaline
      lysis method.

PMID- 9591123
TI  - Rapid zymogram for lipase.

PMID- 9591124
TI  - Modified Hirt procedure for rapid purification of extrachromosomal DNA from
      mammalian cells.

PMID- 9591125
TI  - Concentrating dilute protein solutions for gel electrophoresis.

PMID- 9591126
TI  - Minimizing false positives in differential display.

PMID- 9591127
TI  - Vectors for expressing T7 epitope- and His6 affinity-tagged fusion proteins in S.
      cerevisiae.
AB  - We have constructed a series of vectors (YGALSETs) for the expression of epitope-
      and affinity-tagged fusion proteins in yeast cells using the regulated GAL10
      promoter. Fusion proteins produced from YGALSET plasmids include a leader peptide
      at the N terminus that encodes both a T7 gene 10 epitope tag and a His6 affinity
      tag. The YGALSET vector series includes centromere plasmids for low-copy plasmid
      maintenance and 2 micron episomal plasmids for multicopy plasmid maintenance and
      four different selectable markers: TRP1, URA3, LEU2 and HIS3. We also provide a
      convenient approach for transferring cloned genes from a bacterial expression
      vector into YGALSET vectors by in vivo recombination and a rapid method to screen
      directly for clones that express the fusion protein of interest.

PMID- 9591128
TI  - UGA read-through artifacts--when popular gene expression systems need a pATCH.
AB  - pET and similar vectors are widely used for efficient gene expression in
      Escherichia coli and subsequent protein purification, often by means of a C
      terminal histidine (His) tag. We found that the TGA translation termination
      signal following the His-tag sequence in pET constructs gives rise to a
      significant fraction of read-through protein extended by 21 amino acids. Mass
      spectrometry indicated that tryptophan is inserted at the UGA (opal) stop codon
      in the examined non-opal suppressor strains; no evidence for translational
      frameshifting was detected. We have shown that the problem of obtaining
      heterogeneous protein preparations can easily be corrected. Plasmid pATCH1
      provides a replacement sequence for the inefficient stop signal and can be used
      to repair both pET vectors and existing pET-based expression constructs. Our
      observation illustrates the largely ignored fact that a UGA codon is the worst
      choice for proper translation termination in efficient overexpression vectors.

PMID- 9591129
TI  - Microsatellite enrichment in organisms with large genomes (Allium cepa L.).
AB  - To exploit the polymorphism of repeat numbers in short tandem repeat (STR)
      sequences (microsatellites) as molecular markers, STRs must be isolated and PCR
      primers must be developed in flanking sequences. In species with large genomes
      such as Allium cepa L. (onion and shallot), an efficient selection procedure for
      genomic fragments containing STRs is a crucial step. Here we describe a
      nonradioactive method for microsatellite isolation based on affinity capture of
      single-stranded restriction fragments annealed to biotinylated microsatellite
      oligonucleotides (CA)10, (GAA)8 and (AAC)8 followed by adapter-mediated genomic
      PCR. Cloning of the products in E. coli and plasmid sequencing revealed more than
      60% positive clones. Primers were designed in STR-flanking regions, and one or
      two bands were amplified in 13 diploid onion and five shallot accessions.
      Allelism of the bands was confirmed by product sequencing.

PMID- 9591130
TI  - Multiwell 14CO2-capture assay for evaluation of substrate oxidation rates of
      cells in culture.
AB  - 14CO2 capture is commonly used to evaluate the cellular oxidation rate of
      respiratory substrates. A modification of the established 14CO2-capture method
      was developed that enables the use of cells in adherent culture and easy analysis
      of multiple samples under different culture conditions. The use of commercially
      available culture and filter plates designed for use in a multiplate
      scintillation spectrophotometer enabled substrate oxidation rates to be evaluated
      for cells in a 24-well plate format without the need to dislodge the cells from
      the culture substrate as is required in traditional methods. Evaluation of
      radioactivity captured in potassium hydroxide-saturated filters was accomplished
      by adding scintillation fluid to the filter plate wells and counting.
      Alternatively, filters could be removed and placed in vials for evaluation in a
      conventional scintillation counter. This method was applied to the oxidation of
      14C-glutamine by human breast cell lines and demonstrated concentration-dependent
      linear accumulation of captured counts.

PMID- 9591131
TI  - Quantitative, competitive PCR assay for HIV-1 using a microplate-based detection
      system.
AB  - We have developed a quantitative competitive PCR (QC-PCR) assay in a microplate
      format for quantifying human immunodeficiency virus Type 1 (HIV-1) DNA or RNA in
      a broad range of source materials. Our QC-PCR assay is a modification of
      technique originally described by Piatak et al. (1993), which is based on the
      presence of a competitive internal standard containing an internal 80-bp deletion
      of HIV-1 gag target sequence. For improved detection and quantification of the
      wild-type and internal-standard PCR products in a microplate format, we
      introduced a non-HIV, 31-bp insert into the internal standard as a probe
      hybridization site that does not cross-hybridize with wild-type HIV-1 products.
      By using a primer pair in which one primer is biotinylated, QC-PCRs can be bound
      to a streptavidin-coated microplate, denatured and probed with a digoxigenin
      (Dig)-labeled, wild-type or internal-standard probe. The hybridized Dig-labeled
      probes are detected with an anti-Dig antibody conjugated to detector molecules
      for luminometry (aequorin) or optical densitometry (peroxidase), yielding results
      that are quantifiable over the range of 100-10,000 copies of HIV gag. Tested
      source materials for HIV-1 DNA or RNA quantification include plasma, vaginal
      lavage and cultured cells. The application of the QC-PCR assay using the
      microplate format affords a convenient and cost-effective method for quantifying
      HIV-1 proviral and viral loads from a variety of body fluids, cells and tissues.

PMID- 9591132
TI  - Fast-painting of human metaphase spreads using a chromosome-specific, repeat
      depleted DNA library probe.
AB  - For chromosome painting, in situ suppression of repetitive DNA sequences has been
      well established. Such standard protocols usually require large amounts of Cot-I
      DNA. Recently, it has become possible to deplete repetitive DNA sequences from
      library probes by magnetic purification and PCR-assisted affinity chromatography.
      These "repeat-depleted library probes" appear to be extremely useful for Fast
      FISH, a technique that omits denaturing chemical agents such as formamide in the
      hybridization buffer, resulting in a substantial acceleration and simplification
      of the complete protocol. Shown here is the application of Fast-FISH to a repeat
      depleted, directly fluorochrome-labeled library probe of the q-arm of chromosome
      15 (Fast-Painting) for human lymphocyte metaphase spreads. Following painting
      without Cot-I DNA and without formamide, visual inspection revealed sufficient
      chromosome painting after a few hours of hybridization. The fluorescence signals
      of the labeling sites were analyzed after hybridization times of 1 and 2 h (in
      one case, 4 h) using digital fluorescence microscopy. The painting efficiency
      expressed in values of relative fluorescence signal ratios was quantitatively
      evaluated by image analysis using line-scan procedures and area-morphometry of
      mean luminance. Two preparation protocols (ethanol dehydration without and with
      RNase A treatment followed by pepsin digestion for four different exposure times)
      were compared. These results indicated that RNase A treatment and pepsin
      digestion are steps that can be omitted.

PMID- 9591134
TI  - High-throughput screening for known mutations by automated analysis of single
      sequencing reactions.
AB  - This work shows that single sequencing reactions analyzed on an automated DNA
      sequencer can be an efficient way of screening PCR products for known mutations.
      We have analyzed a mutation in exon 10 of the human aromatase gene and show that
      an unambiguous genotype could be elucidated in more than 90% of the analyzed
      samples. Compared to analysis by full sequencing, 4 times more samples can be
      analyzed per gel, so that the sample capacity of the gel is approaching that of
      alternative gel-based methods for genotype analysis. Unlike many of these, the
      method offers direct identification of the variant sequence position and on-line
      analysis without the need of post-electrophoretic processing of the gel.

PMID- 9591133
TI  - Quick-FISH: a rapid fluorescence in situ hybridization technique for molecular
      cytogenetic analysis.
AB  - A rapid and simplified fluorescence in situ hybridization (FISH) technique for
      the detection of human chromosome-specific centromeric probes is described. Using
      chromosomes 1-, 4-, 11- and Y-specific fluorescence-labeled probes, the modified,
      or quick-FISH technique, was compared to two conventional FISH methods. The
      modified FISH technique detected human chromosomes without sacrificing
      sensitivity or signal quality in both fresh-frozen and paraffin-embedded tissue
      sections. Further studies demonstrated that this technique can be used with
      simultaneous application of dual-color probes. This novel technique offers the
      advantages of being simpler to perform and faster than conventional techniques.
      The quick-FISH technique can be substituted for any sensitive conventional FISH
      method for molecular cytogenetic analysis in fresh, fresh-frozen or paraffin
      embedded tissues.

PMID- 9591135
TI  - Detection of single-nucleotide polymorphism.

PMID- 9591136
TI  - Doublex sequencing in molecular diagnosis of hereditary diseases.
AB  - We describe doublex sequencing of human genomic PCR products using two
      differently labeled primers in a single reaction and analysis on two automated
      DNA sequencing devices. Feasibility of the methodology is demonstrated by
      isothermal and cycle sequencing for two different PCR products and by cycle
      sequencing on both strands of a single product. It was applied to analyze
      mutations in patient DNAs in routine sample screening. Because it has the
      advantage of increased throughput and cost reduction while retaining its accuracy
      and reading length, we found that doublex sequencing is an attractive option for
      molecular diagnosis of hereditary diseases. This approach would be even more
      beneficial if it used DNA sequencing devices with several lasers in a single
      instrument.

PMID- 9591137
TI  - 3'-end cDNA pool suitable for differential display from a small number of cells.
AB  - We have generated a 3' cDNA pool from the RNA of only 1000 or fewer cells by
      reverse transcription (RT) from an extended oligo(dT) primer with a 3' degenerate
      base and a second strand primer with four degenerate 3' bases, followed by PCR.
      Reproducible differential displays (DD) can be made from this essentially
      inexhaustible source of DNA. The method produced DD patterns that are comparable
      but not identical in band number and size distribution with those obtained by the
      original RT-DD technique. Northern blots performed with the excised bands
      verified altered gene expressions. The data indicate that this 3'-end cDNA pool
      can supplement current PCR-based methods of expression genetics. This pool of
      cDNA sequences also provides a reliable source for primer-specific gene
      amplifications.

PMID- 9591138
TI  - Development of competitive mRNA PCR for the quantification of interleukin-6
      responsive junB oncogene expression.
AB  - The transcription factor junB belongs to the jun family of protooncogenes. The
      appearance of junB mRNA in hepatic cells is an extremely early and sensitive
      marker of the action of proinflammatory cytokines including interleukin-6. In
      this study, a competitive reverse transcription (RT)-PCR assay has been developed
      that is suitable for the quantitative determination of junB mRNA expression. This
      nonisotopic assay compared to other methods (e.g., Northern blot) is a fast and
      convenient way to determine the expression of the junB gene and thus the
      immediate concentration- and time-dependent action of interleukin-6. Because
      interleukin-6 and interleukin-6-type cytokines play a highly important regulatory
      role in various pathophysiologically important processes, such as hepatic acute
      phase reaction, the quantitative assay of junB mRNA completes the scale of
      laboratory approaches in inflammation and among other pathological conditions.

PMID- 9591139
TI  - E. coli-based in vitro transcription/translation: in vivo-specific synthesis
      rates and high yields in a batch system.
AB  - A highly efficient Escherichia coli-based, batch in vitro protein synthesis
      system using circular plasmid DNA is described. Compared to a presently available
      commercial kit, this improved system produced several hundredfold greater yields
      of the rDNA human protein thrombopoietin (ca. 450 micrograms/mL). The system is
      capable of obtaining specific synthesis rates similar to those in vivo,
      approximately a 1000-fold increase compared to the original methods previously
      described. It compares favorably in rates and yields to the recently published
      semicontinuous methods but with the convenience of a true batch system.

PMID- 9591140
TI  - Functional assays to identify and characterize regulators of microtubule
      behavior.
AB  - Previous experiments have clearly demonstrated that microtubule dynamic
      instability is regulated in living cells, but the molecular mechanisms that are
      responsible for this regulation are not well understood. We describe two rapid,
      functional assays that can be used to screen cell extracts for regulators of
      microtubule dynamic instability behavior. In both assays, highly purified tubulin
      is used to assemble microtubules from Tetrahymena axonemes. In the
      immunofluorescence assay, microtubules are visualized by fixation and staining
      with anti-tubulin antibodies. Alternatively, microtubule assembly has been
      visualized by the addition of rhodamine-labeled tubulin to axonemes, followed by
      low-light-level fluorescence microscopy. In either case, polymerization is
      quantified by measuring polymer length, total polymer and the number of
      microtubules per axoneme. In these assays, addition of brain microtubule
      associated proteins (MAPs) results in a 2-fold-3-fold increase in average
      microtubule length, and addition of vinblastine results in a 50%-75% decrease in
      average microtubule length. The number of microtubules per axoneme was
      significantly increased by the addition of MAPs and significantly decreased by
      the addition of vinblastine. These functional assays can detect molecules that
      stimulate or suppress net microtubule assembly and provide a useful initial
      screen to isolate regulators of microtubule dynamic behavior.

PMID- 9591141
TI  - Sexual adjustment and its predictors after traumatic brain injury.
AB  - The aim of this study was to investigate the impact of traumatic brain injury
      (TBI) on sexual ability, activity and satisfaction and to relate the findings to
      neurological status, functioning and well-being. A total of 92 TBI persons (65
      men, 27 women) participated. Their ages ranged from 20-70 years (median 40
      years); the median age at injury was 32 years, ranging from 16-56 years. The
      elapsed time since injury ranged from 1-20 years (median 9 years). The
      participants were examined according to a procedure including neurological
      examination, self-assessment of general health status and functioning and mood,
      and collection of data on social conditions. A structured study-specific
      questionnaire was developed to assess various aspects of sexuality before and
      after the injury. Fifty-three of the participants had a stable partner
      relationship at the time of the investigation. This study showed that a TBI
      commonly alters sexual functioning as well as desire. Many of the respondents
      reported decreased ability to achieve an erection, decreased ability to
      experience organism, decreased sexual desire and diminished frequency of
      intercourse. A high degree of physical independence and maintained sexual ability
      were the most important predictors for sexual adjustment. Considering that many
      TBI persons in this study reported physiological sexual disturbances and
      decreased sexual ability, it is important to inform patients about possibilities
      of optimizing their sexual ability. Organized programmes of sexuality education
      should be an integral component of TBI rehabilitation.

PMID- 9591142
TI  - Cognitive-linguistic subgroups in closed-head injury.
AB  - This study examined variability in the interrelationship between language skill
      and neuropsychological function within a group of 25 severe closed head injury
      (CHI) subjects and 23 matched controls. All subjects underwent a battery of
      standardized language and neuropsychological tests. Cluster analyses were
      conducted to determine whether the CHI sample was universally or differentially
      impaired. Further subgroup analysis using a Q-type factor analysis outlined the
      differences in performance profiles within the group of CHI subjects. Results
      support the hypothesis that while some deficits were common to all CHI subjects,
      impairments delineated by whole group analysis do not necessarily represent
      universal impairments. In particular, ability to perform tasks involving auditory
      comprehension, naming, verbal memory, visual memory and visuospatial skills
      appeared to be important components in group differentiation. The cognitive
      linguistic impairments which were common to all CHI subjects and considered to be
      the 'cardinal' cognitive-linguistic deficits following severe CHI were deficits
      in lexical-semantic and sentential semantic skills, verbal fluency, complex
      auditory comprehension, and attentional operations. Profile analysis revealed the
      existence of a double dissociation between performances on naming and verbal
      memory tasks and performances on visually related cognitive tasks. Results are
      discussed with reference to findings on previous studies of subgroups in the CHI
      population.

PMID- 9591143
TI  - The Lighthouse Strategy: use of a visual imagery technique to treat visual
      inattention in stroke patients.
AB  - Eight male and eight female stroke patients, aged 45-77, were asked to imagine
      their eyes as horizon-sweeping beams of a lighthouse and were then cued to use
      this image in functional and therapy training tasks as part of their treatment
      for visual inattention within a comprehensive day rehabilitation programme.
      Treatment Group patients' performance on the Mesulam Verbal Cancellation Test
      given at admission and discharge were significantly improved (p = 0.002). In
      comparison with controls matched for diagnoses, race and age, significant
      improvement (p = 0.007, f = 8.389) also occurred by discharge in the overall
      attention of patients taught to use the 'Lighthouse Strategy' as measured by a
      facility rating scale and reports by family and caregivers. Further potential
      applications of visual imagery to the retraining of compensatory cognitive and
      other skills are discussed.

PMID- 9591144
TI  - Morphological astrocytic changes in complicated human brain trauma. A light and
      electron microscopic study.
AB  - The astrocytic changes and reactivity in human brain trauma complicated with
      subdural haematoma or hygroma have been analysed in nine patients. Cortical
      biopsies of frontal, temporal and parietal regions were examined with light and
      transmission electron microscopy. At light microscopy level oedematous clear and
      dense astrocytes, binucleated and multinucleated astrocytes and hypertrophic
      reactive astrocytes were distinguished in either moderate or severe vasogenic
      brain oedema. Swollen, clear and dense perineuronal astrocytes were observed
      compressing and indenting dark, degenerated pyramidal and non-pyramidal nerve
      cells. At electron microscopy level glycogen-depleted and glycogen-rich
      astrocytes were found in some patients. Dense and reactive hypertrophic
      astrocytes exhibited increased amounts of dilated smooth endoplasmic reticulum,
      microtubules, lipofucsin granules, gliofilaments and alpha type glycogen
      particles. In severe oedema the astrocytic ensheathment of synaptic contacts is
      lost, the perivascular astrocyte end-feet appeared dissociated from the capillary
      basement membrane and the interastrocytary gap junctions are disrupted. The
      posttraumatic neurological deficits and the neurobehavioural disorders of the
      patient studied are correlated with astrocyte ultrastructural changes and blood
      brain barrier disruption.

PMID- 9591145
TI  - Bradykinesia and bradyphrenia revisited: patterns of subclinical deficit in motor
      speed and cognitive functioning in head-injured patients with good recovery.
AB  - Twenty-four patients, showing a good clinical recovery from coma-inducing injury
      and coping well with the activities of everyday living, were tested, at least 1
      year after trauma, on motor speed and reaction time, and given a
      neuropsychological examination. While the patients generally performed within the
      normal range on the neuropsychological tests, their motor speeds and reaction
      times--both simple (SRT) and complex (CRT)--were significantly slower than those
      of matched controls. This points to a subclinical bradykinesia. The patients'
      motor speed scores did not correlate significantly with any of the
      neuropsychological tests; nor did SRT or CRT. While the difference between simple
      and complex reaction time was significantly greater in the patient group, the
      percentage difference was not significantly different between the two groups.
      Collectively, these results suggest that bradykinesia and bradyphrenia do not
      necessarily overlap. Finally, there was no significant correlation between motor
      performance and severity of original injury, whether the latter was measured by
      number and size of lesions or by duration of post-traumatic amnesia.

PMID- 9591147
TI  - Cholelithiasis and fitness for work at sea.
AB  - The aim of the present study was to investigate the occurrence of cholelithiasis
      in the occupationally active population of seamen and deep-sea fishermen aged 20
      60, to assess the impact of environmental and dietary factors upon its course and
      to evaluate the fitness for work at sea of persons with biliary stones. The study
      group comprised 36 seamen and fishermen who received surgical treatment because
      of symptoms and complications of cholelithiasis, and 1000 seamen and fishermen
      periodically examined among whom 34 cases of asymptomatic cholelithiasis were
      diagnosed. The diagnosis was based on the anamnesis, physical examination and usg
      examination of the gallbladder and biliary ducts, in selected cases supplemented
      by other examinations. It was demonstrated that the factors which are concomitant
      and stimulate the development of biliary stones in seamen and fishermen were
      obesity and alcoholism. No role of hyperlipidemia and the type of diet in the
      formation of biliary stones was confirmed. In the group of 36 patients, the
      indications for the surgical treatment were complications of choletithiasis, i.e.
      biliary duct stones, mechanical jaundice, acute hydrops or empyema of the
      gallbladder. They resulted in temporary unfitness for work at sea. Asymptomatic
      cholelithiasis in seamen and fishermen does not result in unfitness for work at
      sea and is not an indication for surgical treatment.

PMID- 9591146
TI  - Comparative study of the death during sea voyages among Polish seamen and deep
      sea and boat fishermen.
AB  - 181 fatal cases of diseases and work-related accidents recorded in the years 1985
      1994 among seamen and fishermen were analyzed. The highest mortality rate and
      fatal accident rate were noted in seamen. They were higher than those pertaining
      to workers employed on land. The respective rates for Polish fishermen were lower
      than those reported in other countries. The main causes of death at sea were sea
      catastrophes, injuries, drowning, poisoning and circulatory system diseases. The
      most frequent were deaths during the day and not on the watch, being alone in the
      cabin. Limited access to qualified medical assistance during the voyage and
      frequent occurrence of sudden deaths reduce substantially the efficacy of help.
      Therefore, prevention of diseases and accidents is of crucial importance.

PMID- 9591148
TI  - State of the circulatory system in stevedores.
AB  - Examinations on stevedores were performed in three series in the period from 1976
      to 1997. Randomly selected were 286 of them in the first series of examinations,
      224 in the second and 106 in the third one. In addition, the examinations
      enrolled also 106 stevedores who have lost their health qualifications, 55
      retired workers, and 363 harbour workers whose jobs did not include direct
      loading of cargo, and they constituted the control group. Cardiographic
      examinations were performed in the morning, ECG was carried out with the use of
      Multiscriptor apparatus and the evaluation was made using the Minnesota code.
      Systolic blood pressure in stevedores averaged: 124.6 +/- 14.9 mm Hg in the first
      series, 123.8 +/- 18.9 mm Hg in the second, and 127.5 +/- 16.7 mm Hg in the third
      series; it was 125.9 +/- 14.0 mm Hg in the retired stevedores, and 134.0 +/- 17.0
      mm Hg in the control group. Electrocardiographic sings of the left heart
      hypertrophy were found in: 32.2%, 30.3%, 29.2%, 23.1% and 11.0% of the examined
      groups, respectively. Traits of the effect of the parasympathetic system in the
      ECG according to clinical criteria were recorded in: 58.7% of subjects in the
      first series, 54.5% in the second, 51.9% in the third, 42.6% in the retired
      stevedores, and 6.9% in the control group. The systolic pressure of 120 mm Hg and
      less in the newly employed stevedores was recorded in less than 7.5% of examined
      subjects. In 9.2% cases a syndrome of early repolarization of heart ventricles
      was noted. Hypervagotony is characteristic for the stevedores with a long period
      of work. Evaluating their state of the circulatory system, a pronounced
      beneficial effect of an intense physical activity can be observed.

PMID- 9591149
TI  - Cervical and back pain syndrome in port workers.
AB  - The surveyed group consisted of 338 port workers including 136 stevedores, 128
      operators of mechanized equipment and 74 hoistmen. 233 people (68.9%) complained
      of cervical and back pain. In relation to the size of the groups examined, the
      pain was reported by 84.6% stevedores, 60.8% hoistmen and 57.0% operators. On the
      basis of the clinical course, the types of the pains were determined in
      stevedores to be: skeletogenic--in 41.8% of them, neurogenic--25.4%, angiogenic-
      4.5% and mixed within the cervical segment of the spine--28.3%. The back pain in
      the group of stevedores was classified as high ischialgia--in 65.7%, low
      ischialgia--in 24.6% and lumbar pain and sacralgia--in 9.7% of cases. In hoistmen
      and operators, lumbagia and sacralgia were two times more frequent than in
      stevedores. Sick leave in the subjects examined in the course of the seven-year
      observation totalled 18,452 days, in that number 7646 days in connection with
      diseases of the muscular-skeletal system, and 5150 days by problem in the spine.
      In operators and hoistmen the absence caused by these diseases was proportionally
      two times lower than in stevedores.

PMID- 9591151
TI  - Accidents and injuries in Polish seafarers.
AB  - A survey was conducted among Polish seafarers on work-related accidents and
      injuries. Their average incidence rate in 1990-1995 was 22.07 per 1000 men per
      year (fatal accidents: 0.85/1000). Out of 960 accidents recorded including 37
      fatal ones, 768 caused work incapacity, and in 307 major injuries the duration of
      it was 29 or more days. The causes of death of seafarers were: drowning 24,
      violence 2, suffocation 4, contusion 2, and disappearance from ship during voyage
      5. The incidence rate of accidents in the surveyed population varied from year to
      year and there was no tendency of lowering it. Prevention of accidents on ships
      should be improved.

PMID- 9591150
TI  - Diseases and work-related injuries in Polish seafarers and conditions of their
      work on foreign-flag ships.
AB  - A questionnaire survey was conducted in 1994-1996 among Polish seafarers employed
      on foreign-flag ships, in order to collect their opinions and experiences on work
      and life on these ships, and to estimate the morbidity and injuries incidence.
      The majority of 1103 respondents were satisfied with the conditions of work and
      life on these ships: their food, accommodation, the health and safety of work,
      standard of health care on board were good or satisfactory; they had no problems
      with living and working together on the same ship with seamen of other
      nationalities. But about 7.8% of respondents complained that the safety and
      health of work on their ship was unsatisfactory, or conditions of work
      "endangered their health and life". The self-reported morbidity (calculated rate
      176.8 per 1000 men per year) and accidents (rate 114.5 per 1000 per year) was
      recorded.

PMID- 9591152
TI  - Effect of saturated air and nitrox diving on selected parameters of haemostasis.
AB  - The objective of the study was to evaluate decompression stress after air and
      nitrox saturated divings on the basis of the parameters of haemostasis. Before
      and after each diving the following examinations were performed: blood platelet
      count, aggregation, fibrinogen level and coagulation factors VII, X and XII.
      After the air saturated dives a slight reduction of factor X and XII and of
      fibrinogen was observed. Evaluation of haemostatis may be one of the basic
      elements in the assessment of decompression sickness risk.

PMID- 9591153
TI  - Yperite burns in Polish fishermen.

PMID- 9591154
TI  - Xylitol for messrooms--a method worth trying to prevent caries among seafarers.
AB  - Oral diseases seem to be the most common health problem of seafarers world-wide.
      Seafaring as an occupation may create a risk for the dental health of crews of
      ships. Sitting in messrooms and eating snacks in between regular meals is a
      popular way of spending free time during the ships voyage. This means not only
      high caloric intake which contributes to overweight but also to high dental
      caries incidence among crews. During long sea voyages, the access of seamen to
      dental services is very limited and making regular check ups and treatment of
      caries is difficult. The best solution to the problem of poor teeth is a
      preventive one. Conventional methods for preventing caries are health education,
      restrictions the use of sugar-containing products, good oral hygiene and use of
      fluorides. A newer method to prevent caries is systematic use of xylitol.
      Scientific evidence shows that the addition of small quantities of xylitol, a
      natural carbohydrate sweetener, to the diet causes a significant reduction in the
      incidence of dental caries.

PMID- 9591155
TI  - Malaria in India and advice on its prevention among seafarers coming to Calcutta
      and other ports in the country.

PMID- 9591156
TI  - Occupational and environmental medicine in the United States.
AB  - The history and the current status of occupational and environmental medicine
      (OEM) research, educational resources, clinical practice patterns, and regulatory
      framework in the United States are reviewed. Current or anticipated changes in
      health-care financing, clinical practice patterns, occupational safety and health
      regulations and enforcement, and funding for research and medical education at
      the national level are already having an impact on OEM activities in this
      country.

PMID- 9591157
TI  - Urinary cotinine as a tobacco-smoke exposure index: a minireview.
AB  - A minireview is presented concerning the use of cotinine as a tobacco-smoke
      exposure index. First, general considerations about methods for the determination
      of urinary cotinine are presented. Besides pure analytical aspects, this
      minireview considers major problems encountered in the establishment of threshold
      values that can be used to distinguish not only smokers from nonsmokers but also
      nonsmokers exposed or not exposed to environmental tobacco smoke (ETS). In
      addition, the use of urinary cotinine is illustrated in several situations where
      smoking status assessment is of interest. Such situations include evaluation of
      the impact of smoking cessation programs, monitoring of pregnancy and of other
      groups at risk, assessment of occupational exposure to industrial pollutants,
      validation of phase I clinical trials, and the control of life insurance
      candidates. The specific problem of ETS exposure assessment is briefly mentioned.

PMID- 9591158
TI  - An epidemiology study of lung function changes of toluene diisocyanate foam
      workers in the United Kingdom.
AB  - OBJECTIVE: To determine whether longitudinal declines in ventilatory capacity and
      the occurrence of respiratory symptoms in workers manufacturing polyurethane foam
      were related to toluene diisocyanate (TDI) exposure. METHODS: A population of 780
      workers in 12 United Kingdom factories was followed for 5 years. Modified United
      Kingdom Medical Research Council (MRC) respiratory questionnaires and three or
      more lung function measurements were completed for each subject. Mean TDI
      exposures for all jobs in which subjects were employed were assessed by personal
      monitoring (2294 measurements) and related to their occupational histories.
      RESULTS: The United Kingdom 8-h and 15-min maximum exposure limits for TDI were
      exceeded in 4.7% and 19.0% of the samples taken, respectively. There was some
      increase in reported respiratory symptoms amongst exposed workers, but the annual
      declines of 1-s forced expiratory volume (FEV1) and forced vital capacity (FVC)
      were not related to TDI exposure and were typical of those observed in other
      longitudinal populations. FEV1 declines were smoking-related. Evidence was found
      suggesting that a small excess decline in FEV1 and FVC occurred in the first few
      years of employment for workers not previously exposed to TDI. CONCLUSION: This
      study does not provide evidence that there is a TDI-related decline in FEV1 and
      FVC in workers exposed to less than the United Kingdom 8-h occupational exposure
      limit of 5.8 ppb.

PMID- 9591159
TI  - Exposure to lead and other metals in children from Katowice district, Poland.
AB  - OBJECTIVES: To assess the exposure to toxic metals and to evaluate its possible
      association with essential elements and socioeconomic status in children from the
      town of Bytom in the Katowice area; this area is one of the most polluted
      industrialized regions in Poland. METHODS: Concentrations of lead, cadmium,
      mercury, selenium, magnesium, copper, and zinc were determined in whole blood of
      211 children aged 9 years. The samples were analyzed using inductively coupled
      plasma mass spectrometry (ICP-MS). Information on socioeconomic factors was
      collected using questionnaires. Concentrations of trace elements in the blood of
      24 Swedish children aged 9-10 years were used for comparisons. RESULTS: The
      concentrations of lead detected in the blood of the Polish children ranged from
      0.09 to 1.9 mumol/l, with the median value being 0.27 mumol/l. Statistically
      significant associations were found between lead and such socioeconomic factors
      as the number of siblings, trips outside the region, maternal smoking, playing
      outdoors, and apartment standard. The average blood lead level was about 3 times
      higher in the Polish children than in the Swedish group. The median blood
      concentration of cadmium found in the Polish children was 3.4 nmol/l (range 1.1
      41 nmol/l; almost 3 times higher than that detected in the Swedish children), and
      that of mercury was 3 nmol/l (range 0.5-11 nmol/l). The median blood levels and
      ranges of the essential elements were 1.1 (0.7-2.0) mumol/l for selenium, 1.5
      (1.2-1.9) mmol/l for magnesium, 17 (13-22) mumol/l for copper, and 78 (54-104)
      mumol/l for zinc, respectively. The concentrations of selenium and magnesium were
      significantly lower in the Polish group as compared with the Swedish children.
      CONCLUSIONS: In all, 7% of the Polish children had blood lead levels exceeding
      0.5 mumol/l, the concentration above which negative effects on mental development
      have been reported. However, the findings indicate a decrease in lead exposure
      during recent years among the Bytom children.

PMID- 9591160
TI  - Cancer incidence among Finnish workers exposed to aromatic hydrocarbons.
AB  - OBJECTIVES: To assess whether occupational exposure to aromatic hydrocarbons
      increases carcinogenic risk. METHODS: We followed cancer incidence among 3,922
      male and 1,379 female workers monitored for exposure to styrene, toluene, or
      xylene. The follow-up after the first personal measurement comprised 66,500
      person-years at risk over the period 1973-1992. We computed the indirectly
      standardized incidence ratios (SIR) with 95% confidence interval (CI) with regard
      to age-, gender-, and period-specific incidence rates of cancer in the Finnish
      general population. RESULTS: The overall rate of cancer incidence for the total
      cohort was fairly similar to that of the general population. The risk for nervous
      system tumors was increased at 10 years after the first personal measurement (SIR
      2.80, CI 1.03-6.08). For styrene there was an excess risk for rectal cancer (SIR
      3.11, CI 1.14-6.77), and risks for pancreatic and nervous system tumors were
      increased nonsignificantly. For toluene and xylene, no clear increase in cancer
      risk was found. CONCLUSIONS: The data are not supportive of an overall increase
      in the cancer risk for these solvents, even though we cannot rule out site
      specific associations with the rectum, pancreas, and nervous system. There is
      supporting evidence in the epidemiology literature for pancreatic cancer risk and
      heavy exposure to styrene. More studies are warranted on solvents, with detailed
      information on lifetime exposures and habits being collected whenever possible.

PMID- 9591161
TI  - Qualitative color vision impairment in toluene-exposed workers.
AB  - OBJECTIVE: The aim of this study was to evaluate whether toluene, like many other
      organic solvents and solvent mixtures, could impair color vision. SUBJECTS AND
      METHODS: We investigated color vision impairment in three groups of workers, two
      groups occupationally exposed to toluene and a nonexposed group. The first
      exposed group, group E1, comprised 41 workers (median value of toluene in air
      35.00 ppm, range 11.3-49.3 ppm) and the second exposed group, group E2, comprised
      32 subjects (median value of toluene in air 156.00 ppm, range 66.0-250.0 ppm).
      The nonexposed group, group NE, comprised 83 subjects. Color vision was evaluated
      by the Lanthony D-15 desaturated test according to Verriest's classification:
      type I, loss in the red-green range; type II, loss in the blue-yellow and red
      green ranges, and type III, loss in the blue-yellow range. Subjects were
      classified as dyschromates if specific acquired loss was determined in at least
      one eye. In both exposed groups, exposure was evaluated by measurement of the
      concentration of toluene in the ambient air and in the blood. In group E2, level
      of hippuric acid and orthocresol in urine after the work shift were also
      determined. The Mann-Whitney U-test, t-test, chi 2-test, and Spearman's rank
      correlation and multiple regression analysis were used for statistical analysis.
      RESULTS: Type III dyschromatopsia was detected in all groups examined: 26.6% of
      the workers in group NE, 31.7% of those in group E1, and 50% of those in group
      E2. As many as 15.6% of the workers in group E2, 4.8% of those in group E1, and
      only 1.2% of those in group NE had type II dyschromatopsia. A statistically
      significant difference in the prevalence of total dyschromatopsia (type III +
      type II) was established among the three examined groups together (chi 2 = 14.13;
      df = 2; P < 0.01), between group E2 and group E1 (chi 2 = 4.96; P < 0.05), and
      between group E2 and group NE (chi 2 = 12.50; P < 0.005), whereas no significant
      difference was found between groups E1 and NE. Type III dyschromatopsia was
      significantly correlated with age in group NE (P < 0.01) and in group E1 (P <
      0.005). In group E2, both type II (P < 0.05) and type III dyschromatopsia
      correlated with toluene in ambient air and with the duration of exposure to
      toluene (both P < 0.005). In group E2, total dyschromatopsia correlated
      significantly with toluene in ambient air and in blood (both P < 0.05) as well as
      with hippuric acid in urine after the work shift (P < 0.001). CONCLUSION: This
      study suggests that toluene can impair color vision.

PMID- 9591162
TI  - Measured exposures by personal monitoring for respirable suspended particles and
      environmental tobacco smoke of housewives and office workers resident in Bremen,
      Germany.
AB  - OBJECTIVE: Exposures to respirable suspended particles (RSP) and environmental
      tobacco smoke (ETS) were assessed in Bremen, Germany, as part of a European air
      quality study. The range and level of personal exposures were assessed for
      housewives and office workers. DESIGN: Nonsmokers were randomly selected from a
      representative sample of the population of Bremen. Housewives were recruited into
      one group primarily for assessment of exposures in the home and office workers,
      into a second group for assessment of the contribution of the workplace to
      overall exposure. METHODS: A total of 190 subjects collected air samples from
      areas close to their breathing zone by wearing personal monitors for 24 h.
      Samples collected were analysed for RSP, ultraviolet-absorbing particulate matter
      (UVPM), fluorescing particulate matter (FPM), solanesol-related particulate
      matter (SolPM), nicotine and 3-ethenylpyridine (3-EP). Saliva cotinine levels for
      all subjects were also established. RESULTS: Overall the levels found were quite
      low, with the majority of results being below the limit of quantification.
      Workers both living and working with smokers were exposed to the highest 24-h
      median quantities of RSP (789 micrograms) and ETS particles (128 micrograms)
      measured by FPM. The highest nicotine levels, based on median 24-h time-weighted
      average concentrations, were experienced by office workers working with smokers
      (0.69 microgram m-3). These workers were also found to have the highest median
      cotinine levels (1.6 ng ml-1). CONCLUSIONS: The most highly exposed workers, both
      living and working with smokers, would potentially inhale over 20 cigarette
      equivalents (CE) per annum as based on the upper decile levels. Housewives living
      with smokers could inhale up to 11 CE per annum as based on the upper decile
      levels. Locations outside the workplace, including the home, contribute most to
      overall RSP and ETS particle exposure. Consideration should be given to extending
      the personal monitoring period in cities where levels appear to be quite low.

PMID- 9591163
TI  - Chromosome analysis of lymphocytes from radiation workers in tritium-applying
      industry.
AB  - OBJECTIVES: The frequency of chromosomal aberrations (CA) and micronuclei (MN) in
      peripheral blood lymphocytes was compared in two groups of persons occupationally
      exposed to tritium either through the use of luminous paints or in the weapons
      industry, with the aim of finding a correlation between the CA and MN assays, the
      extent of radiation hazard, and the duration of occupational exposure to chemical
      forms of tritium and the ability of the latter to induce hazards in human
      lymphocytes. METHODS: CA analysis and the cytochalasin B micronucleus test were
      performed. Urinary tritium in both groups was measured using a liquid
      scintillation method. For purposes of comparison, 2 control groups (40 persons)
      were examined; 24 exposed individuals were matched to their controls according to
      age, sex, and smoking habits. RESULTS: Values recorded for the frequency of CA in
      the group of workers handling tritium in luminous dial painting were 0.015 +/-
      0.014 dicentrics/cell, 0.023 +/- 0.017 total unstable CA/cell, and 0.035 +/-
      0.019 MN/binucleated cell. Urinary levels of tritium in this group of employees
      ranged from 1.35 to 9.43 MBq/l. As compared with their matched controls, in these
      workers the differences in the yield of CA as well as in MN were statistically
      highly significant (P < 0.005 and P < 0.003, respectively). The same parameters
      analyzed in workers employed in the armament industry gave values of 0.001 +/-
      0.003 dicentrics/cell, 0.010 +/- 0.008 total unstable CA/cell, and 0.021 +/-
      0.029 MN/binucleated cell. No detectable concentration of urinary tritium was
      found. As compared with their matched controls, in these workers the differences
      were also statistically significant (P < 0.027 and P < 0.012, respectively). The
      yield of CA, particularly the yield of dicentrics, was significantly higher (P <
      0.005) in the group of luminous dial painters as compared with the weapons
      industry workers. The difference found in the yield of MN between the two groups
      of workers was also statistically significant (P < 0.084). Intercontrol
      differences in the yields of spontaneous CA as well as in MN were insignificant
      (P < 0.683 and P < 0.735, respectively). The results are discussed with respect
      to individual variations in the response to low doses of ionizing radiation,
      disorders in the handling of radionuclides, the duration of occupational
      exposure, and the chemical properties of the radionuclides used. CONCLUSION:
      Tritium in the chemical form of luminous paint is a more powerful clastogenic
      agent than tritium gas. Statistical analysis demonstrated that lymphocyte effects
      are due to the concentration of tritium in urine rather than to the duration of
      occupational exposure. Since the radiation hazard measured by the MN assay did
      not differ from that determined by the CA assay, the MN test can be recommended
      as a rapid assay for screening purposes in cases of occupational exposure to low
      radiation doses.

PMID- 9591164
TI  - Human biomonitoring of antimony.
AB  - OBJECTIVES: The aim of the study was to test the suitability of 24-h urine,
      blood, and scalp-hair samples as surrogates for the determination of internal
      exposure to antimony in case of a strongly elevated soil contamination with
      antimony. METHODS: The bio-monitoring was performed using graphite-furnace atomic
      absorption spectrometry. Blood and scalp-hair samples were decomposed by
      microwave digestion. RESULTS: No elevated content of antimony could be detected
      in 24-h urine, blood, or scalp-hair samples from the study participants
      geogenically exposed to antimony. The results did not show a correlation between
      the antimony contents in the soil of the housing area and those in urine, blood,
      or hair. Surprisingly, the reference group (n = 47) showed a significantly higher
      median antimony excretion rate than did the exposed group (n = 89; 1.23 versus
      0.60 micrograms Sb/24 h). Additionally, the scalp-hair contents of the reference
      group were also significantly higher than those of the exposed persons (0.045
      versus 0.026 mg Sb/kg). Blood contents of the two study groups were 0.57 and 0.48
      microgram Sb/l, respectively. The detection limit for urine and blood was 0.5
      microgram Sb/l and that for scalp hair was 0.005 mg Sb/kg. Of all samples of
      urine, blood, and scalp hair analyzed, 31.2%, 49.3%, and 10.3%, respectively,
      were below the limit of analytical detection. CONCLUSIONS: The antimony contents
      recorded for both study groups in urine, blood, and scalp hair can be judged as
      being within the normal range. The rate of transfer of antimony from the soil to
      humans in the exposure case described seemed to be very low. With respect to
      analytical practicability and validity, urine was the surrogate which deemed most
      useful for determination of internal exposure to antimony.

PMID- 9591165
TI  - Influence of positive life events on blood pressure in adolescents.
AB  - It has been reported that adults suffering from refractory essential hypertension
      experience significantly fewer positive life events than healthy peers. However,
      the influence of positive life events on blood pressure (BP) in adolescents has
      been largely ignored. Therefore, we examined the relationship between self
      reported positive life events and BP in 69 sixth graders with a mean age of 11.7
      years. Positive life events were assessed with the Adolescent Perceived Events
      Scale and resting blood pressure was measured with a mercurial sphygmomanometer.
      Correlational analyses showed an inverse relationship between positive life
      events and diastolic BP, suggesting that adolescents experiencing more positive
      life events were more likely to have lower diastolic BP's. Hierarchical
      regression analyses revealed that physical activity level, dietary sodium-to
      potassium ratio, parental history of hypertension, and measures of body
      composition predicted 24.6% of the variance in systolic BP and 34.6% of the
      variance in diastolic BP. Moreover, positive life events predicted an additional
      4.3% of the variance in diastolic BP when statistically controlling these
      established risk factors for hypertension. These results suggest that increased
      perceptions of positive life events may act as a buffer to elevated BP in
      adolescents.

PMID- 9591166
TI  - Cognitive predictors of depression in chronic low back pain: toward an inclusive
      model.
AB  - Previous research has linked cognitive distortion, perceived interference with
      instrumental activities, and self-control to depression in chronic pain patients,
      though to date no study has examined all three variables concurrently. The
      present study investigated these three cognitive mediators in a comprehensive
      model to determine whether each variable represented an independent dimension in
      the pain-depression relationship. Results in a sample of 74 chronic low back pain
      patients revealed that a regression model containing all three cognitive
      variables had the strongest association with depressive symptoms. Consistent with
      a cognitive mediational model of the pain-depression relation, when self-control,
      cognitive distortion, and interference were held constant, pain and disability
      did not have a significant association with self-reported depression. These
      findings indicate that a comprehensive cognitive model of depression and chronic
      pain will need to incorporate all three cognitive variables.

PMID- 9591167
TI  - Defensive coping in relation to casual blood pressure and self-reported daily
      hassles and life events.
AB  - Our aim was to investigate the relationships between defensiveness and
      repression, on the one hand, and self-reported stressor exposure and resting
      blood pressure, on the other hand. In addition, different operationalizations of
      defensiveness and repression were compared. Participants were 310 male and 90
      female employees representing a wide range of occupations. Before a medical
      examination, all subjects completed questionnaires measuring defensiveness,
      anxiety, repression, daily hassles, and life events. After controlling for
      potentially confounding variables, multiple regression analyses revealed an
      inverse association between defensiveness and self-reported number of daily
      hassles and a positive link between defensiveness and resting systolic blood
      pressure. In general, the interaction between defensiveness and anxiety
      (representing repression) did not add to the predictive power of defensiveness
      and anxiety alone. The results support the notion that defensive individuals tend
      to underreport problems, while exhibiting elevated resting blood pressures.

PMID- 9591168
TI  - Evaluation of multimodal treatment program for fibromyalgia.
AB  - A quasi-experimental design was used to assess a multimodal pain treatment
      program for female patients with fibromyalgia to ascertain immediate and long
      term effects. Laboratory and self-report pain measures together with
      psychological measures were obtained from patients who were tested up to 6 months
      after treatment. Comparison data were also obtained from fibromyalgia patients
      who failed to qualify for the treatment program because of insurance coverage.
      Immediate and long-term treatment effects were evident with the psychological
      measures and the subjective pain measures but not with the laboratory pain
      measures. Participants who attended the month-long multimodal program achieved
      significant and positive changes on most of the outcome measures. However,
      relapse prevention must be addressed.

PMID- 9591169
TI  - The Pediatric Cancer Quality of Life Inventory (PCQL). I. Instrument development,
      descriptive statistics, and cross-informant variance.
AB  - Intensive antineoplastic treatment protocols have been developed and implemented
      in controlled clinical trials with the goal of improving the survival of
      pediatric cancer patients. Multidimensional health outcome evaluation of this
      cohort of pediatric cancer patients being treated with these modern regimens is
      essential in order to enhance health-related quality of life. The Pediatric
      Cancer Quality of Life Inventory (PCQL) was developed to be a standardized
      assessment instrument to assess systematically pediatric cancer patient's health
      related quality of life outcomes. The PCQL was administered to 291 pediatric
      cancer patients and their parents at various stages of treatment. The aim of the
      present study was to present the development, descriptive statistics, and cross
      informant variance for the PCQL items. Large variability in symptoms and health
      related problems were found as expected given the wide heterogeneity in the
      patient population sampled. Patient/parent concordance on individual items
      averaged in the medium effect size range. The findings underscore the importance
      of measuring both patient report and parent report of patient symptoms and
      problems in pediatric cancer health-related quality of life assessment.

PMID- 9591170
TI  - State anxiety following resistance exercise: the role of gender and exercise
      intensity.
AB  - Two experiments were conducted to investigate the effect of resistance exercise
      on state anxiety. In experiment 1, participants engaged in three 20-min bouts of
      resistance exercise, with intensity set as a function of perceived exertion.
      Results indicated that the relationship between resistance exercise and anxiety
      was moderated by both exercise intensity and gender. Although females reported no
      change in anxiety, males reported an increase in anxiety following moderate- and
      high-intensity exercise, and a decrease in anxiety following low intensity
      exercise. Experiment 2 was designed to replicate these findings utilizing a more
      precise manipulation of exercise intensity. Results indicated that the change in
      anxiety was again moderated by exercise intensity but was unaffected by gender.
      Both males and females reported increases in anxiety following 20 min of high
      intensity exercise (75-85% of 1 RM), as well as significant decreases in anxiety
      following low-intensity exercise (40-50% of 1 RM).

PMID- 9591171
TI  - The CarboMedics prosthetic heart valve in the mitral position: results of the
      multicenter international trial.
AB  - Isolated mitral valve replacement using the CarboMedics prosthetic mitral valve
      (CarboMedics, Inc., Austin, TX) was studied in 13 centers in the United States,
      Canada, and Scandinavia between 1987 and 1993 in 428 patients with a mean age of
      57 +/- 14 years. Actuarial survivals at 1, 2, and 5 years were 88.2% and 75.8%.
      Freedom from events at 5 years were 94.8% for major thromboembolism, 96.6% for
      thrombosis, and 96.7% for endocarditis. Linearized morbidity rates (events per
      100 patient years) for events at > 30 days postoperatively were .51 thrombosis,
      1.1 major thromboembolism, and .37 endocarditis. These results at early to mid
      term compare favorably with the first generation bileaflet valve.

PMID- 9591173
TI  - Techniques for retrograde cerebral perfusion in the treatment of aortic lesions
      via left thoracotomy.
AB  - Retrograde cerebral perfusion under deep hypothermic circulatory arrest is a
      simple and useful adjunct in aortic surgery and is performed by many surgeons in
      the treatment of aortic arch pathology. In recent years, this technique has been
      recommended in the surgery of distal arch and proximal descending aortic lesions
      through a left thoracotomy inclusion. The aim of the technique is to increase the
      right atrial pressure for retrograde cerebral perfusion. After cooling using
      femorofemoral bypass, circulatory arrest is initiated. The right atrial pressure
      is increased to 20 mmHg, and retrograde cerebral circulation results. In this
      article, five patients with distal aortic arch and proximal descending thoracic
      aortic lesions who were operated on by using this technique were evaluated. It is
      suggested that this technique can be used with a lateral thoracotomy approach
      that is suitable for procedures on a distal aortic arch and proximal descending
      aorta.

PMID- 9591172
TI  - Reoperations with the right gastroepiploic artery without cardiopulmonary bypass.
AB  - The right gastroepiploic artery (RGEA) has been utilized as the bypass conduit on
      the inferior surface of the heart with a minimally invasive approach. Fourteen
      patients had reoperative coronary bypass surgery for severely symptomatic single
      vessel disease of the right coronary artery. All surgeries were performed since
      May 1996. A small mid-line incision including splitting of the lower sternum gave
      excellent exposure. The inferior surface of the heart was dissected to expose and
      stabilize the target vessel. The heart rate was controlled with a diltiazem drip.
      Cardiopulmonary bypass was not necessary in any case. The right coronary artery
      was bypassed in three patients, the posterior descending artery branch in ten
      patients, and the terminal circumflex of the left coronary artery in one. After
      grafting, patency of the anastomosis was demonstrated by Doppler echocardiogram.
      Two patients had left anterior descending artery (LAD) grafts with LIMA (left
      mammary artery) and RGEA grafts performed simultaneously with two port access
      incisions. No patient had perioperative mortality or complications. No patient
      had recurrent angina. Doppler color echocardiographic imaging studies before
      discharge confirmed patency of the graft in 13 of 14 cases. In one case, the
      gastroepiploic artery could not be visualized. Angiographic visualization was
      positive in seven cases; seven patients were not studied yet. The gastroepiploic
      artery is an excellent conduit for vascularization of the inferior aspect of the
      heart. The operation can be done with a minimally invasive technique and without
      the use of cardiopulmonary bypass. This approach seems especially applicable in
      selective reoperative cases.

PMID- 9591174
TI  - Effects of hypothermia on blood endogenous endotoxin levels during
      cardiopulmonary bypass.
AB  - Endotoxin activates white blood cells and complement and produces a spectrum of
      clinical syndromes ranging from fever to septic shock. Although production of
      endogenous endotoxemia during cardiopulmonary bypass (CPB) has recently been
      reported, the role of hypothermia on endotoxemia is not clear. In this study, we
      evaluated the effects of moderate (24-28 degrees C) and mild (32-34 degrees C)
      hypothermia on blood endotoxin levels. The study population consisted of 20
      patients who underwent coronary artery bypass grafting (CABG) with CPB. Moderate
      systemic hypothermia was applied during aortic cross-clamping in ten patients
      (group 1) and mild hypothermia in the remaining ten patients (group 2). The mean
      rectal temperatures were 26.8 +/- 1.2 degrees C in group 1 and 33.8 +/- 0.8
      degrees C in group 2. The blood samples for endotoxin level measurements were
      obtained before CPB, during aortic cross-clamping, immediately after the release
      of the cross-clamp, 20 minutes after the release of the cross-clamp, after CPB,
      and 2 hours postoperatively. There were no endotoxins in any of the samples
      before CPB, but it was detected after CPB in both groups. The endotoxin levels
      were significantly higher in group 1 than in group 2. The present study suggests
      that when hypothermia is the technique of choice, the deleterious effects of
      endotoxemia on patients with comorbidity must be considered.

PMID- 9591175
TI  - Chronic estrogen replacement inhibits aortic intimal hyperplasia independent of
      serum lipids.
AB  - The role of estrogens in providing atheroprotection has been well documented in
      both epidemiologic and experimental studies. This phenomenon has traditionally
      been attributed to the beneficial lipid-modifying effects of estrogens. Yet lipid
      alterations may not be the sole mechanism of estrogen-mediated cardiovascular
      protection. Previous studies have utilized models of either diet- or injury
      induced atherosclerosis. As such, the interrelationship between estrogens,
      lipids, and atherosclerosis remains unclear. The purpose of this study was to
      determine the effect of ovariectomy with or without estrogen replacement on the
      development of aortic intimal hyperplasia. Although we acknowledge the influence
      of estrogens on the lipid profile, we hypothesized that estrogens are
      atheroprotective independent of changes in serum lipids. Twelve Warhill ewes (7
      11 years old) were randomized to sham (2 sheep) operation, ovariectomy (OVx-5
      sheep), or ovariectomy with 17 beta-estradiol replacement (OVxE-5 sheep). Serum
      cholesterol and triglyceride levels were measured at 0, 6, and 12 months.
      Necropsy was performed at 6 and 12 months with histologic morphometric analysis
      of the aortoiliac bifurcation. Ovariectomy resulted in intimal thickening in
      comparison to the sham (p < 0.0001) and hormone replacement group (p < 0.0001).
      Serum cholesterol and triglyceride levels were similar and normal (40-60 mg/dl)
      among all groups. Estradiol abrogates aortic intimal hyperplasia following
      ovariectomy independent of the hormone's effects on lipid metabolism.

PMID- 9591177
TI  - On "Surgical treatment of diastolic dysfunction".

PMID- 9591176
TI  - Diastolic hibernation masquerading as constrictive pericarditis.
AB  - BACKGROUND: Hibernating myocardium has traditionally been characterized in terms
      of systolic dysfunction. METHODS: We describe a case in which a 75-year-old
      patient with significant coronary artery disease was operated upon for classic
      constrictive pericarditis. RESULTS: At sternotomy, there was no evidence of
      pericarditis, but marked diastolic without systolic dysfunction remained. After
      successful coronary revascularization, the patient immediately exhibited dramatic
      improvement of diastolic performance. Ex vivo evaluation of myocardial
      contractile function revealed normal myocardial adrenergic responsiveness,
      indicating a reversible impairment of contractility. CONCLUSION: Diastolic
      hibernation may therefore represent a unique form of surgically correctable
      restrictive cardiomyopathy.

PMID- 9591178
TI  - Ultrasonic debridement of mitral calcification.
AB  - Dense annular calcification to the valve attachment is particularly hazardous
      during mitral valve replacement because of the difficulty of placing sutures and
      the risk of atrioventricular rupture. We report 11 patients who underwent
      decalcification of the mitral anulus with the Cavitron Ultrasound Surgical
      Aspirator (CUSA) during mitral valve replacement. This resulted in a greatly
      simplified suture placement and prosthetic valve seating as well as enlargement
      of the annular orifice. Four other patients underwent CUSA debridement of the
      anterior leaflet of the mitral valve during concomitant aortic valve replacement
      and CUSA debridement of the aortic anulus. There were no operative deaths or
      major complications. Ultrasonic debridement is a useful adjunct in the surgical
      management of the heavily calcified mitral valve.

PMID- 9591179
TI  - Successful management of a postinfarction left ventricular rupture using a
      sutureless technique with concomitant myocardial revascularization.
AB  - We present a case of left ventricular (LV) rupture that occurred on the second
      day after inferolateral myocardial infarction (MI). An aggressive diagnostic
      approach with rapid coronary angiography prior to surgical repair provides a
      benefit characterized postoperatively by complete recovery of myocardial
      contractility in the akinetic infarcted area. We believe that coronary artery
      disease associated with subacute ventricular rupture may, in fact, be better
      investigated and simultaneously treated under a protocol of early surgical
      repair.

PMID- 9591180
TI  - Repair of left ventricular aneurysm by autologous pericardial patch reinforcement
      (capping)--follow-up results.

PMID- 9591181
TI  - Diameters of the pulmonary arteries and veins as an indicator of bilateral and
      unilateral pulmonary blood flow in patients with congenital heart disease.
AB  - OBJECTIVES: This study was done to clarify which diameter, that of the pulmonary
      arteries (PAs) or that of the pulmonary veins (PVs), more precisely reflects
      pulmonary blood flow (PBF) bilaterally and unilaterally. METHODS: To evaluate
      bilateral PBF, we studied 15 consecutive patients with Kawasaki disease as normal
      patients and 30 patients with tetralogy of Fallot who received cardiac
      catheterization. To evaluate unilateral PBF, 20 patients with various congenital
      heart diseases undergoing cineangiography and lung perfusion scintigraphy were
      studied. The diameter of PA was measured immediately proximal to the origin of
      the first lobar branches bilaterally, and right PA area, left PA area, PA area
      (mm2), and PA index (mm2/m2) were calculated. The diameter of PV was also
      measured distal to the junction with the left atrium. Right PV area, left PV
      area, PV area (mm2), and PV index (mm2/m2) were calculated from these diameters.
      Pulmonary blood flow (PBF) was obtained by the Fick method during
      catheterization. To evaluate unilateral PBF, PBF was divided into right and left
      PBF according to the right/left perfusion ratio measured by lung perfusion
      scintigraphy. RESULTS: Evaluation of bilateral PBF was as follows: in normal
      patients, PA and PV areas were correlated with body surface area (r = 0.88, p =
      0.0001 and r = 0.93, p = 0.0001); PA index and PV index ranged from 248 to 436
      (mean = 343) mm2/m2 and from 346 to 595 (mean = 466) mm2/m2, respectively, and
      were constant irrespective of body surface area; PA and PV areas were correlated
      with PBF in normal patients, as well as in patients with tetralogy of Fallot.
      There was a better correlation between PV area and PBF than between PA area and
      PBF in normal patients, as well as a significantly better correlation in patients
      with tetralogy of Fallot. Evaluation of unilateral PBF was as follows: right PV
      area was correlated with right PBF (p = 0.0002), while right PA area was not;
      left PV area and left PA area were correlated with left PBF; right/left PV area
      ratio was correlated with the right/left perfusion ratio with better agreement
      than right/left PA area ratio. CONCLUSION: Our data suggest that the size of PVs
      in patients with congenital heart disease may be more useful than the size of PAs
      to indicate bilateral and unilateral PBF than the size of PAs. Differences in PV
      area of each lung may be a suitable indicator of discrepancy in blood flow to
      each lung.

PMID- 9591182
TI  - Extended and total simultaneous aortic replacement: latest technical
      modifications and improved results with thirty-four patients.
AB  - Aortic disease frequently requires extended and multiple resections.
      Occasionally, resection of the entire aorta may be indicated. At our Institution,
      from 1982 to 1994, 34 patients were operated upon for extended and total
      simultaneous aortic replacement. In seven patients, the aorta was replaced from
      valve to bifurcation; in 27, the aortic valve was included. Operations were
      performed with circulatory arrest under profound hypothermia. As the first step,
      the aortic valve and ascending aorta are replaced and the coronary arteries are
      reconnected, following which the aortic arch is reconstructed. Meanwhile, a
      second surgical team proceeds to open the thoracoabdominal aorta and tie up the
      intercostal orifices. If circulatory arrest is likely to exceed 60 minutes, the
      aortic graft is clamped and upper body perfusion (1000 cc/min) is begun. Finally,
      the thoracoabdominal aorta is fully replaced. Cardiopulmonary bypass (CPB) with
      rewarming is resumed only after the operation has been completed. Thirty-four
      patients survived operation; five died within 1 month for an overall mortality of
      14.7%. No mortality occurred in the most recent nine operations. No permanent
      spinal neurological deficits occurred. Total simultaneous aortic replacement for
      treatment of extended aortic disease may be reasonable using our approach.

PMID- 9591183
TI  - Anomalous origin of the left coronary artery from the pulmonary artery in an
      adult: tubular reconstruction of the left main coronary artery under coronary
      perfusion.
AB  - A 38-year-old female with anomalous origin of the left coronary artery (LCA) from
      pulmonary artery was surgically corrected by tubular reconstruction of the left
      main coronary artery (LMCA) using the pulmonary artery wall, and this repair was
      performed under beating heart. Thus, the pulmonary artery was divided above the
      orifice level and just above the pulmonary valve, and the commissure between
      nonfacing and left side sinuses was dissected away from the pulmonary artery wall
      to obtain lateral flaps. The pulmonary artery defect was reconstructed with a
      roll using an autologous pericardial patch, while the detached commissure was
      suspended on the pericardial patch. The long tube constructed using pulmonary
      artery tissue was anastomosed to the anterior aspect of the ascending aorta.
      These procedures were performed under beating heart simply by clamping the LMCA,
      since the preoperative myocardial contrast echocardiography confirmed the
      adequate coronary collateral flow from the right circulation. The postoperative
      course was uneventful, and a coronary artery angiogram demonstrated a widely
      patent LMCA. Our experience suggests that, in adult cases, this procedure could
      be performed without myocardial ischemia simply by clamping the LMCA because of
      well-developed coronary collateral arteries. The safety of this technique could
      be confirmed by myocardial contrast echocardiography.

PMID- 9591184
TI  - Pericostal sutures to reinforce sternal closure after cardiac surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: An increasing number of elderly and medically
      complex patients are undergoing cardiac surgery and are at increased risk for
      sternal dehiscence. A technique of sternal closure reinforcement with pericostal
      wires is described, and results are reviewed. METHODS: After placement of the
      standard peristernal wires, one or two sets of pericostal wires were placed
      around ribs in the mid-portion of the sternotomy to reinforce the closure. A
      retrospective study over a 6-year period was carried out to determine the
      incidence of sternal dehiscence and any associated complications. Pericostal
      wires were used in well over 50% of cases. RESULTS: The incidence of sternal
      dehiscence was 4 out of 1048 operations (0.38%). No adverse effects of the
      pericostal wires were identified. CONCLUSIONS: Frequent use of pericostal wires
      is associated with a low incidence of sternal dehiscence.

PMID- 9591185
TI  - Failure of unipolar pacemaker secondary to subcutaneous emphysema.
AB  - Failure of a pacemaker to capture may be related to several factors. This report
      describes a case with loss of capture of a unipolar pacemaker following the
      development of subcutaneous emphysema. Once the diagnosis is established,
      treatment options include tube thoracostomy, pressure dressing, aspiration of air
      or fluid from the pocket, or insertion at a new site.

PMID- 9591186
TI  - Protocol design considerations that relate to demonstrating the safety and
      effectiveness of chemopreventive agents.
AB  - As with other drugs, applications for marketing approval of new chemopreventive
      agents in the United States must include data from adequate and well-controlled
      clinical trials that demonstrate effectiveness and safety for the intended use.
      Knowledge of a drug's pharmacologic actions and metabolism may benefit protocol
      design, by identifying the patient populations and dosing schedules associated
      with a favorable risk/benefit profile. With availability of appropriate
      preclinical data, including standard assessments of an agent's toxicology,
      effects on reproductive performance, and genotoxicity, initial Phase I studies of
      1-3 months may be performed in normal volunteers or an appropriate higher risk
      population. For chronic dosing studies of longer duration, preclinical toxicology
      studies of longer duration are relevant. Enrollment in chemoprevention studies
      should be directed toward individuals at sufficient risk of developing cancer so
      that potential benefit may counterbalance the unpredictable and possibly serious
      adverse effects that may be observed with prolonged administration of a study
      drug. Phase I and II studies with clinical dosing lasting up to 12 months often
      afford opportunities to assess drug effect on surrogate endpoint biomarkers that
      may correlate with endpoints of clinical effectiveness. Phase III and late phase
      II chemopreventive investigations should routinely utilize a prospective,
      randomized study design (double-masked and placebo-controlled, when possible). To
      support marketing approval, there must be evidence that a chemopreventive agent
      significantly delays or prevents the occurrence of malignancy, with acceptable
      safety. In some circumstances, modulation of a surrogate marker may provide a
      basis for marketing approval, before more definitive endpoint data become
      available. However, the acceptability of a surrogate depends on the nature and
      quality of the data supporting its predictive value. Given the considerations of
      large study size, long duration, and high cost that may hamper development of
      potential agents, studies designed to examine the predictive value of surrogate
      endpoint biomarkers are of great importance to the future development of
      chemoprevention research.

PMID- 9591187
TI  - Research and development of cancer chemopreventive agents in China.
AB  - Since the late 1970s, a comprehensive search for cancer chemopreventive agents
      has been established in our Institute. A series of new retinoids have been
      synthesized and screened on the basis of established methodologies of
      experimental chemoprevention in vitro as well as in vivo. Pharmacological studies
      demonstrated that N-4-(carboxyphenyl)retinamide (RII) induces cell
      differentiation of HL-60 cells and inhibits dimethylnitrosamine-induced
      carcinogenesis of the forestomach in mice, 7,12-dimethylbenz[a]anthracene (DMBA)
      induced papilloma in mouse skin, and DMBA-induced carcinogenesis of the buccal
      pouch in Syrian golden hamsters. It significantly promoted lymphoblastic
      transformation and activated macrophages. In further studies, RII significantly
      inhibited ornithine decarboxylase activity. After 6 months of chronic
      toxicological studies in rats and dogs, RII was recommended for clinical trial.
      Phase II studies found that RII is effective in treating oral and vulvar
      leukoplakia. It is also effective in treating myelodysplastic syndrome and
      dysplasia of uterine cervix. The chalcone retinoidal compounds were discovered
      when the search for new retinoids with less toxicity and higher potency led to
      third-generation retinoids, which were synthesized and screened. Structure
      activity relationship studies found that 3,5-di-tert-butyl-4-methoxy-4-carboxyl
      chalcone (R9158) is the most active inhibitor of a variety of cancer cells. It
      has no effect on the Colony Forming Unit-Granulocyte/Macrophage (CFU-GM) of bone
      marrow in mice. In in vivo studies, R9158 showed a remarkable inhibition of
      chondrosarcoma in rats. It had no cross-resistance to vincristine, but was cross
      resistant to all-trans retinoic acid. Red ginseng, a processed Panax ginseng, is
      considered a typical tonic in traditional Chinese medicine. Our studies
      demonstrated that red ginseng extract inhibited DMBA-induced skin papilloma
      significantly. Experiments showed that glycyrrhetinic acid inhibited croton oil
      induced ear edema in mice. It also inhibited epidermal ornithine decarboxylase as
      well as the rapid DNA damage induced by the carcinogen benzo[a]pyrene (B[a]P).
      Our pharmacological studies demonstrated that Chinese gallotannin inhibited the
      malignant transformation of B[a]P-induced V79 cells in vitro and B[a]P-induced
      pulmonary adenoma in A/J mice in vivo significantly.

PMID- 9591188
TI  - Advances in the development of farnesyltransferase inhibitors: substrate
      recognition by protein farnesyltransferase.
AB  - A variety of compounds that show promise in cancer chemotherapy and
      chemoprevention have been identified as farnesyltransferase inhibitors. These can
      be classified into mainly two different types of inhibitors, farnesyl diphosphate
      competitors and CAAX peptidomimetics. The former type acts by competitively
      inhibiting farnesyltransferase with respect to one of the substrates, farnesyl
      diphosphate, whereas the latter type acts by mimicking the other substrate, the C
      terminal CAAX motif of Ras protein. One example of a farnesyl diphosphate
      competitor is manumycin, an antibiotic detected in the culture media of a
      Streptomyces strain. The CAAX peptidomimetics were developed based on the unique
      property of farnesyltransferase to recognize the CAAX motif at the C-terminus of
      the protein substrate. Our recent studies have focused on understanding the
      structural basis of this CAAX recognition. By using in vitro mutagenesis,
      residues of yeast farnesyltransferase important for the recognition of the CAAX
      motif have been identified. Two of these residues are closely located at the C
      terminal region of the beta-subunit of farnesyltransferase. These and other
      results on the structural basis of the CAAX recognition may provide information
      valuable for structure-based design of farnesyltransferase inhibitors.

PMID- 9591189
TI  - Chemopreventive effect of perillyl alcohol on 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone induced tumorigenesis in (C3H/HeJ X A/J)F1 mouse lung.
AB  - This study was designed to test the chemopreventive potential of perillyl
      alcohol, an inhibitor of farnesyltransferase, in a mouse lung tumor bioassay.
      Perillyl alcohol is a naturally occurring monoterpene found in lavender,
      cherries, and mint. We have shown previously that the majority of lung tumors in
      this bioassay have an activating mutation in the K-ras gene, which occurs early
      in the development of mouse lung carcinogenesis. The Ras protein undergoes a
      series of post-translational modifications, the first of which is farnesylation
      at the cysteine of the C-terminal CAAX motif. These modifications lead to the
      anchoring of Ras p21 to the plasma membrane in its biologically active state.
      Activated Ras p21 couples growth regulatory signals from receptor tyrosine
      kinases to cytoplasmic second messengers. In a preliminary study, we determined
      the maximum tolerated dose of perillyl alcohol to be 75 mg/kg body weight. For
      the bioassay, 5-week-old male (C3H/HeJ X A/J) F1 hybrid mice were randomized into
      trial groups, and treated with perillyl alcohol three times per week i.p.,
      starting 1 week prior to initiation with the carcinogen NNK, and continuing for
      22 weeks after initiation. Our results show a 22% reduction in tumor incidence,
      and a 58% reduction in tumor multiplicity. Our study demonstrates that perillyl
      alcohol is an effective chemopreventive compound in the mouse lung tumor
      bioassay.

PMID- 9591190
TI  - Inhibitory effects of curcumin on tumorigenesis in mice.
AB  - Curcumin (diferuloylmethane), the naturally occurring yellow pigment in turmeric
      and curry, is isolated from the rhizomes of the plant Curcuma longa Linn.
      Curcumin inhibits tumorigenesis during both initiation and promotion (post
      initiation) periods in several experimental animal models. Topical application of
      curcumin inhibits benzo[a]pyrene (B[a]P)-mediated formation of DNA-B[a]P adducts
      in the epidermis. It also reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced increases in skin inflammation, epidermal DNA synthesis, ornithine
      decarboxylase (ODC) mRNA level, ODC activity, hyperplasia, formation of c-Fos,
      and c-Jun proteins, hydrogen peroxide, and the oxidized DNA base 5-hydroxymethyl
      2'-deoxyuridine (HmdU). Topical application of curcumin inhibits TPA-induced
      increases in the percent of epidermal cells in synthetic (S) phase of the cell
      cycle. Curcumin is a strong inhibitor of arachidonic acid-induced edema of mouse
      ears in vivo and epidermal cyclooxygenase and lipoxygenase activities in vitro.
      Commercial curcumin isolated from the rhizome of the plant Curcuma longa Linn
      contains 3 major curcuminoids (approximately 77% curcumin, 17% demethoxycurcumin,
      and 3% bisdemethoxycurcumin). Commercial curcumin, pure curcumin, and
      demethoxycurcumin are about equipotent as inhibitors of TPA-induced tumor
      promotion in mouse skin, whereas bisdemethoxycurcumin is somewhat less active.
      Topical application of curcumin inhibits tumor initiation by B[a]P and tumor
      promotion by TPA in mouse skin. Dietary curcumin (commercial grade) inhibits
      B[a]P-induced forestomach carcinogenesis, N-ethyl-N'-nitro-N-nitrosoguanidine
      (ENNG)-induced duodenal carcinogenesis, and azoxymethane (AOM)-induced colon
      carcinogenesis. Dietary curcumin had little or no effect on 4-(methylnitosamino)
      1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis and 7,12
      dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in mice. Poor
      circulating bioavailability of curcumin may account for the lack of lung and
      breast carcinogenesis inhibition.

PMID- 9591191
TI  - Chemoprevention by naturally occurring and synthetic agents in oral, liver, and
      large bowel carcinogenesis.
AB  - A number of naturally occurring compounds and several related synthetic agents
      were confirmed to exert chemopreventive properties against carcinogenesis in the
      digestive organs. Phenolic compounds, widely distributed as plant constituents,
      possess chemopreventive activities in tongue, liver, and large bowel of rodents.
      Of them, a simple phenolic protocatechuic acid seems to be a promising compound.
      Organosulfur compounds contained in the cruciferous vegetables and known to
      activate detoxifying enzymes are regarded as a candidate group for cancer
      preventive agents. We proved a strong protective effect of S
      methylmethanethiosulfonate, a constituent in these vegetables, on azoxymethane
      (AOM)-induced large bowel carcinogenesis. Some oxygenated carotenoids
      (xanthophylls) are reported to have antitumor effects. Naturally occurring
      xanthophylls astaxanthin and canthaxanthin have considerable preventive
      activities on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinogenesis and
      AOM-induced large bowel carcinogenesis. A novel synthesized retinoidal
      butenolide, KYN-54, which suppresses large bowel as well as tongue carcinogenesis
      could be a useful agent for prevention of digestive organ cancers. Some trace
      elements are known to have anticarcinogenic effects. Magnesium hydroxide, a
      protective agent in colorectal carcinogenesis, inhibits c-myc expression and
      ornithine decarboxylase activity in the mucosal epithelium of the intestine. Our
      results show that many agents with preventive effects in tongue, liver, and large
      bowel control carcinogen-induced hyperproliferation of cells in these organs.
      Carcinogens used to induce large bowel cancers also induce apoptosis in the
      target sites. Telomerase activity is increased in the tissues of preneoplastic as
      well as neoplastic lesions in experimental models such as
      dimethylbenz[a]anthracene-induced oral carcinogenesis in hamsters. These could be
      useful biomarkers in studies for cancer chemoprevention.

PMID- 9591192
TI  - Chemopreventive properties of indole-3-carbinol (I3C): inhibition of DNA adduct
      formation of the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo [4,5
      b]pyridine (PhIP), in female F344 rats.
AB  - Indole-3-carbinol (I3C), a naturally occurring inhibitor of experimental
      carcinogenesis, was evaluated for its possible inhibitor effect on DNA-adduct
      formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a dietary
      mutagen, in female F344 rats. PhIP is a mammary carcinogen in female F344 rats
      and a colon carcinogen in male F344 rats. Four-week-old animals (4/group) were
      maintained on powdered AIN-76A diet with or without 13C (0.02% or 0.1%, w/w) for
      58 days. PhIP (0.04%, w/w) was added to the diet from days 15 through 42. Animals
      were killed on days 43 and 58. DNA isolated from mammary epithelial cells (MECs),
      colon, liver, and white blood cells (WBCs) was analyzed for PhIP-DNA adducts by
      32P-postlabeling assays. On day 43, adduct levels of the group receiving 0.1%
      dietary I3C decreased in MECs (91.9%), colon (67.2%), liver (69.2%), and WBCs
      (82.3%). On day 58, DNA adduct formation was inhibited in the colon (81.3-82.2%)
      at both dietary I3C concentrations, and in liver (46.8%) only in the animals fed
      0.1% I3C. When incorporated in the diet after exposure to dietary PhIP (0.04% for
      2 weeks), 13C (0.1%) had no effect on the rate of removal of PhIP-DNA adducts
      over the next 28 days. It is concluded that dietary I3C inhibits PhIP-DNA adduct
      formation in the female F344 rat but does not affect adduct removal. I3C may be a
      promising chemopreventive agent in PhIP-induced carcinogenesis in rats.

PMID- 9591193
TI  - Influence of tea catechins on the digestive tract.
AB  - Tea catechins undergo various metabolic changes after they are taken orally,
      though a large percentage are excreted intact with the feces. Epidemiological
      studies suggest a protective effect of tea against various human cancers,
      including colon and rectum. The bactericidal property of tea catechins plays
      several roles in the digestive tract. In the small intestine, catechins inhibit
      alpha-amylase activity, and a certain amount is absorbed into the portal vein.
      Although catechins are bactericidal, they do not affect lactic acid bacteria.
      Including tea catechins in the diet for several weeks decreases putrefactive
      products and increases organic acids by lowering pH. These changes were achieved
      in tube-fed patients by administering 100 mg of tea catechins (equivalent to a
      cup of green tea) three times daily with meals for 3 weeks. When catechin
      administration ceased, the effects reversed after 1 week. Catechins should be
      considered further in colon carcinogenesis studies.

PMID- 9591194
TI  - Tea antioxidants in cancer chemoprevention.
AB  - In recent years, the concept of cancer chemoprevention has matured greatly.
      Significant reversal or suppression of premalignancy in several sites by
      chemopreventive agents appears achievable. This article summarizes experimental
      data on chemopreventive effects of tea polyphenols in different tumor bioassay
      systems. Tea (Camellia sinensis) is cultivated in about 30 countries, and is the
      most widely consumed beverage in the world. Three main commercial tea varieties-
      green, black, and oolong--are usually consumed, but most experimental studies
      demonstrating the antimutagenic and anticarcinogenic effects of tea have been
      conducted with water extract of green tea, or a polyphenolic fraction isolated
      from green tea (GTP). The majority of these studies have been conducted in a
      mouse skin tumor model system where tea is fed either as water extract through
      drinking water, or as purified GTP. GTP has been shown to exhibit antimutagenic
      activity in vitro, and inhibit carcinogen- as well as UV-induced skin
      carcinogenesis in vivo. Tea consumption has also been shown to afford protection
      against chemical carcinogen-induced stomach, lung, esophagus, duodenum, pancreas,
      liver, breast, and colon carcinogenesis in specific bioassay models. Several
      epicatechin derivatives (polyphenols) present in green tea have been shown to
      possess anticarcinogenic activity; the most active is (-)-epigallocatechin-3
      gallate, which is also the major constituent of GTP. The mechanisms of tea's
      broad cancer chemopreventive effects are not completely understood. Several
      theories have been put forward, including inhibition of UV- and tumor promoter
      induced ornithine decarboxylase, cyclo-oxygenase, and lipoxygenase activities,
      antioxidant and free radical scavenging activity; enhancement of antioxidant
      (glutathione peroxidase, catalase, and quinone reductase) and phase II
      (glutathione-S-transferase) enzyme activities; inhibition of lipid peroxidation,
      and anti-inflammatory activity. These properties of tea polyphenols make them
      effective chemopreventive agents against the initiation, promotion, and
      progression stages of multistage carcinogenesis.

PMID- 9591195
TI  - Chemopreventive effect of green tea (Camellia sinensis) against cigarette smoke
      induced mutations (SCE) in humans.
AB  - Green tea (Camellia sinensis) is consumed daily between the meals or after meals
      in Japan and other Asian countries. In recent years, green tea and its major
      polyphenolics have been demonstrated to prevent chemically induced tumors in a
      variety of experimental animal models system. The exact mechanism(s) of its
      anticarcinogenic activity remains to be elucidated, but green tea polyphenolics
      have demonstrated antimutagenic, anticarcinogenic, antioxidant, and
      antipromotional effects, including inhibition of Phase I and inducing Phase II
      enzymes. Enzyme activities of glutathione peroxidase, catalase, and quinone
      reductase, and glutathione S-transferase are also induced. However, a paucity of
      green tea effects in humans prompted us to investigate antimutagenic effects of
      green tea against smoke-induced mutation in humans. Chemopreventive effects of
      green tea and coffee among cigarette smokers were examined in 52 clinically
      healthy male subjects between 20-51 years of age. Blood specimens were obtained
      from non-smokers (Group I), smokers (II), smokers consuming green tea (III), and
      smoker/coffee drinkers (IV). The mean years of cigarette smoking (> 10
      cigarettes/day) of Groups II, III, and IV ranged from 13.4-14.7 years. Daily
      intake of green tea and coffee was 3 cups/day/6 months (III and IV). The
      frequencies of sister-chromatid exchange (SCE) in mitogen-stimulated peripheral
      lymphocytes from each experimental group were determined and statistically
      analyzed. SCE rates were significantly elevated in smokers (9.46 +/- 0.46) vs.
      non-smokers (7.03 +/- 0.33); however, the frequency of SCE in smokers who
      consumed green tea (7.94 +/- 0.31) was comparable to that of non-smokers,
      implying that green tea can block the cigarette-induced increase in SCE
      frequency. Coffee, by contrast, did not exhibit a significant inhibitory effect
      on smoking-induced SCE.

PMID- 9591197
TI  - Cancer prevention by natural carotenoids.
AB  - Epidemiological investigations have shown that cancer risk is inversely related
      to the consumption of green and yellow vegetables and fruits. Since beta-carotene
      is present in abundance in these vegetables and fruits, it has been investigated
      extensively as a possible cancer preventive agent. However, various carotenoids
      that coexist with beta-carotene in vegetables and fruits also have
      anticarcinogenic activity. Some of them, such as alpha-carotene, showed higher
      potency than beta-carotene in suppressing experimental carcinogenesis. Thus, we
      have carried out more extensive studies on cancer-preventive activities of
      natural carotenoids, which found that lycopene and lutein had potent
      anticarcinogenic activity. In the present study, the cancer-preventive activity
      of phytoene was also confirmed biotechnologically when mammalian cells producing
      phytoene were resistant to H-ras-induced cell transformation. Further studies on
      various natural carotenoids besides beta-carotene should be continued to obtain
      more information about the potential of natural carotenoids in the field of
      cancer prevention.

PMID- 9591196
TI  - Chemopreventive potential of thiol conjugates of isothiocyanates for lung cancer
      and a urinary biomarker of dietary isothiocyanates.
AB  - Natural and synthetic isothiocyanates (ITCs) are versatile chemopreventive agents
      in many animal systems. We have shown that phenethyl ITC (PEITC) and 6
      phenylhexyl ITC (PHITC) are potent inhibitors against lung tumorigenesis induced
      by tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in
      both mouse and rat. The mechanism by which these ITCs inhibited lung
      tumorigenesis is attributed to their ability to decrease cytochrome P450 (P450)
      enzyme activities involved in the activation of NNK. Recently, we have found that
      thiol conjugates of ITCs inhibit P450 enzymes and are effective inhibitors of
      lung tumorigenesis. This is significant because conjugation with cellular thiols
      is the major route of ITC metabolism via the mercapturic acid pathway in rodents
      and humans. The thiol conjugates are less pungent and potentially less toxic, and
      they are more soluble and chemically less reactive than ITCs. These properties
      raise the prospect of substituting thiol conjugates for ITCs as chemopreventive
      agents. Furthermore, although ample rodent studies have established that ITCs
      inhibit tumorigenesis, the protective role of dietary ITCs against human cancers
      has not yet been established. As a prerequisite for such human studies, we have
      developed an HPLC-based assay, based on the condensation reaction of ITCs or
      conjugates with 1,2-benzenedithiol, for measuring a cyclocondensation product in
      human urine as an uptake biomarker of total ITCs. This assay was validated using
      urine samples from subjects who had ingested a known amount of watercress or
      mustard in a controlled diet. The assay is convenient and rapid, showing promise
      for analyzing urine samples obtained from population-based studies. Results from
      two such studies are presented to illustrate the potential application of this
      biomarker in epidemiologic studies.

PMID- 9591198
TI  - Effect of early vs. late administration of 4-hydroxyphenylretinamide (4-HPR) on N
      methyl-N-nitrosourea (MNU)-induced mammary tumorigenesis.
AB  - Mammary tumors were induced in 48-52-day-old female Sprague-Dawley rats in
      metestrus or diestrus with a single jugular injection of MNU (50 mg/kg). Control
      rats received the saline vehicle (Group 4 n = 9). Rats were fed 4% Teklad diet
      containing either 0 (Group 3, n = 20) or 782 mg 4-HPR/kg diet. 4-HPR
      supplementation was initiated either 1 week prior to (Group 1, n = 14) or 4 weeks
      following MNU administration (Group 2, n = 19). Neither body weight nor food
      intake differed significantly between treatment groups. Feeding of 4-HPR 1 week
      prior to tumor induction reduced the number of tumors (0.8 +/- .2) when compared
      to MNU control rats (2.1 +/- .4). Immunohistochemical staining of mammary tumor
      sections for PCNA was quantitated by microdensitometry and expressed as an
      HSCORE. No differences in HSCORE were observed between tumor groups although the
      percentage of nuclear area occupied by intermediate and darkly stained nuclei was
      reduced in the late 4-HPR group. GC-->AT transitions in codon 12 of the H-ras
      gene were detected in 50% (12/24) of MNU control tumors, 60% (6/10) of early 4
      HPR tumors, and 38% (6/16) of late 4-HPR tumors. Mutation rates did not differ
      significantly between groups. 4-HPR appears to be a more effective
      chemopreventive when fed during the initiation period.

PMID- 9591199
TI  - Cancer prevention by organosulfur compounds from garlic and onion.
AB  - Environmental compounds are known to be involved in both the generation and
      prevention of many human cancers. It is important to discover naturally occurring
      or synthetic compounds which can block the process of carcinogenesis. We have
      focused attention on several organosulfur compounds (OSCs) in garlic and onion,
      and analyzed their potential for chemoprevention in the post-initiation stage in
      a liver medium-term bioassay (Ito test) and a multi-organ carcinogenesis
      bioassay. In the ITO test, rats were given diethylnitrosamine (DEN), 200 mg/kg
      b.w., i.p.; starting 2 weeks later they were treated with test chemicals for 6
      weeks and then killed. All rats were subjected to 2/3 hepatectomy 1 week after
      the start of test chemical treatment. Inhibitory effects of a number of compounds
      could be identified in terms of reduced numbers and areas of liver glutathione S
      transferase placental (GST-P) positive foci. In the multi-organ carcinogenesis
      bioassay, rats were given DEN, N-methyl-N-nitrosourea, N-butyl-N-(4
      hydroxybutyl)nitrosamine, N,N'-dimethylhydrazine, and dihydroxy
      dipropylnitrosamine during the first 4 weeks, followed by test chemicals for 24
      weeks. Various organs were examined. As a result, oil-soluble OSCs such as methyl
      propyl disulfide and propylene sulfide demonstrated inhibitory effects on the
      development of GST-P positive foci. Moreover, water-soluble OSCs such as S
      methylcysteine and cysteine similarly decreased GST-P focus formation. In
      contrast, OSCs such as diallyl sulfide, diallyl trisulfide, and allyl methyl
      trisulfide enhanced formation of such altered hepatocellular foci. Inhibitory
      potential for colon and renal carcinogenesis was observed in rats treated with
      diallyl disulfide. Thus, the results indicate that some OSCs exert
      chemopreventive effects on chemical carcinogenesis. It must, however, be borne in
      mind that they may also demonstrate promotion potential, depending on the organ
      examined.

PMID- 9591200
TI  - Initial study on naturally occurring products from traditional Chinese herbs and
      vegetables for chemoprevention.
AB  - A number of naturally occurring products from vegetables and herbs exert
      chemopreventive properties against carcinogenesis. In this paper, two such
      compounds, isolated from garlic and from a traditional Chinese medicinal herb,
      are described for review. Elemene, isolated from the Chinese medicinal herb
      Rhizoma zedoariae, was shown to exhibit antitumor activity in human and murine
      tumor cells in vitro and in vivo. This novel antineoplastic agent has substantial
      clinical activity against various tumors. The in vitro effect of elemene on the
      growth of leukemia cells was evaluated by MTT assay. The IC50 values of elemene
      for promyelocytic leukemia HL-60 cells and erythroleukemia K562 cells were 27.5
      micrograms/mL and 81 micrograms/mL, respectively, while IC50 for peripheral blood
      leukocytes (PBL) was 254.3 micrograms/mL. The inhibitory effect of elemene on
      proliferation of HL-60 cells was associated with cell cycle arrest from S to G2M
      phase transition and with induction of apoptosis. The apoptosis of tumor cells
      was confirmed by DNA ladder formation on gel electrophoresis and characteristic
      ultrastructural alterations. The results also demonstrated that inhibitory
      effects of allicin, a natural organosulfide from garlic, on proliferation of
      tumor cells were associated with the cell cycle blockage of S/G2M boundary phase
      and induction of apoptosis. These findings suggest that induction of apoptosis
      may contribute to the mechanisms of antitumor activity of elemene and allicin,
      which merit investigation as potential chemoprevention agents in humans.

PMID- 9591201
TI  - Can we improve breast pathology reporting practices? A community-based breast
      pathology quality improvement program in New Hampshire.
AB  - We implemented a regional quality assurance program in New Hampshire (NH) to
      evaluate breast pathology practices and attempt to improve the completeness of
      information provided in breast surgical pathology reports. We also assessed the
      degree to which NH pathologists agree with National Guidelines. The program's
      objective was to promote a consistent standard of care for patients whose breast
      pathology is interpreted in NH. Using a sequential survey technique, we were able
      to obtain consensus on breast tissue report content that was similar to National
      Guidelines. We also found that 52% of the reporting elements improved in the post
      intervention period, although only one reached statistical significance. In
      conclusion, pathology interpretation is the "gold standard" for determining both
      screening effectiveness and subsequent treatment of breast cancer, yet
      variability in breast tissue reporting exists. It is critical that more research
      be done to improve breast pathology interpretation and reporting practices.

PMID- 9591202
TI  - Physical activity patterns of urban African Americans.
AB  - This study assessed physical activity patterns in a sample of urban African
      Americans, whose participation in physical activity has not previously been well
      described. From questions administered by interviewers during health fair
      screenings in 19 churches in East Baltimore, information regarding participation
      in regular, leisure-time activity (defined as 30 minutes of activity, 5 days per
      week), time spent walking on the job, and distance walked to and from work was
      assessed from 365 adults (69% women). Regular, leisure-time activity
      participation was 18% for men and 16% for women. When the definition of physical
      activity participation was broadened to include: (1) spending over half the day
      walking at work; (2) walking at least 10 blocks to and from work; as well as (3)
      regular, leisure-time activity, 41% of men and 38% of women were active. These
      data suggest that, while a small percentage of African Americans participate in
      regular physical activity, a substantial percentage are regularly active when non
      leisure-time activity is assessed. To accurately characterize overall
      participation, physical activity derived from a variety of sources, including
      transportation and work-related activity, should be assessed.

PMID- 9591203
TI  - Local reinvention of the CDC HIV prevention community planning initiative.
AB  - The Centers for Disease Control and Prevention (CDC), in coordination with 65
      states, cities, and territories, implemented HIV prevention community planning
      beginning in 1994. This large scale innovation in public health planning has
      involved tens of thousands of professionals and community residents. Though a
      single case study, Michigan provides a strong test of the implementation of this
      national prevention planning model because of the state's decentralized approach
      to HIV prevention community planning involving several hundred residents. A
      decentralized approach to community planning promises to maximize participation
      and the sharing of leadership as well as obstacles to community planning. Here,
      the CDC Guidance for community planning is contrasted with empirical observation
      of implementation in Michigan. We conclude that the high expectations for a
      decentralized approach to HIV prevention community planning can be best achieved
      when a distinction is drawn between information-seeking tasks and decision-making
      tasks. We recommend that information-seeking tasks be centrally coordinated, and
      that decision-making tasks be decentralized, to most fully achieve the potential
      of HIV prevention community planning.

PMID- 9591204
TI  - Teaching public health practitioners about health communication: the MPH
      curriculum experience.
AB  - The dissemination of health information to the public often occurs through the
      mass media. Media strategies as a component of behavior change assume knowledge
      of communication theories and methods by public health practitioners. We surveyed
      the curricula of 52 accredited graduate programs leading to the Master's in
      Public Health (MPH) degree to assess their communication component. Graduate
      bulletins for admission year 1996 were examined for public health mission
      statement, goals and objectives of the MPH training program, and for course
      titles. Courses were identified as having a communication focus if the terms
      communication, information, marketing or media were used in the title. There were
      a total of 82 communication courses offered, with 65 courses in 26 Schools of
      Public Health (SPH), 13 courses in 18 Community Health and Preventive Medicine
      departments (CHPM), and 4 courses in 8 Community Health Education departments
      (CHE). The difference in mean number of health communication courses was
      significant by type of MPH program (p < 0.003) with SPH offering an average of 3
      courses, CHPM departments offering an average of 1 course, and CHE offering an
      average of 0.5 course. The distribution of communication courses ranged from 10
      courses to 0 courses per program. Seven SPH offered 3 or more communication
      courses, whereas 5 SPH offered no health communication courses in the MPH
      curriculum. These data point to a shortcoming in the training of MPH students in
      health communication theory and skills as ascertained by course titles in
      graduate bulletins.

PMID- 9591205
TI  - Consistency in maintaining contact with HIV-related service providers: an
      analysis of the AIDS Cost and Services Utilization Study (ACSUS).
AB  - Patients (n = 1949) infected with HIV were recruited for the AIDS Cost & Service
      Utilization Survey (ACSUS) from ten U.S. cities and administered face to face
      interviews at three month intervals over an 18 month period from March 1, 1991 to
      August 31, 1992. The interview was designed to obtain information at each wave of
      data collection on the use of the following services: ambulatory care,
      hospitalization, emergency room use, support groups/counseling, drug and alcohol
      treatment, and dental care. Patients were found to be highly consistent in their
      patterns of utilization across time, regardless of the service in question. Of
      the patients who reported using an emergency room (ER) at Time 1, 52% also
      reported using an ER during the next three months later at Time 2. Of those who
      reported having been hospitalized during the Time 1 reporting period, almost 58%
      reported a hospitalization again at Time 2. Next, use of a service at Time 6 (n =
      1404, 72.2%) was regressed onto whether the person received the service at Time 2
      and the personal, financial, and medical variables. Except for dental services,
      utilization of a service one year in the past (Time 2) was the strongest
      predictor of Time 6 use. The findings indicated that the one factor consistently
      related to service use within this sample is a factor (as opposed to education,
      race, or even insurance) that is amenable to intervention: previous use of that
      service. The individuals studied established patterns of service utilization that
      are of reasonably long duration once they began use of a service. This continuity
      of care becomes more critical as the initiation of treatments begins with the
      diagnosis of HIV rather than AIDS. Findings suggest that HIV outreach efforts be
      targeted to increasing early use of medical and behavioral services in ambulatory
      care settings.

PMID- 9591206
TI  - Accessibility of cigarettes to minors in suburban Cook County, Illinois.
AB  - This study assessed the problem of under age sale of cigarettes, educated vendors
      about the law restricting the sale of tobacco to minors, and determined the
      effectiveness of a vendor education intervention. Twenty-one teen volunteers, 14
      to 17 years in age, attempted to purchase cigarettes in suburban Cook County from
      over-the-counter merchants and vending machines. Of the 347 vendors that were
      checked, the minors were successful in 37.2% of their attempts to purchase
      cigarettes. After information was sent to each vendor about the State of Illinois
      law, follow up visits were made to all the vendors who were willing to sell
      cigarettes to the minors during the first visits. Approximately 50% of the
      vendors were again willing to sell cigarettes to minors. This study's findings
      suggest that minors can easily purchase cigarettes in suburban Cook County. The
      education intervention component of the study had a limited but promising effect
      on compliance rates of the vendors.

PMID- 9591208
TI  - Height, weight, height velocity of primary school population sample in Campania
      region.
AB  - Aim of this study was to plot height, weight and height velocity values of
      primary school civic population of Portici and Ercolano, Campania towns, on
      Tanner's charts in order to verify the overlapping of percentile distribution. On
      May 1994 height and weight were measured in 3504 children (1735 boys and 1769
      girls, aged 5.4-16.1 years, mean age = 8.6 years) from the 1st, 2nd and 5th year
      of primary schools in Portici and Ercolano. One year later, on May 1995, we
      remeasured and reweighed 1583 (781 boys and 802 girls, aged 6.4-14.2 years, mean
      age = 9.6 years) out of total children and we calculated height velocity (HV).
      The height and weight profiles of our population sample show that children in
      Portici and Ercolano are taller and fatter than those measured by Tanner and
      Whitehouse 25-30 years ago. The calculation of body mass index (BMI) confirmed
      that 30% of total children were obese. Furthermore, the evaluation of one-year HV
      revealed a clear improvement of linear growth. Our data suggest that Tanner and
      Whitehouse charts should be updated, and it should be useful to elaborate also
      height, weight and HV standards derived from present-day population.

PMID- 9591207
TI  - Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues.
AB  - An altered control of the mechanisms involved in cell proliferation and
      programmed cell death (apoptosis) might play an important role in parathyroid
      tumorigenesis. We evaluated by immunohistochemistry the expression of bcl-2 and
      p53 proteins, as markers of apoptosis control, and MIB-1, as marker of cell
      proliferation, in a series of normal and neoplastic parathyroid tissues. The
      specimens were 33 normal parathyroids, 43 parathyroid adenomas and 3 parathyroid
      carcinomas. Results were scored as positive when more than 1% of cells were
      stained for MIB-1 and p53, and more than 10% for bcl-2. All normal parathyroids
      showed numerous bcl-2 positive cells (> or = 80%), low proliferation rate (MIB-1)
      and no p53 protein expression. Twenty-four (55%) adenomas were bcl-2 positive; in
      16 of these the number of positive cells was high (> 50%) and immunoreactivity
      was diffusely distributed within the adenoma; 8 cases showed a zonal staining
      pattern, in which groups of stained cells were surrounded by negative cells.
      Nineteen adenomas (45%) and all carcinomas were bcl-2 negative. A high
      proliferative rate (MIB-1) was found in all carcinomas and 4 adenomas (9%); all
      MIB-1 positive adenomas were bcl-2 negative. p53 was negative in all specimens.
      No significant differences in serum calcium and intact PTH levels nor in tumor
      size were found between bcl-2 negative and bcl-2-positive and MIB-1-positive and
      MIB-1-negative adenomas. An inverse, but not statistically significant (p = 0.06)
      correlation was observed between the percentage of bcl-2 positive cells and serum
      calcium level in parathyroid adenomas. In conclusion, parathyroid adenomas are a
      heterogeneous group of lesions in which the pattern of bcl-2 and MIB-1 protein
      expression ranges between that of normal parathyroid (bcl-2 positivity and MIB-1
      negativity) and that of parathyroid carcinoma (bcl-2 negativity and MIB-1
      positivity). The question of whether the finding of the MIB-1 positive-bcl-2
      negative phenotype identifies a subgroup of clinically more aggressive adenomas
      remains to be established.

PMID- 9591209
TI  - Endocrine mechanisms of stress-induced DHEA-secretion.
AB  - Acute psychological stress of a first time parachute jump stimulated DHEA and
      cortisol secretion in healthy volunteers. A significant shift from cortisol to
      DHEA occurred during this stress exposure. This effect was more pronounced in
      subjects receiving the beta-adrenoceptor antagonist propranolol prior to the
      jump. In contrast, infusion of epinephrine (0.10 microgram/kg/min) or
      norepinephrine (0.15 microgram/kg/min) for 20 min neither affected DHEA plasma
      levels nor the DHEA/cortisol ratio. However, pretreatment with propranolol
      resulted in a significant increase of the DHEA/cortisol ratio upon infusion of
      the beta-adrenoceptor agonist epinephrine. These data demonstrate that during
      acute psychological stress stimulation of adrenal steroid release is accompanied
      by a shift towards DHEA. Augmentation of this effect by beta-adrenoceptor
      blockade indicates a beta-adrenoceptor-dependent mechanism affecting DHEA
      release.

PMID- 9591210
TI  - The effect of hormone replacement therapy in postmenopausal women on urinary C
      telopeptide and N-telopeptide of type I collagen, new markers of bone resorption.
AB  - To analyze the inhibitory effect of hormone replacement therapy (HRT) on bone
      resorption, we measured urinary excretion of C-telopeptide (CTX) and N
      telopeptide (NTX) of type I collagen as new markers of bone resorption and
      assessed their correlation with bone mineral density, in comparison with urinary
      pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and hydoxyproline (Hpr). CTX and
      NTX, in addition to Pyr, D-Pyr, and Hpr, in urinary samples from 33
      postmenopausal women with climacteric symptoms who were treated with 0.625 mg
      conjugate equine estrogen and 2.5 mg medroxyprogesterone acetate for 12 months
      were measured using ELISA for each telopeptide. Bone mineral density in the
      lumbar spine was also measured by dual energy X-ray absorptiometry. Similar to
      Pyr, D-Pyr, and Hpr, urinary excretions of CTX and NTX significantly decreased
      during the continuous administration of conjugate equine estrogen and
      medroxyprogesterone acetate for 12 months. The magnitudes of the reduction of CTX
      and NTX were significantly greater than those of Pyr, D-Pyr, and Hpr. CTX and NTX
      correlated well with Pyr, D-Pyr, and Hpr, and there was a good correlation
      between CTX and NTX. Unlike Pyr, D-Pyr, and Hpr, the pretreatment values of CTX
      and NTX correlated negatively with bone mineral density at baseline. These
      results suggest that, among the markers for bone resorption, the changes in CTX
      and NTX could be greater than those in Pyr, D-Pyr, and Hpr during HRT in
      postmenopausal women.

PMID- 9591211
TI  - Stromal IGF-II messenger RNA in breast cancer: relationship with progesterone
      receptor expressed by malignant epithelial cells.
AB  - In breast cancer, insulin-like growth factor II (IGF-II) is stromal in origin and
      is considered an important regulator of tumour epithelium growth. The presence of
      progesterone receptor (PR) is expression of an intact oestrogen regulatory
      pathway of breast malignant epithelial cells and represents a parameter of cell
      differentiation in breast cancer. In this study we have examined the relationship
      between IGF-II mRNA expression and ER, PR content in 75 breast cancer. Formalin
      fixed paraffin-embedded tissue sections were used to preserve histological
      details. IGF-II mRNA was evaluated by in situ hybridisation method and ER, PR by
      immunohistochemistry. IGF-II mRNA was scored semi-quantitatively: 2.6% breast
      tumour specimen expressed no IGF-II mRNA, 46.7% had low levels of expression (IGF
      II-) and 50.7% had moderate or high IGF-II mRNA content (IGF-II+). IGF-II mRNA
      was found in the stroma fibroblasts surrounding malignant lesions and no signal
      was detected in malignant epithelial cells. In contrast, ER and PR were expressed
      only by neoplastic epithelial cells and no immunoreactivity was found in the
      stroma: 50/75 (66.6%) breast cancer specimens were positive for ER (ER+) and 35
      (46.6%) for PR (PR+). Both, IGF-II mRNA and PR were directly correlated with the
      stromal proliferation (p < 0.05 and p < 0.001, respectively). No relationship was
      found between IGF-II RNA and ER. In contrast 24/35 (73.5%) PR breast cancer
      tissues were IGF-II+ (p < 0.01) and a strong correlation was found between
      epithelial PR immunostaining and stromal IGF-II mRNA content (p < 0.003). Our
      data indicate that in breast cancer IGF-II mRNA is generally expressed by stromal
      cells and ER and PR by epithelial cancer cells, and that IGF-II mRNA expression
      is strongly related with both percentage and staining intensity of PR+ epithelial
      cancer cells. These data support the hypothesis that IGF-II produced by the
      fibroblasts may exert a paracrin effect on malignant epithelium regulating its
      differentiation.

PMID- 9591212
TI  - Serum levels of dimeric activin A are not a marker of placental tumors in the
      course of chemotherapy.
AB  - The aim of the present study was to evaluate whether serum activin A levels may
      represent, in addition to intact human chorionic gonadotrophin, a marker of
      placental tumors in the course of chemotherapy. Serial determinations of serum
      levels of activin A were performed in women with hydatidiform mole (n = 2) or
      choriocarcinoma (n = 3). Serum activin A levels were measured by using a new
      specific two-site enzyme immunoassay (EIA) able to detect the dimeric, bioactive,
      form of the protein. Serum hCG concentrations in samples taken after evacuation
      before starting chemotherapy were greater than in healthy non-pregnant women (p <
      0.001) and decreased following chemotherapy. Activin A serum levels in women with
      trophoblastic disease after evacuation were significantly higher than in healthy
      non-pregnant women, but chemotherapy did not significantly affect circulating
      levels. No correlation was found between changes of activin A and total hCG serum
      concentrations. Measurement of activin A by ELISA in presence of persistent molar
      tumor does not seem to be of clinical interest in the follow-up of disease,
      resulting activin A concentrations after chemotherapy in the range of values
      occurring throughout menstrual cycle. These evidences suggest that hCG
      determination is still the most valid for follow-up, because only intact hCG
      could detect the persistence of trophoblast tissue.

PMID- 9591213
TI  - Circulating levels of cardiac natriuretic peptides (ANP and BNP) measured by
      highly sensitive and specific immunoradiometric assays in normal subjects and in
      patients with different degrees of heart failure.
AB  - Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)
      levels increase in patients with heart failure with the progression of clinical
      symptoms and with the deterioration of hemodynamics; consequently, assay methods
      for these peptides may be useful in the follow-up of cardiac patients. Non
      competitive immunoradiometric assay (IRMA) methods for ANP or BNP do not
      generally require preliminary extraction and/or purification of the plasma
      sample, and so may be more suitable than competitive immunoradiometric assay
      (RIA) methods for the routine assay of plasma peptide concentrations. We
      evaluated the analytical characteristics and clinical usefulness of two IRMAs for
      plasma ANP and BNP, to verify whether these methods may be considered suitable
      for the follow-up of patients with heart failure. Both methods are based on the
      solid-phase sandwich IRMA system, which uses two monoclonal antibodies prepared
      against two sterically remote epitopes of peptide molecule; the first antibody
      was coated on the beads solid-phase and the second was radiolabeled with 125I.
      Blood samples were collected from a brachial vein in ice-chilled disposable
      polypropylene tubes containing aprotinin and EDTA after the patient had rested
      for at least 20 min in the recumbent position. Plasma samples were immediately
      separated by centrifugation and stored at -20 C until assay. The IRMA methods
      showed a better sensitivity and a wider working range sensitivity (about 2 ng/l)
      than those of RIA methods. Moreover, the normal range found with these methods
      (ANP = 16.1 +/- 8.6 ng/l, 5.2 +/- 2.8 pmol/l, BNP = 8.6 +/- 8.2 ng/l, 2.5 +/- 2.4
      pmol/l) was similar to that generally reported using the most accurate methods,
      such as the other IRMAs or RIAs, using a preliminary extraction and purification
      of plasma samples with chromatographic procedures. Our results obtained in
      patients with different degrees of heart failure indicate that plasma ANP and BNP
      increase with the progression of clinical symptoms (NYHA class) (ANOVA p <
      0.0001). Indeed, circulating levels of ANP (R = -0.701, no. = 86) and BNP (R = 
      0.745, no. = 55) were significantly (p < 0.0001) and negatively correlated with
      the left ventricular ejection fraction values. Furthermore, a close curvilinear
      regression (R = 0.960, no. = 215) was found between ANP and BNP values, because
      plasma BNP progressively increases more than plasma ANP in patients with
      different stages of heart failure. In conclusion, IRMA methods are preferable for
      the measurement of plasma ANP and BNP for experimental studies and routine assay
      because they are more practicable, sensitive and accurate than RIA procedures.
      Finally, BNP assay appears to be better than ANP for discriminating between
      normal subjects and patients with different degrees of heart failure.

PMID- 9591214
TI  - Isolated premature thelarche and thelarche variant: clinical and auxological
      follow-up of 119 girls.
AB  - Age of thelarche presentation, breast evolution, growth and puberty patterns were
      retrospectively evaluated in 119 girls with premature thelarche (PT). Thelarche
      spontaneously presented before 2 yr of chronological age in 80% of girls and
      completely regressed in 60% of them. Breast regression was significantly more
      frequent in the patients with more precocious thelarche presentation. In 40% of
      the girls breast size did not significantly change during a follow-up period
      ranging from 12 to 134 months (40.6 +/- 32.5). Among the 38 girls who were
      followed up to an age greater than 8 yr, seven (18.4%) developed central
      precocious puberty (PP). These 7 patients who progressed into true PP were
      indistinguishable from girls with normal puberty for age of thelarche
      presentation, breast size, evolution and auxological features. On the contrary, a
      subgroup of patients (28.5%) with accelerated height velocity and/or bone age at
      diagnosis of PT showed an auxological pattern different from normally growing
      girls during a 3-yr follow-up, but they did not seem to have higher risk of
      progressing into precocious puberty. In conclusion, PT encompasses different
      clinical, and perhaps hormonal situations, therefore requiring careful clinical
      follow-up.

PMID- 9591215
TI  - Pituitary adenomas secreting large amounts of prolactin may give false low values
      in immunoradiometric assays. The hook effect.
AB  - Immunoradiometric assay (IRMA) for serum prolactin (PRL) measurement can give
      falsely low values, leading to unnecessary surgery in patients with
      prolactinomas. We studied clinical and biochemical features of patients with
      pituitary macroprolactinomas in whom plasma PRL levels had been underestimated
      due to the so-called "high dose PRL hook effect". This phenomenon was observed in
      four (14.2%) out of 28 patients with pituitary macroadenomas (13 macroadenomas)
      and 15 non-functioning macroadenomas) reffer during one-year period. Undiluted
      median (range) PRL levels were 11.3 (3.0-48.7), 983.9 (194.4-1959.4), and 96.9
      (66.6-147.7) micrograms/l in patients with non-functioning macroadenomas,
      macroprolactinomas and the hook effect adenomas, respectively. In all patients
      assay was performed after serum dilution, and only in patients with the hook
      effect the median PRL levels increased significantly to 5795.0 (2097.2-12722.2)
      micrograms/l. The mean age at diagnosis was 38 +/- 6.5, 45 +/- 6, and 53 +/- 3
      yr, for the patients with the hook effect, macroprolactinoma and non-functioning
      adenoma, respectively. Males were predominant (75%) in the hook effect adenoma
      group. Patients with the hook effect macroprolactinomas were all treated
      successfully with dopamine agonists, and all patients had significant shrinkage
      of the tumor mass (more than 50% shrinkage). In conclusion, this study suggests
      that patients with high dose PRL hook effect are generally younger, more
      frequently males with very large pituitary adenomas (grade III-IV according to
      Hardy). It is necessary, whenever performing IRMA for serum prolactin
      measurement, to dilute samples routinely (1:1 and 1:10 dilutions) in every
      patient with pituitary tumor.

PMID- 9591216
TI  - Hyperfunctioning differentiated thyroid carcinoma.
AB  - A case of functioning plurifocal papillary carcinoma causing a clinical condition
      of hyperthyroidism is presented. Histologically, the carcinoma presented a
      dominant macrofocal nodule of an approximately 5 cm diameter, surrounded by
      chronic thyroiditis. Its occurrence in a patient under 20 years of age within a
      hot area in the thyroid bed and the lack of histological findings of hyperplastic
      tissue led the authors to consider this a rare case of hyperfunctioning
      differentiated thyroid carcinoma, and not a pure association of hyperthyroidism
      and carcinoma. Autonomously functioning thyroid nodules that are differentiated
      carcinomas are extremely rare with only 18 such cases reported in literature.
      While in the past it was commonly believed that a hot nodule is unlikely to be
      malignant, the possibility of an hyperfunctioning carcinoma should not be
      overlooked.

PMID- 9591217
TI  - Lymphocytic hypophysitis in a patient with Graves' disease.
AB  - A case of lymphocytic hypophysitis is described in a patients with Graves'
      disease and diabetes mellitus. The 62-year-old man was admitted to hospital with
      the complaints compatible with hyperthyroidism in April 1993. His medical
      history, physical examination, thyroid function tests, thyroid scintigraphy and
      thyroid ultrasonography revealed Graves' disease. The patient had also suffered
      from diabetes mellitus for three years. After this, the patient's progress was
      not monitored for two years. The patient presented himself again in September
      1995 with complaints of hypothyroidism, hypogonadism and hypoadrenalism. Hormonal
      investigation showed panhypopituitarism. A magnetic resonance imaging of the
      pituitary gland disclosed an enlarged pituitary and a thickened infundibulum. The
      high intensity signal of the neurohypophysis was absent. Transsphenoidal
      hypophysectomy was performed which revealed a grey-white, relatively avascular
      pituitary mass. Histology showed diffuse infiltration of the anterior pituitary
      by numerous lymphocytes. The neurohypophysis also showed evidence of lymphocytic
      infiltration. On the basis of these findings we suggest that lymphocytic
      hypophysitis may be associated with Graves' disease.

PMID- 9591218
TI  - PEI treatment of autonomous thyroid nodule (ATN) and Graves' disease.

PMID- 9591219
TI  - Multiple sclerosis: assessment of disability and disability scales.
AB  - Attempting to measure the impact of multiple sclerosis (MS) on the individuals
      patients has become a major issue stimulated by both the emergence of new
      therapeutic agents and the increasing demand to incorporate the patient's
      perspective. Disability has been the main focus. Recently, new disability scales
      have been developed and generic scales evaluated in an attempt to replace or
      complement the constantly used and much criticized Expanded Disability Status
      Scale (EDSS). There is, however, the growing realization that it is important to
      incorporate broader aspects of disease input such as are contained within the
      concepts of health-related quality of life. Current scales in this area are
      limited in either their scientific soundness and/or clinical usefulness, and it
      may be appropriate to consider the development of a new MS-specific measure of
      disease impact for use in clinical trials.

PMID- 9591220
TI  - Behcet's disease and the nervous system.
AB  - Behcet's disease is a multisystem inflammatory disorder with unknown aetiology.
      It is a disease of young adults with a more severe course in males subjects. Its
      prevalence is high in the Mediterranean basin and Japan and has been linked with
      human leucocyte antigen B5 (HLA-B5) in those countries. According to the
      diagnostic criteria formed by the International Study Group, recurrent oral
      ulceration is a prerequisite, with two more typical symptoms or signs.
      Neurological involvement is one of the most devastating manifestations of
      Behcet's disease. The involvement is either caused by primary neural parenchymal
      lesions (neuro-Behcet) or secondary to major vascular involvement (vasculo
      Behcet). The course is relapsing-remitting, secondary progressive or primary
      progressive. The most commonly involved area is the brain stem, with additional
      symptoms or signs, hemispherical involvement with mental changes being the most
      common. Intracranial hypertension, usually owing to dural sinus thrombosis, has a
      special place in Behcet's disease. The most common clinical findings are
      pyramidal signs. Sensory symptoms or signs are much less frequent, and hemianopia
      and higher cortical function disturbances as well as pure cerebellar syndrome are
      rare features. Cerebrospinal fluid usually has a high protein content and/or
      pleocytosis. Notably, in the acute period most patients have lesions shown by
      magnetic resonance imaging (MRI) extending from the brain-stem to diencephalic
      structures. Differential diagnosis from multiple sclerosis can be difficult in
      patients with hemispheric white matter MRI hyperintensities. Immunosuppressives
      are used in treatment.

PMID- 9591221
TI  - Alteration of early components of the visual evoked potential in amyotrophic
      lateral sclerosis.
AB  - Evoked potentials were recorded in three different visual experiments in 14
      patients with amyotrophic lateral sclerosis (ALS) and 14 matched control
      subjects. Control subjects' evoked potentials (EPs) were characterized by an
      initial positivity in the 90-140 ms range (P1) at the temporo-occipital site.
      This component was absent from the group average of the ALS patients as well as
      the individual patients' EPs. As the P1 is known to emanate from inferior
      occipito-temporal areas, this finding provides electrophysiological evidence for
      a cortical involvement in ALS including visual areas.

PMID- 9591222
TI  - Radiological evidence of subclinical dysphagia in motor neuron disease.
AB  - Dysphagia in motor neuron disease (MND) may lead to dangerous complications such
      as cachexia and aspiration pneumonia. Functional evaluation of the oropharyngeal
      tract is crucial for identifying specific swallowing dysfunctions and planning
      appropriate rehabilitation. As part of a multidisciplinary study on the treatment
      of dysphagia in patients with neuromuscular diseases, 23 MND patients with
      different degrees of dysphagia underwent videofluoroscopy,
      videopharyngolaryngoscopy and pharyngo-oesophageal manometry. The results of the
      three instrumental investigations were analysed in order (1) to define the
      pattern of swallowing in MND patients complaining of dysphagia; (2) to evaluate
      whether subclinical abnormalities may be detected; and (3) to assess the role of
      videofluoroscopy, videopharyngolaryngoscopy and manometry in the evaluation of
      MND patients with deglutition problems. Correlations between the instrumental
      findings and clinical features (age of the patients, duration and severity of the
      disease, presence and degree of dysphagia) were also assessed. The results of our
      study showed that: (1) The oral phase of deglutition was compromised most often,
      followed by the pharyngeal phase. (2) In all patients without clinical evidence
      of dysphagia, subclinical videofluoroscopic alterations were present in a pattern
      similar to that found in the dysphagic group. (3) Videofluoroscopy was the most
      sensitive technique in identifying oropharyngeal alterations of swallowing.
      Impairment of the oral phase, abnormal pharyngo-oesophageal motility and
      incomplete relaxation of the upper oesophageal sphincter were the changes most
      sensitive in detecting dysphagia. Videofluoroscopy was also capable of detecting
      preclinical abnormalities in non-dysphagic patients who later developed
      dysphagia. Practical guidelines for the use of instrumental investigations in the
      assessment and management of dysphagia in MND patients are proposed.

PMID- 9591223
TI  - A kindred affected by cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL). A 2-year neuropsychological follow
      up.
AB  - We report a 2-year prospective neuropsychological study of five asymptomatic
      subjects with magnetic resonance imaging (MRI) abnormalities from an Italian
      kindred affected by cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL). These subjects completed tests for
      attention capacities, processing speed, abstract thinking, short-term memory,
      learning and constructional praxis. Seven normal subjects matched for age and
      education, belonging to the same pedigree and not having MRI hyperintensities
      were examined as controls. The results did not show significant differences
      between asymptomatic subjects and normal controls. Cognitive performance of
      asymptomatic subjects did not deteriorate during a 2-year follow-up. Our findings
      suggest that, at this stage of the disease process, the presence of diffuse
      leukoencephalopathy does not imply subtle cognitive defects.

PMID- 9591224
TI  - The effect of tolcapone on levodopa pharmacokinetics is independent of
      levodopa/carbidopa formulation.
AB  - Clinical pharmacology studies have shown that the catechol-O-methyltransferase
      inhibitor tolcapone increases the bioavailability area under the plasma
      concentration-time curve (AUC) and the plasma elimination half-life (t1/2) of
      levodopa. The objective of the study was to evaluate the pharmacokinetics of
      levodopa and 3-O-methyldopa (3-OMD) after coadministration of tolcapone 200 mg
      with levodopa/ carbidopa in the following doses: 100/10 mg, 100/25 mg, 200/20 mg,
      200/50 mg, 250/25 mg (all immediate-release) and 200/50 mg (controlled-release).
      Thirty healthy male volunteers were divided into four groups: three groups of 8
      and one group of 6. Participants in the first three groups received two
      formulations of levodopa/carbidopa. Each dose was administered on two occasions,
      once with tolcapone 200 mg and once with placebo (four-way crossover). In the
      fourth group, one formulation was given on two occasions, once with tolcapone 200
      mg and once with placebo (two-way crossover). Dosing days were separated by a 7
      day washout. The effect of tolcapone on levodopa and 3-OMD pharmacokinetics was
      found to be similar with all levodopa/carbidopa formulations. The absorption of
      levodopa was unaffected by tolcapone in all treatment groups and the maximum
      plasma concentration (Cmax) remained unchanged. When tolcapone was given with the
      immediate-release formulations, levodopa AUC increased by 60-90% and levodopa
      t1/2 by 20-60%. With tolcapone and the controlled-release formulation, AUC
      increased by 80% and t1/2 by 60%. With all levodopa/carbidopa formulations, 3-OMD
      Cmax decreased by 80% and AUC by 70% with tolcapone. The tolerability of all
      treatment combinations was similar. We conclude that adjunctive treatment with
      tolcapone should have similar levodopa-potentiating clinical effects, regardless
      of the levodopa/carbidopa formulation.

PMID- 9591225
TI  - Atypical ataxia telangiectasia with early childhood lower motor neuron
      degeneration: a clinicopathological observation in three siblings.
AB  - We report three brothers belonging to a consanguineous family and suffering from
      ataxia telangiectasia with severe early neurogenic amyotrophy. Pathological
      examination of the brain and spinal cord in one of them showed Purkinje cell loss
      with empty baskets and numerous axonal spheroids, dorsal column demyelination
      with astrocytic proliferation and severe anterior horn cell degeneration. We
      consider these pathological findings to be related to Louis-Bar disease. Anterior
      horn cell changes may be one of the early pathological features in ataxia
      telangiectasia.

PMID- 9591226
TI  - CCNU overdose during PCV chemotherapy for anaplastic astrocytoma.

PMID- 9591227
TI  - Steroid-dependent anti-Hu negative paraneoplastic encephalomyelitis and small
      cell lung carcinoma.

PMID- 9591228
TI  - A second family with hereditary motor and sensory neuropathy with deafness,
      mental retardation and absence of large myelinated fibres, detected in the same
      geographic area as the first family.

PMID- 9591229
TI  - Plasma beta-carotene, retinol, and alpha-tocopherol levels in relation to
      glycemic control of children with insulin-dependent diabetes mellitus.
AB  - Plasma beta-carotene, alpha-tocopherol and retinol were measured in 15 female and
      5 male children with insulin-dependent diabetes mellitus (IDDM), and the
      correlations with plasma hemoglobin A1c (HbA1c) and fructosamine were analyzed.
      Twelve female and 8 male children served as age-matched controls. The plasma beta
      carotene and alpha-tocopherol levels of the IDDM children were significantly
      higher than those of the control children, but there were no differences in
      plasma retinol or total lipid levels. The plasma beta-carotene level, beta
      carotene/retinol ratio and beta-carotene/total lipids ratio each showed
      significant correlations with serum HbA1c and fructosamine in all subjects
      studied. Similarly, the plasma alpha-tocopherol level and alpha-tocopherol/total
      lipids ratio were correlated with these indexes of glycemic control. These
      findings suggest certain mechanisms may exist to prevent lipid peroxidation and
      vascular complications in IDDM patients.

PMID- 9591230
TI  - Histochemical observation and cellular distribution of ascorbic acid in persimmon
      leaves.
AB  - This study was carried out to resolve the discrepancy of data for the proportion
      of ascorbic acid and dehydroascorbic acid in persimmon leaves at the final stage
      of the season and to clarify their cellular distributions using histochemical and
      biochemical techniques. Fresh persimmon leaves were collected and used on July
      31, September 5 and October 7, 1996. Ascorbic acid and dehydroascorbic acid in
      subcellular fractions were determined by the HPLC method that was found to be the
      most reliable for separation. The percent of dehydroascorbic acid in the total
      leaves was found to be almost constant (between 32 and 37%) in all preparations
      tested. In all preparations, more than 90% of the ascorbic acid and
      dehydroascorbic acid was found in the soluble fraction. The histochemical
      detection of ascorbic acid and an electron micrograph of persimmon leaf cells
      showed that the reactive color, after the reduction of silver nitrate under
      acidic conditions, in the leaves of all three preparations was mainly found on
      the face side of columned-type palisade parenchyma cells where chloroplasts were
      not rich and large vacuoles were seen. On the inner side of the palisade
      parenchyma cells where chloroplasts were the richest, only weak color development
      was observed. This study demonstrates that the percent of dehydroascorbic acid in
      persimmon leaves did not exceed 40% at least until October 7. It also shows that
      in persimmon leaf cells, ascorbic acid is mainly localized in the cytosol of
      palisade parenchyma tissue cells where large vacuoles are seen.

PMID- 9591231
TI  - Separative determination of ascorbic acid analogs contained in mushrooms by high
      performance liquid chromatography.
AB  - Analogs (6-deoxyascorbic acid, erythroascorbic acid, and associated glycosides)
      of L-ascorbic acid (AA) contained in mushrooms were allowed to react with
      hydrazine to form osazones, and the conditions for separative determination by
      HPLC using a Zorbax SIL column were examined. Separation was started using
      solvent system 1 (ethylacetate/n-hexane/acetone/acetic acid, 50:50:1:1, v/v) as
      the mobile phase, and switching after 15 min to solvent system 2
      (ethylacetate/acetone/acetic acid, 100:1:1, v/v). Detection was performed by
      absorbance at 500 nm. Because these analogs showed different formation rates for
      osazone, calibration curves were prepared for each substance. The recovery rate
      in the load test was 93-105%. By this method, AA and the analogs contained in
      eight species of edible mushrooms have been determined. The results revealed
      that: (1) the main constituents of all mushrooms are AA analogs rather than AA
      itself; (2) only one species contained AA in a very small amount (2 mumol/kg);
      (3) the types of AA analogs present differed according to the species of
      mushrooms, and (4) the total amount of AA analogs was between ca. 100-500
      mumol/kg (2-9 mg per 100 g, converted to AA). In addition, a new AA analog was
      found in Pleurotus ostreatus and identified as 5-O-(alpha-D-xylopyranosyl)-D
      erythroascorbic acid in structural analyses by NMR and other methods.

PMID- 9591232
TI  - Dietary protein as a factor affecting vitamin B6 requirement.
AB  - Rats were fed 20 or 70% casein diets with varying amounts of vitamin B6 (B6), and
      the B6 content and B6-dependent enzymatic activity in their tissues were examined
      to determine the minimum requirement of B6 for animals subjected to different
      levels of dietary protein (i.e., 20%: 0, 1.45, 2.90, 5.80 mg pyridoxine (PN)/kg
      diet; 70%: 0, 2.90, 5.80, 8.70 mg PN/kg diet). B6 requirements for the rats were
      almost met in the 1.45 mg PN/kg 20% casein diet and the 2.90 mg PN/kg 70% casein
      diet when judged from the hepatic B6 content. However, almost twice the PN was
      required in both 20 and 70% casein diets when judged from PLP-enzymatic activity.
      The content of B6 vitamers in plasma appeared to be most sensitive to B6 status,
      though the satisfactory level is not known. It was confirmed that, in any case
      tested, a high-protein diet increased the requirement of B6.

PMID- 9591233
TI  - Comparison of glucose and fat as energy sources in peripheral parenteral
      nutrition in rats.
AB  - Glucose is usually chosen as the energy source for total parenteral nutrition.
      However, the optimal glucose:fat ratio for peripheral parenteral nutrition has
      not been examined sufficiently. We compared glucose:fat ratios in hypocaloric
      nutrition. Male SD rats were given hypocaloric parenteral nutrition (approx. 190
      kcal/kg/d) for 5 d after laparotomy. The hypocaloric solutions used contained 0,
      33, 50, 67 or 100% of the non-protein energy in the form of fat. Body weight
      change, nitrogen balance, organ weights, and hepatic, splenic and plasma
      biochemistries were assessed. Body weight increase in the 67 and 100% fat groups
      was significantly greater than that in the 0% fat group. Nitrogen balance was the
      same in all groups. Hepatic glycogen content was significantly lower in the 100%
      fat group than that in the 0% fat group. The weight of epididymal fat deposits
      was significantly lower in the 0% fat group than in the 50 and 67% fat groups. On
      the other hand, tissue triglyceride content and plasma lipid levels in the 100%
      fat group were significantly higher than in the 0% fat group, and were also
      higher than in the control group. It is suggested that combinations of glucose
      and fat have sparing effects on body fat and hepatic glycogen. Combinations of
      glucose and fat as non-protein energy sources were superior to glucose or fat
      alone for hypocaloric parenteral nutrition.

PMID- 9591234
TI  - The effect of dietary fatty acid manipulation on phagocytic activity and cytokine
      production by peritoneal cells from Balb/c mice.
AB  - Previous studies have demonstrated that dietary lipid manipulation may modify
      immune response by affecting lymphocyte proliferation, phagocytosis, cytokine
      production, etc. In this paper, we investigated the effect of olive oil (OO) on
      the phagocytic activity and cytokine production by murine peritoneal cells. These
      results were compared with those obtained from mice fed diets containing
      sunflower oil (SO) or hydrogenated coconut oil (HCO). Balb/c mice were divided
      into three groups and fed diets containing 15% by weight of either OO, SO or HCO
      for 5, 15, 30, 60 or 90 d. Phagocytic activity and interleukin-1 (IL-1)
      production were increased in OO-fed mice as compared to the other groups. On the
      contrary, no significant differences were observed in the levels of tumor
      necrosis factor (TNF) production, although the levels of this cytokine were
      slightly increased in mice fed the OO diet. These observations suggest that OO is
      able to modify the immune response and therefore, it may be used as an
      immunomodulatory agent.

PMID- 9591235
TI  - Disaccharidase activity in rat cecum and colon with hyperplasia induced by
      maltitol or glucomannan.
AB  - The existence of disaccharidases and an enzyme that hydrolyzes maltitol were
      investigated in the large intestine of rats. In addition, the properties of
      disaccharidases were studied in the cecum and colon with hyperplasia induced by
      the ingestion of nondigestible carbohydrates such as maltitol and glucomannan.
      Maltase activity was detected in the cecal and colonic mucosa of rats fed a
      regular diet, although it was a very low level as compared with that in the small
      intestinal mucosa. Maltitol hydrolysis was notably lower in the cecum and colon
      than in the small intestine. The Km of maltose was 5.56 mM in the small intestine
      and 5.59 mM in the cecum, while that in the colon was 2.56 mM. The Vmax of
      maltose was at very low levels in the cecum (0.38 mumol/mg protein/h) and colon
      (0.37 mumol/mg protein/h) in comparison with that in the small intestine (30.3
      mumol/mg protein/h). With regard to the maltitol hydrolyzing enzyme, Km and Vmax
      were 2.00 mM and 2.51 mumol/mg protein/h in the small intestine, respectively. Km
      and Vmax in the cecum and colon could not be measured because the level was too
      low. The tissue weights of the cecum and colon increased significantly in both
      the maltitol (p < 0.01, p < 0.05) and glucomannan (p < 0.01, p < 0.05) groups in
      comparison with that of the control group. The specific activity of maltase
      decreased significantly in the small intestine of the maltitol (p < 0.05) and
      glucomannan (p < 0.01) groups. However, maltase activity in the cecum and colon
      was not lowered by maltitol ingestion, although it decreased significantly in the
      cecum of the glucomannan group (p < 0.01). Sucrase activity in the small
      intestine and cecum was decreased significantly by maltitol (p < 0.05, p < 0.01)
      or glucomannan (p < 0.01, p < 0.01) ingestion, whereas it was not decreased in
      the colon. Maltitol hydrolyzing activity did not decrease significantly in the
      small intestine of the maltitol group, although that in the cecum and colon was
      not measured exactly by the methods used here. These results demonstrate that
      disaccharidases exist in the cecal and colonic mucosa of rat, and that they are
      not induced even in the tissue with hyperplasia, which is caused by maltitol
      ingestion.

PMID- 9591236
TI  - Tumor growth inhibition and nutritional effect of D-amino acid solution in AH109A
      hepatoma-bearing rats.
AB  - We examined the inhibitional and nutritional effects of total parenteral
      nutrition (TPN) containing D-amino acids (D-phenylalanine, D-Phe; D-valine, D
      Val; D-leucine, D-Leu; D-methionine, D-Met) on tumor growth in AH109A hepatoma
      bearing rats. Five experimental groups were examined: a control amino acid
      solution group (control group), D-Phe group, D-Val group, D-Leu group and D-Met
      group. The analysis of tumor volume and weight revealed significant tumor growth
      inhibition in the D-Val group as compared with the control group. In the D-Val
      group, decreases of DNA and protein contents in the tumor tissues were also
      observed. The D-Leu and D-Met groups showed a tendency toward tumor growth
      inhibition. The protein content in the liver tissues of these two groups was
      significantly higher as compared with the control group. The DNA content in the
      liver tissue was also significantly higher in the D-Met group. The body weight
      including the tumor (on the final day of TPN) was significantly lower in the D
      Val group as compared with the control group, but there was no significant
      difference in the groups for body weights not including tumors (carcass body
      weight). The hematocrit and hemoglobin values, indicators of anemia, were
      significantly higher in the D-Val group as compared with the control group. From
      these results, regarding tumor growth inhibition, the D-Val solution had the
      strongest inhibitory effect with no negative influence on the host, and
      improvement of nutritional status was also suggested in the rats that received
      the D-Leu or D-Met solutions.

PMID- 9591237
TI  - Xenobiotic tolerance of primary cultured hepatocytes in rats fed a high-fat or
      high-protein diet.
AB  - The diet and nutritional status dominate a tolerance to environmental
      xenobiotics. In this study, the cytotoxic action of carbon tetrachloride (CCl4)
      and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), one of the dietary
      carcinogens, was investigated using primary cultured hepatocytes from rats fed a
      high-fat (23% corn oil) or high-protein (50% casein) diet for three weeks. Both
      chemicals showed strong cytotoxicity to hepatocytes, which was judged by
      measurement with the MTT-test and lactate dehydrogenase leakage test. A dietary
      effect on cytotoxicity was observed; hepatocytes from rats fed the high-protein
      diet were more susceptible to cytotoxicity than the cells from rats fed a
      standard diet. On the other hand, ureogenesis, as a cellular function of
      hepatocytes, was markedly decreased in the cells from rats fed the high-fat diet.
      These activities were affected in the CCl4-treated cells but not in the Trp-P-1
      treated cells. The same trend of both diet and chemical effects was observed in
      gluconeogenesis from fructose. We conclude that the hepatocytes from rats fed a
      high-protein diet have high susceptibility to the cytotoxicity of CCl4 and Trp-P
      1, but cytotoxicity was not related to the reduction of cellular functions.

PMID- 9591238
TI  - Effect of indigestible saccharides on B lymphocyte response of intestinal mucosa
      and cecal fermentation in rats.
AB  - The effects of water-soluble and -insoluble indigestible saccharides (IDS) on
      immune responses of the intestinal tract were studied. Male 4-week-old Sprague
      Dawley rats were fed for three weeks on diets containing several kinds of IDS at
      5%. The results revealed that the proportion of kappa-light chain and IgA
      presenting lymphocytes in small intestinal and cecal mucosa differed in increased
      number depending on the type of IDS. The response of colonic mucosa was not
      pronounced. The amounts of short-chain fatty acid (SCFA) and lactic acid in the
      cecal contents of the other test groups except the celfur group tended to be
      higher than those in the cellulose group, particularly in the lactulose group
      where many acids showed significant increases. The correlation between the
      proportion of kappa-light chain and IgA-presenting lymphocytes in the cecal
      mucosa and lactic acid in the cecal contents was significant, but that between
      the proportion of both lymphocytes and SCFA was not. Based on the above, we
      concluded that the oral administration of IDS induces the proliferation of kappa
      light chain and IgA-producing B lymphocytes in small intestinal and cecal mucosa,
      but the degree of response differs depending on the type of IDS. It is thus
      suggested that IDS are involved in the intestinal immune system of rats.

PMID- 9591239
TI  - Effects of soy protein isolate (SPI) and casein on the postprandial lipemia in
      normolipidemic men.
AB  - To elucidate the effects of soybean protein and casein on postprandial lipemia,
      oral fat load tests were performed before and 3 weeks after the administration of
      soy protein isolate (SPI) and casein supplement to normolipidemic men. Eleven
      normolipidemic male subjects on otherwise identical controlled diets were
      assigned to either a 20 g/d soy protein isolate (SPI) dietary supplement or a
      casein dietary supplement for three weeks in a crossover design. Fat load tests
      with 40 g/m2 of bovine milk fat were carried out before and after 3 weeks on the
      experimental dietary supplements. Fasting plasma concentrations of lipids and
      apolipoproteins were not significantly different from baseline levels before or
      after the administration of SPI or casein supplemented diets. Neither SPI nor
      casein supplement affected the fasting plasma concentrations of lipids and
      apolipoproteins. The areas under the incremental curve (AUIC) of triglyceride
      (TG) and remnant-like particles triglyceride (RLP-TG) after both experimental
      diets were not significantly different from those before the experimental diets.
      However, the AUIC of remnant-like particles cholesterol (RLP-C) showed a tendency
      (p = 0.07) to decrease after administration of the diet supplemented with SPI
      than before the diet. The AUIC of RLP-C was significantly (p < 0.05) lower after
      the diet supplemented with SPI than after administration of the diet supplemented
      with casein. These results suggest that 3 weeks of 20 g/d SPI dietary supplement
      favorably affects the postprandial remnant lipoprotein response as compared to
      the casein dietary supplement.

PMID- 9591240
TI  - Dietary linoleic acid alters alpha-amino-beta-carboxymuconate-epsilon
      semialdehyde decarboxylase (ACMSD), a key enzyme of niacin synthesis from
      tryptophan, in the process of protein expression in rat liver.
AB  - alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) [EC
      4.1.1.45] is a key enzyme of niacin synthesis from tryptophan. In this study, we
      examined whether dietary linoleic acid alters the protein expression of ACMSD in
      rat liver. Antibody against rat liver ACMSD was prepared by injecting mice with
      the purified enzyme. With the use of this polyclonal antibody and analysis by two
      dimensional electrophoresis, we studied the mechanism by which the level of liver
      ACMSD activity was varied in rats fed a linoleic acid diet. In the rats fed a
      dietary linoleic acid (L), ACMSD protein levels in the liver were strongly
      suppressed as compared with the rats fed a fat-free diet (FF). These results
      suggest that the expression level of ACMSD might be modulated by linoleic acid or
      their metabolites.

PMID- 9591241
TI  - Transcriptional regulation of rat calbindin expression during development
      determined by bacterially expressed protein.
AB  - Calbindin-D9k expression in intestinal mucosal cells reveals a specific pattern
      during development in rats. It shows a low basal level in suckling and adult
      rats, but after weaning at 21 d of age, increases to three times that of the
      basal level for several days only, around 24 d. We attempted to clarify whether
      the regulation of developmental change was at the transcriptional or post
      transcriptional level. The calbindin-D9k protein and mRNA concentrations during
      pre- and postweaned development were determined by Western blot and Northern blot
      analysis, respectively, and compared with calcium binding activity by 45Ca. For
      Western blot analysis, a corresponding antibody was raised in rabbit using a
      bacterially expressed fusion protein, glutathione S-transferase (GST, EC
      2.5.1.18), and calbindin-D9k. Calbindin-D9k cDNA was linked to a GST gene within
      a molecule of vector plasmid and a fusion protein was expressed in Escherichia
      coli. There were significant (p < 0.001) correlations between calbindin-D9k
      protein, mRNA concentrations and calcium-binding activity: r = 0.90 for protein
      vs. mRNA, r = 0.93 for protein vs. binding activity and r = 0.95 for mRNA vs.
      binding activity. These results indicate that calbindin-D9k expression during
      postnatal development is regulated at the transcriptional level.

PMID- 9591242
TI  - Characteristics of energy metabolism in males with mental retardation.
AB  - To characterize the energy metabolism in individuals with mental retardation
      (MRs), we measured energy cost at several physical activity levels (basal,
      supine, sitting, standing, and walking at 30, 50 and 70 m/min), maximal oxygen
      consumption (Vo2max), and body composition in 23 male MRs and the same number of
      volunteer male controls. Both groups were individually matched for age, body
      height, and body weight. Energy cost was measured by the Douglas bag technique.
      The recently developed sulfur hexafluoride (SF6) dilution technique was employed
      for measuring body composition. In addition, 3-dimensional accelerometry was used
      for evaluating body movements, and plasma indices of macronutrients were also
      measured. The energy cost of MRs, when sitting, standing, and walking at 30 and
      50 m/min, was significantly higher than that of controls (p < 0.05), while the
      basal and resting metabolic rates were similar in both groups. Vo2max was
      significantly lower (p < 0.05) in MRs than controls. Accelerometry demonstrated
      excessive movement by MRs, which may explain their higher energy cost of
      exercise. In contrast, no significant difference was observed in percent body fat
      or lean body mass. Concentrations of plasma total cholesterol, triacylglycerols
      and albumin were significantly lower in MRs as compared with the controls. Our
      findings suggest that MRs are burdened with an energy metabolism less economical
      than non-MRs. Limited physical activity in their daily life may be the cause.
      These characteristics of MRs' energy metabolism should be considered for planning
      their proper dietary schedules and physical activity programs.

PMID- 9591243
TI  - Inhibitory effect of ethanol administration on beta-alanine-2-oxoglutarate
      aminotransferase (GABA aminotransferase) in disulfiram-pretreated rats.
AB  - Ethanol in the presence of disulfiram (N,N,N',N'-tetraethylthiuram disulfide, an
      inhibitor of aldehyde dehydrogenase) inhibited liver beta-alanine-oxoglutarate
      aminotransferase (beta-AlaAT I) activity yet activated tyrosine aminotransferase
      (TAT) in weanling rats in vivo. The effect on beta-AlaAT I was followed by the
      inhibitory expression of beta-AlaAT I mRNA. The beta-AlaAT I activity was reduced
      with a pseudo-first-order profile with time, and the half-life was calculated to
      be 12.3 +/- 0.83 h with the rate constant (Kd) of 0.056 +/- 0.004 h-1. The
      synthesis of beta-AlaAT I in rat liver was estimated to be 1.56 x 10(-10) mol/g
      of wet tissue per hour at a steady state. A combination of ethanol and disulfiram
      also reduced beta-alanine-pyruvate aminotransferase (beta-AlaAT II) activity to
      60% of the control after 24 h.

PMID- 9591244
TI  - Protein-nutritive assessment of sake lees obtained by brewing from liquefied
      rice.
AB  - Sake lees obtained by brewing from liquefied rice were deprived of water and
      alcohol by lyophilization, and then examined for nutritional availability with
      the aid of proximate food analysis, amino acid analysis and animal experiment.
      Freeze-dried sake lees powder was comprised of 44.6% protein, 37.4% carbohydrate,
      2.5% fat, 6.7% fiber, 1.8% ash and 7.2% moisture (alcohol < 0.1%), of which the
      nutritive value (amino acid score) was estimated as 89.6 when compared with the
      amino acid requirements for preschool children (FAO/WHO/UNU, 1985). Sake lees
      protein had been, however, appreciably improved in the limiting amino acid
      "lysine" relative to polished rice protein. As a result of an animal experiment,
      the rats fed a 50% sake lees powder diet proved to be equal in growth to those
      fed a 20% casein (control) diet, although the former diet had to be supplemented
      with vitamins and minerals, which were in shortage as compared to the control
      diet. On the other hand, the feeding of sake lees powder was effective in
      lowering the serum triacylglycerol concentration. Accordingly, sake lees powder
      can be assessed as a favorable candidate for not only protein-rich but also
      hypolipidemic provisions.

PMID- 9591245
TI  - Supplementation of Bifidobacterium longum to a high-fat, low-calcium diet lowers
      cytolytic activity of fecal water in rats injected with 1,2-dimethylhydrazine
      dihydrochloride.
AB  - The effects of supplementing Bifidobacterium longum SBT 2928 and Lactobacillus
      acidophilus SBT 2062 to a high-fat, low-calcium diet on bile acid concentration,
      fatty acid concentration, cytolytic activity and intestinal alkaline phosphatase
      (ALP) activity of fecal water in rats injected with and without 1,2
      dimethylhydrazine dihydrochloride (DMH) were examined. Male Wistar rats at 8
      weeks of age were fed a diet containing 18% coconut oil, 2% corn oil and 0.1%
      calcium for 15 d. Lyophilized cultures were supplemented to test diets at a
      concentration of 1%. The feeding of a high-fat, low-calcium diet elevated the
      bile acid concentration, cytolytic activity and ALP activity of fecal water as
      compared to the AIN-76A diet, whereas the fatty acid concentration was not
      changed. None of the cultures had any effect on these parameters. Furthermore, 8
      week-old rats were given a single subcutaneous injection of DMH at 40 mg/kg body
      weight, and fed the same diets for 15 d. The DMH injection had no effect on the
      bile acid concentration but increased the fatty acid concentration and cytolytic
      activity of fecal water. In contrast, ALP activity was lower in the DMH-treated
      rats than in the non-treated rats. The ingestion of B. longum lowered cytolytic
      activity but had no effect on the bile acids, fatty acids and ALP activity of
      fecal water. L. acidophilus had no effect on these parameters.

PMID- 9591246
TI  - The future belongs to the bioentrepreneur.

PMID- 9591247
TI  - Bioentrepreneurship around the world.

PMID- 9591248
TI  - Growing an international biotechnology company.

PMID- 9591249
TI  - Europe discovers bioentrepreneurship.

PMID- 9591250
TI  - Some thoughts on bioentrepreneurship.

PMID- 9591251
TI  - Factors for success in biotechnology: then and now.

PMID- 9591252
TI  - Five "C's" of successful startups.

PMID- 9591253
TI  - The three pillars of bioentrepreneurship.

PMID- 9591254
TI  - Business models for the bioentrepreneur.

PMID- 9591255
TI  - Venturing into drug discovery.

PMID- 9591256
TI  - A bill of rights for bioentrepreneurs.

PMID- 9591257
TI  - Molecular medicine and information-based targeted healthcare.

PMID- 9591258
TI  - Biotechnology's metamorphosis into a drug discovery industry.

PMID- 9591259
TI  - The power of genomics to transform the biotechnology industry.

PMID- 9591260
TI  - Optimizing the impact of genomics on drug discovery and development.

PMID- 9591261
TI  - The evolving role of collaboration in biotechnology.

PMID- 9591262
TI  - In silico drug discovery: tools for bridging the NCE gap.

PMID- 9591263
TI  - Cementing links between industry and the university.

PMID- 9591264
TI  - Becoming a bioentrepreneur.

PMID- 9591265
TI  - The startup balancing act: hiring the right talent.

PMID- 9591266
TI  - Building the board of directors.

PMID- 9591267
TI  - Scenes from an unlikely marriage: building a corporate culture in biotechnology.

PMID- 9591268
TI  - For success, focus your strengths.

PMID- 9591269
TI  - The patenting challenges of gene discovery.

PMID- 9591270
TI  - Making your genes come true.

PMID- 9591271
TI  - Navigating biotechnology's new fiscal opportunities.

PMID- 9591272
TI  - Snaring a venture capital investment.

PMID- 9591273
TI  - Quantifying the dream: valuation approaches in biotechnology.

PMID- 9591274
TI  - When to access the capital markets.

PMID- 9591275
TI  - How do you measure "success" in a biotechnology company?

PMID- 9591276
TI  - Biotechnology mergers and acquisitions.

PMID- 9591277
TI  - Where have all the investors gone?: the case for consolidation.

PMID- 9591278
TI  - Public sector funding in the UK.

PMID- 9591279
TI  - Motor and somatosensory conduction time between the cortex and the Erb point in
      patients suffering from cervical spinal stenosis and tumour.
AB  - Motor and sensory conduction time between the cortex and the Erb point were
      examined in patients with cervical cord compression. Patients were divided into
      two groups: the compression was caused either by cervical extramedullary tumour
      (9 cases), or by cervical spondylosis or herniated disc (16 cases). In response
      to median nerve stimulation, pathological somatosensory evoked potentials were
      recorded in 66% of the patients suffering from tumour and in 60% of the patients
      suffering from spondylosis. All of the patients disclosed pathological motor
      evoked potentials. On the basis of these observations it could be concluded that,
      in cases of cervical spinal cord compression, the involvement of the motor system
      could be more reliably detected than that of the sensory system with
      electrophysiological methods.

PMID- 9591280
TI  - Maleic acid is an aldose reductase inhibitor.
AB  - The effects of a series of dicarboxylic acids on aldose reductase activity were
      investigated in a crude enzyme preparation obtained from ocular lenses of the
      swine. Of the compounds examined, maleic acid inhibited aldose reductase in a
      pronounced manner and in a concentration-dependent fashion (IC50 value of 83.0 +/
      1.4 mM). Saturation experiments revealed non-competitive kinetics with a Ki
      value of 64.9 +/- 1.7 mM. The present results suggest that, at higher doses,
      maleic acid might have some implication for the treatment of diabetic
      complications.

PMID- 9591281
TI  - Mediator substances of the pineal neuronal network of mammals.
AB  - In addition to receptor-type pinealocytes, the mammalian pineal organ contains
      small and large neurons and ependymal/glial cells as well. Axons of pinealocytes
      form synaptic ribbon-containing axo-dendritic synapses on large secondary pineal
      neurons and/or terminate as neurohormonal endings on the basal lamina of the
      vascular surface of the organ. The small pineal neurons were found to be gamma
      aminobutyric acid (GABA)-immunoreactive, while large secondary neurons and
      pinealocytes contained immunoreactive amino acids (glutamate and aspartate).
      Glutamate accumulated presynaptically in pinealocytic axon terminals on large
      secondary neurons and in the axons of these neurons. Glutamate immunoreactive
      axons of pineal neurons were traced via the pineal tract to the habenular
      nucleus. Axons containing granular vesicles and coming from extrapineal perikarya
      are glutamate immunoreactive as well. Aspartate and GABA are also present in some
      of the myelinated axons, supposedly pinealopetal in the pineal tract.

PMID- 9591282
TI  - Effect of catecholaminergic lesions of medial prefrontal cortex on regulation of
      body weight and glucose preference.

PMID- 9591283
TI  - Role of accumbens cholinergic interneurons in the maintenance of body weight.

PMID- 9591284
TI  - Glial reactions to lesions in neural transplants: a preliminary study.

PMID- 9591285
TI  - Dorsal root origin of axonal growth cones: regenerative synapto-neogenesis in the
      upper spinal dorsal horn of primates.

PMID- 9591286
TI  - Projections of the medial and superior vestibular nuclei to the brainstem and
      spinal cord in the rat.

PMID- 9591287
TI  - Effects of different types of anticholinesterase agents on in vivo hippocampal
      population spikes in rats.

PMID- 9591288
TI  - Double immunohistochemical study on paraventricular efferents to autonomic
      centers.

PMID- 9591297
TI  - [Annual survival rates in lacunar stroke in relation to neurological status, risk
      factors and applied anti-aggregation treatment].
AB  - Lacunar stroke accounts for 20-25% of all ischaemic strokes. It is believed that
      the prognosis in this stroke is relatively good, with annual mortality being 9.8%
      to 11.3%. In the analysis of the Warsaw Stroke Register this mortality was much
      higher--about 25%. The purpose of the present study was to assess the factors
      increasing the probability of death in lacunar stroke based on a one-year follow
      up of 113 patients (67 males and 48 females), mean age 67.3 +/- 11.2 treated at
      the II Department of Neurology, Institute of Psychiatry and Neurology. The total
      one-year mortality was 23%. In the group of patients dying in that year
      hypertension was found in 88% and diabetes in 27%, while in the surviving group
      these diseases were found in 72% and 18% respectively. The differences between
      groups were not significant. Considering the effect of other risk factors (age,
      fitness status assessed with modified Barthel index) it was demonstrated that the
      risk of death increased with increasing age (relative risk 1.03, 95% CI 1.001
      1.05) and with the degree of dependence on the help of others, Barthel index < 60
      (RR = 1.49.95%, CI 1.24-1.66). In the analysis of the effect of antiaggregation
      treatment the mortality was lower in aspirin-treated patients (300 mg daily) with
      cumulated annual survival rate 79.8 as compared to the not treated patients in
      whom it was 58.2. The difference was not significant, probably due to small
      number of cases.

PMID- 9591298
TI  - [Piracetam treatment in ischemic stroke].
AB  - The increase of interest in piracetam in the treatment of stroke has been noticed
      lately. The reason of that is the unique double-action of this drug which depends
      on: 1. its effect on vascular system, and 2. improving of the metabolic process
      in a nerve cell. The purpose of our work was the evaluation of the therapeutic
      action of piracetam in comparison with other drugs, which are applied in treating
      stroke. 171 patients were examined, and piracetam was given to 40 of them. The
      effects of the treatment were evaluated after 14 days of using piracetam in dose
      of 12.0 g i.v. The authors estimate, that this drug is efficient in ischaemic
      stroke. However, its definite superiority over other drugs has not been firmly
      stated.

PMID- 9591299
TI  - [The assessment of tumor necrosis factor (TNF) alpha and interleukin (IL)-1 beta
      levels in cerebrospinal fluid (CSF) and serum in patients with purulent
      meningitis].
AB  - The purpose of this work was to detect the concentration of cytokines--tumor
      necrosis factor (TNF)-alpha and Interleukin (IL)-1 beta in cerebrospinal fluid
      (CSF) and serum, their diagnostic and prognostic usefulness among patients with
      purulent meningitis. 25 patients of Centre of Parasitic Diseases and
      Neuroinfections hospitalized with diagnosis or suspicion of purulent meningitis
      were studied. The patients were divided into two groups: I-12 persons with
      diagnosis of purulent meningitis and group II-13 controls where suspicion of
      meningitis was excluded during clinical procedure. The cytokines were detected by
      immunometric assay. This examination was performed twice--before and after
      treatment. In group I-patients with purulent meningitis, TNF-alpha and IL-1 beta
      CSF concentrations were significantly higher in comparison with group II. After
      treatment the concentrations of cytokines did not show significant differences
      between group I and II. In acute phase of meningitis correlations between CSF
      concentration of TNF-alpha and IL-1 beta and other indexes of inflammation in
      CSF: pleocytosis, concentration of protein and glucose were found. The serum
      concentrations of the cytokines were many times lower than in CSF. The detection
      of TNF-alpha and IL-1 beta CSF concentration can be used to estimate the efficacy
      of therapy and regression of inflammation in the central nervous system.

PMID- 9591300
TI  - [Comparative assessment of treatment efficacy with lamotrigine (Lamictal)
      together with valproate and/or carbamazepine in patients with refractory
      epilepsy].
AB  - For the study 17 patients aged 26-55 years were qualified after ineffective
      treatment with carbamazepine and/or valproate for simple partial, complex partial
      or secondary generalized seizures. The criterion of resistance to treatment was
      the occurrence of four or more seizures monthly. The treatment with lamotrigine
      was successful in 9 (52%) cases, with reduction of seizures by at least 50%. In 2
      cases the seizure activity in EEG became normal. In 8 cases the addition of
      lamotrigine was ineffective and the drug was discontinued (in one case due to
      allergic rash and in one the cause was toxic hepatocellular damage).

PMID- 9591301
TI  - [Assessment of early treatment results with antineoplaston AS2-1 in subacute
      sclerosing panencephalitis].
AB  - A tentative treatment with Antineoplaston AS2-1 was carried out in a group of 16
      patients with subacute sclerosing panencephalitis (SSPE). Most patients were in
      phase II of SSPE (after Jabbour) with mean disease duration 6.4 months. Their age
      ranged from 13 to 28 years. They were given for 6 months 15 capsules of
      Antineoplaston AS2-1 and 6 tablets of isoprinosine daily. Despite that treatment
      progression was observed of the disturbances of higher nervous functions, less so
      of motor functions. The treatment had no effect on MRI results, EEG and
      antimeasles antibodies levels. No adverse effects were observed.

PMID- 9591302
TI  - [Segmental motor conduction time for abductor of the fifth finger muscle: methods
      and normative values].
AB  - Electrical stimulation of the ulnar nerves (60 nerves) and magnetic stimulation
      of the roots (C7) and motor cortex were performed on 30 normal controls. The
      muscle responses and F wave (peripheral stimulation) were recorded from abductor
      digiti minimi muscle (60 muscles). The parameters of examined potentials were
      measured and the central, root, peripheral motor conduction times were estimated.
      The normative values were established as well as formulae of linear regression
      within the observed correlations with height. The method may be used for
      electrophysiological diagnosis of patients with motor pathway impairment at the
      different levels.

PMID- 9591303
TI  - [The effect of early decompression on the extent of changes in spinal cord
      microcirculation in experimental traumatic injury to the cord in rabbits].
AB  - The purpose of the study was the assessment of the effect of compression of the
      spinal cord after traumatic injury on spinal microcirculation disturbances and
      the evaluation in what degree early decompression of the cord reduces the degree
      of these changes. The experimental study was carried out on 20 rabbits. The
      injury to the cord was produced at the Th9-Th10 level with simultaneous
      compression causing vertebral canal narrowing by 1/3 of its width. The assessment
      was based on the results of microangiographic qualitative and quantitative
      studies. The animals were divided into 4 groups depending on the duration of cord
      compression 2, 4, 6 and 12 hours. In each group microcirculation studies were
      done 12 hours after decompression. Prolonged compression was found to increase
      the extent of microcirculation disturbances, which were most pronounced after 6
      hours of compression. In the group of 12-hour compression microcirculation
      improvement was observed near the focal lesion. It is concluded that possibly
      early decompression up to 6 hours after trauma can reduce the degree of secondary
      damage caused by ischaemia.

PMID- 9591304
TI  - [The effect of prolonged spinal cord compression on the extent of morphological
      changes in experimental spinal cord injury in rabbits].
AB  - The analysis of early spinal cord decompression influence on the extent of
      morphological and microvascular changes after traumatic cord injury was the
      subject of this study, carried out on Polish-breed rabbits divided into two
      groups. Microvascular changes were evaluated in the first group of 20 animals and
      morphological changes in the second group of 36 rabbits. The injury causing
      paraplegia was performed at D9-D10 level by Allen method modified. Every group
      was subdivided into 4 subgroups depending on the duration of cord compression 2,
      4, 6 and 12 hours. Fragments of cord were taken for examination 12 hours after
      decompression, from sites 0.5, 1.0 and 1.5 cm distant from the injury level.
      Histopathological analysis was performed by light and electron microscopy and for
      the analysis of microcirculation with microangiography the Gorkiewicz method was
      used. Great changes were found in nerve fibres, vascular endothelium and
      microcirculation. The most pronounced lesions were found in the subgroup with 6
      hour compression, in the form of haemorrhage, central necrosis and oedema within
      and around axona as well as destruction of myelin sheaths. Early decompression
      (within 6 hours) can reduce the extent of morphological and vascular changes.

PMID- 9591305
TI  - Childhood Crohn's disease and the efficacy of enteral diets.
AB  - Enteral diets, both elemental and, more recently, polymeric (whole protein), are
      used as primary therapy in Crohn's disease and can induce disease remission
      without the concomitant use of immunosuppressive drugs. Controlled trials
      comparing enteral nutrition with corticosteroid therapy have given mixed results
      but suggest, at least in children, that they are as effective as corticosteroids
      in inducing remission. There is no clear consensus as to which dietary therapy is
      best. Elemental diets do not seem to be superior to polymeric whole protein-based
      diets, although further work is necessary. The effect of enteral diets does not
      seem to be related to the site of intestinal inflammation. Enteral nutrition is
      particularly appropriate in children and adolescents with Crohn's disease,
      improving nutrition and promoting growth and pubertal development, and avoiding
      the systemic toxicity of corticosteroid therapy. Most centers will use it as a
      first line of treatment. Supplementary enteral nutrition after primary therapy
      and remission induction may be associated with the prolongation of remission and
      promotion of linear growth. Pathways by which enteral diets may affect mucosal
      inflammation are discussed. Enteral diets may inhibit intestinal immune responses
      by reducing the number of cytokine-producing cells. Enteral nutrition may also
      boost immunosuppressive pathways, which then endogenously suppress ongoing
      inflammation. Enteral diets may promote epithelial healing and
      reepithelialization of Crohn's ulcers and may also reduce the bacterial load in
      the small bowel.

PMID- 9591306
TI  - The metabolic effect of dodecanedioic acid infusion in non-insulin-dependent
      diabetic patients.
AB  - Dodecanedioic acid (C12) is an even-numbered dicarboxylic acid (DA). Dicarboxylic
      acids are water-soluble substances with a metabolic pathway intermediate to those
      of lipids and carbohydrates. Previous studies showed that contrary to other DAs,
      very low amounts of C12 are lost with urine. The effects of 46.6 mmol of C12
      intravenous infusion for 195 min on blood glucose levels were investigated in
      five patients with non-insulin-dependent diabetes mellitus (NIDDM), with a good
      metabolic compensation, and in five healthy volunteers matched for gender, age,
      and body mass index. Blood samples were taken every 15 min for a period of 360
      min to measure glucose, insulin, C-peptide, ketone bodies, and free fatty acid
      (FFA) levels, and 24-h urine samples were collected to measure C12 and urea
      excretion. Plasma and urinary C12 concentrations were determined by high-pressure
      liquid chromatography (HPLC). Indirect calorimetry was continuously performed
      both basally and during the study period. The average 24-h urinary excretion of
      C12 was 6.5% versus 6.7% of the administered dose, respectively, in NIDDM
      patients and in healthy controls. The area under the curve (AUC) values of plasma
      C12 were 279.9 +/- 42.7 mumol in NIDDM patients and 219.7 +/- 14.0 mumol in
      controls (P = ns). Plasma glucose levels significantly decreased in NIDDM
      patients during C12 infusion (from 7.8 +/- 0.6 to 5.4 +/- 0.8 mM at the end of
      the study period, P < 0.05). Lactate plasma concentration decreased in NIDDM
      patients from 3.5 +/- 0.2 to 1.5 +/- 0.1 mM (P < 0.001), whereas blood pyruvate
      increased at the end of the experimental session from 26.0 +/- 11.6 to 99.5 +/-
      14.9 microM (P < 0.01). Free fatty acids decreased in diabetic patients from the
      beginning until the end of C12 infusion, although this difference did not reach
      statistical significance. No significant increase was found between basal and
      final values in VO2 consumption and in the values of nonprotein respiratory
      quotient in both groups of subjects examined. The experimental data indicate that
      C12 infusion decreases plasma glucose levels in NIDDM patients to normal range
      without influencing plasma insulin levels. The balance between pyruvate and
      lactate was affected by C12 infusion only in diabetics patients. C12 might
      represent a fuel substrate immediately available for tissue energy requirements,
      especially in conditions such as diabetes mellitus in which glucose metabolism is
      impaired.

PMID- 9591307
TI  - Alterations in intestinal barrier function do not predispose to translocation of
      enteric bacteria in gastroenterologic patients.
AB  - Bacterial translocation from the intestinal lumen has been demonstrated in
      humans. Three mechanisms have been suggested to explain the phenomenon: altered
      intestinal barrier function, bacterial overgrowth, and impaired host defense. The
      aim of this study was to determine whether changes in intestinal barrier function
      assessed by measurement of intestinal permeability and morphology were associated
      with alteration in bacterial translocation. Intestinal permeability was assessed
      in 43 patients by the lactulose/L-rhamnose test with a 5-h urine collection.
      Mucosal atrophy was assessed from the villus height-to-mucosal thickness ratio in
      small-bowel biopsies. Bacterial translocation was determined by microbiologic
      analysis of harvested mesenteric lymph nodes. No significant differences were
      apparent in the incidence of bacterial translocation in patients with normal
      permeability (5 [23%] of 22 patients translocated) compared with patients with
      increased permeability (4 [19%] of 21 patients translocated). Similarly, no
      correlation was apparent between the incidence of bacterial translocation and the
      index of villus atrophy. The degree of villus atrophy failed to correlate with
      gastrointestinal permeability. These data suggest that the incidence of bacterial
      translocation is not related to increased intestinal permeability or mucosal
      atrophy.

PMID- 9591308
TI  - Does the Pall TNA-1E parenteral nutrition admixture filter retain Malassezia
      furfur?
AB  - Malassezia furfur has been shown to be capable of survival and reproduction in
      fat emulsions for parenteral nutrition, and this has been suggested as the source
      of serious systemic infections in neonatal intensive care units. Under conditions
      of use similar to those found in neonatal practice, the Pall TNA-1E filter was
      found to reliably retain this organism for up to 48 h.

PMID- 9591309
TI  - Effect of hepatic iron on hypercholesterolemia and hypertriacylglycerolemia in
      copper-deficient fructose-fed rats.
AB  - The purpose of this investigation was to establish whether plasma cholesterol and
      triacylglycerol(s) in copper deficiency can be increased or decreased by hepatic
      iron levels. Weanling male Sprague-Dawley rats were randomly divided into six
      dietary groups based on levels of dietary copper and iron. They were fed from
      weaning their respective diets for 6 wk. Forty percent of the copper-deficient
      rats fed a 15.7 mumol Fe/g diet died; 22% of those fed a diet containing 8.6
      mumol Fe/g died; and there were no deaths in the 3.4 mumol Fe/g diet group. Rats
      belonging to the group fed the high-iron diet also exhibited the highest levels
      of liver iron, liver glutathione, and plasma cholesterol and triacylglycerol(s)
      compared with those fed either the adequate or low levels of dietary iron. There
      was a direct correlation (r = 0.82 and 0.77, respectively) between levels of
      cholesterol and triacylglycerol(s) in plasma and hepatic iron concentrations.
      These results provide strong evidence that points to a major involvement of iron
      in the lipemia of copper deficiency. These data may be important to those
      individuals who consume large quantities of fortified iron foods and supplement
      with iron but whose intake of copper is suboptimal.

PMID- 9591310
TI  - Effects of a newly developed fat emulsion containing eicosapentaenoic acid and
      docosahexaenoic acid on fatty acid profiles in rats.
AB  - A new fat emulsion of symmetrical triacylglycerols, containing only
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was developed. The
      effects of this preparation on serum and liver fatty acid composition were
      investigated. Male Sprague-Dawley rats were fed a fat-free oral diet for 2 wk and
      were then divided into two groups. Seven rats were infused for 7 d with 1 mL of
      the new fat emulsion, which accounted for 1% of total caloric intake. The other 7
      rats received saline. Both groups of rats received a fat-free diet during the
      infusion. EPA and DHA decreased to one third to one fifth of normal value after 2
      wk on a fat-free diet. EPA and DHA of serum and liver remained at a low level in
      the control group throughout the study. But in the rats administered with the new
      fat emulsion, EPA and DHA increased rapidly and exceeded normal values in both
      serum and liver after 7 d of infusion. Decreased arachidonic acid with increased
      20:3n-9 resulted in the rise of the triene/tetraene (T/T) ratio to greater than
      0.4, indicating an n-6 essential fatty acid deficiency in the control rats. In
      the group administered the new fat emulsion, however, 20:3n-9 and total content
      of monounsaturated fatty acids decreased significantly, and the T/T ratio was
      less than than 0.4 in both serum and liver. In conclusion, the intravenous use of
      a newly developed fat emulsion containing EPA and DHA is useful in improving the
      EPA and DHA status of serum and liver without any harmful effects. Beneficial
      effects are expected in the modulation of inflammatory and stress response.

PMID- 9591311
TI  - The role of nitric oxide in hepatic metabolism.
AB  - Nitric oxide (NO) may regulate hepatic metabolism directly by causing alterations
      in hepatocellular (hepatocyte and Kupffer cell) metabolism and function or
      indirectly as a result of its vasodilator properties. Its release from the
      endothelium can be elicited by numerous autacoids such as histamine, vasoactive
      intestinal peptide, adenosine, ATP, 5-HT, substance P, bradykinin, and calcitonin
      gene-related peptide. In addition, NO may be released from the hepatic vascular
      endothelium, platelets, nerve endings, mast cells, and Kupffer cells as a
      response to various stimuli such as endotoxemia, ischemia-reperfusion injury, and
      circulatory shock. It is synthesized by nitric oxide synthase (NOS), which has
      three distinguishable isoforms: NOS-1 (ncNOS), a constitutive isoform originally
      isolated from neuronal sources; NOS-2 (iNOS), an inducible isoform that may
      generate large quantities of NO and may be induced in a variety of cell types
      throughout the body by the action of inflammatory stimuli such as tumor necrosis
      factor and interleukin (IL)-1 and -6; and NOS-3 (ecNOS), a constitutive isoform
      originally located in endothelial cells. Another basis for differentiation
      between the constitutive and inducible enzymes is the requirement for calcium
      binding to calmodulin in the former. NO is vulnerable to a plethora of biologic
      reactions, the most important being those involving higher nitrogen oxides (NO2
      ), nitrosothiol, and nitrosyl iron-cysteine complexes, the products of which (for
      example, peroxynitrite), are believed to be highly cytotoxic. The ability of NO
      to react with iron complexes renders the cytochrome P450 series of microsomal
      enzymes natural targets for inhibition by NO. It is believed that this mechanism
      provides negative feedback control of NO synthesis. In addition, NO may regulate
      prostaglandin synthesis because the cyclooxygenases are other hem-containing
      enzymes. It may also be possible that NO-induced release of IL-1 inhibits
      cytochrome P450 production, which ultimately renders the liver less resistant to
      trauma. It is believed that Kupffer cells are the main source of NO during
      endotoxemic shock and that selective inhibition of this stimulation may have
      future beneficial therapeutic implications. NO release in small quantities may be
      beneficial because it has been shown to decrease tumor cell growth and levels of
      prostaglandin E2 and F2 alpha (proinflammatory products) and to increase protein
      synthesis and DNA-repair enzymes in isolated hepatocytes. NO may possess both
      cytoprotective and cytotoxic properties depending on the amount and the isoform
      of NOS by which it is produced. The mechanisms by which these properties are
      regulated are important in the maintenance of whole body homeostasis and remain
      to be elucidated.

PMID- 9591312
TI  - Physiologic role of the complement system in host defense, disease, and
      malnutrition.
AB  - The role of the complement system as a system merging early-phase innate immunity
      with later-phase acquired immunity has been established. C3 is a key protein of
      the complement system. It is activated in four pathways: (1) the alternative
      pathway, (2) the mannan binding protein pathway, (3) the C-reactive protein
      pathway, and (4) the natural IgM pathway in innate immunity. It is also activated
      in (1) a classic pathway, i.e., through an antigen-antibody complex, and (2) by
      injured host cells in acquired immunity. Activation of C3 results in a variety of
      immunologic reactions such as immune adherence, phagocytosis, antibody response,
      cytolysis, inflammation, and killing of pathogenic microorganisms. Pathologic
      pictures of the complement system in various diseases were reviewed. Attention
      was focused on hypocomplementemia in the malnourished state. In humans and in
      experimental animals, reduced complement levels, especially of C3, were observed
      in relation to lowered host defense against infection. Hypocomplementemia
      improved after nutritional rehabilitation with a concomitant improvement of the
      clinical picture and recovery of host resistance. Enhancement of C3 levels in
      malnourished or well-nourished rats resulted in heightened resistance against
      bacterial infections. On the basis of these experimental and clinical
      observations, we obtained clues to prevent or treat a compromised host defense
      system in malnourished states.

PMID- 9591313
TI  - Continuous translocation of endotoxin and tumor necrosis factor translocation
      from the unused gut.

PMID- 9591314
TI  - Yeast infections on the neonatal unit: one cheer for parenteral nutrition
      admixture filters.

PMID- 9591315
TI  - The periodontal and bony aspects in the jaws in relation to home parenteral
      nutrition.

PMID- 9591316
TI  - Antibodies as predictors of insulin-dependent diabetes mellitus before the
      clinical onset.

PMID- 9591318
TI  - The use of lipid infusions in postoperative nutrition.

PMID- 9591317
TI  - The use of blood tests to detect alcohol as a cause of pancreatitis.

PMID- 9591319
TI  - Using resident assessment data to improve nutritional care in nursing homes: the
      power of information.

PMID- 9591320
TI  - The current state of home nutrition support in the United States.

PMID- 9591321
TI  - X-ray microscopic visualization of specific labeling of adhesive molecule CD36
      and cytoadherence by Plasmodium falciparum infected erythrocytes.
AB  - We investigated the cytoadherence of Plasmodium falciparum infected erythrocytes
      to target cells that express CD36 by soft x-ray microscopy. Using immunogold
      beads enhanced with silver, we localized CD36 on the surface of intact melanoma
      cells and throughout Triton extracted melanoma cells. We examined the orientation
      of parasites within erythrocytes that bound to target cells, and the interactions
      between the red cell membrane and the target cell, and we confirmed that
      fibrillar structures on the surface of melanoma and endothelial cells can be
      involved in the association between infected erythrocytes and melanoma cells or
      endothelial cells.

PMID- 9591322
TI  - Inhibitory effect of a marine microalgal polysaccharide on the telomerase
      activity in K562 cells.
AB  - An extracellular polysaccharide from marine microalga, dinoflagellate Gymnodinium
      sp. A3 (GA3), showed cytotoxicity to human myeloid leukemia K562 cells. We
      measured telomerase activity in K562 cells cultured with GA3 polysaccharide. 10.0
      micrograms/ml of GA3 polysaccharide inhibited the telomerase activity in the
      cells completely. Also, we found a decrease in expression of the catalytic
      subunit of protein phosphatase (PP) type 1, PP1 gamma 1, in K562 cells cultured
      with GA3 polysaccharide.

PMID- 9591323
TI  - Decrease of nuclear protein phosphatase 1 activity and induction of mitotic
      arrest and apoptosis by a marine microalgal polysaccharide in human myeloid
      leukemia U937 cells.
AB  - An extracellular polysaccharide, which we designate GA3P, produced from a marine
      microalga dinoflagellate Gymnodinium sp. A3, has been previously reported to
      induce apoptosis in lymphoid and myeloid cell lines. We found that the GA3P
      accumulates cells into the mitotic phase of the cell cycle and decreases nuclear
      protein phosphatase 1 (PP1) activity in a dose-dependent manner in myeloid
      leukemia U937 cells. Dose-dependent patterns in the decrease of nuclear PP1
      activity and in the accumulation of cells into mitotic phase or apoptotic status
      by the GA3P were concordant with each other, indicating that the decrease of
      nuclear PP1 activity at least mediates some of the etiological steps in
      development of mitotic arrest and apoptosis induced by the GA3P. In addition, the
      GA3P repressed the expression of protein levels of the PP1 catalytic subunit
      isoform PP1 gamma 1 gamma 1. We thus suggest that the decrease of nuclear PP1
      activity is due to down-regulation of the protein levels of the PP1 gamma 1.

PMID- 9591324
TI  - Increased polyploidy, delayed mitosis and reduced protein phosphatase-1 activity
      associated with excess copper in the Long Evans Cinnamon rat.
AB  - Until now, it is not known whether copper hepatotoxicity impairs mitosis.
      Enlarged hepatocytes with huge nuclei considered as polyploids are frequently
      observed in the Long Evans Cinnamon (LEC) rat which exhibits an abnormal
      accumulation of hepatic copper due to a defect in the gene homologous to human
      Wilson's disease gene responsible for intracellular copper delivery. This defect
      may lead to a abnormal mitotic progression in increased polyploidization and is
      associated with excessive hepatic copper. This study was designed to examine
      whether excess copper impairs mitotic progression and results in increased
      polyploidization using a model of LEC rat liver. Polyploidy was analyzed by flow
      cytometry. The rate of mitotic progression was investigated using the fraction of
      mitotic hepatocytes or a mitosis-specific phosphoprotein retained in
      regeneration. Nuclear protein phosphatase-1 (PP-1) activity essential to mitotic
      progression was measured. The effect of excess copper on incidence of polyploidy,
      the rate of mitotic progression and nuclear PP-1 activity was investigated using
      age- or copper overload-dependent changes in them in LEC rat, or genetic profile
      dependent changes of them in backcrosses. LEC rat liver showed an increase of
      polyploidy, a delay of mitotic progression, and a reduction of nuclear PP-1
      activity. These abnormal features concurred with increase of copper concentration
      accompanied by changes of age in LEC rats from 2 to 4 months of age, induced by
      dietary copper overload in LEC rat, or caused by single genetic defect in
      backcrosses. Excess copper impairs mitotic progression, resulting in increased
      polyploidization. Nuclear PP-1 activity is likely to be at least one of targets
      of copper hepatotoxicity leading to impairment of mitotic progression.

PMID- 9591325
TI  - Effect of 5-hydroxytryptamine on intracellular calcium dynamics in cultured rat
      vascular smooth muscle cells.
AB  - The present study elucidated the precise mechanism of 5-hydroxytryptamine (5-HT)
      induced increase of intracellular Ca2+ concentration ([Ca2+]i) in cultured
      vascular smooth muscle cells isolated from rat aortic media. [Ca2+]i was measured
      using fluorescent Ca2+ indicator, fura-2. 5-HT caused a dose-dependent increase
      in [Ca2+]i, which was completely inhibited by ketanserin. alpha-Methyl-5-HT had
      an equipotent effect to 5-HT. Diltiazem at 10 microM partially suppressed the 5
      HT-induced increase in [Ca2+]i. 5-HT also augmented Mn2+ influx, when monitored
      by Mn2+ quenching of fura-2 fluorescence. When extracellular Ca2+ (1.3 mM) was
      removed, a decrease in resting level and a small, transient increase in [Ca2+]i
      were observed. 5-HT stimulation also induced an increase in the production of
      inositol triphosphate. 5-HT-induced increase in [Ca2+]i was significantly, but
      partially inhibited by staurosporin and H-7. Phorbol 12-myristate 13-acetate
      induced an increase in [Ca2+]i, which was abolished by removal of extracellular
      Ca2+. 5-HT-induced increase in [Ca2+]i was not affected by the pretreatment with
      pertussis toxin (PTX), and was not accompanied by a change in cyclic AMP content.
      These results suggest that, in cultured rat aortic smooth muscle cells, 5-HT
      increases [Ca2+]i via 5-HT2 receptor subtype by inducing influx of extracellular
      Ca2+ partially through L-type voltage-dependent Ca2+ channel, as well as by
      mobilizing Ca2+ from its intracellular stores. Activation of protein kinase C may
      be positively involved in the regulatory mechanism of Ca2+ influx, but PTX
      sensitive G protein and cyclic AMP seem to be not involved.

PMID- 9591326
TI  - Cardioprotective effects of beraprost sodium against experimental ischemia and
      reperfusion as compared with propranolol and diltiazem.
AB  - We compared the cardioprotective effects during experimental ischemia and
      reperfusion of beraprost sodium (beraprost), a prostacyclin analog, with those of
      propranolol and diltiazem. Coronary perfused guinea-pig right ventricular free
      wall preparations were subjected to 30 min no-flow ischemia with or without
      drugs, followed by 60 min reperfusion without drugs. In control preparations,
      decrease in contractile force and increase in resting tension were observed
      during the no-flow period. On reperfusion, contractile force returned to less
      than 50% of preischemic values. Beraprost, at 0.1 microM, showed no inotropic
      effect under normoxic condition and during the no-flow period, but significantly
      enhanced the recovery of contractile force after reperfusion to about 80% of
      control values. Propranolol (30 microM) or diltiazem (10 microM) produced similar
      enhancement of recovery of contractile force after reperfusion, but these two
      drugs decreased the contractile force under normoxic conditions to less than 20%
      of control values. Thus, the cardioprotective effect of beraprost was different
      from those of propranolol and diltiazem in that it was not accompanied by
      cardiosuppressive effects.

PMID- 9591327
TI  - Effect of carboxy-PTIO, a nitric oxide scavenger, on the proliferation of murine
      hematopoietic progenitor cells in vitro.
AB  - We investigated the effect of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline
      1-oxyl 3-oxide (c-PTIO), a specific nitric oxide scavenger and a stable radical
      compound, on the proliferation of murine hematopoietic progenitor cells in vitro.
      The c-PTIO promoted colony formation by erythropoietin and either interleukin-6
      (IL-6) or the c-kit ligand/stem cell factor (SCF) in a methylcellulose culture,
      where the number of colonies increased 2.2-fold and 1.7-fold, respectively.
      During the addition of c-PTIO to the liquid cultures of murine bone marrow cells
      containing a combination of IL-6 and SCF, colony-forming cells in vitro (CFC) and
      the colony-forming unit in the spleen (CFU-S) increased about 1.8-fold and 1.7
      fold, respectively, higher than the control culture after 7 day of culture. When
      c-PTIO was added twice at days 0 and 2 during the culture, 3.6-fold and 1.7-fold
      increases over the control were observed in the number of CFC and CFU-S. These
      results suggest the possibility that c-PTIO regulates the proliferation and
      differentiation of hematopoietic stem/progenitor cells in vitro.

PMID- 9591328
TI  - Prevalence of factor V Leiden in African-Americans.
AB  - Factor V Leiden (FVL) refers to a mutation on the clotting factor, Factor V.
      Protein C is a factor involved in the fibrinolytic pathway. Activated protein C
      (APC) normally degrades activated Factor V. The presence of the Leiden mutation
      on Factor V makes this protein resistant to degradation by APC, leading to a
      hypercoagulable state. Previous studies reported a prevalence of FVL in various
      populations between 0-6% and absent in Africans. We studied two factor V alleles
      from one hundred random blood samples submitted for CBC. DNA was extracted, PCR
      was performed for wild-type allele and Leiden mutation with GH internal control
      for both reactions, and agarose gel electrophoresis was performed. Of 100
      samples, five were heterozygous for FVL, which is in accord with other reports.
      Interestingly, four of 70 samples (5.8%) from African-Americans were positive for
      the mutation. The study indicates an apparent prevalence of 5% in the Newark, New
      Jersey population, including African-Americans.

PMID- 9591329
TI  - G-protein activation and expression in lung injury.
AB  - Lung injury and repair are characterized by changes in the phenotypic and
      functional characteristics of parenchymal cells. It is not known to what extent
      these changes are regulated by alterations in total G-protein activity or
      expression of G-protein subfamilies. G-proteins (GTPases) are receptor-associated
      proteins that act as molecular switches for signal transduction pathways. They
      are involved in regulating ribosomal protein synthesis, transmembrane signaling
      of hormones and growth factors, cellular differentiation and proliferation and
      guiding organelle movement within cells. In this study, we validated, modified
      and optimized the experimental conditions needed to evaluate GTPase activity in
      the lung. We also measured changes in GTPase activity and the expression of G
      protein subfamilies in lungs undergoing paraquat lung injury. Total GTPase
      activity as well as the expression of Gi, Gs, and Go subfamilies demonstrated a
      sharp increase on day 1 after injury, a time previously shown to coincide with
      rapid cellular proliferation and increased protein synthesis. In contrast to the
      other subfamilies, expression of the alpha subunit of the Gs subfamily was more
      intense and sustained during the repair phase (day 14). These findings implicate
      G-proteins in general, and the Gs subfamily, in particular, in regulating
      cellular function during lung repair.

PMID- 9591330
TI  - [Medical behavior after colo-rectal cancer screening--comparison with that after
      stomach cancer screening].
AB  - Medical behavior for intensive examination after colo-rectal cancer screening was
      examined in comparison with that after stomach cancer screening. Examinees who
      were positive in colo-rectal or stomach cancer screening, provided by an
      Occupational Health Organization from April 1993 to March 1994, were monitored
      for their medical behavior through notifications from physicians. The main
      results were as follows: 1. The proportion of those with the notification from a
      physician after colo-rectal cancer screening was half of that after stomach
      cancer screening. 2. Among those notified the rate of those who undertook
      intensive examination by the end of 12 weeks after the screening was 79.7% for a
      colo-rectal site and 87.0% for the stomach. The time interval from the screening
      to the intensive examination for the colo-rectal site was significantly longer
      than that for stomach. 3. For colo-rectal cancer screening, the proportion of
      those with the notification was lower in females than in males, and in those aged
      less than 50 than in those aged 50 or older. There were no differences in the
      proportion between those screened at the work site and those at the occupational
      health service center, and between those positive in the fecal occult blood test
      and those negative in the test but positive in the health interview. These
      results indicated, assuming that the probability of the physicians' notification
      was unrelated to the type of examination, a smaller proportion of the examinees
      positive in the colo-rectal cancer screening consulted a physician for the
      intensive examination later than those positive in the stomach cancer screening.
      It is therefore necessary to make colo-rectal cancer screening effective to
      establish a collaborating system which effectively facilitates the medical
      behavior of the screening positives.

PMID- 9591331
TI  - [Effect of dichloromethane on methylmercury-induced cytotoxicity of rat C6 glioma
      cells].

PMID- 9591332
TI  - [Determination of free silica by visible absorption spectrophotometry].

PMID- 9591334
TI  - Maturation of dendritic cells induced by cytokines and haptens.
AB  - Recently, elucidation has progressed on a crucial role played by dendritic cells
      (DCs) in the induction of primary antigen-specific immune reactions. Although
      mature DCs exhibit potent antigen presenting function, DCs are scattered in
      nonlymphoid organs throughout the body as immature cells that have only minimum
      antigen presenting function. When they are stimulated to maturate, they increase
      their expression of class II major histocompatibility (MHC) antigen and several
      co-stimulatory molecules, resulting in the augmentation of antigen presenting
      function. Furthermore, these maturated DCs move to the T-dependent areas of
      secondary lymphoid organs to sensitize naive T cells for these antigens.
      Therefore, it is important to understand the mechanism to induce the maturation
      of DCs. Recent progress in the study of DC biology depicts various factors, such
      as cytokines, bacterial products and haptens, which are responsible for DC
      maturation. In this paper, the mechanism of DC maturation induced by cytokines
      and chemicals is described.

PMID- 9591333
TI  - [The relationship between body mass index and coronary risk factors].
AB  - We investigated the relationship between the body mass index and the prevalence
      of coronary risk factors, hypertension, hyperlipidemia, glucose intolerance and
      hyperuricemia, in middle-aged male workers. We found a positive correlation
      between the body mass index and the prevalence rate of these coronary risk
      factors. Mean values for serum total cholesterol, triglyceride, LDL-cholesterol
      and HbA1c increased with the increase in the body mass index, but decreased in
      HDL-cholesterol.

PMID- 9591335
TI  - Establishment and characterization of a murine cell-line derived from malignant
      fibrous histiocytoma of A/Jackson mouse.
AB  - A hard mass incidentally found in the right buttock of an elderly male A/J mouse
      was morphologically consistent with malignant fibrous histiocytoma; storiform
      pleomorphic subtype. Diced pieces or suspensions of the tumor tissue were readily
      transplantable subcutaneously in the flank of mice of the strain. The tumor
      bearing mice died mostly of rupture of the tumor into the thorax or abdomen
      within 4 weeks. Pulmonary and splenic metastasis were recognized only in a mouse
      which survived more than 10 weeks. A new cell-line was established from the
      original tumor without necessary cloning and was maintained in MEM (minimum
      essential medium) supplemented with 10% FCS for 6 months under 22 passages.
      Frozen stocks were then made, from which the recovery of the cells was
      successful. The cell growth, requiring about 20 hours for doubling of population,
      was a mixture of plump or stellate histiocytic cells and fibroblastic ones, both
      of which contained lipid droplets and retained phagocytic activity. The cell-line
      was designated as murine sarcoma Sendai (MuSS). Morphological versatility of the
      cultured cells suggested the origin of the neoplasm from multipotential,
      primitive mesenchymal cells.

PMID- 9591336
TI  - Total food duplicate study on nutrient intake of working women in Manila, the
      Philippines.
AB  - Intakes of various nutrients by working women in Manila, the Philippines, was
      surveyed by the total food duplicate method, with foci to elucidate relative
      weight of three meals and snack in addition to quantitative evaluation of
      nutrient intakes. In practice, 45 women (average age; 37.2 years) volunteered,
      who were all nonsmokers and nonhabitual drinkers, and mostly married. In
      parallel, hematology, serum biochemistry, anthropometry and clinical examinations
      were conducted. On average, the women took 1787 kcal energy, 57 g protein, and 54
      g lipid daily. Comparison with the Recommended Dietary Allowances (RDA) for
      Filipinos showed that intakes of energy and major nutrients were adequate,
      whereas that of minerals (e.g., 15 mg Fe/day vs. 26 mg Fe/day as RDA) and
      vitamins (e.g., 0.65 mg vitamin B1/day vs. 1 mg/day as RDA) were generally
      insufficient. Prevalence of anemia was however rather low with an average
      hemoglobin concentration of 12.9 g/100 ml blood. Rice was the staple source of
      energy for daily life, and beef rather than fish and shellfish was the leading
      source of protein. Lunch was the richest meal of a day (with the largest intake
      of energy, protein and lipid), and snacks rather than dinner appeared to be next
      substantial.

PMID- 9591337
TI  - A computer-aided 3-D geometry of acute and chronic zonal necrosis: three-D
      tangent counting applied in an attempt to re-examine the structure of the human
      liver.
AB  - In an attempt to examine the feasibility of the acinar concept in the liver of
      humans, the spatial distribution of zonal necrosis and its relation with the
      blood vessels were studied in terms of 3-D tissue microstructure. The material
      was five autopsy livers, two from patients of acute cresol intoxication and three
      with long-standing heart failure. Examined were: 1) whether the surviving areas
      (zones 1, 2) in acute zonal necrosis have surfaces convex toward the necrotic
      zone 3 as illustrated in the acinar schema, and 2) whether the necrosis extends
      as slender "s eeves" so as to reach the portal tracts and create portal-central
      (P-C) bridging, leaving zones 1 and 2 as a spheroid parenchymal clump. These were
      examined on serial histological sections of the livers, which were subjected to 3
      D reconstruction with the aid of a computer system. The geometric properties of
      the interfaces between the surviving and necrotic areas were analyzed by 3-D
      tangent counting technique of DeHoff modified for 3-D application. It was shown
      by reconstruction that necrosis was uniformly distributed around the hepatic
      venules. In acute cases, tangent counting showed that the surfaces of the
      surviving areas were mainly concave toward necrosis. In contrast, in chronic
      cases, the surfaces became mainly convex as a result of parenchymal regeneration.
      At no place, in acute or chronic cases, was necrosis shown to reach the portal
      tracts, and because of this, neither acini nor their agglomerates revealed
      themselves as a separate unit. All these findings contradict what one expects
      would be, so long as based on the assumption of the acinar model.

PMID- 9591338
TI  - Detection of the PGP9.5 and tyrosine hydroxylase mRNAs for minimal residual
      neuroblastoma cells in bone marrow and peripheral blood.
AB  - The "touchdown" polymerase chain reaction (PCR) technique has been applied to
      analyze expression of the neuron-specific protein, PGP9.5, and tyrosine
      hydroxylase (TH) genes for detection of minimal residual neuroblastoma cells in
      bone marrow and peripheral blood. PGP9.5 and TH gene products were not detected
      in any normal samples (n = 72) examined. However, in patients more than 1 year of
      age with stage III and IV neuroblastoma PGP9.5 mRNA was detected in six of seven
      bone marrow samples and in four of eight peripheral blood samples, and TH mRNA in
      four of seven and three of eight, respectively. The detection sensitivity was up
      to 10(-6) to 10(-7) micrograms of total cellular RNA for PGP9.5 and 10(-4)
      micrograms for TH. Among forty bone marrow specimens from nineteen patients with
      neuroblastoma both PGP9.5 and TH mRNAs were detected in six, and only PGP9.5 mRNA
      was detected in ten. Since detection of PGP9.5 and TH gene transcripts by the
      "touchdown" PCR was highly specific and sensitive, it might be most informative
      at present to carry out both PGP9.5 and TH mRNA assays for minimal residual
      neuroblastoma cells in blood and bone marrow.

PMID- 9591339
TI  - Successful treatment of infertility due to anejaculation with in vitro
      fertilization and embryo transfer: a report of two cases.
AB  - We investigated the efficacy of assisted ejaculation in combination with in vitro
      fertilization and embryo transfer (IVF-ET) in two couples with infertility due to
      anejaculation. Case 1 was in an anejaculatory condition associated with a spinal
      cord-injury. We performed intrauterine insemination (IUI) three times using
      motile sperm obtained by intrathecal injection of neostigmine, but no pregnancy
      followed. The couple then entered IVF-ET. The semen volume obtained by assisted
      ejaculation was 4.5 ml. The sperm count was 33 x 10(6)/ml with 33% motility. At
      35 weeks of gestation she delivered three healthy babies by cesarean section.
      Case 2 was in an unexplained retrograde ejaculatory condition. We performed IUI
      eight times before changing to IVF-ET. We then used sperm obtained from urine or
      sperm recovered from the bladder after administration of human tubal fluid, but
      no pregnancy followed. At the fifth IVF-ET attempt, using sperm obtained from
      urine, we succeeded. We prepared the sperm by the Percoll gradient method. The
      sperm count was 36 x 10(6)/ml with 64% motility. At 39 weeks of gestation she
      delivered a healthy baby. Deficient seminal quality contributes to the decreased
      fertility potential in patients with anejaculation. With the use of IVF-ET
      methods, pregnancies can be achieved in these couples.

PMID- 9591340
TI  - Peripheral blood stem cell transplantation for hepatoblastoma with microscopical
      residue: a therapeutic approach for incompletely resected tumor.
AB  - We report a nine-month-old boy with stage III B hepatoblastoma of caudate lobe
      origin. Surgical resection was attempted following six courses of chemotherapy,
      but viable tumor cells remained microscopically at resection margins.
      Subsequently, he received peripheral blood stem cell transplantation (PBSCT),
      whose preparative regimen being consisted of carboplatin, etoposide,
      tetrahydropyranyl adriamycin, and melphalan. Since then, the patient shows no
      relevance of local relapse or distant metastasis without any chemotherapy. PBSCT
      for patients with post-operative residue may improve the outcome of advanced
      hepatoblastoma and worth of a further clinical investigation.

PMID- 9591341
TI  - [The cytological characteristics of the cells of the multilayer squamous
      epithelium of the cervix uteri in relation to the association of the pathological
      processes with the human papilloma virus].
AB  - An analysis of cytological material in benign (160 observations) and dysplastic
      (101 observations) processes, as well as in cervix outset cancer (38
      observations) with the aim of search for koilocytic atypia markers in the cells,
      existing due to HPV infection, has been carried out. High association degree of
      the virus infection with the material under study has been ascertained. It was
      found out that the increase of koilocytosis phenotypic markers expression rate is
      a reliable criterion of cervix uteri pathologic processes progression. The signs
      of permanent koilocytic atypia in women with dysplasia should be considered as
      prognostic marker of malignant transformation of cervix uteri epithelium.

PMID- 9591342
TI  - [The characteristics of the changes in the vascular endothelium--the main target
      of the action of lipopolysaccharide in endotoxic shock].

PMID- 9591343
TI  - [The evaluation of the cytotoxicity of preparations with anticarcinogenic action
      in human cell cultures].
AB  - An approach for determination of cytotoxicity of chemical and biological drugs
      which combine the estimation of quality and quantity of cells after their
      treatment are proposed by the authors. The visual control of cellular
      minicultures permits one: 1) to register specific and pathologic alterations of
      cell morphology, 2) to trace their development in dynamics under the action of
      individual or complex drugs and 3) to choose the optimum time for the experiment
      fixation. The special staining of the treated cells and measurement of the
      optical density of absorbed histological dye permits one to make a conclusion
      about the changing of the cells quantity. A combined method of double estimation
      gives the opportunity to detect the artefacts taking place after staining the
      cells treated by some drugs and extracts of natural origin in high
      concentrations.

PMID- 9591344
TI  - [The cytological characteristics of a radioresistant variant of the L929 line].
AB  - The dose-effect dependence in the dose interval 5-20 Gy the LD50 for L929 cell
      culture has been investigated. It is 11.8 Gy. After successive irradiation with
      12 Gy LD50 of surviving cell has grown to 14 and 16 Gy. The acquisition of
      radioresistance is accompanied with the increase of cell polymorphism, quantity
      of intercellular contacts and multikaryon structure formation.

PMID- 9591345
TI  - [The dynamics of the cytogenetic effects in the peripheral blood lymphocytes of
      those who worked in the cleanup of the aftermath of the accident at Chernobyl
      Atomic Electric Power Station].
AB  - Dynamics of cytogenetic anomalies in liquidators of the Chernobyl accident has
      been studied. Dicentric and ring frequencies appeared to be the most informative
      criteria of radio-induced chromosome aberrations. The rate of cell elimination
      with dicentrics and rings was higher in liquidators exposed to more than 25 cGy
      of radiation that in those exposed to less than 25 cGy of radiation. The rate of
      elimination of chromatid-type aberrations and genomic mutations was very low in
      the group of liquidators exposed to higher dose of radiation.

PMID- 9591346
TI  - [The genetic selection aspects of the "Holsteinization" of dairy cattle breeding
      in Ukraine].
AB  - Results of the use of Holstein-Friesian bulls in milk-production cattle breeding
      in Ukraine have been stated. Genetic consequences of crossbreeding have been
      noted. An analysis of pedigrees of Holstein bull has shown the availability of
      predecessors carriers of genes BLAD, mule-foot, dumps with frequency of their
      recessive forms 34, 19.3, 3.2%, respectively.

PMID- 9591347
TI  - [Interlocus associations and their variability in cattle].
AB  - The results of analysis of interloci associations between two pairs of syntenic
      loci (transferrin and ceruloplasmin, receptor for vitamin D and kappa-casein) and
      two non-syntenic ones (amylase-1 and post-transferrin 2) in two cattle groups of
      Red Steppe breed (infected and uninfected by bovine leukosis virus) and in two
      groups of Black-and-White Holsteins (from relatively "pure" zone and from the 10
      km zone of Chernobyl NPP) were presented. It is found that "linkage
      disequilibrium" between loci is observed independent of their synteny. The data
      obtained allowed the authors to suppose, that the interloci associations are
      rather controlled by different factors of artificial and natural selection than
      by the genetic linkages between genes.

PMID- 9591348
TI  - [A molecular genetic analysis of spinal muscular atrophy (SMA) in families at
      high risk from different regions of Ukraine].
AB  - The results of DNA analysis of deletion in exons 7 and 8 of SMN gene, and exon 5
      of NAIP gene in 24 SMA-families from Ukraine are presented. Deletions of SMN
      exons 7 and 8, or 7 were found in 46 (97.9%) of 47 SMA-chromosomes. A homozygous
      deletion of NAIP exon 5 was demonstrated in 4 (19%) of 21 SMA-families. The
      authors have demonstrated that in 2 SMA patients with homozygous deletion SMN
      exon 7 only, the remaining SMN exon 8 was a part of a chimeric CBCD41/SMN gene.

PMID- 9591350
TI  - Dating aggression among high school students.
AB  - Links were examined among physical aggression toward a dating partner, parental
      aggression, and justification of physical aggression during an argument in a
      sample of 228 (122 male and 106 female) high school students. Forty-four percent
      of females and 16% of males reported engaging in at least one physically
      aggressive behavior toward a dating partner during a disagreement, with the modal
      form of aggression being push, grab or shove for both males and females. The
      probability that a male, but not a female, would aggress was significantly
      predicted by parental aggression and justification of aggression. Among
      aggressive students, the extent of males' aggression was strongly predicted by
      their justification of aggression; the extent of females' aggression was not
      predictable. Implications for prevention and intervention programs are discussed.

PMID- 9591349
TI  - [An approach to genetic monitoring via a genetic registry].
AB  - The analysis of the selective excerpt of the children with the inherited
      disorders has been made on the basis of the Kiev Medical Genetic Center, where
      the regional anonymous syndromological computer register has been organized.
      Register's file during 1993-96 has the information about 883 families that has a
      genetically ill proband. Genetic syndrome has been diagnosed in 78.02% (105
      nosological points). The information taken from the register has allowed for the
      first time to distinguish the inherited pathology from the acquired one, so the
      new mutation from 30.23% out of all registered inherited disease. The necessity
      of the creation of the National Genetic Register in the Ukraine and the new
      conception of the two-stage genetical monitoring of the population has been
      proved.

PMID- 9591351
TI  - Awareness of guilt and shame in intimate violence.
AB  - The purpose of this article is to examine the role of moral feelings--guilt and
      shame--in the emergence and aftermath of intimate violence, and the way in which
      these emotions affect the self and behaviors of those involved. This is a
      phenomenological study using content analysis of in-depth interviews with 20 male
      batterers and their female partners. The findings indicate that the extent of
      authenticity and assumption of responsibility concerning moral feelings will
      determine whether these will or will not lead to intimate violence. Thus it
      becomes possible to trace five alternative paths of the relationship between
      moral feelings and intimate violence. Implications for theorizing and future
      research about the role of moral feelings in intimate violence are suggested.

PMID- 9591352
TI  - Violent responses to strain: an examination of conditioning influences.
AB  - Past research on General Strain Theory (GST) has not widely examined the
      application of the theory for understanding violent responses to strain.
      Additionally, the theory suggests there may be varying effects of strain on
      possible deviant outcomes across individuals differentiated on their dispositions
      toward deviance. In the current analysis, we examine violent responses to strain
      using original data collected from a sample of college-aged youth. Moreover, we
      specifically examine whether the effects of strain and anger on possible violent
      outcomes are invariant across individuals differentiated on their level of
      exposure to deviant peers and moral constraints against deviance. Using
      structural equation modeling, our results suggest that a composite measure of
      strain increases respondents' intentions to engage in assaultive behavior net of
      other predictors. Additionally, the results reveal that anger mediates the impact
      of strain on possible violent responses. Finally, the results of our subgroup
      analyses suggest that the basic form of the GST model is invariant across groups.

PMID- 9591353
TI  - Anger, aggression, and violence in love triangles.
AB  - Motives for anger and aggression in love triangles are discussed and then
      examined using homicide data and survey data from college students. We find that
      love triangles are a more important motive when females commit homicide than when
      males commit homicide. Females usually kill their lover while males usually kill
      their rival. Male attacks on male rivals reflect identity concerns, according to
      the college student data. Anger at both the partner and rival also depends on the
      assignment of blame. The aggrieved party may attack the partner or rival in order
      to gain retribution or deter future episodes.

PMID- 9591354
TI  - Estimating intruder-related firearm retrievals in U.S. households, 1994.
AB  - To estimate the frequency of firearm retrieval because of a known or presumed
      intruder, the authors analyzed data from a 1994 national random digit dialing
      telephone survey (n = 5,238 interviews). Three mutually exclusive definitions of
      firearm retrieval were constructed: (1) retrieved a firearm because there might
      be an intruder, (2) retrieved a firearm and saw an intruder, and (3) retrieved a
      firearm, saw an intruder, and believed the intruder was frightened away by the
      gun. Of 1,678 (34%) households with firearms, 105 (6%) retrieved a firearm in the
      previous 12 months because of an intruder. National projections based on these
      self-reports reveal an estimated 1,896,842 (95% CI [confidence interval] =
      1,480,647-2,313,035) incidents in which a firearm was retrieved, but no intruder
      was seen; 503,481 (95% CI = 305,093-701,870) incidents occurred in which an
      intruder was seen, and 497,646 (95% CI = 266,060-729,231) incidents occurred in
      which the intruder was seen and reportedly scared away by the firearm. Estimates
      of the protective use of firearms are sensitive to the definitions used.
      Researchers should carefully consider both how these events are defined and the
      study methods used.

PMID- 9591355
TI  - Patterns of reassault in batterer programs.
AB  - A comparative multisite evaluation was conducted of four "well-established"
      batterer programs in geographically distributed cities to assess the pattern of
      reassault. Eight hundred and forty batterers were recruited and tested at program
      intake from each site (210 per site). The batterers and their partners were
      interviewed by phone every 3 months for 15 months after intake with a response
      rate for the female partners of nearly 70% for the full follow-up. According to
      initial victims, 31% of the men reassaulted during the follow-up. The reassault
      rate varies only slightly when adjusting for new partners (32%) or no partner
      contact (32%), but substantially more when adjusting for reports from the
      batterers (36%) and batterers plus arrest record (39%). Rates of verbal abuse
      (70%) and threats (43%) are much higher, but 73% of the women report feeling
      "very safe." Nearly half of the men who reassaulted did so within 3 months after
      program intake. "Voluntary" participants were significantly more likely to
      reassault (44% vs. 29%), as were program dropouts (40% vs. 28%). The "well
      established" batterer programs appear to contribute to a short-term cessation of
      assault in the majority of batterers. However, a small portion of the men are
      unaffected by or unresponsive to the intervention.

PMID- 9591356
TI  - On the kinetics of peptide binding to MHC proteins.
AB  - An experimental study of kinetics of peptide binding to MHC proteins [S. Witt, H.
      McConnell, Acc. Chem. Res. 26 (1993) 442 (and references therein)] showed an
      unusual phenomenon of the so-called 'negative' t1/2 plots (where t1/2 is half
      time of reaching equilibrium concentration of peptide-protein complexes), which
      is the shorter t1/2 at lower added peptide concentrations. The bell-shaped curve
      for t1/2 as a function of peptide concentration is a seemingly peculiar effect,
      because in general, binding reactions go faster with an increase of reagent
      concentrations. It is shown that the suggested explanation of this phenomenon [S.
      Witt, H. McConnell, Acc. Chem. Res. 26 (1993) 442 (and references therein)] is
      misleading (and the numerical simulation used to support this explanation is
      inconsistent with the experimental data), so that the existence of 'negative'
      t1/2 is in no way to be considered as an experimental indication of the two-step
      reaction of peptide binding to protein. This article gives a consistent
      explanation of the bell-shaped t1/2 plots for peptide-protein association and
      obtains the criteria for its existence, based exclusively on the formal chemical
      kinetics analysis of the accepted peptide-protein binding model and briefly
      discusses the experimental data, which really confirm the existence of the two
      step mechanism of binding. The analysis of the maximum location of the half-time
      curves indicates a controversy between the prediction of the two-step binding
      model and the experimental data [S. Witt, H. McConnell, Acc. Chem. Res. 26 (1993)
      442 (and references therein)]: either more complicated mechanism is involved in
      peptide-MHC binding or experimental data [S. Witt, H. McConnell, Acc. Chem. Res.
      26 (1993) 442 (and references therein)] are not quite accurate.

PMID- 9591357
TI  - Effect of charge interactions on the carboxylate vibrational stretching frequency
      in c-type cytochromes investigated by continuum electrostatic calculations and
      FTIR spectroscopy.
AB  - The FTIR spectra of the asymmetric carboxylate absorption region of three c-type
      cytochromes--namely horse heart, yeast and bonito cytochromes c--as well as
      continuum electrostatic calculations performed on their respective protein
      matrices, show that these combined methods can target specific protein regions
      and yield pertinent protein charge information that correlates with the observed
      spectral data. Deconvolution of the IR carboxylate stretch frequency region (1525
      1675 cm-1) in the three cytochromes yield different v(oco)a distributions. In the
      case of the bonito cytochrome c carboxylates, two v(oco)a populations are clearly
      distinguishable in the deconvoluted spectra--which is not the case for the more
      complex v(oco)a deconvolutions of the other two cytochromes. The frequency
      distributions of the calculated potentials are consistent with the experimental
      observations and we conclude that the IR carboxylate absorption in proteins can
      be modified by the electrostatic environment.

PMID- 9591358
TI  - A sedimentation equilibrium study of platypus insulin: the HB10D mutant does not
      associate beyond dimer.
AB  - An extensive study of the self-association patterns of zinc-free synthetic native
      and mutant (HB10D) platypus insulin in solution (pH = 7.0; I = 0.1 M; 25 degrees
      C) has been undertaken using the method of sedimentation equilibrium. The data
      was fitted to a mathematical equation describing the indefinite duoisodesmic
      (IDI) model of self-association [A.E. Mark, P.D. Jeffrey, Biol. Chem. Hoppe
      Slayer, 371 (1990) 1165]. From this the relevant association constants, KA and
      KB, describing the polymerising system were calculated. This information allows
      the calculation of the complex distribution of odd and even numbered polymeric
      species within the insulin system in solution. In the studies on the self
      association of the synthetic native and mutant platypus insulin, each was
      compared with bovine insulin as well as with each other. It is concluded that
      there is some reduction in the extent of the self-association of native platypus
      insulin compared to bovine insulin. A reduction, in specifically the dimer-dimer
      interaction, is indicated by the higher KA and lower KB values. HB10D platypus
      insulin shows a dramatic reduction in self-association compared to native
      platypus and to bovine insulin. Analysis of the self-association pattern yielding
      a KB value of effectively zero suggests that the substitution of an aspartic acid
      residue for a histidine at B10 virtually abolishes its dimer-dimer interaction.
      Platypus insulin has essentially the same biological activity as that of porcine
      (submitted for publication) but a somewhat lower self-association, while the
      introduction of one amino acid in a critical region increases the activity
      twofold while abolishing self-association beyond dimer.

PMID- 9591359
TI  - A long-lifetime Ru(II) metal-ligand complex as a membrane probe.
AB  - A luminescent metal-ligand complex, [Ru(bpy)2(dppz)]2+, (where dppz is
      dipyrido[3,2-a:2',3'-c] phenazine), was used as a photoluminescence probe for
      investigating submicrosecond lipid dynamics in a dipalmitoyl-L-alpha
      phosphotidylglycerol (DPPG) model bilayer system. The luminescence of
      [Ru(bpy)2(dppz)]2+ in buffer is completely quenched but becomes luminescent when
      intercalated into DPPG vesicles. The experimental results show that the emission
      intensity of [Ru(bpy)2(dppz)]2+ intercalated into DPPG vesicles increases
      dramatically as temperature is increased towards the lipid phase transition
      temperature. This effect is abolished in bilayers containing a high concentration
      (> 30 mol%) of cholesterol, suggesting this probe is sensitive to the membrane
      composition. Frequency-domain emission intensity decays, measured as a function
      of increasing temperature towards the lipid phase transition temperature (2 to 57
      degrees C), display two major lifetime components. The short lifetime disappears
      at temperatures well above the phase transition temperature. A comparison of
      oxygen quenching with iodide quenching suggests the heterogeneity of probe
      location at temperatures well below the lipid phase transition temperature and
      the homogeneity of probe location at temperature well above the lipid phase
      transition temperature. [Ru(bpy)2(dppz)]2+ displays polarized emission, enabling
      the study of membrane dynamics. The long decay time displayed by this probe
      allows measurement of the overall rotational correlation time of lipid vesicles
      on the microsecond time-scale. Because of the long lifetime, polarized emission,
      and background free nature of the photoluminescence measurements,
      [Ru(bpy)2(dppz)]2+ has numerous applications in the biophysical studies of
      membranes.

PMID- 9591360
TI  - A nanosecond fluorescence study of the simultaneous influx of Ca2+ and Cd2+ into
      liposomes.
AB  - Nanosecond fluorescence decay characteristics of the calcium-binding probe Quin2
      and two of its cation complexes were examined by time-resolved fluorescence
      spectroscopy. Binding of Ca2+ and Cd2+ resulted in fluorescence lifetime
      enhancements as compared to that of free Quin2 ('tau' = 0.9 ns). The Quin2-Ca2+
      complex displays a monoexponential decay of tau = 7.4 ns, while the cadmium
      complex gives an average decay time of ca. 4 ns. Lifetime measurements made on
      heterogeneous cationic solutions demonstrate that decay times for individual
      complexes can be retrieved. Time-resolved measurements were used to monitor the
      kinetics of ionomycin-mediated calcium and cadmium transport across artificial
      membranes. Fluorescence decays, collected on the time-scale of second, were
      sufficient to measure individual ion fluxes or those of mixtures into liposomes.
      The combination of steady-state and time-resolved fluorescence techniques offers
      the unique advantage of simultaneously detecting other cations in the presence of
      calcium.

PMID- 9591362
TI  - Effects of ANG II and III and angiotensin receptor blockers on nasal salt gland
      secretion and arterial blood pressure in conscious Pekin ducks (Anas
      platyrhynchos).
AB  - The vertebrate renin-angiotensin system controls cardiovascular, renal and
      osmoregulatory functions. Angiotensin II (ANG II) is the most potent hormone of
      the RAS but in some vertebrate animals angiotensin III (Val4-ANG III) may be a
      hormone. We studied the effects of some angiotensins and mammalian ANG II
      receptor antagonists on nasal salt gland function and arterial blood pressure in
      conscious white Pekin ducks. Nasal salt gland fluid secretion (NFS) was induced
      by a 10 ml.kg-1 bw i.v. injection of a NaCl solution (1000 mosmol.kg-1 H2O) and
      maintained by a continuous i.v. infusion of the same solution at a rate of 0.97
      ml.min-1. There was a positive linear correlation between nasal fluid [Na+] and
      osmolality, between [Na+] and [K+], and also between the rate of NFS and [Na+]
      and [K+]. [Asp1, Val5]-ANG II (1 nmol.kg-1 i.v.) inhibited NFS but did not change
      ionic concentrations. Val4-ANG III (1 or 5 nmol.kg-1) and ANG I (1-7) (20 nmol.kg
      1) had no effect on NFS. [Sar1, Ile8]-ANG II (SARILE) acted as an ANG II receptor
      agonist and resulted in a prolonged and complete inhibition of NFS. The AT1
      receptor antagonist, losartan (DuP 753) and the AT2 receptor antagonist, PD
      123319 both failed to block the inhibitory effect of [Asp1, Val5]-ANG II on the
      nasal salt glands. [Asp1, Val5]-ANG II (2 nmol.kg-1 i.v.) increased mean arterial
      blood pressure (MABP), whereas the same dose of [Asn1, Val5]-ANG II (teleost) had
      only 30% of the pressor potency of the avian ANG II. Neither 1 nor 5 nmol.kg-1 of
      Val4-ANG III i.v. nor 20 nmol.kg-1 of ANG I (1-7) had any measurable effect on
      MABP. SARILE blocked completely the pressor response to [Asp1, Val5]-ANG II but
      the AT1 antagonists losartan and CGP 48933 and the AT2 antagonist PD 123319 all
      failed to block the pressor response to [Asp1, Val5]-ANG II. These results have
      substantiated an important role of the nasal salt gland in potassium regulation
      and highlighted a pharmacological dimorphism of saralasin, namely agonist and
      antagonist to angiotensin II-mediated inhibition of nasal salt gland function and
      pressor response, respectively. Using specific nonpeptidergic angiotensin II
      receptor antagonists, we have confirmed the distinct pharmacology of the avian
      angiotensin II receptors in a nongallinaceous species and the absence of
      significant angiotensin I (1-7) and angiotensin II effects on the cardiovascular
      system and nasal salt gland.

PMID- 9591361
TI  - The rate of free radical production as a determinant of the rate of aging:
      evidence from the comparative approach.
AB  - The relationship of oxidative stress with maximum life span (MLSP) in different
      vertebrate species is reviewed. In all animal groups the endogenous levels of
      enzymatic and non-enzymatic antioxidants in tissues negatively correlate with
      MLSP and the most longevous animals studied in each group, pigeon or man, show
      the minimum levels of antioxidants. A possible evolutionary reason for this is
      that longevous animals produce oxygen radicals at a low rate. This has been
      analysed at the place where more than 90% of oxygen is consumed in the cell, the
      mitochondria. All available work agrees that, across species, the longer the life
      span, the lower the rate of mitochondrial oxygen radical production. This is true
      even in animal groups that do not conform to the rate of living theory of aging,
      such as birds. Birds have low rates of mitochondrial oxygen radical production,
      frequently due to a low free radical leak in their respiratory chain. Possibly
      the low rate of mitochondrial oxygen radical production of longevous species can
      decrease oxidative damage at targets important for aging (like mitochondrial DNA)
      that are situated near the places of free radical generation. A low rate of free
      radical production can contribute to a low aging rate both in animals that
      conform to the rate of living (metabolic) theory of aging and in animals with
      exceptional longevities, like birds and primates. Available research indicates
      there are at least two main characteristics of longevous species: a high rate of
      DNA repair together with a low rate of free radical production near DNA.
      Simultaneous consideration of these two characteristics can explain part of the
      quantitative differences in longevity between animal species.

PMID- 9591363
TI  - Molecular characterization and sequencing of antifreeze proteins from larvae of
      the beetle Dendroides canadensis.
AB  - The deduced amino acid sequences of antifreeze proteins (AFPs) from larvae of the
      beetle Dendroides canadensis were determined from both complementary DNAs (cDNAs)
      and from peptide sequencing. These consisted of proteins with a 25-residue signal
      peptide and mature proteins 83 (Dendroides antifreeze protein; DAFP-1) or 84
      (DAFP-2) amino acids in length which differed at only two positions. Peptide
      sequencing yielded sequences which overlapped exactly with those of the deduced
      cDNA sequences of DAFP-1 and DAFP-2, while the partial sequence of another AFP
      (DAFP-3) matched 21 of 28 residues. Seven 12- or 13-mer repeating units are
      present in these antifreeze proteins with a consensus sequence consisting of: Cys
      Thr-X3-Ser-X5-X6-Cys-X8-X9-Ala-X11-Thr-X1 3, where X3 and X11 tend toward charged
      residues, X5 tends toward threonine or serine, X6 toward asparagine or aspartate,
      X9 toward asparagine or lysine, and X13 toward alanine in the 13-mers. The most
      interesting feature of these proteins is that throughout the length of the mature
      antifreeze proteins every sixth residue is a cysteine. These sequences are not
      similar to any of the known fish AFPs, but they are similar to AFPs from the
      beetle Tenebrio molitor.

PMID- 9591364
TI  - Daily torpor and energetics in a tropical mammal, the northern blossom-bat
      Macroglossus minimus (Megachiroptera).
AB  - Little is known about torpor in the tropics or torpor in megachiropteran species.
      We investigated thermoregulation, energetics and patterns of torpor in the
      northern blossom-bat Macroglossus minimus (16 g) to test whether physiological
      variables may explain why its range is limited to tropical regions. Normothermic
      bats showed a large variation in body temperature (Tb) (33 to 37 degrees C) over
      a wide range of ambient temperatures (Tas) and a relatively low basal metabolic
      rate (1.29 ml O2 g-1 h-1). Bats entered torpor frequently in the laboratory at
      Tas between 14 and 25 degrees C. Entry into torpor always occurred when lights
      were switched on in the morning, independent of Ta. MRs during torpor were
      reduced to about 20-40% of normothermic bats and Tbs were regulated at a minimum
      of 23.1 +/- 1.4 degrees C. The duration of torpor bouts increased with decreasing
      Ta in non-thermoregulating bats, but generally terminated after 8 h in
      thermoregulating torpid bats. Both the mean minimum Tb and MR of torpid M.
      minimus were higher than that predicted for a 16-g daily heterotherm and the Tb
      was also about 5 degrees C higher than that of the common blossom-bat
      Syconycteris australis, which has a more subtropical distribution. These
      observations suggest that variables associated with torpor are affected by Ta and
      that the restriction to tropical areas in M. minimus to some extent may be due to
      their ability to enter only very shallow daily torpor.

PMID- 9591365
TI  - Notifiable diseases annual summary. 1995.

PMID- 9591366
TI  - [39th Congress of the German Society for Pneumology, Leipzig, 11-14 March 1998.
      Abstracts].

PMID- 9591367
TI  - [XXXII Congress of the Brazilian Society of Tropical Medicine. Goias, 3-7 March
      1996. Abstracts].

PMID- 9591368
TI  - Morphological study of the forestomach of the Japanese serow (Capricornis
      crispus).
AB  - Details of the morphology of the forestomach of the Japanese serow (Capricornis
      crispus) were examined macroscopically, and by light and scanning electron
      microscopy. The rumen was sac-like in shape, and the right accessory longitudinal
      groove was not visible externally. The reticulum was relatively small, while the
      omasum was oval and large. Inside the rumen, even in the dorsal sac, the ruminal
      papillae were densely distributed, although absent on the pillars. The
      caudodorsal coronary pillar was indistinct. In the ruminoreticular fold, ruminal
      papillae were observed even on the reticulum side. In the reticulum, the primary
      reticular fold was apparent and the ill-defined secondary folds were also
      detected in some reticular cells. In the omasum, the omasal laminae of four sizes
      were recognized. The fourth order of laminae was occasionally absent.
      Histological sections of ruminal papillae revealed that softly keratinized
      epithelium covered the entire ruminal mucosa. In the reticulum, soft keratinized
      epithelium was observed throughout, with the exception of the tips of reticular
      papillae on which the epithelium showed evidence of hard keratinization. The
      epithelium of the omasal laminae was moderately keratinized. On the floor of the
      reticular groove, interlaminar area and in the omasal groove, the accumulations
      of numerous eosinophilic cells were observed in the superficial region. Under the
      scanning electron microscope, shallow transverse grooves were seen on the surface
      of the ruminal papillae. In general, the surface structure seemed to be similar
      to that of sheep rather than cattle. Cellular formations of the collagen fibrils
      were observed at the subepithelial region. In conclusion, examination of the
      forestomach allows classification of the Japanese serows as requiring an
      intermediate type of feeding habit and being between concentrate selectors and
      grass-roughage eaters from a morphological view.

PMID- 9591369
TI  - Omasal anatomy in New Zealand red and fallow deer: an exploratory multivariate
      analysis.
AB  - We measured the weight and volume of omasae, and the number, weight and area of
      omasal laminae from wild fallow (Cervus dama), and wild and farmed red deer
      (Cervus elaphus) whose diet, as indicated by rumen content, was known. A
      multivariate analysis yielded two principal components, interpreted as indices of
      overall omasal size and laminar leafiness. The second component showed
      significantly greater variance in wild red deer than in farmed red or wild fallow
      deer. Deer feeding on a mixed diet of browse and grasses may have greater
      variability of omasal from than those feeding on grass alone. A relationship is
      derived by which the laminar area can be estimated from counts of laminae in
      different size classes.

PMID- 9591370
TI  - Histology and ultrastructure of the gut of the tilapia (Tilapia spp.), a hybrid
      teleost.
AB  - The morphology of the intestine has been studied in a species of warm water fish,
      Tilapia spp., a hybrid teleost of notable economic importance. Light and electron
      microscope results show that the intestine is a relatively undifferentiated
      muscular tube lined with a simple columnar epithelium interspersed with goblet
      cells. The proximal region has a greater surface area, manifested by elongated
      mucosal ridges. The enterocytes are covered apically with uniform microvilli and
      exhibit the typical ultrastructural features of pinocytosis, namely extensive
      invaginations of the luminal plasma membrane and massive accumulation of vesicles
      in the apical cytoplasm. The distal intestine mucosa is thinner and less
      elaborately folded and consists of columnar cells with shorter and sparser
      microvilli. Their supranuclear cytoplasm contains abundant clear vacuoles.
      Numerous endocrine cells can also be seen. Regional cellular ultrastructural
      features are correlated with digestive functions.

PMID- 9591371
TI  - The glandular chambers of the placenta of the bitch in the second third of
      pregnancy (day 30-44): an ultrastructural, ultrahistochemical and
      lectinhistochemical investigation.
AB  - The present study represents the first comprehensive investigation of the
      glandular chambers of the placenta of the bitch. We examined the glandular
      chambers by SEM, TEM, ultrahistochemical and lectinhistochemical methods. The
      glandular epithelium is a high columnar epithelium with club-shaped apical
      protrusions bearing short microvilli. The epithelium forms extensive folds which
      fill up most of the lumen of the glandular chambers. Proceeding to the placental
      labyrinth, the glandular chambers are covered by the tips of the chorionic tufts.
      The trophoblast and the glandular epithelium are separated by a thick layer of
      secretions. The ultrastructure cytology of the columnar epithelium is
      characterized by several Golgi complexes and abundant apical-located mucus
      vesicles with a positive dialysed iron reaction. Lectin histochemistry reveals in
      general a strong reaction of these mucus vesicles with all lectins used. The
      mucus in the lumen of the glandular chamber reacts strongly with WGA, NeuWGA, LPA
      and ConA. The trophoblastic villi projecting into the lumen of the glandular
      chambers are covered by a pseudostratified epithelium consisting of a flat basal
      layer and a superficial columnar one. Its cytoplasm is filled with large fusing
      vacuoles containing longish screw-shaped structures. No morphological equivalent
      of absorption is found. According to the ultrastructure of the trophoblast, the
      significance of the mucus in the glandular chambers in stopping the invasive
      growth of the trophoblast is discussed.

PMID- 9591372
TI  - Morphometrical features of the corneal epithelium in mammals.
AB  - The study has been conducted on 40 species of mammals included in different
      taxonomic orders: 10 carnivores (felines and canides), 13 primates and 17
      herbivores (artiodactyles, perisodactyles and proboscideans). Domestic,
      experimental and wild animals have been included in the sample. The purpose of
      the study is to offer new data regarding morphometric aspects of the epithelium
      of the cornea of mammals. We also aim to establish the relationships and
      differences between the different epithelia studied and to determine the
      morphometric characteristics which best define the epithelium of the different
      species under study. The results obtained have demonstrated the existence of
      correlations between thicknesses, number of cellular layers and number of the
      epithelial cells in the different groups. It has also been established that the
      variants in thickness and number of layers define and characterize the epithelia.
      Finally, the study reveals that morphometric characteristics of the epithelium of
      primates and carnivores have more similarities than those of herbivores.

PMID- 9591373
TI  - Expression of renin in the rat liver.
AB  - Renin is well-known to be a trigger enzyme in the renin-angiotensin system (RAS).
      In contrast to the classical RAS, the local RAS has recently been noted in
      several tissues. The local RAS has a function independent from that of the
      classical RAS, although its physiological principles are not well known. In the
      present study, we immunohistochemically demonstrated that hepatocytes in the rat
      express renin. No renin-immunoreactive cells were detected in rat liver at 0 min
      after death. At 15 min after death, a small number of renin-positive cells was
      demonstrated in the lamina hepatica, and they increased with time to the end of
      observation. Immunoreactivity for renin was scarce throughout the cytoplasm,
      sometimes condensed to below the cell membrane and around the intracellular
      granules. Histoplanimetrically, the values from 15 min to 120 min after death
      were significantly different from that at 0 min after death.
      Hybridohistochemistry revealed no hybrid signals throughout the liver at either 0
      min or 30 min, although renin-immunoreactivity was clearly demonstrated in
      adjacent sections of liver at 30 min after death. In RT-PCR, the radioactivities
      in kidney and liver at 0 min after death were not different from those at 30 min
      after death, respectively. These results suggest the existence of hepatic renin
      in the rat.

PMID- 9591374
TI  - [Anatomic and radiographic examination of the shoulder joint of the cheetah
      (Acinonyx jubatus)].
AB  - Anatomical structures of shoulder joints of five adult cheetahs were examined by
      dissection, corrosion casts and radiography. The bones, capsules and auxiliary
      synovial devices were described, as well as ligaments and adjacent muscles. The
      cheetah shoulder has many similarities with the shoulder joint of the domestic
      cat, but also considerable differences. Proper osteological features were the
      large supraglenoid tubercle, the caudally directed coracoid process and the
      extension of the articular surface of the scapula to the lateral area of the
      supraglenoid tubercle. On the proximal end of the humerus the width of the head
      of humerus, the facet of infraspinatus muscle as a shallow cavity with the
      insertion of the infraspinatus muscle around it and two raised roughnesses on the
      proximal end of the tricipital line for the insertions of the lateral
      glenohumeral ligament and the teres minor muscle were noticeable. The insertion
      of the joint capsule was mainly on the glenoid labrum, only in part of the
      articular surface on the lateral area of the supraglenoid tubercle laterally on
      the scapula. The joint capsule formed a supra- and infraspinatus recess
      laterally, an intertubercular tendon sheet for the biceps brachii muscle
      cranially, and a bipartited subscapular recess medially. An extracapsular
      transverse ligament passing the intertubercular groove, a laterally capsular
      strengthening--called lateral glenohumeral ligament--and an intracapsular medial
      glenohumeral ligament could be found. The latter one was joined to the capsule by
      a mesoligament, dividing the subscapular recess into two pouches.

PMID- 9591375
TI  - Fine structural and histochemical study of equine Paneth cells.
AB  - Ultrastructure, lysozyme and glycoconjugate activity in duodenal Paneth cells
      were observed concurrently in the horse. Paneth cells were seen to uniformly line
      the base of the equine intestinal glands. The round secretory granules have
      centrally located electron densities with peripherally located electron lucent
      halos. Histochemically, the peripheral halo layer was positively stained for
      carbohydrates by the periodic acid-thiocarbohydrazide-silver protein-physical
      development (PA-TCH-SP-PD) method and the entire granules reacted positively to
      the WGA. The central core area reacted with anti-lysozyme. We identified a young
      (Type I) and an old (Type II) cell population in the same crypt, but we suggest
      that the observed populations are variations of the same cell type with the
      varied appearance due to aging of the secretory granules.

PMID- 9591376
TI  - Fetal ependyma in sheep and goat. A scanning electron microscopy study.
AB  - Morphology of the surface of apical membranes of ependymal cells has been studied
      in the whole ventricular system of the brain in goat and sheep fetuses using a
      scanning electron microscope. The surface structure of the ependymal lining
      surface in fetuses of small ruminants is very similar to that in adult animals.
      Supraependymal cells were found only in the lower part of the third cerebral
      ventricle in goat fetuses, but not in sheep fetuses. In small ruminants the
      ependymal surface is already regionally differentiated within the end of the
      first half of prenatal development. Fetal ependyma of goats and sheep, unlike the
      adult ependyma, is characterized by a high secretory activity, which is
      independent of sex or age of fetuses.

PMID- 9591377
TI  - Histological and immunohistochemical study of the cat epididymis.
AB  - A histological and immunohistochemical study of the epididymis of 21 cats which
      ranged from 7 to 8 months to 2 years of age was made. Five different cell types
      were observed in the feline epididymis: principal and basal cells, which were the
      most numerous, apical and narrow, PAS positive cells, which were scarce, and
      migratory cells, consisting of lymphocytes and macrophages. Four morphologically
      distinct areas of the cat epididymis were identified. Region I displayed a
      stellate lumen and the principal cells were tall and presented long and irregular
      stereocilia. In region II, the lumen was oval and the principal cells were
      shorter than in the initial area. Region III displayed characteristics similar to
      those of region I; the principal difference was the presence of short and regular
      stereocilia on the surface of the principal cells. In region IV the lumen was
      very spacious and the epithelium shorter than in the other regions. In regions I,
      II, and III intraepithelial cavities were observed. With regard to the
      immunohistochemical results, the basal cells displayed medium immunoreactivity
      with vimentin. Due to its anti-desmin reactivity, the muscle wall which surrounds
      the epididymis was seen to become progressively thicker as it nears the tail.
      Broad-spectrum anti-cytokeratin serum produced intense immunostaining in the
      basal, apical and narrow, PAS positive cells; the principal cells of region IV
      also displayed a strong immunoreactivity.

PMID- 9591378
TI  - [Application and survival rate of partial fixed dentures with combined retainers
      (adhesion wing, inlay, onlay, overlay, crown)].
AB  - Bridges at least with two types of retainers (adhesive frame-work, inlay, onlay,
      overlay, or crown) might be called fixed partial dentures with combined
      retainers. The aim of the present study was to compare the fixed partial dentures
      with combined retainers made at our clinic between 1986 and 1996. In our study
      the cumulative proportional survival of the combined bridges was found 80%.
      Examining the loss of the combined bridges it seems that in the first year 1% of
      the bridges came off. The rest was lost between 12th and 48th months.

PMID- 9591379
TI  - [OraTest. A new method for differentiating between benign and malignant oral
      tumors].
AB  - This article introduces a new, simple and quick method with which the final
      treatment of the patients with oral risk factors and precancerous lesions can be
      decided. It is a rinsing method with an 0.1% toluidine blue O dye. After a pre-
      and postrinse with acetic acid and toluidin blue dye application the oral mucous
      membrane areas retaining the dye will indicate the possible malignant lesions
      even in those areas where just histologically detectable dysplasia is present. On
      the basis of the literature and on our practice we can advice to use OraTest to
      examine patients in the risk factor group, the patients with suspected disease
      and patients with speckled, exulcerant and erythroleukoplakia.

PMID- 9591380
TI  - [Clinical aspects of pre-prosthetic orthodontic treatment in adults].

PMID- 9591381
TI  - [Assessment of selected hormonal parameters in patients with mastopathy in
      postmenopausal period].
AB  - There have been assessed selected hormonal parameters in patients with mastopathy
      in postmenopausal period. The hormonal evaluation showed significantly higher
      mean concentration of prolactin in blood serum of patients with mastopathy than
      in the blood serum of healthy women. There was not functional hyperprolactinaemia
      in the patients in postmenopausal period. In the examined patients in
      postmenopausal age, there was revealed significantly higher mean concentration of
      oestradiol in blood serum, in comparison with the healthy women. There was also
      found significantly lower mean concentration of follicle-stimulating and
      luteotrophic hormones, which is probably due to enhanced inhibition of
      gonadotrophic hormones secretion by prolactin and oestradiol. The results of the
      conducted hormonal examinations suggest that prolactin is an agent, which
      produces mastopatial changes in women. Furthermore, it seems that genesis of
      mastopathy in postmenopausal period may be connected not only with
      disprolactinaemia but also with persistent oestrogenic activity. It should be
      thus admitted that hormonal examinations (with particular consideration given to
      prolactin) are appropriate management in diagnosis and treatment of patients with
      mastopathy.

PMID- 9591382
TI  - [Effects of continuous estradiol-progestogen treatment on hemostasis in
      postmenopausal women].
AB  - A study was undertaken to asses the effects of oral continuous hormone
      replacement therapy on haemostatic balance. Blood samples were drawn from 28
      postmenopausal women (mean age 54.1 +/- 4.1) with severe climacteric complaints.
      All the women were treated for one year with a continuous oestradiol-progestogen
      regimen which was administrated daily and consisting of 2 mg 17 beta-oestradiol
      in combination with norethisteron acetate, 1 mg (Kliogest-Novo-Nordisk). Hormone
      replacement therapy had no effect on fibrinogen and thrombin time. Activated
      partial thromboplastin time as well as prothrombin time was significantly
      decreased (p < 0.05) respectively 1.7 +/- 3.1 s and 0.6 +/- 1.4 s. No women
      developed crural thrombosis during therapy.

PMID- 9591383
TI  - [Vulvar squamous cell hyperplasia and lichen sclerosus et atrophicus: clinical
      picture, morphology and treatment].
AB  - Treatment of the vulvar squamous cell hyperplasia and lichen sclerosus et
      atrophicus by topical using of corticosteroids and 2% testosterone ointment. The
      period of observation was from 6 months to 18 months. All patients showed
      clinical improvement or full regression depending on the period of disease. In
      all cases histopathologic examination was performed.

PMID- 9591384
TI  - [Usefulness of amniotic fluid index determination in monitoring the effectiveness
      of amniotic infusion in pregnancy complicated by oligohydramnios].
AB  - In our research we intended to evaluate the usefulness of AFI measurements in the
      monitoring of the effectiveness of the amnioinfusions in the cases of pregnancy
      complicated by premature rupture of membranes (PROM), or in the selected cases
      idiopathic oligohydramnios, in pregnancies between 26-36 weeks of gestation.

PMID- 9591385
TI  - [Level of stress during pregnancy estimated by mothers and average weight of
      newborns and frequency of low birth weight].
AB  - Low birth weight is still important health problem in many countries. Children's
      low birth weight increases mortality, injures central nervous system, somatic,
      interferes with intellectual and emotional development. Low birth weight is
      frequently occurring in Poland--between 7-9% of live births. There are many risk
      factors, among them behavioural and environmental. In Poland an attention was put
      on chemical and physical environmental factors. Behavioural factors (stress) are
      disregarded. In the present paper it was decided to check the relationship
      between stress during pregnancy (estimated by pregnant), child birth weight and
      frequency of low birth weight. The research was carried out by use of a
      questionnaire using the "case-control study". In the research were involved 450
      mothers of new-born children (the group of cases: untimely, premature delivery or
      child birth weight below 2500 g) and 450 mothers of new-born children (control
      group-physiologically delivered). Mothers were asked about their relations to the
      pregnancy; professional and personal stress during pregnancy was estimated. The
      results were analysed by counting risk ratio coefficient (RR) and correlation
      coefficient. The research showed, that there is no relation between acceptation
      of pregnancy, stress and frequency of low birth weight or the average child birth
      weight. The researches didn't prove unfavourable influence of stress reaction
      caused by professional and personal stressors on intrauterine foetus development.

PMID- 9591387
TI  - [Trabecular carcinoma (Merkel tumor) of the vulva].

PMID- 9591386
TI  - [The presence of staphylococci in the vagina of pregnant women].
AB  - We were investigating the colonisation rate as well as the quantity of
      staphylococci in the vagina of women with physiological and complicated
      pregnancy. We have found high frequency of staphylococci (coagulase-negative
      and/or coagulase-positive). Vaginal carriage rate amount 90%. According to our
      results neither the presence nor the quantity of these microorganisms were
      related to the presence or the number of lactobacilli, among them to the hydrogen
      peroxide producing ones. We have also assumed that neither colonisation nor the
      quantity of staphylococci have any influence on the course of pregnancy.

PMID- 9591388
TI  - [Pregnancy in nullipara after conservative excision of uterine cellular leiomyoma
      and supplementary GnRH analog therapy].
AB  - The conservatively excised 7 cm in diameter uterine myoma in 34 year old
      nullipara was proved cellular one. Successively the patient received 6 doses
      every 4 weeks GnRH analogue (Zoladex a 3.6 mg s.c.). Four months after
      suppression therapy, the woman conceived. She delivered by caesarean section in
      39 week of pregnancy weight 2800 g, Apgar 7 score.

PMID- 9591389
TI  - [Molecular markers in ovarian cancer].
AB  - Within past few years, the investigation of molecular genetic markers has had an
      increasing influence on clinical decisions about initial treatment and follow-up.
      This review presents data concerning the most studied and interesting molecular
      markers in ovarian cancer. p53 tumour suppressor gene, Bcl-2 oncogene, K-ras
      oncogene, c-erb2 proto oncogene, c-myc oncogene are examples of currently used
      molecular genetic markers. Some of these markers might be useful adjuncts for
      monitoring response to therapy, including early detection of tumour reactivation
      to allow curative therapy and rapid detection of treatment failure. The study of
      these markers may also lead to a better understanding of the biological
      characteristics of ovarian cancer. The information derived from studies of these
      markers also represents the most promising avenue towards new treatment
      strategies.

PMID- 9591390
TI  - [Amniocentesis and amniotic infusion: benefits and risks].
AB  - The introduction of the amnioinfusion technic in the treatment of chosen
      complications of pregnancy, requires an easy access to the amniotic cavity.
      Catheterisation of the amniotic cavity requires the skilled technic, and is not
      associated with the rise of the obstetrics complications.

PMID- 9591391
TI  - [Bases of risk management issues in health impairment in occupational medicine].
AB  - Theoretical issues and practical implications of risk methodology as applied to
      occupational health with account for WHO, ILO and ISO concepts are discussed.
      Conceptual models of risk assessment, risk management and risk communication as
      well as hazard effective exposure approach and optimization criteria (min
      exposure and/or risk and optimum cost/benefit relation) are presented. Priority
      and urgency of risk management procedures are substantiated based on publications
      and standards of England, Germany, EC, etc for different grades of hazardness
      with numerical values of occupational morbidity index (N.F. Izmerov et al.,
      1993b) as quantitative measure of occupational risk for workers' health. The
      usefulness of risk methodology for occupational and environmental health with
      regard to more effective prophylaxis is stressed.

PMID- 9591392
TI  - [New method of determination and standardization criterion in dynamic muscular
      loads].
AB  - Laboratory and industrial investigations using physiologic and ergonomic
      approaches covered dynamic muscular efforts and revealed close correlation
      between inertial, kinematic characteristics of muscular movements and pulse rate
      in low, moderate and intensive locomotory activity. The investigations discovered
      a relationship between pulse rate and ergonomic characteristics in dynamic
      muscular efforts. Using the finding, the authors created ergonomic equivalent of
      pulse rate in dynamic muscular efforts, new method and criterion to regulate
      dynamic muscular effort according to its intensity. The investigations
      demonstrate that the new methods are more informative, if compared to the regular
      ones.

PMID- 9591393
TI  - [Physiological and clinical disorders in muscular work depending on factors of
      work process].
AB  - Clinical and physiologic studies covered 26 occupational groups engaged into
      physical work and revealed that physiologic value of muscular work is a function
      of quantitative parameters, intensity and duration of work. Physiologic value of
      the work appeared to correlate with morbidity structure.

PMID- 9591394
TI  - [Occupational osteopathies (review of the literature)].

PMID- 9591395
TI  - [Summarizing experience concerning certification of workplaces based on work
      conditions].
AB  - The article contains theoretic principles derived from the author's practice of
      working environment assessing. The author suggests and justifies definition for
      the assessing procedure, necessitates improvement and updating of current leading
      documents. Important notion is that development of governmental function-
      regulation of work safety--that is new for Russia, but common for developed
      countries, forms a first step--organization of governmental institution. The
      author necessitates scientific, ergonomic and hygienic basis for further
      development of monitoring system for work safety.

PMID- 9591396
TI  - [Structure of occupational morbidity in St. Petersburg].
AB  - Disorders caused by physical overstrain and physical factors prevail in
      occupational morbidity structure in St. Petersburg, covering the shares of 49%
      and 24% respectively. Pulmonary diseases caused by dust are rare (7%). Strong
      evidence is that these data fail to depict actual prevalence of disease caused by
      dust in the city. Some acute and chronic occupational diseases (electric
      ophthalmia, rhinitis, laryngitis, conjunctivitis) are put into official registers
      rarely. The highest number of occupational diseases caused by physical overstrain
      are seen at various machinery enterprises, in building industry and construction
      materials production.

PMID- 9591397
TI  - [Indicators of occupational morbidity in relation to economically active
      population].
AB  - The authors suggest using 10,000 economically active inhabitants instead of
      10,000 working inhabitants for calculation of occupational morbidity parameters,
      as the first term is wider than the second one excessively used now. The
      parameter suggested is more objective, provides a universal approach to
      evaluation of occupational morbidity level and, therefore, enables to compare the
      parameters for various states.

PMID- 9591398
TI  - Advance in the Rh blood group system.
AB  - The Rh blood group antigens are associated with non-glycosylated red blood cell
      membrane proteins encoded by two closely related genes, RHD and RHCE. Both RH
      genes have 10 exons and the open reading frames of their transcripts are composed
      of 1251 nucleotides. The sequence analyses of RHCE transcripts revealed that
      RhC/c and RhE/e are related to six nucleotide substitutions and a single
      substitution, respectively. Molecular analyses have elucidated the genetic
      background of various RhD and RhCE variants including the Rhnull phenotype with
      neither RhD nor RhCE antigen. The Rh polypeptides require some co-molecules for
      their assembly in the plasma membranes. In fact, several unrelated proteins other
      than those of the Rh polypeptides are reduced or absent on Rhnull red blood
      cells. This group includes the Rh50 glycoprotein, LW glycoprotein, glycophorin B,
      Duffy glycoprotein, and CD47 glycoprotein. The mutation of the RH50 gene is
      inducible of the Rhnull phenotypes. Although the Rh50 glycoprotein is a critical
      co-expressing factor, one or more factors seem to be required to express RhD or
      RhC(c)E(e) antigens on the plasma membranes. Additionally, polymerase chain
      reaction-based tests for Rh genotyping were developed and some have been put in
      practice. Much information obtained from the molecular approach to the Rh blood
      group system has shed considerable light on the Rh polypeptides. In the near
      future, the mechanism of expression, the function, and the evolution of Rh
      polypeptides will be clarified further.

PMID- 9591399
TI  - Urinary output changes in racemic ethylamphetamine and optical activity
      discrimination in rat urine by HPLC analysis.
AB  - Characterization of optical activity and simultaneous analysis of racemic
      ethylamphetamine (EAMP) and its metabolites, as well as the urinary excretion of
      the optical isomers, were examined in rats by high-performance liquid
      chromatography (HPLC). Analysis of the optical isomers of EAMP, amphetamine
      (AMP), para-hydroxy-ethylamphetamine (p-OH-EAMP), and para-hydroxy-amphetamine (p
      OH-AMP) was performed within 90 min. The limit of detection was 30 ng for EAMP
      and AMP, and 60 ng for p-OH-EAMP and p-OH-AMP per 20 microliters injection. After
      oral administration of racemic EAMP, rat urine specimens were collected at four
      intervals, 0-4, 4-12, 12-20 and 20-24 h. After administration of 30 mg/kg EAMP,
      not only each isomer of EAMP, i.e. AMP, p-OH-EAMP and p-OH-AMP, but also an
      unidentified substance (UI) were detected. The UI was presumed to be 3-hydroxy-4
      methoxy-N-EAMP or 3-methoxy-4-hydroxy-N-EAMP by gas chromatographic mass
      spectrometry (GC-MS) analysis. The d-isomer of EAMP was generally excreted more
      abundantly than the l-isomer (p < 0.01-0.05). The d-isomer of AMP and p-OH-EAMP
      was excreted in the first 4 h in a somewhat smaller amount than the l-isomer but
      thereafter in a greater amount than the l-isomer. The d-isomer of p-OH-AMP was
      generally excreted in a smaller amount than the l-isomer (p < 0.1-0.05). The
      total percentages of the dose excreted up to 24 h were 2.65% of the dose of EAMP
      administered [d: 2.04% and l: 0.61%], AMP 3.15% [d: 1.68% and l: 1.47%], p-OH
      EAMP 63.06% [d: 32.68% and l: 30.38%], and p-OH-AMP 2.57% [d: 1.05% and l:
      1.52%]. The optical purity ratio (l/d) of EAMP up to 24 h was 0.31, significantly
      lower than that (1.03) of the original racemic EAMP (p < 0.01). The changes in
      the excretion of EAMP and AMP indicated a stereoselective disposition, but those
      of p-OH-EAMP and p-OH-AMP were unremarkable: the d- and the l-isomer of p-OH-EAMP
      and p-OH-AMP did not differ significantly. The entire amount excreted up to 24 h
      was about 71.43% of the dose administered; the d-isomer 37.45% and the l-isomer
      33.98%. The l/d was 0.91, which was clearly less than that of the original
      racemic EAMP (p < 0.01). These results suggested stereoselective disposition of
      EAMP in the rat, and the methods are potentially applicable to identification of
      the optical activity of EAMP and thereby of methamphetamine abusers.

PMID- 9591400
TI  - [Immunohistochemical study on pulmonary neuroendocrine cells containing
      calcitonin gene-related peptide in sudden infant death syndrome].
AB  - To examine whether pulmonary neuroendocrine cells (PNEC) is associated with
      sudden infant death syndrome (SIDS), distribution and function of PNEC were
      investigated in infants from one to twelve months of age, including 19 cases with
      SIDS and 18 control cases without congenital heart disease and premature birth.
      In this study, lung tissue sections were immunostained with antibodies against
      chromogranin A (CGA) and calcitonin gene-related peptide (CGRP). Although the
      positivity of CGA in SIDS cases was not significantly different from that in
      control, the positivity of CGRP in SIDS cases was lower than that in control
      cases among one to four months old (p < 0.05). Our results suggest that
      respiratory and/or circulatory regulation of cases with SIDS is disturbed by
      reduction of CGRP expression, because CGRP is well known to be a vasodilator, a
      neurotransmitter and a promoter for proliferation of epithelium in airways.

PMID- 9591401
TI  - Detection of ABH blood group antigens from minute human hairs using
      polyvinylidene difluoride membrane with elution--ELISA method.
AB  - A sensitive and simple method for ABH blood grouping of human hairs using a
      polyvinylidene difluoride (PVDF) membrane was described. The hairs sensitized
      with monoclonal antibodies were applied onto the membrane and heated at 60
      degrees C on a hot plate. When the membrane was examined with ELISA using a
      peroxidase-conjugated anti-IgM antibody, group-specific streaky stains were
      perceived on the membrane, because the eluates directly bound to the membrane.
      The present method could be available to the detection of minute antigens of
      short hairs.

PMID- 9591402
TI  - Subtyping of D11S488 STR alleles by single-strand conformation polymorphism
      (SSCP) analysis in two cases of disputed parentage.
AB  - In two normal trio cases of disputed parentage, we analyzed four short tandem
      repeat (STR) loci (FGA, TH01, D20S85, and D11S488). In one case, subtyping of
      alleles at the complex D11S488 locus by single-strand conformation polymorphism
      (SSCP) analysis increased the combined probability of paternity. In the other
      case, subtyping increased the number of loci by which the paternity was excluded,
      from two to three. The present study suggests that inclusion of complex STR loci
      in an STR typing program coupled with the use of SSCP analysis is a practical way
      of parentage testing because of a saving of time and work without sacrifice of
      reliability.

PMID- 9591403
TI  - Binswanger's disease. A rare cause of dementia in elderly persons.
AB  - A 80-year-old in-patient with abnormal behaviors was strangulated in a hospital
      bed by another in-patient while he could not escape from the violence because of
      being restrained to the bed with safety belts. Neuropathological examination of
      the victim's brain showed characteristic pathological changes of Binswanger's
      disease (BD), a rare cause of dementia inducing abnormal behaviors. The authors
      methodically documented BD of the victim and at least justified the restraint as
      a preventive measure of his abnormal behaviors. Although the etiology of BD is
      unknown, immunostaining for glial fibrillary acidic protein of the white matter
      lesions showed neither hyperplasia nor hypertrophy of astrocytes. This result
      suggested that astrocytes may play an important role in the pathogenesis of BD.

PMID- 9591404
TI  - [Forensic medicine in Dar-es-Salaam, United Republic of Tanzania].
AB  - The authors had opportunities to visit and see the present state of forensic
      medicine in Dar-es-Salaam, a capital city of United Republic of Tanzania. In this
      city, Department of Histopathology and Morbid Anatomy in Muhimbili University
      College of Health Sciences is in charge of education and practice of forensic
      medicine. All bodies of unusual death, about 3,000 cases per year, are brought to
      the university mortuary and examined by pathologists. An order of forensic
      autopsy from the Tanzanian police is submitted to the department with details of
      the case, i.e. circumstances of death, witnesses, weapons, etc. In each case, a
      pathologist signs out a death certificate and issues an autopsy report which is
      standardized throughout the country. Embalming after autopsy is essential in a
      tropical country. Tanzania in particular, to prevent both putrefaction of the
      body and dispersion of pathogens during its transportation. Preventive measures
      against biohazards from human immunodeficiency virus-infected bodies are
      considered in the autopsy room and laboratory. Although Tanzania is one of the
      developing countries in the world, the forensic medicine in the capital city is
      rendering great services in the promotion of public health.

PMID- 9591405
TI  - [Hepatic blood flow and imaging of the liver].

PMID- 9591406
TI  - [Frequent chemolipiodolization and prostaglandin E1 administration for
      hepatocellular carcinoma with advanced liver cirrhosis].
AB  - "Frequent Chemolipiodolization & Prostaglandin E1 administration Therapy (FCPT)"
      which performed frequent chemolipiodolization to Hepatocellular carcinoma (HCC)
      and Prostaglandin E1 (PGE1) intra-hepatic arterial administration for avoiding
      serious liver damage by using reservoir was carried out for 7HCC cases with
      severe liver cirrhosis. Chemolipiodolization was performed every 4 weeks to 6
      cases. PGE1 was given to all cases with 10 or 20 micrograms/4 hours every week
      after 7 days administration. In 6 cases that carried out Chemolipiodolization,
      FCPT demonstrated complete response in a case and partial response in 3 cases.
      Two other cases showed the progression of HCC in spite of the frequent
      chemolipiodolization. The serum hepaplastin levels were stable or improved in 5
      cases. Improvement of the serum total protein levels was seen in the long
      survival cases. The general malaise of all cases was disappeared after FCPT. In 5
      cases who had ascites before FCPT, the ascites was gradually decreased. We
      concluded that the FCPT was useful to treat HCC with advanced liver cirrhosis,
      and also the intra-hepatic arterial administration of PGE1 might have the
      possibility that is contributing to the liver function improvement of a liver
      cirrhosis.

PMID- 9591407
TI  - [A case of reflux esophagitis after eradication of Helicobacter pylori].

PMID- 9591408
TI  - [A case report of primary malignant lymphoma of the stomach complicated by
      systemic sarcoidosis].

PMID- 9591409
TI  - [A case of adult intussusception due to the inverted Meckel's diverticulum with
      ectopic pancreas which showed characteristic findings of MRI].

PMID- 9591410
TI  - [A case of acute hepatitis (severe type) due to varicella-zoster virus with DIC].

PMID- 9591412
TI  - [A case of early superficial gallbladder carcinoma associated with suspiciously
      anomalous arrangement of the pancreaticobiliary ductal system].

PMID- 9591411
TI  - [A case of hepatectomy for biloma after transcatheter arterial
      chemoembolization].

PMID- 9591413
TI  - [A case of polypoid cholesterosis of the common bile duct].

PMID- 9591414
TI  - [Deep neck infections in the antibiotic era].
AB  - The paper presents 43 patients treated between 1971 and 1995 in the
      Otolaryngology Clinic of the Pomeranian Medical Academy in Szczecin because of
      deep neck space infections. The authors analyse their own clinical material
      paying particular attention to the diagnosis, microbiology, patients prognosis
      and basic therapeutic procedures. Out of the 43 cases, deaths occurred in 3,
      which denotes 7% mortality rate. The reason for failure was discussed. It was
      revealed that needle aspiration and sonography were for valuable to identify
      early abscess formation. The analyses have confirmed that the prognosis of the
      deep neck space infections is influenced by early diagnosis and prompt, extensive
      surgical treatment.

PMID- 9591415
TI  - [Rhinomanometry of nasal patency in children with complete and secondary cleft
      palate].
AB  - The authors evaluated the morphology of nasal cavities and nasal patency using
      active anterior rhinomanometry in 94 children (mean age 10.2 years). Complete
      bilateral primary and secondary cleft palate was confirmed in 28 children
      (29.8%), unilateral in 66 children (70.2%), where complete right-side primary and
      secondary cleft palate was observed in 19 children (28.8%) and complete left side
      primary and secondary cleft palate in 47 children (71.2%). Measurement methods
      were used according to Rhinomanometric Standardization Committee. Significant
      relationship between nasal patency examined using active anterior rhinomanometry
      and complete cleft palate was confirmed. High, symmetric resistance of nasal
      airflow was observed in children with complete bilateral primary and secondary
      cleft palate. Children with complete unilateral primary and secondary cleft
      palate were found to have asymmetric nasal airflow, higher on the cleft side. In
      this group mean nasal airflow resistance was higher on non-cleft side than in
      population without defects, whereas on clefted side it is approximal to
      population without defects. In children with complete bilateral primary and
      secondary cleft palate mean resistances distribution was symmetric but higher
      than in population without defects.

PMID- 9591416
TI  - Otitis externa malignant. A case report and review of literature.
AB  - Otitis externa malignant (OEM) is a virulent infection if it is not diagnosed and
      treated promptly. Its mortality rate was reported to be 53% when there is
      associated facial nerve paralysis. It usually affects elderly diabetic patients,
      who present with deep-seated pain and other features of non-resolving otitis
      externa. It is mostly caused by Pseudomonas (P) aeruginosa and the treatment of
      choice is anti-Pseudomonas antibiotic. A 64-year-old diabetic male patient is
      described who presented with left ear pain and discharge for two months and did
      not respond to ordinary treatment. The patient also noticed a progressive facial
      weakness on the same side. The clinical presentation, investigations, treatment
      and follow-up of the OEM are discussed on the basis of our case and the review of
      the literature. The diagnosis of OEM is based on high index of suspicion and
      confirmed by histopathologic changes and radionuclide studies. Gallium 67 citrate
      scan is a sensitive way to diagnose and follow up the regression of the disease
      in response to the medical treatment. Ciprofloxacin is the treatment of choice;
      however, it has to be in accordance to culture and sensitivity results.

PMID- 9591417
TI  - [The effectiveness of radiotherapy and the prognostic value of Hb level for
      patients with early glottic cancer (T1N0, T2N0)].
AB  - Effectiveness of radiotherapy as a sole treatment modality was analysed in a
      group of 225 patients with glottic cancer in stage T1 (153 patients) or T2 (72
      patients) without metastases in regional neck lymph nodes. All patients were
      irradiated with gamma 60Co or 10 MeV photons 5 times per week conventional
      treatment with the dose of 2.0-2.5 Gy per fraction. The total dose was in the
      range of 60-70 Gy given in overall treatment time of 30-61 days. 3-year local
      control rate was 88% for T1 patients and 54% for T2. In group T1 total dose of 65
      70 Gy correlated with a high, 94-100%, local rate whereas in group T2 for the
      same range of total dose, extension of overall treatment time beyond 45 days
      caused significant decrease in local tumour control of about 3% for each one day
      of treatment protraction. Moreover, the Hb level was found to be a significant
      prognostic factor and its value below 12 g/dl correlated with remarkably lower
      local control of glottic cancer of about 30% comparing with patients with Hb
      level above 12 g/dl.

PMID- 9591418
TI  - [Osteomas of the paranasal sinuses in the Department of Otolaryngology of Karol
      Marcinkowski University of Medical Sciences in Poznan in 1959-1995].
AB  - In years 1959-1995 in the Department of Otolaryngology of University of Medical
      Sciences in Poznan 112 patients were treated for osteoma within paranasal
      sinuses. In our material there was 59 men and 52 women. The age range was 13 to
      79. Quantitative analysis showed most cases of osteoma in frontal sinus, the
      second place was taken by ethmoidal cells and very rarely was osteoma observed in
      maxillary sinus and sphenoid sinus. Operation procedure was performed on all the
      patients.

PMID- 9591420
TI  - [Results of palliative treatment of advanced regional oropharyngeal cancer].
AB  - We present results of palliative radiotherapy in 76 oropharyngeal advanced cancer
      patients. We recommend, according to appreciated results of palliative treatment,
      the two high fractionation dose courses (so called split course) if the first
      application of high fractionation dose had resulted in partial remission.
      Conventional fractionation dose in the second part of split course of
      radiotherapy did not result in better effect in regression, better subjective
      feeling after radiotherapy and longer survival time in our material. Patients
      with poor presentation status (Zubrod 3) should be excluded from palliative
      radiotherapy.

PMID- 9591419
TI  - [Submandibular pathology as an interdisciplinary problem].
AB  - Basing on the own material of 328 patients treated surgically the authors have
      presented the problem of submandibular space pathology. They have pointed out its
      interspecialty in diagnosing and treatment. Among 328 patients the presence of
      inflammatory tumors have been stated in 220 (67.1%) cases, non-specific
      inflammation in 194 (88.2%) patients and specific inflammation in 26 (11.8%)
      patients. Neoplasmatic tumors have occurred in 98 (29.9%) patients, malignant
      tumors in 78 (79.6%) patients and benign ones in 20 (20.4%) patients. Among
      malignant tumors metastatic ones were observed in 41 (52.6%) cases, while primary
      tumors in 37 (47.4%) cases. In 3.0% patients developmental anomaly have occurred.

PMID- 9591421
TI  - [The effect of primary tumor localization on radiotherapy for supraglottic and
      glottic cancer].
AB  - In the group of 544 patients with squamous cell cancer of supraglottic and
      glottic larynx the effect of primary tumour localisation on the response to
      radiotherapy was analysed. There were 156 patients with glottic cancer T1-T3 N0
      N2 and 388 patients with supraglottic cancer with T1-T4 N0-N3. The most common
      site of extralaryngeal involvement was piriform fossa. All patients were treated
      with the use of external megavoltage beam. The total dose was in range 59-80 Gy.
      The 5-year actuarial disease-free survival was 36% for supraglottic cancer and
      63% for glottic cancer. Primary tumour localisation in glottis correlates with
      more favourable prognosis than that in supraglottic. Extension from supraglottis
      to glottis worsened the prognosis more than that in opposite direction. For
      extralaryngeal involvement the most favourable prognosis was the infiltration of
      lingual-epiglottidean fossa and the worst one for the base of tongue involvement.

PMID- 9591422
TI  - [Study of the vestibule in patients with dizziness and vertigo after 60 years of
      age].
AB  - Aging of the vestibular apparatus is shown to consist of processes similar to
      those occurring in other parts of the nervous system. The recognition of these
      findings is a first step in the clinical differentiation of presbyastasis from
      symptoms related to specific disease processes. Authors had reviewed results of
      otoneurological investigations in the material of 8328 patients and realised that
      1034 of them (12.4%) were over-60-year-old. These patients suffered from
      pathology of peripheral as well as central part of vestibular system.

PMID- 9591423
TI  - [Comparison of rhinomanometry results and selected subjective and objective
      symptoms in patients with seasonal allergic rhinitis].
AB  - The aim of this study was to compare rhinomanometric results with patient's
      assessment of nasal patency, frequency of sneezing, nasal secretion, and results
      of anterior rhinoscopy, 34 patients with seasonal allergic rhinitis were
      examined. Correlations of medium degree were found between the rhinomanometric
      results and both the patient's assessment of nasal patency and the results of
      anterior rhinoscopy. No correlations were found between rhinomanometric results
      and either sneezing or nasal secretion. This might suggest that values measured
      by rhinomanometry are not closely enough connected with those measured by other
      methods and thus rhinomanometry can neither replace nor be replaced with any
      other of the analysed methods for assessing upper airway status.

PMID- 9591424
TI  - [The maxillary artery embolization in the management of recurrent epistaxis].
AB  - The management of recurrent epistaxis, especially posterior epistaxis, is
      difficult. Anterior and posterior nasal packing constitutes the initial
      treatment. Ligation of the ethmoid arteries and maxillary artery is the next step
      if the previous methods fails. We have described three cases with recurrent
      epistaxis; all underwent successful diagnostic angiography and therapeutic
      embolization of the maxillary artery. The role of embolization in the management
      of persistent epistaxis has been discussed.

PMID- 9591425
TI  - [Auditory brainstem responses in the diagnosis of retrocochlear hearing loss:
      selected case reports].
AB  - In this study, four cases of patients with retrocochlear hearing loss are
      presented (acoustic neuroma, cerebellopontine angle tumour, the fourth ventricle
      region tumour, inflammatory or vascular lesions in the fourth ventricle region).
      Standard audiometric tests, auditory brainstem response and radiological
      examinations such as CT scan and MRI were performed in all patients. The abnormal
      ABR observed in all cases suggested retrocochlear hearing loss. The presence of
      retrocochlear disorders was confirmed by CT or MRI. The analysis of presented
      cases showed that the abnormal ABR results should be a sufficient basis for
      referring the patient to MRI examination.

PMID- 9591426
TI  - [Selected parameters of immune reactivity in sensorineural hearing loss patients.
      II. CD3+, CD4+ and CD8+ subsets of T lymphocytes].
AB  - Subpopulations CD3+, CD4+ and CD8+ of T lymphocytes in 67 healthy individuals and
      in 36 sensorineural hearing loss (SNHL) patients with unknown etiology were
      determined. The patients were studied in two groups, i.e. 29 patients with
      bilateral and progressive hearing loss and 7 patients with sudden deafness. The
      ratio of CD4+ and CD8+ was also calculated. The results were presented as the
      mean value for percentage and absolute numbers of the cells together with
      statistical analysis. The acquired results of two group patients with SNHL were
      completed before and at the beginning of ubiquitine therapy. The highly
      significant differences (p < 0.001) for CD8+ subset in comparison with the
      results of control group was found. The restitution effect of ubiquitine
      treatment for CD3+ and CD4+ T lymphocytes subpopulation in SNHL patients was
      observed. Additionally in patients with sudden hearing loss the CD8+ subset was
      also normalized. The ratio of CD4+:CD8+ in patients with bilateral and
      progressive hearing loss was lower (1.27 +/- 0.21) that in control group (1.66 +/
      0.25) and significantly different (t = 7.31; p < 0.001). It was shown that the
      distribution of examined CD system markers which depended on CD4+:CD8+ ratio was
      normal only in 27.6% of patients with SNHL. It was a group of 9 patients in whom
      hearing loss appeared after bacterial or virus infections. No changes in the
      CD4+:CD8+ subpopulation ratio at the beginning of ubiquitine therapy was
      observed. The distribution of normal results for T cell subpopulations in
      patients before and during treatment was presented in table III. Our results
      indicate that the observations may have an important diagnostic value. The
      authors suggest that the CD system antigens determination in monitoring the
      clinical status of SNHL patients and also in patients treated with drugs
      influencing the immune system is needed.

PMID- 9591427
TI  - [Surgical treatment of hearing loss in blue sclera syndrome].
AB  - Etiological theories given in literature, patomechanism and otosclerosis
      reminding traits of the blue scleras syndrome are discussed in this paper. The
      operative methods of repairing conductive hypoacusia in familial blue scleras
      syndrome based on own research are described. The audiological results of hearing
      loss surgical treatment in this case are presented.

PMID- 9591428
TI  - [Sarcoma neurogenes of the larynx].
AB  - Malignant nonepithelial neoplasms of the larynx are rare, and tumors of
      mesenchymal origin constitute 4-6% of all malignant neoplasms of the larynx.
      Sarcoma neurogenes vel malignant schwannoma make up 10% of all soft tissue
      sarcomas. In this paper a case of the extremely rare malignant schwannoma of the
      larynx is presented. In world literature we have met four case reports describing
      tumors of this histological morphology and location.

PMID- 9591429
TI  - [A case of rarely observed cause of congenital dyspnea].
AB  - The authors describe a rare case of congenital dyspnoe caused by "pulmonary
      artery sling". They indicate a role of early diagnosis based on additional
      diagnostic investigation as bronchoscopy, bronchography and oesophagoradiography.
      Surgical correction of the vascular ring allows to maintain the child's life and
      gives possibility of normal further development.

PMID- 9591430
TI  - [A case of giant osteoma of the frontal sinuses].
AB  - A case of giant osteoma of frontal sinus passing into anterior fossa of the
      skull, ethmoid and orbit at the right side in a 17-year-old boy was introduced.
      The osteoma has been surgically removed with neurosurgeon cooperation.
      Considering the large damage of bone, reconstruction of the frontal part by
      "Codubix" was done. Post-surgical course without complications and good cosmetic
      effect were obtained.

PMID- 9591431
TI  - [Bilateral acinar cell carcinoma of the parotid gland].
AB  - Authors have described a case of bilateral acinic cell carcinoma of parotid
      gland. The patient has been treated successfully by left superficial
      parotidectomy and right total parotidectomy followed by complementary Co 60
      therapy. During 3 years after surgery the patient revealed no recurrence of the
      disease. Clinical course, histology and pathology have also been presented. The
      authors have pointed out the difficulties in diagnosing ACC because of the
      variety of histological pictures and unclear terminology.

PMID- 9591433
TI  - [Experimental examinations of the influence of vertebral artery ischemia on the
      function of the inner ear in guinea pigs].

PMID- 9591432
TI  - [Mycosis infection (candidiasis) of the lingual thyroid gland].
AB  - The authors present a case of 60-year-old woman who suffered from a mycosis
      (Candidosis) infection of the ectopic lingual thyroid gland. Intensive
      inflammatory process caused enlargement of lingual goiter and dysphagia occurred
      consequently. Right diagnosis was made after scyntygraphic examination (the
      presence of lingual thyroid gland only), as well as histopathological and
      microbiological examinations which revealed the presence of Candida forms.
      Recovery was achieved after 5 weeks of antifungal treatment--Diflucan during a 2
      week initial period, then followed by 3 weeks of local treatment with nystatin.

PMID- 9591434
TI  - [Function of the parotid gland in patients after radiotherapy for cancer].

PMID- 9591435
TI  - [Theophylline--anti-inflammatory drug].
AB  - Since many years the theophylline have been noted for their bronchodilator
      properties. Several studies have indicated an inhibitory action of theophylline
      on the late response following allergen challenge and his effect was demonstrated
      at lower plasma levels then the so called therapeutic range of 10-20
      micrograms/ml. There is now evidence to suggest that theophylline has anti
      inflammatory actions. It has been recently reported that low dose of theophylline
      reduces the number of activated eosinophils found in bronchial biopsies and
      decreases the number of activated CD.4-lymphocytes in the bronchoalveolar lavage
      fluid. It was detected that neutrophils, eosinophils and monocytes exclusively
      contain PDE-IV. In lymphocytes and alveolar macrophages PDE IV and PDE-III are
      present in different amounts and ratios. Functional studies comparing the
      influence of mono-selective (rolipram-PDE-IV; motopizone PDE-III) dual-selective
      (zardaverine) and non-selective (theophylline) on cell activation considered the
      participation of PDE isoenzymes present in the respective cells. In mast cells,
      macrophages, T-lymphocytes and eosinophils PDE-IV appears to be the predominant
      isoenzyme and inhibits cell activation and secretion. PDE-IV is also involved in
      inhibition of mediator release from epithelial cells and neuropeptides from
      sensory nerves.

PMID- 9591436
TI  - [Typical food allergens for pollinosis in selected regions of Poland. Multiagent
      studies].
AB  - The analysis of the incidence of the positive prick test with food allergens
      among patients with pollen allergy was performed. The 270 patients with
      pollinosis from four allergy centres in Poznan, Lodz and Katowice were examined.
      In each centres the different results were obtained. The influence for this had
      the different status socioeconomic of the patients, the regional habits of
      eating, and often eating the new products in our country. However, among
      examination patients the most positive test with food allergens from all centres
      were nuts, celery, rye flour, carrot, strawberry, pork and beans. The succession
      of this food allergens were changed in four examination centres in respect to the
      number of made prick test but the same allergens had been repeated. These results
      premises to establish the list of the allergens that are needed during diagnosis
      the patients with pollinosis.

PMID- 9591437
TI  - [The effect of selective agonist beta-adrenergic receptors on lung ventilation
      function in patients with chronic obstructive pulmonary disease].
AB  - The aim of the research was to show the influence of Salmeterol on the
      ventilatory parameters in patients with chronic obstructive pulmonary disease
      (bronchitis chronica spastica). In all the patients full lung function test was
      made with the MasterLab-Transfer of the firm Jaeger contains spirometry, flow
      volume and airway resistance. The examination have shown that the average values
      off all analysed indices were higher in the particular examinations than in the
      initial one. Estimating these differences with the test "t Student" it has been
      demonstrated that referring to basic indices the differences were statistically
      essential. We can observe from the comparison of the obtained data that the
      growth of the indices took place in the substantial majority of patients.

PMID- 9591438
TI  - [Eosinophil cationic protein in children with allergic diseases of the
      respiratory tract in exacerbation and remission of symptoms].
AB  - The role of eosinophil cationic protein (ECP) in allergic inflammatory reaction
      has been documented in experimental and clinical studies, but a clinical
      usefulness is still discussed. In the study serum level of ECP has been evaluated
      in children with allergic diseases of the respiratory system in exacerbation and
      remission of symptoms for purpose of monitoring of disease course. In 111
      children aged 12.0 +/- 3.3 yrs with atopic bronchial asthma and/ or allergic
      rhinits ECP serum concentrations have been determined in following groups:
      children with grass pollen hypersensitivity (group P, 17 female and 41 male),
      children with hypersensitivity to D. pteronyssinus and D. farinae (group D, 16
      female and 37 male) and controls without allergic hypersensitivity with negative
      prick skin tests (19 children, 11 female and 5 male). All children have been
      qualified to immunotherapy with pollen or mite allergens (Allergovit or Novo
      Helisen, Nexter, Allergopharma) and ECP evaluation was performed before, during
      and after therapy. Serum ECP and IgE levels have been determined with CAP-system
      (Pharmacia) and obtained results related to clinical symptoms. In all analyzed
      children serum total IgE has been significantly increased in relation to
      controls. Serum ECP levels have been increased during clinical exacerbation of
      symptoms in observed children and parallel with clinical score of symptoms,
      especially during pollen season. Authors conclude that a degree of increase of
      serum ECP level is parallel with clinical score of symptoms, especially during
      highest exposition to pollen allergens. Observed changes of serum ECP levels
      during immunotherapy suggest the close relationship with allergic inflammatory
      reaction and indicate clinical usefulness for monitoring of this process.

PMID- 9591439
TI  - [Resistance of Haemophilus sp. to antibiotics].
AB  - The present study was undertaken to determine the in vitro drug resistance of
      Haemophilus influenzae (68 isolates) and H. parainfluenzae (17 isolates). The
      tests susceptibility to Ampicillin, Amoxicilin/Clavulanic Acid, Cefaclor,
      Cefuroxime, Cotrimoxazole, Aztreonam, Ceftriaxone, Tetracycline, Ciprofloxacin,
      Rifampicin and Chloramphenicol were performed with a standard disk-diffusion
      method. The NCCLS methodology and susceptibility interpretative criteria were
      applied as described by the disk manufacturer. Beta-lactamase production was
      detected with nitrocefin impregnated disk (Cefinase, BBL Microbiology System).
      Resistance in nosocomially acquired Haemophilus isolates to several antibiotics
      was observed. Of the Haemophilus isolates 28.2% were Ampicillin in resistant, all
      were susceptible to the combination of Amoxicillin/Clavulanic acid. The
      Ampicillin-resistant strains were beta-lactamase producers. We observed the high
      resistance (70.1%) to Tetracycline and (28.2%) to SXT (Cotrimoxazole). All
      isolates of Haemophilus were susceptible to Ciprofloxacin. The low resistance
      percentages to Rifampin (1.2%), Aztreonam (3.5%) and Chloramphenicol (3.5%) was
      observed.

PMID- 9591440
TI  - [Atenolol in the treatment of patients with airway obstruction].
AB  - Tachycardia in the asthmatics and bronchitis patients is very frequently
      observed. Atenolol-beta 1 selective beta-blockers, have little lipophilicity and
      intrinsic sympathetic activity and relatively long acting. It is known that
      atenolol more then other beta-adrenergics decreases frequency of cardiac rhythm
      even in a doses which have not antiarrhythmic nor hypotensive action. Atenolol
      effect on airways resistance was studied in patients with chronic bronchitis and
      bronchial asthma determining the heart rate, pulse and atrial blood pressure and
      the vital capacity (VC), forced expiratory volume (FEV1%VC), value of maximal
      expiratory flow at 50% of VC(MEF50) thoracic gas volume (TGV) and bronchial
      resistance (Rt). A statistically significant difference in the measurements of
      heart rate and pulse but no rise of the airways resistance after 25-50 mg
      atenolol per day was observed.

PMID- 9591441
TI  - [Fluticasone propionate, corticosteroid for topical treatment].
AB  - The aim of this study was to evaluate the usefulness of fluticasone propionate in
      various dermatoses and to present the data to non-dermatologists. The study was
      performed at the Department of Dermatology, University School of Medicine in
      Poznan. The studied group consisted of 40 cases of various types of eczema,
      psoriasis vulgaris, DLE, photodermatoses and morphea. Fluticasone propionate
      cream or ointment was applied to lesional skin twice daily for 7-19 days. Acute
      eczematous skin lesions significantly improved after the first seven days of
      treatment, whereas in patients with chronic eczema the good therapeutic results
      were observed after 14-19 days. Fluticasone propionate was also effective in the
      treatment of DLE and photodermatoses.

PMID- 9591442
TI  - [Comparison of reproducibility of selected allergologic tests in vitro].
AB  - The aim of our study was the comparative evaluation of allergological tests in
      "in vitro" examinations. We conclude the similar results in both allergological
      tests: Allergodip (Allergopharma) and CAP FEIA (Pharmacia).

PMID- 9591443
TI  - [Recurrent upper respiratory infections in left atrial myxoma].

PMID- 9591445
TI  - [Pneumonia caused by Legionnaire's disease?].

PMID- 9591444
TI  - [Lasting hearing loss in the course of neuro-borreliosis].
AB  - Lyme borreliosis is spirochetal disease that frequently affects the nervous
      system months or years after infection giving rise to a varied clinical picture
      named neuro-borreliosis. We report a case of 47 year old female with progressing
      hearing loss, tinnitus, paraparesis and ataxia. The disease was beginning six
      month earlier by weakness of the lower limbs associated with hearing loss. The
      patient did not remember to be exposed to ticks and did not recall the presence
      of erythema migrans, arthritis or other systemic signs. CSF was with mononuclear
      pleocytosis and protein concentration over 600 mg%. Firstly patient was
      unsuccessfully treated like encephalomeningitis with tbc etiology. Next
      cerebrospinal fluid analysis showed presence of antibodies against Borrelia
      burgdorferi in IgG and IgM class. IgG antibodies in serum were founded.
      Audiometry electric responses from brain stem showed sensorineural hearing loss.
      Therapy with ceftriaxone was successful. Because negative tick bile history and
      many signs from different parts of CNS, relationship of this spirochetal
      infection and severe otolaryngological and neurological disease was firstly
      difficult to recognition.

PMID- 9591446
TI  - [Legionnaires' diseases].

PMID- 9591447
TI  - [Does Legionnaires' disease exist in Poland?].

PMID- 9591448
TI  - [Chronic cor pulmonale--a disease of the right or both ventricle(s) of the
      heart?].
AB  - Some aspects of the development of chronic cor pulmonale have been presented.
      Special attention has been paid to the possibility of simultaneous formation of
      changes in the muscle of both ventricles of the heart and to an increase in the
      number of capillaries in the myocardium in the early stage of this disease.
      Angiogenesis, the role of hypoxia and endothelins in the pathogenesis of these
      changes have been discussed.

PMID- 9591449
TI  - [Early post myocardial infarction syndrome--a trial of assessment based on
      clinical course and immunologic tests].
AB  - The study analysed clinical and immunological course of 22 patients (aged 56.3 +/
      9.5) with fever (38.5 degrees C) and greatly increased erythrocyte sedimentation
      rate (ESR) in the first week after myocardial infarction. The control group
      consisted of 25 patients (aged 50.7 +/- 11.2) without inflammatory and infectious
      diseases. Clinical courses of the disease, chest x-ray, echocardiography,
      leucocytosis and serial CK-MB levels were analysed. The immunological
      investigations involved quantitative estimation of IgG, C3 complement, C4
      complement and the identification of T and B lymphocytes on the basis of the
      rosette tests A, E and EAC. Post myocardial infarction syndrome (PMIS) manifested
      by fever and greatly increased ESR we observed in 64% of examined patients, but
      fully manifested PMIS in 14% with tendency to recurrences. We found the
      differences in immunological examinations compared to the control group.
      Pericardial effusion occurred in 64% of the patients. The treatment with
      corticosteroids brought dramatic relief of the symptoms with objective
      improvement of clinical condition. Patients with high temperature with
      accompanying greatly raised ESR in the first week after MI may demonstrate
      abortive form of the post myocardial infarction syndrome.

PMID- 9591450
TI  - [Selected renal complications during the course of multiple myeloma].
AB  - Multiple myeloma is the most frequent dysproteinemia leading to nephropathy. The
      aim of the study was to analyse this complication in patients treated in
      nephrological departments. The study was performed in 83 patients (45 M, 38 F)
      aged 47-82 years in whom a diagnosis of multiple myeloma was based on clinical
      manifestation (weakness, subfebrile states, bone aches, loss of body weight,
      recurrent infections of urinary and respiratory tracts), increased number of
      plasmocytes in bone-marrow, presence of monoclonal protein in serum and/or urine
      and lesions in bone system. In a significant number of the studied patients the
      disease was revealed while diagnosing proteinuria as well as searching for a
      reason of elevated erythrocyte sedimentation rate or proteinogram abnormalities.
      The obtained results indicate that signs of nephropathy in the course of multiple
      myeloma may be the first visible symptoms of the disease. Proteinuria was
      observed in 79.5% of the studied patients. Bence-Jones protein was found in 41%
      of individuals and features of renal failure in different stages of development
      in 67%. Dialysis therapy was started in 3 patients with acute and 7 patients with
      chronic renal failure.

PMID- 9591451
TI  - [Surgical treatment of secondary hyperparathyroidism in patients treated with
      renal replacement].
AB  - Between January 1990 and July 1997, in 15 maintenance dialyzed patients and in 3
      patients after renal transplantation manifesting hyperparathyroidisms surgical
      treatment was performed. The diagnosis was based both on the estimation of serum
      PTH level, total and ionised calcium, phosphates, alkaline phosphatase and
      imaging procedures: ultrasonography and 99-mTc subtraction scintigraphy.
      Indications to surgical treatment included ailments like generalized prurigo,
      bone and joint pains and muscular weakness with no response to pharmacological
      treatment. The commonly used procedure was subtotal parathyroidectomy (94%), its
      extent, however, was in each case determined during surgery, depending on the
      quantity and size of parathyroid glands found. In all cases the immediate
      intraoperative histopathological examination of the resected tissues was
      performed. In 10 patients resection of the thyroid gland tissues was carried out
      because of goiter (56%), among them in 1 case occult papillar carcinoma was found
      in histopathological examination. In the postoperative period 4 patients (22%)
      manifested transient hypocalcemia with good response to pharmacological
      treatment. Good results of surgical treatment reflected by both ailment relief
      and normalization of serum PTH and phosphates were obtained in 16 patients (89%).
      In 2 patients (11%) the ailments subsided but did not completely disappear.
      Surgical treatment of secondary hyperparathyroidism by subtotal parathyroidectomy
      is efficacious and entails a low risk of complications.

PMID- 9591452
TI  - [Use of the Digene Hybrid Capture System for identification of the human
      papillomavirus (HPV-Human Papillomavirus) in women with cervical dysplasia].
AB  - The study was performed to assess prevalence of HPV-DNA infections using the
      Hybrid Capture System (Vira Papl Vira Typ ). In a group of 228 female patients
      with Papanicolaou smear grade I and II, high oncogenic risk HPV infections were
      found in the 15.78% and low oncogenic risk--in 7.01% of the investigated
      patients. In a group of 324 women with diagnosed CIN, the high oncogenic HPV
      infection were found in 70.4% of them (CIN I/II-60%, CIN III-87.11%), and the low
      oncogenic risk HPV infections in 11.1%.

PMID- 9591453
TI  - [Level of sialic acid in blood serum as a tumor marker].
AB  - In the recent quick development of cancer diagnostic methods, attention of
      researchers is focused onto tumor-derived compounds as possible markers of
      neoplasia. In this article we have reviewed researchers' opinions about sialic
      acid as a tumor marker. According to majority of researchers, blood sialic acid
      may be regarded as a useful marker for a variety of cancers although its
      specificity is not high.

PMID- 9591454
TI  - [New imaging methods in diagnosis of lung cancer].
AB  - The paper reviews new imaging methods allowing more precise diagnosing and
      staging of lung cancer. From among the methods currently used in clinical
      practice computed tomography and nuclear magnetic resonance were reviewed.
      Advantages and limitations of these techniques were presented. As for isotopic
      tests we reviewed single photon emission computed tomography and positron
      emission tomography as well as novel endoscopic methods--lung imaging
      fluorescence bronchoscopy and video assisted thoracoscopy.

PMID- 9591455
TI  - [The role of ionized radiation in prevention of restenosis after coronary
      angioplasty].
AB  - Restenosis occurs to be an Achilles heel of coronary interventions. Three
      overlapping processes: elastic recoil, neointimal proliferation and arterial
      remodelling are responsible for development of arterial renarrowing. The only
      method which proved efficient in reducing the restenosis rate is coronary
      stenting. Stents deployed using high pressure technique diminish restenosis rate
      by about one third. Stents eliminate elastic recoil and arterial remodelling but
      aggravate neointimal proliferation. A concept of radiation therapy was introduced
      to solve the problem of neointimal hyperplasia. Experiments on animal models of
      restenosis proved that both gamma as well as beta irradiation inhibited
      neointimal proliferation after arterial injury. Results of experimental
      investigations concerning both intraarterial irradiation during angioplasty as
      well as radioactive stent implantation are reviewed. Authors discuss also results
      of first clinical trials, the design and preliminary results of some larger
      studies like PARIS, SCRIPPS, GENEVA, BERT, IRIS, WRIST. Further investigational
      directions in intravascular radiation therapy are also presented.

PMID- 9591456
TI  - [The role of cytokines in ocular inflammation].
AB  - In this paper the immunological mechanisms connected with cytokines in the
      intraocular inflammation were discussed. The attention was paid to the possible
      involvement of a cytokine--network in the development of uveitis.

PMID- 9591457
TI  - [Atypical case of bronchial carcinoid].
AB  - This article illustrates problems in diagnosis and treatment of an atypical form
      of bronchial carcinoid. We described the case of a 49-year old man, exposed to
      granite dust and noise for 25 years who had suffered from frequent bronchitis
      inflammations and pneumonias for 5 years prior to the diagnosis. He was admitted
      to our clinic because of supposed occupational nature of hearing deficiency.
      Although a pneumoconiosis was excluded before the admission, we found clinical
      and X-ray features of the right lung emphysema with medium restrictive
      ventilation disturbances. Bronchoscopy was performed because of "bright" right
      lung and ventilation disturbances and it showed presence of the carcinoid.
      Unusual in this case were tiny anamnestical findings (mild dyspnea attacks after
      physical effort or nervousness) plus increasing frequency of reported from the
      childhood bronchitis and pneumonias and uncharacteristic "bright" right lung in X
      ray. Therapeutical difficulties resulted from atypical histological form of the
      tumor, its diameter, polypous-infiltrative character, and inconvenient
      localization. In spite of late diagnosis of carcinoid and significant
      acceleration of respiratory decompensation symptoms after the diagnosis the
      attempt of surgical therapy was appropriate but unsuccessful. After the operation
      the patient was suffering long lasting lowering of arterial pressure (what was
      corrected with catecholamine infusions) probably as a result of serotonin
      secretion. However it was not established because of technical reasons.

PMID- 9591458
TI  - [The case of a 27-year old patient's survival with CREST syndrome].
AB  - The case of CREST-syndrome in a course of scleroderma was described. The authors
      discussed new methods of therapy of this disease as well as emphasized the long
      survival time and noninvasive cure methods.

PMID- 9591459
TI  - [Michael Balint and his conceptions of medical education of physicians for
      effectiveness in working with patients].
AB  - The paper presents conception of the education of students and physicians in the
      Balint's group. The most important is the Balint's idea is to present fundamental
      relations between the physician and the patient. A therapeutic effect is the
      result of the very good understanding, confidence, tolerance, positive emotions
      between physician and patient. The Balint's group changes the physician's
      attitude, the relation to the patient is more intensive, there less fear is more
      intensive, there less fear and frustration. In the Balint's idea very important
      is an intensity and quality of the therapy. In the group with the leader,
      students and physicians learn to understand themselves in the emotional and
      intellectual areas.

PMID- 9591460
TI  - ["He lived for common benefit" (Anniversary of Sebastian Petrycy in the 370th
      year after his death)].

PMID- 9591462
TI  - [Peptides and their biological activities from invertebrates: molluscs and
      annelids].

PMID- 9591461
TI  - [Jageillonian University medical students' relationship to awarding of the
      doctorate degree in all medical sciences in the period between wars].
AB  - The Academic Schools Act of 1920 and the Ordinance of 1924 pertaining to
      doctorates provided that one could earn the degree only having submitted a
      disseration. The Austrian Act which was in force up to that moment had allowed to
      receive the degree without writing a thesis. Protests voiced by medical students
      extended validity of the Act. The Jagiellonian University medicals played an
      important role in delaying the Ordinance coming into force. Protesting against
      the newest regulations they organized public meetings, wrote memorials and filled
      petitions. The Jagiellonian University Faculty of Medicine granted doctorates
      without dissertation up to the end of December 1932. However some doctorates were
      granted even after that term.

PMID- 9591463
TI  - [Molecular biological aspects of Werner's syndrome, a model for premature
      ageing].

PMID- 9591464
TI  - [A family of the intracellular calcium-binding proteins with five EF-hand
      motifs].

PMID- 9591465
TI  - [Membrane-bound aminopeptidases].

PMID- 9591466
TI  - [Mitochondrial uncoupling protein as a thermogenic molecule].

PMID- 9591467
TI  - [Translational inhibitor protein, PSP].

PMID- 9591468
TI  - [Role of protein N-myristoylation in HIV-1 gag protein].

PMID- 9591469
TI  - Effect of cisapride on myoelectrical activity of the gastrointestinal tract in
      the conscious miniature pig.
AB  - In conscious miniature pigs with electrodes implanted in the wall of the antrum
      pylori, duodenum, jejunum, ileum and caecum, the influence of intravenous
      injection of cisapride, 0.5 and 1 mg/kg, on gastrointestinal myoelectrical
      activity, was examined. Cisapride, 1 mg/kg, induced a delayed and sustained
      increase in antral myoelectrical activity. The studied intestinal segments were
      rather insensitive to the stimulating effect of the benzamide, since only the
      jejunum and the caecum revealed an increase in myoelectrical activity with the
      higher dose studied.

PMID- 9591470
TI  - Changes of histamine concentration in chicken oviduct during the egg-laying
      cycle.
AB  - This study was undertaken to determine histamine concentration in chicken
      oviductal parts (infundibulum, magnum, isthmus and shell gland) in relation to
      the egg location within the oviduct and ovulation. The experiment was performed
      on Hisex Brown laying hens with regular sequences of at least four eggs.
      Ovulation occurred within 5-15 min of oviposition of the previous egg in the
      series. Histamine was determined spectrofluorometrically in the following stages
      of the egg-laying cycle: during c2 oviposition; 0.5 h, 6.5 h, 12.5 h and 18.5 h
      after c2 oviposition; and during c3 oviposition. Irrespective of the egg
      formation stage histamine concentration in the examined oviductal parts was
      arranged in the following order: infundibulum > magnum > isthmus > shell gland.
      During the egg-laying cycle histamine concentration significantly changed. During
      oviposition, i.e. just before ovulation of the next egg in the series, histamine
      concentration significantly increased in the infundibulum while 6.5 h after
      oviposition, i.e. about 1.5 h of the egg stay in the shell gland, there was a
      significant increase in histamine concentration both in the infundibulum and the
      shell gland. In the magnum histamine concentration was elevated when the ovum
      entered the segment, i.e. 0.5 h after oviposition. There were no changes in
      histamine concentration in the isthmus. It is suggested that histamine
      participates in the local events taking place in the hen oviduct during the egg
      formation cycle.

PMID- 9591471
TI  - Diagnosis of Aujeszky's disease virus infection in dogs by use of
      immunohistochemistry and in-situ hybridization.
AB  - Aujeszky's disease (AD) was diagnosed in seven dogs by histological examination,
      immunohistochemistry and DNA in-situ hybridization. All dogs which lived on two
      swine farms died spontaneously showing an acute neurological syndrome
      (hypersalivation, vomiting, pruritus, depression and coma). The most significant
      histopathological lesion was a non-suppurative encephalitis located in the brain
      stem, mainly near the floor of the IVth ventricle. Aujeszky's disease virus (ADV)
      antigen and ADV nucleic acid distribution coincided with the histopathological
      lesions. However, little ADV antigen and ADV nucleic acid was found in severely
      damaged areas. A few neurons stained intensely by immunohistochemistry and in
      situ hybridization in non-inflammatory areas. Both immunohistochemistry and in
      situ hybridization techniques are valid techniques to confirm ADV infection in
      paraffin-embedded tissues and will be useful for characterizing the pathogenesis
      of ADV in the central nervous system (CNS) in carnivores.

PMID- 9591472
TI  - High incidence of cardiac arrhythmias in broiler chickens.
AB  - A study was completed to characterize cardiac arrhythmias in broiler chickens.
      The data were collected from 505 (265 males and 240 females) commercial broilers.
      Electrocardiograph (ECG) readings were obtained from all birds between 7 and 9,
      21 and 23, and 42 and 44 days of age. For comparison, ECG recordings were also
      collected from 180 broiler breeders at 3 and 8 weeks of age, and from 100 6-week
      old Brown Leghorn and 100 6-week-old Barred Plymouth Rock chicks. The
      measurements included evaluation of heart rhythm, and incidence of ascites and of
      sudden death syndrome (SDS). Heart arrhythmias in broiler breeders or in the two
      other breeds examined were sporadic. Cardiac arrhythmias in broiler chickens were
      seen as early as 7 days of age. The incidence of arrhythmias increased with age.
      At 42-44 days of age 17% of the broiler population showed disrhythmia. The
      incidence was higher in male broilers (P < 0.012) in comparison to females. The
      most frequently observed disturbances of the rhythm were ventricular arrhythmias
      (VA), the most common being premature ventricular contractions (PVC). In most
      cases PVC occurred as one or two episodes, but in several birds, runs of three or
      more consecutive PVCs occurred. Unifocal PVCs were considerably more frequent
      than multifocal PVCs. Sustained ventricular tachycardia (VT) was least frequent.
      Heart-related mortalities were observed only in broiler chickens. There were 23
      SDS cases (4.55% of the population) and 13 birds developed ascites (2.25% of the
      population). Male broilers had a higher incidence of SDS (P < 0.027) and ascites
      (P = 0.064) compared to females. Males represented 74% of all SDS cases and 77%
      of all ascites cases. Whereas three birds that died of SDS and one bird that
      developed ascites had a history of VA, five birds that developed ascites had a
      history of conduction block. It has been concluded that, compared to other
      chickens, the hearts of broiler chickens are considerably more susceptible to
      arrhythmias. Cardiac arrhythmias are involved in the pathogenesis of SDS and are
      likely in some cases of ascites.

PMID- 9591473
TI  - Evaluation of the analytical performance of an enzyme immunometric assay (EIA)
      designed to measure endogenous thyroid-stimulating hormone (TSH) in canine serum
      samples.
AB  - The analytical performance of a commercially available enzyme immunometric assay
      (EIA) designed to measure endogenous thyroid-stimulating hormone (cTSH)
      concentration in canine serum samples was evaluated. The precision of the assay
      was acceptable with intra- and inter-assay coefficients of variation (CV) of 5
      and 11%, respectively. The assay maintained linearity under dilution and
      recovered added cTSH in a linear and proportional manner. The limit of detection
      (0.03 microgram/L) was well below the values measured in serum from dogs with
      primary hypothyroidism (median value 1.52 micrograms/L). Further, the assay
      clearly distinguished dogs with primary hypothyroidism from clinically healthy
      dogs (P = 0.0004). Based on these findings, it was concluded that the analytical
      performance of the assay was acceptable.

PMID- 9591474
TI  - Clinical, haematological, metabolic and endocrine traits during the first three
      months of life of suckling simmentaler calves held in a cow-calf operation.
AB  - Newborn suckling Simmentaler calves (10 males and 9 females) in a cow-calf
      operation were examined from birth up to the age of 3 months. The average daily
      gain from 47 to 120 kg was 0.86 kg. Except for higher average daily weight gains
      and insulin-like growth factor-I concentrations and lower thyroid hormone levels
      in male than female calves, there were no significant sex differences. Plasma
      glucose, total protein and immunoglobulin G concentrations increased on day 1 of
      life, thrombocyte number and plasma triglyceride concentrations rose during the
      first 7 days, whereas lymphocyte and monocyte percentage and plasma inorganic
      phosphorus, phospholipid, cholesterol and albumin concentrations increased during
      the first 14 or 21 days and then remained elevated. Eosinophil percentage
      increased after 3 weeks and insulin-like growth factor-I concentrations increased
      over the whole growth period. There were transient elevations of plasma glucagon
      concentrations up to day 14, of the activity of alkaline phosphatase transiently
      up to day 7 and of gamma-glutamyltransferase, aspartate aminotransferase and
      lactate dehydrogenase activities on day 1 of life. Plasma iron concentration
      transiently decreased up to day 28 and creatine kinase activity up to day 7.
      Total white blood cell number, neutrophil percentage, packed cell volume and
      concentrations of haemoglobin, calcium, magnesium (after a transient rise on day
      1), non-esterified fatty acids, bilirubin, creatinine, triiodothyronine and
      thyroxine decreased from birth up to days 42, 56, 28, 28, 21, 84, 14, 14, 7, 14
      and 7, respectively. Basophil percentage and concentrations of beta
      hydroxybutyrate, urea and insulin did not exhibit significant age-dependent
      changes. The behaviour of most traits in the first weeks was the same in suckling
      calves under study as in non-suckling pre-ruminant calves. However, packed cell
      volume, red blood cell number, haemoglobin and plasma iron concentrations were
      higher, whereas glucose and insulin concentrations were lower than normally found
      in veal calves. On the other hand, concentrations of glucose, insulin and insulin
      like growth factor-I in suckling calves in the third month of age were higher
      than can normally be measured in breeding calves.

PMID- 9591475
TI  - Evaluation of a haematological analyser (Sysmex F-800) with equine blood.
AB  - A semiautomatic electronic blood cell counter (Sysmex F-800) was evaluated with
      equine blood, according to the protocol of the International Committee for
      Standardization in Haematology (ICSH, 1984). The precision and overall
      reproducibility were acceptable for all the parameters studied except for the
      platelet count, in which a coefficient of variation of 18.8% and 21.7% was
      obtained for within and between batch precision and 26.76% for overall
      reproducibility. Carry-over for the haematocrit value and platelet count was
      unsatisfactory, thus the use of a blank diluent sample between different analyses
      was necessary. Linearity of the analyser was acceptable in the range studied. A
      total of 100 equine blood samples were studied with the Sysmex F-800 and the
      manual method. The correlations between both Methods were acceptable for all the
      parameters. In the storage study, the red blood cell count and the haemoglobin
      concentration were the parameters with longest stability (72 h) at 4 degrees C
      and 25 degrees C. Platelet count decreased significantly at 3 h post-extraction
      in those samples stored at 4 degrees C. During the evaluation period, Sysmex F
      800 was easy to handle and it is well suited for routine equine blood cell
      analysis.

PMID- 9591476
TI  - Energetics of drug-DNA interactions.
AB  - Understanding the thermodynamics of drug binding to DNA is of both practical and
      fundamental interest. The practical interest lies in the contribution that
      thermodynamics can make to the rational design process for the development of new
      DNA targeted drugs. Thermodynamics offer key insights into the molecular forces
      that drive complex formation that cannot be obtained by structural or
      computational studies alone. The fundamental interest in these interactions lies
      in what they can reveal about the general problems of parsing and predicting
      ligand binding free energies. For these problems, drug-DNA interactions offer
      several distinct advantages, among them being that the structures of many drug
      DNA complexes are known at high resolution and that such structures reveal that
      in many cases the drug acts as a rigid body, with little conformational change
      upon binding. Complete thermodynamic profiles (delta G, delta H, delta S, delta
      Cp) for numerous drug-DNA interactions have been obtained, with the help of high
      sensitivity microcalorimetry. The purpose of this article is to offer a
      perspective on the interpretation of these thermodynamics parameters, and in
      particular how they might be correlated with known structural features.
      Obligatory conformational changes in the DNA to accommodate intercalators and the
      loss of translational and rotational freedom upon complex formation both present
      unfavorable free energy barriers for binding. Such barriers must be overcome by
      favorable free energy contributions from the hydrophobic transfer of ligand from
      solution into the binding site, polyelectrolyte contributions from coupled ion
      release, and molecular interactions (hydrogen and ionic bonds, van der Waals
      interactions) that form within the binding site. Theoretical and semiempirical
      tools that allow estimates of these contributions to be made will be discussed,
      and their use in dissecting experimental data illustrated. This process, even at
      the current level of approximation, can shed considerable light on the drug-DNA
      binding process.

PMID- 9591477
TI  - Predicting sequence-dependent melting stability of short duplex DNA oligomers.
AB  - Many important applications of DNA sequence-dependent hybridization reactions
      have recently emerged. This has sparked a renewed interest in analytical
      calculations of sequence-dependent melting stability of duplex DNA. In
      particular, for many applications it is often desirable to accurately predict the
      transition temperature, or tm of short duplex DNA oligomers (approximately 20
      base pairs or less) from their sequence and concentration. The thermodynamic
      analytical method underlying these predictive calculations is based on the
      nearest-neighbor model. At least 11 sets of nearest-neighbor sequence-dependent
      thermodynamic parameters for DNA have been published. These sets are compared.
      Use of the nearest-neighbor sets in predicting tm from the DNA sequence is
      demonstrated, and the ability of the nearest-neighbor parameters to provide
      accurate predictions of experimental tm's of short duplex DNA oligomers is
      assessed.

PMID- 9591479
TI  - DNA condensation by multivalent cations.
AB  - In the presence of multivalent cations, high molecular weight DNA undergoes a
      dramatic condensation to a compact, usually highly ordered toroidal structure.
      This review begins with an overview of DNA condensation: condensing agents,
      morphology, kinetics, and reversibility, and the minimum size required to form
      orderly condensates. It then summarizes the statistical mechanics of the collapse
      of stiff polymers, which shows why DNA condensation is abrupt and why toroids are
      favored structures. Various ways to estimate or measure intermolecular forces in
      DNA condensation are discussed, all of them agreeing that the free energy change
      per base pair is very small, on the order of 1% of thermal energy. Experimental
      evidence is surveyed showing that DNA condensation occurs when about 90% of its
      charge is neutralized by counterions. The various intermolecular forces whose
      interplay gives rise to DNA condensation are then reviewed. The entropy loss upon
      collapse of the expanded wormlike coil costs free energy, and stiffness sets
      limits on tight curvature. However, the dominant contributions seem to come from
      ions and water. Electrostatic repulsions must be overcome by high salt
      concentrations or by the correlated fluctuations of territorially bound
      multivalent cations. Hydration must be adjusted to allow a cooperative
      accommodation of the water structure surrounding surface groups on the DNA
      helices as they approach. Undulations of the DNA in its confined surroundings
      extend the range of the electrostatic forces. The condensing ions may also subtly
      modify the local structure of the double helix.

PMID- 9591478
TI  - Energetics of the lattice: packing elements in crystals of four-stranded
      intercalated cytosine-rich DNA molecules.
AB  - Condensation of single molecules from solution into crystals represents a
      transition between distinct energetic states. In solution, the atomic
      interactions within the molecule dominate. In the crystalline state, however, a
      set of additional interactions are formed between molecules in close contact in
      the lattice--these are the packing interactions. The crystal structures of
      d(CCCT), d(TAACCC), d(CCCAAT), and d(AACCCC) have in common a four-stranded
      intercalated cytosine segment, built by stacked layers of cytosine.cytosine+
      (C.C+) base pairs coming from two parallel duplexes that intercalate into each
      other with opposite polarity. The intercalated cytosine segments in these
      structures are similar in their geometry, even though the sequences crystallized
      in different space groups. In the crystals, adenine and thymine residues of the
      sequences are used to build the three-dimensional crystal lattice by elaborately
      interacting with symmetry-related molecules. The packing elements observed
      provide novel insight about the copious ways in which nucleic acid molecules can
      interact with each other--for example, when folded in more complicated higher
      order structures, such as mRNA and chromatin.

PMID- 9591480
TI  - The question of long-range allosteric transitions in DNA.
AB  - The question of long-range allosteric transitions of DNA secondary structure and
      their possible involvement in transcriptional activation is discussed in the
      light of new results. A variety of recent evidence strongly supports a
      fluctuating long-range description of DNA secondary structure. Balanced
      equilibria between two or more different secondary structures, and the occurrence
      of very large domain sizes, have been documented in several instances. Long-range
      allosteric effects stemming from changes in sequence or secondary structure over
      a small region of the DNA have been observed to extend over distances up to
      hundreds of base pairs in some cases. The discovery that coherent bending strain
      beyond a threshold level in small (N < or = 250 base pairs (bp)] circular DNAs
      significantly alters the DNA secondary structure has important implications,
      especially for transcriptional activators that either bend the DNA directly or
      are involved in the formation of DNA loops of sufficiently small size (N < or =
      250 bp). Whether the RNA polymerase is activated primarily via protein: protein
      contacts, as is widely believed, or instead via a bend-induced allosteric
      transition of the DNA in such a small loop, is now an open question. Binding of
      the transcriptional activator Sp1 to linear DNA induces a remarkably long-range
      change in its secondary structure, and catabolite activator protein binding to a
      supercoiled DNA behaves similarly, though possibly for different reasons.
      Compelling evidence for a bend-induced long-range structural transmission effect
      of the transcriptional activator integration host factor on RNA polymerase
      activity was recently reported. These results may augur a new paradigm in which
      allosteric transitions of duplex DNA, as well as of the proteins, are involved in
      the regulation of transcription.

PMID- 9591481
TI  - Measuring the thermodynamics of RNA secondary structure formation.
AB  - The thermodynamics of RNA secondary structure formation in small model systems
      provides a database for predicting RNA structure from sequence. Methods for
      making these measurements are reviewed with emphasis on optical methods and
      treatment of experimental errors. Analysis of experimental results in terms of
      simple nearest-neighbor models is presented. Some measured sequence dependences
      of non-Watson-Crick motifs are discussed.

PMID- 9591482
TI  - Conscious sedation for in vitro fertilization.
AB  - OBJECTIVE: To review the principles and practice of the use of conscious sedation
      for IVF. DESIGN: The pertinent literature was reviewed and recommendations are
      provided. RESULT(S): Conscious sedation appears to be the most commonly used
      method of pain relief for transvaginal retrieval of oocytes. Conscious sedation
      does not require the presence of an anesthesiologist and can be done in
      freestanding clinics. Agents commonly used include opioids in combination with
      benzodiazepines. This combination minimizes pain, decreases anxiety, and provides
      sedation and some amnesia. Adjuvants such as promethazine and hydroxyzine can
      also be used but often are not needed. Conscious sedation is well tolerated by
      patients and does not require highly specialized equipment. However, there are
      specific safeguards that should be followed. Only a few toxicity studies have
      been performed, but they are reassuring because they have not found significant
      effects on fertilization or cleavage. CONCLUSION(S): Conscious sedation appears
      to be a safe and cost-effective method of providing analgesia and anesthesia for
      transvaginal retrieval of oocytes.

PMID- 9591483
TI  - Why we believe there should be a gamete registry.

PMID- 9591484
TI  - Gamete registry? A Trojan horse from those seeking regulation.

PMID- 9591485
TI  - Lack of association between antiphospholipid antibodies and first-trimester
      spontaneous abortion: prospective study of pregnancies detected within 21 days of
      conception.
AB  - OBJECTIVE: To determine the role of antiphospholipid antibodies and
      anticardiolipin antibodies in first-trimester losses, addressing experimental
      pitfalls that preclude excluding the possibility that these antibodies reflect
      merely the selection bias of studying couples only after they have already
      experienced losses. DESIGN: Given that retrospective studies cannot exclude the
      possibility that such antibodies arise as a result of the fetal death, blood
      samples were obtained either before pregnancy or very early in pregnancy. Sera
      were obtained within 21 days of conception. SETTING: Multicenter university-based
      hospitals (National Institute of Child Health and Human Development collaborative
      study). PATIENT(S): Subjects for the current study were 93 women who later
      experienced pregnancy loss (48 diabetic; 45 nondiabetic), matched 2:1 with 190
      controls (93 diabetic and 97 nondiabetic) who subsequently had normal live-born
      offspring. INTERVENTION(S): Sera from these 283 women were analyzed for
      antiphospholipid antibodies by enzyme immunoassay. In 260 of the 283 women (87
      with pregnancy losses; 173 with live-born infants), sera were also available to
      perform assays for anticardiolipin antibodies by enzyme immunoassay. MAIN OUTCOME
      MEASURE(S): Pregnancy losses. RESULT(S): No association was observed between
      pregnancy loss and the presence of antiphospholipid antibodies or anticardiolipin
      antibodies. Levels of antiphospholipid antibodies were 6-19 PL/mL in 62.4% of the
      pregnancies that ended in losses and > or = 20 PL/mL in 5.4%; among pregnancies
      resulting in live-born infants, the percentages were 56.8% and 6.8%,
      respectively. Of the pregnancies that ended in a loss, 5.7% had anticardiolipin
      antibodies > or = 16 GPL/mL, compared with 5.2% of those ending in a live birth.
      CONCLUSION(S): This prospective study suggests that anticardiolipin antibodies
      and antiphospholipid antibodies are not associated with an increased risk for
      first-trimester pregnancy loss.

PMID- 9591486
TI  - Women of reproductive age with endometriosis are not osteopenic.
AB  - OBJECTIVE: To determine whether women of reproductive age with endometriosis are
      osteopenic and whether bone density decreases with higher stages of
      endometriosis. DESIGN: A multicenter cross-sectional study was performed.
      SETTING: Thirty-nine gynecological clinics in the United States, Canada, and
      Puerto Rico. PATIENT(S): Two hundred forty-one women of reproductive age with
      laparoscopically proved endometriosis. INTERVENTION(S): Diagnostic laparoscopy,
      bone densitometry. MAIN OUTCOME MEASURE(S): Endometriosis stages according to the
      criteria of the American Society for Reproductive Medicine, lumbar spine bone
      mineral density (L2-L4) as measured by dual-energy x-ray absorptiometry.
      RESULT(S): The mean lumbar spine bone mineral density, as well as the
      distribution of bone mineral density, of the women with endometriosis was similar
      to that of a normal population. There were no significant differences between
      endometriosis stage groups I-IV regarding bone mineral density as well as body
      weight, body mass index, and height. CONCLUSION(S): Women of reproductive age
      with endometriosis are not osteopenic. More advanced stages of endometriosis are
      not associated with a decrease in lumbar spine bone mineral density.

PMID- 9591487
TI  - Cessation of gonadotropin-releasing hormone agonist therapy combined with high
      dose gonadotropin stimulation yields favorable pregnancy results in low
      responders.
AB  - OBJECTIVE: To evaluate the pregnancy results of an ovarian hyperstimulation
      protocol for IVF-ET that combines GnRH agonist down-regulation, cessation of GnRH
      agonist therapy with the onset of menstruation, and high-dose gonadotropin
      administration in low responders. DESIGN: Prospective analysis. SETTING: Academic
      IVF program. PATIENT(S): One hundred eighty-two low responders undergoing 224 IVF
      ET cycles. INTERVENTION(S): Down-regulation was obtained with the administration
      of leuprolide acetate beginning in the midluteal phase and ending with the onset
      of menses. Daily administration of 6 ampules of FSH alone or in combination with
      hMG was initiated on cycle day 3. MAIN OUTCOME MEASURE(S): Stimulation
      characteristics and pregnancy rates (PRs) were compared between fresh cycles in
      which pure FSH alone was used and 35 cycles in which a combination of FSH and hMG
      was administered. RESULT(S): The clinical PR per transfer, the ongoing PR per
      transfer, and the implantation rate were 32%, 24%, and 9%, respectively. No
      differences were noted between cycles in which pure FSH alone was used in
      comparison with cycles in which a combination of FSH and hMG was administered.
      CONCLUSION(S): Short-term ovarian suppression begun in the luteal phase and
      discontinued with the onset of menses followed by high-dose stimulation with
      gonadotropins yields favorable pregnancy results in low responders.

PMID- 9591488
TI  - Characteristics of consecutive in vitro fertilization cycles among patients
      treated with follicle-stimulating hormone (FSH) and human menopausal gonadotropin
      versus FSH alone.
AB  - OBJECTIVE: To compare the endocrine responses of patients who first received hMG
      plus FSH, then were treated in a subsequent cycle with FSH alone. DESIGN:
      Retrospective study. SETTING: An academic research environment. PATIENT(S):
      Ninety-six women with pituitary down-regulation who underwent two sequential IVF
      treatments, the first with combined hMG and FSH and the second with FSH alone.
      MAIN OUTCOME MEASURE(S): Duration of stimulation, serum estradiol level on the
      day of hCG administration, amount of gonadotropin used, number of oocytes
      retrieved, number of oocytes fertilized, and selected preembryo morphologic
      features. RESULT(S): No difference in the mean duration of stimulation was
      observed between the treatment cycles among patients who received hMG and FSH
      (11.9 days) followed by FSH alone (11.7 days). The mean number of oocytes
      retrieved, the mean number of oocytes fertilized, the percentage of preembryo
      fragmentation, and the preembryo cell number at transfer did not differ
      significantly between the stimulation protocols. The cumulative amount of
      gonadotropin used during stimulation was slightly greater in the cycles
      stimulated with FSH alone, but this difference was not significant (29.4 ampules
      of hMG plus FSH versus 31.8 ampules of FSH alone). Serum estradiol levels
      measured on the day of hCG administration during stimulation with hMG and FSH
      (1,382 pg/mL) were higher than those measured during stimulation with FSH alone
      (1,149 pg/mL). CONCLUSION(S): Follicular response and preembryo quality were not
      significantly different when patients were treated first with hMG and FSH and
      then with FSH alone in a subsequent cycle. Similarities in ovarian response and
      preembryo characteristics, as well as differences in estradiol patterns seen in
      each stimulation setting, should be anticipated when patients receive these
      protocols.

PMID- 9591489
TI  - Local side effects of subcutaneous and intramuscular urinary gonadotropins for
      ovarian stimulation in in vitro fertilization: a prospective, randomized study.
AB  - OBJECTIVE: To compare the incidence and severity of local side effects of urinary
      derived gonadotropins administered s.c. and i.m.. DESIGN: Prospective randomized
      study of women undergoing IVF treatment. SETTING: Tertiary referral center for
      assisted reproduction. PATIENT(S): A total of 71 patients were randomized to
      receive gonadotropins by the s.c. (n = 41) or i.m. (n = 30) route.
      INTERVENTION(S): One cycle of IVF with gonadotropins administered either s.c. or
      i.m. for ovarian stimulation. MAIN OUTCOME MEASURE(S): Incidence and severity of
      local side effects, such as redness, itching, swelling, pain, and bruising.
      RESULT(S): Pain was the most common side effect, with 55.3% and 70.1% of i.m. and
      s.c. injections, respectively, resulting in pain. There were no statistically
      significant differences in the incidence of itching or bruising after i.m. and
      s.c. injections. Although there was a higher incidence of redness and swelling in
      the s.c. group compared with the i.m. group, most cases were classified as mild.
      CONCLUSION(S): There was a significantly higher incidence of some local side
      effects after s.c. gonadotropin administration but most of these were mild and
      well tolerated by patients.

PMID- 9591490
TI  - Sonohysterographic screening before in vitro fertilization.
AB  - OBJECTIVE: To evaluate the use of sonohysterography for uterine screening before
      IVF. DESIGN: Prospective screening with sonohysterography and comparison with
      available hysterosalpingographic and hysteroscopic evaluations. SETTING: Private
      practice. PATIENT(S): Seventy-two women undergoing IVF-ET using their own or
      donor eggs. INTERVENTION(S): Sonohysterography was performed by instilling saline
      into the uterine cavity through an intracervical balloon catheter; there was
      concurrent vaginal sonographic visualization in all cases. MAIN OUTCOME
      MEASURE(S): Sonohysterographic findings and pregnancy rates. RESULT(S): Cavitary
      lesions were detected in 8 (11.1%) of 72 sonohysterographic examinations. Six of
      8 cases were confirmed and treated by hysteroscopy. After sonohysterographic
      evaluation, 35 (48.6%) of 72 patients conceived, resulting in 25 ongoing or
      delivered pregnancies, 5 chemical pregnancies, and 5 spontaneous abortions. No
      statistically significant difference was observed in the pregnancy outcome for
      patients undergoing IVF who had sonohysterography compared with that for patients
      undergoing IVF during the same period who previously had a uterine evaluation by
      a different method. The estimated cost savings per patient undergoing
      sonohysterography instead of in-office hysteroscopy was $275. CONCLUSION(S):
      Sonohysterography offers advantages over in-office hysteroscopy and
      hysterosalpingography for evaluation of the uterus before IVF.

PMID- 9591491
TI  - Multifetal pregnancy reduction: a possible risk factor for periventricular
      leukomalacia in premature newborns.
AB  - OBJECTIVE: To investigate the possible role of multifetal pregnancy reduction as
      a risk factor for the development of periventricular leukomalacia, which has been
      associated with prematurity and twin pregnancies. DESIGN: A case-control study.
      SETTING: In Vitro Fertilization Unit and Intensive Care Nursery of the Tel Aviv
      Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): A total of 1,401
      consecutive preterm infants who were born between January 1, 1994, and December
      31, 1995. INTERVENTION(S): Cranial ultrasonographic evaluation of each infant
      within 3 days of birth. MAIN OUTCOME MEASURE(S): Premature infants who developed
      periventricular leukomalacia (cases) were compared with premature infants who did
      not develop this disorder (controls) when multifetal pregnancy reduction was
      considered. RESULT(S): Fourteen premature infants developed periventricular
      leukomalacia. Of these, 28.6% (4 infants) were exposed to multifetal pregnancy
      reduction, compared with 1.9% of the controls, giving an odds ratio (OR) of 20.9
      (95% confidence interval [CI] 5.5-79.4). Adjustment of this OR for IVF treatment
      (OR, 18.6; 95% CI, 1.8-140.3), twinning (OR, 6.3; 95% CI, 1.3-30.3), and for both
      IVF treatment and twinning simultaneously (OR, 8.5; 95% CI, 1.7-42.2) did not
      explain all the observed associations between periventricular leukomalacia and
      multifetal pregnancy reduction. CONCLUSION(S): Our data suggest that multifetal
      pregnancy reduction may be an additional risk factor for periventricular
      leukomalacia among premature infants, regardless of twinning.

PMID- 9591492
TI  - Role of the ovary in the adrenal androgen excess of hyperandrogenic women.
AB  - OBJECTIVE: To test the hypothesis that ovarian hormones in women with
      hyperandrogenism alter adrenocortical steroidogenesis. DESIGN: Combination of two
      prospective studies. SETTING: Academic medical centers. PATIENT(S): Eighteen
      hyperandrogenic patients demonstrating hirsutism with either hyperandrogenemia,
      oligomenorrhea, or both. Eighteen healthy nonhirsute eumenorrheic untreated women
      served as controls. INTERVENTIONS: Blood sampling basally and after acute adrenal
      stimulation with ACTH, before and after 20-24 weeks of leuprolide administration.
      Nine patients also received 0.625 mg/d of oral conjugated esterified estrogens
      and 10 mg of medroxyprogesterone acetate days 1-12 of the month (i.e., estrogen
      replacement therapy [ERT]), whereas the remaining nine did not. MAIN OUTCOME
      MEASURE(S): Before and after the administration of the GnRH agonist (GnRH-a), the
      basal concentrations of DHEAS; and the levels of androstenedione (A4), DHEA,
      androstenediol, 11 beta-hydroxyandrostenedione (11-OHA4), and cortisol before and
      60 minutes after acute adrenal stimulation, were measured. RESULT(S): Levels of
      DHEAS, androstenediol, and 11-OHA4 decreased by 15%-30%, regardless of whether
      patients initially had or did not have DHEAS excess. However, only
      hyperandrogenic patients with elevated levels of DHEAS showed a significant
      decrease in basal DHEA levels. No statistically significant difference in the
      response of either androgen to ACTH (1-24) stimulation was noted with ovarian
      suppression, regardless of initial DHEAS level or use of ERT. CONCLUSION(S): We
      found no evidence that ovarian hormone secretion affected adrenal
      steroidogenesis, and those women with the highest adrenal androgen levels had the
      least response to GnRH-a suppression. These findings further support the concept
      of an intrinsic, and possibly primary, abnormality of adrenocortical
      steroidogenesis in a subset of hyperandrogenic women that is independent of
      ovarian abnormalities.

PMID- 9591493
TI  - Myometrial scoring: a new technique for the management of severe Asherman's
      syndrome.
AB  - OBJECTIVE: To describe a new hysteroscopic technique for the management of severe
      Asherman's syndrome. DESIGN: Prospective observational study. SETTING: Volunteers
      in an academic research environment. PATIENT(S): Seven patients with secondary
      infertility associated with amenorrhea or oligomenorrhea secondary to severe
      Asherman's syndrome. INTERVENTION(S): Six to eight longitudinal incisions were
      made into the myometrium extending from the uterine fundus to the isthmus with a
      resectoscope fitted with a Collins knife electrode. MAIN OUTCOME MEASURE(S):
      Restoration of menses, symptomatic relief, and postoperative reproductive
      performance. RESULT(S): The amount of menstrual bleeding increased in all cases,
      including two women who were amenorrheic before their surgery. Pelvic pain
      decreased in two of the four symptomatic cases. Three to four months after
      surgery, hysteroscopy showed a normal sized uterine cavity in five cases. After a
      median follow-up of 12 months, three women conceived four pregnancies, including
      a missed abortion, a tubal abortion, an ongoing pregnancy currently at 7 weeks'
      gestation, and one child delivered at 36 weeks gestation after premature rupture
      of the membranes. CONCLUSION(S): Hysteroscopic myometrial scoring enlarges
      uterine cavity size in cases of severe Asherman's syndrome and improves menstrual
      function. Reproductive performance seems to be improved also, but longer follow
      up is required.

PMID- 9591494
TI  - Unexpected vaginal bleeding and associated gynecologic care in postmenopausal
      women using hormone replacement therapy: comparison of cyclic versus continuous
      combined schedules.
AB  - OBJECTIVE: To measure gynecologic resources required to care for women who have
      unexpected vaginal bleeding while using hormone replacement therapy (HRT).
      DESIGN: A retrospective cohort study based on review of medical records. SETTING:
      A large health maintenance organization. PATIENT(S): We studied 284 women using
      continuous combined HRT and 306 women receiving cyclic HRT. MAIN OUTCOME
      MEASURE(S): We noted episodes of unexpected vaginal bleeding and associated
      clinic visits and gynecologic procedures recorded during a mean follow-up period
      of 2 years. RESULT(S): Among women using cyclic HRT for the first time, 38.3% had
      > or = 1 visit for unexpected bleeding and 12.3% had > or = 1 endometrial biopsy.
      Among women starting continuous combined HRT, 41.6% had > or = 1 visit for
      unexpected bleeding and 20.1% had > or = 1 endometrial biopsy. After adjusting
      for potential confounding variables, we found that recipients of cyclic and
      continuous combined HRT had similar risks of unexpected bleeding and endometrial
      biopsy. However, among women continuing HRT for >2 years, those using the
      continuous combined regimen had somewhat lower rates of unexpected bleeding (22.3
      events per 100 patient-years) and endometrial biopsy (10.3 events per 100 patient
      years) than those using the cyclic regimen (37.8 episodes of unexpected bleeding
      per 100 patient-years and 13.9 endometrial biopsies per 100 patient-years).
      CONCLUSION(S): Unexpected vaginal bleeding and the gynecologic resources required
      to manage it decreased after 2 years in women using continuous combined HRT but
      did not decline among those using cyclic HRT.

PMID- 9591495
TI  - Mammographic changes in women receiving tibolone therapy.
AB  - OBJECTIVE: To investigate the effects of tibolone therapy for menopausal symptoms
      on mammographic findings and to identify any association between mammographic
      changes and the demographic and hormonal characteristics of women receiving
      tibolone. DESIGN: A prospective study. SETTING: A university hospital.
      PATIENT(S): Seventy-five women who were in the climacteric or postmenopausal
      period were recruited, and 25 of them were followed up for 24 months.
      INTERVENTION(S): After high-resolution mammographies were performed and blood
      samples were collected, tibolone (2.5 mg/d) was administered orally to all
      patients. At the end of the 24-month follow-up period, blood samples were
      collected again and mammographies were repeated. MAIN OUTCOME MEASURE(S): Serum
      levels of LH, FSH, prolactin, estradiol, testosterone, and DHEAS were determined
      from the collected samples, and mammographies were interpreted. RESULT(S): At the
      end of the 24-month follow-up period, mammographic changes were observed in only
      two women (8%). Women who had no change in mammography constituted group I (n =
      23). Women who had a change constituted group II (n = 2). Although the initial
      hormone levels were not different, the increase in serum DHEAS in group I was
      significantly higher than in group II (z = 2.30, P = 0.021). CONCLUSION(S): The
      frequency of mammographic changes in women receiving tibolone therapy was found
      to be 8% at the end of the 24-month follow-up. The serum DHEAS level may be an
      important hormonal marker complementary to mammographic screening for women
      receiving tibolone therapy. We strongly believe that tibolone is safe in terms of
      mammographic changes in postmenopausal women.

PMID- 9591496
TI  - Postmenopausal oral 17beta-estradiol continuously combined with dydrogesterone
      reduces fasting serum homocysteine levels.
AB  - OBJECTIVE: To investigate the effects of oral 17beta-estradiol administration
      continuously combined with dydrogesterone on fasting serum total homocysteine
      levels in postmenopausal women. DESIGN: Randomized, double-blind study. SETTING:
      Gynecologic outpatient department of a university hospital. PATIENT(S): One
      hundred thirty-five healthy, nonhysterectomized postmenopausal women.
      INTERVENTION(S): Oral micronized 17beta-estradiol (2 mg/d) continuously combined
      with one of four dosages of dydrogesterone (2.5 mg [n = 41], 5 mg [n = 38], 10 mg
      [n = 37], or 15 mg [n = 19]) was given for 6 months. MAIN OUTCOME MEASURE(S):
      Fasting serum total homocysteine concentrations. RESULT(S): The mean fasting
      serum total homocysteine concentrations in the overall study population decreased
      significantly (by 13.5%) after the first 3 months of treatment and remained
      unchanged thereafter. No influence of dydrogesterone dosage was found. The
      greatest reduction in total homocysteine concentration was obtained in women with
      the highest baseline levels. CONCLUSION(S): Continuously combined hormone
      replacement therapy lowers fasting serum total homocysteine levels significantly
      in postmenopausal women. This decrease may be one of the mechanisms that underlie
      the cardioprotective effects of postmenopausal hormone replacement therapy.

PMID- 9591497
TI  - The long-term effects of oral and transdermal postmenopausal hormone replacement
      therapy on nitric oxide, endothelin-1, prostacyclin, and thromboxane.
AB  - OBJECTIVE: Oral postmenopausal hormone replacement therapy (HRT) decreases the
      risk of cardiovascular disorders, but the mechanisms of this protection are
      largely unknown. We compared the long-term effects of sequential oral HRT and
      transdermal HRT on vasodilatory nitric oxide and prostacyclin as well as
      vasoconstrictive endothelin- and thromboxane A2, all of which may be factors in
      the protective effect of HRT against cardiovascular disorders. DESIGN:
      Prospective, randomized study. SETTING: Department of Obstetrics and Gynecology
      at a university hospital. PATIENT(S): Fifty-two healthy postmenopausal female
      nonsmokers (n = 42) or smokers (n = 10) who had climacteric symptoms.
      INTERVENTION(S): The women received either oral HRT (2 mg of estradiol on days 1
      12, 2 mg of estradiol plus 1 mg of norethisterone acetate on days 13-22, and 1 mg
      of estradiol on days 23-28; n = 21) or transdermal HRT (50 microg/d of estradiol
      on days 1-28 followed by 250 microg/d of norethisterone acetate on days 14-28; n
      = 21) for 1 year. Ten female smokers received transdermal HRT for 1 year. MAIN
      OUTCOME MEASURE(S): Plasma levels of nitrate as an index of nitric oxide
      production, endothelin-1, and urinary output of the prostacyclin metabolite (2,3
      dinor-6-keto-PGF1alpha) and that of the thromboxane A2 metabolite (2,3
      dinorthromboxane B2) were measured before and during the combined phases of the
      2nd, 6th, and 12th treatment months. RESULT(S): Both regimens increased plasma
      estradiol levels and alleviated vasomotor symptoms. Neither regimen caused
      significant changes in nitrate, endothelin-1, prostacyclin, or thromboxane A2 in
      nonsmoking women. Female smokers had significantly higher levels of endothelin-1,
      which were significantly reduced by transdermal HRT at 6 months of treatment.
      CONCLUSION(S): Nitric oxide, endothelin-1, prostacyclin, and thromboxane A2 are
      not of primary importance in the protective effect of sequential oral HRT against
      cardiovascular disorders in otherwise healthy nonsmoking postmenopausal women. In
      this regard, transdermal HRT appears comparable to oral HRT. Postmenopausal
      female smokers have high levels of endothelin-1 that are reduced by transdermal
      HRT.

PMID- 9591498
TI  - Why cancer patients request disposal of cryopreserved semen specimens
      posttherapy: a retrospective study.
AB  - OBJECTIVE: To determine why patients with cancer stop storing semen in a sperm
      bank program. DESIGN: Retrospective study. SETTING: Hospital andrology
      laboratory. PATIENT(S): Cancer patients (n = 56) who discontinued sperm storage.
      INTERVENTION(S): A database of 342 patients with cryopreserved sperm was searched
      for disease diagnosis, marital status before and after diagnosis, type of
      therapy, number of specimens banked, interval between diagnosis and sperm
      banking, and postthaw semen characteristics. Patients discontinuing storage were
      surveyed. MAIN OUTCOME MEASUREMENT(S): Reasons for discontinuing storage and
      clinical correlation of the decision. RESULT(S): Reasons included patient death
      (n = 21); fertility but no plans for more children (n = 23); good sperm quality
      (n = 8); and no plans to have children (n = 4). Patients were similar in age,
      number of specimens, and interval between diagnosis and treatment, but they
      showed significant differences in type of treatment and time in the program. Cost
      of cryopreservation and specimen storage was not cited. CONCLUSION(S): Most
      patients decided to discontinue sperm banking because either they regained
      fertility or had improved semen quality. Sperm banking should be strongly
      recommended for all patients with malignant diseases who may wish to have
      children, even if they eventually decide that the specimens are not needed.

PMID- 9591499
TI  - Validity and cost-effectiveness of antisperm antibody testing before in vitro
      fertilization.
AB  - OBJECTIVE: To determine the usefulness of and cost-effectiveness of antisperm
      antibody testing in the prediction of poor fertilization rates in couples
      undergoing IVF. DESIGN: Retrospective cohort study. SETTING: A hospital-based
      reproductive endocrinology and infertility practice. PATIENT(S): Male partners of
      251 couples undergoing IVF between 1992 and 1997. MAIN OUTCOME MEASURE(S):
      Fertilization rates in couples undergoing conventional IVF. RESULT(S): One
      hundred nineteen couples were evaluated for antisperm antibodies; fertilization
      rates were similar in those couples whose husbands were and were not tested (64%
      versus 68%). Antisperm antibodies were detected in 16 men. Four (25%) of the 16
      couples whose husbands had antisperm antibodies fertilized < or = 50% of oocytes,
      compared with 31 (30%) of the 103 couples whose husbands did not have these
      antibodies. Overall, 21 couples (8.4%) experienced complete fertilization
      failure. In a program that included antisperm antibody testing for selected
      couples and intracytoplasmic sperm injection (ICSI) for those who tested
      positive, it would cost $11,735 to prevent a fertilization failure (assuming ICSI
      were 100% effective), whereas it would cost $9,250 to perform ICSI in a second
      IVF cycle for those who initially failed. CONCLUSION(S): In this practice
      setting, antisperm antibody testing has low sensitivity in predicting low or no
      fertilization and does not appear to be cost-effective when selectively ordered
      as part of an IVF workup.

PMID- 9591500
TI  - Mutation frequency of cystic fibrosis transmembrane regulator is not increased in
      oligozoospermic male candidates for intracytoplasmic sperm injection.
AB  - OBJECTIVE: To examine the frequency of anomalies of the vas deferens and the
      frequency of mutations of the cystic fibrosis transmembrane regulator (CFTR) gene
      in male candidates for intracytoplasmic sperm injection (ICSI) who had severe
      oligoasthenoteratozoospermia. DESIGN: The clinical data for male candidates for
      ICSI were studied. The three most frequent cystic fibrosis (CF)-causing CFTR
      mutations in the Dutch population (deltaF508, A455E, and G542X) and the three
      most frequent CFTR mutations potentially causing congenital bilateral absence of
      the vas deferens (CBAVD) in the Dutch population (deltaF508, R117H, and IVS8-5T)
      were analyzed. Delta I507 is also detected by the deltaF508 test. Samples of DNA
      from patients identified as CFTR mutation carriers were subjected to denaturing
      gradient gel electrophoresis analysis with use of a two-dimensional
      electrophoretic technique. SETTING: University-based center for reproductive
      medicine and clinical genetics. PATIENT(S): Male candidates for ICSI who had
      oligoasthenoteratozoospermia and no history of operative sterilization and
      refertilization. Males with a chromosomal aberration or a Y-chromosome
      microdeletion were excluded. INTERVENTION(S): Semen and blood samples were
      collected from the patients at their first visit to the clinic. MAIN OUTCOME
      MEASURE(S): Frequency of anomalies of the vas deferens and frequency of mutations
      of the CFTR gene in male candidates for ICSI who had
      oligoasthenoteratozoospermia. RESULT(S): None of the patients had abnormalities
      of the vas deferens at physical examination. In 4 of the 150 chromosomes (75
      patients), a CFTR mutation was found, yielding a CFTR mutation frequency of 2.7%
      (95% confidence interval, 1.0-6.7%). None of the patients had two CFTR mutations.
      CONCLUSION(S): The frequency of congenital abnormalities of the vas deferens in
      patients with oligoasthenoteratozoospermia is low. The frequencies of the CFTR
      mutations identified in this cohort did not differ significantly from the
      frequencies found in the normal Dutch population.

PMID- 9591501
TI  - Chromosome abnormalities in embryos obtained after conventional in vitro
      fertilization and intracytoplasmic sperm injection.
AB  - OBJECTIVE: To compare the rate of numerical chromosome abnormalities in embryos
      derived from bipronucleated zygotes produced by intracytoplasmic sperm injection
      (ICSI) and conventional IVF. DESIGN: Embryos were classified by maternal age and
      morphological and developmental characteristics to avoid bias when comparing
      chromosome abnormalities in ICSI and IVF embryos. SETTING: The Institute for
      Reproductive Medicine and Science of Saint Barnabas Medical Center, West Orange,
      New Jersey. PATIENT(S): Seventy-nine couples undergoing IVF and 53 couples
      undergoing ICSI. INTERVENTION(S): Embryos donated for research were fully
      biopsied, and their cells were analyzed by fluorescence in situ hybridization
      with specific probes for chromosomes X, Y, 13, 18, and 21 and some with also a
      probe for chromosome 16. MAIN OUTCOME MEASURE(S): Embryo chromosome
      abnormalities. RESULT(S): A total of 245 embryos obtained through conventional
      IVF and 136 embryos obtained through ICSI were analyzed. There were no
      statistical differences between the rates of numerical chromosomal abnormalities
      detected in the IVF (61%) and ICSI (52%) embryos analyzed. Regarding gonosomal
      aneuploidy, the same rate was found in both ICSI (1%) and IVF groups (2%).
      CONCLUSION(S): If the parents are chromosomally normal, the results indicate
      that, at the embryo level and before any embryo selection has occurred in utero,
      ICSI does not produce more numerical chromosomal abnormalities than conventional
      IVF.

PMID- 9591502
TI  - Vectorial secretion of vascular endothelial growth factor by polarized human
      endometrial epithelial cells.
AB  - OBJECTIVE: To analyze directional vascular endothelial growth factor (VEGF)
      secretion in polarized human endometrial epithelial cell cultures. VEGF has
      distinct distribution patterns in human endometrium. Stromal cells are diffusely
      positive for VEGF messenger RNA and protein, whereas glandular epithelium shows
      focal VEGF immunostaining at the apical surface. The epithelial distribution
      suggests that VEGF is secreted into gland lumina, potentially influencing the
      nutrition and/or apposition of the developing blastocyst. DESIGN: Controlled in
      vitro study of protein secretion by polarized endometrial epithelial cells
      established on polyethylene filters. SETTING: University hospital. PATIENT(S):
      Endometrial biopsies were obtained from healthy, ovulatory women undergoing
      elective surgery. INTERVENTION(S): Primary endometrial epithelial cells were
      cultured. MAIN OUTCOME MEASURE(S): VEGF mRNA and protein production were measured
      in polarized cells. The vectorial secretion of VEGF was determined. RESULT(S):
      VEGF production by endometrial epithelial cells was verified by Northern blotting
      and immunoassays of conditioned media. The mean (+/-SD) apical secretion of VEGF
      was 3.9 +/- 1.4 ng per 10(5) cells every 48 hours and the mean (+/-SD) basal
      secretion was 0.8 +/- 0.2 ng per 10(5) cells every 48 hours. In contrast, the
      apical and basal secretion of a soluble cellular isoform of fibronectin were 2.76
      +/- 0.96 ng per 10(5) cells every 48 hours and 2.64 +/- 1.79 ng per 10(5) cells
      every 48 hours, respectively. CONCLUSION(S): VEGF is secreted preferentially into
      the lumina of endometrial glands. Apical VEGF may be an endometrial signal for
      blastocyst development or implantation.

PMID- 9591503
TI  - Gonadotropin-releasing hormone agonist (GnRH-a) therapy alters activity of
      plasminogen activators, matrix metalloproteinases, and their inhibitors in rat
      models for adhesion formation and endometriosis: potential GnRH-a-regulated
      mechanisms reducing adhesion formation.
AB  - OBJECTIVE: To evaluate the effects of a gonadotropin-releasing hormone agonist
      (GnRH-a) on plasminogen activator (PA), matrix metalloproteinase (MMP),
      plasminogen activator inhibitor (PAI) and matrix metalloproteinase inhibitor
      (MMPI) activities in peritoneal fluid relative to GnRH-a-induced reduction of
      adhesion formation. DESIGN: Continuation of prospective randomized study using
      surgical models for adhesion formation. SETTING: Department of Obstetrics and
      Gynecology research laboratory at the University of Missouri School of Medicine.
      PATIENT(S): Forty reproductively cycling female Sprague-Dawley rats.
      INTERVENTION(S): Female rats were injected with depot GnRH-a or diluent and
      randomly assigned to adhesion and endometriosis surgeries. Peritoneal fluid was
      collected prior to (time 1) and 7 weeks from (time 2) initial surgery. MAIN
      OUTCOME MEASURE(S): Peritoneal fluid was analyzed for PA, PAI, MMP, and MMPI
      activities. RESULT(S): At time 1, MMP and MMPI activities were similar in all
      rats; however, PA and PAI activities were less in rats pretreated with GnRH-a
      than with diluent. Between time 1 and time 2, GnRH-a-treated rats showed an
      increase in PAI and MMPI activities without significant changes in PA or MMP
      activities, whereas rats receiving diluent showed a significant increase in PAI
      and MMP activities but no significant changes in PA or MMPI activities. At time
      2, rats receiving GnRH-a had less PA and MMP activities than those receiving
      diluent. Adhesion scores showed a positive correlation with MMP activity.
      CONCLUSION(S): In the absence of GnRH-a therapy, surgical tissue manipulation
      increased peritoneal fluid MMP and PAI activity. Gonadotropin-releasing hormone
      agonist therapy decreased PA and MMP activities and also increased PAI and MMPI
      activities. This GnRH-a-induced shift to a less invasive phenotype may alter
      fibrinolysis and extracellular matrix remodeling and thereby play a role in the
      mechanism of GnRH-a-induced reduction in adhesion formation.

PMID- 9591504
TI  - Pathogenetic significance of increased levels of interleukin-8 in the peritoneal
      fluid of patients with endometriosis.
AB  - OBJECTIVE: To investigate the role of interleukin-8 (IL-8) in peritoneal fluid of
      patients with endometriosis in the pathogenesis of endometriosis. DESIGN:
      Peritoneal fluid was collected by laparoscopy. Endometrial and endometriotic
      stromal cells were obtained from normal endometrium and from chocolate cyst
      linings of the ovary. SETTING: Department of Obstetrics and Gynecology of Tottori
      University Hospital, Yonago, Japan. PATIENT(S): Forty women who underwent either
      laparoscopy or laparoscopic surgery. MAIN OUTCOME MEASURE(S): The peritoneal
      fluid concentration of IL-8 was analyzed by enzyme-linked immunosorbent assay,
      and the correlation between the IL-8 concentration and the extent of active
      endometriosis was investigated. The effect of IL-8 on cell proliferation was
      examined by tetrazolium bromide and thymidine incorporation. The expression of IL
      8 receptor was examined in stromal cells by reverse transcription polymerase
      chain reaction. RESULT(S): The level of IL-8 in peritoneal fluid was
      significantly higher in patients with endometriosis than in patients without
      endometriosis. A significant correlation was noted with the extent of active
      endometriosis. Interleukin-8 significantly increased the number of cells and DNA
      synthesis in the endometrial and endometriotic stromal cells in a dose-dependent
      manner. Transcripts of IL-8 receptor type A were detected in stromal cells.
      CONCLUSION(S): The present study suggests that IL-8 found in the peritoneal fluid
      of patients with endometriosis contributes to the pathogenesis of endometriosis.

PMID- 9591506
TI  - Chronic antiprogestin therapy produces a stable atrophic endometrium with
      decreased fibroblast growth factor: a 1-year primate study on contraception and
      amenorrhea.
AB  - OBJECTIVE: To describe the efficacy of mifepristone in the prevention of
      menstrual bleeding and ovulation, with similar observations in comparison groups.
      DESIGN: Prospective experimental study. Thirty-two cynomolgus monkeys were
      divided equally into four treatment groups (n = 8). Treatment lasted for 1 year.
      INTERVENTION(S): Group I received GnRH-agonist (GnRH-a) and in-sequence
      mifepristone, group II received mifepristone only, group III received GnRH-a
      only, and group IV received vehicle control. MAIN OUTCOME MEASURE(S): Serum
      estradiol and progesterone, menstrual bleeding, endometrial thickness, and
      endometrial expression of basic fibroblast growth factor (bFGF) as determined by
      immunohistochemistry. RESULT(S): Weekly progesterone determinations showed that
      mifepristone-treated monkeys seldom ovulated (6 ovulations in 8 years), compared
      with the controls (100 ovulations in 8 years), while maintaining early to
      midfollicular levels of circulating serum estradiol. The GnRH-a-only group also
      rarely ovulated, but was chronically and severely hypoestrogenic. The
      mifepristone-only group showed scant menstrual bleeding (5 days in 8 years) as
      compared with the menstrual frequency in control animals (422 days in 8 years).
      Endometrial proliferation, as determined by biopsy, was similarly minimal for
      both the GnRH-a and mifepristone groups, and statistically less than in control
      monkeys. Both the mifepristone and GnRH-a treatments suppressed endometrial gland
      expression of the angiogenesis polypeptide bFGF. CONCLUSION(S): Chronic
      mifepristone induced anovulation along with virtual amenorrhea, which suggests
      the worth of this novel hormonal contraceptive.

PMID- 9591505
TI  - Ovarian fecundity in patients with endometriosis can be estimated by the
      incidence of apoptotic bodies.
AB  - OBJECTIVE: To investigate the incidence of apoptotic bodies in membrana granulosa
      in patients with endometriosis. DESIGN: Retrospective analysis. SETTING: Yamagata
      University Hospital. PATIENT(S): Fifty-eight normoovulatory women with
      endometriosis and 45 patients with male factor infertility underwent ovulation
      induction for IVF-ET with GnRH analogues and gonadotropins. INTERVENTION(S):
      Patients underwent follicle aspiration after the administration of hCG. MAIN
      OUTCOME MEASURE(S): Recovered granulosa cells (GCs) were examined by fluorescence
      microscopy, and the incidence of apoptotic bodies was tabulated. These data and
      the other parameters associated with IVF results were analyzed on the basis of
      both the revised American Fertility Society (AFS) classification of endometriosis
      and the existence of chocolate cysts. RESULT(S): The incidence of apoptotic
      bodies in membrana granulosa of patients with endometriosis was significantly
      higher than that of the control (male factor infertility) group and increased as
      the stage of the revised AFS classification advanced. The incidence of apoptotic
      bodies in membrana granulosa was significantly higher in patients with chocolate
      cysts than in those without chocolate cysts. The patients with endometriosis had
      smaller numbers of developed follicles (> or = 15 mm), harvested oocytes, and
      mature oocytes than the male factor infertility patients. The existence of
      chocolate cysts corresponded with a reduced number of both harvested oocytes and
      mature oocytes. CONCLUSION(S): Through the apoptosis of GCs, the existence of
      endometriosis may have negatively affected the follicle development and oocyte
      quality.

PMID- 9591507
TI  - Alterations of the cytoskeleton and polyploidy induced by cryopreservation of
      metaphase II mouse oocytes.
AB  - OBJECTIVE: To determine cryopreservation-induced alterations in the cytoskeleton
      of metaphase II mouse oocytes and the implications of these alterations in
      functionality of the cytoskeleton and polyploidy after fertilization. DESIGN:
      Comparative study. SETTING: Clinical and academic research environment at a
      medical school teaching hospital. INTERVENTION(S): Oocytes were frozen using a
      slow-cooling (0.5 degrees C/min) and slow-thawing (8 degrees C/min) protocol in
      1.5 M dimethyl sulfoxide and 0.2 M sucrose and were analyzed before and after
      fertilization. MAIN OUTCOME MEASURE(S): Cytoskeletal alterations, fertilization,
      and polyploidy rates. RESULT(S): When analyzed immediately after thawing, the
      oocytes displayed dramatic cytoskeletal alterations. Only slight recovery was
      observed upon removal of the cryoprotectants. However, incubation after thawing
      of 1 hour at 37 degrees C completely reestablished a normal microfilament and
      microtubule pattern while partially restoring normal spindle morphology and
      chromosome alignment. Accordingly, insemination immediately after removal of
      cryoprotectants resulted in a significantly decreased fertilization rate and
      aberrant dynamics of cytoskeleton-dependent events, whereas oocytes inseminated
      after the post-thaw incubation displayed fertilization rates and cytoskeletal
      dynamics comparable to those in controls. Cryopreservation did not increase
      polyspermy but significantly increased digyny when the oocytes were inseminated
      after the post-thaw incubation. All digynic eggs displayed an abnormal spindle
      remnant in comparison with diploid or polyspermic eggs. CONCLUSION(S): A brief
      period of incubation after thawing allows recovery and positively affects
      fertilization and cytoskeletal dynamics. Cryopreservation does not impair the
      functionality of microfilaments and cytoplasmic microtubules during
      postfertilization events. Our findings suggest that the increased rate of digyny
      in cryopreserved oocytes may be related to the spindle disorganization, leading
      to failure in segregation of the chromosomes, rather than to direct malfunction
      of the microfilaments in polar body formation.

PMID- 9591508
TI  - Sex steroid hormones modulate serum ionized magnesium and calcium levels
      throughout the menstrual cycle in women.
AB  - OBJECTIVE: To determine the serum concentrations of the sex steroid hormones with
      respect to the concentrations of the biologically active fractions of magnesium
      and calcium during the different phases of the menstrual cycle. DESIGN:
      Controlled clinical study. SETTING: An academic research environment. PATIENT(S):
      Six parous and four nulliparous healthy cycling female volunteers. MAIN OUTCOME
      MEASURE(S): Concentrations of the sex steroid hormones estrogen, progesterone,
      and testosterone as well as the ionized Ca and Mg levels were measured in the
      serum of normal cycling women during five different stages: the menstrual, early
      follicular, late follicular, ovulatory (ovulatory/early luteal), and luteal
      phases. RESULT(S): In each woman, there was a comparatively high ionized Mg level
      coincident with the early follicular phase, a statistically significant decrease
      in ionized Mg around the time of ovulation, a significant decrease in ionized and
      total Mg when the serum progesterone concentration peaked, and a significant
      increase in the serum Ca2+/Mg2+ ratio at both the ovulatory and luteal phases. In
      addition, a decrease in ionized Mg was found with increased testosterone levels.
      CONCLUSION(S): Healthy women of reproductive age demonstrate recurring cycling of
      ionized Mg and cyclic alterations in the ionized Ca to Mg ratio in their serum.
      The changes in serum concentrations of these important physiologically active
      cations, in the range at which they occur, can affect such entities as the
      vasculature, synaptic transmission, and excitation-secretion coupling and thus
      can produce the well-known premenstrual syndromes during the luteal phase in
      women who are somewhat deficient in Mg or in those who have an unusually
      increased Ca2+/Mg2+ ratio.

PMID- 9591509
TI  - Estradiol and progesterone regulate the proliferation of human breast epithelial
      cells.
AB  - OBJECTIVE: To study the effects of estradiol and progesterone on the
      proliferation of normal human breast epithelial cells in vivo. DESIGN: Double
      blind randomized study. SETTING: Departments of gynecology and of cell biology at
      a university hospital. PATIENT(S): Forty postmenopausal women with untreated
      menopause and documented plasma FSH levels of >30 mIU/mL and estradiol levels of
      <20 pg/mL. INTERVENTION(S): Daily topical application to both breasts of a gel
      containing a placebo, estradiol, progesterone, or a combination of estradiol and
      progesterone during the 14 days preceding esthetic breast surgery or excision of
      a benign lesion. MAIN OUTCOME MEASURE(S): Plasma and breast tissue concentrations
      of estradiol and progesterone. Epithelial cell cycles were evaluated in normal
      breast tissue by counting mitoses and performing quantitative proliferating cell
      nuclear antigen immunolabeling analyses. RESULT(S): Increasing the estradiol
      concentration enhanced the number of cycling epithelial cells, whereas increasing
      the progesterone concentration significantly limited the number of cycling
      epithelial cells. CONCLUSION(S): Exposure to progesterone for 14 days reduced the
      estradiol-induced proliferation of normal breast epithelial cells in vivo.

PMID- 9591510
TI  - Culturing human embryos with and without glucose.
AB  - OBJECTIVE: To review published data and to compare pregnancy rates (PRs) after
      culturing human embryos with and without glucose and phosphate. DESIGN:
      Comparison of results from various programs. SETTING: Assisted Reproductive
      Technology Program. PATIENT(S): Patients were enrolled in various studies.
      INTERVENTION(S): Human embryos were cultured with and without glucose and
      phosphate. MAIN OUTCOME MEASURE(S): Pregnancy rates after different techniques of
      embryo culture. RESULT(S): Some studies reported higher PRs in patients
      undergoing IVF after embryos were cultured in media without glucose and phosphate
      versus media with glucose and phosphate. One study showed that PRs were lower
      when embryos were cultured in media lacking glucose and phosphate compared with
      media containing glucose and phosphate. Some studies have also shown similar PRs
      with the two types of culture media. CONCLUSION(S): The PRs in IVF patients will
      not necessarily be enhanced if the embryos are cultured in media without glucose
      and phosphate.

PMID- 9591511
TI  - Bladder endometriosis: deep infiltrating endometriosis or adenomyosis?
AB  - OBJECTIVE: To describe the anatomopathologic characteristics of endometriosis
      infiltrating the bladder detrusor. DESIGN: Descriptive anatomopathologic study.
      SETTING: Tertiary care center for endometriosis. PATIENT(S): Four patients, aged
      22-38 years, who underwent laparotomy for bladder endometriosis. INTERVENTION(S):
      Surgical excision and pathologic analysis of bladder endometriotic nodules in
      four patients. MAIN OUTCOME MEASURE(S): Gross and microscopic characteristics of
      endometriotic nodules. RESULT(S): A nodule of adenomyosis on the anterior wall of
      the uterus, in continuity with the detrusor lesion, was excised in three
      patients. In the other patient, bladder endometriosis was continuous with a
      nodule that infiltrated the left parametrium and extended as far as the posterior
      leaf of the ipsilateral broad ligament. Microscopically, all of the lesions had a
      similar histologic pattern: foci of endometriosis scattered in the bladder wall.
      The main feature was the paucity of endometrial-type stroma, particularly in the
      bladder submucosa, where glands were almost always dilated and cystlike and were
      lined by flattened cells. CONCLUSION(S): Analysis of our patients, although it
      does not pinpoint the pathogenesis of the disease, seems to exclude the
      hypothesized intraperitoneal origin of endometriotic lesions of the bladder
      detrusor.

PMID- 9591513
TI  - Appropriate scoring of testicular biopsies.

PMID- 9591512
TI  - Safe age for pregnancy?

PMID- 9591514
TI  - Predictive value of serum progesterone levels.

PMID- 9591515
TI  - Tolcapone: COMT inhibition for the treatment of Parkinson's disease.

PMID- 9591516
TI  - COMT inhibition: a new treatment strategy for Parkinson's disease.
AB  - During the initial stages of Parkinson's disease, treatment with levodopa plus a
      decarboxylase inhibitor (carbidopa or benserazide) provides adequate control of
      symptoms. However, as the disease progresses, the clinical response to treatment
      often begins to fluctuate, becoming increasingly correlated with fluctuations in
      plasma concentrations of levodopa-the "wearing-off" phenomenon. Many strategies
      have attempted, with various degrees of success, to increase the availability of
      levodopa and its active metabolites, thus reducing these fluctuations in
      response. This review focuses on the role of the new catechol O-methyltransferase
      (COMT) inhibitors tolcapone and entacapone as adjuncts to levodopa therapy. These
      agents act effectively and safely to increase the amount of levodopa that is
      available to enter the brain by extending the half-life of levodopa, resulting in
      more stable levels in the plasma and prolonging "on" time.

PMID- 9591517
TI  - Highlights of the North American and European experiences.
AB  - Two large, randomized, double-blind, placebo-controlled multicenter studies, one
      North American and one European, examined the efficacy and safety of 300 and 600
      mg/day tolcapone in similar populations of patients (n = 379) with Parkinson's
      disease currently taking levodopa and experiencing motor fluctuations. Change in
      "on-off" function was the most important end-point assessment. The two studies
      found similar results. The percentage of "on" time improved significantly and
      "off" time was reduced. Daily levodopa dosage requirements decreased
      significantly. The most common and significant adverse event was increased
      dyskinesia; hallucinations were not frequently encountered.

PMID- 9591518
TI  - Levodopa therapy: consequences of the nonphysiologic replacement of dopamine.
AB  - Normal motor function is dependent on the highly regulated synthesis and release
      of the transmitter dopamine by neurons projecting from the substantia nigra to
      the corpus striatum. Parkinson's disease involves the progressive degeneration of
      these neurons. Its core symptoms are a direct consequence of a striatal
      insufficiency of intrasynaptic dopamine. Levodopa, the standard of care for the
      treatment of PD, acts after its conversion to dopamine by restoring striatal
      dopaminergic transmission. However, there are significant differences between the
      normally functioning dopamine system and the restoration of function provided by
      standard levodopa treatment. Increasing clinical and preclinical evidence
      suggests that the intermittent stimulation of dopamine receptors resulting from
      current therapeutic regimens contributes to the response complications that
      ultimately affect most parkinsonian patients. It now appears that chronic
      nonphysiologic stimulation of dopaminergic receptors on striatal GABAergic
      neurons activates characteristic signaling pathways, leading to a potentiation of
      the synaptic efficacy of adjacent glutamatergic receptors of the N-methyl-D
      aspartate (NMDA) subtype. As a result, function of these GABAergic efferent
      neurons changes in ways that favor the appearance of motor complications.
      Conceivably, use of dopaminomimetic replacement strategies that provide more
      continuous dopamine receptor stimulation will act to prevent or alleviate these
      disabling complications. A number of promising approaches to achieving this goal
      are now under development.

PMID- 9591519
TI  - Influence of COMT inhibition on levodopa pharmacology and therapy.
AB  - Catechol O-methyltransferase (COMT) is an important enzyme that is linked
      directly to therapy with levodopa. Considering the demonstrated mechanism of
      action and pharmacologic profiles of COMT inhibitors, it is reasonable to
      hypothesize that these agents would improve the disability associated with
      Parkinson's disease. Two basic classes of COMT inhibitors are being studied in
      patients with PD: those that act exclusively extracerebrally or peripherally
      (e.g., entacapone) and those that cross the blood-brain barrier (e.g.,
      tolcapone). With COMT inhibition, greater peripheral bioavailability of levodopa
      occurs in humans without an enhancement of peak plasma levels. It is reasonable
      to suggest that COMT inhibition will be associated with prolonged effects of
      levodopa in PD, without increased peak dose toxicity in the form of dyskinesias
      and hallucinations.

PMID- 9591520
TI  - Pharmacokinetics, pharmacodynamics, and tolerability of tolcapone: a review of
      early studies in volunteers.
AB  - Tolcapone is a potent, reversible inhibitor of catechol O-methyltransferase
      (COMT) intended for use as an adjunct to levodopa therapy for Parkinson's disease
      (PD). Findings from the first pharmacokinetics/pharmacodynamics and tolerability
      studies of tolcapone in volunteers are reviewed. Following linear and dose
      proportional pharmacokinetics, tolcapone is rapidly absorbed and eliminated after
      single- or multiple-dose (i.e., tid) administration. Onset of COMT inhibition is
      rapid, substantial, and reversible, and is not affected by the co-administration
      of levodopa/decarboxylase inhibitor (levodopa/DCI). When given together with
      levodopa/DCI, tolcapone increases the relative bioavailability and plasma
      elimination half-life of levodopa, without affecting its peak plasma
      concentration. This leads to more stable plasma levels of levodopa, and the
      formation of 3-O-methyldopa is effectively reduced. Tolcapone was well tolerated
      alone or in combination with levodopa/DCI, and the results indicated that the
      effective dose in patients with PD would be in the range of 50-400 mg tid.

PMID- 9591521
TI  - Tolcapone in stable Parkinson's disease: efficacy and safety of long-term
      treatment. Tolcapone Stable Study Group.
AB  - In this double-blind, placebo-controlled trial, we investigated the effect of the
      catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily
      on activities of daily living and motor function in 298 patients with
      parkinsonism receiving levodopa but without motor fluctuations. At 6 months, both
      dosages of tolcapone produced significant reductions in the Unified Parkinson's
      Disease Rating Scale scores for activities of daily living (Subscale II) and
      motor function (Subscale III) and in the total score for Subscales I to III.
      These improvements were maintained up to the 12-month assessment. At 6 months,
      both tolcapone groups had changes in levodopa dosage that were significantly
      different from placebo: the tolcapone groups had decreases in mean total daily
      dose of levodopa, whereas the placebo group had a mean increase. Tolcapone was
      well tolerated. The principal adverse events were levodopa-related, but these
      were generally mild or moderate. Diarrhea was the most frequent nondopaminergic
      adverse event. Tolcapone appears to be beneficial in the treatment of patients
      with parkinsonism who have not yet developed motor fluctuations.

PMID- 9591522
TI  - Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off"
      phenomenon and levodopa requirements in fluctuating parkinsonian patients.
AB  - BACKGROUND: More than 50% of patients with Parkinson's disease develop motor
      response fluctuations (the 'wearing off" phenomenon) after more than five years
      of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has
      been shown to increase levodopa bioavailability and plasma elimination half life,
      thereby prolonging the efficacy of levodopa. OBJECTIVES: The primary objective
      was to evaluate the efficacy of tolcapone in reducing "wearing off" in levodopa
      treated, fluctuating parkinsonian patients. Secondary objectives included
      assessment of reduction in levodopa requirements, improvement in patients'
      clinical status, duration of improvements, and tolerability of tolcapone.
      METHODS: In this multicentre, randomised, double blind, placebo controlled trial,
      58 patients received placebo, 60 received 100 mg tolcapone three times daily
      (tid), and 59 received 200 mg tolcapone tid, in addition to levodopa/benserazide.
      RESULTS: After three months with 200 mg tolcapone tid, "off" time decreased by
      26.2% of the baseline value, "on" time increased by 20.6% (p < 0.01 vs. placebo),
      and the mean total daily levodopa dose decreased by 122 mg from the baseline dose
      of 676 mg (p < 0.01). These responses were maintained up to nine months. With 100
      mg tolcapone tid, "off" time decreased by 31.5% (p < 0.05), "on" time increased
      by 21.3% (p < 0.01), and the mean total daily levodopa dose decreased by 109 mg
      from the baseline dose of 668 mg (p < 0.05). With 200 mg tolcapone tid, unified
      Parkinson's disease rating scale motor and total scores were significantly
      reduced, and quality of life (sickness impact profile) scores were significantly
      improved. Both dosages were well tolerated. Dyskinesia was the most often
      reported levodopa induced adverse event. Diarrhoea was the most often reported
      non-dopaminergic adverse event and the most frequent reason for withdrawal from
      the study: four patients in the 100 mg tolcapone tid group and six in the 200 mg
      tid group withdrew because of diarrhoea. CONCLUSION: Tolcapone prolongs "on" time
      in fluctuating parkinsonian patients while allowing a reduction in daily levodopa
      dosage, thereby improving the efficacy of long term levodopa therapy.

PMID- 9591523
TI  - Tolcapone improves motor function in parkinsonian patients with the "wearing-off"
      phenomenon: a double-blind, placebo-controlled, multicenter trial.
AB  - We studied the new catechol-O-methyltransferase inhibitor tolcapone, 100 and 200
      mg, three times daily (tid) in a randomized, double-blind, parallel-group trial
      involving 202 parkinsonian patients who were experiencing the "wearing-off"
      phenomenon on levodopa therapy. After 3 months, patients receiving tolcapone had
      a significant decrease in mean daily levodopa dose requirement compared with
      placebo-treated patients (p < 0.01). In patients treated with tolcapone 200 mg
      tid, daily "off" time, measured using patient diaries, was reduced from baseline
      by 3.25 hours; this reduction was significantly different from that seen in the
      placebo group (p < 0.01). Moreover, the number of daily levodopa intakes was
      reduced significantly in each tolcapone group compared with placebo (p < 0.01).
      We found significant improvements in motor function and overall efficacy in the
      tolcapone groups (p < 0.01). The most frequent adverse events were associated
      with levodopa treatment. Dyskinesia developed or worsened in 18% of patients
      receiving placebo, in 51% receiving tolcapone 100 mg tid, and in 64% receiving
      200 mg tid, with most cases occurring within the first 30 days of the study.
      Diarrhea was the most frequent nondopaminergic event, occurring in 14% on
      placebo, 13% on tolcapone 100 mg tid, and 19% on 200 mg tid. Overall 18% of
      patients withdrew because of adverse events: 15% on placebo, 17% on tolcapone 100
      mg tid, and 22% on 200 mg tid. We conclude that tolcapone as an adjunct offers
      promise for the relief of the "wearing-off " phenomenon in levodopa-treated
      parkinsonian patients.

PMID- 9591524
TI  - Relationship between free-living daily physical activity and ambulatory measures
      in older claudicants.
AB  - The purpose of this study was to determine the relationship between free-living
      daily physical activity and ambulatory measurements in peripheral arterial
      occlusive disease (PAOD) patients with intermittent claudication. Thirty-four
      older, nonsmoking PAOD patients with intermittent claudication (age=69.0 +/- 6.0
      years, ankle/brachial index [ABI] =0.63 +/- 0.18) were recruited from the
      Vascular Clinic at the Baltimore Veterans Affairs Medical Center and from radio
      and newspaper advertisements. Energy expenditure of physical activity (EEPA) was
      determined by using doubly labeled water and indirect calorimetry techniques.
      Patients were also characterized on claudication distances and peak oxygen uptake
      during a graded treadmill test, 6-minute walking distance, weight, body mass
      index, and percent body fat. The claudication patients were sedentary, as EEPA
      was 362 +/- 266 kcal/day. EEPA was related to the 6-minute walk distance (369 +/-
      68 meters; r=0.629, P<0.001), to the number of steps taken during 6 minutes (605
      +/- 99 steps; r=0.485, P=0.008), to the treadmill distance to maximal
      claudication (313 +/- 131 meters; r=0.470, P=0.010), and to the time to relief of
      pain (6:21 +/- 3:57 min:sec; r=-0.417, P=0.017). None of the other ambulatory and
      body composition measurements were correlated with EEPA. In conclusion, a
      reduction in free-living daily physical activity was associated with a decrease
      in ambulatory ability and with more severe intermittent claudication in older
      PAOD patients.

PMID- 9591525
TI  - Perspectives in the treatment of dyslipidemias in the prevention of coronary
      heart disease.
AB  - In this review the indications for the available treatments for dyslipidemias in
      the prevention of coronary heart disease (CHD) are considered, and their efficacy
      according to the latest studies is analyzed. As data sources the authors used the
      main multicenter studies performed in the last twenty years to evaluate primary
      and secondary prevention of CHD by correcting dyslipidemias as well as the
      results of meta-analyses of these studies. All treatments considered were found
      effective in preventing CHD morbidity and mortality to some extent. In
      particular, the combination of diet with niacin or hydroxymethylglutaryl coenzyme
      A (HMG CoA) reductase inhibitors seems to give the best results. These drugs
      induce a marked reduction of total and low-density lipoprotein (LDL) cholesterol
      and an increase of high-density lipoprotein (HDL) cholesterol concentrations. The
      use of diet, niacin, and HMG CoA reductase inhibitors reduces total as well as
      specific mortality. Treatment of dyslipidemia to prevent CHD depends on the
      pattern and severity of dyslipidemia, the presence of overt CHD, and the
      patient's response to diet. Pharmacologic treatment should be started only after
      dietary modifications have been tried and must be combined with diet. Drug side
      effects must also be considered, for they may affect patient compliance. High
      levels of total and LDL and low levels of HDL cholesterol are major risk factors
      for coronary atherosclerosis. Correcting lipid abnormalities can reduce the risk
      of development or progression of CHD. Diet and drugs are the main instruments
      available to normalize lipid levels. The choice of drug to combine with diet must
      be based on its specific effects on lipid metabolism, side effects, and efficacy
      in reducing CHD.

PMID- 9591526
TI  - Clinical characteristics and follow-up of patients with chest pain and normal
      coronary arteries.
AB  - The authors identified 160 men and women from all 3,700 patients with anginal
      pain between 1990 and 1994 who were subsequently found to have normal coronary
      arteries at diagnostic cardiac catheterization with follow-up to the present
      (mean follow-up 2.5 years). The group comprised 50 women and 110 men. Mean age
      was significantly greater in women (53.1 +/- 7.7 vs 47.2 +/- 9.2 years, p<0.001).
      Forty percent of the women but only 10% of the men had a positive exercise test.
      At follow-up, a larger proportion of patients continue to experience chest pain
      (95 patients, 59%) of whom 65 patients (41%) continue antianginal therapy.
      Furthermore one patient suffered a sudden cardiac death and two patients had a
      nonfatal myocardial infarction. Of patients referred with chest pain, women were
      more likely to have normal coronary arteries, compared with men. All patients
      have an excellent prognosis. A large proportion of women had a positive exercise
      test in the absence of coronary artery disease. On the other hand, morbidity
      remains high in these patients, despite the reassurance of a normal-appearing
      coronary arteriogram.

PMID- 9591527
TI  - Congenital isolated apical ventricular septal defects.
AB  - The diagnosis of apical ventricular septal defects (VSDs) is difficult and the
      ratio of spontaneous closure is not well known. At the Ankara University
      Pediatric Cardiology Department, between the years 1992 and 1997, 33 patients
      were identified by color-flow Doppler (CFD) imaging as having a small defect at
      the apical portion of the ventricular septum. The age range was 1 day to 13
      years. All patients were asymptomatic with normal telecardiograms and
      electrocardiograms. There were grade 2-3/6, pansystolic murmurs at the apex or
      closer to the apex in 19 patients. In 30 patients, narrow and short colored jets
      were seen at the apex of the heart, distal to the moderator band. The jets were
      wide in three patients. These defects were difficult to image and required
      specific angulation of the transducer. Of the 23 patients who had follow-up
      examinations, at 3 months to 3.5 years, there was spontaneous closure in ten
      (43.5%). To the authors' knowledge, this report is the largest series of isolated
      apical trabecular ventricular septal defects (t-VSDs). In their experience, color
      flow imaging is more sensitive in detecting a small apical VSD. They conclude
      that although the closure of apical VSD is not the rule, the prognosis is
      excellent.

PMID- 9591529
TI  - Effect of felodipine on arterial blood flow and venous function at rest in
      patients with mild essential hypertension.
AB  - Felodipine is a second-generation dihydropyridine calcium antagonist used to
      treat mild to moderate arterial hypertension. The authors used venous occlusion
      plethysmography to study the effect of this drug on lower limb arterial inflow
      and venous outflow in 10 at rest patients with mild essential hypertension. They
      also sought correlations between changes in district blood flow and blood
      pressure. Plethysmography was carried out at 8 AM and 4, 8, and 24 hours later at
      baseline (after washout), on the first day of treatment with a single daily
      administration of 10 mg felodipine ER, and after 7 and 30 days of treatment. The
      drug was given after the 8 AM evaluation. The authors determined rest flow,
      maximal venous incremental volume (MVIV) at 40 mmHg and 60 mmHg, and gradient of
      venous volume between 60 and 40 mmHg divided by the pressure difference (DV/DP)
      as index of venous distensibility. On the days of plethysmographic evaluation,
      arterial blood pressure and heart rate were measured continuously over 24 hours
      by the ABPM (Ambulatory Blood Pressure Monitoring). The results were analyzed by
      ANOVA. Rest flow, MVIV, and DV/DP were stable at the baseline evaluation. On days
      1, 7, and 30 of treatment the rest flow after 4 and 8 hours was significantly
      greater than at 8 AM but had always returned to normal after 24 hours. No other
      plethysmographic parameters changed significantly; in particular venous outflow
      remained unchanged. Mean arterial, systolic, and diastolic blood pressure were
      significantly reduced, compared with baseline, following treatment on the first
      day and after 7 and 30 days' treatment. There was no effect on heart rate. The
      authors conclude that felodipine is useful for the treatment of mild essential
      hypertension, since it reduces arterial resistance without altering venous
      capacitance or distensibility.

PMID- 9591528
TI  - Tortuosity, kinking, and coiling of the carotid artery: expression of
      atherosclerosis or aging?
AB  - The etiology of carotid abnormalities is both congenital than acquired. The aim
      of this study was to clarify the role of aging and atherosclerosis in the
      acquired cases, and the role of these abnormalities in hemodynamic alterations
      and neurologic symptoms. Over a 1-year period the authors studied all the
      subjects undergoing carotid examination by continuous-wave and color-coded
      Doppler sonography at an Angiology Unit. They evaluated neurologic symptoms; risk
      factors for atherosclerosis; number, sites, and kinds of carotid abnormalities;
      atherosclerotic lesions; stenosis; hemodynamic alterations of the carotid; and
      other localizations of atherosclerotic diseases. There were 469 subjects: 272
      (58%) with abnormalities (group 1) and 197 (42%) without abnormalities (group 2).
      The total number of abnormalities was 479 (104 tortuosities, 262 kinkings, and
      113 coilings). The abnormalities were more prevalent in the elderly (P<0.001) and
      in women (P<0.001). In group 1 they found significant prevalences of hyperlipemia
      (P<0.001), hypertension (P<0.01), chronic cigarette smoking (P<0.01), and
      ischemic heart disease (P<0.05). Carotid atherosclerotic lesions were more
      prevalent in group 1 than in group 2 (P<0.001); among the patients with
      atherosclerotic carotid lesions, those in group 1 were older than those in group
      2 (P<0.001). Tortuosity seemed to be associated with fewer hemodynamic
      alterations. The authors conclude that atherosclerosis, hypertension, and aging
      may play an important role in producing carotid abnormalities. The aging seemed
      more important than atherosclerosis. Only a prospective study of patients with
      carotid abnormalities and no atherosclerotic lesion will clarify the role of
      hemodynamics and neurologic symptomatology.

PMID- 9591530
TI  - Basic fibroblast growth factor increased regional myocardial blood flow and
      limited infarct size of acutely infarcted myocardium in dogs.
AB  - Basic fibroblast growth factor (bFGF), a growth factor potent in promoting
      angiogenesis, has been shown to reduce infarct size in experimentally induced
      acute myocardial infarction. However, the effect of bFGF on regional myocardial
      blood flow (Qm) in the acutely infarcted myocardium has not been well clarified.
      In 20 open-chest dogs, the left anterior descending (LAD) coronary artery was
      occluded and animals were maintained in this condition for 4 weeks. In eight of
      these dogs, bFGF (300 microg) was injected into the myocardium supplied by the
      LAD and the artery was ligated (bFGF group), and in the other 12 dogs, saline was
      injected (control group). Nonradioactive colored microspheres were used to
      measure Qm. The amount of viable myocardium as percent of visual field in the
      microscope and the extent of fibrosis scored histologically from 0 to 5 in the
      infarcted area 4 weeks after occlusion were measured. In the outer layer, the Qm
      values immediately after and 4 weeks after occlusion were 26 +/- 2% and 70 +/-
      6%, respectively, in the control group, and 46 +/- 5% and 121 +/- 13%,
      respectively, in the bFGF group. The Qm at both times in the bFGF group was
      significantly higher than the corresponding control group values (p < 0.01). The
      Qm at 4 weeks in the inner and the middle layers also significantly increased in
      the bFGF group. There was more viable myocardium (control vs bFGF group; 41 +/- 5
      vs 61 +/- 7%, p < 0.05) and less fibrosis (3.1 +/- 0.2 vs 2.0 +/- 0.4, p < 0.01)
      at the outer layer in the bFGF group. It was found that bFGF caused a marked
      increase in Qm, an increase of viable myocardium, and a decrease of fibrosis in
      the infarcted myocardium in dogs.

PMID- 9591531
TI  - Immunolabeling of type IV collagen, laminin, and alpha-smooth muscle actin cells
      in the intima of normal and varicose saphenous veins.
AB  - Smooth muscle cells (SMC) of normal and varicose human saphenous intima were
      studied on cryostat sections by immunohistochemistry with alpha-smooth muscle
      actin (ASMA), type IV collagen, and laminin antibodies and also by transmission
      electron microscopy. The findings suggest two structurally distinct subtypes of
      smooth muscle cells with thin and thicker external lamina. Thin external lamina
      SMC were characterized by laminin, type IV collagen, weaker external lamina
      reactivity, and intense cytoplasmic alpha-smooth muscle actin immunoreactivity.
      Ultrastructurally, they exhibited abundant cytoplasmic microfilaments and thin
      external lamina. These cells were found isolated or, more frequently, clustered
      in fascicles close to the subendothelium in focal or zonal cushions, or in
      diffuse enlargement of the intima. In contrast, thicker external lamina smooth
      muscle cells were intensely immunolabeled for laminin and collagen IV, showing
      irregular cytoplasmic ASMA reaction. Single or clustered thicker external lamina
      SMC were seen predominantly in zonal cushions and in intima diffuse enlargement.
      It is very likely that these cells secrete these matrices in a nonpolarized
      fashion. The thicker external lamina of these SMCs showed a fine granular
      amorphous aspect sometimes intermingled with microfibrils. These external lamina
      were interposed between neighboring cells and exposed to collagen fibrils and
      elastic fibers. The cells also exhibited rarefaction of the cytoplasmic
      filaments. Intermediary cells exhibiting both features were rarely seen. Thicker
      external lamina SMC should be discussed in the context of an
      adaptive/proliferative response leading to dysfunction of the fibroelastic
      properties of the vein wall.

PMID- 9591532
TI  - Combined protein C deficiency and protein C activated resistance as a cause of
      caval, peripheral, and cerebral venous thrombosis--a case report.
AB  - A 26-year-old woman suffered concomitant inferior vena cava, iliac, and femoral
      vein thrombosis and cerebral venous thrombosis. Ten days before symptom onset she
      had started using an oral contraceptive that contained low-dose ethynilestradiol
      and gestodene. Both protein C deficiency and protein C activated resistance were
      detected. To our knowledge, the association of cerebral, caval, and ilio-femoral
      popliteal venous thrombosis has not been described previously. The severity of
      the clinical features could be a consequence of the two combined thrombophilic
      mechanisms and of the continuation of the oral contraceptive. A thrombophilic
      disorder should be considered in young patients with thromboembolic disease.
      Because of the high prevalence of the genetic deficiency causing protein C
      activated resistance, it is probably worthwhile to perform general screening
      before prescription of oral contraceptives.

PMID- 9591534
TI  - Buerger's disease in two brothers: iliac artery occlusion by thromboangiitis
      obliterans--case reports.
AB  - Several characteristics of thromboangiitis obliterans are unique and confirm the
      existence of the disease as a distinct pathological entity. Its predilection for
      young smoking males, peripheral type of vascular involvement, recurrences of
      superficial thrombophlebites, and typical histolopathology form the principals of
      the disease although the etiology remains unknown. The authors report the unusual
      finding of Buerger's disease occurring in two brothers, one of whom had occlusion
      of the left external iliac and femoral arteries. All other clinical
      characteristics of these two cases were typical for thromboangiitis obliterans.
      Presentation of some peculiarities of the disease, particularly the lack of
      familial association, may help to unravel the pathogenesis of thromboangiitis
      obliterans.

PMID- 9591533
TI  - A case of rapidly progressive pulmonary aneurysm as a rare complication of
      Behcet's syndrome--a case report.
AB  - One of the severe complications of Behcet's syndrome is pulmonary arterial
      involvement. The authors report a patient with Behcet's syndrome who had the
      complications of multiple pulmonary arterial aneurysms presenting with hemoptysis
      and right ventricular thrombus. He underwent emergency surgery because of failure
      of intensive immunotherapy and died 2 months after the surgery.

PMID- 9591535
TI  - Late development of renal arteriovenous fistula following gunshot trauma--a case
      report.
AB  - A 43-year-old man presenting with symptoms of congestive heart failure,
      cardiomegaly, and impaired left ventricular (LV) function was diagnosed as having
      a huge left renal arteriovenous (AV) fistula. The AV fistula might be attributed
      to a gunshot wound suffered during his military service twenty years ago.
      Percutaneous transcatheter arterial embolization utilizing multiple spring coils
      in conjunction with cyanoacrylic glue successfully occluded the fistula, with
      subsequent improvement of LV function and reduction of LV size on his serial
      echocardiographic follow-up.

PMID- 9591536
TI  - Diagnostic value of the preoperative sestamibi scan in intraoperative
      localization of parathyroid adenomas: a case study.
AB  - A retrospective chart review of 43 patients who underwent technetium 99m (Tc-99m)
      sestamibi scans from June 1995 to January 1997 was performed. Only those who
      underwent subsequent parathyroid exploration with excision were included in the
      study. Twenty subjects (13 women and seven men) were included in the study. Ages
      ranged from 21 to 84 years (mean, 58 years). All patients had laboratory values
      and clinical findings consistent with primary hyperparathyroidism. Two patients
      had preoperative magnetic resonance imaging (MRI) scans (one patient with
      recurrent disease), and one had a preoperative computed tomography (CT) scan. The
      remaining patients had the sestamibi scan as the only preoperative localization
      study. There were 18 pathologic diagnoses of parathyroid adenoma and two of
      parathyroid hyperplasia. Sestamibi failed to correctly identify the location of
      the parathyroid lesion in two cases. In 18 cases the preoperative sestamibi scan
      correctly localized the lesion, a predictive value of 90%. We conclude that the
      Tc-99m sestamibi scan is an accurate preoperative tool that can be used as a
      single modality to localize parathyroid adenomas.

PMID- 9591537
TI  - Regulators of proliferation and apoptosis in carcinoma of the larynx.
AB  - Expression of interrelated gene products regulating cell proliferation and
      apoptosis may be disordered in squamous cell carcinoma (SCC) of the larynx
      compared with normal squamous mucosa. Certain of these abnormalities, alone or in
      combination, may be of prognostic significance in low-stage carcinomas of the
      larynx. A retrospective study of archival material was made. Expression of the
      Bcl-2 family of apoptosis-related genes (bcl-2, bcl-X, mcl-1, and bax) and the
      proliferation- and apoptosis-related genes p53 and cyclin D-1 were determined in
      40 low-T-stage laryngeal carcinomas and in uvular epithelium from patients
      without SCC. Among the antiapoptotic members of the Bcl-2 family, Bcl-X and Mcl-1
      showed more intense and widespread staining than Bcl-2 itself in both normal
      squamous mucosa and SCC. The well-ordered expression patterns of Bcl-2-related
      proteins found in normal epithelium were lost in SCC, and patterns of expression
      varied widely among individual tumors. Also, mean expression levels for Bax and
      cyclin D-1 were significantly lower than in normal epithelium (P = .036 and P =
      .009, respectively), whereas expression of p53 was higher in tumors (P = .034).
      Expression of Bcl-X and Mcl-1 was greater in poorly differentiated than in well
      differentiated tumors (P = .014 and P = .031, respectively). No associations were
      seen between marker expression patterns and clinical outcome in this group of
      patients. Bcl-x and Mcl-1 appear to be the most abundantly expressed
      antiapoptotic proteins of the Bcl-2 family in both normal squamous mucosa and SCC
      of the larynx. Multiple genes regulating proliferation and apoptosis are
      expressed abnormally in laryngeal SCC compared with normal epithelium. In
      particular, loss or measurable decrease in expression of the proapoptotic protein
      Bax in tumors may contribute to the deranged growth control of SCC. Further study
      is needed to evaluate the prognostic significance of particular patterns of
      disordered expression of proteins regulating proliferation and apoptosis in SCC
      of different head and neck sites.

PMID- 9591538
TI  - Differentially expressed genes in head and neck cancer.
AB  - Carcinogenesis is considered a multistep process. To further elucidate involved
      genetic changes, the differential display method was applied to compare gene
      expression of head and neck carcinoma cells and normal keratinocytes from the
      upper aerodigestive tract. Total RNA was extracted from cultured squamous
      carcinoma cells and keratinocytes. mRNA was reverse transcribed into cDNA,
      amplified by PCR, and separated on a gel. Currently three DNA transcripts were
      identified with a length of 191 to 336 base pairs (bp) that were either expressed
      only by the keratinocytes or by the malignant cells. Differentially expressed DNA
      fragments of the carcinoma cells and the keratinocytes were cloned and sequenced.
      A gene bank database search identified one fragment expressed by the carcinoma
      cells as an unknown gene, another one found in the keratinocytes as probably a
      part of the human cell attachment domain, and the third one with homology to the
      mRNA of the human epidermal growth factor receptor (EGFR). Northern blot analysis
      confirmed the differential expression in the malignant cells or the
      keratinocytes. Differential display seems to confirm the well-known
      overexpression and up-regulation of the EGFR, the differential expression of the
      cell attachment domain may play a role as a cofactor in carcinogenesis of head
      and neck cancer, and the third unknown fragment is still under investigation to
      elucidate the role in carcinogenesis.

PMID- 9591539
TI  - Repair of orbital blow-out fractures with nasoseptal cartilage.
AB  - The goals of reconstruction in orbital blow-out fractures are to restore floor
      continuity, provide support of orbital contents, and prevent fibrosis of soft
      tissues. Although ease of use has popularized alloplasts, autogenous material
      provides greater biocompatibility and results in low rates of infection,
      extrusion, and migration. Nasoseptal cartilage is an easily accessible, abundant,
      autogenous source that provides support to the orbital floor and minimal donor
      site morbidity. Thirteen patients who presented with orbital blow-out fractures
      underwent reconstruction with nasoseptal cartilage. Follow-up at 3 months to 4
      years shows one patient with persistent manifest enophthalmos requiring further
      augmentation. There were no recipient or donor site complications. Nasoseptal
      cartilage is an underutilized and superior material for reconstruction of orbital
      blow-out fractures.

PMID- 9591540
TI  - Immunohistochemical analysis of proliferating cells in a sterile labyrinthitis
      animal model.
AB  - Inflammatory reactions within the cochlea lead to the formation of fibrotic
      tissue and bone. To determine which cells are involved in the proliferation of
      the inflammatory response within the cochlea, sterile labyrinthitis was created
      by inoculating keyhole limpet hemocyanin (KLH) into the scala tympani of
      systemically sensitized animals. Cellular proliferation was assessed
      immunohistochemically using the monoclonal antibody Ki-67. Proliferating cells
      were identified among inflammatory cells and fibroblasts within the matrix, as
      well as in endosteal cells lining the scala tympani. Inflammatory and potential
      osteoprogenitor cells were labeled as late as 6 weeks after inoculation,
      suggesting the absence of a strong immunosuppressive mechanism. Endosteal cells
      may proliferate and secrete the extracellular matrix used by the inflammatory
      cells to move within the cochlear scalae. They may also participate in the
      ossification of the inflammatory matrix.

PMID- 9591541
TI  - Inlay tympanoplasty: cartilage butterfly technique.
AB  - For closure of a nonmarginal tympanic membrane perforation, currently popular
      techniques utilize either an underlay or an onlay approach. However, both
      procedures require incising canal skin. A transcanal inlay procedure could
      provide theoretical advantages of ease, speed, and comfort. Specifically designed
      cartilage that could facilitate the transcanal approach similar to placement of a
      solid tube was employed and evaluated. A transcanal cartilage butterfly inlay
      technique was found to be efficient and effective to close a subgroup of small-to
      medium-sized tympanic membrane perforations including cases in which the
      condition of the tympanic membrane was somewhat hostile. Postoperative patient
      comfort was an additional benefit.

PMID- 9591542
TI  - Penetration of ceftazidime into middle ear fluid in children with otitis media
      with effusion.
AB  - Twenty-five children with otitis media with effusion received ceftazidime 50
      mg/kg intravenously before bilateral myringotomy with insertion of tympanostomy
      tubes. Concentrations of ceftazidime measured in serum and middle ear fluid
      exceeded 4 mg/L (i.e., largely above the minimal inhibitory concentrations for
      the gram-negative pathogens commonly recovered from children with otitis media)
      for at least 4 hours. Mean peak concentrations occurred 30 to 90 minutes after
      the injection and reached 11 to 14 mg/L. These results are in keeping with the
      clinical efficacy of ceftazidime in the treatment of chronic middle ear
      infections in children.

PMID- 9591543
TI  - Childhood imbalance and chronic otitis media with effusion: effect of
      tympanostomy tube insertion on standardized tests of balance and locomotion.
AB  - The goal of this study was to investigate the role of chronic otitis media with
      effusion as a cause of childhood imbalance. Nineteen 4- to 6-year-old children
      with chronic otitis media with effusion and 14 matched control children underwent
      a series of laboratory tests, including two standardized tests of balance and
      locomotion: the Peabody Developmental Motor Scales (PDMS) and the Bruininks
      Oseretsky Test of Motor Proficiency (BOTMP). The children in the chronic otitis
      media with effusion group underwent tympanostomy tube insertion. Both groups
      underwent the same battery of tests within 6 to 8 weeks of initial testing.
      Analysis of variance for the PDMS and BOTMP demonstrated significantly lower
      performance in the balance subscales for the otitis group before (P < .01). Both
      otitis and control groups improved when retested. The improvement was greater and
      approaching significance in the otitis group on the PDMS and BOTMP (P = .056 and
      .097, respectively). It is concluded that chronic otitis media with effusion
      significantly affects balance and coordination skills in 4- to 6-year-old
      children. These skills improve after tympanostomy tube insertion at a rate
      greater than that of the control group.

PMID- 9591544
TI  - Neurotrophin 3, not brain-derived neurotrophic factor or neurotrophin 4, knockout
      mice have delay in vestibular compensation after unilateral labyrinthectomy.
AB  - On the basis that neurotrophins (NTs) affect neuronal synaptic plasticity, are
      expressed in various cell types of the vestibular system, and exert a trophic
      influence on statoacoustic neurons, the authors hypothesized a role for NTs in
      vestibular compensation. To test this hypothesis, they performed unilateral
      surgical labyrinthectomy in 11 heterozygous (+/-) neurotrophin 3 (NT3) and brain
      derived neurotrophic factor (BDNF) knockout mice and in two neurotrophin 4 (NT4)
      homozygous (-/-) knockout mice, each with a control (+/+) sibling, for a total of
      26 mice. Four BDNF(+/-) and four NT3(+/-) mice with their (+/+) controls each
      were allowed to recover in a normal lighted room for 3, 7, 14, and 30 days
      following labyrinthectomy. Two BDNF(+/-) and two NT4(-/-) mice with controls were
      kept in total darkness for 1- and 16-day survival periods. One NT3(+/-) mouse
      without a control (which died in surgery) was sacrificed after 16 days in
      darkness. The behavior of all mice was videorecorded to monitor their recovery.
      Compared with normal (+/+) littermate controls, NT3(+/-) mice demonstrated a
      delay in compensation (8 to 10 days) in light surround, whereas NT4(-/-) mice
      showed only a minor delay in dark surround. Despite a 40% lower vestibular
      ganglion cell population in BDNF(+/-) mice compared with (+/+) controls, BDNF(+/
      ) mice did not reveal a detectable delay in recovery following labyrinthectomy.
      These findings suggest that a 50% loss of NT3 protein significantly affects
      vestibular recovery in adult mice. Perhaps variations in achieving vestibular
      compensation in humans may be partly secondary to genetically different NT3
      levels in vestibular pathways.

PMID- 9591545
TI  - The cerebellopontine angle: does the translabyrinthine approach give adequate
      access?
AB  - A long-standing but unfounded criticism of the translabyrinthine approach is the
      misperception that this approach does not give adequate access to the
      cerebellopontine angle. Because of what is perceived as limited visualization and
      operating space within the cerebellopontine angle, some surgeons still believe
      that the translabyrinthine approach is inappropriate for large acoustic tumors.
      In this study, the surgical access to the cerebellopontine angle by virtue of the
      translabyrinthine approach is measured and analyzed. The parameters are compared
      with those measured for the retrosigmoid approach. This series objectively
      confirms that the translabyrinthine approach offers the neurotologic surgeon a
      shorter operative depth to the tumor, via a similar-sized craniotomy. This
      permits superior visualization by virtue of a wider angle of surgical access.
      Such access is achieved with the merit of minimal cerebellar retraction.

PMID- 9591546
TI  - Influence of the gas exchange function through the middle ear mucosa on the
      development of sniff-induced middle ear diseases.
AB  - To investigate the influence of gas exchange function through the middle ear
      mucosa on the development of sniff-induced middle ear diseases, the authors
      examined the mastoid pneumatization among patients with sniffing habit using
      computed tomography, and also examined the change of negative middle ear pressure
      induced by sniffing using tympanogram. In 20 ears with cholesteatoma or adhesive
      otitis media, the areas of mastoid cavity measured at the level of the lateral
      semicircular canal were significantly smaller than those in 26 ears with otitis
      media with effusion (OME) or attic retraction and in eight normal ears with
      sniffing habit (P < .01 and P < .0001, respectively). In 26 ears with OME or
      attic retraction, the areas of mastoid cavity were significantly smaller than
      those in eight normal ears with sniffing habit (P < .0001). By contrast, in the
      four ears with sniff-induced middle ear disease, the recovery of negative middle
      ear pressure in 5 minutes without swallowing was less than 10 mm H2O, whereas in
      all seven ears with normal eardrum, negative middle ear pressure recovered by
      more than 20 mm H2O in 5 minutes. These findings suggested that impairment of gas
      exchange function through the middle ear mucosa, as well as eustachian tube
      dysfunction, might be closely related to the development of sniff-induced middle
      ear diseases.

PMID- 9591547
TI  - Effects of chronic electrical stimulation on spiral ganglion neuron survival and
      size in deafened kittens.
AB  - We have studied spiral ganglion cell (SGC) survival and soma size in neonatally
      pharmacologically deafened kittens. They were implanted with a four-electrode
      array in the left cochlea at 100 to 180 or more days of age. Eight animals were
      chronically stimulated approximately 1000 hours over approximately 60 days with
      charge-balanced, biphasic current pulses; three were unstimulated controls. Using
      three-dimensional computer-aided reconstruction of the cochlea, the SGC position
      and cross-sectional area were stored. SGC position was mapped to the organ of
      Corti by perpendicular projections, starting from the basal end. The basal region
      of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1
      mm of the length of the organ of Corti) and soma size for stimulated cochleae
      were compared statistically with implanted but unstimulated cochleae. There was
      no evidence of an effect of electrical stimulation on SGC survival under this
      protocol and with this duration. On the other hand, the cell size on the
      stimulated side was significantly larger than the control side in the middle
      segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after
      prolonged auditory deprivation; however, these changes may be partially moderated
      after chronic intracochlear electrical stimulation.

PMID- 9591548
TI  - Functional endoscopic sinus surgical outcomes for contact point headaches.
AB  - Headaches secondary to sinonasal anatomic abnormalities continue to remain a
      difficult entity to diagnose and to manage. This retrospective study analyzed the
      outcome of care for 34 patients who presented with headaches as one of their
      primary sinonasal complaints and were subsequently found to have contact points
      between the nasal septum and one or more turbinates on nasal endoscopy and/or
      computed tomography scan. Following functional endoscopic sinus surgery to
      relieve the contact points, these patients were interviewed regarding
      preoperative and postoperative intensity and frequency of the headaches and the
      overall response of the chronic sinusitis and headaches to surgery, after a mean
      follow-up period of 13.9 months. After surgery, reduction in intensity and
      frequency of headaches was experienced in 91% and 85% of the patients,
      respectively. This investigation demonstrates that surgical management of contact
      point headaches can make a significant impact on the headache symptomatology in
      children and adults.

PMID- 9591549
TI  - Quantitative cytology of nasal secretions with perennial allergic rhinitis in
      children: comparison of noninfected and infected conditions.
AB  - This study was performed to quantify the number of inflammatory cells in nasal
      secretions from pediatric patients with perennial allergic rhinitis under
      noninfected and infected conditions. Nasal secretions were obtained from seven
      children under both noninfected and infected conditions with perennial allergic
      rhinitis to house dust mites, and secondary quantitative cytology was performed
      on the secretions. The number of neutrophils under infected condition was
      significantly higher than that under noninfected condition (P < .05), whereas the
      number of eosinophils in infected condition was significantly lower than that in
      noninfected condition (P < .05). The ratio of eosinophil count to neutrophil
      count was more than 0.1 in noninfected condition. The ratio was significantly
      decreased in infected condition (P < .02). These results suggest that the
      distribution of inflammatory cells in the nasal mucus of children with allergic
      rhinitis would be modified under infected condition.

PMID- 9591551
TI  - Role of the external nasal dilator in the management of nasal obstruction.
AB  - The aim of this study is to evaluate the effect of an external nasal dilator in
      patients with nasal obstruction secondary to mucosal congestion (n = 33) or to
      septal deviation in the nasal valve area (n = 28). A group of subjects with
      healthy nasal cavities was tested also (n = 51). Acoustic rhinometric and
      rhinomanometric nasal measurements were performed with and without the dilator
      and before and after topical decongestion of the nasal mucosa. A visual analog
      scale was employed to evaluate the subjective sensation of nasal obstruction.
      Objective measurements showed that the external dilator increased the minimum
      cross-sectional area and decreased the nasal resistance significantly in all
      three groups (P < 0.01). The effect was more impressive in patients with septal
      deviation (P < 0.001). Subjective assessments reflected patency in all subjects
      except those in the mucosal swelling group (P = 0.06). From this study the
      authors conclude that the external nasal dilator offers an effective, nonsurgical
      therapeutic approach in the management of septal deviation that obstructs the
      nasal valve area. Although patients with nasal obstruction secondary to mucosal
      congestion showed objective improvement with the nasal dilator, these changes
      were not accompanied by a sensation of enhanced patency.

PMID- 9591550
TI  - Immunotherapy decreases seasonal rise in serum-soluble CD23 in seasonal allergic
      rhinitis.
AB  - There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of
      potentiating IgE synthesis, but the in vivo physiologic significance remains to
      be established. This study investigated the seasonal changes in sCD23 in patients
      with seasonal allergic rhinitis. It included 112 adult patients with seasonal
      allergic rhinitis due to Japanese cedar pollens and 20 nonatopic healthy
      volunteers. The 64 patients of the pharmacotherapy group were treated with
      nonsedating antihistamine tablets alone throughout the pollen season and the
      remaining 48 patients of the immunotherapy group continued to be treated with
      immunotherapy. Serum concentrations of sCD23 were measured in each patient,
      before and during the pollen season of 1996, by a sandwich enzyme-linked
      immunosorbent assay. The serum levels of sCD23 in the pharmacotherapy group
      before the pollen season were significantly higher than those in the nonatopic
      group (P = .0130) and those in the immunotherapy group (P = .0316). Seasonal
      increase in sCD23 was significant in the pharmacotherapy group, irrespective of
      the clinical response (P < .0001). By contrast, sCD23 was not significantly
      increased in the good responders to immunotherapy (P = .1826), but was
      significantly increased in the poor responders to immunotherapy (P = .0052). A
      significant correlation between seasonal increase in rate in specific IgE and
      seasonal increase in rate in sCD23 was confirmed in both the pharmacotherapy
      group (rs = 0.321, P = .0107) and the immunotherapy group (rs = 0.474, P =
      .0012). In conclusion, seasonal rise in sCD23 is associated with and is probably
      involved in seasonal rise in specific IgE in patients with seasonal allergic
      rhinitis, and successful immunotherapy is capable of blunting seasonal increase
      in sCD23, thus resulting in attenuation of seasonal increase in specific IgE and
      clinical benefits during the pollen season.

PMID- 9591552
TI  - Epithelial cell proliferation, apoptosis, and apoptosis inhibition in inverted
      papillomas.
AB  - Inverted papillomas (IPs) are rare benign tumors of nasal epithelium with high
      recurrence rates and malignant transformation potential. Their etiology is still
      uncertain, and the mechanism of their growth has not yet been fully described.
      The purpose of this study was to detect, quantify, and compare cell
      proliferation, apoptosis, and apoptosis inhibition in hyperplastic epithelium
      from IPs and in inflammatory nasal polyps (NPs). IP samples were obtained after
      surgical removal of tumor in 13 patients, and NPs were sampled during endoscopic
      ethmoidectomy in 10 patients with nasal polyposis. Cell proliferation and
      apoptosis inhibition, respectively, were assessed by immunohistochemical
      identification of the proliferating cell nuclear antigen (PCNA) and the
      oncoprotein Bcl-2. Apoptosis was evaluated by analyzing the DNA fragmentation.
      Cell proliferation and apoptosis were significantly higher in IPs than in NPs (P
      = .0002 and P = .043, respectively), while apoptosis inhibition was significantly
      lower in IPs than in NPs (P = .001). Concerning IPs, cell proliferation was
      significantly higher than apoptosis (P = .0029) and apoptosis inhibition (P =
      .0015). The increase in epithelial cell proliferation seemed to be greater in IPs
      with dysplasia than in IPs without dysplasia. Increased epithelial cell
      proliferation, but not apoptosis and apoptosis inhibition, seems to be involved
      in the development of IP.

PMID- 9591553
TI  - Videoendoscopic swallowing study for diagnosis of Zenker's diverticuli.
AB  - The videoendoscopic swallowing study (VESS) provides an efficient, cost-effective
      method for swallowing evaluation in the clinic. Previously thought to be of
      little value for disorders of the proximal esophagus, this retrospective study (n
      = 33) demonstrates a high level of sensitivity (85%) and specificity (86%) of
      VESS for detecting Zenker's diverticuli in patients with symptoms of swallowing
      dysfunction. Furthermore, the key finding of postswallow reflux into the
      hypopharynx reliably distinguishes cricopharyngeus dysfunction from diverticuli
      in this population. This study shows that VESS can provide useful information
      about the proximal esophagus.

PMID- 9591554
TI  - Viscosities of implantable biomaterials in vocal fold augmentation surgery.
AB  - Vocal fold vibration depends critically on the viscoelasticity of vocal fold
      tissues. For instance, phonation threshold pressure, a measure of the "ease" of
      phonation, has been shown to be directly related to the viscosity of the
      vibrating mucosa. Various implantable biomaterials have been used in vocal fold
      augmentation surgery, with implantation sites sometimes close to or inside the
      mucosa. Yet their viscosities or other mechanical properties are seldom known.
      This study attempts to provide data on viscosities of commonly used phonosurgical
      biomaterials. Using a parallel-plate rotational rheometer, oscillatory shear
      experiments were performed on implantable polytetrafluoroethylene (Teflon or
      Polytef; Mentor Inc., Hingham, MA), collagen (Zyderm; Collagen Corp., Palo Alto,
      CA), glutaraldehyde crosslinked (GAX) collagen (Phonagel or Zyplast; Collagen
      Corp.), absorbable gelatin (Gelfoam; Upjohn Co., Kalamazoo, MI), and human
      abdominal subcutaneous fat. Samples of human vocal fold mucosal tissues were also
      tested. Under sinusoidal oscillatory shear at 10 Hz and at 37 degrees C, the
      dynamic viscosity was 116 Pascal-seconds (Pa-s) for polytetrafluoroethylene, 21
      Pa-s for gelatin, 8-13 Pa-s for the two types of collagen, 3 Pa-s for fat, and 1
      to 3 Pa-s for vocal fold mucosa. Results extrapolated to 100 Hz also show similar
      differences among the biomaterials, but all values are an order of magnitude
      lower because of the typical inverse frequency relation (shear thinning effect)
      for polymeric and biologic materials. The data suggest that the use of fat for
      vocal fold augmentation may be more conducive to the "ease" of phonation because
      of its relatively low viscosity, which is closest to physiologic levels. This
      implication is probably the most relevant in predicting initial outcome of the
      postoperative voice before there is any significant assimilation (e.g.,
      resorption and fibrosis) of the implanted biomaterial.

PMID- 9591555
TI  - New laryngeal muscle weakness in post-polio syndrome.
AB  - The authors describe the clinical presentations of post-polio laryngeal muscle
      weakness in three patients with prior polio infection who presented with new
      complaints including slowly progressive dyspnea, dysphagia, and/or hoarseness.
      Evaluations by laryngeal videostroboscopy and electromyography revealed vocal
      cord abductor and/or adductor weakness, recurrent posterior glottic web in one
      case, and, in the two patients who agreed to electromyography, evidence of prior
      denervation and reinnervation in laryngeal muscles. Treatment was directed at
      attempting to maintain an airway and optimize vocal quality. One patient
      benefitted from tracheostomy, one benefitted from vocal cord medialization, and
      one benefitted from resection of interarytenoid scarring. The authors conclude
      that diagnosis of laryngeal post-polio syndrome is facilitated by laryngeal
      electromyography. Interventions directed at maintaining an appropriate airway and
      optimizing vocal quality may be helpful.

PMID- 9591556
TI  - Malignant transformation of recurrent respiratory papillomatosis associated with
      integrated human papillomavirus type 11 DNA and mutation of p53.
AB  - Recurrent respiratory papillomatosis (RRP), usually confined to the nasopharynx,
      trachea, and larynx, occasionally can progress to extensive bronchopulmonary
      disease. Most cases of bronchopulmonary and laryngeal papillomatosis are
      cytologically benign and do not undergo malignant transformation; however,
      squamous cell carcinoma (SCC) can arise in RRP in the absence of known risk
      factors such as radiation and smoking. In this study, the authors investigated
      molecular genetic alterations occurring in a case of metastasizing SCC that arose
      in long-standing bronchopulmonary papillomatosis. Genomic DNA from tracheal
      papillomata, tracheobronchial papillomata, SCC of the lung, and a lymph node
      metastasis was extracted. The physical state of the human papillomavirus type 11
      (HPV-11) DNA was investigated by two-dimensional gel electrophoresis. Molecular
      genetic alterations of the host genome were studied by direct sequencing of
      polymerase chain reaction-amplified gene fragments and restriction fragment
      length polymorphism (RFLP) analysis. Episomal and integrated forms of HPV-11
      sequences were detected in histologically benign tumors, but only the integrated
      form of the viral DNA could be found in malignant tissue samples. Molecular
      genetic studies revealed that an allelic loss of the interferon-beta gene
      (IFNbeta-1) and an endogenous type of mutation of the p53 antioncogene were found
      only in the malignant lesions. Mutations were not observed in the ras, neu, or
      multiple tumor suppressor (MTS1/p16) genes in any specimens. The authors' data
      indicated that the p53 genetic mutation was associated with integration of HPV-11
      in histologically malignant lesions. This association may promote a progressive
      genetic instability that can lead to the development and clonal expansion of
      malignant lesions in RRP.

PMID- 9591557
TI  - Primary subglottic cancer.
AB  - This retrospective study reviews 39 patients with primary subglottic cancer seen
      between 1955 and 1988 by the Department of Otolaryngology at Washington
      University. This number constitutes 1.8% of laryngeal cancer cases diagnosed
      during this period. Twenty-eight patients (71.8%) had epidermoid cancer, of which
      19 (67.9%) had "early" disease (stages I and II), and nine (32.1%) had "advanced"
      (stages III and IV). Overall 5-year survival was 57.7%. Disease-free survival was
      46.2%. Patients treated with radiotherapy alone, surgery alone, or both had
      disease-free 5-year survivals of 22.2%, 41.7%, and 100%, respectively.
      Combination therapy showed a significantly higher (P < .01) disease-free survival
      than radiotherapy alone.

PMID- 9591558
TI  - A prospective quality of life study of patients with laryngeal carcinoma by tumor
      stage and different radiation therapy schedules.
AB  - This study was designed to prospectively monitor the quality of life of laryngeal
      cancer patients, to compare the quality of life of patients with small tumors
      with that of patients with large tumors, and to test any quality of life
      difference in patients with small tumors treated with conventional versus
      hyperfractioned accelerated radiation therapy. Patients having had a laryngectomy
      within the study year were also analyzed separately. The European Organization
      for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire
      (QLQ-C30), the EORTC Head and Neck Module (H&N-37), and the Hospital Anxiety and
      Depression (HAD) scale were administered six times during 1 year. These
      questionnaires were found to be suitable for measuring laryngeal cancer patients'
      quality of life longitudinally. The questionnaires were sensitive to differences
      in quality of life for small versus large tumors and showed that hyperfractioned
      accelerated radiation therapy was advantageous compared with conventional
      radiation therapy with respect to quality of life at the 1-year follow-up.

PMID- 9591559
TI  - Radiation therapy for early stage (T1-T2) sarcomatoid carcinoma of true vocal
      cords: outcomes and patterns of failure.
AB  - Sarcomatoid carcinoma of head and neck mucosal sites is a rare high-grade
      malignancy that may cause diagnostic and therapeutic controversies. A
      characteristic of this entity consistently reported but not entirely validated is
      its relative radioresistance and the general belief is that surgery is the
      treatment of choice. The objective of this retrospective study was to determine
      if patients treated with radiation for early glottic sarcomatoid carcinoma had
      worse outcomes than those achieved with irradiation for the more typical squamous
      cell carcinoma. Twenty-eight cases of early stage (T1-T2) sarcomatoid carcinoma
      of the larynx treated with definitive doses of megavoltage irradiation between
      1969 and 1995 at The University of Texas M. D. Anderson Cancer Center form the
      cohort for this analysis. All pathologic material was reviewed to confirm the
      diagnosis. All tumors manifested spindle cell features with marked
      cytomorphologic abnormalities characteristic of this entity. Sixteen tumors (57%)
      had the more typical polypoid gross morphology of sarcomatoid carcinoma. Twenty
      one patients (75%) were staged T1 and seven patients (25%) had stage T2 disease.
      All patients were treated with small laryngeal fields, median size 20 cm2, and to
      a median dose of 65 Gy. Follow-up ranged from 1.5 to 24 years (median, 10 years).
      Four patients (14%) had local disease recurrence, and all had salvage total
      laryngectomies and remained free of local disease. The 5-year actuarial local
      control rates for patients with T1 and T2 lesions were 94% and 54%, respectively.
      Only one patient developed regional and distant disease. The 10-year actuarial
      disease-specific and overall survival rates were 92% and 63%, respectively.
      Patients with early stage sarcomatoid carcinoma of the glottis treated with
      radiation had similar control rates to irradiated patients with similar volume
      disease with the more typical squamous cell carcinoma. The authors contend that
      the histologic diagnosis of sarcomatoid carcinoma by itself should not influence
      the decision to treat a patient with early stage glottic disease with
      irradiation.

PMID- 9591560
TI  - Prognostic significance of depth of invasion in cancer of the larynx.
AB  - To determine the prognostic significance of depth of invasion in laryngeal
      cancer, the depth of invasion of tumor was measured with an ocular micrometer on
      the laryngectomy specimens of 94 surgically treated patients with T1, T2, and T3
      laryngeal cancer and was expressed in millimeters. There was a significant
      negative correlation between the depth of invasion and disease-free survival. The
      tumors with no clinical involvement of regional lymph nodes in neck (NO neck) had
      significantly less depth of invasion than those with involvement (N+ neck). The
      tumors with pathologically confirmed cervical lymph node metastasis had
      significantly more depth of invasion than those without metastasis. For tumors
      with a depth of invasion equal to or greater than 3.25 mm, the rate of cervical
      metastasis in this study has always been significantly higher than for those with
      a depth of invasion less than 3.25 mm (P < .05). The mean depths of invasion for
      cases with and without recurrence were not significantly different. According to
      the multivariate analysis, depth of invasion (P = .047) and patient age (P =
      .113) significantly affected the disease-free survival independently. The depth
      of invasion did not significantly affect the recurrence and the interval between
      surgery and the development of recurrence (P > .15). The depth of invasion should
      be measured in every laryngectomy specimen. The depth of invasion influences the
      cervical metastasis and disease-free survival significantly but does not affect
      the recurrence rate. The depth of invasion plays an independent role in
      determining the disease-free survival.

PMID- 9591561
TI  - Visualization of the glottis through a laryngeal mask during medialization
      laryngoplasty.

PMID- 9591562
TI  - Intraoperative use of methylene blue to localize parathyroid adenoma.

PMID- 9591563
TI  - A novel technique to facilitate Zenker's diverticulectomy.

PMID- 9591565
TI  - Prostate cancer with leg pain.

PMID- 9591566
TI  - The rectilinear scanner and an enduring legacy of education and research.

PMID- 9591564
TI  - Doppler stethoscope for planning composite microvascular flaps in head and neck
      reconstruction.

PMID- 9591567
TI  - The Department of Energy's role in isotope availability for nuclear medicine
      research.

PMID- 9591569
TI  - Stress myocardial perfusion SPECT in women: is it the cornerstone of the
      noninvasive evaluation?

PMID- 9591568
TI  - Diagnostic accuracy of technetium-99m-MIBI myocardial SPECT in women and men.
AB  - Noninvasive diagnosis of coronary artery disease in women has some limitations
      due to a higher percentage of false-positive results. In addition, a lower
      prevalence of disease can be observed in this population. In this study, we
      evaluated the diagnostic accuracy of 99mTc-methoxy-isobutyl-isonitrile (MIBI)
      SPECT in women and men, in a group of patients with proven coronary artery
      disease by coronary angiography (select minority) and in all patients where a
      noninvasive test (silent majority) was performed. METHODS: Seven hundred and two
      consecutive patients without previous myocardial infarction were studied with
      99mTc-MIBI myocardial SPECT. One hundred sixty-three patients had coronary
      angiography (select minority) and 539 did not (silent majority). All patients
      underwent exercise stress testing, and simultaneous dipyridamole was administered
      in 32% of patients who did not achieve maximum predicted heart rates. Diagnostic
      accuracy of the test was calculated for the select minority. Then, sensitivity
      and specificity of the silent majority were recalculated according to the Diamond
      criteria. RESULTS: Prevalence of coronary artery disease (32% versus 80%, p =
      0.0001) and peak O2 consumption achieved in exercise tests (watts, exercise
      duration) were lower in women. The probability of positive results of 99mTc-MIBI
      SPECT also was lower in women (34% versus 65%). The sensitivity of 99mTc-MIBI
      SPECT in women of the select minority was lower (85% versus 93%, p = 0.01),
      whereas there was no significant difference for specificity (91% versus 89%).
      After correcting the results for the silent majority, there were no significant
      differences in sensitivity (87% versus 88%) and specificity (91% versus 96%)
      between women and men. These results were not different for patients who achieved
      maximum predicted heart rates during stress testing (without dipyridamole
      administration). CONCLUSION: The sensitivity of 99mTc-MIBI myocardial SPECT in
      women was lower than in men when only the select minority was considered. When
      the silent majority was considered (correction of selection bias) sensitivity and
      specificity results did not differ significantly between the sexes.

PMID- 9591570
TI  - PET evaluation of cerebral hemodynamics in occlusive cerebrovascular disease pre-
      and postsurgery.
AB  - We studied cerebral blood flow (CBF), oxygen extraction fraction (OEF), transit
      time (TT) and hemodynamic reserve capacity using acetazolamide (ACZ) in both the
      pre- and postoperative states, and evaluated the effect of surgery on the
      cerebral hemodynamics. METHODS: Twelve patients with a unilateral occlusive
      cerebral artery were studied. Among them, seven patients had extracranial
      intracranial (EC-IC) bypass surgery, while the remaining five patients had
      carotid endarterectomies. The CBF was measured using the (15)O-water bolus
      injection method in a resting state, 5 and 20 min after intravenous ACZ (1 g),
      while the OEF and TT were measured by the (15)O steady state method. The values
      of these parameters were obtained by regions of interest set over the cerebral
      hemisphere on both sides, and which then were compared between the pre- and
      postoperative states using the paired Student's t-test. RESULTS: The t values
      were 1.36 (CBF at rest), 2.97 (CBF at 5 min after intravenous ACZ), 1.40 (CBF at
      20 min after intravenous ACZ), 2.00 (OEF) and -0.86 (TT) on the surgical side,
      and -0.16, 0.21, 0.22, -0.47 and 0.61 on the nonsurgical side, respectively. The
      t values of the ACZ response (% increase in CBF) were 3.07 (5 min after
      intravenous ACZ) and 0.72 (20 min) on the surgical side, and 1.03 and 0.90 on the
      nonsurgical side, respectively. A significant change was observed only in the CBF
      studies 5 min after intravenous ACZ. CONCLUSION: PET can demonstrate significant
      cerebral hemodynamic change after surgery, especially in CBF measurement 5 min
      after intravenous ACZ, and may therefore be useful for evaluating cerebral
      hemodynamics pre- and postsurgery.

PMID- 9591571
TI  - SPECT imaging in cerebral vasospasm following subarachnoid hemorrhage.
AB  - Cerebral vasospasm is a frequent complication after subarachnoid hemorrhage and
      contributes to overall morbidity and mortality. Arteriography is the standard
      test for determining the presence of vasospasm. A retrospective review of 16
      patients with cerebral aneurysm was undertaken to assess the sensitivity and
      specificity of SPECT for diagnosis of vasospasm. Fourteen patients were
      hospitalized after subarachnoid hemorrhage and 2 patients were hospitalized for
      elective aneurysmal clipping. The patients' condition on discharge was correlated
      to clinical and SPECT evidence of vasospasm. METHODS: Vasospasm was defined as
      the new onset of neurological signs and symptoms not explained by rebleed or
      hydrocephalus. A total of 20 SPECT studies were performed for 16 patients during
      their admission and 14 of 16 patients had a single angiographic study. RESULTS:
      Thirteen of 16 patients had 14 episodes of clinical evidence of vasospasm and 14
      SPECT studies were performed in these 13 patients. The sensitivity and
      specificity of SPECT in this retrospective study were 89% (8/9) and 71% (5/7),
      respectively. Our small sample of arteriograms yielded in comparison a
      sensitivity of 67% (2/3) and specificity of 100% (9/9). The one false-negative
      SPECT study occurred in conjunction with the one false-negative arteriogram in
      the presence of clinical findings consistent with vasospasm. Three false-positive
      SPECT studies occurred in 2 patients who had perfusion abnormalities in areas of
      normal CT findings without clinical or arteriographic evidence of vasospasm. Five
      of 5 patients who died became unresponsive as a result of clinically presumed
      vasospasm and 4 of 5 of these patients had diffuse or hemispheric SPECT perfusion
      defects. Of the 11 patients who survived, none became unresponsive; 1 of 11 had
      positive diffuse or hemispheric perfusion defects. CONCLUSION: SPECT is a
      sensitive and fairly specific test for corroboration of clinical findings of
      vasospasm. A negative SPECT study may obviate the need for arteriography.
      Unresponsiveness is the best predictor of poor outcome; however, hemispheric
      SPECT perfusion deficits are also associated with poor outcome.

PMID- 9591572
TI  - HMPAO brain SPECT in acute carbon monoxide poisoning.
AB  - Technetium-99m-hexamethylpropylene amine oxime (HMPAO) brain images with fanbeam
      SPECT, in combination with surface three-dimensional display, were used to detect
      basal ganglion and cerebral cortex anomalies in the acute phase of carbon
      monoxide (CO) poisoning. METHODS: Ten patients, aged 16-29 yr, with acute CO
      poisoning and no past history of neurologic disorders were enrolled in this
      study. After oxygen treatment, all 10 patients were investigated using 99mTc
      HMPAO brain images with fanbeam SPECT and surface three-dimensional display.
      Meanwhile, 6 of 10 patients also received a brain CT scan. RESULTS: CT scan
      findings were negative in all 6 patients. Fanbeam SPECT demonstrated unilateral
      or bilateral hypoactivity of basal ganglia in 6 patients. Local hypoactivity
      anomalies were found in the brain cortex of 7 patients, using surface three
      dimensional display of the brain. Only 2 of 10 patients had normal 99mTc-HMPAO
      brain images. CONCLUSION: This study suggests that, in comparison with
      traditional brain imaging techniques, 99mTc-HMPAO brain imaging with fanbeam
      SPECT in combination with surface three-dimensional display is a better tool for
      early detection of regional cerebral anomalies in acute CO poisoning.

PMID- 9591573
TI  - Technetium-99m-HMPAO brain SPECT in Sjogren's syndrome.
AB  - Technetium-99m-hexamethylpropylene amine oxime (HMPAO) brain images with fanbeam
      SPECT, in combination with surface three-dimensional display, were used to detect
      basal ganglion and cerebral cortex anomalies in Sjogren's syndrome patients.
      METHODS: Forty-eight female Sjogren's syndrome patients with normal brain CT or
      magnetic resonance imaging findings were enrolled in this study and were
      investigated using 99mTc-HMPAO brain images with fanbeam SPECT and surface three
      dimensional display. These patients were separated into two subgroups. Group 1
      consisted of 38 patients with definite neuropsychiatric symptoms/signs and Group
      2 consisted of 10 patients without any neuropsychiatric symptoms/signs. RESULTS:
      Fanbeam SPECT demonstrated unilateral or bilateral hypoactivity of basal ganglia
      and thalamus in 14% and 0% of patients in Groups 1 and 2, respectively. Using
      surface three-dimensional display of the brain, local hypoactivity anomalies were
      found in the brain cortex of 53% and 20% of patients in Groups 1 and 2,
      respectively. In Group 1 patients, parietal lobes were the most common areas of
      brain involvement. The cerebellum and thalamus were the least common areas of
      brain involvement. In Group 2 patients, parietal and temporal lobes were the most
      common areas of brain involvement. CONCLUSION: This study suggests that 99mTc
      HMPAO brain imaging with fanbeam SPECT, in combination with surface three
      dimensional display, is a sensitive tool for detecting regional cerebral
      anomalies in Sjogren's syndrome patients with and without neuropsychiatric
      symptoms/signs.

PMID- 9591574
TI  - Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose
      and/or carbon-11-methionine.
AB  - This study evaluates the usefulness of PET for the preoperative evaluation of
      brain gliomas and methods of quantification of PET results. METHODS: Fifty-four
      patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG)
      (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of
      visual analysis, calculation of glucose consumption and five tumor-to-normal
      brain ratios for both tracers were correlated with two histologic grading systems
      and with follow-up. RESULTS: Visual analysis (for FDG) and tumor-to-mean cortical
      uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET
      results. Methionine was proven to be better than FDG at delineating low-grade
      gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly
      correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We
      showed a good correlation between FDG PET and histologic grading. MET uptake
      could not differentiate between low-grade and anaplastic astrocytomas but was
      significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited
      high uptake of FDG and MET, probably depending more on oligodendroglial cellular
      differentiation than on proliferative potential. Uptake was decreased in
      anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be
      taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas
      and oligodendrogliomas, because of a discrepancy between high PET metabolism and
      low proliferative potential (good prognosis). Both tracers proved useful for the
      prediction of survival prognosis. Methionine proved slightly superior to FDG for
      predicting the histologic grade and prognosis of gliomas, despite the
      impossibility of differentiation between Grades II and III astrocytomas with MET.
      This superiority of MET could be explained by patient sampling (low number of
      Grade III gliomas submitted to examination with both tracers). The combination of
      both tracers improved the overall results compared to each tracer alone.
      CONCLUSION: Both tracers are useful for the prediction of the histologic grade
      and prognosis. The apparent superiority of MET over FDG could be due to the small
      number of Grade III gliomas studied with both tracers.

PMID- 9591575
TI  - Decreased brain glucose utilization in patients with Cushing's disease.
AB  - Glucocorticoid hormones affect glucose use in different tissues, and the results
      of several experimental studies have suggested that glucocorticoids have a
      central action on cerebral metabolism. PET, using the radiotracer 18F
      fluorodeoxyglucose (FDG), permits the measurement of cerebral glucose metabolism.
      METHODS: To investigate whether cerebral glucose metabolism would be altered in
      patients with increased plasma glucocorticoid levels, we analyzed the FDG PET
      studies that were done on 13 patients with Cushing's disease and compared the
      results with those obtained in 13 age-matched normal control subjects. A second
      FDG PET scan was performed on 4 patients after surgical removal of the pituitary
      adenoma. RESULTS: Patients with Cushing's disease had a significant reduction in
      cerebral glucose metabolism compared with normal controls. In the patients on
      whom a second PET scan was performed, there was a trend toward increased glucose
      metabolism on the second scan when comparing pre- and postsurgery values for each
      patient. CONCLUSION: We suggest that the decreased cerebral glucose metabolism we
      observed in Cushing's disease is attributable to increased glucocorticoid levels,
      and we speculate that abnormal cerebral glucose metabolism might contribute to
      the cognitive and psychiatric abnormalities that are frequently observed in
      patients with Cushing's disease.

PMID- 9591576
TI  - Technetium-99m-ECD SPECT fails to show focal hyperemia of acute herpes
      encephalitis.
AB  - This is a case of herpes simplex encephalitis (HSE) examined with 99mTc-ethyl
      cysteinate dimer (ECD) and 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT.
      Static images obtained with 99mTc-ECD showed a reduced tracer uptake of the
      temporal lobe but focal hyperactivity using 99mTc-HMPAO. Dynamic images indicated
      regional increase of cerebral blood perfusion with both tracers. Technetium-99m
      ECD had rapid washout from the inflamed tissue, while 99mTc-HMPAO had avid
      uptake. Hypofixation of 99mTc-ECD leads to failure to detect the characteristic
      finding of temporal lobe hyperemia in acute HSE.

PMID- 9591577
TI  - Reproducibility of the distribution of carbon-11-SCH 23390, a dopamine D1
      receptor tracer, in normal subjects.
AB  - The reproducibility of [11C]SCH 23390 in PET was studied in 10 normal human
      subjects. METHODS: The scan-to-scan variation of several measures used in PET
      data analysis, including the radioactivity ratio, plasma-input Logan total
      distribution volume (DV), plasma-input Logan DV ratio (DVR) and tissue-input
      Logan Bmax/Kd values, was determined. RESULTS: There were significant
      correlations among the radioactivity ratio, plasma-input DVR and tissue-input
      Bmax/Kd. With the cerebellum as the reference region, these three measures also
      had high reliability (86%-95%), high between-subject s.d. (7.7%-11.3%) and small
      within-subject s.d. (2.3%-3.6%), indicating that they are comparable and useful
      measures for the assessment of dopamine D1 receptor binding. CONCLUSION: The
      radioactivity ratio and the tissue-input Bmax/Kd may be preferred methods for the
      evaluation of dopamine D1 receptor binding because these two methods do not
      require arterial blood sampling and metabolite analysis. Our results show that
      cerebellum is a reliable reference region for SCH 23390. When the Logan plasma
      input function method is used in data analysis for SCH 23390, DVRs rather than
      total DV values should be used because of the poor reliability of the DV values
      and their lack of correlation with other measures. Carbon-11-SCH 23390 is thus a
      reliable and reproducible ligand for the study of dopamine D1 receptor binding by
      PET.

PMID- 9591578
TI  - Detection of melanoma metastases with thallium-201 scintigraphy.
AB  - Thallium-201 accumulates well in various malignant tumors. The aim of this study
      was to evaluate the potential of 201Tl imaging in patients with metastatic
      melanoma. METHODS: Fifty patients with suspected melanoma metastases were studied
      after intravenous injection of a mean tracer activity of 100 MBq 201Tl-chloride.
      We took sequence images up to 5 min (15 sec/image) and immediate whole-body
      images with a double-headed camera and a high-resolution collimator. RESULTS: Of
      36 patients with metastatic melanoma confirmed by histopathology, metastases were
      detected in 28 patients using 201Tl imaging. The tumor-to-background ratio ranged
      from 2.0 to 4.5 (mean 3.2). There were 8 patients with false-negative findings
      (sensitivity = 78%). Five false-negative findings were lymph nodes greater than
      1.5 cm with tumor-to-background ratios lower than 1.5. Only a few cutaneous
      metastases smaller than 1 cm could be detected. There was one false-positive
      finding of an inflamed lymph node. The optimum time for imaging was 2-5 min
      postinjection. CONCLUSION: These data suggest that 201Tl imaging is an accurate
      method for the detection of melanoma metastases. The short waiting period after
      injection, the lack of side effects and the sensitivity of about 80% may qualify
      this method as a routine investigation in patients with high-risk melanoma.

PMID- 9591579
TI  - Technetium-99m-tetrofosmin uptake in brain tumors by SPECT: comparison with
      thallium-201 imaging.
AB  - Thallium-201 is clinically used for the assessment of primary and recurrent brain
      tumors. The biologic properties of 201Tl that allow it to accumulate within the
      tumor cells render 201Tl useful in evaluating tumor malignancy, but its physical
      characteristics and nonroutine availability limits its use in some institutions,
      as compared to 99mTc-labeled compounds. The aim of this study was to assess the
      feasibility of using 99mTc-tetrofosmin for imaging brain tumors and to compare
      its uptake with that of 201Tl. METHODS: Twenty-six patients with 27 intracranial
      masses were studied with SPECT. In the first group of seven patients (Group A),
      the timing for optimal acquisition of the 99mTc-tetrofosmin scan was assessed. In
      the second group of 19 patients (Group B), two sequential 201Tl (74-148 MBq
      intravenous) and 99mTc-tetrofosmin (740-925 MBq intravenous) studies were
      performed 20 min after tracer injection and compared. RESULTS: In Group A, no
      significant difference in the tumor-to-background (T/B) ratio among the 20-, 40-
      and 120-min postinjection studies was observed. In Group B, the quality of
      reconstructed images with 99mTc-tetrofosmin, judged visually, was superior to
      that of 201Tl in 47% of all studies and was comparable in the remaining 53%. A
      significant relationship between 201Tl and 99mTc-tetrofosmin T/B ratio (r = 0.75,
      p < 0.01) was found. The T/B ratio of 99mTc-tetrofosmin was significantly higher
      than that of 201Tl (23.3 +/- 21.5 compared to 6.1 +/- 2.9, p < 0.005).
      CONCLUSION: Technetium-99m-tetrofosmin is a suitable radiotracer for the imaging
      of intracranial lesions with SPECT. Moreover, a better definition of tumor
      margins and a higher contrast between neoplastic and normal brain tissue can be
      achieved.

PMID- 9591581
TI  - Fluorine-18-fluorodeoxyglucose assessment of glucose metabolism in bone tumors.
AB  - In our study, we investigate the glucose metabolism of various types of bone
      lesions with 18F-fluorodeoxyglucose (FDG) PET. METHODS: Twenty-six patients
      showing clinical and radiographic symptoms of a malignant bone tumor were
      included. Histological examination after the PET study revealed 19 malignant and
      7 benign tumors. PET images were corrected for attenuation. Arterial blood
      samples were taken to establish the input function. The metabolic rate of glucose
      consumption (MRglc) was calculated for the whole tumor, for the 10 pixels with
      maximum activity and for contralateral normal muscle tissue. RESULTS: All lesions
      were clearly visualized with 18F-FDG PET except for a small infarction of the
      humerus. All the other lesions had increased glucose metabolism compared to
      surrounding and contralateral muscle tissue. Both maximum and average MRglc for
      benign, as well as malignant, lesions were significantly higher than for
      contralateral normal tissue. The maximum and average MRglc were not higher for
      malignant as opposed to benign lesions. There was a large overlap between the
      MRglc of benign and malignant lesions. CONCLUSION: Fluorine-18-FDG PET appears
      suitable to visualize bone tumors. With the quantification of glucose metabolism,
      it is not possible to differentiate between benign and malignant bone tumors.
      There does not seem to be a clear correlation between the MRglc and the biologic
      aggressiveness of the neoplasms.

PMID- 9591580
TI  - Thallium-201 scintigraphy to predict therapeutic outcome of iodine-131 therapy of
      metastatic thyroid carcinoma.
AB  - We studied the relationship between 201Tl uptake and the efficacy of radioiodine
      therapy in thyroid carcinoma. METHODS: Forty-four patients with metastases of
      well-differentiated thyroid carcinoma received 201Tl scintigraphy within the 2 mo
      before their initial 131I therapy. Patients were classified into two groups
      according to the tumor-to-background (T/B) ratio on the late 201Tl scan: high
      201Tl uptake (T/B > or = 2.1) and low 201Tl uptake (T/B < 2.1). The therapeutic
      outcome was judged by the percent reduction in the tumor diameter at 6 mo after
      the treatment. The treatment was defined as effective when the tumor showed more
      than 50% reduction in the tumor diameter. The patients in whom radioiodine was
      ineffective were followed up to determine if the tumor showed further growth.
      RESULTS: Of the 44 patients, 25 had high 201Tl uptake and 19 had low 201Tl
      uptake. The therapy was effective in 15 patients and was ineffective in 29. All
      the patients in whom radioiodine was effective had low 201Tl uptake. On the other
      hand, 25 of 29 patients in whom radioiodine was ineffective had high 201Tl
      uptake. Eight patients, in whom radioiodine was ineffective despite good 131I
      uptake, had high 201Tl uptake. There were no significant differences in the
      positive predictive value and the negative predictive value for effective
      treatment between 201Tl scintigraphy and therapeutic dose 131I scintigraphy.
      Among the 25 patients in whom radioiodine was ineffective and who had high 201Tl
      uptake, the tumor diameter increased in 7 (28%). However, none of the tumors with
      low 201Tl uptake increased in size during the follow-up period. CONCLUSION:
      Thallium-201 scintigraphy has a high predictive value for the efficacy of
      radioiodine therapy in metastatic thyroid carcinoma. Thus, it is helpful in
      determining the indication for radioiodine therapy and it seems to be an adjunct
      to tracer dose 131I scintigraphy.

PMID- 9591582
TI  - FDG PET for detection and therapy control of metastatic germ cell tumor.
AB  - We investigated the use of PET and 2[18F]fluoro-2-deoxy-D-glucose (FDG) for
      detection and therapy control of metastatic germ cell cancer in comparison to CT.
      METHODS: Fifty-four PET studies were performed in addition to CT in 33 patients
      with histopathologically proven germ cell tumors (14 seminomas, 18 nonseminomas,
      1 not classified). The scans were done either after initial diagnosis (Group 1; n
      = 12), within 2 wk after completion of chemotherapy (Group 2; n = 13) or 14-375
      days after chemotherapy (Group 3; n = 29). PET and CT were validated either by
      histology (n = 19) or clinical follow-up for 182-1704 days (n = 35). Focal
      pathological uptake with PET was quantified using standardized uptake values
      (SUVs). RESULTS: PET was significantly more accurate than CT (0.86 versus 0.59; p
      < 0.025) for detection of residual viable tumor in Group 3. While sensitivities
      of PET and CT did not differ markedly, PET was significantly more specific than
      CT. No significant differences between PET and CT were found in Groups 1 and 2.
      PET scans after therapy resulted in false-negative findings in five of nine cases
      of Group 2 but only in two of nine cases of Group 3. False-positive PET findings
      occurred in three inflammatory processes. SUV of seminomas was significantly
      higher than in nonseminomas (p < 0.01). CONCLUSION: PET using FDG is superior to
      CT for assessment of residual tumor after chemotherapy of germ cell cancer and
      may thus have an increased effect on patient management in the future. PET must
      be performed at least 2 wk after completion of therapy. Further data are
      necessary to determine the role of FDG PET for initial staging of germ cell
      cancer.

PMID- 9591583
TI  - Hurthle cell tumor dwelling in hot thyroid nodules: preoperative detection with
      technetium-99m-MIBI dual-phase scintigraphy.
AB  - Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc
      MIBI was used to differentiate benign and malignant hot thyroid nodules. METHODS:
      Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule
      on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN)
      underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the
      administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess
      nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T)
      uptake ratio in the early and late image and the washout rates (WO) from the
      nodule and thyroidal tissue were measured. All patients underwent thyroid
      surgery. RESULTS: Histopathology revealed a Hurthle cell tumor in three nodules,
      a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma
      without oxyphilic cells in the remaining 10 nodules. The Hurthle cell tumor
      nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/-
      0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule
      was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign
      nodules showed intense uptake in the early image and intense uptake to absent
      retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early
      and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the
      thyroidal tissue was 20.33 +/- 2.92). CONCLUSION: Single injection dual-phase
      99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result
      of the activity of a Hurthle cell tumor, since these tumors cause intense and
      persistent tracer uptake in contrast with a benign AFTN.

PMID- 9591584
TI  - Biologic dosimetry in thyroid cancer patients after repeated treatments with
      iodine-131.
AB  - To estimate a cumulative dosimetric index that reflects the dose to the
      circulating lymphocytes after repeated treatments with 131I, biologic dosimetry
      was applied to 18 patients with differentiated thyroid carcinoma and neck relapse
      or lung metastases. METHODS: Chromosomal aberrations were scored in peripheral
      blood samples that were obtained before and 4 days after each administration of
      3.7 GBq 131I according to two methods, conventional cytogenetics and chromosome 4
      painting. RESULTS: The mean dosimetric index was equal to 0.5 Gy by both methods
      after the administration of 3.7 GBq 131I. Repeated administrations of 131I
      delivered the same dose each time, resulting in a cumulative dose from 1-3.5 Gy
      in the patients who had two to seven treatments. However, the estimated dose,
      based on the number of chromosomal aberrations on Day 4 and, above all, from the
      third treatment on, was considerably lower than the real dose absorbed by the
      lymphocytes. This may be linked to the phenomenon of apoptosis, which results in
      a loss of information during the course of repeated irradiation. CONCLUSION: Both
      chromosomal painting and conventional cytogenetics underestimate the cumulative
      dose after repeated 131I treatments. A complementary test measuring apoptosis may
      improve the dose estimates.

PMID- 9591585
TI  - Evaluation of the in vivo biodistribution of yttrium-labeled isomers of CHX-DTPA
      conjugated monoclonal antibodies.
AB  - We evaluated the in vivo stability and biodistribution of four isomers (CHX-A',
      CHA-A", CHX-B' and CHX-B") of 2-(p-isothiocyanatobenzyl)-cyclohexyl
      diethylenetriaminepentaaceti c acid (CHX-DTPA), a recently developed backbone
      substituted derivative of DTPA. METHODS: The ligands were conjugated to
      monoclonal antibody B3, a murine IgG1 kappa, and labeled with 88Y at 55.5-66.6
      MBq/mg (1.5-1.8 mCi/mg). Nontumor-bearing nude mice were injected intravenously
      with 55.5-66.6 kBq (1.5-1.8 microCi) of 88Y-labeled B3 conjugates and with 125I
      labeled B3 as an internal control. The mice were then killed at 6, 24, 48, 96 and
      168 hr postinjection. RESULTS: At 168 hr, the concentration of 88Y in processed
      bone of either CHX-A' [4.6% injected dose (ID)/g] or CHX-A" (4.0%ID/g) was less
      than that of either the CHX-B' (21.9%ID/g) or B" (12.1%ID/g) ligands. The two
      ligands CHX-B" and CHX-B' were not acceptable for yttrium labeling of antibody
      because of their high and progressive bone accumulation. The accumulation of 88Y
      in bone of CHX-B' was five times greater than that of CHX-A' at 168 hr. The CHX
      A" cleared from the circulation slightly faster than CHX-A' without releasing the
      yttrium and showed the lowest uptake by bone of any of the four isomers. The
      accumulation in the other normal organs was similar for all four isomers of 88Y
      CHX-B3 conjugates. CONCLUSION: Although the CHX-B" and CHX-B' were not acceptable
      for labeling with yttrium, the CHX-A' and CHX-A" were suitable, indicating that
      differences in stereochemistry can greatly influence stability of radionuclide in
      the chelate.

PMID- 9591586
TI  - Divalent cobalt as a label to study lymphocyte distribution using PET and SPECT.
AB  - PET and SPECT allow the study of the distribution of lymphocytes in living
      humans, provided that these cells are adequately prelabeled ex vivo. Such a
      labeling technique should not only be nontoxic to lymphocytes but it also should
      take into consideration that their kinetics are such that radioactivity must be
      followed for at least 24 hr. We describe the potential of divalent cobalt
      isotopes (55Co2+, half-life 17.5 hr for PET; 57Co2+, half-life 270 days for
      SPECT) for labeling lymphocytes. METHODS: Isolated rat lymphocytes were incubated
      with 57CoCl2 with or without unlabeled CoCl2 or CaCl2 carrier or other compounds.
      In some experiments, the accumulation of radioactive cobalt and calcium in
      lymphocytes was determined in the presence of phorbol myristate acetate alone,
      calcimycine alone or in combination. The toxicity of cobalt to lymphocytes was
      assessed with the trypan blue exclusion test and by assessing their proliferative
      capacity using radioactive thymidine incorporation as a readout. Biodistribution
      of cobalt-labeled lymphocytes was determined with postmortem analysis and
      compared with that of the free (nonlymphocyte-bound) tracer. RESULTS: At high
      concentrations (more than 100 x necessary for adequate labeling), cobalt was not
      cytotoxic. Incubation of labeled lymphocytes in tissue culture medium for 24 hr
      in vitro showed a loss of less than half of the incorporated cobalt
      radioactivity. Twenty-four hours after in vitro labeling of lymphocytes and
      intravenous injection, radioactivity accumulated not only in the liver, kidney
      and bladder of the rat but in the spleen and lungs, which differed from the
      distribution of the free tracer. Uptake and binding to rat lymphocytes of Co2+
      partly mimicked that of Ca2+. The binding of cobalt, however, was stronger and
      nonsaturable. CONCLUSION: These results warrant further exploration of cobalt as
      a PET or SPECT label of human lymphocytes.

PMID- 9591587
TI  - Yttrium-90-DOTA-peptide-chimeric L6 radioimmunoconjugate: efficacy and toxicity
      in mice bearing p53 mutant human breast cancer xenografts.
AB  - The novel radioimmunoconjugate, 90Y-DOTA-peptide-chimeric L6 (ChL6), was designed
      to reduce radiation to critical normal tissues with an exceptionally stable 90Y
      chelate moiety and a biodegradable linker. Human breast cancer tumors (HBT 3477)
      in mice were treated with 90Y-DOTA-peptide-ChL6 to examine the effects of
      increasing dose on the therapeutic efficacy and toxicity of this new agent.
      METHODS: Groups of athymic mice bearing HBT 3477 xenografts received 4.1- to 14.1
      MBq doses of 90Y-DOTA-peptide-ChL6 intravenously. The lethal dose (LD)(50/30),
      general well-being (weight loss), hematotoxicity and therapeutic efficacy were
      studied. RESULTS: The LD(50/30) was 12.8 MBq, which corresponded to doses of 17.9
      and 50.9 Gy to the total body and tumor (200 mm3), respectively. Deaths were
      associated with hematotoxicity; no deaths occurred at doses of 9.6 MBq or less.
      At sublethal doses, the rate of tumor response (cures +/- complete responses +
      partial responses) increased with increasing dose: 4.1 MBq, 27%; 5.9 MBq, 41%;
      8.5 MBq, 69%; and 9.6 MBq, 79% (maximum tolerated dose, MTD). In mice receiving
      doses of 4.1-9.6 MBq, 6 of 74 (8%) of tumors were cured. Increasing the 90Y dose
      led to smaller tumor size at nadir and longer tumor regrowth delay but no
      increase in cure. Although the HBT 3477 p53 gene was found to be mutant resulting
      in p53 protein not binding DNA breaks, tumors at MTD demonstrated evidence of
      apoptosis. CONCLUSION: In the human breast cancer athymic mouse model, 90Y-DOTA
      peptide-ChL6 had a high therapeutic index and LD(50/30) leading to a 79% response
      rate at the MTD. The evidence of apoptosis as a mechanism for this tumor response
      in p53 mutant breast cancer warrants further studies because these observations
      are relevant to the treatment of lethal breast cancer.

PMID- 9591589
TI  - Quantitative imaging of iodine-131 distributions in brain tumors with pinhole
      SPECT: a phantom study.
AB  - A method of quantitatively imaging 131I distributions in brain tumors from
      intratumoral administration of activity was developed and investigated using
      pinhole SPECT of brain tumor phantoms. METHODS: Pinhole SPECT sensitivity and
      resolution were characterized using 131I point-source acquisitions with high
      resolution lead (1.4-mm diameter aperture) and tungsten (1.0-mm diameter
      aperture) pinhole inserts. SPECT scans were obtained from brain tumor phantoms in
      a water-filled cylinder. The tumor phantoms consisted of spheres filled with an
      131I solution to model intratumoral administration of radiolabeled monoclonal
      antibodies. Two spheres were 20.5 and 97 ml, and two other concentric spheres
      modeled a tumor with a high-activity shell (71.5 ml) and a low-activity core (21
      ml). The collimator focal length was 16 cm and the distance from the pinhole to
      the center of rotation was 13 cm. The filtered backprojection reconstruction
      algorithm incorporated scatter and attenuation compensation. SPECT tumor
      activities and concentrations were estimated using scaling factors from reference
      point-source scans. RESULTS: System sensitivities for point sources at the center
      of rotation were 28.4 cts/sec(-1) MBq(-1) (lead insert) and 13.6 cts/sec(-1) MBq(
      1) (tungsten insert). SPECT resolutions (FWHM) at the center of rotation were 8.1
      11.9 mm (lead) and 6.7-10.3 mm (tungsten). Total tumor activity estimates from
      SPECT were within 17% of the true activities. SPECT activity concentration
      estimates in small regions of interest (ROIs) averaged -20% for the 20.5-ml
      sphere, -11% for the 97-ml sphere, -39% for the shell and +20% for the core of
      the shell-core phantom. Activity spillover due to limited spatial resolution and
      the tails of the system response functions biased the estimates. The shell-to
      core activity concentration ratio of 4.1 was better estimated with the tungsten
      insert (2.3) than with the lead insert (1.9) due to better resolution.
      CONCLUSION: Pinhole SPECT is a promising technique for imaging and quantifying
      total 131I activity in regions the size of brain tumors. Relative errors were
      greater for activity concentration estimates in small ROIs than for total
      activity estimates.

PMID- 9591588
TI  - Technetium-99m-sestamibi scintimammography for the detection of breast carcinoma:
      comparison between planar and SPECT imaging.
AB  - The purpose of our study was to compare the results of planar and SPECT
      scintimammography for the detection of breast carcinoma. In addition, our goal
      was to determine whether SPECT reconstructed with filtered backprojection (FBP)
      or with iterative algorithms (ISA) can improve the sensitivity and specificity of
      planar scintimammography (SMM). METHODS: One hundred thirteen patients with
      suspicious physical examinations and/or mammography underwent planar lateral and
      anterior breast imaging as well as SPECT imaging after injection of 99mTc
      sestamibi. We used a blind evaluation, both separately and combined, for planar
      SMM, ISA-SPECT and FBP-SPECT. Scintigraphic findings were correlated with the
      final histopathological diagnoses. RESULTS: The sensitivity of planar SMM was 80%
      with a specificity of 83%. All ISA-SPECT studies were of diagnostic quality,
      while FBP-SPECT was considered nondiagnostic in 14 that were excluded for
      statistical calculation. Sensitivity of ISA-SPECT and FBP-SPECT were 71% and 69%,
      respectively. Specificity was 70% for ISA-SPECT and 66% for FBP-SPECT. Combined
      planar SMM plus ISA-SPECT sensitivity was 85% (81% for planar SMM plus FBP-SPECT)
      with a specificity of 72%. Three carcinomas indeterminate on planar SMM were
      correctly identified by combined planar SMM plus ISA-SPECT. ISA-SPECT and FBP
      SPECT provided additional information to planar SMM with respect to localization
      of sestamibi uptake, tumor extent, improved diagnostic certainty and detection of
      axillary nodes in 40 and 14 patients, respectively. CONCLUSION: ISA
      reconstruction is the preferable approach to SPECT data. Combined with planar
      SMM, ISA-SPECT can improve sensitivity. SPECT is useful in cases of indeterminate
      and positive planar SMM.

PMID- 9591590
TI  - Gastric emptying in children.
AB  - This article reviews the evaluation of gastric emptying in children with emphasis
      on scintigraphic techniques. The mechanism of emptying as well as how
      quantitation may vary with patient positioning, the composition of the standard
      meal and possibly the size of the meal are discussed. Preliminary data suggest
      that for children under the age of 2 yr, meal size is less critical. Although
      normal ranges need to be determined by individual laboratories, values reported
      in the literature may be used as a guide. Quantitation is useful for the follow
      up of patients on therapy.

PMID- 9591592
TI  - Clinical usefulness of technetium-99m-HMPAO-labeled leukocyte scan in prosthetic
      vascular graft infection.
AB  - The infection of a prosthetic vascular graft (PVGI), although rare, is the most
      severe complication in reconstructive vascular surgery. The early diagnosis of
      this complication reduces the death rate from surgery. Aortofemoral graft
      infections differ clinically from peripheral graft infections in significant
      ways. The aim of this article is to evaluate separately the reliability of the
      99mTc-HMPAO-labeled leukocyte scan or white blood cell count (WBC) in the early
      detection of both aortofemoral and peripheral graft infections. METHODS: One
      hundred sixty-two WBCs were performed on 129 consecutive patients with suspected
      aortofemoral (122 scans) and peripheral (40 scans) graft infection and in a 12
      patient control group. Patients with suspected PVGI were categorized into three
      groups on the basis of their signs and symptoms on readmission: (a) patients with
      specific signs of graft infection (Group A); (b) patients with nonspecific signs
      of graft infection (Group B); and (c) patients with anastomotic aneurysms (Group
      C). Gram's stains of the perigraft exudate and graft cultures were performed and
      used as the gold standard in patients who underwent surgery. An 18-mo clinical
      follow-up was done to assess the presence or absence of graft infection in
      patients who did not have surgery. RESULTS: In patients with suspected
      aortofemoral graft infections, the overall sensitivity, specificity and accuracy
      of WBCs (Groups A, B, C) were 100%, 92.5% and 97.5%, respectively, whereas
      sensitivity, specificity and accuracy calculated in the patients with nonspecific
      signs of graft infection (Groups B, C) were 100%, 92.3% and 96.9%, respectively.
      In patients with suspected peripheral graft infections, sensitivity, specificity
      and accuracy were 100%. CONCLUSION: The white blood cell scan seems a reliable
      diagnostic method for early diagnosis of PVGI, and it is more useful in
      aortofemoral graft infections.

PMID- 9591591
TI  - Thyroglobulin and low-dose iodine-131 and technetium-99m-tetrofosmin whole-body
      scintigraphy in differentiated thyroid carcinoma.
AB  - Determination of thyroglobulin (Tg) levels, determined under endogenous thyroid
      stimulating hormone stimulation after withdrawal of L-thyroxin treatment (off
      T4), has been proven to be the most sensitive method for evaluation of patients
      with recurrent malignancy or distant metastases. This study uses a comparative
      approach between low-dose 131I scan and the previously reported highly sensitive
      99mTc-tetrofosmin whole-body scintigraphy, using Tg-off-T4 as a basis for
      comparison. METHODS: Fifty-eight consecutive patients of our follow-up program
      with primary thyroid carcinoma ablated with thyroidectomy and radioiodine therapy
      were examined after L-thyroxin withdrawal over 3-4 wk with 131I (185 MBq) and
      99mTc-tetrofosmin whole-body scintigraphy and Tg determination (off-T4) within 5
      days. Patients with Tg levels above 0.5 ng/ml were defined as Group A (n = 29).
      Group B (n = 29) comprised patients who had Tg levels (off-T4) below 0.5 ng/ml.
      RESULTS: Iodine-131 revealed only 19 of 44 tumor sites (43.18%). Additionally,
      three remnants could be demonstrated. Sensitivity showed decreasing values for
      local recurrences (4 of 7, 57.1%), bone lesions (7 of 13, 53.85%) and mediastinal
      (2 of 4, 50%), lung parenchymal (3 of 7, 42.85%) and lymph node (2 of 9, 22.2%)
      metastases. Whole-body scintigraphy with 99mTc-tetrofosmin revealed a total of 39
      of 44 malignant lesions (88.6%). Sensitivity was superior for lung parenchymal
      metastases (9 of 9, 100%), mediastinum (4 of 4, 100%) and lymph nodes (9 of 10,
      90%) and inferior for bone metastases (11 of 13, 84.6%). Local recurrences could
      be detected in 6 of 7 patients (85.7%), and thyroid remnants were detected in 2
      cases (2 of 11, 18.2%). One liver metastasis could not be detected because of the
      physiologic tracer distribution of 99mTc-tetrofosmin. Thyroglobulin-off-T4
      detected malignant recurrence or metastases in 18 of 19 patients (94.7%) when a
      cutoff of 3 ng/ml was used and in 16 of 19 patients (84.2%) when a cutoff of 10
      ng/ml was used. Specificity was calculated as 71.8% when a cutoff of 0.5 ng/ml
      was used, 89.7% when a cutoff of 3 ng/ml was used and 100% when a cutoff of 10
      ng/ml was used. CONCLUSION: Scintigraphy with 99mTc-tetrofosmin showed clear
      advantages concerning sensitivity in most metastatic lesions when compared with
      low-dose 131I scan. Despite a slight lower specificity, 99mTc-tetrofosmin whole
      body scintigraphy has, therefore, been proven to be a useful tool in the
      assessment of metastatic lesions in differentiated thyroid carcinoma.

PMID- 9591593
TI  - Dexamethasone treatment and plasma glucose levels: relevance for fluorine-18
      fluorodeoxyglucose uptake measurements in gliomas.
AB  - Dexamethasone (DEX) is frequently used in brain tumor management. This study
      investigated the effect of DEX treatment and plasma glucose levels on 18F
      fluorodeoxyglucose (FDG) uptake in patients with malignant gliomas (16
      glioblastoma, 3 anaplastic astrocytoma). METHODS: Fifteen DEX-treated patients
      (mean relative dose 0.23 +/- 0.15 mg(-1) x kg(-1) x day(-1), range 0.07-0.53),
      four patients not treated with DEX and nine healthy subjects were studied using
      PET and FDG. PET data obtained from tumors and the contralateral cortex were
      fitted to a standard two-tissue compartment model. The FDG transport and
      phosphorylation rates, distribution volume (DV), steady-state accumulation (Ki),
      deoxyglucose metabolism (R), plasma volume as well as standardized uptake values
      (SUVs) and tumor-to-brain ratios were determined. In addition, the tumor size was
      estimated from the maximal area of contrast-enhancing tumor on computed cranial
      tomography (CCT) scans or MRI. RESULTS: FDG uptake was depressed in the
      contralateral cortex of patients and was related to tumor size. With increasing
      relative DEX dose, a decrease in the DV of tumors (linear regression p = 0.021)
      and in the DV (p = 0.109) and plasma volume (p = 0.010) of contralateral cortex
      was found. R, Ki and SUVs in tumors and contralateral cortex were not related to
      the relative DEX dose. With increasing plasma glucose levels, differential
      decreases in Ki and SUVs in tumors (p = 0.057 and p = 0.733, respectively) and
      contralateral cortex (p = 0.001 and p = 0.029, respectively) were observed.
      CONCLUSION: The data suggest that DEX affects FDG uptake in malignant gliomas
      through interaction with cerebral blood vessels and extracellular space, whereas
      FDG metabolism in tumors is not influenced substantially. This is of practical
      importance for patients having serial brain tumor imaging for treatment
      evaluation because patients may receive different DEX doses at different time
      points in the course of their disease. By contrast, the plasma glucose level must
      be considered a confounding variable when SUVs, tumor-to-brain ratios or Ki are
      used for treatment evaluation.

PMID- 9591594
TI  - Organ-specific insulin resistance in patients with noninsulin-dependent diabetes
      mellitus and hypertension.
AB  - Abnormal heart and skeletal muscle glucose metabolism in diabetes or essential
      hypertension has been demonstrated. However, the role of hypertension in heart
      and skeletal muscle glucose utilization in diabetes has not been clarified yet.
      METHODS: We compared heart and skeletal muscle glucose utilization using PET and
      the whole-body glucose disposal rate (GDR) during insulin clamping in 9 patients
      with noninsulin-dependent diabetes mellitus (NIDDM) and essential hypertension
      and 11 patients with NIDDM without hypertension to examine the effect of
      hypertension on heart and skeletal muscle glucose utilization. Results also were
      compared with those for 8 asymptomatic healthy control participants. RESULTS:
      Skeletal muscle glucose utilization rate was comparable between hypertensive
      NIDDM patients (61.2 +/- 55.5 micromol x min(-1) x kg(-1)) and normotensive NIDDM
      patients (50.9 +/- 25.2 micromol x min(-1) x kg(-1)) but was significantly
      reduced in both groups compared with control subjects (94.2 +/- 57.3 micromol x
      min(-1) x kg(-1)), as was the GDR (25.2 +/- 11.3 and 24.0 +/- 7.5 micromol x min(
      1) x kg(-1)), respectively, for patients compared with 38.5 +/- 11.5 micromol x
      min(-1) x kg(-1) for control participants). However, the myocardial glucose
      utilization (MGU) rate was significantly reduced in NIDDM patients without
      hypertension (389 +/- 185 micromol x min(-1) x kg(-1)) than in those with
      hypertension (616 +/- 86.4 micromol x min(-1) x kg(-1), p < 0.01). Multivariate
      stepwise regression analysis has shown that MGU was significantly correlated with
      systolic blood pressure and plasma free fatty acid concentration. CONCLUSION:
      Whole-body insulin resistance was observed in NIDDM patients independent of
      hypertension. The MGU rate may have different properties to oppose insulin
      resistance than glucose utilization of skeletal muscle in hypertensive patients
      with NIDDM.

PMID- 9591595
TI  - Three-dimensional surface display of dynamic pulmonary xenon-133 SPECT in
      patients with obstructive lung disease.
AB  - To better perceive abnormal regional ventilation in patients with obstructive
      lung disease, a three-dimensional display was applied to dynamic pulmonary 133Xe
      SPECT. METHODS: Dynamic SPECT was performed using a triple-detector SPECT system
      in 30 patients with obstructive disease, 13 patients with restrictive disease and
      7 normal subjects. After reconstructing color-illuminated, surface-rendered three
      dimensional images of equilibrium and 3-min washout (WO3), a single three
      dimensional fusion display was created from these two different time-course image
      sets in which a three-dimensional WO3 image indicating 133Xe retention was
      transparently visible through three-dimensional equilibrium image delineating
      lung contours. The three-dimensional equilibrium and WO3 images were created by a
      25% threshold of the 133Xe maximal pixel activity (MPA) in equilibrium data.
      Besides, a three-dimensional WO3 image with a 18% threshold [mean + 2 s.d. ratios
      (%) of the MPA in WO3 data to that in equilibrium data in normal subjects] was
      used for assessing the presence of retention compared to normal lungs. RESULTS:
      The 18% threshold three-dimensional WO3 image showed abnormal retention in
      obstructive diseases but not in restrictive diseases. The three-dimensional
      fusion display provided an overview of localized retention in obstructive
      diseases and enhanced the perception of their spatial relationships and extent
      compared to those on multislice tomograms. The extent of retention correlated
      well with %FEV1 (r = 0.813) and 133Xe clearance-time (T(1/2)) (r = 0.912).
      CONCLUSION: This topographic modality for 133Xe SPECT is helpful for the better
      perception of anatomic distributions of 133Xe retention and interstudy
      comparisons of ventilation abnormality in patients with obstructive disease.

PMID- 9591596
TI  - Extraskeletal uptake of technetium-99m-MDP in sites of heparin administration.
AB  - A 19-yr-old woman with juvenile diabetes and protein C deficiency was referred
      for a bone scan to rule out osteomyelitis of the right tibia. The bone scan did
      not reveal evidence of osteomyelitis. There was, however, extraskeletal uptake of
      the 99mTc bone tracer in the anterior abdominal wall confined to the sites of
      subcutaneous heparin administration. This case is presented because of its
      interesting scintigraphic findings and to discuss the association of protein C
      deficiency and heparin administration as a cause of extraskeletal 99mTc bone
      tracer accumulation.

PMID- 9591597
TI  - Transferrin-dependent uptake and dosimetry of Auger-emitting diagnostic
      radionuclides in human spermatozoa.
AB  - Localization of Auger-emitting radionuclides within spermatozoa could lead to the
      induction of transmissible genetic damage. We have quantified in vitro uptake of
      the widely used diagnostic Auger-emitters, (111)In and 99mTc, by ejaculated human
      spermatozoa and investigated the role of transferrin in their cellular
      localization. The resultant dose to sperm heads, including cellular dosimetry for
      Auger emissions, has been calculated for each radionuclide and compared with that
      achieved using conventional macrodosimetry. METHODS: Freshly isolated human
      spermatozoa were incubated in a physiological salt solution containing (111)In
      chloride, 99mTc-pertechnetate or the transferrin-binding isotope 59Fe-citrate as
      a positive control. Cellular uptake mechanisms were investigated with transferrin
      competition and temperature dependence studies. The percentage uptake of each
      radionuclide was determined, and the dose to individual sperm heads was
      calculated using both conventional macrodosimetric methods and by consideration
      of radionuclide localization and energy deposition at the cellular level,
      including Auger electron emissions from (111)In and 99mTc. RESULTS: On in vitro
      incubation, human spermatozoa were found to accumulate (111)In and 59Fe but not
      99mTc. Cell uptake of (111)In and 59Fe was transferrin-mediated; however, an
      alternative transferrin-independent uptake pathway was also present for (111)In.
      The dose to sperm heads from (111)In, calculated using measured uptake and
      cellular dosimetry, was found to be larger than that calculated using
      conventional dosimetry by a factor of more than 100. In contrast, conventional
      dosimetry was adequate for 99mTc and 59Fe. CONCLUSION: Isolated human spermatozoa
      appear to accumulate transferrin-binding isotopes, such as the Auger-emitter
      (111)In. If this uptake mechanism operates in the male reproductive tract, the
      resultant high dose to the sperm head could indicate that contraception may be
      advisable after large diagnostic doses of (111)In and, possibly, other
      transferrin-binding radionuclides. Such precautions could prevent transmission of
      any genetic damage from irradiated spermatozoa.

PMID- 9591598
TI  - In vitro demonstration of synergy between radionuclide and chemotherapy.
AB  - Radionuclide therapy is currently used in the treatment of some malignancies,
      including hepatocellular carcinoma. The effects of external beam radiotherapy are
      improved by combining it with chemotherapy. The aim of this study was to
      determine whether such a synergistic effect could be demonstrated in vitro with
      internal radiation therapy. METHODS: HepG2 cells were cultured from Day 0 to Day
      8 under the following conditions: exposure for 4 hr on Day 2 to increasing
      concentrations of 5-fluorouracil (5FU), doxorubicin or cisplatin (CDDP); exposure
      from Day 2 to Day 8 to increasing concentrations of 131-iodide; exposure on Day 2
      to low-toxicity doses of drugs for 4 hr, followed by exposure to 131I at
      increasing concentrations; and exposure to increasing concentrations of 131I from
      Day 2 to Day 8, with exposure for 4 hr on Day 6 to the drugs. Cell toxicity was
      assessed by enzyme release (lactate dehydrogenase and aspartate aminotransferase)
      in the culture medium and on cell survival (protein and tetrazolium dye test).
      All cultures were run in triplicate. RESULTS: A dose- and time-dependent toxicity
      was demonstrated with doxorubicin and CDDP but not with 5FU. When HepG2 cells
      were exposed to 131I, the toxicity was rather low, but significant, and was time-
      and dose-dependent. Treating these cells with combination radiotherapy and
      chemotherapy resulted in a toxicity that was significantly greater than that with
      131I or chemotherapy drugs alone. CONCLUSION: The radiosensitivity of HepG2 cells
      is low; combining a chemotherapeutic drug with a radiotherapeutic agent improves
      the radiosensitivity in a synergistic fashion. This combination is thus able to
      strengthen the therapeutic effect of internal radiation therapy in different
      malignancies, particularly in hepatocellular carcinoma.

PMID- 9591599
TI  - Correction for partial volume effects in PET: principle and validation.
AB  - The accuracy of PET for measuring regional radiotracer concentrations in the
      human brain is limited by the finite resolution capability of the scanner and the
      resulting partial volume effects (PVEs). We designed a new algorithm to correct
      for PVEs by characterizing the geometric interaction between the PET system and
      the brain activity distribution. METHODS: The partial volume correction (PVC)
      algorithm uses high-resolution volumetric MR images correlated with the PET
      volume. We used a PET simulator to calculate recovery and cross-contamination
      factors of identified tissue components in the brain model. These geometry
      dependent transfer coefficients form a matrix representing the fraction of true
      activity from each distinct brain region observed in any given set of regions of
      interest. This matrix can be inverted to correct for PVEs, independent of the
      tracer concentrations in each tissue component. A sphere phantom was used to
      validate the simulated point-spread function of the PET scanner. Accuracy and
      precision of the PVC method were assessed using a human basal ganglia phantom. A
      constant contrast experiment was performed to explore the recovery capability and
      statistic error propagation of PVC in various noise conditions. In addition, a
      dual-isotope experiment was used to evaluate the ability of the PVC algorithm to
      recover activity concentrations in small structures surrounded by background
      activity with a different radioactive half-life. This models the time-variable
      contrast between regions that is often seen in neuroreceptor studies. RESULTS:
      Data from the three-dimensional brain phantom demonstrated a full recovery
      capability of PVC with less than 10% root mean-square error in terms of absolute
      values, which decreased to less than 2% when results from four PET slices were
      averaged. Inaccuracy in the estimation of 18F tracer half-life in the presence of
      11C background activity was in the range of 25%-50% before PVC and 0%-6% after
      PVC, for resolution varying from 6 to 14 mm FWHM. In terms of noise propagation,
      the degradation of the coefficient of variation after PVC was found to be easily
      predictable and typically on the order of 25%. CONCLUSION: The PVC algorithm
      allows the correction for PVEs simultaneously in all identified brain regions,
      independent of tracer levels.

PMID- 9591600
TI  - Use of stabilized technetium-99m-exametazime for radiolabeling leukocytes.
AB  - With a stabilizing agent (i.e., methylene blue and sodium phosphate buffer
      mixture), the in vitro stability of 99mTc-exametazime has been increased to 4-6
      hr postreconstitution. However, it is not feasible to use the stabilized 99mTc
      exametazime for leukocyte radiolabeling. This is due to the deep blue appearance
      of the mixture of stabilized 99mTc-exametazime and blood components, which makes
      it impossible to separate properly the supernatant from the leukocyte button. In
      our study, we have developed a practical methodology for overcoming this
      difficulty in order to use stabilized 99mTc-exametazime in leukocyte labeling.
      METHODS: The stabilized 99mTc-exametazime preparation used in our method
      consisted of 2 ml 7.4-8.0 GBq (200-215 mCi) 99mTc and 2 ml methylene
      blue/phosphate buffer solution. The separated leukocytes from 80-ml fresh venous
      blood were incubated with three different ages (i.e., 0-, 4-, or 6-hr
      postreconstitution) of stabilized 99mTc-exametazime (approximately 925 MBq,
      approximately 25 mCi; 0.5-1 ml) at room temperature for 15 min. After incubation,
      3 ml of 12.6% ACD/NS solution (anticoagulant citrate dextrose, solution A, USP
      mixed with 0.9% NaCl, v/v) was added to the tube and centrifuged at 160 g for 5
      min. Three milliliters of the dark blue supernatant were carefully removed, and
      the bottom 1 ml portion was resuspended with 9 ml of 12.6% ACD/NS solution. After
      centrifugation (160 g for 5 min), the supernatant was clear enough to be drawn
      off without disturbing the radiolabeled leukocyte button. The white cell button
      was then resuspended in 4 ml of platelet-poor plasma. RESULTS: The overall
      labeling efficiency (LE) of our new technique was 67.8%-91.9%, with the higher LE
      associated with fresher stabilized 99mTc-exametazime. During a 6-hr in vitro
      stability evaluation, radiolabeled leukocytes lost 1.2% +/- 0.3% (n = 24), 1.3%
      +/- 0.1% (n = 16) and 1.8% +/- 0.1% (n = 16) each hour of the cell-bound 0-, 4-,
      and 6-hr-old 99mTc-exametazime, respectively. The 99mTc-exametazime-labeled
      leukocytes examined by the trypan blue staining technique at 6-hr
      postradiolabeling yielded nonstained cells indicating viable leukocytes.
      CONCLUSION: We concluded that with a small volume of 99mTc-exametazime and double
      dilution steps with 12.6% ACD/NS solution, stabilized 99mTc-exametazime can be
      used effectively for leukocyte radiolabeling with a high LE and long in vitro
      stability.

PMID- 9591601
TI  - Procedure guideline for myocardial perfusion imaging. Society of Nuclear
      Medicine.

PMID- 9591602
TI  - Procedure guideline for brain perfusion SPECT using technetium-99m
      radiopharmaceuticals. Society of Nuclear Medicine.

PMID- 9591603
TI  - MIRDOSE 3.1 gives erroneous results under windows NT.

PMID- 9591604
TI  - Iodine-123-iomazenil SPECT in Alzheimer's disease.

PMID- 9591605
TI  - Quantification of left ventricular function with thallium-201 myocardial gated
      SPECT.

PMID- 9591606
TI  - Is technetium-99m-MIBI a relevant tracer to tumor response to chemotherapy of
      bone lesions?

PMID- 9591607
TI  - Time for a change?

PMID- 9591608
TI  - Gene radiotherapy; gene targeted versus targeted by gene product.

PMID- 9591609
TI  - Functional brain imaging.

PMID- 9591610
TI  - Technetium-99m-HMPAO brain SPECT in systemic lupus erythematosus with central
      nervous system involvement.

PMID- 9591611
TI  - Continuous ambulatory radionuclide monitoring of left ventricular function.

PMID- 9591612
TI  - The 1997 Andre Allard lecture. Aviation medicine: the challenges of prevention.

PMID- 9591613
TI  - Evidence of baroreflex adaptation to repetitive +Gz in fighter pilots.
AB  - BACKGROUND: The arterial baroreflex acts to maintain arterial pressure in the
      face of an orthostatic challenge. The high +Gz loads experienced by fighter
      pilots represent an extreme form of orthostatic challenge. G-induced loss of
      consciousness (G-LOC) represents a failure of the baroreflex system to maintain
      the appropriate level of cerebral perfusion. The anecdotal experience of fighter
      pilots is that their cardiovascular systems adapt to frequent exposure to high
      +Gz levels. HYPOTHESIS: The purpose of this study was to demonstrate that the
      baroreflex-mediated cardiovascular response of a group of 8 fighter pilots to a
      mild accelerative stimulus differs from that of a group of 12 non-pilots.
      METHODS: Arterial pressures and heart rate responses to rapid head-up tilting to
      +75 degrees were compared between the two groups. Five variables were examined:
      systolic, diastolic, mean arterial and pulse pressures, and heart rate. RESULTS:
      The cardiovascular responses of the groups were fundamentally different. In
      response to tilt, the non-pilots showed little change in systolic and mean
      arterial pressures, diastolic pressure increased slightly and pulse pressure
      decreased significantly. In the pilot group, however, significant increases were
      observed in systolic, diastolic and mean arterial pressures (p < 0.05), whereas
      pulse pressure did not change. Between groups there were significant differences
      observed in terms of arterial pressures (p < 0.05), but not heart rate.
      CONCLUSION: The baroreflex of a fighter pilot is capable of adapting to +Gz,
      becoming a more sensitive and effective BP control system as a result. This
      adaptation affords the pilot greater protection against G-LOC.

PMID- 9591614
TI  - Psychological studies of a Japanese winter-over group at Asuka Station,
      Antarctica.
AB  - In order to understand the psychological effects of Antarctic isolation and
      confinement on Japanese expeditioners, psychological studies were done on eight
      members of a wintering-over party at Asuka Station between December 1990 and
      February 1992. Mean age of the subjects was 34.8 +/- 5.56 yr. The study includes
      self assessment questionnaires, psychological tests introduced by the Polar
      Psychology Project (PPP), a bibliographical study and photographic measurements.
      There was no pathological depression in midwinter. Subjective and cumulative
      fatigue symptoms were more noticeable in the older individuals. The Telic
      Dominance Scale was significantly correlated with the Anxiety Sensitivity Index.
      The Sense of Coherence Inventory and the Personal View Survey showed an
      interrating correlation. By analyzing a daily group photograph, seasonal
      variations in mood and behavior of individuals have been clarified. Consequently,
      it is hoped that observation of non-verbal signals such as facial expression,
      clothing, and postures may lead to the development of a new methodological
      framework for the long-term plan of psychological investigation of the men under
      severe stress.

PMID- 9591615
TI  - The design of arm pressure covers to alleviate pain in high G maneuvers.
AB  - HYPOTHESIS: Arm pain has been noted especially when increased coverage anti-G
      suits are worn in combination with PBG (pressure breathing during G) in high G
      centrifuge test runs. Arm pain has forced the termination of test runs and has
      the potential to cause a serious decrement in a pilot's ability to function
      effectively during high-G flight. Based on the theory that arm pain is caused by
      fluid pooling in the arm, four new pressure cover systems for the arm were
      designed and tested. METHODS: Seven test subjects wore each design in a series of
      runs in a dynamic flight simulator (DFS). Subjects experienced both gradual and
      rapid onset rate runs with G levels ranging from +3.0 G to +9.0 G. Data were
      collected on the maximum G's achieved, pain location, and pain intensity.
      Subjective responses on the comfort and function of each design and overall arm
      cover design preferences were also obtained via a questionnaire. RESULTS:
      Analysis of the DFS data, using a two-factor ANOVA (subjects, designs), revealed
      that each of the new designs provided significantly better protection from arm
      pain than the control condition (no protection) and that each of the designs
      significantly improved the maximum G level attained during rapid onset
      acceleration in the range of +1 G. CONCLUSION: No positive correlation was found
      between subject ranking of the four new design concepts at the conclusion of the
      study in terms of the pain reduction they provided and the pain levels reported
      during DFS testing.

PMID- 9591616
TI  - Back pain in Australian military helicopter pilots: a preliminary study.
AB  - BACKGROUND: Several studies have highlighted the problem of back pain among
      helicopter pilots, but few have controlled for potential confounding factors in
      their analyses, or sought to examine the effects of back pain on operational
      readiness and flying performance. There have been no previous studies of the
      prevalence of back pain among Australian military pilots. METHODS: The
      prevalence, risk factors, and consequences of low back pain were assessed in a
      cross-sectional survey of 200 Australian military helicopter pilots by self
      completion questionnaire. RESULTS: Responses were received from 131 (66%) of
      available pilots. The overall prevalence of reported back pain was 64% (95% CI
      56%-72%), with a further 28% of pilots describing back discomfort while flying.
      More than half the pilots (55%) indicated that back pain had interfered with
      their concentration while flying, with 16% reporting that they had hurried flying
      missions because of pain. A minority of pilots (7%) had refused to fly because of
      back problems. After adjusting for age, education, BMI, posture and numbers of
      hours flown, multiple logistic regression modelling indicated that a prior
      history of back injury was the most significant predictor of back pain among
      rotary wing pilots (OR 2.63, 95% CI 1.11-6.23). CONCLUSIONS: We conclude that the
      prevalence of back pain in Australian military helicopter pilots is unacceptably
      high and may be limiting operational readiness, pilot performance, flying safety,
      and pilot health. Urgent attention needs to be given to improved ergonomic design
      in aircraft, and both back pain prevention and back injury rehabilitation
      programs.

PMID- 9591617
TI  - Effect of G suit type on cognitive performance.
AB  - BACKGROUND: Sustained acceleration protection ensembles are being developed to
      help pilots of high performance aircraft endure high G exposures for longer
      periods of time. It has been assumed that better G endurance confers better pilot
      task performance. This premise was studied on the Armstrong Laboratory Dynamic
      Environment Simulator centrifuge. METHOD: Human subjects repeatedly endured
      prolonged high-G simulated aerial combat on a centrifuge to the point of loss of
      vision or physical exhaustion. Some profiles included over 20 exposures to +9 Gz.
      While enduring the G exposures, subjects tracked a simulated "bogey" aircraft on
      a visual display and performed a secondary task. Measures of cognitive function
      and physiologic status were taken throughout the exposures. G protection
      ensembles included the standard CSU 13 B/P anti-G suit, the Advanced Technology
      Anti-G Suit (ATAGS), COMBAT EDGE positive pressure breathing system with the CSU
      13 B/P, COMBAT EDGE with ATAGS, and the Northrop Advanced Protection System
      (APS). RESULTS: More advanced protective systems not only allow longer G
      endurance, but provide adequate support for maintained cognitive performance
      throughout the extended exposure. Although measures were affected by the type of
      protective system the subject was wearing, as well as individual ability and
      coping strategies, consistent target tracking task performance, rapid choice
      reaction time, and sufficient arterial oxygen saturation were maintained
      throughout extended exposures to a point preceding termination by only a second
      or two. CONCLUSIONS: Those anti-G protection ensembles that cover and protect the
      body and which employ positive pressure breathing allow longer high G exposures
      which provide support for maintained cognitive performance.

PMID- 9591618
TI  - Use of cytochrome-P450 mono-oxygenase 2 E1 isozyme inhibitors to delay seizures
      caused by central nervous system oxygen toxicity.
AB  - BACKGROUND: The neuronal origins and mechanisms of central nervous system oxygen
      toxicity are only partly understood. Oxygen free radicals are felt to play a
      major role in the production of CNS oxygen toxicity because of the interactions
      of free radicals with plasma membranes producing lipid peroxidation. The
      cytochrome P-450 monooxygenase system IIE1 isozyme is important in the brain.
      This led to trials of P450 monooxygense inhibitors for prevention of oxygen
      toxicity. Diethyldithiocarbonate (DDC) proved to be the most promising agent in
      this class; 21-aminosteroid lazeroid compounds have been successful in
      experimentally limiting pulmonary oxygen toxicity. This led to our trying to
      prevent neuronal oxygen toxicity by the use of 21-aminosteroid and six other
      drugs during hyperoxia. METHODS: In our experiments, mice were placed in an
      oxygen-filled hyperbaric chamber in paired experiments. One pre-treated mouse and
      one control mouse were exposed simultaneously to assess the efficacy of drugs in
      preventing seizures caused by hyperbaric oxygen at 5.1 atmospheres absolute. Time
      to seizure was observed through a port hole in the hull of the hyperbaric
      chamber. RESULTS: DDC, 21-aminosteroid and propranolol produced significant
      delays in the onset of seizures (p < 0.001) with no observable side effects; 1
      aminobenzotriazole and disulfiram produced much shorter delays in the onset of
      seizures caused by hyperbaric oxygen and also had unacceptable side effects.

PMID- 9591619
TI  - Pro-opiomelanocortin activation and simulated interceptor combat flight.
AB  - METHODS: To investigate the influence that psychological workload, associated
      with simulated combat military flight, has on secretion of stress hormones we
      measured concentrations of plasma corticotropin-releasing hormone (CRH), pro
      opiomelanocortin (POMC) related adrenocorticotropin (ACTH), beta-endorphin (BE),
      and cortisol in 10 Finnish Air Force (FAF) military interceptor pilots. They
      performed the same 20-min combat flight mission in a Saab J35 Draken S simulator,
      including four radar attacks during one-on-one situations with increasing
      cognitive tasks and psychological strain. Blood samples were collected -35 min, 1
      min, 30 min and 60 min after the flight mission. Control blood samples were
      collected from the subjects at the same time of day in randomized order before or
      after the flight mission. During the control period the subjects were allowed to
      perform ground duties. RESULTS: Plasma CRH was undetectable in samples drawn
      before or after the flight and control period. Plasma ACTH was significantly (p <
      0.05) elevated before the simulated combat flight when compared with the
      respective value in the control experiment. This is an anticipatory type of
      stress reaction. Plasma BE did not change significantly after the simulated
      flight. Plasma cortisol increased significantly (p < 0.05) 1 min after the
      simulated flight. One of the ten pilots had an extreme POMC and cortisol
      activation after the flight mission, suggesting that the pilot's stress tolerance
      was less than average. CONCLUSIONS: We conclude that stress, produced during
      simulated combat military flight, increases POMC and cortisol secretion. An
      anticipatory-type stress reaction was found to be associated with the simulated
      combat flight, as judged from the increased preflight plasma ACTH.

PMID- 9591620
TI  - Joint NASA-ESA-DARA Study. Part three: characterization of sleep under ambient
      CO2-levels of 0.7% and 1.2%.
AB  - An experiment was conducted to study sleep quality and sleep architecture in
      volunteers living in a closed system under elevated ambient CO2 levels of 0.7%
      and 1.2%. In a closed system, human life is possible only if the CO2 level is
      permanently adjusted. For the Russian space station MIR, for example, the CO2
      levels of the present study are actual upper limits for the adjustment. Sleep
      architecture was found to be altered in astronauts on the orbiting MIR station.
      Sleep quantity and quality were reduced. The latency to the first REM sleep was
      shorter in space and slow wave sleep was redistributed from the first to the
      second sleep cycle. The elevated CO2 concentration in the atmosphere on MIR may
      be one of the reasons for those observations regarding sleep in space. Thus, this
      experiment was also conducted in order to clarify the interpretation of data
      obtained from astronauts on MIR. In this study sleep polygraphies could be
      recorded in 4 subjects who lived for 23 d under 0.7% and then for the same period
      of time under 1.2% CO2. Findings suggest that these levels of ambient CO2 do not
      reduce sleep quality. Sleep architecture, however, was slightly changed and
      showed that the amount of slow wave sleep increased with the duration of the
      exposure to CO2. But it can be excluded that findings on MIR were caused by
      elevated CO2-levels.

PMID- 9591621
TI  - Joint NASA-ESA-DARA Study. Part three: cardiorespiratory response to elevated CO2
      levels during sleep.
AB  - Long-term exposure to elevated ambient CO2-levels is a common condition for
      living in a closed environment such as a spacecraft. In this study, the cardio
      respiratory system response to CO2-levels of 0.7% and 1.2% was assessed. The
      response was investigated during non-REM sleep when the sensitivity of the
      respiratory system to ambient CO2 is low and only subject to the metabolic
      respiratory drive. Four subjects were exposed to 0.7% and 1.2% CO2 for 23 d each.
      Respiration rate and heart rate were determined for the first two phases of slow
      wave sleep. In addition, the occurrence of central apneas was assessed. Data were
      analyzed by a repeated measure ANOVA. As a response to CO2 exposure two dynamic
      effects were observed. Heart rate increased initially with a peak between the
      second and the sixth night. Over the period of the exposure, respiration rate and
      heart rate decreased steadily. At least two mechanisms with different time
      constants must be considered for this dynamic behavior: an uncompensated
      respiratory acidosis, followed by a phase of relative compensation. At the end of
      the 23-d exposure, equilibrium in the physiological state had not been reached.
      Though the experiment did not show severe effects from CO2, it is too early to
      state that a long-term exposure does not have any consequences for health and
      well-being.

PMID- 9591622
TI  - Joint NASA-ESA-DARA Study. Part three: circadian rhythms and activity-rest cycle
      under different CO2 concentrations.
AB  - BACKGROUND: During manned space missions, the actual concentration of carbon
      dioxide (CO2) is frequently elevated to a degree that may affect human
      functioning and productivity. Therefore, a ground-based international study was
      performed that tested various psychological and physiological functions under the
      condition of two different levels of CO2. Thus, a specific experiment aimed at
      the influence of enhanced CO2-concentrations on the sleep-wake cycle and the
      circadian system. METHODS: Four volunteers were subjected to a CO2 concentration
      of 0.7% and 1.2%, respectively, for 24 consecutive days under each condition.
      Before they were exposed to these elevated levels, baseline measurements were
      conducted during 5 d under ambient CO2 concentrations (<0.1%). Circadian
      parameters were assessed by continuous recording of body temperature and by the
      determination of excretion rates of cortisol, 6-hydroximelatoninsulfate and
      catecholamines at 3-h intervals during wake. These measurements were conducted on
      3 consecutive days 4 times during the two campaigns. Nondominant wrist activity
      and subjective fatigue was monitored throughout both study phases. RESULTS: Daily
      means of activity showed significant differences between the two study conditions
      (with lower values during the 1.2% condition), but these differences only
      occurred during day-time, whereas during sleep activity levels remained the same.
      Diurnal mean and circadian amplitude of the temperature rhythm was also
      significantly lower during the 1.2% condition. CONCLUSIONS: The lower daily mean
      and circadian amplitudes of temperature during the higher CO2 level can be
      explained by lower physical activity that was monitored under this level, i.e., a
      masking effect. We hesitate to explain the lower activity (and hence temperature)
      as a response to the changed CO2 concentration. More probably, subjects became so
      acquainted with the procedures of the study protocol during the second study
      phase (1.2% CO2) that they did not need similar effort to conduct the tasks as
      during the first phase. The activity level during sleep which was the same during
      the two phases may support this conclusions. Thus, we conclude that CO2 levels up
      to 1.2% do not impair the circadian rhythm of healthy men.

PMID- 9591623
TI  - Joint NASA-ESA-DARA Study. Part three: effects of chronically elevated CO2 on
      mental performance during 26 days of confinement.
AB  - BACKGROUND: Short-term exposures to increased CO2 concentrations in breathing air
      up to 5% are assumed to have only negligible behavioral effects. In the present
      study it was examined to what extent prolonged exposures to moderately elevated
      levels of CO2 in the ambient air affect human performance. METHOD: During two
      phases of 26 d of confinement in a diving chamber a group of four subjects was
      exposed to two different levels of CO2 (0.7% and 1.2%). Cognitive, visuo-motor,
      and time-sharing performance were assessed repeatedly before, during, and after
      the exposure by means of a task battery including grammatical reasoning, memory
      search, unstable tracking, and dual tasks. In addition, subjective workload and
      mood ratings were collected. A second group of four subjects served as a control
      group who performed the different tasks on the same 26-d time schedule without
      being exposed to confinement and elevated CO2. RESULTS: During exposure to 0.7%
      CO2 only tracking performance was slightly disturbed compared with baseline
      levels, whereas performance of the control group remained stable. The time course
      of this effect suggested that it was related to chamber adaptation rather than to
      increased levels of CO2. During exposure to 1.2% CO2, tracking performance again
      was significantly impaired. In contrast to the lower exposure condition, the time
      course of this effect appeared to be related to the CO2 load and covaried with a
      loss of subjective alertness. CONCLUSIONS: The study indicates that at least
      visuomotor performance might be affected by CO2 concentrations in the ambient
      atmosphere as small as 1.2% if subjects are chronically exposed to these
      concentrations in a confined environment. The strength of these effects, however,
      does not appear to be of operational relevance.

PMID- 9591624
TI  - Case report: cough syncope in a U.S. Army aviator.
AB  - Syncope is a very common presentation to the primary care provider and the
      emergency room physician. The consequences of syncope while driving can be
      tragic. Likewise the consequences in the flight environment can be devastating.
      This case presents tussive syncope while driving in a 41-yr-old previously
      healthy male aviator. The diagnosis, management, and aeromedical disposition are
      presented.

PMID- 9591625
TI  - Case report: inflight decompression sickness affecting the temporomandibular
      joint.
AB  - A 26-yr-old AC-130 gunner developed unilateral temporomandibular joint (TMJ) pain
      while flying a combat support mission. A diagnosis of decompression sickness
      (DCS) was made based on his symptoms and risk factors that included prolonged
      exposure to high altitude (60 to 90 min at 18,000 ft), cold temperature (-11
      degrees C), and increased inflight activity. His symptoms resolved with 100%
      oxygen and he was returned to flying status after 72 h. Altitude related DCS is
      an unusual occurrence and this is the first reported case of inflight DCS
      affecting the temporomandibular joint.

PMID- 9591626
TI  - Eye injuries from laser exposure: a review.
AB  - Lasers pose a significant threat to vision in modern military operations. Anti
      personnel lasers have been designed that can cause intentional blindness in large
      numbers of personnel. Although the use of blinding laser weapons during combat
      has been prohibited by international legislation, research and development of
      these weapons have not been prohibited, and significant controversy remains.
      Unintentional blinding can also result from other types of lasers used on the
      battlefield, such as range-finders and anti-material lasers. Lasers that are
      capable of producing blindness operate within specific wavelength parameters and
      include visible and near infrared lasers. Patients who suffer from laser eye
      injuries usually complain of flash blindness, followed by transient or permanent
      visual loss. Laser retinal damage should be suspected in any patient with visual
      complaints in an operational setting. The treatment for laser retinal injuries is
      extremely limited, and prevention is essential. Improved protective eyeware and
      other countermeasures to laser eye injury are necessary as long as the threat
      remains.

PMID- 9591627
TI  - Tactical vs. other simulated aerial combat maneuvers.
AB  - BACKGROUND: There is a need for a more operationally relevant +Gz profile for
      centrifuge-based research and evaluation. This article describes a simulated
      aerial combat maneuver (SACM) named the Tactical Aerial Combat Maneuver (TACM).
      HYPOTHESIS: A more representative centrifuge-based SACM can be devised for high-G
      acceleration research and evaluation. METHODS: TACM consists of 9G x 5 s, 5G x 1
      s, 8G x 5 s, and 4G x 2 s. TACM was compared against the widely accepted 4.5-7G
      and 5-9G SACMs. There were 15 centrifuge subjects used in this study. RESULTS:
      TACM accounted for all four incidents of G-Induced Loss of Consciousness (G-LOC);
      and most incidents of blackouts (5 of 8) observed. CONCLUSION: TACM simulates the
      seesaw pattern of +Gz forces of aerial combat and retains the reproducibility
      needed for acceleration research and evaluation. TACM captures the high onset,
      high amplitude +Gz changes of aerial combat when G-LOC and blackouts are more
      likely to occur. TACM should be particularly useful for evaluation of G
      protective equipment and maneuvers, as well as fighter aircrew medical
      evaluations.

PMID- 9591628
TI  - Identification of a 910-kb region of common allelic loss in chromosome bands
      16q24.1-q24.2 in human lung cancer.
AB  - To understand the molecular pathogenesis of human lung cancer, we analyzed
      allelic deletions on the long arm of chromosome 16 by PCR amplification of
      microsatellite markers. A total of 203 lung cancer specimens (78 squamous cell
      carcinomas and 125 adenocarcinomas) were analyzed. In both cell types, a common
      region of allelic loss was identified in 16q24.1-q24.2; it is flanked by the two
      markers D16S534 and D16S422 that spanned at most 910 kb. These results were
      confirmed by fluorescence in situ hybridization. There was no correlation between
      allelic loss and histopathologic diagnosis or clinical stage. These results
      suggest the existence of a tumor-suppressor gene that plays an important role in
      the course of carcinogenesis in both squamous cell carcinoma and adenocarcinoma
      of the lungs.

PMID- 9591629
TI  - Distinct patterns of deletion on 10p and 10q suggest involvement of multiple
      tumor suppressor genes in the development of astrocytic gliomas of different
      malignancy grades.
AB  - Deletions of chromosome 10 are the most frequent genetic abnormality in
      glioblastomas. Several commonly deleted regions have been proposed; however, they
      are not coincident. We have deletion mapped chromosome 10 in 198 astrocytic
      gliomas using 53 microsatellite markers. Two commonly deleted regions on 10p were
      identified, one of which lies between D10S594 and D10S559 and the other between
      D10S1713 and D10S189. Most of 10q deletions were large and included a region
      distal to D10S554. Four glioblastomas of 122 had patterns suggestive of
      homozygous deletions at D10S541, a locus close and distally located to the
      PTEN/MMAC1 gene. Losses of alleles were found not only in glioblastomas (93%) but
      also in anaplastic astrocytomas (66%) and in astrocytomas (35%). Most
      glioblastomas lost one entire chromosome 10, while astrocytomas preferentially
      lost only 10p. The data suggest that a number of tumor suppressor genes on
      chromosome 10, in addition to PTEN/MMAC1, may be associated with astrocytic
      glioma development.

PMID- 9591630
TI  - Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with
      morphologic and clinical features: a report of the CHAMP Study Group. Chromosomes
      and MorPhology.
AB  - With the aim of identifying objective cytogenetic-morphologic correlations, we
      evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as
      malignant fibrous histiocytomas) with clonal chromosome aberrations both
      cytogenetically and morphologically as part of an international collaborative
      study. By detailed histopathologic examination, most cases could be categorized
      into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4
      pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated
      liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4
      myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as
      myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant
      mesenchymoma, 1 as extraskeletal osteosarcoma, I as sarcoma resembling
      proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three-grade
      system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly
      complex karyotypes. A total of 24 recurrent abnormalities (defined by their
      presence in at least five cases) were detected: ring chromosomes, homogeneously
      staining regions (hsr) and/or double minute chromosomes (dmin), and structural
      rearrangement of 22 different chromosome bands or regions. The frequency and
      distribution of the recurrent karyotypic features were uneven. Grade 3 tumors
      displayed, on average, more aberrations per case than did grade 2 tumors. Nine of
      the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and
      19q13, were found only among the high-grade tumors. When the tumors were
      subdivided according to lineage of differentiation, the highest frequency of
      aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas,
      myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements
      was, however, specific for any of these subgroups. The sole consistent
      cytogenetic-morphologic association was that all three dedifferentiated
      liposarcomas had multiple abnormal clones, at least one of which contained
      supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore
      seems unlikely that cytogenetic analysis can assist in the differential
      diagnostic subclassification of pleomorphic sarcomas, nor was there any clear-cut
      indication that the karyotypic picture could be used to predict clinical outcome.
      Although the mean number of recurrent chromosome aberrations was almost twice as
      high in sarcomas that gave rise to metastases as among those that did not, no
      particular aberration was restricted to either of the two subgroups.

PMID- 9591631
TI  - A widely expressed transcription factor with multiple DNA sequence specificity,
      CTCF, is localized at chromosome segment 16q22.1 within one of the smallest
      regions of overlap for common deletions in breast and prostate cancers.
AB  - The cellular protooncogene MYC encodes a nuclear transcription factor that is
      involved in regulating important cellular functions, including cell cycle
      progression, differentiation, and apoptosis. Dysregulated MYC expression appears
      critical to the development of various types of malignancies, and thus factors
      involved in regulating MYC expression may also play a key role in the
      pathogenesis of certain cancers. We have cloned one such MYC regulatory factor,
      termed CTCF, which is a highly evolutionarily conserved-11-zinc finger
      transcriptional factor possessing multiple DNA sequence specificity. CTCF binds
      to a number of important regulatory regions within the 5' noncoding sequence of
      the human MYC oncogene, and it can regulate its transcription in several
      experimental systems. CTCF mRNA is expressed in cells of multiple different
      lineages. Enforced ectopic expression of CTCF inhibits cell growth in culture.
      Southern blot analyses and fluorescence in situ hybridization (FISH) with normal
      human metaphase chromosomes showed that the human CTCF is a single-copy gene
      situated at chromosome locus 16q22. Cytogenetic studies have pointed out that
      chromosome abnormalities (deletions) at this locus frequently occur in many
      different human malignancies, suggesting the presence of one or more tumor
      suppressor genes in the region. To narrow down their localization, several loss
      of heterozygosity (LOH) studies of chromosome arm 16q in sporadic breast and
      prostate cancers have been carried out to define the most recurrent and smallest
      region(s) of overlap (SRO) for commonly deleted chromosome arm 16q material. For
      CTCF to be considered as a candidate tumor suppressor gene associated with
      tumorigenesis, it should localize within one of the SROs at 16q. Fine-mapping of
      CTCF has enabled us to assign the CTCF gene to about a 2 centiMorgan (cM)
      interval of 16q22.1 between the somatic cell hybrid breakpoints CY130(D) and CY4,
      which is between markers D16S186 (16AC16-101) and D16S496 (AFM214zg5). This
      relatively small region, containing the CTCF gene, overlaps the most frequently
      observed SROs for common chromosomal deletions found in sporadic breast and
      prostate tumors. In one of four analyzed paired DNA samples from primary breast
      cancer patients, we have detected a tumor-specific rearrangement of CTCF exons
      encoding the 11-zinc-finger domain. Therefore, taken together with other CTCF
      properties, localization of CTCF to a narrow cancer-associated chromosome region
      suggests that CTCF is a novel candidate tumor suppressor gene at 16q22.1.

PMID- 9591632
TI  - A beta-catenin mutation in a sporadic colorectal tumor of the RER phenotype and
      absence of beta-catenin germline mutations in FAP patients.
AB  - As a signaling protein in the Wnt pathway beta-catenin plays a crucial role in
      the regulation of cellular proliferation. Recently, oncogenic beta-catenin
      mutations were described in human colorectal cancer and melanoma cell lines.
      Since activating mutations in the beta-catenin gene have similar effects on the
      biochemical level as inactivating mutations in the tumor suppressor gene APC, it
      is speculated that beta-catenin mutations may substitute APC gene inactivation in
      carcinogenesis. To address this question we analyzed twenty-three sporadic
      colorectal tumors of different progression states for mutations in the beta
      catenin gene. Eighteen of these tumors showed the wildtype APC gene sequence. In
      only one of the tumors with wildtype APC a beta-catenin gene mutation was found.
      This tumor was of the RER (replication error) phenotype which may explain the
      finding that the mutation occurred in a sequential repeat motif of the beta
      catenin gene. The second aim of this study was to investigate whether differences
      in the phenotypic variability in FAP (familial adenomatous polyposis coli) might
      be due to inherited alterations in the beta-catenin gene. For this we analyzed
      DNA from fourteen FAP patients from eight different families for germline
      mutations in the beta-catenin gene. We did not find any beta-catenin gene
      alteration in these samples. Our results indicate that somatic beta-catenin
      activating mutations contribute only to a minor part of human colorectal tumors
      and that germline beta-catenin mutations do not play a role in the variability of
      symptoms in FAP.

PMID- 9591633
TI  - Human neuroblastoma demonstrating clonal evolution in vivo.
AB  - Neuroblastoma demonstrates various clinical behaviors, ranging from spontaneous
      regression to rapid progression regardless of the therapy used. To study the
      possibility that progression occurs in neuroblastoma through the accumulation of
      genetic aberrations, we analyzed the clonal constitution of the primary tumor and
      metastatic tumor samples from a stage-4 patient. Using cytofluorometry and FISH
      analyses, intratumor clonal heterogeneity was revealed. In the initial primary
      tumor sample, the nuclear DNA content indicated the coexistence of diploid and
      aneuploid clones, and the copy number of chromosome 1 varied from two to six. The
      chromosome 1 aneusomy population was composed of MYCN-amplified and 1p-deleted
      clones, whereas, in the chromosome 1 disomy population, coexistence of MYCN
      amplified and non-amplified clones as well as 1p-deleted and 1p-intact clones was
      revealed. In the primary tumor after chemotherapy, the DNA-diploid component had
      become predominant, although the coexistence of MYCN-amplified and non-amplified
      clones could still be demonstrated in poorly- and well-differentiated tumor
      regions, respectively. This contrasted with the findings in the metastatic
      tumors, in which either diploid or aneuploid clone with MYCN amplification and 1p
      deletion dominated completely in each metastatic site. The findings suggest that
      the aneuploid clones had evolved from a diploid clone with MYCN amplification and
      a 1p deletion which, in turn, may have evolved from a diploid clone with neither
      MYCN nor 1p abnormality. This illustrates how various stages of multiple-step
      tumorigenesis may provide clues to a better understanding of the clinical
      heterogeneity of neuroblastoma.

PMID- 9591634
TI  - Comparative genomic hybridization analysis of sporadic neuroendocrine tumors of
      the digestive system.
AB  - Little information is available on the molecular mechanisms underlying
      neuroendocrine tumorigenesis. To obtain an overview of the genomic imbalances
      characterizing these tumors, we studied 20 benign or malignant sporadic endocrine
      gastroenteropancreatic tumors by comparative genomic hybridization. Chromosomal
      imbalances were found in all tumors. Gains of chromosomal material were more
      frequent than losses. The most frequent gains were of chromosomes and chromosome
      arms 5 (55%), 14 (55%), 17q (55%), and 7 (50%). Losses were most frequent from
      11q (30%) and 16p (30%). Gains of chromosome 5 did not occur in nonmetastatic
      tumors, whereas losses of 9p were observed exclusively in intestinal tumors. In
      addition, we found two high-level amplifications, of 17q11-21 and 19q13. A
      complementary FISH analysis revealed that the gain in 17q11-21 included
      amplification of the protooncogene HER2/neu. As in multiple endocrine neoplasia
      type-1-associated tumors, deletions of chromosome band 11q13 appear to be
      involved in the development of sporadic digestive tract neuroendocrine tumors,
      but our results suggest that other chromosomal regions are also involved.

PMID- 9591635
TI  - Cervical intraepithelial neoplasia III shows frequent allelic loss in 3p and 6p.
AB  - We have shown previously that a significant number of invasive cervical cancers
      (ICC) have nonrandom chromosomal losses in 3p, 6p, 11q, 2q, 6q, and 19q, thereby
      suggesting that genes involved in the suppression of tumor development or
      progression are located in these regions. Cervical intraepithelial neoplasia
      (CIN) III is considered the precursor lesion for ICC of squamous type and occurs
      frequently with ICC of glandular type. In an effort to define which chromosomal
      losses are present in the precursor lesions, we identified CIN III lesions from
      24 ICC treated by radical hysterectomy. Thirty-three CIN III associated with 22
      squamous carcinomas and 2 adenocarcinomas were carefully microdissected from the
      paraffin-embedded sections. The whole genomic DNA from CIN III was amplified with
      short random primers. DNA from ICC, CIN III, and normal tissue was analyzed at
      the six chromosomal regions with polymorphic markers. Thirty-eight percent of
      hysterectomy specimens had loss of heterozygosity (LOH) in at least one of the
      CIN III lesions from each case. Loss occurred in 30% of cases in 3p14.1-12 (37%
      for associated ICC), 21% in 6p23 (33%), 14% in 2q33-37 (27%), 0 in 11q23.3 (33%),
      4% in 19q13.4 (13%), and 0 in 6q21-23.3 (18%). These results suggest that
      mutations in 3p and 6p are important early in tumorigenesis, whereas 11q and 6q
      contain genes important later in tumor progression. Invasive and preinvasive
      cervical lesions appear to develop from multifocal genetic events since
      consistent losses do not occur within all precursor lesions in the same patient.

PMID- 9591636
TI  - Mechanism of cyclin D1 (CCND1, PRAD1) overexpression in human cancer cells:
      analysis of allele-specific expression.
AB  - The cyclin D1/CCND1 oncogene (PRAD1) is amplified in 15% of primary human breast
      cancers and overexpressed in 30-50% of breast cancers, suggesting that mechanisms
      in addition to DNA amplification may lead to deregulated expression of this gene
      in breast cancer. Cyclin D1 overexpression at a higher frequency than gene
      amplification is also seen in a variety of other tumors. Cyclin D1 overexpression
      without amplification could result from a trans-acting regulatory disturbance or
      could be a consequence of a clonal regulatory mutation in one allele of the gene.
      We have, therefore, examined whether the overexpression of cyclin D1 mRNA is
      derived from one parental allele or both alleles in tumor cell lines with or
      without amplification of the cyclin D1 gene. Eight tumor cell lines, MCF-7, SK-BR
      3, ZR-75-1, U-2-OS, SK-LMS-1, DLD1, HCT15, and HT29, out of 20 tumor cells
      initially examined were found to be heterozygous at the polymorphic NciI site
      within exon 4 of the cyclin D1 gene. Polymerase chain reaction and NciI digestion
      (PCR-RFLP) analysis of genomic DNA demonstrated DNA amplification of one allele
      in the ZR-75-1 cells and HT29 cells and no such imbalance in cyclin D1 gene copy
      number in the other cells, consistent with Southern blot analyses. Reverse
      transcription polymerase chain reaction analysis and NciI digestion (RT-PCR-RFLP)
      of total cDNA revealed that the overexpressed cyclin D1 mRNA is preferentially
      derived from the amplified allele in the ZR-75-1 and HT29 cells. In contrast, the
      other tumor cells overexpressed cyclin D1 mRNA equally from both alleles. This
      finding strongly suggests that, in breast, sarcoma, and in colon cancer cells
      with cyclin D1 overexpression and normal gene copy number, elevated levels of
      cyclin D1 mRNA result from a trans-acting influence on both alleles rather than a
      clonal somatic mutation or rearrangement in or near a single cyclin D1 gene.

PMID- 9591637
TI  - Codeletion of CDKN2 and MTAP genes in a subset of non-Hodgkin's lymphoma may be
      associated with histologic transformation from low-grade to diffuse large-cell
      lymphoma.
AB  - Identifying the various genetic alterations that contribute to lymphomagenesis is
      key to our improved understanding of the biological behavior of the disease.
      Recently, we and others have defined a tumor suppressor region on the short arm
      of chromosome 9 harboring a cluster of genes, including MTAP, CDKN2A (p16INK4a),
      and CDKN2B (p15INK4B), which is frequently deleted in a variety of tumor types.
      To determine whether this region is involved in a particular subset of malignant
      lymphomas, we have examined 16 cases of diffuse large-cell lymphoma (DLCL)
      (including three cases that evolved from low-grade non-Hodgkin lymphoma (NHL)
      (transformed DLCL)), and nine cases of low-grade NHL that had subpopulations of
      large cells with a diffuse growth pattern (seven follicular NHL, one chronic
      lymphocytic leukemia, one mycosis fungoides). Interphase fluorescence in situ
      hybridization was performed on these samples using a 250-kb cosmid contig
      (COSp16), which encompasses MTAP, CDKN2A, and CDKN2B. Six of the 16 DLCLs and one
      of nine low-grade NHLs had deletions of COSp16. COSp16 was homozygously deleted
      in four cases; two cases had hemizygous deletions, and one case had a partial
      homozygous deletion of the cosmid contig. Three of 13 cases of de novo DLCL, all
      three transformed DLCLs, and one of nine low-grade NHL had COSp16 deletions.
      Although the numbers are small, COSp16 deletion was associated with transformed
      DLCL in contrast to de novo DLCL (P < 0.04, Fisher's exact test) or low-grade NHL
      (P < 0.02). The COSp16 deletion was mostly submicroscopic and was not observed in
      association with any specific recurring cytogenetic abnormalities. These results
      suggest that targeted deletion of the CDKN2A region occurs in a subset of non
      Hodgkin's lymphomas, and may be associated with transformed lymphomas.

PMID- 9591638
TI  - DNA gains in 3q occur frequently in squamous cell carcinoma of the lung, but not
      in adenocarcinoma.
AB  - We performed a comparative genomic hybridization study on 25 samples of
      adenocarcinoma and 19 samples of squamous cell carcinoma of the lung to detect
      recurrent changes in the genetic material. DNA copy number changes were found in
      16 squamous cell carcinoma samples and 17 adenocarcinoma samples. The most common
      changes were gains of DNA sequences in 3q (43%), 1q (34%), 8q (32%), 5p, (30%),
      7p (25%), and 12p (25%). Of the squamous cell carcinoma samples with DNA copy
      number changes, 94% (15/16) had a gain in 3q (minimal common region of overlap
      q24-qter), whereas only 24% (4/17) of the adenocarcinoma samples with DNA copy
      number changes showed a gain in 3q (q22-qter) (P < 0.001). Six high-level
      amplifications in 3q (q26.2-q26.3) were detected in the squamous cell carcinoma
      samples but none were observed in the adenocarcinoma samples. Our results suggest
      that amplification of genes in 3q may be important in the tumorigenesis of
      squamous cell carcinoma but not necessarily of adenocarcinoma.

PMID- 9591639
TI  - Expression of heavy-chain constant region of immunoglobulin and T-cell receptor
      gene transcripts in human non-hematopoietic tumor cell lines.
AB  - Expression of gene transcripts for immunoglobulins and a T-cell receptor was
      investigated in non-hematopoietic tumor cell lines using the highly sensitive RT
      nested PCR method. These proteins are reported to be produced and secreted or
      expressed in malignancies originating from hematopoietic organs only. Originally
      designed PCR primers for different exons coding for the heavy-chain constant
      regions of IgM, IgD, IgG3, IgG1, IgE, and IgA and the T-cell receptor-alpha were
      used. All gene transcripts were detected in the 5 investigated cancer cell lines
      without exception. The results suggest that even non-hematopoietic cancer cells
      transcribe immunoglobulin and T-cell receptor genes and may produce the
      corresponding proteins.

PMID- 9591640
TI  - Expanding time scales usher in a new era for kinetic studies.

PMID- 9591641
TI  - Identification of the ice-binding surface on a type III antifreeze protein with a
      "flatness function" algorithm.
AB  - Antifreeze proteins (AFPs) adsorb to surfaces of growing ice crystals, thereby
      arresting their growth. The prevailing hypothesis explains the nature of
      adsorption in terms of a match between the hydrophilic side chains on the AFP's
      ice-binding surface (IBS) and the water molecules on the ice surface. The number
      and spatial arrangement of hydrogen bonds thus formed have been proposed to
      account, respectively, for the binding affinity and specificity. The crystal
      structure of a type III AFP from ocean pout (isoform HPLC-3) has been determined
      to 2.0-A resolution. The structure reveals an internal dyad motif formed by two
      19-residue, loop-shaped elements. Based on of the flatness observed on the type I
      alpha-helical AFP's IBS, an automated algorithm was developed to analyze the
      surface planarity of the globular type III AFP and was used to identify the IBS
      on this protein. The surface with the highest flatness score is formed by one
      loop of the dyad motif and is identical to the IBS deduced from earlier
      mutagenesis studies. Interestingly, 67% of this surface contains nonpolar solvent
      accessible surface area. The success of our approach to identifying the IBS on an
      AFP, without considering the presence of polar side chains, indicates that
      flatness is the first approximation of an IBS. We further propose that the
      specificity of interactions between an IBS and a particular ice-crystallographic
      plane arises from surface complementarity.

PMID- 9591642
TI  - The importance of electric field distribution for effective in vivo
      electroporation of tissues.
AB  - Cells exposed to short and intense electric pulses become permeable to a number
      of various ionic molecules. This phenomenon was termed electroporation or
      electropermeabilization and is widely used for in vitro drug delivery into the
      cells and gene transfection. Tissues can also be permeabilized. These new
      approaches based on electroporation are used for cancer treatment, i.e.,
      electrochemotherapy, and in vivo gene transfection. In vivo electroporation is
      thus gaining even wider interest. However, electrode geometry and distribution
      were not yet adequately addressed. Most of the electrodes used so far were
      determined empirically. In our study we 1) designed two electrode sets that
      produce notably different distribution of electric field in tumor, 2)
      qualitatively evaluated current density distribution for both electrode sets by
      means of magnetic resonance current density imaging, 3) used three-dimensional
      finite element model to calculate values of electric field for both electrode
      sets, and 4) demonstrated the difference in electrochemotherapy effectiveness in
      mouse tumor model between the two electrode sets. The results of our study
      clearly demonstrate that numerical model is reliable and can be very useful in
      the additional search for electrodes that would make electrochemotherapy and in
      vivo electroporation in general more efficient. Our study also shows that better
      coverage of tumors with sufficiently high electric field is necessary for
      improved effectiveness of electrochemotherapy.

PMID- 9591643
TI  - A novel crystallization method for visualizing the membrane localization of
      potassium channels.
AB  - The high permeability of K+ channels to monovalent thallium (Tl+) ions and the
      low solubility of thallium bromide salt were used to develop a simple yet very
      sensitive approach to the study of membrane localization of potassium channels.
      K+ channels (Kir1.1, Kir2.1, Kir2.3, Kv2.1), were expressed in Xenopus oocytes
      and loaded with Br ions by microinjection. Oocytes were then exposed to
      extracellular thallium. Under conditions favoring influx of Tl+ ions (negative
      membrane potential under voltage clamp, or high concentration of extracellular
      Tl+), crystals of TlBr, visible under low-power microscopy, formed under the
      membrane in places of high density of K+ channels. Crystals were not formed in
      uninjected oocytes, but were formed in oocytes expressing as little as 5 microS
      K+ conductance. The number of observed crystals was much lower than the estimated
      number of functional channels. Based on the pattern of crystal formation, K+
      channels appear to be expressed mostly around the point of cRNA injection when
      injected either into the animal or vegetal hemisphere. In addition to this
      pseudopolarized distribution of K+ channels due to localized microinjection of
      cRNA, a naturally polarized (animal/vegetal side) distribution of K+ channels was
      also frequently observed when K+ channel cRNA was injected at the equator. A
      second novel "agarose-hemiclamp" technique was developed to permit direct
      measurements of K+ currents from different hemispheres of oocytes under two
      microelectrode voltage clamp. This technique, together with direct patch-clamping
      of patches of membrane in regions of high crystal density, confirmed that the
      localization of TlBr crystals corresponded to the localization of functional K+
      channels and suggested a clustered organization of functional channels. With
      appropriate permeant ion/counterion pairs, this approach may be applicable to the
      visualization of the membrane distribution of any functional ion channel.

PMID- 9591645
TI  - Domains in cell plasma membranes investigated by near-field scanning optical
      microscopy.
AB  - Near-field scanning optical microscopy (NSOM) uses the near-field interaction of
      light from a sharp fiber-optic probe with a sample of interest to image surfaces
      at a resolution beyond the diffraction limit of conventional optics. We used NSOM
      to image fluorescently labeled plasma membranes of fixed human skin fibroblasts,
      either dried or in buffer. A patchy distribution of a fluorescent lipid analog
      suggestive of lipid domains was observed in the fixed, dried cells. The sizes of
      these patches were consistent with the sizes of domains implied by fluorescence
      photobleaching recovery measurements. Patches of fluorescent lipid analog were
      not spatially correlated with patches of transmembrane proteins, HLA class I
      molecules labeled with fluorescent antibody; the patchiness of the HLA class I
      molecules was on a smaller scale and was not localized to the same regions of
      membrane as the lipid analog. Sizes of HLA patches were deduced from a two
      dimensional spatial autocorrelation analysis of NSOM images that resolved patches
      with radii of approximately 70 and approximately 600 nm on fixed, dried cells
      labeled with IgG and 300-600 nm on cells labeled with Fab and imaged in buffer.
      The large-size patches were also resolved by far-field microscopy. Both the
      spatial autocorrelation analysis and estimates from fluorescence intensity
      indicate that the small patches seen on fixed, dried cells contain approximately
      25-125 HLA-I molecules each.

PMID- 9591644
TI  - Structure of the erythrocyte membrane skeleton as observed by atomic force
      microscopy.
AB  - The structure of the membrane skeleton on the cytoplasmic surface of the
      erythrocyte plasma membrane was observed in dried human erythrocyte ghosts by
      atomic force microscopy (AFM), taking advantage of its high sensitivity to small
      height variations in surfaces. The majority of the membrane skeleton can be
      imaged, even on the extracellular surface of the membrane. Various fixation and
      drying methods were examined for preparation of ghost membrane samples for AFM
      observation, and it was found that freeze-drying (freezing by rapid immersion in
      a cryogen) of unfixed specimens was a fast and simple way to obtain consistently
      good results for observation without removing the membrane or extending the
      membrane skeleton. Observation of the membrane skeleton at the external surface
      of the cell was possible mainly because the bilayer portion of the membrane sank
      into the cell during the drying process. The average mesh size of the spectrin
      network observed at the extracellular and cytoplasmic surfaces of the plasma
      membrane was 4800 and 3000 nm2, respectively, which indicates that spectrin forms
      a three-dimensionally folded meshwork, and that 80% of spectrin can be observed
      at the extracellular surface of the plasma membrane.

PMID- 9591646
TI  - Progressive DNA bending is made possible by gradual changes in the torsion angle
      of the glycosyl bond.
AB  - Structural comparisons have led to the suggestion that the conformational
      rearrangement that would be required to change A-DNA into the TA-DNA form of DNA
      observed in the complex with the TATA box binding protein (TBP) could be
      completed by modifying only the value of the glycosyl bond chi by approximately
      45 degrees. The lack of a high number of crystal structures of this type makes it
      difficult to conclude whether a smooth transition from A-DNA to TA-DNA can occur
      without disrupting at any point either the Watson-Crick base pairing or the A-DNA
      conformation of the backbone. To explore the possibility of such a smooth
      transition, constrained molecular dynamics simulations were carried out for the
      double-stranded dodecamer d(GGTATATAAAAC), in which a transition from A-DNA to TA
      DNA was induced by modifying only the chi angle values. The results demonstrate
      the feasibility of a continuous path in the A-DNA to TA-DNA transition. Varying
      extents of DNA curvature are also attainable, by maintaining the A-DNA backbone
      structure and Watson-Crick hydrogen bonding while changing the chi angle value
      smoothly from that in A-DNA to one corresponding to B-DNA.

PMID- 9591647
TI  - Atomic force microscopy of crystalline insulins: the influence of sequence
      variation on crystallization and interfacial structure.
AB  - The self-association of proteins is influenced by amino acid sequence, molecular
      conformation, and the presence of molecular additives. In the presence of
      phenolic additives, LysB28ProB29 insulin, in which the C-terminal prolyl and
      lysyl residues of wild-type human insulin have been inverted, can be crystallized
      into forms resembling those of wild-type insulins in which the protein exists as
      zinc-complexed hexamers organized into well-defined layers. We describe herein
      tapping-mode atomic force microscopy (TMAFM) studies of single crystals of
      rhombohedral (R3) LysB28ProB29 that reveal the influence of sequence variation on
      hexamer-hexamer association at the surface of actively growing crystals.
      Molecular scale lattice images of these crystals were acquired in situ under
      growth conditions, enabling simultaneous identification of the rhombohedral
      LysB28ProB29 crystal form, its orientation, and its dynamic growth
      characteristics. The ability to obtain crystallographic parameters on multiple
      crystal faces with TMAFM confirmed that bovine and porcine insulins grown under
      these conditions crystallized into the same space group as LysB28ProB29 (R3),
      enabling direct comparison of crystal growth behavior and the influence of
      sequence variation. Real-time TMAFM revealed hexamer vacancies on the (001)
      terraces of LysB28ProB29, and more rounded dislocation noses and larger terrace
      widths for actively growing screw dislocations compared to wild-type bovine and
      porcine insulin crystals under identical conditions. This behavior is consistent
      with weaker interhexamer attachment energies for LysB28ProB29 at active growth
      sites. Comparison of the single crystal x-ray structures of wild-type insulins
      and LysB28ProB29 suggests that differences in protein conformation at the hexamer
      hexamer interface and accompanying changes in interhexamer bonding are
      responsible for this behavior. These studies demonstrate that subtle changes in
      molecular conformation due to a single sequence inversion in a region critical
      for insulin self-association can have a significant effect on the crystallization
      of proteins.

PMID- 9591648
TI  - Temporally and spectrally resolved imaging microscopy of lanthanide chelates.
AB  - The combination of temporal and spectral resolution in fluorescence microscopy
      based on long-lived luminescent labels offers a dramatic increase in contrast and
      probe selectivity due to the suppression of scattered light and short-lived
      autofluorescence. We describe various configurations of a fluorescence microscope
      integrating spectral and microsecond temporal resolution with conventional
      digital imaging based on CCD cameras. The high-power, broad spectral distribution
      and microsecond time resolution provided by microsecond xenon flashlamps offers
      increased luminosity with recently developed fluorophores with lifetimes in the
      submicrosecond to microsecond range. On the detection side, a gated microchannel
      plate intensifier provides the required time resolution and amplification of the
      signal. Spectral resolution is achieved with a dual grating stigmatic
      spectrograph and has been applied to the analysis of luminescent markers of
      cytochemical specimens in situ and of very small volume elements in
      microchambers. The additional introduction of polarization optics enables the
      determination of emission polarization; this parameter reflects molecular
      orientation and rotational mobility and, consequently, the nature of the
      microenvironment. The dual spectral and temporal resolution modes of acquisition
      complemented by a posteriori image analysis gated on the spatial, spectral, and
      temporal dimensions lead to a very flexible and versatile tool. We have used a
      newly developed lanthanide chelate, Eu-DTPA-cs124, to demonstrate these
      capabilities. Such compounds are good labels for time-resolved imaging microscopy
      and for the estimation of molecular proximity in the microscope by fluorescence
      (luminescence) resonance energy transfer and of molecular rotation via
      fluorescence depolarization. We describe the spectral distribution, polarization
      states, and excited-state lifetimes of the lanthanide chelate crystals imaged in
      the microscope.

PMID- 9591649
TI  - Direct observation of ligand colocalization on individual receptor molecules.
AB  - We have exploited the novel methodology of far-field fluorescence microscopy at
      the single molecule level to study colocalization of two different ligand
      molecules on an individual receptor. The use of dual-wavelength single molecule
      imaging allows discrimination between isolated and colocalized ligands with an
      accuracy of 40 nm. In the case of very close proximity of the two ligands, below
      7 nm, single pair Forster energy-transfer was observed. The latter finding
      unequivocally demonstrates colocalization of two ligands on an individual
      receptor.

PMID- 9591650
TI  - Viscoelastic properties of living embryonic tissues: a quantitative study.
AB  - A number of properties of certain living embryonic tissues can be explained by
      considering them as liquids. Tissue fragments left in a shaker bath round up to
      form spherical aggregates, as do liquid drops. When cells comprising two distinct
      embryonic tissues are mixed, typically a nucleation-like process takes place, and
      one tissue sorts out from the other. The equilibrium configurations at the end of
      such sorting out phenomena have been interpreted in terms of tissue surface
      tensions arising from the adhesive interactions between individual cells. In the
      present study we go beyond these equilibrium properties and study the
      viscoelastic behavior of a number of living embryonic tissues. Using a
      specifically designed apparatus, spherical cell aggregates are mechanically
      compressed and their viscoelastic response is followed. A generalized Kelvin
      model of viscoelasticity accurately describes the measured relaxation curves for
      each of the four tissues studied. Quantitative results are obtained for the
      characteristic relaxation times and elastic and viscous parameters. Our analysis
      demonstrates that the cell aggregates studied here, when subjected to mechanical
      deformations, relax as elastic materials on short time scales and as viscous
      liquids on long time scales.

PMID- 9591651
TI  - Far-field analysis of coupled bulk and boundary layer diffusion toward an ion
      channel entrance.
AB  - We present a far-field analysis of ion diffusion toward a channel embedded in a
      membrane with a fixed charge density. The Smoluchowski equation, which represents
      the 3D problem, is approximated by a system of coupled three- and two-dimensional
      diffusions. The 2D diffusion models the quasi-two-dimensional diffusion of ions
      in a boundary layer in which the electrical potential interaction with the
      membrane surface charge is important. The 3D diffusion models ion transport in
      the bulk region outside the boundary layer. Analytical expressions for
      concentration and flux are developed that are accurate far from the channel
      entrance. These provide boundary conditions for a numerical solution of the
      problem. Our results are used to calculate far-field ion flows corresponding to
      experiments of Bell and Miller (Biophys. J. 45:279, 1984).

PMID- 9591652
TI  - Nucleic acid vibrational circular dichroism, absorption, and linear dichroism
      spectra. II. A DeVoe theory approach.
AB  - The DeVoe polarizability theory is used to calculate vibrational circular
      dichroism (VCD) and infrared (IR) absorption spectra of four polyribonucleotides:
      poly(rA) x poly(rU), poly(rU) x poly(rA) x poly(rU), poly(rG) x poly(rC), and
      poly(rC+) x poly(rI) x poly(rC). This is the first report on the use of the DeVoe
      theory to calculate VCD, oriented VCD, IR absorption, and IR linear dichroism
      (LD) spectra of double- and triple-stranded polyribonucleotides. Results are
      reported for DeVoe theory calculations--within the base-stretching 1750-1550 cm(
      1) spectral region--on several proposed multistranded polyribonucleotide
      geometries. The calculated spectra obtained from these proposed geometries are
      compared with previously reported measured and calculated VCD and IR spectral
      results. Base-base hydrogen-bonding effects on the frequencies and magnitudes of
      the base carbonyl stretching modes are explicitly considered. The good agreements
      found between calculated and measured spectra are proposed to be further evidence
      of the usefulness of the DeVoe theory in drawing three-dimensional structural
      conclusions from measured polyribonucleotide VCD and IR spectra.

PMID- 9591653
TI  - A model for diffusive transport through a spherical interface probed by pulsed
      field gradient NMR.
AB  - In biological systems, because of higher intracellular viscosity and/or the
      restriction of the diffusion space inside cells, the (apparent) diffusion
      coefficient of an intracellular species (e.g., water) is generally smaller than
      when it is in the extracellular medium. This difference affects the spin-echo
      signal attenuation in the pulsed field gradient NMR experiment and thus affords a
      means of separating the intracellular from the extracellular species, thereby
      providing a basis for studying transmembrane transport. Such experiments have
      commonly been analyzed using the macroscopic model of Karger (see Adv. Magn.
      Reson. 21:1-89 (1988)). In our previous study, we considered a microscopic model
      of diffusive transport through a spherical interface using the short gradient
      pulse approximation (J. Magn. Reson. A114:39-46 (1995)). The spins in the
      external medium were modeled with the "partially absorbing wall" condition or as
      having a small but finite lifetime. In the present paper, we extend our treatment
      to the case in which there is no limitation upon the lifetime in either medium.
      We also consider a simple modification of Karger's model that more properly
      accounts for the restricted intracellular diffusion. Importantly, it was found
      that the exact solution within the short gradient pulse approximation developed
      here and the modified Karger model are in close agreement in the (experimentally
      relevant) long-time limit. The results of this study show that when there is no
      limitation upon the lifetime of the transported species in either phase, the spin
      echo attenuation curve is very sensitive to transport.

PMID- 9591654
TI  - Spatial sensing of stimulus gradients can be superior to temporal sensing for
      free-swimming bacteria.
AB  - Predictions of the minimal size an organism must have to swim along stimulus
      gradients were used to compare the relative advantages of sensory systems
      employing spatial (simultaneous) and temporal (sequential) gradient detection
      mechanisms for small free-swimming bacteria, leading to the following
      conclusions: 1) there are environmental conditions where spatial detection
      mechanisms can function for smaller organisms than can temporal mechanisms, 2)
      temporal mechanisms are superior (have a smaller size limit) for the difficult
      conditions of low concentration and shallow gradients, but 3) observed bacterial
      chemotaxis occurs mostly under conditions where spatial mechanisms have a smaller
      size limit, and 4) relevant conditions in the natural environment favor temporal
      mechanisms in some cases and spatial mechanisms in others. Thus, sensory ecology
      considerations do not preclude free-swimming bacteria from employing spatial
      detection mechanisms, as has been thought, and microbiologists should be on the
      lookout for them. If spatial mechanisms do not occur, the explanation should be
      sought elsewhere.

PMID- 9591656
TI  - Fast transient currents in Na,K-ATPase induced by ATP concentration jumps from
      the P3-[1-(3',5'-dimethoxyphenyl)-2-phenyl-2-oxo]ethyl ester of ATP.
AB  - Electrogenic ion transport by Na,K-ATPase was investigated by analysis of
      transient currents in a model system of protein-containing membrane fragments
      adsorbed to planar lipid bilayers. Sodium transport was triggered by ATP
      concentration jumps in which ATP was released from an inactive precursor by an
      intense near-UV light flash. The method has been used previously with the P3-1-(2
      nitrophenyl)ethyl ester of ATP (NPE-caged ATP), from which the relatively slow
      rate of ATP release limits analysis of processes in the pump mechanism controlled
      by rate constants greater than 100 s(-1) at physiological pH. Here Na,K-ATPase
      was reinvestigated using the P3-[1-(3,5-dimethoxyphenyl)-2-phenyl-2-oxo]ethyl
      ester of ATP (DMB-caged ATP), which has an ATP release rate of >10(5) s(-1).
      Under otherwise identical conditions, photorelease of ATP from DMB-caged ATP
      showed faster kinetics of the transient current compared to that from NPE-caged
      ATP. With DMB-caged ATP, transient currents had rate profiles that were
      relatively insensitive to pH and the concentration of caged compound. Rate
      constants of ATP binding and of the E1 to E2 conformational change were
      compatible with earlier studies. Rate constants of enzyme phosphorylation and ADP
      dependent dephosphorylation were 600 s(-1) and 1.5 x 10(6) M(-1) s(-1),
      respectively, at pH 7.2 and 22 degrees C.

PMID- 9591655
TI  - Surface charge and lanthanum block of calcium current in bullfrog sympathetic
      neurons.
AB  - The density of surface charge associated with the calcium channel pore was
      estimated from the effect of extracellular ionic strength on block by La3+.
      Currents carried by 2 mM Ba2+ were recorded from isolated frog sympathetic
      neurons by the whole-cell patch-clamp technique. In normal ionic strength (120 mM
      N-methyl-D-glucamine, NMG), La3+ blocked the current with high affinity (IC50 =
      22 nM at 0 mV). La3+ block was relieved by strong depolarization in a time- and
      voltage-dependent manner. After unblocking, open channels reblocked rapidly at 0
      mV, allowing estimation of association and dissociation rates for La3+: k(on) =
      (7.2 +/- 0.7) x 10(8) M(-1) s(-1), k(off) = 10.0 +/- 0.5 s(-1). To assess surface
      charge effects, La3+ block was also measured in low ionic strength (12.5 mM NMG)
      and high ionic strength (250 mM NMG). La3+ block was higher affinity and faster
      by two- to threefold in 12.5 mM NMG, with little effect of 250 mM NMG. The data
      could be described by Gouy-Chapman theory with a surface charge density of
      approximately 1 e-/3000-4000 A2. These results indicate that there is a small but
      detectable surface charge associated with the pore of voltage-dependent calcium
      channels.

PMID- 9591657
TI  - Gating of I(sK) channels expressed in Xenopus oocytes.
AB  - The channel underlying the slow component of the voltage-dependent delayed
      outward rectifier K+ current, I(Ks), in heart is composed of the minK and KvLQT1
      proteins. Expression of the minK protein in Xenopus oocytes results in I(Ks)-like
      currents, I(sK), due to coassembly with the endogenous XKvLQT1. The kinetics and
      voltage-dependent characteristics of I(sK) suggest a distinct mechanism for
      voltage-dependent gating. Currents recorded at 40 mV from holding potentials
      between -60 and -120 mV showed an unusual "cross-over," with the currents
      obtained from more depolarized holding potentials activating more slowly and
      deviating from the Cole-Moore prediction. Analysis of the current traces revealed
      two components with fast and slow kinetics that were not affected by the holding
      potential. Rather, the relative contribution of the fast component decreased with
      depolarized holding potentials. Deactivation and reactivation, after a short
      period of repolarization (100 ms), was markedly faster than the fast component of
      activation. These gating properties suggest a physiological mechanism by which
      cardiac I(Ks) may suppress premature action potentials.

PMID- 9591658
TI  - Sensitivity to voltage-independent inhibition determined by pore-lining region of
      the acetylcholine receptor.
AB  - Some noncompetitive inhibitors (e.g., ganglionic blockers) exhibit selectivity
      for the inhibition of neuronal nicotinic acetylcholine receptors (nAChRs). This
      study characterizes the mechanism of selective long-term inhibition of neuronal
      and muscle-neuronal chimeric nAChRs by bis(2,2,6,6-tetramethyl-4-piperidinyl)
      sebacate (bis-TMP-10 or BTMPS), a bifunctional form of the potent ganglionic
      blocker tetramethylpiperidine. Long-term inhibition of neuronal nAChRs by bis-TMP
      10 has been previously demonstrated to arise, at least in part, from the binding
      of the bis compound to neuronal beta-subunits. In this study, long-term
      inhibition is demonstrated to be dependent upon the presence of sequence
      element(s) within the pore-lining second transmembrane domain (tm2) of neuronal
      beta-subunits; however, the inhibitor binding site itself does not appear to be
      contained within the segment of the channel pore influenced by the membrane
      electric field. Specifically, our results imply that bis-TMP-10 interacts with an
      activation-sensitive element, the availability of which may be regulated by a
      sequence in the tm2 domain. Furthermore, we demonstrate a compound length
      requirement for long-term inhibition that would be consistent with binding to
      multiple sites located on the extracellular portion of the receptor.

PMID- 9591659
TI  - Interaction of permeant and blocking ions in cloned inward-rectifier K+ channels.
AB  - Blocking cloned inward-rectifier potassium (Kir) channels from the cytoplasmic
      side was analyzed with a rapid application system exchanging the intracellular
      solution on giant inside-out patches from Xenopus oocytes in <2 ms. Dependence of
      the pore-block on interaction of the blocking molecule with permeant and
      impermeant ions on either side of the membrane was investigated in Kir1.1 (ROMK1)
      channels blocked by ammonium derivatives and in Kir4.1 (BIR10) channels blocked
      by spermine. The blocking reaction in both systems showed first-order kinetics
      and allowed separate determination of on- and off-rates. The off-rates of block
      were strongly dependent on the concentration of internal and external bulk ions,
      but almost independent of the ion species at the cytoplasmic side of the
      membrane. With K+ as the only cation on both sides of the membrane, off-rates
      exhibited strong coupling to the K+ reversal potential (E(K)) and increased and
      decreased with reduction in intra and extracellular K+ concentration,
      respectively. The on-rates showed significant dependence on concentration and
      species of internal bulk ions. This control of rate-constants by interaction of
      permeant and impermeant internal and external ions governs the steady-state
      current-voltage relation (I-V) of Kir channels and determines their physiological
      function under various conditions.

PMID- 9591660
TI  - Anomalous mole fraction effect, electrostatics, and binding in ionic channels.
AB  - Ionic channels bathed in mixed solutions of two permeant electrolytes often
      conduct less current than channels bathed in pure solutions of either. For many
      years, this anomalous mole fraction effect (AMFE) has been thought to occur only
      in single-file pores containing two or more ions at a time. Most thinking about
      channels incorporates this view. We show here that the AMFE arises naturally, as
      an electrostatic consequence of localized ion specific binding, if the average
      current through a channel is described by a theory (Poisson-Nernst-Planck, PNP)
      that computes the average electric field from the average concentration of
      charges in and near the channel. The theory contains only those ion-ion
      interactions mediated by the mean field, and it does not enforce single filing.
      The AMFE is predicted by PNP over a wide range of mean concentrations of ions in
      the channel; for example, it is predicted when (on the average) less, or much
      less, than one ion is found in the channel's pore. In this treatment, the AMFE
      arises, in large measure, from a depletion layer produced near a region of ion
      specific binding. The small excess concentration of ions in the binding region
      repels all nearby ions of like charge, thereby creating a depletion layer. The
      overall conductance of the channel arises in effect from resistors in series, one
      from the binding region, one from the depletion zone, and one from the unbinding
      region. The highest value resistor (which occurs in the depletion zone) limits
      the overall series conductance. Here the AMFE is not the result of single filing
      or multiple occupancy, and so previous views of permeation need to be revised:
      the presence of an AMFE does not imply that ions permeate single file through a
      multiply occupied pore.

PMID- 9591661
TI  - ATP inhibition and rectification of a Ca2+-activated anion channel in
      sarcoplasmic reticulum of skeletal muscle.
AB  - We describe ATP-dependent inhibition of the 75-105-pS (in 250 mM Cl-) anion
      channel (SCl) from the sarcoplasmic reticulum (SR) of rabbit skeletal muscle. In
      addition to activation by Ca2+ and voltage, inhibition by ATP provides a further
      mechanism for regulating SCl channel activity in vivo. Inhibition by the
      nonhydrolyzable ATP analog 5'-adenylylimidodiphosphate (AMP-PNP) ruled out a
      phosphorylation mechanism. Cytoplasmic ATP (approximately 1 mM) inhibited only
      when Cl- flowed from cytoplasm to lumen, regardless of membrane voltage. Flux in
      the opposite direction was not inhibited by 9 mM ATP. Thus ATP causes true,
      current rectification in SCl channels. Inhibition by cytoplasmic ATP was also
      voltage dependent, having a K(I) of 0.4-1 mM at -40 mV (Hill coefficient
      approximately 2), which increased at more negative potentials. Luminal ATP
      inhibited with a K(I) of approximately 2 mM at +40 mV, and showed no block at
      negative voltages. Hidden Markov model analysis revealed that ATP inhibition 1)
      reduced mean open times without altering the maximum channel amplitude, 2) was
      mediated by a novel, single, voltage-independent closed state (approximately 1
      ms), and 3) was much less potent on lower conductance substates than the higher
      conductance states. Therefore, the SCl channel is unlikely to pass Cl- from
      cytoplasm to SR lumen in vivo, and balance electrogenic Ca2+ uptake as previously
      suggested. Possible roles for the SCl channel in the transport of other anions
      are discussed.

PMID- 9591662
TI  - Inactivation of Ca2+ release channels (ryanodine receptors RyR1 and RyR2) with
      rapid steps in [Ca2+] and voltage.
AB  - The transient responses of sheep cardiac and rabbit skeletal ryanodine receptors
      (RyRs) to step changes in membrane potential and cytosolic [Ca2+] were measured.
      Both cardiac and skeletal RyRs have two voltage-dependent inactivation processes
      (tau approximately 1-3 s at +40 mV) that operate at opposite voltage extremes.
      Approximately one-half to two-thirds of RyRs inactivated when the bilayer voltage
      was stepped either way between positive and negative values. Inactivation was not
      detected (within 30 s) in RyRs with Po less than 0.2. Inactivation rates
      increased with intraburst open probability (Po) and in proportion to the
      probability of a long-lived, RyR open state (P(OL)) RyR inactivation depended on
      P(OL) and not on the particular activator (Ca2+ (microM), ATP, caffeine, and
      ryanodine), inhibitor (mM Ca2+ and Mg2+), or gating mode. The activity of one
      half to two-thirds of RyRs declined (i.e., the RyRs inactivated) after [Ca2+]
      steps from subactivating (0.1 microM) to activating (1-100 microM) levels. This
      was due to the same inactivation mechanism responsible for inactivation after
      voltage steps. Both forms of inactivation had the same kinetics and similar
      dependencies on Po and voltage. Moreover, RyRs that failed to inactivate after
      voltage steps also did not inactivate after [Ca2+] steps. The inactivating
      response to [Ca2+] steps (0.1-1 microM) was not RyRs "adapting" to steady [Ca2+]
      after the step, because a subsequent step from 1 to 100 microM failed to
      reactivate RyRs.

PMID- 9591664
TI  - Fusion pore conductance: experimental approaches and theoretical algorithms.
AB  - Time-resolved admittance measurements provide the basis for studies showing that
      membrane fusion occurs through the formation and widening of an initially small
      pore, linking two previously separated aqueous compartments. Here we introduce
      modifications to this method that correct the cell-pipette (source) admittance
      for attenuation and phase shifts produced by electrophysiological equipment. Two
      new approaches for setting the right phase angle are discussed. The first uses
      the displacement of a patch-clamp amplifier C-slow potentiometer for the
      calculation of phase. This calculation is based on amplitudes of observed and
      expected (theoretical) changes in the source admittance. The second approach
      automates the original phase adjustment, the validity of which we prove
      analytically for certain conditions. The multiple sine wave approach is modified
      to allow the calculation of target cell membrane parameters and the conductance
      of the fusion pore. We also show how this technique can be extended for
      measurements of the resting potential of the first (voltage-clamped) membrane. We
      introduce an algorithm for calculation of fusion pore conductance despite a
      concurrent change in the resistance of the clamped membrane. The sensitivity of
      the capacitance restoration algorithm to phase shift errors is analyzed, and
      experimental data are used to demonstrate the results of this analysis. Finally,
      we show how the phase offset can be corrected "off-line" by restoring the shape
      of the capacitance increment.

PMID- 9591665
TI  - Surface dipole potential at the interface between water and self-assembled
      monolayers of phosphatidylserine and phosphatidic acid.
AB  - The nature and magnitude of the surface dipole potential chi at a membrane/water
      interface still remain open to discussion. By combining measurements of
      differential capacity C and charge density sigma at the interface between self
      assembled monolayers of phosphatidylserine and phosphatidic acid supported by
      mercury and aqueous electrolytes of different concentration and pH, a sigmoidal
      dependence of chi upon sigma is revealed, with the inflection at sigma = 0. This
      behavior is strongly reminiscent of the surface dipole potential due to
      reorientation of adsorbed water molecules at electrified interfaces. The small
      increase in C with a decrease in the frequency of the AC signal below
      approximately 80 Hz, as observed with phospholipid monolayers with partially
      protonated polar groups, is explained either by a sluggish collective
      reorientation of some polar groups of the lipid or by a sluggish movement of
      protons across the polar head region.

PMID- 9591663
TI  - ATP transport through a single mitochondrial channel, VDAC, studied by current
      fluctuation analysis.
AB  - The "molecular Coulter counter" concept has been used to study transport of ATP
      molecules through the nanometer-scale aqueous pore of the voltage-dependent
      mitochondrial ion channel, VDAC. We examine the ATP-induced current fluctuations
      and the change in average current through a single fully open channel
      reconstituted into a planar lipid bilayer. At high salt concentration (1 M NaCl),
      the addition of ATP reduces both solution conductivity and channel conductance,
      but the effect on the channel is several times stronger and shows saturation
      behavior even at 50 mM ATP concentration. These results and simple steric
      considerations indicate pronounced attraction of ATP molecules to VDAC's aqueous
      pore and permit us to evaluate the effect of a single ATP molecule on channel
      conductance. ATP addition also generates an excess noise in the ionic current
      through the channel. Analysis of this excess noise shows that its spectrum is
      flat in the accessible frequency interval up to several kilohertz. ATP exchange
      between the pore and the bulk is fast enough not to display any dispersion at
      these frequencies. By relating the low-frequency spectral density of the noise to
      the equilibrium diffusion of ATP molecules in the aqueous pore, we calculate a
      diffusion coefficient D = (1.6-3.3)10(-11) m2/s. This is one order of magnitude
      smaller than the ATP diffusion coefficient in the bulk, but it agrees with recent
      results on ATP flux measurements in multichannel membranes using the
      luciferin/luciferase method.

PMID- 9591666
TI  - Atomic force microscope imaging of phospholipid bilayer degradation by
      phospholipase A2.
AB  - We have investigated the time course of the degradation of a supported
      dipalmitoylphosphatidylcholine bilayer by phospholipase A2 in aqueous buffer with
      an atomic force microscope. Contact mode imaging allows visualization of enzyme
      activity on the substrate with a lateral resolution of less than 10 nm. Detailed
      analysis of the micrographs reveals a dependence of enzyme activity on the
      phospholipid organization and orientation in the bilayer. These experiments
      suggest that it is possible to observe single enzymes at work in small channels,
      which are created by the hydrolysis of membrane phospholipids. Indeed, the
      measured rate of hydrolysis of phospholipids corresponds very well with the
      enzyme activity found in kinetic studies. It was also possible to correlate the
      number of enzymes at the surface, as calculated from the binding constant to the
      number of starting points of the hydrolysis. In addition, the width of the
      channels was found to be comparable to the diameter of a single phospholipase A2
      and thus further supports the single-enzyme hypothesis.

PMID- 9591667
TI  - Magnetically aligned phospholipid bilayers with positive ordering: a new model
      membrane system.
AB  - A stable smectic phospholipid bilayer phase aligned with the director parallel to
      the magnetic field can be generated by the addition of certain trivalent
      paramagnetic lanthanide ions to a bicellar solution of
      dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC) in
      water. Suitable lanthanide ions are those with positive anisotropy of their
      magnetic susceptibility, namely Eu3+, Er3+, Tm3+, and Yb3+. For samples doped
      with Tm3+, this phase extends over a wide range of Tm3+ concentrations (6-40 mM)
      and temperatures (35-90 degrees C) and appears to undergo a transition from a
      fluid nematic discotic to a fluid, but highly ordered, smectic phase at a
      temperature that depends on the thulium concentration. As a membrane mimetic,
      these new, positively ordered phospholipid phases have high potential for
      structural studies using a variety of techniques such as magnetic resonance (EMR
      and NMR), small-angle x-ray and neutron diffraction, as well as optical and
      infrared spectroscopy.

PMID- 9591668
TI  - Determination of the hydrocarbon core structure of fluid dioleoylphosphocholine
      (DOPC) bilayers by x-ray diffraction using specific bromination of the double
      bonds: effect of hydration.
AB  - Changes in the structure of the hydrocarbon core (HC) of fluid lipid bilayers can
      reveal how bilayers respond to the partitioning of peptides and other solutes
      (Jacobs, R. E., and S. H. White. 1989. Biochemistry. 28:3421-3437). The structure
      of the HC of dioleoylphosphocholine (DOPC) bilayers can be determined from the
      transbilayer distribution of the double-bonds (Wiener, M. C., and S. H. White.
      1992. Biophys. J. 61:434-447). This distribution, representing the time-averaged
      projection of the double-bond positions onto the bilayer normal (z), can be
      obtained by means of neutron diffraction and double-bond specific deuteration
      (Wiener, M. C., G. I. King, and S. H. White. 1991. Biophys. J. 60:568-576). For
      fully resolved bilayer profiles, a close approximation of the distribution could
      be obtained by x-ray diffraction and isomorphous bromine labeling at the double
      bonds of the DOPC sn-2 acyl chain (Wiener, M. C., and S. H. White. 1991.
      Biochemistry. 30:6997-7008). We have modified the bromine-labeling approach in a
      manner that permits determination of the distribution in under-resolved bilayer
      profiles observed at high water contents. We used this new method to determine
      the transbilayer distribution of the double-bond bromine labels of DOPC over a
      hydration range of 5.4 to 16 waters per lipid, which reveals how the HC structure
      changes with hydration. We found that the transbilayer distributions of the
      bromines can be described by a pair of Gaussians of 1/e half-width A(Br) located
      at z = +Z(Br) relative to the bilayer center. For hydrations from 5.4 waters up
      to 9.4 waters per lipid, Z(Br) decreases from 7.97 +/- 0.27 A to 6.59 +/- 0.15 A,
      while A(Br) increased from 4.62 +/- 0.62 A to 5.92 +/- 0.37 A, consistent with
      the expected hydration-induced decrease in HC thickness and increase in area per
      lipid. After the phosphocholine hydration shell was filled at approximately 12
      waters per lipid, we observed a shift in Z(Br) to approximately 7.3 A, indicative
      of a distinct structural change upon completion of the hydration shell. For
      hydrations of 12-16 waters per lipid, the bromine distribution remains constant
      at Z(Br) = 7.33 +/- 0.25 A and A(Br) = 5.35 +/- 0.5 A. The absolute-scale
      structure factors obtained in the experiments provided an opportunity to test the
      so-called fluid-minus method of structure-factor scaling. We found that the
      method is quite satisfactory for determining the phases of structure factors, but
      not their absolute values.

PMID- 9591669
TI  - Intramembrane molecular dipoles affect the membrane insertion and folding of a
      model amphiphilic peptide.
AB  - The relationship between the dipole potential and the interaction of the
      mitochondrial amphipathic signal sequence known as p25 with model membranes has
      been studied using 1-(3-sulfonatopropyl)-4-[beta[2-(di-n-octyl-amino)-6
      naphthyl]viny l] pyridinium betaine (di-8-ANEPPS) as a fluorescent probe. The
      dipole potential of phosphatidylcholine membranes was modified by incorporating
      into the bilayer the sterols phloretin and 6-ketocholestanol (KC), which decrease
      and increase the dipole potential, respectively. The results derived from the
      application of a dual-wavelength ratiometric fluorescence method for following
      the variation of the membrane dipole potential have shown that when p25 inserts
      into the lipidic bilayer, a decrease in the dipole potential takes place. The
      magnitude of this decrease depends on the initial value of the dipole potential,
      i.e., before interaction with the peptide. Thus, when KC was incorporated into
      the bilayer, the decrease caused by the membrane insertion of p25 was larger than
      that caused in PC membranes. Alternatively, in the presence of phloretin, the
      decrease in the potential caused by the peptide insertion was smaller.
      Complementary studies involving attenuated total reflectance-Fourier transform
      infrared spectroscopy of the peptide membrane interactions have shown that
      modification of the dipole potential affects the conformation of the peptide
      during the course of its interaction with the membrane. The presence of KC
      induces a higher amount of helicoidal structure. The presence of phloretin,
      however, does not appear to affect the secondary structure of the peptide. The
      differences observed in the dipole potential decreases caused by the presence of
      the peptide with the PC membranes and phloretin-PC membranes, therefore, must
      involve differences in the tertiary and, perhaps, quaternary conformations of
      p25.

PMID- 9591670
TI  - Direct detection of domains in phospholipid bilayers by grazing incidence
      diffraction of neutrons and atomic force microscopy.
AB  - The geometry of domains in phospholipid bilayers of binary (1:1) mixtures of
      synthetic lecithins with a difference in chain length of four methylene groups
      has been studied by two independent, direct and complementary methods. Grazing
      incidence diffraction of neutrons provided gel domain sizes of less than 10 nm in
      both the gel and the coexistence phase of the mixture, while no domains were
      detected for the fluid phase. For the coexistence region, the neutron data
      suggest that domains grow in number rather than in size with decreasing
      temperature. Atomic force microscopy was used to study gel phase size and shape
      of the domains. The domains imaged by atomic force microscopy exhibit a rather
      irregular shape with an average size of 10 nm, thus confirming the neutron
      results for this phase. The good agreement between atomic force microscopy and
      neutron results, despite the completely different nature of their observables,
      has potential for the future development of refined models for the interpretation
      of neutron data from heterogeneous membranes in terms of regularly spaced and
      spatially extended scatterers.

PMID- 9591671
TI  - Luminescence resonance energy transfer measurements in myosin.
AB  - Myosin is thought to generate force by a rotation between the relative
      orientations of two domains. Direct measurements of distances between the domains
      could potentially confirm and quantify these conformational changes, but efforts
      have been hampered by the large distances involved. Here we show that
      luminescence resonance energy transfer (LRET), which uses a luminescent
      lanthanide as the energy-transfer donor, is capable of measuring these long
      distances. Specifically, we measure distances between the catalytic domain
      (Cys707) and regulatory light chain domain (Cys108) of the myosin head. An energy
      transfer efficiency of 21.2 +/- 1.9% is measured in the myosin complex without
      nucleotide or actin, corresponding to a distance of 73 A, consistent with the
      crystal structure of Rayment et al. Upon binding to actin, the energy transfer
      efficiency decreases by 4.5 +/- 1.0%, indicating a conformational change in
      myosin that involves a relative rotation and/or translation of Cys707 relative to
      the light chain domain. Addition of ADP also alters the energy transfer
      efficiency, likely through a rotation of the probe attached to Cys707. These
      results demonstrate that LRET is capable of making accurate measurements on the
      relatively large actomyosin complex, and is capable of detecting conformational
      changes between the catalytic and light chain domains of myosin.

PMID- 9591673
TI  - Effect of Ca2+-Mg2+ exchange on the flexibility and/or conformation of the small
      domain in monomeric actin.
AB  - A fluorescence resonance energy transfer (FRET) parameter, f' (defined as the
      average transfer efficiency, (E), normalized by the actual fluorescence intensity
      of the donor in the presence of acceptor, F(DA)), was previously shown to be
      capable of monitoring both changes in local flexibility of the protein matrix and
      major conformational transitions. The temperature profile of this parameter was
      used to detect the change of the protein flexibility in the small domain of the
      actin monomer (G-actin) upon the replacement of Ca2+ by Mg2+. The Cys-374 residue
      of the actin monomer was labeled with N-iodoacetyl-N'-(5-sulfo-1
      naphthyl)ethylenediamine (IAEDANS) to introduce a fluorescence donor and the Lys
      61 residue with fluorescein-5-isothiocyanate (FITC) to serve as an acceptor. The
      f' increases with increasing temperature over the whole temperature range for Mg
      G-actin. This parameter increases similarly in the case of Ca-G-actin up to 26
      degrees C, whereas an opposite tendency appears above this temperature. These
      data indicate that there is a conformational change in Ca-G-actin above 26
      degrees C that was not detected in the case of Mg-G-actin. In the temperature
      range between 6 degrees C and 26 degrees C the slope of the temperature profile
      of f' is the same for Ca-G-actin and Mg-G-actin, suggesting that the flexibility
      of the protein matrix between the two labels is identical in the two forms of
      actin.

PMID- 9591672
TI  - The stiffness of skeletal muscle in isometric contraction and rigor: the fraction
      of myosin heads bound to actin.
AB  - Step changes in length (between -3 and +5 nm per half-sarcomere) were imposed on
      isolated muscle fibers at the plateau of an isometric tetanus (tension T0) and on
      the same fibers in rigor after permeabilization of the sarcolemma, to determine
      stiffness of the half-sarcomere in the two conditions. To identify the
      contribution of actin filaments to the total half-sarcomere compliance (C),
      measurements were made at sarcomere lengths between 2.00 and 2.15 microm, where
      the number of myosin cross-bridges in the region of overlap between the myosin
      filament and the actin filament remains constant, and only the length of the
      nonoverlapped region of the actin filament changes with sarcomere length. At 2.1
      microm sarcomere length, C was 3.9 nm T0(-1) in active isometric contraction and
      2.6 nm T0(-1) in rigor. The actin filament compliance, estimated from the slope
      of the relation between C and sarcomere length, was 2.3 nm microm(-1) T0(-1).
      Recent x-ray diffraction experiments suggest that the myosin filament compliance
      is 1.3 nm microm(-1) T0(-1). With these values for filament compliance, the
      difference in half-sarcomere compliance between isometric contraction and rigor
      indicates that the fraction of myosin cross-bridges attached to actin in
      isometric contraction is not larger than 0.43, assuming that cross-bridge
      elasticity is the same in isometric contraction and rigor.

PMID- 9591674
TI  - Structural variability and new intermolecular interactions of Z-DNA in crystals
      of d(pCpGpCpGpCpG).
AB  - We have determined the single crystal x-ray structure of the synthetic DNA
      hexamer d(pCpGpCpGpCpG) in two different crystal forms. The hexamer pCGCGCG has
      the Z-DNA conformation and in both cases the asymmetric unit contains more than
      one Z-DNA duplex. Crystals belong to the space group C222(1) with a = 69.73, b =
      52.63, and c = 26.21 A, and to the space group P2(1) with a = 49.87, b = 41.26, c
      = 21.91 A, and gamma = 97.12 degrees. Both crystals show new crystal packing
      modes. The molecules also show striking new features when compared with
      previously determined Z-DNA structures: 1) the bases in one duplex have a large
      inclination with respect to the helical axis, which alters the overall shape of
      the molecule. 2) Some cytosine nitrogens interact by hydrogen bonding with
      phosphates in neighbor molecules. Similar base-phosphate interactions had been
      previously detected in some B-DNA crystals. 3) Basepair stacking between the ends
      of neighbor molecules is variable and no helical continuity is maintained between
      contiguous hexamer duplexes.

PMID- 9591675
TI  - Modeling chain folding in protein-constrained circular DNA.
AB  - An efficient method for sampling equilibrium configurations of DNA chains binding
      one or more DNA-bending proteins is presented. The technique is applied to obtain
      the tertiary structures of minimal bending energy for a selection of
      dinucleosomal minichromosomes that differ in degree of protein-DNA interaction,
      protein spacing along the DNA chain contour, and ring size. The protein-bound
      portions of the DNA chains are represented by tight, left-handed supercoils of
      fixed geometry. The protein-free regions are modeled individually as elastic
      rods. For each random spatial arrangement of the two nucleosomes assumed during a
      stochastic search for the global minimum, the paths of the flexible connecting
      DNA segments are determined through a numerical solution of the equations of
      equilibrium for torsionally relaxed elastic rods. The minimal energy forms reveal
      how protein binding and spacing and plasmid size differentially affect folding
      and offer new insights into experimental minichromosome systems.

PMID- 9591676
TI  - New measurements of DNA twist elasticity.
AB  - The symmetries of the DNA double helix require a new term in its linear response
      to stress: the coupling between twist and stretch. Recent experiments with
      torsionally constrained single molecules give the first direct measurement of
      this new material parameter. We extract its value from a recent experiment.
      Finally, we sketch the effect of constrained twist on entropic elasticity of DNA
      arising from the connection between Link, Twist, and Writhe.

PMID- 9591677
TI  - Remarks on discrete and continuous large-scale models of DNA dynamics.
AB  - We present a comparison of the continuous versus discrete models of large-scale
      DNA conformation, focusing on issues of relevance to molecular dynamics. Starting
      from conventional expressions for elastic potential energy, we derive elastic
      dynamic equations in terms of Cartesian coordinates of the helical axis curve,
      together with a twist function representing the helical or excess twist. It is
      noted that the conventional potential energies for the two models are not
      consistent. In addition, we derive expressions for random Brownian forcing for
      the nonlinear elastic dynamics and discuss the nature of such forces in a
      continuous system.

PMID- 9591678
TI  - The elastic rod model for DNA and its application to the tertiary structure of
      DNA minicircles in mononucleosomes.
AB  - Explicit solutions to the equations of equilibrium in the theory of the elastic
      rod model for DNA are employed to develop a procedure for finding the
      configuration that minimizes the elastic energy of a minicircle in a
      mononucleosome with specified values of the minicircle size N in base pairs, the
      extent w of wrapping of DNA about the histone core particle, the helical repeat
      h(0)b of the bound DNA, and the linking number Lk of the minicircle. The
      procedure permits a determination of the set Y(N, w, h(0)b) of integral values of
      Lk for which the minimum energy configuration does not involve self-contact, and
      graphs of writhe versus w are presented for such values of Lk. For the range of N
      of interest here, 330 < N < 370, the set Y(N, w, h(0)b) is of primary importance:
      when Lk is not in Y(N, w, h(0)b), the configurations compatible with Lk have
      elastic energies high enough to preclude the occurrence of an observable
      concentration of topoisomer Lk in an equilibrium distribution of topoisomers.
      Equilibrium distributions of Lk, calculated by setting differences in the free
      energy of the extranucleosomal loop equal to differences in equilibrium elastic
      energy, are found to be very close to Gaussian when computed under the assumption
      that w is fixed, but far from Gaussian when it is assumed that w fluctuates
      between two values. The theoretical results given suggest a method by which one
      may calculate DNA-histone binding energies from measured equilibrium
      distributions of Lk.

PMID- 9591680
TI  - A theory of thermal fluctuations in DNA miniplasmids.
AB  - A recent analysis of the normal modes of vibration of a ring formed by bringing
      together and sealing, with or without the addition of twist, the ends of rods
      that are straight when stress free is taken as the basis for a theory of the
      statistical thermodynamics of a canonical ensemble of DNA minicircles with
      specified linking number difference deltaLk and number N of base pairs. It is
      assumed that N corresponds to a circumference in the range of one or two
      persistence lengths. For such an ensemble, the theory yields an expression for
      the average writhe (Wr), which can be employed to calculate the free energy,
      entropy, and enthalpy of supercoiling, deltaGsc, deltaSsc, and deltaHsc. The
      results obtained for the dependence of deltaGsc on deltaLk and N are in accord
      with experimental observations of equilibrium distributions of topoisomers of
      plasmids with N approximately 200 bp.

PMID- 9591679
TI  - A topological approach to nucleosome structure and dynamics: the linking number
      paradox and other issues.
AB  - The linking number paradox of DNA in chromatin (two negative crossings around the
      octamer, associated with a unit linking number reduction), which is 21 years old
      this year, has come of age. After stirring much debate in the past, the initially
      hypothetical explanation of the paradox by DNA overtwisting on the nucleosome
      surface is now presented as a hard fact in recent textbooks. The first part of
      this article presents a historical perspective of the problem and details the
      numerous attempts to measure DNA local periodicity, which in one remarkable
      example sowed the seeds for the discovery of DNA bending. The second part is
      devoted to the DNA minicircle system, which has been developed in the author's
      laboratory as an alternative to the local-periodicity-measurement approach. It
      offers a simple proposal: a unit linking number reduction associated with a
      single crossing. This conclusion is contrasted with the latest high-resolution
      crystallographic data of the nucleosome in the third part of the article, and the
      fourth part examines the available evidence supporting an extension of these
      results to nucleosomes in chromatin. The last part addresses another basic
      question pertaining to nucleosome dynamics, the conformational flexibility of the
      histone tetramer.

PMID- 9591681
TI  - Chromatin fiber structure: morphology, molecular determinants, structural
      transitions.
AB  - Despite more than 20 years of research, the structure of the chromatin fiber and
      its molecular determinants remain enigmatic. Recent developments in high
      resolution microscopic techniques, as well as the application of mathematical
      modeling to chromatin fiber structure, have allowed the acquisition of some new
      insights into the structure and its determinants. Here we present some of the
      newest data on the structure of the chromatin fiber in both its extended and
      compacted states, and bring together this new knowledge with older data in an
      attempt to provide a unified view of how chromatin components interact with each
      other to form its various conformations. The structural transitions that are
      believed to take place during transcriptional activation and its cessation are
      also discussed. It becomes obvious that despite some progress in our
      understanding of the fiber structure and its dynamics, huge gaps continue to
      exist. Bridging these gaps will require further improvements in already available
      techniques and the introduction of completely new approaches.

PMID- 9591683
TI  - The protein environment surrounding tyrosyl radicals D. and Z. in photosystem II:
      a difference Fourier-transform infrared spectroscopic study.
AB  - Photosystem II contains two redox-active tyrosine residues, termed D and Z, which
      have different midpoint potentials and oxidation/reduction kinetics. To
      understand the functional properties of redox-active tyrosines, we report a
      difference Fourier-transform infrared (FT-IR) spectroscopic study of these
      species. Vibrational spectra associated with the oxidation of each tyrosine
      residue are acquired; electron paramagnetic resonance (EPR) and fluorescence
      experiments demonstrate that there is no detectable contribution of Q(A)- to
      these spectra. Vibrational lines are assigned to the radicals by isotopic
      labeling of tyrosine. Global 15N labeling, 2H exchange, and changes in pH
      identify differences in the reversible interactions of the two redox-active
      tyrosines with N-containing, titratable amino acid side chains in their
      environments. To identify the amino acid residue that contributes to the spectrum
      of D, mutations at His189 in the D2 polypeptide were examined. Mutations at this
      site result in substantial changes in the spectrum of tyrosine D. Previously,
      mutations at the analogous histidine, His190 in the D1 polypeptide, were shown to
      have no significant effect on the FT-IR spectrum of tyrosine Z (Bernard, M. T.,
      et al. 1995. J. Biol. Chem. 270:1589-1594). A disparity in the number of
      accessible, proton-accepting groups could influence electron transfer rates and
      energetics and account for functional differences between the two redox-active
      tyrosines.

PMID- 9591682
TI  - Electron transfer and protein dynamics in the photosynthetic reaction center.
AB  - We have measured the kinetics of electron transfer (ET) from the primary quinone
      (Q(A)) to the special pair (P) of the reaction center (RC) complex from
      Rhodobacter sphaeroides as a function of temperature (5-300 K), illumination
      protocol (cooled in the dark and under illumination from 110, 160, 180, and 280
      K), and warming rate (1.3 and 13 mK/s). The nonexponential kinetics are
      interpreted with a quantum-mechanical ET model (Fermi's golden rule and the spin
      boson model), in which heterogeneity of the protein ensemble, relaxations, and
      fluctuations are cast into a single coordinate that relaxes monotonically and is
      sensitive to all types of relaxations caused by ET. Our analysis shows that the
      structural changes that occur in response to ET decrease the free energy gap
      between donor and acceptor states by 120 meV and decrease the electronic coupling
      between donor and acceptor states from 2.7 x 10(-4) cm(-1) to 1.8 x 10(-4) cm(
      1). At cryogenic temperatures, conformational changes can be slowed or completely
      arrested, allowing us to monitor relaxations on the annealing time scale
      (approximately 10(3)-10(4) s) as well as the time scale of ET (approximately 100
      ms). The relaxations occur within four broad tiers of conformational substates
      with average apparent Arrhenius activation enthalpies of 17, 50, 78, and 110
      kJ/mol and preexponential factors of 10(13), 10(15), 10(21), and 10(25) s(-1),
      respectively. The parameterization provides a prediction of the time course of
      relaxations at all temperatures. At 300 K, relaxations are expected to occur from
      1 ps to 1 ms, whereas at lower temperatures, even broader distributions of
      relaxation times are expected. The weak dependence of the ET rate on both
      temperature and protein conformation, together with the possibility of modeling
      heterogeneity and dynamics with a single conformational coordinate, make RC a
      useful model system for probing the dynamics of conformational changes in
      proteins.

PMID- 9591684
TI  - Photochromic polypeptides as synthetic models of biological photoreceptors: a
      spectroscopic study.
AB  - L-Glutamic acid polypeptides containing photochromic nitrospiropyran bound to the
      side chains at various percentages ("local" concentration) have been synthesized
      and investigated as possible artificial models of biological photoreceptors.
      Absorption and fluorescence spectroscopy have been utilized to investigate the
      photophysical and photochemical properties of nitrospiropyrans, both inserted in
      the polypeptide chain and in solution as "free" dye. Conformational variations
      produced by dark storage and light exposure of the photochromic polypeptides have
      been studied by means of circular dichroism. Dark-kept "free" dyes in hexafluoro
      2-propanol solution in the merocyanine form ("open" form) give rise to molecular
      aggregates, which have been characterized as merocyanine dimers. The equilibrium
      constant between the monomer and the dimer, K, and their molar extinction
      coefficients, epsilon, at several wavelengths have been determined. Fluorescence
      measurements on "free" and polypeptide-bound nitrospiropyrans suggest that the
      dimerization process between merocyanines is favored when the photochromic units
      are inserted in the polypeptide chain and that under these conditions an
      efficient energy transfer from the monomer (donor) to the dimer (acceptor)
      occurs. By varying "local" as well as total nitrospiropyran concentration, it has
      been shown that the dimeric species result from intermolecular interactions
      between photochromic groups inserted in the same polypeptide chain. The alpha
      helix --> random coil transition of the polypeptide structure after dark storage
      has eventually been shown to be the result of the dimerization process and not of
      the dark isomerization per se from the "closed" spiropyran form to the "open"
      merocyanine form of the dye.

PMID- 9591685
TI  - Energy transfer and charge separation in photosystem I: P700 oxidation upon
      selective excitation of the long-wavelength antenna chlorophylls of Synechococcus
      elongatus.
AB  - Photosystem I of the cyanobacterium Synechococcus elongatus contains two spectral
      pools of chlorophylls called C-708 and C-719 that absorb at longer wavelengths
      than the primary electron donor P700. We investigated the relative quantum yields
      of photochemical charge separation and fluorescence as a function of excitation
      wavelength and temperature in trimeric and monomeric photosystem I complexes of
      this cyanobacterium. The monomeric complexes are characterized by a reduced
      content of the C-719 spectral form. At room temperature, an analysis of the
      wavelength dependence of P700 oxidation indicated that all absorbed light, even
      of wavelengths of up to 750 nm, has the same probability of resulting in a stable
      P700 photooxidation. Upon cooling from 295 K to 5 K, the nonselectively excited
      steady-state emission increased by 11- and 16-fold in the trimeric and monomeric
      complexes, respectively, whereas the quantum yield of P700 oxidation decreased
      2.2- and 1.7-fold. Fluorescence excitation spectra at 5 K indicate that the
      fluorescence quantum yield further increases upon scanning of the excitation
      wavelength from 690 nm to 710 nm, whereas the quantum yield of P700 oxidation
      decreases significantly upon excitation at wavelengths longer than 700 nm. Based
      on these findings, we conclude that at 5 K the excited state is not equilibrated
      over the antenna before charge separation occurs, and that approximately 50% of
      the excitations reach P700 before they become irreversibly trapped on one of the
      long-wavelength antenna pigments. Possible spatial organizations of the long
      wavelength antenna pigments in the three-dimensional structure of photosystem I
      are discussed.

PMID- 9591686
TI  - Protein modifications affecting triplet energy transfer in bacterial
      photosynthetic reaction centers.
AB  - The efficiency of triplet energy transfer from the special pair (P) to the
      carotenoid (C) in photosynthetic reaction centers (RCs) from a large family of
      mutant strains has been investigated. The mutants carry substitutions at
      positions L181 and/or M208 near chlorophyll-based cofactors on the inactive and
      active sides of the complex, respectively. Light-modulated electron paramagnetic
      resonance at 10 K, where triplet energy transfer is thermally prohibited, reveals
      that the mutations do not perturb the electronic distribution of P. At
      temperatures > or = 70 K, we observe reduced signals from the carotenoid in most
      of the RCs with L181 substitutions. In particular, triplet transfer efficiency is
      reduced in all RCs in which a lysine at L181 donates a sixth ligand to the
      monomeric bacteriochlorophyll B(B). Replacement of the native Tyr at M208 on the
      active side of the complex with several polar residues increased transfer
      efficiency. The difference in the efficiencies of transfer in the RCs
      demonstrates the ability of the protein environment to influence the electronic
      overlap of the chromophores and thus the thermal barrier for triplet energy
      transfer.

PMID- 9591688
TI  - Characterization of the growth of 2D protein crystals on a lipid monolayer by
      ellipsometry and rigidity measurements coupled to electron microscopy.
AB  - We present here some sensitive optical and mechanical experiments for monitoring
      the process of formation and growth of two-dimensional (2D) crystals of proteins
      on a lipid monolayer at an air-water interface. The adsorption of proteins on the
      lipid monolayer was monitored by ellipsometry measurements. An instrument was
      developed to measure the shear elastic constant (in plane rigidity) of the
      monolayer. These experiments have been done using cholera toxin B subunit (CTB)
      and annexin V as model proteins interacting with a monosialoganglioside (GM1) and
      dioleoylphosphatidylserine (DOPS), respectively. Electron microscopy observations
      of the protein-lipid layer transferred to grids were systematically used as a
      control. We found a good correlation between the measured in-plane rigidity of
      the monolayer and the presence of large crystalline domains observed by electron
      microscopy grids. Our interpretation of these data is that the crystallization
      process of proteins on a lipid monolayer passes through at least three successive
      stages: 1) molecular recognition between protein and lipid-ligand, i.e.,
      adsorption of the protein on the lipid layer; 2) nucleation and growth of
      crystalline patches whose percolation is detected by the appearance of a non-zero
      in-plane rigidity; and 3) annealing of the layer producing a slower increase of
      the lateral or in-plane rigidity.

PMID- 9591687
TI  - Entropy-driven intermediate steps of oxygenation may regulate the allosteric
      behavior of hemoglobin.
AB  - When the oxygen binding isotherms of human, bovine and fallow deer (Dama-Dama)
      hemoglobins are measured at different temperatures either by optical or
      calorimetric techniques, analyses according to the Adair's formalism show that at
      least one of the intermediate steps of ligation has a positive enthalpy change,
      i.e., absorbs rather than emitting heat, indicating that it is entropy rather
      than enthalpy driven (Bucci, E., et al. 1991. Biochemistry. 30:3195-3199; Bucci,
      E., et al. 1993. Biochemistry. 32:3519-3526; Johnson, C., et al. 1992.
      Biochemistry. 31:10074-10082; Johnson, C., et al. 1995. Biophys. Chem. 59:107
      117). This phenomenon is confirmed in systems in which the beta82 lysines of
      human hemoglobin are covalently cross-linked by acylation with dicarboxylic acids
      of increasing length, namely the fumaryl (four-carbon-long), adipoyl (six-carbon
      long), and sebacoyl (10-carbon-long) residues. Consistently in all of the systems
      here reported, the enthalpy excursions are masked by compensatory entropy
      changes, which keep the free energy of ligand binding constant for the first
      three steps of oxygenation. Furthermore, the cooperativity index and the overall
      oxygen affinity seem to be correlated to the positive enthalpy excursions of the
      intermediate steps of ligation. Fumaryl-Hb (hemoglobin cross-linked with a
      fumaryl residue, four carbons) with the lowest absorption of heat has the highest
      affinity and lowest cooperativity index. Adipoyl-Hb (hemoglobin cross-linked with
      an adipoyl residue, six carbons) has the highest absorption of heat and the
      highest cooperativity index. It appears that nonuniform heat release by the
      intermediates of oxygenation is part of the allosteric phenomena in hemoglobin
      systems. There is not enough information that would allow assigning these
      phenomena to the interplay of the various conformations described for hemoglobin
      besides the classic T (Fermi et al. 1984. J. Mol. Biol. 175:159-174) and R
      (Shanaan. 1983. J. Mol. Biol. 171:31-59), as listed at the end of the Discussion.
      The possibility cannot be excluded that entropy-driven steps characterize new
      conformational transitions still to be described.

PMID- 9591689
TI  - Time-dependent effects of trimethylamine-N-oxide/urea on lactate dehydrogenase
      activity: an unexplored dimension of the adaptation paradigm.
AB  - Given that enzymes in urea-rich cells are believed to be just as sensitive to
      urea effects as enzymes in non-urea-rich cells, it is argued that time-dependent
      inactivation of enzymes by urea could become a factor of overriding importance in
      the biology of urea-rich cells. Time-independent parameters (e.g. Tm, k(cat), and
      Km) involving protein stability and enzyme function have generally been the focus
      of inquiries into the efficacy of naturally occurring osmolytes like
      trimethylamine-N-oxide (TMAO), to offset the deleterious effects of urea on the
      intracellular proteins in the urea-rich cells of elasmobranchs. However, using
      urea concentrations found in urea-rich cells of elasmobranches, we have found
      time-dependent effects on lactate dehydrogenase activity which indicate that TMAO
      plays the important biological role of slowing urea-induced dissociation of
      multimeric intracellular proteins. TMAO greatly diminishes the rate of lactate
      dehydrogenase dissociation and affords significant protection of the enzyme
      against urea-induced time-dependent inactivation. The effects of TMAO on enzyme
      inactivation by urea adds a temporal dimension that is an important part of the
      biology of the adaptation paradigm.

PMID- 9591690
TI  - Trimethylamine-N-oxide counteracts urea effects on rabbit muscle lactate
      dehydrogenase function: a test of the counteraction hypothesis.
AB  - Trimethylamine-N-oxide (TMAO) in the cells of sharks and rays is believed to
      counteract the deleterious effects of the high intracellular concentrations of
      urea in these animals. It has been hypothesized that TMAO has the generic ability
      to counteract the effects of urea on protein structure and function, regardless
      of whether that protein actually evolved in the presence of these two solutes.
      Rabbit muscle lactate dehydrogenase (LDH) did not evolve in the presence of
      either solute, and it is used here to test the validity of the counteraction
      hypothesis. With pyruvate as substrate, results show that its Km and the combined
      Km of pyruvate and NADH are increased by urea, decreased by TMAO, and in 1:1 and
      2:1 mixtures of urea:TMAO the Km values are essentially equivalent to the Km
      values obtained in the absence of the two solutes. In contrast, values of k(cat)
      and the Km for NADH as a substrate are unperturbed by urea, TMAO, or urea:TMAO
      mixtures. All of these effects are consistent with TMAO counteraction of the
      effects of urea on LDH kinetic parameters, supporting the premise that
      counteraction is a property of the solvent system and is independent of the
      evolutionary history of the protein.

PMID- 9591691
TI  - Electron crystallographic analysis of two-dimensional streptavidin crystals
      coordinated to metal-chelated lipid monolayers.
AB  - Coordination of individual histidine residues located on a protein surface to
      metal-chelated lipid monolayers is a potentially general method for crystallizing
      proteins in two dimensions. It was shown recently by Brewster angle microscopy
      (BAM) that the model protein streptavidin binds via its surface histidines to Cu
      DOIDA lipid monolayers, and aggregates into regularly shaped domains that have
      the appearance of crystals. We have used electron microscopy to confirm that the
      domains are indeed crystalline with lattice parameters similar to those of the
      same protein crystallized beneath biotinylated lipid monolayers. Although BAM
      demonstrates that the two-dimensional protein crystals grown via metal chelation
      are distinct from the biotin-bound crystals in both microscopic shape and
      thermodynamic behavior, the two crystal types show similar density projections
      and the same plane group symmetry.

PMID- 9591692
TI  - Aluminum phthalocyanine tetrasulfonate in MCF-10F, human breast epithelial cells:
      a hole burning study.
AB  - Laser-induced holes are burned in the absorption spectrum of aluminum
      phthalocyanine tetrasulfonate (APT) in MCF-10F, human breast epithelial cells.
      The hole burning mechanism is shown to be nonphotochemical. The fluorescence
      excitation spectra and hole spectra are compared with those of APT in
      hyperquenched glassy films of water, ethanol, and methanol. The results show that
      the APT is in an acidic, aqueous environment with a hydrogen-bonded network
      similar to that of glassy water, but showing the influence of other cellular
      components. Pressure shifts of holes allow the local compressibility about the
      APT to be determined.

PMID- 9591693
TI  - Separation of polystyrene microbeads using dielectrophoretic/gravitational field
      flow-fractionation.
AB  - The characterization of a dielectrophoretic/gravitational field-flow
      fractionation (DEP/G-FFF) system using model polystyrene (PS) microbeads is
      presented. Separations of PS beads of different surface functionalization (COOH
      and none) and different sizes (6, 10, and 15 microm in diameter) are
      demonstrated. To investigate the factors influencing separation performance,
      particle elution times were determined as a function of particle suspension
      conductivity, fluid flow rate, and applied field frequency and voltage.
      Experimental data were analyzed using a previously reported theoretical model and
      good agreement between theory and experiment was found. It was shown that
      separation of PS beads was based on the differences in their effective dielectric
      properties. Particles possessing different dielectric properties were positioned
      at different heights in a fluid-flow profile in a thin chamber by the balance of
      DEP and gravitational forces, transported at different velocities under the
      influence of the fluid flow, and thereby separated. To explore hydrodynamic (HD)
      lift effects, velocities of PS beads were determined as a function of fluid flow
      rate in the separation chamber when no DEP field was applied. In this case,
      particle equilibrium height positions were governed solely by the balance of HD
      lift and gravitational forces. It was concluded that under the experimental
      conditions reported here, the DEP force was the dominant factor in controlling
      particle equilibrium height and that HD lift force played little role in DEP/G
      FFF operation. Finally, the influence of various experimental parameters on
      separation performance was discussed for the optimization of DEP/G-FFF.

PMID- 9591695
TI  - A continuous-flow capillary mixing method to monitor reactions on the microsecond
      time scale.
AB  - A continuous-flow capillary mixing apparatus, based on the original design of
      Regenfuss et al. (Regenfuss, P., R. M. Clegg, M. J. Fulwyler, F. J. Barrantes,
      and T. M. Jovin. 1985. Rev. Sci. Instrum. 56:283-290), has been developed with
      significant advances in mixer design, detection method and data analysis. To
      overcome the problems associated with the free-flowing jet used for observation
      in the original design (instability, optical artifacts due to scattering, poor
      definition of the geometry), the solution emerging from the capillary is injected
      directly into a flow-cell joined to the tip of the outer capillary via a ground
      glass joint. The reaction kinetics are followed by measuring fluorescence versus
      distance downstream from the mixer, using an Hg(Xe) arc lamp for excitation and a
      digital camera with a UV-sensitized CCD detector for detection. Test reactions
      involving fluorescent dyes indicate that mixing is completed within 15 micros of
      its initiation and that the dead time of the measurement is 45 +/- 5 micros,
      which represents a >30-fold improvement in time resolution over conventional
      stopped-flow instruments. The high sensitivity and linearity of the CCD camera
      have been instrumental in obtaining artifact-free kinetic data over the time
      window from approximately 45 micros to a few milliseconds with signal-to-noise
      levels comparable to those of conventional methods. The scope of the method is
      discussed and illustrated with an example of a protein folding reaction.

PMID- 9591694
TI  - Quantitative fluorescence resonance energy transfer measurements using
      fluorescence microscopy.
AB  - Fluorescence resonance energy transfer (FRET) is a technique used for quantifying
      the distance between two molecules conjugated to different fluorophores. By
      combining optical microscopy with FRET it is possible to obtain quantitative
      temporal and spatial information about the binding and interaction of proteins,
      lipids, enzymes, DNA, and RNA in vivo. In conjunction with the recent development
      of a variety of mutant green fluorescent proteins (mtGFPs), FRET microscopy
      provides the potential to measure the interaction of intracellular molecular
      species in intact living cells where the donor and acceptor fluorophores are
      actually part of the molecules themselves. However, steady-state FRET microscopy
      measurements can suffer from several sources of distortion, which need to be
      corrected. These include direct excitation of the acceptor at the donor
      excitation wavelengths and the dependence of FRET on the concentration of
      acceptor. We present a simple method for the analysis of FRET data obtained with
      standard filter sets in a fluorescence microscope. This method is corrected for
      cross talk (any detection of donor fluorescence with the acceptor emission filter
      and any detection of acceptor fluorescence with the donor emission filter), and
      for the dependence of FRET on the concentrations of the donor and acceptor.
      Measurements of the interaction of the proteins Bcl-2 and Beclin (a recently
      identified Bcl-2 interacting protein located on chromosome 17q21), are shown to
      document the accuracy of this approach for correction of donor and acceptor
      concentrations, and cross talk between the different filter units.

PMID- 9591696
TI  - Monte Carlo analysis of obstructed diffusion in three dimensions: application to
      molecular diffusion in organelles.
AB  - Molecular transport in the aqueous lumen of organelles involves diffusion in a
      confined compartment with complex geometry. Monte Carlo simulations of particle
      diffusion in three dimensions were carried out to evaluate the influence of
      organelle structure on diffusive transport and to relate experimental
      photobleaching data to intrinsic diffusion coefficients. Two organelle structures
      were modeled: a mitochondria-like long closed cylinder containing fixed luminal
      obstructions of variable number and size, and an endoplasmic reticulum-like
      network of interconnected cylinders of variable diameter and density.
      Trajectories were computed in each simulation for >10(5) particles, generally for
      >10(5) time steps. Computed time-dependent concentration profiles agreed
      quantitatively with analytical solutions of the diffusion equation for simple
      geometries. For mitochondria-like cylinders, significant slowing of diffusion
      required large or wide single obstacles, or multiple obstacles. In simulated spot
      photobleaching experiments, a approximately 25% decrease in apparent diffusive
      transport rate (defined by the time to 75% fluorescence recovery) was found for a
      single thin transverse obstacle occluding 93% of lumen area, a single 53%
      occluding obstacle of width 16 lattice points (8% of cylinder length), 10 equally
      spaced 53% obstacles alternately occluding opposite halves of the cylinder lumen,
      or particle binding to walls (with mean residence time = 10 time steps). Recovery
      curve shape with obstacles showed long tails indicating anomalous diffusion.
      Simulations also demonstrated the utility of measurement of fluorescence
      depletion at a spot distant from the bleach zone. For a reticulum-like network,
      particle diffusive transport was mildly reduced from that in unobstructed three
      dimensional space. In simulated photobleaching experiments, apparent diffusive
      transport was decreased by 39-60% in reticular structures in which 90-97% of
      space was occluded. These computations provide an approach to analyzing
      photobleaching data in terms of microscopic diffusive properties and support the
      paradigm that organellar barriers must be quite severe to seriously impede solute
      diffusion.

PMID- 9591698
TI  - Prognostic significance of cell cycle parameters in infiltrative ductal breast
      carcinoma.
AB  - Flow-cytometric DNA analysis was performed retrospectively from paraffin-embedded
      blocks in 158 consecutive ductal infiltrative breast carcinoma patients grades I
      III. Normal breast tissue was used as control. Tumor proliferative activity, cell
      ploidy, and DNA index (DI) were related to age of patients, histological grade of
      tumor, tumor size, axillary lymph node status, estrogen and progesterone receptor
      status, menopausal status,TNM clinical classification, and survival. There was a
      significant association between DNA aneuploidy and a high cellular proliferative
      activity, increased DI, poor differentiation of tumor, primary tumor size, number
      of positive lymph nodes, and postmenopausal state. Increased proportion of cells
      in S-phase was associated with positive lymph node status and higher number of
      positive lymph nodes. The cell cycle parameters had no prognostic value either
      for overall survival of disease-free survival of the patients.

PMID- 9591697
TI  - Mechanical properties of actin filament networks depend on preparation,
      polymerization conditions, and storage of actin monomers.
AB  - This study investigates possible sources for the variance of more than two orders
      of magnitude in the published values for the shear moduli of purified actin
      filaments. Two types of forced oscillatory rheometers used in some of our
      previous work agree within a factor of three for identical samples. Polymers
      assembled in EGTA and Mg2+ from fresh, gel-filtered ATP-actin at 1 mg/ml
      typically have an elastic storage modulus (G') of approximately 1 Pa at a
      deformation frequency of 0.1-1 Hz. G' is slightly higher when actin is
      polymerized in KCl with Ca2+ and Mg2+. Gel filtration removes minor contaminants
      from actin but has little effect on G' for most preparations of actin from
      acetone powder. Storage of actin monomers without frequent changes of buffer
      containing fresh ATP and dithiothreitol can result in changes that increase the
      G' of filaments by more than a factor of 10. Frozen storage can preserve the
      properties of monomeric actin, but care is necessary to prevent protein
      denaturation or aggregation due to freezing or thawing.

PMID- 9591699
TI  - Development of a new microparticle-enhanced turbidimetric assay for C-reactive
      protein with superior features in analytical sensitivity and dynamic range.
AB  - Novel assay techniques were applied to a newly developed microparticle-based
      assay for C-reactive protein (CRP). By using two different sized microparticles
      covalently coated with two monoclonal antibodies of different reactivity, high
      analytical sensitivity and a high upper measuring limit could be simultaneously
      attained, resulting in a remarkably wide dynamic range. This range was further
      increased by calculating the signal (reaction rate) optimally with a new software
      capability of COBAS INTEGRA, a clinical chemistry analyzer. The assay showed high
      precision between 2 mg/l and 160 mg/l with use of only 2.5 microl specimen. The
      detection limit was estimated as 0.3 mg/l CRP. The assay was four to eight times
      more sensitive and precise than existing turbidimetric or nephelometric assays
      with comparable upper measuring limits. The assay also showed good linearity and
      correlated well with commercial assays. This new microparticle-based CRP assay
      provides the accuracy and precision that are required to determine CRP at low
      concentrations where new clinical implications such as prognosis of
      cardiovascular diseases are envisaged. The assay's wide dynamic range will
      additionally lead to a reduction in the number of repeated analyses, thus
      improving the efficiency of CRP determinations in clinical laboratories.

PMID- 9591700
TI  - A proposal for standardizing urine collections for bone resorption markers
      measurement.
AB  - Diurnal variations in the excretion of bone resorption markers were assessed in
      order to identify the type of urine collection which provides the most
      information on bone resorption rate and its relation to measuring bone dynamics
      in a postmenopausal population. Sixty women, ages 43-67 and without disease or
      treatment known to affect bone mineral density, were divided into two groups on
      the basis of femoral mineral density T-score: <1.5 (Group I), >1.5 (Group II).
      Bone formation was assessed by measuring bone alkaline phosphatase activity and
      osteocalcin concentration, bone resorption by urinary hydroxyproline,
      pyridinoline and deoxypiridinoline, N-telopeptide, galactosyl hydroxylysine, and
      CrossLaps. To identify the more appropriate collection times, urine samples were
      collected from 7 am to 3 pm; from 3 pm to 11 pm; from 11 pm to 7 am. Twenty-four
      hour urine collection and first morning void urine samples were also measured.
      The findings suggest that nocturnal collection and first morning void samples
      provide the most reliable data on the rate of bone degradation, possibly showing
      bone loss not only in osteopenic patients but also in women with a low T-score.
      Nocturnal and first morning samples should therefore be recommended in order to
      standardize sample collection, as they enable an accurate assessment of bone
      resorption markers and improved comparability to results from different studies,
      as well as a less cumbersome collection modality.

PMID- 9591701
TI  - Immunohistochemical detection of MUC2 mucin core protein in ulcerative colitis.
AB  - MUC2 mucin is predominantly expressed in the colon and is considered to play an
      important role in the protection of that organ. Recent findings suggested that
      MUC2 protein levels are significantly decreased in active ulcerative colitis
      (UC). We therefore performed an immunohistochemical study to reveal if the
      expression of MUC2 protein is altered in UC. Seventy-nine biopsy tissue specimens
      from 31 UC patients, along with normal colon tissues, were immunostained with
      anti-MUC2 mucin core protein monoclonal antibody (MoAb) CCP58 (IgG1). UC tissue
      specimens were divided into two groups based on the histological severity of
      inflammation, i.e., 64 with active inflammation (grades 2-5) and 15 without
      (grade 1). In the former group, 52 out of 64 (81.3%) tissue specimens contained
      sections of glands with a few cells positive for MoAb CCP58. These glands were
      small and consisted of MUC2 negative-short cells and a few positive cells without
      apparent mucus formation, considered to be immature regenerative glands. In
      contrast, the staining pattern was almost the same as that of the normal colon
      and no immature glands were seen in the group without active inflammation. The
      sections of immature regenerative glands with a few MUC2-positive cells were
      exclusively found in the UC tissues with active inflammation, but not in those
      without it, suggesting that the expression of MUC2 protein may be decreased in
      active UC.

PMID- 9591702
TI  - Potential of the immune complex transfer enzyme immunoassay for antigens and
      antibodies to improve the sensitivity and its limitations.
AB  - In order to reduce the nonspecific signal of noncompetitive solid phase
      immunoassays and to improve their sensitivities, the immune complex transfer
      enzyme immunoassay has been developed. Antigens to be measured were reacted with
      2,4-dinitrophenyl-biotinyl-antibody Fab' and antibody Fab'-beta-D-galactosidase
      conjugate, and antibody IgGs to be measured were reacted with 2,4-dinitrophenyl
      antigen and antigen-beta-D-galactosidase conjugate. The immune complexes formed
      comprising the three components were trapped onto colored polystyrene beads
      coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG. After washing,
      the immune complexes were eluted from the colored polystyrene beads with epsilonN
      2,4-dinitrophenyl-L-lysine, and the eluates were incubated with white polystyrene
      beads coated with streptavidin for antigens and coated with affinity-purified
      (anti-human IgG gamma-chain) IgG for antibody IgGs to transfer the immune
      complexes. By this method, ultrasensitive enzyme immunoassays have been developed
      for HIV-1 p24 antigen and antibody IgGs to HIV-1 p17 and reverse transcriptase
      (RT). The nonspecific signals in the absence of the antigen and the antibody IgGs
      were reduced 300 to 15,000-fold by the immune complex transfer process, but the
      amounts of the immune complexes decreased only 1.8 to 3.1-fold by the immune
      complex transfer. As a result, the sensitivities for HIV-1 p24 antigen and
      antibody IgGs to HIV-1 p17 and RT were improved 100 to 5,600-fold by the immune
      complex transfer. The detection limit of HIV-1 p24 antigen by 20 hr assay of beta
      D-galactosidase activity (10 zmol) was 4,000 to 17,000-fold lower than those
      obtained with currently available commercial kits. The improved sensitivities for
      antibody IgGs to p17 and RT by 20 hr assay of beta-D-galactosidase activity were
      1 x 10(5) to 3 x 10(5)-fold higher than those of Western blotting for p17 and p66
      bands. However, the nonspecific signals in the absence of antigens and antibody
      IgGs were enhanced to various degrees by two factors. In order to transfer the
      immune complexes more efficiently within shorter periods of time, the colored
      polystyrene beads were incubated with the white polystyrene beads in the presence
      of epsilonN-2,4-dinitrophenyl-L-lysine. Such direct contact between solid phases
      for trapping and transferring of the immune complexes significantly enhanced the
      nonspecific signals. In addition, the presence of human serum samples containing
      neither antigens to be measured nor antibody IgGs to be measured also enhanced
      the nonspecific signals to various extents. Namely, these two factors limited the
      effect of the immune complex transfer to improve the sensitivity by 20 hr assay
      of beta-D-galactosidase activity. By 1 hr assay of beta-D-galactosidase activity,
      the detection limit of HIV-1 p24 antigen using 10 microl of serum samples (0.24
      pg/ml) was 40 to 80-fold lower than those obtained with currently available
      commercial kits using 100 to 200 microl of serum samples (10 to 20 pg/ml) and the
      detection limits of antibody IgGs to HIV-1 pl7 and RTwere 1 x 10(4) to 3 x 10(4)
      fold lower than those by Western blotting for p17 and p66 bands. Finally, the
      immunoreactions involved in the immune complex transfer enzyme immunoassays--the
      formation, trapping, and transferring of the immune complexes--will be performed
      within 15 to 30 min.

PMID- 9591703
TI  - Frequent clonal expansion of peripheral T cells in patients with autoimmune
      diseases: a novel detecting system possibly applicable to laboratory examination.
AB  - To investigate T cell involvement in antigen-specific immune responses, it is
      important to detect accumulating T cells at a clonal level in vivo. However, thus
      far the clinical application of such analyses has been limited. Here we have
      established novel primers to anneal with T cell receptor (TCR) beta genes of
      multiple Vbeta families and applied them to reverse transcription-polymerase
      chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis to
      evaluate peripheral T cell clonality of autoimmune disease patients. As a result,
      the new Vbeta primers could detect accumulating T cell clones in the periphery of
      healthy individuals and patients. It was revealed that patients with autoimmune
      diseases such as systemic lupus erythematosus (SLE) had a larger number of clonal
      accumulations of peripheral T cells compared with normal individuals. Thus, the
      RT-PCR-SSCP system using the new multifamily Vbeta primers is the first such
      laboratory examination to detect T cell clonal expansion, and will provide a
      simple and sensitive tool to aid in the diagnosis and also in the investigation
      of the pathogenesis of autoimmune diseases.

PMID- 9591704
TI  - Using 2-step PCR and restriction endonuclease digestion to detect K-ras mutation
      in paraffin-embedded tissues: is it reliable?
AB  - In this study, we detected the existence of both wild type and mutant K-ras DNA
      on the cutting board and in the solutions for tissue processing in our pathology
      laboratory. The detection rate of K-ras mutant DNA inversely correlated with the
      frequency of the solution changed, implying that DNA contaminant including K-ras
      mutant may be accumulated while increasing specimens were processed. The exact
      routes of contamination during tissue processing remain to be determined.
      Nevertheless, this study unveils the possibility of DNA contamination in the
      laboratory that can be amplified by PCR analysis, and precaution should be taken
      while we interpret our PCR data from paraffin-embedded specimens. The work also
      highlights the necessity of contamination control procedures, including specific
      laboratory construction, environmental control, and strict hygiene standards for
      laboratory equipment and personnel. Moreover, fresh specimens seem more reliable
      than archival materials for PCR diagnosis.

PMID- 9591705
TI  - Changes in morphology of neuroblastoma cells treated with all-trans retinoic acid
      combined with transfer of the C-terminal region of the amyloid precursor protein.
AB  - Alzheimer disease is a progressive neurodegenerative disorder that is
      characterized by a loss of cognitive and memory functions. Amyloid fibrils
      deposited in neuritic plaque is mainly beta-amyloid protein (Abeta) that is
      derived from amyloid precursor protein (APP). The secreted form of APP, which is
      corresponded to N-terminal portion of APP, shows neurotrophic activities. On the
      other hand, Abeta and cytoplasmic domains of APP are thought to be neurotoxic. In
      order to investigate the effect of C-terminal fragment of APP covering Abeta and
      the cytoplasmic domain upon cell growth and differentiation, we established a
      stably transfected cell line producing the C-terminal 100 amino acid peptide of
      APR The transfected clones stained positively with anti-Abeta monoclonal
      antibody, TB-1. The growth rate of the transfected cells was not significantly
      different from that of mock-transfected cells or native NB39 cells. After
      treatment with all-trans retinoic acid (ATRA), mock-transfected cells extended
      neurite processes and showed neuronal-like differentiation, while a transfected
      clone overexpressing C-terminal fragment did not present neuronal-like
      morphology. These results suggest that ATRA-induced neurite extension may be
      suppressed by overexpression of the C-terminal fragment of APP.

PMID- 9591706
TI  - Ultrasensitive and rapid enzyme immunoassay (thin aqueous layer immune complex
      transfer enzyme immunoassay) for antibody IgG to HIV-1 p17 antigen.
AB  - The immune complex transfer enzyme immunoassay for antibody IgG to HIV-1 p17
      antigen was performed in two different ways (the present immunoassays I and II)
      within shorter periods of time than previously reported. In the present
      (simultaneous) immunoassay I, antibody IgG to HIV-1 p17 antigen in 10 microL of
      serum samples was incubated simultaneously with 2,4-dinitrophenyl-maltose binding
      protein-recombinant p17(rp17) fusion protein and rp17-beta-D-galactosidase
      conjugate in a total volume of 22 microL for 10 min to form the immune complex
      comprising the three components. The reaction mixture was incubated with a
      polystyrene bead of 6.35 mm in diameter coated with affinity-purified (anti-2,4
      dinitrophenyl group) IgG for 5 min in a styrol test tube (13.3 x 54 mm and 2.1 g)
      to trap the immune complex. After washing, the polystyrene bead was incubated
      with 30 microL of epsilonN-2,4-dinitrophenyl-L-lysine solution in a polystyrene
      tube (12 x 75 mm) coated with affinity-purified (antihuman IgG gamma-chain) IgG
      for 10 min to transfer the immune complex. In the present (sequential)
      immunoassay 11, a polystyrene bead of 6.35 mm in diameter coated successively
      with affinity-purified (anti-2,4-dinitrophenyl group) IgG and 2,4-dinitrophenyl
      maltose binding protein-rp17 fusion protein was incubated in a styrol test tube
      (13.3 x 54 mm and 2.1 g) sequentially with antibody IgG to HIV-1 p17 antigen in
      10 microL of serum samples in a total volume of 16 microL for 5 min and
      subsequently with rp17-beta-D-galactosidase conjugate in a volume of 10 microL
      for 5 and 10 min. The immune complex formed on the polystyrene bead was
      transferred to a polystyrene tube coated with affinity-purified (antihuman IgG
      gamma-chain) IgG for 5 and 10 min in the same way as in the present immunoassay
      I. During the incubations, the styrol test tubes containing the polystyrene beads
      and reaction mixtures were shaken, and the polystyrene test tubes were rotated
      with shaking, so that the polystyrene beads were rotated randomly, and small
      drops (16 to 30 microL) of the reaction mixtures evenly contacted all parts of
      the solid phase surfaces during the incubations, though only small parts of the
      solid phase surfaces were contacted at one time. The intent was to continuously
      mix thin aqueous layers of the reaction mixtures covering the solid phase
      surfaces with the rest of the reaction mixtures. (Therefore, these immunoassays
      were called thin aqueous layer immunoassays.) beta-D-Galactosidase activity bound
      to the polystyrene tubes was assayed by fluorometry for 30 and 60 min. The
      present immunoassays I and II, in which only 15 to 25 min were used for the
      immunoreactions, were as sensitive if not more so than the previous immune
      complex transfer enzyme immunoassay requiring 150 min for the immunoreactions. In
      these earlier immunoreactions, the immune complex comprising the three components
      formed by 30 min incubation was trapped onto two polystyrene beads (3.2 mm in
      diameter) coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG for 60
      min, and was then transferred to two polystyrene beads (3.2 mm in diameter)
      coated with affinity-purified (antihuman IgG y-chain) IgG for 60 min in a total
      volume of 150 microL. Furthermore, the present (sequential) immunoassay 11 (and
      probably I) could become approximately 10 times more sensitive by assaying bound
      beta-D-galactosidase activity for a longer period of time (10 h), since beta-D
      galactosidase activity, bound nonspecifically in the presence of serum samples
      from HIV-1 seronegative subjects, was considerably low.

PMID- 9591707
TI  - Concerning the anti-major histocompatibility complex approach to HIV type 1
      vaccine design.

PMID- 9591708
TI  - Phase I study of a human monoclonal antibody directed against the CD4-binding
      site of HIV type 1 glycoprotein 120.
AB  - A phase I dose escalation study was conducted with the human monoclonal anti
      gp120 antibody F105, to evaluate the safety, pharmacokinetics, and functional
      activity of F105 in HIV-1-infected individuals. F105 is an IgG1(kappa) antibody
      reactive with a discontinuous epitope that overlaps the CD4-binding site of
      gp120. F105 neutralizes laboratory strains of HIV-1 and some primary isolates,
      and synergizes with other antibodies in neutralizing an expanded spectrum of
      isolates. Four patients each with CD4 counts between 200 and 500/mm3 received a
      single dose of F105 at 100 or 500 mg/m2, intravenously. Sustained levels of F105
      were obtained in plasma, and there was no evidence of an immune response to F105
      as determined by a double-antigen immunoassay. No patient experienced any
      toxicity. Infused antibody retained full functional activity as detected by the
      ability of sera to block the binding of labeled F105 to HIV-1-infected cells. Of
      note, all patients had preexisting antibody to the gp120 CD4-binding site. The
      ability to culture virus by quantitative microculture remained unchanged by this
      single dose of antibody. Thus, it can be concluded that F105 is safe and nontoxic
      as a single injection at the doses tested. Furthermore, the antibody retains full
      gp120-binding activity. In these patients, with preexisting CD4-binding site
      antibody, there is no evidence of anti-HIV-1 activity following a single antibody
      infusion.

PMID- 9591709
TI  - A pilot clinical trial of HIV antigen-pulsed allogeneic and autologous dendritic
      cell therapy in HIV-infected patients.
AB  - A pilot study was carried out to assess the safety and antigen-presenting
      properties of allogeneic or autologous dendritic cells (DCs) in six HLA-A2+, HIV
      infected patients. Allogeneic DCs obtained from the peripheral blood of HLA
      identical, HIV-seronegative siblings were pulsed with recombinant HIV-1 MN gp160
      or synthetic peptides corresponding to HLA-A2-restricted cytotoxic epitopes of
      envelope, Gag, and Pol proteins. The antigen-pulsed cells were infused
      intravenously six to nine times at monthly intervals and HIV-specific immune
      responses were monitored. One allogeneic DC recipient with a CD4+ T cell count of
      460/mm3 showed increases in envelope-specific CTL- and lymphocyte-proliferative
      responses, as well as in IFN-gamma and IL-2 production. Another allogeneic DC
      recipient with a CD4+ T cell count of 434/mm3 also showed an increase in HIV
      envelope-specific lymphocyte-proliferative responses. A recipient of autologous
      DCs with a CD4+ T cell count of 730/mm3 showed an increase in peptide-specific
      lymphocyte-proliferative responses after three infusions. Three other allogeneic
      DC recipients with CD4+ T cell counts <410/mm3 did not show increases in their
      HIV-specific immune responses. No clinically significant adverse effects were
      noted in this study and CD4+ T cell numbers and plasma HIV-1 RNA detected by RT
      PCR of all six patients were stable during the study period. Thus, both
      allogeneic and autologous DC infusions were well tolerated and in patients with
      normal or near normal CD4+ T cell counts administration of these antigen-pulsed
      cells enhanced the immune response to HIV. However, since no effect on viral load
      was observed there was no evidence that this approach provided clinical benefit.

PMID- 9591710
TI  - Changes in CD4+ and CD8+ T cell subsets in response to highly active
      antiretroviral therapy in HIV type 1-infected patients with prior protease
      inhibitor experience.
AB  - This study explores whether previous failures on antiretroviral drug regimens
      preclude the possibility of immune restoration. This was assessed by evaluating T
      cell subset changes in individuals who received a salvage regimen of highly
      active antiretroviral therapy (HAART) after initially failing protease inhibitor
      monotherapy. Ten HIV-1-infected asymptomatic patients received a regimen of
      indinavir, zidovudine, and 3TC after failing saquinavir monotherapy. Changes in
      absolute numbers of naive, memory, and activated CD4+ and CD8+ T cells expressing
      a selection of CD45RA, CD62L, CD45RO, HLA-DR, and CD38 markers were monitored
      prospectively over 6 months. These measurements were correlated with plasma viral
      load along with alterations in a selected CD8+ V alpha/Vbeta T cell receptor
      (TCR) repertoire. Over 6 months there was a progressive increase in numbers of
      CD4+ memory (CD45RA-CD62L+) and naive (CD45RA+CD62L+) T cells, which displayed a
      modest inverse correlation with viral load. Two phases of CD8+ memory cell
      changes were identified, consisting of a transient increase in CD45RA+CD62L-
      numbers after 2 months and thereafter a progressive rise in CD45RA-CD62L+ cells
      until 6 months. A strong correlation existed between reduced viral load and loss
      of activated CD8+CD38+HLA-DR+ cell numbers. There was also a temporary broadening
      of the CD8+ V alpha/Vbeta TCR repertoire at 8 weeks, which became skewed after 6
      months in parallel with reduced viral suppression. Closer analysis of naive and
      memory cell subset proportions in individual patients revealed that enlarged
      pools of naive subsets were evident in those patients with rebounds in viral
      load. Overall, drug-experienced patients responding to HAART displayed increased
      numbers of naive and memory CD4+ subsets, and reduced CD8+ cell activation with a
      loss of TCR skewing.

PMID- 9591711
TI  - Plasma virus load evaluation in relation to disease progression in HIV-infected
      children.
AB  - The objective of this study was to investigate the relationship of plasma HIV RNA
      load with survival and disease progression in HIV-infected children and to
      determine its correlation with cellular HIV DNA. Virus load (VL, HIV RNA
      copies/ml) was determined retrospectively by nucleic acid sequence-based
      amplification (NASBA) assay in 144 stored plasma samples between birth and 48
      months in 50 children of whom 40 are alive (age range, 2-13 years). On the basis
      of clinical and immunologic status children were classified as rapid progressors
      (RPs), or nonrapid progressors (NRPs). Proviral HIV DNA quantitated by QC-PCR
      (quantitative competitive polymerase chain reaction) in 24 children was compared
      with plasma HIV RNA. At age <3 months, plasma VL <750,000 copies/ml was
      associated with significantly higher survival to age >2 years (p < or =0.01)
      compared with a VL of > or =750,000 copies/ml. Increasing mortality was observed
      with increasing plasma HIV RNA levels at ages 3-24 months and baseline VL of
      infants who died before age 24 months was significantly higher (p = 0.004) than
      baseline VL of those who survived beyond 24 months. Although baseline VL in
      infants classified as RPs was higher than that of NRPs, the difference was not
      statistically significant. Among surviving children 2-13 years of age, the
      baseline VL obtained at <24 months of age was not predictive of disease severity.
      Although no significant correlation was noted between plasma HIV RNA and proviral
      DNA, the concurrence of positive and negative results was >80%. We conclude that
      high plasma HIV RNA in infancy is associated with increased mortality.

PMID- 9591712
TI  - Association of antibody reactivity to ELDKWA, a glycoprotein 41 neutralization
      epitope, with disease progression in children perinatally infected with HIV type
      1.
AB  - The association between antibody reactivity to the neutralizing epitope ELDKWA in
      the transmembrane glycoprotein gp41 and disease progression was investigated in
      29 children perinatally infected with HIV-1. Levels of antibody reactivity to
      this epitope, measured over time, were associated with absolute CD4+ lymphocyte
      numbers and disease status, and inversely associated with the levels of acid
      dissociated p24 antigen in the plasma. Early virus isolates from 10 of 12
      children with no detectable antibody reactivity to this epitope were sequenced.
      Only three contained sequences that differed from the consensus, indicating that
      this epitope is well conserved in this population. None of these three children
      developed antibodies to the autologous sequences, indicating that at least 80% of
      children with negative antibody reactivity to this epitope were true
      nonresponders. Together, these results indicate that the ELDKWA determinant could
      be an important component in the formulation of a vaccine or for
      immunotherapeutic approaches to HIV-1 infection.

PMID- 9591713
TI  - Interactions of polyclonal and monoclonal anti-glycoprotein 120 antibodies with
      oligomeric glycoprotein 120-glycoprotein 41 complexes of a primary HIV type 1
      isolate: relationship to neutralization.
AB  - We have studied antibody reactivity with monomeric and oligomeric forms of the
      gp120 envelope glycoprotein from the macrophage-tropic primary virus, HIV-1 JR
      FL. We find that the correlation between oligomer reactivity and virus
      neutralization is not absolute for MAbs to epitopes overlapping the CD4-binding
      site on gp120. An MAb (205-46-9) with very limited neutralizing ability for JR-FL
      binds about as avidly to oligomeric JR-FL envelope glycoproteins as the strongly
      neutralizing IgG1b12 MAb does. In addition, neutralizing and nonneutralizing sera
      from HIV-1-infected people are similar in their reactivities to oligomeric JR-FL
      envelope glycoproteins; the correlation between oligomer reactivity and virus
      neutralization is weak. Although oligomer reactivity of an anti-gp120 antibody is
      necessary for virus neutralization, it is not always sufficient to cause it.

PMID- 9591714
TI  - Natural IgM antibodies in baby rabbit serum bind high-mannose glycans on HIV type
      1 glycoprotein 120/160 and activate classic complement pathway.
AB  - Serum from rodents and felines has been found very effective in complement
      dependent lysis of HIV-1, even in nonimmunized animals, but the effector
      molecules in animal serum and target structures on HIV-1 envelope gp120/160
      responsible for complement activation were not determined. We have found that the
      natural anti-carbohydrate-specific IgM antibodies present in baby rabbit serum
      were able to lyse effectively the CD4+ T cells coated with the whole virus or
      with a recombinant gp120/160, irrespectively of the virus strain or glycoprotein
      expression system. When the high mannose-type glycans on gp160 were enzymatically
      removed by endoglycosidase F or blocked with the specific lectins, the complement
      activation and subsequent cell lysis were abolished. IgM-depleted baby rabbit
      serum was not able to lyse the gp120/160- and/or whole virus-coated target cells.
      These results suggest that the target structures for complement-activating and
      naturally occurring IgM antibodies in baby rabbit serum are high-mannose residues
      on HIV-1 envelope glycoprotein.

PMID- 9591715
TI  - Expression patterns of the HIV type 1 coreceptors CCR5 and CXCR4 on CD4+ T cells
      and monocytes from cord and adult blood.
AB  - We have measured the surface expression of the HIV-1 coreceptors CCR5 and CXCR4
      on CD4+ T cells and monocytes from cord and adult blood. The expression of CCR5
      was largely restricted to the memory (CD45RAlow) subset, whereas CXCR4 was
      expressed on both memory and naive (CD45RAhigh) T cells. The paucity of memory
      CD4+ T cells in cord blood means that CCR5-positive cells are relatively
      uncommon, so the overall extent of CCR5 expression was reduced in cord blood,
      compared with adult blood. IL-2 activation of CD4+ T cells from both cord and
      adult bloods caused a substantial increase in CCR5 expression, but moderately
      decreased CXCR4 expression. PHA stimulation increased CCR5 expression slightly,
      but only on naive cells. Monocytes expressed both CCR5 and CXCR4 at levels that
      differed little between cord and adult blood.

PMID- 9591716
TI  - Induction of MHC-IIDR expression on circulating CD8+ lymphocytes in macaques
      infected with SIVmac239 nef-open but not with its nef-deletion mutant.
AB  - We examined the expression kinetics of activation antigens CD38 and MHC-IIDR (DR)
      on circulating CD8+ lymphocytes in rhesus macaques infected with pathogenic
      simian immunodeficiency virus strain SIVmac239 nef-open (239) or its
      nonpathogenic nef-deletion mutant (delta nef). In the longitudinal study, we
      found for the first time the induction of DR expression on CD8+ lymphocytes in
      239-infected macaques. The induction of DR was in parallel with an increasing
      viral load and a decreasing CD4+ lymphocyte level. In the macaques with the high
      viral load and low CD4 level, a considerable proportion of the DR+CD8+
      subpopulation was CD69+, indicating an activated state. On the other hand, no
      significant increase in the DR+CD8+ subpopulation level was observed in delta nef
      infected macaques. These data indicate that the evaluation of activation markers
      such as DR and/or CD69 on circulating CD8+ cells may be valuable as a surrogate
      marker in the SIV-macaque model.

PMID- 9591717
TI  - Traditional approach preventive HIV vaccines: What are the cell substrate and
      inactivation issues?
AB  - A workshop was convened to discuss safety issues for traditional-approach HIV
      vaccines, especially inactivated vaccines. The topics included issues pertaining
      to (1) cell substrates used for production and (2) vaccine virus inactivation.
      The use of cell substrates such as tumor-derived continuous cell lines (TCLs) or
      virus-transformed. CLs may be the most feasible approach to provide commercial
      scale virus yields. However, especially because of concerns about tumorigenicity,
      TCLs have not been used to produce preventive vaccines for human trials with
      healthy subjects in the United States. Residual TCL material (e.g., DNA, cellular
      proteins, viruses) may not be removed during purification of intact HIV virions
      to the same extent achievable for a recombinant protein. Manufacturing processes,
      e.g., physicochemical methods of destroying DNA, could decrease tumorigenicity
      risk. Methods to assess potential for tumorigenicity may need further
      development. Another potential substrate for viral production that merits further
      study is human peripheral blood mononuclear cells (PBMCs). Regardless of the cell
      substrate used, extensive testing for adventitious agents (including non-HIV
      retroviruses) is needed. Vaccine virus inactivation can be considered in
      statistical terms, i.e., the probability of a surviving infectious particle. One
      formula to determine a "safety margin" (SM) is reduction of titer in log10 for
      all inactivation steps minus initial viral infectivity in log10. Calculations for
      appropriate SMs should include all sources of variability (e.g., lot-to-lot
      differences). Ensuring a specified SM, as the lower bound of the 95% confidence
      interval, for production lots was discussed. Sensitivity and specificity of
      infectivity assays may present limitations.

PMID- 9591718
TI  - Epidemic expansion of HIV type 1 subtype C and recombinant genotypes in Tanzania.

PMID- 9591719
TI  - New widespread CXCR4 allele in rhesus macaques does not predict subspecies or
      clinical evolution.

PMID- 9591720
TI  - Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of
      tumors showing perivascular myoid differentiation.
AB  - The clinicopathologic features of 24 tumors showing perivascular myoid
      differentiation are described. These included tumors with histologic features of
      "infantile-type" myofibromatosis occurring in adult patients (8 cases), tumors
      with composite features of "hemangiopericytoma" and glomus tumor (9 cases), and
      tumors with a distinctive concentric perivascular proliferation of spindle cells
      (7 cases). Evidence of morphologic overlap among these groups suggests they are
      closely related neoplasms that form a single spectrum. Age of patients with
      lesions resembling infantile-type myofibromatosis ranged from 23 to 67 years
      (median, 37 years). Clinicopathologic manifestations of this disease included
      multicentricity (4 cases), local recurrence (3 cases), persistence of congenital
      lesions into adulthood (4 cases), and tumors that were multifocal within the
      confines of one anatomic region (7 cases). Histologically, all cases showed a
      biphasic pattern that consisted of fascicles of spindle cells with abundant
      eosinophilic cytoplasm that resembled smooth muscle, in addition to a population
      of more primitive spindled cells associated with a hemangiopericytomalike
      vascular pattern. Six cases showed reversal of the typical zonation seen in
      pediatric cases in that the primitive component surrounded the more mature
      fascicular areas. Also described are nine tumors with features that are
      intermediate between glomus tumor and hemangiopericytoma, which we have
      designated glomangiopericytoma. These tumors are characterized by prominent
      branching vessels lined by a single row of endothelial cells surrounded by
      epithelioid cells with a glomoid appearance. In other areas, the tumors showed
      typical hemangiopericytomatous foci similar to those in the myofibromatosis
      cases. The principal points of distinction were a lack of myoid nodules and an
      absence of small primitive cells with basophilic cytoplasm. Ages of these
      patients ranged from 17 to 78 years (median, 35 years). All tumors were located
      in the subcutaneous tissue and the superficial soft tissue of the extremities.
      Recurrence developed in one of six patients with follow-up information. The
      recurrent tumor had features of angiomatoid malignant fibrous histiocytoma.
      Finally, we describe a subset of tumors characterized by concentric periluminal
      proliferation of bland, round to ovoid cells, which we have designated as
      myopericytoma. Patient age ranged from 10 to 66 years (median, 40 years). All
      were located in subcutaneous and superficial soft tissue of distal extremities.
      One patient had two recurrences in 3 years after initial excision. Our study
      suggests that these three lesional groups comprise a histologic continuum of
      tumors that share clinical similarities and that, perhaps, are designated more
      appropriately as perivascular myomas. The relationship of this family of tumors
      to so-called hemangiopericytoma is discussed.

PMID- 9591722
TI  - Intraoperative confirmation of parathyroid tissue during parathyroid exploration:
      a retrospective evaluation of the frozen section.
AB  - Although the frozen section is widely used to identify tissue type during
      parathyroid exploration in patients with hyperparathyroidism, questions regarding
      its accuracy have been raised. Frozen section error has been identified as a
      significant factor contributing to surgical failure. The purpose of this study
      was to establish the accuracy of frozen section in this setting and to identify
      pitfalls underlying frozen section error. The final pathologic diagnoses were
      compared with the paired frozen section diagnoses for all patients who underwent
      parathyroid exploration at this institution in the period between 1984 and 1997.
      For those cases in which a discrepancy was identified, the original
      histopathology slides and the medical records were reviewed. Of the 1579 frozen
      sections, a definitive and accurate diagnosis could not be determined in 20 cases
      (1.3%); in 7 (0.4%), the frozen section diagnosis was deferred, and in the other
      13 cases, the frozen section diagnosis was incorrect. Overall accuracy rate was
      99.2% after deferred cases were excluded. Frozen section artifact, sampling
      error, and judgmental error contributed to deferred or incorrect diagnoses.
      Several features confounded the distinction between parathyroid and thyroid
      tissue in 10 cases: the coexistence of parathyroid and nodular thyroid disease;
      intrathyroidal parathyroid glands showing conspicuous follicle formations or
      abundant oncocytic cells; and thyroid nodules with fatty stroma. The frozen
      section is a highly reliable means of identifying tissue type during parathyroid
      exploration. In exceptional cases, however, the distinction between parathyroid
      and thyroid tissue may not be possible owing to a striking overlap seen at the
      clinical, gross, and microscopic levels.

PMID- 9591721
TI  - Large cell neuroendocrine carcinoma of the lung: a histologic and
      immunohistochemical study of 22 cases.
AB  - Large cell neuroendocrine carcinoma (LCNEC) of the lung is defined as a poorly
      differentiated and high-grade neuroendocrine tumor that is morphologically and
      biologically between atypical carcinoid and small cell lung carcinoma (SCLC).
      During a survey concerning bcl-2 protein expression in the subtypes of lung
      cancer, we noticed that two previously diagnosed non-SCLCs met the criteria for
      LCNEC. Because LCNEC is a newly recognized clinicopathologic entity and because
      all reported cases have been retrieved from the so-called "neuroendocrine tumor
      file," we suspected that LCNEC had been underdiagnosed. In the present study, we
      histologically reviewed 766 surgically resected lung cancers and were able to
      diagnose 22 (2.87%) LCNECs with the neuroendocrine features subsequently
      confirmed by immunostaining for multiple neuroendocrine markers. Each case
      stained positively for at least three general neuroendocrine markers, and 12
      (54.5%) also were positive for neuroendocrine hormones. Histologically, most
      LCNECs showed a marked decrease in or a loss of organoid architecture and could
      be mistaken for poorly differentiated adenocarcinoma or squamous cell carcinoma.
      Because our LCNECs are the first to be identified by retrospective review of
      routinely diagnosed lung cancers, and 18 had been classified as non-SCLC, they
      may represent cases relatively difficult to diagnose. The present study shows
      that the most difficult diagnostic factor of LCNEC is the recognition of its
      light microscopic neuroendocrine features, and LCNEC must be distinguished not
      only from atypical carcinoid or SCLC, but also from common non-SCLC.
      Histologically, when an organoid architecture is subtle or absent, the
      rosettelike structure becomes the best marker for the recognition of
      neuroendocrine differentiation. Clinically, the prognosis for our LCNECs was
      significantly worse than that for stage-comparable non-SCLCs (p = 0.046).

PMID- 9591723
TI  - Peritumoral and nodal muciphages.
AB  - Three patients who underwent surgery for cancer showed Alcian blue positive cells
      in the sinusoids of the regional lymph nodes and, in one case, extensive
      infiltration in the soft tissues around the tumor. The cells contained variably
      sized vacuoles that occasionally indented the nuclei, imparting a signet-ringlike
      appearance. They were interpreted as muciphages based on morphology, reactivity
      with mucin stains, positive immunohistochemical staining for KP-1 and Mac-387,
      and negative staining for cytokeratin, S-100, and leukocyte common antigen (LCA).
      The material contained in these cells was Alcian blue positive at pH 2.5 and pH
      1, and was strongly periodic acid-Schiff positive after diastase digestion.
      Hyaluronidase only slightly reduced the intensity of the Alcian blue stain. These
      results indicate that the bulk of the material was epithelial-type mucin. To our
      knowledge, this is the first report of muciphages in lymph nodes. Careful
      attention to morphology and immunohistochemical findings is necessary to avoid
      confusion with metastatic or infiltrating signet ring or mucinous adenocarcinoma.

PMID- 9591725
TI  - Giant cell collagenoma: a benign dermal tumor with distinctive multinucleate
      cells.
AB  - We present five cases of a hitherto unreported cutaneous neoplasm. The tumors
      appeared as solitary slow-growing flesh-colored nodules arising in young and
      middle-aged adults. They were located on the trunk, the upper extremities, and
      the face, and did not recur after complete excision. Clinically, they were
      diagnosed as dermal nevus, Spitz's nevus, fibroma, or neurofibroma. Histology
      revealed polypoid flat-dome-shaped lesions with a sharply demarcated matrix
      consisting of coarse hyalinized collagen bundles arranged in a prominent
      storiform pattern and separated by mucin-containing clefts. Despite a low overall
      cellularity, the tumors contained numerous, occasionally bizarre-shaped,
      multinucleate giant cells with crowded vesicular nuclei and a pale staining foamy
      cytoplasm, as well as plump fibroblastlike cells with analogous nuclear
      morphology. Atypical nuclei or mitotic figures were not observed. The cells were
      strongly positive for vimentin but negative for cytokeratin, smooth muscle actin,
      desmin, S-100 protein, CD34, factor XIIIa, and the macrophage markers KP1, Mac
      387, and Ki-M1p, suggesting a fibroblastic origin. Based on the overall
      architecture, we conclude that these tumors probably represent a distinctive
      variant of solitary circumscribed storiform collagenoma (sclerotic fibroma) and
      propose the designation of giant cell collagenoma.

PMID- 9591724
TI  - Synaptophysin staining in normal brain: importance for diagnosis of
      ganglioglioma.
AB  - Neuronal and mixed glioneuronal tumors traditionally have comprised a very small
      percentage of intrinsic central nervous system neoplasms, although they are
      somewhat more common among juvenile brain tumors and in the temporal lobe.
      Neuronal differentiation increasingly is recognized in pleomorphic
      xanthoastrocytoma, intraventricular neurocytoma, and subependymal giant cell
      astrocytoma. However, the diagnostic distinctions between subtle ganglioglioma
      (with rare neurons) and infiltrating glioma with entrapped neurons and between
      infiltrating oligodendroglioma and parenchymal neurocytoma are problematic but
      may be clinically important. Recently, it was proposed that perisomatic
      synaptophysin immunostaining in the human central nervous system reliably and
      selectively discriminates neoplastic from nonneoplastic neurons. Using this
      criterion, the number of brain stem and spinal cord gangliogliomas could be
      increased substantially. We canvassed synaptophysin immunostaining patterns in
      the normal brain stem, cerebellum, and forebrain, and found that synaptophysin
      positive neurons are distributed broadly in the normal human brain. In disturbed
      neocortical tissue, such as near vascular malformations, synaptophysin-positive
      neurons and irregular white-matter synaptophysin immunostaining are visualized.
      Although synaptophysin-positive neurons are found in gangliogliomas and
      archipelagos of synaptophysin reactivity are found in neurocytomas, these
      patterns clearly are not pathognomonic for glioneuronal tumors and must be
      interpreted with caution whenever other histologic or ultrastructural evidence of
      neuronal differentiation is lacking.

PMID- 9591726
TI  - Keloidal dermatofibroma: report of 10 cases of a new variant.
AB  - Dermatofibroma is a common cutaneous tumor. Unusual variants of dermatofibroma
      that exhibit various epidermal changes or different cellular composition have
      been described. We observed 10 cases of a novel variant of dermatofibroma
      characterized by keloidal change within the tumor. Formalin-fixed, paraffin
      embedded tissues were used for histochemical and immunohistochemical studies. The
      patients consisted of six women and four men; median age was 34 years (17 to 59
      years). All tumors occurred on the extremities, and six were present for at least
      2 years. Tenderness was mentioned in four cases. They were described as
      erythematous or brown papules 1 cm or smaller. Clinical appearance did not
      deviate from that of ordinary dermatofibromas. Microscopically, the excised
      tumors showed a superficial circumscribed area of keloidal change under an
      atrophic epidermis in an otherwise ordinary dermatofibroma. In the keloidlike
      area, multinucleated giant cells, hemorrhage, hemosiderin deposits, and scattered
      KiM1P-positive histiocytes, but not factor XIIIa-positive or CD34-positive cells
      were present among the thick collagen fibers. There were no known recurrences.
      This variant dermatofibroma should not be overlooked as a simple keloidal scar.
      The observation of keloidal change in dermatofibromas may support the connotation
      that trauma is a possible cause of dermatofibroma. The fact that Asian people are
      more prone to develop keloid may have led us to find this new variant.

PMID- 9591727
TI  - Adenoid cystic carcinoma of the breast: value of histologic grading and
      proliferative activity.
AB  - Adenoid cystic carcinoma of the breast is an uncommon carcinoma with a
      distinctive histology. Prognosis is favorable, although recurrence and distant
      metastases have been described. We assessed whether histologic features and
      proliferative activity can identify aggressive neoplasms. We studied 31 cases of
      adenoid cystic carcinoma (age range of patients, 33 to 74 years). Three
      histologic grades were defined: grade I: completely glandular; grade II: < 30%
      solid areas, and grade III: > or = 30% solid pattern. In 19 of 31 cases,
      immunohistochemical stains for estrogen receptor were available. Twelve of 31
      cases were immunohistochemically stained for Ki-67 antigen using MIB1 antibody.
      Ten of 20 tumors were subareolar. All tumors were grossly circumscribed; however,
      12 of 20 (60%) had focal infiltration peripherally. Five of 19 tumors were
      estrogen receptor positive. There was no statistical correlation between MIB1
      score and histologic grade, nuclear grade, infiltration of the adjacent fat or
      breast parenchyma, or estrogen receptor status. All patients were alive with no
      evidence of disease after a median follow-up of 7 years. Neither histologic or
      nuclear grading nor proliferative activity were useful prognosticators. None of
      the tumors had lymph node metastases. Therefore, axillary lymph node dissection
      may not be necessary. Because more than half of adenoid cystic carcinomas are
      infiltrative focally, the most important therapeutic goal is complete tumor
      removal with uninvolved margins of excision.

PMID- 9591728
TI  - Fibrosarcomatous ("high-grade") dermatofibrosarcoma protuberans:
      clinicopathologic and immunohistochemical study of a series of 41 cases with
      emphasis on prognostic significance.
AB  - The fibrosarcomatous variant of dermatofibrosarcoma protuberans (FS-DFSP)
      represents an uncommon form of DFSP, in which the prognostic influence of the
      fibrosarcomatous component is still debated. We analyzed the clinicopathologic
      and immunohistochemical features in a series of 41 patients. Patient age ranged
      from 8 to 87 years (median, 48 years), and 19 patients were female. Twenty five
      lesions were seen on the trunk, 6 on the upper limbs, and 4 on the lower limbs,
      and five neoplasms were located in the head/neck region; in one case, exact
      anatomic site was unknown. Twenty seven tumors involved purely dermal and
      subcutaneous tissues, in 10 cases, deeper structures were also involved, 1 case
      arose in the breast, and, in 3 cases, it was impossible to define exact depth of
      the lesion. Preoperative duration ranged from 1 month to 60 years (median, 3
      years). Twenty six tumors were excised locally with clear margins, 7 were treated
      by wide excision, 3 by incomplete excision, and, in 4 patients, the lesion was
      shelled out. In one case, exact treatment was unknown. In addition, radiotherapy
      was administered in three cases and chemotherapy in one case. Histologically, the
      lesions showed areas of typical, low-grade DFSP adjacent to fibrosarcomatous
      areas. In four cases, a previously ordinary DFSP recurred as pure fibrosarcoma,
      in two cases, local recurrence of FS-DFSP showed features of ordinary DFSP.
      Fibrosarcomatous change was more common in the primary (de novo) lesions than in
      recurrent lesions (3.6:1). Proportion of fibrosarcoma varied between < 30% in 6
      cases to > 70% of tumor tissue in 21 cases. An abrupt transition between both
      components was seen in 19 cases. The fibrosarcomatous component showed focal
      necrosis in seven cases and showed a higher mitotic rate in comparison with
      ordinary DFSP areas (mean, 13.4 versus 2.3 mitoses in 10 high-power fields).
      Additional histologic features included progression to pleomorphic sarcoma in 2
      recurrent cases, melanin-pigmented cells (Bednar FS-DFSP) in 1 case, focal myxoid
      change in 13 cases, plaque or keloidlike hyalinization in 3 cases, and myoid
      bundles and nodules in 9 cases. Immunohistochemically, tumor cells in DFSP areas
      stained positively for CD34, whereas, in FS-DFSP areas, only 15 out 33 cases were
      positive for CD34. Follow-up in 34 of 41 patients (mean, 90 months; median, 36
      months) revealed local recurrence in 20 patients (58%) (recurrence occurred in 5
      patients on two or more occasions). Metastases (5 lung, 1 bone, and 1 soft
      tissue) were seen in 5 patients (14.7%), and 2 patients have died of tumor to
      date (5.8%). Necrosis, high mitotic rate (> 10 mitoses per 10 high-power fields),
      and presence of pleomorphic areas in FS-DFSP tended to be related with poor
      clinical outcome, but no statistically significant association was detected.
      Fibrosarcomatous change in DFSP represents a form of tumor progression in DFSP
      and is associated with a significantly more aggressive clinical course than in
      ordinary DFSP, indicating a possible need for treatment intensification in such
      cases.

PMID- 9591729
TI  - Extraskeletal osteosarcomas: a clinicopathologic study of 25 cases.
AB  - A follow-up investigation of 25 cases of extraskeletal osteosarcomas diagnosed at
      the Center for Bone and Soft Tissue Tumors, Aarhus University Hospital, Denmark,
      in the period from 1970-1995 was undertaken. The immunohistochemical profile of
      these tumors was evaluated using a panel of 10 antibodies, and the value of
      alkaline phosphatase staining in differential diagnostic situations also was
      considered. The study revealed that this tumor is high-grade malignant and
      affects adults (median age, 67 years; range, 35-82 years) at diagnosis. The thigh
      (52%) was the most common tumor location. Seven tumors were superficial, whereas
      the remaining 18 were intramuscular. Two patients with superficial tumors
      previously received radiation to the area. Local recurrences developed in 9 (36%)
      patients and distant metastases developed in the lungs in 15 (60%) patients as
      the most common site. Median survival time was 24 months, and the cause-specific
      survival rate at 5 years was less than 25%. Thirteen (52%) intramuscularly
      located extraskeletal osteosarcomas were of the fibroblastic subtype, often with
      sparse amounts of osteoid. They could be separated from malignant fibrous
      histiocytoma on the basis of a strongly positive alkaline phosphatase reaction.
      Immunohistochemistry did not reveal characteristic features because positivity
      for vimentin, occasional positivity for desmin, actin, S-100, epithelial membrane
      antigen, cytokeratin, and p-53 may be observed in many other pleomorphic
      sarcomas. Various histopathologic factors, such as tumor size, tumor depth,
      histopathologic subtype, malignancy grade (IIIA versus IIIB), MIB-1, and p53
      reactivity were analyzed in relation to clinical course. Only MIB proliferation
      was correlated to prognosis, with significantly longer survival in patients with
      tumors with MIB-1 values less than 24%. Our study has shown extraskeletal
      osteosarcoma to behave in a highly aggressive fashion. Alkaline phosphatase
      staining compared with immunohistochemistry proved to be superior in the
      differentiation from other pleomorphic sarcomas.

PMID- 9591730
TI  - A103: An anti-melan-a monoclonal antibody for the detection of malignant melanoma
      in paraffin-embedded tissues.
AB  - Melan-A is a previously defined, melanocyte differentiation antigen, and an anti
      Melan-A murine monoclonal antibody, A103, was recently developed by our group. In
      this study, we evaluated A103 immunoreactivity on formalin-fixed, paraffin
      embedded tissues, exploring the potential of A103 in the diagnosis of metastatic
      melanoma. Seventy-five metastatic melanomas, 10 primary melanomas, and 10 benign
      melanocytic nevi were tested. The reactivity of A103 was compared with HMB-4, an
      anti-gp100 antibody. Results showed that all nevi were A103 positive, and most
      primary melanomas were A103 and HMB45 positive. Of 75 metastatic melanomas, 61
      (81%) were A103 positive, and 56 (75%) were HMB45 positive. Of 19 HMB45-negative
      lesions, 8 were A103 positive; of 14 A103-negative lesions, 3 were HMB45
      positive. Eleven metastatic lesions, as well as 2 of 10 primary melanomas, were
      dual negative. These negative cases consisted mainly of the spindle cell and
      desmoplastic variants. Of the positive cases, A103 showed homogeneous staining in
      a significantly higher proportion of cases than HMB45 (72% versus 52%). In
      addition, focal staining with less than 5% reactive tumor cells was seen more
      frequently in HMB45 (12 of 56) than in A103 (5 of 61). These results indicated
      that A103 can be used as a first-line antibody in the diagnosis of metastatic
      melanoma. Our results also showed that A103 reacted with angiomyolipoma, which is
      known to be HMB45 positive. Of normal tissues, unexpected A103 reactivity was
      observed in the adrenal cortex, granulosa and theca cells of the ovary, and
      Leydig cells of the testis. This A103 immunoreactivity in benign and neoplastic
      tissues of nonmelanocytic origin, the basis of which is unclear, could also be of
      potential diagnostic value.

PMID- 9591731
TI  - Oncocytic adrenocortical neoplasms: a report of seven cases and review of the
      literature.
AB  - Oncocytic neoplasms of the adrenal gland are rare. We describe the
      clinicopathologic and immunohistochemical findings of seven oncocytic
      adrenocortical neoplasms, five oncocytomas, and two oncocytic neoplasms of
      uncertain malignant potential. Three tumors were studied using electron
      microscopy. These neoplasms occurred in five women and two men (median age, 55
      years) with no clinical evidence that the neoplasms were functional. The size of
      the neoplasms varied from 5.0 cm to 13.5 cm. Histologically, each neoplasm was
      composed exclusively of oncocytes. The oncocytomas had very low or absent mitotic
      activity and no evidence of necrosis. The two oncocytic neoplasms of uncertain
      malignant potential had increased mitotic activity and necrosis but no evidence
      of invasion or metastases. Nuclear atypia, either focal or generalized, was found
      in all neoplasms. Immunohistochemical studies performed using fixed, paraffin
      embedded sections showed strong reactivity with the mitochondrial antibody mES-13
      in all neoplasms. Four of five oncocytomas and one oncocytic neoplasm of
      uncertain malignant potential expressed keratin, predominantly keratin 18, as
      shown using the CAM 5.2 and AE3 antibodies. Two neuroendocrine-associated
      markers, neuron specific enolase and synaptophysin, were positive in seven and
      five neoplasms, respectively. However, all neoplasms were negative for the other
      neuroendocrine markers tested, including chromogranin A, tyrosine hydroxylase,
      and dopamine beta-hydroxylase, as well as for epithelial membrane antigen, S100,
      and p53. Using the MIB-1 (Ki-67) antibody, proliferative activity was increased
      in both oncocytic neoplasms of uncertain malignant potential. All six patients
      with available clinical follow-up data are alive without evidence disease,
      although the follow-up interval is relatively short (< 2 years) for the two
      patients with oncocytic neoplasms of uncertain malignant potential. We conclude
      that oncocytic adrenocortical neoplasms are nonfunctional tumors that can become
      large before they are detected by radiologic studies. The majority of neoplasms
      are benign and should not be misdiagnosed as carcinoma.

PMID- 9591732
TI  - Immunohistochemical study of testicular sex cord-stromal tumors, including
      staining with anti-inhibin antibody.
AB  - Inhibin is a peptide hormone produced by ovarian granulosa cells and testicular
      Sertoli cells. Ovarian granulosa cell and other sex cord-stromal tumors usually
      exhibit positive immunohistochemical staining with antiinhibin antibodies, and
      this may be valuable in differentiating these neoplasms from histologic mimics.
      In the present study, we investigated the immunohistochemical staining of
      testicular sex cord-stromal tumors using antiinhibin. Immunostaining with CAM5.2,
      vimentin, S-100 protein, desmin, epithelial membrane antigen (EMA),
      carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) also
      was performed because few studies have investigated in detail the immunophenotype
      of testicular sex cord-stromal tumors. Fifteen of 16 Leydig cell tumors exhibited
      strong positive staining with antiinhibin. A proportion of Leydig cell tumors
      also stained positively with CAM5.2 (7 of 16), vimentin (14 of 16), S-100 protein
      (10 of 16), desmin (2 of 16) and epithelial membrane antigen (4 of 16). Four of
      six testicular sex cord-stromal tumors with varying degrees of Sertoli or
      granulosa cell differentiation were positive with antiinhibin, as were two of
      three sex cord-stromal tumors that were unclassified. Some of these tumors were
      positive with CAM 5.2, vimentin, S-100 protein, desmin, and epithelial membrane
      antigen. All tumors were negative with carcinoembryonic antigen and placental
      alkaline phosphatase. The immunohistochemical findings show that, analogous to
      their ovarian counterparts, most testicular sex cord-stromal tumors are
      immunoreactive with antiinhibin. Immunohistochemistry using this antibody as part
      of a panel may be valuable in confirming a diagnosis of testicular sex cord
      stromal tumor and in differentiating these neoplasms from others that may mimic
      them.

PMID- 9591733
TI  - Angiosarcoma of the ovary: clinicopathologic and immunohistochemical analysis of
      four cases with a broad morphologic spectrum.
AB  - Angiosarcoma most frequently occurs in the skin of the head and neck region of
      elderly persons, lymphedematous limbs, or in deep soft tissue but only rarely has
      been described to occur in the female genital tract. Four cases of angiosarcoma
      of the ovary are described herein. They occurred in patients 25 to 42 years old
      (median, 31 years). The most common clinical presentation was abdominal pain. All
      of the tumors were unilateral, hemorrhagic, and ranged from 3.5 cm to 14 cm
      (median, 13 cm). The histologic appearance of the tumors was varied, and often
      the vascular nature of the tumor was not apparent immediately. Some of the tumors
      had a fascicular growth pattern composed of spindle-shaped cells with ovoid
      nuclei and ample eosinophilic cytoplasm closely mimicking leiomyosarcoma. Other
      tumors resembled ovarian yolk sac tumor with a reticular growth pattern, whereas,
      in other areas, cystic structures lined by hobnailed hyperchromatic enlarged
      nuclei simulated clear cell carcinoma of the ovary. Despite these misleading
      morphologic findings, all cases were characterized, at least focally, by
      vasoformative channels or discrete cytoplasmic vacuoles, and all were
      immunoreactive for vascular markers. Two patients with spread of tumor outside of
      the ovary died 1 month and 2 years after initial diagnosis, respectively. Two
      patients with tumor confined to the ovary are alive without evidence of disease 3
      and 14 months after diagnosis, respectively. The differential diagnosis of this
      unusual neoplasm is discussed, and the literature is reviewed.

PMID- 9591734
TI  - Malignant adenomyoepithelioma of the breast with mixed osteogenic, spindle cell,
      and carcinomatous differentiation.
AB  - A 50-year-old woman had a malignant tumor of the left breast, which recurred
      twice, metastasized, and caused death after 39 months. Histologically, the
      original neoplasm and the first recurrence comprised an adenomyoepithelioma, in
      addition to a sarcoma composed of trabeculae of mature and immature bone,
      osteoid, and partly calcified, dense collagenous tissue. The trabeculae were
      lined by alpha-smooth muscle actin-positive mononuclear tumor cells, which also
      extended into the stroma. Similarly, scattered osteoclastlike, multinucleate
      giant cells were present in the stroma and in the region of the trabeculae. This
      same pattern of adenomyoepithelioma and osteosarcoma also was seen in the last
      recurrence, together with a proliferation of undifferentiated malignant spindle
      shaped cells. The last biopsy also contained a separate small focus of invasive
      ductal carcinoma of usual type. It was concluded that this, apparently unique,
      tumor probably represented an adenomyoepithelioma in which a metaplastic sarcoma
      of osteogenic and undifferentiated types developed from the myoepithelial
      element, and in which a carcinoma developed from the epithelial component.

PMID- 9591735
TI  - Primary T-cell-rich B-cell lymphoma of the Waldeyer's ring: a pathologic
      condition more frequent than presupposed?

PMID- 9591736
TI  - Variations in insulin sensitivity in spontaneously hypertensive rats from
      different sources.
AB  - We investigated the possibility of variations in the genetic transmission of
      insulin sensitivity in the offspring of spontaneously hypertensive rats (SHRs)
      and Wistar Kyoto rats (WKYs) obtained from different sources (Charles River,
      Tokyo, Japan [NCrj]; and Funabashi Farm, Chiba, Japan [Izm]) with the insulin
      suppression test (IST) using a somatostatin analog, glucose, and insulin. The
      steady-state blood glucose (SSBG) in the IST and the glucose infusion required
      (GIR) in the euglycemic-hyperinsulinemic clamp differ significantly between obese
      and lean Zucker rats, indicating that both methods are useful for identifying
      insulin resistance. The fasting blood glucose and SSBG of the IST were
      significantly higher in SHR/Izm than in WKY/Izm. We did not observe a significant
      difference between SHR/NCrj and WKY/NCrj. These results indicate that the genetic
      transmission of hypertension and impaired insulin sensitivity may be variable and
      that insulin resistance does not play an important role in the pathogenesis of
      hypertension in the SHR.

PMID- 9591737
TI  - Hyperglucagonemia and the immediate fate of dietary leucine: a kinetic study in
      humans.
AB  - The possible role of glucagon in determining the fate of dietary absorbed amino
      acids within the splanchnic bed was investigated in five healthy male volunteers.
      A kinetic study was performed involving a continuous 240-minute infusion of L
      [5,5,5-2H3]leucine and D-[6,6-2H2]glucose by vein, while L-[1-13C]leucine was
      infused by a feeding tube into the duodenum (intragut [i.g.]) along with a
      constant intravenous (i.v.) infusion of somatotropin release-inhibitory factor
      (SRIF) combined with insulin, growth hormone, and glucagon. In random order,
      glucagon was infused at a rate of 0.4 ng x kg(-1) x min(-1) in one experiment and
      1.2 ng x kg(-1) x min(-1) in the other experiment, while insulin and growth
      hormone were kept at constant serum levels, respectively, 37+/-13 pmol x L(-1)
      and 5+/-0.2 microg x L(-1). The diet was provided as an L-amino acid solution
      including 60 micromol x kg(-1) x h(-1) leucine without fat and carbohydrate.
      During the higher rate of glucagon infusion, there was an increase in plasma
      glucagon and glucose concentrations, glucose flux, and net dietary leucine
      release into the periphery from the splanchnic bed. Splanchnic removal and uptake
      of leucine were decreased with increased glucagon infusion. There were no
      statistical differences in the plasma leucine level and i.v. and i.g. leucine
      fluxes at the two glucagon levels, although leucine metabolic clearance increased
      (0.74 v 0.85 L x kg(-1) x h(-1), P=.08) in the case of glucagon excess. Plasma
      glucose increased with glucagon excess and was negatively correlated (P < .05)
      with the plasma leucine level (r=-.348) and i.v. (r=-.459) or i.g. (r=-.359)
      leucine fluxes. The negative correlation between plasma glucagon and leucine
      levels was also significant (r=-.684). No significant correlation was found
      between dietary leucine splanchnic removal and glucose, glucagon, or leucine
      plasma concentrations. We conclude that glucagon in excess has only a small
      quantitative effect on the overall handling of dietary leucine, and hypothesize
      that more leucine is exported to the peripheral tissues under these hormonal
      conditions.

PMID- 9591739
TI  - A study of insulin resistance using the minimal model in nondiabetic familial
      combined hyperlipidemic patients.
AB  - The presence of insulin resistance in 20 male nondiabetic patients with familial
      combined hyperlipidemia (FCH) and 20 controls of similar age and body mass index
      (BMI) was investigated using the minimal model method modified by the
      administration of insulin and an oral glucose tolerance test. The peripheral
      sensitivity of insulin, expressed as the insulin sensitivity index (Si), was
      1.91+/-1.05 and 2.86+/-1.19 x 10(-4) x min(-1) x mU/L in FCH patients and
      controls, respectively (P < .01), and the corresponding value for the peripheral
      utilization of glucose independently of insulin (Sg) was 1.70+/-1.13 in FCH
      patients and 2.35+/-0.60 x 10(-2) x min(-1) in controls (P < .02). In the FCH
      group, the Si value correlated significantly (P < .05) with the waist to hip
      ratio (WHR), plasma triglycerides (TG), free fatty acids (FFA), and the area
      under the curve of glucose (AUCg) and insulin (AUCi). In the control group, the
      correlation also reached statistical significance (P < .05) with age, BMI, WHR,
      blood pressure, TG, AUCg, and AUCi. Subgrouping the subjects with respect to
      central obesity defined as a WHR of 0.95 or greater, we observed lower Si values
      in obese and non-obese FCH subjects relative to controls (P < .02). The mean Si
      value in obese subjects was significantly lower than in non-obese FCH subgroups
      (1.40+/-0.79 v 2.68+/-0.95 x 10(-4) x min(-1) x mU/L, respectively, P < .01). In
      conclusion, a higher degree of insulin resistance relative to control values
      appears to be an integral part of the metabolic derangements observed in FCH, and
      central-trunk obesity exacerbates the insulin resistance syndrome.

PMID- 9591738
TI  - Increased capillary filtration of albumin in diabetic patients--relation with
      gender, hypertension, microangiopathy, and neuropathy.
AB  - The aim of this study was to investigate the factors associated with an increase
      in capillary filtration of albumin (CFA) in a large series of diabetic patients
      and its relationship with gender, hypertension, microangiopathy, and neuropathy.
      One hundred sixty-three unselected diabetic patients, 74 type I and 89 type II,
      were included. An isotopic test of CFA was performed with 99m technetium-labeled
      albumin injected intravenously. Radioactivity was counted externally at the
      forearm with a gamma camera before, during, and after venous compression. After
      removal of venous compression, interstitial albumin retention (AR) was calculated
      and the radioactivity disappearance curve was analyzed by the Fast Fourier
      transform, which provides an index for lymphatic uptake of interstitial albumin
      (low-frequency to high-frequency amplitude peak ratio [LF/HF]). An increase in AR
      and LF/HF was found in 65 (39.9%) and 117 (71.7%) patients, respectively.
      Increased AR was significantly more frequent in women than in men (P=.018) and in
      patients without microangiopathic complications than in those with them (P=.028).
      In men, it was significantly more frequent in type I versus type II diabetic
      patients (P=.004), and AR was significantly higher in patients with peripheral
      neuropathy than in those without (P=.004). The LF/HF was also significantly
      higher in men with peripheral neuropathy (P=.045). In women, the AR level
      correlated negatively with postprandial glycemia (P=.006) and was significantly
      higher in patients without microangiopathic complications (P=.003). These data
      suggest the role of hormonal factors, both sex steroids and insulin, and the
      major role of peripheral neuropathy in the increase in CFA. The highly prevalent
      increase in CFA before the onset of microangiopathic complications is consistent
      with the presence of a functional microcirculatory disorder that might contribute
      to the occurrence of microangiopathic lesions.

PMID- 9591740
TI  - The conjoint trait of low high-density lipoprotein cholesterol and high
      triglycerides in adolescent black and white males.
AB  - To evaluate the interrelationships among body composition, blood pressure, and
      lipid phenotypes in adolescent black and white boys, we assessed racial
      distributions of lipids, blood pressure, and obesity and their joint occurrence
      in black and white boys aged 10 to 15 years. Subjects were recruited from
      Cincinnati (OH) schools. Because the differences in high-density lipoprotein
      cholesterol (HDL-C) and triglycerides (TGs) are the most profound coronary heart
      disease (CHD) risk factor differences between black and white males, we assigned
      subjects to one of four low-HDL-C and high-TG categories (normal and increased
      risk) using the age/race-specific 25th (HDL-C) and 75th (TG) percentiles. We then
      assessed racial distributions of lipids, blood pressure, and obesity by these
      phenotypes. Age differences between the black and white participants were
      significant, with the former about 3 months younger (P=.03), but black boys were
      more mature and were significantly taller and heavier and had a greater body mass
      index ([BMI] weight in kilograms divided by height in centimeters squared).
      Differences in the sum of the triceps, subscapular, and suprailiac skinfolds were
      not significant. Blacks had significantly higher HDL-C, lower TG, and higher
      diastolic blood pressure (DBP), but differences in systolic blood pressure (SBP)
      were not significant. In both racial groups, the body composition measures were
      significantly correlated with HDL-C, TG, and blood pressure levels; the
      correlations between HDL-C and both weight and BMI were significantly stronger in
      white boys. The proportion of boys of each race with low HDL-C and high TG was
      similar by design. In both racial groups, subjects with the conjoint trait had a
      significantly greater BMI, triceps skinfold, and sum of skinfolds than subjects
      in the other phenotypic groups. For white boys, participants with the conjoint
      trait had the highest SBP and DBP; differences in SBP were significant for
      comparisons to the normal- and high-TG group alone, and differences in DBP were
      significant for the comparison between normal and low HDL-C alone. For black
      boys, subjects with both normal HDL-C and TG had significantly lower SBP than
      boys with either the conjoint trait or high TG alone; none of the group
      differences in DBP were significant. Black had significantly less dense LDL (more
      LDL-C per apolipoprotein [apo] B). In each racial group, boys with the conjoint
      trait had the most dense LDL, significantly more dense than in any of the other
      phenotypes in black boys and significantly more dense than in boys with low HDL-C
      alone and normal boys in the white group. In both racial groups, the occurrence
      of no risk factors (>75th percentile TG, BMI, SBP, and DBP or <25th percentile
      HDL-C) and three or more risk factors was greater than expected by chance alone,
      and the occurrence of exactly one risk factor and two factors was less. When
      examined by phenotypic groups within race, boys in each racial group with the
      normal phenotype had a greater than expected percentage with no risk factors, and
      white boys with the conjoint trait were more likely to have a marked increase in
      multiple risk factors. Possible mechanisms for this clustering of risk factors
      and for the racial differences in the patterns are discussed.

PMID- 9591741
TI  - Impact of family history of diabetes on the assessment of beta-cell function.
AB  - Numerous factors impinge on beta-cell function, and include the genetic
      background and insulin sensitivity of the individual. The aim of the present
      study was to evaluate the impact of a family history of non-insulin-dependent
      diabetes mellitus (NIDDM) on beta-cell function and to determine whether the
      relationships between beta-cell function and insulin sensitivity and age are
      influenced by a family history of diabetes. Thirty-three healthy control subjects
      (CON), 20 normal glucose-tolerant first-degree relatives of known NIDDM patients
      (REL), and 12 nondiabetic identical twins with an identical twin with known NIDDM
      were studied. Insulin and C-peptide responses to an acute intravenous glucose
      (AIRg) and glucagon bolus (at euglycemia [AIR[G.GON]]) were measured, as well as
      each individual's insulin sensitivity. Fasting insulin and C-peptide levels were
      similar in all groups. AIRg was significantly reduced by 65% in the nondiabetic
      twins compared with the CON and REL groups, with the latter group being similar
      to CON, whereas for the AIR[G.GON], the insulin responses in the twin subjects
      were reduced only by 35% compared with CON. Following stepwise (default) multiple
      regression analysis, three independent variables (insulin sensitivity, 23%;
      family history of NIDDM, 20%; and fasting glucose, 7%) were identified, and these
      combined to fit a model for prediction of acute beta-cell responses to glucose
      that yielded an R2 (adjusted) value of 50%. Following analysis of covariance
      (ANCOVA), a positive family history of NIDDM and insulin sensitivity but not the
      age of the subject were confirmed as separate factors affecting AIRg. In
      conclusion, in subjects with normal or mild glucose intolerance, the individual's
      genetic background and insulin sensitivity are important determinants of insulin
      secretion.

PMID- 9591742
TI  - A high-stearic acid diet does not impair glucose tolerance and insulin
      sensitivity in healthy women.
AB  - Results in epidemiological and experimental studies suggest that a diet rich in
      saturated fat may affect insulin sensitivity. However, no published data are
      available on the effect of stearic acid in this respect. Therefore, we examined
      the effects of a high-stearic acid diet and a high-oleic acid diet on glucose
      metabolism, serum lipids and lipoproteins, and blood coagulation factors in 15
      healthy female subjects. Subjects followed the two experimental diets for 4 weeks
      according to a randomized crossover design. Both experimental diet periods were
      preceded by consumption of a baseline diet for 2 weeks. The diets provided 36% of
      energy (E%) as fat. In the experimental diets, 5 E% stearic or oleic acid was
      substituted for 5 E% of saturated fatty acids in the baseline diet. After the
      experimental diets, no differences were found in the insulin sensitivity index
      (mean+/-SEM, 5.4+/-1.9 v 5.2+/-1.6 x 10(-4) min(-1) x microU(-1) x mL(-1),
      nonsignificant [NS]), glucose effectiveness (0.026+/-0.006 v 0.026+/-0.003 min(
      1), NS), or first-phase insulin reaction ([FPIR] 368+/-57 v 374+/-66 mU/L x min,
      NS). The concentration of serum lipids and lipoproteins and blood coagulation
      factors did not differ after the diet periods. In conclusion, a diet rich in
      stearic acid did not deteriorate glucose tolerance or insulin action in young
      healthy female subjects as compared with a diet rich in oleic acid.

PMID- 9591743
TI  - Relationships between fasting plasma insulin, anthropometrics, and metabolic
      parameters in a very old healthy population. Associazione Medica Sabin.
AB  - Several studies have shown that insulin resistance and hyperinsulinemia are
      associated with many metabolic disorders predisposing to coronary heart disease
      (CHD). This syndrome has been termed syndrome X. However, it is not completely
      known whether these relationships are still present in the elderly, or whether
      other factors such as age, gender, and body fat distribution modulate them.
      Therefore, we investigated the relationship between fasting plasma insulin, total
      and regional adiposity, fasting plasma glucose and lipids, plasma plasminogen
      activator inhibitor-1 (PAI-1), fibrinogen, and coagulation factor VII in a sample
      of 100 healthy free-living octogenarians-nonagenarians (52 men and 48 women) who
      were disability-free according to the Katz index. By univariate analysis, fasting
      insulin correlated positively with all anthropometric measures except the waist
      to hip ratio (WHR) in women. There was a positive correlation between fasting
      insulin and fasting glucose (r=.40, P < .01), plasma triglycerides ([TGs] r=.21,
      P < .05), and PAI-1 levels (r=.33, P < .01), whereas a negative relation was
      found with high-density lipoprotein cholesterol (HDL-C) and apolipoprotein, A-I
      (apo A-I) levels (r=-.22 and =-.24, respectively, P < .05). These relationships
      were weaker and less significant in women. In pooled data, stepwise multiple
      regression analysis showed an independent relationship of both the body mass
      index (BMI) and fasting insulin level with TGs (R2=.14), while gender and fasting
      insulin were the best predictors of HDL-C variance (R2=.17). Furthermore, fasting
      insulin was the only variable independently related to PAI-1 (R2=.12). Our
      findings support the existence of a metabolic syndrome even in very old age by
      showing that high insulin levels are related to various metabolic and hemostatic
      disorders.

PMID- 9591744
TI  - Bone mineral density in prepubertal children with beta-thalassemia: correlation
      with growth and hormonal data.
AB  - Patients with beta-thalassemia major (beta-thalassemia) frequently have bone
      disorders of multifactorial etiology. We attempted to analyze the relationship
      between the bone mineral density ([BMD] measured by dual-photon absorptiometry)
      and auxanologic parameters, degree of siderosis, function of the growth hormone
      (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein-3 (IGFBP3) axis,
      calcium-phosphate balance, parathyroid hormone (PTH), and cytokines (interleukin
      1beta [IL-1] and tumor necrosis factor-alpha [TNF-alpha]) in 30 prepubertal
      children with beta-thalassemia major and 15 age-matched children with
      constitutional short stature (CSS), who have normal glucose tolerance and thyroid
      function. Children with beta-thalassemia had a significantly decreased BMD and
      mean BMD% for age and sex (0.75+/-0.24 g/cm2 and 71%+/-10%, respectively) versus
      children with CSS (1.06+/-0.3 g/cm2 and 92%+/-7%, respectively). Thalassemic
      patients had significantly lower circulating concentrations of IGF-I and IGFBP3
      (49+/-21 ng/mL and 1.2+/-0.25 mg/L, respectively) compared with control children
      (153+/-42 ng/mL and 2.1+/-0.37 mg/L, respectively). The GH response to
      provocation by clonidine and glucagon was defective (peak GH < 7 microg/L) in 12
      of the 30 thalassemic children. Serum concentrations of IL-1beta and TNF-alpha
      did not differ among the two study groups. Hypocalcemia was detected in five of
      the 30 thalassemic patients: hypoparathyroidism was diagnosed in two of the five
      and rickets in the other three. BMD was highly correlated with the circulating
      concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters
      (age, weight, height, height standard deviation score [HSDS], and body mass index
      [BMI]). It is suggested that increasing the circulating IGF-I concentration
      through aggressive nutritional therapy and/or GH/IGF-I therapy with
      supplementation with vitamin D and/or calcium might improve bone growth and
      mineralization and prevent the development of osteoporosis and consequent
      fractures in these patients. Such therapy requires blinded controlled trials.

PMID- 9591745
TI  - Role of glucose and glutamine synthesis in the differential recovery of 13CO2
      from infused [2-13C] versus [1-13C] acetate.
AB  - Carbon exchange in the Krebs cycle may result in underestimation of substrate
      oxidation measured with 13C-labeled substrates, since carbon labeled in position
      2 of acetyl-coenzyme A (CoA) could be incorporated into glucose (via
      gluconeogenesis) and glutamine. Five healthy volunteers were therefore infused
      with [1-13C] and [2-13C] acetate at a rate of 0.5 micromol x kg(-1) x min(-1) for
      165 minutes on two different occasions in randomized order. Whole body acetate
      turnover did not differ between the two tracers: 7.9+/-0.3 and 7.5+/-0.6 micromol
      x kg(-1) x min(-1) (nonsignificant [NS]) for [1-13C] and [2-13C] acetate,
      respectively. Isotopic 13C enrichment was higher in expired CO2 (0.177+/-0.021 v
      0.089+/-0.009 atom percent excess [APE], P < .01) and lower in glucose (0.074+/
      0.017 v0.291+/-0.061 mole percent excess [MPE], P < .01) for [1-13C] acetate
      compared with [2-13C] acetate, respectively, at the end of the infusions.
      Glutamine isotopic enrichment was slightly but not significantly higher when
      infusing [1-13C] acetate versus [2-13C] acetate (0.348+/-0.038 v0.495+/-0.069
      MPE, NS, respectively). At the end of the experiment, the recovery of 13CO2 from
      [1-13C] acetate was 44.8%+/-2.7%, and from [2-13C] acetate, 22.6%+/-1.3%. A
      significant correlation was observed between the differences in 13C enrichment of
      CO2 for the two tracers and glucose (deltaCO2=0.424 x deltaglucose + 0.001,
      R2=.9856, P=.0007) or glutamine (deltaCO2=0.621 x deltaglutamine + 0.004,
      R2=.9573, P=.0038) during the infusion. These results suggest that (1) although
      gluconeogenesis appears to be more responsible than glutamine for the
      differential recovery of [2-13C] versus [1-13C] acetate, other secondary pathways
      are probably also implicated; and (2) different recovery correction factors
      should be applied when measuring substrate oxidation with a stable isotope tracer
      depending on the expected position of 13C in acetyl-CoA.

PMID- 9591746
TI  - Insulin regulates lipoprotein lipase activity in rat adipose cells via wortmannin
      and rapamycin-sensitive pathways.
AB  - Lipoprotein lipase (LPL) hydrolyzes the triacylglycerol component of circulating
      lipoprotein particles, mediating the uptake of fatty acids into adipose tissue
      and muscle. Insulin is the principal factor responsible for regulating LPL
      activity in adipose tissue, yet the mechanisms whereby insulin controls LPL
      expression are unknown. The current studies used wortmannin, a specific inhibitor
      of phosphatidylinositol (PI) 3-kinase, and rapamycin, a specific inhibitor of
      activation of phosphoprotein 70 ribosomal protein S6 kinase (p70s6k), to explore
      some of the components of the insulin signaling pathway controlling LPL activity
      in adipose cells. Preincubation of isolated rat adipose cells with wortmannin
      completely abrogated the stimulation of LPL activity by insulin, while
      preincubation with rapamycin caused approximately a 60% inhibition of insulin
      stimulated LPL activity. Thus, the current studies show that the regulation of
      adipose tissue LPL by insulin is mediated via a wortmannin-sensitive pathway,
      most likely PI 3-kinase, and that a rapamycin-sensitive pathway, most likely
      p705s6k, constitutes an important downstream component in the insulin signaling
      pathway through which LPL is regulated.

PMID- 9591747
TI  - Lack of interaction of apolipoprotein E phenotype with the lipoprotein response
      to lovastatin or gemfibrozil in patients with primary hypercholesterolemia.
AB  - The magnitude of serum lipid changes in response to hypolipidemic drugs varies
      considerably between individuals. These differences may be due to interactions
      between genetic and environmental factors that effect drug bioavailability or the
      capacity of the lipid-regulating enzyme and receptor targets to be affected. The
      apolipoprotein E (apoE) gene locus has been examined in this regard, but reports
      are conflicting on the effect of its variability on the response to hypolipidemic
      drugs. We investigated the effect of apoE polymorphism on the serum lipid
      response to the hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase
      inhibitor lovastatin and the fibric acid derivative gemfibrozil. Lipoprotein
      changes were assessed after 12 weeks of therapy in 106 patients with primary
      hypercholesterolemia and combined hyperlipidemia treated with lovastastin and in
      63 given gemfibrozil therapy. No significant effect of the apoE phenotypes E3/2,
      E3/3, or E4/3 on the heterogeneity of lipid responses to either drug was found.

PMID- 9591748
TI  - Effect of linoleic acid on endothelial cell inflammatory mediators.
AB  - Selected lipids may influence the inflammatory cascade within the vascular
      endothelium. To test this hypothesis, endothelial cells were treated with
      linoleic acid (18:2, n - 6) for 12 hours and/or tumor necrosis factor-alpha (TNF)
      for 4 hours. For a combined exposure to 18:2 and TNF (18:2 + TNF), cells were
      first preenriched with 18:2 for 8 hours before exposure to TNF for an additional
      4 hours. Exposure to 18:2 increased cellular oxidative stress, activated nuclear
      factor-kappaB (NF-kappaB), increased interleukin-8 (IL-8) production, and
      elevated intercellular adhesion molecule-1 (ICAM-1) levels. A combined exposure
      to 18:2+ TNF resulted in decreased NF-kappaB activation compared with TNF
      treatment alone. In addition, preexposure to 18:2 altered TNF-mediated IkappaB
      alpha signaling. Within the first 15 minutes of a 90-minute period, cytoplasmic
      levels of IkappaB-alpha decreased more rapidly in cells treated with 18:2 + TNF
      compared with TNF, suggesting translocation and activation of NF-kappaB in
      cultures that were pretreated with 18:2 before TNF exposure. A combined exposure
      to 18:2+TNF had various effects on IL-8 production and ICAM-1 levels depending on
      the time of exposure. For example, 18:2 + TNF treatment increased ICAM-1 levels
      at 12 hours but decreased ICAM-1 levels at 24 hours compared with treatment with
      TNF alone. These data suggest that selected fatty acids such as 18:2 can exert
      proinflammatory effects and, in addition, may markedly alter TNF-mediated
      inflammatory events.

PMID- 9591749
TI  - Glucosamine infusion in rats mimics the beta-cell dysfunction of non-insulin
      dependent diabetes mellitus.
AB  - Sustained hyperglycemia can cause peripheral insulin resistance and pancreatic
      beta-cell dysfunction and has been termed glucose toxicity or glucose-induced
      desensitization. Glucosamine, a product of glucose flux through the hexosamine
      biosynthetic pathway (HBP), causes insulin resistance in peripheral tissues and
      has been shown to cause abnormal glucose-insulin secretion coupling, and thus has
      been implicated in the pathogenesis of glucose toxicity. Here, we investigate
      whether glucosamine-induced insulin secretory dysfunction is specific to glucose
      or also extends to nonglucose secretagogues such as arginine. Two groups of 12
      weight-matched Sprague-Dawley rats underwent hyperglycemic clamp studies (steady
      state blood glucose, approximately 220 mg x dL(-1)) during infusion of normal
      saline or glucosamine 3.5 mg x kg(-1) x min(-1) over a 100-minute period. Insulin
      levels were measured at baseline and between 90 and 100 minutes. One hundred
      minutes into the hyperglycemic clamp, subgroups of seven rats each (saline- and
      glucosamine-infused rats) received a bolus of arginine (100 mg x kg(-1)) while
      the glucose infusion rate was unaltered. Glucose and insulin levels were measured
      at 1, 3, 5, 10, 15, and 30 minutes after the arginine bolus. Both groups had
      similar fasting glucose and insulin levels. At steady state (60 to 100 minutes),
      glucose levels were almost identical in both groups (223.58+/-3.94 v 224.58+/
      4.34 mg x dL(-1)), but the glucose infusion rate (26.55+/-1.60 v 8.83+/-1.35 mg x
      kg(-1) x min(-1), P < .0001) and insulin level (41.36+/-6.47 v 18.04+/-2.95 mU x
      mL(-1), P < .0001) were markedly reduced in animals receiving glucosamine. Peak
      insulin levels 1 minute after the arginine bolus were lower in rats infused with
      glucosamine versus saline (274.00+/-30.38 v 176.25+/-20.12 microU x ml(-1),
      P=.0319). Total insulin secretion in response to arginine was significantly lower
      in the glucosamine group as determined by the area under the curve (1,268.09+/
      142.27 v 706.77+/-84.79 microU x mL(-1) x min, P=.0054). In conclusion,
      glucosamine causes severe impairment in glucose-induced insulin secretion.
      Further, glucosamine-induced beta-cell secretory dysfunction extends to
      nonglycemic stimuli like arginine. This pattern of insulin secretory dysfunction
      is similar to that observed in patients with non-insulin-dependent diabetes
      mellitus (NIDDM). These data suggest that glucosamine may participate in the
      pathogenesis of glucose toxicity at the level of the beta cell in NIDDM patients.

PMID- 9591750
TI  - Dietary xylitol supplementation prevents osteoporotic changes in streptozotocin
      diabetic rats.
AB  - The effects of 10% and 20% dietary xylitol supplementation on the biomechanical
      properties, trabeculation, and mineral content of long bones were studied in
      streptozotocin-diabetic rats. Forty 3-month-old male Wistar rats were divided
      randomly into four groups of 10. Rats in three groups were administered a single
      injection of streptozotocin (50 mg/kg body weight) to induce type I diabetes,
      while animals in the fourth group were given a sham injection of physiological
      saline. The sham-injected group and one of the streptozotocin-diabetic groups
      were fed the basal diet, while the two diabetic groups were fed the same diet
      supplemented with 10% and 20% xylitol (wt/wt). After 3 months, the rats were
      killed and the long bones were prepared for analysis. The 10% and 20% dietary
      xylitol supplementation significantly prevented the type I diabetes-induced
      decrease in the mechanical stress resistance of the tibia in the three-point
      bending test, the shear stress of the femur in the torsion test, and the stress
      resistance of the femoral neck in the loading test. No statistically significant
      differences were found between any groups in the values for strain or Young's
      modulus in the three-point bending test, or in the values for the shear modulus
      of elasticity in the torsion test. These findings indicate that dietary xylitol
      protects against the weakening of the bone strength properties of both cortical
      and trabecular bone without affecting the elastic-plastic properties.
      Supplementation with 10% and 20% dietary xylitol significantly prevented the type
      I diabetes-induced decrease of humeral ash weight and tibial density.
      Histomorphometric data for the secondary spongiosa of the proximal tibia showed
      that 10% and 20% dietary xylitol supplementation also significantly prevented the
      type I diabetes-induced loss of trabecular bone volume. In conclusion, dietary
      xylitol supplementation protects against the weakening of bone biomechanical
      properties in streptozotocin-diabetic rats. This is related to the preserved bone
      mineral content and preserved trabecular bone volume.

PMID- 9591751
TI  - Plasma leptin in diabetic and insulin-treated diabetic and normal rats.
AB  - Adipose tissue leptin mRNA levels are decreased by food deprivation or induction
      of insulin-deficient diabetes. To determine whether plasma leptin concentrations
      are similarly affected, whether treatment of diabetes with insulin restores
      plasma leptin, and whether this requires restoration of body weight (lost as a
      result of diabetes) and/or normalization of glycemia, we measured plasma leptin
      concentrations in control, untreated streptozotocin (STZ)-diabetic, and insulin
      treated STZ-diabetic rats. Plasma leptin was markedly reduced in untreated STZ
      diabetic rats. Insulin treatment for 4 to 17 days increased plasma leptin
      approximately twofold above control levels. However, despite the hyperleptinemia,
      insulin-treated diabetic rats gained weight at a rate equal to that of sham
      treated controls. Epididymal adipose tissue leptin mRNA levels in 17-day insulin
      treated diabetic rats were equal to but did not exceed sham-control levels,
      unlike plasma leptin. Plasma glucose concentrations in insulin-treated STZ
      diabetic rats were lower than in sham controls. Therefore, to determine whether
      hypoglycemia may be important in increasing plasma leptin, we measured plasma
      leptin levels in diabetic rats infused with insulin for 3 hours along with a
      variable-rate glucose infusion targeting glycemia to 200 or 40 mg/100 mL. Plasma
      leptin rapidly increased in these rats irrespective of target glycemia. Plasma
      leptin also increased rapidly in normal rats infused with insulin and glucose
      (target glycemia, 200 mg/100 mL). We conclude that plasma leptin concentrations
      are markedly reduced under conditions of insulin deficiency and rapidly increased
      by insulin treatment. The increase in plasma leptin does not require restoration
      of body weight and, under glucose clamp conditions, does not depend on target
      glycemia. Hyperleptinemia in insulin-treated diabetic rats is not explained on
      the basis of steady-state leptin mRNA levels, at least as reflected in epididymal
      fat.

PMID- 9591752
TI  - Changes in blood pressure and in vasoactive and volume regulatory hormones during
      semistarvation in obese subjects.
AB  - The mechanisms underlying the reduction in blood pressure that occurs with a
      severe energy-restricted diet were evaluated in 12 obese subjects during 8 days
      on a very-low-calorie diet (1.67 MJ/d) with a constant intake of 17 mmol sodium
      per day. The relationship between changes in blood pressure, sodium balance,
      plasma volume, renin-aldosterone and sympathetic nervous system activities,
      plasma C-terminus and N-terminus of the atrial natriuretic factor (ANF)
      prohormone, brain natriuretic peptide (BNP), and endothelin-1 (ET-1)
      concentrations was investigated. A negative sodium balance was present throughout
      the diet and was associated with a moderate reduction in plasma volume, a marked
      activation of the renin-aldosterone system, and a concomitant reduction in C- and
      N-terminal ANF prohormone levels. Moreover, the postural changes in N-terminal
      proANF and ANF secretion documented before the diet, disappeared after 8 days of
      dieting, in contrast to a greater postural stimulation of aldosterone and renin.
      A negative correlation was found between the changes of C- and N-terminal ANF
      prohormone levels and those of aldosterone. Urinary catecholamine excretion, BNP,
      and ET-1 remained unchanged. These results indicate that the decrease in blood
      pressure occurring during severe caloric restriction was essentially due to the
      reduction in the effective blood volume, as reflected by the stimulation of the
      renin-aldosterone system and the decrease in ANF levels. The lack of any changes
      in catecholamine excretion and endothelin levels suggests that peripheral
      vascular resistance did not change significantly in these circumstances.

PMID- 9591753
TI  - Serum paraoxonase activity and its relationship to diabetic complications in
      patients with non-insulin-dependent diabetes mellitus.
AB  - Paraoxonase (PON) is an esterase associated with high-density lipoprotein (HDL).
      Serum PON activity is affected by PON gene polymorphism (L/M, Leu-Met54, and Q/R,
      Gln-Arg191). We investigated PON activity and polymorphism in 108 patients (53
      men and 55 women) with non-insulin-dependent diabetes mellitus (NIDDM) and 161
      control subjects (82 men and 79 women) matched to the patients by age and gender.
      Serum PON activity was determined using paraoxon as a substrate. PON gene
      polymorphisms were detected by the restriction fragment length polymorphism
      method after a polymerase chain reaction. The mean PON activity in the patients
      was significantly lower than in the controls (116+/-55 and 162+/-57 U/L,
      respectively, P < .001). The distribution of each genotype showed no difference
      between the patient and control groups, and PON activity increased in the order
      of the QQ < OR < RR genotype and MM < LM < LL genotype in both groups. However,
      among each genotype subgroup, the activity was lower in patients than in
      controls. Forty-one patients with retinopathy had lower PON activity than those
      without the complication (94+/-36 and 129+/-61 U/L, respectively, P < .002).
      There was also a significant difference in PON activity between patients with and
      without overt proteinuria (93+/-38 and 122+/-58 U/L, respectively, P < .05).
      Logistic analysis showed that serum PON activity was one of the significant
      factors for retinopathy. These results suggest that decreased PON activity in
      patients with NIDDM is involved in diabetic vascular complications.

PMID- 9591754
TI  - Increase in plasma leptin and Lep mRNA concentrations by food intake is dependent
      on insulin.
AB  - Obese (Lep) gene expression and leptin secretion are regulated by changes in food
      intake. However, the mechanism by which leptin concentrations are altered by
      fasting and feeding is unclear. Since these changes occur in parallel with
      changes in plasma insulin, it is possible that the changes observed are mediated
      by insulin. To test this hypothesis, we studied the role of insulin in the
      regulation of Lep gene expression in epididymal fat and leptin secretion during
      feeding. As shown previously, fasted animals showed significant reductions in Lep
      mRNA, plasma leptin, and plasma insulin concentrations. Conversely, feeding
      increased plasma insulin, Lep mRNA, and plasma leptin. In streptozotocin (STZ)
      treated animals, plasma insulin concentrations were low. This was associated with
      low Lep mRNA and plasma leptin concentrations. Changes in food intake, whether
      fasting or feeding, did not significantly alter plasma insulin levels in STZ
      treated animals. Under these circumstances, Lep mRNA and plasma leptin
      concentrations also remained low. Our results demonstrate that the decrease in
      Lep mRNA and plasma leptin during fasting and the increase with feeding are
      dependent on changes in the plasma insulin concentration.

PMID- 9591755
TI  - Stimulation of rat hepatic amino acid transport by burn injury.
AB  - Burn injury accelerates hepatic amino acid metabolism, but the role of
      transmembrane substrate delivery in this response has not been investigated. We
      therefore studied the effects of cutaneous scald injury on the Na+-dependent
      transport of glutamine and alanine in isolated rat liver plasma membrane
      vesicles. Scald injury resulted in liver damage and a 1.4- to 2.3-fold and 1.5-
      to 2.8-fold stimulation of hepatic transport rates for glutamine and alanine,
      respectively, proportional to the total burned surface area (TBSA) after 24
      hours. Enhanced uptake of glutamine and alanine was attributable to increases in
      the maximum velocity (Vmax) of system N and system A activities, respectively.
      Hepatic amino acid transport activity remained elevated in vesicles from burned
      animals after 72 hours, but the degree of stimulation (1.3- to 1.7-fold for
      glutamine and 1.3- to 1.6-fold for alanine) was less than that observed 24 hours
      after thermal injury. Liver function tests returned to control values after 72
      hours as well, indicating rectification of hepatic damage. In contrast to the
      induction of hepatic system A and system N activity in catabolic states such as
      cancer and endotoxemia, further studies showed that tumor necrosis factor (TNF)
      failed to play a significant role in burn-stimulated amino acid transport rates.
      When combined with plasma liver enzyme profiles, early transient hepatic amino
      acid transporter stimulation may support amino acid-dependent pathways involved
      in the repair of burn-dependent hepatic damage.

PMID- 9591756
TI  - The Trp64Arg mutation of the beta3-adrenergic receptor is associated with
      hyperglycemia and current body mass index in Jamaican women.
AB  - The Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR) has been linked
      to earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), insulin
      resistance, abdominal obesity, and an increased capacity to gain weight in some
      European and Japanese populations. We studied the prevalence of the mutation and
      its association with NIDDM and obesity in our population, in which both rates are
      high, especially in women. The frequency of the homozygous mutation was 1.53%,
      and of the Arg allele, 10.5%. Rates were similar in men and women. Significantly
      higher body mass index (BMI), weight, hip circumference, and fasting and
      postchallenge 2-hour blood glucose concentrations were associated with the
      presence of the Arg allele in women but not in men. The association with weight
      and hip measurements and with hyperglycemia was present only in women aged less
      than 55 years. In multivariate analysis, the mutation was associated with the BMI
      and sex in a model that also included age. The variation in fasting and 2-hour
      blood glucose levels was predicted by beta3-AR, gender, age, and BMI. These
      results suggest that the presence of the mutation contributes to obesity and
      hyperglycemia in our female population.

PMID- 9591757
TI  - Angiotensin-1-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and
      their association with the metabolic syndrome and electrocardiographic coronary
      artery disease in Pima Indians.
AB  - In Caucasian subjects, an insertion/deletion (I/D) polymorphism of the
      angiotensin-converting enzyme (ACE) gene is associated with coronary artery
      disease (CAD) and fatal myocardial infarction. The underlying mechanism(s) of
      this association is not fully understood. Pima Indians have a low incidence of
      nonfatal and fatal CAD despite a high prevalence of diabetes. In Pima Indians,
      circulating ACE levels are related to ACE genotype, but the frequency of the D
      allele is significantly lower than in Caucasians. A lower frequency of the D
      allele may underlie a low risk of CAD in this population. We examined the
      relationship of the ACE genotype and plasma ACE level with electrocardiographic
      evidence of CAD (Tecumseh criteria), hypertension, and metabolic variables
      associated with insulin resistance in 305 (146 men and 159 women aged 47+/-9.0
      years) Pima Indians characterized for the ACE I/D genotype. The distribution of
      ACE genotypes was unrelated to diabetes and obesity. Fasting plasma insulin,
      plasminogen activator inhibitor-1 (PAI-1) activity, plasma triglyceride
      concentrations, and systolic (SBP) and diastolic (DBP) blood pressure were not
      significantly different between the three ACE genotypes among nondiabetic and
      diabetic subjects. There was no significant association of ACE genotype with
      electrocardiographic evidence of CAD or with hypertension. Plasma ACE
      concentrations were not significantly different between nondiabetic and diabetic
      subjects (median, 77 [range, 21 to 1691 v 83 [7 to 238] IU/mL, P=NS). In all
      subjects, plasma ACE levels were associated weakly with plasma triglyceride
      (partial r=.20, P < .01) and total cholesterol (partial r=.13, P <.03)
      concentrations, but not with fasting plasma insulin or PAI-1 activity. In
      diabetic subjects, ACE levels were related to fasting plasma glucose
      concentrations (partial r=.15, P=.07). These findings would suggest that ACE gene
      I/D polymorphism is unlikely to be a major determinant of susceptibility to CAD
      in Pima Indians. Plasma ACE levels, but not ACE genotype, correlated with lipids,
      plasma glucose, and blood pressure, suggesting that elevated plasma ACE levels
      may contribute to the link between insulin resistance and CAD disease or may be a
      consequence of it.

PMID- 9591758
TI  - Antibiotic treatment of Chlamydia pneumoniae for secondary prevention of
      cardiovascular events.

PMID- 9591759
TI  - Inflammation, infection, and cardiovascular risk: how good is the clinical
      evidence?

PMID- 9591760
TI  - Association of virulent Helicobacter pylori strains with ischemic heart disease.
AB  - BACKGROUND: Previous studies have reported an association between chronic
      Helicobacter pylori infection and ischemic heart disease. However, it is not
      clear whether this association is really due to the virulence of the bacterium or
      is merely the result of confounding factors (in particular, age and social
      class). METHODS AND RESULTS: We assessed the prevalence of infection by
      Helicobacter pylori and by strains bearing the cytotoxin-associated gene-A
      (CagA), a strong virulence factor, in 88 patients with ischemic heart disease
      (age, 57+/-8 years; 74 men) and in 88 age- and sex-matched controls (age, 57+/-8
      years; 74 men) with similar social background. Prevalence of Helicobacter
      infection was significantly higher in patients than in controls (62% versus 40%;
      P=.004), with an odds ratio of 2.8 (95% CI, 1.3 to 7.4; P<.001) adjusted for age,
      sex, main cardiovascular risk factors, and social class. Patients with ischemic
      heart disease also had a higher prevalence of CagA-positive strains (43% versus
      17%; P=.0002), with an adjusted odds ratio of 3.8 (95% CI, 1.6 to 9.1; P<.001).
      Conversely, prevalence of CagA-negative strains was similar in patients and
      controls (19% versus 23%), with an adjusted odds ratio of 0.8 (95% CI, 0.4 to
      1.4). CONCLUSIONS: The association between Helicobacter pylori and ischemic heart
      disease seems to be due to a higher prevalence of more virulent Helicobacter
      strains in patients. These results support the hypothesis that Helicobacter
      pylori may influence atherogenesis through low-grade, persistent inflammatory
      stimulation.

PMID- 9591761
TI  - Pharmacodynamic profile of short-term abciximab treatment demonstrates prolonged
      platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade.
AB  - BACKGROUND: The glycoprotein (GP) IIb/IIIa receptor antagonist abciximab is
      approved for use in high-risk percutaneous coronary interventions. The purpose of
      the present study was to establish the pharmacodynamic profile and platelet-bound
      life span of abciximab. METHODS AND RESULTS: The pharmacodynamics of abciximab
      (inhibition of ex vivo platelet aggregation and GP IIb/IIIa receptor blockade)
      were measured in 41 individuals who were randomized to receive a 0.25-mg/kg bolus
      and a 12-hour infusion of either 10 microg/min (EPIC regimen) or 0.125 microg x
      kg(-1) x min(-1) (EPILOG regimen) of the antiplatelet agent. At extended times,
      the amount and distribution of platelet-bound abciximab were monitored by flow
      cytometry. The EPIC and EPILOG infusion regimens exhibited equivalent blockade of
      both GP IIb/IIIa receptors and platelet aggregation throughout the duration of
      abciximab treatment. Flow cytometry revealed a single, highly fluorescent
      platelet population during treatment, consistent with complete saturation and
      homogeneous distribution of abciximab on circulating platelets. For 15 days after
      treatment, the fluorescence histograms remained unimodal with gradually
      diminishing fluorescence intensity, indicating decreasing levels of platelet
      bound abciximab. At 8 and 15 days, which exceeds the normal circulating life span
      of platelets, median relative fluorescence intensity corresponded to 29100 (29%
      GP IIb/IIIa receptor blockade) and 13300 (13% GP IIb/IIIa receptor blockade)
      abciximab molecules bound per platelet, respectively. CONCLUSIONS: These results
      are consistent with continuous reequilibration of abciximab among circulating
      platelets and may explain the gradual recovery of platelet function and long-term
      prevention of ischemic complications by abciximab after coronary intervention.

PMID- 9591762
TI  - Obesity and risk of adverse outcomes associated with coronary artery bypass
      surgery. Northern New England Cardiovascular Disease Study Group.
AB  - BACKGROUND: Obesity is frequently cited as a risk factor for adverse outcomes of
      major surgery. The results of prior studies of the relationship between obesity
      and risk of adverse outcomes of coronary artery bypass grafting (CABG) have been
      contradictory because of insufficient power to assess relatively infrequent
      outcomes or data to adjust for confounding factors. METHODS AND RESULTS: Data on
      patient age, sex, height, weight, medical history, current clinical status, and
      treatment factors were assessed prospectively among 11101 consecutive patients
      undergoing CABG. Body mass index (BMI) was used as the measure of obesity and was
      categorized as nonobese (1st to 74th percentiles), obese (75th to 94th
      percentiles), or severely obese (95th to 100th percentiles). Adverse outcomes
      occurring in-hospital, including mortality, intraoperative/postoperative
      cerebrovascular accident (CVA), postoperative bleeding, and sternal wound
      infection, were defined prospectively. Associations between obesity and
      postoperative outcomes were assessed by use of logistic regression to adjust for
      potentially confounding variables. Although obesity was not associated with
      increased mortality (adjusted odds ratio [OR], 1.16; P=.261) or postoperative CVA
      (adjusted OR, 1.06; P=.765), risks of sternal wound infection were substantially
      increased in the obese (adjusted OR, 2.10; confidence interval [CI], 1.45 to
      3.06; P<.001) and severely obese (adjusted OR, 2.74; CI, 1.49 to 5.02; P=.001).
      On the other hand, rates of postoperative bleeding were significantly lower in
      the obese (adjusted OR, 0.66; CI, 0.49 to 0.90; P=.009) and severely obese
      (adjusted OR, 0.40; CI, 0.20 to 0.81; P=.011). CONCLUSIONS: With the exception of
      sternal wound infection, the perception among clinicians that obesity predisposes
      to various postoperative complications with CABG is not supported by these data.
      Further work is needed to understand the apparent protective effect of obesity on
      risks of postoperative bleeding.

PMID- 9591763
TI  - Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in
      vivo.
AB  - BACKGROUND: Endothelial function is impaired in patients with diabetes mellitus.
      However, the factors contributing to this defect are currently unknown.
      Hyperglycemia attenuates endothelium-dependent relaxation in normal rabbit
      arteries in vitro and rat arterioles in vivo. Accordingly, this study examined
      the effect of acute hyperglycemia on endothelium-dependent vasodilation in
      nondiabetic humans in vivo. METHODS AND RESULTS: Endothelium-dependent
      vasodilation was assessed through brachial artery infusion of methacholine
      chloride both before and during 6 hours of local hyperglycemia (300 mg/dL)
      achieved by intra-arterial infusion of 50% dextrose. Forearm blood flow was
      determined by plethysmography. In a group of 10 subjects, there was a trend
      toward attenuated methacholine-mediated vasodilation during hyperglycemia
      compared with euglycemia (P=.07 by ANOVA; maximal response, 13.3+/-2.8 versus
      14.7+/-1.5 mL x min(-1) x 100 mL(-1), respectively). In these subjects, the
      systemic serum insulin levels increased significantly during the dextrose
      infusion (P<.001). To eliminate the confounding vasoactive effects of insulin,
      the protocol was repeated during systemic infusion of octreotide (30 ng x kg(-1)
      x min(-1)) to inhibit pancreatic secretion of insulin. In these subjects (n=10),
      hyperglycemia significantly attenuated the forearm blood flow response to
      methacholine (P<.01 by ANOVA; maximal response, 16.9+/-2.5 before versus 12.7+/
      1.8 mL x min(-1) x 100 mL(-1) during hyperglycemia). Methacholine-mediated
      vasodilation was not attenuated by an equimolar infusion of mannitol (P>.40), nor
      did hyperglycemia reduce endothelium-independent vasodilation to verapamil
      (P>.50). CONCLUSIONS: Acute hyperglycemia impairs endothelium-dependent
      vasodilation in healthy humans in vivo. This finding suggests that elevated
      glucose may contribute to the endothelial dysfunction observed in patients with
      diabetes mellitus.

PMID- 9591764
TI  - Economic assessment of low-molecular-weight heparin (enoxaparin) versus
      unfractionated heparin in acute coronary syndrome patients: results from the
      ESSENCE randomized trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q
      wave Coronary Events [unstable angina or non-Q-wave myocardial infarction].
AB  - BACKGROUND: In the ESSENCE trial, subcutaneous low-molecular-weight heparin
      (enoxaparin) reduced the 30-day incidence of death, myocardial infarction, and
      recurrent angina relative to intravenous unfractionated heparin in 3171 patients
      with acute coronary syndrome (unstable angina or non-Q-wave myocardial
      infarction). No increase in major bleeding was seen. METHODS AND RESULTS: Of the
      936 ESSENCE patients randomized in the United States, 655 had hospital billing
      data collected. For the remainder, hospital costs were imputed with a
      multivariable linear regression model (R2=.86). Physician fees were estimated
      from the Medicare Fee Schedule. During the initial hospitalization, major
      resource use was reduced for enoxaparin patients, with the largest effect seen
      with coronary angioplasty (15% versus 20% for heparin, P=.04). At 30 days, these
      effects persisted, with the largest reductions seen in diagnostic catheterization
      (57% versus 63% for heparin, P=.04) and coronary angioplasty (18% versus 22%,
      P=.08). All resource use trends seen in the US cohort were also evident in the
      overall ESSENCE study population. In the United States, the mean cost of a course
      of enoxaparin therapy was $155, whereas that for heparin was $80. The total
      medical costs (hospital, physician, drug) for the initial hospitalization were
      $11 857 for enoxaparin and $12620 for heparin, a cost advantage for the
      enoxaparin arm of $763 (P=.18). At the end of 30 days, the cumulative cost
      savings associated with enoxaparin was $1172 (P=.04). In 200 bootstrap samples of
      the 30-day data, 94% of the samples showed a cost advantage for enoxaparin.
      CONCLUSIONS: In patients with acute coronary syndrome, low-molecular-weight
      heparin (enoxaparin) both improves important clinical outcomes and saves money
      relative to therapy with standard unfractionated heparin.

PMID- 9591765
TI  - Increased matrix metalloproteinase activity and selective upregulation in LV
      myocardium from patients with end-stage dilated cardiomyopathy.
AB  - BACKGROUND: One of the hallmarks of dilated cardiomyopathy (DCM) is left
      ventricular (LV) remodeling. The matrix metalloproteinases (MMPs) are a family of
      enzymes that contribute to extracellular remodeling in several disease states.
      Additionally, a family of inhibitors called tissue inhibitors of MMPs (TIMPs) has
      been shown to exist and to tightly regulate MMP activity. However, the types of
      MMPs and TIMPs expressed within the normal and DCM LV myocardium and the relation
      to MMP activity remain unexplored. METHODS AND RESULTS: Relative LV myocardial
      MMP activity was determined in the normal (n=8) and idiopathic DCM (n=7) human LV
      myocardium by substrate zymography. Relative LV myocardial abundance of
      interstitial collagenase (MMP-1), stromelysin (MMP-3), 72 kD gelatinase (MMP-2),
      92 kD gelatinase (MMP-9), TIMP-1, and TIMP-2 were measured with quantitative
      immunoblotting. LV myocardial MMP zymographic activity increased with DCM
      compared with normal (984+/-149 versus 413+/-64 pixels, P<.05). With DCM, LV
      myocardial abundance of MMP-1 decreased to 16+/-6% (P<.05), MMP-3 increased to
      563+/-212% (P<.05), MMP-9 increased to 422+/-64% (P<.05), and MMP-2 was unchanged
      when compared with normal. LV myocardial abundance of TIMP-1 and TIMP-2 increased
      by >500% with DCM. A high-molecular-weight immunoreactive band for both TIMP-1
      and TIMP-2, suggesting a TIMP/MMP complex, was increased >600% with DCM.
      CONCLUSIONS: This study demonstrated increased LV myocardial MMP activity and
      evidence for independent regulatory mechanisms of MMP and TIMP expression with
      DCM. These findings suggest that selective inhibition of MMP species within the
      LV myocardium may provide a novel therapeutic target in patients with DCM.

PMID- 9591766
TI  - Mitral regurgitation: impaired systolic function, eccentric hypertrophy, and
      increased severity are linked to lower phosphocreatine/ATP ratios in humans.
AB  - BACKGROUND: A number of phosphorus (31P) magnetic resonance spectroscopy (MRS)
      studies link alterations of high-energy phosphate metabolism in valvular disease
      and cardiomyopathy to the clinical severity of heart failure. However,
      correlations between MRS and indexes of ventricular dysfunction are inconclusive
      to date. We examined whether changes in 31P MRS are associated with the impaired
      contractility, which predisposes to chronic congestive heart failure in patients
      with mitral regurgitation. METHODS AND RESULTS: Thirteen normal control subjects
      and 22 patients with echocardiographically characterized chronic mitral
      regurgitation were studied by 31P MRS. The apical phosphocreatine-to-ATP ratio
      (PCr/ATP) was lower in severe disease (P<.02) and those on therapy (n=13, 1.29+/
      0.29, P<.01) in contrast to control subjects (n=13, 1.61+/-0.3). Compared to
      those with mild mitral regurgitation, patients with more severe incompetence had
      lower mean myocardial PCr/ATP ratios (mild, n=6, 1.73 [0.17], P<.05 and P<.01;
      moderate, n=5, 1.49 [0.18], P<.05; and severe, n=1, 1.29 [0.32], P<.01). PCr/ATP
      in those referred for mitral valve replacement was lower (n=8, 1.17+/-0.23)
      although not significantly decreased compared with the ratio among subjects on
      medical therapy alone (n=5, 1.48+/-0.29). PCr/ATP correlated with the end
      systolic diameter (r2=.7, P<.001), end-diastolic diameter (r2=.32, P<.05), left
      ventricular wall thickness (r2=.38, P<.01), left atrial dimension (r2=.36,
      P<.05), and derived measurements such as the percent fractional shortening (2=.5,
      P<.01), and left ventricular mass/body surface area (r2=.5, P<.001) but not with
      wall stress. CONCLUSIONS: These results demonstrate that abnormalities of PCr/ATP
      in mitral regurgitation are related to disease severity as measured by
      dimensional indexes of left ventricular dilatation. They suggest that impaired
      high-energy phosphate metabolism is a marker of hypertrophy and heart failure.

PMID- 9591767
TI  - Cellular uncoupling during ischemia in hypertrophied and failing rabbit
      ventricular myocardium: effects of preconditioning.
AB  - BACKGROUND: Patients with heart failure show a very high incidence of arrhythmias
      and sudden death that is often preceded by ischemia; however, data on
      electrophysiological changes during ischemia in failing myocardium are sparse. We
      studied electrical uncoupling during ischemia in normal and failing myocardium.
      METHODS AND RESULTS: Tissue resistance, intracellular Ca2+ concentration (Indo-1
      fluorescence ratio), and mechanical activity were simultaneously determined in
      arterially perfused right ventricular papillary muscles from 11 normal and 15
      failing rabbits. Heart failure was induced by combined volume and pressure
      overload. Before sustained ischemia, muscles were subjected to control perfusion
      (non-PC) or ischemic preconditioning (PC). The onset of uncoupling during
      ischemia was equal in non-PC normal (13.6+/-0.9 minutes of ischemia) and non-PC
      failing hearts (13.3+/-0.7 minutes of ischemia). PC postponed uncoupling in
      normal hearts by 10 minutes. In failing hearts, however, PC caused a large
      variability in the onset of uncoupling during ischemia (mean, 12.2+/-2.1; range,
      5 to 22 minutes of ischemia). The duration of uncoupling process was prolonged in
      failing hearts (12.9+/-0.9 minutes) compared with normal hearts (7.8+/-0.4
      minutes). The degree of heart failure and relative heart weight of the failing
      hearts significantly correlated with the earlier uncoupling after PC and the
      duration of uncoupling. In every experiment, the start of Ca2+ rise and
      contracture preceded uncoupling during ischemia. CONCLUSIONS: The duration of the
      process of ischemia-induced electrical uncoupling in failing hearts is prolonged
      compared with that in normal hearts. Ischemic PC has detrimental effects in
      severely failing papillary muscles because it advances the moment of irreversible
      ischemic damage.

PMID- 9591768
TI  - Angiotensin blockade inhibits activation of mitogen-activated protein kinases in
      rat balloon-injured artery.
AB  - BACKGROUND: The effect of balloon injury on the arterial signal transduction
      pathway has not been examined. In vitro studies show that extracellular signal
      regulated kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs), belonging to the
      mitogen-activated protein kinase (MAPK) family, play a critical role in the
      activation of transcription factor activator protein-1 (AP-1) and cell
      proliferation or apoptosis. However, the activation and role of MAPKs in vascular
      diseases in vivo remain to be determined. Therefore, we examined the effect of
      balloon injury on arterial MAPKs and the possible role of angiotensin II. METHODS
      AND RESULTS: Arterial JNK and ERK activities were measured by in-gel kinase
      assay. AP-1 DNA binding activity was determined by gel mobility shift analysis.
      After balloon injury of rat carotid artery, JNK (p46JNK and p55JNK) and ERK
      (p44ERK and p42ERK) activities were increased as early as 2 minutes, reached
      their peak (6- to 18-fold) at 5 minutes, and thereafter rapidly declined to
      control levels. JNK and ERK activations were followed by a 3.9-fold increase in
      arterial AP-1 DNA binding activity, which contained c-Jun and c-Fos proteins.
      Arterial JNK activation at 2 or 5 minutes was remarkably suppressed by E4177 (an
      angiotensin AT1 receptor antagonist) and cilazapril (an ACE inhibitor). E4177
      also prevented activation of ERKs by suppressing their tyrosine phosphorylation,
      whereas cilazapril failed to prevent such activation. The increased AP-1 DNA
      binding activity was significantly inhibited by both E4177 and cilazapril.
      CONCLUSIONS: Arterial JNKs and ERKs are dramatically activated by balloon injury
      associated with the activation of the AP-1 complex. These MAPK activations,
      followed by AP-1 activation, are mediated at least in part by the AT1 receptor.
      Thus, activation of JNKs and ERKs may be responsible for balloon injury-induced
      neointima formation.

PMID- 9591769
TI  - Myocardial discontinuities: a substrate for producing virtual electrodes that
      directly excite the myocardium by shocks.
AB  - BACKGROUND: Theoretical models suggest that an electrical stimulus causes regions
      of depolarization and hyperpolarization on either side of a myocardial
      discontinuity. This study determined experimentally whether an artificial
      discontinuity gives rise to an activation front in response to an electrical
      stimulus, consistent with the creation of such polarized regions. METHODS AND
      RESULTS: After a thoracotomy in six dogs, a 504-unipolar-electrode plaque was
      sutured to the right ventricular epicardium to map activations. From a line
      electrode parallel to one side of the plaque, 10 S1 stimuli were delivered,
      followed by S2 and S3 stimuli (S1S1, S1S2, S2S3 interval=300 ms). S1 and S3
      stimuli were 25 mA; 5-ms S2 stimuli of both polarities were initially 25 mA and
      increased in 25 mA increments. The plaque was removed, and a transmural incision
      was made through the ventricular wall in the middle of the mapped region and
      sutured closed. The plaque was replaced and the stimulation protocol repeated.
      Before the incision, S2 stimuli directly activated tissue only near the
      stimulation site. An activation front arose at the border of the directly
      activated region and propagated across the plaque. As the S2 stimulus strength
      was increased, the size of the directly activated region increased. After the
      incision, sufficiently large S2 stimuli caused direct activation of tissue
      adjacent to the transmural incision as well as at the stimulation site.
      Activation fronts that arose adjacent to the transmural incision either
      propagated proximally toward the stimulation site and collided with the
      activation front originating from the stimulation wire or propagated distally
      away from the incision. Minimum S2 stimulus strengths activating areas adjacent
      to the incision were only 45+/-14% (cathode) and 39+/-18% (anode) of the
      strengths required to directly activate the same area before the incision was
      formed (P<.05). CONCLUSIONS: Myocardial discontinuities can give rise to
      activation fronts after a stimulus, suggesting the presence of polarized regions
      adjacent to the discontinuity.

PMID- 9591770
TI  - Myocardial architecture and ventricular arrhythmogenesis.

PMID- 9591771
TI  - Images in cardiovascular medicine. Successful transcatheter retrieval of an air
      gun pellet and adherent thrombus from a pulmonary artery branch.

PMID- 9591772
TI  - Images in cardiovascular medicine. Coronary artery bypass graft surgery of 77
      year-old woman.

PMID- 9591773
TI  - Development of highly selective SH3 binding peptides for Crk and CRKL which
      disrupt Crk-complexes with DOCK180, SoS and C3G.
AB  - Many Src Homology 3 (SH3) domains function as molecular adhesives in
      intracellular signal transduction. Based on previous ultrastructural studies,
      short motifs which bind to the first SH3 domains of the adapters Crk and CRKL
      were selectively mutagenised to generate Crk/CRKL SH3-binding peptides of very
      high affinity and selectivity. Affinities were increased up to 20-fold compared
      to the best wildtype sequences, while the selectivity against a similar SH3
      domain [Grb2SH3(N)] was not only retained, but sometimes increased. Blot
      techniques with GST-fusion peptides and in solution precipitation assays with
      biotinylated high affinity Crk binding peptides (HACBPs) were subsequently used
      to analyse the binding of these sequences to a large panel of SH3 domain
      containing fusion proteins. Only those proteins which contained the CrkSH3(1) or
      CRKLSH3(1) domains bound efficiently to the HACBPs. A GST-HACBP fusion protein
      precipitated Crk and CRKL proteins out of 35S-labelled and unlabelled cell
      lysates. Very little binding of other cellular proteins to HACBP was detectable,
      indicative of a great preference for Crk and CRKL when compared to the wide
      variety of other endogenous cellular proteins. Moreover, HACBP disrupted in vitro
      preexisting Crk-complexes with DOCK180 and the exchange factors SoS and C3G,
      which are known targets of Crk adapters, in a concentration dependent manner.
      HACBP-based molecules should therefore be useful as highly selective inhibitors
      of intracellular signalling processes involving Crk and CRKL.

PMID- 9591774
TI  - Increased cell growth and tumorigenicity in human prostate LNCaP cells by
      overexpression to cyclin D1.
AB  - Deregulated expression of cyclin D1 has been found in several types of human
      tumors. In order to investigate factors involved in human prostate cancer
      progression, we studied the effects of cyclin D1 overexpression on human prostate
      cancer cell proliferation and tumorigenicity by transfecting LNCaP cells with a
      retroviral vector containing human cyclin D1 cDNA. When compared to the parental
      and control-vector transfected LNCaP cells, these cyclin D1-transfected cells had
      more cells in S-phase and lower growth factor requirements. Furthermore, these
      cells grew more in androgen-free medium. We also detected higher levels of Rb
      phosphorylation and E2F-1 protein levels in LNCaP/cyclin D1 cells than that in
      the parental and vector control cells in medium with or without androgen. Cyclin
      D1 transfected clones formed tumors more rapidly than control and parental cells.
      These tumors were refractory to the androgen-ablation treatment by castration,
      whereas tumors from parental and vector-control LNCaP cells regressed within 4
      weeks after castration. These results suggest that overexpression of cyclin D1
      changes the growth properties, increases tumorigenicity and decreases the
      requirement for androgen stimulation in LNCaP cells both in vitro and in vivo.

PMID- 9591775
TI  - Characterization of transformation related genes in oral cancer cells.
AB  - A cDNA representational difference analysis (cDNA-RDA) and an arrayed filter
      technique were used to characterize transformation-related genes in oral cancer.
      From an initial comparison of normal oral epithelial cells and a human papilloma
      virus (HPV)-immortalized oral epithelial cell line, we obtained 384
      differentially expressed gene fragments and arrayed them on a filter. Two hundred
      and twelve redundant clones were identified by three rounds of back
      hybridization. Sequence analysis of the remaining clones revealed 99 unique
      clones corresponding to 69 genes. The expression of these transformation related
      gene fragments in three nontumorigenic HPV-immortalized oral epithelial cell
      lines and three oral cancer cell lines were simultaneously monitored using a cDNA
      array hybridization. Although there was a considerable cell line-to-cell line
      variability in the expression of these clones, a reliable prediction of their
      expression could be made from the cDNA array hybridization. Our study
      demonstrates the utility of combining cDNA-RDA and arrayed filters in high
      throughput gene expression difference analysis. The differentially expressed
      genes identified in this study should be informative in studying oral epithelial
      cell carcinogenesis.

PMID- 9591777
TI  - Loss of protein kinase C function induces an apoptotic response.
AB  - A correlation has been observed between the dephosphorylation and downregulation
      of cPKC and the induction of apoptosis. This relationship is shown to be causal
      in COS cells where expression of dominant negative PKC alpha is shown to induce
      apoptosis. This response is rescued by co-expression of wild-type PKC alpha. The
      results demonstrate that PKC provides a survival signal that can be supplied by
      PKC alpha alone.

PMID- 9591776
TI  - Retinoblastoma protein associates with SP1 and activates the hamster
      dihydrofolate reductase promoter.
AB  - The dihydrofolate reductase (dhfr) promoter is powerfully activated by the
      transcription factor Sp1. It has been suggested that Sp1 is a potential target
      for transcriptional regulation by the cell cycle regulator retinoblastoma protein
      (Rb), and so we have explored this possibility using the hamster dhfr gene as a
      model. By the use of DNA probes from the hamster dhfr gene promoter, containing
      the most proximal GC box (minimal promoter), and nuclear extracts from cultured
      hamster cells (CHO K1), we show that polyclonal and monoclonal antibodies against
      Rb supershift the binding of Sp1. Nuclear extract immunoprecipitation with anti
      Rb followed by Western analysis using anti-Sp1 also shows that Rb is complexed to
      Sp1. Complementary Immunoprecipitation/WB analysis shows both forms of Rb protein
      in the anti-Sp1 immunoprecipitates. Moreover, nuclear extract immunodepletion of
      Rb abolishes Sp1 gel-shift. The interaction between Rb and Sp1 is maintained in
      all the phases of the cell cycle. Transient overexpression of Rb in dhfr negative
      cells co-transfected with a dhfr minigene driven by its minimal promoter
      increases DHFR activity and potentiates transcription when overexpressing Sp1.
      Both effects are severely reduced when the co-transfections are performed with a
      homologous dhfr minigene containing a single point mutation in the GC box. Thus,
      the activation by Rb of the dhfr gene may be exerted through Sp1. Stable
      transfectants of pCMVRb in K1 cells show an increase in both mRNA and DHFR
      activity. It is concluded that Sp1 is physically associated with Rb, and that
      this association increases Sp1-mediated transcription of the hamster dhfr gene.

PMID- 9591778
TI  - The acute promyelocytic leukaemia specific PML and PLZF proteins localize to
      adjacent and functionally distinct nuclear bodies.
AB  - Acute promyelocytic leukaemia is characterized by translocations that involve the
      retinoic acid receptor alpha (RAR alpha) locus on chromosome 17 and the PML locus
      on 15 or the PLZF locus on 11. The resulting abnormal translocation products
      encode for PML/RAR alpha or PLZF/RAR alpha fusion proteins. There is increasing
      experimental evidence that the APL-specific fusion proteins have similar biologic
      activities on differentiation and survival and that both components of the fusion
      proteins (PML or PLZF and RAR alpha) are indispensable for these biological
      activities. The physiologic function of PML or PLZF or whether PML and PLZF
      contribute common structural or functional features to the corresponding fusion
      proteins is not known. We report here immunofluorescence studies on the cellular
      localization of PLZF and PLZF/RAR alpha and compare it with the localization of
      PML and PML/RAR alpha. PLZF localizes to nuclear domains of 0.3-0.5 microns,
      approximately 14 per cell in the KG1 myeloid cell line. These PLZF-bodies are
      morphologically similar to the domains reported for PML (PML-NBs). There is tight
      spatial relationship between about 30% of PLZ-NBs and PML-NBs: they partially
      overlap. However, PML and PLZF do not form soluble complexes in vivo. PLZF- and
      PML-NBs are functionally distinct. Adenovirus E4-ORF3 protein expression alters
      the structure of the PML-NBs and interferon increases the number of PML-NBs and
      neither has any effect on PLZF NBs. The localization of PLZF/RAR alpha is
      different to that of PLZF and RAR alpha. The nuclear distribution pattern of
      PLZF/RAR alpha is one of hundreds of small dots (microspeckles) less than 0.1
      micron. Expression of PLZF/RAR alpha did not provoke disruption of the PML-NBs.
      Co-expression of PML/RAR alpha and PLZF/RAR alpha in U937 cells revealed apparent
      colocalization. Overall the results suggest that the PML- and PLZF-NBs are
      distinct functional nuclear domains, but that they may share common regulatory
      pathways and/or targeting sequences, as revealed by the common localization of
      their corresponding fusion proteins.

PMID- 9591779
TI  - Correlation of B-FABP and GFAP expression in malignant glioma.
AB  - The murine brain fatty acid binding protein (B-FABP) is encoded by a
      developmentally regulated gene that is expressed in radial glial cells and
      immature astrocytes. We have cloned the human B-FABP gene and have mapped it to
      chromosome 6q22-23. We show that B-FABP mRNA is expressed in human malignant
      glioma tumor biopsies and in a subset of malignant glioma cell lines, as well as
      in human fetal retina and brain. Malignant glioma tumors are characterized by
      cytoplasmic bundles of glial fibrillary acidic protein (GFAP), a protein normally
      expressed in mature astrocytes. Establishment of malignant glioma cell lines
      often results in loss of GFAP. The subset of malignant glioma cell lines that
      express GFAP mRNA also express B-FABP mRNA. Co-localization experiments in cell
      lines indicate that the same cells produce both GFAP and B-FABP. We suggest that
      some malignant gliomas may be derived from astrocytic precursor cells which can
      express proteins that are normally produced at different developmental stages in
      the astrocytic differentiation pathway.

PMID- 9591780
TI  - The induction of uterine leiomyomas and mammary tumors in transgenic mice
      expressing polyomavirus (PyV) large T (LT) antigen is associated with the ability
      of PyV LT antigen to form specific complexes with retinoblastoma and CUTL1 family
      members.
AB  - The inactivation of certain tumor suppressor genes is thought to play an
      important role in the genesis of a number of tumor types. For example,
      inactivation of the Retinoblastoma (Rb) tumor suppressor is frequently observed
      in a proportion of sporadic human breast cancers. While these studies suggest
      that inactivation of key tumor suppressor genes may play an important role in the
      induction of mammary cancers, direct evidence supporting this contention is
      lacking. Because polyomavirus (PyV) Large T (LT) antigen is known to associate
      with and inactivate certain members of the Rb family (p105Rb, p107, p130), we
      have derived transgenic mice which express PyV LT antigen in the mammary
      epithelium. As expected mammary epithelial-specific expression of PyV LT antigen
      resulted in the induction of mammary tumors which correlated with their capacity
      to associate with Rb family members. In addition to mammary carcinomas, female
      transgenic mice expressing the PyV LT transgene frequently develop uterine
      leiomyomas. Because loss of heterozygosity involving the human CUTL1 (Cut like 1)
      gene located at chromosomal position 7q22 has been recently implicated in
      sporadic human uterine leiomyomas, we tested the hypothesis that PyV LT antigen
      may also form specific complexes with CUTL1. The results of these analyses
      revealed that specific complexes of CUTL1 and PyV LT antigen could be detected in
      both leiomyomas and mammary tumors. Taken together, these observations suggest
      that PyV LT antigen may be involved in inducing these tumors by sequestering both
      CUTL1 and Rb growth regulatory proteins.

PMID- 9591781
TI  - The desmoplastic small round cell tumor t(11;22) translocation produces EWS/WT1
      isoforms with differing oncogenic properties.
AB  - Structural alterations of the Wilms' tumor locus (WT1) at 11p13 have been
      implicated in the etiology of two human cancers--Wilms' tumor (WT), a pediatric
      renal malignancy, and Desmoplastic Small Round Cell Tumor (DSRCT), an aggressive
      cancer of the abdominal serosal lining with predilection for male adolescents.
      Germline mutations within the WT1 tumor suppressor gene predispose to WT and are
      associated with congenital malformations of the urogenital system, and somatic
      mutations are associated with initiation of transformation in WTs. In DSRCT, a
      recurrent translocation, t(11;22)(p13;q12), fuses the amino terminal domain of
      the EWS1 gene product to three of the four WT1 zinc fingers. Two EWS/WT1 isoforms
      are generated as a result of an alternative splicing event between zinc fingers
      III and IV, inserting or removing three amino acids (+/- KTS). We demonstrate
      that introduction of EWS/WT1(-KTS) into NIH3T3 cells causes their tumorigenic
      transformation as determined by: formation of transformed foci on a monolayer of
      cells; anchorage-independent growth; and tumor formation in nude mice.
      EWS/WT1(+KTS) showed no transforming potential in these assays. These results
      indicate the oncogenic effect of the t(11;22) translocation is mediated by the
      EWS/WT1(-KTS) isoform and that fusion of the EWS amino terminal domain to the WT1
      DNA binding domain produces a chimeric product showing a gain of function.

PMID- 9591783
TI  - Identification of an allosteric binding site on the transcription factor p53
      using a phage-displayed peptide library.
AB  - Monoclonal antibody PAb1620 recognizes a conformational epitope on the
      transcription factor p53 and, upon binding, allosterically inhibits p53 binding
      to DNA. A highly diverse (1.5 x 10(10) members) phage-displayed library of
      peptides containing 40 random amino acids was used to identify the PAb1620
      binding site on p53. Panning this library against PAb1620 resulted in three
      unique peptides which have statistically significant sequence identities with p53
      sufficient to identify the binding site as being composed of amino acids 106-113
      and 146-156. Based on these results, we propose a mechanism by which PAb1620 can
      allosterically inhibit p53 binding to DNA through an indirect interaction between
      the antibody binding site and the L1 loop (amino acids 112-124) of p53, which is
      a component of the DNA binding region.

PMID- 9591782
TI  - Insulin-like growth factor-1 stimulates rat prolactin gene expression by a Ras,
      ETS and phosphatidylinositol 3-kinase dependent mechanism.
AB  - We have examined the influence of insulin-like growth factor I (IGF-1) on
      prolactin gene expression in rat pituitary GH4C1 cells. Incubation with IGF-1
      increases prolactin mRNA levels and activates the prolactin promoter in transient
      transfection assays. A similar degree of activation is observed with constructs
      extending to -3000 and -176 base pairs of the prolactin 5' flanking region,
      indicating that the IGF-1 response element is located in the proximal promoter
      sequences. A plasmid containing 101 base pairs shows a partial stimulation by IGF
      1, and the response is lost in a deletion to -76 base pairs. The Ras oncoproteins
      have been implicated as a critical signaling component in mediating the effect of
      growth factor receptor tyrosine kinases. Expression of oncogenic RasVal12 mimics
      the effect of IGF-1 on the prolactin promoter, and a dominant negative Ras,
      RasAsn17, blocks IGF-1-mediated stimulation. Dominant negative mitogen-activated
      protein kinase (MAPK) also reduces the activation of the prolactin promoter by
      IGF-1. Ets transcription factors have been described to lie downstream of Ras and
      MAPK in the signaling pathway leading to prolactin gene activation. Mutation of
      two Ets binding sites in the promoter region between -101 and -76 abolishes the
      response to IGF-1. Furthermore, a dominant negative Ets vector strongly reduces
      the response of the prolactin promoter to IGF-1 and Ras. The endogenous
      concentration of Ets-related proteins is not limiting in GH4C1 cells for the IGF
      1 effect. However, c-Ets-1 and GHF-1 act synergistically in HeLa cells with the
      IGF-1 receptor, reconstituting pituitary IGF-1 responsiveness. The response to
      IGF-1 in GH4C1 cells is still observed after transfection with RasVal12
      suggesting that, although Ras is required, IGF-1 could stimulate other pathway/s
      in addition to Ras. Wortmanin, an inhibitor of phosphatidylinositol-3 kinase (PI
      3 kinase), also prevents the response of the prolactin promoter to IGF-1. These
      results show that both the Ras/MAPK/Ets pathway, as well as the activation of PI
      3 kinase are involved in the signaling mechanism leading to prolactin expression
      by IGF-1 in GH4C1 cells.

PMID- 9591784
TI  - Identification of domains of c-Jun mediating androgen receptor transactivation.
AB  - The proto-oncoprotein c-Jun, when complexed with c-Fos, forms the climeric
      complex identified as AP-1 which regulates transcription directly by binding to
      AP-1-responsive genes. We have previously reported an indirect mechanism by which
      c-Jun is able to regulate transcription by stimulating androgen receptor
      transactivation in the absence of c-Fos or any apparent DNA binding. A series of
      c-Jun mutants were tested in order to characterize the domains of c-Jun
      responsible for this effect. The studies reported here indicate that a functional
      bZIP region and a portion of the N-terminal activation functions is necessary for
      c-Jun stimulation of androgen receptor transactivation. Testing c-Jun/v-Jun
      chimeras, we show that v-Jun is unable to stimulate androgen receptor
      transactivation and the effect is dependent on the c-Jun activation functions. c
      Jun exhibits a bell-shaped activity on androgen receptor-mediated transactivation
      which appears to be distinct from c-Jun's transactivation ability. A c-Jun mutant
      deficient in transactivation is able to stimulate androgen receptor activity.
      These results indicate that c-Jun's transactivation ability can be separated from
      c-Jun's ability to stimulate the androgen receptor transactivation.

PMID- 9591785
TI  - Interaction of Rho1p target Bni1p with F-actin-binding elongation factor 1alpha:
      implication in Rho1p-regulated reorganization of the actin cytoskeleton in
      Saccharomyces cerevisiae.
AB  - The RHO1 gene encodes a homolog of mammalian RhoA small G protein in the yeast
      Saccharomyces cerevisiae. We have shown that Bni1p is one of the downstream
      targets of Rho1p and regulates reorganization of the actin cytoskeleton through
      the interaction with profilin, an actin monomer-binding protein. A Bni1p-binding
      protein was affinity purified from the yeast cytosol fraction and was identified
      to be Tef1p/Tef2p, translation elongation factor 1alpha (EF1alpha). EF1alpha is
      an essential component of the protein synthetic machinery and also possesses the
      actin filament (F-actin)-binding and -bundling activities. EF1alpha bound to the
      186 amino acids region of Bni1p, located between the FH1 domain, the proline-rich
      profilin-binding domain, and the FH2 domain, of which function is not known. The
      binding of Bni1p to EF1alpha inhibited its F-actin-binding and -bundling
      activities. The BNI1 gene deleted in the EF1alpha-binding region did not suppress
      the bni1 bnr1 mutation in which the actin organization was impaired. These
      results suggest that the Rho1p-Bni1p system regulates reorganization of the actin
      cytoskeleton through the interaction with both EF1alpha and profilin.

PMID- 9591786
TI  - Expression of the v-Src oncoprotein in fibroblasts disrupts normal regulation of
      the CDK inhibitor p27 and inhibits quiescence.
AB  - To determine how an oncogenic tyrosine kinase disturbs cell cycle control we
      examined expression of cell cycle proteins and growth of fibroblasts reversibly
      transformed by a temperature sensitive mutant of v-Src (ts LA 29). ts LA 29 Rat-1
      cells and normal Rat-1 cells had similar growth rates but the transformed cells
      traversed the G1 phase of the cell cycle more rapidly and failed to exit cycle
      efficiently in response to serum starvation and cell confluence. Cyclin D1 and
      cyclin E levels were not elevated in growing ts LA 29 Rat-1 cells and the
      abbreviated G1 was further accelerated by overexpression of cyclin E. A fall in
      cyclin E and cyclin A dependent kinase activities in Rat-1 cells in response to
      inhibitory growth conditions was abrogated in ts LA 29 Rat-1 cells and correlated
      with lack of p27 accumulation or cyclin A down regulation, the latter due to
      sustained cyclin A promoter activity. The expression of p27 mRNA was lower in ts
      LA 29 Rat-1 cells than Rat-1 cells and was elevated following v-Src inactivation
      concurrent with an increase in p27 promoter activity and temporary cell cycle
      exit. The suppression of mRNA or transcription is a novel way an oncoprotein can
      induce down regulation of p27 and contributes to the G1 shortening and perturbed
      cell cycle regulation of the v-Src transformed cells.

PMID- 9591787
TI  - Bcr/Abl associated leukemogenesis in bcr null mutant mice.
AB  - The BCR gene contributes to Philadelphia-positive leukemogenesis via a number of
      discrete mechanisms, one of which may be through interaction of its normal gene
      product with the Bcr/Abl oncoprotein. In the current study this hypothesis was
      tested in vivo by introducing a Bcr/Abl P190 transgene into mice lacking
      endogenous bcr protein. Our finding, that the P190 BCR/ABL oncogene is still
      capable of producing leukemia in these mice with indistinguishable latency and
      clinical pattern as in genetically matched counterparts, rules out any
      significant or major contribution of the bcr protein as a whole to leukemia
      development in these mice.

PMID- 9591788
TI  - Primary cutaneous Aspergillus ustus infection: second reported case.
AB  - We describe the second case of primary cutaneous Aspergillus ustus infection in
      an immunocompromised patient. Cutaneous aspergillosis was confirmed both by
      culture and positive fluorescent antibody staining. Few species of Aspergillus
      are pathogenic in human beings, and fewer still cause primary cutaneous disease.
      The only other reported case of aspergillosis from Aspergillus ustus occurred in
      an immunosuppressed patient who was temporally and geographically separated from
      ours.

PMID- 9591789
TI  - Kaposiform hemangioendothelioma: a locally aggressive vascular tumor.
AB  - Kaposiform hemangioendothelioma is a locally aggressive, endothelial-derived
      spindle cell neoplasm that occurs exclusively in infants and adolescents. Lesions
      are characterized by rapid growth and extension, and are often associated with
      Kasabach-Merritt syndrome and lymphangiomatosis. Clinically nonspecific, they can
      appear as tender rapidly expanding red plaques, nodules, grouped papules, or
      telangiectasias. The histology is distinctive, however, as it combines features
      of tufted angioma, progressive lymphangioma, and Kaposi's sarcoma in a
      characteristic pattern. We describe a patient with kaposiform
      hemangioendothelioma currently controlled with systemic prednisone.

PMID- 9591790
TI  - Follicular mucinosis as a presenting sign of acute myeloblastic leukemia.
AB  - Follicular mucinosis is often associated with mycosis fungoides and has been
      rarely observed to occur with other neoplastic and inflammatory conditions. We
      describe a 60-year-old patient with follicular mucinosis who later developed
      acute myelogenous leukemia. This is the first reported case of follicular
      mucinosis as a presenting sign of acute myeloblastic leukemia in the absence of
      mycosis fungoides or leukemia cutis.

PMID- 9591791
TI  - Carbamazepine-induced pseudolymphoma with CD-30 positive cells.
AB  - A 44-year-old woman known to be allergic to phenytoin was treated with
      carbamazepine for 1 month and developed fever, lymphadenopathy, pneumonitis,
      hepatitis, and a morbilliform eruption. A skin biopsy specimen showed atypical
      lymphocytes in the dermis that were CD-3+, CD-30+, and L26-. T-cell gene
      rearrangement studies were negative. A diagnosis of anticonvulsant
      hypersensitivity syndrome with histologic features of a pseudolymphoma was made
      and her illness quickly improved after carbamazepine was discontinued. This case
      was typical of the anticonvulsant hypersensitivity syndrome and demonstrated
      cross-reactivity among the aromatic anticonvulsants. However, to our knowledge,
      this represents the first report of a carbamazepine-induced hypersensitivity with
      histologic features of a cutaneous pseudolymphoma, including CD-30+ cells.

PMID- 9591792
TI  - Childhood-onset porphyria cutanea tarda: successful therapy with low-dose
      hydroxychloroquine (Plaquenil).
AB  - We describe a 4-year-old girl with a spontaneous blistering disorder that was
      consistent with porphyria cutanea tarda (PCT). There was no familial history of
      the disease or any obvious causative factors present. Oral hydroxychloroquine (3
      mg/kg) was given twice weekly along with vitamin E (200 U/d) as an antioxidant.
      Within 6 weeks, marked decreased blistering occurred and by 12 weeks no
      blistering was evident. Despite clinical improvement and tolerance of
      hydroxychloroquine, urinary uroporphyrin, aspartate aminotransferase, and
      ferritin levels continued to rise reaching peak levels at 16 weeks of therapy.
      Near total biochemical remission was observed at 40 weeks and all therapy was
      discontinued at 60 weeks.

PMID- 9591793
TI  - Melanoma of the soft parts (clear cell sarcoma): a case report and review of the
      literature.
AB  - Melanoma of the soft parts (clear cell sarcoma) is an uncommon soft tissue
      sarcoma that occurs in tendons and aponeuroses, usually of the lower extremity
      and is believed to be of neural crest origin. Although the exact histogenesis of
      this tumor is unknown and some controversy still exists, the generally accepted
      view is that it arises from neural crest cells that have the capability to
      produce melanin. Because melanin or melanosomes can be demonstrated in a majority
      of these cases, the term melanoma of the soft parts (MSP) has been advanced.
      These tumors commonly metastasize and have a very poor prognosis.

PMID- 9591794
TI  - Cutaneous lymphoplasmacytic lymphoma.
AB  - We report a case of cutaneous lymphoplasmacytic lymphoma with multiple
      recurrences. The patient's disease has been controlled with local radiotherapy,
      excision, and low dose chemotherapy. During the 9 years of his disease, he has
      not experienced extracutaneous involvement. This case demonstrates the indolent
      nature that may characterize cutaneous extramedullary plasmacytomas.

PMID- 9591795
TI  - Hereditary epidermolytic palmoplantar keratoderma (Vorner type) in a family with
      Ehlers-Danlos syndrome.
AB  - We describe a kindred in whom epidermolytic palmoplantar keratoderma occurred in
      association with Ehlers-Danlos syndrome type III (benign hypermobility syndrome).
      This kindred consisted of 27 members of four generations, 14 of whom had
      palmoplantar keratoderma (PPK). Of those who had palmoplantar keratoderma, 6 had
      Ehlers-Danlos type III (EDS II). The proband presented with diffuse, symmetrical
      hyperkeratotic plaques that were yellow and sharply demarcated, covering the
      entire palms and soles, in addition to marked large and small joint flexibility
      and skin hyperextensibility. A biopsy specimen from the palm revealed features of
      epidermolytic hyperkeratosis with acanthosis. To our knowledge, this is the first
      report of PPK in a family with Ehlers-Danlos syndrome. Linkage analysis of these
      two clinical traits showed that the genes responsible for PPK and EDS III are not
      closely linked, and therefore are not immediately adjacent. However, linkage at
      greater genetic distances could not be excluded.

PMID- 9591796
TI  - Lichen sclerosus following the lines of Blaschko.
AB  - A case of lichen sclerosus that developed in a pattern corresponding to the lines
      of Blaschko is described. This pattern of extragenital lichen sclerosus has not,
      to our knowledge, previously been reported and could result from an epidermal
      clone with altered androgen sensitivity supporting a hormonal pathogenesis for
      this disease.

PMID- 9591797
TI  - Inflammatory nevus comedonicus in children.
AB  - More than 100 years has passed since the first report of a nevus comedonicus. The
      earliest reports emphasized the inflammatory aspect of the nevus comedonicus as
      being the most significant problem. In the past 30 years, publications have
      ignored the inflammatory aspect of nevus comedonicus while emphasizing a variety
      of associated malformations. In this review, we describe five prepubertal
      children with prominent and persistent inflammatory changes limited to areas
      within a nevus comedonicus. In our experience, inflammation can be severe and
      resistant to treatment. Ultimately, surgical removal of the involved skin was
      required in two children.

PMID- 9591798
TI  - Cutaneous angiosarcoma of the face: clinicopathologic and immunohistochemical
      study of a case resembling rosacea clinically.
AB  - An unusual cutaneous angiosarcoma resembling rosacea clinically is described. A
      66-year-old man presented with a red discoloration and a diffuse swelling on his
      nose over a 2-year period that was diagnosed as rosacea. Despite antiinflammatory
      treatment, the infiltration increased and, after repeated skin biopsies, the
      diagnosis of a well-differentiated cutaneous angiosarcoma associated with a
      prominent inflammatory infiltrate was considered. The neoplasm was treated by
      surgery. The described case emphasizes that diffuse swelling and rosacea-like
      clinical features should be added to the variably clinical features of cutaneous
      angiosarcoma.

PMID- 9591799
TI  - Concomitant lichen scrofulosorum and erythema induratum.
AB  - We describe a patient in whom two tuberculids, lichen scrofulosorum, and erythema
      induratum occurred simultaneously. The clinical and histopathologic features were
      characteristic and a Mantoux test showed a positive reaction. There was no
      extracutaneous focus of tuberculosis. Polymerase chain reaction for mycobacteria
      in the skin lesions was negative, but her lesions responded rapidly to
      antituberculous chemotherapy.

PMID- 9591800
TI  - Bullous systemic lupus erythematosus: detection of antibodies against
      noncollagenous domain of type VII collagen.
AB  - A 9-year-old girl with systemic lupus erythematosus developed bullous eruption.
      Histopathologic examination showed subepidermal blistering and immunoglobulins
      (IgG, IgM, IgA) and complement components (C1q, C3) deposited linearly at the
      basement membrane zone. IgG in this patient's serum bound to the dermal side of 1
      mol/L sodium chloride-split normal human skin, and a 290 kd protein was
      identified in the dermal extract. The patient's serum recognized various epitopes
      on the noncollagenous domain as demonstrated by the use of fusion proteins of
      type VII collagen. Resolution of the bullous eruption occurred after treatment
      with dapsone.

PMID- 9591802
TI  - Degos disease in a patient with acquired immunodeficiency syndrome.
AB  - Malignant atrophic papulosis is a rare disorder characterized by pathognomonic
      cutaneous lesions that consist of infarctive thrombosis. Visceral involvement
      often occurs; the gastrointestinal tract and the central nervous system are most
      frequently involved. Malignant atrophic papulosis has not been previously
      described in an AIDS patient. We describe a 58-year-old homosexual man with AIDS
      who developed typical cutaneous lesions of malignant atrophic papulosis. No
      visceral involvement has been detected in 2 years.

PMID- 9591801
TI  - Follicular mucinosis presenting as an acneiform eruption: report of four cases.
AB  - Follicular mucinosis can be a primary idiopathic disease or a secondary disease
      associated with lymphoma. When it appears in childhood or adolescence, it is
      usually primary and self-limited. We describe four cases of follicular mucinosis
      occurring in early adulthood that have had protracted courses. Each presented as
      an unusual acneiform eruption. Two of the cases demonstrated a clonal genetic
      rearrangement of the T-cell receptor within the cutaneous lymphoid infiltrate, a
      finding not previously reported. Although its significance is not clear, the
      clonal lymphocytic expansion indicates a need for continued surveillance of these
      patients.

PMID- 9591803
TI  - Tufted hair folliculitis developing in a recalcitrant lesion of pemphigus
      vulgaris.
AB  - We describe tufted hair folliculitis that developed in a chronically erosive
      plaque on the scalp of a Japanese man patient with pemphigus vulgaris. After
      repeated intralesional corticosteroid injections, the erosive lesion improved,
      leaving multiple hairs emerging from single follicular openings. The current case
      suggests that localized exudative inflammatory lesions in the scalp regardless of
      cause can result in tufted hair formation.

PMID- 9591804
TI  - Use of topical cyclosporin in oral pemphigus.
AB  - The use of systemic cyclosporin in the treatment of pemphigus is well recognized.
      Oral lesions in pemphigus vulgaris are common but can be very difficult to treat.
      Short use of topical cyclosporin has been reported in a few cases of oral
      pemphigus. We report the successful use of topical cyclosporin for several years
      in a patient with debilitating oral pemphigus in whom systemic immunosuppressive
      agents and topical steroids had been ineffective and in whom cyclosporin was used
      not only to induce but also to maintain remission.

PMID- 9591805
TI  - Cutaneous malignant melanoma and oculodermal melanocytosis (nevus of Ota): report
      of a case and review of the literature.
AB  - A 29-year-old white man, with oculodermal melanocytosis, had a rapidly enlarging,
      erythematous, painful nodule over his left brow, within the nevus. The lesion was
      excised and diagnosed as a malignant melanoma. Systemic evaluation showed no
      evidence of distant disease. This is the tenth case reported of a cutaneous
      melanoma developing in a nevus of Ota. Melanoma arising in the choroid, brain,
      orbit, iris, ciliary body, or optic nerve in association with a nevus of Ota is
      well documented. Careful observation is necessary in patients with a nevus of
      Ota, particularly in white patients, in whom malignant degeneration seems to
      occur with a disproportionate frequency.

PMID- 9591806
TI  - Iatrogenic necrolytic migratory erythema: a case report and review of
      nonglucagonoma-associated necrolytic migratory erythema.
AB  - Necrolytic migratory erythema is characterized by waves of irregular erythema in
      which a central bulla develops, and subsequently erodes and becomes crusted. It
      usually occurs in patients with an alpha-islet cell tumor of the pancreas.
      However, necrolytic migratory erythema has also been observed in patients without
      an associated glucagonoma. We describe a woman with iatrogenic necrolytic
      migratory erythema. She received intravenous glucagon for hypoglycemia associated
      with an insulin-like growth factor II-secreting hemangiopericytoma. After
      chemotherapy, she developed necrolytic migratory erythema. The characteristics of
      the previously reported patients with nonglucagonoma-associated necrolytic
      migratory erythema are reviewed. In patients with nonglucagonoma-associated
      necrolytic migratory erythema, the dermatosis-related conditions most commonly
      observed were celiac disease or malabsorption, cirrhosis, malignancy, and
      pancreatitis; less common conditions included hepatitis, inflammatory bowel
      disease, heroin abuse, and odontogenic abscess. Although the pathogenesis of
      necrolytic migratory erythema remains unknown, hyperglucagonemia appears to have
      had a causative role in the development of this dermatosis in our patient.
      Patients who develop necrolytic migratory erythema should be evaluated for the
      presence of a glucagonoma; if a glucagonoma is ruled out, evaluation for other
      conditions known to occur with necrolytic migratory erythema, such as liver
      disease, malabsorptive disorders, and nonislet-cell tumors is warranted.

PMID- 9591807
TI  - Disseminated subcutaneous Nocardia farcinica abscesses in a nephrotic syndrome
      patient.
AB  - We describe an unusual case of disseminated subcutaneous abscesses caused by
      Nocardia farcinica in a 49-year-old man with nephrotic syndrome. He had received
      systemic corticosteroid therapy for 5 months. He developed a submandibular
      abscess associated with sialoadenitis on the right submaxillary gland. Magnetic
      resonance imaging revealed connection between the submandibular abscess and the
      right submaxillary gland. The subcutaneous abscess spread from the submandibular
      triangle to the left axillary region, the left upper arm, the left hypochondriac
      region, the left scapular region, the right epigastric region, and the bilateral
      legs. A chest radiograph and computed tomograms of the chest and the brain did
      not reveal any pathologic changes. The patient was successfully treated by
      surgical drainage of the abscesses and by oral administration of minocycline.

PMID- 9591808
TI  - Vitiligo.
AB  - The destruction of melanocytes is the cause of depigmented maculae that
      clinically represent the disease vitiligo. Although the cause is unknown, various
      theories such as the autoimmune, autocytotoxic, and neural hypotheses have been
      proposed. Extensive research has provided numerous answers regarding the
      pathogenesis, histopathologic evidence, and treatment of vitiligo. This
      discussion of vitiligo summarizes the varied clinical presentations of the
      disease, theories attempting to explain the mechanism of melanocyte destruction,
      histopathologic findings, and different treatment modalities currently available.

PMID- 9591809
TI  - An estimate of the annual direct cost of treating cutaneous melanoma.
AB  - BACKGROUND: Although the survival benefits of early stage melanoma have been
      clearly documented, the potential economic impact of early versus late stage
      disease has not been assessed. OBJECTIVE: Our purpose was to estimate the annual
      direct cost of diagnosing and treating melanoma, based on the number of projected
      cases of melanoma entering each stage in 1997. METHODS: A model was constructed
      with assumptions derived from the literature and clinical experience at the
      Massachusetts General Hospital Melanoma Center and the Boston University Medical
      Center. Cost estimates were based on 1997 Boston area Medicare reimbursements.
      RESULTS: The annual direct cost of treating newly diagnosed melanoma in 1997 was
      estimated to be $563 million. Stage I and II disease each comprised about 5% of
      the total cost; stage III and stage IV disease consumed 34% and 55% of the total
      cost, respectively. About 90% of the total annual direct cost of treating
      melanoma in 1997 was attributable to less than 20% of patients (those patients
      with advanced disease, that is, stage III and stage IV). CONCLUSION: In addition
      to the potential survival advantages, aggressive primary prevention through sun
      protection and intensive screening to enhance earlier detection should reduce the
      economic burden of melanoma care.

PMID- 9591811
TI  - Narrow band UVB (311 nm) phototherapy and PUVA photochemotherapy: a combination.
AB  - BACKGROUND: Psoralen-UVA (PUVA) photochemotherapy is widely used for the
      treatment of psoriasis despite concerns of skin carcinogenesis from high
      cumulative UVA doses and number of treatments. OBJECTIVE: We attempted to
      determine whether combined bath-PUVA with narrow-band (311 nm) phototherapy
      improves efficacy and reduces long-term toxicity. METHODS: Twelve psoriatic
      patients underwent phototesting with 311 nm lamps and, after topical bath-water
      psoralen sensitization, with 311 nm, UVA, or both radiations. Patients were
      treated with bath-PUVA on one side of the body and with bath-PUVA plus 311 nm
      exposures (bath-PUVA-311 nm) on the other side. On both sides, four weekly
      treatments were delivered and UVA doses were increased once weekly whereas 311 nm
      doses were adjusted at each exposure. RESULTS: Psoralen sensitization did not
      modify the erythematous threshold to 311 nm radiation. However, 311 nm exposures
      enhanced the phototoxic activity of bath-PUVA. Bath-PUVA-311 nm cleared psoriasis
      with fewer exposures and lower cumulative UVA doses under the same minimally
      erythemogenic conditions. CONCLUSION: Combination with 311 nm exposures enhanced
      the phototoxic and therapeutic activities of bath-PUVA.

PMID- 9591810
TI  - Clinical and histologic trends of melanoma.
AB  - BACKGROUND: Several changing clinical and histopathologic melanoma trends
      occurred from the 1950s to the 1980s. OBJECTIVE: The purpose of this study was to
      evaluate melanoma trends during the past decade and to compare present trends to
      those documented during the past four decades. METHODS: Sex, age at diagnosis,
      location, tumor thickness, stage, and histologic subtypes were evaluated from
      1984 to 1995 and compared with trends during the past four decades. RESULTS: Most
      changing trends from the past four decades have slowed or stabilized during the
      past decade. CONCLUSION: Complete reporting of all melanomas to central tumor
      registries is necessary to accurately analyze present and future melanoma trends.
      Ongoing and new prevention and control strategies beginning at birth may be
      necessary to continue the positive efforts to curtail the melanoma epidemic.

PMID- 9591812
TI  - Contact hypersensitivity to tixocortol pivalate.
AB  - BACKGROUND: Tixocortol pivalate is an established marker to topical
      corticosteroid allergy. The prevalence of tixocortol pivalate hypersensitivity is
      well established in Europe, where exposure to this corticosteroid as a
      therapeutic agent varies. In the United States, tixocortol pivalate is not
      commercially available and the prevalence of hypersensitivity to it is unknown.
      OBJECTIVE: We investigated the prevalence of tixocortol pivalate hypersensitivity
      in our patch-tested population. We further characterized these patients by
      clinical background, other contact allergens, and the reactivity to other
      corticosteroids. METHODS: Tixocortol pivalate has been incorporated in our
      standard 1-52 patch test series since November 1992. We reviewed the histories
      and patch test results in all patients tested with the standard 1-52 series from
      November 1992 to December 1996. RESULTS: Of 1536 patch-tested patients, 45 had
      hypersensitivity to tixocortol pivalate. Dermatitis involving the face was the
      most common (14 patients). Of the 45 patients, 40 had another allergen identified
      on patch testing. Eighteen patients underwent further patch testing to an
      extended corticosteroid panel, and 14 had sensitivity to another steroid agent.
      CONCLUSION: The 2.9% prevalence of tixocortol pivalate hypersensitivity in our
      patch test population is within the range reported in Europe. Patients with
      tixocortol pivalate hypersensitivity tend to have other contact allergens on
      patch testing. Predisposing factors to tixocortol pivalate hypersensitivity
      include facial dermatitis and sensitivity to other contact allergens.

PMID- 9591813
TI  - Mycosis fungoides in young patients: clinical characteristics and outcome.
AB  - BACKGROUND: Mycosis fungoides (MF) can begin as early as the first decade of
      life. Few studies have reviewed MF in younger patients and none has been large
      enough to assess prognosis and outcome. OBJECTIVE: We reviewed the clinical
      characteristics, prognosis, factors related to disease progression, and therapy
      in patients with MF younger than 35 years of age. METHODS: Fifty-eight patients
      were entered into this retrospective cohort analysis. RESULTS: Significantly
      fewer patients with MF who are younger than 35 years presented with erythroderma
      (T4) and more with limited patch/plaque (T1) disease than older patients.
      Duration of skin disease before diagnosis of MF did not vary between the two
      groups. The long-term survival of younger patients with MF is significantly
      decreased when compared with a race-, age-, and sex-matched control population (p
      < 0.001). Disease-specific survivals (DSS) of younger and older patients are
      similar, but young patients show a slight but significantly better overall DSS (p
      < 0.02). However, DSS comparison of generalized patch/plaque (T2) and tumor stage
      (T3) patients with MF showed no significant difference between young and old
      patients (p=0.47, p=0.59). Patient age was not a significant predictor of
      survival when controlled for T-stage. Sixteen of 58 young patients with MF have
      died, 13 because of MF (22%), compared with 138 of 500 older patients (28%) who
      died as a result of MF. All younger patients with MF who progressed had at least
      T2 disease at presentation. Fifty of 56 young patients with MF and T1-T3 disease
      were treated initially with total skin electron beam or topical nitrogen mustard.
      The response to therapy was similar in younger and older patients with MF.
      CONCLUSION: T1 disease is more common and T4 disease is unusual in young patients
      with MF compared with an older population of patients with MF. Young patients
      with T1 disease, all of whom were treated with either topical nitrogen mustard or
      total skin electron beam therapy, or both therapies, showed no disease
      progression. Overall, young patients with MF showed slightly better DSS, but this
      was because of differences in stage distribution.

PMID- 9591814
TI  - Effect of onychomycosis on quality of life.
AB  - BACKGROUND: Onychomycosis impairs normal nail functions, causes considerable
      pain, interferes with daily activities, and has negative psychosocial effects.
      OBJECTIVE: Our purpose was to determine patients' perception of onychomycosis on
      the quality of life. METHODS: A total of 258 patients with confirmed
      onychomycosis were surveyed by telephone at three centers. Responses to a
      standardized quality-of-life questionnaire were analyzed for patient
      demographics, physical and functional impact, psychosocial impact, and economic
      impact. RESULTS: Highest positive responses were nail-trimming problems (76%),
      embarrassment (74%), pain (48%), nail pressure (40%), and discomfort wearing
      shoes (38%). Ability to pick up small objects was impaired in 41% of subjects
      with fingernail involvement. More than 58 onychomycosis-related sick days and 468
      medical visits (1.8 per subject) were reported during a 6-month period.
      CONCLUSION: Onychomycosis has significant social, psychologic, health, and
      occupational effects. Relevance of quality-of-life issues to overall health,
      earning potential, and social functioning should prompt reconsideration of the
      value of aggressive treatment of and financial coverage for onychomycosis.

PMID- 9591815
TI  - Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment
      of plaque psoriasis.
AB  - BACKGROUND: A new class of topical receptor-selective acetylenic retinoids, the
      first of which is tazarotene, has been developed. OBJECTIVE: Our purpose was to
      compare the safety, efficacy, and duration of therapeutic effect of 12 weeks of
      once-daily tazarotene 0.1% and 0.05% gel with that of twice-daily fluocinonide
      0.05% cream in the treatment of patients with plaque psoriasis. METHODS: Three
      hundred forty-eight patients with plaque psoriasis were enrolled and 275 patients
      completed a multicenter, investigator-masked, randomized, parallel-group clinical
      trial. RESULTS: Both tazarotene gels were as effective as fluocinonide in
      reducing plaque elevation after 1 week of treatment, and tazarotene 0.1% gel was
      similar to fluocinonide in reducing scaling of trunk/limb lesions at all study
      weeks except week 4. Tazarotene 0. 1% gel was similar to fluocinonide in reducing
      scaling of knee/elbow lesions at weeks 8 and 12. Fluocinonide had a significantly
      greater effect on erythema than tazarotene at weeks 2 through 8. However,
      treatments were not significantly different at week 12, and tazarotene
      demonstrated significantly better maintenance of therapeutic effect after
      cessation of therapy. CONCLUSION: Tazarotene 0.1% and 0.05% gels were safe and
      effective in the treatment of mild-to-moderate plaque psoriasis.

PMID- 9591816
TI  - Intrauterine epidermal necrosis: report of three cases.
AB  - BACKGROUND: Extensive epidermal necrosis in newborn infants is an unusual event
      of heterogeneous cause. OBJECTIVE: The objective of this article is to describe
      what seems to be a previously unrecognized lethal disease. METHODS: The clinical
      and histopathologic features of three premature infants, two of them nonidentical
      twins, and the autopsy findings of one of them were analyzed. RESULTS:
      Intrauterine lethal epidermal necrosis with hair follicle calcification, except
      for the face, hands, feet, elbows, and knees, was present in all three patients.
      Some histopathologic features were suggestive of epidermal apoptosis. CONCLUSION:
      We propose that the clinicopathologic alterations in our patients represent a new
      condition that may be caused by massive epidermal apoptosis.

PMID- 9591817
TI  - Ocular melanomas and melanocytic lesions of the eye.
AB  - This article describes several melanocytic lesions of the eye. Benign and
      malignant lesions will be discussed as well as a review of the dysplastic nevus
      syndrome and its proposed association with ocular melanoma. Ocular melanomas
      arise from the same embryologically derived melanocytes as their cutaneous
      counterparts. However, ocular and cutaneous melanomas differ in many respects.
      The diagnosis and management of these ocular tumors rely heavily on the
      ophthalmologist. However, knowledge of melanocytic lesions will aid the
      dermatologist in detection and in proper referral of these patients.

PMID- 9591818
TI  - Advances in melanoma therapy.
AB  - This review discusses several advances in melanoma therapy that have recently
      occurred or are presently in a developmental stage. We discuss the history and
      present dogma regarding assessment of the regional lymph nodes and adjuvant
      therapy for melanoma. Of special interest is radiolymphatic sentinel node mapping
      of the lymph nodes and adjuvant interferon alfa-2b for thick primary lesions and
      stage III disease. We also discuss several evolving novel and innovative genetic
      immunotherapy approaches for patients with stage IV disease.

PMID- 9591819
TI  - The multidisciplinary melanoma clinic: a cost outcomes analysis of specialty
      care.
AB  - The traditional process of melanoma care delivery can differ substantially among
      providers regarding screening laboratories, staging work-ups, surgical margins,
      and outpatient versus inpatient surgical management. It has been suggested that
      multidisciplinary care may provide a more cost-effective management approach. We
      sought to evaluate whether coordinated multidisciplinary melanoma care that
      follows evidence-based, consensus-approved clinical practice guidelines at a
      large academic medical center can provide a more efficient alternative to
      traditional community-based strategies with clinical outcomes that are at least
      equivalent. The University of Michigan Multidisciplinary Melanoma Clinic (MDMC)
      possesses a database of demographic, clinical, and treatment information for all
      patients seen since its inception. A consecutive sample of 104 patients with
      local disease who were treated in the Michigan community were compared with 104
      blindly selected subjects treated at the MDMC during an identical time period,
      matched for Breslow depth and melanoma body site. Patients treated in the MDMC
      would save a third party payer roughly $1600 per patient when compared with a
      similar group treated in the Michigan community. Surgical morbidity, length of
      hospitalization, and long-term survival of MDMC patients were similar to those
      reported in the literature. The cost discrepancy is explained by the fundamental
      differences in the usage pattern of health care resources exhibited by the MDMC
      compared with the community setting.

PMID- 9591820
TI  - What promotes skin self-examination?
AB  - The American Academy of Dermatology's national program of Melanoma/Skin Cancer
      Detection and Prevention, developed in response to the rising incidence of
      invasive melanoma in the United States, has annually produced extensive print,
      radio, and television coverage about performing skin self-examination (SSE). This
      study was conducted to determine factors that motivate people to perform SSE. A
      1996 telephone survey evaluated performance of SSE for skin cancer and used
      questions to identify self-perceived. The performance of SSE was directly
      correlated with the self-perceived risk of the development of melanoma or skin
      cancer and discussions with physicians or nurses. People were motivated to
      perform SSE based on their perceived risk and discussions with doctors. Because
      patients most easily have access to primary care physicians, these physicians
      must be educated to identify those who are at risk for the development of
      melanoma. Primary care physicians and nurses should be encouraged to counsel
      patients about risk levels, the utility of SSE in limiting their risk, and how to
      perform SSE. To facilitate this process, risk levels for the development of
      melanoma (defined on the basis of simple and readily ascertained characteristics
      that help to educate physicians, nurses, and patients) are provided.

PMID- 9591821
TI  - Surgical pearl: the "unsuture" technique for skin grafts.

PMID- 9591822
TI  - Worsening of lichen myxedematosus during interferon alfa-2a therapy for chronic
      active hepatitis C.

PMID- 9591823
TI  - Herpes zoster after varicella immunization.

PMID- 9591824
TI  - Lasting immunity to varicella in doctors study (L.I.V.I.D. study).

PMID- 9591825
TI  - Severe neutropenia associated with oral terbinafine therapy.

PMID- 9591826
TI  - Multiple basal cell carcinomas of the limb after adjuvant treatment of melanoma
      with isolated limb perfusion.

PMID- 9591827
TI  - Spontaneous clearing of psoriasis after stroke.

PMID- 9591828
TI  - Lichen planus associated with Becker's nevus.

PMID- 9591829
TI  - Chevron nail.

PMID- 9591830
TI  - Executive summary of the national "Sun Safety: Protecting Our Future" Conference:
      American Academy of Dermatology and Centers for Disease Control and Prevention.
      New York, New York, May 1 and 2, 1997.

PMID- 9591831
TI  - Penile lentiginosis.

PMID- 9591832
TI  - Hydroxyurea-induced dermopathy: a unique lichenoid eruption complicating long
      term therapy with hydroxyurea.

PMID- 9591833
TI  - Melanoma and levodopa.

PMID- 9591834
TI  - Antimicrobial agents for the dermatologist. I. Beta-lactam antibiotics and
      related compounds.

PMID- 9591835
TI  - Cutaneous nodular reaction to oral mercury.

PMID- 9591836
TI  - Phenytoin-like hypersensitivity associated with lamotrigine.

PMID- 9591837
TI  - Immunohistochemical characterization of dermatofibrosarcoma protuberans with
      practical applications for diagnosis and treatment.

PMID- 9591838
TI  - Apolipoprotein E and the CNS response to injury.
AB  - Apolipoprotein E (apoE) is a multifunctional protein with an expanding role in
      the neurobiology of disease. Although originally described in the context of
      cholesterol metabolism, interest in the neurobiology of apoE has intensified
      following the association between apoE genotype and risk of developing
      Alzheimer's disease. Recent clinical observations also suggest that apoE genotype
      may influence recovery after a variety of neurological insults. Thus, in addition
      to the study of disease-specific mechanisms by which apoE may modulate
      susceptibility of developing Alzheimer's disease, there has been an increasing
      focus on its role in modulating the CNS response to acute injury. Although the
      neurobiology of apoE in the injured brain remains incompletely defined, there is
      evidence to suggest neurotrophic, immunomodulatory, and antioxidant effects.

PMID- 9591839
TI  - Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal
      neurons via adenosine receptor.
AB  - The effect of propentofylline, an adenosine uptake inhibitor, on ischemic
      tolerance was investigated in the gerbil global ischemia model. Propentofylline
      was administered 24 hours after short preconditioning ischemia, and animals were
      subjected to 5-minute ischemia 24 hours thereafter. Propentofylline at a dose of
      20 mg/kg intraperitoneally, but not at a dose of 10 mg/kg, significantly
      potentiated the protective effect of preconditioning ischemia in the CA1
      hippocampal neurons. This effect was completely abolished by simultaneous
      administration of theophylline (20 mg/kg), an adenosine receptor blocker. This
      finding suggests the involvement of adenosine receptor for the development of
      ischemic tolerance.

PMID- 9591840
TI  - Effects of damage to the basal forebrain on brain glucose utilization: a
      reevaluation using positron emission tomography in baboons with extensive
      unilateral excitotoxic lesion.
AB  - Neuronal loss in the basal forebrain cholinergic structures and frontotemporal
      hypometabolism are two characteristics of Alzheimer's disease, but their
      interrelations still are unsettled. We previously reported that unilateral
      electrolytic lesions of the nucleus basalis of Meynert in baboons were associated
      with marked but transient cortical hypometabolism. The current study reevaluates
      this issue using improved methodology. Baboons with unilateral ibotenic acid
      lesion of all three basal forebrain cholinergic structures (IBO group) were
      compared with sham-operated animals. The CMRglc was measured with high-resolution
      coronal positron emission tomography scanning coregistered with magnetic
      resonance imaging, before surgery and serially between 4 and 72 days afterward.
      Severe histologic basal forebrain damage and a decrease of more than 50% in
      cortical choline acetyltransferase activity were found postmortem in the IBO
      group. Transient and nonspecific hypometabolism was found in the needle track
      area in both groups. Compared with the sham-operated group, only marginally
      significant decreases in ipsilateral-contralateral CMRglc ratios were observed in
      the IBO group, affecting only 1 of 14 neocortical areas investigated (the
      anterior temporal cortex) at a single postsurgical time (day 14), and the
      posterior hippocampal region at days 14 and 38. Furthermore, there was no
      consistently significant correlation between ipsilateral-contralateral CMRglc
      ratios and cortical choline acetyltransferase activity values in any of the four
      regions analyzed. These results suggest that cholinergic deafferentation play at
      best a marginal role in the brain hypometabolism observed in Alzheimer's disease.

PMID- 9591841
TI  - [3H]DOPA formed from [3H]tyrosine in living rat brain is not committed to
      dopamine synthesis.
AB  - Tyrosine hydroxylase of catecholamine neurons catalyzes the synthesis of 3,4
      dihydroxphenylalanine (DOPA), which is subsequently metabolized to dopamine by
      DOPA decarboxylase (DDC). However, DOPA is not committed to decarboxylation in
      vivo because export of DOPA from brain and metabolism of DOPA other than
      decarboxylation are possible. To estimate the relative magnitudes of the several
      fates of DOPA, the kinetics of the uptake and metabolism of L-[3H]tyrosine
      ([3H]Tyr, intravenous infusion) was measured in brain of rats pretreated with NSD
      1015, an inhibitor of DDC. Some rats were pretreated with haloperidol before the
      blockade of DDC. The [3H]Tyr was incorporated into brain protein at a rate
      constant of 0.03 min(-1). The relative tyrosine hydroxylase activity in striatum
      was 0.005 min(-1) at 30 minutes after NSD 1015, 0.011 min(-1) 3 hours later, and
      0.020 min(-1) after haloperidol treatment. The rate constant for the clearance of
      DOPA from brain (0.06 min(-1)) and earlier estimates of the rate constant of DDC
      activity in striatum (0.26 min(-1)) together predict that 80% of DOPA formed in
      normal rat striatum normally is available for dopamine synthesis. It follows that
      modulation of DDC activity can influence the rate of DA synthesis by affecting
      the relative magnitude of the several fates of DOPA in living brain.

PMID- 9591842
TI  - "Facilitated" amino acid transport is upregulated in brain tumors.
AB  - The goal of this study was to determine the magnitude of "facilitated" amino acid
      transport across tumor and brain capillaries and to evaluate whether amino acid
      transporter expression is "upregulated" in tumor vessels compared to capillaries
      in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non
      metabolized [14C]-labeled amino acid, and a reference molecule for passive
      vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga
      DTPA), were used in these studies. Two experimental rat gliomas were studied (C6
      and RG2). Brain tissue was rapidly processed for double label quantitative
      autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA.
      Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA,
      microL/min/g) produced from the autoradiograms and the histology were obtained
      from the same tissue section. These three images were registered in an image
      array processor; regions of interest in tumor and contralateral brain were
      defined on morphologic criteria (histology) and were transferred to the
      autoradiographic images to obtain mean values. The facilitated component of ACPC
      transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and
      paired comparisons between tumor and contralateral brain were performed. ACPC
      flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was
      >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this
      difference was largely (approximately 90%) due to facilitated ACPC transport.
      Substantially higher K1ACPC values compared to corresponding K1DTPA values were
      also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were
      more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values
      for RG2 gliomas was not significantly higher than that of contralateral cortex,
      although a approximately 2-fold difference in facilitated transport is obtained
      after normalization for differences in capillary surface area between RG2 tumors
      and contralateral cortex. K1ACPC, deltaK1ACPC, and K DTPA were directly related
      to tumor cell density, were higher in regions of "impending" necrosis, and the
      tumor/contralateral brain ACPC radio-activity ratios (0 to 10 minutes) were very
      similar to that obtained with 0 to 60 minutes experiments. These results indicate
      that facilitated transport of ACPC is upregulated across C6 and RG2 glioma
      capillaries, and that tumors can induce upregulation of amino acid transporter
      expression in their supporting vasculature. They also suggest that early imaging
      (e.g., 0 to 20 minutes) with radiolabeled amino acids in a clinical setting may
      be optimal for defining brain tumors.

PMID- 9591843
TI  - Characterization of angiogenesis and microcirculation of high-grade glioma: an
      intravital multifluorescence microscopic approach in the athymic nude mouse.
AB  - The current study follows angiogenesis and microcirculatory changes associated
      with malignant glioma growth by means of an intravital fluorescence microscopic
      approach, which allows for the direct and continuous visualization of the glioma
      microvasculature and its quantitative analysis. Fluorescently labeled C6 rat
      glioma cells (5 x 10(5)) were implanted into dorsal skinfold chamber preparations
      of athymic nude mice. Glioma growth, vascularization, microhemodynamics, vascular
      permeability, and leukocyte-endothelial cell interactions were simultaneously
      followed over a 22-day observation period using intravital epiillumination
      microscopy and a multifluorescent labeling technique. Analysis of the process of
      glioma vascularization revealed three stages with distinct microvascular
      characteristics: avascular stage (days 0 to 6), lag of glioma growth but initial
      glioma-induced angiogenesis within the host tissue in peritumoral areas; early
      vascular stage (days 6 to 14), glioma cell proliferation associated with a
      spatially homogeneous development of a glioma microvasculature; and late vascular
      stage (days 14 to 22), exponential tumor growth and expansion (> 400 mm3) with
      high vascular densities in the peritumoral region and reduced vascularization
      (microvascular perfusion) in the glioma center. Within the center, the functional
      vessel length per area correlated inversely with glioma size (P < 0.01). In the
      peritumoral region, functional vessel length per area was independent of glioma
      size, indicating persistent, high angiogenic activity throughout the observation
      period. Thus, the microvasculature of mature gliomas revealed a microvascular
      zonal division with a progressive reduction of the functional vessel length per
      area within the tumor center. The perfusion failure of individual microvessels
      within the glioma center was partly compensated by an increase of diameters (P <
      0.05), and thus by an increase of blood flow in these functional microvessels (P
      < 0.05) over time. Histologic analysis demonstrated both expanding and
      infiltrating growth patterns, as well as focal necroses on day 22. These are the
      first data from repeated in vivo analysis of glioma growth, vascularization, and
      microcirculation.

PMID- 9591844
TI  - Oligodendrocytes and microglia are selectively vulnerable to combined hypoxia and
      hypoglycemia injury in vitro.
AB  - The major classes of glial cells, namely astrocytes, oligodendrocytes, and
      microglial cells were compared in parallel for their susceptibility to damage
      after combined hypoxia and hypoglycemia or hypoxia alone. The three glial cell
      types were isolated from neonatal rat brains, separated, and incubated in N2/CO2
      gassed buffer-containing glucose or glucose substitutes, 2-deoxyglucose or
      mannitol (both nonmetabolizable sugars). The damage to the cells after 6 hours'
      exposure was determined at 0, 1, 3, 7 days based on release of lactate
      dehydrogenase and counting of ethidium bromide-stained dead cells, double-stained
      with cell-type specific markers. When 2-deoxyglucose replaced glucose during 6
      hours of hypoxia, both oligodendrocytes and microglia rarely survived (18% and
      12%, respectively). Astroglia initially increased the release of lactate
      dehydrogenase but maintained 98% to 99% viability. When mannitol, a radical
      scavenger and osmolarity stabilizer, replaced glucose during 6 hours of hypoxia,
      oligodendrocytes rarely survived (10%), astroglia survival remained at 99%, but
      microglia survival increased to 50%. After exposure to 6 and 42 hours,
      respectively, of hypoxic conditions alone, oligodendrocytes exhibited 10%
      survival whereas microglia and astroglia were only temporarily stressed and
      subsequently survived. In conclusion, oligodendrocytes, then microglia, are the
      most vulnerable glial cell types in response to hypoxia or hypoglycemia
      conditions, whereas astrocytes from the same preparations recover.

PMID- 9591845
TI  - Role of endothelial nitric oxide synthase in hypoxia-induced pial artery
      dilation.
AB  - Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least
      in part, through the formation of cGMP and the subsequent release of methionine
      enkephalin and leucine enkephalin in the newborn pig. In separate studies, these
      opioids also were observed to elicit NO-dependent pial artery dilation, whereas
      light/dye endothelial injury reduced hypoxic pial dilation. The current study was
      designed to investigate the role of the endothelial isoform of NO synthase in
      hypoxic pial dilation, associated opioid release, and opioid dilation in piglets
      equipped with a closed cranial window. N-iminoethyl-L-ornithine (L-NIO) (10(-6)
      mol/L), an antagonist that may have greater endothelial NO synthase inhibitory
      selectivity, had no effect on dilation elicited by hypoxia (PO2 approximately 35
      mm Hg) (24 +/- 2 versus 24 +/- 2% in the absence and presence of L-NIO,
      respectively, n = 8). Hypoxic dilation was accompanied by increased CSF cGMP,
      which also was unchanged in the presence of L-NIO (394 +/- 19 and 776 +/- 63
      versus 323 +/- 13 and 739 +/- 25 fmol/mL for control and hypoxia in the absence
      and presence of L-NIO, respectively, n = 6). Additionally, hypoxic pial dilation
      was associated with increased CSF methionine enkephalin, which also was unchanged
      in the presence of L-NIO (992 +/- 73 and 2469 +/- 197 versus 984 +/- 18 and 2275
      +/- 185 pg/mL, respectively, n = 6). In contrast, methionine enkephalin-induced
      dilation was blocked by L-NIO (6 +/- 1, 10 +/- 1, and 16 +/- 1 versus 1 +/- 1, 1
      +/- 1, and 2 +/- 1% for 10(-10), 10(-8), 10(-6) mol/L methionine enkephalin,
      respectively, before and after L-NIO, n = 8). Substance P-induced pial dilation
      was blunted by L-NIO, whereas responses to sodium nitroprusside and N-methyl-D
      aspartate were unchanged. These data indicate that endothelial NO synthase
      contributes to opioid-induced pial artery dilation but not hypoxia-induced
      dilation. Additionally, these data suggest that neuronally derived NO contributes
      to hypoxic pial dilation.

PMID- 9591846
TI  - Neuroprotective efficacy and mechanisms of novel pyrrolopyrimidine lipid
      peroxidation inhibitors in the gerbil forebrain ischemia model.
AB  - A brief period of bilateral carotid occlusion (BCO)-induced forebrain ischemia in
      gerbils triggers neuronal degeneration and the subsequent expression of amyloid
      precursor protein (APP), b-amyloid protein (b-AP), and apolipoprotein E (APO-E)
      in the selectively vulnerable CA1 region of the hippocampus. The increase in
      immunoreactivity is secondary to the postischemic degeneration of the CA1 neurons
      and is largely astrocyte-derived as evidenced by a simultaneous increase in glial
      fibrillary acidic protein (GFAP) staining. Oxygen radical-induced lipid
      peroxidation has been strongly suggested to play a role in postischemic neuronal
      damage and Alzheimer's disease. Recent literature suggests a possible link
      between early oxidative stress and APP overexpression. Therefore, the present
      investigation examined the effect of two novel brain-penetrating
      pyrrolopyrimidine lipid peroxidation inhibitors (PNU-101033E and PNU-104067F) on
      CA1 neurodegeneration and the subsequent increase in APP, b-AP, APO-E, and GFAP
      immunostaining at 4 days after a 5-minute episode of forebrain ischemia. Using an
      antibody for lipid peroxidation-derived malondialdehyde (MDA)-modified proteins,
      the authors also examined the effects of PNU-104067F on MDA immunostaining 2 days
      after ischemia, before completion of the neuronal loss. At 2 days, the authors
      also evaluated microglial activation using an antibody to surface major
      histocompatibility complex class II antigen expressed by activated microglia.
      Gerbils were treated at 30 mg/kg orally 30 minutes before the BCO and 2 hours
      after ischemia, followed by daily dosing for the next day (microglia and MDA) and
      the successive 3 days for APP, b-AP, APO-E, and GFAP immunostaining. APP and APO
      E staining was significantly suppressed by 50% and 66%, respectively, with either
      compound. b-AP immunoreactivity was decreased 56% with both compounds, and GFAP
      expression was significantly decreased 53% (PNU-101033E) and 60.5% (PNU-104067F).
      There was a concomitant partial sparing of the CA1 hippocampal neurons by both
      PNU-101033E and PNU-104067F (P < .01) as determined by cresyl violet
      histochemistry. PNU-104067F significantly inhibited lipid peroxidation-derived
      MDA immunostaining and microglia activation (P < .05) at 48 hours after ischemia.
      Brain-penetrable lipid peroxidation inhibitors may provide attenuation of various
      glial response proteins after ischemic injury, probably secondary to neuronal
      protection.

PMID- 9591847
TI  - Long-term neuroprotection by benzodiazepine full versus partial agonists after
      transient cerebral ischemia in the gerbil [corrected].
AB  - The ability of diazepam, a benzodiazepine full agonist, and imidazenil, a
      benzodiazepine partial agonist, to protect hippocampal area CA1 neurons from
      death for at least 35 days after cerebral ischemia was investigated. Diazepam (10
      mg/kg) administered to gerbils 30 and 90 minutes after forebrain ischemia
      produced significant protection of hippocampal area CA1 pyramidal neurons 7 days
      later. In gerbils surviving for 35 days, diazepam produced the same degree of
      neuroprotection (70% +/- 30%) in the hippocampus compared with 7 days after
      ischemia. The therapeutic window for diazepam was short; there was no significant
      neuroprotection when the administration of diazepam was delayed to 4 hours after
      ischemia. The neuroprotective dose of diazepam also produced hypothermia
      (approximately 32 degrees C) for several hours after injection. To assess the
      role of hypothermia in neuroprotection by diazepam, hypothermia depth and
      duration was simulated using a cold-water spray in separate gerbils. Seven days
      after ischemia, neuroprotection by hypothermia was similar to that produced by
      diazepam. However, 35 days after ischemia, there was no significant protection by
      hypothermia, suggesting that hypothermia does not play a significant role in long
      term diazepam neuroprotection. Imidazenil (3 mg/kg), which produced only minimal
      hypothermia, protected area CA1 of hippocampus to the same degree as that by
      diazepam 7 days after ischemia. At 35 days after ischemia, significant protection
      remained, but it was considerably reduced compared with 7 days. Like diazepam,
      the therapeutic window for imidazenil was short. Imidazenil neuroprotection was
      lost when the drug was administered as early as 2 hours after ischemia. The
      ability of ischemia to produce deficits in working memory and of benzodiazepines
      to prevent the deficits also was investigated. Gerbils trained on an eight-arm
      radial maze before ischemia demonstrated a significant increase in the number of
      working errors 1 month after ischemia. The ischemia-induced deficits in working
      memory were completely prevented by diazepam but not by imidazenil. There was a
      significant, but weak, negative correlation between the degree of CA1 pyramidal
      cell survival and the number of working errors in both the diazepam and
      imidazenil groups. Thus, if given early enough during reperfusion, both
      benzodiazepine full and partial agonists are neuroprotective for at least 35
      days, but the lack of sedating side effects of imidazenil must be weighed against
      its reduced efficacy.

PMID- 9591848
TI  - Induction of heme oxygenase protein protects neurons in cortex and striatum, but
      not in hippocampus, against transient forebrain ischemia.
AB  - To clarify whether heme oxygenase-1 (HO-1) protein plays a protective role
      against cerebral ischemia, we investigated the effects of an HO inhibitor (tin
      mesoporphyrin IX [SnMP] three doses of 30 micromol/kg, intraperitoneally) and an
      HO inducer (hemin, three doses of 30 micromol/kg, intraperitoneally) on the
      pathologic outcome and on the immunohistochemical reaction for HO-1 after 20
      minute transient forebrain ischemia followed by 3-day reperfusion in rats. Hemin
      significantly increased viable neurons in the cortex (compared to the SnMP
      treated group, P < .05) and striatum (compared to the saline-treated group at P <
      .01 and SnMP-treated group at P < .05), and intense HO-1 immunoreactivity was
      observed in cortex and striatum, whereas the administration of SnMP tended to
      decrease viable neurons in the parietal cortex. In contrast, neither hemin nor
      SnMP affected the pathologic outcome in the CA1 and CA3 hippocampi, in which HO-1
      immunoreactivity was weak. These results suggest that induction of HO-1 protein
      may contribute to cellular defense against ischemic damage in brain regions where
      potential ability to synthesize HO-1 is retained in ischemia.

PMID- 9591850
TI  - Role of adenosine in cerebral vasodilator responses to sciatic nerve stimulation.

PMID- 9591849
TI  - Cerebral ischemia after bilateral carotid artery occlusion and intraluminal
      suture occlusion in mice: evaluation of the patency of the posterior
      communicating artery.
AB  - Cerebral ischemia models using mice have drawn increasing attention, particularly
      because of the availability of transgenic animals. However, the variability of
      intracranial vasculature at the circle of Willis in mice can influence the degree
      of ischemia in both the bilateral common carotid artery (CCA) occlusion and
      intraluminal suture occlusion models. We have developed a method to predict the
      extent of the anastomosis between carotid and vertebrobasilar circulation in
      three mouse strains (C57BL/6, CBA, and DBA/2) by measuring cortical
      microperfusion with laser Doppler flowmetry during a 1-minute occlusion of both
      CCA. When animals showed residual cortical microperfusion of less than 12% during
      bilateral CCA occlusion, the mice showed absence of functional anastomosis,
      developed ATP depletion in the frontal cortex during occlusion, and had ischemic
      neuronal death in the hippocampus and caudoputamen after occlusion for 15 minutes
      and recirculation for 7 days. Furthermore, those mice exhibited decreased local
      cerebral blood flow and associated ischemic neuronal death in the hippocampus,
      within the territory supplied by the posterior cerebral artery, with the
      intraluminal suture occlusion model. The current study demonstrates the need for
      assessment of intracranial vasculature in each animal by measuring cortical
      microperfusion during temporary occlusion of both CCA, no matter whether cerebral
      ischemia is produced by bilateral CCA occlusion or intraluminal suture occlusion
      in transgenic mice.

PMID- 9591851
TI  - Conley lecture. A profession of trust: reflections on a fundamental virtue.

PMID- 9591852
TI  - Vestibular function in the fetal sheep.
AB  - Little is known about the functional development of the vestibular system before
      birth. The purpose of this study was to determine whether vestibular response to
      caloric stimulation could be elicited in the fetal sheep in utero. Late
      gestational fetal sheep (n = 6) were instrumented through a midline hysterotomy.
      Copper caloric probes were inserted into the right bulla and beneath the left
      facial skin. Electrodes were placed in the skull for monitoring of electro-ocular
      activity. At least 3 days after surgery the probes were irrigated with water (100
      ml/minute) at body temperature, 46 degrees C, and 6 degrees C. Cold water
      infusion of the bulla consistently produced well-recognized, slow-phase
      deviations followed by saccades directed contralaterally, findings consistent
      with vestibular nystagmus. The direction of the response reversed with warm water
      irrigation. The response was absent with irrigation at fetal body temperature.
      Only random eye movements were observed in response to caloric stimulation of the
      facial skin, regardless of water temperature. These results demonstrate that the
      sheep vestibular system is functioning prenatally. The importance of vestibular
      function for normal fetal brain maturation may be revealed in future studies
      using this animal model.

PMID- 9591853
TI  - Sarthran preserves cochlear microcirculation and reduces temporary threshold
      shifts after noise exposure.
AB  - The cause of noise-induced hearing loss remains unclear despite years of both
      epidemiologic and experimental investigation. Among the many possible
      pathophysiologic mechanisms that may contribute to noise-induced temporary or
      permanent threshold shifts are insufficiencies in cochlear blood flow. Although
      the literature is inconsistent, several histologic and physiologic studies
      demonstrate signs of reduced circulation in the cochlea after noise exposure.
      Recent studies using computer-enhanced intravital microscopy complement these
      earlier findings. Evidence suggests that these microcirculatory events are
      mediated in part by several circulating factors, including the potent vasoactive
      peptide angiotensin. This study investigated this possibility by pretreating with
      the angiotensin receptor antagonist sarthran during noise exposure and examining
      both cochlear microcirculation and auditory sensitivity. The results of these
      experiments show noise-induced ischemia in the lateral wall of the cochlea and
      temporary threshold shifts. Treatment with sarthran prevented this noise-induced
      microcirculatory ischemia and preserved auditory sensitivity at the low
      frequencies tested. These findings support a role for the angiotensinergic system
      during noise exposure and suggest that preservation of cochlear blood flow is
      functionally related to auditory sensitivity.

PMID- 9591854
TI  - Transient-evoked otoacoustic emissions in children after cisplatin chemotherapy.
AB  - Little is known about cisplatin ototoxicity in pediatric patients. Measurement of
      otoacoustic emissions is a rapid, reproducible, objective method of evaluating
      hearing. We examined whether transient-evoked otoacoustic emissions in pediatric
      patients exposed to cisplatin in the past correlated with audiographic findings.
      Twelve patients were entered into the study (mean age at treatment 7.8 years,
      mean cumulative dose 442.5 mg/mm2, mean 7.1 doses). Hearing at 3000 Hz was
      preserved in 82.6% of patients. In the higher frequencies significant
      sensorineural hearing loss was noted: 43.5% at 4 kHz; 81.0% at 6 kHz; and 90.5%
      at 8 kHz. Transient-evoked otoacoustic emissions were measurable in 11 of 12
      patients. Middle ear disease accounted for abnormal otoacoustic emission seen in
      three patients (1 with effusion, 2 with significant negative middle ear
      pressure). When the middle ear was normal, a statistically significant
      correlation was seen between the transient-evoked otoacoustic emissions
      reproducibility and pure-tone threshold (correlation coefficient = -0.69, p =
      0.008). Increased hearing loss was also associated with young age at first dose
      of cisplatin (p = 0.044), high number of chemotherapy cycles (p = 0.042), and
      high cumulative dose (p = 0.042).

PMID- 9591855
TI  - Intratympanic gentamicin treatment for Meniere's disease.
AB  - OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of
      a modified intratympanic gentamicin technique in patients with intractable
      unilateral or bilateral Meniere's disease. METHODS: A retrospective review of 25
      consecutive patients who underwent gentamicin treatment for Meniere's disease was
      conducted between 1992 and 1996. Two separate delivery systems were used during
      this study, with the last 13 subjects undergoing placement of the new system
      (flanged polyethylene tubing). RESULTS: Follow-up averaged 23 months. Absence of
      vertigo spells was reported in 88%, and substantial control was achieved in 12%.
      Four of five patients with bilateral disease achieved complete control. Results
      for the two delivery systems were not significantly different. Absence of ice
      water caloric response was seen in 75% (15 of 20) patients. Clinically
      significant sensorineural hearing loss occurred in 5 (20%) of 25 ears.
      Nonserviceable hearing developed in only two (8%) patients. CONCLUSIONS: Our
      results support the previously reported efficacy and relative safety of
      gentamicin infusion therapy for intractable Meniere's disease. Polyethylene
      tubing may be more advantageous than T-tube delivery because of anatomic concerns
      in certain patients.

PMID- 9591856
TI  - Phase I trial of retinoic acid and cis-platinum for advanced squamous cell cancer
      of the head and neck based on experimental evidence of drug synergism.
AB  - OBJECTIVE: Cis-platinum and 13-cis-retinoic acid have received much attention in
      the treatment of head and neck squamous cell cancer. Even though they have
      different mechanisms of action, little information is available on their
      interaction. This paper reviews experimental evidence for retinoic acid-cis
      platinum synergy and presents toxicity data from patients with stage IV head and
      neck squamous cell cancer participating in a phase I trial combining 13-cis
      retinoic acid and cis-platinum. METHODS: Patients were given 13-cis-retinoic acid
      orally daily for 7 days before and daily during high-dose (150 mg/m2 per week for
      4 weeks) intraarterial cis-platinum treatment with concurrent radiation. Toxicity
      was scored with use of the cancer and leukemia group B scale. RESULTS: In the
      phase I clinical trial, 15 patients were treated to determine a maximum tolerated
      dosage for 13-cis-retinoic acid of 20 mg/day. Grade 4 hematologic toxicity was
      dose limiting in 3 of 8 patients treated with 40 mg/day and in 1 patient treated
      with 60 mg/day. There were no deaths caused by toxicity; 12 of the 15 patients
      received all four weekly doses and the remaining 3 received three doses. Of 10
      patients with fully evaluable data, all achieved a complete response at the
      primary site and 9 had a complete response in the neck. One patient had
      persistent neck disease after chemoradiation, and this tumor was removed with
      neck dissection. CONCLUSIONS: 13-Cis-retinoic acid and cis-platinum are strongly
      synergistic against head and neck squamous cell cancer in vitro. Pretreatment
      with retinoic acid results in stronger synergy than concurrent drug exposure
      alone. Preliminary clinical experience with combined retinoic acid and cis
      platinum in a design that parallels the in vitro study indicates that toxicity is
      acceptable with 13-cis-retinoic acid dosages of 20 mg/day in a high-dose
      intensity intraarterial chemoradiation regimen.

PMID- 9591857
TI  - Expression of the adenocarcinoma-related antigen recognized by monoclonal
      antibody 44-3A6 in salivary gland neoplasias.
AB  - The monoclonal antibody 44-3A6 detects a cell-surface protein that has been shown
      to be a useful marker in distinguishing adenocarcinomas from other histologic
      tumor types in a variety of tissues. The objective of this study was to determine
      whether 44-3A6 could be used as a tool in the classification of salivary gland
      neoplasms. These complex tumors share overlapping pathologic features but
      distinct clinical outcomes. This study used 44-3A6 to immunohistochemically
      describe the pattern and frequency of this antigen in salivary gland neoplasms.
      Formalin-fixed, paraffin-embedded tissue sections of 22 benign and 26 malignant
      salivary tumors were evaluated. The patient population consisted of 25 (52.1%)
      women and 23 (47.9%) men selected from archival pathology files to reflect a
      range of salivary gland diseases. Normal surrounding salivary glands were found
      to have intense focal staining almost exclusively localized to ductal luminal
      cells. There was little staining of either myoepithelial or acinar cells. A wide
      spectrum of expression was found between and within tumor types, but a trend
      toward more expression of this antigen with decreasing differentiation was seen.
      A significant increase in staining was also seen in those tumors with ductal
      differentiation (n = 41) as opposed to those with predominantly acinar (i.e.,
      acinic cell carcinoma) or myoepithelial (i.e., myoepithelioma; n = 8)
      differentiation (2.6 vs. 1.3, p < 0.05). No correlation was found between
      staining intensity and facial paralysis, pain, skin involvement, TNM stage,
      residual disease, or disease-free or total survival. Therefore this antigen
      appears to designate a duct luminal phenotype in normal and neoplastic salivary
      tissues.

PMID- 9591858
TI  - Heat shock protein and p53 expression in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Heat shock proteins have been associated with the mutant form of the
      tumor suppressor gene, TP53, and with resistance to cancer chemotherapy. METHODS:
      Archival tissues from 50 patients with head and neck squamous cell carcinoma who
      received primary surgical resection were examined for p53, HSP27, and HSP70 by
      immunohistochemistry and correlated with tumor stage, grade, and 5-year survival
      (alive or deceased). RESULTS: Both heat shock proteins were strongly expressed in
      normal mucosa and in small (T1 and T2) tumors. Thirty (60%) of tumors were
      positive for p53, 43 (86%) for HSP27, and 34 (68%) for HSP70, with no association
      between p53 and heat shock protein expression. Twenty-five patients were alive (4
      with disease), and 25 patients were deceased (9 from other causes). p53 Protein
      overexpression correlated with low-grade tumors. Only primary tumor site (i.e.,
      oral cavity > larynx > oropharynx/base of tongue) and N stage were significantly
      associated with survival. CONCLUSIONS: Heat shock proteins are expressed in
      normal upper respiratory tract squamous mucosa, and their role in carcinoma
      remains unclear. None of the markers, p53, HSP27, or HSP70, demonstrated
      prognostic significance for 5-year survival. We confirm the recognized
      association of cervical lymph node metastases with decreased survival.

PMID- 9591860
TI  - Effects of topical oral antiseptic rinses on bacterial counts of saliva in
      healthy human subjects.
AB  - Wound infections remain a significant source of morbidity in patients undergoing
      major head and neck operations that invade the aerodigestive tract. Infection
      rates have been significantly reduced by the administration of perioperative
      intravenous antibiotics; however, the incidence of infection remains unacceptably
      high. This study was undertaken to help identify an oral antiseptic that could
      significantly reduce the bacterial colony count of human saliva. A randomized,
      prospective clinical trial was conducted to analyze and compare the effects of
      Listerine antiseptic and Peridex oral rinse on the aerobic and anaerobic
      bacterial counts in healthy human subjects. Thirty healthy adult volunteers
      between the ages of 18 and 61 participated in the study. The patients were
      randomized to receive normal saline solution, Listerine antiseptic, or Peridex
      oral rinse. Aerobic and anaerobic bacterial colony counts of saliva were measured
      before treatment and at 1 and 4 hours after treatment. Both Listerine antiseptic
      and Peridex oral rinse significantly reduced bacterial counts at 1 hour after
      treatment in our volunteers. At 4 hours after treatment, Peridex oral rinse
      showed a further reduction in the bacterial colony count whereas Listerine
      antiseptic showed no difference compared with normal saline solution. At 4 hours
      after treatment, Peridex oral rinse reduced the total bacterial colony count by
      85%.

PMID- 9591859
TI  - Speech and swallowing in irradiated and nonirradiated postsurgical oral cancer
      patients.
AB  - The effect of radiation on speech and swallowing function was assessed for 18
      patients surgically treated for oral and oropharyngeal cancer. Nine patients
      received surgical intervention and postoperative radiation therapy, and nine
      received surgery only. Patients were matched regarding percentage of oral tongue
      resected, percentage of tongue base resected, locus of resection, and method of
      reconstruction. Speech and swallowing function was assessed before and at 1, 3,
      6, and 12 months after surgery following a standardized protocol. Speech tasks
      included an audio recording of a brief conversation and of a standard
      articulation test; swallowing function was examined with videofluoroscopy.
      Statistical testing indicated that overall speech function did not differ between
      the irradiated and nonirradiated patients. Irradiated patients had significantly
      reduced oral and pharyngeal swallowing performance, specifically, longer oral
      transit times on paste boluses, lower oropharyngeal swallow efficiency, increased
      pharyngeal residue, and reduced cricopharyngeal opening duration. Impaired
      function may be the result of radiation effects such as edema, fibrosis, and
      reduced salivary flow. Increased use of tongue range-of-motion exercises during
      and after radiation treatment may reduce the formation of fibrotic tissue in the
      oral cavity and may improve pharyngeal clearance by maintaining adequate tongue
      base-to-pharyngeal wall contact.

PMID- 9591861
TI  - Airway management in Pierre Robin sequence.
AB  - There is a great deal of controversy regarding the long-term management of airway
      obstruction in children with Pierre Robin sequence. All 23 pediatric
      otolaryngology fellowship programs were surveyed to determine their current
      practice patterns. Issues that were addressed included methods of evaluation of
      airway obstruction, including polysomnography, choices for home care in children
      in whom observation and positioning treatment failed, and complications of the
      various treatment modalities. The lack of unanimity among the respondents mirrors
      the controversy found in the literature. Though tracheotomy appears to be favored
      as the method of long-term management, responses from those surveyed often were
      based on emotions as much as on scientific data. This report details those
      findings and offers suggestions to clinicians involved with the management of
      patients with Pierre Robin sequence with airway compromise.

PMID- 9591862
TI  - Comparison of internal maxillary artery ligation versus embolization for
      refractory posterior epistaxis.
AB  - OBJECTIVE: This study examined the advantages and disadvantages of internal
      maxillary artery (IMA) ligation versus embolization for the treatment of
      refractory posterior epistaxis. METHODS: Thirty-nine patients underwent 42
      procedures for treatment of posterior epistaxis at the University of Cincinnati
      Medical Center between 1986 and 1994. Complication rates, failure rates,
      demographics, and the costs of IMA ligation and embolization were compared. A
      review of 20 studies published between 1973 and 1995 was done to determine the
      complication and failure rates of IMA ligation and embolization. Finally, a mail
      survey was used to determine the availability and use of IMA ligation and
      embolization by urban and rural otolaryngologists in Ohio. RESULTS: Complication
      and failure rates of IMA ligation and embolization were similar at our
      institution. In the literature review, IMA ligation had a higher complication
      rate, but fewer failures. Although the major complication rates were not
      significantly different, those associated with embolization were often more
      serious than those associated with IMA ligation. At our institution, the cost of
      IMA embolization was significantly lower than the cost of IMA ligation. Only 11%
      of Ohio otolaryngologists in nonurban areas have embolization available to treat
      posterior epistaxis. CONCLUSION: IMA ligation is more effective than IMA
      embolization but may be associated with a higher minor complication rate. The
      major complications that occur with IMA embolization are often more serious.
      Although IMA embolization was less expensive at our institution, it is
      unavailable in most nonurban regions in Ohio. Training in the use of IMA ligation
      for refractory posterior epistaxis should continue in otolaryngology residency
      training programs despite the increasing availability of embolization at
      university training centers.

PMID- 9591863
TI  - Nasal patency and the effectiveness of nasal continuous positive air pressure in
      obstructive sleep apnea.
AB  - Nasal airway obstruction may exacerbate sleep apnea and is difficult to quantify
      on clinical examination. In this study, we examined the relationship among nasal
      patency, the frequency of sleep apnea events, and effective nasal continuous
      positive air pressures. Acoustic rhinometry was used as an objective measurement
      of nasal cross-sectional areas in 76 patients without nasal symptoms who
      underwent study with diagnostic polysomnography because of obstructive sleep
      apnea. Patients with persistent obstructive sleep apnea were titrated to nasal
      continuous positive air pressure in a split night study. All subjects had a mean
      apnea/hypopnea index of 28, and those with obstructive sleep apnea had a mean
      apnea/hypopnea index of 43. Mean cross-sectional areas 1 to 4 cm into the nose
      were 1.7, 1.1, 2.1, and 2.8 cm2, respectively (F = 39, p < 0.001). However, there
      was no correlation between the apnea/hypopnea index and the cross-sectional area
      at the four distances (r = 0.03, 0.06, 0.02, and 0.02, respectively, p = not
      significant). Correlations between nasal continuous positive air pressures and
      cross-sectional areas did not reveal a significant relationship at any of the
      four sites (r = 0.09, 0.07, -0.03, 0.00, respectively). Findings in patients with
      apnea were also compared with those in patients without apnea and significant
      differences were not found (F = 0.019, p = not significant). Although it would
      seem intuitive that increased nasal obstruction is associated with the severity
      of obstructive sleep apnea and difficulty with the use of nasal continuous
      positive air pressure, this study shows that nasal patency, as measured by
      acoustic rhinometry, does not correlate with the severity of obstructive sleep
      apnea, as determined by the apnea/hypopnea index or the effective nasal
      continuous positive air pressure.

PMID- 9591864
TI  - Assessment by nasal biopsy of long-term use of mometasone furoate aqueous nasal
      spray (Nasonex) in the treatment of perennial rhinitis.
AB  - Allergic rhinitis is associated with specific histopathologic changes in the
      nasal mucosa including squamous metaplasia and local eosinophilia. Previous
      studies have shown that mometasone furoate aqueous nasal spray is effective and
      well tolerated in reducing perennial rhinitis and seasonal allergic rhinitis
      symptoms. We undertook a multicenter, open-label study to evaluate, by nasal
      biopsy, the tissue changes associated with mometasone furoate use (200
      microg/day) during a 12-month treatment period in patients with perennial
      rhinitis. Of the 69 patients enrolled in the study, 52 completed all 12 months of
      treatment. Nasal biopsy specimens obtained from patients at baseline and after
      treatment were evaluated in a blinded fashion by computerized image analysis,
      qualitative histologic examination, and immunocytochemistry. Morphologic
      examination of nasal biopsy specimens showed a decrease in focal metaplasia, no
      change in epithelial thickness, and no sign of atrophy after treatment with
      mometasone furoate. Immunocytochemical analyses of nasal biopsy specimens
      obtained before and after treatment revealed a significant decrease in major
      basic protein-positive eosinophils and tryptase-positive mast cells in the
      epithelium and lamina propria after treatment. Mometasone furoate appeared to
      attenuate the inflammatory process by reducing the extent of inflammatory cell
      infiltration, particularly of eosinophils. This study demonstrated that long-term
      administration of mometasone furoate is not associated with adverse tissue
      changes in the nasal mucosa of patients with perennial rhinitis.

PMID- 9591865
TI  - Comparison of concentric needle versus hooked-wire electrodes in the canine
      larynx.
AB  - BACKGROUND: The use of a specific electrode type in laryngeal electromyography
      has not been standardized. Laryngeal electromyography is usually performed with
      hooked-wire electrodes or concentric needle electrodes. Hooked-wire electrodes
      have the advantage of allowing laryngeal movement with ease and comfort, whereas
      the concentric needle electrodes have benefits from a technical aspect and may be
      advanced, withdrawn, or redirected during attempts to appropriately place the
      electrode. OBJECTIVES: This study examines whether hooked-wire electrodes permit
      more stable recordings than standard concentric needle electrodes at rest and
      after large-scale movements of the larynx and surrounding structures. A
      histologic comparison of tissue injury resulting from placement and removal of
      the two electrode types is also made by evaluation of the vocal folds. METHODS:
      Electrodes were percutaneously placed into the thyroarytenoid muscles of 10 adult
      canines. Amplitude of electromyographic activity was measured and compared during
      vagal stimulation before and after large-scale laryngeal movements. Signal
      consistency over time was examined. Animals were killed and vocal fold injury was
      graded and compared histologically. RESULTS: Waveform morphology did not
      consistently differ between electrode types. The variability of electromyographic
      amplitude was greater for the hooked-wire electrode (p < 0.05), whereas the mean
      amplitude measures before and after large-scale laryngeal movements did not
      differ (p > 0.05). Inflammatory responses and hematoma formation were also
      similar. CONCLUSIONS: Waveform morphology of electromyographic signals registered
      from both electrode types show similar complex action potentials. There is no
      difference between the hooked-wire electrode and the concentric needle electrode
      in terms of electrode stability or vocal fold injury in the thyroarytenoid muscle
      after large-scale laryngeal movements.

PMID- 9591866
TI  - Analysis of cellular location and concentration in vocal fold lamina propria.
AB  - Studies have shown that the lamina propria plays an important role in voice
      production. Recent studies have analyzed the presence of different proteins and
      quantified their extent in the lamina propria, but no similar study has yet been
      done on cellular makeup. The distribution of three different cell types in the
      lamina propria of 22 human vocal folds was studied. These types are fibroblasts,
      macrophages, and myofibroblasts. The roles of these cells in the extracellular
      matrix are described. Their distribution was quantified with use of an image
      analysis system. We arbitrarily divided the lamina propria into five sections
      (each representing 20% of the lamina propria) and compared cell numbers among
      these sections. Gender comparisons were also made. From these studies it is
      evident that the cellular distribution in the lamina propria is not uniform.
      Fibroblasts were more abundant in the deepest 20% of the lamina propria (p <
      0.008), myofibroblasts were more abundant in the most superficial 20% (p <
      0.016), and in the 36% of our samples that contained macrophages in the lamina
      propria, there was a significantly higher number of macrophages in the first 20%
      of the lamina propria (p < 0.003). The only significant gender difference was
      that women had twice as many macrophages in the most superficial 20% of the
      lamina propria as men (p < 0.05). The higher myofibroblast activity in the first
      20% could indicate that the superficial layer is a region of constant repair. The
      increased number of macrophages in the superficial layer likely indicates an
      inflammatory response to inhalants (because of the role of macrophages in the
      inflammatory response and the fact that only 36% of the patients showed any
      macrophage activity at all).

PMID- 9591867
TI  - Comparative efficacy of terfenadine, loratadine, and astemizole in perennial
      allergic rhinitis.
AB  - Nonsedating H1 antihistamines such as terfenadine, loratadine, and astemizole are
      widely prescribed for the treatment of allergic rhinitis. The comparative
      efficacy of these agents has not been thoroughly studied. We studied 14 subjects
      in an open-label four-way crossover trial. Patients were recruited from an
      outpatient allergy clinic. Inclusion criteria were documented rhinitis symptoms
      for at least 2 years before the study and skin-test positivity in response to
      perennial allergens. Each subject underwent sequential 2-week trials of each of
      four H1 antihistamines: terfenadine, loratadine, astemizole, and
      chlorpheniramine. No placebo was included. Outcome measures were subjective
      rhinitis symptom scores, overall efficacy scores, and concomitant pseudoephedrine
      use. In addition, nasal-examination scores were obtained by way of physician
      assessment at the end of each 2-week trial, and side effects were tabulated.
      Nasal-examination scores for each of the four H1 antihistamines were
      significantly better than the baseline scores (p < 0.05). No statistically
      significant differences in rhinitis symptom scores, overall efficacy scores, or
      concomitant pseudoephedrine use were noted. We detected no clinically significant
      differences in efficacy among terfenadine, loratadine, astemizole, and
      chlorpheniramine in the treatment of perennial allergic rhinitis.

PMID- 9591868
TI  - Aminoglycoside ototoxicity: prevention in sight?
AB  - Despite the development of new antibiotics, the aminoglycosides are still
      indispensable in the treatment of life-threatening diseases. Worldwide they are
      the most commonly used antibiotics, and their use is expected to increase in the
      wake of the rising incidence of tuberculosis. The most prominent side effects of
      aminoglycoside treatment--cochlear, vestibular, and renal impairment--are a
      limiting factor in the utility of these drugs. A novel mechanism of gentamicin
      ototoxicity is based on observations of iron chelation and free radical
      formation. Predictions from this mechanism have led to successful therapeutic
      prevention of ototoxicity by use of iron chelators and radical scavengers in
      guinea pigs. The drugs used for this interventive treatment affect neither serum
      levels of gentamicin nor its antibacterial efficacy. Because these drugs are in
      clinical use, the suggested protective treatment should lend itself to clinical
      trials.

PMID- 9591869
TI  - Aberrant internal carotid artery causing erosion of the otic capsule: an unusual
      cause of pulsatile tinnitus.

PMID- 9591870
TI  - Congenital nasal pyriform aperture stenosis in the monozygotic twin of a child
      with holoprosencephaly.

PMID- 9591871
TI  - Approach to branchial pouch anomalies that cause airway obstruction during
      infancy.

PMID- 9591872
TI  - Clinical significance of compound cilia.

PMID- 9591873
TI  - Endoscopic management of a chronic ethmoid and sphenoid sinus foreign body.

PMID- 9591874
TI  - Primary extracranial meningioma of the temporal bone.

PMID- 9591875
TI  - Facial nerve paralysis in acute otitis media: cause and management revisited.

PMID- 9591877
TI  - Toxic shock syndrome after mastoidectomy.

PMID- 9591876
TI  - Hantavirus infection: a possible cause of delayed sensorineural hearing loss.

PMID- 9591878
TI  - Effect of increased inner ear pressure on middle ear mechanics.
AB  - Velocity of malleus, umbo, and stapes footplate in response to stepwise increases
      up to +400 mm H2O in hydrostatic pressure of the inner ear was investigated in 10
      fresh human temporal bones by using a laser Doppler interferometer. The sound
      pressure input was 114 dB SPL, and the frequency range was 0.4 to 5.0 kHz. Static
      displacement of these sites was also measured by a video measuring system. When
      the inner ear pressure was increased, the malleus and stapes moved outward.
      Amplitude of umbo velocity decreased below 1.0 kHz with a slight increase around
      2.0 kHz, whereas stapes velocity decreased at all frequencies with the major
      effect below 1.0 kHz. The phase angle of malleus umbo velocity advanced markedly
      in response to the increased inner ear pressure between 1.0 and 1.4 kHz. Change
      in the vibration of the umbo was thought to be primarily caused by an increased
      stiffness of the middle ear conduction system, and that of the stapes was caused
      by distention of the annular ligament and increased cochlear impedance produced
      by the increased inner ear pressure. These changes in TM vibration and its phase
      angle may help detect indirectly an elevation of inner ear pressure.

PMID- 9591880
TI  - Functional differences between the two bellies of the cricothyroid muscle.
AB  - The contraction of the cricothyroid (CT) muscle, which results in a decrease in
      the distance between the thyroid and cricoid cartilages, is considered to be the
      main factor in lengthening the vocal folds. This is achieved by rotation of the
      CT joint. The CT muscle is composed of two distinct bellies, the pars recta and
      the pars obliqua. The function of each subunit is not clearly understood,
      although it is believed that they act differently because their fibers run in
      different directions. To clarify the function of the two bellies in phonation,
      the fundamental frequency (F0), vocal intensity, subglottic pressure, vocal fold
      length, and CT distance were measured using an in vivo canine laryngeal model. On
      the basis of these measurements, we demonstrated that the two bellies are varied
      in their effect on raising the pitch, rotation, and forward translation of the CT
      joint. The stimulation of the pars recta nerve resulted in a greater increase in
      the F0 value compared with that of pars obliqua. The combined activity of the
      pars recta and pars obliqua is important in adjustment of the vocal fold length.
      The CT approximations directed parallel to the pars recta and pars obliqua
      simultaneously were more effective in elevation of the pitch than the
      approximation placed parallel to the pars recta only. This finding may be
      clinically significant with regard to CT approximation thyroplasty in human
      trails.

PMID- 9591879
TI  - Myringoplasty in children: factors influencing surgical outcome.
AB  - Age, size, and site of perforation, condition of the ear, status of the
      contralateral ear, grafting materials, and more are considered factors
      influencing the success rates in myringoplasties in children. The ambivalence in
      results is mainly due to nonhomogeneous patient groups. In an effort to compose
      groups as homogeneous as possible for analysis of influencing factors, a
      retrospective study of 51 pediatric myringoplasty cases (51 ears) was undertaken.
      All patients had perforations caused by simple chronic otitis media. The overall
      surgical success rate was 82.3% at 18 months, and for young (5 to 10 years) and
      older (11 to 16 years) children it was 77.2% and 86.2%, respectively. Anterior,
      central, and total perforations healed without significant differences. Outcome
      in unilateral perforations was better than bilateral: 96.9% and 55%, respectively
      (p < 0.01). Discharging ears (100%) healed better compared with dry ears (75%) (p
      < 0.05). Analysis of the literature also revealed significant difference in
      success rates of discharging and dry ears: 92.5% and 80.6%, respectively (p <
      0.01). We conclude that, contrary to comments in the literature, discharging ears
      in children favor good outcome and they should be operated on regardless of age
      and site of perforation. However, in bilateral perforations results may not be so
      rewarding.

PMID- 9591881
TI  - Evaluation of expiratory effort on dysphonic patients on increasing vocal
      intensity.
AB  - It is conceivable that the subjects who have phonatory disorders, in comparison
      with normal individuals, exert a greater expiratory effort when phonating loudly.
      Furthermore, we presume that the extent and pattern of the changes in the
      expiratory effort for increasing vocal intensity may vary according to the types
      of laryngeal lesions. To prove these hypotheses, we investigated the changes in
      expiratory effort for increments of the vocal intensity by measuring the
      expiratory lung pressure. The subjects included 10 each of normal controls,
      patients with Reinke's edema, and those with recurrent laryngeal nerve paralysis.
      For the normal controls, the increase in vocal intensity was achieved by slightly
      increasing the expiratory lung pressure. The patients with Reinke's edema showed
      a greater increase in expiratory lung pressure, as compared with the normal
      group. The patients with recurrent laryngeal nerve paralysis exhibited greater
      expiratory effort with extreme increases in airflow than normal group for louder
      phonation. It was concluded that the subjects who have phonatory disorders, in
      comparison with normal individuals, require a greater expiratory effort. This
      phonatory function test with an increase in voice intensity made the aerodynamic
      pathologic condition clearer.

PMID- 9591882
TI  - Does surgery improve the survival of patients with advanced anaplastic thyroid
      carcinoma?
AB  - Anaplastic thyroid carcinoma is one of the most lethal neoplasms, with poor
      prognosis being reported by most authors. The benefits of surgery for most cases
      of advanced disease remain controversial. In this study we asked the following
      question: Does surgical intervention alter outcomes for patients with advanced
      anaplastic thyroid carcinoma? Forty-six patients with advanced anaplastic thyroid
      carcinoma were analyzed. There were 20 patients with advanced localized disease
      (group 1), 15 of whom received surgery. Of the other 26 patients with evidence of
      distant metastases (group 2), 13 received surgery. For group 1 patients, the mean
      survival was 12.8 months versus 8.6 months in the surgical and nonsurgical
      subgroups (p = 0.46). For group 2 patients, the mean survival was 3.5 months
      versus 2.8 months in the surgical and nonsurgical subgroups (p = 0.72). These
      data suggest that surgery does not improve survival for patients with advanced
      anaplastic thyroid carcinoma. In conclusion, the mean survival showed no
      significant differences between surgical and nonsurgical patients (p = 0.43).
      This study suggests that surgical resection does not improve the survival of
      patients with advanced anaplastic thyroid carcinoma.

PMID- 9591884
TI  - Fibrovascular polyp of the esophagus.

PMID- 9591883
TI  - Stress fracture of the clavicle after selective neck dissection.

PMID- 9591886
TI  - Hypoglossal nerve conduction study by transcranial magnetic stimulation in normal
      subjects.

PMID- 9591885
TI  - Cutaneous horn of the auricle.

PMID- 9591887
TI  - Familial clustering of nasopharyngeal carcinoma.

PMID- 9591888
TI  - MRI in sudden sensorineural hearing loss.

PMID- 9591889
TI  - Tissue examination in obliteration technique and outpatient setting.

PMID- 9591890
TI  - Previous angina reduces in-hospital death in patients with acute myocardial
      infarction.
AB  - There is little information on how previous angina influences in-hospital deaths
      secondary to acute myocardial infarction (MI). This study evaluated the causes of
      in-hospital deaths in MI patients with and without previous angina. A total of
      2,264 consecutive patients were admitted to our hospital due to acute MI. These
      patients were divided into 2 groups according to the presence or absence of prior
      MI. Both groups were further divided according to the presence or absence of
      previous angina. The causes of in-hospital deaths were classified into 4
      categories: (1) cardiogenic shock or congestive heart failure, (2) cardiac
      rupture, (3) arrhythmia, and (4) other causes. In patients with a first MI, the
      in-hospital mortality rate was lower in patients with previous angina than those
      without (6.9% vs 11.4%, p <0.01). There was no significant difference between
      these patients with and without previous angina in in-hospital deaths due to
      cardiogenic shock or congestive heart failure, arrhythmia, or other causes. Death
      due to cardiac rupture was less frequent in patients with previous angina (1.4%
      vs 5.0%, p <0.01). In patients with prior MI, the in-hospital mortality rate was
      lower in patients with than without previous angina (17.7% vs 25.3%, p <0.05). In
      contrast to patients with their first MI, there was a trend toward a lower
      incidence of in-hospital death due to cardiogenic shock or congestive heart
      failure in patients with previous angina (12.8% vs 19.0%, p = 0.05). There were
      no significant differences in in-hospital deaths due to cardiac rupture,
      arrhythmia, and other causes between the 2 subgroups. In multivariate analysis,
      previous angina was an independent predictor of in-hospital death. Thus, in
      hospital deaths after acute MI in patients with previous angina were less because
      of less cardiac rupture in patients with a first MI and less cardiogenic shock or
      congestive heart failure in patients with prior MI.

PMID- 9591891
TI  - The "warm-up" phenomenon occurs in patients with chronic stable angina but not in
      patients with syndrome X.
AB  - Most patients with chronic stable angina show an improvement in ischemic
      threshold when a second exercise test is performed a few minutes after a first
      positive test. In this study we evaluated whether this "warm-up" phenomenon also
      occurs in patients with syndrome X. We performed 2 consecutive exercise tests in
      14 patients with chronic stable angina and 11 patients with syndrome X. The
      second exercise test was performed after 10 minutes from the end of the first
      one, always after complete recovery to baseline of ST segment. In patients with
      stable angina, heart rate (108+/-18 vs 99+/-16 beats/min, p = 0.005), rate
      pressure product (17,020+/-4,541 vs 15,215+/-3,734 beats/min x mm Hg, p = 0.028),
      and exercise time (587+/-297 vs 444+/-244 seconds, p = 0.002) at 1-mm ST
      depression were higher in the second test than in the first one and a significant
      improvement in these parameters during the second test was also observed at peak
      exercise. Conversely, in patients with syndrome X, there were no significant
      differences between the 2 tests in heart rate (128+/-18 vs 131+/-23 beats/min),
      rate-pressure product (19,922+/-5,153 vs 19,390+/-5,654 beats/min x mm Hg), and
      exercise time (592+/-243 vs 566+/-228 seconds) at 1-mm ST-segment depression.
      Similarly, in this group of patients, no significant differences in exercise
      variables between the 2 tests were observed at peak exercise. Thus, unlike
      patients with chronic stable angina, patients with syndrome X have no evidence of
      warm-up in response to repeated exercise testing.

PMID- 9591892
TI  - Value of the addition of amlodipine to atenolol in patients with angina pectoris
      despite adequate beta blockade.
AB  - Anginal patients who remain symptomatic despite optimally dosed beta blockade may
      also be given dihydropyridine calcium antagonists. This treatment regimen was
      examined in a double-blind parallel, randomized, controlled study in 147 patients
      with angina and positive bicycle exercise tests despite optimal beta blockade
      with atenolol (heart rate at rest <60 beats/min). Patients were randomized to
      atenolol and/or placebo (control), and atenolol and/or amlodipine. The main
      outcome measurement was exercise tolerance after 8 weeks compared with baseline.
      After 8 weeks, no significant differences in time to 0.1-mV ST-segment
      depression, time to chest pain, and time to end of exercise were observed. The
      number of patients with chest pain during exercise decreased significantly in the
      amlodipine group (p = 0.04 vs controls). The subgroup of patients with an early
      (<6 minutes) onset of chest pain at baseline showed a significant increase in
      time to chest pain after amlodipine (p = 0.0001 vs controls). In the amlodipine
      group, ST depression and rate-pressure product at submaximum comparable workload
      decreased to 0.4 mm (0.56) (p = 0.03 vs controls) and 1.223 (2.652) beats/ min x
      mm Hg (p = 0.01 vs controls). The number of patients in each group with adverse
      events was not different. The addition of amlodipine to the treatment of patients
      with myocardial ischemia, despite optimal beta blockade, is well tolerated and
      may lead to improvement in symptomatic anginal patients, who have a rapid onset
      of exercise-induced ischemia.

PMID- 9591893
TI  - Amlodipine versus diltiazem as additional antianginal treatment to atenolol.
      Centralised European Studies in Angina Research (CESAR) Investigators.
AB  - The antianginal efficacy and tolerability of amlodipine and diltiazem were
      compared in a double-blind randomized trial of 97 patients with angina resistant
      to atenolol alone. Both amlodipine and diltiazem significantly reduced the
      frequency of angina attacks (p <0.001) and glyceryl trinitrate consumption (p
      <0.05 to p <0.01). During Holter monitoring, both treatments reduced the overall
      frequency of ambulatory myocardial ischemia, although changes did not reach
      statistical significance. Exercise test parameters (total exercise time, time to
      angina, time to ST depression, and maximum ST depression) tended to improve with
      both treatments, but changes did not achieve statistical significance relative to
      baseline or to each other. Both drugs were generally well tolerated. Adverse
      events occurred in 15 patients in the amlodipine group (30%) and in 17 patients
      in the diltiazem group (36%), but patients taking diltiazem reported almost twice
      as many adverse events (30) patients taking amlodipine (18). Quality of life, as
      assessed by total Nottingham Health Profile Scores, was not significantly
      different between treatments. The addition of either once-daily amlodipine or
      twice-daily sustained release diltiazem improved symptoms in patients with angina
      resistant to atenolol alone, but diltiazem was associated with more frequent and
      more serious adverse events.

PMID- 9591894
TI  - Effect of diltiazem on sympathetic hyperactivity in patients with vasospastic
      angina as assessed by spectral analysis of arterial pressure and heart rate
      variability.
AB  - The autonomic nervous system importantly regulates coronary arterial tone and
      vascular resistance. To evaluate a role of autonomic nervous activity and the
      effects of calcium antagonist in patients with vasospastic angina (VSA), 13 VSA
      patients with patent coronary arteries (58+/-8 years) and 8 normal subjects (58+/
      12 years) were studied. Arterial pressure and electrocardiogram were continuously
      recorded with the patient in a supine position under controlled respiration (0.2
      Hz). Low-frequency (LF) and high-frequency (HF) components of the beat-to-beat
      variabilities of systolic arterial pressure and RR interval were then estimated
      by autoregressive power spectral analysis. The LF power (normalized unit) of both
      systolic arterial pressure (0.53+/-0.17 vs 0.30+/-0.17, p < 0.01) and RR
      variabilities (0.51+/-0.20 vs 0.31+/-0.16, p < 0.05) in patients with VSA were
      greater than that in normal subjects. There was no significant difference in the
      HF power. Seven patients with VSA who were treated with diltiazem (60 to 200
      mg/day) had normalized LF power (normalized unit) of both systolic arterial
      pressure (0.62+/-0.12 vs 0.33+/-0.16, p < 0.01) and RR variabilities (0.55+/-0.23
      vs 0.36+/-0.14, p < 0.05), together with clinical improvement. An increased
      sympathetic vasomotor tone and cardiac sympathetic predominance may play an
      important role in patients with VSA. Diltiazem improves these sympathetic
      hyperactivities.

PMID- 9591895
TI  - Comparison of electron-beam computed tomography and intracoronary ultrasound in
      detecting calcified and noncalcified plaques in patients with acute coronary
      syndromes and no or minimal to moderate angiographic coronary artery disease.
AB  - We compared intracoronary ultrasound (ICUS) and electron-beam computed tomography
      (EBCT) on a coronary segmental basis in 40 consecutive patients with acute
      coronary syndromes and no or minimal to moderate angiographic disease (53+/-10
      years; 34 men, 6 women). ICUS was used to define plaques, and EBCT was used to
      quantify coronary calcium (using a threshold of a CT density > 130 Hounsfield
      units in an area > 1.03 mm2). In a site-by-site analysis, coronary segments were
      defined as normal if both methods were negative, as containing noncalcified
      plaques if only ICUS was positive, and as containing calcified plaques if both
      methods were positive. A total of 222 coronary segments were analyzed (5.6+/-1.9
      segments per patient). In 36 patients (90%), a total of 95 segments with plaques
      were identified, whereas in 4 patients (10%), only normal segments were seen. Of
      the 95 segments with plaques, 61 (64%) were calcified, and 34 (36%) were
      noncalcified. There was a linear relationship between the number of segments with
      calcified and with noncalcified plaques (r = 0.86, p <0.0001), but the mean
      relative frequency of segments with calcified plaques (55+/-38%) was highly
      variable. Calcium was found in 15 of 16 patients (93%) with 3 or more segments
      with plaques, while it was found in only 12 of 20 patients (60%) with one or 2
      segments with plaques (p = 0.026). Younger age, higher low-density lipoprotein
      cholesterol levels, diabetes, and active smoking predicted a higher relative
      frequency of segments with noncalcified plaques. Thus, in patients with acute
      coronary syndromes but no angiographically critical stenoses, there is a linear
      relationship between segments with calcified plaques versus segments with
      noncalcified plaques. However, while the mean ratio of these segments is close to
      1:1, it is highly variable among individual patients.

PMID- 9591896
TI  - Clinical outcome at six months of coronary stenting followed by ticlopidine
      monotherapy.
AB  - Antiplatelet therapy has been shown to be superior to oral anticoagulation after
      coronary stent implantation. Different regimens for postinterventional
      antiplatelet therapy have been proposed. A combination of ticlopidine and aspirin
      has gained the most widespread use. The relative merit of the different compounds
      in this combination remains unclear. There are several, partly conflicting,
      reports on coronary stent implantation followed by aspirin alone, but data on
      ticlopidine monotherapy are scarce. We conducted a prospective trial of elective
      coronary stenting followed by ticlopidine monotherapy in 263 consecutive,
      unselected patients. One-, 2-, and 3-vessel disease was present in 42.9%, 42.6%,
      and 14.5% of patients, respectively. We deployed a total of 322 stents. All
      patients received 250 mg of ticlopidine twice daily for up to 6 months. The
      clinical end points encountered during the hospital stay and at 5.9+/-2.9 months,
      respectively, were: death (2 [0.8%] and 2 [0.8%]); myocardial infarction (5
      [1.9%] and 4 [1.5%]); target vessel occlusion (2 [0.8%] and 4 [1.5%]); bypass
      surgery (0 and 2 [0.8%]); and repeat angioplasty (2 [0.8%] and 52 [19.8%]). There
      was 1 vascular surgery (0.4%) and 4 (1.5%) non-procedure-related ischemic
      cerebrovascular events at follow-up. We conclude that coronary stent deployment
      followed by ticlopidine monotherapy is safe and effective in an unselected
      population. The overall clinical outcome at 6 months is good and comparable to
      that of patients treated with combined antiplatelet therapy. Ticlopidine
      monotherapy may be a safe alternative for patients with contraindications to
      aspirin.

PMID- 9591897
TI  - Clinical and angiographic outcome of Micro Stent II implantation in native
      coronary arteries.
AB  - To evaluate immediate success and 6-month restenosis rate, 70 Micro Stents II
      were implanted for 65 stenoses in 63 patients (age 59+/-9 years). Stable angina
      pectoris was present in 47% of the patients (38% class I to III; 9% class IV),
      whereas 32% had postinfarction angina and 21% had unstable angina. Indications
      for stent implantation were elective in 62% and semi-elective in 38% of the
      patients. Sixty-two percent of the patients received ticlopidin and
      acetylsalicylic acid for 28 days, whereas 38% of the patients received only
      acetylsalicylic acid. All stents were deployed successfully at the target site.
      Subacute closure occurred in 2 patients (3%), both of whom were not treated with
      ticlopidin. Two other patients (3%) developed non-Q-wave infarction after side
      branch occlusion during the procedure. The minimum lumen diameter increased from
      1.0+/-0.5 mm to 2.8+/-0.4 mm after stent implantation. At follow-up the loss in
      diameter was 0.9+/-0.6 mm, indicating a net gain of 0.9+/-0.8 mm. Late clinical
      events (4 weeks to 6 months) were coronary angioplasty of a stented segment (3%),
      coronary angioplasty of a nonstented segment (10%), and coronary artery bypass
      grafting (2%). No deaths or myocardial infarction occurred. The procedural
      success rate was 94% and the event-free survival at 6-month follow-up was 79%.
      Micro Stent II implantation can be done with a high rate of immediate success and
      good 6-month outcome. The Micro Stent II has proven to be a versatile device that
      can also be used in patients with less favorable coronary anatomy or lesion
      characteristics.

PMID- 9591898
TI  - Effect of dual-chamber pacing with automatic rate-drop sensing on recurrent
      neurally mediated syncope.
AB  - We tested the hypotheses that a dual-chamber pacemaker that paces when intrinsic
      rate drops abruptly would reduce the number of syncopal spells and improve the
      quality of life in patients with highly recurrent neurally mediated syncope.
      Twelve patients with highly frequent neurally mediated syncope and at least 1
      syncopal spell after tilt testing received dual-chamber pacemakers with automatic
      rate-drop sensing. The pacemakers were implanted 17+/-26 months after tilt
      testing, and the patients then were followed for 12+/-2 months. We compared the
      time to the first recurrence of syncope, syncope frequency, and quality of life
      for the 2 periods between tilt testing and pacemaker implantation, and between
      implantation and last follow-up. Only 6 of 12 patients fainted after pacemaker
      insertion. The median time to syncope recurrence before and after pacing was 7
      days and 5.3 months, respectively. The geometric mean frequency of faints before
      and after pacing was 5.0 spells/month (95% confidence interval 2.7 to 9.2) and
      0.30 spells/month (95% confidence interval 0.2 to 0.4), p <0.001. After 6 months
      the mean perception of health on the 100-point EuroQol scale rose from 55 to 82
      (p = 0.003), and the general health perception on the SF-36 scale rose from 51 to
      72 (p = 0.005). Permanent dual-chamber pacing with automatic rate-drop sensing in
      patients with highly frequent syncope is associated with a marked reduction in
      the likelihood of syncope and a marked improvement in quality of life.

PMID- 9591899
TI  - Safety of long-acting dihydropyridine calcium channel blockers in hypertensive
      patients.
AB  - Issues raised recently concerning the safety of calcium channel blockers (CCBs)
      prompted an analysis of the occurrence of cardiovascular events and death in the
      Pfizer Inc. hypertension clinical trial databases for amlodipine (Norvasc) and
      nifedipine in the gastrointestinal therapeutic system (GITS) formulation
      (Procardia XL). Prospectively defined analyses of data from comparative and
      noncomparative trials of amlodipine and nifedipine GITS were conducted. Outcome
      measures included cardiovascular and noncardiovascular deaths, and adverse
      cardiovascular events including new/worsened angina, myocardial infarction (MI),
      serious arrhythmia, stroke, congestive heart failure, and bleeding. Among all
      amlodipine-treated patients (n = 32,920), the incidence rates for all-cause
      death, MI, and new/worsened angina were 3.0, 3.3, and 1.6/1,000 patient-years of
      exposure, respectively. Among those in comparative trials alone (n = 4,126), the
      all-cause death rate was 4.1/1,000 patient-years, which was comparable to that of
      other non-CCB agents and significantly less than that of other CCBs (23.8/1,000
      patient-years, p = 0.015), although the difference in rates represents only 2
      deaths. Among all nifedipine-GITS-treated patients (n = 2,645), the rate of all
      cause death was 4.1/1,000 patient-years, of MI 6.5/1,000 patient-years, and of
      new/ worsened angina 5.7/1,000 patient-years. The incidence rates for MI and
      other cardiac events were low in these hypertension trials, and did not differ
      among treatment groups in either the amlodipine or nifedipine GITS comparative
      analyses. In the clinical trial databases analyzed, there is no signal suggesting
      excessive risk of death or cardiovascular events for hypertensive patients
      treated with amlodipine or nifedipine GITS.

PMID- 9591900
TI  - Reduction of QT and QTc dispersion during long-term treatment of systemic
      hypertension with enalapril.
AB  - We report, in conjunction with other findings, the evolution of the dispersion of
      QT and QTc in patients who for the last 7 years have been treated with enalapril
      for systemic hypertension with left ventricular (LV) hypertrophy. Twenty-four
      essential hypertensive patients who had received no previous treatment took
      enalapril (20 mg twice daily) for 7 years. In a pretreatment placebo phase and 8
      weeks and 1, 3, 5, 6, and 7 years after the start of therapy, cardiovascular
      parameters were determined by two-dimensional guided M-mode echocardiography, and
      the QT interval and corrected QT interval (QTc) and their dispersions were
      obtained from amplified standard 12-lead electrocardiograms. Therapy rapidly
      reduced blood pressure (BP) from 156/105 mm Hg to normal values; at 7-year follow
      up, BP was 130/84 mm Hg (p <0.001 with respect to the placebo phase). LV mass
      index decreased progressively until at 5-year follow-up the reduction had reached
      39% (p <0.001), after which neither LV mass index nor any structural parameter
      underwent any further significant change. LV pump function was also significantly
      better after 7 years of treatment. During this time, QT and QTc decreased
      significantly, as did the dispersion of both QT (from 61+/-21 to 37+/-14 ms) and
      QTc (from 67+/-27 to 41+/-16 ms). We conclude that long-term enalapril treatment
      of hypertensive patients with LV hypertrophy not only induces marked regression
      of LV mass and improved LV systolic function, but also reduces the dispersions of
      QT and QTc, which probably reduces the likelihood of ventricular arrhythmias and
      improves prognosis.

PMID- 9591901
TI  - Comparison of vena contracta width by multiplane transesophageal echocardiography
      with quantitative Doppler assessment of mitral regurgitation.
AB  - Mitral regurgitation (MR) severity is routinely assessed by Doppler color flow
      mapping, which is subject to technical and hemodynamic variables. Vena contracta
      width may be less influenced by hemodynamic variables and has previously been
      shown to correlate with angiographic estimates of MR severity. This study was
      performed to compare mitral vena contracta width by multiplane transesophageal
      echocardiography (TEE) with simultaneous quantitative Doppler echocardiography in
      35 patients with MR. The vena contracta width was measured at the narrowest
      portion of the MR jet as it emerged through the coaptation of the leaflets; it
      was identified in 97% of the patients. Vena contracta width correlated well with
      regurgitant volume (R2 = 0.81) and regurgitant orifice area (R2 = 0.81) by
      quantitative Doppler technique. A vena contracta width > or = 0.5 cm always
      predicted a regurgitant volume >60 ml and an effective regurgitant orifice area >
      or = 0.4 cm2 in all patients. A vena contracta width < or = 0.3 cm always
      predicted a regurgitant volume <45 ml and a regurgitant orifice area < or = 0.35
      cm2. Thus, vena contracta width by multiplane TEE correlates well with mitral
      regurgitant volume and regurgitant orifice area by quantitative Doppler
      echocardiography and provides a simple method for the identification of patients
      with severe MR.

PMID- 9591902
TI  - Noninvasive evaluation of left ventricular diastolic function in hypertrophic
      cardiomyopathy.
AB  - Diastolic dysfunction is common in hypertrophic cardiomyopathy (HC). Previous
      studies suggest that Doppler transmitral flow velocity profiles, and the left
      atrial (LA) M-mode echogram can be used noninvasively to evaluate left
      ventricular (LV) diastolic function. However, this has not been proved in HC. In
      this study we determined the relation of Doppler transmitral flow velocity
      profiles and the LA M-mode echograms to invasive indexes of LV diastolic function
      in patients with HC. We studied 25 patients with HC, while off drugs, and
      calculated LA global and active fractional shortening and the slope of both early
      and late displacement of the posterior aortic wall during LA emptying by M-mode
      echocardiography. We calculated peak velocity of early (E) and atrial (A)
      filling, E to A ratio, and E-wave deceleration time by pulsed Doppler
      echocardiography, and simultaneous radionuclide angiography, LV pressures, time
      constant of isovolumic relaxation tau, and the constant of chamber stiffness k by
      cardiac catheterization. The time constant of isovolumic relaxation tau
      correlated with the slope of early posterior aortic wall displacement (r = 0.59;
      p <0.01). LV end-diastolic pressure correlated with global LA fractional
      shortening (r = -0.75; p <0.001); the constant of chamber stiffness k correlated
      with active LA fractional shortening (r = -0.53; p <0.02). In a subset of 13
      patients, in whom echocardiography and cardiac catheterization were performed
      simultaneously, similar results were found. LA M-mode recordings provide a more
      reliable noninvasive assessment of diastolic function in HC than mitral Doppler
      indexes.

PMID- 9591903
TI  - Usefulness of electron beam computed tomography in children with heterotaxy
      syndrome.
AB  - Children with heterotaxy syndrome frequently have complex cardiac and noncardiac
      malformations requiring detailed diagnostic evaluation for management planning.
      Direct delineation of these structures by electron beam computed tomography
      (EBCT) is validated as a means of diagnosis. From July 1995 to March 1997, 32
      patients (16 girls, 16 boys) with clinically impressed heterotaxy syndrome were
      enrolled in this study. After evaluation by echocardiography, EBCT studies were
      performed. Interpretation of cardiac anomalies was performed by sequential
      analysis based on these cross-sectional images. The diagnoses were subsequently
      confirmed by angiocardiography and surgical findings. Twenty-eight patients had
      bilateral trifurcated bronchi, and most of these (24 of 28) did not have a
      spleen. Four patients had bilateral bifurcated bronchi, 2 patients had
      polysplenia, and the other 2 patients had a lobulated single spleen. We found
      that laterality could be identified by EBCT in all patients. Comparison of
      diagnostic yield between echocardiography, catheterization, and EBCT showed that
      EBCT is superior to echocardiography and catheterization in demonstration of
      pulmonary venous anatomy and presence of a very small rudimentary ventricle. In
      addition, associated visceral, bronchopulmonary, mediastinal, and intracardiac
      anomalies could all be clearly delineated by EBCT at the same time. Thus, EBCT is
      a promising complementary modality for an overall understanding of heterotaxy
      syndrome.

PMID- 9591904
TI  - Early and late results after repair of aortopulmonary septal defect and
      associated anomalies in infants <6 months of age.
AB  - The Richardson classification system for aortopulmonary septal defect (APSD)
      includes simple defects between the ascending aorta and pulmonary trunk (type I),
      defects extending distally to include the origin of the right main pulmonary
      artery (type II), and anomalous origin of the right main pulmonary artery from
      the ascending aorta with no other aortopulmonary communication (type III). These
      are rare lesions that must be repaired in early infancy to avoid development of
      pulmonary vascular disease. Few reports have focused on patients with complex,
      associated lesions who underwent repair in early infancy. Between 1972 and 1995,
      24 patients with Richardson type I (n = 11), II (n = 7), or III (n = 6) defects
      underwent repair at ages ranging from 2 to 172 days (median 34). Twelve patients
      had complex, associated anomalies, including interrupted or hypoplastic arch (n =
      9), tetralogy of Fallot with (n = 1) or without (n = 1) pulmonary atresia, and
      transposition of the great arteries (n = 1). The most recent 7 patients were
      diagnosed by echocardiography without cardiac catheterization. There were no
      early or late deaths among the 12 patients with simple APSD. Four patients with
      complex, associated lesions died in the early postoperative period and another
      died 4 months after surgery. All 6 surviving patients with interrupted arch have
      had recurrent obstruction at the arch repair site, although reintervention for
      this reason has been performed in only 2 patients. Altogether, 6 early survivors
      have required reintervention, and all survivors are in New York Heart Association
      class I at follow-up ranging from 2 to 25 years. Thus, long-term survival after
      repair of APSD in early infancy is excellent. Late sequelae are likely to be
      related either to associated lesions or to obstruction at the APSD repair site.
      Almost all cases of APSD in young infants can be diagnosed and evaluated by
      echocardiography without catheterization.

PMID- 9591905
TI  - Clinical and echocardiographic outcomes of aortic intramural hemorrhage compared
      with acute aortic dissection.
AB  - Aortic intramural hemorrhage (IMH), which presents clinical manifestations
      identical to those of acute aortic dissection, is different from aortic
      dissection in terms of the absence of intimal tear and communication of blood
      flow between the true and false lumen. This study was conducted for the purpose
      of diagnosing IMH by transesophageal echocardiography (TEE) prospectively and
      comparing the clinical and echocardiographic outcome of IMH with aortic
      dissection. Between August 1991 and November 1996, 27 IMHs and 73 acute aortic
      dissections were diagnosed using TEE in 202 consecutive patients with suspected
      aortic dissections. The TEE diagnoses of IMH and aortic dissection were initially
      compared with computed tomography and magnetic resonance imaging and later
      confirmed by operative findings (n = 37) or follow-up changes (n = 12). In the 49
      patients whose diagnosis was confirmed by operation or follow-up changes, the
      sensitivity and specificity of TEE for the diagnosis of IMH were 27 of 27 (100%)
      and 20 of 22 (91%), respectively. There were 11 deaths in 73 patients (15%) from
      acute aortic dissection and 1 death in 27 patients (4%) from IMH during a follow
      up of 1.7+/-1.5 years (p = NS). Stanford classification and types of treatment
      were not related to death in both groups. Complications developed less often in
      patients with IMH (3 of 27) than in those with acute aortic dissection (24 of
      73), and no death occurred in patients with uncomplicated IMH who were medically
      treated. A follow-up imaging study of 12 IMH patients showed complete resolution
      in 8, regression in 3, and progression in 1 patient. TEE is accurate in the
      diagnosis of IMH and IMH has a lower incidence of complications than aortic
      dissection because of the absence of intimal tear and communication of blood flow
      in the false lumen.

PMID- 9591906
TI  - Thrombolysis in the management of lower limb peripheral arterial occlusion--a
      consensus document. Working Party on Thrombolysis in the Management of Limb
      Ischemia.
AB  - The aim of this paper is to develop an intercontinental consensus on the use of
      thrombolytic therapy in occlusive peripheral arterial disease affecting lower
      limbs. A working party of self-designated angiologists, hematologists,
      interventional radiologists, and vascular surgeons of Europe and North America
      convened at 4 closed meetings. All published data known to any of the
      participants was entered into discussion. The working party discussed the topics
      outlined in this paper and a first draft was prepared in segments by members of
      the working party, discussed, and further revised into an interim report. It was
      then circulated to a number of Societies for their input. A final meeting of the
      Working Party together with delegates of the Societies collaborated on the
      definitive version of the text. The Party appreciates that in many areas the
      scientific evidence is not yet available. Nevertheless, it was felt that enough
      practical and scientific data were available to establish recommendations for
      clinical practice as well as for reporting results of thrombolytic therapy, which
      could be updated as later evidence became available. The guidelines apply only to
      drugs currently available for clinical use. The data are also considered to be
      sufficiently cogent that regulatory agencies should move to approve thrombolytic
      agents for intra-arterial therapy of acute lower extremity ischemia.

PMID- 9591907
TI  - Clinical yield and cost of exercise treadmill testing to screen for coronary
      artery disease in asymptomatic adults.
AB  - Exercise treadmill testing is frequently performed to screen for coronary artery
      disease (CAD) in asymptomatic individuals; however, its clinical value is
      unclear. We examined a consecutive cohort of asymptomatic adults undergoing
      exercise treadmill testing at the Cleveland Clinic Foundation between September
      1990 and December 1993. End points included (1) identification of subjects with
      severe CAD and (2) performance of any second diagnostic study within 90 days of
      the index exercise treadmill test. Screening exercise treadmill testing was
      performed in 4,334 adults (median age 51, 89% men); only 34% had > or = 1 cardiac
      risk factor and 15% exhibited an abnormal response to exercise. A second test
      after treadmill testing was performed in 215 patients (in 110, coronary
      angiography; in 105, stress thallium scintigraphy, followed by coronary
      angiography in 16). The strongest predictor of referral for a second test was an
      ischemic ST-segment response (adjusted odds ratio [OR] 34, 95% confidence
      intervals [Cl] 24 to 47, p < 0.0001). The only clinical variable independently
      associated with referral for a second test was female gender (adjusted OR 0.35,
      95% CI 0.21 to 0.60, p <0.0001). Of the 126 patients who underwent coronary
      angiography, severe CAD was identified in only 19 individuals (10.44% of the
      original cohort, 95% CI 0.26% to 0.62%); coronary artery bypass grafting was
      performed in 14 of these patients. The estimated cost of exercise treadmill
      testing to identify 1 case of severe CAD for which surgical revascularization may
      provide a survival benefit was $39,623. The estimated cost per year of life saved
      was at least $55,274. Thus, as used in actual practice in 1 center, screening
      exercise treadmill testing has a low yield and is costly. This is perhaps in part
      because of the low-risk population that was selected and the failure to
      incorporate pretest variables, increasing probability of disease into post-test
      clinical decision making.

PMID- 9591908
TI  - Angioscopy of culprit coronary lesions in unstable angina pectoris and
      correlation of clinical presentation with plaque morphology.
AB  - This study demonstrates that plaque disruption and thrombus are absent in a
      considerable number of patients with unstable angina and that culprit lesion
      morphologies as assessed by angioscopy may differ among the various clinical
      subsets of patients. Although plaque disruption and thrombus undoubtedly play an
      important role in the pathogenesis of unstable angina, alternative mechanisms may
      be responsible for ischemia in some patients.

PMID- 9591909
TI  - Visualization of stents in the left anterior descending coronary artery by
      transthoracic echocardiography in pigs and humans.
AB  - In this study, we demonstrate that coronary artery stents can be visualized by
      transthoracic 2-dimensional echocardiography. We were able to image stents in the
      left anterior descending coronary artery in 6 of 6 pigs and in 6 of 7 patients
      studied.

PMID- 9591910
TI  - Effects of increasing doses of alpha-tocopherol in providing protection of low
      density lipoprotein from oxidation.
AB  - In this study, we tested whether 1,200 IU/day of alpha-tocopherol was more potent
      than 400 and 800 IU of alpha-tocopherol in decreasing low-density lipoprotein
      (LDL) oxidative susceptibility in a 2-month study. The decrease in LDL oxidation
      was significantly greater with 1,200 IU/day than 400 IU/day.

PMID- 9591911
TI  - Safety and feasibility of same day discharge in patients undergoing
      radiofrequency catheter ablation.
AB  - We retrospectively analyzed outcomes of radiofrequency catheter ablation in
      patients who were discharged the same day and compared them with patients staying
      overnight. For most tachyarrhythmias, it is safe and feasible to discharge
      patients undergoing radiofrequency ablation on the same day.

PMID- 9591912
TI  - Telemetry-documented, pace-terminable ventricular tachycardia in patients with
      ventricular fibrillation.
AB  - The follow-up prevalence of electrogram-confirmed spontaneous ventricular
      tachycardia with a cycle length of >280 ms (53%) exceeds the prevalence of
      ventricular fibrillation (23%) in patients whose only spontaneous arrhythmia
      before implantable cardioverter defibrillator implantation was ventricular
      fibrillation. Antitachycardia pacing therapy safely terminates most (89%) of
      these slower ventricular tachycardia episodes, recommending the use of tiered
      therapy devices and anticipatory activation of ventricular tachycardia detection
      and treatment algorithms for ventricular fibrillation patients who receive an
      implantable cardioverter defibrillator.

PMID- 9591913
TI  - Torsades de Pointes associated with intravenous haloperidol in critically ill
      patients.
AB  - In this retrospective case-control study, 8 of 223 consecutive patients (3.6%)
      treated with intravenous haloperidol developed torsades de pointes, and were
      compared with 41 patients randomly selected as controls. The likelihood of
      torsades de pointes associated with intravenous haloperidol is significantly
      greater in patients receiving > or = 35 mg over 24 hours or in those with a QTc
      interval of >500 ms, or both.

PMID- 9591915
TI  - Angiotensin-converting enzyme gene polymorphism in systemic hypertension.
AB  - We determined the angiotensin-converting enzyme (ACE) insertion/deletion genotype
      in 209 hypertensive individuals and in 100 matched normotensive controls. A
      significant association was detected between hypertension and the
      deletion/deletion (D/D) genotype of the ACE gene when the relation was adjusted
      for age, sex, and body mass index.

PMID- 9591914
TI  - Efficacy and tolerability in fully conscious patients of transvenous low-energy
      internal atrial cardioversion for atrial fibrillation.
AB  - Transvenous low-energy atrial cardioversion was performed in a series of fully
      conscious patients (30 patients with chronic atrial fibrillation and 5 patients
      with paroxysmal atrial fibrillation). The results show that internal atrial
      defibrillation is effective and tolerable in most patients.

PMID- 9591916
TI  - Effects of carvedilol on right ventricular function in chronic heart failure.
AB  - This study investigated the effects of carvedilol on right ventricular (RV)
      volume and systolic function in chronic heart failure patients. Carvedilol
      treatment resulted in a significant improvement of RV ejection fraction and
      systolic performance, which paralleled the improvement of systolic function
      demonstrated in the left ventricle.

PMID- 9591917
TI  - Blood rheology in patients with native heart valve disease and after valve
      replacement.
AB  - Patients with heart valve disease have rheologic abnormalities that are more
      pronounced in double valve disease than in mitral or aortic valve disease; after
      valve replacement surgery, the degree of rheologic abnormality is more pronounced
      in patients with mechanical and biological prostheses than in those with
      homografts and pulmonary autografts. Rheologic abnormalities seen in these
      patients might be related to the different incidences of thromboembolism in the
      presence of various valve defects and various types of prostheses.

PMID- 9591918
TI  - Usefulness of transesophageal echocardiography in determining the source of
      emboli in patients with acute limb ischemia.
AB  - A potential cardiovascular source of embolism was demonstrated by transesophageal
      echocardiography in 20 of 33 patients (61%) with acute limb ischemia. The
      percentage was higher in patients with large artery occlusions (9 of 11, 82%)
      than in those with small artery occlusions (9 of 22, 41%) (p = 0.026).

PMID- 9591919
TI  - Usefulness of isometric exercise during dobutamine administration for stress
      echocardiography.
AB  - An isometric exercise was performed by 170 consecutive patients at peak dose
      dobutamine, before atropine administration. The test was well tolerated, heart
      rate increased significantly during exercise, and atropine administration was
      avoided in 29% of patients.

PMID- 9591920
TI  - Increased incidence of myositis in patients treated with high-dose simvastatin.

PMID- 9591921
TI  - Estrogen replacement therapy and exercise performance in postmenopausal women
      with coronary artery disease.

PMID- 9591922
TI  - Innovative monotherapy trial designs for the assessment of antiepileptic drugs: a
      critical appraisal.
AB  - Although new antiepileptic drugs are assessed initially by adding them to pre
      existing treatment, it is only through monotherapy studies that their therapeutic
      potential can be characterized in full. Since long-term treatment with a placebo
      alone is ethically unacceptable in epilepsy, the classical monotherapy assessment
      of antiepileptic drugs involves randomization of newly diagnosed patients to
      treatment with the investigational drug or an established active control,
      followed by long-term monitoring to determine seizure remission rates and
      potential adverse effects. These protocols, however, are time-consuming and they
      are unlikely to demonstrate a superior efficacy of the new agent over a
      comparator. In turn, a "no-difference" outcome in terms of seizure control does
      not allow one to exclude the possibility that all the treatments were equally
      ineffective, and may therefore not be regarded as proof of efficacy by regulatory
      authorities. To circumvent these problems, innovative designs for the early
      monotherapy evaluation of new antiepileptic drugs have been developed in recent
      years. These protocols, often referred to as "regulatory trials", involve short
      term studies in which a full dosage of the investigational agent is compared with
      a placebo or with a suboptimal dosage of an active control (possibly the
      investigational agent itself). To minimize the risks associated with an
      ineffective treatment, provisions are made that require exit from the trial if
      seizures are inadequately controlled. Efficacy endpoints are time to the n(th)
      seizure and patients' retention on the allocated treatment. These studies have
      been conducted in patients undergoing discontinuation of treatment for
      presurgical assessment, in newly diagnosed patients, and in patients whose
      concomitant anticonvulsants were withdrawn for trial purposes. While these trials
      allow statistical demonstration of superior efficacy over a comparator,
      allocation of patients to ineffective or suboptimal treatments raises serious
      ethical concerns. The scientific value of these studies is also doubtful, because
      dosing schedules and duration of treatment are hardly relevant to routine
      clinical practice. Clinicians do not need to know whether a new drug given for a
      few days is better than nothing, but how that drug compares with established
      agents given in optimized dosages for long periods of time. The ethical and
      scientific justification for regulatory trials should be reassessed, and steps
      are urgently needed to stimulate implementation of long-term randomized
      comparative trials under conditions that are more relevant to clinical needs.

PMID- 9591923
TI  - Clinical and toxicological consequences of the inductive potential of ethanol.
AB  - Variability in drug metabolism is an important factor that accounts for
      individual responsiveness to xenobiotics. Enzyme induction which leads to a more
      rapid elimination of foreign compounds and to a more extensive formation of
      potentially active metabolites significantly contributes to large interindividual
      variability in drug effects. Ethanol is consumed worldwide in tremendous amounts
      and is an effective inducer of hepatic drug metabolism, especially involving
      pathways accomplished by the CYP2E1 isoform of the cytochrome P-450 (CYP)
      superfamily. Therefore, whenever xenobiotics that are substrates of CYP2E1, such
      as chlorzoxazone, paracetamol (acetaminophen), halothane, enflurane,
      methoxyflurane, sevoflurane and many organic solvents (e.g. aniline,
      trichloroethylene), are taken by an individual who is also chronically consuming
      ethanol, the accelerated metabolism of these agents and their clinical impact
      (e.g. decrease in drug activity) and toxicological impact (accumulation of active
      metabolites) have to be considered. Consequently, in the assessment of drug
      disposition and action the history of ethanol intake should be carefully
      evaluated.

PMID- 9591924
TI  - Adverse events in phase-I studies: a report in 1015 healthy volunteers.
AB  - OBJECTIVE: This report describes all clinical, laboratory and
      electrocardiographical adverse events detected in healthy volunteers in a phase-I
      centre over a 10-year period: 54 phase-I studies are involved, including 1015
      healthy young volunteers (993 males) who received 1538 treatments (23 different
      active drugs or placebo) corresponding to 12143 days of follow-up. This updates a
      similar report published previously in the European Journal of Clinical
      Pharmacology. METHODS: Adverse events were defined as all events noted in case
      report forms. Incidence of adverse events was defined as the ratio between the
      number of adverse events and the number of follow-up days. Severity was rated as
      death, life-threatening, severe or minor. Incidences or occurrence rates were
      compared using the Chi-squared test with Yates' correction. RESULTS: The overall
      incidence of adverse events was 12.8% with a significant difference between
      active-drug (13.7%) and placebo (7.9%) treatments. There were 1558 adverse events
      of 110 distinct kinds. Only for three (headache, diarrhoea and dyspepsia) was the
      incidence superior to 10 per thousand. Most of these adverse events were also
      observed with placebo. Ninety-seven percentage of adverse events were of minor
      intensity; forty three (3%) were rated as severe, including nine worrying cases -
      six malaises with loss of consciousness, one atrial fibrillation, one
      hyperthyroidism and one bicytopenia. Some of the adverse events were not related
      to the tested drugs, but to a vagal reaction or to study conditions. There was no
      death or life-threatening event. The global rate of occurrence was one adverse
      event per treatment, one and a half per subject and one out of eight follow-up
      days. No difference in the overall incidence with placebo was observed between
      the two successive 5-year periods. CONCLUSIONS: This report confirms that adverse
      events in phase I studies are very common, usually of minor intensity and rarely
      severe; even though exceptional, life-threatening adverse events are possible.
      Adverse events occurring in phase I are rarely published, leading to lack of
      information. Thus, authors invite clinical research organization (CROs) and phase
      I centres to regularly publicise at least severe adverse events; they also
      suggest that the life-threatening adverse events reported to health authorities
      should be publicised, for example by the World Health Organization (WHO).

PMID- 9591925
TI  - Effect of prostaglandin E1 on pulmonary hypertension after protamine injection
      during cardiac surgery.
AB  - BACKGROUND: The effects of prostaglandin E1 on pulmonary hypertension were
      assessed after protamine injection at the end of cardiopulmonary bypass during
      cardiac surgery. METHODS: Ten patients scheduled for cardiac surgery presented
      with pulmonary hypertension (mean pulmonary artery pressure greater than 30 mmHg)
      after protamine injection and were treated by infusion of 0.02 microg x kg(-1) x
      min(-1) prostaglandin E1. Hemodynamic measurements were made on occasions after
      cardiopulmonary bypass. Prostaglandin E1 decreased pulmonary artery pressure,
      pulmonary vascular resistance, right ventricular stroke work index and pulmonary
      vascular resistance/systemic vascular resistance ratio, but did not change blood
      pressure, systemic vascular resistance, left ventricular stroke work index or
      cardiac output. CONCLUSION: Prostaglandin E1 normalized pulmonary hypertension
      after protamine injection, but did not change arterial blood pressure and cardiac
      output.

PMID- 9591926
TI  - The efficacy of a low-dose, monodisperse parasympathicolytic aerosol compared
      with a standard aerosol from a metered-dose inhaler.
AB  - OBJECTIVE: In previous experiments we showed that monodisperse bronchodilator
      aerosols with a median mass aerodynamic diameter of 2.8 microm induced stronger
      bronchodilatations than larger aerosols and that the dilatations were clinically
      relevant at low doses. To discover whether the bronchodilator effects of these
      low-dose monodisperse aerosols differed from those of standard dosages delivered
      by metered-dose inhalers, we carried out a comparative trial. METHODS: Ten stable
      outpatients with a mean forced expiratory volume in 1 s (FEV1) of 58.1% of the
      predicted value inhaled a placebo aerosol, 8 microg of a 2.8-microm monodisperse
      ipratropium bromide aerosol and 40 microg from a metered-dose inhaler plus
      spacer; lung-function measurements followed. Data were analysed with repeated
      measurements analysis of variance (ANOVA). RESULTS: Greater improvements than
      with placebo were evident for the forced vital capacity (FVC), the FEV1, the
      specific airway conductance (sGaw), the peak flow (PEF) and the maximum
      expiratory flow at 75% of the forced vital capacity (MEF75). In these cases, the
      low-dose 2.8-microm aerosol proved to be equivalent to the higher-dose metered
      dose inhaler. CONCLUSION: By changing the polydisperse characteristic of inhaled
      aerosols to a monodisperse pattern, the dose of the drug administered can be
      reduced without loss of efficacy.

PMID- 9591927
TI  - Comparison of venodilatory effect of nicardipine, diltiazem, and verapamil in
      human subjects.
AB  - OBJECTIVE: Venodilatory effects of calcium antagonists have not been fully
      investigated, especially in human subjects. The present study was undertaken to
      compare the direct venodilatory effects of nicardipine, diltiazem and verapamil
      using the dorsal hand-vein technique. METHODS: In eight healthy male subjects,
      increasing doses (0.001, 0.01, 0.1, 1 and 10 microg x min(-1)) of these drugs and
      saline alone were infused, on four separate occasions, into the dorsal hand vein
      preconstricted with noradrenaline, and its diameter was measured by a linear
      variable differential transformer. RESULT AND CONCLUSIONS: Diltiazem caused
      significant venodilation at a dose of 0.01 microg x min(-1) or more, while
      verapamil and nicardipine only caused this effect at 1 microg x min(-1) or more.
      The potency of the effect was diltiazem > verapamil > nicardipine. The
      venodilation at a dose of 1 microg x min(-1) was 41.7%, 16.2% and 8.5%,
      respectively, for each drug. These findings indicate that the venodilatory effect
      of diltiazem is larger than that of verapamil and nicardipine in human subjects.

PMID- 9591929
TI  - Nonformulary drug requests at an academic hospital in Germany--the role of
      general practitioners' long-term medication.
AB  - OBJECTIVE: To determine the influence of general practitioners' outpatient
      medication on nonformulary drug requests in university hospitals. METHODS: During
      a period of 1 year every nonformulary drug request at the Gottingen University
      Hospital was analysed (reason for request, drug class). A second analysis
      examined whether the introduction of a new order form that allowed the
      prescribing physician to mark a box to declare that this request is due to
      general practitioner's outpatient therapy influenced the rate of requests.
      RESULTS: During 12 months a total of 6,281 nonformulary drugs were ordered from
      the pharmacy, 1,077 (17.1%) of them because of outpatient medication. The
      percentage of requests according to general practitioners' outpatient medication
      was about 11% in both the medical and the surgical departments. The rate was
      rather high in the departments of psychiatry and orthopaedic surgery (39% and
      60%, respectively). With the introduction of the new order form, there was a
      significant increase in the general practice based rate of nonformulary requests
      on the general surgical wards (from 10.8% to 19.9%). Only a minority of requests
      (14%) represented drugs of unproven efficacy. CONCLUSION: Since nonformulary
      requests attributable to previous outpatient medication accounts for less than
      20% and since only a minor portion of them lack scientific proof of efficacy we
      suggest that hospital doctors and clinical pharmacologists should avoid a drug
      policy, which is too restrictive, and support maintenance of chronic medication
      initiated by general practitioners. Especially in the department of psychiatry,
      nonformulary requests seem to be justified by patient needs.

PMID- 9591928
TI  - Dilatory effects of phosphodiesterase inhibitors on human hand veins in vivo.
AB  - OBJECTIVE: To compare the venodilator potencies of the phosphodiesterase (PDE)
      III inhibitors amrinone and enoximone with the unspecific PDE inhibitors
      theophylline and pentoxifylline in human hand veins in vivo. METHODS: Eighteen
      healthy nonsmokers (16 men and two women) were studied using the dorsal hand vein
      technique. After preconstriction with the selective alpha1-adrenergic-receptor
      agonist phenylephrine dose-response curves were constructed for amrinone (1-270
      microg x min(-1)), enoximone (1-270 microg x min(-1)), theophylline (5-1500
      microg x min(-1)) and pentoxifylline (2-877 microg x min(-1)) in a random order
      on separate occasions. Due to limitation in the maximum dose infused in order to
      avoid systemic effects, full dose-response curves could not be constructed for
      pentoxifylline. In this case, the individual dose of pentoxifylline and
      theophylline producing 50% venodilation were compared. RESULTS: All PDE
      inhibitors induced dose-dependent venodilation. The value of maximum venodilation
      was the same for amrinone, enoximone and theophylline. The infusion rate needed
      to induce 50% of maximum venodilation (ED50) was not significantly different for
      amrinone (geometric mean, 8.8 microg x min(-1)) and enoximone (14.2 microg x min(
      1)), whereas the ED50 of theophylline (84.0 microg x min(-1)) was significantly
      higher than either amrinone or enoximone. The dose necessary to dilate the vein
      to 50% the maximum dilation (as determined during sodium chloride infusion) was
      significantly higher for pentoxifylline than for theophylline (409 vs 71 microg x
      min(-1)). CONCLUSIONS: These findings demonstrate that enoximone and amrinone
      have similar venodilatory potency which is six times higher than that of
      theophylline. The least potent vasodilator in this study was pentoxifylline.

PMID- 9591930
TI  - Influence of donor and recipient genotypes on CYP2D6 phenotype after liver
      transplantation: a study of mutations CYP2D6*3 and CYP2D6*4.
AB  - OBJECTIVE: After liver transplantation (LT), genotypic differences between the
      recipient and the transplanted liver, medications and post-LT complications may
      all affect drug metabolism. We have studied the effect of two CYP2D6 mutations in
      the donor and the recipient on post-LT CYP2D6 phenotype. METHOD: The CYP2D6
      phenotype was assessed in 48 patients before and after LT with debrisoquine or
      dextromethorphan. CYP2D6*3 (CYP2D6A) and CYP2D6*4 (CYP2D6B) mutations were
      detected in the donor and the recipient using polymerase chain reaction. RESULTS:
      Before LT, 40 subjects were classified as extensive metabolisers (EM) and 8 as
      poor metabolisers (PM); after transplantation, 41 were EMs and 7 were PMs.
      Genotype and phenotype were in agreement in 100% of EMs and 40% of PMs. The low
      percentage of agreement in PMs could not be explained by severely altered liver
      function. The phenotype of 13 subjects was apparently changed by LT: 6 EMs became
      PMs and 7 PMs became EMs. All four subjects in whom genotype changed following LT
      had a corresponding change in phenotype: two EM subjects became PMs and two PM
      subjects became EMs. CONCLUSION: The low percentage of agreement in PMs may be
      partly explained by mutations other than CYP2D6*3 and CYP2D6*4. Nevertheless, our
      study shows that the CYP2D6 genotype of the donor controls the phenotype of the
      recipient of a liver transplantation.

PMID- 9591931
TI  - The area under the plasma concentration-time curve for oral midazolam is 400-fold
      larger during treatment with itraconazole than with rifampicin.
AB  - OBJECTIVE: To determine the effects of treatment with itraconazole and rifampicin
      (rifampin) on the pharmacokinetics and pharmacodynamics of oral midazolam during
      and 4 days after the end of the treatment. METHODS: Nine healthy volunteers
      received itraconazole (200 mg daily) for 4 days and, 2 weeks later, rifampicin
      (600 mg daily) for 5 days. In addition, they ingested 15 mg midazolam before the
      first treatment, 7.5 mg on the last day of itraconazole administration, and 4
      days later, and 15 mg 1 day and 4 days after the last dose of rifampicin. The
      disposition of midazolam and its alpha-hydroxy metabolite was determined and its
      pharmacodynamic effects were measured. RESULTS: During itraconazole treatment, or
      4 days after, alpha-hydroxymetabolite the dose-corrected area under the plasma
      midazolam concentration time curve (AUC0-infinity) was 8- or 2.6-fold larger than
      that before itraconazole (i.e. 1707 or 695 versus 277 ng x h x ml(-1)),
      respectively. One day after rifampicin treatment, the AUC0-infinity of midazolam
      was 2.3% (i.e. 4.4 ng x h x ml(-1)) of the before-treatment value and only 0.26%
      of its value during itraconazole treatment; 4 days after rifampicin, the AUC0
      infinity was still only 13% (i.e. 27.1 ng x h x ml(-1)) of the before-treatment
      value. The peak concentration and elimination half-life of midazolam were also
      increased by itraconazole and decreased by rifampicin. The ratio of plasma alpha
      hydroxymidazolam to midazolam was greatly decreased by itraconazole and increased
      by rifampicin. In addition, the effects of midazolam were greater during
      itraconazole and smaller 1 day after rifampicin than without treatment.
      CONCLUSION: Switching from inhibition to induction of cytochrome P450 3A (CYP3A)
      enzymes causes a very great (400-fold) change in the AUC of oral midazolam.
      During oral administration of CYP3A substrates that undergo extensive first-pass
      metabolism, similar changes in pharmacokinetics are expected to occur when potent
      inhibitors or inducers of CYP3A are added to the treatment. After cessation of
      treatment with itraconazole or rifampicin, the risk of significant interaction
      continues up to at least 4 days, probably even longer.

PMID- 9591932
TI  - Pharmacokinetics of imidapril and its active metabolite imidaprilat following
      single dose and during steady state in patients with chronic renal failure.
AB  - OBJECTIVE: An open study on the single dose and steady-state pharmacokinetics of
      imidapril, a novel prodrug-type angiotensin-converting enzyme (ACE) inhibitor,
      and its active metabolite imidaprilat was conducted in eight patients with
      moderate chronic renal failure [mean creatinine clearance (CL(CR)) 64 ml x min(
      1); range 42-77 ml x min(-1)], eight patients with severe chronic renal failure
      (mean CL(CR), 18 ml x min(-1); range 11-29 ml x min(-1)) and eight healthy
      volunteers with normal renal function. Subjects received an oral dose of 10 mg
      imidapril once per day for 7 days. RESULTS: No statistical differences of either
      maximum concentration (Cmax) or the area under the curve (AUC) were found between
      patients with moderate renal failure and healthy subjects. However, Cmax and AUC
      for both imidapril and imidaprilat were significantly higher in patients with
      severe renal impairment than in healthy volunteers. There were no clinically
      relevant differences among the three subject groups with regard to total urinary
      excretion of both imidapril and imidaprilat. CONCLUSION: The smallest imidapril
      dose which is clinically effective should be used in patients with severe renal
      insufficiency.

PMID- 9591933
TI  - Pharmacokinetics and pharmacodynamics of acetazolamide in patients with transient
      intraocular pressure elevation.
AB  - OBJECTIVE: To characterize the pharmacokinetics and pharmacodynamics of
      acetazolamide in patients with transient intraocular pressure (IOP) elevation and
      to provide individual patients with the optimal dosage regimen for this drug.
      METHODS: We studied 17 patients with transient IOP elevation, who were given 62.5
      500 mg acetazolamide orally as single or repetitive doses. Plasma acetazolamide
      concentration and IOP were measured at approximately 1, 3, 5, and 9 h after the
      last acetazolamide administration. Pharmacokinetics and pharmacodynamics were
      analyzed by nonlinear mixed-effect modeling using the program NONMEM. RESULTS:
      The plasma concentration profile of acetazolamide was characterized by a one
      compartment model with first-order absorption. The apparent oral clearance was
      related to the creatine clearance (CCR) which was estimated by the Cockcroft and
      Gault equation, as follows: 0.0468 x CCR1 x h(-1). The estimated apparent oral
      volume of distribution, first-order absorption rate constant, and absorption lag
      time were 0.231 l x kg(-1), 0.821 x h(-1), and 0.497 h, respectively. IOP after
      oral acetazolamide administration was characterized by an Emax model. The maximal
      effect in lowering the IOP (Emax) was 7.2 mmHg, and the concentration
      corresponding to 50% of the maximal effect (EC50) was 1.64 microg x ml(-1). As
      70% of Emax was achieved at a plasma concentration of 4 microg x ml(-1), this
      concentration was considered satisfactory for lowering IOP. The recommended
      dosage was calculated so that the minimum plasma concentration at steady state
      exceeded this target concentration; 250 mg t.i.d., 125 mg t.i.d., 125 mg b.i.d.,
      and 125 mg once daily for the patients with CCR values of 70, 50, 30, and 10 ml
      min(-1), respectively. CONCLUSION: Measuring plasma concentrations of
      acetazolamide and subsequent pharmacokinetic and pharmacodynamic analyses are
      useful for estimating its concentration-dependent effectiveness in lowering the
      IOP in individual patients. The dosage regimen presented in this study is
      expected to improve the benefits of acetazolamide pharmacotherapy in most elderly
      patients with transient rises in IOP following intraocular surgery.

PMID- 9591934
TI  - Detection of a drug-drug interaction on population-based phenobarbitone clearance
      using nonlinear mixed-effects modeling.
AB  - OBJECTIVE: Nonlinear mixed-effects modeling (NONMEM) was used to estimate the
      effects of drug drug interaction on phenobarbitone clearance values, using 648
      serum levels gathered during the routine clinical care of 349 pediatric and adult
      epileptic patients (age range, 0.4-33.3 years). Patients received phenobarbitone
      as monotherapy or in combination with either of the antiepileptic drugs
      carbamazepine or valproic acid. RESULTS: The final model describing
      phenobarbitone clearance was CL = 52.3 x TBW(-0.567) x CO, where CL is clearance
      (ml x kg(-1) x h(-1)), TBW is total body weight (kg) and CO is a scaling factor
      for concomitant medication with a value of 1 for patients on phenobarbitone
      monotherapy, 46.4(-1/TBW) for those patients receiving concomitant carbamazepine
      and 0.642 for those patients receiving concomitant valproic acid. Phenobarbitone
      CL was highest in the very young and decreased in a weight-related fashion in
      children, with minimal changes observed in adults. This pattern was consistent
      whether phenobarbitone was administered alone or coadministered with
      carbamazepine or valproic acid. When phenobarbitone was coadministered with
      carbamazepine or valproic acid, phenobarbitone CL decreased compared with that in
      monotherapy. Its magnitudes in the presence of carbamazepine are maximal in early
      childhood (about 54%) and decreased in a weight-related fashion in older
      children, with minimal changes observed in adults. Concomitant administration of
      phenobarbitone and valproic acid resulted in a 35.8% decrease of phenobarbitone
      CL.

PMID- 9591935
TI  - The interaction effect of grapefruit juice is maximal after the first glass.
AB  - OBJECTIVE: To compare the acute effect of grapefruit juice intake on the
      pharmacokinetics and haemodynamic effects of felodipine ER tablets with the
      interaction after 14 days intake of drug with juice. METHODS: Twelve healthy male
      volunteers were included in this cross-over trial and randomly allocated to a
      daily intake of a 10-mg felodipine extended release tablet with water or
      grapefruit juice for 14 days. The two study periods were separated by at least 14
      days. The pharmacokinetics of felodipine and dehydrofelodipine, as well as the
      haemodynamic effects of the drug, were studied during day 1 and 14 in each
      period. RESULTS: Similarly to previous single-dose studies, the treatment during
      the first day with grapefruit juice increased the AUC (+73%) and Cmax (+138%) of
      felodipine when compared with the control treatment. On day 14 a similar effect
      of grapefruit juice was observed, with an increased AUC24 (+57%) and Cmax (+114%)
      of felodipine compared with the control experiment. A significant accumulation of
      felodipine occurred during both the control (+37%) and grapefruit juice (+25%)
      period. The extent of accumulation was not significantly different in the two
      treatment periods. The pharmacokinetics of the metabolite dehydrofelodipine were
      affected to a similar extent by the juice on day 1 and day 14. The first dose of
      felodipine together with grapefruit juice was associated with a significant
      additional increase in heart rate when compared with the control therapy, whereas
      there was no additional effect on blood pressure when therapy included grapefruit
      juice. On day 14 the intake of drug with juice resulted in an additional increase
      in heart rate and reduction in diastolic blood pressure in comparison with the
      control experiment. Furthermore, the vascularly related adverse events were more
      frequent in the period including grapefruit juice. CONCLUSION: The interaction
      between grapefruit juice and felodipine appears to be already fully developed
      after the first glass of grapefruit juice, as the change in pharmacokinetics in
      comparison with the control experiment is similar on day 1 and on day 14.
      Concomitant intake of 10 mg felodipine ER and the juice is associated with
      increased haemodynamic effects in healthy subjects both after a single dose and
      following 14 days of concomitant intake.

PMID- 9591937
TI  - Rifaximin systemic absorption in patients with ulcerative colitis.

PMID- 9591936
TI  - Pharmacokinetic studies of mitoxantrone and one of its metabolites in serum and
      urine in patients with advanced breast cancer.
AB  - OBJECTIVE: Mitoxantrone (MTO) was administered to patients with advanced breast
      cancer either as free MTO (f-MTO) or liposomal MTO (1-MTO). The intra- and
      interindividual variations in serum pharmacokinetics of MTO were analysed. In
      addition, the excretion of MTO and its metabolite mitoxantrone dicarboxylic acid
      (MTOD) in urine was determined. METHODS: The concentration of MTO was measured by
      high-performance liquid chromatography in serum over a period of 24 h and the
      amount of MTO and the metabolite MTOD excreted in urine over 18 h was determined.
      Pharmacokinetic parameters of f-MTO and 1-MTO were calculated. RESULTS: 1-MTO had
      a significantly longer half-life of distribution in the deep (third) compartment
      and thus a larger area under the curve (AUC) than f-MTO. No difference was found
      with respect to distribution in the peripheral (second) compartment. The kinetics
      of MTO in serum did not significantly differ between patients. In four patients
      repeated pharmacokinetic analyses gave superimposable results. Thus, there was no
      enzyme induction during therapy. By contrast, two patients with oedema had a much
      longer mean residence time (MRT) and AUC for MTO in serum. Despite the altered
      pharmacokinetics of f-MTD and 1-MTO, no toxic adverse effects occurred in these
      two patients. CONCLUSIONS: f-MTO and 1-MTO exhibited different distribution
      patterns in the deep compartment with a significantly increased half-life for 1
      MTO. There is no need to monitor MTO for treatment of breast cancer patients with
      f-MTO. In patients with oedema, the MRT of MTO is prolonged. The clinical
      relevance of this observation is as yet unclear.

PMID- 9591938
TI  - Digitoxin intoxication during concomitant use of amiodarone.

PMID- 9591939
TI  - Excimer laser for various degrees of myopia. A new model estimating the immediate
      response, the regression, the final response and the time relationship.
AB  - PURPOSE: To demonstrate a unified model for various degrees of myopia,
      characterizing the response-time relationship and its influence of topical
      corticosteroids. METHODS: 84 eyes were treated with excimer laser for myopia
      (median -7.1 D). 50 eyes received topical NSAID for 4 days (group 1), and 34 eyes
      (group 2) were further treated postoperatively with bandage lens and topical
      corticosteroids for three months. The response-time relationship was expressed as
      P(t)=a+b*exp(k*t), where P(t) is the response expressed as the percent change in
      dioptric power to the postoperative time t, a is the final percent response, b is
      the total percent regression and k the time constant. a+b express the percent
      immediate response and T1/2=0.69/k denote the time within which half of the total
      regression has occurred. RESULTS: The immediate and final responses were
      significantly larger in group 2 (128.9% and 70.5%) compared with group 1 (110.5%
      and 59.8%). T1/2 was significantly longer in group 2 (2.1 month) compared with
      group 1 (0.8 month) CONCLUSION: Use of bandage lens together with steroids
      significantly influences the response-time relationship after excimer laser
      treatment for myopia.

PMID- 9591941
TI  - Toxic effect of rose bengal dye on the living human corneal epithelium.
AB  - PURPOSE: To investigate whether rose bengal dye at a concentration of 1% has a
      toxic in vivo effect on the human corneal epithelium. MATERIAL AND METHODS: 80
      patients with presumed keratoconjunctivitis sicca (KCS) were examined with break
      up time, Schirmer 1 test, and staining with fluorescein sodium and rose bengal.
      The corneal surface was observed in the slit lamp and photographed by means of
      non-contact photomicrography. RESULTS: After the application of rose bengal 1% in
      eyes preinstilled with fluorescein sodium 1% myriads of green dots appeared on
      the corneal surface in all 32 patients with KCS according to Copenhagen criteria,
      in 17/18 with low Schirmer 1 test values only, and in 21 of the remaining 30 in
      whom the KCS diagnosis wasn't verified. CONCLUSIONS: The appearance of green
      microdots after the application of rose bengal was probably due to the
      interruption of intercellular junctions and the penetration of fluorescein
      stained fluid below the superficial cells. Whether this phenomenon reveals an
      unhealthy corneal surface and thus has a clinical significance has to be further
      investigated.

PMID- 9591940
TI  - Paired arcuate keratotomy for congenital and post-keratoplasty astigmatism.
AB  - PURPOSE: To study the effect of arcuate keratotomy on corneal astigmatism in
      previously grafted eyes compared to eyes with naturally occurring astigmatism.
      SUBJECTS AND METHODS: Twenty-three eyes with naturally occurring astigmatism and
      21 eyes with post-keratoplasty astigmatism were treated by arcuate keratotomies
      in the steepest corneal meridian. Visual acuity, spherically equivalent
      refraction, and refractive cylinder were measured before surgery and 1 to 10
      years after the operation. RESULTS: The preoperative refractive cylinder was
      reduced from 5.0 dioptres (median) to 1.25 dioptres in eyes with natural
      astigmatism and from 7.0 dioptres to 3.25 dioptres in post-keratoplasty eyes.
      Spherical equivalent refraction changed from -0.6 dioptres to -1.5 dioptres in
      eyes with natural astigmatism and from -3.5 dioptres to -4.5 dioptres in
      previously grafted eyes. The induced change in astigmatism, as calculated by
      Fourier analysis, correlated strongly with the existing preoperative astigmatism.
      The effect of the procedure did not correlate with the type of astigmatism
      (congenital vs. post-keratoplasty), time after surgery, or with patient age or
      sex. CONCLUSION: Arcuate keratotomy is a simple procedure to reduce naturally
      occurring astigmatism as well as induced astigmatism after keratoplasty. Parallel
      to the astigmatic change, negligible changes in the spherical equivalent are
      induced.

PMID- 9591942
TI  - Presence and distribution of hyaluronan in human corneas after phototherapeutic
      keratectomy.
AB  - PURPOSE: To evaluate the reactive hyaluronan (HA) formation in the human cornea
      following excimer laser surgery. METHODS: Fourteen patients underwent
      phototherapeutic keratectomy in order to remove corneal opacifications caused by
      a range of diseases. A penetrating corneal transplantation was performed between
      6 and 44 months later because of unsatisfactory visual outcome. The corneal
      buttons were fixed in 4% formaldehyde containing 1% cetylpyridine chloride. The
      histological sections were stained for the presence of hyaluronan. RESULTS:
      Hyaluronan was found in the subepithelial region of the ablated area in thirteen
      out of fourteen human corneal specimens It was present as long as 44 months after
      surgery and it is found despite of topical steroid treatment postoperatively.
      CONCLUSION: The human cornea commonly reacts to excimer laser surgery by the
      formation of hyaluronan.

PMID- 9591943
TI  - Corneal epithelium and UV-protection of the eye.
AB  - PURPOSE: To study UV-absorption and UV-induced fluorescence in the bovine corneal
      epithelium. METHODS: Spectrophotometry and spectrofluorimetry. RESULTS: The
      corneal epithelium absorbs UV-B radiation mainly owing to its content of protein,
      RNA, and ascorbate. Some of the absorbed energy is transformed to the less
      biotoxic UV-A radiation by fluorescence. RNA and ascorbate reduce tissue
      fluorescence. CONCLUSIONS: The corneal epithelium acts as a UV-filter, protecting
      internal eye structures through three different mechanisms: (1) Absorption of UV
      B roughly below 310 nm wavelength. (2) Fluorescence-mediated ray transformation
      to longer wavelengths. (3) Fluorescence reduction. The extremely high ascorbate
      concentration in the corneal epithelium has a key role in two of these processes.

PMID- 9591945
TI  - Comparison of different keratometers with the EyeSys videokeratoscope.
AB  - We compared the accuracy and the reproducibility of the measurements using a Haag
      Streit, a Shin-Nippon, and a Carl Zeiss keratometer and an EyeSys
      videokeratoscope. Two investigators performed 20 measurements on 3 calibrated
      steel balls and 5 measurements on 22 normal corneas with all instruments.
      Calculating the accuracy of the measurements the limits of the 95% confidence
      intervals of the bias were determined. The accuracy was better than +/-0.1D for
      the keratometers, whereas it was better than +/-0.25D for the EyeSys
      videokeratoscope. The coefficient of reproducibility (1.96 x standard deviation)
      on test balls and corneas was smaller than 0.25D in the case of the Shin-Nippon
      and Carl Zeiss keratometers and the EyeSys videokeratoscope whereas it was
      between 0.25-0.5D in the case of the Haag-Streit keratometer. The Carl Zeiss
      keratometer was the best with respect to the accuracy and reproducibility of the
      measurements. Paired t-test was used to find possible significant differences
      between the results of the two investigators, but only clinically insignificant
      differences were found.

PMID- 9591944
TI  - Light microscopic evaluation of human donor corneal stroma during organ culture.
AB  - PURPOSE: To try to facilitate evaluation of corneal stroma during organ culture
      by means of light microscopy. METHODS: Corneal stroma of 53 consecutive organ
      cultured corneas was studied by means of light microscopy during endothelial
      quality control. Out of 9 corneas with bad stromal evaluation, 2 were studied by
      means of transmission electron microscopy, and 7 were grafted. From the remaining
      44 corneas with a normal light microscopic appearance, 35 were grafted. RESULTS:
      Stromal abnormalities consisted of bright visible structures with a cell-like
      shape corresponding to keratocyte injuries (i.e. cellular edema, light and dark
      vacuoles, cell membrane disruption and, finally, internal cytolysis) as observed
      by TEM. At 3 months postoperatively no clinical differences between the two
      groups of transplants were observed. CONCLUSION: Corneal stroma can be evaluated
      qualitatively and easily by means of light microscopy during organ culture.
      Further studies are needed to investigate whether the presence of lysed
      keratocytes in the graft's stroma actually influences the outcome of
      transplantation.

PMID- 9591946
TI  - Evaluation of a new threshold visual field strategy, SITA, in normal subjects.
      Swedish Interactive Thresholding Algorithm.
AB  - PURPOSE: We developed a new family of test algorithms. This is an evaluation in
      normal subjects. METHODS: One eye in each of twenty normal subjects, with a mean
      age of 37 years (range 26 to 59), was tested twice with each of the SITA, Full
      Threshold and Fastpac strategies of the Humphrey perimeter at 3 separate visits.
      Actual test times and number of stimulus exposures were compared. Test-retest
      variability and levels of threshold estimates were also calculated and compared
      between strategies. RESULTS: In all subjects test times were shortest with SITA,
      6.14 minutes in average, which was 50% as compared to Full Threshold (p<0.001)
      with an average of 12.27 minutes, and a reduction of 16% as compared to Fastpac
      (mean 7.28 minutes, p<0.0001). SITA required 287 stimulus exposures on the
      average, significantly fewer (p<0.0001) than corresponding numbers with Full
      Threshold (mean of 404), and significantly more (p<0.0001) than with Fastpac
      (average 240). SITA results showed significantly lower test-retest variability
      than results obtained with Fastpac (p=0.0002), and just as low as those of the
      Full Threshold strategy (p=0.0979). Threshold values obtained with SITA were
      slightly higher than those produced by the other two strategies. CONCLUSIONS: The
      results confirm those of previously reported simulated tests, that improved test
      algorithms using advanced visual field models and mathematical analyses performed
      in real time may effectively shorten computerized perimetry tests, while
      achieving the same or better test quality than today's standard methods.

PMID- 9591947
TI  - Age, gender, IOP, refraction and optic disc topography in normal eyes. A cross
      sectional study using raster and scanning laser tomography.
AB  - PURPOSE: To study the influence of age, gender, intraocular pressure and
      refraction on optic disc topography in normal subjects. METHODS: We studied both
      eyes of 225 healthy subjects between 20 and 80 years of age using raster
      tomography (Glaucoma-Scope, Ophthalmic Imaging Systems, Sacramento CA, USA) and
      scanning laser tomography (Heidelberg Engineering, Heidelberg, Germany). We chose
      to study cup area and maximum cup depth, two variables that are minimally
      influenced by the operator. RESULTS: Raster and scanning laser tomography results
      were strongly correlated. Cup area was independent of age, gender and refraction.
      It was weakly associated with IOP, but this association was significant only when
      the cup area was measured with scanning laser tomography. Maximum cup depth was
      independent of age, gender and IOP. It was larger in hypermetropic eyes, although
      this trend was significant only when maximum cup depth was measured with raster
      tomography. CONCLUSION: Our results indicate that optic nerve head topography
      does not change significantly with age in normal subjects. This information has
      important implications for follow-up of pathological changes in optic nerve head
      topography.

PMID- 9591948
TI  - Tear functions in patients with pterygium.
AB  - PURPOSE: In the etiology of pterygium abnormalities in tear functions have also
      been emphasized. In this study, tear function tests are evaluated in patients
      with pterygium. METHODS: Schirmer's test 1, tear film break-up time and mucus
      fern patterns were evaluated in 70 eyes with pterygium and in 70 eyes of the age
      matched control group. Marginal tear films were also assessed. RESULTS: Tear film
      break-up time was significantly reduced in the pterygium group. Mucus fern
      patterns and marginal tear films were found to be markedly abnormal in the eyes
      with pterygium, however, there was no significant difference in Schirmer's test
      1. CONCLUSION: Tear function tests disclosed disrupted tear film stability which
      is more likely to be due to the altered mucin. This change may either be the
      primary factor inducing pterygium formation or reflect an existing pathology in
      the cells lining the ocular surface.

PMID- 9591949
TI  - Antibiotics in irrigation solution for cataract surgery. A laboratory
      investigation of the pharmacological stability and bacteriological
      susceptibility.
AB  - PURPOSE: To evaluate the appropriateness of a prophylactic use of Gentamicin and
      Vancomycin in the irrigation solution for cataract surgery. METHODS: A laboratory
      study of the pharmacological stability and the bacteriological susceptibility of
      the two antibiotics and epinephrine in the irrigation solution. RESULTS:
      Gentamicin and Vancomycin are pharmacologically stable in concentrations above
      the MIC-values of most Gram positive and Gram negative bacteria without reaching
      toxic levels. CONCLUSION: Although it seems tempting to add Gentamicin and
      Vancomycin in irrigation solutions for cataract surgery, major objections to such
      a prophylactic use of antibiotics have been stated, specially focusing on the
      risk of emerging resistance to the antibiotics, and the financial implications.

PMID- 9591950
TI  - Lens epithelial growth on the anterior surface of hydrogel IOLs. An in vivo
      study.
AB  - PURPOSE: Descriptive study designed to investigate the cellular event occurring
      on the anterior surface of a hydrogel intraocular lens (IOL), Hydroview model
      H60M over 3 years following implantation. METHODS: Slitlamp photos and specular
      microscopy were performed on 25 subjects at specified intervals following
      implantation in order to document the morphology and extent of the cellular
      reaction on the anterior surface of the IOLs. A laser flare meter was used to
      evaluate the post-op inflammation. RESULTS: In 13 of the 25 cases proliferation
      of lens epithelial cells (LECs) was detected on the anterior surface at various
      levels of severity.

PMID- 9591951
TI  - Fluorescein angiography of the iris in the management of eyes with central
      retinal vein occlusion.
AB  - PURPOSE: To study fluorescein angiography of the iris as a means of identifying
      eyes at risk for developing secondary glaucoma after central retinal vein
      occlusion. METHODS: Fluorescein angiography of the iris was performed with a
      scanning laser ophthalmoscope in 27 patients (27 eyes). Individual images were by
      computer, determining relative areas of fluorescein staining and leakage.
      RESULTS: The best predictor of secondary glaucoma was the relative area showing
      staining. Neither relative area of leakage nor presence of iris rubeosis, age, or
      initial visual acuity were effective means of predicting which eyes would develop
      secondary glaucoma. This occurred in six eyes; all were treated with argon laser
      photocoagulation. No eye was enucleated. CONCLUSION: Iris angiography can
      identify eyes at risk for secondary glaucoma but specificity is poor. The often
      recommended regime to perform laser photocoagulation in all eyes with iris
      neovascularisations was challenged.

PMID- 9591952
TI  - In vitro effectiveness of silicone oil removal.
AB  - PURPOSE: To evaluate the effectiveness of silicone oil removal from the human eye
      under in vitro conditions. METHODS: Six keratoplasty donor eyes were
      vitrectomized and filled with silicone oil (5000 centistokes). After oil removal,
      the amount of residual oil was determined by quantifying the silicon content of
      the eyes. Six control eyes were prepared without oil filling. RESULTS: The six
      control specimens showed a silicon content of 2.83-10.2 microg (mean 5.06 microg,
      SD 3.19), the six test specimens a silicon content of 70.54-297.10 microg (mean
      163.91 microg, SD 86.89). The difference is significant (p<0.05). The amount of
      residual oil in the test eyes was 192.0-856.2 microg (0.0037-0.0179% of the
      applicated oil quantity). CONCLUSION: The low magnitude of residual intraocular
      oil after oil removal shows that silicone oil could be removed to almost 100%
      when emulsification and biological mechanisms of oil retention are excluded. This
      could favour early silicone oil removal.

PMID- 9591953
TI  - Autosomal recessive cornea plana. A clinical and genetic study of 78 cases in
      Finland.
AB  - PURPOSE: To review the literature of autosomal recessive cornea plana (RCP) and
      to perform a clinical and genetic study on this disorder in Finland. The 78
      Finnish RCP patients represent the majority of RCP cases worldwide; outside
      Finland only 35 cases have been reported. METHODS: Families with RCP,
      particularly in northern Finland, have been followed up by the senior author
      since the 1950s and extensive genealogical studies have been made. RESULTS: The
      most typical symptoms are greatly reduced corneal refraction, 25-35 dioptres,
      causing strong hyperopia, slight microcornea, an extended limbus zone, a central,
      deep corneal opacity and a marked arcus senilis, seen even before the age of 20.
      We present a pedigree comprising 33 affected persons with cornea plana. We have
      mapped the two genes for the dominantly and the recessively inherited type of
      cornea plana to the same region on the long arm of chromosome 12, (12q21).
      CONCLUSIONS: In northern Finland RCP has a higher frequency than elsewhere,
      probably as a result of a strong founder effect in the population that arrived in
      these regions approx. 400 years ago. The strong accumulation of this rare disease
      in these isolated areas and the strong genealogical connections between different
      families with RCP, suggest that probably all the Finnish RCP cases are caused by
      the same mutation.

PMID- 9591954
TI  - Neonatal risk factors for retinopathy of prematurity--a population-based study.
AB  - PURPOSE: The aim of the study was to evaluate possible neonatal risk factors for
      retinopathy of prematurity (ROP) in a population-based group of preterm, very low
      birth weight, infants. METHOD: The main study group included 202 single-born
      infants with a birth weight of 1500 grams or less. A group of 57 twins were also
      described. Selected risk factors were extracted from the neonatal records.
      RESULTS: Univariate analysis revealed an association between ROP and respiratory
      distress syndrome (RDS), bronchopulmonary dysplasia (BPD), septicaemia,
      intraventricular bleeding, and the use of ventilator as well as continuous
      positive airway pressure. In a stepwise logistic regression analysis, however,
      only gestational age at birth, birth weight and BPD were significantly associated
      with ROP. CONCLUSION: Prematurity per se remains the strongest risk factor for
      ROP.

PMID- 9591955
TI  - Preoperative features of patients with exfoliation glaucoma and primary open
      angle glaucoma. The AHEPA study.
AB  - PURPOSE: To describe and compare the preoperative characteristics of Greek
      patients with exfoliation glaucoma (EXG) and primary open-angle glaucoma (POAG).
      METHODS: We prospectively investigated the preoperative features of 100
      consecutive patients undergoing filtration surgery for either EXG, or POAG. We
      compared 74 patients with EXG and 26 with POAG. RESULTS: EXG patients were older
      (68.2 vs 62.4 years; p<0.05) and more often from the countryside (73%). Both
      glaucomas showed a preponderance for males, similar frequencies of positive
      family history and systemic disorders, with the exception of diabetes which was
      more common in POAG (19.2% vs 5.4%). The first IOP measurement, before treatment,
      was significantly higher in EXG (40.4 mm Hg) compared with POAG (33.9 mm Hg).
      Despite a shorter duration of medical therapy (25 vs 65 months) and more topical
      drugs EXG patients exhibited higher mean preoperative IOP (36 vs 27.8 mm Hg for
      POAG; p<0.05). EXG patients had significantly worse visual acuity than POAG (0.4
      vs 0.6; p<0.05) and worse compliance to medical therapy (48%) compared to POAG
      (33%). CONCLUSION: Significant differences in preoperative features distinguish
      EXG from POAG.

PMID- 9591956
TI  - Outcome of Molteno implantation surgery in refractory glaucoma and the effect of
      total and partial tube ligation on the success rate.
AB  - PURPOSE: To analyze the results of 87 consecutive one-stage Molteno implantations
      in 87 patients and evaluate the factors influencing the surgical outcome,
      especially the effect of intraoperative partial and total occlusion of the tube.
      METHODS: Successful outcome was defined as final intraocular pressure (IOP)
      between 6 and 22 mmHg with less or equal amount of glaucoma medication than
      preoperatively without loss of light perception. RESULTS: After a mean (+/-SD)
      follow-up of 24+/-17 months, the mean IOP was 18.1+/-16.0 mmHg compared to the
      preoperative mean of 42.4+/-11.1 mmHg (p<.0001). One-, 2- and 4.5-year life-table
      success rates were 90%, 75% and 50%, respectively. There was no statistically
      significant difference in the success rate between the eyes with total and
      partial tube occlusion (p=0.703). Postoperative hyphema, suprachoroidal
      hemorrhage and the number of systemic medications were the only factors
      significantly associated with failure. CONCLUSIONS: Molteno implantation is
      warranted in patients with refractory glaucoma who have undergone numerous
      previous surgical procedures.

PMID- 9591957
TI  - Tackling the "dropped nucleus".
AB  - PURPOSE: To summarize and analyse the results of our experience in treating
      patients with a "dropped nucleus". METHODS: The case records of nineteen patients
      who underwent surgery for a "dropped nucleus" at the Ophthalmology Departments of
      Sahlgren's University Hospital, Gothenburg, and Orebro Medical Centre, Orebro,
      Sweden during 1994 were retrospectively reviewed to determine the mode of
      treatment used and the results of surgery. The frequency of this complication was
      also calculated for Sweden as a whole with the help of the National Cataract
      Register. RESULTS: The lens was successfully removed in all eyes. No retinal
      breaks or detachments were present at vitrectomy or follow-up. One eye was lost
      to panophthalmitis 11 days after the vitrectomy; the remaining 18 eyes showed a
      favourable outcome. CONCLUSION: The loss of a crystalline lens to the vitreous
      during cataract surgery is a severe complication. We recommend that an
      experienced vitreoretinal surgeon should be consulted at an early stage.

PMID- 9591958
TI  - Six-year supplementation with alpha-tocopherol and beta-carotene and age-related
      maculopathy.
AB  - PURPOSE: Animal research and observational studies in man suggest a protective
      effect of antioxidant vitamins in the development of age-related maculopathy
      (ARM). METHODS: The ATBC study, a population-based, controlled clinical trial of
      alpha-tocopherol and beta carotene to prevent lung cancer, took place in Finland
      between 1984 and 1993. Over 29,000 smoking males aged 50 to 69 years were
      randomly assigned to alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20
      mg/day), both of these, or placebo. We performed an end-of-trial ophthalmological
      examination on a random sample of 941 participants aged 65 years or more from two
      of the fourteen study areas, to discover if the five to eight-year intervention
      with alpha-tocopherol and/or beta-carotene had been associated with a difference
      in ARM prevalence. Age-related maculopathy was assessed using colour photographs
      of the macula. RESULTS: Altogether, 269 cases of ARM were found; there were more
      cases in the AT group (32%; 75/237), BC group (29%; 68/234), and combined
      antioxidant group (28%; 73/257) than in the placebo group (25%; 53/213). However,
      neither substance was significantly associated with the risk of ARM in a logistic
      regression analysis controlling for possible risk factors. CONCLUSIONS: No
      beneficial effect of long-term supplementation with alpha-tocopherol or beta
      carotene on the occurrence of ARM was detected among smoking males.

PMID- 9591959
TI  - Steady-state PVECP is superior to transient PVECP in the diagnosis of optic
      neuritis.
AB  - PURPOSE: To compare the diagnostic value for optic neuritis between transient
      pattern visual evoked potentials (PVECP) and steady-state PVECP. SUBJECTS &
      METHODS: We retrospectively studied 86 eyes of 69 patients with optic neuritis
      who visited our clinic. PVECPs to 3 rev/sec stimulation (transient) and 12
      rev/sec stimulation (steady-state), were recorded in all patients. RESULTS: All
      of the cases with non-recordable transient PVECP showed non recordable steady
      state PVECP Conversely, the cases with non-recordable steady-state PVECP often
      showed measurable transient PVECP where the latency of the P100 component was
      delayed. In 51 cases with unilateral optic neuritis, the amplitude ratio of the
      P100; affected eye/non-affected eye was significantly smaller in the steady-state
      PVECP than in the transient PVECP CONCLUSION: To detect visual dysfunction in
      optic neuritis, a steady-state PVECP was more sensitive than a transient PVECP.

PMID- 9591960
TI  - Effect of debridement of the retinal pigment epithelium in full-thickness macular
      hole surgery.
AB  - We assessed the efficacy of debridement of the retinal pigment epithelium (RPE)
      from the base of the macular hole during vitrectomy to treat 83 eyes of 75
      patients with a stage 2 (n=29), stage 3 (n=35) or stage 4 (n=19) macular hole.
      Patients ranged in age from 51 to 77 years (mean, 67.6 years). Duration of
      symptoms preoperatively ranged from 1 to 120 months (average, 19.2 months).
      During vitrectomy for macular hole, the RPE at the base of the hole was gently
      aspirated with either a silicone-tipped extrusion needle or a blunt-tipped 27
      gauge needle. Follow-up averaged 13.0 months (range, 3 to 36 months). The holes
      resolved in 73 (88%) of the 83 eyes after one surgical procedure. In 73 eyes with
      a follow-up period of 6 months or more, sixty-five (89%) showed improved VA of at
      least two lines of Snellen equivalent. Fifty-five (75%) eyes had a visual acuity
      (VA) of > or = 20/40. Our preliminary results suggest that RPE debridement from
      the base of the hole is a useful adjunct to vitrectomy for treating full
      thickness macular holes.

PMID- 9591961
TI  - Diabetic cataract in children.
AB  - PURPOSE AND METHODS: Adolescent patients with insulin-dependent diabetes mellitus
      (IDDM) were retrospectively analyzed for the occurrence and possible predisposing
      factors of diabetic cataract in a population-based series of some 600 pediatric
      diabetics followed up during the years 1975-1995. RESULTS: Six patients (1%)
      needed cataract surgery. At the diagnosis of cataract they were 9.1-17.5 years
      old, and the duration of diabetes was between 0 months and 3 years 11 months. The
      type of cataract was similar in all patients characterized by bilateral snowflake
      type cortical deposits and posterior subcapsular cataract. Four of the six
      patients had at least a six-month history of diabetic symptoms before the
      treatment was started, and five patients had ketoacidosis at initial admission to
      hospital. In one of the 11 operated eyes diabetic retinopathy was observed
      immediately after surgery. Three patients developed proliferative retinopathy
      within 7-10 months after the operation, after 6.3-11.8 years of diabetes.
      CONCLUSIONS: The prevalence of diabetic cataract was around 1% in the pediatric
      diabetic population. In the pathogenesis of cataract long duration of diabetic
      symptoms and ketoacidosis prior to the commencement of treatment may be of
      significance. Good metabolic control after diagnosis did not protect for
      cataract. Diabetic cataract can safely be treated by modern surgical techniques,
      but close monitoring of the fundi for retinopathy after the operation is crucial,
      as proliferative retinopathy may develop rapidly after cataract surgery despite
      relatively short duration and acceptable metabolic control of diabetes.

PMID- 9591962
TI  - Lacrimal sac plugging caused by Aspergillus fumigatus.
AB  - Aspergillus fumigatus is a rare cause of canalicular obstruction. We present a
      case where an aspergillosis plug caused extreme tenderness, epiphoria and
      discharge from the lacrimal puntum. CT scan showed dilation of the lacrimal sac.
      Medical treatment did not relieve the symptoms. During a planned DCR the sac was
      opened before the osteotomy, and found to contain a plug which caused the
      obstruction. Aspergillus fumigatus was grown from culture. The DCR was abandoned
      and the patient is symptom free one year after the procedure.

PMID- 9591963
TI  - Fuchs' heterochromic uveitis associated with retinitis pigmentosa.
AB  - We report a case of bilateral retinitis pigmentosa simplex (RP) with a
      combination of unilateral Fuchs' heterochromic uveitis (FHU). Both of these
      entities are quite rare syndromes and coexistence of these entities in one
      patient is rarer than can be expected. Even though this rare coexistence came
      together in one patient, we found no hereditary factors to presume that both
      traits segregate independently.

PMID- 9591964
TI  - Cyclic presentation of central macular oedema.
AB  - We present the case of a young lady with unilateral pars planitis and associated
      cystoid macular oedema in whom visual symptoms fluctuated regularly during
      successive menstrual cycles. To date no such presentation of central macular
      oedema has been reported in the literature.

PMID- 9591965
TI  - Contusion [correction of Confusion] and lens subluxation.

PMID- 9591966
TI  - Sundelin & Norsell: enlargement of extraocular muscles during treatment with
      amiodarone. Acta Ophthalmol Scand 1997: 75: 333-334.

PMID- 9591967
TI  - Development of retinal transplants.

PMID- 9591968
TI  - Controversial issues in spinal deformity surgery.

PMID- 9591970
TI  - Scoliosis in patients treated with growth hormone.
AB  - Two hundred fifty children being treated with growth hormone were screened for
      scoliosis by using the Adams and Bunnell techniques. If indicated, an
      anteroposterior radiograph was done and measured by the Cobb and Risser methods.
      Scoliosis was defined as a frontal curve of > or = 10 degrees; progression, as a
      sustained increase of > or = 5 degrees, and a progressive curve as one > or = 25
      degrees and meeting our criteria for orthotic management. In 10 of the 250
      patients, scoliosis developed. Six curves were double major thoracic and lumbar;
      three thoraco-lumbar; and one single thoracic. Six of the 10 patients had
      progressive curves and required an orthosis. Their average annualized rate of
      progression was 26 degrees. Progression was associated with double major curves
      and an earlier Risser stage. Despite bracing, progression continued to fusion in
      three patients. We conclude that growth hormone may increase the risk of
      progression of scoliosis. Furthermore, the progression is frequently rapid and
      requires special vigilance by the treating physician.

PMID- 9591969
TI  - Nighttime bracing for adolescent idiopathic scoliosis with the Charleston Bending
      Brace: long-term follow-up.
AB  - We report long-term experience with the Charleston Bending Brace for treatment of
      adolescent idiopathic scoliosis. This brace holds the patient in maximal side
      bending correction and is worn at nighttime only. Patients included in this
      prospective multicenter study met all of the following criteria: skeletal
      immaturity (Risser 0, 1, or 2), curvature >25 degrees before bracing, no prior
      treatment, and >1-year follow-up since completion of bracing (skeletal maturity
      or progression to surgery). All curves were monitored and reported. There were
      149 structural curves in 98 patients. Sixty-five (66%) patients showed
      improvement or <5 degrees change in curvature. Seventeen (17%) patients
      progressed to the point of requiring surgery for their scoliosis. Based on these
      long-term results and improvement of the natural history of adolescent idiopathic
      scoliosis, continued use of the Charleston Bending Brace is justified.

PMID- 9591971
TI  - Long-term psychosocial characteristics of patients treated for idiopathic
      scoliosis.
AB  - Psychosocial characteristics of 95 female patients treated with Milwaukee bracing
      for idiopathic scoliosis were examined using a battery of five psychosocial
      scales. Sixty-five patients treated with bracing alone and 30 patients who also
      underwent arthrodesis for curve progression were compared with 49 age-matched
      female controls. At an average follow-up of 7 years, no differences in depression
      or health locus of control existed. Significant perceptions of discrimination and
      a lower satisfaction of overall appearance was recalled during the treatment
      phase. By final follow-up, there was no longer any difference between the
      patients and controls in these areas. Significantly, differences in body-image
      scores persisted at follow-up. Operative patients had a more negative body image
      of the axial skeleton in comparison with the braced and control groups. We
      conclude that transient psychological effects are often present during treatment,
      and a lower body image may persist for several years in surgical patients.

PMID- 9591972
TI  - Curve progression in Risser stage 0 or 1 patients after posterior spinal fusion
      for idiopathic scoliosis.
AB  - A retrospective review was performed to determine "crankshaft" prevalence in 86
      immature patients who underwent posterior spinal fusion for idiopathic scoliosis.
      Tanner stage, chronologic age, bone age, and epiphyseal status were used as
      maturity indicators. Overall, 62 (72%) patients progressed < or = 10 degrees, 18
      (21%) patients progressed 11-15 degrees, and six (7%) patients progressed > or =
      16 degrees in the coronal plane. Tanner I patients with open triradiate cartilage
      had the highest rate of crankshaft occurrence; nine (75%) of 12 patients
      progressed >10 degrees (p < 0.05). Fifty-two percent of Tanner I, 26% of Tanner
      II, 11% of Tanner III, and no Tanner IV patients progressed >10 degrees (p <
      0.05). Cobb angle increases of >10 degrees degrees occurred in 54% of patients
      with open triradiate cartilage (p < 0.05) and in 48% of patients with open
      capital femoral epiphyses (p < 0.05). Anterior and posterior spinal fusion should
      be considered in prepubertal (Tanner I) patients with open triradiate cartilage.

PMID- 9591973
TI  - Prevention of fixed, angular kyphosis in achondroplasia.
AB  - Transient kyphotic deformity arises in most infants with achondroplasia. In a
      minority, a fixed and angular kyphosis develops, which can cause serious
      neurologic sequelae later in life. We assessed a protocol for preventing
      development of such fixed kyphosis in a sequential, unselected series of 66
      infants with achondroplasia. This study demonstrates the efficacy of early
      prohibition of unsupported sitting and, in those in whom such prohibition proves
      insufficient, use of bracing. When the proposed algorithm was followed, none of
      the infants had development of a progressive kyphotic deformity. On this basis,
      it appears that the secondary risks of angular kyphosis, previously estimated to
      be between 10 and 15% in individuals with achondroplasia, can be completely
      eliminated.

PMID- 9591974
TI  - Spinal instrumentation without fusion for progressive scoliosis in young
      children.
AB  - Between 1973 and 1993, a heterogeneous group of 67 children with progressive
      scoliosis entered a program of incremental-distraction spinal instrumentation
      without fusion supplemented by full-time external orthotic support. Over the
      course of treatment, curve magnitude improved from an average of 67 degrees at
      initial instrumentation to 47 degrees at definitive fusion. For all patients,
      curve response tended to decline with consecutive procedures. The measured growth
      of the instrumented but unfused spinal segments averaged 3.1 cm over a mean
      treatment period of 3.1 years. The results of our study suggest that spinal
      instrumentation without fusion can control progressive scoliosis in a majority of
      children while allowing normalized growth of instrumented spinal segments. The
      mean duration of treatment and ultimate gain in spinal length are constrained by
      progressive structural changes that alter curve response to incremental
      distraction. Despite these limitations, spinal instrumentation without fusion may
      provide a reasonable management alternative when individualized among these
      difficult patients.

PMID- 9591976
TI  - Spinal instrumentation for Duchenne's muscular dystrophy: experience of
      hypotensive anaesthesia to minimise blood loss.
AB  - Nineteen patients with Duchenne's muscular dystrophy underwent segmental spinal
      instrumentation and posterior fusion between 1989 and 1994. The indication for
      surgery was loss of the ability to walk and development of scoliosis with sitting
      discomfort. Preoperative assessment included evaluation of pulmonary function.
      Average age at operation was 12.5 years. Instrumentation and fusion extended from
      upper thoracic levels to L-5 or the sacrum. A Hartshill rectangle was used in all
      cases, with banked allograft bone. Severe intraoperative blood loss was avoided
      by use of hypotensive anaesthesia. Peroperatively, systolic blood pressure was
      maintained between 75 and 85 mm Hg. Average blood loss was 1,246 ml (range, 400
      3,100) or 30% of estimated total blood volume. Average transfusion requirements
      were 3 units of packed cells. Postoperative analgesia was provided by infusion
      via an epidural catheter. There were no postoperative wound or chest infections.
      Three patients required catheterisation for urinary retention. Postoperatively
      patients were fitted with a Neofract jacket to allow early mobilisation and
      discharge. Mean postoperative length of stay was 16 days. Posterior spinal fusion
      by using the Hartshill rectangle provided good correction and fixation.
      Hypotensive anaesthesia permitted surgery to be performed rapidly in a relatively
      dry field and avoided the complications of severe intraoperative blood loss and
      massive transfusion.

PMID- 9591975
TI  - Modification of the original Luque technique in the treatment of Duchenne's
      neuromuscular scoliosis.
AB  - Luque segmental instrumentation with Galveston technique for pelvic fixation is
      generally used in the correction of Duchenne's neuromuscular spinal deformities
      with pelvic obliquity. Particularly difficult is the control of the lumbopelvic
      junction. Instrumentation failures and only mediocre correction of pelvic
      obliquity are reported. To obtain better sacropelvic anchorage and to improve
      pelvic correction, this technique was modified with the introduction of sacral
      screws in each S-1 pedicle and a device for transverse traction between the
      caudal right-angle bends of the L-rods. From 1988 and 1993, 25 consecutive
      patients (mean age, 14 years) were operated on using this technique. Before
      surgery, mean spinal deformity measured 68 degrees (range, 46-90 degrees), and
      pelvic obliquity, 21 degrees (range, 7-45 degrees). At the last examination (mean
      follow-up, 36 months), mean spinal curvature was 18 degrees (range, 3-37
      degrees), and pelvic obliquity was always <15 degrees (range, 0-15 degrees) with
      mean correction of 75%. No instrumentation failure or loss of correction >3
      degrees could be observed in the entire series. In every patient, a good sitting
      balance could be restored after surgery.

PMID- 9591977
TI  - Analysis and treatment of poor outcomes following in situ arthrodesis in
      adolescent spondylolisthesis.
AB  - In situ lumbosacral arthrodesis in the treatment of adolescent spondylolisthesis
      was evaluated in 39 patients. The clinical outcome an average of 4.7 years later
      was considered excellent or good in 82% of the cases based on their pain and
      gait. The quality of the fusion mass correlated with outcome. Those patients with
      the most severe kyphosis (slip angle) had the greatest chance of a poor result.
      Four patients required reoperation for pseudarthrosis or symptomatic compression
      of the cauda equina. Three of these were successfully treated with repeat
      arthrodesis or decompression with sacroplasty or both.

PMID- 9591978
TI  - Increasing lordosis of the occipitocervical junction after arthrodesis in young
      children: the occipitocervical crankshaft phenomenon.
AB  - Five children were treated before age 6 years with occipitocervical fusion for
      occipitocervical instability. Long-term (average, 11.8 years; range, 8.4-14.5
      years) follow-up revealed increasing lordosis across the fused segment in four of
      the patients, a finding we here refer to as the occipitocervical crankshaft
      phenomenon. On average, occipitocervical lordosis increased 1.06 degrees per
      level fused per year until skeletal maturity. Although such a progression might
      be expected, to our knowledge this is the first report of its occurrence.
      Compensatory subaxial motion was able to overcome this increase in all of the
      patients. We recommend occipitocervical fusion in a neutral or slightly flexed
      position in the very young child to account for this predictable increase in
      lordosis.

PMID- 9591979
TI  - Intravertebral spinal neurenteric cysts: a unique radiographic sign--"the hole-in
      one vertebra".
AB  - A well-defined circular defect in the midst of a complex vertebral anomaly,
      visible on a plain radiograph, is diagnostic of an intravertebral extension of a
      neurenteric cyst. It may represent a connecting stalk between a mediastinal cyst
      and an intraspinal lesion. The "hole-in-one" vertebra is an indication for a
      magnetic resonance imaging (MRI) scan. When surgical excision of a mediastinal
      cyst is undertaken, the intravertebral tract should be curetted to avoid
      recurrence.

PMID- 9591980
TI  - Scoliosis and trunk asymmetry in upper limb transverse dysmelia.
AB  - The incidence of scoliosis and trunk asymmetry were studied in 60 patients with
      upper limb dysmelia of the transverse type. The evaluations were based on
      radiographic measurements of the spine and scoliometer readings of the angle of
      trunk rotation (ATR), which were correlated with the side and level of the limb
      deficiency and also with leg length-inequality (LLI). Nineteen patients (31%) had
      a scoliosis between 10 and 19 degrees, whereas the curves were between 5 and 10
      degrees in another 30 patients and the remainder had no measurable curve. The
      scoliosis seemed at least partly to be of postural origin as LLI significantly
      correlated with the direction of the curves, but there was no correlation between
      the Cobb angles and the magnitude of LLI. The scoliometer readings did not
      correlate with the scoliosis or LLI. Our findings indicate that most patients
      with upper limb transverse amputations do not develop a significant scoliosis. A
      scoliometer screen has a low positive predictive rate for scoliosis and the
      diagnosis of scoliosis requires a radiograph of the spine.

PMID- 9591981
TI  - Surgical release of tethered spinal cord: survivorship analysis and orthopedic
      outcome.
AB  - Between January 1988 and February 1995, 133 tethered spinal cord-release
      procedures in 88 consecutive patients were performed at our institution and were
      used to determine survivorship data for surgical release of tethered spinal cord.
      The diagnoses included spinal dysraphism (67), achondroplasia (nine), isolated
      tethered cord (nine), cerebral palsy (three), and others (seven). Survivorship
      data were calculated for the initial and first-revision tethered cord release.
      There was a 50% revision rate by 5 years after initial tethered-cord release and
      a 57% revision rate by 2 years after a second release. Thirty-six patients were
      excluded for having <2 years of clinical follow-up, leaving 97 spinal cord
      releases in 52 patients available for outcome analysis. At a mean follow-up of
      4.4 years (range, 2-11.3), 58% of patients required one or more orthopedic
      procedures after tethered-cord release. The average number of orthopedic
      procedures per year before release (0.28/year) was found to increase after
      initial release (0.39/year; p < 0.05). These data demonstrate the frequent need
      for operative revision after index tethered-cord release, especially in children
      with spinal dysraphism. In addition, the need for orthopedic procedures after
      tethered spinal-cord release frequently persists.

PMID- 9591982
TI  - Multiple tarsal coalitions in the same foot.
AB  - I reviewed 60 cases of tarsal coalition seen at Texas Scottish Rite Hospital for
      Children over the last 10 years. Twenty-nine patients had plain films only and
      were excluded from the study. One patient was diagnosed with synovitis at the
      time of surgery and was also excluded. Thirty patients with 53 coalitions had
      computed tomographic (CT) and, in many cases, surgical documentation of a tarsal
      coalition. Of these 30 patients, six had multiple coalitions in the same foot.
      This article briefly summarizes the six cases and reviews the literature of
      multiple tarsal coalitions, both before and after the use of CT. I suggest that
      multiple coalitions in the same foot are more common than once thought and
      recommend CT evaluation of both feet in transaxial and coronal planes in patients
      with suspected tarsal coalition.

PMID- 9591983
TI  - Mitchell osteotomy for adolescent hallux valgus.
AB  - Sixty-nine Mitchell osteotomies augmented with smooth-pin fixation and a
      trapezoidal step-off osteotomy to maintain ray length were performed on 46
      adolescent patients with a painful hallux valgus deformity. Average follow-up
      time was 6 years. By using radiographic, clinical, and subjective patient data,
      we found an overall excellent or good result in 91% of cases. Nine feet were
      found to be cosmetically unsatisfactory, 11 required special shoewear, 10 had
      mild residual pain with high heels or strenuous running, and three had pain
      severe enough to restrict activities. Range of motion was normal in 56 feet,
      slightly decreased in 11 feet, and significantly reduced in two feet. We conclude
      that, given a success rate of 91%, this slightly modified Mitchell osteotomy is a
      satisfactory procedure for adolescent hallux valgus deformity with chronic bunion
      discomfort.

PMID- 9591984
TI  - Plantar-advancement skin flap for central ray resections in the foot: description
      of a technique.
AB  - A surgical technique using an advancement plantar skin flap to maintain the
      resection gap closure when performing central ray resections is described and
      illustrated. The concept, applicable to central polydactyly or polysyndactyly of
      the foot, was developed with goals of providing a skin tether to maintain a
      normally narrow foot as well as to improve the appearance of the surgical scar.

PMID- 9591985
TI  - Gait analysis and muscle strength in children with surgically treated clubfeet.
AB  - Twenty-three children who had unilateral surgery for idiopathic clubfeet
      underwent gait analysis and isokinetic muscle-strength testing at an average of
      10 years after surgical release. Ankle sagittal-plane kinematics were disturbed
      in 20 clubfeet. Fifteen children had an internal foot-progression angle. Genu
      valgum and knee hyperextension were common. Plantarflexion power was decreased by
      23% on the side of surgery (p = 0.00005). Quadriceps weakness (defined as a
      decrease in strength >10% of the nonoperated-on limb's strength) was seen in nine
      of 22 operated-on limbs and hamstring weakness in eight of 22. Gastrocsoleus
      weakness exceeded 10% in 16 of 21 clubfeet. Average weakness of the gastrocsoleus
      was 27% (p < 0.05). Ten-year analysis of children treated with clubfoot releases
      revealed disturbances in ankle motion and strength. Loss of plantarflexion power
      and gastrocsoleus strength can be predicted by Achilles tendon lengthening. Knee
      kinematic abnormalities and weakness also were seen. These abnormalities produce
      functional difficulties in gait and may lead to degenerative changes later.

PMID- 9591986
TI  - Ilizarov applications in the pediatric foot.
AB  - We applied the Ilizarov technique and apparatus to the correction of 24 severe
      foot deformities in 21 children. We were able to achieve a serviceable
      plantigrade foot in all cases, with nine feet achieving an excellent result, 12
      achieving a good result, three being fair, and none poor. Ilizarov's technique
      and apparatus offer an excellent adjunct for treating carefully selected severe
      foot deformities in children.

PMID- 9591987
TI  - Management of clubfoot deformity in amyoplasia.
AB  - Forty-one clubfeet in 22 patients with amyoplasia were studied retrospectively at
      a mean duration after surgery of 118 months (range, 45-253). The clubfeet were
      managed by a regimen including initial stretching casts, posteromedial release,
      and postoperative splinting at night. The mean age at the time of surgery was 7.3
      months. Correction of deformity without recurrence was achieved in 11 (27%).
      Recurrent deformity was corrected by serial casting in eight feet and required
      secondary operative procedures in 20 feet. In the feet without recurrence of
      deformity, the duration of splinting at night after surgery was significantly
      longer than in those with recurrence (p < 0.05). At follow-up, 39 (95%) feet were
      plantigrade and were considered satisfactory. Our findings suggest that most
      clubfeet in amyoplasia can be effectively corrected by posteromedial release and
      that the recurrence of deformity can be reduced by splinting at night and often
      corrected by serial cast treatment.

PMID- 9591988
TI  - Pathologic fractures through nonossifying fibromas: is prophylactic treatment
      warranted?
AB  - Twenty-two patients with large nonossifying fibromas (NOFs) in weight-bearing
      bones were studied to evaluate risk of pathologic fracture. Previous reports
      suggest an absolute size threshold for NOFs beyond which there is a reasonable
      chance of impending fracture. In this series, 13 (59%) large NOFs had not had
      pathologic fracture despite exceeding the previously established size threshold.
      Four of the patients had fractures of the long bone in which the NOF was located
      without the fracture involving the lesion. In the nine (41%) patients in whom
      pathologic fracture occurred, healing was uneventful after closed reduction and
      cast immobilization. Whereas absolute size parameters may be useful in predicting
      pathologic fracture rate, they do not imply a requirement for prophylactic
      curettage and bone grafting. The majority of patients with large NOFs can be
      monitored without surgical intervention, and fractures can be successfully
      managed with nonoperative treatment.

PMID- 9591989
TI  - Treatment of simple bone cysts in children with curettage and cryosurgery.
AB  - A retrospective study in children with simple or unicameral bone cysts treated
      with curettage, cryosurgery, and bone grafting was conducted. The purpose of this
      study was to evaluate local tumor control and bony healing after this method of
      treatment. Five (12%) of 42 treated patients had a local recurrence with a mean
      clinical follow-up of 24.5 months. Surgical complications consisted of two
      superficial wound infections, one radial nerve palsy, and two fractures, which
      all resolved completely. A review of the literature was performed to compare our
      results with historic controls using steroid-injection therapy and curettage with
      bone grafting alone. We believe that the use of cryosurgery as adjuvant therapy
      in the surgical treatment of simple bone cysts is of value in controlling local
      recurrences and achieving bony consolidation.

PMID- 9591990
TI  - Cast and brace treatment of eosinophilic granuloma of the spine: long-term follow
      up.
AB  - Eosinophilic granuloma of the skeleton is rarely reported in the literature. The
      incidence of vertebral involvement varies between 7.8 and 25% and it is generally
      a solitary lesion, with a predilection for the male sex in the first decade of
      life. The prognosis is favorable also for the vertebral body's tendency for
      reconstruction. A recovery of the somatic structure is apparently much improved
      by eliminating or reducing mechanical stress by means of bed rest and the use of
      plaster casts or braces. We examined nine patients treated at the Orthopedics
      Clinic of Padova University, and with a follow-up of > or = 10 years. treated
      with plaster casts and spinal orthoses. The study was based on the modified
      Nesbit radiographic classification in 4 grades of severity depending on the
      height of the vertebral body involved. Long-term follow-up revealed no painful
      symptoms and a virtually total recovery of somatic structure in five cases,
      whereas four patients still showed a varying degree of somatic alteration. The
      osteogenic capacity of the intact ring epiphysis and ossifying metaplastic
      processes were assumed to be the mechanisms contributing, together with a reduced
      mechanical load, to reconstruction of the vertebral somatic structure.

PMID- 9591991
TI  - de Pablos J, Alfaro J, Barios C. Treatment of adolescent Blount disease by
      asymmetric physeal distraction. J Pediatr Orthop 1997;17:54-8.

PMID- 9591992
TI  - Hip subluxation in cerebral palsy: what should be done for the spastic child with
      hip subluxation?

PMID- 9591993
TI  - Psoas release at the pelvic brim in ambulatory patients with cerebral palsy:
      operative technique and functional outcome.
AB  - Seventeen patients with cerebral palsy (29 hips) underwent psoas recession at the
      pelvic brim. The operative technique was a direct anterior approach, lateral to
      the femoral sheath. There were no infections or nerve or arterial injuries. After
      surgery, clinical examination revealed that fixed hip-flexion contractures
      decreased significantly in all patients. All of the subjects retained the ability
      to flex the hip against gravity and against manual resistance. All of the
      subjects underwent pre- and postoperative gait analysis. Stance-phase dynamic
      minimum hip flexion decreased significantly. Dynamic pelvic tilt improved to a
      statistically significant level for the younger children but did not for the
      group as a whole. There was less improvement with increasing age. Step length was
      significantly increased and cadence significantly decreased in all patients. We
      conclude that psoas recession at the pelvic brim, by using the anterior approach,
      lateral to the femoral sheath, is a safe, reliable, and effective procedure for
      children with cerebral palsy who have excessive anterior pelvic tilt and
      excessive dynamic hip flexion or hip-flexion contracture.

PMID- 9591994
TI  - Soft-tissue release for spastic hip subluxation in cerebral palsy.
AB  - Children with spastic hip subluxation secondary to cerebral palsy were treated
      with a standard protocol that focused on early detection of the subluxation using
      physical examination and anteroposterior pelvis radiographs. Using limited hip
      abduction of < or =30 degrees and subluxation of > or =25% migration percentage
      as indications, patients had open adductor and iliopsoas lengthenings with
      immediate postoperative mobilization and no abduction bracing. The protocol was
      applied to 74 children with a mean age of 4.5 years and had 147 hips surgically
      addressed. Of these hips initially, 20% were normal (migration percentage <25%),
      52% were mildly subluxated (migration percentage 25-39%), 22% were moderately
      subluxated (migration percentage 40-59%), and 6% were severely subluxated
      (migration percentage > or =60%). At a final postoperative follow-up of 39
      months, 54% of these hips were classified as good (migration percentage <25%),
      34% were fair (migration percentage 25-39%), and 12% were poor (migration
      percentage > or =40%). Of this patient population, 69% were nonambulators and
      their outcomes were not statistically different from children who could walk. No
      child developed an abduction contracture or wide-based gait that required
      treatment. With early detection and applying this treatment algorithm, 80% of
      children with spastic hip disease should have good or fair outcomes. Longer
      follow-up will be required to determine how many children will need bony
      reconstruction to maintain stable and located hips at the conclusion of growth.

PMID- 9591995
TI  - Long-term effects of intertrochanteric varus-derotation osteotomy on femur and
      acetabulum in spastic cerebral palsy: an 11- to 18-year follow-up study.
AB  - An intertrochanteric femoral osteotomy is carried out to correct intoeing gait
      and to improve hip centration in patients with spastic cerebral palsy. The long
      term effect of such osteotomies on the neck-shaft angle (NSA) and anteversion
      angle (ATA), as well as on hip-joint centration, was evaluated in 63 hips of 45
      patients with observation times of 11-18 years (mean, 15.4). The postoperative
      loss of correction of the NSA and ATA was the more pronounced the younger the
      patients were at the time of intervention. This was particularly true when the
      hip joint was subluxated or dislocated and when the operation was done before the
      age of 4 years. Patients of this age group lost 96% of the correction of the NSA
      and 42% of the ATA. Hip centration always improved, but corrective femoral
      osteotomy alone did not result in a sufficient coverage in cases of subluxation
      and dislocation in the short and long term.

PMID- 9591996
TI  - Reconstruction of the dysplastic spastic hip with peri-ilial pelvic and femoral
      osteotomy followed by immediate mobilization.
AB  - All children with cerebral palsy who had a pelvic osteotomy performed by the
      senior author (F.M.) from 1989 through 1991 were reviewed. Indications for
      operative reconstruction were failed muscle lengthening in a child younger than 8
      years or a painful hip. The operative procedure included adductor muscle
      lengthening, varus shortening femoral osteotomy, and peri-ilial pelvic osteotomy.
      Patients were immediately mobilized after surgery by physical therapy. Fifty-one
      children had reconstruction of 49 subluxated and 21 dislocated hips. Femoral and
      pelvic osteotomies were performed on 59 hips, and 11 hips had only a femoral
      osteotomy. Forty-nine hips had adductor muscle lengthening, and 27 hips had
      femoral osteotomy to provide for relief of contractures. At mean follow-up of 34
      months, two hips in two patients had redislocated, requiring repeated surgery.
      Two hips remained subluxated and asymptomatic. Twenty-three hips in 18 patients
      were painful before surgery. One hip continued with severe pain after surgery,
      requiring further surgery. Three hips continued with mild pain not requiring
      surgery, and 14 (82%) hips had complete pain relief. Of 37 caretakers
      interviewed, 80% felt the procedure was beneficial and would recommend it to
      others. Eight percent were uncertain, and 6% (two caretakers) thought it was not
      helpful.

PMID- 9591997
TI  - The effect of rectus EMG patterns on the outcome of rectus femoris transfers.
AB  - Rectus femoris transfer to the sartorius is performed in children with cerebral
      palsy to treat stiff-knee gait. To determine whether preoperative
      electromyographic (EMG) activity of the rectus femoris is predictive of outcome,
      we studied 25 children with stiff-knee gait who had preoperative EMG gait
      analysis before rectus femoris transfer. Fifteen patients had bilateral surgery,
      and 10 patients had unilateral surgery. The mean age at surgery was 9.6 years for
      the retrospective review. Patients were divided into three groups based on the
      recorded EMG patterns of the rectus femoris during the gait cycle. Group I
      patients had predominant swing-phase activity only. Group II patients had
      constant rectus activity through the entire gait cycle. Group III patients had
      normal rectus, defined as minimal EMG activity in the last 75% of swing phase. A
      repeated gait analysis at a mean of 1.5 years after surgery was available for
      comparison. In group I, mean peak knee flexion increased 26 degrees after surgery
      from 44 to 70 degrees. In group II, mean peak knee flexion increased 18 degrees
      after surgery from 51 to 69 degrees. In group III, mean peak knee flexion
      increased 12 degrees from 54 to 66 degrees. Results of this study show the
      greatest improvement in outcome, as measured by knee flexion, occurred in group I
      in which the rectus fired predominantly in swing phase. Preoperative EMG patterns
      are therefore useful in determining the outcome after rectus femoris transfer to
      the sartorius.

PMID- 9591998
TI  - Alterations in surgical decision making in patients with cerebral palsy based on
      three-dimensional gait analysis.
AB  - The purpose of this study was to compare surgical recommendations made by
      clinicians experienced in gait analysis when using information provided from the
      clinical examination and videotape, with recommendations made after the addition
      of kinematic, kinetic, and electromyographic (EMG) data. Ninety-one patients with
      a diagnosis of cerebral palsy were seen in the gait laboratory as part of the
      surgical decision-making process. Experienced clinicians reviewed video and
      clinical examination data for each patient and made surgical recommendations.
      Joint kinematics and kinetics and EMG data were then reviewed, and a second set
      of surgical recommendations was made. Comparisons between these recommendations
      showed that the addition of gait-analysis data resulted in changes in surgical
      recommendations in 52% of the patients, with an associated reduction in cost of
      surgery, not to mention the human impact of an inappropriate surgical decision,
      which is more likely without gait analysis. When changes in recommendations were
      made, an increase in surgical recommendations was observed for the gastrocnemius
      (59%) and rectus femoris (65%), whereas decreases were observed for the
      hamstrings (61%), psoas (78%), hip adductors (83%), femur (86%), and tibia (64%).

PMID- 9591999
TI  - Chronic physeal fractures in myelodysplasia: magnetic resonance analysis,
      histologic description, treatment, and outcome.
AB  - Thirteen myelodysplastic children with 19 chronic physeal fractures were treated.
      All were treated with prolonged immobilization (average, 5.8 months; range, 3-18
      months) in either braces or casts; four of the fractures required operative
      fixation to facilitate healing. All were healed at 4.8-years follow-up but, in
      four of the fractures, the growth plate closed prematurely. Three of the children
      underwent magnetic resonance imaging (MRI) of the injured physes, and one
      underwent physeal biopsy as part of her operative epiphysiodesis. Histologic
      analysis revealed three distinct zones of physeal pathoanatomy: a normal zone of
      proliferation; a thickened, disorganized zone of hypertrophy; and a vascularized
      zone of fibrous tissue adjacent to the metaphysis. On MRI, there was thickening
      of the physis and irregularity of the zone of provisional calcification. The
      physeal cartilage and the juxtametaphyseal fibrovascular tissue enhanced with
      gadolinium. These findings corroborate earlier mechanistic proposals for physeal
      injury in myelodysplasia: chronic stress or trauma to the poorly sensate limb
      produces micromotion at the zone of hypertrophy, yielding a widened, disorganized
      physis, and leading to fracture, displacement, and delayed union.

PMID- 9592000
TI  - Intraoperative latex anaphylaxis in children: classification and prophylaxis of
      patients at risk.
AB  - Over a 3-year period, in 36,075 general anesthetic anesthesia procedures done at
      our institution, 21 patients had type I (anaphylactic) intraoperative reactions
      to latex (phase 1). We subsequently established a system for classification of at
      risk patients with a corresponding regimen for prophylaxis used prospectively
      between January 1992 and July 1994 (phase II). Three groups of patients at risk
      for type I hypersensitivity reaction were identified, and a regimen for
      prophylaxis developed (based in part on protocols used in preparing patients who
      are allergic to radiocontrast media). Since using this protocol, the incidence of
      intraoperative anaphylaxis has decreased. During phase 2, 34,513 patients
      received a general anesthetic in the operating room, and there have been three
      cases of suspected intraoperative latex anaphylaxis; two of these three patients
      did not meet any of the risk criteria and therefore did not receive preoperative
      prophylaxis or avoidance of latex. Of these 34,513 patients, 86 at-risk patients
      received prophylaxis. A prospective study is needed to determine whether the
      pharmacologic prophylaxis is needed in addition to a latex-free environment.

PMID- 9592001
TI  - Postreduction computed tomography in developmental dislocation of the hip: part
      I: analysis of measurement reliability.
AB  - Twenty computed tomographic (CT) scans of infants in spica casts after closed or
      open reduction for developmental hip dislocation (DDH) were analyzed for intra-
      and interrater reliability. Ten measurements of infant hip anatomy were assessed
      by three raters by using standard statistical analysis. All six measurements of
      acetabular anteversion and lateral or posterior displacement of the femoral
      metaphysis from the acetabulum or from a modified Shenton's line drawn from the
      pubic rami demonstrated both intra- and interrater reliability. All four
      measurements of acetabular structure could not be reliably measured either within
      or between observers. We also introduced a new measurement based on the principle
      of Shenton's line to aid in the assessment of femoral-head location after
      reduction in patients with DDH; this was reliably determined both within and
      among observers.

PMID- 9592002
TI  - Postreduction computed tomography in developmental dislocation of the hip: part
      II: predictive value for outcome.
AB  - Computed tomographic (CT) scans were performed after closed reduction of 68
      dislocated hips in 53 infants in spica casts with developmental hip dislocation
      (DDH). Ten measurements were made on the CT scans including acetabular indices
      and anteversion, hip-abduction angle, lateral and posterior displacement of the
      femur from the acetabulum, and femoral displacement from a modified Shenton's
      line drawn from the pubic rami. By using analysis of variance, the correlation of
      each variable with outcome after reduction was determined, including the
      development of avascular necrosis or the need for further surgery because of
      residual dysplasia. None of the variables was predictive of the outcome of
      persistent hip dysplasia. The subsequent development of avascular necrosis was
      statistically associated with hip-abduction angles >55 degrees as measured on
      postreduction CT scans, with 20% of the involved hips developing avascular
      necrosis on subsequent follow-up.

PMID- 9592003
TI  - The morphology of residual acetabular deficiency in childhood hip dysplasia:
      three-dimensional computed tomographic analysis.
AB  - Seventy hips (in 48 patients) in children with residual dysplasia resulting from
      developmental dysplasia of the hip (DDH) were evaluated by using three
      dimensional computed tomographic (3DCT) imaging to clarify the nature and degree
      of acetabular and femoral head deformity. We noted four types of dysplastic
      acetabulae: type I, subtle deficiency of the acetabulum with a mild break in
      Shenton's line (24%); type II, anterosuperior deficiency (29%); type III,
      midsuperior deficiency (38%); and type IV, global deficiency (9%). In untreated
      DDH with complete dislocation, the deficiency was predictably midsuperior (type
      III). Isolated posterosuperior deficiency, which is common in neuromuscular
      conditions, was not seen in these normal children with DDH. The 3DCT method used
      produced a topographic "contact map" that replicates the contact relation between
      the acetabulum and the femoral head. Analyzing the femoral head-acetabular
      contact relation and the type of acetabular deficiency allows the surgeon to plan
      better surgical correction of hip dysplasia in children.

PMID- 9592004
TI  - Acute slipped capital femoral epiphysis: the value and safety of urgent
      manipulative reduction.
AB  - A 40-year experience consisting of 91 cases of acute slipped capital femoral
      epiphysis (SCFE) was reviewed to assess the safety of manipulative reduction and
      to determine whether urgent reduction has an effect on the development of
      avascular necrosis (AVN) of the capital femoral epiphysis. All patients had a
      history of sudden onset of severe hip pain and were documented to have an
      unstable (acute) slipped epiphysis. Treatment modalities included manipulative
      reduction under general anesthesia followed by internal fixation (41 hips),
      epiphysiodesis and internal fixation (15 hips), epiphysiodesis and cast
      immobilization (31 hips), and cast immobilization alone (three hips). One case
      was treated with cast immobilization after reduction by skeletal traction.
      Patient follow-up averaged 44 months, and ranged from 12 to 216 months.
      Radiographic review identified 13 (14%) cases of AVN in the series of 91 hips. Of
      42 hips reduced in <24 h from presentation, AVN developed in three (7%). Of 49
      hips reduced in >24 h from presentation, AVN developed in 10 (20%). Manipulative
      reduction of the acute SCFE may be accomplished without increased risk of AVN.
      Time to reduction may be an important risk factor for development of AVN after
      acute SCFE.

PMID- 9592005
TI  - The HLA phenotype in slipped capital femoral epiphysis.
AB  - The HLA genotypes of six patients with acute grade I slipped capital femoral
      epiphysis as determined by microlymphocytotoxic technique revealed HLA-DR4 as
      their phenotypes. These results contradict the previously reported HLA-B12 as the
      phenotype of patients with slipped capital femoral epiphysis.

PMID- 9592006
TI  - Tibial torsion in chronic, stable slipped capital femoral epiphyses: evaluation
      by CT scan.
AB  - Externally rotated gait is a hallmark of slipped capital femoral epiphysis (SCFE)
      attributed to the change of proximal femur structure. This study investigated the
      potential role of abnormal tibial torsion in 44 patients with chronic, stable
      SCFE. Comparison of the tibiae of the involved side with the uninvolved side and
      with previously published normal values showed no evidence of tibial torsional
      abnormalities in these patients.

PMID- 9592007
TI  - Metaphyseal histology and magnetic resonance imaging in Legg-Calve-Perthes
      disease.
AB  - Cylindrical biopsy specimens from the proximal femoral metaphysis were obtained
      in conjunction with surgery in 22 patients with Legg-Calve-Perthes disease. The
      histopathological examination revealed fat necrosis, vascular proliferation, and
      focal fibrosis indicating previous episodes of ischemia. There was no correlation
      between the histopathological findings and the corresponding magnetic resonance
      images.

PMID- 9592008
TI  - Monitoring peripheral nerve function during external fixation of upper
      extremities.
AB  - Limb lengthening of the upper extremity using external fixation devices is
      associated with a high risk of neurovascular impairment. To aid early detection
      of nerve injury, intraoperative monitoring of neural function was performed in
      five patients undergoing Ilizarov-type circular external-fixator application. The
      apparatus was applied to the humerus in two cases and to the forearm in the other
      three cases. The function of ulnar, median, and radial nerves was assessed
      continuously throughout the surgery by using sensory-evoked potential (SEP)
      monitoring technique. The responses were elicited by stimulation of these nerves
      in the distal forearm with recording at Erb's point and over the anterior
      cervical spine. During apparatus application, radial-response attenuation was
      identified in two instances. No corrective actions were performed in one case,
      and the patient had symptoms of radial nerve deficit postoperatively. In the
      other case, prompt removal of the offending half-pin after the detection of
      electrophysiologic abnormalities resulted in subsequent response restoration and
      the avoidance of postoperative nerve dysfunction. Sensory-evoked potential
      monitoring proved to be a reliable indicator of nerve compromise during external
      fixation of upper extremities and may be considered a valuable surgical adjunct.

PMID- 9592009
TI  - Ilizarov treatment of congenital pseudarthroses of the tibia.
AB  - Eleven children with congenital pseudarthrosis of the tibia were treated with the
      Ilizarov device. This was successful in nine of 11 patients with an average of
      322 days in the fixator and 1.6 additional surgeries. Two patients eventually had
      amputations. These results demonstrate this to be an effective tool for this
      complex condition, but amputation should be considered if union is not achievable
      with this method and other procedures have previously been attempted.

PMID- 9592010
TI  - Congenital pseudarthrosis of the tibia associated with neurofibromatosis-1:
      treatment with Ilizarov's device.
AB  - We reexamined 21 patients with congenital pseudarthrosis of the leg (congenital
      pseudoarthrosis of the tibia; CPT) associated with neurofibromatosis-1 (NF-1), >
      or =2 years after the termination of treatment, for a statistical study of the
      results obtained by using Ilizarov's external fixator. Of the 21 tibias operated
      on, 17 consolidated after the first treatment, whereas four did not. Of the 17
      consolidated tibias, four refractured and were retreated by using a variety of
      methods. Only one healed. At follow-up, which occurred > or =2 years after the
      removal of the fixator, the results were nine consolidations without deformities
      or with shortening <2 cm, five consolidations with axial deviation, and seven
      nonconsolidations. The statistically significant results were that (a) patients
      who were aged 5 years or older at operation had better results, and (b) the
      assembly II (resection of CPT stumps and their short-term compression possibly
      associated with corticotomy or epiphyseal distraction to correct limb
      discrepancy) gave better final results compared with the other device assemblies.
      We conclude that treatment with Ilizarov's fixator allows (a) a good percentage
      of healing over time (66.7%), especially in cases of normotrophic and cystic CPT;
      (b) further operations with or without the fixator to correct secondary or
      residual axial deviation; and (c) correction of limb discrepancy. This treatment
      avoids risking injury to the healthy contralateral leg. Additionally, for
      treatments that do not achieve satisfactory results, other treatment methods are
      not excluded. The CPT still remains a difficult problem for the orthopedic
      surgeon to solve.

PMID- 9592011
TI  - Ilizarov technique in the treatment of congenital pseudarthrosis of the tibia.
AB  - This study analyzes the risks and benefits of Ilizarov's technique in congenital
      pseudarthrosis of the tibia (CPT). This was a retrospective review of 14 patients
      treated between 1985 and 1993 for CPT, by using Ilizarov's technique. In 12
      cases, this technique was used after failure of previous surgical treatment.
      Realignment, end-to-end compression, and leg lengthening were undertaken in all
      the cases, without excision of the pseudarthrosis site. The mean fixation
      duration was 7.8 months. Union was achieved with the initial treatment in seven
      cases. Bone grafting was used in six of the seven remaining cases and achieved
      bone healing in three of them. Refracture occurred in one case, and ended with
      nonunion. At 3.5-year average follow-up, the tibia was united in nine cases. We
      found that the best indications for Ilizarov's technique in CPT were the
      normotrophic and hypertrophic types of pseudarthrosis (Apoil II), after the age
      of 5 years. Secondary massive bone grafting is to be considered in some cases.
      The major disadvantage of this method is the lack of excision of the
      pseudarthrosis site. Even after healing is achieved, the bone remains dystrophic
      and fragile and necessitates a permanent protective orthosis, until the end of
      bone growth.

PMID- 9592012
TI  - Management of late-onset tibia vara in the obese patient by using circular
      external fixation.
AB  - Previously published series of surgery for late-onset tibia vara reported a
      significant number of complications and fair or poor results. Obesity in many of
      these patients makes surgical intervention an even more daunting prospect.
      Circular external fixation is applicable to almost any limb size and allows
      weight bearing as tolerated, with gradual adjustment of alignment. Twenty-five
      tibiae in 17 patients who exceeded their ideal body weight by > or =50% underwent
      correction of late-onset tibia vara with the Ilizarov technique. Average age at
      surgery was 11 years 7 months (range, 7 years 8 months to 15 years 11 months).
      Mean varus deformity was 27 degrees (range, 10-55 degrees). Treatment time
      averaged 12 weeks in patients without lengthening and 16.9 weeks in those
      requiring lengthening (mean, 3.5 cm). All patients achieved alignment within 5
      degrees of normal. Complications included one delayed union, premature
      consolidation in one, and two residual limb-length inequalities. There were no
      cases of osteomyelitis, compartment syndrome, or nerve palsy. These results are a
      significant improvement over reports of traditional methods in these difficult
      patients.

PMID- 9592013
TI  - Thoracic outlet syndrome in children.

PMID- 9592014
TI  - The making of an erythroid cell. Molecular control of hematopoiesis.
AB  - The number of circulating red cells is regulated by the daily balance between two
      processes: the destruction of the old red cells in the liver and the generation
      of new cells in the bone marrow. The process during which hematopoietic stem
      cells generate new red cells is called erythropoiesis. This manuscript will
      describe the molecular mechanisms involved in the process of erythroid
      differentiation as we understand them today. In particular it will review how
      erythroid specific growth factor-receptor interactions activate specific
      transcription factors to turn on the expression of the genes responsible for the
      establishment of the erythroid phenotype.

PMID- 9592016
TI  - The role of homeobox genes in hematopoiesis.
AB  - Homeobox genes encode transcription factors containing a common DNA-binding motif
      found in virtually all animal species. Different homeobox gene families have
      evolved which encode homeodomains of different types or classes and thus far
      approximately 170 homeobox genes have been cloned. Homeoproteins are involved in
      the control of animal development and several lines of evidence strongly suggest
      that they may contribute to the regulation of hematopoiesis. Many members of this
      large family are expressed in blood cells. Moreover, homeobox containing genes
      have been involved in translocation events occurring in certain leukemias and
      lymphomas. Furthermore a number of studies indicate that modulation of homeobox
      gene expression may induce alterations in proliferative, differentiative or
      phenotypic characteristics of hematopoietic cells. Although the function of each
      individual gene has not been clearly defined there is strong evidence for
      cooperativity among homeoproteins indicating that regulatory combinations of
      homeobox genes may play a pivotal role in controlling survival, proliferation and
      differentiation of hematopoietic cells.

PMID- 9592015
TI  - Mpl ligand or thrombopoietin: biological activities.
AB  - Thrombopoietin (TPO) or Mpl ligand is the primary physiological regulator of
      platelet production. This cytokine is the most potent stimulator of the
      proliferation and differentiation of MK progenitor and precursor cells in vitro.
      It also acts additively or synergistically with several cytokines on progenitor
      cells from various hematopoietic lineages, including the primitive stem cells.
      The factor is an extremely potent thrombocytopoietic agent when administrated to
      normal animals, and it accelerates platelet and erythropoietic recovery in
      several models of myelosuppression. Phase I/II clinical trials are ongoing with
      no detectable adverse effects. Mpl ligand does not induce platelet aggregation,
      but it lowers the platelet sensitivity to physiological dose of agonists. In
      experimental mouse models, high and chronic dose of Mpl ligand results in
      myelofibrosis. TPO is constantly produced by the liver and the kidney; its
      plasmatic clearance occurs by binding to its receptor expressed on megakaryocytes
      and platelets. However, the full spectrum of the biological effects of this new
      cytokine is not fully understood, in particular its the role in the terminal
      stage of platelet production. In the near future, it is likely that new insights
      will be obtained in the physiopathological mechanisms underlying abnormal
      platelet production in human.

PMID- 9592017
TI  - Cytokine effect on ex vivo expansion of haemopoietic stem cells from different
      human sources.
AB  - Human pluripotential stem cells (PSC) are currently the target for
      transplantation attempts and genetic manipulation. We have therefore investigated
      the frequency and the expansion potential of PSC's in different types of blood
      samples. CD 34+ cells were thus obtained from human bone marrow (BM), as well as
      from peripheral blood (PB) and cord blood (CB) samples. After immuno-magnetic
      separation the highest yields of CD 34+ cells were from BM (1.08-2.25%) and CB
      (0.42-1.32%) while PB samples gave much lower values. Suspension cultures of
      PSC's from the three sources were then set up, in the presence of combinations of
      haemopoietic growth factors. A remarkable amplification of the nucleated cell
      pool was observed reaching a maximum between 10 and 15 days of culture; earliest
      and maximum expansion (up to 220-fold) was achieved when Erythropoietin (Epo) was
      added to the culture medium, but this resulted in reduction of colony-forming
      cells and differentiation into erythroid progenitors. Clonogenic tests for BFU
      E's derived colonies showed a peak value at 5 days of liquid culture. Further
      studies are advisable to establish the best cytokine combination for a valuable
      ex vivo expansion, coupled with preservation of stem cell properties.

PMID- 9592018
TI  - Hematopoietic growth factors in autologous transplantation.
AB  - Hematopoietic growth factors (HGFs) sustain the survival, proliferation and
      differentiation of hematopoietic stem cells and some functions of mature blood
      cells. In man several HGFs have been characterised and cloned so far, and this
      has allowed investigators to confer the rationale for the clinical application of
      these molecules in hematology and oncology. In particular G-CSF and GM-CSF are
      currently utilised to abrogate the hematological toxicity of chemotherapy for
      standard and dose-intensified therapy, neutropenia following bone marrow and
      peripheral blood stem cell transplantation. Moreover there has recently been
      great interest in the ex vivo expansion of hematopoietic stem and progenitor
      cells for a variety of applications, such as in vitro tumor cell purging or for
      reducing the volume of blood processed by the leukapheresis. Several combinations
      of HGFs have been described to sustain the ex vivo survival and proliferation of
      these cells disclosing new opportunities in the field of stem cells transplants.

PMID- 9592019
TI  - Hodgkin's disease: a disorder of dysregulated cellular cross-talk.
AB  - Hodgkin's disease (HD) is a peculiar type of human malignant lymphoma
      characterized by a very low frequency of tumor cells, the so called Hodgkin and
      Reed-Sternberg (H-RS) cells, embedded in a hyperplastic background of non
      neoplastic (reactive) cells recruited and activated by H-RS cells-derived
      cytokines. H-RS cells can be functionally regarded as antigen-presenting cells
      (APC) able to elicit an intense, but anergic and ineffective, T-cell mediated
      immune response along with a hyperplastic inflammatory reaction which involves
      several cell types including T- and B-cells, neutrophils, eosinophils, plasma
      cells, fibroblasts and stromal cells. In tissues involved by HD, malignant H-RS
      cells and their reactive neighboring cells are able to cross-talk via a complex
      network of cytokine- and cell contact-dependent interactions. As a result of such
      interactions, mediated by specific surface receptors and adhesion molecules on
      both tumor and non-neoplastic cells, H-RS cells may receive several proliferative
      and anti-apoptotic signals favoring the cellular expansion and tumor cell
      survival in HD. The ineffective T-cell immune response elicited by the abnormal
      APC function of H-RS cells may further contribute to the biologic and clinical
      progression of HD. Innovative therapeutic strategies aimed at blocking the
      pathways of dysregulated cellular cross-talk among H-RS cells and bystander
      reactive cell populations might be beneficial in the treatment of HD patients.

PMID- 9592020
TI  - Natural and therapeutically-induced antibodies to cytokines.
AB  - Serum samples obtained from non-immunocompromised patients treated
      therapeutically with recombinant cytokines (e.g. Il-1alpha; Il-1beta; Il-2 to Il
      18; IFNalpha; GM-CSF; G-CSF; etc.) often reveal the presence of high affinity
      anti-cytokine antibodies. Antibody Fab binding in a saturable manner by ELISA and
      RIA or western immunoblotting prove their specificity. Antibody level often
      increases in these patients with repeated cytokine administration, suggesting
      boosts of antigen stimulation. However, the appearance in circulation of auto
      antibodies to exogenous cytokine is not always associated with a decreased
      clinical response to therapy. The demonstration that non-neutralizing auto
      antibodies to several natural cytokines can be found even in sera of normal
      healthy individuals never treated before with cytokines and particularly during
      the last trimester of pregnancy and in cord-blood, suggests that these naturally-
      occurring and therapeutically-induced auto-antibodies may exert different
      functions, not only as inhibitors or antagonists but also as beneficial
      physiological cytokine carriers or regulators of their activity.

PMID- 9592022
TI  - Effects of tachykinin receptor antagonists on the rat jejunal distension pain
      response.
AB  - Distension of the rat intestine causes a cardiovascular response which is
      indicative of nociception. Since tachykinins are involved in nociception, we
      tested the effect of neurokinin receptor antagonists against the distension
      induced response. The jejunal distension-induced depressor responses were
      inhibited in a dose-dependent fashion by CP 99,994 (+)-(2S,3S)-3-(2
      methoxybenzylamino)-2-phenylpiperidine, tachykinin NK1 receptor antagonist, ED50
      = 0.8 mg/kg) and SR 48968 (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2
      (3,4-dichloropheny l)butyl]benzamide, tachykinin NK2 receptor antagonist, ED50 =
      0.7 mg/kg). SR 142801 (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3
      yl)prop yl)-4-phenylpiperidin-4-yl)-N-methylacetamide, tachykinin NK3 receptor
      antagonist, 0.3-10 mg/kg) did not significantly affect the depressor responses to
      jejunal distension. In addition, CP 99,994 (3 mg/kg) and SR 48968 (3 and 10
      mg/kg) reduced sensitivity to distension as revealed by a 2.7-fold (CP 99.994, 3
      mg/kg), 2.6-fold (SR 48968, 3 mg/kg) and 4.7-fold (SR 48968, 10 mg/kg) increase
      in the threshold pressure. Intestinal compliance was not affected by the
      antagonists. In conclusion, these results suggest that tachykinin NK1 and NK2 but
      not NK3 receptors are possibly involved in the rat jejunal distension pain
      response.

PMID- 9592021
TI  - Spinal and supraspinal antinociceptive action of dipyrone in formalin, capsaicin
      and glutamate tests. Study of the mechanism of action.
AB  - Dipyrone injected intraperitoneally (i.p.) or subplantarly into the mouse paw
      caused dose-related antinociception against the early and the late phases of
      formalin-induced licking, with mean ID50 values of 154.5 and 263.7 micromol/kg,
      and 2.6 and 1.2 micromol/paw, respectively. Given either by
      intracerebroventricular (i.c.v.) or by intrathecal (i.t.) routes, dipyrone
      produced a similar inhibition of both phases of the formalin-induced licking,
      with mean ID50 values of 0.4 and 1.3 micromol/site, and 0.4 and 0.9 micromol/site
      against the early and the late phase of the formalin response, respectively.
      Dipyrone, given by i.p., subplantar, i.t. or i.c.v. routes, caused dose-related
      antinociception of capsaicin-induced licking. The mean ID50 values were: 207.6
      micromol/kg, 2.2 micromol/paw, 0.4 micromol/site and 0.14 micromol/site,
      respectively. In addition, dipyrone given i.p. caused a significant increase of
      the latency both in the hot-plate and the tail-flick assays. Dipyrone, given
      i.p., i.t. or i.c.v., reversed significantly the hyperalgesia caused by i.t.
      injection of glutamate, with mean ID50 values of 9 micromol/kg, 29 nmol/site and
      94 nmol/site, respectively. The antinociception caused by dipyrone was not
      influenced by naloxone, L-arginine, phaclofen, glibenclamide, p
      chlorophenylalanine methyl ester, pertussis toxin or by adrenal gland hormones,
      when assessed against the formalin assay. Dipyrone analgesic action was not
      secondary to its anti-inflammatory effect, nor was it associated with non
      specific effects such as muscle relaxation or sedation actions of animals.
      Dipyrone at a higher concentration caused significant inhibition of [3H]glutamate
      binding (37%) in cerebral cortical membranes from both mice and rats. However,
      dipyrone had no significant effect on brain constitutive neuronal nitric oxide
      synthase activity. It is concluded that dipyrone produces peripheral, spinal and
      supraspinal antinociception when assessed on formalin and capsaicin-induced pain
      as well as in glutamate-induced hyperalgesia in mice. Dipyrone antinociception
      seems unlikely to involve an interaction with the L-arginine-nitric oxide
      pathway, serotonin system, activation of Gi protein sensitive to pertussis toxin.
      interaction of ATP-sensitive K+ channels, GABA(B) receptors, or the release of
      endogenous glucocorticoids. However, a modulatory effect on glutamate-induced
      hyperalgesia and, to a lesser extent, an interaction with glutamate binding
      sites, seems to account for its analgesic action.

PMID- 9592023
TI  - Involvement of the midbrain periaqueductal gray 5-HT1A receptors in social
      conflict induced analgesia in mice.
AB  - Recent results from our laboratory have shown that 30-bites social conflict in
      mice produces a high-intensity, short-term analgesia which is attenuated by
      systemically injected 5-HT1A receptor agonists, such as BAY R 1531 (6-methoxy-4
      (di-n-propylamino)-1,3,4,5-tetrahydrobenz((c,d)indole hydrochloride) and
      gepirone. The present study investigated the effects of these drugs, as well as
      the 5-HT1A receptor antagonist WAY 100135 (N-tert-butyl-3-(4-(2
      methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide ) injected into the midbrain
      periaqueductal gray matter of mice on 30-bites analgesia. Four to five days after
      guide-cannula implantation, each mouse received microinjection of gepirone (30
      nmol/0.2 microl), BAY R 1531 (10 nmol/0.2 microl), WAY 100135 (10 nmol/0.2
      microl), saline (0.9% NaCl) or vehicle (saline + 4% Tween 80) 5 min before either
      an aggressive (30 bites) or a non-aggressive interaction. Nociception was
      assessed by the tail-flick test made before as well as 1, 5, 10 and 20 min after
      social interaction. The full 5-HT1A receptor agonist BAY R 1531 blocked, whereas,
      WAY 100135 and gepirone intensified 30-bites analgesia. Neither non-aggressive
      interaction, per se, nor the three compounds given after this type of social
      interaction significantly changed nociception. These results indicate that 5-HT1A
      receptors in the periaqueductal gray inhibit analgesia induced by social conflict
      in mice.

PMID- 9592024
TI  - Chlormethiazole anticonvulsive efficacy diminished by N-methyl-D-aspartate but
      not kainate in mice.
AB  - The aim of this study was to evaluate the effect of N-methyl-D-aspartate (NMDA)
      and kainate used at nonconvulsive doses upon protective efficacy of
      chlormethiazole against maximal electroshock-induced seizures. NMDA (50 mg/kg,
      i.p.) reduced the anticonvulsant potency of chlormethiazole increasing its ED50
      value from 126.9 to 155.0 mg/kg. The effect of NMDA was completely reversed by
      the competitive NMDA receptor antagonist D-(E)-2-amino-4-methyl-5-phosphono-3
      pentenoic acid (CGP 40116) (0.06 mg/kg i.p.). Kainic acid (9 mg/kg i.p.) did not
      affect the anticonvulsive properties of chlormethiazole. Our results suggest that
      NMDA but not kainate receptor-mediated events participate in the anticonvulsant
      action of chlormethiazole.

PMID- 9592025
TI  - Effect of alpha2-adrenoceptor stimulation on isolated canine Purkinje fiber
      contraction.
AB  - We have recently identified the presence of postjunctional alpha2-adrenoceptors
      in canine Purkinje fibers. In this study, we examined the effects of alpha2
      adrenoceptor stimulation on the contraction strength of isolated Purkinje fibers.
      Exposure to the alpha2-adrenoceptor specific agonist and antagonist, UK 14,304 (5
      bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) and yohimbine (17
      hydroxyyohimban-16-carboxylic acid methyl ester hydrochloride) alone at 0.1
      microM respectively, did not produce any significant effect on Purkinje
      contraction strength. Purkinje contraction strength was augmented by
      isoproterenol (0.1 microM), forskolin (0.1 microM), or 8-bromo-adenosine cyclic
      2',3'-monophosphate (8-bromo-cAMP, 10 microM). UK 14,304 significantly reversed
      the effects of isoproterenol and forskolin but not those of 8-bromo-cAMP on
      Purkinje contraction strength. After incubation with pertussis toxin, the
      positive inotropic effect of forskolin on Purkinje contraction strength remained
      intact, but the forskolin effect could no longer be reversed by UK 14,304. These
      results suggest that the postjunctional alpha2-adrenoceptors in canine Purkinje
      fibers are coupled to a pertussis toxin-sensitive G protein, probably Gi.
      Stimulation of the alpha2-adrenoceptor antagonizes the effect of beta
      adrenoceptor stimulation on Purkinje contraction strength in an accentuated
      antagonism manner.

PMID- 9592027
TI  - Reciprocal interactions among neuropeptides and adenosine in the cardiovascular
      system of rats: a role of K(ATP) channels.
AB  - Possible reciprocal interactions among vasoactive intestinal polypeptide (VIP),
      calcitonin gene-related peptide (CGRP) and adenosine were investigated in
      anesthetized rats. Changes in arterial blood pressure were taken as a parameter
      to evaluate the interactions. The i.v. bolus injections of VIP (0.3 or 1 microg
      kg(-1)), CGRP (0.1 or 0.3 microg kg(-1)) and adenosine (1-100 microg kg(-1)),
      like acetylcholine (0.1 microg kg(-1)), produced reductions of blood pressure,
      accompanied by slight changes (less than 5% except for 100 microg kg(-1)
      adenosine) in heart rate (HR). The vasodepressor responses to VIP and CGRP were
      significantly augmented by i.v. infusion of adenosine (3 microg kg(-1) min(-1)).
      The vasodepressor responses to adenosine and CGRP by VIP (0.03 microg kg(-1) min(
      1)), and those to adenosine and VIP by CGRP (1 ng kg(-1) min(-1)) were also
      enhanced. The response to acetylcholine remained unchanged before and during i.v.
      infusion of either VIP, CGRP or adenosine. The i.v. infusion of cromakalim (0.1
      microg kg(-1) min(-1)) also augmented the responses to VIP, CGRP and adenosine,
      but not to acetylcholine, whereas a single bolus i.v. injection of glibenclamide
      (20 mg kg(-1)) significantly attenuated each one of them. The present results
      suggest that endogenous vasodilators, such as VIP, CGRP and adenosine,
      reciprocally interact in the body, at least partly through ATP-sensitive K+
      channels.

PMID- 9592026
TI  - Role of nitric oxide and free radicals in the contractile response to non
      preactivated leukocytes.
AB  - Previous studies from our laboratory have shown that nitric oxide (NO) can reduce
      the release of free radicals from activated leukocytes. The aim of this study was
      to assess the role of endothelium-derived nitric oxide and leukocyte-derived free
      radicals in the contractile response to non-preactivated leukocytes. Vessel
      tension studies were performed in rabbit endothelium-intact aortic vessel rings
      precontracted with 5-hydroxytryptamine (1 microM). Addition of leukocytes
      isolated from rabbit blood were added to the rings in increasing concentrations
      (10(3)-10(6) cell ml(-1)) under control conditions and in the presence of L
      nitroarginine methyl ester (L-NAME 1 mM), D-NAME (1 mM), or superoxide dismutase
      (100 U ml(-1)). The responses to superoxide radical (generated by xanthine plus
      xanthine oxidase, X/XO), hydrogen peroxide, hypochlorite and peroxynitrite were
      also assessed. The nature of the free radicals released from non-activated
      isolated leukocytes, zymosan-stimulated leukocytes (in whole blood) and isolated
      vessel rings was assessed using luminol-enhanced chemiluminescence. Cumulative
      addition of leukocyte suspensions to aortic rings caused a concentration
      dependent contractile response which was abolished by preincubation of the vessel
      ring with L-NAME. D-NAME and superoxide dismutase were without effect. All the
      free radicals tested produced a relaxation of the precontracted aortic ring. The
      response to X/XO was not affected by superoxide dismutase, but abolished by
      catalase. The responses to hydrogen peroxide and hypochlorite were both found to
      be dependent upon the presence of endothelium and NO. The response to
      peroxynitrite was endothelium-independent and was blocked by methylene blue.
      While the main free radical released from unstimulated leukocytes and vessel
      rings was superoxide, the main radical released from activated leukocytes was
      found to be hypochlorite. These results suggest that the vascular contraction
      seen in response to non-preactivated leukocytes is due to inhibition, by NO, of
      the release of free radicals from the leukocytes when activated by contact with
      the vascular endothelium, thus allowing co-released vasoconstrictor substances to
      exert their effect.

PMID- 9592028
TI  - Monophosphoryl lipid A reduces both arrhythmia severity and infarct size in a rat
      model of ischaemia.
AB  - A non-toxic derivative of the active lipid A component of the endotoxin molecule
      (monophosphoryl lipid A) when given to rats in a dose of 5 mg kg(-1) by
      intraperitoneal injection 24 h prior to anaesthesia and coronary artery
      occlusion, markedly decreased the severity of ischaemia-reduced ventricular
      arrhythmias (ventricular fibrillation reduced from 60 to 21%; P < 0.05) and
      reduced myocardial infarct size (from 35.8 +/- 1.6% of the area at risk to 22.7
      +/- 2.0%; P < 0.05). It did not modify blood pressure or heart rate either before
      or during the period of ischaemia.

PMID- 9592029
TI  - Effects of five different airway smooth muscle relaxants on inhibitory
      neurotransmission in isolated guinea-pig trachea in vitro.
AB  - Pharmacodynamic effects produced by terbutaline (10 nM), theophylline (10
      microM), sodium nitroprusside (30 nM), levcromakalim (0.3 microM) or isradipine
      (1 nM) on frequency-dependent relaxations induced by electric field stimulation
      of either proximal or distal parts of isolated guinea-pig trachea were studied in
      vitro. Preparations were depleted for tachykinins by capsaicin, pretreated with
      atropine (0.1 microM) and contracted by histamine (2 microM). Drug effects were
      studied in preparations with combined adrenergic and inhibitory non-adrenergic
      non-cholinergic (NANC) innervation and in preparations with inhibitory NANC
      innervation either with or without additional treatment with N(G)-nitro-L
      arginine methyl ester (L-NAME) (100 microM). In preparations with combined
      adrenergic and inhibitory NANC innervation terbutaline, sodium nitroprusside,
      levcromakalim and isradipine significantly reduced relaxant responses to electric
      field stimulation in proximal preparations, whereas distal preparations were only
      affected by terbutaline. In preparations with inhibitory NANC innervation without
      L-NAME pretreatment, terbutaline significantly enhanced relaxant responses to
      electric field stimulation only in distal preparations, whereas theophylline,
      sodium nitroprusside and levcromakalim significantly augmented responses to
      electric field stimulation in both proximal and distal preparations. In
      preparations with inhibitory NANC innervation pretreated with L-NAME,
      theophylline significantly inhibited relaxant responses in distal preparations,
      whereas sodium nitroprusside, levcromakalim and isradipine significantly
      augmented relaxant responses to electric field stimulation in proximal
      preparations. It was concluded that drugs used in the present study can modulate
      the effects of inhibitory autonomic and NANC neurotransmission in isolated guinea
      pig trachea. Furthermore, it was shown that some variation in drug effects exists
      in relation to proximal and distal parts of guinea-pig trachea.

PMID- 9592030
TI  - Biochemical and pharmacological characterization of FR134043, a novel elastase
      inhibitor.
AB  - FR134043, disodium(Z,1S,15S,8S,24S,27R,29S,34S,37R)-29-ben zyl-21-ethylidene-27
      hydroxy-15-isobutyrylamino-34-isopropyl-31,37 -dimethyl-10,16,19,22,30,32,35,38
      octaoxo-36-oxa-9,11,17,20,23,28, 31,33
      octaazatetracyclo[16.13.6.1(24),(28).0(3),(8)]octatricont a-3,5,7-trien-5,6-diyl
      disulfate, is a water-soluble inhibitor of human neutrophil elastase with a
      molecular mass of 1166.15 Da. FR134043 demonstrated a characteristic competitive
      inhibition of human neutrophil elastase with a Ki of 8 nM. In studies using
      synthetic substrates, FR134043 inhibited both neutrophil elastase activity and
      porcine pancreatic elastase activity with IC50 values of 35 nM and 49 nM
      respectively. FR134043 also inhibited hydrolysis of bovine neck ligament elastin
      by human neutrophil elastase with an IC50 value of 210 nM. In in vivo
      experiments, FR134043 protected animals against human neutrophil elastase (50
      microg/animal)-induced lung hemorrhage in hamsters with an ED50 value of 3.1
      microg/animal for intratracheal administration and 5.0 mg/kg for intravenous
      administration. Subcutaneous treatment with FR134043 significantly suppressed
      human neutrophil elastase (20 microg/paw)-induced paw edema in mice with an ED50
      value of 3.3 mg/kg when evaluated 4 h after elastase injection. The potency of
      FR134043 given intratracheally to protect against porcine pancreatic elastase
      (100 microg/animal)-induced emphysema in hamsters was relatively low (Quasi
      static lung compliance; ED50 = 1590 microg/animal) compared to that in acute
      animal models. FR134043 (10 mg/kg per h i.v. infusion) significantly improved
      lipopolysaccharide (0.25 mg/kg per h i.v. infusion)-induced thrombocytopenia and
      some coagulation parameters in rats. These results suggest that systemic
      administration of FR134043 would be advantageous over intratracheal
      administration of FR134043 for the treatment of adult respiratory distress
      syndrome, septic shock and pulmonary emphysema and other pathophysiologic
      conditions in which elastases are thought to be involved.

PMID- 9592031
TI  - Inhibition of Ca2+ current in neonatal and adult rat ventricular myocytes by the
      tyrosine kinase inhibitor, genistein.
AB  - Yokoshiki et al. (Yokoshiki, H., Sumii, K., Sperelakis, N., 1996. Inhibition of L
      type calcium current in rat ventricular cells by the tyrosine kinase inhibitor,
      genistein and its inactive analog, daidzein. J. Mol. Cell. Cardiol. 28, 807-814)
      reported that genistein and daidzein inhibited L-type Ca2+ current (I(Ca)(L)) in
      young rat ventricular cells. Therefore, we investigated the developmental
      differences in the effect of genistein, an inhibitor of tyrosine kinases, on
      I(Ca)(L) in freshly-isolated neonatal (3-7 days) and adult (2-5 months) rat
      ventricular myocytes using whole-cell voltage clamp and single-channel recordings
      (cell-attached configuration). For whole-cell voltage clamp, I(Ca)(L) was
      measured as the peak inward current at a test potential of +10 mV by applying a
      300 ms pulse from a holding potential of -40 mV. To isolate I(Ca(L), the pipette
      solution was Cs+-rich and the bath solution was Na+-, K+-free. Ca2+ (1.8 mM) was
      used as charge carrier. Bath application of 100 microM genistein (sufficient for
      maximal effect) decreased the basal I(Ca)(L) by 43.3% (n = 27) in neonatal cells
      and by 30.6% (n = 14) in adult cells (P < 0.05). In the current/voltage
      relationships, the potential of peak I(Ca)(L) was shifted to the right by
      genistein by 8.6 mV in neonatal and by 9.3 mV in adult cells. Genistein produced
      a shift of the steady-state inactivation curve (to the left) in neonatal cells
      (from -16.0 +/- 3.9 mV to -26.1 +/- 4.2 mV; P < 0.05) and in adult cells (-15.9
      +/- 3.2 mV to -22.9 +/- 3.3 mV; P < 0.05); the slope factor was not affected. For
      single-channel recordings in cell-attached patches, Ca2+ currents were evoked by
      applying a 150 ms pulse from a holding potential of -40 mV to a test potential of
      0 mV. The pipette solution contained 110 mM Ba2+ (as charge carrier), and the
      bath solution contained 150 mM K+ (to bring resting potential to near zero).
      Genistein (50 microM) decreased the open probability of the channels from 2.8% to
      0.75% (P < 0.05) in absence of Bay K 8644, and from 24% to 7.9% (P < 0.05) in
      presence of Bay K 8644; the mean open time and the slope conductance of the
      currents were not affected. In conclusion, (1) genistein inhibits the basal
      I(Ca)(L) in rat ventricular cells and (2) the inhibition of I(Ca)(L) by genistein
      is greater in immature cells than in adult cells.

PMID- 9592032
TI  - Anomalous rectifying properties of 'diazepam-insensitive' GABA(A) receptors.
AB  - Studies using recombinant systems indicate that 'diazepam-insensitive' GABA(A)
      receptors in the central nervous system contain alpha4 and alpha6 subunits while
      'diazepam-sensitive' GABA(A) receptors contain alpha1, alpha2, alpha3 and alpha5
      subunits. Both native and recombinant diazepam-sensitive GABA(A) receptors
      typically exhibit large, outwardly rectifying currents. For example, in patch
      clamp studies, Human Embryonic Kidney (HEK) 293 cells transfected with cDNAs
      encoding alpha1beta2gamma2 subunits exhibit a rectification ratio (I +60 mV/I -60
      mV) of 1.95 +/- 0.21. However, anomalous rectification was observed in
      recombinant diazepam-insensitive GABA(A) receptors composed of either
      alpha4beta2gamma2 (rectification ratio, 0.74 +/- 0.09) or alpha6beta2gamma2
      (rectification ratio, 0.67 +/- 0.11) subunits. Based on sequence differences
      between diazepam-sensitive and -insensitive GABA(A) receptor alpha subunits in
      the vicinity of the putative channel lining, a point mutation was introduced at
      His273 on the alpha4 subunit. The rectification ratio in cells expressing a
      mutated alpha4(Asn273)beta2gamma2 receptor increased to 1.92 +/- 0.17. Moreover,
      mutation of the homologous residue in the alpha1 subunit to histidine reduced the
      rectification ratio of alpha1(His274)beta2gamma2 to 1.02 +/- 0.12. The affinities
      of benzodiazepine site ligands at diazepam-sensitive and -insensitive GABA(A)
      receptors were unaffected by these mutations. Thus, the electrophysiological
      properties of diazepam-sensitive and -insensitive GABA(A) receptors may be as
      divergent as their pharmacological characteristics.

PMID- 9592033
TI  - Characterization of neutral endopeptidase in vascular cells, modulation of
      vasoactive peptide levels.
AB  - We characterized neutral endopeptidase activity and protein in the three aortic
      layers and in corresponding cultured primary cells. Neutral endopeptidase was
      expressed in all three layers of rat aorta with higher protein level and activity
      in the adventitia than in the media and intimal endothelium. Neutral
      endopeptidase was also found in primary cultured fibroblasts, smooth muscle and
      endothelial cells derived from the corresponding layers. Neutral endopeptidase
      activity and protein were higher in the fibroblasts and smooth muscle cells than
      in endothelial cells. Neutral endopeptidase inhibition prevented atrial
      natriuretic peptide (ANP) degradation in endothelial and smooth muscle cells. It
      potentiated ANP-stimulated cyclic GMP production in these cells. Neutral
      endopeptidase inhibition also reduced bradykinin degradation and potentiated
      bradykinin-stimulated release of arachidonic acid in fibroblasts and endothelial
      cells. Our data demonstrate the presence and functional activity of neutral
      endopeptidase in all three cell layers of rat aorta as well as in primary cells
      of the vessel. The data suggest that local concentrations of vasoactive peptides
      in the vessel wall might be regulated by the neutral endopeptidase cleavage
      pathway in the immediate vicinity of their target cells.

PMID- 9592034
TI  - Bone resorption induced by A23187 is abolished by indomethacin: implications for
      second messenger utilised by parathyroid hormone.
AB  - Parathyroid hormone acts on the osteoblast to induce osteoclastic bone
      resorption. Parathyroid hormone utilises cyclic AMP as a second messenger in
      osteoblasts, but may also cause an increase in cytoplasmatic free calcium ions
      ([Ca2+]i) in the same cell. To investigate the role of osteoblastic [Ca2+]i in
      the induction of bone resorption, we have compared the effects of parathyroid
      hormone and the Ca2+-ionophore, A23187, as well as the adenylate cyclase
      stimulating agent, forskolin, and the phorbol ester, phorbole 12,13 dibutyrate
      (PDB), on bone resorption in neonatal mouse calvarial bones. Parathyroid hormone
      (0.1 and 1 nM) dose dependently stimulated the release of prelabelled 45Ca2+ in
      72 h culture. Parathyroid hormone-induced bone resorption was not affected by the
      addition of 1 microM indomethacin to the incubation media, and was therefore, not
      mediated by local prostaglandin formation. A23187 stimulated the release of
      45Ca2+ at 1-10 nM. Above 100 nM, A23187 inhibited bone resorption. The A23187 (3
      and 10 nM)-induced bone resorption was abolished by the cyclooxygenase inhibitor,
      indomethacin (1 microM), indicating that the stimulatory effect was mediated via
      prostaglandin formation. The adenylate cyclase stimulating agent, forskolin, dose
      dependently stimulated bone resorption at and above 1 microM. There was no
      additive or synergistic effect of forskolin and A23187 on 45Ca2+ release.
      Forskolin-induced bone resorption was, as with parathyroid hormone but in
      contrast to ionophore-induced bone resorption, not abolished by indomethacin (1
      microM). The protein kinase C activator, PDB, at 10 and 1000 nM stimulated the
      release of prelabelled 45Ca2+. The stimulatory effect of the protein kinase C
      stimulating phorbol ester, PDB, on bone resorption was abolished by the addition
      of indomethacin. In summary, bone resorption induced by a Ca2+-ionophore is
      abolished by indomethacin. This indicates that bone resorbing agents known to
      increase [Ca2+]i subsequently enhance local prostaglandin formation. Bone
      resorption induced by the protein kinase C activator, PDB, was also abolished by
      indomethacin, whereas, forskolin and parathyroid hormone-induced bone resorption
      was unaffected. These data indicate that cyclic AMP, but not [Ca2+]i, is involved
      as a second messenger in parathyroid-induced bone resorption.

PMID- 9592035
TI  - Endothelin ET(B) receptors show different binding profiles in intact cells and
      cell membrane preparations.
AB  - We examined the affinity of endothelin-1, endothelin-3 and four endothelin
      receptor ligands, BQ788 (cis-2,6-dimethylpiperidinocarbonyl-gamma-methyl-Leu-D
      Trp(1-CO 2CH3-D-Nle-ONa), SB-209670 ((+)-(1S,2R,3S)-3-(2-carboxymethoxy-4
      methoxyphenyl)-1-(3,4-methylenedio xyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic
      acid), IRL-1620 (succinyl-[Glu9,Ala11,15]endothelin-1(8-21)), and L-749329 (3',4'
      methylenedioxy-1-(2-propyl-4-carboxyphenoxy)-N-(4-isopropyl -phenylsulfonyl)
      benzene acetamide), for endothelin ET(B) receptors in human and rat heart cells.
      The affinities of these ligands showed good correlation between both types of
      living cells and between their membrane preparations (r = 0.861, P < 0.001), but
      less significant correlation between each of the living cells and its respective
      membrane preparation (r = 0.569, 0.02 < P < 0.05). These results suggest that
      there is no species difference in the affinities of these ligands and that
      destruction of the intact cell membrane structure may lead to changes in binding
      properties of the endothelin ET(B) receptor.

PMID- 9592036
TI  - Update on the monitoring of changes in extracellular glutamate, and their
      significance.

PMID- 9592037
TI  - Opposite roles of D1 and D5 dopamine receptors in locomotion revealed by
      selective antisense oligonucleotides.
AB  - Contralateral rotations induced by the D1-like agonist SKF 38393 in unilaterally
      6-hydroxydopamine-lesioned rats were completely prevented by the administration
      of the D1-like antagonist SCH 23390. A similar result was obtained after
      intracerebroventricular administration of an antisense oligodeoxynucleotide for
      the D1 receptor (D1R-as). Contrariwise, administration of a D5R-as potentiated
      the effects of SKF 38393, showing a 60% increase in the rotational scores. Both
      effects were reversible upon cessation of D1R-as or D5R-as treatment and were
      also specific since rotational scores in rats treated with vehicle or with a
      randomly designed oligodeoxynucleotide were not modified. These results suggest
      that whereas D1 receptors play a facilitatory role in locomotion, D5 receptors
      exert an inhibitory effect.

PMID- 9592038
TI  - Evidence for anatomical specificity for the reinforcing effects of SP in the
      nucleus basalis magnocellularis.
AB  - Previous studies have shown that substance P (SP) exerts reinforcing effects
      following injection into the region of the nucleus basalis magnocellularis (NBM)
      in rats. The aim of the present study was to further characterize this effect by
      examining its anatomical specificity. Reinforcing effects of SP were assessed
      following unilateral microinjection into the NBM or into the nearby rostral part
      of the ventral pallidum (VP), using conditioned place preference as an index for
      reinforcement. Intracranial injection of SP was performed through small diameter
      glass micropipettes which allowed precise delivery of SP in minute quantities. A
      single microinjection of SP (0.2 and 1 ng) into the NBM produced a conditioned
      place preference, whereas injection of SP into the rostral VP failed to alter the
      preference behavior. The results confirm that SP has reinforcing effects when
      administered into the NBM and provide evidence that these effects are brain-site
      specific.

PMID- 9592039
TI  - Critical interval for rescue of axotomized neurons by transplants.
AB  - To determine whether embryonic spinal cord transplants retained the ability to
      prevent retrograde death of Clarke's nucleus (CN) neurons if supplied after a
      delay, we hemisected adult rats at the T8 spinal cord segment and placed
      transplants of fetal tissue into the hemisection cavity immediately or up to 14
      days later. Transplants provided in the first 7 days after injury prevented
      virtually all of the 30% loss of CN neurons at L1 ipsilateral to hemisection that
      occurs without a transplant. Transplants supplied at 14 days post-hemisection
      were ineffective. Because prevention of retrograde neuron death is one mechanism
      by which transplants may contribute to locomotor recovery after spinal cord
      injury, this window of effectiveness should be considered in the design of
      clinical trials.

PMID- 9592041
TI  - No visual responses in denervated V1: high-resolution functional magnetic
      resonance imaging of a blindsight patient.
AB  - Following severe cranio-cerebral trauma that affected the optic radiation,
      patient FS suffers from an incomplete macula-splitting hemianopia. Within the
      hemianopic field, FS exhibits blindsight, i.e. he detects and discriminates
      visual stimuli he cannot (consciously) see. We performed functional magnetic
      resonance imaging (fMRI) at high spatial resolution using a large flickering
      stimulus field to assess visual responsiveness of deafferented V1. Contrasting
      strong activation of the normal contralesional visual cortex, ipsilesional V1
      displayed no stimulus-related MRI signal changes. However, activation was
      observed in ipsilesional extrastriate cortex. We conclude that blindsight does
      not depend on functional islands of tissue preserved within the deafferented
      striate cortex.

PMID- 9592040
TI  - Bax and Bak proteins require caspase activity to trigger apoptosis in sympathetic
      neurons.
AB  - We show that the pro-apoptotic proteins Bax and Bak trigger apoptosis when over
      expressed in sympathetic neurons cultured in the presence of NGF. This effect can
      be blocked with z-VAD-fmk, a peptide inhibitor of caspases, but not with anti
      apoptotic chemical compounds such as antioxidants or proteasome inhibitors. These
      results demonstrate that in sympathetic neurons Bax and Bak are sufficient to
      induce apoptosis in the absence of any other apparent cell death stimulus and
      that their effect is mediated by caspases but does not require reactive oxygen
      species nor activity of the proteasome.

PMID- 9592042
TI  - Differential expression of c-fos and hsp72 mRNA in focal cerebral ischemia of
      mice.
AB  - The heterogeneity of c-fos and hsp72 mRNA expression during focal ischemia was
      studied in mice by combining in situ hybridization with metabolic imaging. Focal
      ischemia was produced by middle cerebral artery occlusion for 3 h. The infarct
      core and the penumbra were differentiated by regional ATP and cerebral protein
      synthesis (CPS) imaging. hsp72 mRNA expression was restricted to the ischemic
      penumbra, as defined by the dissociation between preserved ATP and suppressed
      CPS. c-fos mRNA was expressed not only in the penumbra but also in the peri
      ischemic normal brain tissue in which both ATP and CPS were preserved. These data
      demonstrate a highly selective differential expression of immediate-early and
      stress-related genes in the peri-infarct surrounding which is explained by
      different mechanisms of gene induction.

PMID- 9592043
TI  - Involvement of two isoforms of SNAP-25 in the expression of long-term
      potentiation in the rat hippocampus.
AB  - Induction of long-term potentiation (LTP) in the hippocampus is associated with
      changes in expression of a variety of different proteins and is thought to be the
      mechanism which underlies synaptic plasticity. The 25 kDa synaptosomal-associated
      protein (SNAP-25) is a presynaptic protein which is involved in neurotransmitter
      exocytosis at the nerve terminal. Two isoforms of SNAP-25 have so far been
      identified (a and b) which differ in their distribution and developmental
      regulation. Using in situ hybridization, we demonstrated that the mRNA levels of
      the two isoforms of this protein are increased 2 h after the induction of LTP in
      granule cells of the dentate gyrus following high frequency stimulation of the
      perforant path in vivo. These observations further demonstrate the involvement of
      both isoforms of SNAP-25 in functional synaptic plasticity, although their exact
      roles have yet to be fully determined.

PMID- 9592044
TI  - Cloning of a novel murine isoform of the glial cell line-derived neurotrophic
      factor receptor.
AB  - We report here the cloning of a novel form of the murine glial cell line-derived
      neurotrophic factor (GDNF) receptor. Northern blot analyses of various mouse
      tissues, including whole brain, demonstrated the existence of multiple
      transcripts of GDNF receptor. Screening of an adult mouse liver cDNA library
      yielded two isoforms of the receptor. One of the forms (alpha) shows a high
      degree of homology with other mammalian GDNFR-alpha and the other novel form
      (beta) is identical to the alpha form except for a deletion of five amino acids.
      These two forms do not share high sequence homologies with the recently isolated
      neurturin receptor. Both the alpha and beta forms are expressed in various murine
      tissues but not in muscle.

PMID- 9592046
TI  - Postural control, attention and sleep deprivation.
AB  - We investigated the effect of sleep deprivation on postural control during a
      simple reaction time task (SRT), during a task requiring the intermittent
      inhibition of a reaction (IRT), and in the absence of a concurrent information
      processing task. Postural sway, i.e. changes in center of pressure on a force
      platform, was recorded in three increasingly difficult standing conditions (fixed
      platform, sway-referenced platform and sway-referenced platform with sway
      referenced visual scene) during the three information-processing task conditions.
      Five healthy subjects performed the tasks either after normal sleep or following
      24 h of sustained wakefulness. As hypothesized, sleep deprivation significantly
      increased postural sway only in the IRT condition. Within the IRT condition,
      sleep deprivation significantly increased sway across all postural conditions.

PMID- 9592045
TI  - GDNF and its receptor component Ret in injured human nerves and dorsal root
      ganglia.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is trophic to motor and
      sensory neurones in animal models. GDNF mRNA is up-regulated in Schwann cells
      after peripheral nerve injury in rats. We have quantified and localized GDNF and
      its receptor component Ret, for the first time in any species, in injured human
      peripheral nerves and dorsal root ganglia (DRG) avulsed from the spinal cord.
      Significantly higher levels of GDNF were found in nerve distal to the site of the
      injury than in proximal or intact nerve, and in avulsed DRG than in post-mortem
      control DRG. GDNF immunostaining was seen in Schwann cells and in DRG neurones,
      especially of small and medium size, with significantly increased numbers of
      medium sized sensory neurones immunoreactive for GDNF after avulsion. Ret
      immunoreactivity was restricted to DRG neurones and axons, with no significant
      changes in numbers of positive DRG cells after injury. Our findings suggest that
      GDNF may play a role in injured human nerves and sensory ganglia, particularly in
      medium sized sensory neurones.

PMID- 9592047
TI  - Evaluation of endozepine-like immunoreactivity in the frontal cortex of suicide
      victims.
AB  - Diazepam-binding inhibitor (DBI) and its processing products, including the
      octadecaneuropeptide (ODN), are polypeptides called endozepines which have
      multiple biological effects, including regulation of mitochondrial
      steroidogenesis and modulation of GABA-gated chloride channels. Concentrations of
      ODN-like immunoreactivity (ODN-Li) were measured by radioimmunoassay in the
      frontal cortex of nine drug-free suicides and nine drug-free sudden-death
      victims. The level of ODN-Li was higher in the right than in the left frontal
      cortex, in both suicide (p < 0.05) and control (p < 0.02) subjects. No
      significant differences were found between suicides and controls either in the
      right and left cortex, or when considering the gender and the post-mortem
      diagnosis of depression.

PMID- 9592048
TI  - A novel effect of nicotine on mood and sleep in major depression.
AB  - The role of repeated nicotine administration on sleep and major depression was
      studied. Six non-smoking normal volunteers (NV) and six non-smoking major
      depressed patients (MD) with a Hamilton Rating Scale for Depression > 18 served
      as subjects. All subjects underwent the following sleep procedures:
      acclimatization, control night, four nicotine nights (17.5 mg, transdermal
      patches) and one withdrawal night (WN). Nicotine increased REM sleep time in both
      groups and also on the WN. Hamilton scores showed an average reduction of 43.9%
      in the depressed patients. These findings suggest that nicotine receptor
      activation may be important in major depression and shows for the first time that
      nicotine patches may be useful in the treatment of depression.

PMID- 9592049
TI  - Pharmacological characterization and differentiation of non-cholinergic nucleus
      basalis neurons in vitro.
AB  - Using intracellular recordings in guinea pig brain slices, the pharmacology of
      electrophysiologically identified and immunohistochemically confirmed non
      cholinergic nucleus basalis neurons was studied to determine their response to
      the major neurotransmitters of the subcortical afferents to this region. The
      cells were differentiated into three types: Type A cells (approximately 44%) were
      depolarized by noradrenaline (NA) and muscarine, Type B cells (approximately 23%)
      were depolarized by NA but hyperpolarized by muscarine, and Type C cells
      (approximately 15%) were hyperpolarized by both agonists. These cell types were
      also differentially responsive to serotonin (hyperpolarizing B, C) and histamine
      (depolarizing A, B). Accordingly, the non-cholinergic neurons share certain
      discharge properties but appear nonetheless to comprise distinct types which
      respond differentially to the major modulatory neurotransmitters and thus play
      potentially different roles in cortical modulation across the sleep-wake cycle.

PMID- 9592050
TI  - Tau complexes with phospholipase C-gamma in situ.
AB  - Based on the results of recent in vitro studies, tau has been proposed to be
      involved in regulating signal transduction through the phospholipase C-gamma (PLC
      gamma) signaling pathway. The present study provides support for the
      physiological relevance of this hypothesis by demonstrating the existence of a
      tau-PLC-gamma complex in situ in a human neuroblastoma cell line. Both PLC-gamma
      and PLC-delta, but not PLC-beta, co-purified with microtubule-associated
      proteins. PLC-gamma, but neither PLC-delta nor PLC-beta, co-immunoprecipitated
      with tau, and the PLC co-precipitating with tau was enzymatically active.
      Additionally, both tau and MAP-2 co-precipitated with PLC-gamma. These studies
      indicate that tau associates, either directly or indirectly, with PLC-gamma in
      situ, suggesting that tau may be appropriately localized to participate in the
      regulation of signal transduction through the PLC-gamma pathway in vivo.

PMID- 9592051
TI  - Acute and repeated ECS treatment increases CRF, POMC and PENK gene expression in
      selected regions of the rat hypothalamus.
AB  - The purpose of this study was to investigate the effects of acute and repeated
      electroconvulsive shock (ECS) on corticotropin releasing factor (CRF),
      proopiomelanocortin (POMC) and proenkephalin (PENK) gene expression in selected
      regions of the brain and pituitary of the rat. Acute ECS increased CRF gene
      expression in the paraventricular nucleus (PVN) by 20%, an effect that was
      further enhanced to 38% when rats received repeated ECS treatment. Acute and
      repeated ECS increased POMC gene expression in the arcuate nucleus (ARC) by 49
      59% but failed to alter these mRNA levels in the anterior lobe (AL) of the
      pituitary gland. PENK gene expression was increased by 35% in the nucleus
      accumbens (NA) and by 180% the ventromedial nucleus (VMN) after acute or repeated
      ECS treatment but no significant changes were found in the PVN or striatum (ST).
      Taken together, these results indicate a differential CRF and opioid gene
      expression regulation after acute or repeated ECS treatment that may be relevant
      to their therapeutic or side effects in depression.

PMID- 9592052
TI  - Alterations of metallothionein II and apolipoprotein J mRNA levels in kainate
      treated rats.
AB  - Although different mechanisms have been proposed, it has been suggested that
      apolipoprotein J (ApoJ) and metallothionein II (MTII), expressed by astrocytes,
      are protective proteins. Alterations in their expression may contribute to the
      involvement of astrocytes in epileptogenesis. We studied the expression of MTII
      and ApoJ genes 7 days following status epilepticus induced in rats by intra
      amygdala injection of kainate (KA). ApoJ mRNA levels were increased in both
      cortex (77%, p < 0.01) and hippocampus (64%, p < 0.02), whereas, in contrast to
      previous findings 3 days after KA injection, DNA fragmentation was not detected
      on agarose gel electrophoresis. These results show that ApoJ is induced along
      with early genes during massive apoptosis, and remains induced after the acute
      phase. MTII mRNA levels were altered only in hippocampus (62%, p < 0.05), whereas
      KA-treated rats had no seizure for 7 days. The sustained induction of MTII mRNA
      shows that zinc homeostasis is not returned to normal or alternatively that
      astrocytes maintain an altered phenotype in spite of normal zinc release.
      Polyadenylated RNA and beta-actin mRNA levels were in contrast unaltered in
      cortex or hippocampus at this time point. These specific variations in ApoJ and
      MTII mRNA expression during the latent period suggest that they are part of long
      term biochemical and/or phenotypic alterations in astrocytes, following a single
      episode of severe seizures.

PMID- 9592053
TI  - Neural activity in areas V1, V2 and V4 during free viewing of natural scenes
      compared to controlled viewing.
AB  - Under natural viewing conditions primates make frequent exploratory eye movements
      across complex scenes. We recorded neural activity of 62 cells in visual areas
      V1, V2 and V4 in an awake behaving monkey that freely viewed natural images.
      About half of the cells studied showed a modulation in firing rate following some
      of the eye movements made during free viewing, though the proportions showing a
      discernible modulation varied across areas. These cells were also examined under
      controlled viewing conditions in which gratings or natural image patches were
      flashed in and around the classical receptive field while the animal performed a
      fixation task. Activity rates were generally highest with flashed gratings and
      lowest during free viewing. Flashed natural image patches evoked responses
      between these two extremes, and the responses were higher when the patches were
      confined to the classical receptive field than when they extended into the non
      classical surround. Thus the reduction of activity during free viewing relative
      to that obtained with flashed gratings is partly attributable to natural images
      being less effective stimuli and partly to suppressive spatio-temporal neural
      mechanisms that are important during natural vision.

PMID- 9592054
TI  - Peri-threshold encoding of stimulus frequency and intensity in the M100 latency.
AB  - Recent work has suggested that, in addition to spatial tonotopy, pitch and timbre
      information may be encoded in the temporal activity of the auditory cortex.
      Specifically, the post-stimulus latency of the maximal cortical evoked
      neuromagnetic field (M100 or N1m) is a function of stimulus frequency. We
      investigated the additional effect of varying the stimulus intensity on the M100
      response. A 37-channel biomagnetometer recorded neuromagnetic fields over the
      temporal lobe of healthy volunteers in response to monaurally presented tones.
      The frequency dependence of the M100 latency remained remarkably invariant even
      at low stimulus intensity. Thus, for peri-threshold stimuli, frequency
      information appears encoded in the temporal form of the evoked response.

PMID- 9592055
TI  - Evidence that brain mast cells can modulate neuroinflammatory responses by tumour
      necrosis factor-alpha production.
AB  - Tumour necrosis factor-alpha (TNF-alpha) levels in mammalian brain increase
      during neuroinflammatory diseases. We used the competitive polymerase chain
      reaction (PCR) to quantify the amount of TNF-alpha in stimulated and unstimulated
      brain mast cells (BMC). A cDNA fragment shortened by a deletion of 56 bp was used
      as an internal TNF-alpha-specific standard. The immunological stimulus resulted
      in enhanced TNF-alpha mRNA expression and increased release of histamine and TNF
      alpha. This is the first time that BMC showing functional FCepsilonRI-bound IgE
      receptors have been purified. Our results support the hypothesis that BMC
      mediators might induce an initial response in neuroinflammatory diseases.

PMID- 9592056
TI  - Inhibition of phospholipase C blocks opioid receptor-mediated activation of Gi
      proteins.
AB  - Activation of phospholipase C (PLC) in response to stimulation of delta-opioid,
      m4 muscarinic and alpha2 adrenergic receptors was observed in NG108-15 cells.
      Treatment with PLC specific inhibitors, U73122 and ET-18-OCH3, blocked delta
      opioid receptor-mediated activation of G proteins with no effect on opioid
      binding to the receptors. U73122 treatment also suppressed functional responses
      of m4 muscarinic and alpha2 adrenergic receptors in NG108-15 cells. Furthermore,
      the G protein activation mediated by mu- and delta-opioid receptors and opioid
      receptor-like receptor (ORL1) were abolished by U73122 in SK-N-SH neuroblastoma
      cells. Inhibition of adenylyl cyclase induced by high concentrations of GTP was
      blocked by U73122, suggesting that blockade is at the level of G proteins. Our
      results thus indicated that inhibition of PLC leads to blockade of Gi protein
      activation mediated by opioid receptors or other Gi-coupled receptors.

PMID- 9592057
TI  - Is there semantic specificity in overlapping-figures agnosia?
AB  - A case of apperceptive visual agnosia, revealing difficulties only in the
      performance on a standard overlapping-figures test, has been studied. Unusually,
      the patient demonstrated difficulties only with two semantic categories of the
      overlapped figures (clothes and school accessories); preserving, however, the
      knowledge of the same figures when presented isolated. We propose that the
      underlying deficit is only of a pseudo-semantic nature and is actually due to
      certain similarities of the two overlapping combinations, creating difficulties
      still on the apperception level only.

PMID- 9592058
TI  - Noribogaine stimulates naloxone-sensitive [35S]GTPgammaS binding.
AB  - Noribogaine is formed in vivo by the O-demethylation of the indole alkaloid
      ibogaine. We report here that noribogaine acts as a full agonist at the mu-opioid
      receptor. Noribogaine-stimulated guanylyl 5'gamma-[35S]thio]triphosphate
      ([35S]GTPgammaS) was studied in rat thalamic membranes to measure activation of
      guanine nucleotide binding proteins (G-proteins) in the presence of excess GDP.
      Noribogaine caused a 170% increase above basal [35S]GTPgammaS binding at sub
      micromolar effective concentrations (EC50) in a naloxone-sensitive manner,
      confirming that this effect was an opioid receptor-mediated process. The level of
      intrinsic activity for noribogaine in these assays was comparable to the full
      agonists DAMGO and morphine. In contrast, ibogaine had no significant effect on
      [35S]GTPgammaS binding over a similar concentration range. The efficacy of
      noribogaine as a full mu-opioid agonist may explain ibogaine's ability to block
      the acute signs of opiate withdrawal and its suppressive effects on morphine self
      administration.

PMID- 9592059
TI  - Glucose uptake by C6 glioma cells is mediated by G(q alpha).
AB  - The role of G proteins in glucose uptake was investigated using C6 glioma cells.
      Carbachol (an agonist acting via G protein coupled receptors) and 5'
      guanylylimidodiphosphate (Gpp(NH)p; a nonhydrolysable guanine nucleotide analog
      which bypasses the receptors and directly activates G proteins) stimulated [3H]2
      deoxy-D-glucose (2DG) uptake by C6 cells, suggesting that hexose uptake is a G
      protein-mediated process. To identify the G protein involved in glucose uptake by
      C6 cells, the effect of carbachol on 2DG uptake was examined in the presence of
      pertussis toxin. Pertussis toxin treatment did not alter the ability of C6 cells
      to respond to carbachol, ruling out the involvement of G(i alpha) in 2DG uptake.
      C6 cells were transfected with G(q alpha) or GLUT1 cDNA for 48 h, exposed to 1 mM
      carbachol for 2 h, and processed for 2DG uptake. Carbachol stimulated 2DG uptake
      in both G(q alpha) and GLUT1-transfected cells. Gpp(NH)p, also stimulated 2DG
      uptake in G(q alpha) and GLUT1-transfected cells. These results suggest that
      muscarinic receptor coupling to G(q alpha) regulates hexose uptake in C6 cells.

PMID- 9592060
TI  - Functional neuroimaging of attention in the auditory modality.
AB  - Previous functional neuroimaging studies of attention have emphasized the visual
      modality. We developed an auditory version of the continuous performance test
      (CPT) that included simple, focused and divided attention conditions. Positron
      emission tomographic (PET) scans were acquired during CPT performance in normal
      young adults and then submitted to statistical parametric mapping. Simple
      attention brought about a large region of activation involving the anterior
      cingulate gyrus and the right anterior/mesial frontal lobe. Focused and divided
      attention CPT conditions were compared but there were few significant
      differences. The findings are consistent with activation of an anterior attention
      network during auditory attention, without involvement of posterior attention
      structures which are more likely to vary in accordance with sensory modality.

PMID- 9592061
TI  - Complex dendritic fields of pyramidal cells in the frontal eye field of the
      macaque monkey: comparison with parietal areas 7a and LIP.
AB  - Layer III pyramidal neurones were injected with Lucifer Yellow in cortical slices
      taken from the medial subdivision of the frontal eye field (FEF) of the macaque
      monkey. The average area covered by basal dendritic fields, in the dimension
      parallel to the cortical layers, was 115.1 +/- 2.9 x 10(3) microm2, significantly
      larger than that observed among layer III cells in eye movement-related visual
      areas of the parietal lobe. Furthermore, the dendritic fields of pyramidal cells
      in the FEF were considerably more complex than those of their counterparts in the
      parietal lobe, as evaluated by Sholl analysis. Spine density varied along the
      basal dendritic tree, reaching a maximum of 8.5 +/- 0.8 spines/10 microm at a
      distance of 70-90 microm from the centre of the cell body. Such highly complex
      basal dendritic fields of layer III pyramidal neurones in the FEF may enable the
      integration of a diverse set of inputs from visual, motor, polysensory and memory
      related periprincipal cortical areas.

PMID- 9592062
TI  - Chronic neuroleptic treatment alters expression of glial glutamate transporter
      GLT-1 mRNA in the striatum.
AB  - Recent reports have shown that typical neuroleptics may enhance glutamatergic
      neurotransmission and that these effects might in part underlie motor side
      effects of chronic neuroleptic treatment. Since glutamate reuptake is the primary
      mechanism for controlling extracellular glutamate levels, the present study was
      conducted to examine whether chronic neuroleptic exposure alters gene expression
      for the glutamate transporter GLT-1 in the striatum. Although both haloperidol
      and clozapine treatment for 30 days significantly decreased GLT-1 expression from
      normal, the effects of haloperidol treatment were consistently, and in the dorsal
      striatum, significantly greater than those of clozapine. These findings suggest
      that a deficiency in glutamate transport may underlie the pathogenesis of
      neuroleptic-induced movement disorders.

PMID- 9592063
TI  - Circadian release of amino acids in the suprachiasmatic nucleus in vitro.
AB  - Temporal patterns of release of aspartate, glutamate and glycine, which are
      related to excitatory amino acidergic transmission, were examined in organotypic
      slice cultures of rat suprachiasmatic nucleus over a 60 h period. Vasopressin
      release in the same culture was measured simultaneously to compare the temporal
      pattern with that of the amino acids. Amino acids and vasopressin were measured
      by high performance liquid chromatography and enzyme immunoassay, respectively.
      Robust circadian rhythms were detected in release of aspartate, glutamate and
      glycine. Glycine levels were about 10 times higher than those of aspartate and
      glutamate in the culture. Vasopressin also showed a clear circadian rhythm and
      the phase angle difference between each amino acid and AVP was not significantly
      different. The results indicate that cultured SCN cells release these amino acids
      and the release is under the control of the circadian pacemaker.

PMID- 9592064
TI  - Cystic fibrosis transmembrane conductance regulator expression in human
      hypothalamus.
AB  - We have previously characterized the expression of the cystic fibrosis
      transmembrane conductance regulator protein (CFTR) gene, mRNA and protein in rat
      brain with reverse transcriptase (RT)-PCR amplification, in situ hybridization
      and immunocytochemistry. We now report that the CFTR mRNA is expressed in the
      human anterior hypothalamus, an area involved in regulation of appetite, resting
      energy expenditure and sexual differentiation. Expression of CFTR in neurons
      localized to this region may elucidate the pathogenesis of other non-pulmonary
      manifestations of cystic fibrosis which commonly are observed in children with
      CF, including congenital absence of the vas deferens. Neuron-specific expression
      of CFTR in brain may be involved in the regulation of homeostatic functions
      including reproductive function and fertility through effects on neurosecretion,
      i.e. GnRH release. Dysregulation of normal neuropeptide vesicle trafficking by
      mutant CFTR in brain my lead to alteration in physiological function.

PMID- 9592065
TI  - Eye enucleation alters intracellular distribution of NO synthase in the superior
      colliculus.
AB  - We investigated the role of retinotectal projections on the distribution of
      nitric oxide synthase (NOS) in the retinoceptive layers of the rat superior
      colliculus (SC) using histochemical methods. Rats enucleated at birth showed no
      alteration in the temporal pattern of NOS expression. There was, however, a
      dramatic change in the NADPH-diaphorase staining pattern of NOS-positive cells.
      NOS was absent from the distal portions of the dendritic trees of the
      deafferented SC. Nevertheless, staining the dendritic trees of these cells with
      Lucifer yellow showed that they were not morphologically different from those of
      the ipsilateral SC of monoenucleated animals. The same results were obtained when
      enucleation was performed in adult rats. We conclude that NOS intracellular
      distribution in the SC cells can be regulated by retinotectal projections in both
      developing and adult animals.

PMID- 9592067
TI  - Retrograde transport of nerve growth factor from olfactory bulb to olfactory
      epithelium.
AB  - NGF is produced in the olfactory bulb and transported from the bulb to
      cholinergic neurons in the horizontal limb of the diagonal band. Although the
      expression of NGF receptors has been reported in olfactory epithelial cells, no
      correlation between NGF and olfactory epithelial cells has been found. This study
      aimed to define whether or not retrograde transport of NGF occurs in the
      olfactory neural system using the method of radioluminography. 125I-labeled NGF
      injected into the olfactory bulb was taken up and transported to the olfactory
      epithelium 18 h after injection. This finding suggests that bulbar NGF may act as
      a neurotrophic factor in olfactory epithelial cells.

PMID- 9592066
TI  - L-arginine produces NO-independent increases in dopamine efflux in rat striatum.
AB  - The effect of L-arginine (L-ARG; 10-100 mM) on dopamine efflux from rat striatum
      was investigated using in vivo microdialysis. L-ARG (50 mM-100 mM), but not D
      arginine (100 mM) nor L-citrulline (100 mM), produced a biphasic effect on
      dopamine efflux with an initial small reduction, followed by a large sustained
      increase. The effect of L-ARG was not prevented by nitric oxide synthase
      inhibition with NG-nitro-L-arginine methyl ester or 7-nitroindazole monosodium
      salt. Efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid
      (HVA) was reduced by L-ARG (10-100 mM), D-arginine (100 mM) and L-citrulline (100
      mM). These data suggest that changes in dopamine, DOPAC and HVA efflux produced
      by high concentrations of L-ARG occur independently of NO, and that the use of
      high L-ARG concentrations are inappropriate when investigating the role of NO in
      striatum.

PMID- 9592068
TI  - EEG slowing and cerebrospinal fluid tau levels in patients with cognitive
      decline.
AB  - We explored the relationship between cerebrospinal fluid (CSF) tau levels as
      indirect markers of tau-related pathology in Alzheimer's disease (AD) and EEG
      slowing, a typical neurophysiological finding in the disease. A positive
      correlation between CSF tau levels and ratio of alpha/delta global field power
      was found in 14 AD patients (r = 0.65, p = 0.01). This relationship was better
      approximated by polynomial fit of 2nd degree (p = 0.002). A subgroup of AD
      patients (n = 7) with higher tau levels and shorter duration of illness showed a
      strong relationship between CSF tau levels and alpha/theta (r = 0.83, p = 0.02),
      and alpha/delta (r = 0.87, p = 0.01) ratios of the global field power. There were
      no significant correlations between EEG slowing and CSF tau levels in 12 patients
      with mild cognitive dysfunction or in 14 healthy control subjects. That a strong
      inverse linear correlation exists in AD patients with higher levels of tau and
      shorter duration of illness may imply that with longer illness duration CSF tau
      levels decrease due to neuronal death.

PMID- 9592069
TI  - Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral
      impairment.
AB  - Chronic reductions in cerebral blood flow associated with aging and progressive
      neurodegenerative disorders can precipitate cognitive failure. To assess whether
      chronic cerebrovascular insufficiency elicits neuronal apoptosis, apoptotic cell
      death in the hippocampus was quantitated in a rat model of permanent carotid
      occlusion. Bilateral carotid artery occlusion (2VO) was shown to induce apoptotic
      morphology and DNA strand breaks in hippocampal neurons 2 and 27 weeks after
      ligation. The rate of pyramidal cell apoptosis was higher at chronic (27 weeks)
      compared to sub-chronic (2 weeks) time points. 2VO-induced apoptosis resulted in
      a decrease in total pyramidal cell number at 27 weeks but not at earlier time
      points, indicating progressive neuronal loss. Working and reference memory errors
      in the radial arm maze were strongly correlated with the number of apoptotic
      neurons in CA1 but not CA3 pyramidal cell fields. These data provide the first
      indication that apoptotic loss of pyramidal neurons may play a role in memory
      impairment associated with clinical conditions of chronic cerebrovascular
      insufficiency.

PMID- 9592070
TI  - CO2-sensitive medullary neurons: activation by intracellular acidification.
AB  - Bioelectric activity of CO2-sensitive, ventrolateral medullary neurons (VLN(CS))
      in organotypic cultures from the obex level of newborn rats was tested during
      changes of the intracellular pH (pHi) measured in BCECF-AM loaded cultures.
      Hypercapnia (pCO2 80-100 mmHg) reduced pHi by 0.15 +/- 0.06 units and stimulated
      neuronal discharges. Replacement of CO2/HCO3- in the bath by HEPES (26 mM, pH
      7.4) for 10 min acidified pHi (0.07 +/- 0.03 units) and also excited VLN(CS).
      Ammonium chloride (10 mM, 1 min) initially alkalized (0.1 +/- 0.04) and
      thereafter acidified pHi (0.06 +/- 0.03), while the extracellular pH was first
      acidified and then alkalized. This resulted in neuronal discharge which were
      first suppressed and then accelerated. The findings strongly suggest that
      intracellular rather than extracellular acidification activates CO2-sensitive
      neurons.

PMID- 9592071
TI  - Phenserine, a novel acetylcholinesterase inhibitor, attenuates impaired learning
      of rats in a 14-unit T-maze induced by blockade of the N-methyl-D-aspartate
      receptor.
AB  - The present study evaluated the interaction of the glutamatergic and
      acetylcholinergic systems in memory formation, with an overall emphasis on
      developing multi-system approaches for treating age-related cognitive decline and
      Alzheimer' s disease. Specifically, we used a 14-unit T-maze to investigate
      whether phenserine (PHEN), a long-acting acetylcholinesterase inhibitor, could
      overcome a learning deficit in rats induced by the NMDA receptor antagonist, 3
      (+/-) 2-carboxypiperzin-4-yl) propyl phosphonic acid (CPP). Prior to drug
      treatment, 3-month-old male Fischer-344 rats were trained to criterion (13 of 15
      shock avoidances) in a straight runway. Twenty-four hours later, rats were given
      i.p. injections of saline (SAL), CPP (9 mg/kg) + SAL or CPP + PHEN (0.25, 0.5 or
      0.75 mg/kg) and received 15 massed training trials in a 14-unit T-maze. CPP
      significantly increased the number of errors made in the maze relative to
      controls, and phenserine significantly reduced the number of errors made relative
      to rats receiving CPP only, with the lowest dose being the most effective. These
      results provide further support of phenserine's potent, cognitive-enhancing
      properties, and suggest that combined modulation of glutamatergic and
      acetylcholinergic systems may be of potential benefit in developing new
      pharmacotherapies for Alzheimer's disease and age-related cognitive decline.

PMID- 9592072
TI  - Regulation of chloride channels in secretory epithelia.
AB  - Fluid and electrolyte secretion from secretory epithelia is a highly regulated
      process. Chloride channel activity at the apical membrane determines the rate and
      direction of salt and water secretion. Multiple classes of Cl- channels with
      distinct gating mechanisms are involved in moving ions and water. Secretory
      agonists that induce intracellular increases in two second messenger systems,
      cAMP and [Ca2+]i, are generally associated with secretion. However, changes in
      cell volume and the membrane potential may also play a role in regulating fluid
      and electrolyte secretion in some tissues. In this review we discuss the
      regulation of the different types of Cl- channels found in secretory epithelia.

PMID- 9592073
TI  - Comparison of voltage-activated Cl- channels in rat parotid acinar cells with ClC
      2 in a mammalian expression system.
AB  - Rat parotid acinar cells express Cl- currents that are activated in a time
      dependent manner by hyperpolarized potentials. ClC-2, a member of the ClC gene
      family, codes for a voltage-gated, inward rectifying anion channel when expressed
      in Xenopus oocytes. In the present study, we found that cDNA derived from
      individual parotid acinar cells contained sequence identical to that reported for
      ClC-2 in rat brain and heart. A polyclonal antibody generated against the N
      terminal cytoplasmic domain of ClC-2 recognized an approximately 100 kD protein
      on western blots of both brain and parotid gland. ClC-2 expressed in oocytes has
      different kinetics from the currents found in parotid acinar cells. Since the ClC
      2 channel was cloned from and its transcripts are expressed in mammalian tissue,
      we compared the channel properties of acinar cells to a mammalian expression
      system. We expressed ClC-2 channels in human embryonic kidney cells, HEK 293,
      using recombinant ClC-2 DNA and ClC-2 DNA fused with DNA coding for jellyfish
      green fluorescent protein (GFP). Confocal microscopy revealed that the expressed
      ClC-2-GFP chimera protein localized to the plasma membrane. Whole cell Cl-
      currents from HEK 293 cells expressing ClC-2-GFP were similar, if not identical,
      to the Cl- currents recorded from cells transfected with ClC-2 cDNA (no GFP). The
      voltage-dependence and kinetics of ClC-2 channels expressed in HEK 293 cells were
      quite similar to those in acinar cells. Channels in parotid acinar and HEK 293
      cells activated at more positive membrane potentials and with a faster time
      course than the channels expressed in Xenopus oocytes. In summary, we found that
      ClC-2 message and protein are expressed in salivary cells and that the properties
      of voltage-activated, inward rectifying Cl- channels in acinar cells are similar
      to those generated by the ClC-2-GFP construct expressed in HEK 293 cells. The
      properties of the ClC-2 anion channel seem to be dependent on the type of cell
      background in which it is expressed.

PMID- 9592074
TI  - Separate swelling- and Ca2+-activated anion currents in Ehrlich ascites tumor
      cells.
AB  - A Ca2+-activated (ICl,Ca) and a swelling-activated anion current (ICl,vol) were
      investigated in Ehrlich ascites tumor cells using the whole cell patch clamp
      technique. Large, outwardly rectifying currents were activated by an increase in
      the free intracellular calcium concentration ([Ca2+]i), or by hypotonic exposure
      of the cells, respectively. The reversal potential of both currents was dependent
      on the extracellular Cl- concentration. ICl,Ca current density increased with
      increasing [Ca2+]i, and this current was abolished by lowering [Ca2+]i to <1 nm
      using 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA). In
      contrast, activation of ICl,vol did not require an increase in [Ca2+]i. The
      kinetics of ICl,Ca and ICl,vol were different: at depolarized potentials, ICl,Ca
      as activated in a [Ca2+]i- and voltage-dependent manner, while at hyperpolarized
      potentials, the current was deactivated. In contrast, ICl,vol exhibited time- and
      voltage-dependent deactivation at depolarized potentials and reactivation at
      hyperpolarized potentials. The deactivation of ICl, vol was dependent on the
      extracellular Mg2+ concentration. The anion permeability sequence for both
      currents was I- > Cl- > gluconate. ICl,Ca was inhibited by niflumic acid (100
      micron), 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 100 micron) and 4, 4'
      diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS, 100 micron), niflumic acid
      being the most potent inhibitor. In contrast, ICl,vol was unaffected by niflumic
      acid (100 micron), but abolished by tamoxifen (10 micron). Thus, in Ehrlich
      cells, separate chloride currents, ICl,Ca and ICl,vol, are activated by an
      increase in [Ca2+]i and by cell swelling, respectively.

PMID- 9592075
TI  - Dimensions of neuronal nicotinic acetylcholine receptor channel as estimated from
      the analysis of the channel-blocking effects.
AB  - Acetylcholine-induced membrane currents and excitatory postsynaptic currents
      (EPSCs) were recorded from the neurons of rat superior cervical ganglion (SCG)
      using the whole-cell patch clamp and the two-electrode voltage clamp techniques,
      correspondingly. The EPSC decay was bi-exponential, with fast and slow components
      characterized by time constants 5.5 +/- 0.5 msec and 20.4 +/- 1.2 msec (mean +/-
      SEM; n = 23), respectively. Blocking of these currents by a series of newly
      synthesized bis-cationic ammonium compounds, the pentamethonium and pentaethonium
      derivatives, was analyzed. Blocking effects were due to a block of nicotinic
      acetylcholine receptor (nAChR) open channel, with mean blocker binding rate
      constants for the fast component three to five times higher than those for the
      slow component. Dimensions of a nAChR ionic channel were deduced from a
      relationship between blocking activity of the compounds and the size of the
      projections of their three-dimensional molecular models on the neuronal membrane
      plane. The results suggest that there are two populations of nAChRs in rat SCG
      neurons; while these polulations differ in the rate constants of the binding by
      the blocker to their open channels, they exhibit similar channel diameter, 11.8
      A, at the level at which the blockers bind to the channel.

PMID- 9592076
TI  - Functional expression of p64, an intracellular chloride channel protein.
AB  - p64 is a protein identified as a chloride channel by biochemical purification
      from kidney microsomes. We expressed p64 in HeLa cells using a recombinant
      vaccinia virus/T7 RNA polymerase driven system. Total cell membranes were
      prepared from infected/transfected cells and fused to a planar lipid bilayer. A
      novel chloride channel activity was found in cells expressing p64 and not in
      control cells. The p64-associated activity shows strong anion over cation
      selectivity. Single channels show prominent outward rectification with single
      channel conductance at positive potentials of 42 pS. The chloride channel
      activity is activated by treatment of the membranes with alkaline phosphatase and
      inhibited by DNDS and by TS-TM calix(4)arene. Whole membrane anion permeability
      was determined by a chloride efflux assay, revealing that membranes from cells
      expressing p64 showed a small but highly significant increase in chloride
      permeability, consistent with expression of a novel chloride channel activity.

PMID- 9592077
TI  - ATP-Induced shape change of nuclear pores visualized with the atomic force
      microscope.
AB  - Bidirectional transport of molecules between nucleus and cytoplasm through the
      nuclear pore complexes (NPCs) spanning the nuclear envelope plays a fundamental
      role in cell function and metabolism. Nuclear import of macromolecules is a two
      step process involving initial recognition of targeting signals, docking to the
      pore and energy-driven translocation. ATP depletion inhibits the translocation
      step. The mechanism of translocation itself and the conformational changes of the
      NPC components that occur during macromolecular transport, are still unclear. The
      present study investigates the effect of ATP on nuclear pore conformation in
      isolated nuclear envelopes from Xenopus laevis oocytes using the atomic force
      microscope. All experiments were conducted in a saline solution mimicking the
      cytosol using unfixed nuclear envelopes. ATP (1 mM) was added during the scanning
      procedure and the resultant conformational changes of the NPCs were directly
      monitored. Images of the same nuclear pores recorded before and during ATP
      exposure revealed dramatic conformational changes of NPCs subsequent to the
      addition of ATP. The height of the pores protruding from the cytoplasmic surface
      of the nuclear envelope visibly increased while the diameter of the pore opening
      decreased. The observed changes occurred within minutes and were transient. The
      slow-hydrolyzing ATP analogue, ATP-gamma-S, in equimolar concentrations did not
      exert any effects. The ATP-induced shape change could represent a nuclear pore
      "contraction."

PMID- 9592078
TI  - H+ ATPase and Cl- interaction in regulation of MDCK cell pH.
AB  - MDCK cells display several acid-base transport systems found in intercalated
      cells, such as Na+-H+ exchange, H+-K+ ATPase and Cl-/HCO-3 exchange. In this work
      we studied the functional activity of a vacuolar H+-ATPase in MDCK cells and its
      chloride dependence. We measured intracellular pH (pHi) in monolayers grown on
      glass cover slips utilizing the pH sensitive probe BCECF. To analyze the
      functional activity of the H+ transporters we observed the intracellular
      alkalinization in response to an acute acid load due to a 20 mm NH+4 pulse, and
      calculated the initial rate of pHi recovery (dpHi/dt). The cells have a basal pHi
      of 7.17 +/- 0.01 (n = 23) and control dpHi/dt of 0.121 +/- 0.006 (n = 23) pHi
      units/min. This pHi recovery rate is markedly decreased when Na+ was removed, to
      0.069 +/- 0.004 (n = 16). It was further reduced to 0.042 +/- 0. 005 (n = 12)
      when concanamycin 4.6 x 10(-8) m (a specific inhibitor of the vacuolar H+-ATPase)
      was added to the zero Na+ solution. When using a solution with zero Na+, low K+
      (0.5 mm) plus concanamycin, pHi recovery fell again, significantly, to 0.023 +/-
      0.006 (n = 14) as expected in the presence of a H+-K+-ATPase. This result was
      confirmed by the use of 5 x 10(-5) m Schering 28080. The Na+ independent pHi
      recovery was significantly reduced from 0.069 +/- 0.004 to 0.042 +/- 0.004 (n =
      12) when NPPB 10(-5) m (a specific blocker of Cl- channels in renal tubules) was
      utilized. When the cells were preincubated in 0 Cl-/normal Na+ solution for 8
      min. before the ammonium pulse, the pHi recovery fell from 0.069 +/- 0.004 to
      0.041 +/- 0.007 (n = 12) in a Na+ and Cl- free solution. From these results we
      conclude that: (i) MDCK cells have two Na+-independent mechanisms of pHi
      recovery, a concanamycin sensitive H+-ATPase and a K+ dependent, Schering 28080
      sensitive H+-K+ ATPase; and, (ii) pHi recovery in Na+-free medium depends on the
      presence of a chloride current which can be blocked by NPPB and impaired by
      preincubation in Cl--free medium. This finding supports a role for chloride in
      the function of the H+ ATPase, which might be electrical shunting or a
      biochemical interaction.

PMID- 9592079
TI  - Single-channel characterization of the pharmacological properties of the K(Ca2+)
      channel of intermediate conductance in bovine aortic endothelial cells.
AB  - The pharmacological profile of a voltage-independent Ca2+-activated potassium
      channel of intermediate conductance (IK(Ca2+)) present in bovine aortic
      endothelial cells (BAEC) was investigated in a series of inside-out and outside
      out patch-clamp experiments. Channel inhibition was observed in response to
      external application of ChTX with a half inhibition concentration of 3.3 +/- 0.3
      nm (n = 4). This channel was insensitive to IbTX, but channel block was detected
      following external application of MgTX and StK leading to the rank order toxin
      potency ChTX > StK > MgTX >>IbTX. A reduction of the channel unitary current
      amplitude was also measured in the presence of external TEA, with half reduction
      occurring at 23 +/- 3 mm TEA (n = 3). The effect of TEA was voltage insensitive,
      an indication that TEA may bind to a site located on external side of the pore
      region of this channel. Similarly, the addition of d-TC to the external medium
      caused a reduction of the channel unitary current amplitude with half reduction
      at 4.4 +/- 0.3 mm (n = 4). In contrast, application of d-TC to the bathing medium
      in inside-out experiments led to the appearance of long silent periods, typical
      of a slow blocking process. Finally, the IK(Ca2+) in BAEC was found to be
      inhibited by NS1619, an activator of the Ca2+-activated potassium channel of
      large conductance (Maxi K(Ca2+)), with a half inhibition value of 11 +/- 0.8
      micron (n = 4). These results provide evidence for a pharmacological profile
      distinct from that reported for the Maxi K(Ca2+) channel, with some features
      attributed to the voltage-gated KV1.2 potassium channel.

PMID- 9592080
TI  - Binding of serotonin to receptors at multiple sites is required for structural
      plasticity accompanying long-term facilitation of Aplysia sensorimotor synapses.
AB  - Long-term changes in the efficacy of Aplysia sensorimotor synapses accompany
      nonassociative and associative forms of behavioral plasticity. This synapse
      expresses long-term facilitation either with repeated applications of 5
      hydroxytryptamine (5-HT) or with a single pairing of tetanus in the sensory
      neuron (SN) and bath application of 5-HT. We examined whether structural changes
      in the SN accompany all forms of long-term synaptic enhancement and the locations
      at which 5-HT must bind receptors to evoke long-term functional and/or structural
      changes. Pairing tetanus with one application of 5-HT evoked both functional and
      structural changes after 24 hr only when 5-HT application was temporally paired
      with the tetanus and activated receptors on both the SN cell body and terminal
      region. Repeated application of 5-HT to the terminal region alone failed to evoke
      any long-term change. Repeated applications of 5-HT to the SN cell body alone
      evoked a change in synaptic efficacy at 24 hr but failed to increase SN
      varicosities. Repeated applications of 5-HT to both the SN cell body and the
      terminal region evoked increases in both synaptic efficacy and the number of SN
      varicosities at 24 hr. The results indicate that different external stimuli can
      evoke equivalent forms of long-term synaptic facilitation with or without
      structural changes in the SNs. Changes in the number of SN varicosities can
      accompany different forms of long-term facilitation and require the activation of
      5-HT receptors at multiple sites.

PMID- 9592081
TI  - Pore mutation in a G-protein-gated inwardly rectifying K+ channel subunit causes
      loss of K+-dependent inhibition in weaver hippocampus.
AB  - Weaver (wv) mice carry a point mutation in the pore region of a G-protein-gated
      inwardly rectifying K+ channel subunit (Kir3.2). wvKir3.2 conducts inward
      currents that may cause the loss of neurons in the cerebellum and substantia
      nigra. Although Kir3.2 is widely expressed in the CNS, significant morphological
      or physiological changes have not been reported for other brain areas. We studied
      the role of wvKir3.2 in hippocampal slices of young [postnatal day (P) 4-18] and
      adult wv/wv (>/=P24) mice, because protein levels of Kir 3. 1 and Kir3.2 appear
      to be normal in the first 3 postnatal weeks and only decrease thereafter. In
      disinhibited slices, the GABAB receptor agonist R-baclofen reduced burst activity
      in wv/wv mice but was much more potent in wild-type mice. Mean resting membrane
      potential, slope input resistance, and membrane time constant of CA3 neurons of
      adult wv/wv and wild-type mice were indistinguishable. However, R-baclofen or
      chloroadenosine did not induce K+ currents or any other conductance change in
      wv/wv mice. Moreover, electrical or chemical stimulation of inhibitory neurons
      did not evoke slow IPSPs in adult wv/wv mice. Only in a few cells of young wv/wv
      mice did GABAB receptor activation by R-baclofen or presynaptic stimulation
      induce small inward currents, which were likely caused by a Na+ ion influx
      through wvKir3.2 channels. The data show that the pore mutation in wvKir3.2
      channels results in a hippocampal phenotype resembling Kir3.2-deficient mutants,
      although it is not associated with the occurrence of seizures.

PMID- 9592082
TI  - Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys-Ser-Pro (KSP)
      repeats in neurofilament proteins NF-H and NF-M.
AB  - Mammalian neurofilament proteins, particularly midsized (NF-M) and heavy (NF-H)
      molecular weight neurofilament proteins, are highly phosphorylated in axons.
      Neurofilament function depends on the state of phosphorylation of the numerous
      serine/threonine residues in these proteins. Most phosphorylation occurs in the
      lys-ser-pro (KSP) repeats in the C-terminal tail domains of NF-H and NF-M. In our
      previous study, cyclin-dependent kinase 5 (cdk5) was shown to phosphorylate
      specifically the KSPXK repeats in rat NF-H. Because 80% of the repeats are of the
      KSPXXXK type, it was of interest to determine which kinase phosphorylates these
      motifs. Using a synthetic KSPXXXK peptide to screen for a specific kinase, we
      fractionated rat brain extracts by column chromatography and identified
      extracellular signal-regulated kinase (Erk2) activated by an upstream activator,
      the mitogen-activated protein kinase kinase MAPKK (MEK), by Western blot
      analysis, sequence identification, and inhibition by a specific MEK inhibitor (PD
      98059). The fraction containing Erk2, as well as bacterially expressed Erk1 and
      Erk2, phosphorylated all types of KSP motifs in peptides (KSPXK, KSPXXK, KSPXXXK,
      and KSPXXXXK) derived from NF-M and NF-H. They also phosphorylated an expressed
      24 KSPXXXK repeat NF-H polypeptide, an expressed NF-H as well as dephosphorylated
      native rat NF-H, and NF-M proteins with accompanying decreases in their
      respective electrophoretic mobilities. A comparative kinetic study of Erk2 and
      cdk5 phosphorylation of KSPXK and KSPXXXK peptides revealed that, in contrast to
      cdk5, which phosphorylated only the KSPXK peptide, Erk2 could phosphorylate both.
      The preferred substrate for Erk2 was KSPXXXK peptide. The MEK inhibitor PD 98059
      also inhibited phosphorylation of NF-H, NF-M, and microtubule-associated protein
      (MAP) in primary rat hippocampal cells and caused a decrease in neurite
      outgrowth, suggesting that Erk1,2 may play an important role in neurite growth
      and branching. These data suggest that neuronal Erk1 and Erk2 are capable of
      phosphorylating serine residues in diverse KSP repeat motifs in NF-M and NF-H.

PMID- 9592083
TI  - Modulation of neuronal activity by glial cells in the retina.
AB  - Glial-neuronal communication was studied by monitoring the effect of
      intercellular glial Ca2+ waves on the electrical activity of neighboring neurons
      in the eyecup preparation of the rat. Calcium waves in astrocytes and Muller
      cells were initiated with a mechanical stimulus applied to the retinal surface.
      Changes in the light-evoked spike activity of neurons within the ganglion cell
      layer occurred when, and only when, these Ca2+ waves reached the neurons.
      Inhibition of activity was observed in 25 of 53 neurons (mean decrease in spike
      frequency, 28 +/- 2%). Excitation occurred in another five neurons (mean
      increase, 27 +/- 5%). Larger amplitude Ca2+ waves were associated with greater
      modulation of neuronal activity. Thapsigargin, which reduced the amplitude of the
      glial Ca2+ increases, also reduced the magnitude of neuronal modulation.
      Bicuculline and strychnine, inhibitory neurotransmitter antagonists, as well as 6
      Nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and D(-)-2-amino-7
      phosphonoheptanoic acid (D-AP7), glutamate antagonists, reduced the inhibition of
      neuronal activity associated with glial Ca2+ waves, suggesting that inhibition is
      mediated by inhibitory interneurons stimulated by glutamate release from glial
      cells. The results suggest that glial cells are capable of modulating the
      electrical activity of neurons within the retina and thus, may directly
      participate in information processing in the CNS.

PMID- 9592084
TI  - Endocytotic formation of vesicles and other membranous structures induced by Ca2+
      and axolemmal injury.
AB  - Vesicles and/or other membranous structures that form after axolemmal damage have
      recently been shown to repair (seal) the axolemma of various nerve axons. To
      determine the origin of such membranous structures, (1) we internally dialyzed
      isolated intact squid giant axons (GAs) and showed that elevation of
      intracellular Ca2+ >100 microM produced membranous structures similar to those in
      axons transected in Ca2+-containing physiological saline; (2) we exposed GA
      axoplasm to Ca2+-containing salines and observed that membranous structures did
      not form after removing the axolemma and glial sheath but did form in severed GAs
      after >99% of their axoplasm was removed by internal perfusion; (3) we examined
      transected GAs and crayfish medial giant axons (MGAs) with time-lapse confocal
      fluorescence microscopy and showed that many injury-induced vesicles formed by
      endocytosis of the axolemma; (4) we examined the cut ends of GAs and MGAs with
      electron microscopy and showed that most membranous structures were single-walled
      at short (5-15 min) post-transection times, whereas more were double- and multi
      walled and of probable glial origin after longer (30-150 min) post-transection
      times; and (5) we examined differential interference contrast and confocal images
      and showed that large and small lesions evoked similar injury responses in which
      barriers to dye diffusion formed amid an accumulation of vesicles and other
      membranous structures. These and other data suggest that Ca2+ inflow at large or
      small axolemmal lesions induces various membranous structures (including
      endocytotic vesicles) of glial or axonal origin to form, accumulate, and interact
      with each other, preformed vesicles, and/or the axolemma to repair the axolemmal
      damage.

PMID- 9592085
TI  - Prevention of PC12 cell death by N-acetylcysteine requires activation of the Ras
      pathway.
AB  - We have shown that N-acetylcysteine (NAC) promotes survival of sympathetic
      neurons and pheochromocytoma (PC12) cells in the absence of trophic factors. This
      action of NAC was not related to its antioxidant properties or ability to
      increase intracellular glutathione levels but was instead dependent on ongoing
      transcription and seemed attributable to the action of NAC as a reducing agent.
      Here, we investigate the mechanism by which NAC promotes neuronal survival. We
      show that NAC activates the Ras-extracellular signal-regulated kinase (ERK)
      pathway in PC12 cells. Ras activation by NAC seems necessary for survival in that
      it is unable to sustain serum-deprived PC12 MM17-26 cells constitutively
      expressing a dominant-negative form of Ras. Promotion of PC12 cell survival by
      NAC is totally blocked by PD98059, an inhibitor of the ERK-activating MAP
      kinase/ERK kinase, suggesting a required role for ERK activation in the NAC
      mechanism. In contrast, LY294002 and wortmannin, inhibitors of
      phosphatidylinositol 3-kinase (PI3K) that partially block NGF-promoted PC12 cell
      survival, have no effect on prevention of death by NAC. We hypothesized
      previously that the ability of NAC to promote survival correlates with its
      antiproliferative properties. However, although NAC does not protect PC12 MM17-26
      cells from loss of trophic support, it does inhibit their capacity to synthesize
      DNA. Thus, the antiproliferative effect of NAC does not require Ras activation,
      and inhibition of DNA synthesis is insufficient to mediate NAC-promoted survival.
      These findings highlight the role of Ras-ERK activation in the mechanism by which
      NAC prevents neuronal death after loss of trophic support.

PMID- 9592086
TI  - Neuronal nicotinic acetylcholine receptors are blocked by intracellular spermine
      in a voltage-dependent manner.
AB  - A common feature of neuronal nicotinic acetylcholine receptors (nAChRs) is that
      they conduct inward current at negative membrane potentials but little outward
      current at positive membrane potentials, a property referred to as inward
      rectification. Physiologically, inward rectification serves important functions,
      and the main goal of our study was to investigate the mechanisms underlying the
      rectification of these receptors. We examined recombinant alpha3beta4 and
      alpha4beta2 neuronal nAChR subtypes expressed in Xenopus oocytes and native
      nAChRs expressed on superior cervical ganglion (SCG) neurons. Whole-cell ACh
      evoked currents recorded from these receptors exhibited strong inward
      rectification. In contrast, we showed that single-channel currents from these
      neuronal nAChRs measured in outside-out patches outwardly rectify. On the basis
      of recent findings that spermine, a ubiquitous intracellular polyamine, confers
      rectification to glutamate receptors and inwardly rectifying potassium channels,
      we investigated whether spermine causes neuronal nAChRs to inwardly rectify. When
      spermine was added to the patch electrode in outside-out recordings, it caused a
      concentration- and voltage-dependent block of ACh-evoked single-channel currents.
      Using these single-channel data and physiological concentrations of intracellular
      spermine, we could account for the inward rectification of macroscopic whole-cell
      ACh-evoked conductance-voltage relationships. Therefore, we conclude that the
      voltage-dependent block by intracellular spermine underlies inward rectification
      of neuronal nAChRs. We also found that extracellular spermine blocks both
      alpha3beta4 and alpha4beta2 receptors; this finding points to a mechanism whereby
      increases in extracellular spermine, perhaps during pathological conditions,
      could selectively block these receptors.

PMID- 9592087
TI  - Connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease show
      two distinct behaviors: loss of function and altered gating properties.
AB  - The X-linked form of Charcot-Marie-Tooth disease (CMTX) is associated with
      mutations in the gene encoding connexin32 (Cx32), which is expressed in Schwann
      cells. We have compared the functional properties of 11 Cx32 mutations with those
      of the wild-type protein by testing their ability to form intercellular channels
      in the paired oocyte expression system. Although seven mutations were
      functionally incompetent, four others were able to generate intercellular
      currents of the same order of magnitude as those induced by wild-type Cx32
      (Cx32wt). In homotypic oocyte pairs, CMTX mutations retaining functional activity
      induced the development of junctional currents that exhibited changes in the
      sensitivity and kinetics of voltage dependence with respect to that of Cx32wt.
      The four mutations were also capable of interacting in heterotypic configuration
      with the wild-type protein, and in one case the result was a marked rectification
      of junctional currents in response to voltage steps of opposite polarity. In
      addition, the functional CMTX mutations displayed the same selective pattern of
      compatibility as Cx32wt, interacting with Cx26, Cx46, and Cx50 but failing to do
      so with Cx40. Although the functional mutations exhibited sensitivity to
      cytoplasmic acidification, which induced a >/=80% decrease in junctional
      currents, both the rate and extent of channel closure were enhanced markedly for
      two of them. Together, these results indicate that the functional consequences of
      CMTX mutations of Cx32 are of two drastically distinct kinds. The presence of a
      functional group of mutations suggests that a selective deficit of Cx32 channels
      may be sufficient to impair the homeostasis of Schwann cells and lead to the
      development of CMTX.

PMID- 9592088
TI  - Non-cell-autonomous photoreceptor degeneration in rds mutant mice mosaic for
      expression of a rescue transgene.
AB  - The inherited retinal dystrophies represent a large and heterogenous group of
      hereditary neurodegenerations, for many of which, the molecular defect has been
      defined. However, the mechanism of cell death has not been determined for any
      form of retinal degeneration. The retinal degeneration slow (rds-/-) mutation of
      mice is associated with nondevelopment of photoreceptor outer segments and
      gradual death of photoreceptor cell bodies, attributed to the absence of the
      outer segment protein rds/peripherin. Here, we examined the effects of a
      transgene encoding normal rds/peripherin that had integrated into the X
      chromosome in male and female rds-/- mutant retinas. In 2-month-old transgenic
      males and homozygous-transgenic females on rds-/-, we observed virtually complete
      rescue of both the outer segment nondevelopment and photoreceptor degeneration.
      In contrast, hemizygous-transgenic rds-/- female littermates showed patchy
      distributions of the transgene mRNA, by in situ hybridization analysis, and of
      photoreceptor cells that contain outer segments. This pattern is consistent with
      random inactivation of the X-chromosome and mosaic expression of the transgene.
      Surprisingly, we observed significant photoreceptor cell loss in both transgene
      expressing and nonexpressing patches in hemizygous female retinas. These
      observations were supported by nuclease protection analysis, which showed notably
      lower than predicted levels of transgene mRNA in retinas from hemizygous females
      compared with male and homozygous female littermates. This phenotype suggests an
      important component of non-cell-autonomous photoreceptor death in rds-/- mutant
      mice. These results have significance to both the etiology and potential
      treatment of human inherited retinal degenerations.

PMID- 9592089
TI  - Purification of a multipotent antideath activity from bovine liver and its
      identification as arginase: nitric oxide-independent inhibition of neuronal
      apoptosis.
AB  - Catalase is an antioxidant enzyme that has been shown to inhibit apoptotic or
      necrotic neuronal death induced by hydrogen peroxide. We report the purification
      of a contaminating antiapoptotic activity from a commercial bovine liver catalase
      preparation by following its ability to inhibit apoptosis when applied
      extracellularly in multiple death paradigms. The antiapoptotic activity was
      identified by protein microsequencing as arginase, a urea cycle and nitric oxide
      synthase-regulating enzyme, and confirmed by demonstrating the presence of
      antiapoptotic activity in a >97% pure preparation of recombinant arginase. The
      pluripotency of recombinant arginase was demonstrated by its ability to inhibit
      apoptosis in multiple paradigms including rat cortical neurons induced to die by
      glutathione depletion and oxidative stress, by 100 nM staurosporine treatment, or
      by Sindbis virus infection. The protective effects of arginase in these apoptotic
      paradigms, in contrast to previous studies on excitotoxic neuronal necrosis, are
      independent of nitric oxide synthase inhibition. Rather, arginase-induced
      depletion of arginine leads to inhibition of protein synthesis, resulting in cell
      survival. Because inhibitors of nitric oxide synthesis and of protein synthesis
      have been shown to decrease necrotic and apoptotic death, respectively, in animal
      models of stroke and spinal cord injury, arginine-depleting enzymes, capable of
      simultaneously inhibiting protein synthesis and nitric oxide generation, may be
      propitious therapeutic agents for acute neurological diseases. Furthermore, our
      results suggest caution in attributing the cytoprotective effects of some
      catalase preparations to catalase.

PMID- 9592090
TI  - Kir2.4: a novel K+ inward rectifier channel associated with motoneurons of
      cranial nerve nuclei.
AB  - Members of the Kir2 subfamily of inwardly rectifying K+ channels characterized by
      their strong current rectification are widely expressed both in the periphery and
      in the CNS in mammals. We have cloned from rat brain a fourth subfamily member,
      designated Kir2.4 (IRK4), which shares 53-63% similarity to Kir2.1, Kir2.2, or
      Kir2.3 on the amino acid level. In situ hybridization analysis identifies Kir2.4
      as the most restricted of all Kir subunits in the brain. Kir2. 4 transcripts are
      expressed predominantly in motoneurons of cranial nerve motor nuclei within the
      general somatic and special visceral motor cell column and thus are uniquely
      related to a functional system. Heterologous expression of Kir2.4 in Xenopus
      oocytes and mammalian cells gives rise to low-conductance channels (15 pS), with
      an affinity to the channel blockers Ba2+ (Ki = 390 microM) and Cs+ (Ki = 8.06 mM)
      30-50-fold lower than in other Kir channels. Low Ba2+ sensitivity allows
      dissection of Kir2.4 currents from other Kir conductances in hypoglossal
      motoneurons (HMs) in rat brainstem slices. The finding that Ba2+-mediated block
      of Kir2.4 in HMs evokes tonic activity and increases the frequency of induced
      spike discharge indicates that Kir2.4 channels are of major importance in
      controlling excitability of motoneurons in situ.

PMID- 9592091
TI  - Presynaptic recording of quanta from midbrain dopamine neurons and modulation of
      the quantal size.
AB  - The observation of quantal release from central catecholamine neurons has proven
      elusive because of the absence of evoked rapid postsynaptic currents. We adapted
      amperometric methods to observe quantal release directly from axonal varicosities
      of midbrain dopamine neurons that predominantly contain small synaptic vesicles.
      Quantal events were elicited by high K+ or alpha-latrotoxin, required
      extracellular Ca2+, and were abolished by reserpine. The events indicated the
      release of 3000 molecules over 200 microsec, much smaller and faster events than
      quanta associated with large dense-core vesicles previously recorded in
      vertebrate preparations. The number of dopamine molecules per quantum increased
      as a population to 380% of controls after glial-derived neurotrophic factor
      (GDNF) exposure and to 350% of controls after exposure to the dopamine precursor
      L-dihydroxyphenylalanine (L-DOPA). These results introduce a means to measure
      directly the number of transmitter molecules released from small synaptic
      vesicles of CNS neurons. Moreover, quantal size was not an invariant parameter in
      CNS neurons but could be modulated by neurotrophic factors and altered
      neurotransmitter synthesis.

PMID- 9592092
TI  - Modulation of rat rotational behavior by direct gene transfer of constitutively
      active protein kinase C into nigrostriatal neurons.
AB  - The modulation of motor behavior by protein kinase C (PKC) signaling pathways in
      nigrostriatal neurons was examined by using a genetic intervention approach.
      Herpes simplex virus type 1 (HSV-1) vectors that encode a catalytic domain of rat
      PKCbetaII (PkcDelta) were developed. PkcDelta exhibited a constitutively active
      protein kinase activity with a substrate specificity similar to that of rat brain
      PKC. As demonstrated in cultured sympathetic neurons, PkcDelta caused a long
      lasting, activation-dependent increase in neurotransmitter release. In the rat
      brain, microinjection of HSV-1 vectors that contain the tyrosine hydroxylase
      promoter targeted expression to dopaminergic nigrostriatal neurons. Expression of
      pkcDelta in a small percentage of nigrostriatal neurons (approximately 0.1-2%)
      was sufficient to produce a long-term (>/=1 month) change in apomorphine-induced
      rotational behavior. Nigrostriatal neurons were the only catecholaminergic
      neurons that contained PkcDelta, and the amount of rotational behavior was
      correlated with the number of affected nigrostriatal neurons. The change in
      apomorphine-induced rotational behavior was blocked by a dopamine receptor
      antagonist (fluphenazine). D2-like dopamine receptor density was increased in
      those regions of the striatum innervated by the affected nigrostriatal neurons.
      Therefore, this strategy enabled the demonstration that a PKC pathway or PKC
      pathways in nigrostriatal neurons modulate apomorphine-induced rotational
      behavior, and altered dopaminergic transmission from nigrostriatal neurons
      appears to be the affected neuronal physiology responsible for the change in
      rotational behavior.

PMID- 9592093
TI  - Regulation of the nigrostriatal pathway by metabotropic glutamate receptors
      during development.
AB  - Dopamine neurons in the substantia nigra heavily innervate the striatum, making
      it the nucleus with the highest levels of dopamine in the adult brain. The
      present study analyzes the time course and the density of striatal innervation by
      nigral dopamine neurons and characterizes the role of the neurotransmitter
      glutamate during the development of the nigrostriatal pathway. For this purpose,
      organotypic cultures containing the cortex, the striatum, and the substantia
      nigra (triple cultures) were prepared from rat brains at postnatal day (PND) 0-2
      and were cultured for up to 60 d in vitro (DIV). Dopamine fibers and neurons were
      labeled using tyrosine hydroxylase (TH) immunohistochemistry. Striatal TH-ir
      fiber density was quantitatively analyzed using confocal laser scanning
      microscopy (CLSM). In long-term triple cultures (44 +/- 3 DIV), the striatal
      dopamine fiber density was high and was weakly correlated with the number of
      nigral dopamine neurons. The high striatal dopamine fiber density mainly resulted
      from an enhanced ingrowth and ramification of dopamine fibers from nigral neurons
      during 8-17 DIV. The metabotropic glutamate receptor (mGluR) antagonist L(+)-2
      amino-3-phosphonopropionic acid (L-AP-3) selectively inhibited this dopaminergic
      innervation of the striatum, whereas ionotropic GluR antagonists had no effect.
      The L-AP-3-mediated inhibition was prevented by the mGluR agonist 1S, 3R
      aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). The inhibition of the
      striatal dopaminergic innervation by L-AP-3 was further confirmed by anterograde
      tracing of the nigrostriatal projection with Phaseolus vulgaris leucoagglutinin.
      These results indicate that glutamate, by acting on group I mGluRs, plays an
      important "trophic" role for the development of the nigrostriatal dopamine
      pathway.

PMID- 9592094
TI  - The development of local, layer-specific visual cortical axons in the absence of
      extrinsic influences and intrinsic activity.
AB  - The laminar specificity of vertical connections in the primary visual cortex
      (area 17) develops precisely from the outset, leading to the hypothesis that
      layer-specific axonal targeting is attributable to molecular cues intrinsic to
      the cortex (Lund et al., 1977; Katz and Callaway, 1992). However, alternative
      factors that could influence axonal development have not been investigated. This
      study examines the roles of intrinsic cortical activity and extrinsic influences
      that could arise from earlier-formed connections with outside cortical and
      subcortical areas. Organotypic slice cultures were prepared from ferret area 17
      before the formation of local axonal connections and were incubated for 5-7 d to
      allow initial, local axonal arbors to form in the absence of extrinsic
      influences. Additionally, some slices were cultured in the presence of the Na+
      channel blocker tetrodotoxin to block spontaneous action potentials within the
      slice. Individual neurons were labeled intracellularly with biocytin, and their
      patterns of local axonal arborizations were reconstructed. This study focuses on
      the development of layer 6 pyramidal neurons, the axons of which in vivo bypass
      an incorrect target, layer 5, before specifically arborizing in their local
      target, layer 4. We found that axonal arbors developing in vitro preferentially
      arborized in layer 4 versus layer 5. However, inhibition of spontaneous activity
      within the cortical slice decreased this specificity, resulting in similar
      numbers of axonal branches in layers 4 and 5. Thus, although cortical axons do
      not require influences from outside areas, intrinsic spontaneous activity is
      required for specific axonal arborization in correct laminar targets.

PMID- 9592095
TI  - Direct participation of starburst amacrine cells in spontaneous rhythmic
      activities in the developing mammalian retina.
AB  - Spontaneous, rhythmic waves of excitation in the developing mammalian retina play
      a critical role in the formation of precise neuronal connectivity in the visual
      system. However, it is not known what circuits in the retina are responsible for
      the production of these waves. Using patch-clamp recordings in the whole-mount
      neonatal rabbit retina, this study reports that the displaced starburst amacrine
      cell, a unique cholinergic interneuron in the ganglion cell layer of the retina,
      undergoes rhythmic bursts of membrane depolarization with a frequency and
      duration similar to those of spontaneous retinal waves. Simultaneous patch-clamp
      recordings from pairs of neighboring starburst and ganglion cells show that the
      rhythmic activity in starburst cells is closely correlated with that in ganglion
      cells, and that the excitation in both cell types is most likely driven by
      synaptic input. However, in contrast to ganglion cells, displaced starburst cells
      usually do not generate spontaneous somatic action potentials. Instead, they seem
      to use subthreshold potentials (at least at the soma) to mediate the rhythmic
      excitation. The results suggest that acetylcholine is likely released
      rhythmically in the developing retina. Thus, starburst amacrine cells form the
      first identified network of retinal interneurons that directly participate in
      spontaneous rhythmic activities in the developing retina.

PMID- 9592096
TI  - Rapsyn clusters neuronal acetylcholine receptors but is inessential for formation
      of an interneuronal cholinergic synapse.
AB  - Nicotinic acetylcholine receptors (AChRs) are clustered at high density in the
      postsynaptic membranes of skeletal neuromuscular junctions and cholinergic
      interneuronal synapses. A cytoplasmic protein, rapsyn, is essential for AChR
      clustering in muscle. Here, we asked whether rapsyn mediates neuronal AChR
      clustering at cholinergic synapses in a mammalian sympathetic ganglion, the
      superior cervical ganglion (SCG). Several observations supported this
      possibility: (1) AChR clusters containing the alpha3-5 and beta2 subunits,
      homologs of the muscle AChR subunits, are present at SCG synapses; (2) rapsyn RNA
      is readily detectable in the SCG; and (3) expression of recombinant rapsyn in
      heterologous cells induces aggregation of coexpressed neuronal AChR subunits.
      However, rapsyn protein was undetectable at ganglionic synaptic sites. Moreover,
      aggregates of neuronal AChRs induced in heterologous cells by full-length rapsyn
      remained intracellular, whereas rapsyn-induced clusters of muscle AChRs reached
      the cell surface. Additional studies revealed a second rapsyn RNA species in SCG
      generated by alternative splicing and competent to encode a novel short rapsyn
      isoform. However, this isoform clustered neither neuronal nor muscle AChRs in
      heterologous cells. Most telling, the number, size, and density of AChR clusters
      in SCG did not differ significantly between neonatal mice bearing a targeted
      mutation of the rapsyn gene and littermate controls. Thus, rapsyn is dispensable
      for clustering of ganglionic neuronal nicotinic AChRs.

PMID- 9592097
TI  - Hippocampal synaptic plasticity in mice overexpressing an embryonic subunit of
      the NMDA receptor.
AB  - The effects of changing NMDA receptor subunit composition on synaptic plasticity
      in the hippocampus were analyzed by creating transgenic mice overexpressing NR2D,
      a predominantly embryonic NMDA receptor subunit. NMDA-evoked currents in the
      transgenic mice had smaller amplitudes and slower kinetics. The transgenics also
      displayed age-dependent deficits in synaptic plasticity in area CA1 of the
      hippocampus. Long-term depression was selectively impaired in juvenile mice when
      NR2D overexpression was moderate. In mature mice, overexpression of NR2D was
      associated with a reduction of both NR2B and Ca2+-independent activity of Ca2+-
      and calmodulin-dependent protein kinase II. These biochemical changes were
      correlated with a marked impairment of NMDA-dependent long-term potentiation, but
      spatial behavior was normal in these mice. These results show that the
      developmental regulation of NMDA receptor subunit composition alters the
      frequency at which modification of synaptic responses occur after afferent
      stimulation.

PMID- 9592098
TI  - G protein-mediated inhibition of neuronal migration requires calcium influx.
AB  - Neuronal migration is an essential feature of the developing nervous system, but
      the intracellular signaling mechanisms that regulate this process are poorly
      understood. During the formation of the enteric nervous system (ENS) in the moth
      Manduca sexta, the migration of an identified set of neurons (the EP cells) is
      regulated in part by the heterotrimeric guanyl-nucleotide binding protein (G
      protein) Goalpha. Using an in vivo culture preparation for developing embryos
      that allows direct access to the ENS, we have shown that EP cell migration is
      similarly regulated by intracellular Ca2+; treatments that increased
      intracellular Ca2+ inhibited the migratory process, whereas buffering
      intracellular Ca2+ induced aberrant migration onto inappropriate pathways.
      Imaging the spontaneous changes in intracellular Ca2+ within individual EP cells
      showed that actively migrating neurons exhibited only small fluctuations in
      intracellular Ca2+. In contrast, neurons that had reached the end of migration
      displayed large, transient Ca2+ spikes. Similar Ca2+ spikes were induced in the
      EP cells by G protein stimulation, an effect that was reversed by removal of
      external Ca2+. Stimulation of Go in individual EP cells (by injection of either
      activated Goalpha subunits or mastoparan) also inhibited migration in a Ca2+
      dependent manner. These results suggest that the regulation of neuronal migration
      by G proteins involves a Ca2+-dependent process requiring Ca2+ influx.

PMID- 9592099
TI  - Distinctive morphological features of a subset of cortical neurons grown in the
      presence of basal forebrain neurons in vitro.
AB  - Basal forebrain cholinergic neurons (BFCNs) provide the major subcortical source
      of cholinergic input to cerebral cortex and play an important role in regulating
      cortical activity. The present study examined the ability of BFCNs to influence
      neocortical neuronal growth by examining effects of the presence of BFCNs on
      certain cortical neurons grown under the controlled conditions of dissociated
      cell culture. Initial experiments demonstrated distinctive morphological features
      of a population of neurons (labeled with SMI-32, a monoclonal antibody to
      nonphosphorylated neurofilament proteins that labels pyramidal neurons in vivo)
      in cocultures containing basal forebrain (BF) and cortical cells. These neurons
      (large neurons immunoreactive for SMI-32 [SMI-32(+) neurons]) were characterized
      as having extensive axons, greater soma size, and more dendritic growth than did
      most SMI-32(+) neurons in the cultures. Staining for SMI-32 in cocultures in
      which the cortical neurons were labeled with a fluorescent marker before adding
      the BF cells indicated that virtually all large SMI-32(+) neurons were of
      cortical origin. Eliminating BFCNs with the selective cholinergic immunotoxin 192
      IgG-saporin resulted in a >80% decrease in the number of large SMI-32(+) neurons,
      although causing little damage to other cells in the treated cultures; this
      suggests that survival or maintenance of large SMI-32(+) neurons may depend on
      ongoing trophic support from BFCNs. Thus, present findings suggest that BFCNs may
      provide powerful growth- and/or survival-enhancing signals to a subset of
      cortical neurons.

PMID- 9592100
TI  - Extensive divergence and convergence in the thalamocortical projection to monkey
      somatosensory cortex.
AB  - This study examined the extent of thalamocortical divergence as a potential
      determinant of activity-dependent representational plasticity in area 3b of adult
      monkey somatosensory cortex. Single or paired injections of anterogradely
      transported tracers, of varying anteroposterior extent, were made horizontally
      from behind in defined parts of the body representation in the ventral posterior
      lateral (VPL) and/or ventral posterior medial (VPM) thalamic nuclei, and the
      distribution and density of labeled thalamocortical terminations were mapped in
      cortex. Injections of increasing size in any dimension of VPL or VPM resulted in
      increasing accumulation of labeled terminals within the region of projection,
      implying extensive convergence of individual axons. Anteroposteriorly elongated
      injections labeled mediolaterally extended but anteroposteriorly restricted zones
      in cortex. Dorsoventral placement of an injection in VPL or VPM determined
      anteroposterior location of labeling in cortex. Dual injections separated
      mediolaterally or dorsoventrally by approximately 1 mm, and in different parts of
      the thalamic body or head-face representation gave rise to labeled
      thalamocortical terminations that overlapped extensively. For injection sites at
      different anteroposterior levels in VPL or VPM, the area of cortical convergence
      was related to their extent of anteroposterior coincidence. Labeled terminations
      arising from injections in immediately adjacent parts of VPL and VPM did not
      overlap in cortex. The extent of thalamocortical divergence and convergence
      revealed by these experiments is greater than that predictable from labeling of
      single axons and is sufficiently great to account for representational plasticity
      that exceeds the 1.5 mm cortical "distance limit."

PMID- 9592101
TI  - Pinna movements of the cat during sound localization.
AB  - We measured the movements of the external ear, or pinna, using the magnetic
      search coil technique in cats trained to look at auditory and visual targets for
      a food reward. No behavioral contingencies were placed on pinna movements.
      Prominent pinna movements accompany eye movements when the animal orients to
      either auditory or visual stimuli. In visual trials the pinna movements are
      coordinated with eye movements, suggesting that they are part of the general
      orientation response of the animal. In auditory trials the pinna response was
      composed of two movements: short- and long-latency components. Whereas the long
      latency component seemed to occur with the eye movement to the target, the short
      latency component was coupled to the onset of the stimulus. The short-latency
      component ( approximately 25 msec) was highly asymmetrical, being largest in the
      pinna ipsilateral to the stimuli. In one animal it persisted after >10(5) trials.

PMID- 9592102
TI  - Induced gamma-band activity during the delay of a visual short-term memory task
      in humans.
AB  - It has been hypothesized that visual objects could be represented in the brain by
      a distributed cell assembly synchronized on an oscillatory mode in the gamma-band
      (20-80 Hz). If this hypothesis is correct, then oscillatory gamma-band activity
      should appear in any task requiring the activation of an object representation,
      and in particular when an object representation is held active in short-term
      memory: sustained gamma-band activity is thus expected during the delay of a
      delayed-matching-to-sample task. EEG was recorded while subjects performed such a
      task. Induced (e.g., appearing with a jitter in latency from one trial to the
      next) gamma-band activity was observed during the delay. In a control task, in
      which no memorization was required, this activity disappeared. Furthermore, this
      gamma-band activity during the rehearsal of the first stimulus representation in
      short-term memory peaked at both occipitotemporal and frontal electrodes. This
      topography fits with the idea of a synchronized cortical network centered on
      prefrontal and ventral visual areas. Activities in the alpha band, in the 15-20
      Hz band, and in the averaged evoked potential were also analyzed. The gamma-band
      activity during the delay can be distinguished from all of these other components
      of the response, on the basis of either its variations or its topography. It thus
      seems to be a specific functional component of the response that could correspond
      to the rehearsal of an object representation in short-term memory.

PMID- 9592103
TI  - Differentially interconnected networks of GABAergic interneurons in the visual
      cortex of the cat.
AB  - Networks of GABAergic neurons have been implicated in neuronal population
      synchronization. To define the extent of cellular interconnections, we determined
      the effect, number, and subcellular distribution of synapses between putative
      GABAergic neurons in layers II-IV of the cat visual cortex using paired
      intracellular recordings in vitro followed by correlated light and electron
      microscopy. All neurons having interneuronal electrophysiological properties were
      classified by their postsynaptic target profile and were identified as basket
      (BC; n = 6), dendrite-targeting (DTC; n = 1), and double bouquet (DBC; n = 2)
      cells. In four out of five anatomically fully recovered and reconstructed cell
      pairs, synaptic connections were found to be reciprocal. Generally BCs
      established synaptic junctions closer (21 +/- 20 micron) to postsynaptic somata
      than did DBCs (43 +/- 19 micron; p < 0.01). The unitary number of synapses (n
      values, 10, 7, and 20) in each of three BC-to-BC pairs was higher than that in
      three BC-to-DBC (n values, 1, 2, and 2) and three DBC-to-BC (n values, 1, 4, and
      4) connections (p < 0.05). A BC innervated a DTC through two synaptic junctions.
      Unitary postsynaptic effects mediated by five BCs could be recorded in two BCs,
      two DBCs, and a DTC. The BCs elicited short-duration fast IPSPs, similar to those
      mediated by GABAA receptors. At a membrane potential of -55.0 +/- 6.4 mV, unitary
      IPSPs (n = 5) had a mean amplitude of 919 +/- 863 microV. Postsynaptic response
      failures were absent when an IPSP was mediated by several release sites. Thus,
      distinct GABAergic interneurons form reciprocally interconnected networks. The
      strength of innervation and the proximal placement of synapses suggest a
      prominent role for BCs in governing the activity of intracortical GABAergic
      networks in layers II-IV.

PMID- 9592104
TI  - Characterization of intrastriatal recombinant adeno-associated virus-mediated
      gene transfer of human tyrosine hydroxylase and human GTP-cyclohydrolase I in a
      rat model of Parkinson's disease.
AB  - To achieve local, continuous L-DOPA delivery in the striatum by gene replacement
      as a model for a gene therapy for Parkinson's disease, the present studies used
      high titer purified recombinant adeno-associated virus (rAAV) containing cDNAs
      encoding human tyrosine hydroxylase (hTH) or human GTP-cyclohydrolase I [GTPCHI,
      the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis] or both to
      infect the 6-OHDA denervated rat striatum. Striatal TH and GTPCHI staining was
      observed 3 weeks after rAAV transduction, with little detectable perturbation of
      the tissue. Six months after intrastriatal rAAV transduction, TH staining was
      present but apparently reduced compared with the 3 week survival time. In a
      separate group of animals, striatal TH staining was demonstrated 1 year after
      rAAV transduction. Double staining studies using the neuronal marker NeuN
      indicated that >90% of rAAV-transduced cells expressing hTH were neurons.
      Microdialysis experiments indicated that only those lesioned animals that
      received the mixture of MD-TH and MD-GTPCHI vector displayed BH4 independent in
      vivo L-DOPA production (mean approximately 4-7 ng/ml). Rats that received the hTH
      rAAV vector alone produced measurable L-DOPA (mean approximately 1-4 ng/ml) only
      after receiving exogenous BH4. L-Aromatic amino acid decarboxylase blockade, but
      not 100 mM KCl-induced depolarization, enhanced L-DOPA overflow, and animals in
      the non-hTH groups (GTPCHI and alkaline phosphatase) yielded minimal L-DOPA.
      Although elevated L-DOPA was observed in animals that received mixed hTH and
      hGTPCHI rAAV vectors, there was no reduction of apomorphine-induced rotational
      behavior 3 weeks after intrastriatal vector injection. These data demonstrate
      that purified rAAV, a safe and nonpathogenic viral vector, mediates long-term
      striatal hTH transgene expression in neurons and can be used to successfully
      deliver L-DOPA to the striatum.

PMID- 9592106
TI  - Identification, localization, and modulation of neural networks for walking in
      the mudpuppy (Necturus maculatus) spinal cord.
AB  - We tested the hypothesis that the neural networks for walking in the mudpuppy can
      be divided into a flexor and an extensor center, each of which contains
      collections of interneurons localized in the vicinity of their motoneuron pools.
      Combining a battery of techniques, we identified and localized the elbow flexor
      center and its motoneuron pool in the C2 segment and the elbow extensor center
      and its motoneuron pool in the C3 segment. Rhythmic flexion or extension of the
      limb in isolation could be induced by continuous trains of current pulses of the
      C2 or C3 segments, respectively. Independent activation could also occur after
      application of glutamate receptor agonist NMDA. Part of segment C2 in isolation
      generated rhythmic elbow flexor bursts, whereas part of segment C3 in isolation
      generated rhythmic elbow extensor bursts. An isolated region spanning the C3
      roots generated both flexor and extensor bursts. The step cycle was modulated in
      a phase-dependent manner by stimulation of the dorsal roots, the ventral roots,
      or either of the two centers. The effects of ventral root stimulation were
      removed by deafferentation to block reafferent input attributable to muscle
      contraction induced by the stimulation. We conclude that the neural networks for
      walking contain at least a flexor and an extensor generator that are localized in
      close apposition to the motoneuron pools, that the two centers can work
      independently despite the fact that there are reciprocal inhibitory
      interconnections between them, and that sensory input interacts with the spinal
      neural networks to reset the ongoing walking rhythm in a phase-dependent manner.

PMID- 9592107
TI  - Expression of integrin-associated protein gene associated with memory formation
      in rats.
AB  - The present study has adopted the PCR differential display method to identify
      cDNA clones associated with memory formation in rats. The one-way inhibitory
      avoidance learning task was used as the behavioral paradigm. Total RNA isolated
      from the hippocampus of poor-memory (<80 sec) and good-memory (600 sec) rats 3 hr
      after training was used for comparison. Three cDNA fragments corresponding to
      different spliced forms of integrin-associated protein (IAP) mRNA were found to
      be differentially expressed in the hippocampus of good-memory rats. Quantitative
      reverse transcription-PCR revealed approximately four fold higher of IAP mRNA
      level in good-memory rats. This result was confirmed further by in situ
      hybridization analysis, and the major difference was in the dentate gyrus. It has
      been demonstrated that this difference in IAP mRNA expression is not attributable
      to different sensitivities of individual rats to electric shock. Rapid
      amplification of cDNA ends obtained the full-length IAP cDNA, which is 1192 bp in
      length excluding the poly(A+) tail. The IAP mRNA expression was significantly
      upregulated by NMDA and amphetamine injections to the dentate gyrus of the
      hippocampus. On the other hand, injection of antisense oligonucleotide
      complementary to the IAP transcript markedly impaired memory retention in rats
      and decreased the amplitude and slope of EPSP in the in vivo long-term
      potentiation paradigm. These results together suggest that IAP gene expression
      plays an important role in memory formation and synaptic plasticity in rat
      hippocampus.

PMID- 9592105
TI  - Seizure-induced neuronal injury: vulnerability to febrile seizures in an immature
      rat model.
AB  - Febrile seizures are the most common seizure type in young children. Whether they
      induce death of hippocampal and amygdala neurons and consequent limbic (temporal
      lobe) epilepsy has remained controversial, with conflicting data from prospective
      and retrospective studies. Using an appropriate-age rat model of febrile
      seizures, we investigated the acute and chronic effects of hyperthermic seizures
      on neuronal integrity and survival in the hippocampus and amygdala via molecular
      and neuroanatomical methods. Hyperthermic seizures-but not hyperthermia alone
      resulted in numerous argyrophilic neurons in discrete regions of the limbic
      system; within 24 hr of seizures, a significant proportion of neurons in the
      central nucleus of the amygdala and in the hippocampal CA3 and CA1 pyramidal cell
      layer were affected. These physicochemical alterations of hippocampal and
      amygdala neurons persisted for at least 2 weeks but were not accompanied by
      significant DNA fragmentation, as determined by in situ end labeling. By 4 weeks
      after the seizures, no significant neuronal dropout in these regions was evident.
      In conclusion, in the immature rat model, hyperthermic seizures lead to profound,
      yet primarily transient alterations in neuronal structure.

PMID- 9592108
TI  - The papilla neglecta of turtles: a detector of head rotations with unique sensory
      coding properties.
AB  - The turtle papilla neglecta (PN) is a small organ lying in the ventrolateral
      utricular wall between the posterior crista (PC) and the utriculosaccular
      foramen. Innervated by a branch of the posterior ampullary nerve, the organ is
      covered by a cupula extending only a small distance into the endolymphatic space.
      Although most rotation-sensitive units in the posterior division of the eighth
      nerve have sensory coding properties expected of PC fibers, a few have unique
      properties. Intra-axonal labeling studies show that the former are PC units and
      the latter are PN units. PC units are maximally responsive to head rotations in
      the posterior canal plane and are sensitive to a combination of angular velocity
      and angular acceleration. PN units respond maximally to pitch rotations and are
      sensitive to a combination of angular acceleration and angular jerk. A maximal
      response to pitches can be related to the location of the PN, which allows it to
      sample endolymph flow from both vertical semicircular canals. Differences in
      response dynamics may reflect macromechanics. Because the cupula of each vertical
      canal occludes the endolymphatic space, its displacement should be proportional
      to endolymph displacement. In contrast, the PN cupula is probably coupled to
      endolymph flow by viscous forces, in which case its displacement should be
      proportional to endolymph velocity. In many vertebrates, the PN is similar to
      that seen in turtles in its location and in the size and shape of its cupula,
      which suggests that its function in these other species is also similar.

PMID- 9592109
TI  - Translation-invariant orientation tuning in visual "complex" cells could derive
      from intradendritic computations.
AB  - first distinguished "simple" from "complex" cells in visual cortex and proposed a
      processing hierarchy in which rows of LGN cells are pooled to drive oriented
      simple cell subunits, which are pooled in turn to drive complex cells. Although
      parsimonious and highly influential, the pure hierarchical model has since been
      challenged by results indicating that many complex cells receive excitatory
      monosynaptic input from LGN cells or do not depend on simple cell input.
      Alternative accounts of complex cell orientation tuning remain scant, however,
      and the function of monosynaptic LGN contacts onto complex cell dendrites remains
      unknown. We have used a biophysically detailed compartmental model to investigate
      whether nonlinear integration of LGN synaptic inputs within the dendrites of
      individual pyramidal cells could contribute to complex-cell receptive field
      structure. We show that an isolated cortical neuron with "active" dendrites,
      driven only by excitatory inputs from overlapping ON- and OFF-center LGN
      subfields, can produce clear phase-invariant orientation tuning-a hallmark
      response characteristic of a complex cell. The tuning is shown to depend
      critically both on the spatial arrangement of LGN synaptic contacts across the
      complex cell dendritic tree, established by a Hebbian developmental principle,
      and on the physiological efficacy of excitatory voltage-dependent dendritic ion
      channels. We conclude that unoriented LGN inputs to a complex cell could
      contribute in a significant way to its orientation tuning, acting in concert with
      oriented inputs to the same cell provided by simple cells or other complex cells.
      As such, our model provides a novel, experimentally testable hypothesis regarding
      the basis of orientation tuning in the complex cell population, and more
      generally underscores the potential importance of nonlinear intradendritic
      subunit processing in cortical neurophysiology.

PMID- 9592110
TI  - Voila, a new Drosophila courtship variant that affects the nervous system:
      behavioral, neural, and genetic characterization.
AB  - In Drosophila melanogaster, a specific PGAL4 transposon induces the Voila1
      genetic variant and produces multiple phenotypes. Homozygous Voila1/1 flies
      rarely reach adulthood, whereas heterozygous Voila1/+ adult males show strong
      bisexual behavior. Males with a single copy of Voila1 driving the feminizing
      transgene UAS-transformer show very reduced sexual activity but no overall effect
      on their behavior. Voila1 is specifically expressed in the nervous system. In the
      CNS, it is expressed mainly in the mushroom bodies and, to a lesser extent, in
      the antennal lobes. In the peripheral nervous system, GAL4 expression is almost
      entirely restricted to the gustatory sensilla. Using chromosomal deficiencies,
      the behavioral alteration was genetically mapped to the same location as the
      PGAL4 element (86E1-2). The multiple behavioral effects of the Voila genetic
      variant are discussed in light of its expression in the nervous system and its
      genetic basis.

PMID- 9592111
TI  - Divergence in the expression of molecular markers of neuronal activation in the
      parvocellular paraventricular nucleus of the hypothalamus evoked by alcohol
      administration via different routes.
AB  - Immediate early gene (IEG) expression has been routinely used by neuroscientists
      as an index of neuronal activation. In the case of the hypothalamic-pituitary
      adrenal axis, induction of c-fos and/or NGFI-B mRNAs in the parvocellular
      paraventricular nucleus (pPVN) has been documented after a variety of stimuli
      that increase adrenocorticotropin (ACTH) in the systemic circulation. However,
      the functional relationship between expression of IEGs and transcription of the
      genes for the ACTH secretagogues corticotropin-releasing factor (CRF) and
      arginine vasopressin (AVP) is not clear. While investigating the neuroendocrine
      correlates of alcohol administration via different routes (intraperitoneal vs
      intragastric), we noted a difference in the time course of NGFI-B mRNA expression
      in the pPVN, despite comparable dynamics in ACTH secretion. By comparing the
      temporal cascade of transcriptional events in vivo after alcohol injection via
      either route, we sought to determine functional relationships between IEGs and
      the induction of CRF and AVP heteronuclear RNAs (hnRNAs). One advantage of our
      paradigm is the use of the same stimulus (systemic alcohol injection) in which
      access to the CNS does not differ between the groups to be compared.
      Intraperitoneal administration of the drug resulted in significant increases in c
      fos mRNA, Fos protein, CRF hnRNA, and AVP hnRNA. In contrast, intragastric
      treatment evoked a brief, modest elevation in c-fos mRNA and Fos protein,
      increased AVP hnRNA, and caused no detectable change in CRF hnRNA. These data
      indicate that robust increases in CRF hnRNA are closely linked to full expression
      of c-fos mRNA and Fos protein. In addition, the expression of NGFI-B after both
      routes of administration is indicative of cellular activation within the pPVN in
      parallel with secretion of ACTH.

PMID- 9592112
TI  - Behavioral discrimination between quinine and KCl is dependent on input from the
      seventh cranial nerve: implications for the functional roles of the gustatory
      nerves in rats.
AB  - The rat glossopharyngeal nerve (GL), which innervates posterior tongue taste
      buds, contains several physiologically defined taste fiber types; at least one
      type is primarily responsive to certain alkaloids (such as quinine), and another
      is primarily responsive to acids and salts. In contrast, the chorda tympani (CT),
      which innervates anterior tongue taste buds, does not appear to contain fibers
      that differentially respond to quinine relative to salts and acids. It was
      therefore predicted that GL transection should disrupt behavioral discriminations
      between quinine and either acids or salts. Water-restricted rats were trained to
      press one of two levers if a sampled taste stimulus was quinine (0.1-1.0 mM) and
      the second lever if the sampled stimulus was KCl (0.1-1.0 M). Sham surgery, GL
      transection, and sublingual and submaxillary salivary gland extirpation were
      found to have no effect relative to presurgical performance. Both CT transection
      and combined GL and CT transection caused a substantial and approximately equal
      decrement in discrimination performance. Removal of the gustatory branches of the
      seventh cranial nerve [CT and greater superficial petrosal (GSP)] nearly
      eliminated the discrimination of the taste stimuli, and combined transection of
      the CT, GL, and GSP unequivocally reduced performance to chance levels. Although
      these findings were not presaged by the known electrophysiology, they nonetheless
      compare favorably with other studies reporting little effect of GL transection on
      behavioral responses to quinine. These results, in the context of other
      discrimination studies reported in the literature, suggest that, in rats, the
      neural coding of taste quality depends primarily on the input of the facial
      nerve.

PMID- 9592113
TI  - Magnesium deficiency-dependent audiogenic seizures (MDDASs) in adult mice: a
      nutritional model for discriminatory screening of anticonvulsant drugs and
      original assessment of neuroprotection properties.
AB  - A great many animal models for audiogenic seizures have been described. The
      extent to which these models may provide insight into neuroscience fields such as
      abnormal locomotor behavior (wild running), seizures and anticonvulsants, and
      neuroinsults and neuroprotectors is examined here by our study of magnesium
      deficiency-dependent audiogenic seizures (MDDASs) in adult mice. MDDASs were
      induced in all of the eight tested adult murine strains and are presented as a
      sequence of four successive components (latency, wild running, convulsion, and
      recovery phase periods). Compared with several classic seizure tests, the
      nutritional MDDAS model responded to low doses of prototype antiepileptic drugs
      (AEDs), including phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB),
      valproic acid (VPA), ethosuximide (ESM), and diazepam (DZP). Modulation by AEDs
      of the four components of MDDAS indicated that this seizure test was
      discriminatory, distinguishing between phenytoinergic (PHT, CBZ), GABAergic (PB,
      VPA, DZP), and ethosuximide (ESM) compounds. Suitability of the MDDAS test for
      evaluation of neuroprotective compounds was also examined: it showed partial
      (melatonin) and complete (WEB2170, an anti-PAF agent) reduction of recovery phase
      by non-anticonvulsant doses of test compounds. These neuroprotective responses
      were compared with neuroprotective potentials determined in a model of neonatal
      cerebral injury induced by focal injection of ibotenate (a glutamate analog).
      WEB2170 and melatonin reduced the size of lesions in white matter, but only
      WEB2170 protected cortical plate against ibotenate-induced lesions. In addition
      to the original neuroprotective behavior of WEB2170, studies on the
      neuroprotectors also supported GABAergic anticonvulsant activity of melatonin in
      the MDDAS test.

PMID- 9592114
TI  - Axotomy upregulates the anterograde transport and expression of brain-derived
      neurotrophic factor by sensory neurons.
AB  - In addition to the known retrograde transport of neurotrophins, it is now evident
      that endogenous brain-derived neurotrophic factor (BDNF) is transported in the
      anterograde direction in peripheral and central neurons. We used a double
      ligation procedure that distinguishes between anterograde and retrograde flow to
      quantify the anterograde transport of endogenous neurotrophins and neuropeptides
      in the peripheral nervous system before and after axotomy. BDNF accumulation
      proximal to the ligation (anterograde transport) was twice that distal to the
      ligation (retrograde direction). Anterograde transport of nerve growth factor and
      neurotrophin-3 was not evident. Furthermore, BDNF anterograde transport increased
      3.5-fold within 24 hr after sciatic nerve injury or dorsal rhizotomy. Anterograde
      transport of substance P and calcitonin gene-related peptide decreased after
      peripheral nerve lesion, demonstrating that there was no generalized increase in
      anterograde transport. To determine the source of the anterogradely transported
      BDNF, we performed in situ hybridization in a variety of tissues before and after
      axotomy. Expression of BDNF mRNA in proximal nerve segments did not change with
      treatment, showing that the increased accumulation of BDNF was not a result of
      increased local synthesis. BDNF mRNA and protein were expressed by dorsal root
      ganglion sensory neurons but not by motor neurons. BDNF mRNA expression was
      increased 1 d after nerve injury, and BDNF protein was also increased twofold to
      threefold, suggesting that sensory neurons are the major contributing source of
      the increased BDNF traffic in the sciatic nerve. Our results suggest that
      increased anterogradely transported BDNF plays a role in the early neuronal
      response to peripheral nerve injury at sites distal to the cell body.

PMID- 9592115
TI  - Induction of a specific olfactory memory leads to a long-lasting activation of
      protein kinase C in the antennal lobe of the honeybee.
AB  - In this study we investigated the role of protein kinase C (PKC) in associative
      learning of Apis mellifera. Changes in PKC activity induced by olfactory
      conditioning were measured in the antennal lobes, a brain structure involved in
      associative learning. Multiple conditioning trials inducing a memory different
      from that induced by a single conditioning trial specifically cause an increase
      in PKC activity. This increase begins 1 hr after conditioning, lasts up to 3 d,
      and is attributable to an increased level of constitutive PKC. The increased
      level of constitutive PKC consists of an early proteolysis-dependent phase and a
      late phase that requires RNA and protein synthesis. Inhibition of the pathways
      resulting in constitutive PKC selectively impairs distinct phases of multiple
      trial induced memory. The inhibition of the proteolytic mechanism has an instant
      effect on an early phase of multiple-trial induced memory but does not affect
      acquisition and the late phase of memory. Blocking of the transient PKC
      activation during conditioning does not affect the induction of memory formation.
      Thus, the constitutive PKC in the antennal lobe seems to contribute to the early
      phase of memory that is induced by multiple-trial conditioning.

PMID- 9592116
TI  - Activation of coeruleospinal noradrenergic inhibitory controls during withdrawal
      from morphine in the rat.
AB  - We previously reported that withdrawal from morphine induces the expression of
      Fos, a marker of neuronal activity, in spinal cord neurons, particularly in
      laminae I and II of the superficial dorsal horn, and that the magnitude of Fos
      expression is increased in rats with a midthoracic spinal transection. We
      suggested that loss of withdrawal-associated increases in descending inhibitory
      controls that arise in the brainstem underlie the increased Fos expression after
      spinal transection. Here, we addressed the origin of the supraspinal inhibition.
      We injected rats intracerebroventricularly with saline or anti-dopamine-beta
      hydroxylase-saporin, a toxin that destroys noradrenergic neurons of the locus
      coeruleus. Eleven days later, we implanted rats with morphine or placebo pellets,
      and after 4 d, we precipitated withdrawal with naltrexone. One hour later, the
      rats were killed, their brains and spinal cords were removed, and transverse
      sections of the brains and spinal cords were immunoreacted with an antibody to
      Fos. In placebo-pelleted rats, the toxin injection did not alter behavior and did
      not induce expression of the Fos protein. However, compared with saline-injected
      withdrawing rats, the toxin-treated rats that underwent withdrawal demonstrated
      an intense withdrawal behavior rarely seen in the absence of toxin, namely
      forepaw fluttering. The rats also had significantly increased Fos-like
      immunoreactivity in all laminae of the cervical cord and in laminae I and II and
      the ventral horn of the lumbar cord. No differences were recorded in the sacral
      cord. We conclude that the effects of spinal transection in rats that withdraw
      from morphine in part reflect a loss of coeruleospinal noradrenergic inhibitory
      controls.

PMID- 9592117
TI  - Single-cell correlates of a representational boundary in rat somatosensory
      cortex.
AB  - In primary somatosensory cortex (S1), the transition from one representation to
      the next is typically abrupt when assayed physiologically. However, the extent of
      anatomical projections to and within the cortex do not strictly respect these
      physiologically defined transitions. Physiological properties, such as synaptic
      strengths or intracortical inhibition, have been hypothesized to account for the
      functionally defined precision of these representational borders. Because these
      representational borders can be translocated across the cortex by manipulations
      or behaviors that change the activity patterns of inputs to the cortex,
      understanding the physiological mechanisms that delimit representations is also
      an important starting point for understanding cortical plasticity. A novel in
      vivo and in vitro preparation has been developed to examine the cellular and
      synaptic mechanisms that underlie representational borders in the rat. In vivo, a
      short segment of the border between the forepaw-lower jaw representations in rat
      S1 was mapped using standard electrophysiological methods and was visibly marked
      using iontophoresis of pontamine sky blue dye. Slices were then obtained from
      this marked region and maintained in vitro. Intracellularly recorded responses to
      electrical stimulation of supragranular cortex were obtained from single neurons
      near the border in response to stimulation within the representational zone or
      across the border. Both excitatory and inhibitory responses were smaller when
      evoked by stimuli that activated projections that crossed borders, as compared
      with stimuli to projections that did not. These findings indicate that
      intracortical network properties are contributing to the expressions of
      representational discontinuities in the cortex.

PMID- 9592118
TI  - Perceptual correlates of changes in cortical representation of fingers in blind
      multifinger Braille readers.
AB  - The mature mammalian nervous system alters its functional organization in a use
      dependent manner. Enhanced stimulation of a body part enlarges its cortical
      representational zones and may change its topographic order. Little is known
      about the perceptual and behavioral relevance of these plastic alterations in
      cortical organization. We used blind Braille readers who use several fingers on
      each hand and who do so for many hours each day as a model to investigate this
      issue. Magnetic source imaging indicated that the cortical somatosensory
      representation of the fingers was frequently topographically disordered in these
      subjects; in addition, they frequently misperceived which of these fingers was
      being touched by a light tactile stimulus. In contrast, neither the disordered
      representation nor mislocalizations were observed in sighted controls. Blind non
      teacher Braille readers who used only one finger for reading were not
      significantly different from the sighted controls. Thus, use-dependent cortical
      reorganization can be associated with functionally relevant changes in the
      perceptual and behavioral capacities of the individual.

PMID- 9592119
TI  - Specificity of the N1 and N2 sialidase subtypes of human influenza A virus for
      natural and synthetic gangliosides.
AB  - Sialyl-linkage specificity of sialidases of the human influenza A virus strains,
      A/Aichi/2/68 (H3N2) and A/PR/8/34 (H1N1) were studied using natural and synthetic
      gangliosides. The sialidase of the A/Aichi/2/68 strain hydrolyzed the terminal
      Neu5Acalpha2-3Gal sequence but not the Neu5Acalpha2-3 linkage on the inner Gal of
      GM1a, which is a ganglioside that has the gangliotetraose chain (Galbeta1
      3GalNAcbeta1-4-(Neu5Acalpha2-3)Galbeta1++ +-4Glcbeta1-Cer). The sialidase
      hydrolyzed the Neu5Ac on the inner Gal of GM2, which had a shorter gangliotriose
      chain. GM4, which had the shortest chain (Neu5Acalpha2-3Galbeta1-Cer) of the
      gangliosides, had a lower substrate specificity. The N1 and N2 sialidase subtypes
      of the human influenza A virus had no significant variation in their substrate
      specificity for the gangliosides. Analysis of 11 synthetic gangliosides, which
      contained various ceramide or sialic acid moieties, demonstrated that
      A/Aichi/2/68 (H3N2) sialidase recognized the ceramide and sialic acid moiety and
      the length and structure of the sialyl sugar chain.

PMID- 9592120
TI  - Rapid and sensitive GC/MS characterization of glycolipid released Galalpha1,3Gal
      terminated oligosaccharides from small organ specimens of a single pig.
AB  - Pig to human xenotransplantation is considered a possible solution to the
      prevailing chronic lack of human donor organs for allotransplantation. The
      Galalpha1,3Gal determinant is the major porcine xenogeneic epitope causing
      hyperacute rejection following human antibody binding and complement activation.
      In order to characterize the tissue distribution of Galalpha1,3Gal-containing and
      blood group-type glycosphingolipids in pig, acid and nonacid glycosphingolipids
      were isolated from the kidney, small intestine, spleen, salivary gland, liver,
      and heart of a single pig obtained from a semi-inbred strain homozygous at the
      SLA locus. Glycolipids were analyzed by thin-layer immunostaining using
      monoclonal antibodies, and following ceramide glycanase cleavage as permethylated
      oligosaccharides by gas chromatography, gas chromatography-mass spectrometry, and
      matrix-assisted laser desorption/ionization mass spectrometry. The kidney
      contained large amounts of Galalpha1,3Gal-containing penta- and hexasaccharides
      having carbohydrate sequences consistent with the Galalpha1,3nLc4and
      Galalpha1,3Lexstructures, respectively. The former structure was tentatively
      identified in all organs by GC/MS. The presence of extended Galalpha1,3Gal
      terminated structures in the kidney and heart was suggested by antibody binding,
      and GC/MS indicated the presence of a Galalpha1,3nLc6structure in the heart. The
      kidney, spleen, and heart contained blood group H pentaglycosylceramides based on
      type 1 (H-5-1) and type 2 (H-5-2) chains, and H hexaglycosylceramides based on
      the type 4 chain (H-6-4). In the intestine H-5-1 and H-6-4 were expressed, in the
      salivary gland H-5-1 and H-5-2, whereas only the H-5-1 structure was identified
      in the liver. Blood group A structures were identified in the salivary gland and
      the heart by antibody binding and GC/MS, indicating an organ-specific expression
      of blood group AH antigens in the pig.

PMID- 9592121
TI  - Genomic organization and chromosomal localization of three members of the UDP-N
      acetylgalactosamine: polypeptide N-acetylgalactosaminyltransferase family.
AB  - A homologous family of UDP- N -acetylgalactosamine: polypeptide N 
      acetylgalactosaminyltransferases (GalNAc-transferases) initiate O-glycosylation.
      These transferases share overall amino acid sequence similarities of
      approximately 45-50%, but segments with higher similarities of approximately 80%
      are found in the putative catalytic domain. Here we have characterized the
      genomic organization of the coding regions of three GalNAc-transferase genes and
      determined their chromosomal localization. The coding regions of GALNT1 , -T2 ,
      and -T3 were found to span 11, 16, and 10 exons, respectively. Several
      intron/exon boundaries were conserved within the three genes. One conserved
      boundary was shared in a homologous C. elegans GalNAc-transferase gene.
      Fluorescence in situ hybridization showed that GALNT1 , -T2 , and -T3 are
      localized at chromosomes 18q12-q21, 1q41-q42, and 2q24-q31, respectively. These
      results suggest that the members of the polypeptide GalNAc-transferase family
      diverged early in evolution from a common ancestral gene through gene
      duplication.

PMID- 9592122
TI  - Characterization of the lipid-carrier involved in the synthesis of
      enterobacterial common antigen (ECA) and identification of a novel
      phosphoglyceride in a mutant of Salmonella typhimurium defective in ECA
      synthesis.
AB  - The polysaccharide chains of enterobacterial common antigen (ECA) consist of
      linear trisaccharide repeat units with the structure -->3)-alpha-d-Fuc4NAc-(1-
      >4)-beta-d-ManNAcA-(1--> 4)-alpha-d-GlcNAc-(1-->, where Fuc4NAc is 4-acetamido-4,
      6-dideoxy-d-galactose, ManNAcA is N -acetyl-d- mannosaminuronic acid, and GlcNAc
      is N -acetyl-d-glucosamine. The major form of ECA (ECAPG) consists of
      polysaccharide chains that are believed to be covalently linked to diacylglycerol
      through phosphodiester linkage; the phospholipid moiety functions to anchor
      molecules in the outer membrane. The ECA trisaccharide repeat unit is assembled
      as a polyisoprenyl-linked intermediate which has been tentatively identified as
      Fuc4NAc-ManNAcA-GlcNAc-pyrophosphorylundecaprenol (lipid III). Subsequent chain
      elongation presumably occurs by a block-polymerization mechanism. However, the
      identity of the polyisoprenoid carrier-lipid has not been established.
      Accordingly, the current studies were conducted in an effort to structurally
      characterize the polyisoprenyl lipid-carrier involved in ECA synthesis. Isolation
      and characterization of the lipid carrier was facilitated by the accumulation of
      a ManNAcA-GlcNAc-pyrophosphorylpolyisoprenyl lipid (lipid II) in mutants of
      Salmonella typhimurium defective in the synthesis of TDP-Fuc4NAc, the donor of
      Fuc4NAc residues for ECA synthesis. Analyses of lipid II preparations by fast
      atom bombardment tandem mass spectroscopy (FAB-MS/MS) resulted in the
      identification of the lipid-carrier as the 55-carbon polyisoprenyl alcohol,
      undecaprenol. These analyses also resulted in the identification of a novel
      glycolipid which copurified with lipid II. FAB-MS/MS analyses of this glycolipid
      revealed its structure to be 1,2-diacyl- sn -glycero-3-pryophosphoryl-GlcNAc
      ManNAcA (DGP-disaccharide). An examination of purified ECAPGby phosphorus-31
      nuclear magnetic resonance spectroscopy confirmed that the polysaccharide chains
      are linked to diacylglycerol through phosphodiester linkage. Thus, DGP
      disaccharide does not appear to be an intermediate in ECAPGsynthesis.
      Nevertheless, although the available evidence clearly indicate that lipid II is a
      precursor of DGP-disaccharide, the function of this novel glycolipid is not yet
      known, and it may be an intermediate in the biosynthesis of a molecule other than
      ECAPG.

PMID- 9592123
TI  - NMR investigations of protein-carbohydrate interactions: refined three
      dimensional structure of the complex between hevein and methyl beta-chitobioside.
AB  - The specific interaction of hevein with GlcNAc-containing oligosaccharides has
      been analyzed by1H-NMR spectroscopy. The association constants for the binding of
      hevein to a variety of ligands have been estimated from1H-NMR titration
      experiments. The association constants increase in the order GlcNAc-alpha(1-->6)
      Man < GlcNAc < benzyl-beta-GlcNAc < p-nitrophenyl-beta-GlcNAc < chitobiose < p
      nitrophenyl-beta-chitobioside < methyl-beta-chitobioside < chitotriose. Entropy
      and enthalpy of binding for different complexes have been obtained from van't
      Hoff analysis. The driving force for the binding process is provided by a
      negative DeltaH0which is partially compensated by negative DeltaS0. These
      negative signs indicate that hydrogen bonding and van der Waals forces are the
      major interactions stabilizing the complex. NOESY NMR experiments in water
      solution provided 475 accurate protein proton-proton distance constraints after
      employing the MARDIGRAS program. In addition, 15 unambiguous protein/carbohydrate
      NOEs were detected. All the experimental constraints were used in a refinement
      protocol including restrained molecular dynamics in order to determine the highly
      refined solution conformation of this protein-carbohydrate complex. With regard
      to the NMR structure of the free protein, no important changes in the protein
      nOe's were observed, indicating that carbohydrate-induced conformational changes
      are small. The average backbone rmsd of the 20 refined structures was 0.055 nm,
      while the heavy atom rmsd was 0.116 nm. It can be deduced that both hydrogen
      bonds and van der Waals contacts confer stability to the complex. A comparison of
      the three-dimensional structure of hevein in solution to those reported for wheat
      germ agglutinin (WGA) and hevein itself in the solid state has also been
      performed. The polypeptide conformation has also been compared to the NMR-derived
      structure of a smaller antifungical peptide, Ac-AMP2.

PMID- 9592124
TI  - Short chain oligogalacturonides induce ethylene production and expression of the
      gene encoding aminocyclopropane 1-carboxylic acid oxidase in tomato plants.
AB  - Oligogalacturonic acids (OGAs), derived from plant cell wall pectin, have been
      implicated in a number of signal transduction pathways involved in growth,
      development and defense responses of higher plants. This study investigates the
      size range of OGAs capable of inducing ethylene synthesis in tomato plants, and
      demonstrates that in contrast with many other effects, only short chain OGAs are
      active. Oligomers across a range of DP from 2-15 were separated and purified to
      homogeneity by QAE-Sephadex anion exchange chromatography using a novel elution
      system. The OGAs were applied to tomato plants and assayed for their ability to
      induce ethylene gas release and changes in steady state levels of mRNA encoding
      the ethylene forming enzyme aminocyclopropane-1-carboxylic acid oxidase (ACO).
      The study demonstrated that only OGAs in the size range of DP4-6 were active both
      in eliciting ACO expression and in the production of ethylene.

PMID- 9592125
TI  - Molecular cloning, chromosomal mapping and tissue-specific expression of a novel
      human alpha1,2-mannosidase gene involved in N-glycan maturation.
AB  - Class I alpha1,2-mannosidases play an essential role in the elaboration of
      complex and hybrid N -glycans in mammalian cells. Using degenerate primers based
      on amino acid sequences conserved in all members of this enzyme family for RT
      PCR, two distinct PCR products were obtained from placenta and lymphocyte cDNAs.
      One of these was related to the previously cloned human and murine alpha1, 2
      mannosidase IA whereas the other was very similar to murine alpha1, 2-mannosidase
      IB. Northern blot analysis of human tissues with these two alpha1,2-mannosidase
      probes revealed very different patterns of tissue-specific expression. Similar
      tissue-specific expression of alpha1,2-mannosidase IA and IB was also observed on
      Northern blots of adult mouse tissues. A human placenta cDNA library was screened
      and PCR of brain, placenta, and lymphocyte cDNAs was performed in order to
      isolate the human alpha1,2-mannosidase IB cDNA. This cDNA encodes a type II
      membrane protein of 73 kDa that is 94% identical in amino acid sequence to the
      murine alpha1,2-mannosidase IB (Herscovics et al., 1994, J. Biol. Chem., 269,
      9864-9871). A truncated soluble form of the human alpha1,2-mannosidase IB lacking
      its N -terminal transmembrane domain was expressed as a secreted protein in
      Pichia pastoris . The recombinant enzyme was incubated with [3H]Man9GlcNAc and
      [3H]Man8GlcNAc (isomer B), and high performance liquid chromatography analysis of
      the products showed that [3H]Man9GlcNAc was readily converted to [3H]Man6GlcNAc
      and much more slowly to [3H]Man5GlcNAc, whereas [3H]Man8GlcNAc was rapidly
      trimmed to [3H]Man5GlcNAc. The human alpha1,2-mannosidase IB gene was isolated
      from a P1 human genomic library and shown to be at least 60 kb in size and to
      contain at least 13 exons. The gene was localized by fluorescence in situ
      hybridization to human chromosome 1p13, a region that undergoes many aberrations
      in various types of human cancers. These results show that there are at least two
      Class I alpha1,2-mannosidases in the human and murine genomes with very distinct
      transcriptional regulation in different tissues.

PMID- 9592126
TI  - Nerve growth factor-induced neurite formation in PC12 cells is independent of
      endogenous cellular gangliosides.
AB  - The PC12 rat pheochromocytoma cell line is an established model for nerve growth
      factor (NGF)-induced neurite formation. It has been shown that when gangliosides
      are added to the culture medium of PC12 cells, NGF-induced neurite formation of
      PC12 cells is enhanced. To determine the role of endogenous cellular gangliosides
      themselves in NGF-elicited neurite formation, we depleted cellular gangliosides
      using the new specific glucosylceramide synthase inhibitor, d, l-threo-1-phenyl-2
      hexadecanoylamino-3-pyrrolidino-1-propanol.HCl (PPPP). 0.5-2 microM PPPP rapidly
      inhibited ganglioside synthesis and depletedcellular gangliosides. Nonetheless,
      over a concentration range of 5-100 ng/ml NGF, in both low serum and serum-free
      medium, neurite formation was normal. Even pretreatment of PC12 cells for up to 6
      days with 1 microM PPPP followed by cotreatment with PPPP and NGF for 10 days,
      still did not inhibit neurite formation. The conclusion that ganglioside
      depletion did not block neurite formation stimulated by NGF was supported by the
      lack of effect of PPPP, under these same conditions, on cellular acetylcholine
      esterase activity, a neuronal differentiation marker (73.8 +/- 12.1 versus 67.2
      +/- 4.6 nmol/min/mg protein at 50 ng/ml NGF; control versus 1 microM PPPP). These
      findings, together with previous studies showing enhancement of NGF-induced
      neurite formation by exogenous gangliosides, underscore the vastly different
      effects that exogenous gangliosides and endogenous gangliosides may have upon
      cellular functions.

PMID- 9592127
TI  - Fucosyltransferase activities in human pancreatic tissue: comparative study
      between cancer tissues and established tumoral cell lines.
AB  - Human pancreatic cancer is characterized by an alteration in fucose-containing
      surface blood group antigens such as H antigen, Lewis b, Lewis y, and sialyl
      Lewis. These carbohydrate determinants can be synthesized by sequential action of
      alpha(2,3) sialyltransferases or alpha(1,2) fucosyltransferases (Fuc-T) and
      alpha(1,3/1,4) fucosyltransferases on (poly)N-acetyllactosamine chains.
      Therefore, the expression and the function of seven fucosyltransferases were
      investigated in normal and cancer pancreatic tissues and in four pancreatic
      carcinoma cell lines. Transcripts of FUT1, FUT2, FUT3, FUT4, FUT5, and FUT7 were
      detected by RT-PCR in carcinoma cell lines as well as in normal and tumoral
      tissues. Interestingly, the FUT6 message was only detected in tumoral tissues.
      Analysis of the acceptor substrate specificity for fucosyltransferases indicated
      that alpha(1,2) Fuc-T, alpha(1,3) Fuc-T, and alpha(1,4) Fuc-T were expressed in
      microsome preparations of all tissues as demonstrated by fucose incorporation
      into phenyl beta-d-galactoside, 2'-fucosyllactose, N-acetyllactosamine, 3'-sialyl
      N-acetyllactosamine, and lacto-N-biose. However, these fucosyltransferase
      activities varied between tissues. A substantial decrease of alpha(1,2) Fuc-T
      activity was observed in tumoral tissues and cell lines compared to normal
      tissues. Conversely, the activity of alpha(1,4) Fuc-T, which generates Lewis a
      and sialyl-Lewis a structures, and that of alpha(1,3) Fuc-T, able to generate a
      lactodifucotetraose structure, were very important in SOJ-6 and BxPC-3 cell
      lines. These increases correlated with an enhanced expression of Lewis a, sialyl
      Lewis a, and Lewis y on the cell surface. The activity of alpha(1,3) Fuc-T, which
      participates in the synthesis of the sialyl-Lewis x structure, was not
      significantly modified in cell lines compared to normal tissues. However, the
      sialyl-Lewis x antigen was expressed preferentially on the surface of SOJ-6 and
      BxPC-3 cell lines but was not detected on Panc-1 and MiaPaca-2 cell lines
      suggesting that several alpha(1,3) Fuc-T might be involved in sialyl-Lewis x
      synthesis.

PMID- 9592128
TI  - Expression of Lex antigen in Schistosoma japonicum and S.haematobium and immune
      responses to Lex in infected animals: lack of Lex expression in other trematodes
      and nematodes.
AB  - Adults of the human parasitic trematode Schistosoma mansoni, which causes
      hepatosplenic/intestinal complications in humans, synthesize glycoconjugates
      containing the Lewis x (Lex) Galbeta1-->4(Fucalpha1-->3)GlcNAcbeta1-->R, but not
      sialyl Lewis x (sLex), antigen. We now report on our analyses of Lexand
      sLexexpression in S.haematobium and S.japonicum, which are two other major
      species of human schistosomes that cause disease, and the possible autoimmunity
      to these antigens in infected individuals. Antigen expression was evaluated by
      both ELISA and Western blot analyses of detergent extracts of parasites using
      monoclonal antibodies. Several high molecular weight glycoproteins in both S.
      haematobium and S. japonicum contain the Lexantigen, but no sialyl Lexantigen was
      detected. In addition, sera from humans and rodents infected with S.haematobium
      and S.japonicum contain antibodies reactive with Lex. These results led us to
      investigate whether Lexantigens are expressed in other helminths, including the
      parasitic trematode Fasciola hepatica , the parasitic nematode Dirofilaria
      immitis (dog heartworm), the ruminant nematode Haemonchus contortus , and the
      free-living nematode Caenorhabditis elegans . Neither Lexnor sialyl-Lexis
      detectable in these other helminths. Furthermore, none of the helminths,
      including schistosomes, express Lea, Leb, Ley, or the H-type 1 antigen. However,
      several glycoproteins from all helminths analyzed are bound by Lotus
      tetragonolobus agglutinin , which binds Fucalpha1-->3GlcNAc, and Wisteria
      floribunda agglutinin, which binds GalNAcbeta1-->4GlcNAc (lacdiNAc or LDN). Thus,
      schistosomes may be unique among helminths in expressing the Lexantigen, whereas
      many different helminths may express alpha1,3-fucosylated glycans and the LDN
      motif.

PMID- 9592129
TI  - Conserved sequences in enzymes of the UDP-GlcNAc/MurNAc family are essential in
      hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase.
AB  - The UDP-GlcNAc/MurNAc family of eukaryotic and prokaryotic enzymes use UDP-GlcNAc
      or UDP-MurNAc-pentapeptide as donors, dolichol-P or polyprenol-P as acceptors,
      and generate sugar-P-P-polyisoprenols. A series of six conserved sequences,
      designated A through F and ranging from 5 to 13 amino acid residues, has been
      identified in this family. To determine whether these conserved sequences are
      required for enzyme function, various mutations were examined in hamster UDP
      GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT). Scramble mutations of sequences B
      F, generated by scrambling the residues within each sequence, demonstrated that
      each is important in GPT. While E and F scrambles appeared to prevent stable
      expression of GPT, scrambling of B-D resulted in GPT mutants that could be stably
      expressed and bound tunicamycin, but lacked enzymatic activity. Further, the C
      and D scramble mutants had an unexpected sorting defect. Replacement of sequences
      B-F with prokaryotic counterparts from either the B.subtilis mraY or E.coli rfe
      genes also affected GPT by preventing expression of the mutant protein (B, F) or
      inhibiting its enzymatic activity (C-E). For the C-E replacements, no acquisition
      of acceptor activity for polyprenol-P, the fully unsaturated natural bacterial
      acceptor, was detected. These studies show that the conserved sequences of the
      UDP-GlcNAc/MurNAc family are important, and that the eukaryotic and prokaryotic
      counterparts are not freely interchangeable. Since several mutants were
      efficiently expressed and bound tunicamycin, yet lacked enzymatic activity, the
      data are consistent with these sequences having a direct role in product
      formation.

PMID- 9592130
TI  - High-level expression of the Endo-beta-N-acetylglucosaminidase F2 gene in E.coli:
      one step purification to homogeneity.
AB  - The Endo F2gene was overexpressed in E.coli as a fusion protein joined to the
      maltose-binding protein. MBP-Endo F2was found in a highly enriched state as
      insoluble, inactive inclusion bodies. Extraction of the inclusion bodies with 20%
      acetic acid followed by exhaustive dialysis rendered the fusion protein active
      and soluble. MBP-Endo F2was digested with Factor Xaand purified on Q-Sepharose.
      The enzyme was homogeneous by SDS-PAGE, and appeared as a single symmetrical peak
      on HPLC. Analysis of the amino-terminus demonstrated conclusively that
      recombinant Endo F2was homogeneous and identical to the native enzyme.

PMID- 9592131
TI  - Modeling and analysis of competitive RT-PCR.
AB  - The present studies demonstrate a theoretical and practical framework for the
      accurate quantitation of gene expression in RNA extracted from microscopic tissue
      samples. The approaches are developed around competitive RT-PCR techniques. Assay
      performance has been examined and validated at both the RT and PCR steps. Our
      analysis of RT transcription efficiency for a number of native and competitor
      combinations shows that this property can differ, even for very similar
      templates. However, this difference is consistent and, once identified and
      measured, can be removed as an obstacle to accuracy. Using mathematical modeling,
      we have examined the simulated co-amplification of native and competitor
      templates in PCR. Useful insights have emerged from such modeling which indicate
      that differences in initial amplification efficiency and the rate of decay of
      amplification efficiency during the reaction can rapidly lead to inaccuracy, even
      while the slope and linearity of log plots of the competitor input and reaction
      product ratios are close to ideal. Finally, we show here that competitive RT-PCR
      reactions do not have to remain in the log-linear phase of PCR in order to
      accomplish accurate and precise quantification. Using appropriate competitors
      sharing primer binding sites and high internal sequence similarity, identical
      amplification efficiencies are preserved throughout the reaction. Reaction
      products, including heteroduplexes formed between native and competitor templates
      as reactions progress to plateau, can be identified and quantified accurately
      using the new technique of denaturing HPLC (dHPLC). This analytical technique
      allows the accuracy of competitive RT-PCR to be preserved beyond the linear
      phase. The technique has high sensitivity and precision and target abundances as
      low as 100 copies could be reliably estimated.

PMID- 9592132
TI  - The environment of 5S rRNA in the ribosome: cross-links to the GTPase-associated
      area of 23S rRNA.
AB  - Two photoreactive diazirine derivatives of uridine were used to study contacts
      between 5S rRNA and 23 rRNA in situ in Escherichia coli ribosomes. 2'-Amino-2'
      deoxy-uridine or 5-methyleneaminouridine were introduced into 5S rRNA by T7
      transcription. After incorporation of these uridine analogues into the transcript
      their amino groups were modified with 4-[3-(trifluoromethyl)-3 H -diazirin-3
      yl]benzyl isothiocyanate or the N -hydroxysuccinimide ester of 4-[3
      (trifluoromethyl)-3 H -diazirin-3-yl]benzoic acid respectively. 5S rRNA carrying
      the photoreactive diazirine groups (referred to as the 2'-aminoribose derivative
      and the 5-methyleneamino derivative respectively) was reconstituted into 50S
      subunits or 70S ribosomes. After mild UV irradiation cross-links formed to 23S
      rRNA were analysed by standard procedures. All of the observed cross-links
      involved residue U89 of the 5S rRNA. Three nucleotides of 23S rRNA were cross
      linked to this residue with the 5-methyleneamino derivative, namely U958, G1022
      and G1138. With the 2'-aminoribose derivative a single cross-link was found, to
      U958. The significance of these cross-links for our understanding of the
      structure and function of 5S rRNA and its environment in the ribosome are
      discussed.

PMID- 9592133
TI  - Unique translational positioning of nucleosomes on synthetic DNAs.
AB  - A computational study was previously carried out to analyze DNA sequences that
      are known to position histone octamers at single translational sites. A conserved
      pattern of intrinsic DNA curvature was uncovered that was proposed to direct the
      formation of nucleosomes to unique positions. The pattern consists of two regions
      of curved DNA separated by preferred lengths of non-curved DNA. In the present
      study, 11 synthetic DNAs were constructed which contain two regions of curved DNA
      of the form [(A5.T5)(G/C)5]4 separated by non-curved regions of variable length.
      Translational mapping experiments of in vitro reconstituted mononucleosomes using
      exonuclease III, micrococcal nuclease and restriction enzymes demonstrated that
      two of the fragments positioned nucleosomes at a single site while the remaining
      fragments positioned octamers at multiple sites spaced at 10 base intervals. The
      synthetic molecules that positioned nucleosomes at a single site contain non
      curved central regions of the same lengths that were seen in natural nucleosome
      positioning sequences. Hydroxyl radical and DNase I digests of the synthetic DNAs
      in reconstituted nucleosomes showed that the synthetic curved element on one side
      of the nucleosomal dyad assumed a rotational orientation where narrow minor
      grooves of the A-tracts faced the histone surface with all molecules. In
      contrast, the curved element on the other side of the nucleosome displayed
      variable rotational orientations between molecules which appeared to be related
      to the positioning effect. These results suggest that asymmetry between the two
      halves of nucleosomal DNA may facilitate translational positioning.

PMID- 9592135
TI  - Distinct regions of U3 snoRNA interact at two sites within the 5' external
      transcribed spacer of pre-rRNAs in Trypanosoma brucei cells.
AB  - U3 snoRNA is required for early pre-rRNA processing events that include cleavage
      of the 5' external transcribed spacer (5'ETS) and 18S rRNA maturation. Herein,
      psoralen RNA crosslinking has been used to indicate novel in vivo interactions
      between the minimally-sized Trypanosoma brucei U3 snoRNA and pre-rRNAs. Two
      discrete U3 crosslinks were mapped to 5'ETS sequences, then individually isolated
      by hybrid selection following digestion of pre-rRNAs. Crosslink positions within
      these U3-site1 and U3-site2 complexes were resolved by RNaseH digestion and
      primer extension analyses. Hinge bases of U3 contacted site1 bases U140 and U142
      just 3' of the processed primary site. This is the first experimental evidence of
      a U3 RNA interaction adjacent to a major 5'ETS cleavage site and supports a
      critical role for U3 in its processing. Highly conserved box A bases contacted
      site2 base U945, 187 nt upstream of 18S-like rRNA sequences. Site2 sequences are
      not required for primary processing, thus, a U3 interaction here might have roles
      in subsequent downstream processing events. These results clearly demonstrated
      that distinct U3 snoRNA sequences crosslinked different regions of the 5'ETS and
      support a model for U3 as a multifunctional snoRNA.

PMID- 9592134
TI  - Dnmt2 is not required for de novo and maintenance methylation of viral DNA in
      embryonic stem cells.
AB  - We have shown previously that de novo methylation activities persist in mouse
      embryonic stem (ES) cells homozygous for a null mutation of Dnmt1 that encodes
      the major DNA cytosine methyltransferase. In this study, we have cloned a
      putative mammalian DNA methyltransferase gene, termed Dnmt2 , that is homologous
      to pmt1 of fission yeast. Different from pmt1 in which the catalytic Pro-Pro-Cys
      (PPC) motif is 'mutated' to Pro-Ser-Cys, Dnmt2 contains all the conserved
      methyltransferase motifs, thus likely encoding a functional cytosine
      methyltransferase. However, baculovirus-expressed Dnmt2 protein failed to
      methylate DNA in vitro . To investigate whether Dnmt2 functions as a DNA
      methyltransferase in vivo , we inactivated the Dnmt2 gene by targeted deletion of
      the putative catalytic PPC motif in ES cells. We showed that endogenous virus was
      fully methylated in Dnmt2 -deficient mutant ES cells. Furthermore, newly
      integrated retrovirus DNA was methylated de novo in infected mutant ES cells as
      efficiently as in wild-type cells. These results indicate that Dnmt2 is not
      essential for global de novo or maintenance methylation of DNA in ES cells.

PMID- 9592136
TI  - DNA sequence analysis by MALDI mass spectrometry.
AB  - Conventional DNA sequencing is based on gel electrophoretic separation of the
      sequencing products. Gel casting and electrophoresis are the time limiting steps,
      and the gel separation is occasionally imperfect due to aberrant mobility of
      certain fragments, leading to erroneous sequence determination. Furthermore,
      illegitimately terminated products frequently cannot be distinguished from
      correctly terminated ones, a phenomenon that also obscures data interpretation.
      In the present work the use of MALDI mass spectrometry for sequencing of DNA
      amplified from clinical samples is implemented. The unambiguous and fast
      identification of deletions and substitutions in DNA amplified from heterozygous
      carriers realistically suggest MALDI mass spectrometry as a future alternative to
      conventional sequencing procedures for high throughput screening for mutations.
      Unique features of the method are demonstrated by sequencing a DNA fragment that
      could not be sequenced conventionally because of gel electrophoretic band
      compression and the presence of multiple non-specific termination products.
      Taking advantage of the accurate mass information provided by MALDI mass
      spectrometry, the sequence was deduced, and the nature of the non-specific
      termination could be determined. The method described here increases the fidelity
      in DNA sequencing, is fast, compatible with standard DNA sequencing procedures,
      and amenable to automation.

PMID- 9592137
TI  - Sticky egyptians: a technique for assembling genes encoding constrained peptides
      of variable length.
AB  - Naturally occurring peptides, such as those produced by the poisonous marine
      snails of the genus Conus , have the ability to form tight, highly specific
      molecular interactions. The rigidity of the peptide framework which promotes
      these interactions is usually maintained by disulphide bonds, and it seems that
      the overall main chain conformation (or fold) of the peptide is determined by its
      length and the sequence distribution of the pairs of cysteine residues
      participating in these bonds. The fold of the peptide in turn is largely
      responsible for its shape. Since highly effective molecular interactions occur
      between species complementary in shape, we reasoned that peptides with the
      greatest potential in therapy or diagnosis would be found in a library of shapes,
      those peptides with a shape complementary to a given target being identified, for
      example, by selection. As a first step towards constructing such a peptide shape
      library, we have developed a method for assembling DNA fragments which encode an
      even number of cysteine residues and which are of variable length. We describe
      this method here.

PMID- 9592138
TI  - RNA heptamers that direct RNA cleavage by mammalian tRNA 3' processing
      endoribonuclease.
AB  - Mammalian tRNA 3' processing endoribonuclease (3' tRNase) can recognize and
      cleave any target RNA that forms a precursor tRNA-like complex with another RNA.
      Various sets of RNA molecules were tested to identify the smallest RNA that can
      direct target RNA cleavage by 3' tRNase. A 3' half tRNAArgwas cleaved efficiently
      by 3' tRNase in the presence of small 5' half tRNAArgvariants, the D stem-loop
      region of which was partially deleted. Remarkably, 3' tRNase also cleaved the 3'
      half tRNAArgin the presence of a 7 nt 5' tRNAArg composed only of the acceptor
      stem region with a catalytic efficiency comparable with that of cleavage directed
      by an intact 5' half tRNAArg. The catalytic efficiency of cleavage directed by
      the heptamer decreased as the stability of the T stem-loop structures of 3' half
      tRNAArg variants decreased. No heptamer-directed cleavage of a 3' half tRNAArg
      without T stem base pairs was detected. A heptamer also directed cleavage of an
      HIV-1 RNA containing a stable hairpin structure. These findings suggest that in
      the presence of an RNA heptamer, 3' tRNase can discriminate and eliminate target
      RNAs that possess a stable hairpin adjacent to the heptamer binding sequence from
      a large complex RNA pool.

PMID- 9592141
TI  - A method for analyzing the qualitative and quantitative aspects of gene
      expression: a transcriptional profile revealed for HeLa cells.
AB  - A number of strategies have been devised by which differentially expressed genes
      in different cell types or tissues can be identified. We here report an efficient
      method to analyze the qualitative and quantitative aspects of transcripts and to
      construct an extensive gene expression profile in any kind of cell or tissue of
      interest. This method enables us to analyze the composition of mRNA species,
      reflecting gene activities, by measuring the frequency of appearance of
      concatamerized 17mer cDNA mini-fragments, which are proportional to the abundance
      of mRNA. As compared with a related method previously described by others, we can
      analyze approximately 3-4 bp longer cDNA fragments derived from amounts of total
      RNA as small as 1 microg. Using this technique we examined 10 100 cDNA mini
      fragments from HeLa cells and constructed a gene expression profile consisting of
      3665 genes. This method should thus provide an overall indication of gene
      activities and a rational means for monitoring gene fluctuation in different
      cells or tissues at different stages of development, in normal and disease
      states.

PMID- 9592139
TI  - SCP2: a major protein component of the axial elements of synaptonemal complexes
      of the rat.
AB  - In the axial elements of synaptonemal complexes (SCs) of the rat, major protein
      components have been identified, with relative electrophoretic mobilities (M rs)
      of 30 000-33 000 and 190 000. Using monoclonal anti-SC antibodies, we isolated
      cDNA fragments which encode the 190 000 M r component of rat SCs. The translation
      product predicted from the nucleotide sequence of the cDNA, called SCP2 (for
      synaptonemal complex protein 2), is a basic protein (pI = 8.0) with a molecular
      mass of 173 kDa. At the C-terminus, a stretch of approximately 50 amino acid
      residues is predicted to be capable of forming coiled-coil structures. SCP2
      contains two clusters of S/T-P motifs, which are common in DNA-binding proteins.
      These clusters flank the central, most basic part of the protein (pI = 9.5).
      Three of the S/T-P motifs are potential target sites for p34(cdc2) protein
      kinase. In addition, SCP2 has eight potential cAMP/cGMP-dependent protein kinase
      target sites. The gene encoding SCP2 is transcribed specifically in the testis,
      in meiotic prophase cells. At the amino acid sequence and secondary structural
      level, SCP2 shows some similarity to the Red1 protein, which is involved in
      meiotic recombination and the assembly of axial elements of SCs in yeast. We
      speculate that SCP2 is a DNA-binding protein involved in the structural
      organization of meiotic prophase chromosomes.

PMID- 9592140
TI  - Function of the C-terminal transactivation domain of human heat shock factor 2 is
      modulated by the adjacent negative regulatory segment.
AB  - DNA binding of heat shock factor 2 (HSF2) is induced during hemin-induced
      differentiation of human erythroleukemia cell line K562. To identify the
      transcriptional activation and the regulatory domains of HSF2, we constructed a
      series of deletion derivatives fused to the yeast GAL4 DNA binding domain and
      analyzed their transactivation activity. A minimal transactivation domain of HSF2
      was localized to the C-terminus (residues 472-536), as in HSF1, although amino
      acid sequence similarity for these regions was rather limited and the potential
      transactivation ability was about 25% that of HSF1. The transactivation mediated
      by this region of HSF2 was found to be negatively regulated by the adjacent 18
      amino acid segment (residues 428-445) under normal conditions. Furthermore, the
      latter segment, when fused to the GAL4 activation domain, markedly inhibited GAL4
      activity. Extract containing most derivatives of HSF2 retaining this segment
      exhibited doublet or triplet bands in gel mobility shift assays with heat shock
      element-containing DNA, suggesting possible involvement of some factors
      interacting with that segment in the negative regulation. Another putative
      transactivation domain and two negative regulatory regions were also localized
      within the internal region.

PMID- 9592142
TI  - Exonuclease IX of Escherichia coli.
AB  - The bacteria Escherichia coli contains several exonucleases acting on both double
      and single-stranded DNA and in both a 5'-->3' and 3'-->5' direction. These
      enzymes are involved in replicative, repair and recombination functions. We have
      identified a new exonuclease found in E.coli, termed exonuclease IX, that acts
      preferentially on single-stranded DNA as a 3'-->5' exonuclease and also functions
      as a 3'-phosphodiesterase on DNA containing 3'-incised apurinic/apyrimidinic (AP)
      sites to remove the product trans -4-hydroxy-2-pentenal 5-phosphate. The enzyme
      showed essentially no activity as a deoxyribophosphodiesterase acting on 5'
      incised AP sites. The activity was isolated as a glutathione S-transferase fusion
      protein from a sequence of the E.coli genome that was 60% identical to a 260 bp
      region of the small fragment of the DNA polymerase I gene. The protein has a
      molecular weight of 28 kDa and is free of AP endonuclease and phosphatase
      activities. Exonuclease IX is expressed in E.coli , as demonstrated by reverse
      transcription-PCR, and it may function in the DNA base excision repair and other
      pathways.

PMID- 9592143
TI  - Single point mutations located outside the inter-monomer domains abolish
      trimerization of Schizosaccharomyces pombe PCNA.
AB  - We have generated proliferating cell nuclear antigen (PCNA) mutants by low
      fidelity PCR and screened for lethal mutations by testing for lack of
      complementation of a Schizosaccharomyces pombe strain disrupted for the pcn1 +
      gene. We thus identified eight lethal mutants out of the 50 cDNAs tested. Six
      were truncated in their C-terminal region due to the introduction of a stop codon
      within their coding sequences. Two were full-length with a single point mutation
      at amino acid 68 or 69. The two latter mutants were overexpressed in insect cells
      via a recombinant baculovirus and were purified. They were unable to stimulate
      DNA polymerase delta DNA replication activity on a poly(dA).oligo(dT) template.
      Cross-linking experiments showed that this was due to their inability to form
      trimers. Since these two mutations are adjacent and not located in a domain of
      the protein putatively involved in inter-monomer interactions, our results show
      that the beta-sheet betaF1 to which they belong must play an essential role in
      maintaining the 3-dimensional structure of S.pombe PCNA.

PMID- 9592144
TI  - Identification of a gene involved in the generation of 4-thiouridine in tRNA.
AB  - All organisms modify the bases of their RNA after transcription. Relatively
      little is known about the functions that these chemical alterations serve and,
      with very few exceptions, even less has been established regarding the enzymology
      involved. One modified base of known function is 4-thiouridine at position 8 of
      certain bacterial tRNAs, which serves as a photosensor for near-UV light. A gene
      involved in the conversion of uridine at position 8 into 4-thiouridine has been
      identified by genetic screening and its role in 4-thiouridine generation has been
      confirmed biochemically. This same gene, thiI , has recently been shown to play a
      role in thiamin biosynthesis. The purification and characteristics of the
      purified protein are also reported.

PMID- 9592145
TI  - The (6-4) photoproduct of thymine-thymine induces targeted substitution mutations
      in mammalian cells.
AB  - Two major ultraviolet-induced photolesions of TpT, a (6-4) photoproduct [T(6-4)T]
      and a cis-syn cyclobutane TT dimer (T=T), were incorporated into a predetermined
      site of one of the leading and lagging template strands of a double-stranded
      vector, and the modified DNAs were transfected into simian COS-7 cells. The DNAs
      replicated in the cells were recovered and were transfected again into
      Escherichia coli. The DNA replication efficiencies of plasmids containing T(6-4)T
      and T=T in the template strand for lagging strand synthesis were 93 and 79%,
      respectively, as compared with the unmodified DNA. Similar inhibitory effects
      were observed in the cases of the photoproducts in the template strand for
      leading strand synthesis (71 and 58%, respectively). These results indicated that
      T(6-4)T blocked DNA replication more weakly than T=T during leading and lagging
      strand syntheses in mammalian cells. The mutation frequencies of T(6-4)T were 2.3
      and 4.7% in the leading and lagging template strands, respectively. The T=T
      lesion was less mutagenic and induced mutations with 0.2-0.7% frequencies. The
      T(6-4)T lesion primarily elicited 3'-T-->C substitutions, and T=T induced various
      types of mutations. These results indicate that T(6-4)T is more mutagenic than
      T=T during leading and lagging strand syntheses in simian cells. Moreover, this
      is the first evidence that shows T(6-4)T mainly elicits targeted substitutions at
      its 3'-T site in mammalian cells.

PMID- 9592146
TI  - Simple, efficient protocol for enzymatic synthesis of uniformly 13C, 15N-labeled
      DNA for heteronuclear NMR studies.
AB  - The use of uniformly 13C,15N-labeled RNA has greatly facilitated structural
      studies of RNA oligonucleotides by NMR. Application of similar methodologies for
      the study of DNA has been limited, primarily due to the lack of adequate methods
      for sample preparation. Methods for both chemical and enzymatic synthesis of DNA
      oligonucleotides uniformly labeled with 13C and/or 15N have been published, but
      have not yet been widely used. We have developed a modified procedure for
      preparing uniformly 13C,15N-labeled DNA based on enzymatic synthesis using Taq
      DNA polymerase. The highly efficient protocol results in quantitative
      polymerization of the template and approximately 80% incorporation of the labeled
      dNTPs. Procedures for avoiding non-templated addition of nucleotides or for their
      removal are given. The method has been used to synthesize several DNA
      oligonucleotides, including two complementary 15 base strands, a 32 base DNA
      oligonucleotide that folds to form an intramolecular triplex and a 12 base
      oligonucleotide that dimerizes and folds to form a quadruplex. Heteronuclear NMR
      spectra of the samples illustrate the quality of the labeled DNA obtained by
      these procedures.

PMID- 9592147
TI  - Activities of the Sex-lethal protein in RNA binding and protein:protein
      interactions.
AB  - The Drosophila sex determination gene Sex-lethal (Sxl) controls its own
      expression, and the expression of downstream target genes such as transformer ,
      by regulating pre-mRNA splicing and mRNA translation. Sxl codes an RNA-binding
      protein that consists of an N-terminus of approximately 100 amino acids, two 90
      amino acid RRM domains, R1 and R2, and an 80 amino acid C-terminus. In the
      studies reported here we have examined the functional properties of the different
      Sxl protein domains in RNA binding and in protein:protein interactions. The two
      RRM domains are responsible for RNA binding. Specificity in the recognition of
      target RNAs requires both RRM domains, and proteins which consist of the single
      domains or duplicated domains have anomalous RNA recognition properties.
      Moreover, the length of the linker between domains can affect RNA recognition
      properties. Our results indicate that the two RRM domains mediate Sxl:Sxl protein
      interactions, and that these interactions probably occur both in cis and trans.
      We speculate that cis interactions between R1 and R2 play a role in RNA
      recognition by the Sxl protein, while trans interactions stabilize complex
      formation on target RNAs that contain two or more closely spaced binding sites.
      Finally, we show that the interaction of Sxl with the snRNP protein Snf is
      mediated by the R1 RRM domain.

PMID- 9592148
TI  - Characterization of a DEAD box ATPase/RNA helicase protein of Arabidopsis
      thaliana.
AB  - We have isolated cDNAs encoding a novel member of the DEAD box RNA helicase
      family from Arabidopsis. The protein, named AtDRH1, is composed of 619 amino
      acids and the central portion has high similarity with the helicase core region
      of a prototypic RNA helicase, the human nuclear protein p68. The N- and C
      terminal regions are considerably diverged from the animal and yeast p68 homologs
      at the amino acid sequence level, but like the p68 subfamily members, an RGG box
      like domain is present near the C-terminus. RNA blot analysis showed that the
      AtDRH1 transcript accumulates at a high level and almost equally in every part of
      the Arabidopsis plant. The purified, recombinant AtDRH1 was capable of unwinding
      double-stranded RNA in the presence of ATP or dATP and of hydrolyzing ATP. The
      ATPase activity was stimulated by some single-stranded RNAs and DNAs, including
      poly(A) and poly(dT), but not by poly(dA). The ability of the polynucleotides to
      stimulate the ATPase activity was largely consistent with their affinity for
      AtDRH1. These results show that AtDRH1 is a novel type of ATP/dATP-dependent RNA
      helicase and polynucleotide-dependent ATPase.

PMID- 9592149
TI  - DNA repair defect in poly(ADP-ribose) polymerase-deficient cell lines.
AB  - To investigate the physiological function of poly(ADP-ribose) polymerase (PARP),
      we used a gene targeting strategy to generate mice lacking a functional PARP
      gene. These PARP -/- mice were exquisitely sensitive to the monofunctional
      alkylating agent N -methyl- N -nitrosourea (MNU) and gamma-irradiation. In this
      report, we have analysed the cause of this increased lethality using primary
      and/or spontaneously immortalized mouse embryonic fibroblasts (MEFs) derived from
      PARP -/- mice. We found that the lack of PARP renders cells significantly more
      sensitive to methylmethanesulfonate (MMS), causing cell growth retardation, G2/M
      accumulation and chromosome instability. An important delay in DNA strand-break
      resealing was observed following treatment with MMS. This severe DNA repair
      defect appears to be the primary cause for the observed cytoxicity of
      monofunctional-alkylating agents, leading to cell death occurring after G2/M
      arrest. Cell viability following MMS treatment could be fully restored after
      transient expression of the PARP gene. Altogether, these results unequivocally
      demonstrate that PARP is required for efficient base excision repair in vivo and
      strengthens the role of PARP as a survival factor following genotoxic stress.

PMID- 9592150
TI  - Novel internucleotide 3'-NH-P(CH3)(O)-O-5' linkage. Oligo(deoxyribonucleoside
      methanephosphonamidates); synthesis, structure and hybridization properties.
AB  - Diastereomeric dithymidine methanephosphonamidates (TnpmT) were synthesized by
      reaction of 3'-amino-3'-deoxythymidine with 3'- O -acetylthymidin-5-yl
      methanephosphonochloridate. Separated dinucleotide TnpmT(fast) and TnpmT(slow)
      diastereomers were used as building blocks to prepare chimeric dodecathy
      midylates, possessing one to four modified linkages, by means of phosphoramidite
      automated solid phase synthesis. As expected, the methanephosphonamidate
      internucleotide linkage is resistant to nuclease P1, snake venom PDE and 3'
      exonuclease from human plasma. Degradation of dodecathymidylates possessing
      modified internucleotide linkages in alternate positions proved the 'hopping'
      properties of 3'-exonuclease. Oligo(deoxyribonucleotide methanephosphonamidates)
      were tested for their binding affinity to complementary oligomers in thermal
      denaturation experiments. All the oligomers showed lower binding affinity to DNA
      and RNA targets, however, oligomers originating from the TnpmT(fast) dimeric unit
      exhibited better hybridization properties than their diastereomeric TnpmT(slow)
      counterparts. A lowering of T m of approximately 2.4 degrees C (1.0-1.8 degrees
      C) was observed for each introduced TnpmT(fast) modification and 6.0 degrees C
      (4.2-5.0 degrees C) for each TnpmT(slow) modification in duplexes of modified
      dodecathymidylates with dA12(A12) oligomers. The oligo(deoxyribonucleoside
      methanephosphonamidate) designated F4, possessing four modified
      methanephosphonate linkages originating from the TnpmT(fast) diastereomeric unit,
      exhibits a tendency for triplex formation, as was demonstrated in thermal
      denaturation experiments with the d(A21C4T21) hairpin oligomer.

PMID- 9592151
TI  - DNA-methyltransferase SsoII interaction with own promoter region binding site.
AB  - The investigation of Sso II DNA-methyltransferase (M.Sso II) interaction with the
      intergenic region of Sso II restriction-modification system was carried out.
      Seven guanine residues protected by M. Sso II from methylation with
      dimethylsulfate and thus probably involved in enzyme-DNA recognition were
      identified. Six of them are located symmetrically within the 15 bp inverted
      repeat inside the Sso II promoter region. The crosslinking of Sso II
      methyltransferase with DNA duplexes containing 5-bromo-2'-deoxyuridine (br5dU)
      instead of thymidine was performed. The crosslinked products were obtained in all
      cases, thus proving that tested thymines were in proximity with enzyme. The
      ability to produce the crosslinked products in one case was 2-5-fold higher than
      in other ones. This allowed us to imply that thymine residue in this position of
      the inverted repeat could be in contact with M. Sso II. Based on the experimental
      data, two symmetrical 4 bp clusters (GGAC), which could be involved in the
      interaction with M. Sso II in the DNA-protein complex, were identified. The model
      of M. Sso II interaction with its own promoter region was proposed.

PMID- 9592152
TI  - Triple helices containing arabinonucleotides in the third (Hoogsteen) strand:
      effects of inverted stereochemistry at the 2'-position of the sugar moiety.
AB  - Arabinonucleic acid, the 2'-stereoisomer of RNA, was tested for its ability to
      recognize double-helical DNA, double-helical RNA and RNA-DNA hybrids. A
      pyrimidine oligoarabinonucleotide (ANA) was shown to form triple-helical
      complexes only with duplex DNA and hybrid DNA (Pu):RNA (Py) with an affinity that
      was slightly lower relative to the corresponding pyrimidine oligodeoxynucleotide
      (DNA) third strand. Neither the ANA nor DNA third strands were able to bind to
      duplex RNA or hybrid RNA (Pu):DNA (Py). In contrast, an RNA third strand
      recognized all four possible duplexes (DD, DR, RD and RR), as previously
      demonstrated. Such an understanding can be applied to the design of sequence
      selective oligonucleotides which interact with double-stranded nucleic acids and
      emphasizes the role of the 2'-OH group as a general recognition and binding
      determinant of RNA.

PMID- 9592153
TI  - GAGA factor binding to DNA via a single trinucleotide sequence element.
AB  - GAGA transcription factor (GAF) is an essential protein in Drosophila , important
      for the transcriptional regulation of numerous genes. GAF binds to GA repeats in
      the promoters of these genes via a DNA-binding domain containing a single zinc
      finger. While GAF binding sites are typically composed of 3.5 GA repeats, the
      Drosophila hsp70 gene contains much smaller elements, some of which are as little
      as three bases (GAG) in length. Interestingly, the binding of GAF to more distant
      trinucleotide elements is relatively strong and not appreciably affected by the
      removal of larger GA arrays in the promoter. Moreover, a simple synthetic GAG
      sequence is sufficient to bind GAF in vitro . Here we directly compare the
      affinity of GAF for different sequence elements by immunoprecipitation and gel
      mobility shift analysis. Furthermore, our measures of the concentration of GAF in
      vivo indicate that it is a highly abundant nuclear protein, prevalent enough to
      occupy a sizable fraction of correspondingly abundant trinucleotide sites.

PMID- 9592154
TI  - Conformational properties of DNA dodecamers containing four tandem repeats of the
      CNG triplets.
AB  - We studied DNA dodecamers (CAG)4, (CCG)4, (CGG)4 and (CTG)4by CD spectroscopy and
      polyacrylamide gel electrophoresis. Each dodecamer adopted several ordered
      conformers which denatured in a cooperative way. Stability of the conformers
      depended on the dodecamer concentration, ionic strength, temperature and pH. The
      dodecamers, having a pyrimidine base in the triplet center, generated foldbacks
      at low ionic strength whose stem conformations were governed by the GC pairs. At
      high salt, (CCG)4 isomerized into a peculiar association of two strands. The
      association was also promoted by high oligonucleotide concentrations. No similar
      behavior was exhibited by (CTG)4. At low salt, (CGG)4 coexisted in two
      bimolecular conformers whose populations were strongly dependent on the ionic
      strength. In addition, (CGG)4 associated into a tetraplex at acidic pH. A
      tetraplex was even observed at neutral pH if the (CGG)4 concentration was
      sufficiently high. (CAG)4 was very stable in a monomolecular conformer similar to
      the known extremely stable foldback of the (GCGAAGC) heptamer. Nevertheless, even
      this very stable conformer disappeared if (CTG)4 was added to the solution of
      (CAG)4. Association of the complementary strands was also strongly preferred to
      the particular strand conformations by the other couple, (CCG)4 and (CGG)4.

PMID- 9592155
TI  - Characterisation of Bacillus stearothermophilus PcrA helicase: evidence against
      an active rolling mechanism.
AB  - PcrA from Bacillus stearothermophilus is a DNA helicase for which, despite the
      availability of a crystal structure, there is very little biochemical
      information. We show that the enzyme has a broad nucleotide specificity, even
      being able to hydrolyse ethenonucleotides, and is able to couple the hydrolysis
      to unwinding of DNA substrates. In common with the Escherichia coli helicases Rep
      and UvrD, PcrA is a 3'-5' helicase but at high protein concentrations it can also
      displace a substrate with a 5' tail. However, in contrast to Rep and UvrD, we do
      not see any evidence for dimerisation of the protein even in the presence of DNA.
      The enzyme shows a specificity for the DNA substrate in gel mobility assays, with
      the preferred substrate being one with both single and double stranded regions of
      DNA. We propose that these data, together with existing structural evidence,
      support an inchworm rather than a rolling model for 3'-5' helicase activity.

PMID- 9592156
TI  - Thermodynamics of internal C.T mismatches in DNA.
AB  - Thermodynamics of 23 oligonucleotides with internal single C.T mismatches were
      obtained by measuring UV absorbance as a function of temperature. Results from
      these 23 duplexes were combined with three measurements from the literature to
      derive nearest-neighbor thermodynamic parameters for seven linearly independent
      trimer sequences with internal C.T mismatches. The data show that the nearest
      neighbor model is adequate for predicting thermodynamics of oligonucleotides with
      internal C.T with average deviations for Delta G degrees37, Delta H degrees,
      Delta S degrees and T m of 6.4%, 9.9%, 10.6%, and 1.9 degreesC respectively. C.T
      mismatches destabilize the duplex in all sequence contexts. The thermodynamic
      contribution of C. T mismatches to duplex stability varies weakly depending on
      the orientation of the mismatch and its context and ranges from +1.02 kcal/mol
      for GCG/CTC and CCG/GTC to +1.95 kcal/mol for TCC/ATG.

PMID- 9592157
TI  - DNA binding and transcription activation specificity of hepatocyte nuclear factor
      4.
AB  - Hepatocyte nuclear factor 4 (HNF-4) is an orphan intracellular receptor that
      appears to be a key factor in the regulation of energy metabolism. In order to
      gain greater understanding of the binding and activation requirements of HNF-4,
      we performed genetic analysis of the apoCIII promoter, a promoter that has
      previously been shown to be highly sensitive to HNF-4-induced transcription. We
      identified two elements within the apoCIII promoter that bind HNF-4, either of
      which are sufficient to confer promoter induction in response to HNF-4. These two
      elements are both direct repeat-like in nature, but they differ significantly in
      motif sequence and the repeats are separated by either 1 or 2 nt. Therefore, to
      better define the DNA sequence recognition requirements of HNF-4, we utilized PCR
      based binding site selection. HNF-4 selected for direct repeat-like elements with
      either 1 or 2 nt between the repeats. Surprisingly, the strongest selection was
      for a core motif that included the nucleotides between the repeats. Mutation of
      the nucleotide between the repeats resulted in a 6-fold reduction in affinity,
      indicating that the interaction between HNF-4 and the intervening nucleotide(s)
      is critical for high affinity binding.

PMID- 9592158
TI  - Plant cytosolic tRNAHis possesses an exceptional C54 in the canonical TPsiC loop.
AB  - A nuclear gene coding for tRNAHis from Arabidopsis has been reported to contain
      C54in the TPsiC loop, although the corresponding nucleotide is an invariant U or
      a derivative in nearly all other tRNAs. The only previously reported plant
      cytosolic tRNAHis sequence, from lupin, has U54. To re-examine plant cytosolic
      tRNAsHis and their genes we have used DNA and RNA sequence analyses, restriction
      enzyme digestion of PCR-amplified tRNA genes, RNA hybridization and in vivo
      aminoacylation assays. Our results suggest that Arabidopsis nuclear tRNAHis genes
      ubiquitously contain C54, as do those from tobacco, lupin and pea. The C54
      nucleotide is maintained in the mature tRNAHis, which is aminoacylated in vivo ,
      but to a relatively low level compared with other tRNAs examined. Finally, it was
      shown that an Arabidopsis tRNAHis gene with T54in place of C54 is over 5-fold
      more transcriptionally active than the wild-type gene using an in vitro system
      derived from plant nuclei. A possible role for this apparently sub-optimal
      tRNAHis sequence is suggested.

PMID- 9592160
TI  - Mg2+ binding and structural stability of mature and in vitro synthesized
      unmodified Escherichia coli tRNAPhe.
AB  - Mature tRNAPhe from Escherichia coli and the transcript of its gene lacking
      modified nucleotides were compared by a variety of physical techniques. Melting
      experiments revealed that at a low Mg2+level the transcript was partially
      denatured, while the mature tRNA possessed intact tertiary interactions.
      Mg2+binding to both tRNAs was studied by CD and UV techniques as well as by using
      the Mg2+-sensitive fluorescence indicator, 8-hydroxyquinoline 5-sulfonic acid.
      Both tRNA forms exhibited a single strong Mg2+-binding site, its dissociation
      constant was 10-fold higher for the transcript. Conformational changes in
      response to Mg2+ addition measured by CD and UV spectrometry revealed no
      difference for the estimated binding cooperativity and strong differences for
      affinities of Mg2+-binding sites for the two tRNA forms. Conformational
      transitions in mature and in in vitro synthesized tRNA required the binding of
      two Mg2+ ions per molecule and therefore should be associated not only with a
      single strong binding site. The Mg2+ dependence of Stokes radii measured by gel
      filtration revealed insignificant differences between the overall sizes of the
      two tRNA forms at physiological Mg2+ levels (>1 mM). Taken together, these
      results suggest that modified nucleotides stabilize tertiary interactions and
      increase the structure stability without affecting the mechanism of Mg2+binding
      and overall folding of the tRNA molecule. This conclusion is supported by the
      known biological activity of the E. coli tRNAPhe gene transcript.

PMID- 9592159
TI  - Selection and characterization of RNAs that relieve transcriptional interference
      in Escherichia coli.
AB  - Oligonucleotide-directed triple helix formation offers a method for duplex DNA
      recognition, and has been proposed as an approach to the rational design of gene
      specific repressors. Indeed, certain RNA and DNA oligonucleotides have previously
      been shown to bind duplex DNA and repress in vitro transcription by occluding the
      binding of transcription factors or RNA polymerase at target genes. While similar
      oligonucleotides have reportedly caused repression of target genes in cultured
      cells, physical evidence of triple helix formation in vivo is generally lacking.
      In the present study we wished to determine whether RNA transcripts could repress
      the activity of an Escherichia coli promoter in vivo by binding to the duplex
      promoter DNA. An in vivo genetic selection previously developed to identify DNA
      binding proteins was modified for this purpose. Using expression libraries
      encoding RNAs predisposed to forming triple helices with a DNA target site, we
      have selected RNA transcripts that confer survival to E.coli by disrupting
      transcriptional interference. Surprisingly, genetic and biochemical evidence
      shows that these RNAs do not form triple helices at the target promoter in vivo ,
      despite the fact that they contain sequences capable of forming triple helices at
      the duplex DNA target in vitro . Rather, the selected RNAs appear to disrupt
      transcriptional interference via an antisense mechanism.

PMID- 9592161
TI  - Site-specific integration of Agrobacterium T-DNA in Arabidopsis thaliana mediated
      by Cre recombinase.
AB  - In this study Agrobacterium tumefaciens transferred DNA (T-DNA) was targeted to a
      chromosomally introduced lox site in Arabidopsis thaliana by employing the Cre
      recombinase system. To this end, Arabidopsis target lines were constructed which
      harboured an active chimeric promoter-lox-cre gene stably integrated in the plant
      genome. A T-DNA vector with a promoterless lox -neomycin phosphotransferase
      (nptII) fusion was targeted to this genomic lox site with an efficiency of 1.2
      2.3% of the number of random events. Cre-catalyzed site-specific recombination
      resulted in restoration of nptII expression by translational fusion of the lox
      nptII sequence in the integration vector with the transcription and translation
      initiation sequences present at the target site, allowing selective enrichment on
      medium containing kanamycin. Simultaneously, the coding sequence of the Cre
      recombinase was disconnected from these same transcription and translation
      initiation signals by displacement, aimed at preventing the efficient reversible
      excision reaction. Of the site-specific recombinants, 89% were the result of
      precise integration. Furthermore, approximately 50% of these integrants were
      single copy transformants, based on PCR analysis. Agrobacterium T-DNA, which is
      transferred to plant cells as a single-stranded linear DNA structure, is in
      principle incompatible with Cre-mediated integration. Nevertheless, the results
      presented here clearly demonstrate the feasibility of the Agrobacterium -mediated
      transformation system, which is generally used for transformation of plants, to
      obtain site-specific integration.

PMID- 9592162
TI  - Inhibition of PNA triplex formation by N4-benzoylated cytosine.
AB  - The synthesis of N-((N4-(benzoyl)cytosine-1-yl)acetyl)- N -(2-Boc
      aminoethyl)glycine (CBz) and the incorporation of this monomer into PNA oligomers
      are described. A single CBzresidue within a 10mer homopyrimidine PNA is capable
      of switching the preferred binding mode from a parallel to an antiparallel
      orientation when targeting a deoxyribonucleotide sequence at neutral pH. The
      resulting complex has a thermal stability equal to that of the corresponding PNA
      DNA duplex, indicative of a strong destabilization of Hoogsteen strand PNA
      binding due to steric interference by the benzoyl moieties. Accordingly,
      incorporation of the CBz residue into linked PNAs (bis-PNAs) results in greatly
      reduced thermal stability of the formed PNA:DNA complexes. Thus, incorporation of
      the CBz monomer could eliminate the stability bias of triplex-forming sequences
      in PNA used in hybridization arrays and combinatorial library formats.
      Furthermore, it is shown that the benzoyl moiety does not severely interfere with
      Watson-Crick hydrogen bonding, thereby presenting an interesting route for novel
      cytosine modifications.

PMID- 9592163
TI  - Computational approaches to identify leucine zippers.
AB  - The leucine zipper is a dimerization domain occurring mostly in regulatory and
      thus in many oncogenic proteins. The leucine repeat in the sequence has been
      traditionally used for identification, however with poor reliability. The coiled
      coil structure of a leucine zipper is required for dimerization and can be
      predicted with reasonable accuracy by existing algorithms. We exploit this fact
      for identification of leucine zippers from sequence alone. We present a program,
      2ZIP, which combines a standard coiled coil prediction algorithm with an
      approximate search for the characteristic leucine repeat. No further information
      from homologues is required for prediction. This approach improves significantly
      over existing methods, especially in that the coiled coil prediction turns out to
      be highly informative and avoids large numbers of false positives. Many problems
      in predicting zippers or assessing prediction results stem from wrong sequence
      annotations in the database.

PMID- 9592165
TI  - Multiple rounds of transcription by RNA polymerase II at covalently cross-linked
      templates.
AB  - An important control point for gene regulation is the frequency of initiations
      leading to different numbers of RNA polymerases simultaneously transcribing the
      same gene. To date, the only direct assay for multiple-round transcription by RNA
      polymerase II in vitro required G-free cassette-containing templates and GTP-free
      conditions and was thus restricted in application. Here we used instead templates
      containing a triplex-directed interstrand psoralen-DNA cross-link to block RNA
      polymerase II elongation at a specific location. Covalently cross-linked
      templates allowed simultaneous detection of both specific initiation and
      reinitiation with any combination of promoter and transcribed sequence. In
      reconstituted systems, identical stacking of RNA polymerases was observed when
      the first polymerase was halted by GTP deprivation at the end of a G-free
      cassette or by a covalent cross-link downstream of different transcribed
      sequences. In contrast to transcription of G-free cassettes, reinitiation was
      unaffected by the transcription factor SII on sequences containing all four
      nucleotides. In crude nuclear extracts, transcription of covalently cross-linked
      templates yielded a reinitiation pattern with a wider spacing than in more
      purified fractions, indicating that the elongation complexes from nuclear extract
      contained a different form of RNA polymerase II or a different complement of
      associated factors.

PMID- 9592164
TI  - Sequence and expression characteristics of a nuclear-encoded chloroplast sigma
      factor from mustard (Sinapis alba).
AB  - Plant chloroplasts contain transcription factors that functionally resemble
      bacterial sigma factors. We have cloned the full-length cDNA from mustard
      (Sinapis alba) for a 53 kDa derived polypeptide that contains similarity to
      regions 1.2-4.2 of sigma70-type factors. The amino acid sequence at the N
      terminus has characteristics of a chloroplast transit peptide. An in vitro
      synthesized polypeptide containing this region was shown to be imported into the
      chloroplast and processed. The recombinant factor lacking the N-terminal
      extension was expressed in Escherichia coli and purified. It confers the ability
      on E.coli core RNA polymerase to bind specifically to a DNA fragment that
      contains the chloroplast psbA promoter. Transcription of the psbA template by
      E.coli core enzyme in the presence of recombinant SIG1 results in enhanced
      formation of transcripts of the size expected for correct initiation at the in
      vivo start site. Together, these data suggest that the mature protein acts as one
      of the chloroplast transcription factors in mustard. RNA gel blot hybridization
      reveals a transcript at approximately 1.8 kb, which is more abundant in light
      grown than in dark-grown mustard seedlings.

PMID- 9592166
TI  - Novel salivary gland specific binding elements located in the PSP proximal
      enhancer core.
AB  - The murine parotid secretory protein (PSP) gene is expressed selectively at high
      levels in parotid and sublingual salivary glands. Previously, the transcriptional
      activity of a PSP mini-gene, called Lama, was shown to be dependent on a 1.5 kb
      region located 3 kb upstream of the transcription start site. Here, functional
      studies in transgenic mice demonstrate that this proximal regulatory region has
      properties of a parotid and sublingual gland specific enhancer. Protein-binding
      experiments identify multiple sequence-specific binding complexes spanning the
      entire 1.5 kb enhancer region. Several sequence elements bound specifically by
      parotid and/or sublingual gland nuclear extracts, including consensus binding
      elements for previously described transcription factors as well as novel binding
      elements are located in the proximal enhancer region. A deletion analysis of the
      enhancer region in transgenic mice identified a core sequence of 700 bp. This
      region contains five elements bound specifically by nuclear proteins isolated
      from the PSP-expressing parotid and sublingual glands. Two of these elements,
      denoted parotid gland element I (PGE I) and sublingual gland element I (SLE I),
      are novel salivary gland specific binding elements, bound uniquely by parotid and
      sublingual gland nuclear extracts, respectively.

PMID- 9592168
TI  - Structural features of the minimal DNA binding domain (M98-F219) of human
      nucleotide excision repair protein XPA.
AB  - XPA, an essential protein in nucleotide excision repair (NER), interacts with
      damaged DNA and other proteins (RPA, ERCC1 and TFIIH) to remove a wide variety of
      chemically and structurally distinct DNA lesions from the eukaryotic genome. To
      understand the structural basis for the role of XPA in the repair process, the
      structure of the minimal DNA binding domain of human XPA [XPA-MBD (M98-F219)] was
      studied by NMR spectroscopy. A three-dimensional structure for XPA-MBD was
      generated using distance geometry and simulated annealing methods from NOE-based
      distance restraints, hydrogen bond and Zn-S distance restraints, and dihedral
      restraints. The structure calculations indicate that XPA-MBD contains elements of
      well-defined secondary structure interspaced with disordered loops organized into
      two non-interactive sub-domains: a zinc-binding core (D101-K137) and a loop-rich
      domain (L138-F219). The zinc-associated core contains an antiparallel beta-sheet
      (Y102-C105 and K110-M113) and an alpha-helix (C126-K137) separated by a poorly
      defined turn, reminiscent of the structure of the zinc-binding domain of the
      chicken erythroid transcription factor GATA-1 when bound to its cognate DNA
      sequence. The loop-rich domain contains a triple-strand antiparallel beta-sheet
      (L138-T140, L182-M178 and K163-K167), three loops (K151-L162, N169-D177 and Q208
      F219) and three alpha-helices (K141-L150, K183-W194 and Q197-R207). The XPA-MBD
      structure is discussed in terms of known functions: binding single- and double
      stranded DNA and binding RPA.

PMID- 9592167
TI  - Elements in abasic site recognition by the major human and Escherichia coli
      apurinic/apyrimidinic endonucleases.
AB  - Sites of base loss in DNA arise spontaneously, are induced by damaging agents or
      are generated by DNA glycosylases. Repair of these potentially mutagenic or
      lethal lesions is carried out by apurinic/apyrimidinic (AP) endonucleases. To
      test current models of AP site recognition, we examined the effects of site
      specific DNA structural modifications and an F266A mutation on incision and
      protein-DNA complex formation by the major human AP endonuclease, Ape. Changing
      the ring component of the abasic site from a neutral tetrahydrofuran (F) to a
      positively charged pyrrolidine had only a 4-fold effect on the binding capacity
      of Ape. A non-polar 4-methylindole base analog opposite F had a <2-fold effect on
      the incision activity of Ape and the human protein was unable to incise or
      specifically bind 'bulged' DNA substrates. Mutant Ape F266A protein complexed
      with F-containing DNA with only a 6-fold reduced affinity relative to wild-type
      protein. Similar studies are described using Escherichia coli AP endonucleases,
      exonuclease III and endonuclease IV. The results, in combination with previous
      findings, indicate that the ring structure of an AP site, the base opposite an AP
      site, the conformation of AP-DNA prior to protein binding and the F266 residue of
      Ape are not critical elements in targeted recognition by AP endonucleases.

PMID- 9592170
TI  - The influence of fluorescent dye structure on the electrophoretic mobility of end
      labeled DNA.
AB  - Over the past 10 years, fluorescent end-labeling of DNA fragments has evolved
      into the preferred method of DNA detection for a wide variety of applications,
      including DNA sequencing and PCR fragment analysis. One of the advantages
      inherent in fluorescent detection methods is the ability to perform multi-color
      analyses. Unfortunately, labeling DNA fragments with different fluorescent tags
      generally induces disparate relative electrophoretic mobilities for the
      fragments. Mobility-shift corrections must therefore be applied to the
      electrophoretic data to compensate for these effects. These corrections may lead
      to increased errors in the estimation of DNA fragment sizes and reduced
      confidence in DNA sequence information. Here, we present a systematic study of
      the relationship between dye structure and the resultant electrophoretic mobility
      of end-labeled DNA fragments. We have used a cyanine dye family as a paradigm and
      high-resolution capillary array electrophoresis (CAE) as the instrumentation
      platform. Our goals are to develop a general understanding of the effects of dyes
      on DNA electrophoretic mobility and to synthesize a family of DNA end-labels that
      impart identically matched mobility influences on DNA fragments. Such matched
      sets could be used in DNA sequencing and fragment sizing applications on
      capillary electrophoresis instrumentation.

PMID- 9592169
TI  - Quantitative analysis of in vivo ribosomal events at UGA and UAG stop codons.
AB  - An in vivo translation assay system has been designed to measure, in one and the
      same assay, the three alternatives for a ribosome poised at a stop codon
      (termination, read-through and frameshift). A quantitative analysis of the
      competition has been done in the presence and absence of release factor (RF)
      mutants, nonsense suppressors and an upstream Shine-Dalgarno-like sequence. The
      ribosomal +1 frameshift product is measurable when the stop codon is decoded by
      wild-type or mutant RF (prf A1 or prf B2) and also in the presence of competing
      suppressor tRNAs. Frameshift frequency appears to be influenced by RF activity.
      The amount of frameshift product decreases in the presence of competing
      suppressor tRNAs, however, this decrease is not in proportion to the
      corresponding increase in the suppression product. Instead, there is an increase
      in the total amount of protein expressed from the gene, perhaps due to the
      purging of queued ribosomes. Mutated RFs reduce the total output of the reporter
      gene by reducing the amount of all three protein products. The nascent peptide
      has earlier been shown to influence the translation termination process by
      interacting with the RFs. At 42 degrees C in a temperature-sensitive RF mutant
      strain, protein measurements indicate that the nascent peptide seems to influence
      the binding efficiencies of the RFs.

PMID- 9592171
TI  - Characterization of the RNA binding proteins forming complexes with a novel
      putative regulatory region in the 3'-UTR of TNF-alpha mRNA.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine regulator of an early
      immune response and the central mediator of deleterious effects of systemic
      inflammatory response syndrome. High production of TNF-alpha by macrophages
      requires two signals: the first signal induces transcription, while the second
      signal releases the translational repression of TNF-alpha mRNA. The translational
      control of TNF-alpha expression is conferred by sequences in the 3'-untranslated
      region (3'-UTR) of its mRNA. Previously, we have characterized protein complexes
      binding to the main AU-rich region in the 3'-UTR of murine TNF-alpha mRNA. Here
      we describe a second protein binding region which is located 147 bases downstream
      of the first region and interacts with at least seven distinct protein species
      present in murine macrophages. The second protein binding motif contains a single
      AUAUUUAU sequence motif; a mutation of this sequence to AUAGGUAU abrogates the
      binding of proteins. Some of the macrophage proteins mutually compete for the
      binding to both regions, while others seem to be region specific. The existence
      of the two protein binding domains explains the previously published data
      addressing the translatibility of a reporter gene linked to various deletion
      mutants of the TNF-alpha 3'-UTR. Both the sequence and position of the two
      putative protein binding regions are highly conserved across species, indicating
      their important role in the regulation of translational repression and
      inducibility of TNF-alpha synthesis.

PMID- 9592173
TI  - A high-throughput hybridization method for titer determination of viruses and
      gene therapy vectors.
AB  - One of the challenges facing researchers working with viruses and gene therapy
      vectors is the need to rapidly assay for infectious virus. Current methods used
      to titer many viruses are cumbersome and are not amenable to handling large
      numbers of samples. Here we describe the development of an assay that can rapidly
      quantify infectious viruses and gene therapy vectors. The assay relies on
      biological amplification of viral sequences and hybridization of labeled probes
      to immobilized nucleic acid from infected cells. The amplification of the viral
      genome makes this a highly sensitive method. The assay is configured in a high
      throughput format that has been used to detect recombinant adeno-associated virus
      (AAV), wild-type AAV and infectious adenovirus. The assay is quantitative, and
      can be used to titer virus preparations with or without a known standard.

PMID- 9592172
TI  - Multiple domains for initiator binding proteins TFII-I and YY-1 are present in
      the initiator and upstream regions of the rat XDH/XO TATA-less promoter.
AB  - We previously reported that the TATA-less rat xanthine dehydrogenase/oxidase
      (XDH/XO) promoter is organized with multiple initiator elements (Inr 1, 2, 3 and
      4). Additionally, we identified six factor binding footprints in the upstream
      region of this promoter (FP 1-FP 6), two of which (FP 2 and FP 4) we showed to be
      C/EBP binding sites. In this report we continue our characterization of the
      XDH/XO promoter, detailing other cis elements which comprise the Inr and upstream
      binding factors. Interestingly, multiple binding domains for known initiator
      binding proteins, YY-1 and USF-related factor/TFII-I, have been identified which
      potentially play an important role in transcription initiation.

PMID- 9592174
TI  - Octamer-primed cycle sequencing using dye-terminator chemistry.
AB  - Octamer Sequencing Technology, OST, is a method of DNA sequencing using single
      octamer oligonucleotides to prime cycle sequencing reactions. This sequencing
      strategy is faster than a traditional primer-walking strategy, since access to
      this optimized octamer library eliminates delays associated with designing and
      synthesizing gene specific primers. In this report, OST has been optimized for
      fluorescent, dye-terminator cycle sequencing reactions to facilitate parallel
      processing of samples. The successful adaptation of OST to an automated
      sequencing platform and the design of and access to an octamer library are
      critical steps towards developing an efficient 'closed-loop' DNA sequencing
      system.

PMID- 9592175
TI  - MALDI-TOF mass spectrometric typing of single nucleotide polymorphisms with mass
      tagged ddNTPs.
AB  - A matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      based method has recently been reported for the typing of single nucleotide
      polymorphisms using single nucleotide primer extension. This method is limited in
      some cases by the resolution of the mass determination, as the mass difference
      between nucleotides can be as little as 9 Da (the difference between A and T). A
      variation of this method is described here in which a mass-tagged
      dideoxynucleotide is employed in the primer extension reactions in place of the
      unmodified dideoxynucleotide. The increased mass difference due to the presence
      of the mass-tags substantially improves the accuracy and versatility of the
      procedure.

PMID- 9592176
TI  - An alternative PCR assay for quantifying mitochondrial DNA in crude preparations.
AB  - A method is described for the quantification of mitochondrial DNA present in
      crude biological preparations. A known copy number of a standard is amplified in
      the presence of inactivated target DNA so as to determine the overall efficiency
      of the PCR process in a particular sample. In this way any inhibitory and/or
      stimulatory substances present in sample preparations can be taken into account.
      To reduce tube-to-tube variations product DNA quantification is limited to small
      cycle numbers. Using this method quantitations of DNA amounts in different crude
      preparations can be compared.

PMID- 9592177
TI  - A novel dosage approach for evaluation of SMANCS [poly-(styrene-co-maleyl-half-n
      butylate) - neocarzinostatin] in the treatment of primary hepatocellular
      carcinoma.
AB  - We report a Phase I/II clinical trial of poly-(styrene-co-maleyl-half-n-butylate)
      neocarzinostatin (SMANCS) for intra-arterial treatment of hepatoma. Early
      patients received 4 or 8 mg SMANCS dissolved in Lipiodol; later patients were
      treated according to tumour size and degree of filling achieved. SMANCS/Lipiodol
      drained rapidly from normal liver but was retained within tumour interstitium.
      Tumour nodules filled with SMANCS/Lipiodol usually stabilised and often
      regressed. No UICC criteria-defined responses were achieved, partly due to
      difficulties of filling several lesions simultaneously. Signs of therapeutic
      activity suggest a more extensive clinical study is warranted.

PMID- 9592178
TI  - Increased expression of estrogen receptor beta in chemically transformed human
      breast epithelial cells.
AB  - Recent molecular cloning of estrogen receptor beta (ERbeta) suggests alternative
      pathways of estrogen signaling, but little is known concerning the role of ERbeta
      in the development of human breast cancer. In the present study, expression of
      ERalpha and ERbeta mRNA was determined in a series of chemically transformed
      human breast epithelial cells as well as various normal and malignant breast
      cancer cell lines. We observed a very low level of ERbeta expression in the
      mortal S130 and the spontaneously immortalized MCF10-F human breast epithelial
      cell lines. As MCF-10F cells were treated with environmental chemical
      carcinogens, an elevated level of ERbeta expression was observed in the resultant
      transformed BP1, D3 and BP1-ras cells. An even higher level of ERbeta expression
      was detected in the more transformed BP1-E, D3-1 and D3-1-ras cell lines.
      Therefore, results from our study indicate that expression of ERbeta can be
      induced in chemical carcinogen-transformed human breast epithelial cells, and the
      more transformed cells showed higher levels of ERbeta expression, regardless of
      which chemical carcinogens were initially used for cell transformation. These
      results suggest that expression of ERbeta may contribute to the initiation and
      progression of chemical carcinogen-induced neoplastic transformation.

PMID- 9592180
TI  - The NGFI-B subfamily of the nuclear receptor superfamily (review).
AB  - NGFI-B, Nurr1 and NOR-1 have structural features of ligand-activated
      transcriptional regulators and constitute the NGFI-B subfamily within the nuclear
      receptor superfamily. Since specific ligands for these molecules have not yet
      been identified, they are often called orphan nuclear receptors. Genes of the
      NGFI-B subfamily are classified as immediate-early genes that are induced rapidly
      but transiently by a variety of stimuli. Evidence accumulated over the past
      decade suggests this subfamily is involved in important physiological processes
      and cancer development. In this communication, we summarize and discuss their
      structural features, gene expression, physiological roles and oncological
      significance.

PMID- 9592179
TI  - Tumor regression in mice following vaccination with human papillomavirus E7
      recombinant protein in PROVAX.
AB  - Induction of CD8+ cytotoxic T lymphocytes (CTLs) specific for human
      papillomavirus (HPV) antigens provides an attractive strategy for immunotherapy
      of HPV-related cancers in humans. In this study, we investigated the potential of
      utilizing soluble E7 protein of HPV 16 in an adjuvant formulation, PROVAX as a
      vaccine against a progressively growing E7 transfected K1735-X21 (H-2k)
      metastatic melanoma cells (HOPE2) in a mouse model. Vaccination of HOPE2 tumor
      bearing mice (C3H) with E7 protein in PROVAX resulted in significant inhibition
      of tumor growth, compared to mice vaccinated with E7 in Alum or saline. In vivo
      depletion of CD8+ or CD4+ cells indicated that CD8+ cells are the major effector
      cells in mediating the anti-tumor activity in this model. Furthermore, E7
      specific CTL activity in vitro was detected in tumor bearing mice vaccinated with
      E7-PROVAX. Our studies suggest that recombinant HPV antigens in combination with
      PROVAX could serve as an effective subunit vaccine to stimulate tumor specific
      CD8+ T cell mediated immunity against HPV-related cancers.

PMID- 9592181
TI  - Frequent microsatellite instability and loss of heterozygosity in the region
      including BRCA1 (17q21) in young patients with gastric cancer.
AB  - It is known that nearly 5% of gastric carcinomas arise under the age of 40. To
      elucidate genetic alterations in these patients, we performed studies using
      microsatellite assay in 27 gastric cancers under 35 years of age, composed of 5
      well and 22 poorly differentiated adenocarcinomas. We detected replication errors
      (RERs) in 18 (67%) of 27 tumors, but no germline mutation in DNA mismatch repair
      genes (hMLH1 and hMSH2), except fory 3 somatic mutations in the hMLH1 gene. Loss
      of heterozygosity (LOH) at D17S855, located on chromosome 17q21 (BRCA1), was
      detected in 8 (40%) of 20 informative cases. In 12 (44%) of 27 cases, LOH on
      chromosome 17q12-21 including the BRCA1 was found in several neighboring markers
      in this region, while no mutation was found in the BRCA1 gene. Four (40%) of 10
      scirrhous type gastric cancers exhibited wide allelic deletions on chromosome
      17q12-21. These results overall suggest that young gastric cancer patients
      display highly frequent micro-satellite instability that might be due to defect
      of DNA repair system rather than hMLH1 and hMSH2. In addition, chromosome 17q12
      21 including BRCA1 locus may contain a candidate for tumor suppressor gene,
      particularly in scirrhous type gastric cancers arising in young patients.

PMID- 9592182
TI  - Expression of CD44 containing variant exon 9 (CD44v9) in gastric adenomas and
      adenocarcinomas: relation to the proliferation and progression.
AB  - The expression of CD44 splice variant containing exon 14 (variant exon 9: CD44v9)
      was examined immunohistochemically in non-neoplastic mucosa, adenoma and
      adenocarcinoma of the stomach and analyzed the relation with the expression of Ki
      67 antigen and p53 protein. In non-neoplastic gastric mucosa, basolateral
      membrane of the epithelial cells in the pyloric glands showed the expression of
      CD44v9. The epithelial cells in the intestinal metaplastic mucosa of the stomach
      sometimes expressed CD44v9. In the neoplastic lesions, the expression of CD44v9
      was detected in 20% (34/170) of the adenomas and 28% (132/478) of the
      adenocarcinomas, respectively. The incidence of CD44v9 expression did not differ
      among histological type of gastric carcinoma. Twelve per cent of the
      adenocarcinomas showed strong expression of CD44v9, whereas non of the adenomas
      did. The incidence of CD44v9 expression was significantly higher in carcinomas
      invading into muscularis propria or the cases of stages 3 and 4 in comparison
      with that in carcinomas limited to submucosa or the stages 1 and 2 cases
      (p<0.05). The incidence of positive cases was higher in carcinomas with lymph
      node metastasis than those without metastasis (p<0.05). The expression of CD44v9
      was significantly correlated with the expression of Ki-67 (p<0.05). It was also
      correlated with the expression of p53 protein in the tumor cells (p<0.01). These
      findings overall suggest that the expression of CD44v9 may be associated with the
      development as well as progression of the gastric carcinomas.

PMID- 9592183
TI  - Cytogenetic analysis of de novo acute myeloid leukemia with trilineage
      myelodysplasia in comparison with myelodysplastic syndrome evolving to acute
      myeloid leukemia.
AB  - Characteristics of karyotypes were analyzed in de novo acute myeloid leukemia
      (AML) with trilineage myelodysplasia (AML/TMDS) at initial diagnosis and compared
      with myelodysplastic syndrome (MDS) cases that had evolved to AML (MDS/AML).
      Abnormal karyotypes were seen in 11 of 19 patients with AML/TMDS and 13 of 16
      MDS/AML cases. Trisomy 8 was observed in 3 AML/TMDS cases as a sole anomaly and
      was also present in 3 MDS/AML cases but not as a sole finding. Although MDS/AML
      frequently displayed monosomies or long-arm deletions of chromosome 5, 7 and 9,
      only one case exhibited long-arm deletion (of chromosome 7) in AML/TMDS. Two or
      more chromosome aberrations were found in some cases in both groups. These
      findings suggest that AML/TMDS had passed through several preleukemic stages at
      diagnosis, as has been well documented in MDS and MDS/AML. Additionally, clonal
      evolution may have already occurred in AML/TMDS, as MDS transformed to AML is
      associated with clonal evolution.

PMID- 9592184
TI  - One step direct detection of recurrent mutations in the breast cancer
      susceptibility gene, BRCA1.
AB  - Germ-line mutations of the BRCA1 gene have been linked to 85% of hereditary
      breast and ovarian cancers. More than one hundred mutations have been reported,
      including several which are over represented within the Ashkenazi Jewish
      (185delAG) and Irish families (1294del40). These recurrent mutations are cost
      effective targets for presymptomatic screening of cancer susceptibility. Most
      current techniques such as single strand conformation polymorphism, heteroduplex
      analysis, DNA sequencing, and protein translation termination assays are
      multistep, time consuming methods and require radioactive isotopes for mutation
      detection. As an alternative, we have developed a single step, non-radioactive
      allele specific oligonucleotide (ASO) PCR assay designed to target any known
      mutation. Its application to detection of the BRCA1 185delAG and 1294del40
      mutations is described here. The ASO PCR is efficient, highly sensitive, non
      radioactive, specific for individual mutations, performed in a single step, and
      is amenable to large-scale screening for other known mutations.

PMID- 9592185
TI  - The tetramerization domain-independent Ras activation by BCR-ABL oncoprotein in
      hematopoietic cells.
AB  - BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase
      activity and is implicated in the pathogenesis of Philadelphia chromosome
      positive human leukemias. We have previously shown that BCR-ABL activates Ras
      signaling pathways required for transformation. To elucidate the mechanisms
      whereby BCR-ABL induced transformation in hematopoietic cells, we examined the
      biological effects of expression of a series of BCR-ABL mutants. We found that
      the Grb2 binding site-deleted BCR-ABL and the SH2 domain-deleted BCR-ABL, as well
      as the tetramerization domain-deleted BCR-ABL do not diminish the transforming
      properties of BCR-ABL in hematopoietic cells, although these mutations were
      previously shown to drastically reduce the transforming activity of BCR-ABL in
      fibroblasts. The tetramerization domain-deleted BCR-ABL did not induce tyrosine
      phosphorylation of CrkL, SHP-2, Vav and the interactions of BCR-ABL and Shc.
      However, Ras is activated, Shc is tyrosine phosphorylated and binds to Grb2 in
      the tetramerization domain-deleted BCR-ABL expressing hematopoietic cells. These
      results suggest that the tetramerization domain-independent Ras activation is
      mediated by Shc proteins and induces the transformation of hematopoietic cells.

PMID- 9592186
TI  - HVJ (Sendai virus) liposome-mediated gene transfer: current status and future
      perspectives (review).
AB  - Haemagglutinating virus of Japan (HVJ; Sendai virus), a member of the mouse
      paramyxovirus family, has been combined with liposomes to produce a novel gene
      transfer system, namely HVJ liposomes. This vector system is defined as a <hybrid
      vector>, constructed with inactivated viral particles and non-viral (artificial)
      multi- or unilamellar liposomes containing gene expression cassettes and has
      several advantages in comparison with other viral or non-viral systems. Many
      studies have shown that this vector system can, not only produce efficient gene
      transfer using reporter genes, but also with resulting in vivo functional changes
      in several animal models of diseases. Despite these results, it is likely that
      the construct will need to be modified to improve gene transfer and expression
      efficiency and also to extend the potential disease targets. We review the
      present status of this hybrid vector system and also discuss possible
      modifications for future application to either in vivo analysis of specific gene
      expression or human gene therapy strategies for congenital or acquired diseases.

PMID- 9592187
TI  - Galectin-3 expression in human breast carcinoma: correlation with cancer
      histologic grade.
AB  - Galectins (S-type lectins) are a family of low-molecular weight, calcium
      independent, mannose-binding lectins with functions in cell growth, cell
      activation, cell-cell and cell-matrix adhesion including binding to
      carcinoembryonic antigens and laminin and metalloproteinase. Anti-galectin
      antisera can inhibit metastases of rat prostate cancers and human melanomas. To
      define the role of galectins in human breast cancer, the expression of galectin-3
      were determined in 27 invasive breast cancers by immunohistochemical methods. The
      histologic grades of excised breast cancers were determined and
      immunohistochemical staining for galectin-3 (1: 1000 dilution of anti-galectin
      rat polyclonal antibody) was defined by scoring the intensity and distribution of
      staining (0-3+). The mean age of breast cancer patients was 63 years for 20 grade
      II breast cancers and 56 years for 7 grade III breast cancers. The mean
      immunohistochemical staining score for grade II breast cancers was 3. 7 (20% less
      than 2, 80% 3-6) and 2.5 for grade III (71.4% less than 2 and 28.6% 3-6). The
      galectin-3 expression pattern suggests that increasing histologic grade of breast
      cancer leads to reduced expression of galectin-3 and possibly reduced matrix
      binding and increased cancer cell motility.

PMID- 9592188
TI  - Identification of cytochrome P450s in human glioma cell line.
AB  - Five different isoforms of cytochrome P450 including 1A1, 1A2, 2E1, 2A and 2B6
      have been identified in human glioma Hs 683 cell line using RT-PCR reaction.
      These isoforms belong to four distinct subfamilies. The effect of benzanthracene
      (Ba) as inducer was tested on the mRNA level of cytochrome P450 1A1. Northern
      blot analysis clearly showed an induction response from these cells to Ba in a
      proportion that is comparable to the induction seen in rat glioma cells.

PMID- 9592189
TI  - Elevated concentrations of mitochondrial peripheral benzodiazepine receptors in
      ovarian tumors.
AB  - Using PK 11195, a high affinity ligand for peripheral benzodiazepine receptor
      (PBZr) binding sites in isolated mitochondria (m-fraction) and microsomal
      fraction (p-fraction) from human ovaries and ovarian tumors were studied. Binding
      in both m and p-fractions from ovaries and tumors were saturable and of high
      affinity. The PBZr density in m- and p-fractions from ovaries was very similar
      whereas the binding in m-fraction in ovarian tumors was nearly 3-fold higher than
      p-fraction. There was no significant difference in the binding affinities (KD
      values) for PK 11195 in the various fractions. The selective increase in the
      density of PBZr in mitochondria of tumors suggests an association with energy
      demand and utilization. The role of a relatively high density of PBZr in
      microsomal fractions remains to be elucidated.

PMID- 9592190
TI  - 3F8 monoclonal antibody treatment of patients with stage 4 neuroblastoma: a phase
      II study.
AB  - 3F8 is an IgG3 murine monoclonal antibody directed against the ganglioside GD2.
      In a phase II study, 3F8 was administered i.v. to 16 patients (pts) who had stage
      4 neuroblastoma. Response was seen in bony lesions (2 of 7 pts) and marrow (3 of
      8 pts). Acute toxicities of pain, fever, urticaria, hypertension, hypotension and
      anaphylactoid reactions were self-limited and manageable. Three pts are long-term
      survivors between 79-130+ months after 3F8 treatment without additional systemic
      therapy and no delayed neurological complications. The potential benefits of 3F8
      when added to chemoradio-therapy warrant further investigation.

PMID- 9592191
TI  - Dephosphorylation of Vav is associated with the induction of mouse
      erythroleukemia cell differentiation: effects of orthovanadate and levamisole.
AB  - Mouse erythroleukemia (MEL) cell erythroid differentiation induced by dimethyl
      sulfoxide or hexamethylene bisacetamide (HMBA) is accompanied by the production
      of hemoglobin, terminal cell division and decreases in lactate production and
      fructose 2,6-bisphosphate levels. A number of studies have suggested that
      decreases in the cellular level of protein phosphotyrosine content may play a
      role in MEL cell differentiation. In particular, it was shown that the expression
      of several protein tyrosine phosphatase genes accompany this process and that the
      transfection of one of these genes into MEL cells followed by its subsequent
      expression induced eythroid differentiation. However, none of the physiological
      substrates for these protein tyrosine phosphatases have been identified. It is
      shown here that MEL cell differentiation is accompanied by decreases in tyrosine
      phosphorylation of Vav and possibly of the erythropoietin receptor (EpoR).
      Immunoprecipitation of the EpoR and analysis of co-precipitated proteins,
      indicates that the EpoR associates with Vav, STAT5 and an unidentified 60 Kd
      protein, . HMBA-induced erythroid differentiation abrogates these associations.
      The phosphatase inhibitors, Na3VO4 and levamisole, inhibit HMBA-induced
      differentiation as well as the association of the EpoR with Vav, STAT5 and the 60
      Kd protein. This is of interest since Na3VO4, at the concentrations used here,
      has been shown to be a potent inhibitor of the activity of protein tyrosine
      phosphatases. These results suggest that levamisole, at least indirectly, acts by
      a molecular mechanism similar to that of Na3VO4 and that the loss of the
      association of the EpoR with Vav, STAT5, and and/or the reduction in the level of
      tyrosine phosphorylation of these proteins may play a role in MEL cell
      differentiation.

PMID- 9592192
TI  - Reduced expression of mismatch repair genes in colorectal cancer patients in
      Egypt.
AB  - An Egyptian hospital-based pilot case-control study was conducted to investigate
      the relationship between the expression level of mismatch repair (MMR) genes and
      the risk of colorectal cancer. The relative expression of five known MMR genes,
      i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex
      reverse transcriptase (RT)-polymerase chain reaction (PCR) in peripheral blood
      lymphocytes from 31 colorectal cancer patients and 47 age- and-sex matched
      controls. The expression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower
      in patients than controls, but only the difference in hPMS2 expression was
      statistically significant (p<0. 01). Although 50% of the cases had chemotherapy
      or radiotherapy within the last six months before the blood was drawn, their gene
      expression was not statistically different from those who had not undergone such
      therapies. After adjustment for age and sex, the odds ratios (OR) calculated from
      a logistical regression model, using the median levels of gene expression of
      controls as cut-off values, indicated that increased risk was associated with
      reduced expressions of both hPMS1 (OR = 3.97, 95% confidence interval (CI) = 1.04
      to 7.65) and hPMS2 (OR = 2.86, 95% CI = 1.05 to 7.76). Although the results of
      this study were inconclusive because of the small sample size and use of
      prevalent cases, it is biologically plausible that patients with colorectal
      cancers may have a lower expression of MMR genes than healthy controls because
      malfunction of these genes has been shown in hereditary nonpolyposis colon
      cancer. The involvement of low hPMS2 expression in colon cancer risk seems to be
      unique in the Egyptian population. Further studies with newly diagnosed patients
      before they begin therapy will provide more convincing data about the role of MMR
      gene expression in the etiology of colorectal cancers in Egypt.

PMID- 9592193
TI  - The herbal medicine sho-saiko-to inhibits the growth of malignant melanoma cells
      by upregulating Fas-mediated apoptosis and arresting cell cycle through
      downregulation of cyclin dependent kinases.
AB  - The anti-tumor effect and its mechanism of the herbal medicine sho-saiko-to were
      investigated on a murine malignant melanoma cell line (Mel-ret). Sho-saiko-to
      induced apoptotic cell death of Mel-ret cells with a definite increase of cell
      surface Fas antigen and Fas ligand (FasL). Sho-saiko-to arrested Mel-ret cells in
      G1 phase by decreasing the expression of cyclin-dependent kinase (cdk) 4 and its
      homologue cdk6. Kinase activities of cdk4 and cdk6 were identified to be
      downregulated by sho-saiko-to. Ingredient analysis revealed that baicalin is
      likely the main active constituent in the upregulation of Fas antigen and Fas
      ligand, while glycyrrhizin is the main constituent in the inhibition of cdks.

PMID- 9592194
TI  - Clonality analysis of cervical cancer on microdissected archival materials by PCR
      based X-chromosome inactivation approach.
AB  - Clonality of invasive human cervical cancer was assessed in microdissected
      archival formaldehyde-fixed, paraffin-embedded tissues by PCR-based analysis of X
      chromosome inactivation of the androgen receptor gene. In 18 informative cases,
      cancers from 12 cases including 2 early-invasive cancers were scored as
      monoclonal. Among them, 8 cases had the combination of random X-chromosome
      inactivation in normal cervical tissue and non-random in the cancer and in other
      4 cases normal and cancer tissue were both non-random but had discordant X
      chromosome inactivation. Six cases showed that the non-random inactivation
      affected the same allele in cancer and normal tissue and thus were considered to
      be inconclusive. The results suggest the monoclonal origin of cervical cancer and
      indicate that genetic events are critical in transition of pre-malignant
      epithelia to invasive cancer in cervical carcinogenesis. Finding of monoclonal
      early invasive cancer also argues that monoclonality of human tumors is not a
      late event due to clonal competition or selection. X-chromosome inactivation
      patterns in normal cervical epithelia and tissues were analyzed in 21 informative
      cases. When a mixture of normal stroma and epithelium was analyzed, 38% (8/21) of
      cases showed non-random inactivation pattern, whereas using pure epithelium it
      was 64% (11/17). The X-chromosome inactivation pattern between mixed
      epithelium/stroma and matched epithelium differed in 2/8 cases. These results
      point to a certain amount of overlooked source of error in X-inactivation-based
      tumor clonality analysis in which peripheral blood monocytes were chosen as
      control and strongly recommend that control tissues which share close
      histological origin with analyzed tumors should be selected in any clonality
      study of human neoplasm. Post-embryological mechanisms of clonal patch in normal
      cervical epithelia are also discussed.

PMID- 9592195
TI  - Detection of ras gene mutations in peripheral blood of carcinoma patients using
      CD45 immunomagnetic separation and nested mutant allele specific amplification.
AB  - We developed a sensitive technique of detecting circulating tumor cells in
      carcinoma patients, using CD45 immunomagnetic separation to isolate epithelial
      cells in blood samples and specific polymerase chain reaction analysis to
      identify point mutations of the K-ras gene. The method is based on the fact that
      the peripheral blood mononuclear cells (PBMC) that express CD45 antigen are
      trapped with anti-CD45 conjugated supramagnetic microbeads while the carcinoma
      cells that do not express CD45 antigen are not trapped and pass through the
      magnetic fields. This method concentrated the number of carcinoma cells 3.3
      times. After this separation, the modified method of mutant allele specific
      amplification was applied and this method was able to ten control carcinoma cells
      in a background of 107 PBMC. A preliminary clinical study demonstrated that six
      cases of end-stage carcinoma with K-ras mutations in the primary tumor showed the
      same mutations in the peripheral blood samples, while two cases without K-ras
      mutation in the primary tumor and 10 healthy volunteers showed no mutation in the
      peripheral blood samples. The results suggest that this method may be very useful
      to detect circulating carcinoma cells in the patient whose primary tumor shows K
      ras mutations.

PMID- 9592197
TI  - Matrix metalloproteinases in cancer: prognostic markers and targets for therapy
      (review).
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which catalyse
      degradation of diverse substrates in the extracellular matrix. The family can be
      loosely divided into 4 subgroups, i.e., interstitial collagenases, gelatinases,
      stromelysins and membrane-type MMPs. Data from model systems suggest that MMPs
      are involved in both stimulating tumor cell growth and promoting invasion and
      metastasis. Consistent with their role in tumor progression, high levels of
      certain MMPs have been shown to correlate with poor prognosis in different human
      cancers. Inhibitors of MMPs prevent or decrease tumor progression in model
      systems and are currently undergoing evaluation for the treatment of human
      cancers.

PMID- 9592196
TI  - Involvement of caspase family proteases in FPT inhibitor III-induced apoptosis in
      human ovarian cancer cells.
AB  - We have previously demonstrated that a new farnesyltransferase inhibitor, FPT
      inhibitor III, triggers apoptosis in human ovarian cancer cells. Here, we report
      that induction of apoptotic cell death in PA-1 ovarian cancer cells by FPT
      inhibitor III was accompanied by the activation of interleukin-1 #-converting
      enzyme (ICE)-like proteases, which have recently been renamed as caspases. The
      caspase inhibitor, ZVAD-FMK, which inhibits a number of caspase family proteases,
      blocked FPT inhibitor III-induced apoptotic cell death in a dose-dependent
      manner. Additionally, cleavage of poly(ADP-ribose) polymerase, an identified in
      vivo substrate for caspase family proteases, in FPT inhibitor III-treated cells
      was confirmed by immunoblotting. Our results suggest that the caspase family
      proteases are involved in the induction of apoptosis triggered by FPT inhibitor
      III.

PMID- 9592198
TI  - Protein kinase C and its isoforms in human breast cancer cells: relationship to
      the invasive phenotype.
AB  - Total protein kinase C (PKC) activity and the expression of 9 isoforms were
      determined in the estrogen receptor (ER) positive MCF-7 human breast cancer cell
      line, this line transfected to overexpress either PKC-a or erbB2, and in 3 ER
      negative breast cancer cell lines. Relationships were sought between PKC and the
      expression of E-cadherin, alpha-catenin, and vimentin, and urokinase-type
      plasminogen activator (uPA). In general, PKC enzymic activity and the
      conventional isoforms PKC-alpha and -gamma were higher in the ER negative,
      compared with the ER positive, cell lines. Over-expression of PKC-alpha by MCF-7
      cells, with ER loss, was associated with the emergence of PKC- expression and a
      relatively high level of PKC-gamma, features typical of cells with increased
      proliferation rates; there was also a loss of PKC-delta, consistent with
      acquisition of the metastatic phenotype. Transfection to overexpress erbB2, with
      ER retention and slowed growth, produced a decrease in PKC-alpha and -gamma.
      Vimentin was expressed by the ER negative MDA-MB-231, MDA-MB-435 and PKC-alpha
      transfected MCF-7 cells; they also showed loss of E-cadherin and, apart from MDA
      MB-435 cells, high levels of uPA secretion. The ER negative SKBr-3 cell line was
      exceptional in that it had relatively low total PKC activity, low PKC-alpha and 
      gamma expression and no emergence of vimentin despite loss of E-cadherin
      expression. Compared with the other two ER negative cell lines, both the SKBr-3
      and MDA-MB-435 cells had low PKC activity and uPA secretion. These results are
      consistent with the involvement of PKC, and notably the conventional isoforms, in
      the development of the metastatic phenotype, and specifically with the loss of E
      cadherin and acquisition of vimentin expression, and the enhanced production of
      uPA.

PMID- 9592199
TI  - Activation-induced cell death in human peripheral blood lymphocytes after
      stimulation with silicate in vitro.
AB  - Silica and related substances such as silicate have been proven to possess
      "adjuvant effects". We have previously reported a finding of polyclonal human T
      cell activation induced by silicate as a superantigen in vitro. In this study, we
      observed activation-induced cell death in human lymphocytes after stimulation
      with chrysotile, a kind of silicate. Apoptotic cells were detected flow
      cytometrically using the TUNEL assay, and the maximum appearance of TUNEL
      positive cells occurred on day 4 of incubation. Simultaneously the manifestation
      of small-sized cells in the specimens increased implying apoptosis. Fas
      expression on lymphocytes increased to day 3 of incubation with chrysotile, and
      then spontaneously decreased on day 4 when remarkable apoptosis could be
      detected. Based on these results it is conceivable that activation-induced cell
      death occurred through Fas-Fas ligand interaction in lymphocytes after
      stimulation with silicate in a concentration with which no acute cytotoxicity has
      been detected. Whether and how the repeated apoptosis in definite clones of
      lymphocytes causes the induction of sFas synthesis need clarification.

PMID- 9592200
TI  - The efficacy of 2',2'-difluorodeoxycytidine (gemcitabine) combined with
      interferon in human renal cell carcinoma cell lines.
AB  - The present in vitro study on three human renal cell carcinoma (RCC) cell lines
      (A-498, ACHN, SN12C) evaluated the efficacy of 2',2'-difluorodeoxycytidine (dFdC,
      gemcitabine), vinblastine (VBL), rhu-interferon-alpha (IFN-alpha) and rhu
      interferon-gamma (IFN-gamma) alone or in combinations. The cytotoxicity was
      measured by using the sulphorhodamine B colorimetric cytotoxicity assay. Analyses
      were made from cells being continuously long-term (4 weeks) or short-term (4 h)
      with IFN-alpha or IFN-gamma with regard to the cytotoxicity of the
      chemotherapeutic agents. dFdC was more cytotoxic against ACHN and A-498 cells
      compared to VBL. Pre-treatment with IFN-alpha enhanced growth inhibition caused
      by dFdC (4/4 cell lines) and VBL (2/3 cell lines), and was more effective than
      IFN-gamma. Pre-exposure with IFN-alpha sensitized SN12C and ACHN cells for dFdC.
      A-498 cells achieved a decreased sensitivity to dFdC and VBL after pre-exposure
      to IFN-gamma. The resistance of newly established dFdC-resistant SN12C cells (23
      times) decreased when pre-treated with IFN-alpha. The data demonstrate efficacy
      of dFdC in human RCC at concentrations below clinically achievable doses. dFdC
      was more effective compared to VBL. Combined therapy preferentially with IFN
      alpha increased cytotoxicity of dFdC in vitro. In vivo studies in nude mice
      xenografts are under investigation to support these observations.

PMID- 9592201
TI  - The efficacy of 2',2'-difluorodeoxycytidine (gemcitabine) and vinblastine
      combined with interferon in nude mice xenografts of human renal cell carcinoma.
AB  - Recent in vitro experiments indicated strong activity of 2',2'
      difluorodeoxycytidine (dFdC, gemcitabine) in human renal cell carcinoma (RCC)
      cell lines and an increase of efficacy by combined application of interferon
      (IFN). In the present study, nude mice with xenografts from ACHN- or SN12C cells
      were treated by dFdC, dFdC plus IFN-alpha or vinblastine (VBL) plus IFN-alpha.
      ACHN-xenografts were significantly more inhibited by dFdC+/-IFN-alpha than by
      VBL+IFN-alpha. Complete remissions (CR) were only seen by dFdC. An additional
      treatment with IFN-alpha shortened the time to commencement of tumor remission
      and increased CR of ACHN- and SN12C-tumors (40%; 7%) compared to a treatment with
      dFdC alone (20%; 0). dFdC+IFN-alpha reduced the number of pulmonary metastases
      compared to untreated animals. Survival was significantly prolonged by dFdC+/-IFN
      alpha in ACHN-mice and dFdC+IFN-alpha or VBL+IFN-alpha in SN12C mice. In
      conclusion, experimental data confirm dFdC as a superior drug against human RCC
      compared to VBL. Combined therapy with IFN-alpha increased the efficacy of dFdC
      in terms of tumor response in immunodeficient nude mice, thus clinical studies
      are strongly recommended in patients with metastatic renal cell carcinoma.

PMID- 9592202
TI  - Pathology of sporadic breast tumors with LOH at the BRCA1 locus: correlation with
      histopathological features specific to familial BRCA1 tumors and absence of
      microsatellite instability.
AB  - To investigate the coordinated occurrence of loss of heterozygosity (LOH) at the
      BRCA1 locus and microsatellite instability (MI) in sporadic breast carcinomas, 56
      tumors were analysed for both genetic alterations. The comparison of
      clinicopathological features with the obtained data revealed that LOH at the
      BRCA1 locus was significantly correlated with features specific for familial
      BRCA1 tumors and with absence of hormone receptors. No correlation was found
      between LOH and MI. These results suggest that sporadic and familial breast
      tumors, where BRCA1 is altered, could display similar clinicopathological
      features and that LOH and MI are distinct genetic events in sporadic breast
      carcinogenesis.

PMID- 9592203
TI  - The in vivo enhancement of IL-1alpha receptor expression on polyoma virus
      transformed tumor derived cells.
AB  - The aim of this study was to evaluate expression of receptor for IL-1 on tumor
      derived cells. The in vivo acquisition of an expression of a receptor for Fc c
      immunoglobulin on polyoma virus transformed cells has been established by us. We
      investigated whether a receptor for the IL-1 cytokine, like that for Fc gamma
      immunoglobulin, could also contribute to the heterogeneity of tumor cell
      population, as well as to its tumorigenic phenotype. Various clones of polyoma
      virus transformed 3T3 cells were passaged once in syngeneic mice and resulting
      tumors explanted and recultured. The expression of receptor for IL-1 was tested
      on in vitro maintained clones (designated C for culture) and on tumor derived
      clones (designated CTC - culture-tumor-culture). Expression was determined using
      a 125I radiolabeled ligand and confirmed by flow cytometry with anti-mouse IL-1
      receptor (IL-1R) antibodies. Some CTC clones expressed a higher level of IL-1
      receptor than others. A positive correlation between the level of IL-1R and a
      metastatic phenotype was established with some tumor derived cells. A high IL-1R
      expressing tumor cell population, sorted by flow cytometry, was considerably more
      metastatic than the sorted low IL-1 expressing cells. IL-1R expression by tumor
      derived cells may, contribute to the metastatic phenotype of a tumor cell
      population.

PMID- 9592204
TI  - No evidence for constitutional ATM mutation in breast/gastric cancer families.
AB  - Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disease characterised
      by cutaneous telangiectasia, cerebellar ataxia, immunodeficiency, high
      sensitivity to ionising radiation, chromosomal instability and an increased risk
      of cancer. The gene mutated in A-T patients, ATM, is located on chromosome 11q22
      23. ATM heterozygotes are thought to have a high tendency to develop
      malignancies, such as breast cancer. In order to determine the contribution of
      heterozygous ATM mutation to cancer, studies of cancer-affected patients have
      been undertaken in non site-specific cancer families and sporadic breast cancer
      cases. No evidence of an important role of ATM heterozygous mutations has been
      shown. In order to give another contribution to these results, we tried to define
      a specific family phenotype according to the most common cancers observed in ATM
      heterozygotes. Breast and gastric cancers appear to be the most frequent
      malignancies in A-T carriers and one ATM germ-line mutation has been described in
      a breast/gastric cancer family. Therefore we further investigated the role of ATM
      mutation in additional breast/gastric cancer families. In eighteen families
      associating these two malignancies, we used the protein transcription/translation
      test to detect ATM mutations in the index case from each family. We found one
      case of ATM mutation which did not cosegregate with the gastric cancer in the
      family.

PMID- 9592205
TI  - A novel approach to glioma gene therapy: down-regulation of the vascular
      endothelial growth factor in glioma cells using ribozymes.
AB  - Glioblastoma multiforme is one of the most highly vascularized solid neoplasms,
      therefore treatments that target neovascularization process would be of great
      clinical importance. Studies of glioblastoma angiogenesis have revealed that
      expression of the vascular endothelial growth factor (VEGF) is up-regulated in
      these tumors. Previous reports have shown that down-regulation of VEGF correlates
      with modification in the glioma growth. To examine this phenomenon further, in
      this study we constructed two hammerhead ribozymes (RZI and RZII) to target the
      5' common region of VEGF mRNA. Both ribozymes exhibited site-specific cleavage to
      a 318-nucleotide VEGF transcript and showed a high digestion efficiency in vitro
      (65-95%). After the transfection of glioma cells with two expression vectors
      carrying the ribozyme sequence, Northern blot analyses detected high levels of
      ribozyme expression. Treatment of the glioma cells with the ribozymes resulted in
      a reduction in VEGF mRNA in six of eight clones. Furthermore, the anti-VEGF
      effect was confirmed at protein level. Thus, enzyme-linked immunoabsorbent
      analyses (ELISA) showed a >70% reduction in the VEGF165 expression level. These
      results indicate that hammerhead ribozymes may be useful in down-regulating VEGF
      expression and suggest that anti-VEGF strategies may be used to potentiate other
      gene therapies targeting tumor suppressor genes.

PMID- 9592207
TI  - [Editorial]

PMID- 9592208
TI  - [Durkheim's Suicide: reassessment of a classic from 19th-century sociological
      literature]
AB  - This paper presents a detailed review of Suicide, the sociological classic by
      Durkheim, 100 years after it was first published, The first part of the article
      focuses on the author's interest in the theme, within the scope of concerns on
      the importance of studying suicide dating from the 18th century. The article then
      presents a circumstantial review of the various chapters, preceded by brief
      remarks on the book's place within Durkheim's work as a whole. The third part of
      the article comments on the book with reference to the main autors that have
      studied it. Amongst other qualities, the book's importance lies in the fact that
      it associates an elaborate theoretical construction with the empirical data,
      working within the possibilities provided by late 19th-century moral statistics.
      The article stresses Durkheim's perspective of dealing with the impact of the
      macrostructures over micro-level phenomena. The distribution of suicides is also
      reviewed, updating information and the relationship between suicides and
      professional groups, for example. The paper also provides a critique of authors
      who stress the importance of 'meanings' in the analysis of suicides, with some
      notes on the relationship between suicide and mental disease.

PMID- 9592209
TI  - [The complexity of relations between drugs, alcohol, and violence]
AB  - This article discuss the complex relations between drugs and violence. Drawing on
      empirical studies and current forms of discourse, it analyzes conceptual and
      methodological problems related to the establishment of causal nexuses, risks,
      and associations. By demonstrating the theoretical and practical difficulties in
      such associations, it also points to the need for a debate in the field of public
      health and social policies. The article expresses concern that programs and
      prevention not be contaminated by fallacies, contributing nothing to an
      understanding of (or action related to) the social issue of drugs.

PMID- 9592206
TI  - Regulation of cell proliferation and urokinase plasminogen activation of human
      breast epithelial cells by carrageenans.
AB  - Carrageenans, a family of polysulphated carbohydrates, are able to inhibit the
      binding to cells of growth factors such as transforming growth factor 1 (TGF 1),
      fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor (PDGF) and
      so modulate cell invasion and proliferation. We studied the effects of
      carrageenans on the proliferation and on the uPA/PAI-1 system in breast
      epithelial cells. Carrageenans were able to inhibit the proliferation of both
      normal breast epithelial cells (NBEC) and breast epithelial cancer cell lines
      (MDA-MB-231 and MCF-7) but could only inhibit the uPA activity in the MDA-MB-231
      cells. Moreover, carrageenans inhibited FGF-2 binding in all three cell types,
      suggesting that they regulate cell proliferation and uPA/PAI-1 system through two
      distinct mechanisms. These molecules could be considered as potentially useful
      anti-cancer agents.

PMID- 9592210
TI  - [Medical auditing: procedures assessment in the women's integral health care
      program in the Vila Municipal Health Clinic, Pelotas, Rio Grande do Sul, Brazil]
AB  - This study is based on a medical audit of the Vila Municipal Health Clinic,
      Pelotas, Rio Grande do Sul. We collected data from family medical records in
      1992,1993, and 1994. The data concerned the Women's Integral Health Care Program.
      We collected information on age, visits for medical and non-medical reasons,
      blood pressure, breast examination, coverage of Pap smear testing, and
      contraceptive methods. On average, women visited the clinic 3.5 to 4 times a
      year; 53% of the women were between 20 and 39 years of age; 42.5% of the women
      had had a Pap smear in the previous three years; 19% of the women had had their
      breasts examined. Blood pressure measurement was the most common procedure
      recorded in this clinic. We believe quality of medical records is a factor in
      patient care. We expect a critique of the low-quality medical records found in
      this audit can serve as the basis for a discussion among the health care team,
      with a view towards improving medical care, thereby benefiting patients.

PMID- 9592211
TI  - [The effects of Leprosy on men and women: a gender study]
AB  - On the basis of social representations, we detected gender differences in family
      and individual living experiences for people with Hansen's disease (HD, or
      leprosy) in a sample of 202 HD patients (132 men and 70 women) enrolled in a
      public treatment and control program in Ribeirao Preto, Sao Paulo State.
      Information was gathered in two stages. First, the HD patients responded to a
      structured questionnaire, and second, the authors heard reports from 10 men and
      10 women on their daily living situations. Data indicated that the disease
      receives different representations by men as compared to women in the different
      social groups. HD was found to be a source of gender imbalance, further
      aggravating existing sociocultural inequalities and creating new sources of
      biopsychosocial and economic harm, in addition to the stigmata weighing on
      individual patients. Results should help reorient treatment and control programs
      aimed at the social rehabilitation of HD patients, besides serving as a paradigm
      for future research

PMID- 9592212
TI  - [Quality-of-care assessment in a university hospital pediatric clinic]
AB  - This study focuses on the Pediatric Clinic of the UNICAMP University Hospital,
      teaching and care facility belonging to the Brazilian National Health System,
      providing secondary and tertiary health care for children aged 0 to 18 years. A
      total of 221 questionnaires were applied with users of the general pediatric out
      patient services and one of the specialties, allowing for comparison of various
      medical care indicators. Users were found to be quite knowledgeable about their
      health conditions and satisfied with the care received, despite a weak link in
      the physician-patient relationship. 43.4% reported problems related to the
      services, while only 17.6% made suggestions to improve them. Waiting time was
      found to be quite long. Users of specialized services differed from general care
      patients with regard to several indicators.

PMID- 9592213
TI  - [Analysis of Services Targeting Family Violence Against Women in Greater
      Metropolitan Buenos Aires, Argentina]
AB  - This study presents a diagnosis and evaluation of the availability of services
      related to family violence against women in Greater Metropolitan Buenos Aires,
      Argentina. The paper focuses on institutional development, theoretical foci,
      intervention modalities, and production of information and research. Existing
      networks and interprofessional relationships are also described. Results point to
      several noteworthy theoretical perspectives. Some programs include gender as an
      issue, while others do not. The relationship (more informal than formal) between
      governmental and nongovernmental organizations is also a relevant issue. The
      paper concludes by proposing these institutional experiences as a model for the
      design of new public health policies.

PMID- 9592214
TI  - [Adequacy of drug advertisements distributed to prescribers in Southern Brazil]
AB  - Drug advertisements for prescription drugs gathered from private clinics and
      hospitals in southern Brazil were analyzed. None of the 127 advertisement inserts
      that were analyzed complied with all the criteria specified by Brazilian
      legislation. The official Brazilian generic drug name was present in 95% of the
      advertisements, but always in finer and/or fainter print. With regard to the WHO
      ethical criteria for medicinal drug promotion the study showed that only 59% of
      the advertisement inserts declared the product composition and only 43% provided
      information on precautions, and in most of these cases (73%(, the precautions
      were in fine print and difficult to read. Most of the advertisements declared the
      product dosage in more properly-sized print. The main advertising claims were
      efficacy, safety, faster action, and high tolerability. In conclusion, the
      analysis demonstrated that most advertisements fail to comply with either the
      Brazilian legislation on medicinal products and/or the WHO ethical criteria for
      medicinal drug promotion. To improve this situation it thus seems necessary to
      develop more effective instruments to monitor quality of information provided to
      prescribers by the drug advertisers.

PMID- 9592215
TI  - [Elements for changing a prevailing psychiatric care model]
AB  - This study presents the results of research done at the Pedro II Psychiatric
      Center in 1995, as part of a partnership between the Center and the Universidade
      do Estado do Rio de Janeiro. Research includes the development of a profile for
      inpatients based on clinical and socioeconomic data from patient files, emergency
      ward assessment of the group's interactive abilities based on WHO parameters, and
      a critical analysis of the psychiatric care model employed in the Psychiatric
      Center. With the psychiatric reform pursued by major sectors of Brazilian society
      we intend not only to respond to the economic/administrative irrationality
      created by 'hospital-centrism', but especially to meet the needs of patients,
      health professionals, and society in general in moving away from a psychiatric
      care model dominated by the reference patterns of psychiatry and to de
      institutionalize mental health. The results of this study criticize the
      biomedical model and open the door to a care model engaged in psychosocial
      rehabilitation. The critical analysis based upon the data from the investigation
      done at the Psychiatric Center should be applicable to other psychiatric
      hospitals in Brazil's public and private sectors.

PMID- 9592216
TI  - [Sociodemographic and behavioral factors related to schistosomiasis in a rural
      village of the sugar cane belt in Pernambuco State, Brazil]
AB  - Failure of intensive chemotherapy to control schistosomiasis in a highly endemic
      area of Northeast Brazil led to the hypothesis that sociodemographic and/or
      behavioral variables could be involved in the persistent transmission. A
      univariate analysis of such variables in relation to infection by Schistosoma
      mansoni showed that water contact patterns for recreation and personal hygiene
      are important risk factors in the area. However, sociodemographic variables were
      not related to infection, probably because the local population lives under
      evenly precarious socioeconomic and sanitary conditions. We thus recommend that
      chemotherapy be combined with other measures like snail control, health
      education, and improved sanitation and water supply.

PMID- 9592217
TI  - [Evaluation of a program for asthmatic children treated in primary care
      outpatient units in Embu, Sao Paulo, 1988-1993]
AB  - The main objective of this study was to evaluate the effectiveness of the Program
      Targeting Children with 'Chest Wheezing' carried in the city of Embu, Sao Paulo.
      The study analyzed a total of 434 children aged zero to 14 years, admitted to the
      program from May 1988 to July 1993. Over 90% had never been treated for this
      medical problem in outpatient clinics. Only 6.2% had to be referred to other
      health care services during follow-up in this program. The program successfully
      performed clinical diagnosis of asthma in children over 2 years of age. The
      moderate and severe cases followed up for over a year showed the best clinical
      evolution, with the positive factor being better compliance with medication. The
      number of exacerbations decreased among the severe patients after a year of
      regular follow-up, although patients used bronchodilators during the 12 months of
      our analysis. Of the children enrolled, 53.2% gave up treatment principally in
      the first six months, most of them from the moderate group. We concluded that
      children with steadier compliance with the program benefited in spite of both the
      simplicity and the lack of some currently existing medications.

PMID- 9592218
TI  - [Schistosomiasis epidemiological patterns in a community of small farmers in
      Pernambuco State, Brazil]
AB  - This article is part of a larger study in which epidemiological and
      anthropological methods were used to help understand the production and
      maintenance of schistosomiasis in a small endemic area in Pernambuco State. A
      cross-sectional study identified several local risk factors for schistosomiasis,
      quantifying socioeconomic, sanitary, and behavioral variables and then relating
      them to the prevalence and intensity of schistosomiasis infection. Using
      univariate analysis, three variables (age group, schooling, and human/water
      contact) showed significant association with S. mansoni infection. Causal factors
      and confounding variables were identified through multivariate analysis.
      Quantitative epidemiological analysis is critically discussed regarding a
      qualitative ethnographic study in relation to environmental risk situations
      (contamination and transmission) as well as risk practices (economic and
      behavioral).

PMID- 9592219
TI  - [An educational intervention to improve the quality of coproparasitological
      diagnosis in laboratories of Havana City, Cuba]
AB  - The aim of this study was to evaluate the effectiveness of an educational program
      carried out in 1993. The intervention took place after the first external quality
      assessment in coproparasitology, conducted in 77 laboratories of Havana City.
      Centers receiving training were compared with those that did not, and better
      results were obtained in the municipalities of 10 de Octubre, Plaza, and Cerro,
      as well as in all laboratories that sent people to training. Better diagnosis was
      found for the helminths Trichuris trichiura, Taenia sp., and Fasciola hepatica as
      well for the protozoans Blastocystis hominis and Endolimax nana in the
      laboratories that received training. The laboratories that received training had
      significantly higher scores than those which did not. The results point to the
      effectiveness of the educational intervention. We recommend external quality
      assessment in coproparasitology as well as ongoing, mandatory technical
      education, held at regular intervals. Such measures should assure steady
      improvement in diagnosis of intestinal parasites by the health services network.

PMID- 9592220
TI  - [Gender and sexuality: fragments of male identity in the Aids era]
AB  - This paper focuses on specific aspects of male sexuality and how this sexual
      identity is built in the Aids era, based on conversations with low-income youth,
      ages 14-21 years, living in Greater Metropolitan Rio de Janeiro. We examine how
      Aids is perceived and investigate sexuality in this epidemic context. The goal is
      to provide concrete data to support a prevention campaign and contribute to
      preventive policies in Brazilian society. The proposal is based on the sexual
      identity of this gender/age group, comparing their reports on sexual practice. We
      used a partially open-ended interview protocol. We focus on the way young males
      choose their sexual identity under the premise that this is how men can become
      the channel for Aids transmission. Our research was thus based on gender and
      sexual identity as categories. Our results indicate that for a young man, 'being
      a man' means having an active sexual life, thus creating a stereotype placing
      them at risk for HIV transmission.

PMID- 9592221
TI  - [Nutritional status and socioeconomic factors associated with failure in school:
      a prospective study of first grade students in Belo Horizonte, Brazil]
AB  - This study aimed to establish a correlation between anthropometric and
      socioeconomic variables and repetition in school for first grade pupils, as well
      to determine the predictive value of such variables vis-a-vis repetition. A study
      with a prospective and concurrent approach was developed in four elementary
      schools in Belo Horizonte, Minas Gerais State, with 699 children (95% of those
      eligible). After adjustment for confounders, children whose mothers had less than
      eight years of schooling, of mothers with unskilled jobs, from single-parent
      households (mother, father, or guardian), whose per capita family income was less
      than or equal to half the minimum wage, and who had a height/age/sex index under
      the 10.1 percentile were at greater risk of repeating the first grade. The data
      are potentially useful for selecting children to be monitored and to prevent
      repetition in the schools investigated.

PMID- 9592222
TI  - [Mortality trends for acute rheumatic fever and chronic rheumatic heart disease
      in Venezuela, 1955-1994]
AB  - This study reports on deaths due to acute rheumatic fever (ARF) and chronic
      rheumatic heart disease (CRHD) in Venezuela from 1955 to 1994. Census
      publications and other official sources provide the population data. Yearly age 
      and sex- specific mortality rates per 100,000 inhabitants were calculated and
      adjusted by the direct method to the WHO's standard population. The RF-adjusted
      mortality rate (AMR) declined: total from 7.68 to 1.08 (-85.9%); male from 7.53
      to 0.84 (-88.8%); and female from 7.83 to 1.33 (-83.0%). In all cases female RF
      AMRs were higher than male. There was a reduction of 88.5% in the ratio of RF
      deaths to cardiovascular deaths (ICD-6330-334,400-447; ICD-7330-334,400-447; ICD
      8 390-438; ICD-9 390-438). ARF-AMR declined (-93.5%) as did CRHD-AMR (-85.1%).
      Proportional death by ARF and CRHD in patients 45 years old and younger
      increased. Venezuela experienced a continuous decline in RF-AMR from 1955 to the
      l980s, followed by a period of stabilization lasting until l994. The reduction
      could be the consequence of improvement in socioeconomic status and of RF
      prevention with penicillin, a standard practice in the health care system. The
      1980s and 1990s RF-AMR stabilization could be associated with economic setbacks
      in Venezuela and changes in the agent's virulence patterns.

PMID- 9592223
TI  - [School meal programs as a mean to meet nutritional requirements for students in
      the Integrated Public School Centers]
AB  - This study evaluates food intake of 244 children between ages 7-13 years using
      records of ingested foods on three non-consecutive days. The study analyzes
      energy and nutrient adequacy based on standards for the Brazilian population.
      Diet was generally found to be energy-deficient: meals consumed at the CIEPs met
      less than 70% of the requirement. On the other hand, protein was well above
      recommended levels. Worthy of note was the adequacy of meals in the CIEPs as to
      vitamin A, thiamin, riboflavin, and niacin, as well as the surprising adequacy of
      ascorbic acid, resulting from the frequent presence of citrus fruits in school
      meals. Except for older students, all schoolchildren studied had greater than 90%
      minimum iron intake. As for calcium, again except for older ones, consumption was
      100% or more of minimum required levels. Results showed the need to correct flaws
      in the nutritional content of school meals, which are central to dietary intake
      for CIEP students.

PMID- 9592224
TI  - [Triatominae species]
AB  - This paper provides a checklist of 15 known species of the Triatominae subfamily
      in Maranhao State. On the coastal Sao Luis Island there are a total of 10 species
      associated with sylvatic areas (Eratyrus mucronatus, Psammolestes tertius,
      Panstrongylus diasi) and periurban and urban areas (Panstrongylus geniculatus,
      Panstrongylus lignarius, Rhodnius nasutus, Rhodnius neglectus, Rhodnius pictipes,
      Rhodnius robustus and Triatoma rubrofasciata). The last was found only on Sao
      Luis Island, while the others have also been found inland. The following were not
      found in the coastal area: Panstrongylus megistus, Triatoma brasiliensis,
      Triatoma maculata, Triatoma pseudomaculata and Rhodnius brethesi. These were
      found mainly on the 'Chapadas' and 'Chapadoes' areas in the eastern and southern
      parts of the State.

PMID- 9592225
TI  - [Analysis of non-prescription drug radio advertising in Rio Grande do Sul State,
      Brazil]
AB  - Drug advertisements for non-prescription (over-the-counter) drugs on the main
      radio stations in the State of Rio Grande do Sul, Brazil, were analyzed as to the
      information provided about generic names, pharmaceutical company, composition,
      and dosage. From August 1995 to January 1996, 250 advertisements for 28 products
      were recorded. More than 80% of these advertisements provided no information on
      these topics and thus failed to comply with Brazilian legislation. On the
      contrary, a large number of advertisements (39%) emphasize absence of risks, with
      claims such as "no contraindications" inducing consumers to use such drugs
      indiscriminately. The study showed that drugs were advertised like any other
      merchandise with no concern over fundamental information such as product
      identification, precautions, and possible side effects.

PMID- 9592226
TI  - [Can models be built on the basis of the relationship between social contexts and
      health?]
AB  - As more is known about the complexity of the relationships between social,
      economic, and environmental contexts and the health of the population, it appears
      clear that the concepts of illness and health, while not independent, are not
      synonymous. A major challenge now facing the field of public health is to
      organize a true dialogue between the life sciences working mainly on illness seen
      as a disturbance in one of the functions of a living organism and human sciences
      dealing with a population's health. Society's challenge is to grant each
      individual access to high-quality health care services when needed, while
      developing public policies to promote the health of the population as a whole.

PMID- 9592227
TI  - [Alternative foods: a critical analysis of a proposal for nutritional
      intervention]
AB  - The nationwide use of a 'Multimixture' a formula based on alternative foods such
      as rice and/or wheat bran, sesame and squash seeds, cassava, beet and carrot
      leaves, several indigenous leafy vegetables, and ground egg shells has been
      proposed by the National Institute of Food and Nutrition (INAN) as an official
      solution to fight hunger among poor Brazilians. The fragile nutritional state of
      the target population may make technical or ethical questions appear purely
      academic, yet nutritional, toxicological, and practical feasibility
      considerations appear to warrant a revision of the INAN proposal. While the
      Multimixture approach may prove valid as a temporary solution in cases of extreme
      poverty, it is not universally applicable for the intended use, failing to take
      into account the age and nutritional status of the subjects or duration of the
      intervention.

PMID- 9592228
TI  - [Retrospect of past eighty years].

PMID- 9592229
TI  - [The importance of the standardization of scientific nomenclature in
      physiological sciences].

PMID- 9592230
TI  - [Helicobacter pylori: a great discovery].
AB  - Within the past decade, there has been an explosion of investigative activity and
      publications about Helicobacter pylori pathogen. Its role in gastroduodenal
      diseases is becoming remarkably evident. It is accepted that H. pylori is
      intimately involved in the pathogenesis of chronic gastritis microbiol/DT and
      peptic ulcer disease. Furthermore, it is also associated with stomach cancers.
      The old creed in medical field that "No acid, no ulcer" would probably be changed
      to "No H. pylori infection, no ulcer". So, the discovery of H. pylori
      revolutionized our understanding of gastroduodenal diseases.

PMID- 9592231
TI  - [Cyclin-dependent kinase inhibitors in mammal cells].
AB  - In recent two years, a group of protein factors have been found to combine with
      the cyclin-dependent kinases (CDKs) and block the activation of cyclin/CDK
      complexes. They are named CDK inhibitors (CKIs) as p21, p16, p15, p27 and CDI1.
      The p21 and p27 have certain homology and can inhibit the activity of multiple
      CDKs; p16 and p15 have higher homology and can specifically combine with CDK4 and
      CDK6; and the combination specificity of CDI1 needs further research. The
      expression of p21 is regulated positively by p53. TGF-beta can upregulate the
      expression of p15 and the inhibitory activity of p27. The above findings
      demonstrate that CKIs are not only the regulators of CDKs' activity but also the
      direct linkers between cancer inhibitors and cell-cycle regulation.

PMID- 9592232
TI  - [Current status of the application of patch-clamp technique and its combinations
      with other techniques].
AB  - The Patch-clamp technique, as an advanced electrophysiological technique, has
      been widely used for research in the life science research field. A recent trend
      is to combine this technique with other techniques, such as the Fura-2
      microfluorimetry for measuring the concentration of Ca2+, electrochemical
      detection with carbon-fiber electrode (i.e. amperometric detection or
      amperometry), and single-cell reverse transcription of RNA followed by the
      polymerase chain reaction (RT-PCR). This article is to summarize the current
      status of the use of patch-clamp technique and its combinations with other
      techniques in solving problems related with transmembrane signal transduction in
      neurobiology.

PMID- 9592233
TI  - [Role of neural cell adhesion molecule and polysialic acid on the neuronal
      development and regeneration].
AB  - The formation of nervous system depends on intercellular adhesion. This review
      covered the role of neural cell adhesion molecule (NCAM) and its polysialic acid
      (PSA) moiety on the neuronal development and regeneration. Mediation of cell
      adhesion is the fundamental role of NCAM, while the existence of PSA on NCAM
      decreases cell adhesion by its specific structure. It is known that during the
      development of chick embryo, the expression of PSA at three critical phases
      determines whether motoneurons can accurately innervate muscle. Following the
      peripheral nerve lesions of adult rats, the expression of NCAM is regulated by
      the state of innervation of muscle. In the adult rat brain, the disconnection of
      entorhinal cortex and hippocampus results in the elevation of PSA in the outer
      molecular layer of the dentate gyrus, with this increased expression remains for
      at least 60 days after lesion. Existing data strongly suggest that the
      reexpression of PSA in the denervated area may promote axonal outgrowth of
      transplanted neurons and reconstruct synaptic connection with host.

PMID- 9592234
TI  - [Interaction of sugar with phospholipid bilayer--study on the stabilization of
      liposomes].
AB  - Sugars have the capacity to stabilize structure and function of lipid bilayer. In
      the presence of sugars, liposomes could remain in their intact biological
      structure and retain as much as 100% of their original contents after drying
      rehydration circle. In this review we present molecular mechanism of preserving
      effect of sugars on lipid bilayer: preventing membrane fusion, affecting the main
      transition temperature, preventing lateral phase separation and phase transition
      of L alpha to H(I). This paper also describes the prospect of the application of
      these studies.

PMID- 9592235
TI  - [Progress in the study of chymase].
AB  - Chymase is a kind of serine proteinase, mainly exists in secretory granules of
      mast cell and extracellular interstitium. The mature enzyme is a glycoprotein
      comprising 226 amino acid residues, with molecular weight of 30 kD. It can be
      inhibited by serine proteinase inhibitors but not by angiotensin I converting
      enzyme inhibitors. The cDNA and genomic DNA of human chymase were cloned and
      sequenced. Chymase has close relations with neurogenic inflammation,
      extracellular matrix catabolism, control of vasoactive peptide metabolism, and so
      on. It plays an important role in angiotensin II formation in human heart.

PMID- 9592236
TI  - [Comparative study on the expression and interaction of oncogene c-fos/c-jun and
      three opioid genes induced by low and high frequency electroacupuncture].
AB  - The present work was designed (a) to study comparatively the effect of 2Hz and
      100Hz electroacupuncture (EA) on the expression of oncogene c-fos/c-jun and three
      opioid (preproenkephalin-PPE; preprodynorphin-PPD; proopiomelanocortin-POMC)
      genes in the rat brain; (b) to clarify the role of Fos/Jun (AP-1) on opioid genes
      expression induced by EA stimulation through specific blockade of EA-induced
      Fos/Jun expression using antisense oligodeoxynucleotides (ODNs) of c-fos/c-jun.
      The results were: (a) 2Hz and 100Hz EA induced differential Fos expression in
      different brain areas; (b) EA of both frequencies accelerated PPE gene
      transcription, but 2Hz EA was more effective than 100Hz EA; (c) PPD expression
      was accelerated by 100Hz EA, but not by 2Hz EA; (d) the blockade of Fos/Jun
      expression by c-fos/c-jun antisense ODNs prevented EA from accelerating PPD but
      not PPE mRNA expression.

PMID- 9592237
TI  - [Studies on the anti-aging and nootropic effects of ginsenoside Rg1 and its
      mechanisms of actions].
AB  - It has been well documented that ginsenoside Rg1 is one of the important active
      principles of ginseng and shares many pharmacological effects of this drug, such
      as facilitating learning and memory and alleviating many ailments associated with
      aging. In the present studies, Rg1 was found to selectively enhance the
      deteriorated immune function in aged animals, ameliorate age-related alterations
      in both behavior and motor response, promote hippocampal neuronal function of
      aged rats, and provide partial protection against the excitotoxic effect of
      glutamate. All of these provide several aspects of explanation to elucidate Rg1's
      anti-aging and nootropic mechanisms.

PMID- 9592238
TI  - [A new domain of interleukin-2 and its analgesic effect in central nervous
      system].
AB  - Interleukin-2 (IL-2) possesses not only immunoregulatory activity, but also
      important effect on central nervous system (CNS). Here we report that IL-2 is an
      analgesic molecule in CNS and suggest that there are two distinct domains in IL-2
      that mediate immune and analgesic activity. It is inferred that the analgesic
      effect of IL-2 in CNS is mainly mediated through the analgesic domain which is
      composed of the 45th Tyr-residue, the 44th, 117th Phe-residues and other residues
      around the 45th-Tyr in tertiary structure, directly binding to the opioid
      receptors. In addition, we propose that the multiple actions of cytokines might
      be mediated by interaction of distinct domains with different receptors or
      receptor subtypes.

PMID- 9592239
TI  - [The function of myogenin and its regulation].

PMID- 9592240
TI  - [Progress in the study of mechanisms regulating vascular smooth muscle cell
      proliferation].

PMID- 9592241
TI  - [Genetic control of programmed cell death].

PMID- 9592242
TI  - [Molecular biological studies on brain ischemia].

PMID- 9592243
TI  - [NO and nociceptive processing].

PMID- 9592244
TI  - [FLT3/FLK2: a novel member of tyrosine kinase receptor family].

PMID- 9592245
TI  - [ATP: a neurotransmitter].

PMID- 9592246
TI  - [Pyrroloquinoline quinone and its physiological effects].

PMID- 9592248
TI  - [31P-nuclear magnetic resonance in vivo].

PMID- 9592247
TI  - [Advances in the research of germanium].

PMID- 9592249
TI  - [Evaluation of clinical and pathological factors relating to lymph node
      metastasis in carcinoma of the tongue].
AB  - In this paper we adopt various clinical and pathological parameters to evaluate
      the factors relative to the lymph node metastasis. We are of the view that the
      TNM classification can not indicate the presence of the lymph node metastasis
      clearly. When the size of tumor is less than 2.0 cm in diameter there is almost
      no metastasis. Using computer, we analyse the factors and found that only the
      depth, pattern of growth and the degree of lymphoid cell infiltration are
      relative to metastasis. The coincidence is 78.6%.

PMID- 9592250
TI  - [Report of clinical use of fixed-removable prosthesis].
AB  - Thirty-two patients provided with the fixed-removable prosthes is were followed
      up 3 month to 2.5 years. A total of 52 abutments were included, 17 of which were
      telescopic retainer, 14 were bar attachment retainer, 4 were rod attachment, 12
      were stud attachment and 5 were slide attachment. Few technical failures were
      recorded. All found the prosthesis satisfactory and well functioning.

PMID- 9592251
TI  - [The effect of Gynostemma pentaphyllum mak (GP) on carcinogenesis of the golden
      hamster cheek pouch induced by DMBA].
AB  - The purpose of the study is to examine the effect of GP during carcinogenesis of
      the golden hamster cheek pouches induced by DMBA. The results indicated that
      epithelial olysplasia and carcinoma in situ appeared respectively at 3 and 6
      weeks. The formation of carcinoma was detected as early as 4 weeks which is
      earlier than that of former reports. The experiment proves that GP has positive
      anticarcinogenic function. Long-term observation in those the DMBA has been
      applied for 3 weeks found that epithelial dysplasia could reverse when GP was
      given. A compound prescription is better than GP alone.

PMID- 9592252
TI  - [Experimental study of adoptive immunotherapy for adenoid cystic carcinoma of the
      salivary gland].
AB  - To study adoptive immunotherapy for adenoid cystic carcinoma of the salivary
      gland, we evaluate the influence of TNF-alpha or IFN-gamma on the activity of LAK
      cells when they acted at different stages of LAK cells killing target cells. The
      results in vitro experiment showed that ACC-2 was susceptible to LAK
      cytotoxicity. Both TNF-alpha and IFN-gamma could be an enhancer to augment IL-2
      induced LAK cytotoxity against ACC-2, TNF-alpha should be used to induce LAK
      cells, but IFN-gamma is suitable to pretreat target cells ACC-2.

PMID- 9592253
TI  - [Histopathological effects of overextended opening of the mouth on the
      temporomandibular joint and masticatory muscles].
AB  - The purpose of this study is to explore the effects and the pathogenicity of
      overextended mouth opening on the temporomandibular joint (TMJ) and the
      masticatory muscles. In this experiment, the animal model of overextended opening
      was, established by overly opening the miniature pigs' mouths for certain periods
      with mouth gag, and then the TMJ and the masticatory muscles were studied
      histopathologically. The results showed that the histosytes of the TMJ and the
      masticatory muscles had suffered injury, proliferation, atrophy and degeneration
      from the overextended opening, and the extents of deterioration became greater
      with the increase of frequency and duration of overextended opening. Among the
      injured tissues, the cartilage of the condyle, the posterior and anterior
      portions of the articular disc, the anterior extenting tissue of the disc, the
      lateral perygoid muscles and the temporalises underwent the most obvious
      histopathological changes. The result of this study confirms that overextended
      mouth opening is one of the pathogenic factors of CMD, and it has great
      significance for the clinical diagnosis, treatment and prevention for CMD.

PMID- 9592254
TI  - [Expression of Bcl-2 gene product in oral lymphoma of mucosa associated lymphoid
      tissue].
AB  - Bcl-2 (B cell leukemia/lymphoma-2), one of apoptosis-suppressing genes, can
      inhibit apoptosis of both some normal and tumor cells, and is related to the
      development of some tumors. In present study, the expression of bcl-2 was
      examined in 26 cases of oral lymphomas of mucosa associated lymphoid tissue
      (LMALT) using immunohistochemistry. The results showed that 73% of LMALT were
      positive to bcl-2 antibody. Among three main histological subtypes, the small
      cleaved cell type demonstrated highest positive persentage (83%), followed by
      lymphoplasmacytoid lymphoma (71%) and lymphoplasmacytic lymphoma (51%). In
      respect to immunological subtypes, bcl-2 was detected in 69% of B cell lymphoma,
      75% of T cell lymphoma, and 83% of lymphomas which could not be classified by
      present immunohistochemistry repectively. The results indicated that the
      inhibition of apoptosis might not be one of reasons for the development of some
      LMALT.

PMID- 9592255
TI  - [Magnetic resonance imaging of the TMJ disc in asymptomatic volunteers].
AB  - To determine whether disc displacement of temporomandibular joint exists in
      asymptomatic subjects in China, we examined fifty temporomandibular joints (TMJs)
      of 39 asymptomatic volunteers by magnetic resonance imaging (MRI). All subjects
      had no history of TMJ pain, joint noise, deviation, and opening limitation,
      Oblique sagittal and coronal MR images were obtained by scanning perpendicular
      and paralell to the longitudinal axis of the condyle respectively. MR imaging
      depicted anterior, medial and rotational disc displacement in 32% of the
      asymptomatic joints. Disc displacement in asymptomatic subjects may be a
      predisposing factor of TMJ dysfunction.

PMID- 9592256
TI  - [Expression of proliferating cell nuclear antigen and tumor suppressor gene P53
      in mucoepidermoid carcinoma of salivary glands].
AB  - To explore the expression of proliferating cellnuclear antigen (PCNA) and tumor
      suppressor gene P53 product in mucoepidermoid carcinoma of the salivary glands,
      we studied 41 cases by immunohistochemical method. All of the cases were PCNA
      positive. The positive index, distribution pattern and cellular staining
      intensity for PCNA expression were correlated with carcinoma grade. P53 protein
      expression was found in 17 (41.5%) of the 41 cases; among them the expressions
      were weak in 9 cases. These results indicate that positive index, distribution
      pattern and cellular staining intensity of PCNA expression may be served as an
      indicator for evaluating the differentiating degree of the tumor.

PMID- 9592258
TI  - [Application of monoclonal antibody immuno-colloide gold probe in the study of
      porphyromonas gingivalis].
AB  - Immuno-electron localization of McAb BGG9 was specific for Porphyromonas
      gingivalis labeled with colloide gold. The monoclonal antibody immuno-colloide
      gold probe reacted with Porphyromonas gingivalis and 5 species of black pigmented
      bacteroides groups. The bacteria were fixed and embbed in Epon. sections were
      examined under transmission electron microscope, and the gold granular was
      observed near Porphyromonas gingivalis cell membrane. Our conclusion suggests
      that monoclonal antibody immuno-colloide gold probe is useful tool for studying
      Porphyromonas gingivalis.

PMID- 9592257
TI  - [Effects of interleukin-1 on the differentiation of osteoblasts].
AB  - By use of quantitative histochemistry, effects of interleukin 1 (IL1) on the
      differentiation of osteoblasts derived from neonatal rabbit calvaria were
      studied. The results showed that IL 1 inhibits the alkaline phosphatase activity
      in the cultured osteoblasts. Also, both quantitative immunohistochemistry study
      and radioimmunoassay study showed that IL-1 has the ability to stimulate
      osteocalcin production and secretion in the cultured osteoblasts. Our results
      suggest that IL 1 plays a role in the regulation of osteoblastic differentiation,
      and in the end inhibits the calcification of bone matrix.

PMID- 9592259
TI  - [The micro-anatomy and clinical significance of the apical foramen in 1,282
      permanent teeth].
AB  - To study the shape and size of the apical foramen of permanent teeth and their
      relations, we observed 1,282 permanent teeth. The teeth were photographed by XTL
      2 photstero microscope. The rule of its shape and its clinical significance were
      discussed. In the 1,282 teeth, the round and oralshaped accounted for 94.77%
      (1,215/1,282), indicating that the morphological appearance of the apical foramen
      is inconsisted with that of vessels or/and nerves in the tissues.

PMID- 9592260
TI  - [Mesencephalic trigeminal nucleus neurons innervate both the masticatory muscles
      and the periodontal ligaments: a fluorescent double-labeling study in rats].
AB  - The mesencephalic trigeminal nucleus (Vme) neurons are primary sensory neurons
      transmitting orofacial proprioceptive sensation. The neurons innervating the
      periodontal ligaments and the masticatory muscles are intermingled with each
      other in the caudal part of the Vme. After fluorescent tracers, propridium iodide
      and bisbenzimide were applied to the inferior alveolar nerve and the masseter
      nerve on the same side of the rat, and a doubled-labeled neurons were observed in
      ipilateral Vme, mainly in the caudal part, and a few in the middle, rostral part.
      This reflects simultaneous innervation of both the periodontal ligaments and the
      masseter spindles by collaterals of peripheral process of single Vme neurons.

PMID- 9592261
TI  - [Analysis of serum osteocalcin of patients with periodontitis].
AB  - To evaluate the effect of bone formation on alveolar bone destruction in
      periodontitis, we selected 20 patients with severe chronic periodontitis (CP),
      and 9 patients with rapidly progressive periodontitis (RPP). Their serum
      osteocalcin was determined by radioimmunoassay (RIA). The serum osteocalcin in
      65.0% patients with CP and 66.7% patients with RPP was lower than that in normal
      persons. It is suggested that osteoblastic activity and bone formation ability of
      periodontitis patients are lower than those of normal persons. The alveolar bone
      destruction in periodontitis results from not only increased osteoclastic
      activity and bone resorption but also decreased osteoblastic activity and bone
      formation.

PMID- 9592262
TI  - [The effect of tinidazole in the treatment of adult periodontitis].
AB  - Fifty-two adult periodontitis patients were treated by the tablets of tinidazole
      (TNZ), and 23 patients treated by metronidazole (MNZ) served as control group.
      The effective rate of TNZ in adult periodontitis patients was 73.1%, which was
      significantly higher than that of the control group (43.5%). Antimicrobial
      studies showed that the capability of TNZ to kill the periodontal dominant
      anaerobic bacteria, especially B. gingivalis and B. melaninogenicus, was better
      than that of MNZ. The minimal inhibitory concentration (MIC) of TNZ to
      Bacteroides, Fusobacterium, Veillonella, Eubacterium, Antinomyces,
      Peotostreptococus and Anaerobic Streptococus was lower than that of MNZ and
      actylspiramycine.

PMID- 9592263
TI  - [Traumatic facial nerve injury in rabbits: a quantitative pathologic study].
AB  - Six kinds of facial nerve injury in 136 facial nerves of 68 rabbits were studied
      by quantitative pathology. The ratio of intrafascicular axon crossing and the
      ratio of intrafascicular area can reflect the extent of the lesions for non-cut
      injury (exposure, compression, stretch and crush) effectively. However, the ratio
      of mesial to distal intrafascicular area should be combined for the evaluation of
      cut injury (division and anastomosis). The mean optical density (F1), axon area
      (F13), and homogeneous degree (F49) can reflect quantitatively the form and
      extent of the single axon lesion and its content. The morphologic parameter (F10)
      can reflect the change of axon morphology. The results of quantitative pathologic
      study support the histopathologic study, and provide additional knowledge about
      the progress of serial axon lesions.

PMID- 9592264
TI  - [Vascular changes of temporomandibular joint in relation to its diseases].

PMID- 9592265
TI  - [The sialographic characteristics of Warthin tumor in the parotid gland].
AB  - The sialograms of 80 cases with Warthin tumor in parotid gland were analysed. The
      sialographic characteristics were found as follows: irregular arrangement,
      dilation and narrow of branch ducts which surrounded the tumor, sausagelike
      change of main ducts just like that seen in obstructive parotitis, and spot-like
      dilation of the terminal ducts. The comparative study on roentgen-pathology
      showed that the spot-like dilation of the terminal ducts was related to the
      dilation of interlobular duct of the gland surrounding the tumor. The roentgen
      differential diagnosis of Warthin tumor from the aggressive benign tumor and
      Sjogren syndrome is discussed.

PMID- 9592266
TI  - [Sialochemistry in nonneoplastic diseases of parotid gland: immunoglobulins and
      electrolytes].
AB  - The concentration and total value of immunoglobulins (SIgA, IgG) and electrolytes
      (sodium, potassium, chlorine, calcium and phosphorus) in mixed saliva were
      examined in 28 patients with Sjogren's syndrome (SS), 25 with chronic obstructive
      parotitis (COP), 32 with sialadenosis and 32 normal controls. The results showed
      that in SS group, total saliva flow rate was decreased: concentration of SIgA,
      IgG, electrolytes was significantly elevated; but total value of SIgA, IgG,
      electrolytes was markedly decreased. Decreased total value of sodium, potassium,
      chlorine and calcium was revealed in COP group. Elevated concentration and total
      value of phosphorus was found in sialadenosis group. This study indicates that
      examination of total value of immunoglobins and electrolytes has greater value
      than that of concentration. The possible mechanism of changes observed is
      discussed.

PMID- 9592267
TI  - [Superoxide dismutase and malonyl dialdehyde in human pulp tissue].
AB  - A total of 21 pulps were collected from 12 inflamed and 9 normal cases. SOD
      activity and MDA content were identified in the normal and inflamed pulpal
      tissues. In the inflamed pulpal tissues, SOD activity and MDA content were
      significantly increased than those in the normal tissues. The results
      demonstrated that the inflammation of pulpal tissues resulted in the increasing
      of the reactivity of superoxide radical and lipid peroxide (LPO). The results
      also indicated that human dental pulp possessed an endogenous defense mechanism
      to protect the tissue components from the toxic effects of the reactive oxygen
      intermediates.

PMID- 9592268
TI  - [Alveolar reconstruction in patients with cleft palate].
AB  - Repair of the alveolar cleft is one important procedure in team approach of cleft
      palate. The present paper reports 110 cases repaired by bone grafting.
      Indications, technique, results evaluation and management before and after
      operation are discussed. The study proves that bone grafting is effective to
      repair alveolar cleft and should be popularised. Properly forming the bed of bone
      grafting and perfectly closing the receipt site are the keys of success. Patients
      should be treated orthodontically before and after operation. In selection of
      donor site, the patient's age, tooth age, width of cleft and quantity of bone to
      be grafted should be considered.

PMID- 9592269
TI  - [Study of skeletal and occlusal pattern].
AB  - The aims of this study were to analyze the characteristics of craniofacial
      structure in normal occlusion and to assess the relationship between the skeletal
      and occlusal pattern. Fifty-seven subjects with normal occlusion were divided
      into three skeletal groups according to Hauston measurement. One hundred and
      sixty-six subjects with Angle's malocclusion were also classified according to
      ANB values. The result showed that there were significant differences in the
      values of NA-APg, AB-NPg, SNA, SNB, U1-NA, L1-NB among the three groups. These
      data indicate that skeletal pattern does not coincide with occlusion. Different
      skeletal pattern exists even in normal occlusion. In diagnosis and treatment
      planning, the data of skeletal pattern should be referred.

PMID- 9592270
TI  - [Clinical evaluation about restoration for cervical wedge-shaped defects of teeth
      using composite and dentin bonding].
AB  - 100 cervical wedge-shaped defects of teeth with normal pulp from 19 patients were
      restored with light cure composite (durafill). For each patient, teeth of one
      side were experimental group, the other side were the control group, and left or
      right side was alternatively changed randomly. For the experimental group, the
      restorations of 49 teeth were adhered by Gluma dentin bonding. For the control
      group, the restorations of 51 teeth were adhered by Durafill bonding. The results
      of 2 years follow-up study with modified USPHS evaluation criterion indicate that
      curative effects, including retention and marginal sealing in the experimental
      group are much better than those in the control group.

PMID- 9592271
TI  - [Study on stress distribution of the condyle].
AB  - The stress distribution in the condyle was calculated by means of combining CT
      examination with computed image operating technique and three-dimensional finite
      element models. The results suggested that there was a higher stress level in
      condylar cortical bone than in cancellous bone. Stress on the cortical bone were
      shown to concentrate in middle and lateral 1/3 part of articular surface of the
      condyle. The distribution of stress on two condyles was symmetrical. That
      analysis method of biomechanics was introduced into the clinical and baic study
      on the temporomandibular joint provided a new means for helping diagnosis and
      treatment of the temporomandibular joint diseases.

PMID- 9592272
TI  - [The inhibitory effect of TNF-alpha on alkaline phosphatase activity of human
      periodontal ligament fibroblasts].
AB  - The present investigation was to identify the impact of recombinant human tumor
      necrosis factor-alpha (TNF-ALPHA) on alkaline phosphatase (ALP) activity of
      cultured human periodontal ligament fibroblasts (HPLF). It was found that, after
      treatment with TNF-alpha, HPLF in the experimental groups showed significantly
      lower ALP activity than in the blank control groups (P < 0.01). Further, the ALP
      activity was observed to decrease progressively with increasing TNF-alpha
      concentrations. These findings indicate that TNF-alpha possesses a remarkable
      concentration-dependent inhibitory effect on human periodontal ligament
      fibroblasts.

PMID- 9592273
TI  - [A new speech training method for patients following cleft palate repair].
AB  - A new method of speech training in Chinese was established according to
      investigations of articulatory phonetics and speech pathology of 50 patients
      following cleft palate operations. All of these patients were examined thoroughly
      and were considered to have good velopharyngal function. However, in all of them,
      the articulation score was lower than 70%. 33 of these 50 patients were treated
      with the method for a period of 22 to 120 days (average 63 days). Results showed
      that their articulation improved from 38.4% to 89.5% on average, the improvement
      in speech was highly significant statistically (P < 0.0001). In addition, the
      question of correct timing for speech therapy is discussed.

PMID- 9592274
TI  - [An electromyographic study of the exposed lateral pterygoid muscle in monkey].
AB  - The purpose of the present study is to observe the electromyogram (EGM)
      manifestations of the lateral pterygoid muscle (LPM) in monkey during mouth
      opening and closing movements. The lateral pterygoid muscle of five healthy
      monkeys (macaques) was exposed by operation under general anesthsia and the
      electropolar needles were placed into the superior and inferior head of LPM
      respectively. The EMG manifestations of the superior and inferior head of LPM
      were recorded by O.T.E. Biomedica EMG Recorder during the natural condition and
      the movements of opening and closing mouth after complete recovery from
      anesthesia. It has been found that the two heads acted synergistically only in
      opening movement and no activity was noted in closing movement. This finding
      disagrees with the previous viewpoint that the function of the superior and
      inferior head of LPM is independent.

PMID- 9592275
TI  - [Color analysis of Vita shade guide].
AB  - In order to understand the reliability of the Vita Shade Guide and make it more
      resonably in applying, a series of tests were accomplished. Three Vita shade
      guides were selected in Beijing hospitals. By using the international color
      standard CIE1976LAB color system and CS-5 Spectrocolorimeter to measure, test and
      analyse the characteristics of the shade guides including the degree of color,
      color distribution, color stability and color difference. The results indicate:
      The tabs of each shade guide demonstrated the greatest color stability; most of
      the average color difference among the same number tabs of each guide are less
      than 1.5 NBS and the color range of shade guides are more limited than that of
      Chinese teeth crown.

PMID- 9592276
TI  - [Histochemical and electronic microscopical studies of stellate fibrillar
      formations (SFF) in salivary gland tumors].
AB  - PURPOSE: To study the structure and significance of SFF in pleomorphic adenoma
      and myoepithelioma. MATERIAL AND METHODS: Tow cases of each tumor were studied.
      Histologie and ultrathin sections were made, stained with HE, Mallory, Van
      Gieson, Pollak methods, and examined with light and transmission electronic
      microscopes. RESULTE: The SFF were proved to be formed by radial arrangement of
      collagen fibers, which were composed of striped fibrillae under TEM. CONCLUSION:
      The structure of the SFF is understood, their existence may play a role the
      pathologic diagnosis.

PMID- 9592277
TI  - [Experimental study on repair of mandibular defect by allogenic decalcified bone
      compounded with autogeneic bone marrow in rabbits].
AB  - Twenty adult rabbits were used in our experiment. The bone defects were made at
      the lower border of the bilateral mandible. A compound bone graft (allogenic
      decalcified bone with autogeneic bone marrow, ADB) was implanted in the right
      bone defect as the experimental group. The left mandible was taken as the control
      group and autogeneic cancellous bone was grafted. The process of new bone
      formation was evaluated by X-ray plain film, 99Tc-PYP Scintigraphy, histological,
      and histochemical, and transmmission electronic microscope examinations. The
      results demonstrated histogically that ADB induced new bone formation. The
      quantity of new bone produced by compound bone graft in the experimental group
      was much more than that in control group (P < 0.05). The compound bone graft can
      promote and accelerate bone defect healing.

PMID- 9592278
TI  - [Fibronectin in tissues and saliva of patients with oral lichen planus].
AB  - By means of immunohistochemistry (ABC), morphometric analysis and
      radioimmunoassay, the changes of fibronectin in saliva and tissues in 30 patients
      with oral lichen planus were investigated. The results indicated that the
      distribution forms of fibronectin had changed before the quantity changed.
      Fibronectin level was lower in saliva of oral lichen planus patients when
      compared with normal control group. We estimated that fibronectin may play an
      important role in occurrence and development of the oral lichen planus. The
      recurrent and unheal erosion may be related to the changes of fibronectin.

PMID- 9592279
TI  - [Significance of the expression of HLA-DR on keratinocytes in oral lichen planus
      lesions].
AB  - In this article, the expression of HLA-DR in keratinocytes in lesions of oral
      lichen planus (OLP) was investigated, using an immunohistochemical technique (PAP
      method). The results showed: HLA-DR positive keratinocytes were found in all
      groups of patients, the numbers and expressive degree of HLA-DR were related to
      types and duration of OLP, there were higher statistically significant
      differences between different groups and types of OLP (P < 0.01). The authors
      considered that the expression of HLA-DR in keratinocytes plays an important role
      in gathering T cells and forming inflammation in OLP lesions.

PMID- 9592280
TI  - [Expression of the PAC gene of S. mutans in S. lactis].
AB  - Expression of the pac gene in S. lactis were analyzed by dot immunoblotting with
      rabbit anti-PAc serum. The amount of PAc produced by S. lactis HL107 (pLF107) was
      measured. This result indicated that a small amount of rPAc was detected in the
      culture supernatant and cell homogenate of S. lactis HL107 (pLF107) but not in
      the control strain S. lactis LM0230. The amount of rPAc in S.lacits HL107
      (pLF107) was six times lower than that in S. mutans Ingbritt. Expression of
      cloned pac gene in S. lactis was also confirmed in this result.

PMID- 9592281
TI  - [A simplified theory of protrusive balanced occlusion in complete denture and its
      application].
AB  - Based the study of the theory of protrusive balanced occlusion in complete
      denture construction and clinical experience the author established a new
      simplified theory named "the three principle factors and three laws for
      protrusive balanced occlusion in complete denture" to guide us to arrange teeth
      for balanced occlusion in complete denture construction. Based this theory the
      phenomena of protrusive occlusal disharmony appeared in the process of teeth
      arrangement and denture insertion can be corrected easily.

PMID- 9592282
TI  - [Location of the surface protein antigen I/II on Mutans Streptococci with
      immunogold electron microscope].
AB  - Mutans Streptococci possess a number of surface protein antigens. The surface
      protein antigen I/II with a molecular mass of 190,000 is considered to play an
      important role in the initial attachment to tooth surface. The antigen is highly
      immunogenic and has been successfully used as a vaccine against dental caries.
      The object of this study is to locate the surface protein antigen I/II of Mutans
      Streptococci with immunogold electron microscope. The results suggest that (1)
      antigen I/II locate on the cell wall surface of serotype c, e, f; (2) antigen
      I/II locate on the "fuzz coat" of the cell wall of serotype d, g; (3) some
      antigen I/II locate at the surface of cell wall of serotype a; (4) antigen I/II
      are absent on the cell wall surface of serotype b strain.

PMID- 9592283
TI  - [Radiographic findings in osteoarthrosis of temporomandibular joint in relation
      to its pathologic changes].
AB  - We analysed the results of the central standard lateral tomographic findings and
      the macroscopic/microscopic observations on the middle portion of the autopsy
      materials of 84 temporomandibular joints. It was not suitable to differentiate
      remodeling and osteoarthrosis of the temporomandibular joint only by whether the
      surface articular zone of the articular cartilage is intact or not. The early
      changes of osteoarthrosis could occur in the interface of the bone-cartilage
      except occuring in the articular zone, even though the surface articular zone was
      intact. Therefore, we suggest that the definition of osteoarthrosis should be
      wider. Histopathologic observations proved that the definte radiographic signs,
      such as sclerosis, erosion, pseudocyst, osteophyte and so on showed on the
      lateral tomographs were credible signs in the diagnosis of osteoarthrosis.

PMID- 9592284
TI  - [The relationship of function and pathology of submandibular gland with
      sialolithiasis].
AB  - Submandibular glands with sialolithiasis are analysed histopathologically. The
      formation of the calculi of the submandibular glands may be related to the
      sialoadentitis and to the changes of saliva composition. Mineralization of the
      organic matrix may be one of the cause of calculus formation. By comparison of
      the glandular function with the pathology of the gland, it shows that the
      reduction of glandular function is associated with the severity of grandular
      inflammation. When function index is normal, grandular inflammation is in the
      Stage I or II, while it decreases or zero, grandular inflammation is in the Stage
      III or IV. Glandular function index may predict the severity of grandular
      inflammation.

PMID- 9592285
TI  - [Evaluation of ligature-induced periodontitis in minipig].
AB  - We evaluated the progressing period of ligature induced periodontitis in chinese
      minipig. Plaque index (PLI), bleeding index (BI), probing pocket depth (PD) and
      clinical attachment level (CAL) were measured in 3 minipigs. On weeks 4 and 8,
      there was a significant increase of the mean values of PD and CAL. After this
      active phase, there was no further destruction up to 20 weeks. Following ligature
      removed probing depths decreased in 3 weeks, but they did not restore to the
      baseline. It suggests that using ligature induced periodontitis model to evaluate
      the treatment therapy and medicine effect have to consider the self-healing of
      lesions, when a treatment trail is carried out in a model.

PMID- 9592286
TI  - [The role of P53 gene in the development of oral squamous cell carcinoma: study
      of P53 gene mutation by silver staining polymerase chain reaction-single strand
      conformation polymorphism].
AB  - It is widely accepted that the inactivation of P53 tumor suppressor gene is
      related to the tumorigenesis of many cancers. The study on P53 tumor suppressor
      gene has become a hotspot in molecular oncology. But until now, the reports on
      the research of the role of P53 gene in the tumorigenesis and prognosis of oral
      squamous cell carcinoma are scarce. So, two studies have been carried out. (1) A
      silver staining method of polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) analysis was established by detecting the mobility shifts
      of the DNA bands of the products of PCR of mutant P53 gene plasmid and the Sup F
      mutants which had been proved to have point mutation by DNA sequencing in shuttle
      vector plasmid pS 189 mutagenesised by N-methyl-N-nito-N-nitosoguanidine (MNNG).
      For the method is non-radiation with high sensitive, it has applicable value. (2)
      By silver staining PCR-SSCP system, tissues from normal oral mucoas membrane to
      metastatic oral squamous cell carcinoma (OSCC) were analyzed and the results
      showed that tissues from 53% oral precancerous lesions and 65% OSCC had abnormal
      SSCP bands and the abnormal frequency of metastatic cancers was higher than that
      of nonmetastatic ones. These suggest that P53 gene mutation plays some role on
      the process of initiation, development and metastasis of OSCC.

PMID- 9592287
TI  - [The effect of sampling repetition on gingival crevicular fluid and aspartate
      aminotransferase activity].
AB  - The purpose of the present investigation was to evaluate the influence on
      sampling repetition of aspartate aminotransferase (AST) level with 10-minute
      intervals. Tests based on the composition of gingival crevicular fluid (GCF) for
      detection of active periodontitis and GCF require the repetition of sampling. Two
      30-second samples of GCF were harvested with 10-minute intervals from 123 sites
      in 10 healthy subjects and 20 periodontitis patients. AST activity of the first
      samples in periodontitis subjects were approximately 7.8% greater than that of
      the second samples. The difference were not significant (P > 0.05). But in
      healthy subjects the difference were significant (P < 0.05). AST activity
      correlation positively with bleeding index (BI) and probing pocket depth (PD).

PMID- 9592288
TI  - [The characterization of Streptococcus mutans MT8148 and its glucosyltransferase
      deficient mutants].
AB  - The characterization of GTase-deficient mutants of S. mutans MT8148 was analysed
      to understand the possible virulence of GTase. In the presence of 1% sucrose,
      these mutants lost the ability to adhere to glass wall and the insoluble glucan
      synthesis was dramatically decreased. The GTase enzyme activity for insoluble
      glucan synthesis of these mutants was also decreased. Western blot using anti
      CAGTase polyclonal antibody and anti-GTFI or anti-GTFSI monoclonal antibody
      showed the lack of the corresponding GTase which further confirmed the mutation
      of specific GTase gene.

PMID- 9592289
TI  - [Effect of fibronectin on the synthesis of extracellular matrix proteins in
      periodontal ligament cells].
AB  - Immunofluorescence staining method and fluorescence spectrophotometry were used
      to study the synthesis of extracellular matrix proteins in periodontal ligament
      cells (PDL cells) when exogenous fibronectin (FN) existed. The results showed
      that the right amount of exogenous FN (0.044 mumol/l) could increase the amount
      of type I collagen and type III collagen in PDL cells (P < 0.01), inhibit the
      synthesis of FN itself (P < 0.01). It suggested that exogenous FN can effect the
      synthesis of extracellular matrix proteins so as to promote a new connective
      tissue attachment formation.

PMID- 9592290
TI  - [Histochemical study of lectin receptor and cell morphometric analysis on oral
      leukoplakias, epithelial dysplasia and squamous carcinoma].
AB  - The histochemical study of lectin receptor and the cell morphometric analysis
      were applied to cases to oral mucosal leukoplakias in order to find the
      differences between abnormal and normal cells in premalignant tissues. Results
      showed that the cell morphological change and glycosyl change of the cell surface
      in leukoplakias with severe epithelial dysplasia were similar to those of
      carcinoma, which suggests that the above methods may be used to differentiate the
      degree of the epithelial dysplasia of oral mucosal leukoplakias.

PMID- 9592291
TI  - [Disturbance syndrome of temporomandibular joint in cleft lip and palate patients
      with crossbite].
AB  - The function of temporor-mandibular joint in unilateral cleft lip and palate
      (UCLP) palients with crossibite was studied in this paper. 29 UCLP patients with
      crossbite were examined clinically and with Mandibular Kinesiography and X-ray.
      The results were as bellow (1) Insidence of TMJDS in UCLP patients with crossbite
      was 75.8%. (2) The condyle of 17.8% patients moved distally and 35.7% of patients
      moved distally asymmetry. (3) The distance of mandibular border movements in
      cleft patients were in normal range. We conclude that insidence of TMJDS in UCLP
      patients were high and we should take it into consideration in the orthodontic
      treatment.

PMID- 9592292
TI  - [Clinical observation of TMJDS treated with pivot splint].
AB  - The pivot splint was applied to 50 patients with temporomandibular joint
      dysfunction syndrome that included 30 patients of anterior disc displacement
      without reduction, 12 patients of anteriordisc displacement with partial
      reduction and 8 patients of upward condyle displacement. The mouth opening and
      joint space of the TMJ tomographies before and after treatment were measured for
      each case. The results indicated that treatment with pivot splint was very
      effective for the patients with downward diplacemenr of the condyle. As a result,
      among 50 patients, 36 patients were cured (72%) and 14 patients were improved
      (28%). The results of 3 years follow-up indicated that original symptoms of the
      patients had no recurrence.

PMID- 9592293
TI  - [A synthetical mouth study of 105 Uygur people above 100 years of age].
AB  - Oral examination was performed in 105 Uygur people aged 100 to 135 years. Among
      them there were 77 males and 28 females. Results were as follows: the teeth loss
      rate was 100.0%, edentulous rate 54.3%, dental caries 70.5%, periodontal disease
      52.4%, normal labial-buccal mucosa 65.7%, fissured tongue 74.3%, no smoking
      86.7%, no drinking 94.3%, and all of them had neither history of dental extration
      nor restoration. This study may provide data for investigating secret of human
      longevity.

PMID- 9592294
TI  - [The analysis of clinical dental crown of primary molar teeth].
AB  - For providing the anatomical data of primary molar teeth in China and using for
      the reference of clinical orthodontics, we measured and analysed the clinical
      crown of first and second primary molar teeth in 167 children of 4-6 years old
      finely. Each tooth was measured for 7 items with 9,228 in total. The heights of
      teeth crowns on buccal site were much taller than that on glossopalatal site
      except E. The mesial, distal and buccoglossal lenths were much longer on the
      enlarged part of crown than on the occlusive part. The mean values of symmetric
      teeth on both sites almost were of no difference. The mean values were not
      different in age groups (4.5 or 6 years old) either.

PMID- 9592295
TI  - [The application of the expert system in prosthedontics].
AB  - In this study, we developed an expert system for designing of frame work of
      Removable Partial Denture by the method of Artificial Intelligence. Both of Quick
      Basic and Tuber C language are used in this program. This system consider more
      other relative factors in removable partial denture designing except the amount
      and position of missing teeth. Base the idea of multy-layer knowledge we divide
      the process RPD designing into different layers according to their logical
      relationships. So, this system could imitate better the expert of prosthedontics
      to do the clinical examination, diagnosis, treatment plan and denture designing.
      There are 11 modules in this system totally. They are used to accomplish the case
      register, first visit examination, treatment plan, abutment examination, denture
      designing, biomechanic analysis of abutment, reference, explanation and etc. We
      used this system for 20 partial edentulous patients and compared the results with
      the designing plans of expert of prosthedontics, the rate of conformity is 83.6%.

PMID- 9592296
TI  - [Functional evaluation of the mitochondria from Warthin tumor].
AB  - The mitochondria were isolated from 8 surgical specimens of Warthin tumor of the
      parotid and the activity of the respiration was evaluated. The average
      respiratory control rate (RCR) of the mitochondria of the tumors (1.12 +/- 0.50)
      was lower than that of the normal mitochondria (2.10 +/- 0.75). The preliminary
      experiment showed a loosely coupled state of oxidative phosphorylation. It
      indicates that the hyperplasia of the mitochondria in the Warthin tumor results
      from the metabolic disturbance of the tumor and it is a compensation in the
      cellular level.

PMID- 9592297
TI  - [The application of regional excision of parotid gland in the treatment of
      Warthin tumors].
AB  - The regional excision of parotid gland (resection of the tumor with its
      surrounding glands) was applied in 54 cases with Warthin tumor. Its role was
      evaluated by follow-up study, iodine-starch test (Minor test), radionuclide
      scintigraphy, and comparison with superficial parotidectomy. The results showed
      that regional excision had the following advantages: shortening the time of
      operation, decreasing the injury of facial nerve, avoiding the facial deformity
      and Frey syndrome, and reserving the function of parotid glands. The theoretical
      basis, indications, and some considerable questions during the operation were
      discussed.

PMID- 9592298
TI  - [Study of HPV in oral squamous cell carcinoma].
AB  - In order to demonstrate the presence of human papillomavirus (HPV) in oral
      squamous cell carcinoma (OSCC), we detected HPV 16 and 18 type DNA in OSCC and
      normal mucosa (NOM) by polymerase chain reaction (PCR), then analysed the PCR
      products using southern blot hybridization. The study shows that the positive
      rates of HPV DNA were 47.8% (11/23) in OSCC, including HPV16 in 6 samples, HPV18
      in 3 samples and 16, 18 co-infection in 2 samples. In contrast, HPV16 DNA were
      found to be 20% (2/10) in NOM. The results suggest that HPV may play a role in
      carcinogenesis of OSCC.

PMID- 9592299
TI  - [Comparisons of three simple nutritional assessments applied to patients with
      oral and maxillofacial malignancies].
AB  - Combined subjective and objective nutritional assessment (SNA), concise
      nutritional assessment (CNA), general nutritional status score (GNS), and
      subjective global assessment of nutritional status (SGA) were applied to assess
      the nutritional status of 127 patients with oral and maxillofacial malignancies.
      On this base SNA was used as a standard nutritional assessment to compare the
      validities of CNA, GNS, and SGA. The results showed: 1) the total agreement rate
      of CNA (88.2%) was higher than that of GNS (78.0%) and SGA (78.7%); 2) the false
      positive rate (9.9%) and false negative rate (15.2%) of CNA was lower than that
      of GNS (17.3%, 30.4%) and SGA (14.8%, 32.6%); 3) the diagnosis index of CNA
      (74.9%) was significantly (P < 0.05) higher than that of GNS (52.3%) and SGA
      (52.6%); and 4) the nutritional parameters of CNA were measured by instruments
      with little man-made errors. These results indicate that CNA can be regarded as
      the best nutritional assessment for the patients in oral and maxillofacial
      surgery.

PMID- 9592300
TI  - [Role of hyaluronic acid in the temporomandibular joint and its therapeutic
      significance].

PMID- 9592301
TI  - [Problems in clinical trial of the eradication of Helicobacter pylori].

PMID- 9592302
TI  - [Problems in the diagnosis and treatment of Helicobacter pylori infection].

PMID- 9592303
TI  - [Omeprazole, clarithromycin and amoxicillin therapy for Helicobacter pylori
      infection].
AB  - The aim of this study is to determine the eradication rate in Helicobacter pylori
      (Hp) infection using omeprazole 20 mg twice daily, clarithromycin 500 mg twice
      daily and amoxicillin 1,000 mg twice daily for one or two weeks, in comparison
      with colloidal bismuth subcitrate 240 mg twice daily, amoxicillin 1,000 mg twice
      daily and metronidazole 400 mg twice daily for two weeks. 141 patients with Hp
      associated chronic gastritis or duodenal ulcer were randomly divided into 3
      groups. Group I (n = 48) treated with triple therapy of omeprazole,
      clarithromycin and amoxicillin for 1 week. Group II (n = 47) treated with the
      same drug and dosage for 2 weeks. Group III (n = 46) treated with triple therapy
      of colloidal bismuth subcitrate, amoxicillin and metronidazole for 2 weeks. The
      Hp status was determined by rapid urease test and histology of Warthin-Starry
      silver stain. The eradication rates of Group I, Group II and Group III were
      89.6%, 95.7% and 71.7% respectively. The difference between Group I and Group
      III, or Group II and Group III was significant. The difference of eradication
      rate between Group I and Group II was statistically insignificant. The frequency
      of side effects in Group III was higher than that in Group I or Group II.
      Although 21.1% of the patients in Group I and II experienced a metallic taste,
      none discontinued the medication. Our results show that triple therapy with
      omeprazole, clarithromycin and amoxicillin is an effective and well tolerated
      treatment for eradication of Hp infection and may be an alternative regimen to
      the old standard triple therapy.

PMID- 9592305
TI  - [The effects of teprenone on the ulcer healing rate and the quality of healing in
      the treatment of active gastric ulcers].
AB  - One hundred and six patients with active gastric ulcer proven by endoscopy were
      randomly allocated to receive cimetidine 800 mg at bedtime + teprenone 50 mg
      thrice daily; or cimetidine 800 mg at bedtime alone in a trial comparing the
      ulcer healing rate and the quality of healing at 4 or 8 weeks. At 4 weeks 72.4%
      (42/58) of those on cimetidine + teprenone and 52.1% (25/48) on cimetidine alone
      had ulcers healed in comparison of 93.1% (54/58) and 89.6% (43/48) respectively
      at 8 weeks. The difference was significant at 4 weeks, indicating the ulcer heal
      more rapidly in the combination therapy group. The stage S2 achievement rates
      were 34.5% (20/58) and 10.4% (5/48) at 4 weeks (P < 0.05), 50.0% (29/58) and
      20.8% (10/48) at 8 weeks (P < 0.05) respectively, indicating the quality of ulcer
      healing was much better in the combination therapy group. The gastric mucosal
      hexosamine levels increase significantly after treatment (17.79 +/- 2.00
      micrograms/mg) as compared to that before treatment (14.27 +/- 2.47
      micrograms/mg) in the combination therapy group, indicating that teprenone
      stimulates macromolecular glycoprotein synthesis in gastric mucosa. This is
      thought to be a significant factor in the healing process of gastric ulceration.
      CONCLUSION: It is reasonable to administer teprenone, an agent increasing mucosal
      resistance, concurrently with H2 blockers in the treatment of active gastric
      ulcers.

PMID- 9592304
TI  - [Clarithromycin combined short-term triple therapies for eradication of
      Helicobacter pylori infection].
AB  - In order to explore the optimal regimens for the eradication of Helicobacter
      pylori (Hp), eighty-eight patients with duodenal ulcer (DU) or non-ulcer
      dyspepsia and Hp infection, defined by culture and histology, received the one
      week triple therapy with clarithromycin (Cla), furazolidone (Fur) plus
      lansoprazole (Lan) or colloidal bismuth subcitrate (CBS). Twenty-eight patients
      entered the phase one preliminary study, randomized to receive the treatment of
      Cla 500 mg b.i.d and Fur 200 mg b.i.d plus either CBS 240 mg b.i.d (group I A) or
      Lan 30 mg b.i.d (group I B). Sixty patients entered the phase two main study,
      receiving the treatment of Cla 250 mg b.i.d and Fur 100 mg b.i.d plus either CBS
      240 mg b.i.d (group II A) or Lan 30 mg q.d (group II B). Five patients (2 in
      group I A, 2 in group I B, 1 in group II A) were withdrawn because of the side
      effects of the treatment, and two (in group II A) dropped out. The eradication
      rates of Hp in group I A, I B, II A, II B were 100.0% (12/12), 91.7% (11/12),
      92.6% (25/27) and 90.0% (27/30) respectively. There was no significant difference
      in the eradication rates of Hp between the treatment groups (P > 0.05). The
      primary resistant rate of Hp isolates to Cla was 7.5% (4/53) and no patient
      infected with the strain resistant to Cla succeeded in the eradication of Hp. The
      healing rates of DU were 94.4% (17/18) in group II A and 100.0% (18/18) in group
      II B (P > 0.05). The main side effects were nausea, vomiting and taste
      disturbance. Eighteen of the 28 (64.2%) patients in the phase one study had side
      effects with a rate significantly higher than that of 5.1% (3/58) in the phase
      two study (P < 0.001). CONCLUSIONS: (1) Both of the regimens used in the phase
      two study with low-dose, one week triple therapy are highly effective in the
      eradication of Hp infection and healing of DU, and are well tolerated. (2) The
      primary resistance of Hp strains to Cla is the principal factor of treatment
      failure in these two regimens.

PMID- 9592306
TI  - [The modulation of renal tubular epithelial cells treated with hypoxia on renal
      interstitial fibroblasts in coculture].
AB  - To clarify cell-cell interaction in the pathogenesis of renal tubulointerstitial
      nephritis (TIN), the effect of renal tubular epithelial cells (TEC) on renal
      interstitial peritubular fibroblasts (PTF) was examined in cell coculture system
      without direct contact. TEC and PTF were prepared from the kidney of BALB/C mice.
      Firstly, TEC were plated into intercup chambers of 24-well plates and incubated
      at 37 degrees C in a humidified 5% CO2 atmosphere for 72 hours. Then the cells
      were cultured in an incubator which was full of 95% N2 for 24 hours. Secondly,
      those intercups with hypoxia-treated TEC were floated on the wells of 24-well
      plates containing PTF which had been incubated for 24 hours. The TEC and the PTF
      were cocultured for another 48 hours. PTF were also cocultured with normal TEC as
      controls. The parameters of the cocultured PTF were measured as follows. (1) Cell
      proliferation examined by MTT incorporation method and the cell numbers were
      detected with total acid phosphatase activity. (2) Fibronectin (FN), laminin (LN)
      and collagen IV in the supernatants of coculture system were measured by ELISA
      method. (3) The distribution of ICAM-1 on the cell membrane of PTF was determined
      by laser confocal scanning microscopy. RESULTS: (1) The number of PTF cocultured
      with hypoxiatreated TEC was greater than that of controls (P < 0.01). (2) The
      level of FN and LN in the supernatants of the PTF cocultured with hypoxia-treated
      TEC was higher than that of the controls (P < 0.05). (3) The expression of ICAM-1
      on PTF cocultured with hypoxia-treated TEC was higher than that of controls (P <
      0.01). In conclusion the interaction of PTF and TEC may play a role in the
      pathogenesis of TIN.

PMID- 9592307
TI  - [Long-term prognosis of percutaneous transluminal coronary angioplasty in 229
      cases].
AB  - In order to approach long-term efficacy of percutaneous transluminal coronary
      angioplasty (PTCA) and the factors affecting its efficacy in Chinese patients,
      229 patients who underwent successful PTCA in this institution were followed by
      direct interview or letters. The rate of follow-up was 95% for the patients who
      should be followed. The period of follow-up was 0.5-8.4 (mean 2.3 +/- 1.8) years.
      Angina pectoris recurred in 76 (33.2%) of the patients. In 76% of the patients
      with recurrence, angina developed within 6 months after PTCA. Cox regression
      analysis revealed that the relative risk of recurrence of angina pectoris was
      increased among the patients with triple vessel disease and hypertension. During
      the period of follow-up, 2 (0.9%) patients died, 6 (2.6%) had non-fatal acute
      myocardial infarction, 4 (1.7%) had coronary artery bypass graft surgery, and 29
      (12.7%) had repeat PTCA. The cardiac event free survival rate calculated by
      Kaplan-Meier method was 84.8% at 1 year and 70.5% at 8 years. Cox regression
      analysis revealed that there were positive correlations between stenosis of
      lesions before PTCA and residual stenosis of LAD after PTCA and the relative
      risks of cardiac events. In conclusion, the long-term efficacy of PTCA in Chinese
      patients was good. We suggest that to decrease the residual stenosis of LAD
      during procedure could probably decrease the relative risk of cardiac events
      during follow-up.

PMID- 9592309
TI  - [Advances in the study on the etiology and pathogenesis of inflammatory bowel
      diseases].

PMID- 9592308
TI  - [A randomized clinical study of sulperazone versus tienam in the treatment of
      LRTIS].
AB  - The purpose of the clinical study is to evaluate the efficacy and safety of
      Sulperazone (SPZ) (sulbactam/cefoperazone) comparited with tienam in the
      treatment of lower resperiatory tract infections. A total of 73 patients enrolled
      in the study. 61 patients were evaluated for efficacy (SPZ 31, TIM 30) and 63
      patients were evaluated for safty (SPZ 31, TIM 32). Drugs were administered twice
      a day for 7-14 days, at a daily dose of either 2.0-4.0 g of sulperazone or 2.0
      4.0 g tienam. The overall clinical efficacy rates of sulperazone and tienam were
      93.5% and 93.3%, respectively. Total pathogens were isolated from 49 of 61
      patients prior to treatment. Over two-thirds of the isolates (37/48, 77.1%) were
      beta-lactammase producing strains. The bacterialogical clearance rate was 92.0%
      and 91.7% for both groups. The incidence of adverse drug reactions for SPZ and
      TIM were 3.2% and 10.0%, respectively. The susceptibility rates of the bacteria
      isolated to five drugs: sulperazone, tienam, ceftazidime, ceftriaxone and
      cefotaxime were 95.9%, 93.9%, 96.0%, 70.0%, and 80.0% respectively. The
      susceptibility rate of sulperazoene was significant.

PMID- 9592310
TI  - [Molecular basis of colorectal carcinomas].

PMID- 9592311
TI  - [Individualized treatment of patients with rheumatoid arthritis].

PMID- 9592312
TI  - [A study on the loss of heterozygosity at the APC/MCC and DCC genetic loci in
      colorectal cancers].
AB  - To evaluate the role of APC, MCC and DCC genes in the development and progression
      of colorectal cancers, loss of heterozygosity (LOH) at these genetic loci was
      investigated in 41 surgically resected specimens of colorectal cancer by using
      polymerase chain reaction (PCR) and restriction fragment length polymorphism
      (RFLP) analysis. LOH at APC or/and MCC was detected in 38.9% (14/38) of the
      informative cases; at the APC in 28.0% (7/25) and at MCC locus in 36.4% (8/22).
      LOH at DCC genetic locus was detected in 55.3% (21/38) of the informative cases.
      LOH rates DCC gene in the cancer specimens with lymphnode metastasis (80.0%) and
      in Dukes' stage III and IV (71.4%) were significantly higher than that in
      specimens without lymphnode metastasis (39.1%) and in Dukes' stage I and II
      (35.3%) (P < 0.05). Our results suggest that LOH at APC/MCC and DCC is the common
      genetic alterations in colorectal cancer and DCC genetic LOH assay may be useful
      in predicting the prognosis of patients with colorectal cancer.

PMID- 9592313
TI  - [A study on the changes of DCC and MCC genes in colorectal carcinoma and
      adenoma].
AB  - Both deleted in colorectal carcinoma (DCC) and mutated in colorectal carcinomas
      (MCC) genes are newly found tumour suppresser genes in colorectal carcinomas. In
      this study mutations of DCC gene and loss of heterozygosity (LOH) of MCC gene
      were detected with Southern blot and PCR methods respectively. The study
      consisted of 30 cases of colorectal adenoma (10 with mild, 10 with moderate and
      10 with severe dysplasia) and 33 cases of colorectal carcinomas (13 highly, 10
      moderately and 10 poorly differentiated, meanwhile 9 in Dukes A, 10 in B and 14
      in C stage). Their paired normal colorectal mucosa served as control. The results
      were as follows: mutation of DCC was not found in any specimen with normal mucosa
      or with adenoma of mild and moderate dysplaaia, while it was found in one if
      those with severe dysplasia. Mutation of DCC was, however, found in 7 of the 33
      specimens with carcinoma and there was a correlation between the positive rate
      and the differentiation or staging of the carcinoma. LOH of MCC was not found in
      normal mucosa, but it was found in 2/10, 3/10 and 4/10 of the adenoma specimens
      with mild, moderate and severe dysplasia respectively. 18/33 of the carcinoma
      specimens was found to have LOH of MCC and there was also a correlation between
      the positive rate and the differentiation or staging of the carcinoma. These
      results suggest that the frequency of multiple gene changes increase with poor
      differentiation and increased staging of colorectal carcinoma.

PMID- 9592314
TI  - [A study of the relevant factors of removal of common bile duct stones with
      endoscopic mechanical lithotripsy].
AB  - Endoscopic mechanical lithotripsy (EML) was attempted in 41 patients with common
      bile duct stones unable to be removed by endoscopic sphincterotomy. These
      patients had altogether 89 stones with stone size ranged from 5 to 30 mm (mean
      transverse diameter 16.6 +/- 6.0 mm and mean longitudinal diameter 20.0 +/- 7.1
      mm). 31 patients had 34 stones greater than or equal to 20 mm in transverse
      diameter. The overall stone removal rate was 97.6%. The rate of complete removal
      of the stone fragments with EML at one time was 78.6% (11/14) for large, 58.8%
      (10/17) for middle and 0 (0/5) for small incision of the sphincter. In patients
      with diameter of the distal common bile duct greater than or equal to 14 mm and
      less than 9 mm the rate was 83.3% and 30.8% respectively and the difference was
      of significance (P < 0.05). The rate of complete removal for using basket and
      balloon catheter was 6/10 and 4/9 separately and that for combined used of these
      two methods 83.3% (10/12). The rate of spontaneous passage of the stone (within
      one week) was 1/5. It is concluded that complete removal of the stone fragments
      was related mainly to the length of the incision, diameter of distal common bile
      duct and methods of removing stone fragments after the crush with lithotripsy
      basket; when the stone is large and there is the no space around the stone for
      lithotripsy basket manipulation, a large amount of diluted contrast material is
      injected into the bile duct so as to increase the space and facilitate the
      ensonaring of the stone with lithotripsy basket. Hard stones can not be crushed
      easily, so they constitute one of the reasons of failure.

PMID- 9592315
TI  - [The trend of changes in etiologic types of heart diseases in Shanghai from 1948
      to 1989].
AB  - Analysis of the data from 7188 cases seen in the 1980s two general hospitals in
      Shanghai and comparison of the data with those in the 1950s, 1960s and 1970s
      revealed that the percentage of heart diseases among the inpatients in medical
      wards increased in each decades, from 9.89%, 15.69% 20.91% to 23.54%
      respectively. The constituent ratios of different etiologic types of heart
      diseases changed. Coronary heart disease constituted the largest proportion, next
      in number was rheumatic heart disease and congenital heart disease was in the
      third place. The incidence of congenital heart diseases, myocarditis, cardiac
      dysrhythmias without organic heart diseases, cardiomyopathy and endocarditis
      increased and that of rheumatic heart disease, pulmonary heart disease and
      hypertensive heart disease apparently decreased, syphilitic heart disease was
      rarely encountered.

PMID- 9592316
TI  - [Characteristics and treatment of Staphylococcus aureus endocarditis].
AB  - In order to evaluate whether there were changes of the clinical features of
      Staphylococcus (Staph.) aureus endocarditis in recent years, the data of 21 cases
      of Staph. aureus endocarditis diagnosed from 1977 to 1994 were analyzed and
      compared with those of 11 cases of Staph. aureus endocarditis from 1957 to 1977.
      The results showed the following changes in recent years. The incidence of Staph.
      aureus endocarditis cases has been increasing. Cases of right-sided endocarditis
      increased in the recent two decades and this increase was related to intravenous
      drug abuse and increased use of vascular intervention. Right-sided endocarditis
      was different from left-sided endocarditis in their risk factors, underlying
      heart diseases, clinical manifestations and prognosis. The clinical
      manifestations of ventricular-wall endocarditis were atypical and it could be
      definitely diagnosed only with echocardiogram. Complications of Staph. aureus
      endocarditis became more common and serious, in recent decades but hospital
      mortality decreased markedly due to effective antibiotic management. The authors
      believe that sound knowledge of Staph. aureus endocarditis is essential for the
      proper diagnosis and treatment of Staph. aureus endocarditis.

PMID- 9592317
TI  - [A study on the pathogenetic role of the viral structural proteins of hemorrhagic
      fever with renal syndrome].
AB  - In order to clarify the pathogenesis of hemorrhagic fever with renal syndrome
      (HFRS), we detected HFRS virus structural proteins expressed in perepheral blood
      mononuclear cells (PBMC) by using immunohistochemical technique. Meanwhile we
      also determined plasma endothelin (ET), substance P (SP) and some sensitive
      markers of renal function with radioimmunoassay. The result showed that in HFRS
      patients, from the day of admission up to the thirteenth day of illness, the
      antigens of HFRS virus membrane protein (MP) and nucleocapsid (NP) could
      simultaneously be found in PBMC, though their expressive degree gradually
      decreased when the condition of the patients became better. Based on the external
      appearance and nucleus pattern of PBMC we recognized the MP and NP positive cells
      were mainly monocytes among which only a few presented faint IgM and C3 stain. On
      admission there was difference in expressive intensity between MP and NP. The MP
      expressive intensity was in parallel with plasma ET/SP ratio, the general
      condition and the severity of renal damage. These data suggest that HFRS virus
      can invade PBMC, replicate in them, and express their structural proteins. MP may
      be related with the pathogenesis of HFRS virus and the increase of plasma ET/SP
      ratio may be an important factor aggravating kidney injury.

PMID- 9592318
TI  - [Endothelin-1 receptors of the normal adrenal gland and adrenal tumors in human].
AB  - Endothelin-1 (ET-1) receptors of normal adrenal gland (ADR, 6 cases), aldosterone
      producing adenoma (APA, 5 cases), idiopathic hyperaldosteronism (IHA, 4 cases)
      and pheochromocytoma (PHE, 6 cases) in human were measured by radioligand binding
      assay (RBA) of receptors. Binding studies using 125I-ET-1 as a radio ligand
      showed the presence of a single class of high-affinity binding sites for ET-1 in
      all of the above tissues. The values of dissociation constant (Kd) of ET-1 for
      its receptor were similar in ADR, APA and IHA (28.3 +/- 2.5, 27.9 +/- 6.1, 27.7
      +/- 1.9 pmol/L, respectively), but the maximal binding capacity (Bmax) of ET
      receptor tended to be lower in APA tissue (107.2 +/- 13.2 fmol/mg protein) in
      comparison with ADR (P < 0.01) and IHA (P < 0.05, 274.9 +/- 40.8, 247.0 +/- 19.8
      fmol/mg protein, respectively). Both the Kd (50.8 +/- 5.1 pmol/L) and Bmax (675.3
      +/- 93.7 fmol/mg protein) in PHE were higher than those in ADR (P < 0.01), APA (P
      < 0.01) or IHA (P < 0.05 for Kd, P < 0.01 for Bmax). Our data may suggest that
      there is the down-regulation for ET-1 receptor in APA and support the concept of
      an important role of ET-1 in the paracrine-autocrine regulation of aldosterone
      and catecholamine secretion in the adrenal and adrenal tumors.

PMID- 9592319
TI  - [Observation on therapeutic effect of megestrol acetate on patients with chronic
      obstructive pulmonary disease at remission stage].
AB  - It has been reported that malnutrition is common in stable chronic obstructive
      pulmonary disease (COPD) patients. In order to observe the effects of Megestrol
      Acetate (MA) on nutritional status, respiratory muscle strength and immunological
      parameters in stable COPD patients, 31 stable COPD patients were divided into two
      groups at random--a treatment group of 16 cases and a control group of 15 cases.
      Before and after treatment all parameters were recorded, including food and
      energy intake, body weight, triceps skinfolds (TSF), pre-albumin, transferrin,
      albumin. Lung function, respiratory muscle and handgrip strength were examined
      and immunological parameters also determined. After taking MA 160 mg/day orally
      for two weeks, the treatment group got benefits as follows: heat energy and
      protein intake increased fro 6977.9 +/- 1136 kJ/d and 44.65 +/- 13.75 g/d to
      9854.0 +/- 2355.3 kJ/d and 84.80 +/- 20.23 g/d respectively. With the increase of
      daily energy and protein intake, body weight increased from 48.27 +/- 8.61kg to
      50.34 +/- 8.76 kg, TSF from 11.75 +/- 4.50 mm to 15.06 +/- 4.73 mm, serum pre
      albumin from 306.6 +/- 33.7 mg/L to 332.6 +/- 1 mg/L, transferrin from 3.09 +/-
      0.21 g/L to 3.46 +/- 0.32 g/L, albumin from 38.00 +/- 1.73 g/L to 42.64 +/- 3.36
      g/L, MIP from 4.77 +/- 2.14 kPa (1 kPa = 7.5 mmHg) to 6.31 +/- 2.87 kPa, MEP from
      6.21 +/- 2.90 kPa to 7.20 +/- 3.67 kPa and 6 minutes walking distance from 280.2
      +/- 76.4 m to 370.6 +/- 81.5 m. Handgrip strength also improved. Blood lymphocyte
      transformation rate elevated too. (The changes of all these parameters indicated
      above were statistically significant, P < 0.01). However, parameters of lung
      function, blood gas analysis, serum immunoglobulin and complement 3 did not
      change significantly. In 15 control patients all the parameters did not change
      significantly. There were few side effects; only one case complained of nausea
      and vomiting. It was shown that MA can stimulate appetite and increase
      dietintake, improve nutritional status, elevate respiratory muscle strength, and
      enhance immunity. MA is a safe and effective drug which exerts a beneficial
      influence on stable COPD.

PMID- 9592320
TI  - [The pathogenetic influence of tubulointerstitial lesions on the glomerular
      function in IGg nephropathy: a study of 90 cases].
AB  - To evaluate the significance of tubulointerstitial lesions in IgA nephropathy,
      clinicopathological studies were performed on 90 cases of this disease. The
      degree of tubulointerstitial lesions was assessed semiquantitatively by light
      microscopic observation. The relation between glomerular filtration rate (GFR)
      and multiple clinicopathological factors was analysed by correlation analysis and
      logistic regression. The results showed that the degree of renal impairment at
      the time of biopsy was clearly correlated with and largely determined by the
      tubulointerstitial lesions, in particular the density of interstitial
      infiltration by lymphocytes and monocytes/macrophages. It is indicated that
      tubulointerstitial lesions play an important role in the pathogenesis of renal
      impairment in IgA nephropathy.

PMID- 9592321
TI  - [Subclinical hepatic encephalopathy].

PMID- 9592322
TI  - [Appeal to prevent the spread of AIDS].

PMID- 9592323
TI  - [Insulin-resistant syndrome and tumor necrosis factors].

PMID- 9592324
TI  - [A prospective study on post-transfusion hepatitis C].
AB  - A cooperative prospective study on the clinical epidemiology of post-transfusion
      hepatitis C virus (HCV) infection was carried out from April 1993 to November
      1994 in four medical schools in China, namely, Peking Union Medical College
      (PUMC), Western China Medical University (WCMU), Shanghai Medical University
      (SMU) and Beijing Medical University (BMU). A screen test on anti-HCV was done
      for the healthy donors of four groups. Anti-HCV positive rate was found to be
      14.49% in professional blood donors, 5.60% in rural donors and 0.42% in urban
      volunteer donors. The positive rate of anti-HCV in blood recipients followed more
      than three months after transfusion was quite different in the four institutes,
      being 15.34% (14/91) in PUMC, 24.59% (15/61) in WCMU, 13.18% (12/91) in SMU and
      1.53% (1/65) in BMU. During the same period post-transfusion hepatitis B virus
      infection rate decreased as compared with that in the past. It is concluded that
      the screen test on anti-HCV in blood donors can not completely rule out post
      transfusion HCV infection.

PMID- 9592325
TI  - [A clinical study in the treatment of acute bacterial infections with
      fleroxacin].
AB  - The purpose of this clinical trial is to evaluate the efficacy and safety of
      fleroxacin and to compare with those of lomefloxacin. A randomized controlled
      study was carried out to treat sixty patients with urinary tract and respiratory
      tract bacterial infections, thirty in each group with one of the two drugs, and
      fifty cases were treated with fleroxacin in an open trial. Altogether there were
      one hundred and ten cases. Both fleroxacin and lomefloxacin were given orally,
      the dosage was 200 mg every 12 hours or 400 mg every 24 hours for 7-14 days. The
      clinical efficacy rate was 93.3%; the culturing rate in the fleroxacin group was
      83.3%; the bacterial clearance rate was 92.3%, the incidence of adverse reactions
      was 9.4%, while in the lomefloxacin group they were 90.0%, 80.0%, 87.5% and 6.7%
      respectively, with no statistically significant difference between the two groups
      (P > 0.05). In the open and randomized trials, fleroxacin cured eighty cases of
      bacterial infections, the overall clinical efficacy rate was 90.0%, the culturing
      rate in the flero-xacin group was 83.8%, the bacterial clearance rate was 88.2%
      and the incidence of adverse reactions was 9.6%. It is shown that fleroxacin is
      an antibiotic of broad-spectrum, high efficacy and safety.

PMID- 9592326
TI  - [The evaluation of cefmetazole in clinical use. The study group of cefmetazole in
      clinical use].
AB  - To study the clinical effect of cefmetazole (CMZ), we treated with CMZ 1,926
      patients with various infections involving the respiratory tract,
      gastrointestinal tract, liver and biliary tract, skin and soft tissue and others.
      The marked effect rate was 56.5%, and the effect rate 33.7%. The sensitivity test
      of CMZ was also performed in vitro. Staphylococcus aureus, streptococcus,
      staphylococcus epidermis, E. coli, S. typhi, B. salmonella, B. shigella, B.
      Klebsiella pneumoniae, B. proteus, etc. were sensitive to CMZ. Injecting CMZ can
      prevent the infection of operation. The study of the adverse reaction of CMZ
      showed, an adverse reaction rate of 4.2% (the gastrointestinal tract, allergy,
      kidney and nervous system). These results suggested that CMZ is an antibiotic of
      broad spectrum, high efficacy and low toxicity. It is effective in treating
      sensitive bacterial infection, unknown pathogenic infection and mixed bacterial
      infection, and preventing infection in surgery.

PMID- 9592327
TI  - [An investigation on the changes of coagulation and fibrinolytic system in
      intensive infection with multiple organs failure].
AB  - An investigation was made for the significance of changes of coagulation and
      fibronolytic system in intensive infection with multiple system organ failure
      (MSOF). In 68 cases with various degrees of infection, hematological
      examinations, including estimation of PT, APTT, Fg, Fn and D-Dimer, activation of
      coagulation factor II, VII, X, XII (F II, F VII, F X, F XII), AT-III, PLG,
      alpha(2)-AP, t-PA and count of platelets were carried out. The results were as
      follows: In intensive infection with MSOF, PT and APTT increased significantly;
      activity of F II, F VII, F X and F XII decreased significantly platelet count and
      Fn decreased markedly; concentration of Fg and D-Dimer increased significantly;
      activity of PAI increased markedly; activity of t-PA and alpha(2)-AP decreased
      slightly. The incidence of MSOF not combined with DIC was 38.5%, but that
      combined with DIC was 79.7% (P < 0.01). It is suggested that DIC is the most
      important factor in the disorder of coagulation and fibrinolytic system. It play
      an important role in the pathogenesis and development of MSOF.

PMID- 9592329
TI  - [A study on glycosylated high density lipoprotein and its binding to receptors in
      human lung fibroblasts in diabetic patients].
AB  - In order to know the glycosylation of high density lipoprotein (HDL) and its
      specific binding to human lung fibroblasts (HLF) receptors in diabetic patients,
      the glycosyflation of HDL in diabetic group I (HbAlc < 7.6%) and II (HNbAlc >
      9.6%) and a control group were measured with fluorimetry. The hydrazides in
      carbonyl radical of HDL in the three groups were conjugated with horadish
      peroxidase (HRP). The specific binding of HDL-HRP to HLF receptors was measured
      with enzyme linked immunoreceptor assay. The results showed that the glycosylated
      amount of HDl in group I, II and the control group was 39.26 +/- 8.10, 72.96 +/-
      6.40 and 20.40 +/- 1.10 glycogroups/HDL respectively. The surface specific
      binding of HDL-HRP to HLF receptors in medium with high cholesterol was
      significantly greater than that in medium without cholesterol (P < 0.01). The
      surface specific binding of HDL-HRP to HLF receptors in group I and II was
      significantly lower than that in the control group (P < 0.01) and that in group
      II was significantly lower than in group I (P < 0.01). The results indicate
      glycosylated HDL in diabetic patients is increased but its specific binding to
      HLF receptors is decreased as compared with that in control subjects.

PMID- 9592328
TI  - [A study of insulin sensitivity and its related factors in patients with non
      insulin dependent diabetes mellitus and impaired glucose tolerance].
AB  - In order to evaluate insulin sensitivity and its related factors in abnormal
      glucose tolerance, 572 cases of non-insulin dependent diabetes mellitus (NIDDM),
      647 cases of impaired glucose tolerance (IGT) and 543 normal controls were
      studied. The results showed that fasting insulin levels (FIns) and the prevalence
      of hyperinsulinemia were higher in NIDDM than that in IGT and higher in IGT than
      that in normal controls (P < 0.01). Insulin sensitivity index (ISI) [-ln(FInx x
      fasting blood glucose)] ranked from high to low in the order of normal controls,
      IGT subjects, newly-diagnosed NIDDM patients and patients with known NIDDM (P <
      0.01). In each group ISI was smaller in obese subjects or patients than in non
      obese ones. Mono-factor analysis demonstrated that ISI in each group was
      negatively related to body mass index (BMI) and positively related to high
      density lipoprotein (HDL)-cholesterol. ISI in NIDDM and IGT group was negatively
      related to blood pressure. Multiple analysis showed that the ISI had
      significantly negative correlation with BMI and some correlation with blood
      pressure and blood lipids. In conclusion, the patients with abnormal glucose
      tolerance had hyperinsulinemia and insulin resistance. ISI was related to some
      risk factors of vascular diseases.

PMID- 9592330
TI  - [Study on small intestinal lumenal and membrane flora of 30 healthy Chinese].
AB  - Lumenal and membrane flora were investigated using ileum and jejunum samples
      obtained through endoscopy. 10 kinds of representative anaerobic or aerobic
      bacteria were cultured for quantitative and qualitative analysis. The result
      showed there were significant differences between lumenal and membrane flora on
      Clostridium of ileum, Lactobacillus and Bacillus bifudus in jejunum (P < 0.05).
      Enterococci were not found in all of these 30 patients. In jenumum, E. Coli was
      found in 53.3% (16/30) of lumenal flora and 33.3% (10/30) of membrane flora,
      Bacteroides were found in 40.0% (12/30) of lumenal flora and 33.3% (10/30) of
      membrane flora respectively.

PMID- 9592331
TI  - [Detection of severity of coronary stenosis by quantitative myocardial tomography
      with Tc-99m-MIBI at rest].
AB  - To evaluate the role of myocardial tomography with Tc-99m-MIBI (MB) in detecting
      abnormal coronary arteries, 34 patients with myocardial infarction underwent
      resting quantitative SPEC with MB and coronary arteriography within one month.
      When segmental MB uptake was < 560% of the left ventricular peak activity, there
      was 88% probability that a totally occluded or severely stenosed coronary artery
      (stenosis > 90%) was involved. There was 82% probability of finding no
      significant stenosis of coronary arteries in the normal myocardial segments. In
      the myocardial segments supplied by occluded coronary arteries, there was
      significantly higher MB uptake in the segments with good collateral circulation
      as compared with those subtended by a vessel totally occluded with poor
      collateral circulation (P < 0.05). The sensitivity and specificity of detecting
      abnormal coronary artery by quantitative analysis of myocardial tomography was
      87% and 90% respectively. It is suggested that quantitative analysis of
      myocardial tomography with MB can differentiate between myocardial segments
      supplied by severely stenosed and normal coronary artery and evaluate the
      existence of collateral circulation.

PMID- 9592332
TI  - [Is mixed connective tissue disease a distinct rheumatic disease].
AB  - Mixed connective tissue disease (MCTD) as a distinct clinical entity is still
      controversial. To address the issue, the authors observed the evolution of 50
      patients diagnosed as MCTD at our clinic, evaluated the reliability of three
      different diagnostic criteria proposed by Sharp, Alarcon-Segovia and Kasukawa
      respectively and performed HLA-A, -B and -DR antigen typing in 38 of the
      patients. The results showed that: (1) 13 (26.9%) of the 50 MCTD patients
      subsequently developed other connective tissue disease (OCTD) including 7
      systemic lupus erythematosus (SLE), and 6 progressive systemic scleroderma (PSS).
      (2) among 23 of the MCTD patients fulfilling Sharp's criteria, 1 (4.3%) developed
      PSS, but among 23 of the patients fulfilling Kasukawa's, not Sharp's, 7 (30.4%)
      developed OCTD and among 27 of the patients fulfilling Alarcon-Segovia's, not
      Sharp's, 12 (44.4%) developed OCTD. (3) in the frequencies of DR, and DR5, there
      were significant differences between patients fulfilling Sharp's (60.9%, 56.5%)
      and the normal controls (24.3%, P < 0.005, RR = 4.7 and 21.4%, P < 0.005, RR =
      4.6%), but no significant differences between the patients not fulfilling Sharp's
      and normal controls (P > 0.05). We concluded that: (1) MCTD is a distinct
      rheumatic disease. (2) Sharp's criteria is the most reliable for diagnosis of
      MCTD.

PMID- 9592333
TI  - [Antineutrophil cytoplasm autoantibodies and diseases].

PMID- 9592334
TI  - [Chronic cor pulmonale: progress in the prevention, treatment and research].

PMID- 9592336
TI  - [Can respiratory acidosis and respiratory alkalosis occur simultaneously?].

PMID- 9592335
TI  - [Typing and diagnosis of mixed acid-base disorders].

PMID- 9592337
TI  - [The role of human leukocyte antigen in susceptibility and clinical
      manifestations of sarcoidosis].
AB  - To investigate the association of human leukocyte antigen (HLA) with
      susceptibility and clinical manifestations of sarcoidosis. Fifty-five patients
      with sarcoidosis were studied by using allele group specific polymerase chain
      reaction technique (PCR). Our data show that: (1) the gene frequency of HLA-DR5
      is significantly increased in patients with sarcoidosis, but that of HLA-DR7
      decreased. (2) Gene frequencies of HLA-DR9 and HLA-DR5 are relatively increased
      in male patients and in patients with stage I and stage IIa, respectively. The
      results suggest that HLA-DR gene might contribute to the susceptibility as well
      as to the difference of clinical manifestations in sarcoidosis.

PMID- 9592338
TI  - [Changes on level and expression of endothelin-1 in the lungs of rats with
      hypoxic pulmonary hypertension].
AB  - The aim of the present study was to determine whether mRNA for endothelin-1 (ET
      1) was present and changed in the lungs of rats exposed to chronic hypoxia, cRNA
      probes for rat ET-1 and c-fos were labelled by in vitro transcription with
      digoxigenin-UTP for in situ hybridization. Endothelin-1 like immunoactivity (ET-1
      LI) in plasma as well as in lung homogenate was measured by radio-immunoassay.
      The results showed that the vascular endothelia cells of pulmonary artelics and
      the bronchiolar epithelial cells were strongly positive for the ET-1 probe. The
      perivascular and peribronchiolar smooth muscle were positive for the c-fos probe
      primarily. Whereas, there were little expression of ET-1 and c-fos in the rat
      lungs in controls. There were significant increase of ET-1-LI levels in rats
      exposed to hypoxia for 3 weeks, the concentration in venous samples was 3.85 +/-
      1.52ng/L (P < 0.05 as compared with the control groups), in arterial sample was
      4.72 +/- 1.66ng/L (P < 0.05) and in lung tissue was 2.06 +/- 0.68ng/g wet lung
      weight (P < 0.05). It is suggested that chronic hypoxia elevated the mean
      pulmonary arterial pressure, caused vessel remodelling and right ventricular
      hypertrophy. These changes were accompanied by an increase of ET-1 in plasma and
      lung homogenate. The expression and production of ET-1 were localized to
      endothelium and airway epithelium in the lungs.

PMID- 9592339
TI  - [Detection of p53 gene mutation in bronchial biopsy samples from lung cancer
      patients with polymerase chain reaction-single strand conformation polymorphism
      silver staining method].
AB  - In order to diagnose lung cancer at gene level, bronchial biopsy specimens from
      lung cancer patients, who were diagnosed by pathologic method using biopsy
      specimens from the same site, were used for detection of p53 gene mutation by
      polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP)
      silver staining method. 15 of 25 (60%) specimens were found to be positive. In 10
      small cell lung cancer specimens, 7 were positive; in 15 non-small lung cancer
      specimens, 8 were positive. These results coincided with those of other reports
      using surgical specimens and sequencing method. Clinical analysis showed no
      correlation between SSCP positivity and the patients' clinical data such as age,
      sex, smoking habit, stage of tumor at the time of diagnosis. It is concluded that
      a small piece of bronchial biopsy specimen could be used to detect p53 gene
      mutation instead of surgical specimens and this method might be used as an
      adjunct to cancer screening or for a gene diagnosis prior to gene therapy. In
      comparison with the routine radionuclide labelled method, silver staining method
      has the advantage of being simple, quick, economic, safe and convenient for
      clinical use.

PMID- 9592340
TI  - [The detection of the antibodies of human cytomegalovirus in the sera of patients
      with coronary heart disease].
AB  - To explore the relationship between human cytomegalovirus infection and
      atherosclerosis, we assayed the antibodies of human cytomegalovirus in the sera
      of 106 patients with coronary heart disease and 80 healthy people by indirect
      ELISA technique. The results showed that the positive rate of antibodies of HCMV
      IgG, HCMV IgM and HCMV IgA (95.3%, 12.3%, 13.2% respectively) is significantly
      higher than that in healthy people (85.0%, 2.5%, 3.8% respectively). Our findings
      indicated that HCMV infection is related to coronary heart disease. We consider
      that HCMV may be an etiological factor for human atherosclerosis. The periodical
      activation of latent HCMV may play a role in atherogenesis.

PMID- 9592342
TI  - [Armillifer agkistrodontis disease: report of case].
AB  - A case of Armillifer agkistrodontis disease was reported. Armillifer
      agkistrodontis is a species of the Armillifer genus of the Linguatulida order and
      parasitizing agkistrodon acutus. According to literature reviewed, there has been
      no report of this disease caused by infection of Armillifer agkistrodontis in
      human being prior to this case all over the world. The clinical features of this
      disease are long-term high fever, abdominal pain, diarrhea, mild anemia,
      hepatosplenomegaly, eosinophilia in bone marrow and blood and multiple polyps in
      the whole colon. The pathologic features of the liver biopsy was degeneration and
      necrosis of hepatocytes and obvious infiltration of eosinophils. This disease
      should be differentiated from several other diseases which can also cause
      hepatomegaly, long-term high fever, abdominal pain and diarrhea. Mebendazole is
      an effective medication for this disease, but the long term effect of
      praziquantel is not certain. It is necessary to make further studies on the
      epidemiology, etiology, pathology, natural history, clinical features, diagnosis,
      differential diagnosis and therapy of this disease.

PMID- 9592341
TI  - [Study of nitric oxide synthases, nitric oxide and tumor necrosis factor in
      different types of ascites].
AB  - The purpose of this study was to elucidate the clinical significance of nitric
      oxide synthases (NOS), nitric oxide (NO) and tumor necrosis factor (TNF) in
      different types of ascites. NOS, NO and TNF in ascitic transudates of 21 patients
      with liver cirrhosis, ascitic exudate of 32 patients with liver cirrhosis and
      carcinogenesic ascites of 19 patients were measured by Griess, ELISA and
      colorimetric methods. Compares to the value in ascitic transudate of 21 patients
      with liver cirrhosis, NOS (7.32 +/- 3.13 nmol.min-1.g-1), NO (15.4 +/- 7.6
      mumol/L) and TNF (331.7 +/- 121.2 mumol/L) in ascitic exudate of 32 patients with
      liver cirrhosis were significantly higher (P < 0.01). The NO (10.7 +/- 3.2
      mumol/L) and TNF (185.6 +/- 84.1 mumol/L) in carcinogenesic ascites of 19
      patients were between those in ascitic exudates and those in ascitic transudates
      of patients with liver cirrhosis (P < 0.05 or 0.01). The NOS activity was highest
      in carcinogenesic ascites. The decrease of 24h urine volume in patients with
      cirrhosis was relative to the increase of NO level in ascites. Those suggested
      that measurements of NOS, NO and TNF in ascites are helpful in differential
      diagnosis of ascites. The separation between NO level and NOS activity in ascites
      indicates that the ascites is carcinogenesis.

PMID- 9592343
TI  - [Fas expression and DNA impairment of hepatocyte in chronic hepatitis B].
AB  - To elucidate the role of apoptosis in the pathological lesion of hepatitis B
      virus (HBV) infection, biopsied liver tissue specimens of 38 patients with
      chronic hepatitis B of varying severity were investigated with in situ
      immunohistochemistry and TUNEL test. Apoptotic hepatocytes were found to be rare,
      while the nuclei of many cells were positively stained with TUNEL, suggesting 3'
      OH ends generated as the DNA was impaired. Of the 17 cases with mild lesion or
      without piecemeal necrosis, 14 were negative or weakly positive with both Fas and
      TUNEL test. Of the 7 cases with piecemeal and bridging necrosis, none was
      strongly positive. In the 14 cases with active hepatitis and early cirrhosis,
      strongly positive results with Fas were found in 9 and with TUNEL in 3
      respectively. It is suggested that the cytotoxic T lymphocyte (CTL)-Fas-apoptosis
      mechanism was involved in the hepatocyte death of hepatitis B as well. The Fas
      expression, DNA damage and apoptotic cells distributed mostly in the piecemeal
      necrosis region, and the ballooning and the necrotic hepatocytes were also
      clustering in this region. As both the apoptosis and necrosis are mediated by
      CTL, they are closely related: while transducted by different ways, they occurred
      independently.

PMID- 9592344
TI  - [Detection of serum HCV RNA and HBV DNA in patients on hemodialysis].
AB  - In order to assess the relationship between seropositivity and potential
      infectivity caused by hepatitis C virus (HCV) and hepatitis B virus (HBV) in
      patients undergoing maintenance hemodialysis, 22 patients in our dialysis unit
      were evaluated by using nested RT-PCR to detect serum HCV RNA, ELISA to detect
      serum anti-HCV antibodies, dot blot to detect serum HBV DNA and RIA to detect HBV
      serum markers. Twenty-seven percent of the patients (6 of 22) was anti-HCV
      positive. Of the 6 anti-HCV-positive patients, HCV RNA was detected in 3 (33%)
      patients. Among the anti-HCV-negative patients, HCV RNA was detected in one (6%)
      of the 16 patients. Fourteen percent (3 of 22) was HBV DNA-positive. Of the 3 HBV
      DNA-positive patients, HBeAG was detected in all of them. Among the nineteen HBV
      DNA-negative patients, no HBeAg was detected, but anti-HBc was detected in 12
      (63%) of the 19 patients. Five of the seven patients with HCV infection (HCV-Ab
      and/or HCV RNA-positive) had evidence of additional present or past hepatitis B
      virus infection (4 of the 5 patients were anti-HBc-positive and one of the 5 was
      HBV DNA, HBeAg, HBsAg, and anti-HBc-positive). However, no HCV RNA and HBV DNA
      were found to coexist in the same patient in this study. These data indicate that
      many patients on hemodialysis have hepatitis C or B viremia and more attention
      should be paid to this problem.

PMID- 9592345
TI  - [Pathogenesis of Guillain-Barre syndrome and its relation with Campylobacter
      jejuni].

PMID- 9592346
TI  - [Role of renal tubulointerstitial damage in the progress of chronic renal
      failure].

PMID- 9592347
TI  - [Caution against secondary cancer induced by antitumor chemotherapy].

PMID- 9592348
TI  - [Reappraisal of granulocyte transfusion].

PMID- 9592349
TI  - [Thrombosis, hemostasis and clinical medicine].

PMID- 9592350
TI  - [Detection of immunoglobulin heavy chain (IgH) gene rearrangement in ANLL by
      polymerase chain reaction amplification and Southern blot].
AB  - Immunoglobulin heavy chain (IgH) gene rearrangement serves as a marker of
      clonality in B lymphoproliferative malignancies. In order to study the IgH
      rearranged gene in acute nonlymphoblastic leukemia (ANLL) patients we combine
      polymerase chain reaction (PCR) with Southern blot to detect 41 ANLL patients and
      7 of them (17.1%) were found to have IgH rearrangement by PCR amplification. All
      these 7 positive cases were confirmed by Southern blot. The sensitivity of this
      method was 10(-4)-10(-5) level. In 12 patients with complete remission, 3 (25.0%)
      were found to have IgH rearranged gene. All these 3 cases had clinical relapse
      within 6 months. Our results show that IgH rearrangement not only may occur in
      lymphoblastic leukemia of B lineage, but also can be found in ANLL. The mechanism
      may be that in some ANLL patients, the leukemic transforming event might involve
      stem cells capable of both B cell and myeloid differentiation or ANLL might
      differentiate along different lineage with predominant appearance of one or the
      other subclone in the course of the disease.

PMID- 9592351
TI  - [Detection of multidrug resistance in patients with leukemia by using flow
      cytometry and RNA in situ hybridization].
AB  - Multidrug resistance (MDR) in leukemia and the reversal of MDR by cyclosporin A
      (CsA) in vitro have been studied through intracellular accumulation of
      daunorubicin (DNR) in leukemic myeloblasts. The study was carried out with real
      time flow cytometry and relative expression levels of MDR, which is estimated by
      RNA in situ hybridization in 26 patients suffering from leukemia. The change of
      intracellular DNR accumulation in vitro after adding CsA was also analyzed. The
      results showed that intracellular DNR accumulation in newly diagnosed and treated
      patients (MDR1 negative) with remission increased significantly than that in
      refractory and relapsing patients (P < 0.01). Good reversal effect was obtained
      in refractory patients and MDR1 positive relapsing patients by adding CsA (P <
      0.01). It is suggested that MDR detection by the two above-mentioned methods
      could help to project the chemotherapy schedule clinically, CsA had obvious
      reversal effect on the drug-resistant leukemic cells in vitro.

PMID- 9592352
TI  - [Dynamic analysis of cell surface markers in acute leukemias unclassified with
      immunologic criteria].
AB  - In order to study the cell origin of acute leukemia with lack of lineage specific
      antigen expression, the dynamic change of cell surface markers in 25 patients of
      acute leukemia unclassified with immunologic criteria were analysed by using
      APAAP immunoenzymatic method with monoclonal antibodies after chemotherapy or
      relapse. The results showed that 5 patients, whose leukemic cells expressed only
      CD38 antigen in the first visit, expressed T cell differentiated antigen after
      chemotherapy or relapse. 4 patients, who expressed B cell specific markers after
      chemotherapy or relapse, all expressed only CD9 antigen in the first visit. 4 of
      the 6 patients who expressed only HLA-DR antigen were found to have B cell
      markers on their leukemic cells surface after chemotherapy or relapse. One
      patient expressed B cell surface markers after chemotherapy and another expressed
      T cell surface markers after relapse, both of them expressed CD38 and HLA-DR
      antigens in the first visit. In 4 other patients whose leukemic cells were
      lacking of in any cell differentiated antigen expressing, one expressed B cell
      markers and another expressed T cell markers after chemotherapy. The change of
      cell surface markers showed the evolution and progression of leukemic cell clone.
      Dynamic study is useful to distinguish the cell origin of leukemia.

PMID- 9592353
TI  - [An investigation of a family tree with congenital deficiency in coagulation
      factor XIII].
AB  - In order to study the hereditary trait of a 20-year-old girl with congenital
      deficiency of coagulation factor XIII and her family tree, the following
      laboratory tests were done for the propositus and her family members: clot
      solubility test in 5 mol/L urea, estimation of factor XIII activity, amount of
      the subunits A and S of factor XIII with rocket electrophoresis. The results
      showed that the propositus had clinical history of bleeding in umbilical cord and
      its stump after birth. Her parents are not consanguineously related and have no
      history suggestive of hemorrhagic diathesis. The propositus has one brother and
      three sisters. One of her sisters died of bleeding of the umbilical cord after
      birth, another died at age of two, but the reason of her death is unclear and the
      remaining siblings are clinically healthy. The propositus had an abnormal urea
      clot lysis test, but the other family members had normal results. For the
      propositus factor XIII activity was 0%. A subunit 0% and S subunit 8.2%. Factor
      XIII activity of her father, her mother and her sister were 25%, 50%, 25%
      respectively. A subunit 52%, 58%, and 58% respectively and S subunit 66%, 68% and
      66% respectively. The results showed that the propositus has a congenital
      deficiency in coagulation factor XIII, and her parents and sister are in fact
      carriers.

PMID- 9592354
TI  - [Impact of platelet derived growth factor in the glomeruli of active lupus
      nephritis].
AB  - Platelet derived growth factor (PDGF) possesses diverse biological activities and
      plays an important role in the pathogenesis of glomeruli nephritis. In order to
      elucidate the relationship between PDGF and the disease activation in lupus
      nephritis, PDGF was observed in renal biopsy specimen from 9 cases of lupus
      nephritis (7 cases with active and 2 cases with inactive lesions) by
      immunohistochemistry using 4-layer PAP method. The mRNA expression of PDGF-A and 
      B chain, and the receptor of PDGF-B were analyzed by RT-PCR. It was found that
      the levels of mRNA expression of PDGF and its receptor were much higher in
      patients with active lesions in glomeruli as compared with those without active
      lesions, there changes were paralleled with the degree of hematuria in these
      patients. Noted that there was no correlation between the expression of PDGF and
      the cellular proliferation in glomeruli of lupus nephritis. These results
      indicate that PDGF is a critical mediator for inducing active lesion in glomeruli
      of lupus nephritis. The effect of PDGF antagonist in the regulation of glomerular
      damage in lupus nephritis need to further elucidate.

PMID- 9592355
TI  - [The relation between coronary vasospasm and coronary obstructive lesions in
      patients with variant angina].
AB  - A series of 38 patients with variant angina in whom coronary arteriography was
      performed was reviewed to investigate the relation between coronary vasospasm and
      coronary obstructive lesions. 10 of the 38 (26.3%) patients had completely normal
      coronary arteriograms; 4 (10.5%) had insignificant coronary artery disease (< 50%
      stenosis); 24 (63.2%) had significant (> or = 50% stenosis) coronary artery
      disease, including single vessel disease in 12 cases, multiple vessel disease in
      11 cases and left main trunk disease in one case. The results of this study
      showed that the incidence of coronary vasospasm increased with the severity of
      coronary stenosis and was highest at 75%-90% stenosis of the ischemia-related
      artery in those patients with significant coronary disease. In this study of 38
      patients, coronary vasospasm involved the left anterior descending artery (LAD)
      in 25 patients (65.8%), right coronary artery (RCA) in 10 (26.3%) and left
      circumflex artery (LCX) in 2 (5.3%), but in patients with in significant stenosis
      (< 50%), LAD was involved in 50.0%, RCA in 42.9% and LCX in 7.1%. These results
      indicate that coronary vasospasm occurs frequently in patients with severe
      stenosis of the LAD.

PMID- 9592356
TI  - [Helicobacter pylori infection and gastric mucosa-associated lymphoid tissue
      hyperplasia].
AB  - The association of Helicobacter pylori (Hp) infection with mucosa-associated
      lymphoid tissue (MALT) hyperplasia in gastric mucosa was investigated. The
      results showed that the incidence of Hp infection increased as the degree of the
      mucosal injury was aggravated, but the prevalence of lymphoid follicles in the
      mucosa with atrophic antritis was much more than in the mucosa without the
      atrophic and the frequency of detecting Hp and intestinal metaplasia in the
      mucosa with lymphoid follicles significantly increased, as compared with the
      mucosa without it. These findings suggest that gastric MALT hyperplasia induced
      by Hp infection may lead to destruction of gastric glands through
      hypersensitivity.

PMID- 9592357
TI  - [Predictable value of fasting blood glucose level for the incidence of non
      insulin-dependent diabetes mellitus].
AB  - In order to investigate the predictable value of fasting blood glucose (FBG)
      level for the incidence of non-insulin-dependent diabetes mellitus (NIDDM), 638
      nondiabetic subjects who were investigated in 1986 (including 341 subjects with
      normal glucose tolerance and 297 subjects with impaired glucose tolerance) were
      reexamined in 1992. The results showed that the 6-year-incidence of NIDDM was
      significantly increased with rising of baseline FBG level. After adjusting for
      age, sex and body mass index (BMI), proportional hazard regression analysis
      showed that FBG level in impaired glucose tolerance group was positively
      associated with the development of NIDDM (P = 0.0001). Subjects with mean FBG
      level of 5.19 mmol/L had a higher risk of developing NIDDM than subjects with
      mean FBG level of 4.61 mmol/L (RR 2.1, 95% CI 1.19-3.74, P = 0.01). The risk
      ratio of NIDDM was further increased in the group with mean FBG level of 6.l5
      mmol/L (RR = 2.9, 95% CI 1.79-4.59, P = 0.0001). The result indicates that FBG
      level is an independent risk factor for the development of NIDDM.

PMID- 9592359
TI  - [Advances in the study of thrombopoietin].

PMID- 9592358
TI  - [The clinical significance of changes in lung function, oxygen consumption and
      some bio-active substances in immigrants into high altitude].
AB  - Lung function was assayed in 40 healthy adults who moved to high altitude area
      (Lhasa, 3,658 m above sea level, Group A) recently and 160 who had lived for a
      long period of time (Group B). Oxygen consumption was also measured and serum
      triiodothyronine (T3), thyroxin (T4), reverse triiodothyronine (rT3), endogenous
      digitalis factors (EDF), plasma renin activity (PRA), angiotensin II (AII),
      aldosterone (ALD) and the concentration of atrial natriuretic peptide (ANP) were
      determined with radioimmunoassay in 80 of them. The results showed: (1) In both
      groups, lung volume was increased, flow rate of ventilation markedly quickened
      and diffusion enhanced as compared with the normal value; (2) Thyroid function
      was reduced; (3) ANP and EDF were markedly increased and ALD was reduced. AII was
      markedly increased and PRA was normal in Group A but on the contrary in Group B.
      The possible relation of these changes with the length of time of stay at high
      altitude is discussed.

PMID- 9592360
TI  - [Graft-versus-leukemia effects].

PMID- 9592361
TI  - D. H. Lawrence's views on the development of the infant's interpersonal world.

PMID- 9592362
TI  - Patients' representations of therapist, parents, and self in the early phase of
      psychotherapy.

PMID- 9592363
TI  - The investigation of self-representational fantasies and its impact on the
      psychoanalytic process.

PMID- 9592364
TI  - The widening of the concept of dissociation.

PMID- 9592365
TI  - Teaching countertransference to residents: a survey.

PMID- 9592367
TI  - Dreams: the convergence of neurobiologic and psychoanalytic perspectives.
AB  - Fromm's Aristotelian statement that "Dreaming is a meaningful expression of any
      kind of mental activity under the condition of sleep" (Fromm, 1951, p. 25) is
      similar to a modern neurobiological conclusion about the dreaming process. The
      current data from the neurosciences lead to the definition of dreams as a
      neuropsychological event during sleep whose manifest contents are affect laden,
      visual, auditory, and kinesthetic. Their functions are adaptive and problem
      solving in themselves. They are part of the brain's connectionist information
      processing system which channel, compare, and integrate current affect-laden
      memories with memories of past successful strategies. Thus, the neurobiological
      perspective of dreams provides an underlying neuroanatomical and information
      processing matrix for the dream process that further supports the current
      psychoanalytic view concerning their assimilative and accommodative functions. In
      conclusion, I would like to return to the termination phase of Mr. M's therapy.
      This patient planned to leave therapy approximately 22 months after the
      occurrence of Dream 2, as this dream had predicted. He was to be married and move
      to another city. Although I felt somewhat anxious about his leaving, despite his
      significant progress, we agreed to a termination date. Just prior to the second
      to-last session Mr. M had the following dream: It took place in a large gothic
      building in a zoo. It is dark and depressing and filled with cages of rhesus
      monkeys. I go around with a nurse to inoculate the monkeys. I am scared of the
      virus. My future wife appears. She is immune to the virus. She is brave and she
      rescues me. The patient seemed pleased in relating his dream, and it offered
      resolution and closure for both of us despite a paucity of discussion. Two years
      later I received a letter from him in which he stated that he was well and had no
      additional "monkey dreams."

PMID- 9592366
TI  - The role of group therapy in the care of persons with AIDS.

PMID- 9592368
TI  - Integrating psychoanalysis and psychodynamic psychotherapy into a residency
      training program.

PMID- 9592369
TI  - Work in progress: mental health and creativity.

PMID- 9592370
TI  - [Intercellular matrix of Bacillus subtilis 271: polymeric composition and
      function].
AB  - It was found that the intercellular matrix of Bacillus subtilis 271 mainly
      consists of alpha-1,4-glucan (65% of dry matter), branched at some C-3 residues
      of the polymeric chain, and poly-D-glutamic acid (19% of dry matter). The
      kinematic viscosity of aqueous solutions of the native matrix was four times as
      great as that of deproteinized matrix. Increasing the pH of aqueous solutions of
      the native matrix from 4 to 6 or decreasing their temperature from 38.5 to 11.5
      degrees C caused a three- and sevenfold increase in the viscosity of these
      solutions, respectively. The integrity of the matrix appears to be essential for
      maintaining the homeostasis of Bacillus subtilis populations.

PMID- 9592371
TI  - [Survival of dissociants of a hydrocarbon-oxidizing Pseudomonas aeruginosa strain
      during storage].
AB  - The survival of R-, S-, and M-dissociants of the hydrocarbon-oxidizing strain
      Pseudomonas aeruginosa K-2 was compared after the storage of the cultures by four
      simple methods for 18 months. The best method was storage on slanted synthetic
      medium with hexadecane under mineral oil; under these conditions, the amount of
      viable cells of all dissociants showed the smallest decrease, and the composition
      of the stored populations underwent the least changes. During storage by other
      methods, the highest survival rate was demonstrated by R-cells, and M-cells were
      the most sensitive; this difference resulted in changes in the composition of
      stored populations. In stored populations of S-cells, which are the most active
      hydrocarbon oxidizers, the relative content of poorly active but more stable R
      cells increased, which could result in a decrease in the hydrocarbon-degrading
      ability of the culture.

PMID- 9592372
TI  - NIH peer review: time for some changes.

PMID- 9592373
TI  - Taking stock of scientific fraud.

PMID- 9592374
TI  - Telomerase and cellular lifespan: ending the debate?

PMID- 9592375
TI  - Biotechnology and food security for the 21st century: a real-world perspective.

PMID- 9592376
TI  - Chloroplast-transgenic plants are not a gene flow panacea.

PMID- 9592377
TI  - Chloroplast-transgenic plants are not a gene flow panacea.

PMID- 9592378
TI  - Genetic ID.

PMID- 9592379
TI  - Researchers wary of fear-based ban on lentivirus gene therapy.

PMID- 9592380
TI  - Hoechst production of recombinant human insulin finally begins after 14-year
      battle.

PMID- 9592381
TI  - Directed evolution patent could have major impact.

PMID- 9592382
TI  - Industry critical of EC ethics survey.

PMID- 9592383
TI  - Salmonella and rivals PREEMPTed from chickens.

PMID- 9592384
TI  - Human artificial chromosomes coming into focus.

PMID- 9592385
TI  - Express together and conquer.

PMID- 9592386
TI  - Ferrying proteins to the other side.

PMID- 9592387
TI  - The Cambrian period of nonviral gene delivery.

PMID- 9592388
TI  - Viral vectors show promise in Colorado.

PMID- 9592389
TI  - Alchemy, enzymes, and the blind-watchmaker.

PMID- 9592390
TI  - Construction of YAC-based mammalian artificial chromosomes.
AB  - To construct a mammalian artificial chromosome (MAC), telomere repeats and
      selectable markers were introduced into a 100 kb yeast artificial chromosome
      (YAC) containing human centromeric DNA. This YAC, which has a regular repeat
      structure of alpha-satellite DNA and centromere protein B (CENP-B) boxes,
      efficiently formed MACs that segregated accurately and bound CENP-B, CENP-C, and
      CENP-E. The MACs appear to be about 1-5 Mb in size and contain YAC multimers.
      Structural analyses suggest that the MACs have not acquired host sequences and
      were formed by a de novo mechanism. The accurate segregation of the MACs suggests
      they have potential as vectors for introducing genes into mammals.

PMID- 9592391
TI  - Intercellular delivery of functional p53 by the herpesvirus protein VP22.
AB  - The herpes simplex virus type 1 (HSV-1) virion protein VP22 exhibits the
      remarkable property of intercellular trafficking whereby the protein spreads from
      the cell in which it is synthesized to many surrounding cells. In addition to
      having implications for protein trafficking mechanisms, this function of VP22
      might be exploited to overcome a major hurdle in gene therapy, i.e., efficient
      delivery of genes and gene products. We show that chimeric polypeptides,
      consisting of VP22 linked to the entire p53 protein, retain their ability to
      spread between cells and accumulate in recipient cell nuclei. Furthermore the p53
      VP22 chimeric protein efficiently induces apoptosis in p53 negative human
      osteosarcoma cells resulting in a widespread cytotoxic effect. The intercellular
      delivery of functional p53-VP22 fusion protein is likely to prove beneficial in
      therapeutic strategies based on restoration of p53 function. These results,
      demonstrating intracellular transport of large functional proteins, indicate that
      VP22 delivery may have applications in gene therapy.

PMID- 9592392
TI  - An oncolytic viral mutant that delivers the CYP2B1 transgene and augments
      cyclophosphamide chemotherapy.
AB  - Herpes simplex viruses type 1 (HSV-1) with an inactivated viral ribonucleotide
      reductase (Hsrr, ICP6) were designed to target tumor cells with upregulated
      mammalian ribonucleotide reductase (mRR), an enzyme whose expression is regulated
      by the p16/pRB tumor suppressor pathway. A recombinant HSV-1 was generated by
      knock-out of Hsrr and insertion of the rat CYP2B1 transgene responsible for the
      bioactivation of the prodrugs, cyclophosphamide and ifosfamide. The mutant virus
      replicated selectively in rat and human tumor cells that express mRR. Addition of
      cyclophosphamide potentiated oncolytic effects against cultured tumor cells and
      subcutaneous tumor xenografts established in athymic mice.

PMID- 9592393
TI  - Novel anti-brain tumor cytotoxins specific for cancer cells.
AB  - The vast majority of brain cancers (gliomas) express a receptor (R) for
      interleukin 13 (IL13). In order to achieve specific targeting of the IL13R in
      gliomas, we have mutagenized human (h) IL13. The mutation was made to alter IL13
      interaction with the shared functional IL13/4 normal tissue receptor, but not
      with the glioma-associated receptor. We have thus produced hIL13.E13K (glutamic
      acid at position 13 changed to lysine) and fused it to derivatives of Pseudomonas
      exotoxin A. The hIL13.E13K-based cytotoxins are less active on normal cells and
      thus less toxic, and are better antitumor agents compared with the cytotoxins
      containing nonmutagenized hIL13.

PMID- 9592394
TI  - Homologous and heterologous protection after single intranasal administration of
      live attenuated recombinant Bordetella pertussis.
AB  - While single-dose mucosal immunization is best achieved by the use of attenuated
      live microorganisms, attenuation generally results in decreased immunogenicity.
      We attenuated Bordetella pertussis by the deletion of the pertussis toxin gene. A
      single intranasal administration of this strain protected against subsequent
      challenge as well as did the parent strain and better than immunization with
      commercial vaccine. Unexpectedly, this attenuation resulted in increased
      immunogenicity against the protective antigen filamentous hemagglutinin (FHA). In
      addition, immunogenicity was also enhanced against the Schistosoma mansoni
      Sm28GST genetically fused to FHA, resulting in protection against the parasite,
      as characterized by a reduction in worm burden and egg charge, after a single
      intranasal administration. Thus, attenuated recombinant B. pertussis strains are
      promising vectors for the simultaneous protection against pertussis and
      heterologous diseases by a single intranasal administration.

PMID- 9592395
TI  - Enhanced molecular mimicry of CEA using photoaffinity crosslinked C3d peptide.
AB  - Antigen mimicry of using anti-idiotypic antibodies for use as cancer vaccines has
      been disappointing due to the weak immunogenicity of immunoglobulin variable
      domains. To enhance the immunogenicity of an anti-idiotype vaccine we
      incorporated a molecular adjuvant peptide into the antibody. The peptide is
      derived from the C3d region known to bind CR2 receptors on B-cells. A
      photoreactive peptide is synthesized that affinity-labels a single site in the
      antibody variable domain. The molecular adjuvant peptide is crosslinked to the
      anti-idiotype mimetic by chemical means without modifying other sites on the
      antibody. The C3d-conjugated anti-idiotype antibody induces a strong idiotype and
      antigen-specific response in mice.

PMID- 9592396
TI  - Evolving catalytic antibodies in a phage-displayed combinatorial library.
AB  - In vitro affinity maturation for evolving catalytic antibodies has been
      demonstrated by generating a diverse repertoire of the appropriate
      complementarity-determining regions on a phage surface. Phage display is followed
      by a selection based on binding to an altered antigen that was not used at the
      time of immunization, and provides variants with new catalytic activity and
      substrate specificity. This library format reduces the time needed to isolate the
      desired catalytic antibody fragments to under 2 weeks.

PMID- 9592397
TI  - Controlled proliferation by multigene metabolic engineering enhances the
      productivity of Chinese hamster ovary cells.
AB  - The eukaryotic cell cycle is regulated by a complex network of many proteins.
      Effective reprogramming of this complex regulatory apparatus to achieve
      bioprocess goals, such as cessation of proliferation at high cell density to
      allow an extended period of high production, can require coordinated manipulation
      of multiple genes. Previous efforts to establish inducible cell-cycle arrest of
      Chinese hamster ovary (CHO) cells by regulated expression of the cyclin-dependent
      kinase inhibitor (CDI) p21 failed. By tetracycline-regulated coexpression of p21
      and the differentiation factor CCAAT/enhancer-binding protein alpha (which both
      stabilizes and induces p21), we have achieved effective cell-cycle arrest.
      Production of a model heterologous protein (secreted alkaline phosphatase; SEAP)
      has been increased 10-15 times, on a per cell basis, relative to an isogenic
      control cell line. Because activation of apoptosis response is a possible
      complication in a proliferation-arrested culture, the survival gene bcl-xL was
      coexpressed with another CDI, p27, found to enable CHO cell-cycle arrest
      predominantly in G1 phase. CHO cells stably transfected with a tricistronic
      construct containing the genes for these proteins and for SEAP showed 30-fold
      higher SEAP expression than controls.

PMID- 9592398
TI  - Inhibition of a starch-granule-bound protein leads to modified starch and
      repression of cold sweetening.
AB  - We have cloned a gene involved in starch metabolism that was identified by the
      ability of its product to bind to potato starch granules. Reduction in the
      protein level of transgenic potatoes leads to a reduction in the phosphate
      content of the starch. The complementary result is obtained when the protein is
      expressed in Escherichia coli, as this leads to an increased phosphate content of
      the glycogen. It is possible that this protein is responsible for the
      incorporation of phosphate into starch-like glucans, a process that is not
      understood at the biochemical level. The reduced phosphate content in potato
      starch has some secondary effects on its degradability, as the respective plants
      show a starch excess phenotype in leaves and a reduction in cold-sweetening in
      tubers.

PMID- 9592399
TI  - International patent filing. Factors to consider in deciding when and where to
      file outside the United States.

PMID- 9592400
TI  - Laboratory strategies for the year 2000 problem.

PMID- 9592401
TI  - High-throughput screening. Advances in robotics and miniturization continue to
      accelerate drug lead identification.

PMID- 9592402
TI  - AARN practice consultants find RNs still reporting high rate of safety concerns.

PMID- 9592404
TI  - Beyond the call.

PMID- 9592403
TI  - DNR orders and "futility".

PMID- 9592405
TI  - Bullying and workplace abuse.

PMID- 9592406
TI  - Rural support for hepatitis C.

PMID- 9592407
TI  - Interferon education: the need.

PMID- 9592408
TI  - Demystifying acid-base regulation.
AB  - Acid-base imbalances may have serious clinical implications for all patients. The
      maintenance of homeostasis within the body is intimately linked to the balance of
      acids and bases within the body. Any disturbance in this balance will adversely
      effect all cellular metabolism and ultimately the functioning of vital body
      systems. Figure 3 may help you to understand the integration of the mechanisms
      which regulate acid-base balance in the body.

PMID- 9592409
TI  - Cutting corners.

PMID- 9592410
TI  - Clinical nurses wanted.

PMID- 9592411
TI  - The risk takers.

PMID- 9592412
TI  - Caring for the carers during transplant surgery.
AB  - Staff working in theatre departments play a vital role in organ retrieval.
      However, many find involvement with organ donation uncomfortable and sometimes
      distressing. They may also have misunderstandings about what takes place before
      and after the retrieval operation. This article will examine the issue of organ
      donation from the perspective of the operating theatre staff and offer insight
      into the process of organ donation prior to and following the retrieval surgery.

PMID- 9592413
TI  - Body image: a patient's perspective.

PMID- 9592414
TI  - Nursing the adult experiencing pain.

PMID- 9592415
TI  - Educational preparation of nurses to meet the needs of human immunodeficiency
      virus (HIV) infected patients.

PMID- 9592416
TI  - Alison Bell Memorial Writer's Award. Something in the air.

PMID- 9592417
TI  - Alison Bell Memorial Writer's Award. Clinical audit: the key to effective nursing
      practice.

PMID- 9592418
TI  - A nurse's scope of practice, control, and diathermy in theatres.

PMID- 9592420
TI  - The Chris Gill column. Three point eight.

PMID- 9592419
TI  - Alison Bell Memorial Writer's Award. The nurse as first assistant to the surgeon:
      implications of expanding practice within the operating department.

PMID- 9592421
TI  - Home healthcare nursing in the managed care environment. Part I. Managed care:
      and overview.
AB  - Dramatic changes in the provision of healthcare from fee-for-service to managed
      care have had a definitive impact on consumers as well as providers. As providers
      and recipients of healthcare, home care nurses must be knowledgeable about
      managed care and Health Maintenance Organizations (HMOs): This article, part 1 of
      a two-part series, discusses the tenets of managed care and the different types
      of HMOs. Part 2, in next month's issue, discusses the historic background of home
      care and home care nurses perceptions of the impact that managed care has on
      clients and the practice of home care nursing.

PMID- 9592422
TI  - Caring for a patient's basic needs first.

PMID- 9592423
TI  - Reducing the risk of needlestick injury associated with implanted ports.
AB  - Implanted ports give many of our patients a sense of freedom that they have not
      known since they have been sick. Between infusions, they do not have to be
      reminded constantly of their illness through an external vascular access device.
      However, this patient advantage does carry some degree of risk for the nurse
      working with the patient and the device. Needlestick injuries are serious and
      expensive. There is a financial and emotional toll that cannot be measured. Each
      employer is required by OSHA to have an exposure control plan for eliminating or
      minimizing employee exposure to bloodborne pathogens (OSHA, 1991, 1994).
      Inventions such as the HuberLoc meet the criteria for devices that can reduce the
      risk of injury through engineering controls. Agencies need to know that OSHA
      mandated worker protection can be both easy to use and cost effective. Home care
      nurses need to be more proactive in informing agencies about such devices and
      lobbying for their use.

PMID- 9592424
TI  - ORYX: the next evolution in accreditation.

PMID- 9592425
TI  - Spiritual care and chronically ill clients.
AB  - Today's high-technology, fast-paced healthcare system has left many providers and
      consumers feeling a void in the care provided. Home care nurses play pivotal
      roles in the delivery of spiritual care for chronically ill clients, who are
      usually confined to their homes. This article provides the nurse with
      interventions and techniques to integrate spiritual care into daily practice.

PMID- 9592426
TI  - A day in the life of a home healthcare nurse.

PMID- 9592427
TI  - NOTES: a system for defending patient education through effective documentation.

PMID- 9592428
TI  - Easing end-stage respiratory symptoms in dying patients.

PMID- 9592429
TI  - Parish nursing.

PMID- 9592430
TI  - What are we to do?

PMID- 9592431
TI  - Development and evaluation of computer-based training for pre/post human
      immunodeficiency virus test counseling.
AB  - Computer-based instruction provides flexibility for staff development in the
      context of downsizing and rapid change in hospitals. There is an increasing need
      for nurse involvement in human immunodeficiency virus test counseling in
      hospitals and clinics because the Centers for Disease Control has recommended
      that human immunodeficiency virus testing be offered to all pregnant women. In
      this article, the author describes the development and evaluation of a computer
      based instruction program to train nurses in human immunodeficiency virus test
      counseling.

PMID- 9592432
TI  - Using self-directed learning modules. A literature review.
AB  - The impetus for cost containment may necessitate using teaching strategies
      different from traditional classroom models used in staff development. Educators
      can design self-directed learning modules to educate staff to work more
      effectively with special populations, such as children and elderly patients.
      Encompassing more than 40 years of literature, this review identifies the best
      modular designs, the cost benefits, and various studies about the effectiveness
      of self-directed learning modules.

PMID- 9592433
TI  - An educational approach for patient-focused care. Shifting attitudes and
      practice.
AB  - The authors describe the development, implementation, and evaluation of a
      continuing education course for nurses. Goals of the program were to help change
      attitudes toward care of older persons and to help nurses realign value
      priorities in practice so the concerns, needs, and wishes of patients directed
      care. Learners engaged in dialogues about aging and were introduced to an
      alternative nurse-person process in which the patient was leader. Evaluations
      were positive for nurses and quality of care.

PMID- 9592434
TI  - Writing learning objectives.
AB  - Educators acknowledge the value of objectives in planning educational sessions
      and in evaluating outcomes of those sessions. However, they often express
      frustration in writing educational objectives. The author explores methods of
      writing objectives in the three domains of learning.

PMID- 9592435
TI  - A pharmacology review for private duty nurses using computers and self learning
      concepts.
AB  - Computers, rather than instructors, patiently tutored the nurses, providing them
      with as much practice as necessary to master calculation skills. Instruction was
      consistent and readily available. Traditional printed material also was used
      because of its portability and accessibility. It was reassuring for the nurses to
      have something tangible to review. Program evaluations were positive. Comments
      such as the following were not uncommon: "The computer is a patient tutor; it
      never criticizes or tires"; "It was better than attending a workshop or lecture.
      I really learned the material because I was responsible for my learning."
      Currently, this group of nurses is using computer-assisted instructional programs
      for professional development. With the help and guidance of the PENZANCE staff,
      they overcame their fear of the technology and are now requesting that more
      programs be made available. It was a good experience for all.

PMID- 9592436
TI  - Helping promote infant and toddler development: our role.

PMID- 9592437
TI  - Folic acid for prevention of neural tube defects: pediatric anticipatory
      guidance.
AB  - The incidence of neural tube defects including myelomeningocele, which is one of
      the most common causes of infant and childhood disability, can be substantially
      reduced by folic acid supplementation to the diet of women before and during the
      early stages of pregnancy. All females of childbearing age should be taking folic
      acid supplements of 0.4 mg/day (400 micrograms/day) and consuming a diet rich in
      folate. Because many pregnancies are unplanned, supplementation should not await
      plans for pregnancy. Because pediatric nurse practitioners are in frequent
      contact with both adolescent patients and patients whose mothers are of
      childbearing age, and because pediatric nurse practitioners have an interest in
      preventing neural tube defects in future pediatric patients, they are in a good
      position to provide the necessary anticipatory guidance regarding the critical
      need for adequate folic acid intake by females of childbearing age. This article
      discusses and includes guidelines for providing this anticipatory guidance.

PMID- 9592438
TI  - Migrant farmworker children: health status, barriers to care, and nursing
      innovations in health care delivery.
AB  - Migrant farmworkers are one of the most health care-impoverished populations in
      the United States. Mobility, hazardous occupations, cultural diversity, and low
      socioeconomic status place migrants, and particularly migrant children, at high
      risk for inadequate health care and preventable health problems. This article
      presents a synthesis of the existing research on migrant demographics, major
      health risks, and geographic, financial, and cultural barriers to health care
      access. Innovative nursing strategies to enhance access and improve the health of
      migrant children are explored. These include the use of lay community outreach
      workers, the creation of alternative health care delivery models, and the
      development of information tracking systems.

PMID- 9592439
TI  - The use of nurse practitioners in pediatric institutions.
AB  - INTRODUCTION: Across the United States nurse practitioners (NPs) are used in
      widely different ways even when they are employed in similar settings. The
      purpose of this survey was to describe the use of NPs in pediatric hospitals.
      METHOD: A survey was conducted of the chief nurse officers in pediatric hospitals
      associated with the National Association of Children's Hospitals and Related
      Institutions. Questions were asked about hiring practices, qualifications,
      specialties of the NPs employed, practice arrangements, patient volume, and
      reimbursement. The 22-question survey instrument was developed by the authors.
      The response rate for the survey was 86% (42 of 49 surveys were returned).
      RESULTS: The results identified that most of the hospitals surveyed reported less
      than 50,000 clinic visits per year, NPs were used most often in the specialties
      of neonatology, hematology/oncology, and primary care, more than one half of the
      surveyed hospitals required a masters degree for NPs, only 22% of NPs had
      prescriptive authority, and NPs practiced in 88% of surveyed pediatric hospitals.
      DISCUSSION: Institutional and statutory boundaries continued to limit the
      practice of the NP. Inconsistent education and practice standards and a lack of
      understanding and acceptance of the role also inhibit NPs from being used to the
      fullest potential in pediatric hospitals.

PMID- 9592440
TI  - Anticipatory guidance: having a dog in the family.
AB  - Pediatric nurse practitioners frequently provide families with anticipatory
      guidance. An area often discussed is safety as it relates to growth and
      development. One topic that may not be covered is safety with dogs. Dog bites,
      especially by the family pet, are a common occurrence among children. This
      article assists the nurse practitioner to learn about the unique characteristics
      of the canine, what to teach families and children about safety around dogs,
      responsible dog ownership, and dog training.

PMID- 9592441
TI  - Diagnostic dilemmas in pediatric/adolescent dermatology: scaly scalp.
AB  - Scaly scalp is a common problem in the pediatric and adolescent population. The
      possible causes range from the commonly seen tinea capitis and seborrheic
      dermatitis to rare systemic diseases such as dermatomyositis and Letterer-Siwe
      disease. In all cases a thorough history and physical examination are important
      first steps to successful diagnosis and treatment.

PMID- 9592442
TI  - Respiratory syncytial virus-immunoglobulin intravenous (RSV-IGIV) for respiratory
      syncytial viral infections: Part II.

PMID- 9592443
TI  - Benign congenital jaundice (hyperbilirubinemia): a case of Gilbert syndrome.

PMID- 9592444
TI  - APNs saddled with complex nurse licensure compact.

PMID- 9592445
TI  - Bringing a nutrition curriculum to the schools.

PMID- 9592446
TI  - Assessing competencies for medical procedures as an advanced practice nurse.

PMID- 9592448
TI  - The effect of music in the postanesthesia care unit on pain levels in women who
      have had abdominal hysterectomies.
AB  - Management of pain in the immediate postoperative period is a major concern of
      postanesthesia nurses. Music is a nursing intervention with the potential to
      decrease patient perception of pain in the PACU. The purpose of this study was to
      examine the effect of the use of music on the level of patient pain in the
      immediate postoperative period. A quasi-experimental study design was used with
      three study groups. All patients scheduled for elective abdominal hysterectomies
      using a general anesthesia technique were eligible for participation in the
      study. The setting is a PACU in a community hospital in a suburban area. Subjects
      were asked to rate their pain level every 15 minutes while in the PACU using two
      valid and reliable measures, a verbal pain rating scale and a graphic numeric
      pain intensity scale. Repeated measures of analysis of variance showed no
      differences in level of pain between groups or over time.

PMID- 9592449
TI  - Intricate journey: the path of a manuscript from submission to publication.
AB  - This article traces the path of a manuscript that is submitted for publication
      consideration from the time of its receipt to its ultimate appearance in print.
      The peer review process is explained in detail. Though the process is similar for
      most journals, this article describes the process specific to the Journal of
      PeriAnesthesia Nursing.

PMID- 9592450
TI  - Computer and information technology: software.
AB  - You have that new computer and you are ready to start computing, right? Not
      quite. There is another essential to get started--software. This article focuses
      on software necessary and nice for your computer, and resources that can help you
      in your quest for creating the best possible and easiest to use computer system.
      Once you have gotten everything installed and functioning, you will be ready to
      take the next step--going online. In the next issue of the Journal we will get
      you online and traveling on the information superhighway. Happy computing!

PMID- 9592451
TI  - Critiquing a research article.
AB  - It is often the assignment of the perianesthesia nurse to critique a research
      article to evaluate a suggested procedure or instrument for implementation the
      patient care area. Although details of what should appear in each section of the
      research article have appeared in past reports in this series, this article will
      present an outline for critiquing the entire research manuscript.

PMID- 9592452
TI  - A review of preemptive analgesia.
AB  - Postoperative pain, although frequently encountered, is often undertreated. A new
      method of treating postoperative pain is preemptive analgesia, which seeks to
      prevent or diminish pain before it is caused. A variety of drugs may be used and
      include nonsteriodal anti-inflammatory drugs, local anesthetics, opioids, and
      ketamine. They may be given before, during, and after surgery through the oral,
      intramuscular, intravenous, epidural, intrathecal, and intra-articular routes.

PMID- 9592453
TI  - The problem with problem solving.
AB  - Although managers will always be responsible for solving problems on a daily
      basis, expert problem solving will not ensure survival for an organization. It
      will be more effective in the long run to find out what structural issues support
      the problems and work toward restructuring. This will be the way to move a unit
      or an organization in a direction that can and will be successful in creating a
      future that is resilient to constant change.

PMID- 9592454
TI  - Practical points in the use of albumin for hypovolemia.
AB  - When administering albumin, the nurse must be aware of its mechanism of action
      and understand the desired effects of albumin as therapy. Through this knowledge,
      the nurse will be able to better help the patient in hypovolemic shock.

PMID- 9592455
TI  - Notes from the American Society of Anesthesiologists annual meeting.

PMID- 9592456
TI  - Continuing education: burden or opportunity?

PMID- 9592457
TI  - Thyroid dysfunction in pregnancy.
AB  - Thyroid dysfunction is the second most common endocrine disorder among women of
      childbearing age. When thyroid dysfunction is well controlled, pregnancy outcomes
      are similar to those of women without thyroid disease. Perinatal nurses can
      support the woman affected by a thyroid dysfunction by being knowledgeable about
      the disorder and by providing support and education. The article provides an
      introduction to the physiology and pathophysiology of the thyroid, the effect of
      common thyroid disorders on pregnancy, and clinical management implications for
      perinatal nurses.

PMID- 9592458
TI  - Management of the woman with gestational diabetes mellitus.
AB  - The management of gestational diabetes mellitus focuses on the woman's physical,
      psychosocial, and educational needs. Education is the basis for ensuring the best
      possible outcome for the mother and infant, and the nurse is an integral part of
      the educational process. The woman must acquire new knowledge and skills
      regarding diet, blood glucose monitoring, insulin therapy, and exercise. An
      individualized approach to treatment includes sensitivity to the woman's cultural
      background and learning ability. Compliance with the treatment plan can be
      enhanced by rapport between the woman and health care providers.

PMID- 9592459
TI  - Liver transplant and pregnancy.
AB  - Advances in transplantation medicine present the perinatal health care provider
      with a unique challenge: care of the woman during pregnancy after organ
      transplantation. Pregnancy in liver transplant recipients is complicated by
      hypertension, preeclampsia, anemia, and preterm birth. Neonates born to women
      after liver transplant are not at increased risk for congenital anomalies.
      Evidence to date supports that pregnancy does not have a deleterious effect on
      hepatic graft function or survival if the woman has stable hepatic function
      before pregnancy. The article focuses on the issues involved with perinatal
      management of the woman who is a liver transplant recipient.

PMID- 9592460
TI  - Acute fatty liver of pregnancy.
AB  - Acute fatty liver is a rare but potentially fatal complication of the third
      trimester of pregnancy. Significant improvements in morbidity and mortality have
      been reported in the last several years. Despite accumulation of more data about
      the disease, the exact pathogenesis is unknown. Many women are initially
      misdiagnosed with other more common causes of liver dysfunction during pregnancy.
      It is possible that acute fatty liver is an atypical form of preeclampsia because
      30% to 40% of women with acute fatty liver also have preeclampsia. Supportive
      care and expeditious delivery represent the only known treatment. More data are
      needed about acute fatty liver of pregnancy, but the rare nature of the disease
      and the likelihood that most cases are not reported in the literature limit the
      ability systematically to study causation, disease process, and treatment
      options. Because of the serious condition of most women who develop acute fatty
      liver of pregnancy, collaboration between critical care and perinatal care
      providers is essential for optimal maternal-fetal outcomes.

PMID- 9592461
TI  - Neonatal stress reactivity and cortisol.
AB  - Existing data point to the fact that adrenocortical responses are, at least in
      part, valid representatives of the stress response in term and some preterm
      infants. At the same time, however, there is conflict regarding the use of
      cortisol levels as a diagnostic tool in the neonatal intensive care unit. The
      article reviews the concept of neonatal intensive care unit stress and neonatal
      stress response development and provides a comprehensive literature review of
      cortisol production in term and preterm neonates. A neonatal stress response
      model is presented along with implications for caregiving.

PMID- 9592462
TI  - Transient neonatal diabetes mellitus or an exaggerated steroid response? A case
      study.
AB  - Hyperglycemia is a common finding in the extremely premature neonate, especially
      during the first several days of life. Premature neonates have difficulty
      maintaining normal blood glucose levels in spite of normal or below-normal
      glucose infusion rates. Some infants experience intermittent episodes of
      hyperglycemia throughout the course of hospitalization that typically can be
      related to infection, medications, overinfusion of glucose, or episodes of
      stress. Transient neonatal diabetes mellitus (TNDM) is an uncommon diagnosis that
      is utilized when other reasons for the hyperglycemia cannot be determined. The
      article presents a case study describing an episode of hyperglycemia that could
      have been TNDM or an exaggerated response to the use of dexamethasone.

PMID- 9592463
TI  - Nesidioblastosis: a case study.
AB  - Hypoglycemia is a frequent problem in the neonatal period requiring close
      attention and intervention. Severe, persistent hypoglycemia can have various
      etiologies; one of the most common causes is hyperinsulinism. Nesidioblastosis,
      although rare, is the most common cause of hyperinsulinism in the neonate. If not
      detected early, nesidioblastosis can lead to brain damage and death secondary to
      severe hypoglycemia. The etiology of nesidioblastosis remains unclear. Treatment
      involves maintaining normal blood glucose levels; treatment modalities include
      high glucose infusion rates, use of medications, and surgical intervention. The
      article reviews the pathophysiology and treatment modalities for
      nesidioblastosis. A case study is also presented that describes the clinical
      presentation, treatment, surgical intervention, and postdischarge clinical course
      of an infant with nesidioblastosis.

PMID- 9592464
TI  - Diagnosis and management of congenital hypothyroidism.
AB  - Thyroid hormones are integral to the development and maturation of the central
      nervous system as well as normal growth and development. Comprehensive knowledge
      of the maturation and function of the thyroid gland is essential to understanding
      the pathophysiology of thyroid dysfunction. Early diagnosis and appropriate
      treatment in thyroid disease are imperative for normalization of thyroid hormone
      ratios. Optimal management includes early introduction and strict adherence to a
      regimen of L-thyroxine and routine monitoring of thyroid levels throughout life.
      Parents need to understand the importance of consistent medication administration
      and daily assessment of well-being because these actions are crucial to the
      attainment of an optimal level of development for infants with congenital
      hypothyroidism.

PMID- 9592465
TI  - Reimbursement for WOC (ET) nurse services in an ambulatory setting.

PMID- 9592466
TI  - Continence research in the JWOCN: a report card.

PMID- 9592468
TI  - Measuring the severity of stress urinary incontinence with use of urodynamic
      techniques.

PMID- 9592467
TI  - Anatomy of female continence.
AB  - Various muscle, connective tissue, and neurologic structures within the pelvic
      floor play critical roles in the maintenance of both urinary and fecal
      continence. Recent advances in technology, combined with greater precision during
      anatomic study, have expanded our understanding of the role played by the pelvic
      floor in maintaining continence. The goal of this article is to summarize recent
      research on female pelvic anatomy, with a particular emphasis on the evidence
      base related to urinary incontinence. The content is organized to accomplish
      three aims: (1) identify, within the context of pelvic floor anatomy, the
      structures that comprise the urinary continence system, (2) Describe the
      functional dynamics of urinary continence, including factors in resting urethral
      pressure and pressure transmission, and (3) Present the rationale, technique, and
      interpretation of various methods of measuring pelvic floor function.

PMID- 9592469
TI  - Current status of research on pelvic muscle strengthening techniques.
AB  - In the past 15 years, research on the effect of pelvic muscle exercise on urinary
      stress incontinence has contributed substantially to the understanding of the
      function of the pelvic muscles and the role of pelvic muscle exercise in
      management of stress urinary incontinence. This literature review addresses
      pelvic muscle function, pelvic muscle exercise, pelvic muscle exercise training
      protocols and training aids, changes that result from pelvic muscle exercise, and
      long-term outcomes of pelvic muscle exercise. Emphasis is placed on results or
      research that may be used by the clinician with women who experience stress
      urinary incontinence.

PMID- 9592470
TI  - A shared community-based practice: an alternative model for WOC nursing practice.
AB  - In the past, as the populations in many communities have grown, WOC nurses have
      been hired for each of the major health care facilities located in that
      community. However health care restructuring has caused many local hospitals to
      reevaluate their use of specialty practice nurses, including ET/WOC specialists.
      In response to this trend, a shared community practice model was established that
      has allowed each agency to make use of ET nursing service on an "as needed"
      basis, while maintaining daily accessibility to this important resource person.
      This article describes the evolution and growth of this practice model during the
      past two decades of intense reform in health care delivery.

PMID- 9592471
TI  - Use of a total quality management model to reduce pressure ulcer prevalence in
      the acute care setting.
AB  - As the population ages and becomes more frail, pressure ulcer prevalence and
      incidence within specific care settings are being evaluated through outcomes
      review. This article summarizes the process and outcomes of an ongoing prevalence
      study at a 300-bed acute care community hospital. All patients on the adult
      medical, surgical, and critical care units were examined regularly by the "Rear
      Admirals," a team comprising a skin care resource person and a nursing unit
      representative. The Total Quality Management model, characterized by the phrase
      "Plan-Do-Check-Act," was used to address barriers to quality care. Findings
      during that time prompted changes in policies, products, protocols, work
      assignments, and documentation tools. The outcomes achieved demonstrated the
      effectiveness of those strategies. After implementation of the Total Quality
      Management model at our Institution, the prevalence of patients with nosocomial
      pressure ulcers was reduced by 83%.

PMID- 9592472
TI  - Latex allergy and the WOC nurse: a review of the literature.
AB  - The WOC nurse is familiar with products used to manage skin care. Latex
      sensitivity and allergy is becoming epidemic in the United States and is being
      studied by the Centers for Disease Control and Prevention (CDC) because of its
      life-threatening consequences. Education and prevention from further exposure
      must be addressed by health care workers. With the wealth of information on
      manufactures and their products, and a basic understanding of cellular
      immunology, the WOC nurse can facilitate the move toward either a latex-free or
      latex-safe environment for patients and health care staff.

PMID- 9592473
TI  - Abdominal wound with enterocutaneous fistula: a case study.
AB  - The care of an elderly male surgical patient with an enterocutaneous fistula
      located in an abdominal wound is described. The fistula is believed to have been
      related to multiple surgeries, wound dehiscence, and malnutrition. This article
      presents a brief overview of enterocutaneous fistulas and a pictorial
      demonstration of an alternative wound management technique that was used
      intermittently over several months to contain corrosive intestinal effluent until
      a commercial wound manager could be instituted.

PMID- 9592474
TI  - Providing a self-catheterization prosthesis for a handicapped client.

PMID- 9592475
TI  - [Nutrition factors and breast cancer. Phyto-estrogens and trans-fatty acids as
      potentially protective substances].

PMID- 9592476
TI  - [Antibiotic therapy of septicemia--escalation or reduction?].

PMID- 9592477
TI  - [Pleasure or frustration? Satisfaction of nursing students with the choice of
      their profession at the end of their second school year].

PMID- 9592479
TI  - [Effective therapy versus health care costs. With united force: wound healing
      needs team work].

PMID- 9592478
TI  - [Care of wounds today].

PMID- 9592480
TI  - [Wound treatment by vacuum sealing].

PMID- 9592481
TI  - [A humid environment will propagate physiological wound healing].

PMID- 9592483
TI  - [Why patients rarely ring their bell].

PMID- 9592484
TI  - [Noise and hectic].

PMID- 9592485
TI  - [Protocol of a nocturnal explantation].

PMID- 9592486
TI  - [Balint groups: helpful methods in difficult situations. Bold thinking--careful
      acting].

PMID- 9592487
TI  - [Current Swiss nursing research. Impressions].

PMID- 9592489
TI  - [When the law does not bring justice].

PMID- 9592488
TI  - [Facing a crisis. How to care for a patient with a stoma].

PMID- 9592490
TI  - [The systemic approach (1). Understanding the world in its complexity].

PMID- 9592491
TI  - [Caring for the alcoholic patient and his family at the end of his life. What is
      needed is openness, tolerance and tact...].

PMID- 9592492
TI  - [The avant-garde of nursing research].

PMID- 9592493
TI  - [Kinesthesis for the dying. Moving and touching to the end].

PMID- 9592494
TI  - [Floral art, nature and well-being. The resources of the plant world].

PMID- 9592495
TI  - [Management of pain by the nursing staff. The patient is in pain: what does the
      nurse do?].

PMID- 9592496
TI  - Neonatal cardiovascular pharmacology.
AB  - Neonates present with a variety of cardiovascular problems that require
      pharmacologic intervention. Pharmacologic manipulation of the ductus arteriosus
      and pharmacologic augmentation of cardiac output are the focus of this article.
      Guidelines for nursing assessment and clinical monitoring of neonates receiving
      cardiovascular drugs are included.

PMID- 9592497
TI  - Ontogeny of the gastrointestinal system and its impact on feeding the preterm
      infant.
AB  - The nutritional management of premature infants is a challenging area for
      neonatal clinicians for a number of reasons. These include lack of knowledge
      about when, what, and how to feed; limited clinical experience; and wide
      variations in practice. New practices in the nutritional management of premature
      infants must take into consideration the structural and functional maturity of
      the gastrointestinal system and environmental influences on this system. This
      article presents current knowledge of embryology and ontogeny of the premature
      infant's gastrointestinal system and explains how this knowledge may be applied
      to clinical practice.

PMID- 9592498
TI  - Developmentally supportive care in a neonatal intensive care unit: a research
      utilization project.
AB  - PURPOSE: To implement three aspects of developmental care: lower noise levels,
      decreased light levels, and flexed, midline positioning. DESIGN: Research
      utilization project. The developmental care interventions were implemented on a
      daily basis for two hours of "quiet time" during each eight-hour shift. SAMPLE:
      49 infants with mean gestational ages of 35.1 +/- 3.2 weeks and mean weights of
      2,107 +/- 464 gm. MAIN OUTCOME VARIABLE: Noise levels, light levels, and flexed
      midline positioning. RESULTS: Mean light levels and mean noise levels decreased
      during "quiet time" on all three shifts during the project. Optimal positioning
      was achieved 78 percent of the time during the project period observations.

PMID- 9592499
TI  - A neonatal care map based on gestational age.
AB  - Care maps have been used successfully in the adult population. To evaluate the
      use of these patient care models in the neonatal population, one Level III NICU
      compared data on 146 infants who ranged in gestational age from 24 to 33 weeks.
      Nine clinical benchmarks were identified as serving to define the infant's
      progress. These nine benchmarks were back to birth weight, extubation,
      discontinuation of hyperalimentation, discontinuation of NCPAP, feeding trial via
      orogastric tube, weaned to open crib, discontinuation of oxygen, full oral
      feedings, and discharge home. Gestational age was consistently observed to be the
      dominant determinant of the infant's readiness to achieve these physiologic
      tasks. The result of this project is a neonatal care map, based on gestational
      age. This care map outlines the expected treatment and response of the neonatal
      patient. It serves as a guide for both clinicians and families.

PMID- 9592500
TI  - A coach named Sue.

PMID- 9592501
TI  - Smart ways to work.

PMID- 9592502
TI  - Hemophilia in the newborn: a case presentation.

PMID- 9592503
TI  - Whatever happened to Baby Doe?

PMID- 9592504
TI  - The visitation policy.

PMID- 9592505
TI  - A closer look at neonatal sucking.

PMID- 9592506
TI  - The Quality Assurance Agency for higher education (England) nursing subject
      review.

PMID- 9592507
TI  - New skills required of nurse tutors in the UK: a study within two Project 2000
      pilot schemes for pre-registration nursing courses.
AB  - This paper examines the development of new skills required of nurse tutors as
      nursing schools integrate with institutions of higher education. The findings
      from part of a larger study, describing significant changes in the role of nurse
      tutors in the UK, in two demonstration Project 2000 districts. A case study
      approach was adapted for the study. Qualitative and quantitative data were
      collected over a 15-month period from a diversity of perspectives. The focus was
      on nurse teachers themselves. The results indicated that as nursing entered into
      the arena of higher education, a majority of nurse tutors would need to develop
      and deploy effective skills in facilitating learning, clinical supervision and
      communication. The findings also showed that a significant number of nurse tutors
      would need to acquire new skills in curriculum innovation, continuous assessment
      of theory and practice, marketing, negotiation, entrepreneurial work, research
      and clinical audits.

PMID- 9592508
TI  - Social and demographic characteristics of young and mature aged nursing students
      in Australian universities.
AB  - This national study compares the social and demographic characteristics of direct
      and delay entry students in a control group of 1551 students in higher education
      programmes in 1987 and 1990 with the national study group of 2295 students
      sampled in 1995. Using a specially constructed socioeconomic variable for
      comparison the analyses demonstrated a significant difference in the
      socioeconomic level of the household for the younger aged group but not for the
      mature aged group. There was also a significant difference between males and
      females in their age of entry patterns. Furthermore, there was a significant
      difference in the location of school attended for most of their secondary
      education for the younger aged group but not for the mature aged group. For both
      groups there was a significant difference in the number of siblings, the level of
      education attained by the mother and the income received by the mother in the
      households of the control and study groups. Logit analysis revealed that there
      was a significant interaction between the household variables: socioeconomic
      status, number of siblings, and income received by the mother of the respondents
      in the control and study groups for the younger age group but not for the mature
      age group. This interaction for the younger age group, plus the finding that
      nursing students were more likely to delay their Higher Education Contribution
      Scheme (HECS) payment than other university students suggests that politicians
      need to take great care in any changes to current HECS payments as such changes
      could upset the delicate social balance that has been achieved in nursing
      recruitment in Australia.

PMID- 9592509
TI  - Understanding nursing students' stress: a proposed framework.
AB  - A paucity of comprehensive research, as well as inconsistent application of
      theories/conceptual frameworks, have resulted in a limited knowledge of stress in
      nursing students. The purpose of this paper is to establish a framework for
      understanding the stress/coping/adaptation process in the nursing student
      population. To this end, Pollock's Adaptation Nursing Model (Pollock 1984) is
      discussed and subsequently recommended as a possible alternative. Utilization of
      this framework as an organizing construct for the paper facilitates a
      comprehensive review of recent literature related to stress in undergraduate
      nursing students. In addition, it is proposed that Pollock's model can provide
      nurse educators, practitioners, administrators and researchers with a framework
      for understanding nursing students' stress.

PMID- 9592511
TI  - Nurses' understanding of physical science in nursing practice.
AB  - When science educators teach nurses, their primary aim should be to help them to
      develop understanding of their world of nursing. From a study of registered
      nurses' conceptions of the physical science underlying their clinical practice,
      we assert that nurses' understanding of the physical sciences is inadequate in
      terms of the competencies required of them as nurses. Rather than respond to this
      contention by altering the content of physical science units in nursing courses,
      we propose that those who teach nurse students should look more carefully at
      factors that influence nurses' learning: these factors are images of nursing,
      shared experience and shared language. We maintain that these factors should not
      be ignored but can be used to advantage in teaching science to nurses.

PMID- 9592510
TI  - The effectiveness of tutorials in behavioural sciences for nurses: an action
      learning project.
AB  - As the first round of an action research project, this paper describes a between
      methods triangulation process which examines the effectiveness of tutorials in a
      post-registration nursing degree course. The major concerns of the research team
      were with student learning approaches and student satisfaction. The research
      utilized a pre-/post-test experimental design as well as descriptive designs
      including non-participant observation of tutorials, tutor journal keeping and
      student interviews, to study the effects of a change from theory-based to
      learning process-based tutorials. The experimental design utilized the 'study
      process questionnaire' and the 'approaches to study inventory'. Two experimental
      groups showed a significant change in pre-/post-test scores. The qualitative data
      indicated that there were differences in the ways in which these two groups
      operated. The qualitative data also indicated that students were largely
      subscribing to achieving approaches and that satisfaction with tutorials was
      mainly related to relevance to the previous lecture as well as the perceived
      contribution to course assessment. As a consequence of this study it was
      concluded that the efficiency of tutorials could be increased by reducing the
      number of assignments, designing a set of specific tutorial activities that
      integrate theory and process, and having an explicit tutorial group formation
      policy.

PMID- 9592512
TI  - Stating the case for nursing research ethics committees: a discussion paper.
AB  - Progression of nurse education from apprentice to educational courses in response
      to demands for strengthening professional status has led to an increase of
      nursing research proposals at Level 3 and beyond. Accordingly, the demands on
      ethics committees in considering ethico-legal aspects of such proposals have also
      risen. Historically, this function has fallen to (medical) local research ethics
      committees. This paper considers one centre's response in creating a nurse-led
      research ethics committee to function in a symbiotic partnership with its medical
      counterparts. The authors consider arguments for and against such a committee,
      suggesting that nurse-led groups are generally more tolerant of the diversity
      revealed within nursing research proposals, including both quantitative and
      qualitative studies, than medical committees who are arguably steeped in the
      empirical tradition. The authors also consider the future viability of small
      ethics committees against the backdrop of national reorganization of nurse
      education. They contend that whilst organizational factors may encourage creation
      of regionally based multidisciplinary committees, the value of discrete local
      nurse-led ethics groups cannot be underestimated, and such groups should be
      retained.

PMID- 9592513
TI  - Process recording: of what value is examining nursing interaction through
      assignment work?
AB  - This paper comprises a brief examination of the concept of process recording and
      its current applications in nursing and health-related professions. The possible
      benefits and problems of using the process recording tool as a summative
      assignment method within a nursing diploma course will be discussed in the light
      of experience at one former college of health in the North of England. The author
      argues that the process recording assignment offers a useful means of relating
      communication theory to practice and an opportunity for students to engage in
      reflection on their practice in a structured way.

PMID- 9592514
TI  - Specialist education and practice in nursing: an Australian perspective.
AB  - In this paper, we argue that specialist nurses occupy a strategic position in the
      Australian health care system and will continue to do so in the future. From a
      careful consideration of the literature describing past, present and future
      nursing practice and education, we conclude that specialist nurses with
      appropriate skills gained through lifelong learning and experience are the nurses
      to lead and foster the future practice of nursing. The role of current nurse
      educators is to provide time-sensitive education programmes that will facilitate
      the development of such skills.

PMID- 9592515
TI  - Using clinical databases in tertiary nurse education: an innovative application
      of computer technology.
AB  - This paper provides an initial report of an educational innovation in nursing
      that promotes exchange of information and close cooperation between hospitals and
      a university. Data from a computerized nursing care planning system are used as
      the basis for the design of the acute care clinical component of the nursing
      curriculum. The project has been developed with the aim of minimizing the theory
      practice gap and making the transition from university to hospital an easier
      process for students and new graduates. From the very early stages of the
      project, it was recognized that the introduction of new computer-based
      innovations or educational technology, in itself, would not necessarily improve
      teaching and learning. Therefore, strong emphasis was placed on how the database
      would be used as the basis for sound curriculum development while maintaining the
      clinical and practical focus required by students. Difficulties associated with
      the project, ranging from lengthy legal negotiations to the challenge of
      integrating a curriculum strongly based on critical reflection and problem
      solving with a highly prescriptive hospital database are reported. The project
      not only provides an example of the efficient exchange and use of hospital-based
      data for teaching purposes but also provides the groundwork for many potential
      and exciting developments in national and international nursing data exchange.

PMID- 9592516
TI  - Facilitating reflection: from a sage on stage to a guide on the side.
AB  - Reflection as a teaching and learning method has been well-established in nursing
      education. In this study, the aim is to discover the educational concepts which
      could be used by teachers of nursing in order to facilitate reflection.
      Participant observation and interviews were used to collect data. The study
      concludes that (1) purposefulness, (2) activity, (3) collaboration, (4) critical
      thinking and (5) confrontation and support are all key concepts which should be
      used by teachers in the operationalization of reflection. These concepts can also
      be easily remembered as a mnemonic--'PACTS'. Facilitation is about forming a
      PACTS with students enabling them to assume responsibilities for their learning,
      taking centre stage and the teacher moving aside to function as a guide. The role
      of the teacher in facilitation is thus moving a sage on stage to a guide on the
      side.

PMID- 9592517
TI  - Nurse education and professional work: transition problems?
AB  - The purpose of this study was to investigate the transition from a 3-year nursing
      programme to a professional role as a nurse. Eight subjects kept diaries during 2
      months. Data were recorded in a notebook and categorization of data was based on
      interpretation by two independent persons. Results are presented in relation to
      the different categories which became evident from the diaries. A common problem
      for newly registered nurses was the management of paperwork. The more
      administrative work the nurses had, the less time they were able to spend on
      patient-oriented activities. Generally, the nurses felt uncertain about care of
      patients with serious illnesses. All the nurses experienced a high workload and
      also reported difficulties in feeling relaxed during their off-duty time.
      Additional difficulties encountered included knowing the kind of tasks they were
      able to delegate to assistant nurses, and deciding on when it would be
      appropriate to call for a physician. Further research is needed to provide a
      better understanding of the relevance of nurse education for the management of
      the work situations encountered by newly registered nurses.

PMID- 9592519
TI  - Linking outcomes to nurses' roles in health care.
AB  - As the health care industry refines quality assurance and quality improvement
      standards, the accountability of individual care providers is intensifying. Care
      providers work within a system of interdependent roles and functions and
      collaborate to attain the common goal of quality care. A conceptual model was
      developed which relates the achievement of specific outcomes to nurses'
      independent, dependent, and interdependent roles and functions. Empirical
      literature was used to identify outcomes associated with nurses' role functions.
      Outcomes associated with nurses' independent role functions included the
      prevention of complications, clinical outcomes, knowledge of diseases and
      treatments, satisfaction, and cost outcomes. Outcomes associated with nurses'
      dependent role included adverse incidents which caused problems or prolonged
      hospital stays. Outcomes associated with nurses' interdependent role included
      interdisciplinary team functioning.

PMID- 9592520
TI  - A model to manage capitated risk.
AB  - The impact of increasing enrollment in Medicare HMOs will require health care
      providers to develop new strategies in care delivery systems. Key strategies in
      managing risk include health risk appraisals, proactive case management, disease
      management, provider education, and the use of inpatient physician managers.
      Implementing an integrated care management system requires a team approach. The
      physician inpatient manager, nurse case manager, geriatric clinical nurse
      specialist, and social worker composed the health care team charged with
      implementing a care management system responsive to enrollees' needs. A quality
      management plan is essential for tracking patient outcomes and quality indicators
      across the continuum. The focus of promoting wellness and preventing illness
      represents a paradigm shift from the traditional model of episodic care that can
      yield positive financial results.

PMID- 9592521
TI  - Demonstrating APN value in a capitated market.
AB  - To be acknowledged as powerful resources in health care reform, APNs must
      demonstrate their capability to discern and implement cost-effective care. APNs
      are typically associated with services that do not generate revenue. Therefore,
      they need to document their value in terms of improved outcomes, reduced costs,
      improved patient satisfaction, enhanced institutional image, and better health
      care team efficiency. The savings generated by APN consultation and followup for
      patients referred for home TPN was examined in Rochester, NY, using a simplified
      cost analysis and forms. Collection of data does not need to be elaborate. Costs
      can be bundled and examined within the period, simple data collection methods can
      be constructed for details of consultations, and community surveys can provide
      market prices. It is suggested that the analysis follow basic steps: list items,
      examine costs, collect or estimate costs, list all assumptions, then calculate
      total month and daily costs.

PMID- 9592522
TI  - Redesigning emergency care: financial and cost analysis of services provided.
AB  - Developing an interdiscliplinary team to monitor and implement redesign is
      critical to successful, quality outcomes. Analysis of the current status of the
      organization and national trends is essential prior to redesign. Key assessment
      data gathered were: profiling users, payer distribution, inpatient admissions,
      data on types of chronic conditions, DRGs, readmits, short-stay admissions, non
      admits, and outpatient services and charges. Organizational realignment requires
      time and analysis of financial, clinical, and demographic data. The team-building
      framework used in this emergency room redesign was based on a collaborative
      model. A crucial initial step was to get support from the organization's
      executive level of leadership for the new redesign vision. Another factor
      considered essential for a successful outcome was commitment from each member of
      the interdisciplinary team. Communication between the team and staff was a top
      priority.

PMID- 9592523
TI  - Developing new nurse leaders.
AB  - This innovative program was an easily administered and cost-effective method to
      identify and develop new nurse leaders. Successful features of the program were
      (a) the tenure in the ACNM's traineeship position was limited to 1 year, (b) the
      salary expense was just over $1,000 per ACNM per year, [c] the ACNMs were
      protected from publicity and visibility while they learned, and (d) potential
      nurse leaders were identified. After selling the idea to the hospital and nursing
      management, the only major effort needed to begin the program was the development
      of the ACNM job description and the selection of candidates. The rewards far
      outweighed the initial effort.

PMID- 9592524
TI  - Outpatient visit planning: turning episodic care into comprehensive care.
AB  - Outpatient visit planning is a method of identifying a patient's major health
      needs and developing a plan for care on a per visit basis. It assures attention
      to chronic disease followup, prevention, and educational needs in spite of
      patient compliance. The visit planner, ideally a registered nurse, is the focal
      point for coordinating the services of the entire team of ambulatory health
      professionals. Visit planning is the gateway to true comprehensive care.

PMID- 9592525
TI  - Decision support and data warehousing tools boost competitive advantage.
AB  - The ability to communicate across the care continuum is fast becoming an integral
      component of the successful health enterprise. As integrated delivery systems are
      formed and patient care delivery is restructured, health care professionals must
      be able to distribute, access, and evaluate information across departments and
      care settings. The Aberdeen Group, a computer and communications research and
      consulting organization, believes that "the single biggest challenge for next
      generation health care providers is to improve on how they consolidate and manage
      information across the continuum of care. This involves building a strategic
      warehouse of clinical and financial information that can be shared and leveraged
      by health care professionals, regardless of the location or type of care setting"
      (Aberdeen Group, Inc., 1997). The value and importance of data and systems
      integration are growing. Organizations that create a strategy and implement DSS
      tools to provide decision-makers with the critical information they need to face
      the competition and maintain quality and costs will have the advantage.

PMID- 9592526
TI  - A national strategy to reduce health care errors.

PMID- 9592527
TI  - Leading change is leading creativity.
AB  - Leadership is the leading of creativity which leads to creative change. To
      innovate or die is the question that faces our health care future. It is no
      longer enough for us to operate with just our serial, mathematical thinking. We
      must also be concerned about the spirit and the heart and how we integrate this
      into whole brain thinking. The challenge for us is to constantly transform and
      rewire our brains through the creativity process and to rewire the processes of
      the places where we work. We know that we can cultivate and energize our
      organizations through the interplay of serial, parallel, and quantum thinking
      processes. But we can't wait. Health care and the world of nursing are changing
      rapidly. We need the creative processes to build the change needed for the future
      for the care of our patients.

PMID- 9592528
TI  - Career renewal.

PMID- 9592530
TI  - [Liebe Leserin, lieber Leser]

PMID- 9592529
TI  - Index of professional nursing governance.

PMID- 9592531
TI  - ["... we are guests in our patients' homes"].

PMID- 9592532
TI  - [Quality in home care means both professional competence and human quality.
      Interview by Harald Verworner].

PMID- 9592533
TI  - [From Cinderella to princess? Home care in Austria].

PMID- 9592534
TI  - [Problems of professional work in extramural care].

PMID- 9592535
TI  - [A success story from the extramural field].

PMID- 9592536
TI  - When it comes time to donate blood, don't make excuses!

PMID- 9592537
TI  - Future shock in nursing: are you prepared?

PMID- 9592538
TI  - Ultrasound assisted lipoplasty--Part 1: An overview for nurses.
AB  - The use of ultrasound assisted lipoplasty (UAL) to assist in the removal of
      subcutaneous fat has been practiced in Europe for nearly a decade but has only
      recently been practiced in the United States. This article will discuss the UAL
      procedure, its history, regulatory issues, instrumentation and equipment needed,
      clinical protocol, case reports, complications, and future considerations.

PMID- 9592539
TI  - Ultrasound assisted lipoplasty--Part 2: Clinical management.

PMID- 9592540
TI  - Negative pressure wound therapy.
AB  - Negative Pressure Wound Therapy, also known as Vacuum Assisted Closure (V.A.C.),
      is a new treatment in which controlled negative pressure is used to provide
      evacuation of wound fluid, stimulation of granulation tissue, and a decrease in
      bacterial colonization. A brief discussion of the physiology of wound healing is
      accompanied by an explanation of vacuum assisted wound closure. Indications and
      contraindications for V.A.C. are discussed. The authors present several case
      studies of patients with nonhealing wounds who benefitted from V.A.C.

PMID- 9592541
TI  - Tumescent abdominoplasty: full abdominoplasty under local anesthesia with i.v.
      sedation in an ambulatory surgical facility.
AB  - The tumescent technique makes it possible for the surgeon to perform a full
      abdominoplasty with suction-assisted lipoplasty (SAL) contouring without the
      necessity for general anesthesia. Benefits include minimal blood loss, less
      postoperative pain, and limited postoperative bruising. In mid-1996, the co
      author performed his first full abdominoplasty under local anesthesia with i.v.
      sedation in his office operating facility. Since then this technique has been
      used routinely. Patient satisfaction and rapid return to activities of daily
      living are remarkable.

PMID- 9592542
TI  - Jackson-Pratt drains: patient discharge instructions.

PMID- 9592543
TI  - The softer side of research.

PMID- 9592545
TI  - Whistle-blowing: a moral dilemma.

PMID- 9592546
TI  - [Invasion of the personal space of hospitalized patients: adaptation of an
      instrument of measurement in Brazilian culture].
AB  - The invasion of patient's territorial and personal space and its effects have
      been object of several international studies. In view of its importance and
      searching for an instrument of measure to develop research in this area, the
      present study aimed at adapting the instrument "anxiety due to territory and
      space instrucsion questionnaire" to the brazilian culture. Authors fully
      described the phases of this process and utilized the software SPSS for the
      psychometric analysis.

PMID- 9592547
TI  - [Perception of the organizational climate in the surgical center of a specialized
      hospital].
AB  - The aim of this study is to identify how a new team of the surgical center staff
      in a specialized hospital perceive the organization climate. A qualitative
      approach was utilized. As a theoretical reference to measure the organization
      climate, we have used CHIAVENATO, that defines organization climate as the
      interior of an organization that influences its members behavior. The
      organization climate could be favourable, unfavourable or neutral. The speeches
      showed a favourable organization climate considering the adopted methodology.

PMID- 9592548
TI  - [Utilization of the knowledge of communication by graduate nursing students].
AB  - This descriptive study had as main purpose to identify therapeutic communication
      strategies used by Nursing students from the Nursing School of UFMG and the
      Nursing School of UFJF, during their practice. The method used for data
      collection consisted of observation on the interaction between students and
      inpatients and of interviews with the students. The results showed that although
      90% of the students said they learned about communication, they had difficulties
      to practice in the field what they learned as theoretical knowledge.

PMID- 9592549
TI  - [Consultation in the context of interpersonal communication--the clients
      perception].
AB  - This study describes clients perceptions about the nursing consultation, under
      the interpersonal communication context point of view. Data were collected
      through semi-structured interviews, with a sample of 11 (eleven) clients, who
      attended the Diabetes Control and High Blood Pressure Program of the Medical
      Specialities Center of Campo Grande-MS. Results demonstrated clients positive
      perceptions about nursing consultation and nurses and clients difficulties in
      explaining their feelings clearly.

PMID- 9592550
TI  - [Risk factors in patients with arterial hypertension].
AB  - The aim of this research was to verify the habits related to the risk factors of
      one population with arterial hypertension. Seventy individuals were interviewed.
      Authors found that the majority do not practice any kind of physical exercise,
      they do not have leisure activities and need education programs to acquire these
      habits. There are gaps in information, because they have their own experience as
      a reference, in spite of the orientations they received from several
      professionals.

PMID- 9592551
TI  - [Measurements of the gravity of injuries in patients with head injuries by the
      AIS/90 manual and the CAIS/85 chart].
AB  - This study was developed in order to compare the use of the ABBREVIATED INJURY
      SCALE (AIS) and the CONDENSED ABBREVIATED INJURY SCALE (CAIS) as basis to
      calculate INJURY SEVERITY SCORE (ISS) in head injured patients. The results
      showed that the ISS value was equivalent in the majority of the patients (58.51%)
      codified by both scales. Also no statistic differences between the scales were
      perceived when we compared the severity levels as severe, moderate and minor,
      61.38% of the lesions scored by AIS/90 were scored by CAIS/85, too.

PMID- 9592552
TI  - [Precariousness of records of prenatal care in a basic health unit in the city of
      Ribeirao Preto-SP].
AB  - This survey aimed at characterizing the population of pregnant women utilizing
      prenatal care services of a Basic Health Unit in the city of Ribeirao Preto, Sao
      Paulo, Brazil in July 1995 and analyzing the records of the service given to
      pregnant women who went to this Unit in terms of general and specific anamnesis,
      general and tocogynecological physical examination and the diagnostic procedures
      used in this service. The records showed a lack of information about patients'
      general and specific anamnesis, general and tocogynecological physical
      examination and clinical condition, characterizing a more ritualistic procedure.
      Therefore, records did not meet the objectives proposed by the Program for
      Comprehensive Women Health Care of the Ribeirao Preto City Health Department with
      the Sao Paulo State Health Department and the Health Ministry: to ensure good
      quality in women's care service regarding their clinical, gynecological,
      obstetric and mental needs; to identify, prevent, and control risk factors which
      may affect women's health; to diagnose and treat women's pathologies as soon as
      possible, among others.

PMID- 9592553
TI  - [Experiences in special training programs in the education of undergraduate
      nursing students].
AB  - This study presents the experience of the Special Training Program of the
      University os Sao Paulo at Ribeirao Preto College of Nursing-Brazil, since 1989.
      It is a program, directed to a group of twelve undergraduate students who show
      potential, abilities and interest. It provides under the orientation of a tutor
      professor, the conditions to perform extra-curriculum activities, and develop
      scientific studies. The activities carried out by this group of students are: a
      course of foreign language, weekly meetings with the tutor, scientific
      investigation under the orientation of a teacher and discussion of scientific
      themes. These students act like of multiplication agent, disseminating ideas and
      practices borrowed from other students. The program has an excellent reputation
      in the brazilian academic area, and some of the ex-students are attending
      graduate programs, and according to its participants, it provides a personal and
      professional growth, through promoting activities that lead to the integration of
      the academic formation and the future professional activity.

PMID- 9592554
TI  - [Street cleaners: occupational accidents in the city of Ribeirao Preto, State of
      Sao Paulo, Brazil].
AB  - The work of street sweepers is to sweep waste materials thrown at public streets.
      It is considered insalubrious due to the close contact that exposes workers to
      agents present in the urban waste. As street orderlies perform their duties in an
      open environment, they are submitted to different types of problems. The purpose
      of this study is to investigate the registered occupational accidents occurred
      among street orderlies in the city of Ribeirao Preto, State of Sao Paulo, during
      1993 and 1994. Authors aimed at verifying: the number of works that suffered
      accidents and the notified occupational accidents; data related to the
      identification of those accidents at the employer company and specific data
      regarding the occupational accidents. Therefore, authors analyzed the
      occupational health reports recorded at the National Institute of Social Security
      at the Regional Bureau of Health (RBH) and at the employer company. Results were
      shown to the employers and to the RBH. Authors organized meetings to discuss with
      them the occupational problems they found.

PMID- 9592555
TI  - [Situational leadership: structures of reference for the work of head nurses in a
      hospital context].
AB  - Authors studying the theme of leadership developed models that can be applied in
      the organizational context. In the present study, we selected the model proposed
      by Hersey and Blanchard, named Situational Leadership. Through the technique of
      critical incidents, we identified and analyzed the behaviour of nurses from
      surgical units. Based on the analysis of data, we were able to infer that
      situational leadership can be used as a theoretical structure to base nurses'
      leadership skills, in order to improve the quality of nursing care and the
      development of nursing personnel.

PMID- 9592556
TI  - [Accumulation of data about adolescence by nurses: period from 1983 to 1996].
AB  - In the last ten years adolescence has been object of study of many researchers
      and considered by National and International Organizations as an age band with
      priority to actions of promotion, prevention and protection. Many factors
      contributed to this concern with adolescence, between them, we can emphasize the
      importance of this populational contingent that represents 30% of world
      population, besides the questions of precocious pregnancy, AIDS and drugs. As
      nurse researchers, we are interested in experiencing and characterizing
      quantitatively and qualitatively the scientific production about adolescence in
      nursing, using as source of data collection the national specific nursing
      periodicals. Data obtained in this research show that the adolescence theme is
      not explored by the nursing staff, and the most important aspects are related to
      sexuality.

PMID- 9592558
TI  - [Production of nursing knowledge].

PMID- 9592557
TI  - [Ergonomic working conditions for the nursing team in a cardiology unit].
AB  - Aiming at finding out the ergonomics conditions of the nursing personnel in a
      hospital admission unit, the authors utilized as a methodological presupposition
      the search for a global experienced work situation through the analysis of some
      elements as: the man (nursing worker); the work activity (prescribed duty, real
      activities and work position) and the environment (temperature, noise and
      illumination). The authors selected the Cardiology admission unit for the site of
      their research. The results verified that the nursing workers the mentioned unit
      face problems related to salaries, work installations, relationship, work
      organization, levels of formation and the activities executed. The authors
      suggested some recommendations.

PMID- 9592559
TI  - Cymbimicin A and B, two novel cyclophilin-binding structures isolated from
      actinomycetes.
AB  - Two novel metabolites, cymbimicins A and B, were isolated from the culture broth
      of a strain of Micromonospora sp. by screening for cyclophilin binding
      metabolites from actinomycete strains. Cymbimicin A binds to cyclophilin A with a
      high affinity six fold lower than to that of cyclosporin A. The binding affinity
      of cymbimicin B is about 100 times lower. The taxonomy of the producing strain,
      fermentation, isolation, physical and biological properties and structure
      elucidation are described.

PMID- 9592560
TI  - Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis. I. Taxonomy,
      fermentation, isolation and antimicrobial activities.
AB  - A new structural class of the antibiotic, epoxyquinomicins A, B, C and D were
      isolated from the culture broth of the strain MK299-95F4, which was related to
      Amycolatopsis sulphurea. Antimicrobial activity of epoxyquinomicins A and B were
      weak against Gram-positive bacteria, and epoxyquinomicins C and D showed almost
      no antimicrobial activity and no cytotoxicity. All these antibiotics showed
      improvement of collagen induced arthritis in vivo.

PMID- 9592561
TI  - Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis. II. Effect on
      type II collagen-induced arthritis in mice.
AB  - The anti-arthritic effects of epoxyquinomicins on type II collagen-induced
      arthritis in DBA/1J mice were examined. Prophylactic treatment with
      epoxyquinomicins A, B, C and D (1-4 mg/kg) had potent inhibitory effects on type
      II collagen-induced arthritis. In contrast to nonsteroidal anti-inflammatory
      drugs (NSAIDs), epoxyquinomicin C (1-30 mg/kg) had neither an anti-inflammatory
      effect on carrageenan-induced paw edema in rats nor an analgesic effect on acetic
      acid-induced writhing in mice. These results suggest that the mode of action of
      epoxyquinomicins is different from that of NSAIDs and that epoxyquinomicins may
      become useful drugs for the treatment of rheumatoid arthritis.

PMID- 9592562
TI  - Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis. III. Physico
      chemical properties and structure determination.
AB  - The structures of epoxyquinomicins A (1), B (2), C (3) and D (4) were determined
      by spectroscopic studies. Compound 1 was determined to be (5R,6S)-2-(3-chloro-2
      hydroxybenzoylamino)-5-hydroxymethyl-5,6-epo xy- 2-cyclohexene-1,4-dione.
      Compound 2 was revealed to be the dechlorinated derivative of 1. Compounds 3 and
      4 were determined to be the reduced derivative of 2 and 1, respectively.

PMID- 9592563
TI  - Hydroxyakalone, a novel xanthine oxidase inhibitor produced by a marine
      bacterium, Agrobacterium aurantiacum.
AB  - A new xanthine oxidase inhibitor named hydroxyakalone was isolated from the
      culture broth of a marine bacterium Agrobacterium aurantiacum N-81106. Structure
      of hydroxyakalone was determined to be 4-amino-1H-pyrazolo[3,4-d]pyrimidine-3-one
      6-ol by the spectral studies of hydroxyakalone and its permethyl derivative. The
      concentration to induce 50% inhibition (IC50) was 4.6 microM against xanthine
      oxidase.

PMID- 9592565
TI  - Formamicin, a novel antifungal antibiotic produced by a strain of Saccharothrix
      sp. I. Taxonomy, production, isolation and biological properties.
AB  - Formamicin, an antifungal antibiotic, was isolated from the cultured broth of an
      actinomycete strain. The strain was isolated from a soil collected at Setagaya
      ku, Tokyo, Japan, and identified as Saccharothrix sp. MK27-91F2. Formamicin was
      extracted with acetone from cultured mycelia and purified by silicagel and
      Sephadex LH-20 column chromatographies and CPC (Centrifugal liquid-liquid
      Partition Chromatography). Formamicin showed strong antimicrobial activity
      against phytopathogenic fungi.

PMID- 9592564
TI  - Two new components of the aspochalasins produced by Aspergillus sp.
AB  - Aspergillus sp. FO-4282 was found to produce two new components of the
      aspochalasins. Their structures were determined by spectroscopic analyses.

PMID- 9592566
TI  - Formamicin, a novel antifungal antibiotic produced by a strain of Saccharothrix
      sp. II. Structure elucidation of formamicin.
AB  - A novel antifungal antibiotic, formamicin, was isolated from the culture broth of
      Saccharothrix sp. MK27-91F2. The absolute structure of formamicin was
      determinated by spectroscopic and X-ray crystallographic analysis and degradation
      study.

PMID- 9592567
TI  - In vitro antifungal activity of CAN-296: a naturally occurring complex
      carbohydrate.
AB  - The in vitro activity of a naturally occurring complex carbohydrate, CAN-296, was
      evaluated by testing 132 clinical and ATCC isolates of yeast and Aspergillus
      fumigatus, many of which were azole-resistant. The in vitro susceptibility tests
      were performed by standardized broth micro- and macrodilution methods and results
      were compared with those obtained for amphotericin B, fluconazole, ketoconazole,
      flucytosine and the pneumocandin L-733,560. All tested Candida species showed
      highly uniform susceptibility to CAN-296 at concentrations of 0.078 to 0.312
      microgram/ml; non-albicans Candida were as susceptible to CAN-296 as the Candida
      albicans strains. Multi-azole-resistant Candida species were highly sensitive to
      CAN-296. Minimum inhibitory concentration measurements did not differ from
      minimum lethal concentrations by more than two-fold for all tested Candida
      species. Aspergillus fumigatus, on the other hand, showed only moderate
      susceptibility to CAN-296. The kinetics of the anti-Candida activity of CAN-296
      was investigated by kill-curve experiments using C. albicans and C. glabrata and
      the results were compared with those obtain for amphotericin B. CAN-296 was found
      to be rapidly fungicidal in concentrations ranging from 4-16 fold the mean MIC
      value. The broad spectrum of anti-Candida activity together with the rapid
      fungicidal effect make this complex carbohydrate a promising agent for clinical
      use.

PMID- 9592568
TI  - YM-47515, a novel isonitrile antibiotic from Micromonospora echinospora subsp.
      echinospora.
AB  - During the course of our screening for new antibiotics, Micromonospora
      echinospora subsp. echinospora Y-03559J was found to produce a novel isonitrile
      compound, YM-47515 (1) along with a probable degradation product 2. The structure
      of 1 was assigned by spectroscopic analysis including 2D NMR and IR experiments.
      The relative stereochemistry of 1 was also proposed by comparison of spectral
      data with those of a closely related compound aerocyanidin (3). YM-47515 (1)
      showed promising antimicrobial activity against Gram-positive bacteria including
      methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 9592569
TI  - Korormicin, a novel antibiotic specifically active against marine gram-negative
      bacteria, produced by a marine bacterium.
AB  - A novel antibiotic named korormicin was isolated from the marine bacterium,
      Pseudoalteromonas sp. F-420. This strain was isolated from the surface of a macro
      alga Halimeda sp. collected from Palau (the Republic of Belau). The planar
      structure of korormicin was determined by the result of 2D NMR studies and mass
      spectral data. Korormicin had specific inhibitory activity against marine Gram
      negative bacteria, but was inactive against terrestrial microorganisms.

PMID- 9592571
TI  - Structure of sporostatin (M5032), an inhibitor of cyclic adenosine 3',5'
      monophosphate phosphodiesterase.

PMID- 9592570
TI  - Biosynthetic studies on the alpha-glucosidase inhibitor acarbose in Actinoplanes
      sp.: source of the maltose unit.
AB  - To investigate the source of the maltose unit in acarbose, feeding experiments
      using 3H- or 2H-labeled maltose or maltotriose were carried out with resting
      cells of Actinoplanes sp. SN223/29. It was found by experiments with [6"-3H]- and
      [1-3H]maltotriose that a maltose unit from the nonreducing end of maltotriose is
      incorporated into acarbose more efficiently than from the reducing end. However,
      experiments with [6"-2H]- and [2-2H]maltotriose showed that maltose from either
      the reducing end or from the nonreducing end of maltotriose was incorporated into
      acarbose. The results established that acarbose is formed from maltotriose by two
      routes; (1) Sixty percent of the acarbose are formed by attachment of maltose,
      produced by removing a glucose exclusively from the nonreducing end of
      maltotriose, to the pseudodisaccharide core unit. (2) The other 40% of the
      acarbose are formed by direct attachment of maltotriose to the core unit followed
      by loss of the terminal glucose from the reducing end. Furthermore, it was
      observed that there is no scrambling of label between the two glucose moieties of
      acarbose, that maltotriose is a comparably efficient precursor of acarbose as is
      maltose, and that the core unit is enriched up to 50% from the 2H-glucose
      liberated from the deuterated maltotrioses.

PMID- 9592572
TI  - Malonylniphimycin: macrolide antibiotic from Streptomyces hygroscopicus B-7:
      physico-chemical properties and structure elucidation.

PMID- 9592574
TI  - Sulochrin inhibits eosinophil degranulation.

PMID- 9592573
TI  - Trichostatin A and herboxidiene up-regulate the gene expression of low density
      lipoprotein receptor.

PMID- 9592575
TI  - X-ray crystallographies of leucomycin A5 and rokitamycin monomethylacetal.

PMID- 9592576
TI  - Studies on the biosynthesis of terpenoidal compounds produced by actinomycetes.
      2. Biosynthesis of carquinostatin B via the non-mevalonate pathway in
      Streptomyces exfoliatus.

PMID- 9592577
TI  - [Neuro-interventional treatment of cerebrovascular malformations].
AB  - Cerebral vascular malformations are relatively rare diseases, however, their
      clinical impact is high. The group of vascular malformations include arterio
      venous malformations of the brain and of the dura mater (AVM and DAVM) and
      arterial aneurysms. The danger coming from these malformations lies in the ruture
      with following cerebral stroke. Patients may die directly, or suffer from
      numerous deficits as hemipegia, loss of vision or speech and several severe
      cognitive deficits. Early diagnosis and early treatment is most important to
      avoid such complications and to prevent the patients from permanent
      invalidisation. A therapeutic alternative with increasing impact is given with
      the minimal invasive endovascular procedures. Alone, or in combination used with
      Radiosurgery and Neurosurgery, these techniques enable a most optimal and risk
      reduced therapy for the patients.

PMID- 9592578
TI  - [What is the role of Doppler color sonography associated with echo-signal
      enhancing levovist in complementary breast diagnosis?].
AB  - At the women's hospital of the University of Erlangen we performed a prospective
      clinical study to evaluate the use of color Doppler imaging supported by the new
      echo contrast agent Levovist in comparison to clinical examination, B-mode
      sonography, mammography, and MRI. In 40 patients the sensitivity and specificity
      of each method was estimated in predicting the dignity of palpable or
      mammographically detectable tumors of the breast. Prior to and after
      administration of Levovist we recorded the number of vessels, the PI, RI, SD
      ratio, and maximum flow velocity after correction of the angle. Color Doppler
      imaging of the tumor and the surrounding tissue was documented on video tape for
      five minutes after the administration of Levovist. We measured the time until an
      increase and decrease in color signal was detectable. The following
      sensitivities/specificities were found: clinical examination 57.1% (12/21)/73.7%
      (14/19), B-mode sonography 100% (21/21)/84.2% (16/19), mammography 100%
      (21/21)/89.5% (17/19) and MRI 92.3% (14/15)/78.6% (15/18). Without the contrast
      agent color Doppler imaging could not differentiate between malignant and benign
      lesions. There was no significant difference in the perfusion of benign and
      malignant tumors. However, after the administration of Levovist, there appeared
      to be a significant difference for SD-ratio. With a cut-off-level of 3.5 we found
      a sensitivity/specificity of 85% (17/ 20)/78.6% (11/14) for the Doppler method.
      There was a weak correlation between the time of appearance of the augmented
      Signal in color Doppler and the velocity of enhancement of the contrast agent in
      MRI (n = 24, r = 0.47, p = 0.02). Only with the use of a contrast agent was color
      Doppler ultrasound able to support the other methods in pre-operative
      differentiation of benign and malignant lesions in the breast.

PMID- 9592579
TI  - [Detection of aneurysm in subarachnoid hemorrhage--CT angiography vs. digital
      subtraction angiography].
AB  - PURPOSE: The value of CT-angiography (CT-A) for the visualization of intracranial
      aneurysms was more closely defined by comparison with digital subtraction
      angiography (DSA). METHODS: Over a period of 18 months a total of 106 patients in
      whom a subarachnoidal hemorrhage had been detected on native CT were examined in
      parallel by spiral CT and DSA. CT-angiography was performed under standardized
      parameters and included processing with 3D surface reconstructions. RESULTS: In
      64 patients (60.4%) a total of 72 aneurysms were detected. In four cases (6.2%)
      there were two and in two cases (3.1%) even three aneurysms. The findings of DSA
      and CTA agreed in 98 cases (92.5%). In four patients (3.8%) a false negative
      result was obtained in CTA and the initial DSA. CONCLUSIONS: Digital subtraction
      angiography must still be considered as the gold standard in the diagnosis of
      cerebral aneurysms. On account of its excellent spatial delineation of aneurysms
      and possibilities for exact measurements, CT-angiography represents a valuable,
      supplementary method--in some cases also an alternative method--to digital
      subtraction angiography.

PMID- 9592580
TI  - [Does angiographic localization of bleeding affect the management and mortality
      in gastrointestinal hemorrhage of unknown origin?].
AB  - PURPOSE: To evaluate the effect of angiography on patient management and
      mortality in patients with GIB of unknown origin. MATERIAL AND METHODS: 88
      angiographies were performed in 74 patients with GIB of unknown origin (18 upper
      gastrointestinal tract [GIT]), 35 lower GIT. 21 unknown localisation) and were
      evaluated retrospectively in regard to the influence on patient management and
      clinical outcome. RESULTS: After unsuccessful endoscopic diagnosis, angiography
      shows a sensitivity of 60% in the acute phase of GIB. Once the GIB had stopped
      the sensitivity was 14%. Following angiographic localisation, patients were more
      commonly treated surgically (71% vs. 44.5%) and subsequently had a lower rate of
      persistent or recurring bleeding (15% vs. 37.5%) as well as a lower event related
      mortality (10.5% vs. 25%). Patients with angiographic localisation of the
      bleeding site had a better outcome than patients with unsuccessful bleeding
      localisation, with regard to both surgical (85% vs. 62.5%) and conservative (100%
      vs. 85%) treatment. CONCLUSION: Angiographic localisation should be attempted in
      all cases of unknown GI-bleeding after endoscopic methods have been unsuccessful
      or ambiguous, because such a procedure has a positive effect on patient
      management and outcome. Moreover, angiography also offers therapeutic options.

PMID- 9592581
TI  - [PTA of the brachiocephalic arteries].
AB  - PURPOSE: Assessment of the technical success and mid-term success of PTA of
      brachiocephalic occlusive disease. MATERIAL AND METHODS: 24 patients, who were
      treated interventionally because of stenoses of the brachiocephalic arteries were
      enrolled into this prospective study. In total there were 27 lesions (26
      arteriosclerotic lesions and one dissection with pseudoaneurysma). 18 lesions
      were located in the subclavian artery (extending into the axillar artery in one
      case), 4 in the brachiocephalic trunk, three in the common carotid artery and two
      in the vertebral artery. As adjunctive to balloon dilatation 8 stents were
      implanted. RESULTS: Technical success was achieved in 24/27 lesions. There was an
      embolic complication in one of 27 interventions. 15/24 patients with 17 treated
      lesions underwent control angiography with a mean follow-up of 14 months. Follow
      up angiography revealed one occlusion and three significant restenoses. 5/24
      patients agreed only to clinical follow-up and Doppler examinations, three were
      lost and one patient died. CONCLUSION: PTA of brachiocephalic occlusive disease
      showed good technical success. Additional implantation of stents may be useful.
      Midterm success is satisfactory.

PMID- 9592582
TI  - [Possibilities of follow-up imaging after implantation of a carbon fiber
      reinforced hip prosthesis].
AB  - INTRODUCTION: There are many problems in the radiological diagnosis of aseptic
      loosening in total hip arthroplasty. Computed tomography (CT) and magnetic
      resonance tomography (MRT) are not usable for metallic implants (stainless steel,
      cobalt alloy, titanium alloy). MATERIAL AND METHODS: From April 1993 to December
      1993 15 CFRP non-cemented hip prostheses have been implanted. In a prospective
      clinical study plane radiographs, CT and MRT have been analysed. RESULTS: Three
      stems were revised (1 femoral fracture, 1 severe thigh pain, 1 aseptic
      loosening). CFRP are not visible in plane radiographs. There was a complete (two
      third of the cases) or nearly complete (one-third of the cases) small sclerotic
      interface between the prosthesis and the bone, these were apparent in CT and MRT
      in stable implant cases and did not have any clinical correlations. DISCUSSION:
      The small sclerotic interface is quite different in comparison to so called
      "Reactive Lines". In one case of aseptic loosening there was an interposition of
      soft tissue between prosthesis and bone in MRT and CT. CFRP inaugurates new
      diagnostic possibilities in aseptic loosening of hip prosthesis and in tumour
      surgery too.

PMID- 9592583
TI  - [Pulmonary complications of induction therapy in acute myeloid leukemia in
      adults. Findings in chest x-rays and computer tomography].
AB  - To exclude pulmonary complications, 359 chest radiographs and 50 computed
      tomographs of the lung were performed in 95 patients suffering from acute myeloid
      leukemia. The radiological findings were registered, described and correlated
      with clinical findings in the present study on 2395 days of observation. RESULTS:
      In summary, 52 patients showed alterations of the lung. Pulmonary hyperhydration
      was seen in 21 cases, bacterial pneumonia was found in 18 cases, invasive
      pulmonary aspergillosis was documented in 14 cases, and 5 cases of severe
      haemorrhage were seen. An unexplained pulmonary edema in 13 patients with
      interstitial and alveolar infiltrates is considered to be a complication of
      treatment with cytosine- arabinoside. CONCLUSION: The results demonstrate that
      chest X- ray and computed tomography have a high impact in detection and
      treatment of pulmonary complications following intensive chemotherapy. We may
      expect the development of diffuse opacity following administration of cytosine
      arabinoside in medium-sized doses.

PMID- 9592584
TI  - [Solid craniopharyngioma in the 3rd ventricle--differential diagnostic aspects].
AB  - We report on a 54-year-old man with a solid craniopharyngioma in the third
      ventricle. Differentiation from a meningeoma was possible by visualization of a
      small cystic component in the suprasellar cistern and a central hypodensity/
      hypointensity on CT and MRI, respectively. The latter seems to be a rather
      typical finding. Considering the differential diagnosis of tumors within the
      third ventricle, it must be emphasized that tumors arising within the ventricle
      are rare and invasion from primary extraventricular tumors is more common. A
      craniopharyngioma of the papillary type often has the typical imaging appearance
      described above.

PMID- 9592585
TI  - [Long-term follow up of intravenous mercury therapy].
AB  - In the case of an intravenous mercury injection, the mercury can be seen in the
      right heart, the lungs, the liver, and the kidney, but seldom in the spleen, the
      extremities, and the vertebral canal. In the subsequent period there is a
      distribution of the mercury and clinical symptoms will show the toxicity of the
      metal. We describe a patient with a follow-up time of 19 years, from the
      radiological point of view.

PMID- 9592586
TI  - [Aortic rupture and retroperitoneal bleeding im Behcet disease].
AB  - Although retroperitoneal hemorrhage is a rather seldom complication of Behcet's
      syndrome it is in no way unusual. Younger patients in particular those from the
      eastern Mediterranean or east Asian regions in whom a retroperitoneal hemorrhage
      or an aneurysm in the aorto-iliaco-femoral flow region has be diagnosed must be
      considered for the differential diagnosis of Behcet's syndrome. The consequences
      for the surgeon are resection deep into healthy tissue and in general an
      appropriately close follow-up with strict avoidance of arterial angiography.

PMID- 9592588
TI  - Modulation of cerebral cortex in acupuncture stimulation: a study using
      sympathetic skin response and somatosensory evoked potentials.
AB  - Although acupuncture has been widely used for treating disorders, its therapeutic
      mechanism remains unclear. In order to study the physiological mechanism of
      acupuncture stimulation, both palm recordings of sympathetic skin response (SSR)
      were evoked by electrical stimulation of the right median nerve on 13 normal
      adult volunteers. Median nerve evoked short-latency somatosensory evoked
      potential (SEPs) recordings were taken at least one week after SSR recording. The
      latencies and amplitudes were calculated. N13 component was obtained from Cv7,
      and N20 and P25 were from somatosensory cortex. The control did not receive
      acupuncture stimulation. Acupuncture needles were inserted into both Zusanli (St
      36) acupoints as follows: 1) manual acupuncture (MA): using fingers to twist the
      acupuncture needle until so-called Der-Qi was obtained, 2) 2 Hz
      electroacupuncture (EA): 2 Hz square-wave electrical pulses were applied between
      the Zusanli needle and the Shangjuxu (St-37) needle bilaterally. Our results
      indicated that the mean latencies of SSR were largest during 2 Hz EA followed by
      MA stimulation, whereas the period of control exhibited the shortest mean
      latencies. In contrast, the mean amplitudes of SSR were smallest during the
      period of 2Hz EA, followed by the period of MA, and the period of control
      exhibited the largest mean amplitudes of SSR. The latencies of N13, N20 and P25
      remained unchanged, but the amplitudes of P25 were largest during the period of
      2Hz EA, followed by the period of MA; the period of control exhibited the
      smallest mean amplitudes of SEPs. The results suggest that acupuncture
      stimulation of both Zusanli acupoints inhibited SSR, which implies that the
      cerebral cortex contributed at least in part to this inhibition. The stimulation
      effect of 2Hz EA is stronger than MA.

PMID- 9592587
TI  - [Splenic echinococcosis--a rare differential diagnosis in a cystic lesion of the
      spleen].
AB  - Cystic tumours of the spleen are generally rare and a parasitic origin is
      relatively improbable. Our case report, however, shows that in case of a splenic
      cyst, differential diagnosis must always consider the possibility of
      echinococcosis. We report on a patient suffering from a cystic lesion of the
      spleen where radiology yielded the final pointer to diagnosing an echinococcosis
      of the spleen.

PMID- 9592589
TI  - Comparison of substance P concentration in acupuncture points in different
      tissues in dogs.
AB  - Histologically, acupuncture points show neuronal innervation. One hundred seventy
      seven tissue samples of acupuncture points and control points from 4 dogs were
      collected. Concentrations of substance P, a neurotransmitter, in the skin, muscle
      and subcutis of acupuncture points and control points were measured by means of
      enzyme immunoassay. The determined tissue concentrations of substance P (mean +/-
      SEM) in acupuncture points and control points were 1.81 +/- 0.13 and 1.51 +/- 0.1
      ng/g in the muscle, 3.33 +/- 0.29 and 2.63 +/- 0.28 ng/g in the skin and 1.59 +/-
      0.22 and 1.32 +/- 0.16 ng/g in the subcutis, respectively. The results indicate
      that there is a difference in the neurochemical profile between acupuncture
      points and control points.

PMID- 9592590
TI  - Topography of low skin resistance points (LSRP) in rats.
AB  - Based on the electrical properties of the skin, a method employing the
      unijunction transistor (UJT) relaxation oscillator for detecting low skin
      resistance points (LSRP) was developed in this study. By means of this
      instrumentation, the topography of the LSRP in Wistar rats was developed. All the
      LSRP in the rats were found to be bilaterally and symmetrically distributed
      except those points located on the dorsal midline (i.e., governor vessel, GV) and
      the ventral midline (i.e., conception vessel, CV). The resistances of the LSRP on
      these two major vessels, including 14 CV points and 17 GV points of six rats were
      experimentally determined to be in the ranges of 179.4 +/- 41.2 K omega and 152.5
      +/- 32.2 K omega, respectively. The resistances of the GV points were found in
      general to be lower than those of the CV points. Most non-LSRP, on the other
      hand, exhibited resistances of greater than 420 K omega. It is noted that the
      resistances of most LSRP increased yet still retained a separate identity within
      thirty minutes after the death of the animals, but the low resistance properties
      of some LSRP gradually disappeared thereafter and could not be detected by the
      relaxation oscillator.

PMID- 9592591
TI  - Effects of moxibustion on the enhancement of serum antibody in rabbit against
      Staphylococcus aureus.
AB  - The titer and activity of antibody in rabbits immunized with heat-killed vaccine
      were assessed with and without moxibustion treatment. Enzyme-linked immunosorbent
      assay (ELISA) was applied for the detection of immunoglobulins to Smith strain of
      Staphylococcus aureus. Positive IgM titer of more than 0.4 were observed with
      this assay against the moxibustion group (P < 0.05). The titer of IgG antibody
      also increased; however, there was no significant difference between the
      moxibustion group and the control group. The ELISA inhibition test showed
      significantly higher protective activity of the sera in the moxibustion group at
      the 9th week after the first immunization (P < 0.05).

PMID- 9592592
TI  - Absence of an analgesic effect of qigong "external qi" in rats.
AB  - The analgesic effect of "external Qi" emitted from the Qigong practitioner was
      investigated in rats. In behavioral experiments, the rat's tail-flick and head
      movement threshold measurements were used to determine if the "external Qi" had
      analgesic effect. The results were negative. In electrophysiological study, the
      "external Qi" shows no significant changes in the pain-related evoked cortical
      potentials to tooth-pulp stimulation. Thus the results of this study are
      different from those reported by other investigators. It is proposed that this
      research be repeated and extended.

PMID- 9592593
TI  - Gut and brain effects of American ginseng root on brainstem neuronal activities
      in rats.
AB  - Brainstem neurons receiving subdiaphragmatic vagal inputs were recorded in an in
      vitro neonatal rat brainstem-gastric preparation. Aqueous extracts of American
      ginseng root (Panax quinquefolium L.) were applied to the gastric compartment or
      the brainstem compartment of the bath chamber to evaluate the peripheral gut and
      central brain effects of the extracts on brainstem unitary activity. After Panax
      quinquefolium L. application to the gastric or brainstem compartment, a
      concentration-related inhibition in neuronal discharge frequency in the brainstem
      unitary activity was observed, suggesting that Panax quinquefolium L. may play an
      important role in regulating the digestive process and modulating brain function.
      In this study, pharmacological effects of American-cultivated Panax quinquefolium
      L. and Chinese-cultivated Panax quinquefolium L. were also compared. Our results
      suggest that American-cultivated Panax quinquefolium L. possesses a significantly
      stronger gastric modulating effect on brain neuronal activity.

PMID- 9592594
TI  - Inhibitory effect of shofu-san, a Japanese kampo medicine, on neutrophil
      functions in vitro.
AB  - The effect of Shofu-san (TJ-22), an oral Japanese kampo medicine, on several
      inflammatory parameters of human neutrophils, including reactive oxygen species
      (ROS) generation, chemotaxis, and calcium concentration, [Ca2+]i in neutrophils
      was examined in vitro. In addition, ROS generated in a cell-free, xanthine
      xanthine oxidase system was also assessed. The species investigated were
      superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical
      (OH.). TJ-22 significantly decreased neutrophil-generated O2-, H2O2 and OH. in a
      dose-dependent manner. The medicine also markedly inhibited neutrophil chemotaxis
      and [Ca2+]i in neutrophils. In addition, three kinds of ROS generated in the cell
      free system was reduced in the presence of TJ-22. Our results indicate that TJ-22
      may exert an anti-inflammatory action by inhibiting the neutrophil functions and
      scavenging ROS, leading to a reduction in oxidative tissue injury.

PMID- 9592595
TI  - Prevention of ethanol-induced gastric lesions in rats by wu-bei-san.
AB  - The effects of Wu-Bei-San (WBS) and its components Wu-Tsi-Ku (WTK) and Bei-Mu
      (BM) on gastric lesions induced by necrotizing agents were investigated in rats.
      Oral administration of WBS or WTK, but not BM, dose-dependently prevented gastric
      lesions induced by ethanol. Moreover, the gastric protective action of WTK was
      potentiated by simultaneous administration of BM under the same experimental
      conditions. Pretreatment with indomethacin, which is a prostaglandin synthesis
      inhibitor and idoacetamide, which is a sulfhydryl blocker did not influence the
      inhibited ethanol lesion of WBS. Gastric lesions induced by acidified aspirin
      were prevented by both WBS and calcium carbonate, which is a major constituents
      of WTK. However, pretreatment with calcium carbonate did not affect the gastric
      lesions induced by ethanol. These results indicate protective action of WBS on
      the gastric mucosa through both acid neutralization and cytoprotection, although
      more work is needed to clarify the role of WBS in cytoprotection.

PMID- 9592596
TI  - Liu-wei-dihuang: a study by pulse analysis.
AB  - Pulse analysis method was used in studying the traditional Chinese formula Liu
      Wei-Dihuang as well as five of its main components (Rehmannia glutinosa, Cornus
      officinalis, Paeonia Suffruticosa, Poria cocos and Alisma plantogo-aquatica var
      oriental). Based on our recently developed resonance theory, we tried to
      elucidate the mechanism and mutual reactions of these meridian related herbs. Hot
      water herbal extracts were injected intraperitoneally into rats and the pressure
      pulse spectrum at the caudate artery was measured. The results of this study
      indicated that Liu-Wei-Dihuang mildly increased blood flow to meridians with
      lower resonance frequency: namely the liver C1, the kidney C2 and the spleen C3;
      but decreased blood flow to the higher resonance frequency organs and meridians:
      the lung C4, the stomach C5, the gall bladder C6, and the bladder C7. It also
      decreased the heart load C0. All of the five herb components increased blood flow
      to the kidney C2 and the spleen C3; but their effects on the high frequency
      organs varied. Alisma plantogo-aquatica var. oriental decreased the C0, C5, C6,
      C7; Poria cocos decreased C1, C4, C5, C6; Rehmannia glutinosa, Paeonia
      Suffruticosa decreased C0, C4, C5, C6, C7; Cornus officinalis increased C4 but
      decreased C0, C5, C6, C7.

PMID- 9592597
TI  - Effects of Chinese herbal prescriptions on copulatory activity in aged male rats:
      a preliminary study.
AB  - Four herbal prescription medicines, Chi-Pao-Mei-Jan-Tan, Gui-Fu-Ba-Wei-Wan, Huan
      Shao-Tan; and San Tsai-Feng-Sui-Tan, were tested for their effects on sexual
      behavior in aged rats. Crude liquid extracts of these herbs were administered to
      the rats daily through oral tubing for 14 days. All four herbal prescriptions
      showed some effects in restoration of mount and intromission behaviors, but there
      was no effect on restoration of ejaculation in 26 month old rats that had
      exhibited no copulatory activity (no mount, intromission and ejaculation)
      previously. The effects of Chi-Pao-Mei-Jan-Tan were further tested in 26 month
      old rats with low mount and intromission activities but without ejaculation
      behavior, and in 15 month old rats (middle-age group) that showed normal mount
      and intromission behavior but no ejaculation activity. Chi-Pao-Mei-Jan-Tan was
      effective in improving the frequency of both mount and intromission, but failed
      to restore the ejaculation activity of the old rats with low mount and
      intromission behaviors. It was, however, very effective in restoration of
      ejaculation activity in middle-aged rats that exhibited normal mount and
      intromission behaviors. Serum testosterone (T) levels of Chi-Pao-Mei-Jan-Tan in
      tested old and middle-aged rats were determined by radioimmunoassay, and showed
      no difference before and after treatment. Our findings demonstrated that the four
      herbal prescriptions had some effects in restoration of mount and intromission
      behaviors, but not ejaculation activity in old rats, and that Chi-Pao-Mei-Jan-Tan
      was very effective in restoration of ejaculation activity in middle-aged rats.
      The promotional effect of Chi-Pao-Mei-Jan-Tan on copulatory behavior was not
      correlated with serum T levels.

PMID- 9592598
TI  - Response of healthy individuals to ninjin-yoei-to extract--enhancement of natural
      killer cell activity.
AB  - After administering 15 g/day of Ninjin-Yoei-To (NYT) for one week to healthy
      people whose NK activity had already been increased by physiological response, a
      further increase in NK activity was observed after two days. This increased level
      of NK activity continued during the administration of NYT for a one-week period.
      The maintaining and reinforcing effect on the immune surveillance system by NYT
      may be useful for prevention of carcinogenesis.

PMID- 9592599
TI  - Raffinee, a free radical scavenger, in the treatment of subacute stage brain and
      spinal cord lesions: a case report.
AB  - This report presents the effects of the natural antioxidant formulation
      "Raffinee" in treatment of a case with subacute cerebellar hemorrhage and a case
      with subacute incomplete cervical cord injury. Four days after onset of
      cerebellar hemorrhage, the regimen started and ameliorated severe headache and
      dizziness within 3 days. Forty-five days after incomplete spinal cord injury with
      marked edema of cervical cord, the regimen started. Excellent motor and sensory
      function recovery were obtained within one month with remission of cord edema.
      The dosage of "Raffinee" is equivalent to 2,280,000 units of superoxide radical
      scavenging activity and 47,000 units of hydroxyl radical scavenging activity.
      Based on the secondary injury theory, superoxide and hydroxyl radical scavengers
      may have a valuable use in subacute central nervous system (CNS) lesions. Further
      larger scale of randomized, placebo-controlled, double-blind clinical trials are
      indicated to verify the effect of "Raffinee" on subacute CNS lesions.

PMID- 9592600
TI  - Consumer literature on alternative medicine: addressing consumer confusion.

PMID- 9592601
TI  - What every perioperative nurse should know about customers.

PMID- 9592602
TI  - Video-assisted thoracoscopic discectomy and fusion.
AB  - Anterior discectomies and fusions are performed on patients who have anteriorly
      herniated discs. Fusions are accomplished using bone grafts harvested from the
      patient or by using cadaveric bone grafts that are inserted into the disc space
      for stability. This procedure traditionally has been performed through an open
      incision, but now can be accomplished using a video-assisted thoracoscope. The
      benefits of this minimally invasive technique for patients include decreased
      blood loss, less postoperative pain, and a shorter hospital stay.

PMID- 9592603
TI  - Advances in endoscopic neurosurgery.
AB  - This article describes the authors' experience using neuroendoscopes to perform a
      variety of intracranial procedures with minimal invasiveness to neural tissue.
      The article also presents the history of neuroendoscopy and provides information
      about current practice. Surgical technique and intraoperative and postoperative
      nursing considerations are reviewed.

PMID- 9592604
TI  - Are all sterilization processes alike?
AB  - Automated processes designed to sterilize reusable medical instruments use heat
      and low-temperature chemicals. Several factors, including the physical properties
      of the sterilizing agents and whether all of the instruments' surfaces can be
      adequately cleaned, can cause significant variations in the reliability and
      effectiveness of the sterilization processes. Instruments exposed to heat-based
      sterilization processes pose the lowest probability of transmitting diseases
      between patients. Heat can conduct through many different types of materials and
      can destroy microorganisms embedded under layers of patient debris. Studies have
      demonstrated, however, that--unlike heat--low-temperature chemicals require
      direct contact with the microorganisms to be effective. Moreover, the complex
      designs of some instruments can adversely affect the low-temperature
      sterilization processes' outcomes by hindering cleaning and preventing the flow
      of low-temperature chemicals to all of the instruments' contaminated surfaces.
      This article will explore the differences between heat-based and low-temperature
      chemical processes to help health care providers minimize the risk of cross
      infection.

PMID- 9592605
TI  - A study of patterns and prevention of blood exposures in OR personnel.
AB  - The authors conducted a surveillance study of occupational blood exposures in the
      ORs at six hospitals to identify risk patterns and prevention strategies. For 15
      months, trained circulating nurses recorded OR staff members' exposures during
      all surgical procedures using a modified version of the Exposure Prevention
      Information Network surveillance system. It was discovered that a high proportion
      of percutaneous injuries were potentially preventable if safer devices had been
      used, and the authors estimate that use of blunt suture needles alone could
      reduce injuries by 30%. Increased use of barrier precautions is indicated to
      prevent mucocutaneous blood exposures. Health care workers' eyes were identified
      in the study as being the most vulnerable location for serious blood exposures.

PMID- 9592606
TI  - The evolving role of advanced practice nurses in surgery.
AB  - Health care reform has created many opportunities for advanced practice nurses
      and for OR nurses who want to go beyond traditional circulating and scrub roles.
      This article will briefly differentiate between expanded and advanced nursing
      practice and offer a definition and conceptual model for the surgical arena.
      Literature will be reviewed related to development, evaluation, and practice
      issues of the emerging role of the surgical advanced practice nurse.

PMID- 9592607
TI  - Postoperative education that works.
AB  - Perioperative nurses have acquired greater responsibility for patients' and
      family members' postoperative education. Recent nursing research indicates that
      patients may not be getting specific information about dealing with the everyday
      practical matters they encounter while recovering at home from their surgical
      procedures. This article addresses some of these issues (e.g., food, sex,
      driving, bathing, wound care, return to work, limits on activities). The authors
      answer questions most often asked by patients and their family members.

PMID- 9592608
TI  - The future of robotics can be ours.
AB  - As the use of robotic aides increases the possibility of telesurgery, the
      perioperative scope of practice could include using patients' homes or other
      nontraditional settings as surgical sites. Even mobile surgical vans could be
      used. To perform telesurgery, the health care industry actively must define the
      role of the health care professional with the patient who can make an incision
      and insert a laparoscope. This may create an opportune time to promote the RN
      first assistant (RNFA) role--a goal that will involve expanding our state nurse
      practice acts to allow RNFAs to perform various functions for true advanced
      practice in nontraditional settings. Additionally, it will mean defining what
      functions and personnel must be available in these new creative settings. Current
      experiments have focused on using nonlicensed assistants, which can lead to legal
      and moral concerns. Legal and moral concerns include not only appropriate
      personnel, but also patient privacy. In telesurgery, patient information would be
      transmitted over communication lines, possibly seriously jeopardizing patient
      privacy. Perioperative nurses must be vigilant regarding patient privacy and
      continue to be patient advocates. Additional concerns relate to the possible
      complications or emergencies that can occur in any procedure, such as bleeding,
      cardiac arrest, or malignant hyperthermia. As this field is being developed,
      these concerns must be addressed, and possible complications and emergencies must
      be prepared for. All patients deserve highly trained individuals to care for
      them. It is a concern that unlicensed personnel are being considered to manage
      these potentially serious situations. It is now more important than ever that
      perioperative nurses stay on top of technologic advances. One surgeon stated that
      perioperative nurses are at a point in history in which they can make a
      difference--a potentially lifesaving difference. Nurses will have to be
      comfortable with new technology, know when it is working well, and be able to
      assess the patient's status critically. The use of robotic aides can decrease the
      amount of physical work that nurses do; however, they also have the capability to
      denigrate nurses' positions. If not careful, nurses could lose their focus on the
      caring aspect of the nursing profession. Although computers remain machines
      programmed by humans, it seems they more often are masters of information. Today,
      procedures can be performed in cyberspace as if surgeons were present at the
      surgical sites. Could robotic aides and computers do a better job than physicians
      and nurses, causing these health care providers to become extinct? Probably not.
      Although robots and computers may be able to replicate the knowledge and skill of
      physicians, patients require human interaction that computers cannot provide.
      This involves feelings and human communication beyond current technology, despite
      robotic engineers' continuing attempts to replicate this. The ultimate use of
      robotics remains uncertain; however, the human touch will not soon, if ever, be
      replaced by robotic technology. It is now of utmost urgency that all
      perioperative nurses refine and hone the caring skills that Florence Nightingale
      instilled to ensure their professional future. Robotics is a new and challenging
      aspect being added to nursing care. Nurses must take an active role, embrace this
      technology, and work to maximize their position with it.

PMID- 9592609
TI  - The advocate "on call".

PMID- 9592610
TI  - The "essentials" of an effective corporate compliance program.

PMID- 9592611
TI  - Developing clinical practice guidelines as an approach to evidence-based
      practice.

PMID- 9592612
TI  - Developing a pediatric patient/parent hospital preparation program.

PMID- 9592613
TI  - Measuring vitamin A in blood plasma and serum.

PMID- 9592614
TI  - An ethicist's commentary on the case of the elderly client seeking "unnecessary"
      medical advice.

PMID- 9592615
TI  - Examination of the thoracic cavity and lung lobectomy by means of thoracoscopy in
      dogs.
AB  - The feasibility of thoracoscopy for viewing the chest cavity and performing
      pulmonary lobectomy was assessed in 8 mongrel dogs. Previously, selective
      intubation had been performed in another group of dogs (n = 8) in order to
      monitor respiratory physiology and assess its safety. Each hemithorax was
      intubated using a double-barrelled endotracheal tube with one barrel placed in
      the left main bronchus and the other in the bifurcation of the trachea. The
      thoracoscope was introduced through a cannula inserted through a 2-cm incision at
      the ventral third of the left 5th intercostal space. The cranial, dorsal, and
      caudal surfaces of the pleura, lobes of the left lung, and the mediastinum were
      examined. A 2nd cannula was located in the dorsal 3rd of the 5th intercostal
      space with a prior incision and used for the introduction of forceps to separate
      the viscera. To biopsy, a 3rd cannula was inserted at the dorsal third of the 8th
      intercostal space with a prior incision, through which a 12-mm diameter stapler
      was introduced. Should a lobectomy be necessary, a 4th cannula is located in the
      middle third of the 4th intercostal space. Excision of the left caudal pulmonary
      lobe was performed through the incision made for the 12-mm diameter cannula (8th
      intercostal space); a twisting movement facilitated removal. Thoracoscopy is a
      procedure that can be used in dogs and is particularly suitable for examination,
      collection of biopsy specimens, and even lung lobectomies.

PMID- 9592616
TI  - Copper deficiency in a herd of captive muskoxen.
AB  - At necropsy, a mature muskox cow was found to have exceedingly low serum and
      liver copper concentrations of 4.8 = mumol/L and 0.02 mmol/kg, respectively.
      Serum copper levels were also low in remaining members of the herd but returned
      to normal after parenteral treatment with calcium copper edetate.

PMID- 9592617
TI  - Probable ceftiofur-induced cutaneous drug reaction in a cow.
AB  - A cow with pyelonephritis was treated with ceftiofur (3 mg/kg body weight, IV,
      q12 h). Hair loss and pruritus were observed after 8 and 12 d of treatment,
      respectively. Ancillary laboratory tests supported a diagnosis of allergic
      disease. Clinical signs and laboratory test results normalized after ceftiofur
      administration was stopped.

PMID- 9592618
TI  - Topiramate. Clinical profile in epilepsy.
AB  - Topiramate, a sulfamate-substituted monosaccharide, is a new antiepileptic drug
      (AED) approved as adjunctive therapy for partial-onset seizures in adults.
      Topiramate is rapidly absorbed, has linear pharmacokinetics, minimal protein
      binding and a long half-life facilitating a twice-daily dosage regimen.
      Topiramate has little effect on the plasma concentrations of other AEDs with the
      exception of phenytoin, concentrations of which may increase in some patients
      when topiramate is added to the therapy. Topiramate metabolism is increased when
      administered with carbamazepine or phenytoin. In the absence of enzyme-inducing
      AEDs, topiramate is eliminated primarily by renal excretion, with 50 to 80% of a
      dose excreted as unchanged topiramate. In 6 double-blind, placebo-controlled
      trials, topiramate was shown to be well tolerated and effective as adjunctive
      therapy for partial-onset seizures in adults. Topiramate consistently reduced
      seizures across all patient groups defined by age, gender and baseline seizure
      frequency. Adverse effects were generally mild-to-moderate CNS-related effects
      and often resolved spontaneously or with slowing of topiramate titration and/or
      reduction of the dosage of concomitant AEDs. Clinical studies are currently
      evaluating the effectiveness and safety of topiramate as monotherapy and
      adjunctive therapy in children with partial seizures, in patients with Lennox
      Gastaut syndrome and in patients with generalised tonic-clonic seizures of non
      focal onset. Preliminary findings suggest that topiramate has a broad spectrum of
      clinical use.

PMID- 9592619
TI  - Pharmacokinetics and pharmacodynamics of hydroxyurea.
AB  - Hydroxyurea is used in the treatment of various forms of cancer, sickle-cell
      anaemia and HIV infection. Oral absorption of the drug is virtually complete, the
      volume of distribution is equivalent to total body water and elimination is
      through both renal and nonrenal mechanisms. Nonrenal elimination of hydroxyurea
      is characterised by Michaelis-Menten kinetics. Further studies are necessary to
      clarify several aspects of the pharmacokinetics and pharmacodynamics of
      hydroxyurea: the effect of age and disease state, concentration-effect
      relationship, the role of therapeutic drug monitoring, and the mechanisms of
      renal and nonrenal elimination. The recent development of improved assays for
      hydroxyurea should have benefits for future pharmacokinetic studies.

PMID- 9592620
TI  - The aging liver. Drug clearance and an oxygen diffusion barrier hypothesis.
AB  - A change in drug clearance with age is considered an important factor in
      determining the high prevalence of adverse drug reactions associated with
      prescribing medications for the elderly. Despite this, no general principles have
      been available to guide drug administration in the elderly, although a
      substantial body of clearance and metabolism data has been generated in humans
      and experimental animals. A review of age-related change in drug clearances
      established that patterns of change are not simply explained in terms of hepatic
      blood flow, hepatic mass and protein binding changes. In particular, the
      maintained clearance of drugs subject to conjugation processes while oxygen
      dependent metabolism declines, and all in vitro tests of enzyme function have
      been normal, requires new explanations. Reduction in hepatic oxygen diffusion as
      part of a general change in hepatocyte surface membrane permeability and
      conformation does provide one explanation for the paradoxical patterns of drug
      metabolism, and increased hepatocyte volume would also modify oxygen diffusion
      path lengths (the 'oxygen diffusion barrier' hypothesis). The reduction in
      clearances of high extraction drugs does correlate with observed reduction in
      hepatic perfusion. Dosage guidelines emerge from these considerations. The dosage
      of high clearance drugs should be reduced by approximately 40% in the elderly
      while the dosage of low clearance drugs should be reduced by approximately 30%,
      unless the compound is principally subject to conjugation mechanisms. If the
      hepatocyte diffusion barrier hypothesis is substantiated, this concept may lead
      to therapeutic (preventative and/or restorative) approaches to increased
      hepatocyte oxygenation in the elderly. This may lead to approaches for
      modification of the aging process in the liver.

PMID- 9592621
TI  - Drug interactions at the renal level. Implications for drug development.
AB  - The kidney plays a major role in the elimination of drugs. The purpose of this
      paper is to: (i) review the mechanisms of renal elimination; (ii) identify
      potential mechanisms for renal drug interactions; (iii) review in vitro and in
      vivo animal models for studying renal elimination mechanisms and identifying
      potential drug-drug interactions; (iv) review experimental designs used in
      identifying drug-drug interactions in humans with an emphasis on gaining
      information regarding the mechanism of the interaction; and (v) make
      recommendations regarding the potential for renal drug interactions in drug
      development. It is concluded that clinically significant drug interactions
      resulting in toxicity because of some mechanism at the renal level appear to be
      relatively rare and that in vitro screening should not be done on all drugs
      during drug development. Five potential mechanisms exist for drug interactions at
      the renal level: (i) a displacement of bound drug resulting in an increase in
      drug excretion via an increase in glomerular filtration; (ii) competition at a
      tubular secretion site resulting in a decrease in drug excretion; (iii)
      competition at the tubular reabsorption site resulting in an increase in drug
      excretion; (iv) a change in urinary pH and/or flow that may increase or decrease
      drug excretion depending on the pKa of the drug; and (v) inhibition of renal drug
      metabolism. The most well known renal drug interaction is competitive inhibition
      of tubular secretion, ultimately leading to an increase in plasma drug
      concentration. Only when renal clearance is a major contributor to the total
      clearance (> 30%) and plasma concentrations are greater than the Michaelis-Menten
      transport constant does the potential exist for clinically significant renal drug
      drug interactions because only then does nonlinear pharmacokinetics become
      evident. The potential for drug interactions is small when renal clearance is
      less than 20 to 30% of the total clearance and/or when plasma concentrations are
      less than the Michaelis-Menten transport constant, unless the drug has a narrow
      therapeutic window.

PMID- 9592623
TI  - Metabolism of fibric acid derivatives.

PMID- 9592622
TI  - Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate
      cancer.
AB  - Prostatic cancer is the second most common cause of cancer death in males.
      Treatment by radical prostatectomy and radiotherapy is useful in the early stages
      of the disease. Whenever metastases occur, patients are usually treated by
      surgical (orchidectomy) or medical [gonadotropin releasing hormone (GnRH)
      analogue] castration. This form of treatment is, however, associated with
      unwanted adverse effects, such as flushing, loss of libido and potency and all
      patients ultimately escape therapy after a delay of 1 to 2 years. For this reason
      antiandrogens have been developed as another means of endocrine ablation therapy.
      Antiandrogens fall in 2 groups of which the first group, the steroidal
      antiandrogens such as cyproterone acetate (CPA), have a direct blocking effect at
      the cellular level but also inhibit testosterone production by their additional
      gestagenic properties blocking gonadotropin secretion. Except in preventing the
      flare-up associated with the start of GnRH analogue therapy and in reducing
      flushing, no evidence exist of any superiority for CPA over classical therapy in
      terms of adverse effects and survival. The second group, the nonsteroidal or
      'pure' antiandrogens, only block androgens at the cellular level without any
      central effects. In contrast with other forms of castration, patients on pure
      antiandrogens as monotherapy preserve their sexual function and potency, at the
      expense of a slightly inferior androgen blockade and gynecomastia. These latter
      effects are explained by a compensatory rise in androgens as a result of the
      blockade at the central level, which weakens the androgen blockade, and by
      peripheral aromatisation of the increased androgens to oestrogens. In addition,
      some evidence exist that pure antiandrogens improve survival if combined with
      other forms of castration as they also inhibit the adrenal androgens, the so
      called maximal androgen blockade (MAB). If patients escape control under MAB, a
      trial of stopping the antiandrogen must always be considered, as some tumours
      have 'learned' to be activated by these drugs. At the moment it is not yet clear
      if antiandrogens are of any benefit in downstaging the extent of disease before
      prostatectomy and/or radiotherapy. Of the currently known pure antiandrogens,
      bicalutamide offers some advantages over flutamide as it possesses a much longer
      half-life, allowing a once daily regimen, and has advantages over nilutamide in
      terms of fewer adverse effects.

PMID- 9592624
TI  - Growth factors and the kidney in diabetes mellitus.
AB  - Nephromegaly and mesangial matrix expansion observed in the diabetic kidney are
      all clues of a role of growth factors in the pathogenesis of these lesions. A
      growing body of evidence shows that changes in (1) insulin-like growth factor I
      regulation, and (2) the transforming growth factor beta loop exist in the kidney
      in the diabetic hypertrophic kidney and in diabetic glomerulosclerosis. However,
      other growth factors may be involved in some diabetic renal changes. The
      abnormalities in growth factor content and regulation, the role of growth factors
      in the diabetic kidney, and the effect of hyperglycemia and advanced
      glycosylation end products on growth factors in the kidney are reviewed.

PMID- 9592625
TI  - Pathogenesis of idiopathic calcium nephrolithiasis: update 1997.
AB  - Idiopathic calcium nephrolithiasis (ICN) is a frequent disease in Western
      countries. The physicochemical theory of lithogenesis, which explains stone
      formation by the precipitation, growth, and crystalline aggregation of lithogenic
      salts in the urine, has contributed greatly to the understanding of the
      pathogenesis of calcium urolithiasis. However, several aspects are still
      unexplained; the co-existence of familial occurrence, primary tubular
      dysfunctions with ICN, and anomalies in the systemic handling of oxalate and
      calcium led to the development of a cellular hypothesis of ICN. A number of
      cellular defects in the handling of ions has been reported that involves both
      anion and cation transport. These anomalies are probably the expression of a
      still unknown cellular defect in idiopathic calcium stone formers. We suggested
      that an anomaly in the cell membrane composition might be responsible for the
      complex array of cell ion flux abnormalities observed in ICN. Recently, a
      disorder in the n-6 polyunsaturated fatty acid series has been described; it is
      characterized by a lower linoleic acid content and a higher arachidonic acid
      concentration in both plasma and erythrocyte membrane phospholipids of renal
      calcium stone patients. This anomaly could cause an increased activity of ion
      carriers; furthermore, it may lead to increased prostaglandin synthesis and to
      secondary phenomena at the kidney, skeletal, and intestinal level. As a
      consequence, critical conditions for lithogenesis in the kidney may ensue. The
      data suggest a common pathogenesis for hypercalciuria and hyperoxaluria. The
      systemic defect in the phospholipid arachidonic acid level may be both of dietary
      or genetic origin; experimental data suggest that the increase in delta-6
      desaturase activity, the limiting enzyme in the metabolic pathway of
      polyunsaturated fatty acids, might be relevant to the pathogenesis of lipid
      abnormalities observed in nephrolithiasis and to the pathogenesis of ICN and its
      related problems (at the kidney, intestinal, and bone level).

PMID- 9592626
TI  - Use of nonionic block copolymers in vaccines and therapeutics.
AB  - Nonionic block copolymers synthesized from ethylene oxide and propylene oxide
      were developed specifically for use as surfactants. Because the sizes and
      relative positions of the hydrophobic polyoxypropylene (POP) and hydrophilic
      polyoxyethylene (POE) blocks can be altered during synthesis, copolymers with
      significantly different surfactant characteristics can be produced. Copolymers of
      this type are currently used as excipients in a wide variety of pharmaceutical
      products where they act as emulsifying, wetting, thickening, stabilizing, and
      dispersing agents. Copolymers with unique physicochemical properties have
      recently been developed through the use of new manufacturing and purification
      techniques, and these copolymers are being used as drug-active and drug-delivery
      components. In this review, we summarize the current status of these new
      copolymers in terms of research and product development. This includes the use of
      new, high molecular weight copolymers as vaccine adjuvants and as vaccine
      delivery vehicles. The use of purified, pharmaceutical-grade copolymers as anti
      infectives and as antibiotic-delivery systems for the treatment of established
      bacterial and viral infections is also reviewed. These novel uses for copolymers
      are significantly different from the excipient uses common to this type of
      product and demonstrate the widespread utility of synthetic surfactant polymers.

PMID- 9592627
TI  - From genes to gene medicines: recent advances in nonviral gene delivery.
AB  - Over the last decade, research in somatic gene therapy has focused on selected
      approaches to deliver therapeutic genes to cells both ex vivo and in vivo. While
      most current gene therapy clinical trials are based on cell- and viral-mediated
      approaches, nonviral gene medicines are emerging as potentially safe and
      effective in the treatment of a wide variety of genetic and acquired diseases.
      Nonviral technologies consist of plasmid-based expression systems containing a
      gene encoding a therapeutic protein and synthetic gene delivery systems. In
      addition to the therapeutic gene, plasmid-based expression systems contain other
      genetic sequences to control the in vivo production and secretion of a protein.
      They may include elements that prolong extrachromosomal gene expression, cell
      specific promoters and, optionally, gene switches for enabling drug-regulated
      gene therapy. Unique gene delivery systems will be required depending upon the
      biology and (patho)physiology of the target tissue. This review provides a
      critical view of gene therapy with a major focus on advanced nonviral
      technologies to control the in vivo location and function of administered genes.

PMID- 9592628
TI  - Epidemiology of DSM-III-R major depression and minor depression among adolescents
      and young adults in the National Comorbidity Survey.
AB  - Data on the prevalences, comorbidities, and cohort effects of DSM-III-R major
      depression (MD) and minor depression (mD) are reported for the nationally
      representative sample of n = 1,769 adolescents and young adults who participated
      in the National Comorbidity Survey. Lifetime prevalences are 15.3% (MD) and 9.9%
      (mD), while 30-day prevalences are 5.8% (MD) and 2.1% (mD). Most cases reported
      recurrent episodes (73.9% of those with MD and 69.2% with mD) and significant
      role impairment, including attempted suicide among 21.9% of those with MD. The
      majority of lifetime cases (76.7% of those with MD and 69.3% with mD) reported
      other comorbid lifetime NCS/ DSM-III-R disorders. Depression was temporally
      secondary in the majority of these cases. Number of prior disorders was more
      important than type of disorders in predicting subsequent depression, raising the
      possibility that secondary depression is a nonspecific severity marker for
      earlier disorders. A cohort effect for both MD and mD was documented that
      persisted even for episodes lasting a year or longer. Increasing prevalences of
      prior comorbid disorders were found to play an important part in explaining the
      cohort effect for depression.

PMID- 9592629
TI  - Adolescent depression: controlled desipramine treatment and atypical features.
AB  - The study was designed to test the efficacy of desipramine in adolescents with
      major depression (MDD). In addition, we assessed the presence of atypical
      features of MDD, consisting of mood reactivity and two of four associated
      features (rejection sensitivity, hyperphagia, hypersomnia, and leaden paralysis).
      Patients were randomized to desipramine (DMI) or placebo for 6 weeks, provided
      they failed to improve (e.g., meeting MDD criteria and a Hamilton Depression
      Scale score > or = 18) after 2 weeks on single blind placebo. Of 94 adolescents
      (ages 13-18) who were diagnosed as having MDD, 64 entered the study and 62
      received placebo for 2 weeks. Of these, 45 were randomized to DMI or placebo.
      Completed analyses did not reveal significant improvement for the active
      treatment compared to the placebo. A large proportion of adolescents responded to
      placebo (50%), suggesting the need for very large samples to detect differential
      treatment efficacy, should it exist. A relatively high rate of atypical
      depression was observed (47% in the 64 patients entered). In view of the
      demonstrated specificity of monoamine oxidase inhibitor efficacy in adults with
      atypical features of MDD, this clinical subtype may have relevance to future
      investigation of therapeutic interventions in adolescent MDD.

PMID- 9592630
TI  - Fluoxetine in child and adolescent depression: acute and maintenance treatment.
AB  - The objective was to present naturalistic 1-year follow-up information of 96
      child and adolescent outpatients with major depressive disorder who had been
      randomized in an 8-week double-blind, placebo-controlled trial of fluoxetine.
      Subjects were children and adolescents, ages 8-18 years, who were entered in a
      randomized clinical trial of fluoxetine. Following the acute treatment trial,
      treatment was not controlled. At 6 months and 1 year, the subjects and parents
      were interviewed using the Kiddie Longitudinal Interval Follow-up Evaluation (K
      LIFE) for course of depression. Eighty-seven of the 96 subjects were followed for
      1 year. Of these, 74 (85%) recovered from the depressive episode during that time
      (47 on fluoxetine, 22 on no medication, and 5 on other antidepressants or
      lithium). Twenty-nine of the subjects (39%) who recovered had a recurrence of
      depression during the 1-year follow-up, with 55% of these occurring within 6
      months. Results of this study are similar to adult studies, with respect to
      response and recovery of depressive episodes. Most patients (85%) recover from
      the episode within 1 year, but approximately 40% have a recurrence within 12
      months, which is a higher recurrence rate than in adults. Recovery was associated
      with younger age, lower severity of depressive symptoms, higher family
      functioning, and fewer comorbid diagnoses. Recurrence, which occurs both on and
      off medication, was difficult to predict, as there was little clinical data
      associated with recurrence in this population.

PMID- 9592631
TI  - Intensity and predictors of treatment received by adolescents with unipolar major
      depression prior to hospital admission.
AB  - We sought to characterize the type and intensity of treatment received in the
      community by 80 adolescents with unipolar major depressive disorder prior to
      hospital admission for this index episode of illness. Structured clinical
      interviews were used to rate the presence and severity of a wide range of
      depressive symptoms and to derive global measures of episode subtype and degree
      of impairment. Multiple sociodemographic and clinical variables were considered
      as predictors of level of antidepressant treatment exposure. Although the
      majority of patients sought help prior to admission, only 58% received
      antidepressant medication, and fewer than half of these treated patients received
      levels of treatment deemed adequate by conventional standards. More aggressive
      levels of pharmacotherapy were received by only a small minority of the sample,
      and overall severity of illness had little effect on intensity of treatment.
      Specific clinical features associated with endogeneity were the most robust
      predictors of more intense antidepressant pharmacotherapy. A disturbingly high
      proportion of adolescents with serious depressive illness receive less than
      optimally aggressive treatment in the community relative to the seriously
      handicapping nature of their illness. The potential implications of these
      observations are considered.

PMID- 9592632
TI  - Treatment of adolescent depression: frequency of services and impact on
      functioning in young adulthood.
AB  - In this report, we (a) present descriptive information about the extent and the
      kinds of treatments being provided to depressed adolescents; (b) identify the
      factors that are related to treatment utilization; and (c) examine whether the
      provision of treatment during adolescence reduced the risk for the occurrence of
      depression during young adulthood (19-24 years). The sample consisted of 1,507
      randomly selected high school students who were diagnostically assessed on two
      occasions with an interval of approximately one year; 627 were assessed a third
      time when they reached the age of 24. The findings may be summarized as follows:
      60.7% of those with major depressive disorder were provided with treatment. The
      modal treatment was outpatient, individual psychotherapy administered by a mental
      health provider. Inpatient treatment and medications were rare. Factors found to
      be related to treatment utilization were the severity of the depression, the
      existence of a comorbid nonaffective disorder, the number of previous episodes of
      depression, history of suicide attempt, academic problems, lack of intact family,
      and female gender. Unexpectedly, those who had received treatment were not less
      likely to relapse into another episode of depression during young adulthood.

PMID- 9592633
TI  - IGF-I and diabetes in adolescence.
AB  - Adolescents with insulin-dependent diabetes mellitus (IDDM) often experience
      difficulties achieving good glycaemic control, and attempts at intensifying
      insulin therapy may increase the risk of hypoglycaemia and weight gain.
      Abnormalities of the GH/IGF-I axis may contribute to these problems. Insulin-like
      growth factor-I (IGF-I) levels and IGF bioactivity are invariably reduced despite
      growth hormone (GH) hypersecretion, and these abnormalities are only partially
      corrected by intensified insulin therapy. The administration of recombinant human
      IGF-I (rhIGF-I) as an adjunct to insulin therapy can restore circulating IGF-I
      levels and thus suppress GH levels and improve insulin sensitivity. Randomised
      placebo-controlled clinical trials of daily subcutaneous rhIGF-I therapy (40-80
      micrograms/kg/day) have demonstrated that significant reductions in HbA1c can be
      achieved without evidence of toxicity or exacerbation of diabetic complications.
      RhIGF-I used in conjunction with insulin may therefore provide an additional
      approach to the management of IDDM during adolescence, although further studies
      are required to determine the ideal dose regimen and confirm beneficial effects
      without adverse effects on microvascular complications in these subjects.

PMID- 9592634
TI  - From physiology to neuroendocrinology: a reappraisal of risk factors of body
      weight gain in humans.
AB  - Obesity results from a chronic imbalance between energy intake and energy
      expenditure. However, the biological mechanism(s) underlying possible alterations
      of energy balance is(are) still poorly defined. Advances in the understanding of
      body weight regulation in humans are represented by the discovery of: a)
      metabolic risk factors of body weight gain (i.e. low resting energy expenditure,
      low level of physical activity, high carbohydrate-to-lipid oxidation rate); b)
      the role of the autonomic nervous system in the control of energy metabolism and
      nutrient partitioning; and c) leptin, a previously unknown hormone produced by
      the adipocyte which seems to be quite involved in the complex neurohormonal
      regulation of energy balance. In view of these discoveries, current models of
      human body weight regulation concord on the existence of crosstalks between
      central nervous system and peripheral tissues. The brain monitors the nutritional
      status of the body (using several peripheral afferent signals including leptin)
      and reacts to nutritional changes by modulating the activity of its neurohormonal
      efferent signaling systems (autonomic nervous systems and endocrine organs). A
      low sympathetic nervous system (SNS) activity and a relative plasma leptin
      deficiency have been shown to predict body weight gain. Furthermore, plasma
      concentration of leptin and activity of the SNS seem to regulate each other. This
      paper reviews the evidence that previously described metabolic risk factors of
      body weight gain (i.e., low resting energy expenditure, low level of physical
      activity, and high carbohydrate-to-lipid oxidation rate) may in fact be the
      phenotypic expression of a dysfunctional leptin-SNS activity body weight
      regulatory loop.

PMID- 9592635
TI  - Aggressive weight reduction treatment in the management of type 2 diabetes.
AB  - Most patients with Type 2 diabetes are significantly overweight, and diet-induced
      weight loss can provide marked improvement in their glycaemic control. As
      conventional therapy combining diet and exercise usually has a poor long-term
      success rate, more aggressive weight reduction programmes have been proposed for
      the treatment of severely obese diabetic patients, including very-low-calorie
      diets, anti-obesity drugs and bariatric surgery. Very-low-calorie diets usually
      have a remarkable short-term effect, and energy restriction and weight reduction
      are positive factors for the glycaemic control of obese diabetic subjects.
      However, the long-term efficacy of these methods remains doubtful since weight
      regain is a common phenomenon. Although anti-obesity (anorectic) drugs may help
      patients to follow a restricted diet and lose weight, their overall efficacy on
      body weight and glycaemia is generally modest, and their long-term safety still
      questionable. Interestingly, serotoninergic anorectic agents have been shown to
      improve both the insulin sensitivity and glycaemic control of obese diabetic
      patients independently of weight loss. Bariatric surgery may be helpful in well
      selected patients. The correction of weight excess after successful gastroplasty
      fully reverses the abnormalities of insulin secretion, clearance and action on
      glucose metabolism present in markedly obese non-diabetic patients, and allows
      interruption or reduction of insulin therapy and antidiabetic oral agents in most
      obese diabetic patients. In conclusion, weight loss is a major goal in treating
      obese patients with Type 2 diabetes, and aggressive weight reduction programmes
      may be used in selected patients refractory to conventional diet and drug
      treatment. However, long-term prospective studies are needed for more precise
      determination of the role of such a strategy in the overall management of obese
      diabetic patients.

PMID- 9592636
TI  - Influence of endogenous and environmental factors on variations of serum
      lipoprotein (a) concentrations in a large population of insulin-treated diabetic
      patients.
AB  - Variations of serum Lp(a) concentrations were studied in a large population of
      insulin-treated diabetic patients in relation to the type of diabetes, insulin
      treatment and long-term complications. Lp(a) concentrations were measured by
      immunonephelometry in 740 diabetic patients [493 insulin-dependent diabetic
      (IDDM) patients and 247 insulin-treated Type 2 diabetic (ITD) patients].
      Concentrations and distributions were compared with those of 128 non-diabetic
      controls. Correlations were investigated with lipidic and glycaemic parameters,
      daily lipid intake, body mass index (BMI), macrovascular and nephropathic
      complications, and insulin therapy. Both groups of insulin-treated patients (IDDM
      and ITD) displayed significantly higher Lp(a) concentrations when compared to
      controls. No relationship was found with macrovascular complications and
      nephropathy, except in IDDM patients in whom Lp(a) was elevated when creatinine
      concentration was above 120 mumol/L. Mean variations of Lp(a) were correlated
      with BMI and triglyceride variations in IDDM patients and only with triglycerides
      in ITD patients. These results suggest a direct and/or indirect (via serum
      triglycerides) potential role of exogenous insulin in the modulation of serum
      Lp(a) concentrations. BMI and lipid daily fat intake could be considered as
      additional modulating factors of Lp(a) serum concentrations in ITD patients.

PMID- 9592637
TI  - Effects of exercise on hypoglycaemic responses in insulin-dependent diabetes
      mellitus.
AB  - This study sought to determine whether moderate exercise influences hypoglycaemic
      responses in insulin-dependent diabetes mellitus (IDDM). Ten patients with IDDM
      and no history of hypoglycaemia unawareness or autonomic neuropathy were
      included. The patients were studied in random order on 4 occasions: twice during
      euglycaemia (once at rest and once on a treadmill) and twice during a gradual
      drop in blood glucose from 5 to 2 mmol/l (once at rest and once on a treadmill).
      Blood samples for hormones and glucose were drawn, and a symptom questionnaire
      was filled out every 5 min. Cognitive tests were performed at the start and end
      of each study. Glucose thresholds for hormones and symptoms are reported as the
      plasma glucose level at which responses were more than two standard deviations
      above basal level and continued to increase. The thresholds for adrenaline and
      noradrenaline release came at a significantly higher blood glucose level during
      exercise than at rest: 2.7 +/- 0.2 vs 2.1 +/- 0.2 mmol/l (p < 0.05) for
      adrenaline and 2.7 +/- 0.2 vs 2.0 +/- 0.1 mmol/l (p < 0.01) for noradrenaline.
      Thresholds for neuroglycopenic symptoms were also at a significantly higher blood
      glucose level during exercise: 2.6 +/- 0.2 vs 2.0 +/- 0.2 mmol/l (p < 0.05).
      During hypoglycaemia, patients showed a non-significant trend towards a lower
      score on cognitive tests during exercise than at rest. It is concluded that
      moderate exercise during a gradual drop in blood glucose does not mask
      hypoglycaemic responses in patients with IDDM.

PMID- 9592638
TI  - Initiating insulin treatment in insulin-requiring type 2 diabetic patients:
      comparative efficiency and cost of outpatient and inpatient management. INNOV
      Study Group.
AB  - The main objective of this randomised study was to compare glycaemic control (as
      determined by HbA1c levels) in two groups of insulin-requiring Type 2 diabetic
      patients three months after initiation of insulin therapy either on an inpatient
      (group A, n = 58) or outpatient (group B, n = 56) basis. Evaluation of the safety
      and cost of both methods was a secondary objective. Although HbA1c level at
      inclusion was slightly but significantly lower in group A than group B (10.17 +/-
      0.19% vs. 10.87 +/- 0.22% respectively, P = 0.019), covariance analysis showed
      equivalent glycaemic control at 3 months in both groups (adjusted means with
      respect to inclusion values: 9.00 +/- 1.14% vs. 9.37 +/- 1.14% respectively;
      equivalence hypothesis: P = 0.01). A low and similar incidence of episodes of
      hypoglycaemia and hyperglycaemia with ketonuria was observed. Clinical tests,
      paramedical care and the cost of hospitalisation itself resulted in a direct cost
      of initiating treatment that was more than four times higher in group A than in
      group B (mean total cost per patient: FF 15,231 and FF 3,296 respectively).
      Insulin-requiring Type 2 diabetic patients can be efficiently and safely started
      on insulin as outpatients, and this approach to initiating insulin therapy is
      cost-effective.

PMID- 9592639
TI  - Insulin dose and cardiovascular risk factors in type 1 diabetic children and
      adolescents.
AB  - Associations between a high daily insulin dose and cardiovascular risk factors,
      including those of the insulin-resistance syndrome, were studied in 479 Type 1
      diabetic children 6 to 18 years of age. Insulin dose increased over the first two
      years after diagnosis of diabetes (p = 0.0001) and was significantly higher in
      girls (p = 0.01). For those children with diabetes duration of more than 2 years,
      the insulin requirement increased up to 13-14 years of age (p < 0.05) and was
      higher in pubertal than pre-pubertal children (p < 0.05). For girls, the
      requirement was higher in puberty than in post-puberty (p < 0.05) and increased
      with diabetes duration (p < 0.05). Triglyceride concentrations were associated
      positively and significantly with the insulin dose of both boys and girls, after
      adjustment for age, pubertal stage, diabetes duration, and metabolic control
      (fructosamine levels). No other consistent associations were found between
      insulin dose and other cardiovascular risk factors: body mass index, central
      adiposity, arterial blood pressures, serum total cholesterol, apoA1, apoB, Lp(a),
      uric acid, or urinary albumin excretion. Parental obesity, hypertension and
      diabetes were not related to the insulin dose of children. The results did not
      differ when the population was limited to the 375 children with diabetes duration
      of more than 2 years. It is concluded that in these Type 1 diabetic children the
      insulin dose for a given level of metabolic control (our surrogate measure of
      insulin resistance) was related to a single cardiovascular risk factor:
      triglyceride concentrations.

PMID- 9592640
TI  - Short-term variations of serum glycated apolipoprotein B.
AB  - Serum glycated apolipoprotein B (apo B-G) levels were determined in 31 non
      insulin-dependent diabetic patients and 13 control subjects by an enzyme-linked
      immunosorbent assay. Apo B-G was increased in diabetic patients compared to non
      diabetic subjects, whether expressed as a serum concentration (57.7 vs 36.1 mg/l)
      or a percentage of total apolipoprotein B (4.42 vs 3.14%). Apo B-G, together with
      other markers (mean daily plasma glucose, serum fructosamines, triglycerides,
      total cholesterol, glycated haemoglobin), was measured before and after 5 days of
      therapeutic adjustment in diabetic patients. In 20 patients with a favourable
      course of glycaemic control, the mean decrease of apo B-G concentration reached
      nearly 16%. In 11 patients with an unfavourable course, the increase of apo B-G
      concentration was about 14%. Therefore, variation of serum apo B-G concentration
      could serve as an additional short-term marker for glycaemic control, although
      possible concomitant variations of serum triglycerides or total apolipoprotein B
      concentrations should also be considered.

PMID- 9592641
TI  - Necrobiosis lipoidica: treatment by hyperbaric oxygen and local corticosteroids.
AB  - Necrobiosis lipoidica (NL) is closely associated with diabetes mellitus. Two
      thirds to three-fourths of patients with NL have diabetes, although NL occurs in
      only 0.3% of diabetic patients. Typical lesions are found on pretibial skin,
      usually in young female diabetic patients whose disease is inadequately
      controlled. The cause of this dermopathy remains unknown. Multiple treatments
      have been described but have not led to consistent results. We report the case of
      a 28-year-old insulin-dependent diabetic woman with a disease duration of 23
      years who spontaneously developed ulcerated NL on pretibial skin. NL
      progressively improved during 113 sessions of hyperbaric oxygen therapy and local
      corticosteroids.

PMID- 9592642
TI  - Concerning the validity of the "FIRI" insulin resistance index.

PMID- 9592643
TI  - [Is it necessary to induce a remission at the onset of type I diabetes?].

PMID- 9592644
TI  - [Cognitive risk from recurrent hypoglycemia in the diabetic].

PMID- 9592645
TI  - [A new strategy for education and management of insulin-dependent diabetics].

PMID- 9592646
TI  - Preparation, premedication and surveillance.

PMID- 9592647
TI  - Reflux disease and Barrett's esophagus.

PMID- 9592648
TI  - Diagnosis of esophagogastric tumors.

PMID- 9592649
TI  - Endoscopic treatment of esophagogastric tumors.

PMID- 9592651
TI  - Treatment of esophagogastric varices: endoscopic, radiological, and
      pharmacological options.

PMID- 9592650
TI  - Ulcers and gastritis.

PMID- 9592652
TI  - Upper gastrointestinal nonvariceal bleeding: a review covering the years 1996-97.

PMID- 9592653
TI  - Percutaneous endoscopic gastrostomy: state of the art, 1998.

PMID- 9592654
TI  - Small-bowel endoscopy.

PMID- 9592655
TI  - Inflammatory bowel disease.

PMID- 9592656
TI  - Colonic tumors.

PMID- 9592657
TI  - Diagnostic endoscopic retrograde cholangiopancreatography.

PMID- 9592658
TI  - Therapeutic biliary endoscopy.

PMID- 9592659
TI  - Current role of endoscopic retrograde cholangiopancreatography in the management
      of benign pancreatic disease.

PMID- 9592660
TI  - Cholangioscopy.

PMID- 9592661
TI  - Diagnostic laparoscopy.

PMID- 9592662
TI  - Endoscopic ultrasonography.

PMID- 9592663
TI  - AIDS and the gastrointestinal tract.

PMID- 9592664
TI  - Complications of endoscopy.

PMID- 9592665
TI  - Minimally invasive surgery.

PMID- 9592666
TI  - Clinical experience with vestibular schwannomas: epidemiology, symptomatology,
      diagnosis, and surgical results.
AB  - The Danish model for vestibular schwannoma (VS) surgery has been influenced by
      some historical otological events, taking its origin in the fact that the first
      attempt to remove CPA tumors was performed by an otologist in 1916. In
      approximately 50 years VS surgery was performed by neurosurgeons in a
      decentralized model. Highly specialized neuro- and otosurgeons have been included
      in our team since the early beginning of the centralized Danish model of VS
      surgery in 1976. Our surgical practice has always been performed on the basis of
      known and proven knowledge, but we spared no effort to search for innovative
      procedures. The present paper reflects the experience we have gained in two
      decades of VS surgery. Our studies on the incidence, symptomatology, diagnosis,
      expectancy and surgical results are presented.

PMID- 9592667
TI  - Acoustic reflex threshold and loudness in patients with unilateral hearing
      losses.
AB  - The relationship between the acoustic reflex threshold (ART) and loudness was
      examined in patients with unilateral hearing losses and subjects with simulated
      hearing losses using a masking method. Significant differences in the ART between
      the two ears of patients with unilateral hearing losses were correlated with
      differences in loudness at the level of the ART with differences in loudness
      determined by the alternate binaural loudness balance test. A similar
      relationship of ART and the sensation of loudness was also observed in ears with
      simulated hearing losses. The results obtained in the present study suggest a
      positive relationship between the ART and loudness, and provide some support for
      the assumption that a common neuronal information pathway plays an important role
      both in producing the loudness and eliciting the acoustic reflex.

PMID- 9592668
TI  - Laryngotracheal stenosis in children.
AB  - The diagnosis of laryngotracheal stenosis should be suspected in children with
      stridor, feeding difficulties, or atypical croup. Only half of the children with
      congenital laryngotracheal stenosis require tracheotomy, and many of these
      children can be decannulated following uncomplicated surgical therapy. In
      contrast, tracheotomy-dependent patients with acquired laryngotracheal stenosis
      require more extensive surgical intervention, which should be carried out as
      early as possible to provide the best opportunity for developing normal oral
      communication.

PMID- 9592669
TI  - Solitary fibrous tumor of the parotid gland extending to the parapharyngeal
      space.
AB  - Solitary fibrous tumors (SFT) arise in the pleura and less commonly in
      extrapleural sites. Head and neck regions have included the nose and paranasal
      sinuses, soft palate, epiglottis, thyroid, parotid and submandibular glands, as
      well as the infratemporal fossa and parapharyngeal space. We report a case of SFT
      arising from the parotid gland and extending to the parapharyngeal space. To our
      knowledge, this is the fourth case of SFT originating from the parotid gland and
      is the largest of its kind among the extrapleural lesions described. The
      characteristics revealed by computed tomography and magnetic resonance imaging
      are presented.

PMID- 9592670
TI  - The alteration of craniofacial pain in patients with chronic rhinosinusitis
      before and after nasal and sinus surgery.

PMID- 9592671
TI  - Pharyngoesophageal reconstruction with the tubed radial forearm free flap.

PMID- 9592672
TI  - Cochlear implantation after subtotal petrosectomies.
AB  - Among cochlear implant candidates there are patients who have abnormal middle
      and/or inner-ear conditions that make them unsuitable for implantation. Insertion
      of a foreign body may also be contraindicated in the setting of an existing or
      potential intracranial communication, or when the ear is prone to infection. Five
      patients presented with such unfavorable conditions. These included a Mondini
      dysplasia with persistent cerebrospinal fluid leak, an atretic mastoid with
      meningocele, chronic otitis media, a transverse petrous bone fracture, and a
      temporal bone adenoma. All patients underwent subtotal petrosectomies and
      cochlear implantations. In four cases implantation was performed concomitantly
      with subtotal petrosectomy, while the remaining case required a two-stage
      procedure. No complications occurred. The technique is described in detail, and
      the cases and the indications for surgery are discussed. By obliterating and
      isolating the tympanomastoid cleft from the outer environment and utilizing the
      technique of subtotal petrosectomy, a broader spectrum of patients can now be
      implanted safely.

PMID- 9592673
TI  - Cochlear implantation as a successful rehabilitation for radiation-induced
      deafness.
AB  - Radiotherapy of the head and neck can be associated with conductive and/or
      sensori-neural hearing loss. We report the case of a 67-year-old man who
      developed complete bilateral deafness caused by labyrinthitis and radiation
      induced neuritis of the acoustic nerve after postoperative radiotherapy of a
      nasopharyngeal carcinoma. Two years postoperatively extensive clinical workup
      including computed tomography and magnetic resonance imaging showed no recurrence
      or secondary brain tumors. To facilitate sound perception a Combi 40 cochlear
      implant was implanted. Because of fibrosis the insertion depth of the stimulating
      electrode into the scala tympani was limited and therefore a "short electrode
      version" was used. Six months after implantation the patient had achieved an
      excellent environmental sound recognition and moderate speech intelligibility.
      Present experiences has shown that although radiotherapy can cause damage to the
      labyrinth and acoustic nerves and central hearing pathways, there may still be
      surviving auditory nerve fibers that can be stimulated successfully by a cochlear
      implant.

PMID- 9592674
TI  - Expression profile of vascular cell adhesion molecule-1 (CD106) in the middle ear
      using radiolabeled monoclonal antibody.
AB  - Adhesive interactions between leukocytes and endothelium are required for
      subsequent leukocyte extravasation toward inflammatory sites. Understanding the
      possible kinetic expression of vascular cell adhesion molecule-1 (VCAM-1) in the
      middle ear cavity during an inflammatory cascade in vivo may be important for
      clarifying local immunological responses in otitis media. Two inflammatory models
      were produced in the rat and involved acute middle ear mucosal and cutaneous
      inflammation induced after inoculation or intradermal injection of
      lipopolysaccharide (LPS). After intravenous injection of both 125I-labeled anti
      VCAM-1 and 131I-labeled control monoclonal antibody (mAb), the kinetic expression
      of VCAM-1 in the middle ear and skin was assessed by local radionuclide uptake.
      The biodistribution of an 125I-labeled anti-VCAM-1 mAb as a potential detector of
      focal inflammation was examined in normal rats. Both inflammatory lesions were
      characterized by early and sustained (up to 24 h) expression of VCAM-1, with
      maximal expression at 4 h after LPS stimulation. The kinetics of VCAM-1
      expression was similar among the middle ear mucosa or skin specimens studied and
      different stimulation methods. A similar biodistribution and clearance of
      radioactivity between 125I-labeled anti-VCAM-1 mAb and 131I- or 99mTc-labeled
      control mAb were observed. The present result suggest that functional VCAM-1
      induced by LPS is expressed in both middle ear tissue and skin lesions and may
      play a role in the initial stage of inflammatory response produced. Although VCAM
      1 upregulation is a very early event in the inflammatory cascade, 125I-labeled
      anti-VCAM-1 mAb may be useful for the early detection of focal inflammation in
      the middle ear.

PMID- 9592675
TI  - Lipopolysaccharide-induced expression of nitric oxide synthase II in the guinea
      pig vestibular end organ.
AB  - The purpose of the investigation was to ascertain whether inoculation of
      bacterial lipopolysaccharide (LPS) into the vestibular organ of the guinea pig
      might induce formation of nitric oxide synthase (NOS) II. Forty-eight hours after
      the animals were injected with 1 mg transtympanic LPS, varying degrees of
      impaired caloric responses were observed with similar degeneration of vestibular
      hair cells. These effects could be blocked with N-nitro-L-arginine methylester, a
      competitive inhibitor of NOS. Findings suggested that NOS II, which was not
      normally detectable in the guinea pig vestibular organ but was present following
      inoculation of LPS, produced the nitric oxide as the toxic factor causing cell
      damage. If true, LPS may represent a reproducible method for studying the
      vestibular pathogenesis of inner ear disease.

PMID- 9592676
TI  - Clinical-histopathological correlations of pitfalls in middle ear surgery.
AB  - Significant anatomical variations within the middle ear are described as well as
      atypical histopathological findings in 13 selected human temporal bones. Bones
      studied included such vascular and bony abnormalities as carotid artery canal
      dehiscence, a high jugular bulb, persistent stapedial artery and facial nerve
      canal dehiscences. Bones also included obliterative otosclerosis, malleus head
      fixation and a variety of chronic inflammatory changes and/or sequelae. Those
      features considered to render cases prone to complications are detailed.

PMID- 9592677
TI  - The anti-inflammatory effect of fusafungine during experimentally induced
      rhinosinusitis in the rabbit.
AB  - The short-term effects of local intranasal administration of fusafungine were
      studied for its anti-inflammatory and antimicrobial properties against
      experimentally induced bacterial rhinosinusitis. The maxillary sinuses of 20
      rabbits were infected with encapsulated Streptococcus pneumoniae after mechanical
      occlusion of each animal's anatomic ostium. Either fusafungine solution or
      placebo was administered as a nasal spray through the nostrils twice daily for 10
      days. Histopathological grading of inflammation, biochemical assay of
      inflammatory mediators, and the number of bacterial species isolated from the
      nasal cavities all showed significant recovery from inflammation after
      fusafungine treatment. The beneficial effects of fusafungine on inflamed sinus
      mucosa may possibly also be attributable to an initial alleviation of
      inflammation in the nasal cavity, which permitted entry of the drug to the sinus
      cavity through a partially reopened ostium. A reciprocal relationship between
      nasal and sinus reactivity involving generalization of inflammation and recovery
      was also thought to be of importance. The present findings indicate that local
      applications of fusafungine may effectively improve clinical conditions producing
      rhinitis and sinusitis.

PMID- 9592678
TI  - A comparative study of the ciliary area of the maxillary sinus mucosa and
      computed tomographic images.
AB  - The ciliary area of the maxillary sinus mucosa and coronal sinus computed
      tomographic (CT) scans were studied in 36 maxillary sinuses of 28 patients with
      chronic sinusitis. Tissue specimens allowed ciliary surfaces to be observed under
      scanning electron microscopy, allowing surfaces to be expressed in terms of
      ciliary area (CA) as the percentage of mucosal surface occupied by cilia. The
      opacity produced by mucosal swelling and secretion in the maxillary sinus on CT
      was assessed by two methods: Min's and modified van der Veken's methods. Both
      techniques indicated an inverse correlation between opacity of the maxillary
      sinus and CA. Our findings suggest that the opacity of maxillary sinus on CT
      could be a significant parameter for predicting the surface conditions of
      ciliated maxillary mucosa prior to sinus surgery.

PMID- 9592679
TI  - Bazex syndrome (acrokeratosis paraneoplastica).
AB  - Acrokeratosis paraneoplastica (Bazex syndrome) is a rare but distinctive
      dermatosis associated with carcinomas of the upper aerodigestive tract with
      possible cervical lymph node metastases. The cutaneous lesions occurring in the
      syndrome are non-metastatic skin involvement that parallels (as cutaneous marker)
      the evolution of the malignancy. Since only a few case reports have been
      published in the otolaryngologic literature, we present our experience and review
      some of the findings previously reported.

PMID- 9592680
TI  - Magnetic cell separation for purification of human oral keratinocytes: an
      effective method for functional studies without prior cell subcultivation.
AB  - In studying human oral keratinocytes, it would be very helpful to obtain a pure
      population of cells without prior in vitro expansion. An immunomagnetic
      separation technique, or magnetic cell separation (MACS), was modified for
      efficient purification of human oral keratinocytes. Subsequent to two-step
      enzymatic digestion, the cell suspension was labelled with a mouse anti-CD45 (pan
      leukocyte) monoclonal antibody (MoAb) to stain mononuclear cells. In a second
      step a rat anti-mouse antibody conjugated with colloidal superparamagnetic
      particles was used. Labelled cells were retained in the magnetic field of a
      permanent magnet on columns containing a ferromagnetic matrix. The unlabelled,
      unretained cells were further examined by flow cytometry analysis, enzyme-linked
      immunosorbent assay and polymerase chain reaction. After the MACS procedure,
      unretained cells showed a strong positivity for the lu-5 MoAb (as a marker for
      pan-cytokeratin) and were negative for anti-vimentin (to mark mesenchymal cells),
      for anti-CD45 MoAb and for melanocyte-detecting antibodies, thus representing
      pure keratinocytes (> 98%). Purified keratinocytes maintained full viability (>
      91%) and functional capacities. [3H]thymidine uptake and epidermal growth factor
      (EGF) receptor expression were unaltered when compared with the non-separated
      cell population. Furthermore, interleukin-1 alpha was detected at the protein and
      RNA levels in keratinocytes immediately after MACS enrichment. Our findings show
      that MACS appears to be a useful tool for purification of oral keratinocytes and
      allows for further functional studies without prior subcultivation of cells.

PMID- 9592681
TI  - Possible prognostic value of histopathologic parameters in patients with
      carcinoma of the oral tongue.
AB  - The current TNM staging system is helpful but still not enough to accurately
      determine prognosis of the patients with squamous cell carcinomas of the oral
      tongue. Histopathologic variables, however, may be more helpful for predicting
      nodal metastasis and locoregional recurrences. In this respect, histopathologic
      examinations were done retrospectively of tumor specimens from 60 patients with
      squamous cell carcinomas of the oral tongue. Besides T-stage and nodal
      involvement, histopathologic parameters of tumor thickness, perineural invasion,
      lymphovascular space invasion, the extent of lymphocyte infiltration and the
      invasion pattern statistically correlated with locoregional recurrences. For
      nodal metastasis, tumor thickness of 10 mm or more and the type of invasion
      pattern were statistically significant. These results revealed that the variables
      described should be used for managing oral tongue cancers.

PMID- 9592682
TI  - Relationship between hypertension and renal function and its therapeutic
      implications in the elderly.
AB  - The kidney is an important target of hypertension-induced organ damage. Recent
      long-term observation studies have documented that in individuals, without
      primary chronic renal disease, a very significant relationship exists between
      hypertension and impaired renal function, elderly hypertensives having a
      particularly worse prognosis. The hallmark of hypertensive renal injury is
      thought to be a progressive increase in intrarenal vascular resistance. The
      alterations in renal hemodynamics are accentuated in elderly patients with
      essential hypertension, pointing to a greater vulnerability of the senescent
      kidney to superimposed injury such as high blood pressure. Treatment of elevated
      blood pressure in the elderly therefore not only reduces cardiovascular morbidity
      and mortality, but also reduces the incidence of renal failure as a consequence
      of hypertension-induced damage.

PMID- 9592683
TI  - Influence of aging on cortical and trabecular bone response to estradiol
      treatment in ovariectomized rats.
AB  - Three groups (n = 15/group) of 6-, 12- and 30-month-old (mature, old and
      senescent animals, respectively) female Wistar rats on a diet (6 g/100 g BW/ day)
      containing 0.8% calcium and 0.8% inorganic phosphorus were studied. Within each
      group, 10 rats were ovariectomized surgically and 5 injected s.c. with 17 beta
      estradiol (E rats, 10 micrograms/kg BW/48 h) and 5 with solvent alone (OVX rats)
      from day 2 until day 60 after ovariectomy. Five other rats were sham-operated (SH
      rats) and received solvent only. All rats were killed by exsanguination 60 days
      after ovariectomy. Neither ovariectomy nor estradiol treatment had a significant
      effect upon tibial mechanical properties in 6-, 12- and 30-month-old animals.
      Bone mineral density (BMD) and bone mineral content (BMC) of the distal femur and
      BMC of the whole femur were decreased by ovariectomy in 6- and 12-month-old rats,
      but were not different in the SH and E groups. In senescent animals, in which the
      lowest BMD and BMC were measured, estradiol treatment was more effective in
      increasing these parameters than in adult and old rats. Image analysis of the
      distal femoral diaphysis showed that estradiol treatment prevented trabecular
      bone loss induced by senescence and/or ovariectomy. In each group, urinary
      deoxypyridinoline excretion and plasma osteocalcin concentration were higher in
      the OVX animals than in the controls, consistent with increased bone turnover in
      the estrogen-deficient state. Both biochemical turnover markers were reduced in
      the estrogen-treated groups. These results indicate that 17 beta-estradiol is
      particularly effective at preventing high-turnover-induced osteopenia in 30-month
      old animals.

PMID- 9592684
TI  - Enlarging effects of estradiol on the nuclear volume of neurons in the
      hypothalamus during aging.
AB  - Neuronal nuclear volumes (NNVs) were measured in the medial preoptic nucleus
      (MPN), anterior hypothalamic area (AHA) and arcuate nucleus (ARN) of young adult,
      middle-aged, and old rats of both sexes. The NNVs in the darkly stained sexual
      dimorphic nucleus of the preoptic area (SDN-POA) and the lighter staining
      surrounding area (non-SDN-POA) within the MPN were measured separately. Intact
      young and middle-aged female rats had larger NNVs than those of the males in SDN
      POA, non-SDN-POA and AHA but not in ARN. During aging, only intact old female
      rats manifested significant NNV shrinkage in all the measured areas. Long-term
      treatment with estradiol benzoate (EB) caused a significant enlargement of the
      NNVs in non-SDN-POA and ARN of middle-aged and old male rats as well as the NNVs
      in SDN-POA, non-SDN-POA and ARN of old female rats. The enlarging effect of EB on
      NNVs in both SDN-POA and non-SDN-POA of female rats could be prevented by
      ovariectomy. Furthermore, NNVs in SDN-POA and non-SDN-POA of ovariectomized
      female rats were even smaller than those of the age-matched intact female rats.
      These results indicate that: (1) the NNVs of MPN and ARN in male and female rats
      were enlarged after long-term exposure of physiological dose of estradiol; (2)
      the enlarging effects of EB on NNV in MPN can explain why the NNV of intact
      female rats is larger than that of males, and (3) during aging, the sex-specific
      shrinkage of NNVs in MPN, AHA and ARN of female rats may be due to an intrinsic
      aging process rather than long-term effects of EB.

PMID- 9592685
TI  - Insulin stimulates collagen synthesis in vascular smooth muscle cells from
      elderly patients.
AB  - The process of aging results in an increase in collagen in arterial walls, but
      the blood levels of insulin-like growth factor 1 (IGF-1) decrease remarkably as
      adults age. There is an almost simultaneous increase in insulin secretion,
      particularly in obese individuals. It is not known if, under these hormonal
      conditions, the enrichment of collagen in the arterial wall is due to insulin. We
      studied the effect of insulin on the production of collagen in vascular smooth
      muscle cells (VSMC) from elderly persons with high levels of insulin secretion
      after blocking the insulin receptors with a monoclonal antibody. Results were
      compared to those without insulin receptor blockage and to those with IGF-1.
      Despite the inhibition of 14C-glucose uptake, insulin clearly stimulated the
      release of procollagen III, and increased the collagen synthesis. The
      hydroxyproline labelling rate from 3H-proline increased to more than twice the
      control values. IGF-1 is a more potent effector than insulin, but the effect of
      insulin on the rate of collagen production became similar to IGF-1 when the
      specific receptors were blocked. The results indicate that under special
      conditions that occur with aging, insulin interacts with nonspecific receptors in
      VSMC, especially IGF-1, stimulating these cells to produce collagen.

PMID- 9592686
TI  - Phenotypic changes in vascular smooth muscle cells during aging: insulin effect
      on migration.
AB  - We examined the mechanisms by which insulin may be atherogenic during aging. We
      postulated that an increase in insulin secretion during aging produces growth
      factor effects on vascular smooth muscle cells (VSMCs), promoting these cells to
      synthesize collagen and to migrate. We have previously demonstrated that insulin
      stimulates collagen synthesis and release in senescent VSMCs that were obtained
      from a human organism with high levels of insulin secretion. Using the same
      experimental model, we now study the effects of insulin on VSMC migration. We
      demonstrate that insulin has a chemoattractant effect on VSMCs which occurs
      through insulin binding to its own specific receptors as opposed to its effect on
      collagen production. Blocking the insulin receptor significantly eliminates the
      insulin effect on cell migration. At the same molarity, the chemotactic effect of
      insulin is less pronounced than that of insulin-like growth factor-1. In spite of
      different mechanisms, there is a remarkable correlation between the insulin
      effects on collagen secretion and cell migration (r2 = 97%, p < 0.0005). Our
      results indicate that distinct but closely related mechanisms may exist by which
      insulin becomes atherogenic. Our results also suggest the importance of normal
      aging processes in the development of atherosclerosis.

PMID- 9592687
TI  - The long-term clinical outcome of elderly patients with Helicobacter pylori
      associated peptic ulcer disease.
AB  - The objective of this study was to evaluate the long-term efficacy of
      Helicobacter pylori (HP) eradication treatment in elderly patients with HP
      associated peptic ulcer. A total of 56 subjects, 25 affected with gastric ulcer
      (GU, 9 males, 16 females, mean age 77.8 years, range 67-93) and 31 with duodenal
      ulcer (DU, 19 males, 12 females, mean age 76.5 years, range 65-87) were confirmed
      to be HP-positive by gastric histology and the rapid urease test. All patients
      were then consecutively treated with omeprazole for 4 weeks plus one or two
      antibiotics for 1 week as anti-HP treatment. Clinical checkups were then
      performed every 3 months for 1 year for the evaluation of symptoms and clinical
      recurrences. Endoscopy with gastric biopsies was repeated after 1, 3 and 12
      months for the evaluation of ulcer healing, HP infection and chronic gastritis
      activity. Statistical analysis was performed by means of the Student t test for
      unpaired data, the Fisher exact test (two-tailed), and the McNemar chi 2 test.
      After 4 weeks of treatment, endoscopy confirmed healing of the ulcer in all
      patients, regardless of the treatment used to cure HP infection. Two months after
      the end of therapy, a total of 44 patients were HP-negative and 12 patients were
      still HP-positive. During the 1-year follow-up period 1/44 (2.2%) of the HP
      eradicated patients and 5/12 (41.6%) of the still HP-positive patients suffered
      relapses (p = 0.001): the difference between the two groups remained
      statistically significant when patients were divided into the subgroups, GU (p =
      0.01) and DU (p = 0.04). Two months after the end of therapy, there was still a
      significant reduction of symptoms both in HP-eradicated (p < 0.0000) and in HP
      positive (p = 0.002) patients. After 1 year, however, there was a significantly
      decreased symptomatology only in HP-eradicated subjects (p < 0.0000) and not in
      patients still HP-positive. After both 2 months and 1 year of follow-up, chronic
      gastritis activity demonstrated a significant improvement only in HP-eradicated
      patients (p = 0.0000). In conclusion, the eradication of HP infection
      significantly improved the long-term clinical outcome of peptic ulcer disease in
      the elderly, reducing the recurrences of GU and DU, the patient's symptomatology
      and the histological signs of chronic gastritis activity. The cure of HP
      infection is, therefore, strongly recommended in elderly patients with HP
      associated peptic ulcer disease.

PMID- 9592688
TI  - Ageing and rheological properties of facial skin in women.
AB  - Ageing affects the mechanical properties of skin. Studies using objective
      measurements on facial skin have been rare and yielded contradictory information.
      In the present study, the age-related changes occurring in the mechanical
      properties of facial skin were reviewed using a computerized suction method. A
      total of 200 healthy women, aged from 17 to 68 years, were enrolled. Data show a
      significant increase in skin extensibility and a significant decline in
      elasticity with ageing. These changes become obvious in women approaching 40
      years.

PMID- 9592689
TI  - Prevalence study of thyroid dysfunction in the elderly of Taiwan.
AB  - The present study was aimed at investigating the prevalence of thyroid
      dysfunction in the elderly, aged 65 years or older, in a community of southern
      Taiwan. By using the records of the local household registry, a sampling frame
      for the elderly population was constructed, and a sample of 1,400 subjects was
      drawn by simple random sampling. After the exclusion of nonresponse subjects, 917
      subjects aged between 65 and 88 years (mean 71.9) were included in our survey.
      The serum thyrotropin levels of these participants were measured by monoclonal
      antibodies TSH immunoradiometric assays. A normal range, 0.45-4.65 microU/ml, was
      determined from the middle 95% of the TSH distribution of 140 'disease-free'
      subjects. By reference to the normal range, 23 (2.51%) participants had high (>
      4.65 microU/ml), and 41 (4.47%) had low (< 0.46 microU/ml) TSH levels. The
      overall prevalence of thyroid dysfunction in the sample was 6.98%. Of the 23
      participants with high TSH levels, 8 (34.8%) had low free T4 values (< 1.21
      ng/dl), so-called overt hypothyroidism, and of the 41 participants with low TSH
      levels, only 1 (2.4%) had high T3 values, so-called T3 thyrotoxicosis.
      Antithyroid antibodies were found in 56.5% of those with high TSH levels but only
      12.2% of those with low TSH levels (odds ratio = 8.53, 95% confidence limits =
      2.55-28.50, p < 0.001). This result indicates that autoimmune disease is still
      the major cause of hypothyroidism in aged people. However, the prevalence of
      subclinical hyperthyroidism is higher than that of subclinical hypothyroidism and
      it might relate to nonautoimmune factors.

PMID- 9592690
TI  - Clinical associations of lymphopenia in elderly persons admitted to acute medical
      and psychiatric wards.
AB  - Lymphopenia is a common finding in old people admitted to medical and psychiatric
      wards. We describe a pilot study of the clinical associations, and prognostic
      significance of lymphopenia in elderly persons admitted to acute medical and
      psychiatric wards. Consecutive patients admitted to acute medical and psychiatric
      wards were prospectively selected according to initial peripheral lymphocyte
      count (PLC) into lymphopenic (PLC < 1.0 X 10(9)/litre, n = 41), and non
      lymphopenic (PLC > 1.5 x 10(9)/litre, n = 23). Results of routine haematological
      and biochemical investigations were recorded, as well as drug history and medical
      diagnoses. Anthropometric measurements, assessment of functional ability (Barthel
      ADL Index), and cognitive function (Mini-Mental State Examination) were then
      performed by investigators blind to lymphocyte status. Patients were contacted
      between 3 and 6 months following recruitment into the study. Lymphopenia was
      associated with functional ability as measured by a lower Barthel score (p =
      0.004), and cognitive impairment as measured by the Mini-Mental State Examination
      (p = 0.02). No association was found with medical diagnostic groupings, drugs
      known to cause lymphopenia, nutritional status, or survival. Lymphopenia may be a
      significant marker of vulnerability, and a larger study is required to elucidate
      the veracity and mechanisms of lymphopenia-associated debility.

PMID- 9592692
TI  - How older people watch television. Telemetric data on the TV use in Germany in
      1996.
AB  - This study has been prompted by the relatively small body of knowledge on the
      media use of the elderly. The aim of this study was to show how people 50 years
      and older use the medium television in Germany. Therefore, the 1996 television
      usership data collected in a representative 'peoplemeter' panel of about 4,800
      German television households have been surveyed, processed and analyzed using
      standard audience research software. In 1996, Germans 50 years and above watched
      on average 233 min television per day. The older a person, the longer he or she
      watches television. Individuals 65 years and older watch television for 253 min
      per day. This subgroup appears to comprise the most intensive users of the
      medium. Men 65 years and above may be depicted as the heaviest weekend TV
      watchers, older women as the medium's closest followers from Monday to Friday.
      Television program broadcast late in the afternoon and early in the evening have
      by far the best chances to be chosen by seniors. The affinity of the elderly for
      the medium can be explained by its potential for offering entertainment,
      information, and companionship, being a substitute for primary interpersonal
      communication, a tool for structuring time patterns and keeping up the rhythms of
      long-established everyday rituals. On the one hand, television can be a
      'lifeline' and a 'window to the outside world' for people with little opportunity
      for direct, unmediated social contact, thus possibly raising their satisfaction
      of life. On the other hand, prolonged TV use may be seen as an indicator for the
      degree of loneliness and neglect of the elderly.

PMID- 9592691
TI  - Tetanus in the elderly: is it different from that in younger age groups?
AB  - Our aims were to itemize the clinical features and the outcome of tetanus in the
      elderly, as well as any age and sex differences in its acquisition. Therefore, we
      compared the demographic and clinical data of 12 elderly (group 1) cases of
      tetanus with 69 middle-aged patients (group 2) and 12 children (group 3)
      suffering from the same disease. There was no significant difference between the
      site of entry and incubation period or in the clinical and paraclinical findings
      among the three groups of patients. Acute respiratory failure was found more
      commonly in group 1 than in groups 2 and 3 (p = 0.0167 and p = 0.0006,
      respectively). It was also more common in group 2 than in group 3 (p = 0.0140). A
      mild form of tetanus was more often detected in children than in middle-aged and
      elderly cases (p = 0.0213 and p = 0.0013, respectively). Severe tetanus was seen
      more often in group 1 than in groups 2 and 3 (p = 0.0167 and p = 0.0006,
      respectively). Despite this, the mortality rate was not statistically different
      among the three groups of patients. Females were affected much less frequently
      than males with a female:male ratio of 1:3 in all three age groups. Our results
      suggest that elderly patients are at higher risk of acquiring a more severe form
      of tetanus and the subsequent development of acute respiratory failure. In
      addition, the disease is more common in males of all age groups, and age and sex
      have no apparent effect on the outcome of patients with tetanus.

PMID- 9592693
TI  - [Epidermolysis bullosa hereditaria dystrophica mutilans Hallopeau-Siemens--a
      complex problem].
AB  - Epidermolysis bullosa hereditaria dystrophica mutilans Hallopeau-Siemens is an
      autosomal recessive, chronically mutilating disease. Causal therapy is not known.
      In a five-year-old boy suffering from this disease and having the right hand
      completely clumped to a fist, syndactyly and contraction release was performed.
      The wounds healed under the care of the silicone-coated polyamide net dressing
      Mepitel. Under intensive postoperative physio- and ergotherapeutic care, a major
      part of his previous hand function could be restored. Complete epithelialization
      occurred within four weeks. Twelve months after the procedure, the area of the
      previous lesions was marked by an unexpected mechanical stability. It was very
      impressive to see the improvement in his psychological well-being and his sense
      of self-esteem during this period of partial recovery of his hand function.

PMID- 9592694
TI  - [The posterior interosseous flap--review and personal experience].
AB  - The posterior interosseous flap was first introduced by Zancolli and Angrigiani
      (1985) and short time later by Penteado and Masquelet (1986). The flap is used
      for soft tissue reconstruction in the hand but has not gained wide acceptance due
      to tedious pedicle dissection and venous problems. In 1993, Angrigiani et al.
      published a simplified modification in the elevation of the flap. They included a
      constant fasciocutaneous perforating vessel in the flap to enhance the viability.
      We applied the modified elevation technique in twelve patients. Our experience,
      indications, and complications will be discussed. In contrast to Angrigiani's
      statement, our flaps still show a temporary mild to moderate venous congestion
      similar to the flaps raised in the original technique.

PMID- 9592695
TI  - [Use of the internal mammary artery in reconstructive microsurgery in the
      thoracic region: anatomical-radiologic study].
AB  - In this study, the topographic anatomy and the diameter of the internal mammary
      (thoracic) vessels was investigated in regard to their potential as a recipient
      vessel in reconstructive microsurgery in the ventral thoracic region.
      Particularly for reconstruction of large thoracic wall defects as well as for
      female breast reconstruction with free tissue transplantation, these vessels seem
      to be suitable due to their location. We performed an anatomical study on 86
      cadavers and a radiological investigation on 50 female patients and volunteers.
      We found a mean diameter on 50 female patients and volunteers. We found a mean
      diameter of 1.8 mm of the artery and 2.1 mm of the commitant vein at the level of
      the fourth rib, one to two centimeters parasternally. We conclude that the
      internal mammary vessels can serve as recipient vessels in reconstructive
      microsurgery in the ventral thoracic region at the level of the fourth rib or
      cranially. Hypothetically, free muscle flaps for the treatment of sternal
      osteitis, free fasciocutaneous flaps to replace presternal burn scars or
      appropriate flaps to fill up a funnel chest cavity subcutaneously may be
      anastomosed to the internal mammary vessels.

PMID- 9592696
TI  - [External stabilization of the metacarpal bones II to V. Anatomic-clinical
      study].
AB  - The four ulnar metacarpal bones are connected to each other at their proximal and
      distal ends by strong ligaments. The second and fifth metacarpal bones are the
      frame of the metacarpus. Surgically, this is of great importance. A fracture of
      these two bones often requires stabilization, whereas a fracture of the third and
      fourth metacarpal bones with intact ligaments seldom requires surgery except in
      cases of severe fragment dislocation. Using external fixation for these purposes
      it seems to be of utmost interest to define secure pintracks through the soft
      tissue. In an anatomical study using formalin fixed specimen it clearly could be
      demonstrated that the second and fifth metacarpal bones are best suited for
      external fixation. The second metacarpal bone should always be fixed from the
      radial side because the fixator pins can be inserted within a wide range of
      angles without the risk of violating the extensor tendons. Variations of tendons
      and ligaments are seldom located on the radial side of the second metacarpal bone
      and therefore, finger movement is unhindered after pin application. A similar
      consideration is true for the fifth metacarpal bone which should be fixed from
      the ulnar side. With respect to the extensor tendon which covers the entire
      dorsal surface of the fifth metacarpal bone, the angle of the pins should be 40
      to 90 degrees from the dorsal side. For the third metacarpal bone, fixation from
      the radial side is preferable taking topographical and biomechanical
      considerations into account. The radial corridor to the fourth metacarpal bone is
      smaller than the ulnar corridor, but there is much less morphological variability
      of the extensor tendons than on the ulnar side where strong fibres often cross
      the fourth intermetacarpal space. Because in the proximal fourth of the
      metacarpal bones the tendons are located very close to each other, a small skin
      incision and preparation to the bone surface is advisable to exclude violation of
      the tendons when inserting fixator screws into the third and fourth metacarpal
      bones. Using formalin-alcohol fixed cadaver specimens for the research gives an
      idea of the anatomical situation in the dorsal metacarpus but cannot answer the
      question whether the tendons in the lax subcutaneous tissue of the living will
      automatically slip aside when the fixator pin approaches. This should be item to
      subsequent studies in fresh frozen specimens and follow-up studies in a larger
      amount of patients treated with external fixation.

PMID- 9592697
TI  - [The supinator syndrome].
AB  - BACKGROUND: The posterior interosseous nerve syndrome is a rare compression
      neuropathy of the upper limb, which must be differentiated from tennis elbow. The
      aim of our study is to show etiology, symptoms, and diagnostic methods, and to
      illustrate the common operative techniques. PATIENTS AND METHODS: We examined
      retrospectively all patients of the Department for Hand Surgery, Plastic and
      Microsurgery of the Berufsgenossenschaftlichen Unfallkrankenhaus Hamburg, who
      underwent operative treatment because of posterior interosseous nerve syndrome
      between 1984 and 1992. Mobility of the elbow joint, postoperative complaints and
      patient's satisfaction were analysed. RESULTS: 23% of patients suffered a
      reduction of motion of the elbow joint, 87% had less pain, and 83% were satisfied
      with the result of treatment. CONCLUSIONS: The value of preoperative
      neurophysiological examination for diagnosis of posterior interosseous nerve
      syndrome is not clear. Clinical examination will allow to differentiate between
      posterior interosseous nerve syndrome and tennis elbow. To prevent incomplete
      decompression of the deep radial nerve, multiple locations of compression must be
      considered.

PMID- 9592698
TI  - [Results of restoration of continuity in peripheral nerves in childhood and
      adolescence].
AB  - According to several studies, results after reconstructive procedures in children
      are generally superior compared to those in adults. In the present retrospective
      study, 20 patients after reconstruction of one or more major nerves in the upper
      limb (median, ulnar, and radial nerves) were examined. At the time of operation,
      the patients' age was 8.9 years on the average, the follow-up time ranged between
      29 and 173 months. In six cases the nerve lesion had been treated by direct nerve
      coaptation, in 14 patients a primary or secondary nerve grafting procedure had
      been applied. The results were classified according to Millesi's examination
      system, which takes several factors such as mobility, sensibility, skill, and
      force of the hand into account. Besides two patients, one after reconstruction of
      the median and ulnar nerves by grafts with significant destruction of the muscles
      in the lower arm, and the second one after primary coaptation of the median and
      ulnar nerves in the elbow region, all patients showed a hand function of more
      than 70% according to Millesi's scoring system. In patients older than ten years
      at the time of the reconstructive procedure, results were slightly worse than in
      younger individuals. Children up to ten years of age were nearly always able to
      move their hand and fingers normally. The results after nerve grafting were
      sometimes even superior to those after primary neurorrhaphy. Therefore, the
      present study supports the findings of previous authors describing the excellent
      regenerative potential of the growing peripheral nervous system. Furthermore,
      Millesi's scoring system better revealed some subtle differences in hand function
      when compared to other classifications.

PMID- 9592699
TI  - [Nerve coaptation using CO2 milliwatt laser].
AB  - The technique of laser tissue welding with a low-output CO2 laser has become
      popular due to the minimal amount of nerve tissue damage caused. The purpose of
      this study was to ascertain the efficacy of nerve coaptation by laser tissue
      welding in comparison to micro-sutures. In a first series of 15 rats, peripheral
      nerves were transsected. 24 nerves were coaptated by laser welding (LW) with
      different parameters in order to evaluate the optimal laser settings. For
      comparison, six nerves were coapted (NS) with four 10/0 nylon sutures. Finally,
      the nerves were removed and the tensile strength of the different coaptations
      determined. The best results of the laser welds were obtained at laser settings
      of 40 to 60 mW in the continuous mode resulting in a tensile strength of 9.5 +/-
      2.2 g. The tensile strength was 39.3 +/- 7.3 g for the sutured coaptation. In a
      second series, one sciatic nerve was coapted in thirteen rats by laser welding
      (LW) (60 mW, cont. mode) and in eleven rats using four 10/0 nylon sutures (NS).
      After six months, the Sciatic Function Index (SFI) was evaluated and the nerves
      were harvested for histological examination of transverse and longitudinal
      sections. All animals showed good regeneration and none of the 24 nerve
      coaptations showed dehiscence. The SFI was for the NS-group -94 +/- 23 and for
      the LW-group -77 +/- 20. The mean number of myelinated nerve fibres (NS 10,170 +/
      2512 vs. LW 11,902 +/- 1649) and the fibre diameter (NS 4.30 +/- 0.14 um vs. LW
      4.02 +/- 0.59 microns) of the nerves distal to the coaptation were similar in
      both groups and showed no statistical difference. We conclude that nerve
      coaptation by CO2-laser welds are as successful as the 10/0 nylon sutures in the
      animal model. Improvements of welding techniques may in the future reduce nerve
      damage even further and so yield even better functional results.

PMID- 9592700
TI  - [Granulomatous tumor of the flexor tendon sheath as first manifestation of
      sarcoidosis].
AB  - While osseous tumors of the phalanges are more common, soft-tissue manifestations
      in the hand are uncommon in patients with sarcoidosis. Our patient presented with
      a large but painless tumor on the palmar aspect of the right index finger
      limiting finger flexion. Histology of a biopsy specimen was interpreted as a
      granuloma of sarcoidosis. Further X-ray investigations revealed large bilateral
      formations in the hila of the lung interpreted as stage I sarcoidosis in an
      otherwise healthy individual. Tuberculosis and polyarthritis were excluded by
      standard tests. The tumor was then radically excised, as it was located within
      the flexor tendon sheath. After uneventful wound healing the patient had regained
      full function of his finger at six weeks follow up. Interestingly enough, a chest
      film at that time showed the hilar changes to have decreased as well, which is
      considered quite typical for this disease.

PMID- 9592701
TI  - A new personal technique of tendon graft reconstruction for gamekeeper's thumb
      using interference screw.
AB  - A new method for the reconstruction of chronic ulnar collateral ligament
      instability of the metacarpophalangeal joint is described. Reconstruction with
      our method using interference screw, adequately maintains both anatomical fiber
      direction and physiological tension in the grafted ligaments of adequate strength
      to reduce the immobilization period.

PMID- 9592702
TI  - [Interdisciplinary status of plastic, esthetic and reconstructive surgery in
      Austria].
AB  - To evaluate the actual status of interdisciplinary treatment involving plastic
      surgery in Austria in 1993 and 1994, standardised questionnaires were sent to all
      Departments of Plastic Surgery and to 129--mainly surgically orientated--medical
      departments in Vienna. The survey revealed that more than 50 percent of
      interdisciplinary co-operation took place with the departments of traumatology,
      general surgery and dermatology. The demand for co-operation with plastic
      surgeons was especially felt in tumor surgery, peripheral nerve surgery and hand
      surgery. An additional demand for co-operation represented larger soft tissue
      defects and congenital anomalies.

PMID- 9592705
TI  - [The role of endothelial function for ischemic manifestations of coronary
      atherosclerosis].
AB  - The vascular endothelium controls vasomotor tone by releasing a number of
      substances like nitric oxide (NO). NO has been shown to play a very important
      role, because it mediates vasodilation and furthermore inhibits platelet
      aggregation, expression of adhesion molecules for monocytes and adhesion of
      neutrophils and it impairs growth of vascular smooth muscle cells. An increased
      oxidative stress, decreasing the bioavailability of NO, is mainly responsible for
      a blunted endothelium dependent vasoreactivity. Risk factors for endothelial
      dysfunction are coronary artery disease, hypertension, hypercholesterolemia,
      smoking, and aging. Endothelial dysfunction in the presence of these risk factors
      might contribute to the occurrence of myocardial ischemia, aggravate acute
      coronary syndromes and accelerate progression of coronary artery disease.
      Amelioration of blunted endothelial function appears to be a major therapeutical
      goal to reduce ischemia and clinical events and might even retard progression of
      coronary artery disease.

PMID- 9592703
TI  - [Pathomorphology of coronary atherosclerosis].
AB  - The "American Heart Association Committee on Vascular Lesions" suggests the
      following morphologic classification of atherosclerotic plaques: the
      classification is based on large autopsy studies facilitating the assessment of
      the natural course of atherosclerotic lesions at precisely defined progression
      prone areas of the coronary tree from their clinically silent beginning to the
      stage where they produce symptoms. Lesion evolution is divided in 5 phases
      reflecting the possible time course of plaque development. Each phase is
      characterized by plaques with a distinctive morphology. The classification offers
      a framework of typical morphologies which the results of clinical investigations
      may be related to. Looking at the plaque composition, it is readily conceivable
      that atherosclerosis shares many characteristics with the general pathology of
      chronic inflammation and wound healing. Clinical symptoms e.g. acute coronary
      syndromes, arise from inflammation-mediated endothelial erosion and/or plaque
      rupture with ensuring coronary thrombosis. Advanced or complicated plaques are
      composed of different kinds of constituents in varying proportions. However,
      plaques at risk display a large lipid core occupying more than 40% of the
      plaque's volume, increased numbers of macrophages, reduced numbers of smooth
      muscle cells, an increased expression of tissue factor, and a thin plaque cap.
      Functionally, active plaques are characterized by a locally enhanced
      vasoreactivity with evidence coming from our own recent investigations that
      localised chronic inflammatory processes within the atherosclerotic plaque are
      responsible not only for the plaque rupture itself, but also for the
      hyperreactivity of these vessels to vasoconstrictor stimuli. In this context
      endothelin 1 (ET-1), a very potent vasoconstrictor peptide, may play an important
      role. ET-1 was originally reported to be produced by endothelial cells and to act
      locally in a paracrine fashion to regulate vascular tone. However, further
      studies have clarified that ET-1 is not only produced by endothelial cells but
      also by human inflammatory cells suggesting a role for ET-1 in inflammatory
      processes. Additionally, ET-1 displays a potent mitogenic activity. We examined
      immunohistochemically the presence of ET-1 in coronary plaque tissue obtained by
      directional coronary atherectomy. ET-1 immunoreactivity preferentially localized
      in plaque components indicative of a chronic inflammatory process. In addition,
      semiquantitative analysis of ET-1-like immunoreactivity revealed significantly
      higher staining grades in active coronary lesions compared with nonactive
      lesions. The increased ET-1 content in active coronary lesions may be beneficial
      to the stabilization of the vessel wall after plaque rupture and disadvantageous
      because it may lead to vasospasm and to the progression of atherosclerosis.

PMID- 9592704
TI  - [Methods for coronary functional assessment].
AB  - Functional evaluation of coronary vasomotion encompasses the assessment of
      dynamic changes in coronary lumen, vessel wall, blood flow, intracoronary
      pressure and myocardial perfusion in response to specific pharmacologic stimuli.
      These parameters are obtained to characterize mechanisms of physiologic
      regulation and to evaluate pathophysiologic processes and potential therapeutic
      strategies, especially with regard to the development of coronary
      atherosclerosis. To this end, a variety of direct (invasive) and indirect (non
      invasive) diagnostic tools are employed. Among the invasive methods are
      registration of intracoronary Doppler flow, coronary pressure measurements,
      quantitative coronary angiography and intravascular ultrasound. The non-invasive
      modalities consist of coronary Doppler echocardiography, positron emission
      tomography, myocardial scintigraphy and magnetic resonance imaging. Because of
      the different technical and physiological principles involved, these methods are
      complementary by providing independent access to different aspects. The combined
      invasive functional testing as employed in the cardiac catheterization laboratory
      allows for a simultaneous synopsis of high-resolution coronary imaging and direct
      measurement of physiologic parameters during local application of defined
      pharmacologically active substances. However, the demands in terms of equipment,
      time and operator skills are high and limit this combined invasive approach to
      specialized centers. Besides these research purposes, a number of functional
      methods has entered the clinical arena. They are employed to evaluate the
      hemodynamic significance of coronary lesions and to assess functional outcome of
      therapeutic interventions in the catheterization laboratory. The underlying
      principles and applications of the different methods are described and an
      overview of selected results is presented.

PMID- 9592706
TI  - [Coronary spasm--a clinically relevant problem?].
AB  - Coronary spasms are defined as reversible coronary stenosis, which limits
      coronary blood flow under resting conditions. The demonstration of either
      spontaneous or provoked coronary spasm proves coronary hypercontractility and
      thus the diagnosis of variant angina. Several stimuli can provoke coronary
      vasospasm, but the highest sensitivity and specificity has been shown with
      ergonovine. Alternatively acetylcholine or with less sensitivity, but high
      specificity, hyperventilation may be employed. Typically coronary vasospasm
      presents with angina pectoris at rest; the manifestation with myocardial
      infarction or syncope are of great clinical importance. The prevalence of the
      disease is unknown due to the rarely performed provocation tests in Western
      countries. The incidence of positive test results strongly depends on the
      symptoms of the patients; from 0% in patients without any evidence for myocardial
      ischemia up to 54% in patients with typical angina at rest have been observed.
      Coronary vasospasm is closely related to atherosclerotic coronary artery disease,
      since intravascular ultrasound studies reveal atherosclerotic plaques in almost
      any spastic segment. Risk factors for coronary artery disease and coronary
      vasospasm, however, differ profoundly. For the latter cigarette smoking is the
      only established risk factor. Although several candidates and predisposing
      factors (serotonin, histamine, thromboxane, endothelin) have been described, the
      mediators and the pathogenesis of the disease remains unknown. Endothelial
      dysfunction alone is not sufficient to explain the features of variant angina.
      Some evidence supports the hypothesis of local inflammation. The mortality in
      variant angina depends on the extent of the coronary artery disease. Pure
      coronary vasospasm does not lead to increased mortality; patients with highly
      active disease presenting with syncope may have an increased risk. Medical
      treatment should include long-acting calcium antagonists or nitrates, beta
      blockers may even favor the occurrence of ischemic attacks. Although the benefit
      has not been proven, the use of aspirin may considered in highly active disease.

PMID- 9592708
TI  - [Analysis of forearm circulation--a substitute for diagnosis of coronary
      atherosclerosis?].
AB  - The vascular endothelium plays a central role in the regulation of the arterial
      tone and in the control of the local hemostasis. It is also involved in the
      regulation of proliferation processes of the vascular wall. The presence of risk
      factors for coronary artery disease and/or manifest atherosclerotic lesions are
      associated with an impairment of endothelium-dependent vasoregulation. Since the
      assessment of coronary vascular reactivity requires an invasive approach, it
      would be desirable to non- or semi-invasively evaluate blood flow regulation and
      its impairment by atherosclerotic processes. Indeed, endothelial dysfunction of
      the coronary arteries parallels endothelium-related impairment of vasoreactivity
      of the brachial artery. Analysis of flow-dependent dilatation of the brachial
      artery by means of ultrasound represents a non-invasive diagnostic tool to assess
      endothelium-mediated vasomotion. By means of venous strain gauge forearm
      occlusion plethysmography, it is possible to measure the blood flow in a semi
      invasive way. The endothelium-mediated forearm blood flow response is obtained by
      the infusion of acetylcholine into the brachial artery, whereas infusion of
      sodium-nitroprusside provides information about the endothelium-independent
      vasodilator capacity of the forearm resistance vasculature. Assuming that the
      atherosclerotic process is a generalized disease, the assessment of the forearm
      blood flow by venous strain gauge occlusion plethysmography may provide some
      information applicable to the coronary circulation. However, the proof of a
      positive correlation between the degree of the impaired forearm blood flow
      responses measured by occlusion plethysmography and the extent of coronary
      atherosclerosis and its disturbed vasoregulation remains to be established.

PMID- 9592709
TI  - [Ambulatory catheter ablation. Indications, results and risks].
AB  - The purpose of this study was to test the efficacy, feasibility, and safety of
      outpatient radiofrequency catheter ablation in 162 consecutive patients. There
      were 83 men and 79 women at a mean age of 47 + 15 years; 13 patients underwent 2
      and 1 patient 3 ablation procedures. In 167 cases patients suffered from highly
      symptomatic paroxysmal tachycardia associated with presyncope or syncope in 74.
      Severe palpitations were present in 7 cases and recurrent syncope in 1 case. One
      patient had an asymptomatic Wolff-Parkinson-White syndrome with a shortest RR
      interval during atrial fibrillation of 150 ms. The mechanism of tachycardia was
      found to be atrioventricular nodal reentry in 78 cases, atrioventricular reentry
      involving an accessory atrioventricular pathway in 56, atrial fibrillation in 16,
      atrial flutter of the common type in 15, ectopic atrial tachycardia in 8, and
      idiopathic ventricular tachycardia in 3. Catheter ablation was performed in these
      176 cases at an overall success rate of 86%. In 148 cases patients could be
      treated on an outpatient basis and were discharged after a maximal observation
      time of 3 hours in 28, and 24 hours in another 120 cases. Short-term follow-up
      was uneventful in these patients. After 28 ablation procedures patients had to be
      admitted to the hospital, because of pain at the puncture sites or after
      pacemaker implantation in 15 cases, because of minor complications in 12, and
      because of pericardial tamponade in 1 case. Another severe complication occurred
      in 1 patient after successful ablation of right atrial tachycardia. Three days
      after discharge the patient suffered from pulmonary embolism originating from a
      thrombus at the ablation site. After hospital admission the patient recovered
      completely. In general, complication rate was 2.27%. This study shows that
      catheter ablation can be performed effectively and safety on an outpatient basis.

PMID- 9592707
TI  - [Therapeutic options for improvement of myocardial perfusion in coronary
      atherosclerosis].
AB  - The combination of morphological atherosclerotic alterations of coronary vessels
      and disturbance of coronary vasomotor control of epicardial and resistance
      vessels determines the amount of myocardial oxygen supply. The endothelium plays
      a crucial role for functional alterations of the coronary vessels in patients
      with early atherosclerosis or risk factors for coronary artery disease. A therapy
      which aims to ameliorate endothelium-dependent vasodilator capacity improves
      myocardial perfusion in patients with coronary artery disease. Thereby, even in
      patients with angiographically normal or minimally diseased coronary vessels who
      develop myocardial ischemia due to microvascular disease, symptomatic improvement
      might be achieved. Control of coronary vasomotor tone and proliferation processes
      within the vessel wall are both determined by the redox equilibrium of nitric
      oxide (NO) and superoxide radicals (O2-), induced by angiotensin II. Thus,
      vasomotor control and vessel wall proliferation is closely related to each other.
      Aim of a therapeutic intervention to enhance NO bioactivity is either to increase
      NO production in the endothelium or to decrease O2- production, which rapidly
      inactivates NO. NO bioactivity can be ameliorated by ACE-inhibitors, increase of
      shear stress on the endothelium by physical exercise, estrogens or L-arginine.
      For these therapies clinically an improvement of endothelial vasodilator function
      could be shown. In addition, improvement of endothelial vasodilator function can
      be achieved by a treatment which reduced oxidative stress in the vascular wall
      such as antioxidants and, especially, lipid lowering drugs. Endothelin
      antagonists and angiotensin II receptor-blockers are promising to improve
      endothelial dysfunction. However, these therapies have to be validated. Most
      therapy strategies, which have shown to ameliorate endothelial dysfunction, are
      also able to improve prognosis of the patients. Whether endothelial dysfunction
      alone--without evidence of overt coronary atherosclerosis--is sufficient to
      justify a long-term therapy to improve prognosis, still has to be clarified.

PMID- 9592710
TI  - Partial protection of severe combined immunodeficient mice against infection with
      Babesia microti by in vitro-generated CD4+ T cell clones.
AB  - Because CD4+ T cells were considered to be involved in protection against
      infection with Babesia microti, specific CD4+ T cells were generated in vitro
      from recovered BALB/c mice and their protective activity was tested in vivo. The
      cells produced varying amounts of interferon (IFN)-gamma in vitro in response to
      parasite antigen. In passive transfer experiments, three out of eleven T cell
      clones tested exerted protective activity in the early phase after infection.
      However, there seemed to be no correlation between this protection and in vitro
      IFN-gamma production by the T cell clones. Although the protection was partial
      and short-lived, the result provided direct evidence that CD4+ T cells play a
      crucial role in defense against B. microti.

PMID- 9592711
TI  - Histological changes in mouse nipple tissue during the reproductive cycle.
AB  - To obtain detailed information about the histological changes occurring in the
      mouse nipple during the reproductive cycle, we examined and quantified the S
      phase of cell by immunohistochemical staining with bromodeoxyuridine (BrdU), and
      analysed histologically the subepithelial fibrous elements. The nipple markedly
      increased in size dramatically on days 15-18 of pregnancy. The densities of cells
      in the epidermis and dermis were very high during the early stages of pregnancy
      but low during lactation. In the epithelium of the lactiferous sinus, the
      densities of cells did not differ significantly among stages. The BrdU antibody
      labeling revealed a number of BrdU-positive cells in the basal layer of the
      epidermis and epithelium of the lactiferous sinus. The ratios of BrdU-positive
      cells to total cells in the epidermis and the epithelium of the lactiferous sinus
      were highest on day 15 and day 10 of pregnancy, respectively. After lactation,
      however, the ratios were similar to those in the virgin stage. No significant
      differences were detected in the dermis among all stages. The number of collagen
      and elastic fibers increased during lactation. These results indicate that cells
      in the epidermis and lactiferous sinus proliferated actively from day 10 to day
      15 of pregnancy. The observation that cellular proliferation in the epithelial
      system of the nipple was stimulated at the early stage of pregnancy, while the
      dermis has two growth phases, with cellular proliferation during pregnancy and an
      increase in extracellular matrix during lactation, suggests that these two
      phenomena might be regulated by different factors.

PMID- 9592712
TI  - Lipoprotein profile in canine pancreatitis induced with oleic acid.
AB  - Lipid and lipoprotein concentrations and apolipoprotein profile were investigated
      in canine pancreatitis induced by infusion with oleic acid (OA) into the
      accessory pancreatic duct. Pancreatitis was diagnosed by physical, hematological,
      biochemical and pathological examinations. In OA-treated dogs, serum triglyceride
      (TG) concentration was increased; however, there were no changes in serum total
      cholesterol (TC) and phospholipid (PL) concentrations. Serum concentrations of
      TG, TC, PL and total lipids (TL) in beta lipoprotein and those of TC, PL and TL
      in pre-beta lipoprotein were increased and those of TC, PL and TL in alpha,
      lipoprotein were decreased. In apolipoprotein profile, the proportions of
      apolipoprotein B100 in low density lipoprotein fraction and apolipoprotein A-IV
      in high density lipoprotein fraction were increased. In addition, decreased
      proportion of apolipoprotein A-I and the appearance of serum amyloid A protein in
      high density lipoprotein fraction were observed. These results suggest that
      lipoprotein profiles observed in canine acute pancreatitis are attributed to the
      alterations in apolipoprotein compositions.

PMID- 9592713
TI  - Development of in vitro fertilized feline embryos in a modified Earle's balanced
      salt solution: influence of protein supplements and culture dishes on
      fertilization success and blastocyst formation.
AB  - The effects of protein supplements and culture dish type on in vitro
      fertilization (IVF) and embryo development in culture were examined in the
      domestic cat. In Experiment I, follicular oocytes were fertilized and cultured in
      either 1) modified Earle's balanced salt solution, designated MK-1, supplemented
      with one of the following: 10% human serum (HS), 10% FCS or 0.4% BSA, or 2)
      Medium 199 (M-199) supplemented with 10% FCS. Fertilization rates were lower (P <
      0.01) in MK-1 + BSA (74.4%), MK-1 + FCS (56.1%), and M-199 + FCS (51.4%) than in
      MK-1 + HS (94.7%). A greater (P < 0.01) percentage of blastocysts was obtained in
      MK-1 + HS (50.0%) than in other treatment groups (range, 4.3-17.2%). In
      Experiment II, the effect of dish type (tissue culture dish, TCD, versus
      suspension culture dish, SCD) on embryo development was evaluated in MK-1
      supplemented with either HS or BSA. Significantly higher proportions of IVF
      derived embryos developed to blastocysts at 120 and 144 hr post-insemination,
      respectively, when cultured in HS/SCD (47.2 and 71.7%) than in BSA/SCD (11.4 and
      27.3%) or BSA/TCD (10.4 and 25.0%). At 120 hr post-insemination, there was a
      lower (P < 0.01) percentage of blastocysts in HS/TCD (22.2%) than in HS/SCD. In
      Experiment III, six embryos per cat were transferred to the uterine horns of 17
      recipients at 144 hr after hCG treatment. Five of 7 recipients which received
      late morulae cultured in MK-1 + BSA (SCD) for 120 hr became pregnant (71.4%).
      Eight of 10 recipients which received early blastocysts cultured in MK-1 + HS
      (SCD) for 120 hr became pregnant (80.0%). We conclude that MK-1 containing HS is
      highly beneficial for overcoming the in vitro developmental block of IVF-derived
      feline embryos and increasing the success rate of IVF/ET.

PMID- 9592714
TI  - Effects of glutamine, glycine and taurine on the development of in vitro
      fertilized bovine zygotes in a chemically defined medium.
AB  - The effects of glutamine, glycine and taurine on the development of bovine
      zygotes derived from IVM/IVF were determined using a protein-free chemically
      defined medium. After the cumulus cells were removed at 18 hr post-insemination,
      the presumptive zygotes were cultured for 4 or 6 days (about 104 or 154 hr) under
      a gas atmosphere of 5% O2: 5% CO2: 90% N2. A modified synthetic oviduct fluid
      medium supplemented with 20 amino acids (1 mM glutamine, essential amino acids
      for basal medium Eagle and non-essential amino acids for minimum essential
      medium), insulin, and PVA was used as a basic medium (mSOFai). Omitting 1 mM
      glutamine from mSOFai did not affect the embryonic development after 4 and 6 days
      of culture. After 4 days of culture, no significant effects of glycine and
      taurine on the development of zygotes to the morula stage were observed. However,
      supplementation with glycine or taurine significantly (P < 0.05) affected, with
      no interaction, the embryonic development to blastocysts after 6 days of culture.
      Addition of 5 mM glycine and 2 or 10 mM taurine significantly (P < 0.05)
      increased the percentage of blastocysts. The mean cell number in the blastocysts
      was affected by the glycine level, and was increased by the addition of 10 mM
      glycine (P < 0.001). These results demonstrate that glycine and taurine in a
      chemically defined medium containing a group of essential and non-essential amino
      acids improve the development of bovine zygotes to the blastocyst stage under 5%
      O2.

PMID- 9592715
TI  - Influence of thiouracil-induced hypothyroidism on adrenal and gonadal functions
      in adult female rats.
AB  - The effect of hypothyroidism on adrenals and gonads in adult female rats was
      investigated throughout the estrous cycle. Hypothyroidism was induced by
      administration of 4-Methyl-2-Thiouracil (Thiouracil) in the drinking water. The
      weight of ovaries and adrenals, and the plasma levels of corticosterone decreased
      in hypothyroid rats as compared with euthyroid rats throughout the estrous cycle.
      Hypothyroidism resulted in decreased concentrations of plasma LH on the day of
      diestrus and proestrus, whereas the plasma concentrations of prolactin and
      progesterone increased as compared with euthyroid rats. The weight of uteri and
      plasma concentrations of estradiol decreased during the day of diestrus and
      proestrus in hypothyroid rats as compared with euthyroid rats. To further clarify
      the dysfunction of hypothalamo-hypophysial-adrenal axis in hypothyroid rats,
      animals were stressed by immobilization for 3 hr. In hypothyroid rats, a marked
      increase in plasma levels of ACTH in response to immobilization stress was
      observed compared to euthyroid control, whereas increases in plasma
      concentrations of corticosterone were much smaller in hypothyroid than euthyroid
      rats. These results clearly indicate that hypothyroidism causes both gonadal and
      adrenal disturbances in adult female rats. The increased concentrations of plasma
      progesterone may be due to hypersecretion of prolactin during the day of
      proestrus and estrus, which in turn result in disruption of the estrous cycle.

PMID- 9592716
TI  - Effect of heparin on hemagglutination by equine arteritis virus.
AB  - Heparin inhibited hemagglutination (HA) by equine arteritis virus (EAV) as well
      as did HA by Aujeszky's disease virus (ADV), but failed to inhibit HA by
      parainfluenza virus type 3 (PIV-3). The minimal concentration of heparin required
      to inhibit 8 HA U of EAV was 0.1 U/ml. In addition, most EAV hemagglutinin was
      retained by heparin acrylic beads, as was ADV hemagglutinin, but was not PIV-3
      hemagglutinin. Mouse erythrocytes failed to combine with the HA inhibitory factor
      of heparin. However, mouse erythrocytes treated with heparinase had greatly
      reduced agglutinability by EAV. All these findings suggest that a heparin-like
      molecule on the surface of mouse erythrocytes serves as the virus-cell receptor.

PMID- 9592717
TI  - Repair of ulnar segmental defect by recombinant human bone morphogenetic protein
      2 in dogs.
AB  - The efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined
      with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) as a
      carrier on the repair of segmental long-bone defects was evaluated using an ulnar
      model in dogs. The defect was 2 cm in length and was fixed with bone plating.
      After implantation of PGS with or without rhBMP-2, the repair process of the
      defect was evaluated by serial radiography until 16 postoperative weeks. All
      defects treated with 160 micrograms or 640 micrograms of rhBMP-2/PGS revealed
      bone union radiographically by 12 postoperative weeks, whereas all defects
      treated with PGS alone revealed no radiographic evidence of healing throughout
      the experimental period. In defects treated with 40 micrograms of rhBMP-2/PGS,
      new bone appeared partially at the defects but did not accomplish union. Bone
      mineral contents at the defect sites after harvest at 16 weeks postoperatively
      were significantly (p < 0.05) higher in those treated with 160 micrograms or 640
      micrograms of rhBMP-2 than in those treated with 40 micrograms of rhBMP-2 or PGS
      alone. Histologically, defects radiographically diagnosed as having achieved
      union showed the appearance of cortical bone and bone marrow cells. These
      findings suggest the use of rhBMP-2/PGS as a potential bone graft substitute in
      reconstructive surgery in dogs.

PMID- 9592718
TI  - Anti-obesity effects of selective agonists to the beta 3-adrenergic receptor in
      dogs. I. The presence of canine beta 3-adrenergic receptor and in vivo
      lipomobilization by its agonists.
AB  - It is known that in rodents and humans the beta 3-adrenergic receptor (beta 3-AR)
      is present primarily in adipocytes and plays a significant role in the adrenergic
      stimulation of lipolysis. We examined the expression of beta 3-AR mRNA in the dog
      and the lipomobilizing effects of beta 3-AR-selective agonists in vivo. Reverse
      transcription polymerase chain reaction of RNA extracted from dog adipose tissue
      produced a cDNA fragment, the nucleotide sequence of which was highly homologous
      to the corresponding regions of human (86.4%) and mouse (79.5%) beta 3-AR cDNA.
      The beta 3-AR mRNA was present at high levels in subcutaneous and visceral
      adipose tissues, but undetectable in other organs. When a selective beta 3-AR
      agonist, CL316,243, was infused intravenously into beagle dogs, the plasma level
      of free fatty acid increased in 30 min and persisted at higher levels for several
      hours. ICI D7114, another beta 3-AR agonist, also showed a similar lipomobilizing
      effect, but with lower potency. beta 3-AR agonist infusion also increased the
      plasma insulin level. These results suggested that functional beta 3-AR is
      present in adipose tissues of the dog and that it is effective for in vivo
      lipomobilization.

PMID- 9592719
TI  - Anti-obesity effects of selective agonists to the beta 3-adrenergic receptor in
      dogs. II. Recruitment of thermogenic brown adipocytes and reduction of adiposity
      after chronic treatment with a beta 3-adrenergic agonist.
AB  - The aim of this study was to evaluate the effectiveness of beta 3-adrenergic
      agonists for the treatment and prevention of obesity in the dog. When a selective
      beta 3-adrenergic agonist, CL316,243 (0.1 mg/kg), was given orally to adult
      beagles every day for 5-7 weeks, body weight and girth were decreased compared
      with control placebo-treated dogs. Gross anatomical examinations revealed no
      noticeable abnormalities in CL316,243-treated dogs, except an apparent decrease
      in abdominal fat. Immunohistochemical examination of perirenal adipose tissue
      showed a remarkable increase in brown adipocytes expressing a thermogenic
      protein, uncoupling protein (UCP). The increased expression of UCP and its mRNA
      in CL316,243-treated dogs was also confirmed by Western blot and reverse
      transcription polymerase chain reaction analyses. It was concluded that treatment
      with a beta 3-adrenergic agonist stimulates UCP expression, which may lead to an
      increase in energy expenditure, and thereby is useful for the treatment and
      prevention of obesity in the dog.

PMID- 9592720
TI  - Detection of retinyl palmitate and retinol in the liver of mice injected with
      excessive amounts of retinyl acetate.
AB  - The transport of subcutaneously injected retinyl acetate (RA, 100,000 IU/mouse,
      105,470 nM) was investigated in male ICR mice (10-week-old) at 0, 3, 6, 12, 18,
      24 and 72 hr after a single injection. The retinol and retinyl palmitate levels
      of liver homogenates, bile in the gallbladder and serum from peripheral blood
      were measured by high performance liquid chromatography (HPLC) method. Retinyl
      palmitate in the lipid droplets of hepatocytes and Ito cells was localized by a
      modified gold chloride staining method. Accumulation of retinyl palmitate peaked
      at 12 hr post-injection and decreased thereafter until 24 hr post-injection.
      Fluorescence microscopy revealed many fluorescent vitamin A-containing lipid
      droplets in hepatocytes around central veins at 12 hr post-injection, but such
      droplets were not observed in the vehicle control mice or at in the RA-injected
      mice after 18 hr of injection. Electron microscopic observation also indicated
      that many retinyl esters-containing lipid droplets were observed in hepatocytes
      around the central veins at 12 hr post-injection, but no droplets were seen in
      the controls or 18 hr post-injection. The retinyl palmitate levels in liver
      homogenates assessed by HPLC decreased from 12 to 24 hr post-injection and
      increased significantly in bile, while retinol in liver homogenates and serum
      markedly increased. One of the morphological alterations was intense
      vacuolization in hepatocyte cell cords from the portal toward the central vein
      observed at 24 hr post-injection. Transitional lipid droplets between vacuoles
      and lipid droplets were identified in those hepatocytes. These results of HPLC
      analysis of retinol and retinyl palmitate in liver homogenates, serum, and bile,
      together with the results of gold chloride staining suggested that subcutaneously
      injected RA was first incorporated in hepatocytes at 12 hr and then partially
      metabolized through vacuoles, transferred into the blood and secreted into the
      bile over a 24 hr period. Many retinyl esters-containing lipid droplets were
      visualized in Ito cells at 72 hr post-injection. Most of vitamin A in the liver
      homogenates measured by HPLC was retinyl palmitate. Therefore, the contents in
      those lipid droplets might be retinyl palmitate.

PMID- 9592721
TI  - Tonic block of the sodium and calcium currents by ketamine in isolated guinea pig
      ventricular myocytes.
AB  - Effects of ketamine on the sodium (INa) and L-type calcium currents (ICa) were
      examined by using whole-cell patch clamp techniques in guinea pig single
      ventricular myocytes. The mode of action of ketamine was compared with those of
      quinidine, a sodium channel blocker, and verapamil, a calcium channel blocker.
      Ketamine (30-300 microM) inhibited both INa and ICa in a concentration-dependent
      manner. Quinidine (30 microM) and verapamil (0.1 microM) produced use-dependent
      depression of INa and ICa, respectively. The amplitude of INa elicited by the
      first depolarizing pulse after a long quiescent period was slightly decreased by
      quinidine. During a train of depolarizing pulse the current amplitude decreased
      gradually, and reached a steady state level in the quinidine-treated cell (use
      dependent block, UDB). Verapamil produced a similar mode of inhibition of ICa,
      i.e., UDB. In contrast, ketamine produced significant decrease in INa and ICa
      elicited by the first depolarizing pulses and the decreases of both currents were
      not augmented during a train of depolarizing pulses. From these results, it can
      be concluded that ketamine produces tonic block of the cardiac sodium and calcium
      channels and the mode of inhibition is clearly different from UDB by quinidine
      and verapamil.

PMID- 9592722
TI  - Energy dispersive X-ray fluorescence spectrometry of major tissues of silky
      fowls.
AB  - This report is to survey elements in frozen or freeze-dried samples of major
      organs of silky fowls with energy dispersive X-ray fluorescence spectrometer
      (EDXRF). There was not essential difference between frozen and freeze-dried
      samples. Of major elements, P. S, K, and Cl were always detected and Mn, Fe, Ca,
      and Zn were detectable in certain organs. Iodine was detected in thyroid glands.
      Occasionally Br was detected. The duration of freeze drying, 24 hr or 7 days, did
      not make significant difference in elemental analysis.

PMID- 9592723
TI  - The surface color measurement of major tissues of silky fowls and White Leghorns.
AB  - This report concerns the surface color of major organs of the silky fowl and
      White Leghorn chicken as measured by a color analyser. Although it is obvious
      that organs of the silky fowl look darker than those of the white leghorn, the
      color measurement of these organs has not yet been reported. The authors found
      that color differences between silky fowls and White Leghorns were significant in
      lung, brain, skin, and gluteal muscle. But the surface color of kidney and
      cardiac muscle of the two groups of fowl was not significantly different. The
      present data were represented in color charts.

PMID- 9592724
TI  - Cloacal inoculation with the Connecticut strain of avian infectious bronchitis
      virus: an attempt to produce nephropathogenic virus by in vivo passage using
      cloacal inoculation.
AB  - Avian infectious bronchitis virus (IBV) strain Connecticut A-5968 isolated from
      respiratory tissue of chickens in USA in the 1960s, is considered as
      representative of respiratory disease causing IBV strains. Specific pathogen free
      chicks inoculated with the strain via the cloaca replicated the virus more
      rapidly in their kidneys than did chicks inoculated with the same virus
      intratracheally. Virus passaged thirteen-times via the cloaca caused stronger
      nephrotropism and nephropathogenicity than the parent virus. It is suggested that
      cloacal inoculation of IBV provides new and interesting information concerning
      the mechanisms of nephropathogenicity of IBV which has became increasingly
      important worldwide during the last ten years.

PMID- 9592725
TI  - Potentiated decrease of plasma folate levels caused by the coadministration of
      folic acid in rats treated with methotrexate.
AB  - The decrease of plasma 5-methyltetrahydrofolic acid (5-MF) levels, postulated as
      an indicator of folate status, was studied following the administration of both
      methotrexate (MTX) alone and MTX with folic acid (FA) using rats as our
      experimental model. Blood and urine samples were serially collected over a 9 hr
      period after the administration of MTX, MTX with FA and from a control group to
      examine the plasma kinetics and the renal clearance of 5-MF. The pharmacokinetics
      of MTX and the plasma protein binding of 5-MF were also examined. The
      concentrations of these analytes were assayed using high performance liquid
      chromatography (HPLC). MTX administration produced decreased plasma 5-MF levels.
      This observed decrease was potentiated by oral FA administration, suggesting that
      the folate status was more severely altered by the coadministration of FA. The
      renal clearance of 5-MF also increased dose-dependently with FA (0.05-5 mg/kg)
      coadministration. The plasma protein binding of 5-MF was not affected by the FA
      administration, which indicates that the fraction of 5-MF that was filtered
      through the glomerular apparatus appeared to be unchanged. In addition, the
      pharmacokinetic profiles of MTX also appeared not to be affected by the addition
      of FA. We conclude that the inhibition of reabsorption of 5-MF in the renal tube
      by concurrent administration of MTX and FA must be one of the causal factors for
      the demonstrated decrease in the plasma 5-MF levels in rats.

PMID- 9592726
TI  - Establishment of Boophilus microplus infected with Babesia bigemina by using in
      vitro tube feeding technique.
AB  - The in vitro tube feeding technique is used to establish a laboratory colony of
      Boophilus microplus infected with Babesia bigemina. Pre-fed engorged female ticks
      offered 2 x 10(4) and 2 x 10(5)/ml of B. bigemina infected bovine red blood cells
      (RBC) showed sporokinetes in the haemolymph smear sample, and positive signals
      for B. bigemina in polymerase chain reaction (PCR). Larvae laid from the ticks
      offered 2 x 10(5)/ml of B. bigemina infected RBC showed evidence for B. bigemina
      infection in microscopic method and PCR. While larvae laid from the ticks offered
      2 x 10(4)/ml of B. bigemina infected RBC showed positive for B. bigemina in only
      PCR. The females offered 2 x 10(3)/ml B. bigemina infected RBC and their larvae
      did not show positive evidences for B. bigemina infection. It is thought that the
      in vitro tube feeding technique can be a convenient method to study the
      relationship between ticks and tick-borne pathogens. It is also suggested that
      the superior sensitivity of PCR compared to the microscopic method in detection
      of B. bigemina from the tick sample, especially in larvae.

PMID- 9592727
TI  - Prevention of orotic-acid-induced fatty liver in male rats by
      dehydroepiandrosterone and/or phenobarbital.
AB  - Dehydroepiandrosterone (DHEA) is a steroid hormone which induces the peroxisome
      proliferation in rodents. The fatty liver induced by orotic acid and a high
      sucrose diet in male rats was prevented by the administration of DHEA and/or
      phenobarbital (PB). A significant increase in the liver weight was induced in the
      DHEA group (relative weight) and the DHEA + PB group (absolute and relative
      weight). The liver weight increased more conspicuously in the DHEA + PB group
      than in the DHEA group. The increase in the liver weight was caused by an
      increase in the cell size and peroxisome number. In addition, the administration
      of DHEA alone and the combination of DHEA and PB prevented the lipid droplet
      accumulation in hepatocytes. The administration of PB alone also prevented the
      accumulation of lipid droplets without any increase in the liver weight.

PMID- 9592728
TI  - The effect of oligosaccharides on the production of tumor necrosis factor-alpha
      by macrophage-like cell line J774/JA-4.
AB  - Stimulation and modulation of tumor necrosis factor-alpha (TNF-alpha) production
      during treatment of the murine macrophage-like cell line J774/JA-4 with 25
      oligosaccharides were studied. Direct stimulation of TNF-alpha production by
      oligosaccharides was measured with a cytotoxic assay using the L929 cell line.
      Twelve samples showed a significantly higher production (P < or = 0.01) of TNF
      alpha than the controls. Modulation of TNF-alpha production by treatment with
      oligosaccharides, followed by stimulation with lipopolysaccharide (LPS) from E.
      coli, was examined using the L929 bioassay system. In three samples TNF-alpha
      production increased significantly, but in four samples, production was reduced
      significantly (P < or = 0.01). No samples showed modulation of growth or
      viability of L929 cells within the first 26 hr. The present results are useful in
      the application of these oligosaccharides which is potentially applicable in
      medical and food technology.

PMID- 9592729
TI  - Timing of completion of the first meiotic division in bovine oocytes after
      maintenance of meiotic arrest with cycloheximide and their subsequent
      development.
AB  - This study examined the timing of completion of meiosis I of bovine oocytes in
      which meiotic resumption had been inhibited by cycloheximide (CHX), and also
      determined the optimum interval of maturation in culture for subsequent
      fertilization and development. Most oocytes treated with CHX reached metaphase II
      at 16 hr in the maturation culture, while control oocytes did at 20 hr. CHX
      treated oocytes cultured for 16 hr were normally fertilized but failed to develop
      into blastocysts. Maturation in culture for 20 hr resulted in comparable
      development for control oocytes. The results indicate that nuclear maturation of
      CHX-treated oocytes was completed 4 hr faster than for control oocytes, however
      the same interval of maturation as that of control oocytes is necessary for
      subsequent development to blastocysts.

PMID- 9592730
TI  - Preliminary study of nematode infections of cattle in the six provinces of
      Thailand in the dry season.
AB  - Fecal nematode egg counts and serum pepsinogen concentrations of cattle were
      determined in six Provinces of the northern (Chiangrai and Lampang), north
      eastern (Khonkaen, Mahasarakham and Nakhonratchasima) and eastern (Chonburi)
      parts of Thailand in the dry season. Nematode eggs were detected in 82% of
      animals examined. Serum pepsinogen concentrations ranged from 78 to 2,951 (mean
      934) mU tyrosine. Animals in Chonburi Province had higher mean values for both
      egg counts and serum pepsinogen concentrations than animals in the other
      Provinces. Two calves in Khonkaen and Mahasarakham Provinces were found to be
      heavily infected with Strongyloides papillosus, with 10,840 and 9,593 eggs/g
      feces. The source and route of S. papillosus infections remained unknown.

PMID- 9592731
TI  - Evaluation of serological diagnosis of Borna disease virus infection using
      recombinant proteins in experimentally infected rats.
AB  - We produced two recombinant Borna disease virus (BDV) proteins, p40 and p24, by
      using a baculovirus vector as a diagnostic antigen. Antigenicities of these
      recombinant proteins were evaluated by immune rabbit sera. Recombinant p40 was a
      more sensitive antigen than p24 for the detection of antibodies in infected rats.
      Rats inoculated with BDV within 24 hr after birth showed higher detection rates
      of viral RNA and viral proteins from the brain than rats inoculated at 4 weeks
      old. Depending on the age of infection and the time postinfection, the detection
      of BDV RNA, protein, or anti-BDV antibody did not always correlate in
      individuals. We suggest both serological and molecular biological methods are
      needed in the diagnosis of BDV infection.

PMID- 9592732
TI  - Femoral nonunion fracture treated with recombinant human bone morphogenetic
      protein-2 in a dog.
AB  - This is the first report on successful treatment of spontaneous nonunion fracture
      of a dog by use of recombinant human bone morphogenetic protein-2 (rhBMP-2). A 4
      year-old Pomeranian dog with a 2-year history of femoral nonunion fracture was
      treated with implantation of rhBMP-2. The dog had received surgical correction
      twice prior to the admission but radiography of the affected limb revealed a
      typical figure of nonunion fracture. Glossly, the fractured ends were sclerotic
      and the area between the ends was filled with fibrous tissue. After debridement
      the femoral shaft was fixed by an 8-hole plate. rhBMP-2 at a total dose of 256
      micrograms was implanted with a synthetic carrier into the 8-mm defect formed by
      the debridement. Callus formation responding to rhBMP-2 was radiographically
      observed at 2 weeks after implantation and the defect reached radiographic union
      by 8 weeks after implantation. The plate was removed at 9 months after
      implantation. Any complications were not observed for 5 months after removal of
      the plate.

PMID- 9592733
TI  - Hemagglutination with crane herpesvirus.
AB  - A crane herpesvirus (CrHV) grown in chicken embryo fibroblast (CEF) cells was
      tested for hemagglutination (HA) with erythrocytes from a variety of species at 4
      degrees C, room temperature and 37 degrees C. HA was observed at all temperatures
      with erythrocytes from mouse, ddY and BALB/c strains, but not with those from
      cattle, sheep and chicken. Mice, ddY strain, showed an individual variation in
      agglutinability of their erythrocytes and erythrocytes from BALB/c gave a higher
      HA titer. The HA activity was inhibited by the sera obtained from naturally
      infected cranes, experimentally infected duck and immunized rabbit with CrHV. HI
      antibody titers of these sera showed a closely positive correlation with their
      neutralizing antibody titers.

PMID- 9592734
TI  - Expression of the glycoprotein E2 of the classical swine fever virus in
      Escherichia coli.
AB  - The glycoprotein E2 sequences of classical swine fever virus (strain p97) were
      cloned, sequenced and expressed in E. coli. Result from SDS-polyacrylamide gel
      electrophoresis analysis of expressed proteins revealed the presence of a
      prominently stained band corresponding to a molecular mass of 61 kDa, which is in
      agreement with the predicted size from the DNA sequence. The recombinant E2
      protein contained an aminoterminal tag of six histidines that could be used for
      purification by the nickel chelate affinity chromatography. The elution fractions
      of the expressed protein also contain additional bands of 40 and 35 kDa proteins,
      indicating proteolytic cleavages might occur. Our Western blotting result also
      supported that the expression of the recombinant E2 protein of the classical
      swine fever virus were accomplished.

PMID- 9592736
TI  - [Interview with Professor Dr. Heinrich Harms. Interview by Georg Mehrle].

PMID- 9592737
TI  - [Transplant vertical tilt after perforating keratoplasty--comparison between non
      mechanical trepanation with excimer laser and motor trepanation].
AB  - BACKGROUND: Besides decentration of the graft/host trephination and "horizontal
      torsion" "vertical tilt" is an important factor for reduced visual outcome after
      penetrating keratoplasty (PK). The purpose of this study was to evaluate the time
      course of vertical tilt in absolute value and direction and to correlate it with
      functional results after PK. PATIENTS AND METHODS: Fifty patients each (20
      primary dystrophies, 30 keratoconus) underwent nonmechanical trephination (NMT)
      (excimer laser MEL60, Aesculap-Meditec, Heroldsberg, Germany) or mechanical motor
      trephination (MT) (Geuder, Heidelberg, Germany) in penetrating keratoplasty. All
      procedures (7.5 mm in dystrophies, 8.0 mm in keratoconus, 8 orientation teeth in
      NMT, double-running 10-0 nylon suture) were performed by one surgeon (GOHN). At a
      postoperative gate of 6 weeks, 6 months, before partial suture removal and after
      complete suture removal, corneal topography analysis (TMS-1, Tomey, Tennenlohe,
      Germany) was performed. After a Gram-Schmidt-orthogonalization corneal topography
      height data of 25 noncentric rings in 256 hemimeridians were decomposed into
      Zernike components of radial order n = 16 in the sense of minimizing the root
      mean square error. The tilt of the surface relative to the videokeratoscope axis
      was calculated from the Zernike components Z1(1) and Z1(-1). The meridional power
      at the cardinal meridians was derived from all parabolic Zernike terms. Tilt and
      the difference between both meridians of the Zernike representation (ZA) were
      correlated with the results of Zeiss keratometry (KA). Simulated Keratometry
      (SimK) of the TMS-1, subjective refraction (RZ) and best-corrected visual acuity.
      RESULTS: After NMT, vertical tilt of the graft was 3 degrees without significant
      change over time. Following MT, an equivalent time course could be observed
      before partial suture removal. However, after complete suture removal, a
      significant increase of the tilt was measured to 5 degrees (p = 0.02). No
      significant difference could be detected comparing keratoconus and Fuchs'
      dystrophy both in NMT and MT. The direction of the vertical tilt component piled
      up to the hemimeridian defined by the knot of the first running suture. At all
      postoperative follow-up examinations, the ZA of the Zernike decomposition showed
      a good correlation to the RZ, whereas the KA and the SimK did not. At the end of
      the follow-up, best-corrected visual acuity after NMT was 2 decimal lines better
      than after MT. CONCLUSIONS: The Zernike decomposition of topographic height data
      is a suitable tool for extraction and quantifying vertical tilt of the graft
      following penetrating keratoplasty. In contrast to conventional keratometry with
      its 4-point measurement, a decomposition of topographic height data into
      orthogonal polynomials enables a detection of both cardinal meridians even in
      corneas with a high degree of local irregularities.

PMID- 9592738
TI  - [Value of optical coherence tomography in diagnosis of age-related macular
      degeneration. Correlation of fluorescein angiography and OCT findings].
AB  - BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of
      blindness in industrialized countries. In this study, we used optical coherence
      tomography for evaluation of patients with AMD. METHODS: Optical coherence
      tomography imaging is analogous to ultrasound, except that reflected light
      instead of sound is used. The analysis of the reflected light is processed with
      the technique of low-coherence interferometry. In this study, 33 patients with
      different stages of AMD were examined with optical coherence tomography. The
      classification of AMD was according to the guidelines as proposed by the
      "International ARM Epidemiological Study group". RESULTS: With this method we
      were able to identify drusen, alteration of the retinal pigment epithelium, and
      secondary retinal changes. Other structures such as basal laminar (linear)
      deposits could not be identified with this method. Choroidal neovascularization
      was evident in the tomogram. Classic choroidal neovascular membranes presented
      with well-defined boundaries on optical coherence tomography and occult choroidal
      neovascular membranes had a less delineable structure with optical coherence
      tomography. CONCLUSION: Optical coherence tomography cannot replace conventional
      diagnostic techniques. This method provides no additional information in patients
      with non-exsudative AMD. In patients with choroidal neovascular membranes
      secondary to AMD optical coherence tomography may be able to characterize the
      relation of the membrane to the retinal pigment epithelium and imaging may be
      possible through hemorrhage. The interpretation of the optical coherence tomogram
      needs further studies including clinicopathologic correlation.

PMID- 9592739
TI  - [Early posterior capsule fibrosis after combined cataract and vitreoretinal
      surgery with intraocular air/SF6 gas tamponade].
AB  - BACKGROUND: The surgical approach in treating coexisting vitreoretinal disease
      and cataract is controversial. We report on patients who developed early
      posterior capsular fibrosis after combined cataract and vitreoretinal surgery
      with air/SF6-gas tamponade. PATIENTS AND METHODS: The medical records of 15
      consecutive eyes (13 patients) who underwent combined phacoemulsification with
      intraocular lens implantation and vitreoretinal surgery with intraocular air/SF6
      gas tamponade were retrospectively analyzed. The indications for vitreous surgery
      included: subfoveal neovascular membrane in age-related macular degeneration (5
      eyes), macular hole (4 eyes), macular pucker (2 eyes), rhegmatogenous retinal
      detachment (2 eyes), persistent vitreous haemorrhage after branch retinal vein
      occlusion (1 eye), persistent vitreous haemorrhage and/or tractional retinal
      detachment in proliferative diabetic retinopathy (1 eye). The mean follow-up
      period was 7 months (1-13 months). A control group consisted of 15 eyes (15
      patients) who underwent the equal combined operation without intraocular
      tamponade. The indications for vitreous surgery were persistent vitreous
      haemorrhage in proliferative diabetic retinopathy (5 eyes), persistent vitreous
      haemorrhage after branch retinal vein occlusion (5 eyes), asteroid hyalosis (2
      eyes), macular pucker (1 eye), posttraumatic vitreous haemorrhage (1 eye), acute
      retinal necrosis (1 eye). The mean follow-up was 8 months (2-13 months). The
      posterior capsule was examined at the slit lamp microscopy with maximal dilated
      pupils. We defined posterior capsular opacification (PCO) as severe if posterior
      capsule was fibrotic, diffusely thickened and opaque. Modest PCO was
      characterized by focal fibrotic opacifications at otherwise clear posterior
      capsule. RESULTS: Severe posterior capsular fibrosis developed in 9 eyes (60%)
      after 2-14 weeks postoperatively (mean 8 weeks) including 3 of 6 eyes with air
      tamponade (50%) and 6 of 9 eyes with 20% SF6-gas tamponade (66.7%). In 6 eyes
      (40%) Nd:YAG-laser capsulotomy was performed 4-14 weeks postoperatively (mean 8.5
      weeks). In the control group modest PCO developed in 8 eyes (53.3%) 1-13 months
      postoperatively (mean 6.5 months) none requiring Nd:YAG-laser capsulotomy during
      follow-up period. CONCLUSIONS: Combined cataract and vitreoretinal surgery with
      intraocular air/SF6-gas tamponade induces severe posterior capsular fibrosis in
      the early postoperative period. The capsular fibrosis is presumably caused by
      accumulation of fibrin and proliferation stimulating factors in the narrow space
      between intraocular lens and air/SF6-gas bubble.

PMID- 9592740
TI  - [Type I lattice corneal dystrophy. Clinical and molecular genetic study of a
      large family].
AB  - BACKGROUND: Lattice corneal dystrophy type I is one of the frequent forms of
      stromal dystrophies following autosomal dominant inheritance. The beta-IG-h3 gene
      encoding keratoepithelin on the long arm of chromosome 5 has recently been
      described as disease gene for lattice corneal dystrophy type I as well as for
      three other corneal dystrophies with autosomal dominant pattern of inheritance.
      PATIENTS AND METHODS: Ten family members in three generations of a large family
      with autosomal dominant lattice corneal dystrophy were analyzed clinically by
      slit-lamp biomicroscopy. Mutation analysis in the beta-IG-h3 gene was carried out
      at the mRNA level by RT-PCR and cDNA sequencing. RESULTS: A heterozygous single
      base substitution (417C-->T) in exon 4 of the beta-IG-h3 gene was detected
      predicting the replacement of arginine-124 by cysteine. Analysis of 10 family
      members showed perfect cosegregation of the mutation and lattice corneal
      dystrophy type I. The investigation excluded this mutation in one family member
      previously classified as potentially affected. CONCLUSIONS: The investigation
      confirmed autosomal dominant inheritance with complete penetrance in the family
      described. The mutation 417C-->T has already been found earlier in another family
      of different geographic origin. These results suggest a mutation hot spot at
      position 417. In addition, no evidence of genetic heterogeneity of lattice
      corneal dystrophy type I was detected. Molecular genetic analysis (in conjunction
      with genetic counselling) therefore may be useful in routine diagnostics as the
      confirmation of the diagnosis by histological examination is possible only after
      keratoplasty. The common pathomechanism in lattice corneal dystrophy type I may
      facilitate development of new therapeutic concepts; the easy accessibility of the
      target organ may provide new possibilities e.g. for gene therapy.

PMID- 9592741
TI  - [Intracanalicular trabeculostomy--a new approach to glaucoma surgery].
AB  - BACKGROUND: A new "ab externo" technique for glaucoma trabecular surgery creating
      multiple perforations of the trabeculum to improve outflow facility was tested.
      MATERIAL AND METHOD: In order to perform a draining canal to the anterior
      chamber, a quartz fiber (phi: 300 microns) with a side-firing tip, coupled to an
      Er:YAG laser (2.94 microns), was inserted into Schlemm's canal of an enucleated
      human eye. RESULTS: Eight pulses of 8 mJ each were sufficient to perforate the
      trabecular meshwork. Histologic analysis showed a rippled canal with 50 microns
      average diameter and a surrounding necrosis zone of 15-35 microns. CONCLUSIONS:
      The Er:YAG laser trabeculostomy, in conjunction with special fibers, shows
      promise as a new "ab externo" technique for minimally invasive therapy of open
      angle glaucoma.

PMID- 9592742
TI  - [Eye injuries during a laser show].
AB  - BACKGROUND: Laser injuries are usually described in case reports concerning
      military personnel or scientists who had an accidental exposition to a laser.
      Today laser injuries to un-involved persons become more frequent. The potential
      danger for eye injuries was discussed by Birngruber and Gabel (2) in 1984.
      PATIENT: A patient presented 4 days after the accident with a monocular decline
      in vision and a scotoma after being hit by a ray of a discotheque laser. At the
      time of the accident the patient was standing on the dance floor watching a laser
      show. From that moment he reported a scotoma on the affected eye. The examination
      of the patient by an ophthalmologist 3 days later revealed a monocular decline in
      vision to 0.3 and a scotoma. Reading problems were reported. The fluorescence
      angiography confirmed the biomicroscopical barely visible line shaped defect next
      to the foveola which was according to our clinical experience caused by the ray
      of a laser. The vision defect and the scotoma remained stable during the follow
      up period. CONCLUSIONS: Before the first use of a show-laser unit it gets
      approved. Every change of the unit or the change of its position requires a new
      technical check by authorized institutions. At present many show lasers in use
      are not met with this requirement. Manipulations to the lasers are easy to
      perform and improve the intended show effect. The missing control practice
      provokes eye threatening situations for an enormous number of persons who are not
      aware of the danger.

PMID- 9592743
TI  - [Consequent use of the Aachen therapy concept after severe chemical burns of both
      eyes].
AB  - BACKGROUND: Severe chemical burn and its complications still are a serious threat
      to the afflicted eye, particularly in case of insufficient treatment.
      Rehabilitation of visual acuity can be achieved only in the minority of cases.
      PATIENT: We present a 49-year-old female patient, who suffered a severe chemical
      burn in both eyes by alcaline detergent. Visual acuity was OD 20/50, OS light
      perception. After directly started acute treatment as well as peritomy,
      peridectomy, tenon plasty and application of a PMMA contact lens a stabilization
      was achieved. Complete rehabilitation of visual acuity was gained by EDTA
      abrasion, excimer treatment, penetrating keratoplasty and cataract surgery. Last
      examination showed a visual acuity of 25/20 in both eyes. CONCLUSIONS: Even in
      severe chemical burn an optimal result can be achieved by using an adequate
      treatment conception. Immediate beginning of therapy is important as well as
      persistent and persevering application of the treatment. Repeated, if necessary
      daily, excisions of necrotic tissue associated with tenon plasty and application
      of a PMMA contact lens have special importance.

PMID- 9592744
TI  - [Indocyanine green angiography in acute posterior multifocal placoid pigment
      epithelial disease].
AB  - BACKGROUND: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is
      an idiopathic posterior segment inflammatory disorder of young adults. The
      pathogenesis remains unsettled. The placoid lesions and characteristic findings
      on fluorescein angiography have been interpreted as representing a primary
      pigment epithelial disorder or a choroidal vascular disease. PATIENT: Using
      Fluorescein and Indocyanine green angiography we examined one patient with
      APMPPE. RESULTS: In the acute phase, the fluorescein angiogram showed early
      hypofluorescence of the ophthalmoscopically visible lesions followed by late
      hyperfluorescence with centripetal staining of fluorescein at the level of the
      pigment epithelium. Indocyanine green angiograms showed in the acute stage of
      this disease areas of hypofluorescence in both the early and late pictures that
      nearly correlated with the placoid lesions. Three weeks later we saw apart from
      involution of the initial lesions, new angiographic hypofluorescent lesions at
      the posterior pole of the left eye, which were ophthalmoscopically not visible.
      During the next four weeks the older and newer lesions went smaller and left
      scars. Also the choroidal blood flow was restored partially. CONCLUSIONS:
      Indocyanine green choroidal videoangiography has shown hypofluorescence of the
      placoid lesions. This may be explained by choroidal hypoperfusion as the
      pathogenesis of acute posterior multifocal placoid pigment epitheliopathy.

PMID- 9592745
TI  - [Alagille syndrome (arteriohepatic dysplasia): stable ocular findings after 23
      years of illness].
AB  - BACKGROUND: Alagille syndrome is a arteriohepatic dysplasia which is in most
      cases correlated with ocular disorders. The most common ocular defect is a
      posterior embryontoxon. PATIENT: We report on a 27-year-old patient suffering
      from Alagille syndrome, seen in our department for 23 years. Within these 23
      years the ophthalmological status concerning visual acuity and intraocular
      pressure of the patients was stable. Iris-stroma-atrophy showed a small increase
      on both eyes. CONCLUSION: In comparison to patients with Axenfeld anomaly a
      development of glaucoma is not observed in these patients. Maybe the anomalies of
      the anterior chamber angle are less severe or different from those in Axenfeld
      anomaly. The disease is also correlated with hepato- or/and splenomegaly by
      biliary hypoplasia, cardiac disorders etc. Cooperation of paediatricians,
      internal specialists and ophthalmologists are necessary for the treatment of
      these patients.

PMID- 9592746
TI  - [Subepidermal calcified nodule (calculus) of the eyelid].
AB  - A 9-year-old boy presented with a painless hard tumor in the right lower lid. It
      had grown slowly since 12 months. Three months before presentation cryotherapy
      was administered by a dermatologist because of a presumed wart. Both eyes were
      normal. Clinical differential diagnosis included a keratoakanthoma and a wart.
      Excisional biopsy was performed. Histology revealed granular deposits which
      stained positive with hematoxylin-eosin and von Kossa stain. Though a secondary
      (dystrophic) calcinosis of the lid following cryotherapy could not be ruled out a
      diagnosis of an idiopathic subepidermal calcified nodule (calculus) of the lid
      was established.

PMID- 9592747
TI  - [Orbital sarcoidosis--a case with an unusual course].
AB  - BACKGROUND: Most cases of orbital sarcoidosis are associated with a systemic
      sarcoidosis. PATIENTS AND METHODS: A 67-year-old woman suffered from an orbital
      mass on the right side, which led to disturbance of the ocular motility. Slight
      improvement was achieved by the administration of systemic steroids. RESULTS:
      Histologically a chronic granulomatous inflammation was revealed in the biopsy of
      the orbital mass. The suspected diagnosis was sarcoidosis, but three conventional
      chest X-rays within 10 months and the serum angiotensin-converting-enzyme were
      normal. Suprisingly a computertomography of the chest showed mediastinal
      lymphomas. CONCLUSION: Granulomatous orbital inflammation without any local cause
      or other systemic granulomatous disease strongly suggests a systemic sarcoidosis.
      In case of missing lymph node enlargement in conventional chest X-ray
      computertomography should be performed.

PMID- 9592748
TI  - [Chalcosis oculi].
AB  - PURPOSE: To report on a patient including measurements of retinal changes in
      ocular chalcosis. PATIENT AND METHODS: After having suffered an open-globe injury
      presumably due to a small foreign body after a grenade explosion, a 30-year-old
      man presented six years later with ocular chalcosis including sunflower cataract,
      a multitude of tiny brownish particles in the anterior vitreous, a fibrillar
      degeneration of the posterior vitreous and brilliant patches overriding the
      foveal region. The patches were measured by confocal scanning laser tomography
      (HRT) and optical coherence tomography (OCT). RESULTS: Besides an acquired
      cyandyschromatopsia, psychophysical and electrophysiologic tests were
      unremarkable. Vision was 20/20. The central patches measured 200 to 700 microns
      in diameter (HRT) and 150 to 200 microns in height above the inner retinal
      surface (HRT and OCT). DISCUSSION: With exception of a Kayser-Fleischer ring of
      the cornea the patient presents all morphologic signs of ocular chalcosis.
      Although the observed patches on the central retina in ocular chalcosis are
      described in the literature, their nature is not known.

PMID- 9592749
TI  - [Objective criteria for expert assessment of vestibular vertigo].
AB  - BACKGROUND: Even for experienced examiners quantitative and objective medicolegal
      assessment of vestibular vertigo is difficult. Current medicolegal opinions place
      disproportionate emphasis of subjective symptoms. METHODS: Based on parameters
      from spontaneous and provoked vestibular nystagmus with Frenzel's glasses,
      objective criterias for adequate medicolegal assessment of vestibular disorders
      are presented. Diagrams in tabular form for unilateral and bilateral vestibular
      dysfunction and benign peripheral positional vertigo allow assessment of
      reduction in earning capacity. CONCLUSIONS: The widespread use of subjective
      criteria in the medicolegal evaluation of vestibular complaints should not be
      accepted. The qualified ENT specialist is able to evaluate vestibular deficits
      using objective and reproducible methods.

PMID- 9592751
TI  - [Occupational medicine aspects of nasal diseases].
AB  - BACKGROUND: With respect to occupational and environmental exposure risks and
      corresponding diseases, upper and lower airways show similarities and common
      aspects, e.g., in allergic reactions to inhalant allergens as well as in
      disorders caused by chemical irritants, toxic or cancerogenic substances. In
      addition to special occupational medical preventive examinations, an
      otolaryngologist is involved in the diagnosis, assessment, and therapy of
      occupational ENT diseases. RESULTS AND CONCLUSIONS: A significant proportion of
      ENT illnesses is work-related or represents an occupational disease. Factual
      figures are presented. A detailed occupational history of ENT patients should be
      prepared. If required, the factory physician or the expert in occupational
      medicine should be contacted to assist in appropriate preventive measures. In
      case of a confirmed diagnosis, the disease has to be reported.

PMID- 9592750
TI  - [Effect of stimulus rise time and high-pass masking on early auditory evoked
      potentials].
AB  - BACKGROUND: Problems of frequency-specific objective assessment of hearing
      threshold by means of auditory brainstem response (ABR) have been discussed
      recently. While a number of workers have recommended methods of selective masking
      to improve the frequency specificity, others believe that frequency-specific
      potentials can also be obtained without masking. In this context, the effects of
      rise-decay time and high-pass masking on ABRs were investigated. METHOD: ABRs
      were recorded in normal-hearing subjects and patients with high and low frequency
      hearing loss by means of surface electrodes between the vertex and the
      ipsilateral mastoid. The frequency of the stimulus was 1 kHz, and the rise-decay
      time 1 ms (1-0-1) or 2 ms (2-0-2). High-pass filtered noise (cutoff frequency 1.5
      kHz; filter slope 250 dB/octave) was employed for masking. Particular attention
      was paid to the problem of efficient masking. RESULTS: In normal-hearing subjects
      under the influence of high-pass masking compared to non-masked ABRs, longer mean
      latencies and diminished means of the amplitudes of wave V were found, with
      differences in the near-threshold domain being less pronounced. Similar results
      were observed in patients with high frequency hearing loss. In patients with low
      frequency hearing loss, the influence of high-pass masking was especially marked
      distinctly near to threshold. Furthermore, latency and amplitude differences of
      wave V of the 1-0-1 and the 2-0-2 stimuli were determined from the ABRs obtained
      with and without high-pass masking. The differences between the latency
      differences of both stimuli in the suprathreshold range (70 dB nHL) only were
      statistically significant. CONCLUSIONS: The results are suggestive of an
      inadequate frequency specificity of unmasked stimuli in the suprathreshold range.
      Evaluation of the latencies revealed for both rise-decay times a similar
      frequency specificity near the threshold and a higher frequency specificity of
      the longer stimulus in the suprathreshold range.

PMID- 9592752
TI  - [Tolerance, subjective complaints and mucociliary clearance in rhinitis sicca
      before and after nasal irrigation with Rhinomer Force 1].
AB  - BACKGROUND: Rhinitis sicca is a widespread disease, caused by a variety of
      factors. There are many different treatments, but none is more reliable than the
      other. METHODS: In a prospective study we examined 12 patients before and after a
      ten-day course of nasal irrigation with Rhinomer Force 1 regarding their
      symptoms, the mucociliary clearance measured with the saccharin test according to
      Andersen and tolerance of therapy. RESULTS: Improvement of nose breathing (57%),
      sensation of mucous running in the pharynx (42%), feeling of a dry nose (42%,
      significant p = 0.0313). The overall improvement was significant (67%, p =
      0.054). Mucociliary transport analysed for each side of the nose (24 sides)
      resulted in 38% improvement (up 10 min in average), 12% same result, 50%
      worsening (down 12 min in average). The acceptance was reported as very good in
      91% of the study group. CONCLUSIONS: Depending on the symptoms, a high to
      significant amount of improvement is documented after therapy with isotonic salt
      water solution. In our study the measurement of the mucociliary transport does
      not correlate with subjective symptoms. It does not appear to be an adequate tool
      for diagnosing rhinitis sicca or evaluating the success of treatment.

PMID- 9592753
TI  - [Effect of gene polymorphism on detoxifying glutathione-S-transferase enzymes on
      chromosomal stability of squamous epithelial carcinomas in the area of the head
      neck].
AB  - BACKGROUND: While cigarette smoking and chronic alcohol consumption are the major
      risk factors for the development of head and neck cancer, it is assumed that
      genetic factors contribute to risk. MATERIAL AND METHODS: We examined genotype
      frequencies from leukocyte DNA of 269 laryngeal cancer patients, 123 pharyngeal
      cancer patients and 216 controls. Polymorphisms at different glutathione-S
      transferase (GST) gene loci were investigated. Losses of heterozygosity (LOH) at
      12 different chromosomal gene loci were determined in 37 of the study patients by
      comparing blood and tumor cell DNA. The relationship between high risk genotypes
      and the occurrence of LOH was investigated. RESULTS: Glutathione-S-transferase
      high risk genotypes were identified at the first and third genes of the M family
      (GSTM1, GSTM3) and the first gene of the P family (GSTP1). These high risk
      genotypes are seen to have a statistically significant influence on the
      occurrence of LOH in the tumor tissue. CONCLUSION: There is evidence that the
      polymorphisms studied play a role in the carcinogenic process by influencing the
      chromosomal fragility which may lead to the inactivation of tumor suppressor
      genes or the activation of oncogenes.

PMID- 9592754
TI  - [Indications and risks of manual lymph drainage in head-neck tumors].
AB  - BACKGROUND: Secondary lymphedema of the head and neck can develop as a result of
      obstruction of lymphatic channels following the surgical removal of lymph nodes
      and fibrosis due to irradiation. This can be treated with manual lymphatic
      drainage. An increase of tumor recurrence due to this therapy is at controversial
      discussion. PATIENTS: In a retrospective study 191 patients treated for head and
      neck cancer were questioned on occurrence of lymphedema and therapy with manual
      lymphatic drainage. RESULTS: 100 patients had received lymphatic drainage,
      whereas 91 patients belonged to the group without lymphatic drainage therapy. In
      37 cases a tumor recurrence or local metastases were reported, 18 of whom had
      received lymphatic drainage and 19 belonged to the control group. Among these 37
      patients neither the group with lymphatic drainage nor the control group differed
      significantly concerning stage of cancer, histopathological grading, the in
      sano/non in sano resection of the primary tumor and a lymphangiosis
      carcinomatosa. An increased recurrence rate among patients who underwent a
      lymphatic drainage therapy could not be found. CONCLUSION: A lymphatic drainage
      therapy for patients presenting with lymphedema after the oncological therapy
      does not increase the rate of local recurrencies. Moreover it improves the
      quality of life after the cancer therapy. As only few data are available for
      cases with non in sano surgery and tumors with lymphangiosis carcinomatosa these
      cases should be excluded from a lymphatic drainage therapy. A spreading of occult
      tumor cells in these patients might be possible.

PMID- 9592755
TI  - [Modified posterior Dennis and Kashima cordectomy in treatment of bilateral
      recurrent nerve paralysis].
AB  - BACKGROUND: A number of different surgical methods are described in the
      literature to enlarge the glottic gap in patients with bilateral recurrent nerve
      paralysis with an excessively small glottic gap. The latest method is the
      posterior chordectomy described by Dennis and Kashima. PATIENTS AND METHODS:
      Twenty-three patients with bilateral recurrent nerve paralysis were treated
      between 1993 and 1997. In the first 5 patients, a muscular triangle as described
      by Dennis and Kashima from the posterior part of the muscular portion of the
      vocal fold was resected. Later on, the surgical procedure was extended by
      additional resection of muscular tissue from the anterior two-thirds of the vocal
      fold. Preoperative and postoperative data were carefully assessed in a
      prospective setting. Subjective data such as limitation of physical exertion and
      ability to communicate were documented. There was objective documentation by
      spirometry and phoniatric-logopedic assessment of voice quality parameters.
      Generally, it takes a number of months until the final permanent state is
      reached. The minimum follow-up was therefore at least 6 months with a mean of 16
      months. RESULTS: The follow-up of the 23 patients showed that the surgical
      technique as originally described by Dennis and Kashima does not always improve
      breathing sufficiently in the long run. A repeat chordectomy was required in
      three out of five patients with this technique. The modified technique with
      additional muscle resection of the anterior two-thirds of the vocal fold resulted
      in the desired long-term enlargement of the glottic gap in 16 out of 18 patients.
      Spirometric controls showed a significant improvement of respiration. However,
      some voice quality parameters showed a significant reduction as expected. Despite
      this, the overall communication ability was described as only slightly reduced by
      the patients themselves. CONCLUSIONS: By the modified posterior laser
      chordectomy, the glottic gap is widened on a long term, though less than after an
      arytenoidectomy. The compromise between reduction of voice quality and dyspnoea
      is better than after arytenoidectomy. The preservation of the laryngeal sphincter
      is important in that it prevents the latent aspirations that are occasionally
      observed and achieves a certain adduction of the vocal folds with phonation. The
      surgical procedure is technically simple, may be repeated, and never needs a
      tracheostomy.

PMID- 9592756
TI  - [Voice quality after partial laser laryngectomy].
AB  - BACKGROUND: We conducted a prospective study to investigate voice quality after
      transoral endolaryngeal laser surgery in terms of ability to communicate
      effectively. Eighty patients with T1 or T2 glottic carcinoma were enrolled in the
      study. The main objective was to identify the influence of type and extent of
      surgery on postoperative voice parameters after endoscopic laser surgery.
      MATERIAL AND METHODS: The postoperative mechanism of phonation was assessed by
      videostroboscopy six months after surgery at the earliest. A phonetogram was
      produced and its area calculated (relative phonetogram, RP) in relation to a
      gender-specific normal phonetogram. A speech therapist (ST) and a trained
      otolaryngologist (TO) rated each voice independently for communication ability in
      a grade from 1 (poor) to 6 (near normal). RESULTS: After simple cordectomy the
      mean values were as follows: RP = 24.8%, TO = 3.26, ST = 3.33. When the anterior
      commissure was completely preserved mean results were better (RP = 34%, TO =
      3.92, ST = 3.83). Results were worse following extended cordectomy (RP = 14.7%,
      TO = 2.82, ST = 3.00) and transglottic resection (RP = 13.7%, TO = 2.30, ST =
      2.86), but similar within these two groups. The parameters RP, TO, and ST do not
      differ significantly between the group who had speech therapy after surgery (N =
      33) and the group who did not (N = 47). Voice production at glottic level yields
      better results for every parameter than supraglottic substitute phonation. The
      amount of tissue removed was less significant. CONCLUSION: We conclude that
      postoperative phonatory results correlate with the postoperative mechanism of
      phonation. There is no linear correlation with the amount of tissue removed.
      Comparing similar types of resection preservation of the anterior commissure
      plays a key role. From the data in this study there is no evidence of a
      significant benefit from speech therapy. The parameter RP is an effective and
      relatively simple parameter to complete auditive voice assessment.

PMID- 9592757
TI  - [Primary mucous membrane melanoma of the base of the tongue].
AB  - BACKGROUND: Primary mucosal melanoma of the tongue is an absolute rarity. A
      review of the literature revealed only 28 cases. PATIENT: The following report
      deals with an 87-year-old male patient who developed a primary melanoma of the
      left base of his tongue. The melanoma was excised with the CO2 laser. The patient
      refused surgical removal of the lymph nodes as well as radiation therapy.
      RESULTS: The laser resection of the melanoma led to a local control of the tumor
      at its primary site until the patient died from a stroke 30 months after the
      initial diagnosis. CONCLUSION: Limited melanoma of the mucosa of the tongue can
      be excised with the CO2 laser, if the resection can be performed with margins of
      healthy tissue as large as those in conventional surgery. Surgical therapy with
      primary palliative intention seems also to be adequate as relief of local
      symptoms can be achieved even for a longer period of time.

PMID- 9592758
TI  - [Surgical ENT therapy of oropharyngeal amyloidosis].
AB  - BACKGROUND: The term "amyloidosis" refers to a disturbance of metabolism with a
      pathological deposit of extracellular protein. There are two types of
      amyloidosis, both of which can have oropharyngeal manifestations. The amyloid
      deposits cause dysfunction of affected tissues and could result in a life
      threatening obstruction of neighbouring organs or the upper aerodigestive tract.
      CASE REPORT: The present paper reports about the symptoms, diagnosis, and
      surgical treatment of oropharyngeal amyloidosis. The possible life-threatening
      obstruction of the upper aerodigestive tract by amyloidosis is illustrated in a
      case report. CONCLUSIONS: Surgical treatment is indicated in cases of amyloid
      caused obstruction of the upper aerodigestive tract. The transoral approach
      combined with a laser surgical tissue resection is often not efficient where
      diffuse amyloid muscular deposits are present in the form of macroglossia with
      induration of the floor of the mouth. An effective surgical treatment of
      oropharyngeal amyloidosis consists of suprahyoid pharyngotomy with a partial
      tongue resection and a supplementary reduction of the induration of the floor of
      the mouth.

PMID- 9592759
TI  - [Cervical manifestation of malignant schwannoma].
AB  - BACKGROUND: Malignant schwannomas are rare malignant mesenchymal tumors often
      associated with neurofibromatosis. They occur less frequently in the head and
      neck than in other regions. PATIENT: A case history of a primary malignant
      schwannoma of the head and neck area in a 27-year-old man is reported. The tumor
      was located in the left submandibular region. The patient did not have any
      functional deficits. The tumor was totally removed. There have been no signs of
      either recurrence or metastasis within the two years following diagnosis and
      surgery. DISCUSSION: The microscopic and immunohistochemical findings are
      presented, and the importance and therapy of this very rare malignant tumor of
      the head and neck area are discussed. CONCLUSION: Malignant schwannoma in the
      head and neck region is rare. Radical resection is the treatment of choice.

PMID- 9592760
TI  - [Reliable fixation of cochlear implant electrode mountings in children and adults
      -initial experiences with a new titanium clip].
AB  - BACKGROUND: There is a reported 1% incidence of delayed migration of extrusions
      of the electrode arrays out of the cochlea. METHODS: A titanium clip to fix the
      electrode array of the MED EL Combi 40 Cochlear Implant System is described. The
      clip is designed and shaped in a double U configuration. The clip material allows
      easy adaption to the individual anatomical situation. The clip is fixed to a bony
      bridge at the incus bar and fixes the electrode in a plane parallel to the chorda
      facial angle. It is closed around the electrode similarly to a stapes piston
      around the incus. Additional tests which examined the possible risk of damaging
      the electrode carrier and clinical findings are described. RESULTS: The clip was
      used in 23 cases with a follow-up period up to 1 year. No signs for dislocation
      of the electrode were found. In one revision case the clip was covered with a
      thin mucosal layer. The electrode array showed no signs of damage. Intraoperative
      findings confirmed the experimental tests on the electrode fixation. CONCLUSION:
      The titanium clip facilitates safe and quick fixation of the electrode array and
      prevents dislocation. its flexibility and shape minimizes the risk of damage.

PMID- 9592761
TI  - [Interesting case no. 11. Giant cell granuloma of the mandibular bone].

PMID- 9592762
TI  - [Restorative interventions of the tympanum and mastoid. I].

PMID- 9592763
TI  - DNA extraction from small blood volumes and the processing of cellulose blood
      cards for use in polymerase chain reaction.
AB  - This article describes two procedures for the purification of genomic DNA from
      small blood volumes of whole blood using DNAzol BD. In the first procedure, DNA
      is isolated from 1-20 microL of whole blood using a fast and simple protocol that
      is appropriate for the simultaneous extraction of a large number of samples. The
      isolated DNA is suitable for gel electrophoresis and polymerase chain reaction
      (PCR). In the second procedure, cellulose blood cards containing approx 5 microL
      of dried blood are treated with DNAzol BD in order to retain DNA on the cellulose
      matrix while removing other cellular components. The blood card with DNA
      subsequently serves as template in PCR. The blood card processing and
      amplification procedures are performed in the same PCR tube without any
      centrifugation steps, making the combined procedures amenable for automated DNA
      preparation and amplification in a single tube.

PMID- 9592764
TI  - High sensitivity analysis of gene expression in single embryonic somites using
      coupled reverse transcription-polymerase chain reaction.
AB  - We have developed a highly sensitive and reproducible method to detect the
      expression of specific genes in small tissue samples, such as a single embryonic
      somite. The procedure, which utilizes coupled reverse transcription-polymerase
      chain reaction (RT-PCR), was developed for evaluating the sequence of gene
      expression occurring in single somites during chick embryonic development.
      Comparisons of results obtained from using combinations of various RNA isolation
      methods and reverse transcription methods demonstrate that a protocol using a
      commercially available RNA isolation reagent (Tri Reagent) followed by optimized
      PCR, successfully detects low levels of mRNAs.

PMID- 9592766
TI  - The nonradioisotopic representation of differentially expressed mRNA by a
      combination of RNA fingerprinting and differential display.
AB  - In many applications, an understanding of differentially expressed genes in
      different tissues or owing to an applied stimulus is important. However, the wide
      use of two rather similar polymerase chain reaction (PCR)-based techniques for
      the identification of differentially expressed mRNAs (RNA fingerprinting by
      arbitrarily primed PCR [RAP-PCR] and differential display [DDRT-PCR]) has shown
      that reproducibility is still a problem. By combining features of both RAP-PCR
      and DDRT-PCR, a technique has recently been developed that avoids some of the
      disadvantages, but the use of radioisotopes for band detection still limits its
      application. We have improved this technique for analyzing differentially
      expressed mRNA by resolving the amplified products on nondenaturing
      polyacrylamide gels and subsequently staining the gels with silver nitrate. Our
      modification allows the identification of differentially expressed bands with a
      very high accuracy. Therefore these bands can be very easily reamplified and
      sequenced directly. Subsequently the differential expression can be verified by
      semiquantitative RT-PCR with specific primers derived from sequence data. These
      improvements, together with nonradioactive sequencing techniques, make it
      possible to do DD analysis completely without a health hazardous owing to
      radioactivity. The nonradioisotopic differentially expressed mRNA-PCR (DEmRNA
      PCR) is a reliable and useful modification of available differential expression
      methods.

PMID- 9592765
TI  - Tightly controlled two-stage expression vectors employing the Flp/FRT-mediated
      inversion of cloned genes.
AB  - We have developed a tightly controlled, two-stage expression system. It is based
      on a single plasmid that carries the TetR repressor/Ptet promoter/Otet operator
      for the first-stage control, and the Flp recombinase/ FRT sites for the second
      stage control. The gene to be expressed (GENE) is cloned in an inverted
      orientation (with respect to the stationary promoter) into a multiple-cloning
      site (MCS) located between two convergent FRT1 and FRT2 sites. In the OFF stage,
      no inadvertent transcription can enter the 5' end of cloned GENE because of four
      rrnBT1 terminators, located just outside the FRT1-MCS-FRT2 cassette and because
      the FRT2 construct was deprived of any promoter function. When using the lacZ
      reporter, it was shown that in their OFF stage our two-stage expression plasmids
      exhibit a significantly lower basal expression than the repressed single-stage
      tetR/PtetOtet-lacZ vectors. To enter the ON stage, the tetR/PtetOtet module is
      induced by adding autoclaved chlortetracycline (cTc), leading to synthesis of the
      Flp recombinase, which in turn, inverts the FRT1-MCS-FRT2 module together with
      the cloned GENE. This results in the massive GENE expression from one (pInvMS) or
      two (pImpMS) stationary promoters.

PMID- 9592768
TI  - Freeze-drying and cryopreservation of bacteria.

PMID- 9592767
TI  - Reference cDNA library facilities available from European sources.
AB  - cDNA libraries are the cornerstone of efforts to identify the relatively small
      regions of genomes that are responsible for biological effects. Gene hunter
      seeking candidate genes, via a variety of approaches, ultimately focus on the
      cloning, sequencing, and expression of cDNAs. Assistance is now available to
      researchers in the form of genome programs, whose initial goals include assembly
      of a complete collection of expressed sequences derived from the genome of
      interest. The concept of reference sets of cDNA libraries is that the aims of
      genome programs are served most effectively by different laboratories working on
      a common set of high-quality arrayed cDNA libraries, using different experimental
      approaches, thereby reducing unnecessary duplication of effort, and maximizing
      the amount of information that one set of resources can provide.

PMID- 9592769
TI  - Epitope mapping by surface plasmon resonance in the BIAcore.
AB  - An epitope may be defined as a specific site on an antigen module characterized
      by the binding of one monoclonal antibody (MAb). Epitope mapping by surface
      plasmon resonance in the BIAcore biosensor may be performed to characterize an
      antigen or a group of specific MAbs or both. This article describes the BIAcore
      instrument and methods for such mapping. Examples include molecular interaction
      studies with simple and complex proteins, such as myoglobin and calprotectin,
      respectively.

PMID- 9592770
TI  - PIG-B: a homemade monophasic cocktail for the extraction of RNA.
AB  - An inexpensive monophasic reagent has been developed for the extraction of total
      RNA from cells or tissues. The main ingredients of the reagent are Phenol,
      Isoamyl alcohol, Guanidinium isothiocyanate, and Beta-mercaptoethanol (PIG-B).
      The quality and yield of RNA obtained by this reagent is at par with that
      obtained by TRIzol, an expensive but widely used monophasic reagent available
      commercially. The complete composition and method of preparation of PIG-B is
      provided to aid preparation of the reagent in the laboratory.

PMID- 9592771
TI  - A cost-effective plasmid purification protocol suitable for fluorescent automated
      DNA sequencing.
AB  - A cost-effective, reliable, and reproducible method has been developed to produce
      good-quality, double-stranded plasmid DNA for automated sequence analysis. The
      method incorporates modifications to a previously described plasmid-purification
      protocol used in manual sequencing. The quality of the DNA produced from the
      present protocol is suitable for automated fluorescent sequencing. Using a dye
      terminator sequencing protocol, most runs using plasmid DNA prepared using this
      protocol produced over 700 bases with greater than 99% base-calling accuracy.

PMID- 9592772
TI  - [Acute renal insufficiency: physiopathology and treatment].

PMID- 9592773
TI  - [Epidemiology and prognosis of acute renal insufficiency in 1997. Recent data].
AB  - In an unselected population, the annual incidence of acute renal failure (ARF)
      seems close to 200 patients per million inhabitants. In elderly patients, this
      incidence is five times higher than that of younger patients. Mortality is
      particularly high in intensive care units and doubles if ARF develops after
      rather than before admission. Death is mainly due to hypovolemic and septic
      shock, and to cardiovascular diseases. An increasing number of deaths is related
      to therapeutic limitation. In many cases, ARF can be prevented, e.g. by
      correcting any sodium deficit and hypovolemia before a surgical procedure, and by
      considering the true GFR of a given patient before prescribing a potentially
      nephrotoxic drug, especially in older patients. A poor previous health status,
      hospitalization prior to admission, and ARF occurring after admission are
      important predictive factors of mortality, as well as any acute organ
      dysfunction. Second generation severity scores seem to have a better performance
      than older ones. The use of continuous hemodialysis and hemofiltration is
      increasing in ARF patients, but it is not proven that mortality is thereby
      reduced. A beneficial effect of biocompatible membranes is not clearly
      demonstrated in these patients. Later, most ARF patients recover a normal, or
      nearly normal, renal function. Recovery is delayed in older patients and in those
      whose oliguric period is prolonged. Lastly, the high cost of therapy in ARF
      justifies the use of all currently preventive measures in patients at risk.

PMID- 9592774
TI  - [Role of adhesion molecules in acute ischemic renal insufficiency].

PMID- 9592775
TI  - Inflammatory cells in renal pathology.
AB  - To gain better insight in the regeneration process responsible for the functional
      and morphological recovery after acute renal failure (ARF) is one major goal in
      the field of Nephrology. Results opposing endogeneously produced polypeptide
      growth factors to be the mediators of this process accumulate. Indeed, the early
      decrease of renal epidermal growth factor (EGF) and insulin-like growth factor-1
      (IGF-1) in different experimental models of ARF has been frequently shown at both
      the mRNA and protein level, while other growth factors could not be shown to
      increase. Moreover, the inaccessability of the upregulated receptors for
      endogeneously produced growth factors, has encouraged research to seek
      alternative origins for the signals inducing renal regeneration. The accumulation
      of mononuclear leukocytes in the renal interstitium is a striking observation in
      renal failure. The existence of a regenerative potential provided by the network
      of inflammatory mononuclear leukocytes is supported by studies on tissue repair
      in different fields. This review discusses the infiltrating network of
      mononuclear leukocytes as a major participant in the regeneration process after
      acute renal failure, including the approach which can be followed to investigate
      this hypothesis.

PMID- 9592776
TI  - [Drug prevention of acute renal insufficiency].

PMID- 9592777
TI  - [Acute renal insufficiency: nutrition disorders and therapeutic consequences].
AB  - Catabolism is usually enhanced in acute renal failure (ARF). Its magnitude varies
      from one patient to another and can change significantly in the same patient from
      day to day, reflecting its clinical course. It depends on the severity of the
      ARF, the underlying process, the associated co-morbidity, and therapeutic
      approach. The detection of patients at high risk for malnutrition is extremely
      important; nutritional markers and indexes of caloric and protein requirements
      are useful to adapt renal replacement and nutritional support to ARF patients.
      Various biochemical parameters (namely, serum albumin and prealbumin),
      anthropometic measures, indirect calorimetry, urea and creatinine kinetics are
      all useful tools to evaluate metabolic status and requirements nutritional.
      Commonly, the caloric requirements are nearly 35 kcal/kg/24 h with correction
      factors applied for certain clinical situations: carbohydrates account for 50 to
      60% of those needs whereas lipids account for the rest. The total amount of fluid
      administered has to be adapted to the possible ultrafiltration achieved by
      dialysis. Daily dialysis sessions and continuous renal replacement therapy allow
      larger volumes and thus facilitate nutritional support. Protein needs frequently
      exceed 1.2 g/kg/24 h to maintain the nitrogen balance, with a calorie to protein
      ration close to 150 kcal per g of nitrogen. Sufficient amounts of vitamins and
      oligo-elements are necessary. Stimulating anabolism by exogenous mediators, such
      as androgenic hormones or growth factors (rh-IGF1, rh-GH) is an avenue that
      deserves better definition in critically ill ARF patients.

PMID- 9592778
TI  - [Hemofiltration during severe sepsis or multiorgan failure syndrome].
AB  - Continuous renal replacement therapy (CRRT) has been used in intensive care units
      particularly in patients with sepsis or multiorgan failure. In comparison to
      intermittent haemodialysis, hemofiltration techniques offers an improved
      hemodynamic tolerance, related to the absence of osmotic pressure gradient.
      Indeed, hemofiltration is based on the physical principle of convection to remove
      substances from the plasma. The removal of substances that are released during
      sepsis, acute respiratory distress syndrome or multiorgan failure may be of
      particular interest. Several human studies have demonstrated that hemofiltration
      removes various inflammatory mediators, but the clinical significance of this
      removal remains questionable. If this removal occurs predominantly by convection,
      interest in hemofiltration will focus on high volume hemofiltration in order to
      obtain maximal ultrafiltrate flows. Patients with sepsis or multiorgan failure
      require close monitoring of most vital functions. The use of a CRRT technique
      emphasizes the importance of this monitoring and adds new monitoring issues
      relative to fluid balance, anticoagulation, hypothermia or drug removal.

PMID- 9592779
TI  - [Does the biocompatibility of the hemodialysis membrane influence the prognosis
      of acute renal insufficiency?].
AB  - Several recent publications have suggested that the use of cuprophane in the
      setting of acute renal failure is associated with a higher mortality (especially
      from sepsis) and a slower recovery of renal function in the survivors in
      comparison with more biocompatible membranes. We present here a critical review
      of these publications and point to several methodological bias that might
      invalidate their conclusions. However, while waiting further information, we
      would advocate to abandon the use of cuprophane to dialyze patients with acute
      renal failure.

PMID- 9592780
TI  - Pitfalls in neuroepidemiologic research.
AB  - In neuroepidemiologic research, there are many pitfalls to trap unwary
      investigators, whether the project is a survey, a case-control study, or some
      other type of study. We briefly discuss pitfalls relating to: research
      preliminaries (e.g., failure to decide on study objectives); personnel and
      training (e.g., deficient training); data collection (e.g., ineffective
      supervision); data ownership and data sharing (disagreement about how the data
      will be used), and report preparation (e.g., failure to interpret results in the
      context of uncertainties arising from the design and implementation of the
      research). Awareness of these pitfalls will reduce the likelihood of flawed or
      ineffective neuroepidemiologic research.

PMID- 9592781
TI  - Sample size justification in phase III/IV clinical trials.
AB  - A sample size justification is often a key component in securing funding to
      conduct a clinical trial. Sample size computations typically require supplying
      values of parameters that are unknown and subject to misspecification. As an
      alternative, we advocate a power analysis approach based on a range of reasonable
      values for such parameters. We illustrate this approach in the context of a
      secondary stroke prevention trial.

PMID- 9592782
TI  - Preventable neurological diseases worldwide.
AB  - Neuropsychiatric disorders make up a large proportion of medical conditions
      causing disability and death worldwide. This paper reviews the most significant
      neurological disorders, emphasizing the preventability of most of them. The
      worldwide impact of cerebrovascular disease, protein-energy malnutrition causing
      cognitive impairment, tetanus, dementia, meningitis, and epilepsy is summarized.
      The burden of neurological dysfunction as a complication of tuberculosis,
      measles, road accidents, congenital anomalies, malaria, falls, war, violence,
      alcohol, HIV, diabetes, syphilis, and rheumatic heart disease might also be
      lessened by preventive measures. As in other health problems, major risk factors
      are poverty, poor access to health care, and social instability.

PMID- 9592783
TI  - Incidence of transient ischemic attacks in Dijon, France. A 5-year community
      based study.
AB  - The aim of this study was to determine the incidence of first-ever TIA and the
      distribution of risk factors in those patients with TIA in Dijon. We performed a
      prospective population-based study in Dijon City with 135,000 inhabitants, from
      1990 to 1994, using several case-collection sources. Over a 5-year period, we
      recorded 258 cases of first-ever TIA, giving a crude annual incidence rate of
      38.68/100,000 for men and 32.70/100,000 for women. The mean age of first-ever TIA
      was higher in women (71.75 years) than in men (70.35 years). A CT scan was
      performed in 97% of the cases and silent lacunes were discovered in 17% of cases.
      In our 5-year study in Dijon of first-ever TIA, we found incidence rates similar
      to those of previous population-based studies. Our results also support the
      hypothesis that risk factors for TIA are similar to those for stroke.

PMID- 9592784
TI  - Differentiation of acute cortical and subcortical ischemic stroke by risk factors
      and clinical examination findings.
AB  - BACKGROUND: Differentiation between acute cortical and subcortical ischemic
      stroke may be problematic when cortical stroke presents without obvious cortical
      deficits such as aphasia, neglect or hemianopia. This study explores stroke risk
      factors and clinical variables that may assist in this differentiation. METHODS:
      Records of consecutive patients with acute ischemic stroke, examined within 72 h
      of symptom onset, were reviewed. Stroke type was verified by clinical course and
      follow-up imaging. Stroke risk factors and acute examination findings were
      compared by odds ratios and positive predictive values for cortical and
      subcortical stroke. RESULTS: For 355 patients studied, 237 had cortical stroke
      and 118 had subcortical stroke. Odds ratios for cortical stroke were highest for
      atrial fibrillation by EKG (OR = 4.77, CI = 2.08-10.94), recent hospitalization
      (OR = 4.51, CI = 2.39-8.53) and nonalert mental status (OR = 4.50, CI = 2.29
      8.87). Possible cardioembolic condition, ischemic heart disease and peripheral
      vascular disease were also significant, but hypertension, age and diabetes
      mellitus were not significantly different for the stroke subtypes. Cortical
      deficits were absent in 19.4% of cortical stroke patients on initial examination.
      Predictive models were generated based on the presence or absence of cortical
      deficits and the interaction of significant risk factors with degree of motor
      deficit. CONCLUSIONS: There are clinical features that, in addition to initial
      examination, may help differentiate cortical from subcortical ischemic stroke.
      These features may be relevant to both diagnostic and therapeutic approaches to
      acute stroke.

PMID- 9592785
TI  - Null hypothesis of husband-wife concordance of Parkinson's disease in 1,000
      married couples over age 50 in Spain.
AB  - While the search for environmental neurotoxins as causal factors of Parkinson's
      disease (PD) continues, we have found no concordance in 1,000 married couples
      over age 50 in Spain. In addition, it has been possible to identify a structural
      grouping of similar chemical characteristics that is repeated in the majority of
      organic compounds that can induce parkinsonism. These compounds have a structural
      relationship with the dopamine molecule. The principal epidemiological aspects of
      PD have a preliminary rational explanation.

PMID- 9592787
TI  - Seizure disorders in preschool children in a Serbian district.
AB  - All children born in 1989 and 1990 in the district of Krusevac in Central Serbia
      (population 140,000) were followed to the end of 1995. The total number of
      children was 3,102. The cumulative incidence of febrile seizures was 25.1/1,000,
      that of single febrile seizures 3.9/1,000 and that of epilepsy (i.e. recurrent
      afebrile seizures) 6.5/1,000. The peak age-specific rate of the first febrile and
      the first afebrile seizure was in the second year of life (11.6/1,000 and
      2.9/1,000, respectively). Among 20 cases of epileptic children, the most common
      type of seizure was the generalized type--14 cases (70%), while 6 children (30%)
      suffered from partial seizures. Of these epileptic children, there were 7
      children (35%) with associated neurological abnormalities and/or mental
      retardation, including one with tuberous sclerosis. Thirteen of the total number
      of epilepsy cases were considered as having active epilepsy (i.e. still having
      had seizures and/or being on antiepileptic therapy). The calculated point
      prevalence rate was 4.2/1,000 on December 31, 1995.

PMID- 9592786
TI  - Gene-toxin interaction as a putative risk factor for Parkinson's disease with
      dementia.
AB  - We had previously examined environmental, sociodemographic and clinical variables
      as predictors for Parkinson's disease with dementia (PD + D) and found that lower
      educational attainment, greater motor impairment and advanced age at disease
      onset were more common in PD + D than in subjects with Parkinson's disease
      without dementia (PD-D). We now explore the hypothesis that genetic traits
      coupled with nongenetic factors may raise the risk of development of PD + D. The
      study cohort of 43 PD + D and 51 PD-D subjects was analyzed examining
      environmental, sociodemographic and clinical variables along with 3 candidate
      gene markers: poor debrisoquine metabolizer allele (CYP 2D6 29B+), monoamine
      oxidase B allele 1, and apolipoprotein E epsilon 4 allele. Variables were
      initially entered into a multivariate model singly. Again lower education, age at
      onset and motor impairment appeared as predictors of PD + D while other variables
      (including allele status) failed to emerge as significant individual risk factors
      for dementia. We then examined environmental and genetic variables analyzed in
      tandem to look for potential variable interactions. Subjects who had pesticide
      exposure and at least 1 copy of the CYP 2D6 29B+ allele had 83% predicted
      probability of PD + D (stepwise logistic regression model: p = 0.0491). This case
      control study provides preliminary evidence that a gene-toxin interaction may
      play an etiological role in PD + D. Further assessment of the role of these
      putative risk factors in incident dementia in PD is indicated.

PMID- 9592788
TI  - Analysis of cerebrovascular diseases by a new 3-dimensional computerised X-ray
      angiography system.
AB  - We set out to validate the concept of three-dimensional (3D) angiography. We
      evaluated the sensitivity and the quality of morphological analysis mode possible
      by an experimental system for imaging cerebrovascular disease versus standard
      digital subtraction angiography (DSA). The system, the 3D Morphometer, is a
      computerised X-ray angiography unit capable of acquiring a set of two-dimensional
      (2D) projections during a rotation and then reconstructing a 3D volume from them.
      We studied 78 patients with suspected cerebrovascular disease. 3D and 2D images
      (standard 2D DSA performed during the same procedure), were reviewed blindly to
      assess detection and display of morphological characteristics of cerebrovascular
      diseases. We found 53 aneurysms, 22 arteriovenous malformations and two venous
      angiomas. On 3D angiography we detected two aneurysms we missed on 2D
      angiography. In 47 aneurysms on which further data were obtained during surgery
      or embolisation, the 3D angiography allowed more accurate analysis of the neck
      and surrounding vessels in cases in which the 2D angiographic findings were
      doubtful. Assessment of arteriovenous malformations was equivalent with both
      techniques. Under the conditions of our study, the technical constraints being
      the same for both methods, 3D angiography was superior to 2D angiography.
      Implementation on C-arm vascular systems is being evaluated.

PMID- 9592789
TI  - Assessment of malignancy of glioma by positron emission tomography with 18F
      fluorodeoxyglucose and single photon emission computed tomography with thallium
      201 chloride.
AB  - The histological diagnosis and proliferative potential measured by
      bromodeoxyuridine (BrdU) labelling index (LI) were correlated with preoperative
      CT and contrast-enhanced, MRI, 18F-fluorodeoxyglucose positron emission
      tomography (PET) and 201T1 single photon emission computed tomography (SPECT) in
      43 patients with various grades of glioma. 201T1 SPECT had slightly higher
      sensitivity to tumours with BrdU LI > or = 5% (showing 10/10) than 18F-FDG PET
      (7/8 tumours). 18F-FDG PET was better for identifying tumours of BrdU LI < 1%
      (13/15) than 201T1 SPECT (13/22). Accumulation of 201T1 in the tumour was
      slightly different from contrast enhancement on CT and/or MRI, and gave "false
      positive" results in some low-grade gliomas. However, 201T1 SPECT, which is
      available in many hospitals and may cost less, provided useful information to
      supplement that from CT and MRI.

PMID- 9592790
TI  - Comparison of echo-planar sequences for perfusion-weighted MRI: which is best?
AB  - We compared gradient-echo (GRE), spin-echo (SE) and stimulated-echo (STE) echo
      planar imaging sequences for perfusion-weighted imaging at different field
      strengths. Focal cerebral ischaemia was induced by endovascular occlusion of the
      middle cerebral artery in eight rats. MR was performed at 4.7 T or 2.35 T. With
      each sequence, we acquired data sets before, during and after bolus injection of
      Gd-DTPA with a time resolution of 1.2 s per image. The perfusion-weighted images
      were assessed with regard to image quality, artefacts, signal-to-noise ratio
      (SNR), and signal-at-tenuation-to-noise ratio (delta SNR) of the non-ischaemic
      tissue. Visual assessment showed GRE-EPI images acquired at 4.7 T to suffer from
      distortion due to susceptibility artefacts. Artefacts were less marked with the
      SE and STE series. The GRE-EPI sequence gave the highest SNR and delta SNR. At
      2.35 T, the SNR of the STE sequences was less than 3 and therefore did not allow
      construction of reliable signal-time curves. SE-EPI was best suited for perfusion
      weighted imaging at high field strength thanks to its minimal distortion
      artefacts and high SNR. Using lower field strengths (2.35 T and less),
      susceptibility artefacts are reduced; GRE-EPI sequences are then best suited,
      because they have the highest SNR and T2* sensitivity.

PMID- 9592791
TI  - Spinocerebellar ataxia type 6: MRI of three Japanese patients.
AB  - We describe the MRI findings in three Japanese patients with spinocerebellar
      ataxia type 6 (SCA6) in which a polymorphic CAG repeat was identified in the gene
      encoding the alpha 1A voltage-dependent P/Q-type Ca2+ channel subunit (CACNL1A4).
      All showed slowly progressive cerebellar ataxia and mild pyramidal signs.
      Neuroradiologically, they had moderate cerebellar atrophy, most prominently in
      the superior vermis, whereas the brain stem appeared to be spared. No abnormal
      signal intensity was identified.

PMID- 9592792
TI  - Osmotic demyelination syndrome with a dysequilibrium syndrome: reversible MRI
      findings.
AB  - Neurological disorders may be seen in end-stage renal disease patients due to
      uraemia or to complications of dialysis. A dysequilibrium syndrome may be seen,
      usually soon after or towards the end of haemodialysis. This group of patients
      has no particular findings on MRI. On the other hand, the osmotic demyelination
      syndrome has definitive MRI findings, not to date reported with the
      dysequilibrium syndrome. We report a patient with end-stage renal disease and the
      dysequilibrium syndrome who showed findings of osmotic demyelination on MRI. The
      patient had a convulsion after a first haemodialysis, with quadriparesis and
      hyperactive deep tendon reflexes and bilateral Babinski signs. The upper motor
      neurone signs lasted for a week. Meanwhile, he was also dysarthric and had
      dysphagia. He recovered neurologically without any residuum following appropriate
      treatment and there was improvement on MRI.

PMID- 9592793
TI  - Primary paraganglioma simulating pituitary macroadenoma: a case report and review
      of the literature.
AB  - A 76-year-old woman presented with an intrasellar and suprasellar mass which
      caused deterioration of visual acuity and bitemporal visual field defects.
      Transsphenoidal and transcranial partial resection revealed a primary
      chemodectoma. This tumour is very rare in the sellar area, where there are
      normally no paraganglionic cells. We review the literature and discuss possible
      mechanisms for the development of this tumour.

PMID- 9592795
TI  - Dural arteriovenous fistula: a pitfall of time-of-flight MR venography for the
      diagnosis of sinus thrombosis.

PMID- 9592794
TI  - Primary intracranial leiomyoma: case report.
AB  - We present a case of intracranial parenchymal leiomyoma in a 20-year-old woman
      with a chief complaint of numbness and a painful sensation over the right limbs
      for several years. CT and MRI revealed an intensely enhancing calcified mass. The
      patient was well, without recurrence, 2 years after surgery.

PMID- 9592796
TI  - Giant aneurysm of the vertebral artery in neurofibromatosis type 1: report of a
      case and review of the literature.
AB  - Cranial and cervical vessels are rarely involved in neurofibromatosis type 1.
      Stenoses and occlusion due to intimal or medial dysplasia are most often seen,
      followed by aneurysms. We report a rare asymptomatic giant aneurysm of the
      vertebral artery in a 59-year old man with von Recklinghausen's neurofibromatosis
      and review the literature.

PMID- 9592797
TI  - Spontaneous healing of cervical pseudoaneurysm in vertebral artery dissection
      under anticoagulant therapy.
AB  - We report a 41-year-old woman with embolic stroke of the mid-pons attributed to
      embolism from vertebral artery dissection. Angiography revealed an occluded
      artery on one side and an incidental pseudoaneurysm of the midcervical portion of
      the vertebral artery on the other. After 3 months of warfare in therapy control
      angiography showed complete occlusion of the pseudoaneurysm. We discuss
      therapeutic choices and review the literature.

PMID- 9592798
TI  - Hypoplasia of the internal carotid artery with intercavernous anastomosis.
AB  - We report a symptomatic case of unilateral hypoplasia of the internal carotid
      artery with an intercavernous anastomosis, a very rare developmental anomaly. The
      symptoms were caused by occlusion of the proximal middle cerebral artery which
      possibly related to the haemodynamic stress caused by the anomalous
      intercavernous anastomosis.

PMID- 9592799
TI  - MRI of spinal cord involvement in Behcet's disease: case report.
AB  - MRI demonstrated well-defined areas of signal change and moderate contrast
      enhancement in the thoracic spinal cord of a patient with Behcet's disease
      presenting with subacute myelopathy. The patient improved after intravenous
      steroids, and MRI 5 months later showed a normal spinal cord.

PMID- 9592801
TI  - Synovial sarcoma of the parapharyngeal space: CT and MRI.
AB  - We present the CT and MRI findings of a histologically proven synovial sarcoma
      arising in the left parapharyngeal space of a 21-year-old man. CT was useful for
      confirming the presence of calcification within the tumour, which may be a
      favourable prognostic sign, and in excluding involvement of cortical bone. The CT
      and MRI findings were, however, nonspecific. MRI was superior to CT for assessing
      the topographical relationships of the tumour to the vessels and the invasion of
      neighbouring structures.

PMID- 9592800
TI  - Air bubbles in the subclavian or internal jugular veins: a common finding on
      contrast-enhanced CT.
AB  - We investigated the frequency of air bubbles in the subclavian (SCV) or internal
      jugular (IJV) vein in 200 patients who underwent contrast-enhanced CT of the head
      and neck. Half the patients were reviewed retrospectively (group 1), while the
      other half were investigated prospectively after the radiologists who
      administered the contrast medium were instructed to be careful not to inject even
      a single air bubble during the procedure (group 2). Air bubbles were observed in
      the SCV or IJV in 15 of the 100 patients in group 1, while in group 2, there were
      4 such patients. Air injection, a common "complication", can be reduced by care
      during the procedure.

PMID- 9592802
TI  - Schwannoma of the tip of the nose: MRI.
AB  - We report a schwannoma with a rare location at the tip of the nose in a 20-year
      old woman with an otherwise unremarkable medical history. The imaging findings
      underline the usefulness of MRI in narrowing down the differential diagnosis of
      masses in this region. Once the diagnosis was focussed on a neural origin of the
      mass, the exact nature of the tumour could not be predicted from the MRI,
      although the presence of a capsule on imaging studies as well as at operation
      suggested it was probably a schwannoma. A schwannoma must be considered when one
      encounters a sharply delineated mass at the tip of the nose, showing high signal
      on T2-weighted images and strongly contrast enhancement.

PMID- 9592803
TI  - Diffusion- and magnetisation transfer-weighted MRI in childhood moya-moya.
AB  - MRI in two children with moya-moya demonstrated low signal on T2-weighted images
      in the acute and subacute phases of ischaemia. Gradient-echo sequences, more
      sensitive to magnetic susceptibility, demonstrated these abnormalities better.
      Signal loss, due to temporary accumulation of iron, decreases progressively and
      disappears in the chronic stage of the disease. Diffusion-weighted MRI allows
      early detection of ischaemic lesions and can be used to monitor progressive
      spreading of the lesions. Magnetisation transfer maps provide sharp contrast,
      useful for demonstrating cortical atrophy.

PMID- 9592804
TI  - Percutaneous aspiration of lumbar synovial cyst: CT and MRI considerations.

PMID- 9592806
TI  - [Involvement of cytochromeP4503A4 in the metabolism of haloperidol and
      bromperidol].
AB  - To clarify the involvement of cytochromeP450 (CYP) 3A4 in the metabolism of
      haloperidol and bromperidol in humans, the effects of itraconazole, a potent
      inhibitor of CYP3A4, on steady-state plasma concentrations of both drugs and
      their reduced metabolites were investigated using 21 schizophrenic patients.
      Patients treated with haloperidol 12 or 24 mg/day (n = 13) or bromperidol 12 or
      24 mg/day (n = 8) for at least 2 weeks were then given itraconazole 200 mg/day
      for 7 days. Blood samplings were performed before administration, 1 week during
      itraconazole coadministration and 1 week after its discontinuation together with
      clinical assessments. Plasma concentrations of haloperidol and bromperidol and
      their reduced metabolites were significantly higher during itraconazole treatment
      (P < 0.01). Deterioration in the neurological side effects of haloperidol was
      observed during itraconazole coadministration. Thus, this study suggests that
      itraconazole inhibits the metabolism of haloperidol and bromperidol, and that
      CYP3A4 is involved in the metabolism of both drugs.

PMID- 9592805
TI  - Partial inhibition of reverse tolerance by a high dose of ritanserin or low dose
      of haloperidol in methamphetamine-sensitized rat.
AB  - To clarify the implication of antagonism of serotonin (5-HT)2 receptors in the
      treatment of schizophrenia, the effects of ritanserin (RIT) on the development of
      reverse tolerance in rats repeatedly administered methamphetamine (MAP) were
      investigated and compared with those of low doses of haloperidol (HPD). RIT
      administered at a dose of 2 mg/kg and low doses of HPD (0.05, 0.1 mg/kg) shared
      partial inhibition of the development of reverse tolerance in MAP-sensitized
      rats; the drugs inhibited sniffing but not head moving and had no effect on
      locomotion or rearing. A combination of low doses of HPD and RIT resulted in the
      inhibition of head moving. These results suggested that strong antagonism for 5
      HT2 receptors would be useful to some extent to treat MAP-induced psychosis and
      schizophrenia as well as weak antagonism of dopamine D2 receptors, and that a
      combination of these two actions would produce better results in these psychoses
      than that obtained from D2 antagonism alone. In the presence of 0.05 mg/kg of
      HPD, RIT caused increased locomotion and rearing, whereas it decreased them in
      the presence of 0.1 mg/kg of HPD. This result suggested that the interactions
      between 5-HT and dopamine (DA) neurons are complex, and that 5-HT2 antagonism may
      inhibit or disinhibit DA neurons depending on the level of D2 blockade.

PMID- 9592807
TI  - [Suppression of conditioned fear by administration of CCKB receptor antagonist
      PD135158].
AB  - The aim of this study is to determine whether or not CCKB receptor antagonist
      PD135158 suppresses conditioned fear. Rats were individually subjected to 30 min
      of inescapable electric footshock in a chamber with a grid floor. PD135158 or the
      vehicle was administered 30 min before placing the rats in the shock chamber
      again. The rats were observed for 5 min without receiving shock. The
      administration of PD135158 30 min before conditioned-fear stress significantly
      reduced freezing behavior. PD135158 blocked the expression of conditioned fear.
      PD135158 was again administered 30 min before footshock. Then, the rats were
      individually subjected to 30 min of inescapable electric footshock in the shock
      chamber. Twenty-four hours after receiving footshock, the rats were again placed
      in the shock chamber and observed for 5 min without shock administration. The
      administration of PD135158 30 min before footshock significantly reduced
      conditioned freezing. PD135158 blocked the anxiety of conditioned fear. PD135158
      blocked not only the anxiety, but also the expression of conditioned fear. These
      results suggest that CCKB receptor might play an important role in conditioned
      fear stress. They indicate that CCKB receptor is related to anxiety.

PMID- 9592808
TI  - Effects of washing procedure on platelets pretreated with serotonin uptake
      inhibitors in vitro: low Ki values predict long-lasting inhibition of serotonin
      uptake in vivo.
AB  - The effect of a washing procedure on serotonin (5-HT) uptake in vitro was
      investigated using human platelets pretreated with nine 5-HT uptake inhibitors
      and various Ki values to confirm the assumption that a drug with high affinity
      for the 5-HT uptake site would be hardly removed and have a long-lasting effect
      in vivo. Among the drugs tested, those with low Ki values, such as clomipramine,
      duloxetine and paroxetine, inhibited 5-HT uptake even after removal from the
      medium, while those with high Ki values such as amitriptyline, desipramine,
      imipramine, mianserin, trazodone, and zimelidine were easily removed by washing.
      The results indicated that low Ki values might be proportionally related to the
      long-lasting binding of drugs to the 5-HT uptake site. The results also suggested
      that the threshold Ki value which could separate 5-HT uptake inhibitors with a
      probable long-lasting effect in vivo from those without the effect would be
      between 5 nM and 42 nM.

PMID- 9592809
TI  - Differential effects of chronic administration of the antidepressants
      amitriptyline and rolipram on adenylyl cyclase activity.
AB  - Significant increases were observed in guanylylimidodiphosphate- and fluoride
      stimulated adenylyl cyclase activities in synaptic membrane preparations from rat
      cerebral cortex subsequent to the repeated administration of rolipram and
      amitriptyline. The potency of GppNHp-dependent inhibition of adenylyl cyclase was
      decreased by chronic treatment with rolipram but not by amitriptyline treatment.
      These findings suggest that chronically administered rolipram and amitriptyline
      share the augmentation of adenylyl cyclase activity by different actions on post
      receptor signaling.

PMID- 9592810
TI  - [Neurosurgery and molecular biology: (series 2). Molecular biology of glial
      cells].

PMID- 9592811
TI  - [Anatomical and surgical note: anterior transpetrosal approach].

PMID- 9592812
TI  - [Spinal cord stimulation therapy at an early stage for unresponsive patients with
      hypoxic encephalopathy].
AB  - Recently, spinal cord stimulation (SCS) has been used for the treatment of
      patients in prolonged coma. However, the results of SCS in unresponsive patients
      with hypoxic encephalopathy at the chronic stage have not been satisfactory.
      Considering these circumstances, we began SCS from one month after the onset of
      hypoxic encephalopathy and evaluated its effect. Twelve patients (5 males and 7
      females) with hypoxic encephalopathy, ranging in age from 7 to 72 years, were
      treated with SCS. The causes of hypoxia were acute cardiac failure in 4,
      automobile exhaust gas poisoning in 2, and asthma, pneumothorax, anaphylaxis,
      asphyxia, drowning and hypotension during aortic surgery in one patient each. One
      month after the onset, an electrode for electrical stimulation was implanted in
      the epidural space at the C2-C4 level under general anesthesia. The spinal cord
      was stimulated for 8 hours each day, starting on the day after implantation, and
      was continued for 3 months. Magnetic resonance imaging (MRI), cerebral blood flow
      (CBF) measurement using xenon-computed tomography (Xe-CT), and measurement of
      auditory evoked potential (AEP) and somatosensory evoked potential (SEP) were
      carried out 3 weeks after the onset for presurgical evaluation. Among the 12
      patients, 7 (58%) showed clinical improvement, beginning within two weeks after
      starting stimulation. They were able to communicate with others and to express
      their emotion. However, disturbance of writing, picture drawing and calculation
      were not improved by stimulation. From presurgical evaluation, cases in which SCS
      therapy was effective had the following features: 1) No hemorrhagic infarction in
      the basal ganglia was demonstrable by MRI. 2) Mean hemispheric CBF measured by
      the Xe-CT method exceeded 25 ml/100 g per min. 3) The mean increase in
      hemispheric CBF 20 min after acetazolamide administration exceeded 5 ml/100 g per
      min. 4) An N20 peak was evident on the median nerve SEP, SCS appears to be an
      effective supplementary for unresponsive patients with hypoxic encephalopathy at
      the subacute stage, in addition to rehabilitation and drug therapy.

PMID- 9592813
TI  - [Predictability of EC/IC bypass function: a retrospective study].
AB  - Although the efficacy of extracranial/intracranial bypass for reduction of risk
      of ischemic stroke has been denied, we have encountered patients in whom bypass
      operation seems to have improved his or her clinical course. The efficacy of
      bypass should be evaluated not by the patency of the bypass but by the extent of
      collateral circulation brought about by the bypass. We retrospectively analyzed
      our patients to determine whether the extent of bypass flow could be predicted
      from the results of preoperative studies. In 18 hemispheres of 18 consecutive
      patients who underwent extracranial/intracranial bypass surgery, correlation
      between the extent of bypass flow and the multiple preoperative factors including
      the angiographic findings were investigated. The bypass function was highly
      predictable in the light of preoperative studies. In all of 10 hemispheres in
      patients under 70 years of age and with occlusive lesions in the proximal portion
      of the middle cerebral artery, collateral circulation through the bypass
      developed to an extensive or a moderate degree. In 9 of 10 hemispheres in which
      an interval between the latest attack and the diagnosis of hemodynamic failure
      was 4 weeks or longer, collateral circulation through the bypass was shown to
      have developed to an extensive or a moderate degree. Our results indicate that
      extensive or moderate collateral circulation through the bypass can be expected
      only in patients under 70 years of age, with lesions in the proximal portion of
      the middle cerebral artery, and in whom an interval between the latest attack and
      diagnosis of hemodynamic failure was 4 weeks or more.

PMID- 9592814
TI  - [Perioperative management of intracranial hemorrhage related to hematological
      disease].
AB  - Six patients with hematological disease complicated by intracranial hemorrhage
      were surgically treated in the last 2 years. In this study, in order to clarify
      indication for operation and perioperative management, 6 cases were classified
      into 2 groups. The details of each group were as follows: Group 1 was defined by
      the fact that the underlying hematological disease had not yet been controlled.
      (One case was ITP and the others were 2 AML cases). Group 2 was defined by the
      fact that the underlying hematological disease was well controlled. (One case was
      CML, one case was ATL and one case was ITP). A tendency to bleed was corrected in
      all patients of group 1 in the perioperative period. In the AML cases, prevention
      of infection was mandatory because both AML cases had been in remission, and no
      serious postoperative complication had occurred. The outcome of short term
      treatment was excellent in all but one case, in whom the recurrence of subdural
      hematoma caused death during the period 1 month after operation. On the other
      hand, no cases classified in group 2 needed specific hematological perioperative
      management and the short term treatment outcome was excellent. Since intracranial
      hemorrhage related to hematological disease has often been fatal, those patients
      were treated conservatively in most cases. However, from our analyses, we were
      able to emphasize that most intracranial hemorrhage related to hematological
      disease might be treated surgically and with good result, if the underlying
      hematological disease has entered the remission period.

PMID- 9592815
TI  - [Superselective angiographic findings of ipsilateral middle meningeal artery of
      chronic subdural hematoma in adults].
AB  - The authors reported the results of continuous superselective angiography of the
      ipsilateral middle meningeal artery (MMA) in cases of chronic subdural hematoma
      (CSH) in adults. MMA angiography was performed twice, at an interval of
      approximately two weeks, in 3 cases of conservative and 1 case of surgical
      treatment. The features of MMA angiographic findings were diffuse dilatation of
      MMA and visualization of scattered abnormal vascular networks (VN), which seemed
      to be macrocapillaries in the outer membrane of the CSH. In two out of the three
      cases of conservative treatment, these VN revealed a dynamic change temporarily
      and spatially, i.e. either enlargement or reduction. In one case with a long
      clinical course a stable MMA angiogram was seen. The operated case showed
      dramatic change on the second (postoperative) MMA angiogram. The VN around burr
      hole portion was huge and dark, and several newly visualized small arteries
      penetrated the enlarged VN, which was thought to have been caused by the
      operation. The mean blood pressure in the MMA was 103 mmHg. The reason for the
      acute enlargement of the CSH might be explained as arterial bleeding into the
      hematoma cavity, caused by rupture of thin walled macrocapillaries by direct
      arterial pressure.

PMID- 9592816
TI  - [The management of slit-like ventricle with the Medos programmable Hakim valve
      and the ventriculofiberscope].
AB  - A slit-like ventricle is one of the serious complications which can occur after a
      shunting operation. Low pressure valve systems are usually applied for
      hydrocephalus during infancy. As a result the shape of the ventricle often
      becomes slit-like after the operation. Many shunt dependent children with slit
      like ventricles have to undergo shunt revisions repeatedly. From April 1995 to
      February 1997 the authors used the Medos programmable Hakim valve system for 20
      hydrocephalic children with slit-like ventricles who had been suffering from
      multiple shunt problems. The patients ages at the operation were between 3-16
      Male:Female was 12:8. Follow up periods were 10-20 months. In 12 of 20 patients
      the shunt revisions were performed at the time of shunt dysfunction and the valve
      pressure levels were able to be set at the highest levels without the appearance
      of any symptoms. In this group the size of all the ventricles had become slightly
      enlarged. In the other 8 patients the operations were performed for fear of other
      troubles arising if shunt revisions were neglected. In this group the valve
      pressure levels were set with reference to the intraoperative ICP. It took a
      relatively long period to elevate the valve levels. Shunt dysfunction due to
      obstruction of the ventricular catheter was seen in one case but the symptom was
      not so severe and the catheter which had firmly adhered to the choroid plexus was
      removed endoscopically. In 2 cases of this series the shunt systems were
      successfully eliminated. The authors report the method and efficacy of their
      series using the Medos programmable Hakim valve system and a newly developed
      ventriculofiberscope for the slit-like ventricle of children.

PMID- 9592817
TI  - [Multiple bacterial aneurysms: case report].
AB  - A 59-year-old man presented with an internal carotid artery (ICA) bacterial
      aneurysm which ruptured during surgery for treatment of another bacterial
      aneurysm. He had been admitted to our hospital because of the recurrence of colon
      cancer. He had undergone aortic and mitral valve replacement because of closure
      incompetence due to bacterial endocarditis two months previously. Two months
      after treatment for colon cancer, he developed fever, and arterial blood culture
      demonstrated. Staphylococcus epidermidis. A few days later, he suddenly suffered
      severe headache and vomiting, followed by deterioration of consciousness. CT
      showed subarachnoid hemorrhage and angiography showed a saccular aneurysm at the
      opercular portion of the left middle cerebral artery (MCA). Immediate clipping of
      the aneurysm was attempted. The carotid cistern was opened via a left
      frontotemporal craniotomy, but an ICA aneurysm, which had not been previously
      recognized, ruptured suddenly. The ICA aneurysm was wrapped with Vascwrap with
      some difficulty. The MCA aneurysm was then trapped. Postoperatively, the patient
      continued to be stuporous for a few days. Two weeks later, he died of
      complications caused by pneumonia. Bacterial aneurysm is more likely to be
      located in the distribution of the distal arterial tree, mainly in the
      distribution of the MCA. The difficulty of preoperative diagnosis and the
      unpredictable clinical course of bacterial aneurysms are emphasized.

PMID- 9592818
TI  - [A huge retrocerebellar arachnoid cyst with syringomyelia: case report].
AB  - The authors report a case of a huge posterior fossa arachnoid cyst with
      syringomyelia. This 22-year-old man presented with a history of drop attacks.
      Magnetic resonance imaging demonstrated ventricular hydrocephalus, a huge
      posterior fossa arachnoid cyst and syringomyelia. Cyst-peritoneal shunting was
      installed. The patient had an uneventful postoperative course, and his drop
      attacks disappeared. Magnetic resonance imaging one month after surgery showed
      reduction of the ventricular size and size of the arachnoid cyst and syrinx.
      Large arachnoid cysts in the posterior fossa are reported occasionally, but rare
      with syrinx. The authors described this case to illustrate the possible
      contribution of the pathogenesis of the syringomyelia associated with a huge
      posterior fossa arachnoid cyst.

PMID- 9592819
TI  - [Introduction and comments on the NINDS clinical criteria for the diagnosis of
      progressive supranuclear palsy].

PMID- 9592820
TI  - [Mental retardation and fragile X syndrome].

PMID- 9592821
TI  - [An abnormality of facial nerve conduction velocity distribution (FNCVD) in
      Bell's palsy patients].
AB  - We studied bilateral facial nerve conduction velocity distribution (FNCVD) of 8
      Bell's palsy patients in their paretic and recovered state and unilateral FNCVD
      of 13 normal control using collision method. Dual supramaximal stimuli were
      adapted to marginalis mandibulae branch of facial nerve and compound muscle
      action potential (CMAP) was recorded from the surface of mentalis muscles. Peak
      of FNCVD in normal control was present at 22-23 m/sec. In Bell's palsy patients,
      there was no significant change in FNCVD either at paretic or recovery state.
      Peak of involved side FNCVD of Bell's palsy patient was almost normal but its
      amplitude was low. However, in healthy side of Bell's palsy patient, peak of
      FNCVD was present at 18-19 m/sec. This finding shows that facial nerve diameter
      distribution in the healthy side of Bell's palsy patient has smaller peak than
      that of normal control.

PMID- 9592822
TI  - [Neural protective agents, propentofylline (PPF) could induce apoptotic cell
      death in the human glioma cells: analysis of Bcl-2 and Bax alpha/Bax beta
      expressions].
AB  - In the previous study, we have shown that propentofylline (PPF) could induce the
      cellular differentiation and apoptosis-related growth regression in the human
      glioma cell lines. Its biological functions were partly due to the increasing
      endogeneous NGF and its high affinity receptor, trk A productions. Although
      little has been known about the precise machinary regulating the propentofylline
      induced apoptosis. Recently, we have found that propentofylline could modulate
      some apoptosis related genes products in the glioma cell lines, i.e. NGF, trk A
      mRNA levels and Fas protein expressions were increased, whereas bcl-2 mRNA level
      was decreased. In the present study, we examined the apoptotic signal cascade,
      especially focusing on the expressing pattern of Bcl-2/Bax gene products. In the
      normal human astrocyte cells, Bax-beta was markedly expressed, whereas Bcl-2 and
      Bax-alpha proteins and mRNA were weakly or even nondetectable. Accordingly, Bax
      beta might be a dominant variant in the normal glial cells, which could have the
      appropriate balance of proapoptotic (Bax beta) and anti-apoptotic proteins (Bcl
      2). In the glioma cells, we showed the over-expressions of Bcl-2 and Bax alpha
      compared with the normal counterparts. According to Bax dominant theory, Bax, not
      Bcl-2 may have a major role in regulating apoptosis by means of homodimerization.
      In might be implied that in the glioma cells, excessive expressions of Bcl-2 and
      Bax alpha would favor the formation of the Bax alpha/Bax beta heterodimer or the
      Bax beta/Bcl-2 heterodimer rather than the Bax beta/Bax beta homodimer, which
      might be presumed to be functional proteins. And finally the increasing relative
      ratio of Bax alpha/ Bax beta or Bax beta/Bcl-2 to Bax beta/Bax beta could allow
      the tumor cells to survive. Thus over-expression of the bcl-2 and bax alpha gene
      renders the glioma cells resistant to apoptosis. In the present study, PPF could
      promote Bax beta over-expression and Bcl-2 retardative expression in the glioma
      cells, whereas had no effect on Bax alpha expression. Therefore, PPF might
      promote apoptotic cell death through the mechanism that restore the glioma cells
      to the appropriate balance of proapoptotic and anti-apoptotic proteins like as
      normal astrocytes. Our results indicated that propentofylline might have a
      potential role as apoptotic modulators in the human glioma cell lines, not only
      its protective activities against neuronal ischemic damages.

PMID- 9592824
TI  - [Direct continuous observation of in situ thrombolysis in the cerebral embolic
      model of rabbits].
AB  - To investigate the occurrence of cerebral embolism, a rabbit embolic stroke model
      was used for the continuous monitoring of the change of the thrombus. Red
      thrombus was directly injected into the internal carotid artery via the catheter
      inserted into the external carotid artery. The migration of the thrombus into the
      middle cerebral artery was judged as the completion of an embolism. The change of
      the thrombus and its movement was observed for a period of two hours. The
      experimental group received recombinant tissue plasminogen activator (TPA) for
      the thrombolysis while the control group received a saline solution for 30
      minutes. The thrombus in the middle cerebral artery was continuously observed for
      two and a half hours. 1. There was a spontaneous movement of the thrombus during
      the first two hours in six out of 18 cases. One case showed a spontaneous
      regression in size at the migration site. 2. White thrombus formation occurred
      around the thrombus in eight out of 18 cases. 3. In the TPA injected group,
      thrombolysis was observed in nine out of ten rabbits. The accompanied white
      thrombus was also found to be degraded. However, after the TPA injection, white
      thrombus was newly formed during the lysis of red thrombus. 4. In the saline
      solution injected control group, only partial recanalization occurred in three
      out of eight rabbits. There was no white thrombus formation in the control group.
      5. There was no significant difference in the degree of Evans blue exudation
      between these two groups. Secondary activation of the platelet function easily
      occurred by the change of the blood flow during thrombus migration and also
      thrombolysis. In conclusion, thrombolysis therapy may be more effective when TPA
      is administered in conjunction with the suppression of platelet function.

PMID- 9592825
TI  - [The role of the right hemisphere on recovery from Wernicke's aphasia].
AB  - We report a rare case of severe Wernicke's aphasia who showed a rapid and
      surprisingly good recovery despite of a large infarct involving the left
      posterior language area. A 68-year-old right-handed woman without a family
      history of left-handedness developed a severe comprehension difficulty and
      paraphasic output following a large infarct in the left posterior temporoparietal
      region. However, in 6 weeks, naming, comprehension, and repetition of words
      became almost normal. Spontaneous speech also became almost normal, although
      comprehension and repetition of sentences remained slightly impaired. The lesion
      size remained unchanged. A dichotic listening test 4 months after the onset
      showed clear left ear superiority. We speculate from these observations that the
      dormant language function in the right hemisphere might have played a role for
      rapid and good recovery of this case.

PMID- 9592823
TI  - [Developmental plasticity of corticospinal projections in the spinal cord gray
      matter of normal and hemicortectomized rat].
AB  - In the previous study we demonstrated in rats that aberrant ipsilateral CST
      fibers were increased when the cerebral cortex was surgically ablated
      unilaterally during the neonatal period. Origin of these aberrant fibers was
      confirmed to involve collateral axons, ramified from their parent axons. In this
      study, possible plastic change and the critical period for the outgrowth of CST
      fibers into the spinal cord gray matter in the rat after unilateral (right side)
      cortical damage at different ages measured in days were examined using
      anterograde horseradish peroxidase (HRP). HRP was injected into the left
      sensorimotor cortex in both normal and experimental rats. In the normal control
      rats, the outgrowth of HRP positive axons into the spinal gray matter was first
      noticed at 7 day of age in the vicinity of the right dorsal funiculus, and then
      reached maximal density and extension at 10 and 14 days of age, respectively.
      From 21 days onwards, the density and extension of HRP positive axons in the gray
      matter decreased rapidly except in the medial part close to the dorsal funiculus.
      In rats whose right cerebral cortex were damaged at day 1 of age, the pattern of
      the outgrowth of HRP positive axons into the right gray matter was much the same
      as that in age-matched controls. However, significantly different from the
      control, many HRP positive axons were noted even in the contralateral gray
      matter. HRP-positive axons in the contralateral left gray matter were also
      abundant in the rats who sustained cortical damage at 7 and 14 days, but were
      decreased considerably when the cerebral cortex was damaged at 28 days of age.
      When damage occurred at 56 days of age, HRP-positive axons did not increase in
      the left gray matter, indicating that the critical period of axonal plasticity
      after localized damage was before 4 weeks of age in rats.

PMID- 9592826
TI  - [Superficial siderosis of the central nervous system: an electrophysiological
      study].
AB  - Superficial siderosis of the central nervous system (SS) is a rare neurological
      disorder characterized by symptoms such as neurosensory hearing loss, ataxic
      gait, and spastic paraparesis. Recently, magnetic resonance imaging (MRI) enables
      us to make a clinical diagnosis. However, the exact pathophysiological mechanism
      underlying this disorder remains uncertain. Although iron chelation therapy has
      been attempted experimentally, it has not been successful and there is no
      effective medical treatment available. Towards the better understanding of the
      pathophysiological mechanism underlying SS, we performed electrophysiological
      studies, in which multiple evoked potential studies were included, in 3 patients
      with SS. Somatosensory evoked potentials (SEPs) evoked by median nerve
      stimulation were all normal, but those evoked by the posterior tibial nerve
      stimulation showed a significant delay of the latency of P40. In the auditory
      brainstem response (ABR) studies, there were no reproducible responses of the
      brainstem origin. In the blink reflex studies, R2 latency was delayed in one
      patient. In visual evoked potential (VEP) studies, the latency of P100 was
      delayed in two of three patients, unless all the patients clinically showed no
      visual symptom. The nerve conduction velocity studies performed in peripheral
      nerves of upper and lower extremities were all normal. The abnormal findings of
      ABR and SEP may suggest that the acoustic nerve and the posterior funiculus of
      the spinal cord are involved, respectively. These findings are also in a good
      agreement with pathological findings of SS reported in the literature. In SS, the
      hemosiderine accumulation is usually less severe in the visual tract; however,
      the delay of VEPs may suggest the latent dysfunctioning of the visual system in
      SS. It is suggested that multiple evoked potential study is useful for clinical
      evaluation of SS.

PMID- 9592827
TI  - [Interhemispheric asymmetry exists in female in the N100m source position of the
      auditory evoked magnetic fields].
AB  - The N100m source of the auditory evoked magnetic fields (AEFs) is located more
      posterior in the left than the right hemisphere in male subjects. However,
      whether this asymmetry exists in female subjects is controversial. The present
      study, analyzed the N100m source positions of the AEFs due to monaural tone
      stimuli using a helmet-shaped 66-channel magnetoencephalography system (CTF
      Systems) in 62 right-handed normal adults (24 females and 38 males). The best fit
      sphere was calculated for each subject from the head shape reconstructed from
      three-dimensional magnetic resonance images. N100m source positions were
      estimated using a double-dipole model. The contralateral N100m response to the
      stimulated ear was measured relative to the midpoint of the bilateral auricular
      points. Statistical analysis used a standardized head size for each subject based
      on the mean value of all subjects (r = 8.27 cm). In females, the N100m dipole
      positions were 0.00 +/- 1.02 cm anterior in the left hemisphere and 0.35 +/- 0.74
      cm in the right (p < 0.02). In males, the N100m dipole positions were -0.31 +/-
      0.81 cm (mean +/- standard deviation) anterior in the left hemisphere and 0.61 +/
      0.78 cm in the right (p < 0.0001). The interhemispheric difference in the N100m
      positions was 0.35 +/- 0.65 in females and 0.92 +/- 0.77 in males (p < 0.005). In
      conclusion, the left hemispheric N100m is located more posterior to the right in
      both genders. However, this functional asymmetry is more evident in males, like
      previous findings of more evident anatomical asymmetry in males.

PMID- 9592828
TI  - [Correlation between event-related potentials and regional cerebral blood flow in
      chronic alcoholism].
AB  - We report a correlation between P300 and cerebral blood flow in 11 patients with
      chronic moderate alcoholism. The patients had been drinking more than 83 ml pure
      alcohol equivalent everyday for more than 10 years and did not have any other
      neurological diseases. The P300 latency was significantly longer in the chronic
      alcoholism group than in the age-matched healthy control group. There was a
      significant negative correlation between the P300 latency and the thalamus blood
      flow in the chronic alcoholism group. These findings suggest that there is a
      subclinical disturbance of cognitive function in chronic alcoholism and that the
      prolongation of P300 latency is related to the decrease in thalamus blood flow in
      chronic alcoholism.

PMID- 9592829
TI  - [Successive subcortical hemorrhages in the superior parietal lobule and
      postcentral gyrus in a 23-year-old female].
AB  - We report a non-hypertensive 23-year-old female with successive hemorrhages in
      parietal subcortical regions. She had first experienced a transient pain in the
      left upper extremity one month before admission. She noticed dysesthesia in the
      same limb and weakness on her left hand, and, five days after, visited our
      hospital because of suddenly developed convulsion in the limb and loss of
      consciousness for a few minutes. Neurological examination revealed distal
      dominant flaccid paresis, positive pathological reflex and touch and position
      sense disturbances in the affected limb. Brain CT detected two high-density areas
      in the parietal lobe. Brain MRI demonstrated an acute phase subcortical hematoma
      in the left postcentral gyrus and a subacute phase one in the left superior
      parietal lobule. SPECT indicated hypoperfusion in the left frontal and parietal
      cortex. Cerebral angiography showed no abnormal findings. Her symptoms gradually
      improved, but left ulnar-type pseudoradicular sensory impairment remained on
      discharge. We considered the hemorrhage in this patient have arisen from rupture
      of cavernous hemangioma, because she was relatively young, the hematomas were
      oval in shape and successively developed in the left parietal lobe. Our patient
      suggests that a subcortical hemorrhage in the post-central gyrus causes flaccid
      paresis and pyramidal tract involvement.

PMID- 9592830
TI  - [A patient with an ACTH-releasing thymic carcinoid tumor presenting with proximal
      muscle weakness].
AB  - We report a 36-year-old man with proximal dominant muscle weakness, thymic tumor,
      diabetes mellitus, hypokalemia, and increased levels of plasma ACTH and cortisol.
      The diagnosis of carcinoid tumor was made on the basis of pathological findings
      in the biopsied specimen of the thymic tumor. The proximal muscle weakness was
      considered to be due to steroid myopathy resulting from the overproduction of
      cortisol from the adrenal glands induced by the ectopic ACTH secreted by the
      thymic carcinoid tumor. Although thymoma in frequently associated with myasthenia
      gravis, we should also consider carcinoid tumors in patients with a thymic tumor
      presenting with a proximal muscle weakness.

PMID- 9592832
TI  - [Midbrain ptosis with diurnal fluctuation like myasthenia].
AB  - A 51-year-old man was admitted because of bilateral fatigable blepharoptosis with
      diurnal fluctuation. He had a tendency to take much instant foods before onset.
      On admission, he showed symmetrical bilateral ptosis, supranuclear upward gaze
      palsy and vertical diplopia. Ptosis mildly improved on lateral or upward gaze.
      Bell's phenomenon and pupillary response were intact. Intravenous edrophonium
      infusion test and serum antiacetylcholine receptor antibody were negative.
      Cranial MRI and CT demonstrated the lesion in the periaqueductal gray (PAG)
      region from superior colliculus to upper pontine level, which was remarkably
      enhanced by Gd-DTPA infusion. He was diagnosed as midbrain ptosis, probably due
      to atypical Wernicke's encephalopathy. It was conceivable that the PAG lesion
      might be contributory to fatigable blepharoptosis (pseudomyasthenia) and
      supranuclear upward gaze palsy in the present case, because the PAG controls
      levator palpebrae neurons of central caudal nucleus in oculomotor nucleus complex
      and receives afferents from the limbic system., reticular formation and posterior
      commissure.

PMID- 9592831
TI  - [Patho-MR imaging study in the putaminal margin in multiple system atrophy].
AB  - The slit hyperintensity of the lateral margin of the putamen in T2 weighted MRI
      is a characteristic finding in those patients with multiple system atrophy (MSA)
      involving extrapyramidal system. In spite of some speculations such as
      demyelination, gliosis, iron deposition or increased extracellular fluid, the
      nature of the abnormal signal intensity has still been remained uncertain. In
      this paper, we report the coincidental findings of pathology and magnetic
      resonance imaging of the putaminal margin in a case of MSA. The patient was sixty
      three years old woman with nine years history of intreatable parkinsonism, mild
      ataxia and dysautonomia. At six months prior to her death, 0.5T MRI showed the
      pontocerebellar system atrophy, slit hyperintensity in the bilateral outer margin
      and left inner margin of the putamen in T2 weighted image as well as linear
      hypointensity in T1 weighted image. The neuropathological examinations showed
      severe degeneration in the olivopontocerebellar and striatonigral systems, and
      glial cytoplasmic inclusion in widespread regions in the brain. The putamen
      showed severe degeneration with rarefaction. The intertissue space was observed
      at the outer putaminal margin in both sides and inner margin in left side, which
      seemed to be caused by severe shrinkage and rarefaction of the putamen. Thus,
      slit hyperintensity in the putaminal margin in MSA was disclosed to represent
      widened intertissue space.

PMID- 9592833
TI  - [MR diagnosis of spinocerebellar ataxia type 1 and spinocerebellar ataxia type
      2].

PMID- 9592834
TI  - [MRI findings in a patient with orbital cellulitis and meningitis].

PMID- 9592835
TI  - Children's cancer in the developing world: where are the girls?

PMID- 9592836
TI  - Bcl-2 expression in childhood leukemias: could it be used as a prognostic factor?

PMID- 9592837
TI  - Medical oncology: Tata Memorial Centre, Mumbai.

PMID- 9592838
TI  - The Giannina Gaslini Children's Hospital.

PMID- 9592839
TI  - Acute lymphoblastic leukemia with severe skeletal involvement: a subset of
      childhood leukemia with a good prognosis.
AB  - Skeletal radiographic abnormalities are common in children with acute
      lymphoblastic leukemia (ALL). The impact of severe skeletal involvement (SI) on
      survival and the correlation between SI and biological markers were analyzed.
      Therefore, radiographs and medical charts of 106 ALL patients who received a
      skeletal survey at the time of diagnosis and were treated at the University
      Children's Hospital Wurzburg between 1974 and 1995 were reviewed. On the basis of
      the skeletal survey, SI was quantified using a score. Fifty-nine patients (55%)
      showed radiographic abnormalities defined as metaphyseal banding (48%),
      periosteal reactions (11%), osteolysis (33%), osteosclerosis (31%), or osteopenia
      (22%). Children with severe SI (n = 32) presented with a higher rate of severe
      radiographic abnormalities such as geographic destructive osteolysis (37%; P <
      .001) and periosteal reactions (28%; P < .05) compared with children with
      moderate SI (0% and 4%, respectively). Patients with severe SI showed a lower
      peripheral blast count (P < .05) at diagnosis, a more frequent "prednisone good
      response" (P < .05), and a higher survival rate (83 +/- 7%; P < .05) than
      patients without SI (54 +/- 9%). Patients with moderate SI (n = 27) showed a
      higher hemoglobin concentration (P < .05), an enlargement of liver (P < .05) and
      spleen (P < .01), a higher BFM risk factor (P < .01), but still a higher survival
      rate (73 +/- 11%) than patients without SI (NS). Patients with severe SI had a
      higher (P < .001) DNA content of leukemic cells as measured by DNA index (DI)
      than patients without SI. Thirty-one percent of patients with severe SI, 22% of
      patients with moderate SI, and no patient without SI had a DI > 1.16. No patient
      with a DI < 1.0 presented with severe SI. The number of radiographic
      abnormalities in patients with SI correlated with the DI (rho: 0.46; P < .001).
      However, patients with euploidy (DI = I) and severe SI also had a higher (P =
      .05) survival rate (70 +/- 18%; n = 15) than euploid patients without SI (49 +/-
      11%; n = 24). Of the patients with severe SI, 78% had common ALL and 22% had an
      ALL type other than common ALL (P < .05). In patients with ALL types different
      from common ALL, severe SI was also associated with higher survival rates. We
      conclude that on the basis of clinical features, two distinct subgroups could be
      identified in terms of SI. Patients with clinically relevant severe SI had a
      better prognosis, a higher DI, and more frequently a common ALL than patients
      without SI. However, the impact of severe SI on prognosis was independent of DI
      and type of leukemia.

PMID- 9592840
TI  - Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age.
AB  - The aim of this study was to establish reference values and factors associated
      with serum AFP elevation in infants. Five hundred twenty-four samples collected
      from infants up to the age of 2 years at the University Hospital Dusseldorf
      (Germany) were analyzed. At birth mean serum AFP levels were 41,687 ng/ml in 256
      term babies and 158,125 ng/ml in 90 premature babies born before the 37th
      gestational week, excluding samples from children with factors known to be
      associated with AFP elevation. In the first 4 weeks of life, AFP levels decreased
      by 50% in 5.1 days in term babies. Between day 180 and 720 of life, AFP levels up
      to 87 ng/ml were within the 95.5% interval (assumed logarithmic normal
      distribution) with a mean of 8 ng/ml without a further decline. By the age of 2
      years the infants of this study had not reached adult serum AFP levels (0-6
      ng/ml).

PMID- 9592841
TI  - Bcl-2 expression and prognosis in childhood acute leukemia. Children's Cancer and
      Leukemia Study Group.
AB  - Bcl-2 expression and its prognostic value were evaluated in 42 children with
      acute leukemia. The Bcl-2 expression of the leukemic blast cells was measured
      quantitatively by flow cytometry and was further analyzed by the simultaneous
      immunostaining of Bcl-2 with the surface membrane antigens, DNA, Ki-67 antigen.
      All of the cases showed a consistent expression of Bcl-2 protein; virtually all
      leukemic lymphoblasts were Bcl-2 positive. Although the expression of Bcl-2
      varied widely from 7 to 80 x 10(3) MESF units, no significant difference was
      found in the mean value between the patients with acute lymphoblastic leukemia
      and those with acute myeloblastic leukemia. In more than half of the patients
      with AML, intraclonal heterogeneity of Bcl-2 expression was observed. The
      expression of Bcl-2 showed no apparent fluctuations during the different phases
      of the cell cycle. However, the proportion of Bcl-2-positive and -negative cells
      during the cell cycle was different between ALL and AML patients. In the ALL
      patients, few Bcl-2-negative cells were detected only in the GI phase, whereas in
      the AML patients Bcl-2-negative cells were detected in the S and G2/M phases, as
      well as in the G1 phase. No apparent difference was found in Bcl-2 expression
      between the Ki-67-negative noncycling population and the Ki-67-positive cycling
      population. Of the clinical features of these patients, only CD34 expression in
      the ALL patients was associated with high levels of Bcl-2 expression. In the 28
      untreated cases of ALL, high expression of Bcl-2 was not an unfavorable factor
      for the outcome of this disease.

PMID- 9592842
TI  - A seven-years experience in treatment of childhood ALL in Bulgaria.
AB  - After analyzing nonsatisfactory therapeutic results in the 1970s and early 1980s,
      the 81-01 treatment protocol of the Dana-Farber Cancer Institute was initiated in
      1987 in the Children's Oncohaematology Clinic in Sofia, Bulgaria. Two hundred
      thirty patients were enrolled with a period of observation of a minimum of 14 and
      a maximum of 97 months; the median age was 5.83 +/- 3.6 years. According to the
      original criteria, standard risk (SR) patients were 38.26% and high-risk (HR)
      patients 61.74%. The probability for event-free survival at the seventh year
      estimated with the Kaplan-Meier method for the total group was 0.67 +/- 0.04 (+/-
      SE) and 0.55 +/- 0.09 and 0.81 +/- 0.06 for HR and SR, respectively (P < .001).
      Improvement of therapeutic results in terms of remission failures, early deaths,
      patients lost to follow-up, and rate of relapses is discussed.

PMID- 9592843
TI  - Infections occurring during the courses of anticancer chemotherapy in children
      with ALL: a retrospective analysis of 59 patients.
AB  - In a retrospective analysis we evaluated the occurrence of infections in 59
      children with acute lymphoblastic leukemia (ALL) during the entire duration of
      their anticancer chemotherapy. We recorded a total of 245 infection episodes, 118
      (50%) being during neutropenia and 119 (50%) during nonneutropenia. The
      infections most commonly detected during neutropenia were fevers of undetermined
      origin (36%), clinically or microbiologically defined focal infections (33%), and
      bacteremias (28%). During nonneutropenia, upper respiratory tract infections
      (55%) were the most common. Patients needed hospitalization for infections for a
      total of 1951 days (i.e., a mean of 33 days per patient) and the mean number of
      infection episodes was 4.2 per patient. Recurrent fever developed in 21% of the
      children with bacteremia. Mortality caused by bacteremias was 10%. Infections
      during the chemotherapy of ALL were a significant cause of morbidity in children,
      but mortality was low.

PMID- 9592844
TI  - Immunophenotyping pediatric leukemias in Kelantan, Malaysia.
AB  - This study reviewed the immunophenotyping results of children with acute leukemia
      in Kelantan, Malaysia. In the 3.5-year period (January 1994 to June 1997), 45
      cases were identified. All children were under the age of 12 years and the
      predominant ethnic group was Malay. Thirty-six cases (80%) were acute
      lymphoblastic leukemia (ALL) and 9 cases (20%) were acute myeloblastic leukemia
      (AML). Of the ALL cases, 3% were of B-cell and 22% of T-cell origin, and 96% of
      the B-lineage ALL were CD10 positive. All the AML cases expressed CD33 and 78%
      were positive for CD13. The incidence of mixed-lineage leukemias was 13.8% for
      My+ ALL and 11.1% for Ly+ AML.

PMID- 9592845
TI  - Maffucci's syndrome as cause of chronic liquorrhea.
AB  - We present the case of a 14-year-old girl suffering from Maffucci's syndrome, a
      rare ailment belonging to the group of osteochondrodysplasias. At the age of 6
      months, a diffuse swelling first appeared in the girl's right cheekbone region
      and the periauricular area. Because of recurrent meningitis with massive
      otoliquorrhea, several surgical revisions were performed, beginning at the age of
      4 years. The histological and immunohistochemical diagnosis showed hemangioma and
      lymphangioma with enchondroma. As a peculiarity of our patient's diagnosis, we
      found multiple bone defects apparently caused by venous and lymphomatous
      angiomatosis. There was also enchondromatosis of the skull base and the upper
      cervical vertebrae, which caused the recurrent otoliquorrhea and rhinoliquorrhea.
      A fistula closure was undertaken through a retromastoidal, suboccipital approach
      and fascial graft of the posterior cranial fossa.

PMID- 9592846
TI  - Basal cell carcinomas developing in a case of medulloblastoma associated with
      Gorlin's syndrome.
AB  - We report a case of a 20-year-old male with Gorlin's syndrome (nevoid basal cell
      carcinoma syndrome), developing multiple basal cell carcinomas within irradiation
      fields 10 years after the treatment of medulloblastoma.

PMID- 9592848
TI  - General practice and secondary prevention.

PMID- 9592847
TI  - Neutropenia complicating Rh-hydrops fetalis: the effect of treatment with
      recombinant human granulocyte colony-stimulating factor (rhG-CSF).
AB  - Neutropenia is a less commonly encountered feature of Rh hemolytic disease of the
      newborn, and its management may be problematic. Two newborn infants with
      neutropenia complicating Rh incompatibility-induced hydrops fetalis were treated
      with intravenous recombinant human granulocyte colony-stimulating factor (rhG
      CSF), 5 micrograms/kg/day for 5 days. Both patients responded to therapy with a
      rapid and persistent increase of their neutrophil counts to normal values. The
      treatment was well tolerated and no adverse clinical events were observed. rhG
      CSF induces a significant increase in peripheral absolute neutrophil counts of
      neutropenic neonates with Rh hydrops fetalis and was well tolerated. The
      contribution of rhG-CSF to clinical recovery warrants further investigation.

PMID- 9592849
TI  - [Demographic study of ages and causes of death which contribute to gender
      disparities in life expectancy--case of Switzerland (1969-1993)].
AB  - BACKGROUND: In Switzerland, women live about six years more than men. The purpose
      of our study was to measure and describe the respective contributions of the
      various age groups and causes of death to the difference in life expectancy at
      birth between men and women. METHODS: With an analytical demographic method, this
      difference in life expectancy can be distributed according to age and cause of
      death. The contribution of each age and cause can be discussed. RESULTS: All ages
      and quite all causes of death contribute to overmortality in men. Age groups over
      50, as well as circulatory diseases and malignant neoplasms, contribute most to
      gender disparities in longevity while violent deaths play a less important role.
      CONCLUSIONS: Any attempt to reduce gender mortality disparities would involve the
      modification of a number of etiological factors, including biological factors or
      those linked to lifestyle.

PMID- 9592850
TI  - [Mortality in the French paper and pulp industry].
AB  - BACKGROUND: The objective was to describe a possible cancer mortality risk in
      relation with the occupational exposure within an International study co
      ordinated by the International Agency for Research on Cancer. METHODS: An
      epidemiological cohort study was set up to assess the mortality in four French
      pulp and paper companies. The four cohorts were followed up from January 1st 1968
      to December 31st 1992. The causes of death were ascertained by matching with the
      national file of causes of death. RESULTS: The full cohort consisted in 5,529 men
      and 876 women. The total numbers of subjects deceased between 1968 and 1992 were
      respectively 708 and 34. Causes of death could be traced for 98%. The observed
      mortality was significantly lower than the expected for all causes of deaths (SMR
      = 0.86) as well for all deaths by cancer (SMR = 0.87). The analysis by
      departments showed an excess mortality by cancer of the pancreas in the wood
      preparation department (SMR = 3.14) as well as in the paper production department
      (SMR = 2.04). CONCLUSIONS: In absence of any prior hypothesis, it is difficult to
      assign an occupational origin to these observed excesses. The future results of
      the international study will enable us to interpret these results more precisely.

PMID- 9592851
TI  - [Tobacco and ectopic pregnancy. Arguments in favor of a causal relation].
AB  - BACKGROUND: The risk associated with smoking has been studied for a long time in
      fertility epidemiology. This paper reviews the association between smoking and
      ectopic pregnancy (EP) using results collected in our previous studies. It
      provides arguments for a causal interpretation of this association. METHODS: Data
      came from three case-control studies performed between 1988 and 1996 and from the
      register of ectopic pregnancies in Auvergne (France) from 1992 to 1995. The
      methods are those classically used in the analysis of case-control studies.
      RESULTS: The risk of EP increased significantly with smoking (p < 0.01): the
      adjusted OR are 1.5 for 1-9 cigarettes a day, 2.0 for 10-19 cigarettes a day, and
      2.5 for more than 20 cigarettes a day. The attributable risk of smoking ranged
      between 17% and 32% according to the study. Similarly, the risk of EP recurrence
      increased significantly with smoking (p < 0.02): after adjustment, OR = 1.3 for 1
      9 cigarettes a day, OR = 1.5 for 10-19 cigarettes a day, and OR = 1.7 for more
      than 20 cigarettes a day. Finally, smoking was associated with the site of EP.
      CONCLUSIONS: Thus there is a large body of arguments towards a causal
      relationship between smoking and EP. This provides additional arguments to
      persuade women to stop or to reduce smoking, especially hypofertile women.

PMID- 9592853
TI  - Knowledge and participation of general practitioners in cervical cancer
      screening: survey in a French pilot area.
AB  - BACKGROUND: Eighteen months after the beginning of a pilot cervical cancer
      screening program in a French district of 484,770 inhabitants, a survey was
      performed among general practitioners (GP). The aim was to assess their knowledge
      of the screening policy, the factors related to their participation, the
      difficulties they encounter and their training needs. METHODS: A random sample of
      168 GPs was taken from a medical association file. Eighty-seven percent of the
      physicians agreed to be interviewed by phone. The questionnaire was standardized
      and made up of open questions. RESULTS: On the whole, screening policy was not
      well known to the GPs: 58 percent believed screening had to begin before age 21
      and could be discontinued before age 61. Sixty percent of GPs declared that they
      provided women with written information, and 49 percent that they offered Pap
      smears to all women. Seventy-nine percent said that they took Pap smears, but 39
      percent claimed they had difficulty mainly due to women's reluctance or to
      technical problems. Few GPs expressed training needs. Reported difficulties and
      expressed need for training increased with the physician's age. GP concern for
      public health activities increased their participation in the campaign.
      CONCLUSION: Pilot programs have to implement measures which can help GPs to deal
      with community care and screening activities since GP involvement is one of the
      essential conditions of successful organized screening.

PMID- 9592852
TI  - [Estimation of the efficacy of three strains of mumps vaccines during an epidemic
      of mumps in the Geneva canton (Switzerland)].
AB  - BACKGROUND: The number of mumps cases reported in Switzerland markedly increased
      from 1993 to 1995 although vaccination coverage against mumps had risen steadily
      since the national MMR immunization program was launched in 1987. In 1991, an
      estimated 80% of children 27 to 36 month-old were immunized against mumps. The
      purpose of the present study was to assess the hypothesis that the epidemic was
      the consequence of a low vaccine efficacy of the Rubini strain--a mumps vaccine
      strain that has been widely used in Switzerland. METHODS: Vaccine efficacy was
      assessed by measuring secondary attack rates among immunized and nonimmunized
      children 16 year-old or younger who wre family contacts of cases. RESULTS: From
      February 1993 to April 1996, Geneva pediatricians reported 283 primary cases of
      mumps and 63 secondary cases. Estimate of vaccine efficacy was equal to 6.3% (95%
      CI: -45.9; 39.8) for the Rubini strain, as compared to 73.1% (95% CI: 41.8; 87.6)
      for the Urabe Am 9 strain, and 61.6% (95% CI: 0.0; 85.4) for the Jeryl Lynn
      strain, two vaccine strains of mumps that had also been used in Geneva.
      CONCLUSION: Our study supports the hypothesis that the Rubini vaccine strain of
      mumps does not confer sufficient long-lasting protection against mumps.

PMID- 9592854
TI  - [Information campaign on child care practices: measure of the effects on sleep
      position and sudden infant death syndrome].
AB  - BACKGROUND: To define the prevalence of the child care practices questioned in
      the sudden infant death syndrome (SIDS), especially the prone sleep position,
      before and after an information campaign. To evaluate the effects of this action
      on the postneonatal mortality. METHOD: A population survey was conducted in four
      French departments among mothers of infants born in March 1994 and March 1995 and
      aged 5 days and 2.5 months. A specific information campaign was conducted among
      health personnel in October 1994. RESULTS: After the information campaign, the
      prevalence of prone sleeping dramatically decreased at both ages studied: from
      6.8% to 1.1% at 5 days and from 24.5% to 7.2% at 2.5 months. Duvets were used
      less whereas the other practices (bed sharing, using pillow, breastfeeding,
      maternal smoking) did not change. The postneonatal SIDS rate significantly
      decreased, from 1.1 p. 1000 live births in 1994 to 0.7 in 1995, the mortality
      from others causes also declined; the overall postneonatal mortality was 2.7 p.
      1000 before the action and 2.1 p. 1000 after. CONCLUSION: The sleeping position
      which is the main factor questioned in SIDS was modified, and the postneonatal
      mortality decreased. The specific action conducted for the present
      epidemiological research is probably not the only contributor in these positive
      results.

PMID- 9592855
TI  - [Health promotion for immigrant women in Quebec].
AB  - Over the past fifteen years, the Canadian population has undergone increasing
      cultural diversification. Many researchers have investigated the role of culture
      with respect to social and health services. Most studies confirm the fact that
      increased cultural diversification related to immigration challenges the public
      health system in many ways. Certain groups, such as economically challenged
      immigrant women, may pose even greater problems to the health system. While these
      individuals are in relatively good health upon arrival to Canada, there is a need
      to ensure that adequate health promotion as well as disease prevention strategies
      are instituted. It is important to examine the concepts of health promotion and
      disease prevention through a cultural perspective. Little research has been done
      in this area. Concepts of promotion and prevention as they are understood by
      immigrants may not always coincide with North American or European definitions.
      Therefore, it is essential to consider life conditions that surround potential
      health promotion and prevention behaviors of immigrants. Empowerment, economic
      integration and acculturation are among the many factors that need to be taken
      into account when studying immigrants' health promotion behavior. Here, we
      present a critical analysis of current knowledge in this field. This is followed
      by research recommendations aimed at facilitating the development of health
      promotion and prevention strategies that are appropriate to the needs of
      Canadian, and more specifically of immigrant women in Quebec.

PMID- 9592856
TI  - [Delayed health effects of pesticides: review of current epidemiological
      knowledge].
AB  - The use of pesticides has extensively grown in the last decades, regardless of
      the economic level of the countries. This led to great improvements in
      agriculture but also a threat for human health. Short term effects are quite well
      known through approval procedures for pesticides. On the other hand, long term
      effects are not properly assessed. A review of epidemiologic knowledge is
      presented here. Epidemiologic studies on pesticides have found associations with
      long-term effects on health mainly in three fields: cancer (especially
      hematological cancer), neurotoxic effects (polyneuropathy, neuro-behavioral
      hazards, Parkinson's disease), and reproductive disorders (infertility, birth
      defects, adverse pregnancy outcomes, perinatal mortality). These conclusions have
      been obtained despite difficulties in exposition assessment due to the
      retrospective nature of the studies. But the continuous development of pesticide
      use in agriculture, and also in domestic environment, emphasizes the need for
      epidemiologic studies on long-term effects of pesticides relying on accurate
      exposure assessment.

PMID- 9592857
TI  - [Computerizing doctors' office, a public health opportunity not to be missed].

PMID- 9592858
TI  - [Liver cancer in male hemophiliacs].

PMID- 9592859
TI  - [Controversies about congenital malformations after in vitro fertilization using
      sperm microinjection].

PMID- 9592860
TI  - Production of platelet-derived growth factor in aseptic loosening of total hip
      replacement.
AB  - Aseptic loosening is the predominant cause of total hip implant failure. It has
      been assumed that a layer or membrane, containing macrophages, fibroblasts and
      vascular endothelial cells, of synovial-like tissue develops at the implant-to
      bone interface almost invariably and, with time, somehow leads to loosening of
      the components from the surrounding bone. These cells produce a variety of
      cytokines and proteolytic enzymes which stimulate bone resorption. Platelet
      derived growth factor (PDGF) may be one of the cytokines which stimulate bone
      resorption and contribute to aseptic loosening in total hip replacement (THR).
      Synovial-like membrane from the implant or cement-to-bone interface (n = 10) and
      pseudocapsule (n = 10) were obtained from ten patients operated on for aseptic
      loosening of THR. As a control, nine samples of connective tissues were obtained
      from patients who had mandibular or maxillary fractures fixed with bone implant.
      The avidin-biotin-peroxidase complex (ABC) method with polyclonal rabbit anti
      human IgG against the A-chain and B-chain of PDGF was used for staining. ABC
      alkaline phosphatase-anti-alkaline-phosphatase double staining with monoclonal
      mouse anti-human fibroblast IgG1 and CD68 antibodies was used to ascertain the
      cellular origin of PDGF. Results of the PDGF staining were quantitated by a semi
      automatic VIDAS image analysis system. The PDGF-A and PDGF-B chain containing
      cells were found in all periprosthetic tissues, in particular in macrophages with
      phagocytosed particulate debris, but to some extent also in fibroblasts and in
      endothelial cells. The numbers of PDGF-A and PDGF-B chain positive cells per mm 2
      in synovial-like interface membrane (1881 +/- 486 and 1877 +/- 214) and
      pseudocapsule (1786 +/- 236 and 1676 +/- 152) were higher (P < 0.01) around loose
      THR than in control tissue (821 +/- 112 and 467 +/- 150), respectively. The
      results of the present study suggest that PDGF is preferably expressed by
      macrophages, which to an increased extent produce it in the synovial-like
      interface membrane and pseudocapsular synovial-like membrane. Because of its role
      in bone resorption, it may well play a role in periprosthetic bone loss and
      aseptic loosening and deserves more detailed study as a mediator and potential
      target in the modulation or prevention of loosening of THR.

PMID- 9592861
TI  - Molecular and genetic characterization of two anti-DNA antibodies derived from
      patients with systemic lupus erythematosus.
AB  - Anti-double stranded(ds) DNA antibody is one of markers of systemic lupus
      erythematosus (SLE). Two human monoclonal anti-DNA antibody-producing cell lines
      were established from two SLE patients. One cell line secreted IgG isotype
      antibody (KSUG) and the other secreted IgM isotype antibody (KSUN). The light
      chains of the two immunoglobulins were lambda chains. The nucleotide sequences
      for the immunoglobulin variable region genes of the two antibodies were
      determined and compared to germline sequences. The heavy and lambda light chains
      of KSUG were VH3 family and V lambda IIIb, respectively. The heavy and lambda
      light chains of KSUN were VH4 family and V lambda IX, respectively. Antibody
      KSUG, IgG isotype, showed somatic mutations, whereas KSUN, IgM isotype, used the
      germline gene without mutation. These findings reconfirm the current paradigms
      that IgM anti-DNA antibodies are produced by utilizing germline genes whereas IgG
      anti-DNA antibodies are produced by somatic mutations.

PMID- 9592862
TI  - Elderly onset rheumatoid arthritis and polymyalgia rheumatica: ultrasonographic
      study of the glenohumeral joints.
AB  - The glenohumeral joints of 32 patients (aged 60 or above) were examined using
      ultrasonography. Thirteen patients were suffering from characteristic polymyalgia
      rheumatica (PMR) symptoms. In contrast 19 other patients initially had similar
      complaints, but were diagnosed as having elderly onset rheumatoid arthritis
      (EORA) upon development of typical symptoms. Ultrasound examination revealed
      glenohumeral joint inflammation in 61% (8 out of 13) of the patients with PMR and
      63.2% (12 out of 19) of the patients with EORA. These findings suggest that a
      subgroup of patients with PMR and EORA suffers from shoulder joint inflammation
      and this synovitis/bursitis/intraarticular effusion might play an important role
      in the understanding of their symptoms. We conclude that overlapping forms of PMR
      and a predominate rheumatoid factor negative subgroup of EORA might exist and
      should be further characterized.

PMID- 9592863
TI  - HLA DRB1* alleles in rheumatoid nodulosis: a comparative study with rheumatoid
      arthritis with and without nodules.
AB  - Rheumatoid nodulosis (RN) is a rare condition associating rheumatoid nodules,
      episodes of arthritis, cystic bone lesions and, generally, positive rheumatoid
      factors (RF). It is considered a benign variant of rheumatoid arthritis (RA). In
      this study, we determined the HLA DRB1* alleles of our RN patients and compared
      the distribution of these alleles to those of 74 healthy controls and 104 RA
      patients with and without nodules. Four RN patients were observed. All had
      subcutaneous nodules and RF were negative in three patients. Of the 104 RA
      patients, 18 had nodules (nodRA). Systemic manifestation (including vasculitis,
      peripheral neuropathy or lung involvement) were found in seven of these nodRA
      cases (33.8%) and most had positive RF and erosive changes on X-rays. Only one RN
      patient had a RA-associated allele (DRB1*0101). The frequencies of the HLA DRB1*
      alleles encompassing the "rheumatoid" shared epitope were similar to those of
      other RA series: *0101, 34.6% (P = 0.03 compared with controls); *0401, 26.9% (P
      < 0.0001); *0404, 12.5% (P = 0.04); *0405, 4.8% (P = 0.8); *1001, 8.6% (P = 0.5).
      Of the nodRA and seronegative RA patients, 77.7% and 53.3%, respectively,
      presented the shared epitope. Thus, there was a tendency to decreased expression
      of the RA-associated alleles in RN (25%) compared with nodRA and seronegative RA
      patients. This study is restricted by the small number of tested RN patients, but
      the results suggest that the RA-associated alleles are poorly expressed in RN.

PMID- 9592864
TI  - Pathological significance of elevated soluble CD14 production in rheumatoid
      arthritis: in the presence of soluble CD14, lipopolysaccharides at low
      concentrations activate RA synovial fibroblasts.
AB  - In order to establish what contributes to elevated levels of soluble CD14 (sCD14)
      in rheumatoid arthritis (RA) plasma, levels of sCD14 were compared in RA-paired
      plasma and synovial fluids and, further, in the culture supernatants of monocyte
      rich fractions from patients with RA and healthy donors, and macrophage-rich
      fractions from RA synovial tissues. The results showed elevated sCD14 in RA
      synovial fluid in 9 of 16 paired samples and in RA macrophage-rich fractions,
      suggesting that elevated sCD14 in RA plasma might be due to the sCD14 production
      by RA synovial macrophages. From the molecular analysis of elevated sCD14, the
      proteolytic cleavage of membranous CD14 (mCD14) was important in accelerated
      sCD14 production. Lipopolysaccharides (LPS) at low concentrations and sCD14
      increased the ICAM-1 expression on RA synovial fibroblasts. This result implies
      that in vivo RA synovial fibroblasts may be sensitive to LPS in the presence of
      sCD14 and LPS-binding protein (LBP).

PMID- 9592865
TI  - Treatment of DMARDs-resistant rheumatoid arthritis with minocycline: a local
      experience among the Chinese.
AB  - We report a local experience with minocycline (100 mg b.i.d.) in treating Chinese
      patients with rheumatoid arthritis (RA) who were resistant to the conventional
      disease-modifying antirheumatic drug (DMARD) treatment. In contrast to a
      preliminary observation in seven patients with rheumatoid arthritis, minocycline
      was effective and safe in treating our patients when added to the previous,
      relatively ineffective DMARD regimen. The antirheumatic effect of minocycline was
      impressive early in the first month. Drug compliance was fair; all patients
      continued to receive the study drugs, with no obvious adverse drug reactions. The
      reason why minocycline showed dramatic effects in reducing disease activity
      remains to be determined; however, minocycline-associated immune modulation, as
      indicated in this study, may be one of the important mechanisms in its
      antiarthritic effects.

PMID- 9592866
TI  - Activated protein C resistance in Behcet's disease.

PMID- 9592867
TI  - Ischemic heart disease in Behcet's syndrome.

PMID- 9592869
TI  - [Contribution of mectizan to the control of onchocerciasis. Impact on ocular
      lesions].

PMID- 9592868
TI  - [Onchocerciasis and the Mectizan donation program].

PMID- 9592870
TI  - [Contribution of mectizan to the control of onchocerciasis. Effect on
      transmission: evaluation of 9 years of treatment in West Africa].

PMID- 9592871
TI  - [Contribution of mectizan to the control of onchocerciasis. Effect on
      transmission after 8 years of treatment].

PMID- 9592872
TI  - [The onchocerciasis control program in West Africa (OCP): essential
      characteristics].

PMID- 9592874
TI  - [Onchocerciasis control in Senegal: evaluation of 10 years of control].

PMID- 9592873
TI  - [The beginning of the OPC and the status of onchocerciasis in western Africa
      before control measures].

PMID- 9592875
TI  - [Onchocerciasis in the Ivory Coast].

PMID- 9592876
TI  - [Onchocerciasis in West Africa. Strategies for mass treatment under community
      directives in Ghana].

PMID- 9592878
TI  - [Onchocerciasis in African countries not included in the onchocerciasis control
      program].

PMID- 9592877
TI  - [The African onchocerciasis control program: essential characteristics].

PMID- 9592879
TI  - [Onchocerciasis in Tanzania].

PMID- 9592880
TI  - [Onchocerciasis control program in Chad: the Mectizan donation].

PMID- 9592882
TI  - [The placement of partnerships for Mectizan distribution systems].

PMID- 9592881
TI  - [The Mectizan donation program in Gabon: progress and perspectives of
      distribution in the focus of onchocerciasis (1991-1997)].

PMID- 9592883
TI  - [Partnerships and the distribution of Mectizan. The role of a non-governmental
      development organization in a country with endemic onchocerciasis].

PMID- 9592884
TI  - [Improvement in the quality of life in rural Africa (AFRICARE) in the face of
      onchocerciasis in Chad (Mectizan donation program)].

PMID- 9592885
TI  - [Parnerships and the distribution of Mectizan. The example of the onchocerciasis
      control program].

PMID- 9592886
TI  - [Partnerships and the distribution of Mectizan. Ministries of health].

PMID- 9592887
TI  - [Partnerships and distribution of Mectizan. Sector investment programs for an
      integrated approach to investment loans].

PMID- 9592888
TI  - [Partnerships and distribution of Mectizan. Distribution of ivermectin in
      countries at war].

PMID- 9592889
TI  - [Mectizan and onchocerciasis: 10 years of Mectizan in Africa, a partnership for
      prolonged success].

PMID- 9592890
TI  - [The strategic role of information, education and communication in treatment
      programs using ivermectin (Mectizan) under community directives].

PMID- 9592891
TI  - [Distribution and treatment using ivermectin under community directives].

PMID- 9592892
TI  - [Indication of Mectizan in human medicine other than onchocerciasis].

PMID- 9592893
TI  - [Q fever with endocarditis: clinical presentation and serologic follow-up of 21
      patients].
AB  - AIM OF THE STUDY: The purpose of this study was to analyse the clinical and
      serological follow-up in 21 patients with Q fever endocarditis in Switzerland
      from 1981 to 1993. PATIENTS AND METHODS: Criteria for Q fever endocarditis were
      the following: Coxiella burnetii phase I IgG > 1 : 2560 and IgA > 1 : 20 by
      indirect immunofluorescence. Methods to confirm the diagnosis include
      immunohistochemical demonstration of C. burnetii by microscopy in valvular
      material (1 case) and inoculation of this material in experimental animals (10
      cases). Information on clinical course of the disease, laboratory abnormalities
      and treatment were obtained by chart review and a questionnaire sent to
      physicians who requested the serological tests for Q fever. RESULTS: The average
      age of the patients was 47 years (15 men and 6 women). 64% of patients had a
      history of environmental exposure to C. burnetii. The median time of
      symptomatology before diagnosis was 5 months (1-108). 19/21 patients had valvular
      lesions, and 2/21 vascular Dacron prosthesis. Most patients presented with fever
      (18/21), congestive cardiac failure (14/21), weight loss (12/21), anemia (6/19),
      or thrombocytopenia (6/19). All the patients required antibiotic treatment.
      Cardiac surgery was performed in 15/21 patients. For 10 patients the geometric
      mean serological follow-up included at least titers at time of diagnosis (IgG
      anti-phase I antibodies 1 : 27024, IgA anti-phase I antibodies 1 : 685), at the
      end of therapy (IgG anti-phase I antibodies 1 : 2941, IgA anti-phase I antibodies
      1 : 153) and 6 months after the end of therapy (IgG anti-phase I antibodies 1 :
      368, IgA anti-phase I antibodies 1 : 40). The fall in anti-phase I titers was
      significant. During the clinical and serological outcome (median of 60 months and
      69 months respectively) there was no recurrence of endocarditis and antibody
      titers to C. burnetii phase I remained low. Two patients died during the
      observation period, one from lung cancer, while the cause of death in the other
      was unknown. CONCLUSIONS: Serology is the key to Q fever diagnosis. The duration
      of treatment, and the values to be used to establish cure of endocarditis, are
      not clearly defined. During the clinical and serological outcome (median of 60
      months and 69 months respectively) there was no recurrence of endocarditis and
      antibody titers to C. burnetii phase I remained low.

PMID- 9592894
TI  - [Parenteral iron therapy: problems and possible solutions].
AB  - To investigate whether there are differences in the frequency of ADRs (adverse
      drug reactions) to parenteral iron preparations, we compared the results of 4
      different data collections which contain observations in particular on i.m. or
      i.v. iron dextran and i.v. iron hydroxide sucrose complex, primarily in relation
      to anaphylactic/anaphylactoid reactions and common exanthemas. 1. In 206 patients
      of the department of general internal medicine in a city/teaching hospital (in
      association with the Swiss Foundation for Comprehensive Hospital Drug Monitoring-
      CHDM), 4 probably allergic reactions to i.m. iron dextran were found, one with
      acute severe dyspnea, cyanosis and flush, 3 with slight generalized, probably
      allergic reactions. Data from the USA on i.v. iron dextran do not show marked
      differences in the frequency of ADRs as compared with our data with i.m.
      administration. 2. A group of 400 otherwise healthy patients of the obstetric
      department of Zurich University Hospital were treated with i.v. iron sucrose for
      anemia due to iron loss during pregnancy or following childbirth. Seven
      generalized skin reactions, 4 in the form of flush and 3 of common exanthema,
      occurred. 3. In a retrospective study on patients on maintenance hemodialysis
      with chronic renal insufficiency and anemia, a questionnaire was answered by the
      medical heads of 17 selected hemodialysis units in Switzerland. Response was
      100%. During around 8100 patient-years with approximately 160,000 ampoules of
      iron sucrose (with 100 mg elementary iron), not a single life threatening
      reaction was observed; only 5-7 situations of rapidly reversible blood pressure
      fall occurred, some 10 with flush, and one each with urticaria and
      vomiting/diarrhea. 4. The relatively good tolerance of i.v. iron sucrose in
      patients with chronic renal failure may be due either to reduced immune
      competence in patients with chronic renal insufficiency and/or to the use of the
      preparation itself, or probably both. 5. In ADRs of allergic appearance to iron
      sucrose, the 7 generalized skin reactions occurred on the first day of the
      injections, as did those under iron dextran. Preexisting hypersensitivity must be
      taken into consideration. 6. If our experience is confirmed, preventive measures
      with i.v. iron sucrose, mainly in patients with chronic renal insufficiency,
      could be reduced.

PMID- 9592895
TI  - The occurrence of percutaneous injuries to health care workers: a cross sectional
      survey in seven Swiss hospitals.
AB  - OBJECTIVES: In 1995, a cross sectional survey was conducted in 7 Swiss hospitals
      to estimate the incidence of percutaneous injuries among nurses, surgeons,
      anesthetists and domestic personnel, and to describe the circumstances of these
      injuries and the reporting process within the hospital. METHODS: An anonymous
      questionnaire was distributed and filled out on-site in the case of nursing staff
      and domestic personnel, and was sent by post to physicians (anesthetists and
      surgeons). Participants were asked to report in detail on percutaneous injuries
      of the last workday and the last working month (nurses and physicians), and of
      the last month and the last year for domestic personnel. The overall response
      rate was 72%, representing a total of 3116 health care workers. RESULTS: The
      annual incidence rates of percutaneous injury with material contaminated with
      blood or other biological fluids were calculated by type of worker for the two
      available units of time. For nurses, the incidence was 0.49 and 2.23, for
      surgeons 4.28 and 11.05, for anesthetists 2.11 and 3.14, and for domestic
      personnel 0.11 and 0.17 respectively. Most of the injuries occurred in a "normal"
      situation (no emergency, no stress, no fatigue) and were described as avoidable.
      Compliance with universal precautions was not optimal and declaration rates
      within the hospital rather low (nurses 39.7%, physicians 3.4%, domestic personnel
      87.9%). CONCLUSION: Percutaneous injuries with blood-contaminated material are
      frequent in health care workers, and are not always adequately assessed because
      of under-reporting of accidents within the hospital. This may result in
      underestimation of current occupational exposure of health care workers to HIV
      and other blood-borne viruses.

PMID- 9592896
TI  - [Clinical use of contrast-enhanced MR angiography].
AB  - Compared to other non-invasive MR-angiography techniques, contrast-enhanced MR
      angiography is a robust imaging technique in the assessment of the arterial
      vascular system. This is due to the use of three-dimensional data acquisition,
      non-nephrotoxic paramagnetic contrast and short acquisition times. Clinical
      applications include the evaluation of the thoracic and abdominal arterial
      vessels. With the refinement of this technique also small peripheral arteries of
      the extremities can be imaged and an entire non-invasive diagnostic work-up of
      the peripheral arteries will be possible.

PMID- 9592897
TI  - [Leg weakness in cytoalbumin dissociation in cerebrospinal fluid].

PMID- 9592898
TI  - Langerhans cell histiocytosis: unusual skeletal manifestations observed in thirty
      four cases.
AB  - OBJECTIVE: Unusual manifestations are occasionally encountered in Langerhans cell
      histiocytosis and may be a source of confusion. The objective of this study was
      to determine the frequency of occurrence of the unusual manifestations in our
      case material. DESIGN AND PATIENTS: Thirty-four children, average age 4.4 years
      (range 3 months to 16 years) with 262 skeletal lesions of biopsy-proven
      Langerhans cell histiocytosis (LCH) were retrospectively reviewed to determine
      the frequency of occurrence of unusual manifestations defined either as an
      atypical location of a skeletal lesion or an atypical radiographic appearance of
      the lesion. RESULTS: Twenty-four unusual lesions were found in this retrospective
      review. Among these were epiphyseal lesions, transphyseal lesions, extracranial
      'button' sequestra, posterior vertebral arch lesions, dural extension of
      vertebral lesions, and fluid-fluid levels. The finding of fluid-fluid levels has
      not previously been described in the radiologic literature. Involvement of
      unusual sites included clavicles and small bones of the hands and feet.
      CONCLUSIONS: Radiographic, computed tomographic, and magnetic resonance imaging
      of LCH yield a variety of unusual manifestations. Recognition of these varied
      appearances of LCH may prevent confusion of such appearances with other
      pathologic processes. When the unusual manifestation occurs as the initial
      finding of the disease, LCH should be included in the differential diagnosis.

PMID- 9592899
TI  - Surface-based hemangioma of bone: three case studies and a review of the
      literature.
AB  - Three cases of surface-based hemangiomas were reviewed. The cases illustrate the
      plain film and magnetic resonance imaging findings of these benign tumors, which
      can appear quite aggressive, mimicking more aggressive neoplasms. Each of the
      patients underwent en bloc excision, and pathologic evaluation to determine the
      diagnosis. To date, there has been no evidence of recurrence.

PMID- 9592900
TI  - Spondyloepiphyseal dysplasia with accumulation of glycoprotein in the
      chondrocytes: spondyloepiphyseal dysplasia, Stanescu type.
AB  - OBJECTIVE: To clarify the phenotype in a bone dysplasia termed
      "spondyloepiphyseal dysplasia with accumulation of glycoprotein in the
      chondrocytes" by Stanescu et al. DESIGN AND PATIENTS: Subjects comprised two
      definitive cases of one family and one probable case of another family.
      Histologic examination in one patient warranted the diagnosis of the first
      family, whereas the diagnosis of the second family was based solely on clinical
      and radiologic grounds. RESULTS: Pedigrees revealed an autosomal dominant mode of
      transmission. All three patients shared painful large joints with joint
      restriction, progressive contracture with osseous expansion of the finger joints,
      and normal height despite the presence of a short trunk. Moderate platyspondyly,
      hypoplastic ilia, epiphyseal flattening with metaphyseal splaying of the tubular
      bones, and most characteristically, broad, elongated femoral necks with striking
      coxa valga were identical in all patients, but the patient of the second family
      showed severe brachydactyly unlike the other two patients. Histologic examination
      revealed PAS-positive, amylase-resistant intracytoplasmic inclusion bodies in the
      chondrocytes, corresponding to dilated rough endoplasmic reticulum filled with
      moderately electron-dense materials found by electron microscopy. CONCLUSION: The
      manifestations of our patients are sufficiently characteristic to constitute a
      distinct entity.

PMID- 9592901
TI  - "Tower vertebra": a new observation in sickle cell disease.
AB  - BACKGROUND: Skeletal abnormalities are common in sickle cell anemia. Ischemia,
      infarction, and growth disturbance of the thoracic and lumbar vertebral bodies
      are among the most common abnormalities, and can suggest the diagnosis
      radiographically. DESIGN AND PATIENTS: We recently encountered two adult patients
      in whom vertebrae had grown abnormally in height adjacent to infarcted short
      vertebrae. We then reviewed the thoracic and lumbar spine radiographs of 54 more
      adult patients with sickle cell anemia. RESULTS AND CONCLUSION: A total of eight
      patients (14%) displayed infarcted vertebrae with compensatory vertical growth of
      at least one adjacent vertebrae. These resemble the elongated vertebral bodies
      associated with other conditions. We can find no prior report of this finding in
      association with sickle cell anemia.

PMID- 9592902
TI  - Magnetic resonance imaging: a cost-effective alternative to bone scintigraphy in
      the evaluation of patients with suspected hip fractures.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of magnetic resonance imaging (MRI)
      compared with radionuclide bone scan in the evaluation of patients with
      clinically suspected hip fractures. DESIGN: The medical records of all patients
      who had been seen in the emergency room over a 4 1/2 year period with a
      clinically suspected hip fracture, negative or equivocal plain films, and either
      a subsequent bone scan or MRI examination were retrospectively reviewed. The time
      to diagnosis, admission rate, and time to surgery were determined. A two-sample t
      test was used to assess the statistical significance of the results. A
      theoretical cost analysis was performed using current charges to estimate all
      expenses. PATIENTS: Forty patients (11 male, 29 female; age 28-99 years)
      satisfied our inclusion criteria. RESULTS AND CONCLUSIONS: Twenty-one patients
      had bone scans (six with fractures), and 19 had MRI (four with fractures). The
      time to diagnosis was 2.24 +/- 1.30 days for bone scanning and 0.368 +/- 0.597
      days for MRI (P < 0.0001). Twenty patients in the bone scan group were admitted
      compared with 13 in the MRI group. The time to surgery was at least 1 day longer
      in patients undergoing bone scanning. Bone scanning resulted in higher patient
      costs compared with MRI because of the delay in diagnosis. In the evaluation of
      patients with suspected hip fractures, early MRI is more cost-effective than
      delayed bone scanning. Further prospective studies comparing the cost
      effectiveness of early MRI with early bone scanning are needed.

PMID- 9592903
TI  - Regional bone changes in deep soft tissue hemangiomas: radiographic and MR
      features.
AB  - OBJECTIVE: To evaluate changes in bone adjacent to deep soft tissue hemangiomas
      of the extremities. DESIGN AND PATIENTS: We retrospectively reviewed the plain
      films of 115 patients with histologically proven deep soft tissue hemangiomas of
      the extremities. The length and pattern of the bone changes were analyzed and
      correlated with the MRI examination (n = 55) and surgical findings. RESULTS:
      Plain film studies demonstrated reactive bone changes adjacent to the deep soft
      tissue hemangiomas in 24 (21%) patients and phleboliths in 23 (20%) patients. The
      results of plain film analysis revealed a wide spectrum of regional bone changes
      adjacent to the hemangiomas, including periosteal reactions (16%), regional
      osteopenia (1%), cortical erosion (3%), bony overgrowth (3%), coarsening of the
      trabeculae (5%), and a combination of the above changes (4%). The length of the
      reactive changes corresponded approximately to the size of the hemangioma in 70%
      and was longer than the largest dimension of the hemangioma in 30%. Of the 55
      patients studied with MRI, 39 (71%) patients had normal bones and 16 (29%) had
      bone changes. CONCLUSION: Deep soft tissue hemangiomas may cause changes in
      adjacent bones. Familiarity with the pattern of reactive bone changes may help to
      avoid misdiagnosis.

PMID- 9592904
TI  - Granuloma annulare: radiographic demonstration of progressive mutilating
      arthropathy with vanishing bones.
AB  - Granuloma annulare, a relatively common cutaneous disorder of unknown origin, is
      named for its predominantly papular lesions, which tend to group and coalesce in
      an annular fashion. Clinically distinct subtypes are divided into localized,
      generalized, perforating, and subcutaneous forms. Only the superficial
      granulomata of the extremities in subcutaneous granuloma annulare have been
      radiographically depicted in the literature. We describe and illustrate what we
      believe is the first radiographic presentation of bone and joint involvement with
      advanced, generalized granuloma annulare.

PMID- 9592905
TI  - Subcutaneous granuloma annulare: MR imaging findings.
AB  - We present a case of subcutaneous granuloma annulare evaluated with MR imaging.
      The mass was poorly defined and showed thickened interconnecting strands with low
      signal intensity on T1- and T2-weighted MR images. When a poorly defined
      subcutaneous mass with low signal intensity on both T1- and T2-weighted MR images
      is observed in an otherwise healthy child, subcutaneous granuloma annulare should
      receive serious consideration. Subcutaneous granuloma annulare should be added to
      the list of tumors with short T2.

PMID- 9592906
TI  - MR imaging of ulnar nerve entrapment secondary to an anomalous wrist muscle.
AB  - MR imaging of an anomalous hypothenar adductor muscle causing isolated deep ulnar
      nerve branch compression and producing a purely motor neuropathy is presented.
      The muscle appears to represent a type 1 variant of the intrinsic anomalous
      hypothenar adductor muscle.

PMID- 9592907
TI  - Low incorporation of soleus tendon: a potential diagnostic pitfall on MR imaging.
AB  - We describe a case of thickening and longitudinal increased signal within the
      Achilles tendon in a patient denying any recent or previous history of Achilles
      tendon injury. The MR appearance, while simulating tendinosis or rupture, was
      compatible with incomplete incorporation of the soleus tendon into the
      gastrocnemius tendon. This constitutes a normal anatomical variant, not
      previously described in the radiologic literature, and should not be confused
      with increased signal and thickening due to disease of the Achilles tendon.

PMID- 9592908
TI  - Tunneling Schmorl's nodes.

PMID- 9592909
TI  - Intracortical osteosarcoma.
AB  - Intracortical osteosarcomas originate in the bone cortex and represent the rarest
      type of osteosarcoma. We describe the clinical, radiological and histological
      features of an intracortical osteosarcoma occurring in the femur of a young man
      and discuss the pertinent features of this tumour compared to those previously
      reported.

PMID- 9592910
TI  - Multicentric malignant transformation of multiple exostoses.
AB  - We treated a patient with large multiple chondrosarcomas derived from multiple
      cartilaginous exostoses. One sarcoma originated in the left pubic bone and the
      other sarcoma in the posterior aspect of the greater trochanter of the left
      femur. Thirty months after hindquarter amputation, the patient is alive without
      relapse. This is the first report of a patient with synchronous multiple
      malignant transformation of multiple cartilaginous exostoses.

PMID- 9592911
TI  - [Energy requirement for the crawl and backstroke in free competition].

PMID- 9592912
TI  - [Functional neuroanatomy of the radial nerve in the region of the long wrist and
      finger joint extensors and the supinator groove].
AB  - Basing on electrophysiological data measured by us we studied the course of the
      radial nerve or its motoric branches with regard to anatomically conditioned bony
      contractions and their possible significance for pain experienced at the radial
      epicondyle of humerus, the pain being known under several synonymous
      designations. To differentiate between the various pathomechanisms discussed in
      the literature, we performed longitudinal and transversal dissections on a total
      of 40 cadaveric arms. We found as constant variations to the topographic anatomy
      published in the standard literature a regularly extended and (in relation to the
      other muscles we examined) exposed course of the nerve branch proceeding towards
      the m. extensor carpi radialis brevis. As the only long wrist extensor muscle
      this is innervated in most cases from the superficial end branch of the radial
      nerve. The origin of the muscle projected regularly over the common aponeurosis
      of the extensor tendon and delimitated in most of the preparations the distal end
      of the tunnel of the deep radial nerve. Since the deep radial branch and the
      muscular branches parallel to that branch cross this part of the tendon at an
      obtuse angle we believe that the repeatedly discussed possibility of a dynamic
      nerve compression without structural influences is the triggering mechanism for
      the observed nerve damage.

PMID- 9592913
TI  - [Neurophysiologic findings in radio-humeral epicondyle pathology].
AB  - A number of authors assumed a compression syndrome of the radial nerve or its
      branches to be responsible for the heterogenous classified picture of
      radiohumeral epicondylopathy. Various structural and functional stenoses have
      been discussed as possible causes. We performed electromyographies on the
      extensor muscles, subdividing from the radial epicondyle and found significant (p
      < 0.05) changes in 27/51 patients regarding latency, velocity of neural
      conduction and rate of polyphasic potentials. Especially affected were the
      extensor carpi radialis brevis and extensor digitorum muscle. These findings were
      confirmed by torque measurements and histologic observations from both muscular
      and tendon biopsies. In summary, we believe the model of a neurogenous origin of
      radio-humeral epicondylopathy to be an appropriate explanation.

PMID- 9592914
TI  - [The influence of knee bandages on sport specific capabilities in healthy
      volunteers and patients with rupture of the anterior cruciate ligament].
AB  - In 15 male healthy volunteers and 10 male patients with ACL-deficiency sports
      specific capabilities were evaluated with a 9-3-6-3-9-run and a single-leg
      jumping test. Each subject was tested with and without different knee bandages.
      We evaluated the Patelladyn-, the Kasseler-, the Super-Genuplus-, and the Genuhit
      bandage. Additionally a subjective assessment of each bandage was performed by
      the volunteers. There were no significant difference performing the 9-3-6-3-9-run
      between all of the bandages in the control-group. Comparing the injured group
      with the control there were significant differences. All bandages led to
      improvement without reaching the running time, which was used by the controls.
      Performing the single leg jumping test there were also no differences with the
      different bandages in the healthy control group. However, after applying a
      bandage in the injured subjects, the time improved significantly. In the
      subjective assessment the Patelladyn-bandage scored best.

PMID- 9592915
TI  - [Acute and chronic overuse injuries in extreme sport-climbing].
AB  - From May to September 1994 a study on acute and chronic overuse injuries in to
      rockclimbing was performed. The etiology of trauma was referred to trainingforms
      and climbing techniques. 112 climbers participating in the study climbed at level
      9+/10- (8a). This study demonstrated that the incidence of overstrain syndromes
      increased with the performance level. The overall predominance of finger injuries
      was followed by acute spinal syndromes, knee, and ankle sprains. Among the most
      frequent overstrain complaints epicondylopathias, chronic complaints of the
      finger joins and flexor tendons, and nerve compression syndromes of the upper
      extremities could be seen. Most notable was the fact that the frequency of
      certain overstrain syndromes increased in relation to the years of climbing.

PMID- 9592916
TI  - [Injury risk of competitive, handicapped cross-country skiers in training nd
      competition].
AB  - Injuries caused by cross country skiing have been poorly investigated in
      handicapped athletes. The dynamic sliding shape of motion makes this sport to a
      suitable discipline for people with a deficit of locomotion. Visual handicapped
      people with a guide are able to improve their motoric skills, co-ordination,
      orientation and body self-consciousness in the track. Since handicapped athletes
      are performing in international competitions the training intensity to fulfill
      the requirements, but also the risk of overstrain induced injuries got increased,
      like in other high-performance sports. Our study examined injuries and overuse
      syndromes of the German National Team Ski Nordic during the Paralympics in
      Tignes/ Albertville (1992). Lillehammer (1994) and the training period in
      preparation for the Paralympics in Nagano (March 1998). The incidence and kind of
      injuries in the competitive handicapped cross country skier was comparable with
      non-handicapped athletes, but the injury pattern was different.

PMID- 9592917
TI  - [Injury profile in school sports. A sports medicine analysis in an annual report
      on schools].
AB  - A current injury profile was constructed on the data of the accident reports (n =
      6366) in school sport coming in with the municipality accident insurance
      association for Schleswig-Holstein. The largest injury frequency occurred at the
      period from 9 o'clock until 10 o'clock. In this way, the "2nd hour" showed the
      highest injury risk referring to the lessons. In this case, a significant
      connection appeared between motivation and injury risk. The upper extremities
      were affected with a part of about 48% of all injuries most frequently. Within
      the injury kinds the distortion in 45% of the cases dominated. Cause of the
      injuries was the ball in 28% of the cases. The most injuries within the ball
      games resulted at the basketball (17%). By far most injuries of upper extremities
      occurred during a game phase. In about 80% the cases the injuries were on the
      fingers identified caused by the ball. The present results can help to analyze
      causes of accident and discuss measures for the prevention of sport injuries
      during the school sport.

PMID- 9592918
TI  - [Stress fractures of the femoral neck due to step aerobics--case report].
AB  - With the rising public interest in physical fitness an increasing number of
      stress reactions of the bone are diagnosed. Commonly known in competitive
      athletes, they are increasingly seen in recreational sports. Stress reactions of
      the bone are a disorder between the loading force and the capability to
      compensate. Stress fractures with displacement of the bone are more rarely
      diagnosed due to improved diagnostic means. Stress fractures of the medial
      femoral neck in young athletes are uncommon. We are reporting the case of a
      beginning tension type stress fracture of the medial femoral neck of a 29 year
      old female recreational athlete after excessive stepping and step aerobic at a
      fitness center.

PMID- 9592919
TI  - [Traumatology of volleyball in adolescents and children].

PMID- 9592920
TI  - [Sudden sports deaths in the armed forces of Germany].
AB  - All Soldiers are obliged to participate in sports educational programs of the
      services, with the exception of severe restrictions due to individual health
      problems. During sports activities from 1/1989 to 12/1995 7 soldiers died, 3
      (i.e. 43%) during soccer games. Based on a troops strength of 370,000 men, we
      found a yearly incidence of 0.27 sports deaths/100,000 soldiers. This result
      correlates with the incidence of sports deaths of club athletes in the greatest
      European sports death study.

PMID- 9592921
TI  - [Medical aspects of selecting a new high performance olympic sail boat].
AB  - For the 2000 Olympic Sailing-Regatta the Medical Commission of the International
      Sailing Federation (ISAF) analysed different high performance dinghy boats from
      the medical point of view. The hull of the boats and the modern styled sails
      increase the forward force. Special outriggers compensate the shearing forces, by
      which different weights of the sailors make no longer a difference in case of
      moderate winds. The high distance between boat and boom is favorable to prevent
      head injuries. But in some boats many clips, rollers, ropes, hooks are installed
      in those areas, where the helmsman and the foredeck hand are active. The area
      between the outrigger tube should be covered with fabric being pervious to water:
      in case of a sailor's slip off or an overturn of the boat no part of the body can
      be squeezed. The foot straps mostly enclose the metatarsus: At manoeuvres or
      capzising a foot-fracture could happen. The selected boat for the Olympic Games
      was the 49er.

PMID- 9592922
TI  - Nursing homes--structure and selected characteristics, 1987 and 1996.
AB  - This paper briefly describes changes in the nursing home market over a nine-year
      period, 1987 to 1996. Estimates are based on the "Institutional Population
      Component" of the 1987 National Medical Expenditure Survey (NMES) and the
      "Nursing Home Component" of the 1996 Medical Expenditure Panel Survey (MEPS).
      Both surveys were sponsored by the Agency for Health Care Policy and Research. On
      January 1, 1996, approximately 1.56 million residents were receiving care in
      16,840 nursing homes with 1.76 million beds. This compares to 1.36 million
      residents in 14,050 nursing homes with 1.48 million beds in 1987, increases of
      15, 20 and 19 percent, respectively. The average size of a nursing home remained
      constant. The occupancy rate decreased from 92 percent in 1987 to 89 percent in
      1996, in spite of the growth of the elderly population, both in relative and
      absolute terms. There was also a significant drop in the supply of nursing home
      beds relative to the elderly population; this decrease was observed in all four
      regions of the country, with the greatest drop being in the West. In 1987 only 28
      percent of nursing homes were certified by both Medicare and Medicaid (dually
      certified), while this proportion increased to 73 percent in 1996. Conversely,
      while only 17 percent of nursing homes were certified by only Medicaid in 1996, a
      full 50 percent were certified as such in 1987. By far the most common type of
      nursing home in both 1987 and 1996 was the nursing home with only nursing home
      beds. Such nursing homes represented 87 percent of the market in 1987 but just 77
      percent in 1996. The remaining were either hospital-based or nursing homes with
      personal care and/or independent living beds in addition to nursing home beds or
      were part of a continuing care retirement community.

PMID- 9592923
TI  - Fatal falls: trends and characteristics.
AB  - Falls accounted for more than 14,000 deaths and 22 million visits to hospitals
      and physicians' offices in 1996. They are the second leading cause of
      unintentional-injury death for people of all ages and the leading cause for
      people 79 years old and older. Fall death rates increase steadily with age and
      the death rate for men is always greater than the rate for women. Homes and
      resident institutions are the two most commonly named places where fatal falls
      occur. Fall death rates by state show no particular geographical patterns. There
      has been a significant decline in both numbers of deaths and death rates due to
      falls over the past 50 years. The improvement in the death rate has been achieved
      in all age groups. From 1948 to 1996, the death rate in each age group decreased
      between 61 percent and 80 percent. The change is most evident in the 65 and older
      age group, whose rate dropped from 136.8 per 100,000 persons to 33.1. Possible
      reasons for the decline in death rates include specific programs, such as
      "Children Can't Fly," and workplace fall protection programs; general factors
      such as improved acute care, rehabilitation and nutrition, as well as long-term
      changes in environmental factors such as design of and materials for stairs,
      steps and handrails; improved materials for shoe soles; and improved floor
      finishes and floor coverings.

PMID- 9592924
TI  - Individuals with COBRA coverage, 1994-1995. Consolidated Omnibus Budget
      Reconciliation Act.
AB  - COBRA (Consolidated Omnibus Budget Reconciliation Act of 1985) coverage can be
      considered advantageous for most workers. Although an employee can be required to
      pay 102 percent of the premium for COBRA coverage, workers can usually realize
      significant savings compared to purchasing the equivalent health insurance policy
      in the private market. Many employers consider COBRA to be a costly mandate for
      three reasons. First, premiums collected from COBRA beneficiaries typically do
      not cover the costs of the health care services rendered. Second, COBRA imposes
      an additional administrative cost on employers. Third, many employers view the
      penalties for noncompliance as excessively large. We examined data from the 1993
      panel of the Survey of Income and Program Participation (SIPP) to gain a better
      understanding of the COBRA population. The COBRA population was found to be much
      older than the population of individuals with employment-based coverage through
      their current employer. COBRA beneficiaries were also more likely than
      individuals with coverage through a current employer to be male, married, white
      and to have a graduate school education. They were also less likely to be working
      and were more likely to have retirement income. Any attempt to expand COBRA
      coverage, either through subsidies or by allowing workers to choose from plans
      with lower premiums, will likely result in increased employer health care costs.
      Survey data indicate that the primary issue concerning COBRA is its impact on
      claims experience and administrative costs on active employees, employers and
      COBRA beneficiaries. If the cost issues are not addressed with future COBRA
      expansions, employers may consider various alternatives to reduce, shift or
      eliminate the impact of this increased cost.

PMID- 9592925
TI  - Variations in charges for two major breast cancer surgeries, United States, 1996.
AB  - In 1996 the total in-hospital charges for the primary treatment of breast cancer
      with a modified radical mastectomy averaged $10,000 throughout the United States.
      The total charge (hospital plus physician's fees) varied by 95 percent between
      the high charge reported in New York ($12,690) and the low charge in Michigan
      ($6,510). The hospital portion of the bill averaged 65 percent of the total and
      ranged from 51 percent in New York to 74 percent in Virginia. The average length
      of stay for these women was 2.39 days and ranged from 3.18 days in New York to
      1.69 and 1.66 days in Washington and Arizona, respectively. The average charge
      for a partial mastectomy was $8,760 with notable variations between states. The
      Texas total charge was the highest ($12,890, some 47 percent above the U.S. norm)
      and more than twice the low charge in Ohio ($6,080, 31 percent below the U.S.
      average). The physicians' charges averaged $3,330 for the country as a whole and
      accounted for 38 percent of the bill. This proportion ranged from 46 percent of
      the total in New York to 70 percent in Indiana and Colorado. The average length
      of hospitalization for a partial mastectomy was 1.84 days. On average, women
      remained in the hospital for the longest time in New Jersey (2.78 days) and for
      the shortest time in Oregon and Massachusetts (1.40 days and 1.45 days,
      respectively).

PMID- 9592927
TI  - [Several aspects of modern literature research].
AB  - This article reviews today's methods of searching the literature, especially the
      electronic ones. There are 2 main methods of searching: CD-ROM- and online
      searching. Online searching is a fast and powerful alternative to CD-ROM
      searching. Formal training is necessary for quick and cheap reference finding.
      Other benefits such as direct transfer from online searching to your own computer
      bibliography database make online searching of biomedical databases essential to
      consider.

PMID- 9592926
TI  - [Organ transplantation: humanitarian--legal--ethical].
AB  - Thorough examinations and discussions made clear: brain-death must be identical
      with the total death of the individual person. This must be the basis for legal
      organ transplantation. However--as men always tend to make bad things out of good
      -there exists criminal organ trade, including murder on order. Serious medicine
      as well as the serious patient must keep complete distance to these malpractices,
      even regarding that there are scarcity of organs for transplantation and long
      waiting lists. Different countries have different legistic regulations. Austria
      is envied by many others for its legal regulations.

PMID- 9592928
TI  - [Neurological problems in environmental medicine].
AB  - It has been tried to demonstrate the role of neurology in the new medical
      discipline "environmental medicine" or "clinical ecology". Encephalopathy and
      polyneuropathy are the most common diseases related to neurology following the
      exposure to low levels of environmental substances. The problems of measuring are
      discussed, also the difference to other causes of illness. Important are also
      psychological aspects in the whole context of environmental medicine. The
      importance of amalgam, organic solvents and ozone is explained in their relation
      to neurology and clinical ecology. Mentioned is also the difficult concept of
      "multiple chemical sensitivity". Referring to the environmental consultation an
      open and evaluating attitude is recommended to avoid damage as a result of
      environmental poisoning equally to exaggerated medical activities.

PMID- 9592929
TI  - [Vienna standard in diagnosis of nicotine dependence: Vienna Standard Smoking
      Inventory].
AB  - The Standard Vienna Smokers' Inventory (VSSI) ("Wiener Standard Raucher-Inventar"
      [WSR]) is based on the authors' experience and was designed to optimize primary
      and additional diagnostic procedures associated with smoking cessation treatment.
      The aim of this inventory is to enable therapists interested in smoking cessation
      interventions to initiate diagnostic procedures as well as to use efficient
      therapeutic modalities. The study also highlights those areas of the patient's
      history which should be given special attention and the theoretical background of
      these areas. The various comprehensive sections of the WSR include general data
      pertaining to the patient's life, the basic situation (basic rate), especially
      with regard to nicotine dependence, pre-abstinence syndrome and "tar" exposition
      values, follow-up of smoking habits, earlier attempts to give up smoking, and
      possible barriers to cessation of smoking--such as insufficient motivation,
      "nocturnal sleep disturbing nicotine craving" or carbohydrate dependence.
      Furthermore, previous illnesses, pre-existing risk factors and regular intake of
      drugs are also discussed. Finally, the study emphasizes that the WSR should be
      used by the therapist according to his/her level of training and experience, thus
      providing the possibility to use specific, individual approaches to deal with
      specific individuals and situations.

PMID- 9592930
TI  - [Application of theoretical and synthetic models to cytochrome P450 catalysed
      metabolic reactions].
AB  - In addition to in vivo and in vitro methods, models of structural and theoretical
      biochemistry as well as bioorganic studies were found to be useful for
      understanding metabolic activity on a molecular basis. Metabolism of an AChE
      inhibitor, carbofuran was studied. Product selectivity observed in vitro and in
      vivo was explained by theoretical methods. Metabolic profiles can be reproduced
      using P450 mimic synthetic porphyrins. Insight into the mechanism of metabolic
      reactions might be applied for the identification of metabolically sensitive
      substructures as well as for the prediction of metabolic profiles.

PMID- 9592931
TI  - [3D QSAR analysis of novel 5-HT1A receptor ligands].
AB  - In an effort to develop a quantitative ligand-binding model for 5-HT1A receptors,
      a pharmacophore mapping procedure, DIStance COmparison (DISCO) was used to
      identify structural features that are common in a novel set of
      pyridazinothiazepines and pyridazinooxazepines with moderate-to high affinity to
      5-HT1A-receptors. The pharmacophore thus obtained provided a good starting point
      for a Comparative Molecular Field Analysis (CoMFA) study. The CoMFA gave
      acceptable statistical measure (R2CV = 0.52 by using six latent variables,
      whereas it afforded a non cross-validated R2 value of 1.00). Predictability of
      our model was tested by a separated prediction set of four compounds, for them
      the relative deviations between calculated and measured biological activity
      values did not exceed 10%.

PMID- 9592932
TI  - [Interesting new rearrangements of the cephalosporin antibiotics].
AB  - On the course of the preparation of new cephalosporin derivatives with potential
      HLE inhibiting activity, three new rearrangements were observed. When a 7 beta
      aminocephem sulfone (prepared in situ from 2) was diazotized in methanolic HClO4
      solution with HNO2, the triazole 3 was prepared in good yield. On the other hand,
      the 2 alpha-bromocephem 6 rearranged to two different products, depending on the
      solvent used. When it was allowed to stay in acetonitrile for 7 days, the
      bromopyrrol 8 was the product, while in acetone, THF or DMF the aromatic side
      chain brominated product 7 was obtained. In both cases the inverse polarity of
      the C-2-Br bond and the easily resulting bromonium ion can be regarded
      responsible for the rearrangements.

PMID- 9592933
TI  - [New antitumor derivatives of vinblastine].
AB  - The alkaloids of Catharanthus roseus vincristine 1 and vinblastine 2 are widely
      used in the chemotherapy of cancer. Their nitro-derivatives have also antitumour
      activity [2]. The dinitro-derivatives 4, 6-9 were prepared for pharmacological
      investigation. Some new hydroxymethyl derivatives 12-14, 17-18, 23-24 of the
      antitumour indole-indoline alkaloids vinblastine 2 and leurosine 5 were
      synthetised in two different ways a) by the selective reduction of 2, 5 or
      deacetoxy-vinblastine 16, b) by the ferric chloride mediated coupling reaction of
      catharanthine 19 and the corresponding vindoline derivatives 21, 22. Synthetising
      24 a new bisvindoline 25 was the main product. 13 and 14 showed cytotoxic
      activity for small cell lung cancer LXFS 650.

PMID- 9592935
TI  - [Optimization of bioavailability of pharmacons].
AB  - The authors have investigated the optimization possibilities of bioavailability
      of drugs as spray-drying, spray-embedding, spray-freezing, inclusion complex
      formation with cyclodextrin derivatives, mineral complex formation with bentonite
      and in vitro diffusion of products. The bioavailability of drugs may be
      significantly influenced with these methods.

PMID- 9592934
TI  - [Estimation of the binding site of drugs by means of new types of photoactive
      ligands].
AB  - Photoaffinity labeling is a powerful technique to identify ligand-binding
      proteins in a crude mixture and localize their binding-site. Benzophenone
      photophore has several favorable features compared with the classical
      photoreactive unit, aromatic azides, that is why its application is expanding.
      Benzophenone can easily be attached to biologically active ligands by using a
      tritiated heterobifunctional crosslinker reagent: [3H]-BZDC-NHS or a
      photoreactive amino acid; [3H]-4-benzoyl-L-phenylalanine. Tethered inositol
      polyphosphates and antimitotic agents were prepared first and reacted with the
      high specific activity photocrosslinker reagent in microscale. The
      photoactivatable ligands obtained were used for studying IP3 receptor, alpha
      Trinozitol receptor, PLC delta enzime, beta-tubullin and glycoprotein P. Thrombin
      receptor was investigated by a short peptide antagonist containing the
      photoactivatable amino acid. The results demonstrate the versatility of
      photoaffinity labeling and prove that this technique has a potential providing
      much more information about the receptor and mechanism than simply identifying a
      single polypeptide: it contributed to solve the 3D structure of the IP3 binding
      domain and to reveal a unique activation of the PLC delta. The results confirmed
      the superiority of benzophenone. Using that photophore glycoprotein P, which is
      responsible for the MDR, and thrombin receptor were labelled at the first time.

PMID- 9592936
TI  - [Spherical crystallization in pharmaceutical technology].
AB  - Physical properties of crystals, such as size, crystal size distribution and
      morphology, may predetermine the usefulness of crystalline materials in many
      pharmaceutical application. The above properties can be regulated with the
      crystallization process. The spherical crystals are suitable for direct tablet
      making because of their better flowability and compressibility properties. These
      crystals can be used in the filling of the capsule. In this work, the spherical
      crystals such as "single crystal", "poly-crystals" and agglomerates with other
      excipients are collected from the literature and the experimental results of the
      authors. A close cooperation between chemists and the pharmaceutical
      technologists can help for doing steps in this field.

PMID- 9592937
TI  - [Nebulized drug aerosol systems].
AB  - To ensure the pulmonary absorption of medicines a developing technologist may
      choose from among several alternative possibilities. In the medical practice
      sprays made by mechanical spraying are of great importance. In this study
      depositions of fine mists made by OMRON ultrasonic nebulizer in Kirk Model
      apparatus were investigated. The absorption of sodium chloride (0.9% w/v) and
      theophylline (0.108 w/v) were monitored by chloride selective electrode and UV
      spectrophotometry, respectively. The aim of the study was to investigate how the
      nebulizer influences the deposition of medical mists. The results show that
      appropriate mist and ventillation produced by the OMRON nebulizer ensure the
      absorption of the medicines in the lung.

PMID- 9592938
TI  - [Evaluation of substrate-binder interfacial interactions].
AB  - Substrate-binder interfacial interactions were evaluated on the basis of the
      physico-chemical and mechanical properties of granules and compressed samples.
      Linear relationship was found between the breaking strength, the diffuse
      reflectance and the binder content of the examined granule-systems and compressed
      samples. The increasing amount of binder in the granules improved the adhesive
      interaction existing between the substrate and the binder. Our results indicate
      that the mechanical properties of the single particles as well as of the
      compressed samples were basically determined by the physico-chemical interactions
      of the substrate-binder interfacial layer. The qualitative and quantitative
      evaluation of these interactions has a decisive impact on the formulation and in
      process control of solid dosage forms of optimal mechanical properties.

PMID- 9592939
TI  - [Filtration of solutions with high viscosity: from laboratory experiments to
      production].
AB  - The Zinc Hyaluronate complex has several advantages from the point of view of
      woundhealing. The author's task was the elaboration of the sterile filtration
      technology of the 0.2% Zinc Hyaluronate solution. In the first step 0.2 micron
      pore diameter filters were used. During the scale up process we found that the
      filter boards are not suitable. The filtration time extremely increased and
      sometimes the whole process stopped because of the relatively small filtration
      area. For larger batches polypropylene capsule filters have been applied. The
      mean pore diameter of the filter was 0.2 micron but the unregular pore size
      distribution did not make the filtrate microbe free. In the next experience inlet
      pore diameter was 0.65 micron--the outlet pore diameter 0.45 micron. This
      filtration process resulted in a sterile filtrate with reduced active content.
      This means that the solution has been ultrafiltrated. Applying too high pressure
      and form a compact layer on the filter's surface which is functioning as a
      secondary filter layer. The filtration should begin with low pressure and it has
      to increase it gradually from 0 to 2 bar in 0.5 bar steps. It was supposed that
      at high temperature filtration could be easier and faster. On the contrary we
      found that depending on the concentration above 35-45 degrees C the active
      content of the filtrate is decreasing. In the case of the filtration of the
      fraction with a lower temperature the fractions with high molecular weight can be
      filtrated because of the anisometric distribution of the molecules. The
      filtration of these products is very difficult even at laboratory scale.

PMID- 9592940
TI  - [Influence of different auxiliary materials on the dissolution of carbamazepine
      from solid dosage forms].
AB  - Results of the development of a solid dosage form containing 200 mg Carbamazepine
      (CBZ) are presented. Citric acid and low substituted Hydroxypropyl-cellulose (L
      HPC) were used as dissolution enhancers of the active ingredient. Granulation the
      CBZ and citric acid with water has no effect on the dissolution of CBZ, but the
      granulation with absolute alcohol increases the dissolution rate. This
      enhancement could be explained with a molecular interaction between the CBZ and
      citric acid in water-free media. This interaction is indicated by the melting
      points, IR-spectra and scanning electron microscopy of the materials and
      granules. Further dissolution enhancement can be reached with L-HPC because of
      its disintegrating effect on the granules. Application of citric acid and L-HPC
      together results in extremely fast dissolution of the CBZ.

PMID- 9592941
TI  - Disease occurrence and risk factor analysis in Finnish Ayrshire cows.
AB  - Disease occurrences and risk factors for the most common diseases among 39,727
      Finnish Ayrshire dairy cows belonging to 2338 herds were studied. All the cows
      calved during 1993 and were followed until the next calving or culling.
      Lactational incidence risks, recurrence of, and number of treatments required for
      one episode of a disease are described for 17 different veterinary diagnoses. The
      5 most common diseases and their lactational incidence risks were: acute mastitis
      (17.0%), anestrus (8.1%), ovarian cysts (7.3%), milk fever (5.4%), and ketosis
      (4.9%). The highest recurrence probability (14.2%) was observed for acute
      mastitis, followed by fertility disorders. Milk fever was the one disease that
      required the most repeated treatments, i.e., almost 30% of the cows were treated
      at least twice, whereas for most of the other diseases about 10% of the cows
      required more than one treatment per first episode of the disease. Logistic
      regression models were fitted to study the effect of milk yield and other risk
      factors on the occurrence of the 5 most common diseases. Increasing milk yield
      was found to be a risk factor for acute mastitis, ovarian cysts, and for anestrus
      among older cows (parity > 2), and for milk fever among younger cows (parity =
      2). Several diseases were found to be risk factors for other diseases.

PMID- 9592942
TI  - Arthroscopic removal of palmar/plantar osteochondral fragments (POF) in the
      metacarpo- and metatarso-phalangeal joints of standardbred trotters--outcome and
      possible genetic background to POF.
AB  - A clinical material of 133 Standardbred horses with palmar/plantar osteochondral
      fragments (POF) in the metacarpo- and metatarsophalangeal joints were studied.
      All horses had their fragments removed with arthroscopic surgery. 102 of the
      horses were 3 years old or younger when surgery was performed. Anatomical
      localisations of the fragments were in agreement with earlier reports. There was
      no statistical significant difference in month of birth in the POF--group
      compared to the total population. Eighty % of the horses that had raced before
      surgery came back to racing. The racing performance relative to their
      contemporaries remained the same after the POF operation. 65% of the horses that
      had not raced before surgery raced after the operation. The breeding index BLUP
      (Best Linear Unbiased Prediction) was used to evaluate if the POF-horses differed
      genetically in racing ability from the total population. The average BLUP value
      of the POF group was 103.4 (+/- 0.65), while the mean BLUP value of the total
      population was 98.9. This difference was highly significant and indicated that
      these POF horses belonged to a selected group. A homogeneity test of allele
      frequencies in blood type systems was performed to evaluate if any genetic
      difference was persistent between POF horses compared to the total population.
      The statistical analysis of gene frequencies for alleles in blood type systems
      indicated a genetic discrimination in blood type systems D and Tf.

PMID- 9592943
TI  - Temporary suppression of cell-mediated immunity in standardbred horses with
      decreased athletic capacity.
AB  - Eighty Standardbred horses, originating from 5 training campuses, with decreased
      athletic performance in association with symptoms such as intermittent fever and
      mild pharyngitis were examined. As control animals, 10 horses from a stable with
      normally performing horses were used. Virus isolation and clinico-chemical and
      serological tests were performed. Lymphocyte proliferation tests were carried out
      to evaluate the capacity of the cell-mediated immunity. In addition, a bioassay
      for equine type I interferon, as a marker for early viral infections, was
      established. No specific microbe could be linked to these symptoms, but there was
      a temporary suppression of the cell-mediated immunity, which might be explained
      by the serological evidence of an EHV-2 and/or rhinovirus infection.

PMID- 9592945
TI  - Relationships between selected climatic factors in fattening units and their
      influence on the development of respiratory diseases in swine.
AB  - The correlation between climatic parameters with one another in fattening units
      and the influence of environmental factors on lung lesions registered at
      slaughter were studied in 6 integrated herds with continuous production systems.
      In addition, the influence of environmental parameters on the spread of
      Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae (serotypes 2 and 3)
      and on the productivity was monitored in 2 specialized fattening herds with
      strict batch production. The outdoor temperature was positively correlated to the
      indoor temperature, but negatively correlated to the relative humidity and the
      concentration of carbon dioxide in the stables. These indoor parameters were also
      correlated to each other. The concentration of ammonia was not correlated to any
      other climatic parameter. No correlation between the climatic parameters measured
      and the prevalences of pneumonia and pleuritis registered at slaughter was shown.
      The rapidness in spread of mycoplasmosis seemed to be more dependent of the
      antibody status of the pigs on arrival than on the climate of the units. In
      contrast, a correlation between the climatic parameters and the spread of the
      less contagious infection (Actinobacillus) was indicated. The influence of the
      climatic parameters on the daily weight gain was not ensured.

PMID- 9592944
TI  - Seasonal variation in live weight, testes size, testosterone, LH secretion,
      melatonin and thyroxine in Merino and Corriedale rams in a subtropical climate.
AB  - In the present investigation we studied the seasonal changes in live weight and
      testes and pituitary activity in Merino and Corriedale rams in a subtropical
      climate. Testes activity was measured as scrotal circumference (SC), plasma
      concentration of testosterone (T) and release of testosterone after exogenous
      GnRH injection. LH pulsatility and pituitary LH responsiveness to exogenous GnRH
      was measured as an index of pituitary activity. In addition, we wanted to
      characterize the seasonal pattern of thyroxine (T4) secretion and the 24 h
      secretory pattern of melatonin (M) at the winter and summer solstices in the 2
      breeds. Nine Corriedale and 7 Merino adult (4-6 years) rams were kept on native
      pasture and managed in one group. Twice a month live weight (LW) and scrotal
      circumference (SC) were measured. To monitor plasma concentration of testosterone
      (T), and thyroxine (T4), 5 animals of each breed were bled every month except
      during autumn (March-May), when blood samples were collected with 15 day
      intervals and in spring (October) with 10 day intervals. To monitor pulsatile LH
      secretion, 3 rams of each breed were bled at 15 min intervals for 6 h at the
      winter and summer solstices and spring and autumn equinoxes. Pituitary LH and
      testicular testosterone response to GnRH injection was performed bimonthly from 2
      animals of each breed. No effect of breed was found on any of the variables
      investigated. An interaction between breed and sampling date was found in LW (p <
      0.001) and total T response after GnRH challenge (p < 0.001). Sampling date had a
      significant effect (p < 0.001) on all the variables studied. In both breeds SC
      decreased during autumn and increased during spring with minimum T concentrations
      in late autumn and maximum in mid-summer/early autumn. The lowest (p < 0.05)
      number of LH pulses were observed in winter (June) and the highest (p < 0.05) in
      early autumn (March). The highest LH and testosterone response to GnRH challenge
      was observed in autumn (April) (p < 0.05) in both breeds. Baseline concentrations
      of M were similar in both breeds at the winter and summer solstices and high
      concentrations were observed during the dark period on both occasions. In both
      breeds thyroxine was high at the end of winter/spring (February-April) and low
      from the end of summer to mid-autumn (August-November). The results show that
      Corriedale and Merino rams under subtropical conditions have annual reproductive
      cycles. There was an association (p < 0.001) between changes in LW and SC in the
      2 breeds and this relationship was stronger in Merino rams (R2 = 0.68) than in
      Corriedale (R2 = 0.33) which indicates that nutritional factors may have more
      influence on the reproductive cycle of Merino than Corriedale rams.

PMID- 9592947
TI  - Plasma levels of progesterone and cortisol after ACTH administration in lactating
      primiparous sows.
AB  - The effect of adrenocorticotropic hormone (ACTH) administration on progesterone
      and cortisol concentrations was determined in lactating primiparous sows.
      Physiological saline and 50 IU ACTH were administered on days 20 and 21 of
      lactation at 0900 hours via an indwelling jugular catheter. Blood samples for
      hormone analysis were collected via indwelling jugular catheters every 15 min
      (0800 to 1200 hours) and every 60 min (1300 to 1500 hours). Saline administration
      had no effect on progesterone nor cortisol concentrations in the lactating sows.
      Progesterone and cortisol concentrations increased (p < 0.001) within 15 min
      after ACTH administration. Progesterone and cortisol concentrations peaked (p <
      0.01) within 45 min and had returned to pretreatment values within 120 min after
      ACTH treatment.

PMID- 9592946
TI  - Urinary excretion of oestrone sulphate and cortisol in early pregnant gilts
      treated with glucocorticoids.
AB  - The aim of this study was to determine rates of urinary excretion of oestrone
      sulphate and cortisol in early pregnant gilts that were untreated or treated with
      either dexamethasone, corn oil or hydrocortisone. Twenty Polish Landrace gilts
      were used. They were grouped immediately after mating as follows: Experiment I-
      Group 1 (5 gilts), control animals and Group 2 (5 gilts), injected i.m. with
      dexamethasone (30 micrograms/kg) at 12-h intervals from day 13 to day 22 of
      pregnancy; Experiment II--Group 3 (5 gilts), injected i.m. with corn oil at 12-h
      intervals from day 13 to day 22 of pregnancy and Group 4 (5 gilts), injected i.m.
      with hydrocortisone acetate (250 mg) at 12-h intervals from day 11 to day 20 of
      pregnancy. Gilts were placed in metabolic cages, and 24-h urine aliquots were
      collected from day 6 to day 32 of pregnancy. On days 34-36 of pregnancy gilts
      were slaughtered and clinical data were collected. Rates of urinary excretion of
      oestrone sulphate and cortisol were determined by enhanced chemiluminescence
      immunoassays. The urinary excretion of oestrone sulphate expressed in nmol/24 h
      and mumol/mol creatinine were significantly correlated. There was no correlation
      between cortisol expressed in nmol/24 h and mumol/mol creatinine (p > 0.5). A
      first significant increase of urinary oestrone sulphate excretion, expressed in
      nmol/24 h, on days 13-14 and a second one on days 19-20 of gestation occurred in
      control untreated and oil-treated gilts. The urinary excretion of oestrone
      sulphate reached maximum values between days 25 and 32 of gestation. In
      dexamethasone-treated gilts cortisol excretion significantly decreased on day 16,
      i.e. 3 days after injections of dexamethasone had commenced. The treatment with
      hydrocortisone resulted in a significantly increased cortisol excretion after the
      last injection of hydrocortisone. There were no relations between levels of
      urinary oestrone sulphate excretion expressed in nmol/24 h and the number of
      foetuses. When the urinary excretion of oestrone sulphate was expressed in
      mol/mol creatinine we found a positive relation between concentrations on day 20
      of pregnancy and the number of foetuses. In one untreated gilt with a relatively
      high urinary excretion of cortisol (more than 200 nmol/24 h) a lower number of
      foetuses was found at autopsy. In conclusion, both dexamethasone and
      hydrocortisone treatment seemed to delay the first observed peak in oestrone
      sulphate in gilts without affecting the embryonic survival and the number of
      viable foetuses.

PMID- 9592948
TI  - The effect of peroral administration of amino acid-chelated iron to pregnant sows
      in preventing sow and piglet anaemia.
AB  - Two trials were performed in 2 different pig herds. In Trial 1, 9 pregnant
      Norwegian landrace sows were given a supplement in the feed of about 300 mg iron
      daily as amino acid-chelated iron (Bio-plex) during the last 3 weeks of
      gestation. Ten sows were included as controls. In Trial 2, 10 sows were fed a
      supplement of about 650 mg iron daily as glutamic acid-chelated iron (Super Fe
      MAX) during the same period of pregnancy as in Trial 1. Twenty-two sows were
      included as controls. Blood samples were taken from the sows at the start of the
      experiment and on the day after parturition. The sows in Trial 1 were also bled
      at weaning 5 weeks after parturition. The piglets were weighted and blood samples
      collected 24 +/- 12 h after birth. Livers were taken from 65 piglets, which were
      either still-born or which died or were euthanised as one-day olds, and examined
      for iron content. The erythrocyte count (RBC), haemoglobin concentration (HGB),
      mean cell volume (MCV), erythrocyte distribution width (RDW), and haemoglobin
      distribution width (HDW) in blood were measured. Haematocrit (HCT), mean cell
      haemoglobin (MCH), and mean cell haemoglobin concentration (MCHC) were also
      estimated. Blood serum was analysed for total proteins, albumin, serum Fe, and
      total iron-binding capacity (TIBC). A slight increase in HGB and RBC in the
      piglets from the iron-treated sows compared with the controls was found in Trial
      1, but this was considered to be of no practical importance. None of the other
      measured parameters were influenced by treating the pregnant sows with amino acid
      chelated iron.

PMID- 9592949
TI  - The duration of antibodies against bovine virus diarrhoea virus in bulk milk.
AB  - Fifty-eight dairy herds, suspected to be recently infected with bovine virus
      diarrhoea virus (BVDV) due to a rise in BVDV antibodies in bulk milk, were
      followed over a two-year period. In 34 (59%) of these 58 herds (Group 1), pooled
      milk samples from heifers or pooled blood samples from calves were negative for
      BVDV antibodies. In this group as many as 53 and 76% of the herds again had
      antibody-negative bulk milk one and two years after the positive sample,
      respectively. Of the remaining herds, 5 and 17% had negative samples after one
      and 2 years respectively. Possible explanations for the limited duration of
      antibodies against BVDV in bulk milk are discussed. In 65% of the herds in Group
      1, animals had been purchased and introduced into the herd, or the herds had been
      exposed to other forms of contact representing a risk of infection with BVDV. In
      the remaining 35% of the herds in this group, no explanation for the rise in BVDV
      antibodies in the bulk milk could be found. In this study the introduction of
      seropositive animals into the herd, and infection inducing seroconversion in one
      or more animals as the only result, seem to be the most probable explanations for
      the rise in antibody levels observed in Group 1.

PMID- 9592950
TI  - The effect of bovine virus diarrhoea virus on reproduction in recently infected
      Norwegian dairy herds.
AB  - A group of 32 dairy herds, recently infected with bovine virus diarrhoea virus
      (BVDV), was compared with a control group consisting of 75 BVDV free herds during
      a 3-year-period. Variables related to reproduction were registered. Results of
      multiple antibody examinations in bulk milk as well as samples of milk and blood
      from younger animals were used to select the herds. The incidence of abortions
      was statistically significantly different in the 2 groups, while the number of
      stillbirths, weak born calves, and congenital anomalies was not. Other variables
      such as percentage of non return, average number of inseminations per cow and
      calving interval showed during the study a trend to improve in the BVDV group,
      while they remained stable in the control group.

PMID- 9592951
TI  - Control of caprine arthritis-encephalitis virus and Corynebacterium
      pseudotuberculosis infection in a Norwegian goat herd.
AB  - A control programme for caprine arthritis-encephalitis virus (CAEV) and
      Corynebacterium pseudotuberculosis (C. pseudotuberculosis) infection was
      established in a Norwegian goat herd comprising approximately 100 milking goats.
      The herd seroprevalences of antibodies against CAEV and C. pseudotuberculosis
      were 97% and 94%, respectively. Kids were removed from the infected flock at
      birth, avoiding any contact between dam and kid. The kids were kept completely
      segregated from the seropositive flock and fed cow's colostrum and milk. A
      seronegative flock was established, based on the removed kids and their
      offspring. Goasts belonging to the seronegative flock were allowed to kid
      naturally and to mother their kids. The seropositive flock was slaughtered during
      the second year of the control programme. After washing and disinfection, housing
      systems and nearby outdoor premises were left empty for 3 months. Of 230 goats
      examined for antibodies against CAEV with ELISA regularly during 3 years of the
      control program, altogether 6 were found to be seropositive, while for 10 the
      result was indeterminate. All 16 animals were immediately culled. During the
      third year of the control programme, all goats were examined and proved negative
      for antibodies against C. pseudotuberculosis by a haemolysis inhibition test.
      Clinical examination revealed no signs of CAE or caseous lymphadenitis.

PMID- 9592952
TI  - Bovine mastitis in Finland in 1988 and 1995--changes in prevalence and
      antimicrobial resistance.
AB  - Two surveys were carried out (during 1988 and 1995) to estimate the prevalence of
      bovine mastitis in Finland. In 1988, 17,111 quarter milk samples were obtained
      from 4495 cows, and in 1995 the corresponding figures were 10,410 and 2648.
      Antimicrobial susceptibility of mastitis pathogens was studied. Prevalence of
      mastitis on cow basis decreased from 47.8% in 1988 to 37.8% in 1995.
      Staphylococci was the largest group of pathogens isolated. The proportion of
      Staphylococcus aureus decreased and that of coagulase-negative staphylococci
      (CNS) increased. The proportion of strains resistant to at least one
      antibacterial drug increased with regard to S. aureus from 36.9% in 1988, to
      63.6% in 1995 and with CNS from 26.6% to 49.7%. Most of the increase in
      antibacterial resistance was due to a higher number of beta-lactamase producing
      strains. Multiresistance also increased, but it was proportional to the overall
      increase in resistance. All the predominant mastitis streptococci were
      susceptible to beta-lactams tested.

PMID- 9592953
TI  - Medetomidine-midazolam sedation in sheep.
AB  - Seven sheep were sedated 3 times: with medetomidine (15 micrograms kg-1), with
      midazolam (0.1 mg kg-1) and with a combination of the drugs. All drugs were
      administered intravenously. Heart and respiratory rates were measured. Arterial
      blood samples were collected, and PaO2, PaCO2, pH, haemoglobin concentration and
      saturation, and base excess were determined. Systolic and mean arterial pressures
      were recorded before and after the treatment with medetomidine-midazolam.
      Midazolam increased the time of recumbency induced by medetomidine. After
      administration of midazolam alone, 4 of the 7 sheep were sedated and the other 3
      were excited. Heart rate decreased after both medetomidine and medetomidine
      midazolam. One sheep suffered a cardiac arrest after medetomidine-midazolam
      injection, and it required resuscitation. PaO2 and haemoglobin oxygen saturation
      decreased after medetomidine, and medetomidine-midazolam caused a marked
      hypoxaemia. PaCO2 increased after medetomidine, both alone and combined with
      midazolam, but arterial pH was within the reference values after all drug
      administrations. Systolic and mean arterial pressures decreased after
      medetomidine-midazolam. This study indicates that though in sheep midazolam
      potentiates the sedative effect of medetomidine, the combination of medetomidine
      and midazolam also reduces the in PaO2 and haemoglobin oxygen saturation more
      than medetomidine alone. The results indicate that a medetomidine-midazolam
      combination is unsafe for sheep at the doses studied.

PMID- 9592954
TI  - Endotoxin-effects of vaccination with Escherichia coli vaccines in the pig.

PMID- 9592956
TI  - Antimicrobial susceptibility of Mycoplasma hyorhinis in a liquid medium compared
      to a disc assay.

PMID- 9592955
TI  - Comparison of two techniques used for quantification of ovine gastrointestinal
      nematode larvae in herbage.

PMID- 9592957
TI  - The Tomera technique: high energy transurethral thermotherapy with low energy
      morbidity.
AB  - Transurethral Microwave Thermotherapy (TUMT) is a unique and promising method of
      treating benign prostatic hyperplasia. Clinical outcomes after high energy
      protocol TUMT 2.5 are comparable to transurethral resection of the prostate.
      Previously this increased efficacy has had greater morbidity than lower energy
      protocol TUMT 2.0 with catheterization required in all patients. A technique of
      careful preoperative patient teaching, intravenous ketorolac and remifentanyl;
      patient discomfort is minimized, bladder spasms avoided, and requirement for
      catheterization infrequent. In 16 consecutive patients, only four required
      catheters despite an average energy of 155 KJ and a maximum energy of 208 KJ.

PMID- 9592958
TI  - The financial impact of alcohol-related emergencies on a rural EMS system.
AB  - HYPOTHESIS: Alcohol is a major factor in ambulance responses in rural Alaska;
      alcohol-related emergencies significantly increase the expense of operating an
      advanced life support ambulance service. METHODS: A prospective analysis was
      performed on emergency medical responses one year, ending September 30, 1997.
      Data were collected from medical records, police documents, and court records.
      ANALYSIS: Each ambulance response was analyzed for the presence of alcohol. The
      departmental budget was reviewed to separate out fixed and variable costs.
      Between these analyses, a determination was made regarding the actual cost of all
      alcohol-related ambulance responses. RESULTS: Six hundred eighty-one patients
      were included for study. Alcohol was a factor in one hundred ninety-one (28.0%)
      of these patients. The cost to the community for alcohol-related responses
      amounted to $81,503, representing 19.2% of the budget. CONCLUSION: The cost to
      respond to alcohol-related emergencies represents a significant fraction of
      Ketchikan's total emergency medical budget.

PMID- 9592959
TI  - National Health Service Corps celebrates 25 years of delivering health care in
      underserved areas.

PMID- 9592960
TI  - MMR vaccine is not linked to Crohn's disease or autism.

PMID- 9592961
TI  - Outbreak of hepatitis B associated with autohaemotherapy: update.

PMID- 9592962
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9592963
TI  - PHLS study of infections with multidrug resistant Salmonella typhimurium DT104
      has recruited enough cases.

PMID- 9592964
TI  - Evidence to support current policy on MMR vaccination sent to doctors in the
      United Kingdom.

PMID- 9592965
TI  - [Perspectives in the use of GnRh antagonists].

PMID- 9592966
TI  - [Oxytocic drugs].

PMID- 9592967
TI  - [The urban gynecologist and the management of menometrorrhagia: role of
      ultrasonography].

PMID- 9592969
TI  - [Certainty and anxiety about intracytoplasmic sperm insemination].

PMID- 9592968
TI  - [Risks of human embryo cryopreservation].

PMID- 9592970
TI  - [Propositions for a better practice. Point of view of a specialist].
AB  - Pregnancy management is a typical medical shared follow up, between general
      practicioner and the specialist, in charge of birth process, in the Obstetrical
      Center. To improve this health care net coordination, propositions are made based
      upon most frequently done errors analysis, practicioner and specialist errors
      too.

PMID- 9592972
TI  - [Therapeutic abortion. Critical study of 22 cases].
AB  - The abortion for medical reasons is the only abortion allowed in Morocco and it
      aims to preserve maternal health or to forewarn the birth of handicaped children.
      The author has ascribed 22 cases of medical abortion, their indications have
      maternal origin in 91% cases. In europeans series the indication have 80% of
      foetal origin. In order to change the profil of our indications, the author
      insists on the necessity to program the pregnancy in maternal pathology, to
      eliminate an early, pregnancy before any therapeutical act and to encourage
      antenatal diagnosis according to legal dispositions.

PMID- 9592971
TI  - [What does the general practitioner expect from his colleague the gynecologist
      obstetrician?].
AB  - The upgrading of pregnant women care, requires a change of mind. The question is
      to centre the pregnant woman in a complicated care system. The different
      intervening practicioners must learn how to work together, in the way of a
      coordonition care; each one knowing his own limits and acting as well as he
      could. 60% of pregnant women with a normal pregnancy could be ambulatory managed
      by their general practitioner, in a conjoined follow with the obstetrician. High
      risk and pathologic pregnancies would be priority followed into obstetrical
      hospital department, according to each woman requirement, in collaboration with
      her general practitioner. The conjoined follow experimentations show that they
      are successful on perinatal deathrate and morbidity decriment. It's time to take
      up this challenge.

PMID- 9592974
TI  - [Contraceptive behavior of young Latin-American adults living in Montreal].
AB  - Recent research on the contraceptive practices of Hispanics adolescents living in
      Latin America and the United-States indicates that their practices are
      inadequate. However, contraceptive practices can vary according to levels of
      traditionalism and acculturation. In order to verify these hypotheses, the
      contraceptive behaviors of a group of 114 young adults from both genders of
      Hispanic origin were evaluated. Results indicate that half of the participants
      did not use any contraceptive method during the first intercourse and that
      condoms were the most common method. Contrary to American results, acculturation
      levels were not significant in contraceptive use. Degree of traditionalism in
      sexual roles was more significant.

PMID- 9592973
TI  - [Pregnancy after tubal sterilization. Experience at the University Hospital
      Center of Dakar].
AB  - Between January 1991 and December 1996, 856 women had a tubal sterilization by
      minilaparotomy under local anesthesia in obstetric and gynaecologic clinic of
      University Teaching Hospital of Dakar. Among her 5 became pregnant after 7 to 54
      months (mean 19 months). The failure rate is 5.84 per 1,000; all 5 women had
      intra-uterine pregnancy. The women were age 35-43 years (mean 38 years) and
      multiparity with 8 children. The main causes of failure was technical error and
      tubal peritoneal fistula. Favorables factors has been represented by inexperience
      of surgeons and also per-operations difficulties particularly dues to strucked
      fallopian tubes. 4 has delivered a healthy child with one by cesarean section, in
      3 cases she decided to be sterilized again after delivery.

PMID- 9592975
TI  - [Onset of labor in human parturition].

PMID- 9592976
TI  - Medical editors trial amnesty.

PMID- 9592977
TI  - P-glycoprotein (PGP), and not lung resistance-related protein (LRP), is a
      negative prognostic factor in secondary leukemias.
AB  - BACKGROUND AND OBJECTIVE: In cell lines, there is an ongoing debate about the
      role of the lung resistance-related protein (LRP) whereas the role played by P
      glycoprotein (PGP) in determining a multidrug resistance is well known. The aim
      of this study was to evaluate the frequency and the role of a PGP and an LRP
      overexpression in affecting the intracellular daunorubicin accumulation (IDA) and
      in predicting the therapy outcome on a subset of overt secondary acute non
      lymphocytic leukemias (ANLL). An adjunctive point was to evaluate the efficacy of
      the reversal agent SDZ PSC 833 (PSC) in counteracting impaired IDA. DESIGN AND
      METHODS: By flow cytometry, PGP and LRP expression and the IDA were evaluated on
      54 overt secondary ANLL PGP and LRP overexpressions were respectively defined by
      an MRK-16 mean fluorescence index (MFI) > or = 6 (PGP+) and by an LRP-56 MFI > or
      = 5 i.e. by MRK-16 and LRP-56 MFIs higher than the one observed in normal
      leukocytes. The blasts' IDA was studied after a two-hour incubation in 1000 ng/mL
      daunorubicin in the presence or in the absence of the MDR reversal agent SDZ PSC
      833 (PSC) 1.6 mumol. RESULTS: A PGP overexpression was detected in 40/54 (74%)
      cases while an LRP overexpression was observed on 33/54 (61%) cases. No
      differences were found in terms of PGP and LRP expressions between ANLL
      developing after chemo/radiotherapy (therapy-related ANLL) or evolving from a
      myelodysplastic syndrome (MDS-related ANLL). Compared to the PGP-, the PGP+ cases
      showed a significantly lower mean IDA (DNR NMFI 196 +/- 46 vs. 267 +/- 53, p <
      0.001). The co-incubation of DNR with the PSC significantly increased only the
      mean IDA of the PGP+ cases, that grew from a DNR NMFI of 196 +/- 46 to a DNR NMFI
      of 284 +/- 67 (p < 0.0001). With respect to normal leukocytes, even the PGP-
      cases had an impaired IDA suggesting that other mechanisms, including an LRP
      overexpression, could affect the IDA. A strongly negative correlation was
      observed between PGP overexpression and therapy outcome, in fact, 8/10 (80%) PGP-
      but only 2/27 (7%) PGP+ patients obtained complete remission (p = 0.0002).
      Moreover, 7/33 (21%) cases showing an impaired IDA (NMFI < 280) but 4/4 (100%)
      with NMFI > 280 had complete remission (p = 0.006). No correlation was found
      between therapy response and LRP or CD34 expression. INTERPRETATION AND
      CONCLUSIONS: This data suggests that an important role in determining therapy
      outcome is played by PGP in secondary leukemias. Even if the LRP is frequently
      overexpressed in secondary leukemias and is likely to contribute to the reduction
      of the intracellular drug accumulation, the role played by LRP in determining the
      therapy-outcome has still to be cleared.

PMID- 9592978
TI  - bcl-2 expression in plasma cells from neoplastic gammopathies and reactive
      plasmacytosis: a comparative study.
AB  - BACKGROUND AND OBJECTIVE: bcl-2 oncoprotein plays a major physiological role in
      hemopoietic and non-hemopoietic cells by preventing apoptosis (programmed cell
      death). Disregulation of this process may be important in oncogenesis and the
      response to treatment of patients with different hematological malignancies. We
      have investigated the levels of bcl-2 expression in plasma cells from patients
      with reactive plasmacytosis (RP), monoclonal gammopathy of unknown significance
      (MGUS) and multiple myeloma (MM), correlating the bcl-2 expression and clinico
      biological features in MM patients. DESIGN AND METHODS: The percentage of bcl-2
      (+) plasma cells and levels of bcl-2 protein expression were investigated in 73
      patients at diagnosis. Immunofluorescence and immunoenzymatic methods were
      applied using McAb against bcl-2 protein, and the intensity of protein expression
      was assessed by both the mean channel fluorescence intensity (MFI) and
      semiquantitative methods. To evaluate the intensity of bcl-2 expression in
      proliferating plasma cells, sequential double immunoenzymatic staining with McAb
      Ki-67 and bcl-2 was applied in 10 patients with MM. Correlations between bcl-2
      expression and the clinico-biological features in MM patients were also studied.
      RESULTS: The proportion of bcl-2 (+) plasma cells was significantly higher in
      MGUS and MM than in RP (p < 0.001). The intensity of bcl-2 expression in plasma
      cells (assessed by MFI) was significantly different between all groups studied (p
      < 0.0001). RP showed lower expression than MGUS and MM patients. MM stage III
      patients demonstrated higher bcl-2 expression values than MGUS (p < 0.01).
      According to the proportion of plasma cells expressing Ki-67, patients with a
      proliferative index (Ki-67+) > 4% showed lower bcl-2 expression than patients
      with proliferative index < 4% (p < 0.05). Immunocytochemistry showed that plasma
      cells from RP had a lower intensity of bcl-2 expression than MM (p < 0.001), and
      double immunostaining Ki-67/bcl-2 demonstrated that the majority of proliferating
      plasma cells had weak bcl-2 expression. There was no correlation between bcl-2
      expression and clinico-biological parameters, response to therapy or overall
      survival in MM patients. INTERPRETATION AND CONCLUSIONS: Globally, the number of
      bcl-2 (+) plasma cells and the intensity of protein expression in neoplastic
      gammopathies are significantly higher than in reactive plasmacytosis and bcl-2
      levels tend to increase with disease stage. bcl-2 may be relevant to the
      pathogenesis of malignant gammopathies, prolonging the survival of plasma cells
      by preventing apoptosis and increasing the chance of acquiring additional gene
      defects. bcl-2 expression could also contribute to the resistance to chemotherapy
      observed in MM disease.

PMID- 9592979
TI  - Characterization and viral safety validation study of a pasteurized therapeutic
      concentrate of antithrombin III obtained through affinity chromatography.
AB  - BACKGROUND AND OBJECTIVE: Antithrombin III (ATIII) concentrates are employed as
      therapy for congenital or acquired deficiencies. These concentrates are obtained
      from Cohn's fraction IV1. To improve yields, purity and safety, our group
      developed a procedure to obtain a pasteurized ATIII concentrate from the
      supernatant of Cohn's fraction II + III including a highly efficient heparin
      affinity chromatography purification and pasteurization as a viral inactivation
      step. DESIGN AND METHODS: Three steps of the manufacturing procedure (Cohn's
      fraction II + III precipitation, affinity chromatography and pasteurization) were
      selected to examine their efficacy in inactivating and/or removing the selected
      viruses. RESULTS: The industrial batches show a purity higher than 99% with
      approximately 95% native heparin binding ATIII. Only albumin and IgG could be
      detected at trace levels (0.07% and 0.16% of the total protein present,
      respectively). The specific activity of the product was approximately 6.65 IU/mg
      protein. Five viruses were spiked into the manufacturing starting materials and
      samples were collected at various points to determine the infection level of
      virus. The study showed a reduction factor (log 10) > or = 11.7 for HIV-1; > or =
      8.1 for bovine herpes virus (analyzed as a model for herpes and hepatitis B
      viruses); > or = 8.1 for bovine diarrhea virus (model for hepatitis C and G) and
      > or = 6.0 for encephalomyocarditis virus (model for hepatitis A and other non
      enveloped viruses). INTERPRETATION AND CONCLUSIONS: No biochemical alterations of
      the ATIII were detected in the final product. A high viral elimination capacity
      of the production process was demonstrated. So far, more than 32 million units of
      ATIII have been transfused in the form of this therapeutic concentrate without
      any detected seroconversion.

PMID- 9592980
TI  - Mantle cell lymphoma: a retrospective study on 27 patients. Clinical features and
      natural history.
AB  - BACKGROUND AND OBJECTIVE: Mantle cell lymphoma (MCL) is a separate histological
      and clinical entity recently recognized in the new revised European-American
      Lymphoma Classification. Little information exists regarding its therapy. We
      report the results of a retrospective study of 27 patients affected by MCL
      evaluating the clinical characteristics and the results of different
      therapeutical options used during the period of observation. DESIGN AND METHODS:
      From 1983 to 1993, we observed 27 patients affected by MCL according to the
      criteria proposed by European Lymphoma Task Force in a revision of 55 cases
      classified as NHL E according to Working Formulation (WF) criteria. We analyzed
      the clinical characteristics, the prognostic factors and the O.S. of these
      patients. RESULTS: The clinical characteristics of our patients (pts) are similar
      to those observed in other series: male prevalence, median age 62 years, B
      symptoms in 9 cases, P.S. > 2 in 11 cases, 3 pts were in stage I and II, 4 in
      stage III, 20 in stage IV; 18 pts had a bone marrow involvement, 13 pts had
      spleen enlargement and 14 had extranodal localization; 8 pts had bulky tumor and
      5 had LDH above normal. The CR rate was 51.8%, the median O.S. was 43 months, and
      DFS was 18 months; the pts without bulky disease and with localized disease had a
      better CR rate. The inclusion of an anthracycline in the regimen did not affect
      the results. INTERPRETATION AND CONCLUSIONS: Our results were not divergent from
      those present in literature. The mantle cell lymphoma is an incurable and highly
      aggressive disease. Autologous bone marrow transplantation as support of high
      dose chemotherapy or allogenic bone marrow transplantation may be a chance for
      some patients, but not for the majority of patients, which are older than 65
      years. Studies of a larger series and different therapeutical approaches, i.e.
      using biological modifiers in association or as maintenance after chemotherapy
      are essential.

PMID- 9592981
TI  - Effects of recombinant granulocyte colony-stimulating factor (G-CSF) in patients
      treated with ProMACE-CytaBOM for HIV-related non-Hodgkin's lymphoma (NHL).
AB  - BACKGROUND AND OBJECTIVE: The use of hematopoietic growth factors in association
      with chemotherapy in human immunodeficiency virus (HIV)-related non-Hodgkin's
      lymphoma (NHL) has been recommended, but few studies have evaluated its cost
      effectiveness. DESIGN AND METHODS: The effects of recombinant granulocyte colony
      stimulating factor (G-CSF) were analyzed in 33 consecutive patients with HIV
      related NHL treated at a single institution with the same chemotherapy program,
      ProMACE-CytaBOM, with G-CSF, in 21 cases diagnosed after December 31, 1991, or
      without G-CSF, in 12 cases diagnosed earlier. Pearson's chi-square analysis and
      the two-sided Student's t-test were used for statistical comparisons. The method
      of Kaplan-Meyer and the log-rank-test were used for survival analyses. RESULTS: G
      CSF support significantly reduced the frequency of day-1 drug dose reductions (p
      < 0.001) and of chemotherapy delays (p < 0.001), and improved the actual
      delivered doses of adriamycin, cyclophosphamide and etoposide (p < 0.02). In
      patients with a CD4+ count < 0.01 x 10(9)/L, chemotherapy could be given at full
      doses in 90% of cycles with G-CSF compared to only 20% without it. G-CSF affected
      neither the frequency and duration of fever and hospitalization nor the complete
      remission and survival rates after stratification according to the CD4+ count.
      INTERPRETATION AND CONCLUSIONS: G-CSF support significantly improved dose
      intensity in patients with HIV-related NHL treated with aggressive chemotherapy,
      particularly in the subgroup with a CD4+ count < 0.1 x 10(9)/L, but it did not
      improve their clinical outcome.

PMID- 9592982
TI  - Efficacy of a combination of idarubicin, etoposide and intermediate-dose cytosine
      arabinoside as salvage therapy in relapsing or resistant unfavorable lymphoma.
AB  - BACKGROUND AND OBJECTIVE: Idarubicin, an anthracycline analogue, is active in non
      Hodgkin's lymphoma. This study evaluates the efficacy and toxicity of a
      combination of idarubicin, etoposide and intermediate-dose cytarabine (IVA) in
      unfavorable lymphoma in relapse or resistant to prior doxorubicin- or novantrone
      based regimens. DESIGN AND METHODS: Thirty patients with relapsing or resistant
      unfavorable lymphoma received a combination of idarubicin 12 mg/m2 i.v. on day 1,
      etoposide 60 mg/m2 i.v. every 12 hours for 3 days, and Ara-C 1 g/m2 i.v. every 12
      hours for 3 days (3-hour infusion). Median age was 39 years (range: 22-60). All
      patients had been given prior doxorubicin or novantrone; 54% of them had received
      2 or more chemotherapy regimens; 67% of total were in clinical relapse (30% in
      their second relapse), and 23% had resistant disease. RESULTS: The overall
      response rate to IVA was 60% (18 of 30 patients). Complete remission rate was 20%
      (6 of 30) in the whole group, 45% (5 of 11) among patients in their first
      relapse. Remission median duration was 9 months (range: 1-18), with a 3-year
      relapse-free and overall survival of 20% and 15%, respectively. Severe
      neutropenia occurred in 13 patients (43%) and severe thrombocytopenia in 11
      patients (37%), with a median duration of 9 and 13 days, respectively. No cardiac
      toxicity developed; sepsis during neutropenia was documented in four instances
      and two patients (7%) died of therapy-related events (septic shock).
      INTERPRETATION AND CONCLUSIONS: Idarubicin combined with etoposide and
      intermediate-dose cytarabine proved to be an active salvage therapy in
      unfavorable lymphoma given prior doxorubicin or novantrone; the best results were
      obtained among patients in their first relapse, with low tumor burden.

PMID- 9592983
TI  - Factors affecting hemopoietic recovery after high-dose therapy and autologous
      peripheral blood progenitor cell transplantation: a single center experience.
AB  - BACKGROUND AND OBJECTIVE: While the minimum number of CD34+ cells required for
      complete and long-lasting engraftment is quite well established, there is not
      general agreement about the optimal number of CD34+ per kg needed in order to
      obtain engraftment as rapidly as possible. In the present study we assess factors
      affecting hemopoietic recovery and the optimal peripheral blood progenitor cell
      (PBPC) number for rapid engraftment in patients treated with high-dose therapy.
      DESIGN AND METHODS: We enrolled 80 consecutive patients affected by hematologic
      and non-hematologic malignancies treated with a median of 10 chemotherapy courses
      (range 3-38). PBPC collection was performed after mobilization with high-dose
      chemotherapy and G-CSF 5 micrograms/kg/day. The circulating and harvested CD34+
      cells were recognized in the cytofluorimetric CD45+/CD14- lymphocyte gate. After
      myeloablative therapy, PBPC infusion was followed by G-CSF 5 micrograms/kg/day
      from day +5 until WBC > or = 5.0 x 10(9)/L. Univariate and multivariate Cox
      analyses were performed to investigate factors affecting hemopoietic recovery.
      The Kaplan-Meier probabilities of hemopoietic reconstitution were compared by log
      rank test to assess the optimal CD34+ cell number for rapid engraftment. RESULTS:
      We performed a median of two apheresis (range 1-4) per patient and we infused a
      median of 6.1 x 10(6) CD34+ cells/kg (range 0.5-30.5). Absolute neutrophil count
      (ANC) > 0.5 x 10(9)/L was reached after 11 days (range 8-15). The only factor
      affecting granulocyte recovery proved to be the CD34+ cell number; 5.0 to 7.8 x
      10(6) CD34+ cells/kg allowed a significantly faster granulocyte recovery than <
      2.5 x 10(6) CD34+ cells/kg (p = 0.0312). Platelet transfusion independence (> 20
      x 10(9)/L) and 50 x 10(9)/L platelets were reached after 12 (range 8-24) and 15
      days (range 9-40), respectively. The CD34+ cell number was also the only factor
      affecting platelet recovery; the number of 5.0 to 7.8 CD34+ cells/kg allowed a
      significantly faster platelet recovery than the lower dose, whereas a higher
      number did not. No late graft failures were observed. Patients receiving 5.0 to
      7.8 x 10(9) CD34+ cells/kg had a significantly shorter duration of neutropenia,
      fewer platelet transfusions and less time spent in hospital than those receiving
      lower number did, whereas patients transplanted with a higher number had no
      advantage. INTERPRETATION AND CONCLUSIONS: When G-CSF is employed both for PBPC
      mobilization and after PBPC transplantation, the CD34+ cell number is the only
      factor that affects hemopoietic recovery. Moreover, > 5.0 x 10(6) CD34+ cells/kg
      is the optimal number for obtaining rapid platelet recovery and reducing the
      costs of HDT but there is no advantage exceeding the threshold of 7.8 x 10(6)
      CD34+ cells/kg.

PMID- 9592984
TI  - Hemostasis and blood requirements in orthotopic liver transplantation with and
      without high-dose aprotinin.
AB  - BACKGROUND AND OBJECTIVE: Several factors seem to lead to considerable bleeding
      and transfusion requirements during orthotopic liver transplantation (OLT) and
      postoperatively, but hyperfibrinolysis appears to be the most important factor.
      Aprotinin, a broad-spectrum serine protease inhibitor, has been shown to inhibit
      hyperfibrinolytic states. DESIGN AND METHODS: A non-randomized, controlled
      clinical trial was performed to assess the efficacy of aprotinin in 20
      consecutive OLT procedures (group A). The results obtained were compared with the
      findings in two groups of patients who did not receive aprotinin: one control
      group (C1) consisting of the 20 consecutive recipients who underwent OLT
      immediately prior to group A, and a second control group (C2) consisting of the
      30 consecutive recipients undergoing OLT immediately after group A. Twenty-three
      hemostatic parameters were studied in group A and C1 and the blood product
      requirements were compared in all three group. RESULTS: We observed a markedly
      reduced fibrinolysis in group A during the non-hepatic and reperfusion phases
      demonstrated by reduced tissue-type plasminogen activator (t-PA), alpha 2
      antiplasmin-plasmin complex (APP) and D dimer levels and an increase in
      antiplasmin activity compared to C1 group (p < 0.05). In vitro experiments showed
      aprotinin to have an antiplasmin effect. The intraoperative transfusion of units
      of RBC and fresh frozen plasma (FFP) was significantly diminished in group A (8.1
      and 16.7 U, respectively) when compared with groups C1 (20.4 and 36.0 U) and C2
      (13.0 and 28.0 U) (p < 0.05); there was also a significantly greater number of
      patients not requiring intraoperative platelet transfusion in group A (p < 0.05).
      During the first 5 postoperative days, the number of patients in group A who did
      not require RBC transfusion was significantly larger than in groups C1 and C2 (p
      = 0.04). INTERPRETATION AND CONCLUSIONS: In this study, the inhibition of
      fibrinolysis associated with the prophylaxis with aprotinin, administered in high
      doses by continuous intravenous infusion, appears to reduce the need for blood
      product transfusion during the OLT procedure.

PMID- 9592985
TI  - Decision making at the bedside: diagnosis of hereditary spherocytosis in a
      transfused infant.
AB  - A large group of hereditary spherocytosis (HS) patients manifest the clinical
      signs of this condition during the neonatal period and most of them require
      transfusions. The authors describe a clinical case of a neonate that was
      transfused. They demonstrated that the splenectomized mother had an HS due to a
      de novo mutation of one ankyrin allele. By means of this molecular approach, they
      were able to perform a diagnosis of HS in the newborn. The administration of
      rhEpo during the first months of life created a condition of transfusion
      independence and, after six months, they were able to demonstrate the biochemical
      defect on the red cell membrane.

PMID- 9592986
TI  - ALL1 gene alterations in acute leukemia: biological and clinical aspects.
AB  - BACKGROUND AND OBJECTIVE: The ALL1 gene, also referred to as MLL, HRX or Htrx1,
      is interrupted in the vast majority of translocations involving the chromosome
      band 11q23. Alterations in this gene are reported in approximately 5-10% of acute
      leukemias (AL) and characterize different leukemic subtypes such as infant (< 12
      months of age) AL, topoisomerase II inhibitors-related (TR) AL and a small subset
      of de novo AML and ALL. Distinguishing features of ALL1 alterations include the
      striking heterogeneity of its recombinations, i.e., more than 30 chromosome
      partners have been described in ALL1 rearrangements, and the lack of association
      with a definite lineage. The objective of this article is to review the
      biological and structural properties of ALL1 gene and its various fusion
      proteins, and to discuss the clinical relevance of these lesions with special
      emphasis on their role in molecular diagnosis and monitoring of minimal residual
      disease. EVIDENCE AND INFORMATION SOURCES: The material examined in the present
      review includes data published by the authors in this field, articles and
      abstracts published in journals covered by the Science Citation Index and
      Medline, as well as some more recent personal unpublished observations. STATE OF
      THE ART: The ALL1 gene spans approximately 90 kb of DNA in length, and consists
      of 36 exons, ranging in size from 65 bp to 4249 bp. ALL1 codifies for a major
      transcript of approximately or equal to 15 kb. It encodes a protein of more than
      3910 amino acids, containing three regions sharing sequence homology with the
      Drosophila trithorax gene. These homologies suggest that ALL1 is a transcription
      factor controlling development and/or differentiation of human cells. To date,
      twelve ALL1 partner genes have been characterized which are involved in the
      following translocations: t(4;11), t(9;11), t(6;11), t(11;19), t(1;11) t(10;11),
      t(11;16), t(11;17) and t(X;11). Since all these genes do not share relevant
      homologies among each other, their putative role in ALL1 activation still remains
      to be clarified. The analysis of ALL1 breakpoint cluster region (bcr) shows that
      several DNA motifs implicated in illegitimate recombination events are located
      within the bcr. Thus, mapping of breakpoints in the different subtypes of ALL1
      +ve leukemia may help in understanding the events leading to translocations in
      human ALs. In this respect, data on ALL1 breakpoint localization suggest that
      similar pathogenetic mechanisms may underlie infant and TR AL and that these
      events might differ from those occurring in de novo AL. The availability of this
      molecular marker provides a new tool for diagnostic purposes and characterization
      of ALs and for monitoring of minimal residual disease. To date, the prognostic
      value of ALL1 rearrangements has been clearly demonstrated for infant ALs only,
      whereas the clinical relevance of ALL1 rearrangements in the other leukemic
      subtypes needs further evaluation by future prospective studies on a larger
      number of patients homogeneously treated. As concerning studies on minimal
      residual disease, data on PCR monitoring of the ALL1/AF4 fusion transcript,
      resulting from the t(4;11) translocation, show the clinical relevance of this
      molecular test in predicting outcome and, as a consequence, in designing
      individual post-remission therapies. PERSPECTIVES: It is expected that future
      studies will provide more detailed information regarding either the normal ALL1
      function and/or the leukemogenic effect of ALL1 alterations, together with a
      better definition of the prognostic relevance of the hybrid proteins formed by
      this gene at diagnosis and during remission of disease.

PMID- 9592987
TI  - Prognostic factors and scoring systems in myelodysplastic syndromes.
AB  - BACKGROUND AND OBJECTIVE: Great prognostic heterogeneity complicates therapy
      planning and a correct evaluation of clinical trials in myelodysplastic syndromes
      (MDS). Thus, the development of a prognostic classification of MDS is of major
      clinical relevance, especially when the advanced age of most patients and the
      aggressiveness of the curative treatment modalities currently available are
      considered. This review summarizes the results of different studies focusing on
      prognostic factors in MDS and deals with the pros and cons of prognostic scoring
      systems that have been recently developed. It also discusses the prognostic
      factors of particular subtypes of patients and those isolated with certain
      treatment options. EVIDENCE AND INFORMATION SOURCES: The authors of the present
      review have been working in different areas of the field of MDS for several
      years, have contributed original papers on the prognostic factors and therapy of
      these disorders, and have taken part in the recent International MDS Risk
      Analysis Workshop that has resulted in the development of the International
      Prognostic Scoring System (IPSS) for MDS. STATE OF THE ART AND PERSPECTIVES: The
      percentage of marrow blasts, cytogenetic pattern and number and degree of
      cytopenias are the most powerful prognostic indicators in MDS. Although some
      limitations are evident, the recently developed scoring systems, and particularly
      the IPSS, are extremely useful for predicting survival and acute leukemic risk in
      individuals with MDS and should be incorporated to the design and analysis of
      therapeutic trials in these disorders. A risk-adapted treatment strategy is now
      possible and highly recommended for MDS patients.

PMID- 9592988
TI  - Persistent polyclonal B lymphocytosis with multiple bcl-2/IgH rearrangements: a
      benign disorder.
AB  - The appearance of a chronic B lymphocytosis is usually associated with the
      existence of an underlying monoclonal malignant condition. However, a few cases
      of persistent polyclonal B cell lymphocytosis (PPBL), presented in young
      asymptomatic women with an uneventful course, have been reported in recent years.
      In these PPBL cases, since the lymphocytes usually display an anomalous
      morphology, a false diagnosis of a neoplastic chronic lymphoproliferative
      syndrome can be easily made. We report a typical case of PPBL that presents
      multiple bcl-2 rearrangements, the typical finding of follicular lymphomas. A
      review of different causes of benign non neoplastic lymphocytosis with special
      steadiness in changes in the lymphoid subsets will be made.

PMID- 9592989
TI  - Angiotropic lymphoma: a rare hematological malignancy.

PMID- 9592990
TI  - Prevalence of phenotypic activated protein C resistance (APCR) in venous
      thromboembolic patients.
AB  - Until the discovery of activated protein C resistance (APCR), less than 10% of
      patients with venous thromboembolism (VT) showed defects in proteins involved in
      the inhibition of coagulation. APCR is caused by a single point mutation in the
      factor V gene, and it is accepted that APCR is associated with an increased risk
      for VT. In this work, we studied the prevalence of APCR in venous thromboembolic
      patients and found it to be 10.5% compared with 4.5% in controls (p = 0.105).

PMID- 9592991
TI  - Incidence and clinical manifestations of activated protein C resistance and
      factor V Leiden in young patients with venous thromboembolic disease in Spain.
AB  - In order to evaluate the actual incidence and clinical repercussion of activated
      protein C resistance (APCR) in our area, we performed a coagulation and
      thrombophillic study on 65 young patients diagnosed with deep vein thrombosis and
      53 controls. Family and genetic study was carried out in APC-resistant patients.
      We found APCR in 26.15% of patients and the 77.7% of these and their relative
      were heterozygous for factor V Leiden. There's a clear relationship between
      phenotype APCR and thrombosis, and also between factor V Leiden and thrombosis.

PMID- 9592992
TI  - Atypical microangiopathy in a patient treated with ticlopidine.
AB  - Microangiopathies are rare complications during treatments with ticlopidine. We
      describe an atypical microangiopathy, affecting almost exclusively myocardium,
      and thrombocytopenia, shortly after onset of ticlopidine. The patient died a few
      days after. Autopsy showed no bleedings or large thrombi in most organs, but were
      compatible with microangiopathy in myocardial small vessels.

PMID- 9592993
TI  - Pulmonary mucosa-associated lymphoid tissue lymphoma and myasthenia gravis. A
      case report.
AB  - We describe a low-grade, MALT-lymphoma with multiple, unusually large opacities
      involving both the lungs in a woman suffering from myasthenia gravis. Unlike
      other autoimmune diseases, myasthenia gravis has never been associated with MALT
      lymphoma thus far. After cyclophosphamide treatment, a complete detersion of the
      pulmonary opacities was obtained.

PMID- 9592994
TI  - Mantle cell lymphoma with amyotrophic lateral sclerosis (motor neuron disease)
AB  - We describe a previously unreported case of mantle cell lymphoma (MCL) associated
      to amyotrophic lateral sclerosis (ALS) in a 63-year-old woman with a 1-year
      history of weakness of arm and leg muscles. The both molecular-genetic and flow
      cytometry analysis of lymphocytes of peripheral blood (PB) demonstrated leukemic
      phase of MCL.

PMID- 9592995
TI  - Pathologic rupture of the spleen as the initial manifestation of acute
      lymphoblastic leukemia: an additional case.
AB  - Pathological rupture of the spleen (PRS) is a rare, but well known complication
      of some hematological malignancies. In a recent review of the literature,
      Giagounidis et al. Identified 136 cases of pathologic rupture of the spleen since
      1861. This number gives an idea of how seldom it occurs. In this review, 34% of
      the cases had occurred in acute leukemias, and 13% in acute lymphoblastic
      leukemias. In most cases, PRS occurs on the course of the disease. PRS as initial
      manifestation of ALL is a very rare feature: only six cases have been reported in
      the literature. Before now, in our hospital, we had only seen one case of a
      patient suffering from chronic myelomonocytic leukemia who presented splenic
      rupture as the initial manifestation of this disease. We now describe the seventh
      case, to our knowledge, of acute lymphoblastic leukemia presenting as pathologic
      splenic rupture.

PMID- 9592996
TI  - Evaluation of a live attenuated recombinant virus RAV 9395 as a herpes simplex
      virus type 2 vaccine in guinea pigs.
AB  - Recombinant virus RAV 9395 was constructed by deleting both copies of the
      gamma(1)34.5 gene, and the UL55 and UL56 open reading frames from herpes simplex
      virus type 2 (HSV-2) strain G. The potential use of RAV 9395 as an HSV-2 vaccine
      was investigated by evaluating the ability of RAV 9395 to protect guinea pigs
      from severe disease by HSV-2(G) challenge. RAV 9395 administered intramuscularly
      reduced both lesion development and severity in a dose-dependent manner in guinea
      pigs challenged with HSV-2(G). The frequency of reactivation of RAV 9395 from
      explanted dorsal root ganglia was low compared with that of HSV-2(G).
      Immunization with RAV 9395 at doses of 1 x 10(5) pfu and above generally
      precluded the establishment of latency by the challenge virus. The results
      presented in this report lend support for the development of genetically
      engineered live HSV vaccines.

PMID- 9592997
TI  - Long-term immunity and protection against herpes simplex virus type 2 in the
      murine female genital tract after mucosal but not systemic immunization.
AB  - The degree and duration of immunity against herpes simplex virus type 2 (HSV-2)
      infection of the female genital tract were assessed after intranasal (i.nl.) or
      intraperitoneal (i.p.) immunization with a recombinant adenovirus vector
      expressing HSV glycoprotein B (AdgB8). After intravaginal HSV-2 challenge,
      control mice rapidly developed disease and displayed high virus titers in vaginal
      washes. In contrast, virus titers decreased significantly and at similar rates in
      i.nl. and i.p. immunized mice and by day 7 were undetectable in vaginal wash
      samples. Assessment of genital pathology and survival showed that only i.nl.
      immunization provided long-term protection. Examination of antibody-secreting
      cells (ASCs) during the decline in vaginal virus titers revealed that gB-specific
      IgA ASCs were only observed in the genital tissues of i.nl. immunized mice. These
      results indicate that mucosal immunization provides a high and long-lasting level
      of immunity from sexually transmitted viral infections of the female genital
      tract.

PMID- 9592998
TI  - Intragenic variability of human cytomegalovirus glycoprotein B in clinical
      strains.
AB  - Human cytomegalovirus (HCMV) strains can be classified into four glycoprotein B
      (gB) genotypes, and there has been evidence of differences in viral virulence. In
      this study, intragenic variability of HCMV gB strains was analyzed. The gB gene
      was amplified by nested polymerase chain reaction using samples from
      immunosuppressed patients. The genotype of fragments corresponding to the
      cleavage site of gB was determined by restriction fragment analysis; fragments
      corresponding to the N- and C-termini (gBn and gBc) were sequenced and compared
      with published sequences. At the cleavage site, the four known genotypes were
      found. Typing revealed four major genotypes at the N-terminus and two at the C
      terminus. In 22 of 44 strains, the gB type determined at the cleavage site was
      different from the gBn or gBc type (or either), indicating that intragenic
      variability within the gB gene occurs frequently.

PMID- 9592999
TI  - Human cytomegalovirus in blood of immunocompetent persons during primary
      infection: prognostic implications for pregnancy.
AB  - Human cytomegalovirus (HCMV) was investigated in peripheral blood leukocytes
      (PBL) of 52 immunocompetent patients (40 pregnant women) with primary HCMV
      infection by quantitative determination of pp65 antigenemia, viremia, and
      leukoDNAemia. pp65 antigenemia was detected in 12 (57.1%) of 21, 4 (25%) of 16,
      and 0 of 10 patients examined 1, 2, and 3 months after onset, respectively.
      Viremia was detected in 5 (26.3%) of 19 patients during the first month only.
      LeukoDNAemia was detected in 20 of 20, 17 (89.5%) of 19, and 9 (47.3%) of 19
      patients tested 1, 2, and 3 months after onset, respectively. Four (26.6%) of 15
      patients were still DNAemia-positive at 4-6 months, whereas none were positive at
      >6 months. HCMV was not detected in PBL of 20 HCMV-immune donors or of 9
      seropositive subjects with recurrent infection. Virus levels were low by all
      assays and did not correlate with clinical course of infection, intrauterine
      transmission, or severity of outcome. Invasive procedures in the presence of
      maternal leukoDNAemia did not seem to interfere with vertical transmission of
      HCMV infection.

PMID- 9593000
TI  - Mutations in the cytomegalovirus UL97 gene associated with ganciclovir-resistant
      retinitis.
AB  - Vitreous from patients with cytomegalovirus (CMV) retinitis was studied in order
      to identify mutations in the CMV UL97 gene associated with clinical resistance to
      ganciclovir. Point mutations known to confer resistance (V460, I460, V594, and
      S595) were found in 6 of 11 study eyes. Rapid genetic screening by restriction
      enzyme analysis of viral DNA amplified directly from the vitreous was as
      effective as conventional sequencing in detecting these mutations. Repeat biopsy
      of 3 eyes revealed no change in the UL97 genotype. The UL97 genotype differed
      between eyes in 2 of 3 patients with bilateral, clinically resistant CMV
      retinitis. In summary, resistance mutations of the CMV UL97 gene are found in the
      vitreous of some, but not all, eyes with CMV retinitis that have not responded to
      ganciclovir therapy. These mutations can differ between eyes in patients with
      bilateral disease and can be rapidly detected using restriction digest analysis
      of polymerase chain reaction-amplified viral DNA.

PMID- 9593001
TI  - Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV
      maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in
      response to highly active antiretroviral therapy.
AB  - The suppression of human immunodeficiency virus (HIV) replication and elevation
      in CD4 cells observed with protease inhibitor combination regimens known as HAART
      (highly active antiretroviral therapy) may allow AIDS patients to undergo an
      immune recovery that allows them to suppress the progression of cytomegalovirus
      (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis
      in whom CMV-specific maintenance therapy was discontinued were studied. Median
      CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation
      of anti-CMV therapy. While a median 1.1 log10 drop in plasma HIV-1 RNA was
      obtained between starting HAART and withdrawal of maintenance therapy for CMV,
      only 3 of 11 patients maintained plasma HIV RNA below the limits of detection.
      Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur
      in any of the patients observed for a median of 156 days (range, 92-558).

PMID- 9593002
TI  - Association between cytomegalovirus seroconversion and upper genital tract
      infection among women attending a sexually transmitted disease clinic: a
      prospective study.
AB  - To study relationships between acquisition of cytomegalovirus (CMV), sexual
      activity, and sexually transmitted diseases, 245 CMV-seronegative women were
      followed (median, 23 months) in a sexually transmitted disease clinic between
      1980 and 1988. Thirty-six (15%) seroconverted (10%-12%/year). At entry,
      seroconverters were younger (P = .03), were younger at sexual debut (P = .004),
      and had more sex partners (P = .004) than non-seroconverters. During follow-up,
      seroconverters had more sex partners, had more new sex partners (P = .05 for
      each), and were more likely to have gonorrhea, chlamydia, or pelvic inflammatory
      disease. At seroconversion, Chlamydia trachomatis was isolated from cervix in
      14%, versus 3% of non-seroconverters (odds ratio [OR], 4.5; 95% confidence
      interval [CI], 1.3-14.9). Signs of upper genital tract infection were present in
      8% of seroconverters versus 2% of non-seroconverters (OR, 4.7; 95% CI, 1.0-21.8).
      Acquisition of CMV in these women was associated with sexual activity, sexually
      transmitted diseases, and signs of upper genital tract infection.

PMID- 9593003
TI  - Eradication of latent Epstein-Barr virus by hydroxyurea alters the growth
      transformed cell phenotype.
AB  - The hallmark of infection by human herpesviruses, life-long persistence in the
      host, is unaffected by current antiviral therapies effective against replication
      of virus. In vitro studies indicated that low concentrations of the
      ribonucleotide reductase inhibitor, hydroxyurea, completely eliminated Epstein
      Barr virus (EBV) episomes from latently infected Burkitt's lymphoma (BL) cell
      subsets, providing the first example of chemotherapeutic eradication of a latent
      herpesvirus from any cell population. Unlike parental EBV-positive BL cells,
      virus-free cell progeny from one treated cell line no longer exhibited the
      malignant phenotype in tumorigenicity assays. Hydroxyurea-treated primary B
      lymphocytes immortalized by EBV ceased to proliferate as episomes were lost. The
      altered growth phenotype of both BL cells and immortalized primary B cells
      suggests that latent EBV is an appropriate and accessible therapeutic target for
      treatment of some EBV-induced lymphoproliferations.

PMID- 9593004
TI  - Mother-to-infant transmission of GB virus C/hepatitis G virus: the role of high
      titered maternal viremia and mode of delivery.
AB  - To study mother-to-infant transmission of GB virus C/hepatitis G virus (GBV
      C/HGV), blood samples of infants born to carrier mothers were collected beginning
      3 months after birth and were tested for GBV-C/HGV RNA until 1 year of age. Of
      2046 mothers, 2.1% were positive for GBV-C/HGV RNA, and 25 of their infants were
      followed for a median of 12 months. Thirteen infants (52%) were viremic, and
      infection became persistent in all. Maternal GBV-C/HGV RNA levels of this group
      were >10(7) copies/mL. Nucleotide sequence comparison in 5 viremic mother-infant
      pairs revealed a homology of 93%-98.2%, and none delivered by elective cesarean
      section. In comparison, of the 12 uninfected infants' mothers, 10 had lower GBV
      C/HGV RNA levels (mean, 5 x 10(4) copies/mL), and the remaining 2 high-titered
      mothers had elective cesarean section. Thus, high-titered maternal viremia and
      mode of delivery are closely associated with the mother-to-infant transmission of
      GBV-C/HGV to infants, and the infection usually becomes persistent.

PMID- 9593005
TI  - Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus
      type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance.
AB  - Investigations were done to determine whether the replication kinetics of human
      immunodeficiency virus (HIV)-1 were altered when the virus acquired a set or
      subsets of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene
      conferring resistance to multiple dideoxynucleosides. In the absence of drugs,
      the replication rate of all infectious clones generated was comparable to that of
      wild type HIV-1. However, in the presence of zidovudine or didanosine, the
      comparative order for replication was HIV-1(62/75/77/116/151) > HIV-1(77/116/151)
      > HIV-1(75/77/116/151) approximately HIV-1(151), whereas that for drug resistance
      was HIV-1(75/77/116/151) > HIV-1(62/75/77/116/151) > or = HIV-1(77/116/151) > HIV
      1(151). The virologic features of these infectious mutants suggest that HIV-1
      develops drug resistance through one or more mutations, which, however, sacrifice
      replicative capability; then it finally acquires optimal replication competence
      by additional mutations when the multi-dideoxynucleoside-resistant mutant
      emerges.

PMID- 9593006
TI  - Distinct determinants of human immunodeficiency virus type 1 RNA and DNA loads in
      vaginal and cervical secretions.
AB  - The relationship between human immunodeficiency virus type 1 (HIV-1) viral RNA
      and proviral DNA load in vagina and cervix and that found in the plasma and
      peripheral blood mononuclear cells (PBMC) was investigated in 28 HIV-1-infected
      women. Of the patients, 64% had > or = 1 HIV-1 RNA-positive genital sample, while
      71% had > or = 1 DNA-positive sample. The higher the cervical HIV load, the more
      widespread was the virus in the genital tract. A strong correlation was found
      between viral RNA load in plasma and the genital tract, whereas the association
      between proviral DNA load in PBMC and the genital tract was less evident.
      Cervical HIV-1 DNA correlated with a viral RNA load > or = 50,000 copies/mL.
      Cervical HIV-1 RNA levels ranged from 10% to 100% of the plasma levels. Thus, a
      continuous transmission risk from untraumatized genital epithelium exists in the
      majority of HIV-1-infected women at all stages of infection.

PMID- 9593007
TI  - Measurement of human immunodeficiency virus type 1 plasma virus load based on
      reverse transcriptase (RT) activity: evidence of variabilities in levels of
      virion-associated RT.
AB  - Virus load based on levels of functional reverse transcriptase (RT) was measured
      in plasma from 50 human immunodeficiency virus (HIV) type 1-infected persons, in
      87 samples from 10 HIV-1 seroconversion panels, and in 100 uninfected persons by
      use of Amp-RT, an ultrasensitive RT assay. Of the 50 clinical samples, 38 (76%)
      were Amp-RT positive, while all uninfected controls were negative. Pearson's
      correlation coefficient of RNA and RT levels was .73 for all samples, .86 for
      seroconversion samples, and .49 for clinical samples. Calculated ratios of RT
      activity to virion RNA varied widely during both early and late stages of
      infection. Mean RT:RNA ratios in 8 seroconversion panels and in 12 (34.3%) of 35
      individual clinical samples were significantly lower than the ratio for a
      reference virus. However, ratios were stable in individual seroconversions over
      time. These data demonstrate that RT activity can be used to quantitate plasma
      virus load and provide evidence of different levels of virion-associated RT among
      HIV-1-infected persons.

PMID- 9593008
TI  - Immune responses to human immunodeficiency virus (HIV) type 1 induced by
      canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines
      in seronegative adults. NIAID AIDS Vaccine Evaluation Group.
AB  - A safety and immunogenicity trial was conducted in vaccinia-immune and vaccinia
      naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to
      receive 10(6) or 10(7) TCID50 of canarypox (ALVAC) vector expressing HIV-1MN
      gp160 or 10(5.5) TCID50 of ALVAC-rabies virus glycoprotein control at 0 and 1 or
      2 months and ALVAC-gp160 or 50 microg of HIV-1SF2 recombinant (r) gp120 in
      microfluidized emulsion at 9 and 12 months; others received rgp120 at 0, 1, 6,
      and 12 months. All vaccines were well-tolerated. Neither vaccinia-immune status
      before vaccination nor ALVAC dose affected HIV immune responses. HIV-1MN and HIV
      1SF2 neutralizing antibodies were detected more often (100%) in ALVAC
      gp160/rgp120 recipients than in recipients of ALVAC-gp160 (<65%) or rgp120 (89%)
      alone. ALVAC-gp160/rgp120 also elicited more frequent HIV V3-specific and fusion
      inhibition antibodies, antibody-dependent cellular cytotoxicity,
      lymphoproliferation, and cytotoxic CD8+ T cell activity than did either vaccine
      alone. Trials with ALVAC expressing additional HIV components and rgp120 are
      underway.

PMID- 9593009
TI  - Passive immunization of newborn rhesus macaques prevents oral simian
      immunodeficiency virus infection.
AB  - To determine if passively acquired antiviral antibodies modulate virus
      transmission and disease progression in human pediatric AIDS, the potential of
      pre- and postexposure passive immunization with hyperimmune serum to prevent oral
      simian immunodeficiency virus (SIV) infection or disease progression in newborn
      rhesus macaques was tested. Untreated neonates became infected after oral SIV
      inoculation and had high viremia, and most animals developed fatal AIDS within 3
      months. In contrast, SIV hyperimmune serum given subcutaneously prior to oral SIV
      inoculation protected 6 newborns against infection. When this SIV hyperimmune
      serum was given to 3 newborns 3 weeks after oral SIV inoculation, viremia was not
      reduced, and all 3 infants died within 3 months of age due to AIDS and immune
      complex disease. These results suggest that passively acquired antihuman
      immunodeficiency virus (HIV) IgG may decrease perinatal HIV transmission.
      However, anti-HIV IgG may not impart therapeutic benefit to infants with
      established HIV infection.

PMID- 9593010
TI  - Effect of rimantadine treatment on clinical manifestations and otologic
      complications in adults experimentally infected with influenza A (H1N1) virus.
AB  - Susceptible adults (n = 105) were enrolled into a randomized double-blind study
      of rimantadine treatment of experimental influenza A infection. Subjects were
      cloistered for 8 days and challenged with a rimantadine-sensitive strain of
      influenza A H1N1 virus at the end of the first day. Forty-eight hours after
      challenge and for 8 days, 54 subjects received placebo and 51 received
      rimantadine (100 mg orally, twice a day). Symptoms, signs, and pathophysiologies
      were monitored. Nine subjects were not infected. Seventeen subjects (38%) in the
      rimantadine and 26 (53%) in the placebo group became ill. A beneficial effect of
      rimantadine was documented for virus shedding, symptom load, and sinus pain.
      Rimantadine had no effect on nasal patency, mucociliary clearance, nasal signs,
      or on symptoms and signs of otologic complications. These results do not support
      a preventive effect of rimantadine on the development of otologic manifestations
      of influenza A infection in adults.

PMID- 9593011
TI  - Heterotypic protection against influenza by immunostimulating complexes is
      associated with the induction of cross-reactive cytotoxic T lymphocytes.
AB  - Influenza immunostimulating complexes (flu-ISCOMs) and a monovalent subvirion
      vaccine prepared with an H1N1 strain of influenza virus were compared in mice for
      immunogenicity and protection against challenge with homologous and heterotypic
      influenza viruses. flu-ISCOMs but not subvirion vaccine fully protected mice
      against homologous virus challenge after one immunization as assessed by
      measurement of virus lung titers. The improved protection induced by flu-ISCOMs
      was associated with a 10-fold higher prechallenge serum hemagglutination
      inhibition titer. Furthermore, only flu-ISCOMs fully protected mice against
      mortality and reduced morbidity following challenge with an influenza virus of
      the serologically distinct H2N2 subtype. This cross-protection correlated with
      the induction of virus cross-reactive cytotoxic T lymphocytes that recognized a
      known major histocompatibility class I (H2-Kd)-restricted epitope within the
      hemagglutinin of influenza virus that is conserved among the H1 and H2 influenza
      virus subtypes. flu-ISCOMs may offer significant advantages over current
      commercial formulations as an improved influenza vaccine.

PMID- 9593012
TI  - Activator protein-1 is the preferred transcription factor for cooperative
      interaction with nuclear factor-kappaB in respiratory syncytial virus-induced
      interleukin-8 gene expression in airway epithelium.
AB  - The role of "oxidant-sensitive" transcription factors activator protein (AP)-1,
      nuclear factor (NF)-kappaB, and NF-IL6 in respiratory syncytial virus (RSV)
      induced interleukin (IL)-8 gene expression in A549 epithelial cells was
      evaluated. RSV infection resulted in increased binding of each of these
      transcription factors. Transfection of A549 cells with plasmids containing serial
      truncations of the 5'-flanking region of the IL-8 gene revealed a positive
      cooperative effect of the binding sites for AP-1 and NF-kappaB. Mutation of
      either region markedly diminished responsiveness of the promoter to RSV. Mutation
      of the NF-IL6 site had minimal effect in the presence of intact binding sites for
      NF-kappaB and AP-1. The antioxidants NAC (N-acetylcysteine), DMSO, and DMPO (5,5
      dimethyl-1-pyrroline N-oxide) did not inhibit RSV-induced binding of NF-kappaB;
      however, binding of AP-1 and NF-IL6 was inhibited. These observations suggest
      that AP-1 may be the preferred transcription factor (over NF-IL6) for cooperative
      interaction with NF-kappaB in RSV-induced IL-8 production.

PMID- 9593013
TI  - Human leukocyte antigen class I- and class II-restricted cytotoxic T lymphocyte
      responses to measles antigens in immune adults.
AB  - The study of cytotoxic T cell (CTL) responses to measles polypeptides in persons
      with different HLA frequencies will provide information for the design of new
      vaccines. Peripheral blood mononuclear cells derived from African blacks and
      Caucasians were stimulated with measles virus-infected autologous cells and
      tested in a standard 51Cr-release assay against autologous B cells infected with
      vaccinia virus recombinants expressing measles virus antigens. The proportion of
      subjects who generated CTL to the fusion, hemagglutinin, and nucleoprotein
      antigens was 43%, 38%, and 28%, respectively. The use of HLA-mismatched targets
      showed killing to be restricted by both HLA class I and class II antigens,
      although CD8-mediated class I cytotoxicity predominated. Measles vaccine boosted
      CTL responses in subjects with low initial activity. These data suggest that the
      fusion and hemagglutinin proteins are important targets for the measles CTL
      response.

PMID- 9593014
TI  - Antibody persistence following preexposure regimens of cell-culture rabies
      vaccines: 10-year follow-up and proposal for a new booster policy.
AB  - Subjects (n = 312) received either the human diploid cell rabies vaccine (HDCV)
      or the purified Vero cell rabies vaccine (PVRV) according to either two-injection
      (days 0 and 28) or three-injection (days 0, 7, and 28) primary regimens. They
      received a booster injection at 1 year. Rabies antibody levels were measured
      after the primary series and the booster and then each year for the next 10
      years. The results confirm the superior long-term immunogenicity of the three
      injection over the two-injection protocol. HDCV and PVRV in three doses were
      equally immunogenic. A booster injection at 1 year provides long-term
      seroconversion (titer > or = 0.5 IU/mL). Antibody titers 2 weeks after the 1-year
      booster allowed prediction of long-term immunity. Good responders, with titers >
      or = 30 IU/mL, were protected for at least 10 years. An algorithm for
      differentiation between good responders and poor responders with respect to
      vaccine booster strategies is proposed.

PMID- 9593015
TI  - A comparative study of major histocompatibility complex and red blood cell
      antigen phenotypes as risk factors for recurrent urinary tract infections in
      women.
AB  - Recurrent urinary tract infections (RUTI) are a significant health problem for
      many women, and host characteristics that increase susceptibility are not
      completely defined. This study evaluated data from 99 patients to examine further
      the question of a possible association between major histocompatibility complex
      (MHC) or red blood cell (RBC) antigen phenotype and predisposition to RUTIs. MHC
      class I and II, ABO, and Lewis RBC phenotypes were determined serologically. The
      MHC class II phenotypes of 55 subjects were also determined by DNA polymerase
      chain reaction techniques. There were no significant differences in the
      proportions of HLA-A or -B antigen types between patients and controls, nor in
      the frequencies of serologically or DNA-defined HLA-DR or -DQ phenotypes. Patient
      ABO and Lewis RBC phenotypes were not statistically different than those for
      controls. Thus, the overall risk for women to develop RUTIs does not appear to be
      associated with any single HLA, ABO, or Lewis phenotype.

PMID- 9593017
TI  - Genomic diversity among Streptococcus agalactiae isolates detected by a
      degenerate oligonucleotide-primed amplification assay.
AB  - A random-amplified polymorphic DNA assay using partially degenerate
      oligonucleotides as primers was used for the characterization of 78
      epidemiologically related and unrelated clinical isolates of Streptococcus
      agalactiae belonging to different serotypes. Thirty distinct amplification
      profiles were obtained among 52 unrelated S. agalactiae isolates assigned to nine
      groups by serotyping (including 3 nontypeable strains), uncovering the extent of
      genomic heterogeneity existent within serotypes. This method was particularly
      useful in providing evidence for or against vertical transmission of a given
      clone of this microorganism, as well as for relapsing or reinfection in related
      cases, and suggested clonal relatedness between unrelated S. agalactiae isolates
      associated with some invasive infections. Thus, this simple methodology
      represents a suitable tool for the epidemiologic study of S. agalactiae
      infections.

PMID- 9593016
TI  - Correlation of antibiotic-induced endotoxin release and cytokine production in
      Escherichia coli-inoculated mouse whole blood ex vivo.
AB  - Escherichia coli were incubated in mouse whole blood ex vivo supplemented with
      beta-lactam antibiotics that possessed preferential affinities for penicillin
      binding proteins (PBPs). After 4 h, viable bacteria were undetectable in the
      presence of any of the 3 antibiotics tested, whereas significant increases in
      colony-forming units were detected in samples not treated with antibiotics.
      Differential levels of endotoxin in platelet-rich plasma were detected using the
      limulus amebocyte lysate assay, according to differential antibiotic affinities
      for the various PBPs. Levels of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) in antibiotic-treated cultures after 8 h of incubation
      correlated well with the levels of endotoxin at 4 h (r = .96, P < .0001 for TNF
      alpha; r = .91, P = .0002 for IL-6). These data indicate that differential
      affinities of beta-lactam antibiotics for PBPs affect both endotoxin and cytokine
      responses ex vivo in mouse blood and correlate with in vivo protective efficacy
      of these antibiotics in gram-negative experimental models.

PMID- 9593018
TI  - Identification of Leptospira species in the pathogenesis of uveitis and
      determination of clinical ocular characteristics in south India.
AB  - Uveitis is considered a rare complication of leptospirosis. This report describes
      an epidemic of uveitis among patients with leptospirosis and provides data, using
      polymerase chain reaction (PCR) amplification of Leptospira DNA, that the
      pathogenesis is associated with anterior chamber spirochetes. Forty-six uveitis
      patients, 49 uveitis controls, and 54 cataract controls were enrolled at Aravind
      Eye Hospital (Madurai, India). Leptospiral DNA was detected by PCR of aqueous
      humor; serum antibody titers were determined by ELISA and microagglutination
      (MAT). Thirty-seven uveitis patients (80%) demonstrated leptospiral DNA compared
      with 5 controls (8%; P < .001). Thirty-three uveitis patients (72%) had positive
      serology compared with 10 uveitis controls (20%) and 13 cataract controls (24%; P
      < .001). This report describes the largest cluster of patients with leptospiral
      uveitis and identifies six clinical characteristics that provide a diagnostic
      profile for leptospiral uveitis. This profile will be important for determining
      treatment regimens in countries where PCR and MAT are not available.

PMID- 9593019
TI  - Evidence of systemic dissemination of Chlamydia pneumoniae via macrophages in the
      mouse.
AB  - Chlamydia pneumoniae has been postulated to cause systemic disease by infection
      of monocytes/macrophages and spread via the blood or lymphatics. To investigate
      how C. pneumoniae disseminates, the ability of the organism to infect murine
      macrophages in vivo and whether infection can be transferred via macrophages were
      determined. C. pneumoniae was detected by direct plating, isolation, and
      polymerase chain reaction in alveolar macrophages from intranasally inoculated
      mice and peritoneal macrophages from intraperitoneally inoculated mice. C.
      pneumoniae were also detected in peripheral blood mononuclear cells, but not
      plasma, of intranasally and intraperitoneally inoculated mice. When alveolar or
      peritoneal macrophages were adoptively transferred by intraperitoneal injection
      from infected to uninfected mice, C. pneumoniae DNA was detected by polymerase
      chain reaction in lung, thymus, spleen, and/or abdominal lymph nodes. These
      results demonstrate the ability of C. pneumoniae to infect macrophages in vivo
      and to disseminate systemically via infected macrophages by hematogenous and
      lymphatic routes.

PMID- 9593020
TI  - Inhibition of Chlamydia pneumoniae replication in HEp-2 cells by interferon
      gamma: role of tryptophan catabolism.
AB  - Interferon-gamma (IFN-gamma) induces tryptophan catabolism in HEp-2 cells,
      possibly via stimulation of host cell indoleamine-2,3-dioxygenase activity, in a
      dose-dependent (12.5-1600 U/mL) fashion after 24 h, resulting in a 99% conversion
      to its metabolites at 1600 U/mL. Replication of Chlamydia pneumoniae isolates A
      03 and BAL-16 was inhibited in HEp-2 cells following treatment with 50 and 100
      U/mL IFN-gamma, respectively; however, addition of excess L-tryptophan (200
      microg/mL) to monolayers infected with C. pneumoniae resulted in unrestricted
      growth of both isolates up to 1600 U/mL IFN-gamma. C. pneumoniae could be
      recovered from IFN-gamma-treated monolayers, indicating the potential for this
      bacterium to undergo an altered life cycle, in vitro, analogous to that described
      in detail for Chlamydia trachomatis. The ability of C. pneumoniae to persist in
      host tissue despite an immunologic response would be an important attribute in
      order to cause or exacerbate chronic infections.

PMID- 9593021
TI  - The in vitro induction of human immunodeficiency virus (HIV) replication in
      purified protein derivative-positive HIV-infected persons by recall antigen
      response to Mycobacterium tuberculosis is the result of a balance of the effects
      of endogenous interleukin-2 and proinflammatory and antiinflammatory cytokines.
AB  - Coinfection with Mycobacterium tuberculosis and human immunodeficiency virus
      (HIV) is a serious problem, particularly in developing countries. Recently, M.
      tuberculosis and purified protein derivative (PPD) were demonstrated to induce
      HIV replication in CD8 T cell-depleted peripheral blood mononuclear cells from
      HIV-positive, PPD-positive persons but not in cells from PPD-negative persons.
      The role of endogenous and exogenous cytokines in modulating M. tuberculosis
      induced HIV replication was evaluated. M. tuberculosis-induced HIV replication
      decreased following simultaneous inhibition of endogenous interleukin (IL)-2, IL
      1beta, and tumor necrosis factor-alpha by the addition of soluble receptors and
      receptor antagonists or following exogenous IL-10 and transforming growth factor
      (TGF)-beta. In contrast, neutralization of endogenous IL-10 and TGF-beta
      augmented M. tuberculosis-induced HIV replication by increasing cellular
      activation. Thus, the balance between IL-2 and proinflammatory and
      antiinflammatory cytokines plays a major role in M. tuberculosis-induced
      replication of HIV.

PMID- 9593022
TI  - A cloned antigen (recombinant K39) of Leishmania chagasi diagnostic for visceral
      leishmaniasis in human immunodeficiency virus type 1 patients and a prognostic
      indicator for monitoring patients undergoing drug therapy.
AB  - Serologic assays using crude antigens for the diagnosis of visceral leishmaniasis
      in human immunodeficiency virus type 1 (HIV)-seropositive patients have been
      shown to lack sensitivity and specificity, particularly in AIDS patients.
      Antibodies to a cloned antigen, recombinant (r) K39, of Leishmania chagasi are
      specific for members of the Leishmania donovani complex and have been shown to
      indicate active disease in immunocompetent persons. This study demonstrated that
      antibodies to rK39 were also detectable in HIV-seropositive patients coinfected
      with Leishmania infantum. Furthermore, the rK39 ELISA was more sensitive than an
      IFA for detecting L. infantum infections in patients with AIDS. In addition,
      antibody titers to rK39 in HIV-negative patients infected with L. infantum or L.
      chagasi declined during treatment with meglumine antimoniate or liposomal
      amphotericin B. In contrast, most patients who clinically relapsed showed
      increased antibody titers to rK39. These data demonstrate the diagnostic and
      prognostic utility of rK39 in detecting active visceral leishmaniasis.

PMID- 9593023
TI  - Naive human T cells develop into Th1 or Th0 effectors and exhibit cytotoxicity
      early after stimulation with Leishmania-infected macrophages.
AB  - Studies of human disease suggest that naturally acquired immunity is the
      predominant outcome of Leishmania infection. Normally protective immune
      mechanisms activated during asymptomatic or self-healing infections may be
      minimal in patients who develop disease. To explore early immune responses, an in
      vitro model of human Leishmania infection was developed in which naive T cells
      were sensitized with Leishmania-infected macrophages. An analysis of Leishmania
      specific cytokine production by these T cell lines revealed that most individuals
      developed Th1 or Th0 responses early after infection. Infected macrophages from
      Th1 responders produced interleukin-12. Th0 responders who produced little or no
      endogenous interleukin-12 could be converted to the Th1 phenotype by addition of
      interleukin-12 during priming. Finally, infection-sensitized T cells specifically
      lysed Leishmania-infected macrophages. Thus, this in vitro model system can be
      used to delineate protective human immune responses against Leishmania induced
      early after infection.

PMID- 9593024
TI  - Field trial of a vaccine against New World cutaneous leishmaniasis in an at-risk
      child population: safety, immunogenicity, and efficacy during the first 12 months
      of follow-up.
AB  - The safety, immunogenicity, and efficacy of a vaccine against cutaneous
      leishmaniasis in rural Ecuadorian children was assessed in a randomized,
      controlled, double-blinded study. Vaccine group subjects received 2 intradermal
      doses of a whole, killed promastigote vaccine cocktail plus bacille Calmette
      Guerin (BCG) adjuvant. Control subjects got 2 doses of BCG only. The subjects who
      received both vaccination doses, 438 in the vaccine group (79.3%) and 406 in the
      control group (83.4%), were followed for 12 months. No serious adverse side
      effects were identified in either group. Significantly more vaccine group
      subjects than controls converted to a positive Montenegro skin test (85.1% vs.
      20.1%; chi2 = 279; P < .001). The incidence of cutaneous leishmaniasis was
      significantly reduced in the vaccine compared with the control group (2.1% vs.
      7.6%; chi2 = 8.95; P < .003). The protective efficacy of the vaccine was 72.9%
      (95% confidence interval = 36.1%-88.5%).

PMID- 9593025
TI  - Mechanisms that reduce transmission of Plasmodium falciparum malaria in
      semiimmune and nonimmune persons.
AB  - Transmission of Plasmodium falciparum can be reduced by immune factors present in
      the mosquito blood meal. Specific antibodies and white blood cells (WBCs) can
      interact with the sexual stages of the parasite inside the mosquito midgut. The
      relative contribution of serum factors and WBCs on transmission reduction in
      gametocyte carriers from an endemic area in Cameroon and in travelers with a
      first malaria experience was studied. Blood from these gametocyte carriers was
      fed to mosquitoes through membrane feeders after serum replacement, WBC
      depletion, or both. In most imported malaria cases, serum factors, WBCs, or both
      showed a significant effect on transmission reduction, while infectiousness of
      gametocyte carriers from Cameroon was reduced by humoral plasma factors only. In
      addition, the infectivity of gametocytes from semiimmune carriers was
      significantly lower compared with that of nonimmune carriers, and infectivity was
      independent of gametocyte density and the presence of WBCs or plasma factors (or
      both) in the blood meal.

PMID- 9593026
TI  - T and B cell reactivity to a 42-kDa protein is associated with human resistance
      to both schistosomiasis mansoni and haematobium.
AB  - Egyptian subjects living in areas endemic for Schistosoma mansoni or Schistosoma
      haematobium were selected on the basis of their apparent extremes of resistance
      or susceptibility to schistosomiasis and examined for T and B cell responses
      against the major electrophoretically resolved protein species from soluble adult
      worm extracts. A 42-kDa band was specifically recognized by a significant
      majority of subjects resistant to schistosomiasis. The 42-kDa species (p-42) from
      S. mansoni and S. haematobium were immunologically cross-reactive and induced
      significant protection in mice and hamsters against infection with cercariae.
      Amino acid sequence analysis of S. mansoni p-42 showed that it consists
      predominantly of glyceraldehyde 3-P dehydrogenase (G3PDH), which has been shown
      to be preferentially recognized by the sera of Brazilian subjects resistant to
      schistosomiasis mansoni. The present data extend the previous findings and imply
      that S. mansoni-derived G3PDH represents a target of protective T and B cell
      mediated antischistosomiasis immunity in humans.

PMID- 9593027
TI  - Albendazole for treatment and prophylaxis of microsporidiosis due to
      Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind
      controlled trial.
AB  - A double-blind placebo-controlled trial was conducted to assess the efficacy and
      safety of albendazole (400 mg twice daily for 3 weeks) for the treatment of
      Encephalitozoon intestinalis infection in patients with AIDS. Clearance of
      microsporidia from the intestinal tract was obtained in 4 of 4 patients in the
      albendazole group versus 0 of 4 in the control group (P = .01, one-sided Fisher's
      exact test) and was associated with significant clinical benefit. All 4 controls
      subsequently cleared microsporidia following open-labeled albendazole treatment.
      To investigate the effect of albendazole in preventing relapse, these 8 patients
      were then randomly assigned to receive either albendazole (400 mg twice daily) or
      no treatment for the next 12 months. Albendazole significantly delayed the
      occurrence of relapse (P = .04, one-sided log-rank test). In human
      immunodeficiency virus-infected patients with E. intestinalis infection,
      albendazole has parasitologic and clinical efficacy and reduces the risk of
      relapse.

PMID- 9593028
TI  - Neonatal fulminant hepatitis B: structural and functional analysis of complete
      hepatitis B virus genomes from mother and infant.
AB  - Transmission of hepatitis B virus (HBV) from anti-hepatitis B e (anti-HBe)
      positive carrier mothers to their infants may result in neonatal fulminant
      hepatitis B (FHB). We investigated whether HBV variants with a particular DNA
      sequence and functional phenotype, responsible for FHB, are selected during
      transmission. Full-length HBV genomes from a mother-infant pair were completely
      sequenced and transfected into human hepatoma cells. The dominant neonatal and
      maternal HBV populations were nearly identical (homology 99.8%) and showed a
      precore stop codon mutation, T-1762 and A-1764 substitutions in the core promoter
      region, and pre-S2 start codon mutations. Cells transfected with variants from
      mother and child, compared with wild-type virus, synthesized and released a
      similar number or fewer HBV DNA-containing particles. In conclusion, no
      particular HBV strain emerged during neonatal FHB. In this case, a de novo
      infection with variants showing a defect in HBe antigen and pre-S2 protein
      synthesis but not a high replication competence probably contributed to the
      fulminant disease course.

PMID- 9593029
TI  - Identification of more than one mutation in the hepatitis B virus polymerase gene
      arising during prolonged lamivudine treatment.
AB  - Lamivudine has been shown to be a potent and nontoxic inhibitor of hepatitis B
      virus (HBV) replication in chronically infected patients. During prolonged
      treatment, drug resistance may develop, related to a mutation of Met to Val or
      Ile in the YM552DD motif of the HBV DNA polymerase gene. Analysis of the HBV DNA
      polymerase gene from 8 chronic hepatitis B patients with suspected resistance to
      lamivudine showed that in addition to a mutation in the YM552DD motif, a second
      mutation located in the B domain of this gene, a Leu528-to-Met528 change, was
      consistently and exclusively found in 4 patients showing the YV552DD motif. This
      suggests a functional or structural relationship between these domains. Since the
      presence of both the YI552DD and YV552DD motif sometimes preceded the exclusive
      presence of the YV552DD motif, we conclude that the YI552DD motif could occur as
      a temporal intermediate. After cessation of therapy, the wild type sequences
      reemerged.

PMID- 9593030
TI  - Effect on normal vaginal flora of three intravaginal microbicidal agents
      potentially active against human immunodeficiency virus type 1.
AB  - The effect on normal vaginal flora of three intravaginal microbicides potentially
      active against human immunodeficiency virus type 1 was examined. Volunteers
      received dextrin sulfate (D2S), nonoxynol-9 (N-9), or docusate sodium in separate
      placebo-controlled studies. High vaginal swabs were obtained for bacterial
      culture before and after microbicide application. D2S did not affect the vaginal
      flora. However, lactobacilli decreased by > or = 10(2) cfu/mL in 9 (56%) of 16
      women given N-9 and in 5 (63%) of 8 women given docusate sodium. Women using N-9
      were also significantly more likely to become colonized abnormally (usually with
      aerobic gram-negative rods) than were those using placebo, as were women using
      docusate sodium. Women with reduced lactobacilli were less likely to regain
      normal flora than were those whose lactobacilli were unaffected. However,
      coliform colonization occurred whether lactobacilli produced H2O2 or not.
      Continuous use of N-9 could induce susceptibility to urinary and gynecological
      infection. It is essential that potential microbicides are examined for activity
      against normal vaginal flora.

PMID- 9593031
TI  - Infection of cells with varicella-zoster virus down-regulates surface expression
      of class I major histocompatibility complex antigens.
AB  - In vitro assays indicate that both major histocompatibility complex (MHC) class I
      and II-restricted cytotoxic T lymphocytes are important for recognition of
      varicella-zoster virus (VZV)-infected cells. This study demonstrates that
      infection of human fibroblasts with wild-type or recombinant-derived strain Oka
      VZV results in down-regulation of surface expression of class I MHC heavy chains.
      Radioactive labeling of infected cells indicated that the amount of newly
      synthesized class I antigen was similar in uninfected and VZV-infected cells. In
      addition, immunoblotting showed that the amount of total cellular class I MHC
      heavy chains was unaffected by VZV infection. These results suggest that the
      reduction of class I heavy chains on the surface of VZV-infected cells is due to
      a defect in posttranslational processing. The down-regulation of class I MHC
      antigens in VZV-infected cells may provide a mechanism for the virus to escape
      the host immune response.

PMID- 9593032
TI  - Safety and immunogenicity of low and high doses of trivalent live cold-adapted
      influenza vaccine administered intranasally as drops or spray to healthy
      children.
AB  - The safety and immunogenicity of various doses of trivalent cold-adapted
      influenza vaccine (CAIV-T) administered intranasally by drops or spray to
      children aged 18-71 months was examined. CAIV-T containing A/Johannesburg/33/94
      (H3N2), B/Panama/45/90, and A/Texas/36/91 (H1N1) was safe and well-tolerated. At
      the highest CAIV-T dose, 90%, 50%, and 16% of initially seronegative subjects
      seroconverted to the H3N2, B, and H1N1 antigens, respectively. The lower
      immunologic response to the H1N1 vaccine strain compared with the other strains
      was associated with a low frequency of H1N1 shedding. No statistically
      significant differences in reactogenicity or immunogenicity were detected between
      subjects who received CAIV-T by drops or spray. In conclusion, this CAIV-T was
      safe and induced acceptable immunologic responses to 2 of the 3 vaccine strains.
      Studies are needed to confirm previous observations that receipt of two doses of
      this vaccine results in immunologic responses that confer protection to all 3
      circulating influenza virus strains.

PMID- 9593033
TI  - In vivo expression of interleukin-1 receptors during various experimentally
      induced inflammatory conditions.
AB  - Systemically administered interleukin-1 (IL-1) has been shown to preferentially
      bind to IL-1 receptors (IL-1Rs) in inflammation. Using radiolabeled IL-1alpha and
      molecular methods to assess gene expression for these receptors, the in vivo
      behavior of these receptors was investigated in a number of experimental
      inflammatory conditions. The uptake of 125I-labeled IL-1alpha in inflammatory
      foci significantly correlated with the mRNA expression for the type I and type II
      IL-1Rs (P < .05). Type II IL-1R mRNA showed a greater increase in expression than
      type I IL-1R mRNA. In neutropenic mice, inflammatory lesions, which are devoid of
      granulocytes, significantly lower 125I-labeled IL-1alpha uptake (P < .001), and
      type II IL-1R mRNA expression (P < .005) was found. Thus, there is strong up
      regulation of IL-1Rs at sites of focal inflammation. Of interest, this mainly
      involved the type II IL-1R on granulocytes, which is not involved in signal
      transduction.

PMID- 9593034
TI  - Posttranscriptional down-regulation of tumor necrosis factor-alpha and
      interleukin-1beta production in acute meningococcal infections.
AB  - The regulation of tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL
      1beta) production was studied in patients with meningococcal disease. Circulating
      TNF and IL-1beta normalized within 1 day. TNF mRNA and IL-1beta mRNA in white
      blood cells decreased over 3-4 days. During the acute stage, TNF and IL-1beta
      production in stimulated whole blood cultures was down-regulated. After 4-5 days,
      this production was restored. The down-regulation was unlikely to be caused by
      circulating IL-6 and IL-10, as these cytokines normalized within 2-3 days. TNF
      mRNA in stimulated cultures during the acute stage, with down-regulated
      production, did not differ from that at recovery, with restored production. In
      contrast, the down-regulated production of IL-1beta was associated with
      significantly lower IL-1beta mRNA levels. Thus, TNF and IL-1beta production are
      differentially regulated. Whereas TNF production is regulated
      posttranscriptionally, IL-1beta production is also regulated at the mRNA level.

PMID- 9593035
TI  - A prolonged outbreak of Shigella sonnei infections in traditionally observant
      Jewish communities in North America caused by a molecularly distinct bacterial
      subtype.
AB  - During 1994-1996, Shigella sonnei outbreaks occurred in 8 North American
      traditionally observant Jewish communities. These communities remain relatively
      separate from neighboring populations while maintaining close contact by travel
      with coreligionists in other cities. Epidemiologic investigations suggested
      community-to-community transmission via travel. Outbreak-related and control
      isolates of S. sonnei from each city were subtyped by pulsed-field gel
      electrophoresis (PFGE) to confirm an epidemiologic linkage between outbreaks.
      Forty-three (94%) of 46 outbreak-related isolates had closely related PFGE
      patterns, constituting a single subtype; 33 (94%) of 35 control isolates
      demonstrated unrelated PFGE patterns. Several patterns differing by < or = 3
      bands were identified within the outbreak subtype; one of these accounted for 65%
      of outbreak isolates. Hence, a single subtype of S. sonnei caused an
      international outbreak involving 8 traditionally observant Jewish communities,
      but not neighboring populations, over a 2-year period, suggesting sustained
      propagation of the epidemic strain between communities.

PMID- 9593036
TI  - Enteroaggregative Escherichia coli strains as a cause of traveler's diarrhea: a
      case-control study.
AB  - To elucidate the importance of enteroaggregative Escherichia coli (EAggEC)
      strains as a cause of traveler's diarrhea in Spanish travelers, a prospective
      case-control 1:1 study was done in a university hospital clinic for travelers.
      EAggEC strains were isolated from 23 of 165 case-patients and from 4 of 165
      controls (P = .0003). In 16 patients, this was the only isolate recovered. Six of
      the EAggEC-positive isolates from the case-patients and 2 from the controls were
      positive for the enteroaggregative stable toxin type 1 gene. Other
      enteropathogens were also isolated. Shigella and enterotoxigenic E. coli strains
      showed significant differences between cases and controls (P = .0023 and P <
      .0001, respectively). Geographic distribution of the EAggEC strains was
      homogeneous, and the clinical symptom, secretory diarrhea, did not differ
      statistically with that for the enterotoxigenic E. coli strains. EAggEC strains
      are a cause of secretory diarrhea in Spaniards traveling to developing countries.

PMID- 9593037
TI  - Chemotactic factors in bronchial secretions of cystic fibrosis patients.
AB  - To understand chronic neutrophil attraction into cystic fibrosis airways, both
      global chemotactic activity and individual chemotactic factors were studied in
      bronchial secretions. Bronchial secretions of 8 cystic fibrosis patients,
      collected on the first day of admission for antibiotic treatment, showed a high
      chemotactic index (19.4 +/- 5.7, n = 8). Fractionation by gel filtration of
      bronchial secretions resulted in three chemotactic fractions. The first factor
      corresponded to interleukin-8, and the second activated neutrophils via the FMLP
      receptor. The third factor, which was of lower molecular weight, did not activate
      FMLP or leukotriene B4 receptors, and its nature is still under investigation.
      Treating patients with antibiotics reduced global chemotactic activity, mainly by
      reducing the activity due to stimulation of the FMLP receptor.

PMID- 9593038
TI  - The effect of lactic acid on mononuclear cell secretion of proinflammatory
      cytokines in response to group B streptococci.
AB  - This study found that lactate alone had a stimulatory effect (207.1 +/- 16.3%; P
      = .001) on tumor necrosis factor (TNF)-alpha production by human mononuclear
      cells with the most profound secretion being at pathologic concentrations of 4-8
      mM lactate. Furthermore, exposure of these mononuclear cells to group B
      streptococci (GBS, 10(5) cfu) resulted in TNF-alpha production of up to 621.1 +/-
      42% of control; the combination of lactic acid and GBS increased TNF-alpha
      production up to 1019.3 +/- 16.1% (P = .001). The combination of GBS and lactate
      also enhanced the secretion of interleukin (IL)-1beta and IL-6. Lactate in
      pathologic concentrations, therefore, likely enhances the secretion of these
      inflammatory mediators and contributes to septic shock and meningitis caused by
      GBS.

PMID- 9593039
TI  - Duration of tick attachment required for transmission of granulocytic
      ehrlichiosis.
AB  - Deer tick-transmitted pathogens such as Lyme disease spirochetes and babesiae
      appear to require a period of reactivation and replication during the tick's
      blood meal before it is able to infect a host. The duration of nymphal tick
      attachment that is required for transmission of the agent of human granulocytic
      ehrlichiosis (HGE) was determined by removing feeding ticks from mice at various
      time points. As with spirochetes and babesiae, ehrlichiae infected few mice when
      ticks were removed prior to 36 h of tick attachment. This "grace period" may
      serve as a modifying factor in the epidemiology of this newly emergent zoonosis
      and help physicians make informed decisions concerning management of tick bites
      in HGE-endemic areas.

PMID- 9593040
TI  - High prevalence of "Simkania Z," a novel Chlamydia-like bacterium, in infants
      with acute bronchiolitis.
AB  - The newly described microorganism "Simkania Z" ("Z"), an obligate intracellular,
      penicillin-resistant microorganism most closely related to the chlamydiae, has
      been associated with adult community-acquired pneumonia. The possible involvement
      of "Z" in bronchiolitis in infants was examined in a prospective study of 239
      infants with bronchiolitis and 78 controls. Other potential etiologic agents
      sought were respiratory syncytial virus (RSV), adenovirus, and cytomegalovirus.
      Evidence for the presence of "Z" in nasopharyngeal wash specimens (polymerase
      chain reaction and/or culture) was found in 25% of infants with bronchiolitis,
      while controls were all negative (P < .001). A serum IgA response to "Z"
      infection was detected by immunoperoxidase assay in 15% of infants with
      bronchiolitis versus 1.3% of controls (P < .001). Clinical findings were not
      different for infants with bronchiolitis associated with RSV alone, "Z" alone, or
      RSV and "Z" together. The high prevalence of "Z" in infants with bronchiolitis,
      often accompanied by an immune response, suggests a possible etiologic role of
      this agent in the disease.

PMID- 9593041
TI  - In vivo selection for a specific genotype of dihydropteroate synthetase of
      Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone
      treatment.
AB  - Plasmodium falciparum present in blood samples collected before and 3 weeks after
      treatment with either pyrimethamine-sulfadoxine or chlorproguanil-dapsone was
      analyzed for variants of the genes coding for the target enzymes of antifolate
      drugs, dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS).
      Fragments of the genes were amplified by polymerase chain reactions, and variants
      were identified by specific restriction endonuclease digestion. Treatment with
      either drug combination selected for the variants Ile51, Arg59, and Asn108 of
      DHFR, which have been associated with in vitro resistance to pyrimethamine and
      cycloguanil. The genotype Ser436, Gly437, and Glu540 of DHPS was selected by
      pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment, showing that
      a combination of these three variants is important for in vivo resistance to
      sulfadoxine in the area studied.

PMID- 9593042
TI  - Antigen-specific proliferation and interferon-gamma and interleukin-5 production
      are down-regulated during Schistosoma haematobium infection.
AB  - Antigen-specific cellular immune responses were examined in persons previously
      infected with Schistosoma haematobium and who were, 2 years after chemotherapy,
      either free from infection (n = 17) or reinfected (n = 20). Proliferation to
      adult worm antigen (AWA) was significantly higher in uninfected than in
      reinfected subjects (P = .02), whereas responses to soluble egg antigen (SEA)
      remained low in both groups. Interleukin (IL)-5 production in uninfected persons
      in response to AWA and SEA was higher than in infected subjects (P = .05 and P <
      .001, respectively), while IL-4 and IL-13 release was similar in the 2 groups.
      Levels of interferon-gamma to AWA and to SEA were inversely correlated with egg
      output (P = .03 and P = .02, respectively). These data indicate that the presence
      of schistosome infection leads to T cell proliferative hyporesponsiveness and
      that both typical Th1 and Th2 cytokines can be down-regulated by active
      infection.

PMID- 9593044
TI  - Direct isolation of DNA from patient stools for polymerase chain reaction
      detection of Cryptosporidium parvum.
AB  - Although polymerase chain reaction (PCR) can sensitively detect parasitic or
      other infections, its use with fecal samples is extremely limited, primarily
      because of the presence of substances that inhibit DNA extension. Here an
      improved protocol is reported for directly isolating DNA from aged or fresh
      formalin-fixed stools, which can then be used to detect Cryptosporidium parvum by
      nested PCR. This method is highly reproducible, sensitive, and specific. It
      detects <1 pg of C. parvum DNA in human stool, and there are no cross-reactions
      with other parasites commonly found there.

PMID- 9593043
TI  - The importance of leukotrienes in mast cell-mediated Toxoplasma gondii
      cytotoxicity.
AB  - Mast cells participate in the host defense against parasites. Mast cells release
      leukotrienes (LTs), potent 5-lipoxygenase (LO) products of arachidonic acid well
      known to be involved in the inflammatory process. After incubation with
      Toxoplasma gondii, mast cells were found to degranulate and release LTB4; this
      interaction damages the tachyzoites. This mast cell activity against the
      tachyzoites was inhibited by the 5-LO inhibitor A-63162 and the 5-LO-activating
      protein inhibitor MK-886 but not by the cyclooxygenase inhibitor indomethacin.
      Reactive oxygen species were not implicated in the mast cell-mediated
      toxoplasmacidal activity. The generation of LTs is important for mast cell
      secretion, and LTB4 released by mast cells and other inflammatory cells may be a
      key factor in the host defense against T. gondii.

PMID- 9593045
TI  - The spread and uptake pattern of intracerebrally administered oligonucleotides in
      nerve and glial cell populations of the rat brain.
AB  - The fate of 15-mer phosphorothioate-modified antisense oligonucleotides to c-fos
      was followed after their microinjection into rat brain. Using radiolabeled
      oligonucleotides, it was demonstrated that the bulk of the material stays in the
      injected region but that a minor part is transported with the projection pathways
      to regions far away from the site of injection. Using tetramethylrhodamine
      isothiocyanate (TRITC) labeling as well as fluorescein isothiocyanate (FITC)
      labeling, it was found that the oligonucleotides were taken up by a great number
      of cells within 30 minutes after the injection. A diffuse cytoplasmic staining
      and also nuclear staining were observed in these cells, which could be identified
      exclusively as neurons by double labeling for the neuron-specific protein NeuN.
      At later times (6, 24, and 48 hours), the appearance of the oligonucleotides
      changed gradually to a punctate cytoplasmic staining, which by electron
      microscopic analysis was shown to be caused by the presence of the
      oligonucleotides in intracellular vesicles. The pattern of intracellular
      fluorescence was changed when the oligonucleotides were injected together with
      the cationic lipid 1,2-bis(oleoyloxy)-3-(trimethylammonio)propane (DOTAP). A
      small number of astrocytes and microglial cells were found to be labeled by the
      oligonucleotides, but only at later times after the injection and exclusively in
      a punctate cytoplasmic manner. Thus, the uptake of oligonucleotides in the nerve
      and glial cell populations of the brain might involve different mechanisms, the
      one in the neurons appearing to be very rapid and potent.

PMID- 9593046
TI  - Rapid induction of Jak2 and Sp1 in T cells by phosphorothioate oligonucleotides.
AB  - Phosphorothioate-modified ODNs ([S]ODNs) are known to exert a variety of sequence
      independent effects that are mediated in part by rapid induction of the Sp1
      transcription factor. An unidentified tyrosine kinase was implicated in this Sp1
      induction. In the present study, antisense [S]ODNs, initially designed to target
      three signaling molecules in the prolactin (PRL)-responsive rat Nb2 T cell line
      rapidly elevated Jak2 tyrosine kinase and Sp1 protein levels. The [S]ODN-mediated
      elevation of Jak2 peaked (3-fold to 6.5-fold above controls) at 15 minutes and
      returned to basal levels by 1 hour, whereas elevation of Sp1 (about 2-fold above
      controls) peaked at 1 hour. The [S]ODN-mediated induction of Sp1, but not Jak2,
      was abrogated by AG 490, a Jak2-specific inhibitor. In the presence of submaximal
      doses of PRL (0.18-0.36 ng/ml), [S]ODN-mediated induction of Jak2 and Sp1 was
      sustained for 72 hours. Furthermore, the [S]ODNs alone significantly increased
      Nb2 cell growth and enhanced the growth stimulatory effects of PRL on these
      cells. In contrast, unmodified ODNs had no effect on Jak2 or Sp1 protein levels
      and did not stimulate Nb2 cell growth. In conclusion, [S]ODNs stimulate the
      coordinate induction of Jak2 and Sp1 and stimulate Nb2 T cell proliferation in a
      sequence-independent manner. The abrogation of Sp1 induction by AG 490 indicates
      that Jak2 tyrosine kinase is required for [S]ODN-mediated induction of Sp1 in
      these cells. These results may help to explain some of the nonspecific effects of
      [S]ODNs, particularly in cytokine-dependent immune cells.

PMID- 9593047
TI  - Biologic activity of oligonucleotides with polarity and anomeric center reversal.
AB  - Human papillomavirus (HPV) type 16 E6 and E7 inactivate the tumor suppressors p53
      and pRB, respectively. Both viral oncoproteins play important roles in
      maintaining the transformed phenotype of cells. In this study, we examine the
      effects of antisense oligodeoxynucleotides with polarity and anomeric center
      reversal (alpha/beta-ODNs). ODNs of the general structure
      5'alphaN3'3'NNN5'5'alphaN3'3'NNNN5'5'alphaN3+ ++'3'N5' were synthesized using
      phosphoramidite DNA chemistry. These alpha/beta-ODNs were complementary in
      sequence to regions flanking the start codons of HPV type 16 E6 and E7 genes. The
      anti-HPV type 16 alpha/beta-ODNs were able to form stable duplexes with their
      complementary RNA, which then serve as substrates for RNase H hydrolysis. Anti
      HPV type 16 alpha/beta-ODNs also specifically inhibited the growth of two
      cervical carcinoma cell lines, CaSki and SiHa, both of which harbor HPV type 16
      DNA. A decrease in E7 protein expression was also observed. Injection of nude
      mice with SiHa cells induces tumors. Treatment of these tumor-bearing mice with
      anti-HPV type 16 alpha/beta-ODNs led to substantially smaller tumors. These
      results show that alpha/beta-ODNs can exert antisense activities both in vitro
      and in vivo on the E6 and E7 genes of HPV type 16.

PMID- 9593048
TI  - Assessment of high-affinity hybridization, RNase H cleavage, and covalent linkage
      in translation arrest by antisense oligonucleotides.
AB  - Antisense oligonucleotides (ONs) are designed to hybridize target mRNA in a
      sequence-specific manner and inhibit gene expression by preventing translation,
      either by activation of RNase H or steric blockage of the ribosome complex.
      Second-generation ONs, which possess greater binding affinity for target RNA
      relative to the isosequential phosphodiester (PO) ONs, have been developed and
      include, among others, peptide nucleic acids (PNA) and N3' P5' phosphoramidate
      oligonucleotides (npONs). In the present study, PNA and npON derivatives were
      targeted to the coding portion of the complementary mRNA of the N protein of the
      vesicular stomatitis virus (VSV) in order to evaluate their ability to arrest
      translation in an in vitro rabbit reticulocyte lysate system. High-affinity
      hybridization of ONs lacking RNase H activity was not sufficient to block
      translation in this test system. Only antisense ONs acting via an RNase H
      mechanism or by steric hindrance through covalent attachment (via transplatin
      modification) to the target mRNA were found to definitively arrest translation in
      this study.

PMID- 9593049
TI  - An overview of progress in antisense therapeutics.

PMID- 9593050
TI  - Conformational preorganization, hydration, and nucleic acid duplex stability.

PMID- 9593051
TI  - How to design an antisense oligodeoxynucleotide experiment: a consensus approach.

PMID- 9593052
TI  - Molecular mechanisms of antisense drugs: RNase H.

PMID- 9593053
TI  - Mixed backbone oligonucleotides: improvement in oligonucleotide-induced toxicity
      in vivo.

PMID- 9593054
TI  - Cooperative antitumor effect of mixed backbone oligonucleotides targeting protein
      kinase A in combination with cytotoxic drugs or biologic agents.

PMID- 9593056
TI  - Utility of oligonucleotides as tools to study the function and regulation of 85
      kDa phospholipase A2.

PMID- 9593055
TI  - Antisense oligonucleotides as inhibitors of genes that regulate AP-1:
      pharmacology and clinical development.

PMID- 9593058
TI  - CRE-palindrome oligonucleotide as a transcription factor decoy and an inhibitor
      of tumor growth.

PMID- 9593057
TI  - Transcriptional regulation of the human proenkephalin gene by conformational
      switching: implications for decoy design.

PMID- 9593059
TI  - E2F decoy oligonucleotide for genetic engineering of vascular bypass grafts.

PMID- 9593060
TI  - Non-antisense oligonucleotide approaches for experimental treatment of
      glioblastoma.

PMID- 9593061
TI  - Therapeutic applications of CpG-containing oligodeoxynucleotides.

PMID- 9593062
TI  - Antioxidant diet preserves endothelium-dependent vasodilatation in resistance
      arteries of hypercholesterolemic rabbits exposed to environmental tobacco smoke.
AB  - Environmental tobacco smoke (ETS) has been shown to impair endothelium-dependent
      vasodilation in vitro. This study was performed to investigate the effect of ETS
      on acetylcholine (ACh)-mediated blood pressure changes in vivo. Seventeen New
      Zealand White rabbits were fed a cholesterol diet (0.3%) for 13 weeks. Ten
      animals were exposed to ETS for 6 h/day, and seven animals were not exposed to
      ETS (non-ETS). Four of the ETS and three of the non-ETS-exposed rabbits received
      an antioxidant vitamin diet before and during their cholesterol diet for 21
      weeks. Six rabbits served as healthy controls. To determine endothelium-dependent
      and independent blood pressure (BP) responses, BP was measured through a Tygon
      catheter, inserted into the right carotid artery at baseline and after each of
      three incremental intravenous doses of norepinephrine (NE; 1, 4, and 20
      microg/kg), ACh (3.3, 10, and 30 microg/kg), and nitroglycerin (NTG; 1, 10, and
      40 microg/kg). After NE, BP increases were significantly attenuated in the ETS
      group (p = 0.001) but not in animals receiving the antioxidant supplement. At
      both the middle and high ACh concentrations, ETS (p = 0.03 and p = 0.01,
      respectively) and hypercholesterolemia (p = 0.03 and p = 0.06, respectively)
      attenuated ACh-induced reductions in BP. At the highest ACh concentration,
      vitamins enhanced the reduction in BP (p = 0.002) and blocked the effect of ETS
      (p = 0.04). Neither ETS nor vitamins influenced NTG-induced decreases in BP. A
      combined antioxidant-vitamin diet can preserve endothelium-dependent
      vasodilatation in the hypercholesterolemic rabbit exposed to ETS.

PMID- 9593064
TI  - Effects of amlodipine once or twice daily on circadian blood pressure profile,
      myocardial hypertrophy, and beta-adrenergic signaling in transgenic hypertensive
      TGR(mREN2)27 rats.
AB  - The effects of amlodipine on blood pressure profiles, cardiac hypertrophy, and
      beta-adrenergic signal transduction were studied in transgenic hypertensive
      TGR(mREN2)27 rats (TGRs), which are characterized by an inverse circadian blood
      pressure rhythm. Cardiovascular parameters were monitored by radiotelemetry; beta
      adrenoceptor density and function were measured by radioligand binding and by
      determination of beta-adrenergic stimulation of adenylyl cyclase. Ventricular
      weight and the activity of cardiac sarcolemmal 5-nucleotidase were used as
      measures of hypertrophy. Acute i.p. injection of amlodipine (1, 3, 10 mg/kg body
      weight) either at 8:00 or at 20:00 h dose-dependently reduced blood pressure
      irrespective of the dosing time. For long-term treatment, TGRs were divided into
      three groups: untreated; amlodipine, once-daily, 5 mg/kg; and amlodipine, twice
      daily, 2.5 mg/kg. Both treatment schedules resulted in decreased 24 h means in
      systolic and diastolic blood pressure and a reduction in ventricular hypertrophy
      but had no effects on cardiac beta-adrenergic signaling. Once-daily dose of
      amlodipine at 8:00 h decreased blood pressure predominantly during the daily
      resting period of the rats, whereas twice-daily dosing induced a bimodal blood
      pressure pattern. However, even after 5 weeks of treatment, typical circadian
      profiles could not be observed with either treatment, indicating a short duration
      of action of amlodipine in rats. Thus it remains an open question whether
      pharmacologic normalization of the circadian blood pressure pattern in TGRs will
      more effectively reduce myocardial hypertrophy and restore beta-adrenergic
      signaling than a reduction in 24-h blood pressure per se.

PMID- 9593063
TI  - Divergent effects of angiotensin-converting enzyme inhibition and angiotensin II
      receptor antagonism on myocardial cellular proliferation and collagen deposition
      after myocardial infarction in rats.
AB  - There is mechanistic rationale to suggest differential effects of angiotensin
      converting enzyme (ACE) inhibition and angiotensin II type 1 (AT1)-receptor
      antagonism on ventricular remodeling after myocardial infarction (MI). We
      compared the effects of ACE inhibition, AT1-receptor antagonism, and their
      combination on post-MI ventricular remodeling in rats. We induced MI in 62 rats,
      which then received one of four treatments: (a) placebo; (b) the ACE inhibitor,
      enalapril; (c) the AT1-receptor antagonist, losartan; and (d) enalapril and
      losartan in combination. Two weeks after MI, we examined: (a) heart weight
      (HW)/body weight (BW) ratio; (b) nonmyocyte cellular proliferation in the
      noninfarct zone by using proliferating cell nuclear antigen staining; and (c)
      collagen content within the noninfarct zone. Placebo-treated, infarcted rats
      developed significant increases in HW/BW ratio (p < 0.001), left ventricular (LV)
      volume (p < 0.01), nonmyocyte cellular proliferation (p < 0.04), and collagen
      content (p < 0.01) compared with noninfarcted controls. Enalapril, losartan, and
      combination therapy limited the increase in HW/BW ratio (all p values <0.01 vs.
      placebo). Enalapril inhibited nonmyocyte proliferation (p < 0.01 vs. placebo),
      whereas losartan had a smaller effect (p = NS vs. placebo; p < 0.03 vs.
      enalapril); combined treatment also reduced nonmyocyte cellular proliferation but
      did not reach statistical significance (p = 0.08 vs. placebo). Enalapril and
      combination treatment significantly diminished collagen content (both p values
      <0.01 vs. placebo), whereas losartan did not. Thus, ACE inhibition and AT1
      receptor antagonism equally limited myocardial hypertrophy after MI in rats, but
      ACE inhibition more effectively prevented nonmyocyte cellular proliferation and
      collagen deposition in the noninfarcted myocardium. Combination therapy was no
      more effective than was ACE inhibition alone. These data suggest that the myocyte
      hypertrophic response after MI is strongly influenced by activation of the AT1
      receptor, whereas nonmyocyte cellular proliferation and collagen deposition
      result, in part, from mechanisms separate from AT1-receptor activation.

PMID- 9593065
TI  - Effects of ANF infusion on the renal responses to lower-body negative pressure in
      humans.
AB  - To investigate the role of atrial natriuretic factor (ANF) in renal responses to
      a decrease in central blood volume, we examined the effects of ANF infusion on
      renal function and hormones during prolonged lower-body negative pressure (LBNP).
      Ten healthy volunteers participated in two experimental sequences, each
      comprising a 120-min baseline period followed by the application of -20 mm Hg
      LBNP for 90 min. During one of the two sequences, ANF was infused throughout LBNP
      application at the constant rate of 2.5 ng/kg/min. Glomerular filtration rate
      (GFR) and effective renal plasma flow (ERPF) were measured by using inulin and p
      aminohippuric acid clearance techniques. LBNP induced a significant decrease in
      ERPF (534 +/- 28 to 457 +/- 26 ml/min; p < 0.05), GFR (120 +/- 2.5 to 112 +/- 2.5
      ml/min; p < or = 0.01), in urine excretion (12 +/- 0.9 to 5.6 +/- 0.5 ml/min; p <
      0.001), in sodium excretion (0.36 +/- 0.03 to 0.30 +/- 0.02 mmol/min; p < 0.05),
      and in plasma ANF (19 +/- 3 to 11 +/- 2 pg/ml; p = 0.001) concomitant with an
      increase in plasma renin activity (PRA; 0.48 +/- 0.09 to 0.87 +/- 0.16 ng/ml/h; p
      = 0.01) and of forearm vascular resistance (FVR; p < 0.05). The combination of
      ANF infusion with LBNP led to a slight increase in plasma ANF from baseline (from
      20 +/- 2 to 28 +/- 3 pg/ml; p < 0.05). Compared with values obtained during LBNP
      with saline vehicle infusion, values obtained during LBNP with ANF infusion were
      similar for ERPF (463 +/- 23 vs. 457 +/- 26 ml/min), for GFR (111 +/- 2 vs. 112
      +/- 2 ml/min), and for urine excretion (7 +/- 0.6 vs. 5.6 +/- 0.5 ml/min; p =
      0.07), but greater for fractional excretion of sodium (2.38 +/- 0.25% vs. 1.91 +/
      0.11%; p < 0.05) and FVR (p < 0.05), and smaller for PRA (0.49 +/- 0.1 vs. 0.87
      +/- 0.16 ng/ml/h; p < 0.01). These data show that ANF infusion attenuates the
      antinatriuretic effect of low-level LBNP and its PRA-increasing effects without
      altering renal hemodynamic responses to LBNP, although there is a decrease in the
      LBNP-induced forearm vasoconstriction. These results were obtained with plasma
      ANF levels slightly higher than those in baseline. They support the hypothesis
      that a decrease in ANF secretion might contribute to the antinatriuretic effect
      of LBNP.

PMID- 9593066
TI  - Effects of doxazosin and atenolol on atherothrombogenic risk profile in
      hypertensive middle-aged men.
AB  - The alpha-blockers prazosin and doxazosin reduce hypertriglyceridemia (HTG) and
      increase serum levels of high-density lipoprotein (HDL)-cholesterol, whereas beta
      blockers such as atenolol have the opposite effect. As HTG is associated with
      reduced fibrinolysis and hypercoagulability, we investigated the effects of
      doxazosin and atenolol on serum lipids and hemostatic factors in hypertensive men
      with an atherothrombogenic risk profile. The study was randomized and open, but
      blinded to investigator of biochemical results. Forty-five men (mean age, 44.5
      years) with central obesity [median body-mass index (BMI), 28 kg/m2] and moderate
      hypertension [median diastolic blood pressure (DBP), 104.5 mm Hg] were treated
      with atenolol (n = 22) or doxazosin (n = 23) for 22 weeks, after which changes in
      between-group differences from baseline were estimated. After intervention,
      significant between-group differences in favor of doxazosin were found: lower
      triglycerides (p = 0.008) and higher HDL cholesterol (p = 0.036); furthermore,
      improvement of fibrinolysis: lower plasminogen activator inhibitor-1 (PAI-1)
      activity (p = 0.012), higher tissue plasminogen activator (tPA) activity after
      venous occlusion (VO); and higher levels of serum D-dimer, both unstimulated (p =
      0.0016) and after VO (p = 0.0032). In addition, lower levels of serum
      testosterone were found in the atenolol group (p = 0.0016). A profile with
      reduced HTG, increased HDL cholesterol, and improved fibrinolysis was obtained
      with doxazosin when compared with atenolol. Furthermore, the observed decrease in
      serum testosterone on atenolol treatment would rather favor long-term treatment
      with doxazosin in this study population.

PMID- 9593067
TI  - Positive inotropic effects of the novel Na+-channel modulator BDF 9198 in human
      nonfailing and failing myocardium.
AB  - The aim of this study was to investigate the inotropic properties of the novel
      Na+-channel modulator BDF 9198 in human nonfailing and failing myocardium. For
      comparison the Na+-channel modulator BDF 9148, the beta-adrenoceptor-agonist
      isoprenaline, and calcium were studied. Concentration-response curves for BDF
      9198 (0.01-30 microM), BDF 9148 (0.01-30 microM), isoprenaline (0.001-1 microM),
      and calcium (1.8-15 mM) were obtained in electrically driven left ventricular
      human papillary muscle strips (1 Hz, 37 degrees C; dilated cardiomyopathy, NYHA
      IV, heart transplantation; nonfailing, donor hearts). Whereas isoprenaline was
      significantly less effective and less potent in increasing the force of
      contraction in failing human myocardium than in nonfailing myocardium (p < 0.01),
      BDF 9198 and BDF 9148 were (in NYHA IV) as effective as in nonfailing human
      tissue. In both tissues, BDF 9198 and BDF 9148 exerted similar positive inotropic
      effects as calcium, with the novel Na+-channel modulator BDF 9198 being more
      potent in increasing force of contraction than was the preceding agent BDF 9148.
      The potencies of both Na+-channel modulators, BDF 9198 and BDF 9148, were
      enhanced in human failing myocardium when compared with nonfailing myocardium. In
      summary, the novel Na+-channel modulator BDF 9198 increases force of contraction
      to the same extent as calcium and with a higher potency than BDF 9148. The
      sensitivity of failing human myocardium to Na+-channel modulators is increased
      when compared with nonfailing myocardium, which might be the result of an altered
      Na+ homeostasis in human heart failure.

PMID- 9593068
TI  - Influence of 0.1 or 0.2% cholesterol-enriched diets on the induction of
      atherosclerosis and aorta reactivity in vitro.
AB  - Current knowledge of atherogenesis is largely based on animal models of
      hypercholesterolemia, which rarely show changes similar to the lesions described
      in humans. We studied the influence of two low cholesterol-enriched diets on the
      development of anatomopathologic lesions and on the reactivity of the isolated
      aorta in rabbits. Compared with controls (rabbits fed a normal diet), a 0.1%
      cholesterol-enriched diet over a 6- or 9-month period produced increases of the 5
      hydroxytryptamine (5-HT)-induced contractile responses, as well as a decreases in
      acetylcholine (ACh)-induced relaxing response (endothelium-dependent, through the
      production of NO). Noradrenaline (NA)-induced contractions and relaxations
      elicited by sodium nitroprusside (SNP; endothelium independent) were not
      significantly modified. Because at 6 months, significant anatomopathologic
      intimal early lesions were not found, functional endothelial changes can explain
      such findings. There was a defect in NO synthesis, release, or diffusion; 5 HT,
      but not NA, may be responsible for inducing NO production. In 0.2% cholesterol
      fed rabbits at 4 and 12 weeks, increases of 5-HT- and NA-induced contractile
      responses were found. In both cases, there was a decrease of ACh-induced relaxing
      effect, whereas responses to SNP remained unchanged. Intimal early and advanced
      lesions were present at both the 4- and 12-week periods. These data suggest
      abnormalities of the NO system. The effects obtained with NA may be explained by
      a possible decrease of catechol-O-methyltransferase (COMT) or monoamine oxidase
      (MAO) activities or both or by decreased amine uptake. The extent to which NA may
      induce NO production is small, because changes in NA-induced contractions are
      verified only in the presence of significant alterations in the endothelium. The
      use of a 0.2% cholesterol diet for a short time may induce atherosclerotic
      lesions, whereas the 0.1% cholesterol diet for a 9-month period, besides being
      closer to the human diet, allows the detection of functional abnormalities before
      the evidence of structural lesions.

PMID- 9593069
TI  - Effects of the angiotensin II type-1 receptor antagonist ZD7155 on angiotensin II
      mediated regulation of renin secretion and renal renin gene expression, renal
      vasoconstriction, and blood pressure in rats.
AB  - Angiotensin II receptors have recently been subclassified as type-1 or type-2
      receptors. The in vitro and in vivo effects of blocking the angiotensin II type-1
      receptor with ZD7155, an angiotensin II type-1 selective receptor antagonist,
      have been studied in angiotensin II-mediated increases in cytosolic calcium in
      rat mesangial cells, in angiotensin II-induced renal and systemic
      vasoconstriction, and in angiotensin II-mediated regulation of renin secretion
      and renal renin gene expression. ZD7155 completely blocked the ability of
      angiotensin II to elicit an increase in free intracellular calcium concentrations
      in rat mesangial cells. In isolated perfused rat kidneys, ZD7155 completely
      abolished the angiotensin II-induced vasoconstriction and increased renin
      secretion to 700% of baseline levels. Furthermore, ZD7155 decreased systolic
      blood pressure by 16 mm Hg, increased plasma renin activity 3.7-fold, and
      stimulated renal renin gene expression 4.2-fold in Sprague-Dawley rats in vivo.
      Our results suggest that ZD7155 is a potent antagonist of the angiotensin II type
      1 receptor, which mediates angiotensin II-induced increases of free intracellular
      calcium concentrations in (e.g., renal mesangial cells), constriction of the
      renal and systemic vasculature, and inhibition of renin secretion and synthesis.

PMID- 9593070
TI  - Elucidating the mechanism of cesium-induced sustained monomorphic ventricular
      tachycardia in rabbits.
AB  - The mechanisms of sustained ventricular tachycardia (VT) induced by large
      cumulative dose of cesium chloride (Cs) remains unclear. Seven anesthetized
      rabbits were intravenously injected with Cs (1 mmol/kg) 3 times at 20-min
      intervals. The surface ECG and monophasic action potential of the left
      ventricular endocardium were simultaneously recorded. In another 12 rabbits,
      transmembrane action potentials of right ventricular muscles were recorded with
      glass microelectrodes. In experiments in vivo, sustained monomorphic VT was
      induced after the third injection of Cs, whereas the early afterdepolarization
      (EAD)-related nonsustained polymorphic VT was induced after the second injection.
      Overdrive pacing during the sustained VT resulted in postdrive acceleration. The
      pacing and recovery cycle lengths showed an inverse relation. In experiments in
      vitro, preparations were superfused with Tyrode's solution containing 7.5 mM Cs.
      Cs initially induced EADs. Additional exposure to Cs depolarized the membrane
      potential, which consequently attained threshold, producing spontaneous
      activities. Further exposure resulted in an induction of sustained rhythms that
      were accelerated by overdrive pacing. Our results indicate that the sustained
      rhythms at low membrane potential induced by a long exposure to Cs in vitro may
      underlie an electrophysiologic mechanism for the sustained VT induced after large
      cumulative dose of Cs in vivo.

PMID- 9593071
TI  - Autonomic effects of nicotine patch administration in habitual cigarette smokers:
      a double-blind, placebo-controlled study using spectral analysis of RR interval
      and systolic arterial pressure variabilities.
AB  - Nicotine patch administration is often used to sustain tobacco abstinence in
      smoking-cessation programs. There is some concern regarding safety issues, as a
      consequence of the sympathomimetic action of nicotine. We used spectral analysis
      of RR interval and (noninvasive) systolic arterial pressure (SAP) beat-by-beat
      variabilities in a crossover double-blind design to assess the autonomic effects
      of cigarette smoking, of transdermal nicotine, and of placebo. The study group
      consisted of 27 heavy smokers (age 43 +/- 2 years). The RR interval and its
      variability were significantly reduced in the smoking group, as compared with
      nicotine or placebo groups. The LF component of RR interval variability (in
      normalized units, nu), and the LF/HF ratio showed greatest values during smoking,
      as compared with placebo. Values of LF(RR) and LF/HF during nicotine patch
      treatment were slightly, but not significantly, greater than observed with
      placebo. No differences were observed in SAP and its variability components. The
      index alpha (a frequency domain measure of baroreflex gain) was minimal in the
      smoking period. Habitual cigarette smoking is associated with signs of
      sympathetic predominance in the autonomic control of the sinoatrial (SA) node.
      Nicotine patches produce only minor disturbances of autonomic regulation. This
      corroborates their safe use in smoking-cessation strategies.

PMID- 9593072
TI  - Activation of L-type calcium channel by tolazoline derivatives: role of
      isothiocyanate moiety.
AB  - Studies have investigated the pharmacologic mechanism of 2-(4'
      isothiocyanatobenzyl) imidazoline (IBI) and analogs for interaction with
      imidazoline receptors (IRs), alpha-adrenergic receptors (alpha-ARs), and calcium
      channels in cardiovascular muscle systems. IBI differs from tolazoline by
      substitution of an electrophilic isothiocyanato (NCS) group. Unlike tolazoline,
      which is a partial alpha-AR agonist, IBI produced an irreversible, slow-onset,
      and sustained contraction of rat aorta with an median effective concentration
      (EC50) value of 5 microM, and a maximal contraction (116%) greater than that of
      phenylephrine (100%) and tolazoline (59%). The IBI-induced contractions were
      dependent on calcium channels and independent of alpha-ARs or IRs. Similarly,
      structure-activity relation studies in rat aortic smooth muscles on a series of
      synthesized IBI analogs indicated that NCS analogs, but not those without the NCS
      group, exhibited effects by a non-alpha-AR, non-IR, but a calcium channel
      dependent mechanism. Thus the presence of an intact IBI ring in these analogs is
      not a requirement for these activities. Further, IBI inhibited dihydropyridine
      (DHP, [3H]PN 200-110 and [3H]Bay K 8644) binding to L-type calcium channels of T
      tubule membranes in rabbit skeletal muscle. In contrast to nifedipine, IBI and
      NCS derivatives (nifedipine-NCS, naphazoline-NCS) only partially (50-88%)
      displaced specific binding of these radioligands. A single site of noncooperative
      interaction was observed for nifedipine (nH = 0.97), whereas tolazoline-NCS (IBI,
      nH = 1.46) and nifedipine-NCS (nH = 1.37) exhibited a positive cooperativity in
      binding to DHP sites. These receptor-binding data indicate that NCS derivatives
      bind to L-type calcium channels and interact allosterically with DHP-binding
      sites. Direct binding of the NCS group to specific nucleophilic protein sites of
      the calcium channel may be responsible for its activation and the subsequent
      contractile effects of IBI.

PMID- 9593073
TI  - Angiotensin-converting enzyme inhibition produces electrophysiologic but not
      antiarrhythmic effects in the intact heart.
AB  - Although angiotensin-converting enzyme (ACE) inhibitors are known to influence
      favorably the structural remodeling of the heart after myocardial infarction, the
      mechanisms by which ACE inhibitors improve survival are not well understood. The
      hypothesis that ACE inhibitors may possess antiarrhythmic activity has been
      studied in various isolated tissue preparations. However, the electrophysiologic
      effects of ACE inhibitors in the intact heart are not well understood. The effect
      of the ACE inhibitor enalaprilat on intact heart electrophysiology was studied by
      using multisite optical action-potential recordings with voltage-sensitive dyes.
      Action potentials were recorded simultaneously from 128 left ventricular
      epicardial sites in 15 Langendorff perfused hearts subjected to an endocardial
      cryoablation procedure, which was used to restrict propagation to a thin viable
      rim of epicardium. Action-potential duration (APD) was significantly prolonged in
      67% of preparations perfused with 5 mg/L enalaprilat. Higher concentration of
      enalaprilat (50 mg/L) prolonged APD in all preparations tested. This APD
      prolonging effect persisted over a broad range of stimulus rates, indicating the
      absence of reverse use-dependent properties. Enalaprilat did not modify
      conduction velocity, nor did it affect spatial dispersion of repolarization
      times. In addition, enalaprilat had no effect on ventricular fibrillation
      threshold and failed to suppress the initiation of ventricular tachycardia using
      an anatomically defined reentrant circuit. These findings indicate that in the
      intact heart, enalaprilat does indeed have electrophysiologic effects that cause
      APD prolongation, particularly at high drug concentrations. However, this effect
      was not of sufficient magnitude in the guinea pig to suppress the initiation of
      ventricular fibrillation or reentrant ventricular tachycardia.

PMID- 9593075
TI  - A highly selective beta1-adrenergic blocker with partial beta2-agonist activity
      derived from ferulic acid, an active component of Ligusticum wallichii Franch.
AB  - Short-term injection of ferulinolol (0.1, 0.5, and 1.0 mg/kg, i.v.) produced dose
      dependent bradycardia responses in pentobarbital-anesthetized Wistar rats,
      whereas it had no significant effects on the blood pressure. Ferulinolol markedly
      inhibited the tachycardia effects induced by (-)isoproterenol but did not show
      any blocking effect on the arterial pressor responses induced by (
      )phenylephrine. These findings clearly suggested that ferulinolol had a beta
      adrenergic blocking activity; nevertheless, it did not involve an alpha
      adrenergic blocking action. In isolated guinea pig tissues, ferulinolol
      competitively antagonized (-)isoproterenol-induced positive inotropic and
      chronotropic effects of the atria and tracheal relaxation responses. The parallel
      shift to the right of the concentration-response curve of (-)isoproterenol
      suggested that ferulinolol was a beta-adrenoceptor-competitive antagonist. The
      apparent pA2 values for ferulinolol on right atria, left atria, and trachea were
      7.62 +/- 0.05, 7.54 +/- 0.01, and 6.28 +/- 0.11, respectively. Ferulinolol was
      more potent on the atria than on tracheal tissues, demonstrating that it
      possessed beta1-adrenoceptor selectivity. The intrinsic sympathomimetic activity
      (ISA) of ferulinolol and propranolol were determined on isolated atria and
      trachea from reserpine-treated guinea pig. Propranolol caused significantly
      negative inotropic and chronotropic effects at > or =1 microM, whereas
      ferulinolol possessed fewer cardiodepressant activities than propranolol. In
      reserpine-treated tracheal strips, ferulinolol produced dose-dependent relaxant
      responses, but propranolol was without effectiveness. Preincubating the
      preparations with ICI 118,551 (0.1, 1.0, and 10 nM), a beta2-adrenoceptor
      antagonist, significantly shifted the concentration-relaxation curves of
      ferulinolol to a region of higher concentrations. These results implied that
      ferulinolol had a partial beta2-agonist activity. Further, binding
      characteristics of ferulinolol and various beta-adrenoceptor antagonists were
      evaluated in [3H]CGP-12177 binding to rat ventricular or lung membranes. The Ki
      values of ferulinolol, atenolol, metoprolol, and (-)propranolol were 103, 262,
      123, and 0.23 nM, respectively, in ventricular membranes, and 2,412, 7,539,
      2,186, and 0.72 nM, respectively, in lung membranes. In conclusion, ferulinolol
      was found to be a highly selective beta1-adrenoceptor antagonist with partial
      beta2-agonist activity but was devoid of alpha-adrenoceptor blocking action.

PMID- 9593074
TI  - Coronary vasorelaxant effect of levosimendan, a new inodilator with calcium
      sensitizing properties.
AB  - We examined the action of levosimendan, a new Ca2+-sensitizing inodilator, on
      isolated porcine coronary arteries. Vessel rings were studied in isometric
      myographs. Arterial cyclic adenosine monophosphate (cAMP) levels were determined
      by radioimmunoassay. Levosimendan (10(-7)-10(-3) M) completely relaxed arteries
      preconstricted by prostaglandin F2alpha (PGF2alpha) with a pD2 (-logEC50) value
      of 3.99 +/- 0.05 (n = 6-9 in all experiments). Pretreatment with levosimendan
      also prevented contraction induced by PGF2alpha. The vasorelaxation produced by
      levosimendan (10(-7)-10(-3) M) was not attenuated by removal of the endothelium.
      Levosimendan (10(-7)-10(-3) M) relaxed contractions induced by 30 mM K+ as well
      as 80 mM K+, whereas the K+ channel opener levcromakalim selectively relaxed
      contraction induced by 30 mM K+. Neither the cyclooxygenase inhibitor
      indomethacin nor the beta-adrenoceptor blocker propranolol influenced
      levosimendan-induced vasorelaxation. The Ca2+-entry blocker isradipine failed to
      relax arteries precontracted by endothelin-1 in Ca2+-free/EGTA medium. However,
      levosimendan (10(-7)-3 x 10(-3) M) completely relaxed endothelin-1-induced
      contractions in this medium. Levosimendan potentiated the relaxant effect of a
      cAMP-stimulating drug, isoprenaline, but also that of nitroglycerin and
      isradipine. At a maximal effective concentration, it increased arterial tissue
      contents of cAMP twofold. In conclusion, levosimendan produces coronary
      vasorelaxation by a mechanism that seems to be endothelium independent and not
      mediated by K+ channel opening, Ca2+-entry blockade, release of cyclooxygenase
      products, or beta-adrenoceptor stimulation. Accumulation of cAMP may possibly
      participate in vasorelaxation at high concentrations of levosimendan, but a cAMP
      independent mechanism seems to be involved at lower concentrations.

PMID- 9593076
TI  - Effects of platelet-activating factor on intracellular Ca2+ concentration and
      contractility in isolated cardiomyocytes.
AB  - We investigated the effects of platelet-activating factor (PAF, 1-O-alkyl-2
      acetyl-sn-glycero-3-phosphocholine) on intracellular Ca2+ concentration ([Ca2+]i)
      and cell length in isolated and field-stimulated rat cardiomyocytes. [Ca2+]i and
      cell length of field-stimulated cells were determined simultaneously by confocal
      laser scan microscopy by using the fluorescent Ca2+ dye Fluo-3. PAF (10(-12)-10(
      8) M) inhibited systolic [Ca2+]i increase in a time- and concentration-dependent
      manner. Maximal effects were observed after an incubation time of 6-8 min,
      resulting in a 17% (10(-12) M), 41% (10(-10) M), and 52% (10(-8) M PAF)
      inhibition of systolic [Ca2+]i increase. A time- and concentration-dependent
      decrease in simultaneously measured cell shortening also was demonstrated. Cell
      shortening was inhibited by 10% (10(-12) M), 32% (10(-10) M), and 50% (10(-8) M)
      after an incubation time of 8 min. The effects of PAF could be antagonized by the
      PAF-receptor antagonist WEB 2170. These data demonstrate that PAF receptor
      dependently induces a negative inotropic effect, which is correlated with a
      decrease in systolic [Ca2+]i and is most likely not due to a decrease in
      myofilament sensitivity.

PMID- 9593077
TI  - Streptokinase-induced activation of the kallikrein-kinin system and of the
      contact phase in patients with acute myocardial infarction.
AB  - Thrombolytic therapy in acute myocardial infarction (AMI) is hampered by a
      considerable reocclusion rate. Thrombin activity is enhanced, and contact-system
      activation via plasminemia might be possible. Prospectively we examined the
      contact phase and the kallikrein-kinin system and additional molecular markers of
      hemostasis and fibrinolysis in AMI. In 22 patients with AMI, blood sampling was
      performed at admission and < or =10 days afterward. Eleven patients received 1.5
      Mio U streptokinase (group A) and were compared with 11 AMI patients without
      thrombolytic therapy (group B). All patients had systemic heparinization (5,000
      IU bolus, i.v.; 1,000 IU/h, i.v.). In group A (vs. group B), the kallikrein
      factor XII system was significantly activated (3 h after start of therapy):
      kallikrein activity 140 +/- 41 (vs. 43 +/- 8) U/L (p < 0.05); kallikrein
      inhibition 87 +/- 9 (vs. 113 +/- 7%; p < 0.05), and factor XII 70 +/- 14 (vs. 94
      +/- 6%). C1 inhibitor and factor XII inhibition were decreased. High-molecular
      weight kininogen consumption indicating bradykinin generation was enhanced (p <
      0.01). In group A, thrombin activity (TAT) was increased, and a hypercoagulative
      state with increased fibrin degradation products (d-dimer) was found. Plasmin
      activation in group A was reflected by decreased plasminogen and antiplasmin
      levels (p < 0.01). The findings indicate that streptokinase induces activation of
      the contact phase-kinin system in vivo associated with a consecutive increase of
      thrombin and bradykinin generation. Activation of this pathway might
      substantially contribute to reocclusion after initially successful thrombolytic
      therapy and to hypotensive reactions observed after streptokinase.

PMID- 9593078
TI  - Direct effects of statins on the vascular wall.
AB  - The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors (statins) on coronary events have generally been attributed
      to their hypocholesterolemic properties. Mevalonate and other intermediates of
      cholesterol synthesis (isoprenoids) are necessary for cell proliferation and
      other important cell functions; thus effects other than cholesterol reduction may
      help to explain the antiatherosclerotic properties of statins. Recently we
      provided in vitro and in vivo evidence of decreased smooth-muscle cell (SMC)
      proliferation and migration by fluvastatin and simvastatin, but not by
      pravastatin, independent of plasma cholesterol reduction. The ability of
      fluvastatin to interfere with arterial SMC proliferation at therapeutic
      concentrations (0.1-1 microM) prompted us to investigate the pharmacologic
      activity of sera from 10 patients treated with fluvastatin, 40 mg once daily, on
      the proliferation of cultured human arterial myocytes. Pravastatin, 40 mg once
      daily, displays a lipid-lowering activity similar to that of fluvastatin without
      affecting SMC proliferation and was investigated as a control for assessing this
      non-lipid-related effect of fluvastatin. Fluvastatin and pravastatin, given for 6
      days to patients with type IIa hypercholesterolemia, resulted in a similar
      decrease in low-density-lipoprotein (LDL) cholesterol. However, the addition of
      15% whole-blood sera from patients treated with fluvastatin to the culture medium
      resulted in a 43% inhibition of cholesterol synthesis in SMCs (p < 0.01) that
      mirrored the pharmacokinetic profile of fluvastatin. When SMC proliferation was
      investigated, a significant inhibition of cell growth (-30%; p < 0.01) was
      detected with sera obtained 6 h after the last dose. No effect on SMC
      proliferation or cholesterol biosynthesis was observed when sera from patients
      treated with pravastatin were evaluated. These results suggest that statins exert
      a direct antiproliferative effect on the arterial wall, beyond their effects on
      plasma lipids, which could prevent significant cardiovascular disease.

PMID- 9593079
TI  - Cardiac mast cell stabilization and cardioprotective effect of ischemic
      preconditioning in isolated rat heart.
AB  - This study was designed to investigate the effect of disodium cromoglycate
      (DSCG), a mast cell stabilizer, on cardioprotective effect of ischemic
      preconditioning. Isolated rat heart was subjected to 30 min of global ischemia
      followed by 30 min of reperfusion. Ischemic preconditioning was provided by four
      episodes of 5-min global ischemia followed by 5 min of reperfusion before
      sustained ischemia. Ischemic preconditioning and DSCG (10 and 100 microM)
      treatment markedly decreased the release of lactate dehydrogenase (LDH) and
      creatine kinase (CK) in coronary effluent and percentage incidence of ventricular
      premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during
      reperfusion. Ischemic preconditioning and DSCG treatment also significantly
      reduced ischemia/reperfusion-induced mast cell peroxidase (MPO) release, a marker
      of mast cell degranulation. A significant increase in MPO release was observed
      immediately after ischemic preconditioning, and the release was found to be
      inhibited in hearts perfused with DSCG (10 and 100 microM) during ischemic
      preconditioning. DSCG administered during ischemic preconditioning (DSCG in
      ischemic preconditioning) attenuated the cardioprotective and antiarrhythmic
      effects of ischemic preconditioning. DSCG in ischemic preconditioning produced no
      marked effect on ischemia/reperfusion-induced MPO release. These findings
      tentatively suggest that DSCG administration during ischemic preconditioning
      abolishes its cardioprotective effect, perhaps by stabilizing resident cardiac
      mast cells.

PMID- 9593080
TI  - Amlodipine inhibition of serum-, thrombin-, or fibroblast growth factor-induced
      vascular smooth-muscle cell proliferation.
AB  - Atherosclerosis, like several other vascular diseases, exhibits structural and
      functional abnormalities resulting partially from an exaggerated proliferation of
      vascular smooth-muscle cells (VSMCs). Ca2+ channel blockers, such as amlodipine,
      have been suggested to retard or even prevent the progression of atherosclerosis.
      To determine the mechanisms involved in these effects, we investigated the
      influence of amlodipine on VSMC proliferation by using rat aortic VSMCs in
      culture. Amlodipine (0.1-10 microM) inhibited serum-, basic fibroblast growth
      factor (bFGF)-, and thrombin-induced VSMC proliferation and DNA synthesis in a
      concentration-dependent manner, as demonstrated by cell count and
      bromodeoxyuridine (BrdU)-incorporation measurements, respectively. Delayed
      addition of amlodipine after VSMC stimulation showed that the drug exerted its
      effect early in G1 phase of the cell cycle. This observation was confirmed by the
      finding that amlodipine did not influence DNA synthesis in VSMCs arrested to the
      G1/S boundary by hydroxyurea treatment. Consistent with its effects on VSMC
      growth/proliferation, amlodipine also decreased c-myc, c-fos, and c-jun
      protooncogene expression induced by serum, thrombin, or bFGF within 1 h after
      cell activation, as assessed by semiquantitative reverse transcriptase (RT)
      polymerase chain reaction (PCR) analysis. The calcium channel agonist Bay K 8644,
      which counteracted the inhibition by nifedipine of bFGF-, thrombin- or serum
      induced DNA synthesis, was ineffective to antagonize the inhibitory effect of
      amlodipine. The aforementioned effects of amlodipine were of similar amplitude,
      irrespective of the growth-enhancing agent used. This strongly indicates that
      amlodipine acts downstream of receptor activation to exert its antiproliferative
      action, probably early in the G1 phase of the cell cycle. Moreover, the lack of
      antagonistic effect between amlodipine and Bay K 8644 suggests that, in addition
      to its L-type Ca2+ channel inhibitory effect, amlodipine inhibits other
      intracellular signaling pathways. Such an interference of amlodipine with
      mitogenic signaling pathways might contribute to confer a blood vessel-protecting
      potential on amlodipine.

PMID- 9593081
TI  - P2X purinoceptors in postmortem human cerebral arteries.
AB  - Pharmacological studies have demonstrated that various purinoceptors are involved
      in the control of the cerebral vascular tone in many species. In this study, the
      existence of P2X purinoceptors in the postmortem human cerebral arteries was
      investigated with organ-bath pharmacology, autoradiography, and
      immunohistochemistry. Specimens were obtained from the M2 region of the middle
      cerebral arteries from human cadavers with an age range of 53-91 years and
      postmortem time of 37-54 h. Application of alpha,beta-methylene adenosine
      triphosphate (ATP) produced concentration-dependent contraction in the arterial
      ring, whereas transmural nerve stimulation and noradrenaline did not elicit
      contraction. Autoradiography using [3H]alpha,beta-methylene ATP (a radioligand
      for P2X purinoceptors) showed specific [3H]alpha,beta-methylene ATP binding sites
      in the smooth-muscle cells of the postmortem human cerebral arteries.
      Immunohistochemistry with specific P2X1 purinoceptor antibodies revealed positive
      staining exclusively in the smooth muscle of the same specimens. All these
      results demonstrate the existence of P2X purinoceptors in human cerebral
      arteries, which were still functionally active despite the long postmortem time.
      The results from this study suggest that the postmortem human cerebral arteries
      can be useful specimens for studying the P2X purinoceptor-mediated responses.

PMID- 9593082
TI  - Late sodium current inhibition in human isolated cardiomyocytes by R 56865.
AB  - R 56865, a cytoprotective agent, has been shown to prevent myocardial ischemia
      and reperfusion injury by blockade of the late sodium current (I(Nal)). The
      effect of R 56865 on I(Nal) in isolated human atrial myocytes was investigated by
      using the whole-cell patch-clamp technique. I(Nal) recorded at the end of a 350
      ms test pulse evoked from -100 to +20 mV was significantly increased by the
      addition of veratrine (100 microg/ml: quantity of charge corresponding to total
      I(Nal): 6.1 +/- 1.2 at baseline vs. 86.9 +/- 15; p < 0.001). Tetrodotoxin (TTX; 1
      microM) fully prevented veratrine-induced increases in I(Nal). R 56865 (0.1-10
      microM, n = 14) significantly and reversibly decreased veratrine-induced I(Nal)
      (42.01 +/- 8.6%, n = 6; p < 0.001 at 10 microM). Moreover, R 56865 reduced I(Nal)
      without significantly affecting kinetic parameters of inactivation [tau1 = 1.04
      +/- 0.1 ms and tau2 = 119.3 +/- 2.3 ms (baseline) vs. tau1 = 1.57 +/- 0.5 ms and
      tau2 = 134.4 +/- 14 ms in the presence of 10 microM R 56865; NS]. The data
      indicate that R 56865 is a potent blocker of the late inducible component of
      sodium current in human cardiomyocytes.

PMID- 9593083
TI  - Outcome after hemiarthroplasty for three- and four-part fractures of the proximal
      humerus.
AB  - We reviewed 27 patients who had sustained displaced three- or four-part fractures
      of the proximal humerus and who were treated with a humeral hemiarthroplasty.
      Seventeen patients had a three-part fracture, and 10 had a four-part fracture.
      The mean follow-up period was 39 months (12 to 94 months). All fractures were
      classified according to Neer's classification. The Constant score was used for
      their follow-up evaluation. The median Constant score at follow-up was 51 for the
      three-part fractures and 46 for the four-part fractures. The median range of
      movement for all the patients in flexion was 70 degrees, abduction 70 degrees,
      internal rotation 50 degrees, and external rotation 45 degrees. Nine patients
      still had moderate or severe pain. Eight patients had moderate or severe
      disability. Our results were disappointing, and further studies on open reduction
      and fixation are therefore justified.

PMID- 9593085
TI  - The deltoid extension lag sign for diagnosis and grading of axillary nerve palsy.
AB  - The deltoid extension lag sign has been developed to avoid the pitfalls
      confounding the diagnosis of an axillary nerve lesion. The physician elevates the
      arm into a position of near full extension. The patient is asked to attempt
      active maintenance of this position. If the deltoid is weak, the arm will drop.
      In five patients with traumatic axillary nerve palsy after anterior dislocation
      of the shoulder, the deltoid extension lag sign was used to evaluate the
      functional status of the deltoid muscle. The magnitude of the angular drop, or
      lag, of the arm was a precise indicator of the functional status and recovery of
      the deltoid. The sign proved to be objective and reproducible, allowing confident
      assessment of deltoid function and when repeated over time allowed precise follow
      up of deltoid recovery.

PMID- 9593084
TI  - Functional outcome after the L'Episcopo procedure.
AB  - A study was undertaken to assess functional outcome in 11 patients undergoing
      latissimus dorsi and teres major transfer (L'Episcopo procedure) for external
      rotation deficient shoulders. The mean age was 37 years (range 18 to 48 years).
      All of the patients had adult-onset brachial plexus injuries. The mean time for
      injury to operation was 32 months. Patients were evaluated by questionnaire,
      measurement of the range of motion, strength testing, and an overhead work
      simulation. Of the patients studied, 10 of the 11 patients were working (8
      returned to their preinjury employment). The cumulative postoperative mean
      activities of daily living score was 20 (maximum possible 33) compared with 14
      before surgery. No complications occurred. Ten patients reported confidence in
      the limb and believed the procedure was worthwhile. Mean active external rotation
      of the shoulder at 0 degrees and 90 degrees elevation was 28 degrees (range 15
      degrees to 55 degrees and 36 degrees (range 0 degrees to 90 degrees),
      respectively. Postoperative external rotation strength was 0.32 that of the
      control side with the arm at the side. Seven of the nine patients tested were
      able to complete the Valpor overhead work simulation. The L'Episcopo muscle
      tendon transfer reliably improves functional outcome in the late functional
      reconstruction of adult-onset brachial plexus lesions.

PMID- 9593086
TI  - Subluxations and dislocations of the tendon of the long head of the biceps.
AB  - Seventy-one cases of subluxation or dislocation of the long head of the biceps
      tendon (LHB) were retrospectively evaluated. Subluxation was observed in 25 (35%)
      cases combined with partial tearing of the subscapularis tendon and in 70% with
      tears of the supraspinatus tendon. Dislocation was defined as a permanent loss of
      contact between the tendon and the intertubercular groove; it was observed in 46
      (65%) cases. Dislocation was associated with complete rupture of the
      subscapularis tendon in 23 cases, with partial tearing in 21 cases, and with an
      intact subscapularis tendon in 2 cases. Out of a series of 445 rotator cuff
      repairs, medial displacement of the LHB was found in 16%. In 70% of all cases
      dislocation of the long biceps tendon was associated with massive rotator cuff
      tears including the supraspinatus and infraspinatus tendons. Although
      "pseudoparalysis" of the shoulder (sudden loss of active elevation) was observed
      in 46% of all cases, no specific clinical test correlated to the presence of
      medial displacement of the LHB. Arthrography revealed displacement of the LHB in
      28%, whereas arthro-computed tomography demonstrated lesions in 76%. The authors
      believe that medial displacement of the LHB can easily be overlooked during open
      surgery, and opening of the rotator interval is an essential part of rotator cuff
      repair.

PMID- 9593087
TI  - Anatomic variation of the mechanical properties of the glenoid.
AB  - Finite element analysis modeling is an important tool in the design of total
      joint replacements. However, to use a finite element analysis the material
      properties of the studied bone must be known. The aim of the study was to measure
      the elastic properties of the glenoid bone in the axial, coronal, and sagittal
      planes with an ultrasound transmission technique. The relative density and
      Houndsfield computed tomography numbers were also assessed. Three pairs of
      scapulas were obtained from unembalmed human cadavers. Seventy-four cubic
      cancellous bone specimens of 6 mm were used for ultrasonic measurements. The
      study showed significant differences with anatomic location. Mechanical
      properties of cancellous bone were found to be higher near the direction of
      application of the resultant force, perpendicular to the articular surface of the
      glenoid. Mechanical properties were found to be significantly higher at the
      center and posterior edge of the glenoid (p < 0.01). Significant differences were
      also found in the three planes studied. The lateromedial Young's modulus (E1) was
      higher than the anteroposterior modulus (E2) and the superoinferior modulus (E3)
      (E1 = 372 +/- 164 MPa, E2 = 222 +/- 79 MPa, E3 = 198 +/- 75 MPa).

PMID- 9593088
TI  - A standard method of shoulder strength measurement for the Constant score with a
      spring balance.
AB  - The strength component of the Constant score has been criticized for its lack of
      a precisely defined measurement method. A series of experiments was performed to
      compare three different methods in normal and pathologic shoulders with the use
      of a standard test position. These were (1) the Isobex isometric dynamometer, (2)
      Constant's unsecured spring balance, and (3) a new modification in which the
      spring balance is fixed at one end and the reading is taken after 5 seconds of
      maximum effort. The results suggest that this simple modification with a low-cost
      spring balance can give similar values to those from the Isobex. The need for
      precision of terms and a definition of the method is discussed, and
      recommendations for the standardization of the many variables in making this
      measurement are made.

PMID- 9593089
TI  - The anatomy of the glenohumeral ligamentous complex and its contribution to
      anterior shoulder stability.
AB  - One hundred four enbalmed cadaver shoulders were evaluated. With a dorsal
      approach we opened the dorsal capsule after resecting the infraspinatus and teres
      minor muscles. For reaching the anterior capsule and the glenohumeral ligaments,
      the humeral head was resected. In this way we could quantify and qualify the
      glenohumeral ligaments and classify the synovial recesses based on the
      classification system of DePalma into type I to VI. Secondary signs of shoulder
      instability were documented. The superior glenohumeral ligament was missing in 6
      (5.8%) shoulders, the middle glenohumeral ligament in 16 (15.4%) shoulders, and
      the inferior glenohumeral ligament in 7 (6.8%) shoulders. Most of the synovial
      recesses belonged to group I (38.5%) and III (46.2%). As a secondary sign of
      instability four shoulders had a Hill-Sachs fracture and a bony Bankart lesion.
      All four shoulders had no middle glenohumeral ligament and a large anterior type
      IV recess.

PMID- 9593090
TI  - The effect of comorbidity and duration of nonunion on outcome after surgical
      treatment for nonunion of the humerus.
AB  - The purpose of our study was to assess the effect of comorbidity and duration of
      nonunion on the general health status and joint-specific outcome of a group of
      patients treated for nonunion of the humeral shaft. We identified 25 consecutive
      patients with nonunion of the humeral shaft, all treated with compression plating
      and bone grafting. Twenty-one patients returned for a comprehensive assessment
      including completion of the SF 36 Health Status Survey and determination of the
      Constant shoulder and Morrey elbow scores. Thirteen patients had > or = 1
      comorbid conditions. Eleven patients had a nonunion of > 8 months' duration, and
      10 had a nonunion of < 8 months' duration. Follow-up at a mean of 42 months
      (range 12 to 99 months) revealed that all nonunions united an average of 5 months
      after surgery. The mean Morrey elbow score was 94, Constant shoulder score 82,
      and "global" SF 36 score 59.4. The physical portion of the SF 36 score correlated
      well with the Constant and Morrey scores (p = 0.047 and p = 0.027, respectively).
      The presence of comorbid factors had a significant negative effect on the SF 36
      scores (p = 0.001) but no effect on joint-specific Morrey or Constant scores. The
      duration of nonunion had no effect on SF 36 or joint-specific scores. Although
      the reliability of the SF 36 is illustrated by the close correlation between its
      "physical function" portion and standard (joint-specific) outcome measures,
      comorbidity has a significant negative effect on overall scores. This must be
      considered when such tools are used for assessment of orthopaedic intervention.

PMID- 9593091
TI  - Critical analysis of the supraspinatus outlet view: rationale for a standard
      scapular Y-view.
AB  - The supraspinatus outlet view has been standardized under fluoroscopic control to
      become reproducible and comparable; it is the normalized scapular Y-view. Four
      hundred four healthy shoulders from patients 20 to 80 years old and 63 shoulders
      with rotator cuff tears underwent x-ray evaluation and were compared. A
      qualitative study was carried out on the shape of the acromion in relation to
      Bigliani's types (I, II, III and on the presence or absence of a bony spur on the
      anterior part of the acromion. Quantitative measurements were determined; the
      subacromial peak and the spinoacromial angle were assessed for a statistical
      comparison among the various populations. The acromions of healthy shoulders
      varied with age (8% type III in patients younger than 60 years, 27% in those
      older than 60 years), although not significantly. The dominant side and sex of
      the subjects had no effect. With 29% type III acromions the shoulders with cuff
      tears differed from those of the healthy shoulders (14% type III). No close
      correlation was seen between type III acromions and cuff ruptures. The
      quantitative values of the acromions had no predictive value for cuff rupture.
      Acromion typology failed to confirm that a type III acromion was responsible for
      rotator cuff rupture. Spurs are found in increasing incidence with age and in the
      presence of cuff rupture; whether they are caused by subacromial impingement or
      by natural aging of the acromion is uncertain.

PMID- 9593093
TI  - The use of the bicipital groove for alignment of the humeral stem in shoulder
      arthroplasty.
AB  - Four hundred twenty humeri were measured to determine humeral head retroversion
      and its relation to the location of the bicipital groove. Average head
      retroversion was found to be 28.3 degrees (+/- 13.2 degrees), and the angular
      orientation of the bicipital groove referenced to the transepicondylar axis was
      55.5 degrees (+/- 13.8 degrees). The average difference between these angular
      orientations was 27.3 degrees (+/- 14.2 degrees). This result implies that the
      bicipital groove can be used as a landmark for prosthetic stem positioning in
      shoulder arthroplasty if the center of the lateral aspect of the stem is
      posteriorly offset approximately 30 degrees from the center of the groove.
      However, because of the appreciable variation in these averages, the use of the
      bicipital groove as a reference can result in a significant error of humeral stem
      alignment, which should be considered when determining the retroversion for a
      particular patient.

PMID- 9593092
TI  - The effects of arthroscopic acromioplasty on the acromioclavicular joint.
AB  - Thirty patients with 31 shoulders underwent clinical and radiologic evaluation 5
      to 6 years after arthroscopic acromioplasty. The mean age was 51 years. The
      acromioclavicular (AC) joint was assessed for tenderness on palpation and pain on
      horizontal adduction of the shoulder. All patients underwent a radiologic
      examination consisting of an anteroposterior view of the AC joint and bilateral
      stress views. No patient had superior translation or widening of more than 1 mm
      of the AC joint on stress views on the unoperated side. On the operated side 12
      (38%) shoulders showed signs of instability consisting of a superior translation
      of the clavicle of 2 to 3 mm, distraction on weight bearing view, or both. No
      severely osteoarthritic AC joint (grade 3 or 4) was unstable. The degree of
      osteoarthritis did not differ for both shoulders, suggesting that arthroscopic
      acromioplasty does not accelerate osteoarthritic change in the AC joint but can
      induce instability. Nine patients had tenderness over the AC joint and
      instability on stress views. They had a significantly reduced University of
      California Los Angeles score of 25 +/- 5 compared with the other patients (29.5
      +/- 7). We conclude that preservation of the inferior capsule during arthroscopic
      acromioplasty is important for the integrity of the AC joint in patients without
      severe osteoarthritic changes.

PMID- 9593094
TI  - Diagnostic injection around the shoulder: hit and miss? A cadaveric study of
      injection accuracy.
AB  - In a cadaver study the success of injections in the subacromial space and
      acromioclavicular joint was studied. Twenty-four shoulders were dissected after
      separate dye injection was performed with the patient in the supine position.
      Subacromial bursa injection was successful in 83% (20 shoulders), but in 15
      shoulders other structures were also infiltrated, including seven injections in
      the rotator cuff. Acromioclavicular joint injection was successful in 67% (16
      shoulders), but half involved other structures. The authors believe that
      misplaced injections may be diagnostically misleading and potentially harmful.

PMID- 9593095
TI  - Triceps tendon rupture in weight lifters.
AB  - Triceps tendon avulsion injuries are rare. We report four weight lifters with
      triceps tendon raptures, two of whom had received local steroid injections for
      pain in the triceps. All four patients had taken oral anabolic steroids before
      injury. All patients had closed avulsion of the triceps tendon from its insertion
      into the olecranon. Three patients were injured while bench pressing heavy
      weights, and one patient was injured while swinging a baseball bat. Satisfactory
      results were achieved after surgical reinsertion of the tendon.

PMID- 9593096
TI  - Hematogenous abscess of the subacromial/subdeltoid bursa in a child.

PMID- 9593097
TI  - Posterior capitellum impression fracture: a case report associated with
      posterolateral rotatory instability of the elbow.

PMID- 9593098
TI  - Osteoid osteoma of the elbow.

PMID- 9593099
TI  - Stress fracture of the clavicle in a professional baseball player.

PMID- 9593100
TI  - Altropane, a SPECT or PET imaging probe for dopamine neurons: I. Dopamine
      transporter binding in primate brain.
AB  - Increasing evidence suggests that the dopamine transporter is an important marker
      for physiological and pathological changes in dopamine neurons. Potent dopamine
      transport inhibitors of the phenyltropane series (e.g., WIN 35,428 or CFT) are
      particularly suitable for PET (positron emission tomography) or SPECT (single
      photon emission computed tomography) imaging of the dopamine transporter in
      living brain. We investigated whether altropane, an N-iodoallyl analog of WIN
      35,428 (IACFT:E-N-iodoallyl-2 -carbomethoxy-3beta-(4-fluorophenyl)tropane),
      displayed in vitro properties suitable for evaluation as a SPECT imaging agent.
      In brain striatum of cynomolgus monkey (Macaca fascicularis), the unlabeled E
      isomer (IC50: 6.62 +/- 0.78 nM) was more potent than the Z-isomer (IC50: 52.6 +/-
      0.3 nM) and displayed a relatively high dopamine:serotonin transporter
      selectivity (28-fold). In radiolabeled form, [125I]altropane bound to sites in
      the striatum with a single high affinity (KD: 5.33 +/- 0.55 nM) and with a site
      density (BMAX: 301 pmol/g original wet tissue weight) that was within the density
      range reported previously for the dopamine transporter in striatum. Drugs
      inhibited [125I]altropane binding with a rank order of potency that corresponded
      closely to their potencies for inhibiting [3H]WIN 35,428 binding (r2: 0.99; P <
      0.0001) to the blocking dopamine transport. The favorable binding properties of
      altropane, together with its rapid entry into primate brain and highly localized
      distribution in dopamine-rich brain regions, suggest it is a suitable iodinated
      probe for monitoring the dopamine transporter in vitro and in vivo by SPECT or
      PET imaging.

PMID- 9593101
TI  - Altropane, a SPECT or PET imaging probe for dopamine neurons: II. Distribution to
      dopamine-rich regions of primate brain.
AB  - The dopamine transporter in brain, localized almost exclusively on dopamine
      neurons, is an effective window on dopamine neurons. SPECT or PET imaging of the
      transporter in brain requires selective imaging agents that display appropriate
      pharmacokinetic properties. We previously reported that [125I]altropane
      ([125I]IACFT,2beta-carbomethoxy-3beta-(4-fluorophenyl)-n-(1- iodoprop-1-en-3
      yl)nortropane) bound with high affinity (Kd: 5.33 nM) to a single site on the
      dopamine transporter and was selective for dopamine over the serotonin
      transporter in homogenates of monkey striatum. To determine whether the selective
      binding of [125I]altropane is reflected in its brain distribution, the in vitro
      and ex vivo distribution of [125I]altropane in squirrel monkey (Saimiri sciureus)
      brain was determined by quantitative autoradiography of coronal brain sections.
      In vitro, [125I]altropane (2 nM) distribution was discrete and was detectable
      primarily in the dopamine-rich putamen, caudate nucleus, and nucleus accumbens.
      The resulting putamen:cerebellum ratio exceeded 120:1 (n = 3). The selective in
      vitro binding of [125I]altropane to the dopamine transporter, at concentrations
      approaching its Kd value (Kd: 5.33 nM, a single high affinity site), highlight
      its suitability for investigating the density of the dopamine transporter in
      various brain regions in vitro. Ex vivo autoradiography was conducted in monkeys
      to determine whether the brain distribution of [125I]altropane in vitro was
      predictive of its brain distribution pattern after intravenous administration.
      Thirty minutes after intravenous injection, highest levels of [125I]altropane
      (0.3 nmol/kg) were detected in the caudate-putamen and nucleus accumbens and
      lowest levels in the cerebellum and cortex. The putamen or caudate:cerebellum
      ratio was 7. SPECT imaging of the brain within 30 min of i.v. injection confirmed
      the rapid and selective accumulation of [123I]altropane to the striatum. The
      selective binding of altropane to the dopamine-rich striatum within 30 min of
      i.v. administration indicates that it is uniquely suited for SPECT or PET imaging
      of the dopamine transporter and associated dopamine neurons.

PMID- 9593102
TI  - Altropane, a SPECT or PET imaging probe for dopamine neurons: III. Human dopamine
      transporter in postmortem normal and Parkinson's diseased brain.
AB  - Increasing evidence suggests that the dopamine transporter is situated almost
      exclusively on dopamine neurons. Accordingly, it is an valuable marker for
      Parkinson's disease and other pathological states of dopamine neurons. We
      previously demonstrated that the potent dopamine transport inhibitor
      [125I]altropane (IACFT:E-N-iodoallyl-2beta-carbomethoxy-3beta-(4-fluor
      ophenyl)tropane) is a high affinity selective probe for the dopamine transporter
      in monkey brain and an effective SPECT imaging agent in nonhuman primate brain.
      We now report the binding properties of [125I]altropane in postmortem tissue of
      normal human brain and compare the findings to Parkinson's diseased brain. In
      homogenates of human brain putamen, [125I]altropane bound with high affinity (KD:
      4.96 +/- 0.38 nM, n = 4) and site density (BMAX: 212 +/- 41.1 pmol/g original wet
      tissue weight) well within the density range reported previously for the dopamine
      transporter in this brain region. Drugs inhibited [125I]altropane binding with a
      rank order of potency that corresponded closely to their rank order for blocking
      dopamine transport (r 0.98, P < 0.001). In postmortem Parkinson's diseased brain,
      bound [125I]altropane (1 nM) was markedly reduced (89%, 99% in putamen, depending
      on measures of nonspecific binding) compared with normal aged-matched controls
      (normal putamen: 49.2 +/- 8.1 pmol/g; Parkinson's diseased putamen: 0.48 +/- 0.33
      pmol/g; n = 4). In vitro autoradiography, conducted in tissue sections at a
      single plane of the basal ganglia, revealed high levels of [125I]altropane
      binding the caudate nucleus and putamen, but lower levels (73% of the caudate
      putamen) in the nucleus accumbens (n = 7). In Parkinson's diseased brains (n =
      4), [125I]altropane binding was 13% of the levels detected in normal putamen, 17%
      of normal values in the caudate nucleus, and 25% of normal levels in nucleus
      accumbens. The association of [125I]altropane to the dopamine transporter in
      human postmortem tissue, the marked reduction of [125I]altropane binding in
      Parkinson's diseased brains, its rapid entry into brain and highly localized
      distribution in dopamine-rich brain regions, support its use as a probe for
      monitoring the dopamine transporter in vitro and in vivo by SPECT imaging.

PMID- 9593103
TI  - Rapid detection of Parkinson's disease by SPECT with altropane: a selective
      ligand for dopamine transporters.
AB  - Increasing evidence indicates that dopamine (DA) transporter density declines in
      Parkinson's disease (PD). 2Beta-carbomethoxy-3beta-(4-fluorophenyl)-n-(1-iodoprop
      1-en -3-yl) nortropane (IACFT, Altropane) is a cocaine analog with high affinity
      and selectivity for dopamine transporter (DAT) sites in the striatum. In this
      study, single photon emission computed tomography (SPECT) with [123I]altropane
      was used to measure DAT density in seven healthy volunteers (five males, age 37
      75, and two females, ages 26 and 39) and eight male patients with Parkinson's
      disease (age 14-79, Hoehn and Yahr stage: 1.5-3 (n = 5) and 4-5 (n = 3)). Dynamic
      SPECT images and arterial blood samples were acquired over 1.5-2 hr and plasma
      radioactivity was analyzed chromatographically to obtain metabolite corrected
      arterial input functions. Binding potential (BP, B'max/KD) for striatal (Str) DAT
      sites was calculated by two methods using occipital cortex (Occ) as a reference.
      In the first method, tissue time-activity curves (TAC) and metabolite corrected
      arterial input functions were analyzed by a linear graphical method developed for
      reversible receptor ligands. In the second method, the expression (Str(TAC) -
      Occ(TAC)) was fitted to a gamma variate function and the maximum divided by
      Occ(TAC) at the same time was used to estimate BP. In five of the PD patients,
      the SPECT data were compared with the results of PET with [18F] 6-fluoro DOPA (FD
      PET). Plasma analysis indicated that [123I]altropane is rapidly converted to
      polar metabolites. SPECT images in healthy volunteers showed that [123I]
      altropane accumulated rapidly and selectively in the striatum and yielded
      excellent quality images within 1 h after injection. Both methods of analysis
      revealed a 7.6%/decade reduction in BP and average striatal values (corrected to
      age 25) were 1.83 +/- 0.22 and 2.09 +/- 0.20 by methods 1 and 2. In all the PD
      patients, striatal accumulation was markedly reduced and the pattern of loss was
      similar to that reported for DA; most profound in the posterior putamen with
      relative sparing of the caudate nuclei. A comparable pattern was observed with FD
      PET. For total striatum, age-corrected BP was significantly (P < 0.001) reduced;
      0.83 +/- 0.06 (method 1), 0.84 +/- 0.07 (method 2). BPs measured by the two
      methods were remarkably similar and highly correlated r2 = 0.88, (P < 0.001).
      These results indicate that [123I]altropane is an excellent SPECT ligand for
      imaging the DAT/DA neurons in human brain. The high selectivity and rapid
      striatal accumulation of the ligand allows for accurate quantitation of DAT sites
      in less than 2 hr. The results further demonstrate that [123I]altropane is an
      effective marker for PD.

PMID- 9593104
TI  - Effects of NMDA antagonism on striatal dopamine release in healthy subjects:
      application of a novel PET approach.
AB  - Agents that antagonize the glutamatergic N-methyl-d-aspartate (NMDA) receptor,
      such as phenylcyclidine (PCP) and ketamine, produce a behavioral state in healthy
      volunteers that resembles some aspects of schizophrenia. A dysfunction in NMDA
      dopaminergic interactions has been proposed as a mechanism for these behavioral
      effects. In this study, we examined the effects of ketamine on striatal dopamine
      release in healthy human subjects with a novel 11C-raclopride/PET displacement
      paradigm and compared these effects to administration of saline and the direct
      acting dopamine agonist amphetamine. We found that the percent decreases (mean +/
      SD) in specific 11C-raclopride binding from baseline for ketamine (11.2 +/- 8.9)
      was greater than for saline (1.9 +/- 3.7) (t = 2.4, df = 13, P = 0.003)
      indicating that ketamine caused increases in striatal synaptic dopamine
      concentrations. Ketamine-related binding changes were not significantly different
      than the decreases in percent change (mean +/- SD) in specific 11C-raclopride
      binding caused by amphetamine (15.5 +/- 6.2) (t = 1.3, df = 19, P = 0.21).
      Ketamine-induced changes in 11C-raclopride-specific binding were significantly
      correlated with induction of schizophrenia-like symptoms. The implications of
      this brain imaging method for studies of schizophrenia and the mechanism of
      action of antipsychotic drugs are discussed.

PMID- 9593105
TI  - Activating properties of cocaine and cocaethylene in a behavioral preparation of
      Drosophila melanogaster.
AB  - The use of Drosophila as a model to study the behavioral consequences of
      stimulant drugs was analyzed in an active preparation of decapitated Drosophila.
      Application of cocaine and cocaethylene to discrete nerve cord cells regulating
      motor programs of behavior produced striking patterns of behavioral activity in a
      concentration-related manner. In general, intense circling behavior and
      significant wing buzzing activity were distinguishable behavioral markers in
      flies treated with mM concentrations of cocaine or cocaethylene. The significant
      changes in motor behavior induced by stimulant drugs in decapitated flies were
      not reproduced by the application of apomorphine, a direct dopamine (DA) agonist,
      or octopamine, a naturally occurring transmitter in arthropods. Because both
      cocaine and cocaethylene interfere with DA reuptake in mammals, we characterized
      the role of DA receptors mediating increased stereotypy and motor behavior in
      flies. Coadministration of SCH-23390, a specific D1 receptor antagonist,
      significantly attenuated the behavior-activating properties of cocaine and
      cocaethylene in this active experimental preparation. Therefore, the receptor
      protein mediating the behavioral responses to stimulant drugs in Drosophila is
      pharmacologically similar to the mammalian D1 subtype. In rats, cocaine- and
      cocaethylene-induced behavioral activity is complex, with increasing evidence
      that the D1 receptor interacts significantly with N-methyl-D-aspartate (NMDA)
      receptor pathways to produce an altered behavioral phenotype. To further
      characterize additional receptor subtypes targeted by the actions of cocaine and
      cocaethylene, we pretreated flies with MK-801 and dextromethorphan. Both of these
      drugs are potent, selective noncompetitive NMDA receptor antagonists.
      Interestingly, MK-801 and dextromethorphan profoundly reduced the behavior
      activating properties of cocaine and cocaethylene in Drosophila. Therefore, as in
      rats, the NMDA (and D1) receptor pathways in this arthropod represent obligatory
      targets for the behavioral effects of stimulant drugs.

PMID- 9593106
TI  - Enantioselective modulation of GABAergic synaptic transmission by steroids and
      benz[e]indenes in hippocampal microcultures.
AB  - The effects of enantiomers of the neurosteroid analogues, 3alpha-hydroxy-5alpha
      pregnan-20-one (DHP) and 3alpha-hydroxy-5alpha-androstane-17beta-carbonitrile
      (ACN), and the benz[e]indene, BI-1, on synaptic currents were examined in
      microcultures of rat hippocampal neurons. Over the range of 0.1-10 microM, the
      (+)-enantiomers were more potent and effective than their (-)-enantiomeric
      counterparts in enhancing gamma-aminobutyric acid (GABA)A receptor-mediated
      evoked synaptic currents. The (+)-enantiomers had small effects on peak currents,
      but slowed the decay of inhibitory synaptic currents, resulting in 2-3-fold
      increases in charge transfer during inhibitory synaptic events at 10 microM.
      Similar prolongations of spontaneous miniature inhibitory postsynaptic currents
      (IPSCs) and responses to brief GABA pulses to outside-out patches suggest that
      the prolongations of evoked synaptic currents result primarily from postsynaptic
      effects. In contrast, the (-)-enantiomers had little effect on evoked IPSCs at
      concentrations < or = 1 microM, but enhanced inhibitory transmission at 10
      microM. At concentrations < or = 1 microM, neither the (+)- nor (-)-enantiomers
      altered glutamate-mediated excitatory synaptic currents. At 10 microM, (+)-DHP
      and (+)-ACN depressed excitatory responses in a bicuculline-sensitive fashion,
      suggesting that direct chloride channel gating by the steroids contributed to the
      depression. These data indicate that certain steroids and benz[e]indenes augment
      inhibitory synaptic transmission enantioselectively and provide strong support
      for the hypothesis that steroids act at specific sites on synaptic GABA(A)
      receptors rather than via alteration of membrane lipids.

PMID- 9593107
TI  - Autoradiographic and SPECT imaging of cerebral opioid receptors with an iodine
      123 labeled analogue of diprenorphine.
AB  - The feasibility of imaging cerebral opioid receptors by single photon emission
      computed tomography (SPECT) has been established in baboon using a novel analog
      of diprenorphine (DPN) radiolabeled with iodine-123. The radioligand, [123I]-O-IA
      DPN (C6-O-[123I]iodoallyl-DPN), was prepared in good yield (80%) with high
      radiochemical purity (>97%) and high specific radioactivity (>2,400
      mCi/micromol). In ex vivo autoradiographic studies, with and without naltrexone
      blockade, [123I]-O-IA-DPN specifically labeled opioid receptors throughout the
      mouse brain. Nonmetabolized radioligand accounted for >90% of the signal observed
      in extracts of whole mouse brain. SPECT imaging trials showed that [123I]-O-IA
      DPN selectively localized in regions of baboon brain known to have high densities
      of opioid receptors, such as striatum, thalamus, and temporal cortex. A much
      lower level of radioligand uptake and retention was noted for cerebellum, a
      region with few opioid binding sites. Pretreatment with naltrexone (6.5 pmol/kg)
      blocked [123I]-O-IA-DPN binding in all brain regions. Using naltrexone blockade
      to define the nonspecific component for a given region of interest, total to
      nonspecific binding ratios increased linearly (r > or = 0.98) over the SPECT
      study with maximal values for striatum (9.8), thalamus (7.1), and temporal cortex
      (6.9) reached at the last time point investigated (3.5 h). Specific binding for
      these regions, assessed as the difference between regional SPECT activity for the
      control and blocked states, proved irreversible over the observation period. By
      the end of the time course, specific [123I]-O-IA-DPN binding was >85% of total
      radioactivity in regions rich in opioid receptors and 62% of total radioactivity
      in cerebellum. The aggregate data are consistent with visualization of multiple
      opioid receptor types. Thus, [123I]-O-IA-DPN should prove useful for SPECT
      studies within the constraints imposed by a lack of innate selectivity for a
      single type of brain opioid receptor.

PMID- 9593108
TI  - In vivo detection of short- and long-term MDMA neurotoxicity--a positron emission
      tomography study in the living baboon brain.
AB  - The present study evaluated short- and long-term effects of MDMA (3,4
      methylenedioxymethamphetamine) in the baboon brain using PET and [11C](+)McN
      5652, a potent 5-HT transporter ligand, as well as [11C]RTI-55, a cocaine
      derivative which labels both 5-HT and dopamine transporters. Following baseline
      PET scans with [11C](+)McN5652, [11C](-)McN5652 (the inactive enantiomer of the
      active enantiomer [11C](+)McN5652) and [11C]RTI-55, a baboon was treated with
      MDMA (5 mg/kg, s.c., twice daily for four consecutive days). PET studies at 13,
      19, and 40 days post-MDMA revealed decreases in mean radioactivity levels in all
      brain regions when using [11C](+)McN 5652, but not with [11C](-)McN5652 or
      [11C]RTI-55. Reductions in specific [11C](+)McN5652 binding (calculated as the
      difference in radioactivity concentrations between (+) and (-)[11C]McN5652)
      ranged from 44% in the pons to 89% in the occipital cortex. PET studies at 9 and
      13 months showed regional differences in the apparent recovery of 5-HT
      transporters, with increases in some brain regions (e.g., hypothalamus) and
      persistent decreases in others (e.g., neocortex). Data obtained from PET studies
      correlated well with regional 5-HT axonal marker concentrations in the CNS
      measured after sacrifice of the animal. The results of these studies indicate
      that PET imaging of the living nonhuman primate brain with [11C](+)McN5652 can
      detect changes in regional 5-HT transporter density secondary to MDMA-induced
      neurotoxicity. Using PET, it should also be feasible to use [11C](+)McN5652 to
      determine whether human MDMA users are also susceptible to MDMA's neurotoxic
      effects.

PMID- 9593109
TI  - Validity of family history for the diagnosis of dementia among siblings of
      patients with late-onset Alzheimer's disease.
AB  - We examined 180 siblings of 127 probands with probable or possible Alzheimer's
      dementia (AD) in a family study of AD. The overall sensitivity of a simple family
      history questionnaire was 64% and the specificity was 84%. Sensitivity improved
      90-100% with minimal decline in specificity when we considered clinic-based vs.
      population survey patients. Higher education among informants and the
      availability of a spouse or a sibling as informant significantly increased
      sensitivity. Awareness of such factors may improve the yield of the family
      history in AD using a simple questionnaire.

PMID- 9593110
TI  - National database of familial cancer in Sweden.
AB  - A family cancer database was constructed from the nationwide Swedish registries
      and includes approximately 6 million persons and >30,000 cancers in offspring
      diagnosed at ages 15-51 years and their parents. A particular advantage of the
      database is that the contribution of both parental lineages on cancer risk can be
      examined. Cancer risk in the offspring was increased approximately 1.1 times when
      the father had cancer, and no increase was noted when the mother had cancer. If
      both parents had cancer, the risk for sons was 1.4 and for daughters 1.3. The
      sites of increased cancer risk in the offspring were colorectum, breast, cervix,
      corpus uteri, ovary, testis, melanoma, eye, other endocrine glands, and multiple
      myeloma. The results among young and middle-age adults suggest that cancer in
      both parents increases the cancer risk in the offspring at many sites. The
      molecular genetic explanation may be that rare dominant single genes increase
      susceptibility at many sites, or that overlapping sets of genes control
      susceptibility at multiple sites.

PMID- 9593111
TI  - Major locus influencing plasma APO-A1 levels also controls plasma HDL3-C
      concentrations.
AB  - Elevated plasma levels of apolipoprotein A1 (APO-A1) and high-density lipoprotein
      cholesterol (HDL-C) are important protective factors for atherosclerosis and
      coronary heart disease. Using the data on plasma concentrations of APO-A1, and
      HDL-C particles HDL2-C and HDL3-C in 970 Israeli individuals belonging to 228
      pedigrees, we tested the hypothesis that a major locus influencing
      interindividual variation in APO-A1 levels also controls interindividual
      variation in HDL3-C and HDL2-C levels. Univariate and bivariate complex
      segregation analyses, as implemented in two statistical packages (MAN-3 and PAP
      4.0) were applied to test the hypothesis. The results of the analysis clearly
      indicated the possibility of major gene involvement in the determination of
      plasma concentration variation of each of the 3 study variables. The results
      provide strong evidence in support of our hypothesis that HDL3-C genetic
      variation fully depends on the APO-A1 major locus. In particular, environmental
      and sporadic models were strongly rejected (P < 0.001) in bivariate analysis. The
      hypothesis of no pleiotropic effect of the putative APO-A1 locus on HDL3-C
      transmission was also unequivocally rejected (P < 0.001), while the bivariate
      Mendelian model was accepted (P > 0.05). The results of bivariate analysis of APO
      A1 effect on HDL2-C were not clear. They indicated the possibility of the
      existence of slight genetic covariation between the two variables, and as yet we
      were unable to decipher the mode of covariation with the applied models.

PMID- 9593112
TI  - Environmental factors can confound identification of a major gene effect: results
      from a segregation analysis of a simulated population of lung cancer families.
AB  - Proper control of environmental factors can be crucial to the identification of
      genes that influence susceptibility to a complex trait, especially for a trait
      such as lung cancer, for which the environmental factor (smoking) accounts for a
      significant etiologic fraction of the disease. An earlier segregation analysis of
      337 Louisiana families, which incorporated direct measure of tobacco consumption,
      provided evidence for autosomal codominant inheritance of a major gene that
      influenced age at onset of lung cancer. Subsequent analyses were performed in
      which the families were stratified into two subsets based on birth cohort of the
      proband; results suggested the presence of heterogeneity that were postulated to
      reflect the influence of cohort trends in tobacco consumption. To evaluate this
      hypothesis further, we simulated a population of three-generation pedigrees in
      which an autosomal dominant mode of susceptibility to lung cancer was
      transmitted, but tobacco use varied across generations corresponding to published
      trends in smoking. A total of 200,000 individuals in families of various sizes,
      ages, and cigarette smoking habits were simulated from 1900 to 1980. From this
      population, 324 families (2,405 individuals) with 380 cases of lung cancer were
      ascertained through 328 lung cancer probands. Complex segregation analysis was
      performed using the REGTL program of S.A.G.E. in which pack-years of tobacco
      exposure were incorporated directly into the likelihood calculations. Although
      the no major gene, environmental, and Mendelian recessive hypotheses were
      rejected, both dominant and codominant transmission provided a good fit to the
      data. Thus in a population of simulated families with autosomal dominant
      susceptibility to lung cancer, intergenerational differences in tobacco
      consumption led to the detection of autosomal codominant transmission as an
      acceptable hypothesis. These results underscore the potential danger of
      segregation analysis of complex traits in which exposure to known environmental
      influences may differ across generations.

PMID- 9593113
TI  - Testing causal hypotheses in multivariate linkage analysis of quantitative
      traits: general formulation and application to sibpair data.
AB  - We provide a general framework for the development of model-free methods for the
      linkage analysis of multivariate phenotypic data. It is possible within this
      framework to test both for linkage of a set of phenotypes to one or more markers
      and for the presence of structural relations among the phenotypes themselves.
      This report presents the general model, paying special attention to the
      assumptions that enter its formulation, and outlines the estimation procedures
      that may be used.

PMID- 9593114
TI  - Semiparametric estimation of major gene effects for age of onset.
AB  - Analysis of age of onset is a key factor in the segregation and linkage analysis
      of some complex genetic traits. Previous work in the genetics literature has used
      parametric distributional assumptions on age of onset. In this paper, a Cox model
      with latent major gene effects is used: a semiparametric model with unspecified
      baseline hazard. A Monte Carlo EM procedure is used to obtain maximum likelihood
      estimates. Markov chain Monte Carlo is used to realize genotypic configurations
      from the posterior distribution given the current model and the observed data,
      and these genotypic configurations are used to estimate the expectations in the
      EM algorithm. Simulated data sets indicate that the parameters can be estimated
      well, and one real data set shows the practical applicability of the proposed
      method.

PMID- 9593115
TI  - Analytic strategies to detect linkage to a common disorder with genetically
      determined age of onset: diabetes mellitus in Pima Indians.
AB  - Segregation analysis suggests that the high prevalence of non-insulin-dependent
      diabetes mellitus in Pima Indians may be partially due to a single locus with a
      major effect on age of onset. A simulation study was conducted to evaluate the
      power of various age-adjustment strategies in linkage analysis to detect this
      putative gene in 1,862 sib-pairs from 264 potentially informative nuclear
      families. Simulations were performed at a recombination fraction (theta) of 0.05
      for values of polymorphism information content (PIC) ranging from 0.38 to 1.00.
      Under the codominant age-of-onset model supported by segregation analysis, power
      to detect linkage (at P < 0.0001) at PIC = 1.00 was 75% for the Haseman-Elston
      (HE) sib-pair test and 63% for the affected sib-pair test (ASP) with no age
      adjustment. Substantial improvements in power were possible for the HE test by
      defining the trait as a survival analysis "residual" (power = 91%) and for the
      ASP test by use of an age-of-onset threshold above which individuals are not
      included in the analysis (power = 90%, for age of onset < 45 yrs). The parametric
      method of linkage analysis was most powerful, as long as both the analysis model
      and the simulation model involved a genetic effect on age of onset, regardless of
      whether dominance at the trait locus was misspecified. Methods of age adjustment
      based on the probability of eventually becoming affected only improved power when
      the genetic effect was on susceptibility rather than age of onset. The method of
      age adjustment in linkage analysis may depend on whether one anticipates a
      genetic effect primarily on age of onset or on ultimate susceptibility.

PMID- 9593117
TI  - Characteristics and dynamics of bacterial populations during postantibiotic
      effect determined by flow cytometry.
AB  - Changes in bacterial ultrastructure after antibiotic exposure and during the
      postantibiotic effect (PAE) have been demonstrated by electron microscopy (EM).
      However, EM is qualitative and subject to individual interpretation. In contrast,
      flow cytometry gives qualitative and quantitative information. The sizes and
      nucleic acid contents of Escherichia coli and Pseudomonas aeruginosa were studied
      during antimicrobial exposure as well as during the PAE period by staining the
      organisms with propidium iodide and analyzing them with flow cytometry and
      fluorescence microscopy. The effects of ampicillin, ceftriaxone, ciprofloxacin,
      gentamicin, and rifampin were studied for E. coli, whereas for P. aeruginosa
      imipenem and ciprofloxacin were investigated. After exposure of E. coli to
      ampicillin, ceftriaxone, and ciprofloxacin, filamentous organisms were observed
      by fluorescence microscopy. These changes in morphology were reflected by
      increased forward light scatter (FSC) and nucleic acid content as measured by
      flow cytometry. For the beta-lactams the extent of filamentation increased in a
      dose-dependent manner after drug removal, resulting in formation of distinct
      subpopulations of bacteria. These changes peaked at 20 to 35 min, and bacteria
      returned to normal after 90 min after drug removal. In contrast, the
      subpopulations induced by ciprofloxacin did not return to normal until > 180 min
      after the end of the classically defined PAE. Rifampin resulted in formation of
      small organisms with low FSC, whereas no distinctive characteristics were noted
      after gentamicin exposure. For P. aeruginosa an identifiable subpopulation of
      large globoid cells and increased nucleic acid content was detected after
      exposure to imipenem. These changes persisted past the PAE, as defined by
      viability counting. Swollen organisms with increased FSC were detected after
      ciprofloxacin exposure, even persisting during bacterial growth. In summary, for
      beta-lactam antibiotics and ciprofloxacin, the PAE is characterized by dynamic
      formation of enlarged cell populations of increased nucleic acid content, whereas
      rifampin induces a decrease in size and nucleic acid content in the organisms.
      Flow cytometry is an ideal method for future studies of bacterial phenotypic
      characteristics during the PAE.

PMID- 9593116
TI  - Prevention of infection due to Pneumocystis carinii.

PMID- 9593118
TI  - Field evaluation of the prophylactic effect of an isometamidium sustained-release
      device against trypanosomiasis in cattle.
AB  - In order to compare the prophylactic effect provided by a poly(D,L-lactide)
      sustained-release device (SRD) containing isometamidium (ISMM) with that provided
      by the classical intramuscular injection of the drug, a field trial was carried
      out at the Madina Diassa Ranch in Mali. One- to 3-year-old N'Dama cattle were
      randomly divided into three groups. The first group (n = 42) was treated with
      ISMM at a dose of 1 mg/kg of body weight, the second group (n = 44) received the
      same dose of the drug via an SRD, which was subcutaneously implanted in the
      shoulder region, and the third group (n = 36) was kept as an untreated control
      group. All animals were treated with diminazene aceturate (7 mg/kg of body
      weight) 2 weeks before the start of the experiment and were tested monthly by the
      buffy coat technique for a period of 8 months. Glossina morsitans submorsitans
      was the most important tsetse species, with apparent densities (number of
      catches/trap/day) varying between 11.9 and 38.7 over the experimental period.
      Eight months after treatment the cumulative infection rates were 27.7, 58.5, and
      77.4% in the group with the SRD implant, the group receiving the intramuscular
      injection, and the control group, respectively. Statistical analysis showed that
      the incidence of trypanosomiasis was significantly lower (P = 0.006) in the group
      which received ISMM via the SRD than in the one which was treated with ISMM
      intramuscularly.

PMID- 9593119
TI  - Biological characterization of endotoxins released from antibiotic-treated
      Pseudomonas aeruginosa and Escherichia coli.
AB  - The supernatants taken from Pseudomonas aeruginosa and Escherichia coli cultures
      in human sera or chemically defined M9 medium in the presence of ceftazidime
      (CAZ) contained high levels of endotoxin, while those taken from the same
      cultures in the presence of imipenem (IPM) yielded a very low level of endotoxin.
      The biological activities of endotoxin in the supernatants were compared with
      those of phenol water-extracted lipopolysaccharide (LPS). The endotoxin released
      from the organisms as a result of CAZ treatment (CAZ-released endotoxin)
      contained a large amount of protein. The protein, however, lacked endotoxic
      activity, since the endotoxin did not show any in vivo toxic effects in LPS
      hyporesponsive C3H/HeJ mice sensitized with D-(+)-galactosamine (GalN) or any
      activation of C3H/HeJ mouse macrophages in vitro. The activities of CAZ- and IPM
      released endotoxin (as assessed by a chromogenic Limulus test) were fundamentally
      the same as those of P. aeruginosa LPS, since their regression lines were
      parallel. The CAZ-released endotoxin was similar to purified LPS with respect to
      the following biological activities in LPS-responsive C3H/HeN mice and LPS
      hyporesponsive C3H/HeJ mice: lethal toxicity in GalN-sensitized mice, in vitro
      induction of tumor necrosis factor- and NO production by macrophages, and mitogen
      activated protein kinase activation in macrophages. The macrophage activation by
      CAZ-released endotoxin as well as LPS was mainly dependent on the presence of
      serum factor and CD14 antigen. Polymyxin B blocked the activity. These findings
      indicate that the endotoxic activity of CAZ-released endotoxin is due primarily
      to LPS (lipid A).

PMID- 9593121
TI  - In vitro susceptibilities of aerobic and facultative non-spore-forming gram
      positive bacilli to HMR 3647 (RU 66647) and 14 other antimicrobials.
AB  - The comparative in vitro activity of the ketolide HMR 3647 (RU 66647) and those
      of structurally related macrolide-lincosamide-streptogramin compounds
      (erythromycin, roxithromycin, azithromycin, clarithromycin, josamycin,
      lincomycin, pristinamycin, and quinupristin-dalfopristin) as well as those of
      benzylpenicillin, doxycycline, vancomycin, teicoplanin, levofloxacin, and
      rifapentine against 247 aerobic and facultative non-spore-forming gram-positive
      bacilli were determined by an agar dilution method. The ketolide was active
      against most organisms tested except Corynebacterium striatum, coryneform CDC
      group 12, and Oerskovia spp. The frequency of resistance to erythromycin and
      other macrolides as well as that to lincomycin was high. Pristinamycin and, to a
      lesser extent, quinupristin-dalfopristin were very active, but resistance to
      these agents was present in some strains of Rhodococcus equi, Listeria spp., C.
      striatum, Erysipelothrix rhusiopathiae, and Oerskovia spp. HMR 3647 was very
      active against all erythromycin-sensitive and many erythromycin-nonsusceptible
      strains, especially Corynebacterium minutissimum, Corynebacterium
      pseudodiphtheriticum, Corynebacterium amycolatum, and Corynebacterium jeikeium.
      In vitro resistance to benzylpenicillin was common, but doxycycline, vancomycin,
      and teicoplanin were very active against most organisms tested except E.
      rhusiopathiae, against which glycopeptide antibiotics were not active. The in
      vitro activity of levofloxacin was remarkable, but resistance to this agent was
      common for C. amycolatum, Corynebacterium urealyticum, C. jeikeium, and Oerskovia
      spp. strains. Rifapentine was also very active in vitro against many organisms,
      but resistance to this agent was always present in E. rhusiopathiae and was very
      common in C. striatum and C. urealyticum.

PMID- 9593120
TI  - Modulation of gyrase-mediated DNA cleavage and cell killing by ATP.
AB  - An uncoupler of oxidative phosphorylation, 2,4-dinitrophenol, and an aconitase
      inhibitor, fluoroacetic acid, both of which are known to lower the cellular ATP
      pool, protected Escherichia coli cells from the bactericidal actions of gyrase
      poisons including quinolone antibiotics, nalidixic acid and ciprofloxacin, and
      the epipodophyllotoxins VP-16 and VM-26. Using purified E. coli DNA gyrase, we
      examined the effect of ATP on gyrase-mediated DNA cleavage in the presence of
      these gyrase poisons. ATP was shown to stimulate gyrase-mediated DNA cleavage
      from 10- to more than 100-fold in the presence of these gyrase poisons. ADP
      antagonized the stimulatory effect of ATP. Consequently, gyrase-mediated DNA
      cleavage induced by gyrase poisons is modulated by the ATP concentration/ADP
      concentration ([ATP]/[ADP]) ratio. Coumermycin A1, an inhibitor of the ATPase
      subunit of DNA gyrase, like ADP, also effectively antagonized the stimulatory
      effect of ATP on gyrase-mediated DNA cleavage induced by gyrase poisons.
      Furthermore, coumermycin A1, like DNP and fluoroacetic acid, also protected cells
      from the bactericidal action of gyrase poisons. In the aggregate, our results are
      consistent with the notion that the [ATP]/[ADP] ratio, through its modulatory
      effect on the gyrase-mediated DNA cleavage, is an important determinant of
      cellular susceptibility to gyrase poisons.

PMID- 9593122
TI  - Identification of Saccharomyces cerevisiae genes conferring resistance to
      quinoline ring-containing antimalarial drugs.
AB  - To identify genes that can confer resistance to antimalarial drugs in yeast, we
      transformed the quinidine-sensitive strain CYX247-9A of Saccharomyces cerevisiae
      with a yeast genomic library and selected for transformants that grow in the
      presence of elevated levels of antimalarial drugs. Plasmids were rescued from
      such clones and were analyzed for the presence of individual open reading frames
      that can confer drug resistance. Using quinidine as the selective drug, we were
      able to identify three genes that can cause resistance to antimalarial drugs.
      Overexpression of the yeast genes CIN5 (a member of the family of bZIP
      transcription factors), STII (a Hsp90 cochaperone), and YOR273c (a member of the
      major facilitator superfamily of transmembrane transporters) conferred 3.9-, 7.0
      , and 4.3-fold resistance to quinidine, respectively, over that of control yeast.
      Cross-resistance assays determined that STI1 also conferred resistance to
      mefloquine (3.4-fold), while CIN5 also conferred resistance to mefloquine (9.6
      fold) and chloroquine (5.4-fold). Using mefloquine as the selective drug, we
      determined that overexpression of YBR233w, a member of the hnRNPK family of
      nuclear RNA binding proteins, conferred resistance to mefloquine (13.5-fold).
      Expression of the human hnRNPK homolog of YBR233w in S. cerevisiae also conferred
      mefloquine resistance, suggesting that homologs of the identified resistance
      genes may perform similar functions in species other than yeast. Our experiments
      have identified heretofore unknown pathways of resistance to quinoline ring
      containing antimalarial drugs in S. cerevisiae.

PMID- 9593123
TI  - A237T as a modulating mutation in naturally occurring extended-spectrum TEM-type
      beta-lactamases.
AB  - A TEM-1 beta-lactamase derivative containing the single amino acid substitution
      A237T slightly increased (from 24 to 32 microg/ml) the cephalothin MIC for
      Escherichia coli RYC1000 but did not influence the activities of cefotaxime,
      ceftazidime, and aztreonam (MICs of 0.03, 0.12, and 0.06 microg/ml,
      respectively). Despite its apparent neutrality, addition of the A237T mutation to
      the pair of mutations characterizing TEM-10 (R164S and E240K) had a strong effect
      on substrate preference. Ceftazidime and aztreonam MICs decreased from 128 and 16
      microg/ml to 16 and 2 microg/ml, respectively. In contrast, the cefotaxime MIC
      increased from 0.5 to 4 microg/ml. The acquisition of apparently neutral or even
      deleterious mutations results in a very effective mechanism of resistance to
      different beta-lactams that may be simultaneously or subsequently present in the
      environment. We propose here that the mutation in position 237 is an example of a
      modulating mutation and that consideration of this type of mutation may be
      important for understanding the evolution of beta-lactamases.

PMID- 9593124
TI  - Metabolism in human cells of the D and L enantiomers of the carbocyclic analog of
      2'-deoxyguanosine: substrate activity with deoxycytidine kinase, mitochondrial
      deoxyguanosine kinase, and 5'-nucleotidase.
AB  - The carbocyclic analog of 2'-deoxyguanosine (CdG) has broad-spectrum antiviral
      activity. Because of recent observations with other nucleoside analogs that
      biological activity may be associated the L enantiomer rather than, as expected,
      with the D enantiomer, we have studied the metabolism of both enantiomers of CdG
      to identify the enzymes responsible for the phosphorylation of CdG in noninfected
      and virally infected human and duck cells. We have examined the enantiomers as
      substrates for each of the cellular enzymes known to catalyze phosphorylation of
      deoxyguanosine. Both enantiomers of CdG were substrates for deoxycytidine kinase
      (EC 2.7.1.74) from MOLT-4 cells, 5'-nucleotidase (EC 3.1.3.5) from HEp-2 cells,
      and mitochondrial deoxyguanosine kinase (EC 2.7.1.113) from human platelets and
      CEM cells. For both deoxycytidine kinase and mitochondrial deoxyguanosine kinase,
      the L enantiomer was the better substrate. Even though the D enantiomer was the
      preferred substrate with 5'-nucleotidase, the rate of phosphorylation of the L
      enantiomer was substantial. The phosphorylation of D-CdG in MRC-5 cells was
      greatly stimulated by infection with human cytomegalovirus. The fact that the
      phosphorylation of D-CdG was stimulated by mycophenolic acid and was not affected
      by deoxycytidine suggested that 5'-nucleotidase was the enzyme primarily
      responsible for its metabolism in virally infected cells. D-CdG was extensively
      phosphorylated in duck hepatocytes, and its phosphorylation was not affected by
      infection with duck hepatitis B virus. These results are of importance in
      understanding the mode of action of D-CdG and related analogs and in the design
      of new biologically active analogs.

PMID- 9593125
TI  - In vitro activities of benzimidazoles against Echinococcus multilocularis
      metacestodes.
AB  - Alveolar echinococcosis, caused by the larval (metacestode) stage of the tapeworm
      Echinococcus multilocularis, is a lethal parasitosis of the liver prevalent in
      the Northern Hemisphere. For chemotherapy the benzimidazole derivatives
      mebendazole and albendazole were introduced, and their use has resulted in a
      significant improvement in the survival rates. However, data from experiments
      with animals and clinical observations indicate that these drugs elicit only
      parasitostatic activity and in most cases are not able to completely eliminate
      the parasitic metacestode tissue. In the present study, we applied a culture
      system for the in vitro growth and proliferation of E. multilocularis
      metacestodes to analyze the parasitostatic and parasitocidal potential of
      mebendazole. Here, we demonstrate for the first time that at concentrations of
      >0.1 microM, i.e., at concentrations used for therapy of human alveolar
      echinococcosis, this antihelminth drug is parasitocidal in vitro. Viability
      assessment was performed by infection experiments with Meriones unguiculatus and
      mebendazole-treated metacestode tissue and by reverse transcription-PCR for the
      detection of E. multilocularis mRNA. The E. multilocularis in vitro model proved
      to be a valuable tool for the analysis of the potential of antihelminth drugs.

PMID- 9593126
TI  - In vitro activities of terbinafine against cutaneous isolates of Candida albicans
      and other pathogenic yeasts.
AB  - Terbinafine is active in vitro against a wide range of pathogenic fungi,
      including dermatophytes, molds, dimorphic fungi, and some yeasts, but earlier
      studies indicated that the drug had little activity against Candida albicans. In
      contrast, clinical studies have shown topical and oral terbinafine to be active
      in cutaneous candidiasis and Candida nail infections. In order to define the anti
      Candida activity of terbinafine, we tested the drug against 350 fresh clinical
      isolates and additional strains by using a broth dilution assay standardized
      according to the guidelines of the National Committee for Clinical Laboratory
      Standards (NCCLS) M27-A assay. Terbinafine was found to have an MIC of 1
      microg/ml for reference C. albicans strains. For 259 clinical isolates, the MIC
      at which 50% of the isolates are inhibited (MIC50) of terbinafine was 1 microg/ml
      (fluconazole, 0.5 microg/ml), and the MIC90 was 4 microg/ml (fluconazole, 1
      microg/ml). Terbinafine was highly active against Candida parapsilosis (MIC90,
      0.125 microg/ml) and showed potentially interesting activity against isolates of
      Candida dubliniensis, Candida guilliermondii, Candida humicola, and Candida
      lusitaniae. It was not active against the Candida glabrata, Candida krusei, and
      Candida tropicalis isolates in this assay. Cryptococcus laurentii and
      Cryptococcus neoformans were highly susceptible to terbinafine, with MICs of 0.06
      to 0.25 microg/ml. The NCCLS macrodilution assay provides reproducible in vitro
      data for terbinafine against Candida and other yeasts. The MICs for C. albicans
      and C. parapsilosis are compatible with the known clinical efficacy of
      terbinafine in cutaneous infections, while the clinical relevance of its
      activities against the other species has yet to be determined.

PMID- 9593127
TI  - Sulfonamide resistance in Streptococcus pyogenes is associated with differences
      in the amino acid sequence of its chromosomal dihydropteroate synthase.
AB  - Sulfonamide resistance in recent isolates of Streptococcus pyogenes was found to
      be associated with alterations of the chromosomally encoded dihydropteroate
      synthase (DHPS). There were 111 different nucleotides (13.8%) in the genes found
      in susceptible and resistant isolates, respectively, resulting in 30 amino acid
      changes (11.3%). These substantial changes suggested the possibility of a foreign
      origin of the resistance gene, in parallel to what has already been found for
      sulfonamide resistance in Neisseria meningitidis. The gene encoding DHPS was
      linked to at least three other genes encoding enzymes of the folate pathway.
      These genes were in the order GTP cyclohydrolase, dihydropteroate synthase,
      dihydroneopterin aldolase, and hydroxymethyldihydropterin pyrophosphokinase. The
      nucleotide differences in genes from resistant and susceptible strains extended
      from the beginning of the GTP cyclohydrolase gene to the end of the gene encoding
      DHPS, an additional indication for gene transfer in the development of
      resistance. Kinetic measurements established different affinities for
      sulfathiazole for DHPS enzymes isolated from resistant and susceptible strains.

PMID- 9593129
TI  - Five-day cefdinir treatment for streptococcal pharyngitis. Cefdinir Pharyngitis
      Study Group.
AB  - A multicenter, randomized, controlled, investigator-blind study was performed to
      evaluate the safety and efficacy of oral cefdinir versus oral penicillin V for
      the treatment of pharyngitis due to group A beta-hemolytic streptococci (GABHS).
      Patients 13 years of age and older were randomized to receive either oral
      cefdinir (300 mg twice a day) for 5 days followed by placebo for 5 days or oral
      penicillin V (250 mg four times a day) for 10 days. Throat cultures were
      obtained, and signs and symptoms of pharyngitis were recorded at study admission
      and follow-up visits on study days 11 to 15, 16 to 20, and 25 to 31. Patients
      kept a diary to record medication intake and their assessment of throat pain at
      admission and at each day of study treatment. Five hundred fifty-eight patients
      were enrolled, of whom 432 (77.4%) were clinically and microbiologically
      evaluable. The GABHS eradication rates 5 to 10 days after completion of therapy
      were 193 of 218 (88.5%) in the cefdinir group and 176 of 214 (82.2%) in the
      penicillin group (P = 0.053). Clinical cure rates were 89.0 and 84.6%,
      respectively (P = 0.80). By the time of the long-term follow-up visit, 2 to 3
      weeks after completion of treatment, 156 of 191 (81.7%) of the assessable
      cefdinir patients and 152 of 195 (77.9%) of the penicillin patients remained free
      of GABHS. Both treatments were well tolerated, with adverse reaction rates of
      18.3% in the cefdinir study arm and 15.0% in the penicillin study arm (P =
      0.278). Five-day treatment with cefdinir is safe and effective therapy for GABHS
      pharyngitis. Based on its twice-a-day dosage and shorter course of therapy,
      leading to potentially greater patient compliance, cefdinir may be considered for
      use in the treatment of pharyngitis caused by GABHS.

PMID- 9593128
TI  - Drug evaluation of concurrent Pneumocystis carinii, Toxoplasma gondii, and
      Mycobacterium avium complex infections in a rat model.
AB  - We present a new experimental model for the simultaneous evaluation of the
      activities of drugs against Pneumocystis carinii, Toxoplasma gondii, and
      Mycobacterium avium complex infections. Rats latently infected with P. carinii
      were challenged with the MO-1 strain of M. avium and then immunosuppressed with
      corticosteroids for 7 weeks. At week 5 the RH strain of T. gondii was
      intraperitoneally injected. Organs were examined for the three pathogens after
      death or killing of the animals at week 7. Without treatment, rats challenged
      with T. gondii died with pulmonary P. carinii infection and disseminated T.
      gondii and M. avium infections. In order to assess the value of the model for
      evaluation of the activities of drugs, we administered by oral gavage for 7 weeks
      drugs or combinations of drugs selected for their individual efficacies against
      at least one pathogen. We found that clarithromycin with sulfamethoxazole,
      clarithromycin with atovaquone, roxithromycin with sulfamethoxazole or dapsone,
      and rifabutin with atovaquone were effective against the three infections,
      whereas PS-15 with dapsone and trimethoprim with sulfamethoxazole were active
      against Toxoplasma and Pneumocystis infections only. This triple-infection rat
      model offers a new tool for the simultaneous evaluation of the activities of
      drugs against three of the major opportunistic infections occurring in
      immunosuppressed individuals.

PMID- 9593130
TI  - Characterization of the antimonial antileishmanial agent meglumine antimonate
      (glucantime).
AB  - Meglumine antimonate (Glucantime), a drug of choice for the treatment of
      leishmaniasis, is produced by the reaction of pentavalent antimony with N-methyl
      D-glucamine, a carbohydrate derivative. We investigated the structure and
      composition of meglumine antimonate, which remain poorly understood, despite 50
      years of use. Measurement of the antimony content of meglumine antimonate powder
      indicated a 1:1.37 molar ratio of antimony to N-methyl-D-glucamine. Osmolality
      measurements performed with meglumine antimonate solutions demonstrated an
      average of 1.43 antimony atoms per molecule of meglumine antimonate. The
      osmolality of a 1:10 dilution of stock meglumine antimonate increased by 45% over
      8 days, suggesting hydrolysis to less complex species. A comparison of the proton
      nuclear magnetic resonance spectra of N-methyl-D-glucamine and meglumine
      antimonate revealed an increase in complexity in the latter but with all of the
      resonances of the former still being evident, consistent with the presence of
      coordination complexes between antimony and each of the N-methyl-D-glucamine
      hydroxyls. Fast atom bombardment and electrospray ionization mass spectrometry
      coupled with several derivatization procedures provided evidence that up to four
      N-methyl-D-glucamine hydroxyls are coordinated with each antimony. A series of
      oligomers were observed. The major moiety has a molecular mass of 507 atomic mass
      units and consists of NMG-Sb-NMG, where Sb represents antimony and NMG represents
      N-methyl-D-glucamine. Additional species containing up to four antimony atoms and
      five N-methyl-D-glucamine moieties and corresponding to the general form (NMG
      Sb)n-NMG are also present. These results suggest that this agent is a complex
      mixture that exists in equilibrium in aqueous solution.

PMID- 9593131
TI  - Fosfomycin reduces CD15s-related antigen expression of Streptococcus pyogenes.
AB  - We have previously shown the immunological mimicry of human sialyl-Lewis(x)
      (CD15s) by a surface antigen of Streptococcus pyogenes. This mimicking surface
      antigen may act as a ligand to the selectin family and may induce antibody
      production against CD15s on host cells, suggesting a possible role in the
      pathogenesis of S. pyogenes. In this study, the effects of antibiotics on the
      CD15s-related antigen expression of S. pyogenes were examined at a concentration
      below the MIC (sub-MIC). The amounts of CD15s on the surfaces of S. pyogenes
      cells and on the surfaces of S. pyogenes biofilms were determined by a whole-cell
      enzyme-linked immunosorbent assay and by laser scanning fluorescence microscopy,
      respectively, by using an anti-CD15s monoclonal antibody. At the sub-MICs,
      fosfomycin (1R,2S-1,2-epoxypropyl phosphonic acid), its enantiomer (1S,2R-1,2
      epoxypropyl phosphonic acid), and benzylpenicillin significantly inhibited the
      CD15s expression of all strains studied. The effects of fosfomycin and its
      enantiomer on biofilms were also observed by scanning electron microscopy.
      Incubation of S. pyogenes with the sub-MIC of fosfomycin or its enantiomer, which
      has no antibacterial activity, reduced the amount of CD15s on the biofilm surface
      and made it smooth. These results suggest that fosfomycin or its enantiomer might
      be useful for preventing S. pyogenes adherence to human CD15s receptors and the
      resulting immunological pathogenicity.

PMID- 9593132
TI  - Characterization of vancomycin-resistant Enterococcus faecium isolates from the
      United States and their susceptibility in vitro to dalfopristin-quinupristin.
AB  - In the course of clinical studies with the investigational streptogramin
      antimicrobial dalfopristin-quinupristin, isolates of vancomycin-resistant
      Enterococcus faecium were referred to our laboratory from across the United
      States. Seventy-two percent of the strains were of the VanA type, phenotypically
      and genotypically, while 28% were of the VanB type. High-level resistance to
      streptomycin or gentamicin was observed in 86 and 81%, respectively, of the VanA
      strains but in only 69 and 66%, respectively, of the VanB strains. These
      enterococci were resistant to ampicillin (MIC for 50% of the isolates tested
      [MIC50] and MIC90, 128 and 256 microg/ml, respectively) and to the other approved
      agents tested, with the exception of chloramphenicol (MIC90, 8 microg/ml) and
      novobiocin (MIC90, 1 microg/ml). Considering all of the isolates submitted,
      dalfopristin-quinupristin inhibited 86.4% of them at concentrations of < or = 1
      microg/ml and 95.1% of them at < or = 2 microg/ml. However, for the data set
      comprised of only the first isolate submitted for each patient, 94.3% of the
      strains were inhibited at concentrations of < or = 1 microg/ml and 98.9% were
      inhibited at concentrations of < or = 2 microg/ml. Multiple drug resistance was
      very common among these isolates of vancomycin-resistant E. faecium, while
      dalfopristin-quinupristin inhibited the majority at concentrations that are
      likely to be clinically relevant.

PMID- 9593133
TI  - Comparison of concentrations of sulbactam-ampicillin administered by bolus
      injections or bolus plus continuous infusion in tissues of patients undergoing
      colorectal surgery.
AB  - The concentrations of sulbactam and ampicillin were determined in sera and
      different abdominal tissues of 16 patients who underwent elective colorectal
      surgery. Patients were randomly allocated to two groups. At the time of induction
      of anesthesia, patients in group 1 (eight patients) were given 1,000 mg of
      sulbactam with 2,000 mg of ampicillin by intravenous bolus injection (3 min).
      This dose was administered again after 2 h by bolus injection by the same route.
      Patients in group 2 (eight patients) were given the same initial dose of
      sulbactam-ampicillin by bolus injection (3 min). Then, a continuous infusion of
      1,000 mg of sulbactam with 2,000 mg of ampicillin in normal saline was
      immediately started and was administered over a 4-h period. Blood samples were
      collected to determine peak (10 min) and trough (end of surgery) antibiotic
      levels. Serial blood samples were also collected at predetermined periods (at the
      time of opening and closing of the abdominal cavity and at the time of surgical
      anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples
      were collected simultaneously. Antibiotic concentrations were determined by high
      performance liquid chromatography. Similar levels of the drugs in serum were
      observed for the two regimens of administration, with trough sulbactam levels of
      33 +/- 16 and 37 +/- 22 microg/ml in groups 1 and 2, respectively, and trough
      ampicillin levels of 72 +/- 55 and 79 +/- 47 microg/ml in groups 1 and 2,
      respectively. Similar sulbactam concentrations were observed in abdominal tissues
      whichever regimen of administration was used; in fatty tissues the sulbactam
      concentrations ranged from 2.7 to 3.8 microg/g for group 1 and from 1.7 to 4.0
      microg/g for group 2, and sulbactam concentrations in the colonic wall were 5.6
      +/- 7.7 and 6.8 +/- 3.2 microg/g in groups 1 and 2, respectively (not
      significant). Again, no influence of the regimen of administration was observed
      on tissue ampicillin concentrations; in fatty tissues ampicillin concentrations
      ranged from 4.1 to 5.4 microg/g for group 1 and from 3.2 to 5.8 microg/g for
      group 2, and sulbactam concentrations in the colonic wall were 7.0 +/- 2.8 and
      11.0 +/- 4.7 microg/g for groups 1 and 2, respectively (not significant). In most
      patients, the concentrations of ampicillin-sulbactam were greater than the MIC at
      which 50% of isolates are inhibited (MIC50) for Bacteroides fragilis in the fatty
      tissues. In the colonic wall, for most patients the concentrations of ampicillin
      sulbactam were greater than the MIC90 for B. fragilis. No influence of the
      regimen of administration was observed on the ratio of the two components in the
      tissues investigated and in sera. In conclusion, a second intraoperative bolus
      injection or a continuous infusion were equally effective in maintaining
      sulbactam-ampicillin concentrations in abdominal tissues. The first method of
      administration can be recommended since it is easier to handle.

PMID- 9593134
TI  - Levofloxacin population pharmacokinetics and creation of a demographic model for
      prediction of individual drug clearance in patients with serious community
      acquired infection.
AB  - Population pharmacokinetic modeling is a useful approach to obtaining estimates
      of both population and individual pharmacokinetic parameter values. The potential
      for relating pharmacokinetic parameters to pharmacodynamic outcome variables,
      such as efficacy and toxicity, exists. A logistic regression relationship between
      the probability of a successful clinical and microbiological outcome and the peak
      concentration-to-MIC ratio (and also the area under the plasma concentration-time
      curve [AUC]/MIC ratio) has previously been developed for levofloxacin; however,
      levofloxacin assays for determination of the concentration in plasma are not
      readily available. We attempted to derive and validate demographic variable
      models to allow prediction of the peak concentration in plasma and clearance (CL)
      from plasma for levofloxacin. Two hundred seventy-two patients received
      levofloxacin intravenously for the treatment of community-acquired infection of
      the respiratory tract, skin or soft tissue, or urinary tract, and concentrations
      in plasma, guided by optimal sampling theory, were obtained. Patient data were
      analyzed by the Non-Parametric Expectation Maximization approach. Maximum a
      posteriori probability Bayesian estimation was used to generate individual
      parameter values, including CL. Peak concentrations were simulated from these
      estimates. The first 172 patients were used to produce demographic models for the
      prediction of CL and the peak concentration. The remaining 100 patients served as
      the validation group for the model. A median bias and median precision were
      calculated. A two-compartment model was used for the population pharmacokinetic
      analysis. The mean CL and the mean volume of distribution of the central
      compartment (V1) were 9.27 liters/h and 0.836 liter/kg, respectively. The mean
      values for the intercompartmental rate constants, the rate constant from the
      central compartment to the peripheral compartment (Kcp) and the rate constant
      from the peripheral compartment to the central compartment (Kpc), were 0.487 and
      0.647 h(-1), respectively. The mean peak concentration and the mean AUC values
      normalized to a dosage of 500 mg every 24 h were 8.67 microg/ml and 72.53 microg
      x h/ml, respectively. The variables included in the final model for the
      prediction of CL were creatinine clearance (CLCR), race, and age. The median bias
      and median precision were 0.5 and 18.3%, respectively. Peak concentrations were
      predicted by using the demographic model-predicted parameters of CL, V1, Kcp and
      Kpc, in the simulation. The median bias and the median precision were 3.3 and
      21.8%, respectively. A population model of the disposition of levofloxacin has
      been developed. Population demographic models for the prediction of peak
      concentration and CL from plasma have also been successfully developed. However,
      the performance of the model for the prediction of peak concentration was likely
      insufficient to be of adequate clinical utility. The model for the prediction of
      CL was relatively robust, with acceptable bias and precision, and explained a
      reasonable amount of the variance in the CL of levofloxacin from plasma in the
      population (r2 = 0.396). Estimated CLCR, age, and race were the final model
      covariates, with CLCR explaining most of the population variance in the CL of
      levofloxacin from plasma. This model can potentially optimize the benefit derived
      from the pharmacodynamic relationships previously developed for levofloxacin.

PMID- 9593135
TI  - Pharmacodynamics of fluconazole in a murine model of systemic candidiasis.
AB  - In this study we defined the pharmacodynamic parameter that optimizes outcome in
      deep-seated Candida albicans infections treated with fluconazole. Using a murine
      model of systemic candidiasis, we conducted single-dose dose-ranging studies with
      fluconazole to determine the dosage of this drug that resulted in a 50% reduction
      in fungal densities (50% effective dose [ED50]) in kidneys versus the fungal
      densities in the kidneys of untreated controls. We found that the ED50 of
      fluconazole given intraperitoneally was 4.56 mg/kg of body weight/day (95%
      confidence interval, 3.60 to 5.53 mg/kg/day), and the dose-response relationship
      was best described by an inhibitory sigmoid maximal effect (Emax) curve. To
      define the pharmacodynamics of fluconazole, we gave dosages lower than,
      approximating, and higher than the ED50 of fluconazole (range, 3.5 to 5.5
      mg/kg/day, equivalent to the ED16 to the ED75) to various groups of infected
      animals using three dose-fractionation schedules. For each total dose of
      fluconazole examined, the dose-fractionation schedules optimized the ratio of the
      area under the concentration-time curve (AUC) to the MIC (the AUC/MIC ratio), the
      ratio of the maximum concentration of drug in serum (Cmax) to the MIC, and the
      time that the drug remained above the MIC for the infecting C. albicans isolate.
      Similar reductions in fungal densities in kidneys were seen between groups that
      received the same total dose of fluconazole in one, two, or four equally divided
      doses. Thus, dose-fractionation studies demonstrated that the pharmacodynamic
      parameter of fluconazole that best predicted outcome was the AUC/MIC ratio.

PMID- 9593136
TI  - Chromosomally encoded ampC-type beta-lactamase in a clinical isolate of Proteus
      mirabilis.
AB  - A clinical strain of Proteus mirabilis (CF09) isolated from urine specimens of a
      patient displayed resistance to amoxicillin (MIC >4,096 microg/ml), ticarcillin
      (4,096 microg/ml), cefoxitin (64 microg/ml), cefotaxime (256 microg/ml), and
      ceftazidime (128 microg/ml) and required an elevated MIC of aztreonam (4
      microg/ml). Clavulanic acid did not act synergistically with cephalosporins. Two
      beta-lactamases with apparent pIs of 5.6 and 9.0 were identified by isoelectric
      focusing on a gel. Substrate and inhibition profiles were characteristic of an
      AmpC-type beta-lactamase with a pI of 9.0. Amplification by PCR with primers for
      ampC genes (Escherichia coli, Enterobacter cloacae, and Citrobacter freundii) of
      a 756-bp DNA fragment from strain CF09 was obtained only with C. freundii
      specific primers. Hybridization results showed that the ampC gene is only
      chromosomally located while the TEM gene is plasmid located. After cloning of the
      gene, analysis of the complete nucleotide sequence (1,146 bp) showed that this
      ampC gene is close to blaCMY-2, from which it differs by three point mutations
      leading to amino acid substitutions Glu --> Gly at position 22, Trp --> Arg at
      position 201, and Ser --> Asn at position 343. AmpC beta-lactamases derived from
      that of C. freundii (LAT-1, LAT-2, BIL-1, and CMY-2) have been found in
      Klebsiella pneumoniae, E. coli, and Enterobacter aerogenes and have been reported
      to be plasmid borne. This is the first example of a chromosomally encoded AmpC
      type beta-lactamase observed in P. mirabilis. We suggest that it be designated
      CMY-3.

PMID- 9593137
TI  - Bactericidal activity of a single-dose combination of ofloxacin plus minocycline,
      with or without rifampin, against Mycobacterium leprae in mice and in lepromatous
      patients.
AB  - To develop a fully supervisable, monthly administered regimen for treatment of
      leprosy, the bactericidal effect of a single-dose combination of ofloxacin (OFLO)
      and minocycline (MINO), with or without rifampin (RMP), against Mycobacterium
      leprae was studied in the mouse footpad system and in previously untreated
      lepromatous leprosy patients. Bactericidal activity was measured by the
      proportional bactericidal method. In mouse experiments, the activity of a single
      dose of the combination OFLO-MINO was dosage related; the higher dosage of the
      combination displayed bactericidal activity which was significantly inferior to
      that of a single dose of RMP, whereas the lower dosage did not exhibit a
      bactericidal effect. In the clinical trial, 20 patients with previously untreated
      lepromatous leprosy were treated with a single dose consisting of either 600 mg
      of RMP plus 400 mg of OFLO and 100 mg of MINO or 400 mg of OFLO plus 100 mg of
      MINO. The OFLO-MINO combination exhibited definite bactericidal activity in 7 of
      10 patients but was less bactericidal than the RMP-OFLO-MINO combination. Both
      combinations were well tolerated. Because of these promising results, a test of
      the efficacy of multiple doses of ROM in a larger clinical trial appears
      justified.

PMID- 9593138
TI  - Isolation of nitrofurantoin-resistant mutants of nitroreductase-producing
      Clostridium sp. strains from the human intestinal tract.
AB  - Five spontaneous nitrofurantoin-resistant mutants (one each of Clostridium
      leptum, Clostridium paraputrificum, two other Clostridium spp. strains from the
      human intestinal microflora, and Clostridium perfringens ATCC 3626) were selected
      by growth on a nitrofurantoin-containing medium. All of the Clostridium wild-type
      and mutant strains produced nitroreductase, as was shown by the conversion of 4
      nitrobenzoic acid to 4-aminobenzoic acid. High-performance liquid chromatography
      (HPLC) analysis of the mutants during incubation with 50 microg of nitrofurantoin
      per ml showed the gradual disappearance of the nitrofurantoin peak. The
      nitrofurantoin peak also disappeared when cell-free supernatants instead of
      cultures of each of the resistant and wild-type bacteria were used, but it
      persisted if the cell-free supernatants had been inactivated by heat. At least
      two of the mutants converted nitrofurantoin to metabolites without antibacterial
      activity, as was shown by a bioassay with a nitrofurantoin-susceptible Bacillus
      sp. strain. Nitrofurantoin at a high concentration (50 microg/ml) continued to
      exert some toxicity, even on the resistant strains, as was evident from the
      longer lag phases. This study indicates that Clostridium strains can develop
      resistance to nitrofurantoin while retaining the ability to produce
      nitroreductase; the mutants metabolized nitrofurantoin to compounds without
      antibacterial activity.

PMID- 9593139
TI  - Activities of HMR 3004 (RU 64004) and HMR 3647 (RU 66647) compared to those of
      erythromycin, azithromycin, clarithromycin, roxithromycin, and eight other
      antimicrobial agents against unusual aerobic and anaerobic human and animal bite
      pathogens isolated from skin and soft tissue infections in humans.
AB  - The activities of HMR 3004 and HMR 3647 and comparator agents, especially
      macrolides, were determined by the agar dilution method against 262 aerobic and
      120 anaerobic strains isolated from skin and soft tissue infections associated
      with human and animal bite wounds. HMR 3004 and HMR 3647 were active against
      almost all aerobic and fastidious facultative isolates (MIC at which 90% of the
      isolates are inhibited [MIC90], < or = 0.5 and 1 microg/ml, respectively) and
      against all anaerobes [Bacteroides tectum, Porphyromonas macacae (salivosa),
      Prevotella heparinolytica, Porphyromonas sp., Prevotella sp., and
      peptostreptococci] at < or = 0.25 and < or = 0.5 microg/ml, respectively, except
      Fusobacterium nucleatum (HMR 3004, MIC90 = 16 microg/ml; HMR 3647, MIC90 = 8
      microg/ml) and other Fusobacterium species (MIC90, 1 and 2 microg/ml,
      respectively). In general, HMR 3004 and HMR 3647 were more active than any of the
      macrolides tested. Azithromycin was more active than clarithromycin against all
      Pasteurella species, including Pasteurella multocida subsp. multocida, Eikenella
      corrodens, and Fusobacterium species, while clarithromycin was more active than
      azithromycin against Corynebacterium species, Weeksella zoohelcum, B. tectum, and
      P. heparinolytica.

PMID- 9593140
TI  - CNI-H0294, a nuclear importation inhibitor of the human immunodeficiency virus
      type 1 genome, abrogates virus replication in infected activated peripheral blood
      mononuclear cells.
AB  - Active nuclear importation of the human immunodeficiency virus (HIV) type 1 (HIV
      1) preintegration complex (PIC) is required for the productive infection of
      nondividing cells, but it is believed to be dispensable for the infection of
      proliferating cells, such as activated T lymphocytes. To investigate this
      question, we exploited the properties of the small arylene bis (methyl ketone)
      compound CNI-H0294. We have previously shown that this compound associated with
      the HIV-1 matrix protein nuclear localization sequence and blocked binding of the
      HIV-1 PIC to yeast karyopherin alpha. CNI-H0294 abrogated nuclear importation of
      the HIV-1 genome in macrophages and effectively inhibited infection of
      nondividing cells. In this study we demonstrate that CNI-H0294 inhibits binding
      of the HIV-1 PIC to human karyopherin alpha and reduces nuclear importation of
      the viral genome in primary peripheral blood mononuclear cells (PBMCs). We also
      demonstrate that CNI-H0294 inhibits acute infection of PBMC cultures in vitro
      with a primary isolate of HIV-1 and reduces virus replication and virus load in
      cultures of endogenously infected PBMCs from seropositive individuals. Thus, as
      for infection of nondividing, terminally differentiated macrophages, HIV-1 uses
      active nuclear importation of the virus genome to infect activated CD4+ T cells.
      These results support nuclear importation as a novel target and CNI-H0294 and its
      derivatives as novel compounds for therapeutic intervention in HIV infection and
      AIDS.

PMID- 9593141
TI  - Sorivudine versus acyclovir for treatment of dermatomal herpes zoster in human
      immunodeficiency virus-infected patients: results from a randomized, controlled
      clinical trial. Collaborative Antiviral Study Group/AIDS Clinical Trials Group,
      Herpes Zoster Study Group.
AB  - The present randomized, double-blind, placebo-controlled, multicenter clinical
      trial was designed to compare the efficacy and tolerability of sorivudine [1-beta
      D-arabinofuranosyl-E-(2-bromovinyl)uracil] and acyclovir for the treatment of
      dermatomal herpes zoster in human immunodeficiency virus (HIV)-seropositive
      patients. A total of 170 HIV-seropositive adults presenting with herpes zoster
      (confirmed by direct fluorescent-antigen testing and/or viral culture) were
      enrolled and randomized to receive a 10-day course of orally administered
      sorivudine (40 mg once daily plus acyclovir placebos) or acyclovir (800 mg five
      times daily plus sorivudine placebo). Patients were monitored daily to document
      the events of cutaneous healing, pain, zoster-related complications, and drug
      related adverse events. Patients were reassessed on days 21 and 28 and then once
      monthly for 1 year. The primary efficacy endpoint was time to the cessation of
      new vesicle formation. Secondary efficacy endpoints included times to other
      events of cutaneous healing, resolution of pain, and frequency of dissemination
      and zoster recurrence. In a multivariate analysis, sorivudine was superior to
      acyclovir for reducing the times to the cessation of new vesicle formation
      (relative risk [RR] = 1.54, 95% confidence interval [CI] = 1.00 to 2.36; P =
      0.049) and total lesion crusting (RR = 1.48, 95% CI = 1.07 to 2.04; P = 0.017).
      In a univariate analysis, there was a trend favoring sorivudine for the cessation
      of new vesicle formation (median of 3 versus 4 days; P = 0.07) and a significant
      advantage for time to total lesion crusting (median of 7 versus 8 days; P =
      0.02). The time to the resolution of zoster-associated pain, the frequency of
      dissemination, and the frequency of zoster recurrence were not different between
      the two treatment groups. Both drugs were well tolerated. Sorivudine is an
      effective drug for the treatment of herpes zoster in HIV-infected patients and
      results in accelerated cutaneous healing when compared with acyclovir therapy.

PMID- 9593142
TI  - Disposition of the acyclic nucleoside phosphonate (S)-9-(3-hydroxy-2
      phosphonylmethoxypropyl)adenine.
AB  - The acyclic nucleoside phosphonate (S)-9-(3-hydroxy-2
      phosphonylmethoxypropyl)adenine [(S)-HPMPA] has been shown to be active against
      pathogens, like hepatitis B viruses and Plasmodium parasites, that infect
      parenchymal liver cells. (S)-HPMPA is therefore an interesting candidate drug for
      the treatment of these infections. To establish effective therapeutic protocols
      for (S)-HPMPA, it is essential that the kinetics of its hepatic uptake be
      evaluated and that the role of the various liver cell types be examined. In the
      present study, we investigated the disposition of (S)-HPMPA and assessed its
      hepatic uptake. Rats were intravenously injected with [3H](S)-HPMPA, and after an
      initial rapid distribution phase (360 +/- 53 ml/kg of body weight), the
      radioactivity was cleared from the circulation with a half-life of 11.7 +/- 1.4
      min. The tissue distribution of [3H](S)-HPMPA was determined at 90 min after
      injection (when >99% of the dose cleared). Most (57.0% +/- 1.1%) of the injected
      [3H](S)-HPMPA was excreted unchanged in the urine. The radioactivity that was
      retained in the body was almost completely recovered in the kidneys and the liver
      (68.4% +/- 2.5% and 16.1% +/- 0.4% of the radioactivity in the body,
      respectively). The uptake of [3H](S)-HPMPA by the liver occurred mainly by
      parenchymal cells (92.1% +/- 3.4% of total uptake by the liver). Kupffer cells
      and endothelial cells accounted for only 6.1% +/- 3.5% and 1.8% +/- 0.8% of the
      total uptake by the liver, respectively. Preinjection with probenecid reduced the
      hepatic and renal uptake of [3H](S)-HPMPA by approximately 75%, which points to a
      major role of a probenecid-sensitive transporter in the uptake of (S)-HPMPA by
      both tissues. In conclusion, we show that inside the liver, (S)-HPMPA is mainly
      taken up by parenchymal liver cells. However, the level of uptake by the kidneys
      is much higher, which leads to nephrotoxicity. An approach in which (S)-HPMPA is
      coupled to carriers that are specifically taken up by parenchymal cells may
      increase the effectiveness of the drug in the liver and reduce its renal
      toxicity.

PMID- 9593143
TI  - Defluorinated sparfloxacin as a new photoproduct identified by liquid
      chromatography coupled with UV detection and tandem mass spectrometry.
AB  - Photodegradation of sparfloxacin was observed by means of high-pressure liquid
      chromatography with UV detection and liquid chromatography coupled with UV
      detection and tandem mass spectrometry (LC-MS/MS). Three products were detected.
      Comparison with an independently synthesized derivative of sparfloxacin revealed
      the structure of one product which is believed to be 8-desfluorosparfloxacin. The
      second product is likely to be formed by the splitting off of a fluorine and a
      cyclopropyl ring. Thus, photodefluorination of quinolone antibacterial agents is
      found and proved for the first time by LC-MS/MS.

PMID- 9593144
TI  - Sequencing, disruption, and characterization of the Candida albicans sterol
      methyltransferase (ERG6) gene: drug susceptibility studies in erg6 mutants.
AB  - The rise in the frequency of fungal infections and the increased resistance noted
      to the widely employed azole antifungals make the development of new antifungals
      imperative for human health. The sterol biosynthetic pathway has been exploited
      for the development of several antifungal agents (allylamines, morpholines,
      azoles), but additional potential sites for antifungal agent development are yet
      to be fully investigated. The sterol methyltransferase gene (ERG6) catalyzes a
      biosynthetic step not found in humans and has been shown to result in several
      compromised phenotypes, most notably markedly increased permeability, when
      disrupted in Saccharomyces cerevisiae. The Candida albicans ERG6 gene was
      isolated by complementation of a S. cerevisiae erg6 mutant by using a C. albicans
      genomic library. Sequencing of the Candida ERG6 gene revealed high homology with
      the Saccharomyces version of ERG6. The first copy of the Candida ERG6 gene was
      disrupted by transforming with the URA3 blaster system, and the second copy was
      disrupted by both URA3 blaster transformation and mitotic recombination. The
      resulting erg6 strains were shown to be hypersusceptible to a number of sterol
      synthesis and metabolic inhibitors, including terbinafine, tridemorph,
      fenpropiomorph, fluphenazine, cycloheximide, cerulenin, and brefeldin A. No
      increase in susceptibility to azoles was noted. Inhibitors of the ERG6 gene
      product would make the cell increasingly susceptible to antifungal agents as well
      as to new agents which normally would be excluded and would allow for clinical
      treatment at lower dosages. In addition, the availability of ERG6 would allow for
      its use as a screen for new antifungals targeted specifically to the sterol
      methyltransferase.

PMID- 9593145
TI  - Interactions of beta-lactamases with sanfetrinem (GV 104326) compared to those
      with imipenem and with oral beta-lactams.
AB  - Sanfetrinem is a trinem beta-lactam which can be administered orally as a hexatil
      ester. We examined whether its beta-lactamase interactions resembled those of the
      available carbapenems, i.e., stable to AmpC and extended-spectrum beta-lactamases
      but labile to class B and functional group 2f enzymes. The comparator drugs were
      imipenem, oral cephalosporins, and amoxicillin. MICs were determined for beta
      lactamase expression variants, and hydrolysis was examined directly with
      representative enzymes. Sanfetrinem was a weak inducer of AmpC beta-lactamases
      below the MIC and had slight lability, with a kcat of 0.00033 s(-1) for the
      Enterobacter cloacae enzyme. Its MICs for AmpC-derepressed E. cloacae and
      Citrobacter freundii were 4 to 8 microg/ml, compared with MICs of 0.12 to 2
      microg/ml for AmpC-inducible and -basal strains; MICs for AmpC-derepressed
      Serratia marcescens and Morganella morganii were not raised. Cefixime and
      cefpodoxime were more labile than sanfetrinem to the E. cloacae AmpC enzyme, and
      AmpC-derepressed mutants showed much greater resistance; imipenem was more stable
      and retained full activity against derepressed mutants. Like imipenem,
      sanfetrinem was stable to TEM-1 and TEM-10 enzymes and retained full activity
      against isolates and transconjugants with various extended-spectrum TEM and SHV
      enzymes, whereas these organisms were resistant to cefixime and cefpodoxime.
      Sanfetrinem, like imipenem and cefixime but unlike cefpodoxime, also retained
      activity against Proteus vulgaris and Klebsiella oxytoca strains that
      hyperproduced potent chromosomal class A beta-lactamases. Functional group 2f
      enzymes, including Sme-1, NMC-A, and an unnamed enzyme from Acinetobacter spp.,
      increased the sanfetrinem MICs by up to 64-fold. These enzymes also compromised
      the activities of imipenem and amoxicillin but not those of the cephalosporins.
      The hydrolysis of sanfetrinem was examined with a purified Sme-1 enzyme, and
      biphasic kinetics were found. Finally, zinc beta-lactamases, including IMP-1 and
      the L1 enzyme of Stenotrophomonas maltophilia, conferred resistance to
      sanfetrinem and all other beta-lactams tested, and hydrolysis was confirmed with
      the IMP-1 enzyme. We conclude that sanfetrinem has beta-lactamase interactions
      similar to those of the available carbapenems except that it is a weaker inducer
      of AmpC types, with some tendency to select derepressed mutants, unlike imipenem
      and meropenem.

PMID- 9593146
TI  - Steady-state pharmacokinetics and electrocardiographic pharmacodynamics of
      clarithromycin and loratadine after individual or concomitant administration.
AB  - To evaluate the potential for an interaction between clarithromycin and
      loratadine, healthy male volunteers (n = 24) received each of the following
      regimens according to a randomized crossover design: 500 mg of clarithromycin
      orally every 12 h (q12h) for 10 days, 10 mg of loratadine orally q24h for 10
      days, and the combination of clarithromycin and loratadine. A washout interval of
      14 days separated regimens. The addition of loratadine did not statistically
      significantly affect the steady-state pharmacokinetics of clarithromycin or its
      active metabolite, 14(R)-hydroxy-clarithromycin. However, the addition of
      clarithromycin statistically significantly altered the steady-state maximum
      observed plasma concentration and the area under the plasma concentration-time
      curve over a dosing interval for loratadine (+36 and +76%, respectively) and for
      descarboethoxyloratadine (DCL), the active metabolite of loratadine (+69 and
      +49%, respectively). Clarithromycin probably inhibits the oxidative metabolism of
      loratadine and DCL by the cytochrome P-450 3A subfamily. Electrocardiograms (n =
      12) were obtained over 24-h periods at baseline and steady state (day 10). The
      mean maximum QTc interval and area under the QTc interval-time curve on day 10
      were modestly increased (<3%) from baseline for all three regimens, but no QTc
      interval exceeded 439 ms for any subject. Elevated steady-state concentrations of
      loratadine and DCL do not appear to be associated with adverse cardiovascular
      effects related to prolongation of the QTc interval. Loratadine and
      clarithromycin were well tolerated, alone and in combination.

PMID- 9593149
TI  - Flow cytometric assessment of the postantibiotic effect of methicillin on
      Staphylococcus aureus.
AB  - The postantibiotic effect (PAE) following a 2-h exposure of Staphylococcus aureus
      NCTC 6571 to methicillin (5x the MIC) was investigated with fluorescent probes, 5
      cyano-2,3-di-4-tolyl tetrazolium chloride (CTC), an indicator of respiratory
      activity, and the membrane potential-sensitive compound bis-(1,3
      dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)]. Counts of the numbers of
      CFU on solid agar correlated well with information gained from the CTC and
      DiBAC4(3) fluorescence intensity distributions obtained by flow cytometry and
      revealed that the postantibiotic effect was 3.1 h. Due to the capacity of flow
      cytometry to provide information on the heterogeneity of a bacterial population,
      both fluorescent probes identified the emergence of an active subpopulation 4 h
      after removal of the methicillin, indicating the recovery of a small percentage
      of the population. After removal of the methicillin and resuspension of the cells
      in methicillin-free medium, a further decrease in the respiratory activity and
      the membrane integrity of the population was observed, although the CFU counts
      hardly varied, indicating continued antibiotic-induced damage. Also, CTC
      fluorescence measurements identified numerous subpopulations during the PAE
      period; this suggests that the PAE is complex, with individual organisms
      exhibiting various degrees of recovery. Flow cytometry thus provides a rapid and
      sensitive alternative to traditional techniques that have been used to study PAE,
      with the added advantage that physiological changes can be detected as they
      arise.

PMID- 9593147
TI  - Cloning and sequencing of the gene encoding Toho-2, a class A beta-lactamase
      preferentially inhibited by tazobactam.
AB  - Escherichia coli TUM1083, which is resistant to ampicillin, carbenicillin,
      cephaloridine, cephalothin, piperacillin, cefuzonam, and aztreonam while being
      sensitive to cefoxitin, moxalactam, cefmetazole, ceftazidime, and imipenem, was
      isolated from the urine of a patient treated with beta-lactam antibiotics. The
      beta-lactamase (Toho-2) purified from the bacteria hydrolyzed beta-lactam
      antibiotics such as penicillin G, carbenicillin, cephaloridine, cefoxitin,
      cefotaxime, ceftazidime, and aztreonam and especially had increased relative
      hydrolysis rates for cephalothin, cephaloridine, cefotaxime, and ceftizoxime.
      Different from other extended-spectrum beta-lactamases, Toho-2 was inhibited 16
      fold better by the beta-lactamase inhibitor tazobactam than by clavulanic acid.
      Resistance to beta-lactams was transferred by conjugation from E. coli TUM1083 to
      E. coli ML4909, and the transferred plasmid was about 54.4 kbp, belonging to the
      incompatibility group IncFII. The cefotaxime resistance gene for Toho-2 was
      subcloned from the 54.4-kbp plasmid. The sequence of the gene was determined, and
      the open reading frame of the gene was found to consist of 981 bases. The
      nucleotide sequence of the gene (DDBJ accession no. D89862) designated as
      bla(toho) was found to have 76.3% identity to class A beta-lactamase CTX-M-2 and
      76.2% identity to Toho-1. It has 55.9% identity to SHV-1 beta-lactamase and 47.5%
      identity to TEM-1 beta-lactamase. Therefore, the newly isolated beta-lactamase
      designated as Toho-2 produced by E. coli TUM1083 is categorized as an enzyme
      similar to Toho-1 group beta-lactamases rather than to mutants of TEM or SHV
      enzymes. According to the amino acid sequence deduced from the DNA sequence, the
      precursor consisted of 327 amino acid residues. Comparison of Toho-2 with other
      beta-lactamase (non-Toho-1 group) suggests that the substitutions of threonine
      for Arg-244 and arginine for Asn-276 are important for the extension of the
      substrate specificity.

PMID- 9593148
TI  - Photoaffinity analog of the semisynthetic echinocandin LY303366: identification
      of echinocandin targets in Candida albicans.
AB  - The echinocandins are a family of cyclic lipopeptides with potent antifungal
      activity. These compounds inhibit the synthesis of BETA-1,3-glucan in fungi. The
      new semisynthetic echinocandin LY303366 was derivatized to produce a
      photoactivatable cross-linking echinocandin analog with antifungal activity. This
      analog was radioiodinated and used as a probe in microsomal membrane preparations
      of Candida albicans which contain glucan synthase activity. The photoaffinity
      probe identified two major proteins of 40 and 18 kDa in both membrane
      preparations. Labeling of these proteins was specific in that it required
      irradiation with UV light and was effectively competed against with unlabeled
      echinocandin analogs. In addition, the abilities of echinocandin analogs to
      compete with the photoaffinity probe correlated to their relative antifungal
      potencies and glucan synthase inhibition. The 40-kDa protein was isolated, and
      partial sequences were obtained from internal peptide fragments of the protein.
      Analysis of the sequences of these internal peptides of the 40-kDa protein
      revealed that it was a new protein not previously described as being involved in
      glucan synthesis or the mode of action of echinocandins.

PMID- 9593150
TI  - Novel inhibitory effects of gamma-glutamylcysteine ethyl ester against human
      immunodeficiency virus type 1 production and propagation.
AB  - The anti-human immunodeficiency virus type I (anti-HIV-1) effects of gamma
      glutamylcysteine ethyl ester (gamma-GCE; TEI-2306) were examined in vitro. In
      initial studies using a vigorously HIV-1-producing human T-lymphocytic cell line,
      gamma-GCE displayed a novel biphasic repressive effect on chronic HIV-1 infection
      that was unlike that of other glutathione prodrugs or other reported
      antioxidants. In high doses, up to a concentration of 2.5 mM, at which neither
      glutathione (GSH) nor another GSH precursor has shown inhibitory effects, gamma
      GCE potently inhibited the production of HIV-1 by a selective cytopathic effect
      against infected cells, while the viability and growth of uninfected cells were
      unaffected at the same gamma-GCE concentrations. At lower concentrations (200 to
      400 microM), gamma-GCE significantly repressed the virus production from
      chronically HIV-1-expressing cells without affecting their viability. The
      discrepancy of the thresholds of the toxic doses between infected and uninfected
      cells was found to be more than 10-fold. Relatively high doses of gamma-GCE,
      utilized in acute HIV-1 infection of T-lymphocytic cells, entirely blocked the
      propagation of HIV-1 and rescued the cells from HIV-1-induced cell death.
      Furthermore, gamma-GCE at such concentrations was found to directly inhibit the
      infectivity of HIV-1 within 4 h. Repressive effects of gamma-GCE on acute HIV-1
      infection in human primary human peripheral blood mononuclear cells were also
      demonstrated. Here, the anti-HIV-1 strategy utilizing gamma-GCE is removal of
      both HIV-1-producing cells and free infectious HIV-1 in vitro, in place of
      specific immunoclearance in vivo, which might lead to an arrest or slowing of
      viral propagation in HIV-1-infected individuals.

PMID- 9593151
TI  - Influence of test conditions on antifungal time-kill curve results: proposal for
      standardized methods.
AB  - This study was designed to examine the effects of antifungal carryover,
      agitation, and starting inoculum on the results of time-kill tests conducted with
      various Candida species. Two isolates each of Candida albicans, Candida
      tropicalis, and Candida glabrata were utilized. Test antifungal agents included
      fluconazole, amphotericin B, and LY303366. Time-kill tests were conducted in RPMI
      1640 medium buffered with morpholinepropanesulfonic acid (MOPS) to a pH of 7.0
      and incubated at 35 degrees C. Prior to testing, the existence of antifungal
      carryover was evaluated at antifungal concentrations ranging from 1x to 16x MIC
      by four plating methods: direct plating of 10, 30, and 100 microl of test
      suspension and filtration of 30 microl of test suspension through a 0.45-microm
      pore-size filter. Time-kill curves were performed with each isolate at drug
      concentrations equal to 2 x MIC, using a starting inoculum of approximately 10(5)
      CFU/ml, and incubated with or without agitation. Last, inoculum experiments were
      conducted over three ranges of starting inocula: 5 x 10(2) to 1 x 10(4), >1 x
      10(4) to 1 x 10(6), and >1 x 10(6) to 1 x 10(8) CFU/ml. Significant antifungal
      carryover (>25% reduction in CFU/milliliter from the control value) was observed
      with amphotericin B and fluconazole; however, carryover was eliminated with
      filtration. Agitation did not appreciably affect results. The starting inoculum
      did not significantly affect the activity of fluconazole or amphotericin B;
      however, the activity of LY303366 may be influenced by the starting inoculum.
      Before antifungal time-kill curve methods are routinely employed by
      investigators, methodology should be scrutinized and standardized procedures
      should be developed.

PMID- 9593152
TI  - In vitro antimicrobial activity of MSI-78, a magainin analog.
AB  - MSI-78 is a cationic peptide with broad-spectrum antimicrobial activity and is
      being developed as a topical agent. We compared the in vitro activity of MSI-78
      with those of ofloxacin and other antibiotics against fresh clinical isolates.
      Based on MIC distribution statistics, strains for which the MSI-78 MIC was < or =
      64 micro/ml were assumed to be susceptible for purposes of this report. Of 411
      aerobic isolates tested, 91% were susceptible to MSI-78, compared to 91% for
      ofloxacin and 92% for ciprofloxacin. Only enterococci consistently required > or
      = 64 microg of MSI-78/ml for inhibition. MSI-78 demonstrated bactericidal
      activity equivalent to that of ofloxacin. Of 61 anaerobes, 97% were susceptible
      to MSI-78. Of 10 isolates of Candida albicans, 3 were inhibited by MSI-78 at 24
      h. Further studies of this compound appear to be warranted.

PMID- 9593153
TI  - Pharmacokinetics of a new carbapenem, DA-1131, after intravenous administration
      to rats with uranyl nitrate-induced acute renal failure.
AB  - Because the physiological changes that occur in patients with acute renal failure
      could alter the pharmacokinetics of the drugs used to treat the disease, the
      pharmacokinetics of DA-1131, a new carbapenem antibiotic, were investigated after
      1-min intravenous administration of the drug (50 mg/kg of body weight) to control
      rats and rats with uranyl nitrate-induced acute renal failure (U-ARF rats). The
      impaired kidney function was observed in U-ARF rats on the basis of physiological
      parameters observed by microscopy of the kidney and obtained by chemical analysis
      of the plasma. After a 1-min intravenous infusion of DA-1131, the concentrations
      in plasma and the total area under the plasma concentration-time curve from time
      zero to time infinity increased significantly in U-ARF rats compared with those
      in control rats (13,000 versus 4,400 microg x min/ml). This was due to the
      significantly slower total body clearance (CL) of DA-1131 (3.84 versus 11.4
      ml/min/kg) from U-ARF rats than from control rats. The significantly slower CL of
      DA-1131 from U-ARF rats was due to both significantly slower renal clearance
      (0.000635 versus 4.95 ml/min/kg because of a significant decrease in the 8-h
      urinary excretion of unchanged DA-1131 [1.54 versus 43.8% of the intravenous
      dose] due to impaired kidney function, as proved by the significant decrease in
      creatinine clearance [0.0159 versus 4.29 ml/min/kg]) and significantly slower
      nonrenal clearance (3.80 versus 6.34 ml/min/kg because of a significant decrease
      in the metabolism of DA-1131 in the kidney) in U-ARF rats. The amounts of DA-1131
      recovered from all tissues studied (except the kidneys) were significantly higher
      for U-ARF rats than for control rats; however, the ratios of the amount in tissue
      to the concentration in plasma (except those for the kidney, small intestine, and
      spleen) were not significantly different between the two groups of rats,
      indicating that the affinity of DA-1131 for rat tissues was not changed
      considerably in U-ARF rats.

PMID- 9593154
TI  - Risk of development of in vitro resistance to amoxicillin, clarithromycin, and
      metronidazole in Helicobacter pylori.
AB  - We have studied initial killing, morphological alterations, the frequency of
      occurrence, and the selective growth of resistant subpopulations of Helicobacter
      pylori during exposure to amoxicillin, clarithromycin, or metronidazole by
      bioluminescence assay of intracellular ATP levels, microscopy, and a viable count
      assay. We found an induction of spheroplasts and a decrease in intracellular ATP
      levels after 21 h of exposure to high concentrations of amoxicillin. During
      clarithromycin exposure the onset of a decrease in intracellular ATP levels
      started after prolonged incubation, and with the highest concentration of
      clarithromycin an induction of coccoid forms was seen after 68 h. Metronidazole
      exposure resulted in the strongest initial decrease in intracellular ATP levels,
      and coccoid forms were seen after 21 h of exposure to high concentrations of
      metronidazole. Amoxicillin caused a low-level increase in resistant
      subpopulations, which indicates a need for surveillance of the amoxicillin
      susceptibility of H. pylori in order to detect decreasing susceptibility. No
      increase in the numbers of resistant subpopulations was demonstrated during
      clarithromycin exposure. Metronidazole selected resistant subpopulations, which
      caused high-level resistance in H. pylori.

PMID- 9593155
TI  - A new high-level gentamicin resistance gene, aph(2'')-Id, in Enterococcus spp.
AB  - Enterococcus casseliflavus UC73 is a clinical blood isolate with high-level
      resistance to gentamicin. DNA preparations from UC73 failed to hybridize with
      intragenic probes for aac(6')-Ie-aph(2'')-Ia and aph(2'')-Ic. A 4-kb fragment
      from UC73 was cloned and found to confer resistance to gentamicin in Escherichia
      coli DH5alpha transformants. Nucleotide sequence analysis revealed the presence
      of a 906-bp open reading frame whose deduced amino acid sequence had a region
      with homology to the aminoglycoside-modifying enzyme APH(2'')-Ic and to the C
      terminal domain of the bifunctional enzyme AAC(6')-APH(2''). The gene is
      designated aph(2'')-Id, and its observed phosphotransferase activity is
      designated APH(2'')-Id. A PCR-generated intragenic probe hybridized to the
      genomic DNA from 17 of 118 enterococcal clinical isolates (108 with high-level
      gentamicin resistance) from five hospitals. All 17 were vancomycin-resistant
      Enterococcus faecium isolates, and pulsed-field typing revealed three distinct
      clones. The combination of ampicillin plus either amikacin or neomycin exhibited
      synergistic killing against E. casseliflavus UC73. Screening and interpretation
      of high-level aminoglycoside resistance in enterococci may need to be modified to
      include detection of APH(2'')-Id.

PMID- 9593156
TI  - Meropenem versus cefuroxime plus gentamicin for treatment of serious infections
      in elderly patients.
AB  - In this multicenter study, the efficacy of and tolerability for meropenem were
      compared with those for the combination of cefuroxime-gentamicin (+/-
      metronidazole) for the treatment of serious bacterial infections in patients > or
      = 65 years of age. A total of 79 patients were randomized; thirty-nine received
      meropenem (1 g/8 h), and 40 received cefuroxime (1.5 g/8 h) plus gentamicin (4
      mg/kg of body weight daily) for 5 to 10 days. Metronidazole (500 mg/6 h) could be
      added to the cefuroxime-gentamicin regimen for the treatment of intra-abdominal
      infections (n = 10). Seventy patients were evaluable for clinical efficacy; the
      primary diagnoses were as follows: pneumonia in 41 patients (20 treated with
      meropenem, 21 treated with cefuroxime-gentamicin), intra-abdominal infection in
      10 patients (7 meropenem, 3 cefuroxime-gentamicin-metronidazole), urinary tract
      infection (UTI) in 11 patients (6 meropenem, 5 cefuroxime-gentamicin), sepsis
      syndrome in 7 patients (4 meropenem, 3 cefuroxime-gentamicin), and "other" in 1
      patient (cefuroxime-gentamicin). The pathogens isolated from 18 patients with
      bacteremia were as follows: Staphylococcus spp. (n = 2), Streptococcus spp. (n =
      2), members of the family Enterobacteriaceae (n = 11), and Bacteroides spp. (n =
      3). A satisfactory clinical response at the end of therapy was achieved in 26 of
      37 (70%) and 24 of 33 (73%) evaluable patients treated with meropenem and
      combination therapy, respectively. Clinical success was achieved in 23 of 31
      (74%) and 21 of 28 (75%) evaluable patients with infections other than UTIs,
      respectively. A satisfactory microbiological response occurred in 15 of 22 (68%)
      patients in the meropenem group compared with 12 of 19 (63%) treated with
      combination therapy. Renal failure occurred during therapy in 2 of 39 (5%)
      meropenem recipients compared with 5 of 40 (13%) of those treated with
      combination therapy. The findings in this small study indicate that meropenem is
      as efficacious for and as well tolerated by elderly patients as the combination
      of cefuroxime-gentamicin (+/- metronidazole).

PMID- 9593157
TI  - Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from
      compounds in human breast milk.
AB  - The development of new methods for prevention of sexually transmitted Chlamydia
      trachomatis infection is a top public health priority. Topical self-administered
      vaginal microbicides represent one such approach in which the organism is
      eradicated at the time of initial exposure. To this end, we examined the activity
      of five synthetic lipids adapted from naturally occurring compounds found in
      human breast milk. C. trachomatis serovar D or F elementary bodies were added to
      serial dilutions of the lipids and incubated for various times. Aliquots were
      then cultured in monolayers of McCoy cells, and inclusions were counted. A 7.5 mM
      concentration of 2-O-octyl-sn-glycerol completely prevented growth of C.
      trachomatis after 120 min of contact with the organism. The remaining lipids, 1-O
      octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity.
      On electron microscopic examination, the lipids were shown to have disrupted the
      chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the
      cell. Lipid activity was unaffected by the presence of 10% human blood or
      alterations in pH from 4.0 to 8.0, conditions reflecting those sometimes found in
      the vagina. Our results suggest that these lipids, especially 2-O-octyl-sn
      glycerol, may be effective as topical microbicides in preventing the transmission
      of C. trachomatis. Further efficacy and toxicity studies with these lipids and
      assessment of their activity against other sexually transmitted disease pathogens
      are in progress.

PMID- 9593158
TI  - Molecular heterogeneity of the L-1 metallo-beta-lactamase family from
      Stenotrophomonas maltophilia.
AB  - We have determined the nucleotide sequence of the blaS gene encoding the
      carbapenem-hydrolyzing L-1 beta-lactamase from Stenotrophomonas maltophilia
      GN12873. Analysis of the DNA and deduced amino acid sequences identified a
      product of 290 amino acids. Comparisons of the L-1 amino acid sequence with those
      of other zinc beta-lactamases showed 88.6% identity with the L-1 enzyme from S.
      maltophilia IID1275 and less than 20% identity with other class B metalloenzymes.

PMID- 9593159
TI  - Characterization of grlA, grlB, gyrA, and gyrB mutations in 116 unrelated
      isolates of Staphylococcus aureus and effects of mutations on ciprofloxacin MIC.
AB  - One hundred sixteen unrelated clinical isolates of Staphylococcus aureus (70
      ciprofloxacin resistant and 46 ciprofloxacin susceptible) from eight countries
      were studied for the presence of mutations in the grlA, grlB, gyrA, and gyrB gene
      loci. Two mutations within grlA (located at codons 80 and 84) and two mutations
      within gyrA (located at codons 84 and 88) were clearly associated with
      ciprofloxacin resistance, although other mutations detected within the four genes
      studied may also contribute to decreased susceptibility.

PMID- 9593160
TI  - Postantibiotic effect and postantibiotic sub-MIC effect of levofloxacin compared
      to those of ofloxacin, ciprofloxacin, erythromycin, azithromycin, and
      clarithromycin against 20 pneumococci.
AB  - The postantibiotic effect (PAE) (10 times the MIC of quinolones, 5 times the MIC
      of macrolides) and postantibiotic sub-MIC effect (PAE-SME) at 0.125, 0.25, and
      0.5 times the MIC were determined for levofloxacin, ciprofloxacin, ofloxacin,
      erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Quinolone
      PAEs ranged between 0.5 and 6.5 h, and macrolide PAEs ranged between 1 and 6 h.
      Measurable PAE-SMEs (in hours) at the three concentrations were 1 to 5, 1 to 8,
      and 1 to 8, respectively, for quinolones and 1 to 8, 1 to 8, and 1 to 6,
      respectively, for macrolides.

PMID- 9593161
TI  - Assessment of the effects of combination therapy with ciprofloxacin and fenbufen
      on the central nervous systems of healthy volunteers by quantitative
      electroencephalography.
AB  - The potential effects of concurrent administration of fenbufen and ciprofloxacin
      on central nervous system activity in healthy young subjects were investigated by
      electroencephalography (EEG). Visual analog scales (VAS) were used to assess
      subjective measures of concentration, vigilance, tension, and irritability. When
      ciprofloxacin was administered in combination with fenbufen, none of the EEG
      parameters or VAS ratings measured were significantly different from those
      measured when the drugs were administered alone.

PMID- 9593162
TI  - Sequence of the gene encoding a plasmid-mediated cefotaxime-hydrolyzing class A
      beta-lactamase (CTX-M-4): involvement of serine 237 in cephalosporin hydrolysis.
AB  - The sequence of the gene encoding a novel cefotaxime-hydrolyzing beta-lactamase
      (CTX-M-4) was determined. It was located in a plasmid harbored by a Salmonella
      typhimurium strain. CTX-M-4 was similar to the plasmidic cefotaxime-hydrolyzing
      beta-lactamases CTX-M-2 and Toho-1 and related to the chromosomal beta-lactamase
      of Klebsiella oxytoca. A Ser-237-->Ala substitution, introduced by site-directed
      mutagenesis, caused minor alterations in the interaction of CTX-M-4 with beta
      lactams, reducing slightly the relative hydrolytic activity against cefotaxime
      and the susceptibility to inhibition by clavulanate.

PMID- 9593163
TI  - Antipneumococcal activity of grepafloxacin compared to that of other agents by
      time-kill methodology.
AB  - Time-kill studies compared the activities of grepafloxacin with those of
      ciprofloxacin, levofloxacin, sparfloxacin, amoxicillin-clavulanate, and
      clarithromycin against 12 pneumococcal strains. Grepafloxacin was bactericidal
      after 24 h against all strains at a concentration of < or = 0.5 microg/ml, while
      sparfloxacin, levofloxacin, and ciprofloxacin were bactericidal at concentrations
      of < or = 1.0, < or = 2.0, and < or = 8.0 microg/ml, respectively. Amoxicillin
      clavulanate and clarithromycin were bactericidal at 2x the MIC after 24 h against
      12 of 12 strains and against all 8 macrolide-susceptible strains, respectively.

PMID- 9593164
TI  - In vitro antimicrobial effects of various combinations of penicillin and
      clindamycin against four strains of Streptococcus pyogenes.
AB  - Previous studies using mouse models of Streptococcus pyogenes necrotizing
      fasciitis demonstrated that clindamycin had greater efficacy than penicillin.
      Frequently both agents are used concurrently in the treatment of severe S.
      pyogenes infections. This study investigated interactions between penicillin and
      clindamycin. E-test and broth microdilution assays suggested additivity or
      indifference, while timed-killing assays demonstrated concentration-dependent
      variable effects. Timed-kill studies utilizing clinical concentrations suggest
      that there is no antagonism with the combination of drugs but that the
      combination does not have a bactericidal advantage over either penicillin or
      clindamycin alone.

PMID- 9593165
TI  - Comparative activities of clinafloxacin against gram-positive and -negative
      bacteria.
AB  - Activities of clinafloxacin, ciprofloxacin, levofloxacin, sparfloxacin,
      trovafloxacin, piperacillin, piperacillin-tazobactam, trimethoprim
      sulfamethoxazole, ceftazidime, and imipenem against 354 ciprofloxacin-susceptible
      and -intermediate-resistant organisms were tested by agar dilution. Clinafloxacin
      yielded the lowest quinolone MICs (< or = 0.5 microg/ml against ciprofloxacin
      susceptible organisms and < or = 16.0 microg/ml against ciprofloxacin
      intermediate-resistant organisms) compared to those of levofloxacin,
      trovafloxacin, and sparfloxacin. Ceftazidime, piperacillin alone or combined with
      tazobactam, trimethoprim-sulfamethoxazole, and imipenem usually yielded higher
      MICs against ciprofloxacin-resistant strains.

PMID- 9593166
TI  - In vitro activities of clinafloxacin against contemporary clinical bacterial
      isolates from 10 North American centers.
AB  - Clinafloxacin was more active than ciprofloxacin against 4,213 aerobic and
      facultative anaerobic bacterial isolates from 10 medical centers, as tested by
      broth microdilution and disk diffusion methods. The percentage of 201 anaerobes
      susceptible to clinafloxacin by broth microdilution was comparable to cefoxitin.
      Our data support the proposed disk diffusion interpretive criteria for aerobic
      bacteria with 5-microg clinafloxacin disks.

PMID- 9593167
TI  - A triazine dye, cibacron blue F3GA, decreases oxacillin resistance levels in
      methicillin-resistant Staphylococcus aureus.
AB  - Cibacron blue F3GA (CB) was found to reduce the MIC of oxacillin for methicillin
      resistant Staphylococcus aureus (MRSA). This effect was not observed with
      methicillin-susceptible S. aureus. CB alters the resistance level of MRSA through
      a factor(s) other than mecA-related products, major autolysins, or femAB
      products. The exact target(s) of CB in causing the effect is unknown.

PMID- 9593168
TI  - Properties of mutant SHV-5 beta-lactamases constructed by substitution of
      isoleucine or valine for methionine at position 69.
AB  - The effect of replacement of Met-69 by Ile or Val on the properties of the
      extended-spectrum beta-lactamase SHV-5 was studied. Mutant enzymes were
      constructed by site-specific mutagenesis and expressed under isogenic conditions
      in Escherichia coli DH5alpha cells. Compared with SHV-5, the mutant beta
      lactamases conferred lower levels of beta-lactam resistance and were less
      efficient in hydrolyzing ampicillin, cephalothin, and cefotaxime. The
      substitutions rendered SHV-5 less susceptible to inhibition by clavulanate,
      sulbactam, and tazobactam; however, the MICs of penicillin-inhibitor combinations
      remained similar, suggesting an attenuation of penicillinase activity.

PMID- 9593169
TI  - Antibacterial activities and inhibitory effects of sitafloxacin (DU-6859a) and
      its optical isomers against type II topoisomerases.
AB  - The in vitro inhibitory effects of sitafloxacin (DU-6859a) and its three
      stereoisomers on bacterial DNA gyrase from Escherichia coli, topoisomerase IV
      from Staphylococcus aureus, and topoisomerase II from human placenta were
      compared. No correlation was observed between the inhibitory activities of
      quinolones against bacterial type II topoisomerases and those against human
      topoisomerase II. Sitafloxacin showed the most potent inhibitory activities
      against bacterial type II topoisomerases and the lowest activity against human
      type II topoisomerase.

PMID- 9593170
TI  - Tetracycline resistance in Salmonella enterica subsp. enterica serovar Dublin.
AB  - The 47-kbp plasmid pGFT1 from Salmonella enterica subsp. enterica serovar Dublin
      mediated tetracycline resistance via a tet(A) gene located on an integrated copy
      of a Tn1721-analogous transposon. The integration site of the transposon was
      located within the reading frame of a fip gene. Plasmid pGFT1 was shown to be
      conjugative and to be able to replicate and express tetracycline resistance in
      Escherichia coli.

PMID- 9593172
TI  - Prophylaxis of Plasmodium falciparum infection in a human challenge model with WR
      238605, a new 8-aminoquinoline antimalarial.
AB  - The prophylactic efficacy of WR 238605, a primaquine analog, was studied with a
      human Plasmodium falciparum challenge model. A single oral dose of 600 mg,
      administered 1 day prior to challenge, successfully protected three of four
      subjects. The fourth subject developed mild, oligosymptomatic malaria on day 31,
      with drug concentrations one-half of those in the protected individuals. WR
      238605 appears to be a promising prophylactic drug for P. falciparum malaria.

PMID- 9593171
TI  - Susceptibilities of neonatal respiratory isolates of Ureaplasma urealyticum to
      antimicrobial agents.
AB  - Twenty-one neonatal respiratory isolates of Ureaplasma urealyticum were
      serotyped, and their susceptibilities to ciprofloxacin, gentamicin,
      chloramphenicol, erythromycin, azithromycin, and doxycycline were tested. Most
      patient strains were Ureaplasma urealyticum bv. parvum. Chloramphenicol,
      doxycycline, and azithromycin had the lowest MICs. This data may be useful when
      designing prophylactic or therapeutic trials of antibiotics for chronic lung
      disease of the newborn.

PMID- 9593173
TI  - Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis.
AB  - An A1400G mutation of the rrs gene was identified in Mycobacterium tuberculosis
      (MTB) strain ATCC 35827 and in 13 MTB clinical isolates resistant to amikacin
      kanamycin (MICs, >128 microg/ml). High-level cross-resistance may result from
      such a mutation since MTB has a single copy of the rrs gene. Another mechanism(s)
      may account for high-level amikacin-kanamycin resistance in two mutants and lower
      levels of resistance in four clinical isolates, all lacking the A1400G mutation.

PMID- 9593174
TI  - Comparative dispositions of ofloxacin in human head, axillary, and pubic hairs.
AB  - The distribution of ofloxacin (OFLX) along the shaft of each of three hair types,
      i.e., head, axillary and pubic, was investigated and compared among five healthy
      male volunteers 1 to 4 months after ingestion of OFLX for 1 or 2 days (total
      dose, 200 or 600 mg). Five strands of each hair type were sectioned together into
      successive 0.5-cm lengths starting from the dermal end, over a length of < or = 6
      cm, and the OFLX concentration in each hair section was measured by high-pressure
      liquid chromatography with fluorescence detection. The distribution of OFLX along
      the head hair shaft was narrow, having a single peak even 3 to 4 months after
      administration, suggesting a rather uniform growth rate among hair strands. On
      the other hand, the OFLX distribution along axillary or pubic hair shafts tended
      to be broad, even having two apparent peaks, and the growth rate did not seem
      uniform. Since axillary hair seemed to stop growing after having gained a length
      of < or = 4 to 5 cm, it was suggested to enter a resting stage after the growth
      of < or = 3 cm over the 2 to 4 months after OFLX incorporation. These findings
      indicate that head hair is the most suitable for analysis of individual drug use
      and the larger growth rate and cycle stage variabilities of strands of the other
      types of hair should be taken into account.

PMID- 9593175
TI  - Historical yearly usage of vancomycin.

PMID- 9593176
TI  - Characterization of mupirocin-resistant Staphylococcus aureus from different
      geographic areas.

PMID- 9593177
TI  - Analysis of grlA mutations in clinical isolates of Staphylococcus aureus with
      different levels of quinolone resistance.

PMID- 9593179
TI  - Solid-supported syntheses of 3-thio-1,2,4-triazoles.
AB  - Two solid-supported synthesis strategies for the preparation of 3-thio-1,2,4
      triazoles are described. In the first, Rink amide resin is combined with Fmoc
      protected omega-amino acids, acid hydrazides, and alkyl halides to provide
      diverse sets of starting materials from which numerous triazoles may be prepared.
      The second employs t-alkylcarbamate resin (Boc resin) which permits the use of
      additional pools of starting materials, including isothiocyanates and alpha- and
      omega-amino esters, resulting in triazoles with patterns of functional groups
      that are not possible from the initial route. The combination of multiple resins
      and resin attachment sites allows the preparation of a diverse library based upon
      the 3-thio-1,2,4-triazole scaffold and avoids the pitfall of having a single
      linker functionality present at the same position in all library members. General
      synthetic procedures and representative products from each route are presented. A
      similarity analysis of representative sublibraries from each synthesis strategy
      concludes that variation of the solid-phase linker chemistry and attachment site
      can enhance molecular diversity of the combined triazole library.

PMID- 9593178
TI  - Carbohydrate-based combinatorial libraries.
AB  - Carbohydrate-based combinatorial libraries are tremendously valuable for studying
      the role of sugars in biology and for expanding accessible molecular diversity
      needed in broad-based drug screening programs. This review discusses the issues
      that are relevant to the successful implementation of comprehensive carbohydrate
      based combinatorial library programs. In addition, details of oligosaccharide and
      glycoconjugate libraries constructed using both solid phase and solution phase
      strategies are presented.

PMID- 9593180
TI  - The use of high-throughput synthesis and purification in the preparation of a
      directed library of adrenergic agents.
AB  - A library of potential agonists and antagonists for adrenergic receptors was
      prepared using high-throughput solution-phase parallel synthesis. Traditional
      solution-phase reductive amination reactions followed by rapid purification by
      ion exchange chromatography yielded products with near-analytical purity. An
      array of ketones and amines, arranged in an 8 x 12 matrix, were combined to form
      96 individual compounds.

PMID- 9593181
TI  - Solid phase synthesis of functionalized biaryl ethers: versatile scaffolds for
      combinatorial chemistry.
AB  - 4-Fluoro-3-nitrobenzoic acid attached to a solid support was shown to react under
      mild conditions with a wide range of functionalized phenols to yield, after
      cleavage, the corresponding biaryl ethers in excellent purity. In a similar
      fashion, biaryl thioethers could be obtained. Further elaboration of immobilized
      biaryl ethers demonstrates the potential for combinatorial library generation.

PMID- 9593182
TI  - Solid phase synthesis of combinatorial libraries using anhydrides as templates.
AB  - A simple and general approach to the synthesis of chemical libraries based on a
      universal anhydride template allows the preparation of large number of compounds.
      Various cyclic/acyclic amines, primary/secondary amines, differentially protected
      bifunctional amines were used as nucleophiles to react with anhydrides. The free
      carboxylic acid generated was then coupled with solid-bound amines. The facile
      and rapid generation of compounds through this multi-component assembly can be
      accomplished in a combinatorial parallel synthesis.

PMID- 9593183
TI  - Solid phase synthesis of benzamidine and butylamine-derived hydantoin libraries.
AB  - We have constructed a number of benzamidine- and butylamine-based hydantoin
      compounds by means of an efficient route using solid phase synthesis in which
      neat diisopropylamine was employed for a novel cyclization/traceless cleavage
      step. All library compounds were obtained in excellent yield and high purity.

PMID- 9593184
TI  - Solid phase synthesis of benzamidine-derived sulfonamide libraries.
AB  - Using solid phase synthesis, a library has been constructed of benzamidine
      derived sulfonamides which have strong inhibitory activity against blood
      coagulant thrombin. The library compounds were obtained in good yield and high
      purity.

PMID- 9593185
TI  - Urea effects on protein stability: hydrogen bonding and the hydrophobic effect.
AB  - The effects of urea on protein stability have been studied using a model system
      in which we have determined the energetics of dissolution of a homologous series
      of cyclic dipeptides into aqueous urea solutions of varying concentration at 25
      degrees C using calorimetry. The data support a model in which urea denatures
      proteins by decreasing the hydrophobic effect and by directly binding to the
      amide units via hydrogen bonds. The data indicate also that the enthalpy of amide
      hydrogen bond formation in water is considerably higher than previously
      estimated. Previous estimates included the contribution of hydrophobic transfer
      of the alpha-carbon resulting in an overestimate of the binding between urea and
      the amide unit of the backbone and an underestimate of the binding enthalpy.

PMID- 9593186
TI  - Domain motions in bacteriophage T4 lysozyme: a comparison between molecular
      dynamics and crystallographic data.
AB  - A comparison of a series of extended molecular dynamics (MD) simulations of
      bacteriophage T4 lysozyme in solvent with X-ray data is presented. Essential
      dynamics analyses were used to derive collective fluctuations from both the
      simulated trajectories and a distribution of crystallographic conformations. In
      both cases the main collective fluctuations describe domain motions. The protein
      consists of an N- and C-terminal domain connected by a long helix. The analysis
      of the distribution of crystallographic conformations reveals that the N-terminal
      helix rotates together with either of these two domains. The main domain
      fluctuation describes a closure mode of the two domains in which the N-terminal
      helix rotates concertedly with the C-terminal domain, while the domain
      fluctuation with second largest amplitude corresponds to a twisting mode of the
      two domains, with the N-terminal helix rotating concertedly with the N-terminal
      domain. For the closure mode, the difference in hinge-bending angle between the
      most open and most closed X-ray structure along this mode is 49 degrees. In the
      MD simulation that shows the largest fluctuation along this mode, a rotation of
      45 degrees was observed. Although the twisting mode has much less freedom than
      the closure mode in the distribution of crystallographic conformations,
      experimental results suggest that it might be functionally important.
      Interestingly, the twisting mode is sampled more extensively in all MD
      simulations than it is in the distribution of X-ray conformations.

PMID- 9593187
TI  - Crystal structure of the disulfide-stabilized Fv fragment of anticancer antibody
      B1: conformational influence of an engineered disulfide bond.
AB  - A recombinant Fv construct of the B1 monoclonal antibody that recognizes the
      LewisY-related carbohydrate epitope on human carcinoma cells has been prepared.
      The Fv is composed of the polypeptide chains of the VH and VL domains expressed
      independently and isolated as inclusion bodies. The Fv is prepared by combining
      and refolding equimolar amounts of guanidine chloride solubilized inclusion
      bodies. The Fv is stabilized by an engineered interchain disulfide bridge between
      residues VL100 and VH44. This construct has a similar binding affinity as that of
      the single-chain construct (Benhar and Pastan, Clin. Cancer Res. 1:1023-1029,
      1995). The B1 disulfide-stabilized Fv (BldsFv) crystallizes in space group
      P6(1)22 with the unit cell parameters a = b = 80.1 A, and c = 138.1 A. The
      crystal structure of the BldsFv has been determined at 2.1-A resolution using the
      molecular replacement technique. The final structure has a crystallographic R
      value of 0.187 with a root mean square deviation in bond distance of 0.014 A and
      in bond angle of 2.74 degrees. Comparisons of the BldsFv structure with known
      structures of Fv regions of other immunoglobulin fragments shows closely related
      secondary and tertiary structures. The antigen combining site of BldsFv is a deep
      depression 10-A wide and 17-A long with the walls of the depression composed of
      residues, many of which are tyrosines, from complementarity determining regions
      L1, L3, H1, H2, and H3. Model building studies indicate that the LewisY
      tetrasaccharide, Fuc-Gal-Nag-Fuc, can be accommodated in the antigen combining
      site in a manner consistent with the epitope predicted in earlier biochemical
      studies (Pastan, Lovelace, Gallo, Rutherford, Magnani, and Willingham, Cancer
      Res. 51:3781-3787, 1991). Thus, the engineered disulfide bridge appears to cause
      little, if any, distortion in the Fv structure, making it an effective substitute
      for the B1 Fab.

PMID- 9593188
TI  - Influence of protein structure databases on the predictive power of statistical
      pair potentials.
AB  - A long standing goal in protein structure studies is the development of reliable
      energy functions that can be used both to verify protein models derived from
      experimental constraints as well as for theoretical protein folding and inverse
      folding computer experiments. In that respect, knowledge-based statistical pair
      potentials have attracted considerable interests recently mainly because they
      include the essential features of protein structures as well as solvent effects
      at a low computing cost. However, the basis on which statistical potentials are
      derived have been questioned. In this paper, we investigate statistical pair
      potentials derived from protein three-dimensional structures, addressing in
      particular questions related to the form of these potentials, as well as to the
      content of the database from which they are derived. We have shown that
      statistical pair potentials depend on the size of the proteins included in the
      database, and that this dependence can be reduced by considering only pairs of
      residue close in space (i.e., with a cutoff of 8 A). We have shown also that
      statistical potentials carry a memory of the quality of the database in terms of
      the amount and diversity of secondary structure it contains. We find, for
      example, that potentials derived from a database containing alpha-proteins will
      only perform best on alpha-proteins in fold recognition computer experiments. We
      believe that this is an overall weakness of these potentials, which must be kept
      in mind when constructing a database.

PMID- 9593189
TI  - Interaction of transmembrane helices by a knobs-into-holes packing characteristic
      of soluble coiled coils.
AB  - Membrane-embedded protein domains frequently exist as alpha-helical bundles, as
      exemplified by photosynthetic reaction centers, bacteriorhodopsin, and cytochrome
      C oxidase. The sidechain packing between their transmembrane helices was
      investigated by a nearest-neighbor analysis which identified sets of interfacial
      residues for each analyzed helix-helix interface. For the left-handed helix-helix
      pairs, the interfacial residues almost exclusively occupy positions a, d, e, or g
      within a heptad motif (abcdefg) which is repeated two to three times for each
      interacting helical surface. The connectivity between the interfacial residues of
      adjacent helices conforms to the knobs-into-holes type of sidechain packing known
      from soluble coiled coils. These results demonstrate on a quantitative basis that
      the geometry of sidechain packing is similar for left-handed helix-helix pairs
      embedded in membranes and coiled coils of soluble proteins. The transmembrane
      helix-helix interfaces studied are somewhat less compact and regular as compared
      to soluble coiled coils and tolerate all hydrophobic amino acid types to similar
      degrees. The results are discussed with respect to previous experimental findings
      which demonstrate that specific interactions between transmembrane helices are
      important for membrane protein folding and/or oligomerization.

PMID- 9593190
TI  - Comparison of solution and crystal structures of maize nonspecific lipid transfer
      protein: a model for a potential in vivo lipid carrier protein.
AB  - The three-dimensional solution structure of maize nonspecific lipid transfer
      protein (nsLTP) obtained by nuclear magnetic resonance (NMR) is compared to the X
      ray structure. Although both structures are very similar, some local structural
      differences are observed in the first and the fourth helices and in several side
      chain conformations. These discrepancies arise partly from intermolecular
      contacts in the crystal lattice. The main characteristic of nsLTP structures is
      the presence of an internal hydrophobic cavity whose volume was found to vary
      from 237 to 513 A3 without major variations in the 15 solution structures.
      Comparison of crystal and NMR structures shows the existence of another small
      hollow at the periphery of the protein containing a water molecule in the X-ray
      structure, which could play an important structural role. A model of the
      complexed form of maize nsLTP by alpha-lysopalmitoylphosphatidylcholine was built
      by docking the lipid inside the protein cavity of the NMR structure. The main
      structural feature is a hydrogen bond found also in the X-ray structure of the
      complex maize nsLTP/palmitate between the hydroxyl of Tyr81 and the carbonyl of
      the lipid. Comparison of 12 primary sequences of nsLTPs emphasizes that all
      residues delineating the cavities calculated on solution and X-ray structures are
      conserved, which suggests that this large cavity is a common feature of all
      compared plant nsLTPs. Furthermore several conserved basic residues seem to be
      involved in the stabilization of the protein architecture.

PMID- 9593191
TI  - Relationships between protein sequence and structure patterns based on residue
      contacts.
AB  - The identification of correlations between sequence patterns and structural
      motifs is a prerequisite in the development of protein structure prediction
      methods. The prediction accuracy indicates whether these correlations are
      discerned. We present an approach to identify long-range relationships between
      sequence patterns and structural motifs by varying the granulation of the
      structure description. Since interaction among residues is a major determinant in
      protein folding, we consider contact environments formed by two triplets of three
      sequentially neighboring residues and described by vectors whose components
      express contact strengths on an atomic level. Through testing various
      classification schemes, including their resolution and optimizing parameters,
      discernible relationships between sequences and folds are explored. About ten
      structural contact states, together with information from noncontacting regions,
      could improve the accuracy of contact prediction.

PMID- 9593192
TI  - Conformation of the Ras-binding domain of Raf studied by molecular dynamics and
      free energy simulations.
AB  - Recognition of Ras by its downstream target Raf is mediated by a Ras-recognition
      region in the Ras-binding domain (RBD) of Raf. Residues 78-89 in this region
      occupy two different conformations in the ensemble of NMR solution structures of
      the RBD: a fully alpha-helical one, and one where 87-90 form a type IV beta-turn.
      Molecular dynamics simulations of the RBD in solution were performed to explore
      the stability of these and other possible conformations of both the wild-type RBD
      and the R89K mutant, which does not bind Ras. The simulations sample a fully
      helical conformation for residues 78-89 similar to the NMR helical structures, a
      conformation where 85-89 form a 3(10)-helical turn, and a conformation where 87
      90 form a type I beta-turn, whose free energies are all within 0.3 kcal/mol of
      each other. NOE patterns and H(alpha) chemical shifts from the simulations are in
      reasonable agreement with experiment. The NMR turn structure is calculated to be
      3 kcal/mol higher than the three above conformations. In a simulation with the
      same implicit solvent model used in the NMR structure generation, the turn
      conformation relaxes into the fully helical conformation, illustrating possible
      structural artifacts introduced by the implicit solvent model. With the Raf R89K
      mutant, simulations sample a fully helical and a turn conformation, the turn
      being 0.9 kcal/mol more stable. Thus, the mutation affects the population of RBD
      conformations, and this is expected to affect Ras binding. For example, if the
      fully helical conformation of residues 78-89 is required for binding, its free
      energy increase in R89K will increase the binding free energy by about 0.6
      kcal/mol.

PMID- 9593193
TI  - Accessibility to internal cavities and ligand binding sites monitored by protein
      crystallographic thermal factors.
AB  - Protein structures are flexible both in solution and in the solid state. X-ray
      crystallographically determined thermal factors monitor the flexibility of
      protein atoms. A method utilizing such factors is proposed to delineate protein
      regions through which a ligand can exchange between binding site and bulk
      solvent. It is based on the assumption that thermally excited protein regions are
      excellent candidates for opening a ligand channel. Computationally simple and
      inexpensive, the method analyzes directions from which thermal factors can
      propagate within the protein, resulting in thermal motion paths (TMPs).
      Applications to engineered T4 lysozymes, where an artificial internal cavity can
      host hydrophobic molecules, and to sperm whale myoglobins, where the active site
      is completely buried, yielded results in agreement with other independent
      structural observations and with previous hypotheses. Further new features could
      also be suggested. The proposed TMP analysis could aid molecular dynamics
      simulation studies as well as time-resolved and site-directed mutagenesis
      experimental studies, especially given its modest computational expense and its
      direct roots in experimental results based on thermal factors determined in high
      resolution crystallographic studies.

PMID- 9593194
TI  - Circular permutants in beta-glucosidases (family 3) within a predicted double
      domain topology that includes a (beta/alpha)8-barrel.
AB  - By predicting the general secondary structure for beta-glucosidases (family 3),
      in conjunction with existing knowledge of the circular permutants present in B.
      fibrisolvens and R. albus, we were able to find the canonical elements of the
      secondary structure. The way these elements are linked suggests that there is a
      double-domain topology made up of a (beta/alpha)8-barrel domain and a "mainly all
      beta" domain. A number of already known conserved motifs are located within (or
      near) the C-terminal part of the putative parallel beta-strands of the
      (bet/alpha)8-barrel, which is consistent with what is known about the location of
      catalytical sites for enzymes that have this domain topology. Within the circular
      permutants, two beta/alpha units are located at the N-terminal part of the
      molecule, whereas the other six beta/alpha units are located at the C-terminal
      end. In this way, the circular permutants can be seen to have a putative
      discontinuous double-domain topology.

PMID- 9593196
TI  - Protein folding simulation with genetic algorithm and supersecondary structure
      constraints.
AB  - We describe an algorithm to compute native structures of proteins from their
      primary sequences. The novel aspects of this method are: 1) The hydrophobic
      potential was set to be proportional to the nonpolar solvent accessible surface.
      To make computation feasible, we developed a new algorithm to compute the solvent
      accessible surface areas rapidly. 2) The supersecondary structures of each
      protein were predicted and used as restraints during the conformation searching
      processes. This algorithm was applied to five proteins. The overall fold of these
      proteins can be computed from their sequences, with deviations from crystal
      structures of 1.48-4.48 A for C(alpha) atoms.

PMID- 9593195
TI  - Are knowledge-based potentials derived from protein structure sets discriminative
      with respect to amino acid types?
AB  - The parametric description of residue environments through solvent accessibility,
      backbone conformation, or pairwise residue-residue distances is the key to the
      comparison between amino acid types at protein sequence positions and residue
      locations in structural templates (condition of protein sequence-structure
      match). For the first time, the research results presented in this study clarify
      and allow to quantify, on a rigorous statistical basis, to what extent the amino
      acid type-specific distributions of commonly used environment parameters are
      discriminative with respect to the 20 amino acid types. Relying on the Bahadur
      theory, we estimate the probability of error in a single-sequence-structure
      alignment based on weak or absent discriminative power in a learning database of
      protein structure. We present the results for many residue environment variables
      and demonstrate that each fold description parameter is sensitive with respect to
      only a few amino acid types while indifferent to most of the other amino acid
      types. Even complex structural characteristics combining solvent-accessible
      surface area, backbone conformation, and pairwise distances distinguish only some
      amino acid types, whereas the others remain nondiscriminated. We find that the
      knowledge-based potentials currently in use treat especially Ala, Asp, Gln, His,
      Ser, Thr, and Tyr as essentially "average" amino acids. Thus, highly
      discriminative amino acid types define the alignment register in gapless sequence
      structure alignments. The introduction of gaps leads to alignment ambiguities at
      sequence positions occupied by nondiscriminated amino acid types. Therefore,
      local sequence-structure alignments produced by techniques with gaps cannot be
      reliable. Conceptionally new and more sensitive environment parameters must be
      invented.

PMID- 9593197
TI  - High-resolution solution structure of Bacillus subtilis IIAglc.
AB  - The high-resolution solution structure of the phosphocarrier protein IIAglc from
      Bacillus subtilis is determined using 3D and 4D heteronuclear NMR methods. B.
      subtilis IIAglc contains 162 amino acid residues and is one of the larger
      proteins for which high-resolution solution structure has been determined by NMR
      methods. The structures have been calculated from a total of 2,232 conformational
      constraints. Comparison with the X-ray crystal structure indicates that the
      overall fold is the same in solution and in crystalline environments, although
      some local structural differences are observed. These occur largely in turns and
      loops, and mostly correspond to regions with high-temperature factors in the
      crystal structure. The N-terminus of IIAglc is disordered in solution. The active
      site is located in a concave region of the protein surface. The histidine, which
      accepts the phosphoryl group (His 83), interacts with a neighboring histidine
      (His 68) and is surrounded by hydrophobic residues.

PMID- 9593198
TI  - Coarse-grained simulations of conformational dynamics of proteins: application to
      apomyoglobin.
AB  - A coarse-grained dynamic Monte Carlo method is proposed for investigating the
      conformational dynamics of proteins. Each residue is represented by two
      interaction sites, one at the alpha-carbon, and the other on the amino acid
      sidechain. Geometry and energy parameters extracted from databank structures are
      used. The method is applied to the crystal structure of apomyoglobin (apo-Mb).
      Equilibrium and dynamic properties of apo-Mb are characterized within computation
      times one order of magnitude shorter than conventional molecular dynamics (MD)
      simulations. The calculated rms fluctuations in alpha-carbons are in good
      agreement with crystallographic temperature factors. Regions exhibiting enhanced
      conformational mobilities are identified. Among the loops connecting the eight
      helices A to H, the loop CD undergoes the fastest motions, leading to partial
      unwinding of helix D. Helix G is the most stable helix on the basis of the
      kinetic stability of dihedral angles, followed by the respective helices A, E, H,
      and B. These results, in agreement with H/D exchange and two-dimensional NMR
      experiments, as well as with MD simulations, lend support to the use of the
      proposed approach as an efficient, yet physically plausible, means of
      characterizing protein conformational dynamics.

PMID- 9593199
TI  - Fragment-based modeling of NAD binding to the catalytic subunits of diphtheria
      and pertussis toxins.
AB  - We describe a novel application of a fragment-based ligand docking technique;
      similar methods are commonly applied to the de novo design of ligands for target
      protein binding sites. We have used several new flexible docking and
      superposition tools, as well as a more conventional rigid-body (fragment) docking
      method, to examine NAD binding to the catalytic subunits of diphtheria (DT) and
      pertussis (PT) toxins, and to propose a model of the NAD-PT complex. Docking
      simulations with the rigid NAD fragments adenine and nicotinamide revealed that
      the low-energy dockings clustered in three distinct sites on the two proteins.
      Two of the sites were common to both fragments and were related to the structure
      of NAD bound to DT in an obvious way; however, the adenine subsite of PT was
      shifted relative to that of DT. We chose adenine/nicotinamide pairs of PT
      dockings from these clusters and flexibly superimposed NAD onto these pairs. A
      Monte Carlo-based flexible docking procedure and energy minimization were used to
      refine the modeled NAD-PT complexes. The modeled complex accounts for the
      sequence and structural similarities between PT and DT and is consistent with
      many results that suggest the catalytic importance of certain residues. A
      possible functional role for the structural difference between the two complexes
      is discussed.

PMID- 9593200
TI  - Extracting contact energies from protein structures: a study using a simplified
      model.
AB  - In this study, we exploited an elementary 2-dimensional square lattice model of
      HP polymers to test the premise of extracting contact energies from protein
      structures. Given a set of prespecified energies for H-H, H-P, and P-P contacts,
      all possible sequences of various lengths were exhaustively enumerated to find
      sequences that have unique lowest-energy conformations. The lowest-energy
      structures (or native structures) of such (native) sequences were used to extract
      contact energies using the Miyazawa-Jernigan procedure and here-defined reference
      state. The relative magnitudes of the original energies were restored reasonably
      well, but the extracted contact energies were independent of the absolute
      magnitudes of the initial energies. We turned to a more detailed characterization
      of the energy landscapes of the native sequences in light of a new theoretical
      framework on protein folding. Foldability of such sequences imposes two limits on
      the absolute value of the prespecified energies: a lower bound entailed by the
      minimum requirement for thermodynamic stability and an upper bound associated
      with the entrapment of the chain to local minima. We found that these two limits
      confine the prespecified energy values to a rather narrow range which,
      surprisingly, also contains the extracted energies in all the cases examined.
      These results indicate that the quasi-chemical approximation can be used to
      connect quantitatively the occurrence of various residue-residue contacts in an
      ensemble of native structures with the energies of the contacts. More
      importantly, they suggest that the extracted contact energies do contain
      information on structural stability and can be used to estimate actual structural
      energetics. This study also encourages the use of structure-derived contact
      energies in threading. The finding that there is a rather narrow range of
      energies that are optimal for folding a sequence also cautions the use of
      arbitrary energy Hamiltonion in minimal folding models.

PMID- 9593201
TI  - Thermal unfolding of small proteins with SH3 domain folding pattern.
AB  - The thermal unfolding of three SH3 domains of the Tec family of tyrosine kinases
      was studied by differential scanning calorimetry and CD spectroscopy. The
      unfolding transition of the three protein domains in the acidic pH region can be
      described as a reversible two-state process. For all three SH3 domains maximum
      stability was observed in the pH region 4.5 < pH < 7.0 where these domains unfold
      at temperatures of 353K (Btk), 342K (Itk), and 344K (Tec). At these temperatures
      an enthalpy change of 196 kJ/mol, 178 kJ/mol, and 169 kJ/mol was measured for Btk
      , Itk-, and Tec-SH3 domains, respectively. The determined changes in heat
      capacity between the native and the denatured state are in an usual range
      expected for small proteins. Our analysis revealed that all SH3 domains studied
      are only weakly stabilized and have free energies of unfolding which do not
      exceed 12-16 kJ/mol but show quite high melting temperatures. Comparing unfolding
      free energies measured for eukaryotic SH3 domains with those of the topologically
      identical Sso7d protein from the hyperthermophile Sulfolobus solfataricus, the
      increased melting temperature of the thermostable protein is due to a broadening
      as well as a significant lifting of its stability curve. However, at their
      physiological temperatures, 310K for mesophilic SH3 domains and 350K for Sso7d,
      eukaryotic SH3 domains and Sso7d show very similar stabilities.

PMID- 9593202
TI  - Packing forces in nine crystal forms of cutinase.
AB  - During the characterization of mutants and covalently inhibited complexes of
      Fusarium solani cutinase, nine different crystal forms have been obtained so far.
      Protein mutants with a different surface charge distribution form new
      intermolecular salt bridges or long-range electrostatic interactions that are
      accompanied by a change in the crystal packing. The whole protein surface is
      involved in the packing contacts and the hydrophobicities of the protein surfaces
      in mutual contact turned out to be noncorrelated, which indicates that the
      packing interactions are nonspecific. In the case of the hydrophobic variants,
      the packing contacts showed some specificity, as the protein in the crystal tends
      to form either crystallographic or noncrystallographic dimers, which shield the
      hydrophobic surface from the solvent. The likelihood of surface atoms to be
      involved in a crystal contact is the same for both polar and nonpolar atoms.
      However, when taking areas in the 200-600 A2 range, instead of individual atoms,
      the either highly hydrophobic or highly polar surface regions were found to have
      an increased probability of establishing crystal lattice contacts. The protein
      surface surrounding the active-site crevice of cutinase constitutes a large
      hydrophobic area that is involved in packing contacts in all the various
      crystalline contexts.

PMID- 9593203
TI  - A model for loading-dependent growth, development, and adaptation of tendons and
      ligaments.
AB  - The geometric and material properties of tendons and ligaments change during
      growth and development. While some of the changes occur in the absence of
      mechanical loading, normal development requires the mechanical stimulus provided
      by normal physical activity. We have developed an analytical framework for
      quantitatively describing changes in uniaxial tendon and ligament properties
      throughout ontogeny. In our approach, cross-sectional area, modulus, and strength
      undergo baseline levels of development due to inherent time-dependent biological
      influences. The properties also change in response to mechanobiological
      influences by adapting to maintain a constant daily strain stimulus under
      changing load conditions. We have implemented a computer algorithm based on these
      concepts and obtained results consistent with experimental observations of normal
      tendon and ligament growth and development reported by other investigators.
      Additional results suggest that these concepts can also explain tendon and
      ligament adaptation to increased or decreased loading experienced during
      development.

PMID- 9593204
TI  - The role of elastin in aortic valve mechanics.
AB  - Recent morphologic observations of elastin structures in aortic valves suggest
      that elastin is mechanically coupled to collagen. Since the mechanical stiffness
      of elastin is considerably lower than that of collagen, and aortic valves contain
      relatively little elastin, the mechanical importance of elastin in heart valve
      function is not clear. We have hypothesized that elastin acts to return the
      collagen fiber structure back to a resting configuration between loading cycles.
      The objectives of this research were therefore to elucidate the mechanical
      relationship between elastin and collagen structures within the aortic valve. To
      isolate elastin in a morphologically intact state, whole porcine aortic valve
      leaflets were digested in 0.1 N sodium hydroxide solution (NaOH) at a temperature
      of 75 degrees C for 45 min. Elastin structures from the fibrosa and ventricularis
      were tested mechanically, and their loading curves compared to those of the
      original leaflet layers and to whole cusps. The elastin structures generated very
      low forces, having an elastic modulus only 0.05% that of the whole tissue. The
      contribution of elastin to tissue mechanics was significant at low strains and
      differed between the fibrosa and the ventricularis. Elastin tended to dominate
      the distensibility curves of the radial ventricularis, but participated very
      little in the fibrosa. The low but significant tensions produced by the elastin
      structures of the aortic valve, together with previously observed elastin
      morphology as well as the measurable preload of elastin, suggest that the purpose
      of elastin in the aortic valve leaflet is to maintain a specific collagen fiber
      configuration and return the fibers to this state, once external forces have been
      released.

PMID- 9593205
TI  - Prediction of femoral fracture load using automated finite element modeling.
AB  - Hip fracture is an important cause of morbidity and mortality among the elderly.
      Current methods of assessing a patient's risk of hip fracture involve local
      estimates of bone density (densitometry), and are limited by their inability to
      account for the complex structural features of the femur. In an effort to improve
      clinical and research tools for assessing hip fracture risk, this study
      investigated whether automatically generated, computed tomographic (CT) scan
      based finite element (FE) models can be used to estimate femoral fracture load in
      vitro. Eighteen pairs of femora were examined under two loading conditions one
      similar to loading during the stance phase of gait, and one simulating impact
      from a fall. The femora were then mechanically tested to failure and regression
      analyses between measured fracture load and FE-predicted fracture load were
      performed. For comparison, densitometry measures were also examined. Significant
      relationships were found between measured fracture load and FE-predicted fracture
      load (r = 0.87, stance; r = 0.95, fall; r = 0.97, stance and fall data pooled)
      and between measured fracture load and densitometry data (r = 0.78, stance; r =
      0.91, fall). These results indicate that this sophisticated technique, which is
      still early in its development, can achieve precision comparable to that of
      densitometry and can predict femoral fracture load to within -40% to +60% with
      95% confidence. Therefore, clinical use of this approach, which would require
      additional X-ray exposure and expenditure for a CT scan, is not justified at this
      point. Even so, the potential advantages of this CT/FE technique support further
      research in this area.

PMID- 9593206
TI  - Strain-structure relations in human teeth using Moire fringes.
AB  - Teeth are subjected to stress during normal function. The manner in which the
      resulting strain is distributed within the tooth is related to its structure. The
      Moire fringe technique was used to map the in-plane strain distribution in slices
      from human tooth crowns under compression. The strain inside enamel is much less
      than in dentin, and there is a roughly 200 microm thick zone in dentin beneath
      the dentin enamel junction which undergoes larger strain than the central coronal
      dentin. This zone is softer and less mineralized than the bulk of the dentin. The
      strain distribution in this zone along the dentin-enamel junction shows localized
      maxima on both the lingual and the labial sides. This study is consistent with
      the hypothesis that within the dentin there are structural adaptations for
      transferring and minimizing stress.

PMID- 9593207
TI  - Resonance behaviour of the seated human body and effects of posture.
AB  - Understanding of the resonance behaviour of the human body is important in the
      identification of vibration frequencies and body postures associated with back
      problems. In this study, experimental modal analysis was applied to whole-body
      vibration. Eight subjects were exposed to vertical random vibration while
      adopting three different postures on a rigid seat without a backrest. Motions of
      the spine, pelvis and viscera in the mid-sagittal plane were derived from skin
      mounted accelerometers; head responses were measured using a bite-bar. Eight
      modes of vibration response were extracted below 10 Hz. A principal resonance of
      the human body at about 5 Hz consisted of an entire body mode, in which the
      skeleton moved vertically due to axial and shear deformations of buttocks tissue,
      in phase with a vertical visceral mode, and a bending mode of the upper thoracic
      and cervical spine. A bending mode of the lumbar and lower thoracic spine was
      found with a pitching mode of the head in the next higher mode located close to
      the principal mode. The second principal resonance at about 8 Hz corresponded to
      pitching modes of the pelvis and a second visceral mode. When subjects changed
      posture from erect to slouched, the natural frequency of the entire body mode
      decreased, resulting in a decrease in the principal resonance frequency. Shear
      deformation of buttocks tissue increased in the entire body mode due to the same
      change of posture. The complex body motions suggest that any forces causing
      injury from whole-body vibration will not be well-predicted by biodynamic models
      incapable of representing the appropriate body motions and the effects of body
      posture. It seems likely that the greatest risk of back problems will arise from
      the bending deformations of the spine.

PMID- 9593208
TI  - A possible physical mechanism of red blood cell vesiculation obtained by
      incubation at high pH.
AB  - The membrane of human red blood cells is essentially composed of two parts, the
      lipid bilayer and the membrane skeleton that interacts with the lipid bilayer.
      The normal resting shape of the red blood cells at physiological pH 7.4 is the
      discocyte. However, at alkaline pH approximately equal to 11 the shape of red
      blood cells is composed of a spherical parent cell and large spherical daughter
      vesicles. The daughter vesicles may be free or connected to the parent cell by a
      narrow neck. In this paper we show that the shapes of red blood cells at pH
      approximately equal to 11 correspond to some of the calculated shapes of a closed
      lipid bilayer having an extreme area difference between the outer and the inner
      monolayer. Therefore, it is suggested that the observed shapes of the red blood
      cells at pH approximately equal to 11 are a consequence of the abolishment of the
      skeleton bilayer interactions at this pH.

PMID- 9593209
TI  - Comparison of two methods for computing abduction moment arms of the rotator
      cuff.
AB  - Biomechanical models of the shoulder mechanism require estimates of muscle moment
      arm magnitude. Some shoulder models have estimated muscle moment arms by assuming
      an idealized minimum distance path from the origin to insertion that passes
      around the bony geometry. Alternatively, the principle of virtual work can be
      used to estimate moment arms from tendon excursion and joint-angle data. The
      purpose of this study was to determine if these two methods give different
      estimates of abduction moment arms for the supraspinatus, infraspinatus, and
      subscapularis muscles. Muscle moment arms were estimated for these muscles on ten
      fresh frozen cadaver specimens. The results showed a significant difference
      between the two estimation methods. Average differences were 3.1 mm (10.6%), 3.9
      mm (43.9%), and 7.2 mm (70.3%) for the supraspinatus, subscapularis, and
      infraspinatus muscles, respectively. These results suggest that shoulder models
      based on the origin-insertion method may give higher rotator cuff muscle force
      estimates than methods using the slope of the tendon excursion vs joint angle
      relationship.

PMID- 9593210
TI  - An algorithm for determining gravity line location from posturographic
      recordings.
AB  - In posturographic recordings, the center of pressure (COP) displacement does not
      accurately reflect migration of the gravity line (GL), the vertical line passing
      through the body's center of gravity, COG. Since the horizontal ground reaction
      force, Fx, is proportional to the horizontal acceleration of the COG its second
      integral does represent the horizontal position of the gravity line (GLP).
      However, the initial constants of integration, initial velocity and position, are
      not known. In this note, a technique for estimating these integration constants
      is suggested: zero-point-to-zero-point integration. This method is based on a
      postulation that when Fx = 0, the GLP and COP coincide. By integrating Fx from
      one zero point to another zero point, both the instantaneous GLP and its velocity
      are determined. A validation of the suggested algorithm was performed using
      optical methods to determine the GLP during a one legged standing tasks. Cross
      correlation values of GLP determined via videography and the suggested algorithm
      ranged from 0.79 to 0.96. These results suggest that the zero-point-to-zero-point
      integration is an acceptable technique for determining GLP from posturographic
      recordings.

PMID- 9593211
TI  - Evaluation of the finite element software ABAQUS for biomechanical modelling of
      biphasic tissues.
AB  - The biphasic cartilage model proposed by Mow et al. (1980) has proven successful
      to capture the essential mechanical features of articular cartilage. In order to
      analyse the joint contact mechanics in real, anatomical joints, the cartilage
      model needs to be implemented into a suitable finite element code to approximate
      the irregular surface geometries of such joints. However, systematic and
      extensive evaluation of the capacity of commercial software for modelling the
      contact mechanics with biphasic cartilage layers has not been made. This research
      was aimed at evaluating the commercial finite element software ABAQUS for
      analysing biphasic soft tissues. The solutions obtained using ABAQUS were
      compared with those obtained using other finite element models and analytical
      solutions for three numerical tests: an unconfined indentation test, a test with
      the contact of a spherical cartilage surface with a rigid plate, and an axi
      symmetric joint contact test. It was concluded that the biphasic cartilage model
      can be implemented into the commercial finite element software ABAQUS to analyse
      practical joint contact problems with biphasic articular cartilage layers.

PMID- 9593212
TI  - Confined compression of articular cartilage: linearity in ramp and sinusoidal
      tests and the importance of interdigitation and incomplete confinement.
AB  - Experimental and theoretical methods were used to investigate the linearity of
      the stress response of articular cartilage to ramp and sinusoidal tests in
      confined compression, as well as the role of cartilage-porous platen and lateral
      confinement boundary conditions in determining material responses. With respect
      to linearity, we posed the question as to whether the elicited stress responses
      to ramp compression, ramp release and sinusoidal tests were similar. With respect
      to boundary conditions we inquired as to the necessity of specifying a detailed
      interdigitating contact with the porous filter and of specifying the level of
      confinement present at the lateral edge of the disk. We found that the stress
      responses to the three types of tests were dissimilar, with ramp compression the
      only test exhibiting linear behavior. Ramp release from a static compression
      offset was non-linear in a manner such that the cartilage maintained a
      compressive stress higher than expected by a linear theory. Sinusoidal
      compression also displayed a non-linear response consistent with the presence of
      a release phase in each cycle. The actual boundary conditions present at the
      cartilage/porous-filter interface were visualized histologically. Areas (tens of
      microns) of cartilage in contact with the metal of the filter were interspersed
      with areas expanded into the pores of the filter. Finite-element analysis
      incorporating this information suggested that precise specification of this
      interface and of the level of the extent of lateral confinement would be
      necessary for the estimation of material properties, such as the hydraulic
      permeability, from these tests. The trends of the linearity studies did not
      appear to be significantly affected by the problems posed by these difficult to
      quantitate boundary conditions. The non-linear cartilage response to release and
      sinusoidal displacements therefore appear to be physiologically interesting. The
      maintained, that is higher than would be linear, compressive stress observed
      during release may be a beneficial adaptation to repeated loading where temporal
      variations in tissue stresses would be minimized.

PMID- 9593213
TI  - Computational blood flow modelling: errors associated with reconstructing finite
      element models from magnetic resonance images.
AB  - Construction of computational blood flow models from magnetic resonance (MR)
      scans of real arteries is a powerful tool for studying arterial hemodynamics. In
      this report we experimentally determine a lower bound for errors associated with
      such an approach, and present techniques for minimizing such errors. A known,
      simple three-dimensional geometry (cylindrical tube) was imaged using a
      commercial MR scanner, and the resulting images were used to construct finite
      element flow models. Computed wall-shear stresses were compared to known values
      and peak errors of 40-60% were found. These errors can be attributed to limited
      spatial resolution, image segmentation and model construction. A simple smoothing
      technique markedly reduced these peak errors. We conclude that smoothing is
      required in the construction of arterial models from in vivo MR images. If used
      appropriately, such images can be used to construct acceptably accurate
      computational models of realistic arterial geometries.

PMID- 9593214
TI  - Mathematical model of the lower extremity joint reaction forces using Kane's
      method of dynamics.
AB  - This report describes a new mathematical model for defining the joint reaction
      forces of the lower extremity using Kane's method of dynamics. Our model utilized
      average lower extremity joint motion and force/plate data from one healthy female
      patient during gait. From a cadaver specimen, the anatomical mass centers of the
      pelvis, femur, tibia, and foot were determined. Joint angular motion during the
      normal gait cycle was computed using Cardan angles for each distal segment
      relative to the proximal segment. Fluoroscopy of four normal knees determined
      average femorotibial and patellofemoral contact positions throughout flexion. A
      three-dimensional model of the lower extremity was defined in weight-bearing
      motion by 30 differential equations. During normal walking, the joint reaction
      forces for the subject tested ranged from 1.9 to 2.6 times body weight at the hip
      joint and 1.7-2.3 times body weight at the knee joint, depending primarily on
      gait speed. The method correlates well with known in vivo telemetrically measured
      forces at the hip joint.

PMID- 9593215
TI  - Can total work be computed as a sum of the 'external' and 'internal' work?

PMID- 9593216
TI  - Positive work and its efficiency are at their dead-end: comments on a recent
      discussion.

PMID- 9593217
TI  - Evidence for the existence of the beta-endorphin-sensitive "epsilon-opioid
      receptor" in the brain: the mechanisms of epsilon-mediated antinociception.
AB  - Recently, mu-, delta- and kappa-opioid receptors have been cloned and relatively
      well-characterized. In addition to three major opioid receptor types, more
      extensive studies have suggested the possible existence of other opioid receptor
      types that can be classified as non-mu, non-delta and non-kappa. Based upon
      anatomical and binding studies in the brain, the sensitive site for an endogenous
      opioid peptide, beta-endorphin, has been postulated to account for the unique
      characteristics of the opioid receptor defined as a putative epsilon-opioid
      receptor. Many epsilon-opioid receptors are functionally coupled to G-proteins.
      The functional epsilon-opioid receptors in the brain are stimulated by
      bremazocine and etorphine as well as beta-endorphin, but not by selective mu-,
      delta- or kappa-opioid receptor agonists. Epsilon-opioid receptor agonists
      injected into the brain produce profound antinociception. The brain sites most
      sensitive to epsilon-agonist-induced antinociception are located in the caudal
      medial medulla such as the nucleus raphe obscures, nucleus raphe pallidus and the
      adjacent midline reticular formation. The stimulation of epsilon-opioid receptors
      in the brain facilitates the descending enkephalinergic pathway, which probably
      originates from the brainstem terminating at the spinal cord. The endogenous
      opioid Met-enkephalin, released in the spinal cord by activation of supraspinal
      epsilon-opioid receptors, stimulates spinal delta2-opioid receptors for the
      production of antinociception. It is noteworthy that the epsilon-opioid receptor
      mediated pain control system is different from that of other opioid systems.
      Although there appears to be no epsilon-selective ligand currently available,
      these findings provide strong evidence for the existence of the putative epsilon
      opioid receptor and its unique function in the brain.

PMID- 9593218
TI  - Pleckstrin homology domain as an inositol compound binding module.
AB  - Many of the proteins that participate in cell signalling contain structural
      modules involved in regulatory interactions between components of signal
      transduction cascades. One of such modules is the pleckstrin homology (PH)
      domain, a region of approximately 120 amino acids that can form an
      electrostatically polarized tertiary structure. Several molecules such as
      inositol 1,4,5-trisphosphate/phosphatidylinositol 4,5-bisphosphate, the betagamma
      subunits of heterotrimeric G proteins and protein kinase C have been proposed as
      common ligands for the PH domain. Through these potential interactions, the PH
      domain has been proposed to play a role in membrane recruitment of proteins
      containing the PH domain, thus targeting them to appropriate cellular compartment
      or enabling them to interact with other components of the signal transduction
      pathway. In this review, we mainly focus on membrane targeting through the
      binding to inositol phosphates/phosphoinositides.

PMID- 9593219
TI  - Effects of the novel tricyclic quinoxalinedione derivatives, SM-18400 and its
      analogs, on N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission
      in the isolated neonatal rat spinal cord in vitro.
AB  - We examined the effects of novel tricyclic quinoxalinedione derivatives, SM-18400
      ((S)-9-chloro-5-[p-aminomethyl-o-(carboxymethoxy)phenylcarbamoylmethy l]-6,7
      dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-dione hydrochloride trihydrate) and
      its analogs (i.e., ID-17263 and ID-17332), on the N-methyl-D-aspartate (NMDA)
      receptor-mediated polysynaptic reflex (PSR) in the isolated spinal cord of
      neonatal rats in vitro. Application of SM-18400 selectively suppressed the PSR
      activity in a concentration-dependent manner without affecting the monosynaptic
      reflex (MSR). Differential suppression of the PSR was also obtained with ID
      17263, ID-17332 and other known NMDA receptor glycine-binding site antagonists,
      5,7-dichlorokynurenate (5,7-diClkyn) and L-689,560 (4-trans-2-carboxy-5,7
      dichloro-4-phenylaminocarbonylamino-1,2,3,4 -tetrahydroquinoline). Relative
      potencies of the test drugs for inhibition of the PSR were as follows: SM-18400
      >> L-689,560 > ID-17332 > ID-17263 > 5,7-diClkyn. In addition, the inhibitory
      effects of SM-18400 on PSR were markedly antagonized by simultaneous application
      of D-serine, an agonist for NMDA receptor glycine-binding sites. These findings
      suggest that SM-18400 is a potent NMDA receptor glycine-binding site antagonist
      and blocks the NMDA receptor-mediated synaptic neurotransmission in the spinal
      cord in vitro.

PMID- 9593220
TI  - Treatment with bovine gallstones exacerbates liver damage, but enhances
      hepatoprotection by bear gall powder in carbon tetrachloride-intoxicated rats.
AB  - The interactions between bovine gallstones (Goou) and bear gall powder (Yutan) in
      decreases in serum transaminase levels were investigated in rats intoxicated with
      carbon tetrachloride (CCl4). The p.o. administration of Goou significantly
      increased both serum transaminase levels and hepatic lipid peroxidation following
      i.p. administration of CCl4. Concomitant administration of both Goou and Yutan
      resulted in decreases of serum transaminase levels and hepatic lipid
      peroxidation, which were more remarkable than with administration of Yutan alone.
      Goou significantly increased the estimated hepatic blood flow in the indocyanine
      green clearance test and enhanced the delivery of CCl4 to the liver from the
      peritoneal cavity. These findings suggest that Goou exacerbates CCl4-induced
      hepatic damage because of the accelerated delivery of CCl4 to the liver and that
      Goou might have a hemodynamic drug interaction with Yutan in the liver, possibly
      enhancing the hepatoprotective effect of Yutan.

PMID- 9593221
TI  - Effects of rabeprazole, a gastric proton pump inhibitor, on biliary and hepatic
      lysosomal enzymes in rats.
AB  - The effects of rabeprazole (E3810), omeprazole and chloroquine on hepatic
      lysosomal function were studied. After chloroquine (50 mg/kg), rabeprazole (5
      mg/kg) or omeprazole (5 mg/kg) was given intraperitoneally to rats for 6 days,
      the bile was collected via a bile duct cannula for 5 hr, and hepatic and biliary
      lysosomal enzyme (N-acetyl-beta-glucosaminidase and beta-galactosidase)
      activities were measured. The latency (an index for the hepatic lysosomal
      membrane integrity) was calculated from the N-acetyl-beta-glucosaminidase
      activity. The biliary constituents and plasma concentrations of lipids were also
      measured. The administration of chloroquine significantly increased hepatic and
      biliary lysosomal enzyme activities, but did not affect the lysosomal enzyme
      latency, hepatic and biliary protein content or bile flow. It significantly
      decreased the bile acid level. On the other hand, the administration of
      rabeprazole and omeprazole did not alter the lysosomal enzyme activities,
      lysosomal enzyme latency, protein content in liver or liver weight. Furthermore,
      no significant differences were observed in biliary lysosomal enzyme activity,
      protein content, bile flow, biliary constituents or in the plasma concentrations
      of lipids between the drug groups (rabeprazole or omeprazole) and the control
      group. The results of the present study indicate that rabeprazole, like
      omeprazole, does not influence hepatic lysosomal function.

PMID- 9593222
TI  - Radioligand binding characteristics of the endothelin receptor in the rabbit
      iris.
AB  - We previously suggested the presence of functionally atypical endothelin (ET) A
      receptors in the rabbit iris sphincter. Here, we further characterized the ET
      receptor by a radioligand-receptor binding study utilizing a membrane fraction of
      the rabbit iris. In addition, we functionally confirm the presence of an atypical
      ET(A) receptor in the iris dilator similar to that in the iris sphincter. In
      binding experiments, [125I]ET-1 was completely displaced by ET-3 in a biphasic
      fashion, but only partially by BQ-123 and ET(B) ligands. In the presence of RES
      701, ET-3 and sarafotoxin (SRTX)-b completely displaced [125I]ET-1 in a
      monophasic fashion, but with shallow slopes. Moreover, ET-1, ET-3 and SRTX-b
      completely displaced [3H]BQ-123 with IC50 values of 0.8, 81 and 4.4 nM,
      respectively, but with slopes of ET-3 and SRTX-b being again shallow. In iris
      dilator muscles, ET-3 showed lower and SRTX-b showed higher contractile
      activities than ET-1. SRTX-c was inactive. BQ-123 more preferentially antagonized
      ET-3 and SRTX-b than ET-1, with the Schild plot slope of SRTX-b being shallow.
      Thus, functional experiments suggested the presence of atypical ET(A) receptors
      in the iris dilator similar to the iris sphincter. However, the binding
      experiments suggested the presence of rather typical ET(A)- and ET(B)-like
      receptors. Therefore, we apparently failed to show ET binding sites corresponding
      to functionally atypical ET(A) receptors.

PMID- 9593223
TI  - Effect of 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole
      HCl (MKC-242), a novel 5-HT1A-receptor agonist, on aggressive behavior and marble
      burying behavior in mice.
AB  - Behavioral effects of 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3
      be nzodioxole HCl (MKC-242), a novel 5-HT1A-receptor agonist, were evaluated
      using animal models of anxiety and obsessive compulsive disorder and compared
      against reference compounds. MKC-242 suppressed foot shock-induced fighting
      behavior without loss of motor coordination in mice as the reference compounds
      did. The ED50 values of MKC-242, buspirone, tandospirone and diazepam were 1.7,
      42, 80 and 2.0 mg/kg, p.o., respectively. The duration of the suppression of
      fighting by MKC-242 was longer than those of buspirone and tandospirone and
      comparable to that of diazepam. Similar results were also obtained with the water
      lick conflict test in rats. The plasma concentration of MKC-242 in rats was much
      higher than the reported value of buspirone during 0.25-6 hr after oral
      administration. In addition, MKC-242 reduced marble burying behavior without
      reduction of motor activity. Fluoxetine, tandospirone and diazepam also reduced
      the behavior at non-sedative doses. These findings indicate that MKC-242
      possesses a longer-lasting anxiolytic effect than azapirones. This might be due
      to the high concentration of the compound in plasma. In addition, it is also
      suggested that MKC-242 possesses an antiobsessional effect.

PMID- 9593224
TI  - Psychological stress induces heat shock protein 70 expression in rat aorta.
AB  - Psychological stress without any physical stimuli caused a rapid and marked
      increase in the level of heat shock protein (HSP) 70 mRNA in rat aorta, but had
      little effect on the other tested tissues. The maximum increase in HSP70 mRNA
      level in the aorta was observed at 0.5-1 hr after the stress, and then it
      declined. Moreover, this stress also increased the level of HSP70 protein in the
      aorta, but had little effect on the other tested tissues. These results indicate
      that exposure of rats to mild psychological stress results in the induction of
      HSP70, especially in the blood vessels.

PMID- 9593225
TI  - Effects of F-1394, an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on
      ACAT activity in HepG2 cells and on hepatic secretion of lipids in Triton WR-1339
      induced hyperlipidemic rats: possible role of hepatic ACAT in very low density
      lipoprotein secretion.
AB  - We examined the inhibitory potency of F-1394 ((1S,2S)-2-[3-(2,2-dimethylpropyl)-3
      nonylureido]cyclohexane -1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1,3-dioxane-4
      carbonyl)amino]propionate), an acyl-CoA:cholesterol acyltransferase (ACAT)
      inhibitor, on ACAT activity and its hypolipidemic effect. F-1394 inhibited whole
      cell ACAT activity in HepG2 cells with an IC50 value of 42 nM. The potency of F
      1394 was greater than that of the five other ACAT inhibitors tested (YM-17E, CI
      976, 57-118, CL-277,082 and DL-melinamide). In rats made hyperlipidemic by Triton
      WR-1339, F-1394 caused a reduction in the hepatic secretion rate of cholesterol.
      These data suggest that inhibition of hepatic ACAT activity helps to reduce very
      low density lipoprotein secretion from the liver into the circulation.

PMID- 9593226
TI  - Bifemelane protects cultured cortical neurons against N-methyl-D-aspartate
      receptor-mediated glutamate cytotoxicity.
AB  - This study was performed to examine the neuroprotective action of bifemelane
      against glutamate cytotoxicity in cultured cortical neurons obtained from fetal
      rats. Cell viability was markedly reduced by a brief exposure to glutamate.
      Glutamate cytotoxicity was reduced by exposing cultures to bifemelane at
      concentrations of 1-10 microM for 24 hr prior to glutamate exposure. In contrast,
      glutamate cytotoxicity was not affected by adding bifemelane to the glutamate
      containing-medium without pretreatment. Bifemelane did not affect N-methyl-D
      aspartate (NMDA)-induced currents, although the higher concentration (100 microM)
      of the drug reduced them. These findings suggest that bifemelane protects against
      glutamate neurotoxicity without affecting NMDA receptors.

PMID- 9593227
TI  - Effect of tazarotene, an acetylenic retinoid, on human dermal fibroblast.
AB  - The inhibitory effect of tazarotene, an acetylenic retinoid, on human dermal
      fibroblast in vitro was compared to that of all-trans-retinoic acid. The
      proliferation of fibroblasts was inhibited by both retinoids at the concentration
      of 1 microM after 5 days of culture. Synthesis of DNA and collagen was inhibited
      by both retinoids concentration-dependently up to 10 microM, although tazarotene
      was weaker in the inhibition of collagen synthesis. These results suggest the
      possible usefulness of tazarotene in the treatment of fibrotic diseases.

PMID- 9593228
TI  - Repeated injections of nicergoline increase the nerve growth factor level in the
      aged rat brain.
AB  - We studied whether nicergoline, clinically active in chronic cerebrovascular
      insufficiency, influences nerve growth factor (NGF) levels in the rat brain. In
      young Fischer rats, repeated intraperitoneal injections of nicergoline (0.3 and
      1.0 mg/kg body weight) did not show any effects on frontal NGF contents
      determined by a highly sensitive enzyme immunoassay. In aged rats, 22-month-old,
      however, repeated injections of nicergoline (1.0 mg/kg body weight) induced a
      significant increase in the NGF level in the frontal region.

PMID- 9593229
TI  - Antiepileptic drug-induced worsening of seizures in children.
AB  - Antiepileptic drugs (AEDs) may aggravate pre-existing seizures and trigger new
      seizure types. However, the extent and mechanisms of this problem are unclear,
      for several reasons. AED trials are not designed to detect worsening of seizures,
      severe childhood epilepsies may fluctuate in severity, and worsening of seizures
      may be over-hastily ascribed to the introduction of a new AED. Moreover, the
      seizure and the epilepsy type may have been incorrectly diagnosed. The problem is
      identification of true aggravation of epilepsy in the absence of overdosage or
      toxicity. This is a common and clinically important problem that concerns both
      established and newer AEDs, but the biologic mechanisms involved are unknown. An
      increase in seizure frequency due to overdosage has been reported with phenytoin
      but is rare with other AEDs. Paradoxical reaction has been reported with
      carbamazepine (CBZ), benzodiazepines, and vigabatrin (VGB). Exacerbation of
      seizures may also occur during AED-induced encephalopathy or hepatopathy. An
      inappropriate choice of the AED (i.e., a purely pharmacodynamic mechanism) can
      induce worsening when CBZ or VGB is used in absence and myoclonic seizures.
      Further research should determine whether seizure exacerbation is associated with
      the type of epilepsy or with the type of EEG abnormality. Recent evidence
      indicates that lamotrigine is inappropriate in severe myoclonic epilepsy. Some
      childhood epileptic encephalopathies have been affected by certain seizure
      worsening mechanisms. Whether this is due to a predisposition in specific
      syndromes or to an increased risk for adverse effects in patients undergoing
      multiple AED manipulations is unclear. Furthermore, some syndromes are not the
      sum of accompanying seizure types but have unique neurobiology.

PMID- 9593230
TI  - Aggravation of generalized epilepsies.
AB  - Generalized epilepsies are treatable with a number of antiepileptic drugs (AEDs)
      that are effective in different seizure types and epilepsy syndromes. The
      mechanisms of action of these AEDs are incompletely understood but include
      inhibition of low-threshold calcium currents and of voltage-gated sodium channels
      and facilitation of GABA(A) receptor currents. The mechanisms of aggravation are
      also unknown but could include elevation of brain GABA, blockade of voltage-gated
      sodium channels, and idiosyncratic toxicity reactions. Anecdotal reports suggest
      that aggravation of generalized epilepsy can occur with virtually all AEDs. The
      best-documented examples are aggravation of absences by carbamazepine and
      aggravation of symptomatic generalized epilepsies by vigabatrin. Therefore, the
      physician must be constantly aware of the problem of aggravation of seizures by
      AEDs. With careful diagnosis of the epileptic syndrome and an awareness of the
      problem, aggravation of seizures can be minimized.

PMID- 9593231
TI  - Aggravation of focal epileptic seizures by antiepileptic drugs.
AB  - Aggravation of focal epileptic seizures in adults is common after the
      antiepileptic drug (AED) therapy is initiated. Sometimes aggravation is mimicked
      by clustering of the seizures. Therefore, it is always necessary to analyze the
      patient's history and therapy carefully before drawing any conclusions. It is
      likely that a paradoxical aggravation of epileptic seizures can be attributed to
      the given AED and is sometimes, but only rarely, due to drug interactions.

PMID- 9593232
TI  - An economic appraisal of carbamazepine, lamotrigine, phenytoin and valproate as
      initial treatment in adults with newly diagnosed epilepsy.
AB  - We undertook an economic appraisal of four drugs used in monotherapy during the
      first 2 years of treatment for newly diagnosed patients with epilepsy:
      carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), and valproate (VPA). We
      adopted the cost-minimization model because, although no single trial compares
      all four drugs directly, the clinical trials comparing two or more of these drugs
      in newly diagnosed cases show no significant difference in efficacy between the
      drugs in terms of seizure frequency. Considered in the cost analyses were
      frequency of side effects, retention rates, medical consultations, inpatient and
      accident and emergency costs, laboratory investigations, and drug changes. A
      Delphi panel provided the treatment pathways, including frequency of clinical
      consultations, second-line monotherapy, and side-effects management. A
      sensitivity analysis was performed, varying the assumptions on which the
      calculations were based. Analysis was completed for a prospective, intention-to
      treat perspective and also for those patients continuing the initial drug. The
      direct medical costs of 2-years therapy (intention-to-treat analysis) calculated
      for each trial were pound sterling 795-829 for CBZ, pound sterling 1,525-2,076
      for LTG, pound sterling 736-768 for PHT, and pound sterling 868-884 for VPA. A
      sensitivity analysis provided similar relative estimates. We found that LTG for
      newly diagnosed patients is significantly more expensive in direct health service
      costs incurred. This analysis incorporated seizure control, side effects, and
      tolerability. We recommend that a similar type of analysis be considered as part
      of all clinical trials of antiepileptic drugs in which efficacy of outcome is
      similar as a guide to assess optimal cost effectiveness.

PMID- 9593233
TI  - Summary. Aggravation of seizures by antiepileptic drugs: what to do in clinical
      practice.

PMID- 9593234
TI  - Preoperative irradiation affects functional results after surgery for rectal
      cancer: results from a randomized study.
AB  - PURPOSE: The Swedish Rectal Cancer Trial has unequivocally demonstrated that
      preoperative high-dose (5 x 5 Gy) radiotherapy reduces local failure rates and
      improves overall survival. This will have an impact on the primary treatment of
      rectal cancer. This study investigates the effect of preoperative high-dose
      radiotherapy on long-term bowel function in patients treated with anterior
      resection. METHODS: A questionnaire was answered by 92 percent (203/220) of
      patients who were included in the Swedish Rectal Cancer Trial and who were alive
      after a minimum of five years. Thirty-two patients were excluded, mainly because
      of postoperative stomas and dementia, which left 171 for analysis. RESULTS:
      Median bowel frequency per week was 20 in the irradiated group (n = 84) and 10 in
      the surgery-alone group (n = 87; P < 0.001). Incontinence for loose stools (P <
      0.001), urgency (P < 0.001), and emptying difficulties (P < 0.05) were all more
      common after irradiation. Sensory functions such as "discrimination between gas
      and stool" and "ability to safely release flatus" did not, however, differ
      between groups. Thirty percent of the irradiated group stated that they had an
      impaired social life because of bowel dysfunction, compared with 10 percent of
      the surgery-alone group (P < 0.01). CONCLUSIONS: The study indicates that high
      dose radiotherapy influences long-term bowel function, thus emphasizing the need
      for finding predictive factors for local recurrence to exclude patients with a
      very high probability for cure with surgery alone and to use optimized radiation
      techniques.

PMID- 9593235
TI  - Incidence of neoplastic polyps in the ileal pouch of patients with familial
      adenomatous polyposis after restorative proctocolectomy.
AB  - PURPOSE: Although adenomatous polyps and even adenocarcinomas have been found in
      the terminal ileum of patients with familial adenomatous polyposis, the
      prevalence of neoplastic changes in the pouches of patients who have undergone
      restorative proctocolectomy is unknown. The objective of this study was to
      determine the frequency of pelvic pouch neoplasia in familial adenomatous
      polyposis patients after restorative proctocolectomy. METHODS: Patients in a
      polyposis registry who had undergone restorative proctocolectomy were recruited.
      Demographic, surgical, pathologic, and endoscopic data were obtained from patient
      records. Video pouchoscopy was done after two enemas and representative biopsies
      were taken. RESULTS: Of 102 eligible patients, 26 (17 males and 9 females)
      participated. Median age at ileal pouch-anal anastomosis was 31 (range, 12-58)
      years. Median follow-up period was 66 (11-156) months. Adenomas were found in the
      pouch of 11 (42 percent) patients, in the terminal ileum above the pouch in 1
      patient, and in the anal canal of 4 patients. Among patients with pouch polyps,
      three patients had one lesion, three patients had two lesions, and five patients
      had more than ten lesions. The incidence of polyps increased steadily with time
      from restorative proctocolectomy. There was no relation between the incidence of
      pouch polyposis and the severity of colonic or duodenal disease. CONCLUSIONS:
      Proctocolectomy and ileal pouch-anal anastomosis is associated with a significant
      risk of pouch neoplasia in familial adenomatous polyposis patients. The severity
      of pouch adenomas was not related either to the severity of colonic or duodenal
      disease. The pelvic pouches of all patients with familial adenomatous polyposis
      who have undergone restorative proctocolectomy should be examined periodically.

PMID- 9593236
TI  - Indications for colonic J-pouch reconstruction after anterior resection for
      rectal cancer: determining the optimum level of anastomosis.
AB  - PURPOSE: Functional outcome after anterior resection for rectal cancer is
      improved by colonic J-pouch reconstruction compared with straight anastomosis.
      The indications for colonic J-pouch reconstruction have yet to be determined.
      Therefore, we attempted to determine the level at which J-pouch reconstruction
      provides an advantage over straight anastomosis. METHODS: A total of 48 patients
      who underwent 5-cm colonic J-pouch reconstruction (J-pouch group) and 80 patients
      who underwent straight anastomosis (straight group) underwent functional
      assessment one year postoperatively. RESULTS: The functional outcome in the J
      pouch group was significantly better than that in the straight group when the
      distance of the anastomosis from the anal verge was less than 8 cm. The
      difference was particularly obvious when the level of the anastomosis was below 4
      cm. However, functional outcome in the straight group when the anastomosis was
      between 9 and 12 cm from the anal verge was also satisfactory and did not differ
      from that in the J-pouch group when the anastomosis was between 5 and 8 cm from
      the anal verge. CONCLUSIONS: Colonic J-pouch reconstruction is indicated when the
      distance of anastomosis from the anal verge is less than 8 cm, and it is
      essential when the distance is less than 4 cm.

PMID- 9593238
TI  - Effect of perioperative blood transfusions on recurrence of colorectal cancer:
      meta-analysis stratified on risk factors.
AB  - PURPOSE: This study was undertaken to evaluate the influence of perioperative
      blood transfusions on colorectal cancer recurrence. METHODS: All articles
      published up to December 1996 in English (or with an English abstract) were
      retrieved, both using MEDLINE and scanning their references, to be considered for
      this meta-analysis. RESULTS: One hundred thirty-one articles were identified, and
      99 of them were excluded because they analyzed survival or mortality, were
      repetitive publications, or were reviews or letters. Thirty-two original studies
      (9 were prospective) on 11,071 patients were included for further analysis; 20
      showed a detrimental effect of perioperative blood transfusions. Nineteen
      articles used also multivariable techniques, and 11 found perioperative blood
      transfusions to be an independent prognostic factor. Pooled estimates of the
      effect of perioperative blood transfusions on colorectal cancer recurrence
      yielded an overall odds ratio of 1.68 (95 percent confidence interval, 1.54-1.83)
      and a rate difference of 0.13 (95 percent confidence interval, 0.09-0.17) against
      patients who received transfusions. Stratified meta-analyses also confirmed these
      findings when stratifying patients by site and stage of disease. The effect of
      perioperative blood transfusion was observed in a dose-related fashion,
      regardless of timing and type, although some heterogeneity was detected. Data on
      surgical techniques were not available for further analysis. CONCLUSIONS: A
      consistently detrimental association was discovered between the use of
      perioperative blood transfusion and colorectal cancer recurrence. Further studies
      are needed to confirm that blood transfusion has a causal association.

PMID- 9593237
TI  - Colon adenocarcinoma and B-16 melanoma grow larger following laparotomy vs.
      pneumoperitoneum in a murine model.
AB  - PURPOSE: Mouse mammary carcinoma tumors are established more easily and grow
      larger after sham laparotomy and open bowel resection than after CO2
      pneumoperitoneum and laparoscopic-assisted bowel resection. The purpose of this
      study was to determine whether similar differences in tumor growth would be found
      when sham laparotomy and pneumoperitoneum were compared for the colon-26 mouse
      adenocarcinoma and B-16 mouse melanoma tumor lines. METHODS: In all three
      studies, a high-dose injection of tumor cells was used, which resulted in tumors
      in almost all control mice. In Study 1, female BALB/C mice (n = 127) were
      injected intradermally in the dorsal skin with 10(6) colon-26 cells in a 0.1-ml
      volume before interventions. In Study 2, female C57 BL/6 mice (n = 140) were
      inoculated similarly with 10(6) B-16 melanoma cells. Study 2 consisted of three
      separate trials conducted on different days. Study 3 was performed because
      considerable differences in mean tumor size were observed in each of these
      trials. In Study 3, the B16 experiment was repeated with a larger n (n = 82) on a
      single day. In each study, after tumor cell injections, mice were randomly
      assigned to one of three groups: 1) anesthesia control (no procedure); 2) full
      laparotomy (4-cm midline incision x 20 minutes, staple closure); or 3) CO2
      pneumoperitoneum (4-6 mmHg X 20 minutes). Tumors were excised and weighed on
      postoperative day 12. RESULTS: In Studies 1 and 3, mean tumor sizes of the
      laparotomy groups were significantly larger than both the control group and
      pneumoperitoneum group lesions (P values by Student's t-test). In Study 2,
      laparotomy group tumors, although significantly larger than control group
      lesions, were not significantly larger than pneumoperitoneum group tumors. For
      all three studies, there was no significant difference between mean tumor sizes
      of the pneumoperitoneum and control groups. CONCLUSION: Both colon-26
      adenocarcinoma and B-16 melanoma tumors grow larger after laparotomy than after
      pneumoperitoneum in a murine model. The mechanism of these postoperative tumor
      growth differences remains to be elucidated.

PMID- 9593239
TI  - Postpartum fecal incontinence is more common in women with irritable bowel
      syndrome.
AB  - PURPOSE: Anal sphincter damage can occur during vaginal delivery and may lead to
      impairment of fecal continence. The aim of this study was to determine the
      influence of irritable bowel syndrome on symptoms of fecal incontinence following
      first vaginal delivery. METHODS: A prospective, observational study was performed
      before delivery, six weeks, and six months following delivery in primiparous
      women. A bowel function questionnaire was completed, and anal vector manometry,
      mucosal electrosensitivity, pudendal nerve terminal motor latency, and anal
      endosonography were performed. A total of 208 women were assessed before and
      after delivery, and 104 primigravid women were studied after delivery only. A
      total of 34 of 312 (11 percent) had an existing diagnosis of irritable bowel
      syndrome. RESULTS: The prevalence of abnormal manometry or endosonography was
      similar in women with and without irritable bowel syndrome. However, six weeks
      after delivery, women with irritable bowel syndrome had a higher incidence of
      defecatory urgency (64 percent) and loss of control of flatus (35 percent)
      compared with those without (urgency, 10 percent, P < 0.001; flatus, 13 percent,
      P = 0.007). The incidence of frank fecal incontinence was similar in the two
      groups. Women with IBS had increased mucosal sensitivity to electrical
      stimulation of the upper anal canal both before and after delivery. CONCLUSION:
      Women with IBS are more likely to experience subjective alteration of fecal
      continence postpartum compared with the healthy primigravid population, but they
      are not at increased risk of anal sphincter injury.

PMID- 9593240
TI  - Electrostimulation in fecal incontinence: relevance of the sphincteric compound
      muscle action potential.
AB  - PURPOSE: Continence scores and anal manometry are commonly used to assess the
      effect of electrostimulation in fecal incontinence. This study determined the
      increase of muscular compound potentials in electroneurography of the pudendal
      nerve after three months of electrostimulation treatment. PATIENTS AND METHODS:
      Thirty women were tested; their average age was 46.8 (standard deviation, 9.82)
      years. Electrostimulation was applied twice daily for 15 minutes in each case.
      RESULTS: Before treatment, amplitudes were, on average, 0.54 mV (standard
      deviation, 0.2). After three months of electrostimulation, the amplitudes had
      increased to 0.84 mV (standard deviation, 0.2). The continence score was improved
      from 8.73 to 7.1 points. CONCLUSION: We believe that by electrostimulation the
      atrophic muscle can be trained to stabilize the pelvic floor, thus increasing
      anal pressure and, thereby, creating a basis for adequate voluntary contraction.
      Electrostimulation is, therefore, especially suitable for functional deficits of
      the external anal sphincter (insufficient voluntary contractions because of
      atrophic muscle) without identifiable muscular lesion.

PMID- 9593241
TI  - Paradoxical high anal resting pressures in men with idiopathic fecal seepage.
AB  - PURPOSE: Fecal incontinence has been a matter of concern for many years, but
      seepage is poorly understood, especially in men. METHODS: We compared the results
      of anorectal physiologic tests in a group of 16 male patients who complained of
      fecal soiling but had no previous history of anorectal surgery or disease and had
      normal clinical examinations with findings of 16 normal male controls. Physical
      examination and proctosigmoidoscopy were normal in each patient. RESULTS: Maximum
      anal resting pressure (median interquartile range) was 136 (120-145) cm H2O in
      the "seepage" group and 104 (83-112) cm H2O in controls (P < 0.01). Inflation
      volumes at which patients and controls experienced rectal sensation were 45 (35
      80) and 90 (75-100) ml of air, respectively (P < 0.01). Maximum tolerated volumes
      in the rectum were 130 (85-180) ml of air in the seepage group and 190 (140-240)
      ml of air in controls (P < 0.01). Median length of the anal sphincter was 3.75
      (3.5-4) cm in patients and 3 (3-3.5) cm in controls (P < 0.01). Maximum squeeze
      pressures, sensation in the anal canal, and sphincter relaxation in response to
      rectal distention were similar in the two groups. CONCLUSION: Male patients with
      "idiopathic" fecal seepage have a long anal sphincter with abnormally high
      resting tone.

PMID- 9593242
TI  - Anal endosonographic evaluation after closed lateral subcutaneous sphincterotomy.
AB  - PURPOSE: The present study was undertaken to evaluate anal endosonographic
      results of the transverse and longitudinal extent of internal anal sphincter
      division after closed lateral subcutaneous sphincterotomy and its relationship to
      outcome with respect to anal fissure recurrence and postoperative anal
      incontinence. METHODS: Ten patients selected for symptomatic anal fissure
      recurrence (mean follow-up, 10.9 months) and 41 asymptomatic control patients
      (mean follow-up, 15.5 months) were reviewed by anal endosonography after closed
      lateral subcutaneous sphincterotomy. Clinical evaluation was focused on anal
      fissure recurrence and postoperative anal incontinence. The anal endosonographic
      study involves serial radial images of the distal, proximal, and midanal canal.
      RESULTS: In 32 patients in whom a complete internal sphincter defect was
      identified, 31 (75.6 percent) were from the control group and only 1 patient (10
      percent) was from the recurrence group (P < 0.001). In 19 patients, an incomplete
      internal sphincter defect was identified; 10 (24.4 percent) were from the control
      group (residual median size, 1.8 mm; contralateral, 2.5 mm) and 9 patients (90
      percent) were from the recurrence group (P = 0.001; residual median size, 1.4 mm;
      contralateral, 2.2 mm). Ten patients (19.6 percent) were incontinent for gas and
      three patients (5.9 percent) for liquid feces, without significant differences
      between groups. CONCLUSIONS: Anal endosonography is a useful method for
      evaluating the anatomic effectiveness of closed lateral subcutaneous
      sphincterotomy. An incomplete sphincterotomy is associated with significant
      symptomatic anal fissure recurrence.

PMID- 9593243
TI  - Is rectal intussusception a cause of idiopathic incontinence?
AB  - PURPOSE: The cause of rectal intussusception in patients primarily dominated by
      symptoms of anal incontinence has not been fully elucidated, especially for
      patients with idiopathic incontinence. METHODS: Between 1991 and 1996, 51
      patients referred with a diagnosis of idiopathic incontinence were prospectively
      evaluated by standard questionnaire, clinical examination, defecography, and anal
      manometry. Fourteen female patients were identified with rectal intussusception
      and were treated by transabdominal rectopexy. Postoperatively, clinical
      assessment and anal manometry were performed at regular intervals. RESULTS:
      Continence was improved after rectopexy (P < 0.01). The postoperative increases
      in the anal resting pressure, maximum squeeze pressure, and maximum tolerated
      volume were not statistically significant. CONCLUSIONS: Rectopexy improved anal
      incontinence in patients with rectal intussusception. The cause of rectal
      intussusception in anal incontinence could not be explained by functional
      improvement of the internal anal sphincter tone or an increase in the maximum
      tolerated volume. Rectal intussusception may be a cause of idiopathic
      incontinence in patients; however, larger prospective studies are required to
      support this concept.

PMID- 9593245
TI  - Complicated diverticulitis following renal transplantation.
AB  - PURPOSE: Colonic perforations in renal transplant recipients have historically
      been associated with mortality rates as high as 50 to 100 percent. However, these
      previous series generally predate the use of cyclosporine-based immunosuppressive
      protocols. METHODS: We retrospectively reviewed all patients who had undergone
      renal transplant from our institution and who developed complicated
      diverticulitis. Complicated diverticulitis was defined as diverticulitis
      involving free perforation, abscess, phlegmon, or fistula. Factors analyzed
      included the time interval since transplantation, use of cyclosporine, living
      related vs. cadaveric donor, cause of renal failure, and presenting signs and
      symptoms. RESULTS: Between August 1969 and September 1996, 1,211 kidney
      transplants were performed in 1,137 patients. The first 388 patients (1969-1984)
      received prednisone and azathioprine, with cyclosporine added to the
      immunosuppressive regimen for the subsequent 823 recipients (1984-1996). Thirteen
      (1.1 percent) patients had episodes of complicated diverticulitis, occurring from
      25 days to 14 years after transplant; all required surgical therapy. Clinical
      presentation was highly variable, ranging from asymptomatic pneumoperitoneum (2
      patients) to generalized peritonitis. There was one perioperative mortality (7.7
      percent). Patients with polycystic kidney disease as the cause of renal failure
      had a significantly higher rate of complicated diverticulitis. Specifically,
      patients with polycystic kidney disease (9 percent of the total transplant
      population) accounted for 46 percent of the cases of diverticulitis (P < 0.001,
      Fisher's exact probability test). Neither treatment with cyclosporine nor donor
      source had a significant effect on the rate of diverticular complications (P =
      0.36 and P = 0.99, respectively, Fisher's exact probability test). CONCLUSION:
      Complicated diverticulitis following renal transplantation is rare, and the
      clinical presentation may be atypical in the immunosuppressed transplant
      recipient. Patients with polycystic kidney disease experience a significantly
      higher rate of complicated diverticulitis than do other transplant patients and,
      therefore, warrant aggressive diagnostic evaluation of even vague abdominal
      symptoms. In addition, pretransplant screening and prophylactic sigmoid resection
      in this high-risk population deserve consideration and further study.

PMID- 9593244
TI  - Perianal manifestations of human immunodeficiency virus infection: experience
      with 260 patients.
AB  - PURPOSE: Individuals infected with the human immunodeficiency virus often have
      disorders affecting the anorectum. These disorders may be complex and difficult
      to treat. We reported our early experience with 40 human immunodeficiency virus
      positive patients with perianal disorders in 1990. We now present our series of
      260 consecutive human immunodeficiency virus-positive patients with perianal
      disorders who underwent evaluation between 1989 and 1996 to examine the
      distribution of disorders, their treatments, and outcomes. METHOD: Patients were
      identified at initial presentation and followed prospectively. RESULTS: Two
      hundred forty-nine (96 percent) of 260 patients were male, with an average age of
      34.9 (range, 19-58) years. Average duration of human immunodeficiency virus
      positivity was 5 years, 5 months, with a maximum of 11 years, 5 months. Median
      CD4 count was 175 (range, 2-1,100) cells/mm3. Only 89 (34 percent) patients
      satisfied the criteria of the Centers for Disease Control and Prevention's for
      acquired immunodeficiency syndrome at presentation. The most frequent major
      presenting symptoms were anorectal pain (55 percent), a mass (19 percent), and
      blood in the stool (16 percent). Risk factors included homosexuality (75 percent)
      and a prior history of sexually transmitted disease (45 percent). Forty different
      perianal disorders were identified, which were categorized as benign
      noninfectious (18), infectious (14), neoplastic (6), and septic (2). The most
      common disorders were condyloma (42 percent), fistula (34 percent), fissure (32
      percent), and abscess (25 percent). Neoplasms were present in 19 patients (7
      percent). One hundred seventy-one patients (66 percent) had more than one
      disorder, with an average of 2.9 disorders among these patients. Four hundred
      eighty-five procedures were performed on 178 patients (2.7/patient), with no
      mortalities and a 2 percent complication rate. Thirty-one patients (12 percent)
      died during the course of follow-up, but anorectal disease was the cause of death
      in only two patients. CONCLUSIONS: Perianal manifestations of human
      immunodeficiency virus infection are common, often multiple, and varied. Patients
      with perianal disorders seek treatment throughout the course of the human
      immunodeficiency virus infection, and a perianal condition may be this disease's
      initial manifestation. Although recurrence is common and healing delayed,
      improved overall management of human immunodeficiency virus infection and a
      healthier human immunodeficiency virus-positive patient population have improved
      the outcome of surgical intervention in human immunodeficiency virus-infected
      patients with perianal disorders.

PMID- 9593246
TI  - Cytomegalovirus enteritis: a highly lethal condition requiring early detection
      and intervention.
AB  - Cytomegalovirus infection causing symptomatic enteritis is most usually
      associated with immunosuppressed transplant patients or patients positive for
      human immunodeficiency virus. Most reports studying this illness are small and do
      not clearly define the risk factors or mortality rates. METHODS: The present
      study retrospectively reviewed the charts of 67 patients with biopsy-proven
      cytomegalovirus enteritis (esophageal, gastric, small bowel, and colonic) to
      define and to investigate factors that influence survival. Patients were
      classified into four groups based on underlying medical condition: 1) patients
      positive for human immunodeficiency virus; 2) transplant patients receiving
      immunosuppressive medications; 3) immunosuppressed nontransplant patients; and 4)
      otherwise healthy individuals. Mortality rates based on underlying medical
      condition, location of intestinal cytomegalovirus infection, cytomegalovirus
      therapy, age, and average days to institution of treatment were defined and
      statistically assessed. RESULTS: Mortality was significantly greater in the
      normal patient group (80 percent) than in the transplant (21 percent), other
      immunosuppressed (44 percent), or human immunodeficiency virus-positive (75
      percent) groups (P = 0.0006, Cochran-Mantel-Haenszel statistics). There was no
      difference in mortality based on intestinal location of disease or treatment
      modality (surgery, medical therapy, or both). Cohorts of patients older than 65
      years had a statistically higher mortality rate vs. those younger than 65 years
      old (68 vs. 38 percent; P = 0.05, Cochran-Mantel-Haenszel statistics).
      Statistically increased mortality was also associated with increased time from
      hospital admission to institution of cytomegalovirus treatment, whether therapy
      was medication alone or medication and surgery (P < 0.05, exact Wilcoxon's test).
      CONCLUSIONS: 1) Lethal cytomegalovirus enteritis can arise in patient populations
      not typically identified as being at risk for this disorder, including normal
      individuals. 2) Mortality in cytomegalovirus enteritis is adversely associated
      with age older than 65 years and increased time to institution of therapy but is
      not affected by anatomic site of infection or particular form of treatment.
      Paradoxically, in this study, normal patients had the highest mortality, which we
      attribute to a low index of suspicion and relatively late institution of therapy.

PMID- 9593247
TI  - Perianal injection of polydimethylsiloxane (Bioplastique implants) paste in the
      treatment of soiling: pilot study in rats to determine migratory tendency and
      locoregional reaction.
AB  - Not much is known about the specific pathophysiologic mechanisms of soiling.
      Although the causes of soiling may vary, it is mostly associated with anorectal
      disorders that can deform the contour of the anus and anal canal. In most cases,
      this disorder can be treated successfully by medical or surgical therapy. If this
      appropriate treatment is not available or fails, reconstruction of the contour
      deformity of the anus by perianal (submucosal) injection of soft tissue bulking
      agents may be successful. PURPOSE: The main purpose of this pilot study was to
      evaluate locoregional reaction and distant migration after local perianal
      injection of solid polydimethylsiloxane elastomer particles (Bioplastique
      implants). METHODS: Twelve Lewis rats received a local perianal injection of
      Bioplastique implants. Six of them received an additional perianal injection of
      gentamicin. Six weeks after injection, the rats were euthanized. RESULTS:
      Microscopically, the local tissue reaction was that of a quiescent foreign body
      reacting with encapsulation. Microscopic examinations could not reveal any
      migration to locoregional lymph nodes, liver, spleen, lungs, or brain.
      CONCLUSION: We conclude that, because of minimum local reaction and lack of
      evidence of distant migration, polydimethylsiloxane elastomer particle paste
      (Bioplastique implants) seems to be a potentially safe substance for local
      perianal injection.

PMID- 9593248
TI  - Hand-assisted laparoscopic sigmoidectomy for diverticulitis.
AB  - BACKGROUND: Sigmoid colectomy for diverticular disease, a routine procedure when
      performed using standard open methods, can prove much more challenging using
      minimum access techniques. Hand-assisted laparoscopic colectomy is a new
      technique that reportedly has a minimum learning curve, yet retains the benefits
      of a laparoscopic procedure. The purpose of this study was to perform and then
      prospectively to evaluate the outcome of this procedure on patients needing
      elective sigmoidectomy for diverticular disease. METHODS: Hand-assisted
      laparoscopic sigmoidectomy was performed on all patients undergoing elective
      sigmoidectomy for diverticular disease between January 18, 1996, and November 21,
      1996. RESULTS: The study group consisted of six men and three women. Age averaged
      50.8 (range, 39-66) years, weight averaged 183 (range, 150-224) pounds, and
      operation time averaged 3 hours and 42 minutes (range, 3-5 hours). No cases were
      converted to open methods. There were two minor postoperative complications
      (bleeding from the staple line, 1 patient; urinary retention, 1 patient; 22
      percent). Resumption of flatus (which was the indication to start the patient on
      an oral diet) occurred between one and three (average, 1.44) days
      postoperatively. Patients were discharged from the hospital between one and three
      (average, 2.1) days postoperatively. Primary surgeon responsibility was
      distributed among four different surgeons, of which only the lead author
      previously had performed laparoscopic colectomy at this institution. CONCLUSIONS:
      Hand-assisted laparoscopic sigmoidectomy is a procedure that has a minimum
      learning curve, yet retains the benefits of a laparoscopic procedure.

PMID- 9593249
TI  - Aggressive bowel preparation does not enhance bacterial translocation, provided
      the mucosal barrier is not disrupted: a prospective, randomized study.
AB  - PURPOSE: Prospective, randomized studies have shown that bowel preparation may
      adversely affect infectious complications following colonic resections. However,
      very little is known about the effects of bacterial translocation on these
      infectious complications. The aim of this prospective, randomized study was to
      assess the effects of bowel preparation on bacterial translocation. METHODS: A
      total of 82 consecutive patients undergoing elective abdominal operations were
      randomly assigned to four groups: control (I; n = 20), mechanical (II; n = 21),
      mechanical plus oral metronidazole (III; n = 20), and polyethylene glycol
      preparation (IV; n = 21). Patients with intra-abdominal infection, those
      receiving preoperative antibiotics for any reason, and those having lower
      gastrointestinal tract disease were excluded from the study. Peritoneal swab,
      ileocecal and pericolic mesenteric lymph nodes, liver wedge biopsy, portal venous
      blood, and peripheral blood samples were taken for culture. Patients were
      followed up for postoperative infectious complications. Groups were matched
      according to age, gender, body surface area, and Acute Physiology and Chronic
      Health Evaluation II scores. RESULTS: Bacterial translocation was identified by a
      positive culture in one patient in Group I, two in Group II, one in Group III,
      and three in Group IV, respectively. Differences in number of positive cultures
      among the groups were not statistically significant. Nine patients had major
      infectious complications. Only two had bacterial translocation, and the same
      micro-organisms grew in both patients, in one at the wound site and in the other
      at the cyst abscess. CONCLUSION: This study demonstrated that mechanical bowel
      preparation does not enhance the spontaneous occurrence of bacterial
      translocation in patients without any clinical signs of lower gastrointestinal
      tract disease.

PMID- 9593250
TI  - Beneficial effect of Iloprost on impaired colonic anastomotic healing induced by
      intraperitoneal 5-fluorouracil infusion.
AB  - PURPOSE: 5-Fluorouracil is the most effective chemotherapeutic agent in the
      management of patients with systemic colorectal cancer. Studies in recent years
      discussed the gradually increasing benefits of 5-fluorouracil within adjuvant
      chemotherapy protocols after complete surgical resections. However, many studies
      also have demonstrated that 5-fluorouracil impairs wound-healing on colonic
      anastomoses. METHODS: In our experimental study, we examined the influence of
      intraperitoneal 5-fluorouracil on healing of colonic anastomoses and, also,
      attempted to discover whether Iloprost (PGI2 analog, a potent vasodilator with
      confirmed cytoprotectivity and inhibitor of thrombocyte aggregation) counteracts
      impaired wound-healing induced by 5-fluorouracil. A total of 80 Wistar-Albino
      male rats were separated into four groups. From the day of the operation, Group A
      received intraperitoneal saline solution, Group B received 20 mg/kg 5
      fluorouracil intraperitoneally, Group C received 20 mg/kg 5-fluorouracil plus 2
      microg/kg Iloprost intraperitoneally, and Group D received 2 microg/kg Iloprost
      intraperitoneally. Each group was divided into two subgroups, and both subgroups
      were killed on the third and seventh postoperative days, respectively. The
      subjects were measured for anastomose bursting pressures and tissue
      hydroxyproline levels, and wound-healing was evaluated histopathologically.
      Statistical evaluations among each group were made with Student's t-test and
      Pearson's chi-squared tests. RESULTS: Iloprost had an accelerating effect on
      normal colonic anastomose wound-healing histopathologically, had no significant
      difference on bursting pressures and hydroxyproline levels, and significantly
      improved the impaired healing effect of 5-fluorouracil. CONCLUSIONS: Our study
      showed a positive effect of Iloprost on the healing of colon anastomosis and,
      more importantly, if wound-healing is impaired by a chemotherapeutic agent,
      Iloprost counteracts and reverses the effect. [Key words: 5-Fluorouracil; Healing
      of colon anastomoses; Iloprost

PMID- 9593252
TI  - Surgical management of a long efferent loop after J-pouch ileoanal
      reconstruction.
AB  - PURPOSE: To demonstrate a simple and effective repair of a poorly constructed
      ileal J-pouch with an extensive long efferent limb. METHOD: A retrospective case
      review was performed. RESULTS: The surgical procedure described preserves
      additional ileum and enlarges the ileal reservoir. The procedure succeeded in
      resolving the patient's complaints of partial obstruction, weight loss, and
      increased stool frequency. At five-month follow-up, the patient was doing well
      with three to six stools daily. Evaluation of the new ileal J-pouch showed no
      signs of inflammation, and the pouch size measured more than 20 cm compared with
      12 cm preoperatively. CONCLUSIONS: Repair of a long efferent limb by this simple
      stapling technique is feasible, simple, and effective, with an excellent clinical
      result. It preserves valuable small intestine and enlarges the capacity of the
      reservoir, leading to better functional outcome.

PMID- 9593251
TI  - Small spot sign of rectal carcinoma by endorectal ultrasonography: histologic
      relation and clinical impact on postoperative recurrence.
AB  - PURPOSE: We observed small spots at the margin of rectal carcinomas on endorectal
      ultrasonography. Our aim was to study the relationship between ultrasonographic
      evidence of these spots and histologic characteristics of disease and
      postoperative recurrence. PATIENTS AND METHODS: The study group comprised 55
      patients, 36 men and 19 women, with rectal carcinoma as confirmed by biopsy. The
      patients were followed up at three-month intervals for six months to three years
      and six months after the operation. Endorectal ultrasonography was performed in
      the usual manner. Surgically resected specimens were stained with hematoxylin and
      eosin and histologically examined. Vessel invasion was graded from 0 (not
      invasive) to 3 (most invasive). RESULTS: Among the 55 patients studied, 3 had
      Stage T2,N0,M0 rectal carcinomas and 35 had Stage T3,N0,M0 carcinomas, 5 (14.3
      percent) of whom had echographic evidence of small spots. Thirteen patients had
      Stage T3,N1/2,M0 carcinomas, comprising 12 (92.3 percent) with small spots, and
      four patients had T3,N1/2,M1 carcinomas, all with small spots. Vessel invasion of
      Grade 2 or higher was observed around the carcinomas in 20 of 21 patients who had
      small spots. Ten of 13 patients with many spots at the margin of the carcinoma (a
      spot grade of ++) histologically had marked venous or lymphatic invasion (an
      invasion Grade 3). The presence of small spots was closely associated with
      massive venous or lymphatic invasion (a vessel invasion grade of 2 or more). Four
      patients had synchronous liver metastases, and small spots were found in all
      four. Distant metastases and local recurrence were found in 11 of 21 patients
      with small spots. We found no recurrence in any patient without small spots on
      endorectal ultrasonography. CONCLUSIONS: Small spots indicate the presence of
      massive venous or lymphatic invasion and a high risk of postoperative recurrence.

PMID- 9593253
TI  - Rectal neovagina: Simonsen's technique for large rectovaginal fistula repair.
AB  - Rectovaginal fistulas are difficult to manage and cause significant morbidity. A
      new technique for large rectovaginal fistula repair is presented; it is based on
      the creation of a neovagina associated with an established abdominal pull-through
      operation. This technique has been used since 1970 in selected cases, with very
      little morbidity and no operative mortality.

PMID- 9593254
TI  - Mucosal ischemia caused by desmoid tumors in patients with familial adenomatous
      polyposis: report of four cases.
AB  - PURPOSE: The study contained herein was undertaken to demonstrate that mesenteric
      desmoid tumors can cause significant symptoms other than by a mass effect and
      that surgery can be effective in treating these symptoms. METHODS: The medical
      records of patients with intra-abdominal desmoid disease in the David G. Jagelman
      Inherited Colorectal Cancer Registry were reviewed. Four cases are described in
      which intramesenteric desmoid tumors adjacent to the bowel caused mucosal
      ischemia in patients with familial adenomatous polyposis. RESULTS: In one patient
      with an ileorectal anastomosis, this was manifest by multiple small-bowel
      strictures and treated by multiple strictureplasties. The other three patients
      had ileal pouches and presented with bleeding and pain from mucosal ulceration.
      All pouches needed to be removed. CONCLUSION: Intra-abdominal desmoid tumors may
      cause problems other than by mass effect. Patients with familial adenomatous
      polyposis and symptoms suggestive of desmoid disease but with no detectable mass
      should not be denied surgery.

PMID- 9593255
TI  - Retroperitoneal fibrosis mimicking a rectal tumor: report of a case.
AB  - PURPOSE: The study contained herein was undertaken to report an original case of
      retroperitoneal fibrosis that resembled a rectal tumor both symptomatically and
      radiologically. METHOD: Reported is a case of retrorectal fibrosis with a brief
      literature review of the topic. RESULT: Although many forms of retroperitoneal
      fibrosis have been reported, extension below the pelvic rim is very unusual.
      Compression of the rectum and right ureter, with constipation as a chief
      complaint, made this case presentation unusual. Although computerized tomographic
      findings and needle biopsies supported the diagnosis of retroperitoneal fibrosis,
      an exploratory laparotomy was necessary to rule out a malignancy and to release
      the ureter. CONCLUSION: A fibrotic mass involving the retrorectal region may
      mimic a rectal tumor. To reach a final diagnosis, an exploratory laparotomy may
      be necessary, despite sophisticated evaluation techniques, because it is
      difficult to differentiate whether the mass is malignant.

PMID- 9593256
TI  - Treatment of proctalgia fugax with topical nitroglycerin: report of a case.
AB  - PURPOSE: We report a single case of proctalgia fugax that responded to 0.3
      percent nitroglycerin ointment. METHODS: Case report. RESULTS: A single case of
      proctalgia fugax responded to topical application of 0.3 percent nitro glycerin
      ointment with no significant side effects. CONCLUSIONS: Nitroglycerin ointment is
      a newly described treatment for several painful anal conditions. We describe a
      single case of levator spasm or proctalgia fugax responding to topical
      application of nitroglycerin. This is only a single case report, and conclusive
      evidence awaits completion of a controlled clinical trial.

PMID- 9593257
TI  - Outcome analysis after interventions for rectal cancer.

PMID- 9593258
TI  - Biofeedback for constipation?

PMID- 9593259
TI  - Role of the adapter protein CRKL in signal transduction of normal hematopoietic
      and BCR/ABL-transformed cells.
AB  - CRKL is a 39 kDa adapter protein, originally cloned in proximity to the BCR gene
      on chromosome 22, which has a key regulatory role in hematopoietic cells. CRKL
      has one SH2 and two SH3 domains, with 60% homology to CRK II. CRKL is a prominent
      substrate of the BCR/ABL oncoprotein in chronic myelogenous leukemia and binds to
      both BCR/ABL and c-ABL. CRKL has been shown to be tryosine phosphorylated in
      response to normal hematopoietic growth factor receptor signaling with ligands
      such as thrombopoietin, erythropoietin or steel factor. Additionally, CRKL is
      involved in signaling initiated by crosslinking of beta integrins, and B cell or
      T cell receptors. Structurally, the amino-terminal SH3 domain of CRKL has been
      shown to bind proteins such as C3G, SOS, PI3-K, c-ABL or BCR/ABL. The SH2 domain
      of CRKL can bind to tyrosine phosphorylated proteins such as CBL, HEF1, CAS or
      paxillin. This review summarizes the current knowledge on the function of this
      unique adapter protein in normal hematopoietic and leukemic cell signaling.

PMID- 9593261
TI  - The role of intensive AML-specific therapy in treatment of children with RAEB and
      RAEB-t.
AB  - To determine the role of intensive chemotherapy and allogeneic bone marrow
      transplantation (BMT) in treatment of refractory anemia with excess of blasts
      (RAEB) or RAEB-t (in transformation), the outcome of 37 consecutive children, 12
      with RAEB and 25 with RAEB-t, diagnosed between 1985 and 1995 was analyzed.
      Fourteen patients received intensive chemotherapy according to the AML-BFM
      protocols 83, 87, or 93 (group 1). Seven patients were treated less intensively
      with the 6-week consolidation phase as induction (group 2). Allogeneic BMT was
      performed in 10 children of group 1 and 2 after, and in eight (group 3) without
      prior chemotherapy. Eight children received minimal or no chemotherapy (group 4).
      Of 21 children (groups 1 and 2) 17 (81%) achieved complete or partial remission
      after chemotherapy, 12 of them (10 of group 1) remained in remission, eight after
      BMT. Five-year survival in 29 children treated intensively (groups 1-3) was 46%,
      SE 12%. Two of the other eight children (group 4) remained alive, one after
      spontaneous remission. Outcome after BMT was related to the blast count in the
      bone marrow prior to BMT. None of 10 children (including two with minimal or no
      chemotherapy) with < or = 12% blasts before BMT relapsed, in contrast to five of
      eight patients with a higher blast count (P log rank 0.02). We conclude that a
      substantial number of children with RAEB or RAEB-t can achieve remission with
      intensive AML-specific chemotherapy. In patients responding to intensive
      chemotherapy an increase in long-term survival after allogeneic BMT can be
      expected.

PMID- 9593260
TI  - Down's syndrome in childhood acute lymphoblastic leukemia: clinical
      characteristics and treatment outcome in four consecutive BFM trials. Berlin
      Frankfurt-Munster Group.
AB  - Clinical characteristics, treatment response and outcome were evaluated in
      children with Down's syndrome (DS) and acute lymphoblastic leukemia (ALL) as
      compared to other children with ALL (NDS). Sixty-one DS and 4049 NDS patients,
      receiving intensive antileukemic treatment during four consecutive trials (ALL
      BFM 81, 83, 86 and 90) of the Berlin-Frankfurt-Munster Group (BFM), were
      retrospectively analyzed. DS and NDS children did not differ with respect to sex,
      leukocyte count, CNS leukemia and cytogenetic translocations. The DS cohort was
      slightly older (P=0.04), presented predominantly with the common while lacking
      the T immunophenotype (P=0.005), had a lower frequency of hyperdiploidy (P=0.004)
      and tended to have a better initial steroid response (P=0.057). Therapy
      associated morbidity especially during high-dose methotrexate and a subsequent
      need for treatment modification occurred in 43% of all DS patients. Event-free
      survival (EFS) was slightly worse in children with DS (58+/-8% vs 70+/-1%,
      P=0.14), mainly due to rather late bone marrow recurrences. However, EFS in DS
      patients was comparable to the NDS group once they either received treatment with
      no major modifications (65+9% vs 70+/-1%, P=0.66) or were <6 years of age,
      irrespectively of therapy modifications (73+/-9% vs 74+/-1%, P=0.7). Cox
      regression analysis revealed that DS was an adverse prognostic factor for
      patients having completed therapy (P=0.0107), but was not prognostic at diagnosis
      (P=0.103). Age > or = 6 years, suboptimal treatment and infectious problems
      contributed to the slight inferior EFS in children with ALL and Down's syndrome.
      Therefore, most of these patients can be successfully treated if receiving
      intensive antileukemic treatment with no major modifications, but they require
      more sophisticated management of toxicity.

PMID- 9593262
TI  - Hypersensitivity reactions to L-asparaginase do not impact on the remission
      duration of adults with acute lymphoblastic leukemia.
AB  - Among its multiple toxic effects, L-asparaginase induces allergic reactions that
      may reduce its biological effect. The impact of hypersensitivity reactions on the
      duration of leukemia-free survival (LFS) was assessed in adults with newly
      diagnosed acute lymphoblastic leukemia (ALL) receiving intensive multi-agent
      chemotherapy. In CALGB study 8811 (Blood 1995; 85: 2025-2037), 197 adults were
      scheduled to receive 14 doses of Escherichia coil L-asparaginase (6000 U/m2 SC)
      during 7 of the first 12 weeks of chemotherapy. No further L-asparaginase was
      given. Chemotherapy was given for 24 months. The median follow-up time has been
      5.7 years. Of the 141 patients who remained on study after 12 weeks, 82 (58%) had
      received all 14 planned doses; 38 (27%) had 12-13 L-asparaginase doses documented
      in their treatment record; 21 (15%) patients had received < or =11 doses due to a
      variety of toxic effects. The mean number of doses received prior to experiencing
      any hypersensitivity reaction was seven (range 1-11). Seven patients had mild
      hypersensitivity reactions, but all seven eventually received 12-14 doses of E.
      coil L-asparaginase. Twenty-one other patients had severe hypersensitivity
      reactions that required discontinuation of E. coil L-asparaginase; 20 of these
      patients were switched to Erwinia L-asparaginase to complete their treatment.
      Ultimately, 12 of these 20 patients received 14 doses of L-asparaginase in total,
      and six received 12-13 doses. Thus, only three of the 21 patients who had severe
      hypersensitivity reactions received < or =11 total L-asparaginase doses. Other L
      asparaginase-related complications included pancreatitis (15 patients),
      hypofibrinogenemia <100mg/dl (29 patients), and deep venous thrombosis or
      pulmonary embolism (eight patients); some of these patients had L-asparaginase
      discontinued after these complications. The estimates for LFS at 3 years were 55%
      (95% confidence interval, 44-65%) for the patients who received all 14 L
      asparaginase doses (median LFS, 5.1 years), 47% (95% CI, 33-62%) for those who
      received 12-13 doses, and 48% (95% CI, 29-67%) for those who received < or =11
      doses. There were no significant differences between these three groups in the
      length of LFS (P=0.68). LFS did not correlate with a history of severe
      hypersensitivity reaction (P=0.67). In general, E. coil L-asparaginase was well
      tolerated in these adult patients, and most patients received all of the planned
      therapy. Patients who had mild L-asparaginase hypersensitivity reactions and
      patients who switched to Erwinia L-asparaginase because of more severe allergic
      reactions did not have significantly shorter LFS than the remaining adults
      treated on this ALL protocol. The possibility that E. coli L-asparaginase is
      inactivated or destroyed in those individuals who have become hypersensitive to
      it becomes less important when allergic patients are secondarily treated with
      Erwinia L-asparaginase.

PMID- 9593263
TI  - Multilineage involvement of Philadelphia chromosome positive acute lymphoblastic
      leukemia.
AB  - Acute lymphocytic leukemia (ALL) is considered a clonal disease restricted to the
      lymphoid compartment. The Philadelphia chromosome (Ph) is found in a subset of
      ALL with poor prognosis. Here we present the largest series of Ph+ ALL analyzed
      for involvement of the myeloid compartment. For the first time at a single cell
      level the presence of Ph in lineages other than lymphoid is demonstrated.
      Granulocytes from nine patients diagnosed with BCR-ABL + ALL (eight Ph+, one Ph-)
      were purified using two layer density gradient separation. They were further
      identified by the morphology of DAPI-stained nuclei and studied for the presence
      of the Ph by fluorescence in situ hybridization (FISH) using a BCR-ABL dual-color
      probe. Ph was demonstrated in 30 to 93% of granulocytes in all patients. FISH
      identified major and minor BCR gene breakpoints (M-bcr and m-bcr). In one
      patient, with CD19+/34+/33-/2-/3-/7-/10- lymphoblasts, involvement of B cells
      (CD19+), T cells (CD3+), myeloid (CD13+), erythroid (glycophorin A+) cells was
      found by FISH following fluorescence-activated cell sorting (FACS). The diagnosis
      of ALL as opposed to lymphoblastic transformation of CML was established based on
      clinical and laboratory data including Western blot results demonstrating the
      presence of p190/m-bcr in five of the nine cases studied. Results suggest that
      Ph+ ALL originates from a pluripotent stem cell.

PMID- 9593264
TI  - Minimal residual disease after intensive induction therapy in childhood acute
      lymphoblastic leukemia predicts outcome.
AB  - We investigated the level of minimal residual disease (MRD) in 26 children with B
      lineage acute lymphoblastic leukemia (ALL) after intensive induction therapy. A
      quantitative semi-nested polymerase chain reaction (PCR) detecting the clone
      specific rearranged immunoglobulin heavy chain genes was developed to improve
      sensitivity and specificity of amplification. In all patients, one leukemic cell
      could be detected in a background of 10(5) normal blood mononuclear cells. All
      patients investigated were in complete remission at the end of induction therapy
      as evaluated by morphologic criteria. Nineteen patients (73%) had no detectable
      residual leukemic cells using the sensitive semi-nested PCR. Seven patients (27%)
      were PCR positive. Three had a low level (<2 x 10(-5) leukemic cells per bone
      marrow cell), while four patients had a high level (>2 x 10(5)) of detectable
      residual leukemic cells. All patients with low or undetectable levels of residual
      leukemia remained in complete remission at a median of 63 months from diagnosis
      (range 40-80 months), while all four patients with a high level of residual
      leukemia subsequently relapsed at a median of 21 months from diagnosis (range 13
      37 months). The patient groups with undetectable or low, and high level of MRD
      did not differ significantly in other clinical or genetic features with
      prognostic significance. We conclude that the level of MRD at the end of the
      intensive induction therapy period is predictive of outcome in childhood B
      lineage ALL. If confirmed by large prospective studies, the level of MRD might be
      useful in stratifying patients into high and low risk categories.

PMID- 9593265
TI  - IL-3 withdrawal activates a CrmA-insensitive poly(ADP-ribose) polymerase cleavage
      enzyme in factor-dependent myeloid progenitor cells.
AB  - Murine myeloid progenitor cells that are dependent on interleukin-3 (IL-3)
      undergo apoptosis when this essential cytokine is withdrawn. To determine whether
      IL-3 withdrawal leads to the activation of caspase proteases, known mediators of
      apoptosis, we studied proteolytic cleavage of the caspase substrate protein
      poly(ADP-ribose) polymerase (PARP) in two IL3-dependent myeloid progenitor cell
      lines, 32D and FDCP-1. We observed that IL-3 withdrawal leads to PARP cleavage in
      both cell lines, with complete cleavage occurring by 24 h after cytokine removal.
      The induced PARP cleavage activities were blocked by the caspase inhibitors z
      DEVD-fluoromethyl ketone (z-DEVD-FMK) and z-VAD-fluoromethyl ketone (z-VAD-FMK),
      or by overexpression in 32D cells of Bcl-2 or BCR/ABL. By contrast,
      overexpression in 32D cells of cowpox virus CrmA protein, an inhibitor of Fas
      mediated PARP cleavage, failed to inhibit PARP cleavage following IL-3
      withdrawal. CrmA also failed to block DNA fragmentation and loss of cell
      viability. We propose that a CrmA-insensitive caspase protease is activated in
      the IL-3-deprived myeloid precursors, and that activation of this protease may
      direct the cells on a path towards commitment to death.

PMID- 9593266
TI  - The myeloid zinc finger gene (MZF-1) delays retinoic acid-induced apoptosis and
      differentiation in myeloid leukemia cells.
AB  - The myeloid zinc finger gene, MZF-1, is a hematopoietic transcription factor
      expressed in developing myeloid cells. To characterize further the role of MZF-1
      in myelopoiesis, we used retroviral gene transduction to overexpress MZF-1 in HL
      60 cells to produce HL-60-MZF-1 cells. HL-60 cells respond to retinoic acid (RA)
      with growth inhibition, granulocytic differentiation and apoptosis. However, HL
      60-MZF-1 cells exposed to RA continue to proliferate in response to RA as
      evidenced by a higher percentage of cells in S phase, higher peak cell counts,
      and later peak cell counts. Morphologic differentiation of the RA-induced HL-60
      MZF-1 cells is delayed with half as many of the HL-60-MZF-1 cells compared to the
      wild-type HL-60 cells that are differentiated after 3 days of RA, although both
      cells types responded with 80-95% mature granulocytes after 6 days of RA.
      Apoptosis was delayed in the MZF-1 transduced cells as measured by
      internucleosomal DNA fragmentation patterns, the terminal transferase end
      labeling reaction (TUNEL), and quantitation of fragmented DNA by the
      diphenylamine reaction. Several markers of differentiation were identical in both
      HL-60 and HL-60-MZF-1 cells including CD11b, CD33, CD34, CD13, CD16 and CD14.
      However, following 6 days of RA, only half as many HL-60-MZF-1 cells expressed
      CD18 compared to the wild-type HL-60 cells. Expression of the bcl-2 proto
      oncogene transcript and protein was higher in the HL-60-MZF-1 cells compared to
      wild-type HL-60s and expression persisted for 5 days following RA in the HL-60
      MZF-1 cells compared to only 3 days in the parental HL-60 cells suggesting that
      bcl-2 may contribute to the inhibition of apoptosis. Overexpression of MZF-1 had
      no effect on PMA-induced monocyte/macrophage differentiation of HL-60 cells.
      Together these findings indicate that MZF-1 can stimulate cell proliferation and
      delay RA-induced differentiation and apoptosis in HL-60 cells. MZF-1 may function
      in a similar role in myelopoiesis allowing myeloid precursors to expand their
      numbers before going on to terminally differentiate.

PMID- 9593267
TI  - Unconventional rapid Erk1,2 activation is indispensable for proliferation of the
      growth factor-independent myeloid leukemic cell line KG1.
AB  - While normal hematopoietic progenitor cells are dependent on colony-stimulating
      factors for in vitro proliferation, myeloid leukemic cells are frequently factor
      independent. In this study we investigated several signalling intermediates of
      the Ras-Er1,2 pathway which may be involved in the development of growth factor
      independence. In the growth factor independent cell line KG1, an extremely short
      activation pattern of Erk1,2 with a maximum at 30 s was observed in response to
      FBS. In contrast, stimulation of the IL-3 receptor in AML193 cells resulted in a
      transient Erk activation peaking at 5 min and returning to base levels after 15
      min. Although the Erk activation in KG1 cells is short-lived, using the MEK
      inhibitor PD98059, we demonstrated that Erk phosphorylation is essential for
      proliferation of these cell lines. We also detected major differences in Shc
      phosphorylation between factor-dependent and -independent cells. These data
      suggest that Erk activation is essential for proliferation of growth factor
      dependent and -independent leukemic cells. The minimal Erk activation observed in
      KG1 cells in response to serum is sufficient for mitogenesis of these cells.

PMID- 9593268
TI  - A FISH cosmid 'cocktail' for detection of 13q deletions in chronic lymphocytic
      leukaemia--comparison with cytogenetics and Southern hybridization.
AB  - The most frequent structural chromosome abnormality in chronic lymphocytic
      leukaemia (CLL) is deletion at chromosome 13q14. Studies with Southern blot
      hybridisation have revealed deletions in the region located telomeric of the
      retinoblastoma gene in more than 40% of cases. The highest frequency of
      homozygous deletions has been found at the D13S319 locus and it is likely that a
      new tumour suppressor gene is located close to this region. We have analysed
      deletions in the D13S319 region in 20 selected CLL patients using conventional
      cytogenetic analysis, fluorescence in situ hybridisation (FISH) and Southern blot
      hybridisation. FISH and Southern hybridisation are equally efficient in detecting
      deleted clones in our study. However, FISH analysis indicate that subclones with
      different numbers of alleles in the D13S319 region can exist simultaneously. The
      cytogenetic analyses confirm that clones with different chromosomal abnormalities
      can occur in patients with CLL and that 13q14 deletions can be limited to one of
      these subclones. Furthermore, the FISH analyses show that trisomy 12 and deletion
      of 13q14 can occur in the same cell clone. Finally, our study confirms that
      mitogen stimulation of peripheral blood cells from CLL patients before FISH
      analysis may result in a sharp increase in normal appearing cells, which can hide
      leukaemic clones with deletions in the D13S319 region.

PMID- 9593269
TI  - In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM
      CSF.
AB  - We have previously demonstrated that diphtheria toxin (DT) fused to human GM-CSF
      effectively eliminates human long-term leukemia initiating cells in SCID mice.
      However, because huGM-CSF does not react with the murine GM-CSF receptor possible
      side-effects to nonleukemic tissues could not be analyzed in the AML/SCID model.
      To overcome this problem, we used murine GM-CSF fused to DT and studied the
      therapeutic index in the rat leukemia model BNML/LT12. In DT-mGM-CSF dose
      escalation experiments, severe dose-dependent toxicity to organs such as liver,
      kidney and lung was observed. Therefore, the antileukemic effects were evaluated
      with the lower doses. Daily intraperitoneal bolus injections of 75 microg/kg/day
      for 7 days induced a 3 log leukemic cell kill. The dose of 75 microg/kg/day had
      no effect on the hemopoietic progenitor cell subsets. These in vivo studies show
      that the DT-GM-CSF fusion protein can be used for specifically targeting leukemic
      cells and thus has potential as a therapeutic agent in the treatment of AML.

PMID- 9593271
TI  - Human cord blood-derived primitive progenitors are enriched in CD34+c-kit- cells:
      correlation between long-term culture-initiating cells and telomerase expression.
AB  - We studied the functional characteristics of subpopulations of cord blood-derived
      CD34+ cells expressing different levels of CD38 and c-kit antigens, using clonal
      cell culture and long-term culture with allogeneic bone marrow stromal cells or
      the MS-5 murine stromal cell line to assay long-term culture-initiating cells
      (LTC-IC) in each subpopulation. To investigate the capacity for replication,
      proliferation, and differentiation of each subpopulation of CD34+ cells, we also
      studied the correlation between LTC-IC and telomerase activity. After 5 weeks of
      coculture, LTC-IC accounted for one out of 32 CD34+CD38- cells and one out of 33
      CD34+c-kit- cells. In contrast, the frequency of LTC-IC was low in their antigen
      positive counterparts (one per 84 CD34+CD38+ cells, one per 90 CD34+c-kit(low)
      cells, and very low among CD34+c-kit(high) cells). It was noteworthy that some
      LTC-IC derived from CD34+CD38- as well as CD34+c-kit- cells generated colony
      forming cells (CFCs) after up to 9 weeks of coculture. Telomerase activity was
      consistently low in CD34+CD38- and CD34+c-kit- cells compared to CD38+ or c
      kit(high or low) cells, suggesting that CD34+CD38- or c-kit- cells are likely to
      be more quiescent. These results suggest that the CD34+CD38- and CD34+c-kit- cell
      populations are primitive stem/progenitor cells, and that the telomerase activity
      of these cells correlates with their proliferative capacity as well as their
      stage of differentiation.

PMID- 9593270
TI  - Differential growth factor requirement of primitive cord blood hematopoietic stem
      cell for self-renewal and amplification vs proliferation and differentiation.
AB  - Cord blood (CB) is an attractive alternative to bone marrow or peripheral blood
      as a source of transplantable hematopoietic tissue. However, because of the
      reduced volume, the stem cell content is limited; therefore its use as a graft
      for adult patients might require ex vivo manipulations. Two systems have been
      described that identify these stem cell populations in vitro in both mice and
      humans: (1) the long-term culture-initiating cells (LTC-IC), thus named because
      of their ability to support the growth of hematopoietic colonies (colony-forming
      cell (CFC)) for 5-6 weeks when co-cultured on stromal layers; (2) the generation
      of hematopoietic progenitors (CFC) from stroma-free liquid cultures for extended
      periods of time, which provides further indirect evidence of the presence of
      primitive stem cells. Both systems detect largely overlapping but not identical
      populations of stem cells. Thus the identification of the growth factor
      requirements for the maintenance and amplification of both systems is relevant.
      On this basis, analysis of the effects of 18 cytokine combinations on stroma-free
      liquid cultures of CB CD34+ cells, showed that: (1) after 7- and 14 day
      incubation periods, several growth factor combinations expanded the LTC-IC pool
      to a similar extent; as compared to the LTC-IC, the generation of CFC was not
      impressive; (2) time-course analysis of the LTC-IC expansion demonstrated that,
      by extending the incubation period, only a few growth factor combinations,
      containing FL, TPO, KL and IL6, could support a further, increasingly greater LTC
      IC expansion (up to 270000-fold of the initial value). In similar culture
      conditions, CFC production underwent continuous expansion, which persisted for
      over 7 months and reached values of one million-fold of the initial value. The
      simultaneous presence of FL and TPO was both necessary and sufficient to support
      this phenomenon. The addition of KL+/-IL6 did not appear to substantially modify
      the extent of LTC-IC expansion; nevertheless, it played an important role in
      sustaining an even more massive and prolonged output of CFU-GM, CFU-Mk and
      BFU/CFU-GEMM (up to 100 million-fold); (3) the presence of IL3 was found to be
      negative, in that it inhibited both the extent of LTC-IC expansion and the long
      term generation of CFC. Thus, FL and TPO appear as two unique growth factors that
      preferentially support the self-renewal of primitive stem cells; the additional
      presence of KL and IL6 seems to enhance the proliferative potential of at least
      one subpopulation of daughter stem cells, which may follow three differentiation
      pathways. Far from being definitive, our data demonstrated that massive stem cell
      expansion, in cord blood, can be obtained in reasonably well-defined culture
      conditions. This could represent an initial step towards larger scale cultures
      for transplantation and gene therapy protocols.

PMID- 9593272
TI  - Stromal factors support the expansion of the whole hemopoietic spectrum from bone
      marrow CD34+DR- cells and of some hemopoietic subsets from CD34+ and CD34+DR+
      cells.
AB  - Ex vivo expanded bone marrow CD34+DR- cells could offer a graft devoid of
      malignant cells able to promptly reconstitute hemopoiesis after transplant. We
      investigated the specific expansion requirements of this subpopulation compared
      to the more mature CD34+ and CD34+DR+ populations. The role of stromal factors
      was assessed by comparing the expansion obtained when the cells were cultured in
      (1) long-term bone marrow culture (LTBMC) medium conditioned by an irradiated
      human BM stroma (CM), (2) medium supplemented with 15% FBS (FBSM) and (3) non
      conditioned LTBMC medium (LTM) for 21 days. The effect of the addition of G-CSF
      (G) and/or of MIP-1alpha (M) to a combination of IL-3, SCF, IL-6 and IL-11 (3, S,
      6, 11) was analyzed. Compared to CD34+DR- cells, CD34+ and CD34+DR+ cells gave
      rise to a similar number of viable cells and to a lower progenitor expansion. The
      expansion potential of CD34+ and CD34+DR+ cells was equivalent in CM and in FBSM
      except for both the emergence of CD61 + megakaryocytic cells and LTC-IC
      maintenance which were improved by culture in CM. In contrast, expansion from
      CD34+DR- cells was enhanced by CM for all the parameters tested. Compared to
      FBSM, CM induced a higher level of CFU-GM and BFU-E expansion and allowed the
      emergence of CD61+ cells. HPP-CFC were maintained or expanded in CM but decreased
      in FBSM. Compared to input, the number of LTC-IC remaining after 21 days of
      CD34+DR- expansion culture was strongly decreased in FBSM and variably maintained
      or expanded in CM. Comparison with LTM indicated that stroma conditioning is
      responsible for this effect. G-CSF significantly improved CFU-GM and HPP-CFC
      expansion from CD34+DR- cells without being detrimental to the LTC-IC pool. The
      growth of CD61+ cells was significantly enhanced by G-CSF in CM. Addition of MIP
      1alpha had no significant effect either on progenitor expansion or on LTC-IC,
      regardless of culture medium. We conclude that factors present in stroma-
      conditioned medium are necessary to support the expansion of the whole spectrum
      of hematopoietic cells from CD34+DR- cells and to support the expansion of cell
      subsets from CD34+ and CD34+DR+.

PMID- 9593273
TI  - Collection of Philadelphia-negative peripheral blood progenitor cells in
      unselected patients with chronic granulocytic leukaemia. Northern Regional
      Haematology Group.
AB  - Thirty unselected patients with chronic granulocytic leukaemia (CGL), age range
      22-59 years, were treated with intensive chemotherapy and G-CSF to mobilize
      peripheral blood progenitor cells (PBPC). Chemotherapy was well tolerated and
      PBPC were collected by leukapheresis early during white cell recovery. PBPC
      collections considered adequate for engraftment were collected in 21 patients.
      Cytogenetic analysis of all collections in these patients showed >75% Ph
      negativity (range 79-100%) in 10. Successful collections, ie those >75% Ph
      negative and with total cell count of >1 x 10(6) CD34+ve cells/kg or >20 x 10(4)
      CFU-GM/kg were further analysed by Southern blot or RT-PCR. All samples were
      positive for the bcr/abl transcript. Patients with a low Sokal score (<0.8) were
      more likely to achieve a successful collection. In contrast, there was no
      association between transcript expression and likelihood of successful
      collection. We have confirmed that it is possible to mobilize and collect Ph
      negative enriched PBPC in unselected patients with CGL. This procedure is more
      likely to be successful earlier rather than later in the course of the disease.
      Whether such collections will give an advantage over unmanipulated autologous
      bone marrow transplantation in CGL requires further study, but our experience
      suggests that suitable material for autologous rescue can be obtained from
      approximately one third of eligible, unselected young patients.

PMID- 9593274
TI  - Most of CD30+ anaplastic large cell lymphoma of B cell type show a somatic
      mutation in the IgH V region genes.
AB  - Relationship and histogenesis of Hodgkin's disease (HD) and anaplastic large cell
      lymphoma (ALCL) still remain unclear. Recently, Reed-Sternberg cells or Hodgkin
      cells in HD with B cell phenotype (B-HD) are considered to originate from
      germinal center B cells, ALCLs of B cell phenotype (B-ALCL) are involved in
      diffuse large B cell lymphoma (DLBCL) as anaplastic variant, but an origin of
      tumor cells of B-ALCL has not been elucidated. We have therefore investigated
      somatic mutation of the lg heavy chain (IgH) genes among 17 cases of B-ALCL to
      clarify whether there is a difference in characteristic and origin of tumor cells
      between B-ALCL, B-HD and DLBCL. Amplificates of IgH variable (V) region of 10
      cases by the polymerase chain reaction method were sequenced and compared with
      reported germ line configurations. Nine cases (90%) with heavily somatic
      mutations were found. A case with an out-of-frame rearrangement and a case with 9
      base pairs insertion were included. The mutation pattern revealed the tumor cells
      were selected for antibody expression and discriminated from B-HD. These findings
      suggest the tumor cells of B-ALCL are derived from germinal center or
      postgerminal center (memory and effector) B cells and an origin of B-ALCL is not
      different from DLBCL.

PMID- 9593275
TI  - A new fingerprint method for sequence analysis of chromosomal translocations at
      the genomic DNA level.
AB  - Chromosomal rearrangements constitute a significant feature of leukemogenesis and
      malignant transformation in general. Nucleotide patterns in the immediate
      vicinity of the break point may provide important information about the
      underlying causalities, eg illegitimate recombination events mediated by
      topoisomerase II, Alu repeats, or VDJ recombinase. In order to facilitate the
      determination of those DNA patterns, we developed a new fingerprint approach. In
      a first step, two DNA fragments were independently amplified by long distance
      PCR: the genomic region carrying the break point and the normal nonrearranged
      counterpart. Subsequently, both PCR products were digested with restriction
      enzymes, end-labelled with a fluorescent dye, and subjected to high resolution
      polyacrylamide gel electrophoresis. By comparing the restriction patterns of the
      rearranged and the nonrearranged PCR fragments, the break points could be easily
      localized within a size range coverable by a single sequencing reaction. Finally,
      the exact DNA sequence across the break point was directly determined. The
      'fingerprint' technique is fast, reliable and enables the assay of multiple
      samples in parallel.

PMID- 9593277
TI  - Detection of Epstein-Barr virus DNA in serum of transplanted patients: a new
      diagnostic guide for lymphoproliferative diseases.

PMID- 9593276
TI  - Culture system for extensive production of CD19+IgM+ cells by human cord blood
      CD34+ progenitors.
AB  - We established a co-culture system with a monolayer of the murine bone marrow
      (BM) stroma cell line, MS-5, in which human cord blood CD34+ cells differentiated
      to CD19+ cells. The addition of stem cell factor (SCF) and granulocyte colony
      stimulating factor (G-CSF) highly enhanced the production of CD19+ cells. The
      expansion of the cell numbers was over 10(3)-fold. Furthermore, a significant
      proportion (<45%) of the cells expressed surface IgM (sIgM) after 5 weeks of co
      culture. CD34+CD19- cells also showed a similar development of CD19+ cells and
      CD19+sigM+ cells. Filter separation of MS-5 cells and CD34+ cells did not inhibit
      the growth of CD19+ cells. However, when further purified CD34+CD19-CD13- CD33-
      cells were cultured in the presence of MS-5 cells with or without a separation
      filter, CD19+ cells did not appear in the non-contact setting. This result
      suggested that the highly purified CD34+CD19-CD13-CD33- progenitors require the
      cell-cell contact for the development of CD19+ cells, whereas other CD34+
      fractions contain progenitors that do not require the contact. This co-culture
      system should be useful for the study of early human B-lymphopoiesis.

PMID- 9593278
TI  - Tetraspan transmembrane antigen levels in Burkitt lymphoma cell lines.

PMID- 9593279
TI  - Highly efficient and non-toxic DNA isolation from very old bone marrow smears.

PMID- 9593280
TI  - General Report on the European Union Concerted Action Workshop on 11q23, London,
      UK, May 1997.
AB  - Seventeen cytogenetic laboratories in eight European countries contributed
      karyotypic, hematological, clinical and follow-up data from 550 patients with an
      acquired abnormality of 11q23. The patients had acute lymphoblastic leukemia
      (254), acute myeloid leukemia (250), unspecified, undifferentiated, biphenotypic
      acute leukemia or myeloproliferative disorder (18 cases together), or
      myelodysplastic syndrome (MDS) (28). The patients were classified by cytogenetic
      subgroup as t(4;11) (183 cases), t(6;11) (30) cases), t(9;11) (125 cases),
      t(10;11) (20 cases), t(11;19) (53 cases), 'other' abnormalities of 11q23 (82
      cases) and del(11)(q23) (57 cases). Manuscripts were prepared on each cytogenetic
      subgroup, on MDS, on secondary hematological malignancies (40 cases) and on 11q23
      translocation derivatives. For each subgroup the following aspects were
      investigated: associated clinical features, additional karyotypic change,
      distribution between hematological subtypes and between different age groups,
      prognosis at different age groups, and the impact of bone marrow transplantation
      on survival. The Workshop confirmed some previous findings from smaller studies,
      challenged others, identified new chromosomal partners and threw new light on
      less well documented aspects of 11q23 malignancies. The large number of cases
      investigated in a coordinated manner gives authoritative support to the findings.
      The Workshop thus demonstrates the value of collaborative European studies in the
      cytogenetics of malignancy.

PMID- 9593281
TI  - Hematologic malignancies with t(4;11)(q21;q23)--a cytogenetic, morphologic,
      immunophenotypic and clinical study of 183 cases. European 11q23 Workshop
      participants.
AB  - A total of 183 hematologic malignancies with t(4;11)(q21;q23), including five
      variant translocations, were collected by the Workshop. Clinical, morphologic and
      immunophenotypic features were compiled, and karyotypes with variant t(4;11) or
      secondary chromosomal aberrations were reviewed. All cases were acute leukemias
      (AL): 173 acute lymphoblastic leukemias (ALL), six acute myeloid leukemias (AML),
      three unclassifiable AL, and one biphenotypic AL. Ten patients had treatment
      associated AL. Females were overrepresented (104 vs 79) and the age distribution
      was clearly nonrandom; 34% of the cases occurred in infants below the age of 12
      months. The remaining AL were evenly distributed among the other age groups, with
      the oldest patient being 79 years old. An increased white blood cell count (WBC)
      was reported in more than 90% of the cases, with hyperleukocytosis (> or =100 x
      10(9)/l) in 64%. Additional chromosomal changes were detected in 55 (30%) cases,
      most often gain of the X chromosome, i(7)(q10), and trisomy 8, with frequent
      breakpoints in 1p36, 1q21, 7q10, 11p15, 12p13, 17p11, and 17p10. All recurrent
      secondary changes resulted in genomic imbalances, in particular gains of 1q, 7q,
      8, and X and losses of 7p and 17p. Event-free and overall survival (EFS and OS)
      could be ascertained in 170 and 171 patients, respectively. Kaplan-Meier
      estimates of EFS and OS showed no differences with regard to gender, WBC, or
      presence of secondary chromosomal abnormalities, and there was no increase of EFS
      or OS among the 55 cases that had undergone bone marrow transplantation. However,
      age had an important prognostic impact, with significantly (P < 0.0001) longer
      EFS and OS in children 2-9 years old than among infants and younger children,
      patients aged between 10 and 39 years and older adults.

PMID- 9593282
TI  - The t(6;11)(q27;q23) translocation in acute leukemia: a laboratory and clinical
      study of 30 cases. EU Concerted Action 11q23 Workshop participants.
AB  - Thirty patients representing 5.5% of those collected by the 11q23 workshop had a
      t(6;11)(q27;q23). They included 27cases of acute myeloid leukemia (AML) (M1,
      three cases; M2, two cases; M4, nine cases; M4/M5, one case; M5, 12 cases) of age
      range 3-72 years and three cases of acute lymphoblastic leukemia (ALL) (B-lineage
      ALL, two cases; T-ALL, one case) of age range 0.5-13 years. In 20 cases the
      t(6;11) was the sole abnormality. In 10 cases the recurrent additional
      abnormalities were extra copies of chromosomes 8, 19, 21, or the der(6).
      Translocation t(6;11) was identified by cytogenetics alone in 13 cases. In three
      cases it was confirmed by fluorescence in situ hybridization (FISH) using whole
      chromosome paints (wcps) 6 and 11. In a further 14 cases involvement of MLL was
      demonstrated by FISH, by reverse transcriptase polymerase chain reaction (RT
      PCR), by Southern blotting (SB) or by a combination of these methods. One case
      had a direct insertion of 11 into 6-dir ins(6;11)(q27;q13q23). Molecular
      investigations showed that one case had a 3' deletion of MLL. The median overall
      survival for the patients was 12 months, indicating a poor prognosis for patients
      with a t(6;11) translocation.

PMID- 9593283
TI  - Hematological malignancies with t(9;11)(p21-22;q23)--a laboratory and clinical
      study of 125 cases. European 11q23 Workshop participants.
AB  - This paper reports clinical and cytogenetic data from 125 cases with t(9;11)(p21
      22;q32) which were accepted for a European Union Concerted Action Workshop on
      11q23. This chromosome abnormality is known to occur predominantly in acute
      myeloid leukemia (AML) FAB type M5a and less often in AML M4; in this series it
      was also found to occur, uncommonly, in other AML FAB types, in childhood acute
      lymphoblastic leukemia (ALL) (nine cases), in relatively young patients with
      myelodysplastic syndrome (MDS) (five cases), acute biphenotypic leukemia (two
      cases), and acute undifferentiated leukemia (one case). All age groups were
      represented but 50% of the patients were aged less than 15 years. The t(9;11) was
      the sole abnormality in 57 cases with AML; trisomy 8 was the most common
      additional abnormality (23 cases, including seven with further abnormalities),
      and 28 cases had other additional abnormalities. Among the t(9;11)+ve patients
      with AML, the white cell count (WBC) and age group were significant predictors of
      event-free survival; central nervous system (CNS) involvement or karyotype class
      (sole, with trisomy 8, or with other), also contributed to prognosis although our
      data could not show these to be independent factors. The best outcome was for
      patients aged 1-9 years, with low WBC, and with absence of CNS disease or
      presence of trisomy 8. For patients aged less than 15 years, the event-free
      survival for ALL patients was not significantly worse than that of AML patients.

PMID- 9593284
TI  - The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and
      clinical study of 20 patients. European 11q23 Workshop participants.
AB  - The clinical, haematological and cytogenetic data for 20 patients with an
      acquired abnormality of 11q23 and 10p have been reviewed at this workshop.
      Patients predominantly presented with de novo AML M5a and the most common
      cytogenetic finding was an inversion of part of the long arm of chromosome 11
      followed by a translocation between 11q and 10p. Band p12 represented the most
      common breakpoint on chromosome 10. The t(10;11) subgroup defined a subset of
      younger 11q23 patients, the majority of whom achieve a first complete remission
      despite the differing treatment regimens.

PMID- 9593285
TI  - The translocations, t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic
      and clinical profile of 53 patients. European 11q23 Workshop participants.
AB  - The EU Concerted Action Workshop on 11q23 Abnormalities in Hematological
      Malignancies collected 550 patients with abnormalities involving 11q23. Of these,
      53 patients had a translocation involving chromosome 11, breakpoint q23, and
      chromosome 19, breakpoint p13. Karyogram review enabled each patient to be
      further defined as t(11;19)(q23;p13.1) (21 patients) or t(11;19)(q23;p13.3) (32
      patients). There was a marked difference between the type of banding and the
      translocation identified: t(11;19)(q23;p13.1) was detected predominantly by R
      banding, whereas t(11;19)(q23;p13.3) was detected almost solely by G-banding.
      Additional change was extremely rare in patients with t(11;19)(q23;p13.1) but
      occurred in nearly half of the patients with t(11;19)(q23;p13.3). Patients with
      t(11;19)(q23;p13.1) all had leukemia of a myeloid lineage, mostly acute myeloid
      leukemia (AML), and were predominantly adult. In contrast patients with
      t(11;19)(q23;p13.3) had malignancies of both myeloid and lymphoid lineage and
      were mainly infants less than 1 year old. The survival of both groups of patients
      was generally poor, over 50% of t(11;19)(q23;p13.1) patients died within 2 years
      of diagnosis and the median survival of acute lymphoblastic leukemia (ALL)
      patients with t(11;19)(q23;p13.3) was 17.6 months.

PMID- 9593286
TI  - Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.
AB  - The MLL gene located at 11q23 has been described as a 'promiscuous' gene due its
      involvement with a large number of genetic partners. The EU Concerted Action
      Workshop on 11q23 provided 550 cases for study of which 82 showed abnormalities
      which did not involve the established translocations or deletion of 11q23. In
      these 'other' cases, which included inversions and duplications, 11q23 was found
      to be involved with 25 chromosome partners of which 10 had not been previously
      reported. These were 1q31, 4p11, 6q13, 8q21, 10q22, 10q25, 11q11, 11q21, 13q34
      and 18q23. This study demonstrated the value of the Workshop, in confirming the
      diversity of chromosomal partner sites involved with 11q23 and in the
      identification of new partners.

PMID- 9593287
TI  - Hematological malignancies with a deletion of 11q23: cytogenetic and clinical
      aspects. European 11q23 Workshop participants.
AB  - Balanced translocations of 11q23 are associated with specific clinical features
      and a poor outcome, but the relevance of deletions involving 11q23 is not clear.
      Fifty-seven patients with this deletion were collected by the Workshop, 30 had
      terminal and 27 had interstitial deletions. Twenty-seven patients had acute
      lymphoblastic leukemia (ALL), 16 had acute myeloid leukemia (AML), one had acute
      biphenotypic leukemia, one had acute undifferentiated leukemia and 12 had
      myelodysplastic syndrome (MDS). ALL patients had a median age of 7 years, median
      white blood cell count (WBC) of 15 x 10(9)/l, and 10/24 had common ALL. AML
      patients had a median age of 23 years, a median WBC of 49 x 10(9)/l, and 9/16 had
      M4 or M5. MDS patients were all adult, median age of 69 years, median WBC of 3 x
      10(9)/l, and 7/12 had refractory anemia. The clinical outcome depended on
      diagnosis: children with ALL had a better prognosis (4/16 relapsed, one died)
      than AML patients; all adults and children with AML and 5/12 MDS patients died.
      Fluorescence in situ hybridization (FISH) identified 3 del(11q23) as
      translocations or insertions. Molecular studies revealed a MLL rearrangement in
      8/10 patients. Because the involvement of MLL might be of prognostic relevance,
      identification of a del(11q23) should be an indication for FISH and molecular
      studies.

PMID- 9593288
TI  - Derivative chromosomes of 11q23-translocations in hematologic malignancies.
      European 11q23 Workshop participants.
AB  - Cytogenetic and molecular analyses of 11q23/MLL positive hematologic malignancies
      show that der(11) encodes the critical 5'MLL/3'partner gene transcript. The role
      of der(non-11) bearing the 5'partner/3'MLL fusion is less certain. The
      cytogenetic evidence for der(11) as the critical partner was investigated. Among
      1680 cases (550 workshop and 1130 published) 31 cases displayed a three-way (29
      cases) or four-way (two cases) translocation and 26 had only one of the
      derivatives. The critical junction created by t(11;n)(q23;n) was seen in all six
      cases of t(1;11)(q21;q23), in both cases of t(6;11)(q27;q23), in all six cases of
      t(11;19)(q23;p13), in nine of 11 cases with t(4;11)(q21;q23) and in 17 of 20
      cases with t(9;11)(p21-22;q23). These findings support the evidence for der(11)
      encoding the critical leukemogenic fusion transcript. In contrast, additional
      change involving duplication of one of the derivatives resulted in duplication
      only of the non-critical der(non-11) as follows: +der(4)t(4;11)(q21;q23) [9/553],
      +der(6)t(6;11)(q27;q23) [3/61], +der(9)t(9;11)(p21-22;q23) [5/291] and
      +der(19)t(11;19)(q23;p13) [6/164]. A literature search of other neoplastic
      disorders showed that either derivative may be duplicated. Duplication of the non
      critical derivative is the norm in AML patients with t(8;21)(q22;q22) or
      t(15;17)(q22;q12-21). We suggest that the genomic imbalance, rather than over
      expression of the noncritical 5'partner/3'MLL, is likely to be the important
      outcome.

PMID- 9593289
TI  - Myelodysplastic syndromes associated with 11q23 abnormalities. European 11q23
      Workshop participants.
AB  - Most hematological neoplasms associated with 11q23 chromosomal rearrangement have
      been cases of acute lymphoblastic or acute myeloid leukemia. Although cases of
      myelodysplastic syndrome (MDS) are a minority, these syndromes should also be
      recognized as part of the spectrum of hematological disorders associated with
      11q23 rearrangement. In this series of 550 patients with such rearrangement there
      were 28 (5.1%) who presented with MDS. A further five patients had a history of
      MDS but had evolved to AML by the time cytogenetic analysis was first undertaken.
      There were thus a total of 33 patients (6.0%) with an 11q23 abnormality whose
      initial presentation was as MDS. Of these 33 patients, a quarter (seven patients)
      were cases of secondary (therapy-related) MDS. Complex karyotypes and other poor
      prognosis chromosomal abnormalities such as -7 and 7q- were common and were not
      confined to secondary cases. The likelihood of presentation as MDS differed
      between different cytogenetic categories. The 28 patients in whom cytogenetic
      analysis was performed at presentation as MDS showed a wide age distribution,
      from 1 to 82 years; there were four children, two of 1 year of age. All FAB types
      of MDS were represented. Median survival was only 19.1 months. Leukemic
      transformation occurred in five patients including one case of transformation to
      a biphenotypic M5a/T-lineage acute leukemia.

PMID- 9593290
TI  - Secondary acute leukemia and myelodysplastic syndrome with 11q23 abnormalities.
      EU Concerted Action 11q23 Workshop.
AB  - Forty of the 550 patients (7%) entered to the 11q23 Workshop had secondary (s)
      acute lymphoblastic leukemia (nine cases), s-acute myeloid leukemia (25 cases,
      predominantly of FAB type M5), s-acute leukemia unspecified (one case) or s
      myelodysplastic syndrome (five cases) following treatment for a primary
      malignancy. Breast cancer (12 cases) and non-Hodgkin's lymphoma (eight cases)
      were the most frequent primaries. Twenty-three patients had been treated with
      either an epipodophyllotoxin (seven patients) or an anthracycline (10 cases) or
      both (four cases) frequently combined with alkylating agents (12 cases) and with
      radiotherapy (six cases). Two further patients had alkylating agents and two had
      radiotherapy alone. Time between diagnosis of the primary and secondary
      malignancy was between 10 months and 22 years (median 24 months). The incidence
      of secondary malignancies in 11q23 subgroups was: t(11;19)(q23;p13.1) (33%),
      t(9;11) (8%), t(4;11) (5.5%), t(10;11)(5%), t (6;11) (3%), del11q23(2%) and 10
      patients had a rare 'other' abnormality. No associations were seen between type
      of prior malignancy and 11q23 subgroup, or between prior malignancy and leukemia
      subtype. Remission, when achieved (32 patients), was short (median 5 months). Two
      patients survived following a bone marrow transplant for s-leukemia and s
      myelodysplastic syndrome.

PMID- 9593291
TI  - The complete sequence of the locus of enterocyte effacement (LEE) from
      enteropathogenic Escherichia coli E2348/69.

PMID- 9593292
TI  - The Escherichia coli ATP-binding cassette (ABC) proteins.
AB  - The recent completion of the Escherichia coli genome sequence (Blattner et al.,
      1997) has permitted an analysis of the complement of genomically encoded ATP
      binding cassette (ABC) proteins. A total of 79 ABC proteins makes this the
      largest paralogous family of proteins in E. coli. These 79 proteins include 97
      ABC domains (as some proteins include more than one ABC domain) and are
      components of 69 independent functional systems (as many systems involve more
      than one ABC domain). The ABC domains are often, but not exclusively, the energy
      generating domains of multicomponent membrane-bound transporters. Thus, 57 of the
      69 systems are ABC transporters, of which 44 are periplasmic-binding protein
      dependent uptake systems and 13 are presumed exporters. The genes encoding these
      ABC transporters occupy almost 5% of the genome. Of the 12 systems that are not
      obviously transport related, the function of only one, the excision repair
      protein UvrA, is known. A phylogenetic analysis suggests that the majority of ABC
      proteins can be assigned to 10 subfamilies. Together with statistical and,
      importantly, biological evidence, this analysis provides insight into the
      evolution and function of the ABC proteins.

PMID- 9593293
TI  - Cytochrome c biogenesis is involved in the transposon Tn5-mediated bleomycin
      resistance and the associated fitness effect in Escherichia coli.
AB  - The transposon Tn5 ble gene and the Escherichia coli alkylation-inducible aidC
      locus are co-operatively involved in the resistance to the anti-cancer drug and
      DNA-cleaving agent bleomycin and enhance fitness of bacteria in the absence of
      the drug. In this report, we demonstrate that the aidC locus is identical to
      nrfG, the last gene of the nrf operon involved in the periplasmic formate
      dependent nitrite reduction. In the presence of Ble, NrfG expression is
      specifically induced and restores both bleomycin resistance and its associated
      beneficial growth effect in an aidC- strain. In vitro DNA protection assays
      reveal that purified Ble prevents bleomycin-mediated DNA breakage, as do
      bleomycin-binding proteins. Similarities between haems of the cytochrome c
      biogenesis nrf pathway and iron bleomycin suggest a DNA repair-independent
      molecular mechanism for both bleomycin resistance and increased viability. The
      Ble protein binds bleomycin and prevents DNA breakage. It also induces the nrf
      locus that may assimilate bleomycin into haem for extracellular transport or
      inactivate bleomycin. Inactivation of potent DNA oxidants confers a better
      fitness to the bacterium carrying the transposon, suggesting a symbiotic
      relationship between host and transposon.

PMID- 9593294
TI  - ClpX and ClpP are essential for the efficient acquisition of genes specifying
      type IA and IB restriction systems.
AB  - Efficient acquisition of genes that encode a restriction and modification (R-M)
      system with specificities different from any already present in the recipient
      bacterium requires the sequential production of the new modification enzyme
      followed by the restriction activity in order that the chromosome of the
      recipient bacterium is protected against attack by the restriction endonuclease.
      We show that ClpX and ClpP, the components of ClpXP protease, are necessary for
      the efficient transmission of the genes encoding EcoKI and EcoAI, representatives
      of two families of type I R-M systems, thus implicating ClpXP in the modulation
      of restriction activity. Loss of ClpX imposed a bigger barrier than loss of ClpP,
      consistent with a dual role for ClpX, possibly as a chaperone and as a component
      of the ClpXP protease. Transmission of genes specifying EcoKI was more dependent
      on ClpX and ClpP than transmission of the genes for EcoAI. Sensitivity to absence
      of the protease was also influenced by the mode of gene transfer; conjugative
      transfer and transformation were more dependent on ClpXP than transduction. In
      the absence of either ClpX or ClpP transfer of the EcoKI genes by P1-mediated
      transduction was impaired, transfer of the EcoAI genes was not.

PMID- 9593295
TI  - Analyses of the cag pathogenicity island of Helicobacter pylori.
AB  - Most strains of Helicobacter pylori from patients with peptic ulcer disease or
      intestinal-type gastric cancer carry cagA, a gene that encodes an immunodominant
      protein of unknown function, whereas many of the strains from asymptomatically
      infected persons lack this gene. Recent studies showed that the cagA gene lies
      near the right end of a approximately 37kb DNA segment (a pathogenicity island,
      or PAI) that is unique to cagA+ strains and that the cag PAI was split in half by
      a transposable element insertion in the reference strain NCTC11638. In
      complementary experiments reported here, we also found the same cag PAI, and
      sequenced a 39 kb cosmid clone containing the left 'cagII' half of this PAI.
      Encoded in cagII were four proteins each with homology to four components of
      multiprotein complexes of Bordetella pertussis ('Ptl'), Agrobacterium tumefaciens
      ('Vir'), and conjugative plasmids ('Tra') that help deliver pertussis toxin and T
      (tumour inducing) and plasmid DNA, respectively, to target eukaryotic or
      prokaryotic cells, and also homologues of eukaryotic proteins that are involved
      in cytoskeletal structure. To the left of cagII in this cosmid were genes for
      homologues of HsIU (heat-shock protein) and Era (essential GTPase); to the right
      of cagII were homologues of genes for a type I restriction endonuclease and ion
      transport functions. Deletion of the cag PAI had no effect on synthesis of the
      vacuolating cytotoxin, but this deletion and several cag insertion mutations
      blocked induction of synthesis of proinflammatory cytokine IL-8 in gastric
      epithelial cells. Comparisons among H. pylori strains indicated that cag PAI gene
      content and arrangement are rather well conserved. We also identified two genome
      rearrangements with end-points in the cag PAI. One, in reference strain
      NCTC11638, involved IS605, a recently described transposable element (as also
      found by others). Another rearrangement, in 3 of 10 strains tested (including
      type strain NCTC11637), separated the normally adjacent cagA and picA genes and
      did not involve IS605. Our results are discussed in terms of how cag-encoded
      proteins might help trigger the damaging inflammatory responses in the gastric
      epithelium and possible contributions of DNA rearrangements to genome evolution.

PMID- 9593296
TI  - In vivo studies on the positive control function of NifA: a conserved hydrophobic
      amino acid patch at the central domain involved in transcriptional activation.
AB  - The eubacterial enhancer-binding proteins activate transcription by binding to
      distant sites and, simultaneously, contacting the RNA polymerase r54 promoter
      complex (Esigma54). The positive control function is located at the central
      domain of these proteins, but it is not know which specific region has the
      determinants for the interaction with Esigma54. Here, we present genetic evidence
      that a small region of hydrophobic amino acids, previously denominated C3, at the
      central domain of Bradyrhizobium japonicum NifA is involved in positive control.
      We obtained 26 missense mutants along this conserved region. Among these, only
      strains expressing the NifA(F307-->Y) and NifA(A310-->S) mutant proteins retained
      some of the transcriptional activity (<20%), whereas those carrying NifA(E298-
      >D) and NifA(T308-->S) had very low but detectable activity (< 1.0%). The rest of
      the NifA mutants did not induce any measurable transcriptional activity. When
      expressed in the presence of wild-type NifA, the great majority of the mutants
      displayed a dominant phenotype, suggesting that their oligomerization
      determinants were not altered. In vivo dimethyl-sulphate footprinting experiments
      for a subset of the NifA mutants showed that they were still able to bind
      specifically to DNA. Analysis of intragenic supressors highlight the functional
      role of a hydroxyl group at position 308 to activate transcription.

PMID- 9593297
TI  - A role for the Pcl9-Pho85 cyclin-cdk complex at the M/G1 boundary in
      Saccharomyces cerevisiae.
AB  - PHO85 is a cyclin-dependent kinase (CDK) with roles in phosphate and glycogen
      metabolism and cell cycle progression. As a CDK, Pho85 is activated by
      association with Pho85 cyclins (Pcls), of which 10 are known. PCL1, PCL2 and PCL9
      are the only members of the Pho85 cyclin family that are expressed in a cell
      cycle-regulated pattern. We found that PCL9 is expressed in late M/early G1 phase
      of the cell cycle and is activated by the transcription factor, Swi5. This
      pattern of regulation is different from PCL1 and PCL2, which are expressed later
      in G1 phase and are regulated primarily by the transcription factor SBF. Co
      immunoprecipitation experiments using in vitro translated proteins showed that
      Pcl9 and Pho85 form a complex. Furthermore, immunoprecipitated Pcl9 complexes
      from yeast lysates were capable of phosphorylating the exogenous substrate Pho4.
      The Pcl9-associated kinase activity was dependent on PHO85, showing that Pcl9 and
      Pho85 form a functionally active kinase complex in vivo. Deletion of PCL9 in
      diploid cells caused random, rather than bipolar, budding in 18% of cells. In
      contrast, deletion of PCL2, the closest relative of PCL9, had no effect on the
      budding pattern. Deleting more members of the PCL1,2 subfamily (which includes
      PCL9) increased the percentage of random budding in the cell population. When all
      members of the PCL1,2 subfamily were deleted, 73% of cells budded randomly, a
      value similar to that obtained when the CDK partner PHO85 was deleted. Our
      results show that PCL9 and PHO85 form a functional kinase complex and suggest a
      role for Pho85 CDKs at the M/G1 boundary.

PMID- 9593298
TI  - Internalin B is essential for adhesion and mediates the invasion of Listeria
      monocytogenes into human endothelial cells.
AB  - Listeria monocytogenes causes rhombencephalitis in humans and animals and also
      affects the fetus in utero, causing disseminated sepsis. In both instances, the
      infection occurs by the crossing of endothelial cells lining a physiological
      barrier, the blood-brain barrier or the transplacental barrier. In this study,
      the ability of L. monocytogenes wild-type EGD to invade human umbilical vein
      endothelial cells (HUVECs) was evaluated using wild-type bacteria and isogenic
      Listeria mutants. Here, we show that invasion of HUVECs by L. monocytogenes is
      dependent on the expression of the internalin B gene product. This was
      demonstrated in several ways. First, L. monocytogenes strains lacking the inlB
      gene did not invade HUVECs. Secondly, avid invasion was obtained when a strain
      deleted for inlAB was complemented with a plasmid harbouring inlB only, whereas
      strains expressing inlA did not enter HUVECs. Thirdly, entry of wild-type EGD
      could be blocked effectively with antibodies to InlB. Fourthly, cell binding
      assays and flow cytometry with HUVECs showed binding of purified InlB, but not
      InlA, suggesting a tropism of InlB for this cell type. Finally, physical
      association of purified native InlB with the surface of non-invasive mutants
      dramatically increased their ability to invade HUVECs. In laser-scanning confocal
      microscopy, binding of InlB was observed as focal and localized patches on the
      cell surface of HUVECs. Qualitative examination of the entry process by scanning
      electron microscopy revealed that both wild-type EGD and a recombinant strain
      overexpressing only InlB enter HUVECs in a similar fashion. The entry process was
      polarized, involved single bacteria and occurred over the entire surface of
      endothelial cells.

PMID- 9593299
TI  - Alteration in the contents of unsaturated fatty acids in dnaA mutants of
      Escherichia coli.
AB  - DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli,
      has a high affinity for acidic phospholipids containing unsaturated fatty acids.
      We have examined here the fatty acid composition of phospholipids in dnaA
      mutants. A temperature-sensitive dnaA46 mutant showed a lower level of
      unsaturation of fatty acids (ratio of unsaturated to saturated fatty acids) at 42
      degrees C (non-permissive temperature) and at 37 degrees C (semi-permissive
      temperature), but not at 28 degrees C (permissive temperature), compared with the
      wild-type strain. Plasmid complementation analysis revealed that the dnaA46
      mutation is responsible for the phenotype. Other temperature-sensitive dnaA
      mutants showed similar results. On the other hand, a cold-sensitive dnaAcos
      mutant, in which over-initiation of DNA replication occurs at low temperature (28
      degrees C), showed a higher level of unsaturation of fatty acids at 28 degrees C.
      Based on these observations, we discuss the role of phospholipids in the
      regulation of the activity of DnaA protein.

PMID- 9593300
TI  - Circularization of Tn916 is required for expression of the transposon-encoded
      transfer functions: characterization of long tetracycline-inducible transcripts
      reading through the attachment site.
AB  - A detailed transcriptional analysis of the conjugative transposon Tn916 was
      carried out, which revealed that transcription of the transfer functions requires
      excision of the element and dramatically increases in the presence of
      tetracycline. The key components of this regulatory system are two contiguous
      transposon-borne genes, orf7 and orf8, located downstream from and having the
      same polarity of transcription as the tetracycline resistance determinant tetM.
      The gene orf7 encodes a 140-amino-acid (aa) protein exhibiting limited homology
      with sigmaF of Bacillus subtilis, whereas orf8 encodes a 76-aa peptide that does
      not share any sequence homology with any cognate proteins. In the presence of
      tetracycline, an attenuation mechanism enables the transcription of orf7 and orf8
      from the tetM promoter. The resulting increased synthesis of ORF7 and ORF8
      activates the promoter Porf7 located upstream from orf7, which then directs the
      expression of the transfer functions in the transposon circular intermediate
      through long transcripts encompassing the attachment site. The apparently non
      regulated promoter Pxis located upstream of the excisionase encoding gene xis
      could also participate in the expression of the tra genes. We also demonstrate
      that Tn916 carries another regulated promoter, Porf9, which directs transcription
      of a single gene, orf9, located downstream from and transcribed counterclockwise
      to tetM. This gene encodes a 117-aa putative transcriptional repressor, but the
      exact role of this protein in the mobility of Tn916, as well as the regulation of
      its expression, remains to be elucidated. Our results constitute the molecular
      basis for the observation that tetracycline increased the transfer frequency of
      this type of element.

PMID- 9593301
TI  - Sites internal to the coding regions of phoA and pstS bind PhoP and are required
      for full promoter activity.
AB  - Bacillus subtilis PhoP and PhoR, a pair of two-component regulatory proteins,
      regulate the phosphate starvation response. Here, we used two other pho regulon
      promoters, the phoA and pstS promoters, to examine the mechanism of PhoP-specific
      activation of its target promoters. Both gel shift and DNase I footprinting
      assays indicate that PhoP bound to the two promoters. Unphosphorylated PhoP bound
      only to the multiple TTAACA-like sequences upstream of these two promoters, while
      phosphorylated PhoP extended the binding region in both the 5' and the 3'
      direction and, additionally, protected sequences internal to the coding region of
      these two genes. The PhoP binding sites in the coding region were necessary for
      full induction from either promoter during phosphate starvation. Deletion of
      these sites eliminated approximately 75% and 45% of the induced promoter activity
      of the phoA and pstS promoters respectively. In vitro transcription assays using
      the phoA promoters with various 3' ends confirmed the requirement of the PhoP-P
      binding to the coding region for full promoter activity. The multiple TTAACA-like
      sequences in the phoA and pstS promoters were essential for promoter activity,
      and deletion of one or more of these sequences in either promoter eliminated the
      promoter activity. Two pairs of TTAACA-like sequences were required for efficient
      PhoP binding and were suggested to be one B. subtilis Pho box. Based on our data,
      we have proposed a model for activation of the phoA and the pstS promoter by
      PhoP.

PMID- 9593302
TI  - Aromatic ligand binding and intramolecular signalling of the phenol-responsive
      sigma54-dependent regulator DmpR.
AB  - The Pseudomonas-derived sigma54-dependent regulator DmpR has an amino-terminal A
      domain controlling the specificity of activation by aromatic effectors, a central
      C-domain mediating an ATPase activity essential for transcriptional activation
      and a carboxy-terminal D-domain involved in DNA binding. In the presence of
      aromatic effectors, the DmpR protein promotes transcription from the -24, -12 Po
      promoter controlling the expression of specialized (methyl)phenol catabolic
      enzymes. Previous analysis of DmpR has led to a model in which the A-domain acts
      as an interdomain repressor of DmpR's ATPase and transcriptional promoting
      property until specific aromatic effectors are bound. Here, the autonomous nature
      of the A-domain in exerting its biological functions has been dissected by
      expressing portions of DmpR as independent polypeptides. The A-domain of DmpR is
      shown to be both necessary and sufficient to bind phenol. Analysis of phenol
      binding suggests one binding site per monomer of DmpR, with a dissociation
      constant of 16 microM. The A-domain is also shown to have specific affinity for
      the C-domain and to repress the C-domain mediated ATPase activity in vitro
      autonomously. However, physical uncoupling of the A-domain from the remainder of
      the regulator results in a system that does not respond to aromatics by its
      normal derepression mechanism. The mechanistic implications of aromatic non
      responsiveness of autonomously expressed A-domain, despite its demonstrated
      ability to bind phenol, are discussed.

PMID- 9593304
TI  - High-frequency intracellular infection and erythrogenic toxin A expression
      undergo phase variation in M1 group A streptococci.
AB  - A clonal variant of serotype M1 group A streptococcus, strain 90-131,
      disseminated to several continents, where it was associated with severe systemic
      infections and toxic shock. Although this strain harbours the speA gene and is
      efficiently internalized by human epithelial cells, clinical isolates often fail
      to express the erythrogenic toxin under laboratory growth conditions. Cultures of
      strain 90-131 were observed to phase vary between small, dry, compact and larger,
      more mucoid colonies. The former were shown to be poorly internalized by
      epithelial cells. Analysis of RNA by Northern hybridization demonstrated that the
      emml, hasA and speA genes were weakly transcribed in cultures derived from the
      small colonies and highly transcribed in those derived from the large colonies.
      An insertion mutation in mga (the multigene activator) downregulated the invasion
      of epithelial cells and the transcription of emm1 and hasA, but had little impact
      on the transcription of speA. These are the first data to suggest the existence
      of a common regulatory circuit linking intracellular invasion, M protein,
      hyaluronic acid capsule and erythrogenic toxin expression by group A
      streptococcus. Moreover, the genetic instability of toxin expression exhibited by
      this serotype may impact on laboratory studies that attempt to associate toxin
      production with toxic shock.

PMID- 9593305
TI  - Combinational variation of restriction modification specificities in Lactococcus
      lactis.
AB  - Three genes coding for a type I R-M system related to the class C enzymes have
      been identified on the chromosome of Lactococcus lactis strain IL1403. In
      addition, plasmids were found that encode only the HsdS subunit that directs R-M
      specificity. The presence of these plasmids in IL1403 conferred a new R-M
      phenotype on the host, indicating that the plasmid-encoded HsdS is able to
      interact with the chromosomally encoded HsdR and HsdM subunits. Such
      combinational variation of type I R-M systems may facilitate the evolution of
      their specificity and thus reinforce bacterial resistance against invasive
      foreign unmethylated DNA.

PMID- 9593303
TI  - Protein translocation into host epithelial cells by infecting enteropathogenic
      Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) causes diarrhoea in young children. EPEC
      induces the formation of actin pedestal in infected epithelial cells. A type III
      protein secretion system and several proteins that are secreted by this system,
      including EspB, are involved in inducing the formation of the actin pedestals. We
      have demonstrated that contact of EPEC with HeLa cells is associated with the
      induction of production and secretion of EspB. Shortly after infection, EPEC
      initiates translocation of EspB, and EspB fused to the CyaA reporter protein
      (EspB-CyaA), into the host cell. The translocated EspB was distributed between
      the membrane and the cytoplasm of the host cell. Translocation was strongly
      promoted by attachment of EPEC to the host cell, and both attachment factors of
      EPEC, intimin and the bundle-forming pili, were needed for full translocation
      efficiency. Translocation and secretion of EspB and EspB-CyaA were abolished in
      mutants deficient in components of the type III protein secretion system,
      including sepA and sepB mutants. EspB-CyaA was secreted but not translocated by
      an espB mutant. These results indicate that EspB is both translocated and
      required for protein translocation by EPEC.

PMID- 9593306
TI  - The redox- and fixed nitrogen-responsive regulatory protein NIFL from Azotobacter
      vinelandii comprises discrete flavin and nucleotide-binding domains.
AB  - Azotobacter vinelandii NIFL is a nitrogen fixation-specific regulatory
      flavoprotein that modulates the activity of the transcriptional activator NIFA in
      response to oxygen and fixed nitrogen in vivo. NIFL is also responsive to ADP in
      vitro. Limited proteolysis of NIFL indicates that it comprises a relatively
      stable N-terminal domain and a C-terminal domain that is protected from trypsin
      digestion in the presence of adenosine nucleotides. ATP protects the protein from
      cleavage in the vicinity of potential nucleotide-binding sites in the C-terminus,
      whereas ADP protects the entire C-terminal domain. NIFL has an apparent Kd of 130
      microM for ATP and 16 microM for ADP. The purified N-terminal domain has an
      identical UV/visible absorption spectrum to the wild-type protein and is reduced
      by sodium dithionite, demonstrating that it is a flavin-binding domain. The
      isolated N-terminal domain does not inhibit NIFA activity. A subdomain fragment
      containing 160 residues of the C-terminal region, including the nucleotide
      binding sites, is also not competent to inhibit NIFA. Removal of the first 146
      residues of NIFL, which includes a conserved S-motif (PAS-like domain), found in
      a large family of sensory proteins from eubacteria, archea and eukarya eliminates
      the redox response. However, this truncated protein remains competent to inhibit
      NIFA activity in response to ADP in vitro and to the level of fixed nitrogen in
      vivo. The redox and nitrogen-sensing functions of A. vinelandii NIFL are
      therefore separable and are discrete functions of the protein.

PMID- 9593307
TI  - In vitro biosynthesis of the Pseudomonas aeruginosa quorum-sensing signal
      molecule N-butanoyl-L-homoserine lactone.
AB  - In Pseudomonas aeruginosa, synthesis of the quorum-sensing signal molecules N
      butanoyl-L-homoserine lactone (BHL) and N-hexanoyl-L-homoserine lactone (HHL)
      requires the Luxl homologue Rhll(Vsml). By using thin-layer chromatography in
      conjunction with high-performance liquid chromatography (HPLC) and mass
      spectrometry, we show that purified Rhll can catalyse the biosynthesis of BHL and
      HHL using either S-adenosylmethionine (SAM) or homoserine lactone (HSL) but not
      homoserine as the source of the homoserine lactone moiety. As we were unable to
      detect homoserine lactone in cytoplasmic extracts of Escherichia coli, we
      conclude that SAM is the natural substrate for Rhll-directed N-acylhomoserine
      lactone (AHL) biosynthesis. The N-acyl chain of BHL and HHL can be supplied by
      the appropriately charged coenzyme A derivative (either n-butanoyl-CoA or n
      hexanoyl-CoA). The specificity of Rhll for charged CoA derivatives is
      demonstrated as Rhll was unable to generate AHLs detectable in our bioassays from
      acetyl-CoA, malonyl-CoA, n-octanoyl-CoA, n-decanoyl-CoA, DL-beta-hydroxybutanoyl
      CoA or crotonoyl-CoA. Rhll was also unable to use N-acetyl-S-3
      oxobutanoylcysteamine, a chemical mimic for 3-oxobutanoyl-CoA. Furthermore, the
      Rhll-catalysed synthesis of BHL and HHL was most efficiently driven when NADPH
      was included in the reaction mixture.

PMID- 9593308
TI  - Involvement of products of the nrfEFG genes in the covalent attachment of haem c
      to a novel cysteine-lysine motif in the cytochrome c552 nitrite reductase from
      Escherichia coli.
AB  - Cytochrome c552 is the terminal component of the formate-dependent nitrite
      reduction pathway of Escherichia coli. In addition to four 'typical' haem-binding
      motifs, CXXCH-, characteristic of c-type cytochromes, the N-terminal region of
      NrfA includes a motif, CWSCK. Peptides generated by digesting the cytochrome from
      wild-type bacteria with cyanogen bromide followed by trypsin were analysed by on
      line HPLC MS/MS in parent scanning mode. A strong signal at mass 619,
      corresponding to haem, was generated by fragmentation of a peptide of mass 1312
      that included the sequence CWSCK. Neither this signal nor the haem-containing
      peptide of mass 1312 was detected in parallel experiments with cytochrome that
      had been purified from a transformant unable to synthesize NrfE, NrfF and NrfG:
      this is consistent with our previous report that NrfE and NrfG (but not NrfF) are
      essential for formate-dependent nitrite reduction. Redox titrations clearly
      revealed the presence of high and low mid-point potential redox centres. The best
      fit to the experimental data is for three n=1 components with mid-point redox
      potentials (pH 7.0) of +45 mV (21% of the total absorbance change), -90 mV (36%
      of the total) and -210mV (43% of the total). Plasmids in which the lysine codon
      of the cysteine-lysine motif, AAA, was changed to the histidine codon CAT (to
      create a fifth 'typical' haem c-binding motif), or to the isoleucine and leucine
      codons, ATT and CTT, were unable to transform a Nrf deletion mutant to Nrf+ or to
      restore formate-dependent nitrite reduction to the transformants. The presence of
      a 50 kDa periplasmic c-type cytochrome was confirmed by staining proteins
      separated by SDS-PAGE for covalently bound haem, but the methyl-viologen
      dependent nitrite reductase activities associated with the mutated proteins,
      although still detectable, were far lower than that of the native protein. The
      combined data establish not only that there is a haem group bound covalently to
      the cysteine-lysine motif of cytochrome c552 but also that one or more products
      of the last three genes of the nrf operon are essential for the haem ligation to
      this motif.

PMID- 9593310
TI  - Basal and induced nitric oxide and cGMP productions are decreased in senescent
      cultured rat articular chondrocytes.
AB  - The effects of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and
      lipopolysaccharide (LPS) on the productions of nitric oxide (NO) and cGMP by
      cultured articular chondrocyte (AC) monolayers from 1-, 8- and 18-month old male
      Wistar rats were studied. It was found that basal NO and cGMP productions
      decrease with the age of animals. The productions were more than 2-fold greater
      in cells from 1-month old rats then in cells from older animals. IL-1, TNF-alpha,
      and LPS stimulated all three types of cells to produce NO and cGMP in a time- and
      concentration-dependent manner. Although the cells from young animals produced
      more NO per microg DNA, the older counterparts were more sensitive to these
      agents since they produced more NO upon stimulation then the corresponding non
      stimulated controls. At the concentration of 10(-3) M, the nitric oxide synthase
      (NOS) inhibitor, Ng-monomethyl-L-arginine (L-NMA), blocked, although
      incompletely, both the basal and stimulated NO and cGMP productions in cells from
      the 1 and 8-month old rats and only induced productions in 18-month old
      counterparts. These results show a decreased capacity of unstimulated- and
      stimulated-AC from old rats to produce NO and cGMP in culture, which may affect
      the ageing cells in some yet unknown way.

PMID- 9593309
TI  - Pharmacological intervention in age-associated brain disorders by Flupirtine:
      Alzheimer's and prion diseases.
AB  - Alzheimer's disease, a major form of dementia in the elderly has become an
      increasingly important health problem in developed countries. In vitro studies on
      primary neurons demonstrate that Flupirtine (Katadolon) at a concentration of 1
      microg/ml, significantly reduces the neurotoxic (apoptotic) effect displayed by A
      beta25-35, a segment of the amyloid beta-protein precursor the etiologic agent of
      Alzheimer's disease. Flupirtine, which has been in clinical use since 10 years
      ago, prevents the toxic effect of PrP, the presumed etiologic agent of the
      Creutzfeldt-Jakob disease as well as the excitatory amino acid glutamate on
      cortical neurons. Flupirtine displays a bimodal activity. Its strongest
      cytoprotective effect against glutamate-induced neurotoxicity was measured if
      administered at least 120 min prior to the addition of the glutamate. A likewise
      potent anti-apoptotic activity was measured if cells were simultaneously
      incubated with Flupirtine and the apoptotic inducers. Administration of
      Flupirtine during postincubation time in the experiments with glutamate did not
      result in neuroprotection. In parallel with the determination of the effect of
      Flupirtine on the toxin (A beta, PrP or glutamate)-induced neuronal death the
      effect of the drug on the intracellular Ca2+ level [Ca2+]i, was measured. It is
      well established that incubation of neurons with glutamate causes an increase in
      [Ca2+]i. It was found that a simultaneous administration of Flupirtine and
      glutamate did not reduce the glutamate-induced high Ca2+ level. Only if the cells
      had been preincubated for approximately 30 min with the drug the intracellular
      Ca2+ level was significantly lower. Experimental evidence given here shows that
      the molecular basis for the antiapoptotic effect of Flupirtine against glutamate,
      triggered during pre-incubation, is an increased expression of the protooncogene
      bcl-2. The neuroprotective effect determined during coincubation with the inducer
      is attributed to a normalization of the glutathione level which dropped in the
      presence of the inducers. It is concluded that Flupirtine is a promising drug to
      treat neurodegenerative disorders occurring with age, e.g. Alzheimer's disease
      and prion based diseases, like Creutzfeldt-Jakob disease. This conclusion is
      corroborated by the favourable pharmacokinetic profile of Flupirtine.

PMID- 9593311
TI  - Decreased mRNA levels for exocytotic proteins in the pituitary of aged rats.
AB  - Several protein components that are involved in the molecular regulation of
      transmitter release have been identified in neuronal, neuroendocrine and
      endocrine tissues. The expression of VAMP-2 (vesicle-associated membrane
      protein), munc-18 (mammalian homologue of unc-18) and SNAP-25 (synaptosomal
      associated protein of 25 kDa) mRNA was studied in the rat anterior and
      intermediate pituitary gland of adult (2 months) and old (24 months) rats using
      in situ hybridization. In the pituitary anterior lobe of aged rats, there was a
      significant decrease in VAMP-2 (33%), munc-18 (17%) and SNAP-25 (20%) mRNA as
      compared to adult rats. In the intermediate lobe, there was a significant
      decrease in VAMP-2 (48%) and SNAP-25 (32%) mRNA of aged rats, whereas munc-18
      mRNA levels were not significantly changed. Pituitaries from aged rats showed an
      increase in size which was paralleled by a significant decrease in the number of
      cells per unit area in the intermediate lobe, whereas the number was unaltered in
      the anterior lobe. The results suggest a genuine decrease in mRNA for exocytotic
      protein mRNA in the anterior pituitary, but that part of the decrease in the
      expression of VAMP-2 and SNAP-25 mRNA in the intermediate lobe can be explained
      by a decreased number of cells per unit area. The decline in anterior pituitary
      hormone secretion reported in aged rats appears to be parallelled by a down
      regulation in mRNA levels for several proteins involved in the molecular
      regulation of exocytosis.

PMID- 9593312
TI  - Hutchinson-Gilford progeria: faithful DNA maintenance, inheritance and allelic
      transcription of beta(1-4) galactosyltransferase.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a fatal segmental aging disorder
      affecting children. There is a paucity of prior data at the nucleotide level on
      DNA maintenance in HGPS. We have examined the specific nucleotide sequences and
      production of allelic transcripts from the locus GGTB2 encoding beta(1-4)
      galactosyltransferase. Quantitative Northern blots of mRNA from HGPS and control
      fibroblasts indicated identical mature beta(1-4) galactosyltransferase transcript
      sizes and amounts, regardless of their altered glycosylation status. DNA
      sequencing of cDNA derived from HGPS beta(1-4) galactosyltransferase mRNA
      populations confirmed the encoded amino acid sequence was unaffected. Population
      studies of 41 unrelated individuals provided allelic frequency estimates for a
      novel FokI polymorphism, which was identified in two of six progeria cell
      strains. The polymorphism was faithfully inherited in a progeria pedigree in a
      Mendelian manner. Furthermore, the polymorphism provided direct evidence through
      sequencing of reverse transcription polymerase chain reaction products that both
      alleles were transcribed and generated mature mRNA. Any defects in transcripts
      were below detectable levels over the lengths of coding sequences examined,
      despite multiple replication events from conception leading to the production and
      maintenance of patient-derived cells. These results indicate faithful
      transcription in HGPS.

PMID- 9593313
TI  - Age-dependent expression of fibrosis-related genes and collagen deposition in the
      rat myocardium.
AB  - OBJECTIVES: We sought to characterize the evolution, during maturational growth
      and early ageing, of the messenger abundance of four genes involved in cardiac
      fibrosis regulation (procollagens alpha2(I) and alpha1(III), transforming growth
      factors beta1, and beta3) and corroborate it with the alterations in collagen
      deposition in cardiac interstitium and around coronary arteries. METHODS:
      Messenger RNA was quantified in LV and RV of 2-, 6-, 12- and 19-month-old male
      Sprague-Dawley rats (n = 5 per group) with Northern blot analysis. Collagen
      deposition was quantified with a semi-automated image analyser on Sirius red
      stained sections of LV tissue. RESULTS: There was an age-related monotonous
      decrease of procollagen type I (COL-I) transcript abundance in LV (p < 0.001) but
      not in RV. Procollagen type III (COL-III) expression decreased rapidly during
      maturational growth, both in LV and RV. On the other hand, collagen deposition in
      myocardial interstitium and around coronary arteries was slightly augmented
      during the maturational period of life (2-12 months), but with a higher rate
      during early ageing (up to 19 months). This was not accompanied by a significant
      thickening of the wall of coronary arteries. Transforming growth factor beta1,
      (TGF-beta1) and transforming growth factor beta3 (TGF-beta3) transcript abundance
      showed no major variations during ageing. CONCLUSIONS: These results reflect a
      striking ventricular difference regarding the age-dependent expression of COL-I.
      The expression of TGF-beta(s), pleiotropic factors known to influence collagen
      pathway at different levels, does not seem to be profoundly altered during
      ageing. The discrepancy between protein and COL-I and COL-III mRNA levels
      indicates differences in age-related mRNA stability and/or regulation of collagen
      translation.

PMID- 9593314
TI  - Differential display analysis of gene expression indicates that age-related
      changes are restricted to a small cohort of genes.
AB  - It is clear that there is a genetic component associated with the ageing process.
      Although evolutionary theory has suggested that the activity of certain genes may
      facilitate ageing by favouring resource utilisation by the germ cells at the
      expense of somatic cells, there is reason to believe that the senescent
      phenotype, which is the endpoint of the ageing process, may be due to alterations
      in the levels of expression of other genes. To investigate this situation we have
      used the differential display technique to survey gene expression during ageing
      of the rat brain, heart and liver. By optimising this technique it is possible to
      identify up to 10000-14000 PCR products, which represent genes expressed in the
      tissue under study. Interestingly, only a relatively small cohort (approximately
      2%) of these genes appear to show significant changes in their levels of
      expression during ageing. Characterisation of the latter has so far revealed
      certain genes, such as glial fibrillary acidic protein, which are associated with
      the senescent phenotype. It has also revealed that the level of fos, a component
      of the AP-1 transcription factor, decreases with age, which has implications for
      AP-1 regulated genes. The differential display technique has also revealed an
      increase in mitochondrial RNA during ageing of the heart, which may be due to a
      gene dosage effect caused by the presence of increased numbers of mitochondrial
      genomes in myocytes in old age. The differential display technique therefore
      appears to offer a powerful tool for identifying genes which contribute to the
      emergence of a senescent phenotype.

PMID- 9593315
TI  - Enhanced expression of mitochondrial genes in senescent endothelial cells and
      fibroblasts.
AB  - It has been suggested that some mitochondrial genes are important in cellular
      senescence. In order to identify the mitochondrial genes that are involved in
      cellular senescence, we have constructed a cDNA library from senescent human
      vascular endothelial cells and isolated 86 senescence-specific cDNA clones by
      differential screening. Among the clones, we identified four distinct
      mitochondrial genes including NADH dehydrogenase subunit 2 (ND2), ND3, ATPase 6
      and 16S ribosomal RNA. We then compared the levels of expression of these genes
      in young and senescent cells by using two endothelial and two fibroblast cell
      strains. Northern blot and slot blot hybridization confirmed that the expression
      levels of ND3, ATPase 6 and 16S rRNA were elevated in senescent cells of all four
      strains. The expression level of ND2 was also elevated during cellular senescence
      in three of the four strains. Because mitochondria are actively involved in
      oxidative phosphorylation and respiratory functions, the altered expression
      levels of these genes may participate in aging processes.

PMID- 9593316
TI  - Studies on the life prolonging effect of food restriction: glutathione levels and
      glyoxalase enzymes in rat liver.
AB  - Cytosolic and mitochondrial levels of glutathione (GSH) as well as the activities
      of glyoxalase I (GI) and glyoxalase II (GII), GSH-dependent enzymes involved in
      the detoxification of 2-ketoaldehydes, were investigated in the liver of ad
      libitum (AL) fed and food restricted (FR) rat during aging. Both cytosolic and
      mitochondrial GSH level was lower in old than in adult AL fed rats. Food
      restriction did not prevent this decrease, but its extent was attenuated
      considering the cytosolic GSH. As regards the mitochondrial GSH, its content was
      higher in adult FR animals than in the age-matched AL fed ones. Thus, the
      subsequent age-dependent decrease of GSH, occurring also in FR animals, resulted
      in a thiol concentration not different from that observed in young and adult AL
      fed animals. Considering the enzymatic activities, cytosolic GI decreased in old
      rats irrespective of diet, whereas GII activity remained constant in all the
      experimental groups. The higher glutathione content found in both cellular
      compartments of old FR rats as compared to the old AL fed ones, could help to
      explain the life prolonging effect of FR treatment. Moreover, the observation
      that the activity of glyoxalases was not influenced by food restriction does not
      necessarily mean that the cells of diet-conditioned animals are scarcely
      protected against the toxic effect of methylglyoxal. Indeed, the production of
      this compound should be lower in FR animals as compared to AL fed ones, due to
      the lower level serum glucose concentration during the life span of the former
      with respect to the latter group.

PMID- 9593317
TI  - Age-related changes in adenylyl cyclase activity in rat aorta membranes.
AB  - Blood vessels from aged animals and humans have impaired relaxation and cAMP
      production to beta-adrenergic stimulation. Direct activators of adenylyl cyclase
      (AC) such as forskolin are not affected. We hypothesized that analogous findings
      would occur in membrane preparations. Aortic media membrane preparations from
      Fischer 344 rats of four age groups (6 weeks to 24 months) were studied. Basal AC
      activity increased significantly with age. Forskolin-stimulated activity compared
      to basal tended to be greater in the 6-week and 6-month preparations compared to
      the 12- and 24-month preparations. AC activity was assessed in the presence of
      the G protein activators (GTP, GppNHp, NaF). There was no age-related decrease in
      responsiveness. The receptor agonists isoproterenol (beta-adrenergic), and PGE-1
      (prostaglandin), were studied. There was no significant age-related change in
      responsiveness over basal activity to either of these agonists. There was a
      slight, but significant increase in the isoproterenol responsiveness over GTP
      responsiveness in the 6-week-old animals which also approached significance in
      the 6-month-old animals, but was not seen in the 12- and 24-month-old animals.
      These data suggest that using a membrane system to assess age-related changes in
      beta-adrenergic responsiveness in vascular smooth muscle does not retain the
      robust differences seen in whole vessels.

PMID- 9593318
TI  - Effect of the long-term feeding of dietary lipids on the learning ability, fatty
      acid composition of brain stem phospholipids and synaptic membrane fluidity in
      adult mice: a comparison of sardine oil diet with palm oil diet.
AB  - The effect of 12 month feeding of 5% palm oil or sardine oil diet on the maze
      learning ability, fatty acid composition of brain stem phospholipids and synaptic
      membrane fluidity in mice was studied. The time required to reach the maze exit
      and the number of times that a mouse strayed into blind alleys in the maze were
      measured three times every 4 days. The time and number of mice fed on the sardine
      oil diet were less than those of animals fed on the palm oil diet in the first
      and second trials. The results of fatty acid composition analysis of brain stem
      phosphatidylethanolamine showed that the percentage of docosahexaenoic acid
      (22:6, n-3; DHA) was higher, but the arachidonic acid (20:4, n-6; AA) and
      docosatetraenoic acid (22:4, n-6; DTA) were lower in the sardine oil diet fed
      mice than in the palm oil diet fed-animals. Moreover, the microviscosity of the
      synaptic plasma membrane in the sardine oil diet group was lower than that in the
      palm oil diet group. These results suggest that the adult mice fed on the sardine
      oil diet for a long period maintain higher levels of docosahe xaenoic acid in
      brain phospholipids, synaptic membrane fluidity and maze-learning ability than
      animals fed on the palm oil diet.

PMID- 9593319
TI  - Localization of Na,K-ATPase activity in developing rat distal colon: role of
      corticosteroids.
AB  - The role of corticosteroids in the development of Na,K-ATPase and its
      distribution along the crypt base-colonic surface was investigated in suckling,
      weanling and adult rats using a biochemical and a histochemical approach. The
      cerium-based histochemical method for detection of ouabain-sensitive K+-dependent
      p-nitrophenylphosphatase (K-NPPase) component of the Na,K-ATPase complex was used
      to localize Na,K-ATPase in the epithelium. The activity of Na,K-ATPase was very
      low 2 days after birth and increased to a maximum in adulthood. Mature surface
      colonocytes and immature cells at the crypt base were similarly reactive and the
      reaction product was decreased by the addition of ouabain and inhibited by
      omission of K+. Adrenalectomy decreased colonic Na,K-ATPase activity in surface
      and deep crypt cells of suckling, weanling and adult animals. Mineralocorticoids
      (deoxycorticosterone acetate, DOCA) restored the Na,K-ATPase activity both in
      surface and crypt cells of adrenalectomized weanling rats and the effect of DOCA
      was inhibited by the mineralocorticoid receptor antagonist, spironolactone.
      Physiological doses of glucocorticoids (dexamethasone) stimulated Na,K-ATPase
      activity in surface colonocytes of adrenalectomized weanling rats;
      supraphysiological doses restored Na,K-ATPase probably via cross-over into
      mineralocorticoid receptors both in surface and crypt cells. High dietary Na+
      intake during the weaning period reduced the reaction product to the level
      detected in adrenalectomized rats. The distribution of Na, K-ATPase activity in
      the epithelium of adrenalectomized rats with substitutional replacement hormone
      therapy was the same as in control animals or, in some animals, the surface
      absorptive epithelium exhibited a stronger reaction than the crypt cells.
      Similarly, the surface colonocytes of adult rats kept on a low-salt diet showed a
      stronger reaction than the crypt cells. These data indicate that postnatal
      development of Na,K-ATPase is regulated predominantly by aldosterone and that
      both surface and crypt cells are responsive to mineralocorticoids. Surface cells
      are also responsive to glucocorticoids.

PMID- 9593320
TI  - The role of endothelin in the age dependent increase in renal vascular resistance
      in the rat kidney.
AB  - Endothelin (ET) is a powerful vasopressor agent that is activated in a number of
      pathophysiologic states where renal perfusion is reduced. Since renal
      vasoconstriction occurs as part of renal aging, we investigated the possibility
      that ET may be activated in the old kidney. These experiments involved acutely
      blocking endogenous ET with Bosentan (a non-peptide mixed antagonist to both ET
      receptor types ETA and ETB), in Sprague-Dawley male rats of various ages: young
      (4 5 months), middle-aged (12-13 months) and old (19-20 months). Experiments were
      performed in chronically catheterized, conscious rats, studied under unstressed
      conditions. Renal hemodynamics and sodium excretion were measured before and
      during acute ET receptor blockade. In all three age groups, Bosentan had no
      effect on glomerular filtration rate (GFR), renal plasma flow (RPF), renal
      vascular resistance (RVR), blood pressure (BP) or urine flow. Sodium excretion
      increased significantly with Bosentan but the natriuresis was similar in rats of
      all ages. These results suggest that ET does not contribute to the renal
      vasoconstriction of the old rat kidney.

PMID- 9593321
TI  - Epigenetic control of programmed cell death: inhibition by 5-azacytidine of 1,25
      dihydroxyvitamin D3-induced programmed cell death in C6.9 glioma cells.
AB  - In mammalian DNA cytosine methylation occurs specifically at CpG dinucleotide.
      Although the full array of function of DNA methylation is yet to be elucidated,
      it is well established that DNA methylation is an important mechanism involved in
      gene expression, DNA replication and cancer. Rat glioma C6.9 cells undergo
      programmed cell death (PCD) after treatment with 1,25-dihydroxyvitamin D3 (1,25
      D3). Hence, these cells were used to study whether DNA methylation was involved
      in the control of PCD. We found that 1,25-D3-mediated PCD of C6.9 cells was
      suppressed by exposure of the cells to the DNA demethylating agents 5-azacytidine
      (5-AzaC) and 5-aza-2'-deoxycytidine. This effect remains detectable several cell
      divisions following removal of 5-AzaC and, therefore, involves DNA methylation as
      an epigenetic regulatory mechanism of PCD. Accordingly, internucleosomal
      fragmentation, a feature of apoptosis that is detected in 1,25-D3-treated cells,
      is no longer observable after treatment of these cells with 5-AzaC. However, 5
      AzaC does not totally suppress the responsiveness of C6.9 cells to 1,25-D3 since
      the induction of the c-myc gene remains unaffected. These results suggest that a
      change in DNA methylation pattern could suppress 1,25-D3-mediated PCD through the
      expression of previously hypermethylated genes such as proto-oncogenes with death
      repressor activity, endogenous virus sequences or even genes inducing change in
      the differentiated state of these cells.

PMID- 9593323
TI  - Impaired succinic dehydrogenase activity of rat Purkinje cell mitochondria during
      aging.
AB  - The perikaryal Purkinje cell mitochondria positive to the copper ferrocyanide
      histochemical reaction for succinic dehydrogenase (SDH) have been investigated by
      means of semiautomatic morphometric methods in rats of 3, 12 and 24 months of
      age. The number of organelles/microm3 of Purkinje cell cytoplasm (Numeric
      density: Nv), the average mitochondrial volume (V) and the mitochondrial volume
      fraction (Volume density: Vv) were the ultrastructural parameters taken into
      account. Nv was significantly higher at 12 than at 3 and 24 months of age. V was
      significantly decreased at 12 and 24 months of age, but no difference was
      envisaged between adult and old rats. Vv was significantly decreased in old
      animals vs. the other age groups. In young and old rats, the percentage of
      organelles larger than 0.32 microm3 was 13.5 and 11%, respectively, while these
      enlarged mitochondria accounted for less than 1% in the adult group. Since SDH
      activity is of critical importance when energy demand is high, the marked
      decrease of Vv supports an impaired capacity of the old Purkinje cells to match
      actual energy supply at sustained transmission of the nervous impulse. However,
      the high percentage of enlarged organelles found in old rats may witness a
      morphofunctional compensatory response.

PMID- 9593322
TI  - Down's syndrome, ageing and fragile sites.
AB  - Fragile sites have been interesting for mapping chromosomal regions involved in
      disease and ageing. The chromosomal fragile site expression from 38 Down's
      syndrome (DS) individuals aged 0-48 years was investigated in blood peripheral
      lymphocytes. Fragile sites were statistically characterized as the minimum
      expected number of lesions per band based on a Poisson distribution. The results
      showed that the fragile site 2q11 was associated with the DS condition and
      fragile sites 5q31, 6p21 and 9q12 with ageing in DS subjects. Fragility in 6p21
      has also been associated with Alzheimer's disease patients.

PMID- 9593324
TI  - The size of the subpopulation susceptible to malignant neoplasm of the brain.
AB  - A decline of mortality dependence on age from the exponential relation is
      observed for some diseases. This decline could be explained by the existence of
      an inherently susceptible population subset which is depleted faster than the
      general population. A model is presented which describes this situation using
      malignant neoplasm of the brain. The model assumes that only those who are
      members of the subset can die of malignant neoplasm of the brain. This model was
      used to fit the actual mortality curve of malignant neoplasm of the brain for
      women and men in the USA in 1979. The size of this subset equalled one of two
      parameters used to fit the actual data. The decline of mortality dependence upon
      age can be explained by this model. The size of the subpopulation is 0.390% for
      men and 0.417% for women. The theoretical curves resulting from that model
      capture the actual mortality due to malignant neoplasm of the brain.

PMID- 9593325
TI  - Treatment of seizures in patients with learning disabilities.
AB  - People with learning disabilities commonly have seizures. Combined
      electroencephalogram and video investigations improve diagnostic accuracy, while
      neuroimaging may indicate a role for surgery. When epilepsy is diagnosed,
      individually tailored care is necessary. Rational antiepileptic drug use is
      advocated, with emphasis upon the newer agents due to their better tolerability
      and ease of use. Regular clinical review will prevent over-medicating. Although
      an optimistic approach can now be adopted, future developments require a more
      solid evidence base together with a rationality to all aspects of care, including
      drug therapy, carer education, closer collaboration among specialists, and mutual
      skill awareness of all involved.

PMID- 9593326
TI  - Antiepileptic drug therapy in the elderly.
AB  - Populations are aging, and the incidence of epilepsy is increased in the elderly
      population. These demographic facts emphasize the importance of understanding the
      use of antiepileptic drugs in older patients. Healthy elderly have expected
      alterations in renal blood flow, hepatic volume and function, and alterations in
      fat-to-lean ratio of body composition. All of these changes make elderly patients
      vulnerable to dose-related adverse effects of the standard antiepileptic drugs.
      Newly developed compounds without enzyme induction effects and renal routes of
      excretion may be more favorable for use in elderly patients.

PMID- 9593327
TI  - Chemopreventive activity of oltipraz.
AB  - The antischistosomal agent oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3
      thione] has been shown to inhibit chemically induced carcinogenesis in a variety
      of animal models. Of greatest interest is its unique ability to protect several
      target organs from structurally diverse carcinogens. Molecular and biochemical
      studies suggest that oltipraz affords cellular protection by inducing the
      expression of a battery of Phase II detoxification enzymes. Induction of
      glutathione S-transferase, gamma-glutamylcysteine synthetase and DT-diaphorase
      has been observed in human tissues following the administration of a single oral
      dosage of oltipraz. Preclinical and clinical data continue to support the
      development of oltipraz as a chemopreventive agent for clinical usage.

PMID- 9593328
TI  - Molecular mechanisms of interferon resistance mediated by viral-directed
      inhibition of PKR, the interferon-induced protein kinase.
AB  - The interferon (IFN)-induced cellular antiviral response is the first line of
      defense against viral infection within an animal host. In order to establish a
      productive infection, eukaryotic viruses must first overcome the IFN-induced
      blocks imposed on viral replication. The double-stranded RNA-activated protein
      kinase (PKR) is a key component mediating the antiviral actions of IFN. This IFN
      induced protein kinase can restrict viral replication through its ability to
      phosphorylate the protein synthesis initiation factor eukaryotic initiation
      factor-2 alpha-subunit and reduce levels of viral protein synthesis. Viruses,
      therefore, must block the function of PKR in order to avoid these deleterious
      antiviral effects associated with PKR activity. Indeed, many viruses have
      developed effective measures to repress PKR activity during infection. This
      review will focus primarily on an overview of the different molecular mechanisms
      employed by these viruses to meet a common goal: the inhibition of PKR function,
      uncompromised viral protein synthesis, and unrestricted virus replication. The
      past few years have seen exciting new advances in this area. Rather unexpectedly,
      this area of research has benefited from the use of the yeast system to study
      PKR. Other recent advances include studies on PKR regulation by the herpes
      simplex viruses and data from our laboratory on the medically important hepatitis
      C viruses. We speculate that IFN is ineffective as a therapeutic agent against
      hepatitis C virus because the virus can effectively repress PKR function.
      Finally, we will discuss briefly the future directions of this PKR field.

PMID- 9593329
TI  - Smads are the central component in transforming growth factor-beta signaling.
AB  - Until recently, little was known about how transforming growth factor (TGF)-beta
      signals are transduced to the nucleus. With the discovery of the Smad proteins
      initially in Drosophila and C. elegans, the unraveling of the pathway has begun.
      Nine different vertebrate members also have been reported, indicating that Smads
      are a conserved component of the TGF-beta pathway. Currently, there are three
      functional classes of Smads. Class I Smads are phosphorylated by TGF-beta
      receptors and move to the nucleus. The Class II Smads function with Class I
      Smads, while Class III Smads antagonize the function of Class I Smads. New
      evidence shows that Smads bind specific DNA sequences and induce transcription of
      downstream target genes, thus placing the Smads at the center of the TGF-beta
      signaling pathway.

PMID- 9593330
TI  - The effect of acute kainic acid treatment on dopamine D2 receptors in rat brain.
AB  - Acute exposure to kainic acid (KA) induces neurochemical changes in dopaminergic
      systems in the brain and the aim of the present study was to investigate the
      acute toxicity of KA upon dopamine D2 receptors. Adult rats were injected
      intraperitoneally with either saline or 16 mg/kg KA. Brains were removed after 4
      h. Membrane homogenates were prepared from seven brain regions and in addition,
      frozen coronal sections were sectioned for comparative quantitative
      autoradiographic analysis. Dopamine D2 receptors were characterised by saturation
      studies using [125I]iodosulpiride, [3H]raclopride and [3H]spiperone. KA produced
      a 2-fold decrease in receptor affinity for [125I]iodosulpiride and a 2-fold
      increase in receptor density in all regions studied except striatum. Quantitative
      autoradiography with [125I]iodosulpiride showed similar increases in D2 labelling
      following KA except in caudate putamen, nucleus accumbens and olfactory tubercle.
      In contrast, there was no change in [3H]spiperone binding in whole brain minus
      striatum nor in striatum alone after KA treatment. KA produced a significant
      increase in Bmax for [3H]raclopride in whole brain minus striatum and in striatum
      alone with minimal changes in affinity. These findings demonstrate acute changes
      in rat brain dopamine D2 receptors labelled with [125I]iodosulpiride and
      [3H]raclopride but not [3H]spiperone after KA treatment predominantly in extra
      striatal regions.

PMID- 9593331
TI  - Substance P receptor-expressing neurons in the medullary and spinal dorsal horns
      projecting to the nucleus of the solitary tract in the rat.
AB  - By using substance P receptor (SPR) immunofluorescence histochemistry combined
      with fluorescent retrograde labeling, we examined the distribution of the
      trigeminal and spinal neurons with SPR-like immunoreactivity (-LI) projecting to
      the nucleus of the solitary tract in the rat. After injection of Fluoro-Gold (FG)
      into the nucleus of the solitary tract, FG-labeled neurons showing SPR-LI were
      mainly seen in lamina I of the medullary and spinal dorsal horns, lamina V and
      the lateral spinal nucleus of the spinal cord. The present results suggest that
      the trigeminal and spinal neurons with SPR-LI, especially those in lamina I may
      be involved in the transmission of somatic and/or visceral nociceptive
      information from the medullary and spinal dorsal horns to the nucleus of the
      solitary tract.

PMID- 9593332
TI  - Substance P receptor (NK1)-immunoreactive neurons projecting to the
      periaqueductal gray: distribution in the spinal trigeminal nucleus and the spinal
      cord of the rat.
AB  - Substance P receptor (SPR)-immunoreactive neurons projecting to the
      periaqueductal gray (PAG) were examined in the rat spinal trigeminal nucleus and
      spinal cord by a retrograde tracing method combined with immunofluorescence
      histochemistry. After injection of Fluoro-gold (FG) into the PAG, SPR
      immunoreactive neurons labeled with FG were observed mainly in the lateral spinal
      nucleus and lamina I of the medullary and spinal dorsal horns and additionally in
      laminae V and X of the spinal cord.

PMID- 9593333
TI  - Membrane properties of dissociated trigeminal mesencephalic neurons of the adult
      rat.
AB  - Electrophysiological properties of pseudounipolar trigeminal mesencephalic (Me5)
      neurons, dissociated from the rat brain, were studied under current-clamp
      conditions using the whole-cell configuration. Almost all Me5 neurons (37/38,
      97%) exhibited a rapid adaptation in response to long depolarizing current
      pulses. Another firing type, slowly-adapting, was observed in only 3% of neurons
      (1/38). Most Me5 neurons (42/43) generated an overshooting action potential
      without a hump on the falling phase, and the remaining neuron (1/43) showed an
      action potential with a small hump. The action potential of Me5 neurons was
      reversibly blocked by 1 microM tetrodotoxin (TTX) or by removing Na+ from the
      bathing medium. When the outward K+ current was suppressed, two types of Ca2+
      spikes were revealed. According to characteristic thresholds and sensitivity to
      inorganic (Ni2+, Cd2+) and organic (nifedipine, omega-conotoxin GVIA) Ca2+
      channel blockers, these Ca2+ spikes were identified as T-type LTS (low-threshold
      spike) and L-type HTS (high-threshold spike). Also, a time-dependent inward
      rectification was observed in all Me5 neurons. It is concluded that the majority
      of Me5 neurons are of the rapidly-adapting type and generate a TTX-sensitive Na+
      spike with negligible contribution of Ca2+, showing that the electrophysiological
      properties of Me5 neurons are more similar to those of CNS neurons than to those
      of PNS ganglion cells which have similar morphological features to Me5 neurons.

PMID- 9593334
TI  - Crossing inputs of the superior laryngeal nerve afferents to medullary swallowing
      related neurons in the cat.
AB  - To understand the neural mechanism for generation of synchronous activity on both
      sides during swallowing, we examined the convergence of inputs from the bilateral
      superior laryngeal nerves (SLNs) in the urethane-anesthetized cat medulla and we
      also examined the changes in swallowing outputs after a longitudinal brain-stem
      split in decerebrate cats. Twenty-six (31%) of 84 swallowing-related neurons
      (SRNs) that were oligosynaptically activated by ipsilateral SLN stimulation and
      recorded mostly in the reticular formation received contralateral inputs, which
      were confirmed by orthodromic spike responses (n = 16) or were detected as
      subliminal facilitatory or inhibitory inputs (n = 10) using conditioning-test
      stimuli. The rate of convergence of inputs from bilateral SLNs in these SRNs was
      significantly higher than that (4%) in the SRNs that were regarded as sensory
      relay neurons in the nucleus tractus solitarius (NTS). The SRNs receiving signals
      from the contralateral SLN were located diffusely from the NTS and the adjacent
      reticular formation to the nucleus ambiguus (NA) and the reticular formation
      dorso-medial to the NA. A midsagittal split from 3 mm caudal to 6 mm rostral to
      the obex could change symmetrical swallowing to unilateral swallowing. Thus the
      crossing projections to the contralateral SRNs appear to contribute to
      symmetrical swallowing.

PMID- 9593335
TI  - Segmental distribution of the motoneurons innervating trunk muscles in the spinal
      cord of the cat and rat.
AB  - The current progress in developmental biology suggests a genetically stable
      peripheral pathway formation. However, this may be incompatible with the
      variations or anomalies observed in the segmental origins of motor nerves in the
      mammals including the human. For the consideration of the causes raising this
      inconsistency, we examined the distribution of motoneurons for the serratus
      dorsalis cranialis muscle of the cat using a retrograde labeling method because
      this muscle consists of segmentally-arranged parts which receive segmental dual
      innervation. Consequently, the distribution of the labeled motoneurons for one
      part spread throughout the full extent of two spinal cord segments, while the
      distributions for the intercostal muscles in the cat and rat were segmental and
      in accordance with each spinal cord segment. This may indicate the more precise
      correspondence between the spinal nerve segments and the distribution of
      motoneurons projecting axons through them. We think, therefore, that segments of
      the spinal nerves supplying a given target exactly indicate the segmental levels
      of supplying motoneurons and suggest the segments of somites from which
      primordial cells of the target migrate.

PMID- 9593336
TI  - Augmentation of postural muscle tone induced by the stimulation of the descending
      fibers in the midline area of the cerebellar white matter in the acute
      decerebrate cat.
AB  - In a reflexively standing acute decerebrate cats, the cerebellar white matter was
      systematically stimulated and the effects on the level of postural muscle tone
      were studied. A stimulating microelectrode was placed systematically at 0.1-0.5
      mm increments from H + 2 to H - 2 at levels ranging from P7.0 to P8.0
      rostrocaudally and mediolaterally from LR0 to L1.5 or R1.5. Stimuli delivered to
      the restricted region of the cerebellar white matter along its midline resulted
      in simultaneous and bilateral augmentation of tonic activities in the neck,
      lumbar back, fore- and hindlimb extensor muscles along with increased levels in
      the forces exerted by each of the left and the right fore- and hindlimbs.
      Effective stimulus regions were located in the cerebellar white matter rostral
      and ventral to the most rostral part of the fastigial nucleus. Microinjection of
      a retrograde neural tracer, cholera-toxin b subunit conjugated horseradish
      peroxidase (CTb-HRP), into the lesioned effective stimulus sites resulted in a
      retrograde labeling of cells in the fastigial nuclei, bilaterally. All these
      results suggest that the augmentation of postural muscle tone was evoked by a
      selective activation of fastigiofugal fibers which course through the 'hook
      bundle'.

PMID- 9593337
TI  - The effect of neuronal perturbation on the uptake of [18F]2-fluoro-2-deoxy-D
      glucose in brain slices of the rat.
AB  - The positron-emitting radionuclide 18F was used to label 2-fluoro-2-deoxy-D
      glucose producing [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG), and subsequently
      applied to sagittally-sectioned brain slices of the rat to evaluate the activity
      of neurons for up to 7 h in living brain slices. The amount of [18F]FDG uptake,
      which is proportional to the activity of neurons, was monitored every 20 min in
      five representative brain regions: frontal cortex, caudate-putamen, thalamus,
      hippocampus and cerebellum. The uptake of [18F]FDG linearly increased with time
      in these areas, showing constant glucose utilization. The rate of uptake was
      reversibly decreased by tetrodotoxin (TTX) regardless of brain region, but some
      uptake was insensitive to TTX. There was a tendency for the uptake to be
      decreased in Ca2+-free, 5 mM Mg2+ (2 mM EGTA) solution, suggesting some remaining
      functional synapses. Thus in sagittally-sectioned brain slices, most glucose
      metabolism is dedicated to neuronal firings and some metabolism to synaptic
      activities and to other functions of neurons and glial cells. When Cd2+ was
      applied to brain slices at 0.1-1 mM, the curve of [18F]FDG uptake irreversibly
      declined, indicating its toxic effect rather than its blocking action of
      transmitter release at synapses. The cerebellum was the most sensitive to Cd2+,
      and the caudate-putamen was the least sensitive. The present method, therefore,
      can be also used as a rapid examination system for checking neurotoxicity of
      substances.

PMID- 9593338
TI  - Role of NMDA receptors in the emotional memory associated with neuroendocrine
      responses to conditioned fear stimuli in the rat.
AB  - Behavioral experiments have shown that the N-methyl D-aspartate (NMDA) subclass
      of glutamate receptor plays an important role in acquisition of emotional memory.
      Exposure of a rat to conditioned fear stimuli suppresses vasopressin (VP) release
      and augments oxytocin (OT) or prolactin (PRL) release from the pituitary. Present
      experiments aimed at investigating the effect of intraperitonially administered
      MK-801, an antagonist of NMDA receptor on the emotional memory associated with
      the suppressive VP and the augmentative OT or PRL responses to conditioned fear
      stimuli in male rats. MK-801 injected 30 min before training impaired the VP, OT
      and PRL responses to the testing fear stimuli. The antagonist injected after
      training, however, did not block the responses. MK-801 administered before
      testing impaired the previously acquired VP, OT and PRL responses to conditioned
      fear stimuli. In the experiments with non-associatively applied fear stimuli, MK
      801 did not block the VP, OT or PRL response. In the experiments with novel
      environmental stimuli, MK-801 did not impair VP, OT or PRL responses. The results
      suggest that an activation of NMDA receptors are required to acquire and recall
      but not to consolidate or retain the emotional memory associated with VP, OT and
      PRL responses to conditioned fear stimuli.

PMID- 9593339
TI  - Quality control practices for calcium, cholesterol, digoxin, and hemoglobin: a
      College of American Pathologists Q-probes study in 505 hospital laboratories.
AB  - OBJECTIVE: To assess quality control (QC) practices and their impact on hospital
      laboratories using the College of American Pathologists (CAP) Q-Probes process.
      DESIGN: Self-directed data gathering, using a questionnaire to determine QC
      practices, data input forms for 6 months retrospective quality control use and
      run failure rates, and input forms for 3 months prospective data concerning QC
      failure rates and corrective steps taken. Participants submitted data for four
      analytes: calcium, cholesterol, digoxin, and hemoglobin. PARTICIPANTS:
      Laboratories enrolled in the 1994 CAP Q-Probes program. MAIN OUTCOME MEASURES:
      Retrospective and prospective QC failure rates compared with QC protocols and the
      corrective steps. RESULTS: Five hundred five hospital laboratories returned
      various components of the study. Median retrospective run rejection rates per
      1000 runs: calcium, 4.3; cholesterol, 3.6; digoxin, 4.3; and hemoglobin, 2.4.
      Corresponding median prospective run rejection rates per 1000 runs: calcium, 5.8;
      cholesterol, 5.6; digoxin, 6.5; and hemoglobin, 3.6. Participants resolved most
      out-of-control events in less than 20 minutes, with no patient samples repeated.
      More than 95% of the time, participants resolved out-of-control events simply by
      repeating controls. Most participants used a single control rule based on a
      target mean plus or minus a multiple of the standard deviation. A few
      laboratories used multirule systems. CONCLUSIONS: Current testing methods yield
      few out-of-control events, which usually are resolved rapidly, with little impact
      on laboratory operation. We recommend modification and simplification of
      laboratory QC practices to decrease false rejection rates and to use modern
      instrumentation more efficiently.

PMID- 9593340
TI  - Pathology information systems: data mining leads to knowledge discovery.
AB  - Information systems in pathology provide opportunities for pathologists and
      clinical laboratory scientists to impact both clinical care and modern research
      agendas. The paradigm shift in health care from individualized care to population
      based and standardized delivery systems has created both of these opportunities.
      In research, pathology information systems can provide key databases for health
      services research and new informatics-based approaches to database research. The
      latter is characterized by utilization of pathology databases for data mining to
      discover new patterns that provide new knowledge. The multidisciplinary knowledge
      discovery and data mining program at the University of Alabama at Birmingham
      focuses on this health care application, which has the potential to make a major
      impact on health care research and delivery.

PMID- 9593341
TI  - Clinical utility of cardiac valve Gram stain and culture in patients undergoing
      native valve replacement.
AB  - OBJECTIVES: To determine if routine cardiac valve culture is useful in diagnosing
      clinically unsuspected infective endocarditis in patients undergoing native valve
      replacement, to see if false-positive culture results have a deleterious effect
      on patient care, and to determine if microbiology and histopathology can be used
      to differentiate partially treated and untreated infective endocarditis from
      valve contamination. DESIGN: Case series. SETTING: Tertiary-care teaching
      hospital with 1125 beds. PATIENTS: Forty-eight patients with culture-positive
      cardiac valves after native valve replacement. RESULTS: A single unsuspected case
      of endocarditis was disclosed by microbiology over a 5-year period.
      Histopathology in this case was also positive, however, and the diagnosis should
      have been suspected clinically. Eighty-three percent of positive cultures were
      the result of contamination over an 18-month period; results were disregarded
      appropriately by clinicians. Clinical context or histopathology was required to
      categorize microorganisms correctly as pathogens or contaminants; only the
      presence of organisms on Gram stain had a good predictive value for endocarditis.
      CONCLUSION: Routine valve cultures in patients undergoing native valve
      replacement are not warranted. Although false-positive culture results had no
      deleterious effects on patient care in this study, misinterpretation of such
      results could lead to overtreatment. Microbiology results alone are not
      sufficient to distinguish endocarditis from contamination.

PMID- 9593342
TI  - Relationship between the effector T-cell response and viremia in symptomatic
      chronic hepatitis C.
AB  - OBJECTIVE: The purpose of this study was to assess the relationship between
      hepatitis C virus (HCV) viremia, HCV genotype, histologic activity index, and
      intrahepatic densities of immunocompetent lymphoid cells in chronic hepatitis C.
      METHOD: Liver biopsy specimens from patients with chronic hepatitis and anti-HCV
      antibodies, 5 with low-level HCV viremia and 26 with high-level HCV viremia, were
      studied. Sections of snap-frozen specimens were immunostained with monoclonal
      antibodies directed against different subsets of B cells, follicular reticulum
      cells, and T cells, including CD45RA-naive cells and CD45RO-primed cells. The
      densities of each subset of lymphoid cells were calculated with a computerized
      image analyzer. Hepatitis C virus RNA was measured with a quantitative branched
      DNA signal amplification assay, and HCV genotypes were determined with the line
      probe assay. RESULTS: A statistical correlation was found between the level of
      HCV viremia and the histologic activity index (P = .002). There were also
      significant correlations between the densities of CD3+ T cells and CD45RO+-primed
      cells in the liver and the histologic activity index and (P = .024 and P = .005,
      respectively), and significant correlations were found between the densities of
      CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD45RO+-primed cells and HCV
      viremia (P = .005, P = .03, P = .03, and P = .02, respectively). Whatever the
      viremia status, CD45RO-primed cells were more numerous than CD45RA-naive cells in
      lobules and portal tracts. The CD45RO/CD45RA ratio was significantly higher when
      intraportal lymphoid aggregates were present. Eight patients were infected with
      genotype 1b, and 11 were infected with genotype 3b. There were no statistical
      differences in the histologic activity index, viremia, and density of
      immunocompetent cells in the liver between these two HCV genotypes. CONCLUSIONS:
      The results of this study suggest that the density of antigen-primed effector T
      cells in the liver of symptomatic patients with chronic hepatitis C is adapted to
      HCV viremia but is independent of the occurrence of genotypes 1b or 3a, the most
      frequent genotypes found in France.

PMID- 9593343
TI  - Ultrastructure of atypical (teratoid) sporogonial stages of Enterocytozoon
      bieneusi (Microsporidia) in naturally infected rhesus monkeys (Macacca mulatta).
AB  - OBJECTIVE: To demonstrate the ultrastructural features of normal and atypical
      (teratoid) developmental stages of Enterocytozoon bieneusi in naturally infected
      rhesus monkeys (Macacca mulatta). DESIGN AND METHODS: Two rhesus monkeys with
      chronic simian immunodeficiency virus infection developed naturally acquired
      microsporidian infections. The gallbladder had a high parasite burden and was
      evaluated by transmission electron microscopy. The microsporidian agent was
      confirmed as E bieneusi by polymerase chain reaction. RESULTS: In addition to
      normal sporogonial plasmodia and spores of E bieneusi, abnormal teratoid
      structures were noted. These structures were greatly enlarged (up to 10 microm)
      and were surrounded by an electron-dense exospore and electron-lucent endospore
      typical of mature spores. Unlike mature spores, the abnormal structures contained
      multiple nuclei and polar tubes in varying proportions, which were reminiscent of
      sporogonial plasmodia. CONCLUSIONS: These teratoid structures represent aberrant
      sporogonial stages, a result of defective maturation in which abnormal
      cytokinetic replication of organelles occurs, and normal development into
      uninucleate sporoblasts and spores is inhibited. This leads to the development of
      teratoid stages having mature spore walls, but containing multiple sets of nuclei
      and polar tubes, unusual polyribosomal arrays and vacuoles, or persistent
      cleavage. The biological significance of these atypical spores is unknown, but it
      is evident that they develop in the absence of antimicrosporidian drugs in
      extraintestinal tissues from nonhuman primates. Teratoid spores of E bieneusi
      should not be misinterpreted as another microsporidian species or confused with
      other pathogenic protozoa, nor should their presence be misconstrued as evidence
      of antimicrosporidian drug efficacy or toxicity.

PMID- 9593344
TI  - Activated protein C resistance assay performance: improvement by sample dilution
      with factor V-deficient plasma.
AB  - OBJECTIVE: To evaluate a modification of a commercially available reagent kit
      (COATEST APC Resistance Kit) for functional activated protein C (APC) resistance
      testing, and to determine the ability of the modified assay to demonstrate APC
      resistance in patients receiving warfarin. DESIGN: Functional APC resistance
      testing was performed using both the first-generation COATEST APC Resistance Kit
      and a modified, or second-generation, version of the COATEST assay that uses
      predilution of the patient sample with factor V-deficient plasma. Factor V
      genotyping for APC resistance (FV R506Q) was performed using a well-characterized
      polymerase chain reaction-restriction fragment length polymorphism method.
      SETTING: University medical center. PATIENTS: Seventy-three individuals referred
      for hypercoagulability testing who were not receiving warfarin therapy and 29
      patients with a history of venous thrombosis who were receiving warfarin therapy.
      MAIN OUTCOME MEASURE: Sensitivity and specificity as determined by comparing
      functional APC resistance to the FV R506Q genotype. RESULTS: In 73 patients
      referred for hypercoagulability testing, but not receiving warfarin therapy, a
      sensitivity of 0.86 and a specificity of 0.75 were obtained with the first
      generation COATEST assay. In contrast, a sensitivity and specificity of 1.0 were
      obtained when the second-generation COATEST assay was employed. In 29 patients
      receiving warfarin, the first-generation assay exhibited a sensitivity and
      specificity of 0.88 and 0.95, respectively, whereas the sensitivity and
      specificity for the second-generation assay was 1.0. CONCLUSIONS: Predilution of
      patient plasma with factor V-deficient plasma results in improved sensitivity and
      specificity of the COATEST APC Resistance Kit, thus offering a simple
      modification to enhance APC resistance determination in the routine clinical
      laboratory setting.

PMID- 9593345
TI  - Clinicopathologic heterogeneity in hypertrophic cardiomyopathy with regard to
      age, asymmetric septal hypertrophy, and concentric hypertrophy beyond the
      pediatric age group.
AB  - BACKGROUND: To our knowledge, no histopathologic study of the differences between
      hypertrophic cardiomyopathy in different age groups or that contrasts the
      pathologic findings in the asymmetric septal hypertrophy and concentric
      hypertrophy forms of hypertrophic cardiomyopathy has been published. METHODS: The
      clinicopathologic findings of younger (< or =60 years) (n = 35) and older (>60
      years) (n = 20) patients with hypertrophic cardiomyopathy were assessed. Each
      group was subdivided into groups of patients with asymmetric septal hypertrophy
      or concentric hypertrophy. RESULTS: Among the young patients, asymmetric septal
      hypertrophy was more prevalent than concentric hypertrophy, whereas among the
      elderly patients, concentric hypertrophy was more common. Sudden death was
      prevalent only among the young. Most young patients had a mirror-image
      endocardial fibrous septal plaque, whereas most elderly patients with concentric
      hypertrophy did not. Ventricular septal myocyte disarray and intramural coronary
      artery thickening were far more marked among the young with asymmetric septal
      hypertrophy than the young with concentric hypertrophy and the elderly.
      CONCLUSIONS: Key differences exist between younger and older patients with
      hypertrophic cardiomyopathy. Much higher degrees of ventricular disarray and
      intramural coronary artery disease were noted in younger patients with asymmetric
      septal hypertrophy compared to the elderly patients and the younger patients with
      concentric hypertrophy.

PMID- 9593347
TI  - Histologic findings in patients with head and neck squamous cell carcinoma
      receiving perilymphatic natural cytokine mixture (IRX-2) prior to surgery.
AB  - OBJECTIVE: To induce tumor regression with immunotherapy and to characterize the
      histology. SETTING: National Institute of Cancerology, Mexico City, Mexico.
      PATIENTS: Thirteen patients with advanced squamous cell carcinoma of the head and
      neck region. INTERVENTION: A 21-day cycle of preoperative immunotherapy,
      including a single intravenous infusion of low-dose cyclophosphamide (300 mg/M2),
      10 daily perilymphatic injections of a natural cytokine mixture (approximately
      150 units interleukin-2 equivalence by enzyme-linked immunosorbent assay), daily
      oral indomethacin, and daily oral zinc with multivitamins. OUTCOME MEASURES:
      Pretreatment biopsies were performed to confirm the diagnosis and to characterize
      the lesion by standard pathologic criteria, including the degree of tumor
      associated lymphocytes. Clinical responses were assessed at surgery, and the
      specimen was analyzed with respect to changes in tumor morphology and lymphoid
      and inflammatory infiltration (T and B lymphocytes, plasma cells, macrophages,
      granulocytes, and giant cells). The presurgical and postsurgical characteristics
      were ascribed percentages based on a representative section. RESULTS: Prior to
      treatment, on average the biopsies demonstrated 77% solid tumor with 14% stroma
      and 9% sparse infiltration of lymphocytes. After treatment, one patient had a
      complete clinical response and showed only residual inflammatory cells and
      fibrosis. One patient had no clinical or histologic response. Of the remaining 11
      patients, 4 had partial, 6 had minor, and 1 had no response. Tumors were reduced
      an average of 41% (16% solid and 25% fragmented) and lymphoid infiltration
      increased to 45% without change in residual stroma. CONCLUSIONS: The pathologic
      changes viewed in the context of the clinical findings indicate that this
      immunotherapy protocol induces immune regression of the tumor, mediated
      predominantly by T and B lymphocytes, and thus elicits a tumor-specific immune
      reaction.

PMID- 9593346
TI  - Morphometric and electron-microscopic analyses of the effects of gonadotropin
      releasing hormone agonists on uterine leiomyomas.
AB  - OBJECTIVE: Reports on the histologic effects of gonadotropin-releasing hormone
      agonists on uterine leiomyomas provide conflicting results. Most previous studies
      used qualitative methods of analysis. Using quantitative and semiquantitative
      stereologic methods of analysis, we assessed volume density of hyalinized areas,
      cell density, nuclear volume, and cytoplasmic cross-sectional areas of smooth
      muscle cells in histologic sections and also measured diameters of collagen
      fibrils in electron micrographs of uterine leiomyomas. DESIGN: Thirty leiomyomas
      from patients treated with gonadotropin-releasing hormone agonists (10 different
      patient samples), age-matched control patients (10 different patient samples),
      and postmenopausal women (10 different patient samples) were used. Hyalinization
      was assessed using a microscope with a projection head and affixed morphometric
      grid. Cell size and density were evaluated using a video-based, computerized
      system attached to the microscope, for which morphometric ad hoc programs were
      written. Diameters of collagen fibrils were measured from electron micrographs.
      SETTING: The study was conducted in the Department of Pathology, Mount Sinai
      Medical Center, New York, NY. PATIENTS: A total of 30 patient samples were
      studied, with three groups comprising 10 samples each, including patients treated
      with gonadotropin-releasing hormone agonists, age-matched control patients, and
      postmenopausal women. RESULTS: Myomas from patients treated with gonadotropin
      releasing hormone agonists exhibited more hyalinization, greater cell density,
      slightly smaller cell sizes, and larger collagen fibrils than those of age
      matched control patients and postmenopausal women. CONCLUSIONS: Shrinkage after
      treatment with gonadotropin-releasing hormone agonists is attributed to smaller
      cell size and increased collagenization in myomas.

PMID- 9593348
TI  - Collagenous fibroma (desmoplastic fibroblastoma): report of four cases and review
      of the literature.
AB  - BACKGROUND: Collagenous fibroma (desmoplastic fibroblastoma) is poorly recognized
      and may be mistaken for other benign or even malignant spindle-cell tumors of
      soft tissue because of the small number of reported cases. DESIGN: Collagenous
      fibromas resected from four adult women were studied histologically and
      immunohistochemically. RESULTS: The tumors were well-circumscribed firm masses,
      measuring from 1.0 to 13.8 cm (mean, 5.5 cm) across the greatest diameter,
      located in the subcutaneous or deep soft tissue of the shoulder, thigh, back, and
      neck. Each of the tumors was characterized by a paucicellular lesion with spindle
      and stellate-shaped fibroblastic cells embedded in a hypovascular, densely
      fibrous stroma. Mitotic figures and necrosis were not identified. One tumor
      contained dystrophic calcification and metaplastic bone, and another included
      small foci of floretlike multinucleated giant cells. Although appearing well
      demarcated on gross examination, one tumor focally infiltrated the surrounding
      skeletal muscle and adipose tissue. On immunohistochemical examination, all of
      the tumors were diffusely positive for vimentin. One tumor showed focal staining
      for alpha-smooth muscle actin, and another was partially positive for desmin, a
      staining profile that is typical of myofibroblasts. No tumor recurred during the
      follow-up periods of 67 to 108 months (mean, 93 months). CONCLUSION: Collagenous
      fibroma may be a distinctive fibrous soft-tissue tumor with benign biological
      behavior.

PMID- 9593349
TI  - NADPH diaphorase-containing nerve fibers and neurons in the myenteric plexus are
      resistant to postmortem changes: studies in Hirschsprung's disease and normal
      autopsy material.
AB  - OBJECTIVE: Nitric oxide is considered to be the most important messenger of
      inhibitory nonadrenergic, noncholinergic nerves in the enteric nervous system.
      Histochemical studies have shown that nitric oxide synthase is identical to
      reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase.
      Histochemical staining with NADPH diaphorase has been widely used to study
      nitrergic innervation of the gastrointestinal tract, but fresh tissue is
      considered a prerequisite for satisfactory results. The purposes of this study
      were to evaluate whether whole-mount specimens of human bowel obtained after
      death are suitable for histochemical staining with NADPH diaphorase and to
      compare the staining properties with those of specimens of resected bowel from
      patients with Hirschsprung's disease METHODS: Whole-mount preparations of the
      myenteric plexus were examined using NADPH diaphorase histochemical staining of
      bowel specimens obtained at autopsy from 18 pediatric subjects (31 specimens).
      Fresh tissue was also obtained from the colon of four patients with
      Hirschsprung's disease. The staining properties of postmortem specimens were
      assessed in relation to the postmortem time before fixation (<12 hours, 13-24
      hours, or 25-48 hours) and were compared with those of specimens of ganglionic
      bowel from patients with Hirschsprung's disease. Specimens of aganglionic bowel
      were also stained and examined. RESULTS: Strong NADPH diaphorase staining was
      achieved in 26 of the 31 postmortem bowel specimens, including all specimens from
      patients who underwent autopsy 25 to 48 hours after death. Staining properties
      were similar to those obtained in ganglionic bowel specimens from patients with
      Hirschsprung's disease. In aganglionic bowel the normal myenteric plexus meshwork
      was absent and was replaced by weakly staining nerve fibers. CONCLUSION:
      Histochemical staining with NADPH diaphorase is a robust technique suitable for
      use with whole-mount preparations to demonstrate nitrergic innervation in
      motility disorders such as Hirshsprung's disease. The technique may be used with
      both fresh tissue and specimens obtained up to 48 hours after death.

PMID- 9593350
TI  - Pulmonary hypertension associated with systemic lupus erythematosus:
      predominantly thrombotic arteriopathy accompanied by plexiform lesions.
AB  - We report an autopsy case of pulmonary hypertension associated with systemic
      lupus erythematosus in a 48-year-old woman. After 8-year follow-up under a
      definite diagnosis of systemic lupus erythematosus, she experienced gradually
      developing exertional dyspnea with palpitation. Her chest x-ray showed clear lung
      fields with marked cardiac enlargement. A right cardiac catheterization revealed
      a pulmonary arterial pressure of 74/30 mm Hg (mean: 47). She was treated with
      repeated plasmapheresis, oral corticosteroid, and immunosuppressant without
      improvement, and she died suddenly, 23 days after admission. Pathological
      examination revealed that small pulmonary arteries and arterioles were diffusely
      involved by florid thrombotic lesions, which were characterized by intimal
      eccentric fibrous thickening, luminal occlusion with recanalization, and
      occasional fresh thrombi. In addition, some arteries showed plexiform lesions
      coexistent with intimal thrombotic lesions. Concentric laminar intimal fibrosis
      was not seen. No significant parenchymal change was seen. Our study not only adds
      a rare case of thrombotic pulmonary hypertension associated with systemic lupus
      erythematosus, but also suggests that plexiform lesions can occur in association
      with thrombotic arteriopathy.

PMID- 9593351
TI  - Pseudoinvasive, nodular extramammary Paget's disease of the vulva.
AB  - We report a case of recurrent extramammary Paget's disease of the vulva, which
      clinically, grossly, and microscopically mimicked an invasive lesion. A 76-year
      old woman presented with recent onset of vaginal bleeding, a nodular vulvar
      lesion, and left inguinal lymphadenopathy. Following a vulvar biopsy and
      endometrial curettage, the patient underwent a total hysterectomy and bilateral
      salpingo-oophorectomy with lymph node dissection and a modified radical
      vulvectomy with left inguinal node dissection. Papillary serous adenocarcinoma
      was found involving the uterus and one right common iliac lymph node. Sections
      through the vulvar nodule revealed a marked intraepithelial proliferation, which
      resulted in a complex epidermal hyperplasia with deep invaginations. Tangential
      sections of rete pegs filled with Paget's cells and surrounded by papillary
      dermis displaced into the deep reticular dermis mimicked invasive nests of tumor
      cells. The loose fibrous tissue of the displaced papillary dermis resembled a
      desmoplastic reaction. No true stromal invasion was present, and none of the
      inguinal lymph nodes were involved by Paget's cells. The Paget's disease did not
      resemble the uterine carcinoma by histopathologic and immunohistochemical study.
      Recognition of the intraepithelial nature of Paget's disease has important
      clinical implications, inasmuch as stromal invasion can be associated with
      metastatic disease.

PMID- 9593352
TI  - Web-based pathology education.
AB  - OBJECTIVE: To develop and present computer-aided instructional resources via the
      Internet, intranets, and desktop computers to augment pathology education.
      DESIGN: World Wide Web sites available via Internet access and a CD-ROM for
      intranets. SETTING: The University of Utah School of Medicine, Salt Lake City.
      RESULTS: A comprehensive set of gross and microscopic images with text, along
      with interactive examination questions, has been developed and placed on World
      Wide Web servers. A CD-ROM has been developed for use with intranets and
      individual desktop computers. CONCLUSIONS: Web-based delivery of computer-aided
      instruction is an efficient means of enhancing courses for students studying
      pathology. Both Internet and CD-ROM delivery of educational resources provide
      flexible access to study materials. Teaching faculty can easily generate and edit
      web-based materials for efficient resource management. Student performance has
      been enhanced.

PMID- 9593353
TI  - Geographical information systems (GIS), gimmick or tool for health district
      management?

PMID- 9593354
TI  - Traditional medicine to DNA vaccines: the advance of medical research in West
      Africa.
AB  - West Africa has a rich medical history. Herbal medicine has been practiced for
      hundreds of years and the establishment of an effective herbal pharmacopoeia was
      probably the first medical research carried out in West Africa. Arabic medicine
      was practiced in the countries of the Sahel in the 15th and 16th centuries. The
      coming of the Europeans focused research on infectious diseases such as malaria,
      yellow fever and sleeping sickness, to which Europeans were very susceptible and
      which caused devastating epidemics among the populations of their new colonies.
      The end of the colonial era saw the establishment of a few large, well-equipped
      teaching hospitals but these proved too expensive for the newly independent
      states of West Africa to run effectively, and the second generation of West
      African medical schools was based on more modest government hospitals. This led
      to a change in the focus of research away from the more unusual conditions seen
      in a specialist referral hospital to an interest in conditions, such as the
      common infectious diseases, seen more frequently in district hospitals. The
      advent of the primary health care movement in the 1970s was followed by an
      increased emphasis on community studies. Molecular biology is likely to have an
      enormous impact on medicine in general in the coming years. One of the main
      challenges facing medical researchers in West Africa is how these new
      technologies can be used most effectively to improve health in countries with
      limited resources.

PMID- 9593355
TI  - Enhancement of the antimalarial effect of chloroquine by chloropheniramine in
      vivo.
AB  - The efficacy of chloroquine and chloroquine plus chloropheniramine, a histamine
      H1 receptor blocker which reverses chloroquine insensitivity in Plasmodium
      falciparum in vitro, was studied in 96 children with acute symptomatic
      uncomplicated falciparum malaria. The chloroquine/chloropheniramine combination
      produced a significantly higher cure rate than chloroquine alone and cured 77% of
      children with chloroquine treatment failures. Children with chloroquine treatment
      failure had mean plasma chloroquine concentrations above the minimum therapeutic
      concentration for the area. Chloroquine concentrations in plasma and red blood
      cells and ratio of red cell to plasma chloroquine concentrations on days 3 and 7
      after initiation of therapy were not significantly different in the two groups.
      Chloroquine/chloropheniramine produces a higher cure rate than chloroquine alone
      and reverses chloroquine insensitivity in Plasmodium falciparum in vivo. It may
      be a useful way of optimising the antimalarial effect of chloroquine.

PMID- 9593356
TI  - Use of antifilarial IgG4-ELISA to detect Brugia malayi infection in an endemic
      area of Malaysia.
AB  - OBJECTIVE: To evaluate the usefulness of antifilarial IgG4 antibody assay in
      detecting B. malayi infection in a filaria endemic area in Malaysia. METHODS: A
      sandwich ELISA using B. malayi soluble antigen was employed to detect
      antifilarial IgG4 antibodies in serum samples of 330 individuals who comprised 88
      healthy individuals from nonendemic areas, 15 B. malayi microfilaraemic cases, 22
      individuals with soil-transmitted helminthiases, 9 elephantiasis cases and 196
      residents from a B. malayi-endemic area. An O.D. value of > 0.420 at serum
      dilution of 1:400 was used as the cut-off point. This cut-off point was obtained
      by taking the mean optical density (0.252 + 4 S.E.) of 36 negative sera which had
      O.D. values greater than 0.1 at serum dilution of 1:400. RESULTS: All 15
      microfilaraemic persons were positive for antifilarial IgG4 antibody. Non-endemic
      normals, soil-transmitted helminth infected persons and chronic elephantiasis
      cases were negative for antifilarial IgG4 antibody. Of the 196 individuals from
      the filaria endemic area, 37 (18.8%) demonstrated presence of antifilarial IgG4
      antibodies; and only eight individuals (4.1%) were positive for microfilariae.
      All eight microfilaraemic individuals were also positive for antifilarial IgG4
      antibodies. CONCLUSION: Antifilarial IgG4-ELISA could detect 4.6 times more
      positive cases than the microfilaria detection method. With appropriate cut-off
      values that eliminate cross-reactivities, this serological tool is very useful
      for Brugia malayi prevalence surveys and diagnosis.

PMID- 9593357
TI  - Mycobacterium ulcerans infection in a child from Angola: diagnosis by direct
      detection and culture.
AB  - Buruli ulcer, caused by Mycobacterium ulcerans, is a chronic ulcerative skin
      disease, found predominantly in central and west Africa and Australia. A boy of
      2.5 years of age from Angola was admitted to our hospital with severe kwashiokor
      and a large ulcer with undermined edges on the left side of the thorax. Further
      examination revealed anaemia, hypoproteinaemia, bacterial superinfection of the
      ulcer and intestinal parasites. Histological analysis showed acid-fast bacilli
      and histopathological changes typical of Buruli ulcer. M. ulcerans was detected
      by PCR and culture. The patient was treated by surgical excision of diseased
      skin, followed by split-skin grafting. He also received antibiotic therapy
      (ciprofloxacin, clarithromycin, rifabutin, and dapsone). After six months, the
      child was discharged from hospital in good condition. This is the first published
      case of Buruli ulcer from Angola.

PMID- 9593358
TI  - A community randomized controlled trial of insecticide-treated bednets for the
      prevention of malaria and anaemia among primigravid women on the Kenyan coast.
AB  - The effectiveness of insecticide-treated bednets (ITBN) in preventing malaria and
      anaemia among primigravidae living in Kilifi District, Kenya, was assessed by a
      randomized controlled trial between September 1994 and November 1995. All
      residents within 28 community clusters received ITBN in July 1993, whilst
      residents of another 28 clusters served as contemporaneous controls. All resident
      primigravid women with singleton pregnancies attending antenatal care at Kilifi
      District Hospital were eligible for recruitment. 503 primigravidae were
      recruited. 91.4% were anaemic antenatally (Hb < 11 g/dl): 91.0% from the
      intervention arm and 92.0% from the control arm. Severe anaemia (Hb < 7 g/dl) was
      found among 15.1% of intervention women and 20.1% of control women (P = 0.28). No
      significant differences were observed in reports of febrile illness or the
      presence of chloroquine in the serum or peripheral parasitaemia during the third
      trimester between the two groups. In the women delivering in hospital (n = 130),
      there was no association between placental malaria infection and the
      intervention: 77.4% of placentas from control women had evidence of past or
      active infection, compared with 72.0% of placentas from intervention women (P =
      0.76). Similarly, in the women delivering in hospital, ITBN did not improve birth
      weight, and there were no differences in perinatal mortality between the two
      study groups. Despite ITBN having a great impact on paediatric severe malaria and
      mortality in this transmission setting, there was very little impact of ITBN on
      the morbidity associated with malaria infection in primigravidae. Alternative
      strategies are required to tackle this continued public health problem for
      pregnant women living in endemic areas similar to the Kenyan Coast.

PMID- 9593359
TI  - Bacteria and viruses that cause respiratory tract infections during the
      pilgrimage (Haj) season in Makkah, Saudi Arabia.
AB  - OBJECTIVE: To determine the incidence and type of RTI-causing bacteria and
      viruses during a period of epidemic infections. METHOD: A total of 395 sputum
      specimens and 761 throat swabs were collected during the 1991 and 1992 pilgrimage
      seasons (Haj to Makkah Al-Mukarama, Saudi Arabia) from patients referred to one
      hospital and three dispensaries with symptoms of respiratory tract infections.
      All 761 throat swabs of both Haj seasons were also screened for the presence of
      viral pathogens with monoclonal antibodies specific for 7 viruses known to cause
      respiratory infections. RESULTS: Bacterial pathogens were detected in 118 (29.9%)
      specimens. During the 1991 Haj season Haemophilus influenzae was the most
      frequent bacterial pathogen detected (10%), followed by Klebsiella pneumoniae
      (5.2%), Streptococcus pneumoniae (4.8%), Staphylococcus aureus (3.8%) and
      Streptococcus pyogenes (2.4%). In the 1992 Haj season Klebsiella pneumoniae was
      predominant (15.1%), followed by Haemophilus influenzae and Streptococcus
      pneumoniae (12.3%). Screening of all sputum specimens for acid-fast bacteria
      showed that the overall incidence rate of tuberculosis was 1%. Cultures from the
      761 throat swabs were largely negative for bacteria except for Streptococcus
      pyogenes isolated from 7 patients. Viruses were detected in 148 (19.5%) specimens
      with influenza A and adenovirus being the most common viruses. CONCLUSION: The
      pattern of virus prevalence in the 1991 and 1992 pilgrimage seasons was
      identical: influenza A and adenovirus predominated. Thus these two viruses should
      be targeted in future prophylactic measures.

PMID- 9593360
TI  - Schiotz tonometry for glaucoma: are there simple alternatives?
AB  - In the period from October 1991 until August 1992, 864 eye-patients in a rural
      area in south-east Nigeria were examined in order to find simple parameters for
      the screening of glaucoma simplex. Schiotz tonometry was used as the gold
      standard. Investigation of the pupil-reaction with a torch, estimation of the
      pressure of the (closed) eye by digital palpation, and estimations of the
      cup/disc ratio by ophthalmoscopy can be used as an alternative.

PMID- 9593361
TI  - Schistosomiasis haematobia in Mali: prevalence rate in school-age children as
      index of endemicity in the community.
AB  - In a nationwide survey of schistosomiasis conducted in Mali from 1984 to 1989,
      56265 individuals from 323 villages had their urine examined parasitologically
      using a filtration technique. From a sample of 242 children in 3 villages, aged 7
      to 14 years, urine samples were collected and tested for haematuria using reagent
      strips. Analysis of the age-specific prevalence rates of Schistosoma haematobium
      infection showed a strong positive correlation between the prevalence rate in the
      7-14 year-old age group, and both the overall prevalence (r = 0.90; P < 0.001)
      and the prevalences at other ages. An index was derived from this relationship
      using the equation: overall prevalence = -1.14 + 0.74 (prevalence in 7-14 year
      olds). The sensitivity and specificity of reagent strip testing for
      microhaematuria as compared to urine filtration were 73.3% and 83.2%
      respectively. We conclude that reagent strip testing of urine samples collected
      from a sample of individuals aged 7-14 years would be sufficient to estimate the
      overall prevalence of Schistosoma haematobium infection in a Malian community and
      suggest that this assessment procedure be used at the peripheral level of primary
      health care to decide on treatment regimes.

PMID- 9593362
TI  - Relationships between histopathological findings and phylogenetic divergence in
      Trypanosoma cruzi.
AB  - Problems have been raised by natural genetic diversity of Trypanosoma cruzi, the
      causal agent of Chagas' disease, and other protozoa in terms of both basic and
      applied science. T. cruzi manifests a great diversity of medical and biological
      properties which could be the origin of clinical variability in the disease. We
      propose possible correlations between genetic distances, or phylogenetic
      divergence, and histopathological data. To ascertain this aspect, 15 cloned
      stocks pertaining to three major clones or genotypes (19, 20 and 39) were
      compared. Sets of 24 mice infected with each stock were studied for
      histopathological lesions. Brain, heart, lung, liver, spleen, urinary bladder,
      bone marrow, colon, kidney and skeletal muscle were extracted from each mouse.
      Qualitative and quantitative differences showed at histopathological examination.
      An important encephalic softening was found in brains of most mice infected by
      genotype 20, corresponding to areas of inflammation and liquified necrosis. Other
      inflammatory tissue lesions in the histological sections of the three genotypes
      were similar. Skeletal muscle tropism was higher than cardiac tropism in all the
      studied genotypes. All three genotypes shared parasite presence in skeletal
      muscle. Differences related to cardiac tropism were important: in genotype 19,
      50% of studied stocks presented pseudocysts; 20% in genotype 20 and 83% in
      genotype 39. Parasite presence in other tissues was scanty: in brain only in
      genotype 20 and in spleen and liver only in genotype 39. We found important
      histopathogenicity differences among the three studied genotypes, but they do not
      support the hypothesis of zymodeme pathogenic specificity due to the great
      diversity among stocks within each genotype.

PMID- 9593363
TI  - Schistosoma mansoni infection in a recently exposed community in Senegal: lack of
      correlation between liver morphology in ultrasound and connective tissue
      metabolites in serum.
AB  - Four hundred and seventy villagers of Ndombo, a village with recently established
      intensive transmission of Schistosoma mansoni in the Senegal River Basin, were
      enrolled in a study with the intention to assess hepatosplenic morbidity. All
      patients were examined parasitologically and by ultrasound. Hepatic fibrosis
      serum markers were determined in 153 adult patients (aminoterminal propeptide of
      procollagen type III, hyaluronan and laminin). By ultrasound, about 60% of the
      patients showed early stages of hepatic involvement, 3% of the patients
      unequivocally showed severe hepatosplenic pathology (grade 3 according to the
      Managil classification), whereas in another study performed in the same village 3
      years earlier, no patients with severe hepatosplenic pathology had been found. No
      correlation between the aminoterminal propeptide of procollagen type III,
      hyaluronan or laminin and the ultrasound findings could be established. These
      hepatic fibrosis serum markers do not seem to be a sensitive method to detect
      early hepatic fibrosis in schistosomiasis.

PMID- 9593364
TI  - Electron-microscopic examination of Rickettsia tsutsugamushi-infected human
      liver.
AB  - A 33 year-old Thai woman was diagnosed with scrub typhus infection according to
      clinical symptoms, eschar lesions compatible with the disease, and specific
      antibody to Rickettsia tsutsugamushi detected by indirect immunoperoxidase.
      Percutaneous transhepatic needle biopsies were taken before and 7 days after
      treatment with tetracycline to study the pathology of the liver. The liver tissue
      was evaluated by light microscopy, using H & E and Pinkerton's stains, and by
      transmission electron microscopy (TEM). Before treatment it showed reactive
      hepatitis. Rickettsia organisms within the hepatocytes and sinusoids detected by
      Pinkerton's stain appeared as tiny bright-red organisms. By TEM, the rod-shaped
      double-membrane Rickettsiae appeared intact in the cytoplasm of Kupffer's cells
      and hepatocytes. After tetracycline treatment, moderate levels of acidophilic and
      ballooning liver cells were observed. The degree of cytoplasmic organelle damage
      varied, including fatty metamorphosis, depletion of glycogen granules, loss of
      the mitochondrial cristae, dilatation of endoplasmic reticulum and cytoplasmic
      vacuolation. Rickettsia organisms cannot be visualized by Pinkerton's stain but
      were detected by TEM, in markedly vacuolated hepatocytes, in congested sinusoids
      and in Kupffer's cells. Intranuclear Rickettsia were discovered in the
      endothelial nucleus, showing various degrees of injury. Some were mildly
      degenerated, while others exhibited clumping of nucleoprotein at the cytoplasm
      periphery and large vacuolation centrally. Many indented organisms were found,
      and binary fission during Rickettsiae multiplication was always affected.
      Electron-microscopic examination of hepatic injury associated with scrub typhus
      is rare. This is the first ultrastructural localization of Rickettsiae in the
      infected human liver.

PMID- 9593365
TI  - The data presented by Jelinek et al. (1997) should not be taken as evidence
      against an association between resistance to sulphadoxine-pyrimethamine (S/P) and
      mutations in the dihydrofolate reductase gene of Plasmodium falciparum.

PMID- 9593366
TI  - The effect of excimer laser PRK on IOP measurements.

PMID- 9593367
TI  - Intraocular candidiasis in patients with candidemia.

PMID- 9593368
TI  - Laser pointers and color blindness.

PMID- 9593369
TI  - Laser photocoagulation of confluent soft macular drusen.

PMID- 9593370
TI  - Coexisting optic nerve head drusen and glaucoma.

PMID- 9593371
TI  - Complications of macular hole surgery.

PMID- 9593372
TI  - Cosmetic surgery may be hazardous...for the doctor as well as the patient.

PMID- 9593373
TI  - Risk factors for hemiretinal vein occlusion: comparison with risk factors for
      central and branch retinal vein occlusion: the eye disease case-control study.
AB  - OBJECTIVE: Possible risk factors for hemiretinal vein occlusion were identified
      and compared with risk factor profiles for central and branch retinal vein
      occlusion. DESIGN: The design was a multicenter case-control study. METHODS: The
      authors identified 79 patients with hemiretinal vein occlusion (HRVO), 258
      patients with central retinal vein occlusion (CRVO), 270 patients with branch
      retinal vein occlusion (BRVO), and 1142 control subjects at 5 clinical centers.
      Risk factor data were obtained through interviews, clinical examinations, and
      laboratory analyses of blood specimens. RESULTS: Systemic hypertension and
      history of diabetes mellitus were associated with increased risk of HRVO. Risk of
      CRVO increased with history of diabetes, systemic hypertension, and higher
      erythrocyte sedimentation rate (females only); risk of CRVO decreased with
      increasing amounts of physical activity and increasing amounts of alcohol
      consumption. Systemic hypertension, higher body mass index, and higher alpha2
      globulin levels were associated with increased risk of BRVO, whereas higher high
      density lipoprotein levels and increasing levels of alcohol consumption were
      associated with decreased risk of BRVO. Glaucoma history was associated with all
      three types of retinal vein occlusion. CONCLUSION: Patients presenting with
      retinal vein occlusion should be evaluated for cardiovascular disease, diabetes,
      and glaucoma.

PMID- 9593374
TI  - Retinal blood flow in nonischemic central retinal vein occlusion.
AB  - OBJECTIVE: The authors studied the changes in retinal blood flow (RBF) and oxygen
      reactivity in a major temporal vein in patients with central retinal vein
      occlusion (CRVO). PARTICIPANTS: Eleven patients with nonischemic CRVO
      approximately 7 weeks from onset of disease. INTERVENTION: Laser Doppler
      velocimetric measurement of RBF and vessel reactivity to inhaling 60% oxygen.
      Measurements were performed at baseline and 3 months. RESULTS: Flow velocity in
      the affected eye had increased significantly by 3 months, from 1.6 +/- 0.4
      cm/second to 2.0 +/- 0.4 cm/second (P = 0.02). Retinal blood flow, however,
      remained unchanged (13.7 +/- 5.8 microl/minute versus 15.0 +/- 6.5
      microl/minute). The two comparable RBF values, despite differing velocity values,
      suggest that the relatively normal baseline value was achieved through higher
      intravascular pressure at baseline (Bernoulli's principle). This is supported by
      the fact that oxygen reactivity had improved from 2.1% +/- 3.6% at baseline to
      3.8% +/- 3.1% (P = 0.001) at 3 months, which suggests an improved ability to
      respond to hyperoxia from reduced intravascular pressure. CONCLUSION:
      Intravascular pressure in CRVO appears to continue to decrease during the first 5
      months after the onset of CRVO, indicating continuing reduction in the degree of
      outflow obstruction during this time.

PMID- 9593375
TI  - The risk of missing angle neovascularization by omitting screening gonioscopy in
      acute central retinal vein occlusion.
AB  - OBJECTIVE: The purpose of the study was to determine whether angle
      neovascularization can occur without pupillary margin neovascularization in
      central retinal vein occlusion (CRVO). DESIGN: The study design was a prospective
      study of the main question and a retrospective study of ancillary issues.
      PARTICIPANTS: The authors examined 105 eyes of 100 patients with CRVO having
      clinical evidence of ischemia between July 1, 1986, and March 18, 1996.
      INTERVENTION: The authors looked for iris and angle neovascularization with both
      undilated slit-lamp biomicroscopy and Zeiss four-mirror gonioscopy. MAIN OUTCOME
      MEASURES: The presence of anterior segment neovascularization was measured.
      RESULTS: Of 34 eyes developing anterior segment neovascularization, 4 (12%)
      developed angle neovascularization without pupillary margin neovascularization
      over a mean follow-up of 2.2 +/- 2.4 standard deviation years. CONCLUSIONS: Angle
      neovascularization can occur without pupillary margin involvement in CRVO,
      implying the necessity of screening gonioscopy and supporting the Central Vein
      Occlusion Study conclusion (based on a photographic technique not used
      clinically).

PMID- 9593376
TI  - Proliferative vitreoretinopathy: a natural history of the fellow eye.
AB  - OBJECTIVE: To determine how often the fellow eyes of patients with proliferative
      vitreoretinopathy (PVR) harbor a vision-threatening condition at presentation; to
      determine how often the fellow eyes of patients with PVR develop vision
      threatening conditions; and to determine how often the fellow eyes of patients
      with PVR lose vision. DESIGN: A retrospective case review design was used.
      PARTICIPANTS: Two hundred and forty-nine patients with PVR were studied.
      INTERVENTION: The authors observed the fellow eye of eyes with PVR for vision
      threatening pathology. MAIN OUTCOME MEASURES: The primary anatomic endpoint of
      this study was the detection of vision-threatening pathology in the fellow eye of
      patients with PVR. Secondary outcome measures included the development of visual
      loss in the fellow eye. RESULTS: A wide variety of vision-threatening conditions
      were diagnosed in the fellow eyes of patients with PVR. Of patients meeting entry
      criteria with reliable follow-up data, greater than 50% of fellow eyes
      demonstrated vision-threatening pathology at some point during follow-up.
      CONCLUSIONS: Patients who develop PVR in one eye are at considerable risk for
      developing vision-threatening pathology or vision-damaging conditions in the
      fellow eye. This information should be carefully considered when making surgical
      decisions in patients facing PVR surgery.

PMID- 9593377
TI  - Alcohol consumption and the 5-year incidence of age-related maculopathy: the
      Beaver Dam eye study.
AB  - OBJECTIVE: This study evaluated alcohol consumption as a risk factor for
      incidence of age-related maculopathy (ARM). DESIGN: Persons aged 43 to 86 years
      in 1988 in Beaver Dam, Wisconsin, were examined from 1988 through 1990 and 1993
      through 1995, n = 3684. The presence and severity of ARM at both examinations
      were determined from gradings of stereoscopic fundus photographs using the
      Wisconsin Age-related Maculopathy Classification System. Alcohol consumption was
      determined by self-report. RESULTS: Men drinking at least 78 g/week of alcohol
      from beer had a higher 5-year age-adjusted incidence of early ARM (10.6%) than
      did men who did not drink beer (6.9%), but the test for trend was only borderline
      significant (P = 0.08). However, incidence of soft indistinct drusen (P = 0.01),
      increased drusen area (P < 0.01), and confluent drusen (P = 0.02) are all
      associated with beer drinking in men. Increased retinal pigment and retinal
      pigment epithelial depigmentation are not associated with beer drinking in men or
      women nor are any lesions associated with total alcohol consumption or
      consumption from liquor or wine in either men or women. CONCLUSIONS: Except for
      an association of beer drinking with retinal drusen in men, consumption of
      alcoholic beverages is not likely to be an important risk factor for incidence of
      ARM.

PMID- 9593378
TI  - Vitreoretinal surgery outcomes: results of a patient satisfaction/functional
      status survey.
AB  - OBJECTIVE: This study aimed to assess patient satisfaction and change in
      functional status after surgery for epiretinal membrane (ERM), rhegmatogenous
      retinal detachment (RRD), and complex retinal detachment (CRD). This study also
      aimed to determine whether objective measures of vision are predictive of
      subjective improvement after surgery. DESIGN: The study design included patient
      interviews and retrospective chart review. PARTICIPANTS: Participants were those
      patients who underwent surgery for ERM, RRD, or CRD by one surgeon at the Bascom
      Palmer Eye Institute between January 1, 1993, and December 31, 1994.
      INTERVENTION: Patient satisfaction and patients' perceptions of the impact of
      surgery on their functional status were assessed by telephone interviews
      conducted by one interviewer at least 6 months after surgery. MAIN OUTCOME
      MEASURES: Responses to patient satisfaction survey and subjective change in
      patients' functional status were measured. RESULTS: Of 187 eligible patients, 146
      (78.1%) could be contacted and all agreed to participate. Ninety patients (61.6%)
      reported improved functioning after surgery in 2 or more of the 5 activities
      investigated. Twenty-one patients (14.4%) reported worse postoperative vision
      than expected, but only 5 patients (3.4%) thought surgery had not been
      worthwhile. One hundred forty-three patients (97.9%) reported adequate
      explanation of surgery and its expected results. Patients with preoperative study
      eye visual acuity between 20/40 and 20/200 were most likely to improve in two or
      more activities. Lower preoperative worse eye vision and better final study eye
      vision were associated with a greater likelihood of satisfaction after surgery.
      Diagnostic category was not predictive of change in functional status or patient
      satisfaction. CONCLUSIONS: There is a high rate of patient satisfaction and
      improved functional status after surgery for ERM, RRD, and CRD, even among
      patients with good fellow eye vision.

PMID- 9593379
TI  - Surgical management of retinal detachments related to coloboma of the choroid.
AB  - OBJECTIVE: This study aimed to develop a rationale for the management of retinal
      detachments related to choroidal coloboma and to study the outcome of their
      management. DESIGN: The study design was a retrospective study. PARTICIPANTS: A
      total of 85 eyes of 81 patients with retinal detachments related to coloboma of
      the choroid participated. INTERVENTION: All eyes underwent pars plana vitrectomy
      with internal tamponade using silicone oil (80 eyes) or perfluropropane gas (5
      eyes). Behavior of the retina on fluid-air exchange was used to guide the further
      steps of surgery. Endolaser was performed along the coloboma border. Silicone oil
      was removed in 80% of eyes. The main outcome measures were retinal reattachment
      and visual recovery. RESULTS: Recurrent retinal detachment occurred in 16.3% of
      silicone oil-filled eyes and 60% of gas-filled eyes. After silicone oil removal,
      15.6% of eyes had recurrent retinal detachment. After a mean follow-up of 13.4
      months, 81.2% of eyes had attached retina and 69.4% recovered equal to or better
      than 10/200 visual acuity. CONCLUSION: Retinal detachment secondary to coloboma
      of choroid is treated best by pars plana vitrectomy along with silicone oil
      tamponade. Gas tamponade has limited indications. Clinical evaluation of the
      extent of retinal detachment within the colobomatous area and the behavior of the
      retina on fluid-air exchange help the authors understand the pathogenesis of the
      retinal detachment and plan a rational therapy.

PMID- 9593381
TI  - Treatment and histopathology of a congenital vitreous cyst.
AB  - OBJECTIVE: This study aimed to evaluate the treatment efficacy of a congenital
      vitreous cyst and to examine the cyst histopathologically to determine its
      cellular makeup and possible origin. STUDY DESIGN: The study design was a case
      report, including a clinicopathologic correlation. INTERVENTION: A 35-year-old
      woman with a known vitreous cyst since childhood became increasingly troubled by
      its symptoms. The cyst was treated initially with argon laser photocoagulation.
      Vitrectomy subsequently was performed because the deflated cyst remained near the
      visual axis. Histopathologic studies included light and electron microscopy;
      immunocytochemistry for actin and glial fibrillary acidic protein (GFAP); and
      enzyme histochemistry for carbonic anhydrase (CA). RESULTS: The cyst was composed
      of a single layer of heavily pigmented cells with a thick basement membrane along
      the internal borders of the cells. Ultrastructurally, the cells were connected
      with tight junctions, had microvillous processes at their apices, and contained
      numerous large melanosomes in various stages of maturity, including
      premelanosomes. Immunochemistry showed the cells were positive for actin but
      negative for GFAP. Enzyme histochemical staining for CA also was strongly
      positive. CONCLUSIONS: The confinement of this cyst to the region of Cloquet's
      canal, the presence of a Mittendorf's dot, the cyst's existence for many years,
      and the finding of pigment epithelial-type cells having immature melanosomes (a
      feature not seen after birth in normal pigment epithelium) lead the authors to
      believe that this cyst was a congenital remnant of the primary hyaloidal system.
      Because pigmented cells are not normally present in this part of the eye, the
      cyst was a choristoma of the primary hyaloidal system.

PMID- 9593380
TI  - Ophthalmologic findings in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
      caused by the G1528C mutation: a new type of hereditary metabolic
      chorioretinopathy.
AB  - OBJECTIVE: The purpose of the study was to determine the nature and course of
      ophthalmic abnormalities in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)
      deficiency, a recently discovered disorder of mitochondrial fatty acid beta
      oxidation. STUDY DESIGN: The study design was a cohort (case series).
      PARTICIPANTS: A retrospective review of the records of 15 children who had died
      during their first 2 years was performed. Also performed were a longitudinal
      reanalysis and cross-sectional clinical examination of four long-term survivors
      aged 5 to 31 years. MAIN OUTCOME MEASURES: Visual acuity, refraction, visual
      fields, ophthalmoscopy, fluorescein angiography, biometry, corneal topography,
      electroretinography (ERG), visual-evoked potentials (VEPs), color vision, and
      dark adaptation were measured. RESULTS: In seven children, ophthalmoscopic
      findings were within normal limits at 3 days to 13 months of age (median, 4.8
      months). In 11 children, a granular retinal pigment epithelium (RPE), with or
      without pigment clumping in the macula, was seen at 4 months to 5 years of age
      (median, 9 months). Two long-term survivors, 16 and 31 years of age, eventually
      had circumscribed atrophy of the choroid, RPE, and retina, which coincided with a
      posterior staphyloma type 1. They had progressive axial myopia starting at 6 and
      12 years of age and later paracentral scotomas leading to poor central vision.
      They suffered from early difficulty with mesopic vision, glare, and a severe
      generalized color vision deficiency that started as a tritanomaly. A third
      survivor was mildly myopic at 5 years of age. All four surviving patients had
      visually insignificant, flake-like supranuclear opacities in the lens. The ERG
      initially was normal but deteriorated during the first decade and later was
      unrecordable. The VEP responses remained fairly normal. Initially, angiography
      showed no blockade of the choroidal fluorescence because of the thin RPE. Filling
      of choroidal vessels was delayed, and the choriocapillaris and, later, larger
      choroidal vessels in the posterior pole became nonperfused. CONCLUSIONS: In LCHAD
      deficiency, the fundus is normal at birth (stage 1). Soon, however, pigment
      dispersion occurs in the RPE (stage 2), followed by circumscribed chorioretinal
      atrophy, occlusion of choroidal vessels, and deterioration of central vision,
      often with relative sparing of the peripheral fundus (stage 3). Finally,
      posterior staphylomas and central scotomas may develop (stage 4). Developmental
      cataract, progressive myopia, and deterioration of visual fields and color vision
      are new findings in LCHAD deficiency. The chorioretinopathy and abnormal ERG
      precede the development of myopia and posterior staphyloma, which, in turn,
      coincide with the loss of macular vision. The authors postulate that the RPE or
      choriocapillaris is primarily affected. Awareness of the characteristic ocular
      features is important because of an opportunity for dietary treatment, genetic
      counseling, and prenatal diagnosis.

PMID- 9593382
TI  - Antioxidant vitamins and nuclear opacities: the longitudinal study of cataract.
AB  - OBJECTIVE: The association of antioxidant nutrients and risk of nuclear
      opacification was evaluated in the Longitudinal Study of Cataract. DESIGN:
      Nutritional data were collected at baseline on the 764 participants, which
      included assessment of dietary intake, use of vitamin supplements, and plasma
      levels of vitamin E. Ophthalmologic and other data were collected at baseline and
      at yearly follow-up visits, including lens photographs, which were graded using
      the Lens Opacities Classification System III protocol. MAIN OUTCOME MEASURES:
      Analyses examined whether the nutritional factors at baseline were related to
      increases in nuclear opacification at follow-up. The MULCOX2 approach, an
      extension of the Cox regression model, was used. Results are presented as
      relative risks (RRs) and 95% confidence intervals. INTERVENTION: Intervention was
      not applicable. RESULTS: The risk of nuclear opacification at follow-up was
      decreased in regular users of multivitamin supplements (RR = 0.69; 0.48-0.99),
      vitamin E supplements (RR = 0.43; 0.19-0.99), and in persons with higher plasma
      levels of vitamin E (RR = 0.58; 0.36-0.94). CONCLUSIONS: In regular users of
      multivitamin supplements, the risk of nuclear opacification was reduced by one
      third; in regular users of vitamin E supplements and persons with higher plasma
      levels of vitamin E, the risk was reduced by approximately half. These results
      are similar to those obtained in our earlier case-control study. Because these
      data are based on observational studies only, the results are suggestive but
      inconclusive. The possible effect of nutritional supplements on the lens requires
      confirmation by ongoing clinical trials.

PMID- 9593383
TI  - Fixation elements on plate intraocular lens: large positioning holes to improve
      security of capsular fixation.
AB  - OBJECTIVE: This study aimed to evaluate in rabbit eyes the effects of large
      positioning holes in one-piece silicone plate-haptic intraocular lenses (IOLs)
      with respect to security of capsular bag fixation. Mechanical strength of
      capsular fixation is correlated with the histologic findings of regenerating lens
      material and fibrous tissue ingrowth through the positioning holes on silicone
      plate IOLs, comparing capsules implanted with large-hole style plate IOLs to
      fellow capsules implanted with small-hole style plate IOLs. DESIGN: The study
      design was a prospective, randomized, experimental study. PARTICIPANTS: A total
      of 40 fellow capsular bags from 20 New Zealand white rabbits were examined.
      Capsules implanted with conventional small-hole silicone plate IOLs were used as
      the control in all pairs of fellow capsules. INTERVENTION: Phacoemulsification
      and implantation of a silicone plate IOL with small positioning holes in one eye
      and implantation of a silicone plate IOL with large positioning holes in the
      fellow eye were measured. All rabbits were killed at 2 months. The force required
      to extract the IOLs from the capsular bag was measured. All capsular bags
      underwent histopathologic analysis. MAIN OUTCOME MEASURES: Extraction force
      measurements and histopathologic examination, comparing capsules implanted with
      small-hole plate IOLs with fellow capsules implanted with large-hole plate IOLs,
      were measured. RESULTS: The large-hole style IOL required significantly more
      force to extract from the capsular bag compared to the conventional small-hole
      style (P = 0.003). Histologically, proliferating lens epithelial material and
      fibrous tissue were observed growing through all of the large positioning holes
      (synechia formation) but not through any of the small positioning holes.
      CONCLUSIONS: Silicone plate IOLs with large positioning holes become affixed more
      firmly within the capsular bag compared to conventional small-hole plate IOLs.
      These findings suggest that large holes in silicone plate IOLs allow for superior
      capsular bag fixation. This should reduce the rates of decentration and
      dislocation.

PMID- 9593384
TI  - Heparin surface-modified intraocular lenses in patients with inactive uveitis or
      diabetes.
AB  - OBJECTIVE: This study aimed to determine whether heparin surface-modified (HSM)
      intraocular lenses (IOLs) with a hydrophilic surface would reduce cell adherence
      and other postoperative changes compared with the conventional
      polymethylmethacrylate (PMMA) IOLs in patients with either diabetes mellitus or
      inactive uveitis. DESIGN: The study design was a randomized, double-masked,
      clinical trial. PARTICIPANTS: Twenty-five patients with bilateral cataracts, 14
      with inactive anterior uveitis and 11 with diabetes, with an age range of 11 to
      81 years (mean, 52.8 years) participated. INTERVENTION: Bilateral cataract
      extraction with posterior chamber IOL implantation was measured, each patient
      receiving an HSM lens in one eye and a PMMA lens in the other. Pharmacia one
      piece HSM and PMMA IOLs were used. Postoperative ocular changes were evaluated at
      regular intervals for 24 months in patients with inactive uveitis and for 6
      months in patients with diabetes. Patients and physicians alike were unaware of
      which eye contained which lens until postoperative results were compiled. Records
      were kept by a study coordinator. MAIN OUTCOME MEASURES: Comparisons of posterior
      synechiae, IOL cellular deposits, and posterior capsular fibrosis between PMMA
      and HSM IOLs were measured. RESULTS: Using the chi-square test, no statistically
      significant difference was found between the HSM and PMMA IOLs in the number of
      cellular deposits found on the anterior IOL surface, the number of adhesions
      between the iris and IOL, or the incidence of capsular opacification. CONCLUSION:
      The HSM and PMMA IOLs showed similar postoperative results in patients with
      inactive uveitis or diabetes mellitus.

PMID- 9593385
TI  - Congenital esotropia in Olmsted County, Minnesota.
AB  - OBJECTIVE: To determine the birth prevalence of and risk factors associated with
      congenital esotropia. DESIGN: Population-based prevalence study with nested case
      control study. PARTICIPANTS: All residents of Olmsted County, Minnesota who were
      diagnosed with congenital esotropia and born between January 1, 1980 and December
      31, 1989 (n = 47). Control subjects were chosen by selecting the next two
      sequential births to parents residing in Olmsted County, Minnesota (n = 94).
      METHODS: Cases were identified through the Medical Diagnostic Index of Mayo and
      the Rochester Epidemiology Project. The community medical records were reviewed
      to confirm case status and ascertain risk factor information. MAIN OUTCOME
      MEASURE: Birth prevalence of congenital esotropia. RESULTS: Forty-seven cases
      were identified from 17,536 live births, for a birth prevalence of 27 per 10,000
      (95% confidence interval [CI], 20-35). Congenital esotropia was associated with
      prematurity (odds ratio [OR], 11.5; 95% CI, 3.4-39.2), a birth weight less than
      2500 grams (OR, 4.6; 95% CI, 1.7-12.9), a low Apgar score at 1 minute (OR, 4.3;
      95% CI, 1.7-11.2) and at 5 minutes (OR, 6.3; 95% CI, 1.3-30.7), and a family
      history of strabismus (OR, 3.5; 95% CI, 1.5-8.3). CONCLUSIONS: The birth
      prevalence of congenital esotropia in Olmsted County, Minnesota is lower than
      previous estimates. Prematurity, low birth weight, low Apgar scores, and a family
      history of strabismus are significant risk factors for congenital esotropia.

PMID- 9593386
TI  - Traumatic hyphema: outcomes of outpatient management.
AB  - OBJECTIVE: This study aimed to compare the outcomes of outpatient and inpatient
      management of layered hyphema. DESIGN: The charts of all patients with traumatic
      layered hyphema treated in the Massachusetts Eye and Ear Infirmary Emergency Ward
      between January 1991 and November 1995 were analyzed retrospectively. Patients
      with a diagnosis of microscopic hyphema, ruptured globe, or posterior segment
      injury other than commotio retinae on their initial emergency department visit
      were excluded. The study patients were compared with an historic control group of
      patients with hyphema who had been treated at the same institution from July 1986
      to February 1989. PARTICIPANTS: A total of 154 patients met the study criteria.
      These were compared with 119 patients in the historic control group.
      INTERVENTION: Of the study patients, 5% were admitted on the day of presentation,
      95% were treated initially as outpatients, and 4% subsequently were admitted. All
      of the patients in the historic control group were treated with initial hospital
      admission. MAIN OUTCOME MEASURES: The rebleed rates of the study and control
      groups were compared. The final recorded visual acuity and causes of best
      corrected visual acuity worse than 20/30 were analyzed for the study group.
      RESULTS: The rebleed rates of the study group and the historic control group were
      4.5% and 5.0%, respectively (P > 0.05). The rebleed rates of the study patients
      initially treated as outpatients and the historic control group were 3.4% and 5%,
      respectively (P > 0.05). The rebleed rates of study patients who did not receive
      aminocaproic acid and the subset of historic control patients who received
      aminocaproic acid were 3.3% and 4.8%, respectively (P > 0.05). Ninety-six percent
      of study patients achieved a final best-corrected visual acuity of 20/30 or
      better. Causes of a final documented visual acuity worse than 20/30 included loss
      of patient follow-up before resolution of the hyphema, traumatic cataract,
      macular hole, and macular degeneration. CONCLUSIONS: In the authors'
      predominantly white patient population, close outpatient follow-up of traumatic
      hyphemas appears to be safe and effective. Hospitalization for hyphema does not
      appear to decrease the rate of rebleeding. Decreased vision in the setting of
      traumatic hyphema generally results from comorbidities not affected by inpatient
      management.

PMID- 9593388
TI  - The effect of ocular dominance on the performance of professional baseball
      players.
AB  - OBJECTIVE: The purpose of the study was to determine whether a performance
      difference exists between baseball players with "same" (right-right) and
      "crossed" (right-left) hand-ocular dominance. DESIGN: A cohort study design was
      used. PARTICIPANTS: Four hundred and ten major and minor league members of the
      Los Angeles Dodgers professional baseball team. INTERVENTION: Measurement of
      ocular dominance. MAIN OUTCOME MEASURES: Batting average and earned run average
      (ERA). RESULTS: Same/crossed dominance (with P values in parentheses) are as
      follows: Batting averages: major league-0.271/0.251 (0.20); minor league
      0.274/0.270 (0.57); ERA: major league-3.34/3.56 (0.66); minor league-4.00/4.20
      (0.54). CONCLUSIONS: Hand-ocular dominance patterns do not have an effect on
      batting average or ERA.

PMID- 9593387
TI  - Screening for amblyopia in preverbal children with photoscreening photographs.
      National Children's Eye Care Foundation Vision Screening Study Group.
AB  - OBJECTIVE: This study aimed to determine the ability of healthcare professionals
      and lay volunteers to grade photoscreening photographs. DESIGN: The study design
      was a cross-sectional study. PARTICIPANTS AND INTERVENTION: One hundred children
      3 years of age or younger received a complete ophthalmologic examination and were
      photographed using the Medical Technology Innovations (MTI) photoscreener. Twenty
      six children had normal examination results, and the remaining 74 children had
      conditions that are of interest for pediatric screening, including strabismus,
      refractive error, media opacities, and ptosis. Eighteen volunteers, including
      pediatric ophthalmologists, pediatricians, ophthalmic technicians, health
      department nurses, Prevention of Blindness Society personnel, and Lions Club
      volunteers, graded each of the 100 photoscreening photographs. MAIN OUTCOME
      MEASURES: Sensitivity and specificity of vision screening and of photograph
      grading were measured. RESULTS: Results from various graders yielded
      sensitivities ranging from 37% to 88% and specificities ranging from 40% to 88%.
      No single grader achieved sensitivity and specificity both greater than 70%. The
      grading of the manufacturer's representative had a sensitivity of 43% and a
      specificity of 85%. Sensitivity decreased to 31% for strabismus and 18% for
      refractive error when the correct type of strabismus or refractive error was
      required to be considered true-positives. Results were not positively correlated
      with the ophthalmologic knowledge of the participant. CONCLUSIONS: The wide
      variability in sensitivities and specificities among graders indicates
      inconsistent photograph interpretation skills or deficient screening guidelines
      or both. For off-axis photoscreening as implemented by the MTI system to become a
      useful vision-screening method, additional photograph interpretation skill
      transfer may be beneficial, although not necessarily sufficient.

PMID- 9593389
TI  - Argyll Robertson: 'twas better to be his pupil than to have his pupil.
AB  - The Scottish ophthalmologist Douglas Argyll Robertson (1837-1909) is best known
      for his description of the syphilitic pupil. He also made important contributions
      concerning the ocular effects of physostigmine and to filtration surgery for
      glaucoma. Outside of his medical practice, he was club champion at the Royal and
      Ancient Golf Club, St. Andrews, and the Honorable Company of Edinburgh Golfers
      many times. He was a champion archer of the Royal Company of Archers, the Queen's
      Bodyguard in Scotland. Robertson was honored as surgeon-oculist in Scotland to
      Queen Victoria and to King Edward VII.

PMID- 9593390
TI  - A comparison of the Marcus Gunn and alternating light tests for afferent
      pupillary defects.
AB  - OBJECTIVE: The authors compared two methods, the Marcus Gunn test and the
      alternating light test, for detecting a relative afferent pupillary defect.
      DESIGN: A randomized, prospective clinical trial. PARTICIPANTS: Fourteen patients
      with unilateral optic neuropathy. INTERVENTION: The Marcus Gunn and alternating
      light tests were performed on each patient. MAIN OUTCOME MEASURES: The results of
      the Marcus Gunn and altemating light tests for detecting a relative afferent
      pupillary defect on the affected side. RESULTS: The Marcus Gunn test was able to
      identify the affected eye in only 8 of 14 patients, whereas the alternating light
      test correctly identified the affected eye in 13 of 14 patients. Results of the
      Marcus Gunn test were indeterminate in 4 of 14 patients and were incorrect in 2
      of 14 patients. Results of the alternating light test were indeterminate in one
      patient and never incorrectly identified the affected eye. CONCLUSION: The
      alternating light test is superior to the Marcus Gunn test for detecting relative
      afferent pupillary defects.

PMID- 9593391
TI  - Optic neuropathy associated with sleep apnea syndrome.
AB  - OBJECTIVE: The study aimed to determine ocular abnormalities in sleep apnea
      syndrome (SAS), an entity characterized by repetitive upper airway obstructions
      during sleep, inducing hypoxia and sleep disruption with the risk of
      cardiovascular and neurologic sequelae. DESIGN: The study design was a case
      series. PARTICIPANTS: Nine patients referred for evaluation of suspected SAS
      participated. INTERVENTION: Complete ophthalmologic examination, including
      computerized perimetry, was performed. MAIN OUTCOME MEASURES: Correlations
      between the respiratory disturbance index (RDI) during night sleep, a value used
      to diagnose and to grade SAS, and visual field indices using the Spearman rank
      correlation coefficient (r(s)) were measured. RESULTS: One patient was excluded
      from the statistical analysis because of optic nerve drusen with constricted
      visual fields, another because of tilted discs with corresponding temporal visual
      field defects. All three patients with severe SAS and one patient with moderate
      SAS had relative nasal arcuate visual field defects; two patients with severe SAS
      also had paracentral relative defects. One patient with normal polysomnographic
      result and two patients with mild or moderate SAS had normal visual fields. The
      RDI correlated positively with the mean visual field defect (r(s) = 0.81, P <
      0.05) and with the visual field loss variance (r(s) = 0.78, P < 0.05). The
      clinical ophthalmologic examination results were normal in all seven patients. In
      two of the three patients with severe SAS treated with continuous positive airway
      pressure (CPAP), visual field defects remained stable over 18 months. The patient
      with optic nerve drusen also had severe SAS and was, therefore, treated with
      CPAP. His constricted visual fields improved dramatically after treatment.
      CONCLUSIONS: Visual fields of patients with SAS showed defects consistent with an
      optic neuropathy. The CPAP therapy seems to stabilize or even reverse visual
      field defects.

PMID- 9593393
TI  - Bimanual trabecular aspiration in pseudoexfoliation glaucoma: an alternative in
      nonfiltering glaucoma surgery.
AB  - OBJECTIVE: The primary cause of intraocular pressure (IOP) elevation in
      pseudoexfoliation glaucoma is obstruction of the intertrabecular spaces by
      exfoliation material. Previously, the authors reported on a new concept of
      nonfiltering glaucoma surgery-trabecular aspiration-designed to increase
      trabecular outflow in pseudoexfoliation glaucoma. In the current study, a
      description of the modified instrument, its refined surgical technique, and long
      term clinical results will be given to substantiate the efficacy of trabecular
      aspiration in the surgical management of pseudoexfoliation glaucoma. STUDY
      DESIGN: The study design was a prospective and nonrandomized study. PARTICIPANTS:
      A total of 68 eyes of 54 patients suffering from medically uncontrolled
      pseudoexfoliation glaucoma were treated by bimanual trabecular aspiration. Thirty
      four eyes of 28 pseudoexfoliative patients treated by standard trabeculectomy
      constituted the control group. INTERVENTION: Trabecular debris and pigment were
      cleared with a suction force of 100 to 200 mmHg under light tissue-instrument
      contact using a modified intraocular aspiration probe. The aspiration cannula is
      400 microm in diameter and horizontally angulated at 45 degrees. Irrigation of
      the anterior chamber was performed via a separate irrigation cannula. MAIN
      OUTCOME MEASURES: The IOP and number of medications before and after surgery were
      measured. RESULTS: In 42 eyes of 36 patients, trabecular aspiration was performed
      in combination with cataract extraction and lens implantation. The IOP dropped
      from 32.4 +/- 7.2 mmHg (range, 23-52 mmHg) under maximal tolerated medical
      therapy before surgery to 18.7 +/- 1.7 mmHg (range, 16-23 mmHg) at 2 years after
      surgery, with 54% of patients being controlled without medication. In 22 eyes of
      19 patients, trabecular aspiration was performed as primary surgical
      intervention. The IOP dropped from 31.3 +/- 7.1 mmHg (range, 23-42 mmHg) before
      surgery to 16.8 +/- 3.4 mmHg (range, 12-23 mmHg) at 18 months after surgery, with
      45% of patients not taking medication. CONCLUSIONS: Bimanual trabecular
      aspiration is safe and efficacious in decreasing IOP both with and without
      cataract extraction in pseudoexfoliation glaucoma. However, there seems to be a
      slight regression in effect over time attributed to undisturbed liberation of
      exfoliative debris. Argon-laser trabeculoplasty before trabecular aspiration
      reduces the IOP-lowering effect of this procedure. A prospective, randomized,
      multicenter study is warranted to finally assess the potential of trabecular
      aspiration in pseudoexfoliation glaucoma.

PMID- 9593392
TI  - Effect of optic nerve head drusen on nerve fiber layer thickness.
AB  - OBJECTIVE: The purpose of the study was to evaluate the effect of optic nerve
      head drusen (ONHD) on nerve fiber layer (NFL) thickness by visual field testing,
      red-free photography of NFL, and optical coherence tomography (OCT). DESIGN: The
      study design was a prospective clinical study. PARTICIPANTS: Twenty-three eyes of
      15 consecutive patients with ONHD and 27 eyes of 27 age-matched control subjects
      participated. INTERVENTION: Ophthalmologic examination, color and red-free
      photography, automated Humphrey visual field testing, and OCT were performed.
      Each of the drusen study eyes were graded on a scale of 0 to III based on the
      amount of visible ONHD. Grade 0 represented the absence of clinically visible
      ONHD, and grade III represented an optic nerve head with abundant drusen. MAIN
      OUTCOME MEASURES: Findings from clinical evaluation and color optic nerve head
      photographs and NFL evaluation by red-free photography, visual fields, and OCT
      were measured. RESULTS: The number of study eyes with visual field defects
      increased with the higher grade drusen discs, corresponding both with
      progressively thinner NFL measurements by OCT and NFL loss shown by NFL
      photography. The NFL evaluation showed NFL thinning by red-free photography in 12
      (71%) of 17 eyes with visible drusen (grades I-III discs) and visual field
      defects in 9 (53%) of 17 eyes in this group. By OCT measurements, the superior
      and inferior NFLs were significantly thinner in the eyes with visible ONHD
      compared with those of control eyes in the superior quadrant (P < 0.001) and
      inferior quadrant (P = 0.004). Compared with grade 0 discs, grades I through III
      discs showed statistically significant thinning of the NFL superiorly (P <
      0.001). No statistical significant thinning of the NFL was seen in grade 0 discs
      compared with those of control subjects. CONCLUSIONS: Optical coherence
      tomography is able to detect NFL thinning in eyes with ONHD and appears to be a
      sensitive and early indicator of NFL thinning. Increased numbers of clinically
      visible ONHD correlated with NFL thinning shown by OCT measurements and both
      visual field defects and NFL loss seen by red-free photography.

PMID- 9593394
TI  - Ocular opportunistic infection incidences among patients who are HIV positive
      compared to patients who are HIV negative.
AB  - OBJECTIVE: The purpose of the study was to examine the incidence of ocular
      opportunistic infections among patients who are human immunodeficiency virus
      (HIV) positive compared to patients who are HIV negative. DESIGN: The study
      design was a retrospective cohort study. PARTICIPANTS: All patients were
      recruited from 1984 until 1995 at the San Francisco General Hospital.
      INTERVENTION: Incidences for numerous diagnoses were compared among the exposure
      group (HIV positive) and nonexposed control group (HIV negative). MAIN OUTCOME
      MEASURES: The diagnoses studied were cytomegalovirus (CMV) retinitis, herpes
      zoster ophthalmicus, Pneumocystis carinii choroidopathy, herpes simplex
      keratitis, Toxoplasma retinitis, fungal retinitis, ocular syphilis, and ocular
      lymphoma. RESULTS: Among the HIV-positive pool, there were 1800 patient visits
      with a total of 5200 person-years of follow-up. Among the HIV-negative control
      pool, there were 48,200 patient visits with a total of 30,100 person-years of
      follow-up. Incidence rates were calculated using the product-limit method, and
      risk ratios were calculated using the Cox proportional hazards model. Incidence
      rate differences were calculated using the incidence density method. Among the
      outcomes studied, only CMV retinitis, herpes zoster ophthalmicus, and, to a
      lesser extent, Toxoplasma retinitis showed both an elevated risk ratio and rate
      difference among patients who were HIV positive compared to patients who were HIV
      negative. Of the other outcomes studied, either the risk ratio, rate difference,
      or both were similar among patients who were HIV positive compared to patients
      who were HIV negative. CONCLUSIONS: Not all ocular infections seen in patients
      who are HIV positive should be considered opportunistic, because many occur with
      similar incidence among patients who are HIV negative. The biologic reasons for
      this will require further study.

PMID- 9593395
TI  - Intraoperative mitomycin C to prevent recurrence of pterygium after excision: a
      30-month follow-up study.
AB  - OBJECTIVE: The purpose of the study was to examine the efficacy of intraoperative
      mitomycin C (MMC) in preventing recurrence of pterygium after excision and the
      postoperative complications encountered. DESIGN: The study design was a
      prospective, randomized, clinical trial. PARTICIPANTS: A total of 180 primary and
      recurrent pterygia were recruited for the study. They were randomized into five
      groups: A, control with no MMC; B, 0.02% MMC for 5 minutes; C, 0.04% MMC for 5
      minutes; D, 0.02% MMC for 3 minutes; and E, 0.04% MMC for 3 minutes.
      INTERVENTION: All patients received pterygium excision with or without the above
      four modes of intraoperative MMC application. MAIN OUTCOME MEASURES: Recurrence
      of pterygium and postoperative complications such as superficial scleral melting
      were measured. RESULTS: At a mean follow-up of 30 (groups A-C) and 20 months
      (groups D and E), the respective recurrence rates in groups A through E were 75%,
      8.3%, 8.6%, 42.9%, and 22.9%. There were two cases of postoperative superficial
      scleral melting in group C. Otherwise, no major postoperative complications were
      encountered. CONCLUSIONS: The midterm results of a single intraoperative
      application of MMC at the concentration of 0.02% for 5 minutes are encouraging.
      Its application as an adjunctive therapy for the surgical treatment of pterygium
      appeared to be safe and effective. However, because of the possibility of serious
      late complications, the authors suggest that this procedure be reserved for
      patients who have high probability of recurrence after excision of pterygium.

PMID- 9593397
TI  - Digital image processing measurement of the upper eyelid contour in Graves
      disease and congenital blepharoptosis.
AB  - OBJECTIVE: This study used image processing techniques to quantify the upper
      eyelid contour of patients with Graves upper eyelid retraction and congenital
      blepharoptosis. DESIGN: The study design was a cross-sectional study.
      PARTICIPANTS: A total of 29 patients with Graves disease, 22 patients with
      congenital blepharoptosis, and 50 patients with no history of eye disease
      participated. INTERVENTION: The images of the palpebral fissure of all
      participants were transferred to a personal computer and processed with NIH Image
      1.55 software. MAIN OUTCOME MEASURES: The following parameters were analyzed: the
      curvature of the upper eyelid contour, the position of the contour peak relative
      to the midline, and the ratio between the temporal and nasal upper quadrant areas
      of the palpebral fissure. RESULTS: All upper eyelid contours could be fitted with
      second-degree polynomial functions. The mean temporal/nasal area ratio was 1.33
      mm in patients with Graves disease, 0.92 mm in patients with blepharoptosis, and
      1.04 mm in control subjects. The peak of the upper eyelid contour was found to be
      lateral to the midline in control subjects (1.05 mm) and in patients with Graves
      disease (2.09 mm). In patients with blepharoptosis, the peak was 0.69 mm medial
      to the midline. Overall, the distance between the midpupil and the upper eyelid
      margin was correlated with several factors: the degree of curvature, the position
      of the peak of the eyelid contour, and the temporal/nasal area ratio.
      CONCLUSIONS: In Graves eyelid retraction, the curvature of the upper eyelid is
      enhanced, the peak of the contour is displaced laterally, and the temporal upper
      quadrant area is increased. Conversely, in congenital blepharoptosis, the eyelid
      is almost flat, the peak of the contour is displaced medially, and the upper
      quadrant area is diminished. The lateral segment of the upper eyelid is more
      involved than the nasal segment in both Graves upper eyelid retraction and
      congenital blepharoptosis.

PMID- 9593396
TI  - Correlation of high-frequency ultrasound backscatter with tumor microstructure in
      iris melanoma.
AB  - OBJECTIVE: This study aimed to correlate histologic characteristics with high
      frequency ultrasound backscatter spectra in malignant melanomas of the iris.
      DESIGN: The study design was a cohort (case series) study of patients diagnosed
      with iris melanoma in the authors' clinic. PARTICIPANTS: Sixteen patients with
      iris melanoma participated. INTERVENTION: The patients were scanned with a 50-MHz
      ultrasound unit equipped for digitization of raw echo data. Spectral parameter
      images representing the spatial distribution of size and concentration of tissue
      inhomogeneities were produced. MAIN OUTCOME MEASURES: The variation of spectral
      properties within and between tumors was determined. In the two tumors in this
      series for which histologic material was available, the authors compared
      scatterer concentration and size with histology and mathematically modeled the
      effect of melanocyte distribution on spectra. RESULTS: Ultrasound scattering
      characteristics differed considerably among tumors. Where histology was
      available, acoustic parameters correlated with the size and number of melanocytes
      present. CONCLUSIONS: Iris melanomas exhibited a wide range in acoustic
      backscatter properties. Whereas characteristics such as vascularity and necrosis
      might contribute to this, in the two cases examined here, backscatter
      characteristics could be largely accounted for by melanocyte distribution. A
      better understanding of the relationship of histology to noninvasive ultrasound
      data will enhance the diagnostic utility of this technique.

PMID- 9593398
TI  - Enhancement of the cosmetic and functional outcome of enucleation with the
      conical orbital implant.
AB  - OBJECTIVE: The authors evaluated a new design of a conical-shaped enucleation
      implant to help minimize the occurrence of superior sulcus defects and maximize
      motility of the prosthesis. The implant shape is a modification of a sphere. It
      has a posterior conical projection paralleling the orbital walls, a superior
      projection supporting the soft tissues of the upper eyelid sulcus, a flattened
      anterior surface, and channels for each rectus muscle. DESIGN: The study design
      was a consecutive case series from the Oculoplastics and Orbital Service of the
      Massachusetts Eye and Ear Infirmary. INTERVENTION/PARTICIPANTS: A total of 45
      patients (average age, 40 years; range, 13-75 years) had placement of a conical
      implant (39 primary enucleations, 6 secondary implants) with a minimum of 1 year'
      follow-up (range, 12-36 months). All of the primary enucleations and two of the
      secondary procedures had the anterior portion of the implant covered with
      autologous fascia. Four of the secondary implants were covered with pseudocapsule
      harvested from the explanted primary implant. Prostheses were fit 6 to 10 weeks
      after surgery. MAIN OUTCOME MEASURES: Postoperative appearance of patients was
      assessed by qualitative appearance of the superior sulcus and prosthetic
      motility, and subjectively by patients' satisfaction. RESULTS: A total of 43
      patients had minimal or no superior sulcus defect, whereas 2 patients had
      moderate defects. There were no severe sulcus defects. All patients were
      satisfied with their appearance and did not seek further surgery to correct any
      upper sulcus asymmetry. Prosthetic motility with small-angle ductions (<10
      degrees) and saccades was good in all cases. There were two cases of conjunctival
      wound dehiscence. Both occurred within 4 weeks of surgery. One wound dehiscence
      was sutured, whereas the other healed spontaneously. There were no cases of
      implant extrusion, migration, or infection. CONCLUSION: The conical orbital
      implant provides appropriate reconstitution of orbital volume while minimizing
      superior sulcus defects with adequate prosthetic motility.

PMID- 9593399
TI  - Laser thermal keratoplasty for the treatment of photorefractive keratectomy
      overcorrections: a 1-year follow-up.
AB  - OBJECTIVE: To evaluate the results of holmium:YAG laser thermal keratoplasty
      (LTK) treatment for overcorrection of myopia after a photorefractive keratectomy
      (PRK) treatment. PARTICIPANTS: Thirty-six eyes (33 patients) were treated with a
      nontouch holmium:YAG laser (Sunrise Technologies, Model LTK, Freemont, CA)
      because of hyperopia (mean +/- standard deviation of +2.06 diopter [D] +/- 0.75,
      ranging from +1.0 to +3.5 D) following a PRK treatment. A control LTK group
      treated for primary hyperopia, who had preoperative refraction values not
      statistically different from the PRK + LTK group, was used for comparison.
      INTERVENTION: The number of spots applied varied from 8 to 24, and the energy
      used was 200 to 240 mJ. A maximum of three rings of four to eight spots were
      placed between 6 and 8 mm from the visual axis. RESULTS: Twelve months after the
      LTK retreatment for PRK patients, mean refraction was +1.14 D +/- 1.09.
      Regression from 1 to 12 months was 0.5 D +/- 1.1. At 12 months, 50% of eyes were
      within 1 D of emmetropia; 93% of eyes had uncorrected visual acuity (UCVA) of
      20/40 or better; and 24% of eyes had UCVA of 20/20 or better. Refraction was not
      stable for 11 eyes (34%) that regained original sphere values or higher. Best
      corrected visual acuity was not affected, and haze was not increased nor
      decreased by the procedure. CONCLUSIONS: Twelve months after an LTK retreatment
      for an initial PRK, two thirds of the retreated eyes did not need further
      retreatments. However, clinical data showed that LTK should be kept for +1 to +2
      D of hyperopia for PRK overcorrection retreatments.

PMID- 9593400
TI  - Laser in situ keratomileusis for moderate and high myopia and myopic astigmatism.
AB  - OBJECTIVE: This study evaluated the predictability, stability, and safety of
      laser in situ keratomileusis (LASIK) in myopia and myopic astigmatism. DESIGN:
      The study design was a prospective, unmasked, nonrandomized clinical trial.
      PARTICIPANTS: Participating were 25 patients with myopia (37 eyes) with
      astigmatism of less than 1.00 diopter (D), divided into 3 subgroups (-5.00 to 
      9.90 D, 8 eyes; -10.00 to -14.90 D, 10 eyes; -15.00 to -29.00 D, 19 eyes), and 37
      patients with myopia (56 eyes) with corneal astigmatism of 1.00 to 4.50 D,
      divided into 3 subgroups (-5.00 to -9.90 D, 12 eyes; -10.00 to -14.90 D, 24 eyes;
      -15.00 to -29.00 D, 20 eyes). INTERVENTION: LASIK was performed using the
      Automatic Corneal Shaper and the Keracor 116 excimer laser. MAIN OUTCOME
      MEASURES: Visual acuity, manifest refraction, central corneal islands, ablation
      decentration, and patient satisfaction were measured. RESULTS: At 12 months,
      predictability, regression between 1 and 12 months, uncorrected visual acuity
      (UCVA), loss of two or more lines of corrected visual acuity, and patient
      satisfaction of the spherical (toric) groups are reported. Subgroups -5.00 to 
      9.90 D: 100% (75%) +1.00 D; regression less than or equal to 1.00 D in 100%
      (91.7%); UCVA greater than or equal to 20/40 in 87.5% (70%); none lost two or
      more lines; 100% (84%) highly satisfied. Subgroups -10.00 to -14.90 D: 60%
      (78.3%) +/-1.00 D; regression less than or equal to 1.00 D in 100% (87%); UCVA
      greater than or equal to 20/40 in 77.8% (86.4%); 10% (4.3%) lost two lines; 90%
      (91%) highly satisfied. Subgroups -15.00 to -29.00 D: 38.9% (21.4%) +/-1.00 D;
      regression less than or equal to 1.00 D in 72.2% (64.3%); UCVA greater than or
      equal to 20/40 in 33.3% (40%); 5.6% (7.1%) lost two lines; 78% (50%) highly
      satisfied. Differences of predictability and change of manifest refraction
      between subgroups of -5.00 to -9.90 D and -15.00 to -29.00 D were statistically
      significant. Central islands (decentrations) were observed in 17% (5.6%) of eyes
      of the spherical and in 16% (4.1%) of the toric group. Overall, the corneal
      interface was visible in 8.2%. CONCLUSIONS: The LASIK method used in this study
      showed stability of manifest refraction and adequate uncorrected central visual
      acuity in a large percentage of patients with myopia up to -15.00 D. Corneal
      stability was not as uniform. Central corneal islands were observed in a sizable
      minority of patients despite pretreatment. For myopia greater than 15.00 D,
      accuracy and patient satisfaction were sufficiently poor to advise against using
      the authors' treatment technique in these groups. Visually significant
      microkeratome and laser-related problems were noted in a smaller percentage of
      patients. Patients with astigmatism correction were less pleased with results
      than were patients who received spherical corrections.

PMID- 9593401
TI  - Correction of attitudes to prison medicine.

PMID- 9593402
TI  - Surgery for prevention of stroke.

PMID- 9593403
TI  - Insulin-like growth factor-I and new opportunities for cancer prevention.

PMID- 9593404
TI  - Optimism over vaccines administered via mucosal surfaces.

PMID- 9593405
TI  - Chrysotile asbestos: enough is enough.

PMID- 9593406
TI  - Bioterrorism: thinking the unthinkable.

PMID- 9593407
TI  - Randomised trial of endarterectomy for recently symptomatic carotid stenosis:
      final results of the MRC European Carotid Surgery Trial (ECST)
AB  - BACKGROUND: Our objective was to assess the risks and benefits of carotid
      endarterectomy, primarily in terms of stroke prevention, in patients with
      recently symptomatic carotid stenosis. METHODS: This multicentre, randomised
      controlled trial enrolled 3024 patients. We enrolled men and women of any age,
      with some degree of carotid stenosis, who within the previous 6 months had had at
      least one transient or mild symptomatic ischaemic vascular event in the
      distribution of one or both carotid arteries. Between 1981 and 1994, we allocated
      1811 (60%) patients to surgery and 1213 (40%) to control (surgery to be avoided
      for as long as possible). Follow-up was until the end of 1995 (mean 6.1 years),
      and the main analyses were by intention to treat. FINDINGS: The overall outcome
      (major stroke or death) occurred in 669 (37.0%) surgery-group patients and 442
      (36.5%) control-group patients. The risk of major stroke or death complicating
      surgery (7.0%) did not vary substantially with severity of stenosis. On the other
      hand, the risk of major ischaemic stroke ipsilateral to the unoperated
      symptomatic carotid artery increased with severity of stenosis, particularly
      above about 70-80% of the original luminal diameter, but only for 2-3 years after
      randomisation. On average, the immediate risk of surgery was worth trading off
      against the long-term risk of stroke without surgery when the stenosis was
      greater than about 80% diameter; the Kaplan-Meier estimate of the frequency of a
      major stroke or death at 3 years was 26.5% for the control group and 14.9% for
      the surgery group, an absolute benefit from surgery of 11.6%. However,
      consideration of variations in risk with age and sex modified this simple rule
      based on stenosis severity. We present a graphical procedure that should improve
      the selection of patients for surgery. INTERPRETATION: Carotid endarterectomy is
      indicated for most patients with a recent non-disabling carotid-territory
      ischaemic event when the symptomatic stenosis is greater than about 80%. Age and
      sex should also be taken into account in decisions on whether to operate.

PMID- 9593408
TI  - Association of hypertension with T594M mutation in beta subunit of epithelial
      sodium channels in black people resident in London.
AB  - BACKGROUND: Liddle's syndrome is a rare inherited form of hypertension in which
      mutations of the epithelial sodium channel result in increased renal sodium
      reabsorption. Essential hypertension in black patients also shows clinical
      features of sodium retention so we screened black people for the T594M mutation,
      the most commonly identified sodium-channel mutation. METHODS: In a case-control
      study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142
      normotensive (48.7 [7.4] years; 61:81) black people who lived in London, UK, were
      screened for T594M. Part of the last exon of the epithelial sodium-channel beta
      subunit from genomic DNA was amplified by PCR. The T594M variant was detected by
      single-strand conformational polymorphism analysis of PCR products and confirmed
      by DNA sequencing. FINDINGS: 17 (8.3%) of 206 hypertensive participants compared
      with three (2.1%) of 142 normotensive participants possessed the T594M variant
      (odds ratio [OR]=4.17 [95% CI 1.12-18.25], p=0.029). A high proportion of
      participants with the T594M variant were women (15 of 17 hypertensive
      participants and all three normotensive participants), whereas women comprised a
      lower proportion of the individuals screened (61.2% hypertensive, 57.7%
      normotensive). However, the association between the T594M variant and
      hypertension persisted after adjustment for sex and body-mass index (Mantel
      Haenszel OR=5.52 [1.40-30.61], p=0.012). Plasma renin activity was significantly
      lower in 13 hypertensive participants with the T594M variant (median=0.19 ng mL(
      1) h(-1)) than in 39 untreated hypertensive individuals without the variant
      (median=0.45 ng mL(-1) h(-1), p=0.009). INTERPRETATION: Among black London people
      the T594M sodium-channel beta subunit mutation occurs more frequently in people
      with hypertension than those without. The T594M variant may increase sodium
      channel activity and could raise blood pressure in affected people by increasing
      renal tubular sodium reabsorption. These findings suggest that the T594M mutation
      could be the most common secondary cause of essential hypertension in black
      people identified to date.

PMID- 9593409
TI  - Circulating concentrations of insulin-like growth factor-I and risk of breast
      cancer.
AB  - BACKGROUND: Insulin-like growth factor (IGF)-I, a mitogenic and antiapoptotic
      peptide, can affect the proliferation of breast epithelial cells, and is thought
      to have a role in breast cancer. We hypothesised that high circulating IGF-I
      concentrations would be associated with an increased risk of breast cancer.
      METHODS: We carried out a nested case-control study within the prospective
      Nurses' Health Study cohort. Plasma concentrations of IGF-I and IGF binding
      protein 3 (IGFBP-3) were measured in blood samples collected in 1989-90. We
      identified 397 women who had a diagnosis of breast cancer after this date and 620
      age-matched controls. IGF-I concentrations were compared by logistic regression
      with adjustment for other breast-cancer risk factors. FINDINGS: There was no
      association between IGF-I concentrations and breast-cancer risk among the whole
      study group. In postmenopausal women there was no association between IGF-I
      concentrations and breast-cancer risk (top vs bottom quintile of IGF-I, relative
      risk 0.85 [95% CI 0.53-1.39]). The relative risk of breast cancer among
      premenopausal women by IGF-I concentration (top vs bottom tertile) was 2.33 (1.06
      5.16; p for trend 0.08). Among premenopausal women less than 50 years old at the
      time of blood collection, the relative risk was 4.58 (1.75-12.0; p for trend
      0.02). After further adjustment for plasma IGFBP-3 concentrations these relative
      risks were 2.88 and 7.28, respectively. INTERPRETATION: A positive relation
      between circulating IGF-I concentration and risk of breast cancer was found among
      premenopausal but not postmenopausal women. Plasma IGF-I concentrations may be
      useful in the identification of women at high risk of breast cancer and in the
      development of risk reduction strategies. Additional larger studies of this
      association among premenopausal women are needed to provide more precise
      estimates of effect.

PMID- 9593410
TI  - Non-invasive mapping of placental perfusion.
AB  - BACKGROUND: We aim to develop a clinical technique for the non-invasive
      measurement of placental perfusion, to enable early detection of intrauterine
      growth restriction (IUGR). Pregnancies with this complication are characterised
      by low placental perfusion. METHODS: We measured placental perfusion by means of
      perfusion-sensitive echoplanar imaging (EPI); a rapid method of making magnetic
      resonance images. Perfusion measurements were done on six healthy volunteers with
      normal pregnancies and nine with pregnancies complicated by IUGR. Perfusion maps
      were created to assess the relation between placental perfusion and fetal size at
      birth. FINDINGS: Pregnancies complicated by IUGR differed significantly from
      normal pregnancies in patterns of perfusion within the placenta (p<0.0001,
      ANOVA). Subsequent analysis showed that the proportion of placentas with low
      perfusion rates was higher in the IUGR group than in the normal group. A
      significant correlation between areas of reduced placental perfusion and fetal
      size was demonstrated (p=0.041, Spearman's rank correlation). INTERPRETATION: Non
      invasive imaging of placental perfusion by means of EPI has potential as a
      clinical tool in assessing the dynamics of placental perfusion.

PMID- 9593411
TI  - Knee osteoarthritis and high-heeled shoes.
AB  - BACKGROUND: Little is known about the effects of walking in high heels on joints
      in the legs. Since osteoarthritis of the knee is twice as common in women as in
      men, we investigated torques (forces applied about the leg joints) of women who
      wore high-heeled shoes. METHODS: We studied 20 healthy women who were comfortable
      wearing high-heeled shoes. The women walked with their own high-heeled shoes and
      barefoot. Data were plotted and qualitatively compared; major peak values for
      high-heeled and barefoot walking were statistically compared. Bonferroni
      adjustment was made for multiple comparisons. FINDINGS: Measurement showed
      increased force across the patellofemoral joint and a greater compressive force
      on the medial compartment of the knee (average 23% greater forces) during walking
      in high heels than barefoot. INTERPRETATION: The altered forces at the knee
      caused by walking in high heels may predispose to degenerative changes in the
      joint.

PMID- 9593412
TI  - Were there metastases?

PMID- 9593413
TI  - Photodynamic treatment for lower genital tract intraepithelial neoplasia.

PMID- 9593414
TI  - Increased risk of cerebral venous sinus thrombosis with third-generation oral
      contraceptives. Cerebral Venous Sinus Thrombosis Study Group.

PMID- 9593415
TI  - Pregnancies and terminations after 1995 warning about third-generation oral
      contraceptives.

PMID- 9593416
TI  - SimpliRED D-dimer can reduce the diagnostic tests in suspected deep vein
      thrombosis.

PMID- 9593417
TI  - Operating on intracanalicular acoustic neuroma--what would ENT doctors choose for
      themselves?

PMID- 9593418
TI  - Beta-agonist therapy and asthma mortality in Japan.

PMID- 9593419
TI  - Ototoxicity induced by once-daily gentamicin.

PMID- 9593420
TI  - Rotary biopsy forceps.

PMID- 9593421
TI  - Why are cystic-fibrosis mutations so common?

PMID- 9593422
TI  - Pills may replace ear-muffs for protection against damaging noise.

PMID- 9593423
TI  - Laser surgery for eye defects--of proven use or not?

PMID- 9593424
TI  - Algerian abortion controversy highlights rape of war victims.

PMID- 9593425
TI  - National Institutes of Health under attack in budget wrangles.

PMID- 9593426
TI  - Toxic epidermal necrolysis.

PMID- 9593427
TI  - South African health care in black and white. Interview by Gabrielle Murphy.

PMID- 9593428
TI  - Myth and paradox of coronary risk and the menopause.

PMID- 9593429
TI  - Anorexia nervosa: rediscovery of a disorder.

PMID- 9593430
TI  - Statins and fibrinogen.

PMID- 9593431
TI  - Statins and fibrinogen.

PMID- 9593432
TI  - Statins and fibrinogen.

PMID- 9593433
TI  - Statins and fibrinogen.

PMID- 9593434
TI  - Management of hyperactive inattentive children.

PMID- 9593435
TI  - Management of hyperactive inattentive children.

PMID- 9593436
TI  - Management of hyperactive inattentive children.

PMID- 9593437
TI  - Antiretroviral therapy in countries with low health expenditure.

PMID- 9593438
TI  - Safety and fetal outcome of early and midtrimester amniocentesis.

PMID- 9593439
TI  - Safety and fetal outcome of early and midtrimester amniocentesis.

PMID- 9593440
TI  - Safety and fetal outcome of early and midtrimester amniocentesis.

PMID- 9593441
TI  - Conflicting brain images.

PMID- 9593442
TI  - Baroreflex sensitivity and heart-rate variability in insulin-dependent diabetics
      with polyneuropathy.

PMID- 9593443
TI  - Isolation of measles virus from infants in Lusaka.

PMID- 9593444
TI  - Opiates for sickle-cell crisis?

PMID- 9593445
TI  - Shrinking humankind.

PMID- 9593446
TI  - Massachusetts HIV-1 programme.

PMID- 9593447
TI  - Screening for cervical cancer.

PMID- 9593448
TI  - Lessons from Albania.

PMID- 9593449
TI  - Shark cartilage for cancer.

PMID- 9593451
TI  - Adoptive immunotherapy of feline leukemia virus infection using autologous lymph
      node lymphocytes.
AB  - Adoptive immunotherapy using autologous cells expanded ex vivo from lymph nodes
      was examined in cats infected with the retrovirus feline leukemia virus (FeLV).
      Cells were obtained from popliteal lymph nodes from 18 FeLV-antigen-positive cats
      without complications; a mean of 6.2 x 10(7) cells were obtained. Lymph node
      cells were cultured with 600 IU/ml interleukin-2 (IL-2) for 7 days. Cells
      expanded 0.8- to 11-fold (mean, 2.7; median, 2.4); were 80% +/- 8.0% CD3+, 29% +/
      8.1% CD4+, and 41% +/- 7.0% CD8+, and exhibited cytolytic activity against FeLV
      transformed FL74 cells. Sixteen cats received a single intravenous infusion of
      0.13 to 3.9 x 10(8) cells. Cell infusion was well tolerated; fever developed
      approximately 1 hour postinfusion. Clinical activity, antiviral activity, or both
      was observed in 10 cats. Nine cats had clinical responses with improvement in
      weight, activity, appearance, or a combination of these that began 2 to 4 weeks
      after cell infusion and that lasted for up to 13 or more months. FeLV antigen
      became undetectable in 4 cats. These results indicate that adoptive immunotherapy
      using autologous lymph node cells, activated and expanded ex vivo in short-term
      cultures with low concentrations of IL-2, can modulate the course of a retroviral
      infection.

PMID- 9593452
TI  - Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis
      (Arthrospira platensis).
AB  - An aqueous extract of the blue-green filamentous algae Arthrospira platensis
      (previously called Spirulina platensis) inhibited HIV-1 replication in human T
      cell lines, peripheral blood mononuclear cells (PBMC), and Langerhans cells (LC).
      Extract concentrations ranging between 0.3 and 1.2 microg/ml reduced viral
      production by approximately 50% (50% effective concentration [EC50]) in PBMCs.
      The 50% inhibitory concentration (IC50) of extract for PBMC growth ranged between
      0.8 and 3.1 mg/ml. Depending on the cell type used, therapeutic indices ranged
      between 200 and 6000. The extract inactivated HIV-1 infectivity directly when
      preincubated with virus before addition to human T-cell lines. Fractionation of
      the extract revealed antiviral activity in the polysaccharide fraction and also
      in a fraction depleted of polysaccharides and tannins. We conclude that aqueous A
      platensis extracts contain antiretroviral activity that may be of potential
      clinical interest.

PMID- 9593453
TI  - SCID mice with HIV encephalitis develop behavioral abnormalities.
AB  - Severe combined immunodeficient (SCID) mice inoculated intracerebrally (i.c.)
      with HIV-infected human monocytes develop brain pathology similar to that in
      humans with HIV encephalitis. This includes HIV-positive macrophages and
      multinucleated giant cells, astrogliosis, microglial nodules, and neuronal
      dropout. These xenografts survive about 1 month. To develop a model of chronic
      HIV encephalitis and to assay the resulting behavioral abnormalities, we
      reinoculated SCID mice i.c. every 4 weeks for 3 months with either HIV-infected
      human monocytes (n = 5) or uninfected human macrophages (n = 4) or administered
      no inoculation (n = 6); these three groups were monitored for behavioral
      abnormalities. Tests of cognitive function in a Morris water maze 3.5 months
      after the first inoculation suggested that HIV-infected mice performed poorly
      compared with controls. Following testing in the water maze on days 4 and 5 of
      acquisition, motor activity of infected mice was reduced in comparison with that
      of controls. Retention of goal location when tested 1 week later was impaired in
      HIV-infected mice compared with controls. Histopathologic analysis of brains
      revealed significant astrogliosis and strongly suggested higher numbers of major
      histocompatibility complex (MHC) class II-positive multinucleated macrophages in
      HIV-infected compared with control mice. Thus, our preliminary studies indicate
      that SCID mice with HIV encephalitis develop behavioral abnormalities reminiscent
      of human disease. These behavioral abnormalities are associated with
      significantly increased astrogliosis, the presence of HIV, and probably
      multinucleated giant cells. These studies further support the use of this SCID
      animal model system for studies of the pathogenesis of HIV encephalitis and for
      drug interventions.

PMID- 9593454
TI  - Serum retinol and HIV-1 RNA viral load in rapid and slow progressors.
AB  - Few studies have addressed the relation between serum vitamin A level and HIV
      disease progression. Thirty HIV-infected women in Rwanda were studied over a time
      span of 26 to 99 months. Fourteen subjects seroconverted and died of HIV-related
      disease at a mean of 44 months (range, 26-69 months) after their first HIV
      positive test and were termed "rapid progressors," (RPs). A comparison group of
      16 "slow progressors" (SPs) were HIV-positive at the time of their first HIV
      serology and had asymptomatic HIV infections at a mean of 96 months (range, 93-99
      months) after their first HIV serology. Baseline mean serum retinol values were
      the same in RPs and SPs: 0.65 + 0.08 mmol/L versus 0.67 + 0.09 micromol/L (p =
      .7). Lower serum retinol levels were observed in RPs compared with SPs for the
      second and third measurements, obtained at a median of 12 and 24 months past
      baseline: 0.51 + 0.07 mmol/L versus 0.76 + 0.14 mmol/L (p = .3) and 0.44 + 0.09
      mmol/L versus 0.64 + 0.08 mmol/L (p = .08), respectively. Median retinol levels
      for the third sample measurement were similar in RPs with lower viral load (LVL)
      and SPs (0.49 mmol/L and 0.52 mmol/L, respectively) compared with only 0.19
      mmol/L in RPs with higher viral load (HVL; p = .02). A trend toward decreasing
      serum retinol levels and increasing HIV-1 RNA viral load was observed at the
      third sample measurement (p = .04). Subjects with LVL, higher serum retinol
      levels (> or =0.70 mmol/L), or both had more favorable rates of survival than
      subjects with HVL, low serum retinol levels (<0.70 mmol/L), or both. Although
      sample size does not permit definitive conclusions, this study demonstrates an
      association of high HIV load, rapid progression, and low serum retinol late but
      not early in disease progression.

PMID- 9593455
TI  - Fetal, infant, and maternal toxicity of zidovudine (azidothymidine) administered
      throughout pregnancy in Macaca nemestrina.
AB  - The toxicity of azidothymidine (AZT) was studied in monkey dams and fetuses that
      were exposed to the drug over the entire gestational period. Fourteen virus-free
      female macaques (Macaca nemestrina) were randomly assigned to AZT or control
      groups. AZT animals received the drug through a gastric catheter at a dose of 1.5
      mg/kg every 4 hours, which produced plasma concentrations similar to those in
      humans taking 500 to 600 mg/day of AZT. Control animals received water placebo,
      also through gastric catheter. Some animals participated in both groups. All
      females were mated with the same male; 41 matings produced 20 pregnancies, of
      which 16 were carried to term (9 in AZT females; 7 in control females). The AZT
      animals developed an asymptomatic macrocytic anemia, but hematologic parameters
      returned to normal when AZT was discontinued. Total leukocyte count decreased
      during pregnancy and was further affected by AZT administration. AZT-exposed
      infants were mildly anemic at birth. AZT caused deficits in growth, rooting and
      snouting reflexes, and the ability to fixate and follow near stimuli visually,
      but the deficits disappeared over time. These data indicate that early exposure
      to AZT in utero should have no irreversible adverse effects on the fetus.

PMID- 9593456
TI  - Bacterial pneumonia in HIV-infected patients: analysis of risk factors and
      prognostic indicators.
AB  - This case control study assessed risk factors and prognostic indicators of 350
      episodes of bacterial pneumonia in 285 HIV-infected patients. On univariate
      analysis, intravenous drug abuse (i.v.DA; p < .001 versus controls), regular
      cigarette smoking (p < .001), cirrhosis (p = .04), and history of a previous
      episode of pneumonia (p = .04) were risk factors for community-acquired episodes
      of bacterial pneumonia, whereas length of hospitalization (p = .01) was a risk
      factor only for nosocomial bacterial pneumonia. The small amount of circulating T
      CD4+ cells (<100/ mm3) was a risk factor in both groups of pneumonia (p < .05).
      Stepwise logistic regression analysis revealed that i.v.DA in community-acquired
      episodes and low levels of circulating T CD4+ cells, both in community-acquired
      and hospital-acquired episodes, were independent risk factors for the development
      of bacterial pneumonia. The case-fatality rate observed in our study was 27%. On
      stepwise logistic regression analysis, T CD4+ cell counts < or = 100/mm3 (p =
      .02), neutropenia (p = .04), PO2 arterial level < or = 70 mm Hg (p = .01), and
      Karnofsky score < or = 50 (p = .04) were independent indicators of mortality.
      According to a personally developed prognostic score, 211 episodes of pneumonia
      (60%) were classified as mild, 63 (18%) as moderate, and 76 (22%) as severe.
      Clinicians must carefully evaluate those variables that can influence the
      prognosis of bacterial pneumonia to make early identification of affected
      patients and to promptly establish the most appropriate therapeutic strategy in
      each case.

PMID- 9593457
TI  - Foscarnet decreases HIV-1 plasma load.
AB  - OBJECTIVE: To evaluate the effect of foscarnet on HIV-1 replication in vivo.
      PATIENTS AND METHODS: Seventeen AIDS patients with cytomegalovirus (CMV), herpes
      simplex virus (HSV), varicella-zoster virus (VZV) infection, Kaposi's sarcoma
      (KS), or a combination of these were treated with foscarnet. HIV RNA
      quantification (bDNA 2.0, Chiron, Emeryville, CA, U.S.A.), CMV pp65 antigenemia
      (Argene Biosoft, Varilhes, France), and CMV viremia were determined before and
      during therapy. RESULTS: Four patients had CMV retinitis (1 with KS), 2 patients
      had CMV pneumonia (1 with KS), 1 patient had CMV cholecystitis, 2 patients had
      VZV infection (1 with KS), 1 patient had HSV-2 infection, and 7 patients had KS
      alone. The decrease in HIV-1 load was -0.73 +/- 0.39 log copies/ml (p = 2.10(-6))
      after 3 days of treatment and -1.15 +/- 0.49 log copies/ml (p < 10(-7)) after 10
      days of treatment, compared with day 0. Furthermore, reduction of HIV-1 plasma
      load during foscarnet therapy did not depend on the presence or absence of CMV
      disease or on a positive pp65 antigenemia at day 0. CONCLUSION: We observed
      decreased HIV-1 plasma load in all patients treated with foscarnet, regardless of
      presence or absence of clinical or biologic CMV infection. This decrease supports
      the proposition that foscarnet anti-HIV-1 activity may be of clinical importance.

PMID- 9593458
TI  - Pronounced anti-HIV-1 activity of foscarnet in patients without cytomegalovirus
      infection.
AB  - Combined therapy using reverse transcriptase (RT) and protease inhibitors is the
      current established treatment for HIV-1 infection. Foscarnet is an RT inhibitor
      that is a product analogue, in contrast to the widely used nucleoside analogues.
      In this study, the anti-HIV-1 effect of foscarnet, 50 mg three times per day
      administered intravenously for 4 weeks, was evaluated in 10 patients with minor
      or no symptoms. Serious adverse events developed in 2 patients, although most
      patients experienced some side effects. The levels of HIV-1 RNA decreased from a
      median value of 4.7 to 2.6 10log copies/ml. The effect was sustained through 4
      weeks. One week after cessation of treatment, HIV-1 RNA levels increased to
      baseline. In contrast, no increase in the number of CD4+ cells was observed. The
      anti-HIV-1 effect was considered to be a direct effect on HIV-1 replication
      because no patient had concomitant cytomegalovirus (CMV) infection.

PMID- 9593459
TI  - Impact of HIV on families of HIV-infected women who have recently given birth,
      Bangkok, Thailand.
AB  - The objective of this study was to assess changes in the family situation of HIV
      infected women who have recently given birth. As part of a prospective perinatal
      HIV transmission study, interviews were conducted with a subset of HIV-infected
      women at 18 to 24 months postpartum, and answers were compared with baseline
      information obtained during pregnancy. Standardized scales were used to assess
      levels of psychosocial functioning. A convenience sample of 129 HIV-infected
      women enrolled during pregnancy was interviewed at 18 to 24 months postpartum. At
      delivery, the women were young (median age, 22 years), primiparous (57%), and
      asymptomatic (93%). When baseline and follow-up data were compared, more women
      were living alone (1% versus 6%; p = 0.03), fewer women were living with their
      partners (98% versus 73%; p < 0.001), and 30% of families had reduced incomes. At
      follow-up, 10% of partners had died, and more partners than wives had become ill
      or died (21% versus 4%; p = 0.02). Most children (78%) were living with their
      mothers, but only 57% of the HIV-infected women were the primary caretakers.
      Fewer women had disclosed their HIV status to others (e.g., family, friends) than
      to their partners (34% versus 84%; p < 0.001), largely because of fear of
      disclosure. The women appeared to have high levels of depression and worry. The
      women's greatest worries were about their children's health and the family's
      future. Within 2 years after childbirth, substantial change within the families
      of HIV-infected women was evident. These were manifest by partner illness or
      death, family separation, reduced family income, shifting responsibilities for
      child care, and signs of depression and isolation. Providing family support is a
      major challenge in Thailand as the perinatal HIV epidemic progresses.

PMID- 9593460
TI  - Long-term trends in self-reported HIV risk behavior: injection drug users in Los
      Angeles, 1987 through 1995.
AB  - This article reviews trends in self-reported HIV risk behaviors across serial
      samples of injection drug-using (IDU) arrestees interviewed in Los Angeles.
      Between 1987 and 1995, a gradual decrease occurred in the percentage who share
      needles. However, measured over a past-year recall period, the prevalence of
      needle sharing remained high until 1994 to 1995, when it abruptly declined.
      Needle sharing with strangers and needle sharing at shooting galleries declined
      gradually throughout the study period. Among IDUs who shared needles, bleach use
      increased rapidly until 1991 but leveled off thereafter. No change occurred in
      number of sex partners, but condom use gradually increased among IDUs with 2 or
      more partners. Concurrent change in local needle exchange policy and practice may
      explain the abrupt decline in past-year needle sharing. New strategies may be
      needed to promote further increases in bleach use and condom use.

PMID- 9593461
TI  - HIV antibody seroprevalence and associated risk factors in sex workers, drug
      users, and prisoners in Sindh, Pakistan.
AB  - OBJECTIVE: To determine prevalence of HIV infection and risk behaviors in
      commercial sex workers (CSWs), drug users, and prisoners in Sindh, Pakistan.
      METHODS: A medical clinic was established in a "red-light" district of Karachi.
      Eighty-one CSWs who registered at the clinic between November 1993 and June 1994
      were provided HIV counseling and testing and administered a risk factor
      questionnaire. Next, 316 male drug users were tested for HIV-1 antibody from
      April to July 1994. Finally, a voluntary serosurvey of HIV-1 and HIV-2 and risk
      behaviors of 3525 prisoners in Sindh was conducted between July 1994 and December
      1994. Abbott Recombinant HIV third-generation enzyme-linked immunosorbent assay
      (ELISA) and confirmatory testing with Western blot analysis were used in all
      three groups. RESULTS: None of 81 CSWs tested for HIV-1 antibody were positive.
      None of 316 drug users tested positive for HIV-1 antibody. Of 3441 male
      prisoners, 1 was HIV-1 infected, and of 84 female prisoners, 1 was HIV-1
      infected. No prisoner was positive for HIV-2 antibody. DISCUSSION: The prevalence
      of HIV in CSWs, drug users, and prisoners in Sindh is low at present.
      Intervention programs implemented at this stage can make an impact in HIV
      prevention.

PMID- 9593462
TI  - Weight loss as a predictor of survival and disease progression in HIV infection.
      Terry Beirn Community Programs for Clinical Research on AIDS.
AB  - Severe weight loss in HIV is associated with decreased length of survival. It is
      unclear whether mild weight loss is associated with an increased risk of death or
      opportunistic complications of HIV. Participants in four interventional studies
      (n = 2382) conducted by a community-based clinical trials network were evaluated
      for percentage change in weight during their first 4 months in the study.
      Proportional hazards models were performed for the occurrence of opportunistic
      complications and death subsequent to the 4-month visit. The relative risk of
      death and opportunistic complications for those with 5% to 10% weight loss over 4
      months was 2.22 (p < .001) and 1.89 (p < .001), respectively, and 1.26 (p < .01)
      and 1.19 (p < .01) among those who lost 0% to 5% of their body weight,
      respectively, when compared with those with no weight loss. Among those who lost
      5% to 10% of their body weight, the relative risk of individual opportunistic
      complications increased significantly, including Pneumocystis carinii pneumonia
      (PCP) (1.61; p < .01), cytomegalovirus (CMV) (2.33; p < .001), and Mycobacterium
      avium complex (MAC) (1.81; p < .01). As little as 5%t weight loss over a 4-month
      period is associated with increased risk of death and opportunistic complications
      in HIV. A weight loss of 5% to 10% is also associated with an increased risk of
      individual opportunistic complications.

PMID- 9593464
TI  - Trends of AIDS epidemic in Cameroon, 1986 through 1995.

PMID- 9593463
TI  - Cigarette smoking and maternal-child HIV transmission. Women and Infants
      Transmission Study Group.

PMID- 9593465
TI  - Intestinal malabsorption and zidovudine bioavailability.

PMID- 9593466
TI  - Benzene metabolites induce the loss and long arm deletion of chromosomes 5 and 7
      in human lymphocytes.
AB  - Two of the most common cytogenetic changes in therapy- and chemically-related
      leukemia are the loss and long (q) arm deletions of chromosomes 5 and 7 (i.e. -5,
      -7, del(5q) and del(7q)). We have used a novel fluorescence in situ hybridization
      (FISH) procedure to determine if the benzene metabolites hydroquinone (HQ) and
      1,2,4-benzenetriol (BT) can induce these specific changes in human lymphocytes
      cultured as whole blood. Metaphase spreads were prepared and hybridized with
      centromeric probes for chromosomes 1, 5 and 7 and sequence specific probes for
      5q31 and 7q36-qter. HQ and BT significantly increased monosomy 5 and 7 by 3-5
      fold (p < 0.0001). Both HQ and BT also significantly increased the rate of
      del(5q) and del(7q) by 8-12 fold (p < 0.0001). Chromosome 7 was especially
      susceptible to aneusomy induction by HQ and BT at low doses. These results show
      that metabolites of benzene are highly effective in inducing changes in
      chromosomes 5 and 7 that are involved in the development of myeloid leukemia.

PMID- 9593467
TI  - Chronic myelogenous leukemia: effect of interferon-alpha treatment on phagocytic
      activity and capacity of circulating neutrophils.
AB  - This study focuses on the effect of interferon (IFN)-alpha on phagocytosis of
      FITC-labeled Escherichia coli by polymorphonuclear neutrophils (PMNs) in chronic
      myelogenous leukemia (CML). The phagocytic activity and capacity of PMNs from IFN
      alpha treated patients (n = 17), untreated CML patients (n = 9) and from healthy
      donors (n = 20) were compared using flow cytometry. Both parameters of PMN
      phagocytosis were reduced in untreated CML and in IFN-alpha treated CML with Ph1
      chromosome persistence but normal in IFN-alpha treated CML with Ph1 conversion.
      Thus, the phagocytic performance of PMNs in patients with chronic phase CML is
      significantly improved after successful treatment with IFN-alpha.

PMID- 9593468
TI  - Gene transfer of alpha interferon into hematopoietic stem cells.
AB  - Gene transfer or gene therapy has advantages in the treatment of a variety of
      disorders due to its selective expression within specific mammalian cells. IFN
      alpha has been used in the management of leukemia, and gene transfer of the IFN
      alpha gene into hematopoietic progenitor cells may have great potential for the
      treatment of chronic myelogenous leukemia (CML). Therefore, we examined the
      ability of adenovirus (Ad)-IFN-alpha gene construct to transfect normal bone
      marrow hematopoietic CD34+ stem cells and the production of IFN-alpha protein by
      these cells. Ad-cytomegalovirus (CMV) promoter-driven IFN-alpha at multiple doses
      was assessed to transfect highly purified CD34+ cells in liquid culture. Optimal
      transduction of CD34+ cells with the AdCMV-IFN-alpha construct was achieved using
      120 plaque forming units (pfu). Flow cytometric determinations revealed that
      there was no significant difference in CD34+ cell viability for the 8 or 12-h
      transfection periods. Immunoassay of IFN-alpha produced by CD34+ cells shows that
      IFN-alpha levels increased several fold in transfected cells and this was not
      seen in CD34+ cells transfected with the heme oxygenase gene (HO-1). These in
      vitro data suggest that adenovirus-mediated gene transfer of IFN-alpha into
      hematopoietic stem cells can be achieved and that the IFN-alpha protein is
      produced by viable CD34 progenitor cells.

PMID- 9593469
TI  - Correlation of N-ras point mutations with specific chromosomal abnormalities in
      primary myelodysplastic syndrome.
AB  - A cytogenetic and N-ras point mutation study was done in patients with primary
      myelodysplastic syndrome (MDS) from Rio de Janeiro, Brazil, in order to evaluate
      the progression of preleukemic states to overt leukemia. Cytogenetic analysis was
      performed in 50 patients with MDS and clonal chromosomal abnormalities were
      detected in 19 (38%) of them. Patients with refractory anemia (RA) or with ringed
      sideroblasts (RARS) presented normal karyotypes or single abnormalities as
      del(5q) or -Y, while patients in more advanced states as RA with excess of blasts
      (RAEB), RAEB in transformation (RAEB-t) and chronic myelomonocytic leukemia
      (CMML) showed complex karyotypes and single abnormalities involving chromosomes 7
      or 8, which were related to poor prognosis and elevated risk of transformation to
      acute myeloid leukemia (AML). The frequency of ras activation was studied in
      these 50 patients with MDS. Samples of bone marrow were screened for oncogenic
      point mutations by DNA amplification followed by oligonucleotide hybridization
      analysis (PCR-ASO) at codon 12 of N-ras proto-oncogene. We detected N-ras point
      mutations in 21 patients (42%). Progression from MDS to AML was observed in 9
      patients (18%). The correlation analysis between N-ras point mutations and
      specific chromosomal abnormalities indicated that although mutated N-ras was
      found in cells with del(5q) and monosomy 7, cells with those abnormalities and
      normal N-ras were also identified. Otherwise trisomy of chromosome 8 showed a
      correlation with N-ras point mutations and in all cases, patients showed
      progression of MDS to AML during the follow-up study. MDS comprises a
      heterogeneous group of hematopoietic disorders and probably several steps are
      implicated in the evolution to AML. In this work we suggest that one possible
      pathway of leukemogenesis in MDS includes N-ras point mutations in association
      with trisomy of chromosome 8.

PMID- 9593470
TI  - Proto-oncogene expression in bovine peripheral blood leukemic lymphocytes during
      their spontaneous proliferation, differentiation and apoptosis in vitro.
AB  - The expression of various proto-oncogenes in primary culture of lymphocytes from
      peripheral blood of bovine with chronic lymphocytic leukemia (CLL) was studied.
      Cellular proto-oncogenes encode proteins that propagate growth, differentiation
      or apoptosis signals from cell membrane to nucleus. The proliferation and
      differentiation of normal eukaryotic cells are precisely controlled. Tumor cells
      usually are characterized both by the continuous growth signal and by the block
      of cell differentiation. We have previously reported that along with spontaneous
      proliferation, bovine CLL lymphocytes continuously differentiate and enter
      apoptosis in vitro. CLL cells with an autocrine growth mechanism and at the same
      time undergoing spontaneous differentiation and apoptosis in vitro provide a new
      model system to investigate the possible involvement of various proto-oncogenes
      in the regulation of cellular proliferation, differentiation and apoptosis.
      Northern blot analysis revealed simultaneous expression of a number of proto
      oncogenes in CLL cells. Transcripts of c-fos, c-myc, c-myb, A-raf, c-raf1, hck,
      IL-2 receptor alpha-chain (IL-2R alpha) were found in lymphocytes at the peak of
      their proliferative activity in culture. Kinetics studies demonstrated that CLL
      cells constitutively express transcripts of so-called immediate response nuclear
      proto-oncogenes c-myc, c-fos as well as cytoplasmic proto-oncogenes hck and c
      raf1, i.e., genes coding for tyrosine and serine-threonine protein kinases,
      respectively. Expression level did not change significantly during all stages of
      CLL cells in culture. The results show that continuous expression of c-myc mRNA
      does not prevent CLL cell differentiation and may be associated with apoptotic
      cell death.

PMID- 9593471
TI  - Erythropoietin upregulates the expression of its own receptor in TF-1 cell line.
AB  - In the erythroleukemia cell line TF-1, recombinant human erythropoietin (rHEpo),
      but not c-kit ligand, enhanced the number of cells expressing the erythropoietin
      receptor (EpoR), as measured by flow-cytometric analysis of binding of the biotin
      labeled Epo. Moreover, 125I-Epo binding and Scatchard analyses, indicated that TF
      1 cells, maintained in standard conditions with IL-3, and those stimulated with c
      kit ligand, bear a single class of EpoR. On the other hand, cells cultured in the
      presence of rHEpo had a higher number of receptors than IL-3 or c-kit ligand
      stimulated cells, and had two binding sites with different affinities for the
      ligand. EpoR mRNA expression was higher in cells exposed to rHEpo than in IL-3 or
      c-kit-stimulated cells. This difference may have been dependent on either a
      higher level of transcription or an increased stability of mRNA. The observed
      changes of EpoR in rHEpo-stimulated TF-1 cell line could cooperate, together with
      the alteration of the gene (3' end deletion), in the occurrence of the
      erythroleukemic process. Changes induced in EpoR by rHEpo were not accompanied by
      an increase in the expression of glycophorin A or globin chain mRNAs. This may
      suggest that rHEpo is unable to induce erythroid differentiation in TF-1 cells.
      The results also indicate that this cell line could be a model for the
      investigation of the role of transcription factor(s) in the expression of EpoR,
      and for the study of the mechanism(s) underlying the changes in the number and
      affinity of the cell receptors.

PMID- 9593472
TI  - Induction of the differentiation of HL-60 promyelocytic leukemia cells by
      nonsteroidal anti-inflammatory agents in combination with low levels of vitamin
      D3.
AB  - Previous experiments have shown that a variety of agents that interfere with the
      activity of the transcription factor NF-kB significantly enhanced the
      differentiation of HL-60 leukemia cells when combined with low levels of the
      monocytic/macrophagic differentiating agent vitamin D3. These include an
      antisense phosphorothioate oligonucleotide to the Rel A subunit of NF-kB, vitamin
      E and other antioxidants, and curcumin. Acetylsalicylic acid and other
      nonsteroidal anti-inflammatory agents represent another group of agents that have
      been reported to inhibit NF-kB at serum levels approximating those obtained
      during long-term therapy of chronic inflammatory states. To determine whether
      nonsteroidal anti-inflammatory agents also were capable of enhancing the
      differentiation of HL-60 leukemia cells produced by vitamin D3, we measured the
      effects of a variety of nonsteroidal anti-inflammatory agents on the maturation
      of HL-60 cells produced by low levels of vitamin D3. Acetylsalicylic acid by
      itself had no significant effect on the differentiation of HL-60 cells; however,
      this agent markedly increased the degree of differentiation produced by low
      levels of vitamin D3. Furthermore, a variety of other nonsteroidal anti
      inflammatory agents of different chemical classes exhibited similar enhancements
      of the maturation of HL-60 cells when combined with vitamin D3. An analogous
      increase in the differentiation of HL-60 cells was also obtained by combination
      of several nonsteroidal anti-inflammatory agents with the granulocytic inducing
      agent, retinoic acid, but not with dimethylsulfoxide. The nonsteroidal anti
      inflammatory agents also enhanced the differentiation of HL-60 cells when
      combined with vitamin D analogs which share the receptor binding properties of
      vitamin D3; however, a vitamin D analog which caused significant calcium
      mobilization, but was less effective in receptor binding than vitamin D3, did not
      induce the differentiation of HL-60 cells in the presence or absence of anti
      inflammatory agents. The findings suggest that the nonsteroidal anti-inflammatory
      agents may have utility in the treatment of acute promyelocytic leukemia when
      used with the D vitamins or retinoic acid.

PMID- 9593473
TI  - Putative myeloma precursor cells expressing 2,6 sialic acid-modified antigens
      actually belong to the erythroid lineage.
AB  - The Golgi enzyme alpha2,6-sialyltransferase modifies glycoconjugates by adding
      sialic acid. In lymphocytes, different epitopes that result from this
      modification have been identified by the B cell-related CDw75, CDw76, HB4 or HB6
      Ab. We previously described positive staining with these Ab of a highly
      transferrin receptor-positive (CD71) cell type in the bone marrow of multiple
      myeloma patients. These cells were distinct from plasma cells, but did contain Ig
      of the same isotype and idiotype as seen in the plasma cells. We postulated a
      precursor role for this cell type in myeloma. Here, we report that this CD71+
      (HB4/HB6/CDw75/CDw76)+ cell is an erythroid precursor cell instead. RT-PCR did
      not detect Ig mRNA, and from immuno electron microscopy Ig appeared to be
      endocytosed rather than synthesized by these cells. At their cell surface the
      erythroid/megakaryocytic markers CD36 and CD41, and the erythroid-specific
      glycophorin A can be detected, while haemoglobin can be detected antigenically in
      the cytoplasm. Finally, purified cells proliferate in vitro upon addition of
      erythropoietin. Uptake of Ig could be explained by the presence of Fc
      gammaRIII(CD16), which has also been found on other haematopoietic precursor
      cells.

PMID- 9593474
TI  - Peripheral blood lymphocyte subset shifts in patients with untreated
      hematological tumors: evidence for systemic activation of the T cell compartment.
AB  - Flow cytometry immunophenotyping of peripheral blood lymphocyte subsets and
      multivariate data-analytical techniques revealed that among untreated hemato
      oncological patients (n = 48) with lymphomas, acute and chronic myeloid and
      lymphocytic leukemias, monoclonal gammopathy of undetermined significance, and
      multiple myeloma, 42% had (nonmalignant) lymphocyte profiles clearly distinct
      from healthy donors. Notably, a similar pattern of increased CD3+ CD57+, CD3+ HLA
      DR+, CD3+ CD(16 + 56)+, CD4- CD8+, CD8+ CD57+, CD8+ CD28-, and CD8+ CD62L-
      subsets was detected. More extensive three-color immunophenotyping on an
      additional group of 49 untreated patients revealed that both CD4+ and CD8+ T
      cells displayed significant increases of activation markers: CD69, CD(16 + 56),
      HLA-DR, CD71, and CD57, and a loss of CD62L and CD28, which is also interpreted
      as a sign of activation. Consistent with the phenotypical signs of in vivo immune
      activation, polyclonal cytolytic activity, measured ex vivo in an anti-CD3
      redirected assay, was detected within immunomagnetically purified CD4+ T cells of
      three out of six B-CLL patients investigated, but not within purified CD4+ T
      cells of five healthy donors. The purified CD8+ T cells of patients (n = 28) and
      donors (n = 5) on the other hand displayed similar polyclonal cytotoxic
      activities at the various effector:target ratios investigated. Tumor-directed
      cytotoxic activity of purified CD4+ (n = 6) and/or CD8+ T cells (n = 15) against
      freshly isolated autologous tumor cells was not detected in any of the
      experiments. Collectively, our results demonstrate systemic T cell activation as
      a common feature in hematological neoplasia, and a markedly enhanced cytolytic
      activity of the CD4- subset in CLL patients. The reason(s) for this expansion of
      activated T cells and its pathophysiologic significance, however, remain unclear.

PMID- 9593475
TI  - Levels of expression of CD52 in normal and leukemic B and T cells: correlation
      with in vivo therapeutic responses to Campath-1H.
AB  - The CD52 antigen is expressed on most normal and neoplastic lymphoid cells. The
      reshaped humanized IgG1 anti-CD52 monoclonal antibody (Campath-1H) has been used
      in the treatment of hemopoietic and non-hemopoietic diseases for its ability to
      induce lymphocyte depletion both in vitro and in vivo. Good activity has been
      shown in patients with chronic T and B cell leukemias, in particular T
      prolymphocytic leukemia (T-PLL). However, the response to treatment is not
      uniform and this variability may depend on differences in the level of antigen
      expression on the leukemic cells. To test this hypothesis, we used quantitative
      flow cytometry to investigate the intensity of the expression of CD52 in 45 cases
      of lymphoid leukemia, 24 with B-cell chronic lymphocytic leukemia (CLL), 21 with
      T-PLL and 12 normal controls. Normal T lymphocytes expressed higher CD52 antigen
      than B lymphocytes (p < 0.005) and the antigen was also significantly higher in T
      PLL compared to CLL (p < 0.001). Moreover, the differences in CD52 expression
      were somewhat higher in Campath-1H treated patients who responded than in non
      responders. Although other factors may play a role in the response to Campath-1H
      in vivo, the quantitative estimation of CD52 expression may provide a rationale
      for the greater response in T-PLL and help select those patients with a higher
      probability of responding to this therapy.

PMID- 9593476
TI  - Hepatitis B vaccination in acute lymphoblastic leukemia.
AB  - Active immunization against hepatitis B virus infection was carried out in 162
      patients with acute lymphoblastic leukemia attending the Outpatient Department at
      Tata Memorial Hospital. Recombinant DNA vaccine was given in three doses at 0, 1
      and 2 months followed by a booster 1 year after the first dose. Antibodies to
      hepatitis B surface antigen could be detected in 19.7% of patients following
      vaccination. Of these only 10.5% had titers in the protective range.
      Immunosuppression induced by both disease and treatment appears to diminish
      responsiveness to vaccination. Passive active prophylaxis with both vaccine and
      immunoglobulin may be a more effective alternative in these patients.

PMID- 9593477
TI  - Unusual relapse of adult T-cell leukemia/lymphoma after spontaneous remission.
AB  - A 42-year-old man was diagnosed with acute adult T-cell leukemia/lymphoma
      (ATL/L). Abnormal peripheral blood cells (45% of white blood cells) (Fig. 1a),
      hypercalcemia, and systemic lymphadenopathy were observed. Flow cytometric
      analysis (FCM) using peripheral mononuclear cells (PMNC) revealed that the
      immunophenotype of tumor cells was CD4+ CD8- CD25+ CD45RA- CD45RO+. Nevertheless,
      he developed a spontaneous remission 6 months later. At remission, the number of
      CD4-, CD25-, and CD45RO-positive cells decreased, while CD8- and CD45RA-positive
      cells increased to normal levels as previously reported by Suzuki et al. [1]. He
      was then referred to the outpatient clinic where he was periodically evaluated
      and received no therapy. Because of a serious sense of fullness he was re
      admitted 30 months after diagnosis. Physical examination revealed ascites and
      small lymphadenopathy in the right axilla. Atypical lymphoid cells were not
      observed on microscopic examination of the blood smear. FCM using PMNC revealed
      that CD4+ CD25+ cells (3%) were within the normal range. Serum calcium was also
      within the normal range. Abdominal ultrasound examination showed massive ascites.
      Paracentesis demonstrated that the ascitic fluid had a high white blood cell
      count (3.15 x 10(9)/l) with a marked increase in abnormal large cells (Fig. 1b).
      FCM using mononuclear cells in the fluid revealed that 87.3% of the cells were
      double-positive for CD4 and CD25. Southern blot analysis of the cells confirmed
      monoclonal integration of human T-lymphotropic virus type 1 (HTLV-1) proviral
      DNA. The integrated genome was considered to be identical with that detected at
      initial presentation (Fig. 2). A diagnosis of relapsed ATL/L, with the same clone
      as was detected at initial diagnosis, was made. Although he was treated with
      cytotoxic drugs, he did not respond and he died of renal failure 1 month after
      relapse. Autopsy revealed nodular invasive lesions at the rectovesical pouch,
      omentum, diaphragm, and pericardium with peritoneal dissemination.

PMID- 9593478
TI  - CD56 expression in B-cell lymphoma.

PMID- 9593479
TI  - Invasive pneumococcal infection in South and West England.
AB  - Variation in the incidence of invasive pneumococcal disease across South and West
      England, in 1995, was measured through a survey of microbiology laboratories. A
      100% response rate was achieved. The incidence by laboratory varied between 5.2
      and 20.4 per 100,000 catchment population (P < 0.001). Adjusting for pneumococcal
      vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture
      system used and for the age and sex structure of the population, did not account
      for this variation. When blood culture sampling rates were included in a logistic
      regression model, the variation between laboratories was much less and of lower
      statistical significance (P = 0.019). Higher rates of blood culture sampling were
      associated with a higher incidence of invasive pneumococcal disease. Consistently
      high sampling should be encouraged because a higher diagnostic rate should result
      in more selective prescribing of antibiotics, and secondly because improved
      ascertainment of severe pneumococcal infections is a prerequisite for the
      evaluation of new pneumococcal conjugate vaccines.

PMID- 9593480
TI  - National outbreak of Salmonella senftenberg associated with infant food.
AB  - Eight cases of Salmonella senftenberg infection in infants were identified in the
      first half of 1995 in England, five were indistinguishable S. senftenberg
      strains. A case-control study showed an association between illness and
      consumption of one brand of baby cereal (P = 0.03). The cereal manufacturer
      reported isolating S. senftenberg in June 1994 from an undistributed cereal
      batch. Outbreak strains and the cereal strain were all plasmid-free in contrast
      to other human isolates of S. senftenberg in the same period. Changes in the
      production process were implemented to prevent further contamination.
      Surveillance centres should strengthen the detection and investigation of
      outbreaks of gastrointestinal infection in susceptible groups, especially young
      children. In this outbreak, the study of only five cases led to identification of
      the vehicle of infection. Even when few cases are reported, epidemiological
      investigation in conjunction with molecular typing may lead to public health
      action which prevents continuing or future outbreaks.

PMID- 9593482
TI  - Acinetobacter bacteremia in patients with diarrhoeal disease.
AB  - In 1994, 171 (27%) of all positive blood cultures in our hospital were due to
      Acinetobacter species. Of these, 138 cultures were considered significant, 91
      (66%) were community-acquired and 47 (34%) were nosocomial. Most acinetobacter
      bacteraemia in children < or = 1 year old was community-acquired, while
      nosocomial infection was more common in children > 1 year old (P = 0.01). Most
      children < or = 5 years old were severely malnourished. The incidence of
      bacteraemia was lowest during the post-monsoon to early winter months.
      Acinetobacter bacteraemia associated mortality was twice (16%) that of all other
      patients (7.7%, P < 0.0005) and accounted for 4.5% of all hospital deaths during
      the study period. Bacteraemia caused by Acinetobacter species is an important
      cause of morbidity and mortality among our patient population with diarrhoeal
      disease.

PMID- 9593481
TI  - Risk factors for typhoid fever in an endemic setting, Karachi, Pakistan.
AB  - We conducted a study to evaluate risk factors for developing typhoid fever in a
      setting where the disease is endemic in Karachi, Pakistan. We enrolled 100 cases
      with blood culture-confirmed Salmonella typhi between July and October 1994 and
      200 age-matched neighbourhood controls. Cases had a median age of 5.8 years. In a
      conditional logistic regression model, eating ice cream (Odds ratio [OR] = 2.3;
      95% confidence interval [CI] 1.2-4.2, attributable risk [AR] = 36%), eating food
      from a roadside cabin during the summer months (OR = 4.6, 95% CI 1.6-13.0; AR =
      18%), taking antimicrobials in the 2 weeks preceding the onset of symptoms (OR =
      5.7, 95% CI 2.3-13.9, AR = 21%), and drinking water at the work-site (OR = 44.0,
      95% CI 2.8-680, AR = 8%) were all independently associated with typhoid fever.
      There was no difference in the microbiological water quality of home drinking
      water between cases and controls. Typhoid fever in Karachi resulted from high
      dose exposures from multiple sources with individual susceptibility increased by
      young age and prior antimicrobial use. Improving commercial food hygiene and
      decreasing unnecessary antimicrobial use would be expected to decrease the burden
      of typhoid fever.

PMID- 9593483
TI  - Review of the evidence for the use of erythromycin in the management of persons
      exposed to pertussis.
AB  - We assessed the quality of evidence for the use of erythromycin in preventing
      secondary transmission of pertussis to close contacts of primary cases. A
      literature search was undertaken and identified papers were reviewed critically.
      Thirteen original papers and 1 manuscript met the inclusion criteria for review
      (3 randomized controlled trials, 4 analytical studies and 7 descriptive studies).
      Evidence from both experimental and analytical studies showed little effect of
      the use of erythromycin in preventing secondary transmission. Its effect is at
      best modest when compared with the protection conferred by use of good quality
      whole cell vaccine. Three studies reported adverse events with erythromycin
      prophylaxis; these were mainly nausea, vomiting and abdominal pain. In countries
      where effective pertussis vaccines are in use, erythromycin use should be
      confined to close contacts of cases, particularly unimmunized children or
      partially immunized infants who would be most susceptible to the complications of
      pertussis, or adults who come into close contact with vulnerable children.

PMID- 9593484
TI  - Prevalence of Helicobacter pylori infection in a cohort of Italian military
      students.
AB  - In 1990, to study regional prevalences and risk factors of Helicobacter pylori
      infection in healthy young adult males, sera were collected from a nationwide
      sample of 1659 males (mean age 20.7 years) at introduction into the Air Force
      School for military students in Caserta, Italy. An enzyme-linked immunosorbent
      assay was used to detect H. pylori specific immunoglobulin G antibodies. The
      observed overall seropositivity rate was 17.5% (95% CI 15.7-19.4). Prevalence was
      higher in southern Italy and in the Italian islands as compared with northern
      Italy and central Italy (21.3% vs. 9.5%). Multiple logistic regression analysis
      showed that residence in southern areas and islands was the strongest predictor
      of the likelihood of H. pylori seropositivity; number of siblings in the
      household was marginally associated; years of father's schooling was not a
      significant predictor. H. pylori positive subjects were more likely positive for
      antibodies to hepatitis A virus infection (anti-HAV) than those H. pylori
      negative (35.4% vs. 24.9%; Odds Ratio 1.7, 95% CI 1.3-2.2). Adjustment for the
      confounding effect of sociodemographic variables weakened this association (OR
      1.3, 95% CI 1.0-1.7). These findings suggest that differences in environmental
      conditions rather than in socioeconomic status may have played the major role in
      the different spread of H. pylori infection across the country.

PMID- 9593485
TI  - Molecular characterization of Coxiella burnetii isolates.
AB  - Restriction fragment length polymorphism (RFLP) was used for the differentiation
      of 80 Coxiella burnetii isolates derived from animals and humans in Europe, USA,
      Africa and Asia. After NotI restriction of total C. burnetii DNA and pulsed field
      gel electrophoresis (PFGE) 20 different restriction patterns were distinguished.
      The index of discrimination for this typing system was 0.86. Comparison and
      phylogenetic analysis of the different RFLP patterns revealed evolutionary
      relationships among groups that corresponded to the geographical origin of the
      isolates. This finding was confirmed by genetic mapping. No correlation between
      restriction group and virulence of isolates was detected.

PMID- 9593486
TI  - Rabies in Thailand.
AB  - The prevalence of canine and human rabies in Thailand has decreased significantly
      during the last decade. This has been associated with an increasing number of
      human post-exposure treatments. Educational efforts, mass vaccination of dogs and
      cats and the use of safe and effective vaccines have all made an impact. The
      proportion of fluorescent antibody positive dogs, among those examined for rabies
      averaged 54% indicating that rabies is still a major public health threat. Canine
      rabies vaccination is not usually performed in animals < 3 months old. However,
      this study revealed that 14% of rabid dogs were < 3 months old and 42% were < or
      = 6 months old. This is the age group most likely to interact with humans and
      other dogs. Our study also supports the World Health Organization's
      recommendation that observing suspected rabid dogs for 10 days is an adequate and
      safe practice.

PMID- 9593487
TI  - Prevalence of HIV, syphilis and genital chlamydial infection among women in north
      west Ethiopia.
AB  - The prevalence of sexually transmitted diseases (STD) among women visiting
      antenatal (ANC) and gynaecological clinics in Gondar, north-west Ethiopia, was
      investigated. Between April and August 1995, 728 women consented to enter the
      study. Prevalence rates were 5.9% (41/693) for chlamydial antigen in cervix,
      18.8% (113/600) for syphilis (Treponema pallidum haemagglutination assay [TPHA])
      and 25.3% (150/593) for HIV. Active syphilis (RPR)+, TPHA+ was detected in 74%
      (44/597). HIV infection rate was higher among women with higher age of first
      marriage and low gravidity. It was significantly associated with young age, urban
      residence, and presence of genital ulcer (odds ratio [OR] = 6.3), and
      lymphadenopathy (OR = 2.8) on examination. Women seropositive for syphilis had
      married at an earlier age, were significantly older and had changed husbands. Low
      gravidity and age < 30 were independently significant risk factors for cervical
      chlamydial antigen positivity which was predominantly asymptomatic. Significant
      association was observed between HIV infection and syphilis (OR = 2.6). Active
      syphilis was associated with chlamydial (OR = 3.4) and HIV infection (OR = 4.1).
      The rate of 23.4% and 15.1% of HIV seropositivity among ANC attenders and rural
      women respectively is an indicator of the rapid progression of the HIV epidemic
      in the area.

PMID- 9593488
TI  - An epidemiologic study of herpes simplex virus type 1 and 2 infection in Japan
      based on type-specific serological assays.
AB  - A seroepidemiologic study of herpes simplex virus type 1 (HSV-1) and 2 (HSV-2)
      was performed on Japanese adults. Serum samples collected between 1985-9 from a
      total of 536 healthy adults, female prostitutes, males with sexually transmitted
      diseases (STD), homosexual men, and pregnant women were studied by immunodot
      assays using HSV type-specific antigens, glycoproteins G (gG1 and gG2). HSV-1
      infections correlated mostly with age and was widely prevalent among subjects <
      40 years. HSV-2 prevalence varied greatly among subgroups defined by sexual
      activity and was associated with risk behaviours for prostitution, infection with
      STD, and homosexual activity. HSV-2 seroprevalence was highest among prostitutes
      (80%), lowest among pregnant women (7%), and intermediate in STD patients (23%)
      and homosexuals (24%). Because HSV-1 infection during childhood has been
      decreasing, primary genital HSV-2 infection, with its higher frequency of
      clinical manifestations, will become a greater burden to the public health in
      Japan.

PMID- 9593489
TI  - Studies of the presence of verocytotoxic Escherichia coli O157 in bovine faeces
      submitted for diagnostic purposes in England and Wales and on beef carcases in
      abattoirs in the United Kingdom.
AB  - A survey of beef carcases in abattoirs in the UK was carried out in order to
      estimate the prevalence of contamination with verocytotoxin-producing Escherichia
      coli (VTEC) serogroup O157. Contamination with verocytotoxin-producing E. coli
      (VTEC) O157 was confirmed in 0.47% of the 4067 (95% confidence limits 0.22-1.00%)
      of neck muscle samples. A significant tendency for carcases present in the same
      abattoir on the same day to have similar results was found, thus suggesting cross
      contamination. VTEC O157 was found in 0.83% of 6495 bovine faeces samples
      routinely submitted for diagnostic purposes to Veterinary Investigation Centres
      in England and Wales. Of the samples from cattle less than 6 months old, 3.7% of
      68 samples from animals without gastrointestinal disease were positive for E.
      coli O157, in contrast to 0.75% of 2321 samples from cases of gastrointestinal
      disease. No association with season or herd type (beef or dairy) was found.

PMID- 9593490
TI  - The Clostridium perfringens enterotoxin from equine isolates; its
      characterization, sequence and role in foal diarrhoea.
AB  - During a survey of foal diarrhoea between 1991 and 1994, Clostridium perfringens
      was significantly associated with disease with 56% of cases infected [1]. The
      contribution of enterotoxigenic C. perfringens to this association, was assessed
      by use of the reverse passive latex agglutination test for enterotoxin (RPLA;
      Oxoid Unipath) and vero cell toxicity neutralized by antitoxin on stored faecal
      samples and sporulated faecal isolates of C. perfringens. Polymerase chain
      reaction (PCR1) based on the DNA sequence for the whole enterotoxin gene [2]
      yielded a fragment from an equine isolate of the anticipated size which, cloned
      into plasmid M13 phage, had a sequence essentially identical to the published
      sequence. Consequently, all faecal isolates were also tested by PCR1 and for a
      part of the enterotoxin gene (PCR2). Significant association with diarrhoea
      (controls not in contact with cases) was found with positive RPLA tests on faeces
      (OR = 13, P = 0.002) and isolates (OR = 4.57, P = < 0.0001), vero cell toxicity
      of isolates (OR = 1.78, P = 0.026), and PCR1 (OR = nd, P = 0.029) but not PCR2 or
      vero cell toxicity of faeces. Significant association with diarrhoea was also
      found for isolates negative by RPLA (OR = 3.91; CI 2.05-7.57; P < 0.0001) or PCR1
      (OR = 4.81; CI 2.84-8.20; P < 0.0001). Many of the isolates from RPLA positive
      faeces and verotoxic isolates were PCR negative and no evidence could be found
      for the presence of the enterotoxin gene in a random selection of RPLA
      positive/PCR negative isolates by gene probe on chromosomal DNA and PCR reaction
      product or vero cell toxicity neutralized by specific antiserum. Failure of the
      vero cell toxicity on faeces to be associated with diarrhoea or for cytotoxicity
      of cultures and RPLA on cultures to agree with the PCRs was believed to be
      related to the presence of other cytotoxins, the inherent cytotoxicity of equine
      faeces and to the poor specificity of the commercial antiserum used in the test.
      Enterotoxigenic C. perfringens could not account for the overall association of
      C. perfringens with foal diarrhoea because (a) cultures positive by PCR, RPLA or
      cytotoxicity were not significantly more common amongst isolates from cases than
      controls; and (b) the proportion of isolates from cases positive by PCR (PCR1 or
      PCR2) was too small at 9.7%.

PMID- 9593491
TI  - The use of pulsed-field gel electrophoresis to examine the epidemiology of
      Bordetella bronchiseptica isolated from cats and other species.
AB  - A collection (164) of isolates of Bordetella bronchiseptica made predominantly
      from cats (132) but also from dogs (15), pigs (12) and other species was examined
      by pulsed field gel electrophoresis following macrorestriction digestion with
      XbaI. Each isolate was analysed twice and the patterns were entirely
      reproducible. The isolates fell into 17 different strains (> 3 bands different)
      and within strains there were numerous subtypes. Feline isolates fell into 12 of
      the 17 strains. In general, cats housed together had similar or identical strains
      and subtypes of B. bronchiseptica. There was no difference in the PFGE patterns
      of isolates made from carrier cats and those from cats with respiratory disease.
      Isolates from pigs and dogs were in general similar to the feline isolates and
      there was no great evidence for species specificity. The PFGE pattern of feline
      and canine isolates were more related to whether the animals were housed together
      rather than whether they came from dogs or cats.

PMID- 9593492
TI  - Dorsal rhizotomy and physical therapy.

PMID- 9593493
TI  - Selective dorsal rhizotomy: efficacy and safety in an investigator-masked
      randomized clinical trial.
AB  - The objective of this single-center investigator-masked randomized clinical trial
      was to investigate the efficacy and safety of selective dorsal rhizotomy (SDR) in
      children with spastic diplegia. Forty-three children with spastic diplegia were
      randomly assigned on an intention-to-treat basis to receive SDR plus physical
      therapy (PT), or PT alone. Thirty-eight children completed follow-up through 24
      months. Twenty-one children received SDR (SDR+PT group) and 17 received PT (PT
      Only group). SDR was guided with electrophysiological monitoring and performed by
      one experienced neurosurgeon. All subjects received equivalent PT. Spasticity was
      quantified with an electromechanical torque measurement device (spasticity
      measurement system [SMS]). The Gross Motor Function Measure (GMFM) was used to
      document changes in functional mobility. Primary outcome measures were collected
      at baseline, 6, 12, and 24 months by evaluators masked to treatment. At 24
      months, the SDR+PT group exceeded the PT Only group in mean reduction of
      spasticity by SMS measurement (-8.2 versus +5.1 newton meters/radian, P=0.02).
      The SDR+PT group and the PT Only group demonstrated similar improvements in
      independent mobility on the GMFM (7.0 versus 7.2 total percent score, P=0.94).
      Outcomes on secondary variables were consistent with primary outcomes. There were
      no serious adverse events. We conclude that SDR is safe and reduces spasticity in
      children with spastic diplegia. SDR plus PT and equivalent PT without SDR result
      in equal improvements in independent mobility at 24 months. SDR may not be an
      efficacious treatment for children with mild spastic diplegia.

PMID- 9593494
TI  - Electrophysiological monitoring during selective dorsal rhizotomy, and spasticity
      and GMFM performance.
AB  - The relation between abnormal electrophysiological responses to intraoperative
      stimulation during selective dorsal rhizotomy (SDR) and the degree of spasticity
      and motor dysfunction was explored in 92 children with spastic cerebral palsy
      (CP) who underwent SDR at a single center. The proportion of abnormally
      responding rootlets was compared with the degree of spasticity measured with the
      modified Ashworth Scale (MAS) and with the spasticity measurement system (SMS) at
      discrete segmental levels. Motor impairment measured with the Gross Motor
      Function Measure (GMFM) was also compared with the proportion of abnormally
      responding dorsal rootlets. A consistent relation between the proportion of
      abnormally responding rootlets and the degree of spasticity and gross motor
      abnormality at the corresponding muscles could not be demonstrated. There was
      also no consistent association between the proportion of rootlets ablated during
      SDR and the change in spasticity measured with the MAS and SMS, or to the change
      in motor function as measured with the GMFM. These data suggest that the
      intraoperative monitoring technique most commonly used for SDR is unlikely to
      identify accurately those neural elements which contribute to spasticity in
      children with CP.

PMID- 9593495
TI  - Evaluation of selective dorsal rhizotomy for the reduction of spasticity in
      cerebral palsy: a randomized controlled tria.
AB  - Selective dorsal rhizotomy (SDR) is widely used to treat spasticity in children
      with diplegic cerebral palsy (CP) but has never been shown conclusively to
      improve functional outcome. The study was designed to measure changes in gross
      motor function in children 1 year following rhizotomy compared with a control
      group receiving equivalent physiotherapy (PT) and occupational therapy (OT) with
      the exception that the rhizotomy group initially underwent a 6-week postoperative
      in-patient therapy program. Twenty-four children (mean age 58 months) with mild
      to moderate CP with spastic diplegia were randomly assigned to a therapy-only
      control group (CG) (N=12) or rhizotomy and therapy group (RG) (N=12). The Gross
      Motor Function Measure (GMFM) was administered at the baseline, 6-, and 12-month
      assessments. Extremity tone, range of motion (ROM), biomechanics of the ankle
      stretch reflex, isometric contraction, and temporal gait components were also
      evaluated. GMFM scores in the RG improved by 12.1 percentage points versus 4.4
      percentage points in the CG (P<0.02). RG knee and ankle tone was significantly
      reduced (P<0.005), associated with increased passive ankle ROM (P<0.001), and
      decreased soleus EMG reflex activity on forced dorsiflexion (P<0.008). Foot-floor
      contact pattern improved in the RG compared with the CG (P<0.05). In conclusion,
      SDR combined with PT and OT leads to significantly greater functional motor
      improvement at 1 year following surgery compared with PT and OT alone. This was
      achieved in part through reduced knee and ankle tone, increased ankle
      dorsiflexion ROM, and more normal foot-floor contact during walking.

PMID- 9593496
TI  - Academic achievement in children with epilepsy or asthma.
AB  - The purposes of the study were to compare academic achievement between children
      with epilepsy and those with asthma and to identify child perception, school
      adaptive functioning, and condition severity factors related to academic
      achievement. Subjects were 225 children (117 with epilepsy and 108 with asthma)
      aged between 8 and 12 years. Academic achievement was measured using school
      administered group tests. Self-report questionnaires were used to measure child
      attitudes and school self-concept. Teachers rated school adaptive functioning.
      Data were analyzed using ANCOVA and multiple regression. Children with epilepsy
      had significantly lower achievement scores than children with asthma. Boys with
      severe epilepsy were most at risk for underachievement. Factors related to poor
      academic achievement in both samples were: high condition severity, negative
      attitudes, and lower school adaptive functioning scores. Less variance was
      accounted for in the model for epilepsy (R2=0.25) than for asthma (R2=0.36). Boys
      with high seizure severity were most at risk for achievement-related problems.
      Future research in epilepsy should consider additional factors in the model
      predicting academic achievement.

PMID- 9593497
TI  - Can cerebral MRI at age 1 year predict motor and intellectual outcomes in very
      low-birthweight children?
AB  - This follow-up study reports on cerebral MRI findings in 20 very-low-birthweight
      (VLBW) infants without disabilities at age 1 year in relation to motor,
      intellectual, and perceptual function at age 6 years. MRI findings,
      anthropometrics, and Bayley Scales of Infant Development scores at age 1 year as
      predictors of psychomotor status at age 6 years are also evaluated and compared.
      Outcome parameters were the Peabody Developmental Motor Scales and the Wechsler
      Preschool and Primary Scale of Intelligence. The results show that infants with
      myelin hyperintensities including the centrum semiovale or with occipital
      hyperintensities with associated ventricular dilatation at age 1 scored lower on
      the Peabody Gross Motor Locomotion Scale at age 6 than infants with normal
      myelination or with isolated occipital hyperintensities. This may indicate damage
      to motor fibers caused by perinatal periventricular leukomalacia. No relation was
      found between abnormal MRI findings at age 1 and later fine motor, intellectual,
      and perceptual function. Comparing different age 1-year predictors, an
      abnormality score defined by MRI was used as an independent predictor of gross
      motor locomotion function at age 6 years. However, the Bayley Mental Development
      Index scores and weight at age 1 were more important predictors of later motor
      and intellectual outcome, respectively, than MRI findings. It is recommended that
      cerebral MRI should not be used routinely to examine VLBW infants without
      disabilities at 1 year of age.

PMID- 9593498
TI  - Transient nystagmus in delayed visual maturation.
AB  - Two infants who presented with wide-amplitude and high-frequency nystagmus and
      lack of visual awareness in the first 3 months of life were studied. No ocular
      abnormalities were found. Neurodevelopmental examination, visual evoked
      potentials and electroretinograms were normal. One infant underwent MRI which
      resulted in normal findings. Two months later both patients showed increased
      visual responsiveness and a gradual reduction of the nystagmus amplitude. By 5
      months of age nystagmus was no longer detectable and both infants appeared to be
      visually, developmentally, and neurologically normal. Follow-up at 3 years of age
      for subject 1 and at 11 months for subject 2 showed that both the infants
      maintained the normal ophthalmological and neurological assessments. We diagnosed
      delayed visual maturation with oculomotor involvement.

PMID- 9593499
TI  - Epidermoid tumours associated with lumbar punctures performed in early neonatal
      life.
AB  - Three children (ages 5, 7, and 12 years) with epidermoid tumours in the spinal
      canal, all of whom had a lumbar puncture during the early neonatal period, are
      reported. A considerable delay occurred from the first symptoms until the
      diagnosis was made. MRI of the lumbar spine was the method of choice in the
      diagnostic work-up. All three cases were successfully surgically treated. The
      link between lumbar punctures and epidermoid tumours and the possible risk
      factors involved are explored. Because of the variable clinical presentation, the
      possibility of the existence of these tumours should be considered in the
      differential diagnosis.

PMID- 9593500
TI  - The motor unit in cerebral palsy.

PMID- 9593501
TI  - Resolution: a 15-year-old with spastic quadriplegia and a 60 degree scoliosis
      should have a posterior spinal fusion with instrumentation. The American Academy
      for Cerebral Palsy and Developmental Medicine 50th anniversary meeting debate.

PMID- 9593502
TI  - Paediatric nursing and education students' attitudes toward children with Rett
      syndrome: a pilot study.

PMID- 9593503
TI  - Is there an agreed treatment for children in status epilepticus?

PMID- 9593504
TI  - Modulation of ipsilateral motor cortex in man during unimanual finger movements
      of different complexities.
AB  - To understand the role of the ipsilateral motor cortex in the control of
      unimanual movements, we evaluated changes in cortical motor evoked potentials
      (MEP) from the left abductor pollici brevis (APB) to transcranial magnetic
      stimulation (TMS) of the right hemisphere in nine normal subjects during
      execution of right finger movements of different complexities. The motor tasks
      were (a) repetitive opposition movement (thumb tapping the 3rd finger); (b)
      isolated finger movements in a 'usual' sequence (thumb tapping fingers 2, 3, 4
      and 5) and (c) in an 'unusual' sequence (thumb tapping fingers 3, 5, 2 and 4).
      Subjects were trained before the study up to disappearance of EMG synkinetic
      activity in the left APB. As compared to the rest condition, MEP amplitude was
      enhanced in all subjects during paradigm (b) and even more during (c), but
      remained unchanged during paradigm (a). The MEP increase disappeared in four out
      of the nine subjects undergoing overtraining. No significant modifications in MEP
      amplitude were found in the left proximal muscle (biceps, five subjects). The H
      reflex induced by left median nerve stimulation at the elbow (four subjects) and
      MEPs from the left APB to transcranial electrical stimulation (three subjects)
      were not significantly affected by any of the motor paradigms, indicating that
      the motor cortex was the site of change. These results provide evidence of an
      increased excitability of cortical motor outputs targeting the unmoving hand
      muscles during contralateral sequential finger movements which disappears with
      overtraining. We conclude that during motor learning there is an interhemispheric
      transfer of information, possibly in order to inhibit the opposite hemisphere
      from interfering when a fine unimanual movement is required.

PMID- 9593505
TI  - An interleukin-1 receptor fragment blocks ambient temperature-induced increases
      in brain temperature but not sleep in rabbits.
AB  - The effects of intracerebroventricular injection (i.c.v.) of an interleukin-1 (IL
      1) inhibitor, a soluble IL-1 receptor fragment (IL-1RF), on sleep and brain
      temperature (Tbr) responses of rabbits induced by mild increases in ambient
      temperature (Tamb) were determined. Each rabbit was recorded under three
      conditions: (1) 21 degrees C Tamb plus pyrogen-free saline (PFS); (2) 27 degrees
      C Tamb plus PFS; (3) 27 degrees C Tamb plus the IL-1RF. The higher Tamb
      significantly increased Tbr during the warming period; this effect was attenuated
      by pretreatment with the IL-1RF. The higher Tamb alone (6 h exposure)
      significantly increased non-rapid eye movement sleep (NREMS) across the 23-h
      recording period. However, during the 6-h warming period NREMS values, obtained
      after IL-1 RF treatment, were not significantly different from those obtained
      from PFS-treated animals at 27 degrees C Tamb. The ability of the IL-1 RF to
      block Tamb-induced changes in Tbr and the failure of the IL-1RF to block Tamb
      induced NREMS responses is different from previous results which indicated that a
      tumor necrosis factor receptor fragment (TNF-RF) inhibits warm Tamb-induced sleep
      but not Tbr responses. Thus, brain IL-1 and TNF sleep and thermo mechanisms are,
      in part, different.

PMID- 9593506
TI  - Meningeal cells stimulate neuronal migration and the formation of radial glial
      fascicles from the cerebellar external granular layer.
AB  - The cerebellar granule cell layer and partly the Bergmann glial scaffold arise
      from a secondary subpial proliferative zone, the external granular layer. Their
      development can be disrupted by selective destruction of meningeal cells. In
      order to clarify the mechanisms of meningeal control of cortical development, we
      have investigated the development of early postnatal rat cerebellar slice
      explants in different coculture set-ups with meningeal cells and other
      fibroblasts. Fibroblasts of various sources (1) stimulate migration of
      undifferentiated neurons from the explants by a diffusible factor and (2) trigger
      the development of a radial phenotype in glial cells by contact-mediated
      mechanisms involving basal lamina constituents. These data provide further
      evidence for the involvement of mesenchymal-epithelial interactions in the
      development of the cerebellar cortex.

PMID- 9593507
TI  - Arachidonic acid potentiates the duration of the metabotropic, protein kinase C
      mediated, suppression of the inhibitory adenosine A1 receptor pathway in
      glutamatergic nerve terminals from rat cerebral cortex.
AB  - The KCl-evoked exocytotic release of glutamate from rat cerebrocortical
      synaptosomes is inhibited by a presynaptic adenosine A1 receptor decreasing
      voltage-activated Ca2+ entry. This inhibition was transiently suppressed by
      (1S,3R)-1-aminocyclopenthyl-1,3-dicarboxylate (ACPD) but was restored within 1
      min in the continued presence of the metabotropic agonist. In the presence of 2
      microM arachidonic acid ACPD initiated a prolonged suppression of the adenosine
      mediated inhibition persisting for at least 10 min. Arachidonic acid (20-40 pmol)
      was bound per mg synaptosomal protein. Prolonged ACPD-mediated phosphorylation of
      the protein kinase C (PKC) substrate myristoylated alanine-rich C-kinase
      substrate (MARCKS) was detected in the presence but not the absence of
      arachidonic acid, but arachidonic acid added 2 min after ACPD was ineffective. It
      is concluded that arachidonic acid synergistically prolongs the metabotropic
      glutamate receptor-mediated activation of presynaptic PKC, suppressing inhibitory
      receptor pathways.

PMID- 9593508
TI  - Urethral pudendal afferent-evoked bladder and sphincter reflexes in decerebrate
      and acute spinal cats.
AB  - Electrical stimulation of the urethral sensory pudendal nerve in decerebrate or
      acute spinal cats was used to evoke micturition reflexes in animals that failed
      to respond to bladder distension. In the decerebrate animals, stimulation of
      urethral afferents evoked voiding characterized by a large bladder pressure
      increase coordinated with a simultaneous decrease in external urethral sphincter
      activity. In animals in which the spinal cord was transected between T10 and L6,
      electrical stimulation of the urethral afferents evoked small increases in
      bladder pressure that were insufficient to expel fluid but the contractions were
      coordinated with a decrease in external urethral sphincter activity. It was
      concluded that in addition to interacting with spinobulbospinal micturition
      pathways, urethral pudendal afferents may have direct access to a spinal
      circuitry that can coordinate bladder and sphincter activity.

PMID- 9593509
TI  - Release of nociceptin-like substances from the rat spinal cord dorsal horn.
AB  - Release of nociceptin-like substances from the dorsal horn of rat spinal cords in
      situ was measured by the immobilized-antibody microprobe technique. Spinal cords
      removed from anesthetized 4-6 week-old rats were superfused with oxygenated Krebs
      solution at room temperature (21+/-1 degrees C). Glass microelectrodes, coated
      with antibodies to nociceptin, were inserted into the dorsal horn of the lumbar
      spinal cord (1.9 mm lateral to the midline to a depth 2.5 mm below the surface of
      the cord) for 15 min periods before, during and after electrical stimulation
      applied to the dorsal root entry zone of the same segment. There was a basal
      release of immunoreactive nociceptin-like substance (irNC) from the dorsal horns
      during the pre-stimulation period. A significant increase in irNC release was
      detected during the period of electrical stimulation and this increase was
      maintained for at least 15 min following the cessation of electrical stimulation.
      These results provide the first evidence on the release of irNC, albeit non
      quantitative, from the in situ rat spinal cord dorsal horn and an enhanced
      release upon electrical stimulation.

PMID- 9593511
TI  - Laminin-dependent integrin clustering with tyrosine-phosphorylated molecules in a
      Drosophila neuronal cell line.
AB  - To gain more insight into the molecular and cellular aspects of basement
      membranes during Drosophila morphogenesis, especially in neural development, we
      carried out cell biological screening to establish a cell culture system in which
      Drosophila cell-matrix interaction could be reconstituted. The screening showed
      that a Drosophila neuronal cell line, BG2-c6, established from the third-instar
      larval central nervous system, had a strong adhesion activity when purified
      Drosophila laminin was used as a substrate. Outgrowth of axon-like structures was
      stimulated on laminin. Histochemical analysis revealed clusters of integrin
      together with phosphotyrosine and alpha-actinin. These data indicate that the
      Drosophila integrin cascade triggered by the interaction between BG2-c6 and
      laminin was initiated at the integrin cluster with tyrosine-phosphorylated
      proteins, similar to the observations in vertebrate cells.

PMID- 9593510
TI  - Human supplementary motor area is active in preparation for both voluntary muscle
      relaxation and contraction: subdural recording of Bereitschaftspotential.
AB  - Bereitschaftspotentials (BPs) preceding muscle relaxation and contraction were
      compared by using subdural electrodes which were implanted onto the right medial
      frontal surface in two patients with supplementary motor area (SMA) seizure. The
      applied movement paradigm (muscle relaxation and contraction tasks) was
      completely the same as employed in our previous study [Terada, K., Ikeda, A.,
      Nagamine, T. and Shibasaki, H., Electroenceph. clin. Neurophysiol., 95 (1995) 335
      345]. In both patients, either negative or positive BPs were observed in the SMA
      proper and supplementary negative motor area (SNMA) starting at 1.2-1.8 prior to
      both movements. In one patient, BP was more widespread in the relaxation task
      whereas more restricted to the hand area in the contraction task. In the other
      patient, the BPs were observed in the cortical area rostral to SNMA (pre-SMA), in
      addition to the SMA-proper, in both tasks. It is concluded that SMA-proper and
      SNMA, and probably pre-SMA as well, in humans are similarly active in preparation
      for both voluntary muscle contraction and relaxation.

PMID- 9593512
TI  - Aberrant muscle activation in patients after resection of non-primary motor
      areas: demonstration by surface electromyography.
AB  - Two patients presented with a tumor involving mainly the supplementary motor area
      or the premotor cortex. Shortly after tumor resection, each developed transient
      impairment of voluntary movements. An electromyogram, with the skin electrodes
      placed over the muscles of the upper arms and forearms, demonstrated aberrant
      ipsilateral, contralateral or bilateral muscle activation during unilateral motor
      tasks in both patients. The bilateral activation was more prominent in the
      patient who had an intact dominant hemisphere. The present study suggests for the
      first time the importance of non-primary motor areas of the human brain in
      activating the proper set of muscles on the proper side of the body.

PMID- 9593513
TI  - Influence of docosahexaenoic acid on cerebral lipid peroxide level in aged rats
      with and without hypercholesterolemia.
AB  - Female Wistar rats, 100 weeks old, were divided into four groups: one group was
      fed a high-cholesterol diet, one received a non-cholesterol diet, and the others
      were fed either a non- or a high-cholesterol diet plus docosahexaenoic acid. The
      level of lipid peroxide (LPO) in brain tissue was measured with a LPO assay kit.
      Fatty acid concentrations were analyzed by gas chromatography. Brain LPO in the
      aged and hypercholesterolemic rats fed docosahexaenoic acid decreased in the
      cerebrum but not in the brain stem or cerebellum. In the cerebrum, LPO showed a
      decrease, with an increase in the ratio of docosahexaenoic acid to arachidonic
      acid. The cerebrum, unlike the other areas of the brain, was more sensitive to
      docosahexaenoic acid as the concentrations of LPO decreased.

PMID- 9593514
TI  - Inhibitory effects of bulbocapnine on dopamine biosynthesis in PC12 cells.
AB  - The effects of bulbocapnine, an aporphine isoquinoline alkaloid, on dopamine
      biosynthesis in PC12 cells were investigated. Bulbocapnine showed 45.2%
      inhibition on dopamine content in PC12 cells at a concentration of 20 microM for
      12 h. The IC50 value of bulbocapnine was 26.7 microM. Bulbocapnine at
      concentrations up to 80 microM was not cytotoxic towards PC12 cells. Tyrosine
      hydroxylase (TH) activity was inhibited by the treatment of bulbocapnine in PC12
      cells (24.4% inhibition at 20 microM). Bulbocapnine at 20 microM also decreased
      the intracellular Ca2+ concentration by 12.9% inhibition relative to control in
      PC12 cells. However, TH mRNA level was not altered by bulbocapnine treatment.
      These results suggest that the inhibition of TH activity by bulbocapnine might be
      involved in at least one component of the reduction of dopamine biosynthesis in
      PC12 cells.

PMID- 9593515
TI  - Identification of alternative splicing forms of GLT-1 mRNA in the spinal cord of
      amyotrophic lateral sclerosis patients.
AB  - The glutamate transporter plays an essential role in regulating glutamate levels
      in the synaptic cleft. It has been postulated that the dysfunction of GLT-1, one
      subtype of glutamate transporter, may be etiologically related to amyotrophic
      lateral sclerosis (ALS). Two alternative splicing forms of GLT-1 messenger RNA
      (mRNA) were found in the cervical spinal cord of five ALS patients and three
      controls. Analysis with reverse transcription-polymerase chain reaction (RT-PCR)
      showed that the shorter mRNA was a result of exon 8 skipping. A truncated
      transcript containing an intronic sequence at the 3' end of exon 7 was also
      demonstrated. However, the incidence of both alternative mRNAs was not different
      between the five ALS patients and three controls. Interestingly, the mRNA were
      also found in the cerebral cortex of a control subject. These results suggest
      that alternative splicing forms of GLT-1 mRNAs do not play a pathogenetic role in
      ALS but rather a physiological one in the normal spinal cord and brain.

PMID- 9593516
TI  - Serial changes of sensory nerve conduction velocity and minimal F-wave latency in
      streptozotocin-induced diabetic rats.
AB  - We studied the serial changes of sensory nerve conduction velocity (SNCV) in the
      caudal nerve of streptozotocin (STZ)-induced diabetic rats using a new technical
      method. Minimal F-wave latency was also studied by stimulating the tibial nerve.
      The SNCV in the diabetic rats was slower than that in the normal rats 2 weeks
      after STZ injection, and minimal F-wave latency was prolonged compared to normal
      rats 4 weeks after STZ injection. Treatment of the diabetic rats with insulin for
      14 days inhibited SNCV slowing and minimal F-wave latency prolongation. This new
      method to measure SNCV is useful for various studies, and improvement of diabetic
      neuropathy with insulin treatment is indicated by recovery from SNCV slowing and
      minimal F-wave latency prolongation.

PMID- 9593517
TI  - Cataloging altered gene expression during rat hippocampal long-term potentiation
      by means of differential display.
AB  - We have employed mRNA differential display (DD) to generate a catalog of cDNAs
      whose expression in the hippocampus was regulated during long-term potentiation
      (LTP) in dentate gyrus of anesthetized rats. DD with 459 combinations of primer
      pairs revealed that 80 out of approximately 70000 bands displayed showed a
      reproducible change in their expression level. These cDNAs were categorized into
      seven groups according to changes in their temporal expression pattern. Some of
      these cDNAs were induced rapidly, but transiently, after the LTP induction, some
      induced rapidly and persistently, some induced slowly, and some down-regulated
      following LTP. This suggests that a complex molecular hierarchy underlies the
      maintenance of hippocampal LTP.

PMID- 9593518
TI  - Protein extracts from the gut wall influence the postnatal development of rat
      myenteric neurons in vitro.
AB  - Neurons migrating from the neural crest into the presumptive gut wall need an
      appropriate microenvironment to survive and differentiate during ontogenesis. The
      rat enteric nervous system (ENS) keeps developing beyond birth. The aim of this
      study was to investigate the neurotrophic effects of the postnatal
      microenvironment. Myenteric plexus was isolated from the smooth muscle layer of
      newborn rats at different ages (postnatal day (p)1, p7, p14) and grown as
      dissociated cell cultures. The culture medium (hormone-supplemented, serum-free)
      was supplemented either with glial-cell-line-derived-neurotrophic factor (GDNF)
      or with protein extracts from homogenized smooth muscle layer of p7 rats.
      Cultures kept in defined medium alone were used as controls. After 18 h in vitro
      both GDNF and protein extract had a neuritogenic effect upon p1 and p7 neurons,
      while p14 neurons were only stimulated by the protein extracts. The GDNF effect
      upon these neurons did not differ significantly from the effects in defined
      medium alone. The average neurite outgrowth in extract-supplemented cultures was
      always longer than that seen in those treated with GDNF. Although GDNF influences
      the postnatal development of myentric neurons in vitro it could not be detected
      immunohistochemically either in Western blots of the protein extracts or in
      cryostat sections of the gut.

PMID- 9593519
TI  - Follicular dynamics in Mangalarga mares.
AB  - Ovarian follicular activity was studied by ultrasonography during 17 oestrous
      cycles in 9 Mangalarga mares during the second half of the ovulatory season.
      Sixteen oestrous cycles were considered normal and one 3-wave cycle showing a
      prolonged luteal phase was considered atypical. Daily ultrasonographic
      examinations were performed and the compiled data on follicular dynamics were
      studied retrospectively. One major wave of follicular growth was observed in 13
      of the 16 normal cycles (81.25%), whereas 2 major waves occurred in 3 cycles
      (18.75%). The mean (+/- s.d.) days of emergence of the primary wave of follicular
      development in cycles containing one or 2 waves were Day 6.0 +/- 2.3 and Day 11.0
      +/- 1.0, respectively. The secondary wave of follicular development in 2-wave
      cycles emerged on Day 0.0 +/- 3.6. The day of wave divergence for primary waves
      of follicular development in cycles which exhibited one or 2 major waves were Day
      12.2 +/- 3.5 and Day 17.3 +/- 3.0, respectively. Divergence of secondary waves
      occurred in only one of the 3 cycles which exhibited 2 major follicular waves
      (Day 7). The mean (+/- s.d.) maximum diameters of the dominant follicle in the
      primary wave of oestrous cycles exhibiting one and 2 major waves were 39.0 +/-
      3.9 mm and 34.7 +/- 2.5 mm, respectively. The mean (+/- s.d.) maximum diameter of
      the dominant follicle present in the secondary wave was 34.3 +/- 11.0 mm. The
      mean (+/- s.d.) lengths of the interovulatory intervals for cycles containing one
      and 2 major waves were 19.4 +/- 2.2 and 23.3 +/- 2.5 days, respectively. These
      data indicate that most Mangalarga mares show one major follicular wave during
      the oestrous cycle but a small percentage of mares show 2 major waves.

PMID- 9593520
TI  - A comparison of the biochemical composition of equine follicular fluid and serum
      at four different stages of the follicular cycle.
AB  - Samples of blood and follicular fluid were recovered from 27 Welsh Pony mares at
      4 distinct stages of follicular development. Eighteen biochemical parameters were
      measured in each sample, including sodium, potassium, chloride, glucose, urea,
      creatinine, calcium, inorganic phosphate, total bilirubin, total protein,
      albumin, magnesium, triglyceride, total cholesterol, nonesterified fatty acids,
      alkaline phosphatase, gamma-glutamyltransferase and aspartate aminotransferase.
      The concentrations of progesterone, 17beta oestradiol and testosterone, pH and
      osmolarity, were also measured in all the follicular fluid samples. The
      concentrations of all proteins measured were lower in follicular fluid than serum
      whereas the reverse was true in the case of the lipids. Analysis of variance
      indicated that serum and follicular fluid concentrations of most of the
      parameters measured varied in parallel.

PMID- 9593521
TI  - Long term exposure to T-2 Fusarium mycotoxin fails to alter luteal function,
      follicular activity and embryo recovery in mares.
AB  - The effect of long term administration of T-2 toxin was studied in 6 Trotter
      mares during the summer and early autumn. After one complete oestrous cycle
      (Cycle 1) each mare was given 7 mg purified T-2 toxin per os daily (1 mg/ml in
      ethyl alcohol) beginning on Day 10 after ovulation in Cycle 2. Exposure to toxin
      was continued for 32-40 days, until Day 7 of Cycle 4. During this period all the
      animals remained in good physical condition, but skin lesions were observed
      around the mouth in 3 cases. Toxin administration had no effect on the length of
      the interovulatory interval or on the lengths of the luteal and follicular
      phases. It also had no effect on peripheral plasma progesterone profiles or
      follicular kinetics, including the growth rate and maximum size of ovulatory
      follicles and the maximum number, and time of first increase in number, of
      follicles larger than 1 and 2 cm. Uterine flushing was attempted in 5 mares and
      yielded 3 embryos (60%). These were of normal size and morphology and one was
      transferred nonsurgically to a recipient mare; a conceptus developed initially
      but it subsequently died and was resorbed. The results of the study allowed the
      conclusion that the administration of 7 mg/day T-2 toxin to mares in good body
      condition has no detrimental effect on ovarian activity, fertilisation or
      oviductal transport.

PMID- 9593523
TI  - Effects of follicular aspiration and flushing, and the genotype of the fetus on
      circulating progesterone levels during pregnancy in the mare.
AB  - When aspirating ovarian follicles in pregnant mares to obtain oocytes for in
      vitro fertilisation (IVF), the effect of the manipulation on circulating
      concentrations of progesterone may be an important consideration in terms of the
      maintenance of pregnancy. The object of this study was to compare the effects of
      3 different forms of transvaginal ultrasound-guided follicle aspiration
      (Treatment 1, no aspiration, n = 4; Treatment 2, aspirate only follicles > or =20
      mm in diameter, n = 7; Treatment 3, aspirate all visible follicles, n = 7) on
      peripheral plasma progesterone concentrations between Days 21 and 150 of
      gestation in 9 mares carrying intraspecies horse and 9 mares carrying
      interspecies mule conceptuses. The 3 follicle aspiration treatments were applied
      at the peak of each follicular wave as determined by follicular mapping by means
      of transrectal ultrasonography on alternate days. The plasma progesterone profile
      in mares undergoing Treatment 1 was in close agreement with those reported
      previously in pregnant mares. A decline in plasma progesterone levels occurred
      after Day 53 of gestation in Treatments 2 and 3 mares, indicating that the
      follicular aspiration procedures did interfere with the formation of secondary
      corpora lutea. However, the levels in individual mares never dropped low enough
      to endanger the pregnancy. Mares carrying mule pregnancies exhibited higher mean
      plasma progesterone concentrations between Days 39 and 45 of gestation than mares
      carrying horse pregnancies, equivalent levels between Days 46 and 66 despite the
      lower circulating concentrations of chorionic gonadotrophin (mule CG) in their
      blood during this period and lower progesterone levels between Days 67 and 150 of
      gestation. The results indicate that the primary corpus luteum in the pregnant
      mare may be more sensitive to mule CG than horse CG. Furthermore, the earlier
      disappearance of CG from the circulation in mares carrying mule fetuses is
      reflected by an earlier decline in plasma progesterone concentrations in this
      type of equine pregnancy.

PMID- 9593524
TI  - Timing of in vivo maturation of equine preovulatory oocytes and competence for in
      vitro maturation of immature oocytes collected simultaneously.
AB  - The objects of this study were to monitor the development of the cumulus complex
      and nuclear maturation in oocytes recovered from preovulatory follicles following
      treatment to induce ovulation and to investigate the in vitro maturation
      competence of oocytes recovered from smaller nonpreovulatory follicles of varying
      size. All follicles > or =5 mm in pony mares were individually punctured at 0, 6,
      12, 24 and 35 h after an injection of LH to induce ovulation. The recovery rates
      of oocytes were 64% from 55 preovulatory follicles, 22% from 32 subordinate
      follicles and 52% from 227 small follicles. Cumulus expansion of the preovulatory
      oocytes occurred at 12 h post LH treatment while the metaphase I and II
      components of nuclear maturation were not completed until 24 and 35 h post LH
      respectively. For nonpreovulatory follicles, the frequency of atresia and oocyte
      competence for in vitro nuclear maturation both increased with increasing
      follicular size.

PMID- 9593522
TI  - Follicular fluid is not a compulsory carrier of the oocyte at ovulation in the
      mare.
AB  - The aim of this study was to test the possibility that ovulation can occur from a
      preovulatory follicle emptied of its follicular fluid. Transport of the oocyte
      into the oviduct and fertilisation in 29% of cases demonstrated that ovulation
      can occur in the absence of follicular fluid but the higher fertility achieved in
      control mares (62.5%) suggested that follicular fluid does serve a role during
      ovulation, fertilisation and oviductal transport. Injection of horse oocytes into
      preovulatory follicles in mules after removal of the follicular fluid, followed
      by insemination of the mules with horse semen, resulted in the production of one
      horse x horse embryo.

PMID- 9593525
TI  - Equine oocyte-cumulus morphology as affected by follicular size.
AB  - From the ovaries of 256 slaughtered mares a total of 1713 follicles were isolated
      from which 1641 (95.8%) oocytes were recovered (6.4/mare). A total of 564
      follicles and oocytes were evaluated for the degree of vascularisation of the
      follicle wall, the appearance of the follicular fluid and the location and
      morphology of the cumulus-oocyte-complex. Follicles with a diameter of >10 mm
      displayed more numerous, well branched and more pronounced blood vessels than the
      smaller ones (4-10 mm diameter) and most of them contained clear, yellowish fluid
      with few granulosa cells. The percentage of oocytes with compact cumuli increased
      significantly with an increasing diameter of the follicle, being 233%, 43.9%,
      55.6% and 64.2% (P<0.01) for the follicles with diameters of 4-10, 11-15, 16-20
      and 21-35 mm, respectively. The percentage of oocytes attached to the follicle
      wall also increased with increasing follicle size, being 48.0%, 59.6%, 81.5% and
      90.1% (P<0.01), respectively. On the contrary, the percentage of oocytes floating
      in the follicular fluid decreased with increasing follicle diameter, from 52.0%
      in the smallest follicles to 9.9% in the biggest ones. A significantly greater
      percentage of oocytes found on the follicular wall than in the follicular fluid
      had a compact cumulus (56.6 versus 21.3%; P<0.01). For in vitro culture were
      accepted 30.4%, 54.3%, 60.7% and 77.8% (P<0.01) of oocytes from the follicles
      with diameters of 4-10, 11-15, 16-20 and 21-35 mm, respectively. After culture
      for 28-40 h in TCM 199 medium, 90 of a total of 165 (54.5%) oocytes reached the
      metaphase II stage of maturation.

PMID- 9593526
TI  - Cumulus expansion, chromatin configuration and meiotic competence in horse
      oocytes: a new hypothesis.
AB  - When recovered from the follicle, horse oocytes may be categorised as having
      either a compact or an expanded cumulus. Cumulus expansion is strongly associated
      with follicle atresia. Oocytes with expanded and compact cumuli have similar
      proportions in the germinal vesicle stage when recovered from the follicle.
      However, during in vitro culture, a higher proportion of oocytes with expanded
      cumuli mature, and they do so more quickly, than do oocytes with compact cumuli.
      Using Hoechst 33258 to label chromatin, in the germinal-vesicle stage horse
      oocytes can be divided into those in which the nucleus fluoresces diffusely (FN),
      and those in which the chromatin is condensed as a mass within the germinal
      vesicle (condensed chromatin; CC). The CC configuration is more common in oocytes
      with expanded rather than compact cumuli. The occurrence of the condensed
      chromatin configuration in oocytes with compact cumuli rises with increasing
      follicle size to the point that, in follicles >20 mm diameter, almost 80% of
      oocytes with compact cumuli have condensed chromatin. This suggests that the
      chromatin of fully grown oocytes condenses prior to the gonadotrophin stimulation
      that induces ovulation. The number of oocytes maturing in vitro correlates
      strongly with the presence of the condensed chromatin configuration at the
      beginning of culture for both cumulus types. This suggests that the condensed
      chromatin configuration represents the meiotically competent oocyte. In contrast,
      FN oocytes appear to be meiotically incompetent, although 61% of oocytes from
      small, apparently viable follicles, have the FN configuration. This leads to the
      hypothesis that the FN configuration represents viable germinal vesicle stage
      oocytes that have yet to acquire meiotic competence. As oocytes achieve meiotic
      competence, the chromatin appears to condense to the CC configuration. This
      change occurs during growth of the preovulatory follicle but it can also occur
      during follicular atresia. Information about the inherent meiotic competence of
      different populations of oocytes will assist in the selection of oocytes for
      experiments involving in vitro maturation and fertilisation in equids.

PMID- 9593527
TI  - Comparison of different methods for the recovery of horse oocytes.
AB  - The object of this study was to compare 4 different methods of oocyte recovery
      from mares; 1) transvaginal follicle aspiration in vivo; 2) follicle aspiration
      in vitro; 3) oocyte recovery by isolation of follicles in vitro and 4) follicle
      scraping in vitro. Oocyte recovery was highest after follicle scraping (71.1%)
      and follicle isolation and rupture (61.3%). Follicle aspiration in vitro and in
      vivo yielded oocytes on 31.2% and 19.3% of occasions, respectively. The output of
      different types of cumulus-oocyte-complexes was different among the methods; the
      portion of compact cumulus-oocyte-complexes was significantly higher with
      follicle scraping (50.7%) and follicle isolation (44.5%) than with aspiration in
      vivo (31.9%) and in vitro (23.7%). The recovery rate of oocytes from small
      follicles (<15 mm) was significantly higher than from larger follicles (P<0.05)
      using transvaginal follicle aspiration. The proportion of oocytes that were
      degenerate (exhibited shrunken, dense or visibly damaged ooplasm) ranged from
      1.2% after follicle scraping, to 17.2% after aspiration in vivo. These results
      indicate that, for the recovery of horse oocytes in vitro, follicle scraping and
      follicle isolation give the highest recoveries of cumulus-intact oocytes.

PMID- 9593528
TI  - Treatment of equine oocytes with A23187 after intracytoplasmic sperm injection.
AB  - In vitro matured horse oocytes with a first polar body (n = 68) were each
      injected with a single spermatozoon and divided into 2 groups: Group 1 oocytes
      were treated with 10 microM calcium ionophore A23187 for 5 min while Group 2
      oocytes received no activation treatment. After culture in vitro for 2 days,
      significantly more oocytes treated with A23187 (5/24, 21%) cleaved than oocytes
      without activation treatment (2/44, 5%, P<0.05). All 7 cleaved zygotes from both
      treatment groups were transferred to recipient mares but no pregnancies resulted.

PMID- 9593529
TI  - Transfer of immature oocytes to a preovulatory follicle: an alternative to in
      vitro maturation in the mare?
AB  - In the mare, success rates for the in vitro maturation of oocytes are low.
      Accordingly, we attempted to determine if immature oocytes could be matured in
      vivo by injecting them into a preovulatory follicle. Groups of 3-9 oocytes
      collected from donor mares were transferred under ultrasound control into the
      preovulatory follicle of a recipient mare that was treated with crude equine
      pituitary gonadotrophin (CEG) to induce ovulation. Just before ovulation (34 h
      post treatment) the preovulatory follicle of the recipient mare was punctured to
      collect both the transferred and the indigenous oocytes to analyse the stages of
      nuclear maturation. The transfer technique did not impair significantly the final
      maturation of the recipient preovulatory follicle. The indigenous oocytes within
      the recipient follicles were recognisable by their larger expanded cumulus of
      yellow colouration due to high hyaluronic acid content; 7/12 of these oocytes
      were mature (metaphase II). Around half (42/86; 49%) of the oocytes transferred
      to preovulatory follicles were recovered subsequently. Most of them showed
      cumulus expansion (41/42, 6 of which were rich in hyaluronic acid), 13 (32%) were
      mature, 15 (36%) were immature and 13 (32%) were degenerate. When the indigenous
      oocyte of the recipient mare was mature, 38% of the transferred oocytes were
      mature, this rate being no different from the in vitro maturation rate of 46%.
      This study showed that in vivo maturation of immature oocytes by transfer into a
      preovulatory follicle in a recipient mare is possible. The maturation rate is not
      different from the in vitro maturation rate. The technique allows the generation
      of mature oocytes that have an expanded cumulus rich in hyaluronic acid, similar
      to the situation in preovulatory oocytes. This result has not been obtained in
      vitro previously.

PMID- 9593530
TI  - Success rates when attempting to nonsurgically collect equine embryos at 144, 156
      or 168 hours after ovulation.
AB  - The purpose of this study was to evaluate the exact age when the equine embryo
      reaches the uterus. The time of ovulation was determined by hourly ultrasound
      examinations starting 32 h after an injection of crude equine pituitary
      gonadotrophin or human chorionic gonadotrophin, or after the first of 4
      injections of buserelin. Nonsurgical uterine flushings were carried out 144 h
      (Day 6), 156 h (Day 6.5) or 168 h (Day 7) after ovulation. Induction of ovulation
      was attempted in 101 oestrous cycles and 61 of 101 mares (60.4%) ovulated 32-44 h
      post injection. Sixty embryo collections were performed which yielded: 0/20
      embryos at 144 h, 9/17 embryos (53%) at 156 h and 12/23 embryos (52%) at 168 h.
      The mean (+/- s.e.m.) diameter of the embryo was significantly greater (P<0.01)
      at Day 7 (244 +/- 15 microm) than at Day 6.5 (186 +/- 9.1 microm), and
      variability in size was observed among embryos collected from the same mare after
      synchronous natural multiple ovulations. These results suggest that; i) horse
      embryos enter the uterus between 144 and 156 h after ovulation, and ii) the time
      interval between ovulation and fertilisation in mares is inconsistent and/or
      embryonic development rate may differ between individual embryos.

PMID- 9593531
TI  - Spontaneous multiple ovulation and development of multiple embryonic vesicles in
      a mare.
AB  - A Warmblood mare was observed to ovulate spontaneously 12 follicles within 2
      days, none of which exceeded 22 mm in diameter. On Days 13 and 17 after
      ovulation, 6 embryonic vesicles were identified in the uterus by ultrasonography
      but by Day 26, 5 of the vesicles had disappeared. Development of the surviving
      conceptus was monitored until Day 42. Plasma progesterone concentrations rose to
      14 ng/ml on Day 7, decreased over the next 8 days and then plateaued to around 4
      6 ng/ml until Day 70. The occurrence of multiple spontaneous ovulations was
      diagnosed repeatedly in this mare. However, the developmental competence of the
      ovulated oocytes seemed to be impaired.

PMID- 9593532
TI  - Parentage testing of Day 10 equine embryos by amplified PCR analysis of
      microsatellites.
AB  - Paternity analysis was performed on the DNA of 21 equine embryos collected
      nonsurgically 10 days after ovulation from known mares, but involving 3 possible
      sires. After extraction, the DNA of each embryo was typed by radioactive PCR
      amplification using 10 characterised microsatellites; HMS 1, 2, 5, 6, 7 and 8
      (Guerin et al. 1994) and HTG 3, 4, 6 and 10 (Marklund et al. 1994). The 21 dams
      and 3 sires were genotyped using DNA extracted from blood and amplified by PCR.
      After electrophoresis and autoradiography of the PCR products of the embryo and
      parents, the alleles of the embryo were compared to those of the dam to identify
      those of maternal origin. The paternal alleles were then searched for within the
      genotype of the 3 sires, and the stallion(s) that exhibited the particular allele
      was said to be compatible with the embryo for this microsatellite. In this way,
      the true sire was identified correctly for all 21 embryos.

PMID- 9593533
TI  - Distribution of putative primordial germ cells in equine embryos.
AB  - Eighteen equine embryos, 3 each on Days 20, 22, 24, 26, 28 and 30 post ovulation,
      were collected transcervically by uterine lavage, fixed in 4% paraformaldehyde
      and embedded in paraffin wax. Ten micron serial sections were stained to
      determine alkaline phosphatase (AP) activity in the cells. Positive cells were
      counted and their approximate location determined. The cells were approximately 8
      microm in diameter and the entire cell, except the nucleus, stained strongly with
      many small round areas of intense staining in the cytoplasm. The cells varied
      from round to elongated in shape and pseudopodia were often present. Thus, they
      were similar in shape and staining pattern to primordial germ cells described in
      other species. A total of 2 AP-positive cells were found in the 3 Day 20 embryos
      and the mean number of AP-positive cells changed (P<0.05) over the succeeding
      days as follows; Day 20 = 1; Day 22 = 251; Day 24 = 1484; Day 26 = 2385; Day 28 =
      3267; Day 30 = 2424. AP-positive cells present in the liver were not included in
      the calculations. In the Day 22 embryos, 10% of the putative primordial germ
      cells were found within the vascular system, including the heart chambers, and
      only 4% were found along the genital ridge. The percentage of cells found in the
      vascular system decreased from 10% on Day 22 to 1% on Day 30, although not
      significantly. The percentage of cells found along the genital ridge changed
      (P<0.05) over gestational age as follows; Day 22 = 4%; Day 24 = 10%; Day 26 =
      28%; Day 28 = 28%; Day 30 = 16%. Once the putative primordial germ cells reached
      the developing gonads they were no longer AP-positive and nor was the gonadal
      stroma. The rest of the cells were distributed along the dorsal mesentery (range,
      14-24%), near the dorsal aorta (16-29%), in the mesonephros (1-3%) and in other
      areas of the embryo (27-44%). Large numbers were in the cranial portion of the
      embryo. Although it is likely that the population of AP-positive cells counted
      included the primordial germ cells, other cells, such as haematopoietic precursor
      cells, could not be ruled out. The AP reactivity, the appearance of the cells and
      their migratory pattern through the dorsal mesentery to the gonadal ridge were
      consistent with descriptions of primordial germ cells in other species. Their
      distribution throughout the embryo, especially its cranial aspect and their
      location within, or in close proximity to, blood vessels suggested that the
      equine embryo is unusual among mammals in that some of its primordial germ cells
      migrate through the blood.

PMID- 9593534
TI  - The use of early pregnant mares as embryo recipients.
AB  - Fourteen normal, cyclic mares, treated to synchronise oestrus and ovulation and
      inseminated artificially with fresh semen, were assigned to a donor or a
      recipient group after ovulation, with the aim of obtaining a degree of synchrony
      of > or =2 days. Ten embryos, collected on Day 6 or 7 after ovulation (Day 0),
      were transferred nonsurgically to inseminated recipient mares (IRM) that had
      ovulated up to 5 days after the respective donors, or to pregnant recipient mares
      (PRM) that had ovulated 2-7 days before the donors. Embryonic size and
      development, as determined by ultrasound examination, were used to distinguish
      embryos derived from the recipient (recipient embryo = RE) or from the donor
      (transferred embryo = TE) mare. In cases of twin pregnancy, the RE was manually
      squeezed on Days 14-16. Abortion was induced in all mares on Day 30. Three of 6
      TE developed in IRM. Two of 6 IRM developed a twin pregnancy (RE+TE), while 4 of
      6 IRM developed a singleton pregnancy (1 TE and 3 RE). None of 4 TE developed in
      Day 9-14 PRM and one of these PRM lost her own embryo following ET. The
      experiment demonstrated that a mare can carry her own embryo and a transferred
      embryo simultaneously. However, the status of pregnancy does not improve
      conception rate in recipient mares that ovulate prior to the donor.

PMID- 9593535
TI  - The effect of propanediol on the morphology of fresh and frozen equine embryos.
AB  - Seventeen horse embryos recovered on the sixth day after spontaneous ovulation
      were; 1) washed in PBS (n = 6), 2) treated with 1.5 M 1-2 propanediol (n = 6) or,
      3) frozen and thawed using 1.5 M propanediol as the cryoprotectant (n = 5). After
      treatment, the embryos were incubated for 6 h in medium before they were fixed,
      serially sectioned and examined microscopically to count the total numbers of
      interphase, mitotic and pycnotic nuclei. Significant differences were measured
      only in the mean proportions of pycnotic cells (+/- s.d.), both between the
      control (9.2 +/- 7.3%) and frozen-thawed embryos (52.8 +/- 37.1%; P<0.05) and
      between the propanediol-treated (10.8 +/- 4.6%) and the frozen-thawed embryos
      (P<0.01). Propanediol appears to be minimally toxic to equine embryos but it is a
      poor cryoprotectant.

PMID- 9593536
TI  - Effect of anti-freeze protein (AFP) on the cooling and freezing of equine embryos
      as measured by DAPI-staining.
AB  - Equine embryos recovered on Day 6 after ovulation were cooled to +4 degrees C, or
      frozen with AFP alone or together with glycerol. Twenty embryos (140-200 microm
      in diameter) were randomly assigned to 6 treatment groups. In the first 3 groups,
      the embryos were cooled from room temperature to +4 degrees C at a rate of 3
      degrees C/min and warmed again at a rate of 32 degrees C/min in a programmable
      freezer. In the second 3 groups, the embryos were frozen using a standard
      protocol, stored in liquid nitrogen for 5-7 days and then thawed in a 37 degrees
      C waterbath. After cooling/warming or freezing/thawing all the embryos were
      stained with DAPI. The percentage of dead cell area was significantly lower in
      the cooling groups than in the freezing groups and no significant differences
      were apparent between the cryoprotectants used in the study.

PMID- 9593537
TI  - Cryopreservation of equine embryos with glycerol plus sucrose and glycerol plus
      1,2-propanediol.
AB  - Six or 7-day-old equine embryos were divided into 4 groups; Group 1, n = 15, Day
      7 embryos destined for immediate transfer; Group 2, n = 15, Day 6 embryos
      destined for deep-freezing with glycerol plus sucrose as cryoprotectant; Group 3,
      n = 10, Day 6 embryos destined for deep-freezing with glycerol plus 1,2
      propanediol as cryoprotectant and Group 4, n = 3, fresh embryos destined for
      ultrastructural analysis. All the frozen/thawed embryos were transferred to
      recipient mares, except 3 embryos in Group 3 that were subjected to
      ultrastructural analysis. After thawing the cryoprotectants were removed by
      successive dilutions in PBS + 15% v:v fetal calf serum (FCS) containing
      decreasing concentrations of the cryoprotectants. Pregnancy was diagnosed
      ultrasonographically in 53.3%, 13.3% and 0% of the mares in Groups 1, 2 and 3
      respectively. Ultrastructural analysis showed differences between frozen/thawed
      and fresh embryos. In the former, embryonic cells were deformed and showed
      dilation of the intercellular and perivitelline spaces, a decrease of desmosome
      number in the junctional complexes, few microvilli on the apical surface of the
      trophectoderm and an almost total absence of pinocytotic vesicles. Most of the
      mitochondria showed regions containing dilation and irregularities on the
      cristae, which appeared electron-dense. The results obtained with Groups 2 and 3
      embryos showed that the cryoprotectants employed were not effective in protecting
      the embryos against damage during freezing and thawing. Indeed, the
      ultrastructural changes observed in the Group 3 embryos explained the absence of
      any established pregnancies in this group of mares.

PMID- 9593538
TI  - The effect of sucrose in the thawing solution on the morphology and mobility of
      frozen equine embryos.
AB  - Seventy-five embryos were collected 6 days after ovulation. Sixty embryos were
      frozen in straws using glycerol as the cryoprotectant in an automatic freezer. In
      Experiment 1 the freezing and thawing media were supplemented with 1.3 g/l PVP;
      in Experiment 2 the supplement was 5% FCS. The embryos were thawed for 30 s at
      +37 degrees C in a waterbath. In Experiment 1 glycerol was removed from 10
      embryos in 6 steps. In 10 other embryos, glycerol and sucrose were both removed
      from the medium in 6 steps. After glycerol and sucrose removal, the embryos were
      stained with 4',6'-diamidino-2-phenylindole (DAPI) to count the percentage of
      dead cells. Fluorescent rate (FR) was defined as a ratio of fluorescent area
      versus total area. Mean (+/- s.d.) FR in this experiment was significantly lower
      (P<0.01) in embryos thawed with sucrose (0.28 +/- 0.13) than in embryos thawed
      with glycerol alone (0.53 +/- 0.25). In Experiment 2, 40 embryos were frozen and
      glycerol, with or without sucrose, was removed after thawing as for Experiment 1.
      Ten embryos in both groups were stained with DAPI. All the frozen-thawed embryos
      were transferred nonsurgically to recipient mares. Fourteen fresh embryos were
      transferred as controls, 7 of which were stained with DAPI before transfer. There
      was no difference in pregnancy rates between DAPI-stained versus nonstained
      embryos, indicating that the staining process had no negative effects on
      embryonic survival. Insufficient embryos were transferred to be able to
      demonstrate any difference in pregnancy rates between embryos thawed with or
      without sucrose in the medium.

PMID- 9593539
TI  - Cryopreservation procedures for Day 7-8 equine embryos.
AB  - Larger grade 1 or 2 (1 = excellent,.... 4 = degenerate) equine embryos that
      ranged in diameter from 300 to 680 microm and were recovered from mares on Day 7
      or 8 after ovulation, were randomly assigned to 3 widely divergent
      cryopreservation treatments. Treatment 1 consisted of cooling from -6 degrees C
      to -35 degrees C at 0.5 degrees C per min followed by plunging into liquid
      nitrogen, with a one-step addition and a 4-step removal of 1.0 M glycerol.
      Treatment 2 (step-down equilibration) consisted of a 2-step addition of glycerol
      to 4.0 M followed by a decrease to 2.0 M prior to freezing, with galactose
      present in the final step and in all glycerol removal steps and with a cooling
      protocol identical to Treatment 1. Treatment 3 was a standard vitrification
      protocol with step-wise addition of ethylene glycol up to 11.9 M, and step-wise
      removal of cryoprotectant with decreasing concentrations of galactose in the
      dilution medium. The cryoprotectants were removed at 20-21 degrees C. After the
      final dilution, the embryos were cultured in 5% CO2-in-air for 36 h at 38.5
      degrees C on equine oviductal epithelial cell monolayers. Their morphology was
      then evaluated, their capsules were removed mechanically, and they were fixed
      prior to staining with 1% w:v orcein in 45% acetic acid to assess the morphology
      of their nuclei and cytoplasm. All 7 embryos in Treatment 1 degenerated during
      thawing or culture. Of the 6 embryos included in Treatment 2, 4 were graded 1,
      one was graded 2 and one graded 3 after culture in vitro. Of the 7 embryos in
      Treatment 3, one was graded 2, one was graded 3 and the remaining 5 were
      degenerate (P<0.01 among treatments). The average changes in initial diameter
      exhibited by the frozen/thawed embryos during culture after thawing were:
      Treatment 1, -91 microm; Treatment 2, +179 microm; Treatment 3, +20 microm
      (P<0.05). Two 26-day pregnancies were established following transfer of 6
      Treatment 2 embryos (step-down equilibration method) to recipient mares.

PMID- 9593540
TI  - Living fibroblast cells in the oviductal masses of mares.
AB  - The object of this experiment was to estimate the number and type of living cells
      in oviductal masses of mares. Oviducts of abattoir mares were dissected, divided
      into 3 sections, and flushed individually. Oviductal masses were recovered from
      220 of 250 mares and from 389 of 500 oviducts. A greater number of masses was
      recovered from the left than the right oviducts. A higher percentage of masses
      was recovered from the ampullary-isthmic junction than from the ampulla or
      isthmus. The number of masses increased slightly with increasing mare age and was
      weakly correlated with the number of unfertilised oocytes recovered per oviduct.
      Prepubertal mares had fewer recovered masses than anovulatory, early luteal
      phase, late luteal phase, or pregnant mares. Oviductal masses were classified
      morphologically as being branched, compact, or cumulus. Living cells were
      identified with a carboxy fluorescein diacetate stain and dead cells were
      identified with a propidium iodide fluorescent stain. In branched masses, the
      proportion of the surface area covered with total cells (live and dead) was 33.7
      +/- 14.3%, and with only live cells was 6.2 +/- 7.3%. In compact masses, the
      proportion of the surface area covered with total cells was 42.4 +/- 21.2%, and
      with only live cells was 10.7 +/- 13.1%. The detection of living cells was
      confirmed by isolating and culturing cells. Cells cultured from cumulus masses
      were viable in 57.1% of wells, whereas cells from branched and compact masses
      were viable in only 18.1% and 17.7% of wells, respectively. In addition, more of
      the surface area of wells containing cells from cumulus masses were covered with
      cells, compared to wells containing cells from either branched or compact masses.
      Most cells appeared to be fibroblasts because 90-95% of cells from branched and
      compact masses were stained with a fibroblast cell marker.

PMID- 9593541
TI  - Endometritis, salpingitis and fertilisation rates after mating mares with a
      history of intrauterine lumenal fluid accumulation.
AB  - The occurrence of uterine and oviductal inflammation, and fertilisation rates,
      were measured on Day 3 post ovulation in inseminated mares that had either
      exhibited intrauterine lumenal fluid during a previous dioestrus (Experiment 1)
      or had acute endometritis induced by intrauterine infusion of 1% glycogen
      (Experiment 2). Endometritis was assessed by uterine cytology and histology
      whereas oviductal inflammation was measured histologically. Fertilisation rates
      were calculated from the percentage of cleaved ova recovered by retrograde
      flushing of the oviducts. Mares with or without pre-existing uterine fluid during
      dioestrus that were inseminated showed a higher incidence of endometritis than
      control mares without pre-existing uterine fluid that were not inseminated (n = 7
      mares/group). However, inseminated mares with uterine fluid did not show a higher
      incidence of endometritis than inseminated mares without uterine fluid. Mares
      with or without pre-existing uterine fluid showed a higher incidence of
      endometritis than salpingitis and these 2 groups of mares showed equivalent rates
      of fertilisation and oviductal oocyte recovery. Mares inseminated with semen
      alone or semen following 1% glycogen treatment had a higher incidence of
      endometritis than control noninseminated mares (n = 17 mares/group) but mares
      that received semen plus 1% glycogen did not show a higher incidence of
      endometritis than mares that received semen alone. Both these groups of mares
      showed a higher incidence of endometritis than salpingitis and those that
      received semen plus 1% glycogen showed an equal recovery rate of recently
      ovulated ova but a lower fertilisation rate than the mares that received semen
      alone.

PMID- 9593542
TI  - Bibliography current world literature. Valvular heart disease.

PMID- 9593543
TI  - Bibliography current world literature. Heart transplantation.

PMID- 9593544
TI  - Bibliography current world literature. Prevention.

PMID- 9593545
TI  - New developments in mitral valve repair.
AB  - The etiology of mitral valve disease is changing. The predominance of rheumatic
      pathology has given way to degenerative pathology in an increasingly elderly
      population. Mitral valve conservation by repair rather than replacement has
      several advantages. Repair is associated with a lower incidence of
      thromboembolism, hemolysis, and infectious endocarditis. For patients in sinus
      rhythm, thromboembolism is rare and anticoagulation can be discontinued. Repair
      also is associated with improved long-term survival. This article reviews the
      current literature on different types of surgical techniques for repair of the
      mitral valve and discusses future trends.

PMID- 9593546
TI  - Evolving experience with cryopreserved mitral valve allografts.
AB  - Allograft valves have been used for aortic valve replacement (AVR) for 35 years
      with excellent results. Early attempts at mitral valve replacement (MVR) with
      mitral valve allograft were unsuccessful mainly due to technical issues of
      measurement of appropriate graft size, difficulty of reimplantation, and early
      dehiscence of the papillary muscle anastomosis. Recently, interest in this
      procedure has been rekindled by successful laboratory experiments with mitral
      valve allograft implantation and improved understanding of the mitral valve
      apparatus from extensive mitral valve repair experience. In this article, we
      discuss the rationale for allograft use, the historical perspective of allograft
      use, and technical problems, along with current solutions and clinical outcomes
      of MVR with mitral valve allograft. Tricuspid valve replacement (TVR) with
      allograft mitral valve also is briefly discussed.

PMID- 9593548
TI  - Technical considerations for valve repair in patients with congenital heart
      disease.
AB  - Valve repair is a critical element in the surgical treatment of congenital heart
      disease. Growing children require a longitudinal management strategy not commonly
      necessary in adult cardiac surgery. The use of valve prostheses poses unique
      problems in children, not only due to size limitations, but also to difficulties
      with chronic medical management. For these reasons, considerable effort is given
      to repairing even severely malformed valves in pediatric patients. This article
      provides a brief overview of some commonly used techniques in reparative valve
      surgery in children.

PMID- 9593547
TI  - Aortic valve disease in Marfan syndrome.
AB  - The Marfan syndrome patient undergoes care by many different physicians for the
      treatment of the varied systems affected by this connective tissue disorder. The
      most frequent visits are to a cardiologist, with referral to a cardiovascular
      surgeon who attends to the problems of dilatation and dissection of the ascending
      aorta. Follow-up is lifelong. Although currently some surgeons prefer to
      resuspend rather than replace the aortic valve, composite valve graft replacement
      for aortic root dilatation and aortic valve insufficiency has steadily improved
      patient outcome. At the same time, the almost daily discoveries of genetic
      science show great promise in eliminating connective tissue disorders such as
      Marfan syndrome in the not-too-distant future.

PMID- 9593549
TI  - Minimally invasive valve surgery.
AB  - Minimally invasive surgical techniques have proliferated at a staggering rate in
      the last decade. Cardiac surgery has been a late entrant in this process but is
      currently experiencing a surge of interest in and techniques for minimally
      invasive approaches. Cardiac valve surgery has seen a rapid and ongoing evolution
      of minimally invasive approaches that, it is hoped, will decrease patient
      discomfort, operative morbidity, length of hospitalization, and cost, improve
      cosmetic healing, and facilitate return to normal function while not compromising
      short- or long-term outcomes of the surgical procedure. This article examines the
      evolution of recent experience with minimally invasive valve surgery and
      emphasizes the surgical considerations surrounding 1) the choice of incision, 2)
      access techniques for cardiopulmonary bypass (CPB), 3) methods of myocardial
      protection, 4) techniques for aortic occlusion, and 5) atrial incisions for
      exposure of the mitral valve. The results of early and currently available series
      are also reviewed.

PMID- 9593550
TI  - Do calcium channel blockers and HMG-CoA reductase inhibitors attenuate allograft
      arteriopathy?
AB  - Recent epidemiologic studies of the risk factors for early and late phases of
      transplant coronary artery disease (TxCAD) have identified metabolic
      abnormalities such as hyperlipidemia and insulin resistance as important risk
      factors, independent of rejection. In randomized trials, calcium channel blockers
      and hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors were shown to
      decrease coronary artery intimal thickening and stenosis. Furthermore, HMG-CoA
      reductase inhibitors significantly decreased allograft loss during the first year
      after transplantation, resulting in a survival benefit, independent of TxCAD and
      cholesterol lowering. Prevention of acute allograft failure is consistent with
      known immunomodulatory actions of HMG-CoA reductase inhibitors, and the effects
      of calcium blockers in preventing TxCAD might have an immunologic basis by virtue
      of alterations of cyclosporine pharmacodynamics. Hence these two strategies for
      targeting antigen-independent mechanisms should lead to a significant reduction
      in the incidence of TxCAD, a goal that has until this time defied all the
      advances in immunosuppression during the past three decades of heart
      transplantation.

PMID- 9593551
TI  - Mycophenolate mofetil in cardiac transplantation.
AB  - Mycophenolate mofetil (MMF) is a new immunosuppressive agent with proven efficacy
      in the prevention of rejection in renal transplant recipients. Clinical studies
      in heart transplantation have suggested efficacy in patients with refractory and
      persistent rejection. A large multicenter randomized primary prevention trial in
      heart transplant patients has just been completed and suggests benefits of MMF in
      survival and treated rejection episodes. This drug appears to be well tolerated
      without significant increase in infection or other complications. MMF appears to
      be an important immunosuppressive agent in cardiac transplant recipients.

PMID- 9593552
TI  - Prevention and treatment of cytomegalovirus infection and disease in heart
      transplant recipients.
AB  - Despite advances in prophylaxis and treatment, cytomegalovirus (CMV) infection
      remains a significant problem in the solid-organ transplant recipient. In
      addition to the clinical manifestations of CMV infection, there is also the
      immunosuppressive effect of CMV, which confers increased risk for fungal and
      other opportunistic infections. In reference to heart transplant recipients, the
      possible connection between CMV infection and rejection or CMV infection and
      allograft vasculopathy are areas of active research. Recent diagnostic advances,
      such as the CMV antigenemia assay and CMV-DNA detection by polymerase chain
      reaction or direct hybrid capture, have enabled early detection and monitoring of
      CMV infection and have raised the question of the implications of asymptomatic
      viremia. A wide variety of prophylactic strategies have been evaluated in heart
      and other solid-organ transplant recipients, including antiviral agents, globulin
      preparations, combinations of these therapies, and pre-emptive treatment
      strategies based on early detection or identification of a high-risk subset of
      patients. Many of these regimens have demonstrated efficacy in certain groups of
      patients, but a consensus has yet to emerge in terms of a single preferable
      strategy. Future advances on the horizon include the development of newer
      antiviral agents and a vaccine.

PMID- 9593553
TI  - Treatment of diabetes mellitus to reduce its chronic cardiovascular
      complications.
AB  - Cardiovascular complications are a major cause of morbidity and mortality in
      patients with diabetes mellitus. Diabetes is a heterogeneous, complex metabolic
      disorder, and it is unlikely that control of hyperglycemia alone will eliminate
      the excess of cardiac, cerebral, and peripheral vascular diseases found in
      diabetic patients. In the care of the diabetic patient, glucose levels should be
      reduced to normal if possible. In addition, however, it is crucial to evaluate
      and, if necessary, to correct abnormalities in lipids, blood pressure, and
      hemostasis. The importance of reducing levels of insulin and insulin resistance
      is not yet clear. Although many questions remain to be answered, available data
      strongly suggest that patients with diabetes benefit from more aggressive and
      comprehensive treatment.

PMID- 9593555
TI  - What have we learned from the calcium channel blocker controversy?

PMID- 9593554
TI  - The role of hormone replacement therapy in preventing coronary artery disease in
      women.
AB  - Many reports show a reduction in cardiovascular disease events in cohorts of
      women taking postmenopausal hormone replacement. Newer reports detail the
      possible mechanisms for reduction in cardiac events, including beneficial changes
      in arterial function and lipid metabolism. Clinical studies now show that
      combination estrogen and progestin therapy appears to also result in a reduction
      in cardiovascular risk, but women are receiving mixed messages about why they
      should or should not take hormones and many discontinue or never start therapy.
      Several organizations have provided guidelines for evaluating the individual risk
      benefit ratio for hormone replacement therapy for a given woman. Until randomized
      clinical trials are reported, adherence to established guidelines for treatment
      is the recommended course of action.

PMID- 9593556
TI  - Arrhythmogenic right ventricular cardiomyopathies: clinical forms and main
      differential diagnoses.

PMID- 9593557
TI  - Elevated levels of 8-iso-prostaglandin F2alpha in pericardial fluid of patients
      with heart failure: a potential role for in vivo oxidant stress in ventricular
      dilatation and progression to heart failure.
AB  - BACKGROUND: It has been suggested that oxidant stress may play a role in the
      pathophysiology of heart failure. However, no definitive information is available
      because most previous approaches used to measure oxidant stress are nonspecific,
      inaccurate, and unreliable. METHODS AND RESULTS: To evaluate oxidant stress in
      the heart, we measured pericardial fluid levels of 8-iso-prostaglandin F2alpha (8
      iso-PGF2alpha), a specific and quantitative marker of oxidant stress in vivo, in
      a series of 51 consecutive patients with ischemic and/or valvular heart disease
      referred for cardiac surgery. Pericardial levels of 8-iso-PGF2alpha were
      correlated with the functional severity of heart failure (NYHA classification)
      and with echocardiographic indices of ventricular dilatation measured by
      independent physicians. Pericardial levels of 8-iso-PGF2alpha were significantly
      increased in patients with symptomatic heart failure compared with asymptomatic
      patients and gradually increased with the functional severity of heart failure
      (P=.0003). In addition, pericardial levels of 8-iso-PGF2alpha were significantly
      correlated with left ventricular end-diastolic and end-systolic diameters (P=.008
      and .026, respectively). CONCLUSIONS: Pericardial levels of 8-iso-PGF2alpha
      increase with the functional severity of heart failure and are associated with
      ventricular dilatation. These data suggest an important role for in vivo oxidant
      stress on ventricular remodeling and the progression to heart failure.

PMID- 9593558
TI  - Prospective study of calcium channel blocker use, cardiovascular disease, and
      total mortality among hypertensive women: the Nurses' Health Study.
AB  - BACKGROUND: In several observational studies, patients prescribed calcium channel
      blockers had higher risks of cardiovascular diseases and mortality than those
      prescribed other antihypertensive medications. We explored these associations in
      the Nurses' Health Study. METHODS AND RESULTS: A total of 14 617 women who
      reported hypertension and regular use of diuretics, beta-blockers, calcium
      channel blockers, ACE inhibitors, or a combination in 1988 were included in the
      analyses. Cardiovascular events and deaths were ascertained through May 1, 1994.
      We documented 234 cases of myocardial infarction. Calcium channel blocker
      monodrug users had an age-adjusted relative risk (RR) of myocardial infarction of
      2.36 (95% CI, 1.43 to 3.91) compared with those prescribed thiazide diuretics.
      Women prescribed calcium channel blockers had a higher prevalence of ischemic
      heart disease. After adjustment for these and other coronary risk factors, the RR
      was 1.64 (95% CI, 0.97 to 2.77). Comparing the use of any calcium channel blocker
      (monodrug and multidrug users) with that of any other antihypertensive agent, the
      adjusted RR was 1.42 (95% CI, 1.01 to 2.01). An association between calcium
      channel blocker use and myocardial infarction was apparent among women who had
      ever smoked cigarettes (covariate-adjusted RR, 1.81; 95% CI, 1.20 to 2.72) but
      not among never-smokers (RR, 0.94; 95% CI, 0.48 to 1.84). CONCLUSIONS: In
      analyses adjusted only for age, we found a significant elevation in RR of total
      myocardial infarction among women who used calcium channel blockers compared with
      those who did not. After adjustment for comorbidity and other covariates, the RR
      was reduced. Whether the remaining observed elevated risk is real, or a result of
      residual confounding by indication, or chance, or a combination of the above
      cannot be evaluated with certainty on the basis of these observational data.

PMID- 9593559
TI  - Extended mortality benefit of early postinfarction reperfusion. GUSTO-I
      Angiographic Investigators. Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries Trial.
AB  - BACKGROUND: Reperfusion therapy for myocardial infarction, understood to reduce
      mortality by preserving left ventricular function, was initially expected to
      provide increasing benefits over time. Surprisingly, large controlled
      thrombolysis trials demonstrated maximum benefit at 4 to 6 weeks with no
      subsequent increased treatment advantage. Such studies, however, compared groups
      by assigned treatment, not physiological effectiveness. METHODS AND RESULTS: We
      calculated 2-year survival differences among 2431 myocardial infarction patients
      according to early infarct artery patency and outcome left ventricular ejection
      fraction using Kaplan-Meier curves. Hazard ratios for significant survival
      determinants were derived from Cox regression models. Two-year vital status
      (minimum, 688 days) was determined in 2375 patients (97.7%). A substantial
      mortality advantage for early complete reperfusion (Thrombolysis in Myocardial
      Infarction [TIMI] grade 3) and for preserved ejection fraction occurred beyond 30
      days. The unadjusted hazard ratio for the TIMI 3 group compared with lesser
      grades at 30 days was 0.57 (95% confidence interval [CI], 0.35 to 0.94) and 30
      days to > or = 688 days was 0.39 (95% CI, 0.22 to 0.69). Consequently, early TIMI
      3 flow was associated with approximately a 3 patient per 100 mortality reduction
      the first month with an additional 5 lives per 100 from 30 days to 2 years. For
      ejection fraction >40% compared with < or = 40%, the unadjusted hazard ratio was
      0.25 (95% CI, 0.16 to 0.37) at 30 days and 0.22 (95% CI, 0.15 to 0.33) after 30
      days through 2 years (lives saved, approximately 9 and 11 per 100, respectively).
      CONCLUSIONS: Successful reperfusion and myocardial salvage produce significant
      mortality benefits that are amplified beyond the initial 30 days.

PMID- 9593560
TI  - Noninvasive assessment of significant left anterior descending coronary artery
      stenosis by coronary flow velocity reserve with transthoracic color Doppler
      echocardiography.
AB  - BACKGROUND: Coronary flow reserve has been considered an important diagnostic
      index of the functional significance of coronary artery stenosis. With Doppler
      technique, it has been assessed as the ratio of hyperemic to basal coronary flow
      velocity (coronary flow velocity reserve [CFVR]) by invasive or semiinvasive
      methods with a Doppler catheter, a Doppler guide wire, and a transesophageal
      Doppler echocardiographic probe. Recent technological advancement in
      transthoracic Doppler echocardiography (TTDE) provides measurement of coronary
      flow velocity in the distal portion of the left anterior descending coronary
      artery (LAD) and may be useful in the noninvasive CFVR measurement. The purpose
      of this study was to evaluate the value of CFVR determined by TTDE for the
      assessment of significant LAD stenosis. METHODS AND RESULTS: We studied 36
      patients who underwent coronary angiography for the assessment of coronary artery
      disease. The study population consisted of 12 patients with significant LAD
      stenosis (group A) and 24 patients without significant LAD stenosis (group B).
      With TTDE, coronary flow velocities in the distal LAD were recorded at rest and
      during hyperemia induced by intravenous infusion of adenosine (0.14 mg x kg(-1) x
      min(-1)) under the guidance of color Doppler flow mapping. Adequate spectral
      Doppler recordings of coronary flow in the distal LAD for the assessment of CFVR
      were obtained in 34 of 36 study patients (94%). The peak and mean diastolic
      coronary flow velocities at baseline did not differ between groups A and B
      (23.6+/-10.3 versus 22.9+/-6.6 cm/s and 16.4+/-8.6 versus 14.5+/-4.0 cm/s,
      respectively). However, the peak and mean coronary flow velocities during
      hyperemia in group A were significantly smaller than those in group B (35.6+/
      16.3 versus 54.2+/-16.3 cm/s and 24.7+/-13.1 versus 37.9+/-13.0 cm/s,
      respectively; P<.01). There were significant differences in CFVR obtained from
      peak and mean diastolic velocity between groups A and B (1.5+/-0.2 versus 2.4+/
      0.4 and 1.5+/-0.2 versus 2.6+/-0.4, respectively; P<.001). A CFVR from peak
      diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 82% for the
      presence of significant LAD stenosis. A CFVR from mean diastolic velocity <2.0
      had a sensitivity of 92% and a specificity of 86% for the presence of significant
      LAD stenosis. CONCLUSIONS: CFVR determined by TTDE is useful in the noninvasive
      assessment of significant stenotic lesion in the LAD.

PMID- 9593561
TI  - Prognostic value of vasodilator myocardial perfusion imaging in patients with
      left bundle-branch block.
AB  - BACKGROUND: The prognostic value of tomographic myocardial perfusion imaging with
      dipyridamole or adenosine in patients with left bundle-branch block has not been
      established. METHODS AND RESULTS: The study group consisted of 245 patients with
      left bundle-branch block who underwent tomographic (single photon emission
      tomography) myocardial perfusion imaging with thallium-201 (n=173) or technetium
      99m sestamibi (n=72) and either dipyridamole (n=153) or adenosine (n=92) stress.
      Patients were prospectively classified into two groups. Patients were classified
      as "high risk" if they had (1) a large severe fixed defect (n=28), (2) a large
      reversible defect (n=36), or (3) cardiac enlargement and either increased
      pulmonary uptake (thallium) or a decreased resting ejection fraction (sestamibi)
      (n=20). The remaining 161 patients (66% of the study group) were at "low risk."
      Follow-up was 99% complete at 3+/-1.4 years. Three-year overall survival was 57%
      in the high-risk group compared with 87% in the low-risk group (P<.0001).
      Survival free of cardiac death/nonfatal myocardial infarction/cardiac
      transplantation was 55% in the high-risk group and 93% in the low-risk group
      (P<.0001). The presence of a high-risk scan had significant incremental
      prognostic value after adjustment for age, sex, diabetes, and previous myocardial
      infarction (P<.0001). Patients with a low-risk scan had an overall survival that
      was not significantly different from that of a US age-matched population (P=.86).
      CONCLUSIONS: Tomographic myocardial perfusion imaging with adenosine or
      dipyridamole stress provides important prognostic information in patients with
      left bundle-branch block, which is incremental to clinical assessment.

PMID- 9593562
TI  - Arrhythmogenic right ventricular cardiomyopathy and fatty replacement of the
      right ventricular myocardium: are they different diseases?
AB  - BACKGROUND: The relationship between arrhythmogenic right ventricular
      cardiomyopathy (ARVC) and pure fat replacement of the right ventricle is unclear.
      METHODS AND RESULTS: Myocardial thickness, epicardial fat thickness, percent
      fibrosis, and intramyocardial fat infiltration were measured in 16 sections each
      from 25 hearts with typical (fibrofatty) ARVC, 7 hearts with fat replacement of
      the right ventricle without fibrosis (FaRV), and 18 control hearts from patients
      who died of noncardiac causes. Patients with fibrofatty ARVC were younger than
      those with FaRV (31+/-14 versus 44+/-13 years, P=.02), more likely to have a
      history of arrhythmias or a family history of premature sudden death (56% versus
      0%, P=.01), more likely male (80% versus 29%, P=.02), and less likely to have
      coexisting conditions that might have predisposed to sudden death (12% versus
      86%, P<.001). Fibrofatty ARVC was characterized by right ventricular myocardial
      thinning, fat infiltration of the anterobasal and posterolateral apical right
      ventricle, subepicardial left ventricular fibrofatty replacements (64%), myocyte
      atrophy (96%), and lymphocytic myocarditis (80%). FaRV showed normal or increased
      myocardial thickness, a diffuse increase in intramyocardial and epicardial fat,
      little inflammation, and an absence of myocardial atrophy. Intramyocardial fat
      was frequently seen in normal hearts, especially in the anteroapical region, but
      was less extensive than in fibrofatty ARVC and FaRV. CONCLUSIONS: ARVC is a
      familial arrhythmogenic disease characterized by fibrofatty replacement of
      myocytes with scattered foci of inflammation. Fat infiltration per se is probably
      a different process that should not be considered synonymous with ARVC.

PMID- 9593563
TI  - Improvement of repolarization abnormalities by a K+ channel opener in the LQT1
      form of congenital long-QT syndrome.
AB  - BACKGROUND: This study used monophasic action potential (MAP) to examine the
      effect of nicorandil, a K+ channel opener, on repolarization abnormalities
      induced by epinephrine in the LQT1 form of congenital long-QT syndrome in which
      the KvLQT1 mutation underlies the defect in the channel responsible for the
      slowly activating component of the delayed rectifier potassium current. METHODS
      AND RESULTS: MAPs were recorded simultaneously from two or three sites on the
      right ventricular and left ventricular endocardium in 6 patients with a
      congenital form of LQT1 syndrome with KvLQT1 defect (17 sites) and 8 control
      patients (24 sites). In LQT1 patients, epinephrine infusion prolonged the QT
      interval and 90% MAP duration (MAPD90) and increased the dispersion of MAPD90.
      Epinephrine also induced early after depolarizations (EADs) as well as
      ventricular premature complexes (VPCs) in 2 of the 6 patients. Nicorandil during
      epinephrine infusion abbreviated the QT interval and MAPD90, decreased the
      dispersion of MAPD90, and abolished the EADs as well as the VPCs in 1 patient.
      Addition of propranolol completely reversed the effect of epinephrine in
      prolonging the QT interval and MAPD90 and increasing the dispersion and
      eliminated the EADs and VPCs in another patient. In control patients, the effect
      of epinephrine and that of additional nicorandil and propranolol on
      repolarization parameters were much less than in the LQT1 patients. CONCLUSIONS:
      Our results suggest that nicorandil, a K+ channel opener, improves repolarization
      abnormalities in the LQT1 form of congenital long-QT syndrome with KvLQT1 defect.

PMID- 9593564
TI  - Acceleration of typical atrial flutter due to double-wave reentry induced by
      programmed electrical stimulation.
AB  - BACKGROUND: Acceleration of reentrant tachycardia induced by programmed
      electrical stimulation is a well-documented phenomenon, but the mechanisms remain
      poorly understood. METHODS AND RESULTS: Twelve patients with typical atrial
      flutter were studied. Activation sequence of the underlying reentrant circuit was
      recorded by multiple multipolar electrodes placed in the right atrium. In five
      patients, 27 episodes of atrial flutter acceleration were induced by single
      extrastimuli delivered in the isthmus between the tricuspid annulus and
      eustachian ridge (TA-ER isthmus) and one by rapid overdrive atrial pacing.
      Analyses of the activation sequences, intracardiac electrograms, and 12-lead
      surface ECG P-wave morphology indicated that the acceleration was caused by two
      successive activation wave fronts circulating in the same direction along the
      same reentrant circuit (double-wave reentry, DWR). DWR was induced only within a
      narrow range of coupling interval, from 2 to 45 ms beyond the effective
      refractory period, and was associated with unidirectional antidromic block of the
      paced impulse. Patients with DWR had a shorter effective refractory period
      (138.8+/-13.4 versus 163.8+/-12.2 ms, P<.015) and larger excitable gap (124.0+/
      22.6 versus 83.2+/-13.2 ms, P<.009) compared with patients without inducible DWR.
      All of the DWR episodes were transient. Most (78.6%) terminated after one of the
      double wave fronts was blocked in the TA-ER isthmus. CONCLUSIONS: DWR is one of
      the mechanisms responsible for programmed electrical stimulation-induced atrial
      flutter acceleration in human subjects. Its induction requires a sufficient
      excitable gap and antidromic unidirectional block of the paced impulse in the TA
      ER isthmus. In addition, the TA-ER isthmus is the usual site of DWR termination.

PMID- 9593565
TI  - Analysis of the effect of flow rate on the Doppler continuity equation for
      stenotic orifice area calculations: a numerical study.
AB  - BACKGROUND: Flow-rate dependencies of the Doppler continuity equation are
      addressed in this study. METHODS AND RESULTS: By use of computational fluid
      dynamic (CFD) software with turbulence modeling, three-dimensional axisymmetric
      models of round stenotic orifices were created. Flow simulations were run for
      various orifice area sizes (0.785, 1.13, 1.76, and 3.14 cm2) and flow rates (0.37
      to 25.0 L/min). Reynolds numbers ranged from 100 to 8000. Once adequate
      convergence was obtained with each simulation, the location of the vena contracta
      was determined. For each run, maximum and average velocities across the cross
      section of the vena contracta were tabulated and vena contracta cross-sectional
      area (effective orifice area) determined. The difference between the maximum
      velocity and the average velocity at the vena contracta was smallest at high-flow
      states, with more of a difference at low-flow states. At lower-flow states, the
      velocity vector profile at the vena contracta was parabolic, whereas at high-flow
      states, the profile became more flattened. Also, the effective orifice area (vena
      contracta cross-sectional area) varied with flow rate. At moderate-flow states,
      the effective orifice area reached a minimum and expanded at low- and high-flow
      states, remaining relatively constant at high-flow states. CONCLUSIONS: We have
      shown that significant differences exist between the maximum velocity and the
      average velocity at the vena contracta at low flow rates. A likely explanation
      for this is that viscous effects cause lower velocities at the edges of the vena
      contracta at low flow rates, resulting in a parabolic profile. At higher-flow
      states, inertial forces overcome viscous drag, causing a flatter profile.
      Effective orifice area itself varies with flow rate as well, with the smallest
      areas seen at moderate-flow states. These flow-dependent factors lead to flow
      rate-dependent errors in the Doppler continuity equation. Our results have strong
      relevance to clinical measurements of stenotic valve areas by use of the Doppler
      continuity equation under varying cardiac output conditions.

PMID- 9593566
TI  - Pharmacological strategies for improving diastolic dysfunction in the setting of
      chronic pulmonary hypertension.
AB  - BACKGROUND: Right ventricular (RV) hypertrophy is an adaptive process that occurs
      in the setting of chronic pulmonary hypertension (CPH) and can lead to
      alterations in normal RV diastolic properties. This study was designed to
      investigate the effects of NO and milrinone on RV diastolic dysfunction in the
      setting of CPH and RV hypertrophy by use of a canine model of monocrotaline
      pyrrole (MCTP)-induced CPH. METHODS AND RESULTS: Sixteen mongrel dogs (22 to 24
      kg) were used. Animals underwent percutaneous pulmonary artery (PA)
      catheterization to measure pulmonary hemodynamics before and 8 weeks after
      injection of 3 mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after
      injection, all hearts were instrumented with a PA flow probe, sonomicrometric
      dimension transducers, and micromanometers. Data were collected at baseline and
      after both NO and milrinone administration. Diastolic properties were quantified
      by use of the end-diastolic pressure-volume relationship and the time constant of
      ventricular isovolumic relaxation. Eight weeks after injection, significant
      increases in the PA pressure and pulmonary vascular resistance were observed in
      MCTP dogs. Significant worsening of RV diastolic function occurred in association
      with significant increases in the ratio of RV dry weight to LV+septal dry weight.
      NO and milrinone administration both led to significant improvements in RV
      diastolic properties. CONCLUSIONS: In the setting of MCTP-induced CPH,
      significant worsening of RV diastolic function was observed in association with
      significant increases in the ratio of RV dry weight to LV+septal dry weight,
      suggesting that these changes are partially due to RV hypertrophy. The
      significant improvement in RV diastolic properties after both NO and milrinone
      administration suggests that these agents may be effective forms of
      pharmacological therapy for improving RV diastolic dysfunction in the setting of
      CPH.

PMID- 9593567
TI  - Effects of atrial defibrillation shocks on the ventricles in isolated sheep
      hearts.
AB  - BACKGROUND: The effects of cardioversion of atrial fibrillation on the activation
      sequence of the ventricles have not been previously studied. In this study we
      examined the events in the ventricle that follow the application of atrial
      defibrillatory shocks. METHODS AND RESULTS: We used video imaging technology to
      study the sequence of activation on the surface of the ventricles in the
      Langendorff-perfused sheep heart. We recorded transmembrane potentials
      simultaneously from over 20000 sites on the epicardium before and after biphasic
      shocks applied by a programmable atrial defibrillator. The first epicardial
      activation after the shock depended on both the voltage and timing of the shock.
      During ventricular diastole shocks as low as 10 V produced ventricular
      excitation, although the time between the shock and the first epicardial
      activation (latency) was approximately 30 ms. As the shock voltage was increased
      to 120 V, latency decreased to zero and the entire epicardium was depolarized
      within 30 ms. For 120-V shocks delivered late in systole, the depolarization
      sequence produced by the shock was similar to the previous repolarization
      sequence. Shocks of 120 V applied 150 to 300 ms after the previous ventricular
      excitation induced ventricular fibrillation. Ventricular fibrillation was induced
      by multiple focal beats after the shock, which produced waves that propagated but
      broke down into reentry within regions of high repolarization gradients.
      CONCLUSIONS: These results demonstrate that atrial defibrillation shocks excite
      the ventricles even at low shock voltages. In addition, ventricular fibrillation
      can be induced by shocks given in the vulnerable period by producing focal
      patterns that break down into reentrant waves.

PMID- 9593568
TI  - Distribution of atrial and nodal cells within the rabbit sinoatrial node: models
      of sinoatrial transition.
AB  - BACKGROUND: In the sinoatrial node (SAN) the course of the action potential
      gradually changes from the primary pacemaker region toward the atrium. It is not
      known whether this gradient results from different intrinsic characteristics of
      the nodal cells, from an increasing electrotonic interaction with the atrium, or
      from both. Therefore we have characterized the immunohistochemical,
      morphological, and electrophysiological correlates of this functional gradient.
      METHODS AND RESULTS: The distribution of rabbit nodal myocytes in the SAN has
      been studied by immunohistochemistry. After cell isolation, the
      electrophysiological characteristics of different nodal cell types were measured.
      (1) The staining pattern of a neurofilament protein coincides with the
      electrophysiologically mapped pacemaker region in the SAN. (2) Enzymatic
      digestion of the SAN reveals three morphologically different nodal cell types and
      one atrial type. Of each nodal cell type, neurofilament-positive as well as
      neurofilament-negative myocytes are found. Atrial cells are all neurofilament
      negative. (3) In contrast to previous findings, we observed atrial cells in the
      very center of the SAN. The relative number of atrial cells gradually increases
      from the central pacemaker area toward the atrium. (4) Differences in
      electrophysiological characteristics between individual nodal cells are not
      associated with differences in cell type. CONCLUSIONS: (1) The expression of
      neurofilaments can be used to delineate the nodal area in the intact SAN but is
      not sufficiently sensitive for characterizing all individual isolated nodal
      cells. (2) A fundamentally different organization of the SAN is presented: The
      gradual increase in density of atrial cells from the dominant area toward the
      crista terminalis in the SAN causes a gradual increase of atrial electrotonic
      influence that may be an important cause of the gradual transition of the nodal
      to the atrial type of action potential.

PMID- 9593569
TI  - Thrombolysis for acute myocardial infarction.
AB  - Thrombolytic therapy has been a major advance in the management of acute
      myocardial infarction. Unfortunately, it continues to be underused or is
      administered later than is optimal. Thrombolytic therapy works by lysing infarct
      artery thrombi and achieving reperfusion, thereby reducing infarct size,
      preserving left ventricular function, and improving survival. The most effective
      thrombolytic regimens achieve angiographic epicardial infarct-artery patency in
      only approximately 50% of patients within 90 minutes. Bleeding requiring
      transfusion occurs in approximately 5% of patients and stroke in approximately
      1.8% with these regimens, which include adjunctive aspirin and intravenous
      heparin. There are several ways in which reperfusion rates and thus patient
      outcomes might be improved, such as different dosing regimens of established
      agents; combinations of different agents; improved adjunctive therapy such as
      direct antithrombin agents, low-molecular-weight heparin, or glycoprotein
      IIb/IIIa receptor antagonists; or the development of novel thrombolytic agents
      with enhanced fibrin specificity, resistance to native inhibitors, or prolonged
      half-lives allowing bolus administration. All of these strategies are being
      tested in clinical trials. The best approach currently is to administer
      thrombolytic therapy as soon as possible to all patients without
      contraindications who present within 12 hours of symptom onset and have ST
      segment elevation on the ECG or new-onset left bundle-branch block, unless an
      alternative reperfusion strategy is planned.

PMID- 9593570
TI  - Images in cardiovascular medicine. Floating mobile mass that is probably
      thrombus: a life-threatening complication of mitral stenosis.

PMID- 9593571
TI  - Images in cardiovascular medicine. Fibroelastoma and embolic stroke.

PMID- 9593572
TI  - Association between thrombolytic treatment and the prognosis of hemodynamically
      stable patients with major pulmonary embolism.

PMID- 9593573
TI  - Growth hormone in chronic heart failure.

PMID- 9593574
TI  - Paclitaxel and arterial smooth muscle cell proliferation.

PMID- 9593575
TI  - Prospective study of asymptomatic aortic stenosis.

PMID- 9593576
TI  - Low-energy biphasic waveform defibrillation: evidence-based review applied to
      emergency cardiovascular care guidelines: a statement for healthcare
      professionals from the American Heart Association Committee on Emergency
      Cardiovascular Care and the Subcommittees on Basic Life Support, Advanced Cardiac
      Life Support, and Pediatric Resuscitation.

PMID- 9593577
TI  - Applications of infrared spectroscopy to medical biology.
AB  - This short review presents the great power of Fourier transform infrared (FT-IR)
      spectroscopy in the field of medicinal biology. New spectrometers as well as new
      accessories for sampling have significantly contributed to extend the application
      fields of the infrared techniques. During the past few years, it has been pointed
      out that FT-IR spectroscopy can be used to identify bacteria, to characterize
      neoplasic changes from biopsies, to recognize the various forms of arthritis by
      analysis of synovial fluid. This paper intends also to illustrate two clinical
      chemistry applications: the determination of the fecal lipids by FT-IR
      spectroscopy with an attenuated total reflectance accessory (ATR) and the
      measurement of the carbone monoxide in blood.

PMID- 9593578
TI  - Intracellular and serum stability of liposomal 2',3'-dideoxycytidine. Effect of
      lipid composition.
AB  - The serum and intracellular stability of 2',3'-dideoxycytidine (ddC) encapsulated
      in liposomes having different physicochemical properties have been investigated.
      Results showed that the presence of cholesterol in the lipid composition of
      liposomes resulted in an increased leakage of ddC when incubated in 80% serum at
      37 degrees C. The length of the hydrocarbon chains of the phosphatidylcholine
      component in cholesterol-containing liposomes did not induce major modifications
      in both the efficiency of encapsulation and retention of the antiviral agent. The
      uptake and intracellular stability of the different liposomal formulations have
      also been evaluated as a function of drug concentration in RAW 264.7 macrophages.
      For all liposomal formulations tested, an enhanced uptake of liposome
      encapsulated ddC by macrophages was observed when the liposomal drug
      concentration was increased. In addition, the anionic character of liposomes
      seemed to be an important factor to obtain a high intracellular uptake of ddC.
      The drug release from liposomal ddC-loaded macrophages has also been evaluated in
      serum-free medium. Liposomes having long saturated fatty acyl phospholipids and
      containing 50% (molar ratio) of cholesterol displayed the best stability in the
      intramacrophagic compartments at all liposomal ddC concentrations used. On the
      other hand, although the leakage of ddC from liposomes sterically stabilized with
      polyethyleneglycol chains was similar to that of other cholesterol-containing
      liposomes, the antiviral agent was readily released from cells for all
      concentrations of liposomal ddC tested. In conclusion, these results show that
      the serum stability does not necessarily reflect the intracellular stability, and
      suggest that some lipid components such as cholesterol can modulate the liposomal
      stability of drugs such as ddC in response to the conditions of the environment,
      the properties of the drug used and the nature of interactions between liposomes
      and cells.

PMID- 9593579
TI  - Stability of metallothionein isoforms by capillary zone electrophoresis.
AB  - Stability of isoforms on storage of metallothionein (MT) was investigated by
      capillary zone electrophoresis (CZE) at neutral pH. The mouse liver was removed 1
      day after injection of zinc, and homogenized in 0.25 M sucrose with 100 mM TRIS
      HCl buffer, pH 7.4. The specimens for MT analysis were obtained by two partial
      purification methods, i.e., heat treatment (HT) and ethanol/chloroform
      precipitation (ECP) methods. The specimens were stored at either 4 degrees C or 
      80 degrees C for 1 and 3 days, and peak areas of MT-1 and MT-2 isoforms obtained
      by CZE were compared. When specimens were obtained by HT method, both MT isoforms
      were stable at -80 degrees C within 3 days. However, the peak area of MT-1 stored
      at 4 degrees C was gradually decreased to one third on the 3rd day. The MT-2 peak
      did not decrease the next day, but decreased to 57% on the 3rd day. In contrast,
      peak areas of both MT isoforms decreased remarkably the 1st day, when specimens
      obtained from ECP method were stored at 4 degrees C and -80 degrees C. From these
      results, we conclude that stability of MT isoforms is different depending on the
      purification methods, and MT isoforms are not stable after partial purification,
      especially by ECP method, even if stored at -80 degrees C.

PMID- 9593580
TI  - Inorganic pyrophosphate-phosphohydrolytic activity associated with rat osseous
      plate alkaline phosphatase.
AB  - Purified membrane-bound alkaline phosphatase from rat osseous plate hydrolyzed
      pyrophosphate in the presence of magnesium ions, with a specific activity of 92.7
      U/mg. Optimal apparent pH for pyrophosphatase activity was 8.0 and it remained
      unchanged on increasing the pyrophosphate concentration. In the absence of
      magnesium ions the enzyme had a Km = 88 microM and V = 36.7 U/mg for
      pyrophosphate and no inhibition by excess substrate was observed. Pyrophosphatase
      activity was rapidly destroyed at temperatures above 40 degrees C, but magnesium
      ions apparently protected the enzyme against denaturation. Sodium metavanadate
      (Ki = 1.0 mM) was a competitive inhibitor of pyrophosphatase activity, while
      levamisole (Ki = 8.2 mM) and theophylline (Ki = 7.4 mM) were uncompetitive
      inhibitors. Magnesium ions (K0.5 = 1.7 microM) stimulated pyrophosphatase
      activity, while cobalt (Ki = 48.5 microM) and zinc (Ki = 22.0 microM) ions were
      non-competitive inhibitors. Manganese and calcium ions had no effect on
      pyrophosphatase activity. The Mw of the pyrophosphatase protein was 130 kDa by
      gel filtration, but a value of 65 kDa was obtained by dissociative gel
      electrophoresis, suggesting that it was a dimer of apparently identical subunits.
      These results suggested that pyrophosphatase activity stems from the membrane
      bound osseous plate alkaline phosphatase and not from a different protein.

PMID- 9593581
TI  - Ribonucleic acid treatment alters gene expression in diploid strains of
      Aspergillus nidulans.
AB  - Physical and chemical agents that promote DNA damage can induce high levels of
      mitotic crossing-over in eukaryotic diploid cells. Similarly, foreign DNA
      segments introduced by transformation processes, in the cell genome, can also
      induce mitotic crossing-over as an outcome of the reactions leading to
      chromosomic balance or due to the mechanisms aiming at the integration of the
      exogenous DNA. Zucchi et al. have described a system showing that RNA treatments
      are capable of inducing changes in the genome of haploid receptor strains of
      Aspergillus nidulans. To verify the genetic consequences of this process in
      diploid cells, conidia from two strains of this fungus were protoplastized,
      treated with homologous RNA and analyzed. Alterations in the gene expression and
      in the mitotic crossing-over frequencies between linked markers were detected.
      Among the main observed effects there was a generalized alteration in gene
      expression which was very likely caused by a reversible gene inactivation
      mechanism due to the methylation of cytosine residues. This was confirmed by
      treating the haploid segregants with the hypomethylating agent 5-azacytidine,
      that restored the original gene activity. The presence of a duplicated segment in
      the chromosome I of one of the treated diploids, interfered with the RNA general
      effects on its genome.

PMID- 9593582
TI  - Aberrant regulation of bone trace elements in motheaten and osteopetrosis mutant
      mice.
AB  - Increasing numbers of genetic diseases involving bone development and models for
      these diseases have been identified recently. Analysis of these bone diseases
      have revealed that regulated action of multiple growth factors and subsequent
      signal transduction are essential for normal bone formation. In this paper, two
      murine mutant mice viable motheaten and osteopetrosis are analyzed. Mice with the
      recessive 'viable motheaten' mutation express a severe immunodeficiency syndrome
      and bone defects. Mutations at the motheaten locus were shown to be the result of
      aberrant splicing of the gene encoding hematopoietic cell phosphatase (Hcph).
      Mice homozygous for the osteopetrosis mutation develop congenital osteopetrosis
      due to a severe deficiency of osteoclasts. It has been recognized that bone trace
      element composition analysis helps to define bone-related physiological
      conditions. We have analyzed bone trace element composition in viable motheaten
      and osteopetrosis mutant animal models in this study. In order to gain insights
      into the effects of particular genetic defects on bone trace element composition,
      inductively coupled plasma atomic emissions spectrometry (ICP-AES) analysis was
      performed. Marked changes in bone trace element levels were found in limb bones
      of viable motheaten and osteopetrosis mutant mice. An assessment of these trace
      element spectrum in the two mutant models with respect to each genetic defects
      are discussed in this paper.

PMID- 9593583
TI  - The human cytomegalovirus IE2 86 kDa protein elevates p53 levels and
      transactivates the p53 promoter in human fibroblasts.
AB  - Human cytomegalovirus (HCMV), a herpesvirus, has previously been reported to
      elevate cellular p53 levels within infected human fibroblasts. Since this
      elevation was reported to be due to the expression of HCMV immediate early (IE)
      gene products within the fibroblasts, and the HCMV immediate early region encodes
      several predominant proteins, the identity of the protein responsible for this
      elevation was investigated. We report that the HCMV IE2 86 kDa protein was
      clearly found to be the major immediate early protein responsible for elevating
      p53 levels within the fibroblasts. We also report that the HCMV IE2 86 kDa
      protein was found to transactivate the p53 promoter 5-6 fold, thus explaining the
      5-6 fold rate of increased p53 protein synthesis we find in the HCMV infected
      fibroblasts. Since transactivation of the p53 promoter was observed in IE2 86 kDa
      transfected as well as in HCMV infected fibroblasts, transactivation of the p53
      gene, therefore, is part of the mechanism HCMV uses to elevate p53 levels in
      infected fibroblasts. This is the first report to implicate the HCMV IE2 86 kDa
      protein in the elevation of p53 levels in fibroblasts, as well as in the
      transactivation of the p53 promoter in these cells.

PMID- 9593584
TI  - Induction of p34cdc2 in mouse parotid glands upon activation of beta1-adrenergic
      receptors.
AB  - Dramatic morphological, biochemical and cytological changes occur in parotid
      glands of rats and mice which have been treated with the beta-adrenergic receptor
      agonist isoproterenol (Ipr). Changes include glandular hypertrophy, induction of
      tissue-specific proline-rich proteins (PRPs), increases in cAMP, and occurrence
      of polyploidy. Similar changes also occur after feeding mice polyphenolic
      compounds commonly referred to as tannins. Data are presented which show that
      changes in cell cycle proteins are due to stimulation of the beta-adrenergic
      receptor by either isoproterenol or tannin treatment of mice. Both p34cdc2 mRNA
      and protein levels were elevated dramatically after mice were treated. Induction
      of p34cdc2 occurred within 24 hrs. and was transient during treatment. The beta1
      adrenergic receptor antagonist atenolol blocked both tissue-specific expression
      of proline-rich proteins and induction of p34cdc2. Coincident with the increase
      in p34cdc2, cyclin-dependent kinase complexes containing cyclins A and B
      increased forty- and ten-fold, respectively. These results show that in mouse
      parotid glands activation of the beta1-adrenergic receptor by either the
      administration of isoproterenol or ingestion of dietary tannins induces synthesis
      of p34cdc2 and most likely contributes to the occurrence of polyploidy.

PMID- 9593585
TI  - Early gene expression of both RNA polymerase I transcription factors UBF1 and
      UBF2 precedes ribosomal RNA synthesis during lymphocyte mitogenic stimulation.
AB  - Phytohaemagglutinin stimulates lymphoid cells to initiate active cell division
      which is tightly coordinated with transcription of ribosomal RNA genes. Nuclear
      Run-On assays demonstrated that treatment of peripheral blood lymphocytes with
      PHA (10 microg/ml) resulted in maximal rRNA synthesis after 64 hrs. In contrast,
      mRNA levels for upstream binding factor (UBF)1 and UBF2, as measured by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting, increased
      relatively rapidly within 3 to 6 hrs. and remained elevated for at least the next
      60 hrs. We further showed that exponentially growing cells of promyelocytic
      leukemia line HL-60 contained the same amounts of UBF1 and UBF2 mRNAs as
      phytohaemagglutinin (PHA)-stimulated lymphocytes for 6 hrs. Growth arrest of HL
      60 cells, caused by 10 nM phorbol ester 12-O-tetradecanoylphorbol-13-acetate
      (TPA)-induced monocytic/macrophage-like differentiation for 72 hrs., has been
      accompanied by a 50% decrease in UBF1/2 mRNAs expression. The lowest
      concentrations of UBF1/2 mRNAs were revealed in non-dividing terminally
      differentiated granulocytes. Regardless the activity of RNA polymerase I
      transcription and cell division rate, UBF1 mRNA levels prevailed over UBF2 mRNA
      levels in all human blood cell populations tested. Our results suggest that UBF
      gene expression is an important regulatory mechanism involved in the acceleration
      and possibly deceleration of rDNA transcription observed during mitogenic
      stimulation and inhibition of blood cells.

PMID- 9593586
TI  - Chloride-sulphate exchange chemically measured in human erythrocyte ghosts.
AB  - The purpose of this paper is to provide a clear description of a new chemical
      method to measure and analyze the net anion exchange (Cl-/SO4--) in resealed
      human erythrocyte ghosts. With this technique, we measured the influx of an
      inorganic divalent anion (SO4--) against a monovalent anion (Cl-) as a function
      of temperature. We found an apparent activation enthalpy Ea of 21-24 Kcal/mol.
      Besides the Cl-/SO4-- influx pH - dependence, measured under condition of
      electric anion equilibrium, shows a bell shape with a maximum around pH 6.3. In
      addition we accounted for the extracellular pH changes during the exchange of
      chloride for sulphate across the erythrocyte ghosts when bicarbonate is present
      in the medium. The pH drops sharply, then increases for the remaining
      experimental time course.

PMID- 9593587
TI  - The peripheral nerve and the neuromuscular junction are affected in the tenascin
      C-deficient mouse.
AB  - A thorough examination of the structure and plasticity of the neuromuscular
      system was performed in tenascin-C mutant mice deficient in tenascin-C. The study
      of the peripheral nerve revealed a number of abnormal features. In the motor
      nerve, numerous unmyelinated and myelinated fibers with degraded myelin were
      present. Schwann cell processes often enclosed degenerative terminals. Transgene
      (beta-galactosidase) expression analyzed at the ultrastructural level was found
      to be unequally distributed in the mutant's neuromuscular tissues. At the NMJ,
      preterminal disorganization was prevalent. Some axon terminals exhibited abnormal
      overgrowth. A surprising lack of beta-galactosidase expression at some cellular
      sites known to possess tenascin-C in wild type mice correlated best with marked
      changes in the cytoarchitecture of the peripheral nerve and NMJ. In some other 
      but not all- cellular sites which normally express the molecule,
      immunofluorescence analysis suggested the presence of significant but low levels
      of tenascin-C-like immunoreactivity together with beta-galactosidase expression.
      Messenger RNA detection by RT-PCR confirmed the presence of low amounts of
      tenascin-C mRNA in skeletal muscle suggesting that the mice deficient in tenascin
      C are not complete knock-outs of this gene, but low-expression mutants. Following
      in vivo injections of botulinum type-A toxin, we observed a greatly reduced
      sprouting response of the motor nerves in tenascin-C mutant mice. We also
      observed that N-CAM and beta-catenin were overexpressed in the mutant. Our
      results suggest that tenascin-C is involved both in stabilization and in
      plasticity of the NMJ.

PMID- 9593588
TI  - Neuropeptide FF, pain and analgesia.
AB  - Neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) and the octadecapeptide
      neuropeptide AF (Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln
      Arg-Phe -NH2) were isolated from bovine brain, and were initially characterized
      as anti-opioid peptides. They can oppose the acute effects of opioids and an
      increase in their brain concentrations may be responsible for the development of
      tolerance and dependence to opioids. Numerous experiments suggest a possible
      neuromodulatory role for neuropeptide FF. A precursor protein has been
      identified, in particular in human brain. Neuropeptide FF immunoreactive neurons
      are present only in the medial hypothalamus, and the nucleus of the solitary
      tract, and in the spinal cord in the superficial layers of the dorsal horn and
      areas around the central canal. Depolarization induces a Ca2+-dependent release
      of neuropeptide FF immunoreactivity from the spinal cord. Neuropeptide FF acts
      through stimulation of its own receptors and high densities of specific binding
      sites are found in regions related either to sensory input and visceral functions
      or to the processing of nociceptive messages. In both isolated dorsal root
      ganglion neurons and CA1 pyramidal neurons of the hippocampus, neuropeptide FF
      has little effect of its own but reverses the effects of mu-opioid receptor
      agonists. In agreement with the hypothesized anti-opioid role of neuropeptide FF,
      supraspinal injection lowers the nociceptive threshold and reverses morphine
      induced analgesia in rats. Furthermore, immunoneutralization of neuropeptide FF
      increases endogenous and exogenous opioid-induced analgesia. Similarly,
      microinfusion of neuropeptide FF or neuropeptide FF analogs into the nucleus
      raphe dorsalis, the parafascicular nucleus, or the ventral tegmental area has no
      effect on the nociceptive threshold but inhibits the analgesia induced by co
      injected morphine. Furthermore, infusion of neuropeptide FF into the
      parafascicular nucleus or the nucleus raphe dorsalis reverses the analgesic
      effect of morphine infused into the nucleus raphe dorsalis or the parafascicular
      nucleus, respectively, demonstrating remote interactions between neuropeptide FF
      and opioid systems. By contrast, intrathecal administration of neuropeptide FF
      analogs induces a long lasting, opioid-dependent analgesia and potentiates the
      analgesic effect of morphine. Analgesic effects of neuropeptide FF after
      supraspinal injection could also be observed, for example during nighttime. In
      young mice, (1DMe)Y8Famide (D.Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2), a
      neuropeptide FF analog, increases delta-opioid receptor-mediated analgesia. These
      findings indicate that neuropeptide FF constitutes a neuromodulatory neuronal
      system interacting with opioid systems, and should be taken into account as a
      participant of the homeostatic process controlling the transmission of
      nociceptive information.

PMID- 9593589
TI  - Effects of an alternative reinforcer on intravenous heroin self-administration by
      humans.
AB  - Five heroin-dependent research volunteers, maintained on divided daily oral
      morphine doses, participated in an inpatient study designed to evaluate
      intravenous (i.v.) heroin self-administration when money ($10, $20 or $40) was
      concurrently available. Each morning participants received a single injection of
      heroin (placebo, 6.25, 12.5, 25, or 50 mg/70 kg, i.v.) and each afternoon, they
      had the opportunity to self-administer all or part of the morning dose.
      Participants responded under a progressive-ratio schedule (50, 100, ..., 2800)
      during a 10-trial self-administration task. During each trial, participants could
      respond for 1/10th of the sampled heroin dose or 1/10th of a single money value.
      The progressive-ratio value increased independently for each option. The total
      amount of heroin and/or money chosen during the self-administration task was
      administered at the end of the task. Heroin dose-dependently increased ratings of
      'good drug effect' and 'high', impaired task performance and decreased pupil
      diameter and blood oxygen saturation. Heroin also dose-dependently increased
      progressive-ratio break point values, which varied as a function of the
      alternative money amount. Consistent with previous studies, the present results
      demonstrate that alternative reinforcers, depending on magnitude, are effective
      in reducing heroin use in opioid-dependent individuals.

PMID- 9593590
TI  - Sensitization to the conditioned rewarding effects of morphine and cocaine:
      differential effects of the kappa-opioid receptor agonist U69593.
AB  - The ability of the kappa-opioid receptor agonist U69593 to attenuate the
      sensitization and cross-sensitization which develops to the conditioned rewarding
      effects of morphine and cocaine was examined using an unbiased place-preference
      conditioning procedure. The influence of U69593 treatment upon sensitization and
      cross-sensitization to cocaine was also assessed. Doses of morphine (1.0-5.0 mg
      kg(-1)) which failed to produce a conditioned response in drug-naive rats
      produced marked preferences for the drug-paired place in animals which had
      previously received once daily injections of morphine (5.0 mg kg(-1); s.c.) or
      cocaine (10.0 mg kg(-1); i.p.) for 5 days. Morphine-induced place preferences
      also occurred in animals which had received morphine in combination with U69593
      (0.04-0.32 mg kg(-1); s.c.) on either days 3-5 or 1-5 of the morphine treatment
      regimen. In contrast, morphine failed to produce significant conditioning in
      animals which had received U69593 with cocaine for 5 days. Doses of cocaine (1.0
      5.0 mg kg(-1)) which did not produce a conditioned response in naive rats
      produced preferences for the drug-paired place in animals which had received once
      daily injections of cocaine (10.0 mg kg(-1) day(-1) x 5 days; i.p.) or morphine
      (5.0 mg kg(-1) day(-1) x 5 days; s.c.). No enhancement of cocaine-induced
      conditioning occurred in animals which had received U69593 on days 3-5 or on days
      1-5 of the five-day cocaine treatment. In animals, however, which had received
      U69593 with morphine for 5 days, an enhanced response to cocaine was still seen.
      These findings confirm that sensitization and cross-sensitization develop to the
      conditioned rewarding effects of cocaine and morphine. They also indicate that
      the ability of a kappa-opioid receptor agonist to prevent the development of
      these sensitized responses depends on the sensitizing agent employed. U69593
      prevents sensitization and cross-sensitization induced by cocaine, but does not
      modify morphine-induced sensitization or the cross-sensitization which develops
      to cocaine after morphine administration.

PMID- 9593591
TI  - Selective serotonin reuptake inhibitors potentiate 8-OH-DPAT-induced stimulus
      control in the pigeon.
AB  - The effects of two selective serotonin reuptake inhibitors, fluoxetine and
      citalopram, and a nonselective monoamine reuptake inhibitor, imipramine, were
      characterized in pigeons that had been trained to discriminate 0.64 mg/kg of 8
      hydroxy-(2-di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), a 5-HT1A receptor
      agonist, from saline. Neither fluoxetine, citalopram, nor imipramine generalized
      to the 8-OH-DPAT-induced stimulus cue. However, when administered in addition to
      8-OH-DPAT, both fluoxetine (10 mg/kg) and citalopram (10 mg/kg) lowered the ED50
      for generalization of 8-OH-DPAT from 0.16 mg/kg (8-OH-DPAT by itself) to 0.05
      mg/kg (fluoxetine + 8-OH-DPAT) and 0.06 mg/kg (citalopram + 8-OH-DPAT). Under
      similar conditions, imipramine (1 mg/kg) had no effect on the generalization
      curve for 8-OH-DPAT. The data support the hypothesis that activation of the 5
      HT1A receptor may be relevant to the mechanism of action of serotonin reuptake
      inhibitors.

PMID- 9593592
TI  - Effects of 5-HT1A receptor antagonists on fluoxetine-induced changes in
      extracellular serotonin concentrations in rat frontal cortex.
AB  - Clinical studies in which serotonin specific reuptake inhibitors have been co
      administered with pindolol have demonstrated a shortened time to onset of
      antidepressant activity. This effect has been attributed to the antagonist
      effects of pindolol at the presynaptic 5-HT1A receptor which augments the action
      of the serotonin specific reuptake inhibitors. In the present study, we
      demonstrate that acute fluoxetine-induced increases in extracellular serotonin
      concentrations, as measured by microdialysis in the frontal cortex, can be
      potentiated by 5-HT1A receptor blockade using N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(pyridinyl)cyclohexa necarboxamide (WAY100635), the silent
      and selective 5-HT1A receptor antagonist. WAY100635 at doses as low as 0.03 mg/kg
      s.c. maintained this potentiation effect across a range of fluoxetine doses. In
      addition, using antagonists with different intrinsic agonist activities for the 5
      HT1A receptor, we have determined that only compounds with very low intrinsic
      agonist activity can produce a potentiation of the acute fluoxetine-induced
      increases in extracellular serotonin.

PMID- 9593593
TI  - Chronic naltrexone differentially affects supraspinal delta-opioid receptor
      mediated antinociception.
AB  - The effects of chronic treatment with naltrexone, an opioid receptor antagonist,
      on delta1- and delta2-opioid receptor agonist-induced antinociception and ligand
      binding were investigated in mice. Antinociception by intracerebroventricular
      (i.c.v.) [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II, agonists
      selective for delta1- and delta2-opioid receptors, respectively, was blocked
      following subcutaneous (s.c.) implantation of a naltrexone pellet (7.5 mg) for 7
      days. Removal of the naltrexone pellet was followed 24 h later by a decrease of
      7.5-fold in the ED50 value of [D-Ala2]deltorphin II, but not that of DPDPE. In a
      whole brain homogenate the binding of [3H][D-Ala2]deltorphin II was increased
      twice as much as that of [3H]DPDPE. Chronic naltrexone treatment also produced an
      8.6-fold decrease in the ED50 value of i.c.v. administered morphine. The increase
      in morphine potency was reversed to a control (placebo-treated mice) value by the
      selective delta2-opioid receptor antagonist, naltriben (25 pmol, i.c.v.). Thus,
      chronic naltrexone selectively increases delta2-opioid receptor-mediated
      antinociception, supporting the existence of delta opioid receptor subtypes with
      distinct adaptive characteristics. The data also indicate that delta2-opioid
      receptors are critically involved in the expression of morphine supersensitivity.

PMID- 9593594
TI  - Proconvulsant effects of neurosteroids pregnenolone sulfate and
      dehydroepiandrosterone sulfate in mice.
AB  - We have investigated the effects of chronic treatment with the neurosteroids,
      pregnenolone sulfate and dehydroepiandrosterone sulfate, on the potential
      neurotoxicity in pentylenetetrazol seizure sensitivity test in mice. Four weeks
      of subcutaneous treatment with pregnenolone sulfate and dehydroepiandrosterone
      sulfate, at a dose of 10 mg kg(-1) day(-1), significantly shifted the
      pentylenetetrazol dose-percent convulsions and latency curves to the left, and
      markedly decreased the ED50 of pentylenetetrazol for tonic convulsions,
      indicating the increased sensitivity of mice to seizures. Chronic neurosteroid
      treatment significantly decreased the body weight of the animals. However, acute
      treatment of neurosteroids did not modify the seizure reactivity of mice to
      pentylenetetrazol. Furthermore, the dehydroepiandrosterone sulfate (10 mg kg(-1),
      s.c.)-induced proconvulsant effect was significantly prevented by chronic
      pretreatment with progesterone (5 mg kg(-1), s.c.), a precursor for GABA(A)
      receptor active neurosteroid, allopregnanolone, and dizocilpine (0.1 mg kg(-1),
      i.p.), a non-competitive NMDA receptor antagonist. These results suggest that
      long-term administration of neurosteroids pregnenolone sulfate or
      dehydroepiandrosterone sulfate produces proconvulsant effects.

PMID- 9593595
TI  - Carvedilol inhibits activation of stress-activated protein kinase and reduces
      reperfusion injury in perfused rabbit heart.
AB  - Stress-activated protein kinase (SAPK/JNK) has been implicated in the signaling
      pathway that leads to cell death. Carvedilol, a new vasodilating beta
      adrenoceptor antagonist with potent antioxidant activity, has been shown to
      convey a high degree of cardioprotection in a variety of experimental models of
      myocardial ischemia as well as in patients with congestive heart failure. The
      present study was designed to explore whether the cardioprotective effects of
      carvedilol involve inhibition of SAPK activation. Ex vivo ischemia (30 min)
      reperfusion (60-120 min) of the rabbit heart resulted in 67% reduction of
      pressure-rate product, 45% necrosis of left ventricular tissue and 62% loss of
      myocardial creatine kinase (P < 0.01 vs. basal). SAPK levels in the perfused
      hearts increased markedly following reperfusion (5.6-fold increase, P < 0.01 vs.
      basal). Carvedilol, at 10 microM, administered at time of reperfusion, enhanced
      recovery of pressure-rate product by 61%, reduced necrotic size by 65% and
      decreased myocardial creatine kinase loss by 62% (P < 0.01 vs. vehicle).
      Carvedilol also inhibited reperfusion-induced activation of SAPK by 61% (P<0.01
      vs. vehicle). Carvedilol, at 1 microM, displayed a trend of cardioprotection and
      inhibition of SAPK activation. Our results suggest that SAPK may play a role in
      ischemia/reperfusion-induced cardiac injury and inhibition of SAPK activation by
      carvedilol may contribute to its cardioprotective effects.

PMID- 9593596
TI  - Melatonin mediates two distinct responses in vascular smooth muscle.
AB  - The pineal hormone melatonin was found to produce two distinct contractile
      responses in vascular smooth muscle. In isolated rat caudal artery segments,
      denuded of endothelium, melatonin (10(-10)-10(-7) M) potentiated phenylephrine
      induced contractions in a concentration-dependent manner. At higher melatonin
      concentrations (10(-7)-10(-5) M), however, the potentiating effect was
      attenuated. In the presence of the melatonin MT2 receptor antagonist, 4-phenyl-2
      acetamidotetraline (4P-ADOT), the attenuated constrictor responses were
      selectively enhanced. These results are consistent with the hypothesis that
      melatonin activates two receptor subtypes in vascular smooth muscle; MT2
      receptors may induce relaxation, while a second receptor subtype mediates
      vasoconstriction.

PMID- 9593597
TI  - The influence of age on isolated tracheal responsiveness to spasmogens.
AB  - The influence of animal age was examined on the responses of guinea-pig (birth
      156 weeks) and rat (4-136 weeks) isolated tracheal tissue to the spasmogens
      histamine, 5-hydroxytryptamine (5-HT) and potassium ions (K+) using functional
      and biochemical techniques. Over the ages birth-12 weeks in the guinea-pig, K+
      potency decreased 1.5 fold whereas histamine potency increased 2-fold between the
      ages of birth-2 weeks and then declined to original levels by age 20 weeks. 5-HT
      potency declined over the entire age range examined, resulting in a 25.1 fold
      decrease between the ages of 1 and 156 weeks. In the rat, 5-HT potency remained
      unchanged and a small but progressive increase in K+ potency was observed with
      respect to animal age. Significant age-related changes in inositol phosphate
      accumulation were observed in both unstimulated and histamine-stimulated isolated
      guinea-pig tracheal smooth muscle which did not correlate with the functional
      changes observed in response to spasmogenic stimulation. The results describe
      disparate age-related changes between two species of different spasmogenic
      agonists with the majority of age-related changes occurring during the maturation
      phase of growth of the guinea-pig.

PMID- 9593598
TI  - Comparison between the effects of sigma receptor ligand JO 1784 and neuropeptide
      Y on immune functions.
AB  - Recent evidence suggests that sigma receptor ligands and neuropeptide Y may act
      through the same pathways to modulate centrally mediated immune function. The
      present study demonstrated that both the sigma receptor ligand igmesine: (+)-N
      cyclopropylmethy-N-methyl-1, 4-diphenyl-1-yl-but-3-en-1-ylamine, hydrochloride
      (JO 1784) (10(-7) and 10(-5) M) and neuropeptide Y (10(-9) and 10(-7) M) in vitro
      significantly reduced neutrophil phagocytosis and decreased mitogen stimulated
      lymphocyte proliferation. By contrast, central administration of JO 1784 (0.5 and
      5 microg/5 microl) significantly reduced the activity of neutrophil phagocytosis,
      but enhanced lymphocyte proliferation without changing the serum concentration of
      corticosterone. Neuropeptide Y (10(-9) and 10(-7) M), following
      intracerebroventricular infusion, also decreased the neutrophil response, but
      significantly raised the corticosterone concentration. These results indicate
      that different mechanisms (involving various neurotransmitters and their
      receptors, changes in the activity of the hypothalamic-pituitary-adrenal axis, or
      sigma receptor subtypes) may be involved in the central effects of JO 1784 and
      neuropeptide Y.

PMID- 9593599
TI  - Effect of aescine on hypoxia-induced neutrophil adherence to umbilical vein
      endothelium.
AB  - Although venous stasis due to blood stagnation in lower limbs has been recognised
      as an important etiological factor for the development of varicose veins, the
      mechanism linking this ischemic situation to the modifications of the venous wall
      in varicose veins is still unclear. There is evidence that the activation of the
      endothelium during blood stasis and its subsequent cascade of interactions with
      other cell types could alter the structure of the vein wall and could possibly be
      at the origin of the disease. While phlebotonic drugs are often used to improve
      symptoms in chronic venous insufficiency, their precise mechanism of action is
      not well understood. We now tested aescine (Reparil i.v. form) in an ex vivo
      model which mimics this situation, i.e., perfused human umbilical vein exposed to
      hypoxic conditions. To study the effect of aescine on neutrophil activation and
      adhesion to the endothelium, human umbilical veins were incubated under hypoxic
      conditions with or without aescine and the interactions between the endothelium
      and neutrophil-like cells, HL60, were investigated. We observed that a large
      number of HL60 became adherent to the endothelium of veins after 2 h hypoxia and
      that these adherent HL60 were activated: they released high amounts of superoxide
      anion and of leukotriene B4. Aescine (250 ng/ml or 0.22 microM) was shown to
      markedly inhibit HL60 adherence to hypoxic endothelium. By decreasing the number
      of adherent HL60, aescine also decreased the subsequent production of superoxide
      anion and of leukotriene B4. Scanning electron microscopy confirmed the increased
      HL60 adherence to the endothelium, as well as the inhibitory effect of aescine.
      These results support results of in vitro studies on isolated endothelial cells
      in which aescine was shown to inhibit the hypoxia-induced activation of
      endothelial cells and the subsequent increased adherence of neutrophils. In vivo,
      the activated and infiltrated leukocytes release free radicals, chemotactic
      molecules such as leukotriene B4 and proteases which then can degrade the
      extracellular matrix. These processes could contribute to alterations of the
      venous wall similar to those observed in varicose veins. By maintaining an intact
      endothelium during in vivo blood stasis in the lower limbs and preventing
      neutrophil recruitment, adherence and activation, aescine could prevent the
      resulting alterations of the venous wall. These results could explain at least in
      part the potential benefit of the drug in the prevention of venous insufficiency.

PMID- 9593600
TI  - Identification of [3H]P1075 binding sites and P1075-activated K+ currents in
      ovine choroid plexus cells.
AB  - This study examined the pharmacological characteristics of binding sites for the
      potent K+ channel opener [3H]P1075, as well as the functional effects of P1075 on
      ionic currents and membrane potential, in ovine choroid plexus (OCP) cells.
      [3H]P1075 bound to OCP cells with a Kd of 26 +/- 4 nM and a Bmax of 10400 +/- 480
      sites/cell. Labelled sites were stereoselective and inhibited by potassium
      channel openers with a rank order of potency: P1075 > BMS-182264, ((4
      [[9cyanoimino)[(1,2,2-trimethylpropyl)amino]-methyl]amino]benz onitrile) >
      pinacidil >> nicorandil > diazoxide. The K(ATP) channel antagonist glyburide
      inhibited [3H]P1075 binding with a Ki of 2 microM. The presence of K(ATP)
      channels on OCP cells was examined by patch clamp and fluorescent (membrane
      potential sensitive dye) techniques. In some cells, P1075 activated an outward
      potassium current which was blocked by glyburide. P1075 produced a glyburide
      sensitive, concentration-dependent, hyperpolarization of OCP cells. Levcromakalim
      hyperpolarized more strongly than its 3R,4S enantiomer, BRL 38226 ((3R-trans)-3,4
      dihydro-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)- 2H-1-benzopyran-6
      carbonitrile) indicating a stereoselective interaction. These data indicate that
      epithelial OCP cells contain glyburide-sensitive K(ATP) channels.

PMID- 9593601
TI  - A selective analog for the somatostatin sst1-receptor subtype expressed by human
      tumors.
AB  - Somatostatin mediates its actions through five different somatostatin receptor
      subtypes, sst1-sst5. Recently, the somatostatin analogs des-AA1,2,5-[D-Trp8,
      IAmp9]somatostatin and des-AA1,5-[Tyr2, D-Trp8, IAmp9]somatostatin were
      synthesized and shown to be sst1-selective when tested in COS-7 cells transfected
      with each of the sst subtypes. In the present study, we tested the binding
      affinity and specificity of the iodinatable analog in primary human tumors
      expressing various sst subtypes, selected on the basis of in situ hybridization
      experiments. Des-AA1,5-[Tyr2, D-Trp8, IAmp9]somatostatin was found to have a high
      affinity, comparable to that of the natural somatostatin-28, for sst1-expressing
      tumors such as prostate cancers. However, it had no affinity for tumors
      expressing the sst2, sst3, or sst5 subtypes. For comparison, the somatostatin
      analogs octreotide or Tyr3-octreotide have no affinity for sst1-expressing
      tumors, but high affinity for sst2- and sst5-expressing tumors and intermediate
      affinity for sst3-expressing tumors. These data represent the first
      characterization of a sst1-selective analog in human tumors; it may be of
      potential use in the therapy of sst1-expressing tumors as an antiproliferative
      agent, as well as providing a lead compound for the development of more potent
      sst1-selective radioligands for in vivo tumor scintigraphy.

PMID- 9593602
TI  - Unique binding pocket for KW-4679 in the histamine H1 receptor.
AB  - The histamine H1 receptor has an aspartate (Asp) residue in transmembrane helix 3
      (TM3), which is well-conserved among biogenic amine receptors. The Asp residue is
      one of the most crucial amino acids for ligand binding. The tested histamine H1
      receptor antagonists with tri- and tetracyclic structures were not selective for
      histamine H1 receptors and showed affinity for several other biogenic amine
      receptors. In contrast, KW-4679 ((Z)-11-[3-(dimethylamino)propylidene]-6,11
      dihydrodibenz[b, e]oxepin-2-acetic acid hydrochloride), a tricyclic compound, was
      a selective histamine H1 receptor antagonist. [3H]KW-4679 had high affinity (Kd
      value of 2.5 +/- 0.12 nM) for wild-type human histamine H1 receptors. In the
      [3H]KW-4679 binding assay, replacement of Asp107 by alanine by site-directed
      mutagenesis greatly reduced the affinities (280-2100-fold) of tri- and
      tetracyclic compounds, whereas this mutation led to a comparatively small
      reduction (14-fold) in KW-4679 affinity. These results demonstrate that the
      tested tri- and tetracyclic histamine H1 receptor antagonists which have a tight
      interaction with the Asp residue are not selective for the histamine H1 receptor.
      Furthermore, the high selectivity of KW-4679 might be explained by a unique
      binding pocket, which consists of the Asp residue and other acceptor sites, in
      the histamine H1 receptor.

PMID- 9593603
TI  - Emergency contraception--cost-accounting.

PMID- 9593604
TI  - Emergency postcoital contraception.
AB  - Of the estimated 3.5 million unintended pregnancies that occur each year in the
      United States, some 1.7 million are thought to be the result of contraceptive
      failure. The extremely high numbers of unintended pregnancies not only in the
      United States but also worldwide indicates that emergency contraception remains
      an important but underused method of pregnancy prevention. Emergency postcoital
      contraception via mechanical or pharmacological means inhibits fertilization
      and/or implantation from unprotected sexual intercourse. Although emergency
      contraception has been used primarily in victims of sexual assault, it offers a
      low-cost, highly effective method to reduce the incidence of unintended
      pregnancy. Emergency contraception decreases the costs and emotional and physical
      risks to women who have had unprotected intercourse. Emergency contraception also
      increases the latitude women have to make reproductive decisions by offering an
      alternative to abortion and childbearing. The heart of the problem with emergency
      contraception is not the failure rate or side effects of specific methods but the
      fact that so few women and adolescents who have had unprotected intercourse know
      the option exists, and their providers may be reluctant to prescribe the method.

PMID- 9593605
TI  - Human chorionic gonadotropin stimulation to assess for ovarian hyperandrogenism.
AB  - STUDY OBJECTIVE: To determine whether human chorionic gonadotropin (hCG)
      stimulation elicits an exaggerated 17-hydroxyprogesterone (17-OHP) response in
      patients with functional ovarian hyperandrogenism. METHODS: In this clinical
      study, healthy volunteers and hyperandrogenic patients in an outpatient General
      Clinical Research Center (GCRC) setting were studied. Five adolescent girls with
      functional ovarian hyperandrogenism were studied. Six healthy women with regular
      menstrual cycles volunteered for this study. Steroid hormone responses to hCG
      stimulation were measured before and 30, 240, and 300 minutes after hCG
      injection. Congenital adrenal hyperplasia was excluded through ACTH stimulation
      testing and molecular genetic analysis. MAIN OUTCOME MEASURE: 17-OHP responses.
      RESULTS: Mean basal 17-OHP concentrations were greater in the hyperandrogenic
      patients, 110.4+/-41.2 ng/dL versus 61.8+/-28.6 ng/dL. After hCG stimulation, 17
      hydroxyprogesterone concentrations significantly increased in the patients and
      were unchanged in the healthy controls. CONCLUSION: hCG stimulation elicited
      greater 17-hydroxyprogesterone responses in adolescent girls with functional
      ovarian hyperandrogenism compared with healthy controls. hCG stimulation may be
      helpful to confirm ovarian hyperandrogenism.

PMID- 9593606
TI  - Employment and health-risk behaviors among pregnant adolescents.
AB  - STUDY OBJECTIVE: To compare health-risk behaviors, maternal, and neonatal
      outcomes of pregnant adolescents less than 18 years old who reported employment
      more than 15 hours per week with those who did not report working. We
      hypothesized that working teens compared with nonworking adolescents would report
      higher rates of health-risk behaviors. METHODS: A structured interview was
      conducted at the first prenatal visit and the medical chart was reviewed to
      extract pregnancy (pregnancy-induced hypertension, preterm labor with
      hospitalization, and preterm delivery) and neonatal outcomes (low birthweight,
      small for gestational age, and admission to the neonatal intensive care unit).
      The study was conducted at an outpatient maternal and child health clinic at a
      university teaching hospital. A total of 384 white (n=111), African American
      (n=151), and Mexican American (n=99) adolescents, aged 12 to 17 years, who
      initiated care between January 2, 1992, and December 31, 1994, and delivered an
      infant at our institution were consecutively sampled. A structured interview
      assessed various health-risk behaviors including age at first intercourse,
      substance use (tobacco, alcohol, and other illicit drug use), and number of
      sexual partners. Medical records were reviewed to obtain information on pregnancy
      complications (pregnancy-induced hypertension, preterm delivery, and preterm
      labor with hospitalization) and negative birth outcomes (infant birthweight and
      neonatal intensive care admission). RESULTS: Controlling for chronological age,
      logistic regression analyses found that adolescents reporting employment at their
      first prenatal visit (n=40) compared with those not employed at this visit
      (n=331) were more likely to be characterized by school enrollment, higher
      economic status, partner employment, partner alcohol use, and a longer
      relationship with the father of their baby. Multivariate logistic regression
      found that employed females were 4.6 times more likely to deliver a small-for
      gestational-age infant. CONCLUSIONS: Employment reported at the time of the first
      prenatal visit does not appear to be associated with an increase in health-risk
      behaviors or obstetric complications, but a relationship between working more
      than 15 hours and small-for-gestational-age delivery was detected.

PMID- 9593607
TI  - Ovarian cysts in children and adolescents: their occurrence, behavior, and
      management.
AB  - STUDY OBJECTIVE: To evaluate the characteristics and symptoms of ovarian cysts,
      their connection with the methods of treatment, and the effectiveness of the
      therapy. METHODS: A retrospective analysis of data on girls with ovarian cysts
      was performed at a university clinic. Participants included 119 girls in whom 144
      ovarian cysts were found by ultrasound examination performed either routinely or
      for a specific purpose. One group of patients received gestogen to facilitate
      resolution of the cyst and as treatment of menstrual disorder. Others received
      clomiphene citrate exclusively as therapy for menstrual irregularity. Aside from
      this, patients were treated by surgical intervention, or only follow-up
      sonography was performed. The site, number, size, and type of the cysts were
      examined. The indications for ultrasonography and the effectiveness of the
      treatment were analyzed. RESULTS: The ovarian cysts were mostly unilateral,
      unilocular, and simple, with the size varying between 3 cm and 5 cm in diameter
      in 90 cases, more than 5 cm in 41 cases, and less than 3 cm in 13 cases. A number
      of cysts were found incidentally on ultrasound. Girls were scanned most often
      because of irregular bleeding (80 cases). Hormonal treatment was given in 105
      cases, whereas in 35 cases only follow-up sonography was performed. Cysts
      resolved spontaneously in 4.5 weeks on average, or in 3 weeks after hormonal
      treatment. Surgical therapy was necessary for nine patients. The indication for
      surgery was the detection of complex cysts indicative of dermoid type, size of
      the cysts, severe pelvic pain, or failure of the cyst to resolve or decrease in
      size spontaneously or in response to treatment as determined by follow-up
      sonography. All of the cysts were benign on pathological evaluation. CONCLUSION:
      Most ovarian cysts in girls could be managed conservatively, even the larger ones
      greater than 5 cm in diameter. Only exceptional cases required surgical therapy.
      Hormonal treatment shortened the duration of the cysts somewhat, but not
      significantly, and thus was useful mainly in the treatment of concomitant
      menstrual disorders.

PMID- 9593608
TI  - XY gonadal dysgenesis in an adolescent with chronic renal failure: a case of
      Frasier syndrome.
AB  - STUDY OBJECTIVE: To report a case of XY gonadal dysgenesis in an adolescent with
      renal failure and to review the literature on this association. METHODS: In this
      case report from the Tertiary Care University Medical Center, a 16-year-old
      female with chronic renal failure presenting with primary amenorrhea was studied.
      Interventions included laparotomy with bilateral gonadectomy and hormone
      replacement therapy. MAIN OUTCOME MEASURES: Karyotype, gonadal histology.
      RESULTS: Diagnosis of gonadal dysgenesis. Presence of a gonadoblastoma.
      CONCLUSIONS: Gonadal dysgenesis should be considered in any female adolescent
      with renal disease presenting with pubertal delay or primary amenorrhea.

PMID- 9593609
TI  - Secondary amenorrhea with severe intrauterine adhesions and chronic uterine
      torsion after Cesarean section in a teenage girl.
AB  - This is a case of a 19-year-old patient who developed secondary amenorrhea after
      Cesarean section and severe postpartum hemorrhage. The pelvic examination
      revealed narrowing of the upper vagina and inaccessible cervix. Laparotomy
      revealed a dextrorotated uterus with massive intrauterine adhesions. All
      adhesions were excised with reconstruction of normal uterine anatomy. The patient
      regained normal menstrual cycles. There was no evidence of any endocrinopathies.
      According to a 10-year MEDLINE search of the literature, chronic torsion of the
      uterus after Cesarean section has not been previously described.

PMID- 9593610
TI  - Opinions in Pediatric and Adolescent Gynecology. Treatment of the high-grade
      squamous intraepithelial lesion of the cervix in adolescents: loop electrical
      excision procedure or cryotherapy.

PMID- 9593611
TI  - Persistent Mullerian duct syndrome.

PMID- 9593612
TI  - Management quandary. Varicella.

PMID- 9593613
TI  - First-pass versus second-pass parsing processes in a Wernicke's and a Broca's
      aphasic: electrophysiological evidence for a double dissociation.
AB  - The present paper is a first attempt to integrate the classical brain lesion
      behavioral impairment approach of functional neuroanatomy and the
      electrophysiological brain mapping approach in the domain of syntactic
      processing. In a group of normal age-matched controls we identified three
      electrophysiological components previously observed in correlation with language
      comprehension processes: an early left anterior negativity normally seen in
      correlation with syntactic first-pass parsing processes (ELAN), a centroparietal
      negativity seen in correlation with processes of lexical-semantic integration
      (N400), and a late centroparietal positivity observed in correlation with
      secondary syntactic processes of reanalysis and repair (P600). The early left
      anterior negativity was absent in a patient with an extended lesion in the
      anterior part of the left hemisphere sparing the temporal lobe, although the late
      centroparietal positivity and the centroparietal N400 were present. In a patient
      with a left temporal-parietal lesion the early left anterior negativity was found
      to be present, whereas the N400 component was absent. These findings suggest that
      first-pass parsing and secondary processes are subserved by distinct brain
      systems.

PMID- 9593614
TI  - Error-revision in the spontaneous speech of apraxic speakers.
AB  - Spontaneous speech samples from four men diagnosed with apraxia of speech were
      transcribed to examine the ways in which they attempted to repair their speech
      errors. The study sought evidence for the presence of production or perceptual
      constraints in error revision and for the presence of a functional
      prearticulatory monitor. Three judges independently evaluated the transcriptions
      and audiotapes to identify instances in which speakers revised speech errors.
      They then coded the nature of the relationship between the error and the
      revision. In previous reports, the form of error repairs among normal speakers
      has been attributed to perceptual constraints, that is, determined by the needs
      of the listener. Results of the present study suggest that the form of some error
      repairs among these speakers with apraxia of speech is not in the service of the
      listener; rather, it conforms with production constraints. It may be argued that
      some forms of error repair evidenced by these speakers, such as the prosodic
      marking of phonetic errors and prosodic marking in the temporal domain (syllable
      segregation), may actually serve to exacerbate the listener's task of message
      decoding. In addition, these speakers offered little evidence of an efficient
      prearticulatory monitor. The time delays between interrupting the flow of speech
      in recognition of an error and the initiation of a revision suggest an impaired
      ability to plan revisions prior to the production of the error.

PMID- 9593615
TI  - Task demands and sentence comprehension in patients with dementia of the
      Alzheimer's type.
AB  - Patients with dementia of the Alzheimer's type (DAT) and matched normal controls
      were given three tests of syntactic comprehension in which nonlinguistic visual
      and memory task demands were varied. In all tasks, subjects were presented spoken
      semantically reversible sentences with a variety of syntactic structures and
      required to match the sentence to a picture. In the first experiment, subjects
      matched the spoken sentence to one of two pictures that appeared either before or
      immediately following the presentation of the sentence. The target picture
      depicted the spoken sentence correctly and the foil depicted the reversed
      thematic roles to those in the sentence (i.e., it was a syntactic foil). The
      second experiment employed a sentence video-verification task in which subjects
      were required to determine if the spoken sentence matched a videotaped depiction
      of the action in the sentence or a syntactic foil. In the third experiment, in
      different conditions, subjects were required to determine whether the spoken
      sentence matched a single picture or to choose the picture that matched the
      sentence from an array of two or three pictures. In this experiment, both lexical
      and syntactic foils were used. In all tasks, DAT patients were affected by the
      number of propositions in the presented sentence, but not by the syntactic
      complexity of the sentence. Control subjects also were unaffected by the
      syntactic complexity of the sentence; the number-of-proposition effect was
      present in some experiments in the control population. Comparison of performance
      across the one-, two-, and three-picture versions of the task showed that the
      magnitude of the effect of number of propositions increased as the number of
      pictures in the array increased. In addition, analysis of the data from each of
      the tasks separately showed that the effect of number of propositions only
      occurred when subjects were attempting to match the target to a syntactic foil
      (one-picture version) or to choose between the target and a syntactic foil (two-
      and three-picture versions). The results support the view that patients with DAT
      do not have disturbances affecting syntactic processing. In addition, they
      suggest that the effect of number of propositions arises at a stage of analysis
      that is partially separate from assigning sentence meaning, such as in holding a
      representation of the sentence in memory until the pictures can be analyzed and
      encoded and/or in comparing the results of the picture analysis with a stored
      representation of the sentence meaning.

PMID- 9593616
TI  - Comparison of graphic symbol learning in individuals with aphasia and right
      hemisphere brain damage.
AB  - This study compared the differences in performance on recognition of graphic
      symbols across time by individuals with aphasia, individuals with right
      hemisphere brain damage, and neurologically normal adults. The subjects, seen
      individually, learned 40 Blissymbols. The symbols were selected so that the
      effects of symbol translucency and complexity on the recognition of graphic
      symbols could be examined. A paired-associate learning paradigm was used to teach
      the symbol-referent pairs to subjects. The results indicated that individuals
      with aphasia and neurologically normal adults do not differ significantly in
      recognition of graphic symbols. However, individuals with right-hemisphere damage
      recognized fewer symbols compared to individuals with aphasia and normal adults,
      suggesting that they have difficulty in associative learning of graphic symbols.
      Additionally, translucency was found to be a potent factor in the recognition of
      Blissymbols by all groups. The finding that individuals with severe chronic
      aphasia can learn and retain graphic symbols has significant clinical
      implications for aphasia rehabilitation.

PMID- 9593617
TI  - Brain organization of language after early unilateral lesion: a PET study.
AB  - Neuropsychological studies suggest that good long-term language outcome is
      possible following extensive early left-hemisphere damage. We explored the brain
      organization for language in children with early unilateral lesion, using [15O]
      water PET. In 12 patients with left lesion (LL) and 9 patients with right lesion
      (RL), cerebral blood flow changes during listening to sentences and repetition
      were studied. A rightward shift of language activations in the LL group was found
      in perisylvian areas and multiple other, mostly temporo-parietal, regions. The
      hypothesis of intrahemispheric reorganization in the LL group found only limited
      support. The number of activated regions was overall greater in the RL group.
      Unexpected findings included a stronger subcortical and cerebellar language
      involvement in the RL group. We suggest that (a) early left lesion is associated
      with enhanced language participation of the right hemisphere in and beyond the
      classical language areas, and (b) postlesional effects are in part additive
      (recruitment of noncanonical areas), in part subtractive (functional depression
      in areas normally involved in language).

PMID- 9593618
TI  - Murtagh's case of selective language deficit in a bilingual.

PMID- 9593620
TI  - The evolution of communication: An ethological exploration 
AB  - Copyright

PMID- 9593619
TI  - Features resembling Tourette's syndrome in developmental stutterers.
AB  - Developmental stuttering (DS) may be related to the extrapyramidal motor system
      and shares many clinical similarities with Tourette's syndrome (TS), which is
      widely believed to be associated with extrapyramidal dysfunction. Twenty-two
      stutterers were examined for neuropsychiatric features commonly seen in TS,
      including tics, obsessive-compulsive behaviors (OCB), and attention deficit
      disorders. Eleven stutterers displayed motor tics, and symptoms of OCB were
      observed at rates similar to those seen in persons with TS. Few stutterers
      demonstrated significant attentional deficits. Findings are consistent with
      models suggesting extrapyramidal involvement in DS and raise the possibility that
      DS and TS are pathogenetically related.

PMID- 9593622
TI  - Association between renal effects and cadmium exposure in cadmium-nonpolluted
      area in Japan.
AB  - Renal effects of cadmium exposure in people living in a cadmium-nonpolluted area
      in Japan were investigated. The population consisted of 1501 inhabitants (558 men
      and 743 women) over 50 years of age. Urinary cadmium was employed as an indicator
      of internal dose, and total urinary protein, beta 2-microglobulin, and N-acetyl
      beta-glucosaminidase were used as indicators of renal dysfunction. Multiple
      regression analysis and a logistic regression analysis were performed to study
      the relationship between urinary cadmium excretion and these indicators of renal
      dysfunction. In both procedures, urinary cadmium concentrations were
      significantly associated with indicators of renal dysfunction. These results
      suggest the existence of renal dysfunction induced by exposure to environmental
      cadmium in a cadmium-nonpolluted area in Japan.

PMID- 9593623
TI  - Does weather confound or modify the association of particulate air pollution with
      mortality? An analysis of the Philadelphia data, 1973-1980.
AB  - Because weather has the potential to confound or modify the pollution-mortality
      relationship, researchers have developed several approaches for controlling it in
      estimating the independent effect of air pollution on mortality. This report
      considers the consequences of using alternative approaches to controlling for
      weather and explores modification of air pollution effects by weather, as weather
      patterns could plausibly alter air pollution's effect on health. We analyzed 1973
      1980 total mortality data for Philadelphia using four weather models and compared
      estimates of the effects of TSP and SO2 on mortality using a Poisson regression
      model. Two synoptic categories developed by Kalkstein were selected--the Temporal
      Synoptic Index (TSI) and the Spatial Synoptic Classification (SSC)--and compared
      with (1) descriptive models developed by Schwartz and Dockery (S-D); and (2)
      LOESS, a non-parametric function of the previous day's temperature and dew point.
      We considered model fit using Akaike's Information Criterion (AIC) and changes in
      the estimated effects of TSP and SO2. In the full-year analysis, S-D is better
      than LOESS at predicting mortality, and S-D and LOESS are better than TSI, as
      measured by AIC. When TSP or SO2 was fit alone, the results were qualitatively
      similar, regardless of how weather was controlled; when TSP and SO2 were fit
      simultaneously, the S-D and LOESS models give qualitatively different results
      than TSI, which attributes more of the pollution effect to SO2 than to TSP. Model
      fit is substantially poorer with TSI. This pattern was repeated in analyses of
      summer and winter months, which included SSC. In summary, using synoptic weather
      categories in regression models does not meaningfully change the association
      between mortality and air pollution indexes. We also found little evidence that
      weather conditions modified the effect of pollution, regardless of the approach
      used to represent weather.

PMID- 9593624
TI  - Methylmercury and inorganic mercury in serum--correlation to fish consumption and
      dental amalgam in a cohort of women born in 1922.
AB  - Methylmercury in serum (S-MeHg) was assessed from serum concentrations of total
      (S-TotHg) and inorganic mercury (S-InoHg), determined by cold vapor-atomic
      absorption spectrometry. The samples were collected from 135 women on two
      occasions, in 1968-1969 and 1980-1981. In a subgroup of 29 women, an association
      was found between S-MeHg and the amount of fish consumed in 1968-1969 (r = 0.38,
      P = 0.04). The association was stronger (r = 0.50; P = 0.006) when the
      individuals' mean S-MeHg from 1968-1969 and 1980-1981 were plotted vs fish
      consumption 1968-1969. In the group, as a whole, there was an association between
      S-InoHg and number of dental amalgam surfaces, in both 1968-1969 (r = 0.48, P =
      0.0001) and 1980-1981 (r = 0.57, P < 0.0001). The S-InoHg increased by
      approximately 0.1 nmol/L per amalgam tooth surface, corresponding to an uptake of
      approximately 0.2 microgram/day per amalgam surface, but with considerable
      interindividual differences. The levels were lower in 1980-1981 than in 1968-1969
      for both MeHg and InoHg. The medians and ranges (nmol/L) were for MeHg 1968-1969:
      3.6 (0.3-11.9); MeHg 1980-1981, 2.0 (-0.4-8.7); InoHg 1968-1969, 3.3 (0.7-11.8);
      InoHg 1980-1981, 1.7 (0.1-11.8); TotHg 1968-1969, 7.2 (1.9-18.8); and TotHg 1980
      1981, 3.9 (1.0-14.2). The decrease in S-MeHg is probably due to a decreased
      consumption of MeHg via contaminated fish. The decrease in S-InoHg may reflect a
      decrease in environmental exposure, but the possibility of contamination of the
      1968-1969 samples at sampling and/or storage cannot be excluded.

PMID- 9593625
TI  - Fishing, consumption, and risk perception in fisherfolk along an east coast
      estuary.
AB  - Increasingly public and governmental agencies are concerned about the safety of
      fish and shellfish that recreational fishermen consume. Fishing behavior,
      consumption patterns, and risk perceptions were examined for people flashing and
      crabbing in Barnegat Bay, NJ. Women fished in significantly larger groups than
      men, and their groups included more children. Subjects fished an average of seven
      times per month and crabbed three times per month; they caught fish on most
      outings, and 80% ate their catch. Subjects consumed fish an average of five times
      a month, eating just under 10 oz (ca. 280 g) per meal. Only 25% of the fish
      consumed by women, and 49% of the fish consumed by men, are self-caught. Nearly
      90% of the people believe the fish and crabs from Barnegat Bay are safe to eat,
      although about 40% have heard some warnings about their safety. Most people heard
      about advisories from newspapers or television. Most subjects believe that
      saltwater fish are safer than freshwater fish and that fish they catch themselves
      or buy in a bay store are safer than those from a supermarket. People generally
      do not have a clear understanding of the relationship between contaminants and
      fish size or trophic level, suggesting an avenue for risk reduction.

PMID- 9593626
TI  - Temporal trends in metal levels in eggs of the endangered roseate tern (Sterna
      dougallii) in New York.
AB  - Female birds sequester certain organic and inorganic compounds in their eggs
      which have been widely used as a bioindicator for examining the body burdens of
      contaminants and therefore the temporal and spatial trends of the contaminants in
      the environment. The same analyses can also reflect the status or vulnerability
      of the indicator species. Extensive bridge de-leading activities in the New York
      Bight (Cape May to Montauk) in the early 1990s coincided with a long-term study
      of the endangered roseate tern (Sterna dougallii) on Long Island, New York,
      affording the opportunity to test the utility of such fish-eating species as
      bioindicators of lead contamination, as well as the potential impact on the bird
      population itself. In this paper we test the null hypothesis that there were no
      temporal trends between 1989 and 1994 in metal levels in eggs of roseate terns
      nesting at Cedar Beach, Long Island, where the birds have been declining since
      the late 1980s. We report levels and trends for cadmium, chromium, manganese,
      mercury, and selenium as well as lead in abandoned eggs collected each year.
      There were significant interyear differences for all metals, with 1990 to 1992
      generally having higher levels than 1989 and 1994. The yearly differences were
      particularly prominent for lead, where the 10-fold increase may have been
      partially due to the increased removal of leaded paint from bridges in the early
      1990s, leading to increased lead in the aquatic environment. Cadmium and chromium
      are also released during de-leading. The causes for the higher levels in the
      other metals in the early 1990s are unclear. Metal levels in roseate tern eggs
      are several times higher than the median reported for most birds, and the
      possible impact on the population requires study.

PMID- 9593627
TI  - An assay system for detecting environmental toxicants with cultured cladoceran
      eggs in vitro: malformations induced by ethylenethiourea.
AB  - An in vitro assay system using cladoceran eggs was developed for the detection of
      toxic compounds in the aquatic environment. Parthenogenetic eggs of Daphnia magna
      were removed from the brood chambers of female adults and cultured individually
      in 96-well microtiter plates with Elendt M7 medium at 23 degrees C. Embryonic
      development proceeded completely in vitro with more than 95% hatchability. Egg
      development time in vitro was 2 days, which was almost equal to that in the brood
      chamber of the mother. Ethylenethiourea, a compound teratogenic to mammals, was
      investigated for toxicity to development of eggs. Isolated eggs were cultured in
      the presence of ethylenethiourea during the period of embryonic development for 3
      days. Treatment with ethylenethiourea induced morphological abnormalities in the
      cladoceran carapace. Parthenogenetic eggs of Cladocera are genotypically
      identical, which makes them useful biological materials for a toxicity test on
      aquatic pollutants.

PMID- 9593628
TI  - Effect of the delta-aminolevulinate dehydratase polymorphism on the accumulation
      of lead in bone and blood in lead smelter workers.
AB  - Lead inhibition of the zinc metalloenzyme delta-aminolevulinate dehydratase
      (ALAD) is one of the most sensitive indicators of blood lead levels. ALAD is
      polymorphic, with about 20% of Caucasians expressing the rarer ALAD2 allele.
      Previous studies indicated that this polymorphism may be a genetic factor in lead
      transport, metabolism, and/or distribution. Whole blood lead, serum lead, and
      ALAD genotype were determined for 381 lead smelter workers, including 70 workers
      expressing the ALAD2 allele, whose blood lead elevations were observed for more
      than 20 years of employment. The same employees demonstrated higher serum lead
      levels. Using a cumulative blood lead index (CBLI) for each worker, based on
      individual blood lead histories, and in vivo X-ray fluorescence measurements of
      bone lead to estimate total lead body burden, the slopes of linear relations of
      bone lead to CBLI were greater for workers homoallelic for ALAD1, indicating more
      efficient uptake of lead from blood into bone. This effect was most significant
      in calcaneus bone and for workers hired since 1977 [ALAD1-1: 0.0528 +/- 0.0028
      and ALAD1-2 or 2-2: 0.0355 +/- 0.0031 (P < 0.001)]. Decreased transfer of blood
      lead into bone in individuals expressing the ALAD2 allele contrasted with
      increased blood lead. Thus the ALAD genotype affected lead metabolism and
      potentially modified lead delivery to target organs including the brain; however,
      the ALAD genotype did not significantly affect the net accumulation of lead in
      bone.

PMID- 9593629
TI  - Elevated blood lead levels from exposure via a radiator workshop.
AB  - Elevated lead levels were discovered in blood samples collected from family
      members where both the father and the mother worked in a radiator repair
      workshop. The father and mother were found to have blood lead levels of 2.0 and
      0.5 mumol/L (41.7 and 10.4 micrograms/dL), respectively. The father's blood lead
      level was just below the Canadian occupational health and safety intervention
      level (2.5 mumol/L or 52.1 micrograms/dL). The two children had blood lead levels
      of 1.0 and 0.8 mumol/L (20.8 and 16.7 micrograms/dL), both of which are in excess
      of the recommended guideline for intervention in the case of children (0.5
      mumol/L or 10.4 micrograms/dL). The exposure of the two children was possibly due
      to a combination of pathways including exposure at the workshop itself during
      visits and also the transportation of lead-containing dust to the home
      environment.

PMID- 9593630
TI  - First International Conference on the History of Occupational and Environmental
      Prevention
AB  - Copyright

PMID- 9593631
TI  - In memoriam. ELAINE RUTH BERMAN (1923-1997) 

PMID- 9593632
TI  - Effects of synthetic inhibitor of metalloproteinase and cyclosporin A on corneal
      haze after excimer laser photorefractive keratectomy in rabbits.
AB  - To evaluate the effects of synthetic inhibitor of metalloproteinase (SIMP) and
      cyclosporin A (CsA) on corneal haze after excimer laser photorefractive
      keratectomy (PRK) in rabbits, PRK was performed on 60 rabbits. They were
      randomized to one of four groups: group A which received topical SIMP, group B
      which received topical CsA, group C which received both SIMP and CsA, and group D
      which received vehicles. Another 16 rabbits did not undergo PRK and were
      randomized to one of four groups: group E which received topical SIMP, group F
      which received topical CsA, group G which received both SIMP and CsA, and group H
      which received vehicles. SIMP solution (1 mm) was instilled every two hours and
      2% cyclosporin was instilled four times a day, this was carried out for as long
      as 6 weeks after surgery. At one, two, four, and six weeks after surgery, slit
      lamp examination was performed with haze gradings recorded, and corneal specimens
      were obtained from groups A, B, C, and D. In groups E-H, all rabbits were killed
      after six weeks of eyedrops instillation. Light microscopy and
      immunohistochemistry for collagen types III, IV, and VI were performed on the
      specimens obtained. Slit lamp examination and light microscopy revealed that SIMP
      significantly reduced corneal haze after PRK, but CsA did not.
      Immunohistochemistry revealed that deposition of types III and IV collagen was
      detected in ablated area in groups A-D, and SIMP reduced the frequency of
      positive staining for type III collagen. In groups E-F, corneas were normal.
      These findings suggest that SIMP significantly reduced corneal haze and the
      synthesis of type III collagen after excimer laser PRK in rabbits.

PMID- 9593633
TI  - Structural impairments in optic nerve of diabetic rats ameliorated with the
      aldose reductase inhibitor.
AB  - Structural impairments of optic nerve fibers in the streptozotocin-induced
      diabetic rat were investigated using morphometric analysis. The effect of aldose
      reductase inhibitor (ARI) on abnormalities in myelinated nerve fibers was also
      evaluated. Three months after the induction of diabetes, loss of body weight and
      significantly elevated levels of serum glucose were observed. Light microscopic
      examination revealed that the mean size of the optic nerve in the diabetic rat
      remained unchanged. Electron microscopic morphometry showed the significantly
      smaller cross-sectional size of axons and myelin but no change of myelinated
      fiber number. Reductions of myelinated fiber size was especially remarkable in
      the larger fibers. ARI treatment improved structural abnormalities without any
      changes in body weight and blood glucose level. Reduction of axon size and
      myelin/axon ratio was completely inhibited by ARI treatment. These findings
      suggest that structural impairment may contribute to the abnormalities of
      psychophysical and electrophysiological measurements detected in diabetes.
      Moreover, ARI treatment, which can improve the polyol metabolism, may have a
      beneficial effect on optic nerve impairment in diabetes.

PMID- 9593634
TI  - Expression of tyrosinase and the tyrosinase related proteins in the Mitfvit
      (vitiligo) mouse eye: implications for the function of the microphthalmia
      transcription factor.
AB  - Mitf (Microphthalmia transcription factor), a basic-helix-loop-helix zipper
      protein, encoded at the microphthalmia (Mitf) locus, regulates the transcription
      of the gene encoding tyrosinase, the rate-limiting enzyme in melanin
      biosynthesis, by binding the DNA sequence CATGTG. This binding site is present
      also in the genes encoding two tyrosinase related proteins, TRP-1 and TRP-2. To
      gain insight into the function of Mitf in vivo, we determined whether there was a
      difference in the levels of these proteins in the RPE/choroid of the vitiligo
      (Mitfvit) mouse, in which there is a mutation of the Mitf gene. This mouse has
      alteration of RPE pigmentation and function that presumably leads to slow
      progressive loss of photoreceptor cells. The RPE/choroid was dissected from eyes
      of vitiligo and C57BL/6 wild-type mice at postnatal ages 2, 4, 7, 10, 14, 21 and
      42 days. Extracts of pooled tissues were subjected to electrophoresis and
      immunoblotting. The levels of tyrosinase, TRP-1 and TRP-2 were determined
      densitometrically following immunodetection with rabbit antipeptide antisera. In
      addition, the tyrosine hydroxylase activity of tyrosinase as assayed
      radiometrically. Levels of TRP-1 were 3-7 fold greater in control RPE/choroid
      compared with mutants. This marked difference in protein level was observed at
      the earliest age examined (P2) and persisted throughout the first two weeks.
      Tyrosinase levels in mutants were similar to controls at P2 and P4, but were
      reduced at P10 and beyond. Tyrosinase activity was diminished also in mutants by
      P10. Levels of TRP-2 were similar between mutants and controls, although the
      typical decrease seen in controls after P14 was attenuated in the mutant mice.
      There is a significant reduction in the level of TRP-1 in the RPE/choroid of the
      Mitfvit mouse. The data suggests that transcription of the gene encoding TRP-1 is
      extremely dependent upon functional Mitf. It provides in vivo evidence that Mitf
      regulates the transcription of the gene encoding TRP-1 as well as tyrosinase.

PMID- 9593635
TI  - The advanced glycation endproduct pentosidine induces the expression of PDGF-B in
      human retinal pigment epithelial cells.
AB  - Advanced glycation endproducts have been implicated in a number of diabetic and
      aging changes. Some of these effects occur in part through induction of cytokines
      such as platelet-derived growth factor (PDGF), which is expressed by the retinal
      pigment epithelium (RPE). In this study, cultures of RPE were evaluated for PDGF
      expression after treatment with pentosidine, a well characterized advanced
      glycation endproduct. Northern analysis provided evidence for the increased
      expression of a 3.7 kb PDGF-B transcript over unstimulated controls in the
      established ARPE-19 cell line. Western analysis demonstrated increased PDGF-BB
      protein in conditioned medium compared to controls of ARPE-19 cells. In addition,
      two different early passage cultures of RPE showed increased PDGF-BB protein
      after pentosidine treatment compared to unstimulated controls. The enhanced
      production of PDGF-BB could play a role in the maintenance of the RPE-Bruch's
      membrane complex and influence changes associated with diabetes and aging.

PMID- 9593636
TI  - Peptidergic innervation of the rat cornea.
AB  - Corneal nerves regulate corneal epithelial integrity, proliferation, and wound
      healing. The mechanisms by which the nerves mediate their effects remain poorly
      understood; however, the release of biologically active neuropeptides has been
      hypothesized. The purpose of the current investigation was to determine the
      relative densities, distribution patterns, and origins of rat corneal nerves
      containing each of eight different neuropeptides, calcitonin gene-related peptide
      (CGRP), substance P (SP), galanin (GAL), neuropeptide Y (NPY), methionine
      enkephalin (M-ENK), vasoactive intestinal polypeptide (VIP), somatostatin (SOM),
      and cholecystokinin (CCK). In the first set of experiments, immunohistochemical
      demonstrations of the above neuropeptides were performed on free-floating corneal
      sections cut tangential to the corneal surface. The results showed that six of
      the peptides, CGRP, SP, GAL, NPY, M-ENK, and VIP were present in rat corneal
      nerves. The innervation patterns of corneal nerves containing each of these six
      peptides were then documented by mapping all fibers in serial sections from
      select corneal quadrants onto a series of line drawings by using a drawing tube.
      In the second set of experiments, the origins of the corneal peptidergic nerve
      fibers were determined by selective ocular denervations. Unilateral combined
      sensory and sympathetic ocular denervations or unilateral sympathetic ocular
      denervations were performed in adult rats by transecting the ophthalmomaxillary
      nerve and/or removing the superior cervical ganglion. After 5-7 days, each of the
      ipsilateral corneas was sectioned and processed immunohistochemically for the
      presence of one of the six peptides found in experiment one, and the fibers that
      survived the ocular denervations were plotted onto line drawings. Ocular
      denervations revealed that corneal peptidergic nerves have sensory (CGRP, SP, and
      GAL), sympathetic (NPY), and parasympathetic (GAL, NPY, M-ENK, and VIP) origins.
      The results of this investigation have shown that the peptidergic innervation of
      the rat cornea is more extensive and complex than previously reported. This is
      the first investigation to show the presence of GAL in the rat cornea, and the
      first to demonstrate the presence of NPY-, VIP-, and M-ENK-IR nerve fibers in the
      cornea of any species.

PMID- 9593637
TI  - Parasympathetic innervation of the rat cornea.
AB  - The mammalian cornea receives a dense sensory innervation and a modest
      sympathetic innervation. The purpose of the current study was to determine if the
      rat cornea is also innervated by parasympathetic nerves. In the first set of
      experiments, unilateral combined sympathetic and sensory ocular denervations were
      performed in adult rats by surgical removal of the superior cervical ganglion and
      intracranial transection of the trigeminal ophthalmomaxillary nerve. Completeness
      of the denervation procedure was verified postmortem by a variety of macroscopic
      and immunohistochemical methods. Five to twelve days later, the corneas were
      serially sectioned tangential to the ocular surface and processed
      immunohistochemically with antibodies against the pan-neuronal markers, protein
      gene product 9.5 (PGP-9.5) and peripherin. In every animal a small, but constant,
      population of corneal and limbal immunoreactive fibers were unaffected by the
      surgical denervations and were concluded to derive from parasympathetic ganglia.
      In the second set of experiments, the origins of the rat corneal innervation were
      determined by applying the neuroanatomical tracer, wheat germ agglutinin
      horseradish peroxidase (WGA-HRP) to the central cornea. Two to four days later,
      the trigeminal, superior cervical, ciliary, accessory ciliary and pterygopalatine
      ganglia were sectioned and analysed for the presence of HRP-labeled neurons.
      Examination of the corneal application site and associated ocular tissues
      revealed no evidence of tracer spread into neighbouring structures. Small numbers
      (0-6 per animal) of HRP-labeled neurons were observed in the ipsilateral ciliary
      and accessory ciliary ganglia of most animals. The results of these carefully
      controlled studies provide strong anatomical evidence of a modest parasympathetic
      innervation of the rat cornea.

PMID- 9593638
TI  - pH regulation in horizontal cells of the skate retina.
AB  - To examine the mechanisms by which horizontal cells regulate intracellular pH
      (pHi), measurements were recorded from isolated cells enzymatically dissociated
      from the skate retina utilizing the pH-sensitive dye BCECF. In a HCO3--containing
      Ringer solution, steady-state pHi was 7.32+/-0.13 (mean+/-S.D., n=70). Recovery
      from acidification was examined using the NH4+ prepulse technique. When NH4+ was
      removed from the extracellular solution, pHi dropped rapidly to approximately 0.3
      pH units below the initial baseline, and then recovered at an initial rate of
      approximately 0.072 pH units/min. During recovery of pHi after the acid load, the
      removal of Na+ or the addition of amiloride from a HCO3--free extracellular
      solution reduced the rate of recovery by 79%+/-11% and 69%+/-14%, respectively.
      In the presence of DIDS, which inhibits primarily anion transport, or during the
      removal of Na+, the recovery from acidification was reduced by 83%+/-10% and
      70%+/-11%, respectively, as compared to the control value in HCO3--containing
      solution. These results suggest that the skate horizontal cell possesses a Na/H
      exchanger as well as a Na+-and HCO3--dependent mechanism for removal of excess
      acid. Removal of HCO3- or Cl- from the extracellular solution had little effect
      on pHi, but removing external Na+ induced a marked decrease in pHi that fell at
      an initial rate of approximately 0.3 pH units min-1. This rate of acidification
      was decreased by 58%+/-19% in the presence of DIDS (500 micron) and reduced by
      28%+/-13% with the addition of amiloride (2 mm). Thus, Na- and HCO3-dependent
      transport was about 2-fold more active than Na/H exchange during low Na+-induced
      acidification. The intrinsic pH-buffer capacity, determined from the pHi change
      induced by incremental reductions in the [NH4+] of the extracellular solution,
      was 24.2 mm/pH unit at the horizontal cell's resting pHi. Moreover, pHi was
      relatively insensitive to changes in membrane potential; in experiments under
      whole-cell voltage clamp (-70 mV), intracellular pH remained constant during
      depolarizing voltage swings to -30 mV or +30 mV, as well as during
      hyperpolarizing pulses to -90 or -110 mV.

PMID- 9593639
TI  - Cloning, high level-expression and characterization of human lens
      thioltransferase.
AB  - Polymerase chain reaction (PCR) primers, directed against the nucleotide sequence
      of pig liver thioltransferase (PLTT) were used to amplify human lens
      thioltransferase (HLTT) from a pool of human lens cDNA. The 520 bp PCR fragment
      obtained was cloned unidirectionally into pCR 3.1-Uni vector and sequenced. The
      cDNA sequence of the lens thioltransferase had 98% and 87% homology to pig liver
      and human placental thioltransferases (TTase) respectively. Nhe1 and EcoR1
      fragment of the recombinant PCR 3.1-Uni vector was subcloned in pET 23a
      Expression vector. High level expression of HLTT was accomplished in Escherichia
      coli and the expressed protein was characterized by immunoblot analysis with anti
      PLTT and N-terminal amino acid sequence analysis. The recombinant enzyme
      efficiently dethiolated protein thiol mixed disulfides conjugated to both cystine
      (PSSC) and glutathione (PSSG) and had a significant dehydroascorbate reductase
      activity. Human lens thioltransferase thus displayed structural and functional
      characteristics identical to pig liver and human placental thioltransferases.

PMID- 9593640
TI  - Thioltransferase is present in the lens epithelial cells as a highly oxidative
      stress-resistant enzyme.
AB  - The redox homeostasis is controlled by several enzyme systems. Sulfhydryl groups
      in lens proteins are very sensitive to oxidative stress and can easily conjugate
      with nonprotein thiols (S-thiolation) to form protein-thiol mixed disulfides. We
      have observed an elevation of protein S-S-glutathione (PSSG) and protein-S-S
      cysteine (PSSC) in cataractous lenses from humans and from animal models
      subjected to oxidative stress. We also observed that these protein-thiol mixed
      disulfides could be spontaneously dissociated and lowered to basal levels if the
      lens which was pre-exposed to H2O2 was subsequently cultured in H2O2-free medium.
      This suggests that the lens has a system to repair oxidative damage through
      dethiolation thereby restoring its redox homeostasis. In other tissues, an
      enzyme, thioltransferase (TTase), has been shown to be responsible for
      thiol/disulfide regulation. We recently demonstrated the presence of this enzyme
      in the lens and in cultured lens epithelial cells. Here, we investigated the
      response of TTase to H2O2 stress and its possible repair function in cultured
      lens epithelial cells. Rabbit lens epithelial cell line N/N 1003A was raised to
      confluence, trypsinized and plated at 0.8 million cells per 60 mm culture dish.
      The cells were incubated overnight in Eagle's minimum essential medium (MEM) with
      1% rabbit serum and then in serum-free MEM for 30 min before a bolus of 0.5 mm
      H2O2 was added. At intervals of 5, 15, 30 min and up to 3 hr, the cells were
      harvested and used for enzyme assays for TTase, glutathione reductase (GR),
      glutathione peroxidase (GPx) and glyceraldehyde-3-phosphate dehydrogenase (G
      3PD). Free GSH, total SH and PSSG and PSSC were also determined. Hydrogen
      peroxide in the medium was measured at each time point. Cells incubated without
      H2O2 were used as controls. The results showed that the H2O2 concentration was
      reduced to 50% within 30 min and was undetectable at 2 hr. Cellular GSH dropped
      to 40% within 5 min and stayed at this level before it began to increase at 90
      min and completely recovered by 2 hr. The total SH groups were similar to free
      GSH. PSSG and PSSC increased 6.5 and 2 times respectively before 30 min and then
      decreased when GSH started to recover. G-3PD was most sensitive to H2O2 and lost
      95% activity within 5 min. The activity was regained quickly when H2O2 diminished
      in the medium. A similar but less severe pattern was observed in both GPx (60%
      loss at 60 min) and GR (30% loss at 90 min). In contrast, TTase activity remained
      constant during the entire 3 hr. Only when a higher dose of H2O2 (0.8-1.0 mM) was
      used, did TTase activity show a brief loss (<30% at 60 min) and a swift recovery.
      Cells exposed to H2O2 exhibited a normal morphology with no evidence of DNA
      fragmentation. The lens epithelial cells showed a remarkable ability to repair
      the early damages induced by H2O2. The unusual oxidative stress-resistant
      property displayed by TTase, coupled with its known function suggest that it
      plays an important role in the repair of oxidative damage.

PMID- 9593641
TI  - Pharmacokinetics of topical beta-adrenergic antagonists in rabbit aqueous humor
      evaluated with the microdialysis method.
AB  - The microdialysis method was used to evaluate the pharmacokinetics of the beta
      adrenergic antagonists carteolol and timolol and the new ophthalmic solution WP
      934 in rabbit aqueous humor, following instillation. A probe with a microdialysis
      membrane (length, 5 mm; diameter, 0.2 mm) was implanted in the anterior chamber
      of the pigmented rabbit and perfused with Ringer's solution. Twenty microliters
      of 0.5% timolol maleate (0.5% Timoptol(R)), 2% carteolol hydrochloride (2%
      Mikelan(R)), or a novel preparation of 0.5% timolol maleate (WP-934) that gels
      after instillation were then instilled. The concentrations of these drugs in
      dialysates were measured using high-performance liquid chromatography and an
      electrochemical detection system. In vitro relative recovery of the membrane with
      timolol and carteolol was approximately 17.5% and 21. 6%, respectively. Timolol
      and carteolol levels in aqueous humor increased rapidly after instillation of
      Timoptol and Mikelan and reached maximal levels (Cmax) within 60 minutes. The
      Cmax of carteolol (4.25 microg ml-1) was lower than that of timolol (5.52 microg
      ml-1), suggesting that the corneal permeability of timolol is higher than that of
      carteolol. After instillation of WP-934, the Cmax of timolol (12.32 microg ml-1)
      was 2.2-fold higher than that after instillation of Timoptol. However, t1/2
      values of beta-adrenergic antagonists after instillation of the three
      preparations were not significantly different. These data suggest that the
      microdialysis technique is useful for continuous monitoring of aqueous levels of
      beta-blockers and for analysis of their pharmacokinetic parameters while
      requiring much fewer animals than conventional sampling with paracentesis.

PMID- 9593642
TI  - Structural arrangement of lens fiber cell plasma membrane protein MP20.
AB  - The membrane topology of the bovine lens fiber cell plasma membrane protein MP20
      has been examined using anti-peptide antibodies and the hydrophobic label 3
      (trifluoromethyl)-3-(m-[125I]iodophenyl)diazerine ([125I]TID). The specificity of
      the affinity-purified anti-peptide polyclonal antibodies, directed against four
      separate hydrophilic segments of MP20, was established by immunodot blots,
      Western immunoblotting and ELISA. Western immunodetection of protease-treated,
      urea-washed lens membranes indicated that each of the segments of MP20 identified
      by the anti-peptide antibodies was accessible to proteases indicating their
      likely extramembranous location. Immunoelectron microscopy of junctional lens
      membrane immunolabeled with MP20 anti-peptide antibodies directed against two
      segments predicted to be on the extra-cellular face of the lens fiber cell plasma
      membrane suggests these segments may actually be located on the cytoplasmic
      plasma membrane face. Transmembrane segments of MP20, identified using the
      hydrophotic photo-affinity label [125I]TID, were isolated and sequenced. Only
      three of the four previously proposed transmembrane segments of this protein were
      significantly labeled with this reagent. Based on these results and previously
      reported information regarding MP20, a new topological model is proposed for the
      arrangement of MP20 in the lens fiber cell plasma membrane. The new topological
      model of MP20 includes two alpha-helical and two beta-strand transmembrane
      segments.

PMID- 9593643
TI  - Announcements 

PMID- 9593644
TI  - Autoregulation of estrogen and androgen receptor mRNAs and downregulation of
      androgen receptor mRNA by estrogen in primary cultures of lizard testis cells.
AB  - Steroid hormones regulate many developmental and physiological processes via
      specific receptors whose number can be up- or downregulated. The regulation of
      estrogen (ER) and androgen (AR) receptor mRNAs in primary cultures of lizard
      testis is described. The high degree of homology between the probes used and the
      receptor mRNAs in lizard testis was consistent with the high-stringency
      hybridisation conditions and the molecular size of ER mRNAs (7.4 and 4.5 kb) and
      AR mRNA (9.5 kb). Primary cultures of testis cells revealed a time- and drug
      dependent relationship between ER and AR mRNAs. 17beta-oestradiol (E)
      autoregulated ER mRNA and downregulated AR mRNA. The antiestrogen ICI 164,384
      reversed the latter effect. Cycloheximide (Cy), to inhibit protein synthesis, in
      combination with E, impaired the AR mRNA expression. Testosterone (T)
      autoregulated the expression of its own receptor mRNA whereas this effect was
      reversed by both flutamide (F) and Cy. Dose-response experiments showed that low
      concentrations of steroids (E or T 10(-12) M) increased ER or AR mRNA levels,
      respectively. These results suggest that both estrogen and androgen may
      autoregulate the expression of their own receptor mRNAs. Since in lizard testis
      androgens are significantly involved in meiosis and spermiogenesis and E
      dramatically impairs the AR mRNA expression, the latter effect may be key in
      regulating certain phases of reproduction.

PMID- 9593645
TI  - Stress-reactive response of the gerbil pineal gland: concretion genesis.
AB  - The reaction of pinealocytes and glia cells to an acute immobilization stress and
      their poststress recovery was studied in gerbils. Pinealocytes responded to
      immobilization with an increased peptidergic activity and formation of new
      concretions, whereas glia cells with an increased growth of interstitial
      concretions. The occurrence of degenerating pinealocytes indicated deleterious
      actions of immobilization stress on functionally stimulated cells. The
      pyroantimonate method to detect Ca2+ demonstrated enlarged crystalline profiles
      (Ca2+ crystallization into hydroxyapatite) in functionally stimulated
      pinealocytes and the accumulation of Ca2+ in the interstitial concretion. The
      pinealocyte concretions did not show the Ca2+ accumulation. The pineal gland
      poststress recovery was manifested by a reduced functionally stimulated
      pinealocyte activity and a protracted increase in glia cell activity. It is
      suggested that the physiological relevance of the crystallization of Ca2+ into
      hydroxyapatite is to maintain a noradrenalin-stimulated Ca2+ influx at an optimal
      level during attentuated pinealocyte turnover. The interstitial concretions may
      lower the extracellular Ca2+ concentrations and thereby stimulate pinealocytes
      and restrict an increased Ca2+ influx.

PMID- 9593646
TI  - Gilthead seabream (Sparus aurata) vitellogenin: purification, partial
      characterization, and validation of an enzyme-linked immunosorbent assay (ELISA).
AB  - VTG was purified from seabream Sparus aurata plasma by ion exchange
      chromatography on a DEAE-Sepharose column. The vitellogenin was characterized and
      its properties were determined. The molecular mass of the native form, obtained
      by Sephadex G-200 column, was around 450 kDa, whereas an apparent molecular mass
      of 180 kDa was detected by electrophoresis under denaturing and reducing
      conditions, suggesting a dimeric form for the native protein. The presence of
      carbohydrates was determined using concanavalin A, while the presence of
      phosphate groups was detected by Stains-all, a cationic stain. These data
      together with the sex specificity, the estrogen inducibility, and the cross
      reactivity of the abVTG against the major yolk proteins identifies this protein
      as vitellogenin. The validated ELISA was used for a rapid and reliable
      measurement of plasma VTG changes related with those of estradiol-17beta in
      female broodstock.

PMID- 9593647
TI  - Insulin-like growth factor (IGF)-I but not IGF-II promotes lean growth and feed
      efficiency in broiler chickens.
AB  - The efficacy of exogenous IGFs to stimulate growth and modulate protein and fat
      deposition was examined in a number of broiler chicken lines. From around 600 g
      body weight the chickens received a continuous infusion of vehicle (0.1 M acetic
      acid), human recombinant IGF-I or [Gly1]IGF-II at 300 microg/kg body weight per
      day, or a combined infusion of 150 microg/kg/day of each IGF for 2 weeks.
      Experiment 1 used commercial broiler female chickens and included measurements of
      nitrogen balance, Ntau-methylhistidine excretion and muscle protein synthesis
      rates. In Experiment 2 the same treatments were applied to three experimental
      lines of chickens selected for high food consumption (relatively fat), high food
      utilisation efficiency (relatively lean), or at random (control). IGF-I, but not
      IGF-II, significantly increased growth rate and food utilisation efficiency by
      around 10-15% in each experiment, an effect which was consistent across all
      genotypes. Nitrogen balance was significantly increased by IGF-I in Experiment 1
      as was carcass nitrogen content in Experiment 2, indicating that the increased
      growth was in lean tissue. Carcass fat was consistently reduced in chickens
      receiving IGF-I and was related to the levels of circulating IGF-I (r2 = 0.30, P
      < 0.01) but not triiodothyronine. Protein synthesis rates were unaffected by
      treatment and could not account for increased growth rate. However, there was a
      significant reduction in Ntau-methylhistidine excretion indicating a reduced rate
      of muscle protein breakdown in IGF-I-treated chickens (1. 56%/day vs 2.05%/day
      for IGF-I-treated vs controls, P < 0.05). The efficiency of feed utilisation was
      inversely related to the rate of protein breakdown (r2 = 0.25, P < 0.01). In
      conclusion, these experiments are the first to report an enhancement of growth
      and food utilisation efficiency by broiler chickens receiving exogenous IGF-I.
      Our results show that IGF-I may be important in controlling the growth and
      efficiency of food utilisation of young chickens at least in part by modulating
      the rates of protein breakdown.

PMID- 9593648
TI  - Endocrine profiles of female striped bass (Morone saxatilis) in captivity, during
      postvitellogenesis and induction of final oocyte maturation via controlled
      release GnRHa-delivery systems.
AB  - Plasma levels of reproductive and thyroid hormones were measured in captive
      striped bass females during postvitellogenesis and the spawning period (March
      June). Circulating gonadotropin II (GtH II), 17,20beta-dihydroxy-4-pregnen-3-one
      (17,20beta-P), and 17,20beta, 21-trihydroxy-4-pregnen-3-one (17,20beta,21-P)
      remained low and unchanged in nonmaturing females, while 17beta-estradiol (E2)
      and testosterone (T) declined throughout postvitellogenesis. Plasma thyroxine
      (T4) declined significantly in mid-April, while triiodothyronine (T3) increased
      in mid-May. The only female that ovulated spontaneously had markedly different
      E2, T, and T3 profiles during postvitellogenesis, and had a surge in plasma GtH
      II during final oocyte maturation (FOM). The lack of a GtH II surge is presumably
      responsible for the absence of FOM, but earlier, and as of yet unknown, endocrine
      disruptions during postvitellogenesis may determine the female's ability to
      undergo FOM. Treatment of females with a gonadotropin-releasing hormone agonist
      (GnRHa)-delivery system induced FOM and ovulation within 3 and 10 days,
      respectively, and resulted in the production of fertile eggs. Plasma GtH II
      increased continually after GnRHa implantation, even in the presence of declining
      GnRHa plasma levels. Plasma E2 increased first and peaked prior to FOM, whereas T
      peaked at the peripheral germinal vesicle (GV) stage. Plasma 17,20beta-P and
      17,20beta,21-P increased dramatically at the GV breakdown (GVBD) stage. Plasma T4
      was unaffected by the GnRHa treatment, whereas T3 decreased after GnRHa
      implantation and remained low throughout FOM. Based on the observed hormonal
      profiles, FOM can be separated into an early phase (lipid-droplet coalescence, GV
      migration) associated with E2 and T elevations, and a late phase (yolk-globule
      coalescence, GVBD) associated with 17,20beta-P and 17,20beta,21-P elevation.

PMID- 9593650
TI  - Morphology of the thyroid in coastal and noncoastal populations of the koala
      (Phascolarctos cinereus) in Queensland.
AB  - The gross morphology, histology, and ultrastructure of the thyroid gland of the
      koala, Phascolarctos cinereus, is described. Generally, the glands were found to
      contain large-diameter follicles in association with an epithelium of low height.
      Morphometric analysis demonstrated a high relative thyroid weight (0.3 +/- 0.2
      g/kg) for koalas compared with the 0.07-0.24 g/kg typical of eutherian mammals
      and 0.03-0.1 g/kg found in other marsupials. The relative thyroid weight of
      glands (0.33 +/- 0.21 g/kg) from the coastal population (less than 28 km from the
      coastline) was found to be significantly higher (ANOVA: P = 0.007, significant at
      the 1% level) than that for glands (0.21 +/- 0.11 g/kg) of noncoastal koalas
      (greater than 28 km from the coastline). Follicle size was positively correlated
      (at the 0.1% level) with relative thyroid weight in the overall koala sample. The
      presence of C cells, occurring singly in the epithelial layer, was demonstrated
      in electron micrographs. Structural features such as low epithelial height, large
      follicle length and width, and large intercellular spaces in association with low
      concentrations of free T4 (3.3 +/- 2.1 pM) and free T3 (1.4 +/- 0.9 pM) as
      reported previously (Lawson et al., 1996) are consistent with an unusually low
      level of glandular activity in the koala thyroid even though iodine
      concentrations in the thyroid gland [4.7 +/- 1.6 mg/g (dry weight)] as well as
      leaf [0.8 +/- 0.3 microg/g (dry weight)] and soil samples [3.8 microg/g (dry
      weight)] from the koalas' habitat appear unremarkable.

PMID- 9593649
TI  - Plasma calcium and stanniocalcin levels of male tilapia, Oreochromis mossambicus,
      fed calcium-deficient food and treated with 1,25 dihydroxyvitamin D3.
AB  - The vitamin D metabolite 1,25 dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) was
      injected ip (5 microg/kg-1 body mass daily) into male tilapia, Oreochromis
      mossambicus, fed calcium-deficient food. Plasma calcium (total and free) and
      stanniocalcin levels, as well as calcium contents of vertebral and opercular bone
      and scales, were determined on days 1, 3, and 5. In the treated fish, total
      plasma calcium levels increased on days 3 and 5. Plasma-free calcium levels
      remained unaffected. Plasma stanniocalcin levels increased, indicating a response
      of the Stannius corpuscles to redress 1, 25(OH)2D3-induced hypercalcemia. The
      calcium contents of bone, operculum, and scales were unchanged. It is concluded
      that in fish, which lack parathyroid hormone, 1,25(OH)2D3 is hypercalcemic and
      its action is independent of dietary calcium.

PMID- 9593652
TI  - Immunocytochemical identification of endocrine cells in the pancreas of the fruit
      bat, Rousettus aegyptiacus.
AB  - The fruit bat, Rousettus aegyptiacus, is able to absorb large amounts of glucose
      in very short periods of time. This ability is partly reflected by the structure
      of the gastrointestinal tract and pancreas. The aim of this study was to confirm
      preliminary histochemical studies of the bat pancreas and to identify and
      quantitate endocrine cells by immunocytochemical techniques in order to
      understand the ability of the bat to absorb these large amounts of glucose.
      Endocrine cells were distributed in islets throughout the gland and also occurred
      as discrete cells in the exocrine ducts. Three-dimensional reconstruction and
      quantitation showed that the endocrine component of the pancreas occupied 9.1% of
      the total volume. This is far more than that reported in any other species. Four
      endocrine cell types were demonstrated. Insulin (beta) cells (51.4%) were located
      throughout the islet and extended between the glucagon (alpha) cells (30.6%).
      Somatotostatin (delta) cells (8.8%) and pancreatic polypeptide (PP) cells (17.1%)
      were irregularly scattered throughout the islets. While the percentage of alpha,
      beta, and delta cells was similar to that in other species, the percentage of PP
      cells was higher. The high percentage of endocrine tissue found in the pancreas
      of the fruit bat may reflect metabolic adaptations involved in the absorption of
      the high carbohydrate diet of this animal.

PMID- 9593651
TI  - Hyperglycaemic hormones inhibit protein and mRNA synthesis in in vitro-incubated
      ovarian fragments of the marine shrimp Penaeus semisulcatus.
AB  - The present work shows for the first time that peptides belonging to the
      Crustacean hyperglycaemic hormone family (CHH-family hormones) from Penaeus
      japonicus affect protein and mRNA synthesis in in vitro-incubated ovarian explant
      fragments removed from vitellogenic females of Penaeus semisulcatus. Reduced
      levels of protein synthesis, determined by TCA-precipitable 35S-labeled proteins,
      were found in the presence of crude sinus gland extracts from both P.
      semisulcatus and P. japonicus. A similar inhibitory effect compared to controls
      was found with each of the seven CHH-family peptides. Non-CHH-family peptides did
      not reduce protein synthesis. Crude sinus gland extracts prepared from P.
      semisulcatus were at least 20-fold more effective than sinus gland extracts of P.
      japonicus. The inhibition level was directly related to the concentration of the
      peptide in the incubation media, but its degree varied among the different tested
      peptides. The profile of proteins synthesized during in vitro incubation was
      analyzed using polyacrylamide gel electrophoresis under denatured and reduced
      conditions (SDS-PAGE), followed by autoradiography. Synthesis of several proteins
      was reduced, including proteins with electrophoretic mobility similar to that of
      vitellin. Immunoprecipitation with antiserum prepared against native ovarian
      vitellin confirmed the inhibitory effect of CHH-family peptides on vitellin
      synthesis. The crude sinus gland extract and CHH-family peptides also inhibited
      RNA synthesis, as determined by [3H]uridine incorporation into mRNA of ovarian
      fragments. It is concluded that in addition to their role in carbohydrate
      metabolism, CHH-family peptides may also influence ovarian physiology in
      crustaceans.

PMID- 9593653
TI  - Hormonal correlates of environmentally induced metamorphosis in the Western
      spadefoot toad, Scaphiopus hammondii.
AB  - Tadpoles of several amphibian species have been shown to accelerate metamorphosis
      when their ponds dry. To understand the proximate mechanisms that mediate the
      developmental response to pond drying, I analyzed changes in endocrine activity
      in tadpoles of the Western spadefoot toad (Scaphiopus hammondii) exposed to
      experimental water volume reduction in the laboratory. Tadpoles exposed to a
      declining water level accelerated metamorphosis compared with tadpoles raised in
      a constant high water environment. The acceleration of development was associated
      with the precocious elevation of whole-body contents of the hormones that control
      metamorphosis, the thyroid hormones thyroxine (T4) and triidothyronine (T3), and
      the interrenal steroid corticosterone (CORT). The precocious activation of the
      thyroid system preceded external morphological change (i.e., increase in hind
      limb length, developmental stage) by 3 days. To test if tadpoles are capable of
      responding rapidly to water volume reduction, mid-prometamorphic tadpoles (Gosner
      Stage 37-38) were raised in a constant high water environment (10 L) and then
      transferred to either 1 or 10 L. Tadpoles transferred to 1 L exhibited
      significant metamorphic changes by 48 h after transfer. In addition, dramatic
      elevations in whole-body T4, T3, and CORT contents were evident at this time
      point. Thus, the metamorphic response to pond drying is likely driven by the
      activation of the thyroid and interrenal axes, the hormones of which control
      metamorphosis. Furthermore, this response is rapid, occurring within 48 h after
      exposure to the desiccating environment.

PMID- 9593654
TI  - Effect of exogenous progesterone on luteinizing hormone secretion in domestic
      turkey hens at different reproductive states.
AB  - To determine effects of progesterone (P4) treatment on luteinizing hormone (LH)
      secretion in turkey hens, two trials were conducted. Trial 1 was to determine
      changes in LH, P4, and testosterone (T) during photostimulation. Photosensitive
      turkey hens were maintained under short days (SD) of 6 h light and 18 h dark. At
      the beginning of Trial 1, blood samples were taken daily for 4 days, then one
      half of the hens were switched to long days (LD) of 14 h light and 10 h dark, and
      daily blood samples were continued until 5 days after eggs were laid by all the
      hens switched to LD. Concentrations of LH, P4, and T increased significantly 1
      day after switching hens from SD to LD, but the increase in P4 was initially low
      with a further increase occurring by 3 days prior to first eggs. In Trial 2,
      turkey hens were injected with exogenous P4 to determine if P4 is an initiator of
      the preovulatory surge of LH. P4 or vehicle were injected im in hens at three
      different reproductive states: (1) while hens were maintained under SD, (2) on
      the 5th day after hens were switched from SD to LD, and (3) after hens were
      laying for 1 week. The hens were serially bled at 10-min intervals for 8 h to
      monitor changes in LH and P4. After 2 h of serial bleeding, P4 or vehicle was
      injected and bleeding was continued for an additional 6 h. After P4 injection,
      its concentration increased rapidly from a base level of 0.25-1.20 ng/ml to a
      postinjection high level of 4.42-6.10 ng/ml within 20 min. The high level of P4
      was then maintained throughout the remaining 6 h. No increases of LH secretion
      were observed after P4 or vehicle injection in hens at either State 1 or State 2.
      Small increases of LH secretion were detected about 2 h after P4 injection in
      hens at State 3, but these increases were not significantly above vehicle
      injected controls. Thus, there was no positive feedback effect of P4 injection on
      LH secretion in this trial. These results suggest that P4 might not induce LH
      secretion in immature or mature turkey hens and might not be the factor which
      induces the preovulatory surge of LH in laying turkey hens. Nonsteroidal factors
      of ovarian origin might be involved in regulating the preovulatory surge of LH in
      turkey hens.

PMID- 9593655
TI  - A multiscale model of plant topological structures 
AB  - In applications dealing with plant growth modeling, increasing attention is being
      devoted to the topological structure of plants. Different models, based on tree
      graphs, have been introduced to represent plants. These models assume that the
      scale of description is fixed. However, this hypothesis is too restrictive for
      new modeling applications that aim to tackle analysis or simulation of plant
      growth at different time and space scales. In order to make such multiscale
      descriptions available to computer applications, we have defined a general
      methodology for measuring and representing multiscale plant topological
      structures. This paper discusses the design of a model of plant topological
      structures and sketches out its general formal properties. The model supports
      multiscale, attributed and time-varying descriptions of plants. It is intended to
      be used for plant analysis methodologies and plant growth simulations.Copyright
      1998 Academic Press Limited

PMID- 9593656
TI  - Computer simulation of fat and muscle burn in long-distance bird migration 
AB  - The mechanical power required from a bird's flight muscles was recalculated at
      regular intervals (default 6 min), and the energy consumed in the interval was
      accounted for by reducing fuel reserves, which also reduced the all-up mass and
      the body cross-sectional area. Part of the energy requirement was met by
      consuming flight muscle tissue, according to one of three alternative "muscle
      burn criteria". These were (1) specific work held constant, (2) power density
      held constant and (3) muscle mass held constant, i.e. no muscle consumed. Holding
      the specific work constant produced results in the best agreement with the
      results of other studies. This criterion was therefore selected to compare
      simulated flights of three very different species whose flight and migrations
      have been extensively studied, (1) Thrush Nightingale (Luscinia luscinia), (2)
      Knot (Calidris canutus) and (3) Whooper Swan (Cygnus cygnus). The ratio of
      protein to fat consumed ranged from 0.19 to 0.36, depending mainly on the
      starting value assumed for the muscle fraction. Specific work and starting power
      density were much higher for the Whooper Swan than for the two smaller species,
      suggesting that the latter have power to spare for climbing to high cruising
      altitudes, whereas the swan has not. If all three species were able to reach high
      cruising altitudes, the result would be a large reduction in journey time, which
      in turn would result in a small increase in range, due to a saving of energy
      required for basal metabolism. On current assumptions, the proportion of the fuel
      energy spent on basal metabolism would be eight times higher in the Thrush
      Nightingale than in the Whooper Swan, consequently the gain in range due to
      flying high would be greater in the smaller bird. In order to run the simulation,
      assumptions have been made at the primary physical level, to calculate the
      mechanical power required, and also at the secondary physiological level, to
      convert this into fuel consumption. The physical assumptions mostly take the form
      of variables whose existence is not in doubt, but whose values are poorly known,
      whereas in the case of some of the most important physiological variables, even
      the principles are unknown. Attention is drawn to a number of problems in need of
      attention, including (1) the mass and energy requirements of respiratory and
      circulatory organs required to sustain aerobically a given level of mechanical
      power; (2) the capabilities of bird lungs at high altitudes; (3) the possibility
      that heart muscle and lung tissue may be consumed in flight; (4) the two
      "biological constants", isometric force per myosin fibril and inverse power
      density of mitochondria; (5) the energy density of different fuels, and the
      conversion efficiency of the flight muscles; and (6) the manner in which basal
      metabolism combines with other demands for power in an exercising animal.
      Copyright 1998 Academic Press Limited

PMID- 9593658
TI  - Mathematical modelling of 3-(3',4'-dichlorophenyl)-1,1-dimenthylurea action in
      plant leaves 
AB  - A mathematical model of the action of a photosystem II herbicide 3-(3',4'
      dichlorophenyl)-1, 1-dimenthylurea, DCMU, in plant leaves upon an external
      application is presented. The diffusion of DCMU in a plant tissue is described
      with the help of Fick's laws and the following reaction of the herbicide with the
      QB-binding site of photosystem II by the mass action theory. The model is used
      for a description of the effect of the herbicide on chlorophyll fluorescence
      induction (the O-J-I-P curve) measured with spring barley primary leaves
      submerged in the herbicide solution. The increase of the J step during the
      herbicide action is ascribed to an increase of the number of photosystem II
      centres with bound herbicide molecules and malfunctioning in the electron
      transport to the plastoquinone pool. The experimental data were fitted with the
      help of the mathematical model. Values of the diffusion coefficient and the
      second order rate constant of the reaction of the herbicide with photosystem II,
      obtained by the fitting procedure, are discussed.Copyright 1998 Academic Press
      Limited

PMID- 9593657
TI  - The use of the dimensionless Womersley number to characterize the unsteady nature
      of internal flow.
AB  - Dimensionless numbers are very useful in characterizing mechanical behavior
      because their magnitude can often be interpreted as the relative importance of
      competing forces that will influence mechanical behavior in different ways. One
      dimensionless number, the Womersley number (Wo), is sometimes used to describe
      the unsteady nature of fluid flow in response to an unsteady pressure gradient;
      i. e., whether the resulting fluid flow is quasi-steady or not. Fluids surround
      organisms which themselves contain fluid compartments; the behaviors exhibited by
      these biologically-important fluids (e.g. air, water, or blood) are
      physiologically significant because they will determine to a large extent the
      rates of mass and heat exchange and the force production between an organism and
      its environment or between different parts of an organism. In the biological
      literature, the use of the Womersley number is usually confined to a single
      geometry: the case of flow inside a circular cylinder. We summarize the evidence
      for a broader role of the Womersley number in characterizing unsteady flow than
      indicated by this geometrical restriction. For the specific category of internal
      flow, we show that the exact analytical solution for unsteady flow between two
      parallel walls predicts the same pattern of fluid behavior identified earlier for
      flow inside cylinders; i.e., a dichotomy in fluid behavior for values of Wo < 1
      and Wo > 1. When Wo < 1, the flow is predicted to faithfully track the
      oscillating pressure gradient, and the velocity profiles exhibit a parabolic
      shape such that the fluid oscillating with the greatest amplitude is farthest
      from the walls ("quasi-steady" behavior). When Wo > 1, the velocity profiles are
      no longer parabolic, and the flow is phase-shifted in time relative to the
      oscillating pressure gradient. The amplitude of the oscillating fluid may either
      increase or decrease as Wo > 1, as described in the text.

PMID- 9593659
TI  - Pattern and morphogenesis in skin.
AB  - Models dealing with the development of hair and feather follicles commonly
      predict that the factors initiating morphogenesis also specify patterns of
      follicle distribution. The factors have been postulated as chemical or mechanical
      instabilities which, at certain threshold concentrations, determine both the
      location of follicles and their form. The models tend to focus on the earliest
      waves of induction, where follicles develop at separate, non-randomly spaced
      initiation sites in skin. However, in many animals, there are later waves of
      initiation, some of which give rise to compound follicles. These are bundles of
      follicles that arise by branching from the necks of those formed earlier and
      share a common pilary canal when mature. In some species, compound follicles make
      the greatest numerical contribution to the follicle population. Measurements of
      the frequencies of single and branched follicles in sheep selection lines with
      different follicle densities (from previous studies by Moore et al.) revealed
      that the follicles which formed first during foetal life (primary and original
      secondary populations) were established at separately identifiable sites in the
      skin, called here "initiation sites". However, there were also later waves of
      development, contributing follicles exclusively by the process of branching (the
      derived secondary population). Final follicle densities were not correlated with
      the densities of initiation sites. The observations suggested that mechanisms
      specifying the positional values of initiation sites differed from those
      determining follicle number. The final densities of the follicle populations in
      the sheep lines were also highly negatively correlated with the diameters of the
      wool fibres grown. The close statistical relationship suggested that the two
      parameters were developmentally linked. However, whereas fibre characteristics
      are realised when the follicle is mature, density is established earlier, during
      foetal life. We have reconciled these observations with the following hypothesis:
      a population of cells, committed to a follicular pathway of development,
      differentiates in the skin at or before the first wave of initiation.
      Subpopulations of the committed cells subsequently participate in each follicle
      initiation event, the number in each subpopulation ultimately determining fibre
      dimensions. Follicle initiation continues until most or all of the original
      population have been utilised. Transplantation and skin recombinant studies have
      demonstrated that the cells forming the dermal papilla of the follicle
      participate in follicle initiation and have inductive effects on epidermal
      tissue. Papilla size is also correlated with fibre diameter in the mature
      follicle. These attributes are consistent with those described for the committed
      cell population.

PMID- 9593660
TI  - Time delays in density dependence are often not destabilizing 
AB  - Time delays in density dependence have been associated with regular and sustained
      fluctuations in population size. Mathematical models have found that delays that
      are long enough can produce limit cycles. In experimental populations with
      preadult and adult phases in the life cycle and density regulation in any of the
      phases, it has been found that the time delay represented by maturation time can
      produce fluctuations in adult size. This has been corroborated by mathematical
      models. The present study develops mathematical models of growth in this type of
      population. The analysis of these models indicate that when preadult cohorts do
      not overlap in space, and preadult mortality is affected by the density of
      preadults at the present moment, the time delay does not destabilize the
      population. However, with spatial overlap of preadult cohorts and the same
      mechanism of density dependence, time delays can be destabilizing. It is
      concluded that time delays in density effects during preadulthood are not
      necessarily destabilizing, and that fluctuations in population size can also be
      due to delays with density effects in preadulthood and adulthood, or exogenous
      agents. Copyright 1998 Academic Press Limited

PMID- 9593661
TI  - Mechanisms for positional signalling by morphogen transport: a theoretical study.
AB  - Gradients of cellular activities are ubiquitous in embryonic development. It is
      widely believed that the inhomogeneous spatial distribution of a morphogen would
      be able to set up such gradients. But how then does the morphogen propagate in
      the first place? Straightforward molecular diffusion is often proposed as a
      possible mechanism. We first show that, surprisingly, the mere binding of the
      diffusing morphogen to its membrane receptors suffices to prevent the
      establishment of a concentration-based positional signalling system. Instead, a
      flat, saturated distribution of receptor-bound morphogen builds up. Because the
      distribution spreads gradually from the morphogen source, however, cells may
      still know their position if they are able to integrate the morphogen signal in
      time. The irregularities of diffusion in the complex extracellular medium would
      in fact be partially compensated for by such time summation. Another, non
      exclusive possibility is that morphogen transport does not occur by simple
      diffusion only. We put forth a novel model of receptor-aided, directed diffusion
      that achieves a spatial distribution of morphogen. Our model is based, as an
      illustration, on the properties of members of the TGFbeta family of molecules. We
      show that two simple hypotheses regarding the kinetics of TGBbeta binding to its
      receptors suffice to establish a remarkable transfer mechanism whereby a
      morphogen such as activin could be both propagated along cell membranes, and
      transferred between cells that are in contact. The model predicts that morphogen
      propagation properties depend strongly on the closeness of cell-cell appositions,
      does not necessitate protein synthesis, accumulation or slow degradation (in
      contrast to the diffusion/time integration model), and that the morphogen is
      localised mostly on or close to cell membranes.

PMID- 9593662
TI  - Regulation of the calmodulin-stimulated protein phosphatase, calcineurin.

PMID- 9593663
TI  - Synapsin III, a novel synapsin with an unusual regulation by Ca2+.
AB  - Synapsins I and II are synaptic vesicle proteins essential for normal Ca2+
      regulation of neurotransmitter release. Synapsins are composed of combinations of
      common and variable sequences, with the central C-domain as the largest conserved
      domain. The C-domain is structurally homologous to ATPases, suggesting that
      synapsins function as ATP-dependent phosphotransfer enzymes. We have now
      identified an unanticipated third synapsin gene that is also expressed in brain.
      The product of this gene, synapsin IIIa, shares with synapsins Ia and IIa three
      conserved domains that are connected by variable sequences: the phosphorylated A
      domain at the amino terminus, the large ATP-binding C-domain in the center, and
      the E-domain at the carboxyl terminus. Like other synapsins, synapsin IIIa binds
      ATP with high affinity and ADP with a lower affinity, consistent with a cycle of
      ATP binding and hydrolysis. ATP binding to the different synapsins is directly
      regulated by Ca2+ in a dramatically different fashion: Ca2+ activates ATP binding
      to synapsin I, has no effect on synapsin II, and inhibits synapsin III. Thus
      vertebrates express three distinct synapsins that utilize ATP but are specialized
      for different modes of direct Ca2+ regulation in synaptic function.

PMID- 9593664
TI  - The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger,
      phosphatidylinositol 3,4,5-trisphosphate.
AB  - Phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) is a key molecule
      involved in cell growth signaling. We demonstrated that overexpression of PTEN, a
      putative tumor suppressor, reduced insulin-induced PtdIns(3,4,5)P3 production in
      human 293 cells without effecting insulin-induced phosphoinositide 3-kinase
      activation. Further, transfection of the catalytically inactive mutant of PTEN
      (C124S) caused PtdIns(3,4,5)P3 accumulation in the absence of insulin
      stimulation. Purified recombinant PTEN catalyzed dephosphorylation of
      PtdIns(3,4,5)P3, specifically at position 3 on the inositol ring. PTEN also
      exhibited 3-phosphatase activity toward inositol 1,3,4,5-tetrakisphosphate. Our
      results raise the possibility that PTEN acts in vivo as a phosphoinositide 3
      phosphatase by regulating PtdIns(3,4,5)P3 levels. As expected, the C124S mutant
      of PTEN was incapable of catalyzing dephosphorylation of PtdIns(3,4,5)P3
      consistent with the mechanism observed in protein-tyrosine phosphatase-catalyzed
      reactions.

PMID- 9593665
TI  - Amyloid beta protein-(1-42) forms calcium-permeable, Zn2+-sensitive channel.
AB  - Amyloid beta protein (AbetaP) forms senile plaques in the brain of the patients
      with Alzheimer's disease. The early-onset AD has been correlated with an
      increased level of 42-residue AbetaP (AbetaP1-42). However, very little is known
      about the role of AbetaP1-42 in such pathology. We have examined the activity of
      AbetaP1-42 reconstituted in phospholipid vesicles. Vesicles reconstituted with
      AbetaP show strong immunofluorescence labeling with an antibody raised against an
      extracellular domain of AbetaP suggesting the incorporation of AbetaP peptide in
      the vesicular membrane. Vesicles reconstituted with AbetaP showed a significant
      level of 45Ca2+ uptake. The 45Ca2+ uptake was inhibited by (i) a monoclonal
      antibody raised against the N-terminal region of AbetaP, (ii) Tris, and (iii)
      Zn2+. However, reducing agents Trolox and dithiothreitol did not inhibit the
      45Ca2+ uptake, indicating that the oxidation of AbetaP or its surrounding lipid
      molecules is not directly involved in the AbetaP-mediated Ca2+ uptake. An atomic
      force microscope was used to image the structure and physical properties of these
      vesicles. Vesicles ranged from 0.5 to 1 microm in diameter. The stiffness of the
      AbetaP-containing vesicles was significantly higher in the presence of calcium.
      The stiffness change was prevented in the presence of zinc, Tris, and anti-AbetaP
      antibody but not in the presence of Trolox and dithiothreitol. Thus the stiffness
      change is consistent with the vesicular uptake of Ca2+. These findings provide
      biochemical and structural evidence that AbetaP1-42 forms calcium-permeable
      channels and thus may induce cellular toxicity by regulating the calcium
      homeostasis in Alzheimer's disease.

PMID- 9593666
TI  - Nuclear opioid receptors activate opioid peptide gene transcription in isolated
      myocardial nuclei.
AB  - Opioid-binding sites were identified in highly purified nuclei isolated from
      hamster ventricular myocardial cells. A significant increase in the maximal
      binding capacity for a kappa opioid receptor ligand was observed in myocardial
      nuclei from BIO 14.6 cardiomyopathic hamsters, as compared with nuclei obtained
      from normal myocytes of the F1B strain. The exposure of isolated nuclei to
      dynorphin B, a natural agonist of kappa opioid receptors, markedly increased
      opioid peptide gene transcription. The transcriptional effect was mediated by
      nuclear protein kinase C activation and occurred at a higher rate in nuclei from
      cardiomyopathic myocytes than in nuclei isolated from normal cells. Thus, a
      nuclear endorphinergic system may play an intracrine role in the regulation of
      gene transcription under both normal and pathological conditions.

PMID- 9593667
TI  - Nuclear factor I regulates expression of the gene for phosphoenolpyruvate
      carboxykinase (GTP).
AB  - Nuclear factor-I (NFI) binds to the phosphoenolpyruvate carboxykinase (GTP)
      (PEPCK) gene promoter immediately 5' to the cAMP regulatory element (CRE). This
      suggests an interaction between NFI and factors that bind the CRE. Of the four
      NFI isoforms expressed in mammalian tissues, NFI-A and -B stimulate basal
      transcription from the PEPCK gene promoter in HepG2 cells, while NFI-C and -X are
      slightly inhibitory. All four NFI isoforms abrogate the 20-fold protein kinase Ac
      (PKAc)-mediated induction of transcription from the PEPCK gene promoter. Normal
      PKAc-mediated induction was noted when the CRE was moved 10 base pairs 3' of its
      original location. However if the CRE was moved 5 base pairs 3', placing it out
      of phase with the other elements in the promoter, or moved 5' to -285 (the P3(I)
      site in the promoter), some PKA-mediated stimulation was lost. The NFI-C isoform
      effectively inhibited PKAc induction regardless of the relative positions of the
      CRE and the NFI binding sites. NFI-C also abrogated cAMP regulatory element
      binding protein (CREB)-induced activity of wild type and mutant PEPCK promoters.
      There was some cooperativity in the binding of CREB and NFI to their respective
      binding sites but this did not appear to be physiologically important.

PMID- 9593668
TI  - Mutations in the activation function-2 core domain of steroidogenic factor-1
      dominantly suppresses PKA-dependent transactivation of the bovine CYP17 gene.
AB  - Steroidogenic factor-1 (SF-1) is a nuclear receptor that is essential for the
      proper development and function of steroid hormone-producing cells. The
      activation function-2 (AF-2) domain in SF-1 is a short alpha-helix in the C
      terminus that is conserved with respect to other nuclear receptors and is
      important for transactivation of target genes. In order to investigate the
      possible role of the AF-2 domain of SF-1 in cAMP-dependent transcriptional
      regulation of the bovine steroid hydroxylase gene CYP17, mutations were
      introduced and the effects were characterized. The mutant SF-1 proteins were
      expressed at comparable levels in nonsteroidogenic Cos-1 cells that lack SF-1,
      and their abilities to bind an SF-1 site from the CYP17 gene were not affected.
      Transient transfections of wild-type and mutant SF-1 in Cos-1 cells showed that
      the capacity to transactivate a reporter gene under the control of the SF-1 site
      from CYP17 was reduced by the mutations in the AF-2 domain of SF-1. A point
      mutation in the AF-2 region, E454A, resulted in a relative reporter gene activity
      that was 21% of that observed with wild-type SF-1. Co-transfections of
      adrenocortical Y-1 cells, which express endogenous SF-1, with the catalytic
      subunit of cAMP-dependent protein kinase (PKA-C) and the SF-1-dependent reporter
      gene showed on average a 16-fold increase in activity in the presence of PKA-C.
      Introduction of the AF-2 mutants of SF-1 into Y-1 cells completely abolished the
      PKA-C-mediated stimulation of the reporter gene. The transdominant negative
      effect of the mutant SF-1 proteins suggests that the AF-2 domain is essential for
      the activation of SF-1 by the cAMP-dependent protein kinase-dependent signaling
      pathway.

PMID- 9593669
TI  - Age-dependent modulation of heparan sulfate structure and function.
AB  - Heparan sulfate interacts with growth factors, matrix components, effectors and
      modulators of enzymatic catalysis as well as with microbial proteins via sulfated
      oligosaccharide domains. Although a number of such domains have been
      characterized, little is known about the regulation of their formation in vivo.
      Here we show that the structure of human aorta heparan sulfate is gradually
      modulated during aging in a manner that gives rise to markedly enhanced binding
      to isoforms of platelet-derived growth factor A and B chains containing polybasic
      cell retention sequences. By contrast, the binding to fibroblast growth factor 2
      is affected to a much lesser extent. The enhanced binding of aorta heparan
      sulfate to platelet-derived growth factor is suggested to be due to an age
      dependent increase of GlcN 6-O-sulfation, resulting in increased abundance of the
      trisulfated L-iduronic acid (2-OSO3)-GlcNSO3(6-OSO3) disaccharide unit. Such
      units have been shown to hallmark the platelet-derived growth factor A chain
      binding site in heparan sulfate.

PMID- 9593670
TI  - Binding of receptor-recognized forms of alpha2-macroglobulin to the alpha2
      macroglobulin signaling receptor activates phosphatidylinositol 3-kinase.
AB  - Ligation of the alpha2-macroglobulin (alpha2M) signaling receptor by receptor
      recognized forms of alpha2M (alpha2M*) initiates mitogenesis secondary to
      increased intracellular Ca2+. We report here that ligation of the alpha2M
      signaling receptor also causes a 1. 5-2.5-fold increase in wortmannin-sensitive
      phosphatidylinositol 3-kinase (PI3K) activity as measured by the quantitation of
      phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 formation was alpha2M*
      concentration-dependent with a maximal response at approximately 50 pM ligand
      concentration. The peak formation of PIP3 occurred at 10 min of incubation. The
      alpha2M receptor binding fragment mutant K1370R which binds to the alpha2M
      signaling receptor activating the signaling cascade, increased PIP3 formation by
      2-fold. The mutant K1374A, which binds very poorly to the alpha2M signaling
      receptor, did not cause any increase in PIP3 formation. alpha2M*-induced DNA
      synthesis was inhibited by wortmannin. 1, 2Bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acetoxymethylester a chelator of intracellular Ca2+, drastically
      reduced alpha2M*-induced increases in PIP3 formation. We conclude that PI3K is
      involved in alpha2M*-induced mitogenesis in macrophages and intracellular Ca2+
      plays a role in PI3K activation.

PMID- 9593671
TI  - Two regions of the ryanodine receptor involved in coupling with L-type Ca2+
      channels.
AB  - Ryanodine receptors (RyRs) are present in the endoplasmic reticulum of virtually
      every cell type and serve critical roles, including excitation-contraction (EC)
      coupling in muscle cells. In skeletal muscle the primary control of RyR-1 (the
      predominant skeletal RyR isoform) occurs via an interaction with plasmalemmal
      dihydropyridine receptors (DHPRs), which function as both voltage sensors for EC
      coupling and as L-type Ca2+ channels (Rios, E., and Brum, G. (1987) Nature 325,
      717-720). In addition to "receiving" the EC coupling signal from the DHPR, RyR-1
      also "transmits" a retrograde signal that enhances the Ca2+ channel activity of
      the DHPR (Nakai, J., Dirksen, R. T., Nguyen, H. T., Pessah, I. N., Beam, K. G.,
      and Allen, P. D. (1996) Nature 380, 72-76). A similar kind of retrograde
      signaling (from RyRs to L-type Ca2+ channels) has also been reported in neurons
      (Chavis, P., Fagni, L., Lansman, J. B., and Bockaert, J. (1996) Nature 382, 719
      722). To investigate the molecular mechanism of reciprocal signaling, we
      constructed cDNAs encoding chimeras of RyR-1 and RyR-2 (the predominant cardiac
      RyR isoform) and expressed them in dyspedic myotubes, which lack an endogenous
      RyR-1. We found that a chimera that contained residues 1,635-2,636 of RyR-1 both
      mediated skeletal-type EC coupling and enhanced Ca2+ channel function, whereas a
      chimera containing adjacent RyR-1 residues (2, 659-3,720) was only able to
      enhance Ca2+ channel function. These results demonstrate that two distinct
      regions are involved in the reciprocal interactions of RyR-1 with the skeletal
      DHPR.

PMID- 9593672
TI  - Ectopic epididymal expression of guinea pig intestinal phospholipase B. Possible
      role in sperm maturation and activation by limited proteolytic digestion.
AB  - Guinea pig intestinal phospholipase B is a calcium-independent phospholipase
      hydrolyzing sequentially the acyl ester bonds at sn-2 and sn-1 positions of
      glycerophospholipids, promoting the formation of sn-glycero-3-phosphocholine from
      phosphatidylcholine. This 140-kDa glycoprotein from the brush border membrane of
      differentiated enterocytes contributes to lipid digestion as an ectoenzyme. The
      cDNA coding for guinea pig phospholipase B was revealed to be the homologue of
      AdRab-B, an mRNA appearing in rabbit upon intestine development. The sequence
      predicts a polypeptide of 1463 amino acids displaying four homologous repeats,
      two of them containing the lipase consensus sequence GXSXG. A 5-kilobase
      transcript was particularly abundant in mature ileal and jejunal enterocytes but
      was also detected in epididymis, where phospholipase B displayed a higher
      molecular mass (170 kDa versus 140 kDa in intestine), with no obvious evidence
      for enzyme activity. Trypsin treatment of phospholipase B immunoprecipitated from
      epididymal membranes reduced its size to 140 kDa, coinciding with the appearance
      of a significant phospholipase A2 activity. The same results were obtained in COS
      cells transfected with phospholipase B cDNA. Since sn-glycero-3-phosphocholine
      present at high concentrations in seminal plasma mainly stems from epididymis,
      this suggests a possible role of phospholipase B in male reproduction. This novel
      localization also unravels a mechanism of phospholipase B activation by limited
      proteolysis involving either trypsin in the intestinal lumen or a trypsin-like
      endopeptidase in the male reproductive tract.

PMID- 9593674
TI  - Mild feline mucopolysaccharidosis type VI. Identification of an N
      acetylgalactosamine-4-sulfatase mutation causing instability and increased
      specific activity.
AB  - The missense mutation, L476P, in the N-acetylgalactosamine 4-sulfatase (4S) gene,
      has previously been shown to be associated with a severe feline
      mucopolysaccharidosis type VI (MPS VI) phenotype. The present study describes a
      second mutation, D520N, in the same MPS VI cat colony, which is inherited
      independently of L476P and is associated with a clinically mild MPS VI phenotype
      in D520N/L476P compound heterozygous cats. Biochemical and clinical assessment of
      L476P homozygous, D520N/L476P compound heterozygous, and D520N homozygous cats
      demonstrated that the entire range of clinical phenotypes, from severe MPS VI, to
      mild MPS VI, to normal are clustered within a narrow range of residual 4S
      activity from 0. 5% to 4.6% of normal levels. When overexpressed in CHO-KI cells,
      the secreted form of D520N 4S was inactivated in neutral pH conditions. In
      addition, intracellular D520N 4S protein was rapidly degraded and corresponded to
      37%, 14.5%, and 0.67% of normal 4S protein levels in the microsomal, endosomal,
      and lysosomal compartments, respectively. However, the specific activity of
      lysosomal D520N 4S was elevated 22. 5-fold when compared with wild-type 4S. These
      results suggest that the D520N mutation causes a rapid degradation of 4S protein.
      The effect of this is partially ameliorated as a result of a significant
      elevation in the specific activity of mutant D520N 4S reaching the lysosomal
      compartment.

PMID- 9593673
TI  - Ascorbate stimulates ferricyanide reduction in HL-60 cells through a mechanism
      distinct from the NADH-dependent plasma membrane reductase.
AB  - The impermeable oxidant ferricyanide is reduced by the plasma membrane redox
      system of HL-60 cells. The rate of reduction is strongly enhanced by ascorbate or
      dehydroascorbate. The aim of this study was to determine the mechanism by which
      ascorbate and dehydroascorbate accelerate ferricyanide reduction in HL-60 cells.
      Addition of ascorbate or dehydroascorbate to cells in the presence of
      ferricyanide led to the intracellular accumulation of ascorbate. Control
      experiments showed that extracellular ascorbate was rapidly converted to
      dehydroascorbate in the presence of ferricyanide. These data suggest that
      intracellular ascorbate originates from extracellular dehydroascorbate.
      Accumulation of ascorbate was prevented by inhibitors of dehydroascorbate
      transport into the cell. These compounds also strongly inhibited ascorbate
      stimulated ferricyanide reduction in HL-60 cells. Thus, it is concluded that the
      stimulation of ferricyanide reduction is dependent on intracellular accumulation
      of ascorbate. Changing the alpha-tocopherol content of the cells had no effect on
      the ascorbate-stimulated ferricyanide reduction, showing that a nonenzymatic
      redox system utilizing alpha-tocopherol was not involved. p
      Chloromercuribenzenesulfonic acid strongly affected ferricyanide reduction in the
      absence of ascorbate, whereas the stimulated reaction was much less responsive to
      this compound. Thus, it appears that at least two different membrane redox
      systems are operative in HL-60 cells, both capable of reducing ferricyanide, but
      through different mechanisms. The first system is the ferricyanide reductase,
      which uses NADH as its source for electrons, whereas the novel system proposed in
      this paper relies on ascorbate.

PMID- 9593675
TI  - Intracellular transport of the glycoproteins gE and gI of the varicella-zoster
      virus. gE accelerates the maturation of gI and determines its accumulation in the
      trans-Golgi network.
AB  - The varicella-zoster virus (VZV) is the etiological agent of two different human
      pathologies, chickenpox (varicella) and shingles (zoster). This alphaherpesvirus
      is believed to acquire its lipidic envelope in the trans-Golgi network (TGN).
      This is consistent with previous data showing that the most abundant VZV envelope
      glycoprotein gE accumulates at steady-state in this organelle when expressed from
      cloned cDNA. In the present study, we have investigated the intracellular
      trafficking of gI, another VZV envelope glycoprotein. In transfected cells, this
      protein shows a very slow biosynthetic transport to the cell surface where it
      accumulates. However, upon co-expression of gE, gI experiences a dramatic
      increase in its exit rate from the endoplasmic reticulum, it accumulates in a
      sialyltransferase-positive compartment, presumably the TGN, and cycles between
      this compartment and the cell surface. This differential behavior results from
      the ability of gE and gI to form a complex in the early stages of the
      biosynthetic pathway whose intracellular traffic is exclusively determined by the
      sorting information in the tail of gE. Thus, gI provides the first example of a
      molecule localized to the TGN by means of its association with another TGN
      protein. We also show that, during the early stages of VZV infection, both
      proteins are also found in the TGN of the host cell. This suggests the existence
      of an intermediate stage during VZV biogenesis in which the envelope
      glycoproteins, transiently arrested in the TGN, could promote the envelopment of
      newly synthesized nucleocapsids into this compartment and, therefore, the
      assembly of infective viruses.

PMID- 9593676
TI  - Negative feedback control of the retinoid-retinoic acid/retinoid X receptor
      pathway by the human TR4 orphan receptor, a member of the steroid receptor
      superfamily.
AB  - Amino acid sequence analysis indicates that the human TR4 orphan receptor (TR4)
      is a member of the estrogen/thyroid receptor subfamily of the steroid/thyroid
      receptor superfamily and recognizes the AGGTCA direct repeat (DR) of the hormone
      response element. Here we demonstrate using the electrophoretic mobility shift
      assay that TR4 binds specifically to DR with a spacing of 1 and 5 base pairs (DR1
      and DR5), which are the response elements for retinoic acid receptor (RAR) and
      retinoid X receptor (RXR), respectively. A reporter gene assay using
      chloramphenicol acetyltransferase demonstrated that TR4 repressed RA-induced
      transactivation in a TR4 dose-dependent manner. Inhibition of the retinoid signal
      pathway also occurs through natural response elements found in CRBPII and RARbeta
      genes. Our data suggest that the mechanism of repression may not involve the
      formation of functionally inactive heterodimers between TR4 and RAR or RXR.
      Instead, we show that TR4 may compete for hormone response elements with RAR and
      RXR due to its higher binding affinity. Furthermore, treatment of F9 murine
      teratocarcinoma (F9) cells with 10(-6) M all-trans-retinoic acid increased TR4
      mRNA levels, and this change was accompanied by an increased amount of endogenous
      TR4 protein that can bind to RXRE in electrophoretic mobility shift assay. Our
      data therefore strongly suggest that the retinoid signal pathway can be regulated
      by TR4 in a negative feedback control mechanism, which may restrict retinoic acid
      signaling to certain elements in a cell-specific fashion.

PMID- 9593677
TI  - Autocrine regulation of inducible nitric-oxide synthase in macrophages by atrial
      natriuretic peptide.
AB  - Atrial natriuretic peptide (ANP), a cardiovascular hormone, has been shown to
      inhibit synthesis of nitric oxide in lipopolysaccharide (LPS)-activated mouse
      bone marrow-derived macrophages via activation of its guanylate cyclase-coupled
      receptor. The goal of the present study was to elucidate the potential sites of
      inducible nitric-oxide synthase (iNOS) regulation affected by ANP and revealed
      the following. 1) ANP and dibutyryl-cGMP did not inhibit catalytic iNOS activity
      measured by the conversion rate of L-[3H]arginine to L-[3H]citrulline in
      homogenates of LPS-treated cells. 2) Pretreatment of cells with ANP dose
      dependently reduced the LPS-induced L-[3H]citrulline production that has been
      shown to be due to reduced iNOS protein levels detected by Western blot. 3) ANP
      does not alter the ratio of catalytically active iNOS dimer versus inactive iNOS
      monomer considered to be a major post-translational regulatory mechanism for the
      enzyme. 4) Macrophages exposed to ANP display decreased LPS-induced iNOS mRNA
      levels. 5) Importantly, two basic mechanisms seem to be responsible for this
      observation, i.e. ANP specifically induced acceleration of iNOS mRNA decay and
      ANP reduced binding activity of NF-kappaB, the transcription factor predominantly
      responsible for LPS-induced iNOS expression in murine macrophages. Moreover, 6)
      ANP acts via an autocrine mechanism since recently ANP was shown to be secreted
      by LPS-activated macrophages, and we demonstrated here that LPS-induced NO
      synthesis was increased after blocking the binding of endogenous ANP by a
      receptor antagonist. These observations suggest ANP as a new autocrine macrophage
      factor regulating NO synthesis both transcriptionally and post-transcriptionally.
      ANP may help to balance NO production of activated macrophages and thus may allow
      successful immune response without adverse effects on host cells.

PMID- 9593678
TI  - Differential cellular accumulation/retention of apolipoprotein E mediated by cell
      surface heparan sulfate proteoglycans. Apolipoproteins E3 and E2 greater than e4.
AB  - Isoform-specific effects of apolipoprotein E (apoE) on neurite outgrowth and the
      cytoskeleton are associated with higher intracellular levels of apoE3 than apoE4
      in cultured neurons. The current studies, designed to determine the mechanism for
      the differential intracellular accumulation or retention of apoE, demonstrate
      that apoE3- and apoE4-containing beta-very low density lipoproteins (beta-VLDL)
      possess similar cell binding and internalization and delivery of cholesterol to
      the cells. However, as assessed by immunocytochemistry, analysis of extracted
      cellular proteins, or quantitation of 125I-apoE-enriched beta-VLDL, there was a 2
      3-fold greater accumulation of apoE3 than apoE4 in Neuro-2a cells, fibroblasts,
      and hepatocytes (HepG2) after 1-2 h, and this differential was maintained for up
      to 48 h. ApoE2 also accumulated in Neuro-2a cells to a greater extent than apoE4.
      The differential effect was mediated by the apoE-enriched beta-VLDL and not by
      free apoE. Neither the low density lipoprotein receptor nor the low density
      lipoprotein receptor-related protein was responsible for the differential
      accumulation of apoE3 and apoE4, since cells deficient in either or both of these
      receptors also displayed the differential accumulation. The effect appears to be
      mediated primarily by cell surface heparan sulfate proteoglycans (HSPG). The
      retention of both apoE3 and apoE4 was markedly reduced, and the differential
      accumulation of apoE3 and apoE4 was eliminated both in mutant Chinese hamster
      ovary cells that did not express HSPG and in HSPG-expressing cells treated with
      heparinase. The data suggest that cell surface HSPG directly mediate the uptake
      of apoE-containing lipoproteins, that the differential accumulation/retention of
      apoE by cells is mediated via HSPG, and that there is a differential
      intracellular handling of the specific apoE isoforms.

PMID- 9593679
TI  - Identification of a novel growth factor-like lipid, 1-O-cis-alk-1'-enyl-2-lyso-sn
      glycero-3-phosphate (alkenyl-GP) that is present in commercial sphingolipid
      preparations.
AB  - Lysophosphatidic acid, a member of the acidic phospholipid autacoid (APA) family
      of lipid mediators, elicits diverse cellular effects that range from mitogenesis
      to the prevention of programmed cell death. Sphingosine 1-phosphate and
      sphingosylphosphorylcholine have also been proposed to be ligands of the APA
      receptors. However, key observations that provide the foundation of this
      hypothesis have not been universally reproducible, leading to a controversy in
      the field. We provide evidence that 1-O-cis-alk-1'-enyl-2-lyso-sn-glycero-3
      phosphate (alkenyl-GP) is present in some commercial sphingolipid preparations
      and is responsible for many of their APA-like effects, which were previously
      attributed to sphingosylphosphorylcholine. Alkenyl-GP was generated by acidic and
      basic methanolysis from ethanolamine lysoplasmalogen, which was present in the
      sphingomyelin fraction that is used to manufacture sphingosylphosphorylcholine.
      We present the structural identification of alkenyl-GP, using 1H and 13C NMR,
      Fourier transform infrared spectrometry, and mass spectrometry. Alkenyl-GP was a
      potent activator of the mitogen-activated protein kinases ERK1/2 and elicited a
      mitogenic response in Swiss 3T3 fibroblasts. In contrast,
      sphingosylphosphorylcholine at a concentration of 10 microM was only a weak
      mitogen and only weakly activated the extracellular signal-regulated protein
      kinases. Alkenyl-GP has recently been detected as an injury-induced component in
      the anterior chamber of the eye (Liliom, K., Guan, Z., Tseng, H., Desiderio, D.
      M., Tigyi, G., and Watsky, M. (1998) Am. J. Physiol. 274, C1065-C1074),
      indicating that this lipid is a naturally occurring member of the APA mediator
      family.

PMID- 9593680
TI  - Subunit stoichiometry of the epithelial sodium channel.
AB  - The epithelial Na+ Channel (ENaC) mediates Na+ reabsorption in a variety of
      epithelial tissues. ENaC is composed of three homologous subunits, termed alpha,
      beta, and gamma. All three subunits participate in channel formation as the
      absence of any one subunit results in a significant reduction or complete
      abrogation of Na+ current expression in Xenopus oocytes. To determine the subunit
      stoichiometry, a biophysical assay was employed utilizing mutant subunits that
      display significant differences in sensitivity to channel blockers from the wild
      type channel. Our results indicate that ENaC is a tetrameric channel with an
      alpha2 beta gamma stoichiometry, similar to that reported for other cation
      selective channels, such as Kv, Kir, as well as voltage-gated Na+ and Ca2+
      channels that have 4-fold internal symmetry.

PMID- 9593681
TI  - Modulation of white adipose tissue lipolysis by nitric oxide.
AB  - In isolated adipocytes, the nitrosothiols S-nitroso-N-acetyl-penicillamine (SNAP)
      and S-nitrosoglutathione stimulate basal lipolysis, whereas the nitric oxide
      (NO.) donor 1-propamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazine) (PAPA-NONOate)
      or NO gas have no effect. The increase in basal lipolysis due to nitrosothiols
      was prevented by dithiothreitol but not by a guanylate cyclase inhibitor. In
      addition the cyclic GMP-inhibited low Km, cyclic AMP phosphodiesterase activity
      was inhibited by SNAP suggesting that SNAP acting as NO+ donor increases basal
      lipolysis through a S-nitrosylation mediated inhibition of phosphodiesterase.
      Contrasting with these findings, SNAP reduced both isoproterenol-stimulated
      lipolysis and cyclic AMP production, whereas it failed to modify forskolin-,
      dibutyryl cyclic AMP-, or isobutylmethylxanthine-stimulated lipolysis, suggesting
      that SNAP interferes with the beta-adrenergic signal transduction pathway
      upstream the adenylate cyclase. In contrast with SNAP, PAPA-NONOate or NO gas
      inhibited stimulated lipolysis whatever the stimulating agents used without
      altering cyclic AMP production. Moreover PAPA-NONOate slightly reduces (30%) the
      hormone-sensitive lipase (HSL) activity indicating that stimulated lipolysis
      inhibition by NO. is linked to both inhibition of the HSL activity and the cyclic
      AMP-dependent activation of HSL. These data suggest that NO. or related redox
      species like NO+/NO- are potential regulators of lipolysis through distinct
      mechanisms.

PMID- 9593682
TI  - Scanning alanine mutagenesis of the CDP-alcohol phosphotransferase motif of
      Saccharomyces cerevisiae cholinephosphotransferase.
AB  - Cholinephosphotransferase (EC 2.7.8.2) catalyzes the formation of a phosphoester
      bond via the transfer of a phosphocholine moiety from CDP-choline to
      diacylglycerol forming phosphatidylcholine and releasing CMP. A motif, Asp113
      Gly114-(X)2-Ala117-Arg118-(X)8-Gly127+ ++-(X)3-Asp131-(X)3-Asp135, located within
      the CDP-choline binding region of Saccharomyces cerevisiae
      cholinephosphotransferase (CPT1 ?/Author: Please confirm that a gene is meant
      here.) is also found in several other phospholipid synthesizing enzymes that
      catalyze the formation of a phosphoester bond utilizing a CDP-alcohol and a
      second alcohol as substrates. To determine if this motif is diagnostic of the
      above reaction type scanning alanine mutagenesis of the conserved residues within
      S. cerevisiae cholinephosphotransferase was performed. Enzyme activity was
      assessed in vitro using a mixed micelle enzyme assay and in vivo by determining
      the ability of the mutant enzymes to restore phosphatidylcholine synthesis from
      radiolabeled choline in an S. cerevisiae strain devoid of endogenous
      cholinephosphotransferase activity. Alanine mutants of Gly114, Gly127, Asp131,
      and Asp135 were inactive; mutants, Ala117 and Arg118 displayed reduced enzyme
      activity, and Asp113 displayed wild type activity. The analysis described is the
      first molecular characterization of a CDP-alcohol phosphotransferase motif and
      results predict a catalytic role utilizing a general base reaction proceeding
      through Asp131 or Asp135 via a direct nucleophilic attack of the hydroxyl of
      diacylglyerol on the phosphoester bond of CDP-choline that does not proceed via
      an enzyme bound intermediate. Residues Ala117 and Arg118 do not participate
      directly in catalysis but are likely involved in substrate binding or positioning
      with Arg118 predicted to associate with a phosphate moiety of CDP-choline.

PMID- 9593683
TI  - Interaction of cysteine string proteins with the alpha1A subunit of the P/Q-type
      calcium channel.
AB  - Cysteine string proteins (Csps) are J-domain chaperone proteins anchored at the
      surface of synaptic vesicles. Csps are involved in neurotransmitter release and
      may modulate presynaptic calcium channel activity, although the molecular
      mechanisms are unknown. Interactions between Csps, proteins of the synaptic core
      (SNARE) complex, and P/Q-type calcium channels were therefore explored. Co
      immunoprecipitation suggested that Csps occur in complexes containing
      synaptobrevin (VAMP), but not syntaxin 1, SNAP-25, nor P/Q-type calcium channels
      labeled with 125I-omega-conotoxin MVIIC. However binding experiments with 35S
      labeled Csp1 demonstrated an interaction (apparent KD = 700 nM at pH 7.4 and 4
      degreesC) with a fusion protein containing a segment of the cytoplasmic loop
      linking homologous domains II-III of the alpha1A calcium channel subunit (BI
      isoform, residues 780-969). Binding was specific as it was displaced by unlabeled
      Csp1, and no interactions were detected with fusion proteins containing other
      calcium channel domains, VAMP, or syntaxin 1A. A Csp binding site on the P/Q-type
      calcium channel is thus located within the 200 residue synaptic protein
      interaction site that can also bind syntaxin I, SNAP-25, and synaptotagmin I. Csp
      may act as a molecular chaperone to direct assembly or disassembly of exocytotic
      complexes at the calcium channel.

PMID- 9593685
TI  - Reaction of neuronal nitric-oxide synthase with oxygen at low temperature.
      Evidence for reductive activation of the oxy-ferrous complex by
      tetrahydrobiopterin.
AB  - The reaction of reduced NO synthase (NOS) with molecular oxygen was studied at 
      30 degreesC. In the absence of substrate, the complex formed between ferrous NOS
      and O2 was sufficiently long lived for a precise spectroscopic characterization.
      This complex displayed similar spectral characteristics as the oxyferrous complex
      of cytochrome P450 (lambda max = 416.5 nm). It then decomposed to the ferric
      state. The oxidation of the flavin components was much slower and could be
      observed only at temperatures higher than -20 degreesC. In the presence of
      substrate (L-arginine), another, 12-nm blue-shifted, intermediate spectrum was
      formed. The breakdown of the latter species resulted in the production of Nomega
      hydroxy-L-arginine in a stoichiometry of maximally 52% per NOS heme. This product
      formation took place also in the absence of the reductase domain of NOS. Both
      formation of the blue-shifted intermediate and of Nomega-hydroxy-L-arginine
      required the presence of tetrahydrobiopterin (BH4). We propose that the blue
      shifted intermediate is the result of reductive activation of the oxygenated
      complex, and the electron is provided by BH4. These observations suggest that the
      reduction of the oxyferroheme complex may be the main function of BH4 in NOS
      catalysis.

PMID- 9593684
TI  - C/EBPepsilon is a myeloid-specific activator of cytokine, chemokine, and
      macrophage-colony-stimulating factor receptor genes.
AB  - C/EBPepsilon is a member of the CCAAT/enhancer binding protein family of basic
      region/leucine zipper transcriptional activators. The C/EBPepsilon protein is
      highly conserved between rodents and humans, and its domain structure is very
      similar to C/EBPalpha. In mice C/EBPepsilon mRNA is only detected in
      hematopoietic tissues, including embryonic liver and adult bone marrow and
      spleen. Within the hematopoietic system, C/EBPepsilon is expressed primarily in
      myeloid cells, including promyelocytes, myelomonocytes, and their differentiated
      progeny. To identify potential functions of C/EBPepsilon, cell lines over
      expressing the C/EBPepsilon protein were generated in the P388 lymphoblastic cell
      line. In contrast to the parental cell line, C/EBPepsilon-expressing cell lines
      displayed lipopolysaccharide-inducible expression of the interleukin-6 and
      monocyte chemoattractant protein 1 (MCP-1) genes as well as elevated basal
      expression of the MIP-1alpha and MIP-1beta chemokine genes. In the EML-C1
      hematopoietic stem cell line, C/EBPepsilon mRNA levels increased as the cells
      progressed along the myeloid lineage, just preceding activation of the gene
      encoding the receptor for macrophage-colony-stimulating factor (M-CSFR). M-CSFR
      expression was stimulated in C/EBPepsilon-expressing P388 cell lines, when
      compared with either the parental P388 cells or P388 cell lines expressing either
      C/EBPalpha or C/EBPbeta. These results suggest that C/EBPepsilon may be an
      important regulator of differentiation of a subset of myeloid cell types and may
      also participate in the regulation of cytokine gene expression in mature cells.

PMID- 9593686
TI  - Stage-specific proteophosphoglycan from Leishmania mexicana amastigotes.
      Structural characterization of novel mono-, di-, and triphosphorylated
      phosphodiester-linked oligosaccharides.
AB  - Intracellular amastigotes of the protozoan parasite Leishmania mexicana secrete a
      macromolecular proteophosphoglycan (aPPG) into the phagolysosome of their host
      cell, the mammalian macrophage. The structures of aPPG glycans were analyzed by a
      combination of high pH anion exchange high pressure liquid chromatography, gas
      chromatography-mass spectrometry, enzymatic digestions, electrospray-mass
      spectrometry as well as 1H and 31P NMR spectroscopy. Some glycans are identical
      to oligosaccharides known from Leishmania mexicana promastigote lipophosphoglycan
      and secreted acid phosphatase. However, the majority of the aPPG glycans
      represent amastigote stage-specific and novel structures. These include neutral
      glycans ([Glcbeta1-3]1-2Galbeta1-4Man, Galbeta1-3Galbeta1-4Man, Galbeta1
      3Glcbeta1-3Galbeta1-4Man), several monophosphorylated glycans containing the
      conserved phosphodisaccharide backbone (R-3-[PO4-6-Gal]beta1-4Man) but carrying
      stage-specific modifications (R = Galbeta1-, [Glcbeta1-3]1-2Glcbeta1-), and
      monophosphorylated aPPG tri- and tetrasaccharides that are uniquely
      phosphorylated on the terminal hexose (PO4-6-Glcbeta1-3Galbeta1-4Man, PO4-6
      Glcbeta1-3Glcbeta1-3Galbeta1-4Man, PO4-6-Galbeta1-3Glcbeta1-3Galbeta1-4Man). In
      addition aPPG contains highly unusual di- and triphosphorylated glycans whose
      major species are PO4-6-Glcbeta1-3Glcbeta1-3[PO4-6-Gal]beta1-4Man, PO4-6-Galbeta1
      3Glcbeta1-3[PO4-6-Gal]beta1-4Man, PO4-6-Galbeta1-3Glcbeta1-3Glcbeta1-3[PO4-6
      Gal]beta1-+ ++4Man, PO4-6-Glcbeta1-3[PO4-6-Glc]beta1-3[PO4-6-Gal]beta1-4Man, PO4
      6-Galbeta1-3[PO4-6-Glc]beta1-3Glcbeta1-3[PO4-6-Gal]beta1 -4Man, and PO4-6
      Glcbeta1-3[PO4-6-Glc]beta1-3Glcbeta1-3[PO4-6-Gal]beta1 -4Man. These glycans are
      linked together by the conserved phosphodiester R-Manalpha1-PO4-6-Gal-R or the
      novel phosphodiester R-Manalpha1-PO4-6-Glc-R and are connected to Ser(P) of the
      protein backbone most likely via the linkage R-Manalpha1-PO4-Ser. The variety of
      stage-specific glycan structures in Leishmania mexicana aPPG suggests the
      presence of developmentally regulated amastigote glycosyltransferases which may
      be potential anti-parasite drug targets.

PMID- 9593687
TI  - Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis.
AB  - The onset of apoptosis is coupled to the proteolytic activation of a family of
      cysteine proteases, termed caspases. These proteases cleave their target proteins
      after an aspartate residue. Following caspase activation during apoptosis, a
      number of specific proteins have been shown to be cleaved. Here we show that
      Nedd4, a ubiquitin-protein ligase containing multiple WW domains and a
      calcium/lipid-binding domain, is also cleaved during apoptosis induced by a
      variety of stimuli including Fas-ligation, gamma-radiation, tumor necrosis factor
      alpha, C-8 ceramide, and etoposide treatment. Extracts from apoptotic cells also
      generated cleavage patterns similar to that seen in vivo, and this cleavage was
      inhibited by an inhibitor of caspase-3-like proteases. In vitro, Nedd4 was
      cleaved by a number of caspases, including caspase-1, -3, -6, and -7. By site
      directed mutagenesis, one of the in vitro caspase cleavage sites in mouse Nedd4
      was mapped to a DQPD237 downward arrow sequence, which is conserved between
      mouse, rat, and human proteins. This is the first report demonstrating that an
      enzyme of the ubiquitin pathway is cleaved by caspases during apoptosis.

PMID- 9593688
TI  - Glucocorticoid regulation of calcium-activated potassium channels mediated by
      serine/threonine protein phosphatase.
AB  - Adrenal glucocorticoids exert powerful effects on cellular excitability in
      neuroendocrine cells and neurons, although the underlying mechanisms are poorly
      understood. In metabolically intact mouse anterior pituitary corticotrope (AtT20)
      cells glucocorticoid-induced proteins render large conductance calcium-activated
      potassium (BK) channels insensitive to inhibition by protein kinase A (PKA). In
      this study we have addressed whether this action of glucocorticoids is mediated
      via protein phosphatase activity at the level of single BK channels. In isolated
      inside-out patches from control AtT20 cells BK channels (125 pS) were inhibited
      by activation of closely associated PKA. Pretreatment (2 h) of cells with 1
      microM dexamethasone before patch excision did not modify the intrinsic
      properties or expression levels of BK channel alpha-subunits in AtT20 cells.
      However, PKA-mediated inhibition of BK channel activity in isolated patches from
      steroid-treated cells was severely blunted. This effect of steroid was not
      observed using adenosine 5'-O-(3-thiotriphosphate) as phosphate donor or on
      exposure of the intracellular face of the patch with 10 nM of the protein
      phosphatase inhibitors okadaic acid or calyculin A but was mimicked by
      application of protein phosphatase 2A (PP2A) to the intracellular face of patches
      from control cells. Glucocorticoids did not modify total PP2A activity in AtT20
      cells, suggesting that modified PP2A-like phosphatase activity closely associated
      with BK channels is required for glucocorticoid action.

PMID- 9593689
TI  - Identification of an alpha helical motif sufficient for association with
      papillomavirus E6.
AB  - We recently identified a cellular protein named E6BP or ERC-55 that binds cancer
      related papillomavirus E6 proteins (Chen, J. J., Reid, C. E., Band, V., and
      Androphy, E. J. (1995) Science 269, 529-531). By construction of a series of
      deletion mutants, the region of E6BP that is necessary and sufficient for complex
      formation with human papillomavirus type 16 E6 has been mapped to a 25-amino acid
      domain. The corresponding peptide was synthesized and found by nuclear magnetic
      resonance spectroscopy to bind calcium and fold into a classical helix-loop-helix
      EF-hand conformation. Additional deletion mutagenesis showed that 13 amino acids
      that form the second alpha helix mediated E6 association. Alanine replacement
      mutagenesis indicated that amino acids of this helix were most important for E6
      binding. Alignment of this alpha helical E6 binding peptide with the 18-amino
      acid E6 binding region of E6AP (Huibregtse, J. M., Scheffner, M., and Howley, P.
      M. (1993) Mol. Cell. Biol. 13, 4918-4927) and the first LD repeat of another E6
      binding protein, paxillin (Tong, X., and Howley, P. M. (1997) J. Biol. Chem. 272,
      33373-33376), revealed substantial similarities among these E6 binding domains.
      The extent of homology and the mutational data define the peptide as an E6
      binding motif.

PMID- 9593690
TI  - Induction of matrix metalloproteinase-9 requires a polymerized actin cytoskeleton
      in human malignant glioma cells.
AB  - Alterations in cytoskeleton and subsequent cell shape changes exert specific
      effects on the expression of various genes. Our previous results suggested that
      malignant human gliomas express elevated levels of matrix metalloproteinases
      compared with normal brain tissue and low grade gliomas. To understand the role
      of cell shape changes on matrix metalloproteinase expression in human glioma
      cells, we treated SNB19 cells with cytochalasin-D, an inhibitor of actin
      polymerization, and colchicine-B, a tubulin inhibitor, in the presence of phorbol
      12-myristate 13-acetate. Cytochalasin-D treatment of SNB19 cells resulted in the
      loss of phorbol 12-myristate 13-acetate-induced matrix metalloproteinase-9 (also
      known as gelatinase-B) expression and coincided with inhibition of actin
      polymerization, resulting in cell rounding. Moreover, compared with monolayers,
      cells grown as spheroids or cell aggregates failed to express matrix
      metalloproteinase-9 in the presence of phorbol 12-myristate 13-acetate. Matrix
      metalloproteinase-9 expression was also inhibited by calphostin-C, a protein
      kinase inhibitor, suggesting the involvement of protein kinase C in matrix
      metalloproteinase-9 expression. Phorbol 12-myristate 13-acetate-induced invasion
      of SNB19 cells through Matrigel was inhibited by cytochalasin-D and calphostin-C.
      These results suggest that the actin polymerization transduces signals that
      modulate the expression of matrix metalloproteinase-9 expression and the
      subsequent invasion of human glioma cells.

PMID- 9593691
TI  - Isoforms of hepatocyte nuclear factor-6 differ in DNA-binding properties, contain
      a bifunctional homeodomain, and define the new ONECUT class of homeodomain
      proteins.
AB  - Hepatocyte nuclear factor-6 (HNF-6) contains a single cut domain and a
      homeodomain characterized by a phenylalanine at position 48 and a methionine at
      position 50. We describe here two isoforms of HNF-6 which differ by the linker
      that separates these domains. Both isoforms stimulated transcription. The
      affinity of HNF-6alpha and HNF-6beta for DNA differed, depending on the target
      sequence. Binding of HNF-6 to DNA involved the cut domain and the homeodomain,
      but the latter was not required for binding to a subset of sites. Mutations of
      the F48M50 dyad that did not affect DNA binding reduced the transcriptional
      stimulation of constructs that do not require the homeodomain for DNA binding,
      but did not affect the stimulation of constructs that do require the homeodomain.
      Comparative trees of mammalian, Drosophila, and Caenorhabditis elegans proteins
      showed that HNF-6 defines a new class, which we call ONECUT, of homeodomain
      proteins. C. elegans proteins of this class bound to HNF-6 DNA targets. Thus,
      depending on their sequence, these targets determine for HNF-6 at least two modes
      of DNA binding, which hinge on the homeodomain and on the linker that separates
      it from the cut domain, and two modes of transcriptional stimulation, which hinge
      on the homeodomain.

PMID- 9593692
TI  - Interaction of secretory leukocyte protease inhibitor with heparin inhibits
      proteases involved in asthma.
AB  - Protease inhibition by secretory leukocyte protease inhibitor (SLPI) is
      accelerated by the sulfated polysaccharides. The nature of the SLPI
      polysaccharide interaction, explored with affinity chromatography, indicated that
      this interaction was sensitive to the charge and type of polysaccharide. Dextran
      and chondroitin had the lowest affinity for SLPI, followed by dermatan, heparan,
      and dextran sulfates. While heparin bound SLPI tightly, the highest affinity
      heparin chains unexpectedly contained a lower level of sulfation than more weakly
      interacting chains. Heparin oligosaccharides, prepared using heparin lyase I were
      SLPI-affinity fractionated. Surprisingly, undersulfated heparin oligosaccharides
      bound SLPI with the highest affinity, suggesting the importance of free hydroxyl
      groups for high affinity interaction. Isothermal titration calorimetry was used
      to determine the thermodynamics of SLPI interaction with a low molecular weight
      heparin, an undersulfated decasaccharide and a tetrasaccharide. The studies
      showed 12-14 saccharide units, corresponding to molecular weight of approximately
      4,800, were required for a 1:1 (SLPI:heparin) binding stoichiometry. Furthermore,
      an undersulfated decasaccharide was able to bind SLPI tightly (Kd approximately
      13 nM), resulting in its activation and the inhibition of neutrophil elastase and
      pancreatic chymotrypsin. The in vitro assessment of heparin and the
      decasaccharide and tetrasaccharide using stopped-flow kinetics suggested that
      heparin was the optimal choice to study SLPI-based in vivo protease inhibition.
      SLPI and heparin were co-administered by inhalation in therapy against antigen
      induced airway hyperresponsiveness in a sheep bronchoprovocation model. Heparin,
      in combination with SLPI demonstrated in vivo efficacy reducing early and late
      phase bronchoconstriction. Heparin also increased the therapeutic activity of
      SLPI against antigen-induced airway hyperresponsiveness.

PMID- 9593693
TI  - Purification, cDNA cloning, and expression of UDP-Gal: glucosylceramide beta-1,4
      galactosyltransferase from rat brain.
AB  - Lactosylceramide synthase is an enzyme that catalyzes the transfer of galactose
      from UDP-Gal to glucosylceramide, and thus participates in the biosynthesis of
      most glycosphingolipids in mammals. We purified this enzyme over 61,000-fold to
      near homogeneity with a 29. 7% yield from rat brain membrane fractions. The
      isolation procedure included solubilization with Triton X-100, affinity
      chromatography on wheat germ agglutinin-agarose and UDP-hexanolamine-agarose, and
      hydroxylapatite column chromatography, followed by ion exchange chromatography.
      The final preparation migrated as a broad band with an apparent molecular mass of
      61 kDa on SDS-polyacrylamide gel electrophoresis. This apparent molecular mass
      was reduced to 51 kDa by N-glycanase digestion, suggesting that the enzyme has a
      glycoprotein nature. The enzyme required Mn2+ for its activity, and
      glucosylceramide was its preferred substrate. The cDNA for the enzyme was cloned
      from a rat brain cDNA library. The cDNA insert encoded a polypeptide of 382 amino
      acid residues, with a molecular weight of 44,776. The polypeptide contained eight
      putative glycosylation sites and a 20-amino acid residue transmembrane domain at
      its N terminus. Amino acid sequence homology analysis revealed that this enzyme
      shared 39% homology with mouse beta-1, 4-galactosyltransferase (EC 2.4.1.38),
      which catalyzes the transfer of Gal to beta-1,4-GlcNAc in glycoproteins.

PMID- 9593694
TI  - State-dependent inhibition of the mitochondrial KATP channel by glyburide and 5
      hydroxydecanoate.
AB  - The mitochondrial KATP channel (mitoKATP) is hypothesized to be the receptor for
      the cardioprotective effects of K+ channel openers (KCO) and for the blocking of
      cardioprotection by glyburide and 5-hydroxydecanoate (5-HD). Studies on glyburide
      have indicated that this drug is inactive in isolated mitochondria. No studies of
      the effects of 5-HD on isolated mitochondria have been reported. This paper
      examines the effects of glyburide and 5-HD on K+ flux in isolated, respiring
      mitochondria. We show that mitoKATP is completely insensitive to glyburide and 5
      HD under the experimental conditions in which the open state of the channel is
      induced by the absence of ATP and Mg2+. On the other hand, mitoKATP became highly
      sensitive to glyburide and 5-HD when the open state was induced by Mg2+, ATP, and
      a physiological opener, such as GTP, or a pharmacological opener, such as
      diazoxide. In these open states, glyburide (K1/2 values 1-6 microM) and 5-HD
      (K1/2 values 45-75 microM) inhibited specific, mitoKATP-mediated K+ flux in both
      heart and liver mitochondria from rat. These results are consistent with a role
      for mitoKATP in cardioprotection and show that different open states of mitoKATP,
      although catalyzing identical K+ fluxes, exhibit very different susceptibilities
      to channel inhibitors.

PMID- 9593695
TI  - Characterization of the myoglobin and its coding gene of the mollusc Biomphalaria
      glabrata.
AB  - A cDNA clone isolated from a Biomphalaria glabrata (Mollusca, Gastropoda) neural
      cDNA library was identified as encoding a myoglobin-like protein of 148 amino
      acids with a single domain and a calculated mass of 16,049.29. Alignment with
      globin sequences with known tertiary structure confirms its overall globin
      nature. The expressed myoglobin was identified in the radular muscle and
      isolated. Oxygen equilibrium measurements on the protein reveal a high oxygen
      affinity. Val-B10 and Gln-E7, important residues for the determination of the
      oxygen affinity, are strikingly different from the standard molluscan pattern
      (Conti, E., Moser, C., Rizzi, M., Mattevi, A., Lionetti, C., Coda, A., Ascenzi,
      P., Brunori, M., Bolognesi, M. (1993) J. Mol. Biol. 233, 498-508). The single
      gene encoding the globin chain is interrupted by three introns at positions A3.2,
      B12.2, and G7.0. Comparison with other nonvertebrate globin genes reveals on the
      one hand conservation (B12.2 and G7.0) and on the other hand variability of the
      insertion positions (A3.2). The Biomphalaria myoglobin sequence was used together
      with all other molluscan globin sequences available to assess the origin and
      phylogeny of the phylum. Our results confirm the doubts raised about monophyletic
      origin of the Mollusca, which was first observed using SSU rRNA as a molecular
      marker.

PMID- 9593696
TI  - Maximal activity of an erythroid-specific enhancer requires the presence of
      specific protein binding sites in linked promoters.
AB  - High level expression of many eukaryotic genes is achieved through the action of
      distal regulatory sequences or enhancers. We have utilized the interaction
      between the erythroid-specific enhancer in hypersensitivity site 2 (HS2) of the
      human beta-globin locus control region and the globin gene promoters as a model
      to elucidate the mechanisms governing promoter/enhancer interactions. HS2
      contains a 400-base pair core element consisting of tandem AP1/NF-E2 motifs
      flanked by binding sites for multiple ubiquitous and erythroid-specific factors.
      We have compared the enhancer activity of this core element with a synthetic
      enhancer lacking the factor binding sites flanking the AP1/NF-E2 motif (HS2(M)).
      In fetal/erythroid K562 cells, enhancement of a linked gamma-promoter was
      significantly greater with wild-type HS2 than with HS2(M). In contrast, the
      increase in beta-promoter activity in these cells was equivalent with either
      enhancer fragment. Truncation of the binding site for the fetal/erythroid
      specific stage selector protein in the gamma-promoter abolished the additional
      enhancer activity of HS2. Similarly, insertion of the stage selector protein site
      into the beta-promoter boosted enhancer activity observed with HS2 but not
      HS2(M). In adult erythroid MEL cells, enhancement of a linked beta-promoter was
      significantly greater with HS2 than with HS2(M). This effect was dependent on the
      binding of the adult stage-specific factor, erythroid Kruppel-like factor, to the
      beta-promoter. Taken together, this data suggests that the stage-specific factors
      binding the proximal globin promoters and the factors flanking the AP1/NF-E2
      motif of HS2 act in synergy.

PMID- 9593697
TI  - Lack of transcription-coupled repair of acetylaminofluorene DNA adducts in human
      fibroblasts contrasts their efficient inhibition of transcription.
AB  - The N-(deoxyguanosine-8-yl)-2-acetylaminofluorene (dG-C8-AAF) lesion is among the
      most helix distorting DNA lesions. In normal fibroblasts dG-C8-AAF is repaired
      rapidly in transcriptionally active genes, but without strand specificity,
      indicating that repair of dG-C8-AAF by global genome repair (GGR) overrules
      transcription-coupled repair (TCR). Yet, dG-C8-AAF is a very potent inhibitor of
      transcription. The target size of inhibition (45 kilobases) suggests that
      transcription inhibition by dG-C8-AAF is caused by blockage of initiation rather
      than elongation. Cockayne's syndrome (CS) cells appear to be extremely sensitive
      to the cytotoxic effects of dG-C8-AAF and are unable to recover inhibited RNA
      synthesis. However, CS cells exhibit no detectable defect in repair of dG-C8-AAF
      in active genes, indicating that impaired TCR is not the cause of the enhanced
      sensitivity of CS cells. These and data reported previously suggest that the
      degree of DNA helix distortion determines the rate of GGR as well as the extent
      of inhibition of transcription initiation. An interchange of the
      transcription/repair factor TFIIH from promoter sites to sites of damage might
      underlie inhibition of transcription initiation. This process is likely to occur
      more rapidly and efficiently in the case of strongly DNA helix distorting
      lesions, resulting in a very efficient GGR, a poor contribution of TCR to repair
      of lesions in active genes, and an efficient inhibition of transcription.

PMID- 9593698
TI  - Formation of isoprostane-like compounds (neuroprostanes) in vivo from
      docosahexaenoic acid.
AB  - F2-isoprostanes are prostaglandin F2-like compounds that are formed
      nonenzymatically by free radical-induced oxidation of arachidonic acid. We
      explored whether oxidation of docosahexaenoic acid (C22:6omega3), which is highly
      enriched in the brain, led to the formation of F2-isoprostane-like compounds,
      which we term F4-neuroprostanes. Oxidation of docosahexaenoic acid in vitro
      yielded a series of compounds that were structurally established to be F4
      neuroprostanes using a number of mass spectrometric approaches. The amounts
      formed exceeded levels of F2-isoprostanes generated from arachidonic acid by 3.4
      fold. F4-neuroprostanes were detected esterified in normal whole rat brain and
      newborn pig cortex at a level of 7.0 +/- 1.4 ng/g and 13.1 +/- 8 ng/g,
      respectively. Furthermore, F4-neuroprostanes could be detected in normal human
      cerebrospinal fluid and levels in patients with Alzheimer's disease (110 +/- 12
      pg/ml) were significantly higher than age-matched controls (64 +/- 8 pg/ml) (p <
      0.05). F4-neuroprostanes may provide a unique marker of oxidative injury to the
      brain and could potentially exert biological activity. Furthermore, the formation
      of F4-neuroprostane-containing aminophospholipids might adversely effect neuronal
      function as a result of alterations they induce in the biophysical properties of
      neuronal membranes.

PMID- 9593699
TI  - Ability of various bombesin receptor agonists and antagonists to alter
      intracellular signaling of the human orphan receptor BRS-3.
AB  - Bombesin (Bn) receptor subtype 3 (BRS-3) is an orphan receptor that is a
      predicted member of the heptahelical G-protein receptor family and so named
      because it shares a 50% amino acid homology with receptors for the mammalian
      bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide. In a
      recent targeted disruption study, in which BRS-3-deficient mice were generated,
      the mice developed obesity, diabetes, and hypertension. To date, BRS-3's natural
      ligand remains unknown, its pharmacology unclear, and cellular basis of action
      undetermined. Furthermore, there are few tissues or cell lines found that express
      sufficient levels of BRS-3 protein for study. To define the intracellular
      signaling properties of BRS-3, we examined the ability of [D-Phe6,beta
      Ala11,Phe13, Nle14]Bn-(6-14), a newly discovered peptide with high affinity for
      BRS-3, and various Bn receptor agonists and antagonists to alter cellular
      function in hBRS-3-transfected BALB 3T3 cells and hBRS-3-transfected NCI-H1299
      non-small cell lung cancer cells, which natively express very low levels of hBRS
      3. This ligand stimulated a 4-9-fold increase in [3H]inositol phosphate formation
      in both cell lines under conditions where it caused no stimulation in
      untransfected cells and also stimulated an increase in [3H]IP1, [3H]IP2, and
      3H]IP3. The elevation of [3H]IP was concentration-dependent, with an EC50 of 20
      35 nM in both cell lines. [D-Phe6,beta-Ala11,Phe13,Nle14]Bn-(6-14) stimulated a 2
      3-fold increase in [Ca2+]i, a 3-fold increase in tyrosine phosphorylation of
      p125(FAK) with an EC50 of 0.2-0.7 nM, but failed to either stimulate increases in
      cyclic AMP or inhibit forskolin-stimulated increases. None of nine naturally
      occurring Bn peptides or three synthetic Bn analogues reported to activate hBRS-3
      did so with high affinity. No high affinity Bn receptor antagonists had high
      affinity for the hBRS-3 receptor, although two low affinity antagonists for
      gastrin-releasing peptide and NMB receptors, [D-Arg1,D-Trp7,9, Leu11]substance P
      and [D-Pro4,D-Trp7,9,10]substance P-(4-11), inhibited hBRS-3 receptor activation.
      The NMB receptor-specific antagonist D-Nal,Cys,Tyr,D-Trp,Lys,Val, Cys,Nal-NH2
      inhibited hBRS-3 receptor activation in a competitive fashion (Ki = 0.5 microM).
      Stimulation of p125(FAK) tyrosine phosphorylation by hBRS-3 activation was not
      inhibited by the protein kinase C inhibitor, GF109203X, or thapsigargin, alone or
      in combination. These results show that hBRS-3 receptor activation increases
      phospholipase C activity, which causes generation of inositol phosphates and
      changes in [Ca2+]i and is also coupled to tyrosine kinase activation, but is not
      coupled to adenylate cyclase activation or inhibition. hBRS-3 receptor activation
      results in tyrosine phosphorylation of p125(FAK), and it is not dependent on
      activation of either limb of the phospholipase C cascade. Although the natural
      ligand is not a known bombesin-related peptide, the availability of [D-Phe6,beta
      Ala11, Phe13,Nle14]Bn-(6-14), which functions as a high affinity agonist in
      conjunction with hBRS-3-transfected cell lines and the recognition of three
      classes of receptor antagonists including one with affinity of 0.5 microM, should
      provide important tools to assist in the identification of its natural ligand,
      the development of more potent selective receptor antagonists and agonists, and
      further exploration of the signaling properties of the hBRS-3 receptor.

PMID- 9593700
TI  - Interleukin (IL)-6 and its soluble receptor induce TIMP-1 expression in
      synoviocytes and chondrocytes, and block IL-1-induced collagenolytic activity.
AB  - To define the potential role of interleukin-6 (IL-6) and its soluble receptor
      alpha in cartilage metabolism, we analyzed their effects on tissue inhibitor of
      metalloproteases (TIMP) synthesis by synoviocytes and chondrocytes. TIMP-1
      production by isolated human articular synovial fibroblasts and chondrocytes,
      stimulated by IL-6 and/or its soluble receptor, was first assayed by specific
      enzyme-linked immunosorbent assay; the slight stimulatory effect of IL-6 on TIMP
      1 production by both types of cells was markedly amplified by the addition of
      soluble receptor, the maximal secretion being observed only at 96 h. TIMP-1 mRNA
      expression, determined by ribonuclease protection assay, was induced by IL-6
      together with its soluble receptor, but TIMP-2 and -3 mRNAs were not affected by
      these factors. A specific neutralizing antibody abolished the effects of the
      soluble receptor. Finally, supernatant from synoviocytes stimulated by IL-6 plus
      its soluble receptor blocked almost completely the collagenolytic activity of
      supernatant from IL-1-induced synoviocytes. These observations indicate that IL-6
      and its soluble receptor have a protective role in the metabolism of cartilage.
      Given the high levels of soluble receptor in synovial fluid and the marked
      induction of IL-6 by IL-1 or TNF-alpha, it is likely that IL-6 and its soluble
      receptor are critical in controlling the catabolic effects of pro-inflammatory
      cytokines.

PMID- 9593701
TI  - Human H-kininogen is a ferritin-binding protein.
AB  - H-kininogen is a multifunctional protein: it inhibits cysteine proteases, plays a
      role in contact activation of the coagulation cascade, and is the precursor of
      the potent proinflammatory peptide bradykinin. In the experiments described here,
      we identify H-kininogen as a ferritin-binding protein. Ferritin is a cellular and
      serum protein that is elevated in acute and chronic inflammation and many
      cancers. Despite numerous reports of ferritin-binding protein(s) in human serum,
      the nature and function of these proteins remain unclear. As a first step in
      characterizing the interaction between ferritin and its binding protein(s), we
      devised a ligand blot assay and used it to guide purification of a ferritin
      binding protein from human serum. Edman degradation of the purified protein
      determined the sequence HNLGHGHK(H)ERDQGHG, a sequence with identity to residues
      421-436 of human H-kininogen. These results were confirmed by demonstrating that
      commercially purified H-kininogen possessed ferritin binding activity and that
      ferritin binding could not be detected in plasma from kininogen-deficient
      individuals. Ligand blot assays mapped the ferritin binding domain to the light
      chain of H-kininogen chain, and revealed that both H and L recombinant ferritins
      possess H-kininogen binding activity. The unexpected identification of H
      kininogen as a ferritin-binding protein may link ferritin in the complex chain of
      interactions by which H-kininogen mediates its multiple effects in contact
      activation and inflammation.

PMID- 9593702
TI  - Activation of the human immunodeficiency virus long terminal repeat by varicella
      zoster virus IE4 protein requires nuclear factor-kappaB and involves both the
      amino-terminal and the carboxyl-terminal cysteine-rich region.
AB  - Varicella-zoster virus open reading frame 4-encoded protein (IE4) possesses
      transactivating properties for varicella-zoster virus genes as well as for those
      of heterologous viruses such as the human immunodeficiency virus type 1 (HIV-1).
      Mechanisms of HIV-1 LTR (long terminal repeat) transactivation were investigated
      in HeLa cells transiently transfected with an IE4 expression plasmid and a CAT
      reporter gene under the control of the HIV-1 LTR. These results demonstrated that
      IE4-mediated transactivation of the HIV-1 LTR in HeLa cells required
      transcription factor kappaB (NF-kappaB). Using the gel retardation assay, it was
      shown that transfection of the IE4 expression vector in HeLa cells was not
      associated with induction of NF-kappaB under the p50.p65 heterodimeric form and
      that no direct binding of IE4 to the kappaB sites could be detected. Both Western
      blot and immunofluorescence analyses suggested that the ability of IE4 to
      activate transcription through kappaB motives was not connected with its capacity
      to override the inhibitory activities of IkappaB-alpha or p105. Finally, in vitro
      protein-protein interactions involving IE4 and basal transcription factors such
      as TATA-binding protein and transcription factor IIB were carried out. A direct
      interaction between IE4 and TATA-binding protein or transcription factor IIB
      components of the basal complex of transcription was evidenced, as well as
      binding to the p50 and p65 NF-kappaB subunits. Mutagenesis analysis of IE4
      indicated that the COOH-terminal cysteine-rich and arginine-rich regions
      (residues 82-182) were critical for transactivation, whereas the first 81 amino
      acids appeared dispensable. Moreover, the arginine-rich region is required for
      the in vitro binding activity, whereas the COOH-terminal end did not appear
      essential.

PMID- 9593703
TI  - Hyperosmolality causes growth arrest of murine kidney cells. Induction of GADD45
      and GADD153 by osmosensing via stress-activated protein kinase 2.
AB  - Murine kidney cells of the inner medullary collecting duct (mIMCD) were exposed
      to either isosmotic (300 mosmol/kg) or hyperosmotic medium (isosmotic medium +
      150 mM NaCl) after seeding. We determined cell numbers, total nucleic acid, DNA,
      and RNA contents in both groups every day for a total period of 7 days. Based on
      all 4 parameters it was evident that growth of mIMCD3 cells is arrested for
      approximately 18 h following onset of hyperosmolality. However, none of the
      parameters measured indicated cell death because of hyperosmolality. Growth
      curves of hyperosmotic samples were shifted compared with isosmotic samples
      showing a gap of 18 h but had the same shape otherwise. We demonstrated that at
      24 and 48 h after onset of hyperosmolality, but not in isosmotic controls, growth
      arrest and DNA damage-inducible (GADD) proteins GADD45 and GADD153 are strongly
      induced. This result is consistent with growth arrest observed in hyperosmotic
      medium. We tested if mitogen- and stress-activated protein kinase (SAPK) cascades
      are involved in osmosignaling that leads to GADD45 and GADD153 induction. Using
      phosphospecific antibodies we showed that extracellular signal-regulated kinases
      1 and 2 (ERK), SAPK1 (JNK), and SAPK2 (p38) are hyperosmotically activated in
      mIMCD cells. Hyperosmotic GADD45 induction was significantly decreased by 37.5%
      following inhibition of the SAPK2 pathway, whereas it was significantly increased
      (65.2%) after inhibition of the ERK pathway. We observed similar, although less
      pronounced effects of SAPK2 and ERK inhibition on hyperosmotic GADD153 induction.
      In conclusion, we demonstrate that mIMCD cells arrest growth following
      hyperosmotic shock, that this causes strong induction of GADD45 and GADD153, that
      GADD induction is partially dependent on osmosignaling via SAPK2 and ERK, and
      that SAPK2 and ERK pathways have opposite effects on GADD expression.

PMID- 9593704
TI  - Carboxyl-terminal splicing of the rat mu opioid receptor modulates agonist
      mediated internalization and receptor resensitization.
AB  - The rat mu opioid receptor is alternatively spliced into two isoforms (MOR1 and
      MOR1B) which differ in length and amino acid composition at the carboxyl
      terminus. When stably expressed in HEK 293 cells, both splice variants bind the
      mu receptor agonist [D-Ala2,N-Me-Phe4,-Gly-ol5]enkephalin (DAMGO) with similar
      affinity and exhibit functional coupling to adenylyl cyclase with similar
      efficiency. However, the shorter isoform, MOR1B, desensitized at a slower rate
      during prolonged DAMGO exposure (4 h) but resensitized at a faster rate than MOR1
      during agonist withdrawal (20 min). Immunocytochemical analysis revealed that
      DAMGO-induced internalization of MOR1B proceeded much faster than that of MOR1
      followed by rapid recycling of the receptor to the cell surface. In addition, the
      greater resistance of MOR1B to homologous desensitization compared with MOR1 as
      well as MOR1B resensitization was abolished when receptor reactivation/recycling
      was blocked with monensin, an inhibitor of endosomal acidification. It is
      concluded that the sequence at the cytoplasmic tail of MOR1B facilitates clathrin
      coated vesicle-mediated endocytosis which, in turn, promotes accelerated receptor
      reactivation. Taken together, our findings suggest that carboxyl-terminal
      splicing of the rat mu opioid receptor modulates agonist-induced internalization
      and receptor resensitization.

PMID- 9593705
TI  - Identification of an FAD superfamily containing protoporphyrinogen oxidases,
      monoamine oxidases, and phytoene desaturase. Expression and characterization of
      phytoene desaturase of Myxococcus xanthus.
AB  - A large number of FAD-containing proteins have previously been shown to contain a
      signature sequence that is referred to as the dinucleotide binding motif.
      Protoporphyrinogen oxidase (PPO), the penultimate enzyme of the heme biosynthetic
      pathway, is an FAD-containing protein that catalyzes the six electron oxidation
      of protoporphyrinogen IX. Sequence analysis demonstrates the presence of the
      dinucleotide binding motif at the amino-terminal end of the protein. Analysis of
      the current data base reveals that PPO has significant sequence similarities to
      mammalian monoamine oxidases (MAO) A and B, as well as to bacterial and plant
      phytoene desaturases (PHD). Previously MAOs have been shown to contain FAD, but
      there are no publications demonstrating the presence of FAD in purified PHDs. We
      have carried out the expression and purification of PHD from the bacterium
      Myxococcus xanthus and demonstrate the presence of noncovalently bound FAD.
      Sequence analysis demonstrate that PPO is closely related to bacterial PHDs and
      more distantly to plant PHDs and animal MAOs. Interestingly bacterial MAOs are no
      more closely related to PPOs, PHDs, and animal MAO's than they are to the
      unrelated Pseudomonas phenyl hydroxylase. All of the related sequences contain
      not only the basic putative dinucleotide binding motif that is found frequently
      for FAD-binding proteins, but they also have high similarity in an approximately
      60-residue long region that extends beyond the dinucleotide motif. This region is
      not found among any other proteins in the current data base and, therefore, we
      propose that this region is a signature motif for a superfamily of FAD-containing
      enzymes that is comprised of PPOs, animal MAOs, and PHDs.

PMID- 9593706
TI  - Decrease in nucleoside diphosphate kinase (NDPK/nm23) expression during
      hematopoietic maturation.
AB  - The nucleoside diphosphate kinase (NDPK/nm23) isoforms H1 and H2 were localized
      in hematopoietic tissues. Flow cytometric analysis and enzymatic assays were used
      to quantify the intracellular and extracellular concentrations of NDPK. Bone
      marrow CD34(+) progenitors contained the highest intracellular levels of both
      nm23-H1 and nm23-H2. Lower levels were measured in more mature bone marrow cells,
      whereas peripheral blood leukocytes had the lowest expression of nm23. These data
      suggest a function of NDPK in early hematopoiesis and a down-regulation of NDPK
      upon differentiation. In addition, an up-regulation of nm23 expression was
      observed in lymphocytes after induction of proliferation with phytohemagglutinin.
      Multiparameter flow cytometry demonstrated that this up-regulation occurred
      during the G0/G1-transition. Flow cytometric analysis also revealed a weak
      surface expression of nm23 on a number of hematopoietic cell lines, which was not
      detected on normal hematopoietic cells. Our data also demonstrated the presence
      of NDPK in human plasma, probably due to a limited in vivo lysis of red blood
      cells.

PMID- 9593707
TI  - The Rho-deamidating cytotoxic necrotizing factor 1 from Escherichia coli
      possesses transglutaminase activity. Cysteine 866 and histidine 881 are essential
      for enzyme activity.
AB  - Recently, it has been reported that cytotoxic necrotizing factor 1 (CNF1) from
      Escherichia coli induces formation of stress fibers by deamidation of glutamine
      63 of RhoA (Schmidt, G., Sehr, P., Wilm, M., Selzer, J., Mann, M., and Aktories,
      K. (1997) Nature 387, 725-729); Flatau, G., Lemichez, E., Gauthier, M., Chardin,
      P., Paris, S., Fiorentini, C., and Boquet, P. (1997) Nature 387, 729-733). By
      using mass spectrometric analysis, we show now that the toxin transfers
      ethylenediamine, putrescine, and dansylcadaverine specifically onto glutamine 63
      of RhoA. RhoA was also a substrate for guinea pig liver transglutaminase, which
      modified not only glutamine 63, but also glutamine residues at positions 52 and
      136. Treatment of the fully active N-terminal fragment of CNF1 (amino acid
      residues 709-1014) with iodoacetamide inhibited both deamidation and
      transglutamination activities. Moreover, exchange of cysteine 866 with serine
      blocked the enzyme activity of the N-terminal CNF1 fragment. In addition, we
      identified histidine 881 to be essential for the enzyme activity of CNF1. The
      data indicate that CNF1 shares a catalytic dyad of cysteine and histidine
      residues with eukaryotic transglutaminases and cysteine proteases.

PMID- 9593708
TI  - Dynamics of protein kinase CK2 association with nucleosomes in relation to
      transcriptional activity.
AB  - Protein kinase CK2 has been implicated in control of cell growth and
      proliferation. Since growth stimuli evoke its preferential association with
      chromatin and nuclear matrix, we examined the dynamics of CK2 in nucleosomes
      fractionated on the basis of their transcriptional activity in the rat prostate.
      In this model, androgens induce expression of androgen-dependent genes but
      inhibit the androgen-repressed genes, whereas absence of androgens has the
      reverse effect. The level of CK2 was higher in the active than in inactive
      nucleosomes from normal prostate. Differential alterations in the levels of CK2
      activity in the transcriptionally active versus inactive nucleosomes were evoked
      by androgen deprivation or administration. Comparison of the distribution of CK2
      in active and inactive nucleosomes under varying androgenic conditions showed
      that the relative CK2 activity intrinsic to the transcriptionally active
      nucleosomes remained fairly stable, concordant with gene activity specific to the
      androgenic status. However, CK2 associated with inactive nucleosomes declined to
      a minimal level on androgen deprivation but increased rapidly on androgen
      administration (reflecting expression of multiple androgen-dependent genes). We
      suggest a role for CK2 in promoting the conformational transition of inactive
      nucleosomes to the active form and in the function of transcriptionally active
      nucleosomes.

PMID- 9593709
TI  - Identification of a candidate human spectrin Src homology 3 domain-binding
      protein suggests a general mechanism of association of tyrosine kinases with the
      spectrin-based membrane skeleton.
AB  - Spectrin is a widely expressed protein with specific isoforms found in erythroid
      and nonerythroid cells. Spectrin contains an Src homology 3 (SH3) domain of
      unknown function. A cDNA encoding a candidate spectrin SH3 domain-binding protein
      was identified by interaction screening of a human brain expression library using
      the human erythroid spectrin (alphaI) SH3 domain as a bait. Five isoforms of the
      alphaI SH3 domain-binding protein mRNA were identified in human brain. Mapping of
      SH3 binding regions revealed the presence of two alphaI SH3 domain binding
      regions and one Abl-SH3 domain binding region. The gene encoding the candidate
      spectrin SH3 domain-binding protein has been located to human chromosome 10p11.2 
      -> p12. The gene belongs to a recently identified family of tyrosine kinase
      binding proteins, and one of its isoforms is identical to e3B1, an eps8-binding
      protein (Biesova, Z., Piccoli, C., and Wong, W. T. (1997)Oncogene 14, 233-241).
      Overexpression of the green fluorescent protein fusion of the SH3 domain-binding
      protein in NIH3T3 cells resulted in cytoplasmic punctate fluorescence
      characteristic of the reticulovesicular system. This fluorescence pattern was
      similar to that obtained with the anti-human erythroid spectrin alphaI
      SigmaI/betaI SigmaI antibody in untransfected NIH3T3 cells; in addition, the anti
      alphaI SigmaI/betaI SigmaI antibody also stained Golgi apparatus.
      Immunofluorescence obtained using antibodies against alphaI SigmaI/++betaI SigmaI
      spectrin and Abl tyrosine kinase but not against alphaII/betaII spectrin
      colocalized with the overexpressed green fluorescent protein-SH3-binding protein.
      Based on the conservation of the spectrin SH3 binding site within members of this
      protein family and published interactions, a general mechanism of interactions of
      tyrosine kinases with the spectrin-based membrane skeleton is proposed.

PMID- 9593710
TI  - Transglutaminase 1 mutations in lamellar ichthyosis. Loss of activity due to
      failure of activation by proteolytic processing.
AB  - Lamellar ichthyosis is a congenital recessive skin disorder characterized by
      generalized scaling and hyperkeratosis. It is caused by mutations in the TGM1
      gene that encodes the transglutaminase 1 (TGase 1) enzyme, which is critical for
      the assembly of the cornified cell envelope in terminally differentiating
      keratinocytes. TGase 1 is a complex enzyme existing as both cytosolic and
      membrane-bound forms. Moreover, TGase 1 is proteolytically processed, and the
      major functionally active form consists of a membrane-bound 67/33/10-kDa complex
      with a myristoylated and palmitoylated amino-terminal 10-kDa membrane anchorage
      fragment. To understand better how point mutations, deletions, and truncations
      found in lamellar ichthyosis disease affect the structure and function of TGase
      1, we have expressed in baculovirus and keratinocytes a number of reported TGase
      1 mutants. The structural implications of these mutations were examined using a
      homology-derived three-dimensional model of TGase 1 generated from the known x
      ray structure of the related coagulation factor XIIIa enzyme. The present studies
      demonstrate that loss of TGase 1 activity is not restricted to mutations that
      directly affect the enzymatic activity. We report a new class of mutations that
      impair the subsequent post-synthetic processing of the protein into its highly
      active functional forms.

PMID- 9593711
TI  - Transient poly(ADP-ribosyl)ation of nuclear proteins and role of poly(ADP-ribose)
      polymerase in the early stages of apoptosis.
AB  - A transient burst of poly(ADP-ribosyl)ation of nuclear proteins occurs early,
      prior to commitment to death, in human osteosarcoma cells undergoing apoptosis,
      followed by caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP).
      The generality of this early burst of poly(ADP-ribosyl)ation has now been
      investigated with human HL-60 cells, mouse 3T3-L1, and immortalized fibroblasts
      derived from wild-type mice. The effects of eliminating this early transient
      modification of nuclear proteins by depletion of PARP protein either by antisense
      RNA expression or by gene disruption on various morphological and biochemical
      markers of apoptosis were then examined. Marked caspase-3-like PARP cleavage
      activity, proteolytic processing of CPP32 to its active form, internucleosomal
      DNA fragmentation, and nuclear morphological changes associated with apoptosis
      were induced in control 3T3-L1 cells treated for 24 h with anti-Fas and
      cycloheximide but not in PARP-depleted 3T3-L1 antisense cells exposed to these
      inducers. Similar results were obtained with control and PARP-depleted human
      Jurkat T cells. Whereas immortalized PARP +/+ fibroblasts showed the early burst
      of poly(ADP-ribosyl)ation and a rapid apoptotic response when exposed to anti-Fas
      and cycloheximide, PARP -/- fibroblasts exhibited neither the early poly (ADP
      ribosyl)ation nor any of the biochemical or morphological changes characteristic
      of apoptosis when similarly treated. Stable transfection of PARP -/- fibroblasts
      with wild-type PARP rendered the cells sensitive to Fas-mediated apoptosis. These
      results suggest that PARP and poly(ADP-ribosyl)ation may trigger key steps in the
      apoptotic program. Subsequent degradation of PARP by caspase-3-like proteases may
      prevent depletion of NAD and ATP or release certain nuclear proteins from
      poly(ADP-ribosyl)ation-induced inhibition, both of which might be required for
      late stages of apoptosis.

PMID- 9593712
TI  - GATA-6 induces p21(Cip1) expression and G1 cell cycle arrest.
AB  - GATA transcription factors represent a family of highly conserved zinc finger
      proteins with tissue-specific expression patterns. Previous studies have shown
      that GATA-6 is expressed in vascular smooth muscle cells (VSMCs) and rapidly down
      regulated when VSMCs are induced to proliferate. Here we investigated whether the
      GATA-6 transcription factor can modulate cellular proliferation. Transient
      transfection with a GATA-6 expression vector inhibited S-phase entry in VSMCs and
      in mouse embryonic fibroblasts (MEFs) lacking both p53 alleles. The GATA-6
      induced growth arrest correlated with a marked increase in the expression of the
      general cyclin-dependent kinase (Cdk) inhibitor p21. In contrast to p53-deficient
      MEFs and VSMCs, MEFs null for both p21 alleles were refractory to the GATA-6
      induced growth inhibition. These data demonstrate that elevated GATA-6 expression
      can promote the quiescent phenotype in VSMCs.

PMID- 9593713
TI  - Identification of the site of inhibition by omeprazole of a alpha-beta fusion
      protein of the H,K-ATPase using site-directed mutagenesis.
AB  - The alpha subunit of eukaryotic P-type ATPases has ten experimentally defined
      transmembrane or membrane inserted segments. The fifth and sixth of these are
      short, not predicted by hydropathy analysis, do not insert independently into
      microsomal membranes, and are readily removed after tryptic digestion and
      therefore may be membrane inserted sequences. Acid transport by the gastric H, K
      ATPase is covalently inhibited by several substituted pyridyl methylsulfinyl
      benzimidazoles, such as omeprazole. These act as probes of accessible
      extracytoplasmic thiols because they are accumulated in the acid transporting
      gastric vesicles and then convert to thiol reactive, cationic tetracyclic
      sulfenamides. Inhibition is due mainly to disulfide formation with Cys813 or
      Cys822 in M5/6 and perhaps with a contribution from Cys892 in the loop between
      transmembrane segment (TM) 7 and TM8. Identification of the specific cysteine
      responsible for inhibition should be able to define the turn between M5 and M6.
      The gastric H,K-ATPase alpha-beta heterodimer was expressed as a fusion protein
      in HEK 293 cells. Transient transfection resulted in most of the protein being
      retained in the endoplasmic reticulum with only core glycosylation and minor
      activity of the ATPase evident. Stable transfection resulted in plasma membrane
      localization of the protein and complex glycosylation. The transfected but not
      the control cells displayed cation-stimulated, SCH 28080-inhibited ATPase
      activity and SCH 28080- and omeprazole-inhibited 86Rb uptake. The two cysteines
      in M5/6 and Cys892 in the TM7/8 loop were mutated to the amino acids found in the
      Na,K-ATPase in order to determine which of the three cysteine residues were
      important for benzimidazole inhibition. Mutation of one, two, or all three
      cysteines did not alter enzyme activity, 86Rb transport, or SCH 28080 inhibition.
      Only removal of Cys822 blocked omeprazole inhibition of 86Rb transport. These
      data suggest that Cys822 is present in a region of the enzyme most easily
      accessed by the cationic sulfenamide formed by omeprazole, presumably the turn
      between M5 and M6.

PMID- 9593714
TI  - Cloning of human PEX cDNA. Expression, subcellular localization, and
      endopeptidase activity.
AB  - Mutations in the PEX gene are responsible for X-linked hypophosphatemic rickets.
      To gain insight into the role of PEX in normal physiology we have cloned the
      human full-length cDNA and studied its tissue expression, subcellular
      localization, and peptidase activity. We show that the cDNA encodes a 749-amino
      acid protein structurally related to a family of neutral endopeptidases that
      include neprilysin as prototype. By Northern blot analysis, the size of the full
      length PEX transcript is 6.5 kilobases. PEX expression, as determined by semi
      quantitative polymerase chain reaction, is high in bone and in tumor tissue
      associated with the paraneoplastic syndrome of renal phosphate wasting. PEX is
      glycosylated in the presence of canine microsomal membranes and partitions
      exclusively in the detergent phase from Triton X-114 extractions of transiently
      transfected COS cells. Immunofluorescence studies in A293 cells expressing PEX
      tagged with a c-myc epitope show a predominant cell-surface location for the
      protein with its COOH-terminal domain in the extracellular compartment,
      substantiating the assumption that PEX, like other members of the neutral
      endopeptidase family, is a type II integral membrane glycoprotein. Cell membranes
      from cultured COS cells transiently expressing PEX efficiently degrade
      exogenously added parathyroid hormone-derived peptides, demonstrating for the
      first time that recombinant PEX can function as an endopeptidase. PEX peptidase
      activity may provide a convenient target for pharmacological intervention in
      states of altered phosphate homeostasis and in metabolic bone diseases.

PMID- 9593715
TI  - Solution structure of leukemia inhibitory factor.
AB  - The solution structure of a murine-human chimera of leukemia inhibitory factor
      (LIF), a 180-residue cytokine with a molecular mass of 20 kDa, has been
      determined using multidimensional heteronuclear NMR techniques. The protein
      contains four alpha-helices, the relative orientations of which are well defined
      on the basis of long-range interhelical nuclear Overhauser effects. The helices
      are arranged in an up-up-down-down orientation, as found in other four-helix
      bundle cytokines, and the overall topology of the chimera is similar to that of
      the crystal structure of murine LIF (Robinson, R. C., Grey, L. M., Staunton, D.,
      Vankelecom, H. Vernallis, A. B., Moreau, J. F., Stuart, D. I., Heath, J. K., and
      Jones, E. Y. (1994) Cell 77, 1101-1116). Differences between the structures are
      evident in the N-terminal region, where the peptide bond preceding Pro17 has a
      trans-conformation in solution but a cis-conformation in the crystal, and in the
      small antiparallel beta-sheet encompassing residues in the N terminus and the CD
      loop in the crystal structure, which is not apparent in solution. There are also
      minor differences in the extent of the helices. Other than at the N terminus, the
      main difference between the two structures occurs at the C-terminal end of the CD
      loop. As this loop is close to a receptor-binding site on LIF that makes a major
      contribution to high affinity binding to the LIF receptor alpha-chain, these
      differences between the solution and crystal structures should be taken into
      account in structural models of LIF receptor interactions.

PMID- 9593716
TI  - Overexpression of a novel Xenopus rel mRNA gene induces tumors in early embryos.
AB  - The Rel family of transcriptional activators form a large diverse group of
      proteins that are involved in the activation of genes involved in immunity,
      development, apoptosis and cancer. So far, none of the rel genes cloned in
      mammals appear to be required for embryonic development. We have cloned and
      characterized a cDNA from an embryonic cDNA library that encodes a novel Xenopus
      Rel protein, called Xrel3. Xrel3 is a member of the cRel subfamily and is most
      closely related to but distinct from other Xenopus Rel members. The expression of
      Xrel3 mRNA was investigated using Northern analysis, RNase protection assay,
      reverse transcriptase-linked polymerase chain reaction and in situ hybridization.
      Messages are present maternally and are slightly enriched in the equatorial
      region of the blastula stage embryo. At gastrulation, the accumulation of Xrel3
      messages declines to undetectable levels but then increases after neurulation. In
      situ RNA hybridization was used to determine the spatial location of Xrel3
      messenger RNA in embryos. Messages are localized to the developing forebrain,
      dorsal mid-hindbrain region, the inner ear primordium, or otocyst, and in the
      notochord. Overexpression by microinjection of Xrel3 RNA induced tumors in the
      developing embryo that appeared after gastrulation. The location of the tumors
      depended on the location of the injection site. These results suggest that Xrel3
      might have a generalized role in regulation of cell differentiation in the
      embryo.

PMID- 9593717
TI  - Biochemical and structural analysis of the IgE binding sites on ara h1, an
      abundant and highly allergenic peanut protein.
AB  - Allergy to peanut is a significant IgE-mediated health problem because of the
      high prevalence, potential severity, and chronicity of the reaction. Ara h1, an
      abundant peanut protein, is recognized by serum IgE from >90% of peanut-sensitive
      individuals. It has been shown to belong to the vicilin family of seed storage
      proteins and to contain 23 linear IgE binding epitopes. In this communication, we
      have determined the critical amino acids within each of the IgE binding epitopes
      of Ara h1 that are important for immunoglobulin binding. Surprisingly,
      substitution of a single amino acid within each of the epitopes led to loss of
      IgE binding. In addition, hydrophobic residues appeared to be most critical for
      IgE binding. The position of each of the IgE binding epitopes on a homology-based
      molecular model of Ara h1 showed that they were clustered into two main regions,
      despite their more even distribution in the primary sequence. Finally, we have
      shown that Ara h1 forms a stable trimer by the use of a reproducible fluorescence
      assay. This information will be important in studies designed to reduce the risk
      of peanut-induced anaphylaxis by lowering the IgE binding capacity of the
      allergen.

PMID- 9593718
TI  - Cloning and characterization of a novel member of the transforming growth factor
      beta/bone morphogenetic protein family.
AB  - Members of the transforming growth factor-beta (TGF-beta) superfamily of growth
      and differentiation factors have been identified in a wide variety of organisms,
      ranging from invertebrates to mammals. Bone morphogenetic proteins (BMPs)
      constitute a subgroup of proteins belonging to the TGF-beta superfamily. BMPs
      were initially identified by their ability to induce endochondral bone formation
      at ectopic sites, suggesting a critical role for this family in development and
      regeneration of the skeleton. They are also expressed at a variety of nonskeletal
      sites during development, suggesting possible extraskeletal roles for these
      proteins. We cloned a novel member of the BMP family that is expressed at high
      levels in the placenta and the prostate and that we have designated as prostate
      derived factor (PDF). Based on cDNA sequence analysis, the predicted PDF protein
      contains two cysteines in addition to the seven conserved cysteines that are the
      hallmark of the members of the TGF-beta superfamily. In addition, Northern blot
      hybridization to poly(A)+ RNA showed low levels of expression in the kidney and
      pancreas. We further characterized the expression of this member of the BMP
      family by in situ hybridization and immunohistochemistry. These results show high
      expression in the terminal villae of the placenta. The expression of the protein
      as visualized by immunohistochemistry shows an expression pattern identical to
      that of the message in the terminal villae of the placenta. In day 18 rat
      embryos, protein expression was also seen in the skin and in the cartilaginous
      tissue of developing skeleton. Orchidectomy and dihydrotestosterone treatment of
      rats revealed that PDF expression is regulated by androgens in the prostate. In
      addition, subcutaneous implantation of recombinant PDF induced cartilage
      formation and the early stages of endochondral bone formation. These data
      indicate that PDF has a functional relationship to the BMPs.

PMID- 9593719
TI  - Specific regions of contact between human T-cell leukemia virus type I Tax
      protein and DNA identified by photocross-linking.
AB  - The human T-cell leukemia virus type I Tax protein forms a ternary complex on DNA
      in association with a host factor, the cyclic AMP response element-binding
      protein (CREB). An understanding of the precise geometry of this complex has been
      elusive. We have used photocross-linking to investigate Tax-DNA contacts. Our
      data show that Tax contacts the DNA at two symmetric positions 14 nucleotides
      apart on either side of the Tax responsive element. The presence of symmetric,
      widely separated regions of contact suggests that at least two molecules of Tax
      are present in the complex. Mapping the contacts onto a three-dimensional model
      of the CREB-DNA binary complex shows that they lie on the same face of the DNA
      near the regions where the N termini of the CREB bZIP domains enter the major
      groove. This location correlates well with previous evidence that CREB amino acid
      residues immediately N-terminal to the bZIP domain are crucial for the formation
      of the ternary complex. The limited number of cross-links observed suggests that
      contacts are primarily with the phosphate backbone and does not support the idea
      that a major structural element of the Tax protein inserts into the major or
      minor grooves of the DNA.

PMID- 9593721
TI  - Mapping of a minimal AU-rich sequence required for lipopolysaccharide-induced
      binding of a 55-kDa protein on tumor necrosis factor-alpha mRNA.
AB  - In monocyte/macrophage cells, the translation of tumor necrosis factor-alpha (TNF
      alpha) mRNA is tightly controlled. In unstimulated cells, TNF-alpha mRNA is
      translationally repressed. However, upon stimulation of the cells with various
      agents (e.g. lipopolysaccharides (LPS) and viruses), this repression is overcome
      and translation occurs. The key element in this regulation is the AU-rich
      sequence present in the 3'-untranslated region of TNF-alpha mRNA. Several groups
      have described the binding of proteins on AU-rich elements (AREs). We have
      previously reported the binding of two cytosolic protein complexes (1 and 2) to
      the TNF-alpha mRNA ARE, one of which (complex 2) is observed only following
      induction of TNF-alpha production by LPS. In this report, we have demonstrated
      that complex 1 involves a long fragment of the ARE, whereas the formation of the
      LPS-inducible complex 2 requires a minimal sequence which corresponds to the
      nonanucleotide UUAUUUAUU. Furthermore, we show that the RNA-binding protein
      involved in complex 2 has an apparent molecular mass of 55 kDa. Finally, we
      tested other AREs for their ability to form complex 2. We observed that the ARE
      derived from granulocyte/macrophage colony-stimulating factor mRNA, which does
      contain the nonanucleotide, is able to sustain the LPS-induced binding of the 55
      kDa protein. However, c-myc mRNA, which does not contain the nonanucleotide, is
      unable to promote the formation of any LPS-induced complex.

PMID- 9593720
TI  - Alterations in the GAL4 DNA-binding domain can affect transcriptional activation
      independent of DNA binding.
AB  - The GAL4 protein belongs to a large class of fungal transcriptional activator
      proteins encoding within their DNA-binding domains (DBD) six cysteines that
      coordinate two atoms of zinc (the Zn2Cys6 domain). In an effort to characterize
      the interactions between the Zn2Cys6 class transcriptional activator proteins and
      their DNA-binding sites, we have replaced in the full-length GAL4 protein small
      regions of the Zn2Cys6 domain with the analogous regions of another Zn2Cys6
      protein called PPR1 an activator of pyrimidine biosynthetic genes. Alterations
      between the first and third cysteines abolished binding to GAL4 (upstream
      activation sequence of GAL (UASG)) or PPR1 (upstream acitvation sequence of UAS)
      DNA-binding sites and severely reduced transcriptional activation in yeast. In
      contrast, alterations between the third and fourth cysteines had only minor
      effects on binding to UASG but led to substantial decreases in activation in both
      yeast and a mammalian cell line. In the crystal structure of the GAL4 DBD-UASG
      complex (Marmorstein, R., Carey, M., Ptashne, M., and Harrison, S. C. (1992)
      Nature 356, 408-414), this region is facing away from the DNA, making it likely
      that there exists within the GAL4 DBD an accessible domain important in
      activation.

PMID- 9593722
TI  - Molecular cloning of platelet factor XI, an alternative splicing product of the
      plasma factor XI gene.
AB  - Platelet factor XI is associated with the platelet plasma membrane and has an
      apparent Mr (220,000 nonreduced, 55,000 reduced) different from that of plasma
      factor XI. However, the site of synthesis and the nature of platelet factor XI
      are not known. Using reverse transcriptase polymerase chain reaction, 12 out of
      13 exons (all except exon V) coding for mature plasma factor XI were amplified
      from human platelet mRNA. The sequence of each of these exons was identical to
      that of plasma factor XI. In situ amplification and hybridization of factor XI
      mRNA was positive for exon III and negative for exon V in platelets and negative
      for both exons in other blood cells. By Northern hybridization, a factor XI mRNA
      transcript of approximately 1.9 kilobases was detected in megakaryocytic cells,
      and one of approximately 2.1 kilobases was detected in liver cells. Factor XI
      cDNA was cloned from a megakaryocyte library and sequenced. Exon V was absent,
      and the splicing of exon IV to exon VI maintained the open reading frame without
      alteration of the amino acid sequence except for the deletion of amino acids
      Ala91-Arg144 within the amino-terminal portion of the Apple 2 domain. Thus,
      platelet factor XI is an alternative splicing product of the factor XI gene,
      localized to platelets and megakaryocytes but absent from other blood cells.

PMID- 9593723
TI  - Bacterial expression and characterization of the mitochondrial outer membrane
      channel. Effects of n-terminal modifications.
AB  - Several forms of the voltage-dependent anion-selective channel (VDAC) have been
      expressed at high yield in Escherichia coli. Full-length constructs of the
      proteins of Neurospora crassa and Saccharomyces cerevisiae (ncVDAC and scVDAC)
      have been made with 20-residue-long, thrombin-cleavable, His6-containing N
      terminal extensions. ncVDAC purified from bacteria or mitochondria displays a far
      UV CD spectrum (in 1% lauryl dimethylamine oxide at pH 6-8) similar to that of
      bacterial porins, indicating extensive beta-sheet structure. Under the same
      conditions, the CD spectrum of bacterially expressed scVDAC indicates lower beta
      sheet content, albeit higher than that of mitochondrial scVDAC under the same
      conditions. In phospholipid bilayers, the bacterially expressed proteins (with or
      without N-terminal extensions) form typical VDAC-like channels with stable, large
      conductance open states (4-4.5 nanosiemens in 1 M KCl) and voltage-dependent
      transitions to a predominant substate (about 2 nanosiemens). A variant of scVDAC
      missing the first eight residues and having no N-terminal extension also has been
      expressed in E. coli. The truncated protein has a CD spectrum similar to that of
      mitochondrial scVDAC, but its channel activity is abnormal, exhibiting an
      unstable open state and rapid transitions between multiple subconductance levels.

PMID- 9593724
TI  - Herpes simplex virus type-1 single-strand DNA-binding protein (ICP8) enhances the
      ability of the viral DNA helicase-primase to unwind cisplatin-modified DNA.
AB  - The herpes simplex virus type-1 UL5, UL8, and UL52 genes encode an essential
      heterotrimeric DNA helicase-primase that is responsible for concomitant DNA
      unwinding and primer synthesis at the viral DNA replication fork. The viral
      single-strand DNA-binding protein (ICP8) can stimulate DNA unwinding by the
      helicase-primase as a result of a physical interaction that is mediated by the
      UL8 subunit. In this study, we investigated the ability of the helicase-primase
      to unwind a fork-like substrate that contains an intrastrand d(GpG) DNA cross
      link produced by the antitumor drug cisplatin. We also examined the ability of
      ICP8 to modulate the effect of the cisplatin lesion. The data show that the
      lesion inhibited the helicase-primase when located on the DNA strand along which
      it translocates. However, the lesion did not represent a permanent obstacle to
      its progression. In contrast, the adduct did not affect the helicase-primase when
      located on the opposite DNA strand. ICP8 specifically stimulated DNA unwinding by
      the helicase-primase. Coating concentrations of ICP8 were necessary for optimal
      unwinding of damaged DNA. Addition of competitor DNA to helicase reactions led to
      substantial reduction of DNA unwinding by the helicase-primase, suggesting that
      the enzyme is distributive. ICP8 did not abolish the competition, indicating that
      it did not stimulate the helicase by increasing its processivity. Rather, ICP8
      may stimulate DNA unwinding and enable bypass of cisplatin damaged DNA by
      recruiting the helicase-primase to the DNA.

PMID- 9593726
TI  - Alternative intracellular routing of ErbB receptors may determine signaling
      potency.
AB  - The ErbB signaling module consists of four receptor tyrosine kinases and several
      dozen ligands that activate specific homo- and heterodimeric complexes of ErbB
      proteins. Combinatorial ligand/receptor/effector interactions allow large
      potential for signal diversification. Here we addressed the possibility that turn
      off mechanisms enhance the diversification potential. Concentrating on ErbB-1 and
      two of its ligands, epidermal growth factor (EGF) and transforming growth factor
      alpha (TGF-alpha), and the Neu differentiation factor (NDF/neuregulin) and one of
      its receptors, ErbB-3, we show that ligand binding variably accelerates
      endocytosis of the respective ligand-receptor complex. However, unlike the EGF
      activated ErbB-1, which is destined primarily to degradation in lysosomes, NDF
      and TGF-alpha direct their receptors to recycling, probably because these ligands
      dissociate from their receptors earlier along the endocytic pathway. In the case
      of NDF, structural, as well as biochemical, analyses imply that ligand
      degradation occurs at a relatively late endosomal stage. Attenuation of receptor
      down-regulation by this mechanism apparently confers to both NDF and TGF-alpha
      more potent and prolonged signaling activity. In conclusion, alternative
      endocytic trafficking of ligand-ErbB complexes may tune and diversify signal
      transduction by EGF family ligands.

PMID- 9593725
TI  - Association of the insulin receptor with phospholipase C-gamma (PLCgamma) in 3T3
      L1 adipocytes suggests a role for PLCgamma in metabolic signaling by insulin.
AB  - Phospholipase C-gamma (PLCgamma) is the isozyme of PLC phosphorylated by multiple
      tyrosine kinases including epidermal growth factor, platelet-derived growth
      factor, nerve growth factor receptors, and nonreceptor tyrosine kinases. In this
      paper, we present evidence for the association of the insulin receptor (IR) with
      PLCgamma. Precipitation of the IR with glutathione S-transferase fusion proteins
      derived from PLCgamma and coimmunoprecipitation of the IR and PLCgamma were
      observed in 3T3-L1 adipocytes. To determine the functional significance of the
      interaction of PLCgamma and the IR, we used a specific inhibitor of PLC, U73122,
      or microinjection of SH2 domain glutathione S-transferase fusion proteins derived
      from PLCgamma to block insulin-stimulated GLUT4 translocation. We demonstrate
      inhibition of 2-deoxyglucose uptake in isolated primary rat adipocytes and 3T3-L1
      adipocytes pretreated with U73122. Antilipolytic effect of insulin in 3T3-L1
      adipocytes is unaffected by U73122. U73122 selectively inhibits mitogen-activated
      protein kinase, leaving the Akt and p70 S6 kinase pathways unperturbed. We
      conclude that PLCgamma is an active participant in metabolic and perhaps
      mitogenic signaling by the insulin receptor in 3T3-L1 adipocytes.

PMID- 9593727
TI  - Fibroblast transformation by Fps/Fes tyrosine kinases requires Ras, Rac, and
      Cdc42 and induces extracellular signal-regulated and c-Jun N-terminal kinase
      activation.
AB  - The small GTP-binding proteins Ras, Rac, and Cdc42 link protein-tyrosine kinases
      with mitogen-activated protein kinase (MAPK) signaling cascades. Ras controls the
      activation of extracellular signal-regulated kinases (ERKs), while Rac and Cdc42
      regulate the c-Jun N-terminal kinases (JNKs). In this study, we investigated
      whether small G protein/MAPK cascades contribute to signal transduction by
      transforming variants of c-Fes, a nonreceptor tyrosine kinase implicated in
      cytokine signaling and myeloid differentiation. First, we investigated the
      effects of dominant-negative small G proteins on Rat-2 fibroblast transformation
      by a retroviral homolog of c-Fes (v-Fps) and by c-Fes activated via N-terminal
      addition of the v-Src myristylation signal (Myr-Fes). We observed that dominant
      negative Ras, Rac, and Cdc42 inhibited v-Fps- and Myr-Fes-induced growth of Rat-2
      cells in soft agar, indicating that activation of these small GTP-binding
      proteins is required for fibroblast transformation by Fps/Fes tyrosine kinases.
      To determine whether MAPK pathways are activated downstream of these small G
      proteins, we measured ERK and JNK activity in the v-Fps- and Myr-Fes-transformed
      Rat-2 cells. Both ERK and JNK activities were elevated in the transformed cells,
      suggesting that these pathways are involved in cellular transformation. Dominant
      negative mutants of Ras (but not Rac or Cdc42) specifically inhibited ERK
      activation by v-Fps and Myr-Fes, demonstrating that ERK activation occurs
      exclusively downstream of Ras. All three dominant-negative small G proteins
      inhibited JNK activation by v-Fps and Myr-Fes, indicating that JNK activation by
      these tyrosine kinases requires both Ras and Rho family GTPases. These data
      demonstrate that multiple small G protein/MAPK cascades are involved in
      downstream signal transduction by Fps/Fes tyrosine kinases.

PMID- 9593728
TI  - The amino-terminal region of the luteinizing hormone/choriogonadotropin receptor
      contacts both subunits of human choriogonadotropin. I. Mutational analysis.
AB  - The luteinizing hormone/choriogonadotropin receptor is a seven-transmembrane
      receptor. Unlike most seven-transmembrane receptors, it is composed of two halves
      of equal size, the N-terminal extracellular exodomain and the C-terminal membrane
      associated endodomain. The exodomain is exclusively responsible for high affinity
      hormone binding, whereas receptor activation occurs only in the endodomain. This
      mutually exclusive physical separation of the two functional domains sets the
      lutropin receptor and its subfamily of receptors apart from all other seven
      transmembrane receptors. The mechanisms of hormone binding and receptor
      activation also appear to be different from those of other receptors in that
      binding occurs in at least two steps. However, the precise hormone contact sites
      in the exodomain are unknown. To determine the hormone/receptor contact sites, we
      have examined the receptor using progressive truncation from the C terminus, Ala
      scanning, immunofluorescence microscopy, and antibody binding. Progressive
      truncation from the C terminus of the receptor indicates several discrete regions
      that impact hormone binding. These regions are around the boundaries of exons 1
      2, 4-5, 6-7, and 9-10. Ala scanning of the Asp17-Arg26 region near the exon 1-2
      junction uncovered three alternating residues (Leu20, Cys22, and Gly24) crucial
      for hormone binding. Ala substitution for any one of these residues abolished
      hormone binding, although the resulting mutant receptors were successfully
      expressed on the cell surface. In contrast, Ala substitution for their flanking
      and intervening residues did not impair hormone binding. These results and the
      data in the accompanying article (Phang, T., Kundu, G., Hong, S., Ji, I., and Ji,
      T. (1998) J. Biol. Chem. 273, 13841-13847) indicate that this region directly
      contacts the hormone and suggest a novel mode of embracing the hormone.

PMID- 9593729
TI  - The amino-terminal region of the luteinizing hormone/choriogonadotropin receptor
      contacts both subunits of human choriogonadotropin. II. Photoaffinity labeling.
AB  - The luteinizing hormone/choriogonadotropin receptor, a seven-transmembrane
      receptor, is composed of two equal halves, the N-terminal extracellular exodomain
      and the C-terminal membrane-associated endodomain. Unlike most seven
      transmembrane receptors, the exodomain alone is responsible for high affinity
      hormone binding, whereas signal is generated in the endodomain. These physical
      separations of hormone-binding and receptor activation sites are attributed to
      unique mechanisms for hormone binding and receptor activation of this receptor
      and its subfamily members. However, the precise hormone contact sites in the
      exodomain are unclear. In the preceding article (Hong, S., Phang, T., Ji, I., and
      Ji, T. H. (1998) J. Biol. Chem. 273, 13835-13840), a region immediately
      downstream of the N terminus of the exodomain was shown to be crucial for hormone
      binding. To test if the region interacts with the hormone, human
      choriogonadotropin (hCG) was photoaffinity-labeled with a peptide mimic
      corresponding to Gly18-Tyr36 of the receptor. This peptide mimic specifically
      photoaffinity-labeled both the alpha- and beta-subunits of hCG. Interestingly,
      hCGalpha was preferentially labeled. On the other hand, denatured hCG was not
      labeled, and a mutant analog of the peptide failed to label hCG. Furthermore, the
      affinity labeling was UV-dependent and saturable, indicating the specificity of
      the photoaffinity labeling. Our results indicate that the region of the exodomain
      interacts with hCG and that the contact points are near both subunits of hCG.
      Particularly, the alternate residues (Leu20, Cys22, and Gly24) are crucial for
      hCG binding. In addition, the results underscore the fact that there is a crucial
      hormone contact site outside of the popularly believed primary hormone-binding
      site that is composed of Leu-rich repeats and is located in the middle of the
      exodomain. Our observations are crucial for understanding the molecular mechanism
      through which the initial high affinity hormone binding leads to receptor
      activation in the endodomain.

PMID- 9593730
TI  - Gene trapping identifies inhibitors of oncogenic transformation. The tissue
      inhibitor of metalloproteinases-3 (TIMP3) and collagen type I alpha2 (COL1A2) are
      epidermal growth factor-regulated growth repressors.
AB  - A gene trap strategy has been used to identify genes that are repressed in cells
      transformed by an activated epidermal growth factor (EGF)/EGF receptor signal
      transduction pathway. EGF receptor-expressing NIH3T3 cells (HER1 cells) were
      infected with a retrovirus containing coding sequences for the human CD2 antigen
      and for secreted alkaline phosphatase in the U3 region. By selecting for and
      against CD2 expression, we obtained clones in which the gene trap had integrated
      into genes selectively repressed by EGF. Two of these clones encoded for the
      secreted extracellular matrix proteins TIMP3 and COL1A2. We show here that both
      genes are downstream targets of RAS and are specifically repressed by EGF-induced
      transformation. Moreover, this strategy tags tumor suppressor genes in their
      normal chromosomal location, thereby improving target-specific screens for
      antineoplastic drugs.

PMID- 9593731
TI  - Identification of a cyclin subunit required for the function of Drosophila P
      TEFb.
AB  - P-TEFb is required for the transition from abortive elongation into productive
      elongation and is capable of phosphorylating the carboxyl-terminal domain (CTD)
      of the largest subunit of RNA polymerase II. We cloned a cDNA encoding the large
      subunit of Drosophila P-TEFb and found the predicted protein contained a cyclin
      motif. We now name the large subunit cyclin T and the previously cloned small
      subunit (Zhu, Y. R., Peery, T., Peng, J. M., Ramanathan, Y., Marshall, N.,
      Marshall, T., Amendt, B., Mathews, M. B., and Price, D. H. (1997) Genes Dev. 11,
      2622-2632) cyclin-dependent kinase 9 (CDK9). Recombinant P-TEFb produced in
      baculovirus-transfected Sf9 cells exhibited 5, 6-dichloro-1-beta-D
      ribofuranosylbenzimidazole-sensitive kinase activity similar to native P-TEFb. Kc
      cell nuclear extract depleted of P-TEFb failed to generate long DRB-sensitive
      transcripts, but this activity was restored upon addition of either native or
      recombinant P-TEFb. Like other CDKs, CDK9 is essentially inactive in the absence
      of its cyclin partner. P-TEFb containing a CDK9 mutation that knocked out the
      kinase activity did not function in transcription. Deletion of the carboxyl
      terminal domain of cyclin T in P-TEFb reduced both the kinase and transcription
      activity to about 10%. The CDK-activating kinase in TFIIH was unable to activate
      the CTD kinase activity of P-TEFb.

PMID- 9593732
TI  - Protein domains implicated in intracellular transport and sorting of lactase
      phlorizin hydrolase.
AB  - The roles of various domains of intestinal lactase-phlorizin hydrolase (pro-LPH)
      on its folding, dimerization, and polarized sorting are investigated in deletion
      mutants of the ectodomain fused or not fused with the membrane-anchoring and
      cytoplasmic domains (MACT). Deletion of 236 amino acids immediately upstream of
      MACT has no effect on the folding, dimerization, transport competence, or
      polarized sorting of the mutant LPH1646MACT. By contrast, LPH1646, an anchorless
      counterpart of LPH1646MACT, is not transported beyond the ER and persists as a
      mannose-rich monomer during its entire life cycle. The further deletion of 87
      amino acids generates a correctly folded but transport-incompetent monomeric
      LPH1559MACT mutant. The results strongly suggest that dimerization and transport
      of pro-LPH implicate a stretch of 87 amino acids in the ectodomain between
      LPH1646MACT and LPH1559MACT. In addition, dimerization of pro-LPH requires at
      least two further criteria: (i) a correctly folded ectodomain of pro-LPH and (ii)
      the presence of the transmembrane region. Neither of these requirements alone is
      sufficient for dimerization. Finally, the sorting of pro-LPH appears to be
      mediated by signals located between the cleavage site of pro-LPH and the
      LPH1646MACT mutant.

PMID- 9593733
TI  - Fas-induced arachidonic acid release is mediated by Ca2+-independent
      phospholipase A2 but not cytosolic phospholipase A2, which undergoes proteolytic
      inactivation.
AB  - Fas-mediated apoptosis of human leukemic U937 cells was accompanied by increased
      arachidonic acid (AA) and oleic acid release from membrane glycerophospholipids,
      indicating phospholipase A2 (PLA2) activation. During apoptosis, type IV
      cytosolic PLA2 (cPLA2), a PLA2 isozyme with an apparent molecular mass of 110 kDa
      critical for stimulus-coupled AA release, was converted to a 78-kDa fragment with
      concomitant loss of catalytic activity. Cleavage of cPLA2 correlated with
      increased caspase-3-like protease activity in apoptotic cells and was abrogated
      by a caspase-3 inhibitor. A mutant cPLA2 protein in which Asp522 was replaced by
      Asn, which aligns with the consensus sequence of the caspase-3 cleavage site
      (DXXD downward arrowX), was resistant to apo-ptosis-associated proteolysis.
      Moreover, a COOH-terminal deletion mutant of cPLA2 truncated at Asp522 comigrated
      with the 78-kDa fragment and exhibited no enzymatic activity. Thus, caspase-3
      mediated cPLA2 cleavage eventually leads to destruction of a catalytic triad
      essential for cPLA2 activity, thereby terminating its AA-releasing function. In
      contrast, the activity of type VI Ca2+-independent PLA2 (iPLA2), a PLA2 isozyme
      implicated in phospholipid remodeling, remained intact during apoptosis.
      Inhibitors of iPLA2, but neither cPLA2 nor secretory PLA2 inhibitors, suppressed
      AA release markedly and, importantly, delayed cell death induced by Fas.
      Therefore, we conclude that iPLA2-mediated fatty acid release is facilitated in
      Fas-stimulated cells and plays a modifying although not essential role in the
      apoptotic cell death process.

PMID- 9593734
TI  - Tyrosine phosphorylation of the beta3 cytoplasmic domain mediates integrin
      cytoskeletal interactions.
AB  - Tyrosine phosphorylation of the beta3 subunit of the major platelet integrin
      alphaIIb beta3 has been shown to occur during thrombin-induced platelet
      aggregation (1). We now show that a wide variety of platelet stimuli induced
      beta3 tyrosine phosphorylation, but that this phosphorylation occurred only
      following platelet aggregation. Several lines of evidence suggest that the beta3
      cytoplasmic domain tyrosine residues and/or their phosphorylation function to
      mediate interactions between beta3 integrins and cytoskeletal proteins. First,
      phospho-beta3 was retained preferentially in a Triton X-100 insoluble
      cytoskeletal fraction of thrombin-aggregated platelets. Second, in vitro
      experiments show that the cytoskeletal protein, myosin, associated in a
      phosphotyrosine-dependent manner with a diphosphorylated peptide corresponding to
      residues 740-762 of beta3. Third, mutation of both tyrosines in the beta3
      cytoplasmic domain to phenylalanines markedly reduced beta3-dependent fibrin clot
      retraction. Thus, our data indicate that platelet aggregation is both necessary
      and sufficient for beta3 tyrosine phosphorylation, and this phosphorylation
      results in the physical linkage of alphaIIb beta3 to the cytoskeleton. We
      hypothesize that this linkage may involve direct binding of the phosphorylated
      integrin to the contractile protein myosin in order to mediate transmission of
      force to the fibrin clot during the process of clot retraction.

PMID- 9593735
TI  - beta Recombinase catalyzes inversion and resolution between two inversely
      oriented six sites on a supercoiled DNA substrate and only inversion on relaxed
      or linear substrates.
AB  - The beta recombinase, in the presence of a chromatin-associated protein such as
      Hbsu, catalyzes DNA resolution or DNA inversion on supercoiled substrates
      containing two directly or inversely oriented six sites. Hbsu stabilizes the
      formation of the recombination complex (Alonso, J. C., Weise, F., and Rojo, F.
      (1995) J. Biol. Chem. 270, 2938-2945). In this study we show that resolution by
      beta recombinase strictly requires supercoiled DNA, but inversion does not. On a
      substrate with two inversely oriented six sites, beta recombinase catalyzed both
      resolution and inversion if the DNA was supercoiled but only inversion if the
      substrate was relaxed or linear. Hbsu was critical for the formation of synaptic
      complexes; its concentration relative to that of the supercoiled DNA substrate
      determined whether resolution or inversion products were preferentially formed.
      The results suggest that the beta recombinase forms unproductive short-lived
      synaptic complexes between two juxtaposed inversely oriented six sites; the
      presence of 3 to 13 Hbsu dimers per supercoiled DNA molecule would stabilize a
      synaptic complex with a relative geometry of the six sites allowing beta
      recombinase preferentially to achieve resolution. Supercoiling probably helps to
      overcome an energetic barrier, since resolution does not occur in relaxed DNA.
      The presence of >30 Hbsu dimers per DNA molecule probably favors the formation of
      a recombination complex with a different geometry since the reaction is directed
      preferentially toward DNA inversion.

PMID- 9593736
TI  - Physical interaction of ApoE with amyloid precursor protein independent of the
      amyloid Abeta region in vitro.
AB  - Variation at the APOE gene locus has been shown to affect the risk for
      Alzheimer's disease. To gain deeper insight into the postulated apoE-mediated
      amyloid formation, we have characterized the three common apoE isoforms (apoE2,
      apoE3, and apoE4) regarding their binding to amyloid precursor protein (APP). We
      employed the yeast two-hybrid system and co-immunoprecipitation experiments in
      cell culture supernatants of COS-1 cells, ectopically expressing apoE isoforms
      and APP751 holoprotein or a COOH-terminal Abeta deletion mutant protein,
      designated APPtrunc. We found that all three apoE isoforms were able to bind
      APP751 holoprotein in an Abeta-independent fashion. The interacting domains could
      be mapped to the NH2 termini of APP (amino acids 1-207) and apoE (amino acids 1
      191). As a functional consequence of this novel APP751 ectodomain-mediated apoE
      binding, the secretion of soluble APP751 is differentially affected by distinct
      apoE isoforms in vitro, suggesting a new "chaperon-like" mechanism by which apoE
      isoforms may modulate APP metabolism and consequently the risk for Alzheimer's
      disease.

PMID- 9593737
TI  - Requirements for the translocation of elongation-arrested, ribosome-associated
      OmpA across the plasma membrane of Escherichia coli.
AB  - An oligodeoxynucleotide-dependent method to generate nascent polypeptide chains
      was adopted for use in a cell-free translation system prepared from Escherichia
      coli. In this way, NH2-terminal pOmpA fragments of distinct sizes were
      synthesized. Because most of these pOmpA fragments could be covalently linked to
      puromycin, precipitated with cetyltrimethylammonium bromide, and were enriched by
      sedimentation, they represent a population of elongation-arrested, ribosome
      associated nascent chains. Translocation of these nascent pOmpA chains into
      inside-out membrane vesicles of E. coli required SecA and (depending on size)
      SecB. Whereas their translocation was strictly dependent on the H+-motive force
      of the vesicles, no indication for the involvement of the bacterial signal
      recognition particle was obtained. SecA and SecB, although required for
      translocation, did not mediate binding of the ribosome-associated pOmpA to
      membrane vesicles. However, SecA and SecB cotranslationally associated with
      nascent pOmpA, since they could be co-isolated with the ribosome-associated
      nascent chains and as such catalyzed translocation subsequent to the release of
      the ribosome. These results indicate that in E. coli, SecA also functionally
      interacts with preproteins before they are targeted to the translocase of the
      plasma membrane.

PMID- 9593738
TI  - Class A calcium channel variants in pancreatic islets and their role in insulin
      secretion.
AB  - The initiation of insulin release from rat islet beta cells relies, in large
      part, on calcium influx through dihydropyridine-sensitive (alpha1D) voltage-gated
      calcium channels. Components of calcium-dependent insulin secretion and whole
      cell calcium current, however, are resistant to L-type channel blockade, as well
      as to omega-conotoxin GVIA, a potent inhibitor of alpha1B channels, suggesting
      the expression of additional exocytotic calcium channels in the islet. We used a
      reverse transcription-polymerase chain reaction-based strategy to ascertain at
      the molecular level whether the alpha1A calcium channel isoform was also present.
      Results revealed two new variants of the rat brain alpha1A channel in the islet
      with divergence in a putative extracellular domain and in the carboxyl terminus.
      Using antibodies and cRNA probes specific for alpha1A channels, we found that the
      majority of cells in rat pancreatic islets were labeled, indicating expression of
      the alpha1A channels in beta cells, the predominant islet cell type.
      Electrophysiologic recording from isolated islet cells demonstrated that the
      dihydropyridine-resistant current was sensitive to the alpha1A channel blocker,
      omega-agatoxin IVA. This toxin also inhibited the dihydropyridine-resistant
      component of glucose-stimulated insulin secretion, suggesting functional overlap
      among calcium channel classes. These findings confirm the presence of multiple
      high voltage-activated calcium channels in the rat islet and implicate a
      physiologic role for alpha1A channels in excitation-secretion coupling in beta
      cells.

PMID- 9593739
TI  - ADAMTS-1 protein anchors at the extracellular matrix through the thrombospondin
      type I motifs and its spacing region.
AB  - Cellular disintegrin and metalloproteinases (ADAMs) are a family of genes with a
      sequence similar to those of snake venom metalloproteinases and disintegrins. The
      ADAMTS-1 gene encodes a new type of ADAM protein with respect to possessing the
      thrombospondin (TSP) type I motifs. Expression of the gene is induced in kidney
      and heart by in vivo administration of lipopolysaccharide, suggesting a possible
      role in the inflammatory reaction. In this study, we characterized the ADAMTS-1
      gene product by using a transient expression system in COS-7 cells. We found that
      the precursor and processed forms of ADAMTS-1 were secreted from cells. Under
      normal growth conditions, little or none of both forms was detected in the cell
      culture medium, and instead the majority was found associated with the
      extracellular matrix (ECM). In addition, when cells were cultured in the presence
      of heparin, the mature form of ADAMTS-1 protein was detected in the cell culture
      medium, suggesting that binding of ADAMTS-1 to the ECM is mediated through
      sulfated glycosaminoglycans such as heparan sulfate. Analyses of deletion mutants
      of the ADAMTS-1 protein revealed that the spacer region as well as three TSP type
      I motifs in the carboxyl-terminal region of the ADAMTS-1 protein are important
      for a tight interaction with the ECM. These results suggest that the ADAMTS-1 is
      a unique ADAM family protein that anchors at the ECM.

PMID- 9593740
TI  - Binding of hsp90 to the glucocorticoid receptor requires a specific 7-amino acid
      sequence at the amino terminus of the hormone-binding domain.
AB  - The glucocorticoid receptor (GR) HBD must be bound to the protein chaperone hsp90
      in order to acquire the high affinity steroid binding conformation. Despite this
      crucial role of hsp90, its binding site in GR remains poorly defined. Large
      portions of the GR HBD have been implicated and no similarity has been
      established between steroid receptor HBDs and the catalytic domains of the
      protein kinases (e.g. pp60(src), Raf) that also form stable heterocomplexes with
      hsp90. Thus, it has been thought that some general property of the proteins, such
      as exposure of hydrophobic residues in partially denatured regions, determines
      the assembly of stable hsp90 heterocomplexes. In this work, we have studied
      fusion proteins containing glutathione S-transferase (GST) and very short amino
      terminal truncations just before and at the beginning of the rat GR HBD that are
      otherwise intact to the carboxyl terminus. Overexpression in COS cells of the
      chimeras GST537C and GST547C was found to yield receptors that were bound to
      hsp90 and had wild-type steroid binding affinity. However, removal of 7 more
      amino acids to form GST554C resulted in a fusion protein that did not bind either
      hsp90 or steroid. Additional mutations revealed that the role of these 7 amino
      acids was neither to provide a spacer between protein domains nor to expose a
      protein surface by introducing a bend in the conserved alpha-helix. Instead,
      these observations support a model in which the sequence of the 7 amino acids
      directly or indirectly affects hsp90 binding to the GR HBD. Thus, a region of GR
      that has not been thought to be relevant for hsp90 binding is now seen to be of
      critical importance, and these data argue strongly against the commonly accepted
      model of receptor-hsp90 heterocomplex assembly in which the chaperone initially
      interacts nonspecifically with hydrophobic regions of the partially denatured HBD
      and subsequently assists its folding to the steroid binding confirmation.

PMID- 9593741
TI  - DNA topoisomerase I from Mycobacterium smegmatis. An enzyme with distinct
      features.
AB  - A type I topoisomerase has been purified to homogeneity from Mycobacterium
      smegmatis. It is the largest single subunit enzyme of this class having molecular
      mass of 110 kDa. The enzyme is Mg2+ dependent and can relax negatively
      supercoiled DNA, catenate, and knot single-stranded DNA, thus having typical
      properties of type I topoisomerases. Furthermore, the enzyme makes single
      stranded nicks and the 5'-phosphoryl end of the nicked DNA gets covalently linked
      with a tyrosine residue of the enzyme. However, M. smegmatis enzyme shows some
      distinctive features from the prototype Escherichia coli topoisomerase I. The
      enzyme is relatively stable at higher temperatures and not inhibited by
      spermidine. It apparently does not contain any bound Zn2+ and on modification of
      cysteine residues retains the activity, suggesting the absence of the zinc-finger
      motif in DNA binding. Partially purified Mycobacterium tuberculosis topoisomerase
      I exhibits very similar properties with respect to size, stability, and reaction
      characteristics. Sequence comparison of topoisomerase I from E. coli and M.
      tuberculosis shows the absence of zinc-finger motifs in mycobacterial enzyme.
      Using a two-substrate assay system, we demonstrate that the enzyme acts
      processively at low ionic strength and switches over to distributive mode at high
      Mg2+ concentration. Significantly, the enzyme activity is stimulated by single
      strand DNA-binding protein. There is a potential to exploit the characteristics
      of the enzyme to develop it as a molecular target against mycobacterial
      infections.

PMID- 9593742
TI  - Glycosylation profile of a recombinant urokinase-type plasminogen activator
      receptor expressed in Chinese hamster ovary cells.
AB  - Association of urokinase-type plasminogen activator (uPA) to cells via binding to
      its specific cellular receptor (uPAR) augments the potential of these cells to
      support plasminogen activation, a process that has been implicated in the
      degradation of extracellular matrix proteins during cell migration and tissue
      remodeling. The uPA receptor is a glycolipid-anchored membrane protein belonging
      to the Ly-6/uPAR superfamily and is the only multidomain member identified so
      far. We have now purified the three individual domains of a recombinant soluble
      uPAR variant, expressed in Chinese hamster ovary cells, after limited proteolysis
      using chymotrypsin and pepsin. The glycosylation patterns of these domains have
      been determined by matrix assisted laser desorption ionization and electrospray
      ionization mass spectrometry. Of the five potential attachment sites for
      asparagine-linked carbohydrate in uPAR only four are utilized, as the tryptic
      peptide derived from domain III containing Asn233 was quantitatively recovered
      without carbohydrate. The remaining four attachment sites were shown to exhibit
      site-specific microheterogeneity of the asparagine-linked carbohydrate. The
      glycosylation on Asn52 (domain I) and Asn172 (domain II) is dominated by the
      smaller biantennary complex-type oligosaccharides, while Asn162 (domain II) and
      Asn200 (domain III) predominantly carry tri- and tetraantennary complex-type
      oligosaccharides. The carbohydrate moiety on Asn52 in uPAR domain I could be
      selectively removed by N-glycanase treatment under nondenaturing conditions. This
      susceptibility was abrogated when uPAR participitated in a bimolecular complex
      with pro-uPA or smaller receptor binding derivatives thereof, demonstrating the
      proximity of the ligand-binding site to this particular carbohydrate moiety. uPAR
      preparations devoid of carbohydrate on domain I exhibited altered binding
      kinetics toward uPA (a 4-6-fold increase in Kd) as assessed by real time
      biomolecular interaction analysis.

PMID- 9593743
TI  - Modulation of interferon-gamma-induced macrophage activation by phosphotyrosine
      phosphatases inhibition. Effect on murine Leishmaniasis progression.
AB  - Phagocyte functions are markedly inhibited after infection with the intracellular
      protozoan parasite Leishmania. This situation strongly favors the installation
      and propagation of this pathogen within its mammalian host. Previous findings by
      us and others have established that alteration of several signaling pathways
      (protein kinase C-, Ca2+- and protein-tyrosine kinases-dependent signaling
      events) were directly responsible for Leishmania-induced macrophage (MO)
      dysfunctions. Here we report that modulation of phosphotyrosine-dependent events
      with a protein tyrosine phosphatases (PTP) inhibitor, the peroxovanadium (pV)
      compound bpV(phen) (potassium bisperoxo(1,10-phenanthroline)oxovanadate(Vi)), can
      control host-pathogen interactions by different mechanisms. We observed that the
      inhibition of parasite PTP resulted in an arrest of proliferation and death of
      the latter in coincidence with cyclin-dependent kinase (CDK1) tyrosine 15
      phosphorylation. Moreover the treatment of MO with bpV(phen) resulted in an
      increased sensitivity to interferon-gamma stimulation, which was reflected by
      enhanced nitric oxide (NO) production. This enhanced IFN-gamma-induced NO
      generation was accompanied by a marked increase of inducible nitric oxide
      synthase (iNOS) mRNA gene and protein expression. Finally we have verified the in
      vivo potency of bpV(phen) over a 6-week period of daily administration of a sub
      toxic dose. The results revealed its effectiveness in controlling the progression
      of visceral and cutaneous leishmaniasis. Therefore PTP inhibition of Leishmania
      and MO by the pV compound bpV(phen) can differentially affect these eukaryotic
      cells. This strongly suggests that PTP plays an important role in the progression
      of Leishmania infection and pathogenesis. The apparent potency of pV compounds
      along with their relatively simple and versatile structure render them attractive
      pharmacological agents for the management of parasitic infections.

PMID- 9593744
TI  - Association of XK and Kell blood group proteins.
AB  - A disulfide bond links Kell and XK red cell membrane proteins. Kell, a type II
      membrane glycoprotein, carries over 20 blood group antigens, and XK, which spans
      the membrane 10 times, is lacking in rare individuals with the McLeod syndrome.
      Kell is classified in the neprilysin family of zinc endopeptidases, and XK has
      structural features that suggest it is a transport protein. Kell has 15
      extracellular cysteines, and XK has one in its fifth extracellular loop. Five of
      the extracellular cysteine residues in Kell are not conserved in the other
      members of the neprilysin family, and based on the hypothesis that one of the
      nonconserved cysteines is linked to XK, cysteines 72 and 319 were mutated to
      serine. The single extracellular cysteine 347 of XK was also mutated. Co
      expression of combinations of wild-type and mutant proteins in transfected COS-1
      cells showed that Kell C72S did not form a Kell-XK complex with wild-type XK,
      while wild-type Kell and Kell C319S did. XK C347S was also unable to form a
      complex with wild-type Kell, indicating that Kell cysteine 72 is linked to XK
      cysteine 347. Kell C72S was transported to the cell surface, indicating that
      linkage to XK is not required. In addition, chemical cross-linking of red cell
      membranes with dithiobispropionimidate indicated that glyceraldehyde-3-phosphate
      dehydrogenase is a near neighbor of Kell.

PMID- 9593745
TI  - PU.1, interferon regulatory factor 1, and interferon consensus sequence-binding
      protein cooperate to increase gp91(phox) expression.
AB  - gp91(phox) is a subunit of the phagocyte respiratory burst oxidase catalytic
      unit. Transcription of CYBB, the gene encoding gp91(phox), is restricted to
      terminally differentiated phagocytic cells. An element in the proximal CYBB
      promoter binds a protein complex, referred to as hematopoiesis-associated factor
      (HAF1), that is necessary for interferon-gamma (IFNgamma)-induced gp91(phox)
      expression. In these investigations, we determined that HAF1 was a multiprotein
      complex, cross-immunoreactive with the transcription factors PU.1, interferon
      regulatory factor 1 (IRF-1), and interferon consensus sequence-binding protein
      (ICSBP). In electrophoretic mobility shift assay, the HAF1 complex was
      reconstituted by either in vitro translated PU.1 with IRF-1 or PU.1 with ICSBP,
      but not by IRF-1 with ICSBP. HAF1a, a slower mobility complex with the same
      binding site specificity as HAF1, was also investigated. Similar to the HAF1
      complex, the HAF1a complex was cross-immunoreactive with PU. 1, IRF-1, and ICSBP.
      Unlike the HAF1 complex, reconstitution of the HAF1a complex required in vitro
      translated PU.1 with both IRF-1 and ICSBP. An artificial promoter construct
      containing the HAF1/HAF1a binding site was modestly activated in the
      myelomonocytic cell line U937 by co-transfection either with PU.1 and IRF-1 or
      with PU.1 and ICSBP, but it was strongly activated by co-transfection with PU.1,
      IRF-1, and ICSBP. This activation required serine 148-phosphorylated PU.1. These
      studies describe a novel mechanism for PU.1 transcriptional activation via
      interaction with both IRF-1 and ICSBP, a target gene for the interaction of IRF-1
      with ICSBP, and a novel activation function for ICSBP as a component of a
      multiprotein complex.

PMID- 9593746
TI  - Astrocyte progression from G1 to S phase of the cell cycle depends upon multiple
      protein interaction.
AB  - The proliferation of cultured astrocytes is positively and negatively regulated,
      respectively, by the endogenous neuropeptides, endothelin-3 (ET-3) and atrial
      natriuretic peptide (ANP). Here, we determined the important steps for the
      modulation by ET and ANP of G1 to S phase cell cycle progression. ET-3 stimulated
      an increased number of fetal rat diencephalic astrocytes to progress through
      G1/S, and this was blocked significantly by ANP. ET augmented the gene expression
      and/or protein production of D-type, A and E cyclins, whereas ANP inhibited these
      events significantly. ET also stimulated the activation of the cyclin-dependent
      kinases Cdk2, Cdk4, and Cdk6, directed against the retinoblastoma protein pRb,
      and this was inhibited by as much as 80% by ANP. As an additional mechanism of
      cell cycle restraint, ANP stimulated the production of multiple cyclin-dependent
      kinase inhibitory (CKI) proteins, including p16, p27, and p57. This was critical
      because antisense oligonucleotides to each CKI reversed ANP-induced inhibition of
      ET-stimulated DNA synthesis by as much as 85%. CKI antisense oligonucleotides
      also reversed the ANP inhibition of Cdk phosphorylation of pRb. In turn, ET
      inhibited ANP-stimulated production of the CKIs, thereby promoting cell cycle
      progression. Specific and changing associations of the CKI with Cdk2 and Cdk4
      were stimulated by ANP and inhibited by ET. Our findings identify several
      mechanisms by which endogenous modulators of astrocyte proliferation can control
      the G1-S progression and indicate that multiple CKIs are necessary to restrain
      cell cycle progression in these cells.

PMID- 9593747
TI  - Characterization of the microtubule-binding domain of microtubule-associated
      protein 1A and its effects on microtubule dynamics.
AB  - To determine how MAP1a interacts with microtubules we expressed several 6myc
      tagged MAP1a fragments in P19 EC and HeLa cells. Confocal immunofluorescence
      microscopy showed that the fragment consisting of amino acids (aa) 1-281 of MAP1a
      did not bind while the fragment consisting of aa 1-630 did, indicating that the
      region of MAP1a between aa 281 and 630 contains a microtubule-binding domain.
      Deletion of the basic repeats from aa 336-540 did not result in loss of
      microtubule binding, suggesting that the regions flanking the basic repeats can
      bind MAP1a to microtubules. These observations were confirmed using an in vitro
      microtubule binding assay. The levels of acetylation and detyrosination of
      polymerized microtubules were assessed by quantitative dot blotting in cells
      expressing MAP1a fragments or MAP2c. Compared with untransfected cells, the
      polymerized tubulin in cells expressing full-length MAP1a was more acetylated and
      detyrosinated, but these increases were smaller than those seen in cells
      expressing MAP2c. Consistent with this, the microtubules in MAP2c expressing
      cells were more resistant to colchicine than those in cells overexpressing MAP1a.
      These data implicate aa 281-336 and/or 540-630 of MAP1a in microtubule binding
      and suggest that MAP1a is less able to stabilize microtubules than MAP2c.

PMID- 9593748
TI  - Structure of the human sarco/endoplasmic reticulum Ca2+-ATPase 3 gene. Promoter
      analysis and alternative splicing of the SERCA3 pre-mRNA.
AB  - Human chromosome 17-specific genomic clones extending over 90 kilobases (kb) of
      DNA and coding for sarco/endoplasmic reticulum Ca2+-ATPase 3 (SERCA3) were
      isolated. The presence of the D17S1828 genetic marker in the cosmid contig
      enabled us to map the SERCA3 gene (ATP2A3) 11 centimorgans from the top of the
      short arm p of chromosome 17, in the vicinity of the cystinosis gene locus. The
      SERCA3 gene contains 22 exons spread over 50 kb of genomic DNA. The exon/intron
      boundaries are well conserved between human SERCA3 and SERCA1 genes, except for
      the junction between exons 8 and 9 which is found in the SERCA1 gene but not in
      SERCA3 and SERCA2 genes. The transcription start site (+1) is located 152
      nucleotides (nt) upstream of the AUG codon. The 5'-flanking region, including
      exon 1, is embedded in a 1.5-kb CpG island and is characterized by the absence of
      a TATA box and by the presence of 14 putative Sp1 sites, 11 CACCC boxes, 5 AP-2
      binding motifs, 3 GGCTGGGG motifs, 3 CANNTG boxes, a GATA motif, as well as
      single sites for Ets-1, c-Myc, and TFIIIc. Functional promoter analysis indicated
      that the GC-rich region (87% G + C) from -135 to -31 is of critical importance in
      initiating SERCA3 gene transcription in Jurkat cells. Exon 21 (human, 101 base
      pairs; mouse, 86 base pairs) can be alternatively excluded, partially included,
      or totally included, thus generating, respectively, SERCA3a (human and mouse, 999
      amino acids (aa)), SERCA3b (human, 1043 aa; mouse, 1038 aa), or SERCA3c (human,
      1024 aa; mouse, 1021 aa) isoforms with different C termini. Expression of the
      mouse SERCA3 isoforms in COS-1 cells demonstrated their ability to function as
      active pumps, although with different apparent affinities for Ca2+.

PMID- 9593749
TI  - Direct interaction of a Ca2+-binding loop of synaptotagmin with lipid bilayers.
AB  - Synaptotagmin 1 binds Ca2+ and membranes via its C2A-domain and plays an
      essential role in excitation-secretion coupling. In this study, we sought to
      identify Ca2+- and membrane-induced local conformational changes in the C2A
      domain of synaptotagmin and to delineate the C2A-lipid binding interface. To
      address these questions native phenylalanine residues were replaced, at each face
      of the domain, with tryptophan reporters. Changes in tryptophanyl fluorescence
      indicated that Ca2+ induced long range conformational changes throughout C2A,
      including regions distant from an established Ca2+-binding site. Addition of
      liposomes resulted in Ca2+-dependent increases in the fluorescence of tryptophans
      193, 231, and 234. Only the tryptophan residues at positions 234 and 231, which
      lie within a Ca2+-binding loop of C2A, exhibited liposome-induced blue shifts in
      their emission spectra. Quenching experiments, using membrane-imbedded doxyl spin
      labels, revealed that tryptophan residues 231 and 234 penetrated lipid bilayers.
      These data delineate the lipid binding interface of C2A and provide the first
      evidence for adjacent Ca2+- and lipid-binding sites within a C2-domain. The
      penetration of C2A into membranes may function to bring components of the fusion
      machinery into contact with the lipid bilayer to initiate exocytosis.

PMID- 9593750
TI  - 4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein
      family.
AB  - Translation initiation in eukaryotes is mediated by the cap structure (m7GpppN,
      where N is any nucleotide) present at the 5' end of all cellular mRNAs, except
      organellar. The cap is recognized by eukaryotic initiation factor 4F (eIF4F),
      which consists of three polypeptides, including eIF4E, the cap-binding protein
      subunit. The interaction of the cap with eIF4E facilitates the binding of the
      ribosome to the mRNA. eIF4E activity is regulated in part by two translational
      repressors, 4E-BP1 and 4E-BP2, which bind to it and prevent its assembly into
      eIF4F. We report here the isolation of 4E-BP3, a new member of the 4E-BP family.
      4E-BP3 is homologous to 4E-BP1 and 4E-BP2, exhibiting 57 and 59% identity,
      respectively. The homology is most striking in the middle region of the protein,
      which contains the eIF4E binding motif and residues that are phosphorylated in 4E
      BP1. 4E-BP3 is a heat stable protein that binds to eIF4E in vitro as well as in
      vivo. Further, 4E-BP3 overexpression specifically reduces eIF4E-dependent
      translation. The overlapping function and expression of the different 4E-BP
      family members imply that there is redundancy in this translational control
      mechanism, underscoring its importance.

PMID- 9593751
TI  - Constitutive activation of NF-kappaB causes resistance to apoptosis in human
      cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor
      and reactive oxygen intermediates.
AB  - How tumor cells develop resistance to apoptosis induced by cytokines and
      chemotherapeutic agents is incompletely understood. In the present report, we
      investigated apoptosis induction by tumor necrosis factor (TNF) in two human T
      cell lines, Jurkat and HuT-78. While TNF inhibited the growth of Jurkat cells and
      activated caspase-3, it had no effect on HuT-78 cells. It was further found that
      HuT-78 cells constitutively expressed the nuclear transcription factor NF-kappaB.
      TNF activated NF-kappaB in Jurkat cells but not in HuT-78 cells. HuT-78 cells
      were also resistant to NF-kappaB activation induced by phorbol ester, H2O2,
      ceramide, endotoxin, and interleukin-1. Despite the presence of preactivated NF
      kappaB, HuT-78 cells also expressed high levels of IkappaB-alpha, the inhibitory
      subunit of NF-kappaB and, unlike Jurkat cells, were resistant to TNF-induced
      degradation of IkappaB-alpha. Its half-life in HuT-78 cells was 12 h as opposed
      to 45 min in Jurkat cells. Antibodies against TNF blocked the constitutive
      activation of NF-kappaB and proliferation of HuT-78 cells but had no significant
      effect on Jurkat cells, suggesting an autocrine role for TNF. The antioxidant
      pyrrolidine dithiocarbamate also suppressed constitutive NF-kappaB activation and
      it reversed the cell's sensitivity to TNF-induced cytotoxicity and activation of
      caspase-3. Overall, these results suggest that constitutive activation of NF
      kappaB, TNF, and prooxidant pathway in certain T cell lymphomas causes resistance
      to apoptosis, and this can be reversed by antioxidants.

PMID- 9593752
TI  - Regulation of amyloid precursor protein secretion by glutamate receptors in human
      Ntera 2 neurons.
AB  - The amyloid precursor protein (APP) can be cleaved by a beta-secretase to
      generate a beta-amyloid peptide, which has been implicated in the pathogenesis of
      Alzheimer's disease. However, APP can also be cleaved by an alpha-secretase to
      form a non-amyloidogenic secreted form of APP (APP-S). APP-S secretion can be
      physiologically regulated. This study examined the glutamatergic regulation of
      APP in the human neuronal Ntera 2 (NT2N) cell line. Metabotropic glutamate
      receptor subtypes 1alpha/beta and 5alpha were identified in the NT2N neurons by
      reverse transcription-polymerase chain reaction. Stimulation of these
      phosphatidylinositol-linked receptors with glutamate or specific receptor
      agonists resulted in a dose- and time-dependent increase in the secretion of the
      amyloid precursor protein (APP-S), measured by the immunoprecipitation of APP-S
      from the medium of [35S]methionine-labeled NT2N neurons. The glutamate-induced
      APP-S secretion was maximal at 30 min and at a concentration of 1 mM glutamate.
      Glutamate-induced APP-S secretion required activation of phospholipase C, which
      resulted in inositol 1, 4,5-trisphosphate production, as shown by the rapid
      glutamate-induced accumulation of inositol 1,4,5-trisphosphate. Glutamate also
      caused an increase in intracellular Ca2+. The protein kinase C activator phorbol
      12-myristate 13-acetate, a phorbol ester, as well as 1-oleoyl-2-acetoyl-3
      glycerol, a cell-permeable diacylglycerol analog, also stimulated APP-S
      secretion. These findings suggest that APP-S secretion from NT2N neurons can be
      regulated by the activation of phosphatidylinositol-linked metabotropic glutamate
      receptor signaling pathway.

PMID- 9593753
TI  - Cloning and characterization of a second human CTP:phosphocholine
      cytidylyltransferase.
AB  - CTP:phosphocholine cytidylyltransferase (CCT) is a key regulator of
      phosphatidylcholine biosynthesis, and only a single isoform of this enzyme,
      CCTalpha, is known. We identified and sequenced a human cDNA that encoded a
      distinct CCT isoform, called CCTbeta, that is derived from a gene different from
      that encoding CCTalpha. CCTbeta transcripts were detected in human adult and
      fetal tissues, and very high transcript levels were found in placenta and testis.
      CCTbeta and CCTalpha proteins share highly related, but not identical, catalytic
      domains followed by three amphipathic helical repeats. Like CCTalpha, CCTbeta
      required the presence of lipid regulators for maximum catalytic activity. The
      amino terminus of CCTbeta bears no resemblance to the amino terminus of CCTalpha,
      and CCTbeta protein was localized to the cytoplasm as detected by indirect
      immunofluorescent microscopy. Whereas CCTalpha activity is regulated by
      reversible phosphorylation, CCTbeta lacks most of the corresponding carboxyl
      terminal domain and contained only 3 potential phosphorylation sites of the 16
      identified in CCTalpha. Transfection of COS-7 cells with a CCTbeta expression
      construct led to the overexpression of CCT activity, the accumulation of cellular
      CDP-choline, and enhanced radiolabeling of phosphatidylcholine. CCTbeta protein
      was posttranslationally modified in COS-7 cells, resulting in slower migration
      during polyacrylamide gel electrophoresis. Expression of CCTbeta/CCTalpha
      chimeric proteins showed that the amino-terminal portion of CCTbeta was required
      for posttranslational modification. These data demonstrate that a second,
      distinct CCT enzyme is expressed in human tissues and provides another mechanism
      by which cells regulate phosphatidylcholine production.

PMID- 9593754
TI  - Expression of the Cdx1 and Cdx2 homeotic genes leads to reduced malignancy in
      colon cancer-derived cells.
AB  - We have previously described an inverse relationship between Cdx1 and Cdx2 mRNA
      levels and the extent of dysplasia and severity of clinical outcome in colorectal
      carcinoma, suggesting that altered expression of these genes was associated with
      colorectal carcinogenesis or tumor progression. To investigate further their
      involvement in the physiopathology of colorectal cancer, HT29 colon carcinoma
      cells that show very low Cdx expression were transfected with Cdx1 and/or Cdx2
      cDNA to elicit their overexpression. Growth rate, tumorigenicity, resistance to
      apoptosis, and migration potential of the corresponding cells were analyzed.
      Growth rate of cells overexpressing Cdx2 decreased by half, whereas
      overexpression of Cdx1 had no effect. However, cells overexpressing both Cdxs had
      a growth rate reduced to 20% of control. In cells overexpressing Cdx1 or Cdx2,
      tumorigenicity and resistance to apoptosis induced by serum starvation, ceramide,
      or staurosporine were not changed compared with control cells; yet phorbol ester
      stimulated cell migration was decreased by 50%. In cells overexpressing both Cdx1
      and Cdx2, tumorigenicity was decreased by 50%, resistance to apoptosis was
      significantly lowered, and stimulated cell migration was further decreased to 15%
      of control compared with cells expressing Cdx1 or Cdx2. Finally, cells
      overexpressing both Cdxs showed strongly decreased Bcl-2 expression, which could
      account for their increased sensitivity to apoptosis. These findings show that,
      in HT29 cells, both Cdx1 and Cdx2 genes must be expressed to reduce tumorigenic
      potential, to increase sensitivity to apoptosis, and to reduce cell migration,
      suggesting that the two genes control the normal phenotype by independent
      pathways. This may explain why loss of Cdx1 or Cdx2 expression is associated with
      tumor development and invasiveness in colorectal tumors.

PMID- 9593755
TI  - Identification of a palmitic acid-modified form of human Sonic hedgehog.
AB  - During hedgehog biosynthesis, autocatalytic processing produces a lipid-modified
      amino-terminal fragment (residues 24-197 in the human Sonic hedgehog sequence)
      that is responsible for all known hedgehog signaling activity and that is highly
      conserved evolutionarily. Published in vitro biochemical studies using Drosophila
      hedgehog identified the membrane anchor as a cholesterol, and localized the site
      of attachment to the COOH terminus of the fragment. We have expressed full-length
      human Sonic hedgehog in insect and in mammalian cells and determined by mass
      spectrometry that, in addition to cholesterol, the human hedgehog protein is
      palmitoylated. Peptide mapping and sequencing data indicate that the palmitoyl
      group is attached to the NH2 terminus of the protein on the alpha-amino group of
      Cys-24. Cell-free palmitoylation studies demonstrate that radioactive palmitic
      acid is readily incorporated into wild type Sonic hedgehog, but not into variant
      forms lacking the Cys-24 attachment site. The lipid-tethered forms of hedgehog
      showed about a 30-fold increase in potency over unmodified soluble hedgehog in a
      cell- based (C3H10T1/2 alkaline phosphatase induction) assay, suggesting that the
      lipid tether plays an important role in hedgehog function. The observation that
      an extracellular protein such as Shh is palmitoylated is highly unusual and
      further adds to the complex nature of this protein.

PMID- 9593756
TI  - The E protein CTF4 and acetylcholine receptor expression in development and
      denervation supersensitivity.
AB  - Motor activity blocks the extrasynaptic expression of many genes in skeletal
      muscle, including those encoding ion channels, receptors, and adhesion molecules.
      Denervation reinduces transcription throughout the multinucleated myofiber,
      restoring the developmental pattern of expression, especially of the genes coding
      for the acetylcholine receptor. A screen for trans-acting factors binding to the
      enhancer region of the alpha-subunit gene of the acetylcholine receptor
      identified CTF4, a ubiquitously expressed and alternatively spliced chicken
      homologue of the human E protein transcription factor HTF4/HEB. Expression of the
      CTF4 locus closely parallels that of myogenin and acetylcholine receptor during
      development and maturation of skeletal muscle, but transcription is not similarly
      regulated by neuronal cues. Alternative splicing within the region encoding the
      transactivation domain generates two CTF4 isoforms with different tissue
      distributions, but similar binding affinities for the acetylcholine receptor
      alpha-subunit enhancer and similar transcriptional potential when complexed to
      myogenin. Direct injection of a myogenin, but not a MyoD, antisense expression
      vector into denervated skeletal muscle caused a significant decrease in the
      transcriptional activation of a depolarization-sensitive reporter gene.
      Similarly, injection of a CTF4, but less so of an E12, antisense expression
      vector impaired the denervation response, further implicating the involvement of
      a myogenin/CTF4 heterodimer in the expression of AChR genes in vivo.

PMID- 9593757
TI  - Cystic fibrosis transmembrane regulator-independent release of ATP. Its
      implications for the regulation of P2Y2 receptors in airway epithelia.
AB  - The cystic fibrosis (CF) transmembrane regulator (CFTR) is a cyclic AMP-dependent
      Cl- channel that is defective in CF cells. It has been hypothesized that CFTR
      exhibits an ATP release function that controls the airway surface ATP
      concentrations. In airway epithelial cells, CFTR-independent Ca2+-activated Cl-
      conductance is regulated by the P2Y2 receptor. Thus, ATP may function as an
      autocrine signaling factor promoting Cl- secretion in normal but not CF epithelia
      if ATP release is defective. We have tested for CFTR-dependent ATP release using
      four independent detection systems. First, a luciferase assay detected no
      differences in ATP concentrations in the medium from control versus cyclic AMP
      stimulated primary normal human nasal epithelial (HNE) cells. A marked
      accumulation of extracellular ATP resulted from mechanical stimulation effected
      by a medium displacement. Second, high pressure liquid chromatography analysis of
      3H-labeled species released from [3H]adenine-loaded HNE cells revealed no
      differences between basal and cyclic AMP-stimulated cells. Mechanical stimulation
      of HNE cells again resulted in enhanced accumulation of extracellular [3H]ATP and
      [3H]ADP. Third, when measuring ATP concentrations via nucleoside diphosphokinase
      catalyzed phosphorylation of [alpha-33P]dADP, equivalent formation of [33P]dATP
      was observed in the media of control and cyclic AMP-stimulated HNE cells and
      nasal epithelial cells from wild-type and CF mice. Mechanically stimulated
      [33P]dATP formation was similar in both cell types. Fourth, 1321N1 cells stably
      expressing the human P2Y2 receptor were used as a reporter system for detection
      of ATP via P2Y2 receptor-promoted formation of [3H]inositol phosphates. Basal
      [3H]inositol phosphate accumulation was of the same magnitude in control and CFTR
      transduced cells, and no change was observed following addition of forskolin and
      isoproterenol. In both cell types, mechanical stimulation resulted in hexokinase
      attenuable [3H]inositol phosphate formation. In summary, our data suggest that
      ATP release may be triggered by mechanical stimulation of cell surfaces. No
      evidence was found supporting a role for CFTR in the release of ATP.

PMID- 9593758
TI  - The binding of some human antiendothelial cell antibodies induces endothelial
      cell apoptosis.
AB  - The pathogenic role of antiendothelial cell antibodies (AECA) remains unclear.
      They are frequently associated with antibodies to anionic phospholipids (PL),
      such as phosphatidylserine (PS), which is difficult to reconcile with the
      distribution of PL molecular species within the plasma membrane. Since it is
      already known that PS is transferred to the outer face of the membrane as a
      preclude to apoptosis, the possibility exists that apoptosis is initiated by
      AECA. AECA-positive/anti-PL antibody-negative sera from eight patients with
      systemic sclerosis (SS) and 21 control patients were evaluated. Endothelial cells
      (EC) were incubated with AECA and the exposure of PS was established through the
      binding of annexin V. Hypoploid cell enumeration, DNA fragmentation, and optical
      and ultrastructural analyses of EC were used to confirm apoptosis. Incubation of
      EC with AECA derived from six of eight patients with SS led to the expression of
      PS on the surface of the cells. This phenomenon was significantly more frequent
      in SS (P < 0.04) than in control diseases. The redistribution of plasma membrane
      PS preceded other events associated with apoptosis: hypoploidy, DNA
      fragmentation, and morphology characteristic for apoptosis. Apoptosis-inducing
      AECA did not recognize the Fas receptor. We conclude that AECA may be pathogenic
      by inducing apoptosis.

PMID- 9593759
TI  - Biological activity of C-peptide on the skin microcirculation in patients with
      insulin-dependent diabetes mellitus.
AB  - 19 insulin-dependent diabetes mellitus (IDDM) patients participated in a
      randomized double-blind crossover investigation to investigate the impact of
      human C-peptide on skin microvascular blood flow. The investigation was also
      carried out with 10 healthy volunteers. Blood pressure, heart rate, blood sugar,
      and C-peptide levels were monitored during a 60-min intravenous infusion period
      of C-peptide (8 pmol kg-1 min-1) or saline solution (154 mmol liter-1 NaCl), and
      30 min after stopping the infusion. During the same time period, capillary blood
      cell velocity (CBV), laser Doppler flux (LDF), and skin temperature were assessed
      in the feet. In the verum arm, C-peptide levels increased after starting infusion
      to reach a maximum of 2.3+/-0.2 nmol liter-1 after 45 min, but remained below 0.
      15 nmol liter-1 during the saline treatment. Baseline CBV was lower in diabetic
      patients compared with healthy subjects (147+/-3.6 vs. 162+/-4.2 micron s-1; P <
      0.01). During C-peptide administration, CBV in IDDM patients increased
      progressively from 147+/-3.6 to 167+/-3.7 micron s-1; P < 0.001), whereas no
      significant change occurred during saline infusion or in healthy subjects. In
      contrast to the CBV measurements, the investigation of LDF, skin temperature,
      blood pressure, heart rate, or blood sugar did not demonstrate any significant
      change during the study. Replacement of human C-peptide in IDDM patients leads to
      a redistribution in skin microvascular blood flow levels comparable to levels in
      healthy subjects by increasing the nutritive CBV relative to subpapillary
      arteriovenous shunt flow.

PMID- 9593760
TI  - Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of
      the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.
AB  - The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked human genetic
      disorder characterized by mental retardation, congenital cataracts, and renal
      tubular dysfunction. The Lowe syndrome gene, OCRL1, encodes a
      phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex. The
      pathogenesis of Lowe syndrome due to deficiency of a phosphatidylinositol 4,5
      bisphosphate 5-phosphatase in the Golgi complex is unknown. We have used targeted
      disruption in embryonic stem cells to make mice deficient in Ocrl1, the mouse
      homologue for OCRL1, as an animal model for the disease. Surprisingly, mice
      deficient in Ocrl1 do not develop the congenital cataracts, renal Fanconi
      syndrome, or neurological abnormalities seen in the human disorder. We
      hypothesized that Ocrl1 deficiency is complemented in mice by inositol
      polyphosphate 5-phosphatase (Inpp5b), an autosomal gene that encodes a
      phosphatidylinositol bisphosphate 5-phosphatase highly homologous to Ocrl1. We
      created mice deficient in Inpp5b; the mice were viable and fertile without
      phenotype except for testicular degeneration in males beginning after sexual
      maturation. We crossed mice deficient in Ocrl1 to mice deficient in Inpp5b. No
      liveborn mice or embryos lacking both enzymes were found, demonstrating that
      Ocrl1 and Inpp5b have overlapping functions in mice and suggesting that the lack
      of phenotype in Ocrl1-deficient mice may be due to compensating Inpp5b function.

PMID- 9593761
TI  - Backleak, tight junctions, and cell- cell adhesion in postischemic injury to the
      renal allograft.
AB  - Postischemic injury in recipients of 3-7-d-old renal allografts was classified
      into sustained (n = 19) or recovering (n = 20) acute renal failure (ARF)
      according to the prevailing inulin clearance. Recipients of optimally
      functioning, long-standing allografts and living donors undergoing nephrectomy
      served as functional (n = 14) and structural controls (n = 10), respectively.
      Marked elevation above control of fractional clearance of dextrans of graded size
      was consistent with transtubular backleak of 57% of filtrate (inulin) in
      sustained ARF. No backleak was detected in recovering ARF. To explore a
      structural basis for backleak, allograft biopsies were taken intraoperatively, 1
      h after reperfusion in all recipients, and again on day 7 after transplant in a
      subset (n = 10). Electron microscopy revealed disruption of both apical and
      basolateral membranes of proximal tubule cells in both sustained and recovering
      ARF, but cell exfoliation and tubule basement membrane denudation were
      negligible. Histochemical analysis of membrane-associated adhesion complexes
      confirmed an abnormality of proximal but not distal tubule cells, marked in
      sustained ARF but not in recovering ARF. Staining for the zonula occludens
      complex (ZO-1) and adherens complex (alpha, beta, and gamma catenins) revealed
      diminished intensity and redistribution of each cytoskeletal protein from the
      apico-lateral membrane boundary. We conclude that impaired integrity of tight
      junctions and cell-cell adhesion in the proximal tubule provides a paracellular
      pathway through which filtrate leaks back in sustained allograft ARF.

PMID- 9593762
TI  - LPS-binding protein protects mice from septic shock caused by LPS or gram
      negative bacteria.
AB  - LPS-binding protein (LBP) recognizes bacterial LPS and transfers it to CD14,
      thereby enhancing host cell stimulation, eventually resulting in pathogenic
      states such as septic shock. Recently, LBP also was shown to detoxify LPS by
      transferring LPS into HDL particles in vitro. Thus, the predominant in vivo
      function of LBP has remained unclear. To investigate the biological activity of
      acute phase concentrations of recombinant murine LBP, high concentrations of LBP
      were investigated in vitro and in vivo. Although addition of low concentrations
      of LBP to a murine macrophage cell line enhanced LPS-induced TNF-alpha synthesis,
      acute phase concentrations of LBP blocked this effect in comparison to low-dose
      LBP. When injected into mice intraperitoneally, LBP inhibited LPS-mediated
      cytokine release and prevented hepatic failure resulting in a significantly
      decreased mortality rate in LPS-challenged and D-galactosamine-sensitized mice,
      as well as in a murine model of bacteremia. These results complement a recent
      study revealing LBP-deficient mice to be dramatically more susceptible to an
      intraperitoneal Salmonella infection as compared with normal mice. We conclude
      that acute phase LBP has a protective effect against LPS and bacterial infection
      and may represent a physiologic defense mechanism against infection. Despite the
      limitations of any murine sepsis model, the results shown may imply that LBP
      could have beneficial effects during gram-negative peritonitis in humans.

PMID- 9593763
TI  - Na-K-2Cl cotransporter gene expression and function during enterocyte
      differentiation. Modulation of Cl- secretory capacity by butyrate.
AB  - The basolateral Na-K-2Cl cotransporter (NKCC1) is a key component of the
      intestinal crypt cell secretory apparatus. Its fate during the transition to
      absorptive enterocyte and the potential impact of its altered expression on
      secretory output have not been addressed. In this report, NKCC1 mRNA was found to
      be expressed in rat jejunal crypt but not villus cells. Butyrate treatment of
      intestinal epithelial HT29 cells induced a differentiation pattern that
      recapitulated the rat intestinal crypt-villus axis, with NKCC1 mRNA levels
      decreasing in a time- and dose-dependent fashion in parallel with upregulation of
      apical brush-border markers. Butyrate but not acetate or proprionate decreased
      basal and cAMP-stimulated bumetanide-sensitive K+ (86Rb) uptake in both HT29
      cells and the Cl--secreting T84 line. Butyrate markedly decreased transepithelial
      Cl- secretion in confluent T84 monolayers without effect on cAMP-regulated apical
      Cl- efflux. We conclude that NKCC1 regulation during enterocyte differentiation
      occurs at the level of gene expression, and that selective downregulation of
      NKCC1 gene expression and function by butyrate leads to a profound decrease in
      transepithelial Cl- secretion. These data emphasize the importance of NKCC1 in
      determining epithelial secretory capacity and suggest the possibility of
      modulation of the enterocytic transport phenotype as therapy for diarrheal
      disorders.

PMID- 9593764
TI  - The B1-agonist [des-Arg10]-kallidin activates transcription factor NF-kappaB and
      induces homologous upregulation of the bradykinin B1-receptor in cultured human
      lung fibroblasts.
AB  - The bradykinin B1-receptor is strongly upregulated under chronic inflammatory
      conditions. However, the mechanism and reason are not known. Because a better
      understanding of the mechanism of the upregulation will help in understanding its
      potential importance in inflammation, we have studied the molecular mechanism of
      B1-receptor upregulation in cultured human lung fibroblasts (IMR 90) in response
      to IL-1beta and the B1-agonist [des-Arg10]-kallidin. We show that treatment of
      human IMR 90 cells by IL-1beta stimulates the expression of both B1-receptor mRNA
      and protein. The latter was studied by Western blot analysis using antipeptide
      antibodies directed against the COOH-terminal part of the human B1-receptor. We
      furthermore report the novel observation that the B1-receptor is upregulated by
      its own agonist which was completely blocked by the specific B1-antagonist [des
      Arg10-Leu9]-kallidin, indicating an upregulation entirely mediated through cell
      surface B1-receptors. The increased population of B1-receptors was functionally
      coupled as exemplified by an enhancement of the B1-agonist induced increase in
      free cytosolic calcium. Upregulation by the B1-agonist was blocked by a specific
      protein kinase C inhibitor. B1-agonist-induced upregulation was correlated to the
      induction of transcription factor nuclear factor kappaB (NF-kappaB) which
      efficiently bound to the NF-kappaB-like sequence located in the promoter region
      of the human B1-receptor gene. This correlation was further confirmed by reporter
      gene assays which showed that this NF-kappaB-like sequence, in the B1-receptor
      promoter context, could contribute to IL-1beta and DLBK-induced B1-receptor
      transcription activation, and by the effect of NF-kappaB inhibitor
      pyrrolidinedithiocarbamate which diminished both B1-receptor upregulation and NF
      kappaB activation. NF-kappaB is now recognized as a key inflammatory mediator
      which is activated by the B1-agonist but which is also involved in B1-receptor
      upregulation.

PMID- 9593765
TI  - Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity
      of critical transcription factors.
AB  - Sodium-dependent uptake of bile acids across the hepatic basolateral membrane is
      rapidly and profoundly diminished during sepsis, thus contributing to the
      pathogenesis of sepsis-associated cholestasis. This effect is mediated by
      endotoxin or effector cytokines, which reduce expression of several hepatobiliary
      transporters, including the sodium-dependent bile acid transporter gene, ntcp. We
      test here the hypothesis that endotoxin treatment leads to impaired binding
      activity of ntcp promoter trans-acting factors, resulting in reduction of ntcp
      mRNA expression. After endotoxin administration, ntcp mRNA levels reached their
      nadir by 16 h, and nuclear run-on assays demonstrated a marked reduction in ntcp
      gene transcription. At 16 h after treatment, nuclear binding activities of two
      key factors that transactivate the ntcp promoter, hepatocyte nuclear factor (HNF)
      1 and Footprint B binding protein (FpB BP), decreased to 44 and 47% of
      pretreatment levels, respectively, while levels of the other known ntcp promoter
      transactivator, signal transducer and activator of transcription 5, were
      unaffected. In contrast, the universal inflammatory response factors nuclear
      factor kappaB and activating protein 1 were both upregulated significantly.
      Examination of nuclear extracts obtained at sequential time points revealed that
      the maximal decrease in nuclear activities of both HNF1 and FpB BP preceded the
      nadir of ntcp mRNA expression by 6-10 h. Furthermore, these two nuclear factors
      returned towards normal levels before the recovery of ntcp mRNA levels observed
      by 48 h. Since HNF1alpha mRNA levels were unchanged at all time points, HNF1 is
      likely to be regulated posttranscriptionally by endotoxin. We conclude that the
      downregulation of ntcp gene expression by endotoxin is mediated at the level of
      transcription through tandem reductions in the nuclear binding activity of two
      critical transcription factors. These findings provide new insight into the
      coordinated downregulation of hepatobiliary transporters during sepsis.

PMID- 9593766
TI  - Vascular expression of extracellular superoxide dismutase in atherosclerosis.
AB  - We characterized a novel form of extracellular superoxide dismutase (ecSOD) in
      atherosclerotic vessels. Specific activity and protein expression of ecSOD was
      increased two- to threefold in apo E-deficient compared with control aortas.
      RNase protection assays demonstrated that the expected ecSOD transcript was not
      increased in either apo E-deficient mice or cholesterol-fed LDL receptor
      deficient mice, but that a second, lower molecular weight transcript was present
      and became predominant as atherosclerosis progressed. Sequence analysis revealed
      that this novel ecSOD has a 10-bp deletion in the 3' untranslated region and an
      asparagine to aspartic acid mutation at amino acid 21. Studies of isolated
      macrophages and immunohistochemistry suggested that the truncated ecSOD
      transcript was expressed by lipid-laden but not control macrophages. Recombinant
      wild-type and novel ecSODs expressed in Sf9 cells exhibited similar SOD
      activities. These experiments show that ecSOD expression is increased in
      atherosclerotic vessels and that this is characterized by an alteration in mRNA
      and protein structure. Further, the source of this altered ecSOD is likely the
      lipid-laden macrophage. The enzymatic properties of this novel ecSOD may have
      important implications for the function of the lipid-laden macrophage and the
      atherosclerotic process.

PMID- 9593767
TI  - Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its
      involvement in pancreatic islet and beta cell development during the perinatal
      period.
AB  - Mutation of the murine maturity-onset diabetes mellitus of the young (Mody) locus
      induces diabetes, but the effects of its homozygosity on the pancreas remain
      unknown. F2 mice were obtained by F1 (diabetic C57BL6 x normal Mus musculus
      castaneus) crosses. About 20% of the F2 progeny developed diabetes by 2 wk of
      age, 50% of the progeny were normal at 2 wk and developed diabetes between 5 and
      8 wk of age, and the remaining 30% did not develop diabetes. Quantitative trait
      locus analysis using blood glucose levels of 118 F2 mice at 2 wk of age and 5-8
      wk of age located Mody within 3 cM of D7Mit258. Histopathological investigation
      revealed hypoplastic islets (approximately 33% of that of wild-type mice) and a
      lower density of beta cells (approximately 20% of wild-type) with a reciprocal
      dominance of alpha cells (four times that of wild-type) in Mody homozygotes.
      Electron microscopic observations revealed a specific decrease in the number of
      insulin secretory granules and a lower density of beta cells. Ratios of insulin
      to glucagon contents confirmed specific decreases in insulin content: 0.01 for
      homozygotes, 0.54 for heterozygotes, and 1.11 for wild-type mice on day 14. These
      results suggest that Mody is involved in both islet growth and beta cell
      function.

PMID- 9593768
TI  - High efficiency myogenic conversion of human fibroblasts by adenoviral vector
      mediated MyoD gene transfer. An alternative strategy for ex vivo gene therapy of
      primary myopathies.
AB  - Ex vivo gene therapy of primary myopathies, based on autologous transplantation
      of genetically modified myogenic cells, is seriously limited by the number of
      primary myogenic cells that can be isolated, expanded, transduced, and
      reimplanted into the patient's muscles. We explored the possibility of using the
      MyoD gene to induce myogenic conversion of nonmuscle, primary cells in a
      quantitatively relevant fashion. Primary human and murine fibroblasts from skin,
      muscle, or bone marrow were infected by an E1-deleted adenoviral vector carrying
      a retroviral long terminal repeat-promoted MyoD cDNA. Expression of MyoD caused
      irreversible withdrawal from the cell cycle and myogenic differentiation in the
      majority (from 60 to 90%) of cultured fibroblasts, as defined by activation of
      muscle-specific genes, fusion into contractile myotubes, and appearance of
      ultrastructurally normal sarcomagenesis in culture. 24 h after adenoviral
      exposure, MyoD-converted cultures were injected into regenerating muscle of
      immunodeficient (severe combined immunodeficiency/beige) mice, where they gave
      rise to beta-galactosidase positive, centrally nucleated fibers expressing human
      myosin heavy chains. Fibers originating from converted fibroblasts were
      indistinguishable from those obtained by injection of control cultures of lacZ
      transduced satellite cells. MyoD-converted murine fibroblasts participated to
      muscle regeneration also in immunocompetent, syngeneic mice. Although antibodies
      from these mice bound to adenoviral infected cells in vitro, no inflammatory
      infiltrate was present in the graft site throughout the 3-wk study period. These
      data support the feasibility of an alternative approach to gene therapy of
      primary myopathies, based on implantation of large numbers of genetically
      modified primary fibroblasts massively converted to myogenesis by adenoviral
      delivery of MyoD ex vivo.

PMID- 9593769
TI  - Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in
      asthma.
AB  - Airway hyperresponsiveness leading to subepithelial fibrosis is mediated by
      inflammatory cells activated by T helper (Th) 2-derived cytokines such as IL-4
      and IL-5. By analyzing the phenotype and response of human lung fibroblasts
      derived from either fetal (ICIG7) or adult (CCL202) tissue as well as from a Th2
      type stromal reaction (FPA) to IL-4 and IL-13, we provide evidence that human
      lung fibroblasts may behave as inflammatory cells upon activation by IL-4 and IL
      13. We show that the three types of fibroblasts constitute different populations
      that display a distinct pattern in cell surface molecule expression and
      proinflammatory cytokine and chemokine release. All fibroblasts express
      functional but different IL-4/IL-13 receptors. Thus, while IL-4 receptor (R)
      alpha and IL-13Ralpha1 chains are present in all the cells, CCL202 and FPA
      fibroblasts coexpress the IL-13Ralpha2 and the IL-2Rgamma chain, respectively,
      suggesting the existence of a heterotrimeric receptor (IL-4Ralpha/IL-13Ralpha/IL
      2Rgamma) able to bind IL-4 and IL-13. Stimulation with IL-4 or IL-13 triggers in
      the fibroblasts a differential signal transduction and upregulation in the
      expression of beta1 integrin and vascular cell adhesion molecule 1 and in the
      production of IL-6 and monocyte chemoattractant protein 1, two inflammatory
      cytokines important in the pathogenesis of allergic inflammation. Our results
      suggest that when activated by IL-4 and IL-13, different subsets of lung
      fibroblasts may act as effector cells not only in the pathogenesis of asthma but
      also in lung remodeling processes. They may also differentially contribute to
      trigger and maintain the recruitment, homing, and activation of inflammatory
      cells.

PMID- 9593770
TI  - Receptor-mediated endocytosis of albumin by kidney proximal tubule cells is
      regulated by phosphatidylinositide 3-kinase.
AB  - Receptor-mediated endocytosis of albumin is an important function of the kidney
      proximal tubule epithelium. We have measured endocytosis of [125I]-albumin in
      opossum kidney cells and examined the regulation of this process by
      phosphatidylinositide 3-kinase (PI 3-kinase). Albumin endocytosis was inhibited
      by both wortmannin (IC50 6.9 nM) and LY294002 (IC50 6.5 microM) at concentrations
      that suggested the involvement of PI 3-kinase in its regulation. Recycling rates
      were unaffected. We transfected OK cells with either a wild-type p85 subunit of
      PI 3-kinase, or a dominant negative form of the p85 subunit (Deltap85) using the
      LacSwitch expression system. Transfects were screened by immunoblotting with anti
      PI 3-kinase antibodies. Under basal conditions, transfects demonstrated no
      expression of p85 or Deltap85, but expression was briskly induced by treatment of
      the cells with IPTG (EC50 13.7 microM). Inhibition of PI 3-kinase activity by
      Deltap85 was confirmed by in vitro kinase assay of anti-phosphotyrosine
      immunoprecipitates from transfected cells stimulated with insulin. Expression of
      Deltap85 resulted in marked inhibition of albumin endocytosis, predominantly as a
      result of reduction of the Vmax of the transport process. Expression of p85 had
      no significant effect on albumin uptake. The results demonstrate that PI 3-kinase
      regulates an early step in the receptor-mediated endocytosis of albumin by kidney
      proximal tubular cells.

PMID- 9593771
TI  - Increased expression of apolipoprotein E in transgenic rabbits results in reduced
      levels of very low density lipoproteins and an accumulation of low density
      lipoproteins in plasma.
AB  - Transgenic rabbits expressing human apo E3 were generated to investigate
      mechanisms by which apo E modulates plasma lipoprotein metabolism. Compared with
      nontransgenic littermates expressing approximately 3 mg/dl of endogenous rabbit
      apo E, male transgenic rabbits expressing approximately 13 mg/dl of human apo E
      had a 35% decrease in total plasma triglycerides that was due to a reduction in
      VLDL levels and an absence of large VLDL. With its greater content of apo E,
      transgenic VLDL had an increased binding affinity for the LDL receptor in vitro,
      and injected chylomicrons were cleared more rapidly by the liver in transgenic
      rabbits. In contrast to triglyceride changes, transgenic rabbits had a 70%
      increase in plasma cholesterol levels due to an accumulation of LDL and apo E
      rich HDL. Transgenic and control LDL had the same binding affinity for the LDL
      receptor. Both transgenic and control rabbits had similar LDL receptor levels,
      but intravenously injected human LDL were cleared more slowly in transgenic
      rabbits than in controls. Changes in lipoprotein lipolysis did not contribute to
      the accumulation of LDL or the reduction in VLDL levels. These observations
      suggest that the increased content of apo E3 on triglyceride-rich remnant
      lipoproteins in transgenic rabbits confers a greater affinity for cell surface
      receptors, thereby increasing remnant clearance from plasma. The apo E-rich large
      remnants appear to compete more effectively than LDL for receptor-mediated
      binding and clearance, resulting in delayed clearance and the accumulation of LDL
      in plasma.

PMID- 9593772
TI  - Insulin-like growth factor system abnormalities in hepatitis C-associated
      osteosclerosis. Potential insights into increasing bone mass in adults.
AB  - Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by
      a marked increase in bone mass during adult life. Despite the rarity of HCAO,
      understanding the mediator(s) of the skeletal disease is of great interest. The
      IGFs-I and -II have potent anabolic effects on bone, and alterations in the IGFs
      and/or IGF-binding proteins (IGFBPs) could be responsible for the increase in
      bone formation in this disorder. Thus, we assayed sera from seven cases of HCAO
      for IGF-I, IGF-II, IGF-IIE (an IGF-II precursor), and IGFBPs. The distribution of
      the serum IGFs and IGFBPs between their ternary ( approximately 150 kD) and
      binary (approximately 50 kD) complexes was also determined to assess IGF
      bioavailability. HCAO patients had normal serum levels of IGF-I and -II, but had
      markedly elevated levels of IGF-IIE. Of the IGFBPs, an increase in IGFBP-2 was
      unique to these patients and was not found in control hepatitis C or hepatitis B
      patients. IGF-I and -II in sera from patients with HCAO were carried, as in the
      case of sera from control subjects, bound to IGFBP-3 in the approximately 150-kD
      complex, which is retained in the circulation. However, IGF-IIE was predominantly
      in the approximately 50-kD complex in association with IGFBP-2; this complex can
      cross the capillary barrier and access target tissues. In vitro, we found that
      IGF-II enhanced by over threefold IGFBP-2 binding to extracellular matrix
      produced by human osteoblasts and that in an extracellular matrix-rich
      environment, the IGF-II/IGFBP-2 complex was as effective as IGF-II alone in
      stimulating human osteoblast proliferation. Thus, IGFBP-2 may facilitate the
      targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO
      patients, with a subsequent stimulation by IGFs of osteoblast function. Our
      findings in HCAO suggest a possible means to increase bone mass in patients with
      osteoporosis.

PMID- 9593773
TI  - Glucocorticoid exposure in late gestation permanently programs rat hepatic
      phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and
      causes glucose intolerance in adult offspring.
AB  - Low birth weight in humans is predictive of insulin resistance and diabetes in
      adult life. The molecular mechanisms underlying this link are unknown but fetal
      exposure to excess glucocorticoids has been implicated. The fetus is normally
      protected from the higher maternal levels of glucocorticoids by feto-placental
      11beta-hydroxysteroid dehydrogenase type-2 (11beta-HSD2) which inactivates
      glucocorticoids. We have shown previously that inhibiting 11beta-HSD2 throughout
      pregnancy in rats reduces birth weight and causes hyperglycemia in the adult
      offspring. We now show that dexamethasone (a poor substrate for 11beta-HSD2)
      administered to pregnant rats selectively in the last week of pregnancy reduces
      birth weight by 10% (P < 0.05), and produces adult fasting hyperglycemia (treated
      5.3+/-0.3; control 4.3+/-0.2 mmol/ liter, P = 0.04), reactive hyperglycemia
      (treated 8.7+/-0.4; control 7.5+/-0.2 mmol/liter, P = 0.03), and hyperinsulinemia
      (treated 6.1+/-0.4; control 3.8+/-0.5 ng/ml, P = 0.01) on oral glucose loading.
      In the adult offspring of rats exposed to dexamethasone in late pregnancy,
      hepatic expression of glucocorticoid receptor (GR) mRNA and phosphoenolpyruvate
      carboxykinase (PEPCK) mRNA (and activity) are increased by 25% (P = 0.01) and 60%
      (P < 0.01), respectively, while other liver enzymes (glucose-6-phosphatase,
      glucokinase, and 11beta-hydroxysteroid dehydrogenase type-1) are unaltered. In
      contrast dexamethasone, when given in the first or second week of gestation, has
      no effect on offspring insulin/glucose responses or hepatic PEPCK and GR
      expression. The increased hepatic GR expression may be crucial, since rats
      exposed to dexamethasone in utero showed potentiated glucose responses to
      exogenous corticosterone. These observations suggest that excessive
      glucocorticoid exposure late in pregnancy predisposes the offspring to glucose
      intolerance in adulthood. Programmed hepatic PEPCK overexpression, perhaps
      mediated by increased GR, may promote this process by increasing gluconeogenesis.

PMID- 9593774
TI  - Direct evidence that protein kinase C plays an essential role in the development
      of late preconditioning against myocardial stunning in conscious rabbits and that
      epsilon is the isoform involved.
AB  - Brief ischemic episodes confer marked protection against myocardial stunning 1-3
      d later (late preconditioning [PC] against stunning). The mechanism of this
      powerful protective effect is poorly understood. Although protein kinase C (PKC)
      has been implicated in PC against infarction, it is unknown whether it triggers
      late PC against stunning. In addition, the entire PKC hypothesis of ischemic PC
      remains controversial, possibly because the effects of PKC inhibitors on PC
      protection have not been correlated with their effects on PKC activity and/or
      translocation in vivo. Thus, conscious rabbits underwent a sequence of six 4-min
      coronary occlusion (O)/4-min reperfusion (R) cycles for three consecutive days
      (days 1, 2, and 3). In the control group (group I, n = 7), the recovery of
      systolic wall thickening after the six O/R cycles was markedly improved on days 2
      and 3 compared with day 1, indicating the development of late PC against
      stunning. Administration of the PKC inhibitor chelerythrine at a dose of 5 mg/kg
      before the first O on day 1 (group II, n = 10) abrogated the late PC effect
      against stunning, whereas a 10-fold lower dose (0.5 mg/kg; group III, n = 7) did
      not. Administration of 5 mg/kg of chelerythrine 10 min after the sixth
      reperfusion on day 1 (group IV, n = 6) failed to block late PC against stunning.
      When rabbits were given 5 mg/kg of chelerythrine in the absence of O/R (group V,
      n = 5), the severity of myocardial stunning 24 h later was not modified.
      Pretreatment with phorbol 12-myristate 13-acetate (4 microg/kg) on day 1 without
      ischemia (group VI, n = 11) induced late PC against stunning on day 2 and the
      magnitude of this effect was equivalent to that observed after ischemic PC. In
      vehicle-treated rabbits (group VIII, n = 5), the six O/R cycles caused
      translocation of PKC isoforms epsilon and eta from the cytosolic to the
      particulate fraction without significant changes in total PKC activity, in the
      subcellular distribution of total PKC activity, or in the subcellular
      distribution of the alpha, beta1, beta2, gamma, delta, zeta, iota, lambda, and mu
      isoforms. The higher dose of chelerythrine (5 mg/kg; group X, n = 5) prevented
      the translocation of both PKC epsilon and eta induced by ischemic PC, whereas the
      lower dose (0.5 mg/kg; group XI, n = 5) prevented the translocation of PKC eta
      but not that of epsilon, indicating that the activation of epsilon is necessary
      for late PC to occur whereas that of eta is not. To our knowledge, this is the
      first demonstration that a PKC inhibitor actually prevents the translocation of
      PKC induced by ischemic PC in vivo, and that this inhibition of PKC translocation
      results in loss of PC protection. Taken together, the results demonstrate that
      the mechanism of late PC against myocardial stunning in conscious rabbits
      involves a PKC-mediated signaling pathway, and implicate epsilon as the specific
      PKC isoform responsible for the development of this cardioprotective phenomenon.

PMID- 9593775
TI  - Structure-function of recombinant Na/H exchanger regulatory factor (NHE-RF).
AB  - Inhibition of the renal brush border membrane (BBM) Na/H exchanger by cAMP
      dependent protein kinase, PKA, requires participation of a recently cloned
      regulatory cofactor, Na/H exchanger-regulatory factor (NHE-RF). As deduced from
      the cDNA of this 358-amino acid protein, amino acids 11-101 and amino acids 150
      241 of the NHE-RF protein share 74% overall homology suggesting duplication of
      these PDZ containing domains. The serine residues at amino acid position 289 and
      340 are considered to be the most likely sites for PKA mediated phosphorylation.
      To study the structure- function relation between NHE-RF and PKA mediated
      inhibition of the rabbit BBM Na/H exchanger, the effect of recombinant proteins
      representing full-length NHE-RF as well as truncated and mutant forms of NHE-RF
      were determined using a reconstitution assay. The reconstitution assay employed a
      fraction of rabbit BBM proteins that contains Na/H exchanger activity that is not
      regulated by PKA. NHE-RF in the presence of ATP and Mg but not PKA, inhibited
      Na/H exchange activity in a concentration-dependent manner. In the presence of
      PKA, there was a significant left shift in the dose-response relation such that
      10(-12) M NHE-RF inhibited Na/H exchange transport by 30% in the presence but not
      in the absence of PKA. A recombinant polypeptide representing amino acids 1-151
      (Domain I) did not affect Na/H exchange transport in the presence or absence of
      PKA. A polypeptide representing amino acids 149-358 (Domain II) in the presence
      of ATP and Mg but not PKA, inhibited Na/H exchange activity in a concentration
      dependent manner. In the presence of PKA, there was a left shift in the dose
      response relation. 10(-12) M of Domain II polypeptide inhibited transport by 18%
      in the presence but not in the absence of PKA. Mutation of serine residues 287,
      289, and 290 to alanine did not affect the inhibitory effect in the absence of
      PKA but abolished the left shift in the dose-response relation elicited by PKA.
      Mutation of serine residues 339 and 340 to alanine were without effect on PKA
      dependent regulation of Na/H exchange transport. These studies indicate that NHE
      RF inhibits basal rabbit renal BBM Na/H exchange activity-an effect which is
      augmented by PKA. The amino acid sequences in the polypeptide containing only the
      NH2-terminal PDZ domain of NHE-RF have no intrinsic activity as an inhibitor but
      appears to be required for the full-length NHE-RF to express its full inhibitory
      effect on the BBM Na/H exchanger. One or more of the serine residues at positions
      287, 289, and/or 290 represent the critical PKA phosphorylation site(s) on the
      NHE-RF protein that mediates the physiologic effect of cAMP on the renal BBM Na/H
      exchanger.

PMID- 9593776
TI  - Role of nitric oxide and peroxynitrite in the cytokine-induced sustained
      myocardial dysfunction in dogs in vivo.
AB  - Studies in vitro suggested that inflammatory cytokines could cause myocardial
      dysfunction. However, the detailed mechanism for the cytokine-induced myocardial
      dysfunction in vivo remains to be examined. We thus examined this point in our
      new canine model in vivo, in which microspheres with and without IL-1beta were
      injected into the left main coronary artery. Left ventricular ejection fraction
      (LVEF) was evaluated by echocardiography for 1 wk. Immediately after the
      microsphere injection, LVEF decreased to approximately 30% in both groups. While
      LVEF rapidly normalized in 2 d in the control group, it was markedly impaired in
      the IL-1beta group even at day 7. Pretreatment with dexamethasone or with
      aminoguanidine, an inhibitor of inducible nitric oxide synthase, prevented the IL
      1beta-induced myocardial dysfunction. Nitrotyrosine concentration, an in vivo
      marker of the peroxynitrite production by nitric oxide and superoxide anion, was
      significantly higher in the myocardium of the IL-1beta group than in that of the
      control group or the group cotreated with dexamethasone or aminoguanidine. There
      was an inverse linear relationship between myocardial nitrotyrosine
      concentrations and LVEF. These results indicate that IL-1beta induces sustained
      myocardial dysfunction in vivo and that nitric oxide produced by inducible nitric
      oxide synthase and the resultant formation of peroxynitrite are substantially
      involved in the pathogenesis of the cytokine-induced sustained myocardial
      dysfunction in vivo.

PMID- 9593777
TI  - Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.
AB  - Mutations in the gene for the transcription factor hepatocyte nuclear factor
      (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of
      diabetes that results from defects in insulin secretion. Since the nature of
      these defects has not been defined, we compared insulin secretory function in
      heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null
      mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha
      (+/+)]. Blood glucose concentrations were similar in HNF-1alpha (+/+) and (+/-)
      mice (7.8+/-0.2 and 7.9+/-0.3 mM), but were significantly higher in the HNF
      1alpha (-/-) mice (13.1+/-0.7 mM, P < 0.001). Insulin secretory responses to
      glucose and arginine in the perfused pancreas and perifused islets from HNF
      1alpha (-/-) mice were < 15% of the values in the other two groups and were
      associated with similar reductions in intracellular Ca2+ responses. These defects
      were not due to a decrease in glucokinase or insulin gene transcription. beta
      cell mass adjusted for body weight was not reduced in the (-/-) animals, although
      pancreatic insulin content adjusted for pancreas weight was slightly lower
      (0.06+/-0.01 vs. 0.10+/-0.01 microg/mg, P < 0.01) than in the (+/+) animals. In
      summary, a null mutation in the HNF-1alpha gene in homozygous mice leads to
      diabetes due to alterations in the pathways that regulate beta cell responses to
      secretagogues including glucose and arginine. These results provide further
      evidence in support of a key role for HNF-1alpha in the maintenance of normal
      beta cell function.

PMID- 9593778
TI  - Hyperresponsiveness of vitamin D receptor gene expression to 1,25
      dihydroxyvitamin D3. A new characteristic of genetic hypercalciuric stone-forming
      rats.
AB  - Hypercalciuria in genetic hypercalciuric stone-forming (GHS) rats is accompanied
      by intestinal Ca hyperabsorption with normal serum 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] levels, elevation of intestinal, kidney, and bone vitamin D
      receptor (VDR) content, and greater 1,25(OH)2D3-induced bone resorption in vitro.
      To test the hypothesis that hyperresponsiveness of VDR gene expression to
      1,25(OH)2D3 may mediate these observations, male GHS and wild-type Sprague-
      Dawley normocalciuric control rats were fed a normal Ca diet (0.6% Ca) and
      received a single intraperitoneal injection of either 1,25(OH)2D3 (10-200 ng/100
      g body wt) or vehicle. Total RNAs were isolated from both duodenum and kidney
      cortex, and the VDR and calbindin mRNA levels were determined by Northern blot
      hybridization using specific cDNA probes. Under basal conditions, VDR mRNA levels
      in GHS rats were lower in duodenum and higher in kidney compared with wild-type
      controls. Administration of 1,25(OH)2D3 increased VDR gene expression
      significantly in GHS but not normocalciuric animals, in a time- and dose
      dependent manner. In vivo half-life of VDR mRNA was similar in GHS and control
      rats in both duodenum and kidney, and was prolonged significantly (from 4-5 to >
      8 h) by 1,25(OH)2D3 administration. Neither inhibition of gene transcription by
      actinomycin D nor inhibition of de novo protein synthesis with cycloheximide
      blocked the upregulation of VDR gene expression stimulated by 1,25(OH)2D3
      administration. No alteration or mutation was detected in the sequence of
      duodenal VDR mRNA from GHS rats compared with wild-type animals. Furthermore,
      1,25(OH)2D3 administration also led to an increase in duodenal and renal
      calbindin mRNA levels in GHS rats, whereas they were either suppressed or
      unchanged in wild-type animals. The results suggest that GHS rats hyperrespond to
      minimal doses of 1,25(OH)2D3 by an upregulation of VDR gene expression. This
      hyperresponsiveness of GHS rats to 1,25(OH)2D3 (a) occurs through an increase in
      VDR mRNA stability without involving alteration in gene transcription, de novo
      protein synthesis, or mRNA sequence; and (b) is likely of functional
      significance, and affects VDR-responsive genes in 1, 25(OH)2D3 target tissues.
      This unique characteristic suggests that GHS rats may be susceptible to minimal
      fluctuations in serum 1, 25(OH)2D3, resulting in increased VDR and VDR-responsive
      events, which in turn may pathologically amplify the actions of 1,25(OH)2D3 on Ca
      metabolism that thus contribute to the hypercalciuria and stone formation.

PMID- 9593779
TI  - Insulin therapy in burn patients does not contribute to hepatic triglyceride
      production.
AB  - Lipid kinetics were studied in six severely burned patients who were treated with
      a high dose of exogenous insulin plus glucose to promote protein metabolism. The
      patients were 20+/-2-yr-old (SD) with 63+/-8% total body surface area burned.
      They were studied in a randomized order (a) in the fed state on the seventh day
      of a control period (C) of continuous high-carbohydrate enteral feeding alone,
      and (b) on the seventh day of enteral feeding plus exogenous insulin (200 pmol/h
      = 28 U/h) with extra glucose given as needed to avoid hypoglycemia (I+G). Despite
      a glucose delivery rate approximately 100% in excess of energy requirements, the
      following lipid parameters were unchanged: (a) total hepatic VLDL triglyceride
      (TG) secretion rate (0.165+/-0.138 [C] vs. 0.154+/- 0.138 mmol/kg . d-1 [I+G]),
      (b) plasma TG concentration (1.58+/-0.66 [C] vs. 1. 36+/-0.41 mmol/liter [I+G]),
      and (c) plasma VLDL TG concentration (0. 68+/-0.79 [C] vs. 0.67+/- 0.63
      mmol/liter [I+G]). Instead, the high-carbohydrate delivery in conjunction with
      insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL
      TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of
      palmitate from lipolysis. In association with the doubling of the secretion rate
      of de novo-synthesized fatty acid (FA) in VLDL TG during insulin therapy (P >
      0.5), the relative amount of palmitate and stearate increased from 35+/-5 to 44+/
      8% and 4+/-1 to 7+/-2%, respectively, in VLDL TG, while the relative
      concentration of oleate and linoleate decreased from 43+/-5 to 37+/-6% and 8+/-4%
      to 2+/-2%, respectively. A 15-fold increase in plasma insulin concentration did
      not change the rate of release of FA into plasma (8.22+/-2.86 [C] vs. 8.72+/-6.68
      mmol/kg.d-1 [I+G]. The peripheral release of FA represents a far greater
      potential for hepatic lipid accumulation in burn patients than the endogenous
      hepatic fat synthesis, even during excessive carbohydrate intake in conjunction
      with insulin therapy.

PMID- 9593780
TI  - A new animal model for studying Lyme disease spirochetes in a mammalian host
      adapted state.
AB  - There is now substantial evidence that Borrelia burgdorferi, the Lyme disease
      spirochete, undergoes major alterations in antigenic composition as it cycles
      between its arthropod and mammalian hosts. In this report, we cultivated B.
      burgdorferi 297 within dialysis membrane chambers implanted into the peritoneal
      cavities of rats to induce antigenic changes similar to those which occur during
      mammalian infection. Chamber-grown spirochetes, which remained fully virulent,
      did not express either outer surface protein A or Lp6.6, lipoproteins known to be
      downregulated after mammalian infection. However, they did, express p21, a well
      characterized outer surface protein E homologue, which is selectively expressed
      during infection. SDS-PAGE, two-dimensional gel electrophoresis, and immunoblot
      analysis revealed that chamber-grown borreliae also expressed uncharacterized
      proteins not expressed by in vitro-cultivated spirochetes; reactivity with sera
      from mice chronically infected with B. burgdorferi 297 confirmed that many of
      these novel proteins are selectively expressed during experimental murine
      infection. Finally, we used differential display RT-PCR to identify transcripts
      of other differentially expressed B. burgdorferi genes. One gene (2.9-7lpB)
      identified with this technique belongs to a family of genes located on homologous
      32- and 18-kb circular plasmids. The lipoprotein encoded by 2.9-7lpB was shown to
      be selectively expressed by chamber-grown spirochetes and by spirochetes during
      experimental infection. Cultivation of B. burgdorferi in rat peritoneal implants
      represents a novel system for studying Lyme disease spirochetes in a mammalian
      host-adapted state.

PMID- 9593781
TI  - Postabsorptive respiratory quotient and insulin-stimulated glucose storage rate
      in nondiabetic pima indians are related To glycogen synthase fractional activity
      in cultured myoblasts.
AB  - A decreased ratio of fat to carbohydrate oxidation rate (an elevated respiratory
      quotient) predicts the development of obesity. Skeletal muscle accounts for a
      major fraction of total body lipid oxidation and is the principle site for
      reduced glucose storage in insulin-resistant subjects. The potentially important
      role that muscle has in promoting obesity or insulin resistance may be based on
      metabolic control intrinsic to skeletal muscle. Cultured skeletal muscle provides
      a system to examine the importance of inherent metabolic traits in muscle
      biopsies from obese and insulin-resistant subjects. Glycogen synthase fractional
      activity (GSFA) was measured in cultured myoblasts from 21 Pima Indians
      characterized in vivo using indirect calorimetry and a euglycemic
      hyperinsulinemic clamp. Basal GSFA in cultured muscle cells is inversely
      correlated with postabsorptive respiratory quotient of the muscle donors (r = 
      0.66, P = 0.001) and with in vivo high dose insulin-stimulated glucose storage
      rates (r = 0.47, P = 0.04). These results indicate that the postabsorptive
      respiratory quotients and insulin-mediated glucose storage rates in vivo share a
      common regulatory mechanism with GSFA in cultured myoblasts. Abnormal regulation
      of glycogen synthase phosphorylation state may be an intrinsic defect in skeletal
      muscle associated with obesity and insulin resistance.

PMID- 9593782
TI  - Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and
      correction by chemical chaperones.
AB  - Five single-point aquaporin-2 (AQP2) mutations that cause non-X-linked
      nephrogenic diabetes insipidus (NDI) were characterized to establish the cellular
      defect and to develop therapeutic strategies. In Xenopus oocytes expressing AQP2
      cRNAs, single-channel water permeabilities of mutants L22V, T126M, and A147T were
      similar to that of wild-type AQP2, whereas R187C and C181W were nonfunctional. In
      [35S]methionine pulse-chase experiments in transiently transfected CHO cells,
      half-times for AQP2 degradation were approximately 4 h for wild-type AQP2 and
      L22V, and mildly decreased for T126M (2.7 h), C181W (2.4 h), R187C (2.0 h), and
      A147T (1.8 h). Immunofluorescence showed three distinct AQP2-staining patterns:
      plasma membrane and endosomal staining (wild-type, L22V), endoplasmic reticulum
      (ER) staining (T126M > A147T approximately R187C), or a mixed pattern of
      reticular and perinuclear vesicular staining. Immunoblot of fractionated vesicles
      confirmed primary ER localization of T126M, R187C, and A147T. To determine if the
      AQP2-trafficking defect is correctable, cells were incubated with the "chemical
      chaperone" glycerol for 48 h. Immunoblot showed that glycerol produced a nearly
      complete redistribution of AQP2 (T126M, A147T, and R187C) from ER to
      membrane/endosome fractions. Immunofluorescence confirmed the cellular
      redistribution. Redistribution of AQP2 mutants was also demonstrated in
      transfected MDCK cells, and using the chaperones TMAO and DMSO in place of
      glycerol in CHO cells. Water permeability measurements indicated that functional
      correction was achieved. These results indicate defective mammalian cell
      processing of mutant AQP2 water channels in NDI, and provide evidence for
      pharmacological correction of the processing defect by chemical chaperones.

PMID- 9593783
TI  - A pathogenetic role for the thymoma in myasthenia gravis. Autosensitization of IL
      4- producing T cell clones recognizing extracellular acetylcholine receptor
      epitopes presented by minority class II isotypes.
AB  - Myasthenia gravis (MG) is caused by helper T cell-dependent autoantibodies
      against the muscle acetylcholine receptor (AChR). Thymic epithelial tumors
      (thymomas) occur in 10% of MG patients, but their autoimmunizing potential is
      unclear. They express mRNAs encoding AChR alpha and epsilon subunits, and might
      aberrantly select or sensitize developing thymocytes or recirculating peripheral
      T cells against AChR epitopes. Alternatively, there could be defective self
      tolerance induction in the abundant maturing thymocytes that they usually
      generate. For the first time, we have isolated and characterized AChR-specific T
      cell clones from two MG thymomas. They recognize extracellular epitopes (alpha75
      90 and alpha149-158) which are processed very efficiently from muscle AChR. Both
      clones express CD4 and CD8alpha, and have a Th-0 cytokine profile, producing IL-4
      as well as IFN-gamma. They are restricted to HLA-DP14 and DR52a; expression of
      these minority isotypes was strong on professional antigen-presenting cells in
      the donors' tumors, although it is generally weak in the periphery. The two
      clones' T cell receptor beta chains are different, but their alpha chain
      sequences are very similar. These resemblances, and the striking contrasts with T
      cells previously cloned from non-thymoma patients, show that thymomas generate
      and actively induce specific T cells rather than merely failing to tolerize them
      against self antigens.

PMID- 9593784
TI  - The PML/RARalpha fusion protein inhibits tumor necrosis factor-alpha-induced
      apoptosis in U937 cells and acute promyelocytic leukemia blasts.
AB  - We investigated the effect of the acute promyelocytic leukemia (APL) specific
      PML/RARalpha fusion protein on the sensitivity to TNF-alpha-mediated apoptosis.
      The U937 leukemia cell line was transduced with PML/RARalpha cDNA. PML/RARalpha
      expression caused a markedly reduced sensitivity to TNF-alpha, even if apoptosis
      was triggered by agonistic antibodies to TNF-alpha receptors I and II (TNF
      alphaRI, II). PML/RARalpha induced a 10-20-fold decrease of the TNF-alpha-binding
      capacity via downmodulation of both TNF-alphaRI and TNF-alphaRII: this may
      mediate at least in part the reduced sensitivity to TNF-alpha. Furthermore, the
      fusion protein did not modify Fas expression (CD95) or sensitivity to Fas
      mediated apoptosis. The pathophysiological significance of these findings is
      supported by two series of observations. (a) Fresh APL blasts exhibit no TNF
      alpha binding and are resistant to TNF-alpha-mediated apoptosis. Conversely,
      normal myeloblasts-promyelocytes show marked TNF-alphaR expression and are
      moderately sensitive to TNF-alpha-mediated cytotoxicity. Similarly, blasts from
      other types of acute myeloid leukemia (AML M1, M2, and M4 FAB types) show an
      elevated TNF-alpha binding. (b) The NB4 APL cell line, which is PML/RARalpha+,
      shows low TNF-alphaR expression capacity and is resistant to TNF-alpha-triggered
      apoptosis; conversely a PML/RARalpha- NB4 subclone (NB4.306) exhibits detectable
      TNF-alpha-binding capacity and is sensitive to TNF-alpha-mediated cytotoxicity.
      These studies indicate that the PML/RARalpha fusion protein protects against TNF
      alpha-induced apoptosis, at least in part via downmodulation of TNF-alphaRI/II:
      this phenomenon may play a significant role in APL, which is characterized by
      prolonged survival of leukemic blasts.

PMID- 9593785
TI  - Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients
      with chronic myelogenous leukemia.
AB  - Human chronic myelogenous leukemia (CML) is characterized by a translocation
      between chromosomes 9 and 22 that results in a BCR-ABL fusion gene coding for
      chimeric proteins. The junctional region of the BCR-ABLb3a2 molecule represents a
      potential leukemia-specific antigen which could be recognized by cytotoxic T
      lymphocytes (CTL). In fact, we identified a junctional nonapeptide (SSKALQRPV)
      which binds to HLA-A2.1 molecules. This peptide, as well as those binding to HLA
      A3, -A11, and -B8 molecules (previously identified by others), elicits primary
      CTL responses in vitro from PBLs of both healthy donors and CML patients. Such
      CTL recognize HLA-matched, BCR-ABL-positive leukemic cells, implying efficient
      natural processing and presentation of these junctional peptides. Specific CTL
      were found at high frequency in 5 of 21 CML patients, suggesting that these
      epitopes are, to some extent, immunogenic in vivo during the course of the
      disease. These peptides could be useful for the development of specific
      immunotherapy in CML patients.

PMID- 9593786
TI  - Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of
      molecular screening for the disease.
AB  - BACKGROUND: Genetic disorders that predispose people to colorectal cancer include
      the polyposis syndromes and hereditary nonpolyposis colorectal cancer. In
      contrast to the polyposis syndromes, hereditary nonpolyposis colorectal cancer
      lacks distinctive clinical features. However, a germ-line mutation of DNA
      mismatch-repair genes is a characteristic molecular feature of the disease. Since
      clinical screening of carriers of such mutations can help prevent cancer, it is
      important to devise strategies applicable to molecular screening for this
      disease. METHODS: We prospectively screened tumor specimens obtained from 509
      consecutive patients with colorectal adenocarcinomas for DNA replication errors,
      which are characteristic of hereditary colorectal cancers. These replication
      errors were detected through microsatellite-marker analyses of tumor DNA. DNA
      from normal tissue from the patients with replication errors was screened for
      germ-line mutations of the mismatch-repair genes MLH1 and MSH2. RESULTS: Among
      the 509 patients, 63 (12 percent) had replication errors. Specimens of normal
      tissue from 10 of these 63 patients had a germ-line mutation of MLH1 or MSH2. Of
      these 10 patients (2 percent of the 509 patients), 9 had a first-degree relative
      with endometrial or colorectal cancer, 7 were under 50 years of age, and 4 had
      had colorectal or endometrial cancer previously. CONCLUSIONS: In this series of
      patients with colorectal cancer in Finland, at least 2 percent had hereditary
      nonpolyposis colorectal cancer. We recommend testing for replication errors in
      all patients with colorectal cancer who meet one or more of the following
      criteria: a family history of colorectal or endometrial cancer, an age of less
      than 50 years, and a history of multiple colorectal or endometrial cancers.
      Patients found to have replication errors should undergo further analysis for
      germ-line mutations in DNA mismatch-repair genes.

PMID- 9593789
TI  - Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group
      on Chronic Lymphocytic Leukemia.
AB  - BACKGROUND: To determine whether chlorambucil treatment benefits patients with
      indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials
      in 1535 patients with previously untreated stage A CLL. METHODS: In the first
      trial, 609 patients were randomly assigned to receive either daily chlorambucil
      or no treatment; in the second trial, 926 patients were randomly assigned to
      receive either intermittent chlorambucil plus prednisone or no treatment. Median
      follow-up for the first and second trials exceeded 11 and 6 years, respectively.
      The end points were overall survival, response to treatment, and disease
      progression. RESULTS: Treatment of indolent CLL did not increase survival in
      either trial. In the treated group, as compared with the untreated group, the
      relative risk of death was 1.14 (95 percent confidence interval, 0.92 to 1.41;
      P=0.23) in the first trial and 0.96 (95 percent confidence interval, 0.75 to
      1.23; P=0.74) in the second trial, with 76 percent and 69 percent of patients,
      respectively, having a response to therapy. Although chlorambucil slowed disease
      progression, there was no effect on overall survival. In the untreated group in
      the first trial, 49 percent of patients did not have progression to more advanced
      disease and did not need therapy after follow-up of more than 11 years; however,
      27 percent of patients with stage A CLL died of causes related to the disease.
      CONCLUSIONS: Chlorambucil does not prolong survival in patients with stage A CLL.
      Since deferring therapy until the disease progresses to stage B or C does not
      compromise survival, treatment of indolent CLL is unnecessary.

PMID- 9593790
TI  - Images in clinical medicine. Volitional and emotional supranuclear facial
      weakness.

PMID- 9593791
TI  - The treatment of unrelated disorders in patients with chronic medical diseases.
AB  - BACKGROUND: Patients can have several illnesses concurrently, yet some of these
      diseases may be neglected if one problem consumes attention. We conducted a
      population-based analysis in Ontario, Canada - where universal health insurance
      is provided - to determine whether unrelated disorders are less likely to be
      treated in patients with chronic diseases. METHODS: We studied the 1,344,145
      residents of Ontario in 1995 who were 65 or older and eligible to receive
      prescription medications free of charge as part of the Ontario Drug Benefit
      program. Patients with diabetes mellitus were identified by prescriptions for
      insulin, pulmonary emphysema by prescriptions for ipratropium bromide, and
      psychotic syndromes by prescriptions for haloperidol. For each chronic disease,
      we selected an unrelated treatment: estrogen-replacement therapy for patients
      with diabetes mellitus, lipid-lowering medications for those with pulmonary
      emphysema, and medical treatment of arthritis for those with psychotic syndromes.
      RESULTS: The 30,669 patients with diabetes mellitus were less likely to receive
      estrogen-replacement therapy than the other subjects in the study (2.4 percent
      vs. 5.9 percent, P<0.001). The disease was associated with a 60 percent reduction
      in the odds of estrogen treatment (odds ratio, 0.40; 95 percent confidence
      interval, 0.37 to 0.43). Findings were similar for the 56,779 patients with
      pulmonary emphysema, who were less likely to receive lipid-lowering medications
      (odds ratio, 0.69; 95 percent confidence interval, 0.67 to 0.72; P<0.001), and
      the 17,336 patients with psychotic syndromes, who were less likely to receive
      medical treatments for arthritis (odds ratio, 0.59; 95 percent confidence
      interval, 0.57 to 0.62; P<0.001). CONCLUSIONS: In patients 65 or older who have
      chronic medical diseases and who receive prescription medications free of charge,
      unrelated disorders are undertreated. Clinicians caring for patients with chronic
      diseases should remain alert to other disorders and minimize the number of missed
      opportunities for treating them.

PMID- 9593792
TI  - Acute diverticulitis.

PMID- 9593794
TI  - Identifying hereditary nonpolyposis colorectal cancer.

PMID- 9593795
TI  - Platelet glycoprotein IIb/IIIa receptor blockade in unstable coronary disease.

PMID- 9593796
TI  - Patients with multiple chronic conditions--how many medications are enough?

PMID- 9593798
TI  - Correlation between local vascular and sensory changes following tissue
      inflammation induced by repetitive application of topical capsaicin.
AB  - The aim of the present study was to investigate local vascular and sensory
      changes and their correlation in order to obtain a better understanding of the
      mechanisms of allodynia, hyperalgesia and vascular changes following tissue
      inflammation induced by repetitive application of capsaicin cream. This type of
      application was utilized as a controlled model of inflammation which was altered
      in intensity due to its repetitive applicability. Ten healthy volunteers
      participated in two experiments separated by at least five days. Each experiment
      consisted of a baseline session followed by five additional sessions. Before
      these sessions either 1.5 g capsaicin (1%) or placebo cream was applied to the
      volar site of the forearm for 15 min. The areas of stroking allodynia and pin
      prick hyperalgesia were mapped and the intensity of spontaneous pain (VAS) was
      assessed after each application of the cream. In addition, the visible flare,
      temperature (IR-Thermography), and blood- flow (Laser-Doppler) were measured. The
      first application of capsaicin was perceived as painful; it induced both
      secondary hyperalgesia and allodynia. Compared to placebo, the first application
      of capsaicin cream also resulted in an increased blood-flow, elevated temperature
      and visible flare. The highest values of these sensory and vascular parameters
      were reached after the third application. A direct correlation between visible
      flare, secondary mechanical hyperalgesia and allodynia following repetitive
      application of capsaicin indicates that both common central and peripheral
      mechanisms were involved in these changes.

PMID- 9593799
TI  - Water-deprived white-footed mice express c-fos on a day/night cycle graded
      according to the duration of deprivation.
AB  - Mammals respond to electrolyte and water imbalance by a variety of neural and
      endocrine mechanisms that regulate water and salt intake and loss. We used the
      expression of c-fos and Fos-related antigens to indicate neuronal activation in
      hypothalamic neurons of members of an outbred laboratory population of white
      footed mice (Peromyscus leucopus) deprived of water for biologically reasonable
      periods of time (6-18 h). We examined Fos-like immunoreactivity (Fos-LIR) in the
      supraoptic nucleus (SON) and paraventricular nucleus (PVN). During the dark
      period, when these animals are normally active, 6 h of water deprivation produced
      near-maximal increases in the number of cells positive for Fos-LIR in the SON and
      PVN. In contrast, during the light period, when these mice are normally inactive
      and do not have access to water, 6 h of water deprivation only slightly affected
      Fos-LIR. During the day, it required as much as 12 h of water deprivation to
      produce increases in Fos-LIR cells approaching those achieved at night. Plasma
      osmolarity was directly related to the number of Fos-LIR cells. In addition, mice
      lost weight more rapidly at night than during the day when water-deprived, and
      also recovered that lost weight more rapidly when access to water was returned.
      Our results show (1) that biologically reasonable levels of water restriction
      (and resulting changes in blood osmolarity) induce changes in Fos-LIR in this
      wild mouse species, and (2) that these mice have a daily cycle of sensitivity to
      water deprivation that is demonstrated by both behavioral, psychological and
      immunohistological assessment of reactions to water deprivation.

PMID- 9593800
TI  - Temporal ordering of pathogenic events following transient global ischemia.
AB  - Rats were subjected to transient global ischemia (four vessel occlusion) and time
      related changes in the selectively vulnerable hippocampal field CA1 were
      characterized. The assessment included ex vivo field responses to afferent
      stimulation, silver staining, calpain-induced spectrin breakdown, chromatolysis,
      and cell death, beginning at 6 h post-ischemia and continuing until total
      disintegration of the pyramidal cells occurred several days later. The earliest
      change observed was a modest increase in the slope and amplitude of field CA1
      potentials (at 6 h). The hyperresponsiveness was most apparent at higher
      stimulation currents and persisted unchanged at 16 h post-ischemia. Three effects
      became detectable within 24 h, post-ischemia: (a) an increase in concentrations
      of calpain-mediated, spectrin breakdown products; (b) enhanced silver staining in
      the deep pyramidal neurons of the field CA1 with lesser, though still apparent,
      staining of stratum radiatum, and (c) a decrease in amplitude and slope of field
      CA1 responses to afferent stimulation. Both the concentration of spectrin
      breakdown products and the intensity of silver staining progressively increased
      to a maximum at four days post ischemia, while the amplitude and slope of the
      field responses dropped to a very low level between 24 and 48 h. Disturbances of
      Nissl staining were finally evident at 48 h, with nearly complete disappearance
      of staining at five days post-ischemia. This study provides the first
      demonstration of a close and early temporal relationship between calpain
      proteolysis, subcellular damage to the pyramidal cells and their loss of function
      following global ischemia, prior to their eventual death.

PMID- 9593801
TI  - Apolipoprotein-mediated cellular cholesterol efflux.

PMID- 9593802
TI  - Intracarotid low dose bradykinin infusion selectively increases tumor
      permeability through activation of bradykinin B2 receptors in malignant gliomas.
AB  - Intracarotid low dose bradykinin infusion can selectively increase permeability
      in brain tumor capillaries. However, the mechanism by which bradykinin
      selectively increases transport into brain tumors and not normal brain has not
      been clearly defined. This study therefore sought to determine whether the
      mechanism by which bradykinin increases tumor permeability specifically involves
      the bradykinin B2 receptor in brain tumor tissue. In permeability studies, 27
      Wistar rats with RG2 gliomas were utilized and a unidirectional transport, Ki, of
      radiolabeled [14C] sucrose was determined using quantitative autoradiography.
      Bradykinin (10 microg kg-1 min-1) increased the transport of sucrose to tumors
      2.1-fold compared to saline infusion alone (p<0.001). The uptake of sucrose in
      tumors was significantly inhibited by the bradykinin B2 receptor antagonist, d
      Arg, [Hyp3, Thi5,8, d-Phe7]-bradykinin (p<0.01), but not by the B1 receptor
      antagonist, des-Arg9, [Leu8]-bradykinin. The distribution of B2 receptors in
      normal brain and tumor tissue was examined by immunohistochemistry using the B2
      receptor antiserum, AS 424. High levels of B2 receptors were detected in
      intracerebral RG2 glioma and brain surrounding tumor (BST), but not in normal
      brain tissue. These results indicate that the permeabilizing effects of
      bradykinin are mediated through bradykinin B2 receptors, and that differences in
      distribution of B2 receptors between tumor tissue and normal brain may be
      responsible for the selective effects on tumor tissue.

PMID- 9593803
TI  - Distribution of advanced glycation end products in the cerebellar neurons of
      dogs.
AB  - Nonenzymatically glycated proteins and their advanced stage, the 'advanced
      glycation end products' (AGEs), have been detected in long-lived proteins and
      protein deposits in human and animal tissues. They are thought to be associated
      with normal aging and particularly with the pathogenesis of diabetic
      complications and Alzheimer's disease. AGEs accumulate in human neurons in an age
      dependent manner and, in Alzheimer's disease patients, particularly in amyloid
      plaques and neurofibrillary tangles. In this study, we demonstrate AGE
      immunoreactivity in the canine brain, particularly in cerebellar Purkinje cells
      and brainstem neurons. In addition, distinct AGE-positive granules can be
      detected in the Purkinje cells which accumulate in an age-dependent manner.
      Staining with PAS and oil-red suggests that these AGE-positive granules contain
      the protein, but not the lipid constituents associated with lipofuscin. Our
      results show that the pattern of AGE distribution in the canine cerebellum
      resembles the situation in the human brain, but that the time course of AGE
      formation is much faster in dogs reflecting their much shorter life span.

PMID- 9593805
TI  - Improvement of ischemic damage in gerbil hippocampal neurons by procaine.
AB  - Acute cerebral ischemia induces membrane depolarization in the neuron, thereby
      incurring the simultaneous influx of various ions such as Na+ and Ca2+. Since
      procaine possesses the ability to inhibit the release of Ca2+ from intracellular
      Ca2+ stores to the cytosol as well as the ability to block Na+ channels, the
      effects of procaine on ischemia were investigated in the present study in gerbils
      both in vivo and in vitro. The histologic outcome was evaluated 7 days after 3
      min of transient forebrain ischemia by assessing delayed neuronal death in
      hippocampal CA1 pyramidal cells in animals administered procaine (0.2, 0.4, or 2
      micromol) intracerebroventricularly 10 min before ischemia and in animals given
      saline. The changes in the direct-current potential shift in the hippocampal CA1
      area were measured using an identical animal model. A hypoxia-induced
      intracellular Ca2+ increase was evaluated by in vitro microfluorometry in gerbil
      hippocampal slices, and the effects of procaine (10, 50, and 100 micromol/l) on
      the Ca2+ accumulation were examined. Additionally, the effect of procaine (100
      micromol/l) in a Ca2+-free condition was investigated. The histologic outcome was
      improved and the onset of the ischemia-induced membrane depolarization was
      prolonged by the preischemic administration of procaine. The increase in the
      intracellular concentration of Ca2+ induced by the in vitro hypoxia was
      suppressed by the perfusion of procaine-containing mediums (50 and 100
      micromol/l), regarding both the initiation and the extent of the increase. A
      hypoxia-induced intracellular Ca2+ elevation in the Ca2+-free condition was
      observed, and the perfusion with procaine (100 micromol/l) inhibited this
      elevation. Procaine helps protect neurons from ischemia by suppressing the direct
      current potential shift and by inhibiting the release of Ca2+ from the
      intracellular Ca2+ stores, as well as by inhibiting the influx of Ca2+ from the
      extracellular space.

PMID- 9593806
TI  - Continuous spectrophotometric assay of mammalian phosphoinositide-specific
      phospholipase Cdelta1 with a thiophosphate substrate analog.
AB  - 1,2-Dimyristoyloxypropane-3-thiophospho(1D-1-myo-inositol) (D-thio-DMPI) was used
      as a substrate for the continuous assay of phosphoinositide-specific
      phospholipase C (PI-PLC). Its activity with a Delta(1-132) deletion mutant of
      mammalian PI-PLCdelta1 is about one-fourth that with PI under similar conditions.
      Optimal conditions for the assay include 0.2 mM substrate, 0.2 mM Ca2+, and a
      mole ratio of hexadecylphosphocholine detergent to substrate of 2.0. A minimum of
      about 60 ng of pure enzyme can be detected. The apparent bulk Km for PI-PLC with
      D-thio-DMPI under these conditions is about 6 microM. Enzyme activity as a
      function of surface concentration of substrate shows no sign of saturation up to
      the maximum mole fraction.

PMID- 9593804
TI  - Antinociception produced by microinjection of morphine in the rat periaqueductal
      gray is enhanced in the foot, but not the tail, by intrathecal injection of
      alpha1-adrenoceptor antagonists.
AB  - Antinociception produced by microinjection of morphine in the ventrolateral
      periaqueductal gray is mediated in part by alpha2-adrenoceptors in the spinal
      cord dorsal horn. However, several recent reports demonstrate that microinjection
      of morphine in the ventrolateral periaqueductal gray inhibits nociceptive
      responses to noxious heating of the tail by activating descending neuronal
      systems that are different from those that inhibit the nociceptive responses to
      noxious heating of the feet. More specifically, alpha2-adrenoceptors appear to
      mediate the antinociception produced by morphine using the tail-flick test, but
      not that using the foot-withdrawal or hot-plate tests. The present study extended
      these findings and determined the role of alpha1-adrenoceptors in mediating the
      antinociceptive effects of morphine microinjected into the ventrolateral
      periaqueductal gray using both the foot-withdrawal and the tail-flick responses
      to noxious radiant heating in lightly anesthetized rats. Intrathecal injection of
      selective antagonists was used to determine whether the antinociceptive effects
      of morphine were modulated by alpha1-adrenoceptors. Injection of the selective
      alpha1-adrenoceptor antagonists prazosin or WB4101 potentiated the increase in
      the foot-withdrawal response latency produced by microinjection of morphine in
      the ventrolateral periaqueductal gray. In contrast, either prazosin or WB4101
      partially reversed the increase in the tail-flick response latency produced by
      morphine. These results indicate that microinjection of morphine in the
      ventrolateral periaqueductal gray modulates nociceptive responses to noxious
      heating of the feet by activating descending neuronal systems that are different
      from those that inhibit the nociceptive responses to noxious heating of the tail.
      More specifically, alpha1-adrenoceptors mediate a pro-nociceptive action of
      morphine using the foot-withdrawal response, but in contrast, alpha1
      adrenoceptors appear to mediate part of the antinociceptive effect of morphine
      determined using the tail-flick test.

PMID- 9593807
TI  - Effects of the self-administration of ethanol and ethanol/sucrose on rates of
      local cerebral glucose utilization in rats.
AB  - In a previous study, the voluntary ingestion of ethanol by rats was found to be
      associated with a discrete pattern of changes in functional activity that
      included the nucleus accumbens, medial prefrontal cortex, basolateral and central
      nuclei of the amygdala, as well as the ventral midbrain. Rats in this study,
      however, consumed a combination of ethanol in a sucrose vehicle. The purpose of
      the present experiment was to characterize the role of sucrose in determining the
      effects of orally self-administered ethanol using the quantitative
      autoradiographic 2-[14C]deoxyglucose (2DG) method for measurement of rates of
      local cerebral glucose utilization. A modified sucrose-substitution procedure was
      employed to train three groups of Wistar rats to self-administer either water,
      10% ethanol (10E), or a 10% ethanol/2% sucrose solution (10E/2S) in daily
      sessions. An additional group of rats was trained using a modified acclimation
      procedure (home cage) in order to determine if any exposure to sucrose would
      alter rates of glucose utilization. Once stable rates of consumption were
      established, the 2DG method was applied immediately following completion of the
      final test session. Rats received a dose of ethanol equivalent to 0.5 g kg-1 on
      the day of the procedure or a comparable volume of water. Rates of energy
      metabolism were significantly increased in all three groups of rats that consumed
      ethanol (10E/2S, 10E, and home cage), as compared to rates in rats that consumed
      water. The areas of significant change included the rostral pole and posterior
      shell of the nucleus accumbens, medial prefrontal cortex, the basolateral and
      central nuclei of the amygdala, the ventral tegmental area, and the substantia
      nigra pars compacta. Thus, the pattern of changes in functional brain activity
      that accompanies voluntary ingestion of ethanol is independent of the vehicle in
      which the ethanol is presented or the procedures used to initiate consumption.
      Furthermore, these data demonstrate that it is the simultaneous activation of an
      interrelated network of limbic brain regions that serves as the substrate of the
      effects of ethanol self-administration.

PMID- 9593808
TI  - Strong dependence of the lipid peroxidation product spectrum whether Fe2+/O2 or
      Fe3+/O2 is used as oxidant.
AB  - Catalytic amounts of Fe2+ or Fe3+ ions are widely applied to induce simulated
      biological lipid peroxidation reactions. Independently, whether Fe2+ or Fe3+ were
      used, similar products were obtained. We show in this paper that the product
      spectrum is indeed very different, whether one ion species, either Fe2+ or Fe3+,
      is present in excess; thus, decomposition of (13S,9Z,11E) 13-hydroxyperoxy-9, 11
      octadecadienoic acid (13S-HPODE) generates in the presence of equimolar amounts
      of Fe2+ ions mainly the corresponding alcohol (13S, 9Z,11E) 13-hydroxy-9,11
      octadecadienoic acid besides 12,13-epoxy-11-hydroxy-9-octadecenoic acid (12,13
      epHOD) and 13-oxo-9,11-octa-decadienoic acid (13-KODE), while decomposition of
      13S-HPODE with equimolar amounts of Fe3+ produces mainly 12,13-epHOD, hydrolysis
      products thereof and other oxidized products, e.g., hydroxyoxo acids. In
      addition, unusually large amounts of aldehydes are formed, e.g., the amount of 4
      hydroxy-nonenal was found to exceed that obtained by Fe2+ induced air oxidation
      for a factor of about 100. Since these further oxidation products are suspected
      to cause cell damage, liberated Fe3+ ions seem to be responsible for generation
      of toxic products in inflammatory diseases, e.g., atherosclerosis.

PMID- 9593809
TI  - Nonlinear interdependencies of EEG signals in human intracranially recorded
      temporal lobe seizures.
AB  - The degree of interdependence between intracranial EEG channels was investigated
      in four epileptic patients with complex partial seizures of mesial temporal lobe
      origin. With a new method to characterize nonlinear dynamical interdependence-the
      mutual nonlinear prediction-we demonstrated here a possibility to quantify,
      during epileptic seizures, the relationships between EEG signals of electrode
      contacts in the epileptogenic area. During the interictal period, the degree of
      nonlinear interdependences were very low or absent. In contrast, it was found
      that transient patterns of nonlinear interdependences emerge at the initial
      spread of the seizure, during essential parts of its development, and at seizure
      end, but the maintenance of these interactions are not observed throughout the
      seizure activity. These results suggest that the nonlinear associations plays an
      important role in epileptogenesis, and that the process of neuronal entrainment
      during seizure onset involves a transient interaction between a distributed
      network of neuronal aggregates, but the maintenance of this interaction is not
      required for sustained seizure activity. Furthermore, this technique can describe
      properly the spatio-temporal organisation of the seizures of medio-temporal lobe
      origin and could become a very useful tool to aid the localization of the
      epileptogenic regions at the origin of epileptic seizures and their pathways of
      propagation.

PMID- 9593810
TI  - Hypovolemia upregulates the expression of neuronal nitric oxide synthase gene in
      the paraventricular and supraoptic nuclei of rats.
AB  - We have examined the effects of isotonic hypovolemia on the expression of the
      neuronal nitric oxide synthase (nNOS) gene in the paraventricular (PVN) and
      supraoptic nuclei (SON) of the rat, using in situ hybridization histochemistry
      with a 35S-labelled oligodeoxynucleotide probe complementary to nNOS mRNA.
      Intraperitoneal (i.p.) administration of polyethylene glycol (PEG) (MW 4000, 20
      ml/kg body weight) dissolved in 0.9% saline (20% w/v) induced isotonic
      hypovolemia. The expression of the nNOS gene in the PVN and SON 6 h after i.p.
      administration of PEG was increased significantly in comparison with controls.
      The dual staining for NADPH diaphorase activity and Fos-like immunoreactivity
      (Fos-LI) showed that at 3 and 6 h after i.p. administration of PEG, a
      subpopulation of NADPH diaphorase-positive cells in the PVN and SON exhibited
      nuclear Fos-LI. These results suggest that NO in the PVN and SON may be involved
      in the neuroendocrine and autonomic responses to non-osmotic hypovolemia.

PMID- 9593811
TI  - The expression of Fos within the suprachiasmatic nucleus of the diurnal rodent
      Arvicanthis niloticus.
AB  - Rhythms in the expression of the nuclear phosphoprotein Fos, have been
      demonstrated in the suprachiasmatic nucleus (SCN) of nocturnal rodents. When rats
      are housed in a 12:12-h light/dark (LD) cycle the number of Fos-immunoreactive (
      IR) cells within the SCN is higher during the day than at night [9,23]. In the
      two experiments reported here, Fos-IR was examined in the SCN of a diurnal murid
      rodent, Arvicanthis niloticus. First, thirty-six adult male A. niloticus housed
      in a 12:12-h LD cycle were perfused at six equally spaced time points beginning 1
      h after lights on (n=6 per time point). Brains were sectioned and treated with
      immunohistochemical procedures for the identification of Fos. The number of Fos
      IR cells in the SCN varied significantly as a function of time, and was highest 1
      h after lights on and decreased thereafter. The distribution of Fos-IR within the
      SCN overlapped with that of arginine-vasopressin-IR (AVP-IR) and vasoactive
      intestinal peptide-IR (VIP-IR), but not with that of gastrin-releasing peptide-IR
      (GRP-IR). In the second study, double-labeling techniques revealed extensive Fos
      expression within SCN neurons containing AVP-IR, but not neurons containing GRP
      IR. In conclusion, although the overall rhythm of Fos-IR in the SCN is similar in
      diurnal and nocturnal rodents, differences may exist with respect to the relative
      distribution of Fos-immunoreacte cells within different SCN cell populations.

PMID- 9593812
TI  - Phasic activation of the locus coeruleus enhances responses of primary sensory
      cortical neurons to peripheral receptive field stimulation.
AB  - In the present study we examined the effects of phasic activation of the nucleus
      locus coeruleus (LC) on transmission of somatosensory information to the rat
      cerebral cortex. The rationale for this investigation was based on earlier
      findings that local microiontophoretic application of the putative LC
      transmitter, norepinephrine (NE), had facilitating actions on cortical neuronal
      responses to excitatory and inhibitory synaptic stimuli and more recent
      microdialysis experiments that have demonstrated increases in cortical levels of
      NE following phasic or tonic activation of LC. Glass micropipets were used to
      record the extracellular activity of single neurons in the somatosensory cortex
      of halothane-anesthetized rats. Somatosensory afferent pathways were activated by
      threshold level mechanical stimulation of the glabrous skin on the contralateral
      forepaw. Poststimulus time histograms were used to quantitate cortical neuronal
      responses before and at various time intervals after preconditioning burst
      activation of the ipsilateral LC. Excitatory and postexcitatory inhibitory
      responses to forepaw stimulation were enhanced when preceded by phasic activation
      of LC at conditioning intervals of 200-500 ms. These effects were anatomically
      specific in that they were only observed upon stimulation of brainstem sites
      close to (>150 micron) or within LC and were pharmacologically specific in that
      they were not consistently observed in animals where the LC-NE system had been
      disrupted by 6-OHDA pretreatment. Overall, these data suggest that following
      phasic activation of the LC efferent system, the efficacy of signal transmission
      through sensory networks in mammalian brain is enhanced.

PMID- 9593813
TI  - Immunocytochemical analysis of sex differences in calcitonin gene-related peptide
      in the rat dorsal root ganglion, with special reference to estrogen and its
      receptor.
AB  - Previous studies have shown that the calcitonin gene-related peptide (CGRP)
      immunoreactivity in the central nervous system (CNS) of adult rats is sexually
      dimorphic and regulated by sex steroid. In the present study, we used
      immunocytochemistry to investigate the sex difference in CGRP-immunoreactive (IR)
      neurons in rat dorsal root ganglia (DRG). The numbers of CGRP-IR neurons at the
      cervical, lumbar and sacral levels in the female rats were significantly lower
      than those of the male rats. We also found that the number of CGRP-IR neurons at
      the lumbar level was increased in ovariectomized (OVX) rats, but was decreased in
      estradiol (E2)-treated rats (OVX+E2). A large number of estrogen receptor (ER)-IR
      neurons at the lumbar level were found in the female rats, and its number was
      greater than that in the male rats. We also investigated the change in the number
      of ER-IR neurons of OVX rats after estrogen treatment. The number of ER-IR
      neurons in the OVX+E2 rats was consistent with that of the intact female rats,
      but was significantly increased in the OVX rats. As shown by a double-labeling
      immunocytochemical method, over 80% of the CGRP-IR neurons at the lumbar level
      showed ER immunoreactivity in the female, OVX and OVX+E2 rats, compared to only
      about 46% in the male rats. These results indicate that there is a gender
      difference in CGRP expression in the rat DRG, and that this CGRP expression might
      be downregulated by estrogen (at least in part) through its receptor.

PMID- 9593814
TI  - Taurine-activated chloride currents in the rat sacral dorsal commissural neurons.
AB  - The electrophysiological and pharmacological properties of taurine (Tau)
      activated Cl- currents (ITau) were investigated in the dissociated rat sacral
      dorsal commissural nucleus (SDCN) neurons using the nystatin perforated patch
      recording configuration under voltage-clamp conditions. The reversal potential of
      ITau was close to the Cl- equilibrium potential. The ITau was not affected by a
      preceding GABA response but cross-desensitized by a preceding glycine (Gly)
      response. Strychnine (STR), picrotoxin (PIC), bicuculline (BIC) and Zn2+
      suppressed the ITau in a concentration-dependent manner. The pharmacology of the
      ITau and Gly-induced response (IGly) was similar, though Zn2+ inhibition on ITau
      differed from that on IGly in being much slower in recovery. Serotonin
      potentiated the ITau via protein kinase C. The results indicate that both Tau and
      Gly act on a strychnine-sensitive site to open the same Cl- channels in the SDCN
      neurons, and suggest that Tau may act as a functional neurotransmitter in the
      mammalian SDCN.

PMID- 9593815
TI  - Hypocholesterolemic properties of nitric oxide. In vivo and in vitro studies
      using nitric oxide donors.
AB  - Previous results suggested that changes in the activity of nitric oxide (NO) can
      influence metabolism of apo B-containing lipoproteins. Therefore, we studied
      effects of exogenous NO donors and physiological NO precursors on metabolism of
      these lipoproteins. In rabbits, addition of 0.03% sodium nitroprusside (NaNP) to
      a semipurified, cholesterol-free, casein diet counteracted the elevation of LDL
      cholesterol induced by this diet but did not alter liver lipids after 4 weeks of
      feeding. In HepG2 cells, addition of nontoxic concentrations of another NO donor,
      S-nitroso-N-acetylpenicillamine (SNAP) to culture medium caused a dose-dependent
      reduction of medium apo B after 24 h. At the concentration 0.5 mM, SNAP
      significantly decreased medium apo B by 50% without altering total synthesis and
      secretion of proteins and without altering rates of cellular sterol synthesis. In
      cells incubated with L-arginine, reduction of medium apo B was not associated
      with increased NO production whereas in those exposed to N-OH-Arg medium apo B
      levels were not altered. We concluded that synthetic NO donors can reduce
      hypercholesterolemia by affecting apo B metabolism directly in the liver, via the
      sterol-independent mechanism.

PMID- 9593816
TI  - Differential roles of two types of voltage-gated Ca2+ channels in the dendrites
      of rat cerebellar Purkinje neurons.
AB  - The distribution and function of voltage-gated Ca2+ channels in Purkinje neurons
      in rat cerebellar slices were studied using simultaneous Ca2+ imaging and whole
      cell patch clamp recording techniques. Voltage-gated Ca2+ channels were activated
      by applying depolarizing voltage steps through the pipette attached at the soma
      in a voltage-clamp mode in the presence of tetrodotoxin. Poor space clamp due to
      extensive arborization of the dendrites allowed the dendrites to fire Ca2+
      spikes. Ca2+ imaging with Fura-2 injected through the pipette, showed a steady
      [Ca2+]i increase at the soma and transient, spike-linked [Ca2+]i jumps in the
      dendrites. omega-Agatoxin-IVA (200 nM) abolished the depolarization-induced Ca2+
      spikes, the spike-linked [Ca2+]i increase in the dendrites, and the steady
      [Ca2+]i increase at the soma. omega-Conotoxin-GVIA (5 microM) and nifedipine (3
      microM) had no significant effect on the depolarization-induced responses. In the
      presence of 4-aminopyridine(2 mM) and omega-Agatoxin-IVA, transient [Ca2+]i
      increases remained in the dendrites. Low concentrations of Ni2+(100 microM)
      reversibly suppressed this [Ca2+]i increase. The voltage for half-maximal
      activation and inactivation of this component were lower than -50 mV and -31 mV,
      respectively. In normal conditions, low concentration of Ni2+ slowed the onset of
      the Ca2+ spike without changing the time course of the spikes or the amplitude of
      the accompanying [Ca2+]i increase. These results show that omega-Agatoxin-IVA
      sensitive Ca2+ channels are distributed both in the soma and the dendrites, and
      are responsible for dendritic Ca2+ spikes, whereas low-voltage activated, Ni2+
      sensitive Ca2+ channels are distributed in the whole dendrites including both
      thick and fine branches, and provide boosting current for spike generation.

PMID- 9593817
TI  - Occurrence of a N-terminal proteolytic fragment of neurocan, not a C-terminal
      half, in a perineuronal net in the adult rat cerebrum.
AB  - Neurocan is a nervous tissue-unique chondroitin sulfate proteoglycan (CSPG) whose
      expression and proteolytic cleavage are developmentally regulated. In the adult
      rat brain, neurocan is completely cleaved into some proteoglycan fragments
      including the C-terminal half known as neurocan-C and a N-terminal fragment with
      a 130 kDa core glycoprotein (neurocan-130). We describe here the differential
      distribution of these two neurocan-derived CSPGs in the adult rat cerebrum and
      the occurrence of neurocan-130 as a new member of a perineuronal net-constituting
      molecule. At the light microscopic level, neurocan-130 exhibited pericellular
      localization around a subset of neurons in addition to diffuse distribution in
      the neuropil. In contrast, neurocan-C was distributed only diffusely in the
      neuropil. Double staining with anti-neurocan-130 and anti-synaptophysin
      antibodies suggested that neurocan-130 was localized in the vicinity of the
      synapses, but not at the synapses. Immunoelectron microscopy showed that neurocan
      130 was mainly localized in the cytoplasm of glial cell processes, the so-called
      glial perineuronal net, encompassing the cell bodies of certain neurons. The
      presence of neurocan-130 in a limited number of glial cells may reflect some
      functional heterogeneity of the glia.

PMID- 9593818
TI  - Sustained pharmacological inhibition of nitric oxide synthase does not affect the
      survival of intrastriatal rat fetal mesencephalic transplants.
AB  - The objective of the present study was to investigate the potential role of the
      free radical nitric oxide (NO) in the development of fetal rat mesencephalic
      neurons grafted in a 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's
      disease. First, using nitric oxide synthase (NOS)-immunocytochemistry and reduced
      nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry,
      we investigated the presence of the neuronal isoform of NOS (nNOS) in
      intrastriatal mesencephalic grafts. During the course of the experiment (16
      weeks) an increase in the staining intensity and the number of nNOS/NADPH-d
      positive cells within the grafts was observed, as well as a gradual maturation of
      dopaminergic neurons. In addition, within both the host striatal and grafted
      mesencephalic tissue, a NO-dependent accumulation of cyclic guanosine
      monophosphate (cGMP) was detected, indicating the presence of guanylate cyclase,
      i.e., the target-enzyme for NO. Secondly, to determine the impact of NO on the
      survival of grafted dopaminergic neurons, 6-OHDA lesioned rats received
      mesencephalic grafts and were subsequently treated with the competitive NOS
      inhibitor Nomega-nitro-l-arginine methylester (l-NAME). After chronic treatment
      for 4 weeks, tyrosine hydroxylase immunocytochemistry revealed no apparent
      differences between the survival of grafted dopaminergic neurons in control- or l
      NAME treated animals, respectively. As the maturation of grafted dopaminergic
      neurons coincides with a gradual increase in the expression of nNOS within the
      graft and since dopaminergic cell numbers are not changed upon administration of
      l-NAME, it is concluded that endogenously produced and potentially toxic NO does
      not affect the survival of grafted fetal dopaminergic neurons.

PMID- 9593819
TI  - Expression of an active phytoene synthase from Erwinia uredovora and biochemical
      properties of the enzyme.
AB  - The crtB gene encoding phytoene synthase from the carotenogenic enterobacterium
      Erwinia uredovora was overexpressed to about 20% of the total cellular protein in
      Escherichia coli. Formation of the active phytoene synthase had the effect of
      suppressing the growth of the expressing strain. Presumably inhibition of growth
      arose from the depletion of the substrate geranylgeranyl pyrophosphate (GGPP)
      which, in E. coli, is necessary for the synthesis of essential
      prenylpyrophosphate derivatives. In order to overcome the poor growth
      characteristics of the phytoene synthase expressing strain, GGPP levels were
      increased by co-expressing the isoprenoid biosynthetic genes crtE and idi,
      encoding the Erwinia GGPP synthase and Rhodobacter isopentenyl pyrophosphate
      isomerase, respectively. The crude enzyme preparation was partially purified 15
      fold by chromatography on a DEAE column. A non-radioactive assay was developed
      that enabled the conversion of GGPP to phytoene. The reaction product was
      identified by co-chromatography with authentic standards on HPLC systems and
      comparison of spectral characteristics. The phytoene formed in vitro was present
      in both a 15-cis and all-trans isomeric configuration. The essential cofactors
      required were ATP in combinations with either Mn2+ or Mg2+. The Km value for GGPP
      was determined as 41 microM. Phytoene synthesis was inhibited by phosphate ions
      and squalestatin. The I50 value for the latter inhibitor was 15 microM.
      Lineweaver-Burk plots showed constant Km values in the presence or absence of
      squalestatin.

PMID- 9593820
TI  - Kainic acid increases the proliferation of granule cell progenitors in the
      dentate gyrus of the adult rat.
AB  - Granule cell progenitors in the dentate gyrus of the hippocampal formation have
      the unusual capacity to be able to divide in the brains of adult rats and
      primates. The basal proliferation rate of granule cell progenitors in the adult
      rat is low compared with development, however, it is possible that this rate may
      become significantly altered under pathological conditions such as epilepsy. We
      have investigated whether the proliferation of granule cell progenitors is
      increased in adult rats in a model of temporal lobe epilepsy, by using systemic
      bromodeoxyuridine injections to label dividing cells. We report here for the
      first time that granule cell neurogenesis is increased bilaterally 1 week after a
      single unilateral intracerebroventricular injection of kainic acid.
      Bromodeoxyuridine labeled neurons increased at least 6-fold on the side
      ipsilateral to the kainic acid injection compared to controls, but significantly,
      were also increased, by at least 3-fold on the side contralateral to the
      injection. The dividing cells in the subgranular zone were identified as neurons
      since they expressed Class III beta tubulin but not glial fibrillary acidic
      protein.

PMID- 9593821
TI  - Glucocorticoids stimulate TRH and c-fos/c-jun gene co-expression in cultured
      hypothalamic neurons.
AB  - To explore whether the protooncogenes, c-fos/c-jun, might be involved in
      regulating the effect of glucocorticoids on thyrotropin-releasing hormone in
      fetal rat diencephalic neurons, their localization and transcriptional activity
      were investigated using double-labeled in situ hybridization, Northern blot and
      nuclear run-on assays. The results showed that TRH mRNA was coexpressed with both
      c-jun and c-fos in the same neurons. Treatment with dexamethasone, a synthetic
      glucocorticoid, at 10(-8) M, enhanced transcriptional activity resulting in an
      increase in both cell number and intensity of all three mRNAs. The existence of c
      fos/c-jun in thyrotropin-releasing hormone neurons and the increased
      transcriptional activity following dexamethasone treatment suggests that these
      protooncogenes could mediate the effect of glucocorticoids on thyrotropin
      releasing hormone gene expression.

PMID- 9593822
TI  - The effect of duration of cerebral ischemia on brain pyruvate dehydrogenase
      activity, energy metabolites, and blood flow during reperfusion in gerbil brain.
AB  - The objective of this study was to determine whether the duration of an ischemic
      insult effects the activity of the mitochondrial enzyme pyruvate dehydrogenase
      (PDH) in relation to the recovery of metabolites and regional cerebral blood flow
      (rCBF) immediately after ischemia and during reperfusion in gerbil cortex.
      Cerebral ischemia was induced, using the bilateral carotid artery occlusion
      method, for 20 or 60 min, followed by reperfusion up to 120 min. Immediately
      after ischemia PDH activity increased threefold regardless of ischemic duration.
      In the 60-min ischemic group, PDH remained activated, the recovery of high energy
      phosphates and the clearance of lactate were poor, and the rCBF was 48% of
      controls after 20-min reperfusion, decreasing gradually to 26% at 120-min
      reperfusion. In the 20-min ischemic group, PDH activity normalized quickly, the
      restoration of energy phosphates was good, there was a quick reduction in lactate
      within the first 60 min of reperfusion, and the rCBF was 65% of control at 20-min
      reperfusion, and remained over 48% of control throughout reperfusion. Recovery of
      metabolism after reperfusion did not parallel the changes in rCBF in either
      group, most noticeably in the 60-min ischemic group. The slow normalization of
      PDH activity reflected the poor recovery of metabolites in the 60-min ischemic
      group, indicating that PDH activity is important in the resynthesis of energy
      metabolites during reperfusion. In conclusion, prolonging the ischemic insult
      effected PDH activity during reperfusion, impaired recovery of energy
      metabolites, and worsened the recovery of rCBF.

PMID- 9593823
TI  - A comparative study of the metabolism of n-9, n-6 and n-3 fatty acids in
      testicular cells from immature rat.
AB  - Dietary 18 and 20-carbon fatty acids of the n-6 and the n-3 families are
      metabolized to 22:5,n-6 and 22:6,n-3 by a sequence of specific desaturases and
      chain elongation via 24-carbon intermediates. This pathway is regulated so that
      more 22:6,n-3 than 22:5,n-6 is found in the tissues. Rat testis is an exception
      since 22:5,n-6 is present in large proportions in this organ. Therefore rat
      testis appears to be interesting for studies of the detailed synthesis of 22:5,n
      6 compared with that of 22:6,n-3. By using fresh preparations of rat testicular
      cells from 19-day-old rats enriched in Sertoli cells, we compared the metabolism
      of 1-14C-labelled n-3, n-6 and n-9 fatty acids. The testicular cells actively
      synthesized 22:6,n-3 and 22:5, n-6, but not 22:4,n-9 from the 18 and 20-carbon
      precursors. Of 200 mol 14C-labelled C18 and C20 fatty acids added initially,
      approximately 20-40 mol were found as 24-carbon intermediates after 24 h of
      incubation. This indicates that the balanced capacity of elongation, desaturation
      and chain shortening favours the accumulation of 24-carbon intermediates in these
      cells. One exception was [1-14C]20:3,n-9 which was efficiently elongated to
      22:3,n-9 but not to C24 fatty acids. Our data suggests that the poor elongation
      of n-9 fatty acids from C22- to C24 may be an important hindrance in the
      synthesis of 22:4,n-9. The efficient synthesis of 22:5,n-6 may also partly
      explain why this is the major 22-carbon fatty acid in rat testis.

PMID- 9593824
TI  - Drug conditioning induced by intrastriatal apomorphine administration.
AB  - The present study examined (1) whether the neostriatum is involved in a drug
      induced conditioned locomotor response and; (2) whether this structure
      participates in the development of behavioral sensitization. Moreover, the
      present study addressed the question whether the development of behavioral
      sensitization is necessary for the induction of conditioning. Rats received
      injections of either apomorphine (2 microg) or vehicle (solution of 0.1%
      ascorbate/saline) into the dorsal neostriatum daily for 7 days. These treatments
      were performed immediately prior to (apomorphine-paired group and vehicle group)
      or 30 min following (apomorphine-unpaired group) 10-min placement in an open
      field which served as the test environment. After a 3-day drug withdrawal period,
      the animals were given a 10-min non-drug vehicle test trial in the test
      environment. Three days later, a drug test with apomorphine was administered to
      the animals of the paired and unpaired treatment groups; the vehicle group again
      received an injection of vehicle. The analysis of locomotor activity in the open
      field (measured as the distance traversed) revealed that locomotor activity in
      the apomorphine-paired group was higher than in the other groups. There were no
      indications for behavioral sensitization to intrastriatal apomorphine, since the
      locomotor response in the apomorphine-paired group did not increase, but rather
      decreased with daily repeated injections of apomorphine. Furthermore, only the
      apomorphine-paired animals showed a higher locomotor response when tested after
      an intrastriatal injection of vehicle in the previously apomorphine-paired
      environment, which is indicative of a conditioned drug effect. These results
      suggest that the neostriatum is directly involved in the development of drug
      induced conditioning of locomotor behavior but not in the establishment of
      behavioral sensitization.

PMID- 9593825
TI  - Cerebrovascular muscle atrophy is a feature of Alzheimer's disease.
AB  - We examined vascular amyloid-beta deposition and other abnormalities in the
      posterior cerebral artery of consecutive cases of Alzheimer's disease (AD)
      compared to controls. Smooth muscle atrophy was a consistent feature in the cases
      of AD examined (p<0.01) and was surprisingly independent of adjacent amyloid-beta
      deposition. These findings suggest that vascular abnormalities are a consistent
      feature in AD and may be an important contributor to the pathogenesis and
      complications of AD.

PMID- 9593826
TI  - Role of nitric oxide in the regulation of gonadotropin-releasing hormone and
      tyrosine hydroxylase gene expression in the male rat brain.
AB  - It has been recently demonstrated that nitric oxide (NO), a free radical gas
      which may act as neurotransmitter in the brain, can stimulate the in vivo release
      of luteinizing hormone as well as the in vitro hypothalamic release of
      gonadotropin-releasing hormone (GnRH). In order to study the influence of NO on
      GnRH mRNA expression, two inhibitors of NO synthase (NOS) NG-monomethyl-l
      arginine (NMMA) and HP-228, were microinjected into the left lateral ventricle of
      sham-operated and castrated male rats 4 h before sacrifice. Since the
      dopaminergic system can positively influence GnRH gene expression, we have also
      measured in the same animals tyrosine hydroxylase (TH) mRNA in tuberoinfundibular
      dopamine (TIDA) neurons. GnRH and TH mRNA levels were measured at the cellular
      level by quantitative in situ hybridization. The injection of HP-228 or NMMA
      induced a similar decrease (-19.5%) in GnRH mRNA. In castrated animals, the
      hybridization signal was 88% higher than that observed in sham-operated animals.
      Both HP-228 and NMMA produced in castrated animals a 39% decrease in GnRH mRNA.
      In contrast the injection of NOS inhibitors resulted in an increase in the amount
      of TH mRNA in TIDA neurons. The stimulating effect was more striking in HP-228
      treated (+60%) than in NMMA-treated (+32%) animals. Castration did not induce any
      changes in the number of silver grains overlying TIDA neurons, while the
      administration of either HP-228 or NMMA induced a 43% increase in castrated
      animals. These results together with previous ones on GnRH release in vitro
      suggest that NO exerts a positive influence not only on the secretion but also on
      the biosynthesis of GnRH. Since NO appears to play a role in the negative
      regulation of dopamine, it is likely that the increase in GnRH mRNA expression is
      not mediated by the TIDA system.

PMID- 9593827
TI  - The 5-HT1A and 5-HT2A/2C receptor antagonists WAY-100635 and ritanserin do not
      attenuate D-fenfluramine-induced fos expression in the brain.
AB  - D-Fenfluramine is a serotonin (5-hydroxytryptamine, 5-HT) releaser and reuptake
      inhibitor. It is used to study the neurochemical control of feeding and has been
      used to treat obesity. It has also been employed as a pharmacological tool to
      study changes in serotonergic function in psychiatric patients. Brain sites
      activated by D-fenfluramine via the release of 5-HT have been mapped via the
      expression of the immediate early gene c-fos. Studies in our laboratory have
      indicated that D-fenfluramine induces Fos in the hypothalamus and cortex through
      5-HT release. The present study investigated whether 5-HT released by D
      fenfluramine induces Fos expression in the brain by activating 5-HT1A or 5
      HT2A/2C receptors. Rats were pretreated either with WAY-100635, a 5-HT1A
      antagonist, or ritanserin, a 5-HT2A/2C antagonist, prior to d-fenfluramine
      injection. Blockade of either 5-HT1A or 5-HT2A/2C receptors was not sufficient to
      suppress the Fos response to D-fenfluramine in any region of the brain examined,
      including the cingulate cortex, frontal cortex, caudate-putamen, paraventricular
      nucleus of the hypothalamus, amygdala, and brainstem. These results indicate that
      Fos response elicited by D-fenfluramine may be mediated by other receptors, in
      addition to the 5-HT1A or 5-HT2A/2C receptors.

PMID- 9593828
TI  - Neuropeptide Y mRNA and serotonin innervation in the arcuate nucleus of anorexia
      mutant mice.
AB  - The anorexia (anx) mutation causes reduced food intake in preweanling mice,
      resulting in death from starvation within 3-4 weeks. In wild-type rodents,
      starvation induces increased neuropeptide Y (NPY) mRNA levels in the arcuate
      nucleus that promotes compensatory hyperphagia. Despite severely decreased body
      weight and food intake at 3-weeks age, anx/anx mice do not show elevated NPY mRNA
      levels in the hypothalamic arcuate nucleus compared to wild-type/heterozygous
      littermates. The NPY mRNA levels can be upregulated in normal mice at this
      chronological age, because 24-h food deprivation increased arcuate NPY mRNA in
      wild-type littermates. The unresponsiveness of NPY expression in the arcuate of
      anx/anx mice was paralleled by serotonergic hyperinnervation of the arcuate
      nucleus, comparable to the serotonergic hyperinnervation previously reported in
      the rest of the anx/anx brain. This result is consistent with the hypothesis that
      wasting disorders are accompanied by disregulation of NPY mRNA expression in the
      arcuate nucleus, and suggests that reduced food intake, the primary behavioral
      phenotype of the anx/anx mouse, may be the result of altered hypothalamic
      mechanisms that normally regulate feeding.

PMID- 9593829
TI  - The autocrine derivation of the opioid growth factor, [Met5]-enkephalin, in
      ocular surface epithelium.
AB  - Endogenous opioid peptides serve as growth factors in developing, renewing,
      healing, and neoplastic cells and tissues. A native opioid peptide, [Met5]
      enkephalin, termed opioid growth factor (OGF), has been discovered to regulate
      DNA synthesis in the epithelium of the ocular surface. OGF and its receptor zeta
      have been localized in both the basal and suprabasal cells of the epithelium.
      This study examined the hypothesis that OGF is an autocrine growth factor. Using
      probe for preproenkephalin (PPE) mRNA that encodes OGF, and in situ hybridization
      techniques, silver grains related to PPE mRNA were detected in both basal and
      suprabasal cells of the central and peripheral cornea, limbus, and conjunctiva.
      No distinct regional differences in the presence or location of message, as
      reflected by the density and distribution of PPE mRNA signal, were noted. These
      results demonstrate that a growth factor known to serve as a tonic, inhibitory,
      and receptor-mediated influence on the epithelium of the ocular surface is
      derived in an autocrine manner, thereby permitting local control of homeostatic
      cellular replication.

PMID- 9593830
TI  - Enzymatic and chemical modifications of lipoprotein(a) selectively alter its
      lysine-binding functions.
AB  - The pathogenicity of lipoprotein(a) [Lp(a)] as a risk factor for cardiovascular
      disease may depend upon its lysine binding sites (LBS) which impart unique
      functions to Lp(a) not shared with low density lipoprotein. Biologically relevant
      modifications of Lp(a) were tested for alterations of LBS activity using two
      previously described functional assays, a LBS-Lp(a) immunoassay and a lysine
      Sepharose bead assay. In the LBS-Lp(a) immunoassay, minimal changes in the LBS
      activity of Lp(a) were observed after modification with lipoprotein lipase,
      sphingomyelinase, or phospholipase C. In contrast, a significant (p<0.003)
      increase in the LBS activity of Lp(a) occurred after phospholipase A2 (PLA2)
      treatment, and this increase was confirmed using the lysine-Sepharose bead assay.
      The increase depended upon the release of fatty acids from Lp(a) by PLA2. A
      decrease in the LBS activity of Lp(a) occurred after oxidation of Lp(a) with 2,2'
      azobis(2-amidinopropane) dihydrochloride (AAPH) (44% decrease), but CuSO4
      oxidation increased LBS activity (210%). N-acetylcysteine (NAC) treatment of
      Lp(a) decreased (48%) LBS activity while homocysteine treatment had no (89%)
      effect. Thus, modification of phospholipids and protein moieties can alter the
      LBS-activity of Lp(a). Such enzymatic and chemical modifications may contribute
      to the variability in LBS function of Lp(a) seen within the population.

PMID- 9593831
TI  - Glutamate-like immunoreactivity in ascending spinofugal afferents to the rat
      periaqueductal grey.
AB  - The midbrain periaqueductal gray is a key structure for the mediation of an
      integrated defence behaviour. Although a prominent role for glutamate in PAG
      mechanisms is supported by both behavioural and morphological studies, whether
      PAG afferents conveying somatosensory information constitute a source of
      glutamatergic input to the PAG remains unknown. Here, we have compared the
      projection pattern of orthogradely-labelled spinoannular fibres with the
      distribution of glutamate-like immunoreactivity in the PAG at the light
      microscopic level. Transaxonal labelling was observed throughout the whole
      rostrocaudal axis of the PAG except for the dorsolateral regions. Cell-processes
      and terminal-reminiscent puncta were strongly immunoreactive in all PAG regions,
      including the dorsolateral areas. To ascertain whether glutamate-immunoreactive
      puncta observed at light microscopy indeed constituted axon terminals of the
      spinoannular system, glutamate-like immunoreactivity was assessed in orthogradely
      labelled synaptic terminals using a post-embedding immunogold procedure for
      electron microscopy. Quantitative analysis of gold particle densities revealed
      over twice as strong an immunoreactivity in anatomically-identified spinoannular
      axon terminals as in dendrites postsynaptic to them, perikarya and inhibitory
      Gray II synapses, as well as an over 5-fold heavier immunolabelling than in glial
      profiles. These findings reveal that glutamate is accumulated in synaptic
      terminals of the spinoannular system, supporting a neurotransmitter role for this
      acidic amino acid in spinofugal afferents to the PAG.

PMID- 9593832
TI  - Role of cerebral blood flow in seizures from hyperbaric oxygen exposure.
AB  - Hyperbaric O2 exposure causes seizures by an unknown mechanism. Cerebral blood
      flow (CBF) may affect seizure latency, although no studies have demonstrated a
      direct relationship. Awake rats (male, Sprague-Dawley, 350-450 g), instrumented
      for measuring electroencephalographic activity (EEG) and CBF (laser-Doppler
      flowmetry), were exposed to 100% O2 at 4 or 5 atm (gauge pressure) until EEG
      seizures. Compression with O2 caused vasoconstriction to about 70% of control
      flow that was maintained for various times. CBF then suddenly, but transiently,
      increased at a time that was reliably related to seizure latency (r=0.8, p<0.01).
      Additional animals were treated with agents that have diverse pharmacology and
      their effects on CBF and latency were measured. Glutamate receptor antagonists MK
      801 (1 or 4 mg/kg) and ketamine (20-100 mg/kg) significantly increased CBF by 60
      80% and decreased seizure latency from about 17+/-8 min (+/-S.D.) in controls to
      5+/-1 and 6+/-2 min, respectively. In opposite, a nitric oxide synthase (NOS)
      inhibitor, N-nitro-L-arginine (NNA)(25 mg/kg) decreased CBF by about 25% and
      increased time to seizure to 60+/-16 min. If these effects occur in humans, non
      invasive measurement of CBF could potentially improve the safety and reliability
      of hyperbaric O2 usage in clinical and diving applications. It also appears that
      the effect of drugs on seizure latency can be explained, at least in part, by
      their effect on CBF.

PMID- 9593833
TI  - Large frequency potentiation induced by 2 Hz stimulation in the hippocampus of
      epileptic El mice.
AB  - El mouse has been found to be characteristics with hippocampal disinhibition, and
      has been suggested decrease in GABAergic synaptic transmission [Ono et al., Brain
      Res. 745 (1997) 165-172; Fueta et al. , Brain Res. 779 (1998) 324-328]. The
      efficacy of GABAergic synapses can be modulated in response to trains of low
      frequency stimulation. The frequency potentiation of a population spike (PS) and
      the field excitatory postsynaptic potential (fEPSP) induced by a low frequency
      stimulation (2 Hz for 15 s) were recorded for the CA3 subfield, and PS alone for
      the CA1 subfield and dentate gyrus. PS frequency potentiation was greater in El
      mice than in non-epileptic control ddY mice. Especially the CA3 subfield
      exhibited a high PS frequency potentiation (300+/-73%) compared to age-matched
      ddY mice (64+/-24%). However, EPSP frequency potentiation was similar in El and
      ddY mice. The degree of PS frequency potentiation in CA3 was decreased by the
      reduction of extracellular Ca2+ from 2 to 1 mM in both strains, suggesting
      presynaptic involvement. The potentiation in El mice was suppressed by
      AMPA/kainate type receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX),
      but more than half of the control value remained at 5 microM, whereas the
      potentiation in ddY mice was abolished at this concentration. N-methyl-d
      aspartate (NMDA) type receptor antagonist 3-3 (2-carboxypiperazine-4-yl) propyl-1
      phosphonate (10 microM; CPP) did not affect the potentiation. Bicuculline (5
      microM), GABAA receptor antagonist, did not increase the amplitude of PS during
      stimulation but induced epileptic (multiple PSs) potentials. High PS frequency
      potentiation of El mice was mimicked to the degree of that in ddY mice by a low
      dose of GABAB receptor agonist baclofen (3 microM). The suppression by baclofen
      was partially reversed by the antagonist saclofen (500 microM). The large
      frequency potentiation in young El mice, which do not have seizure
      susceptibility, indicates an intrinsic property in El mice. It is suggested that
      the high synchronization of CA3 neurons in El mice is due to a little activation
      of GABAB receptor activation and also to enhancement of non-NMDA type synaptic
      transmission.

PMID- 9593834
TI  - NMDA receptor antagonists potently suppress the spontaneous withdrawal signs
      induced by discontinuation of long-term diazepam treatment in Fischer 344 rats.
AB  - The present study investigated the effects of the NMDA receptor antagonists
      dizocilpine (MK-801) and ifenprodil on the appearance of diazepam withdrawal
      signs caused by discontinuation of long-term diazepam treatment using a drug
      admixed food (DAF) method in Fischer 344 rats. The total withdrawal score was
      significantly decreased by after-withdrawal treatment with dizocilpine or
      ifenprodil. Dizocilpine, in particular, markedly suppressed the motor withdrawal
      signs and body weight loss, while ifenprodil suppressed the motor and emotional
      withdrawal signs. Furthermore, the decrease in the food intake during withdrawal
      (anorexia) was significantly reduced by dizocilpine, but not by ifenprodil. These
      behavioral results indicated that the activation of NMDA receptors during
      withdrawal may play an important role in the appearance of withdrawal signs (in
      particular motor withdrawal signs) caused by discontinuation of chronic diazepam
      treatment, and that inhibitory agents for NMDA receptors may be effective in
      alleviation of the appearance of benzodiazepine withdrawal signs.

PMID- 9593835
TI  - The role of mu and kappa opioid receptors within the periaqueductal gray in the
      expression of conditional hypoalgesia.
AB  - The periaqueductal gray (PAG) is a midbrain structure involved in the modulation
      of pain and expression of classically conditioned fear responses. Non-selective
      opioid antagonists applied to the PAG block the expression of hypoalgesia in rats
      exposed to a Pavlovian signal for shock. This study was conducted to determine
      the anatomical and pharmacological specificity of the PAG's role in conditional
      hypoalgesia. Rat subjects received injections of either the mu opioid antagonist
      CTAP (6.6 nMol), the kappa opioid antagonist Nor-binaltorphimine (Nor-BNI, 6.6
      nMol) or saline. Injections were made into either the dorsolateral (dlPAG) or
      ventrolateral (vlPAG) PAG prior to the presentation of an auditory stimulus that
      had previously been paired with foot shock while measuring nociception with the
      radiant heat tail flick (TF) test. Elevation in TF latency in response to the
      auditory stimulus was blocked only by administration of CTAP into the vlPAG.
      These results suggest that conditional hypoalgesia (CHA) is subserved by mu but
      not kappa opioid receptors located in the vlPAG but not the dlPAG.

PMID- 9593836
TI  - Characterization of fatty acid synthase in cell lines derived from experimental
      mammary tumors.
AB  - The lipogenic enzyme fatty acid synthase (FAS) is elevated in various human
      primary cancers and certain human cancer cell lines. FAS overexpression in human
      neoplasia has clinical relevance because of its association with tumor aggression
      and potential chemotherapeutic intervention. Here, we surveyed FAS in cell lines
      established from normal murine mammary epithelium (NMuMG) and from mammary tumors
      induced by either rodent polyoma (Py) virus or murine mammary tumor virus (MMTV).
      Western blotting revealed greater content of FAS in Py-transformed A1-1 and T1
      than NMuMG or MMTV-transformed Mm5MT, RIIIMT and MMT060562. These data suggest
      that signaling events mediated by Py transformation may increase cellular amounts
      of FAS. Although FAS content was elevated to similar levels in A1-1 and T1,
      specific activities were significantly different as enzyme activity in T1 was 3
      fold higher than A1-1. Likewise, FAS activity in NMuMG was about 0.5-fold higher
      than the MMTV-transformed lines, even though enzyme content was similar.
      Immunoprecipitation studies employing anti-phosphoamino acid antibodies followed
      by immunoblot analysis with anti-FAS antisera (and vice versa) were used to
      characterize the constitutive phosphorylation state of the enzyme. Phosphoserine
      and phosphothreonine residues were detected in the more active FAS from T1 and
      NMuMG, but not in the less active FAS from Mm5MT or A1-1. Discovery of
      phosphorylated FAS suggests that the enzyme may have more immediate control over
      lipogenesis than previously thought. High-dose (10-4 M) dexamethasone induced FAS
      content and activity in NMuMG and MMTV-transformed lines but not Py-transformed
      cells. Lower concentrations (10-8, 10-6 M) of dexamethasone also activated FAS
      but without concomitant elevation of its protein content, which was consistent
      with a phosphorylated form of FAS. Finally, cell lines were treated with the FAS
      inhibitor cerulenin: almost all breast cancer lines were growth inhibited at
      significantly lower amounts of drug than normal cell lineages, suggesting that
      FAS plays a greater role in viability of tumor cells than normal cells.
      Pretreatment with palmitate (a primary end-product of FAS) prior to cerulenin
      rescued A1-1 cells only slightly from growth inhibition, whereas pretreatment
      with oleate (a monounsaturated fatty acid synthesized from palmitate) synergized
      cerulenin's cytotoxic effects.

PMID- 9593837
TI  - Complex I from the fungus Neurospora crassa.
AB  - Respiratory chain complex I is a complicated enzyme of mitochondria, that couples
      electron transfer from NADH to ubiquinone to the proton translocation across the
      inner membrane of the organelle. The fungus Neurospora crassa has been used as
      one of the main model organisms to study this enzyme. Complex I is composed of
      multiple polypeptide subunits of dual genetic origin and contains several
      prosthetic groups involved in its activity. Most subunits have been cloned and
      those binding redox centres have been identified. Yet, the functional role of
      certain complex I proteins remains unknown. Insight into the possible origin and
      the mechanisms of complex I assembly has been gained. Several mutant strains of
      N. crassa, in which specific subunits of complex I were disrupted, have been
      isolated and characterised. This review concerns many aspects of the structure,
      function and biogenesis of complex I that are being elucidated.

PMID- 9593838
TI  - Regulation of expression of neuropeptide Y Y1 and Y2 receptors in the arcuate
      nucleus of fasted rats.
AB  - Neuropeptide Y is expressed in neurons of the hypothalamic arcuate nucleus and
      has been ascribed a role as a stimulant of food intake. Neuropeptide Y Y1 and Y2
      receptors are also localised in the arcuate nucleus, and it has been suggested
      that the Y1 receptor mediates part of the effect of neuropeptide Y on feeding
      behaviour. In the present study, immunohistochemistry and in situ hybridization
      were used to investigate the effect of food deprivation on the expression of Y1
      and Y2 receptors in the arcuate nucleus of the rat. Fasting for 48 h induced a
      decrease in the number and area of Y1 receptor immunoreactive neurons in the
      arcuate nucleus. Furthermore, arcuate Y1 receptor mRNA levels also decreased
      after food deprivation. The decrease in the number of the Y1 receptor
      immunoreactive neurons was partially attenuated by supplementing the drinking
      water with 10% glucose. In contrast, fasting did not significantly change Y2
      receptor mRNA levels in the arcuate nucleus. These results support the view that
      Y1 receptors in the arcuate nucleus play a role in the feeding pattern induced by
      neuropeptide Y.

PMID- 9593839
TI  - Spontaneous and artificial lesions of magnocellular reticular formation of
      brainstem deteriorate avoidance learning in senescence-accelerated mouse SAM.
AB  - The role of the magnocellular reticular formation (MGRF) of the brainstem on
      learning and memory was examined in memory-deficient mice with spontaneous spongy
      degeneration in the brainstem (senescence-accelerated mouse, SAMP8) and control
      mice (accelerated-senescence resistant mouse, SAMR 1). SAMP8 showed spontaneous
      age-related impairment of learning and memory, as determined by passive and
      active avoidance responses. The deficits of learning and memory function in
      passive avoidance performances began at two months of age and increased with
      ageing. In the brains of SAMP8 at one month of age and older, spongy degeneration
      was mainly observed in the brainstem, while no vacuoles were evident in SAMR1
      control (normal ageing mouse) brains in the age range tested (up to 12 months).
      The vacuolization in SAMP8 was marked in the MGRF, especially in the dorsomedial
      MGRF. Quantitative analysis of the vacuolization showed that the total area and
      number of vacuoles in the MGRF increased with age, and they were affected by the
      degree of deficits in learning and memory. The latency 24 h after footshock in
      passive avoidance tests decreased with the increase in total area and number of
      vacuoles in MGRF. The number of shocks in active avoidance tests increased with
      the increase in total number and area of vacuoles. Thus, learning and memory
      ability in passive and active avoidance responses deteriorated with enlargement
      in the vacuolated area in MGRF, and it was assumed that MGRF (especially, the
      dorsomedial part) possesses functions related to learning and memory. To confirm
      this notion, behavior and memory tests (passive avoidance and active avoidance
      tests, open field tests and shock sensitivity measurements) were carried out in
      SAMR1 mice, whose bilateral dorsomedial MGRF was destroyed electrolytically (MGRF
      lesioned mice). The MGRF-lesioned mice showed no difference from sham mice in
      sensory threshold or open field activity; however, there was severe deterioration
      in passive avoidance behavior and impairment in the active avoidance
      performances. From the results in SAMP8 and MGRF-lesioned mice, it was confirmed
      that MGRF (especially the dorsomedial part) has functions related to learning and
      memory, and is one part in the learning and memory system of the brain. Thus,
      SAMP8 can serve as a model of RF-lesioned mice with impaired learning and memory
      functions.

PMID- 9593840
TI  - Effects of oxyhemoglobin in vitro in cerebral arteries from normal animals and
      animals subject to subarachnoid hemorrhage or indomethacin treatment.
AB  - Experiments were performed to test the hypothesis that subarachnoid hemorrhage
      (SAH) causes functionally relevant perturbations of cyclooxygenase activity in
      cerebral arteries. Four groups of rabbits were formed: (I) controls; (II) sham
      injected animals (2 ml physiological solution in the cisterna magna); (III) SAH
      group (2 ml blood in cisterna magna); (IV) indomethacin group (4 mg/kg i.v. 30
      min before sacrifice). Animals of groups II and III were used 3 days after
      injection. The basilar arteries (BAs) were removed and perfused at a constant
      flow rate (after electrocoagulation of all branches) in vitro in a 2-ml bath at
      37 degrees C. After 45 min equilibration, the arteries were subjected to a fixed
      protocol: first, in Krebs solution, contraction to increasing extraluminal
      concentrations of histamine (HA), followed by a single maximal extraluminal
      concentration of acetylcholine (ACh); then, after 30 min rest, the same tests
      were repeated in oxyhemoglobin (oxyHb) solution (extraluminal, 10-4 M). Perfusion
      pressure changes reflected changes in artery resistance. Although oxyHb alone
      increased pressure, indicating contraction of the arteries, its most important
      effect was to increase contraction to HA (in groups II, III, and IV but not
      controls) and to strongly inhibit ACh-induced relaxation in the SAH (-66.3%) and
      indomethacin (-46.9%) groups (III and IV) but not the control (-27.6%) group. The
      latter result suggests that a relaxing factor released by ACh in oxyHb solution
      in the control group was not present in groups III and IV. In conjunction with
      the results on HA, which is known to normally release prostacyclin (PGI2) from
      the endothelium, it is concluded that PGI2 was not or little released from
      arteries of the SAH group when they bathed in oxyHb solution. Alternatively, in
      the SAH group constrictor prostaglandins were released in response to HA and ACh
      in place of PGI2.

PMID- 9593841
TI  - Embryonic entorhinal transplants partially ameliorate the deficits in spatial
      memory in adult rats with entorhinal cortex lesions.
AB  - Our previous studies have demonstrated that axons from grafts of embryonic
      entorhinal cortex (EC) can reinnervate the deafferented zones in the hippocampus
      and form synaptic connections with the host dentate gyrus in adult mice and rats
      deprived of their own entorhinal inputs. Here, we have examined the ability of
      the EC grafts to ameliorate deficits in spatial memory. Three months after
      transplantation, the grafted rats and control animals were subjected to Morris
      water maze testing followed by histological examination. According to the exact
      position of grafts in the host brain, the rats with lesion and EC transplants
      were divided into two groups, one with EC grafts contacting both the hippocampus
      and overlying neocortex (n=7, EC1) and another with EC grafts confined within the
      hippocampus (n=6, EC2). While EC2 rats were still as impaired as those with
      lesion and transplants of non-entorhinal cortex (n=10, NEC) or with lesions only
      (n=7, LES), the EC1 rats performed better than the LES group. In a spatial memory
      trial, the EC1 group made more crossings over platform site and showed more
      focused search behavior than EC2, LES, NEC groups. The data suggest that EC
      grafts could partially ameliorate the deficit in spatial learning behavior in the
      EC-lesioned adult rats. The requirement for the graft to contact both the
      neocortex and the hippocampus suggests that the functional effects may be exerted
      by the formation of new neocortical-EC graft-hippocampal circuits.

PMID- 9593842
TI  - Hippocampal NMDA receptor mRNA undergoes subunit specific changes during
      developmental lead exposure.
AB  - The N-methyl-D-aspartate (NMDA) receptor has shown to play an important role in
      the cognitive deficits associated with developmental lead (Pb) exposure. In this
      study, we examined the effects of low-level Pb exposure on NMDA receptor subunit
      gene expression in the developing rat brain. The pattern of NR1, NR2A, NR2B, and
      NR2C subunit mRNA in situ hybridization was consistent with previous studies.
      Brain levels of NR1 and NR2A mRNAs were lowest shortly after birth, increasing to
      reach peak levels by 14 or 21 days of age and subsequently decreasing at 28 days
      of age. NR2B mRNA levels were highest during early development and decreased as
      the animals aged. NR2C subunit mRNA was restricted to the cerebellum and a signal
      was not detectable until the second week of life. Lead exposure resulted in
      significant and opposite effects in NR1 and NR2A subunit mRNA expression with no
      changes in NR2B or NR2C subunit expression. The Pb-induced changes in NR1 and
      NR2A subunit mRNA were mainly present in the hippocampus. Hippocampal NR1 mRNA
      levels were significantly increased in the CA1 (15.3%) and CA4 (26.8%) pyramidal
      cells from 14-day-old Pb-exposed rats. At 21 days of age, only the NR1 mRNA at
      the CA4 subfield remained significantly elevated (10.3%). Lead exposure caused
      reductions of NR2A mRNA levels (11.9-19.3%) in the pyramidal and granule cell
      layers of the hippocampus at 14 and 21 days of age. NR1 mRNA levels were also
      significantly increased (14.0%) in the cerebellum of 28-day-old rats with no
      change in NR2A mRNA at any age. No significant changes in subunit mRNA levels
      were present in cortical or subcortical regions at any age. The Pb-induced
      changes in hippocampal NMDA receptor subunit mRNA expression measured in the
      present study may lead to modifications in receptor levels or subtypes and alter
      the development of defined neuronal connections which require NMDA receptor
      activation.

PMID- 9593843
TI  - Non-opioid dynorphin binding site on secretory vesicles of a pituitary-derived
      cell line.
AB  - Accumulating evidence indicates that the endogenous opioid peptides dynorphinA-(1
      17) and dynorphinA-(1-13) interact not only with opioid but also with yet poorly
      characterized non-opioid receptors. The latter have been implicated in a number
      of the effects of dynorphins including induction of ACTH release in sheep and in
      AtT 20 cells, a pituitary-derived mouse cell line. AtT 20 cells do not express
      opioid receptors and therefore are particularly suitable for search of non-opioid
      dynorphin receptors. We report here that 3H-dynorphinA-(1-13)-NH2 associates
      specifically with AtT 20 cells, apparently through an uptake process and a
      binding site. Within the cell, it binds preferentially to fractions containing
      secretory vesicles, with a Kd of about 100 nM. DynorphinA-(1-17), and several non
      opioid fragments of dynorphin, including A-(2-17), A-(2-16) and A-(2-13), compete
      with 3H-dynorphinA-(1-13)-NH2 for that site with IC50s ranging from 200 nM to 2
      microM. ACTH(1-39) also competes with 3H-dynorphinA-(1-13)-NH2 for the site with
      an IC50 of about 300 nM. DynorphinA-(2-17) at microM concentrations stimulates
      release of ACTH from the isolated vesicles. The results indicate the presence of
      a non-opioid dynorphin binding site on the secretory vesicle fractions of AtT20
      cells that might be involved in ACTH release. The ability of ACTH itself to
      compete for the binding sites associated with the vesicles suggest that those
      sites may be involved in an autocrine loop.

PMID- 9593844
TI  - The use of sodium dodecyl sulfate to model the apolipoprotein environment.
      Evidence for peptide-SDS complexes using pulsed-field-gradient NMR spectroscopy.
AB  - Pulsed-field-gradient NMR spectroscopy was used to measure translational
      diffusion coefficients (Ds) for a peptide corresponding to a proposed lipid
      binding domain of human apolipoprotein C-I, residues 7-24 (apoC-I(7-24)).
      Diffusion coefficients for apoC-I(7-24) were determined directly by following the
      decay of the resonance intensity of selected peptide protons at various
      concentrations of sodium dodecyl sulfate (SDS), a detergent increasingly being
      used to model the apolipoprotein environment. Previously, diffusion coefficients
      of peptides in the presence of SDS have been determined indirectly by monitoring
      the SDS diffusion coefficient. The direct measurement of the diffusion
      coefficient of the peptide enables one to distinguish whether SDS simply coats
      the peptide's surface to produce a uniformly charged 'rod' or if the peptide
      associates with a micelle. Using the direct method, at SDS concentrations above 5
      mM (which is below the SDS critical micelle concentration (8.1 mM)), apoC-I(7-24)
      exhibited diffusion coefficients consistent with the formation of a large
      molecular-weight complex. Based on the ratio of the diffusion coefficients for
      free- and SDS-associated peptide, the molecular weight of the peptide-SDS complex
      was much larger than a factor of 1. 4, the increase in molecular weight of the
      free peptide predicted if apoC-I(7-24) was uniformly surface coated with SDS.

PMID- 9593845
TI  - Physiological, biochemical and molecular aspects of mitochondrial complex I in
      plants 
AB  - Respiratory complex I of plant mitochondria has to date been investigated with
      respect to physiological function, biochemical properties and molecular
      structure. In the respiratory chain complex I is the major entry gate for low
      potential electrons from matrix NADH, reducing ubiquinone and utilizing the
      released energy to pump protons across the inner membrane. Plant complex I is
      active against a background of several other NAD(P)H dehydrogenases, which do not
      contribute in proton pumping, but permit and establish several different routes
      of shuttling electrons from NAD(P)H to ubiquinone. Identification of the
      corresponding molecular structures, that is the proteins and genes of the
      different NADH dehydrogenases, will allow more detailed studies of this
      interactive regulatory network in plant mitochondria. Present knowledge of the
      structure of complex I and the respective mitochondrial and nuclear genes
      encoding various subunits of this complex in plants is summarized here. Copyright
      1998 Elsevier Science B.V.

PMID- 9593846
TI  - Dose-dependent, protective effect of FK506 against white matter changes in the
      rat brain after chronic cerebral ischemia.
AB  - Neuroprotective effects of immunosuppressive agents have been shown in cerebral
      ischemia. To investigate the role of immunosuppressive agents in chronic cerebral
      ischemia and to design a drug protocol with safe therapeutic windows, we examined
      the effects of FK506, a potent immunosuppressive agent, on chronic cerebral
      ischemia. Both common carotid arteries were ligated in 73 male Wistar rats. Fifty
      eight of these rats received a chronic injection of FK506 (0.2, 0.5, 1.0 mg/kg)
      and the remaining 15 received a vehicle solution injection. Microglia/macrophage
      was investigated with immunohistochemistry for leukocyte common antigen and major
      histocompatibility complex, and astroglia was examined with glial fibrillary
      acidic protein as markers. White matter rarefaction and the number of
      immunopositive glial cells were assessed from 7 to 30 days after the ligation. In
      the vehicle-treated animals, there was persistent and extensive activation of the
      microglia/macrophages and astroglia in the white matter, including the optic
      nerve, optic tract, corpus callosum, internal capsule, anterior commissure and
      traversing fiber bundles of the caudoputamen. In the FK506-treated rats, the
      number of activated microglia/macrophages was significantly reduced in a dose
      dependent manner (p<0.01) as compared to the vehicle-treated rats. Rarefaction of
      the white matter was also inhibited by FK506 in a dose-dependent manner (p<0.
      01). Thus, a clinically-relevant dosage of FK506 attenuated both glial activation
      and white matter changes in chronic cerebral ischemia in the rat. These results
      indicate a potential use for FK506 in cerebrovascular diseases.

PMID- 9593847
TI  - Spontaneous epileptiform bursts and long-term potentiation in rat CA3 hippocampal
      slices induced by chaotic stimulation of mossy fibers.
AB  - The relation between long-term potentiation (LTP) and spontaneous rhythm in CA3
      was investigated using rat hippocampal slices. Field potential response of CA3 to
      mossy fiber stimulation consisted of a mono-synaptic positive potential and
      subsequent poly-synaptic negative potentials. LTP of both field potentials was
      induced by chaotic mossy fiber stimulation. Although CA3 did not show any
      spontaneous rhythm before LTP induction in a normal perfusing medium, CA3
      spontaneously caused epileptiform bursts after LTP induction by chaotic mossy
      fiber stimulation. The amplitude of those epileptiform bursts and the inter-burst
      interval were not uniform. After LTP induction, the cross-correlation function of
      spontaneous field potentials simultaneously recorded at two sites approximately
      300 micron apart in CA3 showed a large central peak. This indicates that neuronal
      activity at two sites is synchronized. These results suggest that epileptiform
      bursts in CA3 are caused by synchronization of spontaneous CA3 pyramidal cell
      activity due to LTP induced by chaotic burst stimulation.

PMID- 9593848
TI  - The effects of neurosteroids on acquisition and retention of a modified passive
      avoidance learning task in mice.
AB  - This study examined the effects of neurosteroids, pregnenolone sulfate (PS) and
      dehydroepiandrosterone sulfate (DHEAS), on learning and memory processes in a
      modified passive-avoidance task in mice. The two parameters measured are number
      of passive-avoidance step-down descents and the active escape latency to reach
      shock-free zone. Each neurosteroid was administered 60 min before or immediately
      after the training session, or 60 min before the retention test given 24 h after
      acquisition. Pretraining injection of PS (0.125-10 mg/kg, s.c.) and DHEAS (0.125
      10 mg/kg, s.c.) decreased the number of mistakes committed on training day but
      had no effect on the latency measure. Both PS (0.125-10 mg/kg, s.c.) and DHEAS
      (0.125-10 mg/kg, s.c.) decreased the number of mistakes and latency to reach
      shock-free zone, in a dose-dependent and bell-shaped manner, following
      pretraining and posttraining administration schedules. Neurosteroids failed to
      improve memory performance when administered 60 min before retention testing.
      Injection of PS (0.5 and 1 mg/kg) or DHEAS (1 and 5 mg/kg) before both the
      training and test sessions, however, also significantly facilitated memory
      retention. In addition, the memory-facilitating effects of PS (0.5 mg/kg, s.c.)
      or DHEAS (1 mg/kg) when administered posttraining are blocked by concurrent
      administration of haloperidol (0.25 mg/kg, i.p.), a prototype sigma receptor
      antagonist. These results confirm that both PS and DHEAS facilitate retention of
      a modified learning task when given either pretraining or posttraining, but not
      prior to retention test. The pretraining neurosteroid-induced memory modulation
      do not involve state-dependent effects. These results suggest a role for central
      sigma receptor in the memory-modulating effects of neurosteroids.

PMID- 9593850
TI  - Organization and evolution of structural elements within complex I.

PMID- 9593849
TI  - Phorbol ester stimulation of phosphatidylcholine synthesis requires expression of
      both protein kinase C-alpha and phospholipase D.
AB  - The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA)
      stimulates both the synthesis and phospholipase D (PLD)-mediated hydrolysis of
      phosphatidylcholine (PtdCho). Here, attached and suspended NIH 3T3 fibroblasts as
      well as variants of the MCF-7 human breast carcinoma cell line expressing PKC
      alpha and a PtdCho-specific PLD activity at widely different levels were used to
      determine the possible role of PKC-alpha, PtdCho hydrolysis, and choline uptake
      in the mediation of PMA effect on PtdCho synthesis. In wild-type MCF-7 cells,
      which express both PKC-alpha and PLD activities at very low levels, PMA had
      little effects on the uptake or incorporation [14C]choline into PtdCho. In
      multidrug resistant MCF-7/MDR1 cells, which highly express PKC-alpha but lack the
      PtdCho-specific PLD activity, 100-nM PMA had relatively small stimulatory effects
      on the uptake of [14C]choline (approximately 1.5-fold) and [14C]PtdCho synthesis
      (1.5- to 2-fold). In NIH 3T3 fibroblasts and MCF-7/PKC-alpha cells, both
      expressing PKC-alpha and PLD activities at high levels, 10-100-nM PMA enhanced
      [14C]choline uptake only slightly (1.7- to 2.2-fold), while it had much greater
      (approximately 4-9-fold) stimulatory effects on PtdCho synthesis. PMA
      significantly enhanced the formation of phosphatidic acid (PtdOH) in MCF-7/PKC
      alpha cells (2.8-fold increase), but not in MCF-7/MDR1 cells (1.4-fold increase),
      while in both cell lines it had only small (1.3-1.5-fold) stimulatory effects on
      1,2-diacylglycerol (1, 2-DAG) formation. In suspended NIH 3T3 cells, 200-300-mM
      ethanol blocked the stimulatory effect of PMA on PtdOH formation without
      affecting PtdCho synthesis indicating that neither PtdOH nor 1,2-DAG derived from
      it is a mediator of PMA effect on PtdCho synthesis. In attached NIH 3T3 cells,
      dimethylbenz[a]anthracene enhanced phosphocholine formation and, thus, choline
      uptake without increasing PtdCho synthesis or modifying the effect of PMA. While
      the results indicate that the stimulatory effect of PMA on PtdCho synthesis
      requires the expression of both PKC-alpha and a PtdCho-specific PLD, they do not
      support a role for 1,2-DAG, PtdOH or choline in the mediation of PMA effect.

PMID- 9593851
TI  - Modulation of junctional conductance between rat carotid body glomus cells by
      hypoxia, cAMP and acidity.
AB  - Short-term cultures of glomus cells (up to seven days), were employed to study
      intercellular electrical communications. Bidirectional electric coupling was
      established under current clamping after impaling two adjacent glomus cells with
      microelectrodes, and alternate stimulation and recording. Their resting potential
      (Vm) and input resistance (Ro) were thus measured. Both coupled cells were then
      voltage clamped at a level between their Vms. Current pulses applied to either
      cell elicited a transjunctional voltage (Vj) and current (Ij), used to calculate
      the junctional conductance (Gj). Gj was 1.52+/-0.29 nS (mean+/-S.E.; n=147). Vj
      linearly influenced Gj, suggesting ohmic junctions. Gj was not affected by Vm in
      50% of the cases. However, there was Vm-dependence in the others, but voltage
      changes had to be large (>+/-40 mV from the Vm). Therefore, physiologically or
      pharmacologically induced glomus cell depolarization or hyperpolarization may not
      significantly affect intercellular coupling unless there are large variations in
      Vm. Hypoxia (induced by Na2S2O4 1 mM or 100% N2) decreased Gj in 60-80% of the
      pairs while producing tighter coupling in the rest. Similar effects were obtained
      when the medium was acidified with lactic acid 1-10 mM. Cobalt chloride (3 mM)
      prevented, diminished or reversed the changes in Gj observed during low PO2,
      suggesting that [Ca2+]i changes are important in hypoxic uncoupling. However, non
      specific cationic effects of Co2+ have not been ruled out. Applications of the
      membrane-permeant dB-cAMP 1 mM tightened coupling in almost all cell pairs. This
      is important because endogenous cAMP increases during hypoxia. Our results
      suggest that multiple factors modulate junctional conductance between glomus
      cells. Changes in Gj by 'natural' stimuli and/or cAMP may play an important role
      in chemoreception, especially in titrating the release of transmitters toward the
      carotid nerve terminals.

PMID- 9593852
TI  - Kinetics and distribution of [59Fe-125I]transferrin injected into the ventricular
      system of the rat.
AB  - We examined the kinetics and distribution of [59Fe-125I] rat Tf and unlabelled
      human Tf injected into a lateral cerebral ventricle (i.c. v. injection) in the
      rat. [56Fe-131I]Tf injected intravenously served as a control of blood-brain
      barrier (BBB) integrity. In CSF of adult rats, 59Fe and [125I]Tf decreased to
      only 2.5% of the dose injected after 4 h. In brain parenchyma, [125I]Tf had
      disappeared after 24 h, whereas approximately 18% of i.c.v.-injected 59Fe was
      retained even after 72 h. The elimination pattern of [125I]Tf from the CSF
      corresponded to that of [131I]albumin injected i.c.v., suggesting a nonselective
      washout of CSF proteins. [131I]Tf was hardly detectable in the brain, reflecting
      an unimpaired BBB during the experiments. Morphologically, 59Fe and i.c.v.
      injected human Tf were confined to the ventricular surface and meningeal areas,
      whereas grey matter regions at distances more than 2-3 mm from the ventricles and
      the subarachnoid space were unlabelled. However, accumulation of 59Fe was
      observed in the anterior thalamic and the medial habenular nuclei, and in brain
      regions with synaptic communications to these areas. In the newborn rats aged 7
      days (P7) injected i.c.v. with [59Fe-125I]Tf and examined after 24 h, the amounts
      of [125I]Tf in CSF were approximately 3.5 times higher than in adult rats
      collected after the same time interval, whereas the amounts of 59Fe in CSF were
      at the same level in P7 and adult rats. In the brain tissue of the i.c.v.
      injected P7 rats, both [125I]Tf and 59Fe were retained to a significantly higher
      degree compared to that seen in adult brains. The rapid washout and lack of
      capability for i.c.v. injected [125I]Tf to penetrate deeply into the brain
      parenchyma of the adult brain question the importance of Tf of the CSF, and
      choroid plexus-derived Tf, for Fe neutralization and delivery of Fe-Tf to TfR
      containing neurons and other cells in the CNS. However, it may serve these
      functions in young animals due to a lower rate of turnover of CSF.

PMID- 9593853
TI  - Pattern of synaptophysin immunoreactivity within mesencephalic grafts following
      transplantation in a parkinsonian primate model.
AB  - The majority of investigations into the degree of restoration of neural circuitry
      following transplantation of the embryonic ventral mesencephalon to the striatum
      have focused upon the particular neurochemical subtypes of the fibers exchanged
      between graft and host. Visualization of neurites of specific neurotransmitter
      type while informative regarding the specificity of graft-host interactions,
      vastly underrepresents overall synaptogenesis as it may occur in the grafting
      situation. The present approach of using a molecular marker characteristic of all
      normal, functional synapses provides broader information about the synaptic
      remodeling that occurs after tissue grafting. Synaptophysin (SY), an integral
      membrane protein of the synaptic vesicle, is a reliable marker of nerve terminal
      differentiation. Immunohistochemical staining with antibodies directed against SY
      and the dopamine synthetic enzyme tyrosine hydroxylase (TH) was used to assess
      overall synaptic differentiation as well as the relationship between SY
      immunoreactivity and the distribution of grafted dopamine (DA) neurons and
      processes in mesencephalic grafts and mesencephalic-striatal co-grafts implanted
      in the striatum of MPTP-treated African green monkeys. Grafted embryonic
      cerebellar tissue was used as a comparison graft type that does not normally
      exchange prominent direct projections with striatum. Dense pericellular arrays of
      SY-positive terminals were associated with TH-positive neurons in mesencephalic
      grafts. In mixed mesencephalic-striatal co-grafts, TH-positive fiber patches
      within the striatal portion of the graft demonstrated a high degree of
      correspondence with SY immunoreactivity. In contrast, grafts of cerebellar tissue
      did not display the same pattern of prominent pericellular arrays of SY staining.
      These observations suggest that functional synapses are abundantly present within
      grafted mesencephalon, and that these contacts are enriched in areas of the graft
      occupied by DA neurons. Implantation of an inappropriate striatal target, the
      cerebellum, results in visibly diminished innervation. The pattern of SY labeling
      observed suggests that tissue grafts are extensively innervated, probably both
      from extrinsic and intrinsic sources, and that the pattern and density of this
      innervation corresponds to the appropriateness of the graft-host interaction.

PMID- 9593854
TI  - Molecular cloning, expression in Escherichia coli, and characterization of a
      novel L-3-hydroxyacyl coenzyme A dehydrogenase from pig liver.
AB  - A novel L-3-hydroxyacyl-CoA dehydrogenase from pig liver has been cloned,
      expressed, purified, and characterized. This enzyme is a homodimer with a
      molecular mass of 65.6 kDa, and is distinguished from the dehydrogenase of pig
      heart by its structural features and catalytic properties. Its subunit,
      consisting of 302 amino acid residues, has two additional residues in a key
      region of the active center while it lacks a sequence of seven residues in the
      NAD+-binding domain, when compared with the subunit of pig heart enzyme. In
      addition, there are substitutions of four single residues. The catalytic
      efficiency of pig liver dehydrogenase was significantly greater than that of the
      heart enzyme for short-chain substrate, but its catalytic rates declined with an
      increase in substrate chain-lengths. The distinction between pig liver and heart
      dehydrogenases cannot be attributed to a species difference, and thus it is
      concluded that there exist different isoforms of monofunctional L-3-hydroxyacyl
      CoA dehydrogenases in pig. High level expression of mitochondrial L-3-hydroxyacyl
      CoA dehydrogenase in Escherichia coli has provided a very convenient way to
      purify this important beta-oxidation enzyme. There is substantial homology
      between pig liver dehydrogenase and various multifunctional beta-oxidation
      enzymes in the active center of these enzymes; a consensus sequence, HX3PX1
      3MXLXE, is proposed as the signature sequence of l-3-hydroxyacyl-CoA
      dehydrogenases.

PMID- 9593855
TI  - Expression of Fos protein in the limbic regions of the rat following haloperidol
      decanoate.
AB  - To identify sites of antipsychotic drug action, the effects of acute and chronic
      haloperidol treatment on Fos protein expression in rat brain regions were
      examined by immunohistochemical methods. Male Wistar rats were injected with
      haloperidol decanoate (40 mg/kg, i.m. ) or vehicle. Fourteen days after
      injection, each rat was given an acute subcutaneous injection of haloperidol
      (0.25 mg/kg) or vehicle, and was transcardially perfused 2 h after the second
      injection. A single dose of haloperidol to chronic vehicle-treated rats produced
      significant increases in Fos-positive neurons in 18 of 21 brain regions examined
      including the several cortical areas, caudate-putamen, nucleus accumbens, lateral
      septum, thalamic nuclei, amygdala, hippocampus CA1, mesencephalic dopaminergic
      nuclei, and periaqueductal grey. The rats treated with acute vehicle after
      chronic haloperidol showed persistent Fos increases in confined brain regions
      comprising the lateral and central amygdala, lateral septum, and entorhinal
      cortex. Additional haloperidol injection to the chronic haloperidol-treated rats
      induced significant increases in Fos immunoreactivity in more widespread limbic
      thalamo-cortical areas, whereas no significant increase was seen in the
      dorsolateral caudate-putamen. The persisting effects of haloperidol in the limbic
      and related structures, especially the amygdala, lateral septum, and entorhinal
      area may be of significance to the efficacy of long-term haloperidol treatment.

PMID- 9593856
TI  - Procaryotic complex I (NDH-1), an overview.

PMID- 9593857
TI  - Differential effects of NMDA and non-NMDA antagonists on the activity of aromatic
      L-amino acid decarboxylase activity in the nigrostriatal dopamine pathway of the
      rat.
AB  - This study examined the acute effects of a variety of NMDA and non-NMDA
      antagonists on the activity of aromatic l-amino acid decarboxylase (AADC) in the
      corpus striatum (CS) and substantia nigra (SN) of the rat. Sixty min pretreatment
      with the high affinity NMDA receptor-channel blockers MK 801 (0.01, 0.1 and 1
      mg/kg) and phencyclidine (4 mg/kg) elevated AADC activity in both the CS and SN
      (2- to 3-fold). Even more striking increases in AADC were noted with 40 mg/kg
      amantadine (3.8-fold for CS, 9.0-fold for SN), 40 mg/kg memantine (3.4-fold for
      CS, 3.1-fold for SN; 20 mg/kg no effect) and 40 mg/kg dextromethorphan (3.4-fold
      for CS, 6.2-fold for SN, in 6/10 'responders'). Similarly pronounced increases in
      AADC activity in CS (1.9-fold) and SN (2.8-fold) were detected after
      administering clonidine (2 mg/kg). R-HA 966 (5 mg/kg, not 1 mg/kg) modestly
      raised AADC activity in CS (0.45-fold) and not SN. Other drugs had no effect on
      the activity of the decarboxylase enzyme, including CGP 40116 (1 and 5 mg/g),
      eliprodil (10 mg/kg), NBQX (10 mg/kg, 30 min pretreatment) and atropine (1
      mg/kg). These experiments indicate that blocking the NMDA receptor-channel (and
      to a lesser extent the glycine site) or stimulating alpha2-adrenoceptors,
      profoundly increases AADC activity, more especially in the SN than CS. By
      contrast, inhibiting the NMDA glutamate recognition or polyamine sites, AMPA or
      muscarinic receptors is without effect on AADC in either brain region. The
      ability of amantadine and memantine to potentiate the antiparkinsonian actions of
      l-DOPA in the clinic, may be due to facilitated decarboxylation of l-DOPA by the
      brain.

PMID- 9593858
TI  - Role of protein kinase C alpha in endothelin-1 stimulation of cytosolic
      phospholipase A2 and arachidonic acid release in cultured cat iris sphincter
      smooth muscle cells.
AB  - We have investigated the role and mechanism of protein kinase C (PKC) isoforms in
      endothelin-1 (ET-1)-induced arachidonic acid (AA) release in cat iris sphincter
      smooth muscle (CISM) cells. ET-1 increased AA release in a concentration (EC50=8
      nM) and time-dependent (t1/2=1.2 min) manner. Cytosolic phospholipase A2 (cPLA2),
      but not phospholipase C (PLC), is involved in the liberation of AA in the
      stimulated cells. This conclusion is supported by the findings that ET-1-induced
      AA release is inhibited by AACOCF3, quinacrine and manoalide, PLA2 inhibitors,
      but not by U-73122, a PLC inhibitor, or by RHC-80267, a diacylglycerol lipase
      inhibitor. A role for PKC in ET-1-induced AA release is supported by the findings
      that the phorbol ester, PDBu, increased AA release by 96%, that prolonged
      treatment of the cells with PDBu resulted in the selective down regulation of
      PKCalpha and the complete inhibition of ET-1-induced AA release, and that
      pretreatment of the cells with staurosporine or RO 31-8220, PKC inhibitors,
      blocked the ET-1-induced AA release. Go-6976, a compound that inhibits PKCalpha
      and beta specifically, blocked ET-1-induced AA release in a concentration
      dependent manner with an IC50 value of 8 nM. Thymeatoxin (0.1 microM), a specific
      activator of PKCalpha, beta, and gamma induced a 150% increase in AA release.
      Treatment of the cells with ET-1 caused significant translocation of PKCalpha,
      but not PKCbeta, from cytosol to the particulate fraction. These results suggest
      that PKCalpha plays a critical role in ET-1-induced AA release in these cells.
      Immunochemical analysis revealed the presence of cPLA2, p42mapk and p44mapk in
      the CISM cells. The data presented are consistent with a role for PKCalpha, but
      not for p42/p44 mitogen-activated protein kinase (MAPK), in cPLA2 activation and
      AA release in ET-1-stimulated CISM cells since: (i) the PKC inhibitor, RO 31
      8220, inhibited ET-1-induced AA release, cPLA2 phosphorylation and cPLA2
      activity, but had no inhibitory effect on p42/p44 MAPK activation, (ii)
      genistein, a tyrosine kinase inhibitor, inhibited ET-1-stimulated MAPK activity
      but had no inhibitory effect on AA release in the ET-1-stimulated cells. We
      conclude that in CISM cells, ET-1 activates PKCalpha, which activates cPLA2,
      which liberates AA for prostaglandin synthesis.

PMID- 9593859
TI  - Regional differences between the immunohistochemical distribution of
      Ca2+/calmodulin-dependent protein kinase II alpha and beta isoforms in the
      brainstem of the rat.
AB  - The distribution of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II)
      alpha and beta isoforms in the brainstem of adult rats was investigated using an
      immunohistochemical method with two monoclonal antibodies which specifically
      recognize the alpha and beta isoform, respectively. We found that these isoforms
      were differentially expressed by neurons in the substantia nigra, red nucleus,
      dorsal cochlear nucleus, pontine nuclei and inferior olivary nucleus. Neurons in
      the inferior olivary nucleus express the alpha isoform, but not the beta isoform.
      In contrast, neurons in the substantia nigra, red nucleus and pontine nuclei were
      immunostained with the beta antibody, but not with the alpha antibody. In the
      dorsal cochlear nucleus, neurons in layers I and II were alpha-immunopositive,
      whereas neurons in layers III and IV were beta-immunopositive. Therefore, the
      distribution of the CaM kinase II alpha-immunopositive neurons is completely
      different from that of CaM kinase II beta-immunopositive neurons. Next we
      examined the possible coexistence of CaM kinase II alpha isoform and glutamate or
      that of CaM kinase II beta isoform and glutamic acid decarboxylase (GAD) in the
      single neuron by double immunofluorescence labelling using a pair of anti-alpha
      and anti-glutamate antibodies, or a pair of anti-beta and anti-GAD antibodies.
      The results indicated that neurons expressing anti-alpha immunoreactivity were
      also immunopositive against anti-glutamate antibody, and neurons expressing beta
      isoform were also immunopositive against anti-GAD antibody, suggesting that alpha
      immunopositive neurons are classified as excitatory-type neurons, and on the
      contrary, beta-immunopositive neurons are classified as inhibitory-type neurons.
      In conclusion, the present study confirmed that alpha- and beta-isoforms of CaM
      kinase II are differentially expressed in the nuclei of the brainstem and have
      different roles.

PMID- 9593860
TI  - Herpes virus-mediated preproenkephalin gene transfer to the amygdala is
      antinociceptive.
AB  - To evaluate the role of the amygdala in pain modulation and opioid-mediated
      antinociception, a recombinant, replication-defective herpes virus carrying the
      human preproenkephalin cDNA was injected bilaterally into the rat amygdala. Four
      days after gene delivery nociceptive behavior was assessed by the formalin test.
      Rats infected with the virus expressing preproenkephalin showed a selective,
      naloxone-reversible abolition of phase 2 flinching behavior compared to rats
      infected with a control virus. The results implicate the amygdala in the control
      of pain and in opioid analgesia and demonstrate the use of recombinant herpes
      viruses as tools for studying gene function in specific neural pathways of the
      central nervous system.

PMID- 9593861
TI  - The NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli.

PMID- 9593862
TI  - Effect of peripheral 2-DG on opioid and neuropeptide Y gene expression.
AB  - It is well known that 2-Deoxy-d-glucose (2-DG) blocks intracellular utilization
      of glucose and increases food intake. The aim of the present study was to
      determine whether administration of 2-DG alters gene expression of the orexigenic
      peptides, neuropeptide Y (NPY) and endogenous opioids, in the arcuate nucleus of
      the hypothalamus (ARC). Male Sprague-Dawley rats were injected peripherally
      (i.p.) with 2-DG (200 or 400 mg/kg body weight) and were sacrificed at 2 or 6 h
      post injection. Half of the animals were given ad libitum access to food whereas
      the other half of the animals were food-deprived. 2-DG increased food intake
      fourfold compared to saline injected animals, but did not affect NPY mRNA levels
      after 2 h. Messenger RNA levels of ProDynorphin (proDYN), but not pro
      opiomelanocortin (POMC) nor proEnkephalin (proENK) were significantly decreased 2
      h after 2-DG injection. Administration of 400 mg/kg of 2-DG increased mRNA levels
      of NPY in the arcuate nucleus after six h, but only in those animals not
      receiving food.

PMID- 9593863
TI  - Partial purification of a pramipexole-induced trophic activity directed at
      dopamine neurons in ventral mesencephalic cultures.
AB  - We previously demonstrated that media conditioned by exposure to ventral
      mesencephalic (VM) cultures in the presence of pramipexole (PPX) and other drugs
      with dopamine (DA) D3 properties, increased the growth and survival of DA neurons
      in recipient VM cultures. This trophic activity was heat-labile and not present
      in parietal cortex cultures or cultures pretreated with the DA neuron toxin MPP+.
      In an effort to begin to identify the protein(s) responsible for this trophic
      effect, we compared the conditioned media from normal VM cultures, VM cultures
      incubated with PPX, and VM cultures pretreated with MPP+ and treated with PPX.
      Neutralization studies using anti-GDNF and anti-BDNF failed to reduce the
      conditioned media transfer effect, and Millipore Ultrafree centrifugation studies
      placed the mol.wt. of the activity around 30 kDa. SDS separation revealed three
      potential bands of interest. A 35-kDa band was present in normal cultures,
      increased in PPX-incubated cultures, and absent in MPP+-pretreated/PPX-incubated
      cultures. This conforms to the effect the protein concentrates used to produce
      these gels had on the growth of DA neurons in VM cultures. Since VM cultures
      grown in neural basal media, which inhibits the growth of glia, still responded
      to PPX in a dose-dependent fashion, the trophic activity may be a DA autotrophic
      factor. However, the gels also revealed two bands at approximately 31 and 55 kDa
      that were reduced by exposure to PPX and present in MPP+-pretreated cultures. The
      possibility that these are neuroinhibitory factors that are also regulated by PPX
      therefore cannot be ruled out.

PMID- 9593864
TI  - Modulation of baroreflex sensitivity by the state of protein tyrosine
      phosphorylation in the brainstem of the rat.
AB  - Evidence accumulated recently suggests that protein tyrosine phosphorylation may
      play an important role in regulating neuronal functions. In the present study, we
      investigated if the state of protein tyrosine phosphorylation in the brainstem
      regulates baroreflex sensitivity. Anti-phosphotyrosine immunoblots of brainstem
      tissue revealed that several phosphotyrosine-containing proteins were present in
      the brainstem and their level of tyrosine phosphorylation was decreased by
      treatment of the slices with the protein tyrosine kinase (PTK) inhibitor
      genistein, and increased by treatment with the protein tyrosine phosphatase (PTP)
      inhibitor pervanadate. In urethane-anaesthetized rats, we found that inhibiting
      PTK activity by topical application of genistein to the dorsal surface of the
      medulla reduced the phenylephrine-induced baroreflex bradycardiac response.
      Conversely, the baroreflex response was potentiated by activating endogenous PTK
      activity with insulin or by inhibiting PTP activity with pervanadate. Thus these
      results suggest that the state of cellular tyrosine phosphorylation within the
      dorsal medulla of the brainstem may regulate the baroreflex control of heart
      rate, thereby providing the first evidence for a role for protein tyrosine
      phosphorylation, a key process involved in diverse intracellular signalling
      pathways, in modulating baroreflex sensitivity.

PMID- 9593865
TI  - Peripheral axotomy influences the in vivo release of cholecystokinin in the
      spinal cord dorsal horn-possible involvement of cholecystokinin-B receptors.
AB  - An increased expression of cholecystokinin (CCK) messenger RNA (mRNA) as well as
      CCK-B receptor mRNA in dorsal root ganglion (DRG) cells following peripheral
      axotomy has previously been demonstrated. In the present in vivo microdialysis
      study, the effect of unilateral sciatic nerve section on basal and potassium
      induced release of CCK-like (CCK-LI) immunoreactivity in the rat dorsal horn was
      investigated. We also compared the effects of the CCK-B receptor antagonist CI988
      on basal and potassium-stimulated CCK-LI release in intact animals and in
      chronically axotomized rats. Perfusion of the microdialysis probe with KCl (100
      mM) induced a more than 6-fold increase of the extracellular level of CCK-LI in
      control animals. In contrast, following unilateral sciatic nerve section the same
      KCl stimulation failed to evoke a release of CCK-LI ipsilaterally. However, after
      systemic administration of CI988 (1 mg kg-1, i.v.), 100 mM KCl induced a
      significant increase of the extracellular CCK-LI level in axotomized rats,
      similar to that observed in control animals. In control animals no effect of
      CI988 on KCl-stimulated CCK-LI release could be detected. CI988 by itself had no
      influence on the extracellular CCK-LI level in either nerve injured or control
      animals. The present data suggest that axotomy reduces the release of CCK-like
      immunoreactivity in the spinal cord by a mechanism involving the CCK-B receptor
      binding site.

PMID- 9593866
TI  - The role of platelet activating factor and other lipid mediators in inflammatory
      angiogenesis.
AB  - Chronic inflammatory diseases are often accompanied by intense angiogenesis. A
      model of inflammatory angiogenesis is the murine air pouch granuloma which has a
      hyperangiogenic component. Proinflammatory lipid mediator generation is also a
      hallmark of chronic inflammation and the role of endogenous production of these
      mediators in angiogenesis is not known. The 14 kDa phospholipase A2 (PLA2)
      deacylates phospholipid, liberating arachidonic acid, which is used for
      leukotriene production, and lysophospholipid, which can drive the production of
      platelet-activating factor (PAF). Therefore, SB 203347, an inhibitor of the 14
      kDa PLA2, zileuton, an inhibitor of 5-lipoxygenase, and Ro 24-4736 a PAF receptor
      antagonist were evaluated for their effects in the murine air pouch granuloma. SB
      203347 reduced both LTB4 and PAF, but not PGD2 levels measured in the day 6
      granuloma. This correlated with a significant reduction in angiogenesis. Zileuton
      reduced LTB4 levels as expected, but did not significantly inhibit angiogenesis,
      whereas Ro 24-4736 potently reduced angiogenesis. These data support the
      hypothesis that PAF, and to a lesser extent leukotrienes contribute to the
      angiogenic phenotype in chronic inflammation.

PMID- 9593868
TI  - The complex I from Rhodobacter capsulatus.
AB  - The NADH-ubiquinone oxidoreductase (type I NDH) of Rhodobacter capsulatus is a
      multisubunit enzyme encoded by the 14 genes of the nuo operon. This bacterial
      enzyme constitutes a valuable model for the characterization of the mitochondrial
      Complex I structure and enzymatic mechanism for the following reasons. (i) The
      mitochondria-encoded ND subunits are not readily accessible to genetic
      manipulation. In contrast, the equivalents of the mitochondrial ND1, ND2, ND4,
      ND4L, ND5 and ND6 genes can be easily mutated in R. capsulatus by homologous
      recombination. (ii) As illustrated in the case of ND1 gene, point mutations
      associated with human cytopathies can be reproduced and studied in this model
      system. (iii) The R. capsulatus model also allows the recombinant manipulations
      of iron-sulfur (Fe-S) subunits and the assignment of Fe-S clusters as illustrated
      in the case of the NUOI subunit (the equivalent of the mitochondrial TYKY
      subunit). (iv) Finally, like mitochondrial Complex I, the NADH-ubiquinone
      oxidoreductase of R. capsulatus is highly sensitive to the inhibitor piericidin-A
      which is considered to bind to or close to the quinone binding site(s) of Complex
      I. Therefore, isolation of R. capsulatus mutants resistant to piericidin-A
      represents a straightforward way to map the inhibitor binding sites and to try
      and define the location of quinone binding site(s) in the enzyme. These
      illustrations that describe the interest in the R. capsulatus NADH-ubiquinone
      oxidoreductase model for the general study of Complex I will be critically
      developed in the present review.

PMID- 9593867
TI  - Effect of nitric oxide synthase inhibitor on a hyperglycemic rat model of
      reversible focal ischemia: detection of excitatory amino acids release and
      hydroxyl radical formation.
AB  - The purpose of this study was to investigate the mechanisms by which a nitric
      oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), is
      neuroprotective in the hyperglycemic rat model of 2 h of transient middle
      cerebral artery occlusion followed by 2 h of reperfusion (MCAO/R). The salicylate
      trapping method was used in conjunction with a microdialysis technique to
      continuously estimate hydroxyl radical (.OH) formation by measurement of the
      stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA). Extracellular
      excitatory amino acids (EAAs) were detected from the same microdialysis samples.
      Magnetic resonance imaging (MRI) techniques were used to measure neuronal and
      cerebrovascular injury. The magnitude of EAA release correlated with the levels
      of the .OH adducts. Treatment with L-NAME (3 mg/kg, i.p.) 1 min before MCAO, and
      again 1 min before reperfusion, reduced the levels of DHBA by 46. 4% and
      glutamate by 50.5% in the hyperglycemic rats compared to untreated hyperglycemic
      controls. MRI indicated that L-NAME reduced the no-reflow zone and the cytotoxic
      lesion volume to 22.5% and 21. 0%, respectively, that of hyperglycemic controls.
      Co-treatment with the nitric oxide (NO) donor L-arginine completely eliminated
      the protective effects of l-NAME with respect to .OH and EAA levels as well as
      MRI lesion volume. Our data suggest that hyperglycemic MCAO/R results in
      excessive glutamate excitotoxicity, leading to enhanced generation of .OH via a
      NO-mediated mechanism, in turn resulting in severe ischemia/reperfusion brain
      injury.

PMID- 9593869
TI  - Co-localization of mu-opioid receptor-like immunoreactivity with substance P-LI,
      calcitonin gene-related peptide-LI and nitric oxide synthase-LI in vagal and
      glossopharyngeal afferent neurons of the rat.
AB  - Co-localization of mu-opioid receptor (MOR)-like immunoreactivity (-LI) with
      substance P (SP)-LI, calcitonin gene-related peptide (CGRP)-LI and nitric oxide
      synthase (NOS)-LI in the nodose, petrosal and jugular ganglia was examined in the
      rat by a double immunofluorescence histochemical method. About 0.6%, 41% and 95%
      of neurons with MOR-LI, respectively, in the nodose, petrosal and jugular ganglia
      showed SP-LI; about 2%, 51% and 66% of MOR-like immunoreactive neurons displayed
      CGRP-LI in the nodose, petrosal and jugular ganglia, respectively. In addition,
      about 59% of MOR-like immunoreactive neurons in the nodose ganglia displayed NOS
      LI, whereas no NOS-LI was detected in the petrosal or jugular ganglion. These
      data provide evidence for co-localization of MOR-LI with SP-LI, CGRP-LI and NOS
      LI in the vagal and glossopharyngeal afferent neurons, and suggest that MOR may
      regulate the release of SP, CGRP and nitric oxide from the visceral primary
      afferent terminals in the nucleus of the solitary tract of the rat.

PMID- 9593870
TI  - Neurally mediated hyperactive voiding in spontaneously hypertensive rats.
AB  - The development of hypertension in spontaneously hypertensive rats (SHR) and
      hyperactive voiding in rats with urethral obstruction are characterized by
      abnormal smooth muscle growth, increased tissue levels of nerve growth factor
      (NGF) and altered patterns of innervation. The present study was undertaken to
      determine if bladder smooth muscle from SHRs contains and secretes elevated
      levels of NGF, and if so, whether the augmented NGF contributes to changes in
      bladder innervation and function without tissue hypertrophy. Voiding behavior was
      monitored using specially designed metabolic cages. NGF levels in tissue
      homogenates and conditioned cell culture media were measured by ELISA. NGF mRNA
      in cultured bladder smooth muscle cells (BSMCs) was quantified using reverse
      transcriptase PCR. Noradrenergic innervation was assessed by staining with
      glyoxylic acid and assaying norepinephrine (NE) content in bladders with high
      performance liquid chromatography. SHRs voided more frequently than WKY rats. NGF
      content was higher in bladders from adult SHRs when compared to Wistar-Kyoto
      normotensive rats (WKYs). No significant difference in NGF mRNA content was
      observed between SHR and WKY BSMCs. However, SHR BSMCs secreted NGF at a higher
      rate and amount per unit mRNA than did WKY BSMCs. SHR bladders contained more NE
      and were more densely stained for catecholaminergic fibers than bladders from WKY
      rats. The results support the hypothesis that elevated NGF secretion by bladder
      smooth muscle is associated with hyperinnervation of bladder and hyperactive
      voiding in SHRs. Thus, the SHR strain may represent a genetic model to study
      changes in bladder function resulting from altered patterns of innervation.

PMID- 9593871
TI  - MK801-a neuroprotectant in rat hypertensive eyes.
AB  - Excitatory synaptic transmission in the mammalian CNS and retina is mainly
      mediated through l-glutamate. The effect of MK-801, a non-competitive antagonist
      of the NMDA subtype of glutamate receptor was studied on rat retinal ganglion
      cells in hypertensive eyes. MK-801 was administered intraperitoneally to the
      first group, 1 day before the increase, and in the second group, 2 days after the
      intraocular pressure (IOP) elevation. Phosphate-buffered saline was administered
      to the control group. Animals were sacrificed 2 and 4 weeks post-IOP increase.
      The retinal ganglion cells were counted and compared between control (right) and
      experimental (left) eyes. The data presented here suggests that MK-801 has
      neuroprotective properties.

PMID- 9593872
TI  - Fos expression in the brain induced by peripheral injection of CCK or leptin plus
      CCK in fasted lean mice.
AB  - We previously reported a synergistic interaction between leptin and
      cholecystokinin (CCK) to reduce food intake through CCK-A receptors in lean mice
      fasted for 24 h. To identify the activated neuronal pathways, we investigated
      changes in Fos expression in brain nuclei 2 h after single or combined
      intraperitoneal (i.p.) injections of leptin (120 microg/kg) and sulfated CCK-8
      (3.5 microg/kg) in male lean mice (C57BL/6) fasted for 24 h using
      immunohistochemistry for Fos, the protein product of the early gene, c-fos.
      Leptin did not increase Fos expression in the brain compared with vehicle-treated
      mice. CCK increased the numbers of Fos-positive neurons in the nucleus of the
      solitary tract (NTS)/area postrema (AP), central nucleus of the amygdala (CeA)
      and, to a smaller extent, in the paraventricular nucleus of the hypothalamus
      (PVN) (5.2-, 2.3- and 0. 3-fold respectively). Injections of leptin-CCK further
      enhanced Fos expression by 40% in the PVN compared with that induced by CCK
      alone, but not in the other nuclei. Devazepide (a CCK-A receptor antagonist, 1
      mg/kg, i.p.) prevented the increase in Fos expression induced by leptin-CCK in
      the PVN and by CCK alone in the PVN, CeA and NTS/AP. These results indicate that
      in fasted mice, i.p. injection of CCK increases Fos expression in specific brain
      nuclei through CCK-A receptors while leptin alone had no effect. Leptin in
      conjunction with CCK selectively enhanced Fos expression in the PVN. The PVN may
      be an important site mediating the synergistic effect of leptin-CCK to regulate
      food intake.

PMID- 9593873
TI  - Posture-dependent modulation of reciprocal inhibition upon initiation of ankle
      dorsiflexion in man.
AB  - The present study tested whether soleus H-reflex depression recorded from normal
      subjects during isotonic ankle dorsiflexion is due to reciprocal inhibition and
      this might be modulated by varying postures. The soleus H-reflex amplitude of
      eight healthy adults was investigated at various times prior to and during
      tibialis anterior discharge while subjects were seated and when standing. Results
      showed that the amount of soleus H-reflex depression was significantly larger in
      the standing than that in the sitting posture in spite of the same dorsiflexion
      movement. Furthermore, the depression upon initiation of dorsiflexion movement
      appeared earlier in the standing than in the sitting. The results suggest that
      increasing amounts of reciprocal inhibition are correlated with and dependent
      upon the preceding postural conditions for voluntary movement, i.e., modulation
      of reciprocal inhibition seems to be dictated by the difference in functional
      demand between sitting and standing posture.

PMID- 9593874
TI  - Evidence for the interaction of glutamate and NK1 receptors in the periphery.
AB  - It is known that Substance P (SP) enhances glutamate- and N-methyl-D-aspartate
      (NMDA)-induced activity in spinal cord dorsal horn neurons and that this
      enhancement is important in the generation of wind-up and central sensitization.
      It is now known that SP and glutamate receptors are present on sensory axons in
      rat glabrous skin. This raises the issue as to whether SP and glutamate interact
      in the periphery. Using the tail skin in rats, the present study demonstrates 1)
      that unmyelinated axons at the dermal-epidermal junction immunostain for
      antibodies directed against NMDA, non-NMDA or SP (NK1) receptors; 2) that
      glutamate injected into the tail skin results in dose-dependent nociceptive
      behaviors interpreted as mechanical hyperalgesia, mechanical allodynia and
      thermal hyperalgesia, which are blocked following co-injection with glutamate
      antagonists; 3) that peripheral injection of SP potentiates glutamate-induced
      nociceptive behaviors in that the co-injection of SP+glutamate results in a
      significantly longer duration of behavioral responses compared to the responses
      seen following injection of either substance alone. These data provide support
      for the hypothesis that primary afferent neurons might well be subject to similar
      mechanisms that result in wind-up or central sensitization of spinal cord
      neurons.

PMID- 9593875
TI  - Spinal cord transection induced c-fos protein in the rat motor cortex.
AB  - Spinal cord transection at the middle thoracic level induced the expression of c
      Fos protein in the rat motor cortex detected with the immunohistochemical study.
      At 1 h after transection, maximal expression of c-Fos was seen in the frontal
      cortex and hindlimb area of the cortex. c-Fos-like immunoreactive neurons were
      recognized in the second to sixth layers of these cortices, although the
      axotomized neurons were located only in the fifth layer of these cortices. A
      significant difference of c-Fos-like protein expression was observed between the
      spinal transected group and the sham operated group 1 h after the operation.
      These results indicate that each layer of the motor cortical column is activated
      and that there is a correlation between alteration of the neuronal network and
      functional plasticity.

PMID- 9593876
TI  - Ago-antagonist muscle spindle inputs contribute together to joint movement coding
      in man.
AB  - The proprioceptive feedback associated with the performance of even quite simple
      movements is always generated by the whole set of muscles subjected to mechanical
      deformation (lengthening, shortening, contraction, etc.) during that particular
      movement. The question was addressed here as to how muscle spindle feedbacks
      arising from agonist and antagonist muscles may contribute to the coding of
      movement parameters such as the direction and velocity. For this purpose, the
      activity of single muscle spindle afferents located in the lateral peroneal nerve
      was analysed using the microneurographic technique, in human subjects performing
      repetitive voluntary movements, i.e., plantar/dorsal flexions of the ankle, at
      three different velocities (3, 4.5 and 6 degrees/s). The data obtained suggest
      that in humans, the direction of a slow movement may be specified on the basis of
      the spindle discharge rate, which is greater in the stretched than in the
      shortened muscle, and that the velocity of this movement might be correlated with
      the difference between the spindle activity occurring in the agonist and
      antagonist muscles. These neurophysiological data are in agreement with the
      results of previous psychophysical studies showing for example that a sensation
      of illusory movement can be elicited only when there exists an imbalance between
      the agonist versus antagonist vibration-induced Ia inputs. In addition, the
      greater the difference between the vibration frequencies applied to the two
      antagonist muscles, the higher the perceived movement velocity was found to be.
      All in all, joint movement perception seems to result from the co-processing by
      the central nervous system of the multiple spindle feedbacks originating from the
      whole set of muscles involved in the performance of a movement.

PMID- 9593877
TI  - The influence of temporal summation on a C-fibre reflex in the rat: effects of
      lesions in the rostral ventromedial medulla (RVM).
AB  - In intact rats, an inhibitory mechanism counteracts the increase in excitability
      of a flexor reflex seen in spinal animals following high-intensity, repetitive
      stimulation of C-fibres. We tested the hypothesis that the rostral ventromedial
      medulla (RVM) is involved in these processes. Electromyographic responses
      elicited by electrical stimulation of the sural nerve, were recorded from the
      ipsilateral biceps femoris in halothane-anaesthetised, sham-operated or RVM
      lesioned rats. There were no significant differences between the C-fibre reflexes
      in the two groups in terms of their thresholds, latencies, durations or mean
      recruitment curves. The excitability of the C-fibre reflex was tested following
      20 s of high-intensity homotopic electrical conditioning stimuli at 1 Hz. During
      the conditioning period, the EMG responses first increased in both groups (the
      wind-up phenomenon), but then decreased in the sham-operated rats and plateaued
      in the RVM-lesioned rats. These effects were followed by inhibitions that were
      very much smaller in the RVM-lesioned rats, both in terms of their magnitudes and
      their durations. It is concluded that the RVM is involved in inhibitory feedback
      mechanisms elicited by temporal summation of C-fibre afferents that both
      counteract the wind-up phenomenon and trigger long periods of inhibition.

PMID- 9593878
TI  - Synaptic reorganization following kainic acid-induced seizures during
      development.
AB  - Prolonged seizures in the adult brain causes neuronal loss in the hippocampus and
      aberrant growth (sprouting) of granule cell axons (mossy fibers) in the
      supragranular zone of the fascia dentata and stratum infrapyramidale of CA3.
      There is considerable evidence that these changes in neuronal growth following
      seizures are age related, with younger animals having fewer reactive changes
      following prolonged seizures than older animals. However, there is little
      information available regarding the age at which seizures in the developing brain
      result in alterations in axonal growth and synapse formation. In this study, we
      evaluated the effects of kainic acid (KA)-induced seizures during development on
      synaptic reorganization using the expression of growth-associated protein-43 (GAP
      43), a marker for synaptogenesis and Timm stain which detects the presence of
      zinc in granule cell axons. Age specific doses of KA were used to induce seizures
      of similar intensity at various ages (postnatal days (P) 12, 21, 25, 35, 45, 60)
      in Sprague-Dawley rats. Up to the age of P25, there were no differences in either
      Timm or GAP-43 staining between animals with KA seizures and controls. In P25 and
      older KA-treated rats, Timm staining was found in the supragranular layer of the
      dentate gyrus. This staining increased with age at the time of KA injection.
      Seizures in adult (P60), but not younger rats also resulted in increased staining
      in the suprapyramidal layer of the CA3 subfields. Changes in GAP-43 were delayed
      compared to the Timm staining with no differences between KA-treated animals and
      controls until P35 when a band of GAP-43 immunostaining appeared in the
      supragranular inner molecular layer, progressively increasing in intensity and
      thickness with time. This study demonstrates that seizure-induced reactive
      synaptogenesis is age-related. Since both Timm and GAP-43 reflect different
      aspects of reactive synaptogenesis, used in combination these methods provide
      useful information about the structural changes following seizures during
      development.

PMID- 9593879
TI  - Catalytic properties of the mitochondrial NADH-ubiquinone oxidoreductase (complex
      I) and the pseudo-reversible active/inactive enzyme transition.

PMID- 9593881
TI  - Interocular effect of actin depolymerization on spinule formation in teleost
      retina.
AB  - Teleost retinas adapted to light show numerous spinules invaginated in the cone
      pedicles whereas darkness induces a reduction in the number of spinules.
      Horizontal cells show nematosomes whose size decreases as the number of spinules
      increases. We have investigated the involvement of actin filaments in spinule
      formation, by using cytochalasin D through intraocular injection into an eye. The
      ultrastructural analysis reveals that cytochalasin D impairs spinule formation
      and nematosome-size reduction in both treated and contralateral untreated
      retinas.

PMID- 9593880
TI  - Presynaptic inhibition by noradrenaline of the EPSC evoked in neonatal rat
      sympathetic preganglionic neurons.
AB  - Visually identified and electrophysiologically characterized sympathetic
      preganglionic neurons (SPNs) were recorded using the whole-cell voltage clamp
      technique in slices of neonatal rat spinal cord. Monosynaptic excitatory
      postsynaptic currents (EPSCs) were evoked by electrical stimulation of the
      nucleus intercalatus in the presence of strychnine (5 microM) and bicuculline (10
      microM). These EPSCs were abolished by the antagonist of AMPA-type glutamate
      receptors, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 10 microM). Bath applied
      noradrenaline (NA; 0.5-50 microM) dose-dependently and reversibly decreased by up
      to around 60% the amplitude of the EPSC, without affecting the holding current.
      The EPSC depression by NA was not accompanied by a change in EPSC reversal
      potential (around +5 mV), nor were inward currents generated by pressure
      application of glutamate affected by NA application. A comparable degree of EPSC
      depression was also seen with the alpha2-adrenoceptor agonist clonidine (5
      microM), and the alpha2A-agonist oxymetazoline (5 microM), while the alpha1
      agonist phenylephrine (100 microM) caused only a 22% depression. The EPSC
      depression caused by NA (10 microM) was completely antagonized by either the
      alpha-antagonist phentolamine (10 microM) or the alpha2-antagonist idazoxan (2
      microM). Conversely, the beta-adrenoceptor antagonist popranolol (5 microM), and
      the alpha1-, alpha2B- and alpha2C-antagonist prazosin (2 microM) were without
      effect. These results indicate that activation of presynaptic alpha2A
      adrenoceptors on inputs to SPNs decreases glutamate release.

PMID- 9593882
TI  - Age-dependent changes in adenosine receptors are not modified by life-long
      intermittent alcohol administration.
AB  - Autoradiography and in situ hybridisation were used to examine age-dependent
      changes in adenosine receptors in male rats and to determine if life-long (94
      weeks) intermittent ethanol consumption had any additional effect. Adenosine A2A
      receptors in striatum, as assessed by [3H]CGS 21680 binding, decreased by
      approximately 20% between the ages 6 and 99 weeks. Since dopamine D2 receptors
      and the mRNA for preproenkephalin also decreased there appears to be a loss of
      A2A-D2 receptor-bearing striatopallidal cells. Life-long ethanol consumption had
      no additional effect. Adenosine A1 receptors, as determined by [3H]DPCPX binding,
      did not decrease with age in any region of the brain, but increased slightly in
      the cerebellum. In substantia nigra, the increase in [3H]DPCPX binding upon
      addition of GTP was eliminated. Surprisingly, the amount of A1 receptor mRNA
      decreased significantly with age in most of the examined regions, including the
      cerebellum. There was no additional effect of ethanol treatment. It is suggested
      that age alters the number of cells that express A2A receptors, the turnover of
      A1 receptors, and in some regions their coupling to G proteins, but that life
      long intermittent ethanol exposure has little additional effect.

PMID- 9593883
TI  - Regulation of contextual conditioning by the median raphe nucleus.
AB  - The median raphe nucleus (MRN) has been suggested as the origin of a behavioral
      inhibition system that projects to the septum and hippocampus. Electrical
      stimulation of this mesencephalic area causes behavioral and autonomic
      manifestations characteristic of fear such as, freezing, defecation and
      micturition. In this study we extend these observations by analyzing the
      behavioral and autonomic responses of rats with lesions in the MRN submitted to a
      contextual conditioning paradigm. The animals underwent electrolytic or sham
      lesions of the median raphe nucleus. One day (acute) or 7 days (chronic) later
      they were tested in an experimental chamber where they received 10 foot-shocks
      (0.7 mA, 1 s with 20-s interval). The next day, sham and MRN-lesioned animals
      were tested again either in the same or in a different experimental chamber.
      During this, the duration of freezing, rearings, bouts of micturition and number
      of fecal boli were recorded. Sham-operated rats placed in the same chamber showed
      more freezing than rats exposed to a different context. This freezing behavior
      was clearly suppressed in rats with acute or chronic lesions in the MRN. MRN
      lesions also reduced the bouts of micturition and number of fecal boli. These
      rats showed a reduced number of rearings than sham-lesioned rats. This effect is
      probably the result of the displacement effect provoked by freezing since no
      significant differences in the number of rearings could be observed between these
      animals and the NMR-lesioned rats tested in an open field. This lesion produced
      higher horizontal locomotor activity in this test than the controls (sham
      lesioned rats). These results point to the importance of the median raphe nucleus
      in the processing of fear conditioning with freezing being the most salient
      feature of it. Behavioral inhibition is also under control of MRN but its neural
      substrate seems to be dissociated from that of contextual fear.

PMID- 9593884
TI  - Periaqueductal gray matter input to cardiac-related sympathetic premotor neurons.
AB  - The periaqueductal gray matter (PAG) serves as the midbrain link between
      forebrain emotional processing systems and motor pathways used in the defense
      reaction. Part of this response depends upon PAG efferent pathways that modulate
      cardiovascular-related sympathetic outflow systems, including those that regulate
      the heart. While it is known that the PAG projects to vagal preganglionic
      neurons, including possibly cardiovagal motoneurons, no information exists on the
      PAG circuits that may affect sympathetically mediated cardiac functions and,
      thus, the purpose of this study was to use neuroanatomical methods to identify
      these pathways. First, viral transneuronal retrograde tracing experiments were
      performed in which pseudorabies virus (PRV) was injected into the stellate
      ganglion of rats. After 4 days survival, five PAG regions contained
      transynaptically infected neurons; these included the dorsomedial, lateral and
      ventrolateral PAG columns as well as the Edinger-Westphal and precommissural
      nuclei. Second, the descending efferent PAG projections were studied with the
      anterograde axonal marker Phaseolus vulgaris leuco-agglutinin (PHA-L) with a
      particular focus on determining whether the PAG projects to the intermediolateral
      cell column (IML). Almost no axonal labeling was found throughout the thoracic
      IML suggesting that the PAG modulates sympathetic functions by indirect pathways
      involving synaptic relays through sympathetic premotor cell groups, especially
      those found in the medulla oblongata. This possibility was examined by a double
      tracing study. PHA-L was first injected into either the lateral or ventrolateral
      PAG and after 6 days, PRV was injected into the ipsilateral stellate ganglion.
      After an additional 4 days survival, a double immunohistochemical procedure for
      co-visualization of PRV and PHA-L was used to identify the sympathetic premotor
      regions that receive an input from the PAG. The PAG innervated specific groups of
      sympathetic premotor neurons in the hypothalamus, pons, and medulla as well as
      providing reciprocal intercolumnar connections within the PAG itself (Jansen et
      al., Brain Res. 784 (1998) 329-336). The major route terminates in the ventral
      medulla, especially within the medial region which contains sympathetic premotor
      neurons lying within the raphe magnus and gigantocellular reticular nucleus, pars
      alpha. Both serotonergic and non-serotonergic sympathetic premotor neurons in
      these two regions receive inputs from the PAG. Weak PAG projections to
      sympathetic premotor neurons were found in the rostral ventrolateral medulla
      (including to C1 adrenergic neurons), locus coeruleus, A5 cell group,
      paraventricular and lateral hypothalamic nuclei. In summary, both the lateral and
      ventrolateral PAG columns appear to be capable of modulating cardiac sympathetic
      functions via a series of indirect pathways involving sympathetic premotor
      neurons found in selected sites in the hypothalamus, midbrain, pons, and medulla
      oblongata, with the major outflow terminating in bulbospinal regions of the
      rostral ventromedial medulla.

PMID- 9593885
TI  - Developmental distribution of astrocytic proteins in the rat cochlear nucleus.
AB  - To investigate the developmental distribution of cochlear nucleus (CN)
      astrocytes, we used immunocytochemical localization of glial fibrillary acidic
      protein (GFAP) and S100beta in rats at 0, 5, 10, 15, 21, 30 postnatal days plus
      the adult. Differential developmental trends were observed for both proteins. The
      spatial distribution showed a progressive increase of the number of GFAP
      immunoreactive (GFAP-IR) astrocytes during development. GFAP positive cells
      occurred first in the granule cell domain of the ventral CN and in the molecular
      cell layer of the dorsal CN, then followed an outside to inside pattern of
      progression. The GFAP-IR reached an adult distribution 1 month after birth. By
      contrast with GFAP, the apparition of S100beta-immunoreactivity (S100beta-IR) was
      abrupt (between 0 and 5 days) followed by a rapid stabilization of density and
      distribution of IR cells (between 15 and 21 days). The developmental distribution
      of S100beta-IR cells occurred from the posterodorsal region and progressed toward
      a rostroventral direction. With contrast to GFAP-IR astrocytes, S100beta-positive
      cells were mainly restricted to the central part of the CN, while only few IR
      astrocytes were observed in the granule cell domain of the ventral CN or in the
      molecular cell layer of the dorsal CN. This differential distribution suggests
      that both antigens were expressed by two different cell populations at least, it
      is obvious during the first postnatal week. The gradual expression of GFAP and
      S100beta is interpreted as reflecting the time course of astrocytic maturation.
      These data suggest that the maturation of CN astrocytes may be linked to the
      final maturation of CN neurons.

PMID- 9593886
TI  - Intraaccumbens injections of substance P, morphine and amphetamine: effects on
      conditioned place preference and behavioral activity.
AB  - The nucleus accumbens of the rat plays a critical role in behavioral activation
      and appetitive motivation. Within the nucleus accumbens, the shell subarea may be
      especially relevant, since this site is anatomically related to other brain areas
      that are considered to play a critical role in the processing of motivation. We
      investigated the behavioral effects of local drug treatments aimed at the shell
      of the nucleus accumbens and tested the indirect dopamine agonist d-amphetamine,
      the opiate agonist morphine, and the neurokinin substance P. These substances are
      known to exert positive reinforcing effects, and can affect behavioral activity;
      effects that are physiologically closely related to the nucleus accumbens and its
      inputs and outputs. Our results show that unilateral microinjections of
      amphetamine (1.0 microg, 10.0 microg) into the shell of the nucleus accumbens
      dose-dependently stimulated behavioral activity (locomotion, rears, sniffing),
      and led to conditioned place preference. Furthermore, the effect of amphetamine
      on place preference was negatively related to the psychomotor stimulant action on
      rears. Morphine injections (5.0 microg) also stimulated behavioral activity and
      elicited contraversive turning, but were ineffective with respect to place
      preference. Finally, the neuropeptide substance P, injected in a dose range of
      0.1-10.0 ng, had no significant behavioral effects. These findings are discussed
      with respect to the role of dopaminergic, peptidergic and cholinergic mechanisms
      in the nucleus accumbens. It is suggested that dopamine, opiates, and neurokinins
      in the shell of the nucleus accumbens are differentially involved in mediating
      behavioral activity and appetitive motivation.

PMID- 9593887
TI  - Iron-sulfur clusters/semiquinones in complex I.
AB  - NADH-quinone 1 oxidoreductase (Complex I) isolated from bovine heart mitochondria
      was, until recently, the major source for the study of this most complicated
      energy transducing device in the mitochondrial respiratory chain. Complex I has
      been shown to contain 43 subunits and possesses a molecular mass of about 1
      million. Recently, Complex I genes have been cloned and sequenced from several
      bacterial sources including Escherichia coli, Paracoccus denitrificans,
      Rhodobacter capsulatus and Thermus thermophilus HB-8. These enzymes are less
      complicated than the bovine enzyme, containing a core of 13 or 14 subunits
      homologous to the bovine heart Complex I. From this data, important clues
      concerning the subunit location of both the substrate binding site and intrinsic
      redox centers have been gleaned. Powerful molecular genetic approaches used in
      these bacterial systems can identify structure/function relationships concerning
      the redox components of Complex I. Site-directed mutants at the level of
      bacterial chromosomes and over-expression and purification of single subunits
      have allowed detailed analysis of the amino acid residues involved in ligand
      binding to several iron-sulfur clusters. Therefore, it has become possible to
      examine which subunits contain individual iron-sulfur clusters, their location
      within the enzyme and what their ligand residues are. The discovery of g=2.00 EPR
      signals arising from two distinct species of semiquinone (SQ) in the activated
      bovine heart submitochondrial particles (SMP) is another line of recent progress.
      The intensity of semiquinone signals is sensitive to DeltamicroH+ and is
      diminished by specific inhibitors of Complex I. To date, semiquinones similar to
      those reported for the bovine heart mitochondrial Complex I have not yet been
      discovered in the bacterial systems. This mini-review describes three aspects of
      the recent progress in the study of the redox components of Complex I: (A) the
      location of the substrate (NADH) binding site, flavin, and most of the iron
      sulfur clusters, which have been identified in the hydrophilic electron entry
      domain of Complex I; (B) experimental evidence indicating that the cluster N2 is
      located in the amphipathic domain of Complex I, connecting the promontory and
      membrane parts. Very recent data is also presented suggesting that the cluster N2
      may have a unique ligand structure with an atypical cluster-ligation sequence
      motif located in the NuoB (NQO6/PSST) subunit rather than in the long advocated
      NuoI (NQO9/TYKY) subunit. The latter subunit contains the most primordial
      sequence motif for two tetranuclear clusters; (C) the discovery of spin-spin
      interactions between cluster N2 and two distinct Complex I-associated species of
      semiquinone. Based on the splitting of the g1 signal of the cluster N2 and
      concomitant strong enhancement of the semiquinone spin relaxation, one
      semiquinone species was localized 8-11 A from the cluster N2 within the inner
      membrane on the matrix side (N-side). Spin relaxation of the other semiquinone
      species is much less enhanced, and thus it was proposed to have a longer distance
      from the cluster N2, perhaps located closer to the other side (P-side) surface of
      the membrane. A brief introduction of EPR technique was also described in
      Appendix A of this mini-review.

PMID- 9593888
TI  - Alterations with aging and ischemia in nicotinic acetylcholine receptor subunits
      alpha4 and beta2 messenger RNA expression in postmortem human putamen.
      Implications for susceptibility to parkinsonism.
AB  - Nicotine activates the dopaminergic system and acts to alleviate hypokinetic
      disorders (parkinsonism). The frequency of parkinsonism increases with age and is
      sometimes associated with multiple small infarcts (status lacunaris) in the
      putamen. To investigate changes with aging in control cases free from
      neurological disease and changes in cases with multiple small infarcts (status
      lacunaris) in the putamen, the present study determined nicotinic acetylcholine
      receptor (nAChR) subunit alpha4 and beta2 messenger RNA (mRNA) expression in the
      postmortem human putamen using the reverse transcription-polymerase chain
      reaction (RT-PCR). In controls, alpha4 subunit mRNA expression was unaltered, but
      beta2 subunit mRNA expression decreased significantly with age. In cases with
      status lacunaris, both beta2 and alpha4 subunit mRNA expressions were
      significantly lower than in the control cases. The reduction in beta2 mRNA
      expression alone, or in both alpha4 and beta2 mRNA expressions, suggests a
      reduction in functional nAChRs in the putamen, which may in part explain the
      susceptibility to hypokinetic disorders of the elderly and subjects with ischemic
      damage in the striatum.

PMID- 9593889
TI  - Expression of NOS, PSA-N-CAM and S100 protein in the granule cell migration
      pathway of the adult guinea pig forebrain.
AB  - To investigate the possible role of nitric oxide (NO) in adult neurogenesis and
      neuron-glial migration in the rostral migratory stream (RMS), we used a double
      labeled immunofluorescence technique together with confocal laser scanning
      microscopy, and examined the localization of nitric oxide synthase (NOS), the
      highly polysialylated isoform of neural cell adhesion molecule (PSA-N-CAM), and
      the astroglial marker in brain, S100 protein (S100), throughout the length of the
      subependymal layer (SEL) to olfactory bulb (OB) pathway of the adult guinea pig
      forebrain. Blast-like, beaded, clustered immature cellular elements stained for
      PSA-N-CAM and those having a typical astrocytic phenotypes positive for S100
      protein were densely interlaced throughout the entire length of the SEL. Some
      S100 positive ependymoglial cells (tanycytes) gave off their basal projections
      into the closely packed PSA-N-CAM immunopositive clusters in the rostral
      extension of the subependymal zone (SEZre). The SEL was devoid of NOS
      immunoreactivity. A dense network of punctate, fenestrated and radially oriented
      immature cellular elements positive both for NOS and PSA-N-CAM intermingled and
      overlapped in the inner part of the internal granular layer (IGr), whereas in the
      outer part, PSA-N-CAM expression gradually diminished and the cells shifted to
      mature bipolar, spherical or spindle-shaped granule cells with uniform cellular
      contours, which were exclusively immunopositive for NOS. Radially oriented
      astroglial phenotypes were intertwined with PSA-N-CAM neuronal clusters in the
      SEL, and were closely apposed to NOS neuronal elements in the IGr. In summary,
      these results showed a distinct separation of neurons and glia as revealed by PSA
      N-CAM and S100 protein immunostaining, and an inverse spatio-temporal correlation
      of expression between PSA-N-CAM (immature neuroblasts) and NOS (mature neurons)
      in the adult guinea pig RMS.

PMID- 9593890
TI  - Effect of metabotropic glutamate receptor activation on receptor-mediated cyclic
      AMP responses in primary cultures of rat striatal neurones.
AB  - Co-activation of group I metabotropic glutamate (mGlu) receptors and adenosine
      receptors resulted in an augmented cyclic AMP response in primary cultures of rat
      striatal neurones. L-glutamate and the selective group I agonist, (S)
      dihydroxyphenylglycine (S-DHPG) evoked concentration-dependent potentiations of
      cyclic AMP accumulation stimulated by the adenosine receptor agonist, 5'-N
      ethylcarboxamidoadenosine (NECA), with EC50 values of 3.41+/-0. 39 and 5.69+/
      1.64 microM, respectively, and maximal augmentations of approximately 350% at
      concentrations of 100 microM. The S-DHPG potentiation was inhibited by group I
      mGlu receptor antagonists and a protein kinase C inhibitor, Ro 31-8220,
      implicating products of PI hydrolysis in this effect. Furthermore, L-glutamate
      and S-DHPG stimulated PI hydrolysis in striatal neuronal cultures with similar
      EC50 values to those observed for the augmentation of NECA cyclic AMP responses
      (5.19+/-1.18 and 3.78+/-1.42 microM, respectively). In situ hybridization and
      immunofluorescence techniques indicate that group I mGlu receptor-evoked
      potentiations are likely to be mediated via mGlu5 receptors, which are expressed
      at high levels in these cultures. In contrast to cross-chopped slices of neonatal
      rat striatum, of equivalent age, the group II mGlu receptor agonist, (2S,
      2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) was without effect on
      NECA- or forskolin-stimulated cyclic AMP responses in primary striatal neuronal
      cultures. This lack of effect might be due to a low level of expression of group
      II mGlu receptors in cultured striatal neurones.

PMID- 9593892
TI  - Timing of motion representation in the human visual system.
AB  - Visual stimulus in apparent motion evokes a magnetic field from the extrastriate
      cortex in humans. To investigate what this magnetic field represents, we measured
      the latencies of the responses in three subjects to the stimuli in apparent
      motion at various spatial separations. These different latencies were inversely
      related to the spatial separations of the stimuli (range of 74 to 182 ms) and
      correlated with each subject's reaction time. The direction of motion affected
      neither the latency of the magnetic response nor the reaction times. Estimations
      of the origins of the evoked magnetic fields showed they were always in the same
      area. In two subjects, the sites were around the meeting point of the ascending
      limb of the inferior temporal sulcus and the lateral occipital sulcus. In the
      third subject, the site was in the vicinity of the angular gyrus. The difference
      between the magnetic response and reaction time was fairly constant (about 64 ms)
      among the subjects. We consider the magnetic response to be related to the
      generation of a motion image: First, the response clearly corresponded to human
      reaction times to the same stimuli: Second, the fact that the magnetic response
      was related to the spatial separations but independent of the direction of motion
      is not explained if the response is evoked simply by both the onset and offset of
      the object in the stimulus. Furthermore, individual reaction times were mainly
      delayed by the speed of the process that generated the motion image.

PMID- 9593891
TI  - Substance P attenuates and DAMGO potentiates amygdala glutamatergic
      neurotransmission within the ventral pallidum.
AB  - The amygdala (AMG), nucleus accumbens (NA) and ventral pallidum (VP) influence
      goal-oriented behaviors. However, the nature of the interactions among these
      regions has not been well characterized. Anatomical studies indicate that
      excitatory amino acids are contained in VP inputs from the AMG, and the NA is a
      primary source of VP substance P (SP) and opioids. The present study was designed
      to functionally characterize the NA and AMG projections to the VP, and to assess
      if opioids and SP can modulate AMG-mediated excitatory neurotransmission within
      the VP. To do so, extracellularly recorded electrophysiological responses of
      single VP neurons to electrical activation of VP afferents were monitored during
      microiontophoretic application of treatment ligands in chloral hydrate
      anesthetized rats. The anatomically described glutamatergic inputs from the AMG,
      and SP inputs from the NA, were pharmacologically verified. It also was
      determined that even though iontophoretically applied SP increased the
      spontaneous activity of VP neurons, at ejection current levels that were below
      those necessary to produce this effect (termed sub-threshold), the tachykinin
      attenuated AMG stimulation-evoked glutamatergic neurotransmission. SP failed to
      modulate the excitations induced by iontophoretically applied glutamate
      suggesting that SP modulation of AMG-evoked excitations were mediated via a
      decrease in the pre-synaptic release of glutamate. Like SP, the effects of sub
      threshold ejection currents of micro opioid agonist DAMGO on AMG-evoked responses
      were not predicted by the opioid's effects on spontaneous VP neuronal activity;
      DAMGO inhibited spontaneous firing but potentiated AMG-evoked glutamatergic
      neurotransmission. The opioid also potentiated effects of exogenous glutamate
      implying an interaction at a post-synaptic site. These results indicate that
      tachykinin and opioid neuropeptides contained in NA projection neurons can
      differentially modulate AMG glutamatergic inputs to the VP.

PMID- 9593893
TI  - Serial processing of the somesthetic information revealed by different effects of
      stimulus rate on the somatosensory-evoked potentials and magnetic fields.
AB  - In order to evaluate information processing in the somatosensory cortex, the
      effect of two different stimulus rates was investigated by simultaneously
      recording somatosensory-evoked potentials (SEPs) and magnetic fields (SEFs) in
      nine healthy adults. During electric stimulation of the median nerve at the
      wrist, SEFs were recorded with the helmet-shaped whole-head coverage magnetometer
      array with 122 first-order planar gradiometers while SEPs were simultaneously
      recorded from seven scalp positions. Interstimulus intervals (ISIs) of 0.9 s and
      4 s were compared. In all subjects, N20 as well as its magnetic counterpart,
      N20m, was clearly demonstrated over the contralateral somatosensory area.
      Subsequent deflections around 80-200 ms did not make any clear peak and were
      smaller than those at 20-60 ms (P30m, P40m, N50m and P60m). After 200 ms, SEFs
      were negligible, whereas SEPs had larger amplitude than those of shorter
      latencies, constituting a peak around 250 ms (P250). Both SEF and SEP deflections
      later than 40 ms were decreased in responses at the shorter ISI; this diminution
      was most prominent for P250. Therefore, it is concluded that the tangential
      currents in the somatosensory cortex (area 3b) mainly contribute to responses
      during the first 200 ms after the stimulus, whereas the radially oriented
      currents (most likely in the crown of the postcentral gyrus) take over for
      subsequent information processing.

PMID- 9593894
TI  - Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and
      inhibits lipid peroxidation in different regions of the rat brain.
AB  - The free radical hypothesis for the pathogenesis and/or progression of
      Parkinson's disease (PD) has gained wide acceptance in recent years. Although it
      is clear that dopamine (DA) agonists cannot completely replace levodopa therapy,
      they can be beneficial early in the course of PD by reducing the accumulation of
      DA which undergoes auto-oxidation and generates cytotoxic free radicals. In the
      present study we demonstrate that pergolide, a widely used DA agonist, has free
      radical scavenging and antioxidant activities. Using a direct detection system
      for nitric oxide radical (NO.) by electron spin resonance (ESR) spectrometry in
      an in vitro .NO-generating system, we examined the quenching effects of pergolide
      on the amount of NO. generated. Pergolide dose-dependently scavenged NO.. In the
      competition assay, the IC50 value for pergolide was estimated to be about 30
      microM. Pergolide also dose-dependently attenuated the hydroxyl radical (.OH)
      signal in an in vitro FeSO4-H2O2 ESR system with an approximate IC50 value of 300
      microM. Furthermore, this agent significantly inhibited phospholipid peroxidation
      of rat brain homogenates in in vitro experiments and after repeated
      administration (0.5 mg/kg/24 h, i.p. for 7 days). Our findings suggest a
      neuroprotective role for pergolide on dopaminergic neurons due to its free
      radical scavenging and antioxidant properties.

PMID- 9593895
TI  - Quinone specificity of complex I.
AB  - This review considers the interaction of Complex I with different redox
      acceptors, mainly homologs and analogs of the physiological acceptor, hydrophobic
      Coenzyme Q. After examining the physical properties of the different quinones and
      their efficacy in restoring mitochondrial respiration, a survey ensues of the
      advantages and drawbacks of the quinones commonly used in Complex I activity
      determination and of their kinetic properties. The available evidence is then
      displayed on structure-activity relationships of various quinone compounds in
      terms of electron transfer activity and proton translocation, and the present
      knowledge is discussed in terms of the nature of multiple quinone-binding sites
      in the Complex.

PMID- 9593896
TI  - A comparison of the density of NADPH-diaphorase-reactive neurons in the fascia
      dentata and Ammon's horn between 6-month and 12-month old dark agouti rats.
AB  - The present study aimed to assess the developmental progress of the hippocampal
      nitric oxide (NO) system within adulthood by comparing the density of NO
      producing neurons in the fascia dentata and Ammon's horn in two groups of adult
      male rats using NADPH-diaphorase (NADPH-d) histochemistry. One group comprised 6
      month-old rats (early adulthood), and the other 12-month-old rats (middle
      adulthood). Areal density (number of neurons per unit area) of NADPH-d positive
      neurons along the three hippocampal axes (septo-temporal, transverse and radial
      axes) were subjected to quantitative analyses. There were significant variations
      in the density of NADPH-d-reactive neurons along the transverse and radial axes
      of the hippocampus, similar to what have been described previously. Comparison
      between 6-month and 12-month-old rats indicated a substantial reduction in the
      density of NADPH-d-reactive neurons in the fascia dentata (69%) and Ammon's horn
      (54%) of the latter group. This reduction was relatively uniform along the
      septotemporal and radial axes, but appeared to be more pronounced in the fascia
      dentata and in the proximal region of Ammon's horn. Our finding showed that the
      hippocampal NO system can undergo significant changes within adulthood. It
      further highlighted the possibility that an age-related reduction in the capacity
      to produce NO may not be directly responsible for the cognitive decline
      associated with senescence, but rather predisposes neuronal degeneration in later
      life.

PMID- 9593897
TI  - Expression of the proto-oncogene Ret, a component of the GDNF receptor complex,
      persists in human substantia nigra neurons in Parkinson's disease.
AB  - The proto-oncogene Ret, a membrane-associated receptor protein tyrosine kinase,
      has recently been shown to be a component of the glial cell line-derived
      neurotrophic factor (GDNF) receptor complex. GDNF has potent dopaminergic
      neurotrophic properties and has been suggested as a treatment for Parkinson's
      disease (PD). In this study, tissue sections of human substantia nigra (SN) from
      normal and PD cases were examined to determine the pattern of Ret expression in
      this region, and whether there was continued Ret expression in surviving
      dopaminergic neurons in PD cases. Using a polyclonal antibody to the amino
      terminal of Ret, immunoreactivity was localized in the SN to dopaminergic
      neurons. The antibody predominantly identified punctate deposits within cells. A
      similar pattern of immunoreactivity was observed in rat and monkey SN neurons. In
      neurologically normal cases, immunoreactivity was detected in many of the SN
      neurons. In all the PD cases studied, continued expression of Ret was observed in
      many of the surviving dopaminergic neurons. In certain cases, it was also
      detected on cells with the morphology of microglia. Ret expression by microglia
      was confirmed by immunoblot analysis on the human THP-1 macrophage type cell
      line. However, these cells did not express the mRNA for GDNFRalpha, the other
      component of the GDNF receptor complex.

PMID- 9593898
TI  - Glucocorticoids may alter antioxidant enzyme capacity in the brain: baseline
      studies.
AB  - Glucocorticoids (GCs), the adrenal steroids secreted during stress, have been
      shown to increase the vulnerability of hippocampal neurons to metabolic insults,
      potentially by altering the neuronal defense capacity against oxidative damage.
      These experiments assessed the effect of long term in vivo GC supplementation on
      basal activity of the antioxidant enzymes copper/zinc superoxide dismutase (Cu/Zn
      SOD), manganese superoxide dismutase (Mn SOD), catalase, and glutathione
      peroxidase (GSPx). Kinetic enzyme studies were done using brain tissue from the
      hippocampus, cortex, cerebellum, and also from liver as a peripheral control.
      Cu/Zn SOD activity was significantly lower in all brain regions of GC-treated
      rats, but higher in the liver. Mn SOD activity was unaffected by treatment.
      Catalase in the brain appeared largely unaffected by GC treatment, although liver
      catalase was significantly decreased. GSPx activity was significantly decreased
      by GCs at high peroxide levels in all tissues. These results indicate that the
      presence of GCs may lower the antioxidant capacity of tissues in a region
      specific manner, and that the deficit may not appear until the tissue is
      challenged with supranormal levels of oxidative products (as seen with GSPx).

PMID- 9593899
TI  - Glutamate neurotoxicity is associated with nitric oxide-mediated mitochondrial
      dysfunction and glutathione depletion.
AB  - The role of mitochondrial energy metabolism in glutamate mediated neurotoxicity
      was studied in rat neurones in primary culture. A brief (15 min) exposure of the
      neurones to glutamate caused a dose-dependent (0.01-1 mM) increase in cyclic GMP
      levels together with delayed (24 h) neurotoxicity and ATP depletion. These
      effects were prevented by either the nitric oxide (.NO) synthase (NOS) inhibitor
      Nomega-nitro-L-arginine methyl ester (NAME; 1 mM) or by the N-methyl-D-aspartate
      (NMDA) glutamate-subtype receptor antagonist D-(-)-2-amino-5-phosphonopentanoate
      (APV; 0.1 mM). Glutamate exposure (0.1 mM and 1 mM) followed by 24 h of
      incubation caused the inhibition of succinate-cytochrome c reductase (20-25%) and
      cytochrome c oxidase (31%) activities in the surviving neurones, without
      affecting NADH-coenzyme-Q1 reductase activity. The rate of oxygen consumption was
      impaired in neurones exposed to 1 mM glutamate, either with glucose (by 26%) or
      succinate (by 39%) as substrates. These effects on the mitochondrial respiratory
      chain and neuronal respiration, together with the observed glutathione depletion
      (20%) by glutamate exposure were completely prevented by NAME or APV. Our results
      suggest that mitochondrial dysfunction and impairment of antioxidant status may
      account for glutamate-mediated neurotoxicity via a mechanism involving .NO
      biosynthesis.

PMID- 9593900
TI  - Glucocorticoids may alter antioxidant enzyme capacity in the brain: kainic acid
      studies.
AB  - Glucocorticoids (GCs) predispose hippocampal neurons to damage during metabolic
      stressors. One component of hippocampal GC-endangerment may be changes in
      neuronal defenses against oxidative challenge. Previous experiments showed a
      decrease in basal levels of copper/zinc superoxide dismutase (Cu/Zn SOD) and
      glutathione peroxidase (GSPx) in the brain of rats treated with GCs [L. McIntosh,
      K. Hong, R. Sapolsky, Glucocorticoids may alter antioxidant enzyme capacity in
      the brain: baseline studies, 1997.]. In this study we administered the
      excitotoxin kainic acid (KA) to generate reactive oxygen species (ROS) in the
      brain, and monitored the activity of four antioxidant enzymes over 24 h in GC
      free and GC-supplemented rats. We tested the response pattern in three regions of
      the brain (hippocampus, cortex, cerebellum) and the liver as a peripheral
      control. In the hippocampus, KA induced Cu/Zn SOD and catalase, but GCs prevented
      the induction of catalase and maintained the lowered GSPx activity seen
      previously in the baseline studies. In the cortex, KA induced Cu/Zn SOD, Mn SOD
      and catalase activity, but there was no significant GC effect. There was no
      response to KA in the cerebellum, but GCs decreased GSPx activity. In the liver,
      KA produced a rise in Cu/Zn SOD and catalase activity, and GC-treated animals
      showed a slower return to baseline. These experiments indicate that the
      impairment of antioxidant enzyme defenses, particularly the hippocampal
      peroxidases, could be a component of GC-mediated neuroendangerment.

PMID- 9593901
TI  - 8-OH-DPAT influences extracellular levels of serotonin and dopamine in the medial
      preoptic area of male rats.
AB  - Serotonin (5-HT) is generally inhibitory to male rat sexual behavior. However,
      the 5-HT1A agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected either
      systemically or into the medial preoptic area (MPOA), facilitates ejaculation.
      Three experiments were conducted to test the effects of 8-OH-DPAT on 5-HT and
      dopamine (DA) neurotransmission in the MPOA, a very important site for the
      control of male sexual behavior. In Experiment 1, systemically injected 8-OH-DPAT
      (0.4 mg/kg) decreased extracellular 5-HT levels in the MPOA as measured by in
      vivo microdialysis. In Experiment 2, 8-OH-DPAT (500 microM) administered directly
      into the MPOA via reverse dialysis increased extracellular levels of both DA and
      5-HT; pretreatment with the selective 5-HT1A antagonist 4-iodo-N-[2-[4
      (methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-ben benzamide hydrochloride (p
      MPPI) failed to prevent 8-OH-DPAT's stimulatory effects on DA and 5-HT levels in
      the MPOA. In Experiment 3, 8-OH-DPAT (8 microg) co-injected with 5,7
      dihydroxytryptamine (5,7-DHT; 6 microg) prevented neurotoxic depletion of 5-HT in
      the site of injection (MPOA). Because systemic and MPOA injections of 8-OH-DPAT
      resulted in opposite effects on extracellular 5-HT in the MPOA, yet both can
      facilitate ejaculation, these data suggest that moderate changes in 5-HT in the
      MPOA may have relatively little influence on male copulatory behavior. Instead,
      the facilitative effects of 8-OH-DPAT in the MPOA on male copulatory behavior may
      result, at least in part, from stimulatory effects of 8-OH-DPAT on DA
      transmission. Facilitative effects of systemic injections of 8-OH-DPAT may result
      from decreased 5-HT release in several sites.

PMID- 9593902
TI  - Ginsenoside Rf, a trace component of ginseng root, produces antinociception in
      mice.
AB  - Ginseng root, a traditional oriental medicine, contains more than a dozen
      biologically active saponins called ginsenosides, including one present in only
      trace amounts called ginsenoside-Rf (Rf). Previously, we showed that Rf inhibits
      Ca2+ channels in mammalian sensory neurons through a mechanism requiring G
      proteins, whereas a variety of other ginsenosides were relatively ineffective.
      Since inhibition of Ca2+ channels in sensory neurons contributes to
      antinociception by opioids, we tested for analgesic actions of Rf. We find dose
      dependent antinociception by systemic administration of Rf in mice using two
      separate assays of tonic pain: in the acetic acid abdominal constriction test,
      the ED50 was 56+/-9 mg/kg, a concentration similar to those reported for aspirin
      and acetaminophen in the same assay; in the tonic phase of the biphasic formalin
      test, the ED50 was 129+/-32 mg/kg. Rf failed to affect nociception measured in
      three assays of acute pain: the acute phase of the formalin test, and the thermal
      (49 degrees C) tail-flick and increasing-temperature (3 degrees C/min) hot-plate
      tests. The simplest explanation is that Rf inhibits tonic pain without affecting
      acute pain, but other possibilities exist. Seeking a cellular explanation for the
      effect, we tested whether Rf suppresses Ca2+ channels on identified nociceptors.
      Inhibition was seen on large, but not small, nociceptors. This is inconsistent
      with a selective effect on tonic pain, so it seems unlikely that Ca2+ channel
      inhibition on primary sensory neurons can fully explain the behavioral
      antinociception we have demonstrated for Rf.

PMID- 9593903
TI  - Coordinate expression of L1 and 6B4 proteoglycan/phosphacan is correlated with
      the migration of mesencephalic dopaminergic neurons in mice.
AB  - Mesencephalic dopaminergic (DA) neurons of mice are generated from embryonic day
      10 to 12 (E10-12) in the ventricular zone of the mesencephalon. They first
      migrate toward the ventral mesencephalon, and then turn laterally, or
      tangentially, in the basal part of the mesencephalon. With immunohistochemical
      analysis of E10-E15 ICR mice, we found that cell adhesion molecule L1 was
      transiently expressed on the median part of tangential fibers coincident with the
      lateral migration of DA neurons from E11 to E13, when neurons move along the
      tangential fibers toward their final destinations: the reticular formation, the
      substantia nigra pars compact, and the ventral tegmental area. While L1
      expression was not observed in DA neurons, they expressed a chondroitin sulfate
      proteoglycan, 6B4 proteoglycan/phosphacan, which has been shown to bind to L1/Ng
      CAM in vitro. These results suggest that the heterophilic interaction between 6B4
      proteoglycan on the neurons and L1 on the fibers is involved in the lateral
      migration of mesencephalic DA neurons in mice.

PMID- 9593904
TI  - Inhibitors of NADH-ubiquinone reductase: an overview.
AB  - This article provides an updated overview of the plethora of complex I
      inhibitors. The inhibitors are presented within the broad categories of natural
      and commercial compounds and their potency is related to that of rotenone, the
      classical inhibitor of complex I. Among commercial products, particular attention
      is dedicated to inhibitors of pharmacological or toxicological relevance. The
      compounds that inhibit the NADH-ubiquinone reductase activity of complex I are
      classified according to three fundamental types of action on the basis of
      available evidence and recent insights: type A are antagonists of the ubiquinone
      substrate, type B displace the ubisemiquinone intermediate, and type C are
      antagonists of the ubiquinol product.

PMID- 9593905
TI  - Rat middle cerebral artery occlusion by an intraluminal thread compromises
      collateral blood flow.
AB  - We compared in Wistar rats collateral blood flow through leptomeningeal
      anastomoses after middle cerebral artery occlusion using craniotomy ('extravasal
      occlusion'), which results in a small volume of cerebral infarction, and after
      intraluminal thread occlusion ('intravasal occlusion'), which produces a large
      volume of cerebral infarction. Simultaneous laser-Doppler flowmetry with two
      probes placed on the cerebral cortex was used to measure and compare collateral
      blood flow. Extravasal occlusion caused a cortical blood flow reduction along a
      gradient in lateral direction, whereas blood flow reduction after intravasal
      occlusion was more uniformly distributed. It is concluded that permanent
      intravasal occlusion compromises collateral blood flow and therefore may not be a
      suitable model for measuring the ability of pharmacotherapeutic agents, if any,
      to improve collateral blood flow acutely after middle cerebral artery occlusion.
      The two models can be useful for testing drugs on parenchymal neuroprotective
      properties. Thereby, the intraluminal technique is preferred because of the
      possibility to study reperfusion damage when transient occlusion is applied.

PMID- 9593906
TI  - Responses of single lingual nerve fibers to thermal and chemical stimulation.
AB  - The goals of this study were to characterize the responses of: (1) thermally
      sensitive fibers of the lingual branch of the trigeminal nerve to cooling from 35
      degrees to 10 degrees C at a rate of 1 degrees C/s; and (2) these neurons to a
      mid-range concentration of NaCl (150 mM), glucose (150 mM), citric acid (0.3 mM),
      and quinine-HCl (3 mM) at 35 degrees and 25 degrees C. A cluster analysis of 47
      neurons' responses to cooling revealed two major groups and one minor group.
      Group 1 neurons (n=19) had a shorter latency, exhibited faster time-to-peak
      activity, and responded over a smaller range of temperature compared to Group 2
      neurons (n=22). Group 3 neurons (n=6) exhibited the longest response latency and
      responded over a wider cooler range of temperature. Twenty-five out of thirty-one
      thermally-sensitive, non-tactile lingual neurons responded weakly to at least one
      chemical stimulus, with some neurons responding to 2, 3, or all 4 chemical
      stimuli. Group 1 neurons responded to more chemical stimuli at 35 degrees C,
      while Group 2 neurons responded more at 25 degrees C. Under their optimal
      temperature conditions, Group 1 and Group 2 neurons responded most often to
      citric acid and least often to glucose, with NaCl and Q-HCl eliciting an
      intermediate number of responses. As a whole, the responses of thermally
      sensitive fibers to chemical stimulation were modest at best with an absence of
      chemical specificity. There was no evidence of a 'best' stimulus, although there
      was a suggestion of temporal coding.

PMID- 9593907
TI  - Specification of retinogeniculate X and Y axon arbors in cats: fundamental
      differences in developmental programs.
AB  - Monocular enucleation at E36, followed by intracellular labeling of single,
      physiologically identified X and Y axons, demonstrates fundamental differences in
      their termination patterns within the lateral geniculate nucleus (LGN). X axons
      have arbors that appear normal in their dorsoventral extent, though some are
      located in inappropriate regions of the LGN. Y axons have arbors that are either
      abnormally tall, spanning the entire extent of the LGN, or of normal height but
      located in inappropriate regions of the LGN. These termination patterns resemble
      patterns seen after monocular enucleation at E44, and reinforce the conclusion
      that X and Y axons differ fundamentally in the cues that constrain the
      dorsoventral extents of their arbors.

PMID- 9593908
TI  - Evidence that 5-HT3 receptors in the nucleus tractus solitarius and other
      brainstem areas modulate the vagal bradycardia evoked by activation of the von
      Bezold-Jarisch reflex in the anesthetized rat.
AB  - The effects of intracisternal (i.c.) application of the 5-HT3 receptor antagonist
      granisetron (0.016-0.16 microg kg-1) and the agonist phenylbiguanide (0.3-3
      microg kg-1) on reflex bradycardia evoked by injection of phenylbiguanide (i.v.;
      10 microg kg-1) were investigated in urethane anesthetized atenolol-pretreated
      rats. The effect of bilateral microinjection of granisetron (10 nmol per side,
      100 nl) into the nucleus tractus solitarius (NTS) on the reflex was also
      investigated. Intracisternal administration of granisetron dose-dependently
      (0.016-0.16 microg kg-1) and significantly attenuated the reflex bradycardia
      whilst the highest dose given i.v. had no significant effect on the reflex
      bradycardia. Phenylbiguanide given i.c. only caused significant potentiation at
      the middle dose (1 microg kg-1), having no significant effects at the other
      doses. Neither granisetron nor phenylbiguanide given i.c. affected resting heart
      rate or blood pressure. Granisetron microinjected bilaterally into the NTS also
      significantly attenuated both reflex bradycardia and hypotension. It is concluded
      that excitation of cardiac vagal motoneurones evoked by cardiopulmonary afferents
      involves activation of 5-HT3 receptors located in the nucleus tractus solitarius
      and other brainstem areas.

PMID- 9593909
TI  - Removal of the olfactory bulbs delays photic reentrainment of circadian activity
      rhythms and modifies the reproductive axis in male Octodon degus.
AB  - The diurnal rodent, Octodon degus, exhibits robust sex differences in several
      circadian measures, including circadian period (tau) and reentrainment rates to
      photic and nonphotic (social) zeitgebers. The neural substrates underlying such
      physiological differences remain unknown. In female degus, olfactory bulbectomies
      (BX) inhibit socially-facilitated reentrainment, but do not alter photic
      reentrainment, entrained measures, or tau in constant darkness (DD). This
      experiment investigated the effects of BX in male degus on (i) photic
      reentrainment rates of circadian rhythms following a 6-h phase advance of the
      light-dark (LD) cycle; (ii) photic entrainment; (iii) tau of free-running
      activity rhythms in DD; and (iv) body weight, paired testis weight, and the
      reproductive hormones, testosterone, androstenedione and follicle stimulating
      hormone (FSH). BX significantly delayed photic reentrainment rates. They did not,
      however, modify tau, the phase of activity onset or offset, amplitude or duration
      (alpha) of the activity rhythm, mean daily locomotor activity levels, or body
      weight. FSH, testosterone and androstenedione were unaffected by BX, whereas
      paired testis weights were significantly greater in BX degus compared with shams.
      Thus, the olfactory bulbs influence photic reentrainment of circadian rhythms and
      modestly affect the reproductive axis in male degus. Our results suggest that the
      olfactory bulbs may be a neural source of observed sex differences in photic
      reentrainment in degus, and highlight interspecies variation in the olfactory
      bulbs' effects on entrained and free-running circadian rhythms and on
      reproduction.

PMID- 9593910
TI  - The gonadotropin-releasing hormone system does not develop in Small-Eye (Sey)
      mouse phenotype.
AB  - This study examined the development of the gonadotropin releasing-hormone (GnRH)
      system in a spontaneous mouse mutation, Small-Eye (Sey). This phenotype is due to
      a point mutation in the developmental control gene Pax-6 and results in failed
      development of the eye and olfactory placodes in homozygous (Sey/Sey) embryos and
      a variety of eye abnormalities in heterozygotes (Sey/+). Therefore, Sey/Sey
      embryos provided a naturally occurring olfactory placode ablation to ask whether
      all of the GnRH neurons found in the adult mouse forebrain arise from the
      olfactory epithelium. In Sey/Sey embryos, GnRH-immunoreactive neurons were not
      present in either the presumptive nasal regions or in any area of the brain at
      any embryonic age. In contrast, in Sey/+ embryos, there was no apparent effect on
      either GnRH cell proliferation or migration. These data support and extend the
      hypothesis that GnRH neurons in mice originate in the olfactory placodes and also
      demonstrate that two normal alleles of Pax-6 are not required for GnRH system
      development.

PMID- 9593911
TI  - Regeneration of ascending spinal axons in goldfish.
AB  - Regeneration of descending spinal cord tracts occur spontaneously in adult
      goldfish. Very little information is available regarding the fate of ascending
      fibers. Using Dextran amines as a tracer, we studied the normal and regenerated
      ascending axonal projection patterns in adult goldfish brain nuclei. Present
      study includes spinal projections to torus semicircularis, hypothalamus, thalamus
      and the telencephalon. Regenerated fibers had finer caliber axons and the
      terminal axonal arbors covered a larger area than the corresponding normal ones.

PMID- 9593912
TI  - Central executive function in working memory: event-related brain potential
      studies.
AB  - Visual event-related brain potentials (ERPs) were recorded during a running
      memory task, in which subjects dynamically revised (updated) memory stores, and a
      control task not requiring maintenance of a changing memory set but utilising
      identical stimulus sequences and response patterns. In three experiments, ERPs
      associated with cognitive processes were isolated through subtraction of control
      potentials from ERPs acquired during updating. We provide evidence that resultant
      difference ERPs primarily reflected processing or processing control, as opposed
      to storage. These findings are consistent both with Baddeley's working memory
      model, which postulates separate storage and control modules, and Morris and
      Jones' behavioral evidence for specific involvement of Baddeley's central
      executive in memory updating. In addition, our ERP data indicate that updating
      requires processes not suggested by Morris and Jones' behavioural studies;
      possibly control processes engaged to reduce the effects of proactive
      interference. Overall the data are consistent with the discovery of an ERP
      correlate of central executive activity.

PMID- 9593914
TI  - Structure-activity relationships of some complex I inhibitors.
AB  - A wide variety of complex I inhibitors act at or close to the ubiquinone
      reduction site. Identification of the structural factors required for exhibiting
      inhibitory actions on the basis of structure-activity relationships is useful to
      elucidate the manner in which inhibitors interact with the enzyme. This review
      summarizes studies on the structure-activity relationship of rotenoids,
      piericidins, capsaicins, pyridinium-type inhibitors and modern synthetic
      agrochemicals acting at mitochondrial complex I.

PMID- 9593915
TI  - Food restriction attenuates the blood pressure response to paraventricular
      hypothalamic nuclei lesions in aortic coarctation hypertension.
AB  - Chronic food restriction reduces blood pressure (BP) and sympathetic support of
      BP in aortic coarctation hypertension. The purpose of this study was to test the
      hypothesis that chronic food restriction would reduce sympathetic support of BP
      mediated by the paraventricular hypothalamic nuclei (PVN). Hypertension was
      induced in male Sprague-Dawley rats (n=40) by suprarenal aortic coarctation. Rats
      were assigned to either an ad libitum fed (AL) group or a food restricted (FR)
      group that received 60% of the food consumed by AL for 3 weeks. One week prior to
      data collection, catheters were implanted in the left carotid artery and right
      jugular vein. BP was measured for 2 days prior to, and 7 days after rats in AL
      and FR groups received either bilateral electrolytic lesions of the PVN (PVNx) or
      sham lesions (SHAM). Prior to either PVNx or SHAM, FR rats had significantly
      lower BP (AL=152+/-5; FR=113+/-2 mmHg), less of a depressor response to
      ganglionic blockade (AL=-58+/-4; FR=-35+/-2 mmHg), and lower plasma
      norepinephrine levels (AL=758+/-71; FR=380+/-23 pg/ml) compared to AL. PVNx
      reduced BP in both AL and FR rats (AL-PVNx=105+/-6 mmHg, FR-PVNx=101+/-3 mmHg).
      PVNx also lowered the depressor response to ganglionic blockade (AL-PVNx=-28+/-5
      mmHg, FR-PVNx=-29+/-4 mmHg) and plasma norepinephrine levels (AL-PVNx=372+/-74
      pg/ml, FR-PVNx=248+/-31 pg/ml). FR decreased the magnitude of the reductions in
      resting BP and in sympathetic activity in response to PVNx. These results
      indicate that intact PVN are required for maintenance of aortic coarctation
      hypertension, and implicate the PVN as a site involved in BP reductions produced
      by chronic food restriction.

PMID- 9593913
TI  - Morphine and anandamide coupling to nitric oxide stimulates GnRH and CRF release
      from rat median eminence: neurovascular regulation.
AB  - Nitric oxide (NO) is involved in neurohormonal secretion from median eminence
      neuroendocrine nerve terminals. We report that stimulation of NO release from
      median eminence fragments including vascular tissues occurs by mu3 receptor
      activation by morphine, or by cannabinoid type 1 receptor activation by
      anandamide. The released levels of NO are lower after anandamide than after
      morphine stimulation. These processes can be blocked by L-NAME, a specific nitric
      oxide synthase inhibitor, by naloxone for the morphine-stimulated NO release, or
      SR 141716A, a specific CB1 receptor inhibitor, for the anandamide-stimulated NO
      release. Furthermore, morphine and anandamide, by this NO dependent process,
      influences neurohormonal release from median eminence nerve terminals within 10
      min. Via this NO dependent process, morphine stimulates both GnRH and CRF
      release, whereas anandamide selectively stimulates GnRH release. These
      observations together with previous data suggest that morphine and the anandamide
      stimulated NO originates from the vascular endothelium of the portal plexus.
      These results indicate that endothelial cells of the median eminence may be
      involved in the release of neurohormones.

PMID- 9593916
TI  - Differential expression of monoamine oxidase A, serotonin transporter, tyrosine
      hydroxylase and norepinephrine transporter mRNA by anorexia mutation and food
      deprivation.
AB  - The Anorexia (anx) mutation causes reduced food intake in preweanling mice,
      resulting in death from starvation within 3-4 weeks. We have found serotonin
      (5HT) hyperinnervation in the anx brain; altered noradrenergic (NE) innervation
      may also mediate eating disorders. We examined the expression of synthetic or
      catabolic monoamine enzyme genes in brainstem nuclei: serotonin transporter
      (5HTT) and monoamine oxidase A (MAOA) in the raphe nuclei (RN), and MAOA,
      norepinephrine transporter (NET), and tyrosine hydroxylase (TH) in the locus
      ceruleus (LC). We compared 3-week old anx with control and 24-h food-deprived
      wildtype littermates using in situ hybridization to measure mRNA levels by
      quantitative autoradiography. The anx mutation was correlated with decreased MAOA
      mRNA in the LC (but not RN), decreased 5HTT mRNA in the RN, and a trend towards
      lower NET mRNA in the LC. Food deprivation decreased MAOA mRNA in the LC (but not
      RN), increased TH mRNA in the LC, and did not alter NET or 5HTT mRNA levels.
      Thus, the effect of the anx mutation on MAOA expression in the LC paralleled the
      effect of food-deprivation, but the anx mutation and food-deprivation had
      differential effects on the expression of TH, NET, and 5HTT genes. Decreased 5HTT
      expression in the anx RN is consistent with upregulation of serotonergic
      neurotransmission that may accompany 5HT hyperinnervation. Central NE levels or
      innervation may be altered in anx mice by decreased expression of NET and MAOA
      and a lack of TH upregulation induced by food deprivation as in wild-type mice.

PMID- 9593917
TI  - A reductant-induced oxidation mechanism for complex I.
AB  - A model for energy conversion in Complex I is proposed that is a conservative
      expansion of Mitchell's Q-cycle using a simple mechanistic variation of that
      already established experimentally for Complex III. The model accommodates the
      following proposals. (1) The large number of flavin and iron-sulfur redox
      cofactors integral to Complex I form a simple but long electron transfer chain
      guiding submillisecond electron transfer from substrate NADH in the matrix to the
      [4Fe-4S] cluster N2 close to the matrix-membrane interface. (2) The reduced N2
      cluster injects a single electron into a ubiquinone (Q) drawn from the membrane
      pool into a nearby Qnz site, generating an unstable transition state semiquinone
      (SQ). The generation of a SQ species is the primary step in the energy conversion
      process in Complex I, as in Complex III. In Complex III, the SQ at the Qo site
      near the cytosolic side acts as a strong reductant to drive electronic charge
      across the membrane profile via two hemes B to a Qi site near the matrix side. We
      propose that in Complex I, the SQ at the Qnz site near the matrix side acts as a
      strong oxidant to pull electronic charge across the membrane profile via a
      quinone (Qny site) from a Qnx site near the cytosolic side. The opposing
      locations of matrix side Qnz and cytosolic side Qo, together with the opposite
      action of Qnz as an oxidant rather than a reductant, renders the Complex I and
      III processes vectorially and energetically complementary. The redox properties
      of the Qnz and Qo site occupants can be identical. (3) The intervening Qny site
      of Complex I acts as a proton pumping element (akin to the proton pump of Complex
      IV), rather than the simple electron guiding hemes B of Complex III. Thus the
      transmembrane action of Complex I doubles to four (or more) the number of protons
      and charges translocated per NADH oxidized and Q reduced. The Qny site does not
      exchange with the pool and may even be covalently bound. (4) The Qnx site on the
      cytosol side of Complex I is complementary to the Qi site on the matrix side of
      Complex III and can have the same redox properties. The Qnx site draws QH2 from
      the membrane pool to be oxidized in two single electron steps. Besides explaining
      earlier observations and making testable predictions, this Complex I model re
      establishes a uniformity in the mechanisms of respiratory energy conversion by
      using engineering principles common to Complexes III and IV: (1) all the primary
      energy coupling reactions in the different complexes use oxygen chemistry in the
      guise of dioxygen or ubiquinone, (2) these reactions are highly localized
      structurally, utilizing closely placed catalytic redox cofactors, (3) these
      reactions are also highly localized energetically, since virtually all the free
      energy defined by substrates is conserved in the form of transition state that
      initiates the transmembrane action and (4) all complexes possess apparently
      supernumerary oxidation-reduction cofactors which form classical electron
      transfer chains that operate with high directional specificity to guide electron
      at near zero free energies to and from the sites of localized coupling.

PMID- 9593918
TI  - Calpain-mediated regulation of NMDA receptor structure and function.
AB  - Calpains have been previously shown to regulate AMPA receptor properties by
      producing partial truncation of the C-terminal domains of several receptor
      subunits. We now report that NMDA receptor subunits, in particular NR2 subunits,
      are also subjected to calpain-mediated truncation. Treatment of synaptic
      membranes with calpain I resulted in truncation of both NR1 and NR2 subunits,
      with the appearance of NR2 species with lower mol.wt. than native subunits, but
      still recognized by antibodies directed at the C-terminal domain. This treatment
      did not modify the binding of several ligands of the NMDA receptors, such as
      glutamate, glycine or TCP. Incubation of thin frozen-thawed brain sections with
      calcium resulted in calpain-mediated selective degradation of NR2 subunits, as
      truncation into smaller fragments was totally blocked by calpain inhibitors.
      Under the same conditions, TCP binding to sections was decreased by about 50%, an
      effect also blocked by calpain inhibitors. Treatment of hippocampal slices in
      culture with the excitotoxin, kainic acid, also produced calpain-mediated
      truncation of the C-terminal domain of NR2 but not NR1 subunits of the NMDA
      receptors. The results indicate that calpain activation produces several
      modifications of NMDA receptors, including the truncation of the C-terminal
      domain of NR2 subunits, and changes in channel binding properties. They suggest
      that calpain-mediated regulation of NMDA receptors might represent a feed-back
      regulation of the receptors which could be used to limit receptor activation.

PMID- 9593919
TI  - Age-related decline in striatal dopamine release and motoric function in brown
      Norway/Fischer 344 hybrid rats.
AB  - The Brown Norway/Fischer 344 F1 hybrid rats (F344BNF1) is a newer rat model and
      is emerging as an important rodent model of aging. In the present study we used
      motoric performance tests, intracerebral microdialysis, and neurochemical
      measures of postmortem brain tissue to investigate the effects of aging in young
      (4-5 months), middle-aged (18-19), and old (24-25 months) F344BNF1 hybrid rats.
      We observed that old F344BNF1 rats exhibited decreased motoric performance, and
      lower levels of spontaneous and d-amphetamine-induced locomotor activity than
      those observed in young F344BNF1 rats. Microdialysis measures of extracellular
      basal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4
      hydroxy-3-methoxyphenylacetic acid (HVA) were significantly diminished in the
      striata of the middle-aged and old rats as compared to levels in young animals.
      In addition, d-amphetamine-evoked overflow of DA was significantly decreased in
      the middle-aged and aged rat striatum as compared to DA overflow in young
      F344BNF1 rats. Studies of postmortem brain tissue showed that the changes in
      overflow of DA correlated with significantly lower DA tissue content in ventral
      striatum and midbrain. Moreover, both dopamine turnover ratios (DOPAC/DA, HVA/DA)
      and the serotonin turnover ratio (5-HIAA/5-HT) were significantly elevated in the
      ventral striatum and nucleus accumbens. The results of this study demonstrate a
      correlation between reductions in striatal DA neurochemistry and diminished motor
      function in aged F344BNF1 rats.

PMID- 9593920
TI  - Evidence for additional neurotensin receptor subtypes: neurotensin analogs that
      distinguish between neurotensin-mediated hypothermia and antinociception.
AB  - Neurotensin (NT), a tridecapeptide, is a neurotransmitter that elicits potent
      effects including hypothermia and antinociception in mice and rats. To date,
      there are two types of the neurotensin receptor (NTR) that have been molecularly
      cloned from the rat. However, several lines of evidence suggest the presence of
      additional NTR subtypes. We have identified a NT analog of the NT(8-13) fragment,
      NT27, that selectively causes only the hypothermic response in vivo, when
      microinjected into the periaqueductal gray (PAG) of rats. A dose of 18 nmol of NT
      or NT27 caused a body temperature lowering of 1.8 and 1.2 degrees C,
      respectively. This same dose of NT or NT27 yielded a hotplate maximum
      physiological effect of 75% and 25%, respectively. Interestingly, despite its
      high KD (620 nM) at the cloned NTR-1, NT27-I (the iodinated form of NT27) exerted
      a potent hypothermic effect even at a very low dose (0.6 nmol). Equally
      intriguing, was that NT24, a sterioisomer of NT27, with a much higher affinity
      (KD=0. 5 nM) at NTR-1, did not selectively induce hypothermia in mice, but did
      selectively induce hypothermia in rats.

PMID- 9593921
TI  - Developmental expression of messenger RNA levels of the alpha subunit of the GTP
      binding protein, Gz, in the mouse nervous system.
AB  - There has been recent evidence that Gz may play a role in the transmission of the
      neurotrophic signal from nerve terminals to the cell bodies [Johanson, S.O.,
      Crouch, M.F., Hendry, I.A., Signal transduction from membrane to nucleus: the
      special case for neurons, Neurochem. Res. 21 (1996) 779-785]. We examined the
      developmental expression of the alpha subunit of Gz (Gzalpha) in the peripheral
      and central nervous systems of the mouse. Our laboratory has developed a
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) for Gzalpha
      which makes use of a fragment of the PCR product shortened by 107 base pairs
      creating a standard which mimics the original RNA. Serial dilutions of the mouse
      RNA with a constant concentration of mimic RNA were made and the point where
      equal amounts of product are formed allows accurate measurement of Gzalpha mRNA
      in the tissue. We have demonstrated that in the developing mouse superior
      cervical ganglion (SCG), dorsal root ganglion (DRG) and trigeminal ganglion the
      expression of Gzalpha mRNA is highest perinatally. From 3 weeks of age, in all
      tissues with the exception of the SCG, Gzalpha mRNA levels fall to lower levels
      in the adult animal. The developmental pattern of expression of Gzalpha in both
      the cerebellum and the brain differs from the peripheral nervous system. In the
      cerebellum, Gzalpha mRNA expression is highest around birth and in the brain it
      is highest around third postnatal week and then the levels decline as adulthood
      is approached. These results suggest that the highest level of Gzalpha mRNA is
      expressed at the time when target tissue innervation is occurring. This further
      strengthens the hypothesis that Gzalpha is important in the transfer of
      information from target tissues to the innervating nerve cells.

PMID- 9593922
TI  - Effects of spatial selective attention on the steady-state visual evoked
      potential in the 20-28 Hz range.
AB  - Steady-state visual evoked potentials (SSVEPs) were recorded from the scalp of
      subjects who attended to a flickering LED display in one visual field while
      ignoring a similar display (flickering at a different frequency) in the opposite
      visual field. The flicker frequencies were 20.8 Hz in the left-field display and
      27.8 Hz in the right-field display. The SSVEP to the flicker in either field was
      enhanced in amplitude when attention was directed to its location. The scalp
      distribution of this SSVEP enhancement was narrowly focused over the posterior
      scalp contralateral to the visual field of stimulation. A source analysis using
      Variable Resolution Electromagnetic Tomography (VARETA) indicated that the source
      current densities for the SSVEP attention effect had a focal origin in the
      contralateral parieto-occipital cortex.

PMID- 9593923
TI  - Lack of autoreceptor-mediated inhibitory control of dopamine release in striatal
      synaptosomes of D2 receptor-deficient mice.
AB  - Mouse purified striatal synaptosomes were used to study the release of newly
      synthesised [3H]-dopamine ([3H]-DA) or of previously taken up [3H]-DA. Quinpirole
      (QP, 10 microM), a D2/D3 dopaminergic agonist, was found to reduce the release of
      newly synthesised [3H]-DA with a larger amplitude when 4-aminopyridine (100
      microM) instead than veratridine (1 microM) or potassium (25 mM) was used to
      evoke DA release. Among the different D2/D3 dopaminergic agonists tested R(-)
      propylnorapomorphine (NPA) and quinpirole were the most potent. These compounds
      reduced, in a concentration-dependent manner, the 4-aminopyridine-evoked release
      of [3H]-DA previously taken up by synaptosomes (50% maximal inhibition). In
      contrast, the D3 agonist PD-128,907 had little effect even when used at 100 nM.
      The QP (100 nM)-induced response was completely antagonised by sulpiride (1
      microM). Strikingly, the NPA (100 nM) and PD-128,907 (100 nM)-evoked responses
      were completely suppressed in D2 receptor-deficient mice. This data strongly
      suggest that only D2 but not D3 receptors are involved in the autoreceptor
      mediated inhibition of the evoked release of [3H]-DA. Interestingly, while
      amphetamine-induced release of [3H]-DA was not modified, a slight reduction of
      [3H]-DA efflux induced by the dopamine (DA) uptake inhibitor cocaine was observed
      in D2 receptor-deficient mice.

PMID- 9593924
TI  - Lordosis-enhancing medial preoptic area lesions do not alter hypothalamic
      estrogen receptor- or progestin receptor-immunoreactivity in prepubertal female
      guinea pigs.
AB  - Female guinea pigs rarely display adult-typical lordosis responses to ovarian
      steroid hormones until 40-50 days of age. Behavioral hyporesponsiveness in
      prepubertal females may be due, in part, to deficiencies in hypothalamic estrogen
      receptors and/or estradiol-induced progestin receptors. This study was designed
      to test the hypothesis that bilateral medial preoptic area (MPOA) lesions, which
      enhance the display of progesterone-facilitated lordosis in juvenile females,
      increase levels of hypothalamic estrogen receptors and/or estradiol-induced
      progestin receptors. Hartley guinea pigs were ovariectomized at 11-12 days of age
      and at 14-15 days of age received bilateral electrolytic or sham lesions aimed at
      the MPOA. At approximately 3 weeks of age, lesioned and sham-lesioned animals
      were either tested for the display of progesterone-facilitated lordosis or
      perfused, and their hypothalamic tissue processed for estrogen receptor- or
      estradiol-induced progestin receptor-immunostaining. Although a significantly
      higher percentage of MPOA-lesioned than sham-lesioned guinea pigs displayed
      progesterone-facilitated lordosis (85.7% vs. 5. 8%, respectively, p<0.05), there
      were no significant lesion-related differences in the number or staining
      intensity of cells containing estrogen receptor- or estradiol-induced progestin
      receptor-immunoreactivity in the ventrolateral hypothalamus or arcuate nucleus.
      These data do not support the hypothesis that the enhanced display of
      progesterone-facilitated lordosis in prepubertal guinea pigs following MPOA
      lesions is due to increased hypothalamic concentrations of estrogen receptors or
      estradiol-induced progestin receptors.

PMID- 9593926
TI  - Antagonism between the suppressive effects of NH3 and CO2 on bullfrog taste nerve
      responses to quinine.
AB  - The suppression mechanism of NH3 and CO2 on bullfrog taste nerve responses to 0.1
      mM quinine was investigated by applying them directly on the tongue surface
      (surface application) or at the tongue interstices through the lingual artery
      (interstitial application). The surface application of NH3 and CO2 reversibly
      suppressed the taste nerve responses with IC50 values of 0.37 mM and 2.2 mM,
      respectively, whereas their hydrates were ineffective. The interstitial
      application of NH3 reversibly suppressed the taste nerve responses. The surface
      application of CO2 recovered the suppressed responses to quinine. The 4 s
      application of CO2 prior to that of 0.1 mM quinine had the maximum effect. These
      results show that NH3-induced alkalosis and CO2-induced acidosis of taste cells,
      taste nerve endings, or tongue interstices surrounding them suppressed the taste
      nerve responses, and that the neutralization of their intracellular pH recovered
      these responses. The time-dependent recovery suggests that the neutralization at
      a layer inside taste cells, taste nerve endings, or the interstices surrounding
      them is critical in taste transduction.

PMID- 9593925
TI  - Alterations in GLUT1 and GLUT3 glucose transporter gene expression following
      unilateral hypoxia-ischemia in the immature rat brain.
AB  - The brain damage produced by unilateral cerebral hypoxia-ischemia in the immature
      rat results from major alterations in cerebral energy metabolism and glucose
      utilization which begin during the course of the insult and proceed into the
      recovery period. Consistent with a lack of pathology, the alterations in the
      hemisphere contralateral to the carotid artery ligation are transient and return
      to normal within 24 h of recovery, whereas the hemisphere ipsilateral to the
      ligation exhibits both early and late responses, and infarction. The facilitative
      glucose transporter proteins mediate glucose transport across the blood-brain
      barrier (55 kDa GLUT1), and into neurons and glia (GLUT3 and 45 kDa GLUT1), and
      demonstrate both early and late responses to perinatal hypoxia-ischemia. This
      study employed in situ hybridization histochemistry to investigate the temporal
      and regional patterns of GLUT1 and GLUT3 gene expression following a severe (2.5
      h) hypoxic-ischemic insult in the 7-day old rat brain. Enhanced GLUT1 mRNA
      expression was apparent in cerebral microvessels of both hemispheres and remained
      elevated in the ipsilateral hemisphere through 24 h of recovery, consistent with
      our previous observation of increased microvascular 55 kDa GLUT1 protein. The
      expression of the neuronal isoform, GLUT3, was enhanced in penumbral regions,
      such as piriform cortex and amygdala, but was rapidly reduced in the affected
      areas of cortex, hippocampus and thalamus, reflecting necrosis. The late
      response, observed at 72 h of recovery, was characterized by extensive necrosis
      in the ipsilateral hemisphere, loss of GLUT3 expression, and a gliotic reaction
      including increased GLUT1 in GFAP-positive astrocytes. This study demonstrates
      that cerebral hypoxia-ischemia in the immature rat produces both immediate-early
      and long-term effects on the glucose transporter proteins at the level of gene
      expression.

PMID- 9593927
TI  - Human complex I defects in neurodegenerative diseases.
AB  - Complex I deficiency, either specific or associated with other respiratory chain
      defects, has been identified in myopathies, encephalomyopathies and in three
      'neurodegenerative' disorders: Parkinson's disease, dystonia and Leber's
      hereditary optic neuropathy. The complex I defect is expressed in blood in all
      these three but, to date, only in LHON have specific mitochondrial DNA mutations
      been identified. Recent work with rho degrees cybrids indicates that, in a
      subgroup of patients at least, the complex I deficiency is determined by mtDNA,
      in contrast to dystonia where a nuclear gene defect or toxic influence appears a
      more likely cause. The actions of specific toxins, e.g., MPTP continue to play an
      important role in our understanding of pathogenesis of neurodegeneration,
      particularly in PD.

PMID- 9593928
TI  - Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to
      the cGMP-mediated pathway in the rat neuropathic pain model.
AB  - Intrathecal injection of a nitric oxide releasing compound, NOC-18, was used to
      define the role of nitric oxide (NO) in the spinal mechanism of neuropathic pain
      caused by unilateral chronic constriction injury to rat sciatic nerves. Paw
      withdrawal latency was used to evaluate nociception induced by thermal stimuli
      before surgery and afterwards at 1, 3, and 6 h, and on days 1, 2, 3, 4, 5, 8, and
      12 after the nerve ligature. In the sham-surgery control groups, intrathecal
      injection of 10 or 100 microg of NOC-18 did not produce any change in withdrawal
      latencies. In rats with unilateral nerve ligation, however, administration of 1
      or 10 microg, but not 0.1 microg, of NOC-18 significantly shortened the time in
      which thermal hyperalgesia developed after nerve injury. Injection of 1 microg of
      NOC-18 decreased the onset time of thermal hyperalgesia from 2 days to 3 h and
      with 10 microg hyperalgesia developed within 1 h after the nerve injury. The
      effects of intrathecal injection of MK-801, a N-methyl-D-aspartate (NMDA)
      receptor antagonist, N-nitro-L-arginine methyl ester (L-NAME), a NO synthase
      inhibitor, methylene blue (MB), a soluble guanylate cyclase inhibitor, and
      hemoglobin (Hb), a NO scavenger, on the development of thermal hyperalgesia after
      the sciatic nerve ligature were examined in the presence and absence of 1 and 10
      microg of NOC-18. Acceleration of the development of thermal hyperalgesia induced
      by 1 and 10 microg NOC-18 was completely inhibited by Hb, but was not affected by
      either MK-801, L-NAME or MB. These findings indicate that NO plays an important
      role in the rapid development of thermal hyperalgesia after the nerve injury, but
      that facilitation of nociceptive processing in the spinal cord may entail an
      alternate to the NO-cyclic guanosine 3',5'-monophosphate (cGMP) pathway.

PMID- 9593929
TI  - Neuropeptide immunoreactivity in ligature-induced neuromas of the inferior
      alveolar nerve in the ferret.
AB  - Injury to branches of the trigeminal nerve can sometimes result in persistent
      dysaesthesia. In an attempt to understand the aetiology of this condition we are
      currently investigating changes which occur at the injury site. In the present
      study we have examined the expression of seven neuropeptides, all of which have
      been implicated in nociceptive transmission, or have previously been shown to
      have altered expression following nerve injury. In 20 adult ferrets the inferior
      alveolar nerve was sectioned and ligated, and recovery permitted for 3 days, 8
      days, 3 weeks, 6 weeks or 12 weeks. Longitudinal sections of the neuromas were
      processed using immunohistochemical techniques to quantify the expression of
      substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide,
      galanin, somatostatin, enkephalin and neuropeptide Y. After 3 days, all of the
      neuropeptides were expressed at the injury site. In the neuromas examined after
      longer recovery periods these levels of expression had declined and were similar
      to those found in the contralateral controls. This initial high level, followed
      by a decline, parallels the incidence of ectopic neural activity recorded
      electrophysiologically in the same model. It is, therefore, possible that the
      accumulation of neuropeptides at the injury site may play a role in the
      initiation or modulation of ectopic neural activity.

PMID- 9593930
TI  - First- and second-order motion perception in Gabor micropattern stimuli:
      psychophysics and computational modelling.
AB  - This paper examines the perception of first- and second-order motion in human
      vision. In an extension of previous work by Boulton and Baker [J.B. Boulton, C.L.
      Baker, Motion detection is dependent on spatial frequency not size, Vision Res.,
      31 (1991) 77-87; J.B. Boulton, C.L. Baker, Different parameters control motion
      perception above and below a critical density, Vision Res., 33 (1993) 1803-1811],
      the direction of two-frame apparent motion is measured for stimuli composed of
      Gabor or Gaussian micropatterns. Three conditions are investigated. Condition 1
      is that used by Boulton and Baker, in which motion is defined by the displacement
      of Gabor micropatterns. In condition 2, motion is defined by the displacement of
      Gaussian micropatterns. In condition 3, the envelopes of Gabor micropatterns are
      displaced while their carriers remain static. Using sparsely distributed
      micropatterns, direction judgements in all three conditions are determined by the
      spacing of the micropatterns. With a dense stimulus, direction judgements vary as
      a function of displacement in qualitatively different ways for the three
      conditions. The psychophysical results are predicted by a two-channel
      computational model. In one channel, motion is calculated directly from stimulus
      luminance, while in the other it is preceded by a texture-grabbing operation. The
      relative activities of the two channels dictates which governs direction
      judgements for any given stimulus.

PMID- 9593931
TI  - Lowering ambient or core body temperature elevates striatal MPP+ levels and
      enhances toxicity to dopamine neurons in MPTP-treated mice.
AB  - The neuroprotective effects of lowering body temperature have been well
      documented in various models of neuronal injury. The present study investigated
      the effects a lower ambient or core body temperature would have on damage to
      striatal dopamine (DA) neurons produced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). Mice received systemic MPTP treatment at two different
      temperatures, 4 degrees C and 22 degrees C. MPTP-treated mice maintained at 4
      degrees C demonstrated (1) a greater hypothermic response, (2) a significant
      reduction in striatal DA content and tyrosine hydroxylase (TH) activity, and (3)
      significantly greater striatal 1-methyl-4-phenylpyridinium (MPP+) levels, as
      compared to mice dosed with MPTP at room temperature. Parallel studies with
      methamphetamine (METH) were conducted since temperature appears to play a pivotal
      role in the mediation of damage to DA neurons by this CNS stimulant in rodents.
      As previously reported, METH-induced hyperthermia and the subsequent loss of
      striatal DA content were attenuated in animals dosed at 4 degrees C. We also
      evaluated the effects a hypothermic state induced by pharmacological agents would
      have on striatal neurochemistry and MPP+ levels following MPTP treatment.
      Concurrent administration of MK-801 or 8-OHDPAT increased the striatal MPP+
      levels following MPTP treatment. However, only 8-OHDPAT potentiated the MPTP
      induced decrements of striatal DA content and TH activity; MK-801 did not affect
      MPTP decreases in these striatal markers of dopaminergic damage. Altogether,
      these findings indicate that temperature has a profound effect on striatal MPP+
      levels and MPTP-induced damage to DA neurons in mice.

PMID- 9593932
TI  - Effects of anoxic stress on prostaglandin H synthase isoforms in piglet brain.
AB  - We examined effects of ischemia and asphyxia on levels of prostaglandin H
      synthase-1 (PGHS-1) and prostaglandin H synthase-2 (PGHS-2) in piglet brain.
      Ischemia was induced by increasing intracranial pressure and asphyxia was induced
      by turning off the respirator. Duration of anoxic stress was 10 min. In some
      animals, indomethacin (5 mg/kg, i.v.) or 7-nitroindazole (7-NI) was administered
      prior to ischemia to block PGHS or brain nitric oxide synthase (bNOS),
      respectively. Tissues from cerebral cortex and hippocampus were removed and fixed
      and/or frozen after 1, 2, 4 and 8 h of recovery from anoxic stress. In addition,
      tissues were obtained from untreated animals or from time control animals. Levels
      of mRNA and proteins were determined using RNase protection assay and
      immunohistochemical approaches, respectively. In the tissues studied, only a few
      neurons were immunopositive for PGHS-1, and neither ischemia or asphyxia affected
      PGHS-1 immunostaining at 8 h after recovery. Likewise, PGHS-1 mRNA did not
      increase following anoxic stress. In contrast, substantial PGHS-2
      immunoreactivity was present in neurons and glial cells in the cerebral cortex
      and hippocampus and there was no difference between time control and non treated
      animals. PGHS-2 mRNA increased by 2-4 h after ischemia, and heightened
      immunoreactivity for PGHS-2 was present at 8 h after ischemia in cerebral cortex
      and hippocampus. However, asphyxia did not increase PGHS-2 mRNA or
      immunostaining. Indomethacin pretreatment inhibited increases in mRNA and protein
      for PGHS-2 after ischemia, while 7-NI had little effect on increases in PGHS-2
      immunoreactivity. We conclude that: (1) PGHS-2 is the predominant isoform present
      in piglet cerebral cortex and hippocampus; (2) Ischemia but not asphyxia
      increases levels of PGHS-2; (3) Ischemia does not increase levels of PGHS-1; and
      (4) Indomethacin but not 7-NI attenuates ischemia-induced increases in PGHS-2.

PMID- 9593933
TI  - Regionally specific induction of BDNF and truncated trkB.T1 receptors in the
      hippocampal formation after intraseptal injection of kainic acid.
AB  - The septo-hippocampal cholinergic and GABAergic systems were lesioned with single
      unilateral injections of kainic acid (KA) into the septum to further characterize
      the role of these afferents in the regulation of hippocampal brain-derived
      neurotrophic factor (BDNF) expression. Nearly all cells expressing choline
      acetyltransferase, trkA or glutamic acid decarboxylase mRNA disappeared in the
      medial septum 7 days after the neurotoxin administration. The lesion resulted in
      a complete loss of CA3 pyramidal cells, and robust increases in BDNF mRNA levels
      in hippocampal granular dentate cells and in the amygdala. There were rapid
      transient increases of BDNF mRNA levels in the hippocampal formation and cortex.
      In addition, we found a strong induction of truncated trkB.T1 mRNA receptors in
      the stratum radiatum and stratum oriens of the CA3 subfield. The prolonged
      induction of BDNF mRNA levels suggests an important role of this neurotrophin,
      possibly mediated by truncated trkB receptors, in the regulation of hippocampal
      plasticity following injury.

PMID- 9593934
TI  - Human complex I deficiency: clinical spectrum and involvement of oxygen free
      radicals in the pathogenicity of the defect.

PMID- 9593935
TI  - Synaptic and glial localization of the integrin alphavbeta8 in mouse and rat
      brain.
AB  - Integrins are a large family of cell adhesion receptors mediating cell
      extracellular matrix (ECM) interactions and are widely distributed in tissues.
      The beta8 integrin subunit mRNA has been shown to be expressed at higher levels
      in the central nervous system (CNS) than in other organs [M. Moyle, M.A. Napier,
      J.W. McLean, Cloning and expression of a divergent integrin subunit beta8, J.
      Biol. Chem. 266 (29) (1991) 19650-19658] but its cellular and subcellular
      localization in the CNS are unknown. In this report, we demonstrate that beta8
      pairs exclusively with the alphav subunit in the CNS to form the alphavbeta8
      heterodimer. Immunohistochemical analysis of the distribution of beta8 in adult
      mouse and rat brains revealed that the protein is expressed in several regions of
      the hippocampal formation and in the molecular layer and glomeruli of the
      granular cell layer of the cerebellum. Punctate and diffuse immunolabeling was
      observed occasionally surrounding neuronal pericarya and extensively throughout
      dendritic fields suggesting both pre- and post-synaptic localization and/or
      expression in non-neuronal cells. By immunoelectron microscopy, beta8
      immunoreactivity was detected in dendritic spines where it was often localized at
      post-synaptic densities, occasionally in axon terminals and in glial processes.
      Association of beta8 with synaptic membranes was further supported by its
      enrichment in synaptosomal preparations as detected by immunoblotting. These
      results demonstrate that alphavbeta8 is present in mature synapses and therefore
      may play a role in synaptic function.

PMID- 9593936
TI  - The effect of anabolic-androgenic steroids on aromatase activity and androgen
      receptor binding in the rat preoptic area.
AB  - The level of aromatase in the preoptic area of rats is transcriptionally
      regulated through a specific androgen-receptor mediated mechanism and can be used
      as a measure of central androgenic effect. Therefore, several commonly abused
      anabolic-androgenic steroids (AAS) were tested for their ability to induce
      aromatase activity in the preoptic area of castrated rats. In addition, we
      determined the relative binding affinities of these compounds for the androgen
      receptor, as well as their ability to bind androgen receptor in vivo following
      subcutaneous injections. All of the AAS compounds tested significantly stimulated
      POA aromatase activity above castrate levels. The compounds that produced the
      greatest stimulation of aromatase activity were those that bound most avidly to
      the androgen receptor in vitro (i.e., testosterone, dihydrotestosterone and
      nandrolone). In contrast, the 17alpha-alkylated compounds that were tested
      (stanozolol, danazol, methandrostenolone) modestly stimulated aromatase and were
      weak competitors for the androgen receptor. The subcutaneous injection of AAS
      compounds increased the concentrations of occupied nuclear androgen receptors in
      the brain, but the magnitude of effect was not related to their potency for
      inducing aromatase or their relative binding affinity for the androgen receptor
      suggesting that androgen receptor occupancy in POA is not correlated with the
      action of androgen on aromatase. The present results help explain the behavioral
      effects of AAS compounds in rats.

PMID- 9593937
TI  - The early component of the premovement readiness potential and its behavioral
      determinants.
AB  - Fifteen healthy subjects were asked to randomly select a tick of a mechanical
      clock which was operating throughout the experiment and to flex their wrist at
      the chosen tick. The individual averages of EEG recordings collected during the
      period of the putative decision to begin the task exhibited steep slopes of
      negativity followed by plateaus. These slopes preceded the selection of the
      signal sound at varying intervals, the longest interval was 3 s. The grand
      average of individual averages depicted a waveform whose shape was identical to
      the early component of the classical readiness potential. Another interesting
      finding came from experiments with mental counting of clock sounds, which
      demonstrated that the generation of the first mentally-counted number is preceded
      by a distinct negative potential shift.

PMID- 9593938
TI  - Developmental changes in subcellular AMPA/GluR receptor populations in rat
      forebrain.
AB  - Forebrains from rats of postnatal days (PND) 2, 7, 14, 21, and 30-40 were
      subjected to subcellular fractionation and samples from crude mitochondrial (P2,
      which contain synaptic plasma membranes) and microsomal (P3) fractions were used
      for SDS-PAGE and Western blotting with antibodies against GluR1, and GluR2/3
      subunits of AMPA/GluR receptors. GluR immunoreactivity in P2 fractions increased
      gradually from PND 2 to PND 30. In contrast, GluR immunoreactivity in P3
      fractions increased sharply at early postnatal ages, and was higher than in
      adults as early as at PND 7. Data were compared to postnatal changes in 3H-AMPA
      binding reported in various studies. Significant correlations were observed
      between changes in GluR immunoreactivity in P3 fractions and changes in high
      affinity binding on one hand and between changes in GluR immunoreactivity in P2
      fractions, and changes in low affinity binding. These data further establish that
      glutamate receptors present in different subcellular compartments represent
      different maturational states of the receptors, and suggest that changes in GluR
      populations could participate in mechanisms of synaptic plasticity.

PMID- 9593939
TI  - Stimulation of NTS activates NMDA and non-NMDA receptors in rat cardiac vagal
      neurons in the nucleus ambiguus.
AB  - While it is widely accepted that tonic and reflex changes in cardiac vagal
      activity play significant roles in cardiovascular function, little is known about
      the synaptic pathways in the brainstem responsible for the control of cardiac
      vagal neurons in the nucleus ambiguus (NA). In this study, we identified the
      principal post-synaptic receptors activated in cardiac vagal neurons upon
      stimulation of the nucleus tractus solitarius (NTS). Cardiac vagal neurons were
      identified by the presence of a retrograde fluorescent tracer and were visualized
      in rat brainstem slices. Perforated patch clamp techniques were used to record
      post-synaptic currents. NTS stimulation activated glutamatergic currents in
      cardiac vagal neurons with a typical delay of 8-18 ms. Post-synaptic responses
      were separated into NMDA and non-NMDA components using D-2-amino-5
      phophonovalerate (AP5) and 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX),
      respectively. In conclusion, this study characterizes a monosynaptic
      glutamatergic pathway from NTS that activates NMDA and kainate/AMPA post-synaptic
      receptors in cardiac vagal neurons.

PMID- 9593940
TI  - Heat shock protein 72 restores cyclic AMP accumulation after heat shock in N18TG2
      cells.
AB  - Although there are several reports on the alteration of intracellular signal
      transduction during heat shock in somatic cells, the long term effects of heat
      shock on neuronal cells remain unknown. In this report, we investigated cyclic
      AMP (cAMP) accumulation and the expression of heat shock proteins following heat
      shock in mouse neuroblastoma N18TG2 cells. Basal cAMP accumulation, or that
      stimulated by serotonin (10 microM), cholera toxin (1 microg/ml), and forskolin
      (1 microM) was suppressed at 0, 3, and 6 h following heat shock (45 degrees C for
      30 min). The cAMP levels were restored at 15 and 24 h after heat shock,
      corresponding with the expression of stress-induced heat shock protein 72
      (HSP72). Quercetin, an inhibitor of HSP expression, decreased the expression of
      HSP72 and inhibited the recovery of cAMP levels 24 h after heat shock. Quercetin
      also decreased the basal expression of the constitutive heat shock cognate
      protein 70 (HSC70) and suppressed cAMP accumulation in non-heat shocked cells.
      These results suggest that stress-induced HSP72 restores cAMP accumulation to
      control levels following heat shock and that constitutive HSC70 is related to
      cAMP levels in non-stress conditions.

PMID- 9593941
TI  - Differential magnetic resonance signal change in human sensorimotor cortex to
      finger movements of different rate of the dominant and subdominant hand.
AB  - Functional magnetic resonance tomography (fMRI) analysis of unimanual and
      bimanual sequential movements in righthanders showed the following effects.
      First, a rate-dependent activation of the somato-motor cortex was confirmed, with
      faster movement rates producing higher activation both in terms of signal
      intensity and number of activated voxels. Second, the right hemisphere showed
      more activation than the left hemisphere during unimanual tasks. Third, during
      bimanual movements, the left hemisphere showed greater activation than the right
      hemisphere. Finally, while the left hemisphere showed a marked change in
      activation patterns from unimanual to bimanual task, the right hemisphere
      activation patterns were not sensitive to task changes. The hemispheric
      asymmetries suggest substantial left hemisphere involvement in the coordination
      of bimanual tasks.

PMID- 9593942
TI  - Labeling of calcitonin gene-related peptide and substance P increases in
      subnucleus caudalis of rabbit during maxillary sinusitis.
AB  - Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P
      like immunoreactivity (SP-LI) were evaluated in subnucleus caudalis following
      induction of sinusitis. Three days after induction, intensity of labeling for
      CGRP-LI and SP-LI increased in ipsilateral subnucleus caudalis. Labeling for CGRP
      LI and SP-LI appeared normal at later time points (20 and 28 days). Early changes
      in these neuropeptides may contribute to the inflammatory process and painful
      symptoms accompanying sinusitis.

PMID- 9593943
TI  - Biallelic expression of all four IGF-II promoters and its association with
      increased methylation of H19 gene in human brain.
AB  - The human IGF-II gene is maternally imprinted in all tissues except adult liver
      and the choroid plexus/leptomeninges of the central nervous system where IGF-II
      is biallelically expressed. In human liver, it has recently been reported that
      this biallelic expression only involves the promoter P1 while the promoters P2-P4
      direct IGF-II transcription monoallelically. To explore whether or not biallelic
      expression of the IGF-II promoters in human CNS displays the same pattern as in
      liver, we examined the allelic expression status of the four IGF-II promoters in
      human brain. We found that all four IGF-II promoters in human fetal and adult
      brain were expressed from both parental alleles. Furthermore, the levels of
      methylation of the 3' region of H19 gene in fetal brain were higher than those in
      other tissues with monoallelic expression of IGF-II. Since similar findings have
      been reported in Wilms' tumor, these data suggest a similar mechanism may be
      responsible for loss of imprinting of IGF-II in normal brain and Wilms' tumor.

PMID- 9593945
TI  - Magnetic fields elicited by a tone onset time continuum in humans.
AB  - Event-related Fields (ERFs) were recorded in eleven normal volunteers in response
      to four two-tone stimuli selected from a tone onset time (TOT) continuum. The
      latter has been used extensively in the past as an analog of voice onset-time, an
      important cue for making voicing distinctions (e.g., ?pa? versus ?ba?). TOT
      values ranged from 0 to 60 ms in 20-ms steps. Three components of the ERF (P50m,
      N1m, and P2m) in the hemisphere contralateral to the stimulated ear were
      analyzed. The most significant finding was an abrupt reduction in the peak field
      amplitude of N1m (bilaterally) as TOT values increased from +20 to +40 ms. No
      systematic differences were noted between the 0 and +20 ms stimuli or between the
      +40 and +60 ms tokens. On the other hand, peak component latencies rose steadily
      with increasing TOT values. The discontinuity in the change of peak RMS as a
      function of TOT is in close agreement with behavioral evidence of categorical
      perception of similar non-speech as well as speech stimuli.

PMID- 9593944
TI  - Induction of cytokine-induced neutrophil chemoattractant in response to various
      stresses in rat C6 glioma cells.
AB  - The effect of stress on the production of cytokine-induced neutrophil
      chemoattractant (CINC) was examined in rat C6 glioma cells. We studied the
      production of CINC, an interleukin-8 (IL-8) family protein, with bacterial
      endotoxin, H2O2, and tumor necrosis factor-alpha (TNF-alpha). Each stress induced
      CINC mRNA in a concentration-dependent manner. Since stress activates the protein
      kinases regulating nuclear transcription factors, we examined the effects of
      protein kinase inhibitors and the over-expression of dominant-negative Ras on
      CINC mRNA expression. Neither over-expression of dominant-negative Ras nor
      pretreatment with PD98059 (MEK-1 inhibitor), SB203580 (p38MAPK inhibitor), or
      GF109203X (protein kinase C (PKC) inhibitor) altered stress-induced CINC mRNA
      expression. This suggests that the Ras-MAPK, p38MAPK, and PKC pathways are not
      involved in CINC mRNA expression in glial cells. On the other hand, pretreatment
      with herbimycin A, a potent tyrosine kinase inhibitor, or Ro31-8220, a non
      selective serine/threonine kinase inhibitor, suppressed stress-induced CINC mRNA
      expression. This indicates that stress-induced CINC mRNA expression is mediated
      by herbimycin A-, or Ro31-8220-sensitive kinases in glial cells. Since stress
      activates NF-kappaB and NF-IL6, we examined that the effect of herbimycin A,
      which suppresses CINC mRNA expression, on NF-kappaB and NF-IL6 activation.
      Herbimycin A suppressed NF-kappaB but not NF-IL6. These results suggest that in
      rat glial cells, the factors that induce CINC mRNA expression are mediated by
      herbimycin A-sensitive NF-kappaB activation, but not through the PKC, Ras-MAPK or
      p38 MAPK pathways.

PMID- 9593946
TI  - Comparison of the effects of M1 and M2 muscarinic receptor activation in the
      absence of GABAergic inhibition in immature rat hippocampal CA3 area.
AB  - We have reported previously that addition of carbachol (CCh, 25 microM) in the
      presence of the GABAA antagonist bicuculline (BMI, 10 microM), depresses evoked
      synaptic responses and significantly increases the frequency of spontaneous
      synchronous discharges in immature (postnatal days 10-20, P10-P20) hippocampus in
      vitro. The present experiments were designed in order to compare the activity of
      CCh with that of the selective muscarinic agonists McN-A-343 (M1 agonist) and
      oxotremorine-M (M2 agonist), in inducing the above-mentioned effects. Cholinergic
      agonists were tested in concentrations ranging from 2.5 nM to 5 microM and
      synaptic field potentials (evoked, spontaneous) were recorded from the CA3
      pyramidal layer of hippocampal slices in the presence of BMI (10 microM).
      Depression of the evoked responses was measured as decrease (i) in their
      duration, (ii) in the number of population spikes/response, and (iii) in the
      amplitude of the first population spike of each sequence. Sigmoid dose-response
      curves were plotted, and the IC50s were calculated. For all three indexes, the
      profile of effectiveness was Oxotremorine-M>carbachol=McN-A-343. CCh and
      oxotremorine-M induced or increased the frequency of spontaneous synchronous
      discharges in the presence of BMI in a concentration-dependent manner. At the
      range of concentrations tested, McN-A-343 did not mimic this effect. In
      conclusion, our results suggest that M2 muscarinic receptors play a major role in
      both the depression of synaptic responses and the increase in the frequency of
      spontaneous synchronous discharges observed in the absence of GABAergic
      inhibition.

PMID- 9593947
TI  - Complex I inhibitors as insecticides and acaricides.
AB  - Structurally diverse synthetic insecticides and acaricides had been shown to
      inhibit the proton-translocating NADH:ubiquinone oxidoreductase (complex I)
      activity. In addition, secondary metabolites from microbial and plant sources
      known to act on complex I exhibited biological activity against agricultural and
      environmental insect pests. Mechanistic studies indicated that these compounds
      interfered with ubiquinone reduction most likely at the same site(s) as the
      classical complex I inhibitors rotenone and piericidin A. Two approaches to
      characterize the mechanism of insecticidal/acaricidal complex I inhibitors were
      followed: enzyme kinetic studies and binding studies with radiolabeled
      inhibitors. Enzyme kinetic experiments were sometimes controversially interpreted
      regarding a competitive or non-competitive inhibitor mechanism with respect to
      the electron acceptor. In general, radioligand binding data with submitochondrial
      membranes were in line with the enzymological results but due to methodological
      drawbacks, saturation kinetic analyses were impossible. The main problems
      underlying many studies of inhibitor interaction with complex I were (i) the use
      of membrane-bound enzyme preparations and (ii) the physicochemical properties of
      the amphiphilic inhibitors with their strong tendency to accumulate in the
      membrane phase. A more recent approach to characterize inhbibitor interaction
      sites in complex I was the isolation of piericidin-resistant mutants of
      photosynthetic bacteria which produce a simpler homologue of mitochondrial NADH:Q
      oxidoreductase.

PMID- 9593948
TI  - Modulatory action of PACAP27 on NMDA receptor channel activity in cultured chick
      cortical neurons.
AB  - The modulatory effect of PACAP27 on NMDA receptor channel activity in cultured
      chick cortical neurons was investigated using the outside-out recording mode of
      the patch clamp technique. Channel opening frequency elicited by 20 microM NMDA,
      or 20 microM NMDA plus 1 microM glycine, was potentiated in the presence of 100
      nM PACAP27 and inhibited with 1000 nM PACAP27. These effects were reversible on
      washout and reduced when glycine concentration was increased to 10 microM, but
      were not affected by the PACAP antagonist PACAP6-27 (1 microM) or the GTP
      inhibitor GDP-beta-S (100 microM). It is suggested that PACAP27 may exert its
      modulatory action on NMDA receptor channel activity through the glycine site(s).

PMID- 9593949
TI  - Effects of the NMDA antagonist CP-98,113 on regional cerebral edema and
      cardiovascular, cognitive, and neurobehavioral function following experimental
      brain injury in the rat.
AB  - The present study examined the effects of CP-98,113, an N-methyl-d-aspartate
      (NMDA) receptor blocker, on cardiovascular variables, neurobehavioral motor
      function, spatial memory deficits, and cerebral edema formation following lateral
      (parasagittal) fluid-percussion (FP) brain injury in the rat. In Study 1, we
      compared the cardiovascular effects of i.p. administration of CP-98, 113 at 15
      min postinjury at doses of 1 mg/kg, 2 mg/kg, 5 mg/kg, or 20 mg/kg (n=8/dose).
      Animals receiving 1 mg/kg to 5 mg/kg CP-98,113 showed slight but nonsignificant
      decreases in blood pressure, while those receiving the highest dose (20 mg/kg)
      showed significant hypotension. Based upon those observations, the 5 mg/kg dose
      was chosen as the optimal dose for subsequent behavioral studies. In Study 2, 15
      min following lateral FP brain injury of moderate severity (2.5 atm), animals
      randomly received either CP-98,113 (5 mg/kg, i.p., n=23) followed by a 24-h
      subcutaneous infusion (1.5 mg kg-1 h-1) by means of a miniature osmotic pump, or
      identical volume of vehicle (n=24), and were evaluated for neurologic motor
      function (n=11/drug vs. 11/vehicle), memory function, and cerebral edema
      (n=12/drug vs. 13/vehicle). CP-98,113 (5 mg/kg) significantly attenuated
      neurologic motor dysfunction at 24 h (p<0.01) and 2 weeks (p<0.05) postinjury,
      reduced posttraumatic impairment in spatial memory observed at 48 h postinjury
      (p<0.001), and significantly reduced focal brain edema in the cortex adjacent to
      the site of maximal injury at 48 h postinjury (injury penumbra) (p<0.001). These
      results suggest that blockade of the NMDA receptor may attenuate the deleterious
      sequelae of traumatic brain injury.

PMID- 9593950
TI  - Sp1 as a target site for metal-induced perturbations of transcriptional
      regulation of developmental brain gene expression.
AB  - Differential gene expression is partially regulated by zinc finger proteins (ZFP)
      such as Sp1, which may be potential targets for perturbations by environmental
      metals. In this paper, we discuss the selective effects of lead (Pb) and other
      heavy metals on the in vitro and in vivo DNA-binding of Sp1, and the
      developmental expression of its target genes. We have found that the presence of
      Pb, Zn and Cd in a DNA-binding assay differentially modulated the binding of Sp1
      to its specific DNA sequence, while Ca, Mg and Ba, did not. In PC12 cells,
      cultured in the presence of low concentrations of Pb, a premature enhancement of
      Sp1 DNA-binding was observed. Similarly, Sp1 DNA-binding in the cerebellum of Pb
      exposed animals was shifted to the first week after birth, while the
      developmental profile of a non-ZFP, NFkB, was not. Furthermore, selective
      premature peaks of myelin basic protein and proteolipid protein mRNA expression
      were observed to occur in a manner relative to the changes in Sp1 DNA-binding.
      Since these genes are high targets for Sp1, these data suggest that exposure to
      heavy metals may alter developmental gene expression and brain development
      through selective modulation of the transcriptional activity of Sp1.

PMID- 9593951
TI  - Thoracic spinal neuron responses to repeated myocardial ischemia and epicardial
      bradykinin.
AB  - Bradykinin has been strongly implicated as a mediator of cardiac nociception.
      During coronary artery occlusion, the content of bradykinin in coronary sinus
      blood increases. In non-cardiac tissues nociception to bradykinin exhibits
      tachyphylaxis, however, this phenomenon has not been rigorously studied in the
      heart. This raises the question that repeated coronary occlusions may also result
      in tachyphylaxis, thereby reducing cardiac sensation on subsequent ischemic
      stimulation. We therefore examined the hypothesis that repetitive episodes of
      myocardial ischemia and of epicardial application of bradykinin demonstrate
      tachyphylaxis. Mongrel cats were anesthetized with alpha-chloralose and heart
      rate, arterial pressure, and thoracic spinal neuron firing rate were recorded
      during 60 s of anterior descending coronary occlusion or local epicardial
      application of bradykinin (10 microM). Neurons were identified by cutaneous
      receptive fields in the left shoulder area. Sixty-one of 93 neurons tested
      responded with an increase in firing rate to coronary artery occlusion only
      (n=24), bradykinin only (n=19) or to both (n=18). On repetitive coronary
      occlusion, 14 of 25 neurons demonstrated tachyphylaxis compared to 12 of 15
      tested with bradykinin (p<0.05). Similar responses were observed in thoracic
      spinal neurons that projected to the brain. In neurons demonstrating
      tachyphylaxis, dorsal cervical cold block partially restored the neuronal
      activation to coronary occlusion but not to bradykinin. We conclude, based on
      neuronal responses to repetitive stimuli, that afferent spinal responses to
      coronary occlusion and bradykinin are different. These data suggest that
      bradykinin is not the sole mediator of myocardial ischemic pain. The
      tachyphylaxis to repeated coronary artery occlusions may contribute to the
      clinical phenomenon of silent myocardial ischemia.

PMID- 9593952
TI  - Corticosterone attenuates zinc-induced neurotoxicity in primary hippocampal
      cultures.
AB  - Primary hippocampal cultures derived from newborn rats were exposed to zinc
      chloride at 50, 75, 100, 150 and 200 microM concentrations. Neuronal injury was
      assessed morphologically and by the lactate dehydrogenase (LDH) efflux assay.
      Zinc exposure increased LDH efflux in a concentration-dependent manner. Exposure
      to 100 microM zinc for 24 h resulted in beading of neurites and swelling of
      neuronal soma. When cultures were co-exposed to zinc at 100 microM and
      corticosterone in the range of 10-5 to 10-7 M, degeneration of neurons caused by
      zinc was attenuated. Our study suggests that corticosterone can protect neurons
      from zinc-induced neurotoxicity at low doses.

PMID- 9593953
TI  - Shifts of visual spatial attention modulate a steady-state visual evoked
      potential.
AB  - Although the effects of static allocations of visual spatial attention have been
      investigated using event-related potentials, most studies of shifts in visual
      spatial attention have been limited to behavioural measures. This study applied
      electroencephalographic measures to shifts in visual spatial attention in an
      effort to elucidate the time courses of such shifts. Using a custom-developed
      steady-state evoked potential analysis system, we analysed amplitude changes in
      EEG responses to rapid, periodic visual stimulation during a behavioural task
      that required rapid, repetitive shifts in visual spatial attention. Both stimulus
      evoked oscillations (that is, those signals whose phases matched the phase of the
      steady-state stimulus) and ongoing, background (non-phase-locked) oscillations
      were measured. This analysis revealed a transient increase in phase-locked
      amplitude, in the interval 0-300-ms post-stimulus, contralateral to the visual
      hemifield in which an attended target appeared. The magnitude of this increase
      varied with the length of the interval since the previous shift. In addition, by
      about 600-ms post-stimulus, phase-locked amplitude increased in the hemisphere
      contralateral to the newly-attended visual hemifield and decreased in the
      ipsilateral hemisphere. In the case of long inter-target intervals, phase-locked
      amplitude increased in the right hemisphere regardless of the laterality of the
      target. Non-phase-locked amplitude exhibited a complementary pattern of
      modulation: it decreased contralaterally to the newly-attended visual hemifield
      and increased ipsilaterally. These components may be electrophysiological
      concomitants of both transient and long-lasting alterations in neural function
      that implement shifts in visual spatial attention. In particular, we suggest that
      they may reflect orienting to a target stimulus, and reorienting to a cued
      location.

PMID- 9593954
TI  - The effects of aging on mu and delta opioid receptors in the spinal cord of
      Fischer-344 rats.
AB  - Previous research has demonstrated that the antinociceptive efficacy of opioids
      decreases with advancing age. This study utilized radioligand binding techniques
      to determine if this decline is due to a change in the receptor density (Bmax)
      and/or affinity (measured as Kd) of the mu (mu) and/or delta (delta) opioid
      receptors in the spinal cord with advancing age. Saturation binding analysis with
      [3H][d-Ala2,N-methyl-Phe4,Gly5-ol]enkephalin (DAMGO: a mu-opioid selective
      agonist) and [3H]naltrindole (a delta-opioid selective antagonist) revealed no
      age-related changes in Bmax for either the mu or delta-opioid receptors. The Kd
      value for naltrindole was likewise unaffected by age. The Kd value for DAMGO
      however, was significantly higher in the aged group as compared with the young
      and mature groups, indicating a decreased affinity of spinal mu-opioid receptors
      for DAMGO.

PMID- 9593955
TI  - NADPH-d positive neurons in the developing somatosensory cortex of the rat:
      effects of early and late environmental enrichment.
AB  - The effects of environmental enrichment upon the topographic arrangement of NADPH
      diaphorase-positive neurons (NADPH-d+ neurons) was studied in the somatosensory
      cortex of 56 Sprague-Dawley albino rats during early stages of development (18th,
      24th, 30th and 60th postnatal days). This diaphorase is easily demonstrable,
      providing a convenient marker for quantitative studies. Environmental enrichment
      diminished the number of NADPH-d+ neurons and exerted its maximal influence
      during lactation, a time of exceptional cortical susceptibility. This implies
      that the magnitude of such effects on the density of NADPH-d+ neurons is age
      dependent. Furthermore, it was found that the experience-dependent cortical
      changes persisted after a subsequent period without environmental stimulation.
      The effects of early environmental enrichment did not occur uniformly throughout
      the cerebral hemispheres but, instead, such effects were maximal in the latero
      ventral sector of the cerebral cortex where a dramatic reduction in the number of
      NADPH-d+ neurons was observed. Particularly striking was the existence of a
      latero-medial sequence of NADPH-d+ neurons in the infragranular layer and a
      reversed distribution of labeled cells, in the supragranular layer. Both
      ontogenetic sequences of NADPH-d+ neurons remained unchanged during postnatal
      development in controls and enriched subjects (18th-60th postnatal days).

PMID- 9593956
TI  - Pentylenetetrazole (PTZ)-induced c-fos expression in the hippocampus of kindled
      rats is suppressed by concomitant treatment with naloxone.
AB  - Rats were kindled by repeated injections of pentylenetetrazole (PTZ; 37.5 mg/kg;
      i.p.) in the presence or absence of the opioid receptor antagonist naloxone.
      Naloxone (10 mg/kg; i.p.) applied 30 min before each PTZ application had no major
      effect on the seizure development, although a slight decrease in the seizure
      expression of fully kindled animals could be observed. In the kindled animals, a
      pronounced but transient increase in c-fos mRNA level was observed in several
      brain areas after the injection of PTZ. The magnitude of c-fos induction was
      related to the seizure stage reached. Detectable c-fos mRNA levels in the cortex
      were observed in rats showing stage four seizures, whereas the expression of c
      fos in the hippocampus required stage five kindled seizures. The induction of c
      fos expression in the hippocampus of stage five kindled rats but not in other
      brain areas was prevented by treatment of naloxone prior to each PTZ application.
      In contrast, a single injection of naloxone to kindled rats was not sufficient to
      prevent c-fos mRNA expression in the hippocampus. In addition, a single PTZ
      application (at the higher dose of 45 mg/kg) to rats that were not kindled also
      caused c-fos expression in several brain regions, but this was not influenced by
      naloxone. Assuming that c-fos expression reflects neuronal activity our findings
      suggest a functional role of endogenous opioid peptides in the development of
      kindling-induced neuronal excitation in the hippocampus. In addition, the
      excitation of the hippocampus does not appear to be involved in the seizure
      activity but may be responsible for the impairment of learning in PTZ-kindled
      rats which can be prevented by pretreatment with naloxone [A. Becker, G.
      Grecksch, M. Brosz, Naloxone ameliorates the learning deficit induced by
      pentylenetetrazole kindling in rats, Eur. J. Neurosci. 6 (1994) 1512-1515].

PMID- 9593957
TI  - Hypothermia during or after severe perinatal asphyxia prevents increase in cyclic
      GMP-related nitric oxide levels in the newborn rat striatum.
AB  - The striatum is rich in nitric oxide synthase (NOS). It is present in a dense
      fiber network and in a few medium-sized non-spiny interneurons. Previous work
      showed chronic overexpression of NOS in the rat striatum after a severe perinatal
      asphyctic (SPA) insult. This was prevented by hypothermia. We investigated
      whether the overexpression of NOS was accompanied by increased NOS activity. As
      nitric oxide (NO) is a potent activator of the soluble isoform of guanylyl
      cyclase, we measured striatal 3',5'-cyclic monophosphate (cyclic GMP) synthesis
      in 10-day-old (P10) rat pups that were subjected to SPA during normothermia or
      hypothermia during or after the insult. Cyclic GMP levels in striatal tissue from
      control pups were approximately 25.8 pmol/mg protein and in the SPA group
      approximately 38.1 pmol/mg protein (p<0.01). Hypothermia, during as well as after
      insult, prevented this increase of cyclic GMP. Nomega-nitro-L-arginine (L-NAME)
      (0.1 mM) decreased cyclic GMP levels in control, SPA and hypothermia treated pups
      to similar low levels (approximately 8% of level without L-NAME). Sodium
      nitroprusside (SNP) stimulated cyclic GMP showed no differences between the four
      groups. This indicates that high cyclic GMP levels in the striatum of rats
      subjected to SPA are caused by increased NOS activity. Hypothermia after an
      asphyctic insult could be a promising treatment.

PMID- 9593958
TI  - Gap junction disappearance in astrocytes and leptomeningeal cells as a
      consequence of protozoan infection.
AB  - Trypanosoma cruzi and Toxoplasma gondii are protozoan parasites capable of
      causing infections of the nervous system. In order to determine effects of
      infection by these organisms on intercellular communication in the brain, dye
      coupling and connexin abundance and distribution were examined in leptomeningeal
      cells and astrocytes infected with T. cruzi or T. gondii. For both cell types
      infected with either type of protozoan parasite, intercellular diffusion of
      intracellularly injected Lucifer Yellow was dramatically reduced.
      Immunocytochemistry with antibodies specific for connexin43 (in astrocytes) or
      both connexin43 and connexin26 (for leptomeningeal cells) demonstrated that
      punctate gap junctional staining was much reduced in infected cells, although
      uninfected neighbors could display normal connexin abundance and distribution.
      Western blot analyses revealed that connexin43 abundance in both cell types
      infected with either parasite was similar to that in uninfected cells.
      Phosphorylation state of connexin43 (inferred from electrophoretic mobility of
      connexin43 isoforms) was not significantly affected by the infection process.
      Immunocytochemistry of whole brains from animals acutely infected with either
      parasite also showed a marked reduction in connexin43 expression. We conclude
      that infection of both types of brain cells with either protozoan parasite
      results in a loss of intercellular communication and organized gap junction
      plaques without affecting expression levels or posttranslational processing of
      gap junction proteins. Presumably, these changes in gap junction distribution
      result from altered targeting of the junctional protein to the plasma membrane,
      and/or from changes in assembly of subunits into functional channels.

PMID- 9593959
TI  - Behavioral effects of peripheral interleukin-1 administration in adult CD-1 mice:
      specific inhibition of the offensive components of intermale agonistic behavior.
AB  - Peripheral administration of interleukin-1beta (IL-1beta) in rodents reduces
      exploratory behavior in a novel environment while decreasing social investigation
      of a juvenile conspecific. In this study we wanted to test the effects of
      peripherally administered IL-1beta on another aspect of the mouse social
      repertoire, namely intraspecific fighting towards an adult male intruder. In the
      first experiment, sickness behavior induced by IL-1beta (1 microg/mouse) in adult
      CD-1 mice was assessed by direct observation of behavioral changes following
      placement into a novel environment. Three hours after injection, subjects were
      individually introduced for 20 min in a cage with clean sawdust and a number of
      behavioral items recorded. Blood samples were collected at the end of the testing
      session. Body temperature was measured right before, 1 h and 3.5 h following
      injection. In IL-1beta treated mice, exploration (assessed by measuring duration
      and frequency of Wall Rearing and Rearing behaviors) was nearly totally
      suppressed, while duration and frequency of behaviors such as Grooming, Bar
      Holding, and Digging were also markedly reduced. Administration of IL-1beta
      significantly elevated CORT secretion above basal levels and, as previously
      reported for mice, induced hypothermia (about 2 degrees C). In the second
      experiment, we assessed mice receiving IL-1beta (0.25; 0.5 or 1 microg/mouse or
      saline solution) in a social context. Three hours after injection, subjects were
      placed into a neutral cage for 20 min with a non-injected adult male conspecific
      and aggressive behavior scored. Overall, IL-1beta administration affected the
      social repertoire of treated mice in a dose-dependent fashion. Specifically,
      agonistic components of aggressive behavior were nearly totally suppressed, while
      the defensive elements, such as Upright Defensive posture, Upright Submissive
      posture, Crouching, or Flee were not affected by IL-1beta. Overall these data
      support the notion that sickness behavior induced by IL-1beta administration
      represents an organized behavioral strategy and is not an aspecific response to
      an illness-type of condition.

PMID- 9593960
TI  - Functional magnetic resonance imaging of category-specific cortical activation:
      evidence for semantic maps.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine the pattern of
      cortical activity during a picture naming task. Subjects (n=12) had to covertly
      name either animals or furniture items. Functional scanning was performed using a
      conventional 1.5-Tesla whole-body MRI system. Images obtained during naming the
      two categories were compared using a non-parametric test. The study revealed
      evidence for domain-specific lexical regions in left middle, right middle and
      inferior frontal areas, as well as in superior and middle temporal areas. The
      results corroborate neuropsychological data and demonstrate directly and non
      invasively in human volunteers that semantic representations in frontal and
      temporal areas are, to some degree, localized and possibly implemented as
      multiple maps. A completely distributed storage of semantic information is
      rendered unlikely.

PMID- 9593961
TI  - Axonal elongation through acellular nerve segments of the cat tibial nerve:
      importance of the near-nerve environment.
AB  - Peripheral nerve regeneration is considered to be influenced by structural,
      cellular and humoral factors in the distal nerve stump. Axonal elongation was,
      however, not affected by the presence of a 20 mm acellular nerve segment (ANS)
      distal to a crush lesion in a cat tibial nerve which was shielded from the
      environment by a silicone cuff [K. Fugleholm, H. Schmalbruch, C. Krarup, Early
      peripheral nerve regeneration after crushing, sectioning, and freeze studied by
      implanted electrodes in the cat, J. Neurosci., 14 (1994) 2659-2673]. In the
      present study axons were challenged to regenerate through crush lesions combined
      with 30-, 40-, 50-, 60- and 70-mm ANSs. For 30- and 40-mm ANSs, the nerves were
      shielded by impermeable silicone cuffs containing electrodes for
      electrophysiological evaluation of axonal elongation. All nerves were examined
      histologically by light microscopy 9 weeks after the lesion. The elongation
      through the shielded 30-mm ANS was slower than through a shielded nerve segment
      with viable cells. In the isolated 40-mm ANS, incomplete Wallerian degeneration
      and lack of blood vessels were observed, and axonal elongation was severely
      impaired. Regeneration across 40-70 mm non-shielded ANSs was intact and there was
      no relation between the number of regenerated fibers and the length of the ANS.
      There was no reduction in the number of blood vessels in the non-isolated ANSs.
      The results suggest that regeneration through an isolated acellular nerve segment
      exceeding 30 mm depends on cellular and humoral support from the near-nerve
      environment. Thus, the near-nerve environment is crucial for regeneration through
      long ANSs, and the importance of humoral, cellular and vascular support is
      discussed.

PMID- 9593962
TI  - Melanocortin-4 receptor mRNA expression in the developing autonomic and central
      nervous systems.
AB  - MC4-R mRNA expression was investigated in fetal rats (E14-E20) using in situ
      hybridisation. The autonomic nervous system showed the highest levels of MC4-R
      mRNA expression. In the spinal cord, dense signal was seen over the future
      intermediolateral cell column and dorsal horn. In the brain, MC4-R was expressed
      by E14 in diencephalon neuroepithelia, telencephalon, lamina terminalis and
      spinal trigeminal nucleus and was expressed by E19 throughout many regions of the
      brain.

PMID- 9593963
TI  - Low blood-brain barrier permeability to azidothymidine (AZT), 3TC, and thymidine
      in the rat.
AB  - The blood-brain barrier (BBB) permeability to [3H]-azidodeoxythymidine (AZT),
      deoxythiacytidine (3TC), and thymidine was studied using both an intravenous
      injection/external organ (IV/EO) method and an internal carotid artery perfusion
      (ICAP) technique in parallel with [14C]-sucrose as a plasma volume marker. The
      brain volumes of distribution (VD) of the three compounds approximated that of
      sucrose with either method. Although the lipid solubility of AZT, as determined
      by the 1-octanol/buffer partition coefficient (P), was 16-fold higher than that
      of thymidine, the BBB permeability-surface area (PS) products were almost
      identical, consistent with preferential efflux of AZT from brain to blood.

PMID- 9593964
TI  - Changes in the local metabolism of dopamine in the anterior and neural lobes but
      not in the intermediate lobe of the pituitary gland during nursing.
AB  - Dopamine (DA), produced by tubero-infundibular dopaminergic (TIDA) neurons of the
      arcuate nucleus (ARN) is the established inhibitor of the secretion of prolactin
      (PRL). Changes in dopaminergic (DAergic) neuronal activity in the median eminence
      long portal vessels (ME-LPV) and/or the concentration of DA in the anterior lobe
      (AL) are inversely related to the secretion of PRL. However, conflicting reports
      concerning DAergic neuronal activity during the suckling-induced release of PRL
      persist. In addition to TIDA neurons, PeVN-hypophysial DAergic (PHDA) and tubero
      hypophysial DAergic (THDA) neurons which, respectively, innervate the
      intermediate lobe (IL) and the IL/neural lobe (NL) also have a significant role.
      We measured the concentrations of DA and its main metabolite, 3, 4
      dihydroxyphenylacetic acid (DOPAC), in the median eminence and the three
      pituitary lobes of lactating mothers. Concentrations of DA and DOPAC from tissues
      and the concentration of PRL in plasma were measured by HPLC-EC and RIA,
      respectively. There were no changes in the concentration of DA and DOPAC of the
      IL due to the suckling stimulus. In the NL, a decrease in the concentration of
      DOPAC was detected due to the suckling stimulus. In addition, there were no
      changes of DA or DOPAC in the outer zone of the AL (AL-OZ) due to suckling.
      However, a decrease in the concentrations of DA and DOPAC was detected in the
      inner zone of the AL (AL-IZ). These data suggest lactotrophs from the AL-IZ are
      responsible for the changes in the concentration of plasma PRL in response to the
      suckling stimulus. In addition TIDA and THDA neurons, but not PHDA neurons,
      regulate the control of the secretion of PRL in response to suckling.

PMID- 9593965
TI  - Age-dependent regulation of seizure activity by nitric oxide in the developing
      rat.
AB  - The role of nitric oxide (NO) on the age-dependent selective vulnerability to the
      consequences of epileptic seizures was studied in 10-day old (P10) and 21-day old
      (P21) rats. At P10, the NO synthase (NOS) inhibitor, NG-nitro-l-arginine (LNA),
      increased severity of seizures while l-arginine (l-Arg), the NOS substrate, had
      no effect. At P21, l-Arg improved the outcome of seizures while LNA had no
      effect. These results demonstrated the age-dependent role of NO in epilepsy.

PMID- 9593966
TI  - Neurons in the hypothalamic paraventricular nucleus that project to the rostral
      ventrolateral medulla are activated by haemorrhage.
AB  - The retrogradely-transported tracer, rhodamine-tagged microspheres, was injected
      into the pressor region of the rostral ventrolateral medulla (RVLM) to identify
      paraventricular neurons in the hypothalamus that project to the RVLM. The
      protein, Fos, was detected immunohistochemically and used to highlight neurons
      that were activated by a hypotensive haemorrhage. Compared to controls, Fos
      production was increased by approximately 3-fold in the paraventricular nucleus
      (P<0.009) and there was a significant increase in the number of retrogradely
      labelled cells that expressed Fos. These represented 5% of the retrogradely
      labelled cell population. The results suggest that a small subpopulation of PVN
      neurons projecting to the RVLM are activated by haemorrhage and may be involved
      in the reflex responses initiated by that stimulus.

PMID- 9593967
TI  - Widespread expression of ecto-apyrase (CD39) in the central nervous system.
AB  - We have shown that ecto-apyrase protein is expressed in primary neurons and
      astrocytes in cell culture (T.-F. Wang, P.A. Rosenberg, G. Guidotti, 1997. Mol.
      Brain Res. 1997, 47: 295-302). Here we present immunohistochemical studies
      showing that ecto-apyrase protein is widely distributed in rat brain, as it is
      present in neurons of the cerebral cortex, hippocampus and cerebellum as well as
      in glial cells and endothelial cells. Ecto-apyrase is enriched in brain
      postsynaptic density membrane fractions and is localized in proximity to
      synaptophysin, the marker of synaptic vesicles. These results together with the
      observation that P2 purinergic receptors are present throughout the brain suggest
      that ecto-apyrase is involved in regulating synaptic transmission mediated by
      extracellular ATP.

PMID- 9593968
TI  - GABA modulates color-opponent bipolar cells in carp retina.
AB  - In the present work, the effects of gamma-aminobutyric acid (GABA) were examined
      while recording intracellularly from color-opponent bipolar cells in the
      isolated, superfused carp retina. Bath-applied GABA differentially suppressed
      light responses of R/G cells, which depolarized and hyperpolarized, respectively,
      in response to red and green flashes, and G/R cells, which showed the opposite
      responses. In either R/G or G/R cells, the response driven by input from red
      cones was invariably suppressed to a greater extent. Such effects of GABA were
      completely blocked by picrotoxin, but only partially by bicuculline, suggesting
      that the GABAC receptor, in addition to the GABAA receptor, may also be involved.
      It is postulated that GABA modulates the color-opponent bipolar cells either
      through activating GABA receptors on these cells directly or those on cone
      terminals indirectly.

PMID- 9593969
TI  - Aging and the effects of MK-801 on anoxic damage in rat hippocampal slices.
AB  - We examined whether age-related differences in N-methyl-D-aspartate (NMDA)
      receptor-mediated neurotoxicity contribute to the increased vulnerability of the
      aged brain to anoxic damage. In both adult and aged hippocampal slices, NMDA
      receptor blockade with MK-801 did not affect the onset of anoxic depolarization.
      MK-801 improved the postanoxic recovery of synaptic transmission by the same
      percentage in both age groups. Thus, the faster onset of anoxic depolarization
      and diminished postanoxic recovery of synaptic transmission seen in aged
      hippocampal slices cannot be attributed to age-related differences in NMDA
      receptor-mediated neurotoxicity.

PMID- 9593970
TI  - Electrophysiological evidence of a perceptual precedence of global vs. local
      visual information.
AB  - Aim of the present study was to investigate the mechanisms of attentional
      selection of hierarchically organized visual patterns (compound letter stimuli),
      while subjects were engaged in target selection at either the global or local
      level. Event-related brain potentials (ERPs) were recorded using a high density
      electrode montage. Reaction times (RTs) to target stimuli were also recorded. RT
      data indicated the interference effect of global incongruent information with the
      local one. ERP data were consistent with behavioral data. In fact, the early
      sensory N115 component recorded at the primary visual areas exhibited smaller
      responses to locally attended elements when the global configuration was
      incongruent rather than congruent, suggesting an interference effect of the
      global with the local level. Conversely, no interference effect was found for
      globally attended configurations. These results strongly support the view of a
      perceptual advantage of globally conveyed information, very likely mediated by
      low spatial frequency channels. At later processing levels, N1 and P3 components
      were faster and larger when attention was paid to the global configuration. The
      difference between target and nontarget responses, indexing the attentional
      target selection, yielded a broad occipital-temporal negativity focused onto the
      left hemisphere in the attend-local, and over the right hemisphere in the attend
      global condition. The present findings indicate a hemispheric asymmetry in
      cerebral activation during local/global processing. In addition, they provide
      robust evidence of a sensory precedence of global information.

PMID- 9593971
TI  - 5-HT1B receptor binding in degenerative movement disorders.
AB  - Using [3H]sumatriptan as a radioligand, 5-hydroxytryptamine (5-HT)1B receptors
      were examined in posterior striatum and midbrain post-mortem tissue sections of
      12 patients who had died from representative degenerative movement disorders as
      compared to nine controls. In the control human basal ganglia, the highest
      densities of [3H]sumatriptan binding were observed in the globus pallidus and
      substantia nigra. No significant change in the density of [3H]sumatriptan binding
      sites was found in the striatum and substantia nigra of the six Parkinson's
      disease brains. In the two brains from patients with progressive supranuclear
      palsy an increase was found in the densities of [3H]sumatriptan binding sites,
      most marked in the substantia nigra. In contrast, [3H]sumatriptan labelling was
      almost absent in the striatonigral degeneration brain and was markedly reduced in
      the three Huntington's disease brains. This study indicates that the status of 5
      HT1B receptors is different in each degenerative movement disorder and suggests
      that human 5-HT1B receptors are located somatodendritically on GABAergic and
      peptidergic caudate-putamen neurons which project to the substantia nigra and
      globus pallidus, where these receptors are presynaptic.

PMID- 9593972
TI  - Local injection of alkylating and nonalkylating dopamine receptor antagonists
      into rat basal forebrain: autoradiographic assessment of D2-like and D3 sites.
AB  - N-chloroethyl derivatives of 7-hydroxy-1,2,3,4-tetrahydronaphthalene (7-OH-DPAT),
      1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), or fluphenazine were
      microinjected into rat nucleus accumbens (Acc), and receptor binding quantified
      autoradiographically after 24 h. EEDQ reduced [3H]nemonapride (D2-like receptors)
      binding in Acc (by 84%) and islands of Calleja (IC; 44%), without affecting
      [3H](+)-7-OH-DPAT (D3); N-chloroethyl-7-OH-DPATs blocked both radioligands in Acc
      and IC (30%-70%); fluphenazine had no effect.

PMID- 9593973
TI  - Development of laminar distributions of kainate receptors in the somatosensory
      cortex of mice.
AB  - Kainate receptors were present at birth in the murine somatosensory cortex as
      revealed by quantitative in vitro autoradiography. During the first five
      postnatal days [3H]kainate binding rapidly increased and the maximum density in
      layer IV was reached at P12. The adult laminar pattern of receptor binding
      distribution was established by the third postnatal week with the heaviest
      labeling of infragranular layers. The sharp increase of kainate receptor during
      the first postnatal week coincides with the critical period for cytoarchitectonic
      plasticity of the barrels and establishment of functional thalamo-cortical
      connections in the barrel field.

PMID- 9593974
TI  - Orphanin FQ/nociceptin analgesia in the rat.
AB  - The heptadecapeptide orphanin FQ or nociceptin (OFQ/N), the endogenous ligand for
      the orphan opioid receptor, has a complex pharmacology in mice, eliciting either
      an anti-opioid/hyperalgesic action or analgesia depending upon the dose and
      testing paradigm. Unlike mice, orphanin FQ/nociceptin fails to elicit
      hyperalgesia in the rat following intracerebroventricular injection. Both OFQ/N
      and a truncated version, OFQ/N(1-11), produce a robust analgesic response. OFQ/N
      analgesia is readily antagonized by the opioid antagonists naloxone or
      diprenorphine, despite their very poor affinity for the cloned orphan opioid
      receptor. Antisense studies revealed that probes targeting the second and third
      coding exon of the orphan clone significantly attenuate OFQ/N analgesia, while
      the exon 1 probe was inactive. These results indicate that OFQ/N elicits a
      naloxone-sensitive analgesia in rats similar to that previously reported in mice.

PMID- 9593975
TI  - Evidence that GABA augmentation of norepinephrine release is mediated by
      interneurons.
AB  - GABAA receptor activation augments stimulated release of 3H-norepinephrine (NE)
      in brain slices from female rats. This effect is not blocked by acetazolamide or
      MK-801, indicating that permeability of the GABAA chloride channel to bicarbonate
      ions and NMDA receptor activation do not mediate GABA-induced NE release.
      Furthermore, GABA augments 3H-NE release from slices, but not from isolated nerve
      terminals (synaptosomes), indicating that interneurons mediate GABA effects on 3H
      NE release.

PMID- 9593976
TI  - Lamotrigine may limit pathological excitation in the hippocampus by modulating a
      transient potassium outward current.
AB  - Actions of the new antiepileptic drug lamotrigine were characterised using whole
      cell patch clamp recordings from rat CA1 pyramidal cells in vitro. The results
      suggest that lamotrigine, besides its previously described effect on the fast
      sodium inward current and calcium currents, modulates the transient potassium
      outward current ID. This may be an effective mechanism to inhibit pathological
      excitation.

PMID- 9593977
TI  - Stimulation of alpha4beta2 nicotinic acetylcholine receptors inhibits beta
      amyloid toxicity.
AB  - We examined the effects of nicotinic receptor agonists against beta amyloid
      (Abeta) cytotoxicity to rat cortical neurons. Administration of nicotine
      protected against Abeta-induced neuronal death. This neuroprotection was blocked
      by dihydro-beta-erythroidine, an alpha4beta2 nicotinic receptor antagonist.
      Furthermore, incubation with cytisine, a selective alpha4beta2 nicotinic receptor
      agonist, inhibited Abeta cytotoxicity. These results suggest that alpha4beta2
      nicotinic receptor activation plays an important role in neuroprotection against
      Abeta cytotoxicity.

PMID- 9593978
TI  - Opposing effects of different steroid sulfates on GABAA receptor-mediated
      chloride uptake.
AB  - Steroids with the 3alpha-hydroxy-5alpha- or 5beta-reduced configurations of the A
      ring interact with the gamma-aminobutyric acid (GABA) type A receptor chloride
      channel complex and potentiate the stimulation of Cl- uptake by GABA agonists.
      Conversely, the sulfate esters of 3beta-hydroxy-5-ene neurosteroids pregnenolone
      and dehydroepiandrosterone behave as inhibitory modulators. In the present work,
      steroid sulfates were tested for their ability to modulate muscimol-induced
      chloride ion uptake into cortical synaptoneurosomes. 3alpha-Hydroxy-5alpha
      pregnan-20-one sulfate and several other 3alpha-hydroxy-steroid sulfates
      potentiated, whereas 3beta-hydroxy-steroid sulfates inhibited muscimol effect. It
      is concluded that GABA-agonistic or antagonistic properties of steroid sulfates
      depend on the alpha or beta orientation of the sulfate moiety linked to the A
      ring.

PMID- 9593979
TI  - Corticostriatal input zones from the supplementary motor area overlap those from
      the contra- rather than ipsilateral primary motor cortex.
AB  - To investigate the degree of convergence of corticostriatal inputs from the
      primary motor cortex (MI) and the supplementary motor area (SMA), we analyzed the
      extent to which corticostriatal inputs from forelimb representations of these
      motor-related areas spatially overlap in the macaque monkey. Of particular
      interest was that corticostriatal input zones from SMA overlapped those from MI
      of the contralateral hemisphere more extensively than from MI of the ipsilateral
      hemisphere.

PMID- 9593980
TI  - Neural network classifications and correlation analysis of EEG and MEG activity
      accompanying spontaneous reversals of the Necker cube.
AB  - It has recently been suggested that reentrant connections are essential in
      systems that process complex information [A. Damasio, H. Damasio, Cortical
      systems for the retrieval of concrete knowledge: the convergence zone framework,
      in: C. Koch, J.L. Davis (Eds.), Large Scale Neuronal Theories of the Brain, The
      MIT Press, Cambridge, 1995, pp. 61-74; G. Edelman, The Remembered Present, Basic
      Books, New York, 1989; M.I. Posner, M. Rothbart, Constructing neuronal theories
      of mind, in: C. Koch, J.L. Davis (Eds.), Large Scale Neuronal Theories of the
      Brain, The MIT Press, Cambridge, 1995, pp. 183-199; C. von der Malsburg, W.
      Schneider, A neuronal cocktail party processor, Biol. Cybem., 54 (1986) 29-40].
      Reentry is not feedback, but parallel signalling in the time domain between
      spatially distributed maps, similar to a process of correlation between
      distributed systems. Accordingly, it was expected that during spontaneous
      reversals of the Necker cube, complex patterns of correlations between
      distributed systems would be present in the cortex. The present study included
      EEG (n=4) and MEG recordings (n=5). Two experimental questions were posed: (1)
      Can distributed cortical patterns present during perceptual reversals be
      classified differently using a generalised regression neural network (GRNN)
      compared to processing of a two-dimensional figure? (2) Does correlated cortical
      activity increase significantly during perception of a Necker cube reversal? One
      second duration single trials of EEG and MEG data were analysed using the GRNN.
      Electrode/sensor pairings based on cortico-cortical connections were selected to
      assess correlated activity in each condition. The GRNN significantly classified
      single trials recorded during Necker cube reversals as different from single
      trials recorded during perception of a two-dimensional figure for both EEG and
      MEG. In addition, correlated cortical activity increased significantly in the
      Necker cube reversal condition for EEG and MEG compared to the perception of a
      non-reversing stimulus. Coherent MEG activity observed over occipital, parietal
      and temporal regions is believed to represent neural systems related to the
      perception of Necker cube reversals.

PMID- 9593982
TI  - Spatial-tuning properties of auditory neurons in the optic tectum of the pigeon.
AB  - We studied the auditory neurons in the optic tectum of the unanesthetized pigeon,
      using single-unit recordings and acoustic free-field stimulation. Most units
      showed spatial tuning, with best areas located in the contralateral hemifield.
      All units responded also to visual stimuli, the auditory best areas being in
      rough alignment with visual receptive fields.

PMID- 9593981
TI  - Stimulatory effects of 4-methylcatechol, dopamine and levodopa on the expression
      of metallothionein-III (GIF) mRNA in immortalized mouse brain glial cells (VR
      2g).
AB  - Metallothionein (MT)-III, originally discovered as a growth inhibitory factor
      (GIF), is a brain specific isomer of MTs and is markedly reduced in the brain of
      Alzheimer's disease patients (AD) and in several other neurodegenerative
      diseases. We analyzed the level and regulation of mRNA expression of MT-III in
      immortalized fetal mouse brain glial cells (VR-2g) by reverse transcriptase
      polymerase chain reaction (RT-PCR). The basal expression level of MT-III mRNA is
      very low in VR-2g cells. 4-Methylcatechol, dopamine (DA) and levodopa (l-3, 4
      dihydroxyphenylalanine), which stimulate the synthesis of nerve growth factor
      (NGF), further increased the expression of MT-III mRNA in VR-2g cells.

PMID- 9593983
TI  - Vasopressin location and relative quantification within the vampire bat (Desmodus
      rotundas) brain.
AB  - Vasopressin was localized in the supraoptic nucleus (SON), paraventricular
      nucleus, amygdala, habenula, and the posterior pituitary. Microdensitometry
      analysis revealed an inversely proportionate relationship between the relative
      vasopressin levels in the SON and the posterior pituitary when exposed to varying
      periods of dehydration. Short term dehydrated bats displayed increased
      vasopressin in the SON and decreased levels in the posterior pituitary.
      Chronically dehydrated bats displayed decreased vasopressin in the SON with
      increased levels in the posterior pituitary.

PMID- 9593984
TI  - mu-Opioid agonist-stimulated [35S]GTPgammaS binding in guinea pig hypothalamus:
      effects of estrogen.
AB  - mu-Opioid receptors play a critical role in the regulation of the female
      reproductive cycle, and estrogen modulates the coupling of mu-opioid receptors to
      a potassium channel in the basal hypothalamus (BH) of the female guinea pig.
      Therefore, we ascertained the distribution of mu-opioid receptors in the BH with
      autoradiography using the mu-opioid selective agonist [3H]DAMGO. In addition, we
      investigated the effects of estrogen on DAMGO- or the GABAB receptor agonist
      baclofen-stimulated [35S]GTPgammaS binding in the BH. Based on the high density
      of mu-opioid receptors, but the lack of effects of estrogen on [35S]GTPgammaS
      binding, we conclude that mu-opioid receptor interaction with its G-protein is
      not the target of estrogen's actions.

PMID- 9593985
TI  - Swim stress triggers the release of vasopressin within the suprachiasmatic
      nucleus of male rats.
AB  - The hypothalamic suprachiasmatic nucleus (SCN) is the predominant pacemaker of
      the mammalian brain that generates and controls circadian rhythms of various
      endocrine and behavioral processes. Different lines of evidence suggest that
      stress interferes with the maintenance of such rhythms. As a first approach to
      investigate whether the neuropeptide arginine vasopressin (AVP), which shows
      circadian rhythms of synthesis and release within the SCN, might contribute to
      this stress-induced alterations in circadian rhythms, we monitored acute effects
      of swim stress on the intra-SCN release of AVP in male rats by means of the
      microdialysis technique. A 10-min forced swimming session triggered a marked but
      relatively short-lasting increase in the intranuclear release of AVP (to approx.
      440%). This effect was restricted to the area containing predominantly somata and
      dendrites of vasopressinergic neurons, since no changes in AVP release could be
      measured in one of their major projection areas, the nucleus of the dorsomedial
      hypothalamus. Our data provide evidence that the amount of AVP released within
      the SCN can vary widely not only in accordance with AVP's intrinsically regulated
      circadian rhythm but also in response to a physiologically relevant stressor. In
      this way, the neuropeptide may contribute to the regulation of endocrine and
      behavioral rhythms particularly in challenging situations associated with
      resettings of the endogenous clock.

PMID- 9593986
TI  - PACAP stimulates dopamine neuronal activity in the medial basal hypothalamus and
      inhibits prolactin.
AB  - In sheep intracerebroventricular injection of PACAP (10 nmol) significantly
      (P<0.01) stimulated the levels of the dopamine metabolite DOPAC within the medial
      basal hypothalamus (as measured by in vivo microdialysis) and this effect was
      temporally correlated with a significant (P<0.05) suppression in peripheral
      prolactin concentrations. This result is in accord with the hypothesis that PACAP
      suppresses prolactin secretion from the anterior pituitary gland by stimulating
      dopamine release from tuberoinfundibular dopaminergic neurons.

PMID- 9593987
TI  - Translocation of phosducin in living neuroblastoma x glioma hybrid cells (NG 108
      15) monitored by red-shifted green fluorescent protein.
AB  - Activation of G protein-coupled receptors triggers translocation of certain
      proteins from cytoplasm to cell membrane located targets. One of these cytosolic
      proteins is phosducin (Phd) which has been described to compete with G protein
      coupled receptor kinases for Gbetagamma dimers attached to the cell membrane,
      thereby attenuating desensitization of activated receptors. These features of
      protein redistribution prompted us to examine whether stimulation of membrane
      associated E-prostaglandin receptors coupled to Gs causes Phd to migrate towards
      the plasma membrane. We made use of enhanced green fluorescence protein (EGFP), a
      reporter protein, to follow redistribution of Phd both by means of confocal
      microscopy and biochemical techniques in living neuronal NG 108-15 hybrid cells
      challenged with prostaglandin E1 (PGE1). The cells were transiently transfected
      to express Phd fused to the C-terminus of EGFP, or to express EGFP only.
      Overexpression of the proteins is implied by FACS analysis as well as by western
      blot technique, and the functional integrity of EGFP-tagged Phd was confirmed by
      its ability to elevate cAMP accumulation. Time-lapse imaging of single living
      cells by means of confocal microscopy revealed that exposure to prostaglandin
      causes EGFP/Phd, which is evenly spread throughout the cell, to relocate towards
      the membrane within few minutes. Fluorescence associated with the cell nucleus
      displayed little rearrangement. The principle finding that prostaglandin triggers
      translocation of Phd from cytosol to the cell periphery was verified with
      membranes prepared from EGFP/Phd expressing cells. We found maximal
      concentrations of membrane associated fluorescent material 5 to 7 min upon
      prostaglandin exposure. The present study reports for living NG 108-15 hybrid
      cells that PGE1 stimulation causes cytosolic Phd to translocate towards the
      membrane, where it is believed to bind to G protein subunits such as Gbetagamma
      and Galphas.

PMID- 9593988
TI  - Changes in the hippocampus induced by glucose in thiamin deficient rats detected
      by MRI.
AB  - Using T2-weighted Magnetic Resonance Imaging (MRI) in a pyrithiamin-treated,
      thiamin deficient (TD) rat model of Wernicke's encephalopathy (WE), we have
      observed hyperintensity in the thalamus, hypothalamus, collicular bodies and
      hippocampus which was enhanced 40 min after a glucose load. Hyperintensity was
      not evident in these structures in thiamin replete rats receiving glucose nor was
      it enhanced in TD rats administered 2-deoxyglucose. Residual hyperintensity was
      still evident in the hippocampus as long as 30 days after thiamin administration
      and was increased by repeat glucose challenge at that time. These data indicate
      that the hippocampus is as vulnerable as the thalamus to some persistent
      pathological change when glucose is metabolised in a state of thiamin deficiency.

PMID- 9593989
TI  - Simultaneous learning of motion discrimination in two directions.
AB  - We take issue with theories about the direction specificity in perceptual
      learning of motion discrimination. Trials of motion discrimination in two
      opposite directions were interleaved in uneven proportions (2:1). Human subjects
      improved faster in the direction with less frequent trials, indicating that
      learning transferred from the more frequent to the less frequent direction.

PMID- 9593990
TI  - Expression of c-fos, fos B, and egr-1 in the medial preoptic area and bed nucleus
      of the stria terminalis during maternal behavior in rats.
AB  - The spatial and temporal pattern of expression of the protein products of
      immediate early genes (IEGs) c-fos, fos B, and egr-1 were mapped in medial
      preoptic area (MPOA) and ventral bed nucleus of stria terminalis (VBST) during
      maternal behavior in rats. Immunocytochemical analysis indicated significant
      increases in the number of cells expressing c-Fos after 2 h of pup exposure,
      while Fos B levels showed a delayed response, reaching maximal levels after 6 h.

PMID- 9593991
TI  - Males and females use different distal cues in a virtual environment navigation
      task.
AB  - The study of navigational ability in humans is often limited by the restricted
      availability and inconvenience of using large novel environments. In the present
      study we use a computer-generated virtual environment to study sex differences in
      human spatial navigation. Adult male and female participants navigated through a
      virtual water maze where both landmarks and room geometry were available as
      distal cues. Manipulation of environmental characteristics revealed that females
      rely predominantly on landmark information, while males more readily use both
      landmark and geometric information. We discuss these results as a possible link
      between recent human research reporting hippocampal activation in spatial tasks
      and animal work showing sex differences in both spatial ability and hippocampal
      development.

PMID- 9593992
TI  - Indomethacin inhibits delayed DNA fragmentation of hippocampal CA1 pyramidal
      neurons after transient forebrain ischemia in gerbils.
AB  - Recent studies have shown a close association between reactive oxygen species and
      DNA fragmentation and that delayed neuronal death after transient forebrain
      ischemia manifests as DNA fragmentation-like apoptosis. We examined the effect of
      indomethacin on ischemic-induced delayed hippocampal neuronal death in gerbils
      using the TUNEL staining method, since indomethacin is neuroprotective in a
      variety of degenerative processes, such as Alzheimer's disease. Indomethacin (5
      mg/kg, i.p.), administered 5 min before the ischemic insult, significantly
      decreased the number of TUNEL-positive hippocampal CA1 pyramidal neurons and
      delayed the appearance of TUNEL-positive neurons. Our results indicate that
      indomethacin is effective in inhibiting DNA fragmentation after transient
      forebrain ischemia.

PMID- 9593993
TI  - Effect of lipopolysaccharide on the permeability and reactivity of the cerebral
      microcirculation: role of inducible nitric oxide synthase.
AB  - The goal of this study was to examine the effect of lipopoly saccharide on the
      permeability of the blood-brain barrier and reactivity of cerebral arterioles. We
      examined the pial microcirculation in rats using intravital fluorescence
      microscopy. Permeability of the blood-brain barrier (clearance of fluorescent
      labeled dextran; molecular weight 10,000 Da; FITC-dextran-10K) and diameter of
      pial arterioles were measured in the absence and presence of topical application
      of vehicle (saline) or lipopolysaccharide (200 ng/ml). During superfusion with
      vehicle, clearance of FITC-dextran-10K from pial vessels was minimal, and
      diameter of pial arterioles remained constant. Topical application of
      lipopolysaccharide (200 ng/ml) produced an increase in clearance of FITC-dextran
      10K and dilated pial arterioles. To determine whether lipopolysaccharide-induced
      changes in permeability of the blood-brain barrier and dilatation of cerebral
      arterioles was related to the synthesis/release of inducible nitric oxide, we
      examined the effects of aminoguanidine (0.5 mM). Aminoguanidine inhibited
      lipopolysaccharide-induced increases in permeability of the blood-brain barrier
      and dilatation of cerebral arterioles. The findings of the present study suggest
      that lipopolysaccharide increases permeability of the blood-brain barrier and
      diameter of pial arterioles via the activation of inducible nitric oxide
      synthase.

PMID- 9593994
TI  - C-type natriuretic peptide exerts effects opposing those of atrial natriuretic
      peptide on anxiety-related behaviour in rats.
AB  - As evidence exists that C-type natriuretic peptide (CNP) exerts effects opposing
      those of atrial natriuretic peptide (ANP), we studied the behavioural properties
      of CNP after central infusion in rats by their performance in the elevated plus
      maze. Doses of 0.5 microg and 5 microg i.c.v. had distinct anxiogenic properties.
      Our data suggest opposing effects of CNP and ANP on anxiety-related behaviour in
      rats, which appear to be mediated via different receptor occupation and brain
      regions by a corticotropin-releasing hormone (CRH)-dependent mechanism.

PMID- 9593997
TI  - [Editorial]

PMID- 9593996
TI  - [Tuberculosis among the Amerindian population of the upper Rio Negro region]
AB  - The presence of tuberculosis in the upper Rio Negro region (Brazil) dates to the
      early 20th century. A retrospective survey of medical records in two clinics (one
      from 1977 and the other from 1990) showed 699 cases, with an extremely high
      annual incidence rate of over two per thousand, predominantly pulmonary cases,
      and distribution of the disease among all age groups. Data on compliance with
      outpatient treatment are not reliable. In the present context of deteriorating
      environmental and socioeconomic conditions among Indians, tuberculosis incidence
      may increase. Control of this disease could be enhanced by improving living
      conditions and health services for indigenous peoples.

PMID- 9593995
TI  - Phase-relationship and mutual effects between circadian rhythms of ocular
      melatonin and dopamine in the pigeon.
AB  - In order to study the mechanisms of ocular circadian rhythms in the pigeon, we
      measured melatonin and dopamine simultaneously from the eye using in vivo
      microdialysis. In experiment 1, the phase relationship between circadian rhythms
      of ocular melatonin and dopamine under light-dark cycles (LD) and continuous dim
      light (LLdim) was examined. Under LD, melatonin was high during the dark and low
      during the light. On the other hand dopamine was high during the light and low
      during the dark. These rhythms with the anti-phase relationship were maintained
      after the birds were transferred from LD to LLdim. In experiment 2, effects of a
      single light pulse on melatonin and dopamine rhythms were examined. A light pulse
      at CT18 rapidly suppressed melatonin release to the daytime level, whereas it
      rapidly increased dopamine release to the daytime level. The light pulse also
      affected the phases of melatonin and dopamine rhythms, inducing phase advances of
      both rhythm without changing the anti-phase relationship before the light pulse.
      In experiment 3, effects of an intraocular injection of dopamine or melatonin on
      their circadian rhythms were examined. A dopamine injection during the subjective
      night suppressed melatonin release and induced a light-pulse type phase shift in
      both melatonin and dopamine rhythms. On the other hand, a melatonin injection
      during the subjective day suppressed dopamine release and induced a dark-pulse
      type phase shift. These results are compatible with either one or two oscillator
      models, but the interaction between melatonin and dopamine is, in either case
      considered as an important mechanism regulating ocular circadian rhythms of the
      pigeon.

PMID- 9593998
TI  - [Dilemmas in assisted reproduction]
AB  - Modern reproductive technologies, particularly in vitro fertilization (IVF) and
      gamete intrafallopian transfer (GIFT), have made possible the establishment of
      new families through the birth of hundreds of thousands of children worldwide.
      Meanwhile, these technologies have compelled men to face the possibility of
      intervening at the very origins of their own biological existence, hence creating
      doubts and questions beyond the domain of medical science. Society is now asking
      itself whether all that is scientifically and technically possible is necessarily
      beneficial to mankind. The answer to this question is not to be found in
      biological science alone, but instead requires multidisciplinary reflection
      including all forms of knowledge: philosophical, bioethical, and religious, all
      contributing to the unavoidable adventure that we are endowed with in the search
      for a better life.

PMID- 9593999
TI  - [The Program for Integrated Women's Health Care]
AB  - The Program for Integrated Women's Health Care (PAISM) was launched by the
      Brazilian Ministry of Health in 1983 as a new and different approach to women's
      health. Paradoxically, the PAISM also became the first case in which the
      Brazilian state explicitly proposed and implemented (albeit partially) a program
      regulating fertility. This raised suspicions as to disguised promotion of birth
      control. However, a brief analysis of the history of this program and its social
      significance suggests that the PAISM was a pioneering undertaking (even within
      the international scenario) in proposing integrated women's health care as
      opposed to isolated family planning measures. This helps explain why women's
      movements in Brazil immediately began to struggle to see it properly implemented.
      The program contained the definition of reproductive health adopted by the World
      Health Organization in 1988, which was expanded and consolidated in Cairo in 1994
      and Beijing in 1995. Consequently, adoption of the PAISM meant a significant step
      towards recognition of women's reproductive rights, even before gaining the
      various international forums for struggle.

PMID- 9594000
TI  - [Socio-cultural aspects of sexuality as obstacles to secondary prevention of
      cervical cancer]
AB  - The purpose of the study is to explore some characteristics of women's
      perspectives on their sexuality, as there is information that associates the
      population's sexual culture with the incidence of cervical cancer. The value of
      sexual pleasure, sexual activity after menopause, and ways of preventing cervical
      cancer are explored. Data were obtained from a group of women attending primary
      care clinics in Santiago, Chile, and who were at least a year late for their Pap
      smear. The value women ascribed to sexuality was more positive than in previous
      studies performed in Chile. Women want to learn more about their bodies, although
      a minority still have negative perspectives concerning their sexuality. These
      results offer health services the opportunity to carry out educational activities
      with the purpose not only of increasing the number of women who have Pap smears
      but also of improving their quality of life

PMID- 9594001
TI  - [Causes and factors associated with reproductive-age female mortality in Recife,
      Brazil]
AB  - Reproductive-age women, especially in developing countries, have failed to
      receive proper attention from the health care sector except during pregnancy.
      This study's objective was to contribute to the knowledge of the most frequent
      causes of death in this population group. The main purpose was to evaluate the
      occurrence and recording of deaths among women 10 to 49 years of age in Recife,
      Pernambuco, Brazil, during 1992 and 1993, and to identify and group the corrected
      causes of these deaths. It was a population-based descriptive study. After all
      death certificates eligible for the study were identified at the Health
      Secretariat of the State of Pernambuco, coding of the basic cause of death was
      performed. When necessary for its elucidation, a complementary investigation was
      also carried out at the hospital, autopsy service, and/or through an interview
      with the attending physician and a household visit. The 9th Revision of the ICD
      was used for coding the corrected basic cause of death. One thousand thirteen
      deaths of reproductive-age women were identified. The most frequent groups of
      causes of deaths were neoplasms, circulatory diseases, and external causes.
      Complications associated with pregnancy, delivery, and puerperium were the ninth
      most common cause of death in this group.

PMID- 9594002
TI  - [Association of prevalence of tubal ligation and sociodemographic characteristics
      of women and their partners in the State of Sao Paulo]
AB  - Brazil has a high prevalence of tubal ligation. The hypothesis that it indicates
      undercover birth control efforts specifically addressed to the poorest sector of
      Brazilian society has been raised. The purpose of this paper is to evaluate
      whether there are differences in rates of tubal ligation depending on
      socioeconomic status. Data were gathered from interviews with 1335 women 15-49
      years of age, of low or lower-middle socioeconomic status, carried out in 1991 in
      two regions of the State of Sao Paulo. The results showed an apparently higher
      prevalence of tubal ligation among women with less schooling,, but also among
      those living in better housing. However, after controlling for women's age, these
      associations disappeared, suggesting that they were explained by lower
      educational levels and greater economic resources of women of older age, where
      the latter factor is more heavily associated with a higher prevalence of tubal
      ligation. The complexity of the associations between socioeconomic status and
      tubal ligation are discussed, including the correlations between socioeconomic
      status and C-sections, which are in turn closely related to tubal ligation.

PMID- 9594003
TI  - [Regret by women following sterilization]
AB  - Female sterilization is the most widely used contraceptive method among Brazilian
      women, although it has not been provided by the National Health System. Due to
      its legal ambiguity, it has not been recommended by Medical Boards as an ethical
      procedure. A study in which 3,149 women were asked about contraceptive use was
      carried out in the Greater Sao Paulo Metropolitan Area between March and July
      1992. A total of 407 women under 40 years of age who had been submitted to
      sterilization at least one year prior to the interview were asked about their
      adjustment after the operation. Fifteen in-depth interviews with regretful women
      were analyzed in order to elucidate the nature of such feelings. The results
      include: adjustment after sterilization, provision of the sterilization
      procedure, knowledge of contraceptive methods, previous use of methods among
      sterilized women, and factors associated with regret. The qualitative results
      focus on the misinformation of sterilized women. Results indicate a need for
      regulating the procedure in order to ensure women's health, reproductive rights,
      and the fundamental principles of medical ethics.

PMID- 9594004
TI  - [Positive and negative aspects of Fallopian tube sterilization as viewed by
      sterilized women]
AB  - The objective of this paper is to point out the positive and negative aspects of
      female sterilization as seen by two groups of sterilized women in Florianopolis,
      Santa Catarina, Brazil, based on a sociological discussion of their present
      health status, evaluating the associations that they generally make with the fact
      that they have been sterilized. The first group included mostly housewives from a
      low-income neighborhood, while the second involved upper-middle-class female
      public employees, students, and university professors, totaling 40 women. Data
      were obtained through a structured questionnaire with open-ended questions.
      Information on social, economic, and demographic variables was recorded, along
      with subjective data associated with women's representations of the post
      sterilization period. We concluded that there was no consensus as to the
      consequences of sterilization, since a number of the women (11/40), mostly
      sterilized before the age of 30, perceived changes in their health status after
      surgery.

PMID- 9594005
TI  - [Psychosocial and cultural factors in the prevention and treatment of sexually
      transmitted diseases]
AB  - The article deals with the psychosocial and cultural dimensions of sexually
      transmitted diseases. Based on results from a qualitative study with lower-class
      males and females (young and adult) from a neighbourhood in the metropolitan area
      of Buenos Aires, the author discusses how lay beliefs (about symptoms,
      transmission, consequences) and norms regarding sexual matters and gender
      relations affect people's ability to consider themselves at risk and/or adopt
      preventive behaviors. Implications of research results for the design of
      culturally appropriate strategies to promote sexual and reproductive health are
      also provided.

PMID- 9594006
TI  - [Some elements for interpreting men's presence in reproductive health processes]
AB  - This study aims to identify analytical approaches to situate men in processes
      pertaining to reproductive health. We challenge the position that identifies them
      only as actors that can support improvements in the health of women and children.
      More recently there has been a concern over reshaping their role, as individuals
      who both reproduce and face risks to their reproductive organs, behaviors, and
      processes. One possibility for explaining men's presence in such processes is to
      identify their absence or presence as conditioning the consequences for women and
      children. The issue is to determine how they hamper or foster maternal health. A
      second possibility is to delve into the relational, social, and potentially
      conflictive nature of "sexualized" reproduction. This implies a new approach to
      the analysis of reproduction as a relational process, rather than as isolated
      events involving men and women, meanwhile recovering the respective
      specificities. The gender perspective is used to conceive of processes without
      denying the power dimension. Thus, a new approach is taken to sexuality,
      reproduction, and health in terms of interaction, in order to build clearer
      references with regard to the male population. We base our study on the approach
      attempting to build reflections on men as related to the dynamics of reproductive
      health.

PMID- 9594007
TI  - [Social representations of male sterilization. Vasectomy as viewed by
      professional counselors at the Men's Clinic in Bogota,Colombia]
AB  - Vasectomy service providers at the Clinica del Hombre (Men's Clinic) in Bogota,
      Colombia, construct their representations concerning male sterilization on the
      basis of biomedical discourse, their interaction with clinic users, and their own
      life experiences. During provision of such services, the counselors are the
      health professionals who have the closest contact with these clients of the
      clinic. Counselors are in charge of exploring their motivations in requesting the
      service, in addition to providing information allowing them to take a calm, sound
      decision. They also directly filter demand based on their experience, knowledge,
      and skills, in permanent negotiation between institutional criteria (number of
      children and gap between them, client's age, steadiness of couple's relationship,
      and conviction concerning the decision), and their perception and assessment of
      the client. An analysis of the counselors' representations of decision-making as
      pertaining to vasectomy indicates that it is a relatively simple and harmless
      procedure as well as a liberating option in terms of family planning.

PMID- 9594008
TI  - [Population policies and reproductive health in Paraguay]
AB  - The population's high growth rate, age profile, and geographical distribution
      have aroused increasing public concern in Paraguay. The country is involved in a
      moderate demographic transition, compatible with the consequences of modernity
      and the uneven rate of both social and economic changes. Reduction of mortality
      and the persistence of high birth rate patterns result in an age structure that
      consolidates demographic growth, with an increased focus on the dependent
      population. In the late 1960s the need for a systematic approach to population
      problems was perceived within the framework of economic planning. National
      governments had, and currently have, an ambivalent perception of this issue,
      since population growth is simply considered a positive factor. This concept
      results from an economic view of the consequences of a reduced domestic market in
      absolute terms. The lack of a Development Plan, the management deficit, and the
      shortage of training leave doubts as to the establishment of organically
      connected policies or programs concerning population.

PMID- 9594009
TI  - [Metaphorical/metonymical analysis of public health thinking vis-a-vis teenage
      pregnancy in the 1960s]
AB  - This article is an analytical essay on a historical moment in the formation of
      public health thinking vis-a-vis adolescent pregnancy: the 1960s. Its relevance
      lies in the fact that several assertions produced then still bear great influence
      on ideas and models concerning adolescent maternity in current public health
      thinking. From the technical and methodological point of view, one can assume two
      levels: an explicit one pertaining to the documentary record, consisting of
      messages clearly communicated by authors of scientific texts, and an implicit
      one, with elements that could only surface in text discourse through stylistic
      effects. Based on such assumptions, we explored the specialized literature using
      a metaphorical/metonymical analysis in search of such implicit dimensions.

PMID- 9594010
TI  - [Male perspectives on contraceptive methods]
AB  - Historically, family planning programs have targeted women almost exclusively.
      More recently it has become clear that men have a strong influence on their
      partners' use of contraception, either by opposing the use of any or one specific
      method, or by deciding that a woman has to either use a given method or be
      sterilized. In this context, our study aimed to evaluate the male perspective on
      the role of gender in the decision to use contraceptive methods and to have and
      raise children. The sample consisted of 776 males from a university in the State
      of Sao Paulo: 467 graduate students, 314 employees, and 129 teachers. A
      structured, previously tested questionnaire was used for the interviews. Data
      analysis is currently under way. The least familiar contraceptive methods were
      Billings (29.9%), injectables (35.4%), and jellies (57.8%). Some 80% of the
      interviewees mentioned other methods. The proportion of men who denied knowledge
      of any contraceptive method whatsoever was 1.6%. Our findings are similar to
      those of other authors.

PMID- 9594011
TI  - [The social sciences as discourse in reproductive health. The example of female
      climacteric]
AB  - Climacteric is constructed by medicine, lay knowledge, and the social sciences.
      This article examines the interrational models involving these different
      discourses and proposes that the contribution of the social sciences lies in a
      reformulation of the cognitive base of the health professions at an integrative
      level.

PMID- 9594012
TI  - [Progressive Catholic perspectives on reproductive health and rights: the
      political challenge of orthodoxy]
AB  - Catholics do not follow official Roman Catholic teachings on matters of sexuality
      and reproduction, including the position that contraception , even for married
      couples, is always evil, and that direct abortion , even to save a woman's life,
      is always illegal. Less well known is the extent of the Church's involvement in
      policy-making on these same issues. For example, it has forced the closing of in
      vitro fertilization (IVF) services from Poland to Uruguay. As the Church has
      never declared any of the dominant views, over time, regarding when a fetus
      becomes a person as a doctrine or dogma, there is no theological justification
      for the absolute condemnation of abortion. Neither is there a theory on "just
      abortion" similar to the "just war" that allows killing under certain
      circumstances. The enormous gap between the Church's positions and the views of
      worshippers has led Catholics to shape a workable and honorable sexual and
      reproductive ethic of their own The Church could make a positive contribution if
      it chose to accompany people on this quest rather than to raise roadblocks.

PMID- 9594013
TI  - [Reproductive health and population]

PMID- 9594014
TI  - Haemodynamic effects of the intravenous administration of growth hormone in
      anaesthetized pigs.
AB  - Administration of growth hormone in humans has been reported variably to affect
      arterial blood pressure and ventricular contractility. The present study was
      undertaken in anaesthetized pigs to establish whether increases in the blood
      levels of growth hormone primarily affect haemodynamic variables and to determine
      the mechanisms involved. In pigs anaesthetized with pentobarbitone sodium, left
      circumflex or anterior descending coronary blood flow was measured with an
      electromagnetic flowmeter. In a first group of 23 pigs, growth hormone
      administration (0.05 IU kg-1 i.v.) increased aortic blood pressure and reduced
      coronary blood flow when heart rate and aortic blood pressure were held constant.
      These responses were augmented by graded increases in plasma levels of growth
      hormone. The mechanisms of the above responses were studied in a second group of
      29 pigs and involved beta2-adrenergic receptors since they were abolished by
      propranolol or butoxamine but not by atropine, phentolamine or atenolol. The
      present study showed that administration of growth hormone in anaesthetized pigs
      primarily increased aortic blood pressure and vasoconstricted the coronary
      circulation. The mechanisms of these responses involved beta2-adrenoceptor
      effects.

PMID- 9594015
TI  - Accentuated antagonism by angiotensin II on guinea-pig cardiac L-type Ca-currents
      enhanced by beta-adrenergic stimulation.
AB  - To examine mechanism(s) underlying the accentuated antagonism by angiotensin II
      (A-II) on twitch tension, we recorded L-type Ca2+ currents (ICa,L) using
      conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes.
      ICa,L was recorded by a step-pulse protocol after eliminating K+ conductances
      (internal Cs+ plus tetraethylammonium chloride and K+-free extracellular
      solution). A-II (100 nM) did not affect basal ICa,L, but inhibited ICa,L that had
      been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The
      inhibitory action of A-II was concentration dependent (concentration eliciting
      50% inhibition 88+/-9 pM, n=41) and the ISO-enhanced component of ICa,L was
      completely blocked by A-II at concentrations above 10 nM. CV-11974 (500 nM), an A
      II type-1 receptor (AT1) antagonist, prevented the inhibitory action of A-II. Pre
      incubation with pertussis toxin (PTX) abolished the inhibitory effect of A-II. A
      II also inhibited the ICa, L enhanced by histamine (500 nM) and forskolin (1
      microM), but failed to affect ICa,L enhanced by intracellular cyclic adenosine
      monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT1
      receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate
      cyclase and partially explains the A-II-dependent accentuated antagonism of
      inotropy.

PMID- 9594016
TI  - Regulation of CFTR by protein phosphatase 2B and protein kinase C.
AB  - The activity of the CFTR Cl- channel is dependent on its phosphorylation status
      set by kinases and phosphatases. We report here that protein phosphatase 2B
      (PP2B) and protein kinase C (PKC) are potential regulators of the cystic fibrosis
      conductance regulator (CFTR). Treating CFTR-expressing 3T3 cells with either of
      the two specific PP2B blockers cyclosporin A (CsA, 1 microM) or deltamethrin (DM,
      30 nM) caused rapid activation of CFTR in cell-attached patches. As determined by
      noise analysis of multi channel patches, DM- or CsA-activated CFTR displayed
      gating kinetics comparable to those of forskolin-activated CFTR. After activation
      of CFTR by blocking PP2B, CFTR still inactivated. CFTR-mediated currents were, on
      average, 6.1 times larger when cells were stimulated by forskolin during PP2B
      block compared to stimulation by forskolin alone. This suggests that, in CFTR
      expressing 3T3 cells, a phosphorylation site of CFTR is regulated by cellular
      PKA, PP2B and another phosphatase. However, in the epithelial cell lines Calu-3
      and HT-29/B6, CsA and DM had no effect on CFTR activity in both cell-attached
      patch-clamp and transepithelial experiments. In contrast, when exogenous PP2B was
      added to patches excised from 3T3 or Calu-3 cells, PKA-activated CFTR currents
      were quickly inactivated. This indicates that free exogenous PP2B can inactivate
      CFTR in patches from both cell types. We propose that in order to regulate CFTR
      in an intact cell, PP2B may require a selective subcellular localization to
      become active. When excised patches were PKC-phosphorylated, the gating kinetics
      of CFTR were significantly different from those of PKA-phosphorylated CFTR.
      Addition of PP2B also inactivated PKC-activated CFTR showing the indiscriminate
      dephosphorylation of different phosphorylation sites by PP2B.

PMID- 9594017
TI  - Evidence for the presence of a Na+-H+ exchanger in the endolymphatic sac
      epithelium of guinea-pigs.
AB  - The intracellular pH (pHi) of epithelial cells from the endolymphatic sac (ES) of
      the guinea-pig was measured microfluorometrically with the pH-sensitive
      fluorescent dye, 2', 7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) to
      examine the presence of a Na+-H+ exchanger (NHE) in the ES epithelial cells. pHi
      recovery from acid loading with an NH4+-prepulse in a nominally HCO3-free
      solution was dependent on extracellular Na+ ([Na+]o) and was inhibited by
      amiloride and its analogue ethylisopropylamiloride (EIPA), suggesting that a
      decreased pHi induced by an acute acid load may be equilibrated by a NHE. In the
      steady-state, amiloride had no effect on pHi, indicating that the NHE activity is
      low at the resting pHi. However, the intracellular acidification induced by the
      removal of [Na+]o was inhibited by the simultaneous application of amiloride. H+
      efflux rate (JH, mean activity of NHE), which was calculated as the product of
      the recovery rate (dpHi/dt) from the acid loading and the intrinsic buffering
      capacity (betai) at the corresponding pHi, was decreased as pHi was increased.
      The concentration/response curve for the inhibition of initial JH by EIPA
      revealed an apparent 50% inhibitory constant (Ki ) of 0.85 microM. Kinetic
      analysis of initial JH as a function of [Na+]o revealed a Michaelis-Menten
      constant (Km) of 24.14 mM for Na+-dependent H+ efflux. The results indicate that
      NHE in the ES epithelium belongs to an amiloride-sensitive subtype.

PMID- 9594018
TI  - Novel protein kinase C, nPKC, inhibition of murine bumetanide-sensitive
      Na+,K+,2Cl- cotransporter BSC1 in Xenopus oocyte.
AB  - In vitro transcribed RNAs obtained for the absorptive type of Na,K, 2Cl
      cotransporter BSC1, isoform F, and either of three deletion mutants were injected
      into oocytes, while oocytes injected with water served as controls. Wild-type
      cRNA induced a bumetanide-sensitive Rb flux after 18 h which rose to a maximum of
      about 600 pmol . (h.oocyte)-1 during the next 24 h. This level of flux lasted for
      at least 31/2 days. All deletion mutants were either not expressed and/or were
      non-functional. The protein kinase C (PKC) activator phorbol 12-myristate 13
      acetate (PMA) eliminated the induced flux, with an apparent dissociation constant
      (aKi) of 6 nM. A 15 nM PMA-elicited inhibition of Rb flux was blocked by the PKC
      inhibitor calphostin C (200 nM) to approximately 80%, while PKC inhibitors
      staurosporine (40 nM) and Go6976 (50 nM) were ineffective. The phosphatase
      inhibitor okadaic acid (4.6 nM) did not influence PMA-induced flux inhibition.
      The PKC activator sn-1, 2-dioctanoyl glycerol (DOG), even at 2 microM, did not
      inhibit bumetanide-sensitive Rb influx. The induced Rb fluxes were not affected
      by PKA or PKG, as stimulation by either 0.5 mM dibutyryl-cAMP, 0.5 mM dibutyryl
      cGMP, 10 microM forskolin, and/or 0. 5 mM theophylline had no effect on
      bumetanide-sensitive Rb fluxes. Activating endogenous muscarinic receptors with
      20 microM acetylcholine had no effect on expressed BSC1 fluxes. The sensitivity
      to bumetanide of induced Rb flux had an aKi of around 70 nM. Attempts to follow
      the expression of BSC1 in plasma membranes with either immunoblotting or radio
      methionine pulse-chase were unsuccessful. We conclude that a PKC, likely of the
      novel type, nPKC, seems to be involved in PMA-induced reduction of expressed BSC1
      and/or its ion transport function.

PMID- 9594019
TI  - Dynamics of Ca2+i and pHi in Ehrlich ascites tumor cells after Ca2+-mobilizing
      agonists or exposure to hypertonic solution.
AB  - Intracellular free calcium concentration ([Ca2+]i) and intracellular pH (pHi)
      were monitored in Ehrlich ascites tumor cells using Fura-2 or 2',7',-bis-(2
      carboxyethyl)-5,6-carboxyfluorescein (BCECF), or both probes in combination. An
      increase in [Ca2+]i induced by thrombin or bradykinin, agonists known to elicit
      transient cell shrinkage in these cells, evoked a transient intracellular
      acidification, followed by an alkalinization. The latter was due to activation of
      a Na+/H+ exchanger and was inhibited under conditions preventing agonist-induced
      cell shrinkage without preventing the increase in [Ca2+]i. In contrast, a
      smaller, slower increase in [Ca2+]i elicited by thapsigargin did not cause cell
      shrinkage, and did not activate the Na+/H+ exchanger. Exposure to hypertonic
      solution was not associated with an increase in [Ca2+]i, but elicited an
      intracellular alkalinization similar to that induced by thrombin or bradykinin,
      via activation of the Na+/H+ exchanger. Thus, activation of the exchanger by the
      Ca2+-mobilizing agonists is suggested to be secondary to the cell shrinkage
      induced by these compounds. NH4Cl-induced intracellular alkalinization resulted
      in an increase in [Ca2+]i, apparently via stimulation of Ca2+ influx, whereas
      shrinkage-induced intracellular alkalinization did not stimulate Ca2+ influx.
      Thus, cell shrinkage appears to inhibit the Ca2+ influx otherwise resulting from
      alkalosis. In agreement with that notion, thapsigargin-induced Ca2+ influx was
      inhibited by cell shrinkage.

PMID- 9594020
TI  - Fuel metabolism during ultra-endurance exercise.
AB  - Cyclists either ingested 300 ml 100 g/l U-[14C] glucose solution every 30 min
      during 6 h rides at 55% of VO2max (n=6) or they consumed unlabelled glucose and
      were infused with U-[14C] lactate (n=5). Maintenance of euglycaemia limited rises
      in circulating free fatty acids, noradrenaline and adrenaline concentrations to
      0.9+/-0. 1 mM, 27+/-4 nM and 2.0+/-0.5 nM, respectively, and sustained the
      oxidation of glucose and lactate. As muscle glycogen oxidation declined from
      100+/-13 to 71+/-9 micromol/min/kg in the last 3 h of exercise, glucose and
      lactate oxidation and interconversion rates remained at approximately 60 and 50
      and at about 4 and 5 micromol/min/kg, respectively. Continued high rates of
      carbohydrate oxidation led to a total oxidation of around 270 g glucose, 130 g
      plasma lactate and 530 g muscle glycogen. Oxidation of some 530 g of muscle
      glycogen far exceeded the predicted (about 250 g) initial glycogen content of the
      active muscles and suggested that there must have been a considerable diffusion
      of unlabelled lactate from glycogen breakdown in inactive muscle fibres to
      adjacent active muscle fibres via the interstitial fluid that did not equilibrate
      with 14C lactate in the circulation.

PMID- 9594021
TI  - A transient dilatation of pressurised rat cerebral arteries during rapid pressure
      increases is mediated by nitric oxide.
AB  - In pressurised resistance arteries in vitro, rapid pressure increases cause a
      transient "peak" dilatation, followed by a myogenic constriction. The mechanism
      of transient dilatation was investigated in isolated rat cerebral arteries in
      vitro using pressure myography. The peak increased with the amplitude of the
      pressure step. A near-maximal dilatation to 118+/-1.6% (SEM, n=20) of the
      diameter at 30 mmHg was produced by pressure steps from 30 to 75 mmHg. Nomega
      nitro-l-arginine methyl ester (L-NAME, 20 microM) depressed the peak at the onset
      of a 30 to 75 mmHg pressure step to 49.8+/-14% of the control (n=6; P=0.04). D
      NAME (20 microM) had no significant effect (82.1+/-13%; n=4; P=0.13). L-Arginine
      (400 microM) enhanced the peak (164+/-17% of control; n=8; P=0.01). Oxadiazolol
      (4,3-a) quinoxalin-1-one (ODQ, 2 microM) depressed the peak to 33.2+/-12% of
      control (n=5; P=0.012). 6-Anilino-5, 8-quinolinedone (LY 83583, 10 microM)
      depressed the peak to 18.8+/-2. 9% of control (n=3; P=0.01). Removing the
      endothelium decreased the peak to 15.3+/-11% of control (n=3; P=0.04). In
      conclusion, in rat cerebral arteries, the initial dilatation at the onset of a
      rapid step increase in pressure is an active dilatation involving endothelial NO
      release.

PMID- 9594022
TI  - Hypertonic cell shrinkage reduces the K+ conductance of rat colonic crypts.
AB  - It has previously been shown in studies of a renal epithelial cell line that
      nonselective cation (NSC) channels are activated by exposure to hypertonic
      solution. We have also found such channels in excised patches of colonic crypt
      cells. They require high Ca2+ activities on the cytosolic side and a low ATP
      concentration for their activation and have not been recorded from cell-attached
      patches of colonic crypts. We examine here whether this type of channel is
      activated by hypertonic cell shrinkage. Bath osmolality was increased by addition
      of 25, 50 or 100 mmol/l mannitol. Cell-attached and whole-cell patch recordings
      were obtained from rat base and mid-crypt cells. In whole-cell recordings we
      found that addition of 50 or 100 mmol/l mannitol depolarized these cells
      significantly from -78+/-2.0 to -66+/-3.8 mV (n=22) and from -78+/-1. 3 to -56+/
      2.6 mV (n=61), respectively, and reduced the whole-cell conductance from 20+/-8.0
      to 14+/-6.6 nS (n=7) and from 20+/-3.0 to 9.8+/-1.6 nS (n=19), respectively. In
      cell-attached patches K+ channels with a single-channel conductance of
      approximately 16 pS were found in most recordings. The activity of these channels
      (NxPo, N=number, Po=open channel probability) was reduced from 2.08+/-0.37 to
      0.98+/-0.23 (n=15) by the addition of 50 mmol/l mannitol and from 1.75+/-0.26 to
      0.77+/-0.20 (n=12) by 100 mmol/l mannitol. No NSC channel activity was apparent
      in any of these recordings. Previously we have shown that the 16-pS K+ channel is
      controlled by cytosolic Ca2+ ([Ca2+]i). Therefore we measured [Ca2+]i by the fura
      2 method and found that hypertonic solution reduced [Ca2+]i significantly (n=16).
      These data indicate that exposure of rat colonic crypts to hypertonic solutions
      does not activate NSC channels; [Ca2+]i falls in hypertonic solution leading to a
      reduction in the value of K+ channel NxPo, a reduced whole-cell conductance and
      depolarization of mid-crypt cells. These processes probably assist volume
      regulation inasmuch as they reduce KCl losses from the cell.

PMID- 9594023
TI  - Granulocyte-colony stimulating factor inhibits TNFalpha production in a human
      hepatoma cell line.
AB  - The syndrome of cachexia associated with malignant diseases can be in part
      attributed to the effects of tumour necrosis factor alpha (TNFalpha) which itself
      is produced by a variety of tumour cells. We have recently reported that the
      human hepatoma cell line HepG2 expresses the TNFalpha gene and releases
      biologically active TNFalpha protein after stimulation with interleukin-1beta (IL
      1beta). Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein necessary
      for the proliferation and differentiation of neutrophil progenitor cells in the
      bone marrow. In addition G-CSF has been reported to exert anti-inflammatory
      effects. In our study we tested the effect of recombinant human G-CSF (rhG-CSF)
      on TNFalpha production in HepG2 cells. It could be shown that rhG-CSF (250 U/ml)
      significantly reduced IL-1beta-induced (300 pg/ml) TNFalpha gene expression after
      1-h and 3-h incubation periods (TNFalpha mRNA concentrations were: 8.8+/-2.1
      amol/ microg total RNA after a 1-h incubation with IL-1beta versus 3.8+/-1.3
      amol/ microg total RNA after a 1-h incubation with IL-1beta + rhG-CSF and 13.8+/
      2.2 amol/ microg total RNA after a 3-h incubation with IL-1beta versus 8.8+/-2. 1
      amol/ microg total RNA after a 3-h incubation with IL-1beta + rhG-CSF). From
      these data we conclude that rhG-CSF is a potent inhibitor of cytokine-induced
      TNFalpha production by tumour cells. Therefore, treatment of patients with
      malignant diseases with rhG-CSF might represent a useful tool to improve the
      tumour-associated cachexia.

PMID- 9594024
TI  - Effects of temperature on human L-type cardiac Ca2+ channels expressed in Xenopus
      oocytes.
AB  - Temperature normally affects peak L-type Ca2+ channel (CaCh) current with a
      temperature coefficient (Q10) of between 1.8 and 3.5; in cardiomyocytes
      attenuating protein kinase A activity increases Q10 whilst activating it lowers
      Q10. We examine temperature effects using cloned human cardiac CaChs expressed in
      Xenopus oocytes. Peak inward currents (IBa) through expressed CaChs (i.e. alpha1C
      alpha2/deltaa beta1b) exhibited a Q10 of 5.8+/-0.4 when examined between 15 and
      25 degreesC. The nifedipine-sensitive IBa exhibited a higher Q10 of 8.7+/-0.5,
      whilst the nifedipine-insensitive IBa exhibited Q10 of 3.7+/-0.3. Current/voltage
      (I/V) relationships shifted to negative potentials on warming. Using instead a
      different CaCh beta subunit isoform, beta2c, gave rise to an IBa similar to those
      expressed using beta1b. We utilized a carboxyl deletion mutant, alpha1C
      Delta1633, to determine the temperature sensitivity of the pore moiety in the
      absence of auxiliary subunits; IBa through this channel exhibited a Q10 of 9.3+/
      0.3. However, the Q10 for macroscopic conductance was reduced compared to that of
      heteromeric channels; decreasing from 5.0 (i.e. alpha1C alpha2/deltaa beta1b) and
      3.9 (i.e. alpha1C alpha2/deltaa beta2c) to 2.4 (alpha1C-Delta1633). These
      observations differ markedly from those made in studies of cardiomyocytes, and
      suggest that enhanced sensitivity may depend on the membrane environment, channel
      assembly or other regulatory factors.

PMID- 9594025
TI  - pH-regulatory mechanisms in in vitro perfused rectal gland tubules of Squalus
      acanthias.
AB  - Isolated in vitro perfused rectal gland tubules (RGT) were preincubated with the
      pH-sensitive dye 2', 7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and pH
      regulatory mechanisms were studied. A reduction of bath Cl- concentration from
      269 to 6 mmol/l increased the fluorescence ratio 488/436 [corresponding to
      cytosolic pH (pHi)] slightly but significantly (n=10). Depolarization by Ba2+ (1
      mmol/l) or a bath solution containing 30 mmol/l K+ (n=4-6) increased the
      fluorescence ratio (pHi). These data suggest that HCO3- uptake and/or H+
      extrusion is dependent on Cl- and/or voltage. A reduction of bath Na+ from 278 to
      5 mmol/l reduced the ratio significantly (n=3). Addition of trimethylamine
      (Trima+, 20 mmol/l) alkalinized cytosolic pH (n=7). Similarly, addition of NH4+
      (20 mmol/l) led to an initial alkalinization and a strong acidification when NH4+
      was removed (n=59). The initial pHi-recovery rates after NH4+ removal were
      quantified and the responsible H+ extrusion and/or HCO3- import systems were
      examined. The recovery was almost completely abolished when the extracellular Na+
      concentration was reduced to 5 mmol/l. In the presence of normal Na+, recovery
      was slower in the absence as compared to the presence of HCO3- (n=5). It was
      inhibited by 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) (0.5
      mmol/l, n=11) in the presence of HCO3- and in the absence of HCO3- by the Na+/H+
      exchange blocker HOE694 (0.5 mmol/l, n=6). These data suggest that acid extrusion
      probably occurs by basolateral Na+-2HCO3-/Cl- exchange in the presence of HCO3-
      and by basolateral Na+/H+ exchange in the absence of HCO3-. Luminal perfusion
      with a solution containing a low Cl- concentration (6 mmol/l) increased the
      fluorescence ratio (pHi) (n=5). The ratio (pHi) was further increased and pH
      recovery further delayed by basolateral addition of Trima+ (20 mmol/l, n=3).
      These data suggest that the HCO3-/Cl- exchanger is present in the luminal
      membrane. Luminal HCO3-/Cl- exchange and basolateral Na+-2HCO3-/Cl- exchange may
      work in tandem to secrete HCO3- and exchange it for luminal Cl-.

PMID- 9594026
TI  - The role of mast cells and histamine in leukocyte-endothelium interactions in
      four rat strains.
AB  - The objective of the present study was to determine the role of mast cells and
      histamine in leukocyte-endothelium interactions in mesenteric venules of four rat
      strains: Brown Norway, Lewis, Sprague-Dawley and Wistar. Intravital microscopy
      showed that the mast cell stabilizer cromoglycate (5 mg/kg i.v. just before
      exteriorization of the mesentery) did not affect the baseline level and velocity
      of leukocyte rolling in any of the four strains. This finding is in agreement
      with the observation that cromoglycate pretreatment only slightly influenced mast
      cell degranulation in all strains except the Brown Norway. After mast cell
      stabilization, only in Sprague-Dawley did topical administration of histamine
      (10(-4) M) result in a significant increase in the level of leukocyte rolling and
      a decrease in the rolling velocity compared with the time control. Histamine
      induced leukocyte adhesion only in the Brown Norway strain. In conclusion, the
      hypothesis presented in other studies, that degranulation of mast cells, and more
      specifically the release of histamine, is of major importance for the induction
      of leukocyte-endothelium interactions in rat mesenteric venules is not generally
      applicable; the present study shows a clear strain dependency.

PMID- 9594027
TI  - Calcium-contraction relationship in rat mesenteric arterial smooth muscle.
      Effects of exogenous and neurogenic noradrenaline.
AB  - We evaluated the relationship between intracellular calcium concentration
      ([Ca2+]i) and vasoconstriction during the presence of exogenous noradrenaline
      (NA) and sympathetic nerve stimulation. An imaging technique was used to
      determine calcium/tension relationships in isolated rat mesenteric resistance
      arteries that had been mounted for recording of isometric tension development and
      loaded with Fura-2/AM. Experiments were performed after depletion of vasodilator
      neuropeptides and in the continuous presence of 1 microM propranolol, 3 microM
      indomethacin, and 30 microM nitro-l-arginine. NA (10 microM) was shown first to
      induce a further increase in tension, but not [Ca2+]i, during the contraction
      induced by 125 mM K+. Subsequently, calcium/tension relationships were determined
      during stimulation with graded increases in extracellular [K+] (5. 9-125 mM K+),
      cumulative administration of NA (0.2-10 microM) and electrical field stimulation
      of perivascular nerves (EFS, 1-16 Hz). A basal calcium/tension relationship
      without the calcium-sensitizing property of NA was constructed using a cumulative
      concentration/response curve of 5.9-125 mM K+ in arteries after prior exposure to
      the irreversible alpha-adrenoceptor antagonist phenoxybenzamine (POB). K+ series
      before and during alpha-blockade were also studied using the combination of the
      alpha1-antagonist prazosin and alpha2-antagonist yohimbine yielding comparable
      results as with POB. Calcium/tension curves obtained in the presence of NA, K+
      and during EFS all were shifted to the left compared with the basal condition and
      all showed a similar slope indicating that neurogenically released NA is equally
      capable of inducing calcium sensitization in smooth muscle of mesenteric
      resistance arteries as exogenously applied NA. In the presence of exogenous and
      endogenous NA we not only observed an elevated contractile response for a given
      increase in [Ca2+]i, but also an attenuated rise in [Ca2+]i for a given intensity
      of stimulation. This suggests that the agonist-induced calcium-sensitization is
      accompanied by a reduction of the rise in [Ca2+]i.

PMID- 9594028
TI  - Role of the cytoskeleton in stimulation of Na+ channels in A6 cells by changes in
      osmolality.
AB  - Permeable supports with A6 cell monolayers were mounted in an Ussing chamber and
      bilaterally bathed with Ringer solution at room temperature. Short-circuit
      current (Isc) was recorded continuously, and noise analysis revealed microscopic
      channel current characteristics. Our investigation focuses on the stimulation of
      apical Na+ entry caused by exposing the serosal surface of the A6 cell monolayers
      to hyposmotic Ringer solution. To evaluate the possible role of the cytoskeleton
      in the regulation of Na+ channels in response to a change in osmolality we used
      four different experimental approaches. In the control group, which were not
      exposed to any cytoskeleton-influencing drugs, there was a 1.5-fold increase in
      Isc and in the number of open Na+ channels after osmotic stimulation. For the
      second group cytochalasin D (0.1 microg/ml) was present on the serosal side
      during the experiments. Neither Isc nor the number of open Na+ channels increased
      after osmotic stimulation. In the third group colchicine (0.2 mM) or nocodazole
      (20 microM) was present on the serosal side, which resulted in 1.8-fold and 1.5
      fold increases in Isc as well as 3-fold and 2-fold increases in the number of Na+
      channels, respectively. In the fourth experimental group erythro-9-(2-hydroxy-3
      nonyl) adenine hydrochloride (EHNA, 0.5 mM), a dynein inhibitor, was present on
      the serosal side. In this group Isc decreased to about 0.4 microA/cm2, and
      subsequent application of amiloride abolished Isc completely. Under hyposmolar
      conditions EHNA abolished entirely the sensitivity of Isc to the osmotic
      challenge. Because of the EHNA-induced down-regulation of Isc, the density of
      apical Na+ channels in this experimental group could not be determined. These
      results show that the cytoskeleton is dominantly involved in osmotic channel
      regulation at the apical membrane, and that actin filaments, microtubules and
      molecular motors are involved in the recruitment of additional Na+ channels.

PMID- 9594029
TI  - Cellular site of active K absorption in the guinea-pig distal colonic epithelium.
AB  - The mammalian distal colon, which is composed of different cell types, actively
      transports Na, K and Cl in absorptive and K and Cl in secretory directions. To
      further characterize the K absorption process and to identify the cells involved
      in K absorption, unidirectional Rb fluxes and luminal Rb uptake into different
      epithelial cell types were determined in isolated guinea-pig distal colon. Net Rb
      absorption (1.5-2.5 micromol.h-1.cm-2) was not influenced by inhibition of Na
      transport with amiloride or by incubating both sides of the epithelium with Na
      free solutions, but was almost completely abolished by luminal ouabain,
      ethoxzolamide or by incubating both sides of the epithelium with Cl-free
      solutions. Luminal Rb uptake, blockable by luminal ouabain, preferentially
      occurred in columnar surface and neck cells, to a lesser extent in surface goblet
      cells and to an insignificant degree in lower crypt cells. Employing a luminal Rb
      Ringer (5.4 mM Rb) the Rb concentration increased within 10 min in columnar
      surface and neck, surface goblet and lower crypt cells to 70, 32 and about 10
      mmol. kg-1 wet weight, respectively. The presence of 5.4 mM K in the luminal
      incubation solution reduced Rb uptake almost completely indicating a much higher
      acceptance of the luminal H-K-ATPase for K than for Rb. The increase in Na and
      decrease in K concentrations in surface and neck cells induced by luminal ouabain
      might indicate inhibition of the basolateral Na-K-ATPase or drastic enhancement
      of cellular Na uptake by the Na-H exchanger. Bilateral Na-free incubation did not
      alter Rb uptake, but bilateral Cl-free incubation drastically reduced it.
      Inhibition of net Rb absorption by ethoxzolamide and inhibition of both Rb
      absorption and Rb uptake by bilateral Cl-free incubation support the notion that
      cellular CO2 hydration is a necessary prerequisite for K absorption and that HCO3
      leaves the cell via a Cl-HCO3 exchanger. Since ouabain-inhibitable
      transepithelial Rb flux and luminal Rb uptake rate by surface and neck cells were
      about the same, Rb(K) absorption seems to be accomplished mainly by columnar
      surface cells.

PMID- 9594030
TI  - Evidence for interference of vitamin D with PTH/PTHrP receptor expression in
      opossum kidney cells.
AB  - Vitamin D counters the phosphaturic action of parathyroid hormone (PTH) in rats
      in vivo. The present study was undertaken to examine this interaction using
      monolayers of Opossum kidney (OK) cells. 32P uptake, cAMP generation, PTH/PTHrP
      receptor mRNA expression and intracellular Ca2+ [Ca2+]i were measured in (1)
      control cells, (2) cells exposed to PTH, (3) cells pretreated with 1, 25
      dihydroxyvitamin D3 [1,25(OH)2D3], and (4) 1,25(OH)2D3-pretreated cells exposed
      to PTH. 32P uptakes were in (1) 5.00+/-0.20 (mean +/-SE), in (2) 2.30+/-0.14
      (P<0.001 versus group 1), in (3) 4.80+/-0. 24 (P NS versus group 1) and in (4)
      3.70+/-0.20 (P<0.001 versus group 2) nmol Pi/(mg.prot 10 mm). cAMP levels were in
      (1) 10+/-3, in (2) 210+/-8, in (3) 12+/-4, and in (4) 122+/-12 pmol cAMP/mg
      protein (P<0.001 versus group 2). PTH/PTHrP receptor mRNA expression was in
      relative units: (1) 100+/-0, (2) 99.5+/-6.2, (3) 68.7+/-2.6 (P<0.001 versus group
      1), and (4) 34.8+/-3.3 (P<0.001 versus group 1). In groups 2 and 4 PTH induced
      equal transient increments in [Ca2+]i. These experiments demonstrate that the
      effect of vitamin D on phosphate transport is associated with a commensurate
      diminution in PTH/PTHrP receptor gene expression and PTH-induced cAMP formation
      but not with Ca2+ transients. Vitamin D per se does not affect 32P uptake or cAMP
      generation while it slightly decreased PTH/PTHrP receptor gene expression. These
      observations demonstrate that: (1) 1. 25(OH)2D3 directly antagonizes the effects
      of PTH on 32P uptake in OK cells, (2) this effect is mediated via inhibition of
      PTH-induced activation of AC/cAMP system, (3) the diminution in PTH-induced cAMP
      formation may stem at least in part from a decrease in the expression of
      PTH/PTHrP receptor mRNA.

PMID- 9594031
TI  - Analysis of muscle adaptations to terrestrial stepping in the Urodelan amphibian
      Pleurodeles waltlii.
AB  - The changes of myosin isoform pattern and of its associated light chains in
      relation to the myosin ATPase profile were analysed in different muscles of the
      hypothyroidian amphibian Pleurodeles waltlii submitted to terrestrial stepping,
      using electrophoretic and histochemical techniques. These changes were specific
      to the muscle type but appeared globally characterized by a type-IIB to type
      IIA/I fibre transition associated with a transition from fast to intermediate
      and/or slow myosin isoforms. These results are similar to the effects of
      endurance training on locomotor muscles of mammals. The diaphragm of experimental
      animals was also characterized by a complete disappearance of the larval myosin
      isoforms which were detected in the diaphragm of control animals. The myosin
      pattern of ventricular muscle did not change following terrestrial stepping. This
      work indicates that thyroid hormone does not regulate the muscle adaptations that
      occur following terrestrial stepping and suggests a more complex mechanism of
      regulation in which innervation could be implicated.

PMID- 9594032
TI  - Small-volume and rapid extracellular solution exchange around Xenopus oocytes
      during voltage-clamp recordings.
AB  - A novel method for micro extracellular perfusion of Xenopus oocytes has been
      designed in order to minimise the amount of test solution required for drug
      applications during two-microelectrode voltage-clamp experiments. Voltage-clamp
      experiments on oocytes are performed in a glass-covered microbath without
      continuous perfusion. The microelectrodes access the oocytes via two small
      openings in the glass cover. Test solutions are applied to a funnel at the
      chamber inflow and the chamber volume is subsequently exchanged by operating a
      suction pump connected to the chamber outflow. Only 50 microl of drug- or
      neurotransmitter-containing solution is required for bath application. In
      addition, the new "funnel application technique" enables quick and timed
      applications of drugs or neurotransmitters to Xenopus oocytes within 200-400 ms.

PMID- 9594033
TI  - Preface 
AB  - Copyright

PMID- 9594034
TI  - The clinical management and results of surgery for acute cholecystitis.
AB  - The laparoscopic approach to acute cholecystitis is not only feasible, but it is
      also a cost-effective, safe, and beneficial treatment option in selected
      patients. Patients undergoing laparoscopic surgery for acute cholecystitis seem
      to enjoy the same benefits of diminished pain and shorter hospitalization as
      those patients undergoing an elective laparoscopic cholecystectomy. The
      complication rates are also comparable with those for an open cholecystectomy. An
      early laparoscopic cholecystectomy within 4 days of the onset of symptoms has
      been shown to reduce the number of major complications and conversion rate, thus
      resulting in a decreased hospital stay. A low threshold for conversion to
      laparotomy also seems to be an important factor in maintaining a low incidence of
      operative complications. The conversion to laparotomy is therefore considered to
      be a good surgical option for experienced surgeons. Patients who are in the high
      risk category or who have severe disease are best managed initially by
      gallbladder drainage unless they have perforated disease, which thus requires an
      emergency laparotomy.

PMID- 9594035
TI  - The difficult cholecystectomy: problems during dissection and extraction.
AB  - All surgeons will encounter difficult cholecystectomies. Many trying and
      untenable situations can be prevented or made easier by the cautious surgeon who
      has a carefully thought-out plan for each potential problem. Step-by-step, this
      article addresses the arduous challenges that may be faced beginning with
      diagnosis and continuing through the operative procedure including the decision
      to operate, the best intervention, abdominal entry, dealing with common duct
      stones, intraoperative cholangiography, exposure of the biliary anatomy,
      avoidance of bleeding or common duct injury, spilled stones, and postoperative
      bile collection. Each problem is addressed with emphasis on prevention and
      management.

PMID- 9594036
TI  - Access problems in laparoscopic cholecystectomy: postoperative adhesions,
      obesity, and liver disorders.
AB  - In the decade since the clinical arrival of laparoscopic cholecystectomy, there
      have been gratifying improvements in imaging technology and instrumentation, and
      innovative techniques have evolved. Laboratory-simulator devices are available
      for basic skills exercises and can at least reasonably mimic the appearance of
      the gallbladder and some other organs or anatomic regions. Unfortunately, there
      is no satisfactory method to practice dealing with certain structural
      abnormalities or disease processes. Because of that, some operations will be
      particularly difficult and the outcomes will be favorable only with careful
      planning and capable execution. The experiences and skill level of the surgeon
      can be enhanced by appropriate mental preparation. As a result, the surgeon will
      have the opportunity to accomplish the task, both laparoscopically and safely,
      under circumstances that initially were thought to be inappropriate or impossible
      for laparoscopy.

PMID- 9594037
TI  - The difficult cholecystectomy: problems related to concomitant diseases.
AB  - The difficult gallbladder is the most common "difficult" laparoscopic surgery
      performed by general surgeons. It is also "potentially" the one that places the
      patient at significant risk. This article reports on our first 1,900 laparoscopic
      cholecystectomies. With this report, it is the desire of the authors to share our
      experiences and lessons learned from more than 300 difficult gallbladder cases.
      We surgeons must strive for no bile duct injuries. If certain principles are
      followed, the surgeon will be able to improve his or her completion rate and
      decrease (if not eliminate) bile duct injuries. First and foremost is to know
      when to convert to open. Performance of fluorocholangiography to define anatomy
      is also very helpful in avoidance of bile duct injury. The laparoscopic surgeon
      should start with simple cases before "graduating" to more complex cases. Lastly,
      the ability to suture and knot tie is key in performing advanced procedures. This
      skill will allow completion of cases that otherwise would have to be converted to
      traditional surgery.

PMID- 9594038
TI  - Alternative methods for management of the complicated gallbladder.
AB  - Laparoscopic cholecystectomy is the procedure of choice for symptomatic
      cholelithiasis. However, in the presence of acute cholecystitis, 10% to 15% of
      patients face conversion to laparotomy. Alternatives to conventional therapy may
      therefore help to improve the clinical outcome of patients with complicated
      gallbladder disease. In selecting patients for alternative therapies,
      preoperative and intraoperative factors must be considered. Preoperative factors
      include the severity of biliary disease and preexisting medical risk factors;
      whereas intraoperative factors include conditions at the time of surgery that
      make dissection difficult or unsafe. Alternative therapies provide the least
      invasive management to safely temporize or definitively treat the acute
      condition. These alternatives include percutaneous cholecystostomy alone or
      followed by laparoscopic cholecystectomy, laparoscopic cholecystostomy followed
      by laparoscopic cholecystectomy, laparoscopic subtotal cholecystectomy,
      endoscopic retrograde cannulation of the gallbladder, and extracorporeal
      shockwave lithotripsy. By appropriate selection of the initial therapeutic
      approach, the surgeon may ultimately improve the clinical outcome in these
      complicated patients.

PMID- 9594039
TI  - The management of gallbladder cancer: before, during, and after laparoscopic
      cholecystectomy.
AB  - Carcinoma of the gallbladder is a rare disease, but when encountered in the
      patient undergoing laparoscopic cholecystectomy, it can pose a number of
      dilemmas. Familiarity with the risk factors for malignant gallbladder disease can
      help identify patients in whom more extensive preoperative evaluation is
      warranted. When carcinoma is identified preoperatively, cholecystectomy should be
      performed as an open procedure. If malignancy is encountered unexpectedly during
      laparoscopic cholecystectomy, the procedure should be converted to an open
      resection to allow for appropriate evaluation of the stage of disease and
      appropriate surgical management. Most commonly, malignancy is identified
      postoperatively, only after pathological examination of the resected gallbladder.
      Except in rare circumstances, open reoperation is necessary to achieve an
      adequate curative resection. The current concerns about port site recurrence and
      carcinomatosis after laparoscopic resection of a gallbladder carcinoma are
      unwarranted based on current published data. The role of prophylactic excision or
      irradiation of port sites is uncertain based on current understanding of the
      biological behavior of the disease.

PMID- 9594040
TI  - Laparoscopic cholecystectomy in pregnancy: a review of published experiences and
      clinical considerations.
AB  - Symptomatic biliary disease during pregnancy may have serious consequences for
      both the mother and the fetus. Laparoscopic cholecystectomy was felt initially to
      be contraindicated in pregnancy, but clinical experience accumulated since 1991
      has been extremely favorable. Specialists in the areas of anesthesiology,
      obstetrics and laparoscopic surgery should continue to carefully monitor and
      analyze practices and outcomes of laparoscopic cholecystectomy during pregnancy.
      At the present time, there is no consensus regarding several management issues,
      such as optimal pressure limits for insufflation. Nevertheless, the reported
      results are quite encouraging and may foretell an improvement in patient care for
      this special population as dramatic as that achieved by laparoscopic
      cholecystectomy in others.

PMID- 9594041
TI  - Bile duct injury: management options during and after gallbladder surgery.
AB  - Proper management of iatrogenic bile duct injuries is mandatory to avoid
      immediate or late life threatening sequelae. Results of surgery depend mainly on
      the type of injury, the detection of the injury, and the timing of the surgery.
      Lesions detected during cholecystectomy should be repaired immediately,
      preferably with an end-to-side biliary anastomosis, a Roux-en-Y bilio-enteric
      anastomosis, or by the insertion of a T-tube. Bile duct injuries detected in the
      postoperative phase require a multidisciplinary approach and an algorithm for
      treatment of each type of lesion is proposed. In bile peritonitis with biliary
      obstruction and/or transection and in tight long strictures, which develop
      several months after cholecystectomy, a Roux-en-Y hepatico-jejunostomy is the
      most commonly performed operation. Other surgical techniques include a "mucosal
      graft" procedure and intrahepatic biliary enteric anastomoses, which may be
      required in difficult high-biliary lesions. Endoscopy and/or interventional
      radiology offer the best treatment options in bile duct leaks and in short ductal
      strictures that involve less than 50% of the bile duct lumen. In these injuries,
      surgical management should be performed only in the failure of nonsurgical
      methods. Because these lesions involve complicated biliary surgery, therapeutic
      endoscopy, and interventional radiology, treatment should be performed where
      there is expertise in all three areas.

PMID- 9594043
TI  - An enzymatic method for the determination of free fatty acids in serum/plasma.
AB  - Estimation of serum free fatty acids (FFA) in serum based on the formation of
      inorganic phosphate has been simplified by eliminating complex stages. The
      principle of the present method is based on breakdown of pyrophosphate, formed by
      thioesterification of free fatty acids with ATP and CoA with the aid of acyl-CoA
      synthetase (EC 6.2.1.3) to inorganic phosphate. This is measured using the
      reaction with molybdate. The reaction equations are as follows: [formula: see
      text] The recovery of free fatty acids was 96%. The interferences of citrate,
      phosphatidylserine, succinate, ascorbic acid and lecithin were between 0.5 and
      2%. The correlation between the new enzymatic and the classic enzymatic method
      was 0.966. The lower detection limit was 0.018 mmol/l. The method was linear
      between 0.02 and 2.0 mmol/l. The within-assay and between-assay imprecision (CV)
      of control sera was 5.5% and 8%, respectively.

PMID- 9594044
TI  - Specificity of cardiac troponins I and T in renal disease.
AB  - We investigated and compared serum levels of cardiac troponins I(cTnl) and
      cardiac troponin T (cTnT) in 85 renal patients (chronic renal impairment n = 23,
      continuous ambulatory peritoneal dialysis n = 20, hemodialysis n = 42). Patients
      with the following conditions were excluded: myocardial infarction, angina
      pectoris, liver disease, malignant neoplasms, enforced physical activity,
      skeletal muscle trauma, myositis, rhabdomyolysis and seizures. Troponin T was
      measured by the second generation cTnT-ELISA with a cut-off value = 0.1
      microgram/l. Troponin I was measured by a cTnI immunoassay analyser with a cut
      off value = 2.0 micrograms/l. Additionally, creatine kinase (CK), CK-MB activity,
      CK-MB mass concentration and myoglobin levels were measured. Specificity was
      determined as the fraction of true-negative cases compared to the total number of
      false-positive and true-negative cases. Specificity for cTnT was 96% [78-100] in
      patients with renal impairment (creatinine > 150 mumol/l), 95% [75-100] in
      continuous ambulatory peritoneal dialysis patients, but in hemodialysis patients
      it was 75% [53-92] for short-term hemodialysis (< 1 year) and 46% [24-68] for
      long-term hemodialysis (> 1 year). There was a weak correlation between cTnT
      levels and duration of hemodialysis therapy (r = 0.35, n = 34, p < 0.04).
      Specificity for cTnI in renal impairment patients was 96% [78-100] and 100% [84
      100] in continuous ambulatory peritoneal dialysis and all hemodialysis patients.
      None of the studied markers showed higher specificity than cTnI. Only myoglobin
      was less specific than cTnT in hemodialysis patients. Different clearances of the
      troponins during dialysis (investigated by pre-hemodialysis and post-hemodialysis
      levels) cannot explain the discordant results of cTnT and cTnI. CONCLUSION:
      Cardiac troponin I exhibits higher specificity than cardiac troponin T in
      hemodialysis patients. Uremic myopathy could explain falsely elevated troponin T
      levels in hemodialysis patients.

PMID- 9594045
TI  - Blood and tissue findings in the diagnosis of mesenteric ischaemia: an
      experimental study.
AB  - In this experimental study, after inducing mesenteric ischaemia in dogs, we
      investigated routine blood biochemistry, serum malondialdehyde (MDA) levels,
      histopathological changes and tissue MDA levels in the liver and intestines. The
      study group included 10 dogs. Six dogs which underwent sham operation served as
      controls. In the study group, the MDA level in liver tissue increased after
      superior mesenteric artery (SMA) ligation. Various degrees of necrosis were seen
      in the ileal biopsies 10 hours after the ligation. Hyperaemia and focal necrosis
      in the liver accompanied the intestinal necrosis if it was limited within the
      mucosa. However, massive or centrilobular necrosis was observed in the liver of
      those dogs which had intestinal necrosis that extended into muscular layers. MDA
      levels in intestinal tissue measured after SMA ligation were significantly higher
      than the preligation levels. On the other hand, the difference between serum and
      tissue MDA levels was not significant. The alterations in MDA were not
      significant in the sham group. Thus it is concluded that the serum MDA levels are
      valuable markers of diagnosis in intestinal ischaemia.

PMID- 9594046
TI  - Fucosylation and galactosylation of IgG heavy chains differ between acute and
      remission phases of juvenile chronic arthritis.
AB  - Oligosaccharide structures are attached to nearly all membrane and serum
      proteins, and their composition changes significantly in many diseases. We have
      analysed glycosylation of IgG heavy chains in 34 patients with juvenile chronic
      arthritis and 13 control individuals. IgG was purified from 0.7 ml of serum,
      separated by electrophoresis and transferred on to polyvinylidene difluoride
      (PVDF) membrane. Ricinus communis agglutinin (RCA I) and Bandeirea simplicifolia
      (BSA II) and Ulex europaeus (UEA I) lectins were used to measure galactose, N
      acetylglucosamine and fucose, respectively. While there was no significant
      difference in average levels of galactose and N-acetylglucosamine, patients with
      juvenile chronic arthritis had 2.4 times more fucose attached to IgG heavy chains
      than control individuals. A different picture emerged when patients were divided
      into those with acute disease and those in remission. Patients in whom juvenile
      chronic arthritis was currently active had significantly lower levels of
      galactose than those in remission, in whom galactose levels were comparable to
      the control group. Fucose levels in both groups of patients were significantly
      higher than in the control group. These results show that whereas de
      galactosylation is a good test to detect and measure the activity of juvenile
      chronic arthritis, increased fucosylation is a much more reliable measure for
      diagnosis of the disease itself.

PMID- 9594047
TI  - Analytical evaluation of an improved procedure for measuring thyrotropin.
AB  - The analytical characteristics of the AxSYM Ultrasensitive hTSH-II (Abbott
      Laboratories) procedure for quantitation of serum thyrotropin (TSH) concentration
      were evaluated. Within- and between-run imprecisions, functional sensitivity,
      analytical interval and relative inaccuracy with respect to the Enzymum-Test TSH
      (Boehringer Mannheim) were studied. In all cases, the within-run and between-run
      of coefficients variation were lower than 6.69% and 8.12% respectively. The
      measurement range was tested with serial dilutions of a serum with a high
      thyrotropin concentration, and the procedure was found to be linear up to at
      least 87.0 mIU/l. The functional sensitivity was 0.018 mIU/l. The relative
      inaccuracy study (Passing-Bablok non-parametric linear regression) produced the
      following linear equation: (AxSYM) = 1.02. (ES-700)-0.03 mIU/l, with 95%
      confidence intervals of a (-0.05; -0.01); b (0.98; 1.06).

PMID- 9594048
TI  - Erroneous monocyte and neutrophil counts with the Sysmex NE-1500 in patients
      recovering from bone marrow aplasia.
AB  - The Sysmex NE-1500 is a haematological analyser which offers five-part
      differential counts. The instrument was submitted to an extensive evaluation
      procedure before acceptance to the laboratory and was found to perform
      satisfactorily. However, problems arose in clinical practice with the analysis of
      samples from patients recovering from bone marrow aplasia. Falsely low monocyte
      counts and, controversely, falsely high neutrophil counts were found in these
      patients. Only a minority (13%) of these samples were flagged as abnormal by the
      instrument. The most alarming consequence of these results is the overestimation
      of neutrophils and the exclusion of these patients from reimbursement for
      treatment with growth factors. We conclude that in patients recovering from
      aplasia, differential counts performed with the Sysmex NE series should always be
      checked manually.

PMID- 9594049
TI  - N-benzoyl, L-glutamic acid as a suitable internal standard for the analysis of
      trans,trans-muconic acid in human urine by liquid chromatography.
AB  - Urinary trans,trans-muconic acid is a sensitive biomarker for low level benzene
      exposure. The method described by Ducos et al. (Int Arch Occup Environ Health
      1990; 62:529-34) is commonly used for its determination. In this study, we
      demonstrate that N-benzoyl, L-glutamic acid added to urine samples is a suitable
      internal standard to control trans,trans-muconic acid recovery after solid phase
      extraction of urine and to compensate for variations which might occur during
      high-performance liquid chromatography analysis.

PMID- 9594050
TI  - Acute exogenous elevation of plasma free fatty acids does not influence the
      plasma magnesium concentration.
AB  - OBJECTIVE: Plasma non-esterified (free) fatty acid concentrations rise as a
      consequence of stimulated endogenous lipolysis and are inversely related to the
      plasma magnesium concentration when plasma adrenaline concentration is increased.
      The aim of the study was to test whether high plasma non-esterified fatty acid
      concentration after infusion of non-esterified fatty acids decreases plasma
      magnesium concentration. METHODS: Twelve healthy subjects received 500 ml
      Intralipid or saline in a randomised, cross-over, double-blind design. Infusion
      of Intralipid results in an isolated elevation of plasma non-esterified fatty
      acid concentration. Plasma magnesium concentration was determined at baseline and
      every 30 minutes; plasma non-esterified fatty acid and triglyceride
      concentrations at baseline and after 120 minutes. RESULTS: Initial plasma
      magnesium, non-esterified fatty acid, and triglyceride concentrations were
      similar in both groups. A significant increase in plasma non-esterified fatty
      acids (2.42 +/- 0.96 mmol/l vs 0.58 +/- 0.23 mmol/l, p = 0.00013) and
      triglyceride (median and 95th percentile 5.36 (7.35) mmol/l vs 1.18 (1.92)
      mmol/l, p = 0.003) concentrations was seen with Intralipid. Plasma magnesium
      concentration increased significantly after Intralipid (0.89 +/- 0.09 mmol/l vs
      0.81 +/- 0.06 mmol/l, p = 0.007). No significant changes were seen with saline. A
      positive association was found between the change in plasma magnesium and
      triglyceride concentrations (r = 0.85, p = 0.001). CONCLUSION: Acute infusion of
      non-esterified fatty acids from an exogenous source does not result in a fall in
      plasma magnesium concentration, indicating that the circulating non-esterified
      fatty acids play no part in a decrease in plasma magnesium concentration. The
      high circulating non-esterified fatty acid levels and the fall in plasma
      magnesium concentration are both a consequence of intracellular lipolysis.

PMID- 9594051
TI  - Characterisation and evaluation of external quality assessment scheme serum.
      Discussion paper from the European External Quality Assessment (EQA) Organisers
      Working Group C.
AB  - This work reviews the procurement, specification and manufacture of serum for
      external quality assessment (EQA) and provides a checklist for scheme organisers.
      Guidance on the assessment of commutability and notes on the use of EQA materials
      to assess assay problems are provided. The importance of the appropriateness of
      materials in respect of scheme design and objectives, and the essential nature of
      a detailed specification prior to manufacture are emphasised.

PMID- 9594052
TI  - Need for correct estimates of biological variation: the example of C-reactive
      protein.

PMID- 9594053
TI  - Health care reform. Implications for dentistry and minorities.

PMID- 9594054
TI  - Report of a case: immediate placement of a root form implant into an extraction
      site.

PMID- 9594055
TI  - Extractions in support of orthodontic treatment.
AB  - Extractions in support of orthodontic therapy may be done in any combination of
      teeth. The more common extraction patterns are: 1. Maxillary and mandibular first
      premolars; 2. Maxillary first and mandibular second premolars; 3. Maxillary and
      mandibular second premolars; 4. Maxillary first premolar; 5. Maxillary second
      permanent molar; 6. Maxillary first permanent molars; 7. Maxillary permanent
      lateral incisors; 8. Mandibular permanent incisors; or 9. Any possible
      combination and variation for other considerations. Extractions have been proven
      to support changes in the profile, helping in the alignment of teeth and in
      reducing lower facial height. The decision as to whether or not to extract
      requires a great deal of thoughtful application of diagnostic skills.

PMID- 9594056
TI  - A radiographic survey of dental anomalies in Black pediatric patients.
AB  - During seemingly routine check-ups, the dental practitioner must be ever aware of
      "quiescent" abnormalities or irregularities. Knowledge of special problems
      occurring within a certain patient population is of great value to the
      practitioner when evaluating the individual patient. Numerous studies have been
      conducted evaluating the pediatric Caucasian population; however, no comparable
      studies for the Black pediatric population have been done. This study sought to
      establish prevalence rates for the Black pediatric population with regards to the
      following anomalies: congenitally missing teeth, supernumerary teeth, dens in
      dente, odontomas, dentinogenesis imperfecta, gemination, fusion and concrescence.
      The radiographs (panographs mandatory), history forms and treatment progress
      records of 2,267 children (1,136 males and 1,131 females) were analyzed.
      Radiographs of poor quality were eliminated and attempts were made to include
      only children of Black American heritage. Prevalence rates established for a
      predominantly Black pediatric population were: 4.4%, congenitally missing teeth;
      1.49%, supernumerary teeth; 0.26%, dentinogenesis imperfecta (Brandywine type);
      0.44%, odontomas; 0.22%, gemination; and 0.12%, fusion. Evidence of dens in dente
      was found in only one erupted supernumerary maxillary paralateral, and the
      detection of only one case of concrescence occurred; both have prevalence rates
      of 0.04%. No other study has produced such a high rate of dentinogenesis
      imperfecta (.26%), except that conducted within the tri-racial group itself. In
      addition, if assumptions are to be made from this investigation for the general
      population, supernumeraries and odontomas may be present significantly more often
      in the Black than Caucasian pediatric population.

PMID- 9594057
TI  - The effect of non-surgical management of TM disorders.
AB  - One hundred and ninety-three patients with varying occlusal discrepancies were
      diagnosed as having TM disorders with orofacial pain. They were divided into five
      groups with similar clinical symptomatology. There were 84 patients with
      clicking, 45 with headaches, 13 with neckaches, 39 with tenderness in the TMJ
      bilaterally and masticatory muscles and 12 with uncomfortable occlusal
      relationships. All were given an anterior deprogrammer to wear for a period of
      one week in order to relax the masticatory muscles and allow the jaw to return to
      a physiologic position. The follow-up occlusal device therapy varied according to
      clinical symptoms. The group with clicking wore anterior repositioning orthopedic
      devices to recapture the displaced articular disc, followed by a gradual return
      to a centric relation position. The other groups wore centric relation appliances
      providing even posterior cusp tip contacts and anterior guidance. All patients
      wore the appliances for varying periods, up to one year, with monthly
      adjustments. The clinical symptoms significantly decreased, and all but 4
      patients who had to be treated surgically, had the malocclusion corrected at the
      same treatment position of the centric relation appliances that were worn for one
      year. The results suggest that short-term occlusal device therapy is effective as
      an interim method towards the correction of occlusal discrepancies, but should be
      followed by a final treatment that will maintain the jaw in an asymptomatic and
      physiologic position. Four-year re-evaluations revealed no reoccurrence of
      chronic symptoms after finalization treatment.

PMID- 9594058
TI  - Halo nevus: an unusual upper lip presentation in a black patient and a review of
      the subject.

PMID- 9594059
TI  - The dental health care system and minority patients.

PMID- 9594060
TI  - The CO2 laser as an adjunctive therapy in a general practice.

PMID- 9594061
TI  - Dental managed care: an opportunity for empowerment.

PMID- 9594062
TI  - The effects of temperature on the strength of composites.

PMID- 9594063
TI  - Histologic study of pulp capping using chlorhexidine in dogs.
AB  - This histological study was conducted to compare the pulp reactions to
      chlorhexidine and calcium hydroxide. Twenty permanent premolar teeth of beagle
      dogs were mechanically exposed under aseptic conditions. The pulp was then capped
      with one of the following: chlorhexidine 0.2% on the left side and calcium
      hydroxide (dycal) on the right side of the same dog. Maxillary second premolars
      were extracted from each dog three weeks after the pulp capping procedure.
      Maxillary third premolars and mandibular first premolars were extracted at 6
      weeks and 9 weeks respectively. The mandibular second premolars were extracted
      three months after the pulp capping procedure. The specimens were fixed in 10%
      formalin and decalcified in 5% formic acid. Serial sections, 7 microns thick,
      were prepared and stained with hematoxylin and eosin. Teeth treated with
      chlorhexidine or with calcium hydroxide were well tolerated by the dental pulp at
      3 and 6-week intervals. Pulps treated showed satisfactory pulp reaction and the
      odontoblastic layer appeared to be normal and in its configuration. Inflammatory
      response was not present at the 6-week time interval. At nine weeks, the
      inflammatory response was severe in those teeth treated with calcium hydroxide.
      There were no remarkable histological differences among the treatment groups at
      12 and 15 weeks. These specimens showed complete loss of pulpal architecture.
      Regressive changes were seen and microscopic specimens revealed presence of
      spaces and intertwining bundles of films in the pulp.

PMID- 9594064
TI  - Comparative epidemiology of dental caries for black first-graders in Oakland, CA.

PMID- 9594065
TI  - A new advance in sports dentistry.

PMID- 9594067
TI  - Dentistry for the 21st century: laser technology.
AB  - Lasers hve been used experimentally for nearly 40 years. Most applications in
      dentistry maintain use in oral and periodontal pathology. The use of lasers as an
      adjunct therapy in a general dental practice has recently been considered within
      the last 5 years. This article will consist of a literature review of the most
      recent applications in a clinical dental practice.

PMID- 9594066
TI  - Salivary count of Streptococcus mutans in elementary school children.
AB  - Previous studies have documented that persons with high levels of Streptococcus
      mutans are "at risk" for dental caries. The objective of this study was to
      identify children at an early age who were "at risk" for caries. The sample
      consisted of 77 school children aged 9-13 years old. The majority of the sample
      was African-Americans (55.8%). Approximately 51% were females. The Dentocult SM
      Strip Mutans Test was used to estimate the S. mutans count in saliva. The method
      is based on the use of a selected culture broth and the adhere S. mutans count of
      < 1,000,000 bacteria ml saliva and children with S. mutans count of < 1,000,000
      were classified as "low risk" for caries. The DMF-T was used to estimate the
      number of decayed, missing and filled teeth. The decayed mean score = 1.85; range
      = 0-9. Only two children had teeth missing (one in each). The number of filled
      teeth was low; mean = .88; range = 0-6. The DMF-T mean score was 2.75; range = 0
      9. Correlations were sought between levels of S. mutans rates and decayed teeth.
      Low, but nonsignificant, correlations were found between S. mutans and decayed
      teeth (r = .20). This trend continued for S. mutans levels and the DMF-T (r =
      .16). Analysis of Variance Test (ANOVA) indicated a significant effect by sex on
      the levels of S. mutans P < .05 (females had higher S. mutans levels than males).
      There was no significant difference or interaction noted in DMF-T scores by sex
      or race. In addition no significant difference was noted in the number of decayed
      teeth by sex or race. Our results indicate that females in this age group are
      potentially at greater risk for dental caries than their male counterparts due to
      the observed higher levels of S. mutans. This observation deserves further study.

PMID- 9594068
TI  - Analysis of the insertion characteristics of Tn4351 during high frequency
      transposition of Porphyromonas gingivalis.
AB  - In this study, we characterized the high frequency transfer of the Bacteroides
      fragilis transposon Tn4351 into the chromosome of Porphyromonas gingivalis using
      a system developed by Genco, et al. Using this system, transconjugants were
      isolated and genomic sequences analyzed using both Ava-I and EcoR1 to determine
      the insertion characteristics of Tn4351 into the genome of P. gingivalis.
      Although previous evidence pointed to the possibility of random insertion, this
      study shows that, in fact, the insertion characteristics of Tn4351 into the
      genome of P. gingivalis are nonrandom and predictable.

PMID- 9594069
TI  - Comparison of thermoplasticized gutta-percha root canal obturation technique to
      the lateral condensation.
AB  - This in vitro study compared the quality of filling the root canal by the
      conventional lateral condensation technique to the fill by the commercially
      available thermoplasticized gutta-percha method. Subjective radiographic
      evaluation of density, presence of voids, and extent of fill were made for each
      of the 20 freshly extracted maxillary central incisors used for this study. Voids
      were noted in 10% of the laterally condensed canals, versus 40% of those
      obturated with the thermoplasticized gutta-percha. The mean time (in seconds) to
      obturate the canals with lateral condensation was 387 (s = 112); of the
      experimental was 145 (s = 23). We conclude that thermoplastisizing and injecting
      the gutta-percha into the root canal was a fast and a relatively easy technique,
      but the resultant filling was no more dense, and was shorter apically than the
      laterally condensed gutta-percha.

PMID- 9594070
TI  - Arch expansion with Kloehn headgear.

PMID- 9594071
TI  - Longitudinal cephalometric appraisal of maxillary protrusion in African
      Americans: a comparison with European Americans.

PMID- 9594073
TI  - Carpal tunnel syndrome: a dental hygienist's fate? Facts you should know and
      practice.

PMID- 9594072
TI  - The professional socialization of dental hygienists: from dental auxiliary to
      professional colleague.
AB  - Dental hygiene, as an emerging profession, has identified key attributes and
      attitudes of the professional socialization process that are necessary to a
      continued growth and ability of its members to serve the needs of the public.
      Restraints to the professionalization process have been identified as impeding
      both the growth of dental hygienists and confining the delivery of dental hygiene
      services to traditional and supervised settings. Research has demonstrated the
      educational preparation of both the baccalaureate and associate/certificate
      degree dental hygienist can provide the opportunity for professional
      socialization whereby the care provider attains those attitudes deemed necessary
      to practice in a professional mode. Studies have also indicated that dental
      hygienists favor full professional status for dental hygiene through support for
      self-regulation and autonomy. In the light of health care reform, full
      utilization of all members of the health care team will be the most prudent use
      of health care funds. As dental hygiene emerges as a profession, registered
      hygienists will need to identify and define the conceptual framework for the oral
      hygiene practice of the future.

PMID- 9594074
TI  - A dental hygiene perspective in the detection of diabetes mellitus.
AB  - The number of Americans with diabetes mellitus has increased 50% since 1983 to 16
      million. An interesting and startling factor is that only half of these diabetics
      are aware they have the disease. Diabetes mellitus can lead to blindness, heart
      disease, stroke, nerve damage, kidney failure, and periodontal disease. It is the
      fourth leading cause of death in the United States. A metabolic disorder
      affecting insulin metabolism and associated blood glucose intolerance regulation,
      diabetes may be classified by the following categories: type I-insulin dependent
      diabetes mellitus which is commonly found in children and adolescents and type II
      non-insulin-dependent or adult-onset diabetes which occurs in patients over forty
      and is associated with obesity. The dental hygienist's role in education,
      prevention, and therapeutics has expanded to detection and recognition of oral
      manifestations of diabetes. The dental hygienist may be the first to recognize
      the presence of the disease. This article aims to acquaint the dental hygienist
      with the clinical picture of a dental patient with diabetes mellitus.

PMID- 9594075
TI  - Tobacco use among youths.

PMID- 9594076
TI  - The miswak chewing stick: a traditional oral hygiene aid.
AB  - The miswak chewing stick is an oral hygiene device used by the majority of people
      in Arab Gulf countries. Despite its widespread use, few studies demonstrated its
      benefits or applications as an alternative and convenient means for cleansing the
      teeth. This paper will examine the unique properties of the miswak chewing stick
      and its proper use.

PMID- 9594077
TI  - Microleakage evaluation of two newly introduced hybrid glass ionomer cements.
AB  - This study evaluated the microleakage of Photac-Fil Aplicap (ESPE) and Fuji II LC
      (GC) glass ionomer cements. Polished Class V restorations were compared with non
      polished restorations. No measurable microleakage was detected after
      thermocycling and staining in India ink dye. Polishing the restorations had no
      effect on the degree of microleakage.

PMID- 9594078
TI  - Case record analysis: biopsied lesions in a high-risk white and African American
      Community.
AB  - OBJECTIVES: The purpose of this secondary data analysis was to characterize
      biopsied intraoral lesions documented from neighborhood health center records in
      a lower socioeconomic biracial community over an eight year period, (1982-1989.)
      METHODS: A thorough intraoral examination, which included radiographs, was
      completed by either a general dentist or an oral surgeon. Questionable lesions
      were referred to and biopsied in the Department of Pathology at Johns Hopkins
      Medical Center. Biopsied lesions were classified into three groups for analysis:
      benign, malignant/premalignant, and dental-related. RESULTS: Of 13,317 recorded
      dental visits, 10,819 (81.2%) visits were made by African Americans. There were
      341 lesions biopsied, representing 69 different histologic diagnoses. Of
      identified lesions, 76.5% were in African Americans; 41.6% were in males, ranging
      in age from 41 to 94 years old (a mean age of 73 +/- 7 years). Approximately 50%
      of identified lesions in African American and Whites were benign. Among African
      Americans, 11.9% of the lesions were malignant premalignant, while 16.3% were
      among Whites. Within the malignant/premalignant category, squamous cell carcinoma
      was the most frequently identified malignant lesion. Hyperkeratosis was the most
      common premalignant lesion type. CONCLUSIONS: Neighborhood health centers can
      provide a valuable screening service identifying intraoral lesions in vulnerable
      communities. Future research should explore how socioeconomic factors affect
      differences in the prevalence of intraoral pathologies among White and African
      American subgroups as well as other subpopulations.

PMID- 9594079
TI  - Predictive medicine.

PMID- 9594080
TI  - Standardization and clinical management of lipoprotein(a) measurements.
AB  - The present article proposes personal suggestions to improve determinations and
      clinical interpretation of results of lipoprotein(a) assays. Methods and
      procedures for sampling and quantification of the various isoforms of
      lipoprotein(a) in serum, plasma and urine are reviewed with the aim of improving
      the reliability and reproducibility of results and reinforcing the clinical
      utility of lipoprotein(a) measurements.

PMID- 9594081
TI  - Evaluation of the iron status of the newborn by soluble transferrin receptors in
      serum.
AB  - The concentration of soluble transferrin receptors in serum has proven to be a
      reliable predictor of iron status in adults. Its high sensitivity for iron
      deficiency combined with a small sample size (10 microliters) makes it an
      interesting parameter for the assessment of iron stores in newborn infants. In
      the present study we investigated the usefulness of the concentration of soluble
      transferrin receptors in serum in the assessment of iron metabolism in the
      newborn. Infants born after an uncomplicated labour were compared to infants in
      the intensive care unit. The concentration of soluble transferrin receptors in
      serum was found to be elevated compared to normal adults and independently of
      iron metabolism. The concentration of soluble transferrin receptors did not
      correlate with serum iron and ferritin concentrations. In contrast to what was
      found in other studies, no relationship could be demonstrated between soluble
      transferrin receptors and birth weight or gestational age. The results of this
      study have shown that care has to be taken in the interpretation of the
      concentration of soluble transferrin receptors in serum in newborn infants. It
      seems to be a parameter which is independent of iron metabolism at least during
      the first days of life.

PMID- 9594082
TI  - Quantitation of IgG and IgM human anti-mouse antibodies (HAMA) interference in CA
      125 measurements using affinity chromatography.
AB  - Currently no available immunoassay system offers complete protection against
      spuriously elevated or lowered results due to interference by Human Anti-Mouse
      Antibodies (HAMA). Although routine use of chromatography procedures is not an
      acceptable option because of the extra cost and workload involved, such a
      procedure would be highly desirable to ensure accurate immunoassay results. The
      present report describes a relatively simple affinity chromatography procedure
      using a HiTrap Protein G column to isolate immunoglobulin G (IgG) HAMA, followed
      by a HiTrap N-hydroxy-succinimide (NHS)-activated column coupled to goat-anti
      human immunoglobulin M (IgM) to bind IgM HAMA. To examine the usefulness of this
      purification procedure we determined CA 125 in forty serum samples prior to and
      following chromatography. Pre- and post-injection samples were obtained from 20
      patients injected with 1 mg of 111In-labelled murine OC 125 F(ab')2 fragments in
      an immunoscintigraphy study. It is shown that this analytical procedure provides
      a technique to determine the extent and the nature of the existing HAMA
      interference in samples of patients after in vivo use of monoclonal antibodies
      for diagnostic or therapeutic purposes. The procedure can also contribute to the
      clarification of clinically discordant CA 125 results. Finally, the availability
      of such a procedure in the clinical laboratory provides an opportunity to test
      the robustness of newly developed immunoassay systems towards HAMA interference.

PMID- 9594083
TI  - Neopterin plasma concentrations predict the course of severe acute pancreatitis.
AB  - In a prospective, descriptive study in 25 patients with acute pancreatitis
      neopterin plasma concentrations were found to be associated with the severity of
      the disease, which was assessed using weights of the worst 17 physiological
      abnormalities of the APACHE-III score over a 24 h-period after hospital
      admission. Neopterin concentrations were higher in severe pancreatitis (n = 10)
      compared to mild disease, and there existed a positive exponential correlation
      between neopterin and the Acute Physiology Score (r = 0.66). Higher neopterin
      concentrations were associated with the development of multiple organ failure (p
      = 0.012) and death (p = 0.019). At a cut-off concentration of 12 nmol/l the
      sensitivity (80%) and specificity (100%) of neopterin for the discrimination
      between mild and severe clinical course of pancreatitis was more accurate than C
      reactive protein at a risk threshold of 1.2 g/l (70% and 87%). Development of
      pancreatic necrosis was associated with higher neopterin concentrations than
      edematous pancreatitis (p < 0.001).

PMID- 9594084
TI  - Objectives, design and recruitment of a familial and longitudinal cohort for
      studying gene-environment interactions in the field of cardiovascular risk: the
      Stanislas cohort.
AB  - The main objective of the Stanislas cohort is to study the role and the
      contribution of genetic and environmental factors to cardiovascular status. We
      plan: a) to describe the degree of association of a large number of
      cardiovascular risk indicators with cardiovascular endpoints, b) to evaluate the
      contribution of genetic and that of environmental factors to this association, c)
      to follow the evolution of these risk indicators during a period of at least ten
      years, d) to search for the determinants influencing this evolution. The
      principal variables studied are: a) blood pressure, cardiac mass, and wall
      thickness of carotid and femoral arteries, b) obesity and fat mass, c) indicators
      of lipid metabolism, d) genetic polymorphisms of several cardiovascular risk
      candidate genes, e) food, tobacco and alcohol consumption, f) consumption of
      drugs and anti-oxidant vitamins. Between September 1993 and August 1995, 1006
      families consisting of the two biological parents with at least two children were
      recruited totalling 4295 individuals. This cohort will be followed up until 2004.
      There will be two health examinations five and ten years after the initial
      examination. A bank of blood samples (serum and plasma) in liquid nitrogen and
      DNA (-80 degrees C) has been established.

PMID- 9594085
TI  - Total carbon dioxide measured by the Vitros enzymatic method.
AB  - We evaluated the performance of an enzymatic method using dry chemistry for serum
      total carbon dioxide (tCO2) determination using a Vitros 500 analyser.
      Imprecision results were acceptable and the linearity was verified for
      concentrations within a range of 5.5-39.2 mmol/l, i.e. Y(measured) = 0.93
      x(calculated) + 1.32, r = 0.99. The Vitros tCO2 method was unaffected by
      haemoglobin at all concentrations tested. Significant interference was caused by
      bilirubin at concentrations higher than 30 mumol/l; the addition of bilirubin
      lowered the apparent values for tCO2 dose-dependently. Serum tCO2 results were
      practically the same as those for plasma. The reference interval for venous tCO2
      concentrations in a healthy population was: 22.4-34.2 mmol/l (mean: 28.3 mmol/l).
      Comparison of venous serum tCO2 results assayed using the Vitros method with
      bicarbonate (HCO3-) values calculated by blood gas determination of pCO2 and pH
      in arterial blood samples gave poor agreement, r = 0.58. The data revealed a mean
      difference of 5.48 +/- 3.09 mmol/l between the tCO2 measurements and calculated
      bicarbonate. This was statistically (p = 0.01) and clinically significant. We
      conclude that the Vitros method provides reliable tCO2 results in venous serum
      but this method must not be used as an interchangeable alternative to calculated
      arterial bicarbonate in order to avoid confusion, misinterpretation of results
      and erroneous therapeutic decisions.

PMID- 9594086
TI  - Evaluation of Glucocard Memory 2 and Accutrend sensor blood glucose meters.
AB  - The performance and practicability of 2 blood glucose meters (Glucocard Memory 2
      and Accutrend sensor) were evaluated. Both glucose meters produced acceptably
      precise results in the hyper- and normoglycaemic concentration ranges. In the
      hypoglycaemic concentration range, the imprecision of Accutrend sensor was much
      higher than recommended by the American Diabetes Association. Within-run
      coefficients of variation for Glucocard Memory 2 were 6.3%, 3.9% and 2.4% at
      glucose concentrations of 1.7 mmol/l, 5.8 mmol/l and 11.7 mmol/l, respectively:
      for Accutrend sensor these were 15.2%, 5.0% and 1.2% at respective concentrations
      of 0.9 mmol/l, 4.2 mmol/l and 19.6 mmol/l. Between-day coefficients of variation
      for Glucocard Memory 2 were 4.8% and 3.5% at glucose concentrations of 3.9 mmol/l
      and 17.2 mmol/l, respectively and for Accutrend sensor they were 3.8% and 2.9% at
      glucose concentrations of 3.8 mmol/l and 18.7 mmol/l, respectively. Results were
      linear over a range of 1.6 mmol/l -29.7 mmol/l for Glucocard Memory 2 and 1.6
      mmol/l -33.3 mmol/l for Accutrend sensor. Results of both blood glucose meters
      correlated closely with the hexokinase/glucose-6-phosphate dehydrogenase
      laboratory method. Ninety-eight percent of both Glucocard Memory 2 and Accutrend
      sensor results were within 20% of the comparison method values. Ninety-three
      percent of the Glucocard Memory 2 and 96% of the Accutrend sensor results were
      within 15% of the comparison method results. An inverse relation between the
      glucose readings and haematocrit values was observed for both blood glucose
      meters in the hyperglycaemic range and this effect was more pronounced for
      Accutrend sensor. In the normo- and hypoglycaemic ranges the effect was
      insignificant and absent, respectively. Minimum sample volume for Glucocard
      Memory 2 was 3 microliters and for Accutrend sensor it was 9 microliters. Lower
      sample volumes gave erroneous results. Presenting more than the required volume
      had no effect on results.

PMID- 9594087
TI  - Evaluation of circulating type I procollagen propeptides in patients with Paget's
      disease of bone.
AB  - We evaluated circulating aminoterminal and carboxyterminal propeptides of type I
      procollagen and total alkaline phosphatase levels in eighty consecutive patients
      affected by Paget's disease of bone. We compared the biochemical data with the
      extent of bone disease calculated on the basis of the bone scintigraphic indices.
      Serum aminoterminal propeptide of type I procollagen levels were high in 77% of
      patients, serum carboxyterminal propeptide of type I procollagen levels in 22%
      and serum total alkaline phosphatase levels in 76%. We found significant
      correlations between the three markers studied. The three biochemical markers
      correlated significantly with the bone scintigraphic activity indices, but the
      highest correlation coefficient was between the aminoterminal propeptide and
      total alkaline phosphatase. We conclude that there is a discrepancy between serum
      levels of the propeptides studied in relation to Paget's disease of bone. The
      sensitivity of the carboxyterminal propeptide of type I procollagen in this
      disease is low. In contrast the aminoterminal propeptide may be as sensitive a
      marker for the evaluation of this disorder as total alkaline phosphatase, and in
      addition may be more specific.

PMID- 9594088
TI  - Properties and units in the clinical laboratory sciences. XIII. Properties and
      units in reproduction and fertility. International Society of Andrology (ISA).
      International Union of Pure and Applied Chemistry. International Federation of
      Clinical Chemistry and Laboratory Medicine.

PMID- 9594089
TI  - Procalcitonin as a specific marker of bacterial infection in adults.

PMID- 9594090
TI  - Biological variation and quantification of health: the emergence of the concept
      of normality.
AB  - Historical research on the concept of normality, its roots and its development
      show that this concept has its sources in very different areas of scientific and
      medical thinking. Of great importance were: (i) a new theory of disease arising
      early in the 19th century supposing a continuous change from the healthy to the
      diseased state; (ii) the examination of variation within and between species of
      plants and animals; (iii) the clinical theory of constitution developed to
      describe the wholeness of the individual determined both by genetic factors and
      the influence of the environment; (iv) the development of mathematical and
      statistical tools starting with the adaptation of Bernoulli's "law of the great
      numbers" and Gauss' and Legendre's "law of errors" to biological measurements by
      the Belgian astronomer Quetelet. At the end of the First World War the concept of
      normality was first discussed. An idealistic "value norm" was set against a
      statistical "frequency norm". Between 1920 and 1930 the principles of our present
      concept were accepted and the mathematical tools developed. It took several
      decades to introduce this concept into practical medicine finally being
      recommended by the IFCC.

PMID- 9594091
TI  - Critical thinking. Painting health care red.

PMID- 9594092
TI  - Sometimes it seems that the only thing constant in today's society is change.

PMID- 9594093
TI  - Current perspectives in oxygenation and ventilation--Part II.
AB  - This is the second part of the discussion on current perspectives in oxygenation
      and ventilation. The focus is on modes of ventilation. Intended goals of
      ventilation therapy are discussed, particularly in relation to work of breathing
      and oxygen delivery. Current modes of ventilation are reviewed, with advantages
      and disadvantages of the types of therapy presented in summary tables.
      Consideration is given to the broader perspective of ventilation therapy, that
      is, improving the balance between oxygen delivery and tissue oxygen needs.
      Optimizing the oxygen balance includes nursing interventions directed toward
      decreasing oxygen demands.

PMID- 9594094
TI  - An innovative approach to pain management in critical care: therapeutic touch.
AB  - Nursing research suggests that pain in critically ill patients is inadequately
      controlled and has deleterious effects. The critical care nurse must depend on
      the patient's perception of pain and its expression in physiological and
      behavioural responses. Ventilatory support, fluctuating levels of consciousness,
      hemodynamic instability and severity of illness are often barriers to the
      expression and interpretation of pain. This article includes a review of the
      nursing literature pertaining to pain management in the critically ill patient.
      Existing practices are examined and alternative approaches explored. Therapeutic
      touch (TT), one innovative approach, is proposed as an adjunct to pharmacological
      intervention TT is a non-invasive, holistic practice that promotes comfort,
      relaxation, stress reduction and heating. Clinical studies suggest that TT
      prolongs the interval between analgesies. The authors highlight the 10-year
      clinical experience of a critical care nurse practising TT in a 30-bed critical
      care and trauma centre.

PMID- 9594096
TI  - Thoughts on leadership.

PMID- 9594095
TI  - The use of limited critical care resources: an ethical dilemma.
AB  - The following article consists of a review of the literature surrounding the
      issue of persistent vegetative state (PVS) patients and resource allocation. The
      author attempts to analyze the question: Should limited critical care resources
      be used on PVS patients at the risk of denying those resources to others? The
      author explores such factors as: prognosis and recovery in PVS, life expectancy,
      and quality of life. As well, resource availability and ICU costs involved in
      sustaining the life of a PVS patient are examined. Finally, principles such as
      non-maleficence and beneficence; as well as the critical care professionals
      attitudes toward this issue; and the moral, ethical, and emotional dilemmas are
      discussed.

PMID- 9594097
TI  - A survey of current ventilator circuit changes in intensive care units in
      England.
AB  - A survey of intensive care units (England) aimed at identifying current practices
      in ventilator circuit changes. A random sample of 180 units were surveyed, 152
      (84%) questionnaires were returned. The results demonstrated a wide range of
      current practices regarding circuitry and related respiratory equipment changes.
      Tentative recommendations for practice are suggested based on current knowledge
      and evidence from previous studies.

PMID- 9594098
TI  - Counselling and support in intensive care.
AB  - Counselling and support can improve psychological care and help patients and
      relatives through the emotional distress of critical illness. This paper
      considers the dual role of nurse and counsellor. Experience of developing a
      counselling and support service are shared. Choosing a theory and the counselling
      process is considered.

PMID- 9594099
TI  - Preventing post traumatic stress disorder in accident and emergency nursing. A
      review of the literature.
AB  - Nurses working in Accident and Emergency may be susceptible to post-traumatic
      stress disorder (Rentoul and Ravenscroft 1993, Scott and Stradling 1994). The
      literature suggests that defusing immediately following a resuscitation may help
      to reduce abnormal stress reactions (Mitchell, 1988; Wright, 1992, 1993).
      Critical incident stress debriefing is recommended following critical incidents
      to help prevent emergency personnel developing post-traumatic stress disorder
      (Jimmerson, 1988; Mitchell, 1983, 1988; Parkinson, 1995).

PMID- 9594100
TI  - Exploring the nature of informed consent in coronary care practice.
AB  - The nature of informed consent is bound within legal and moral duties. An
      analysis of informed consent includes the elements of understanding, disclosure,
      competence, voluntariness and authorisation, all of which can be affected by a
      variety of factors. Nurses can make a unique contribution to informed consent
      situations either as advocates, interpreters, coordinators, witnesses or culture
      brokers. In order to fulfill their obligations to the patient and manage
      potential conflicts, nurses need to have a substantial awareness to the diversity
      of issues and pitfalls. Communication skills and building a therapeutic alliance
      with the patient are at the heart of nursing care. Nurses are taking on duties
      previously associated with medical practice-it is unclear how this affects their
      roles as information givers.

PMID- 9594101
TI  - Changing practice to primary nursing.
AB  - Primary nursing is now seen as popular method of delivering nursing care. The
      process of introducing this system requires prior planning, involving all members
      of nursing staff. A change in philosophy, culture and roles occurs with the
      introduction of primary nursing. Evaluation of this change is necessary, to
      determine if it is beneficial both to patients and the multidisciplinary team.

PMID- 9594102
TI  - Death: a concept analysis and application to practice.
AB  - Death is a commonly used concept but is surrounded by much mystery. The concept
      of death is examined using the Walker and Avant (1995) framework for concept
      analysis. The use of the concept death is considered in the intensive care unit.
      In the intensive care unit a conflict often exists between the curing culture and
      the inevitability of death.

PMID- 9594103
TI  - Critical care nursing: servants or masters to the universities?

PMID- 9594104
TI  - The role of the clinical nurse specialist in acute pain management.
AB  - A snapshot of the rapidly growing area of the clinical nurse specialist in pain
      management is provided. The conceptual framework for the study was developed from
      Donabedian's (1966) and Hamric's (1989) models The literature review indicated a
      knowledge deficit in the area of patient and cost-benefit evaluation; however,
      the conceptual framework indicated the need to establish the structure and
      process of this new area of practice prior to undertaking an outcome evaluation
      analysis. The study adopted a non experimental, descriptive, cross sectional
      survey design. The majority of the multidisciplinary acute pain services are co
      ordinated by one full time G grade nurse, without any formal training who meets
      all the role dimensions of the clinical nurse specialist, and the role dimensions
      as described by the commission for the provision of Surgical Services (1990).

PMID- 9594105
TI  - Sedation scoring. Assessment tools.
AB  - The changing use of sedative agents, is reviewed. Tools to guide sedation
      assessment are identified, although only one appears to assess level, quality and
      depth of sedation. Several issues concerning reliability and validity of sedation
      assessment tools are discussed. Recommendations for practice are made, which
      highlight the criteria that sedation assessment tools need to address and the
      research directions needed for future tool development.

PMID- 9594106
TI  - A woman's death in the coronary care unit.
AB  - Driscoll's model of reflection is used to review the care of a patient in a
      coronary care unit. Feelings of guilt and frustration were experienced when the
      potential for a peaceful death was nearly lost by a doctor's attempt to make one
      final effort at defibrillation. Implications for nurses' education and support
      are identified within the context of the multidisciplinary team.

PMID- 9594107
TI  - A phenomenological study of ethical decision-making experiences among senior
      intensive care nurses and doctors concerning withdrawal of treatment.
AB  - The study compared and contrasted the experiences of senior doctors and nurses
      ethical decision making concerning the withdrawal of treatment. Doctors generally
      took the primary role in ethical decision making, leaving nurses acting as
      information brokers. Nurses suffered moral distress as a result of the decision
      to withdraw treatment, whilst doctors suffered moral dissonance. Doctors and
      nurses needed to come to terms with withdrawal of treatment. A model of
      communication which will enhance collaborative, multidisciplinary ethical
      decision making is suggested.

PMID- 9594108
TI  - Do nurses perceive that there is a need for defusing and debriefing following the
      resuscitation of a patient in the accident and emergency department?
AB  - Defusing and debriefing are techniques that have been used to prevent staff
      developing psychological problems such as post traumatic stress disorder
      (Mitchell, 1988). It has been identified that nurses may be susceptible to a form
      of post-traumatic stress disorder known as prolonged duration stress disorder
      (Scott and Stradling, 1994). This study employs a non-experimental survey to
      identify the current practice of defusing and debriefing in an accident and
      emergency department and explores nurses' perceptions of the need for defusing
      and debriefing following the resuscitation of a patient. A theoretical framework
      of cognitive therapy is utilised to structure the study.

PMID- 9594109
TI  - Modern critical care unit design. Nursing implications in modern critical care
      unit design: bed area ergonomics.
AB  - Management of the bed area in the critical care unit is important in terms of
      patient management and occupational safety of healthcare staff. There are many
      fundamental considerations concerning the design, layout and aesthetics of the
      bed area. The aesthetics should be an amalgamation of the expectations of
      patients, relatives and healthcare staff. Most of the activity is centered in the
      patient care area, and facilities should be designed according to ergonomic
      considerations.

PMID- 9594110
TI  - Designing and developing a new high dependency unit. Here's one I prepared
      earlier....
AB  - A new high dependency unit is established for postoperative cardiac patients,
      from design to implementation Facilities were incorporated within financial, time
      and space constraints. Layout and use of space was determined for optimal working
      conditions and care of the patient. The choice of equipment was a vital part of
      the high dependency unit. The crucial role of nurses in this project is
      emphasised.

PMID- 9594111
TI  - Dose due to man-made radionuclides in terrestrial wild foods near Sellafield.
AB  - Radiological dose implications for consumers of wild foods around Sellafield have
      been assessed. Habits were surveyed from 72 households, mostly within a few
      kilometres of Sellafield. A few people were included who lived further away but
      collect wild foods close to Sellafield. Dose estimates were based on measured
      gamma emitters, as well as 239Pu, 241Am, 14C and 129I in selected samples. In all
      cases, doses were dominated by 137Cs. One infant was identified who consumed wild
      food, giving an estimated effective dose of 0.3 microSv a(-1). In the age group 2
      to 10 years a mean dose of 0.51 microSv a(-1), and a maximum of 2.8 microSv a(
      1), were estimated. Intakes by adults were higher and resulted in more
      radiologically significant doses. The extreme individual received a dose of 32
      microSv a(-1) largely due to consumption of honey that included contributions
      from the Chernobyl accident, and hedgerow fruits. This is comparable to doses to
      the critical group for consumption of conventional agricultural produce close to
      the Sellafield site. The 97.5th percentile dose, for all age groups of consumers
      taken together, was 16.6 microSv a(-1), or 6.2 microSv a(-1) if the contributions
      from Chernobyl are excluded. Considering the contributions from different foods
      to the whole group of 181 wild food consumers, the rank order is honey,
      blackberries and venison.

PMID- 9594112
TI  - Measurement of krypton-85 in air at Clonskeagh, Dublin 1993-1997.
AB  - The existence of 85Kr in the air is primarily due to the reprocessing of nuclear
      fuel. The two major reprocessing plants in the western world are at La Hague in
      France and Sellafield in the UK. Prior to the commissioning of THORP at
      Sellafield in 1994, a programme to monitor the concentration of 85Kr in air at
      Clonskeagh, Dublin was commenced. While results for the measurements over the
      period 1993-1997 indicate that the concentration of 85Kr in the air is
      increasing, it has not been possible to link any particular measurement result to
      a krypton release from the Sellafield site. The concentration of 85Kr in air, at
      the existing level, does not present a significant radiological hazard. Exposure
      to 85Kr, which is an inert gas, results mainly in small doses to the skin. A mean
      annual concentration of 1.34 Bq m(-3) was calculated for 1997 which would result
      in a skin dose of 0.55 microSv for the year to the exposed skin of an individual.

PMID- 9594113
TI  - Cancer mortality in the commune of Pargny sur Saulx in France.
AB  - Radioactive thorium wastes were found in April 1997 at the former industrial site
      of 'Orflam-Plast' in the commune of Pargny sur Saulx in the Northeast of France,
      where industrial activity began in 1934. On this site, between 1934 and 1970,
      cerium for lighter stones and thorium nitrate were extracted from imported
      monazite sand, a mineral containing elevated levels of natural radioactivity. We
      decided to study cancer mortality in the surrounding population. We found an
      excess of mortality due to lung and bladder cancer in the commune of Pargny sur
      Saulx and its neighbours, between 1968 and 1994. This excess did not seem to be
      linked to the river of Saulx which was a possible source of contamination. We
      conclude that a cancer incidence study of the former workers of this industrial
      site is necessary in order to investigate the role of natural radioactivity from
      monazite processing in the risk of cancer mortality among this workforce.

PMID- 9594114
TI  - Comparative health risk assessment of nuclear power and coal power in China.
AB  - The public health risk of ionising radiation released from the coal-fired energy
      chain, 20 deaths (GW a)(-1), is about 18 times that of the nuclear energy chain,
      1.1 deaths (GW a)(-1), in China. The main contributors to the fatality risk for
      the former are the public dose caused by the use of coal ash and the occupational
      exposure caused by radon and its progeny in coal mines. The total health risk
      (but excluding low probability/high consequence accidents) of the coal-fired
      energy chain, 57.1 deaths (GW a)(-1), is about 12 times of that of the nuclear
      energy chain, 4.6 deaths (GW a)(-1). The health risk of coal-fired energy chain
      could be significantly reduced if technique and management were improved. Even
      then the risk of the coal-fired energy chain is about 4.4 times that of the
      nuclear energy chain.

PMID- 9594115
TI  - The significance of variations in the angular correction factor in in situ gamma
      spectrometry.
AB  - In situ gamma spectrometry is a powerful method of assessing radioactive
      contamination in soil. The most widely adopted calibration methodology relates
      the overall sensitivity of the detector system to the product of three
      calibration factors: (a) the flux at the detector per unit activity in the ground
      phi/S(A), (b) the detected count-rate per unit flux incident normally at the
      detector N0/phi and (c) a correction factor to take into account the angular non
      uniformity in response of the detector (Nf/N0). The dependence of the latter
      factor on the activity distribution with soil depth is generally neglected
      despite the lack of published evidence to support this. By (i) modelling and (ii)
      use of published experimental profiles, this work examines the range of Nf/N0
      values likely to be encountered in the field. It was found that the use of a
      fixed angular correction factor is justified given that the maximum errors in the
      derived activity concentration do not exceed 5% and are far outweighed by other
      uncertainties.

PMID- 9594116
TI  - British Committee on Radiation Units and Measurements: RBE values for the
      retrospective calculation of risk to specific organs as a result of neutron
      irradiation.

PMID- 9594117
TI  - IAEA/WHO International Conference on Low Doses of Ionizing Radiation: Biological
      Effects and Regulatory Control, Seville, Spain, 17-21 November 1997 (IAEA-CN-67).
      International Atomic Energy Agency.

PMID- 9594118
TI  - SRP meeting--Medical Exposures, Health Surveillance and the Medical Exposures
      Directive held at the Cavendish Conference Centre London on 5 November 1997.

PMID- 9594119
TI  - Skill mix and workforce planning: is it time to open up the debate?

PMID- 9594120
TI  - The effectiveness of cardiac rehabilitation.
AB  - Factors influential in the occurrence and timing of heart attacks are summarised.
      Patients' and partners' experiences of heart attack are reviewed. Evidence is
      presented for the efficacy and effectiveness of cardiac rehabilitation
      programmes. A three elemental model for cardiac rehabilitation is introduced. Key
      recommendations are made for hospitals running cardiac rehabilitation programmes.
      Directions for the future development of cardiac rehabilitation are suggested

PMID- 9594121
TI  - Coping with critical illness: the child in the ICU.
AB  - The admission of a child to the intensive care unit (ICU) is stressful for both
      the child and his family. Children are especially vulnerable to the psychosocial
      stressors associated with life-threatening illness and hospitalisation. The
      child's developmental immaturity may affect his ability to cope. Priority may be
      given by nursing staff to the child's physical care. Nursing care is only
      complete with consideration of the total needs of the child and family. Meeting
      the child's psychosocial needs will promote development and adaptation to
      critical illness and provide more holistic care for the family.

PMID- 9594122
TI  - The advanced nurse practitioner in the ITU. A personal perspective.
AB  - An attempt is made to define the role of the Advanced Nurse Practitioner (ANP).
      Implications of Post-Registration Education and Practice (PREP) (UKCC, 1990), The
      New Deal (NHS Management Executive, 1992) and The Scope of Professional Practice
      (UKCC, 1992) are considered. Advanced traditional and practical nursing skills
      are reviewed. An opportunity for professionalism and increased autonomy for
      nurses is explored.

PMID- 9594123
TI  - The needs of relatives during the patient's stay in intensive care following
      routine cardiac surgery.
AB  - The review outlines and discusses the original study carried out by Molter (1979)
      which explored the needs of relatives in the intensive care setting. It explores
      studies which have replicated and developed the knowledge generated by Molter's
      study in both USA and UK. The needs of relative are endless and individual and
      must be set within the context of the family. There appears to be some dissonance
      between relatives' perceptions of their needs and nurses understanding and
      ability to meet their needs. Communication and creation of a therapeutic
      relationship between nurses and relatives is fundamental to the provision of
      holistic care. There are few studies which have focused on relatives within the
      cardiothoracic intensive care setting.

PMID- 9594124
TI  - Progression towards a 'no manual lifting' policy within the intensive care unit.
AB  - Nurses within the critical care environment are at increased risk of back injury,
      due to the high dependence of the patients. A move towards a 'no manual lifting'
      policy is desirable to reduce the costs of staff sickness, compensation claims
      and to comply with new legislation. Implementation of a 'no manual lifting
      policy' within intensive care poses a unique challenge due to the special needs
      of the critically ill patient. The call has gone out to avoid all manual lifting
      in all but exceptional and life-threatening situations.

PMID- 9594125
TI  - The communication gap in the ICU--a possible solution.
AB  - Presentations by nurses on ward rounds was introduced to improve
      multidisciplinary collaboration in the development of quality patient care. A
      second objective was to reduce nurses' passivity on the medical ward round and
      encourage them to play a more active role. Two questionnaires ascertained nurses'
      views, the first on implementation of presentations, and again after 6 months'
      active participation. Nurses were originally apprehensive about their new role,
      but then became aware of the positive aspects that the change brought to their
      working environment. The implications for medical staff were also considered.

PMID- 9594126
TI  - Intracranial pressure monitoring: nursing in a district general ICU.
AB  - Factors influencing intracranial pressure are summarised. The Codman subdural
      bolt is presented as a useful tool for monitoring intracranial pressure in a
      district general hospital. Implications for nursing care of patients with a
      Codman subdural bolt are discussed.

PMID- 9594127
TI  - Care of a patient requiring intracranial pressure monitoring.
AB  - The use of a Codman bolt is described in a 14-year-old head-injured boy. The
      benefits of the Codman bolt in permitting titration of nursing actions against
      rises in intracranial pressure are highlighted. Arguments for retaining head
      injury patients in a general ICU with intracranial pressure monitoring are
      weighed against the dangers of transfer.

PMID- 9594128
TI  - Imparting the knowledge of impending death to the intensive care patient who is
      unable to respond.
AB  - Silence during death is a communication deficit in the care of dying patients. In
      the ICU, patients are often unable to communicate, but may still be able to hear.
      Giving information of impending death to such patients is, therefore, done
      without their consent. Such information could be beneficial in enabling them to
      face death. Alternatively, it could cause emotional turmoil. Telling patients
      they are dying may help relatives to begin the grieving process. Guidelines are
      proposed to help nurses wishing to impart knowledge of impending death to their
      patients.

PMID- 9594129
TI  - The care of critically ill children in adult ICUs: the way forward.
AB  - It is unlikely that in the short or medium term the PIC service can be
      restructured to such an extent that no children would need to be admitted to an
      adult ICU. Until this is the case the contribution of adult ICUs to the provision
      of PIC should be acknowledged and formally recognised as part of the service.
      Furthermore, there should be active support for these units from major/regional
      centres. There are clearly only a few adult ICUs which admit significant numbers
      of children. However, a more detailed analysis of adult ICUs is required to
      identify units which have available the full range of facilities, support
      services and appropriate staff to care for critically ill children. It is likely
      that only a few adult ICUs could meet the recommendations above, and it is in
      these units where efforts need to be concentrated. It is imperative that any
      nationally agreed standards or guidelines for PIC must apply equally to both
      adult ICU and paediatric ICU.

PMID- 9594130
TI  - A study to investigate the needs of relatives of patients on a cardiothoracic
      ICU, following routine cardiac surgery.
AB  - The purpose of this study was to investigate the needs of relatives of patients
      on a cardiothoracic ICU, as perceived by themselves. An exploratory research
      design was used--a modified replication of a study carried out by Molter (1979)
      in the USA. Data were collected from a sample of convenience consisting of 14
      relatives of patients who had been on a cardiothoracic ICU, following routine
      cardiac surgery. Subjects were presented with a list of 45 need statements, which
      they were asked to rank by importance, to identify whether they perceived these
      needs to have been met, and to determine who was involved in meeting these needs.
      Data were analysed by the chi-squared test. The 12 most important needs were all
      perceived to have been met 64.3% or more of the time. Most needs were met by
      nurses.

PMID- 9594131
TI  - Cooling hyperthermic and hyperpyrexic patients in intensive care.
AB  - It is important for the Critical Care Nurse to respond quickly and appropriately
      to a rise in body temperature in a critically ill patient. A high temperature can
      impair both external and internal respiration, thus reducing oxygenation, cardiac
      output, lowering blood pressure and stimulating vasoconstriction. Accurate
      nursing assessment determines the appropriate cooling intervention. Hyperthermia
      involves a dysfunction of thermoregularity responses and responds best to
      physical cooling methods. Hyperpyrexia involves normal thermoregularity responses
      responding at a higher level. Hyperpyrexia responds best to central cooling
      interventions such as antipyretic therapy. Tepid sponging and ice cool packs are
      not recommended as they induce shivering and vasoconstriction. The need for more
      comprehensive research studies into cooling those receiving intensive care is
      needed.

PMID- 9594132
TI  - Cerebral oedema in fulminant hepatic failure.
AB  - Cerebral oedema is a common cause of death in patients with fulminant hepatic
      failure (Brajtbord et al, 1989). The relationship between cerebral oedema and
      fulminant hepatic failure is reviewed. The current diagnosis and treatment of
      cerebral oedema is discussed. Intracranial pressure monitors allow for early
      detection and treatment of cerebral oedema. Further research is required to
      evaluate the efficacy of each method.

PMID- 9594135
TI  - Pitfalls of preceptorship and the needs for adequate supervision.
AB  - This article provides a reflective account of an 'everyday' experience for three
      nurses in a cardiac high dependency unit. It discusses poor practices associated
      with preceptorship and illuminates the problems of developmental supervision for
      all levels of staff. The paper is a commentary on a nursing culture where
      anxieties are uncontained, creating difficulties for the development of advanced
      nursing practice and reflective practice.

PMID- 9594133
TI  - Brain stem death and organ donation.
AB  - Our understanding of the concept and definition of death has changed over time.
      The British contribution to the body of knowledge on the diagnosis of brain steam
      death was the publication by the medical royal colleges (1976) of diagnostic
      criteria. Most literature and research which explores the knowledge and attitudes
      of nurses towards the concept of brain stem death is from the USA. Several issues
      which arise from the literature are discussed in relation to organ donation.
      Further UK-based research is required.

PMID- 9594134
TI  - Issues concerning patient advocacy: personal experiences.
AB  - Issues concerning patient advocacy and nursing advocacy are explored in relation
      to the nurse's role and the UKCC code of conduct. The author's personal
      experiences of being an advocate are described. Potential conflict between the
      nurse's role and doctor's role in relation to advocacy is identified. The best
      person to take on the role of patient advocate is discussed.

PMID- 9594136
TI  - [Rehabilitation: a constituent of stroke treatment].

PMID- 9594137
TI  - [New concepts in the treatment of ischemic stroke].

PMID- 9594138
TI  - [Accurate diagnosis of lung infarction].

PMID- 9594139
TI  - [A comparative study of quantification of morphological changes in intracranial
      and extracranial arteries between cerebral hemorrhage and infarction].
AB  - In order to compare the difference and similarity of the pathological changes in
      intracranial and extracranial arteries between cerebral hemorrhage (CH) and
      cerebral Infarction (CI), 120 autopsy cases were studied, including 42 cases of
      the CH, 58 cases of the CI and 20 cases of cancer as control. Medium sized
      intracranial arteries and their main branches, small sized intracerebral
      arteries, arterioles and extracranial carotid arteries (from 14 cases only) were
      examined with light microscopy. The ratio of lumen area to vessel area (LA-VA
      ratio) and the degree of narrowing of the vessels indicating the severity of
      arteriosclerosis were determined. Quantitative analysis was carried out with
      computer. The results were as follows: (1) The CH and CI patients had
      significantly lower mean LA-VA ratios of the medium intracranial arteries and
      their main branches, small intracerebral arteries and arterioles than the
      controls. (2) The CH patients had apparently lower LA-VA ratio of the small
      intracerebral arteries and arterioles than the CI patients. (3) The CI patients
      had significantly lower LA-VA ratio of the medium sized intracranial arteries and
      their main branches than the CH patients. Moreover, atherosclerotic narrowing of
      these vessels was also much more severe in the CI than in the CH patients. (4)
      Atherosclerotic narrowing of the extracranial carotid artery in the CI patients
      was slightly more severe than that in the CH patients. These data suggest that
      patients with cerebral stroke have frequently atherosclerotic lesions in the
      medium sized intracranial arteries and their main branches and sclerotic lesions
      in the small intracerebral arteries and arterioles. The principal lesion of the
      CH are in the small intracerebral arteries and arterioles, while those of the CI
      in the medium sized intracranial arteries and their main branches and sometimes
      in the extracranial carotid arteries.

PMID- 9594140
TI  - [A study on red blood cell immune function in patients with Guillain-Barre
      syndrome and multiple sclerosis].
AB  - In order to understand whether there is red blood cell (RBC) immune dysfunction
      and the relationship between RBC immune abnormality and clinical state in
      patients with multiple sclerosis (MS) and Guillain-Barre syndrome (GBS), RBC
      immune function and circulation immune complex (CIC) level were evaluated in
      patient with these two diseases by using RBC immune adhesion test. It was found
      that the rate of formation of red blood cell-C3b receptor-yeast rosette was
      significantly lower in patients with these two diseases before and after
      treatment than that in a control group (P < 0.01). The rate of formation of red
      blood cell-immune complex-yeast rosette and the CIC level in GBS group were
      notably higher than that in the control group (P < 0.05). Moreover, we observed
      that the immune functions in patients with severe GBS and active MS were
      different from those in patients with mild GBS and stable MS and the change of
      each immune index in GBS and MS patients was related with the degree of recovery
      and the clinical state. These results suggested that decreased capability of RBC
      immune adhesion in patients with GBC and MS may be one of factors causing these
      diseases.

PMID- 9594142
TI  - [Effects of different lowdoses of aspirin on platelet activation and the number
      of platelets in the patients with coronary heart disease].
AB  - The number of alpha-granule membrane protein 140 (GMP-140) molecules was detected
      by using specific monoclonal antibodies (125I-SZ-51) against GMP-140 in three
      groups of patients with unstable angina treated with aspirin 50 mg (n = 27), 150
      mg (n = 26) and 300 mg (n = 30) a day before and 7 days after treatment. The
      number of platelets was counted by using the routine method. The results
      indicated that the number of GMP-140 molecules decreased significantly and the
      number of platelets increased significantly after treatment with aspirin. With
      the increase of aspirin dosage the degree of these two changes increased (P <
      0.01, both) too. When 300 mg of aspirin was used, the number of GMP-140 molecules
      was lower than that in a control group of healthy subjects (P < 0.005) and the
      number of platelets reached that of the control group (P > 0.05). There was no
      difference on the immediate side effects when these three dosages of aspirin were
      used. The authors of the opinion are that it is rational to use 300 mg of aspirin
      to treat patients with unstable angina at the beginning.

PMID- 9594141
TI  - [The relationship between insulin resistance and angiotensin II and endothelins
      in patients with essential hypertension and coronary heart disease].
AB  - In order to find the relationship between insulin resistance and angiotensin II
      and endothelins in patients with essential hypertension and coronary heart
      disease, blood glucose and insulin were measured during OGTT. Their area under
      the curve were also calculated. Fasting angiotensin II and endothelins were
      measured in 35 patients with essential hypertension. 32 patients with coronary
      heart disease and 20 healthy subjects. The results revealed that both the
      patients with essential hypertension and coronary heart disease were insulin
      resistant. Insulin resistance was higher in essential hypertension than in
      coronary heart disease. The group with essential hypertension showed higher
      insulin concentration at 1 hour postload and also greater total secretion of
      insulin. In the two groups of patients, both the insulin level during OGTT and
      the area of insulin were significantly positively correlated with angiotensin II
      level. In patients with essential hypertension, the level of endothelins was
      positively correlated, with insulin level at 1 hour postload and the area of
      insulin. It is suggested that the interaction between insulin resistance and
      angiotensin II and endothelins might be involved in the development of essential
      hypertension and coronary heart disease.

PMID- 9594143
TI  - [Prognostic factors of primary liver cancer].
AB  - To investigate the prognostic factors of primary liver cancer (PLC) and improve
      the long-term results, 1,248 cases of PLC were analysed. Univariate analysis
      demonstrated that discovery approach, staging of PLC, original gamma-GPT,
      resection, radical resection, original AFP, tumor size, tumor number, and tumor
      capsule have very significant effects on prognosis of PLC (all P < 0.001);
      cirrhosis, HBsAg, local resection, and tumor embolus in portal vein were also
      significant difference (all P < 0.05); age, sex, original AFP, hepatitis, and
      differentiation of PLC cells were no significant difference (all P > 0.05).
      Multivariate analysis demonstrated that original gamma-GPT, radical resection,
      tumor size, and tumor number were the most significant prognostic factors (all P
      < 0.001). Some aspects improving long-term survival were discussed.

PMID- 9594144
TI  - [Gastric emptying and intragastric distribution of liquid and solid meal in
      patients with systemic sclerosis].
AB  - To evaluate the gastric emptying functions in patients with systemic sclerosis
      (SS), gastric emptying and intragastric distribution during emptying after a
      liquid-solid meal were studied by single photon emission computed tomography in
      11 patients without gut symptoms and in 17 healthy volunteers. In patient group,
      half emptying times both of proximal (pT50) and of total stomach (T50) for both
      meal components were significantly longer than in controls. There were
      significant relationships respectively between the T50 and the pT50 for both
      liquid and solid meal. Out of 11 cases, 9 had delayed T50 of solid, which were
      accompanied by delayed emptying of liquid in 8 patients. The prolongation of
      gastric emptying of solid correlated significantly with the duration of the
      disease. However, the changes of the activity-time curves in the distal stomach
      during emptying were not reaching significant level when compared to the
      controls. In conclusion despite no existence of any gut symptoms our SS patients
      present significant delayed gastric emptying, which may be correlated to the
      dysfunction of tonic contraction of the proximal stomach attributed to autonomic
      neuropathy.

PMID- 9594145
TI  - [Protective effect of angiotensin coverting enzyme inhibitor on renal function in
      normotensive non-insulin dependent diabetes mellitus patients with early diabetic
      nephropathy and microalbuminuria].
AB  - Fourty six cases of non-insulin dependent diabetes mellitus (NIDDM) with
      normotension and microalbuminuria (< 30 mg/24 h) were divided into groups A and
      B, and observed for about 2 years. Only group A was treated with perindopril 2 mg
      a day. We found that 2 years later glomerular filtration rate (GFR), effective
      renal plasma flow (ERPF) and filtration fraction (FF) in the two groups decreased
      markedly, but GFR and FF decreased more markedly in group B than in group A.
      Meanwhile, in group A urinary albumin excretion rate (UAER) and insulin
      sensitivity index (SI) decreased significantly and blood pressure was stable, but
      in group B UAER and blood pressure elevated significantly and SI was only
      slightly ameliorated (P > 0.05). The levels of serum triglycerides and
      cholesterol were not markedly different between the two groups during the 2
      years. These results indicate that ACEI may play a role in protecting the renal
      function in diabetic nephropathy, reduce the risk factors of atherosclerosis and
      improve SI. It is beneficial to retard the development of diabetic nephropathy
      and to protect in renal function with small dose of ACEI.

PMID- 9594146
TI  - [Nested polymerase chain reaction (PCR) and multiple cloned antibody capture PCR
      for the examination of serum hepatitis B virus DNA in negative hepatitis B
      surface antigen patients suffering from liver diseases].
AB  - In order to find out rapidly the causes of the liver diseases suffered by
      patients with negative hepatitis B surface antigen (HBsAg), nested polymerase
      chain reaction (PCR) and multiple cloned antibody capture PCR techniques were
      established to examine serum hepatitis B virus (HBV) DNA. By using both
      techniques along with the examination of hepatitis C virus (HCV) infection, the
      causes of chronic liver diseases with negative HBsAg were studied. It is found
      that nested-PCR can increase the sensitivity of single PCR more than 1,000 fold
      and multiple cloned antibody capture-PCR can detect concentration of HBV DNA as
      low as 0.1-0.01 pg/L. HBV DNA positive patients were found in 45.5%, 30.8%, 13.3%
      and 100% respectively of the patients suffering from liver cirhosis with negative
      HBsAg (group A, 22 cases), chronic hepatitis with negative HBsAg (group B, 13
      cases), normal subjects with negative HBsAg and positive hepatitis B core
      antibody (HBcAb, group C, 30 cases) and liver cirhosis with positive HBsAg and
      negative HBeAg (group D, 12 cases). HBV DNA can be also found in the serum of
      HBsAb positive patients and subjects supposed to be healthy, 81.8% and 53.8% of
      the patients were infected with HBV and/or HCV in group A and group B
      respectively. All these results suggest that nested-PCR and multiple cloned
      antibody capture-PCR are rapid and highly sensitive methods for detection of
      serum HBV DNA. HBV infection is an important cause of chronic liver diseases in
      patients with negative HBsAg. The causes of most of the HBsAg-negative chronic
      liver diseases are related with infection of viruses. The clinical significance
      of serum HBsAb in naturally infected patients should be reconsidered.

PMID- 9594147
TI  - [Detection of Epstein-Barr virus DNA in renal tissue from patients with
      interstitial nephritis].
AB  - In order to demonstrate whether Epstein-Barr virus (EBV) infection might play a
      role in the pathogenesis of interstitial nephritis as suggested by many scholars,
      EBV DNA was detected in twelve specimens of frozen renal biopsy tissue from
      patients with interstitial nephritis by using nest polymerase chain reaction
      (nest PCR). For comparison, frozen renal biopsy tissue from ten patients with
      minimal change disease was used as control. Southern blot hybridization was used
      to check the specificity of PCR product. The results showed that eight of twelve
      frozen renal biopsy specimens from interstitial nephritis patients were EBV DNA
      positive (66.7%), as compared with negative in all the ten frozen renal specimens
      from minimal change disease patients. The differences was statistically
      significant (P < 0.01). The study strongly suggests that EBV infection may play
      an important role in the pathogenesis of interstitial nephritis. The location of
      EBV in renal tissue and the mechanism inducing interstitial nephritis by EBV are
      to be clarified.

PMID- 9594148
TI  - [Consolidation therapy with high-dose cytarabine and daunorubicin for prolonged
      disease free survival in acute myelocytic leukemia].
AB  - In order to study the effect of consolidation therapy with high-dose cytarabine
      (Ara-C) and daunorubicin (DNR) for prolonged disease free survival (DFS) in acute
      myelocytic leukemia (AML), 51 patients with AML in remission were treated with
      this method. Ara-C at a dosage of 1.3g/m2 administered in 2-hour intravenous
      infusion every 12 hours for 10 doses. After the treatment of Ara-C, DNR was given
      at a daily dose of 45 mg/m2 in rapid intravenous infusion for two days. The
      median duration of complete remission (CR) was 32 (8.2-110) months. The duration
      of DFS was more than 3 years in 21 patients (41.18%) and more than 2 years in 35
      (68.63%). In a control group, however, the median duration of CR was 10 months
      and the rates of patients with DFS more than 3 and 2 years were 12.5% and 21.8%
      respectively. It is shown that high-dose consolidation chemotherapy is an
      effective method to prolong DFS in patients with AML. Toxicities of high-dose Ara
      C and DNR can be tolerated by patients with AML.

PMID- 9594149
TI  - [Apoptosis and cerebral ischemia].

PMID- 9594150
TI  - [Positron emission tomography in the diagnosis and treatment of cardiovascular
      diseases].

PMID- 9594151
TI  - [Current status and prospects of liver surgery in China].

PMID- 9594152
TI  - [Long-term results of multimodality treatment in patients with primary liver
      cancer].
AB  - This paper report the long-term results of multimodality treatment in 2388
      patients with pathologically proven primary liver cancer (PLC) over the last
      three decades. The 5-and 10-year survival after resection of PLC was 39.3% and
      29.2% respectively for the whole series (n = 1650), and 61.9% and 45.4%
      respectively for patients with small PLC (< or = 5 cm, n = 569). The 5-year
      survival after cryosurgery was 37.9% for the whole series (n = 191), and 53.1%
      for patients with small PLC (n = 56). The 5-year survival of 71 patients
      receiving sequential resection after cytoreduction therapy was 66.0%. The 5-year
      survival after re-resection for recurrence tumor (n = 147) was 34.5%. 214
      patients survived more than 5 years; of these 113 patients (52.8%) were small
      PLC, and 57 patients survived more than 10 rears. It is concluded that early
      detection and resection of small PLC is the leading approach to get long-term
      survivors, cytoreduction and sequential resection might be an important approach
      to improving the prognosis of patients with unresectable PLC, re-resection for
      subclinical recurrance and metastasis after an initial curative resection was
      also important to prolong survival further.

PMID- 9594153
TI  - [Treatment of irresectable hepatocellular carcinoma with repeated transient
      dearterialization].
AB  - A joint clinical prospective study between SUMS and Lund university was reported.
      40 patients with the irresectable hepatocellular carcinoma (HCC) admitted to the
      department of HPB surgery in the First Affiliated Hospital of SUMS were
      randomized into two groups: (20 each) from Feb. 1994 to April, 1995. The patients
      were treated with hepatic artery ligation (HAL) and repeated transient
      dearterialization (RTD) respectively. Postoperative response to treatment, liver
      function change (ALT), AFP, imaging examination of the tumor, patient's survival
      were evaluated. It has been shown that RTD is superior to HAL in terms of the
      objective response to the therapy, reduction of tumor size, patient's symptom
      relief, liver function and AFP changes and patient's survival. In the RTD group,
      the effective rate was 70%, the mean survival time was 8.2 months, and the 6
      month survival rate was 79.7%. In HAL group, the effective rate was only 5%, the
      mean survival time was 5.1 months, 6 months survival rate was 35.8%. It has been
      postulated that RTD may prevent the rapid development of collateral circulation
      and increase the production of oxygen-derived free radicals, which may be the
      responsible factors for the ischemic treatment of hepatic tumours. We consider
      that RTD would be a promising polliative method for HCC.

PMID- 9594154
TI  - [Radioembolization with 32P-labelled glass microspheres for advanced
      hepatocellular carcinoma].
AB  - We evaluated the efficacy and side effect of 32P-Labelled glass microspheres (32P
      GMS) as a radioembolizer for patients with advanced hepatocellular carcinoma
      (HCC). 24 patients with unresectable HCC received internal radiation treatment of
      32P-GMS. The tumor size varied from 3.6 to 18 cm. Hepatic arterial embolization
      was carried out through intraoperative or Seldinger's method. The mean absorbed
      radiation dose of the liver was 3250 rad (range from 1200 rad to 8000 rad). The
      radiation intensity within the tumor was 3.3 times stronger than in liver tissue.
      Not significant bone marrow renal toxicity was noted within 1 to 3 months. > 50%
      of tumor shrinkage was found in 17 cases, and < 50% of tumor reduction in 5
      cases. The cumulative survival rate of 3, 6, 12, 18, 24 months was 92%, 75%, 54%,
      33% and 29%. Hepatic arterial instillation of 32P-GMS appears to be safe and
      effective for unresectable HCC even with portal vein thrombosis.

PMID- 9594155
TI  - [Anti-human AFP variant McAb in radioimmunodetection for primary hepatocellular
      carcinoma].
AB  - We investigated the affinity and special combination of anti-human AFP variant
      monoclonal antibody (AFP-R-LCA McAb) for cells of AFP positive hepatocellular
      carcinoma (HCC). AFP-R-LCA McAb was labeled by 131I radioisotope (131I-AFP-R-LCA
      McAb injected into the peripheral veins of patients with HCC or liver cirrhosis
      after hepatitis B. 131I-AFP-R-LCA McAb was gathered in tumor of HCC in 6 AFP
      positive patients, but there was no positive gathering in HCC in 6 AFP negative
      or 4 liver cirrhosis patients. AFP-R-LCA McAb has strong affinity and special
      combination to AFP positive cells of HCC and can be recognized as a carrier for
      radioimmunodetection and radiommunotherapy.

PMID- 9594157
TI  - [Bioartificial liver].

PMID- 9594156
TI  - [Experimental study on homoiothermic extracorporeal liver preservation].
AB  - To prove that perfused liver can be preserved at room temperature (22 degrees C),
      we made the experiment, in which HTK was basic solution, perfluorocarbon acted as
      oxygen carrier and lipid acted as energy substrate in the homoiothermy condition,
      pig liver organs were perfused extracorporeally through the V. portal with
      perfusion solution. In fixed period of time the perfusion solution from the liver
      was taken and analysed to determine for liver biochemical function and observe
      the concentration and size of hepatocellular mitochondria. In oxygen carrier
      perfusion solution the ammonia concentration was low, urea concentration was
      high, damage to mitochondria was minimum and by addition of lipid emulsion the
      concentration of glucose can be maintained. The experimental and control data
      were obviously significant. The result demonstrated that oxygen carrier
      (perfluorocarbon) as oxygen supplier can provides enough oxygen to liver cell, at
      the sametime, lipid emulsion intralipid) provides energy so as the perfused liver
      can be preserved at high temperature, i.e. 22 degrees C at relative long time (40
      hours) and still has the function of removing toxic substance such as ammonia and
      converting it to urea, meanwhile maintain the normal structure of mitochondria.
      The preservation of perfused liver at homoiothermy is possible.

PMID- 9594158
TI  - [Video assisted thoracoscopic thymectomy for myasthenia gravis].
AB  - Thymectomy is now an established approach to the treatment of myasthenia gravis
      (MG). We used video assisted thoracoscopic surgery (VATS) in thymectomy. From
      June 1993 to May 1995, we performed VATS thymectomy for 10 cases (6 males, 4
      females with age ranging from 9 to 76 years). Complete thymectomy was achieved in
      every case by examination of the thymic bed and resected specimen. There was no
      mortality and complications were few. Average hospital stay was 4.1 days.
      Compared with the conventional median sternotomy approach, VATS was associated
      with a shorter postoperative hospital stay and analgesic requirement. We believe
      that VATS thymectomy is technically feasible. However, its true role in the
      treatment of MG requires further study.

PMID- 9594159
TI  - [Unroofed coronary sinus syndrome].
AB  - Unroofed coronary sinus syndrome or coronary sinus septal defect is a rare
      congenital cardiac anomaly. We performed corrective operations in 9 patients with
      such condition. Of them, seven patients had the completely unroofed coronary
      sinus and persistent left superior vena cava (PLSVC) directly draining into the
      left atrium (LA). One patient had PLSVC and the partially unroofed terminal
      portion of the coronary sinus (CS), or sinus ostium open into LA. Another patient
      had total anomalous pulmonary vein connection and the partially unroofed mid
      portion of CS without PLSVC. The operative methods of the unroofed coronary sinus
      included: ligating PLSVC and repairing ostium primum or secundum atrial septal
      defects in 4 cases; creating an intra-atrial tunnel from PLSVC to the right
      atrium (RA) and repairing the atrial septal defect in 2 cases; reconstructing the
      intra-atrial septal with a patch as a baffle to guide PLSVC or sinus ostium
      respectively towards RA in 2 cases; enlarging the defect on the coronary sinus
      roof and repairing the atrial septal defect of the coronary sinus type in one
      case. No patient died in this group. Because unroofed coronary sinus syndrome has
      atypical clinical manifestation and usually complicates varied congenital
      anomalies, its preoperative diagnosis is very difficult in some times and may
      draw the reliable support from echocardiography and catheterization. The
      operative program and method must depend not only upon its type but also upon
      PLSVC presence of absence, and communication between PLSVC and RSVC.

PMID- 9594160
TI  - [In situ saphenous vein arterial bypass for lower limb ischemia].
AB  - 28 patients with 30 ischemic lower limbs were treated by in situ saphenous vein
      femorodistal arterial bypass using self-made valvulotome at Zhongshan Hospital
      from 1989 to 1994. All patients had claudication in the lower extremities and
      were diagnosed angiographically. The preoperative ABI was from 0 to 0.57 (mean
      0.41). All the vein grafts were patent postoperation and the dorsalis pedis or
      posterior tibial arteries were palpable in 18 legs immediately postoperation and
      the dorsalis pedis or comitant arterial reconstruction. Graft occlusion within 3
      days after original operations occurred in three cases and secondary surgical
      corrections were successful. Postoperative mean ABI increased from 0.41 to 0.84.
      The limb salvage rate was 100% and the cumulative patency rate, by the lifetable
      analysis in 1, 2, 3, 4 and 5 years, were 92%, 88%, 86%, 78% and 71% respectively.
      The results suggest that the in situ saphenous vein arterial bypass is the
      superior method for distal arterial reconstruction and concomitant procedures to
      ensure sufficient inflow as well as outflow are essential to the patency of the
      graft.

PMID- 9594162
TI  - [Clinical application of gamma nail in the treatment of the intertrochanteric
      fractures].
AB  - We retrospectively studied the clinical application of modified Gamma nail (GN).
      Based on the measurement of intramedullary canal of the femur by wax model. We
      modified GN in the following aspects: the diameter of GN was changed from 17 mm
      to 14 mm in the proximal end and from 13 mm to 10 mm in the distal end and the
      angle between the two ends was also modified from 11 to 5-6; the modified
      compression screws represented self-compression property; the long GN was
      designed and developed. We applied GN in 31 cases, and 28 with an average
      postoperative duration of 20 months were followed up. The final results revealed
      that the fracture healing rate was 93%. No crutch ambulance reached 86% and
      excellent hip movement reached 82%. The partial or complete weight bearing was
      allowed 9-11 days postoperatively. We consider GN an effective means for the
      treatment of type II and type III of intertrochanteric fracture of the femur.

PMID- 9594161
TI  - [Microsurgical treatment of cavernous sinus tumor].
AB  - We studied 25 cases of cavernous sinus tumors who underwent microsurgical
      operation. The tumors were mainly composed of neurinomas and meningiomas. The
      tumors of 8 of 9 cases of the former, and 4 of 6 cases of the latter were totally
      removed. None of the patients died. We discussed the operative, method,
      preoperative preparation and postoperative complication.

PMID- 9594163
TI  - [Monoclonal antibodies against transitional cell carcinoma assay tumor associated
      antigens in different grades bladder cancer patients].
AB  - Monoclonal antibodies (McAb) 19A211, M344 against transitional cell carcinoma
      (TCC) was used to assay the tumor associated antigens on paraffin-embedded tissue
      sections of 51 different grades bladder cancer patients with immunohistochemical
      stain method. The positive rates of 19A211, M344 antigens expression were 82.4%
      and 88.2% in 17 grade I patients 77.7% and 83.3% in 18 grade II patients, 37.5%
      and 37.5% in 16 grade III patients. 19A211 and M344 antigens expression in
      statistical analysis was as follows: 19A211, grade I/grade III, P < 0.01, grade
      II/grade II, P < 0.05, M344, grade I/grade III, P < 0.01, grade II/grade II, P <
      0.05, showed significant differences. Combined use of McAb 19A211 and M344 assay
      bladder TCC tumor associated antigens, showed that the positive rates of antigen
      expression in grade I was 100% (17/17), in grade II was 88.8% (16/18), in grade
      III was 68.8% (11/16). The results indicate that McAb 19A211, M344 were fit to
      diagnose grade I, II bladder TCC. Using both of two McAb can increase the
      positive rate in finding superficial bladder TTC.

PMID- 9594164
TI  - [Malignant fibrous histiocytoma of kidney].
AB  - Malignant fibrous histiocytoma of kidney is one kind of rare tumor. About 20
      cases have been reported abroad and 3 in this country. This kind of tumor is
      characterized by high malignancy and invasive growth. It is difficult to
      differentiate it from renal cancer by radiology. Fibroblasts stand in line as
      "storiform pattern" and touton giant cell can be seen under microscopy. The
      definite diagnosis can be made through immunohistochemistry.

PMID- 9594165
TI  - [The roles of Kupffer cell (KC) in reduction of post burn catabolism in early
      enteral feeding].
AB  - This study aimed to know the roles of Kupffer cells in post burn catabolism. Rats
      sustained with 30% III degrees flame burns of TBSA were divided randomly into
      early feeding (EF) group given gastroenteral feeding beginning from 2 hours
      postburn (n = 45), and delayed feeding (DF) group given the same nutritional
      solutions but starting on PBD3 (n = 45). Another 15 rats were served as normal
      controls (NS) without burning. The results showed that the bowel-barrier-function
      reduced obviously, the thickness of mucosa and height of villi of jujunum
      declined significantly and the plasma endotoxin level was higher in the DF group
      than that in the EF group. There were obvious increase of catabolic hormone
      (cortisol) level and decrease of anabolic hormone (insulin) level in plasma of
      the DF group than that of the EF group. The protein contents of jejunum mucosa
      and gastrocnemius decreased significantly, TNF and PGE2 released by KCs also
      increased more markedly in the DF group than that in the EF group. In conclusion.
      KCs may play one of the key roles in the "gut derived hypermetabolism". Early
      enteral feeding can enhance the barrier function of intestinal mucosa and prevent
      the translocation of endotoxin from gut to blood stream in some extent. Early
      enteral feeding can reduce catabolism via the modulation of hyperactivity of Kcs
      and the decrease of excessive secretion of catabolic hormones.

PMID- 9594166
TI  - [Changes of N-methyl-D-aspartate receptor in spinal cord after trauma].
AB  - N-methyl-D-aspartate (NMDA) receptor-mediated events have implicated in the
      pathophysiology of posttraumatic spinal cord injury. In the present study, [3H]
      CPP was used as ligand to analyse the changes in NMDA receptor-binding sites in
      synaptic plasma membranes (SPM) isolated from rat spinal cord after impact trauma
      at T10. Radio-binding assays of [3H] CPP showed a specific and saturable binding
      site for [3H] CPP in spinal cord tissue. Scatchard analysis revealed the binding
      of [3H] CPP has one site with low affinity (Kd = 3.51 < or = 0.26 nM) and binding
      density (Bmax = 662.82 < or = 47.59 fmol/mg protein). [3H] CPP binding to NMDA
      receptor at the thoracic segment was significantly (P < 0.01) decreased
      posttrauma. Time-course studies demonstrated significantly decrease in the
      binding of [3H] CPP at 4 h after spinal cord injury with recovery by 24 h.
      Scatchard analysis results indicate that the posttrauma decrease of [3H] CPP
      binding resulted from alteration in receptor binding density The data from the
      present study provided further evidence for a role for NMDA receptor-mediated
      mechanisms in the pathological consequences of spinal cord injury. The acute
      reduction in [3H] CPP-binding after trauma may reflect down-regulation of NMDA
      receptor as a consequence of posttraumatic glutamate release and may serve to
      limit excitotoxin-induced injury.

PMID- 9594167
TI  - [A direct transnasal transsphenoidal approach to pituitary tumors].
AB  - 38 cases of pituitary adenomas were resected via direct transnasal trans
      sphenoidal approach. Complete or subtotal tumor excision was achieved in 36
      patients, and partial excision in 2. The operative mortality was 0. The operative
      techniques were, in patients with small nostrile, a 5-6 mm small incision was
      made in the base of lateral alar, but the speculum straightly upon to the
      anterior wall of the sphenoidal sinus. As expanding the speculum, the middle
      septum was pressed to the opposite side. Under the operating microscope, the
      anterior wall mucose was dissected away, the bony wall drill off and then the
      sphenoidal sinus approached. Other steps were as usual. All cases achieved good
      result. The advantages of this approach were less destructive, less time
      concuming, less complications and easy to perform.

PMID- 9594168
TI  - [Os odontoideum].
AB  - Seventeen patients who had os odontoideum were reviewed. Among them occipito
      cervical fusion was performed upon 12 patients with atlanto-axial instability.
      All of them achieved fusion. The patients were followed up for 2 to 16 years and
      satisfactory results were demonstrated. We consider that surgical treatment is
      indicated when os odontoideum is combined with atlanto-axial instability.

PMID- 9594169
TI  - [Failure and complication following surgical treatment of scoliosis: analysis of
      101 cases].
AB  - Complications occur frequently after surgical treatment of scoliosis. In order to
      prevent from them effectively, 101 cases with failure and postoperative
      complications were analysed. They included rod fracture in 22 cases (15
      Harrington rods, 4 Zielke rods, and 3 Luque rods); recurrence of curve severity
      in 12 cases; broken or loossened luque wires in 15 cases; loss of thoracic
      kyphosis (flat back) in 6 cases; progressive kyphosis with or without paraplegia
      following incorrect posterior decompression in 5 cases; and increased unbalance
      of shoulders after instrumentation in 2 cases due to neglect of the tilting of
      the first thoracic vertebra. Infection occurred in 8 cases (incision infection 7
      cases; deep wound infection in 1 case); and pneumothorax in 1 cases. They were
      induced by biomechanical factors in 23 cases (22.77%), incorrect selections of
      indications in 29 cases (28.71%), oprational mistakes in 37 cases (36.63%),
      internal fixation factors in 15 cases (14.85%). The authors hold that there are
      quite a lot of factors leading to occurrence of complications and the effective
      way for prevention from them is to understand the factors and main technical
      points related to internal fixation.

PMID- 9594170
TI  - [Three-dimensional recons-truction of lumbar-sacral canal and its contents:
      experimental study].
AB  - In order to suit the needs of studies in spinal column surgery on three
      dimensional spatial structure and morphology of lumbar-sacral canal and the
      nervous tissue within it, an experimental model was applied by the authors using
      lumbosacral specimens from two fresh young adult cadavers. Successive 2mm thick
      CTM screening was carried out from L3 to S2 vertebral bodies with an interval of
      1mm. The serial two-dimensional CT photographical pictures so obtained were
      inputted into a computer and the three-dimensional images were reconstructed
      through a VIDAS image analysis system. The experimental results indicated that
      the three-dimensional images of reconstructed vertebral canal and the nervous
      tissue within it were lifelike. These images could not only reveal their three
      dimensional structure and morphology, but also be cut and composed together at
      any direction and section by turning and transpositioning along X, Y and Z axes.
      The authors hold that the visual effect expressed by three-dimensional images
      reconstructed from two-dimensional pictures can play important role in
      stereomorphologic, biomechanical, and other studies in fields of anatomy, image
      analysis, and clinical medicine.

PMID- 9594171
TI  - [Ankylosing spondylitis and heterogenity of HLA-B27 in Chinese].
AB  - HLA-B27 represents a family of closely related antigens. More than six alleles
      differing in limited number of nucleotide substitution had been described (B2701
      B2706). We subtyped HLA-B27 in 76 patients with ankylosing spondylitis (AS) and
      1200 Chinese healthy persons of Han nationality. Polymerase chain reaction was
      designed to amplify specific regions for class I (exon 2 and 3). Amplified
      sequences were tested with eight sequence-specific oligonucleotides to
      distinguish all HLA-B27 subtypes. The results showed: the HLA-B27 was closely
      related with AS and at least four subtypes existed in Chinese patients. B2704 was
      the most common subtype occurring in 54.8% and 50.85% respectively in HLA-B27
      positive AS patients and healthy controls. The main HLA-B27 subtypes in the HLA
      B27 positive patients distributed in similar proportion to that of HLA-B27
      positive healthy controls (P > 0.1). We believe that the above results imply that
      the prevalences of the various subtypes of HLA-B27 vary in different races. The
      HLA-B27 specific residues that are shared by the subtypes might be involved in
      the pathogenesis of AS.

PMID- 9594172
TI  - [Prevention from secondary nerve root adhesion: an experimental study].
AB  - In the study, 27 dogs were divided into three groups: A, B and C. Then all of the
      dogs had their lumbar intervertebral disks removed. Into the wounded cavity of
      group A, 1 ml of dimethicone was dropped and gelatin sponge was applied on the
      surface of the nerve root of group B. Group C was served as the control. The dogs
      were killed and the operation area was removed respectively 2 weeks, 4 weeks, and
      12 weeks after the operation for macroscopical observation, nerve root motility
      measurement and histological examination. The result of the experiment proved
      that dimethicone was fairly effective in the prevention from secondary nerve root
      adhesion. While gelatin sponge in the process of its absorption induced the
      formation of quite a few scar tissues, thus aggrevating nerve root adhesion.

PMID- 9594173
TI  - [Prevention of peridural fibrosis and adhesion after laminectomy: an experimental
      study in rats].
AB  - An experimental study on the effectiveness of various materials including poly
      carboxymethylcellulose (PCMC), gelatin foam (GF), ligment (L), free fat (FF) in
      prevention of peridural fibrosis and adhension (PDA) was done in 144 SD rats
      using a total laminectomy model (L1-2). PDA was measured with a double-blind
      protocol at 2, 4, 8, 12 weeks postoperatively by gross anatomical appearance
      (blunt-dissection), microscopical evaluation, computed imaging analysis and MRI
      enhanced with gadolinium. The results demonstrated that the peak of PDA is within
      8 weeks after operation. PCMC, as a three dimensional protective material, could
      effectively inhibit PDFA after laminectomy, but GF and L could not. SHA had some
      effect in the early stage, but not in the late period. For FF though it could
      effectively prevent PDA, the incision infection rate was higher, the atrophy and
      necrosis of FF were serious. What is more, almost all transplanted fat remained
      in situ extended into the spinal cord in some measure after 8 weeks
      postoperatively.

PMID- 9594174
TI  - [Prevention of epidural scar adhesion following lumb spine operation].
AB  - Four biomaterials including pork fat (PF), glutaradehyde crosslinked pork
      peritonium (GCP), glutaradehyde cross-linked human amnion (GCA) and freeze-dried
      human amnion (FDA) dura were compared for their ability to prevent the dura from
      adhesion in 24 dogs. Noncontiguous laminectomies were performed on each dog.
      Laminectomized areas where the above mentioned 4 materials put randomly were
      served as experimental groups while laminectomized areas with autologous fat
      transplants put in place were served as standard control and empty control was
      set with the area left untreated. The formation of fibrosis and the adhesion of
      the dura were evaluated at 1, 2, 3, 4, 6, 12 weeks after operation by using a
      double-blind protocol. Methods of observation included gross anatomical
      evaluation, histological evaluation, computer-assisted image analysis,
      fibroblasts counting and measurement of SCEP. The results showed: 1. The epidural
      scar arose from the raw surface of erector spinal muscles and the bony edges
      created by the procedure; 2. Putting a suitable obstructor between the dura and
      the erector spinae muscle would make dura be exempted from adhesion; 3. The
      interpositional membrane should be tucked in between the bony edges in close
      proximity to the bony surface without leaving any room; 4. GCA seems to be
      efficient in preventing dural adhesion and reducing the invasion of the scar
      tissue in the spinal canal.

PMID- 9594175
TI  - [Management of coagulation dysfunction in critically surgical patient].
AB  - 12 surgical critically ill patients were studied for a better management of
      perioperative coagulation dysfunction. Their primary disease, clinical
      manifestation as well as some coagulation tests before and after therapy were
      retrospectively analysed. The result showed that secondary disseminated
      intravascular coagulation (DIC) is the main type of perioperative coagulation
      disorder, especially in decompensated hepatopathy and severe sepsis patients. It
      should be emphasized that: control of primary disease, effective drainage of
      focus, strict indication for 2nd surgical hemostasis and correct operation are
      required. For those hepatopathy with hypofibrinogenemia, some hemostatic drugs
      should be prohibited or very carefully used, in order to avoid the activation of
      plasmin and the exhaustion of fibrin. The early administration of heparin and
      aprotinin after the supplement of fibrinogen has shown a great potential benifit
      to stop the cascade of hypercoagulation and hyperplasminogenemia by enhancing the
      level of AT-III and fibrinogen in plasma.

PMID- 9594176
TI  - [Pathological study on the metastatic routes of bile duct carcinoma].
AB  - Multiple staining was performed on resected tumors. Samples after curative
      surgery in 40 cases of bile duct carcinoma for observation of tumor blood vessel
      density (TVD), and perineural invasion index (PNI). Lymphatic invasion was found
      in 29 cases (72.5%), blood vessel invasion in 31 (77.5%), and PNI in 33 (82.5%).
      TVD and PNI were positively correlated with metastasis. Three years after
      operation, the recurrent rate was 100%, with an averaging recurrent time of 9.6
      months in the metastatic group in contrast to 64.3% and 17.5 months in those
      without metastasis.

PMID- 9594177
TI  - [Diagnosis and surgical management of pancreatic pseudocysts].
AB  - Fifty-two patients with pancreatic pseudocysts were treated surgically between
      1968 and 1994. Clinical symptoms were non-specific. Ten patients with acute
      pancreatitis were managed conservatively and resolution occurred in 3 patients.
      42 patients underwent operation. Internal drainage was performed in 28 patients,
      external drainage in 8, others in 6. Pancreatic fistulas occurred in the external
      drainage group, 2 patients died and 1 patient had the of recurred pseudocyst.
      There were no complications in the internal drainage group. It was quite
      different in the external drainage group. The management should differ in that
      acute and chronic pancreatic pseudocysts. Patients with pseudocysts of chronic
      pancreatitis could undergo emergent surgery of internal drainage because waiting
      6 weeks for maturation of the pseudocysts after diagnosis was unnecessary and
      even hazardous. However, if pseudocyst developed after acute pancreatitis, it
      should be watched for up to 6-8 weeks. During this period the pseudocyst perhap
      disappeared spontanously or matured for surgery.

PMID- 9594178
TI  - [Management of subclavian artery aneurysm].
AB  - The subclavian artery aneurysm is not a commonly seen peripheral aneurysm. We
      treated 7 cases in recent 13 years. There were 4 tramatic pseudoaneurysms and 2
      atherosclerotic aneurysms. Four aneurysms were resected and replaced by PTFE or
      Dacron vascular prostheses. Two were treated by arterial repair. Good long-term
      outcome was obtained.

PMID- 9594179
TI  - [Comprehensive treatment of intracranial aneurysm complicated by postoperative
      vasospasm].
AB  - Forty six patients suffered from intracranial aneurysm complicated by
      postoperative vasospasm and delayed cerebral ischemia were monitored dynamically
      both by clinical observation of neurologic status and multiple items such as
      transcranial Doppler, serum osmolality, intracranial pressure and other somatic
      physiologic items related to monitoring. Patients were intensively and
      comprehensively treated according to individualized grading of vasospasm. Forty
      four patients (95.6%) were completely recovered from postoperative vasospasm and
      delayed cerebral ischemia, while 2 patients (4.3%) complicated by hemipalsy as a
      consequence of delayed cerebral ischemia. The occurrence of vasospasm and delayed
      cerebral ischemia, the criteria of TCD grading, the valuableness of multiple
      physiologic items and problems related to comprehensive treatment are discussed.

PMID- 9594180
TI  - [Therapeutic effect of THAM on lactic acidosis of severe brain injury].
AB  - The presence of lactic acidosis in the cerebral spinal fluid of 50 patients with
      severe head injury was studied. The GCS scores of these patients were < or = 8.
      The patients were divided into two groups. We treated 25 patients with a dose of
      4 to 5 ml/kg of THAM infused intravenously 2 to 3 times for daily administration.
      Other 25 patients who were not treated with THAM served as a control group. In
      each case, a ventricular pressure monitoring device was installed. The ICP was
      the contineously recorded. In addition, laboratory study, including lactate, pH,
      HCO-3 and BE in CSF was performed. THAM infusion was associated with improved
      survival, decreased ICP as compared to that in the control group. We believe that
      THAM treatment may significantly improve the prognosis of presence of lactic
      acidosis as a result of severe head injury.

PMID- 9594181
TI  - [Influence of age on serum prostate specific antigen concentration].
AB  - 322 men who had not prostatic diseases were selected at random for defining the
      characteristics of serum prostate specific antigen (PSA) in order to use PSA more
      appropriately in detecting clinically significant prostate cancer. The serum PSA
      concentration is correlated with patient age (r = 0.301; P < 0.0001), PSA is
      increased with age. The recommended upper limits (mean +2 standard deviations)
      for serum PSA for men aged 20-49 years was 2.71 ng/ml; for 50-59 years,
      5.01ng/ml; for 60-69 years, 6.05 ng/ml; and for greater than or equal to 70
      years, 7.92 ng/ml. Our findings led to proposals for using age-specific PSA
      reference range instead of a single reference range for men of all age groups.
      These age-specific reference ranges have the potential to increase the
      specificity of using PSA for detecting prostate cancer.

PMID- 9594182
TI  - [Glutamine dipeptide attenuate mucosal atrophic changes and preservation of gut
      barrier function following 5-FU intervention].
AB  - Traditional parenteral nutrition (PN) and chemotherapy may lead to changes
      mucosal morphology and gut barrier function. To investigate the effects of alanyl
      glutamine on intestinal mucosal morphology and gut barrier function in PN-fed
      rats challenged with 5-FU male Wistar rats were central catheterized and
      randomily divided into two groups: PN group (n = 10) that received traditional
      parenteral nutrition solution only, and Ala-Gln group (n = 10) that received
      glutamine dipeptide enriched nutritional solution (3% Ala-Gln). The rats were
      maintained on their respective diets for 7 days. 5-FU (75 mg/kg) was injected
      intraperitoneally at 8 am on day 4. All rats were gavaged with lactulose (100 mg)
      and mannitol (50 mg) in 2ml before and three days after administration of 5-FU.
      Ala-Gln group maintained serum glutamine concentration, intestinal mucosal
      morphology. While bacterial translocation rates in ala-Gln group was 30%, in PN
      group was 90% (P < 0.05). Similar intestinal permeability was observed on day 3
      in both groups. The control group had a significantly increased intestinal
      permeability on day 7 (P < 0.05), while Ala-Gln group maintained the intestinal
      permeability. It was suggested that alanyl-glutamine maintained intestinal
      morphology and gut barrier function in PN-fed rats challenged with 5-FU.

PMID- 9594183
TI  - [Effects of hypertonic sodium lactate dextran resuscitation in severely burned
      dogs].
AB  - 12 dogs with 35% TBSA third degree burns received HLD resuscitation (HLD group, n
      = 6) or LR resuscitation (LR group, n = 6). Fluid resuscitation started one hour
      postburn. The amount of fluid infused with HLD resuscitation was calculated by
      that after giving HLD 19.6 ml/kg in 3 hours and 6 ml/kg/% TBSA lactate Ringer's
      solution followed. The amount of fluid infused with LR resuscitation was
      calculated by 8 ml/kg/% TBSA lactate Ringer's solution. Infusion of lactated
      Ringer's solution in both groups was adjusted by maintaining urinary output 0.5-1
      ml/kg/h. The volume of fluid infused in HLD group (5.05 +/- 1.11 ml/kg/% TBSA)
      was much less than that of LR group (10.03 +/- 1.30 ml/kg/%TBSA) (P < 0.01).
      There was no significant difference in urinary output, serum Na+ and albumin, and
      plasmacrystalloid osmolarity between two groups. Plasma level of MDA decreased
      after resuscitation with HLD, which (0.81 +/- 0.20 mmol/g Hb) was much lower than
      that (1.39 +/- 0.44 mmol/g Hb) of LR group 4 hours postburn (P < 0.05). Plasma
      SOD activity (7.22 +/- 0.68 u/g Hb) of HLD group were much higher than that of LR
      group (4.86 +/- 0.53 u/g Hb) 4 hours postburn (P < 0.05). HLD resuscitation could
      significant reduce the amount of fluid infused comparing with lactate Ringer's
      solution. HLD resuscitation could attenuate postburn damage to tissue induced by
      lipid peroxide by elevating plasma SOD activity.

PMID- 9594184
TI  - [The role nitric oxide and other neurotransmitter in canine penile erection].
AB  - The role on nitric oxide and its relative factors (cGMP, cAMP, methylene blue)
      was studied in canine erection induced by stimulating pelvic nerves, and the
      effect of cholinergic neuroeffectors and the sinusoidal endothelium was also
      observed in this experiment. The results indicate that intracavernous injection
      of nitric oxide can evoke a penile tumescence, which is similar to that of the
      neurostimulation. The results also suggest that the cholinergic nerves and the
      sinusoidal endothelium are involved in erection, and the effect of the former
      must depend on mediation of the latter. The study supports that cholinergic and
      nonadrenergic noncholinergic (NANC) neuroeffectors take part in penile erection,
      and nitric oxide may be one of chief NANC neurotransmitters.

PMID- 9594185
TI  - [Phospholipase A2 and multiple organ failure].

PMID- 9594186
TI  - [It is imperative to establish and improve the related rules and regulations of
      bone banks in China].

PMID- 9594187
TI  - [Effect of bone xenograft transplantation on total T lymphocyte and its subset
      counts in mouse blood and spleen].
AB  - Fresh calf cancellous bone xenograft (FX), antigen free cancellous bone carrier
      (BC) and reconstituted bone xenograft (RBX) were inplanted in the thigh muscle
      pouches of Balb/c mice. Histological examinations were done at 7, 14 and 28 days
      postoperation, and indirect immunofluorescence was used to determine the positive
      counts of Thy1, L3T4, Lyt2, and Tac T lymphocyte of the blood and spleen at the
      same time, with the normal mouse lymphocytes as control. There was no significant
      difference between the BC implanted group and the normal (control) group, while
      the FX group had a significant increase rates of Thy1, L3T4 and Lyt2, especially
      of Tac lymphocytes. The RBX implanted group had no increase of Tac but increase
      of Thy1 and Lyt2. Th-Ts ratio decreased, and it was probably caused by bovine
      bone morphogenetic protein (bBMP) in the RBX. Histologically, intense immune
      rejection was noted in FX implanted group but not in the other two groups.
      Heterotopic ossification was noted in the RBX implanted group. FX increased
      intense immunologic rejection in the host, bat RBX did not, that might be due to
      the decrease of Th/Ts caused by bBMP. Tac lymphocyte count may indicate the
      immunologic rejection of bone xenograft transplantation.

PMID- 9594188
TI  - [A comparative study of ethylene oxide and ionizing radiation for sterilizing
      bone grafts].
AB  - To find a good way for sterilization and disinfection of bone grafts, we compared
      the sterilization capacity of gaseous ethylene oxide (EO) and cobalt-60 gamma
      radiation. The bone chips were contaminated with 10(7) bacteria per milliliter of
      Staphylococcus aureus ATCC 25923, Bacillus subtilis globigii 8017 and Bacillus
      cereus 4001, then sterilized with various doses of gaseous EO or cobalt- 60 gamma
      radiation. The sterilization effect of EO was more stronger and faster than that
      of 60Co gamma radiation. The application of moderate doses of EO for sterilizing
      particulate bone grafts was recommended.

PMID- 9594189
TI  - [Immunological comparison of differently treated allografts of bone].
AB  - The immunnologic rejection induced by differently treated allografts of bone was
      compared. Methods Fresh bone (FB), autolyzed antigen-free bone (AAA), bone matrix
      gelatin (BMG), demineralized bone matrix (DBM) were implanted into the muscle
      pouch of mice, then, the immunological tests and alkaline phosphatase assay were
      conducted. Results Allogeneic FB induced the highest level of serum antibody in
      the host and stimulated lymphocytes proliferation remarkably in vitro; in
      contrast, AAA, BMG and DBM caused low titer of antibody and inhibited lymphocytes
      reproduction in vitro. Conclusions. Immunological rejection restrained
      osteogenesis of the bone implant, whereas the osteoinductive substance of bone
      suppressed immunological reaction.

PMID- 9594190
TI  - [Experience of banking osteoarticular and bone allografts].
AB  - Banking massive osteoarticular and other bone allografts were performed in our
      institute. For safeguarding recipients, the guidelines of donor selection were
      formulated and quality control was applied during procurement, preparation and
      storage of the grafts. Osteoarticular and bone grafts were harvested under
      aseptic or clean conditions, then, the bone and joint were cut into different
      shapes and sizes according to clinical needs, followed by removal of bone marrow
      and surface demineralization. In addition, sterilization with ethylene oxide or
      irradiation was carried out if necessary, at last the grafts were stored by
      freezing or freeze-drying. From October, 1991 to February, 1994, altogether 210
      osteoarticular and bone grafts were used in 20 hospitals across the country,
      among them 120 grafts were implanted into 84 patients in our hospital with short
      term satisfactory results.

PMID- 9594191
TI  - [Methods of the preparation of homologous bones and their effects of
      osteogenesis].

PMID- 9594193
TI  - [Serum tuftsin concentration as an indicator of postoperative splenic function
      after spleen-preserving surgery].
AB  - Serum tuftsin level was measured by reverse-phase high performance liquid
      chromatography in 40 cases. Compared with 10 normal controls, tuftsin level
      remained almost unchanged in 20 autotransplantation cases after splenic resection
      for traumatic rupture of the spleen, and in 10 partially splenectomy cases for
      splenomegaly hypersplenism. The level of tuftsin was lower than that of the
      normal controls though it was higher than that of total splenectomy cases.

PMID- 9594192
TI  - [Tuberculosis of the pancreatic head].
AB  - Eight patients with tuberculosis of the head of the pancreas were retrospectively
      reviewed. They were 4 men and 4 women (mean age 42.8 years). All patients
      complained of fever, sweating, fatigue, weight loss, and in the pain in the upper
      right belly. Abdominal mass was noted in 4 patients, jaundice in 3, and
      splenomegaly with hypersplenism in 4. Among the 8 patients, 5 suffered
      tuberculosis of the pancreas before the operation. All of them received
      laparotomy. Pancreatic tuberculosis in the all patients was confirmed by
      pathologically. Tuberculosis abscess was drained operatively. Antituberculosis
      therapy was available for all patients after the operation.

PMID- 9594194
TI  - [The therapeutic effect of somatostatin on acute severe pancreatitis: a clinical
      contrastive observation].
AB  - We observed the effect of somatostatin on the treatment of acute severe
      pancreatitis and on the inhibition of pancreatic secretion. 21 patients with
      acute severe pancreatitis were divided into control group (n = 12) and treatment
      group (n = 9) according to the admission time from 1992 to 1995. The control
      group was treated regularly and the treatment group was given intravenous
      somatostatin within 24h of onset 6mg/day for 5-7 days besides the regular
      treatment. No significant difference was noted in the general conditions of the
      two groups on admission. The volume of stomach suction in the somatostatin
      treated group was lower than that in the controls on the 2nd, 3rd and 4th
      admission days (P < 0.05). The serum amylase level of the treatment group was
      lower than that of the controls. 12 complications occurred in the somatostatin
      treated group as compared with 17 in the control group (P > 0.05). The clinical
      cure time was 15.6 +/- 4.8 days for the treatment group and 21.5 +/- 7.6 days for
      the controls (P = 0.02). We consider that as a pancreatic secretion inhibitor
      somatostatin can control the disease process and shorten the clinical cure time
      to some extent if it is used on the early stage of acute severe pancreatitis.

PMID- 9594195
TI  - [The path of gastric lymphatic drainage and its significance for redical
      resection of gastric carcinoma].
AB  - By dissecting 31 corpses' stomach and then thining the gastric lymphatic system
      with prussian blue staining, we found out that the gastric lymphatic return from
      the visceral surface to the parietal pleura mainly takes three ways: a lymphatic
      nodes of the coelica artery trunk, a lymphatic nodes beside the superior
      mesenteric artery, and lymphatic nodes beside the left inferior phrenic. The
      lympha of these paths flew to the parietal pleura around the left renal viens.
      This result can give reference to cleaning lymphatic nodes beside abdominal aorta
      during the radical operation of gastric carcinoma.

PMID- 9594196
TI  - [The angiographic classification and endovascular therapy of the vein of Galen
      aneurysmal malformation].
AB  - We treated 11 cases of the vein of Galen aneurysmal malformation, one of which
      was diagnosed by MRI only, and 10 underwent CAG diagnostic procedure. Among the
      10 CAG diagnosed cases, 5 were classified as the vein of Galen aneurysmal
      malformation (VGAM) with the AV shunt directing to the vein of Galen. The other 5
      were classified as the vein of Galen aneurysmal dilitation (VGAD) secondary to
      parenchymal AVM or dural AVF. 8 cases underwent endovascular treatment. For VGAM,
      the shunts in the wall of the vein were embolized. For VGAD, the primary AVM or
      AVF were embolized. The pathphysiology, angiographic characteristics,
      classification and the principle of endovascular therapy of the vein of Galen
      aneurysmal malformation were discussed.

PMID- 9594197
TI  - [The experience in applying bovine pericardial patch in the correction of
      tetralogy of Fallot].
AB  - From January 1982 to December 1994, 432 patients with tetralogy of Fallot
      underwent the corrective operation. We extended the right ventricular outflow
      tract (RVOT) in 271 of the patients by using bovine pericardial patch treated by
      glutaraldehyde. The results were satisfactory. We emphasize that bovine
      pericardial patch is good material for extending RVOT, because it has many merits
      including high intensity, satisfied suture, no leakage, and abundant supply. Long
      term follow up (maximum 12 years and 3 months) showed no ventricular aneurysm due
      to the degeneration of bovine pericardial patch.

PMID- 9594198
TI  - [24 patients with aneurysm of membranous ventricular septumi: clinical analysis].
AB  - 24 patients with aneurysm of the membranous ventricular septum were confirmed by
      operatively in our hospital. Four patients had true aneurysm of the membranous
      ventricular septum, and 20 false. According to the difference of membranous
      aneurysm (true or false) and the size of the defect, different methods of the
      operation were adopted. Postoperation intracardiac residual shunt was avoided.
      There was no death in the group. Follow-up for 9 years to 6 months showed
      excellent long-term results. The authors consider that the diagnosis of this
      disease before operation is difficult.

PMID- 9594199
TI  - [Autotransfusion of shed mediastinal blood after open heart operation].
AB  - This prospective study was designed to determine whether the autotransfusion of
      shed mediastinal blood (ATS) after open heart surgery is safe and effective.
      Forty-two patients undergoing cardiac operation were randomized to receive either
      nonwashed shed mediastinal blood (group 1; n = 22) or banked blood (group 2: n =
      20). No difference in mean age (group 1: 49 +/- 11 years; group 2: 45 +/- 12
      years), coronary artery bypass grafting (group 1: n = 5, 23%; group 2: n = 6,
      30%), valve replacement (group 1: n = 17, 77%, group 2: n = 14, 70%), and mean
      preoperative hemoglobin level (group 1: 13.7 +/- 2.3, group 2: 14.4 +/- 1.6) was
      noted between non-ATS and ATS groups (p = not significant). The mean hemoglobin
      levels after operation were similar in the two groups (group 1: 11.89 +/- 1.52;
      group 2: 12.03 +/- 1.34). No difference in the mean blood loss 4, 6 and 24 hours
      after operation (group 1: 33 +/- 190, 420 +/- 340 and 550 +/- 300; group 2: 340
      +/- 230, 420 +/- 280 and 670 +/- 380) was observed between the two groups. The
      mean volume autotransfused in group I was 380 +/- 230 ml (200 approximately 1300
      ml). In group I, the patients required bank blood 1080 +/- 720, compared with
      1780 +/- 1045 in group II. The bank blood requirement in group I reducted by 40%.
      These data demonstrate that ATS after open heart surgery is safe and effective.

PMID- 9594200
TI  - [A review of 10 patients of nephrectomy through laparoscope video].
AB  - Ten patients were subjected to nephrectomy through laparoscope video. Compared
      with routine nephrectomy, it has such merits as slight trauma, less bleeding and
      pain during the operation as well as quick recovery and short hospitalization. In
      6 male patients and 4 female patients the oldest one was 75 years old, and the
      youngest one was 15 years old. Seven patients suffered from nephrohydrosis and 3
      from polycystic kidney. Before the operation, the patients were found the loss of
      function of the diseased kidney. The video scope was inserted into the abdominal
      cavity through an operating hole under the navel making the exploration in the
      cavity; the other operations are as basical as routine operations. The ill kidney
      was cut off and put into a special pocket, then it was cut into pieces, and taken
      out. The abdominal membrane was enclosed by the emanometer, the drainage tube
      kept. In the 10 patients the operations were successful and satisfactory.

PMID- 9594201
TI  - [Female idiopathic urethra tumor: clinical features diagnosis and treatment].
AB  - Female idiopathic urethra tumors are reported rarely. We treated fourteen
      patients patients, and described the clinical manifestations and local features
      of the tumors, urethra liomyoma, and fibropolypus. We found that there are close
      relations among tumor stage, prognosis and pathological classification. The main
      diagnostic methods include vaginal touch, urethroscopy, B-ultrasound exam and
      biopsy. The diagnostic procedure recommended is tumor location-quality-stage or a
      three-step method. The main treatment is operation, however, the operative mode
      should depend on tumor stage and patient's life quality after operation.

PMID- 9594202
TI  - [The diagnosis and treatment of blunt renal trauma].
AB  - 225 patient with blunt renal trauma were treated from 1955 to 1994. Coexistent
      injuries of other organs were noted in 79 patients (35.11%). The extent of renal
      trauma was not demonstrated by hematuria. B-ultrasonography seemed to be best for
      the diagnosis of renal trauma. Abdominal incision was helpful to explore injuries
      of other organs and manage renal trauma. Early treatment of renal trauma was
      necessary for the treatment of shock and prevention of serious complication.

PMID- 9594203
TI  - [Transurethral noncontact laser ablation of the large prostate].
AB  - 42 cases of the large benign hypertrophy of the prostate were treated by
      transurethral noncontact laser ablation. The results of the patients followed up
      no less than six months and treatment were reported. The technique of the
      procedure and its related problems were described and our experience was
      presented. If we use the technique of the procedure skill fully, noncontact laser
      ablation of large benign hypertrophy of the prostate is safe and effective.

PMID- 9594204
TI  - Opportunities and potential treatment in renal diseases: from research to
      bedside.

PMID- 9594205
TI  - The prognosis of biopsy-proven lupus nephritis in chinese patients: long term
      follow-up of 86 cases.
AB  - OBJECTIVE: To investigate the prognosis of lupus nephritis (LN) and its
      influencing factors in patients with lupus nephritis in China. METHODS: A
      retrospective study was carried out in 86 patients followed up for at least 5
      years. Clinical features, serological and immunological tests were investigated.
      Renal biopsies were performed at the beginning of the study and repeated in some
      cases during the follow-up period. All the 86 patients had serum creatinine (Scr)
      level less than 132.6 mumol/L at the initial presentation and were divided into
      three groups according to the level of Scr at the end of the study. Group I: the
      patients with normal renal function (Scr < 132.6 mumol/L); Group II: the patients
      with mild-moderate renal insufficiency (132.6 mumol/L < or = SCR < or = 530.4
      mumol/L); Group III: the patients with end stage renal failure (ESRF) (Scr > or =
      530.4 mumol/L). RESULTS: Forty-seven patients reached clinical remission with
      normal renal function, 11 had with stabilization of renal function, although the
      systemic lupus erythematosis (SLE) activity relapsed repeatedly, while 28
      subjects developed renal insufficiency after 60-170 (mean 88.12 +/- 28.23) months
      of observation. ESRF rate was 11.6% in this group of patients. Eight patients
      died (2 died of infections and 6 died of ESRF) during the follow-up period. At
      the beginning of the study the rates of hypertension, persistent anemia and
      hematuria in Group II were 50%, 70%, and 70% respectively, being much higher than
      those in Group I. The calculation of AI and CI in 60 patients revealed that there
      were 65% of patients with AI > or = 7 and 70% of patients with CI > or = 3 in
      Groups II and III, while in Group I there were only 32% of patients with AI > or
      = 7 and 19% of patients with CI > or = 3. Sixteen cases had pathologic class
      changed in 48 repeated biopsies. Seven cases changed to Class IV, 5 to Class II,
      3 to Class V from other classes and one to class III from Class II. CONCLUSIONS:
      Factors associated with the development of renal insufficiency in these lupus
      patients included hypertension, anemia and hematuria. Renal biopsy evaluation
      offered additional prognostic information and showed that patients with severe
      active and chronic histologic changes were at risk for developing renal
      insufficiency. During the clinical course, the renal classification of LN changed
      in certain patients, thus the histologic classification of renal morphology at
      initial presentation did not fully predict the outcome. Renal involvement is very
      common in systemic lupus erythematosis (SLE) patients. Lupus nephritis (LN) is
      the most common form of secondary renal disease in China. It has various and
      unpredictable clinical features. The risks associated with its treatment have
      challenged investigators to detect the factors which may influence the survival
      rate of patients with LN and to develop the rational approaches to therapy.
      Decades of intensive investigation at many centers around the world had
      underscored the predictive value of demographic, clinical and laboratory data
      prior to treatment. Controversies still existed due to the difference in
      environment, race and the selection criteria of patients as well as the method
      used to evaluate the outcome. There are still some factors which are thought to
      have an impact on the prognosis of LN. Most of the articles on the prognosis of
      patients with LN were reported from Europe and America either about Caucasian or
      African-American patients. The prognosis of LN and its influence in Chinese
      patients need more elucidation.

PMID- 9594206
TI  - The study of IL-1 beta, TNF-alpha, IL-6 gene expression and plasma levels on
      hemodialysis before and after dialyzer reuse.
AB  - OBJECTIVE: To investigate the biocompatibility of dialyzer reuse. METHODS: Twenty
      two hemodialysis patients were randomized into cuprophan (CU, 7),
      polymethylmethacrylate (PMMA, 7) and polysulphone (PS, 8) membrane groups to
      observe IL-1 beta, TNF-alpha, IL-6 gene expression and their plasma levels by
      using themselves as control with enzyme-linked immunosorbent assay (ELISA),
      reverse transcription-polymerase chain reaction (RT-PCR) and in situ
      hybridization. RESULTS: Plasma levels of interlukin-1 beta (IL-1 beta), tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) were 14.07 +/- 3.32
      pg/ml, 67.41 +/- 19.79 pg/ml, 83.67 +/- 40.34 pg/ml; 12.80 +/- 3.01 pg/ml, 49.65
      +/- 9.75 pg/ml, 33.36 +/- 12.14 pg/ml and 14.41 +/- 3.16 pg/ml, 80.56 +/- 23.22
      pg/ml, 48.14 +/- 16.01 pg/ml, respectively, after patients dialyzed with CU, PMMA
      and PS membranes. Plasma cytokine levels decreased after reuse compared with
      those before reuse in each group. But no significant difference was found between
      them (P > 0.05); the levels of IL-1 beta, TNF-alpha, IL-6 gene expression after
      reuse were 5.61 +/- 0.33, 2.11 +/- 0.12, 5.04 +/- 0.19%; 2.43 +/- 0.19, 1.29 +/-
      0.11, 3.48 +/- 0.20% and 2.48 +/- 0.20, 1.24 +/- 0.11, 3.22 +/- 0.20%
      respectively by in situ hybridization, and 0.92 +/- 0.07, 0.63 +/- 0.05, 0.53 +/-
      0.05; 0.61 +/- 0.06, 0.47 +/- 0.04, 0.37 +/- 0.03 and 0.59 +/- 0.05, 0.44 +/-
      0.04, 0.38 +/- 0.03 by RT-PCR, respectively. After reuse there was significant
      decrease as compared with that before reuse (P < 0.001, P < 0.005 and P < 0.05,
      respectively). CONCLUSIONS: This suggested reprocessing dialyzer with
      formaldehyde reduced cytokine release and gene expression in peripheral blood
      mononuclear cells and enhanced dialyzer biocompatibility. It would be beneficial
      to reduce the dialysis cost and may reduce the complication related to a long
      term hemodialysis.

PMID- 9594207
TI  - Significance of P-selectin expression in human glomerulonephritis.
AB  - OBJECTIVE: To examine the relationship between P-selectin expression and human
      glomerulonephritis. METHODS: P-selectin expression was investigated in renal
      biopsies of glomerulonephritis patients (n = 133) by immunohistochemical and in
      situ hybridization analyses. They were divided into three groups based on the
      degrees of cells proliferation or sclerosis. Group I: histological lesions in
      glomeruli are mild (n = 23); Group II: glomerular cells proliferation is
      prominent (n = 91); Group III: glomerular sclerosis is severe (n = 19). The
      Kruskal-Wallis test, Chisquare test and Spearman's correlation were used in our
      study. RESULTS: In normal controls, renal P-selectin expression was negative (n =
      10). In glomerulonephritis, the up-regulated P-selectin expression on tubular
      epithelium was significantly higher than that on glomeruli and interstitium (P <
      0.01). P-selectin was expressed predominantly on platelets in glomeruli, and
      glomerular P-selectin expression was more significantly up-regulated in Group II
      than in Group I or Group III (P < 0.05; and P < 0.01, respectively). There were
      strong correlations between the degree of tubulointerstitial lesions and the
      expression of P-selectin on tubular epithelium or within interstitium (rs = 0.395
      and rs = 0.337, P < 0.01). Furthermore, P-selectin messenger RNA (mRNA) signals
      were also detected in the cytoplasm of glomerulus, tubular epithelial cells,
      interstitium and vascular endothelium. CONCLUSIONS: P-selectin might mediate
      intraglomerular platelets aggregation, activation and leukocyte accumulation in
      the early stages of human proliferative glomerulonephritis. The up-regulation of
      P-selectin in interstitium was associated with interstitial fibrosis and tubular
      atrophy and may contribute to the progression of glomerulonephritis.

PMID- 9594208
TI  - Existence of an abnormal nitric oxide metabolism seen in glomeruli and inner
      medullary collecting duct in diabetic rat.
AB  - OBJECTIVE: To investigate the nitric oxide (NO)-dependent 3', 5'-cyclic guanosine
      monophosphate (cGMP) stimulation or inhibition in isolated glomeruli and inner
      medullary collecting duct (IMCD) cells from normal and diabetic rats for
      elucidating the probable role of NO in diabetic nephropathy. METHODS: Glomeruli
      and IMCD cells were obtained from anesthetized diabetic rats, 2 weeks after
      streptozotocin-induction, and normal rats, and incubated for 10 minutes under
      basal state or adding different drugs. cGMP was measured by radioimmunoassay.
      RESULTS: Diabetic glomeruli had a higher generation of cGMP under basal state but
      failed to further response of L-arginine, which was contrary to the glomeruli
      from normal rats. NG-monomethyl-L-arginine prevented the elevation of cGMP after
      L-arginine stimulation in normal rats but not in diabetic rats. Acetylcholine
      produced a concentration-dependent of cGMP accumulation in the glomeruli of both
      groups, but the extent was relatively smaller in diabetic than in normal. A
      similar tendency was also observed in sodium nitroprusside treated glomeruli.
      However the cGMP increment in response to atrial natriuretic peptide was
      identical in the two groups. For the IMCD cells, neither the difference of basal
      cGMP nor those responses related to acetylcholine or sodium nitroprusside could
      be observed. But the attenuated response to L-arginine also existed in diabetic
      IMCD cells. CONCLUSION: Both diabetic glomeruli and IMCD cells have an abnormal
      NO metabolism, which may account in part for the disturbance of renal
      hemodynamics.

PMID- 9594209
TI  - Hemofiltration or hemodiafiltration with on-line production of substitution
      fluid: clinical observation of safety and effectiveness.
AB  - OBJECTIVE: To observe the safety and cardiovascular stability of on-line
      hemofiltration (HF) or hemodiafiltration (HDF) and evaluate the clinical
      effectiveness of one HF or HDF session in addition to two hemodialysis (HD)
      sessions weekly. METHODS: Forty patients were randomly divided into four groups:
      group predilutional (PRD) HF (filtration rate: 259-333 ml/min) group
      predilutional HDF (filtration rate: 167 ml/min) group postdilutional (POD) HDF
      (filtration rate: 83 ml/min) and group bicarbonate HD. The reduction rate of
      parathyroid hormone (PTH), beta 2-microglobulin (beta 2MG), alpha 1-microglobulin
      (alpha 1MG) and KT/V in the initial treatment of every month was observed, and
      the incidence of hypotension and pyretic reaction during each treatment was
      evaluated. RESULTS: After 4-month observation, the KT/V for Group POD HDF is
      better than that for the other three groups, and for Group PRD HDF is better than
      that for Group HF and HD. Serum level of PTH and beta 2MG was not decreased after
      every treatment in Group HD, and so was serum level of alpha 1MG in all groups.
      Significant removal of PTH and beta 2MG was observed in Group HF, PRD HDF and POD
      HDF. The monthly serum level of beta 2MG and KT/V were stable in all groups, but
      the monthly serum level of PTH tended to be decreased in Group HF, PRD, HDF, and
      POD HDF. The incidence of pyretic reaction in HF or HDF was the same as in HD.
      Although the ultrafiltration volume was significantly higher during HF or PRD HDF
      than during HD, the incidence of hypotension in HF or PRD HDF was similar to that
      in HD. CONCLUSIONS: On-line HF or HDF proved to be a safe and reliable method.
      POD HDF mode seems to have the best KT/V, HF or PRD HDF offers a better choice
      for preventing intradialytic hypotension. One HF or HDF session in addition to
      two HD sessions weekly is similarly effective to decrease the serum level of PTH
      and the proof of the clinical effectiveness of such a therapy awaits a long-term
      observation.

PMID- 9594210
TI  - Association of angiotensin-converting enzyme gene insertion/deletion polymorphism
      with the clinico-pathological manifestations in immunoglobulin A nephropathy
      patients.
AB  - OBJECTIVE: To investigate the relationship between angiotensin-converting enzyme
      (ACE) gene insertion/deletion polymorphism and the clinico-pathological
      manifestations in patients with immunoglobulin nephropathy (IgAN). METHODS: A
      flanking primer pair and an insertion-specific primer pair were used to perform
      two polymerase chain reactions so as to analyse the insertion/deletion
      polymorphism of ACE gene. RESULTS: There was a significantly higher genotype
      frequency for DD genotype in IgAN patients. The frequencies for DD genotype were
      also higher in those patients with hypertension and/or heavy proteinuria and/or
      severe glomerular sclerosis (P < 0.05). CONCLUSIONS: We observed a significant
      association of the deletion polymorphism of ACE gene with renal insufficiency,
      hypertension and severe glomerular lesions at biopsy. The deletion allele may
      play a role, at least to some extent, in the deterioration and progression in IgA
      nephropathy.

PMID- 9594211
TI  - Research on the mechanism of endothelin inflammatory effects on human mesangial
      cells.
AB  - OBJECTIVE: To investigate the mechanism of endothelin (ET) inflammatory effects
      on human mesangial cells (HMC). METHODS: The following experiments were performed
      on cultured HMC after ET-1 stimulation: (1) the expression of tumor necrosis
      factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), intercellular adhesion
      molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1
      (ET-1) itself messenger ribonucleic acid (mRNA) was determined by Northern Blot
      analysis; (2) the TNF alpha concentration was tested with radioimmunoassay; the
      IL-1 activity was assayed by the enhancement of thymocyte proliferation in
      response to mitogen; the surface expression of ICAM-1 and VCAM-1 was measured
      with cell enzyme linked immunoadsorbent assay (ELISA) analysis. RESULTS: ET-1
      (10(-7) mol/L) induced the following changes on HMC: (1) up-regulation of the
      expression of TNF alpha mRNA and protein; (2) up-regulation of the expression of
      ICAM-1 and VCAM-1 mRNA and protein; (3) up-regulation of the expression of ET-1
      itself mRNA. However, the expression of IL-1 mRNA and protein was not changed.
      CONCLUSIONS: ET-1 can stimulate HMC to produce TNF alpha, ICAM-1 and VCAM-1, and
      thereby induce inflammatory effects. ET-1 can also stimulate HMC to up-regulate
      the expression of ET-1 itself, so as to amplify inflammatory effects. So, ET-1 is
      actually an inflammatory mediator and may play an important role in the
      pathogenesis of glomerulonephritis.

PMID- 9594212
TI  - Inhibition of apoptosis by ginsenoside Rg1 in cultured cortical neurons.
AB  - OBJECTIVE: To examine the action of ginsenoside Rg1 on the prevention of
      apoptosis in cultured cortical neurons. METHODS Serum-deprivation was used as a
      model of apoptosis in cultured cortical neurons. Trypan blue exclusion test was
      set to examine cell viability. Lactate dehydrogenase release assay was used to
      investigate neuron injury. Two tests were performed for identification of
      apoptosis: fluorescence microscopy of cells stained with Hoechst 33 342 and
      Propidium Iodide; deoxyribonucleic acid (DNA) electrophoresis on agarose gel.
      RESULTS: Rg1 increased the neuron viability, lessened the release of LDH, reduced
      the morphological changes of nuclei, and decreased the cleavage of DNA.
      CONCLUSIONS: Rg1 can inhibit apoptosis of cultured cortical neurons induced by
      serum withdrawal. This action of Rg1 is concentration-dependent. The finding may
      give a clue to elucidate the antiaging activity of Rg1.

PMID- 9594213
TI  - Nitinol alloy endotracheal stent for treatment of tracheal stenosis.
AB  - OBJECTIVE: To treat inoperable tracheal stenosis by using nitinol endotracheal
      stent and to solve some problems facing endotracheal stenting with other kinds of
      stents. METHODS: The stent was made of nitinol wire. It can be deformed to
      smaller size in iced water. With a self-made introducer, the stent was placed in
      the location of stenosis. After hot water was injected into the introducer, the
      stent resumed its original form and anchored there itself. RESULTS: Altogether, 5
      patients with severe tracheal stenosis received this treatment. Dyspnea was
      relieved immediately after implantation of stents in all patients. Long-term
      follow-up also showed satisfactory results. CONCLUSION: Nitinol stent has some
      remarkable advantages as compared with other tracheal stents. It can be used as a
      new endoprosthesis in treating narrowed trachea.

PMID- 9594215
TI  - Genetic changes in nasopharyngeal carcinoma.

PMID- 9594214
TI  - Screening and identification of down-regulated genes in colorectal carcinoma by
      subtractive hybridization: a method to identify putative tumor suppressor genes.
AB  - OBJECTIVE: To search for new putative tumor suppressor genes in colorectal
      carcinoma. METHODS: Subtractive hybridization technologies were applied to screen
      and select genes, the expression of which was down-regulated in colorectal
      carcinoma. mRNAs uniquely expressed in normal cells but not in colorectal
      carcinoma were recovered as cDNA (sub-cDNA) after two rounds of subtractive
      hybridization with mRNA prepared from colorectal carcinoma. The sub-cDNAs were
      then used as probes to screen a normal human colon cDNA library constructed in
      lambda-Zap II phage. The DNAs of positive clones were in vivo excised, and
      partial DNA sequences were analyzed and compared with DNA sequence database
      Genbank. RESULTS: A total of 46 different clones with an average of about 1
      kilobases in transcript size was recovered. Among these 46 down-regulated genes
      in colorectal carcinoma were genes encoding immunoglobulin (n = 32), 40-kDa
      keratin intermediate filamentous protein or IFP (n = 1), major histocompatibility
      complex-related protein (n = 1), unrelated structural proteins (n = 10) and gene
      products yet to be identified (n = 2). RNA dotblot hybridizations confirmed that
      all 46 clones contained genes that were down-regulated and have not been reported
      before in colorectal carcinoma. CONCLUSION: The results of this study suggested
      that the 46 clones were down-regulated in colorectal carcinoma, they should be
      further studied as new putative tumor suppressor genes and could be used as new
      tumor markers of colorectal carcinoma.

PMID- 9594216
TI  - Emerging pathogens: the Hong Kong experience.

PMID- 9594217
TI  - A review on the operative techniques in liver resection.

PMID- 9594218
TI  - Circle of Willis: evaluation by computed tomography angiography with different
      concentration of contrast media.

PMID- 9594219
TI  - Penoscrotal area resurfacing with the scrotal myofasciocutaneous flap.

PMID- 9594220
TI  - Progress of clinical oncology in Asia.

PMID- 9594221
TI  - Three decades' experience in surgery of hepatocellular carcinoma.

PMID- 9594222
TI  - Relationship of p53 alteration and myc family gene overexpression with the
      clinical characteristics of lung cancer.
AB  - OBJECTIVE: To evaluate the relationship of p53 alteration and myc family gene
      overexpression with the clinical characteristics of lung cancer. METHODS: A
      series of 59 resected primary lung cancer specimens was analyzed for p53 gene by
      DNA/PCR sequencing and immunohistochemistry technique, and for myc family genes
      by RT-PCR methods. RESULTS: Thirty-seven of 57 tumors were found to have p53
      mutations or/and p53 protein accumulation. The presence of p53 alteration was not
      related to tumor size, lymph node metastasis, stage and relapse. Forty-seven
      cases were analyzed for myc family genes. The results showed that there was a
      positive correlation between unregulative expression of myc genes and the above
      mentioned clinical parameters. Our finding also showed that 19 of 30 cases (63%)
      with p53 alteration had myc gene overexpression which occurred in 63% and 76%
      cases with stage III and relapse, respectively, which was higher than 27% and 22%
      with p53 alteration but no myc gene overexpression and 50% and 71% with p53
      negative but myc gene overexpression. CONCLUSIONS: p53 alteration is a vital
      genetic event in the earlier stage of lung carcinogenesis, but not a prognostic
      marker. myc family genes overexpression may be regarded as one of the independent
      prognostic determinants in lung cancer. The cooperation between p53 alteration
      and myc gene overexpression may occur during progression of lung cancer, but
      prognostic determinant is myc gene overexpression.

PMID- 9594223
TI  - Surgical treatment of five hundred and thirty patients with early stage I and II
      stage cervical carcinoma.
AB  - OBJECTIVE: To investigate some problems in relation to the prognosis of surgical
      treatment of cervical carcinoma through analysing the clinical data of 530
      patients. METHODS: Five hundred and thirty patients with stage I or II cervical
      carcinoma received surgical treatment between 1966 and 1988. There were 66, 288,
      95 and 81 cases of stage IA, IB, IIA and IIB respectively. All patients underwent
      extensive abdominal hysterectomy and bilateral pelvic lymphadenectomy. The
      metastatic lesions of periaortic nodes in 18 cases were resected. Three methods
      of isolating ureter were used. The lymphangiography and dyeing of lymphaden was
      performed on 94 patients. RESULTS: The five-year survival rate was shown to be
      correlated with the pathologic type, cytologic grade, clinical stage and nodal
      metastasis of cervical carcinoma. The five-year survivals in stage IA, IB, IIA
      and IIB were 95.5%, 93.4%, 90.5% and 77.8% respectively; in squamous carcinoma
      and adenocarcinoma, 91.5% and 78.1% respectively; in the group with nodal
      spreading and the group without nodal spreading, 70.2% and 94.6% respectively; in
      patients of stage IIB treated by the method of isolating ureter outside ureter,
      83.1%; and in the group of lymphangiography and dyeing and the group not treated
      by lymphangiography and dyeing, 84.6% and 63.8% respectively. CONCLUSIONS: The
      method of isolating ureter outside ureter has an applying value for stage IIB
      cervical carcinoma. Lymphangiography and dyeing of lymphaden plays a role in
      raising the rate of nodal dissection.

PMID- 9594224
TI  - Vaccination with monoclonal anti-idiotypic antibody on immunocompetent mice
      bearing human ovarian carcinoma.
AB  - OBJECTIVE: To observe the effects of anti-idiotypic monoclonal antibody 6B11
      against ovarian carcinoma SKOV3 on immunocompetent mice BCF1 both in vivo and in
      vitro, so as to investigate the possibility of using it as a tumor vaccine.
      METHODS: After immunization with 6B11 and normal mice (NM) IgG respectively on 2
      groups of BCF1, blood, lymphocytes and tumor tissues were taken every other day.
      Ab3 was tested from blood samples. Subpopulations of lymphocytes were examined by
      FCM. The lymphocytes from immunized BCF1 were also cultured with SKOV3 to observe
      the chemotaxis and killing effects. Serial tissue sections were taken from BCF1
      after immunization by SRCA implantation of SKOV3. TIL and visible cancer cells
      were examined carefully and compared with those in the controls. RESULTS: Ab3
      rose quickly after immunization with 6B11 but lowered down gradually till the 9th
      week. The CD4+/ CD8+ ratio of BCF1 changed markedly after immunization with 6B11.
      The immunized lymphocytes showed a beautiful chemotaxis with and killing effect
      on SKOV3. During in vivo examinations, TIL were found significantly earlier in
      the immunized BCF1 than in the controls and reached the peak earlier in the
      former (on the 6th day) than in the latter, while the viability of tumor cells
      was vice versa between the two groups. CONCLUSION: 6B11 may be used as a vaccine
      for not only active immunization but also prevention of ovarian carcinoma.

PMID- 9594226
TI  - Long-term prognosis of percutaneous transluminal coronary angioplasty in 229
      cases.
AB  - OBJECTIVE: To evaluate long-term efficacy of percutaneous transluminal coronary
      angioplasty (PTCA) and the factors affecting its efficacy in Chinese patients.
      METHODS: Two hundred and twenty-nine patients who underwent successful PTCA in
      this institution were followed-up by direct interview or letters. The rate of
      follow-up was 95%. The period of follow-up were 0.5-8.4 (with mean of 2.3 +/- 1.8
      years). RESULTS: Angina Pectoris recurred in 76 (33.2%) of the patients. Cox
      regression analysis revealed that the relative risk of recurrence of angina
      pectoris was increased among the patients with triple vessel disease and with
      history of hypertension. During the period of follow-up, 2 (0.9%) patients died,
      6 (2.6%) had non-fatal acute myocardial infarction, 4 (1.7%) had coronary artery
      bypass graft surgery and 29 (12.7%) had repeat PTCA. The cardiac event-free
      survival rate calculated by Kaplan-Meier method was 84.8% at the first year and
      70.5% at the eighth year. Cox regression analysis revealed that there were
      positive correlation between the relative risks of cardiac events and stenosis of
      lesions before PTCA and residual stenosis of LAD after PTCA. CONCLUSION: The long
      term efficacy of PTCA in Chinese patients was good. The results of this study
      suggest that to decrease the residual stenosis of LAD during procedures could
      probably decrease the relative risk of cardiac events during follow-up.

PMID- 9594225
TI  - A study of apolipoprotein A-IV genetic polymorphism, serum lipids and
      lipoproteins in Beijing habitants.
AB  - OBJECTIVES: Apolipoprotein (apo) A-IV genetic polymorphism and its effect on
      serum lipids, apoA-I and apoA-IV were investigated in order to clarify the role
      of apoA-IV gene during the development of hyperlipidemia. METHODS: Four
      polymorphic sites (codon 127, 167, 347 and 360) of apoA-IV gene (exon 3) were
      determined in two groups of inhabitants in Beijing (Group I: 145 healthy
      individuals; Group II: 41 cases of hyperlipidemic patients and controls) by PCR
      RFLP technique. Serum concentrations of HDL-cholesterol (HDL-C), HDL3-C, HDL2-C,
      triglyceride (TG), total cholesterol (TC), apoA-I and apoA-IV were studied among
      the individuals with different genotypes of apoA-IV. RESULTS: In Group I,
      frequencies of the alleles were 0.648 and 0.352 in codon 127; 0.972 and 0.028 in
      codon 167; 0.817 and 0.183 in codon 347. Two common alleles were 0.941 and 0.059
      in codon 360. The results indicated that cases of codon 127 heterozygotes had a
      significantly higher serum TC level and cases of apoA-IV Ser127 homozygotes kept
      a markedly low TG level. Both homozygotes and heterozygotes which carried apoA-IV
      His 360 exhibited a significantly higher concentration of TC in comparing with
      that of apoA-IV Gln 360 homozygotes. The data from Group II showed that the
      allele frequency of His 360 had a significant difference between patients and
      controls. CONCLUSIONS: Certain polymorphic sites of apoA-IV gene might influence
      the serum lipid levels in both healthy persons and hyperlipidemic patients. His
      360 polymorphic position might have a relationship with the development of
      hyperlipidemia.

PMID- 9594227
TI  - Ultrastructural investigation of calcification and ossification in experimental
      fracture healing with special reference to osteogenic role of fibroblasts.
AB  - OBJECTIVE: To investigate ultrastructurally the process of calcification and
      ossification in experimental fracture healing. METHODS: A standardized fracture
      of the radius was made in rabbits. Undecalcified callus tissues from different
      fracture regions were subjected to ultrastructural observation under transmission
      electron microscope. RESULTS: In the mitochondria and membrane-bound vesicles of
      the fibroblasts, osteoblasts and chondrocytes, high electron density calcium
      granules were seen. These granules provided raw materials for the deposition of
      calcium salt crystals. Around these cells, round, oval or irregularly shaped
      matrix vesicles could also be discerned, and they became calcified and formed
      flocculent calcospherules. Then in the Type I collagen fibrils around the
      fibroblasts and osteoblasts, and in the Type II collagen fibrils around the
      chondrocytes, calcium salt crystals also appeared. Innumerable flocculent
      calcospherules and calcified collagen fibrils coalesced together, expanded and
      finally turned into pieces of bone tissues. The fibroblasts also possessed the
      indispensable prerequisites for calcification and ossification in fracture
      healing. They either transformed into osteocytes or degenerated, perished and
      eventually were replaced by bone tissues. CONCLUSIONS: Sequence of events taking
      place in calcification and ossification in experimental fracture healing was
      depicted. Calcification of matrix vesicles and collagen fibrils triggered these
      processes. Evidence of osteogenic role played by fibroblasts was provided.

PMID- 9594228
TI  - Comparison of tyrosine hydroxylase immunoreactivity in cochleas of chinchilla and
      guinea pig.
AB  - OBJECTIVE: To investigate the distribution of the tyrosine hydroxylase (TH)
      immunoreactivity in the cochleas of chinchilla and compare it with guinea pig.
      METHODS: Ten healthy chinchillas and six healthy guinea pigs were used in this
      study. The surface preparation of cochleas were obtained by microdissection. The
      TH-like immunoreactivity on the surface preparation as examined by the avidin and
      biotinylated horseradish peroxidase macromolecular complex (ABC) technique and
      investigated with light microscopy. RESULTS: TH-like immunoreactivity was seen in
      the region from modiolus to the habenula perforata. There are two different
      groups of fibers in this area, one is blood vessel dependent, the other is a
      blood vessel independent system. No TH-like immunoreactivity was present in the
      inner spiral bundle (ISB) and the tunnel spiral bundle (TSB) regions in
      chinchilla cochleas. TH-like immunoreactivity was found in the region from
      modiolus to the habenula perforata and the ISB and TSB regions in the organ of
      corti (OC) in guinea pig cochleas. CONCLUSIONS: The presence of TH
      immunoreactivity on the cochlea of chinchilla and guinea pig is different. TH
      like immunoreactivity on chinchilla cochlea was involved only in the fibers
      corresponding to the sympathetic fibers on cochlea of guinea pig. No fibers
      corresponding to the dopaminergic olivocochlear lateral efferent system of guinea
      pig were found in ISB and TSB within the OC in chinchilla.

PMID- 9594229
TI  - Microlamellar keratectomy for correction of high myopia.
AB  - OBJECTIVE: To evaluate the preliminary results of high myopia correction by
      microlamellar keratectomy (MLK). METHODS: Seventy-three eyes of 43 patients with
      high myopia were treated by MLK. The preoperative refraction ranged from -7.00D
      to -32.00D (mean -18.45D +/- 6.18D). All the operations were performed with the
      special apparatus for MLK. RESULTS: At 6 months after surgery, in the 73 eyes
      except 2 with new other symptoms, all the uncorrected visual acuity and corrected
      visual acuity were better than or equal to their preoperative ones respectively.
      Uncorrected visual acuity was better than or equal to the preoperative corrected
      visual acuity in 51 eyes (71.83%). No severe complications occurred during and
      after operation. The postoperative refractive status was stable. CONCLUSIONS: MLK
      is effective to reduce high myopia and has some special advantages as compared
      with radial keratotomy (RK), photorefractive keratectomy (PRK) and laser in-situ
      keratomileusis (LASIK). But influenced by several factors, the predictability of
      this procedure is merely fair. It is suggested that this kind of procedure must
      be done with excellent microsurgery equipments, microsurgical skills and much
      more clinical experience of managing corneal disorders.

PMID- 9594230
TI  - The evaluation of intra- and extra-cranial circulation in subclavian steal
      syndrome.
AB  - OBJECTIVE: To compare the efficacy of transcranial Doppler ultrasound (TCD) and
      digital subtraction angiography (DSA) in identifying the clinical and hemodynamic
      relationship between intra- and extra-cranial circulation and subclavian steal
      syndrome. METHODS: Sixteen patients were collected. The intra- and extra-cranial
      arteries were insonated with Doppler ultrasound. DSA and brain CT were performed
      in all patients. The relationship between the grade of arterial stenosis showing
      in DSA and the flow direction showing in TCD was studied. RESULTS: TCD showed
      reversal flow of the vertebrobasilar artery in 13 patients, normal flow in 3,
      which was influenced obviously by fist-clenching. In the hyperemia test, the flow
      velocity and the direction changed significantly in all patients. The steal
      phenomenon of the middle cerebral artery (MCA) was coincident with that of the
      arterial cerebral artery (ACA) in 2 cases. Stenosis of MCA or ACA was found in 5
      cases (31%). Nine patients were treated with arterial bypass or angioplasty. TCD
      was performed during the follow-up. CONCLUSIONS: Reversal flow of the vertebral
      artery may occur in rest or only in exercise, depending on the grade of
      subclavian arterial stenosis. Hyperemia test is the most sensitive index. It is
      necessary to monitor blood flow in the MCA and basilar artery in hyperemia test.
      The coexistence of intra- and extra-cranial arterial stenosis is common.

PMID- 9594231
TI  - Radiotherapy of carcinoma of oesophagus in China.

PMID- 9594232
TI  - UFT: biochemical modulation for 5-fluorouracil (5-FU).

PMID- 9594233
TI  - New anticancer drugs in Europe.

PMID- 9594234
TI  - Recent study on colorectal cancer in China: early detection and novel related
      gene.

PMID- 9594235
TI  - Regulation of rhTNF in abdominal cavity to the expression of C-erbB-2 of ovarian
      cancer nude mice ascites tumor.

PMID- 9594236
TI  - Successful cardiopulmonary resuscitation of a patient developed a 52-minute
      cardiopulmonary arrest secondary to acute myocardial infarction.

PMID- 9594237
TI  - Management of quinidine syncope in twenty cases.

PMID- 9594238
TI  - Medical education at the University of Hong Kong: changes and challenges.

PMID- 9594239
TI  - Good clinical practice in Hong Kong: impact of the new international guideline.

PMID- 9594240
TI  - Current views of direct angioplasty in acute myocardial infarct.
AB  - OBJECTIVE: The management strategies after acute myocardial infarction (AMI) have
      been evolving from simple supportive treatment to various protocols of
      thrombolytic therapies, and then to mechanical revascularization by balloon
      angioplasty in recent years. However, controversies still exist between which is
      the best treatment approach. METHODS: An extensive analysis was carried out in
      over 120 articles reported recently in the literature. RESULTS: Most reported
      series have shown that direct angioplasty is a feasible and safe option for the
      management of acute myocardial infarction. Large scale randomised studies
      comparing direct angioplasty versus thrombolytic therapy in acute myocardial
      infarction have also reported very favourable acute and long term outcomes by
      direct angioplasty as compared to thrombolytic therapy. The results are at least
      equivalent, if not better, by direct angioplasty. Acute results include better
      reperfusion rate of infarct related artery, less bleeding and stroke
      complications, shorter hospital stay, and most importantly, lower in-patient
      mortality (around 2% in direct PTCA group versus 6% in thrombolysis group) and
      less recurrent ischaemic event (around 10% in direct PTCA group versus 30% in
      thrombolysis group). Despite some delay in the commencement of treatment by
      direct angioplasty than thrombolytic therapy, the left ventricular function
      remains comparable in the two groups and the overall long term outcomes are very
      favourable with direct angioplasty. Specific indications for direct angioplasty
      include patients with cardiogenic shock after AMI and patients with
      contraindications to thrombolysis. No reflow phenomenon is still an issue of
      concern. It is in general contraindicated to use angioplasty after failure of
      thrombolysis. The cost implication is not far exceeding that of thrombolysis
      therapy. CONCLUSIONS: Direct angioplasty for acute myocardial infarction should
      be established as a treatment option if the circumstances allow. Planning should
      be carried out at the hospital and community level in order to make direct
      angioplasty a high priority treatment option for patients with acute myocardial
      infarction.

PMID- 9594241
TI  - Why is lung cancer common in non-smoking women in Hong Kong: from epidemiologic
      to molecular studies.

PMID- 9594242
TI  - Common endocrine and metabolic disorders among the Chinese in Hong Kong.

PMID- 9594243
TI  - Management of end-stage renal failure: a Hong Kong perspective.

PMID- 9594244
TI  - Current status of therapeutic endoscopy in hepatobiliary and pancreatic surgery.
AB  - As in any other facets of our medical practice, the successful management of
      patients with different hepato-biliary and pancreatic disease depends on the
      conjoint efforts of a well coordinated team of different disciplines. In addition
      of ERCP/ES, interventional radiology and laparoscopic surgery are becoming
      indispensable tools for surgeons and are providing us with new therapeutic
      options. Although the conventional territory of surgery is shrinking, the
      improved outcome of patients remains as the best testimony for our continuing
      support to the team approach. Hopefully, data from well conducted clinical
      studies which could help us to elucidate the best measure for our patients would
      be available from China and elsewhere.

PMID- 9594245
TI  - Assisted reproduction technology in Queen Mary Hospital: ten years' experience.
AB  - PURPOSE: To review the experience of an assisted reproduction program. DATA
      SOURCES: Department of Obstetrics and Gynaecology, University of Hong Kong. STUDY
      SELECTION: Assisted reproduction in a tertiary referral centre. DATA EXTRACTION:
      Results of assisted reproduction from 1986-1996. RESULTS: In the past ten years,
      1561 treatment cycles of in vitro fertilization and embryo transfer (IVF), 257 of
      gamete intrafallopian transfer (GIFT) and 217 of pronuclear stage tubal transfer
      (PROST) were initiated. The clinical pregnancy rates per cycle started were 10.8%
      for IVF, 16.3% for GIFT and 15.7% for PROST. As a result of improvement in
      ovarian stimulation and embryo culture, the success rate of the program increased
      in recent years. The pregnancy rate of IVF per embryo transfer was 20.2% in 1995.
      Embryo cryopreservation program was started in 1992. Since then, 664 cycles of
      replacement of frozen-thawed embryos were completed with a pregnancy rate of
      14.6% per cycle. One hundred and forty-three cycles of assisted fertilization
      using various techniques, namely partial zona dissection, subzonal sperm
      injection and intracytoplasmic sperm injection, were performed. The success rate
      was the highest for the latter technique with a pregnancy rate of 14% per
      transfer cycle. A prospective randomized control trial on the use of coculture in
      assisted reproduction had also been done. Results indicated that coculture of
      embryos with human oviductal cells improved the implantation rate of the embryos.
      CONCLUSION: Various technique development have been made to improve the success
      rate of assisted reproduction as well as the quality of treatment of infertility.

PMID- 9594246
TI  - Changing pattern of neonatal jaundice and kernicterus in Chinese neonates.

PMID- 9594247
TI  - Brain iron and neurological disorders.

PMID- 9594248
TI  - Pathology of esophageal cancers: local experience and current insights.
AB  - Esophageal cancer is very popular in Hong Kong. The tumor is often prevalent in
      males and has a modal peak of occurrence in the 7th decade. The pathogenesis of
      the esophageal neoplasm is still uncertain but likely to be multi-factorial. The
      commonest histological subtype is squamous cell carcinoma. Besides,
      mucoepidermoid carcinoma/adenosquamous carcinoma, adenocarcinoma, small cell
      carcinoma, sarcomatoid carcinoma, adenoid cystic carcinoma, undifferentiated
      carcinoma, melanoma and gastrointestinal autonomic nerve tumor are also found in
      a minority of patients. The proportion of various histologic subtypes is
      different from the Western populations. Concerning the genetic alternation, P53
      mutation is common in esophageal squamous cell carcinoma. Esophageal cancer has
      its unique pattern of P53 mutations in Hong Kong. In addition, intramural
      metastasis and multiple lesions are characteristic features in esophageal
      squamous cell carcinoma. Important pathologic factors in determining the
      prognosis of patients with esophageal cancer includes completeness of surgical
      resection, stages, tumor dimension as well as MIB-1 scores and the presence of
      P53 mutations.

PMID- 9594249
TI  - Frequency distributions of plasma apolipoprotein(a) levels and phenotypes: a
      comparison between southern and northern Chinese populations.
AB  - OBJECTIVE: This study was designed to examine the genetic variation and levels of
      apolipoprotein (a) [apo(a)] in Chinese living in two different geographical
      regions of China and the influence of the apo(a) size polymorphism on plasma
      apo(a) levels. METHODS: An immunoradiometric assay was used to determine plasma
      apo(a) levels and a simplified and sensitive SDS-agarose gel electrophoresis
      method followed by immunoblotting with chemiluminescent detection for apo(a)
      phenotyping was employed to compare the frequency distributions of apo(a) levels
      and phenotypes in southern (Hong Kong) and northern (Henan) Chinese populations.
      RESULTS: Distributions of plasma apo(a) levels were highly skewed in both
      population groups. Although plasma apo(a) levels were generally higher in
      northern Chinese than in southern Chinese this was not explained by differences
      in K-IV repeats allele frequencies between these two population groups. The
      association of K-IV repeat length with apo(a) levels is similar in the two
      populations. CONCLUSIONS: We conclude that besides the apo(a) size polymorphism,
      which is similar in these two Chinese populations, other factors affect apo(a)
      levels to a certain degree. Most likely, this is the sequence variation in apo(a)
      gene which may not be the same in different Chinese populations.

PMID- 9594250
TI  - Current status of breast cancer in Hong Kong.
AB  - OBJECTIVE: To study the mode of presentation, the tumor, nodes, metastasis (TNM)
      staging and the efficacy of multimodal treatment of breast cancer among Chinese
      women treated in Queen Mary Hospital. METHODS: The available records of all
      breast cancer patients treated between January 1980 and December 1994 were
      reviewed. The mode of presentation, the TNM staging of the disease, estrogen
      receptor status and the mode of surgical and adjuvant treatment were studied.
      Statistical correlation was performed between the factors studied and the
      survival time. RESULTS: Seven hundred and one cases of breast cancer were
      identified. The mean age of the patients was 56.6 years (range, 20-98 years). The
      most common complaint was the presence of a mass which occurred in 635 (90.6%)
      patients and 454 (71.5%) of these patients were painless. The majority of
      patients had T2 tumours (51.8%) and stage II disease (59.6%), but only 86 (12.3%)
      patients underwent breast conservative therapy (BCT). Estrogen receptor was
      positive in 43% of patients. Two hundred and ninety (41.4%) patients were node
      positive and the mean number of involved nodes was 3.8 per patient. Adjuvant
      chemotherapy was given to 125 node positive patients, adjuvant tamoxifen to 188
      patients and both to 63 patients. Univariate analyses of factors possibly
      affecting survival showed that advanced stage disease and nodal involvement were
      associated with a significantly lower survival time. Among the node positive
      patients, those with seven or more involved nodes had a shorter survival. The
      types of surgery and adjuvant treatment (for node positive patients) had no
      direct correlation with survival. CONCLUSION: Our results showed that the
      majority of our patients presented with a painless mass and the final outcome was
      determined by the tumour load at the time of presentation (TNM staging and nodal
      status).

PMID- 9594251
TI  - Pregnancies from subzonal insemination of unfertilized oocytes after conventional
      IVF.
AB  - OBJECTIVE: To evaluate the efficacy of subzonal insemination (SUZI) as applied to
      unfertilized oocytes after initial insemination. METHODS: Unfertilized oocytes at
      metaphase II obtained after conventional IVF from 14 patients were selected for
      reinsemination by SUZI. The fertilization rate and pregnancy outcome were
      assessed. RESULTS: Of the 57 unfertilized oocytes at metaphase II, 10 (17.5%)
      became fertilized after SUZI. Eight of the 10 (80%) oocytes showed normal
      fertilization with two pronuclei while the other two (20%) oocytes were
      polyspermic. Five (35.7%) of the 14 patients had embryo transfer resulting in two
      (14.3%) pregnancies. One patient had a spontaneous abortion and the other had a
      live birth at term. CONCLUSION: Reinsemination of unfertilized oocytes by SUZI
      could be of value when fertilization fails after initial insemination.

PMID- 9594252
TI  - Management of fulminant hepatic failure at Queen Mary Hospital.
AB  - OBJECTIVE: To evaluate the strategy of the management of patients with fulminant
      hepatic failure at Queen Mary Hospital. METHODS: In the period 1994 through 1996,
      30 patients with fulminant hepatic failure were managed by active supportive
      treatment in the Intensive Care Unit in preparation for liver transplantation.
      Liver transplantation was performed in 14 patients (aged 17-47), 3 of whom
      received liver grafts from brain-stem dead donors and 11 received live-related
      grafts from family members. The median duration from admission to liver
      transplantation was 3 days (range: 1-6 days). RESULTS: Thirteen patients (93%)
      survived the liver transplantation and are well after a median period of follow
      up of 7 months. The only mortality was in a patient with pre-exiting renal
      transplantation and hepatitis B infection, who died from intra-abdominal
      candidiasis. CONCLUSION: The strategy of active supportive treatment and early
      liver transplantation using live-related liver graft is probably the key to the
      success of the management of fulminant hepatic failure in our series.

PMID- 9594253
TI  - Comparison of whole body MRI and radioisotope bone scintigram for skeletal
      metastases detection.
AB  - OBJECTIVE: To compare whole body magnetic resonance imaging (MRI) using fast
      sequences with radioisotope bone scintigraphy (BS) for the detection of
      metastases in the entire skeleton. METHODS AND RESULTS: In forty-four patients
      suffering from carcinoma of lung, breast and prostate whole body MRI could
      generally be accomplished in about 39 minutes and it was shown to have a higher
      skeletal metastases detection compared with BS in the spine, pelvis, limb bones,
      sternum, scapula, and clavicle, but lower in the ribs and skull. CONCLUSIONS: We
      think for addressing the status of skeletal metastases only, bone scintigram is
      still preferred over whole body MRI. When bone scintigram is unavailable, whole
      body MRI is a practical and acceptable alternative especially when extra-osseous
      metastases are also of concern.

PMID- 9594254
TI  - Alpha and beta thalassemias in Hong Kong.

PMID- 9594255
TI  - Unrelated marrow donor registry for Chinese.

PMID- 9594256
TI  - Effects of antisense oligodeoxynucleotides to NR1 on suppression of seizures and
      protection of cortical neurons from excitotoxicity in vivo and in vitro.
AB  - OBJECTIVE: To investigate the effects of NR1 subunit on the initiation and
      development of seizures and protection of cortical neurons from excitotoxicity by
      using antisense oligodeoxynucleotides (ODN) to NR1 in vivo and in vitro. METHODS:
      Intracerebroventricular injection, temporal cortex slices discharge, cerebral
      cortical neuronal culture, induction of neurotoxicity and [3H]MK-801 binding were
      used in this study. RESULTS: After an antisense ODN for NR1 was administered
      intracerebroventricularly (i.c.v. 100 micrograms in 10 microliters) once daily,
      for three days in genetically epilepsy-prone rats (GEPR, P77PMC), the animals did
      not develop any clonic and tonic convulsions and their seizure scores were
      significantly lower compared to the control groups. The frequency and amplitude
      of early seizure-like events (SLEs) and late recurrent discharges (LRD), induced
      by lowering Mg2+, were reduced in entorhinal cortex (EC) of the temporal slice
      treated by antisense ODNs. Pretreatment with antisense ODN (2 microM) protected
      more than 52% of glutamate-sensitive neurons and reduced the [3H]MK-801 binding
      to 50% in cultured cerebral cortical neurons. CONCLUSIONS: N-methy-D-aspartate
      receptors (NMDAR), specifically the NR1 subunit, may participate and play
      important roles in the initiation and propagation of epilepsy in the P77PMC rat.

PMID- 9594257
TI  - Immunofluorescence study of type IV collagen alpha chains in epidermal basement
      membrane: application in diagnosis of X-linked Alport syndrome.
AB  - OBJECTIVE: To detect the distribution of alpha 5 (IV) chain of collagen on the
      glomerular basement membrane (GBM) and epidermal basement membrane (EBM) in the
      Chinese Alport syndrome (AS) kindreds and to develop a simple diagnostic
      alternative method to electronic microscopy for diagnosis of AS. METHODS: Four
      male patients from 4 unrelated families manifested with hematuria, sensorineural
      hearing loss and had distinct family history. All patients had the characteristic
      AS pathologic changes by electron microscopy on their renal biopsy tissues. Three
      normal skin samples and 2 normal kidney samples were used as normal controls.
      Monoclonal antibody-based IF test was performed to examine the alpha 5 (IV) NC1
      domain in EBM of normal controls, X-linked AS patients and their parents, and in
      GBM of normal controls and AS patients. RESULTS: In normal controls as well as
      the patients' fathers, all the monoclonal antibodies used in EBM and GBM staining
      showed positive reactions along basement membranes in a linear pattern.
      Characteristically, in AS patients there were negative reactions to monoclonal
      antibodies anti-alpha 5 (IV) NC1 domain in EBM and anti-alpha 3-5 (IV) NC1
      domains in GBM. In patients' mothers, alpha 5 (IV) chain was distributed
      segmentally in EBM. CONCLUSION: The staining of alpha 5 (IV) NC1 domain in EBM by
      IF can be used to diagnose patients and screen defect-gene carriers of X-linked
      AS.

PMID- 9594258
TI  - Paediatric upper gastrointestinal endoscopy: a 2-year review.
AB  - OBJECTIVE: To review the paediatric upper gastrointestinal endoscopy service in a
      paediatric department in Hong Kong. METHODS: Records of all endoscopies
      undertaken in this department from May 1995 to January 1996 were retrieved and
      analysed. RESULTS: The commonest indication for upper endoscopy was dyspepsia
      with 88% positive histological findings. Helicobacter pylori (H. pylori) was
      found in 25% of this group of children. CONCLUSION: Paediatric upper
      gastrointestinal endoscopy service is invaluable in a paediatric department by
      providing useful diagnostic information which would otherwise be missed.

PMID- 9594259
TI  - TGF-beta 3 inhibits the increased gene expressions of pulmonary surfactant
      proteins induced by dexamethasone in fetal rat lung in vitro.
AB  - OBJECTIVE: To determine the effects of transforming growth factor-beta 3 (TGF
      beta 3) on expressions of surfactant proteins (SPs). METHODS: Northern blot
      hybridization and reverse transcriptase polymerase chain reaction (RT-PCR) were
      employed to determine the SP-A, SP-B and SP-C mRNA levels of cultured lung
      explants and type II cells from fetal rat lungs. RESULTS: TGF-beta 3 alone did
      not affect the expressions of SPs either in explants or in type II cells.
      However, TGF-beta 3 did inhibit the increase of SP-B, SP-C mRNA levels caused by
      dexamethasone (100 nmol/L), in a dose-dependent manner. Furthermore, TGF-beta 3
      had no direct inhibition on the increase of SP-B, SP-C mRNA induced by
      dexamethasone in type II cells, but had an indirect inhibitory effect mediated by
      fibroblasts. CONCLUSION: TGF-beta 3 plays an important inhibitory role in the
      development of pulmonary surfactant proteins. The present study may provide a
      possible explanation for the unideal effect of glucocorticoids in the prevention
      of neonatal respiratory distress syndrome.

PMID- 9594260
TI  - Antiganglioside antibodies in cerebrospinal fluid of children with
      neuropsychiatric lupus erythematosus.
AB  - OBJECTIVE: To determine antiganglioside antibodies (AGA) in cerebrospinal fluid
      (CSF) of children with neuropsychiatric lupus erythematosus (NPLE), and to
      investigate their association with clinical manifestations and other laboratory
      tests. METHODS: An enzyme linked immunoabsorbent assay was used to detect AGA in
      22 CSF samples obtained from 18 children with systemic lupus erythematosus (SLE).
      These patients were further classified into clinical active NPLE (9 patients) and
      SLE (9 patients) groups. Indirect immunofluorescent assay was used for
      determination of CSF antinucleus antibodies (ANA). RESULTS: AGA could be found in
      CSF of all the 9 active NPLE children who had neuropsychiatric manifestations
      within 6 months before or after AGA was tested. A clear association was observed
      between AGA and brain CT scan. No detectable ANA was found in CSF samples even
      though high titer of ANA was present in corresponding serum samples of SLE
      patients. CONCLUSION: Detection of AGAs in CSF, more sensitive and specific than
      routine CSF examination and EEG, and positively associated with brain CT scan, is
      a simple and practical test for early judgment of childhood NPLE.

PMID- 9594262
TI  - Our young pediatricians are growing up.

PMID- 9594261
TI  - Changes in intracellular and extracellular calcium concentration of the
      myocardial cells during heart failure in children.
AB  - OBJECTIVE: To explore the relationship between heart failure and changes in
      intracellular calcium concentration of the myocardium. METHODS: The intra-and
      extracellular concentration of ionized calcium and total calcium of myocardium in
      11 cases of heart failure was measured using calcium fluorescence indicator Fura
      2 and atom absorption spectrophotometry. The activity of the erythrocyte membrane
      pump was determined with hemolysate chemical method. RESULTS: The concentration
      of ionized calcium in myocardial cells and the erythrocyte was significantly
      higher in the patients with heart failure (280.85 +/- 47.8 nmol/L, 1.76 +/- 0.04
      F335/F385) than in those without heart failure (121.88 +/- 13.15 nmol/L, 1.47 +/-
      0.08 F335/F385). Total calcium in the erythrocyte was also increased markedly in
      the patients with heart failure, but the activity of the erythrocyte membrane
      pump was lower than in those without heart failure. The intracellular calcium of
      the peripheral erythrocyte and the activity of membrane pump returned to normal
      after the heart failure was cured. CONCLUSION: There is excessive calcium
      accumulation in the myocardium and erythrocyte and the latter may be cause of the
      disturbance of myocardial diastolic function during heart failure.

PMID- 9594264
TI  - Analysis of clonality of lymphocytic leukemia and lymphoma by T-cell receptor
      gene rearrangement.
AB  - OBJECTIVE: To analyse the relationship between the number of T-cell receptor
      (TCR) gamma gene rearrangement and clonality of malignant cells in lymphocytic
      leukemia and lymphoma. METHODS: The TCR gamma gene characteristics of 73 cases of
      lymphocytic leukemia and lymphoma and other diseases that had presented 1 or 2
      prominent bands of amplified TCR gamma VI subgroups-J1/2 gene rearrangement (GR)
      were detected by polymerase chain reaction-restriction enzymes (PCR-RE),
      heteroduplex formation (HDF), DNA sequencing and single-strand conformational
      polymorphism (SSCP). RESULTS: Thirty-four percent patients had 2 of TCR gamma GR
      (biallelic rearrangement); twenty-six percent had 1 of TCR gamma GR; fifty-four
      percent of acute lymphocytic leukemia's and nineteen percent of non-Hodgkin's
      lymphomas (NHL) had 2 of TCR gamma GR. HDF could rapidly confirm more than 1 of
      alleles while more alleles were difficult to be recognized by restriction
      analysis. Sense and antisense strands of heteroduplex were composed of 2 of TCR
      gamma GR respectively. By combining HDF method, oligoclonalities in three
      patients (2 acute lympholytic leukemia and 1 myelodysplastil syndrome and clone
      evolution in one NHL were found. CONCLUSIONS: The fact that many patients had 2
      of TCR GR means that complications of two neoplastic clones can be affirmed only
      if more than 2 of TCR GR are found. HDF can be used to detect the clonality,
      oligoclonality and polyclonality of lymphoid cells in lymphocytic leukemia and
      lymphoma by analysis of the difference of gene segments. HDF is a reliable method
      for the clone evolution research of lymphoid malignancies in progression.

PMID- 9594263
TI  - Secondary prevention of cardiac events following myocardial infarction: effects
      of atenolol and enalapril. Beijing Collaborative Study Group.
AB  - OBJECTIVE: To investigate the actions of beta-blocker (atenolol) and ACE
      inhibitor (enalapril) for the secondary prevention of the main cardiac
      complications after acute myocardial infarction (AMI). METHODS: 1106 cases of AMI
      from 7 hospitals in the Beijing area were collected and were divided randomly
      into three groups: control (group C), atenolol (group A), and enalapril (group
      E). Drugs for investigation were administered 2-4 weeks after the onset of AMI,
      and the subjects were followed up for a median period of 19 months. All patients
      were given aspirin 50 mg/day. The end points of observation were cardiac events
      and non-cardiac events. Cardiac events included sudden cardiac death (SCD), heart
      failure death, total cardiac deaths, and myocardial re-infarction. RESULTS: The
      clinical conditions of the three groups were compatible. Sixty-six cardiac events
      (6.0%) occurred. Comparing with group C, the rate of SCD decreased significantly
      by 68% in group A after atenolol treatment for 28 months. Both atenolol and
      enalapril significantly increased left ventricular ejection fraction (LVEF),
      whereas in group C the LVEF did not change during the follow-up period. There was
      obvious decreasing tendency of the survival curve in group C, compared with the
      other two groups. Totally drugs decrease one cardiac death 0/00/month. But the
      rate of myocardial re-infarction was the same in the three groups. No serious
      side effects on blood pressure or heart rate were observed. CONCLUSIONS: Both
      atenolol and enalapril (domestic products) are beneficial to the secondary
      prevention of SCD and heart failure death after AMI, but not to re-infarction.
      Both drugs should be continued for a prolonged period to be effective. Drugs
      given 2-4 weeks after acute stage are also effective, with no serious side
      effects.

PMID- 9594265
TI  - Surgical treatment for primary hyperparathyroidism.
AB  - OBJECTIVE: To document the recent surgical results in the treatment of primary
      hyperparathyroidism (HPT) at Queen Mary Hospital. METHODS: From 1995 to 1996, 30
      patients underwent 31 operations for primary HPT. The data of 11 men and 19 women
      with ages ranging from 19 to 86 years (median: 57 years) were prospectively
      recorded with emphasis on the need of preoperative localization. RESULTS:
      Symptoms of hypercalcemia were present in 20 (67%) and complications in 17 (57%)
      patients, respectively. Seventy-seven localization studies were performed in 28
      patients (average: 2.6 tests/patient). Localization was accurate in 12 of 23
      (52%) ultrasonographies, 11 of 26 (42%) CT scans and 16 of 27 (59%)
      scintigraphies. Twenty-six patients had a single adenoma excised while 3 patients
      with multiple endocrine neoplasia type I (MEN I) had subtotal parathyroidectomy
      for multiglandular hyperplasia during cervical exploration. Immediate
      normocalcemia was achieved in 29 patients. One patient had persistent
      hypercalcemia due to a supernumerary fifth gland in the superior mediastinum that
      was successfully excised in a second operation. One patient had a unilateral
      vocal cord paralysis and 4 patients needed calcium supplement on discharge.
      During a median follow-up of 5 months, all patients were normocalcemic with one
      requiring calcium supplements. CONCLUSION: Surgical treatment for primary HPT is
      a safe procedure and is associated with a high success rate. In our experience
      routine preoperative localization study is not cost-effective.

PMID- 9594266
TI  - Conservative management of patients with histological incomplete excision of
      cervical intraepithelial neoplasia after large loop excision of transformation
      zone.
AB  - OBJECTIVE: To evaluate conservative management of patients with histological
      incomplete excision of CIN after large loop excision of transformation zone
      (LLETZ). METHODS: Two hundred and seventeen patients with high grade CIN were
      treated with LLETZ from October 1, 1992 to December 31, 1994. Fifty-three
      patients (24.4%) had incomplete excision on histology. All patients were followed
      up cytologically every 3 to 6 months during the first 18 months and then yearly
      till December 1996. Those patients with positive endocervical margins were
      followed up with both cervical smear and endocervical smear. RESULTS: The mean
      follow-up duration was 30.4 months. Ten patients were found to have persistent or
      recurrent disease. Five patients had second LLETZ and complete excision was
      achieved in 4 of them, one patient had cone biopsy and two had hysterectomy. One
      patient was found to have stage I a cervical cancer. CONCLUSION: A report of
      incomplete excision of CIN after LLETZ calls for follow-up with cytology and
      colposcopy and not aggressive retreatment.

PMID- 9594267
TI  - An observation of the anastomoses of intrahepatic veins in normal human adults.
AB  - OBJECTIVE: To determine whether the hepatovenous intrahepatic anastomoses exist
      in normal humans. METHODS: A total of 13 livers were isolated during the early
      autopsies of normal men who died in accidents. Perfusion venography of the
      branches of hepatic veins using meglucamine diatrizoate was performed in 6 cases.
      This method of investigation has not been reported in the literature. In one
      case, a portal venography was done. In the remaining 6 cases, liver substance
      stainings were done by injecting ink through the middle hepatic vein, and the
      tissue sections of these livers were observed under light microscope. RESULTS:
      There were intrahepatic anastomoses between the hepatic veins within the liver.
      These anastomoses belonged to the 4th or 5th branch of hepatic vein near the
      capsule. There were also anastomoses between the middle hepatic vein and the
      hepatic short veins. Shunts existed between the portal veins and hepatic veins.
      CONCLUSIONS: The detection of anastomoses of intrahepatic veins in normal
      individuals provide anatomical rationale for the performance of irregular
      hepatectomy, as well as rationale for the ligation of one or two hepatic veins
      should such veins be traumatized or invaded by liver cancer.

PMID- 9594269
TI  - Correlative studies of MR findings with neuropathology in Shy-Drager syndrome and
      striatonigral degeneration.
AB  - OBJECTIVE: To determine the pathologic bases of the abnormal signal intensities
      detected on magnetic resonance imaging (MRI) in Shy-Drager syndrome (SDS) and
      striatonigral degeneration (SND). METHODS: The correlation of MRI and
      pathological findings was prospectively evaluated by postmortem scanning of the
      brain in a case of SDS and another of SND. MRI was performed by using a 1.0 T
      superconductive magnetic unit, with spin echo (SE) pulse sequences. The brain
      sections were prepared parallel to the MRI planes. The gross and microscopic
      pathological studies were conducted according to the corresponding abnormal
      signal intensities on MRI. RESULTS: In SDS, abnormal hypointense signals on T2
      weighted MR images were symmetrically demonstrated in bilateral putamen, where a
      remarkable positive Prussian blue stain reaction was revealed on pathological
      examinations. In SND, MRI showed isointense signals on T1 weighted images and
      hyperintense signals on T2 weighted images in bilateral putamen, and the
      microscopic findings included necrosis, abundant reactive fibrillary astrocytes
      and prominence of capillary vascular networks, as well as marked lipofuscin. The
      number of neurons decreased in both cases. CONCLUSIONS: The demonstration of the
      abnormal signals in the putamen on MRI is of important value in establishing an
      antemortem diagnosis of SDS and SND.

PMID- 9594268
TI  - Significance probability mapping in 45 patients with lacuna infarct.
AB  - OBJECTIVE: To find out the implications of significant probability mapping (SPM)
      in patients with lacuna infarct. METHODS: Quantitative electroencephalograms
      (QEEGs) of 45 patients with lacuna infarcts verified by computerized tomography
      (CT) were compared with mean power of different frequency bands of the healthy
      control group by Z transform. RESULTS: Thirty patients with one focus of lacuna
      infarct and 15 patients with multiple foci were verified by CT scan. Thirty
      patients had focus, and the focal abnormality was found by SPM in 22 cases, but
      only 5 cases by EEGs (P < 0.05). In multiple lacuna infarcts, focal abnormalities
      were discovered on SPM in 5 cases. Both general and focal abnormalities in the
      predominant findings were the increased power of slow frequency band. In 13 cases
      the focal abnormalities were basically in correspondence with the localization
      verified by CT scan. CONCLUSIONS: SPM could be helpful in discovering the remote
      dysfunction of cortex. The sensitivity of SPM was better than the
      electroencephalogram (EEG) and brain electrical activity mapping (BEAM).

PMID- 9594270
TI  - Advances in studies on pneumocystis carinii pneumonia in China.

PMID- 9594271
TI  - Is China an influenza epicentre?

PMID- 9594272
TI  - Transgenic mouse and chemical lesion approaches to the study of Alzheimer's
      disease.

PMID- 9594273
TI  - Biology of G protein-coupled melatonin receptors in the epididymis and prostate
      of mammals.

PMID- 9594274
TI  - The multidisciplinary treatment of cleft lip and palate in China.

PMID- 9594275
TI  - Transmission factors of schistosomiasis japonica in the mountainous regions with
      type of plateau canyon and plateau basin.
AB  - OBJECTIVE: To provide the scientific basis for formulating the control strategies
      of schistosomiasis japonica in mountainous regions in China Schistosomiasis
      Control Programme. METHODS: We selected Chuanxing Village in Sichuan Province and
      Zhonghe Village in Yunnan Province as the two pilot areas for an epidemiological
      investigation according to their geographical and topographical characteristics,
      i.e. plateau canyon and plateau basin, respectively. Concentrated-egg hatching
      method in nylon tissue bag and Kato-Katz technique were used for the survey on
      prevalence rate and intensity of infection of man and domestic animals.
      Questionnaires were applied to investigating the infection sources, community
      behavior and the socioeconomic status. Snail survey and detection of cercaria
      infested water bodies were conducted using routine techniques. RESULTS: The
      results showed that in the endemic areas with plateau canyon, the key infection
      source was cattle. The infection rate in women was higher than that in men. The
      pattern of water-pollution was wild feces and the pollution source was cattle
      feces. Snails and infectious snails were distributed over the rice fields and the
      resident was infected through production activities. In plateau basin, the key
      infection source was human beings. The infection rate in men was higher than that
      in women. The pattern of water pollution was fertilization. The pollution source
      was human feces. Snails and infectious snails were distributed over the canals
      and ditches and the resident was infected through production and daily
      activities. CONCLUSIONS: Therefore, it was suggested that the mountainous endemic
      areas should be divided into two sub-types, i.e., plateau basins and plateau
      canyons. The different control strategies should be formulated in accordance with
      the environmental situations and socioeconomic factors in the two kinds of
      endemic areas.

PMID- 9594276
TI  - Biological and clinical significance of cytogenetic study on 100 acute
      lymphoblastic leukemia and 219 acute non-lymphoblastic leukemia.
AB  - OBJECTIVE: To further investigate the role that cytogenetic may play in the
      diagnosis and prognosis of leukemia, a study was conducted in 319 acute
      leukemias. METHODS: 100 patients with acute lymphoblastic leukemia (ALL) and 219
      patients with acute non-lymphoblastic leukemia (ANLL) were from Rui Jin Hospital,
      Xin Hua Hospital, Ren Ji Hospital and Shanghai Children's Hospital. Their
      cytogenetic data were analyzed together with those of morphology, immunology and
      clinical prognosis. RESULTS: In ALL group, 48 cases were karyotypically normal
      whereas 52 cases revealed chromosomal changes, among which 32 had quantitative
      abnormalities and 20 had qualitative abnormalities. The translocation t(9; 22)
      was identified in 11 out of 20 cases of structural aberrations (55%). Specific
      structural aberrations t(9; 22) and t(8; 14) were detected to be related to B
      lineage associated differentiation antigens and t(8; 14) also with ALL-L3
      according to FAB classification. With regard to clinical prognosis, the survival
      rate of structural aberration subset decreased significantly compared with the
      normal karyotype subset (P < 0.05). However, no statistically significant
      difference was found between hyperdiploidy subset (not including near-triploidy)
      and normal karyotype subset (P > 0.75). In ANLL group, 80% of de novo patients
      and relapsed patients had chromosomal abnormalities. Importantly, structural
      aberrations accounted for 73% of these abnormalities and frequently corresponded
      to specific types of FAB classification. Relevant prognostic studies demonstrated
      that t(15; 17) subset had the best overall survival probability, followed by t(8;
      21) and normal karyotype subset, while the numerical aberration subset showed a
      relatively poor prognosis. CONCLUSION: Our data confirmed that cytogenetic study
      is important for the molecular study of the leukemogenesis. On the other hand, it
      also provides an independent parameter for prognosis in acute leukemia.

PMID- 9594277
TI  - Detection by denaturing gradient gel electrophoresis of an Arg1689Cys mutation in
      a Chinese patient with mild hemophilia A.
AB  - OBJECTIVE: To detect gene defects of factor VIII (F VIII) in Chinese hemophilia A
      patients. METHODS: 3' end of exon 14 of F VIII gene from a mild hemophilia A
      patient of Chinese origin was amplified by polymerase chain reaction (PCR) and
      identified mutations by denaturing gradient gel electrophoresis (DGGE) combining
      with direct sequencing. RESULTS: An upward shift band was detected by DGGE in
      W381. Direct sequencing demonstrated a C to T transition resulting in
      substitution of Arg1689Cys within a thrombin activation site of mature F VIII
      protein, which created a unique a thrombin activation site of mature F VIII
      protein, which created a unique PstI site in amplified fragment of F VIII.
      CONCLUSIONS: The association of PCR and DGGE can detect a single base
      substitution; the Arg1689Cys mutation that inhibited activation of F VIII by
      thrombin is a molecular defect associated with hemophilia A in W381.

PMID- 9594278
TI  - Multiprimer--PCR for screening of IgH and T-cell receptor rearranged genes in
      acute lymphoblastic leukemia.
AB  - OBJECTIVE: To develop a multiprimer-polymerase chain reaction (multiprimer-PCR)
      method for detecting immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)
      rearranged genes in the same amplification. METHODS: Multiprimer-PCR protocol, a
      mixture of four different primers used in the same reaction detected IgH CDR-III
      and TCR V gamma I-J gamma Ligenetic rearrangements in 40 acute lymphoblastic
      leukemia (ALL) patients. RESULTS: Thirteen cases were found to have IgH CDR-III
      and TCR V gamma I-J gamma genetic rearrangements. Ten cases were found to have
      TCR V gamma I-J gamma genetic rearrangements. Thirteen cases were found to have
      IgH CDR-III genetic rearrangements. The amplification result of multiprimer-PCR
      was the same as separate amplification. The sensitivity of multiprimer-PCR was
      10(-4)-10(-5) DNA level, which was the same as separate PCR amplification. All
      positive cases with IgH rearranged gene were confirmed by Southern blot.
      CONCLUSION: Multiprimer-PCR could screen two distinct rearranged genes in a
      single amplification, and is more suitable for screening of specimens collected
      at diagnosis.

PMID- 9594280
TI  - Diagnosis and treatment of solid brainstem tumors in adults.
AB  - OBJECTIVE: To evaluate the diagnosis and aggressive surgical approach for
      brainstem tumors. METHODS: A series of 24 adult patients with brainstem tumors
      were involved. Magnetic resonance (MR) imaging was performed on all patients.
      Surgical technique, potential risk and management of complications were
      described. RESULTS: Diagnosis was confirmed by MR imaging and histological
      examination in all the patients. Tumors were totally or subtotally removed in
      twenty-two patients. Signs and symptoms were improved in 19 patients on
      discharge. CONCLUSIONS: Our study shows that MR imaging has an important value
      for localizing tumors, identifying their nature and selecting appropriate
      surgical approaches. Most brainstem tumors, except for high-grade gliomas and
      small ventral tumors, are amenable to an aggressive surgical approach. The
      favorable results depend upon the appropriate surgical approach, microsurgical
      technique and intensive care after operation. Total removal can provide both high
      quality survival and favorable long-term prognosis.

PMID- 9594279
TI  - Change of level and expression of endothelin-1 in the lungs of rats with hypoxic
      pulmonary hypertension.
AB  - OBJECTIVE: To determine whether mRNA for endothelin-1 was present and changed in
      the lungs of rats exposed to chronic hypoxia. METHODS: cRNA probes for rat ET-1
      and c-fos were labelled by in vitro transcription with digoxigenin-UTP for in
      situ hybridization. Endothelin-1 like immunoreactivity (ET-1-LI) in plasma as
      well as in lung homogenate was measured by radioimmunoassay. RESULTS: The
      vascular endothelial cells of pulmonary arteries and the bronchiolar epithelial
      cells were strongly positive for the ET-1 probe. The perivascular and
      peribronchiolar smooth muscle were positive for the c-fos probe, primarily. There
      was little expression of ET-1 and c-fos in the rat lungs in controls. There was
      significant increase of ET-1-LI levels in rats exposed to hypoxia for 3 weeks,
      the concentration ET-1-LI in venous samples was 3.85 +/- 1.52 ng/L (P < 0.05 as
      compared with the control groups), in arterial sample was 4.72 +/- 1.66 ng/L (P <
      0.05) and in lung was 2.06 +/- 0.68 ng/g wet lung weight (P < 0.05). CONCLUSIONS:
      Chronic hypoxia elevated the mean pulmonary arterial pressure, caused vessel
      remodelling and the right ventricular hypertrophy. These changes were accompanied
      by an increase of ET-1 in plasma and lung homogenate. The expression and
      production of ET-1 were localized to endothelium and airway epithelium in the
      lungs.

PMID- 9594281
TI  - Postoperative immunotherapy for patients with hepatocarcinoma using tumor
      infiltrating lymphocytes.
AB  - OBJECTIVE: To explore a more effective immunotherapy for cancer by studying tumor
      infiltrating lymphocytes (TIL) of patients with hepatocarcinoma. METHODS: TIL
      isolated from freshly resected tumors of 12 patients with hepatocarcinomas were
      activated, expanded and cultured in vitro by incubation with interleukin-2, and
      then infused to the patients. The TIL cytotoxicity and phenotype were determined
      by MTT and immunohistochemical ABC methods. RESULTS: The average weight and
      number of cells of the tumor tissues for culture of TIL were 4.8 g and 5.8 x
      10(7) respectively, and the median expansion time was 31.8 days in vitro. The
      maximal expansion achieved 1000 fold, and the mean amplification rate was 198.5
      fold. Lymphokine-activated killer cell culture supernatant could stimulate TIL
      growth. Ten of 12 patients received immunotherapy of TIL. The number of cells
      infused reached 4 x 10(8)-1.1 x 10(10). In 3 cases of our series, TIL infusions
      were done through a drug pump with a catheter embedded in the hepatic artery.
      Eight patients whose primary hepatic carcinomas were resected completely were
      followed up for 16 months with only one case (12.5%) having recurrence. The
      recurrence rates of them at 6 and 12 months after tumor resection were remarkably
      lower than those of the patients who did not receive TIL infusion (19.4% and
      41.6%, respectively). One patient whose tumor was not able to be removed received
      TIL infusion twice and local alcohol injection several times. He has been alive
      for 9 months. CONCLUSIONS: TIL isolated from the tumors of patients with
      hepatocarcinoma can be activated and expanded in vitro. It demonstrated
      remarkably cytotoxic activity against tumor targets. TIL infusion is an effective
      immunotherapy for patients with hepatocarcinoma in reducing recurrence after
      operation.

PMID- 9594282
TI  - Oxygen free radical injury and its relation to bacterial and endotoxin
      translocation after delayed fluid resuscitation: clinical and experimental study.
AB  - OBJECTIVE: To examine whether there is generation of oxygen free radicals (OFR)
      and lipid peroxidation of cell membrane after volume replacement for burn shock,
      and to study the relationship between OFR injury and enterogenous endotoxemia.
      METHODS: Forty-seven burn patients were involved in this study. Among them, 18
      had delayed fluid resuscitation (DR) and the others had early fluid resuscitation
      (ER) within 6 hours postburn. Sixty-six gnotobiotic rats were used in a
      collaborating experiment as burn models. They were divided into 4 groups: sham
      injury (n = 6), early resuscitation (n = 24), late resuscitation (n = 24) and
      vitamins E and C treatment group (n = 12). All the rats, except those in the sham
      injury group, were inflicted with 40% total body surface area (TBSA) third-degree
      burns. OFR was determined in the blood of patients with electron spin resonance
      (ESR). S/W ratio and tau c values of patients' erythrocytes were measured with
      ESR spectrometer. Blood superoxide dismutase (SOD) and glutathione peroxidase
      (GSHPx) activities, malondialdehyde contents and plasma endotoxin levels were
      assayed. Rats were sacrificed at the 12th, 24th, 48th and 72nd hour after injury.
      Plasma endotoxin levels, mucosal SOD, GSHPx and malondialdehyde (MDA), as well as
      diamine oxidase activity of ileum were determined. Cultures of mesenteric lymph
      nodes (MLN), liver, spleen, heart, lung, kidney and blood were done. RESULTS: A
      significant increase in blood OFR contents and plasma MDA, and a significant
      decline in blood SOD and GSHPx were found after resuscitation in DR group as
      compared with those in ER group. Both strong to weak spectra component (S/W)
      ratio and tau c value were higher in DR group in contrast with those in ER group.
      Higher elevation in plasma endotoxin level in DR group was seen. In DR group,
      plasma MDA content was correlated with S/W ratio, tau c value and plasma
      endotoxin level. In rats, the level of mucosal MDA, plasma endotoxin and
      incidence of bacterial translocation (BT) were significantly higher. Mucosal SOD,
      GSHPx and diamine oxidase (DAO) activity were significantly lower in DR group as
      compared with those in ER group. In DR group, mucosal MDA content was negatively
      correlated with mucosal DAO activity, while the latter was negatively correlated
      with BT. After treatment with vitamins E and C, mucosal MDA content decreased,
      plasma endotoxin and BT significantly declined and mucosal DAO heightened.
      CONCLUSIONS: Tissue reperfusion might induce the production of OFR, resulting in
      lipid peroxidation injury, especially to intestinal mucosa, and resulting in
      disruption of mucosal barrier function followed by endotoxemia and BT.

PMID- 9594283
TI  - Fibula grafting for treatment of aggressive benign bone tumor and malignant bone
      tumor of extremities.
AB  - OBJECTIVE: To compare the effect of vascularized and nonvascularized fibula
      grafting performed for the reconstruction of bone defects after the resection of
      bone tumors. METHODS: Vascularized fibula grafting was performed in 18 patients
      with malignant or aggressive benign bone tumor of the extremities. Non
      vascularized fibula grafting was performed in 15 patients with giant cell tumor
      of the radius. All the 18 patients were followed up with radiography, single
      photon emission computed tomography (SPECT), colored Doppler's sonography (CDS)
      examinations and functional observation for 2 to 14 years. RESULTS: Vascularized
      fibula grafts with bone defects of 9 to 26 cm showed good blood supply in
      emission computerized tomography (ECT) and radiography examinations, and bone
      union was achieved (Table 1). In non-vascularized fibula grafting cases (Table
      2), bone union was not achieved. CONCLUSIONS: The advantages of vascularized
      grafting are the feasibility of one-stage reconstruction of various tissues and
      the growth of grafted fibula. It is necessary to adopt vascularized fibula
      grafting to reconstruct large bone defect resulting from the resection of
      extensive bone tumors, such as giant cell tumor (GCT), fibrous dysplasia of bone
      and malignant bone tumors.

PMID- 9594284
TI  - Quantitative analysis of light sensitivities in central 30-degree visual field of
      normal Chinese and glaucoma patients.
AB  - OBJECTIVE: To examine the difference in the light sensitivity in the central
      visual field between the normal subjects and patients with or without the early
      visual field damages and propose the criteria to identify the possible early
      disturbances in the visual field. METHODS: Light sensitivities at the 76
      locations in the central field were measured in 108 normal eyes of 75 normal
      volunteers aged from 20 to 78 years, and 82 eyes of 53 patients with early open
      angle or closure-angle glaucoma on the Humphrey Field Analyzer (Model 610), using
      the Central-30-2 program. RESULTS: No sex and eye differences were found. The
      significant differences in the light sensitivities existed between the age of 20
      45 years and the age of 46-78 years in the normal subjects. The lower limit of
      80% normal range for each location in the central field of the two age groups was
      calculated. The light sensitivity decreased by 2-3 dB at every 10 degree from the
      eccentricity. The light sensitivity in the inferior field was 1-2 dB higher than
      that in the superior field. There was no statistical difference between the nasal
      and the temporal field. For the patients with the field defects, the light
      sensitivity of many locations decreased by 4-8 dB, and by 1-2 dB in the patients
      without the field defects as compared with the normal controls. CONCLUSIONS:
      Based on comparisons with the normal controls and the lower limit of 80% normal
      range, we proposed the following criteria for classification of the damages in
      the glaucoma visual field. Grade I: light sensitivity reduces by 1-3 dB at a
      cluster of locations in the field; Grade II: light sensitivity reduces by 4-6 dB
      at a cluster of locations in the field; Grade II: light sensitivity reduces by
      more than 6 dB at a cluster of locations in the field.

PMID- 9594285
TI  - Changes in tachykinin--ergic nerve terminal densities in rat nasal mucosa during
      hypersensitivity.
AB  - OBJECTIVE: To further carry out a quantitative immunohistochemical study on
      neuropeptides (NPs) participation in perennial allergic rhinitis (PAR) in nasal
      mucosa. METHODS: By using light microscopy (routine hematoxylin and eosin
      staining, Wright's staining and 1% toluidine blue staining) and scanning as well
      as transmission electron microscopy, an exhaustive immunohistochemical and
      morphometric study was made on the changes of substance P (SP), neuropeptide A
      (NKA) and neuropeptide B (NKB) in the nasal mucosa of a toluene-2,4-iso-cyanate
      (TDI)-induced PAR model of rat. RESULTS: The results showed that the densities of
      all three peptidergic terminals were significantly increased (P < 0.01) in
      experimental group (115.72 +/- 28.43 for SP, 39.23 +/- 10.34 for NKA and 37.24 +/
      11.22 for NKB, respectively) as compared with those in control group (49.65 +/-
      11.23 for SP, 12.44 +/- 6.21 for NKA and 13.31 +/- 7.60 for NKB, respectively).
      Increased staining, thickening of peptidergic terminals and enlargement of
      varicosities were found. Mast cell infiltration in nasal mucosa was in parallel
      with increase of peptidergic terminals. CONCLUSION: All results support the
      hypothesis that NP is a newly-recognized but potentially important factor in the
      pathogenesis of PAR.

PMID- 9594286
TI  - Otoacoustic emission and auditory efferent function testing in patients with
      sensori-neural hearing loss.
AB  - OBJECTIVE: To examine the role of otoacoustic emissions and auditory efferent
      system function in evaluating auditory functional status in both normal and
      diseased conditions. METHODS: Spontaneous and transient evoked otoacoustic
      emissions and efferent function in terms of contralateral white noise induced
      transient evoked otoacoustic emission suppressions were tested and cross compared
      in 32 normal ears, 24 ears with cochlear hearing loss and 16 ears with
      retrocochlear hearing loss. RESULTS: Transient evoked otoacoustic emission
      amplitude and contralateral suppression, spontaneous otoacoustic emission
      incidence, peaks and frequency range were significantly reduced in cochlear
      hearing loss while in retrocochlear hearing loss transient evoked otoacoustic
      emission and spontaneous otoacoustic emission levels were significantly higher
      than in cochlear hearing loss group and showed no suppression. CONCLUSIONS:
      Contralateral acoustic stimulation induced transient evoked otoacoustic emission
      suppression as an index of efferent function is clinically feasible. Combined
      otoacoustic emission and efferent tests are of great significance in evaluating
      cochlea status and auditory central mechanisms. Auditory efferent function is
      weakened in cochlear lesions and severely damaged in retrocochlear lesions.

PMID- 9594287
TI  - Expression of antimetastatic gene nm23-H1 in epithelial ovarian cancer.
AB  - OBJECTIVE: To investigate the expression of nm23-H1 in epithelial ovarian cancer.
      METHODS: A total of 55 specimens from patients with epithelial ovarian cancers,
      15 patients with serous cancers, 7 with mucinous cancers, 17 with endometrioid
      cancers and 16 with adenocarcinomas, were examined for the expression of nm23-H1
      by means of the immunohistochemical technique. RESULTS: The total positive rate
      was 23.64% (13/55). The tissular nm23-H1 immunostaining had significantly higher
      expression in mucinous cancer (57.14%) than in other histologic types of
      epithelial ovarian cancer (P < 0.05). Compared to that in the primary tumor, nm23
      H1 expression in the omental metastatic tumor in the same patient was reduced.
      CONCLUSIONS: The expression rate of nm23-H1 is higher in the primary tumors than
      in the metastatic tumors and is different in various histologic subtypes of
      epithelial ovarian cancer. The expression of nm23-H1 may participate in the
      inhibitory process of tumor invasion.

PMID- 9594288
TI  - A preliminary study on interruption of HBV transmission in uterus.
AB  - OBJECTIVE: The infection of Hepatitis B virus (HBV) in the uterus may occur in
      neonates born to HBV carrier mothers. The rates of intrauterine transmission in
      these neonates were 10%-16%, Recent studies on the methods of combined passive
      and active immunizations indicate an efficacy approaching 70%-90%, but
      intrauterine infection of HBV is the major cause of failure of vaccination to
      combat hepatitis B in neonates born to HBV carrier mothers. We studied the
      interruptive effect of HBV specific immunoglobulin (HBIG) before delivery in the
      prevention of intrauterine transmission of HBV. METHODS: Of 3632 pregnant women,
      two hundred and four were HBV carriers; they were randomly divided into an HBIG
      group and a control group. Each subject in the HBIG group received 200 IU of HBIG
      intramuscularly at 3, 2 and 1 month before delivery. The subjects in the control
      group did not receive any specific treatment. Blood tests were conducted for all
      the subjects and their neonates after birth. Blood specimens were tested for
      HBsAg and HBeAg by enzyme immunoassay (Abbott Kits). RESULTS: The results showed
      that the rates of intrauterine transmission in the two groups were 5.7% and 14.7%
      respectively (X2 = 4.58 P < 0.05). No significant differences were observed for
      the positive rates of HBsAg and HBeAg between the two groups after delivery, but
      titer of HBsAg was reduced significantly in the HBIG group (t = 4.82, P < 0.01).
      CONCLUSIONS: Our study suggests that HBV infection in the uterus may be
      interrupted using multiple HBIG intramuscularly before delivery without any side
      effects.

PMID- 9594289
TI  - Comparison of birth weight by gestational age between China and the United
      States.
AB  - OBJECTIVE: To probe into the similarities and differences of birth weight by
      gestational age between China and the United States by a comparative study.
      METHODS: For China, we used the records of 24,150 single livebirth neonates.
      These records were collected between February 1986 and May 1987 from 43 hospitals
      and health care units in 15 large and middle cities in the South and North of
      China. For the United States, we used the natal records of National Center for
      Health Statistics from 1980 to 1987, selecting infants whose parents were coded
      as white and with higher socioeconomic backgrounds in the birth records. A total
      of 6,295,102 singleton livebirth neonates were selected. We used a method based
      on probability plots to define birth weight distributions. RESULTS: The 50th and
      95th percentiles of birth weights by gestational age of American newborns with
      white parents were more than those of Chinese newborns. The 50th percentile
      values of birth weights of American male and female newborns were 357 g and 277 g
      (about 10% and 8% respectively of the birth weight of a term newborn) more than
      those of Chinese male and female newborns respectively at 40 weeks of GA.
      CONCLUSIONS: American white newborns were heavier than Chinese newborns. The
      differences were mainly due to race-specific influences, and were related to the
      differences in socioeconomic and educational background. We suggest that the
      references of birth weight by gestational age should be formulated separately in
      China and in the U.S.

PMID- 9594290
TI  - A study of cerebral blood flow velocity in pregnancy induced hypertension.

PMID- 9594291
TI  - Studies of needling depth in acupuncture treatment.
AB  - OBJECTIVE: To investigate safety and De-qi (obtaining of needling sensation)
      depth of acupoint and their relation to therapeutic effect, and to electric
      resistance. METHODS: 1) We plotted the graph to compare the differences of each
      acupoint depth between modern and ancient acupuncture writings; 2) 80 cadavers,
      and 240 subjects with computer tomography of chest to study the safety depth of
      acupoint were used, and their correlation to the length of the second phalanx of
      middle finger as Tong Shen Cun's standard; 3) 300 subjects were divided according
      to their body height and weight into normal-weight, over-weight and under-weight
      groups of 100 subjects to study the De-qi depth of acupoint; 4) using the 120
      subjects which accepted acupuncture treatment due to pain symptom to study the
      relation between De-qi depth and therapeutic effect; 5) 107 subjects of different
      sizes were used to study the relation between De-qi depth and thickness of body,
      and electric resistance. RESULTS: Acupoint depth was greater in modern
      acupuncture writings than in ancient writings. The safety depth of each acupoint
      in chest and in back was different, and they had high correlation to Tong Shen
      Cun's standard in adults, but not in newborns. The safety depths in chest
      acupoints were greater in female than in male, but not in back, and they related
      to body size. The De-qi depth was correlated with their therapeutic effects,
      corresponding to body thickness, but not related to their electric resistance.
      CONCLUSIONS: Safety and De-qi depth of acupoint are related to body thickness.
      The length of the second phalanx of middle finger may be used as Tong Shen Cun's
      standard in adults, but not in newborns.

PMID- 9594293
TI  - China's pediatric surgery and her young pediatric surgeons.

PMID- 9594292
TI  - Multiple antibiotic-resistant lactic acid bacteria preparation eliminated MRSA
      from the decubitus of a bed-ridden elderly patient.

PMID- 9594295
TI  - Pathological classification and diagnosis of intestinal duplication.
AB  - OBJECTIVE: To determine the pathological classification and the clinical
      characteristics of intestinal duplication. METHODS: Eighty-four pediatric
      patients with intestinal duplication were proved on operation in the last 20
      years in the Second Hospital of Harbin Medical University and Harbin Children's
      Hospital. The pathological classifications were as follows: enteral septum type
      (2), parietal cyst type (9), parenteral canal type (31), parenteral cyst type
      (35), and solitary type (1). The clinical presentations and complications
      included: abdominal mass (24), illius (41), hemorrhage of digestive tract (15)
      and intestinal perforation with peritonitis (3). Two asymptomatic cases were
      discovered incidentally. RESULTS: Among the 84 patients, 82 healed, 1 newborn
      complicated by intestinal fistula died of septicemia, and the other one died of
      toxic shock. CONCLUSIONS: Recognizing the pathological types, common
      presentations and complications, and applying the corresponding examination
      methods timely, doctors may improve the diagnostic accuracy.

PMID- 9594294
TI  - The tension-stress effects on growth of the external anal sphincter: animal
      experiment and its application on treatment of anorectal stenosis.
AB  - OBJECTIVE: To evaluate the effect of continuous balloon distension on the
      treatment of anorectal stenosis. METHODS: Animal experiment on 17 guinea pigs and
      clinical study on 13 patients with anorectal stenosis were carried out. The
      procedure of the continuous balloon distension was followed to stimulate the
      growth of the anus or stenotic segment. RESULTS: In animal experiment, the
      procedure induced muscle growth of the external anal sphincter at a rate of 2 mm
      per day. The grown muscle showed good contractile ability. By histological
      examination, it was found that the muscle cells were hypertrophic and Schwann's
      cells of the nerve fibers in the muscle became hyperplastic. Under electron
      microscope, the muscle sarcomeres were found splitting both transversely and
      longitudinally. Twelve of the 13 patients were successfully treated by continuous
      balloon distension within 5 to 15 days (average: 6.7 days). During 4 to 14 months
      follow-up, all patients defecated without difficulty. CONCLUSIONS: Continuous
      balloon distension may induce growth of the external anal sphincter. This
      procedure is an acceptable therapy for anorectal stenosis.

PMID- 9594296
TI  - A study on cholangitis after hepatic portoenterostomy for biliary atresia.
AB  - OBJECTIVE: To investigate the clinical manifestations and factors relating to
      prognosis in biliary atresia (BA). METHODS: Twenty-four cases were reviewed on
      clinical manifestations and bile flow after operation. All patients underwent
      hepatic portoenterostomy. RESULTS: Twenty-three cases (95%) got bile flow
      postoperatively. Sixteen (69%) of 23 patients had 27 episodes of cholangitis.
      There were significant differences (P < 0.05) in the amount and bilirubin
      concentration of bile flow before and after cholangitis. Cholangitis also
      affected the life quality of BA patients. CONCLUSION: We consider that early
      finding and prevention of cholangitis can improve the prognosis of BA patients.

PMID- 9594297
TI  - Mucosa cell regeneration following intestinal ischemia/reperfusion injury in
      rats.
AB  - OBJECTIVE: To evaluate regeneration and proliferation of the mucosa cells
      following intestinal ischemia/reperfusion (I/R) injury. METHODS: Sixty rats (200
      250 g) were examined after intestinal I/R injury with immunohistochemical (BrdU)
      method and flow cytometric analysis. RESULTS: Severe damage to the villi was
      evident at 2 hours reperfusion and the rate of cell proliferation was lower (P <
      0.01). All the specimens has healed mucosa with re-epithelialized villi tips
      after 2 days regeneration, but the villi were scarce and tiny. After two and four
      days regeneration, the rate of cell proliferation was significantly higher than
      that of controls (P < 0.01). CONCLUSIONS: Our study suggests that the intestinal
      regeneration following I/R injury in rats occurs early. The immunohistochemical
      method with BrdU-labeled technique is a rapid method for quantifying the rate of
      cellular DNA synthesis.

PMID- 9594299
TI  - Evolutionary regularity of acetabular dysplasia after reduction of developmental
      dislocation of the hip.
AB  - OBJECTIVE: To observe the developmental changes of the acetabulum after reduction
      of developmental dislocation of the hip and require evolutionary regularity of
      acetabular dysplasia. METHODS: A follow-up in an average of 7.4 years was carried
      out in 117 patients (161 hips) with developmental dislocation of the hip after
      reduction. By the series of X-ray films, acetabular index, acetabular-head index,
      Sharp's angle, ACM angle (Idelberger's angle) and anteversion were observed. At
      the same time, centre-head distance discrepancy was measured. RESULTS: Acetabular
      index returned to normal gradually as the time went by and significantly within
      one year after the reduction of developmental dislocation of the hip. The process
      of recovery was nearly stable three years later. Acetabular index in the
      dysplasia group was above 39 degrees before reduction and decreased slowly after
      the reduction. However, it was still up to 30 degrees after 3 years observation.
      The value of centre-head distance discrepancy decreased gradually as the years
      went by after reduction. CONCLUSIONS: If acetabular index before reduction is
      above 39 degrees and is still up to 30 degrees three years after reduction,
      acetabular dysplasia can be diagnosed.

PMID- 9594298
TI  - Detection of neuroblastoma cells in blood by reverse transcriptase-polymerase
      chain reaction.
AB  - OBJECTIVE: To determine whether circulating tumor cells are present in patients
      with localized or disseminated neuroblastoma (NB). METHODS: Sixteen pediatric
      malignant tumor cell lines, including 10 NB, 4 primitive neuroectodermal tumor
      (PENT), 2 Wilms' tumor and 39 samples (tumor tissue, bone marrow and peripheral
      blood) from 8 patients with NB, were evaluated by reverse transcriptase
      polymerase chain reaction (RT-PCR) using two markers: neuroendocrine protein gene
      products 9.5 (PGP 9.5) and tyrosine hydroxylase (TH). RESULTS: Analysis of RT-PCR
      products by agarose electrophoresis demonstrated that in culture cell lines the
      specificity for NB was highest in TH (9/10 with NB, 3/4 with PNET, 0/2 with
      Wilms' tumor) and the sensitivity was highest in PGP 9.5 10(-7). PGP 9.5 and TH
      mRNA were undetectable in the peripheral blood mononuclear cells (PBMNC) from
      normal children. Expression of these markers in 8 patients with NB at diagnosis
      and during treatment was found positive in 5 out of 8, all had been proved
      paralleling with their disease status. Two of the 5 became negative after further
      treatment. CONCLUSIONS: These systems allow the detection of circulating NB cells
      with higher sensitivity and specificity. When RT-PCR is clinically used for the
      detection of NB cells in blood, that both PGP 9.5 and TH should be selected is
      recommended. The assessment of bone marrow alone might not be used as a single
      index of tumor dissemination.

PMID- 9594300
TI  - Sex hormone receptors of hemangiomas in children.
AB  - OBJECTIVE: To investigate whether or not estrogen receptor and other sex hormone
      receptors are present in hemangioma tissues of children. METHODS: Fifty-two
      specimens of hemangiomas were taken from 52 children. The specimens were doubly
      stained with hematoxylin-eosin and enzyme-linking affinity immunohistochemistry.
      The prepared tissue slides were observed under the microscope to search for
      estrogen receptors (ER), progestogen receptors (PR) and androgen receptors (AR)
      in all the cells. RESULTS: ER, PR and AR were detected in various kinds of
      hemangiomas. The mean positive cell rate of each sex hormone receptor in
      different hemangioma tissues revealed no significant distinction in statistics (P
      > 0.05). CONCLUSIONS: The results suggest that hemangiomas are one of the target
      tissues of estrogen. Estrogen, ER, PR, and AR may play an important role in the
      growth and development of hemangiomas.

PMID- 9594301
TI  - Expression of proliferating cell nuclear antigen in Wilms' tumor.
AB  - OBJECTIVE: To investigate the expression of proliferating cell nuclear antigen
      (PCNA) and its clinical significance in Wilms' tumor. METHODS: PCNA
      immunoreactivity on paraffin-embedded tissues was assessed retrospectively in 35
      cases using labelled streptaridin biotin (LSAB) procedure, and its association
      with clinical and other biological features was studied. RESULTS: Twelve tumors
      (34.29%) expressed PCNA. Expression rate increased with the advance of stage (P <
      0.05). The S-phase fraction and proliferation index (PI) in children with PCNA
      positive expression were higher than those in children with negative PCNA
      expression (P < 0.05). The survival rate (16.67%) in patients with positive PCNA
      expression was significantly lower than that (73.91%) in no-expression ones (P <
      0.01). CONCLUSION: PCNA is a sensitive indicator for cell proliferation and is
      clinically useful in identifying a poor prognostic group of patients with Wilms'
      tumor.

PMID- 9594302
TI  - An animal experiment on short gut lengthening.
AB  - OBJECTIVE: To investigate the anatomical and histological changes of the
      lengthened gut by a special intraluminal tubular expander on the basis of the
      theory of "tension-stress". METHODS: Nineteen New Zealand white rabbits were
      used. A 5 cm segment of the terminal ileum with a pedicle was put underneath the
      abdominal wall, with its proximal end closed and its distal end exteriorized as a
      stoma. One week later, as the wound healed well, an expander made of a small
      rubber tube was inserted into the short gut loop through the stoma. Three
      milliliters of water was injected as an initial dose. Then 0.5 ml water as an
      increment was injected subsequently every 12 hours until the total amount of
      water reached 15 ml and kept stable for two weeks. RESULTS: Anatomically, the
      length and the capacity of the intestinal loop were recorded, after 15 ml
      expanding, as an average of 150% lengthening of the original and an average of
      293% expansion. Two weeks after the removal of the expander, partial shrinking
      was observed. A stable lengthening had 123% of the original length, while the
      capacity reduced to 200% of the original one. Histologically, there was no
      remarkable changes of the mucosa or submucosa. But significant hypertrophy of the
      musculature and serosa layer was observed. The total thickness of the
      musculatures was 618% of the normal control's. Ultrastructurally, there were
      enlargement of the smooth muscle cells, increase in number and size of the
      mitochondria in the cytoplasm and widening of the intercellular space.
      CONCLUSION: A short gut can be lengthened by a tubular expander following the
      rule of gradual tension and stress.

PMID- 9594303
TI  - Nitric oxide synthase distribution in the enteric nervous system of children with
      cardiac achalasia.
AB  - OBJECTIVE: To study the distribution of nitric oxide synthase (NOS) in the
      enteric nervous system of children with cardiac achalasia. METHODS: Biopsy
      specimens of the lower esophagus, cardia, gastric fundus and pylorus from 13
      patients with cardiac achalasia and 6 controls were obtained and studied
      histochemically with nicotinamide adenine dinucleotide phosphate diaphorase
      (NADPH-d) and immunohistochemically with a specific polyclonal antiserum.
      RESULTS: NOS was abundant in the myenteric plexus and the nerve fibers of
      musculatures in the esophagus, cardia and gastric fundus in control group, while
      it was nearly absent in the patient group. The distribution of NOS in the pylorus
      was similar in the two groups. CONCLUSION: These findings suggest that a lack of
      NOS in the lower esophagus, cardia and gastric fundus is involved in the
      pathophysiology of cardiac achalasia in children.

PMID- 9594304
TI  - Immunoreactive growth hormone in human peripheral T lymphocytes: encoding
      sequence of cDNA identical to that of the pituitary human growth hormone.
AB  - OBJECTIVE: To detect the cDNA sequence of immunoreactive growth hormone (irGH) in
      human lymphocytes and to compare it with that of human growth hormone (hGH) in
      the pituitary. METHODS: The mRNA of irGH in human peripheral blood mononuclear
      cells (PBMC) was detected by Northern blot analysis. The cDNA of irGH was
      obtained by reverse-transcriptase and polymerase chain reaction amplification and
      obtained by screening from a cDNA library of human T lymphocytes. The sequence of
      irGH cDNA was determined and compared with that of the pituitary hGH. RESULTS:
      Very low level of irGH mRNA was detected in human PBMCs by Northern blot
      analysis. The cDNA sequence of the entire open reading frame of human irGH was
      651 bp, which is identical to that of pituitary hGH. CONCLUSIONS: The same hGH
      molecule can be produced by human pituitary somatotrophic cells and human
      peripheral lymphocytes.

PMID- 9594305
TI  - Polymorphisms of vitamin D receptor gene and its association with bone mineral
      density and osteocalcin in Chinese.
AB  - OBJECTIVE: To explore the distribution frequencies of vitamin D receptor (VDR)
      gene polymorphisms in Chinese and the relationship between VDR genotypes and bone
      mineral density (BMD) or serum osteocalcin level in Chinese women. METHODS:
      Polymorphisms of VDR gene were analyzed by polymerase chain reaction (PCR) to
      amplify the DNA sequence and three restriction enzymes (namely BsmI, ApaI and
      TaqI) to digest the PCR products in 223 subjects. Some of the VDR genotypes were
      also confirmed by Southern hybridization analysis. BMD was measured at the spine
      and proximal femur by dual-energy X-ray absorptiometry (DEXA). Serum osteocalcin
      concentrations were determined by radioimmunoassay. RESULTS: Chinese had high
      frequencies of "b,a,T" alleles, 95%, 75% and 95% respectively, which were much
      different from Caucasians. "BB" or "AA" genotype had tendency for higher BMD at
      some sites in the group of young women, whereas in the group of postmenopausal
      women, "bb" or "aa" genotype had relationship with lower BMD at femoral neck and
      trochanter. Furthermore, no relationship were found between VDR genotypes and the
      serum osteocalcin level in Chinese women. CONCLUSIONS: Allele frequencies of VDR
      gene in Chinese are different from those in Caucasians. VDR gene polymorphisms
      are associated with BMD in Chinese, but in a different pattern from other
      reports. Further study on predicting function of VDR for osteoporosis is
      necessary.

PMID- 9594306
TI  - Mitochondrial tRNA(Leu(UUR)) gene mutation diabetes mellitus in Chinese.
AB  - OBJECTIVE: To ascertain the prevalence and clinical features of mitochondrial
      tRNALeu(UUR) gene nucleotide (nt) 3243 A-->G mutation diabetes mellitus in
      Chinese and to establish the approaches for genetic diagnosis of this subtype of
      diabetes during routine daily clinical practice. METHODS: Mitochondrial nt 3243 A
      ->G mutation was screened among 207 unrelated non-insulin-dependent diabetes
      mellitus (NIDDM) patients by using polymerase chain reaction (PCR)/Apa I
      restriction endonuclease digestion. Samples with positive result were confirmed
      by DNA sequence analysis. Genetic and clinical analysis were carried out in
      family members of the proband with positive genetic diagnosis. RESULTS: Positive
      results were found in two subjects during screening of unrelated NIDDM patients,
      which account for 2.4%-11.1% of NIDDM subjects with uncommon clinical features
      (with early age-of-onset, with low body-mass-index and on insulin therapy) or
      with positive family history of diabetes consistent with or unable to exclude
      from maternal inheritance. Genetic diagnosis was positive in 10 out of 25 family
      members in the pedigrees of these two probands. CONCLUSIONS: Mitochondrial
      tRNALeu(UUR) gene nt 3242 A-->G mutation should be considered in diabetic
      patients with the above-mentioned clinical features. The genetic diagnosis in
      daily clinical practice can be performed with allele specific priming
      amplification, or PCR/Hae III or Apa I digestion which are technically simple to
      perform and diagnostically easy to define.

PMID- 9594307
TI  - Effectiveness of electrochemical therapy in the treatment of lung cancers of
      middle and late stage.
AB  - OBJECTIVE: To investigate the effect of electrochemical therapy (ECT) in the
      treatment of middle and late-stage lung cancers. METHODS: Three hundred and
      eighty-six cases (287 males md 99 females aged 25-78, with an average age of 51
      years) with middle and late-stage lung cancers were treated with ECT. Two hundred
      and three patients had squamous cell carcinoma, 138 adenocarcinoma and 45
      undifferentiated cancer. Diameters of the cancers were respectively 4.0-6.0 cm in
      153 cases, 6.1-8.0 cm in 82 cases, 8.1-10.0 cm in 102 cases and over 10.0 cm in
      49 cases. In this group, none was at stage I, 103 cases were at stage II, 89
      cases at IIIa, 122 cases at IIIb and 72 cases IV. Of the 386 cases, 152 cases
      (39.4%) also suffered from hypertension, heart disease etc. Anode and cathode
      platinum electrodes were inserted accurately into the tumour mass. Distance
      between two electrodes was 2.0-2.5 cm. Electrodes were connected to a special ECT
      instrument. The current was maintained at 6-8 V and 80-100 mA. One hundred
      coulombs are used for treating 1 cm diameter of tumour mass. RESULTS: Of the 386
      cases, 99 cases (25.6%) achieved complete remission (CR). 179 cases (46.4%)
      achieved partial remission (PR), 59 cases (15.3%) had no change (NC) and 49 cases
      (12.7%) had progression of disease (PD). Effective rate CR + PR) was 72% (278
      cases). One to five year survival rates were 86.3%, 76.4%, 58.8%, 39.9% and
      29.5%, respectively. CONCLUSIONS: ECT is easy to use. It is effective, safe, less
      traumatic and makes patients recover quickly. This is a new and effective method
      to treat patients with tumours who are inoperable and can not receive
      chemotherapy or radiotherapy.

PMID- 9594308
TI  - Gallstones and their chemical types in relation to serum lipids and
      apolipoprotein levels.
AB  - OBJECTIVE: To determine the profile of lipidemia in patients with gallstones and
      the characteristics of lipidemia in different kinds of gallstone in gallbladder
      for predicting high risk subjects predisposed to gallstone formation by means of
      some serum parameters. METHODS: Serum lipids and apolipoproteins levels in 47
      patients with stone in gallbladder (stone group) were compared with those in 19
      inpatients without stone (control group). The characteristics of lipidemia in
      different kinds of gallbladder stones were also compared. RESULTS: Serum
      apolipoprotein (Apo) A1, C2 and E levels in the stone group significantly
      increased as compared with the control group (P < 0.01), but there were no
      statistically significant differences in TC, TG, LDL-C, HDL-C, HDL-C/TC, LDL
      C/HDL-C, Apo A2, B and C3 and Apo A1/Apo B levels between the stone and control
      groups (P > 0.05). Increased levels of serum LDL-C and Apo B and the LDL-C/HDL-C
      ratio (P < 0.05) were characterized as an index of cholesterol stones, while
      elevated levels of serum TG and Apo C2 (P < 0.05) as an index of pigment stones.
      CONCLUSIONS: Serum apolipoproteins might be more sensitive parameters as compared
      with serum lipids in distinguishing patients with stones from subjects without
      stones. There are different profiles of serum lipids and apolipoproteins in
      different chemical types of gallbladder stones.

PMID- 9594309
TI  - Experimental study on relationship between exogenous estrogen and breast cancer
      risk.
AB  - OBJECTIVE: To investigate the relationship between exogenous estrogen and breast
      cancer risk. METHODS: Female rats were randomly divided into three groups, namely
      diethylstilbestrol (DES), norethindrone compositae (CoNET) and control group. The
      histological structure and ultrastructural changes of mammae were observed. The
      levels of sexual hormones in serum were determined and the AgNOR counts, DNA
      contents and steroid receptor contents in mammary epithelium were also detected.
      RESULTS: In DES group, the level of progesterone (10.38 ng/ml) was obviously
      lower than that in the control group (13.37 ng/ml); the incidence of hyperplasia
      of mammary gland (73.33%) was significantly higher than that in the control group
      (7.69%); and the degree of hyperplasia was obviously more serious than that in
      the control group. Moreover, there were 13.33% of rats with atypical hyperplasia
      in DES group. The DNA contents, AgNOR counts and estrogen receptor (ER) positive
      rate were markedly higher in DES group (95.60, 2.43 and 71.71% respectively) than
      in the control group (83.07, 1.88 and 40% respectively). However, in CoNET group,
      there were no obvious influences on ER, AgNOR and DNA in mammary epithelium.
      CONCLUSIONS: Exogenous estrogen (DES) could affect the levels of sexual hormones
      in serum, accelerate the DNA duplication, increase the AgNOR counts and ER
      contents, and induce atypical hyperplasia and ultrastructural changes of mammary
      gland, hence becoming a latent risk factor of breast cancer. However, the results
      failed to suggest that the contraceptive, CoNET, could increase the risk of
      breast cancer.

PMID- 9594310
TI  - A comparative study on morphology and immunohistochemistry of rhabdomyosarcoma
      and embryonal skeletal muscles.
AB  - OBJECTIVE: To investigate the histologic and histogenetic relationship between
      various types of rhabdomyosarcomas (RMS) and embryonal skeletal muscle (ESM) for
      further understanding of the histogenesis, classification and pattern of
      differentiation of RMS. METHODS: Fifty cases of variant types of RMS and 20 cases
      of ESM at different gestational ages were available. All specimens were stained
      with HE, PAS, Van Gieson, Masson, phosphotungstic acid hematoxilin and with
      antibodies for the demonstration of vimentin, desmin, HHF-35 and myoglobin by ABC
      method. RESULTS: The results showed that the order of positive expression and the
      intensity of positive reaction of the different immunohistochemical staining were
      consistent with the degree of differentiation of the tumor and the development of
      the ESM. It is obvious that each type of RMS is composed of tumor cells in
      different degree of differentiation and is derived from primitive mesodermal
      cells which are capable of potential differentiation towards mature skeletal
      muscles. CONCLUSIONS: Based on the results of this study, an ideal histologic
      classification of RMS should reflect not only the cell morphology and histologic
      structures but also the degree of differentiation of the tumor cells.

PMID- 9594312
TI  - In commemoration of the one hundred and tenth anniversary of the Chinese Medical
      Journal.

PMID- 9594311
TI  - Human cytomegalovirus matrix protein PP150 is efficiently presented as one of
      target antigens for cytotoxic T lymphocyte recognition.
AB  - OBJECTIVE: To determine whether human cytomegalovirus (CMV) matrix protein PP150
      is efficiently presented for CMV-specific CTL recognition. METHODS: Recombinant
      vaccinia virus (Vac. PP150) encoding human CMV structural matrix protein PP150
      was constructed with vaccinia vector PSC11 and it was used to stimulate
      peripheral blond mononuclear cells from 5 CMV seropositive individuals. RESULTS:
      PP150-specific CTLs could be generated in all of them, which not only lysed Vac.
      PP150-infected fibroblasts, but also lysed CMV-infected targets. In the presence
      of RNA synthesis inhibitor Actinomycin D (Act D) or at very early stage of
      infection, PP150-specific CTL lysed CMV-infected targets as efficiently as in the
      absence of Act D or at late stage of infection. CONCLUSIONS: PP150 exogenously
      introduced with the virus infection could be efficiently presented prior to viral
      DNA replication and PP150 is one of the major target antigens for CTL
      recognition.

PMID- 9594313
TI  - Hypertension studies: Chinese experiences 1958-1996.

PMID- 9594314
TI  - Trends in steroid contraceptive research.

PMID- 9594315
TI  - Advances in the pathogenesis of atherosclerosis.

PMID- 9594316
TI  - Progress of cancer research in China.

PMID- 9594317
TI  - Calcium channel blockage and anti-free-radical actions of ginsenosides.

PMID- 9594318
TI  - The relationship between gut-derived endotoxemia and tumor necrosis factor,
      neopterin: experimental and clinical studies.
AB  - OBJECTIVE: To determine the relationship between gut-derived endotoxemia and
      tumor necrosis factor (TNF), neopterin/biopterin formation following hemorrhage,
      trauma and burns. METHODS: Rats were subjected to hemorrhagic shock (30 mmHg, 90
      180 min) and 40% III degrees thermal injury. Circulating endotoxin, TNF,
      biopterin levels and liver TNF mRNA expression were measured in animals following
      acute insults. Also, the subjects of this study included 35 patients with burn
      size greater than 30%, and 25 patients with multiple injuries (n = 18) and major
      surgery (n = 7). RESULTS: It was found that significant portal and systemic
      endotoxemia took place in the control animal after hemorrhagic shock and thermal
      injury, but almost not in the animals that treated by measures aiming at
      controlling endotoxin/bacteria translocation, including polymyxin B, monoclonal
      antibody against core lipopolysaccharide, and selective decontamination of the
      digestive tract (SDD). Concomitantly, hemorrhage and thermal injury resulted in
      significant increases in systemic plasma TNF level together with tissue TNF mRNA
      expression, which were associated with the initial appearance of endotoxin in
      portal vein. However, anti-endotoxin treatment markedly decreased circulating TNF
      level as well as peak TNF mRNA expression caused by acute insults. There were
      also lower serum biopterin values in the SDD-treated group as compared with the
      control group on day 5 postburn. On the other hand, the results showed that the
      amounts of plasma endotoxin in patients increased during the early stages
      following major burns, which was significantly correlated with plasma TNF levels,
      particularly in patients who developed sepsis and multiple organ failure.
      Although the presence of early endotoxemia did not influence the alterations in
      serum neopterin, patients with endotoxemia had much higher neopterin values than
      those who showed no endotoxemia from the second week onward. CONCLUSION: These
      results suggest that gut-derived endotoxemia could account, at least in part, for
      the inflammatory mediators formation and release, which might be involved in the
      pathogenesis of sepsis and multiple organ dysfunction following severe
      hemorrhage, trauma and burns.

PMID- 9594319
TI  - Abortion and emergency contraception: Chinese experience.

PMID- 9594320
TI  - Clinical study on the thrombolytic effect with different doses of urokinase in
      acute myocardial infarction. The Collaborative Research Group on Thrombolysis.
AB  - OBJECTIVE: To investigate the effects of different doses of intravenous domestic
      urokinase. METHODS: One thousand and twenty three cases of acute myocardial
      infarction within 6 hours after acute onset were divided randomly into two groups
      with 539 cases in the low dose group (urokinase 22,000IU/kg, total dose not lower
      than 1.2 million) and 484 in the high dose group (30,000IU/kg, total dose not
      more than 2.4 million). The patency of infarct-related coronary artery was
      assessed by uniform clinical criteria. RESULTS: In the low and high dose groups
      the patency rates were 67.3% and 67.8% respectively (P > 0.05); 4-week
      mortalities were 9.5% and 8.7% respectively (P > 0.05). Frequency of severe
      complications had no statistically significant difference between the two groups.
      Adverse bleeding was a little more frequent in the high than in the low dose
      group, and fatal cerebral hemorrhage in 2 cases occurred in the high dose group.
      CONCLUSION: Low dose urokinase, 22,000 IU per kg body weight with a total dose
      not lower than 1.2 million IU, is not only equally effective as high dose but
      also safer.

PMID- 9594321
TI  - Influence of different start time of urokinase therapy after acute myocardial
      infarction efficacy of thrombolysis. The Collaborative Research Group on
      Thrombolysis.
AB  - OBJECTIVE: To investigate the influence of different starting time of intravenous
      urokinase after onset of acute myocardial infarction on the efficacy of
      thrombolysis. METHODS: One thousand one hundred and thirty eight cases of acute
      myocardial infarction admitted in 37 collaborative hospitals were given
      intravenous urokinase with a standard program. Patency of infarct-related
      coronary artery was assessed by uniform clinical criteria. Patency rate and 4
      week mortality in groups of different starting time of urokinase administration
      after acute onset were compared. RESULTS: According to the starting time of
      urokinase administration after acute onset, the 1138 cases were divided into 4
      groups: 128 cases were within 2 hours (H), 461 Within 2-4h, 434 within 4-6h and
      115 within 6-12h. The patency rates were 71.9%, 70.1%, 63.6% and 40.0%,
      respectively and 4-week mortalities were 7.0%, 6.5%, 12.2% and 13.9%,
      respectively in the four groups. The difference of patency rates and 4-week week
      mortalities between the groups within 2 hours and within 2-4 hours were not
      statistically significant, so these two groups were combined into one, i.e.
      within 4 hours. The patency rate of the group within 4 hours (70.5%) was
      significantly higher than those of the groups within 4-6 hours (P < 0.025) and
      within 6-12 hours (P < 0.001); the 4-week mortality of the former (6.6%) was
      obviously lower than those of the latter two (all P < 0.01). The patency rate of
      the group within 4-6 hours was higher (P < 0.001), than that of the group within
      6-12 hours but the 4-week mortalities were not statistically different between
      the two groups. CONCLUSION: Intravenous urokinase starting within 4 hours after
      onset of acute myocardial infarction is of the best efficacy.

PMID- 9594322
TI  - Clinical trial of China-made recombinant streptokinase in acute myocardial
      infarction. Collaborative Study Group on Thrombolysis with China-made recombinant
      streptokinase.
AB  - OBJECTIVE: To evaluate the efficacy and safety of intravenous recombinant
      streptokinase (r-SK), produced in China, in the treatment of acute myocardial
      infarction (AMI). METHODS: One hundred and seventy-three patients with AMI
      admitted to seven hospitals from February to October 1995 were conformed to the
      inclusion and exclusion criteria of thrombolytic therapy. The patients were
      divided into two groups. One hundred and two patients in the Group A were
      randomized to receive r-SK (n = 51) or SK (n = 51). Seventy-one patients were
      treated with r-SK in the Group B. One and half million units of r-SK or SK were
      given intravenously over 60 minutes and the clinical criteria of reperfusion were
      evaluated. Coronary angiography was performed 90 minutes after thrombolytic
      therapy with r-SK in 34 patients and recanalization of infarct-related arteries
      was determined using the TIMI criteria. RESULTS: The reperfusion rate was 80.4%
      in 51 patients receiving r-SK and 74.5% in 51 patients receiving SK (P > 0. 05).
      The total reperfusion rate was 77.1% in 122 patients treated with r-SK. Ninety
      minutes after the initiation of thrombolytic therapy, the occluded infarct
      related arteries were patent in 70. 6% (24/34) of patients treated with r-SK.
      Chill, hypotension and mild bleeding occurred respectively in 4.1%, 5.7% and
      16.4% of patients with r-SK. CONCLUSION: China-made r-SK is a safe and effective
      thrombolytic agent.

PMID- 9594323
TI  - Effects of thrombolytic therapy on recanalization in different starting time of
      treatment after acute myocardial infarction.
AB  - OBJECTIVE: To investigate the effects of thrombolytic therapy on recanalization
      in different starting time of treatment after acute myocardial infarction.
      METHODS: 172 cases with intravenous thrombolytic agents were divided into 4
      groups: < or = 2 hours, > 2-4 hours, > 4-6 hours and > 6-12 hours, according to
      the different starting time of therapy after onset of symptoms. RESULTS: The
      recanalization rates were 78.6%, 74%, 39. 6% and 14.3% in < or = 2 hours, > 2-4
      hours, > 4-6 hours and > 6-12 hours, respectively. The recanalization rate within
      4 hours was significantly higher than those in the groups of > 4-6 hours AND > 6
      12 hours. The time interval from the initiation of thrombolytic therapy to
      reperfusion was increased as the starting time of thrombolysis after onset of
      symptoms was delayed. CONCLUSIONS: Starting time of thrombolysis within 4 hours
      after onset of acute myocardial infarction is of the best effect on
      recanalization.

PMID- 9594324
TI  - Percutaneous transluminal coronary angioplasty for acute myocardial infarction:
      initial experience in 43 cases.
AB  - OBJECTIVE: To evaluate the initial experience with the use of percutaneous
      transluminal coronary angioplasty (PTCA) in the set of acute myocardial
      infarction (AMI). METHODS: Between October 1993 and April 1996, PTCA was
      performed in 43 patients (34 male, 9 female) with initial onset of AMI. These
      patients ranged in age from 40 to 74 years (mean +/- SD, 60.3 3 +/- 9.2). Primary
      PTCA was performed in 16, rescue PTCA in 8, and semi-elective PTCA in 19
      patients. RESULTS: The initial success was achieved in 95.3% (41/ 43). Failed
      angioplasty occurred in 2 patients, with acute reocclusion after rescue PTCA
      (this patient died of cerebral stroke 3 days later) in one patient, and small
      local intimal dissection during semi-elective PTCA in another patient.
      CONCLUSION: PTCA was a safe and effective approach in the treatment of AMI in the
      present study patients, with a high primary success and low acute complication
      rate.

PMID- 9594325
TI  - A comparative study of intravenous accelerated streptokinase dose regimen with
      conventional dose regimen for coronary thrombolysis.

PMID- 9594326
TI  - Summary of national symposium on reperfusion treatment for acute myocardial
      infarction.

PMID- 9594327
TI  - Protective effects of salvianolic acid A against impairment of memory induced by
      cerebral ischemia-reperfusion in mice.
AB  - OBJECTIVE: To investigate the protective effects of Salvianolic acid A against
      impairment of memory induced by cerebral ischemia-reperfusion in mice and the
      relationship between antioxidant activity of salvianolic acid A and its
      protective effects on brain injury caused by reperfusion. METHODS: Step down and
      step through tests were used to examine the function of memory in the model of
      impairment of memory induced by cerebral ischemia-reperfusion in mice. RESULTS:
      Salvianolic acid A (Sal A) at the dosage of 3 and 10 mg.kg-1 i.v. could improve
      the impaired memory function induced by cerebral ischemia-reperfusion as shown in
      step down and step through tests. In step down tests, the mean number of errors
      of Sal A 3 and 10 mg.kg-1 treated group were 1.29, 1.15 and that of control group
      was 3.8 (P < 0.01). The latencies of these tests were longer than those of the
      control group. Meanwhile, 3 and 10 mg.kg of Sal A i.v. were found to reduce the
      malondialdehyde contents in the cortex, hippocampus and corpus striatum of
      cerebral ischemia-reperfusion rat in vivo. Sal A 10-100 nmol.L-1 was also shown
      to inhibit lipid-peroxidation of the brain and scavenge the free hydroxyl
      radicals in vitro. CONCLUSION: These indicate that the ameliorating effect of Sal
      A on learning and memory impairment caused by cerebral ischemia reperfusion may
      be related to its anti-oxidant activity.

PMID- 9594328
TI  - Radioimmunoimaging of arterial and venous thrombi in canine model using 99mTc
      labeled monoclonal antifibrin antibody.
AB  - OBJECTIVE: To evaluate the usefulness of 99mTc labelled monoclonal antifibrin
      antibody SZ-63 for the detection of vascular thrombi, and to investigate the
      feasibility of thrombus imaging 99mTc-SZ-63. METHODS: The monoclonal antibody SZ
      63 (Mab SZ-63), which reacts with D-dimer, XLFN and fibrin monomer was produced
      and labelled with 99mTc using pretinning procedure. After that, the femoral
      arterial or venous thrombus model was prepared in dogs and injected with 99mTc-SZ
      63 intravenously. Both arterial and venous thrombus models were imaged. RESULTS:
      Both the arterial and venous thrombi were clearly visible within 2.5 hours after
      injection of 99mTc-SZ-63. Quantitative imaging analysis showed that the ratios
      between the thrombus and the opposite vessel increased with time extension. The
      ratios of thrombus to blood or surrounding muscle were 2. 56 +/- 0.83 and 13.40
      +/- 5.10 for arterial thrombi and 3.34 +/- 1.06 and 22.40 +/- 6.40 for venous
      thrombi after the canines were killed. CONCLUSION: 99mTc-SZ-63 is a useful
      imaging agent for thrombus detection in vivo.

PMID- 9594329
TI  - Detection of minimal residual disease in leukemia using polymerase chain reaction
      and restriction analysis.
AB  - OBJECTIVE: To investigate the relationship between the clinical outcome of
      childhood acute lymphoblastic leukemia and the status of minimal residual disease
      after termination of therapy. METHODS: A total of 18 children with acute
      lymphoblastic leukemia were studied. Eleven cases were treated with chemotherapy,
      the other 7 with autologous peripheral blood stem cell transplantation (ABSCT) or
      autologous bone marrow transplantation (ABMT). The outcome of the 18 patients was
      obtained by clinical follow-up. Minimal residual disease was detected by means of
      the polymerase chain reaction (PCR) and restriction analysis. RESULTS: Minimal
      residual disease was detected in 9 patients after completion of therapy. Three
      out of the 9 patients relapsed within 3 to 6 months. Among the other 9 patients
      with no detectable minimal residual disease, no one relapsed. CONCLUSIONS: PCR
      detection of minimal residual disease after termination of therapy can identify
      patients at risk for relapse in future. Minimal residual disease that cannot be
      detected after termination of therapy may be one of the important factors for
      long-term disease-free survival.

PMID- 9594330
TI  - Detection of human papillomavirus DNA in condylomata acuminata treated with CO2
      laser by polymerase chain reaction.

PMID- 9594331
TI  - Changes in the prevalence of benign prostatic hyperplasia in China.
AB  - OBJECTIVE: To understand the rapid increase of benign prostatic hyperplasia (BPH)
      in China by a comparative study of the nutrition status and BPH morbidity between
      urban and rural areas. METHODS: A study was conducted in 1993-1995 in Beijing on
      the influence of diet on the prevalence of BPH in 413 rural and 419 urban male
      inhabitants over 40 years of age. RESULTS: The results indicated distinctive
      differences in dietary patterns and the prevalence of BPH between rural and urban
      inhabitants. CONCLUSION: The changing prevalence of BPH in China can be
      attributed to the increased daily intake of total calories, fat and animal
      protein, and the decreased daily intake of vegetables and whole grain, the
      sources of phytoestrogens.

PMID- 9594332
TI  - Establishment of doxorubicin-resistant human bladder cancer cell line (BUI
      87/ADMR) and its mechanism of multidrug resistance.
AB  - OBJECTIVE: To establish a doxorubicin-resistant human bladder cancer cell line,
      BIU-87/ADMR, and to study its biological characteristics and mechanism of drug
      resistance. METHODS: A human bladder cancer cell line resistant to doxorubicin,
      BIU-87/ADMR, has been established in vitro by exposing BIU-87 parent cells to
      progressively increasing concentrations of the drug over a period of 8 months.
      The cell line has been characterized in terms of growth kinetics, morphology,
      cross-resistance to other anticancerous agents, pharmacokinetics of daunorubicin
      and expression of P-glycoprotein (P-gp) which is closely related to the MDR
      phenotype. RESULTS: The BIU-87/ADMR cell line was 6.3 times more resistant to
      doxorubicin than the parent BIU-87. It exhibited cross-resistance to doxorubicin
      derivatives (epirubicin, daunorubicin), vincristine and etoposide, but not to
      cisplatin and mitomycin C. Compared to the parent cells, the resistant cells have
      a slower growth rate and lower confluent density. Unlike the parent BIU-87, about
      75% of the BIU-87/ADMR cells showed a positive reaction with monoclonal antibody
      against P-gp, JSB-1. Intracellular drug accumulation studies with fluorescence
      spectrometry indicated that the resistance exhibited by the BIU-87/ ADMR line was
      mainly caused by an increased active efflux. CONCLUSIONS: The results suggest
      that MDR is an important phenomenon in bladder cancer and that more than one
      pathway of MDR may be present in human bladder cancer cell lines. BIU-87/ADMR may
      be a useful model for the development of new chemotherapeutic strategies in
      overcoming drug-resistance in the treatment of bladder cancer.

PMID- 9594333
TI  - Action of autonomic drugs on the in vivo bladder base and proximal urethra in
      dog.
AB  - OBJECTIVE: To investigate the effects of autonomic drugs on the in vivo bladder
      base and proximal urethra in order to provide some reference materials for
      clinical usage of these drugs in the treatment of bladder outlet dysfunction.
      METHODS: In 35 dogs, the bladder base was separated from the bladder body and
      closed to constitute a small chamber. The changes of the pressure in the bladder
      base chamber and proximal urethra were recorded synchronously before and after
      administration of autonomic drugs. All data were analyzed with Student's t test.
      RESULTS: The bladder base had little response to acetylcholine (Ach) which
      however promoted a contraction of the proximal urethra. The effect of Ach on the
      proximal urethra was antagonized by phentolamine, but not by atropine.
      Isoprenaline resulted in relaxation of the bladder base, though it had little
      effect on the urethra. Norepinephrine (NE) produced contraction of the bladder
      base and urethra, while phentolamine caused a reduction in the bladder base and
      urethral pressure, and blocked the response of the bladder outlet region to NE.
      Angiotensin amide (AII) caused contraction of the bladder base and urethra, which
      was not obliterated by phentolamine. CONCLUSIONS: The cholinergic drug has no
      influence on the in vivo canine bladder base, but causes a contraction of the
      proximal urethra through indirect activation of alpha-receptors. The alpha
      adrenergic agents have great effects on the bladder base and urethra by acting on
      alpha-receptors within the musculature in the outlet region. The beta
      adrenoceptor agonist results in relaxation of the bladder base, but it has no
      effect on the urethra.

PMID- 9594335
TI  - Effect of TNF-alpha and IFN-alpha on the proliferation and cytotoxicity of
      lymphokine-activated killer cells in patients with bladder cancer.
AB  - OBJECTIVE: To investigate the effects of interleukin-2 (IL-2) combined with
      either tumor necrosis factor-alpha (TNF-alpha) or alpha-interferon (IFN-alpha) on
      the proliferation and cytolysis to bladder tumor cells of lymphokine-activated
      killer (LAK) cells in patients with bladder cancer. METHODS: LAK cells were
      generated by ficoll-paque density-centrifugation from 21 patients with bladder
      cancer and cultured in medium containing IL-2. LAK cell proliferation was assayed
      in the presence of various concentrations of either TNF-alpha or IFN-alpha by
      cell count in 96-well plates. Bladder cancer cell lines BIU-87 and EJ were
      cultured as target cells and the cytotoxicity of LAK cells was determined by 3
      (4,5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) assay. RESULTS:
      The proliferation of LAK cells induced by IL-2 was enhanced by TNF-alpha in a
      dose-responsive fashion. The direct growth support for the LAK cells was also
      observed with IFN-alpha at the concentration of 1000 U/ml after 48 hours of
      culture. TNF-alpha (5000 U/ml) resulted in an increase in the cytotoxicity of LAK
      cells to BIU-87 and EJ cells. However, the change of cytotoxicity of LAK cells
      treated with IFN-alpha was not statistically significant. CONCLUSIONS: TNF-alpha
      and IFN-alpha enhance the proliferation and activation of LAK cells and influence
      their antitumor cytotoxicity in patients with bladder cancer.

PMID- 9594334
TI  - Detection of chlamydia trachomatis by polymerase chain reaction assay in
      nonbacterial prostatitis.
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of polymerase chain
      reaction (PCR) technique in comparison with diethylaminoethyl-dextran (DEAE
      dextran)-treated HeLa cell culture method for detection of chlamydia trachomatis
      in nonbacterial prostatitis. METHODS: Thirty patients had symptoms of prostatitis
      for at least three months. None of them had evidence of urethritis on urethral
      Gram stain or recurrent bacteria. Routine localization of bacteria was negative.
      White blood cell count in expressed prostatic secretion (EPS) was more than 10
      per high-power field (10/HPF). None of these patients had received antibiotics
      during the six weeks before the study, although all had received multiple courses
      of antibiotics for treatment of prostatitis syndrome. The EPS specimens from
      these patients were placed in 0.5-ml Eppendorf tubes and stored at -70 degrees C
      until they were processed for PCR and DEAE-dextran-treated HeLa cell culture.
      RESULTS: Six specimens were positive for C. trachomatis by both PCR and culture,
      and 21 were negative by both tests. There were three specimens with discrepant
      results, including two that were positive by PCR and negative by culture, and one
      that was positive by culture and negative by PCR. Comparing PCR technique with
      culture method, the sensitivity, specificity, positive predictive value and
      negative predictive value of the former were 85.7%, 91.3%, 75.0% and 95.5%
      respectively. CONCLUSIONS: PCR analysis of EPS is a highly sensitive and specific
      noninvasive technique for detection of chlamydia trachomatis. It provides a
      unique opportunity for early identification of or rapid screening for chlamydia
      trachomatis infection in patients with nonbacterial prostatitis. The reliability
      of PCR assay offers clinicians a clear indication for the initiation of treatment
      of chlamydia trachomatis infection.

PMID- 9594336
TI  - Evaluation of the patency rate of infarct-related artery after intravenous
      urokinase in acute myocardial infarction by 90 minutes angiography. Collaborative
      Group of Clinical Trial for Urokinase Therapy.
AB  - OBJECTIVE: To evaluate the efficacy of intravenous (i.v.) thrombolytic therapy on
      acute myocardial infarction (AMI) and to evaluate the sensitivity and specificity
      of clinical criteria in deciding reperfusion rate by using 90 minutes angiography
      after initiation of the i.v. urokinase (UK). METHODS: Coronary artery angiography
      (CAG) was performed in 124 out of 1406 patients with AMI receiving i.v. UK (UKTP)
      (Guangdong Techpool Biochemical Pharmaceutical Co. Ltd. Guangzhou, China) from
      November 1994 to April 1996. 1.5 million units of UKTP were infused in 111
      patients, 2.0 million units in 10 patients and 1.0 million in 3 cases within 30
      minutes. CAG was performed 90 minutes after the initiation of thrombolytic
      therapy. RESULTS: Fifty-two patients had coronary flow grade of TI-MI-3 and 38
      patients TIMI-2 90 minutes after the onset of thrombolytic therapy. The total
      patency rate of infarct related artery (IRA) was 72.6%. There was no significant
      difference (P > 0.05) in the patency rate of IRA of various locations. The
      patency rate of LAD was 71.6% (53/74), of RCA was 71.4% (30/42), of LCX was 85.7%
      (6/7) and effective patency in one patient with left main artery occlusion.
      Although there was a tendency that the earlier the thrombolytic therapy, the
      higher the patency rate of IRA patency, the results did not meet the
      statistically significant level (P > 0.05). Using CAG as the gold standard, the
      clinical criteria used for evaluation of reperfusion rate had a sensitivity of
      88%, specificity of 69% and accuracy of 83% in prediction of the reperfusion of
      IRA. CONCLUSION: UK is effective and reliable in i.v. thrombolytic therapy of
      AMI. The clinical criteria used to predict reperfusion of IRA have a higher
      sensitivity and relatively lower specificity.

PMID- 9594337
TI  - Effects of patency of infarct-related coronary artery on acute outcome in acute
      myocardial infarction patients undergoing urokinase therapy. Collaborative
      Research Group on Thrombolysis.
AB  - OBJECTIVE: To study the effects of patency of infarct-related coronary artery on
      acute outcome in cases of acute myocardial infarction undergoing urokinase
      therapy. METHODS: One thousand one hundred and thirty-eight cases of acute
      myocardial infarction admitted in 37 collaborative hospitals were given urokinase
      intravenously with a standard program. Patency of infarct-related coronary artery
      assessed by uniform criteria occurred in 757 patients (66.5%) and non-patency in
      381 patients (33.5%). Four-week mortality and frequency of various severe
      complications were compared between patency patients and non-patency patients.
      RESULTS: The 4-week mortality in patients with patency was 3.4% versus 21.8% in
      those without patency (P < 0.001). Frequencies of various severe complications,
      such as heart failure, shock, ventricular fibrillation, bundle branch blocks and
      mechanical complications (P < 0.01), and complete atrioventricular block (P <
      0.05) were much higher in patients without than in those with patency. In large
      sized infarcts such as high lateral plus anterior wall infarction the difference
      in 4 week mortality was even more obvious between patients with and without
      patency (2.6% vs 32.7%, P < 0.001). Using Cox proportional hazards regression
      model analysis, patency of infarct-related coronary artery was defined as the
      most important independent predictor of 4-week mortality. The risk ratio for
      occluded versus patent infarct-related coronary artery was 6.69. CONCLUSION: On
      univariate and multivariate analyses, patency of the infarct-related coronary
      artery was the most important prognostic factor for acute outcome in acute
      myocardial infarction.

PMID- 9594338
TI  - Long-term prognosis of patency of infarct-related coronary artery after
      thrombolytic treatment in acute myocardial infarction. Collaborative Research
      Group on Thrombolysis.
AB  - OBJECTIVE: To investigate the long-term prognostic influence of patency of the
      infarct-related coronary artery. METHODS: One thousand two hundred and sixty
      seven cases of acute myocardial infarction with thrombolytic treatment between
      July 1991 and January 1995 in 36 collaborative hospitals were followed-up after
      discharge with a total follow-up rate of 84.5%. Patency of infarct-related
      coronary artery was assessed by uniform clinical criteria. Eight hundred and
      forty three patients with patency were followed up for 16.0 +/- 10.4 months and
      424 patients without patency for 19.2 +/- 12.22. Death or up to the end of March,
      1995 was used as the end point. RESULTS: Comparisons of patients with patent
      versus nonpatent infarct-related coronary artery during follow-up showed: (1)
      Cardiac death rate was 2.85% in patients with patency while 4.72% in those
      without patency (logrank test, P > 0.1). (2) Three-year survival rates calculated
      by Kaplan-Meier curve were 91.6% and 73.9% respectively (logrank test, P <
      0.001). (3) Incidence of reinfarction were 5.7% and 5.9% respectively (P < 0.05).
      (4) Patients with class III-IV NYHA cardiac function occurred in 11.3% and 17.9%
      respectively (P < 0.01). (5) By Cox regression model analysis patency of infarct
      related coronary artery, recurrent infarction, age and infarct sites were
      independent prognostic factors. Survival probability increased by 33.5% in
      patients with patency compared to those without patency. CONCLUSION: It is
      evident that patency of infarct-related coronary artery could improve long-term
      survival.

PMID- 9594339
TI  - Manifestation of Behcet's disease in the digestive tract.
AB  - OBJECTIVE: To study the manifestations of Behcet's disease (BD) in the digestive
      tract and its differential diagnosis from common inflammatory bowel diseases.
      METHODS: The symptoms and endoscopic, X-ray's or surgical characteristics of 24
      cases of Behcet's disease with digestive tract manifestations were analysed.
      RESULTS: The lesions mainly occurred in tileocecum, and frequently led to
      hemorrhage that required surgery. The recurrent rate was as high as 77.7%.
      CONCLUSION: Importance should be attached to early diagnosis of BD of the
      digestive tract to prevent serious complications.

PMID- 9594340
TI  - Clinical significance of serum 7S collagen and type VI collagen levels for the
      diagnosis of hepatic fibrosis.
AB  - OBJECTIVE: To measure serum 7S collagen (7S-C) and type VI collagen (VI-C) levels
      by radioimmunoassay (RIA) in Chinese patients with various liver disorders and in
      CCl4-treated SD rats, and to investigate the significance of the elevated levels
      of serum 7S-C and VI-C. METHODS: Serum 7S-C and VI-C levels were measured in 40
      healthy control subjects, 168 patients with various liver disorders and non
      hepatic diseases, and 52 CCl4-treated SD rats by using RIA which was developed in
      our hospital. RESULTS: Serum 7S-C and VI-C were significantly elevated in
      patients with chronic active hepatitis (CAH), liver cirrhosis (LC), hepatic
      cellular carcinoma (HCC) (P < 0.01 respectively), chronic persistent hepatitis
      (CPH), and some with non-hepatic diseases (P < 0.05). Serum 7S-C, serum laminin
      and hyaluronic acid were well correlated. Serum 7S-C and VI-C were not closely
      correlated. Both collagens were correlated with serum albumin/globulin ratio,
      aminotransferase and total bilirubin, not with alkaline phosphatase. In CCl4
      treated SD rats, serum 7S collagen and type VI collagen levels were correlated
      with the degree of hepatic fibrosis. CONCLUSIONS: Serum 7S collagen and type VI
      collagen are useful markers for diagnosing liver fibrosis. And the combined
      measurement of IV-C, VI-C and other markers of connective tissue metabolism or
      biochemical data seems to provide additional information to predict progressive
      hepatic fibrosis.

PMID- 9594341
TI  - Clinical significance of the immunohistochemical detection of p53 protein in
      endoscopic biopsy specimens.
AB  - OBJECTIVE: To evaluate the utility of immunohistochemical staining of p53
      expression in endoscopic biopsy specimens in clinical practice. METHODS: Using a
      streptavidin-peroxidase (S-P) conjugate method with monoclonal p53 antibody Do-7,
      the expression of p53 was investigated immunohistochemically in 150 endoscopic
      biopsies and paired brushings from patients with benign and malignant gastric
      diseases. Among them, 22 cases with gastric carcinoma underwent the gastrectomy
      and the immunohistochemistry was repeated in the resected cancerous tissues of
      the same patient. RESULTS: p53 expression in endoscopic specimens was detectable
      in 35.7% cases of gastric carcinoma (n = 70), 5.9% of gastric polyps (n = 17),
      16.7% of gastric mucosal dysplasia (n = 18) and 4.0% of chronic atrophic
      gastritis (n = 25), but no protein expression was observed in cases of chronic
      active gastritis (n = 20). In 22 patients with tumor resection, 8 (36.4%) were
      identified with p53 expression in endoscopic specimens before surgery, while 10
      (45.5%) were identified with the same expression in surgical specimens, the real
      positive rate was 80.0%, no false positives were observed in endoscopic
      specimens. Furthermore, p53 expression in gastric carcinoma was closely
      correlated with clinical stage and lymph nodes involvement, but did not correlate
      with histologic type. CONCLUSIONS: Assay of p53 by immunohistochemistry in
      endoscopic biopsy specimens and brushings is an easy and reliable technique to
      assess p53 status in gastric carcinoma, and thus could serve as a marker to
      foresee the prognosis in these patients and assist in the diagnosis of malignancy
      before surgery. It may also be a valuable marker in screening patients with high
      risk of gastric carcinoma.

PMID- 9594343
TI  - Investigation of attitudes towards organ transplantation in young people in
      China.
AB  - OBJECTIVE: To investigate the attitudes toward organ transplantation, organ
      donation and recipients in young people in Beijing, Shanghai, and Wuhan. METHODS:
      A questionnaire was designed for 3012 young people aged 20-45 years (999 in
      Beijing, 990 in Shanghai, and 1023 in Wuhan). The data of questionnaire were
      processed with SPSS software. RESULTS: Over 90% of the respondents knew that
      human organs can be transplanted; over 85% considered that organ transplantation
      is a welfare undertaking; more than 85% thought that when someone's organ is in
      critical condition, it is necessary to perform organ transplantation; over 70%
      expressed willingness to receive organ transplantation if it is needed or
      possible. In the mode of organ donation, 70% emphasized that organ donation
      should be dependent on volunteers and the donor should be rewarded in a certain
      form. Organ recipients in sequence are relatives, specialized medical
      institutions, friends, members of volunteer organizations, and others. The
      factors affecting the attitudes towards organ transplantation are analyzed.
      CONCLUSION: There is a better attitude toward organ transplantation among young
      people in cities. The conventional attitudes and feudal habits are one of the
      major obstacles to the course of organ donation in China.

PMID- 9594342
TI  - Effects of methylprednisolone and cyclophosphamide pulse therapy on renal
      infiltrating cells in patients with crescentic glomerulonephritis.
AB  - OBJECTIVE: To investigate the effects of pulse methylprednisolone (MP) and
      monthly intravenous cyclophosphamide (CTX) therapy (MP + CTX) on renal
      infiltrating cells in patients with rapid progressive glomerular nephritis
      (RPGN). METHODS: Twelve patients with RPGN (> 50% crescents) were given MP + CTX
      therapy and received repeated renal biopsies within 4 to 12 weeks after MP + CTX
      treatment. Seven were diagnosed as type II RPGN, including one case of IgA
      nephropathy, 2 cases of idiopathic RPGN and 4 cases of lupus nephritis and five
      were diagnosed as type III RPGN, including 2 cases of idiopathic RPGN and 3 cases
      of vasculitis. The changes of infiltrating CD4+, CD8+, CD68+ and proliferating
      cell nuclear antigen-PCNA+ cell levels were determined by four PAP method in
      glomeruli and interstitium. RESULTS: In the patients before MP + CTX therapy,
      there were higher levels of infiltrating CD4+ and CD8+ cells (306 +/- 118 and 223
      +/- 98.4Num/mm2) in renal interstitium, CD68+ cells (17.2 +/- 9.95 Num/G) in
      glomeruli and (1120 +/- 229 Num/mm2) in interstitium, and PCNA+ cells (7.56 +/-
      3.57 Num/G) in glomeruli and (17.6 +/- 6.85 Num/mm2) in interstitium as compared
      with those in the patients after MP + CTX therapy (CD4+/CD8+ cells were 171 +/-
      87.5/121 +/- 38.4 Num/mm2, CD68+ cells were 9.04 +/- 4.33 Num/G and 600 +/- 107
      Num/mm2, and PCNA+ cells were 2.04 +/- 1.43 Num/G and 9.40 +/- 4.45 Num/mm2).
      These changes were associated with improving renal dysfunctions (the levels of
      serum creatinine and proteinuria decreased gradually from 766 +/- 356 to 284 +/-
      192 mumol/L and 2.60 +/- 1.46 to 1.29 +/- 0.85 g/day). CONCLUSIONS: Our data
      indicate that the renal infiltrating cells may play an important role in renal
      injury in patients with RPGN. The effects of MP + CTX therapy on improving renal
      dysfunctions may partially contribute to its amelioration of infiltrating cells
      in renal tissues. The degrees of CD4+, CD68+, and PCNA+ cells in the kidney may
      be useful indicators of MP + CTX therapy for RPGN.

PMID- 9594344
TI  - Transfer of a branch of the anterior interosseus nerve to the motor branch of the
      median nerve and ulnar nerve.
AB  - OBJECTIVE: To explore the applied microsurgical anatomy of the intrinsic hand
      muscles and related nerves after nerve injuries in the wrist region and to report
      the results of new technique for the restoration of motor functions of the
      injured nerves. METHODS: Seven fresh forearm amputation specimens were employed
      for studying the anatomical and microsurgical characteristics of the relevant
      tissues. Transfer of the pronator quadratus branch of the anterior interosseous
      nerve (PBAN) to the recurrent branch of the median nerve (RBMN) and the deep
      branch of the ulnar nerve (DBUN) to restore the functions of the intrinsic hand
      muscles was performed on 20 patients from April 1979 to January 1994. Fourteen
      patients were followed up for 3-9 years with an average of 5 years and 8 months.
      RESULTS: The RBMN, DBUN and PBAN had approximately the same lengths of diameter
      and similar amounts of fascicles and nerve fibers so that after nerve transfer,
      the possibilities of misdirected connections were greatly reduced. In the latest
      follow-up, normal muscle strength was regained in 3 patients, grade VI strength
      in 6, grade III strength in 3 and grade II strength in 2. CONCLUSION: This new
      technique is able to restore the intrinsic hand muscular functions after median
      or ulnar nerve injuries in the wrist region or distal forearm.

PMID- 9594345
TI  - A biomechanical study of fast throwing movements of the shoulder in baseball
      pitching.
AB  - OBJECTIVE: To define the biomechanic function of the shoulder in fast throwing
      movements in baseball pitching. METHODS: Using NAC high-speed video and PIAS LA
      555 computer system, overhand pitching movements carried out by 12 healthy
      Japanese professional baseball pitchers were analyzed in three dimensions. The
      pitching motion was displayed as stick to sick figures dynamically. RESULTS:
      Pitching motion was a combination of translational and rotational movements.
      Acceleration and deceleration, being two typical motion patterns, worked
      sequentially through the anatomic link system from the pivot leg to the pitching
      hand. During the acceleration phase, the shoulder joint acted as a junction point
      and a fulcrum, supporting the rotational acceleration motion, shoulder forward
      flexion and elbow extension. According to the changing glenohumeral angles of the
      pitching shoulder, shearing force turned into tension force which worked on the
      anterior shoulder structures and then shifted to the posterior part of the joint.
      CONCLUSIONS: In fast throwing motion, the shoulder functions as an important
      fulcrum to support the pitching arm during the acceleration phase. Avoiding
      excessive stress and shearing force on the joint components and enhancing
      coordination of muscle action are important to a successful throwing motion and
      the prevention of shoulder injury.

PMID- 9594346
TI  - Familial occurrence of hemangioblastoma of central nervous system.
AB  - OBJECTIVE: To study the familial occurrence of hemangioblastoma of the central
      nervous system and to search for an effective way to diagnose and manage the
      disease. METHODS: From 1974 to 1993, six patients with hemangioblastoma with
      family history underwent surgical treatment at our hospital. Computerized
      tomography (CT) or magnetic resonance imaging (MRI) technique was used for the
      diagnoses before operation. RESULTS: Each patient had more than two relatives
      with hemangioblastoma. Multiple lesions were found in two of the six familial
      hemangioblastoma cases. All the patients recovered well after operation. So far,
      no victims have been discovered in the third generation. CONCLUSIONS: The high
      occurrence rate of familial hemangioblastoma cases suggests an involvement of
      hereditary factors. We need a long follow-up study on the descendants of familial
      hemangioblastoma patients. MRI is of diagnostic value in determining the location
      and nature of hemangioblastoma in both brain and spinal cord. A thorough
      examination is necessary for hemangioblastoma patients, and microsurgery is
      important in removing the tumor.

PMID- 9594348
TI  - Hemophilic pseudotumor involving maxilla and tibia.

PMID- 9594347
TI  - Detection of c-myc gene expression in nasopharyngeal carcinoma by nonradioactive
      in situ hybridization and immunohistochemistry.
AB  - OBJECTIVE: To investigate the c-myc gene expression in nasopharyngeal carcinoma
      (NPC) at mRNA and protein levels, and to evaluate the relationship between the
      degree of expression and the clinicopathological data. METHODS: The expression of
      c-myc specific mRNA and protein was detected using in situ hybridization with
      digoxigenin-labeled probe and immunohistochemistry in 12 cases of normal
      nasopharyngeal epithelium (NE) and 48 cases of NPC. The intensity of staining for
      each sample was assessed as negative, weak, moderate and intense. Statistical
      analyses were performed using the Chi square test and the rank sum test. RESULTS:
      For normal NE 41.7% (5/12) had weak (4/12) or moderate (1/12) staining for c-myc
      protein and 41.7% (5/12) had weak staining for c-myc mRNA. In contrast, 89.6%
      (43/48) of NPC showed some degree of c-myc protein positive and 87.5% (42/48)
      showed some degree of c-myc mRNA positive. In most samples, the expression of c
      myc protein was consistent with that of c-myc mRNA. C-myc protein and mRNA
      expression levels in NPC were significantly higher than those in normal NE, and
      correlated with early recurrence, but they were not significantly related to
      patient's age, sex, EBVCA-IgA titre, disease stage, lymph node status and
      metastasis. CONCLUSIONS: C-myc gene over-expression may be involved in the
      pathogenesis and early recurrence of NPC. Further studies are needed to
      substantiate the preliminary findings.

PMID- 9594349
TI  - Disability among the elderly in China: analysis of the national sampling survey
      of disability in 1987.

PMID- 9594350
TI  - Clinical and etiological study of painful ophthalmoplegia syndrome.

PMID- 9594351
TI  - The brain's way of dealing with its environment.

PMID- 9594352
TI  - The meaning and the message of biological integration.

PMID- 9594353
TI  - Is the heart preadapted to hypoxia? Evidence from fractal dynamics of heartbeat
      interval fluctuations at high altitude (5,050 m).
AB  - The dynamics of heartbeat interval time series over large time scales were
      studied by a modified random walk analysis introduced recently as Detrended
      Fluctuation Analysis. In this analysis, the intrinsic fractal long-range power
      law correlation properties of beat-to-beat fluctuations generated by the
      dynamical system (i.e., cardiac rhythm generator), after decomposition from
      extrinsic uncorrelated sources, can be quantified by the scaling exponent (alpha)
      which, in healthy subjects, for time scales of approximately 10(4) beats is
      approximately 1.0. The effects of chronic hypoxia were determined from serial
      heartbeat interval time series of digitized twenty-four-hour ambulatory ECGs
      recorded in nine healthy subjects (mean age thirty-four years old) at sea level
      and during a sojourn at 5,050 m for thirty-four days (EvK2-CNR Pyramid
      Laboratory, Sagarmatha National Park, Nepal). The group averaged alpha exponent
      (+/- SD) was 0.99 +/- 0.04 (range 0.93-1.04). Longitudinal assessment of alpha in
      individual subjects did not reveal any effect of exposure to chronic high
      altitude hypoxia. The finding of alpha approximately 1 indicating scale-invariant
      long-range power-law correlations (1/f noise) of heartbeat fluctuations would
      reflect a genuinely self-similar fractal process that typically generates
      fluctuations on a wide range of time scales. Lack of a characteristic time scale
      along with the absence of any effect from exposure to chronic hypoxia on scaling
      properties suggests that the neuroautonomic cardiac control system is preadapted
      to hypoxia which helps prevent excessive mode-locking (error tolerance) that
      would restrict its functional responsiveness (plasticity) to hypoxic or other
      physiological stimuli.

PMID- 9594354
TI  - Virtual information systems.

PMID- 9594355
TI  - Effect of nutritional supplements on attentional-deficit hyperactivity disorder.
AB  - This study reports the effects of two nutritional products upon the severity of
      symptoms in children with confirmed diagnoses of Attention-Deficit Hyperactivity
      Disorder (ADHD): a glyconutritional product containing saccharides known to be
      important in healthy functioning and a phytonutritional product containing flash
      dried fruits and vegetables. Seventeen ADHD children were recruited from a local
      parent support group. Parents of five of the subjects did not have their children
      on methylphenidate. Of the remaining twelve, all on methylphenidate, six were
      left on prescribed doses (random assignment). The other six had their doses
      reduced by half after two weeks (study duration was six weeks). The subjects were
      assessed initially and three subsequent times over a period of six weeks
      (longitudinal nonrandomized design). The behavior disorder items for ADHD,
      Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD) as listed in the
      Diagnostic and Statistical Manual for Mental Disorders (DSM IV) (American
      Psychiatric Association, 1994) were rated by teachers and parents on a 3-point
      scale. Also included was a Side Effects Scale described by Barkley (1990). The
      children received the glyconutritional supplement for the entire six weeks. After
      three weeks, the phytonutritional supplement was added to the diet to increase
      the probability of positive results. The glyconutritional supplement decreased
      the number and severity of ADHD, associated ODD and CD symptoms, and side effects
      in all groups during the first two weeks of the study. There was little further
      reduction with the addition of the phytonutritional supplement. The three study
      groups did not differ statistically in degree of reduction over observations.
      Present results suggest that symptoms of ADHD may be reduced by the addition to
      the diet of saccharides used by the body in glycoconjugate synthesis.

PMID- 9594356
TI  - The effects of nutritional supplements on the symptoms of fibromyalgia and
      chronic fatigue syndrome.
AB  - This article reports the results of a within-subject design. Fifty subjects with
      a physician diagnosis of fibromyalgia (FM) and/or chronic fatigue syndrome (CFS)
      were interviewed using a structured interview from. Each subject was interviewed
      initially, and again nine months later (follow-up). Subjects had, on their own,
      consumed nutritional supplements including freeze-dried aloe vera gel extract; a
      combination of freeze-dried aloe vera gel extract and additional plant-derived
      saccharides; freeze-dried fruits and vegetables in combination with the
      saccharides; and a formulation of dioscorea complex containing the saccharides
      and a vitamin/mineral complex. With medical treatments, approximately 25 percent
      of FM patients improve, but the beneficial effects of medical treatment rarely
      persist more than a few months. All subjects in this study had received some form
      of medical treatment prior to taking the nutritional supplements, but none with
      enduring success. Nutritional supplements resulted in a remarkable reduction in
      initial symptom severity, with continued improvement in the period between
      initial assessment and the follow-up. Further research is needed to verify these
      results, specifically crossover designs in well-defined populations.

PMID- 9594357
TI  - Use of reticulocyte cellular indices in the diagnosis and treatment of
      hematological disorders.
AB  - Automated counting of reticulocytes has markedly increased the precision and
      accuracy of this assay compared with the traditional manual counts. In addition,
      several new reticulocyte parameters are now available to clinicians and
      pathologists. This review examines the potential role of these parameters in the
      diagnosis and management of anemias. Reticulocyte maturity can now be assessed
      based on the staining intensity of reticulocytes, which is proportional to their
      RNA content. However, the clinical value of the numerical estimate of the
      immature reticulocyte fraction has not been yet demonstrated. In the bone marrow
      transplant setting, there is no clear evidence that the use of this index results
      in improved care of these patients, and many studies have failed to show its
      superiority compared with the traditional white cell count, especially for
      autologous transplants. Direct measurement of reticulocyte volume, hemoglobin
      concentration, and hemoglobin content are now available. Studies have shown that
      these parameters, and hemoglobin content in particular, allow a real-time
      assessment of the functional state of the erythroid marrow. In the setting of
      recombinant human erythropoietin therapy, studies of hemoglobin content have
      shown that this index allows an early detection of functional iron deficiency.
      Preliminary studies have also shown that this index may be helpful in the
      diagnosis of iron deficiency and in the monitoring of iron replacement therapy.

PMID- 9594358
TI  - Immunopharmacology of human mast cells and basophils.
AB  - Human mast cells and basophils play a key role in the pathogenesis of several
      immunological and inflammatory disorders, not only by producing inflammatory and
      fibrogenic mediators, but also by directly (CD40 ligand) and indirectly secreting
      various cytokines and chemokines. Studies carried out to evaluate the effects of
      drugs that modulate the release of mediators and cytokines from these cells have
      contributed to clarifying the biochemical mechanism by which immunological and
      non-immunological stimuli activate these cells. Significant differences have been
      documented between human mast cells and basophils as regard the pharmacological
      agents that modulate the release of mediators, between mast cells isolated from
      different anatomical sites, and between compounds of the same class of drugs.
      Efforts to gain insight into the biochemical events occurring during
      immunological activation of mast cells and basophils could lead to the
      identification of new biochemical targets for therapeutic interventions in
      several immunological disorders.

PMID- 9594359
TI  - Different pattern of cytokine production and mRNA expression by lymphoid and non
      lymphoid cells isolated from human palatine tonsil.
AB  - To investigate the cytokines involved in the interaction between circulating (B
      and T lymphocytes) and non-circulating (stromal cells) elements present in
      lymphoid tissue, highly purified populations were isolated from human tonsils and
      the cytokine production and mRNA expression (interleukin-1 alpha, -2, -4, -5, -6,
      -8, -10, leukocyte inhibitory factor, granulocyte-macrophage colony-stimulating
      factor, and interferon-gamma) were assessed both by immunoassay and reverse
      transcriptase polymerase chain reaction under resting conditions and after
      activation with tumor necrosis factor-alpha. Under basal conditions most
      cytokines were not detected, except for interleukin-8 which was produced by T
      lymphocytes and lymphoid cells. Activation by tumor necrosis factor-alpha induced
      interleukin-8 production by B lymphocytes. Tonsillar T lymphocytes expressed mRNA
      for interleukin-1 alpha, -8, -10, -4, leukocyte inhibitory factor, and interferon
      gamma, only interleukin-4 was expressed by resting peripheral blood T
      lymphocytes. Tonsillar B lymphocytes were mRNA positive for interleukin-1 alpha, 
      8, -10, leukocyte inhibitory factor, and interferon-gamma, these were not
      expressed by peripheral blood B lymphocytes. Stromal cells constitutively produce
      interleukin-6 whose levels increased 5 times upon tumor necrosis factor-alpha
      activation Granulocyte-macrophage colony-stimulating factor and interleukin-8
      were detected only after tumor necrosis factor-alpha activation. Only stromal
      cells constitutively express interleukin-6 and granulocyte-macrophage colony
      stimulating factor and show a cytokine pattern different from that described for
      other non-lymphoid cells, such as follicular dendritic cells. These data indicate
      that in the human tonsil population, lymphoid and non-lymphoid cells can be
      distinguished by different patterns of cytokine expression.

PMID- 9594360
TI  - Determination of antibodies to extractable nuclear antigens by commercial kits: a
      multicenter study.
AB  - Several enzyme immunoassays for serum antibodies to extractable nuclear antigen
      have recently become available. The aim of this study was to evaluate the results
      obtained with: (1) the same kit under different conditions; (2) different enzyme
      immunoassays; (3) Western blot and enzyme immunoassays. Twenty-five sera from
      patients with autoimmune disorders were tested in five different laboratories by
      one Western blot and four enzyme immunoassay commercial kits. The different
      methods produced comparable qualitative results. However, semiquantitative
      evaluation, based on a cut-off value (index), yielded different results due both
      to laboratory conditions and to the kits employed. Standardization of commercial
      products and methods should be improved so that the results of different
      laboratories can be compared and large-scale and follow-up studies conducted.
      Western blot analysis could also be useful to analyze complex reactivities,
      although greater experience is necessary to interpret these results correctly.

PMID- 9594361
TI  - Alterations of cerebral blood flow and antiphospholipid antibodies in patients
      with systemic lupus erythematosus.
AB  - Twenty-two patients with systemic lupus erythematosus and 13 healthy controls
      were included in a cerebral blood flow study and underwent brain-dedicated single
      photon emission computed tomography using 99m technetium-d, l-hexamethylpropylene
      amine oxime together with a brain computed tomography scan. Plasma levels of
      antiphospholipid antibodies (lupus anticoagulant and anticardiolipin IgM and IgG
      antibodies) were also determined. Brain computed tomography showed signs of focal
      cerebral ischemia in 4 patients (18%), whereas cerebral blood flow by single
      photon emission computed tomography was abnormal in 13 of 22 patients (59%), who
      showed bilateral or monolateral hypoperfusion in the temporo-parietal regions.
      Patients with abnormal cerebral blood flow had a longer duration of disease than
      those with normal blood flow (8.9 +/- 1.9 years vs. 5.3 +/- 1.5 years, P < 0.05).
      Plasma antiphospholipid antibodies were present in 15 patients (68%), but the
      prevalence was similar in those with normal (6/9, 66%), or abnormal (9/13, 69%)
      cerebral blood flow. No statistically significant difference in lupus
      anticoagulant or anticardiolipin antibodies was observed between patients with
      and without cerebral blood flow abnormalities. Our study shows that patients with
      systemic lupus erythematosus frequently have cerebral blood flow abnormalities,
      which could precede those observed by computed tomography. Plasma lupus
      anticoagulant and anticardiolipin titers were not correlated with normal cerebral
      blood flow.

PMID- 9594363
TI  - Primary ex vivo culture of keratinocytes isolated from hypertrophic scars as a
      means of biochemical characterization of CD36.
AB  - The CD36 antigen is a molecule which is ectopically expressed on epidermal
      keratinocytes of hypertrophic scars and is a good candidate for a marker for a
      broad range of skin pathologies. Most marker studies have been performed using
      immunohistochemical techniques on fixed skin sections. Our aim was to investigate
      the biochemical features of the CD36 expressed in pathological keratinocytes and
      to find an in vitro model for the study of the regulation of its expression. Here
      we show how keratinocytes isolated from hypertrophic scars can be cultivated in
      vitro and employed as a model for the study of these cells. We demonstrated that
      the antigenic features of the CD36 expressed on keratinocytes of hypertrophic
      scars are identical to those described for the CD36 expressed by other cell
      types. The molecule was expressed on the surface of keratinocytes which were non
      adherent in vitro. Adherent and proliferating keratinocytes, as well as normal
      keratinocytes, were CD36 negative both at the surface and intracellularly. The in
      vitro proliferating cells from hypertrophic scars, but not the normal
      keratinocytes, showed intracellular expression of CD36 after long-term culture
      and cell stratification, suggesting a regulated expression of CD36 in
      pathological keratinocyte differentiation.

PMID- 9594362
TI  - Lipoprotein disorder in brain infarction and hemorrhage.
AB  - The cholesterol, triglyceride, and apolipoprotein B content of very low-,
      intermediate-, low-, and high-density lipoprotein fractions (separated by
      ultracentrifugation) and plasma were measured in healthy controls and patients
      with atherothrombotic infarction (26), lacunar infarction (26), and brain
      hemorrhage (14). In both atherothrombotic and lacunar infarction, increased
      plasma and low-density lipoprotein apolipoprotein B and a decreased low-density
      lipoprotein cholesterol/apolipoprotein B ratio were noted. In brain hemorrhage
      patients, a decreased ratio was also observed. These findings suggest that
      increased small dense low-density lipoprotein is a characteristic risk factor for
      atherothrombotic and lacunar infarction.

PMID- 9594364
TI  - Human lymphoblastoid cells produce extracellular matrix-degrading enzymes and
      induce endothelial cell proliferation, migration, morphogenesis, and
      angiogenesis.
AB  - Human lymphoproliferative diseases can be hypothesized to invade locally and to
      metastatize via mechanisms similar to those developed by a variety of solid
      tumors, i.e., the secretion of extracellular matrix-degrading enzymes and
      stimulation of angiogenesis. To assess this hypothesis, Namalwa, Raji, and Daudi
      cell lines (Burkitt's lymphoma), LIK and SB cell lines (B-cell lymphoblastic
      leukemia), CEM and Jurkat cell lines (T-cell lymphoblastic leukemia), and U266
      cell line (multiple myeloma) were evaluated for their capacity to produce matrix
      metalloproteinase-2 and -9, and urokinase-type plasminogen activator. These cell
      lines were also assessed for their ability: (1) to produce the angiogenic basic
      fibroblast growth factor and vascular endothelial growth factor; (2) to induce an
      angiogenic phenotype in cultured endothelial cells, represented by cell
      proliferation, chemotaxis, and morphogenesis; (3) to stimulate angiogenesis in
      different in vivo experimental models. All cell lines expressed the mRNA for one
      or both metalloproteinases. Namalwa, Raji, LIK, SB, and U266 cells secreted the
      active form of both metalloproteinases, while Daudi, CEM, and Jurkat cells
      produced metalloproteinase-2 but not-9. In contrast, urokinase-type plasminogen
      activator was secreted only by SB cells. While Raji, LIK, SB, CEM, and Jurkat
      cells secreted both basic fibroblast growth factor and vascular endothelial
      growth factor, Daudi and U266 cells produced only the former, and Namalwa cells
      only the latter. Accordingly, the conditioned medium of all cell lines stimulated
      cell proliferation and/or chemotaxis in cultured endothelial cells, with the
      exception of that of Namalwa cells which was ineffective. The conditioned medium
      of CEM and Jurkat cells induced morphogenesis in cultured endothelial cells grown
      on a reconstituted basement membrane (Matrigel). Lastly, Namalwa, Raji, LIK, SB,
      U266, CEM, and Jurkat cells induced angiogenesis and mononuclear cell recruitment
      in the murine Matrigel sponge model and in a chick embryo chorioallantoic
      membrane assay. The extent of angiogenesis in both models was strictly correlated
      with the density of the mononuclear cell infiltrate. The results indicate that
      human lymphoproliferative disease cells possess both local and remote invasive
      ability via the secretion of matrix-degrading enzymes and the induction of
      angiogenesis which is fostered by host inflammatory cells and by an intervening
      ensemble of angiogenic factors.

PMID- 9594365
TI  - The effect of Ginkgo biloba on the activity of catalase and lipid peroxidation in
      experimental strangulation ileus.
AB  - This study was designed to assess the therapeutic effect of Ginkgo biloba extract
      (EGb 761) in experimental strangulation ileus. Rats were divided into control (n
      = 7), placebo (n = 11), and EGb-treated (n = 11) groups. No surgical procedure
      was carried out on the control group. Strangulation ileus was produced in the
      placebo and EGb groups for 2.5 h. At the end of this period, 100 mg/kg EGb in 1
      ml of saline was injected intraperitoneally to the EGb-treated group. In the
      placebo group, animals received an equivalent amount of saline intraperitoneally;
      24 h later, repeat laparotomies were performed to take blood and intestinal
      tissue samples. The EGb treatment decreased tissue malondialdehyde levels and
      increased catalase activities compared with the placebo group (P < 0.05 for
      both). Serum creatine kinase and phosphorus levels were also determined in all
      groups. In the placebo group these were significantly higher than in the control
      group (P < 0.01 and P < 0.05, respectively). In the EGb group these were not
      different from controls and the increase in creatine kinase activity in the EGb
      group was not as high as in the placebo group (P < 0.05). Our results suggest
      that EGb could be preventive against the effects of strangulation ileus in a rat
      model.

PMID- 9594366
TI  - Absence of antibodies to tissue-type plasminogen activator in patients with
      previous deep vein thrombosis.

PMID- 9594367
TI  - A hypercoagulable state in activated protein C resistant patients with ischemic
      stroke.

PMID- 9594368
TI  - [Clinical evaluation of cholesterol embolization syndrome after cardiac
      catheterization].
AB  - The clinical features and outcomes of patients with cholesterol embolization
      syndrome after cardiac catheterization were evaluated. Among 4,920 patients
      undergoing cardiac catheterization during 1991 to 1996, the symptoms, signs,
      laboratory data, treatment and prognosis of eight (6 males and 2 females, mean
      age 69 years old) were reviewed who were pathologically or clinically diagnosed
      as having cholesterol embolization syndrome. All patients had more than two
      coronary risk factors. Mobile plaque of the aortic arch was detected in all five
      patients who underwent transesophageal echocardiography. All patients had one or
      more precipitating factors, including coronary angiography, percutaneous
      transluminal coronary angioplasty, cardiovascular surgery and cardiopulmonary
      resuscitation. The first symptom was renal dysfunction in four patients, skin
      findings of purple toes in two, muscle pain in one and new onset of refractory
      hypertension in one. The time after the precipitating factor to the onset of
      symptoms was 32 +/- 9 days on average. Eosinophilia was found in all patients and
      six patients revealed eosinophilia before the onset of symptoms. Four patients
      showed skin findings of purple toes which progressed in three of the four
      patients even after anticoagulant therapy was discontinued. Epidural anesthesia
      was markedly effective for skin findings of purple toes in two of the three
      patients. Diagnosis of cholesterol embolization syndrome is difficult because
      patients show various symptoms and there is an interval between the precipitating
      factor and the onset of symptoms. However, the conditions of the patients
      deteriorate rapidly and the prognosis is generally poor without supportive
      therapy in the early stage. Our study demonstrated that eosinophilia might be an
      important clue to early detection of cholesterol embolization syndrome.
      Furthermore, epidural anesthesia is effective for skin findings of purple toes in
      patients with cholesterol embolization syndrome. In conclusion, cholesterol
      embolization syndrome should be detected in the early stage based on eosinophilia
      or clinical symptoms after cardiac catheterization, and supportive therapy
      started as soon as possible, including discontinuance of anticoagulant therapy,
      hemodialysis for renal dysfunction and epidural anesthesia for skin findings of
      purple toes.

PMID- 9594369
TI  - [Usefulness of thallium-201 myocardial scintigraphy during hyperventilation and
      accelerated exercise test in patients with vasospastic angina and nearly normal
      coronary artery].
AB  - The usefulness of thallium-201 (201Tl) myocardial scintigraphy was studied in 109
      patients with vasospastic angina who had nearly normal coronary arteries (degree
      of stenosis < 50%). Coronary spasm was confirmed by pharmacologic agents in all
      109 patients from January 1991 to June 1996. The appearance rate of visual
      redistribution on 201Tl myocardial scintigraphy was compared between four groups,
      34 patients performing graded bicycle ergometer exercise starting at a work load
      of 50 W with increments of 25 W every 3 min [Ergo (3) group], 14 patients
      performing hyperventilation for 5 min [HV (5) group], 31 patients performing
      bicycle ergometer exercise with increments of 25 W every 1 min after 5 min
      hyperventilation [HV (5) + Ergo (1) group], and 30 patients at rest (Rest group).
      The value of the visual redistribution rate on 201Tl myocardial scintigrams in
      the HV(5) + Ergo (1) group (65%) was higher than that in the patients of other
      groups [Ergo (3) 41%, HV (5) 43%, Rest 33%]. However, there were no significant
      differences between the four groups. Stress 201Tl imaging after hyperventilation
      and accelerated exercise is useful to disclose ischemic evidence in about two
      thirds of patients with vasospastic angina and nearly normal coronary arteries,
      whereas about 40% of patients had visual redistribution on 201Tl myocardial
      scintigrams by performing standard procedures.

PMID- 9594370
TI  - [Precipitating factors in patients with repetitive exacerbation of chronic left
      heart failure].
AB  - The precipitating factors of repetitive exacerbation were investigated in 110
      consecutive patients with chronic left heart failure admitted due to acute
      exacerbation more than twice to the medical emergency ward of National
      Cardiovascular Center from January, 1992 to December, 1996. The controls were 189
      consecutive patients with chronic left heart failure admitted to the ward due to
      acute exacerbation only once during the same period. Excessive intake of water or
      sodium, overwork and infection were common precipitating factors in the first
      decompensation of left heart failure, but the former two factors became less
      common with repeated admission. Patient mistakes such as excessive intake of
      water or sodium, overwork and noncompliance with medications, and new onset
      arrhythmias were common precipitating factors in patients (n = 13) admitted to
      the ward more than four times. Infection was a common precipitating factor (63%)
      in patients with a time interval between readmission and the last discharge of
      longer than 2 years. Despite repeated admission, infection was a common
      precipitating factor in patients with valvular heart disease (n = 31), patient
      mistakes were common in heart disease with left ventricular hypertrophy (n = 20),
      and infection and new onset arrhythmias were common in dilated cardiomyopathy (n
      = 28) and old myocardial infarction (n = 31). Patient mistakes and new onset
      arrhythmias were the common factors that led to repetitive exacerbation of left
      heart failure, and precipitating factors were characterized by the etiology of
      left heart failure.

PMID- 9594371
TI  - [Automated cardiac output measurement by color Doppler echocardiography].
AB  - Recently, automated cardiac flow measurement (ACM) has been developed for
      measuring the volume flow rate of blood flow through the left ventricular outflow
      tract. Measurements of left ventricular cardiac output by the ACM method were
      compared with those by the thermal dilution method with a Swan-Ganz catheter in
      27 patients (16 men and 11 women; aged 44 +/- 3 years) in whom clear two
      dimensional and color Doppler images of the left ventricular outflow tract were
      obtained. The total time required for left ventricular stroke volume calculation
      by both ACM and pulsed Doppler methods was measured in 10 patients (six men and
      four women; aged 41 +/- 2 years). There was an excellent correlation in the
      measurements of cardiac output between the ACM and thermal dilution methods (y =
      0.77x + 0.77, r = 0.84, SEE = 0.4 l/min). The total time required for left
      ventricular stroke volume calculation by the ACM method was significantly shorter
      than that by the pulsed Doppler method (92 +/- 10 vs 177 +/- 30 sec, p < 0.01).
      The ACM method is simple, quick, and accurate for the automated assessment of
      cardiac output.

PMID- 9594372
TI  - [Atrial fibrillation and thromboembolism: a multicenter cooperative study.
      Research Group for Antiarrhythmic Drug Therapy].
AB  - A multicenter, retrospective study was undertaken to determine the prevalence of
      and risk factors for thromboembolism and efficacy of therapy in patients with
      atrial fibrillation. The primary prevention group consisted of 1,819 Japanese
      patients (mean age 64 years). During the mean follow-up period of 4.6 years. 158
      patients developed cerebral thromboembolism or peripheral embolism (1.9%/year).
      The annual rate of thromboembolic complications was 0.9% for patients without
      underlying heart disease which was significantly lower compared with that for
      patients with underlying heart disease (p < 0.001). The annual rate was 1.4%
      among patients treated with aspirin (alone and in combination with other drugs
      except for warfarin), 1.4% with warfarin (alone and in combination with other
      drugs) and 1.1% with ticlopidine. The risk was lower for patients receiving these
      drugs (2.2%/year, p < 0.001). Among 801 patients not receiving treatment for
      thromboembolism, the annual rate was 0.9% for patients without underlying heart
      disease, which was significantly lower compared with patients with underlying
      heart diseases (e.g., 2.5% for ischemic heart disease and 2.1% for mitral valve
      disease, p < 0.001). Multivariate analysis using quantification method II
      revealed hypertension, sick sinus syndrome and left ventricular dysfunction (> or
      = NYHA class II) as risk factors for embolism. Although limited due to its
      retrospective nature, the present study suggests that the risk for embolism seems
      low in patients with atrial fibrillation but is not associated with underlying
      heart diseases or other risk factors, and antiplatelet treatment seems beneficial
      for these patients.

PMID- 9594373
TI  - Long-term effect of low-density lipoprotein apheresis in a patient with
      heterozygous familial hypercholesterolemia: follow-up study using coronary
      angiography.
AB  - A 62-year-old man with old myocardial infarction and familial
      hypercholesterolemia was treated by both probucol and low-density lipoprotein
      (LDL) apheresis. Coronary angiography was performed before and after 3.5 years of
      LDL apheresis treatment, and no new lesion or progression of coronary
      atherosclerosis was observed. LDL apheresis drastically reduced the serum total
      cholesterol. However, it is still unclear whether LDL apheresis effectively
      prevented the recurrence of cardiac events and the progression of coronary
      atherosclerosis in this patient.

PMID- 9594374
TI  - [Giant mobile mass of the left ventricle in a patient with dilated
      cardiomyopathy].

PMID- 9594375
TI  - Expression of the endogenous galactoside-binding lectin of Xenopus laevis during
      cranial neural crest development: lectin localization is similar to that of
      members of the N-CAM and cadherin families of cell adhesion molecules.
AB  - Cranial neural crest of Xenopus laevis at different stages of development from
      neurulation to metamorphosis was studied for the expression of the endogenous
      galactoside-binding lectin of Xenopus using immunocytochemistry. The presence and
      localization of members of the N-CAM and cadherin cell adhesion families were
      also investigated. Lectin and the other known cell adhesion molecules are
      expressed throughout development and their localization patterns change
      coordinately depending on the development stage. All the molecules colocalize.
      The results suggest that all of these molecules, including the lectin, may be
      involved in cranial development, possibly in cellular adhesion.

PMID- 9594376
TI  - Dental manifestations of osteogenesis imperfecta and abnormalities of collagen I
      metabolism.
AB  - The in vitro protein-chemical features and the molecular background of
      osteogenesis imperfecta (OI), a heritable disorder of collagen I metabolism, have
      been elucidated in recent years. The aim of our study was to find the prevalence
      of dentinogenesis imperfecta (DI) and other dental anomalies in 88 patients with
      OI, to compare clinical with radiologic abnormalities, and to correlate these
      clinical/radiologic findings with the results of gel electrophoresis and
      molecular studies of collagen I. Twenty-eight percent of OI patients had DI. Most
      patients with DI had radiologic abnormalities, but some patients had radiologic
      signs compatible with DI, but no clinical signs of DI. OI type I patients with DI
      were more severely affected by OI than those without DI. In OI type III and IV,
      in contrast, there was no difference in overall severity between patients with
      and without DI. DI was not associated with any particular molecular aberration in
      any OI type. If defining DI from the presence of both clinical and radiologic
      signs, collagen I produced by cultured fibroblasts was qualitatively abnormal
      from all OI patients with DI. Some OI patients had dental abnormalities not
      resembling DI. A qualitative collagen abnormality could not be found in any of
      these patients. Denticles, i.e., calcifications within the pulpal cavity, were
      found more frequently in OI patients than in control subjects.

PMID- 9594377
TI  - Correlation between speech outcome and cephalometric dimensions in patients with
      diastrophic dysplasia.
AB  - Diastrophic dysplasia (DTD) is a recessively inherited form of
      osteochondrodysplasia, presenting with disproportionate short stature and
      multiple orthopedic problems. The clinical oral manifestations include either
      cleft palate or submucous cleft palate in at least half of the patients.
      Histological studies have shown alterations in growth plate, articular,
      laryngeal, tracheal, and ear cartilages. Mutations in the DTDST gene, which codes
      for the sulphate transporter membrane protein, are responsible for the disease.
      Thirty-three patients were studied for speech characteristics and their
      correlation with cephalometric dimensions. Hyponasality was observed in 13 and
      misarticulation of /R/, /S/, or /L/ sounds in 17 of the 33 patients. Neither of
      these correlated with the occurrence of palatal deformities. Hyponasality was
      atypical and did not correlate with the obtained nasalance scores. Cephalometric
      measurements reflecting the size of the orofacial area of the vocal tract were
      short in the DTD patients compared with those in the healthy controls. The
      specific speech characteristics in DTD probably result from both the altered size
      and shape of the vocal tract and the structural and functional abnormalities of
      the laryngeal and tracheal cartilages.

PMID- 9594378
TI  - Ultrastructural and histochemical changes and apoptosis of inner enamel
      epithelium in rat enamel-free area.
AB  - The formation of an enamel-free area (EFA), a region of the dentin without an
      enamel cap at the cusp tip of rodent molar, is thought to depend on the specific
      differentiation and function of inner enamel epithelium of EFAs (EFA cells). The
      authors attempted to clarify both the ultrastructure and alkaline phosphatase
      (ALPase) activity of EFA cells up until tooth eruption by using rat mandibular
      first molars. Apoptosis was also examined. The EFA cells differentiated into
      secretory cells resembling differentiating ameloblasts but without Tomes'
      processes (postnatal day 1-3). No reactivity for ALPase was observed in the EFA
      cells. Enamel-like crystals were detected in close vicinity to dentin crystals at
      this stage. Thereafter, EFA cells became maturative ameloblast-like with ruffled
      border-like structures (postnatal day 5-8) and exhibited a strong reactivity for
      ALPase. These findings suggest that EFA cells change from secretory to absorptive
      cells within a short period and become reduced enamel epithelium at the early
      stage of tooth development. Apoptosis occurs in EFA cells, as it does in
      ameloblasts, but its significance seems to differ between the two cell types.

PMID- 9594379
TI  - Two gene products for beta-galactosidase are differentially expressed in the
      mouse salivary glands.
AB  - The specific activity of GM1 ganglioside beta-galactosidase, also known as
      lysosomal or acidic beta-galactosidase, and the neutral beta-galactosidase were
      determined in the mouse three major salivary glands and compared to other
      tissues. Our data indicate that at pH 4.4, lysosomal beta-galactosidase activity
      in the submandibular gland and the sublingual gland of the mature male is the
      higher than in the parotid gland, kidney, and skeletal muscle. At pH 7.3, neutral
      beta-galactosidase activity is overall much lower and is higher in the
      submandibular gland compared to the sublingual and the parotid glands, kidney,
      and muscle. En bloc histochemical staining of tissues using x-gal as a substrate
      at pH 4.4 demonstrates high beta-galactosidase activity in all three salivary
      glands in comparison to skeletal muscle. At pH 7.3, the submandibular gland
      demonstrates higher activity, whereas the parotid appears negative and the
      sublingual gland demonstrates intermediate activity levels. En bloc staining
      using x-fucose (another substrate of lysosomal beta-galactosidase) demonstrates
      high activity in all three glands at pH 4.4, and no activity in any of the glands
      at pH 7.3. Microscopic histochemistry indicates that beta-galactosidase activity
      is localized to parenchymal cells. Thus, the two gene products for beta
      galactosidase are differentially expressed in the salivary glands. These novel
      findings question the previous use of the bacterial beta-galactosidase (lacZ) as
      a reporter gene in the salivary glands. Endogenous beta-galactosidase activity in
      the salivary glands is probably related to glycoprotein metabolism, processing
      glycoconjugates containing a terminal beta-galactosidic linkage. Further studies
      of beta-galactosidase function and differential regulation in these tissues are
      needed.

PMID- 9594380
TI  - Effect of psychrotrophic microorganisms on the plasmin system in milk.
AB  - The psychrotrophic bacteria that are present in raw milk produce heat-stable
      proteases that affect the plasmin system and, in turn, the quality of the
      processed milk and other dairy products. Three bacterial strains, Pseudomonas
      spp. SRM21A and SRM28A and Pseudomonas fluorescens M3/6, were inoculated at a
      level of approximately 10(3) cfu/ml into reconstituted nonfat dry milk and
      incubated at 4 degrees C for up to 9 d. From each sample, casein and whey
      fractions were obtained and electrophoresed to visualize protein hydrolysis and
      plasmin activity. Colorimetric assays were used to quantify plasmin-related
      activities. The casein SDS-PAGE gels showed that, by 5 d of incubation,
      caseinolytic activity was visible in whey fractions of all three strains at the
      same molecular mass range as commercial bovine plasmin, which was used as a
      control. Colorimetric assays indicated that plasmin activity in the casein
      samples decreased as incubation time increased; plasmin activity in the whey
      samples increased, peaking at 5 to 7 d. Plasminogen activity decreased over time
      in the casein fraction and increased in the whey fraction. Protein
      immunodetection indicated crossreactivity between anti-bovine plasminogen and the
      plasmin and plasminogen from whey samples collected at 5 and 7 d from the
      incubated milk. The growth of the Pseudomonas strains tested and their
      concomitant production of proteases caused the release of plasmin and plasminogen
      from the casein micelle into the whey fraction.

PMID- 9594381
TI  - The digestible amino acid composition of several milk proteins: application of a
      new bioassay.
AB  - The aim of the present study was to determine the composition of amino acids that
      were truly digestible in the ileum. Several bovine milk products and two soy
      protein products were tested using the newly developed enzymatically hydrolyzed
      casein-ultrafiltration (UF) method. This method provides a novel approach for
      determining endogenous flows of amino acids at the terminal ileum, which are
      required for correcting apparent ileal digestibility values to true digestibility
      values. Digestibility was determined by sampling digesta of Sprague-Dawley male
      rats at the end of the small intestine (ileum). Chromic oxide was used as an
      indigestible marker. The traditional protein-free method for determining
      endogenous losses of amino acids was also used for comparison with the
      enzymatically hydrolyzed casein-UF method. Flows of endogenous amino acids at the
      terminal ileum of the rat following peptide alimentation were generally higher
      (1.8-fold) than those determined after a protein-free diet was fed. Compared with
      values for true amino acid digestibility, apparent values underestimated
      digestibility by 2 to 30%. True amino acid digestibility was high (79 to 102%)
      for all of the protein sources. The digestible amounts of methionine and lysine
      were 2 and 1.3 times higher, respectively, in dairy proteins than in soy
      proteins. The enzymatically hydrolyzed casein-UF method provides a physiological
      estimate of endogenous amino acid flow and appeared to be an appropriate method
      for correcting apparent digestibility values to true digestibility values. The
      data for true ileal digestibility of amino acids obtained using this technique
      demonstrated the high quality of bovine milk proteins.

PMID- 9594382
TI  - Oxytocin release and milk removal in ruminants.
AB  - Before milking, less than 20% of the milk yielded by dairy cows is stored within
      the cistern, where it is immediately available for removal. Most of the milk is
      available for the milking machine only after milk ejection, which occurs in
      response to tactile teat stimulation and oxytocin release. For complete milk
      removal, milk ejection is necessary throughout the entire milking process. The
      continuation of stimulatory effect of the milking machine until the end of
      milking is, therefore, essential. Premilking teat stimulation causes induction of
      alveolar milk ejection before the start of milking. Thus, bimodal milk flow
      curves (i.e., interruption of milk flow after removal of the cisternal milk) are
      avoided. Continual ejection of milk is dependent on the presence of elevated
      oxytocin concentrations during the entire milking. Any interruption of the milk
      ejection process can disturb milk removal. Disruption of milk removal can be
      caused by peripheral inhibition of oxytocin effects on the mammary gland or by
      inhibition of oxytocin release by the central nervous system. Peripheral
      inhibition is induced by elevated concentrations of catecholamines through
      stimulation of alpha-adrenergic receptors in the mammary gland, likely via
      changes in ductal resistance. Inhibition of oxytocin release by the central
      nervous system has been observed in primiparous cows immediately after
      parturition, during peak estrus, and during milking in unfamiliar surroundings;
      concentrations of beta-endorphin and cortisol are elevated in this situation.
      However, the role of endogenous opioid peptides in the inhibition of oxytocin
      release in cows remains unclear. In conclusion, during machine-milking, the
      physiological requirements of the cows need to be considered, and, most
      importantly, stressors must be minimized.

PMID- 9594383
TI  - Insulin-like growth factors in plasma and afferent mammary lymph of lactating
      cows deprived of feed or treated with bovine somatotropin.
AB  - The galactopoietic actions of bovine somatotropin are both direct and indirect.
      Indirect actions are apparently mediated by the insulin-like growth factor (IGF)
      system. The objective of this study was to compare systemic (plasma) versus local
      (lymph) concentrations of IGF. Afferent mammary lymph most nearly represents the
      extracellular fluid that is bathing mammary tissue. Catheters were surgically
      implanted in the jugular vein and the superficial afferent mammary lymph vessels
      of four lactating cows. A crossover design was utilized to evaluate the effects
      of bovine somatotropin (bST). After 2 d of basal sampling, either bST (40 mg/d)
      or excipient was administered daily for 5 d. After the conclusion of the bST
      study, a second study was conducted in which cows were deprived of feed for 36 h.
      Blood and lymph were simultaneously sampled at least every 6 h throughout both
      studies. Milk yield was increased by bST, and concentrations of IGF-I were
      increased in plasma and lymph. The relationship between plasma and lymph
      concentrations for IGF-II, bST, insulin, glucose, urea nitrogen, and
      nonesterified fatty acids were similar during bST treatment. Milk yield was
      reduced 76% by 36 h of feed deprivation. Feed deprivation also caused a reduction
      of IGF-I in plasma, but concentrations of IGF-I in lymph were not altered. In
      contrast, changes in IGF-II, bST, insulin, glucose, urea nitrogen, and
      nonesterified fatty acids that were caused by feed deprivation followed similar
      patterns in plasma and lymph. Clearly, if IGF-I mediates the mammary actions of
      bST, then concentrations of IGF-I in plasma correlate with milk yield responses
      as well as, if not better than, concentrations in lymph.

PMID- 9594384
TI  - Effect of sustained-release somatotropin on performance and grazing behavior of
      ewes housed at different stocking rates.
AB  - This study evaluated the effects of recombinant bovine somatotropin (bST; one
      injection of 320 mg per ewe) on milk production and composition and on the
      grazing behavior of multiparous ewes in the third to fourth lactation. Forty
      Comisana lactating ewes were divided into four groups: 1) untreated, grazing on
      natural pasture (botanical composition: 35% of Graminaceae, 49% of Fabaceae, 6%
      of Cruciferae, 10% of other families) at a low stocking rate (16 m2/d); 2)
      untreated, grazing at a high stocking rate (8 m2/d); 3) treated with bST, grazing
      at a low stocking rate; and 4) treated with bST, grazing at a high stocking rate.
      The diets of the ewes were supplemented with vetch and oat hay (500 g/d) and with
      concentrate (500 g/d). Treatment increased milk production (923.8 vs. 669.5 g/d)
      but had little effect on fat and protein contents. Administration of bST
      significantly increased herbage intake; the effect on intake was more marked at
      the high stocking rate. Under these grazing conditions, the treated ewes reduced
      selective intake behavior and, thus, achieved good feed intake despite the low
      biomass availability.

PMID- 9594385
TI  - Effect of diseases on the culling of Holstein dairy cows in New York State.
AB  - The effect of seven diseases on culling was measured in 7523 Holstein cows in New
      York State. The cows were from 14 herds and had calved between January 1, 1994
      and December 31, 1994; all cows were followed until September 30, 1995. Survival
      analysis was performed using the Cox proportional hazards model to incorporate
      time-dependent covariates for diseases. Different intervals representing stages
      of lactation were considered for effects of the diseases. Five models were fitted
      to test how milk yield and conception status modified the effect of diseases on
      culling. Covariates in the models included parity, calving season, and time
      dependent covariates measuring diseases, milk yield of the current lactation, and
      conception status. Data were stratified by herd. The seven diseases and
      lactational risks under consideration were milk fever (0.9%), retained placenta
      (9.5%), displaced abomasum (5.3%), ketosis (5.0%), metritis (4.2%), ovarian cysts
      (10.6%), and mastitis (14.5%). Older cows were at a much higher risk of being
      culled. Calving season had no effect on culling. Higher milk yield was protective
      against culling. Once a cow had conceived again, her risk of culling dropped
      sharply. In all models, mastitis was an important risk factor throughout
      lactation. Milk fever, retained placenta, displaced abomasum, ketosis, and
      ovarian cysts also significantly affected culling at different stages of
      lactation. Metritis had no effect on culling. The magnitude of the effects of the
      diseases decreased, but remained important, when milk yield and conception status
      were included as covariates. These results indicated that diseases have an
      important impact on the actual decision to cull and the timing of culling.
      Parity, milk yield, and conception status are also important factors in culling
      decisions.

PMID- 9594386
TI  - Distribution of radiocarbon after intramammary, intrauterine, or ocular treatment
      of lactating cows with carbon-14 nitrofurazone.
AB  - Three lactating Holstein cows (634 to 698 kg) were dosed, respectively, with 65.6
      mg (44.5 microCi/mg), 131.2 mg (20.1 microCi/mg), or 8.4 mg (141.3 microCi/mg) of
      [14C]nitrofurazone by intramammary, intrauterine, or topical ocular
      administration. Intramammary and intrauterine treatments were single doses;
      ocular treatment was daily for 4 consecutive d (2.1 mg/d). Cows were slaughtered
      after 72-h withdrawal periods. Excreta and milk were quantitatively collected
      from each cow after dosing. Seventy-two hours after treatment, urine, feces, and
      milk contained 62.9, 17.6, and 2.3%, respectively, of the radiocarbon
      administered intramammarily to the cow. Radioactive residues in milk collected
      from the dosed quarter were 150 ppb (nitrofurazone equivalents) and were 39 ppb
      in milk collected from the undosed quarters at 12 h after dosing. Urine, feces,
      and milk from the cow that received the intrauterine dose contained 12.24, 5.17,
      and 0.13% of the administered dose, respectively, at 72 h after treatment.
      Concentrations of total radioactive residues in milk were 9.3 ppb at 12 h after
      dosing. For the cow that was dosed ocularly, the cumulative excretion of
      radiocarbon in urine, feces, and milk was 17.6, 28.5, and 0.5% of the dose,
      respectively. Milk residues from the cow that was dosed ocularly were never > 1
      ppb of nitrofurazone equivalents. Livers and kidneys contained the greatest
      amounts of residues relative to other edible tissues. Parent nitrofurazone was
      not suitable as a marker compound to determine total residues in milk using HPLC
      analysis. Radioactive residues were available systemically and were excreted in
      milk after intramammary, intrauterine, or ocular application of
      [14C]nitrofurazone. Illegal residues in milk and edible tissues would result from
      the administration of nitrofurazone to lactating cows.

PMID- 9594387
TI  - Risk factors for twinning in dairy cows.
AB  - Records for 52,362 lactations over a 10-yr period from 260 dairy farms in North
      America that used a common commercial software for record keeping were evaluated
      for potential risk factors for twinning. Records were evaluated for the
      associations of reproductive disease, parity, production, drug therapy, and the
      occurrence of subsequent twins. The rate of twinning on these farms steadily
      increased over the observation period from 1.4% in 1983 to 2.4% in 1993. The rate
      of twinning also increased as parity of the cow increased, from 1.0% for cows in
      their first lactation to > 4.1% for cows in their fifth or higher lactation. No
      association between twinning and season of year was detected. A multivariate
      logistical regression analysis found that the rate of twinning increased with
      increases in milk production, incidence of cystic ovarian disease, and the use of
      common pharmaceuticals, including GnRH, PGF2 alpha, and antibiotics. Results of
      the regression model also indicated that the single most important reason for the
      recent increase in the rate of twinning was a concurrent increase in milk
      production.

PMID- 9594388
TI  - Effect of extreme walking conditions for dairy cows on milk yield, chemical
      composition, and somatic cell count.
AB  - Thirty-two cows (16 Montbeliardes and 16 Tarentaises) in midlactation were used
      in an experiment utilizing a 2 x 2 factorial arrangement of treatments.
      Throughout the trial, cows received first-cutting cocksfoot hay for ad libitum
      intake supplemented with a fixed amount of concentrate that was individually
      adapted to the milk yield of each cow. During a 23-d experimental period, one
      group of cows walked 9.6 km/d; the other group of cows remained in the barn. Cows
      that walked daily ate less hay (-1.3 and -2.1 kg/d of dry matter for Tarentaise
      and Montbeliarde cows, respectively) and yielded less milk (-1.7 and -2.5 kg/d
      for Tarentaise and Montbeliarde cows, respectively) than did cows that did not
      walk daily. A residual effect of walking on milk yield was observed during the 10
      d following the experimental period. For both breeds, fat content and, to a
      lesser extent, protein content were higher (+6.4 and +1.0 g/kg, respectively) for
      cows that walked. Somatic cell count was also higher for cows that walked
      (+115,000 cells/ml). This difference was more marked in cows that were initially
      infected by a minor or major pathogen (+185,000 cells/ml) than in uninfected cows
      (+47,000 cells/ml) and on the 1st d of walking when walking was linked to
      increases in pH, bovine serum albumin, and immunoglobulin G1 contents of milk
      (+0.08 unit, +0.16 g/L, and +0.19 g/L, respectively). Throughout the experimental
      period, walking induced a rise in body temperature (+1 degree C) and in plasma
      nonesterified fatty acids (+0.63 mM/L). On the 1st d of walking, plasma glucose,
      lactic acid, and cortisol contents were significantly higher for cows that walked
      (+0.25 g/L, +0.64 g/L, and +28.8 ng/ml, respectively).

PMID- 9594389
TI  - The effects of disease, management, and nutrition on average daily gain of dairy
      heifers from birth to four months.
AB  - The effects of disease, management, and nutrition on the average daily gain of
      dairy heifers were studied from birth to 4 mo of age for 795 Holstein calves from
      21 commercial dairy farms in Pennsylvania during 1991 and 1992. Biweekly visits
      to the farms yielded information on body weight, nutrient intake, environment,
      and management practices for each calf. Average daily gain varied throughout the
      4-mo period because of many factors, including housing location after separation
      from the dam, dry matter intake, season, and farm. Dry matter intake was 4.0
      kg/kg of body weight gain throughout the period from birth to 4 mo of age. Calves
      born in winter tended toward higher average daily gain than did calves born in
      other seasons. Calves born in summer showed a tendency for decreased average
      daily gain. The practices of tying calves with cows and housing groups of calves
      in pens were detrimental to average daily gain, but the use of hutches and the
      practice of tying calves away from cows yielded higher average daily gains. Other
      variables with significant effects included calving location, parity of the dam,
      and delivery score at calving.

PMID- 9594390
TI  - Ash content of detergent fibers in feeds, digesta, and feces and its relevance in
      fiber digestibility calculations.
AB  - The influence of insoluble ash in diet, digesta, and fecal samples was evaluated.
      Ash-free values of neutral detergent fiber (NDF) and acid detergent fiber (ADF)
      for feed, digesta, and fecal samples were compared with uncorrected values of NDF
      and ADF in two digestibility experiments. Six feed samples were selected at
      random along with four duodenal and two fecal samples; the latter two were a part
      of two digestion studies. The silica composition of feed samples was low with the
      exception of oat hay and rice straw. Ash-free values of NDF and ADF for digesta
      and fecal samples were lower than uncorrected values of NDF and ADF, and silica
      accounted for the majority of the differences. The use of ash-free values of NDF
      and ADF in both digestibility experiments with dairy cows resulted in more
      realistic digestibility estimates and reduced the amount of variability
      associated with the calculation of the digestibility of NDF and ADF in the rumen
      and total digestive tract. The source of the insoluble ash was not identified but
      could have come from individual feedstuffs or the consumption of sand. Sample
      contamination by silica and other ash components may influence NDF and ADF
      composition if the fiber residues are not ashed prior to calculation of NDF and
      ADF.

PMID- 9594391
TI  - Effects of Yucca shidigera extract and soluble protein on performance of cows and
      concentrations of urea nitrogen in plasma and milk.
AB  - Twelve multiparous Holstein cows averaging 122 d postpartum were used in a
      replicated Latin square design with 21-d periods. Cows were fed diets containing
      either low or high soluble protein supplemented with 0 or 9 g/d of Yucca
      shidigera extract per cow. Dry matter intake and yields of milk, fat, 3.5% fat
      corrected milk, and total solids were not affected by treatment. High soluble
      protein increased percentages of fat and total solids in milk but decreased
      percentages of crude protein and true protein in milk. Yucca shidigera extract
      did not affect percentages or yields of milk components, ruminal NH3 N, or urea N
      in milk or plasma. High soluble protein tended to increase both ruminal pH and
      concentrations of ruminal NH3 N. Yucca shidigera extract did not affect ruminal
      pH or NH3 N. High soluble protein increased concentrations of urea N in plasma
      and milk when both were measured by enzymatic assay, but differences in milk urea
      N measured by mid infrared reflectance spectroscopy were not significant. Neither
      Yucca shidigera extract nor increased ruminally undegradable protein was
      beneficial in this trial when fed to cows milking 30 to 35 kg/d. Concentrations
      of urea N in milk as measured by mid infrared reflectance spectroscopy were
      higher than those measured by enzymatic assay, but measurements by mid infrared
      reflectance spectroscopy were not as sensitive to treatment differences as were
      measurements by enzymatic assay.

PMID- 9594392
TI  - Influence of maturity of grass silage and flaked corn starch on the production
      and metabolism of volatile fatty acids in dairy cows.
AB  - An experiment employing a Latin square design was used to quantify the effects of
      two stages of maturity of grass silage (early cut and late cut) and three
      concentrations of flaked corn starch (0, 2, and 4 kg) on the molar proportion of
      rumen volatile fatty acids (VFA), the production of rumen VFA, and the net fluxes
      of VFA in the splanchnic tissue of cows. The molar proportions of VFA in rumen
      fluid were similar for cows fed both silages. When the silage diets were
      supplemented with starch, the proportion of propionic acid increased for cows fed
      diets containing early cut grass silage, but no effects were found for cows fed
      diets containing late cut grass silage. Estimated gastrointestinal production of
      acetate, propionate, butyrate, and branched-chain fatty acids plus valerate was
      related to intake of metabolizable energy and organic matter fermented into VFA.
      The portal release of acetate was approximately 14% lower than the estimated
      production of acetate by cows fed diets containing early cut grass silage, but
      cows fed diets containing late cut grass silage showed a variable difference
      between estimated production and portal release (31, 24, and 15%, respectively)
      as starch supplementation increased. The portal release of butyrate plus beta
      hydroxybutyrate and the release of branched-chain fatty acids plus valerate were
      approximately 70 and 25%, respectively, of the estimated gastrointestinal
      production. Propionate production was similar to the portal release of
      propionate. Net flux measurements in splanchnic tissue in combination with
      gastrointestinal digestion and kinetics provide information that increases the
      knowledge of pathways and metabolism and quantifies the availability of
      individual nutrients for milk production in dairy cows.

PMID- 9594393
TI  - Influence of nonenzymatically browned soybeans on ruminal fermentation and
      lactational performance of dairy cows.
AB  - Four ruminally fistulated Holstein cows were assigned to one of four total mixed
      rations (TMR) in a 4 x 4 Latin square with 3-wk periods to investigate the
      effects of added lipid from nonenzymatically browned soybeans or soybean oil on
      ruminal metabolism and milk fatty acids. All rations contained 50% forage and 1)
      4% added lipid from soybean oil, 2) 4 or 6% added lipid from nonenzymatically
      browned soybeans, or 3) no added lipid (control). The TMR that contained
      nonenzymatically browned soybeans increased milk C18:2 by 35% compared with the
      TMR that contained soybean oil. A lactation trial was conducted in which 60
      Holstein cows were assigned to one of five TMR from wk 3 to 18 of lactation. The
      TMR contained 1) 4.5% added lipid from soybean oil, 2) 1.5% added lipid from
      nonenzymatically browned soybeans and 3% from soybean oil, 3) 3% added lipid from
      nonenzymatically browned soybeans and 1.5% from soybean oil, 4) 4.5% added lipid
      from nonenzymatically browned soybeans, and 5) 4.5% added lipid from Ca salts of
      long-chain fatty acids. Dry matter intake was reduced by 11% for cows fed the TMR
      containing soybean oil only compared with that for cows fed the other TMR. Milk
      C18:2 and C18:3 were increased as the inclusion of nonenzymatically browned
      soybeans in the TMR increased. All percentages of the nonenzymatically browned
      soybeans fed to cows resulted in fat-corrected milk yields that were similar to
      those of cows fed the TMR that contained Ca salts of fatty acids.

PMID- 9594394
TI  - Systems to evaluate the protein quality of diets fed to lactating cows.
AB  - Ten multiparous and 5 primiparous cows (62 +/- 33 d in milk) were used in a
      replicated 5 x 5 Latin square design to investigate three dietary protein
      evaluation systems for lactating cows: milk protein score, Cornell Net
      Carbohydrate and Protein System, and an increase in Lys and Met to supply 15 and
      5% of the predicted total essential amino acids (AA) in duodenal digesta,
      respectively. Five isonitrogenous diets were evaluated differently by the three
      systems. The milk protein score indicated that formulations of diets 2, 3, 4, and
      5 were of equal quality and better for milk protein synthesis than was diet 1.
      The Cornell Net Carbohydrate and Protein System indicated that diets 3, 4, and 5
      contained adequate AA, but diets 1 and 2 were deficient in Lys and Met. The
      increase in Lys and Met supply indicated that only diets 3 and 5 provided
      adequate Lys and Met. The dry matter intake, energy-corrected production, and fat
      production were lower, and 3.5% fat-corrected milk production tended to be lower,
      for cows consuming diets 4 and 5 than for cows consuming diets 2 and 3. Cows
      consuming diet 1 had lower percentages of crude protein, true protein, and casein
      N in their milk than did with cows consuming all other diets. Cows fed diets 3
      and 5 had higher percentages of protein in milk than did cows fed other diets.
      Protein production was greater, and casein N tended to be greater, for cows
      consuming diet 3 than for cows consuming diet 2. Although all three systems had
      validity, the system by which Lys and Met were increased most accurately
      predicted milk protein percentages and production.

PMID- 9594395
TI  - The effect of ruminal bypass lysine and methionine on milk yield and composition
      of lactating cows.
AB  - Fifty-six multiparous Holstein cows were assigned at 3 wk prepartum to rations
      based on grass silage with 1) corn distillers grains to provide 86 and 90% of
      estimated required metabolizable Lys and Met, respectively; 2) a blend of blood
      meal, fish meal, and meat and bone meal as amino acid (AA) sources to provide 112
      and 103% of required metabolizable Lys and Met, respectively; 3) ruminally
      protected Lys and Met added as a top-dressing to ration 1 to provide 27 g/d of
      Lys and 8 g/d of Met as available AA at the duodenum postpartum; and 4) ruminally
      protected AA for 8 wk postpartum as a top-dressing to ration 1 to provide 40 g/d
      of Lys and 13 g/d of Met as available AA at the duodenum. Cows fed rations 3 and
      4 were offered 13.5 g/d of duodenally available Lys and 4 g/d of duodenally
      available Met for 3 wk prepartum. The total length of the study was 43 wk. Cows
      fed ration 4 consumed 3 to 4 kg more dry matter than did cows fed the other three
      rations, and milk yield and the percentage of milk protein and fat were
      significantly increased during the first 8 wk of lactation. In early lactation,
      cows fed ration 3 had a greater milk fat percentage but similar dry matter
      intake, protein percentage, and yield of 4% fat-corrected milk compared with cows
      fed ration 2. The concentrations of blood serum glutamic oxaloacetic
      transaminase, serum glutamic pyruvic transaminase, triglyceride, and
      nonesterified fatty acids were lower for cows fed ration 4 during the first 8 wk
      of lactation than they were for cows fed the other three rations. The mammary
      arteriovenous difference of whole blood AA indicated that Met along with His and
      Arg may be the most limiting AA for milk yield.

PMID- 9594396
TI  - Fatty acid flow to the duodenum and in milk from cows fed diets that contained
      fat and nicotinic acid.
AB  - Four cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin
      square design; treatments were arranged in a 2 x 2 factorial. Treatments were 1)
      low fat diet, no nicotinic acid; 2) low fat diet, 12 g/d of nicotinic acid; 3)
      high fat diet, no nicotinic acid; and 4) high fat diet, 12 g/d of nicotinic acid.
      Cows were fed for ad libitum intake diets consisting of 35% alfalfa silage, 15%
      corn silage, and either 50% low fat concentrate or 40% high fat concentrate
      (tallow supplied 6.25% of concentrate) and 10% whole raw soybeans (dry matter
      basis). Intake of gross energy (104 Mcal/d) was not different among treatments.
      Ruminal and postruminal digestibility of energy was not altered by fat or
      nicotinic acid. Fatty acid intake and flow to the duodenum were increased by fat
      but were not affected by nicotinic acid. For all diets, flows to the duodenum of
      C16:0, C18:0, total C18, and total fatty acids increased, and flows of C16:1,
      C18:1, C18:2, and C18:3 decreased, compared with their intakes. Biohydrogenation
      of unsaturated C18 was decreased by fat but was not affected by nicotinic acid.
      Digestibilities of C18:0, C18:1, C18:2, C18:3, and total fatty acids that flowed
      to the duodenum were decreased by fat but were not affected by nicotinic acid.
      The yield of C18:0 in milk was increased, and yields of C6:0 to C16:0 fatty acids
      were decreased, by fat, but yields were not affected by nicotinic acid.

PMID- 9594397
TI  - Effect of selenium supplements on the distribution of selenium among serum
      proteins in cattle.
AB  - The objective of this study was to determine the effects of the amount and
      chemical form of dietary Se on the distribution of Se among serum proteins. Six
      growing calves were assigned in a completely randomized design to receive diets
      containing either adequate (0.41 microgram/g) or excess (0.73 microgram/g)
      dietary Se. Proteins in serum collected from the calves were separated into
      albumin, glutathione peroxidase, and selenoprotein P fractions, and the
      concentration of Se in each was determined. The concentration of Se within serum
      was elevated by dietary Se supplementation. The selenoprotein P fraction within
      serum contained the largest percentage of Se among the serum proteins. In a
      second study, 12 mature cows were assigned to receive one of four experimental
      salt mixes containing 20, 60, or 120 micrograms of Se as sodium selenite/g of
      salt mix; the fourth treatment was 60 micrograms of Se as selenized yeast/g of
      salt mix. Cows given salt with 120 micrograms of Se as selenite or 60 micrograms
      of Se as selenized yeast had the highest concentrations of Se in whole blood;
      however, concentrations of Se in serum did not differ among treatments.
      Concentrations of Se in the protein fractions within serum were not affected by
      treatment. Within serum, the highest concentration of Se was in the selenoprotein
      P fraction (31.6 ng/ml), the smallest concentration was in the glutathione
      peroxidase fraction (4.7 ng/ml), and an intermediate amount of Se was obtained
      from the albumin fraction (8.5 ng/ml). In conclusion, selenized yeast and
      selenite as sources of Se for supplementation of cattle resulted in similar
      patterns of Se distribution among proteins in serum. The greatest concentration
      of Se was found in the selenoprotein P fraction, which may contribute to Se
      transportation or function as an antioxidant.

PMID- 9594398
TI  - The effect of vitamin E supplementation of cow diets containing rapeseed and
      linseed on the prevention of milk fat oxidation.
AB  - Two experiments involving lactating Holstein cows were carried out to quantify
      the effect of a 550-g supplement of lipids from extruded rapeseed and linseed on
      milk fatty acid profiles and the susceptibility of milk fat to oxidation. The
      effect of a daily oral supplement containing 9616 IU of vitamin E (all-rac-alpha
      tocopheryl acetate) on milk alpha-tocopherol and protection against oxidation was
      also evaluated. The intake of oilseeds decreased protein and fat contents in
      milk, and the proportion of all C18 fatty acids increased. The trans isomers were
      2.7 and 10.76% of the milk fatty acids, respectively, for cows fed the control
      diet and the diet containing extruded rapeseed and linseed. The ratio of oleic to
      palmitic acid was doubled, and the resistance to oxidation was reduced by 30 to
      40% in both experiments. The dietary vitamin E supplement increased the alpha
      tocopherol concentration in milk by about 45% and was sufficient to prevent milk
      fat depression and oxidation. The diet containing oilseeds and supplemented with
      an adequate amount of vitamin E allowed cows to yield milk that could be used to
      manufacture butter with high oleic acid content, good spreadability, and
      resistance to oxidation.

PMID- 9594399
TI  - The occurrence and replication of Escherichia coli in cattle feeds.
AB  - Sixty-three of 209 (30.1%) samples of cattle feed that were collected from
      multiple commercial sources and from farms were found to contain Escherichia
      coli. However, none of the feed samples examined were culture-positive for E.
      coli O157. Replication of fecal E. coli, including E. coli O157, was demonstrated
      in a variety of feeds at temperatures that were similar to those found on farms
      in summer months. Fresh mixed rations containing corn silage were sampled from 16
      dairies. Rations from 12 of these dairies were found to contain E. coli, and the
      rations from 5 dairies had concentrations of E. coli that were greater than 1000
      cfu/g. The ability of experimental mixed rations to support the replication of E.
      coli was correlated with the concentration of organic acids in the corn silage
      that was used in the ration. Widespread contamination of cattle feeds with E.
      coli and the ability of E. coli to replicate in feeds suggest that feeds are a
      potentially important factor in the ecology of organisms that can be transmitted
      from feces to mouth, such as E. coli O157.

PMID- 9594400
TI  - Selection for economic efficiency of dairy cattle using information on live
      weight and feed intake: a review.
AB  - The objective of this study was to review some of the latest evidence of genetic
      variation in feed intake and feed utilization and to determine how this variation
      might be used. The most important sources of genetic variation in gross
      efficiency are likely to be the quantities of feed eaten and used for yield or
      maintenance and the extent to which body tissue is mobilized. Accounting for just
      one of these components when selection is for improved feed efficiency might
      result in undesirable genetic changes. For example, in an ad libitum feeding
      system, the heritability of body condition score is reported to be 0.43 for
      heifers; genetic correlations of body condition score with milk production and
      live weight were -0.46 and 0.66, respectively. Also, the genetic correlation
      between milk yield and live weight depends on lactation stage. For example, over
      the first 26 wk of lactation, this correlation was reported to be -0.09, but,
      after genetic adjustment for body condition score, the correlation was 0.29. When
      economic values are being derived, energy norms or genetic correlations can be
      used, and double counting of the feed costs needs to be avoided. An index that
      contained linear type traits, however, gave high accuracy of selection. Hence,
      although there appears to be great potential to improve economic efficiency by
      selecting for feed intake and live weight or by possible indicator traits, there
      is still uncertainty about some of the genetic parameters, especially among
      traits related to health, reproduction, and energy balance.

PMID- 9594401
TI  - Detection of putative loci affecting conformational type traits in an elite
      population of United States Holsteins using microsatellite markers.
AB  - Quantitative trait loci affecting conformational type traits were studied in
      seven large grandsire families of US Holsteins using the granddaughter design and
      16 microsatellite markers on 10 chromosomes. The most significant marker effect
      was marker BM203 (chromosome 27) for dairy form in a single grandsire family. A
      multivariate analysis for dairy form and milk yield was also conducted, and the
      result was highly significant, indicating that a segregating quantitative trait
      locus or loci affecting dairy form and milk yield could exist near BM203 on
      chromosome 27. Marker BM1258 (chromosome 23) had a significant effect on udder
      depth. A multivariate analysis on udder depth and somatic cell score was
      conducted for markers 513 and BM1258, and both markers showed significant effects
      on these two traits, indicating that one or several quantitative trait loci
      affecting udder depth and mastitis might exist on chromosome 23. Marker BM4204
      (chromosome 9) had a significant effect on foot angle and on the composite index
      of traits pertaining to feet and legs, indicating that one or several
      quantitative trait loci affecting traits pertaining to feet and legs might exist
      on chromosome 9. Selection on these markers could increase genetic progress
      within these families.

PMID- 9594402
TI  - Effect of full sibs on additive breeding values under the dominance model for
      stature in United States Holsteins.
AB  - Differences in breeding values between dominance and additive models were
      examined theoretically and with field data. Data included 5.2 million records on
      stature from 3.0 million US Holsteins. The largest full-sib family had 29
      animals, and 7% of all animals had at least one full sib. The dominance model,
      which accounted for dominance covariances, included the following effects:
      management, age, stage of lactation, permanent environment, animal additive, and
      parental dominance (one-quarter of dominance variance) as well as a regression
      coefficient for inbreeding percentage. Two reduced models were also assumed; in
      the first, the parental dominance effect was removed, and, in the second, the
      inbreeding regression coefficient was also removed. The correlations between
      breeding values in the three models were > 0.999, but breeding values of some
      animals from full-sib families changed > 5 standard deviations of parental
      dominance. The largest changes were observed for parents with large numbers of
      full-sib progeny, with limited information from parents, and without individual
      performance records. On average, the differences were up to four times larger for
      cows than for bulls and up to five times larger for dams than for sires. The
      greatest differences in breeding values between the dominance and the additive
      models were observed for dams with full-sib progeny, female full sibs, and low
      reliability bulls with full sibs in the extended family. Animals with large
      amounts of additive information as progeny-tested bulls were influenced little by
      the inclusion of dominance. Animals with a large proportion of information coming
      from animals with dominance relationships, such as cows originating via embryo
      transfer changed the most.

PMID- 9594403
TI  - Break-even cost of cloning in genetic improvement of dairy cattle.
AB  - Twelve different models for alternative progeny-testing schemes based on genetic
      and economic gains were compared. The first 10 alternatives were considered to be
      optimally operating progeny-testing schemes. Alternatives 1 to 5 considered the
      following combinations of technologies: 1) artificial insemination, 2) artificial
      insemination with sexed semen, 3) artificial insemination with embryo transfer,
      4) artificial insemination and embryo transfer with few bulls as sires, and 5)
      artificial insemination, embryo transfer, and sexed semen with few bulls,
      respectively. Alternatives 6 to 12 considered cloning from dams. Alternatives 11
      and 12 considered a regular progeny-testing scheme that had selection gains
      (intensity x accuracy x genetic standard deviation) of 890, 300, 600, and 89 kg,
      respectively, for the four paths. The sums of the generation intervals of the
      four paths were 19 yr for the first 8 alternatives and 19.5, 22, 29, and 29.5 yr
      for alternatives 9 to 12, respectively. Rates of genetic gain in milk yield for
      alternatives 1 to 5 were 257, 281, 316, 327, and 340 kg/yr, respectively. The
      rate of gain for other alternatives increased as number of clones increased. The
      use of three records per clone increased both accuracy and generation interval of
      a path. Cloning was highly beneficial for progeny-testing schemes with lower
      intensity and accuracy of selection. The discounted economic gain (break-even
      cost) per clone was the highest ($84) at current selection levels using sexed
      semen and three records on clones of the dam. The total cost associated with
      cloning has to be below $84 for cloning to be an economically viable option.

PMID- 9594404
TI  - Genetic analysis of clinical lameness in dairy cattle.
AB  - Scores for clinical lameness from two separate studies were combined, and genetic
      parameters were estimated based on linear and threshold models. Cows were from 24
      herds in Minnesota, Wisconsin, and Virginia. To evaluate clinical lameness, cows
      were observed walking and were assigned a score between 0 and 4 (where 0 = no
      observable problems to 4 = inability to walk). Data included 1624 records on 1342
      cows. The models included fixed effects of herd visit, parity, and stage of
      lactation. Random effects were additive genetics, permanent environment to
      account for repeated records, and residual. Estimates of heritability were 0.10
      and 0.22 from the linear and threshold models, respectively. The correlation
      between ETA from linear and threshold models based on all animals was 0.974.
      Deregressed ETA of sires and REML were used to estimate genetic correlations
      between clinical lameness and conformation traits. Among the type traits, foot
      angle, rear legs (rear view), and rump width had strongest associations with
      clinical lameness; absolute values for genetic correlations between these traits
      and clinical lameness were approximately 0.65. Low foot angle, hocking in, and
      wide rumps were associated with increased clinical lameness. Correlations with
      strength and body depth ranged from 0.20 to 0.43, indicating that heavier cows
      were more prone to clinical lameness.

PMID- 9594405
TI  - Development of an udder health index for sire selection based on somatic cell
      score, udder conformation, and milking speed.
AB  - Genetic parameters of subjectively scored milking speed and somatic cell score
      were estimated using REML and a sire model. Approximately 250,000 records were
      used. Heritabilities were 0.15 for milking speed and 0.14 and 0.16 for lactation
      mean somatic cell score (SCS) for first and second lactations, respectively.
      Genetic correlations between milking speed and SCS were 0.41 and 0.25 for first
      and second lactations, respectively, indicating that faster milking was
      associated with increased SCS. Genetic parameters for milking speed, SCS, and
      udder conformation were estimated using REML and an animal model. Records from
      approximately 120,000 cows were used. Genetic correlations were greatest for
      udder depth (-0.26) with SCS and for width of rear udder attachment (-0.24) with
      milking speed. An udder health index for use in sire selection was developed for
      an aggregate genotype that included subclinical mastitis in lactations 1 and > or
      = 2, clinical mastitis in lactations 1 and > or = 2, and milking time. Respective
      economic weights were -$12, -$31, -$15, -$59, and -$11 per genetic standard
      deviation. Traits in the selection index were milking speed, udder conformation,
      and SCS in first and later lactations. Standardized weights for a simple index
      for sires based on estimated breeding value from 50 daughter records were 5.5, 
      1.2, 3.5, -3.9, and -8.7 for udder depth, front teat length, milking speed, and
      SCS for first and later lactations, respectively. The accuracy of the index was
      0.776, an increase of 15% over an index with only SCS.

PMID- 9594406
TI  - Evaluation of systematic breeding programs for lactating dairy cows: a review.
AB  - Observing cows in estrus and inseminating them at the optimum time are necessary
      steps for effective reproductive management of a dairy herd. However, larger herd
      sizes can lead to reproductive inefficiency and decreased profits on dairy farms.
      Synchronization of estrus behavior through pharmacological control has been used
      to improve reproductive efficiency. Methods of synchronizing estrus were
      originally devised to decrease the time spent detecting estrus; however,
      systematic breeding programs are now being used for convenience and efficiency in
      reproductive management. Systematic breeding programs provide an organized
      approach for administering artificial insemination (AI) at first service.
      Moreover, reproductive management is based on a methodical approach for the
      entire herd rather than for the individual cow. Targeted Breeding (Pharmacia
      Upjohn, Kalamazoo, MI) consists of a series of three PGF2 alpha injections at 14
      d intervals. For convenience, injections are usually given one day a week to all
      cows that surpass the specified target date. The PGF2 alpha injections may be
      continued until detection of estrus and AI or fixed-time AI. Ovsynch consists of
      a GnRH injection at a random stage of the estrous cycle, followed by PGF2 alpha 7
      d later, a second GnRH injection 36 to 48 h after PGF2 alpha, and timed AI.
      Research has shown that both Ovsynch and Targeted Breeding can improve
      reproductive performance over that of traditional programs.

PMID- 9594407
TI  - Lipopolysaccharide a virulence factor of Helicobacter pylori: effect of antiulcer
      agents.
AB  - Helicobacter pylori plays a major role in the pathogenesis of gastric disease.
      The gastric epithelial integrity is compromised by the H. pylori cell wall
      lipopolysaccharide untoward effect on the gastric epithelial cell receptors
      interaction with proteins of extracellular matrix, glycoproteins of mucus coat,
      and bioactive peptides. These interactions cause the weakening of the mucus coat
      rendering the underying epithelium vulnerable to noxious luminal contents and
      disrupting the regulatory feedback of somatostatin and gastrin. Moreover, H.
      pylori lipopolysaccharide induces histologic lesions typical of acute gastritis
      and these changes are reflected in the increased epithelial cell apoptosis. These
      findings thus identify cell wall lipopolysaccharide as a virulent factor
      responsible for the H. pylori effect on gastric epithelium. The effect of
      antiulcer agents on the interference of lipopolysaccharide with the laminin
      receptor was found to be most efficiently countered by ebrotidine, sulglycotide
      and sucralfate, whereas sulglycotide is the most potent in the reversal of the
      inhibitory effect of the lipopolysaccharide on mucin receptor binding. In the
      case of somatostatin-receptor binding, sulglycotide followed by sucralfate and
      ebrotidine showed the most potency in of reversing the effect of H. pylori
      lipopolysaccharide. Thus these antiulcer agents have a great promise in the
      treatment gastric diseases associated with H. pylori infection.

PMID- 9594408
TI  - Apnoeic responses to pulmonary and systemic challenge of capsaicin in cats.
AB  - The contribution of sensory laryngeal and pulmonary inputs to expiratory apnoea
      and post-apnoeic breathing induced by capsaicin given to pulmonary circulation
      and to aortic arch was studied in the anaesthetized, spontaneously breathing,
      normoxic cats. Breathing was via tracheostomy. Capsaicin (10 micrograms (kg body
      wt)-1) was injected intravenously and to the aortic arch in the intact animal,
      then after section of the superior laryngeal nerves, and finally after
      midcervical vagotomy. Capsaicin, injected as a bolus, induced expiratory arrest
      of breathing on both ways of injection, larger and vagally dependent (P < 0.05)
      on intravenous route, and apparently disparate in ventilatory sequence from the
      systemic challenge. Tidal volume was affected in the opposite direction on either
      route and the respiratory rate increased significantly more with an intravenous
      administration (P < 0.01). Bilateral section of the cervical vagi virtually
      abolished the effects of capsaicin on the breathing pattern independent of the
      site of challenge.

PMID- 9594409
TI  - Decreased hypotensive responsiveness to nitric oxide donor S-nitroso N-acetyl-DL
      penicillamine (SNAP) in spontaneously hypertensive (SHR) rats.
AB  - The aim of the study was to compare hemodynamic effects of intravenously (i.v.)
      applied nitric oxide (NO) donor S-nitroso N-acetyl-DL-Penicillamine (SNAP) in
      conscious spontaneously hypertensive (SHR) to those observed in normotensive
      Wistar Kyoto (WKY) rats. The study was performed on 7 SHR and 8 WKY instrumented
      with polyethylene catheters inserted to the abdominal aorta and vena cava for
      blood pressure (MAP) and heart rate period (HRp) monitoring, and for i.v.
      administration of SNAP (0.05, 0.1, 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, 20.0, 40.0 and
      75.0 microM/kg of body weight). The following differences were found between SHR
      and WKY rats: 1) the threshold dose of SNAP, eliciting significant decrease of
      MAP was markedly higher in SHR (1.0 microM/kg b.w.) than in WKY (0.2 microM/kg
      b.w.), 2) SHR responded with significantly smaller maximum decreases of MAP to
      administration of 1.0, 2.0, 5.0 and 10.0 microM/kg b.w. of SNAP and with smaller
      heart rate acceleration to administration of 10.0, 40.0 and 75.0 microM/kg b.w.
      of SNAP, 3) in SHR MAP decreased progressively, the greatest decline being
      observed after administration of the highest dose (75 microM/kg b.w.) of SNAP
      while in WKY the log dose/delta MAP response curve reached plateau beginning with
      2 microM/kg b.w. of SNAP, 4) the slopes and intercepts of the regression lines
      describing relationship between MAP and HRp after administration of SNAP were
      significantly different in SHR and WKY rats (P < 0.01). The results indicate that
      SHR are significantly less sensitive to hypotensive effects of NO generated from
      moderate doses of SNAP.

PMID- 9594410
TI  - Thrombolytic activity of beta-adrenolytic drug, sotalol.
AB  - Sotalol is a beta-adrenoreceptor blocking drug, the clinical efficacy of which
      has been linked up to its negative chrono- and inotropic effects and its
      hypotensive action. In addition, beta-adrenolytic drugs are known to inhibit
      platelet aggregation in vitro possibly through lowering of calcium ions level.
      Here, we report that in rats sotalol at a dose of 10-20 mg/kg i.v., apart from
      hypotension, evokes instantaneous thrombolytic effect. This is associated with an
      increase in plasma level of tissue plasminogen activator (t-PA). In vitro,
      sotalol at a concentration of 1-100 microM inhibits thrombogenesis on surface of
      rabbit aorta endothelium superfused with blood. Sotalol also has a weak anti
      aggregatory activity (IC50 approximately 500-1000 microM) in human platelet rich
      plasma (PRP). Since the thrombolytic and fibrinolytic but not hypotensive effects
      of sotalol were inhibited by cyclooxygenase inhibitor, indomethacin, while its
      hypotensive but not thrombolytic potency was dimished by an inhibitor of nitric
      oxide synthase, NG-nitro-L-arginine (L-NNA), we have linked up the sotalol
      induced effects in vivo with the release of prostacyclin and nitric oxide. Our
      data point out to a possibility that prostacyclin and nitric oxide concomitantly
      released from endothelium and/or from other blood cells after administration of
      sotalol, may play different roles: prostacyclin may be responsible for
      fibrinolytic, thrombolytic and antithrombotic properties, while nitric oxide may
      take part in the mechanism of sotalol-induced hypotension.

PMID- 9594411
TI  - Influence of cadmium intoxication on thromboresistance of vascular endothelium in
      rabbits.
AB  - Here, using our original technique for measuring of thrombogenesis on the surface
      of rabbit aorta endothelium superfused with whole blood, we demonstrate that the
      thrombogenic property of endothelium is potentiated in the course of 3 months
      cadmium intoxication. The loss of endothelial thromboresistance is accompanied by
      suppressed generation of endogenous prostacyclin, leukopenia, increased platelet
      aggregability and by the presence of quasi-atherosclerotic, focal proliferative,
      glassy-protein lesions formed in aortic endothelium. We hypothesize that the
      final loss of vessel thromboresistance with all sequence of events that accompany
      cadmium intoxication, may result from the cadmium-induced inhibition of the
      generation of endothelial prostacyclin. However, the exact mechanism by which
      cadmium intoxication may affect the generation of prostacyclin and, then,
      functioning of blood platelets and vascular endothelium requires further
      investigations.

PMID- 9594412
TI  - Mechanism by which indomethacin delays the healing of acetic acid-induced ulcers
      in rats. Role of neutrophil antichemotactic and chemotactic activities.
AB  - We have recently discovered a neutrophil antichemotactic factor in the normal
      gastric mucosa of rats. In this study, we examined whether this antichemotactic
      factor as well as chemotactic factors are involved in the indomethacin-induced
      delayed healing of experimental gastric ulcers. Ulcers were induced in male rats
      by a submucosal injection of 20% acetic acid into the gastric wall. Experimental
      rats received a subcutaneous injection of indomethacin at 2 mg/kg once daily for
      28 days, starting at day 0 of ulceration (defined as 5 days after acetic acid
      injection). In the control group (without indomethacin) antichemotactic activity
      was not detected in the ulcerated tissues on day 0, but gradually increased for
      up to 28 days. This activity did not recover in the indomethacin-treated group by
      day 28. However, a high level of neutrophil chemotactic activity was observed in
      the extract of the ulcerated area in day 0. This activity gradually declined as
      the ulcers healed. In the control group, chemotactic activity was negligible
      after dialysis of the extract. In the indomethacin-treated group, however,
      chemotactic activity was maintained from the 10th day after treatment, even after
      the extract was dialyzed. Similar to chemotactic activity, myeloperoxidase
      activity was also augmented significantly in the indomethacin-treated group
      throughout the experiment. We conclude that the mechanism by which indomethacin
      delays ulcer healing is associated with reduced antichemotactic activity and
      increased chemotactic activity in the ulcerated tissues, resulting in the
      persistence of neutrophil infiltration.

PMID- 9594413
TI  - SU-840, a novel synthetic flavonoid derivative of sophoradin, with potent
      gastroprotective and ulcer healing activity.
AB  - Flavonois derived from sophoradine are known to exhibit gastroprotective and
      ulcer healing properties but the mechanism of these actions are not fully
      explained. In this study we determined the effect of novel flavonoid derivative
      of sophoradin, SU-840, on gastric secretion, acute gastric lesions induced by
      acid-independent (100% ethanol) or acid-dependent ulcerogens (acidified aspirin
      (ASA) and stress) and on the healing of chronic gastric ulcers in rats. The
      number and area of gastric lesions was determined by planimetry, gastric blood
      flow (GBF) was measured using H2-gas clearance technique and the mucosal samples
      were excised for the measurement of PGE2 generation by radioimmunoassay. Exposure
      of rats to 100% ethanol or acidified ASA (100 mg/kg dissolved in 0.2 N HCl) or to
      water immersion and restraint stress (WRS) resulted in hemorrhagic gastric
      lesions accompanied by drastic fall in the GBF as compared to the values recorded
      in vehicle treated gastric mucosa. SU-840 (6.25-100 mg/kg i.g.) reduced dose
      dependently gastric acid and pepsin secretion and gastric lesions induced by
      ethanol, acidified ASA and WRS, the dose inhibiting by 50% of these lesions
      (ID50) being 28, 17 and 95 mg/kg, respectively. This protection required much
      lower doses as compared to original sofalcone or sucralfate and was obtained when
      this sofalcone-like drug was administered via parenteral route. The protective
      effect of SU-840 given i.g. or i.p. was accompanied by a marked rise in the GBF
      and mucosal generation of PGE2. The protective activity of SU-840 showed longer
      duration of the action than that of sofalcone and occurred in the doses that
      failed to affect gastric secretion. Pretreatment with indomethacin to suppress
      endogenous PG reversed completely the protective and hyperemic effects of SU-840
      against ethanol and stress induced damage whereas L-NNA, a potent inhibitor of NO
      synthase, failed to affect protection but completely abolished the hyperemia
      evoked by this agent. NEM, an sulfhydryl alkylator, significantly attenuated the
      protective and hyperemic effects of SU-840 suggesting that endogenous sulfhydryls
      are involved in these effects. Seven day treatment with SU-840 accelerated
      significantly healing rate of chronic gastric ulcers and increased the GBF at the
      ulcer crater and ulcer margin. These effects were reversed by L-NNA and further
      restored by the addition to L-NNA of L-arginine, a substrate for NO-synthase. We
      conclude that SU-840 exhibits gastroprotective and hyperemic activity against
      acid-independent and acid-dependent irritants involving endogenous PG,
      sulfhydryls and hyperemia mediated by NO and 2) enhancement in gastric blood flow
      in the ulcer area mediated by NO appears to be essential for the acceleration of
      the ulcer healing by SU-840.

PMID- 9594414
TI  - Effects of acid-degraded products of leminoprazole on acid secretion, mucus
      secretion and synthesis, and indomethacin-induced damage in cell culture.
AB  - We examined the effects of four acid-degraded products of leminoprazole on [1]
      acid secretion by parietal cells, [2] mucus secretion and synthesis by epithelial
      cells and [3] indomethacin-induced damage to epithelial cells. These gastric
      cells were prepared from rabbit stomachs. Upon stimulation with 10 microM
      histamine, acid secretion by parietal cells was inhibited by leminoprazole,
      sulfide and 2-(isobutylmethylamino)benzylalcohol. Sulfide also inhibited
      dibutyryl cyclicAMP (100 microM)-stimulated secretion. However, the inhibitory
      effects of such compounds were observed only at high concentrations, in
      comparison with the antisecretory concentrations of leminoprazole. On the other
      hand, among acid-degraded products, only sulfide enhanced mucus secretion and
      synthesis by epithelial cells. The stimulatory effects of sulfide were the same
      as those of leminoprazole. Furthermore, the effects of sulfide as well as
      leminoprazole were suppressed by NG-nitro-L-arginine methyl ester (L-NAME), and L
      arginine, not D-arginine, prevented the inhibition by L-NAME. In contrast, all
      degraded products failed to protect epithelial cells against indomethacin-induced
      damage. Overall, these results suggest that only the mucus-elevating effect of
      administered leminoprazole may be partly due to the stimulatory effects of
      sulfide derived from leminoprazole on mucus secretion and synthesis by epithelial
      cells.

PMID- 9594415
TI  - A recombinant fragment of Helicobacter pylori CagA affects proliferation of human
      cells.
AB  - The outcome of H. pylori infectins depends on proliferation of various host
      cells, including lymphocytes, monocytes and epithelial cells. In this study we
      showed that a recombinant fusion protein carrying an immunodominant region of H.
      pylori CagA antigen affected the proliferation of human cells. The rCagA
      inhibited PHA-driven T cell proliferation but enhanced the growth of epithelial
      HeLa cells, especially in the presence of granulocyte macrophage colony
      stimulating factor (GM-CSF). When THP-1 monocytes and Kato-3 epithelial cells
      from metastasis of gastric carcinoma were stimulated with GM-CSF, they were also
      susceptible to the inhibitory effect of rCagA. These results confirmed our
      earlier suggestion on the inhibition of T cell function by H. pylori CagA
      protein. However, antiproliferative activity of CagA antigen appears to be not
      restricted to T lymphocytes but modulatory effect of this protein seems to depend
      on the cell type.

PMID- 9594416
TI  - Hormonal responses to exercise in girls during sexual maturation.
AB  - The dependence of hormonal responses to exercise on sexual maturation was tested
      in three-year longitudinal experiment on 34 girls (11-12 years old at the
      beginning of the study). Sexual maturation of the girls was evaluated using
      Tanner scale. Girls were divided into three groups: maturation stages 1-2, 2-4
      and 4-5. Children performed a 20-min cycle exercise at 60% of maximal oxygen
      uptake (VO max) once a year. Cortisol, insulin, somatotropin, beta-estradiol,
      progesterone and testosterone were determined in venous blood by RIA procedures.
      High basal levels of beta-estradiol and somatotropin appeared in stages 2-4 (387
      +/- 92 pmol.l-1) and 12.9 +/- 2.85 ng.ml-1, respectively) and 4-5 (358 +/- 54
      pmol.l-1) and 14.3 +/- 1.53 ng.ml-1, respectively). The basal progesterone level
      increased with maturation, testosterone appeared in the blood in stages 2-4 and 4
      5. The exercise resulted in increased levels of cortisol and somatotropin, and a
      drop in insulin in all girls. The cortisol response was most pronounced in stage
      1-2. Postexercise insulin concentration was the highest in stage 4-5. beta
      estradiol level increased by 23% in stages 1-2 and 4-5, while the response was
      insignificant in stages 2-4. Exercise-induced progesterone increase was
      significant in stage 4-5. In conclusion, sexual maturation associates with
      several quantitative changes in exercise-induced hormonal responses.

PMID- 9594417
TI  - Thyrotropin-releasing hormone affects the oxytocin, vasopressin and prolactin
      release in female rats during midlactation: relation to suckling.
AB  - The effect of thyrotropin-releasing hormone (TRH; 200 ng i.c.v.) on oxytocin
      (OT), vasopressin (AVP) and prolactin (PRL) release was estimated in female
      Wistar rats during midlactation. The hypothalamo-neurohypophysial
      radioimmunoassayed OT and AVP storage as well as blood plasma level of both
      neurohypophysial hormones and PRL in females suckled or not suckled have been
      studied. I.c.v. administration of TRH increased AVP content both in the
      hypothalamus and neurohypophysis of suckled females; however, plasma AVP level
      did not change. TRH increased the hypothalamic as well as neurohypophysial OT
      content during suckling. Simultaneously, TRH inhibited OT release into the blood
      plasma. On the contrary, in not suckled females TRH increased OT plasma
      concentration. I.c.v. TRH raised the PRL concentration in plasma of lactating
      but, at the moment, not suckled females. On the contrary, i.c.v. TRH injection
      into females just suckled was followed by a decrease in PRL plasma level. TRH
      probably acts in the central nervous system as an inhibitory neuromodulating
      factor for the vasopressin release. Also, it cannot be excluded that TRH-
      otherwise known to enhance the PRL release--suppresses the oxytocin-prolactin
      positive feedback mechanism when activated temporarily by suckling.

PMID- 9594418
TI  - Melatonin affects the oxytocin and prolactin responses to stress in male rats.
AB  - Since the pineal-neurohypophysial interactions are now well established and
      oxytocin secretion is known to be a component of the neuroendocrine response to
      the majority of stressful stimuli, the present experiments were undertaken to
      estimate whether melatonin modifies the response of oxytocinergic neurons to the
      immobilization stress. Oxytocin (OT) content in the hypothalamus and
      neurohypophysis as well as plasma level of OT, prolactin (PRL) and
      adrenocorticotropin (ACTH) were studied after melatonin treatment in sham
      operated or pinealectomized male rats. In sham-operated rats, melatonin
      diminished the hypothalamic OT content as well as plasma OT and PRL
      concentrations, but was without effect on neurohypophysial OT and plasma ACTH
      levels in otherwise not treated rats. In both wehicle- or melatonin-treated rats,
      food and water deprivation did not affect the OT, PRL and ACTH secretion. Under
      stress conditions, however, pituitary OT storage was diminished in vehicle
      treated rats and melatonin augmented this response of OT to stress. Melatonin
      also diminished the PRL and ACTH secretion into the blood in stressed rats. In
      pinealectomized animals neither hypothalamo-neurohypophysial OT content nor
      plasma OT, PRL or ACTH concentrations were modified by melatonin treatment in
      animals otherwise not treated or in those deprived of food and water for 24 hrs.
      However, melatonin increased the pituitary oxytocin content as well as plasma OT
      and ACTH concentrations in immobilized animals. Plasma PRL concentration was
      diminished after melatonin treatment in stressed rats. The results suggest that
      the response of oxytocinergic neurons to immobilization stress is augmented by
      melatonin. The effect of melatonin on the OT, PRL and ACTH secretion is modified
      by pinealectomy.

PMID- 9594419
TI  - Effect of indomethacin on nicotine-induced ACTH and corticosterone response.
AB  - The effect of nicotine on ACTH and corticosterone secretion and possible
      mediation of prostaglandins in this secretion was investigated in conscious rats.
      Nicotine (5 and 10 mg/kg i.p.) considerably increased the plasma ACTH and
      corticosterone levels, measured 1h after injection. Mecamylamine (10 and 50
      micrograms i.c.v.), a nicotinic receptor antagonist, given 15 min prior to
      nicotine dose-dependently diminished the ACTH and corticosterone responses, by 59
      and 30% respectively. Pretreatment with hexamethonium (2 mg/kg i.p.), a
      peripheral blocker of nicotinic receptors, diminished to a similar extent the
      nicotine-induced ACTH and corticosterone responses. On the other hand atropine, a
      muscarinic receptor antagonist, did not markedly alter those responses. Systemic
      or intracerebroventricular pretreatment with indomethacin (2 mg/kg i.p. or 0.1
      and 1 microgram i.c.v.), a cyclooxygenase and endogenous prostaglandin synthesis
      blocker considerably reduced, by 58%, the nicotine-induced ACTH response, but did
      not alter the corticosterone response. These results show that nicotine given
      systemically stimulates ACTH and corticosterone secretion by selective activation
      of central and peripheral acetylcholine nicotinic receptors. Endogenous
      prostaglandins are significantly involved in the nicotine-induced central
      stimulation of ACTH secretion. Prostaglandins do not directly affect the nicotine
      induced corticosterone secretion from the adrenal cortex.

PMID- 9594420
TI  - The effects of buspirone on the behaviour of control and stressed mice.
AB  - The effects of buspirone on the locomotor activity and behaviour in the plus-maze
      and hole-board tests were studied in control and small platform stressed mice.
      Small platform stress for 24 hours increased the locomotor activity of mice and
      induced anxiolytic-like effect in the plus-maze and hole-board tests.
      Administration of buspirone either did not affect (2.0 and 4.0 mg/kg) or
      inhibited (8.0 mg/kg) locomotions in control animals. The inhibition of locomotor
      activity by buspirone was greater in small platform stressed mice. In control
      mice buspirone in doses 2.0 and 4.0 mg/kg exerted anxiolytic effect in the plus
      maze and hole board test that was reflected by an increase in the percentage of
      entries onto and the percentage of time spent on the open arms of the plus-maze
      and increased number of head-dippings in the hole-board test. In contrast, in
      small platform stressed mice, buspirone did not induce anxiolytic action in the
      plus-maze and hole-board tests at any dose tested. In doses 2.0 and 4.0 mg/kg
      buspirone produced a sedative effect that was reflected by a decrease in the
      total number of entries made onto the open and into the closed arms of the plus
      maze and a decrease in the number of head-dippings and rearings in the hole-board
      test. These data suggest that small platform stress induces a sensitization of
      mice to the motor depressant effect of buspirone. At the same time small platform
      stress induces hyposensitivity to the anxiolytic effect of buspirone. It is
      proposed that these changes might be due to alterations in the serotonergic
      transmission or to changes in the release of corticosterone.

PMID- 9594421
TI  - Studies on the modulation of DNA damage. 1: A simple kinetic model for
      radioprotection of DNA in aqueous solution.
AB  - A simple kinetic model, based on the assumption that direct and indirect
      interactions of ionising radiations with DNA lead to formation of DNA-radicals
      which are precursors of single strand break (ssb) and double strand break (dsb)
      is presented. Considering accessibility of OH attack on DNA and assuming
      homogenous kinetics, the model has been validated by using experimental data on
      radiation-induced strand break formation in presence of methanol (MeOH) and
      glutathione (GSH). Fitting the D37 values for ssb in aqueous solution of pBR322
      DNA in the presence of the predominantly A-T minor groove-ligand Hoechst 33258,
      the value of the rate constant of OH scavenging by DNA-bound Hoechst was
      estimated by Martin and his group as 2.7 x 10(11) dm3 mol-1 s-1 (Martin, R.F. and
      Denison, L. (1992), Int. J. Radiat. Oncol. Biol. Phys., 23, 578-584). Using
      aqueous solution of calf thymus DNA in the presence of Hoechst this rate constant
      has been determined by pulse radiolysis as 1.1 x 10(9) dm3 mol-1 s-1. The yield
      of strand breaks has also been measured by low angle laser light scattering.
      Using the experimentally measured value of the rate constant of OH scavenging by
      DNA-bound Hoechst in the model, calculations show that OH scavenging alone could
      not explain the overall protection provided by Hoechst; there should be quenching
      of DNA-radicals by Hoechst. Fitting the yield of radiation-induced ssb (G(ssb))
      obtained for CT DNA and pBR322 DNA, the rate constant of this DNA-radical
      quenching has been calculated as 10(6) dm3 mol-1 s-1, which agrees with pulse
      radiolytic data. Using these rate constant values, calculations show that the
      protection against radiation-induced dsb formation provided by the combination of
      Hoechst with GSH is more than that by the combination of MeOH with GSH.

PMID- 9594422
TI  - Chemical modifications and dissociation characteristics of tyrosine and
      tryptophan residues in alpha-crystallin.
AB  - A quantitative estimation of surface accessibility of aromatic residues in alpha
      crystallin from goat lens has been accomplished by chemical modifications using
      different specific reagents having varying sizes. Results of modification of
      tyrosine residues with N-acetylimidazole and tetranitromethane when combined with
      those of ionization studies carried out with hydroxyl ions having the smallest
      size reveal different classes of tyrosine residues in the native protein: 78 +/-
      2 residues have been found to be easily available for modification; among the
      rest, 94 +/- 2 residues appear to be comparatively less exposed to the reagents
      while 28 +/- 2 residues are found to be completely unavailable for modification
      in the native protein and are modified only when the protein is denatured.
      Modification of tryptophan residues with H2O2 also indicates different classes of
      these residues available for oxidation at different concentrations of the
      oxidant. 34 +/- 2 residues of tryptophan are found to be easily oxidized at a
      lower concentration of H2O2 during the first phase of the reaction. The remaining
      tryptophan residues appear to be less exposed to the reagent. This is also
      corroborated from the studies of reactivities of these residues towards another
      specific but bulkier reagent, 2-hydroxy-5-nitrobenzyl bromide. These surface
      exposed aromatic residues in alpha-crystallin may be considered to be vulnerable
      to in vivo oxidative modifications forming insoluble aggregates which may finally
      contribute to the formation of cataract.

PMID- 9594423
TI  - Electric field mapping and structure-activity relationship for cardiotonic
      activities of medorinone and some of its analogs.
AB  - Medorinone 5-methyl-1,6-napthyridin-2(1H)-one and some of its analogs having
      varying degrees of cardiotonic potency have been studied by molecular orbital and
      electric field mapping methods. Ground state geometries of the molecules were
      optimized using the MNDO molecular orbital method. Hybridization displacement
      charges (HDC) combined with Lowdin charges as well as Mulliken charges were used
      for electric field mapping around the molecules. Electric fields near the O2 site
      of medorinone and its analogs correlate well with their observed cardiotonic
      potencies. This result is in agreement with certain pharmacological models for
      cardiotonics.

PMID- 9594424
TI  - NMR and molecular dynamics studies of tachykinins: conformation of the C-terminal
      pentapeptide of substance P(SP7-11).
AB  - Substance P belongs to the tachykinin family of neuropeptides which exhibit
      diverse pharmacological activity. The conformation of Phe1-Phe2-Gly3-Leu4-Met5
      NH2 the C-terminal pentapeptide of substance P (SP7-11) has been studied by NMR
      and molecular dynamics (MD) methods. NMR studies were carried out both in DMSO-d6
      and 95% H2O. Based on the observed chemical shifts, 3JNH alpha coupling
      constants, temperature coefficients of chemical shifts of NH resonances and the
      pattern of inter- and intraresidue NOE's, a predominantly extended backbone
      conformation has been deduced for the peptide in both DMSO and H2O. MD
      calculations carried out in vacuo indicate that the global minimum energy
      conformation of the molecule is folded with an intramolecular hydrogen bond
      between the protonated N-terminal and the C-terminal CONH2 group. The simulation
      shows that beta-turns are energetically unfavourable, while alpha-helices are
      seen to be unstable for the peptide. gamma-Bends at either Gly3 or Leu4 are the
      most preferred ones. Simulations carried out in DMSO as well as in water show a
      preference for a nearly extended conformation.

PMID- 9594426
TI  - Purification and tissue/species dependence of the specificity of buffalo kidney
      cathepsin B.
AB  - A simple purification scheme was developed for isolation and purification of
      cathepsin B from buffalo kidney. The use of CM-Sephadex and chromatofocusing
      helped in better and simultaneous separation of cathepsin B, H and L. As judged
      by PAGE and SDS-PAGE studies, the enzyme was found to be pure on the basis of
      charge and had a molecular mass of 25.5 kDa. The amino acid composition, number
      of free sulfhydryl groups and other major physico-chemical properties of the
      purified enzyme were similar to the properties reported for cathepsin B from
      other sources/tissues. However, the NH2-terminal amino acid residue of the enzyme
      was found to be Ala as against Leu reported from other tissues/species. The total
      carbohydrate content was also found to be significantly lower (3.6%) as compared
      to 7.0-7.6% reported for the enzyme from other sources. Thiol reducing compounds
      activated the enzyme whereas thiol blocking compounds inhibited it. The buffalo
      kidney enzyme hydrolyzed Z-Phe-Arg-MCA (Vmax/K(m) = 17.1) as the most efficient
      substrate followed by Z-Arg-Arg-MCA, BANA and BAPNA. Among the protein
      substrates, goat hemoglobin (Vmax/K(m) = 874) was found to be the most preferred.
      Rabbit muscle aldolase, usually considered to be a good substrate for cathepsin
      B, proved to be a poor substrate for this enzyme; only 25-30% inactivation of
      aldolase was observed. Antibodies raised against the enzyme recognised only
      cathepsin B and did not have any cross reactivity with cathepsin H or L from the
      same or different sources. These differences in the properties of the buffalo
      kidney enzyme vis-a-vis the same enzyme from other tissue/species have been
      attributed to specialized function of cathepsin B in diversified tissues.

PMID- 9594425
TI  - Binding of water and solute to protein-mixture and protein-coated alumina.
AB  - Extent of water vapour adsorption (n1) of gelatin and bovine serum albumin and
      their mixtures in different proportion respectively has been measured by
      isopiestic vapour pressure methods at various values of water activity (a1)
      ranging between zero and unity. Similar measurements have also been carried out
      with gelatin and BSA coated alumina powder. At a given value of a1, n1 for the
      protein mixture is found to be significantly less than their ideal value obtained
      from the additivity rule. Such decrease is probably due to the protein-protein
      interaction as a result of which some of the water binding sites become
      unavailable for water vapour adsorption. On the other hand when a protein is
      mixed with alumina powder, the water vapour adsorption of the protein coated
      alumina surface at a given water activity is found to be 2 to 3 times larger than
      its ideal value obtained from the additivity rule. The standard free energy
      changes for hydration of protein mixtures and protein-coated alumina have been
      evaluated using Bull equation. The extent of excess hydration of these proteins
      and their mixtures as well as protein-coated alumina in the presence of excess
      neutral salts and urea respectively have been evaluated using the isopiestic
      method. In all cases, the moles of water and solute respectively bound in
      absolute amount to biopolymers, biopolymer mixtures and protein-coated alumina
      have been evaluated in the limited range of solute concentrations in the medium.
      Based on the Gibbs-Duhem equations, a rigorous expression for the standard free
      energy change for binding of excess solute and solvent to biopolymer have been
      evaluated with reference to unit solute mole fraction as standard state. Free
      energies of excess hydration of different biopolymer systems have been evaluated
      using this equation.

PMID- 9594427
TI  - Oxalate binding protein from the kidney of rat and human mitochondria: studies on
      properties.
AB  - The oxalate binding protein of rat and human kidney mitochondria were extracted
      by Triton X-100 and purified on Sephadex G-200 column followed by HPLC. Their
      molecular masses were found to be 62 kD and 58 kD respectively, rich with
      arginine and acidic amino acids, 7% of carbohydrates and 1% of inorganic ions.
      Antibodies raised to the rat protein inhibited the oxalate binding and cross
      reacted to the human protein as well as rat liver protein. The binding of oxalate
      to the protein was rapid, reversible, dependent on concentration of oxalate,
      temperature sensitive and inhibited by oxalate analogues. The saturation reached
      at 175 nM oxalate for rat protein with a Kd of 33.3 nM and Bmax of 21 nmoles
      while for human protein the saturation reached at 183 nM oxalate and had a Kd of
      41 nM and Bmax of 14 n moles. The half-saturation concentration of inhibitor
      (IC50) of oxalate was 0.25 microM for rat protein and 0.225 microM for human
      protein while the structural analogues of oxalate had higher IC50 values.
      Proteoliposomes showed accumulation of oxalate confirming transport function of
      the protein. The rat protein promoted calcium oxalate crystallization in vitro
      better than that of human protein and antibody inhibited the crystal growth in
      vitro.

PMID- 9594428
TI  - Phosphoinositide signal transduction pathway during regeneration following
      partial hepatectomy.
AB  - Phosphorylation of endogenous phosphatidylinositol was transiently increased
      following partial hepatectomy but was suppressed during peak DNA synthesis.
      Formation of inositol trisphosphate was decreased while generation of
      diacylglycerol and its breakdown to phosphatidic acid was increased. In response
      to partial hepatectomy protein kinase C was activated due to translocation from
      cytosol to particulate fraction, but the membrane bound activity was decreased
      during regeneration. Alteration of certain parameters in the signal transduction
      pathway apparently facilitates cell proliferation.

PMID- 9594430
TI  - Effects of exogenous phytohormones on plastid tRNA modifications in ragi
      coleoptiles.
AB  - The effects of phytohormones on plastid tRNA modifications were investigated in
      ragi (Eleucine coracana) coleoptiles. Intact 7-day old dark-grown ragi seedlings
      were given phytohormone, indoleacetic acid (IAA) or isopentenyladenine (i6A)
      treatment and grown in the dark or under white fluorescent light; coleoptiles
      were harvested 24 hr following treatment, and plastid total tRNAs were isolated
      and analyzed for their content of modified nucleotides. A total of 14 modified
      nucleotides were identified in the total digests of ragi plastid total tRNA
      preparations; significant increases in the content of some modified nucleotides
      were observed following treatment of phytohormones in the dark and light. The
      relative amounts of pT, pm1G, pm7G and pm1A in IAA-treated dark-grown, pi6A, pm2G
      and pCm in IAA-treated light-grown, and pT and pm2G in i6A-treated light-grown
      ragi coleoptiles were 2 to 10 times higher than the untreated control coleoptile
      plastid total tRNA. In order to gain a better understanding of the effects of
      phytohormones on ragi plastid tRNA modifications, we purified plastid
      tRNA(Ile)(GAU) from coleoptiles of the aforementioned ragi seedlings and analyzed
      its modifed nucleotide content. We find that the content of pGm was 4 to 5 times
      higher in the tRNA(Ile)(GAU) purified from i6A- or IAA-treated dark-grown
      coleoptiles, and pm7G was 5 to 6 times higher in the tRNA(Ile)(GAU) of i6A
      treated light-grown ragi coleoptiles. These results suggest that the synthesis or
      activity of some plastid-specific tRNA-modifying enzymes may be enhanced by i6A
      and IAA with two different modes of regulation, one operating in the light and
      the other operating in the dark.

PMID- 9594429
TI  - 2-Deoxy-D-glucose induced modulation of DNA damage repair, survival, mutagenesis
      and recombinogenesis in 8-MOP+UVA treated yeast.
AB  - Cellular and genomic effects of post-treatment repair modulation by 2-deoxy-D
      glucose (2-DG) and yeast extract were studied in 8-MOP + UVA treated cells of
      Saccharomyces cerevisiae. The type of lesions and their repair in phosphate
      buffer glucose (PBG) differed with UVA dose. At low UVA dose (1.4 kJ/m2), lesions
      were sublethal and mutagenic and did not repair by recombinogensis. The fraction
      of potentially lethal lesions and lesions repaired by recombinogenesis increased
      with UVA dose. Cellular repair in PBG was largely error-free and was inhibited by
      2-DG. Yeast extract enhanced cellular repair and also recombinogensis; 2-DG in
      presence of yeast extract promoted error-prone repair. Pulsed-field gel
      electrophoresed chromosomal DNA bands did not show observable alterations
      immediately after 8-MOP + UVA treatment. On post-treatment incubation in PBG, the
      intensity ratio (rho n), of each band altered in a biphasic manner showing
      decrease first, followed by either increase or no change upto 24 hr depending
      upon UVA exposure dose. Presence of 2-DG in PBG inhibited decrease in rho n in a
      concentration dependent manner. Yeast extract reduced the time of first phase of
      DNA repair. 2-DG and yeast extract together reduced the time of first phase of
      repair and also inhibited the subsequent increase in rho n, which was observed in
      the case of yeast extract in PBG. It is proposed that (i) 2-DG in PBG inhibits
      excision of DNA damage and error-free repair; (ii) yeast extract stimulates the
      error-prone repair associated with cell cycle and recombinogenesis; (iii) 2-DG in
      presence of yeast extract allows excision of damage but inhibits build up through
      recombinogenesis inducing instead, cell cycle associated error-prone repair. A
      simple schematic model has been proposed to explain these events.

PMID- 9594431
TI  - 500 picosecond molecular dynamics simulation of amphiphilic polypeptide Ac(LKKL)4
      NHEt with 1,2 di-mysristoyl-sn-glycero-3-phosphorylcholine (DMPC) molecules.
AB  - Molecular dynamics (MD) simulation of the interaction between amphiphilic
      polypeptide Ac(LKKL)4NHEt and 4 DMPC (1,2 di-mysristoyl-sn-glycero-3
      phosphorylcholine) molecules has been carried out at 310 K for 500 picoseconds
      (ps) using AMBER 4.0. Interaction energy and a number of conformational
      parameters are calculated for the subaveraged coordinates, using P-CURVES 3.1 and
      our MD trajectory analysis program ANALMD. No significant change in DMPC
      headgroup conformation was observed. However, the mobility of P atoms was found
      to be restricted. The chains were quite flexible and their flexibility increased
      towards the ends. They interacted amongst themselves. The polypeptide remained
      predominantly in alpha-helical conformation. Leu1 and Lys2 at the N terminus and
      Leu13 to Leu16 at C terminus assumed non helical conformation and were quite
      flexible. Average interaction energy between the polypeptide and DMPC molecules
      was found to be -151.828 kcal*mol-1. The main contributory factor was
      electrostatic interaction of Lys NH3+ groups with the DMPC phosphates. On an
      average one Lys chain interacted with 1.5 DMPC molecules. Central region of the
      polypeptide had better contact with DMPC molecules. A model for the fusogenic
      properties of the polypeptide is presented on the basis of MD results.

PMID- 9594432
TI  - Oxidative stress and metabolic control in non-insulin dependent diabetes
      mellitus.
AB  - The aim of this study was to evaluate conjugated dienes in subjects with non
      insulin-dependent diabetes mellitus (NIDDM) and its metabolic control. To achieve
      good metabolic control in addition to dietary management oral hypoglycemic agents
      such as glibenclamide, gliclazide and metformin were given to patients. Human
      plasma low-density lipoproteins (LDL) were delipidised and triglycerides (LDL-TG)
      and cholesterol esters (LDL-CE) were separated. Conjugated dienes in LDL-TG and
      LDL-CE of subjects with NIDDM (n = 90) and normal glucose tolerance (NGT) (n =
      30) were measured using second derivative of uv absorption spectrum. Hypoglycemic
      agents lowered substantially concentration of cis, trans (c, t) and trans, trans
      (t, t) conjugated dienes in LDL-CE and LDL-TG. The duration of NIDDM has shown
      significant correlation (p < 0.001) with conjugated dienes in LDL-TG.
      Concentration of c, t and t, t-conjugated dienes in LDL-CE and LDL-TG were found
      significantly higher in subjects with NIDDM than NGT (p < 0.001). In conclusion,
      NIDDM, status of metabolic control and duration of diabetes have strong positive
      relation with oxidative stress.

PMID- 9594433
TI  - Free lysine, glycine, alanine, glutamic acid and aspartic acid reduce the
      glycation of human lens proteins by galactose.
AB  - The amino acids lysine, glycine, alanine, glutamate and aspartate formed adducts
      with galactose at physiological pH and temperature as shown by incorporation of
      U[14C] galactose. The percentage of galactose reacting with lysine, glycine,
      alanine, glutamate and aspartate was 4.5 to 7.8, 7.9 to 10.8, 3.2 to 4.6, 2.8 to
      4.8 and 3 to 5.2, respectively. Studies with lysine showed that the extent of
      glycation of the free amino acid increased with time. Incubation of lens
      homogenate with galactose, effected glycation of proteins. Addition of lysine in
      concentrations of 5 and 10 mM to equimolar concentrations of galactose decreased
      the glycation of lens proteins by 64% to 71%; glycine, alanine, glutamate and
      aspartate decreased glycation by 23 to 68%, 32 to 61%, 35 to 56% and 26 to 61%
      respectively. Under similar conditions, glycine reacts to a greater extent than
      lysine, alanine, glutamic and aspartic acids. However, lysine was more effective
      than glycine, alanine, aspartic and glutamic acids in decreasing glycation of
      lens proteins by galactose. The decrease of glycation with added lysine increased
      with time. In general increase of amino acid concentration rather than that of
      sugar augmented the decrease of glycation of lens proteins.

PMID- 9594434
TI  - Inhibition of angiotensin converting enzyme from sheep tissues by captopril,
      lisinopril and enalapril.
AB  - Inhibition of angiotensin converting enzyme(EC 3.4,15.1, ACE) in presence of
      captopril, lisinopril and enalapril were investigated in kidney, lung and serum
      of sheep using Hip-His-Leu(HHL) as substrate. The activity in kidney, lung and
      serum was inhibited at HHL concentration above 5 mM. The inhibitory constants
      (IC50) ranged between 5.6 nM for serum ACE with lisinopril and 70000 nM for renal
      ACE with enalapril while Ki ranged from 1.0 nM for serum ACE with lisinopril to
      12000 nM for kidney ACE with enalapril. Differences in inhibition observed in
      different tissues suggest that the inhibitors may block function(s) of ACE to
      varying degrees in each tissue.

PMID- 9594435
TI  - Purification and characterization of neutral invertase from chickpea nodules.
AB  - Neutral invertase from nodules of chickpea (Cicer arietinum L.) was isolated and
      purified by ammonium sulphate fractionation, gel filtration and DEAE-cellulose
      column chromatography. The purified enzyme was stable between 0 to 40 degrees C
      beyond which it was irreversibly denatured. Optimum temperature and pH of the
      enzyme were 37 degrees C and 7.0, respectively. K(m) for sucrose was 14.2 mM and
      Vmax was 4.8 mumole hr-1. The enzyme was inhibited by several metal ions. From
      the temperature effect on K(m) and Vmax values, the energy of activation (Ea),
      enthalpy change (delta H) and entropy change (delta S) of the enzyme were
      calculated to be 147 kJmol-1, -4.10 kJmol-1 and -2.33 JK-1mol-1, respectively. By
      employing photo-oxidation and chemical modification and by studying the effect of
      pH on K(m) and Vmax, the involvement of sulphydryl-, imidazole- and alpha-amino
      groups in the active site of the enzyme has been indicated.

PMID- 9594436
TI  - A microtiter plate assay for superoxide using MTT reduction method.
AB  - A simple, rapid and sensitive microtiter plate assay for superoxide using the
      reduction of tetrazolium dye MTT to its coloured formazan has been developed. The
      colour formed can be measured using a microtiter plate reader and the extent of
      reduction of MTT indicates the amount of superoxide generation. A comparison of
      the sensitivities of different procedures for the quantitation of superoxide
      generated by X-XO system has been made. The MTT reduction due to superoxide was
      confirmed by inhibiting the reduction using purified superoxide dismutase. Using
      this method superoxide generation by mitochondria and microsomes was demonstrated
      and this procedure is suitable for detection of intracellularly generated
      superoxide. The proposed method is inexpensive and is suitable for a routine
      analysis of large number of samples.

PMID- 9594437
TI  - Methacrylonitrile induced oxidative stress in rat liver.
AB  - MeAN administration (40mg/kg body wt/day (i.e. 1/5 of LD50) resulted in increased
      levels of lipid peroxidation products, conjugated dienes and lipofuscin-like
      substances in rat liver. Significant decrease in GSH and a decreased activity of
      hepatic SOD, CAT and GPx were observed. There was also an increase in glutathione
      S-transferase and G6PD activities, decreased plasma ceruloplasmin and vitamin C
      implying oxidative stress caused by MeAN.

PMID- 9594438
TI  - Scientific journals in the era of computerization: easy drafting but declining
      quality of illustration.

PMID- 9594439
TI  - Genetic instability and cancer.
AB  - It is well known that defects in some aspects of DNA metabolism including
      telomere maintenance, nucleotide excision repair and mismatch repair contribute
      to tumor development. However, to account for the multiple mutations observed in
      cancer cells, the new fields of DNA metabolism that maintain genome integrity
      must be determined. I will show four new aspects of genetic instability that have
      recently emerged which helps toward the understanding of the links between
      defects in genome integrity and tumor development. First, mutations in DNA
      helicase genes cause rare genetic instability syndromes, suggesting that defects
      in DNA helicase activities are responsible for predispositions to cancers.
      Second, mutations of the gene for ataxia-telangiectasia in sporadic leukemias
      suggest that genes involved in rare syndromes are paradigms for understanding the
      mechanism underlying the genesis of sporadic tumors. Third, since the emergence
      of a link between breast cancer susceptibility gene products and RAD51, great
      interest has been shown in recombinational repair. Finally, a mutator phenotype
      is conditional in some mismatch-repair deficient cells, proposing that cancer
      arises under restrictive conditions even though stability genes are mutated.

PMID- 9594440
TI  - CD34+ progenitor cell transplantation from two HLA-mismatched healthy fathers to
      two infants with severe aplastic anemia.
AB  - Pluripotent stem cells of hematopoiesis are included among CD34+ cells in the
      blood and bone marrow. After granulocyte-colony stimulating factor (G-CSF)
      mobilization, 1-2% of the mononuclear cells in the blood are CD34+ cells, which
      can be obtained by leukapheresis. We performed CD34+ progenitor cell
      transplantation in two children with severe aplastic anemia (SAA) who lacked HLA
      matched donors. The donors were treated with G-CSF, 600 micrograms/body/day
      subcutaneously, for 4-5 days. CD34+ cell selection was performed from the
      apheresis concentrate with mouse anti-CD34 antibody 9C5 and magnet beads coated
      with sheep anti-mouse IgG1. After the transplantation, the patients received
      tacrolimus to prevent graft-versus-host disease (GVHD). G-CSF was given to both
      patients. A mean number of 4.96 x 10(6) CD34+ cells per kilogram of body weight
      were transplanted. The hematopoietic recovery after the CD34+ cell
      transplantation was rapid, except for platelets, and acute GVHD was less than or
      equal to grade I. Case 1, who demonstrated mixed chimerism, anemia and
      thrombocytopenia after the graft, received a second transplant with intensified
      preconditioning, and now sustains complete and stable hematopoiesis after a
      follow-up of 314 days posttransplant. Although Case 2 showed early rejection and
      received a second transplant, sustained engraftment was never achieved. However,
      the patient's own hematopoiesis appeared. For SAA patients who do not have HLA
      matched donors, this type of approach seems to be a feasible and useful method.
      However, an intensified preconditioning regimen to overcome the high likelihood
      of rejection should be employed.

PMID- 9594441
TI  - Progression from myelodysplastic syndrome with monosomy 7 to acute monoblastic
      leukemia with MLL gene rearrangement.
AB  - We report a case of myelodysplastic syndrome (MDS) with the 11q23 translocation
      at its leukemic transformation. Southern blot analysis demonstrated that the MLL
      gene on chromosome 11 was rearranged during the progression from MDS to acute
      leukemia. The clinical observation in this case supports the notion that leukemic
      transformation involves multiple cytogenetic evolutionary progresses, and that
      MLL gene rearrangement corresponds to the final step of leukemogenesis.

PMID- 9594442
TI  - Recombinant adeno-associated virus-mediated gene transfer into human leukemia
      cell lines.
AB  - Adeno-associated virus (AAV)-based vector is a promising gene transfer vehicle by
      virtue of the characteristics of wild-type AAV:tropism to a wide range of human
      tissues and locus-specific integration at chromosome 19q13.3. To elucidate the
      nature of the recombinant AAV (rAAV), transduction of neomycin phosphotransferase
      enzyme gene (NeoR gene) into seven human leukemia cell lines was performed.
      Transduction efficiencies were assessed by colony formation assay and limiting
      dilution assay. The results suggested that both assays are comparable.
      Transduction efficiencies of the NeoR gene into K-562, MEG-O1, Raji, MOLT-3, HL
      60, U937 and NKM-1 at a multiplicity of infection (MOI) of 0.1 were 0.27, 0.25,
      0.015, 0.009, < 0.0025 and < 0.0025%, respectively. After purification and
      concentration of rAAV, 27% efficiency was observed in K562 at an MOI of 7 and a
      linear relationship between MOI and efficiency was confirmed, suggesting that
      this system may be useful for gene transduction into leukemia cells. Integration
      of the NeoR gene into the host genome was detected by Southern blotting analysis,
      which showed various sizes of digested fragments. A fluorescent in situ
      hybridization (FISH) study was carried out on 11 clones, in all of which the NeoR
      gene was integrated out of chromosome 19q13.3. In five of the clones, whole
      chromosome painting probes revealed that the integration sites were chromosomes
      1q, 2q, 2q, 11p, 12p and 13q.

PMID- 9594443
TI  - Pregnancy among long-term survivors of acute leukemia. A second nationwide
      survey.
AB  - A second nationwide survey was conducted to determine the outcome of pregnancy in
      long-term survivors of acute leukemia and to clarify the influence of treatment
      on the offspring of long-term survivors. In July 1996, 336 survey responses were
      received from the 498 Japanese institutions surveyed. A total of 89 cases (39
      spouses of male patients and 50 female patients) who had babies during their
      first remission were analyzed, including 43 patients from the first survey in
      1991. Median age at the birth of first baby was 30.7 years for male patients and
      28.6 years for female patients. A total of 109 of the 117 pregnancies resulted in
      live births and eight resulted in abortions. A total of 58 cases had single
      children and 23 cases had two or more, generally from separate pregnancies, but
      including two pairs of twins. The infant was male in 59 cases, female in 37 and
      gender was not reported in 13 cases. Ages of children ranged from 2 months to 20
      years at the time of this study and all children were in good health. There were
      two minor anomalies, both of which were surgically corrected. Of the 81 parents
      bearing live infants, 75 remained in complete remission. Five fathers died (four
      of relapse and one of another disease). In conclusion, there was no apparent
      increase in pregnancy complications or congenital anomalies in the children of
      long-term survivors with acute leukemia.

PMID- 9594444
TI  - Characterization of leukemic cells in CD2/CD19 double positive acute
      lymphoblastic leukemia.
AB  - In the diagnosis of leukemia, CD2 which is a T-cell associated marker and CD19
      which is a B-cell associated marker are widely used to determine the lineage of
      leukemic cells. It is known that the cells of acute lymphoblastic leukemia (ALL)
      express both CD2 and CD19 in some cases. The origins of these cells are generally
      thought to be a common precursor for T- and B-lymphocytes. However, cytoplasmic
      staining of CD3 which is a more specific marker for T-lineage and cytoplasmic
      staining of mb-1 (CD79a) which is more specific for B-lineage were not performed
      in previous reports and the determination of the cell lineages of these cells was
      unclear. We had two cases of ALL whose blasts were CD2/CD19 double positive. The
      first case was assessed as B-lineage because the cells expressed cytoplasmic
      CD79a and lacked cytoplasmic CD3. The immunoglobulin (Ig) heavy chain gene was
      rearranged. The other cell surface markers including CD22 and HLA-DR also
      suggested that these cells were B-lineage. The CD2 expression may be a
      coincidence and should not be taken as a T-cell marker in this case. It was
      difficult to determine the lineage in the second case because both cytoplasmic
      CD79a and cytoplasmic CD3 were expressed and neither TCR beta chain nor Ig heavy
      chain genes were rearranged. The other surface markers were not useful to
      determine the lineage. We concluded that this case was really an unclassified
      ALL. Accordingly, cytoplasmic staining of CD3 and CD79a should be carried out in
      the diagnosis of leukemia when it is difficult to determine the cell lineage.

PMID- 9594445
TI  - Differential effect of tumor necrosis factor-alpha on thrombomodulin gene
      expression by human monocytoid (THP-1) cell versus endothelial cells.
AB  - Human mononuclear phagocytes (MO) express a functional form of thrombomodulin
      (TM), the anticoagulant molecule typically considered purely in the context of
      regulation of conversion of protein C (PC) to activated PC (aPC) by thrombin
      bound TM at the endothelial cell surface. We have been interested in the anti
      inflammatory actions of aPC, including its ability to suppress MO production of
      multiple pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1 (IL-1), leading us to consider whether MO surface
      expression of TM and resultant local aPC generation, might contribute to
      autoregulation of MO activation at sites of inflammation involving thrombin and
      fibrin formation. Since TNF-alpha and IL-1 are known to downregulate endothelial
      expression of TM, this study investigated the effects of TNF-alpha on production
      of TM by the monocytic leukemic cell line, THP-1. THP-1 cells display many
      monocyte-like properties, providing a convenient source for biochemical and
      molecular studies. Western blotting of lysates of THP-1 cells versus cultured
      human umbilical vein endothelial cells showed that after 24 h of stimulation, TNF
      alpha decreased TM protein expression in endothelial but not THP-1 cells and
      comparable responses were noted by flow cytometry. Subsequent Northern blot
      analysis showed that at 24 h, TNF-alpha diminished TM steady state mRNA in
      endothelial but not THP-1 cells, although Northern analysis of the kinetics of TM
      steady state mRNA did show a rapid and transient modulation by TNF-alpha at 2 h
      of stimulation, which was confirmed by nuclear run-on analysis of the effect of
      TNF-alpha on TM gene transcription rates in THP-1 cells, analysis of protein
      expression by flow cytometry and Western blotting showed similar effects. In
      contrast to the divergent effects of TNF-alpha on THP-1 vs endothelial cells,
      agonists such as cyclic adenosine monophosphate (c-AMP) and phorbol ester (PMA)
      had comparable effects on THP-1 and endothelial cells, resulting in parallel
      increases or decreases in TM mRNA and protein expression, respectively. Hence,
      there is a 'split' in the nature of endothelial vs THP-1 cellular responses to
      TNF-alpha as compared to non-inflammatory stimuli, suggesting cell-specific
      differences in regulation of the TM promoter. We conclude that in contrast to its
      effects on TM expression by endothelial cells, exposure of THP-1 cells to TNF
      alpha causes a rapid and transient decrease in TM mRNA production which is
      followed by sustained and high level expression, supporting the concept that MO
      expression of TM may contribute to regulation of MO activation and cytokine
      production at inflammatory sites.

PMID- 9594446
TI  - Interferon-alpha treatment of acute lymphoblastic leukemia relapse after
      unrelated bone marrow transplantation.
AB  - A 32-year-old Japanese male in his second remission of acute lymphoblastic
      leukemia (ALL) received a matched unrelated donor bone marrow transplant (BMT)
      from the Japan Marrow Donor Program. On day +83, a bone marrow examination
      revealed 5.2% leukemic cells. Despite the cessation of cyclosporine, leukemic
      cells in the bone marrow increased to 18.4% on day +91. Treatment was started
      with interferon (IFN)-alpha-2b 3 x 10(6) U/body s.c. daily on day +92 and
      leukemic cells in the bone marrow disappeared completely. The toxicity of IFN
      alpha treatment included leukoencephalopathy consisting of somnolence,
      disorientation, short-term memory loss, lack of coordination and ataxia,
      myelotoxicity requiring multiple platelet transfusions and exacerbation of graft
      versus-host disease (GVHD) of oral cavity, skin and lung. Because of progressive
      GVHD, IFN-alpha was discontinued on day +124. On day +132, a bone marrow aspirate
      showed 6.4% leukemic cells. The patient died of progressive ALL on day +178. IFN
      alpha may be useful for the treatment of leukemic relapse following BMT, although
      its toxicity is marked.

PMID- 9594447
TI  - Cold agglutinin disease by autoanti-i blood type antibody associated with B cell
      chronic lymphocytic leukemia.
AB  - Cold agglutinin (CA) disease is a rare complication of B cell chronic lymphocytic
      leukemia (CLL). We report a case of CA disease by autoanti-i blood type antibody
      associated with CD5-negative CLL. The specificity of cold agglutinin in the sera
      and eluates from red blood cells were analyzed by reactivity against panels of
      red blood cells and also hemagglutinin inhibition assay using
      lactonorhexaosylceramide, and were determined to be an anti-i blood group
      antibody of the monoclonal IgM kappa isotype. PCR analysis of immunoglobulin
      heavy-chain genes from bone marrow-derived genomic DNA showed CLL cells utilizing
      DP-54 as a VH gene, differing from the reported VH genes used for cold agglutinin
      with anti-I/i specificity. The anti-i antibody in this patient might be
      secondarily produced by residual B cells due to an immunodysregulatory state, and
      not from CLL cells.

PMID- 9594448
TI  - Detection of t(8;14)(q24;q32) by polymerase chain reaction for long DNA targets:
      a report of two patients with B-cell non-Hodgkin's lymphoma.
AB  - We developed a novel technique for long-distance polymerase chain reaction (LD
      PCR) to detect t(8;14)(q24;q32). LD-PCR can amplify up to 12 kb of DNA
      encompassing the c-MYC and constant regions of the immunoglobulin heavy chain
      gene. In this report, we present two patients with B-cell non-Hodgkin's lymphoma.
      Clinical materials obtained from these patients were examined by LD-PCR. One
      patient had small noncleaved cell lymphoma (case 1) and the other had diffuse
      large cell lymphoma (case 2). Both patients showed central nervous system
      involvement. LD-PCR using appropriate primer pairs and a newly available Taq
      polymerase for longer product synthesis detected a 9.6 kb (case 1) and a 2.4 kb
      (case 2) c-MYC/C gamma fusion product indicative of t(8;14) in all materials in
      which lymphoma cells were shown positive by microscopic examination. LD-PCR
      provides an advantage in rapid detection of lymphoma cells carrying t(8;14).

PMID- 9594449
TI  - Dissemination of Epstein-Barr virus associated B-cell lymphoma of the brain after
      development of immunological incompetence with Evans syndrome.
AB  - A 54-year-old female with Epstein-Barr virus (EBV)-associated B-cell lymphoma of
      the brain and Evans syndrome is presented. After treatment of the lymphoma with
      irradiation to the brain and chemotherapy she developed Evans syndrome with
      autoimmune hemolytic anemia and thrombocytopenia. Further immunosuppressive
      treatment for Evans syndrome caused the dissemination of EBV-associated B-cell
      lymphoma. The dissemination of EBV-associated B-cell lymphoma was confirmed by in
      situ hybridization with EBV encoded small RNAs (EBER), polymerase chain reaction
      with Bam HI-W fragment of EBV and lymphocyte determined membrane antigen (LYDMA)
      and immunohistochemistry with latent membrane protein (LMP). Since only a few
      cases of lymphomas associated with EBV occurring during autoimmune diseases have
      been reported, this is an illustrative case.

PMID- 9594450
TI  - Extramedullary hemopoiesis in a patient with beta-thalassemia trait.

PMID- 9594451
TI  - Hematopoietic suppression in a child with human herpesvirus-6 infection.

PMID- 9594452
TI  - A chromosomal alteration of inv(16)(p13q22) as an additional change to
      t(9;11)(p22;q23) in a patient with acute monoblastic leukemia (M5a)

PMID- 9594453
TI  - The Ninth Circuit Court's treatment of the history of suicide by Ancient Jews and
      Christians in Compassion in Dying v. State of Washington: historical naivete or
      special pleading?
AB  - In this article, Prof. Darrel Amundsen critiques Judge Reinhardt's comments
      regarding "Historical Attitudes Toward Suicide" in his Compassion in Dying
      opinion. Amundsen demonstrates that the court's characterization of ancient
      Jewish and Christian practices is inaccurate and misleading because it fails to
      acknowledge the complexities of the moral issue of suicide. Amundsen discusses
      martyrdom, suicide in general, suicide by the ill, and euthanasia in ancient
      Judaism. In contrast to the court's commentary, Amundsen demonstrates that regard
      for human life is a central feature of Jewish ethical monotheism. Furthermore,
      the author challenges the court's conclusions about early Christianity, and
      explains why its treatment of the issue of suicide in early Christianity is
      misleading and inaccurate. Amundsen's discussion of early Christianity includes
      suicide, martyrdom, and especially the Augustinian teaching on suicide. He
      concludes that the court's treatment of the issue of suicide in early
      Christianity is so historically and conceptually muddled as to be fundamentally
      inaccurate.

PMID- 9594454
TI  - Euthanasia in the Commonwealth of Australia.
AB  - This article describes the debate over the euthanasia law of the Northern
      Territory of Australia in its constitutional context. After considering the
      juridical status of the Northern Territory and related topics, this article
      outlines the judicial and legislative challenges to the Rights of the Terminally
      Ill Act (RTI Act) of the Northern Territory and concludes by offering some
      justifications for the passing of the Euthanasia Laws Act 1997 (Commonwealth),
      which effectively repeals the RTI Act. In dealing with these issues special
      emphasis will be given to the problem of Commonwealth law overriding Territory
      law and the concept of fundamental common law rights. The appropriateness of a
      Parliamentary solution--as opposed to a resolution through the courts--is
      defended.

PMID- 9594455
TI  - Dutch court decisions on nonvoluntary euthanasia critically reviewed.
AB  - The author critically reviews Dutch court decisions on nonvoluntary euthanasia.
      First, he examines euthanasia practice in the Netherlands. The author next
      discusses in detail the 1995 cases of two physicians who were prosecuted for
      terminating the lives of infants who were severely ill and disabled. The courts
      accepted nonvoluntary euthanasia and relied on the physicians' defense of
      necessity. Jochemsen exposes serious flaws in the reasoning of the courts and
      concludes that newborns with congenital disorders should be given appropriate
      palliative care. Jochemsen fears that by extending the practice of euthanasia to
      infants with disabilities the Dutch courts have taken another step toward
      endangering the lives of all incompetent persons.

PMID- 9594456
TI  - Christopher John Wake and Djiniyini Gondarra v. Northern Territory of Australia
      and the honorable Keith John Austin Asche AC QC the Administrator of the Northern
      Territory of Australia No. 112 of 1996.

PMID- 9594457
TI  - Medicare update.

PMID- 9594458
TI  - Sacred trust.

PMID- 9594459
TI  - Health profession or beauty business: what direction is dentistry taking?

PMID- 9594460
TI  - Health profession or beauty business: what direction is dentistry taking?

PMID- 9594461
TI  - The TMD controversies.

PMID- 9594462
TI  - The CDA and evidence-based care.

PMID- 9594463
TI  - A teamwork approach.

PMID- 9594464
TI  - Drug-induced gingival enlargements.
AB  - There are many types of gingival enlargements which vary according to the
      etiologic factors and pathologic processes that produce them. The most common
      drug-induced gingival enlargement is associated with Dilantin (phenytoin).
      Cyclosporin and calcium channel blockers, which are increasingly used for some
      cardiac diseases, immunosuppression and autoimmune disorders, also cause gingival
      enlargement. The term "gingival hyperplasia" is an inappropriate term because
      enlargement is not the result of an increase in the number of cells, but rather
      an increase in extracellular tissue volume. This paper presents a detailed
      description of various drug-induced gingival enlargements, including the clinical
      appearance, microscopic presentation, pathogenic mechanisms and treatment
      options.

PMID- 9594465
TI  - Scaling and root planing: hand versus power-driven instruments.
AB  - Scaling and root planing (S&RP) are regarded as the main modalities for treating
      periodontal disease. The goal of these treatments is to arrest the disease
      process, maintain a healthy periodontium and preserve the dentition. As
      prevention becomes a larger component of everyday dental practice, dentists are
      performing S&RP more often as part of their periodontal maintenance programs.
      Therefore, it is essential for dentists to know the latest S&RP techniques and
      methods. This paper reviews the current knowledge and experiences related to
      mechanical non-surgical periodontal therapy and focuses on the types of S&RP
      instruments that are available, their advantages and disadvantages, their
      efficacy in debridement, and their effects on the hard tissues of the oral
      cavity.

PMID- 9594466
TI  - Infective endocarditis: dental implications and new guidelines for antibiotic
      prophylaxis. American Heart Association.
AB  - The American Heart Association (AHA) has developed new guidelines for antibiotic
      prophylaxis for patients at risk of infective endocarditis (IE). These guidelines
      are based on the on-going study of endocarditis cases and continued experience
      with antibiotic prophylaxis, and are an update of the 1990 recommendations. The
      major changes from the 1990 guidelines are: the recognition that most cases of IE
      are not attributable to an invasive procedure; that cardiac conditions may
      present different levels of risk categories; increased delineation of when
      prophylaxis should be given in cases of mitral valve prolapse; a change to a
      single dose of antibiotic and changes in the antibiotics recommended for
      prophylaxis. The revised AHA guidelines parallel those in Europe and the United
      Kingdom. It is essential that all dental professionals be fully aware of the
      modifications to these guidelines because of their importance in patient care and
      their medico-legal implications.

PMID- 9594467
TI  - An update of mechanical oral hygiene practices: evidence-based recommendations
      for disease prevention.
AB  - PURPOSE: This review updates the mechanical oral hygiene practices discussed at a
      1986 State-of-the-Science Workshop. METHODS: The 1984-1995 MEDLINE database was
      searched and appropriate studies that used disease outcome measurements were
      located and selected. Recommendations were made based on the levels of evidence
      concept. RECOMMENDATIONS: 1) There is good evidence to recommend: toothbrushing
      twice daily with fluoridated toothpaste; using oscillating-rotating or counter
      rotational-action electric toothbrushes; flossing for adults; personal
      supragingival irrigation as an adjunct to toothbrushing; and scaling of disease
      active sites for the treatment of periodontal diseases. 2) There is moderate
      evidence to recommend: using any soft-bristled manual toothbrush; using wooden
      interdental cleaners; scaling of disease active sites every three to four months
      for patients with histories of moderate/severe periodontitis; scaling of disease
      active sites at intervals of > or = 6 months for most patients, based on patient
      need; and removal of restoration overhangs. 3) There is moderate evidence to not
      recommend: use of vibrating, rotating or sonic action electric toothbrushes;
      using foam brushes; flossing for children; using interdental brushes; gingival
      massage; and tongue brushing or scraping. 4) There is good evidence to not
      recommend: subgingival scaling for patients with no signs of active disease; and
      polishing for disease prevention. CONCLUSIONS: Consistent with the 1986 workshop
      report, the 1996 recommendations emphasize the importance of personal oral
      hygiene and the provision of professional treatment when personal care fails to
      prevent disease.

PMID- 9594468
TI  - Guidelines on the use of space maintainers.

PMID- 9594469
TI  - Dental education.

PMID- 9594470
TI  - Hygiene's competitive challenge to dentistry.

PMID- 9594472
TI  - Update on the nomenclature of carbohydrates and their dental effects.
AB  - OBJECTIVES: This review aims to clarify the nomenclature of carbohydrates,
      including novel manufactured carbohydrates which are becoming increasingly
      popular within the food industry, and to summarise what is known about the
      effects of different carbohydrates on dental health. DATA SOURCES: This review
      compiles information from articles published in mainstream microbiological,
      nutritional and dental journals that are of relevance to carbohydrates and dental
      health. STUDY SELECTION: The review considers literature on classification of
      carbohydrates by chain length, for example mono-di-oligo- and poly-saccharides
      and classification for dental health purposes, namely intrinsic, non-milk
      extrinsic sugars. This paper includes a comprehensive review of information on
      novel carbohydrates including isomaltosaccharides, fructo-oligosaccharides and
      gluco-oligosaccharides, maltodextrins and glucose syrups. Information on polyols
      and non-starch polysaccharides is also presented and current knowledge on the
      dental effects of all carbohydrates are discussed. CONCLUSION: There is a wealth
      of information on dietary sugars and the effects of sugars on dental health is
      established knowledge. However, the range of 'novel' manufactured carbohydrates
      which are becoming available for food use is increasing and information regarding
      the cariogenicity of these substances is sparse. Research indicates that
      maltodextrins and glucose syrups are cariogenic, however, initial studies on some
      synthetic oligosaccharides have suggested reduced cariogenicity compared to
      sucrose. Further human plaque pH and in vitro and in vivo tests of cariogenicity
      are required to clarify these initial observations.

PMID- 9594471
TI  - Dental materials: 1996 literature review.
AB  - This critical review of the published literature on dental materials for the year
      1996 has been compiled by the Dental Materials Panel of the UK. It continues the
      series of annual reviews started in 1973 and published in the Journal of
      Dentistry. Emphasis has been placed upon publications which report upon the
      materials science or clinical performance of the materials. The review has been
      divided by accepted materials classifications (fissure sealants, glass
      polyalkenoate cements, dentine bonding, dental amalgam, endodontic materials,
      casting alloys, resin-bonded bridges and ceramo-metallic restorations, ceramics,
      denture base resins and soft lining materials, impression materials, implants
      materials, orthodontic materials, biomechanics and image processing, resin
      composites and casting investment materials and waxes). Three hundred and
      thirteen articles have been reviewed.

PMID- 9594474
TI  - Postobturation pain after single- and multiple-visit endodontic therapy. A
      prospective study.
AB  - OBJECTIVES: This prospective study was conducted to determine whether there is
      any significant difference in the incidence of postobturation pain after single-
      and multiple-visit root canal treatment (RCT). METHODS: The frequency of
      postobturation pain was recorded and evaluated over an observation period of 30
      days in 291 of 300 consecutive patients receiving RCT. The patients were assigned
      randomly and consecutively into either single- or multiple-visit groups. The
      canals of all teeth were prepared and filled by a single operator using the step
      back and lateral condensation techniques. The data were analysed statistically to
      determine the relationship, if any, between the pain experienced and pulpal
      vitality, tooth type, pre-operative pain, and the sex and age of the patient.
      RESULTS: Nine of the 300 patients were excluded from the analysis as they failed
      to attend for postoperative reviews. A significantly higher incidence (P < 0.01)
      of postobturation pain was found in the multiple-visit group (38%) than in the
      single-visit group (27%) within 24 h of obturation. The incidence of pain
      decreased thereafter, with all patients being sysmptom free at the end of the
      observation period. No significant correlation was found between postobturation
      pain and any other factor, with the exception that teeth which had nonvital pulp
      prior to treatment were associated with a significantly greater (P < 0.005)
      incidence of postobutration pain. CONCLUSIONS: Pain was significantly higher in
      the multiple-visit RCT group and significantly associated with the treatment of
      the nonvital pulp.

PMID- 9594473
TI  - Fired ceramic inlays: a 6-year follow up.
AB  - OBJECTIVES: The aim of this study was to evaluate feldspathic ceramic inlays
      luted with dual-cured resin composite or glass polyalkenoate (ionomer) cement
      (GIC) during a 6-year follow-up. METHODS: One-hundred and eighteen Class II fired
      feldspathic ceramic inlays were placed in 50 patients. In each patient half of
      the inlays were luted with a dual-cured resin composite and the other half with a
      conventional glass ionomer cement. The inlays were evaluated clinically,
      according to modified USPHS criteria, at baseline, after 6 months and then
      annually over a 6-year period. RESULTS: Of the 115 inlays evaluated at 6 years,
      12% in the resin composite group and 26% in the GIC group were assessed as having
      failed. The main reason for failure in both groups was partial fracture or total
      loss of the inlays. Secondary caries was found to be associated with three inlays
      in one high caries risk patient. One inlay was replaced because of postoperative
      sensitivity. CONCLUSION: A relatively high and increasing failure rate was
      observed over the 6-year period of the study. The failure rate was more
      pronounced in the GIC group.

PMID- 9594475
TI  - Effect of 6-monthly applications of chlorhexidine varnish on incidence of
      occlusal caries in permanent molars: a 3-year study.
AB  - OBJECTIVES: The aim of this study was to assess the effect of a chlorhexidine
      varnish on occlusal caries incidence when applied 6-monthly into the fissures of
      erupting and freshly erupted permanent molars. METHODS: In a double-blind
      clinical trial, 332 children aged 5/6 and 11/12 years attending a Child Dental
      Health Centre were randomly assigned to a control and an experimental group.
      Criteria for inclusion in the study were that all first permanent molars in 5-6
      year-olds and all second permanent molars in 11-12-year-olds either had recently
      erupted, or were in a stage of eruption, or would erupt within half a year. At
      baseline, counts of dmfs/DMFS and mutans streptococci in saliva were recorded.
      During a maximum of 3 years, every 6 months the occlusal surfaces of molars in
      the experimental group received a 40% chlorhexidine varnish application, whereas
      those in the control group received a placebo varnish application. RESULTS: Data
      of 316 children were analysed and ANOVA showed no significant occlusal caries
      reduction in this sample of Dutch 5/6- and 11/12-year-old children. After
      stratification into low and high caries risk groups, a statistically significant
      caries-reducing effect on occlusal caries in permanent molars was found in the
      group of children with > or = 10(6) mutans streptococci per ml saliva (P < 0.05).
      CONCLUSION: Six-monthly application of chlorhexidine varnish has no caries
      reducing effect on occlusal caries in recently erupted permanent molars in a
      population with low caries prevalence.

PMID- 9594476
TI  - A survey of the efficiency of visible light curing units.
AB  - OBJECTIVES: The purpose of this study was to survey the efficiency of visible
      light curing units in dental practices across Australia. METHODS: Survey forms
      were distributed to representatives of 3M Health Care to complete when visiting
      dentists in their working areas. The information collected included the type and
      age of the unit, curing times used, history of maintenance, replacement of
      components, and the light intensity reading. RESULTS: Of the 214 light curing
      units surveyed, approximately 27% recorded a light intensity of 200 mW cm-2 or
      less, a level regarded as inadequate to cure a 2-mm thick increment of composite
      resin. An additional 26% registered an output of between 201 and 399 mW m-2. This
      level would be considered acceptable with additional curing time; however, 44% of
      practitioners were curing for 20 s or less. A negative correlation was found
      between the age of the unit and the intensity recorded. Nearly 50% of respondents
      had never checked the light output of their unit. CONCLUSIONS: The results
      indicate that just over one-half of the light curing units surveyed were not
      functioning satisfactorily. An obvious reduction in intensity was noted with the
      older units. There is a substantial lack of awareness among dentists of the need
      for maintenance and regular checking of the light intensity of these units.

PMID- 9594477
TI  - Bonding to alumina ceramic in restorative dentistry: clinical results over up to
      5 years.
AB  - OBJECTIVES: The purpose of this clinical pilot study was to evaluate the resin
      bond to alumina ceramic in vivo when using a bonding method which had been shown
      to be successful in laboratory testing. METHODS: Seventeen resin-bonded all
      ceramic bridges and splints fabricated from a glass-infiltrated alumina ceramic
      were tribochemically silica coated and resin bonded to their abutment teeth. The
      patients were recalled every 6 months to evaluate the restorations with regard to
      function and possible failures. RESULTS: Over a mean observation time of 3.8 +/-
      1.6 years some ceramic fractures occurred. However, the resin bond between the
      teeth and the alumina ceramic always remained stable. CONCLUSIONS: Silica coating
      of alumina ceramic resulted in a durable resin bond over up to 5 years.

PMID- 9594478
TI  - Stress-strain and thermal expansion characteristics of a phosphate-bonded
      investment mould material for dental super plastic forming.
AB  - OBJECTIVES: The stress-strain and thermal expansion characteristics of a
      phosphate-bonded investment material were measured to determine its suitability
      as a die material for superplastic forming of dental appliances. Titanium alloy
      denture bases and implant superstructures have been fabricated successfully using
      this investment material, but a greater understanding of its properties was
      sought to optimize the forming technique before exploitation could proceed. The
      effect of a boron nitride powder on the properties of phosphate-bonded investment
      was also investigated. METHODS: Three-point bend test specimens were cast in the
      phosphate-bonded investment material. Four groups of test samples were produced
      at specified water-to-powder ratios (w/p ratios). For one group 5 wt.% boron
      nitride powder was added to the investment powder before mixing with water. For
      stress-strain measurements specimens were heated to 920 degrees C and held for 30
      min prior to the application of load. For thermal expansion measurements specimen
      length was measured for the entire heating and cooling cycle. RESULTS: Curves of
      stress versus strain and thermal expansion were recorded for all four test
      groups. For increasing initial w/p ratio failure stress decreased with lowest
      failure stresses for specimens containing boron nitride. Strain to failure also
      decreased with increasing initial w/p ratio, except for the group containing
      boron nitride which showed relatively large elongations to fracture. Specimen
      surfaces with higher initial w/p ratios were observed to have larger surface
      porosity. Thermal expansion curves for three groups were very similar, but
      differed considerably from the group containing boron nitride. CONCLUSIONS: The
      lowest initial w/p ratio should be used for highest hot strength. Hot deformation
      of phosphate-bonded investment dies for superplastic forming is an issue that
      requires further investigation because of potential die deformation and the
      resulting loss of fit between the superplastic superstructure and implant
      components. Boron nitride could be used in phosphate-bonded investment to
      decrease thermal expansion, but the consequences of reduced hot strength and
      increased strain to failure may make the modified material unsuitable as a die
      for superplastic forming.

PMID- 9594480
TI  - Antibacterial activity of dentine primer containing MDPB after curing.
AB  - OBJECTIVES: A monomer methacryloyloxydodecylpyridinium bromide (MDPB) has
      antibacterial activity before polymerization. Furthermore, the antibacterial
      agent is immobilized by the polymerization of MDPB and the resin-based material
      incorporating MDPB is able to show an antibacterial effect even after being
      cured. The purpose of this study was to investigate the antibacterial effect of a
      dentine primer containing MDPB after curing. METHODS: The inhibitory effect of a
      cured MDPB-containing primer on the growth of Streptococcus mutans, Actinomyces
      viscosus and Lactobacillus casei was determined by the agar-disc method. The
      bactericidal activity of cured primer during a 1-h contact period was assessed
      using S. mutans, and the elution of unpolymerized MDPB was measured with high
      performance liquid chromatography. RESULTS: Cured MDPB-containing primer showed
      an inhibitory effect on the growth of all species which were in contact with the
      specimen surface, and displayed a little bactericidal effect on S. mutans without
      releasing any unpolymerized antibacterial components. CONCLUSION: Incorporation
      of antibacterial monomer MDPB into dentine primer is beneficial for providing
      antibacterial activity after curing.

PMID- 9594479
TI  - A comparison of fluoride release from various dental materials.
AB  - OBJECTIVE: The aim of this study was to determine, in vitro, the relative short-
      and long-term fluoride release from four resin-modified glass ionomers (Fuji II
      LC, Vitremer, Enforce & Advance), a polyacid-modified composite resin (Dyract
      compomer) and a bonding agent (OptiBond). METHODS: All the materials were
      prepared as outlined by the manufacturers. Circular discs of the materials
      mentioned were suspended in water for up to 300 days and the non-cumulative 24-h
      fluoride release was determined potentiometrically at chosen times. RESULTS: The
      amounts of fluoride released during the first day were Vitremer (1.46 micrograms
      mm-2), Advance (1.18 micrograms mm-2), Fuji (1.08 micrograms mm-2), Optibond
      (0.33 microgram mm-2), Dyract (0.31 microgram mm-2) and Enforce (0.15 microgram
      mm-2). After the second day the sequence changed slightly and remained
      approximately the same for the rest of the 300-day period. There was also an
      increase in the fluoride release during the 60-200-day period relative to the
      previous period. CONCLUSION: In general the most fluoride was released by Advance
      and not by Fuji II LC or Vitremer. For most materials, fluoride is still released
      after 300 days. Furthermore, even a thin layer of bonding agent released a
      relatively high amount of fluoride (volume-wise the most) at the beginning. It is
      deduced that even the release of relatively low amounts of fluoride may result in
      significant concentrations of fluoride in a microleakage gap.

PMID- 9594481
TI  - 'Allergies' article needs updating.

PMID- 9594482
TI  - Variability key to health.

PMID- 9594483
TI  - Coming full circle: osteopathic manipulative treatment and immunity.

PMID- 9594485
TI  - Exercise-induced asthma.
AB  - Exercise-induced asthma is the phenomenon of transient airflow obstruction,
      typically 5 to 15 minutes after physical exertion. The increased airway
      resistance produces a 15% or greater decrease in the forced expiratory volume in
      1 second, or in peak expiratory flow rate. Exercise-induced asthma occurs in 90%
      of individuals with asthma, representing 12% to 15% of the population world-wide.
      The prevalence of exercise-induced asthma among athletes ranges between 3% and
      11%. Several theories of the etiology exist: respiratory heat or water loss (or
      both), hyperventilation causing discharge of bronchospastic chemical mediators or
      rebound rewarming of the blood in airway tissues. Treatment is either by
      pharmacologic or nonpharmacologic means, but medication continues to be the
      cornerstone of therapy for exercise-induced asthma. beta 2-Specific agonists
      remain the drugs of choice. Cromolyn sodium and nedocromil sodium are
      alternatives to the beta 2-agonists, and the combined use of the two classes of
      agents can provide additive benefits.

PMID- 9594486
TI  - Salmeterol: a long-acting beta 2-agonist.
AB  - Salmeterol xinafoate is a potent and highly selective beta 2-adrenoreceptor
      agonist with a duration of action greater than 12 hours. When inhaled twice daily
      in the management of chronic asthma, it results in improved lung function,
      reduces acute asthmatic exacerbations, and improves the patient's quality of
      life. This agent has shown particular benefit for patients who continue to have
      symptomatic asthma despite the regular use of inhaled corticosteroid therapy and
      the frequent use of a short-acting beta 2-agonist. Although there is some
      evidence that salmeterol induces some tolerance to the bronchoprotective effect
      of beta 2-agonist therapy, improvement in lung function and asthma symptoms
      scores, during both the daytime and nighttime, are sustained. Importantly,
      patients must be educated in the proper use of salmeterol; for many asthmatics,
      this medication should be administered with inhaled or oral corticosteroid
      therapy, and salmeterol should not be used for rescue bronchodilation. When used
      properly, salmeterol is an effective and safe adjunctive therapy in the
      management of chronic asthma in adolescents and adults.

PMID- 9594487
TI  - [Evaluation of brain tumor by 99mTc-MIBI: comparison study with 201Tl and
      predictivity of therapeutic effect].
AB  - We compared the detectability of 99mTc-MIBI and 201Tl-chloride for brain tumor in
      relationship with histopathology. We also evaluated correlation between
      therapeutic effect using ACNU, Cisplatine and the degree of MIBI tumor uptake.
      The subjects were 31 brain tumor histologically confirmed by operation or biopsy.
      Dual-isotope SPECT technique was performed at both 20 min and 180 min after
      tracer injection. A tumor to normal lung ratio on both early (ER) and delayed
      image (DR) and retention index (RI) were calculated. The positive rates of 99mTc
      MIBI (90.3% and 77.4%) were comparable to that of 201Tl (90.3% and 80.6%). In the
      relationship with histopathology, both MIBI and Tl accumulated in 100% of
      glioblastoma (GBM), metastasis (meta), anaplastic astrocytoma and 25% of low
      grade astrocytoma on both early and delayed images. On semiquantitative analysis,
      there were no statistical significance among GBM, meta and anaplastic astrocytoma
      of ER, DR, RI in the both radiopharmaceuticals. However, both ER and DR in GBM
      tended to be higher than those of anaplastic astrocytoma. In spite of intense
      MIBI uptake, GBM patients died within six months except one patient. We concluded
      that MIBI can be helpful in detecting brain tumor as Tl. MIBI also might be
      useful in estimating the degree of malignancy in glioma. However, intense MIBI
      uptake did not mean favorable therapeutic effect in patients with GBM treated
      with ACNU and Cisplatine.

PMID- 9594488
TI  - [A comparative study of imaging of myocardial perfusion with 201Tl-SPECT and
      13NH3-PET: visual and quantitative evaluation].
AB  - We compared the results of visual and quantitative evaluation of imaging of
      myocardial perfusion with 201Tl-SPECT and 13NH3-PET in the 7 non-myocardial
      infarction (non-MI) and 42 myocardial infarction (MI) patients. On the 201Tl
      SPECT and 13NH3-PET imaging, the degree of accumulation of each radioisotope (RI)
      was visually classified into four grades of defect score. The percentage of
      uptake was also quantitatively evaluated. RESULTS: In the 7 non-MI patients, NH3%
      uptake in the lateral wall was significantly lower than in the septum, and in the
      lateral wall NH3% uptake was significantly lower than Tl% uptake. For the 42 MI
      patients, segmental defect scores (DS) on 201Tl-SPECT were compared with those on
      13NH3-PET, and a high degree of concordance in DS was found for all territories
      of the left ventricle, antero-septum MI and inferior MI territories. Average Tl%
      uptake/NH3% uptake was near 1, a highly positive correlation was found between
      Tl% uptake and NH3% uptake in all territories of the left ventricle and antero
      septum MI territories, and Tl% uptake/NH3% uptake was larger than 1, but, a
      significant positive correlation existed between Tl% uptake and NH3% uptake in
      the territory with inferior MI. CONCLUSION: These findings indicate that results
      of 201Tl-SPECT imaging were similar to those of 13NH3-PET in evaluation of
      myocardial perfusion in the antero-septum and inferior. However, a difference in
      distribution was observed between 201TlCl and 13NH3 in the lateral wall,
      indicating that particular attention should be paid to the results of imaging of
      myocardial perfusion in the lateral wall.

PMID- 9594489
TI  - [Two cases of two-year-old girls with hypoxic ischemic encephalopathy induced by
      convulsive status].
AB  - We reported two cases of two-year-old girls with hypoxic ischemic encephalopathy.
      Their symptom was coma induced by seizures with respective factors. CT image on
      subacute stage showed the decreased density of the whole brain except for the
      primary sensorimotor cortex and the occipital lobe. MRI and CT images on chronic
      stage revealed generalized atrophy with no abnormal density areas. 99mTc-ECD
      SPECT on chronic stage showed low perfusion in the whole brain except for the
      primary sensorimotor cortex and the occipital lobe, in which areas brain tissue
      is considered to be injured easily in hypoxic ischemic encephalopathy. The
      paradoxical distribution of abnormal cerebral perfusion areas in our cases was
      reported in this paper.

PMID- 9594490
TI  - [A study on accuracy of rCBF measurements loaded with acetazolamide based on the
      microsphere model using iodine-123-IMP SPECT].
AB  - We studied the accuracy of the method for measuring regional cerebral blood flow
      (rCBF) loaded with acetazolamide based on the microsphere model using iodine-123
      IMP (IMP) SPECT. Two methods were examined, the super-early microsphere method
      with continuous withdrawal of arterial blood using the SPECT image obtained 5 min
      after tracer injection and the early microsphere method with one-point arterial
      sampling using the SPECT image obtained 30 min postinjection. On five subjects,
      after acetazolamide administration we measured rCBF by the analysis based on the
      two-compartment model using the data derived from dynamic SPECT scans and the
      sequential arterial blood sampling after IMP injection. Values of rCBF obtained
      by both super-early microsphere method and early microsphere method were
      significantly correlated with those obtained by the two-compartment model
      analysis (r = 0.982, 0.930, respectively). We conclude that it is possible to use
      the method based on the microsphere model in measuring rCBF loaded with
      acetazolamide. The early microsphere method with one-point sampling should be
      used clinically because of its simplicity and less-invasiveness.

PMID- 9594491
TI  - [Nuclear medicine applications in HIV/AIDS].
AB  - Acquired immunodeficiency syndrome (AIDS) is now believed to be an uncurable
      disease despite significant advances in the area of antiretroviral therapy for
      patients with HIV infection. In Japan, it is essential to realize AIDS-defining
      diseases, particularly because it is not until HIV-infected patients are found
      that AIDS manifestations develop. Some of the opportunistic infections and AIDS
      related tumors are curable by earlier diagnosis and treatment, so that nuclear
      medicine plays the major role in diagnosing and monitoring AIDS-defining
      diseases. AIDS complications were correlated with CD4+ lymphocyte counts and
      utility of nuclear medicine in HIV/AIDS was stressed.

PMID- 9594492
TI  - [The relationship between the pathways of the lymphatic drainage into the
      mediastinal nodes and the survival rate for N2 lung cancers underwent curative
      resection].
AB  - The pathways of the metastases to the mediastinal nodes were determined in each
      case of 68 N2 lung cancer patients undergoing mediastinal lymph node dissection.
      The relationship between the pathways of the metastases and the survival rate was
      examined in the 57 N2 lung cancer patients undergoing curative resection. The
      results were as follows: (1) The direct metastatic passage to the mediastinal
      nodes was observed in 32.1% in the right upper lobe. The survival rate of this
      group was 55.4% (4-year survival rate), and that of cases metastasized to the
      intrapulmonary and/or hilar nodes as well as mediastinal nodes was 42.4% (3-year
      survival rate). (2) The dominant lymphatic drainage from the middle lobe and the
      lower lobes flowed into the subcarinal nodes through the hilar nodes. 75% had
      involvement of the subcarinal nodes, and 33.3% had involvement of the upper
      mediastinal nodes. 5-year survival rate of the cases without the upper
      mediastinal nodes metastases was 59.0%, and that of cases metastasized to the
      upper mediastinal nodes was 26.7% (3-year survival rate). (3) The dominant
      lymphatic drainage from the left upper lobe flowed into the subaortic or
      paraaortic nodes. 5-year survival rate in the left upper lobe was 50.0%. It
      suggested that the cases metastasized to the mediastinal nodes via the direct
      passage in the right upper lobe, the cases in the left upper lobe, and the cases
      metastasized to the subcarinal nodes without the upper mediastinal nodes
      metastases in the middle lobe and the lower lobes had better prognosis.

PMID- 9594493
TI  - [Coronary artery bypass grafting to the left circumflex artery in the
      atrioventricular groove].
AB  - Coronary artery bypass graftings were performed to the left circumflex artery
      (LCX) system in the atrioventricular groove (#11 or #13) in addition to
      revascularization to the left anterior descending artery system using
      conventional technique in 10 patients with left main trunk lesion. Distal
      anastomosis was done at #11 of LCX in 6 patients using saphenous vein graft, and
      at #13 of LCX in 4 patients using 2 saphenous vein grafts and using 2 internal
      thoracic artery grafts. The mean flow rate of SVG operated by this technique
      showed larger values than that of SVGs by sequential bypass or individual bypass
      technique to #12 and/or #14 of LCX. Postoperative angiographies showed excellent
      graft patencies and symptomatic improvements were achieved. This technique of
      coronary artery revascularization is recommended and useful in patients whose #12
      and #14 of LCX system is too small to make distal anastomosis.

PMID- 9594494
TI  - [Two cases of complete atrioventricular canal defect whose pulmonary vascular
      resistance were over 10 wood unit.m2 before 6 months of age].
AB  - We report two cases with complete form of atrioventricular canal defect (CAVCD)
      accompanied by Down's syndrome whose pulmonary vascular resistance (Rp) were more
      than 10 Wood unit.m2 at the age of less than 6 months. One child was 3-month-old
      boy whose Rp was 12 Wood unit.m2. The open lung biopsy at 3 months old showed
      histopathological change of Heath-Edwards grade I. He underwent intracardiac
      repair at the age of 4 months. He is doing well at 30 months of postoperative
      period. Another child was 5-month-old girl whose Rp was 15.5 Wood unit.m2.
      Histopathological change of lung at 5 months old demonstrated Heath-Edwards grade
      III. She underwent intracardiac repair at the age of 7 months, 2 months after
      lung biopsy. However, she died of oversystemic pulmonary hypertension and low
      output syndrome 7 days after surgery. The postmortem examination revealed that
      pulmonary vascular obstructive disease progressed during 2 months interval
      between the lung biopsy and the operation. In conclusion, cardiac catheterization
      with estimation of Rp should be performed in the cases of CAVCD, especially in
      those with Down's syndrome, in early infancy. If Rp is more than 10 Wood unit.m2
      and lung biopsy indicates the surgical indication, surgical intervention should
      be done as soon as possible since the pulmonary vascular obstructive disease may
      progress in a short period.

PMID- 9594495
TI  - [Advantages and disadvantages of harmonic scalpel in thoracic surgery].
AB  - We evaluated the usefulness of Harmonic Scalpel in thoracic surgery. Harmonic
      Scalpel is an ultrasonically activated surgical device which can coagulate and
      cut the vessels or tissues. The instrument made thoracoscopic resection of the
      neurogenic tumor and the mediastinal lymph node and thoracoscopic sympatectomy
      safetier and easier, because it does not conduct an electric current to the nerve
      and has high ability of hemostasis. Harmonic Scalpel will be very useful device
      in the future if its shapes of blades or handpieces are improved.

PMID- 9594496
TI  - [Coronary artery bypass grafting under the excellent heart exposure provided by
      the use of the coronary artery exposing tape].
AB  - We have used the coronary artery exposing tape devised by Akio Matsuura in 93
      patients undergoing coronary artery bypass grafting. We could perform graft
      anastomosis more easily and safely by the use of this tape than by the
      conventional simple compression method of the heart with the gauzes. The heart
      was lifted anteriorly with the rotation by the tape pulled to the left side or to
      the caudal side. The right coronary artery branches were exposed excellently by
      the simple traction of the tape to the caudal side. The circumflex coronary
      artery branches were well exposed by one tape pulled to the left side and another
      tape to the right side over the heart with the counterclockwise rotation of the
      heart. In these procedures no complication was encountered in association with
      the traction of this tape.

PMID- 9594497
TI  - [Traumatic aortic regurgitation: report of two surgical cases].
AB  - Two successful surgical cases with aortic regurgitation due to blunt trauma are
      reported. Case 1: A 48-year-old female was transferred to our hospital after a
      traffic accident. She was intubated and mechanically ventilated. Twelve days
      later, echocardiography demonstrated massive aortic regurgitation. The next day,
      aortic valve replacement was performed using a 21 mm SJM mechanical valve. The
      central part of the non-coronary cusp was torn and perforated 15 mm long. She is
      in good condition three years after surgery. Case 2: A 57-year-old male was
      transferred to the nearest hospital because he was involved in a snowslide
      accident. A month after the injury, catheterization showed massive aortic
      regurgitation and pulmonary hypertension. An aortotomy revealed that the intima
      around the right coronary ostium was completely torn. A perforation with a
      diameter of 3 mm was also observed on the right coronary cusp. After coronary
      cusps were excised, interrupted mattress sutures buttressed with pledgets were
      passed through the aortic wall at the distal level of the intimal laceration and
      then to the aortic annulus. A 25 mm SJM prosthetic valve was seated at the aortic
      ring. As the right coronary ostium was included in the plicated aortic wall,
      aortocoronary bypass was constructed using the great saphenous vein. He is doing
      well 14 months after surgery. Aortic regurgitation due to blunt trauma is rare
      and difficult to diagnose. Sometimes cardiac failure progresses rapidly.
      Therefore, urgent surgery is recommended as soon as the diagnosis is confirmed.

PMID- 9594498
TI  - [Cardiac surgery for the patients with hyperthyroidism].
AB  - Since open heart surgery may cause thyrotoxic crisis during the perioperative
      period in patients with hyperthyroidism, close monitoring and control are needed.
      We performed open heart surgery in 2 patients with hyperthyroidism, and good
      results were obtained. A 71-year-old patient with mitral valve insufficiency
      underwent mitral valve repair by replacement of chordae tendineae with
      polytetrafluoroethylene sutures and annuloplasty with a Duran's Ring. The other
      20-year-old patient with aortic valve insufficiency underwent aortic valve
      replacement with an SJM valve. In the two patients, cardiopulmonary bypass for a
      prolonged period was required during surgery. However, thyrotoxic crisis could be
      prevented by controlling thyroid function by preoperative treatment with anti
      thyroid agents, concurrent medication with Lugol's iodine solution immediately
      before surgery and re-administration of anti-thyroid agents early after surgery.

PMID- 9594499
TI  - [Coronary artery bypass grafting with arterial graft alone: radial artery and
      inferior epigastric artery used in combination].
AB  - We experienced 8 cases in which Coronary Artery Bypass Grafting (CABG) was
      performed by the arterial graft alone with radial artery (RA) and inferior
      epigastric artery (IEA) used in addition to internal thoracic artery (ITA) and
      right gastroepiploic artery (RGEA). All the patients were male ranging in age
      from 50 to 66 years (mean 57.5 year). The number of anastomosis was 3 to 5
      branches (mean 3.6 branches). IEA was anastomosed with LITA and used as a
      composite graft in all cases. As for the proximal anastomosis of RA it was
      anastomosesd with ascending aorta. On postoperative radiography of graft, LITA,
      RITA, IEA and RA were all patent and RGEA was occluded only in one anastomosis
      where it was sequentially used (96.6%). All the patients followed a satisfactory
      postoperative course, and no case developed any major complications. CONCLUSION:
      The use of IEA and RA made it possible to perform CABG using only the artery with
      excellent postoperative results and early patency rate of the graft.

PMID- 9594500
TI  - [Clinical study of synchronous double cancers of the lung and digestive tract].
AB  - Among 64 cases of surgically resected primary lung cancer from 1991 to 1997,
      there were 5 cases of synchronous double cancers of the lung and digestive tract.
      They were consisted of 4 males and 1 female and the patient age at the time of
      the lung resection ranged from 65 to 81 years (average: 74.6). One male was
      diagnosed as having lung cancer (squamous cell carcinoma) along with sigmoid
      colon cancer (adenocarcinoma) and others were lung cancer (adenocarcinoma) and
      gastric cancer (adenocarcinoma). In two patients with early gastric cancer,
      lobectomies were performed following endoscopic resection of gastric cancer. In
      three patients including two old man and woman (over 80 years old), lobectomies
      and gastrectomies (or sigmoidectomy) were performed at the same time. We omitted
      mediastinal lymph nodes dissections in two old patients and no operative
      complications occurred. All patients are alive now. It can be concluded that in
      cases of synchronous double cancers of the lung and digestive tract, we must
      select the best treatment that is not invasive for the patient and that
      simultaneous operation for double cancer can be safely performed.

PMID- 9594501
TI  - [Atrial septal defect and severe pulmonary hypertension in an adult who needed
      nitric oxide inhalation after repair].
AB  - A 51-year-old male was diagnosed as having an ostium secundum atrial septal
      defect with severe pulmonary hypertension. Although pulmonary artery pressure was
      as high as 96/32 and pulmonary vascular resistance was 14.2 U.m2, he underwent
      corrective surgery, because pulmonary to systemic blood flow ratio was 2.0. After
      he regained consciousness in ICU, pulmonary hypertensive crises recurrently
      occurred and the hemodynamics became quite unstable. Administration of
      conventional drugs proved to be ineffective. Since inhalation of low dose (3-4
      ppm) nitric oxide was started, however, his condition was markedly improved and
      he recovered uneventfully thereafter. Two years later, pulmonary artery pressure
      was reduced to 52/28 and pulmonary vascular resistance was 9.9 U.m2. Although
      good outcome can not be expected in all surgically treated cases, we should
      refrain from deciding easily that surgery is contraindicated, because no criteria
      of surgical indication for atrial septal defect with pulmonary hypertension
      appears to be perfect.

PMID- 9594502
TI  - [A case report of mitral valve replacement using a parasternal incision
      (minimally invasive cardiac surgery) with pleuritis tuberculosa and after
      esophagus operation].
AB  - A 68-year-old man underwent mitral valve replacement because of mitral
      regurgitation (prolaps of anterior mitral leaflet) using parasternal incision
      (Delos M. Cosgrove, minimally invasive surgery). He had been treated as pulmonary
      tuberculosis previously and had undergone esophagus operation using stomach role
      reconstruction beneath the sternum four years before the mitral valve procedure.
      We could not select median-sternotomy as an approach due to stomach role beneath
      the sternum, nor left posterolateral thoracotomy because of the heavy left-side
      pleural adhesion. Cardio-pulmonary bypass cannulations were performed through the
      same incision, because severe atherosclerosis was found at the distal arteries of
      the abdominal aorta.

PMID- 9594503
TI  - [A case of submitral left ventricular pseudoaneurysm following mitral valve
      replacement for infective endocarditis].
AB  - A 25-year-old female presented with high fever and dyspnea. She was diagnosed as
      infective endocarditis, severe mitral regurgitation, grade II A-V block and acute
      left heart failure We performed emergency mitral valve replacement. At operation,
      mitral ring abscess was found which was extended to submitral left ventricular
      wall. The abscess was excised and the defect of mitral annulus was repaired with
      Xenomedica patch. Left ventriography at 30 days after the operation showed a
      submitral left ventricular pseudoaneurysm (size: 30 x 26 x 33 mm) without
      evidence of infection. Further examinations showed that the aneurysm extended to
      the annulus of tricuspid valve through interatrial septum. About 1 year after the
      operation, she had paroxysmal atrial fibrillation due to right atrial
      overloading. We decided to perform reoperation. At reoperation, the ostium of the
      aneurysm was closed with a Xenomedica patch after taking off the prosthetic
      valve. It was very difficult to close the ostium because we could not see the
      submitral ventricular wall directly. Although postoperative course was good, she
      had complete A-V block necessitating permanent pacemaker.

PMID- 9594504
TI  - [A case report of aortic valve replacement and ascending + hemi aortic arch
      replacement for congenital bicuspid aortic stenosis with poststenotic dilatation
      of ascending aorta].
AB  - The patient of 21-year-old female, who had undergone VSD closures at the age 5
      and had been pointed out to have aortic valve stenosis at that time, was admitted
      to our hospital with complaints of palpitation and easy fatigability. Pressure
      gradient of 140 mmHg between left ventricle and ascending aorta, and poststenotic
      dilatation of max 55 mm in diameter from ascending aorta to hemi aortic arch was
      recognized by cardiac catheterization and aortogram. For fear of aortic
      dissection in late phase caused by dilatation of ascending aorta left over, graft
      replacement from ascending aorta to hemi aortic arch was carried out
      simultaneously adding to aortic valve replacement (AVR). We are of the opinion
      that not only AVR but also simultaneous graft replacement should be performed
      actively on the case with dilatation of ascending aorta of over 55 mm in diameter
      in order to prevent aortic dissection.

PMID- 9594505
TI  - [Successful removal of a giant ball thrombus in the left atrium in an aged
      patient with unusual course].
AB  - A case of left atrial ball thrombus associated with severe mitral stenosis was
      reported. This male patient, aged 78, came in the chief complaint of leg and
      facial edema. An echocardiographic examination revealed the presence of mitral
      stenosis and floating giant ball thrombus in the atrium. He suffered from acute
      thromboembolism in his right leg six years ago and had been treated with
      anticoagulant since then. Despite this a floating giant ball thrombus was
      observed. Emergency operation including mitral valve replacement and thrombectomy
      was successfully performed. Thrombus formation in the left atrium is not uncommon
      but it is very rare to encounter in patients receiving anticoagulant therapy. To
      manage these patients well, meticulous attention must be paid during induction of
      anesthesia, intra-operative procedures, perioperative care, and operative
      position.

PMID- 9594506
TI  - [Lung cancer surgery in a patient with idiopathic thrombocytopenic purpura
      (ITP)].
AB  - A 59-year-old woman was hospitalized due to an abnormal chest X-ray film. Chest X
      ray examination revealed an irregular opacity in the right S6 area.
      Adenocarcinoma was diagnosed by bronchoscopic exfoliative cytology. Preoperative
      hematology tests showed a low platelet count and further investigation suggested
      the presence of idiopathic thrombocytopenic purpura. Preoperative high-dose
      immunoglobulin therapy (400 mg/kg/day for five days) and platelet transfusion
      allowed the operation to be performed successfully (resection of the inferior
      lobe of the right lung and removal of regional lymphnodes). High-dose
      immunoglobulin therapy is thought to be a very useful method with few adverse
      effects for the rapid increase of platelet count to prevent massive hemorrhage.

PMID- 9594507
TI  - [An infant with lobar emphysema requiring lobectomy after ventricular septal
      defect closure].
AB  - A 1-month-old male infant with respiratory distress was referred to our hospital
      for operation of the ventricular septal defect. A chest roentgenogram
      demonstrated pulmonary emphysema especially in the right upper and middle lobes.
      At 3 months, a perimembranous ventricular septal defect was closed. But the
      infant could not be weaned from the ventilator. On the 21st postoperative day, a
      right upper and middle bilobectomy was performed. Three days later, he was weaned
      from the ventilator and the postoperative course was uneventful. The pathologic
      diagnosis revealed no bronchial cartilagenous abnormality. Infantile lobar
      emphysema of the right upper lobe with congenital heart disease is rather rare.
      We emphasize the need for lobectomy simultaneous with, secondary to, cardiac
      surgery in these cases.

PMID- 9594508
TI  - [A case of complete mediastinal goiter located in the retrotracheal region:
      review on reported cases from 1986 to 1997 in Japan].
AB  - A 66-year-old man was admitted to our hospital as a result of an abnormal shadow
      which was observed on his chest X-ray. A chest CT scan and chest MRI revealed an
      upper mediastinal tumor. The tumor was located in the retrotracheal region and
      resected completely following a thoracotomy. Histological examination of the
      tumor revealed follicular adenoma of the thyroid gland. Complete mediastinal
      goiter is a relatively rare lesion, with only 59 cases (including our case) in
      Japan prior to 1997. Only two cases were reviewed, in which the tumors were
      located in the retrotracheal region, out of the 59 cases in Japan.

PMID- 9594509
TI  - [A case of mediastinal neurilemmoma originating from the intrathoracic vagal
      nerve].
AB  - A case of mediastinal neurilemmoma originating from the left intrathoracic vagal
      nerve was reported. A 42-year-old female was admitted to our hospital because of
      evaluation of an abnormal shadow on chest X-ray. Both CT and MRI showed that the
      tumor was located in middle mediastinum between the aortic arch and the left
      pulmonary artery, and the diagnosis was suspected to be neurilemmoma originating
      from the intrathoracic vagal nerve. Left standard thoracotomy was performed and
      the tumor was resected by amputating the vagal trunk. Pathological diagnosis was
      benign Antoni A and B type neurilemmoma. The postoperative course was uneventful
      with transient hoarseness. The patient is doing well with no relapse at 4 years 6
      months after the operation. Mediastinal neurilemmoma originating from the vagal
      nerve is rare and we discussed both the diagnosis and the surgical treatment for
      this disease.

PMID- 9594510
TI  - [The role of nitric oxide in hemorrhagic shock].
AB  - The continuous release of nitric oxide (NO) from the constitutive, endothelial
      isoform of nitric oxide synthase (e-NOS) serves mainly to keep the vasculature in
      a continuous state of active vasodilation. Although it has been suggested that NO
      production from e-NOS might also be affected by hemorrhagic shock (HS), this
      relationship is still controversial. Therefore, the roles of NO in the
      pathophysiology in hemorrhagic shock were reviewed. According to the previous
      reports, NO might play an important role in the pathophysioliogy of HS. In the
      early phase of HS, it may be possible that NO delivered from e-NOS serves a
      cytoprotective function in preventing shock-induced organ injury. This opinion
      suggests that endothelial NO production has a significant modulatory effect on
      vascular tone during hemorrhage, and that inhibition of NO production permits
      greater vasconstrictor influences leading to organ injury. NO production in the
      late phases of HS has an adverse effect on survival rate in the HS model.
      Moreover, the findings from an animal study of prolonged periods of HS suggest
      that excessive NO formation, including those produced from i-NOS, induces
      vascular hypoactivity and they have suggested that NOS inhibitors may improve the
      therapeutic outcome for patients suffering from HS. Therefore, it may be
      suggested that NO might play a biphasic role, cytoprotective during the early
      phase and cytotoxic late in HS.

PMID- 9594512
TI  - [Effect of diltiazem on jugular bulb oxygen saturation (SjO2)].
AB  - We investigated the effect of diltiazem on jugular bulb oxygen saturation (SjO2)
      in patients undergoing superficial temporal artery-middle cerebral artery
      anastomosis. In the presence of stable vital signs, diltiazem was administered by
      continuous infusion (2 micrograms.kg-1.min-1). There was no significant change in
      blood pressure, heart rate, SjO2 in response to diltiazem administration. The
      arterial plasma concentration of diltiazem reached 75 +/- 14.2 ng.ml-1 after 180
      min. The difference of areas under the curve between the arterial and jugular
      venous diltiazem concentrations from start of infusion to the end was
      significant. We conclude that this dose of diltiazem produced effective
      concentration and uptake in the brain tissue, but produced no significant effect
      on jugular bulb oxygen saturation (SjO2).

PMID- 9594511
TI  - [Positive end-expiratory pressure facilitates washout of nitrous oxide in
      patients with obstructive pulmonary disease].
AB  - This study was designed to investigate the relationship between nitrous oxide
      elimination and each value of pulmonary function tests: percent vital capacity,
      air way resistance and percent of forced expiratory pressure (FEV1.0%) in
      patients undergoing general anesthesia. Furthermore, the effect of positive end
      expiratory pressure (PEEP) on nitrous oxide elimination was studied. Thirty nine
      patients, anesthetized by oxygen, nitrous oxide and sevoflurane, were allocated
      randomly to one of two groups; one, with PEEP 10 cmH2O during nitrous oxide
      elimination and the other, without. After discontinuation of nitrous oxide, the
      concentration of nitrous oxide was measured at 15 sec intervals under controlled
      ventilation with 100% oxygen-sevoflurane. There was a significant correlation
      between nitrous oxide washout time and FEV1.0% (P < 0.05). Patients were further
      divided into two subgroups: FEV1.0% of over 70% (normal FEV) and that of less
      than 70% (low FEV). In the normal FEV group, the washout time was unaffected by
      PEEP. In the low FEV group, the washout times, with and without PEEP, were 7.07
      +/- 0.93 min and 9.13 +/- 2.32 min, respectively. The difference was significant
      (P < 0.05). These results suggest that patients with chronic obstructive lung
      disease are at risk of delay in nitrous oxide elimination. This delay was found
      to be preventable with PEEP.

PMID- 9594513
TI  - [The effects of flumazenil or bicuculline on the respiratory depression by
      morphine].
AB  - The effects of intravenous administration of flumazenil (n = 6) or bicuculline (n
      = 6) on the discharge of the phrenic nerve were studied following vagotomy in
      pentobarbital anesthetized mechanically ventilated rats. Morphine (0.4 mg.kg
      1.min-1) was administrated until the respiratory rate decreased to about a half
      of the baseline respiratory rate. In this state, we first administered flumazenil
      (0.25 mg.kg-1) or bicuculline (0.4 mg.kg-1), intravenously and then administered
      naloxone (0.02 mg) intravenously in the two groups. The increase of inspiratory
      time from 0.7 +/- 0.1 to 2.0 +/- 0.5 s by morphine recovered to 0.8 +/- 0.2 s by
      bicuculline and to 0.6 +/- 0.1 s by naloxone. The increase of inspiratory time
      from 0.7 +/- 0.1 to 1.7 +/- 0.3 s by morphine, and to 2.1 +/- 0.5 s by flumazenil
      recovered to 0.6 +/- 0.1 s by naloxone. Expiratory time did not change during
      each drug administration in the two groups. The decrease of respiratory rate from
      44 to 23 +/- 4 breaths.min-1 by morphine recovered to 37 +/- 5 breaths.min-1 by
      bicuculline and to 42 +/- 2 breaths.min-1 by naloxone. The decrease of
      respiratory rate from 45 +/- 3 to 22 +/- 6 breaths.min-1 by morphine, and to 18
      +/- 4 breaths.min-1 by flumazenil recovered to 46 +/- 3 breaths.min-1 by
      naloxone. Amplitude of integrated phrenic nerve discharge increased to 125 +/-
      42% by bicuculline and to 175 +/- 93% by naloxone compared to the baseline
      values. The decrease of amplitude to 54 +/- 18% by flumazenil recovered to 125 +/
      42% by naloxone. These results suggest that bicuculline not flumazenil
      antagonizes the respiratory depression of morphine by increasing the respiratory
      rate and respiratory movement.

PMID- 9594514
TI  - [Effects of fentanyl on hepatic circulation and hepatic oxygen metabolism in
      dogs].
AB  - Hepatic circulation, oxygen metabolism and energy charge level were assessed in
      12 mongrel dogs (10.6 +/- 0.9 kg) during cumulative administrations of fentanyl
      3, 10, and 30 micrograms.kg-1 i.v., under air-1% isoflurane anesthesia. Hepatic
      blood flow was measured with electromagnetic flowmeters. Hepatic oxygen delivery
      and consumption were calculated from measured hepatic blood flow and oxygen
      content in hepatic arterial, portal venous and hepatic venous blood. Hepatic
      energy charge was assessed by measuring the arterial ketone body ratio (AKBR),
      which is considered to be an indicator of mitochondrial energy charge level.
      Hepatic blood flow and oxygen metabolism did not change after administration of 3
      micrograms.kg-1 of fentanyl, but mean arterial blood pressure, cardiac output,
      hepatic arterial blood flow, portal venous blood flow and hepatic oxygen delivery
      were significantly suppressed by 30 micrograms.kg-1 of fentanyl. Hepatic oxygen
      consumption and AKBR were well maintained by spontaneous rises in hepatic oxygen
      uptake ratio. However, these results suggest that the significant decrease of
      hepatic oxygen delivery during administration of 30 micrograms.kg-1 of fentanyl
      could be exacerbated by combination with hypoxemia or hypoperfusion of the liver,
      and this might be followed by hepatic dysfunction.

PMID- 9594515
TI  - [Perioperative minimum acceptable hematocrit level in highly invasive head and
      neck surgery].
AB  - We examined the perioperative balance between oxygen delivery and oxygen
      consumption under hemodilution in 24 patients who underwent head and neck surgery
      of long duration and with massive blood loss. Intraoperative mixed venous oxygen
      saturation (SVO2), which decreased according to a decrease in hematocrit (Hct),
      was almost always kept above 60% when Hct was more than 20%. The longer the
      duration of surgery, the lower was SVO2 at the end of surgery. Postoperative SVO2
      correlated positively with SVO2 at the end of surgery, and negatively with the
      duration of surgery and blood loss, but did not correlate with Hct. In 9 cases,
      SVO2 at the recovery from anesthesia decreased to below 60%, because oxygen
      consumption increased remarkably with shivering. These results suggest that in
      highly invasive head and neck surgery, the intraoperative minimum acceptable Hct
      level is 20%. On the other hand, there is no general postoperative minimum
      acceptable Hct level, because postoperative oxygen demand and supply balance
      depends on the degree of surgical invasion and increase of VO2. SVO2 at the end
      of surgery is useful in predicting postoperative oxygen demand and supply
      balance.

PMID- 9594516
TI  - [The relationship between maintenance dose of vecuronium and the recovery time
      from the muscle relaxation].
AB  - We investigated the relationship between maintenance bolus dose of vecuronium
      bromide (Vb) and the recovery time measured by TOF Guard in patients anesthetized
      with isoflurane (1.2-2.0%)-N2O-O2 (GOI group, n = 19) and epidural anesthesia (2%
      mepivacaine) plus isoflurane (0.5%)-N2O-O2 (EPI group, n = 14). In both groups,
      anesthesia was induced with propofol 2 mg.kg-1 and Vb 0.1 mg.kg-1 and ventilation
      was controlled to keep end tidal CO2 between 35-40 mmHg. When the muscle
      relaxation recovered to 25% of train-of four ratio (TOFR), doses of Vb 0.06, 0.04
      or 0.02 mg.kg-1 were administered. Recovery time to TOFR 25% at each Vb dose (T
      0.06, T 0.04 and T 0.02 respectively) was observed. T 0.02, T 0.04 and T 0.06 in
      GOI group were 36.7 +/- 3.2, 50.7 +/- 4.3 and 60.7 +/- 5.02 min (mean +/- SE),
      respectively and those in EPI group were 42.6 +/- 2.53, 52.2 +/- 2.51 and 59.9 +/
      3.22 min, respectively. There were no significant differences in the recovery
      time between these two groups. In both groups, although the recovery time to TOFR
      25% was prolonged significantly in proportion to the increasing doses of Vb, the
      increase did not correlate with the dose of Vb. We suggest that frequent
      administration of Vb 0.02 mg.kg-1 decreases the total amount of Vb to keep TOFR
      within 25%.

PMID- 9594517
TI  - [Neurotoxicity of dibucaine on the isolated rabbit cervical vagus nerve].
AB  - The neurotoxicity of dibucaine was compared with that of commercially available
      local anesthetics in studies using rabbit desheathed cervical vagus nerve
      preparation. Dibucaine dose-dependently suppressed the evoked action potential of
      myelinated A beta nerve component and nonmyelinated C nerve component. The
      potential of A beta nerve component was more strongly suppressed, compared with
      that of C nerve component. At low concentrations of 0.0001-0.001%, the
      suppression was reversible and recovery with C nerve component was faster and
      more complete. At higher concentrations, the suppression was irreversible. The
      minimum concentrations of irreversible blockade were 0.003% for A beta nerve
      component and 0.03% for C nerve component. Electron microscopically, marked
      damages in the myelin layer and intraaxonal structure were observed in nerves
      treated with 0.03% dibucaine. When the neurotoxic effect of dibucaine was
      compared, in terms of safety margins (minimum concentration of irreversible
      blockade/clinically used concentrations), with those of commercially available
      local anesthetics, the rank order was dibucaine, tetracaine and bupivacaine;
      dibucaine showing the lowest safety margin.

PMID- 9594518
TI  - [Clinical study of AJ-007 (bupivacaine) in spinal anesthesia--investigation of
      clinical dosage of isobaric and hyperbaric formulations].
AB  - Spinal anesthesia with two types of 0.5% bupivacaine hydrochloride solution,
      isobaric AJ-007 I and hyperbalic AJ-007 H, was studied clinically in 106 surgical
      patients with collaboration of 7 university hospitals. The following results were
      obtained. 1) Successful analgesia with motor block on abdominal wall and legs
      could be induced by dosages of 2.0 ml, 3.0 ml and 4.0 ml of either of the two
      solutions. 2) With isobaric solutions, the duration of the block was prolonged
      dose dependently. Anesthetic levels tended to increase and onset times of the
      block tended to decrease, with increasing dosage. 3) Hyperbalic solutions tended
      to produce higher levels of the block more rapidly. However, the duration of the
      block seemed to be shorter than that achieved by isobaric solutions. 4) The
      incidence of hypotension and bradycardia was similar to that observed in ordinary
      clinical spinal anesthesia. In one young male, a high level (C 2) of anesthesia
      was achieved after administration of 4.0 ml of hyperbaric solution. This patient
      was managed uneventfully under general anesthesia during the surgery. These
      results indicate that these two solutions of 0.5% bupivacaine are useful for
      spinal anesthesia.

PMID- 9594519
TI  - [Effect of the continuous epidural buprenorphine injection in patients after
      lower extremity arthroplasty].
AB  - We studied the analgesic effects of continuous epidural injection of
      buprenorphine in patients after lower extremity arthroplasty. In these patients
      anesthesia was maintained only with lumbar epidural anesthesia with 2%
      mepivacaine. We employed a balloon type continuous infuser (DIB Catheter, 40
      ml.day-1) for postoperative analgesia for twenty-four hours. The patients were
      classified into three groups according to the method of buprenorphine injection
      and the content of DIB Catheter. First group (group A ; N = 37) received
      buprenorphine (0.2 mg) with 0.25% bupivacaine (40 ml) for twenty-four hours. Next
      group (group B ; N = 27) received bolus injection of buprenorphine (0.2 mg) for
      the first additional epidural injection of local anesthetic and received
      continuous injection of buprenorphine (0.2 mg) with 0.25% bupivacaine (40 ml) for
      twenty-four hours. The last group (Group C ; N = 40) also received bolus
      injection of buprenorphine as in group B, but received continuous buprenorphine
      infusion with normal saline instead of local anesthetics. The analgesic effect
      was determined by the postoperative usage of other analgesics (NSAID or
      pentazocine) by request of patients. In twenty-four hours, the numbers of
      patients who did not request other analgesics were 6 (Group A. 16%), 9 (Group B.
      33%) and 19 (Group C. 48%), respectively. In Group A, 18 patients requested
      analgesics, but only 8 patients requested in Group C. It was effective for the
      postoperative analgesia to use the continuous epidural injection with DIB
      Catheter for patients after lower extremity arthroplasty. It was necessary to
      give a bolus injection of buprenorphine before the end of surgery for sufficient
      analgesia, but it was not necessary to add local anesthetics in the content of
      DIB Catheter.

PMID- 9594520
TI  - [Sudden ventricular tachyarrhythmia immediately following hepatectomy in a
      patient with hypomagnesemia].
AB  - A 57-year-old male without pre- or intraoperative arrhythmia developed
      ventricular tachyarrhythmia immediately following hepatectomy. Postoperative
      examination of plasma electrolytes revealed severe hypomagnesemia (0.16 mmol.l
      1). The arrhythmia may have been caused by hypomagnesemia and an imbalance
      between supply and demand of oxygen in the myocardium, due to hypovolemia and
      severe anemia from massive hemorrhage. We recommend that measurement of plasma
      magnesium concentration be included in all perioperative laboratory examinations.

PMID- 9594521
TI  - [Postoperative respiratory disturbance after anterior cervical fusion].
AB  - We examined 171 patients who had undergone anterior cervical fusion to determine
      the frequency and the causes of postoperative respiratory disturbance (PRD).
      Postoperative tracheal intubation was necessary in 11 patients (6.4%), but only 4
      of them (2.3%) required reintubation due to PRD caused by surgical procedures.
      PRD has been reported to occur at various frequencies in previous studies, partly
      due to unsettled criteria of PRD, miscellaneous primary diseases, and
      heterogeneous surgical procedures. As C 3 was fused in the 4 patients with PRD,
      requiring reintubation, upper airway obstruction due to serious swelling of the
      soft tissue surrounding C 3 might be the factor leading to postoperative
      reintubation. One of the PRD patients who suffered from postoperative unilateral
      phrenic nerve palsy required controlled ventilation.

PMID- 9594522
TI  - [The "walking" epidural catheter: one cause of failed epidural anesthesia].
AB  - We report a "walking" catheter resulted in failed epidural anesthesia. An 85-year
      old woman was scheduled for insertion of a nail in the left humerus. At 10 a.m.
      on the day of surgery, a Tuohy needle was inserted into the epidural space
      between the C6 and C7 vertebrae, and then we inserted an epidural catheter for 5
      cm. Epidurography revealed that the catheter was inserted between C5 and C6, and
      the tip of the catheter was positioned windingly at C4. The contrast medium was
      found spread bilaterally from the C2 level to the Th2 level. The patient entered
      the operating room at 3 p.m. We infused 10 milliliters of 1% mepivacaine through
      the epidural catheter. Hypesthesia was obtained on the right side of her neck,
      from the C2 to the C5 level, after 10 minutes. Epidurography after surgery showed
      that the coiled catheter was placed straight into the right side of the epidural
      space; contrast medium infused through the catheter was found spread only to the
      right side from the C2 to the C4 level.

PMID- 9594523
TI  - [Transient global amnesia after general anesthesia].
AB  - A 61 year old male patient with left mandibular cyst, received marsupialization
      of the left mandible under general anesthesia. Four hours after the end of
      anesthesia, his memory for the past 4 months and short term memory plastisity
      were impaired. No neurological abnormalies were found at that time. On the 2nd
      postoperative day, he recovered his lost memory for the past 4 months. The memory
      of events between 6 hours before operation and next morning, however, remained
      lost. It is suggested that the memory disorder is the TGA due to various causes
      including transient hypertension, operative stress, postoperative pain and
      diazepam.

PMID- 9594524
TI  - [A case of pheochromocytoma incorrectly diagnosed before and during surgery].
AB  - In a patient with an adrenal tumor, although norepinephrine levels in the blood
      and urine were abnormally high, findings in CT and 131 I-MIBG scintigraphy denied
      pheochromocytoma. The preoperative diagnosis was metastatic adrenal tumor. The
      surgical manipulation of the tumor increased the blood pressure from 110/60 to
      210/110 mmHg. However, intraoperative microscopic examination in frozen section
      excluded again possibility of pheochromocytoma. Later, findings in the permanent
      specimen confirmed that the tumor was pheochromocytoma. The problem of this case
      was that each specialist made judgment only on the subject of his own interest
      without considering of the patient's status as a whole. Anesthesiologist should
      have the ability to make preoperative assessment of a patient by using all
      available information with his unbiased mind.

PMID- 9594525
TI  - [A case of the CHARGE association with failed tracheal intubation].
AB  - We experienced a patient with the CHARGE association whose trachea could not be
      intubated in spite of attempts of laryngoscopy by four experienced
      anesthesiologists. Laryngeal fiberscope and neck X-ray examination carried out
      after the surgery, revealed the obvious enlargement of adenoid and tonsils,
      pressing the epiglottis to the posterior wall of the larynx. Although it is
      unknown whether enlargement of adenoid and tonsils are specific to the CHARGE
      association or not, patients with the CHARGE association are considered to have
      difficult airway. Preanesthetic evaluation of airway is indispensable for
      anesthesia in the patients with the CHARGE association.

PMID- 9594526
TI  - [Circulatory collapse during laparoscopic cholecystectomy].
AB  - A 52 year-old female without any cardiac disease underwent laparoscopic
      cholecystectomy. Anesthesia was induced with thiamylal and maintained with
      nitrous oxide and isoflurane. Epidural anesthesia was also used during surgery.
      When the intraabdominal insufflation was performed in reverse-trendelenburg
      position 15 minutes after the start of incision, the heart rate suddenly
      decreased from 75 to 49 bmp with a fall in blood pressure. Her hemodynamic state
      recovered immediately after the release of intraabdominal pressure and the
      administration of ephedrine with a rapid infusion of Hespander. The circulatory
      collapse did not occur when the second insufflation was tried carefully. The
      circulatory collapse was probably due to the vagal reflex. The decrease in
      cardiac preload during the reverse trendelenburg position and the epidural
      administration of local anesthetics may have caused or worsened the circulatory
      collapse. In anesthetic managements of laparoscopic cholecystectomy using general
      anesthesia with epidural anesthesia, prophylactic hydrogenation and prevention of
      parasympathetic domination are important to minimize the vagal reflex.

PMID- 9594527
TI  - [Anesthetic management of abdominal gunshot wound--a report of three cases].
AB  - This is a case report of anesthetic management of abdominal gunshot wound. Two
      patients had upper abdominal wound involving the liver and the inferior vena
      cava. They died of uncontrolled bleeding. Third patient had lower abdominal
      injury involving the ascending colon and small intestine. The patient survived
      the injury and showed good recovery. In a case of the abdominal gunshot injury,
      prompt diagnosis and laparotomy are mandatory. Multiple intravenous routes are
      necessary in the upper part of the body for massive infusion and transfusion.
      Unusual hemostasis methods such as atrio-caval shunt or abdominal clamping of the
      aorta must be considered in case of injury in the inferior vena cava.

PMID- 9594528
TI  - [Classification of cardiomyopathies according to the WHO/ISFC Task Force--more
      questions than answers?].
AB  - The most recent WHO/ISFC classification of cardiomyopathies (1995) describes as
      cardiomyopathies all heart muscle diseases, which demonstrate a disturbance of
      cardiac function. It distinguishes primarily according to hemodynamic criteria
      the following 5 forms: 1. dilated (DCM), 2. hypertrophic (HCM), 3. restrictive
      (RCM) from 4. arrhythmogenic right ventricular (ARVCM) and assembles in 5. non
      classified cardiomyopathies (NKCM) the non-classifiable forms. When compared to
      the 18-year-old former classification several points have been altered: 1. ARVCM
      has been introduced as a new entity. 2. The new term ischemic cardiomyopathy has
      been reserved for the remodeling process of the non-infarcted myocardium and does
      not mean hemodynamic alterations of an infarcted area (aneurysm), of stunned or
      hibernating myocardium. Hypertensive cardiomyopathy corresponds to left
      ventricular hypertrophy in hypertensive patients, valvular cardiomyopathy
      identifies cardiomegaly, which cannot sufficiently be explained by the valvular
      dysfunction (stenoses or insufficiency) alone. For the first time the term
      inflammatory cardiomyopathy has been used and defined as acute or chronic
      myocarditis associated with cardiac dysfunction, for which etiological and
      pathogenetic factors, e.g. viral or microbial infection or autoimmune processes
      have been made responsible. Two ISFC task forces have just recently clarified in
      consensus conferences the immunohistopathological criteria for chronic
      myocarditis or dilated cardiomyopathy with inflammation (DCMi: > 14 lymphocytes
      or macrophages/mm3) and set standards for molecular and virological diagnoses in
      endomyocardial biopsies.

PMID- 9594529
TI  - [Genetics of dilated cardiomyopathy].
AB  - Dilated cardiomyopathy (DCM) is a heart muscle disorder characterized by cardiac
      dilatation and impaired systolic function. In an increasing number of all DCM
      cases a specific etiology can be identified and in the remaining patients DCM is
      termed idiopathic. There is a wide variation of the clinical presentation in DCM.
      The majority of patients manifests classical disease, i.e. heart failure due to
      left (and right) ventricular systolic dysfunction. However, some cases may come
      to clinical attention because of supraventricular arrhythmias such as sinus node
      dysfunction, AV-block or atrial fibrillation. Although a multitude of etiologies
      may be responsible for DCM (e.g. viral, immunological, toxic), the disease is
      inherited as a single gene disorder in at least 20 to 35% of cases. Most genetic
      forms of DCM are caused by autosomal dominant gene defects. Six dominant disease
      loci on chromosomes 1p1-q1, 1q32, 3p22-p25, 6q23, 9q13 und 10q21-q23 have been
      identified but the corresponding disease genes are not yet known. X-linked DCM
      without skeletal muscle disease is a rare variety of adult DCM which can be
      caused by specific mutations in the dystrophin gene on chromosome Xp21.

PMID- 9594530
TI  - [Enteroviral myocarditis and dilated cardiomyopathy].
AB  - In situ hybridization and PCR studies have demonstrated that enteroviruses of the
      human picornavividae, and in particular coxsackieviruses of group B (CVB), are
      detectable in endomyocardial biopsies of patients with acute and chronic
      myocarditis, indicating the possibility of enterovirus persistence in the human
      heart. As well, such infections are observed in patients with end-stage dilated
      cardiomyopathy, suggesting an etiologic link between myocarditis and dilated
      cardiomyopathy. The molecular diagnosis of persistent heart muscle infection
      allows to differentiate myocarditis and dilated cardiomyopathy, sustained by
      virus persistence, from postviral immune-mediated cardiac disease. Apart from
      providing an etiologic diagnosis, there are therapeutic implications from in situ
      demonstration of myocardial enterovirus infection. As to whether antiviral
      therapy with interferon is capable of providing protection against enterovirus
      myocarditis must be determined by controlled prospective clinical studies.
      Immunosuppressive therapy of myocarditis appears to be justified only after
      exclusion of persistent heart muscle infection. Experimental studies indicate
      that altered viral replication strategies, the incompetence of effector mediators
      of local immunity to eliminate persistently infected myocardial cells as well as
      infection of cellular constituents of the immune system itself, are major
      pathogenic determinants for development and maintenance of chronic myocarditis
      and cardiomyopathy.

PMID- 9594531
TI  - [Cardiotropic DNA viruses and bacteria in the pathogenesis of dilated
      cardiomyopathy with or without inflammation].
AB  - In the report of the 1995 WHO/ISFC task force on the definition and
      classification of cardiomyopathies a new entity within the dilated
      cardiomyopathies was introduced as "inflammatory cardiomyopathy". It is defined
      as myocarditis associated with cardiac dysfunction. Idiopathic, autoimmune and
      infectious forms of inflammatory cardiomyopathy are now recognized through this
      definition. Dilated cardiomyopathy with inflammation (DCMi, chronic myocarditis)
      was also defined by a recent ISFC task force as > 14 lymphocytes/macrophages/mm3.
      Enteroviruses, adenoviruses and cytomegaloviruses are considered as main
      etiopathogenetic factors in the pathogenesis of inflammatory heart disease and
      have been demonstrated as important trigger for inflammatory cardiac disease.
      They may also cause dilated cardiomyopathy by viral persistence or secondary
      immunopathogenesis due to antigenic or molecular mimicry. For the detection of
      viral persistence the investigation of endomyocardial biopsies in patients with
      cardiomyopathy by the use of polymerase chain reaction and southern blot analysis
      is an important step for the standardization of diagnostic criteria on virally
      induced inflammatory cardiomyopathy. Present studies indicate an incidence of
      cytomegalovirus-DNA in patients with inflammatory cardiomyopathy in 10%,
      adenoviral-DNA in 17% and borreliosis only in rare cases (< 1%). In dilated
      cardiomyopathy without inflammation the respective incidences were for
      cytomegalovirus 12%, 15% for adenovirus and only 0.5% of cases for borreliosis.
      In addition the results of immunohistochemical analysis and molecular biological
      investigations of endomyocardial biopsies may have implications for future
      therapeutic studies. Depending on the etiology of the disease, immunosuppression
      may have benefit for patients with virus-negative cardiomyopathy with
      inflammation in contrast to patients with cytomegalo-, adenovirus-DNA or
      enteroviral persistence, in whom immunomodulation with hyperimmunoglobulins or
      immunoglobulins may be a feasible therapeutic option. Patients with a positive
      PCR for Borrelia burgdorferi should be treated with 3rd generation
      cephalosporines and/or sublactam.

PMID- 9594532
TI  - [Pathogenesis of inflammatory cardiomyopathies].
AB  - The development of dilated cardiomyopathy from chronic myocarditis is caused by
      the persistence of enteroviral infections and chronic myocardial inflammation.
      New molecularbiological and immunohistochemical techniques improve diagnosis and
      allow predictions of the development of the disease. This facilitates the
      decision for a specific immunomodulatory therapy.

PMID- 9594533
TI  - [Clinical picture and differential diagnosis of cardiomyopathy and myocarditis].
AB  - The main feature of idiopathic dilated cardiomyopathy is the dilation and
      impaired contractility of the left ventricle or both ventricles. The clinical
      picture with forward and backward failure is based on the pump impairment of the
      left ventricle. However, the clinical presentation of patients with dilated
      cardiomyopathy is indistinguishable from any other secondary form of heart
      failure. The symptoms of myocarditis are also often determined by the degree of
      left ventricular dysfunction and--apart from perimyocarditis-associated
      precordial discomfort--therefore also often indistinguishable from dilated
      cardiomyopathy. The differentiation of dilated cardiomyopathy from other
      myocardial diseases by noninvasive methods is insufficient. Without invasive
      tests about 1/3 of the patients will be diagnosed incorrectly. Therefore,
      invasive diagnostics including coronary angiography are necessary to
      differentiate dilated cardiomyopathy from other diseases, especially coronary
      artery disease. Standard laboratory findings and cytokine serum concentrations
      (e.g. TNF-alpha) are not suitable to differentiate dilated cardiomyopathy and
      myocarditis and endomyocardial biopsy is indicated. Endomyocardial biopsies have
      to undergo evaluation by standard histology and immunohistology, and should be
      tested for the persistence of infectious agents. According to cardiac
      catheterization and evaluation of the endomyocardial biopsy idiopathic left
      ventricular dysfunction can be further stratified using the criterion of a
      myocardial virus persistence and the presence/absence of inflammatory
      infiltrates. Idiopathic dilated cardiomyopathy (approximately 70 to 75%), virus
      associated dilated cardiomyopathy (approximately 20 to 25%), myocarditis
      (approximately 7%) and autoimmune myocarditis (approximately 3%) are the 4
      possible resulting forms of idiopathic left ventricular dysfunction. Beside
      conventional medical therapy there are new therapeutic concepts e.g. using
      interferon for enterovirus-positive patients and immunosuppression for
      autoimmune, virus-negative patients with a cellular infiltrate.

PMID- 9594534
TI  - [Therapy of dilated cardiomyopathies with and without inflammation].
AB  - Diagnosis of inflammatory dilated cardiomyopathy relies on the histological and
      immunohistological examination of endomyocardial biopsies. Only with the
      demonstration of the etiological agents in the myocardium specific therapy can be
      attempted. Whereas the spontaneous course of endemic myocarditis with little
      hemodynamic impairment is fair, the prognosis of symptomatic myocarditis and
      dilated cardiomyopathy is poor, with complete restitution in 35% and a 10-year
      survival rate of 30%. Restriction of physical activity is a validated form of
      therapy with normalization of the heart size in 40 to 60%. Symptomatic medical
      therapy consists of digitalis, diuretics, ACE-inhibitors and vasodilators and
      betablocker therapy, where a reduction of mortality was demonstrated in clinical
      (sub)studies up to 60%. Specific forms of therapy in inflammatory cardiomyopathy
      rely on the demonstration or lack of viral persistence or signs of autoreactivity
      in the myocardial tissue. Immunosuppressive therapy in autoimmune forms improved
      cardiac function in up to 60% of the patients in controlled trials, when compared
      to controls (40%). The double-blind randomized myocarditis treatment trial, which
      unfortunately did not distinguish viral from autoimmune myocarditis could not
      demonstrate such a benefit, however. Depending on the etiology of the disease,
      immunomodulation with immunoglobulins or interferon or antiviral therapy with
      hyperimmunoglobulins are presently tested in clinical treatment trials (ESETCID)
      in patients with enterovirus-positive or cytomegalovirus-positive and adenovirus
      positive chronic myocarditis. Specific therapies are aimed to avoid the
      progression of the disease which may ultimately lead to heart failure with a
      cardiac assist device or heart transplantation as ultimate therapeutic option.

PMID- 9594535
TI  - [Genetic causes of hypertrophic cardiomyopathy].
AB  - Hypertrophic cardiomyopathy is a dominantly inherited disease of the heart.
      Heterogeneous sets of mutations responsible for this condition have been
      identified in seven genes coding for proteins involved in the contraction
      mechanism or in the control of contraction of the myocardium. Known mutations
      imply structural and functional changes in the following proteins: in ventricle
      specific beta-myosin heavy chain, in essential and regulatory myosin light
      chains, in troponin subunits T and I, in alpha-tropomyosin and in myosin binding
      protein-C. The gene of one additional genomic HCM-locus is not known. Since two
      thirds or more of all cases can be traced to one of the respective genes, HCM has
      been classified as a disease of the cardiac sarcomere. Heterogeneity does not
      only exist between genes, but also within genes. At least 84 different mutations
      have been identified to date. More than half of them have been detected in the
      beta-myosin heavy chain gene. Thus, mutations in this gene account for most of
      the cases of HCM. The extent of data about causes is in contrast to the lack of
      definite knowledge about pathogenic mechanisms. Since the disorder is in many
      cases mild with symptoms developing frequently not before the end of the second
      decade, myocardial dysfunctions can presumably not directly be traced to altered
      contractility, but rather to effects which accumulate with a long asymptomatic
      lag period and which gradually lead to hypertrophy, conduction problems and
      ultimately to cardiac failure. The disease may be considered as an indirect and
      secondary response to a mildly distorted contraction process. The rapid progress
      in the analysis of causes suggests that the study of genes will assume a role in
      the context of the clinical management of HCM, in particular regarding diagnosis,
      prognosis, counselling of patients and families and--possibly--therapy.

PMID- 9594536
TI  - [Clinical picture and therapy of hypertrophic cardiomyopathy].
AB  - Hypertrophic cardiomyopathy is defined as a primary, sometimes familial and
      genetically fixed myocardial hypertrophy. In the obstructive form of the disease
      (HOCM) a dynamic outflow tract obstruction of the left, occasionally also the
      right ventricle can be found. HOCM is the most frequent cause of stress-induced
      syncope or sudden cardiac death in younger patients. An individual estimation of
      prognosis is difficult although several risk factors have been identified. In
      addition to standard therapy of symptomatic patients (medical treatment with
      betablockers and calcium-antagonists of verapamil-type as well as surgical
      myotomy/myectomy) DDD-pacemaker implantation and percutaneous transluminal septal
      myocardial ablation (PTSMA) by alcohol-induced septal branch occlusion have been
      introduced. After PTSMA significant outflow tract gradient reduction can be
      achieved in > 90% of patients. Due to remodeling after circumscribed myocardial
      necrosis further gradient reduction has been observed during follow-up.
      Optimization of ablated septal area by echocardiographic monitoring resulted in
      reduction of the most important complication (trifascicular block with need of
      permanent pacemaker implantation) and improvement of acute and follow-up results.
      Long-term follow-up and comparison with established treatment options are
      necessary to evaluate the definitive importance of the promising new treatment.

PMID- 9594537
TI  - [Arrhythmogenic right ventricular cardiomyopathy. Etiology, diagnosis and
      therapy].
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by
      regional atrophy of right ventricular myocardium and subsequent replacement by
      fatty and fibrous tissue. The disease manifests in young adulthood with a
      predominance of males. Hallmarks of ARVC are ventricular tachyarrhythmias of left
      bundle branch block pattern which frequently occur during exercise. However,
      sudden death may also be the first manifestation of the disease. Characteristic
      findings are repolarization abnormalities and QRS prolongation in the right
      precordial leads of the surface ECG and regional abnormalities of right
      ventricular structure and wall motion. Left ventricular involvement may occur in
      later stages of the disease but rarely leads to progressive biventricular heart
      failure. Therapeutic efforts are mainly directed to the treatment of ventricular
      tachyarrhythmias and the prevention of sudden death. A tailored treatment
      strategy including antiarrhythmic drug therapy, catheter ablation and
      implantation of cardioverter-defibrillators may be used to improve the long-term
      prognosis of patients with ARVC.

PMID- 9594538
TI  - [Extracellular matrix in cornea].

PMID- 9594539
TI  - [Changes in extracellular matrix components after excimer laser photoablation in
      rat cornea].
AB  - To understand the response of rat corneal wound healing after excimer laser
      photoablation, we observed the chronological changes in the localization of type
      I collagen, fibronectin, laminin, and type IV collagen after photoablation of the
      rat cornea. With immunofluoresence techniques, no obvious changes in the
      localization of type I collagen could be observed in the area of the wound.
      However, the localization of fibronectin, laminin, and type IV collagen was
      dramatically changed. One day after ablation, the fluorescein intensity of
      fibronectin increased at the denuded surface. After that, fibronectin, laminin,
      and type IV collagen were dramatically increased, especially in the shallow layer
      of the stroma, until about 7 days after ablation. In hematoxylin-eosin staining,
      keratocytes disappeared transiently from the area of the wound 1 day after
      ablation and then activated keratocytes migrated to the area. These results
      suggested that activated keratocytes might actively synthesize the extracellular
      matrix components. Therefore, sustained responses of keratocytes may be induced
      by excimer laser photoablation.

PMID- 9594540
TI  - [Experimental glaucoma model in the rat with laser trabecular photocoagulation
      after intracameral injection of India ink].
AB  - We tried to create an experimental glaucoma which is simple and highly
      reproducible in rodents. India ink was injected into the anterior chamber with a
      30-gauge needle. The carbon particles were trapped in the chamber angle and
      formed a black band along the corneal limbus one week later. This area was then
      photocoagulated anteroposteriorly with an argon laser. Photocoagulation was
      repeated until the intraocular pressure was elevated to 25 mmHg or more by
      pneumotonometry performed at a one-week interval. The above procedure was applied
      to one eye of 7 rats with the fellow eye serving as control. Chronic elevation of
      intraocular pressure was obtained in all the 7 treated eyes. The eyes were then
      enucleated and examined by light microscopy. Carbon particles were phagocytosed
      by macrophages in the intertrabecular spaces. Peripheral anterior synechias were
      also present. The optic nerve-head showed remarkable decrease in nerve fibers and
      cavernous degeneration suggestive of glaucomatous optic nerve damage. This
      experimental model promises to be of value in further studies of glaucomatous
      optic nerve damage.

PMID- 9594541
TI  - [Biocompatibility of polyvinylalcohol gel as a vitreous substitute].
AB  - Polyvinylacohol (PVA) gel cross linked by gamma irradiation was assessed as a
      possible vitreous substitute. In our previous, reports, elevation of intraocular
      pressure and inflammatory changes in the vitreous cavity after operation were
      observed in some of the experimental animals. Four types of PVA gel (sol) were
      produced by a newly refined method. We improved the gel systhesis process to
      remove the monomer and contamination. Colored rabbits were used for this
      experiment. Vitreous replacement was performed after vitrectomy. This was
      followed clinically by ophthalmoscopy, tonometry, fundus photography,
      electroretinogram, chemotaxis, and laser-flare-cell-metering. Histopathological
      examination by light microscopy was performed after 3 months. PVA gel has good
      biocompatibility in the vitreous cavity, and gel with a network similar to that
      of the vitreous body showed the best biocompatibility. Although it is necessary
      to investigate the biocompatibility over the long term and to evaluate the
      tamponade effect, PVA gel will be a bood candidate for a vitreous substitute.

PMID- 9594542
TI  - [Repetitive instillations of cyclosporin A eyedrop induce pupillary constriction
      and anterior chamber inflammation-like reactions in rabbits].
AB  - We attempted to clarify the mechanism of atropine-resistant miosis caused by
      repetitive instillations of cyclosporin A (CyA) eye drop in rabbits by
      investigating the possibility that the miosis may be attributable to CyA-induced
      contraction of the iris sphincter muscle, and that it may be resulting from
      inflammatory or inflammation-like reactions caused by CyA in living rabbit eyes.
      CyA did not induce contraction of the isolated iris sphincter muscle. Eight Dutch
      rabbits were given repetitive instillations of 0.1% CyA eye drops, and 7 rabbits
      (87.5%) exhibited miosis, accompanied by conjunctival and pericorneal hyperemia,
      and increased anterior flare 6 to 12 hours after the instillations. Fibrinoid
      formation in the anterior chamber was observed in 4 rabbits (50.0%). All of these
      findings were inhibited by treatment with anti-inflammation drugs, especially by
      indomethacin. After repetitive applications of 0.1% CyA eye drops, breakdown of
      the blood-aqueous barrier was observed in the ipsilateral iris vessels and
      cilliary epithelium. Increase in the aqueous protein concentration was noted, but
      there were no changes in the cell number. Repetitive instillations of the vehicle
      and single instillation of 0.1% CyA did not induce these inflammation-like
      findings. These results indicate that the miosis is a secondary effect resulting
      from ocular inflammation-like reactions and breakdown of the blood-aqueous
      barrier caused by excessive application of CyA.

PMID- 9594543
TI  - [Electrophysiological specification of trabecular meshwork by dielectric
      dispersion method].
AB  - In an attempt to observe the dielectric behavior of the trabecular meshwork and
      to estimate its pumping of aqueous humor quantitatively, we measured tissue
      impedance of the anterior portion of 22 enucleated eyeballs from 11 rabbits non
      invasively with a minute coaxial surface probe. Serial measurements of five
      points near the limbus revealed a significant decrease of the peak value (p <
      0.05, paired t-test) on loss tangent function at a point 0.5 mm from the limbus
      towards the sclera. We considered that the decrease in the peak value at the
      point was due to broadening of the dielectric dispersion reflecting the
      microstructure of trabecular meshwork beneath the point. After removing the
      corneal epithelium, the limbal epithelium, and the conjunctiva, we also observed
      a decrease in the peak value at the same point, which reinforced our assumption
      that we can identify the trabecular meshwork electrophysiologically by means of
      dielectric dispersion.

PMID- 9594544
TI  - [Inhibitory effects of matrix metalloproteinase inhibitor on corneal
      neovascularization].
AB  - We evaluated the inhibitory effects of matrix metalloproteinase inhibitor (MMPI)
      on corneal neovascularization in vivo. MMPI drops in the right eye and MMPI basic
      drops in the left eye were administrated six times per day after wearing a large
      polymethylmethacrylate-hard contact lens (PMMA-HCL) and intralamellar
      transplantation of a basic fibroblast growth factor (basic-FGF) containing
      polymer disk. We observed the status of corneal neovascularization with a slit
      lamp biomicroscopically after two weeks. Corneal buttons were also investigated
      histologically with light and electron microscopes. The findings of both
      investigations showed MMPI eye drops tended to inhibit the corneal
      neovascularization.

PMID- 9594545
TI  - [Four newborns with retinopathy similar to oxygen-induced retinopathy].
AB  - We report 4 fullterm newborns who developed retinopathy similar to oxygen-induced
      retinopathy after high concentration oxygen therapy for pneumothorax and
      emphysema. Two of them had a severe condition, showing marked dilatation,
      winding, and abnormal branching of the retinal vessels, especially veins, and
      retinal trubidity. Comparison between the 4 patients and controls without such
      retinopathy suggested that factors such as the oxygen concentration, the duration
      of oxygen therapy, the gradual reduction method, and the high level and changes
      in PaO2 were involved in the development of the retinopathy. Even in fullterm
      infants, treatment should be performed with consideration of the possible
      occurrence of changes in the eye fundus.

PMID- 9594546
TI  - [A case of syringomatous carcinoma derived from the lid].
AB  - A 73-year-old male presented with a slowly growing tumor in the right lower
      eyelid of one year's duration. The condition had been diagnosed elsewhere as
      poorly differentiated squamous cell carcinoma by biopsy. The residual tumor
      progressed rapidly and metastatized to the ipsilateral preauricular lymph nodes.
      We performed orbital evisceration and radical neck resection. Microscopically,
      the tumor showed small epithelial nests, cords, and ductal structure buried in
      abundant collagenous stroma. Besides focal squamous differentiation with
      keratinization in the surface area, the tumor showed, as cardinal features,
      ductal differentiation possessing comma-like extensions identical to syringoma.
      Cellular atypia, invasive growth pattern, and remarkable perineural invasion were
      suggestive of malignancy. These features led to the diagnosis of syringomatous
      carcinoma. Immunohistologically, the tumor showed positive staining for
      cytokeratine and epithelial membrane antigen (EMA). It was mostly negative for S
      100 and carcinoembryonic antigen (CEA).

PMID- 9594547
TI  - [Micro-organism and self-response].

PMID- 9594548
TI  - [Usefulness of magnetite as an MRI contrasting agent in an experimental cerebral
      ischemic model evaluation of injecting time point].
AB  - The superacute stage of focal ischemia can be visualized using T2-weighted MRI
      following the injection of superparamagnetic iron oxide particles (magnetite). In
      this study we evaluated the optimal time point, i.e. the time producing the
      strongest signal, for the injection of magnetite using T2-weighted MRI following
      left parmanent middle cerebral artery occlusion (lt.-PMCAO). Male Sprague-Dawley
      rats were anesthetized and the left middle cerebral artery (lt.-MCA) was
      permanently occluded. Magnetite was then injected into the femoral vein after 20
      to 30 min of lt.-PMCAO. T2-weighted MR images were taken immediately, and 15 and
      30 min after magnetite injection. A high signal area at the region of the lt.-MCA
      was clearly seen on the T2-weighted MRI immediately after magnetite injection.
      However, it became less clear after 15 min, and by 30 min could not be
      distinguished. These results suggest that magnetite should be injected
      immediately prior to T2-weighted MR imaging during the superacute stage of focal
      ischemia.

PMID- 9594549
TI  - [Cerebral blood flow of patients with age-associated memory impairment and the
      early stage of Alzheimer's disease. A study by SPECT using the ARG method].
AB  - In order to further understand the pathology of Alzheimer's disease (AD), we have
      utilized image analysis in diagnosing the early stages of AD in patients with
      cognitive disorders. CT and MRI, however, have not been feasible since only
      atrophy is seen and it is difficult to differentiate the changes in AD from age
      associated changes. In this study we tried to determine whether regional cerebral
      blood flow (rCBF) measurements using single photon emission CT (SPECT) are
      feasible for the early diagnosis of AD. Regional CBF (rCBF) was measured using
      SPECT in three subject groups: Age-associated memory impairment (AAMI. n = 9),
      mild AD (n = 16), and normal aged patients (mean age = 68.3; n = 20). The
      subjects were then observed for three years. The region of interest (ROI) for the
      medial temporal lobe was set at OM-30 degrees to cover the maximum area of the
      hippocampus. The absolute values of rCBF in the frontal, temporal, and parietal
      lobes and the cerebellum were significantly lower in the mild AD subjects than in
      the normal aged subjects. A significant decrease in rCBF was also seen in the
      medial temporal lobe in both the AD and the AAMI subjects compared to the normal
      controls. During the three years of follow up, no cases of dementia were seen in
      the AAMI subjects. However, there were two patients who appeared to have
      difficulty in adapting to daily life due to amnesia, one with a decrease in rCBF
      of the medial temporal lobe on the second SPECT, and the other showing a low rCBF
      the first time. This study suggests that AAMI subjects may comprise both AD and
      normal subjects. Therefore a more prospective study is needed.

PMID- 9594550
TI  - [An evaluation of ischemic stroke using dynamic contrast enhanced perfusion MRI].
AB  - Thrombolytic therapy during the hyperacute stage is important for salvaging dying
      cerebral tissue. To date, however, accurate non-invasive assessment of an
      ischemic lesion during the hyperacute stage has not been possible. Perfusion MRI
      may be the key to the quick diagnosis of ischemic lesions. To assess the
      feasibility of dynamic contrast enhanced perfusion MRI, echo planar imaging was
      performed in 10 patients with ischemic stroke. The relative cerebral blood volume
      (rCBV), mean transit time (MTT), and relative cerebral blood flow(rCBF) were
      measured based on moment analysis and the gamma variate method. These
      measurements, however, are not suitable for the detection of cerebral ischemia
      during the hyperacute stage. Therefore, we additionally studied the changes in a
      concentration curve (time-delta R* curve) of Gd-DTPA, injected into the median
      vein of the forearm. From the curve the SUM (delta R*) time to peak and the delta
      R* peak, which may be calculated quickly, were determined and were compared to
      rCBV, MTT, and rCBF, respectively. The rCBV and the rCBF in the ischemic regions
      were less than those in the contralateral healthy regions (p < 0.05), and the MTT
      in the ischemic regions was longer than that in the contralateral healthy regions
      (p < 0.05). Additionally, SUM (delta R*) and the delta R* peak in the ischemic
      regions were less, and the time to peak in the ischemic regions was longer than
      the value in the contralateral healthy regions (p < 0.05), correlating well to
      the rCBV, rCBF, and MTT measurements. Also, images of these parameters, depicting
      the ischemic lesion earlier than conventional T2 weighted images, can be easily
      made by using an MRI console. These results suggest that the SUM (delta R*), time
      to peak and the delta R* peak images calculated with dynamic contrast enhanced
      perfusion MRI may be one of the best techniques for the detection of cerebral
      ischemic lesions during the hyperacute stage.

PMID- 9594551
TI  - [Association analysis of angiotensin-converting enzyme gene polymorphism with end
      stage renal disease].
AB  - BACKGROUND: Intron 16 insertion/deletion (I/D) polymorphism in the angiotensin
      converting enzyme (ACE) gene may be associated with the progression of renal
      insufficiency in patients with renal diseases. The objective of this study was to
      determine whether D allele is a risk factor for the progression of the disease in
      end-stage renal disease (ESRD) patients. METHODS: Using PCR techniques, genetic
      analysis of the ACE I/D polymorphism was performed on 326 dialysis patients. We
      compared the distribution of genotypes and allele frequency of this polymorphism
      in dialysis patients and the normal Japanese population. The clinical courses of
      47 patients were studied retrospectively, and the progression of chronic renal
      failure using time plots of the reciprocal of serum creatinine (1/Cr) was
      estimated. RESULTS AND CONCLUSION: The frequencies for II, ID, and DD genotypes
      were 134, 148 and 44, respectively. The frequency for I allele was 0.64, and for
      D allele 0.36. These results were similar to the frequencies found in the normal
      Japanese population. However, patients with polycystic kidney disease (PKD)
      showed a high frequency for D allele (0.54: p = 0.023 by chi 2 method). In
      longitudinal courses, we did not find any association between ACE gene
      polymorphism and the declining rate of renal function. However, in patients with
      PKD, the DD genotype may influence the clinical course of renal disease.

PMID- 9594552
TI  - [Quinolinic acid depolarizes the spinal motoneurons of newborn rats by activating
      NMDA receptors].
AB  - Quinolinic acid (QA), a tryptophan metabolite, is known to be present in many
      regions of the mammalian central nervous system (CNS). However, its role is still
      unclear. In order to evaluate the physiological role of QA in CNS, the present
      study was undertaken to examine its action on the spinal motoneurons of newborn
      rats in vitro. It wa found that QA depolarized spinal motoneurons directly. Its
      potency was the same as that of glutamic acid at the same concentrations. The
      depolarization induced by QA was strongly inhibited by 2-amino-5
      phosphonovalerate (AP5), an NMDA receptor antagonist. The effect of quinolinic
      acid was, on the other hand, not inhibited by 6-cyano-7-nitroquinoxaline-2, 3
      dione (CNQX), a non-NMDA receptor antagonist, in the presence of glycerine. These
      results indicate that the NMDA receptor is responsible for the QA-induced
      depolarization. The possible role of QA as a transmitter is discussed.

PMID- 9594553
TI  - [Brain water diffusion coefficients and diffusion anisotropy in non-demented
      patients with diffuse leuko-araiosis].
AB  - PURPOSE: To investigate changes in both water diffusion coefficients and
      diffusion anisotropy in white matter of non-demented patients with leuko-araiosis
      using diffusion-weighted MRI. METHODS: Diffusion mapping was performed on 8 non
      demented patients with leuko-araiosis, 6 patients with chronic cerebral
      infarction and 6 healthy volunteers, using a spin-echo sequence with motion
      probing gradient applied sequentially at two gradient strength settings in three
      orthogonal directions. The apparent diffusion coefficients (ADC) were calculated
      from 4 regions of interest located within the frontal and parietal subcortical
      white matter. The index of diffusion anisotropy (IDA) was calculated from the ADC
      in three orthogonal directions. (IDA = ADCmax-min/ADCmean x 100). RESULTS:
      Significantly larger ADC were found within the frontal and parietal subcortical
      white matter in the non-demented patients with leuko-araiosis (mean = 1.51 +/-
      0.36 x 10(-3) mm2/s) and the were also significantly larger in patients with
      cerebral infarction (mean = 2.12 +/- 0.46 x 10(-3) mm2/s) than in the control
      group (mean = 1.01 +/- 0.33 x 10(-3) mm2/s). But no significant differences were
      found in the IDA between the non-demented patients with leuko-araiosis (mean =
      43.1 +/- 29.2) and the control group (mean = 46.5 +/- 32.5). CONCLUSION: An
      increase in extracellular space caused by the loss of axonal fibers and myelin is
      probably the cause of the higher ADC in periventricular hyperintensity lesions.
      However, the remaining nerve fibers maintain the anisotropy in the lesions in non
      demented patients with leuko-araiosis.

PMID- 9594554
TI  - [Aspiration cytology of liver grafts].

PMID- 9594555
TI  - [Acute aortic dissection. How do we make diagnosis and treat this fatal
      disease?].

PMID- 9594556
TI  - [Prolonged treatment with slow release nicotinic acid in patients with type II
      hyperlipidemia].
AB  - The aim of the study was to compare efficacy and safety of one-year therapy with
      slow-release nicotinic acid (KN-SR) and with ordinary form of the acid (KN). The
      examination was performed in the group of 136 patients with hyperlipidemia-type
      II. KN-SR had satisfactory effectiveness and was much better tolerated than KN.
      During one-year treatment with KN-SR there were observed the decrease of total
      cholesterol (TC) by 18%, LDL-C by 22%, triglycerides by 36%, Lp(a) by 56%, and
      the increase of HDL-C by 12%. The percentage of skin unwanted signs differed
      significantly between KN-group (90.2%) and KN-SR group (24%). Hepatotoxic effects
      were not observed and antipyrine kinetics did not change during one-year
      treatment with slow-release nicotinic acid.

PMID- 9594557
TI  - [Use of immunohistochemical analysis of antigen expression and exfoliative
      cytology of biliary epithelial cells in diagnosis of mechanical jaundice].
AB  - Imaging biliary strictures may suggest malignancy, but cytology can provide final
      diagnosis. In the present evaluation we studied the importance of
      immunohistochemical analysis of antigen expression in sensitivity and specificity
      of cytological evaluation of bile duct epithelium cells. Thirty three patients
      with biliary strictures were examined prospectively. The bile exfoliative
      cytology during endoscopic retrograde cholangio-pancreatography or surgery was
      obtained. Bile specimens were routinely stained with hematoxylin-eosin, examined
      by one experienced cytologist and were reported as positive or negative for
      malignant cells. In addition, the alterations in immunoperoxidase staining of
      carcinoembryonic antigen (mab T84,66), mucin (RA 96), cell membrane antigen (17
      1A) and c-new were assessed. The results revealed a low sensitivity of both-
      traditional exfoliative cytology and the immunohistochemical analysis of antigen
      expression in diagnosis of biliary tract carcinoma (equally 25 and 31%, with the
      specificity of 92%). Appreciation of the samples with simultaneous involvement of
      the both studied methods make possible the diagnosis of the bile duct malignant
      lesions on 7 out of 17 cases (sensitivity 43%) with the specificity of 98%.

PMID- 9594558
TI  - [Circadian urinary excretion of catecholamine, plasma atrial natriuretic peptide,
      endothelin and neuropeptide Y in obese patients with hypertension].
AB  - Obesity increases the risk of developing hypertension by two-to fourfold, with
      more that one third of all cases of hypertension attributable to obesity. The
      present study tested the role of atrial natriuretic peptide (ANP), endothelin-1,2
      (ET-1,2) and neuropeptide Y (NPY) in pathogenesis of obesity hypertension. The
      plasma concentrations of ANP, ET-1,2 and NPY were determined in the peripheral
      venous blood by radioimmunoassay in 27 obese hypertensive patients (group I), in
      24 obese normotensive patients (group II), and in 35 normal subjects (group III).
      RESULTS: Mean plasma ANP was significantly higher in obese than in normal
      subjects. ANP levels were higher in patients group I than in those group II and
      I. In patients of group I plasma ANP concentrations correlated with III BMI and
      mean blood pressure. Plasma levels of ET-1,2 and NPY were similar in patients
      group I, II and III.

PMID- 9594559
TI  - [Relationship between systolic and diastolic function of the left ventricle in
      patients with impaired relaxation of the left ventricle without symptoms of heart
      failure. Attempt at quantitative estimation of diastolic function in the impaired
      relaxation stage].
AB  - Diastolic dysfunction of left ventricle appears very often in patients with
      coronary artery disease (CAD) and hypertension (HT) and is a main cause of heart
      failure in 30-40% of all cases. Relation between systolic and diastolic function
      of left ventricle (LV) is commonly known but not documented well enough.
      Moreover, no quantitative classification of diastolic dysfunction is still
      available. AIM OF THE STUDY: To find out the relations between the parameters of
      systolic and diastolic function of LV in patients with CAD or HT with impaired
      relaxation of LV without symptoms of heart failure and to make up the
      quantitative classification of diastolic dysfunction in the stage of impaired
      relaxation of LV. METHODS: Investigations were carried out in 57 patients (mean
      age 55.5 +/- 11.5) with angiographically proven CAD and in 91 patients (mean age
      56.3 +/- 10.6) with HT and angiographically excluded CAD, all without regional
      myocardial contractility abnormalities and valvular heart diseases. Control group
      consisted of 54 healthy subjects (mean age 55.4 +/- 11.4). During 2D
      echocardiography examination left ventricular end-diastolic (LVEDD) and end
      systolic diameters (LVESD) and left atrial dimension (LA) were obtained. Using
      Doppler method transmitral inflow indices: E velocity (E), A velocity (A), E
      velocity integral (E-VTI), A velocity integral (A-VTI), total velocity integral
      (T-VTI), E deceleration time (DT), isovolumic relaxation time (IVRT) and aortic
      flow velocity integral (Ao-VTI) were measured. Only patients with E/A < or = 1
      and--to exclude pseudonormalization of mitral inflow--with DT > or = 140 ms were
      qualified to the study. We proposed diastolic dysfunction ratio (DDR) calculated
      from formula: DDR = E/A x E-VTI/T-VTI. Using AFVI, LV outflow diameter, heart
      rate (HR) and body surface area cardiac index (CI) was calculated. RESULTS: In
      studied group there were significantly higher values of LA, A, IVRT, DT and lower
      values of E, E/A, E-VTI and DDR compared to controls. There were no significant
      differences between these groups in HR, LVEDD, LVESD, T-VTI and CI. No
      significant differences in any of studied parameters were found between subgroups
      with CAD and HT. Among healthy subjects in subgroup with abnormal mitral inflow
      pattern (E/A < or = 1) there were significantly higher values of LA, IVRT, DT and
      lower values of DDR than in sugroup with normal one. Both subgroups did not
      differ in LVEDD, LVESD, CI. In the studied group there was positive correlation
      between DDR and CI (r = 0.69, p < 0.001), DDR and IVRT (r = 0.71, p < 0.001), DDR
      and DT (r = 0.61, p < 0.001), CI and E (r = 0.34, p < 0.01), CI and IVRT (r =
      0.52, p < 0.001), CI and DT (r = 0.42, p < 0.001), CI and E/A (r = 0.54, p <
      0.001), CI and E-VTI (r = 0.43, p < 0.001). In the control group significant
      correlation was found only between DDR and IVRT (r = 0.64, p < 0.02) and between
      DDR and DT (r = 0.52, p < 0.02) but not between DDR and CI. Using DDR DD was
      divided into 3 classes: class I with DDR > 0.47, class II with 0.47 > or = 0.30,
      and class III with DDR < 0.30. Applying of such intervals of values of DDR
      determined the groups which significantly differed between themselves in CI, IVRT
      and DT. CONCLUSIONS: (1) In patients with CAD or HT with impaired relaxation of
      LV without symptoms of heart failure there is relation between parameters of
      systolic and diastolic function of LV: the more advanced diastolic dysfunction,
      the more impaired systolic function. (2) In healthy subjects there is no relation
      between parameters of systolic and diastolic function of LV. (3) DDR is a good
      indicator of quantitative estimation of diastolic dysfunction in the stage of
      impaired relaxation of LV.

PMID- 9594560
TI  - [Expression of platelet activation markers--selectin P and glycoprotein CD63
      during hemodialysis].
AB  - The bleeding tendency is a common feature of chronic uremia. Abnormalities of
      platelet function play a role in the pathogenesis of this disorder. A direct
      contact between platelets and an artificial dialysis membrane results in strong
      activation of thrombolysis. The aim of our study was to investigate platelets
      activation in vivo during haemodialysis. We used monoclonal antibodies specific
      against platelet activation markers--selectin P (CD62) and glycoprotein CD63. The
      expression of those antigens was analyzed by flow cytometry. Blood samples were
      obtained from 20 long-term haemodialysed patients with end-stage renal disease.
      After 15 minutes of haemodialysis the expression of CD62 and CD63 was
      significantly higher (p < 0.001) as compared CD63 glycoprotein. Our results show
      that haemodialysis has a significant influence on platelet activation and can
      favour co-existence of the bleeding tendency and the prothrombotic status in long
      term hemodialyzed patients.

PMID- 9594561
TI  - [Prophylaxis after occupational exposure to human immunodeficiency virus (HIV)].
AB  - Reasons for seeking consultation among health care workers due to potential or
      supposed risk of HIV infection were analyzed. From August 1990 till July 1996 41
      health care providers were consulted including: 22 nurses, 1 student of nursing
      college, 3 midwives, 4 laboratory workers and 7 physicians (surgeons and
      gynaecologist). Type of exposure to HIV and applying of safety precautions were
      evaluated in each case. In 10 cases the offer of postexposure prophylaxis with
      zidovudine was accepted (6 nurses, 1 student of nursing college, 3 surgeons).
      Exposure to HIV was described as: needlestick immediately after it was used in a
      HIV/AIDS patient, injury with a surgical needle while operating on an HIV
      infected blood. In the remaining cases the fear of HIV infection was due to work
      without protective gloves (nurses, laboratory workers), performing surgery on HIV
      (+) patient, (surgeons, nurses) or short-time contact of HIV infected blood with
      undamaged skin (nurses). Following conclusions can be drawn from our study: 1.
      Health care workers undertake safety precautions only when they are informed
      about HIV seropositivity of the patient. 2. Patients whose HIV serologic status
      is not known are considered not to create health risk for medical staff. 3. The
      level of knowledge of health care workers about risk of acquiring HIV infection,
      lack of risk and ways of diminishing the risk is poor. 4. None of followed health
      care workers was HIV-seropositive after occupational exposure to HIV.

PMID- 9594563
TI  - [Ehlers-Danlos syndrome type VII--case report].
AB  - We described a 30-year old man with Ehlers-Danlos syndrome type VI, manifested by
      marked kyphoscoliosis and severe myopia, who was admitted to our department
      because of chest pain. Abnormalities of stature and joint system along with eye
      changes, occurred starting from the birth and they aggravated gradually. Signs of
      increased fragility of the skin blood vessels appeared during childhood. At the
      age of 26 years, the patient suffered from a spontaneous rupture of the right
      brachial artery. Spirometry revealed marked restrictive ventilatory
      insufficiency, which at present constitutes the predominant health risk for the
      patient.

PMID- 9594562
TI  - [Recurrent pulmonary embolism in an athlete. Vena cava filter implantation as a
      effective alternative to medical treatment].
AB  - The case of 63 years old judo trainer, actively working and suffering from
      pulmonary embolism originating from deep vein thrombosis aggravated by sport
      traumas, is presented. Repeated episodes of pulmonary embolism, despite treatment
      with oral anticoagulants, have led to alternative method of treatment--vena cava
      filter insertion. Diagnosis achieving process, concerning the sportive lifestyle,
      and the effectiveness of pharmacological treatment, are discussed.

PMID- 9594564
TI  - [Intraperitoneal administration of drugs in patients treated with peritoneal
      dialysis].

PMID- 9594565
TI  - [Problems with food intake and nutritional status in patients treated with
      continuous ambulatory peritoneal dialysis (CAPD)].

PMID- 9594566
TI  - [Postpartum thyroid disfunction syndrome].

PMID- 9594567
TI  - [Secondary hypertension in the elderly].

PMID- 9594568
TI  - [Professor Jerzy Kosowicz--life and achievements of the honorary member of the
      Polish Society of Internal Medicine].

PMID- 9594569
TI  - Bacillus thuringiensis insecticidal proteins: molecular mode of action.
AB  - Growing interest in biorational pesticides has placed the Bacillus thuringiensis
      insecticidal crystal proteins at the forefront of pesticides for plant genetic
      engineering. The development of improvement pesticides, both in enhanced activity
      and broader host range, depends on an understanding of its mechanism of action.
      This review presents a complete overview of the bacterium and the group of
      insecticidal proteins known as Cry proteins or delta-endotoxins. The molecular
      mode of action is described in detail, including the mapping of receptor binding
      sites by site-directed mutagenesis, the known receptors, and the ion-channel
      activity of the toxins.

PMID- 9594571
TI  - Eukaryotic translation elongation factor 1 alpha: structure, expression,
      functions, and possible role in aminoacyl-tRNA channeling.
AB  - This review offers a comprehensive analysis of eukaryotic translation elongation
      factor 1 (eEF-1 alpha) in comparison with its bacterial counterpart EF-Tu.
      Altogether, the data presented indicate some variances in the elongation process
      in prokaryotes and eukaryotes. The differences may be attributed to translational
      channeling and compartmentalization of protein synthesis in higher eukaryotic
      cells. The functional importance of the EF-1 multisubunit complex and expression
      of its subunits under miscellaneous cellular conditions are reviewed. A number of
      novel functions of EF-1 alpha, which may contribute to the coordinate regulation
      of multiple cellular processes including growth, division, and transformation,
      are characterized.

PMID- 9594570
TI  - Transcription activation and repression by interaction of a regulator with the
      alpha subunit of RNA polymerase: the model of phage phi 29 protein p4.
AB  - Regulatory protein p4, encoded by Bacillus subtilis phage phi 29, has proved to
      be a very useful model to analyze the molecular mechanisms of transcription
      regulation. Protein p4 modulates the transcription of phage phi 29 genome by
      activating the late A3 promoter (PA3) and simultaneously repressing the two main
      early promoters, A2b and A2c (or PA2b and PA2c). This review describes in detail
      the regulatory mechanism leading to activation or repression, and discusses them
      in the context of the recent findings on the role of the RNA polymerase alpha
      subunit in transcription regulation. Activation of PA3 implies the p4-mediated
      stabilization of RNA polymerase at the promoter as a closed complex. Repression
      of the early A2b promoter occurs by binding of protein p4 to a site that
      partially overlaps the -35 consensus region of the promoter, therefore preventing
      the binding of RNA polymerase to the promoter. Repression of the A2c promoter,
      located 96 bp downstream from PA2b, occurs by a different mechanism that implies
      the simultaneous binding of protein p4 and RNA polymerase to the promoter in such
      a way that promoter clearance is inhibited. Interestingly, activation of PA3 and
      repression of PA2c require an interaction between protein p4 and RNA polymerase,
      and in both cases this interaction occurs between the same surface of protein p4
      and the C-terminal domain of the alpha subunit of RNA polymerase, which provides
      new insights into how a protein can activate or repress transcription by subtle
      variations in the protein-DNA complexes formed at promoters.

PMID- 9594572
TI  - Type X collagen and other up-regulated components of the avian hypertrophic
      cartilage program.
AB  - Elucidating the cellular and molecular processes involved in growth and
      remodeling of skeletal elements is important for our understanding of congenital
      limb deformities. These processes can be advantageously studied in the epiphyseal
      growth zone, the region in which all of the increase in length of a developing
      long bone is achieved. Here, young chondrocytes divide, mature, become
      hypertrophic, and ultimately are removed. During cartilage hypertrophy, a number
      of changes occur, including the acquisition of synthesis of new components, the
      most studied being type X collagen. In this review, which is based largely on our
      own work, we will first examine the structure and properties of the type X
      collagen molecule. We then will describe the supramolecular forms into which the
      molecule becomes assembled within tissues, and how this changes its physical
      properties, such as thermal stability. Certain of these studies involve a novel,
      immunohistochemical approach that utilizes an antitype X collagen monoclonal
      antibody that detects the native conformation of the molecule. We describe the
      developmental acquisition of the molecule, and its transcriptional regulation as
      deduced by in vivo footprinting, transient transfection, and gel-shift assays. We
      provide evidence that the molecule has unique diffusion and regulatory properties
      that combine to alter the hypertrophic cartilage matrix. These conclusions are
      derived from an in vitro system in which exogenously added type X collagen moves
      rapidly through the cartilage matrix and subsequently produces certain changes
      mimicking ones that have been shown normally to occur in vivo. These include
      altering the cartilage collagen fibrils and effecting changes in proteoglycans.
      Last, we describe the subtractive hybridization, isolation, and characterization
      of other genes up-regulated during cartilage hypertrophy, with specific emphasis
      on one of these--transglutaminase.

PMID- 9594573
TI  - Domains of human topoisomerase I and associated functions.
AB  - Human topoisomerase I can be divided into four domains based on homology
      alignments, physical properties, sensitivity to limited proteolysis, and fragment
      complementation studies. Roughly the first 197 amino acids represent the N
      terminal domain that appears to be devoid of secondary structure and is likely
      important for targeting the enzyme to its sites of action within the nucleus of
      the cell. The core domain encompasses residues approximately 198 to approximately
      651, is involved in catalysis, and is important for the preferential binding of
      the enzyme to supercoiled DNA. The C-terminal domain extends from residue
      approximately 697 to the end of the protein at residue 765 and contains the
      catalytically important active site tyrosine at position 723. The core and C
      terminal domains are connected by a poorly conserved, protease-sensitive linker
      domain (residues approximately 652 to approximately 696) that has been implicated
      in DNA binding and may influence how long the enzyme remains in the nicked
      stated. Mutations that confer resistance to the topoisomerase I poison
      camptothecin are located in the core and C-terminal domains and presumably
      identify residues important for drug binding.

PMID- 9594574
TI  - Autoregulation of eukaryotic transcription factors.
AB  - The structures of several promoters regulating the expression of eukaryotic
      transcription factors have in recent years been examined. In many cases there is
      good evidence for autoregulation, in which a given factor binds to its own
      promoter and either activates or represses transcription. Autoregulation occurs
      in all eukaryotes and is an important component in controlling expression of
      basal, cell cycle specific, inducible response and cell type-specific factors.
      The basal factors are autoregulatory, being strictly necessary for their own
      expression, and as such must be epigenetically inherited. Autoregulation of
      stimulus response factors typically serves to amplify cellular signals
      transiently and also to attenuate the response whether or not a given inducer
      remains. Cell cycle-specific transcription factors are positively and negatively
      autoregulatory, but this frequently depends on interlocking circuits among family
      members. Autoregulation of cell type-specific factors results in a form of
      cellular memory that can contribute, or define, a determined state.
      Autoregulation of transcription factors provides a simple circuitry, useful in
      many cellular circumstances, that does not require the involvement of additional
      factors, which, in turn, would need to be subject to another hierarchy of
      regulation. Autoregulation additionally can provide a direct means to sense and
      control the cellular conce]ntration of a given factor. However, autoregulatory
      loops are often dependent on cellular pathways that create the circumstances
      under which autoregulation occurs.

PMID- 9594575
TI  - Development of more efficacious antibodies for medical therapy and diagnosis.
AB  - Two procedures for improving the efficacy of medically important antibodies are
      described. The first procedure is designed to reduce the immunogenicity of
      nonhuman antibodies to the barest minimum--the "humanization" is accomplished by
      transplanting only the specificity-determining residues of the nonhuman antibody
      onto a human antibody template. The second procedure is designed to permit the
      easy production of multispecific/multivalent antibodies via heterodimer formation
      of electrostatically complementary Fc regions.

PMID- 9594576
TI  - Molecular regulation of insulin-like growth factor-I and its principal binding
      protein, IGFBP-3.
AB  - The insulin-like growth factors (IGFs) have diverse anabolic cellular functions,
      and structure similar to that of proinsulin. The distribution of IGFs and their
      receptors in a wide variety of organs and tissues enables the IGFs to exert
      endocrine, paracrine, and autocrine effects on cell proliferation and
      differentiation, caloric storage, and skeletal elongation. IGF-I exhibits
      particular metabolic responsiveness, and circulating IGF-I originates
      predominantly in the liver. Hepatic IGF-I production is controlled at the level
      of gene transcription, and transcripts are initiated largely in exon 1. Hepatic
      IGF-I gene transcription is reduced in conditions of protein malnutrition and
      diabetes mellitus, and our laboratory has used in vitro transcription to study
      mechanisms related to diabetes. We find that the presence of sequences downstream
      from the major transcription initiation sites in exon 1 is necessary for the
      diabetes-induced decrease in IGF-I transcription. Six nuclear factor binding
      sites have been identified within the exon 1 downstream region, and footprint
      sites III and V appear to be necessary for metabolic regulation; region V probes
      exhibit a decrease in nuclear factor binding with hepatic nuclear extracts from
      diabetic animals. IGFs in biological fluids are associated with IGF binding
      proteins, and IGFs circulate as a 150-kDa complex that consists of an IGF, an
      IGFBP-3, and an acid-labile subunit. Circulating IGFBP-3 originates mainly in
      hepatic nonparenchymal cells, where IGF-I increases IGFBP-3 mRNA stability, but
      insulin increases IGFBP-3 gene transcription. Regulation of IGFBP-3 gene
      transcription by insulin appears to be mediated by an insulin-responsive element,
      which recognizes insulin-responsive nuclear factors in both gel mobility shift
      assays and southwestern blots. Studies of mechanisms underlying the modulation of
      IGF-I and IGFBP-3 gene transcription, and identification of critical nuclear
      proteins involved, should lead to new understanding of the role and regulation of
      these important growth factors in diabetes mellitus and other metabolic
      disorders.

PMID- 9594577
TI  - Molecular genetics of succinate:quinone oxidoreductase in eukaryotes.
AB  - Succinate:quinone oxidoreductase is a membrane-associated complex in
      mitochondria, often referred to as complex II, based on the fractionation scheme
      developed by Y. Hatefi and colleagues. It consists of four peptides, two of which
      are integral membrane proteins (15 and 12-13 kDa, respectively) and two others
      that are peripheral membrane proteins, i.e., a flavoprotein (Fp, 70 kDa) and an
      iron-protein (Ip, 27 kDa). The mature, functional complex contains a cytochrome
      in association with the membrane proteins, a flavin linked covalently to the
      largest peptide, and three iron-sulfur clusters in the 27-kDa subunit. The
      present review touches only briefly on the biochemical and biophysical properties
      of this complex. Instead, the focus is on the molecular-genetic studies that have
      become possible since the first genes from eukaryotes were cloned in 1989. The
      evolutionary conservation of the amino acid sequence of both the Fp and the Ip
      peptides has facilitated the cloning of these genes from a large variety of
      eukaryotic organisms by PCR-based methods. The review addresses questions related
      to the regulation of the expression of these genes, with an emphasis on mammals
      and yeast, for which most of the information is available. Four different genes
      have to be co-ordinately regulated. Transcriptional as well as
      posttranscriptional regulatory mechanisms have been observed in diverse
      organisms. Intriguing observations have been made in studies of this enzyme
      during the life cycle of organisms existing alternately under aerobic and
      anaerobic conditions. Naturally occurring or induced mutations in these genes
      have shed light on several questions related to the assembly of this complex, and
      on the relationship between structure and function. Four different peptides are
      imported into the mitochondria. They have to be modified, folded, and assembled.
      The stage is set for the exploration of highly specific changes introduced by
      site-directed mutagenesis. Until recently the genes were believed to be
      exclusively nuclear in all eukaryotes, but exceptions have since been found. This
      finding has relevance in the discussion of the evolution of mitochondria from
      prokaryotes. A highly conserved set of genes is found in prokaryotes, and some
      informative comparisons on gene organization and expression in prokaryotes and
      eukaryotes have been included.

PMID- 9594578
TI  - Regulation of fat synthesis and adipose differentiation.
AB  - Adipocytes have highly specialized function of accumulating fat as stored energy
      that can be used during periods of food deprivation. The process of fat synthesis
      and development of adipose tissue are under hormonal and nutritional control.
      This review first describes transcription of the two critical enzymes involved in
      fat synthesis, fatty acid synthase and mitochondrial glycerol-3-phosphate
      acyltransferase, is decreased to an undetectable level during fasting. Food
      intake, especially a high carbohydrate, fat-free diet, subsequent to fasting
      causes dramatic increase in transcription of these genes. Insulin secretion is
      increased during feeding, having a positive effect, whereas cAMP, which mediates
      the effect of glucagon which increases during fasting, has a negative effect on
      transcription of these genes. Using adipocytes in culture and in transgenic mice
      that express liciferase driven by the fatty acid synthase promoter, cis-acting
      and trans-acting factors that may mediate the transcriptional regulation were
      examined. Upstream stimulatory factors (USFs) that bind to -65 E-box are required
      for insulin-mediated transcriptional activation of the fatty acid synthase gene.
      This review next describes how pref-1 is a novel inhibitor of adipose
      differentiation and is a plasma membrane protein containing six EGF-repeats in
      the extracellular domain. Pref-1 is highly expressed in 3T3-L1 preadipocytes, but
      is not detectable in mature fat cells. Down regulation of pref-1 is required for
      adipose differentiation, and constitutive expression of pref-1 inhibits
      adipogenesis. Moreover, the ectodomain of pref-1 is cleaved to generate a
      biologically active 50 kDa soluble form. There are four major forms of membrane
      pref-1 resulting from alternate splicing, but two of the forms with a larger
      deletion do not produce biologically active soluble form, indicating that
      alternate splicing determines the range of action, juxtacrine or paracrine, of
      the pref-1.

PMID- 9594579
TI  - [PTSD as a result of a natural disaster].
AB  - A review of modern conceptions that may help in diagnosing of PTSD in the victims
      of flood in Poland in July 1997 was made. Diagnostic, epidemiological and
      prognostic problems in the development of the disorder were discussed.

PMID- 9594580
TI  - [Depressive symptoms in active phase of paranoid schizophrenia. Part I: Their
      link to negative symptoms].
AB  - The studies dealt with the relationships between negative and depressive
      symptomatology in the active phase of paranoid schizophrenia and were aimed at
      distinguishing the symptoms of the greatest power discriminating either category
      of symptoms.

PMID- 9594581
TI  - [Depressive symptoms in active phase of paranoid schizophrenia. Part II: Their
      link to positive symptoms].
AB  - 66 inpatients who met the DSM-III-R and ICD-10 criteria for paranoid
      schizophrenia-active phase were assessed using the SAPS and CDS in order to
      establish interrelations between depressive and positive symptomatology. The
      results were then analyzed in reference do particular items of the scale CDS and
      the three stages of examinations. Numerous positive correlations were found
      between depressive symptoms and the symptoms from the subscale of Delusions and
      Hallucinations SAPS (Delusions of Sin or Guilt, of Mind Reading, of Being
      Controlled, of Reference, Somatic Delusions and Hallucinations) and negative
      correlations with the symptoms from the subscale of Positive Formal Thought
      Disorder.

PMID- 9594582
TI  - [Evaluation of depressive syndromes in the course of schizophrenia with the use
      of Calgary scale in patients from the inpatient hospital care].
AB  - Among 98 schizophrenic patients consecutively admitted to day hospital during the
      period of one year, the presence of depressive syndrome diagnosed with the use of
      Calgary Depression Scale was established in 39% of patients. The intensity of
      depression was higher in the patients' than in the investigators' evaluation.
      After therapy at day hospital, which lasted 3.7 months on average, the repeated
      clinical evaluation showed significant decrease of all depressive symptoms as
      well as schizophrenia psychopathology. In 29% of patients there were no symptoms
      of depression at discharge from the day hospital. In 66%, the depressive symptoms
      which were most severe at admission, i.e. depressive mood, hopelessness and
      guilty ideas of reference, showed most distinct diminution after treatment.

PMID- 9594583
TI  - [Dynamics of family picture in graphic works by paranoid schizophrenic patients].
AB  - An analysis of pathographization of form and content of examined drawings of
      families made before treatment and after treatment was performed in a group of
      patients treated with clozapine, and in a group of patients treated with
      phenotiazine derivatives.

PMID- 9594584
TI  - [Social networks of schizophrenic patients three years after the first
      psychiatric hospitalization. Differences between a group treated in psychosocial
      program and patients treated in an individual treatment program].
AB  - Social networks of 54 DSM-III schizophrenic patients were studied. There are
      differences between social networks of patients who took part in the psychosocial
      program (n = 23) and social networks of patients treated in individual treatment
      program (n = 31). Patients treated in the psychosocial program receive
      significantly more social support from their social networks and there are
      significantly more new relationships in their networks than in the networks of
      patients treated in individual treatment program.

PMID- 9594585
TI  - [The Yale-Brown Scale: instrument for assessing the severity of obsessive
      compulsive disorders].
AB  - The paper presents characteristics and evaluation of the Yale-Brown Scale, its
      clinical value in assessing severity of obsessive compulsive disorders. The Yale
      Brown Scale is a semistructured interview. The scale consists of 10 items, rated
      from 0 (no symptoms) to 4 (extreme symptoms). There are separate ratings for
      severity of obsessions and compulsions. The assessment of items is based on the
      patient's report and the clinician's observations gained during the interview.
      The studies indicate that the Yale-Brown Scale is a reliable and valid instrument
      for assessing severity of obsessive compulsive disorder symptoms in patients with
      obsessive compulsive disorder. This instrument is sensitive enough to changes in
      symptoms severity; thus, it permits to analyse the efficacy of treatment of OCD.
      The fact that the total score is not determined by the type of obsessive
      compulsive symptoms, permits to compare the symptoms severity in patients with
      different types of obsessions and compulsions and it is suitable to assess the
      efficacy of treatment of different types of obsessive compulsive disorder.

PMID- 9594586
TI  - [Obsessive-compulsive disorder in children and adolescents: a literature review.
      Part II].
AB  - This paper presents opinions about obsessive-compulsive disorder in children and
      adolescents. Washing, checking, repeating, touching, counting and scrupulosity
      are the most commonly seen rituals. Almost all patients reported a change in
      their principal symptom over time. There appear to be no significant
      intercultural differences in phenomenology. Childhood OCD seems to be associated
      with depression, eating disorders and anxiety disorders (in several cases the
      secondary diagnosis was mild), whereas there seems to be no convincing relation
      between OCD and schizophrenia. Follow-up studies of the course of OCD with a
      childhood onset are still very few in number. OCD is disabling disorder with bad
      prognosis for one third to one half of the patients. The behavior therapy is an
      effective treatment for childhood-onset OCD, while numerous systematic
      investigations have demonstrated the efficacy of clomipramine treatment.
      Fluoxetine and other drugs which inhibit serotonin reuptake also may be helpful.

PMID- 9594588
TI  - [The case of central pontine myelinolysis in an alcohol dependent male].
AB  - Long-term alcohol abuse can lead to numerous central nervous system lesions,
      among them central pontine myelinolysis. In this paper, the first in Polish
      literature case of central pontine myelinolysis in an alcohol dependent male,
      clinically diagnosed, and confirmed by nuclear magnetic resonance with one year
      follow-up has been presented. The patient, 49 years old, was admitted to
      Addiction Treatment Unit, Department of Psychiatry in Bydgoszcz. After admission
      he manifested clouded consciousness, dysphasia, hyponatremia and
      neuropsychological abnormalities which showed brain stem lesion. He had no
      significant abnormalities in CT. Nuclear magnetic resonance revealed triangular
      hypointensive lesion 10 x 5 mm in central pontine region. One year after
      admission to Addiction Treatment Unit he still has troubles with walking and
      swallowing. He has bilateral pyramidal symptoms and emotional lability. He was
      treated with vinpocetine (0.075 g per day), piracetam (4.8 g per day) and
      chlorprotixen (0.09 g per day). He was admitted to Psychiatric Ward because of a
      suicidal attempt as a manifestation of mood disorder due to general medical
      condition.

PMID- 9594587
TI  - [Nicotine dependence and health care issues with special emphasis on mental
      health].
AB  - Nicotine dependence is discussed as a separate health problem on the basis of
      historical facts and contemporary studies. Coexistence of nicotine dependence and
      many psychopathological symptoms is indicated. Possible connections between
      smoking and psychiatric disorders are considered.

PMID- 9594589
TI  - [Familial metachromatic leukodystrophy as a cause of psychotic manifestations in
      young adults].
AB  - Cases of metachromatic leucodystrophy in brother and sister are presented. The
      clinical pattern in the female was characterised by the progressing dementia,
      whereas in the male the first symptom was the manic syndrome. The neurological
      status was normal. The cases were diagnosed by the demyelination visible in MRI
      pattern and in the decreased activity of arylsulphatase A in blood leukocytes.

PMID- 9594590
TI  - [Chaux-de-Fonds hospital: from charity hospital to modern hospital].

PMID- 9594591
TI  - [Doctor Fritz de Quervain at Chaux-de-Fonds (1894-1910)].

PMID- 9594592
TI  - [Surgery for severe obesity: some reflections on an evolving field].

PMID- 9594593
TI  - [Endoscopic surgery of the upper limb].

PMID- 9594594
TI  - [Survival and quality of life after a stay in intensive care].

PMID- 9594595
TI  - [Antibiotics and some popular beliefs].
AB  - Although rarely studied, popular beliefs play a role in treatment compliance. In
      order to clarify this problem in the field of anti-infectious agents we sent a
      questionnaire to 200 patients and 100 nurses of the community hospital in La
      Chaux-de-Fonds, Switzerland. We tried to test the influence, in poor patient
      compliance, of wrong beliefs concerning side effects and drug elimination. Eleven
      and twenty percent of patients suffered at least once from an episode of
      "allergy" and from another possible side effect respectively. Fatigue, often
      mentioned, has not been proved being a side effect and allergy is vastly
      overdiagnosed. Almost 50% of patients believe that antibiotics remain in the
      organism for months. Nurses are more intolerant to antibiotics than patients. In
      order to gain some insight on the role of cultural differences, the same
      questionnaire was submitted to nurses of the Moubda hospital in Cameroun. Their
      answers are very different from those of their swiss collegues: less side effects
      and allergies are reported. Nevertheless 17% would refuse an antibiotic therapy
      in case of a severe infection as compared to only 8% of swiss nurses. The reason
      for theses differences warrants further study.

PMID- 9594596
TI  - [Epidermoid cancer of the esophagus: role of radiotherapy and chemotherapy].

PMID- 9594597
TI  - [Dacryocystorhinostomy by nasal endoscopy: an example of multidisciplinary
      collaboration].
AB  - The authors report on endonasal dacryocystorhinostomy: 19 operations have been
      done (5 pre-saccal stenosis and 14 post-saccal stenosis). Operations on pre
      saccal pathways allow to reduce significantly the tearing, without suppressing it
      completely. Surgery of the post-saccal pathways gives the best results, with the
      suppression of the tearing or/and of the superinfection in almost all cases. The
      pathology of the excretory lacrymal pathways, the surgical technique and the
      detailed results will be presented.

PMID- 9594601
TI  - [Pediatric resuscitation: experiences at Chaux-de-Fonds during eighteen months].

PMID- 9594600
TI  - [Torticollis in the newborn. A case presentation and review of the literature].
AB  - Contracture of the sternocleidomastoide muscle observed in the newborn is a well
      known entity but it's pathogenesis remains controversial. We present a typical
      case and review the literature on this condition.

PMID- 9594598
TI  - [Is there a role for functional sinus surgery in children?].
AB  - This retrospective study is based on 16 children operated for Functional
      Endonasal Sinus Surgery (FESS) in the ENT division of the La Chaux-de-Fonds
      Hospital. We discuss pathologies predisposing to chronic sinusitis, their medical
      and surgical treatment. Finally the results of Functional Endonasal Sinus Surgery
      in this study is compared to the findings in other studies in the current
      literature.

PMID- 9594599
TI  - [Facial paralysis during pregnancy].
AB  - We have been confronted in our centre with numerous cases of Bell's palsy in the
      pregnant patient. The aetiology of this lesion is discussed. A typical case is
      exposed.

PMID- 9594602
TI  - [Scleroderma: some considerations from a case report].

PMID- 9594603
TI  - [Fabrication of cidofovir ampules for intravitreal injections for cytomegalovirus
      retinitis].

PMID- 9594605
TI  - [Research and society: a liberty to guard?].

PMID- 9594604
TI  - [Vitamin D and its active metabolites in the prevention and treatment of
      osteoporosis].

PMID- 9594607
TI  - [History of salt].

PMID- 9594608
TI  - [Annular skin lesions, bulls-eye or rosette].

PMID- 9594610
TI  - [Pseudo-alcoholic hepatitis and cirrhosis caused by amiodarone (Cordarone)].
AB  - Amiodarone is an antiarrhythmic drug widely used to treat a variety of
      supraventricular and ventricular arrhythmias. However its drawback is a very slow
      elimination and very frequent adverse effects (thyroid, pulmonary, neurologic,
      ocular, dermatologic, hepatic disorders). We describe a patient who developed a
      pseudoalcoholic liver disease and a cirrhosis after use of Amiodarone for a long
      period of time.

PMID- 9594609
TI  - [How I treat...Raynaud's phenomenon].
AB  - Raynaud's phenomenon is a paroxysmal vasospasm affecting the extremities,
      particularly the fingers. The idiopathic type is the most frequently encountered
      and the secondary types have multiple origins. The mainstay of treatment relies
      on hygieno-dietetic measures. When they fail, calcium antagonists, sustained
      release transdermal glyceryl trinitrate and a few other vasoactive drugs may
      prove to be effective. However, side effects may limit their prescription.

PMID- 9594611
TI  - [Treatment of epithelial ovarian cancer].
AB  - Cancer of the ovary is much less frequent than breast cancer. Nevertheless, it
      hits 12 women out of 1,000,000 every year. The majority of patients are diagnosed
      with the disease in their fifties. The usual prognosis for ovarian cancer is
      back. Indeed, in 70 percent of all cases, it is, unfortunately, discovered at an
      advanced stage. This article will discuss the medical therapeutic approaches to
      ovary cancer, while stressing that major surgery is the basic treatment. If
      hormonotherapy and immunotherapy have not so far proven their efficacy,
      chemotherapy treatment has shown its ability to combat this affliction.

PMID- 9594614
TI  - [Prematurity: current role of prostaglandin synthesis inhibitors].
AB  - Prostaglandins seem to play a significant role in labor initiation; it is not
      surprising therefore that inhibitors of prostaglandin synthesis have been studied
      for the treatment of premature contractions. Controlled studies confirmed the
      tocolytic effect of indomethacin which is better tolerated than other drugs used
      in the same indication. Possible foeto-neonatal complications prevent a wider use
      of indomethacin. If it is given before the 32nd week of pregnancy and for less
      than 72 hours, the risks are acceptable. In other cases, the expected advantages
      and possible hazards should be carefully weighed and intensive foeto-neonatal
      care is required. Characterization of the phospholipases and cyclo-oxygenases
      specific to preterm labor will undoubtedly allow to design, in the future, a more
      appropriate therapeutic approach.

PMID- 9594612
TI  - [Psychosocial environment and premature birth].
AB  - For about twenty years, prematurity has been the subject of many preventive
      actions. In spite of the elaboration of different screening programmes, preterm
      deliveries rate doesn't decrease. Some somatic risk factors are now known and are
      the subject of an unconditional screening in prenatal consultation. However we
      consider that the etiology of many preterm deliveries remain unknown and 55% of
      preterm cases could be idiopathic without any explanation of pathological order.
      The clinical observation suggests the existence of a link between preterm
      delivery and the psychosocial environment of the pregnant woman. According to
      that suggestion, they are now making a study in the university obstetrical
      service of the CHR Citadelle (Liege). The first part of the research has enabled
      to identify different risk factors such as: illegitimate pregnancy, future mother
      living alone, unemployed husband, no wage, stress, earlier miscarriage, social
      isolation, less than 2 years between 2 babies, bad satisfying pregnancy on a
      psychological and/or physical point of view. According to the study and
      literature results, a psychosocial risk screening overview has been elaborated.
      It would permit to identify the cases leading surely to a preterm delivery. That
      study is financed by a convention between the "Ministere de la Culture et des
      Affaires sociales de la Communaute francaise".

PMID- 9594615
TI  - [Activity of street drugs].
AB  - In the seized samples, the concentrations of diamorphine (heroin) varied from
      zero to more than seventy percent and the concentrations of cocaine from zero to
      more than ninety percent. Such variations in concentrations of active
      constituents constitute a major risk for those who use and abuse street drugs.

PMID- 9594617
TI  - [Measurement of arterial pressure].
AB  - The casual determination of blood pressure remains the basis of the diagnosis of
      arterial hypertension and the criteria for usefulness of drug therapy. The
      reference values usually in use concern determinations by the doctor in very well
      defined conditions, rest, size of the bladder, etc.... The poor reproductibility
      of the determinations made by the doctor in casual conditions has produced a
      large interest for new approaches: autodetermination by the patient at home, and
      ambulatory blood pressure determinations using automatic devices. These new
      approaches have their own reference values, specific indications and limitations.

PMID- 9594613
TI  - [Mortality and morbidity of low birth weight premature newborns in a French
      community from 1990 to 1994].
AB  - The development of new technologies in neonatal intensive care which appeared
      this last decade increased the viability of premature newborns and contributed to
      the increase in the number of admissions of very low birth weight (VLBW) newborns
      in the intensive neonatal care services (12.6% of admissions in 1987, 15.2% in
      1996). In a retrospective epidemiology survey in French speaking Belgian
      Community, we collected the data of 1521 newborns whose birth weight was under
      1500 g, from January 1990 to December 1994, in order to improve our knowledge or
      regional mortality and morbidity rates and to estimate the impact of new
      procedures. We do not notice any variation of annual mortality (+/- 20%), nor of
      morbidity (sequelae risks to survivors at the departure of the hospital +/- 23%)
      on the global population during the survey period. However the mortality of
      infants born between 30 and 33 weeks drops dramatically (17% in 1990, 3.6% in
      1994). As it has been demonstrated in randomised surveys, we recover the
      beneficial effect of antenatal corticotherapy which allows us to reduce to more
      than 50% the mortality of newborns from treated mothers (11% mortality versus
      24%). In comparison to figures of international literature, our survival rate
      without sequelae is at least 10% lower than American results for infants whose
      birth weight is < 1000 g and at least 5% lower for infants between 1000 and 1500
      g. In conclusion, although the introduction of surfactant and high frequency
      ventilation during this period, mortality rate of VLBW infants doesn't seem to
      decrease significantly from 1990 to 1994. However, multivariate statistical study
      of predictable mortality and morbidity factors need to be performed in order to
      define or promote preventive strategy.

PMID- 9594616
TI  - [Vascular surgery in octogenarians].
AB  - The prevalence of peripheral vascular disease increases with aging of the
      population. About 8% of the octogenarians present significant carotid artery
      stenosis, about 4% have an abdominal aortic anneurysm of 40 mm or more, and 6%
      suffer critical limb ischemia. Carotid endarterectomy in octogenarians is a
      valuable tool for stroke prevention, only if the combined perioperative stroke
      mortality rate is lower than 3%. Operating an abdominal aneurysm of 50 mm or more
      in octogenarians is characterized by an operative mortality that is higher
      compared to that observed in a younger patient group (4.7% vs 2.7%). Aneurysm
      surgery remains nevertheless justified, since it is the only way to prevent the
      evolution to rupture, that is almost fatal. Limb salvage surgery should always be
      considered for an 80-years patient with critical limb ischemia, since
      readaptation after major limb-amputation is not evident for octogenarians. An
      extensive review of literature is presented concerning vascular aging and results
      of carotid surgery, aneurysm repair and lower limb revascularization in
      octogenarians. The authors report their own recent experience with carotid
      surgery and aneurysm repair in patients aged 80 years or older.

PMID- 9594618
TI  - [Clinical significance of antiphospholipid antibodies].
AB  - Antiphospholipid antibodies (aPL) are a family of autoantibodies with specificity
      for negatively charged phospholipids, or more accurately for their complex to
      phospholipid binding proteins. Their presence is associated with arterial/venous
      thrombosis and recurrent pregnancy loss. These clinical manifestations with the
      persistence of aPL are recognized as antiphospholipid syndrome (APS), one of the
      most common acquired thrombophilia. beta 2-glycoprotein I (beta 2GPI) bears the
      epitope(s) for anticardiolipin antibodies (aCL) on its molecule, and lupus
      anticoagulant activity depends on the presence of beta 2GPI or prothrombin. Thus
      phospholipid binding proteins may have some crucial roles in the pathophysiology
      of thrombotic events in APS.

PMID- 9594620
TI  - [Anti-receptor antibody and autoimmune disease].
AB  - Many receptors are located on the cell surface, and accessible by anti-receptor
      autoantibodies. After binding to the receptor, anti-receptor autoantibodies may
      activate the receptor, mimicking the effect of its genuine ligand, or inhibiting
      activation by ligands. Therefore, anti-receptor autoantibodies have pathogenic
      importance in several autoimmune diseases, such as Graves' disease, myasthenia
      gravis, Type B insulin resistance syndrome, and so on. The measurement of anti
      receptor autoantibodies is often essential in the diagnosis of these diseases.
      There are two kinds of measurement procedures. One measures only binding or
      inhibition of ligand binding to the receptors. That test is simple and available
      in many laboratories, but cannot distinguish the function--stimulation or
      inhibition--of autoantibodies. However, procedures that can measure function are
      rather complicated and may not be available in some laboratories. Not only
      important for diagnosis, anti-receptor autoantibodies can also be utilized to
      study receptor-ligand interactions and receptor activation. Recently, there are
      many studies wherein genetically modified receptors are used for analysis. Here,
      we will present some our results, as examples.

PMID- 9594619
TI  - [Analysis of autoantigens and clinical significance of antinuclear antibodies].
AB  - A highly sensitive RNA-immunoprecipitation assay (Lerner-Steitz assay) is a
      unique and useful method of identifying autoantibodies to RNA-associated
      antigens. In this study, we identified novel autoantibodies to tRNAs using RNA
      immunoprecipitation assay. In screening of 1472 sera by RNA-immunoprecipitation
      using HeLa cell extracts as an antigen source, 41 sera were found to
      immunoprecipitate tRNAs. Fifteen of these 41 sera also immunoprecipitated
      deproteinized tRNAs, indicating that these 15 sera contained anti-tRNA
      antibodies. Three sera immunoprecipitated naked tRNA from E. coli. When in vitro
      transcripts from cDNAs encoding E. coli tRNAs and their synthesized mutants were
      used as antigens, it was demonstrated that the representative serum recognized
      the conformational epitope of the "L"-shape structure which was conserved in all
      tRNAs of all species. This finding suggests the role of bacterial infection in
      the development of autoantibodies and autoimmune diseases. Two of 15 sera
      containing anti-tRNA antibodies were identified as anti-PL-12 (alanyl-tRNA
      synthetase) antibodies. Eleven of the remaining 13 patients were diagnosed as
      either SLE, Sjogren's syndrome or their overlap. In addition, fever, Raynaud's
      phenomenon, polyarthritis, leukocytopenia and characteristic annular erythema
      were frequently found in these patients. Novel autoantibodies to tRNAs appeared
      to be associated with common clinical features but were distinct from previously
      described anti-aminoacyl-tRNA synthetases.

PMID- 9594621
TI  - [The association between autoantibodies to enzyme and diseases--with special
      reference to antibodies to pyruvate dehydrogenase complex (PDH)].
AB  - A serological feature of primary biliary cirrhosis (PBC) is the presence of high
      titer antimitochondrial autoantibodies (AMA) in patient sera. Five different
      target mitochondrial autoantigens recognized by sera from PBC patients have been
      identified as subunits of the 2-oxoacid dehydrogenase complex (2-OADC), of which
      pyruvate dehydrogenase complex-E2 (PDH-E2) is the most prominent antigenic
      component. Extensive molecular and immunological studies in PBC such as cloning
      of mitochondrial autoantigens, mapping of both T and B cell epitopes and
      immunohistochemical studies have provided valuable reagents in the understanding
      of immunopathogenesis of PBC. We mapped the epitope recognized by AMA specific to
      2-oxoglutarate dehydrogenase complex-E2 (OGDC-E2) in patients with PBC using full
      length rat OGDC-E2 cDNA and a series of expression clones spanning the entire
      molecule. It appears that the epitope is dependent on conformation and includes
      the lipoic acid-binding region. Furthermore we have taken advantage of the
      antigenic mapping studies of PDC-E2, OGDC-E2 and branched chain 2-oxoacid
      dehydrogenase complex-E2 (BCOADC-E2) subunits and designed a hybrid clone, pML
      MIT3, that expressed three different immunodominant epitopes. Our results
      indicate that an immunoassay using recombinant, cloned autoantigen is a powerful
      and very specific method for detecting AMA in PBC.

PMID- 9594623
TI  - [GAD antibody in IDDM].
AB  - Glutamic acid decarboxylase (GAD) catalyzes the formation of gamma-aminobutyric
      acid (GABA), which is a major transmitter in the central nervous system. Two
      forms of GAD (GAD65 and GAD67) are known to be expressed in human tissues and
      GAD65 is predominantly expressed in pancreatic beta-cells. Recent findings
      revealed that GAD functions as an autoantigen in human autoimmunity, especially
      in insulin-dependent diabetes mellitus (IDDM). GAD is a key antigen for the
      development of autoimmunity against beta-cells and the production of GADAb
      precedes other autoantibodies such as IAA and ICA512/IA-2Ab prior to the clinical
      onset of IDDM. At onset, GADAb is detected in 50-80% of patients using RIA or RBA
      method. Factors that influence the positivities and titers of GADAb at onset,
      such as onset age, sex, presence of autoimmunity against thyroid, HLA type, have
      been reported. After onset, GADAb titer decreased more slowly than that of
      ICA512/IA-2Ab. These findings suggest that autoantibodies against beta-cells,
      such as GADAb, may develop independently. The presence of GADAb in relatives of
      IDDM patients and NIDDM patients predicts the development of beta-cell
      destruction in combination with other anti-islet autoantibodies.

PMID- 9594622
TI  - [Anti-TPO autoantibodies].
AB  - Thyroid peroxidase (TPO) is a member of the thyroid autoantigens. Anti-thyroid
      autoantibodies, anti-TPO,-thyroglobulin and -TSH receptor autoantibodies, are
      important in diagnosing autoimmune thyroid diseases and for judging treatment
      efficacy. To diagnose chronic thyroiditis, anti-TPO autoantibody detection is the
      most sensitive among the three anti-thyroid autoantibodies. Eighty-five to ninety
      percent of patients with chronic thyroiditis have anti-TPO autoantibodies. Using
      recombinant human TPO protein, a kit measuring anti-TPO antibodies specifically
      have been developed. The developmental process and specificity of the kit are
      discussed. Compared with the microsome test, the most greatest advantage of the
      anti-TPO EIA kit can specifically measure anti-TPO antibodies. Structure of anti
      TPO antibody immunoglobulin, which has been demonstrated over the last several
      years using the phage display method, is also discussed. The most prominent
      feature is that VL is believed to be important in determining anti-TPO antibody
      specificity in contrast to that of other autoantibodies, although VL itself does
      not have TPO-binding activity.

PMID- 9594624
TI  - [Carotid blood flow volume measurement using an ultrasonic Doppler flowmeter-
      predictive diagnosis of ischemic cerebrovascular diseases].
AB  - BACKGROUND: It is difficult to predict ischemic cerebrovascular diseases by
      noninvasive methods before overt symptoms develop. Advanced carotid and cerebral
      atherosclerosis reduce common carotid blood flow volume due to increased
      resistance of peripheral circulation. According to a study in which clinical and
      pathological specimens were compared, the lower threshold for the flow volume in
      normal individuals has been confirmed to be 6.5 ml/s. We investigated the
      possibility that the development of ischemic cerebrovascular diseases can be
      predicted based on blood flow volume. METHOD: We conducted a retrospective study
      on 314 patients who were available for determination of common carotid blood flow
      volume with an ultrasonic quantitative flowmeter. RESULTS: Thirty-three patients
      developed ischemic cerebrovascular attacks during the observation period (onset
      group), while the remaining 281 did not develop attacks (non-onset group). The
      discriminating value for common carotid blood flow volume between the onset and
      non-onset groups was 6.8 ml/s. Based on an odds ratio of 6.7, it was concluded
      that a common carotid blood flow volume of less than 6.8 ml/s is highly likely to
      predict the onset of ischemic cerebrovascular accidents.

PMID- 9594625
TI  - [Diagnosis of myocardial ischemia and viability by 31P nuclear magnetic resonance
      spectroscopy].
AB  - To demonstrate the usefulness of in vivo 31P nuclear magnetic resonance
      spectroscopy (MRS) in the diagnosis of ischemic heart disease, major findings
      from three clinical cardiac MRS investigations performed at our institute are
      summarized. The first study investigated whether 31P MRS with handgrip exercise
      testing could detect myocardial ischemia demonstrated by exercise 201Tl
      scintigraphy. Contrary to findings in normal subjects or patients with fixed
      thallium defects, the ratio of phosphocreatine (PCr) to ATP decreased
      significantly during exercise in patients with reversible thallium defects. In
      the second study, PCr and ATP content was measured by 31P MRS and compared in
      human myocardium with reversible ischemia or scar diagnosed by exercise thallium
      scintigraphy. Although the PCr content decreased in patients with either
      reversible or fixed thallium defects, the ATP content decreased only in the
      latter group. In the third study, postischemic myocardium with chronic mechanical
      dysfunction that exhibits recovery after revascularization in left
      ventriculography was metabolically characterized using quantitative cardiac 31P
      MRS. Postischemic myocardium with reversible mechanical dysfunction demonstrated
      reduced PCr but normal ATP content. These results suggest that 31P MRS is a
      clinically important method both for the detection of myocardial ischemia and in
      the evaluation of myocardial viability.

PMID- 9594627
TI  - [New technology of automated blood cell differential counting].
AB  - Examination of stained peripheral blood films for evaluation of erythrocyte and
      platelet morphology and leukocyte differential count provides considerable data
      for diagnosis of various diseases including hematologic disorders. Since 1980,
      the use of an automated leukocyte differentiation analyzer has become common in
      large clinical laboratories. We surveyed the principles, performance, and
      characteristics of the newest automated leukocyte differential instruments, GEN.S
      system (Coulter), SE-9000/RAM-1 (Toa), CELL-DYN 4000 (Dainabot), ADVIA120 (Bayer
      Sankyo), VEGA RETIC LC-141 (Horiba), and MICROX HEG-120N (Omron). We also
      compared the differentiated function of GEN.S system and CELL-DYN 4000. Automated
      leukocyte differentiation using two instruments correlated well with a reference
      method for leukocyte differential counting proposed by the National Committee for
      Clinical Laboratory Standards (NCCLS) H20-T (eye-count differential). The
      sensitivities of the suspect flag in GEN.S system and CELL-DYN 4000 were 79.3%
      and 83.5%, and the specificities of the two instruments were 100% and 94.9%,
      respectively.

PMID- 9594626
TI  - [Evaluation of cardiac function by biochemical and molecular biological
      techniques].
AB  - We investigated ACE gene polymorphism in 80 patients with hypertrophic
      cardiomyopathy (HCM) and in 88 of their unaffected siblings and children.
      Genotypes were identified by polymerase chain reaction with oligonucleotide in
      intron 16 of the ACE gene. The D allele frequency was higher among patients with
      solitary HCM than among those with familial HCM. We also determined the
      expression of beta-adrenergic receptor kinase (beta ARK) mRNA in the heart in
      patients with congestive heart failure. beta ARK mRNA expression in failing heart
      was significantly increased compared with that in normal heart. These molecular
      biological methods such as investigation of ACE gene polymorphism and beta ARK
      mRNA expression are sufficient for detecting cardiac disease.

PMID- 9594628
TI  - [Simple method for determination of hematopoietic stem cells].
AB  - We investigated on the rapid and easy method for the determination of peripheral
      blood stem cell (PBSC) using the immature information channel (IMI) of the
      automated hematology analyzer (SE-9000). The IMI channel provides information
      regarding immature leukocytes, including blast cells and immature granulocytes.
      CD34 positive cells, which are detected as the CD34 antigen on hematopoietic stem
      cells, were purified from the fractionated peripheral blood stem cell harvesting
      samples using Isolex. These purified CD34 positive cells accumulated in the gate
      corresponding to low Recurrent Frequency values which was presented on IMI
      channel analysis. Thus, the software for the IMI channel analysis to detect only
      the cells accumulated in this gate was developed (HPC program). The peripheral
      blood samples were collected from the subjects (22 cases) before and after
      chemotherapy. Using HPC program, the regression coefficient value between the
      ratio of IMI positive cells and CD34 positive cells in the peripheral blood
      samples was 0.81 (n = 122). As SE-9000 enables to determine the number of PBSC
      easily and rapidly, the measurement of IMI positive cells is clinically useful
      for the monitoring of the rise in PBSC after chemotherapy for mobilization.

PMID- 9594629
TI  - [Leukocyte differentiation by MICRO21 system using neural networking as a type of
      artificial intelligence].
AB  - NeuralVision is a type of artificial intelligence that has the ability to
      identify specific microscopic objects. The MICRO21 system uses neural networking
      to analyze the features of blood cells; color, shape, size, and density, just as
      a technologist would. The basic nucleated blood cell processing procedure of the
      MICRO21 is divided into three general categories; location, segmentation, and
      classification. Classification takes place using the Neural Network and is fine
      tuned during post-processing. We evaluated the performance of the MICRO21
      automated differential vs. manual differential method. The intra-assay of
      leukocyte differentiation by MICRO21 was fairly good in normal samples with
      normal leukocyte counts. The neutrophils, lymphocytes and eosinophils count
      correlated well between MICRO21 and visual count. Post-processing was performed
      after the Neural Network has initially classified the cell, in which the
      confidence levels of MICRO21 to visual count was 87%. By post-processing,
      coincidence ratio of cell-by-cell by MICRO21 and visual count has been improved
      to 97%. Based on the above, MICRO21 is an effective and efficient system for
      locating, storing and displaying images of white blood cells, in which the
      technologist could determine specific characteristics of cells in each
      laboratory. Furthermore, the system may be applied to any blood cell and would be
      important from the perspective of cytological and morphological analysis, such as
      blood cells in bone marrow and body fluid, in the future.

PMID- 9594630
TI  - [Quantitative analysis of multidrug resistance phenotype in hematological
      malignancies].
AB  - Cells with multidrug resistance (MDR) phenotype express P-glycoprotein (P-gp) on
      the cell membrane, which functions as a drug-efflux pump. To quantify the
      expression of the gene encoding P-gp (multidrug resistance 1; MDR1) and assess P
      gp function, we developed competitive reverse transcription-polymerase chain
      reaction (RT-PCR) assay using heterologous competitor RNA and flow cytometric
      analysis using rhodamine 123 (Rh123; an artificial substrate for P-gp),
      respectively. First, we adjusted the assays by analyzing leukemia sublines
      showing various levels of MDR1 expression. The MDR1 expression in leukemia
      sublines quantified by competitive RT-PCR assay showed linearity over a wide
      range, and the results were parallel with those of MDR1 expression measured by
      Northern blot analysis, the P-gp antigen expression measured by flow cytometric
      analysis using MRK16, P-gp function analysis by Rh123 dye-efflux assay, and MDR
      phenotype. Then, we applied these assays to leukemic cells from patients with
      hematological malignancies. All 69 samples from 64 patients were successfully
      assayed, and the range of MDR1 expression was from 1.6 to 100 amol/microgram RNA.
      Since subpopulations of normal lymphocytes show a low degree of P-gp function,
      strict gating of leukemia cells was mandatory for dye-efflux assay of clinical
      samples. MDR1 expression in normal lymphocytes was below 8 amol/microgram RNA. By
      comparison to MDR1 expression quantified by competitive RT-PCR assay with P-gp
      function assessed by Rh123 dye-efflux assay in gated leukemic cells, more than 8
      amol/microgram RNA was regarded as positive MDR1 expression in the leukemic cells
      themselves. These data suggest that these assays are suitable for evaluating P-gp
      expression and function in clinical samples when the proper cut-off value is used
      and may provide insights into the contribution of P-gp to drug resistance in
      hematological malignancies.

PMID- 9594631
TI  - [A case of neuroblastoma with abnormal LD isoenzyme].
AB  - We encountered a patient with neuroblastoma showing remarkably high total LD
      activity (12,585 IU/l). His liver and heart function was normal. In the serum LD
      isoenzyme pattern, LD1 was increased, and LD2 extra band (LD2 ex) was observed on
      the negative pole side of LD2. However, LD2 ex was absent in erythrocytes of the
      patient, which demonstrates the exclusion of genetic factors. Neither the enzyme
      counter current method or immunofixation showed immune complexes, excluding
      anomalies. The LD isoenzyme in a metastatic lymphnode lesion before treatment
      showed increased LD1. The LD isoenzymes in the tissue, removed after 5 courses of
      chemotherapy, showed predominance of LD3 and absence of LD2 ex. Rapid decreases
      in the serum total LD activity and LD1 fraction and the disappearance of LD2 ex
      after chemotherapy suggest that these changes in the two LD fractions are
      associated with production of abnormal LD (LD2 ex) by the tumor.

PMID- 9594632
TI  - [Giant cell tumor (osteoclastoma) of the humerus].

PMID- 9594633
TI  - [Stereotactic convergence irradiation with linear accelerator. Imaging,technique
      and clinical indications].

PMID- 9594634
TI  - [Anxiety immediately before lumbar myelography and possibilities for recognizing
      anxious patients in routine clinical practice].

PMID- 9594635
TI  - [Value of 99mtechnetium-MIBI scintigraphy in breast diagnosis].

PMID- 9594636
TI  - [Bilateral breast carcinoma--a retrospective analysis of 27 patients with a case
      report].

PMID- 9594637
TI  - [Leptomeningeosis leucaemica in acute lymphatic leukemia. A case report].

PMID- 9594638
TI  - [Bilateral renal oncocytoma].

PMID- 9594639
TI  - [An interesting differential diagnosis. Diverticular changes in the small
      intestine].

PMID- 9594641
TI  - [First woman pioneer in radiology].

PMID- 9594640
TI  - [Relation between degenerative changes of the cervical spine and axial mechanical
      weightbearing of heavy loads on the head].

PMID- 9594642
TI  - [Sarcoma botroyoides of the bile ducts].

PMID- 9594643
TI  - Developmental and metabolic adaptations during symbiosis between legume hosts and
      rhizobia.

PMID- 9594644
TI  - Biosynthesis and secretion of rhizobial lipochitin-oligosaccharide signal
      molecules.

PMID- 9594645
TI  - The role of microbial surface polysaccharides in the Rhizobium-legume
      interaction.

PMID- 9594647
TI  - Interaction between Frankia and actinorhizal plants.

PMID- 9594646
TI  - The symbiotic interaction between Azorhizobium caulinodans and Sesbania rostrata
      molecular cross-talk in a beneficial plant-bacterium interaction.

PMID- 9594648
TI  - Strategies to engineer plants resistant to bacterial and fungal diseases.

PMID- 9594649
TI  - Plant-fungal interactions and plant disease.

PMID- 9594650
TI  - Arabidopsis thaliana. A robust model system for studying plant-pathogen
      interactions.

PMID- 9594651
TI  - Engineering resistance against viral diseases in plants.

PMID- 9594652
TI  - Biosynthesis and regulation of coronatine, a non-host-specific phytotoxin
      produced by Pseudomonas syringae.
AB  - Many P. syringae pathovars are known to produce low-molecular-weight, diffusible
      toxins in infected host plants. These phytotoxins reproduce some of the symptoms
      of the relevant bacterial disease and are effective at very low concentrations.
      Phytotoxins generally enhance the virulence of the P. syringae pathovar which
      produces them, but are not required for pathogenesis. Genes encoding phytotoxin
      production have been identified and cloned from several P. syringae pathovars.
      With the exception of coronatine, toxin biosynthetic gene clusters are generally
      chromosomally encoded. In several pathovars, the toxin biosynthetic gene cluster
      also contains a resistance gene which functions to protect the producing strain
      from the biocidal effects of the toxin. In the case of phaseolotoxin, a
      resistance gene (argK) has been utilized to engineer phaseolotoxin-resistant
      tobacco plants. Although P. syringae phytotoxins can induce very similar effects
      in plants (chlorosis and necrosis), their biosynthesis and mode of action can be
      quite different. Knowledge of the biosynthetic pathways to these toxins and the
      cloning of the structural genes for their biosynthesis has relevance to the
      development of new bioactive compounds with altered specificity. For example,
      polyketides constitute a huge family of structurally diverse natural products
      including antibiotics, chemotherapeutic compounds, and antiparasitics. Most of
      the research on polyketide synthesis in bacteria has focused on compounds
      synthesized by Streptomyces or other actinomycetes. It is also important to note
      that it is now possible to utilize a genetic rather than synthetic approach to
      biosynthesize novel polyketides with altered biological properties (Hutchinson
      and Fujii, 1995; Kao et al., 1994; Donadio et al., 1993; Katz and Donadio, 1993).
      Most of the reprogramming or engineering of novel polyketides has been done using
      actinomycete PKSs, but much of this technology could also be applied to
      polyketides synthesized by Pseudomonas when sufficient sequence information is
      available. It is important to note that Pseudomonas produces a variety of
      antimicrobial compounds from the polyketide pathway, including mupirocin
      (pseudomonic acid) (Feline et al., 1977), pyoluteorin (Cuppels et al., 1986), and
      2-4 diacetylphloroglucinol (Phl) (Bangera and Thomashow, 1996). Pseudomonic acid
      is valued for its pharmaceutical properties as an antibiotic (Aldridge, 1992),
      whereas pyoluteorin and Phl have antifungal properties (Howell and Stipanovic,
      1980; Keel et al., 1992). A thorough understanding of the biosynthetic pathway to
      polyketide phytotoxins such as coronatine may ultimately lead to the development
      of novel compounds with altered biological properties. Thus, specific genes in
      the biosynthetic pathways of P. syringae phytotoxins could be deployed in other
      systems to develop new compounds with a wide range of activities.

PMID- 9594653
TI  - DNA transfer from Agrobacterium to plant cells in crown gall tumor disease.

PMID- 9594654
TI  - Import of Agrobacterium tumefaciens virulence proteins and transferred DNA into
      plant cell nuclei.

PMID- 9594655
TI  - Oligosaccharide elicitors in host-pathogen interactions. Generation, perception,
      and signal transduction.

PMID- 9594656
TI  - Holy Tolloido: Tolloid cleaves SOG/Chordin to free DPP/BMPs.

PMID- 9594657
TI  - Groucho: making its Marx as a transcriptional co-repressor.

PMID- 9594658
TI  - Introns-early: slipping lately?

PMID- 9594659
TI  - Structural genomics taking shape.

PMID- 9594660
TI  - Gene therapy--the gutless approach pays off.

PMID- 9594661
TI  - Cancer resistance genes in mice: models for the study of tumour modifiers.
AB  - Smokers have frequently been heard to defend their habit by recounting anecdotes
      about relatives or friends who have smoked heavily for many years without
      developing cancer. While individuals who have survived many years of repeated
      mutagen exposure are probably very rare, their existence suggests that some
      people are intrinsically resistant to the effects of carcinogens, probably
      because of their genetic background. This interpretation is supported by studies
      on mouse strains that are highly resistant to the development of tumours induced
      by treatment with exogenous carcinogens. In this review we discuss the advantages
      of the mouse as a model system for the isolation of cancer-resistance genes that
      have potentially important uses in diagnostics, prevention and tumour therapy.

PMID- 9594662
TI  - Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by
      KSHV.
AB  - A common feature of many tumor viruses is that they possess genes that produce
      specific proteins to inhibit major cellular tumor-suppressor pathways. Despite
      intensive studies, the reasons why these diverse and unrelated viruses have
      independently evolved oncogenes remains obscure. Kaposi-sarcoma-associated
      herpesvirus (KSHV or HHV8) has pirated a number of recognizable cellular genes
      that are key to cell survival and proliferation. In this review, we provide an
      overview of the known activities of these viral genes and show that many of these
      pirated proteins affect the same cellular pathways targeted by other, unrelated
      tumor viruses. We speculate that tumor-suppressor pathways are used by the cell
      as a primary defense against persistent virus infection, in addition to their
      well-known activity in regulating cell proliferation.

PMID- 9594663
TI  - The riddle of MAP kinase signaling specificity.
AB  - Cells encounter an enormous variety of signals in their environments and must
      respond to each stimulus appropriately with changes in their genetic programs.
      Many of these external signals are transduced by a highly conserved eukaryotic
      signaling mechanism, the mitogen-activated protein kinase (MAPK) cascade. How are
      the myriad of inputs transduced accurately so that each evokes a specific
      response? One mechanism would be to have a distinct MAPK cascade for each signal;
      however, the situation appears to be more complicated.

PMID- 9594664
TI  - LIM domains: multiple roles as adapters and functional modifiers in protein
      interactions.
AB  - The LIM domain is a specialized double-zinc finger motif found in a variety of
      proteins, in association with domains of divergent functions or forming proteins
      composed primarily of LIM domains. LIM domains interact specifically with other
      LIM domains and with many different protein domains. LIM domains are thought to
      function as protein interaction modules, mediating specific contacts between
      members of functional complexes and modulating the activity of some of the
      constituent proteins. Nucleic acid binding by LIM domains, while suggested by
      structural considerations, remains an unproven possibility. LIM-domain proteins
      can be nuclear, cytoplasmic, or can shuttle between compartments. Several
      important LIM proteins are associated with the cytoskeleton, having a role in
      adhesion-plaque and actin-microfilament organization. Among nuclear LIM proteins,
      the LIM homeodomain proteins form a major subfamily with important functions in
      cell lineage determination and pattern formation during animal development.

PMID- 9594665
TI  - Exploring protein homology with the Blocks server.

PMID- 9594666
TI  - Dracunculiasis. Global surveillance summary, 1997.

PMID- 9594667
TI  - Where are the Will Pickles of Lautoka, Pegu, Ibadan or Belem?

PMID- 9594668
TI  - Anti-epileptic drug treatment in rural Africa: involving the community.

PMID- 9594669
TI  - Oesophageal transection.

PMID- 9594670
TI  - Epilepsy in practice.
AB  - Epilepsy is a common and often neglected illness in developing countries
      requiring a conscious effort by health workers, especially at community level, to
      enhance access to regular treatment and to motivate patients to continue
      treatment. Effective new drugs have recently come on to the market. However,
      their high cost means that they often cannot be afforded by poor countries.
      Strengthening local and national level organizations may help to motivate health
      workers and the public, improving health services for those with epilepsy and
      preventing serious complications.

PMID- 9594671
TI  - Antiepileptic drug treatment in rural Africa: involving the community.
AB  - The vast majority of patients with epilepsy in developing countries do not
      receive adequate medical treatment and an estimated percentage of 80-90% are
      without any treatment. Poor infrastructure, insufficient availability of drugs
      and scarcity of trained medical personnel are relevant factors for this
      situation. Traditional concepts about epilepsy may also affect acceptance and
      compliance to modern treatment. We report our experience with anti-epileptic drug
      (AED) treatment in a rural African community with a high prevalence of epilepsy.
      After identification of the patients during a prevalence survey on epilepsy, the
      input of the medical service of the district to the treatment scheme was reduced
      to a 6-monthly medical visit to the area and long-term provision of AED to the
      patients. Members of the community were integrated as assistants in the
      distribution of the drugs and community participation was gradually enhanced over
      the first year of the programme. A cost-sharing system for the financing of the
      community assistants was introduced and a self-help committee of epilepsy
      patients and their families was founded. Within the first 20 months the patients
      showed good compliance as indicated by a growing number of patients presenting
      for treatment and a low rate of discontinuation of the treatment. A marked
      improvement could be observed for most of the patients treated with
      phenobarbitone in terms of reduction of seizure frequency although complete
      seizure control was achieved in only a few.

PMID- 9594672
TI  - Voluntary lay supervisors of directly observed therapy for tuberculosis in
      Africa.

PMID- 9594673
TI  - Effectiveness of excision of pre-ulcerative Buruli lesions in field situations in
      a rural district in Ghana.
AB  - The effectiveness of excision of pre-ulcerative Buruli lesions in field
      situations was assessed in a prospective study in an endemic focus in rural
      Ghana. All 50 patients, clinically diagnosed as having pre-ulcerative Buruli
      lesions, had their lesions excised followed by primary suturing. The patients
      were then followed up until the wound healed and thereafter for a year or until
      recurrence. The median duration for complete healing after excision was 31.5 days
      while the 1-year recurrence rate was 16%. None of the patients had any form of
      deformity after healing in contrast with the usual consequences of other forms of
      treatment. Our findings suggest that excision of pre-ulcerative Buruli lesions is
      effective in preventing deformities but less so for preventing recurrence of
      lesion.

PMID- 9594674
TI  - Episiotomy in Burkina Faso.
AB  - Episiotomy is a common obstetric intervention in many countries of the world,
      although little is known about rates in African countries. In recent years, the
      effectiveness of routine episiotomy to prevent severe tears and neonatal asphyxia
      has been questioned, and evidence shows that the procedure results in
      considerable maternal morbidity. This study estimates episiotomy rates in Burkina
      Faso. A high proportion of primigravidae (46%) received an episiotomy when
      trained midwives attended the delivery; a level which indicates the procedure has
      to be regarded as routine practice. The episiotomy rate was lower (26%) in
      primigravidae delivered by auxillary midwives. This proportion is closer to
      recommended selective approaches derived from good research summaries. The tear
      rate in women assisted by midwife and auxiliary staff was similar, suggesting
      that women tear even when the procedure is performed. These results indicate that
      obstetricians and midwives in Burkina Faso should critically appraise whether
      routine episiotomy should be abandoned. The introduction of a labour chart is a
      good vehicle to introduce a policy on avoiding episiotomies.

PMID- 9594675
TI  - Comparison of a rapid dipstick test and thick blood films for detecting parasites
      of plasmodium falciparum used under typical conditions at a semi-rural hospital
      in Cote d'Ivoire.
AB  - This prospective study compares a rapid dipstick test (ParaSight-F) with thick
      blood films for the detection of parasites of P falciparum, under 'typical'
      conditions and constraints to be found in a semi-rural hospital in a tropical
      developing country in Africa. Eighty-two samples were tested using the two
      techniques and found to concur in 95.1% of cases. However, in four of the samples
      the results differed. The thick blood films of 60 samples were later re-read by a
      local reference laboratory. Of these 98.3% were in agreement with the reading
      performed at the hospital. Only one of the 60 slides differed. The rapid dipstick
      test proved to be both easy to use and free from many of the usual constraints
      such as a need for formally trained or experienced laboratory staff, laboratory
      equipment, and reliable water and electricity supplies. In an holoendemic area
      for P falciparum transmission, it would appear to be eminently suitable, in
      technical terms and ease of handling as well as on the basis of rapid results,
      for wider distribution within this region. Its main drawback remains financial.

PMID- 9594676
TI  - Saving more neonates in hospital: an intervention towards a sustainable reduction
      in neonatal mortality in a Nicaraguan hospital.
AB  - A process of change was initiated in a Nicaraguan regional hospital in order to
      achieve a sustainable reduction of early neonatal mortality. A series of
      organizational, educational and hygienic measures was introduced, involving all
      staff in antenatal care, delivery care and neonatal care. Neonatal mortality
      decreased from 56/1000 live births in 1985 to 11/1000 in 1993. A commission of
      maternal and child health, a weekly perinatal audit, the active involvement of
      all staff and dedicated work of key individuals, as well as national policy
      decisions, are considered important determinants of the process. Keeping neonatal
      mortality in focus through continuous analysis of care routines, and through
      external exchange of ideas is important in order to sustain improvements and to
      decrease further the mortality.

PMID- 9594677
TI  - Puerperal sepsis: a preventable post-partum complication.
AB  - Patients with puerperal sepsis following delivery at Ife State Hospital (ISH) of
      Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC) Ile-Ife over a 10
      year period spanning January 1986 to December 1995 were reviewed. One hundred and
      forty-six patients were diagnosed as having puerperal sepsis and there were 8428
      deliveries giving an incidence of 1.7%. The incidence was higher among the
      unbooked patients 71.2%. Predisposing factors were: anaemia in pregnancy, 69.2%;
      prolonged labour (labour lasting up to 12 h or more), 65.7%; frequent vaginal
      examinations in labour (more than five), 50.7%; premature rupture of membranes,
      31.5%; and non-adherence to asepsis during delivery. The case mortality rate was
      4.1%. Antenatal care and supervised hospital delivery should be encouraged in
      order to prevent or reduce this serious post-partum morbidity.

PMID- 9594678
TI  - Treatment of malnutrition in Brazil: simple solutions to common problems.
AB  - At the largest rehabilitation centre in Ceara, Brazil, the World Health
      Organization (WHO) guidelines for improved dietary management of severe
      malnutrition were implemented. Rates of weight gain increased fourfold, daily
      food costs were reduced, and staff time was saved. Implementation was achieved
      within 1 week, including training. Other centres are encouraged to adopt similar
      measures.

PMID- 9594679
TI  - Phenol injection for benign prostatic hypertrophy.

PMID- 9594680
TI  - Improvised method for adequate lubrication and anaesthesia of the urethra.

PMID- 9594681
TI  - Partial oesophageal transection: an alternative surgical method for bleeding
      oesophageal varices.

PMID- 9594682
TI  - Appropriate technology in transportation of sick newborns in developing
      countries.

PMID- 9594683
TI  - Is vitamin B6 supplementation of isoniazid therapy useful in childhood
      tuberculosis.
AB  - We present the results of a prospective single blind placebo controlled study
      performed to establish whether vitamin B6 supplementation of isoniazid therapy is
      useful in childhood tuberculosis. Eighty-five children suffering from
      tuberculosis (TB) and admitted between 1 October 1993 and 31 March 1995 to the
      Hospital of IME-Kimpese (Lower Zaire) were included. All were treated with
      isoniazid and other antitubercular drugs and were randomized to receive either
      vitamin B6 supplementation or placebo. No case of neurological or
      neuropsychiatric disorder was observed in the two groups during the 6 months of
      the treatment and 3 months after the treatment. These results suggest that the
      vitamin B6 supplementation of isoniazid therapy is unnecessary in childhood TB.

PMID- 9594684
TI  - The role of traditional birth attendants in a safe delivery programme in
      Bangladesh.

PMID- 9594685
TI  - Drug resistant enterococci in a south Indian hospital.

PMID- 9594686
TI  - A familial case of fibrodysplasia ossificans progressiva (myositis ossificans
      progressiva).

PMID- 9594687
TI  - Rhinosporidiosis in the nasal cavity.
AB  - A case of nasal rhinosporidiosis in a 17-year-old patient from the Middle Belt
      area of Nigeria is described, the first such case seen in 16 years since this
      centre was established. The clinical features and the results of gross and
      microscopic examination of biopsy material are presented.

PMID- 9594688
TI  - An infected primary retroperitoneal cyst.

PMID- 9594689
TI  - Giant cervical polyp.

PMID- 9594690
TI  - Radial club hand with a short hypoplastic radius treated surgically.

PMID- 9594691
TI  - Rib tuberculosis simulating Tietze's syndrome.

PMID- 9594692
TI  - Sonographic diagnosis of intestinal ascariasis.

PMID- 9594694
TI  - Screening for syphilis in pregnant women.

PMID- 9594693
TI  - Neonatal tuberculosis of the spine.

PMID- 9594696
TI  - Peau d'orange of the breast--not always a sign of advanced breast cancer.

PMID- 9594695
TI  - The latent phase: no obstacle for the use of partograms.

PMID- 9594697
TI  - Tobacco control through Imams.

PMID- 9594699
TI  - Prepucial Epstein pearl revisited.

PMID- 9594698
TI  - Catheter-needle device in operative management of hydatid disease of the liver.

PMID- 9594701
TI  - Access to care.

PMID- 9594700
TI  - Low reticulocyte count in severe cases of anaemia.

PMID- 9594702
TI  - Managing TMD.

PMID- 9594703
TI  - The facts on oral cancer.

PMID- 9594704
TI  - Forensic dentistry. "It is gruesome, but it must be done".

PMID- 9594705
TI  - Dental provider contracts--most favored nation clauses.

PMID- 9594706
TI  - The successful dentist.

PMID- 9594707
TI  - Why can't we be friends?

PMID- 9594708
TI  - The business of dentistry. Financial experts look at the future of the dental
      industry.
AB  - A financial conference, held in February, took a look at where the dental
      industry is heading. Given the consolidations already apparent in the
      manufacturing and laboratory aspects of the profession and the growth of managed
      care companies, what does the future hold for the profession?

PMID- 9594709
TI  - Does CDS have an open election? Chicago Dental Society.
AB  - The Chicago Dental Society's unique system of electing officers has survived
      since the 1940s. Does the coalition system still serve the needs of a changing
      professional organization or has the time come for the Chicago Dental Society to
      explore other, more traditional, methods of electing its officers?

PMID- 9594710
TI  - Minimize your legal liability.

PMID- 9594711
TI  - Fabricating radiographic stents in implant treatment planning.
AB  - This article provides a step-by-step procedure for producing radiographic stents.
      Two common treatment scenarios are explored.

PMID- 9594712
TI  - Battling bad breath: a new approach to an old problem.
AB  - Bad breath plagues millions of people in the US. Because breath malodor is viewed
      as a social, not medical, condition, bad breath usually is not part of dental
      school curriculums. Desperate halitosis sufferers looking for help are turning to
      the dental profession for answers.

PMID- 9594713
TI  - CDS 1996 survey: Chicago area dentists profiled.
AB  - The CDS Communications Department commissioned a survey of 1,500 Chicago-area
      dentists to determine who they are and what they think. Issues such as parents'
      attitudes about their children's oral care and senior citizens' abilities to
      maintain dental health are explored and practitioner demographics are presented.

PMID- 9594714
TI  - Dental assistants make a difference. Examinations offered at Midwinter Meeting.
AB  - A well-trained, credentialed dental assistant is an asset to any dental practice.
      Two important examinations will be held at this year's Midwinter Meeting to
      ensure that your dental assistant continues to be a valuable part of your dental
      team and a source of information for your patients.

PMID- 9594715
TI  - Nonmembership matters.

PMID- 9594716
TI  - ACDS: helping to heal. Interview by Laura Fulton.

PMID- 9594717
TI  - Between friends.

PMID- 9594718
TI  - The false signs of child abuse.

PMID- 9594719
TI  - Germ warfare.

PMID- 9594721
TI  - To Russia with love.

PMID- 9594720
TI  - Capitol concerns.

PMID- 9594722
TI  - HIV-employment issues.

PMID- 9594723
TI  - The Indian Health Service needs you.

PMID- 9594724
TI  - Managed care in our own practice.

PMID- 9594725
TI  - Staying healthy in the dental office.

PMID- 9594726
TI  - The true cost of dentistry.

PMID- 9594728
TI  - Use care when writing letters of reference.

PMID- 9594727
TI  - Treatment of the patient receiving Coumadin anticoagulant therapy.
AB  - Minimizing the risk of bleeding as well as the risk of thromboembolism in dental
      patients being treated with anticoagulants is a common challenge for
      practitioners. This article features tips on evaluating and managing these
      patients.

PMID- 9594730
TI  - A new specialty of prosthodontics.

PMID- 9594729
TI  - Simple IRAs--exactly what are the costs?

PMID- 9594731
TI  - Case report: infra-occluded deciduous molars: a review and alternative treatment
      approach.
AB  - A review of the literature regarding the prevalence, aetiology, clinical features
      and management of infra-occluded deciduous molars is presented. There is no
      general agreement as to the treatment of infra-occluded deciduous molars but
      extraction therapy is strongly recommended in the literature. The complications
      of nontreatment are discussed and an alternative treatment approach is presented.

PMID- 9594732
TI  - A comparison of two methods for recording the retruded jaw relation in edentulous
      subjects.
AB  - The purpose of this study on 19 edentulous patients was to compare the retruded
      jaw relations recorded on wax rims at the registration stage with those recorded
      on finished dentures at insertion. An intra-oral centre-point trace served as the
      reference point for both sets of measurements. Results showed the two techniques
      to give mean retruded positions 0.25 mm apart in the occlusal-sagittal plane, but
      the distributions of the two sets of results differed; those recorded on finished
      dentures had greater precision, with smaller range and standard deviation. The
      work confirms the usefulness of a post insertion check record carried out on
      complete dentures to minimise any occlusal errors introduced at the registration
      stage.

PMID- 9594733
TI  - Case report: multi-disciplinary treatment in the management of traumatised
      anterior teeth.
AB  - A case is described in which delayed treatment of traumatised anterior teeth
      resulted in unwanted tooth movement. Loss of interocclusal space and a reduction
      in clinical crown height complicated restoration of the teeth. Treatment using
      fixed-appliances and protraction headgear followed by surgical crown-lengthening
      facilitated the restorative process.

PMID- 9594734
TI  - Fissure caries diagnosis and resulting treatment decisions by clinical community
      dental officers and general dental practitioners.
AB  - In this in vitro study, 12 General Dental Practitioners and 13 Clinical Community
      Dental Officers examined the occlusal, buccal and palatal pits and fissures of 35
      extracted molar teeth. They were asked to make a management/treatment decision,
      on the basis of their diagnosis of caries, whether each tooth should be left
      untreated, fissure sealed or investigated. After all the management/treatment
      decisions had been made, the teeth were serially sectioned perpendicular to the
      occlusal surface and examined for the presence of caries in dentine. It was
      impossible to demonstrate differences in the management/treatment decisions and
      the diagnosis of caries made by the two groups. No significant difference in
      sensitivity or specificity could be detected between operators diagnosing by
      visual inspection alone and those using visual inspection in combination with a
      tactile method. The use of radiographs did not significantly improve the validity
      of the diagnosis or management of fissure caries.

PMID- 9594735
TI  - Laminate veneer provisionalisation.
AB  - The advantages of provisional laminate veneers are described. Provisional
      coverage is justified both from the aesthetic and functional viewpoints. Both
      direct and indirect methods for fabricating provisional laminate veneers are
      outlined. Among the direct methods for Laminate Veneer fabrication, the use of
      the preoperative impression, preformed polycarbonate crowns, and vacuform matrix
      are presented. These methods are quick, fabrication is easy, and the results are
      highly aesthetic with good patient comfort and satisfaction.

PMID- 9594736
TI  - Influence of tissue conditioning materials upon the crystalline structure of
      dental stone and improved dental stone.
AB  - Dental stone and improved dental stone were crystallised in contact with six
      commercial tissue conditioning materials. Their influence on the crystalline
      structure of dental stone and improved dental stone were investigated using a
      scanning electron microscope. Tissue conditioning materials cause horizontal
      orientation of the crystals of calcium sulphate CaSO4 2H2O dihydrate.

PMID- 9594737
TI  - The effect of surface treated UHMWPE beads on some properties of acrylic resin
      denture base material.
AB  - UHMWPE in the form of experimental surface treated beads was added to acrylic
      resin denture base material in various percentages to form a composite material.
      The influence on doughing and manipulation times, and transverse and impact
      strength was examined. The results indicated that the manipulation times, were
      not significantly affected as the percentage of UHMWPE beads in the acrylic resin
      powder increased. Increasing the percentage of incorporated UHMWPE beads resulted
      in an inconsistent decrease in the modulus of rupture and no effect on the impact
      fracture resistance. It was concluded that the use of treated UHMWPE beads is of
      no significant benefit to the properties of acrylic resin.

PMID- 9594738
TI  - Factors influencing the radiographic appearance of bony lesions.

PMID- 9594739
TI  - Effects of cleaning, chemical disinfection, and sterilization procedures on the
      mechanical properties of endodontic instruments.
AB  - The aim of this study was to test and compare the values of torsional moment,
      torsional angular deflection, bending moment, and permanent angular deflection of
      three designs of root canal files (Unifile, Flexofile, and H-File) before and
      after cross-infection treatment procedures, according to ANSI/ADA specification
      no. 28. An increase in value for all mechanical properties tested was observed
      after the treatment procedures, with the exception of Flexofile wherein a
      decrease in permanent angular deflection was evident. Unifile showed a decrease
      in torsional moment and bending moment. The changes in mechanical properties
      after treatment procedures ranged from 0.1 to 63% from the control groups.
      Generally, the changes in values observed were insignificant and still well
      within ANSI/ADA specification no. 28. Thus, they do not have any clinical
      significance.

PMID- 9594740
TI  - Excisional wound healing following the use of IRM as a root-end filling material.
AB  - Intermediate Restorative Material (IRM) has been advocated as a root-end filling
      material based primarily on reports of clinical success and various leakage
      studies. The objectives of this study were to determine the excisional wound
      healing responses of the periradicular tissues to IRM root-end filling material
      and to compare this with the wound healing responses to amalgam and orthograde
      gutta-percha root-end filling materials. Mandibular premolars in dogs were
      obturated, root-ends resected, and the healing responses associated with root-end
      fillings of IRM, amalgam, and orthograde gutta-percha were evaluated
      microscopically and radiographically at postsurgical intervals of 10 and 45 days.
      The excisional wound healing responses associated with IRM root-end fillings were
      normal at both postsurgical intervals. There was no evidence of inhibition of
      dentoalveolar or osseous wound healing associated with IRM, amalgam, or
      orthograde gutta-percha. Statistical analysis showed no difference in wound
      healing between the 3 root-end filling materials.

PMID- 9594741
TI  - In vitro evaluation of the antibacterial effects of intracanal micro plasma
      system treatment.
AB  - Forty freshly extracted single-rooted teeth were prepared to a size 25 master
      apical file, autoclaved, and inoculated with a known quantity of Actinomyces
      naeslundii. The teeth were divided into four groups (n = 10), including an
      untreated control group. The three treatment groups were exposed to Micro Plasma
      System (MPS), 0.5% NaOCl and 0.5% NaOCl + MPS respectively. The content of each
      root canal was absorbed by sterile paper points, diluted in 2 ml Schaedler Broth
      Medium, and incubated on blood agar. The number of CFU was determined. Data
      analysis, using an analysis of variance and Scheffe's test at the 1% level
      (Statview II software), indicated a significant reduction in CFU count for the
      three treatment groups compared to the control group. For the three treatment
      groups, no significant intergroup differences were observed.

PMID- 9594742
TI  - Cleaning of endodontic files, Part I: The effect of bioburden on the
      sterilization of endodontic files.
AB  - Ninety-two new endodontic files were randomly assigned to five groups with
      varying parameters of contamination, cleaning method, and sterilization (steam or
      chemical). Files were instrumented in bovine teeth to accumulate debris and a
      known contaminant, Bacillus stearothermophilus. Positive controls produced growth
      on both T-soy agar plates and in T-soy broth. Negative controls and experimental
      files (some with heavy debris) failed to produce growth. The results showed that
      there was no significant difference between contaminated files that were not
      cleaned before sterilization and contaminated files that were cleaned before
      sterilization. Bioburden present on endodontic files does not appear to affect
      the sterilization process.

PMID- 9594743
TI  - An in vitro evaluation of coronal microleakage in obturated root canals without
      coronal restorations.
AB  - A study was conducted to evaluate coronal microleakage of Super EBA and Ketac
      Endo when used as sealers with single-cone gutta-percha (GP) root canal
      obturation. The root canals of 24 extracted human teeth were instrumented with
      flared preparations to a minimum #40 master apical file size. Ten teeth were
      obturated with a single GP cone and Super EBA as the sealer and ten teeth were
      obturated with a single GP cone and Ketac-Endo as the sealer. Four teeth were
      used as controls. Salivary bacterial microleakage studies were conducted to
      determine whether these sealers could prevent coronal microleakage through the
      root canal in the absence of a coronal tooth restoration. There was no bacterial
      penetration through the apical foramen for either sealer tested during the 60-day
      test period.

PMID- 9594744
TI  - Stimulation of interleukin-1 beta production of human dental pulp cells by
      Porphyromonas endodontalis lipopolysaccharide.
AB  - IL-1 beta is synthesized as an inactive precursor, which is subsequently
      processed by IL-1 beta converting enzyme (ICE) and found extracellularly as a
      mature biologically active polypeptide. Also, IL-1 beta has been detected in
      necrotic and inflamed dental pulp. We examined the IL-1 beta production in human
      dental pulp (HDP) cells treated with lipopolysaccharide (LPS) from Porphyromonas
      endodontalis (P. e.) isolated from root canals and radicular cyst fluids. We
      demonstrated that P. e. LPS stimulated IL-1 beta release from HDP cells in a time
      and dose-dependent manner. However, ICE activity was not increased by P. e. LPS.
      Northern blot hybridization analysis revealed that the IL-1 beta mRNA level in
      HDP cells was increased by P. e. LPS. These results suggest that stimulation of
      IL-1 beta release from HDP cells by P. e. LPS may have an important role in the
      progression of inflammation in pulpal and periapical disease.

PMID- 9594745
TI  - Interaction of calcium hydroxide with zinc oxide-eugenol type sealers: a
      potential clinical problem.
AB  - When a ZnOE type sealer was placed in root canals treated previously with calcium
      hydroxide dressing, an accelerated sealer setting rate occasionally occurred.
      This clinical observation led to the present experimental design aiming to
      investigate the effect of calcium hydroxide on a ZnOE cement and ZnOE type
      sealers and to preliminarily assess the removal efficiency of a calcium hydroxide
      preparation from root canal systems. Micro-MIR FTIR spectroscopy was used to
      quantify the effect of calcium hydroxide on the setting reactions of a ZnOE
      cement and two ZnOE type sealers. The removal efficiency of calcium hydroxide
      from root canal systems was evaluated after treatment with NaOCl; NaOCl and
      filing; and NaOCl plus EDTA and filing. Calcium hydroxide preferentially
      interacted with eugenol inhibiting the ZnO-eugenol chelate formation. The Ca(OH)2
      eugenol interaction was rapid, and kinetically dependent, leading to residual
      eugenol in the set product. The set ZnOE cement and the ZnOE type sealers in
      contact with calcium hydroxide were brittle in consistency and granular in
      structure. Although none of the treatments tested completely removed calcium
      hydroxide from root canals, treatment with EDTA significantly reduced the extent
      of residual calcium hydroxide.

PMID- 9594746
TI  - Spatial reproduction of the root canal system by magnetic resonance microscopy.
AB  - This study was intended to achieve an accurate spatial reproduction of the root
      canal system of extracted teeth by magnetic resonance microscopy (MRM). The
      measurements were performed in a Bruker spectrometer AMX 300 WB (300 MHz, 7T)
      with microimaging attachment. The data processing was carried out by a 3D-Fourier
      analysis and reconstructions were done by the UXNMR (Bruker) software system. The
      voxel resolution isotropically reached 98 microns, so that insights into the
      interior of teeth on a microscopic level could be obtained. The spatial
      configuration of the root canal system could be depicted in all parts from crown
      pulp to even small lateral canals. Within the pulp, tissue differences in its
      tissue texture were ascertained. As the necessary strong magnetic fields
      presently are not allowed to be used in people and as the acquisition of data is
      costly, the noninvasive MRM technique presently can be applied only in
      nonclinical situations.

PMID- 9594747
TI  - Pulpal lesions in normal and cyclosporin A treated rats.
AB  - The objective of this study was to examine the development of pulpal lesions in
      the lower molar of control and cyclosporin A (CyA) treated rats. The pulps of the
      first lower molars of 20 normal and 20 CyA treated rats were exposed and left
      open into the oral cavity. Five animals of each group were killed at 7, 14, 21,
      and 28 days after the pulp exposure. The specimens were sectioned sagittally at a
      thickness of 7 microns and stained with hematoxylin and eosin. The pulpal lesions
      were similar for both normal and CyA treated rats in all studied periods and the
      differences between both groups were not statistically significant by the Student
      t test at the 5% (0.05) level of significance, indicating that the
      immunosuppression did not alter the evolution of the inflammatory process.

PMID- 9594748
TI  - Removal of Thermafil root canal filling material.
AB  - The aim of this study was to evaluate if removal of Thermafil plastic carriers
      and reestablishment of working length were possible in single rooted teeth filled
      with the Thermafil system. Twenty freshly extracted maxillary central incisors
      were prepared and filled with #30 Thermafil plastic obturators according to
      manufacturer's recommendations. Teeth were divided in two groups: Group I: 10
      teeth were retreated using dimethylformamide as a solvent. Group II: 10 teeth
      were retreated using chloroform as a solvent. Removal of filling material was
      performed manually using K files and H files alternately between carrier and
      dentinal walls. The average time needed to remove the plastic carrier was 7 min
      for group I and approximately 6 1/2 min for group II. No deformation of the
      plastic carrier was observed after removal from the canal. Removal of plastic
      carriers and measurement of the proper working length were easily performed using
      manual endodontic instruments. Chloroform greatly enhanced this procedure.

PMID- 9594749
TI  - Preeruptive idiopathic coronal resorption: a case report.
AB  - A bitewing radiograph obtained from a general dentist revealed an intracoronal
      radiolucency within an unerupted immature permanent second molar. This rare
      entity was successfully treated by surgical exposure and vital pulp therapy.
      Apexogenesis was confirmed radiographically and a permanent restoration placed at
      the time of eruption. Possible etiologies for this condition are discussed and
      recommendations for treatment are proposed.

PMID- 9594750
TI  - Mandibular molar with 5 canals: report of a case.
AB  - A unique case of a mandibular molar with 5 canals is described. Literature
      pertaining to the analysis of the morphology of mandibular first molars is
      reviewed. Clinicians should thoroughly examine the pulpal floor and radiographs
      for the possibility of additional canals.

PMID- 9594751
TI  - Properties of endodontic hand instruments used in rotary motion. Part 3.
      Resistance to bending and fracture.
AB  - Bending and torsional properties of 24 different types of nickel-titanium K
      files, titanium-aluminium K-files and reamers, conventional stainless steel K
      files and reamers, and flexible stainless steel instruments were investigated
      corresponding to ISO 3630-1 by determination of the bending moment on the one
      hand and the torque and angular deflection on the other. Numbers 15, 25, and 35
      instruments were tested with a sample size of 10 instruments for each type and
      size. In ascending order of bending moment the instruments ranked: nickel
      titanium K-files, titanium-aluminium K-files and reamers, flexible stainless
      steel instruments, conventional stainless steel K-files, and reamers. Nickel
      titanium, titanium aluminium, and flexible stainless steel instruments displayed
      lower torque values than conventional stainless steel K-files and reamers. The
      average angular deflection ranged from 380 degrees (#15 reamer) to 2370 degrees
      (#35 K-file). Overall, the fracture risk of the instruments tested in this study
      was comparably low.

PMID- 9594752
TI  - Influence of the removal of coronal gutta-percha on the seal of root canal
      obturations.
AB  - The purpose of this study was to compare the quality of the coronal seal of
      lateral and vertical condensations after removal of the coronal gutta-percha with
      two different techniques. One hundred single-rooted human teeth with one root
      canal were used. After cleaning and shaping, the teeth were divided into 4 equal
      groups. In groups 1, 3 and 2, 4 vertical and lateral condensations were performed
      respectively. Then, the coronal portion of gutta-percha was removed with heat
      carriers alone for groups 1 and 2 and with heat-carriers and compaction for
      groups 3 and 4. Apical microleakage was determined using pressurized fluid
      filtration measured at different time intervals up to 24 wk. The results showed
      that the alternation of heat-carriers and compaction enhances the quality of the
      coronal seal. The obturation with the vertical condensation technique resulted in
      a better seal independently of the gutta-percha removal technique.

PMID- 9594753
TI  - A new single-step technique for apical retrofilling that significantly reduces
      microleakage.
AB  - One of the properties of an ideal retrofilling material is little or no
      microleakage. A new dentin bonding agent based on polyacrylic acid (PAA) is
      ideally suited to the moist apical environment because of its hydrophilic nature.
      PAA as a dentin bonding agent for apical retrofillings was tested in an in vivo
      leakage study using single canal roots of extracted human teeth. Bonding was
      attained by pretreatment of the dentin in apical retrofilling preparations with a
      solution of PAA, followed by placement of a nonaqueous restorative material.
      Using PAA as dentin bonding agent reduced apical leakage at statistically
      significant levels with Super EBA as a restorative material. In vivo testing is
      required to validate these findings.

PMID- 9594754
TI  - Immunohistochemical study of gamma-aminobutyric acid and bombesin/gastrin
      releasing peptide in human dental pulp.
AB  - This study investigated the presence of the putative peripheral neuromodulators
      Gamma-aminobutyric Acid (GABA) and Bombesin/Gastrin-Releasing Peptide (BN/GRP) in
      the human tooth pulp. Caries free and asymptomatic carious teeth were processed
      for paraffin embedding and sectioned at six microns. From each specimen, sections
      were stained with hematoxylin and eosin; other sections were subjected to Avidin
      Biotin-Peroxidase Complex immunohistochemistry for GABA and BN/GRP. Sections of
      rat brain and small cell lung carcinoma served as positive controls. Results
      indicate the presence of specific GABA-like and BN/GRP-like immunoreactivity
      within the pulps of both normal and carious teeth. Overall staining for both
      ligands was significantly more intense within inflamed pulps. Based on their
      actions elsewhere, GABA and BN/GRP may play a role in the dental pulp as
      peripheral neuromodulators or as growth factors.

PMID- 9594755
TI  - Effect of agents used in perforation repair on osteoblastic cells.
AB  - The effects of dental materials on osteoblastic responses in bone were measured
      using biosynthesis of matrix proteins, osteopontin (OPN), and osteocalcin (OCN)
      as indices. Materials used in perforation repair were standardly mixed and
      extracted in sterile water for 10 days. Extracts were added to the medium of
      osteoblastic ROS 17/2.8 cells and cultured for 48 h. Water incubated in parallel
      served as the vehicle/dilution control. 1,25-Dihydroxyvitamin D3, which increases
      biosynthesis of OPN and OCN, served as the positive control. After culture, total
      cellular RNA was isolated from individual monolayers, and Northern blotting was
      performed to quantitate mRNA levels encoding OCN and OPN. mRNA levels in treated
      samples were compared with controls, and significant differences were detected
      for several materials. Changes in matrix biosynthesis were modest (< 2-fold),
      compared with 1,25-dihydroxyvitamin D3 (6-fold). Materials used in perforation
      repair may produce small, but measurable effects on osteoblastic responses.

PMID- 9594756
TI  - Histopathological study of a newly developed root canal sealer containing
      tetracalcium-dicalcium phosphates and 1.0% chondroitin sulfate.
AB  - We studied the possibility of the clinical use of a calcium phosphate-type newly
      developed sealer composed of tetracalcium phosphate, dicalcium phosphate
      dihydrate, and a modified McIlvain's buffer solution (TDM). Another sealer using
      the buffer solution, to which 2.5% chondroitin sulfate was added to promote wound
      healing (TDM-S), was also studied. TDM and TDM-S were histopathologically
      compared with another type of calcium phosphate sealer (ARS), which is
      commercially available in Japan, in the dorsal subcutaneous tissue and in the
      periapical tissue of rats. TDM and TDM-S caused no inflammatory reactions in the
      subcutaneous tissue. The periapical tissue reacted mildly to them. ARS caused
      severe inflammatory reactions in both the subcutaneous and the periapical tissue.
      These results indicate that TDM-S has excellent histocompatibility and potential
      as a root canal sealer.

PMID- 9594757
TI  - Intracanal medicaments: evaluation of the antibacterial effects of chlorhexidine,
      metronidazole, and calcium hydroxide associated with three vehicles.
AB  - The use of an intracanal medicament may be helpful in eliminating remaining
      bacteria that survived inside root canals after complete chemomechanical
      preparation. This study evaluated the antibacterial activities of medicaments
      that act by means of contact, and not by vapor release, against obligate and
      facultative anaerobic bacteria commonly found in endodontic infections. The
      medicaments used were 0.12% chlorhexidine gel; 10% metronidazole gel; calcium
      hydroxide plus distilled water, calcium hydroxide plus camphorated
      paramonochlorophenol (CPMC); and calcium hydroxide plus glycerin. An agar
      diffusion test was used, and the zones of bacterial inhibition around each
      medicament were recorded and compared. The results revealed that calcium
      hydroxide/CPMC paste was effective against all bacterial strains tested.
      Chlorhexidine was also inhibitory to all strains. It was about as effective as
      calcium hydroxide/CPMC paste against most of the strains. Metronidazole also
      caused inhibition of growth of all obligate anaerobes tested and was more
      effective than calcium hydroxide/CPMC against two strains. Calcium hydroxide
      mixed with distilled water or glycerin failed to show zones of bacterial
      inhibition, probably because of limitations of the agar diffusion test.

PMID- 9594758
TI  - Canal wall planning by engine-driven nickel-titanium instruments, compared with
      stainless-steel hand instrumentation.
AB  - Twenty-two mesial roots of extracted human mandibular molars were divided into
      two groups based on root curvature and length. The mesiolingual canals were
      instrumented using either Flexofiles in a step-back anticurvature filing method,
      or they were instrumented with engine-driven 0.02 taper nickel-titanium files.
      Ground sections were prepared at 1-, 2.5-, and 5-mm levels from the working
      length. The mesiobuccal canal was used as an uninstrumented control for predentin
      character. Digitizing software was used to calculate the instrumented portion as
      a percentage of the total canal perimeter. The results indicated no significant
      difference in overall canal wall planning between the two groups and no
      significant difference at each of the three levels.

PMID- 9594759
TI  - Linear dye penetration of a calcium phosphate cement apical barrier.
AB  - Linear dye penetration was evaluated in teeth with open apices in which calcium
      phosphate cement was used as an apical barrier to facilitate obturation. The
      apical foramens of 42 extracted single-rooted human teeth were opened to a size
      90 file. Half the teeth received apical barriers consisting of calcium phosphate
      cement (CPC) followed by obturation using a customized gutta-percha cone/ lateral
      condensation technique. The other half were obturated without benefit of apical
      barriers. Linear dye penetration was measured after 48 h exposure to India ink.
      The teeth receiving apical CPC barriers before obturation had significantly less
      dye penetration than teeth without apical barriers. Based on its proven
      biocompatibility and osteconductive potential, calcium phosphate cement may serve
      well as a replacement for calcium hydroxide in a single-visit immediate apical
      barrier apexification technique.

PMID- 9594760
TI  - An evaluation of 2% lidocaine with different concentrations of epinephrine for
      inferior alveolar nerve block.
AB  - The purpose of this study was to compare the degree of anesthesia obtained with
      2% lidocaine with three different concentrations of epinephrine for inferior
      alveolar nerve block. Using a repeated measures design, 30 subjects randomly
      received an inferior alveolar injection using masked cartridges of each solution
      at three successive appointments. The first molar, first premolar, lateral
      incisor, and contralateral canine (control) were blindly tested with an Analytic
      Technology pulp tester at 3-min cycles for 50 min. No statistically significant
      differences in success and failure were found among the 1:50,000, 1:80,000, and
      1:100,000 concentrations of epinephrine.

PMID- 9594762
TI  - Three root canals and dens formation in a maxillary lateral incisor: a case
      report.
AB  - A 19-yr-old female presented with three root canals and dens formation in a
      maxillary right lateral incisor. This rare condition was treated with
      conventional endodontic therapy.

PMID- 9594761
TI  - Comparison of triazolam, diazepam, and placebo as outpatient oral premedication
      for endodontic patients.
AB  - Triazolam and diazepam were compared as oral antianxiety agents in a randomized
      double-blind, placebo-controlled clinical study of 79 endodontic patients with
      elevated anxiety regarding endodontic treatment. Patients who scored > or = 10 on
      the Corah Dental Anxiety Survey received oral formulations of triazolam (0.25
      mg), diazepam (5 mg), or placebo. Before, during, and after the endodontic
      procedure, patients completed psychomotor tests and anxiety scales, and were
      evaluated for 24-h postoperative recall. In comparison with diazepam and placebo,
      triazolam was significantly better for decreased anxiety (p < 0.05), impaired
      cognitive function (p < 0.05), patients' rating of drug effectiveness (p < 0.05),
      and amnesia to clinical events (p < 0.02) and pictures (p < 0.03). Diazepam
      showed similar trends compared with placebo, but to a lesser degree. Diazepam
      also had a much longer recovery period. No adverse effects were noted with either
      drug. These findings suggest that orally administered triazolam (0.25 mg) is a
      safe and more effective anxiolytic agent than diazepam (5.0 mg) for endodontic
      patients.

PMID- 9594763
TI  - Mandibular premolar with two roots.

PMID- 9594764
TI  - Identification of bradykinin, substance P, and neurokinin A in human dental pulp.
AB  - Methodology was developed that uses reverse phase, high performance liquid
      chromatography (HPLC) to identify and quantify bradykinin, substance P, and
      neurokinin A contained in dental pulp tissue. Pulp tissue was prepared and
      homogenized from teeth frozen in liquid nitrogen, Known amounts of three
      substances found in inflamed tissue were added to the homogenized tissue and also
      to bovine serum albumin (BSA) (positive control), and supernatants were analyzed
      using HPLC. Other pulp tissue was prepared and analyzed without the addition of
      the substances. Recovery from the pulp and BSA with added substances was similar,
      with bradykinin recovered maximally. In pulp tissue without additions, all three
      substances were recovered. Thus HPLC appears to be a viable alternative to other
      methods for identification of these substances and allows for their
      quantification.

PMID- 9594765
TI  - EDTA inhibits in vitro substrate adherence capacity of macrophages: endodontic
      implications.
AB  - The disodium salt of ethylenediamine tetraacetate (EDTA) is a calcium ion
      chelator used in endodontics to enlarge root canals. This study investigated the
      effect of EDTA on substrate adherence capacity of rat inflammatory macrophages to
      determine if EDTA leakage to periapical tissues during root canal therapy can
      alter macrophage function. Inflammatory macrophages were obtained from Wistar
      rats and resuspended in RPMI-1640 medium. Substrate adherence capacity assays
      were carried out in Eppendorf tubes for 15 min of incubation at 37 degrees C in a
      humidified atmosphere of 5% CO2. The adherence index (AI) was calculated. Results
      showed that EDTA decreased substrate adherence capacity of inflammatory
      macrophages in a time and dose-dependent manner. The lowest EDTA concentration
      that caused a significant inhibition of AI was 50 mM (p < 0.05), and the EDTA
      concentration that caused half-maximal inhibition (IC50) was 194 +/- 20 mM (p <
      0.01). Calcium chloride (10 mM) increased the adherence index of macrophages by
      17.1% (p < 0.05) and decreased the EDTA inhibitory effect on AI by 49.5% (p <
      0.05). We conclude that an EDTA concentration lower than that used in endodontics
      decreased the substrate adherence capacity of macrophages significantly. Adhesion
      is the first step in the phagocytic process and in antigen presentation, but
      leakage of EDTA to periapical tissues during root canals preparation may inhibit
      macrophage function and reduce periapical inflammatory reactions.

PMID- 9594766
TI  - Evaluation of glass ionomer as an endodontic sealant: an in vitro study.
AB  - This study investigated the sealing ability of glass ionomer as a root canal
      sealer with and without lateral condensation of gutta percha cones. Ten gutta
      percha cones were embedded in Grossman's sealer and 10 in glass ionomer sealer.
      The sealers were mechanically separated from the gutta percha. The cone surfaces
      were examined using scanning electron microscopy (SEM). SEM revealed a
      characteristic etch pattern on the glass ionomer group and a hybrid layer on the
      cone surfaces of the Grossman's group. Additionally, 40 maxillary incisors were
      divided into four treatment groups: 1) glass ionomer sealer with lateral
      condensation, 2) glass ionomer sealer with only one master cone, 3) Grossman's
      sealer with condensation, and 4) Grossman's sealer with only one master cone. The
      average values for leakage (mm) in groups 1 through 4 were 0.81 +/- 0.75, 4.30 +/
      1.82, 0.67 +/- 0.80, and 1.10 +/- 1.68, respectively. Statistical analysis
      showed that group 2 leaked more than the other three groups.

PMID- 9594767
TI  - Cellular immuno-competence of infected root canal contents in pathogenesis of
      periapical lesions.
AB  - The soluble fractions of infected root canal contents (IRCC) were collected from
      about 300 human extracted teeth and examined for the presence of mononuclear cell
      (MNC) chemotaxis and cellular immunocompetence. IRCC showed remarkable
      chemotactic activity for polymorphonuclear leukocytes but a weak activity for
      MNC. However, generation of intrinsic MNC chemotaxis and induction of cellular
      immunity were confirmed in rats given repeated injections of IRCC.

PMID- 9594768
TI  - Torsional properties of nickel-titanium versus stainless steel endodontic files.
AB  - The purpose of this study was to evaluate and compare the torsional properties of
      stainless steel K-type .02 taper and nickel-titanium U-type .02 and .04 taper
      instruments. Torsion tests were performed on all three designs of instruments
      according to ANSI/ADA specification number 28. For each design, 20 instruments of
      each of three sizes (15, 25, and 35) were tested. The three parameters measured
      were maximum torque, torque at failure, and angular deflection. Stainless steel K
      type .02 taper and nickel-titanium U-type .02 and .04 taper instruments met or
      exceeded specification standards for maximum torque. They also satisfied and far
      exceeded the standards for angular deflection at the failure point. The stainless
      steel instruments showed no significant difference between maximum torque and
      torque at failure, whereas both of the nickel-titanium instruments showed a
      significant differential between maximum torque and torque at failure.

PMID- 9594769
TI  - Cutting ability of Heliosonic, Rispisonic, and Shaper files.
AB  - The aim of this study was to investigate the cutting ability of the Heliosonic,
      Rispisonic, and Shaper files supplied with the MM 1500 sonic handpiece. A model
      system was used and the following variables evaluated; file type (Heliosonic,
      Rispisonic or Shaper), power (air inlet ring opening of half, three quarters or
      fully open), width (15, 25 or 35), and load (25, 50 or 100 grams). A 3(4) full
      factorial analysis with two replications was performed. A new file with water
      irrigation was used for each cut. The substrate used was 1 mm thick sections of
      bovine bone. The differences between the variables were significant (ANOVA, p <
      0.001). The most significant variable to affect cutting was load, followed by
      file type, power, and width. It is suggested that operators should select the
      file type for use appropriately and press the file against the root canal wall
      for optimum cutting.

PMID- 9594770
TI  - Histologic assessment of mineral trioxide aggregate as a root-end filling in
      monkeys.
AB  - Mineral Trioxide Aggregate (MTA) has been shown in a number of experiments to be
      a potential root-end filling material. The purpose of this study was to examine
      the periradicular tissue response of monkeys to MTA and amalgam as root-end
      fillings. The pulps were removed from all the maxillary incisors of three
      monkeys. The root canals were prepared and filled with laterally condensed
      guttapercha and sealer, and the access cavities were restored with amalgam.
      Buccal mucoperiosteal flaps were raised, and root-end resections were performed
      before root-end cavity preparation with burs. The root-end cavities in half of
      the teeth were filled with MTA, while amalgam was placed in the other cavities.
      After 5 months the periradicular tissue response was evaluated histologically.
      The results showed no periradicular inflammation adjacent to five of six root
      ends filled with MTA; also five of six root ends filled with MTA had a complete
      layer of cementum over the filling. In contrast, all root ends filled with
      amalgam showed periradicular inflammation, and cementum had not formed over the
      root-end filling material, although it was present over the cut root end. Based
      on these results and previous investigations, MTA is recommended as a root-end
      filling material in man.

PMID- 9594771
TI  - Residual antimicrobial activity after canal irrigation with chlorhexidine.
AB  - We previously reported that the in vitro antimicrobial activity of a 2.0%
      chlorhexidine endodontic irrigant was equivalent to that of 5.25% sodium
      hypochlorite. The purpose of this study was to determine if chlorhexidine
      irrigants could instill substantive antimicrobial activity in instrumented root
      canals in vitro. Human teeth were instrumented using 2.0% or 0.12% chlorhexidine
      as irrigants. After instrumentation, the root canals were filled with sterile
      water, and samples of the root canal fluid were absorbed with paper points at 6,
      12, 24, 48, and 72 h after treatment. The paper points were assayed for
      antimicrobial activity by placing them on agar plate surfaces inoculated with
      Streptococcus mutans and measuring zones of inhibition. Antimicrobial activity
      was present in all 2.0% chlorhexidine-treated teeth throughout the 72-h testing
      period and in most teeth, in relatively lower concentrations, for 6 to 24 h after
      irrigation with 0.12% chlorhexidine. These results indicate that chlorhexidine
      instills substantive antimicrobial activity when used as an endodontic irrigant.

PMID- 9594772
TI  - Analysis of Ni-Ti versus stainless steel instrumentation in resin simulated
      canals.
AB  - This study compared step-back preparations in curved canals of resin blocks using
      nickel-titanium K-files and stainless steel K-files. Forty canals in resin blocks
      were cross-sectioned at 3 levels: 1 to 2 mm from the apical foramen, middle of
      the curve, and coronal. Direct digital computer images were recorded before and
      after instrumentation. Superimposition of the images combined with digital
      subtraction computer software allowed direct measurement of area instrumented,
      distance of transportation, and shape analysis. Time for instrumentation was
      recorded. Results showed Ni-Ti files to cause significantly less transportation
      and remain more centered at the apical level (p < 0.05). Area removed by
      instrumentation was significantly greater for stainless steel files at the middle
      level (p < 0.05). Cross-sectional shape of the instrumented canal was not
      significantly different (p < 0.05). It took significantly longer to prepare a
      canal with Ni-Ti K-files in resin blocks compared to stainless steel (p < 0.05).
      Resin simulated canals showed similar results compared to canals in extracted
      roots using an identical methodology.

PMID- 9594773
TI  - Factors affecting the negotiability of second mesiobuccal canals in maxillary
      molars.
AB  - Factors affecting the negotiability of MB2 canals were evaluated by studying 87
      extracted maxillary molars that had undergone previous endodontic treatment in
      the endodontic technique laboratory. The mesiobuccal roots were resected and
      radiographed, after which a #08 file was used in an attempt to negotiate those
      roots with the potential for a second mesiobuccal canal. The file was then
      intentionally separated in the MB2 canals that could be negotiated. The roots
      were decalcified, cleared, and observed under a stereomicroscope. Several factors
      that could interfere with the total or partial negotiation of MB2 canals were
      identified and included accumulation of debris and sealer that blocked access to
      these canals, dentinal debris produced with the pathfinding instrument, the
      presence of anatomical variations, diffuse calcifications, and pulp stones.

PMID- 9594774
TI  - An experimental study of the removal of cemented dowel-retained cast cores by
      ultrasonic vibration.
AB  - A technique for the removal of cemented post-cores by means of ultrasonic
      vibration was studied clinically and histologically. The removal time was
      measured for 80 extracted human teeth, including 40 single-rooted teeth and 40
      multiple rooted ones and then statistically analyzed. The periapical tissue
      reaction to the ultrasonic vibration was also examined histologically in dogs.
      The best result was achieved when lateral vibration was simultaneously given by 2
      removal tips using 2 ultrasonic generators. There was little harmful influence on
      the periodontal tissue, excluding a transient reversible reaction.

PMID- 9594775
TI  - Timing of extraction of ankylosed teeth to maximize ridge development.
AB  - Retaining an ankylosed replanted tooth during jaw growth leads to arrested
      development of the associated alveolar ridge. As the adjacent teeth erupt and the
      adjacent alveolar ridge develops, the ankylosed tooth is left in infraocclusion.
      The severity of the resulting ridge defect depends on the amount of facial growth
      after ankylosis. The extent of the defect correlates with the length of time an
      ankylosed tooth is retained during adolescent rapid growth. This case report
      illustrates the development of an extensive alveolar ridge defect when a
      replanted tooth became ankylosed and was allowed to remain through an adolescent
      growth spurt. The change in tooth position is dramatic and reflects the marked
      difference in ridge development. Clinical guidelines are presented to determine
      the optimal timing of extraction of ankylosed teeth to maximize alveolar ridge
      development.

PMID- 9594777
TI  - American Association of Endodontists' 54th Annual Session. Washington State
      Convention and Trade Center, May 7-11, 1997. Abstracts.

PMID- 9594776
TI  - Reeruption and extrusion of a traumatically intruded immature permanent incisor:
      case report.
AB  - A case report of treatment for a traumatically intruded maxillary central incisor
      is described. An attempt at accelerating eruption via surgical exposure of the
      embedded tooth was only partially successful. Orthodontic extrusion of the
      partially erupted tooth brought the tooth into correct position.

PMID- 9594778
TI  - Evaluating orofacial pain patients: psychological considerations.

PMID- 9594779
TI  - How to fire a problem patient legally.

PMID- 9594780
TI  - Rosacea.

PMID- 9594781
TI  - Basal cell carcinoma.

PMID- 9594782
TI  - A swallowed crown.

PMID- 9594783
TI  - Sale of products by dentists. ADA report and advisory opinion.

PMID- 9594784
TI  - "Treating patients with cracked teeth".

PMID- 9594786
TI  - "A systematic approach in the treatment of luxation injury".

PMID- 9594785
TI  - Topical fluoride treatment has no clinical effect on retention of pit and fissure
      sealants.

PMID- 9594787
TI  - How to evaluate a dental provider contract.

PMID- 9594788
TI  - "Restoration of the endodontically treated tooth".

PMID- 9594789
TI  - Periodontal disease and the diabetic patient.

PMID- 9594790
TI  - Xerostomia and the diabetic patient.

PMID- 9594791
TI  - Pregnancy-associated pyogenic granuloma of the lip: successful management using
      cryotherapy.

PMID- 9594792
TI  - Management of impacted third molar teeth.

PMID- 9594793
TI  - Management of traumatic root fractures: a comparison of two cases--Part 1.

PMID- 9594794
TI  - Xanthelasma palpebrarum.

PMID- 9594795
TI  - Management of traumatic root fractures: a comparison of two cases--Part II.

PMID- 9594796
TI  - Evaluating orofacial pain patients: the upper quadrant.

PMID- 9594797
TI  - Use of in-office fluorides in the Greater Houston area.
AB  - The purpose of this study was to determine the types of fluorides and techniques
      used for the application of in-office fluorides in the Houston area. A telephone
      survey was conducted using a stratified random sample of 262 dentists.
      Approximately 39% of the offices contacted chose to respond to the survey. Only
      one of the 101 dental offices responding was using an ADA approved professional
      fluoride product and technique: 1.23% APF for 4 minutes. While 41.6% or 42 of the
      respondents were using 1.23% APF, they were administering the fluoride for 2
      minutes or less with the majority (38 out of 42) administering for only 1 minute.
      The second most number of respondents (35.6%) reported using a dual rinse type
      product consisting of 0.31% APF and 1.64% SnF2. Of the 101 respondents, 12.8%
      reported the use of sodium fluoride gels and rinses. Of these 13 respondents, 9
      were using 2.0% NaF but for less than the recommended 4 minute application time.
      The other 4 were using 2.0% rinse which is more appropriate as a weekly-use
      rinse. The remaining respondents (9.8%) reported the use of a stannous fluoride
      containing less fluoride than the approved 8.0%. Of these 10 respondents, 3 were
      using 0.63% SnF2 and 7 were using 0.4% SnF2. One office reported the use of a non
      fluoride containing mouthrinse used as an in-office fluoride treatment. This
      response is not included in the data as it does not qualify as a type of fluoride
      product.

PMID- 9594798
TI  - Evaluating orofacial pain patients: avoiding tunnel vision.

PMID- 9594799
TI  - "Obstructive sleep apnea, the dentist, and two case reports".

PMID- 9594800
TI  - "Cementation--the key to success for composite resin inlays/onlays".

PMID- 9594801
TI  - Coming: a review of second-generation nonsteroidal anti-inflammatory drugs.

PMID- 9594802
TI  - "Divorce dilemmas: could I lose my practice to my ex-spouse"?

PMID- 9594803
TI  - Pregnancy gingivitis.

PMID- 9594804
TI  - Building a five-star practice.

PMID- 9594805
TI  - Herpes simplex virus-induced recurrent erythema multiforme.

PMID- 9594806
TI  - Patient complaint with previous dentist.

PMID- 9594807
TI  - "Prevention of dental malocclusions in children".

PMID- 9594808
TI  - "Antibiotic selection for endodontic infections".

PMID- 9594809
TI  - Discount coupons.

PMID- 9594810
TI  - Seborrheic keratoses.

PMID- 9594811
TI  - "Vital pulp therapy".

PMID- 9594812
TI  - Dental fluorosis caused by toothpaste ingestion: a case report.

PMID- 9594813
TI  - Treating HIV patients.

PMID- 9594814
TI  - Christian Dental Society: Belize mission trip.

PMID- 9594815
TI  - Cariogenic infection control in the management of post-irradiation caries.

PMID- 9594816
TI  - Emergency dental care.

PMID- 9594817
TI  - Provisions in lease agreements.

PMID- 9594818
TI  - Oral components of Sjogren's syndrome.

PMID- 9594819
TI  - Evaluating orofacial pain patients.

PMID- 9594820
TI  - Ethical considerations of removing serviceable amalgams.

PMID- 9594821
TI  - Donated Dental Services (DDS--Senate Bill 470).

PMID- 9594822
TI  - Onychomycosis.

PMID- 9594823
TI  - Implantology--1996 update.

PMID- 9594824
TI  - Using heat to assess pulp inflammation.

PMID- 9594826
TI  - Fabrication of an esthetic, accurate and inexpensive temporary restoration.

PMID- 9594825
TI  - Oral signs and symptoms of bulimia nervosa.

PMID- 9594827
TI  - Palatal root fracture: a case report.

PMID- 9594828
TI  - Enhancement of standardized radiographs.

PMID- 9594829
TI  - Informed consent.

PMID- 9594830
TI  - "Pediatric dentistry today".

PMID- 9594831
TI  - Case report: cyst vs. tumor.

PMID- 9594832
TI  - Long-term care requires long-term planning.

PMID- 9594834
TI  - Informed consent synopsis.

PMID- 9594833
TI  - Age-associated hair changes.

PMID- 9594835
TI  - Show me the money!! The plain truth about bonus systems and other rewards.

PMID- 9594837
TI  - Practical restoration of severely compromised vital teeth: case reports.

PMID- 9594836
TI  - Adhesive and aesthetic dentistry. A history of 4-META adhesive resins.

PMID- 9594838
TI  - Paranoia or reality?

PMID- 9594839
TI  - Long-term follow-up in hypertrophic obstructive cardiomyopathy after septal
      myectomy.
AB  - BACKGROUND: Controversy exists about the choice of treatment for patients with
      hypertrophic obstructive cardiomyopathy. The purpose of this study was to
      evaluate clinical and echocardiographic long-term results in patients with
      hypertrophic obstructive cardiomyopathy after septal myectomy and to determine
      predictors of event-free survival in these patients. METHODS: Between 1965 and
      1995, 110 consecutive patients 2 to 66 years old (mean age, 37 +/- 15 years) with
      an invasively measured left ventricular outflow tract gradient of 86 +/- 39 mm Hg
      (81 +/- 42 mm Hg by Doppler echocardiography) underwent either septal myectomy
      only (n = 87) or myectomy combined with additional procedures (n = 23). Mean
      follow-up was 11.7 +/- 7.5 years. Predictors of late events were calculated using
      multivariate Cox regression analysis. RESULTS: The perioperative mortality rate
      was 3.6% (n = 4). The cumulative survival rate at 5, 10, and 15 years was 93%,
      80%, and 72%, respectively, and symptom-free survival, 77%, 50%, and 33%,
      respectively. Predictors of late death were New York Heart Association class III
      or IV (p < 0.05), congestive heart failure (p < 0.05) and additional procedures
      (p < 0.05). The left ventricular outflow tract gradient was nearly eliminated in
      all patients, the left atrial dimension decreased significantly during the early
      years, and left ventricular dilatation occurred late in 17 patients. CONCLUSIONS:
      Septal myectomy is associated with a low perioperative mortality and a high late
      survival rate (72% at 15 years' follow-up). Septal myectomy is still an excellent
      modality in the treatment strategy for symptomatic patients with hypertrophic
      obstructive cardiomyopathy.

PMID- 9594840
TI  - Management of patients with mild aortic stenosis undergoing coronary artery
      bypass grafting.
AB  - BACKGROUND: The management of mild aortic stenosis during coronary artery bypass
      grafting remains controversial. METHODS: We reviewed the medical records of
      consecutive patients between January 1, 1977, and December 31, 1994, to identify
      51 patients with mild aortic stenosis who underwent isolated coronary artery
      bypass grafting (group A), and 19 patients with mild aortic stenosis who
      underwent combined coronary artery bypass grafting and aortic valve replacement
      (group B). Patients with more than moderate aortic regurgitation were excluded.
      Preoperative angiograms were reviewed to assess the severity of calcification and
      restricted mobility of the aortic cusps. RESULTS: In group A there were 11 deaths
      and 8 subsequent aortic valve replacements; in group B there were 5 deaths and 3
      prosthetic valve-related complications. There was no difference in event-free
      survival between the two groups after adjusting for the difference in age. Among
      group A patients, the initial transvalvular gradient (p = 0.0005) and aortic
      valvular calcification (p = 0.06) identified patients who demonstrated
      progression to severe aortic stenosis during follow-up. CONCLUSIONS: Our data
      suggest that routine aortic valve replacement during coronary artery bypass
      grafting in patients with mild aortic stenosis is not indicated, but concomitant
      aortic valve replacement may be appropriate in patients with higher transvalvular
      gradients and calcified valves.

PMID- 9594842
TI  - Cardiopulmonary bypass time does not affect cerebral blood flow.
AB  - BACKGROUND: A time-dependent decline in cerebral blood flow (CBF) has been
      reported in cardiac surgical patients despite stable pump flows and arterial
      carbon dioxide tension. Other studies have failed to support these hypothermic
      cardiopulmonary bypass (CPB) results, showing preservation of CBF during CPB. The
      purpose of the study was to define the influence of mildly hypothermic CPB
      duration on CBF. METHODS: Cerebral blood flow was measured using xenon-133
      washout and alpha-stat blood gas management during nonpulsatile CPB. Cerebral
      blood flow measurements were made after the initiation of CPB and near the end of
      bypass during pump flows of 2.4 L.min-1.m-2. RESULTS: Fifty-two coronary artery
      bypass patients were studied. The average time between CBF measurements was 54 +/
      20 minutes (mean +/- standard deviation), with a range of 10 to 100 minutes.
      Temperature and arterial carbon dioxide tension were controlled: after the
      initiation of CPB, temperature was 35.5 degrees +/- 0.4 degree C and carbon
      dioxide tension was 37 +/- 2.8 mm Hg; whereas near the end of bypass temperature
      was 35.6 degrees +/- 0.5 degree C and carbon dioxide tension was 36 +/- 2.3 mm
      Hg. We found no correlation between CBF and time on CPB (p = 0.47; r = 0.101), in
      contrast to other studies suggesting that CPB duration may intrinsically affect
      CBF. CONCLUSIONS: Our experimental results include the following: (1) during
      mildly hypothermic bypass, CBF does not decrease in relation to time and (2)
      cerebral flow-metabolism coupling is intact at 35 degrees C.

PMID- 9594841
TI  - Hypoxia increases vasodilator release from internal mammary artery and saphenous
      vein grafts.
AB  - BACKGROUND: Greater release of endothelium-derived nitric oxide is implicated in
      the superior patency of the internal mammary artery (IMA) used in coronary artery
      bypass grafting. This study compared the release of endothelium-derived nitric
      oxide into the lumen of the IMA and the saphenous vein under normoxic versus
      hypoxic conditions. METHODS: Segments of canine IMA and saphenous vein were
      perfused in vitro. Vasorelaxant activity was measured as vasodilatation of
      coronary artery smooth muscle induced by the effluent. RESULTS: Effluents from
      the IMA and saphenous vein caused comparable vasodilation of coronary artery
      smooth muscle. The vasodilatation reversed when perfusion was switched to a
      prosthetic conduit. Vasodilator activity from the IMA and saphenous vein was
      attenuated by removing the intima of the grafts or by adding N(G)-monomethyl-L
      arginine (10(-4) mol/L) or N(G)-nitro-L-arginine (10(-4) mol/L), two inhibitors
      of nitric oxide synthesis. Indomethacin attenuated vasorelaxant activity from
      saphenous vein grafts but not IMA grafts (n = 10). Vasodilator release from the
      IMA and saphenous vein was augmented by hypoxia. This augmentation was inhibited
      by indomethacin (n = 10, p < 0.05). Hypoxic augmentation reversed with return to
      normoxia. CONCLUSIONS: The release of endothelium-derived nitric oxide and
      prostacyclin from bypass grafts into the lumen, particularly during hypoxemia,
      could promote the vasodilation of distal coronary arterial beds, enhancing
      myocardial perfusion.

PMID- 9594843
TI  - Optimization of synchronization delay in latissimus dorsi dynamic
      cardiomyoplasty.
AB  - BACKGROUND: Optimal synchronization delay (SD) for triggering the implanted
      cardiomyostimulators in patients undergoing latissimus dorsi dynamic
      cardiomyoplasty has not been clearly defined. Generally a synchronization delay
      time of 45 to 60 ms is used in the current practice, in which the implanted
      cardiomyostimulator stimulates the latissimus dorsi muscle 45 to 60 ms after
      mitral valve closure acquired with M-mode echocardiography. We investigated the
      effect of shortening or prolonging the delay time on cardiac functions. METHODS:
      We studied 10 patients who were in their first 2 years postoperatively. Three
      values for SD (SD = 0 ms, 45 to 60 ms, and 150 to 160 ms) were
      echocardiographically evaluated for their influence on both systolic and
      diastolic left ventricular parameters. RESULTS: Ejection fractions were 0.27 +/-
      0.07, 0.28 +/- 0.07, and 0.32 +/- 0.06; peak aortic velocities were 0.85 +/- 0.8,
      0.86 +/- 0.11, and 0.92 +/- 0.8 m/s; and velocity-time integrals were 0.16 +/-
      0.03, 0.16 +/- 0.03, and 0.19 +/- 0.03 m for the SD values of 0, 45 to 60 ms, and
      150 to 160 ms, respectively. Diastolic parameters were also measured.
      Isovolumetric diastolic relaxation time was 97.5 +/- 49, 97.20 +/- 44, and 111.8
      +/- 49 ms; deceleration time was 83.67 +/- 32, 88.48 +/- 35, and 92.68 +/- 34 ms;
      and ratio or velocity-time integral of e wave to velocity-time integral of a wave
      was 3.09 +/- 0.98, 2.48 +/- 0.69, and 2.38 +/- 0.65 for the SD values of 0, 45 to
      60 ms, and 150 to 160 ms, respectively. Systolic functions were better when SD
      was set at 150 to 160 ms, but there was a diastolic compromise. On the other
      hand, diastolic parameters were more favorable when SD = 0 (i.e.,
      cardiomyostimulator triggered without delay) but the systolic assist was
      suboptimal. Systolic and diastolic parameters seemed relatively well-balanced
      with the current practice of setting the synchronization delay at 45 to 60 ms.
      CONCLUSIONS: The most favorable systolic effects were obtained with a prolonged
      delay of synchronization (150 to 160 ms), at some expense of diastolic functions.
      On the other hand, with a short or absent delay, diastolic parameters were
      improved but systolic parameters became suboptimal. Therefore, the current
      practice of setting the SD between 45 and 60 ms after echocardiographic mitral
      valve closure is suggested for the optimal timing for cardiomyostimulator
      stimulation in patients who have undergone latissimus dorsi dynamic
      cardiomyoplasty. Yet a great deal of individualization is necessary, and fixed
      preset values cannot definitely be determined because one setting does not fit
      all patients.

PMID- 9594844
TI  - Glucose and fatty acid oxidation by the in situ dog heart during experimental
      cooling and rewarming.
AB  - BACKGROUND: Reduced myocardial function after hypothermia may be metabolic in
      origin, but the relationship between myocardial metabolism and the various
      components of hypothermia-mediated dysfunction has not been thoroughly
      investigated. METHODS: In the present study we measured myocardial uptake and
      oxidation of glucose and oleate in mongrel dogs undergoing cooling to 25 degrees
      C followed by rewarming to 37 degrees C, using radiolabeled substrates. RESULTS:
      Segment work index declined from 39.3 +/- 5.1 to 15.1 +/- 2.4 mm Hg in response
      to cooling from 37 degrees to 25 degrees C and did not recover completely on
      rewarming (27.2 +/- 4.2 mm Hg, p < 0.05). Oleate uptake declined from 3,251 +/-
      619 to 1,043 +/- 356 nmol.min-1.100 g-1 (p < 0.05) when the dogs were cooled from
      37 degrees to 25 degrees C. Simultaneously, oxidation rate fell from 1,089 +/-
      158 to 354 +/- 83 nmol.min-1.100 g-1 (p < 0.05). On rewarming, oleate uptake was
      restored to prehypothermic values, whereas its rate of oxidation remained
      depressed (480 +/- 129 nmol.min-1.100 g-1; p < 0.05). Uptake and oxidation of
      glucose also declined significantly during cooling. However, both uptake and
      oxidation of glucose recovered fully on rewarming. CONCLUSIONS: The results of
      the present study demonstrate a reduced capacity to oxidize fatty acids by the
      myocardium during rewarming after hypothermia.

PMID- 9594845
TI  - Cardioprotection by local heating: improved myocardial salvage after ischemia and
      reperfusion.
AB  - BACKGROUND: Previous studies have shown that expression of the inducible 70-kD
      heat-shock protein (HSP72) by whole-body hyperthermia is associated with
      protection against ischemia-reperfusion injury. To develop techniques for
      regional elevation of heat-shock proteins that prevent extracardiac sequelae
      during whole-body hyperthermia, we sought to determine if local heating of the
      heart in vivo provides protection against ischemia-reperfusion injury in the rat.
      METHODS: A thermal probe was used to locally heat rat hearts at two adjacent
      sites on the epicardial surface of the left ventricle. Rats were subjected to
      either 30 minutes of sham surgery (control; n = 10) or two local applications of
      the probe at 42.5 degrees to 43.5 degrees C for 15 minutes each (n = 9). After 4
      hours, rats were subjected to 30 minutes of regional ischemia followed by 120
      minutes of reperfusion. Hearts were removed and area at risk and infarct area
      were determined. RESULTS: Localized heat stress resulted in a significant
      limitation of infarct size in heat-treated animals versus controls (mean +/-
      standard error of the mean infarct area/area at risk = 4.3% +/- 0.85 versus 19.2%
      +/- 3.4%; p < 0.005). Western blot experiments confirmed elevated HSP72
      expression in left (heated) and right (nonheated) ventricular samples from
      treated animals (n = 6; left ventricular = 5.5-fold; right ventricular = 3.7
      fold) compared with sham-operated controls. Controls treated with the probe at 37
      degrees C (n = 4) showed no increases in HSP72. CONCLUSIONS: Local heating of the
      heart is associated with elevated levels of HSP72 and improved myocardial
      salvage. The increase in expression of HSP72 is not limited to the heated region,
      but extends into nonheated regions of the heart as well. This may lead to the
      development of new techniques that improve methods of myocardial
      revascularization and heart transplantation procedures.

PMID- 9594846
TI  - Shed mediastinal blood transfusion after cardiac operations: a cost-effectiveness
      analysis.
AB  - BACKGROUND: Cardiac surgical patients consume a significant fraction of the
      annual volume of allogeneic blood transfused. Scavenged autologous blood may
      serve as a cost-effective means of conserving donated blood and avoiding
      transfusion-related complications. METHODS: This study examines 834 patients
      after cardiac operations at the University of Alabama Hospital. Data were
      collected on patients receiving unwashed, filtered, autologous transfusions from
      shed mediastinal drainage and those receiving allogeneic transfusions. The data
      were incorporated into clinical decision models; confidence intervals for
      parameters were estimated by bootstrapping sample statistics. Costs were
      estimated for transfusing both allogeneic and autologous blood. RESULTS: The
      study found a 54% reduction in transfusion risk or a mean reduction of 1.41
      allogeneic units per case (95% confidence interval, 1.04 to 1.79 units). The
      process saved between $49 and $62 per case. CONCLUSIONS: The use of autologous
      blood has the potential to significantly reduce the costs and risks associated
      with transfusing allogeneic blood after cardiac operations.

PMID- 9594847
TI  - Surgical treatment of aortic dissections: initial experience with the adventitial
      inversion technique.
AB  - BACKGROUND: The adventitial inversion technique obliterates the false lumen and
      converts a dissected aorta into a conduit with tough adventitia on the inside and
      outside. Dacron grafts can be anastomosed to the aorta with fine sutures, which
      hold without tears. METHODS: From August 1995 to March 1997, we treated 6
      patients with acute dissecting aneurysms. Three aneurysms were type I (A)
      involving the entire aorta, two type II (A) involving the ascending aorta, and
      one type III (B) involving the thoracoabdominal aorta. Circulatory arrest was
      used in 3 patients, 1 with type I aneurysm (A), 1 type II (A), and 1 type III
      (B). RESULTS: All Dacron-aorta anastomoses held sutures well and did not bleed
      intraoperatively or postoperatively. One patient (type II [A]) died of
      intraoperative low cardiac output. In patients with type I (A) aneurysms, the
      false lumen was obliterated, but 1 patient required resection of a 6-cm abdominal
      aortic aneurysm. CONCLUSIONS: The adventitial inversion technique is a safe
      technique for the treatment of acute dissecting aneurysms, which facilitates
      operation and solves the problem of intraoperative or postoperative bleeding due
      to tissue friability.

PMID- 9594848
TI  - Myocardial oxygenation during terminal warm blood cardioplegia.
AB  - BACKGROUND: Terminal warm blood cardioplegia accelerates myocardial metabolic
      recovery. The process of myocardial oxygenation during terminal warm blood
      cardioplegia and its optimal administration are not clear. METHODS: We measured
      the myocardial tissue oxygen saturation (SO2) during reperfusion using near
      infrared spectroscopy. Twenty-four dogs underwent 1 hour of ischemic arrest with
      cold crystalloid cardioplegia. They were then divided into four equal groups.
      Group 1 dogs received normal blood reperfusion. The other dogs received 15 mL/kg
      of terminal warm blood cardioplegia at 80 mm Hg in group 2 or at 60 mm Hg in
      group 3, and 30 mL/kg of cardioplegia at 60 mm Hg in group 4, followed by blood
      reperfusion. RESULTS: In group 1, the SO2 increased gradually during the early
      reperfusion and decreased transiently during the late reperfusion. In group 2,
      the SO2 increased rapidly but it decreased transiently during blood reperfusion.
      In groups 3 and 4, the SO2 increased rapidly and remained at high levels during
      the blood reperfusion. Reperfusion ventricular fibrillation occurred along with a
      SO2 decrease only in groups 1 and 2. The postischemic troponin-T levels of groups
      3 and 4 were lower than that of group 1. The functional recovery in group 4 was
      better than those in the other three groups. CONCLUSIONS: Terminal warm blood
      cardioplegia accelerates the early SO2 increase and abolishes the SO2 decrease
      during subsequent reperfusion and reduces the incidence of reperfusion
      arrhythmia, suggesting that it ameliorates reperfusion injury and consequently
      improves postischemic functional recovery.

PMID- 9594849
TI  - Continuous perfusion improves preservation of donor rat hearts: importance of the
      implantation phase.
AB  - BACKGROUND: Continuous hypothermic perfusion of donor hearts may provide extra
      protection for long ischemic times and suboptimal donors. The aim of three
      separate studies was to assess the effect of continuous hypothermic perfusion
      during simulated donor heart storage and implantation. METHODS: In study 1 twelve
      isolated rat hearts underwent 10 minutes of normothermic ischemia to simulate the
      effect of brain death on the heart and 5 hours of cardioplegic arrest, using
      University of Wisconsin solution. Six hearts were statically stored in University
      of Wisconsin solution at 2 degrees C, and six were perfused with University of
      Wisconsin solution. To assess the effect of simulated implantation, in study 2 an
      additional 12 hearts were statically stored for 5.5 hours in University of
      Wisconsin solution, six of which were rewarmed to a mean of 16 degrees C over the
      last 30 minutes of arrest. To assess the effect of simulated perfusion, in study
      3 during implantation 12 hearts were rewarmed to a mean of 16 degrees C over the
      last 30 minutes of arrest, during which time six were perfused with 2 degrees C
      solution. RESULTS: Hearts perfused during storage demonstrated greater recovery
      of prearrest power, 85.8% +/- 1.8%, than hearts preserved by static storage,
      72.7% +/- 3.0% (p < 0.01). The simulated warm implantation period reduced
      recovery of power from 68.3% +/- 5.1% to 40.2% +/- 2.0% (p < 0.001). Perfusion
      during warm implantation improved recovery to 61.8% +/- 3.9% (p < 0.01). In all
      experiments improved function was accompanied by improved metabolic energy
      status. CONCLUSIONS: During the implantation period of heart transplantation the
      donor heart sustains injury that could amount to 50% of total ischemic injury.
      Continuous perfusion during the cold storage phase and during simulated
      implantation improves recovery of the donor heart.

PMID- 9594850
TI  - Early injury to the media after saphenous vein grafting.
AB  - BACKGROUND: Injury to the smooth muscle cells of the media affects the remodeling
      process of vein grafts. The purpose of this study was to determine whether
      different techniques of surgical preparation influence the degree of medial
      smooth muscle injury. METHODS: Carotid-saphenous vein interposition grafting was
      performed in crossbred pigs (n = 32), using distended (n = 16) or nondistended (n
      = 16) conduits. After 3 to 90 days, the media was evaluated for the presence of
      smooth muscle cells (desmin stains), myofibroblast formation (transient alpha-SM
      actin expression), and apoptosis (TdT-mediated dUTP nick end-labeling [TUNEL]).
      RESULTS: Smooth muscle loss was uniformly severe; only 5% +/- 5% (p < 0.01) and
      14% +/- 9% (p < 0.01) of the medial area of distended and nondistended veins were
      desmin positive in comparison with 80% +/- 9% of controls. Apoptosis appeared to
      contribute to medial smooth muscle loss (5.7% +/- 4.3% in vein grafts versus 0.0%
      +/- 0.0% of TUNEL-positive cells in controls; p = 0.05). There was a time
      dependent increase in medial myofibroblast formation (p < 0.05). CONCLUSIONS:
      Severe medial smooth muscle loss occurs in vein grafts, even when prepared
      without distension. Apoptosis contributes to the early disappearance of smooth
      muscle cells. Adjunctive measures, in addition to ideal surgical techniques,
      should be developed to prevent medial muscle loss.

PMID- 9594851
TI  - Normothermic versus hypothermic hyperkalemic cardioplegia: effects on myocyte
      contractility.
AB  - BACKGROUND: This study was designed to determine the effects of prolonged
      hyperkalemic cardioplegic arrest under normothermic or hypothermic conditions
      with respect to left ventricular myocyte contractile performance and beta
      adrenergic responsiveness. METHODS: Isolated left ventricular porcine myocytes
      were randomly assigned to one of three groups: (group 1) normothermic control,
      (group 2) hypothermic cardioplegic arrest, or (group 3) normothermic cardioplegic
      arrest. Myocyte contractility was evaluated by high-speed video microscopy at
      baseline and after beta-adrenergic stimulation with isoproterenol (25 nmol/L).
      RESULTS: Myocyte velocity of shortening was decreased after both hypothermic and
      normothermic cardioplegic arrest (68 +/- 2 and 69 +/- 2 microns/s, respectively)
      compared with normothermic control values (96 +/- 2 microns/s; p < 0.05). This
      relative reduction in baseline contractile function was equivalent in both
      cardioplegia groups (p = 0.5356). With beta-adrenergic stimulation, myocyte
      velocity of shortening was 186 +/- 4 microns/s in the hypothermic and 176 +/- 3
      microns/s in the normothermic cardioplegia groups (p = 0.0563). However, myocyte
      contractility with beta-adrenergic stimulation was reduced in both cardioplegia
      groups compared with normothermic controls (205 +/- 4 microns/s; p < 0.05,
      respectively). CONCLUSIONS: Hyperkalemic cardioplegic arrest under either
      normothermic or hypothermic conditions resulted in an equivalent reduction in
      baseline myocyte contractile function with reperfusion/rewarming. Hypothermic
      cardioplegic arrest may have provided mild protective effects on beta-adrenergic
      responsiveness. Nevertheless, these results suggest that an important
      contributory factor for diminished myocyte contractility after simulated
      cardioplegic arrest was prolonged exposure to a hyperkalemic environment.

PMID- 9594852
TI  - Radial artery use in bypass grafting does not change digital blood flow or hand
      function.
AB  - BACKGROUND: Patient selection criteria have not been clearly established for use
      of the radial artery as a bypass conduit. To help establish such criteria, we
      measured changes in digital blood flow and hand function after radial artery
      removal. METHODS: Ninety-eight patients of the first 122 consecutive patients
      considered for radial artery harvest met predetermined criteria by vascular
      noninvasive studies to undergo removal of the radial artery. In 42 of these 98
      patients, the radial artery was actually used as a bypass conduit; 28 of these 42
      patients returned for noninvasive vascular studies, a critical review of hand
      function, and a hand symptom questionnaire. RESULTS: There were no significant
      differences between the operated and nonoperated hands for digital-brachial
      indices, cold response, grip or pinch strength, digital two-point discrimination,
      or nine-hole peg tests. The patients had an increased incidence of a small amount
      of forearm numbness and tingling, but no increase of pain or cold intolerance.
      CONCLUSIONS: For properly selected patients, there are minimal changes in hand
      function after radial artery removal.

PMID- 9594853
TI  - Growth potential and left ventricular diastolic function in cardiomyoplasty.
AB  - BACKGROUND: Dynamic cardiomyoplasty is an experimental operation for advanced
      heart failure. Current clinical results bring the possibility of its application
      to children. This study was designed to obtain information about the relationship
      between cardiomyoplasty and growth of the heart. METHODS: Six beagles, 9 to 10
      weeks old, underwent cardiomyoplasty without electric stimulation
      (cardiomyoplasty group), and another 5 beagles underwent median sternotomy and
      pericardiotomy (control group). Six months later, weights of hearts, wrapped
      latissimus dorsi muscles, and unwrapped right latissimus dorsi muscles and
      pressure-volume relationships were obtained. RESULTS: Wrapped latissimus dorsi
      muscles weighed 33 +/- 3 g (mean +/- standard deviation), and unwrapped muscles
      weighed 68 +/- 5 g. The heart weight was 82 +/- 3 g in the cardiomyoplasty group
      and 89 +/- 7 g in the control group. Left ventricular maximum elastance was 3.8
      +/- 0.8 mm Hg/mL in the cardiomyoplasty group and 3.9 +/- 0.9 mm Hg/mL in the
      control group. End-diastolic pressure versus end-diastolic volume ratios were
      0.52 +/- 0.03 and 0.54 +/- 0.05, respectively. Pathologic examination showed fat
      infiltration and muscle fiber atrophy in the cardiomyoplasty group. CONCLUSIONS:
      The wrapped latissimus dorsi muscle flaps were growing and the diastolic function
      was not impaired. This indicates a potentially safe clinical application of
      dynamic cardiomyoplasty for children.

PMID- 9594854
TI  - Surgical management of hemorrhage from rupture of the aortic arch.
AB  - BACKGROUND: Control of hemorrhage in patients with active bleeding from rupture
      of the aortic arch is difficult, because of the location of the bleeding and the
      impossibility of cross-clamping the aorta without interfering with cerebral
      perfusion. A precise and swift plan of management helped us salvage some patients
      and prompted us to review our experience. METHODS: Six patients with active
      bleeding of the aortic arch in the mediastinum and pericardial cavity (5
      patients) or left pleural cavity (1 patient), treated between 1992 and 1996, were
      reviewed. Bleeding was reduced by keeping the mediastinum under local tension (3
      patients) or by applying compression on the bleeding site (2 patients), or both
      (1 patient) while circulatory support, retransfusion of aspirated blood, and
      hypothermia were established. The diseased aortic arch was replaced during deep
      hypothermic circulatory arrest, which ranged from 25 to 40 minutes. In 3
      patients, the brain was further protected by retrograde (2 patients) or antegrade
      (1 patient) cerebral perfusion. RESULTS: Hemorrhage from the aortic arch was
      controlled in all patients. Two patients died postoperatively, one of respiratory
      failure and the other of abdominal sepsis. Recovery of neurologic function was
      assessed and complete in all patients. The 4 survivors are well 8 to 49 months
      after operation. CONCLUSIONS: An approach relying on local tamponade to reduce
      bleeding, rapid establishment of circulatory support and hypothermia,
      retransfusion of aspirated blood, and swift repair of the aortic arch under
      circulatory arrest allows salvage of patients with active bleeding from an aortic
      arch rupture.

PMID- 9594855
TI  - Intravenous aspartate infusion after a coronary operation: effects on myocardial
      metabolism and hemodynamic state.
AB  - BACKGROUND: In a previous study glutamate infusion after coronary artery bypass
      grafting was associated with beneficial effects on myocardial metabolism and
      myocardial performance. It has been claimed that aspartate is more important than
      glutamate for the recovery of myocardial metabolism after cardioplegic arrest.
      Therefore, the metabolic and hemodynamic effects of aspartate were studied after
      coronary artery bypass grafting. METHODS: Fifty to 240 mL of a 0.1 mol/L aspartic
      acid solution was infused intravenously during 60 minutes in 10 patients early
      after coronary artery bypass grafting. Myocardial metabolism was studied using
      the coronary sinus catheter technique. RESULTS: Aspartate infusion caused a
      significant increase in the arterial levels of both aspartate and glutamate. This
      was associated with a significant increase in myocardial uptake of aspartate and
      a decrease in myocardial uptake of glutamate. Myocardial exchange of other
      substrates remained unaffected. There were no changes in hemodynamic state except
      an increase of heart rate and pulmonary vascular resistance. CONCLUSIONS:
      Interactions with glutamate metabolism, compatible with competitive inhibition of
      myocardial glutamate uptake, which may have outweighed potential effects of
      aspartate, were observed. Recognition of these amino acid interactions is
      important as they are used together as additives in cardioplegic solutions.

PMID- 9594856
TI  - Cardioprotection by activation of NO/cGMP pathway after cardioplegic arrest and 8
      hour storage.
AB  - BACKGROUND: We determined whether activation of the nitric oxide/cyclic guanosine
      monophosphate pathway by sodium nitroprusside (SNP) protects hearts subjected to
      cardioplegic arrest and prolonged hypothermic storage. METHODS: Isolated rat
      hearts arrested with St. Thomas' II cardioplegia and stored at 3 degrees +/- 1
      degree C for 8 hours were reperfused at 37 degrees C in Langendorff (10 minutes)
      and working (60 minutes) modes. RESULTS: During reperfusion, left ventricular
      work was depressed in stored hearts relative to fresh hearts. When present during
      arrest, storage, and both reperfusion phases, SNP (200 mumol/L) improved work to
      values close to those in fresh hearts. When added only during the 10-minute
      period of Langendorff reperfusion, SNP also improved the subsequent recovery of
      work. This effect was antagonized by the soluble guanylyl cyclase inhibitor 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Poststorage coronary perfusion
      was not increased by SNP. CONCLUSIONS: The ability of SNP to enhance recovery
      independent of changes in coronary perfusion and in an ODQ-sensitive manner
      suggests that SNP-induced protection is due to activation of the myocardial
      nitric oxide/cyclic guanisine monophosphate pathway. These results suggest that
      supplementing cardioplegic solutions with SNP, administering SNP during early
      reperfusion, or both may offer additional means to improve donor heart
      preservation.

PMID- 9594858
TI  - Aortic valve operations under deep hypothermic circulatory arrest for the
      porcelain aorta: "no-touch" technique.
AB  - BACKGROUND: Aortic valve replacement or repair becomes a high-risk procedure in
      patients in whom the ascending aorta cannot be clamped either because of
      extensive calcification and risk of cerebral embolus or because of extensive
      adhesions precluding safe dissection and clamping. METHODS: We report the results
      of aortic valve replacement or repair with deep hypothermic circulatory arrest in
      3 patients. Techniques to improve results include routine use of epiaortic and
      transesophageal echocardiography, avoidance of manipulation of the ascending
      aorta until the circulation is arrested, avoidance of antegrade cardioplegia,
      routine use of retrograde cardioplegia and retrograde cerebral perfusion, when
      feasible, and minimal aortotomy (just enough to excise and replace or repair the
      valve). RESULTS: Operations were accomplished in approximately 1 hour each with
      minimal manipulation of the aorta, thus minimizing aortic trauma and subsequent
      risk of cerebral embolus. Each patient had an unremarkable recovery without
      neurologic complications. CONCLUSIONS: Aortic valve replacement or repair using
      the "no-touch" technique and deep hypothermic circulatory arrest is the preferred
      method when dealing with the porcelain or unclampable aorta.

PMID- 9594859
TI  - Intravenous diltiazem and acute renal failure after cardiac operations.
AB  - BACKGROUND: Perioperative administration of intravenous diltiazem to patients
      undergoing cardiac procedures has been shown to decrease the incidence of
      ischemia and arrhythmias. However, after adopting this practice in our cardiac
      surgery program, we perceived an increased incidence of postoperative renal
      dysfunction. METHODS: A directed record review of postoperative renal function
      was conducted for consecutive patients undergoing cardiac operation for the time
      periods before and after adoption of prophylactic intravenous diltiazem (0.1
      mg.kg-1.h-1 for 24 hours). The two groups were compared using chi 2 and two
      sample t tests. The risk of development of postoperative renal failure was
      modeled with logistic regression. RESULTS: Diltiazem-treated patients (n = 271)
      were similar to the control patients (n = 143) in terms of age (64 versus 61
      years; p = 0.14), ejection fraction (0.46 versus 0.47; p = 0.61), baseline serum
      creatinine level (1.2 versus 1.1 mg/dL; p = 0.27), prevalence of comorbid
      conditions, and surgical characteristics. The prevalence of left main coronary
      artery disease was lower in the diltiazem group than the control group (39%
      versus 52%; p = 0.01). During the 7-day postoperative period, the average peak
      serum creatinine level was higher in the diltiazem group (1.7 +/- 0.9 mg/dL; mean
      +/- 1 standard deviation) than the control group (1.5 +/- 0.5 mg/dL; p = 0.003).
      The incidence of acute renal failure requiring dialysis was 4.4% in the diltiazem
      group versus 0.7% in the control group (p = 0.04). There was no difference in
      length of hospitalization or mortality. The risk of acute renal failure was
      strongly associated with intravenous diltiazem (adjusted odds ratio [AOR] 6.3; p
      = 0.08), age (AOR 2.5 per 10 years; p = 0.07), baseline serum creatinine (AOR 4.8
      per 1 mg/dL; p = 0.02), the presence of left main coronary disease (AOR 5.3; p =
      0.02), and the presence of cerebrovascular disease (AOR 4.5; p = 0.05).
      CONCLUSIONS: Our retrospective analysis suggests that prophylactic use of
      intravenous diltiazem in patients undergoing cardiac operations was associated
      with increased renal dysfunction. Further studies of the risk and benefits of
      intravenous diltiazem in this setting should be undertaken.

PMID- 9594857
TI  - Heparin-coated equipment reduces the risk of oxygenator failure.
AB  - BACKGROUND: The development of an abnormal pressure gradient (APG) across the
      oxygenator is the most common cause of oxygenator failure during cardiopulmonary
      bypass. This necessitated changing the oxygenator in 4 patients in this series. A
      retrospective analysis of conditions predisposing to APG was performed. METHODS:
      One thousand nine hundred fifty-nine operations with cardiopulmonary bypass were
      performed in adults. A range of membrane oxygenators was used subject to
      availability; 769 oxygenators were heparin-coated and 1,190 were uncoated. The
      pressure gradient across the oxygenator was measured under standardized
      conditions. An APG was defined as a gradient of greater than twice the mean.
      RESULTS: An APG occurred in 44 uncoated and 3 heparin-coated oxygenators (p <
      0.001). The mean age was higher for the APG group (p < 0.001). Fibrin deposits in
      the arterial line filter were noted in 45 patients. Logistic regression revealed
      that only fibrin deposition in the arterial line filter and the use of uncoated
      oxygenators were significantly associated with APG. CONCLUSIONS: We conclude that
      a heparin-coated oxygenator effectively prevents APG. This adds significantly to
      the safety of open heart operations.

PMID- 9594860
TI  - Neuropsychologic changes after coronary artery bypass grafting: use of reliable
      change indices.
AB  - BACKGROUND: A method of defining change in neuropsychologic test scores that
      accounts for test reliability and practice effects was applied to determine
      accurately the incidence of acquired neuropsychologic deficits after coronary
      artery bypass grafting. METHODS: Neuropsychologic assessment was performed on 50
      patients before and at 7 days after either hypothermic or normothermic coronary
      artery bypass grafting. From a matched control group of 24 normal subjects who
      were examined twice over a similar interval, reliable change indices that
      controlled for measurement error and practice effects were calculated for each
      neuropsychologic measure. With the use of these indices, the incidence of
      postoperative decline among the study patients was determined. For comparison,
      the incidence of decline using the "one standard deviation" criterion also was
      calculated. RESULTS: Comparing the reliable change and standard deviation
      methods, statistically significant differences in the incidence of decline were
      observed in 5 of 11 neuropsychologic measures. The reliable change method
      identified more patients with neuropsychologic deficits on most measures.
      CONCLUSIONS: The control of measurement error and practice effects can alter
      significantly the calculated incidence of neuropsychologic impairment after
      coronary artery bypass grafting.

PMID- 9594862
TI  - Minimally invasive surgical technique for the treatment of multivessel coronary
      artery disease.
AB  - BACKGROUND: To avoid sternotomy-related complications after cardiac operations,
      we developed a minimally invasive surgical technique for the treatment of
      multivessel coronary artery disease. METHODS: From November 1996 to May 1997, 39
      patients (age range, 50 to 78 years) with coronary artery disease were treated
      with the use of this technique. Through a small (6- to 9-cm) left lateral chest
      incision in the third intercostal space, the left internal mammary artery was
      harvested directly. With the use of cardiopulmonary bypass and cardioplegic
      arrest in all patients except 1, the left internal mammary artery was anastomosed
      to the left anterior descending artery. In addition, vein grafts and other
      arterial conduits were used for revascularization of the other coronary arteries.
      RESULTS: There were no intraoperative complications. All the patients survived
      the procedure and had an uneventful postoperative course. Wound complications
      occurred in 2 patients. The median (+/- standard error of the mean) hospital stay
      was 6 +/- 1 days. CONCLUSIONS: This technique combines minimally invasive
      surgical conditions with the safety standards of routine cardiac operations. With
      the use of this approach, even extensive coronary artery disease can be treated.

PMID- 9594861
TI  - Behavior of mitral allografts in the tricuspid position in the growing sheep
      model.
AB  - BACKGROUND: On the basis of a previous experience in a chronic sheep model in
      which partial mitral allografts remained viable and properly functioning 12
      months after operation, we assessed the results obtained by replacing the
      tricuspid valve with fresh antibiotic-preserved mitral allografts. METHODS:
      Twenty 3-month-old sheep with a mean weight of 23.7 +/- 2.3 kg underwent
      cardiopulmonary bypass and had a fresh antibiotic-preserved mitral allograft
      implanted in the tricuspid position with the heart beating under normothermic
      conditions. The tricuspid valve apparatus was not excised. After a mean follow-up
      of 13.2 months, the allograft was evaluated by gross inspection and light and
      electron microscopy. RESULTS: Nine sheep died of technical causes within the
      first week after operation and 2 at 4 and 6 months of infective endocarditis of
      the allograft. The hemodynamic study before heart explantation revealed residual
      tricuspid incompetence in 3 of the 9 survivors. Macroscopic examination showed
      flexible valves with no signs of structural deterioration, calcification, or
      thrombosis. Under light and scanning electron microscopic examination, allografts
      were almost completely denuded of endothelial cells and showed loosely arranged
      connective tissue with scarce signs of inflammatory reaction. Despite these
      findings, allografts were free from major structural damage. CONCLUSIONS: The
      mitral homograft could be an alternative to replacement of the tricuspid valve
      with a bioprosthesis or a mechanical prosthesis.

PMID- 9594864
TI  - Cardiopulmonary bypass circuit treated with surface-modifying additives: a
      clinical evaluation of blood compatibility.
AB  - BACKGROUND: The cardiopulmonary bypass (CPB) circuit induces blood activation and
      a systemic inflammatory response in cardiac surgical patients. The CPB circuit
      treated with surface-modifying additive (SMA) has been found to reduce blood
      activation by in vitro and ex vivo experiments. This study evaluates the surface
      thrombogenicity and complement activation of SMA circuits during clinical CPB.
      METHODS: Twenty patients undergoing coronary artery bypass grafting were randomly
      divided into two groups. In the SMA group (n = 10), all blood-contacting surfaces
      in the CPB circuit were treated or coated with SMA, whereas in the control group
      (n = 10) patients were perfused with an identical circuit without treatment.
      RESULTS: During CPB, platelet count and beta-thromboglobulin were found similar
      in both the SMA and the control groups. Prothrombin activation indicated by
      fragment F1 + 2 was found less in the SMA group (p < 0.05). After CPB, platelet
      deposition on the CPB circuit was significantly less (p < 0.05) in the SMA group
      than in the control group as assessed by the labeled monoclonal antibody against
      platelet glycoprotein IIIa. Complement activation identified by C3a and terminal
      complex C5b-9 did not differ between the two groups, but C4a generation was less
      in the SMA group (p < 0.05). Leukocyte activation identified by elastase and
      cytokine release indicated by interleukin-8 were found uniformly in both groups.
      Postoperatively, chest tube drainage, blood transfusion, duration of ventilatory
      support, as well as the intensive care unit and hospital stay were not
      significantly different between the two groups. CONCLUSIONS: These preliminary
      clinical results suggest that SMA inhibits platelet interaction with the
      biomaterial surface of the CPB circuit. Complement activation assessed by the
      terminal complement complex is not influenced by SMA. The clinical benefit of
      this surface-modifying technique has yet to be assessed in a larger population of
      patients undergoing cardiac operations.

PMID- 9594863
TI  - Effect of nitric oxide gas on platelets during open heart operations.
AB  - BACKGROUND: The increased bleeding tendency observed after cardiopulmonary bypass
      is caused in part by thrombocytopenia and impaired platelet function induced by
      the procedure. Previous in vitro studies have shown that nitric oxide (NO) added
      to the oxygenator sweep gas reduces platelet activation during experimental
      perfusion. We evaluated the effect of 40 ppm of NO, added to the oxygenator sweep
      gas, on platelet consumption and activation in patients undergoing
      cardiopulmonary bypass. METHODS: Twenty patients scheduled to undergo
      cardiopulmonary bypass were randomized to either the control or the NO arm of the
      study. Their platelet count, plasma beta-thromboglobulin level, platelet membrane
      glycoprotein Ib and IIb/IIIa levels, adenosine diphosphate-induced platelet
      aggregation, plasma nitrate level, and plasma hemoglobin were assayed before,
      during, and after cardiopulmonary bypass. RESULTS: After operation, slightly
      higher platelet counts were observed in the NO-treated patients than in the
      control patients, which might indicate a lower degree of platelet adhesion to the
      artificial surfaces of the extracorporeal circuit. However, this difference did
      not reach statistical significance. In addition, a difference in platelet
      membrane expression of glycoprotein Ib was seen between the NO and control groups
      after operation; the platelets of the control patients had significantly higher
      glycoprotein Ib expression than those of the NO-treated patients. The results of
      platelet aggregometry indicated preserved platelet function in both the NO
      treated and control patients. The blood methemoglobin levels also were low in
      both groups. CONCLUSIONS: Nitric oxide might reduce the platelet consumption
      encountered during cardiopulmonary bypass without having any adverse effect on
      platelet function, as reflected by the preserved aggregation response seen in our
      patients. However, the best route of NO administration and the optimum dose
      remain to be established.

PMID- 9594865
TI  - Vertical displacement of the beating heart by the octopus tissue stabilizer:
      influence on coronary flow.
AB  - BACKGROUND: In beating heart coronary artery bypass graft operations,
      biventricular pump failure, as observed after exposure of the posterior
      circumflex branches by sternotomy, may originate from mechanical obstruction to
      coronary flow. METHODS: Regional coronary blood flow was measured in 8
      anesthetized, paced, beta-blocked pigs, and the beating heart was fully
      retracted. RESULTS: Displacement decreased cardiac output from 4.8 +/- 1.1 L/min
      (mean +/- standard deviation) to 2.8 +/- 1.2 L/min (p < 0.001), a 42% +/- 6%
      decrease that resulted in a decrease in mean arterial pressure by 48% +/- 6%
      (mean +/- standard error of the mean; p < 0.001) and a reduction in coronary
      blood flow in the left anterior descending coronary artery, the right coronary
      artery, and the circumflex coronary artery by 34% +/- 6%, 25% +/- 8%, and 50% +/-
      10%, respectively (all p < 0.05 versus baseline). Relative circumflex coronary
      artery flow was 20.1% +/- 8.3% lower than the combined relative value of left
      anterior descending coronary artery and right coronary artery flows (p = 0.046).
      Subsequent 20 degrees head-down tilt significantly increased ventricular preload
      pressures and restored cardiac output and mean arterial pressure as well as
      coronary blood flow. CONCLUSIONS: It is inferred that coronary blood flow was not
      mechanically obstructed during anterior displacement of the porcine beating
      heart, because augmentation of preloads by the maneuver of Trendelenburg restored
      coronary flow parallel to the recovery of cardiac output and mean arterial
      pressure while the heart remained retracted by 90 degrees.

PMID- 9594867
TI  - Evidence of vascular growth associated with laser treatment of normal canine
      myocardium.
AB  - BACKGROUND: Transmyocardial laser revascularization is a new therapy for patients
      with refractory angina. Although clinical studies suggest that transmyocardial
      laser revascularization decreases angina and may improve regional blood flow, the
      underlying mechanisms are not elucidated. We hypothesized that one mechanism may
      relate to stimulation of vascular growth in laser-treated regions. METHODS:
      Transmyocardial laser revascularization channels were made with holmium:yttrium
      aluminum garnet or carbon dioxide lasers in eight normal canine hearts; animals
      were sacrificed 2 to 3 weeks later and examined for vascular density and for
      evidence of smooth muscle proliferation. RESULTS: The original channels were
      infiltrated by granulation tissue with associated vascularity. Vascular growth
      was stimulated immediately surrounding the channel remnant as evidenced by an
      increase in the number of vessels (approximately twice that of the control
      region) and an increase in the number of vascular cells staining positive for
      markers of cellular proliferation. CONCLUSIONS: Transmyocardial laser
      revascularization leads to local vascular growth as early as 2 weeks after
      treatment. It remains to be determined whether this mechanism contributes to
      increased regional blood flow or to clinical benefits associated with this novel
      form of therapy.

PMID- 9594866
TI  - Retrograde infusion of lidocaine or L-arginine before reperfusion reduces
      myocardial infarct size.
AB  - BACKGROUND: Retrograde perfusion preserves ischemic myocardium when initiated
      shortly after coronary artery occlusion. However, benefits diminish as the delay
      increases. In this study, we used this technique to deliver agents known to
      reduce the injury associated with the reperfusion of ischemic myocardium. We
      proposed that the local delivery of lidocaine or L-arginine before reperfusion
      would reduce the damage caused during reperfusion, even after a delay between
      onset of ischemia and intervention designed to approximate clinical reality.
      METHODS: In a porcine model of myocardial ischemia, the left anterior descending
      coronary artery was snared immediately distal to its second diagonal branch.
      After 1 hour of occlusion, 34 animals were randomized into six groups: no
      intervention (control) (n = 6); administration of normal saline solution into the
      great cardiac vein (Retro-NS) (n = 6); administration of lidocaine either
      intravenously (i.v.-LID) (n = 6) or retrograde (Retro-LID) (n = 6); and
      administration of L-arginine either intravenously (i.v.-L-ARG) (n = 5) or
      retrograde (Retro-L-ARG) (n = 5). After 90 minutes of ischemia, the snare was
      released, and the myocardium was reperfused for 3 hours. Two-dimensional
      echocardiograms were made prior to occlusion and 60, 150, 210, and 270 minutes
      after occlusion. The infarct size and the area at risk were determined by
      lissamine green and triphenyltetrazolium chloride staining with computer
      planimetric quantification. Regional wall motion was assessed by a wall motion
      score: normal = 1; mild hypokinesia = 2.0; severe hypokinesia = 2.5; and akinesia
      = 3. RESULTS: The area of the left ventricle at risk for infarction was similar
      in all groups and represented 25.4% (5.2% [standard deviation]) of the left
      ventricular mass (p = 0.63). The percent area of infarction in the area at risk
      after 3 hours of reperfusion was 76.7% (7.1% for the control group, 73.9% (5.7%)
      for the Retro-NS group, 72.1% (8.7%) for the i.v.-LID group, 54.5% (10.2%) for
      the Retro-LID group, 58.8% (4.0%) for the i.v.-L-ARG group, and 54.3% (4.0%) for
      the Retro-L-ARG group p < 0.005, Retro-LID and Retro-L-ARG versus Control, Retro
      NS, and i.v.-LID; p < 0.03, i.v.-L-ARG versus control and Retro-NS). No
      significant difference in wall motion scores between groups was detected by
      echocardiography (p = 0.578). CONCLUSIONS: Retrograde delivery of lidocaine or L
      arginine before reperfusion reduces infarct size without acutely affecting wall
      motion after 90 minutes of ischemia and 3 hours of reperfusion. Lidocaine must be
      present before reperfusion to have an effect, whereas L-arginine is beneficial if
      it is delivered at the time of reperfusion.

PMID- 9594868
TI  - Modified Konno-Rastan procedure for subaortic stenosis: indications, operative
      techniques, and results.
AB  - BACKGROUND: Diffuse or unresectable subaortic stenosis (SAS) necessitates an
      aggressive surgical approach for the elimination of left ventricular outflow
      tract obstruction. In this article we report our experience with the modified
      Konno-Rastan procedure, with inherent preservation of the native aortic valve and
      annulus, in the treatment of diffuse or unresectable SAS. METHODS: Sixteen
      children (age range, 21 months to 18 years) underwent the modified Konno-Rastan
      procedure through either a transventricular (n = 12) or a transatrial approach (n
      = 4) to the conal septum. Indications for operation were recurrent SAS (n = 3),
      hypertrophic obstructive cardiomyopathy (n = 3), tunnel stenosis (n = 2), SAS
      related to a canal (n = 3), and SAS after ventricular septal defect closure (n =
      5). Eleven patients had undergone previous procedures and 5 underwent the
      modified Konno-Rastan procedure as their primary operation. RESULTS: The mean
      preoperative left ventricular outflow tract gradient of 50 +/- 17 mm Hg was
      reduced to 3 +/- 7 mm Hg (p < 0.001) after surgical repair. Postoperative
      complications included sternal infection (n = 1), heart block (n = 2),
      mediastinal bleeding (n = 1), and renal and cerebral ischemia (n = 1). There was
      1 late postoperative death caused by pneumonia 2 years after operation (6.2%
      mortality rate). The mean follow-up period was 62 +/- 39 months and all patients
      had complete relief of preoperative symptoms and were in New York Heart
      Association class I. One patient underwent a successful redo modified Konno
      Rastan procedure 7 years after the first operation for residual left ventricular
      outflow tract obstruction immediately below the aortic valve. One patient is
      awaiting reoperation for aortic incompetence unrelated to conal enlargement 1.5
      years after the first procedure. CONCLUSIONS: The modified Konno-Rastan procedure
      represents an excellent therapy for diffuse or unresectable SAS in patients with
      a normal aortic valve. In addition, it produces excellent results in a limited
      number of patients with hypertrophic obstructive cardiomyopathy, in whom the
      Morrow procedure traditionally has been performed. Although it usually is
      performed through a transventricular approach, the modified Konno-Rastan
      procedure also can be performed through a transatrial approach; this is
      particularly useful in patients who have had previous ventricular septal defect
      closure associated with SAS occurring proximal to the prosthetic patch.

PMID- 9594869
TI  - Artificial chordae for mitral valve reconstruction in children.
AB  - BACKGROUND: Congenital mitral regurgitation continues to present a challenge for
      cardiac surgeons because of the diversity of the anatomy of the congenitally
      malformed mitral valve. We undertook aggressive repair of the mitral valve with
      artificial chordae for reconstruction of the prolapsed anterior leaflet in some
      children. The short-term results are reported herein. METHODS: Three patients
      with isolated congenital mitral regurgitation underwent mitral valve repair with
      use of expanded polytetrafluoroethylene sutures as artificial chordae. RESULTS:
      There have been no late deaths and no valve-related complications. Serial follow
      up echocardiographic examinations have not revealed any increase in the severity
      of mitral regurgitation with continuing patient growth up to 39 months after the
      operation. CONCLUSIONS: When combined with other conservative methods of mitral
      valve repair, chordal replacement with expanded polytetrafluoroethylene sutures
      in children undergoing mitral valve reconstruction produces good short-term
      results. We believe that it delays and possibly prevents the need for a
      mechanical prosthesis with its associated complications in this young patient
      population.

PMID- 9594870
TI  - The surgical anatomy of the left ventricular outflow tract in hearts with
      ventricular septal defect and aortic arch obstruction.
AB  - BACKGROUND: Profound understanding of the left ventricular outflow tract (LVOT)
      anatomy is crucial to improve surgical results in patients with aortic arch
      obstruction, ventricular septal defect, and subaortic stenosis. METHODS: We
      studied the morphology of the LVOT in 32 postmortem hearts with aortic arch
      obstruction and a ventricular septal defect. In case of subaortic obstruction,
      the length of the subaortic muscular component was measured anteriorly and
      posteriorly within the left ventricle. RESULTS: Seven of the 32 hearts had no
      subaortic stenosis. Nine had aortic override, which caused LVOT narrowing.
      Sixteen hearts contained a subaortic shelf, downstream to the ventricular septal
      defect, which deviated into the left ventricle in 15. In 10 of these the shelf
      was muscular; in 6 it was a fibrous ridge. In cases with a muscular shelf, the
      posterior part was significantly shorter than the anterior part (p < 0.004). In 9
      hearts the LVOT was further narrowed because of the abnormal relationship between
      the mitral valve and the subaortic shelf. CONCLUSIONS: The present study confirms
      the complexity of LVOT stenosis in aortic arch obstruction and ventricular septal
      defect and provides a better understanding of the options to achieve surgical
      relief.

PMID- 9594871
TI  - Cardiac rhabdomyomas and obstructive left heart disease: histologically but not
      functionally benign.
AB  - BACKGROUND: Cardiac rhabdomyoma is the most common primary heart tumor in
      infants. Spontaneous regression of such tumors is common, particularly with
      smaller lesions, followed by resolution of symptoms. Based on our data on
      spontaneous involution, our institutional philosophy has been one of expectant
      management in the absence of life-threatening symptoms. However, surgical
      intervention sometimes is required for the extirpation of a rhabdomyoma from the
      left ventricular outflow tract. METHODS: A retrospective review was conducted of
      30 children in whom a rhabdomyoma was diagnosed over a 27-year period. RESULTS:
      Twenty-three percent (7/30) of the children required surgical extirpation of the
      tumor from within their left ventricular outflow tract, although a total of 94%
      had left ventricular involvement. There were no deaths. To date, no child has
      required reexcision of tumor. CONCLUSIONS: The natural history of rhabdomyoma is
      one of spontaneous regression (the 23 children who did not undergo surgical
      intervention are alive and continue to be followed up medically). We recommend
      surgical excision to alleviate acute outflow tract obstruction with reliance on
      the tumor's natural history of regression to achieve long-term freedom from
      reoperation. Although operation has been recognized as lifesaving, we were
      somewhat surprised to find that greater than 20% of our pediatric population
      required operative intervention.

PMID- 9594872
TI  - Modified superior approach for repair of supracardiac and mixed total anomalous
      pulmonary venous drainage.
AB  - BACKGROUND: The main goal in the surgical repair of total anomalous pulmonary
      venous drainage is to reestablish a wide patent connection between the common
      pulmonary vein and the left atrium. Several techniques have been proposed for
      achieving this objective, each of which has advantages and disadvantages. The
      superior approach between the superior vena cava and the ascending aorta was
      introduced in 1976 for the repair of supracardiac forms of total anomalous
      pulmonary venous drainage, but it often provides a less than optimum exposure,
      particularly in tiny infants. We proposed a modification of this approach that
      includes division of the ascending aorta and offers excellent exposure. METHODS:
      Seventeen patients (15 neonates and 2 infants) with supracardiac total anomalous
      pulmonary venous drainage (n = 13) or mixed forms of total anomalous pulmonary
      venous drainage (n = 4) underwent surgical repair with the use of the modified
      superior approach. Circulatory arrest was not required in 10 patients and the
      mean cross-clamp time was 32.5 +/- 13.8 minutes. RESULTS: There was 1
      postoperative death resulting from intractable pulmonary hypertension in a
      compromised infant who was referred to our unit receiving extracorporeal membrane
      oxygenation. One patient with common hypoplasia underwent reoperation twice at 2
      months and then 3 months after the first procedure. All the other patients had a
      smooth postoperative course, and midterm evaluation showed a widely patent
      anastomosis between the common vein and the left atrium. CONCLUSIONS: The
      modified superior approach for the repair of supracardiac total anomalous
      pulmonary venous drainage can be useful to enhance exposure during surgical
      repair and may contribute to improved patient outcome.

PMID- 9594873
TI  - Patterns and potential value of cardiac troponin I elevations after pediatric
      cardiac operations.
AB  - BACKGROUND: Perioperative myocardial injury is a major determinant of
      postoperative cardiac dysfunction for congenital heart disease, but its
      assessment during this period is difficult. The objective of this study was to
      determine the suitability of using postoperative serum concentrations of cardiac
      troponin I (cTnI) for this purpose. METHODS: Cardiac troponin I levels were
      measured serially in the serum of patients undergoing uncomplicated repairs of
      atrial septal defect (n = 23), ventricular septal defect (n = 16) or tetralogy of
      Fallot (n = 16). The concentrations were correlated with intraoperative
      parameters (cardiopulmonary bypass time, aortic cross-clamp time, and cardiac
      bypass temperature), and postoperative parameters (magnitude of inotropic
      support, duration of intubation, and postoperative intensive care and hospital
      stay). RESULTS: Postoperative absolute cTnI levels were lesion specific, with a
      pattern of increase and decrease similar for each lesion. For the total cohort,
      significant correlations between postoperative cTnI levels at all times (r = 0.43
      to 0.83, p < 0.05) until 72 hours were noted for all parameters, except for
      cardiac bypass temperature. When evaluated as individual procedure groups, no
      significant relationships were noted in the atrial septal defect group, whereas
      postoperative cTnI levels were more strongly correlated with all intraoperative
      and postoperative parameters in the ventricular septal defect group than in the
      tetralogy of Fallot group. CONCLUSIONS: This study suggests that cTnI values
      immediately after operation reflect the extent of myocardial damage from both
      incisional injury and intraoperative factors. Cardiac tropinin I levels in the
      first hours after operation for congenital heart disease are a potentially useful
      prognostic indicator for difficulty of recovery.

PMID- 9594874
TI  - Pulmonary vascular resistance of children treated with nitrogen during early
      infancy.
AB  - BACKGROUND: We have empirically used supplemental nitrogen in newborns with a
      functional single ventricle and ductal-dependent systemic perfusion to prevent
      pulmonary vasodilation and deliver a greater proportion of flow to the systemic
      circulation. Thus, we reviewed patient outcome to determine whether adverse
      pulmonary vascular effects may be associated with this therapy. METHODS: From
      December 1991 to December 1995, the fraction of inspired oxygen was adjusted,
      with supplemental nitrogen if necessary, to maintain an oxygen saturation near
      75% in 20 newborns awaiting heart transplantation. Medical records were reviewed
      to evaluate (1) the duration of nitrogen therapy, (2) pulmonary vascular
      histology, (3) postoperative pulmonary hemodynamics, and (4) survival. RESULTS:
      Thirteen patients underwent heart transplantation, 4 patients died without
      surgical intervention, and 3 patients underwent late aortic reconstruction.
      Supplemental nitrogen was used without exceeding a fraction of inspired oxygen of
      0.21 for 38 +/- 6 days. One patient had evidence of changes of potentially
      irreversible pulmonary vascular disease. Pulmonary vascular resistance was not
      increased long-term in surviving patients. CONCLUSIONS: Supplemental nitrogen can
      be used to maintain a systemic oxygen saturation near 75% for an extended period
      in newborns with ductal-dependent systemic perfusion with no long-term adverse
      effect on pulmonary vascular resistance.

PMID- 9594875
TI  - Tumor angiogenesis as a prognostic marker in operable non-small cell lung cancer.
AB  - BACKGROUND: Recent evidence suggests that tumor angiogenesis is associated with
      patient outcome in a number of malignancies. However, little is known about the
      significance of tumor microvessel density as evaluated by an anti-CD34 antibody
      in patients with lung cancer. METHODS: Tumor tissues were obtained from 101
      patients with operable non-small cell lung cancers. Immunohistochemical detection
      of tumor-associated microvessels was performed using anti-CD34 antibodies
      directed against endothelial markers. Average counts of the three most vascular
      areas on a X200 field were recorded. RESULTS: Staining for CD34 was easy to
      interpret because of specific and minimal background staining. The Kaplan-Meier
      method showed a statistically significant difference between the microvessel
      count and overall survival. The microvessel count was identified as the only
      significant and independent prognostic marker. In both univariate and
      multivariate analyses, the microvessel count was significantly related to the
      development of hematogenous metastasis but failed to associate with the
      development of nodal metastasis. CONCLUSIONS: Tumor vascularity is an independent
      prognostic factor and important for the development of hematogenous metastasis.

PMID- 9594876
TI  - Operative risk and prognostic factors of typical bronchial carcinoid tumors.
AB  - BACKGROUND: This study estimated operative risk and examined factors determining
      long-term survival after resection of typical carcinoid tumors. METHODS: From
      1976 to 1996, 139 consecutive patients (66 male and 73 female patients with a
      mean age of 47 +/- 15 years) underwent thoracotomy for typical carcinoid tumor.
      The tumors were centrally located in 102 patients (73.4%). RESULTS: Radical
      resection was performed in 106 patients (7 pneumonectomies, 13 bilobectomies, and
      86 lobectomies) and conservative resection in 33 (3 segmentectomies, 3 wedge
      resections, 20 sleeve lobectomies, and 7 sleeve bronchectomies). There were no
      postoperative deaths. Complications occurred in 19 patients (13.7%). The
      morbidity rate was not increased after bronchoplastic procedures (chi 2 = 0.033,
      not significant). Staging was pT1 in 107 patients (77.0%) and pT2 in 32 (23.0%);
      13 patients (9.4%) had nodal metastases. Seventeen patients have died (12.2%),
      during follow-up, but only three deaths were related to the disease. The overall
      survival rate at 5, 10, and 15 years was estimated to be 92.4%, 88.3%, and 76.4%,
      respectively; estimated disease-free survival was 100% at 5 years and 91.4% at 10
      and 15 years. Estimated survival of patients with lymph node metastasis was 100%
      at 5, 10, and 15 years. Univariate analysis failed to demonstrate any prognostic
      significance for sex, tumor size (T1 versus T2), tumor location (central versus
      peripheral), and type of resection. CONCLUSIONS: These data confirm an excellent
      prognosis after complete resection of typical carcinoid tumors, including those
      with lymph node metastases. Parenchyma-saving resections should be preferred.

PMID- 9594877
TI  - Surgical therapy for pulmonary aspergillosis in immunocompromised patients.
AB  - BACKGROUND: Medical management for invasive pulmonary aspergillosis (IPA) is
      often unsatisfactory. Antifungal therapy may be unable to eradicate IPA in the
      immunocompromised or neutropenic patient. METHODS: We retrospectively reviewed
      the surgical management of IPA in 13 immunocompromised patients at our
      institution. Twelve patients underwent perioperative bone marrow transplantation
      (4 autologous, 8 allogenic). All 13 patients received antifungal therapy. Eleven
      patients were neutropenic at the time of operation. RESULTS: The mean interval
      from diagnosis of aspergillosis to operation was 42 days (range, 3 to 135 days).
      Eighteen operations were performed on the 13 patients. Seven patients had
      resections from multiple pulmonary sites, whereas 6 had a single lesion resected.
      The average lesion resected was 3.7 cm in greatest diameter (range, 1 to 9 cm).
      After a mean follow-up of 21 months (range, 0 to 9 years), 3 patients (23%) are
      alive with no evidence of aspergillosis, 6 patients (46%) died without evidence
      of aspergillosis, and 4 patients (31%) died secondary to aspergillus infection.
      All 4 patients who died of aspergillus infection received an allogenic bone
      marrow transplantation. Two patients with direct extrapulmonic extension of IPA
      at time of operation died of recurrent aspergillus infections. Three of 4
      patients who died of aspergillus infection had an absolute neutrophil count less
      than 1,300 cells/microL at time of operation. The mean absolute neutrophil count
      of the patients who cleared the aspergillus infection was 5,538 cells/microL. The
      mean survival of allogenic bone marrow transplant recipients was 5.2 months, and
      for recipients of autografts was 51.4 months. CONCLUSIONS: In this series,
      surgical resection of IPA cleared the aspergillus infection in 69% of the
      patients. Neutropenia, extrapulmonic extension of IPA, and allogenic bone marrow
      transplantation may predict a worse prognosis. Surgical resection of IPA in
      immunocompromised patients is an effective form of therapy in a properly selected
      patient population.

PMID- 9594878
TI  - Isolated lung perfusion: single-pass system versus recirculating blood perfusion
      in pigs.
AB  - BACKGROUND: Cytostatic isolated lung perfusion has been advocated for treating
      pulmonary metastasis of soft tissue sarcoma. Different techniques of isolated
      lung perfusion have been developed. METHODS: Isolated lung perfusion with and
      without doxorubicin was performed on white pigs during 15 minutes either by a
      single-pass system (n = 7) or by a recirculating-blood perfusion system (n = 7).
      Three animals with endovenous drug application served as controls. Leakage was
      assessed using isotopic tracers. Perfusion-induced lung tissue injury was
      determined by postperfusion chest radiographs, by angiotensin-converting enzyme
      to-protein ratio in the plasma and in the bronchioalveolar lavage fluid, and by
      wet-to-dry weight ratio and histologic examination of lung biopsy specimens at 20
      and 50 minutes. Doxorubicin concentration in lung tissue and plasma was compared
      between the three study groups. RESULTS: All isolated lung perfusion studies were
      successfully performed without significant systemic leakage (< 0.6%). Wet-to-dry
      weight ratio was significantly lower after single-pass as compared with
      recirculating-blood perfusion and endovenous drug application at both time points
      (5.0 +/- 1.1 and 5.3 +/- 0.8 for single-pass versus 6.6 +/- 1.1 and 6.9 +/- 0.5
      for recirculating-blood versus 6.6 +/- 0.2 and 5.9 +/- 0.7 for the control group,
      respectively; p < 0.05). Angiotensin-converting enzyme-to-protein plasma ratio in
      the single-pass group was significantly lower only at 20 minutes (6.3 +/- 2.4
      versus 9.3 +/- 1.0 versus 9.7 +/- 1.9, respectively; p < 0.05) but not at 50
      minutes. Angiotensin-converting enzyme-to-protein ratio in bronchoalveolar lavage
      fluid, histology of lung biopsy specimens, and chest radiographs did not differ
      significantly between the three groups. Doxorubicin lung tissue concentration was
      not significantly different after single-pass (17.5 micrograms/g) and
      recirculating-blood perfusion (21.9 micrograms/g), but was significantly higher
      than after endovenous drug application (3.0 micrograms/g; p < 0.01). CONCLUSIONS:
      Both isolated lung perfusion techniques resulted in a sixfold to sevenfold higher
      doxorubicin lung tissue concentration than after endovenous application. Isolated
      lung perfusion-induced lung injury was similar for both techniques, but
      recirculating-blood perfusion appeared to result in more acute lung injury and
      was technically more demanding than single-pass perfusion.

PMID- 9594879
TI  - Intraoperative gamma probe-directed biopsy of asymptomatic suspected bone
      metastases.
AB  - BACKGROUND: Radioisotope bone scanning is frequently used in staging
      malignancies. However, false-positive results are common, and biopsy is usually
      required. In the absence of plain radiographic abnormalities or local symptoms,
      localization of the area of abnormal tracer activity at the time of open rib or
      sternum biopsy may be difficult. It often requires resection of a large portion
      of one or more ribs or the sternum to assure that biopsy of the target area was
      performed. In this setting, a small gamma probe underwent evaluation as an aid to
      precise intraoperative localization of increased tracer activity in the target
      bone. METHODS: Ten patients with asymptomatic suspected osseous chest metastases
      by radioisotope bone scanning but with normal plain radiographs underwent open
      biopsy of 13 ribs and 1 sternum. Six to 12 hours before operation, each received
      an intravenous injection of 28 mCi of technetium-99m oxidronate. The hand-held,
      pencil-sized gamma probe in a sterile sleeve was used to localize the area of
      greatest activity in the target bone, once the bone was exposed through a small
      incision. Biopsy of a 3-cm length of rib or portion of sternum was performed. In
      the first two rib biopsies, an intraoperative radiograph with a radiopaque marker
      on the rib confirmed that the correct rib was selected for biopsy. Intraoperative
      radiographs were not done on later cases. RESULTS: The mean ratio of hot spot
      activity on the targeted rib to background counts on adjacent ribs was 1.65 +/-
      0.22 (range, 1.35 to 2.05), and the difference was easily discernible
      intraoperatively. The ratio of hot spot activity on the sternum was somewhat
      lower (1.22), but the target area was still easy to detect. An abnormal diagnosis
      to account for the increased tracer activity was found in each of the 13 ribs and
      1 sternal biopsy in all 10 patients: metastatic squamous cell carcinoma (1 rib),
      metastatic prostatic adenocarcinoma (1 rib), lymphoma (2 ribs), localized
      hypercellular marrow (1 rib), medullary fibrosis/Paget's disease of the bone (2
      ribs), localized fibrosis/granulation tissue (1 rib), enchondroma (3 ribs), and
      chondroma (2 ribs, 1 sternum). The difference in background counts to hot spot
      activity was best with injection of the tracer 6 hours before operation.
      CONCLUSIONS: The intraoperative use of gamma counting is an easy, highly accurate
      aid (100% sensitivity) to localize areas of abnormal radioisotope uptake in
      suspected asymptomatic rib and sternal metastases. Use of this technique obviates
      the need to obtain intraoperative localizing radiographs to confirm accurate rib
      identification, thereby decreasing operative time.

PMID- 9594880
TI  - The role of esophagectomy in the management of esophageal perforations.
AB  - BACKGROUND: Despite the many advancements made in thoracic surgery, the
      management of patients with esophageal perforation remains problematic and
      controversial. METHODS: Between 1985 and 1995, 27 esophagectomies were performed
      for perforation of the thoracic esophagus. A retrospective review of the records
      of these patients was carried out, and a scoring scale developed by Elebute and
      Stoner to grade the severity of sepsis was applied. RESULTS: Among the 27
      patients undergoing esophagectomy for a perforation, the interval between rupture
      and esophagectomy was less than 24 hours in only 11 patients (40.7%).
      Postoperative surgical complications occurred in 4 patients (14.8%) and
      nonsurgical complications, in 7 (25.9%). The hospital mortality rate was 3.7%
      (1/27). In 14 patients, primary reconstruction was performed in the bed of the
      excised esophagus. There were no anastomotic leaks in this subgroup. This
      suggests that an anastomosis between viable, well-vascularized tissues is more
      important for successful healing than avoidance of some degree of contamination
      of the adjacent mediastinum. On follow-up, which averages 41 months, 73% of
      patients (16/22) have neither symptoms nor complaints. CONCLUSIONS: Esophageal
      resection definitively eliminates the source of intrathoracic sepsis, the
      perforation, and the affected esophagus. Reconstruction carried out in one stage
      does not increase operative morbidity. Esophageal resection and reconstruction is
      a valid approach even in cases of spontaneous perforation in which the diagnosis
      is markedly delayed.

PMID- 9594881
TI  - Histologic findings of transmyocardial laser channels after two hours.
AB  - Histologic examination of the human myocardium has been performed several days,
      weeks, and months after transmyocardial laser revascularization. We performed
      microscopic examinations 2 hours postoperatively. In addition to the patent
      channel (diameter, 1 mm) and a 1-to 2-mm rim of necrosis, a 1- to 3-mm zone of
      myofibrillary degeneration was found. This additional reversible injury
      immediately after transmyocardial laser revascularization could explain the
      higher mortality rate in patients with reduced left ventricular function.

PMID- 9594882
TI  - Thoracoscopic transmyocardial laser revascularization.
AB  - Transmyocardial laser revascularization has been used to treat patients with end
      stage coronary artery disease and severe disabling angina. Typically, the
      operative approach is through a left anterior thoracotomy. I report a case of
      transmyocardial laser revascularization performed thoracoscopically.

PMID- 9594883
TI  - Modified repair of mixed anomalous pulmonary venous connection.
AB  - A modified repair technique is reported for mixed total or partial anomalous
      pulmonary venous connection with the right superior pulmonary vein connecting to
      the superior vena cava, the right inferior pulmonary vein to the right atrium or
      left atrium, and the left pulmonary veins to the coronary sinus. The superior
      vena cava is transected above the highest right superior pulmonary vein, its
      cephalad end is anastomosed to the right atrial appendage, and a pericardial
      baffle is constructed between the cardiac ostium of the superior vena cava, the
      ostium of the right inferior pulmonary vein, and the left atrium, including the
      coronary sinus, which is unroofed. The reported technique may be valuable to
      avoid pulmonary venous obstruction in complex mixed forms of total or partial
      anomalous pulmonary venous connection.

PMID- 9594884
TI  - Aortocoronary bypass grafting with expanded polytetrafluoroethylene: 12-year
      patency.
AB  - Prosthetic coronary artery bypass conduits are rarely used because the rate of
      thrombosis is inherently higher than that with autologous conduits. The low
      medium-term patency rates of prosthetic grafts have restricted their use
      primarily to patients with inadequate autologous conduits or to selected
      emergencies. We describe a patient treated with expanded polytetrafluoroethylene
      who had documented patency 12 years after the operation.

PMID- 9594885
TI  - Acute normovolemic red cell exchange for cardiopulmonary bypass in sickle cell
      disease.
AB  - A patient with sickle cell disease (hematocrit, 28.5%; hemoglobin S fraction,
      79%), required mitral valve repair. Partial red cell removal and blood component
      sequestration with an autotransfusion device before cardiopulmonary bypass
      initially decreased the sickle red cell mass. This was followed by an acute one
      volume whole blood exchange transfusion performed upon the initiation of
      cardiopulmonary bypass, resulting in a further reduction. Both techniques yielded
      fresh autologous plasma for use; sequestration yielded a platelet-pheresis
      product. Adequate postbypass hemostasis was demonstrated.

PMID- 9594886
TI  - Surgical treatment of the redundant interposed colon after retrosternal
      esophagoplasty.
AB  - Redundancy of the interposed colon used as an esophageal substitute is a common
      finding in the long-term follow-up of these patients. When symptoms caused by
      food retention in the colonic loop occur, surgical correction is necessary to
      improve quality of life and to prevent aspiration. We report a technique to
      straighten the redundant colon that consists of a side-to-side colocolic
      anastomosis using a linear stapler. This obviates the need for a redo cologastric
      anastomosis. Compared with resection of the loop, the operation is quick, safe,
      and easy to perform, and it may decrease the risk of injury to the marginal
      vessels of the colon graft.

PMID- 9594887
TI  - Stentless xenograft repair of the dissected aortic root.
AB  - We used a Freestyle (Medtronic, Minneapolis, MN) porcine root to replace a
      regurgitant aortic valve and repair acute type A dissection. A Hemashield (Meadox
      Medicals, Oakland, NJ) graft was used to replace the ascending aorta with the
      "open anastomosis" technique. This method is a valuable alternative to
      conventional root replacement in acute type A dissection.

PMID- 9594888
TI  - Ross operation and mitral homograft for aortic and tricuspid valve endocarditis.
AB  - We report here a case of concomitant aortic and tricuspid valve endocarditis
      occurring in a 26-year-old woman 2 weeks after she had given birth by cesarean
      delivery. Preoperative transthoracic echocardiography revealed a previously
      undetected aorta-right atrium fistula, which at operation appeared to be
      congenital in origin. Surgical treatment consisted of aortic valve replacement
      with a pulmonary autograft, tricuspid valve replacement with a cryopreserved
      mitral homograft, and closure of the fistulous communication. The postoperative
      recovery was uneventful.

PMID- 9594889
TI  - MIDCABG followed by a gastrointestinal operation in the same anesthetic setting.
AB  - Cardiovascular complications continue to be a significant source of morbidity and
      mortality in patients having noncardiac operations. This especially is true in
      patients with known coronary artery disease facing intraabdominal operations.
      Minimally invasive direct coronary artery bypass grafting allows coronary artery
      grafting without cardiopulmonary bypass or a median sternotomy incision. Also, in
      combination with angioplasty (the "hybrid procedure"), it is possible to offer
      complete revascularization with far less surgical trauma. We present 2 cases of
      patients who had minimally invasive direct coronary artery bypass grafting
      followed by major gastrointestinal operations in the same anesthetic setting.

PMID- 9594890
TI  - Successful thrombolysis of an occluded modified Blalock shunt three days after
      operation.
AB  - A 10-day-old boy with pulmonary atresia received a right-sided aortopulmonary
      polytetrafluoroethylene shunt. Three days after the operation he became cyanotic
      and was reintubated. Shunt occlusion was confirmed with angiography. Recombinant
      tissue plasminogen activator was given locally into the proximal end of the
      shunt. The thrombus was completely resolved after 2 days. When administration of
      recombinant tissue plasminogen activator was stopped, heparin infusion was
      started for 5 days. Shunt patency was demonstrated by angiography at 3 months
      postoperatively.

PMID- 9594891
TI  - Mitral valve replacement associated with massive left atrial calcification.
AB  - Massive calcification of the atrial walls is a rare condition that entails
      important implications for mitral valve operations. Endoatriectomy is the
      procedure of choice in this situation. A technique of total replacement of the
      left atrium and mitral valve by means of a valved, T-shaped graft is presented as
      a possible alternative when a more conventional approach is not feasible.

PMID- 9594892
TI  - Unruptured aneurysm of the sinus of Valsalva into the pulmonary artery.
AB  - Congenital aneurysms of the sinus of Valsalva are rare lesions. Because the
      aortic root is central, the aneurysm can rupture into any cardiac chamber, and
      virtually all combinations of sinus and chamber fistulas have been described.
      Rupture into the pulmonary artery, however, is very rare. We encountered a 14
      year-old boy with conal ventricular septal defect and right coronary cusp
      prolapse with an unruptured aneurysm of the sinus of Valsalva into the pulmonary
      artery.

PMID- 9594893
TI  - Idiopathic saccular azygos vein aneurysm.
AB  - We present a case of asymptomatic saccular aneurysm of the azygos vein. This
      abnormality is exceedingly rare. Dynamic computed tomography revealed strong
      enhancement of the mass, suggesting a vascular structure, which was very
      important for preoperative diagnosis. It is unclear whether the mass should be
      resected if the preoperative diagnosis has been made and the mass is not so
      large.

PMID- 9594894
TI  - Giant solitary fibrous tumor of the pleura.
AB  - Solitary fibrous tumors of the pleura are rare. Approximately 600 cases have been
      described in the literature. We report a case of a young man with a giant
      solitary fibrous tumor of the pleura that filled his entire left hemithorax and
      anterior mediastinum and extended into the right side of his chest. The
      diagnostic modalities employed, the operation, and the postoperative management
      resulting in complete resection of the tumor and full lung reexpansion are
      described.

PMID- 9594895
TI  - Division of the main pulmonary artery: suboptimal palliation for the patient with
      a univentricular heart.
AB  - We describe a patient in whom a thrombus formed in the distal main pulmonary
      artery stump after a bidirectional Glenn procedure with division of the main
      pulmonary artery and in whom a restrictive inlet ventricular septal defect also
      developed. These findings emphasize the importance of maintaining antegrade flow
      through the pulmonary trunk and providing dual sources of ventricular outflow
      with a Damus-Kaye-Stansel anastomosis in patients with a univentricular heart
      without pulmonary stenosis.

PMID- 9594897
TI  - Bicuspidization for tricuspid stenosis.
AB  - Bicuspidization technique for rheumatic tricuspid stenosis based on the concept
      that the tricuspid valve has a straight (septal) and a curved (mural) leaflet is
      described. The fused commissures on either side of the septal leaflet are
      divided, resulting in separation of the two leaflets. The related anatomic and
      pathologic features are discussed.

PMID- 9594896
TI  - Broncholithiasis and thoracoabdominal actinomycosis from dropped gallstones.
AB  - We report a case of successfully managed invasive, thoracoabdominal actinomycosis
      caused by the intraperitoneal spillage of gallstones during laparoscopic
      cholecystectomy. The infected gallstones traversed the diaphragm, migrated into
      the lung parenchyma, and obstructed a segmental bronchus, causing pneumonia.
      Treatment involved retrieval of the obstructing stone, debridement and drainage
      of the pleuroperitoneal phlegmon/abscess, and intravenous antibiotics. The case
      illustrates the need to remove gallstones at the time of cholecystectomy.

PMID- 9594898
TI  - Use of 3.5-mm acetabular reconstruction plates for internal fixation of flail
      chest injuries.
AB  - The technique of using 3.5-mm acetabular reconstruction plates for multiple rib
      fractures with cerclage wires has been successful. We modified it by securing the
      reconstruction plates to the fractured ribs with cortical screws using the
      standard AO-ASIF (Arbeitsgemeindschaft fur Osteosynthesefragen [Association for
      the Study of Internal Fixation]) group technique. Our method for the internal
      fixation of the unstable chest wall is described. It is relatively simple and
      provides uniform results.

PMID- 9594899
TI  - Clamp for coronary artery operations.
AB  - Aortocoronary bypass grafting is an accepted procedure for ischemic heart
      disease. Proper visualization of the coronary artery is mandatory for good
      surgical anastomosis. This is essential when a coronary operation is performed
      without cardioplegia or in surgical procedures without bypass support. For better
      visualization of a coronary artery, we are presenting a coronary artery clamp. We
      have used this clamp in minimally invasive coronary artery operations to achieve
      a bloodless field.

PMID- 9594900
TI  - An inexpensive method of heart stabilization during coronary artery operations
      without cardiopulmonary bypass.
AB  - A method of stabilization of the heart during construction of the distal
      anastomosis in coronary artery procedures without cardiopulmonary bypass is
      described. The technique exposes and immobilizes the coronary artery, allowing a
      precise anastomosis on the beating heart. In addition, it is simple, safe, and
      inexpensive.

PMID- 9594901
TI  - A cost-effective retractor and heart stabilizer for minimal-access coronary
      bypass.
AB  - Exposure for internal mammary artery harvesting and immobilization of the
      coronary artery during the performance of minimally invasive direct coronary
      artery bypass grafting requires the use of appropriate retractors and
      instruments. We have successfully used existing retractors and instruments,
      modified for such use, which are reusable and cost effective. The use of such a
      retractor and cardiac stabilizer is described.

PMID- 9594902
TI  - Control of endoaortic clamp position during Port-Access mitral valve operations
      using transcranial Doppler echography.
AB  - The technique of computer-aided transcranial Doppler echography for continuous
      control of cerebral perfusion during minimally invasive mitral valve operations
      using the Port-Access system is described. Temporary displacement of the
      endoclamp in the aortic arch (brachiocephalic trunk, left carotid artery) is
      followed by cerebral embolic signals and a sudden decrease in the blood flow
      velocity in the middle cerebral arteries.

PMID- 9594903
TI  - Descending cervical mediastinitis.
AB  - Descending cervical mediastinitis is an uncommonly reported presentation of
      infection originating in the head or neck and descending into the mediastinum,
      which is fraught with impressive morbidity and mortality rates of 30% to 40% or
      more. We present the INOVA-Fairfax-Alexandria Hospital experience with descending
      cervical mediastinitis, January 1, 1986, to April 1, 1997; in addition we review
      the English-language medical and surgical literature with regard to this entity.
      Computed tomography and magnetic resonance imaging serve to aid both diagnosis
      and management. The application of broad-spectrum antibiotics should initially be
      empiric, with an eye to coverage of mixed aerobic and anaerobic infections.
      Definitive treatment mandates early and aggressive surgical intervention. All
      affected tissue planes, cervical and mediastinal, must be widely debrided, often
      leaving them open for frequent packing and irrigation. The treating physician
      must remain always alert to the further extension of infection, which, if it
      occurs, must be further debrided and drained. Tracheostomy serves a dual role of
      further opening cervical fascial planes and securing an often compromised airway.

PMID- 9594904
TI  - Cardiac transplantation.

PMID- 9594905
TI  - As originally published in 1989: Esophageal carcinoma: surgery without
      preoperative adjuvant chemotherapy. Updated in 1998.

PMID- 9594906
TI  - Updates to the Data Quality Review Program: the Society of Thoracic Surgeons
      Adult Cardiac National Database.
AB  - To ensure the credibility of this voluntary database, The Society of Thoracic
      Surgeons' National Database Audit and Validation Sub-Committee has been working
      during the past year to update and expand the group practice-based indicators
      used to assess the completeness, accuracy, and generalizability of the Adult
      Cardiac National Database. With increasing frequency, questions have been raised
      by third-party payors and regional/state-based groups as to the integrity of the
      data retained in the Adult Cardiac National Database. To work in conjunction with
      the Audit and Validation Sub-Committee to explicitly examine these issues, The
      Society of Thoracic Surgeons initiated a new Expert Advisory Panel review
      mechanism. This article describes the expanded data completeness and quality
      criteria that will be implemented in the coming year and summarizes the Expert
      Advisory Panel's recommendations for improvement.

PMID- 9594907
TI  - Cuffed venous return cannulas in minimally invasive cardiac operations.

PMID- 9594908
TI  - Minimally invasive mitral operations.

PMID- 9594909
TI  - Thoracoscopic transmyocardial revascularization.

PMID- 9594910
TI  - Aortic dissection during pregnancy.

PMID- 9594911
TI  - Is the elephant trunk technique really necessary for extensive arch aneurysm?

PMID- 9594912
TI  - Hybrid MIDCABG and balloon angioplasty for multivessel coronary artery disease.

PMID- 9594913
TI  - Hemivertebrectomy for apical chest tumors: is the risk justified by the outcome?

PMID- 9594914
TI  - Pseudoaneurysm of the septal branch in coronary artery bypass grafting on the
      beating heart.

PMID- 9594915
TI  - The National Cancer Data Base: ten years of growth and commitment.
AB  - The National Cancer Data Base (NCDB), now 10 years old, was created to provide a
      resource for assessing patient care and outcomes nationally and to circulate this
      information to the medical community. Dr. Partridge says the NCDB clearly has
      succeeded in fulfilling this and other goals and can be expected to continue to
      be an important source for evaluating patterns of cancer care in the United
      States.

PMID- 9594916
TI  - Clinical highlights from the National Cancer Data Base, 1998.
AB  - The National Cancer Data Base is a community-oriented cancer management and
      outcomes database that is the joint project of the Commission on Cancer of the
      American College of Surgeons and the American Cancer Society. This article
      provides a first look at highlights from the 1998 summary.

PMID- 9594917
TI  - Decision-making in radiotherapy for the cancer patient: the American College of
      Radiology Appropriateness Criteria Project.
AB  - The American College of Radiology Task Force on Appropriateness Criteria was
      developed in 1993 with the major objective of creating the most credible patient
      care guidelines possible. Oncology-related clinical conditions addressed by the
      Task Force pertain to the diagnosis of suspected disease and, after disease is
      diagnosed, its staging, treatment, and follow-up to determine the effectiveness
      of therapy.

PMID- 9594918
TI  - Improving comprehension for cancer patients with low literacy skills: strategies
      for clinicians.
AB  - This paper provides strategies to improve communication between clinicians and
      patients, particularly patients who are among the 44 million adult Americans with
      low literacy skills. Included are insights into the nature of the literacy
      problem and how it affects patient comprehension of information across the
      continuum of cancer care. Practical strategies address how to help patients
      understand medical advice, reduce literacy levels of cancer information, and help
      patients remember the advice given. A summary of the strategies is included in
      the Appendix for convenient reference.

PMID- 9594919
TI  - European Consensus Statement on Lung Cancer: risk factors and prevention. Lung
      Cancer Panel.
AB  - This article is based on discussions of the lung cancer panel at the Hohenheim
      Consensus Meeting organized by the World Health Organization and the German
      Ministry of Health in November 1996. Panel members were international experts in
      the field of diet and cancer who discussed specific questions relating to lung
      cancer risk factors and prevention.

PMID- 9594920
TI  - The role of the gamma knife in the treatment of malignant primary and metastatic
      brain tumors.
AB  - Gamma knife treatment is a clinically effective, safe, and cost-effective
      adjunctive therapy for primary malignant brain tumors. For most brain metastases,
      radiosurgery is the treatment of choice and will result in effective tumor
      control in more than 90% of treated tumors.

PMID- 9594921
TI  - The meaning of "adjusted" and "observed" survival rates.

PMID- 9594922
TI  - Smoking as a risk factor for breast cancer in women.

PMID- 9594923
TI  - Use of transesophageal echocardiography in radiofrequency catheter ablation in
      children and adolescents.
AB  - OBJECTIVE: To assess the utility of transesophageal echocardiography (TEE) in
      radiofrequency (RF) catheter ablation of left-sided atrioventricular bypass
      tracts. PATIENTS: RF catheter ablation was assisted with TEE in 13 children and
      adolescents aged 9.9 to 16.3 years (mean 13.3). Results were compared with 21
      procedures done in 19 patients (age 8.8 to 18 years, mean 14.5) without TEE
      assistance. MAIN RESULTS: RF ablation success rate was similar in both groups
      (90% to 92%). Successful RF ablation required 6 +/- 8 RF pulses in the TEE group
      and 10 +/- 7 RF pulses in the non-TEE group (nonsignificant). Fluoroscopy time
      was 36 +/- 17 mins and 54 +/- 28 mins, respectively (P = 0.03). Characteristic
      tenting of the fossa ovalis by a transseptal needle was easily visualized with
      TEE. TEE allowed for precise positioning of the ablation electrode on the mitral
      valve ring. At the successful site, the ventriculoatrial (VA) time was 42 +/- 10
      ms in the TEE group and 52 +/- 16 ms in the non-TEE group (P = 0.05). The
      atrioventricular (A:V) ratio was 1.1 +/- 1.1 and 1.2 +/- 0.7, respectively
      (nonsignificant) with a large scatter of individual values. Electrogram
      amplitudes and VA conduction times that are desirable for RF ablation were also
      recorded on the mitral valve leaflets and over the coronary sinus. TEE visualized
      thrombus formation in the right atrium (three patients) and in the left atrium
      (two patients). CONCLUSIONS: TEE should be strongly considered as supplemental
      imaging for RF ablation of left-sided bypass tracts performed under general
      anesthesia in children and adolescents. TEE renders transseptal puncture safe.
      TEE may decrease fluoroscopic exposure. TEE confirmation of the ablation catheter
      tip in the angle between the coronary sinus and the mitral valve ring may allow
      limitation of unnecessary RF lesions and injury to the mitral valve. The
      demonstration of early intracardiac thrombus formation argues for prompt and full
      heparinization after transseptal puncture.

PMID- 9594924
TI  - Calcified pseudoaneurysm of the left ventricle.
AB  - Left ventricular pseudoaneurysm following acute myocardial infarction generally
      has an extremely poor prognosis without surgical repair. A rare case of long term
      survival for 23 years following cardiac rupture with subsequent development of a
      left ventricular pseudoaneurysm after acute myocardial infarction is reported.
      The patient suffered acute inferoposterior myocardial infarction in July 1974 at
      the age of 58 years. Clinical course and findings obtained on reassessment in
      1992 (transesophageal echocardiography, chest computed tomography and left
      ventriculography) confirmed a left ventricular pseudoaneurysm. The patient
      refused surgical resection of the lesion, but remained alive and well in 1997 (81
      years old). In this case, it is considered that containment of hemorrhage by
      pericardial adhesion prevented immediate tamponade and sudden death.

PMID- 9594925
TI  - [Canadian Consensus Conference on Congenital Heart Defects in the Adult 1996].

PMID- 9594926
TI  - Medical editors clinical trial amnesty.

PMID- 9594927
TI  - Lipid altering or antioxidant vitamins for patients with coronary disease and
      very low HDL cholesterol? The HDL-Atherosclerosis Treatment Study Design.
AB  - Evidence supports the idea that substantial benefits may derive from treatments
      that increase high density lipoprotein (HDL) cholesterol (HDL-C), apolipoprotein
      (apo) A-I, HDL2 (or 2b) or the size of HDL particles with, or without, apo A-II.
      HDL3 appears to be neutral in terms of coronary artery disease risk, and apo A-II
      appears to be adverse. Because HDL particles serve as antioxidants in vitro, the
      hypothesis that low HDL-C reflects an antioxidant deficiency state appears
      tenable. Based on these observations, a three-year angiographic study was
      proposed and received funding. Enrollment began in January 1995 and was completed
      in January 1997.

PMID- 9594928
TI  - Economic aspects of hypercholesterolemia treatment with HMG-CoA reductase
      inhibitors: a review of recent developments.
AB  - Recent literature on the cost effectiveness of hepatic hydroxy-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors in the treatment of
      hypercholesterolemia is reviewed with a twofold objective. First, the relative
      cost effectiveness of treatment with HMG-CoA reductase inhibitors is compared
      with that of other interventions based on recent long term morbidity and
      mortality trials; and second, drugs within this therapeutic class are identified
      that produce the desired effect at minimum cost. Given the limited resources
      available to treat hypercholesterolemia, the question of establishing which
      subgroup of the population is most likely to benefit from treatment with statins
      is legitimate. The latest economic evidence is used to demonstrate that the most
      cost effective public health strategy is to identify the patient population that
      needs to be treated and to select the most cost effective treatment.

PMID- 9594929
TI  - Rationale for and outline of the recommendations of the Working Group on
      Hypercholesterolemia and Other Dyslipidemias: interim report. Dyslipidemia
      Working Group of Health Canada.
AB  - A panel consisting of lipidologists, epidemiologists, cardiologists, internists,
      general practitioners, and public health and government representatives used the
      evidence-based approach to examine the rationale for a draft of recommendations
      for medical management of lipid disorders. The proposed recommendations deal with
      assessment of cardiovascular risk based on history, physical examination and
      laboratory findings; assessment of the fasting lipid profile; diagnosis and
      treatment of secondary risk factors; calculation of the 10-year risk of a cardiac
      event; initiation of lifestyle modifications in patients in whom low density
      lipoprotein cholesterol (LDL-C), total:high density lipoprotein cholesterol (HDL
      C) ratio or triglycerides exceeds target values based on a patient's risk
      category; follow-up; treatment with drugs; and choices of drugs. In contrast to
      previous recommendations, there are new, considerably lower, cholesterol level
      targets for secondary prevention, with a less important emphasis on total
      cholesterol value than on LDL-C or total:HDL-C ratio and triglyceride levels, and
      an emphasis on determining the likelihood of a cardiac event by evaluating all
      relevant risk factors and sharpening the focus on nondrug treatment, which should
      result in treating a greater percentage of at-risk patients.

PMID- 9594930
TI  - Taking AIM: how to teach primary and secondary prevention effectively.
AB  - Optimization of lifestyle factors by quitting smoking, losing weight, eating
      right and starting an exercise regimen is the cornerstone of treatment for
      dyslipidemias, diabetes and heart disease. Any health care practitioner who has
      recommended lifestyle changes to a patient knows the inherent difficulty for most
      patients who try to implement and adhere to such behaviour changes. Patient
      education is a fundamental component of comprehensive clinical care and is a
      necessary antecedent to behaviour change. Through effective patient education,
      patients can learn primary and secondary prevention strategies, decrease their
      risk status and make better lifestyle choices in order to optimize their health
      and well being. Providing patient education, however, can be a complex task and
      requires the health care practitioner to go beyond simply telling the patient
      what to do. How can health care providers be more effective in their teaching
      efforts? Integrating key theoretical perspectives on patient education and using
      a sound, consistent approach in teaching patients will improve the efficacy of
      patient education and ensure a more proficient implementation of this role in the
      context of clinical practice. Taking 'AIM' is one such approach: Assess the
      learner, Identify barriers to learning, and Motivate the patient to make changes.

PMID- 9594931
TI  - The need for revascularization procedures will remain the same or increase in the
      next decade.
AB  - It has been stated that cardiovascular risk-reduction strategies such as lipid
      lowering drug therapy will significantly decrease the need for coronary
      revascularization procedures nationally and worldwide by the end of the next
      decade. Because of a number of factors this decrease is unlikely to occur. First,
      there is every indication that the growth of the Canadian population will remain
      at least linear in the next decade. In addition, the population is aging, with
      the greatest increase in population occurring in the 'baby boom' group and those
      older. This phenomenon will place an unprecedented level of stress not only on
      the health care system in general but also on all services related to the care of
      patients with symptomatic coronary artery disease. It has been suggested that
      these increases will be offset by proven therapies to reduce the risk of
      cardiovascular events. However, studies show that therapies such as lipid
      lowering drugs continue to be underused, due to physician as well as patient
      factors. Furthermore, the indications for coronary revascularization are
      expanding with new evidence showing benefits of direct PTCA in the setting of
      myocardial infarction, as well as cardiogenic shock in selected patients. In
      addition, PTCA of totally occluded coronary arteries will be performed more
      frequently with new studies showing benefits in this setting. The greatest impact
      on need for revascularization procedures will occur worldwide. The coronary
      artery disease epidemic that affected western society is just now beginning to
      emerge in developing countries. Studies in India and China show an alarming rise
      in the prevalence of cardiovascular risk factors and with it the rise in the
      shift of the burden of disease from infectious to cardiovascular etiology. All of
      these factors are likely to result in an unprecedented rise in the need for
      coronary revascularization procedures.

PMID- 9594932
TI  - The need for revascularization procedures will decrease dramatically in the next
      decade.
AB  - Coronary revascularization, first with coronary artery bypass graft (CABG)
      surgery and later using percutaneous transluminal coronary angioplasty (PTCA),
      has been available as a treatment procedure for patients with anginal syndromes
      for over three decades. During this time, the number of procedures performed has
      risen exponentially. The most recent development has been the growing trend away
      from CABG towards PTCA. Despite these facts, it is argued that the need for
      coronary revascularization will decrease over the next decade and the reasons
      that underlie this provocative prediction are discussed. Scientific (both
      pathophysiological and epidemiological) and historical precedent with other
      surgical procedures that have disappeared completely from medical practice are
      used to substantiate this argument.

PMID- 9594933
TI  - Portal hypertension.

PMID- 9594934
TI  - Causative pathogens in onychomycosis and the possibility of treatment resistance:
      a review.
AB  - Onychomycosis is caused primarily by dermatophytes, Candida species, and
      nondermatophytic molds. Dermatophytes, particularly Trichophyton rubrum, are by
      far the most common pathogens. There is some question as to whether Candida
      actually breaks down nail material or only invades the proximal nail bed.
      Similarly, the clinical significance of molds is unknown, because they may be
      colonizing organisms rather than destructive pathogens. It is, therefore,
      important to identify the pathogen in the array of organisms that may be isolated
      in culture. The increasing use of fluconazole in prophylaxis and treatment of
      systemic yeast infections and infections in patients with AIDS has been
      associated with the emergence of resistant Candida albicans, as well as
      previously minority species of Candida, such as C. glabrata and C. krusei. This
      may be of relevance to the treatment of onychomycosis with azole antifungals.

PMID- 9594935
TI  - Fungicidal versus fungistatic activity of terbinafine and itraconazole: an in
      vitro comparison.
AB  - BACKGROUND: The ratio of fungicidal to fungistatic activity of two new antifungal
      agents, itraconazole and terbinafine, against the causative organisms in
      onychomycosis may have clinical relevance. OBJECTIVE: This study compared the
      fungistatic and fungicidal activity of terbinafine and itraconazole against
      clinical isolates of dermatophytes and Candida species causing onychomycosis.
      METHODS: The antifungal agent was added to suspensions of dermatophyte conidia
      and hyphal fragments (5 x 10(3) to 5 x 10(4) fungal elements/ml) that had been
      preincubated to allow hyphal formation. Cell suspensions of Candida species (1 to
      5 x 10(3) cells/ml) were not preincubated before drug exposure. Macrobroth and
      macrobroth dilution assays were used to test antifungal susceptibility of
      dermatophytes and yeasts, respectively. An agent was considered fungicidal if the
      minimal fungicidal concentration (MFC) to minimal inhibitory concentration (MIC)
      ratio was < or = 4 and fungistatic if the ratio was > 4. Cell death was also
      visualized by a vital stain. RESULTS: For both itraconazole and terbinafine, the
      MIC for dermatophytes was low. The MFCs and MFC/MIC ratios for terbinafine
      against dermatophytes were lower than for itraconazole; the fungicidal activity
      of terbinafine was excellent and initiated rapidly (by 7 hours) and that of
      itraconazole was poor (fungicidal activity was not evident until 10 to 12 hours).
      For yeasts, the MICs were higher than for dermatophytes, and the differences
      between itraconazole and terbinafine were less pronounced. CONCLUSION: Both
      itraconazole and terbinafine inhibit growth of dermatophytes. The more rapid
      fungicidal activity of terbinafine may have clinical relevance in the treatment
      of onychomycosis.

PMID- 9594937
TI  - Systemic antifungal agents used to treat onychomycosis.

PMID- 9594936
TI  - Pharmacokinetics and pharmacology of terbinafine and itraconazole.
AB  - BACKGROUND: Two new systemic antifungal agents, terbinafine and itraconazole,
      have expanded the choices for treatment of onychomycosis. The pharmacokinetic and
      pharmacologic properties provide the basis of their activity and are related to
      their efficacy and safety in dermatophyte infections. OBJECTIVE: We describe the
      pharmacodynamics, pharmacokinetics, and pharmacology of terbinafine and
      itraconazole and the features that form a framework for comparing their efficacy.
      PHARMACODYNAMICS: Both terbinafine and itraconazole ultimately block ergosterol
      synthesis; terbinafine disrupts fungal cell wall synthesis earlier (squalene to
      squalene epoxide) than does itraconazole (lanosterol to ergosterol). In vitro,
      terbinafine exposure results in a toxic accumulation of squalene and decreased
      production of ergosterol. Minimal inhibitory concentrations (MICs) of terbinafine
      for dermatophytes are essentially equal to minimal fungicidal concentrations
      (MFCs). However, the MFCs of itraconazole are much higher than the MICs.
      PHARMACOLOGIC PROFILE: Both itraconazole and terbinafine penetrate keratinizing
      tissue; levels reached in nail plate exceed those in plasma. Therapeutic levels
      of the itraconazole persist in nails for up to 6 months after discontinuation of
      3 months of therapy (200 mg/day) and during various pulsed cycles. After
      discontinuation of 1 month of therapy, terbinafine persists at therapeutic levels
      in the nail. Itraconazole has an affinity for mammalian cytochrome P-450 enzymes
      as well as for fungal P-450-dependent enzyme, and thus has the potential for
      clinically important interactions (e.g., astemizole, terfenadine, rifampin, oral
      contraceptives, H2 receptor antagonists, warfarin, cyclosporine). Terbinafine is
      not metabolized through this system and has little potential for drug-drug
      interactions. CONCLUSION: The low MFCs exhibited by terbinafine for dermatophytes
      may be important in its clinical efficacy and low relapse rates. The safety
      profile of terbinafine directly reflects its mechanism of action.

PMID- 9594938
TI  - Terbinafine versus itraconazole: a controlled clinical comparison in
      onychomycosis of the toenails.
AB  - BACKGROUND: Because of the relative clinical inefficacy of antifungal therapy in
      the past, onychomycosis has largely been viewed as an incurable condition. The
      availability of two new oral antifungal agents suggests the possibility of
      revising this clinical precept. OBJECTIVE: This study compared the efficacy and
      tolerability of terbinafine and itraconazole in the treatment of onychomycosis of
      the toenails. METHODS: This investigation was a multicenter, double-blind,
      parallel group study. The primary therapeutic endpoints measured were mycologic
      cure and clinical improvement. RESULTS: Mycologic cure rates (negative culture
      and microscopy) at the end of the study were 81% for terbinafine versus 63% for
      itraconazole (2p < 0.01). A total of 92% of terbinafine-treated patients had
      negative cultures at the end of the study, compared with 67% of itraconazole
      treated patients (2p < 0.0001). Terbinafine was more effective than itraconazole
      in increasing the length of the unaffected area of the target nail: 9.44 mm
      versus 7.85 mm (2p < 0.05). CONCLUSION: Terbinafine is more effective than
      itraconazole in the treatment of toenail onychomycosis.

PMID- 9594939
TI  - Twelve weeks of continuous oral therapy for toenail onychomycosis caused by
      dermatophytes: a double-blind comparative trial of terbinafine 250 mg/day versus
      itraconazole 200 mg/day.
AB  - BACKGROUND: Dermatophyte infections of the toenail have been difficult to treat,
      requiring long courses of therapy and having high recurrence rates. New oral
      antifungal agents with better outcomes and minimal adverse events are needed.
      OBJECTIVE: The purpose of this study was to compare two newer antifungal
      compounds, terbinafine and itraconazole, for efficacy and safety in toenail
      onychomycosis caused by dermatophytes. METHODS: The study was randomized and
      double-blind. It compared 12 weeks of continuous oral treatment with terbinafine
      250 mg/day or itraconazole 200 mg/day for confirmed toenail dermatophyte
      onychomycosis. Clinical symptoms and mycologic outcome were assessed at weeks 4,
      8, 12, 24, 36, and 48. A total of 372 patients (186 in each group) with
      dermatophyte infection confirmed by microscopy and culture were included in the
      intent-to-treat analysis. RESULTS: At week 48, a statistically significantly
      greater percentage of the terbinafine group than itraconazole group showed
      negative mycology (73% [119 of 163] vs 45.8% [77 of 168]; p < 0.0001) (difference
      = 27.2%; 95% CI = [17.0%, 37.3%]). The difference was also confirmed clinically
      (p = 0.001) in the patients who were clinically cured or had only minimal
      symptoms at the end of the study (76.2% [125 of 164] vs 58.1% [100 of 172])
      (difference = 18.1%; 95% CI = [8.24%, 27.9%]). The geometric mean length of
      healthy nail of the big toe was significantly greater in the terbinafine than
      itraconazole group (8.1 vs 6.4 mm; p = 0.026). Tolerability was good to very good
      in almost 90% of patients in both groups, and all reported adverse events were
      known for these compounds. CONCLUSION: Terbinafine produced higher rates of
      clinical and mycologic cure at follow-up than did itraconazole.

PMID- 9594940
TI  - Measuring health-related quality of life in onychomycosis.
AB  - BACKGROUND: Patients with onychomycosis may experience physical impairment and
      psychological and social limitations related to their infection. OBJECTIVE: The
      object of this study was to compare health-related quality-of-life scores of
      patients with onychomycosis with those of a control group. METHODS: The interview
      instrument included scales of general measures, disease-specific factors, and
      issues specifically related to onychomycosis symptoms; the onychomycosis group
      also was questioned about past treatment and attitude towards treatment. RESULTS:
      A total of 299 persons with onychomycosis and 381 controls were interviewed.
      Demographic factors were similar except for gender and age. Analyses adjusted for
      these differences. All general quality-of-life scores but one were significantly
      lower in the onychomycosis group. For responses to questions related specifically
      to nails, the onychomycosis group reported significantly more problems with
      physical appearance than did controls (p < 0.001); the greatest absolute
      differences were for physical activities involving the feet. The majority (88%)
      of the onychomycosis group indicated they would take oral medication even if it
      had short-term side effects. CONCLUSION: Onychomycosis affects generic health
      related quality-of-life measures less than other variables. The greatest impact
      is on onychomycosis-specific measures. Because patients are willing to try
      treatment, many of these quality-of-life concerns can be addressed by newer oral
      treatments.

PMID- 9594941
TI  - Cost-effectiveness of two new treatments for onychomycosis: an analysis of two
      comparative clinical trials.
AB  - BACKGROUND: Pharmacoeconomic analyses are becoming an increasingly integral
      component of the overall profile of new drugs. This is particularly true for
      terbinafine and itraconazole, because both agents have been shown to be
      clinically effective and relatively safe. OBJECTIVE: This study examined the cost
      effectiveness of terbinafine and itraconazole in two recent comparative clinical
      trials of these new agents for onychomycosis of the toenails. METHODS: Data as
      reported in the two clinical trials were used as the basis for an analytic
      decision-tree model that included cost of drug, medical management of the disease
      and any adverse reactions, and clinical efficacy data into calculations that
      estimated the relative cost effectiveness ratio for each drug on the basis of
      cost per disease-free day. RESULTS: The total cost of terbinafine therapy ranged
      from $697.55 to $699.11, and the total cost of itraconazole therapy ranged from
      $1216.40 to $1218.80. The expected cost per disease-free day of itraconazole was
      $2.05 and $2.37, in the Brautigam and De Backer trials, respectively; similar
      costs for terbinafine were $1.27 and $1.50. Relative to terbinafine, which was
      assigned a value of 1.0, the cost-effectiveness ratio of itraconazole was 1.62
      and 1.58 in each trial, indicating a lower cost-effectiveness than terbinafine.
      CONCLUSION: Terbinafine is more cost-effective than itraconazole in the treatment
      of toenail onychomycosis.

PMID- 9594942
TI  - Rugby and spinal injury: what can be done?

PMID- 9594943
TI  - Services for sexual health: where should they be provided?

PMID- 9594944
TI  - Carrier testing for cystic fibrosis.

PMID- 9594945
TI  - Panic disorder and coronary artery spasm.

PMID- 9594946
TI  - Severe cervical spinal cord injuries related to rugby union and league football
      in New South Wales, 1984-1996.
AB  - OBJECTIVE: To determine the frequency and circumstances of serious cervical cord
      injuries associated with rugby union and league football in New South Wales.
      DESIGN: Retrospective review of patients with rugby football-related cervical
      spinal cord injuries. SETTING: The two central spinal units in NSW, from January
      1984 to July 1996. OUTCOME MEASURES: Admission to spinal units; injury resulting
      in permanent tetraplegia. RESULTS: During the review period, 115 rugby football
      players (56 union and 59 league) were admitted to the spinal units because of
      cervical spinal cord injuries. 49 patients had resultant permanent neurological
      deficits (complete tetraplegia [quadriplegia])--26 associated with rugby union
      and 23 with rugby league. Two patients died of injury sequelae within two weeks
      of admission. There was no significant change in the rate of football-related
      admissions to spinal units for either code. There was a small decline in the
      number (from 15 in 1984 to 1987 to 7 in 1992 to 1996) and incidence (from 1.2 to
      0.5 per 10,000 participants) of patients with tetraplegia associated with rugby
      union. When this decline was tested as a trend over the years, it was found to be
      statistically significant (P = 0.06). No significant trend was found in the
      tetraplegia data associated with rugby league. Cervical spinal cord injuries
      leading to complete tetraplegia were most commonly associated with scrum-like
      plays in union and with tackles in league. CONCLUSION: Serious cervical spinal
      injuries associated with both codes of rugby continue to occur in NSW. Rugby
      football in its various forms is still an inherently dangerous game.

PMID- 9594947
TI  - Community screening for colorectal cancer in north-eastern New South Wales, 1987
      1996.
AB  - OBJECTIVE: To analyse results of Bowelscan, a community-based colorectal cancer
      screening program using Hemoccult II, and targeting people aged 40 years and
      over. DESIGN: Survey of data from medical practitioners on follow-up of positive
      tests. SETTING: North-eastern New South Wales (Rotary District 9650), 1987-1996.
      SUBJECTS: 3845 people with positive results for faecal occult blood. OUTCOME
      MEASURES: Investigations performed; final diagnoses; number, site and Dukes'
      stage of colorectal carcinomas; number and histological diagnosis of colorectal
      polyps. RESULTS: 239,500 Hemoccult II kits were distributed between 1987 and
      1996, with an estimated return rate of 80%-85%. Positive results for faecal
      occult blood were reported for 3845 tests (1.6% of those distributed), with 78%
      of these investigated by colonoscopy and/or barium enema. Investigation resulted
      in diagnosis of 260 colorectal carcinomas in 252 people (6.7%); 74 of these (29%)
      were in the caecum or ascending or transverse colon. Dukes' tumour stages were:
      A, 107 (41%); B, 86 (33%); C, 49 (19%); D, 16 (6%); and unknown, 2 (0.8%).
      (Corresponding figures from the NSW Central Cancer Registry were: A and B, 48%;
      C, 26%; D, 14% and unknown 12%) [corrected]. Colorectal polyps were found in a
      further 819 people (21.3%), and were adenomatous in 577 (79% of the 733 in whom
      histological diagnosis was available). Other gastrointestinal conditions were
      found in 1343 people (34.9%), while no cause was found for the positive result,
      despite adequate investigation, in 873 (22.7%). CONCLUSION: Community-based
      screening with faecal occult blood testing detected colorectal carcinomas at
      earlier histological stages than colorectal carcinomas reported to the Cancer
      Registry and should reduce mortality from this disease. Treatment and follow-up
      of adenomatous polyps detected by such a program might minimise the incidence of
      colorectal carcinoma in this group.

PMID- 9594948
TI  - Women's satisfaction with general practice consultations.
AB  - OBJECTIVE: To determine women's satisfaction with general practice services.
      DESIGN: Cross-sectional postal questionnaire conducted during April to September
      1996 (part of the baseline survey of the Australian Longitudinal Study on Women's
      Health). PARTICIPANTS: Women aged 18-22 (n = 14,739), 45-49 (n = 14,013) and 70
      74 (n = 12,941) years, randomly selected from the Medicare database, with
      oversampling of women from rural and remote areas. MAIN OUTCOME MEASURES:
      Frequency of use of general practice services; satisfaction with the most recent
      visit to a general practitioner (GP); prevalence of selected symptoms; preference
      for a female doctor. RESULTS: The most recent visit to a GP was rated overall as
      good, very good or excellent by more than 80% of women, with increasing levels of
      satisfaction with increasing age of the women. However, satisfaction was lower
      for waiting room time and cost of the visit. A third of the young and middle-aged
      women living in rural and remote areas were dissatisfied with the cost of the
      visit. Young women were more likely to prefer a female doctor, and many were
      dissatisfied with their GP's skills at explaining their problem and giving them a
      chance to give an opinion and ask questions. The most prevalent symptoms for all
      women included headaches and tiredness, and may were not satisfied with the
      health services available to help them deal with these symptoms. CONCLUSIONS:
      Australian women have high levels of satisfaction with GP consultations. However,
      more effective strategies may be needed to improve communication with younger
      women, and there is an unmet need for services to help all women deal with some
      common symptoms. Dissatisfaction with cost of services and women's preference for
      female doctors have implications for future health policy.

PMID- 9594949
TI  - Panic disorder: coronary spasm as a basis for cardiac risk?
AB  - Patients with panic disorder often complain of angina-like chest pain during
      panic attacks, but this is not usually considered life-threatening. We describe
      three patients with panic disorder and documented cardiac ischaemia during
      episodes of chest pain. In two, it progressed to myocardial infarction. As none
      had atherosclerosis evident at coronary angiography, the mechanism was presumed
      to be coronary artery spasm. These cases illustrate that pain typical of angina
      during panic attacks may have an organic cause.

PMID- 9594951
TI  - Fibromyalgia syndrome and disability: the neurogenic model.

PMID- 9594950
TI  - Looking forward, looking back.

PMID- 9594952
TI  - Fibromyalgia syndrome and disability: a failed construct fails those in pain.

PMID- 9594953
TI  - Drug-related hospital admissions: a review of Australian studies published 1988
      1996.
AB  - OBJECTIVE: To examine the extent of drug-related hospital admissions in Australia
      by reviewing Australian studies published between 1988 and 1996. DATA SOURCES AND
      STUDY SELECTION: The terms "drug-related", "admissions", "readmissions",
      "hospitalisation", "hospitalization" and "iatrogenic" were used to search MEDLINE
      and Australian Public Affairs Information Service databases. The Australian
      Journal of Hospital Pharmacy and conference proceedings of the Society of
      Hospital Pharmacists and the Australasian Pharmaceutical Science Association were
      searched manually. Studies were included if they were Australian, had the primary
      aim of identifying drug-related admissions, and had at least one clinical
      pharmacist or medical practitioner review the admissions. DATA EXTRACTION: Total
      number of admissions assessed; proportion considered drug-related; drug groups
      implicated; and proportion considered avoidable. DATA SYNTHESIS: 14 studies were
      identified; 2.4%-3.6% of all hospital admissions were reported to be drug
      related. 6%-7% of emergency admissions, 12% of all admissions to medical wards
      and 15%-22% of all emergency admissions among the elderly were drug related.
      Between 32% and 69% of drug-related admissions were reported as definitely or
      possibly preventable. Drug groups most commonly implicated were cytotoxics,
      cardiovascular agents, antihypertensives, anticoagulants and non-steroidal anti
      inflammatory drugs. CONCLUSION: Drug-related hospital admissions are a
      significant and expensive public health problem in Australia, and approximately
      half were considered possibly or probably preventable.

PMID- 9594954
TI  - Anti-obesity drugs.

PMID- 9594955
TI  - Increase in spinal injury among rugby union players in Fiji.

PMID- 9594956
TI  - Reducing brain damage in boxers.

PMID- 9594957
TI  - Metastasis from atypical fibroxanthoma of skin.

PMID- 9594958
TI  - Early discharge and risk for postnatal depression.

PMID- 9594959
TI  - Early discharge and risk for postnatal depression.

PMID- 9594960
TI  - Early discharge after childbirth: too late for a randomised trial?

PMID- 9594961
TI  - Schizophrenia and influenza in Palau.

PMID- 9594962
TI  - Rationing and the objectives of health care.

PMID- 9594963
TI  - Probable association between Barmah Forest virus infection and Guillain-Barre
      syndrome.

PMID- 9594964
TI  - Aboriginality as a variable in epidemiology.

PMID- 9594965
TI  - Castor oil seed poisoning: a concern for children.

PMID- 9594966
TI  - The emerging role of the dendritic cell in novel cancer therapies.
AB  - Research over the last two years has explored a number of possible approaches to
      applying dendritic cell immunotherapy to the treatment of human cancers. The
      chosen strategy in clinical situations will vary for individual patients and will
      depend on the type of tumour, availability of tissue samples and potential source
      of dendritic cells. We believe that the isolation of fractionated tumour peptide
      from individual patients' tumours for use with autologous stem cell-derived
      dendritic cells may provide, in at least some cases, an effective and practical
      approach to cancer immunotherapy. This approach will provide a 'closed' system of
      tumour immunotherapy with all components (dendritic cells, antigen and cytotoxic
      T lymphocytes) being provided by the patient and applied in a tailor-made fashion
      to individual patients as an adjuvant to current anti-tumour therapies.

PMID- 9594967
TI  - Physical inactivity in New Zealanders aged 60 years and older.
AB  - AIMS: To determine the prevalence of physical inactivity among older New
      Zealanders (> or = 60 years) and to examine the patterns of physical inactivity
      by sex, age, residential and cognitive status. METHODS: Information on housework
      related and leisure-time physical activities obtained from the 910 controls in
      the Auckland Hip Fracture Study, was used to determine the prevalence of
      inactivity. Direct standardisation was used to extrapolate the inactivity
      prevalence figures from the study population to the general Auckland population.
      Logistic regression analyses were undertaken to examine the patterns of physical
      inactivity by sex, age, residential and cognitive status. RESULTS: Of the study
      participants 48.7% did not undertake any leisure-time physical activities and
      15.6% did not undertake any physical activity. Extrapolation of these data to the
      Auckland population indicated that 38.9% of older people do not participate in
      any leisure time activity and 6.1% do not partake in any physical activity. Non
      participation in physical activities was shown to be greater for women (odds
      ratio = 1.92; 95% confidence interval: 0.98-4.07); those in the older age groups
      (> or = 90 years, 7.00; 1.88-45.60); those living in institutions (6.52; 4.01
      10.64); and for those who were cognitively impaired (13.96; 7.06-28.92).
      CONCLUSION: Policies and programmes should focus on encouraging and supporting
      older people to become physically more active, by engaging in activities in which
      they enjoy participating; by educating older people as to the feasibility and
      benefits of physical activities, including maintenance of an independent active
      life; and by encouraging residents in institutions to continue their involvement
      in housework-related activities, such as gardening, home maintenance and general
      housework.

PMID- 9594968
TI  - Changes in CME uptake caused by reaccreditation.
AB  - AIM: To determine whether the requirements of the reaccreditation programme of
      the Royal New Zealand College of General Practitioners (RNZCGP) have changed the
      amount and type of continuing medical education (CME) done by the participating
      general practitioners. METHOD: A written questionnaire was sent to 200 randomly
      selected general practitioners doing the RNZCGP reaccreditation programme.
      RESULTS: The response rate was 82%. Although almost half the general
      practitioners had been motivated to spend more time on CME by the reaccreditation
      programme, for most this was a small increase. However, there was a trend towards
      selection of higher quality courses and towards increasing the time spent on
      educational activities more likely to result in changed behaviour. CONCLUSION:
      The RNZCGP reaccreditation programme is having beneficial effects on the CME
      activities of many of the participating general practitioners.

PMID- 9594969
TI  - Chronic hepatitis B virus infection in south Auckland.
AB  - AIM: Previous studies have identified high prevalence rates of hepatitis B
      infection in New Zealand Maori, Pacific Island and Asian populations within New
      Zealand. However, the true impact of chronic hepatitis B virus (HBV) infection on
      health resources has not been evaluated. This study was designed to determine the
      incidence of serious sequelae of chronic HBV infection in a high prevalence
      community. METHODS: All patients treated for HBV-related conditions at Middlemore
      Hospital from January 1995 to January 1997 were identified through discharge
      coding and laboratory records. Demographic characteristics and laboratory
      results, including liver function tests, hepatitis serology and liver histology
      were recorded. Number of admissions, average length of stay and survival were
      calculated from Casemix data. RESULTS: During the study period, 215 patients were
      referred for management of hepatitis B infection, of whom 179 had persistently
      elevated aminotransferases. Forty six percent of patients were hepatitis B 'e'
      antigen (HBeAg) negative, and 21% of these had delta co-infection (all Samoan).
      Liver biopsy was performed in 87 patients with raised aminotransferases. No
      features of chronic hepatitis were found in 5%, mild chronic hepatitis in 30%,
      moderate to severe chronic hepatitis in 44% and cirrhosis in 22%. Fifty five
      patients were admitted to hospital during the two year period with an HBV-related
      diagnosis, with an average length of stay of 12.2 days compared to 4.9 days for
      all other medical and surgical admissions during this period (p < 0.001). Twenty
      eight of the 55 subsequently died, 20 from hepatocellular carcinoma. CONCLUSIONS:
      Chronic hepatitis B infection is associated with significant morbidity and
      mortality in Maori, Pacific Islanders and Asians living in South Auckland.
      Screening of these high risk populations with vaccination of noninfected
      individuals should reduce the incidence of these serious sequelae and eventually
      lead to eradication of HBV.

PMID- 9594970
TI  - Professional help sought for emotional problems: coping with child sexual abuse
      in a Dunedin community sample of women.
AB  - AIM: To investigate how often women reporting child sexual abuse obtain
      professional help for emotional reasons compared with non-abused women and how
      useful they find it. METHOD: In a follow-up survey of a random community sample
      of women, information on formal help for emotional problems was analysed by
      demographic, health status and abuse information. RESULTS: In the year prior to
      survey, 11.8% of women in this community sample sought professional help for
      emotional problems. Women in the child sexual abuse sub-sample were significantly
      more likely than the comparison sub-sample to have sought help (16.6% vs 7.3%)
      but marital status (separation) was a more significant predictor. Problematic
      relationships or depression were the reasons given most often for help-seeking.
      Therapists/counsellors and general practitioners were the health professionals
      most often approached. Most help-seekers thought the help useful but some child
      sexual abuse help-seekers did not. The child sexual abuse sub-sample were more
      likely to report cost as a barrier. CONCLUSIONS: Relationship difficulties and
      depression are the most common reasons for seeking professional help for
      emotional problems. Women giving a history of child sexual abuse have higher
      rates of formal help-seeking and are more likely than other women to report that
      help they receive is not useful.

PMID- 9594971
TI  - The epidemiology of deliberate self poisoning presenting to Christchurch Hospital
      Emergency Department.
AB  - AIM: To review the recent epidemiology of deliberate self poisoning presentations
      to Christchurch Emergency Department and to compare this with 1992 and 1989 data.
      METHOD: A retrospective analysis of case and computer records over the twelve
      month period of 1996 was conducted and compared with published data for 1992 and
      1989. RESULTS: There were 713 presentations in 1996 to Christchurch Emergency
      Department with deliberate self poisoning, representing 1.1% (compared with 1.2%
      1992; 0.96% 1989) of total presentations. The female to male ratio was 1.9:1.0
      (compared with 1.5:1.0, 2.1:1.0). 70.1% of patients presenting were under the age
      of 35. The principal drugs ingested were antidepressants 20% (compared with
      24.4%; 15.7%) paracetamol (16.7% compared with 16.9%; 10.6%)
      hypnotics/anxiolytics 15.6% (benzodiazepines 11.0% compared with 23.6%; 18.0%),
      antipsychotics 10.7% (compared with 16.1%; not reported). Gastric decontamination
      was given to 61% (compared with 73% 1992), charcoal alone used in 54% (compared
      with 46%; 0.4%), gastric lavage and charcoal 7% (compared with 27%; 78%). 39%
      received no gastrointestinal decontamination (compared with 27% 1992). Of the
      patients presenting, 68.9% were admitted (compared with 59%; 66%), 10.2% to
      Intensive Care Unit (compared with 11%; 18%). There were 6 deaths (compared with
      2; 2). CONCLUSION: Deliberate self poisoning remains a problem mainly of the
      young with a gender ratio favouring female. Antidepressant medications,
      paracetamol, benzodiazepines and antipsychotics remain the most common classes of
      drugs taken alone or in combination. An important trend within the
      antidepressants is the increasing misuse of selective serotonin reuptake
      inhibitors. Rates of admission to hospital and the Intensive Care Unit have
      changed but mortality rates have had no significant change over the three time
      periods. Gastrointestinal decontamination techniques employed follow a trend
      towards the use of activated charcoal and away from gastric lavage.

PMID- 9594972
TI  - Anaemia in Maori infants.

PMID- 9594973
TI  - Product recall.

PMID- 9594974
TI  - Children and tobacco imagery on New Zealand television.

PMID- 9594975
TI  - Fibrinolytic activation with intrauterine fetal death.

PMID- 9594976
TI  - First report of potentially zoonotic tuberculosis in fur seals in New Zealand.

PMID- 9594977
TI  - Mix and match for tobacco control.

PMID- 9594978
TI  - The cloning of Dolly: dare humankind copy?

PMID- 9594980
TI  - The gynaecologist who started all the fuss.

PMID- 9594981
TI  - No place of safety.

PMID- 9594982
TI  - Preventing perinatal HIV transmission in developing countries--do we know enough?

PMID- 9594983
TI  - Preventing perinatal HIV transmission--now is the time to act!

PMID- 9594984
TI  - Should South Africa be preparing for interventions to reduce mother-to-infant
      transmission of HIV-1?

PMID- 9594985
TI  - The avalanche of children requiring social services in the Western Cape.

PMID- 9594986
TI  - Severe head injury in children--a preventable but forgotten epidemic.
AB  - OBJECTIVE: To determine the outcome of seriously head-injured children and to
      analyse the factors that affect their prognosis. DESIGN: A retrospective analysis
      of all severely head-injured children treated between 1990 and 1993. SETTING: Red
      Cross War Memorial Children's Hospital's trauma unit and neurosurgery service.
      PATIENTS: One hundred and two children under the age of 14 years with admission
      Glasgow Coma Scores (GCSs) of below 8. RESULTS: There were 57 boys and 45 girls.
      The average time of assessment after injury was 2.8 hours. Eighty-three injuries
      were caused by pedestrian motor vehicle accidents. Thirty-seven were associated
      with other serious organ system injuries. Fifty-eight children died and only 36
      made a good recovery. All children with a GCS of 3-4 died. Factors that were
      particularly associated with a poor prognosis were: (i) age less than 3 years;
      (ii) associated extracranial injury; (iii) GCS 3-4 following resuscitation; and
      (iv) diffuse cerebral swelling on computed tomography. CONCLUSION: Pedestrian
      motor vehicle accidents are the most common cause of serious paediatric head
      injury in the Cape Town area. Children with a presenting coma score of less than
      8 have an extremely high mortality and morbidity rate, despite modern intensive
      care. Preventive strategies are essential.

PMID- 9594987
TI  - Gunshot injuries in infants and children in KwaZulu-Natal--an emerging epidemic?
AB  - OBJECTIVES: To determine the pattern of firearm injuries in children under the
      age of 13 years admitted to a paediatric surgical unit in KwaZulu-Natal and to
      assess the impact of such injuries on hospital resources. DESIGN: Retrospective
      review of the Department of Paediatric Surgery and hospital databases for all
      gunshot admissions, 1983-1995 inclusive. SETTING: King Edward VIII Hospital,
      Durban. SUBJECTS: Children aged 12 years and under admitted to the care of the
      Department of Paediatric Surgery for management of gunshot injuries. METHODS:
      Data retrieved included demographic details, circumstances of injury, duration of
      hospital stay, management and outcome in terms of mortality and long-term
      morbidity. RESULTS: One hundred and six patients were identified, of whom 96 were
      available for review. There has been a rapid escalation of numbers presenting.
      During 1994-1995, an additional 38 children with gunshot injuries were admitted
      to other units within Durban academic hospitals. The mean age of injury in
      patients admitted to the Department of Paediatric Surgery was 6.4 years and the
      abdomen was the most frequently injured area. Multiple injuries were common. The
      in-hospital mortality rate was 10.4%. Major morbidity, including paraplegia,
      hemiplegia, amputation and major peripheral nerve deficit, was seen in 11.4%.
      Duration of bed occupancy in the general surgical ward reached 247 days in 1995.
      CONCLUSION: There is an increasing incidence of gunshot injuries in this region.
      Of children surviving to reach hospital, 10% die and 11% are left with lifelong
      major morbidity. Most victims are innocent bystanders and too young to be
      considered active participants. Prevention will require sociopolitical stability
      and the disarming of the community.

PMID- 9594989
TI  - The influence of South African mineral water on reduction of risk of calcium
      oxalate kidney stone formation.
AB  - OBJECTIVES: This study was undertaken to identify a South African mineral water
      containing relatively high concentrations of calcium and magnesium and to
      investigate its effect on urinary biochemical and physicochemical risk factors
      associated with calcium oxalate kidney stone formation. DESIGN: The study
      followed a change-over design in which each subject followed a randomised
      sequence of three water-drinking protocols involving their normal diet, a calcium
      and magnesium-rich mineral water and a mineral water deficient in these elements.
      SETTING: University of Cape Town. SUBJECTS: 54 volunteers without any previous
      history of stone disease (27 men, 27 women) in the age group 21-35 years and 31
      with a history of calcium oxalate kidney stones (24 men, 7 women) in the age
      group 25-45 years participated in the study. OUTCOME MEASURES: Both mineral
      waters favourably altered several risk factors. However, the effect of the
      calcium- and magnesium-rich water was shown to be significantly greater as it
      altered a larger number of these factors and induced several unique changes that
      were not achieved by the other water. CONCLUSIONS: The risk of calcium oxalate
      stone formation can be significantly reduced by consumption of mineral water
      which is rich in calcium and magnesium.

PMID- 9594990
TI  - Do stroke patients realise that a consequence of hypertension is stroke?
AB  - STUDY OBJECTIVE: The specific objectives of the study were to survey residual
      disability and handicap following stroke. Information on four risk factors,
      namely hypertension, age, smoking, and alcohol abuse, was obtained. Enquiry was
      made into the subjects' insight into the causes of their problems. DESIGN:
      Descriptive survey. SETTING: Baragwanath Hospital and Soweto. PARTICIPANTS:
      Stroke patients 12-14 weeks post-discharge. OUTCOME MEASURES: Structured
      questionnaire. RESULTS: A total of 361 patients were initially screened. Only 54
      fulfilled all inclusion criteria, 38 (70%) over 50 years of age and 16 (30%)
      under 50 years. Ninety-three of the 361 died within the first 3 months; 71% of
      all patients knew that they had suffered a stroke. Only 20% of the total group
      understood that hypertension had probably caused their stroke, although 76% of
      the older group and 56% of the younger group had been told at some stage that
      they were hypertensive. Of the older group 32% knew the name of their medication,
      21% could not name their medication and 23% claimed they were on no medication.
      Similarly in the younger group, 19% could name their medication, 25% could not
      name their medication, and 12% were on no medication. In addition 16% of the
      older group and 56% of the younger group admitted to smoking. The abuse of
      alcohol in both groups was low, but this figure was taken from subjective
      assessment and may not reflect the true extent of drinking as a risk factor.
      CONCLUSION: Most patients in this study appear well aware of their hypertension
      and take medication. However, they seem unaware that their hypertension and
      stroke are causally linked and their hypertension knowledge is suboptimal. It is
      also apparent that smoking is increasing as a major risk factor for stroke in the
      black population of South Africa. Patients need more education regarding
      hypertension and its consequences.

PMID- 9594992
TI  - Angiotensin receptor blockers and pregnancy.

PMID- 9594991
TI  - Paediatric AIDS--is now not the right time to act?

PMID- 9594993
TI  - Use of drips in children.

PMID- 9594994
TI  - Serious adverse reactions in neonates receiving intravenous electrolyte solutions
      -a call for reports.

PMID- 9594995
TI  - Antifolate-resistant malaria infections in Mpumalanga.

PMID- 9594996
TI  - Toothless children.

PMID- 9594997
TI  - Vaginal insertion and douching practices among sex workers at truck stops in
      KwaZulu-Natal.

PMID- 9594998
TI  - Schistosomiasis surveillance associated with the Lesotho Highlands Water Project.

PMID- 9594999
TI  - Antithrombotic therapy for myocardial infarction.

PMID- 9595001
TI  - Which patients should receive an ACE inhibitor after acute myocardial infarction?

PMID- 9595000
TI  - Urinary levels of tissue kallikrein in black and Indian hypertensives and their
      implications for therapy.
AB  - It is accepted that blacks differ from white and Indian hypertensives in their
      response to hypotensive agents. Black hypertensives in the USA have lower urinary
      tissue kallikrein (TK) excretion levels than white hypertensives. It has been
      suggested that blacks respond better to thiazide diuretics than to beta-blockers
      because thiazides increase TK excretion whereas beta-blockers decrease it. This
      study compares the excretion of urinary TK in black and Indian hypertensive and
      normotensive subjects. Urinary TK levels were measured with the selective,
      synthetic peptic substrate with the sequence of H-D-Val-Leu-Arg-pNA. Ten
      hypertensive patients on placebo therapy and 10 normotensive black and Indian
      subjects provided 3 samples at weeks 0, 2 and 4 for the determination of urinary
      TK. The results were analysed and analysis of variance was used to compare the
      two racial groups. There were no significant differences in urinary TK values of
      the three biweekly individual samples. Urinary TK values (ng TK/microgram
      protein) in Indian hypertensives were generally lower than in black
      hypertensives.

PMID- 9595002
TI  - Cardiac tamponade following umbilical vein catheterisation in a neonate.
AB  - Umbilical vein catheterisation (UVC) should not routinely be used in the neonatal
      intensive care unit, and when it is used special precautions should be taken and
      guidelines followed. We present an unusual complication which occurred following
      use of an umbilical vein catheter in a term neonate. This case highlights another
      potentially lethal complication of UVC, and emphasises the risks associated with
      the procedure. In order for the benefits of UVC to outweigh the risks, certain
      guidelines are reviewed. The importance of confirming the position of the
      catheter tip with both anteroposterior and lateral radiographs is emphasised.

PMID- 9595003
TI  - Aortocoronary saphenous vein bypass aneurysm--an unusual presentation.
AB  - Aneurysms of aortocoronary saphenous bypass grafts are an unusual and rare
      complication of coronary artery bypass surgery. Approximately 30 such cases have
      been reported in the literature. Atheromatous aneurysms usually appear late (more
      than 10 years after grafting). They are usually asymptomatic, but may manifest
      for investigation as a lesion altering the mediastinal contour. We report a
      further case of an atherosclerotic aortocoronary saphenous vein graft aneurysm in
      which the patient presented with angina due to aneurysmal compression of the host
      vessel.

PMID- 9595004
TI  - Effects of halothane on post-cardioplegic functional recovery--the role of
      cardioplegic solution.

PMID- 9595005
TI  - Coronary stenting 1997.

PMID- 9595006
TI  - Antithrombotic therapy for myocardial infarction--Part I.

PMID- 9595011
TI  - Congestive heart failure--can we really expect further advances in drug
      management?

PMID- 9595012
TI  - The "safe" blood donor and the national blood supply: is there a new interface?

PMID- 9595013
TI  - Effective removal of copper by plasma exchange in fulminant Wilson's disease.
AB  - BACKGROUND: Patients who present with fulminant hepatic failure due to Wilson's
      disease may develop hemolytic anemia and renal insufficiency. In this entity,
      acute hepatocellular necrosis triggers the release of copper ions into the
      circulation, which leads to toxic effects on red cell metabolic pathways and
      hemolysis. STUDY DESIGN AND METHODS: The utility of therapeutic plasma exchange
      to rapidly remove copper and reduce toxic serum copper levels was studied in two
      patients with fulminant Wilson's disease. RESULTS: Intensive plasma exchange
      using fresh-frozen plasma replacement removed substantial amounts of copper from
      the hypercupremic patients, resulting in a rapid reduction in serum copper levels
      and decreased hemolysis. The net copper removal was proportional to the serum
      level, ranging from 7,000 to 11,800 micrograms per procedure in one patient and
      from 3,700 to 6,800 micrograms in the other. CONCLUSION: Plasma exchange allows a
      rapid reduction in elevated serum copper levels in patients with fulminant
      Wilson's disease. This leads to an amelioration of hemolytic anemia and provides
      clinical stabilization until liver transplantation can be performed.

PMID- 9595014
TI  - Hemagglutination inhibition of Cromer blood group antibodies with soluble
      recombinant decay-accelerating factor.
AB  - BACKGROUND: Cromer blood group antigens are located on decay-accelerating factor
      (DAF, CD55), which contains four short consensus repeats (SCRs). Cromer system
      antibodies may be of clinical significance in blood transfusion. STUDY DESIGN AND
      METHODS: Soluble recombinant DAF (srDAF) constructs, consisting of all four SCRs
      or of only two SCRs, were expressed in the yeast Pichia pastoris. They are used
      in hemagglutination-inhibition tests with Cromer system antibodies and with DAF
      specific monoclonal antibodies. RESULTS: The srDAF inhibited hemagglutination by
      all Cromer system alloantibodies in undiluted serum. Antibodies to antigens of
      other blood group systems were not inhibited by the srDAF. Hemagglutination
      inhibition tests with domain-deleted srDAF showed that UMC is on SCR-4 and
      confirmed that Tca, TcaTcb, and WESb are on SCR-1; Dra is on SCR-3; and Cra is on
      SCR-4. CONCLUSIONS: Hemagglutination inhibition with srDAF is useful in the
      recognition of antibodies that belong to the Cromer blood group system and
      facilitates pretransfusion testing. This use of domain-deleted srDAF provides an
      easy method of determining epitope location on DAF and is an aid to more precise
      identification of Cromer system antibodies.

PMID- 9595015
TI  - Investigation of the survival of paroxysmal nocturnal hemoglobinuria red cells
      through the immunophenotyping of reticulocytes.
AB  - BACKGROUND: Complement-mediated lysis of red cells (RBCs) is a classic feature of
      paroxysmal nocturnal hemoglobinuria (PNH) that is traditionally studied with a
      combination of radiolabeling of RBCs and in vitro hemolysis tests. Phenotyping of
      reticulocytes was used as an alternative method for the evaluation of the
      relative life span of normal RBCs (PNH I) and RBCs that were partially (PNH II)
      or completely (PNH III) deficient in CD59. STUDY DESIGN AND METHODS: Murine
      monoclonal antibodies CD55, CD58, and CD59 and thiazole orange were used to
      phenotype reticulocytes by two-color flow cytometry in nine PNH patients. RBC
      survival could be calculated from the ratio of CD59- or CD59low mature RBCs to
      CD59- or CD59low reticulocytes obtained from these patients who had not received
      a transfusion. RESULTS: The life span of PNH III RBCs varied from about 17 to 60
      days. PNH II reticulocytes were found in the four patients with PNH II RBCs. The
      life span of PNH II RBCs varied with their residual expression of CD59, and cells
      with 15 to 20 percent of the normal amount of CD59 were protected against in vivo
      hemolysis. CONCLUSION: Phenotyping of reticulocytes is a convenient and reliable
      tool for evaluating the relative survival of normal and PNH RBCs. PNH II and PNH
      III reticulocytes are phenotypically distinct, and some PNH II RBCs may be
      sensitive to complement-mediated lysis in vitro, but normally they are complement
      resistant in vivo.

PMID- 9595016
TI  - Survey on pretransfusion testing.
AB  - BACKGROUND: Hospitals and blood centers throughout the United States use a
      variety of reagents and methods to perform pretransfusion testing. A survey was
      developed to determine the reagents and methods in use and their relative
      prevalence in different work settings. STUDY DESIGN AND METHODS: A national
      survey on pretransfusion testing was conducted. Surveys were distributed to state
      and regional blood bank associations, which then distributed them to hospitals
      and blood centers within their region. In most instances, the blood centers
      distributed the survey to the local hospitals. Completed surveys were returned to
      the authors for review, and all information was entered into a database for
      analysis. RESULTS: Analysis of the data shows that the majority of blood banks
      use monoclonal reagents for ABO testing and monoclonal-polyclonal blended
      reagents for Rh testing. The data show that anti-IgG and polyclonal antihuman
      globulin reagents are used almost equally for antibody screening (detection)
      tests and that most blood banks use a three-cell antibody-screening test.
      Slightly more than 50 percent of hospitals use an immediate-spin crossmatch in
      the absence of unexpected antibodies. CONCLUSION: A number of approved reagents
      and methods are used by blood bank laboratories for pretransfusion testing.
      Facility size (number of beds) and type tend to influence the choice of methods
      and reagents employed. This survey provides an opportunity for blood bank
      laboratories to compare their current practices with those of their peers.

PMID- 9595017
TI  - Demographic characteristics, unreported risk behaviors, and the prevalence and
      incidence of viral infections: a comparison of apheresis and whole-blood donors.
      The Retrovirus Epidemiology Donor Study.
AB  - BACKGROUND: The demographics, deferrable risk behaviors, and the prevalence and
      incidence of viral infections of apheresis (PH) and whole-blood (WB) donors were
      compared, to characterize these two populations and to evaluate the relative
      safety of PH and WB donors in terms of transfusion-transmitted viral infections.
      STUDY DESIGN AND METHODS: A comparison was made of 36,119 PH donors (> or = 1 PH
      donation) and 1.38 million WB donors (> or = 1 WB donation) in terms of
      demographics and the prevalence (/100,000 donors) and incidence (/100,000 person
      years) of viral infections, by using data collected at five United States blood
      collection centers between 1991 and 1994. Deferrable risk behaviors were defined
      as those risk behaviors that would have resulted in donor deferral, had they been
      reported. The prevalence of deferrable risk behaviors was estimated by using data
      collected through an anonymous mail survey. RESULTS: PH donors were older and
      more likely than repeat (2+ donations) WB donors to be female, white, and United
      States-born and to have a higher degree of education (p < or = 0.001). The
      prevalence of any viral infection was 50 percent higher in WB donors than in PH
      donors (p = 0.04), whereas the incidence of HIV, human T-lymphotropic virus, and
      hepatitis B surface antigen was nonsignificantly higher in WB donors. The
      prevalence of deferrable risk behaviors did not differ in the two groups.
      CONCLUSION: Further studies will be needed to evaluate whether the difference in
      the prevalence of viral infections observed in this study can be explained by
      demographic characteristics and patterns of donation frequency.

PMID- 9595018
TI  - Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study.
AB  - BACKGROUND: There are obvious advantages to increasing donor retention. However,
      for reasons of blood safety, certain donors may, in fact, be more desirable to
      retain than others. "Safe" donors are defined as those who provided a blood
      donation that was negative on all laboratory screening tests and who subsequently
      reported no behavioral risks in response to an anonymous survey. This study
      identifies the most important factors affecting the intention of "safe" donors to
      provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking
      about donation history, sexual history, injecting drug use, and recent donation
      experience was mailed to 50,162 randomly selected allogeneic donors (including
      directed donors) who gave blood from April through July or from October through
      December 1993 at one of the five United States blood centers participating in the
      Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to
      designate donors with nonreactive laboratory screening tests at their most recent
      donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially
      higher response among repeat donors. According to reported intentions only, the
      vast majority of "safe" donors indicated a high likelihood of donating again
      within the next 12 months. Only 3.4 percent reported a low likelihood of donating
      again. A comparison of those likely to return and those unlikely to return
      reveals significant differences in demographics and in ratings of the donation
      experience. A higher proportion of those unlikely to return were first-time
      donors, minority-group donors, and donors with less education. The highest
      projected loss among "safe" donors was seen for those who gave a fair to poor
      assessment of their treatment by blood center staff or of their physical well
      being during or after donating. CONCLUSION: These data suggest that efforts to
      improve donors' perceptions of their donation experience, as well as attention to
      the physical effects of blood donation, may aid in the retention of both repeat
      and first-time donors.

PMID- 9595019
TI  - Structuring a safer donor-replacement program.
AB  - BACKGROUND: Replacement donors are more likely than volunteer donors to have
      positive or abnormal tests for transfusion-transmissible disease. In an effort to
      increase the donor pool, workers sought to identify a safer replacement-donor
      subgroup that may be acceptable for routine donations. STUDY DESIGN AND METHODS:
      In a retrospective review and cohort study, the replacement-donor effect was
      separated from the new-donor effect. The relative effect the replacement donor
      has on the risk of transfusion-transmissible diseases, donor retention, and
      frequency of returning donations was then quantified by comparison against the
      effect of repeat volunteer donors. RESULTS: The replacement donor had 3.1 times
      the risk and 0.72 times the donor retention rate and made 0.81 times as many
      returning donations as the repeat volunteer donor. The figures for the new-donor
      effect were similar. The two risks were additive, making a new replacement donor
      particularly hazardous. If replacement donations only from repeat replacement
      donors were considered, the donor risk and the number of donations per returning
      donor were made comparable to those for the general (combined) volunteer donor.
      CONCLUSION: The negative effect of the replacement donor is similar in magnitude
      to that of the new volunteer donor. A replacement-donation program targeting
      repeat replacement donors has an acceptable risk profile and may be a valuable
      adjunct to the collection of blood from general volunteer donors.

PMID- 9595020
TI  - An acute hemolytic transfusion reaction caused by an anti-P1 that reacted at 37
      degrees C.
AB  - BACKGROUND: Hemolytic transfusion reactions (HTRs) due to anti-P1 have rarely
      been reported. There is only one report (from 1945) of an acute HTR due to anti
      P1. CASE REPORT: A 74-year-old woman with anti-P1 was given blood that had been
      found to be compatible by the use of prewarmed serum and saline-suspended red
      cells (RBCs) and of an antiglobulin test with anti-IgG. The test mixtures were
      not centrifuged or inspected for agglutination after the 37 degrees C incubation
      phase. After transfusion of 50 mL of P1 + blood, the patient had an acute HTR
      (hemoglobinemia, hemoglobinuria, and increased blood pressure, temperature, and
      respiration). RESULTS: When studied by a reference laboratory, the anti-P1 was
      shown to be easily detectable (3+ agglutination) by a prewarming technique
      (saline or low-ionic-strength saline [LISS]), which included centrifugation at 37
      degrees C, but only weak reactions were observed when centrifugation after 37
      degrees C incubation was omitted. The indirect antiglobulin test was weakly
      positive (1+) with anti-IgG, but polyspecific anti-human globulin reacted 2+. The
      anti-P1 agglutinin was IgM, and its titer was 16 at 37 degrees C (prewarmed) and
      256 at 23 degrees C; it caused hemolysis of RBCs at 37 degrees C under conditions
      known to enhance hemolysis. An indirect monocyte monolayer assay gave results of
      11.2 and 22 percent in testing of P1 + RBCs incubated with the patient's serum
      alone and with patient's serum plus fresh normal serum (as a source of
      complement), respectively (normal < or = 3%). CONCLUSION: An acute HTR was caused
      by a hemolytic anti-P1 that reacted at 37 degrees C. This antibody was not
      detected by the hospital in a prewarmed crossmatch that omitted 1) the addition
      of LISS, 2) the reading for agglutination after the 37 degrees C incubation, and
      3) the use of antiglobulin sera containing anti-complement.

PMID- 9595021
TI  - Hepatitis C virus and GB virus C/hepatitis G virus viremia in Swedish blood
      donors with different alanine aminotransferase levels.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a known blood-borne hepatotropic virus for
      which antibody screening of blood donors is universally practiced. The newly
      identified GB virus C (GBV-C) and its strain variant hepatitis G virus (HGV) are
      of unknown pathogenic significance, and screening of blood donors for this agent
      has not yet been implemented. Polymerase chain reaction (PCR) is the most
      sensitive method for detecting HCV viremia and is the only method presently
      available for the diagnosis of GBV-C/HGV infection. STUDY DESIGN AND METHODS: RNA
      extracts of sera from 577 anti-HCV-negative blood donors (393 with elevated
      alanine aminotransferase [ALT] levels, 184 with normal ALT levels) were tested
      with nested PCR for HCV and GBV-C/HGV directed at the 5'-noncoding regions of the
      two viruses. RESULTS: One donor with elevated ALT was HCV PCR positive. This
      donor was anti-HCV negative when recruited to the study but subsequently
      developed anti-HCV. Of the 19 donors with GBV-C/HGV viremia in the series as a
      whole, 16 belonged to the group with elevated ALT levels and 3 to the group with
      normal ALT levels; the group difference in prevalence was nonsignificant (4.1%
      [16/393] vs. 1.6% [3/184; p = 0.20]). Phylogenetic analysis showed 16 of the GBV
      C/HGV isolates to be classifiable as subtype 2a and three as subtype 2b. At
      follow-up 3 to 5 years later, 11 of 18 donors were still viremic. CONCLUSION:
      There was no significant difference in GBV-C/HGV viremia in the group with
      elevated ALT levels and the group with normal ALT levels. The frequency and
      subtype distribution in the present series were similar to those in other Western
      countries.

PMID- 9595022
TI  - Minimal number of circulating CD34+ cells to ensure successful leukapheresis and
      engraftment in autologous peripheral blood progenitor cell transplantation.
AB  - BACKGROUND: The number of peripheral blood (PB) CD34+ cells has been widely used
      to monitor the timing of leukapheresis for autologous transplantation. However,
      no cutoff value for CD34+ cells in PB has been defined as a guideline for the
      identification of patients in whom the harvest would be effective and those in
      whom there was a high probability of failure. STUDY DESIGN AND METHODS: The
      present study investigated the best threshold of CD34+ cells in PB for successful
      harvesting and engraftment, using 263 PB samples with their corresponding
      leukapheresis components. In addition, that measure has been compared to other
      commonly used criteria such as the white cell count, the number of mononuclear
      cells, and the number of colony-forming units-granulocyte macrophage in PB.
      RESULTS: Time to engraftment of both granulocytes and platelets was significantly
      influenced by the number of CD34+ cells transfused, but all patients receiving >
      or = 0.75 x 10(6) CD34+ cells per kg achieved engraftment within a reasonable
      number of days (> 0.5 x 10(9)/L granulocytes by Day 11 and > 20 x 10(9)/L
      platelets by Day 13). A clear correlation between the number of CD34+ cells per
      microL in PB and of CD34+ cells per kg collected was found at each apheresis (r =
      0.9, p < 0.0001). Moreover, the number of CD34+ cells per microL measured in PB
      the day the first leukapheresis was initiated displayed an excellent correlation
      with the total amount of CD34+ cells per kg finally collected (r = 0.81, p <
      0.0001). On the basis of the regression curve obtained and the clinical
      engraftment results, it was found that the presence of > 5 CD34+ cells per microL
      in PB ensured a good yield from the harvest in 95 percent of patients and would
      avoid an unsuccessful harvest in 81 percent of cases. CONCLUSION: A dose of only
      0.75 x 10(6) CD34+ cells per kg guarantees hematopoietic recovery within a
      reasonable number of days. To initiate a leukapheresis from which enough
      progenitor cells may confidently be obtained, a minimum of 5 CD34+ cells per
      microL in PB is required.

PMID- 9595023
TI  - Gender-related variation in transfusion practices.

PMID- 9595024
TI  - An annotated bibliography on autologous transfusion: second edition.

PMID- 9595025
TI  - Hypotensive reactions during platelet transfusions.

PMID- 9595026
TI  - Hypotensive reactions to red cells filtered at the bedside, but not to those
      filtered before storage, in patients taking ACE inhibitors.

PMID- 9595028
TI  - Hypotensive reactions associated with white cell-reduced apheresis platelet
      concentrates in patients not receiving ACE Inhibitors.

PMID- 9595027
TI  - Hypotensive reactions with a white cell-reduction filter: activation of
      kallikrein-kinin cascade in a patient.

PMID- 9595029
TI  - Elevated alanine aminotransferase in Brazilian blood donors.

PMID- 9595030
TI  - Transfusion safety: realigning efforts with risks.

PMID- 9595031
TI  - Retinyl substituted-benzyl ethers. Inhibition of mammary carcinogenesis by
      retinyl 3,4,5-trimethoxybenzyl ether (RTMBE).
AB  - Recently, we reported that retinyl 2-propynyl ether (RPE) inhibits MNU-induced
      mammary cancer in rats and is less toxic than RME and retinyl acetate. The
      preparation and biological investigations of retinyl ethers have now been
      extended to retinyl substituted-benzyl ethers, some of which bind to cellular
      retinol-binding protein. In long-term (160-180 days) experiments, retinyl 3,4,5
      trimethoxybenzyl ether (RTMBE) has been shown to be active against MNU-induced
      mammary cancer in Sprague-Dawley rats. In effectiveness, RTMBE is comparable, at
      least, to retinyl acetate; but, unlike retinyl acetate, RTMBE is comparatively
      non-toxic to rats and mice, is not converted enzymatically to retinol, and does
      not cause significant increases in retinyl palmitate concentrations in the liver.
      RTMBE reaches high concentrations in mammary tissue. Two of the four RTMBE
      congeners that were evaluated in 90 day studies were moderately effective in
      inhibiting mammary carcinogenesis.

PMID- 9595032
TI  - Antineoplastic agents 389. New syntheses of the combretastatin A-4 prodrug.
AB  - Combretastatin A-4 (1) as the phosphate ester prodrug (3d) is a potent
      antineoplastic and antiangiogenesis substance and is in advanced preclinical
      development. For the purpose of improving the phosphorylation synthetic sequence
      from combretastatin A-4, new routes were investigated. The phosphorylation step
      was found to be considerably improved using in situ-generated dibenzyl
      chlorophosphite. Cleavage of the benzyl esters employing a
      trimethylchlorosilane/sodium iodide procedure, followed by treatment with sodium
      methoxide, led to the water-soluble prodrug (3d) in high yield.

PMID- 9595033
TI  - Sequence-specific DNA alkylation of novel tallimustine derivatives.
AB  - Three different groups of analogs of the sequence-specific minor groove alkylator
      tallimustine (2) have been synthesized and investigated. Within group I, the
      dibromo nitrogen mustard (3) and the half-mustard (4) are more cytotoxic (IC50 =
      0.6 and 40 ng/ml respectively) than tallimustine (IC50 = 50.3 ng/ml) against
      L1210 cells with high reactivity against the region 5'-TTTTGA. The diol
      derivative (6) and the difluoro nitrogen mustard (5) were not cytotoxic against
      L1210 cells and did not show any detectable DNA alkylation. The two compounds
      modified in the propionamidine terminus (7 and 8, group II), showed lower
      cytotoxic potency (IC50 = 130 and 94 ng/ml respectively) against L1210 cells than
      tallimustine (IC50 = 50.3 ng/ml) and a loss of in vitro sequence specificity for
      DNA alkylation. Considering the compounds in which the pyrrole rings were
      replaced by one (9) or two (10) pyrazole rings, compound 9 was not significantly
      cytotoxic against L1210 cell line and was apparently unable to produce alkylation
      on the DNA fragments tested, while compound 10 showed decreased cytotoxicity
      (IC50 = 114 ng/ml) and no modification in the pattern and intensity of DNA
      alkylation. The data obtained in this work suggest that it is possible to
      increase tallimustine potency by modifying the nitrogen mustard moiety. Moreover,
      the sequence specificity of DNA alkylation appears to be affected by the
      modification of the propionamidino moiety but not by the isosteric modification
      of the pyrrole rings. The correlation between cytotoxicity and alkylation pattern
      suggests that tallimustine exerts its cytotoxicity through DNA sequence-specific
      alkylation of the adenine located in the sequence 5'-TTTTGA.

PMID- 9595034
TI  - Assessment of toxicity of bis-platinum complexes in hypoxic and aerobic cells.
AB  - There is considerable interest in the bis-platinum series of complexes as
      potential chemotherapeutic agents, due to their activity in cisplatin-resistant
      lines and in various tumor types. Our interest in their hypoxic selectivity stems
      from the fact that cisplatin exhibits greater cytotoxicity in hypoxic than
      aerobic cells. Unlike nitroaromatics, quinones, tirapazamine and many other
      hypoxia selective agents, a 'bioreductive' moiety cannot explain these
      observations. We hypothesized that DNA-protein cross-links (D-P) might play a
      role in the mechanism. Bis-platinum complexes have variable cross-linking
      potentials, and their toxicities were assessed in air or hypoxia in CHO cells. Of
      the three classes examined, only those from the 2,2/cis,cis series show greater
      hypoxic selectivity than cisplatin. These have greater potential for cross-links
      than cisplatin, being potentially bifunctional at each platinum, with the two
      leaving groups (X) in the cis position, and with variable distance (n) between
      the platinum centers: cis-[(PtX2(NH3))2H2N(CH2)nNH2]. Cellular platinum
      accumulation and DNA binding were also measured, and like cisplatin, results are
      consistent with a more toxic lesion formed in hypoxia. Lower hypoxic selectivity
      in the UV20 cell line may reflect an inability to excise the relevant lesion.
      These results support the D-P hypothesis. Further support comes from a
      1,1/trans,trans complex which does not form D-P and which exhibited the reverse
      behavior to 2,2/cis,cis or cisplatin, i.e. higher toxicity in aerobic than in
      hypoxic cells. This study examines the possibility of an additional mechanism of
      selection for hypoxic toxicity involving DNA-protein cross-links.

PMID- 9595035
TI  - Mono- and dysfunctional nitrogen mustard analogues of the DNA minor groove binder
      pibenzimol. Synthesis, cytotoxicity and interaction with DNA.
AB  - Two series of mono- and dysfunctional aniline mustards linked to a
      bisbenzimidazole minor groove binder have been prepared using a new method
      (polyphosphate ester-mediated direct coupling of appropriate mustard acids with a
      preformed advanced phenylenediamine intermediate). As the linker chain attaching
      the mustard was lengthened the binding site size of the compounds to calf thymus
      DNA remained essentially constant at 2.6 nucleotides, but reversible binding
      strength declined by a factor of 2. Analogues with longer linker chains alkylated
      DNA much more rapidly than those with shorter chains, consistent with the
      electronic factors. The short chain analogues also failed to alkylate a 120 bp
      HindIII to Bg/II fragment of the gpt gene, as measured by gel electrophoresis
      cleavage assays. The longer chain analogues (both mono- and dysfunctional
      mustards) showed patterns of DNA alkylation that varied with chain length. In
      particular, while most compounds showed substantial N7 alkylation at many guanine
      residues, the analogue with a (CH2)3 linker chain showed strong alkylation at
      adenine sites in poly-AT regions. For the longer chain analogues, the
      bifunctional mustards were substantially (10- to 20-fold) more cytotoxic than the
      corresponding monofunctional analogues.

PMID- 9595036
TI  - A novel germ-line mutation in the noncoding region of the p53 gene in a Li
      Fraumeni family.
AB  - We identified a novel germ-line p53 mutation in the noncoding, nonsplicing
      regions of a Li-Fraumeni family. Patients belonging to this family included
      pediatric medulloblastoma and rhabdomyosarcoma patients and a breast carcinoma
      patient. Three positions in the p53 gene were analyzed for loss of heterozygosity
      (LOH). One of the three loci retained heterozygosity, whereas the other two
      exhibited LOH. Sequence analysis of the third locus identified a change of 5'
      CCGGGTGA-3' to 5'-CCAGGTTGGA-3', 63 bp downstream of exon 6. The mutation was
      identified in the germ line of the two pediatric patients and in each of the
      related parents. We excluded any additional mutation in the entire coding region
      of the p53 gene, including splice-site intronic sequences. Strong positive
      nuclear staining of the p53 protein was detected in both normal and tumor
      paraffin-embedded tissues. Eighty-five normal persons were negative for this
      alteration, which thus supports it as a mutation. These results may indicate that
      genetic changes within the noncoding region of the p53 gene may serve as an
      alternative mechanism of activating this gene. Mutations in the noncoding region
      of this gene should be further studied.

PMID- 9595037
TI  - Cytogenetic and fluorescence in situ hybridization studies in a case of
      anaplastic thyroid carcinoma.
AB  - Cytogenetic analysis of a case of anaplastic thyroid carcinoma revealed multiple
      numerical and structural chromosomal changes, including a der(9)
      add(9)(p22)hsr(9)(p?). Fluorescence in situ hybridization (FISH) studies
      performed to identify the genetic nature of this derivative chromosome showed
      that both the additional material and the hsr region were composed of only
      chromosome 9 sequences and that the C-ABL oncogene was not one of the genes
      harbored at the hsr region. We suggest that amplification of gene(s) located at
      chromosome 9, other than the C-ABL, may play a significant role in anaplastic
      evolution of thyroid carcinomas.

PMID- 9595038
TI  - Askin tumor and acute myeloid leukemia in a patient with constitutional partial Y
      disomy.
AB  - We report the case of a young adult male carrying a constitutional unbalanced
      t(Y;13)(q11-12;p13) leading to a partial Y disomy, and presenting successively,
      in a 39-month interval, with an Askin tumor and a t(8;21) acute myeloid leukemia.
      The origin of the two neoplasias in this patient is discussed.

PMID- 9595039
TI  - Translocation (3;5)(q21;q34) in erythroleukemia: a molecular and in situ
      hybridization study.
AB  - Translocation (3;5) is an uncommon karyotypic aberration in acute myeloid
      leukemia (AML). With the exception of M3, t(3;5) has been reported in every other
      subtype of AML, being most frequently associated with AML M6. Although a variety
      of breakpoints have been described, it has been suggested that the breakpoints in
      t(3;5) of all the reported cases should be assigned to 3q25.1 and 5q34. Recently,
      the breakpoints in three pediatric cases of AML M2 with t(3;5) were cloned and
      shown to involve the myelodysplasia/myeloid leukemia factor I (MLF1) gene on
      3q25.1 and the nucleophosmin (NPM) gene on 5q34, generating a chimeric NPM/MLF1
      transcript. An adult case of indolent erythroleukemia was found on karyotypic
      analysis to have t(3;5)(q21;q34). In about 60% of cells, the translocation was
      unbalanced, resulting in loss of the der(3) chromosome, implying that the
      critical leukemogenic sequence might reside on the der(5) chromosome. Molecular
      analysis of this case, however, failed to show rearrangement of the NPM gene and
      an MLF1/NPM transcript. A review of other reported cases of AML M6 with t(3;5)
      showed that the commonest breakpoint on chromosome 3 was also assigned to 3q21,
      as in our case. The considerable clinical, pathologic, cytogenetic and molecular
      differences observed in AML with t(3;5) suggest that these cases might be
      heterogeneous.

PMID- 9595040
TI  - Detection of chromosome over- and underrepresentations in hyperdiploid acute
      lymphoblastic leukemia by comparative genomic hybridization.
AB  - Chromosomal analysis of acute lymphoblastic leukemia (ALL) is often difficult
      because of the suboptimal in vitro growth of the immature lymphoid cell and the
      poor morphology obtained. In this study, we describe the application of
      comparative genomic hybridization (CGH) to investigate the genomic abnormalities
      in 14 patients with ALL, all of whom had cytogenetically identified numerical
      aberrations or gross chromosomal structural alteration. With the use of CGH,
      regional or whole chromosome overrepresentation or both were found to be more
      frequent than underrepresentation (52 gains vs. 6 losses), the most common gains
      being chromosomes 21 and X. The results of the comparison between CGH and
      conventional R-banding analysis could be classified into three categories: (1) in
      three cases, including two with trisomy, CGH and banding analysis gave identical
      results; (2) in six cases with hyperdiploidy and two cases presenting chromosome
      structural abnormalities, the results were consistent but with minor
      discrepancies; (3) in three cases, including two with triploidy and tetraploidy
      and one with chimeric karyotype together with +22, the data from CGH and
      cytogenetical analysis were discrepant. CGH could not find the triploidy and
      tetraploidy. Our results suggest that CGH has certain value in the detection of
      gains or losses of chromosome materials in hyperdiploid ALL. Nevertheless, the
      combination of CGH and conventional karyotyping provides more precise information
      on the genomic imbalance in ALL.

PMID- 9595041
TI  - Nonrandom pattern of telomeric associations in atypical lipomatous tumors with
      ring and giant marker chromosomes.
AB  - Atypical lipomatous tumors (ALTs) are cytogenetically characterized by
      supernumerary ring and giant marker chromosomes. Another common finding in ALT is
      that the tumor cells are cytogenetically heterogeneous with a variety of mostly
      nonclonal numerical and structural chromosome aberrations, including telomeric
      associations. In a series of 48 cytogenetically investigated ALTs, all
      chromosomal aberrations, clonal as well as nonclonal, were registered. Clonal
      ring chromosomes were present in 47 cases and giant markers in 11 cases. In 7
      cases, 12 clonal telomeric associations were found and 37 cases showed nonclonal
      associations involving 344 identified telomeres. The telomere associations were
      nonrandomly distributed, with the telomeres of 11p, 20p, 20q, 9q, 15p, 19q, and
      22q being most frequently (8.7-4.1% of all associations) involved; only Xp and Xq
      were never affected. The pattern of telomeric associations in ALT was compared
      with literature data on 47 giant cell tumors (880 telomeres), previously reported
      to show a nonrandom distribution of associations, and 36 sporadic cases of a
      variety of other human neoplasms (583 telomeres). The analysis indicated that the
      telomeres of 11p, 19q, and 20q are preferentially involved in associations in
      several tumor types. Among other structural aberrations in the ALT series, 221
      nonclonal and 52 clonal breakpoints were identified, as well as 342 nonclonal and
      14 clonal numerical aberrations. The combined data suggest that telomeric
      associations may predispose to acquired chromosome aberrations in neoplasia.

PMID- 9595042
TI  - Nonrandom numerical chromosome abnormalities in basal cell carcinomas.
AB  - Clonal chromosome abnormalities were found in 22 of 23 short-term cultured basal
      cell carcinomas (BCC) of the skin. The karyotypic abnormalities were nonrandom
      and in several cases included evidence of clonal evolution. Especially in
      cultures showing an epithelial growth pattern, simple numerical changes, most
      commonly +18, +9, +20, +7, and +5, predominated and presumably constitute
      pathogenetically important aberrations present in the neoplastic parenchyma.
      Also, several structural rearrangements of chromosome arm 9q were seen, which may
      be of particular interest against the background that a gene for familial BCC
      (Gorlin syndrome), the PTCH gene, maps to this region. Finally, most of the
      clonal aberrations detected in predominantly fibroblast-like cultures are likely
      to reflect changes acquired by cells of the tumor stroma, which raises the
      question whether mutations also of this tumor component may play a pathogenetic
      role in BCC development.

PMID- 9595043
TI  - Cytogenetic abnormalities in three patients with B-cell prolymphocytic leukemia.
AB  - We present the cytological features, conventional cytogenetics, and in situ
      hybridization (ISH) findings of three cases of B-cell prolymphocytic leukemia (B
      PLL). The diagnosis was made according to the French-American-British (FAB)
      criteria. We considered a diagnosis of B-PLL when a predominance (> 50%) of
      lymphoid cells with coarse chromatin but prominent central nucleoli and more
      abundant cytoplasm than typical chronic lymphocytic leukemia (CLL) cells were
      present. B-PLL express strong SIg, B-cell antigens, and reactivity with the
      monoclonal antibody FMC7. Chromosome analysis was carried out on lymphoid cells
      from peripheral blood and, in one patient, from lymph node. The
      phytohemagglutinin (PHA) mitogen was used. ISH was performed with two types of
      probes: the biotin-labeled chromosome 12-specific alpha satellite DNA probe to
      detect trisomy 12, and biotin-labeled libraries of whole chromosomes 1, 7, and
      14. Clonal chromosome abnormalities were found in all three patients; in one, a
      complex karyotype was observed. The most frequent recurrent abnormality was
      trisomy 12. Our results suggest that PLL usually presents with cytogenetic
      abnormalities. The finding of translocation (11;14) is noteworthy; chromosomes 1
      and 3 are also involved.

PMID- 9595044
TI  - Establishment and characterization of a human glioblastoma multiforme cell line.
AB  - Cell lines provide a useful system for further understanding the biology of
      glioblastoma multiforme. In this study, a new glioblastoma multiforme cell line,
      GATAGM-96 (Gulhane Askeri Tip Akademisi-Gliblastoma Multiforme-96), was
      established from a tumor specimen removed from an 80-year-old male patient who
      underwent surgery for intracranial tumor. Morphologic examination,
      immunocytochemical staining, growth kinetics, and karyotypic characteristics of
      this cell line were studied. The cytoskeleton was positive for neuron-specific
      enolase, vimentin, and neurofilament, and it was negative for glial fibrillary
      acidic protein, S-100 protein, p53 protein, epidermal growth factor, and
      transforming growth factor alpha. Growth kinetic studies demonstrated an
      approximate population doubling time of 38 to 42 h and a colony forming
      efficiency of 83.3%. The karyotype of the cells demonstrated it as hyperdiploid,
      with a large subpopulation of polyploid cells. There were numerous structural and
      numerical chromosome aberrations; most of them were present as clonal events. The
      phenotypic and chromosomal features detailed on the GATAGM-96 cell line should
      make it a useful addition to the cell lines currently available for in vitro and
      in vivo studies of glioblastoma multiforme.

PMID- 9595045
TI  - Chromosomal abnormalities of a new nasopharyngeal carcinoma cell line (NPC-BM1)
      derived from a bone marrow metastatic lesion.
AB  - An epithelial cell line, NPC-BM1, was established from a bone marrow biopsy of a
      female Taiwanese patient with nasopharyngeal carcinoma (NPC). Histopathology of
      the bone marrow biopsy and xenografts grown in severe combined immunodeficiency
      mice showed that the tumor was a nonkeratinizing, poorly differentiated
      carcinoma. NPC-BM1 cells grown as monolayers had a doubling time of 28.5 hours.
      Chromosome analysis showed that NPC-BM1 had the following features: 1)
      hypotetraploidy with a modal chromosome number of 87 (84-90); 2) numerically and
      structurally normal chromosomes 18; 3) numerical abnormalities without apparent
      structural alterations on chromosomes 14, 16, 17, 19, and 20; 4) ten structural
      abnormalities, t(1;9)(p11;q11), t(3;?;4)(p13;?;q13), add(4p),del(6p), i(8)
      [corrected] (q10),der(?)t(?;12),(?;p12),[corrected] add(21)(p11), del(X)(q24),
      add(X)(q22), and marker 1 (M1), in all metaphases examined, which were found to
      be present in two to five cell lines from primary NPC tumors reported previously;
      and 5) four other abnormalities,
      t(2;?;2)(p11.2;?;q21),t(11;22)(q11;q11),i(22)(q10), and marker 2 (M2), unique to
      this metastatic cell line. To the best of our knowledge, NPC-BM1 is the first NPC
      cell line derived from a distant metastatic site. Further evaluation of this cell
      line and additional metastatic NPC cell lines as well as primary NPC cell lines
      with respect to relations between the timing, karyotypic anomalies, and
      immunobiological characteristics in NPC progression and metastasis is warranted.

PMID- 9595046
TI  - Translocation (12;14) in lipoma: a case report and review of the literature.
AB  - We report a case of an intramuscular lipoma with the following karyotype:
      46,XY,t(12;14) (q14-15;q24). To our knowledge, this is the third report of a
      t(12;14) as a sole abnormality in a lipoma.

PMID- 9595047
TI  - A simple efficient method of sequential G-banding and fluorescence in situ
      hybridization.
AB  - Several methods of chromosome identification to be used in combination with G
      banding by the trypsin technique with Giemsa staining (G-banding) and
      fluorescence in situ hybridization (FISH) have been developed in the past few
      years. Unfortunately, these methods are impractical to use in the clinical
      laboratory and can provide inconsistent results. We report a simple, efficient,
      and reliable method of G-banding and FISH for use in clinical cytogenetics. G
      banded chromosomes are codenatured with a direct- or indirect-labeled DNA prove
      (by using either chromosome painting or a chromosome centromeric probe) followed
      by a hybridization and signal detection. The procedure requires no pretreatment
      or additional fixation and results in good preservation of chromosome morphology
      and good intensity of the FISH signal.

PMID- 9595048
TI  - A case of t(8;14) with total and partial trisomy 3 in Waldenstrom
      macroglobulinemia.
AB  - A case of Waldenstrom macroglobulinemia with Burkitt-type t(8;14)(q24.1;q32) and
      total and partial trisomy 3 is reported. This is an unusual combination of
      chromosomal abnormalities in Waldenstrom macroglobulinemia.

PMID- 9595049
TI  - Congenital mesoblastic nephroma and trisomy 11.
AB  - Cytogenetic analysis of a congenital mesoblastic nephroma (CMN) in a 1-month-old
      boy showed a 48,XY, +10, +11 karyotype. In this particular tumor type,
      chromosomal changes are found in almost all cases. Among the numerical changes,
      trisomy 11 stands out, whereas involvement of the long arm of chromosome 15 may
      be a nonrandomly occurring structural change.

PMID- 9595050
TI  - Acute myeloid leukemia with a novel (7;11)(q36;q13) translocation.
AB  - A 79-year-old female presented with acute myeloblastic leukemia without
      maturation. Cytogenetic studies showed a previously undescribed abnormality of
      t(7;11)(q36;q13). The significance of the involvement of 11q13 in the
      pathogenesis of myeloid leukemia is discussed.

PMID- 9595051
TI  - Translocation (3;3)(p14;q29) as the primary chromosome abnormality in a
      peritoneal mesothelioma.
AB  - Mesothelioma is a relatively rare malignant neoplasm arising from the serosal
      lining of the pleural, peritoneal, and pericardial cavities. Mesotheliomas are
      known to be associated with asbestos exposure. The karyotypes of these tumors
      have mostly been so complex as to preclude the identification of primary
      chromosome abnormalities. We present the cytogenetic analysis of two
      macroscopically distinct abdominal tumors, both diagnosed as peritoneal
      mesothelioma, occurring in a woman with a history of heavy asbestos exposure.
      Both tumors contained the same three karyotypically abnormal but cytogenetically
      related clones, with a balanced t(3;3)(p14;q29) as the primary chromosomal
      change. The fact that several chromosome abnormalities were common to both tumors
      strongly indicates that they arose through intraperitoneal spreading of a single
      neoplastic process; that is, they were not pathogenetically independent lesions.
      Our findings, taken together with previously published cytogenetic data on
      peritoneal mesotheliomas, indicate that a proportion of these tumors may be
      characterized by simple, balanced chromosomal rearrangements. At least a subset
      of peritoneal mesotheliomas arises through the same pathogenetic mechanisms that
      are involved in the pleural forms of this disease.

PMID- 9595052
TI  - Two new cases of myelodysplastic syndrome with 45,X,-X.

PMID- 9595053
TI  - A der(22)t(9;22)(p13;q11) in bone marrow cells of a patient with multiple
      myeloma: a variant of the t(9;14)(p13;q32) associated with a subset of
      lymphoplasmacytoid lymphoma.

PMID- 9595055
TI  - A thymic squamous cell carcinoma with complex chromosome abnormalities.

PMID- 9595054
TI  - Further evidence for an extra Y chromosome to represent a new primary chromosome
      abnormality in immature T-cell acute lymphoblastic leukemia.

PMID- 9595056
TI  - Origin of the mar3 in the myeloid cell line HL-60 determined by fluorescence in
      situ hybridization.

PMID- 9595057
TI  - Twenty-two years of experience in transplantation.

PMID- 9595058
TI  - Common pathways in allograft arteriosclerosis and experimental vascular injury:
      new potential sites of inhibition.

PMID- 9595059
TI  - Living-related donor liver transplantation: status quo in Kyoto, Japan.

PMID- 9595060
TI  - Antifibrinolytics and orthotopic liver transplantation.

PMID- 9595061
TI  - Immunosuppression in the 21st century.

PMID- 9595062
TI  - Liver transplantation for hepatitis C virus end-stage liver cirrhosis as compared
      with other nonviral indications.

PMID- 9595063
TI  - Early-level hepatitis C viremia after orthotopic liver transplantation is of
      prognostic significance.

PMID- 9595064
TI  - Liver transplantation across the ABO barrier: the role of plasmapheresis.

PMID- 9595065
TI  - HLA compatibility and kidney grafts from unrelated live donors. Collaborative
      Transplant Study.

PMID- 9595067
TI  - Long-term follow-up of living-related partial liver donors.

PMID- 9595066
TI  - Living-related partial liver transplantation in pediatric patients.

PMID- 9595068
TI  - Commerce in renal transplantation.

PMID- 9595070
TI  - One hundred kidney transplants: one surgeon's experience.

PMID- 9595069
TI  - Factors influencing graft survival in living-related donor kidney transplantation
      at a single center.

PMID- 9595071
TI  - Evaluation of surgical technique complications and their impact on the outcome in
      230 kidney recipients.

PMID- 9595072
TI  - Long-term follow-up of 102 living kidney donors.

PMID- 9595073
TI  - Evaluation of HLA-class I alloantibodies using PRA-STAT and complement-dependent
      cytotoxicity techniques.

PMID- 9595074
TI  - Immunophenotyping and cellular immune responses of cadaveric donor bone marrow
      cells.

PMID- 9595075
TI  - Effect of HLA-DR and class I cross-reactive group matching on first cardiac
      transplants: an analysis of access and outcome.

PMID- 9595076
TI  - Evaluation of acute kidney rejection in 230 renal transplant recipients.

PMID- 9595077
TI  - Hyperacute allograft rejection mediated by IgM antibodies and a negative
      lymphocyte crossmatch: report of two cases.

PMID- 9595078
TI  - Impact of extreme donor age on the outcome of living-related donor kidney
      transplantation.

PMID- 9595079
TI  - Outcome of pediatric renal transplantation and utilization of cadaveric donors
      under age five.

PMID- 9595080
TI  - Graft survival rates in kidney transplant recipients of different blood groups.

PMID- 9595081
TI  - Outcome of renal transplantation from elderly donors.

PMID- 9595082
TI  - Evaluation of erectile function in renal transplant recipients.

PMID- 9595085
TI  - Models for transplant coordination.

PMID- 9595084
TI  - Colonoscopy findings in renal transplant patients with abdominal symptoms.

PMID- 9595083
TI  - Assessment of total intravenous anesthesia in renal transplantation.

PMID- 9595086
TI  - The renal transplantation program at our center.

PMID- 9595087
TI  - Long-term renal retransplantation and graft survival rates at our center.

PMID- 9595088
TI  - Fifteen years of experience in vascular access surgery.

PMID- 9595089
TI  - Effect of donor feeding and fructose reperfusion on warm ischemic injury of rat
      livers.

PMID- 9595090
TI  - Religious sanctions regarding cadaveric organ transplantation in Iran.

PMID- 9595091
TI  - Brain dead donors for organ transplantation.

PMID- 9595092
TI  - Twenty-two cases of simultaneous heart, liver, and kidney transplantation from
      brain dead patients.

PMID- 9595093
TI  - Incidence of posttransplant hypertension among renal allograft recipients.

PMID- 9595094
TI  - Comparison of two biopsy techniques for renal transplant assessment.

PMID- 9595095
TI  - A comparison between alpha-fetoprotein and p53 antibodies in the diagnosis of
      hepatocellular carcinoma.

PMID- 9595096
TI  - Coronary bypass surgery in renal transplantation patients.

PMID- 9595097
TI  - Open heart surgery in patients with chronic renal failure.

PMID- 9595098
TI  - Sensitivity of radionuclide imaging, Doppler, and gray-scale ultrasound to detect
      acute rejection episodes, based on the pathologic grade of acute rejection.

PMID- 9595099
TI  - Dramatic regression of hypertensive retinopathy following renal transplantation:
      a case report.

PMID- 9595100
TI  - Anesthetic management of coronary artery bypass operation in renal transplant
      recipients.

PMID- 9595101
TI  - Outcome of living-related donor renal allografts in hepatitis C antibody-positive
      recipients.

PMID- 9595102
TI  - Quantification of hepatic microcirculation and intrahepatic shunt perfusion
      during experimental liver transplantation.

PMID- 9595103
TI  - Accelerated schedule of hepatitis B vaccination in liver transplant candidates.
AB  - Liver transplantation has become the treatment of choice worldwide for many
      patients with end-stage liver disease. In terms of survival and quality of life,
      the results of the procedure in many centers are very good. However, the long
      term function of the grafts may be affected by vascular, immunologic, or
      infection problems, the latter being a major cause of morbidity and mortality
      after orthotopic liver transplantation (OLT). Therefore, prophylactic vaccination
      against hepatitis B virus (HBV) infection is recommended in patients awaiting
      liver transplantation. Individuals with chronic advanced liver disease are known
      to be less responsive to HBV vaccination. On the other hand, the widely
      recommended standard schedule (months 0, 1, and 6) for immunization against
      hepatitis B takes 6 months, a regimen which may not be completed in time prior to
      OLT or which may not be completed due to noncompliance, possible reasons for the
      lower rates of seroprotection in OLT candidates. Studies show that, in principle,
      complete immunization with an accelerated hepatitis B vaccination protocol (0, 7,
      21 days) induces early seroprotection with excellent seroprotection rates and
      anti-HBs titers in immunocompetent individuals. We therefore performed a
      prospective clinical trial to assess immunogenicity and reactogenicity of this
      accelerated vaccination regimen in OLT candidates compared to healthy controls.

PMID- 9595104
TI  - Femoral head necrosis after kidney transplantation.

PMID- 9595105
TI  - Renal transplantation and skin diseases.

PMID- 9595106
TI  - Heparin and protamine requirements of patients in chronic renal failure.

PMID- 9595107
TI  - A simple technical modification for abdominal cardiac transplantation in rats.

PMID- 9595108
TI  - Effects of various routes of donor-specific antigen administration on graft
      survival in a model of discordant heart xenotransplantation.

PMID- 9595109
TI  - Correlation between graft mass and graft survival time in a discordant cardiac
      xenotransplantation model: a preliminary report.

PMID- 9595110
TI  - Changes in bone mineral density after renal transplantation.

PMID- 9595111
TI  - Percutaneous balloon angioplasty for permanent hemodialysis with direct
      arteriovenous fistulae.

PMID- 9595112
TI  - Liver regeneration following skin transplantation in the rat: a morphometric and
      immunohistochemical study.

PMID- 9595113
TI  - Postrenal transplant malignancies in a living-related donor program.

PMID- 9595114
TI  - Effects of alpha-tocopherol on reperfusion injury in the canine small bowel
      autotransplantation model.

PMID- 9595115
TI  - Factors relating to posttransplant erythrocytosis in renal allograft recipients.

PMID- 9595116
TI  - Conversion of patients to cyclosporine E microemulsion.

PMID- 9595117
TI  - Effects of renal transplantation on body composition.

PMID- 9595118
TI  - Monitoring of gastric PCO2 for evaluation of splanchnic mucosal microcirculatory
      impairment during mesenteric venous occlusion and reperfusion.

PMID- 9595119
TI  - Biliary endothelin levels in liver transplant recipients do not correlate with
      total bile acid concentration.

PMID- 9595120
TI  - Effect of combination of cyclosporine A and bromocriptine on survival of renal
      allografts in dogs.

PMID- 9595121
TI  - A case of Fabry's disease with normal kidney function at 10 years after
      successful renal transplantation.

PMID- 9595122
TI  - Comparison of panel reactive antibody levels with clinical and laboratory
      parameters in end-stage renal disease patients.

PMID- 9595123
TI  - Tuberculosis remains an important factor in the morbidity and mortality of
      hemodialysis patients.

PMID- 9595124
TI  - Prevalence of serological markers of autoimmunity in hemodialysis patients with
      hepatitis C virus.

PMID- 9595125
TI  - Zinc deficiency: prevalence and causes in hemodialysis patients and effect on
      cellular immune response.

PMID- 9595126
TI  - Immune mechanisms of acute rejection.
AB  - An understanding of acute allograft rejection has eluded investigators for many
      years, despite major research efforts in this area. This understanding may not be
      achievable, given the current philosophic approach to the study of immune
      processes. An alternative approach, which is outlined here, would require
      investigators to develop an appreciation for the strengths and limitations of
      complex, adaptive networks like the interdigitated inflammatory, immune, and
      physiologic processes that are at work in transplanted allografts. This
      alternative approach is offered in the hope that it will provide new insights
      regarding the nature of immune responses and will be helpful in the design and
      interpretation of future studies of acute rejection and other transplant-related
      biologic processes.

PMID- 9595127
TI  - Influence of cytokine genotypes on allograft rejection.

PMID- 9595128
TI  - Immunosuppressive effects of ursodeoxycholic acid in heart-allografted rats.

PMID- 9595129
TI  - Current experience with somatostatin analogues, especially angiopeptine, for the
      prevention of transplant vasculopathy in heart transplantation.

PMID- 9595130
TI  - Induction therapy with an immunomodulatory CD2 antibody does not inhibit
      allograft vasculopathy after rat heart transplantation.

PMID- 9595131
TI  - Impact of immunosuppression on coronary endothelial function after cardiac
      transplantation.

PMID- 9595132
TI  - Cytoimmunology in monitoring: the Munich experience.

PMID- 9595133
TI  - Tumor necrosis factor-alpha is persistently expressed in cardiac allografts in
      the absence of histological or clinical evidence of rejection.

PMID- 9595134
TI  - Immunosuppressive approaches to the prevention of graft vascular disease.

PMID- 9595135
TI  - Can molecular techniques be applied to improve the endomyocardial biopsy
      diagnosis of acute rejection?

PMID- 9595137
TI  - Role of intravascular ultrasound versus angiography for diagnosis of graft
      vascular disease.

PMID- 9595136
TI  - Malononitrilamides: a new strategy of immunosuppression for allo- and
      xenotransplantation.

PMID- 9595138
TI  - Diagnosis of acute rejection with cardiac ultrasound.

PMID- 9595139
TI  - Introducing a new clinical method for noninvasive rejection monitoring after
      heart transplantation to clinical practice: analysis of paced intramyocardial
      electrograms.

PMID- 9595140
TI  - Can ECG spectral analysis improve the noninvasive surveillance of acute
      rejection?

PMID- 9595141
TI  - Role of dobutamine stress echocardiography for diagnosis of cardiac allograft
      vasculopathy.

PMID- 9595142
TI  - The Quilty Effect: current knowledge and clinical implications.

PMID- 9595143
TI  - Chronic decrease of average peak flow velocity in coronary arteries of transplant
      recipients.

PMID- 9595144
TI  - Intracardiac dendritic cells and expression of co-stimulatory molecules after
      heart transplantation.

PMID- 9595145
TI  - CMV infection and allograft rejection.

PMID- 9595147
TI  - The genetics of atopy.
AB  - Since the original introduction by Coca and Coombs in 1923, the concept of atopy
      has always been linked to the relevance of an inherited predisposition in causing
      immediate-type hypersensitivity reactions to common allergens. However, the
      mechanisms underlying this predisposition have long been vague and controversial.
      Only recently, the better knowledge of the basic pathophysiological abnormalities
      of atopy as well as the availability of molecular biology techniques for gene
      mapping, have renewed the interest of several research groups for the genetics of
      atopy and have produced substantial progress in its understanding.

PMID- 9595146
TI  - Epstein-Barr virus mediated graft rejection in heart transplant patients:
      implication of the cardiac cytoskeleton.

PMID- 9595148
TI  - Pathomorphology of the airways in asthma.
AB  - Asthma is a chronic inflammatory disorder of the airways with a characteristic
      infiltrate of eosinophils, lymphocytes, mast cells, and monocytes in the
      bronchial epithelium and peribronchial tissue. Bronchial-, bronchoalveolar lavage
      and bronchoscopic biopsies have proved to be safe and useful techniques for
      studying the inflammatory processes in the airways, they have contributed to our
      basic knowledge concerning the pathomechanism of asthma. The data derived from
      the clinical and experimental studies have made possible to perform an
      international consensus on the diagnosis and treatment of asthma.

PMID- 9595149
TI  - T cells and eosinophils in asthma.
AB  - The bronchial inflammation characterising asthma represents a specialised form of
      cell-mediated immune reactions, in which products of activated CD4+ T cells
      orchestrate the accumulation and activation of granulocytes, particularly
      eosinophils. Through their toxic granule proteins, membrane derived lipid
      mediators and proinflammatory cytokines, eosinophils are suggested to be
      responsible for the changes in airway submucosal tissue resulting in altered
      airway responsiveness. T cell activation is followed by the synthesis and release
      of cytokines of which IL-3, IL-5 and GM-CSF are particularly important in the
      site-specific accumulation, prolonged survival and activation of eosinophils.
      This review focuses on the interaction of these two cell types with particular
      interest in the cytokines which may be responsible for the development of
      eosinophilic airway inflammation.

PMID- 9595150
TI  - Neuro-immuno regulatory mechanisms of asthma.

PMID- 9595151
TI  - Viral infections and asthma.

PMID- 9595152
TI  - Characterization of aeroallergens.

PMID- 9595153
TI  - Environmental pollution and asthma.

PMID- 9595154
TI  - Risk factors of death from asthma.

PMID- 9595155
TI  - The use of bacterial antigens in bronchial asthma.

PMID- 9595156
TI  - Sinusitis and asthma.

PMID- 9595157
TI  - The significance of lung function tests in the differential diagnosis of
      bronchial asthma.
AB  - Measurement of airflow limitation and assessment of its reversibility are
      essential in estimating the correct diagnosis of asthma. The presence of at least
      15% reversibility in FEV1 or PEF after inhalation of a short-acting beta 2
      agonist favours the diagnosis, but lack of a short-term reversibility does not
      exclude asthma. Advanced emphysema, upper airway stenosis and respiratory muscle
      weakness can, usually, be differentiated from asthma solely by their lung
      function characteristics. Monitoring of parameters (e.g. PEF) reflecting daily
      variation of airways' calibre, measurement of bronchial responsiveness to
      exercise, and to certain bronchospasmogenic mediators, non-isosmolar solutions
      may help in the differential diagnosis of asthma in a symptom-free condition.
      Cutoff values, sensitivity and specificity for asthma of these tests are
      discussed.

PMID- 9595158
TI  - The value of in vitro tests in the diagnosis of bronchial asthma.

PMID- 9595159
TI  - Occupational asthma.

PMID- 9595160
TI  - Nutritional triggers in asthma.
AB  - Food and food additive triggers play an important role in approximately 5-8% of
      all asthma cases. Exact epidemiological data are lacking, partly because the
      etiological link is not always obvious, the diagnosis of food hypersensitivity is
      often complicated and ambiguous, food triggers usually act in concert with other
      trigger(s), and intraspecies and intrabotanic cross-reactivities between inhalant
      and nutritional allergens can make the time-course of the symptoms confusing. The
      participation of airway symptoms in food allergy goes up to 40%. Relevant
      diagnosis can only be established by the combination of procedures used for both
      food allergy and asthma. In the therapy avoidance measures are of great
      importance besides usual asthma therapy, and probably in combination with the
      reduction of gut permeability.

PMID- 9595161
TI  - Inhalation devices in childhood asthma.
AB  - Inhalation therapy is currently the most appropriate way to treat asthma also in
      childhood. This route of administration provides the best clinical effect with
      the least systemic side effects. The use of inhalative therapy in childhood
      involves special considerations. The age of the child is a major determinant of
      the method which can be used. The accuracy of dosing and the technically perfect
      use of devices are extremely important, especially when drugs with potential
      systemic side effects are administered. Successful therapy needs a good
      partnership between the patient, their parents, the family doctor and the
      pulmologist.

PMID- 9595162
TI  - Inhalation devices in adult asthma.

PMID- 9595163
TI  - Preventive therapy of asthma steroid and other antiasthmatic drugs.

PMID- 9595164
TI  - Is it possible to prevent asthma?
AB  - Atopic diseases and among them bronchial asthma seem to be the worldwide epidemic
      of the end of the 20th century and this tendency may continue even in the 3rd
      millenium. The main factors and periods which are important in the genesis of
      bronchial asthma are the following: genetic influences; intrauterine
      sensitization; factors in the perinatal life; influences in infancy;
      environmental factors in childhood; bronchial asthma and "western lifestyle";
      prevention of further developing of atopic diseases.

PMID- 9595165
TI  - Bronchodilator therapy in asthma.

PMID- 9595166
TI  - Acute severe asthma.

PMID- 9595167
TI  - Immunotherapy. Theoretical basis. Traditional and alternative methods.

PMID- 9595168
TI  - Physiotherapy of asthma.

PMID- 9595169
TI  - Psychology and resocialisation of the asthmatic patients.

PMID- 9595170
TI  - Dilemmas of caring in a corporate context: a critique of nursing case management.
AB  - Nursing case management is widely acclaimed within the nursing literature as a
      form of advanced practice, beneficial for both clients and payers. However, case
      management programs involve potential conflicts between client goals and system
      goals, especially in relation to for-profit managed care systems. Early nursing
      discourse tended to minimize those conflicts, but more recent literature has
      begun to address role conflicts and ethical challenges. Feminist and critical
      theory perspectives are used to examine nursing case management in the contexts
      of capitalism and sexism, thereby illuminating recurrent dilemmas within the
      profession. The ability of nursing case management to resolve those dilemmas is
      questioned.

PMID- 9595171
TI  - So this is what it's like: struggling to survive in pediatric intensive care.
AB  - This is the story of my daughter's first 3 months of life, a time when we both
      struggled to survive while she was all but subsumed by scientific technology.
      Part I describes some common and dangerous failures of relationship which occur
      in busy hospitals. Part II describes the feelings of hope that arose in me not
      from any improvement in my child's condition, but from the ability of a few
      people to step outside of technology and science and risk what the others could
      not--authentic and caring engagement.

PMID- 9595172
TI  - Community health promotion nursing practice.
AB  - Evolving definitions of community and health promotion require the examination of
      community nursing practice. This article critically explores how the meanings of
      community may influence community nursing practice. In nursing, the most common
      definitions of community are of community as context/resource and community as
      client. The authors postulate that these definitions of community influence the
      nature of community practice. Moreover, if nurses are to practice within the
      context of health promotion, focusing on community as a relational experience,
      new patterns of community health promotion practice will need to emerge. This
      pattern of practice must honor people's experiences of community including power
      relations present in community. A new pattern of community health promotion
      nursing practice encompasses the four components of listening and critical
      reflection; participatory dialogue and critical questioning; pattern emergence
      and recognition; and movement to action.

PMID- 9595173
TI  - Praxis as a conceptual framework for participatory research in nursing.
AB  - Nursing scholars have often called upon the concept of praxis to inspire and
      inform our work. This article derives from praxis a conceptual framework for
      participatory nursing research. A praxis model can not only guide research, but
      it can also provide congruent ways to assess the quality of the project and
      ensure that researchers are accountable to the needs of the groups they study.
      The intellectual history of the term provides grounding for activist,
      collaborative, constructive science. Along with Marx and Freire's definition-in
      use, this article presents descriptions of components that are specific to the
      tasks of participatory research. A review of epistemic considerations makes the
      argument that it is possible to justify research based on a praxis-oriented
      framework.

PMID- 9595174
TI  - Pattern recognition as a nursing intervention with Japanese women with ovarian
      cancer.
AB  - This article explores the process of pattern recognition, contained within
      Newman's theory of health as expanding consciousness, as a nursing intervention
      with adults with ovarian cancer. The process of the nurse-client interactive
      pattern revealed four nonlinear phases: the client-nurse mutual concern, pattern
      recognition, vision and action potential, and transformation. Most participants
      found meaning in their lives and experienced personal growth in expanding
      consciousness.

PMID- 9595175
TI  - Ethics, economics, and the erosion of physician authority: a leadership role for
      nurses.
AB  - The emergence of managed care raises new concerns about the ethics of health care
      financing and its impact on service delivery. The current outcry, however, fails
      to recognize that American health care financing has presented serious ethical
      dilemmas for at least 50 years. What follows is a historic overview of American
      health care financing, contrasted with current challenges. The intersection
      between ethics, economics, professionalism, and public authority is explicated,
      with a critical leader/advocate role for nurses presented.

PMID- 9595176
TI  - The language of outcomes.
AB  - Outcomes are a topic of great interest. Their potential is considerable as a
      mechanism to evaluate quality, improve effectiveness, and link practice to
      professional accountability. Greater clarity and precision in the use of outcomes
      terminology will allow this potential to be realized. This article identifies the
      current confusion in outcomes terminology, begins an outcomes lexicon, and issues
      a call to action for further clarification in the language of outcomes.

PMID- 9595177
TI  - Direction of temperature control in the thermal biofeedback treatment of vascular
      headache.
AB  - In order to test for the specific therapeutic effects of thermal biofeedback
      (TBF) for hand warming on vascular headache (HA), 70 patients with chronic
      vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling,
      TBF for stabilization of hand temperature, or biofeedback to suppress alpha in
      the EEG. Patients in each condition initially had high levels of expectation of
      therapeutic benefit and found the treatment rationales highly credible.
      Participants in each condition received 12 treatment sessions on a twice-per-week
      basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and 4
      weeks after treatment, HA Index was significantly (p = .003) reduced as was HA
      medication consumption. There were no differential reductions in HA Index or
      Medication Index among the four conditions. Global self-reports of improvement
      gathered at the end of the post-treatment monitoring period also did not differ
      among the four conditions. We were unable to demonstrate a specific effect of TBF
      for hand warming on vascular HA activity.

PMID- 9595178
TI  - Facial EMG responses to combat-related visual stimuli in veterans with and
      without posttraumatic stress disorder.
AB  - Veterans with (n = 10) and without (n = 10) posttraumatic stress disorder (PTSD)
      participated in an exploratory study of facial reactivity to neutral slides and
      to slides depicting unpleasant combat-related material that were previously
      determined to be emotionally evocative. It was found that the zygomaticus major
      (cheek), masseter (jaw), and lateral frontalis (forehead) muscles were especially
      reactive to the combat slides in the veterans with PTSD, suggesting the
      importance of facial emotional expression in this disorder. The PTSD
      participants' self-reports of overall distress paralleled these effects. However,
      autonomic reactivity did not reflect general arousal effects due to the visual
      stimuli, showing both the sensitivity of facial muscle assessment in this context
      and the need for further research on the relationship between stimulus modality
      and physiological trauma reactions. Additional directions for research in this
      area are discussed including efforts to correlate subjective and physiological
      reactions.

PMID- 9595179
TI  - Stress-management training for essential hypertension: a controlled study.
AB  - Forty three patients with essential hypertension participated in a study on the
      effectiveness of stress-management training for essential hypertension. After 6-9
      clinic and 48 self-measured readings of systolic and diastolic blood pressures
      (SBP and DBP), 22 patients were treated with a program based on education,
      relaxation, and problem-solving training; and another 21 patients were assigned
      to a waiting list control group. At post-treatment, mean reductions of clinic BP
      (17/13 mm Hg vs. 6.9/4.7 mm Hg for SBP/DBP), percentages of subjects who achieved
      at least a 5 mm Hg reduction (86/86% vs. 48/48% for SBP/DBP) and percentages of
      subjects who in addition achieved a normotensive level (59/68% vs. 29/14% for
      SBP/DBP) were significantly higher in the treated group than in the control
      group. Concerning self-measured BP, the effectiveness of the stress-management
      training was not so considerable (mean reductions of 3.6/2.4 mm Hg and
      percentages of subjects who achieved a 5 mm Hg reduction of 52/38% for SBP/DBP),
      but it was significant and maintained in a 4-month follow-up assessment (mean
      reductions of 4/2 mm Hg and percentages of subjects who achieved a 5 mm Hg
      reduction of 48/33% for SBP/DBP). It is suggested that stress-management training
      can be beneficial for treatment of essential hypertension.

PMID- 9595180
TI  - Determination of the concentration of pesticides in atmosphere at high altitudes
      after aerial application.

PMID- 9595181
TI  - Statistical analysis of a steady-state method for estimating dust production and
      deposition rates in a ventilated airspace.

PMID- 9595182
TI  - Hydrocoolers: are they a mechanism for pesticide transfer?

PMID- 9595183
TI  - Organic insecticides in airborne suspended particulates.

PMID- 9595184
TI  - Implications for the use of diflubenzuron to reduce arthropod populations
      inhabiting evaporation ponds of the San Joaquin Valley, California.

PMID- 9595185
TI  - Organochlorine residues in wolves' viscera from Galicia (Northwest Spain).

PMID- 9595186
TI  - Leaching of nitrogen and phosphorus from potting media containing biosolids
      compost as affected by organic and clay amendments.

PMID- 9595187
TI  - Persistence of quinalphos and occurrence of its primary metabolite in soils.

PMID- 9595188
TI  - Levels of organochlorine pesticides residues in milk of urban mothers in Kenya.

PMID- 9595189
TI  - Heavy metal binding and removal by phormidium.

PMID- 9595190
TI  - Uptake and persistence of sodium monofluoroacetate (1080) in plants.

PMID- 9595191
TI  - Effect of selenium supplementation on the uptake and translocation of chromium by
      spinach (Spinacea oleracea).

PMID- 9595193
TI  - Aroclor 1254 does not affect the IVF of cumulus-free mouse oocytes.

PMID- 9595192
TI  - Effect of subacute exposure to lead on responses to estrogen in the immature rat
      uterus.

PMID- 9595194
TI  - Aroclor-1254 effects on the in vitro development of 8-cell mouse embryos.

PMID- 9595195
TI  - Demethylation of Acridine Orange by Arthrobacter globiformis.

PMID- 9595196
TI  - Oxidative biodegradation of an anthraquinone dye, pigment violet 12, by Coriolus
      versicolor.

PMID- 9595197
TI  - Appearance of new glycoproteins in methoxychlor-exposed sea urchin gastrulae.

PMID- 9595198
TI  - Indirect effects of esfenvalerate (insecticide) on the density of periphytic
      algae in artificial ponds.

PMID- 9595199
TI  - Dieldrin in fish and shellfish from the Mersey Estuary and Liverpool Bay.

PMID- 9595200
TI  - Sublethal bioconcentration of fenitrothion in the blood and brain of the european
      eel.

PMID- 9595201
TI  - Effects of lead on the activity of delta-aminolevulinic acid dehydratase in
      Gammarus pulex.

PMID- 9595202
TI  - Metal concentrations in tissues of the freshwater fish Capoeta barroisi from the
      Seyhan River (Turkey).

PMID- 9595203
TI  - Cognitive processing in migraine.

PMID- 9595204
TI  - Cognitive processing in migraine: a failure to find facilitation in patients with
      aura.
AB  - Recent interest in cognitive processing in migraine has been based on the
      assumption that cortical hyperexcitability in migraine with aura may manifest
      itself in the form of response time advantages in migraine as compared to
      controls. The study reported here attempted to replicate and extend the findings
      of Wray and colleagues (Brain 1995;118: 25-35). Using identical cognitive tasks,
      three experiments failed to find differences between migraine with aura patients
      and controls: furthermore, an additional group of patients without aura were also
      statistically indistinguishable from controls with respect to response times.
      Error rates were consistently high across experiments, indicating that subjects
      were responding at or near chance levels. These findings cast doubt on the
      utility of straightforward cognitive psychological methods for the study of
      cortical hyperexcitability in migraine. Some theoretical difficulties concerning
      the interpretation of response times in the context of migraine pathophysiology
      are discussed.

PMID- 9595205
TI  - Myogenic cerebrovascular autoregulation in migraine measured by stress
      transcranial Doppler sonography.
AB  - BACKGROUND AND PURPOSE: Transcranial Doppler sonography (TCD) studies may help to
      elucidate the nature and role of vascular abnormalities in migraine. Our aim in
      this study was to evaluate cerebrovascular autoregulative response in migraine
      patients with and without aura to blood pressure increase using stress TCD.
      PATIENTS AND METHODS: Using transcranial Doppler ultrasound at rest and during
      ergometer stress (stress TCD), we studied the changes in mean flow velocities and
      resistance index (RI) in relation to physical stress in the middle cerebral
      artery. Fifteen migraine patients without aura, 15 migraine patients with aura,
      and 15 healthy control subjects were examined. Patients suffered from
      predominantly unilateral headache and were studied during an attack-free period.
      The Pourcelot's RI as a measure of cerebrovascular reactivity was calculated by
      dividing the difference between systolic and diastolic velocity by the systolic
      velocity. RESULTS: None of the subgroups showed any difference during ergometer
      exercise with regard to blood pressure, endtidal CO2, heart rate, or mean flow
      velocity. In all subgroups, sufficient physical stress was achieved. With respect
      to RI change, migraine patients without aura and healthy controls did not differ
      (p > 0.05). However, the RI change of migraine patients with aura was
      significantly lower than the RI change of migraine patients without aura or
      healthy subjects (p > 0.05). The discrimination analysis showed in addition that
      RI change (absolute and as a percentage) and mean flow velocity change (as a
      percentage) could be used as diagnostic variables to detect patients with aura
      symptoms. CONCLUSION: Differences exist in cerebrovascular reactivity in migraine
      patients with aura that may contribute to the neurologic disturbances in these
      patients during attack. We propose that there is disorder of myogenic
      cerebrovascular autoregulation in migraine patients with aura during headache
      free intervals.

PMID- 9595206
TI  - Gender ratio of cluster headache over the years: a possible role of changes in
      lifestyle.
AB  - Changes in the male-to-female (M/F) ratio of cluster headache (CH) over the years
      were investigated through a comparative analysis of the distribution of the
      disease by sex and decade of onset in 482 patients (374M and 108F). Variations
      over the last few decades were also investigated in the employment rate, level of
      school education, smoking habit, and coffee and alcohol intake of the population
      living in the same area as the CH patients. The M/F ratio has fallen from 6.2:1
      for patients with CH onset before 1960, to 5.6:1, 4.3:1, 3.0:1, and 2.1:1 for
      patients with CH onset in the 1960s, 1970s, 1980s, and 1990s, respectively.
      Correspondingly, in those same decades, the M/F ratio has fallen from 2.6:1 to
      2.4:1, 2.2:1, and 1.7:1, respectively, for the employment rate, and from 8.6:1 to
      7.8:1, 3.3:1, 2.5:1, and 1.9:1 for the smoking habit. Such a close correlation
      suggests that the significant changes that have occurred over the last few
      decades in the lifestyle of both sexes--and particularly that of women--may have
      played a major role in altering the gender ratio of CH.

PMID- 9595207
TI  - Craniometric measures in cluster headache patients.
AB  - Blockade of venous drainage in the cavernous sinus, which may play a pivotal role
      in the pathophysiology of cluster headache (CH), could be triggered by local
      inflammation. It could also be favored by a constitutional narrowness of the
      cavernous sinus region. Before exploring the latter with magnetic resonance
      imaging (MRI), we determined whether external morphometric skull measures are
      different among CH patients (n = 25), healthy volunteers (n = 21), and migraine
      patients (n = 20). All subjects were males of comparable age distribution. Six
      measures were taken: inion-nasion perimeter, inion-nasion distance over the
      vertex; distance between the upper ends of tragus; diameter at the level of the
      temporal fossa; diameter at mid inion-nasion perimeter at ear level; and inion
      nasion diameter. CH patients had significantly smaller values than healthy
      subjects and/or migraine patients in all but one measure (ANOVA and Duncan's post
      hoc analysis). This may suggest that they have a narrower anterior/middle cranial
      fossa, and possibly a narrower cavernous sinus loggia, which needs to be
      confirmed by a quantitative MRI study.

PMID- 9595208
TI  - Medication patterns of recurrent headache sufferers: a community study.
AB  - This community-based telephone survey determined medication patterns of 274
      frequent headache sufferers who reported 12 or more headaches a year. Headaches
      were classified using the International Headache Society's (IHS) criteria.
      Participants reported on 465 types of headaches: 129 tension headaches, 158
      migraine headaches, 8 chronic tension headaches, and 148 headaches which were
      unclassifiable using IHS criteria. Females (n = 133) reported an average of 1.9
      types of headache and males (n = 141) reported 1.5 headache types. Fifty-six
      percent of respondents used acetaminophen for tension-type and 60% used
      acetaminophen for migraine. One percent used prescription medication for tension
      headache and 12% used prescriptions for migraine. The perceived effectiveness of
      over-the-counter medication was approximately 7 on a scale of 0-10 for tension
      headaches and 6 for migraine. Both tension-headache and migraine-headache
      sufferers waited about 1 h before taking any medication. Tension-headache
      sufferers waited until the headache was above 5 on a 0 to 10 scale (4.6 for
      migraine). It is possible that more aggressive use of medication might improve
      headache management.

PMID- 9595209
TI  - The hypnic ("alarm clock") headache syndrome.
AB  - Hypnic headache syndrome is a rare, sleep-related, benign headache disorder. We
      report 19 new cases (84% females) with follow-up data. The mean age at headache
      onset was 60.5 +/- 9 years (range 40-73 years). Headache awakened the patients
      from the night's sleep at a consistent time, usually between 1.00 and 3.00 a.m.
      (63%); three patients (16%) reported that identical headaches could occur also
      during daytime naps. Headache frequency was high, occurring more than 4
      nights/week in 68% of the patients. Headache resolution occurred within 2 h in
      68% of patients. Neurologic examination, laboratory studies, and brain imaging
      were unrevealing at the time of diagnosis. Headache severity largely remains
      unchanged or attenuates over time, but frequency may vary in either direction.
      Only one patient had spontaneous relief from headache. Four patients (24%)
      achieved permanent suppression of headache with medication, and two were able to
      abort individual headache attacks. Caffeine in a tablet or beverage was helpful
      in four patients. Lithium carbonate therapy caused side effects requiring
      cessation of treatment in four patients.

PMID- 9595210
TI  - The hypnic headache syndrome: report of three new cases.
AB  - Three new cases compatible with hypnic headache syndrome (HHS) are presented. The
      patients were 70, 77, and 79 years of age (2F, 1M). They described a history of
      nocturnal headache ranging from 5 months to 7 years. One patient was afflicted
      with diffuse pain but the other two had unilateral pain. In one patient headache
      was clearly related with dreams, but in the other two this point could not be
      confirmed. Except for headache being unilateral in two cases, the remaining HHS
      criteria were present. It is noteworthy that pain responded to flunarizine in two
      patients.

PMID- 9595211
TI  - Chronic paroxysmal hemicrania-tic syndrome.
AB  - We report the coexistence of both chronic paroxysmal hemicrania (CPH) and
      trigeminal neuralgia (tic douloureux) in a female patient. The clinical features
      combined to make a configuration of CPH-tic syndrome. The two components of the
      syndrome appeared synchronously in the same orbital region--first branch of the
      trigeminal nerve--with a latency of several years after the onset of isolated tic
      attacks of the second and third trigeminal divisions. The concurrence of both
      types of pain in the same symptomatic area may have some significance for
      pathogenic, clinical, and pharmacological aspects of such a syndrome. We discuss
      all these and postulate a provisional distinction between CPH-V2,3 tic and CPH-V1
      tic.

PMID- 9595212
TI  - Post-lumbar puncture headache.

PMID- 9595213
TI  - Management strategies for a better outcome in unstable coronary artery disease.
AB  - Unstable coronary artery disease is a term encompassing both unstable angina and
      non-Q-wave (non-ST-segment elevation) myocardial infarction. Patients with these
      conditions are at risk of early progression to acute myocardial infarction and
      death. Thus, management of these conditions must aim to reduce long-term
      mortality and morbidity. Risk stratification is crucial for the identification of
      patients whose risk of early progression is high; they may require coronary
      angiography and (if suitable) either percutaneous transluminal coronary
      angioplasty or coronary artery bypass surgery. No single variable can accurately
      predict risk, but considerable data are emerging to show that biochemical markers
      of myocardial injury, such as troponin-T and troponin-I, are valuable in
      combination with electrocardiographic findings and clinical features. Routine
      early invasive procedures (coronary angiography with or without
      revascularization) have not yet been shown to have any significant advantage over
      conservative regimens for the majority of patients. Antiplatelet, anticoagulant,
      and anti-ischemic agents remain the mainstay of treatment in the acute phase. New
      agents, such as glycoprotein IIb/IIIa receptor inhibitors and low-molecular
      weight heparins, as well as antithrombins and Factor Xa inhibitors add to the
      treatments currently available. Thrombolytic agents are contraindicated in the
      absence of ST-segment elevation. After clinical stabilization, ongoing assessment
      should include exercise testing for all patients who are able; other imaging
      techniques should be used for patients unable to exercise. A profile indicating a
      high risk of future events is an indication for elective angiography and
      consideration for revascularization.

PMID- 9595214
TI  - Noninvasive coronary angiography by contrast-enhanced electron beam computed
      tomography.
AB  - Electron beam computed tomography (EBCT) is a cross-sectional imaging method with
      high temporal and spatial resolution. So far, it has mainly been applied for the
      detection of coronary artery calcifications which permit the very sensitive
      detection of coronary atherosclerosis even in the very early stages. However,
      after intravenous injection of a contrast agent, EBCT also permits the direct
      visualization of the coronary artery lumen. For these investigations, a volume
      data set is acquired that consists of 40 axial cross-sections of the heart (3 mm
      slice thickness). To evaluate the coronary arteries as to the presence of
      stenoses and occlusions, various forms of post-processing, including shaded
      surface display, maximum intensity projection, and multiplanar reconstruction,
      are applied. The sensitivities and specificities for the detection of coronary
      artery stenoses and occlusions are about 90%. Best results are obtained for
      coronary artery bypass grafts, the left main coronary artery, and the left
      anterior descending coronary artery, while reduced image quality impairs the
      results for the right coronary artery and the left circumflex coronary artery.

PMID- 9595215
TI  - Influence of smoking status on progression of endothelial dysfunction. TREND
      Investigators. Trial on Reversing Endothelial Dysfunction.
AB  - BACKGROUND: Cigarette smoking is a major risk factor for developing coronary
      artery disease and is associated with increased coronary morbidity and mortality
      in patients with established atherosclerosis. This report describes the influence
      of smoking on coronary endothelial function in normotensive patients with
      coronary artery disease, but without left ventricular dysfunction, severe
      hypercholesterolemia, or insulin-dependent diabetes mellitus. METHODS: Placebo
      treated patients (n = 54) from a larger study assessing coronary endothelial
      function were classified at baseline as smokers or nonsmokers for this subgroup
      analysis. Patients underwent coronary angiography at baseline and again after 6
      month follow-up. RESULTS: At baseline, there was a trend for a greater decrease
      in target segment diameter (n = 54) in smokers compared with nonsmokers (-17.2 +/
      5.3% vs. -8.0 +/- 2.5%, acetylcholine 10(-4) mol/l). All measured coronary
      artery segments (n = 202) showed similar responses (-7.3 +/- 2.7% vs. -3.8 +/-
      1.3%, acetylcholine 10(-4) mmol/l, for smokers vs. nonsmokers, respectively).
      After 6 months, smokers showed an even greater vasoconstrictor response to
      acetylcholine whereas nonsmokers did not (-21.7 +/- 5.3% vs. -8.3 +/- 2.5%,
      acetylcholine 10(-4) mmol/l). The vasodilatory response to nitroglycerin was
      similar in smokers and nonsmokers. CONCLUSIONS: In current smokers, a marked
      decline in endothelium-dependent vasomotor response was observed over a 6-month
      period.

PMID- 9595216
TI  - Atheromatous plaque reflects serum total cholesterol levels: a comparative
      morphologic study of endarterectomy coronary atherosclerotic plaques removed from
      patients from the southern part of India and Caucasians from Ottawa, Canada.
AB  - BACKGROUND: Natives of South India have a very high incidence of coronary artery
      disease, despite low calorie and fat intake. HYPOTHESIS: This study was
      undertaken to determine whether morphologic features of atheromatous plaque
      reflect the serum total cholesterol. METHODS: Fifty-three endarterectomy
      specimens from patients (mean age 47 +/- 9 years, mean cholesterol 203 +/- 47
      mg/dl) obtained from one cardiac surgeon working in a single institution in South
      India were evaluated. Morphologic findings were compared with 40 endoarterectomy
      specimens obtained from age-matched Caucasians from Ottawa, Canada, with a
      reported mean cholesterol of 262 +/- 47 mg/dl. Morphometric measurements of the
      vessel size, percent stenosis, and the various components of the atherosclerotic
      plaque were determined by computerized planimetry. RESULTS: The vessel size was
      smaller in the Indian than in the Canadian population (4.6 +/- 2.9 vs. 5.6 +/-
      3.0 mm2, p = 0.07), the plaque area was less (4.3 +/- 2.3 vs. 5.3 +/- 2.8 mm2, p
      = 0.055) and the calculated percent stenosis was significantly less (93 vs. 96%,
      p = 0.028). Of all the parameters evaluated, only necrotic core in the Indian
      population (7.1 +/- 10.9% vs. Canadian 16.7 +/- 19.7%, p < 0.001) and
      proteoglycan deposition (7.9 +/- 11.2% vs. Canadian 3.7 +/- 5.3%, p < 0.023) were
      significantly different. Despite the Indians having low total cholesterol, there
      was greater diffuse double and triple-vessel disease and at a younger age than in
      the Caucasians. CONCLUSIONS: From our data, it appears that the mechanism of
      development of atherosclerotic disease in the Indians may be different because
      they have smaller vessels, smaller necrotic core, and greater proteoglycan
      deposition. Other etiologies, especially those related to a high carbohydrate
      diet (which is typical for South Indians), should be considered.

PMID- 9595217
TI  - Significance of prominent atrial-wave and diastasis deflection in radionuclide
      diastolic volume curve during exercise in detection of coronary artery disease.
AB  - BACKGROUND: Exercise testing with multigated acquisition technetium radionuclide
      cineangiography (MUGA) is a useful modality that can discriminate systolic and
      diastolic performance in patients with ischemic heart disease. However, some
      patients may have abnormal left ventricular filling dynamics with normal regional
      and global systolic function. HYPOTHESIS: The purpose of the study was to assess
      exercise-induced diastolic dysfunction as expressed by a prominent atrial (A)
      wave or diastasis deflection at the left ventricular volume curve, in patients
      with different degrees of ischemic heart disease. METHODS: In all, 32 men and 7
      women aged 35-70 years (mean 54 +/- 8.6 years) underwent MUGA at rest and during
      exercise for analysis of the radionuclide volume curve. Within 6 weeks, thallium
      201 scintigraphy and coronary angiography were performed and the patients were
      categorized into three groups: (1) disease-free (n = 10), (2) single-vessel
      disease (> 50% stenosis) (n = 19), and (3) double-vessel disease or more (n =
      10). A waves or diastasis deflections were compared among the groups. RESULTS:
      Significant differences (p < 0.01) were noted in A-wave deflection relative to
      peak diastolic volume curve during exercise (Aexe/T) between Group 1 and Groups 2
      and 3. Group 1 manifested only a mild rise in A-wave deflection from rest (20.20
      +/- 8.49%) to exercise (25.85 +/- 8.49%), whereas Groups 2 and 3 exhibited a
      significant increase from 25.89 +/- 9.55% and 28.40 +/- 12.6%, respectively, to
      60.21 +/- 22.5% and 63.0 +/- 22.86%, respectively. Group 2 had a significantly (p
      < 0.05) higher maximal heart rate than Group 3. CONCLUSIONS: The addition of
      prominent A-wave or diastasis deflection to a normal systolic response during
      exercise testing with multigated radionuclide cineangiography might be a
      sensitive marker of coronary artery disease. The A wave represents diastolic
      dysfunction of the left ventricle, considered an early event in the ischemic
      cascade.

PMID- 9595218
TI  - Acute coronary syndromes in the United States and United Kingdom: a comparison of
      approaches. The Antithrombotic Therapy in Acute Coronary Syndromes Research
      Group.
AB  - BACKGROUND: Patients with coronary artery disease are managed differently in
      different countries. HYPOTHESIS: These variations in patient management may
      affect clinical outcome, a possibility that should be taken into consideration in
      multicenter studies. METHODS: In a binational, 3 months study of antithrombotic
      treatment of patients with unstable angina and non-Q-wave infarction (ATACS), we
      compared the experience in the four enrollment centers in the United States (US)
      with the three centers in the United Kingdom (UK). The 59 US patients and the 299
      UK patients were similar with regard to age, rates of prior revascularization,
      prior positive exercise tests, medication use, and aspirin use. RESULTS: US
      patients were more commonly women (45 vs. 28%), diabetic (30 vs. 4%), or
      hypertensive (52 vs. 31%), and had a prior coronary angiogram (30 vs. 18%). After
      enrollment, coronary angiography was performed more frequently in the US than in
      the UK (61 vs. 22%). Although the distribution of coronary disease was similar,
      revascularization without recurrent angina (19 vs. 4%, p < 0.001), or following
      recurrent angina (8 vs. 3%), was significantly more frequent in the US. Combined
      primary end points (recurrent angina, myocardial infarction, or death) did not
      differ between US (29%) and UK (25%) patients. CONCLUSION: Therefore,
      international studies of acute coronary disease need to account for different
      treatments in different countries. These differences, in the small ATACS study,
      did not have a major impact on the composite primary outcome variables.

PMID- 9595219
TI  - Sensitivity and long-term prognostic value of cardiac troponin-I increase shortly
      after percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: After successful coronary interventions, minor elevations of creatine
      kinase MB (CK-MB) identified a population with a worse long-term prognosis than
      that in patients without enzyme elevations. In that setting, cardiac troponin-I
      (cTn-I), a highly specific marker for myocardial injury, was considered for a
      small study; the results did not support the view that significant myocardial
      damage occurred during successful percutaneous transluminal coronary angioplasty
      (PTCA). HYPOTHESIS: The present study was designed to assess the rate of elevated
      values of cTn-I after successful PTCA and to determine its prognostic value.
      METHODS: CTn-I and CK-MB were measured in 44 patients before and daily for 3 days
      after PTCA. Two groups of patients were considered according to the presence or
      absence of elevated levels of cTn-I. The rate of free-event survival was
      estimated for the two groups using the Kaplan-Meier method and was compared with
      the log rank test. RESULTS: Globally, 36% of patients had an increase in cTn-I
      (normal values 0.35 ng/ml) and 9% had an increase in CK-MB, p = 0.002. The mean
      time to maximal enzyme level was 1.8 days for cTn-I and 2.2 days for CK-MB. Over
      a follow-up of 1375 +/- 416 days, 18% of patients experienced adverse events, and
      cTn-I did not identify a population of worse long-term prognosis. CONCLUSION:
      These results suggest that cTn-I is more sensitive than CK-MB in identifying
      minor myocardial damage after PTCA, but these elevated concentrations of cTn-I in
      the short-term aftermath of angioplasty do not seem to be a marker of worse long
      term prognosis.

PMID- 9595220
TI  - Importance of alpha 1-sympathetic activity for diurnal change in ischemic
      threshold in patients with stable angina.
AB  - BACKGROUND: Although ischemic threshold reportedly is lower in the early morning
      than in the afternoon, the mechanisms that account for the diurnal change in
      minimal coronary vascular resistance in the potentially ischemic area are
      unknown. HYPOTHESIS: We hypothesized that calcium-channel blockers and alpha 1
      blockers may affect the ischemic threshold in the early morning and afternoon in
      patients with stable angina. METHODS: Before and after the administration of the
      calcium antagonist amlodipine (5 mg) alone and combined with the alpha 1 blocker
      prazosin (1 mg), a treadmill exercise test using the Balke-Ware protocol was
      undertaken in the morning (8:00 A.M.) and repeated in the afternoon (1:00 P.M.)
      with 15 stable angina patients. The ischemic threshold was defined as a
      reciprocal of minimal coronary vascular resistance in the presence of comparable
      levels of myocardial ischemia indicated by 0.1 mV ST depression. Minimal coronary
      vascular resistance was calculated as mean blood pressure divided by coronary
      blood flow. Since the coronary blood flow is closely related to myocardial oxygen
      consumption, which can be replaced by the double product of heart rate and
      systolic blood pressure, minimal coronary vascular resistance was approximated to
      1/heart rate. RESULTS: At baseline, minimal coronary vascular resistance was
      significantly higher in the early morning than in the afternoon (8.5 +/- 0.3 x
      10(-3) min/beats vs. 7.8 +/- 0.4 x 10(-3) min/beats, p < 0.01). Although
      treatment with amlodipine alone did not abolish the circadian pattern of minimal
      coronary vascular resistance (8.0 +/- 0.6 x 10(-3) min/beats vs. 7.7 +/- 0.6 x
      10(-3) min/ beats, p < 0.05), the addition of prazosin virtually eliminated the
      diurnal difference in minimal coronary vascular resistance (7.4 +/- 0.5 x 10(-3)
      min/beats vs. 7.5 +/- 0.5 x 10(-3) min/beats, p = NS). CONCLUSIONS: These
      findings indicate that alpha 1-sympathetic activity may play a role in the
      pathogenesis of the diurnal change of ischemic threshold in patients with stable
      angina.

PMID- 9595221
TI  - Left ventricular thromboembolism.

PMID- 9595222
TI  - Pulmonary embolism and impending paradoxical embolism: a role for transesophageal
      echocardiography?
AB  - Thrombolysis is advocated as the treatment of choice for hemodynamically
      important pulmonary embolism. This paper reports the case of a patient with
      subacute massive pulmonary embolism in which thrombolysis was not considered
      appropriate because transesophageal echocardiography demonstrated a patent
      foramen ovale and impending paradoxical embolism.

PMID- 9595223
TI  - Reversal of dilated to hypertrophic cardiomyopathy after alcohol abstinence.
AB  - Left ventricular dilation and systolic dysfunction develop in 14-16% of patients
      with hypertrophic cardiomyopathy. Such findings may easily be misdiagnosed as
      dilated cardiomyopathy. It is unknown whether left ventricular dilatation and
      systolic dysfunction in patients with hypertrophic cardiomyopathy are reversible.
      A 35-year-old man had been a heavy drinker for 13 years and was abstinent for 1
      year. Five years previously he suffered cardiac arrest and, based on
      echocardiographic, radionuclide, and cardiac catheterization findings, the
      diagnosis of alcohol-induced dilated cardiomyopathy was established. At
      presentation the heart was of normal size, with concentric left ventricular
      hypertrophy and only slightly reduced systolic function. Hypertrophic
      cardiomyopathy was diagnosed since no other cause for left ventricular
      hypertrophy could be detected. In hypertrophic cardiomyopathy, alcohol may induce
      reversible systolic dysfunction and left ventricular dilatation.

PMID- 9595224
TI  - Successful conservative treatment of nontyphoid salmonella endocarditis involving
      a bioprosthetic valve.
AB  - We report a first case of Salmonella enteritidis endocarditis involving a
      bioprosthetic aortic valve. Despite additional native tricuspid valve
      involvement, the clinical course was favorable using an antibiotic regimen of
      ciprofloxacin and netilmicin. Although Salmonella prosthetic valve endocarditis
      is considered an indication for surgical replacement of the prosthesis, this case
      indicates that prolonged treatment with fluoroquinolones may be an alternative
      provided that the hemodynamic situation is stable.

PMID- 9595225
TI  - Frans C. Donders.

PMID- 9595226
TI  - Hypocalcemic heart failure: a reversible form of heart muscle disease.

PMID- 9595227
TI  - Textural modification of processing tomatoes.
AB  - Knowledge of the textural properties of processing tomatoes is crucial to ensuing
      product acceptability; measurement, control, and optimization of these properties
      through judicious selection of varieties and control of unit operations results
      in products that the consumer prefers. It is important to first define the terms
      texture, rheology, consistency, and viscosity prior to discussing principles of
      their measurement. The textural properties of processing tomatoes may be measured
      using both sensory and objective tests, and the latter may be either destructive
      or nondestructive in nature. The unique anatomy of tomato fruit (peel, pericarp,
      columella, and locules) in part dictates the method of texture measurement.
      Numerous factors, including variety, maturity, genetic modification, cultural
      particles, and environmental conditions, processing conditions, and calcium
      addition affect the textural integrity of tomatoes. Textural properties of raw
      tomatoes and most processed tomato products are reviewed in this article.

PMID- 9595228
TI  - Proceedings from an international conference on ablation therapy for Barrett's
      mucosa. Brittany, France, 31 August-2 September 1997.
AB  - The increasing incidence of adenocarcinoma of the lower esophagus and cardia
      arising in Barrett's metaplastic epithelium continues to be of great concern
      because medical and surgical efforts to reverse the process have been
      disappointing. A potential answer to the problem is removal of the metaplastic
      epithelium. Modern technology has introduced physical and chemical modalities
      which facilitate ablation of the neo-epithelium endoscopically. These techniques
      have been used in several centers, and preliminary results are encouraging. This
      report summarizes the proceedings of an international symposium on ablative
      therapy held in Brittany, France in August 1997. Twenty-eight speakers
      contributed to the talks on the pathology, pathogenesis, current therapy
      experimental studies and clinical experience of ablation of Barrett's esophagus.

PMID- 9595229
TI  - Quality of life following esophagectomy with three-field lymphadenectomy for
      carcinoma, focusing on its relationship to vocal cord palsy.
AB  - To clarify the quality of life of patients who underwent esophagectomy for
      carcinoma by right thoracotomy, laparotomy and cervical anastomosis, 116 patients
      who were cancer free at the time of mailing a questionnaire were analyzed. A
      significant decrease in vital capacity for 3 years postoperatively, as well as in
      the percentage of ideal body weight, between 3 and 5 years were observed in 57
      patients with three-field lymphadenectomy. Patients' quality of life undergoing
      three-field dissection was worse than those with less radical lymphadenectomy (59
      cases) in terms of the performance status and difficulty in talking at 60 months
      or more postoperatively. Around 20% of all patients reported severe hoarseness
      due to permanent recurrent nerve paralysis, resulting in poor quantity of food
      intake at 24 months or less postoperatively and restricted daily activity and
      difficulty in talking at 60 months or more after the operation. When a patient
      suffers from vocal cord insufficiency caused by permanent paralysis of the
      recurrent nerve, early treatment before discharge from the hospital should be
      performed to improve the quality of life of such a patient.

PMID- 9595230
TI  - CYFRA 21-1 as a tumor marker for squamous cell carcinoma of the esophagus.
AB  - This study assessed the clinical value of CYFRA 21-1 in comparison with squamous
      cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate
      antigen 19-9 (CA19-9) in patients with esophageal squamous cell carcinoma. In 112
      primary cancer patients, the diagnostic sensitivity of CYFRA 21-1 (33.9%) was
      superior to SCC-Ag (28.6%), CEA (12.5%), and CA19-9 (6.3%). Levels of CYFRA 21-1
      were closely correlated with TNM stage and wee below the cutoff value in all 21
      patients with stage I disease. All 38 patients with a CYFRA 21-1 level over the
      cutoff value among the 80 patients who underwent esophagectomy had lymph node
      metastases (pN1). A correlation was found between CYFRA 21-1 levels and clinical
      response in serial measurements of 21 patients who received chemotherapy or chemo
      radiotherapy. Our findings suggest that CYFRA 21-1 is not useful for diagnosis,
      but that it is valuable for monitoring the efficacy of therapy.

PMID- 9595231
TI  - The value of neck drain in esophageal surgery: a randomized trial.
AB  - The use of surgical drains in certain clean elective operations remains
      controversial. To evaluate the role of closed-suction drain for an esophageal
      anastomosis in the neck, we conducted a randomized, controlled study in 40
      patients with esophageal carcinoma who underwent esophagectomy with an esophageal
      anastomosis in the neck, half of whom had a neck drain inserted at the end of
      operation. The median (range) duration of drainage was 46 hours (36 to 88 hours).
      The median (range) amount of drainage was 63 ml (15 to 210 ml). There was no
      incidence of haematoma or seroma formation in both the drained and non-drained
      groups. Anastomotic leakage did not occur in any patient. The benefits of closed
      suction neck drain could not be demonstrated. Routine use of neck drain for
      esophageal anastomosis in the neck is not necessary.

PMID- 9595232
TI  - Strategies to reduce pulmonary complications after transhiatal esophagectomy.
AB  - BACKGROUND: By eliminating a thoracotomy, transhiatal esophagectomy (THE) is
      purported to reduce postoperative pulmonary complications. However, data from
      many early series do not support this contention, documenting pulmonary
      complications in up to 50% of patients and pneumonia in 5%-20%. Since 1990, we
      have implemented a management strategy designed to maximize airway protection in
      the postoperative period. The purpose of this study was to determine the current
      incidence of pulmonary complications after transhiatal esophagectomy without
      thoracotomy. PATIENTS AND METHODS: From 1990 to 1995, 101 consecutive patients
      underwent THE. Surgical indications were esophageal carcinoma (90 patients) and
      Barrett mucosa with high-grade epithelial dysplasia (11 patients). Mean age was
      60.2 +/- 1.2 years; 89 patients were male. Eighty-two patients were smokers and
      26 had chronic obstructive pulmonary disease (COPD). Sixty-five patients were
      American Society of Anesthesiologists risk score 3 or 4. Postoperatively, all
      patients were managed according to a standardized clinical pathway that included
      overnight mechanical ventilation, chest physiotherapy, video pharyngo-esophagram
      postoperative day 6 or 7, and graduated post-esophagectomy therapeutic diet after
      acceptable esophagram. RESULTS: Pulmonary complications were classified as major
      or minor depending upon whether or not a change in therapy was required. Ten
      patients (10%) had 11 major pulmonary complications. These included pneumonia
      (3), pleural effusion requiring drainage (4), exacerbation of COPD (2), and mucus
      plug requiring bronchoscopy or intubation (2). Minor pulmonary complications
      identified by chest film were atelectasis (97), pleural effusion (85), and
      pneumothorax (3). Patients with major pulmonary complications were older (69.3 +/
      9.8 vs. 59.2 +/- 12.1 years, p < .02) and more likely to have COPD (70% vs. 21%,
      p < .005) than those with only minor complications. There were 3 operative
      deaths; 2 caused by pneumonia and 1 by fungal sepsis in a patient who had
      exacerbation of COPD. Mean hospital length of stay was 13.1 +/- 1.4 days.
      CONCLUSIONS: Minor pulmonary complications identified by chest film occur in
      nearly all patients undergoing THE. Strict adherence to a management protocol
      designed to maximize airway protection in the postoperative period results in a
      10% incidence of major pulmonary complications. Older patient age and COPD are
      risk factors for major pulmonary complications after THE. Although pneumonia is
      uncommon, it remains the most frequent cause of death after THE.

PMID- 9595233
TI  - The influence of the transposed stomach through the posterior mediastinum on the
      respiratory forced expiratory volume and forced vital capacity in patients with
      resected esophageal cancer.
AB  - Although the use of the posterior mediastinum and the stomach as a reconstruction
      option after esophagectomy has large acceptance all over the world, there are
      concerns about the potential respiratory impairment it could cause. We
      prospectively studied 35 patients regarding the forced expiratory volume and
      vital capacity. The patients were studied preoperatively and between the 45th and
      60th postoperative days. The value of both parameters decreased, although they
      were still within normal clinical ranges. We concluded that this type of
      reconstruction does not harm the patients regarding the respiratory flow rates.

PMID- 9595234
TI  - Foreign body impaction in the esophagus: are there underlying motor disorders?
AB  - We observed in our practice several cases of impaction with meat boluses without
      bony edges, in patients with patent esophageal lumen. The aim of this study was
      to search for eventual underlying motor disorders which could be responsible for
      this impaction. We included 19 patients who attended the endoscopy service for
      meat bolus impaction without organic esophageal stenosis. This group was compared
      with 18 control volunteers. Both groups underwent UGI series, UGI endoscopy and
      low-compliance perfusion standard esophageal manometry. RESULTS: Compared with
      the control group, the impacted subjects presented marked reduction in amplitude
      and duration of esophageal contraction in the proximal esophagus. CONCLUSIONS:
      These motor disorders could be responsible for the foreign body impaction in the
      esophagus. However, we believe this patient group should be further studied by 24
      hour esophageal manometry to reach a more accurate diagnosis by studying each
      patient's entire circadian cycle.

PMID- 9595235
TI  - Results of surgical treatment of cervical esophageal diverticula.
AB  - On the basis of 20 years' experience, the authors present the immediate and long
      term results of operative treatment of Zenker's diverticulum. Comparison of two
      methods of surgery--diverticulopexia (in 21 patients) and excision (in 16), both
      associated with upper esophageal sphincter myotomy--shows good immediate and long
      term results (from 1 to 19 years), with disappearance of symptoms (dysphagia) in
      all patients. There was no perioperative mortality. Postoperative complications
      were most commonly of pulmonary origin and were observed in a third of patients
      in both groups. In two patients from the group treated with excision, a leak from
      the suture line occurred, which healed spontaneously. These two patients had
      transient dysphagia in the postoperative period. On the basis of this analysis,
      the authors conclude that diverticulopexia is a safer surgical procedure than
      excision, giving less complications and a very good long-term functional result.

PMID- 9595236
TI  - Esophagocardioplasty, vagotomy-antrectomy and Roux-en-Y gastrojejunostomy:
      indication in cases with severe esophageal motor disfunction.
AB  - Almost 10% of patients with Crest syndrome associated with severe
      gastroesophageal reflux and 5-10% of patients with failed cardiomyotomy for
      achalasia present with cardial or distal esophageal organic stricture. Some of
      these cases are poor risk patients for surgery and therefore the surgeon must
      offer a safe procedure with low morbimortality, keeping in mind the
      pathophysiological motor pattern of these patients. In order to treat the
      stricture to improve the esophageal transit we treated patients with
      esophagocardioplasty associated with vagotomy-antrectomy and Roux-en-Y
      gastrojejunostomy, thereby avoiding the potential acid or biliary reflux in poor
      risk patients in whom esophagectomy would be a very deleterious procedure. All
      four patients had a good postoperative evolution and late control demonstrated
      good esophagogastric transit with no postoperative esophagitis.

PMID- 9595237
TI  - Esophageal duplication cyst: case report and review of the literature.

PMID- 9595238
TI  - Delayed traumatic rupture of the thoracic aorta into the esophagus.
AB  - A case of delayed rupture of the thoracic aorta into the esophagus after blunt
      thoracic injury is reported. It involved a hemodynamically stable 18-year-old
      male patient without any clinical or radiological signs to indicate aortic
      injury. Aortoesophageal fistula presented in the fifth post traumatic day, with a
      sudden dyspnea episode, intraperitoneal hemorrhage and lower gastrointestinal
      bleeding, due to intraperitoneal and intragastric rupture of intramural
      esophageal hematoma.

PMID- 9595239
TI  - Pedunculated liposarcoma of the esophagus.
AB  - Polypoid tumors of the esophagus present diagnostic and therapeutic problems.
      Liposarcomas are infrequent among them. We report a recent case. A 73-year-old
      male patient was seen in May 1995 in the Ear, Nose and Throat (ENT) Department,
      Clinica Modelo de Moron, with intermittent dysphagia and dyspnoea due to
      recurrent vomiting. A laryngeal lineal tomography showed a subglottic obstruction
      due to extrinsic compression. The patient was referred to the Gastroenterology
      Department, where an upper gastrointestinal (upper GI) series demonstrated mega
      esophagus with abundant retained food. Endoscopy showed a large intraluminal mass
      covered by normal mucosa which arose on the posterior wall. Videofluoroscopy and
      chest CT diagnosed a probable polypoid lipoma due to its densitometric
      characteristics. The tumour was resected by left cervicotomy and left
      esophagotomy. The patient's progress to date is favourable. Pathology studies
      showed a well-differentiated liposarcoma. According to the literature, the first
      case was reported in 1983, and ours is only the seventh case in the world to be
      documented.

PMID- 9595240
TI  - Tuberculosis of the esophagus.
AB  - We report a case of a patient with esophageal tuberculosis, a very uncommon form
      of extrapulmonar tuberculosis. Initially, because of constitutional
      symptomatology and radiological findings of mediastinal lymph node enlargement,
      lymphoma was considered. However, the endoscopic findings of ulcerative masses
      and a sinus tract revealed by esophagram were suspicious of tuberculous origin.
      Diagnosis was achieved after bacterial examination of smear samples from
      esophageal ulcers that revealed bacillus tuberculous and histological
      demonstration of caseating granulomas in cervical lymph nodes. Tuberculous
      mediastinal lymphadenitis was thought to be source of the spread to esophagus.
      The patient was successfully treated with a three antituberculous drugs regimen.
      In spite of its rarity, even in patients without risk factors, the diagnosis
      would be considered in the differential diagnosis of uncertain esophageal
      lesions.

PMID- 9595241
TI  - Palliation of anastomotic tumor recurrence after esophagectomy and gastric
      transposition: cervico-mediastinal resection and reconstruction by using a free
      jejunal transplant.

PMID- 9595242
TI  - Community involvement in assessing health needs of immigrant Salvadoreans living
      in Washington, D.C. area.

PMID- 9595243
TI  - Race, education, and dietary cations: findings from the Third National Health And
      Nutrition Examination Survey.
AB  - Hypertension, which has been associated with high intake of sodium and low intake
      of calcium, magnesium, and potassium, is highly prevalent among African
      Americans. To examine differences in dietary intakes of calcium, magnesium, and
      potassium between whites and African Americans, and the effect of education on
      these differences, the author analyzed data from a nationally representative
      sample that participated in the first phase of the National Health and
      Examination Survey III from 1988-1991. The analytic sample included 6,046 white
      participants and 2,226 African-American participants with complete information
      for age, race, education, and diet. Dietary information was collected from a
      single 24-hour dietary recall. African Americans consumed less calcium,
      magnesium, and potassium than whites regardless of educational achievement.
      Sodium intakes from diet were similar between the two groups. Among whites,
      intakes of calcium, magnesium, and potassium were positively related to
      educational attainment. Among African Americans, only magnesium intake was
      positively related to educational attainment. Because the prevalence of
      hypertension among African Americans exceeds that among whites, increases in the
      consumption of calcium, magnesium, and potassium could help to prevent and
      control excess hypertension among African Americans.

PMID- 9595244
TI  - Relation of traditional risk factors to intrauterine growth retardation among
      United States-born and foreign-born Mexican Americans in Chicago.
AB  - OBJECTIVES: To determine the relation of traditional sociodemographic
      characteristics to the small-for-gestational age rates of urban Mexican
      Americans. DESIGN: A cross-sectional study. METHODS: We performed a stratified
      analysis of 1982-1983 Illinois vital records and 1980 U.S. Census income data.
      The authors analyzed the 1982-1983 Illinois vital records and 1980 U.S. Census
      income data to determine whether maternal sociodemographic characteristics are
      associated with the small-for-gestational age (weight-for-gestational-length <
      10th percentile) rates among Mexican Americans in Chicago. RESULTS: The small-for
      gestational age rate was 2.1% for infants with U.S.-born mothers (N = 2,253)
      compared to 1.4% for infants with foreign-born mothers (N = 8,746); relative risk
      1.5 (95% confidence interval 1.1-2.1). For the U.S.-born cohort, maternal
      education, marital status, parity, prenatal care, and community income were
      associated with small-for-gestational age rates. In contrast, with the exception
      of marital status, these commonly cited risk factors were not associated with the
      small-for-gestational age rates of infants with Mexican-born mothers. The U.S.
      born:Mexico-born small-for-gestational age rate ratio fluctuated around 2 among
      mothers with a high-risk (maternal age < 20 years, < 12 years education,
      unmarried marital status) demographic profile. CONCLUSIONS: We conclude that
      traditional sociodemographic risk factors have different reproductive outcome
      consequences for U.S.-born and foreign-born Mexican-American mothers.

PMID- 9595245
TI  - Community's role in the promotion of recovery from addiction and prevention of
      relapse among women: an exploratory study.
AB  - OBJECTIVE: This exploratory study examined the community's role in the promotion
      of recovery from addiction and the prevention of relapse among women, and the
      differences in women's addiction and recovery by ethnicity. Community was defined
      as six institutions: home, church, workplace, school, law enforcement and medical
      care system. METHODS: The study sample consisted of 39 Anglo and 24 ethnic
      minority women (21 African American; 3 Hispanic) between the ages of 21 and 70,
      living along the Gulf Coast of Texas, who had been in continuous recovery from
      addiction to alcohol or other drugs for at least six months. The study was cross
      sectional, and data were collected through the use of structured interviews
      utilizing the Women in Recovery Questionnaire, an instrument developed by the
      investigative team. RESULTS: This study found that community institutions
      (church, school, home, workplace and law enforcement and medical systems) were
      seldom involved in promoting recovery or preventing relapse in women, with the
      exception of the home, which supported recovery. Anglo and ethnic minority women
      differed by primary drug usage, number of times in treatment, religion,
      perception of sexism, and likelihood of citations for traffic violations.
      CONCLUSION: Large, randomized studies are needed to investigate the community's
      role in women's recovery from alcohol and other drugs.

PMID- 9595246
TI  - Mortality among blacks living in census tracts with public housing projects in
      Hartford, Connecticut.
AB  - OBJECTIVE: The study examined mortality among blacks (African Americans) living
      in census tracts with a large public housing project(s). DESIGN: Standardized
      mortality ratios (SMRs), or the ratios of observed to expected numbers of deaths,
      from all causes and from selected specific causes were analyzed. SETTING: SMRs
      were analyzed for 1988-91 for blacks in four census tracts in Hartford, CT.
      Expected numbers of deaths were based on age-specific death rates for all blacks
      in the city. RESULTS: The SMR for all causes of death combined was statistically
      significantly elevated for black male (but not black female) residents of the
      four census tracts combined, due in part to statistically significantly elevated
      SMRs for both cancer and cardiovascular diseases (and for the subcategory of
      coronary heart disease). However, differences in SMRs for black males were
      evident among the four census tracts, which did not appear to be explained by
      differences in black poverty rates among these tracts. CONCLUSION: Research is
      needed on quality of life and health care among black residents of different
      housing projects in Hartford, and in other U.S. cities.

PMID- 9595247
TI  - The impact of social class on the use of cancer screening within three
      racial/ethnic groups in the United States.
AB  - Despite the consistent and strong association of social class with health status,
      the extent to which racial/ethnic disparities in cancer screening reflect social
      class is rarely addressed. We hypothesized that the use of cancer screening is
      positively correlated with social class for black, white and Hispanic Americans.
      Data from the 1987 and 1992 National Health Interview Survey Cancer Control
      Supplements were compared for each racial/ethnic group by income, education, age,
      and gender. For each racial/ethnic group, individuals with less education or
      income are less likely to be screened. Although specific subgroups increased
      their use of screening modalities between 1987 and 1992, older black Americans
      who were poor or had less education reported less screening than similar older
      white Americans. Although social class is a powerful explanatory variable for
      younger Americans, racial disparities in cancer screening persist among older
      black Americans.

PMID- 9595248
TI  - Impact of selected medical conditions on self-reported lower-extremity function
      in Mexican-American elderly.
AB  - OBJECTIVE: To examine the independent impact of common medical conditions on
      lower-extremity function in Mexican-American elderly. DESIGN: Cross-sectional
      study using a probability sample of non-institutionalized Mexican Americans aged
      65 or older. SETTING: The five Southwestern states, Texas, New Mexico, Arizona,
      Colorado and California. PARTICIPANTS: All subjects were interviewed in person (n
      = 2,873) or by proxy (n = 177) in their homes during late 1993 and early 1994.
      MAIN OUTCOME MEASURES: Respondents were asked whether they could perform four
      activities related to lower-extremity function without help: walking across a
      small room, getting from a bed to a chair, walking up and down stairs, and
      walking half a mile. A summary measure of lower body disability created from
      these four items was regressed on seven common medical conditions plus five
      control variables using multiple logistic regression. RESULTS: Adjusted Odds
      Ratios (OR) suggested that impaired lower-extremity function was associated with
      previous diagnosis of hip fracture (OR = 4.28), stroke (OR = 3.47), lower
      extremity arthritis (OR = 2.60), heart attack (OR = 2.29), diabetes (OR = 2.03)
      and obesity (OR = 1.50). Impaired lower-extremity function was significantly
      associated with older age (75+ years old), gender (female) and marital status
      (unmarried). In addition, there was a linear increase in the risk of function
      loss by number of medical conditions. CONCLUSIONS: It appears that Mexican
      American elderly diagnosed with medical conditions, especially stroke and hip
      fracture, have a high risk for lower-extremity dysfunction. These findings have
      implications for efforts to prevent or reduce lower-extremity dysfunction, as
      well as for the provision of community-based long-term care services for Mexican
      American elderly.

PMID- 9595249
TI  - Lipoprotein(A) and coronary heart disease risk factors in a racially mixed
      population: the Johns Hopkins Sibling Study.
AB  - OBJECTIVES: To determine if heart disease risk factors differentially affect
      lipoprotein(a) concentration by race, we assessed the association of
      lipoprotein(a) with heart disease risk factors in healthy Caucasians and African
      Americans with family histories of premature heart disease. METHODS: Participants
      (403 Caucasian and 148 African American), all less than 60 years old and free of
      heart disease, were recruited through a brother or sister diagnosed with coronary
      heart disease before age 60. Risk factor information was elicited through an
      interview and medical examination. RESULTS: As expected, lipoprotein(a) was
      significantly higher among African Americans than among Caucasians. Mean
      lipoprotein(a) concentrations were positively associated with smoking status and
      age, and negatively associated with hypertension in African Americans. Smokers
      had lipoprotein(a) levels 38% higher than nonsmokers. Conversely, lipoprotein(a)
      concentrations were unrelated to heart disease risk factors among Caucasians.
      CONCLUSION: While this study confirms that lipoprotein(a) concentration is
      independent of CHD risk factors in Caucasians, lipoprotein(a) appears to be
      related to several CHD risk factors in African Americans at high risk for
      premature heart disease. Given the high levels of lipoprotein(a) in people of
      African descent and lipoprotein(a)'s link to cardiovascular diseases, more
      research is needed to understand the relationship of lipoprotein(a) to heart
      disease risk factors and the subsequent disease in African-American populations.

PMID- 9595250
TI  - Church-related correlates of tobacco use among Lumbee Indians in North Carolina.
AB  - BACKGROUND: Although minority populations suffer a disproportionately higher
      burden of tobacco-attributable morbidity and mortality, the church appears to be
      a promising avenue through which to pursue tobacco-cessation interventions in
      these communities. This report describes church-related correlates of tobacco use
      among the Lumbee Indians in North Carolina, a population with a high prevalence
      of tobacco use, strong ties to tobacco-related agriculture, and high levels of
      church participation. METHODS: A cross-sectional telephone survey of 400 adult
      Lumbee Indians was carried out in Pembroke, a town in Robeson County, NC. The
      questionnaire elicited information on tobacco use, demographic and social support
      information, knowledge and practices related to tobacco agriculture and
      traditional Native American tobacco use and church participation. RESULTS: Sixty
      three percent of participants were church members and 82% said the church is
      "very important" to the Lumbee community. In bivariate analysis, church
      attendance over the past year correlated with age, education, gender, number of
      close friends and relatives, marital status and current smoking status. Church
      attendance was not related to current smokeless tobacco use or participation in
      tobacco-related agriculture. Current smokers who had not attended church in the
      past year smoked significantly more cigarettes per day than current smokers
      attending church more often. In logistic regression, participants attending
      church weekly or more often were 73% less likely to be current smokers (adjusted
      odds ratio [AOR] = 0.27, 95% confidence interval [CI] = 0.11-0.68). Among ever
      smokers, participants having attended church infrequently in the past year were
      79% less likely to have quit (AOR = 0.21, 95% CI = 0.07-0.65). Having
      participated in tobacco agriculture as a child predicted current Christian views
      on tobacco use. DISCUSSION: Tobacco use, common among Lumbee adults, correlates
      with a variety of demographic and social support variables. In addition, these
      data are the first to uncover a dose-response relationship between church
      attendance and number of cigarettes smoked per day by current smokers, and the
      relationship between childhood participation in tobacco agriculture and Christian
      views on tobacco use. Our results should be useful in designing a church-based
      tobacco-cessation intervention among Lumbee Indians.

PMID- 9595251
TI  - Validity and reproducibility of a food frequency questionnaire among Hispanic and
      non-Hispanic white women in New Mexico.
AB  - The purpose of this study was to assess the validity and reproducibility of an
      interviewer-administered, semi-quantitative food frequency questionnaire (FFQ)
      among 132 volunteer New Mexico Hispanic (H) and non-Hispanic white (NHW) women,
      aged 35-74 years, with (n = 47) and without (n = 85) a breast cancer history, and
      to add to the limited data presently available on the performance of FFQs among
      different ethnic groups. Validity was measured at one month and six months from
      baseline against four-day food records, and reproducibility was tested by
      comparing FFQs. Unadjusted validity correlation coefficients were highest at one
      month, ranging from 0.38 (polyunsaturated and monounsaturated fat) to 0.57
      (calcium); energy-adjusted correlation coefficients were highest at six months,
      ranging from 0.15 (polyunsaturated fat) to 0.68 (calcium). Energy-adjusted
      correlation coefficients were statistically significant by ethnicity for vitamins
      A and C, protein, carotene and calcium, and by case status for saturated fat,
      folate, fiber, and vitamins A and E. Reproducibility correlation coefficients
      (unadjusted) ranged from 0.40 (polyunsaturated fat) to 0.71 (carbohydrate,
      retinol); energy-adjusted correlation coefficients ranged from 0.42 (vitamin E)
      to 0.78 (fiber), and differed significantly by ethnicity for saturated fat and
      retinol, and by case status for carbohydrate. Overall, our FFQ has comparable
      characteristics to other FFQs and is suitable for use with New Mexico's H and NHW
      women.

PMID- 9595252
TI  - Obesity in African Americans: biobehavioral consequences of culture.

PMID- 9595253
TI  - Calcium antagonists--pharmacologic considerations.
AB  - Calcium antagonists work by blocking the entrance of calcium from the outside of
      the cell to the inside of the cell through the voltage-dependent calcium
      channels. There are three major L-type (high voltage) calcium channel blocker
      sites (a dihydropyridine site for nifedipine, a phenylalkylamine for verapamil,
      and a benzothiazepine site for diltiazem) and a tetralol T-type (low voltage)
      calcium antagonist. Calcium antagonists differ in terms of their tissue affinity
      and vascular selectivity resulting in different therapeutic applications. The
      initial disadvantage of a short-half has been overcome with drug delivery systems
      that lower blood pressure over a twenty-four hour period. These calcium
      antagonists are effective in lowering blood pressure and reducing anginal
      episodes in African Americans and whites, regardless of age or renin level.

PMID- 9595254
TI  - Toward improved antihypertensive therapy with calcium channel blockers.
AB  - Outcome trials are the scientific method of determining if an antihypertensive
      agent really works; and for a therapy to work well, it should reduce mortality.
      The FDA requires only that blood pressure be controlled safely, but current
      evidence-based medicine demands answers to the mortality/morbidity question. We
      need this outcome trial information on all the classes of antihypertensives,
      including calcium channel blockers. For example, we often rely on surrogate
      endpoints such as control of blood pressure or control of PVCs. If we treat
      hypertensives with PVCs using beta-blockers or calcium channel blockers, we may
      see both control of blood pressure and suppression of PVCs. However, as we
      learned from the CAST trial with flecainide and encainide, PVCs can be
      controlled, but mortality may increase. On the other hand, the Lewis trial
      demonstrated that captopril, an ACE inhibitor, reduced proteinuria, which is
      another surrogate endpoint in diabetic hypertensives with nephropathy, although
      blood pressure was controlled with diuretic and conventional therapy.
      Importantly, captopril also reduced morbidity and mortality without influencing
      blood pressure. Unfortunately, there are no outcome trials measuring mortality
      endpoints for most of the antihypertensive agents in use today, especially in
      patients with uncomplicated hypertension.

PMID- 9595255
TI  - Physiologic rationale for calcium antagonist therapy in essential hypertension.
AB  - Two basic concepts that are relevant to hypertensive cardiovascular disease are
      often ignored despite being central to a proper understanding and clinical
      approach to our patients. First, high blood pressure is an abnormal physical
      sign; a 'vital' sign, as are temperature, pulse, and respiration. Although people
      often consider hypertension as a disease, it is itself not a disease, but rather
      one sign of a disease: a warning manifestation of a disease. Approximately 90% of
      the time, the underlying cause(s) of this sign are unknown and, thus, the
      condition itself is named according to its sign, as essential hypertension.
      Commonly, physicians are told that by eliminating the messenger bearing the bad
      news--i.e., by merely suppressing the blood pressure, the excess morbidity and
      mortality associated with the underlying disease process will be reversed.
      Unfortunately, the cumulative experience of over two decades of world-wide
      clinical trials indicates that getting rid of only one aspect of hypertensive
      disease, the elevated blood pressure, gets rid of only part of the excess
      cardiovascular risk associated with hypertension. By contrast, we now appreciate
      that what we call hypertension carries with it other peripheral manifestations
      present in other body systems, such as left ventricular hypertrophy, that may
      exist prior to and progress independently of the hypertension itself; and insulin
      resistance, reflecting the same underlying pathophysiology in skeletal muscle,
      fat, and other tissues. Thus, the disease we call hypertension is not just a
      'numbers' game. As such, a reasonable goal not yet attained would be to identify
      common factors underlying not only the elevations of blood pressure, but the
      other multisystemic aspects of hypertensive cardiovascular disease as well.
      Focusing on such underlying factors would allow treatment of the disease process
      itself, rather than just the level of blood pressure. A second concept, also
      often overlooked but quite obvious, is the pathophysiologic and clinical
      heterogeneity of hypertension. People are different. By analogy with an elevated
      temperature, the same elevation of blood pressure that leads to the diagnosis of
      'essential' hypertension may result from many different "primary" causes, which
      just happen to have hypertension as one shared clinical manifestation. This
      immediately implies that when we ask, "Is this drug good, or preferred for
      hypertension?" the answer should be, "It depends." As an obvious example, to be
      discussed in more detail below, the salt-sensitive hypertensive responds to
      dietary salt recommendations and to different drug classes differently from an
      individual who is not salt-sensitive.

PMID- 9595256
TI  - Calcium antagonists in African-American patients.
AB  - When initiating monotherapy for the treatment of essential hypertension, multiple
      determinants factor into the decision. The goal of treatment is to lower blood
      pressure and lessen the likelihood of progression to target organ failure.
      Physicians frequently prioritize these determinants and make decisions to
      initiate monotherapy based on the race of an individual. All too often, however,
      the black/white issue is overstated and given too much consideration. The overall
      goal of this review is to suggest the appropriate "role" for racial profiling in
      the initial selection of an antihypertensive agent.

PMID- 9595258
TI  - Molecular basis of the altered gag p19 protein (MA) of the transformation
      defective mutant of Rous sarcoma virus, tdPH2010.
AB  - The transformation-defective mutant of Rous sarcoma virus (RSV), tdPH2010, has a
      gag p19 (matrix; MA) protein which migrates on SDS-polyacrylamide gels faster
      than that of the parental (tsNY68) as well as other wild-type strains of RSV. To
      study the molecular basis of this altered migration pattern and its biological
      significance, the nucleotide sequence of the p19 region of tdPH2010 was
      determined. Comparison of the nucleotide sequence of tdPH2010 with that of the
      Schmidt-Ruppin A strain of RSV revealed a point mutation at nucleotide 755 (G to
      A), resulting in an amino-acid substitution at residue 126 of p19 (Glu to Lys).
      Acidic-methanol esterification of free carboxyl groups suppressed the difference
      in electrophoretic mobility of p19 between tdPH2010 and the wild-type virus.
      Recombinant virus constructs having the mutated gag region of tdPH2010 produced a
      p19 with the same electrophoretic mobility as the p19 of tdPH2010. We concluded
      that the point mutation caused the altered electrophoretic behavior of p19 of
      tdPH2010. The mutation had no effect on the growth of infected cells.

PMID- 9595257
TI  - Calcium antagonists--clinical considerations.
AB  - Calcium antagonists are useful for treating hypertension, stable exertional and
      vasospastic angina, and supraventricular arrhythmias. Recent studies have proven
      their ability to decrease the rate of nonfatal strokes. Short-acting calcium
      antagonists should be avoided with hypertensive emergencies and urgencies,
      unstable angina, and acute myocardial infarction. The use of calcium antagonists
      in systolic heart failure should not be as the primary therapy. Care must be
      taken in using non-dihydropyridines because of multiple drug-drug interactions.
      Prospective trials are in progress through the next decade that will compare
      traditional drugs such as diuretics and beta-blockers to calcium antagonists,
      converting enzyme inhibitors, and angiotensin II receptor blockers.

PMID- 9595259
TI  - Mapping of selective rat chromosome regions using mouse microsatellite markers.
AB  - Four hundred eighty mouse microsatellite markers distributed in discrete regions
      on five mouse chromosomes were screened for producing PCR products in the rat.
      Ninety-eight of these markers or 20% give distinctive PCR products. Among these
      ninety-eight markers, twenty-three are polymorphic between the inbred
      hypertensive Dahl salt-sensitive (S) rat strain and several normotensive rat
      strains of interest. Fourteen of these polymorphic markers have been mapped to
      the homologous chromosome regions of the rat, and have further been utilized to
      localize quantitative trait loci (QTL) for blood pressure in the S rat.

PMID- 9595260
TI  - The effect of an antiphlogistic incorporated in liposomes on experimentally
      induced inflammation.
AB  - The antiphlogistic Ibuprofen incorporated in liposomes caused a decrease of the
      inflammatory edema induced by Carrageenan in the distal part of the rat's hind
      leg after both the intramuscular and percutaneous administration. The
      antiphlogistic effect of free Ibuprofen in the cream was weaker. Intramuscular
      administration of empty liposomes slowed down in the initial stages the
      development of inflammation and slightly diminished the size of edema.

PMID- 9595261
TI  - DNA diagnosis and clinical manifestations of autosomal dominant polycystic kidney
      disease.
AB  - At least 2 genes, detectable by DNA methods, encode autosomal dominant polycystic
      kidney disease (ADPKD), which remains the most frequent and serious hereditary
      renal disease. PKD1 gene, localized on chromosome 16, responds for the clinical
      course in the majority of ADPKD patients, whereas PKD2 gene, localized on
      chromosome 4, is responsible for less than 10-15% of cases, with presumed milder
      phenotypic manifestations. To start the clinical and genetic correlation in
      patients with different genotypes (PKD1 vs. PKD2) in the Czech population, a
      pilot group of 88 patients with ADPKD was analysed. Families with PKD1 (n = 44)
      represented 95.6% and families with PKD2 (n = 2) 4.4% of all families
      investigated (n = 46). Our clinical analysis, yet based only on a limited number
      of PKD2 subjects, does not definitely support the concept of a milder phenotype
      and prognosis in PKD2 versus PKD1 patients, in terms of mean age of diagnosis (29
      vs. 29 years), mean age at onset of arterial hypertension (33 vs. 33 years), more
      favourable renal function or ultrasound findings.

PMID- 9595262
TI  - Identification of APC exon 15 mutations in families suspected of familial
      adenomatous polyposis (FAP).
AB  - Patients with familial adenomatous polyposis coli (FAP) reveal numerous
      colorectal adenomas as well as benign and malignant extracolonic lesions.
      Adenomatous polyposis coli (APC) gene mutations are the crucial genetic defect in
      FAP. The APC mutation molecular analysis of 20 FAP families was performed using
      the novel and effective method of the heteroduplex analysis (HDA). All of these
      families were screened for mutations in APC exon 15. APC mutations were
      identified in 4 individuals of two families. These two families were also
      screened by the protein truncation test (PTT). The PTT results confirmed previous
      findings obtained by HDA. The results of molecular analysis were correlated with
      the clinical manifestations of extracolonic lesions and congenital hypertrophy of
      retinal pigment epithelium (CHRPE). Positive correlation of all clinical
      examinations and mutations of APC gene was observed in all 4 FAP patients.

PMID- 9595263
TI  - The genetic basis of primary, predominantly specific immunodeficiencies.
AB  - The presented review lists primary immunodeficiencies which essentially involve a
      mutation in genes coding for functionally important molecules, membrane antigens
      (e.g., MHC), chains of lymphokine receptors, protein kinases of the signal
      cascade, transcription factors, and some important regulators of cellular
      metabolism. Mutations are expressed as early as during embryogenesis
      (lymphopoiesis-I) as well as during induction of the immune response by antigen
      ligand binding to cell receptors, TCR, BCR (immunopoiesis-II). Immunodeficiencies
      are classified by the stage of development (I) or immune response induction (II)
      in which they occur most markedly, even in clinical terms. It has been pointed
      out that the same autoactivation stimuli and mechanisms, allowing differentiation
      maturation of cells during embryogenesis (action of stem cell factor (SFC), IL-3,
      IL-7, and activation cascade), serve even later as a functional prerequisite for
      an adaptive immune response to antigen. As a result, this attempt to classify
      primary immunodeficiencies by differentiation periods (when they become evident
      most markedly in terms of their function) has an inherent logical limitation.
      Some early mutations turn immediately lethal, some express themselves by blocking
      embryonic lymphopoiesis while other mutations do not become demonstrable until
      after cell stimulation by antigens. This explains why the developmental
      differentiation scheme is bound to turn, in the future, into an immunodeficiency
      classification by localization of gene mutations and their incidence in time,
      e.g., increased mutation incidence during proliferation following cell
      stimulation by antigen stimuli.

PMID- 9595264
TI  - Comparative evaluation of four genotyping methods for hepatitis C virus.
AB  - Four most widely accepted genotyping methods for hepatitis C virus (HCV) were
      applied to 40 HCV RNA isolates obtained from Slovenian patients in order to
      determine the concordance and applicability of various genotyping systems. The
      four methods are: (i) amplification of the core region with genotype-specific
      primers; (ii) nested polymerase chain reaction (PCR) in the core region followed
      by hybridization to HCV type-specific probes; (iii) reverse hybridization with
      the line probe assay Inno LiPA (Innogenetics, Gent, Belgium) using type-specific
      probes for the 5' non-coding region (NCR); and (iv) restriction fragment length
      polymorphism analysis of DNA amplified from the 5' NCR. Additionally, in isolates
      with discordant results nucleotide sequence analysis of a part of the NS-5 region
      was performed. Both genotyping methods based on the analysis of the 5' NCR were
      found more sensitive than those methods based on the analysis of the HCV core
      region. None of the four genotyping methods correctly classified all Slovenian
      HCV RNA isolates. PCR with genotype-specific primers was identified as entirely
      unsuitable for genotyping of Slovenian HCV RNA isolates. The remaining genotyping
      methods could clearly differentiate between HCV genotypes, but were not entirely
      reliable for HCV subtyping. The specificity of genotyping methods, which are
      based on the 5' NCR or the core region, was occasionally hampered, due to a lack
      or excess of sequence variation in their respective target regions.

PMID- 9595265
TI  - Genotoxicity of purine acyclic nucleotide analogs.
AB  - The genotoxic and embryotoxic effects of phosphonomethoxyalkylpurines, a new
      group of antiviral agents, decrease in the following order: PMEG > PMEthioG >
      PMEDAP > PMEA > (R)-PMPDAP = (R)-PMPA. Results of the present study are fully
      consistent with the previously found efficacy of their diphosphates to inhibit
      the replicative DNA polymerases. The marked genotoxicity of PMEG and PMEthioG is
      comparable to that of mitomycin C, whereas the moderate genotoxicity of PMEA is
      comparable to that of AZT. (R)-PMPDAP and (R)-PMPA did not induce any structural
      aberrations of chromosomes under the experimental conditions.

PMID- 9595266
TI  - Modification of postradiative changes of nucleic acids by the bacterial extract
      broncho-vaxom in rat tissues.
AB  - We have studied the influence of immunomodulator Broncho-Vaxom on the
      concentration and the total content of RNA and DNA in the bone marrow, spleen and
      regenerating liver (after partial hepatectomy) in rats irradiated with doses of 3
      Gy, 6 Gy or 9 Gy of gamma radiation. Animals in all groups were partially
      hepatectomized (2/3 of liver mass removed) within 30 min or on the 6th and 13th
      day after irradiation and they were examined 30 h after resection, i.e., on the
      1st, 7th and 14th day after irradiation. Broncho-Vaxom was administered
      intraperitoneally at the dose of 1.5 mg/rat 24 h before irradiation. We have
      found that administration of Broncho-Vaxom decreased the loss of RNA and DNA
      induced by radiation in the bone marrow and partly also in the spleen of rats
      irradiated with doses 3 and 6 Gy over the whole examined period with a maximum on
      the 14th day after irradiation. The effect of Broncho-Vaxom was less noticeable
      in the regenerating liver and appeared especially on the 7th day after
      irradiation.

PMID- 9595267
TI  - Testing of toxic and DNA-damaging effects of N-cyclohexylthiophthalimide (Duslin
      P) on hamster V79 cells.
AB  - N-cyclohexylthiophthalimide, commercial name Duslin P, at concentrations 0.5-2
      micrograms/ml inhibited proliferation of V79 cells and at concentrations > 2
      micrograms/ml acted cytotoxically. Inhibition of cumulative DNA synthesis
      correlated well with the deleterious effects of Duslin P on growth activity and
      plating efficiency. DNA synthesis was not renewed even 6 h after the treatment of
      cells. Alkaline elution of DNA of V79 cells treated with Duslin P did not confirm
      our expectation that this chemical compound has a DNA-damaging effect. Duslin P
      strongly inhibited protein synthesis at concentrations > 2 micrograms/ml. We
      suggest that the cytotoxic effects of Duslin P are not accompanied by any
      genotoxic effects.

PMID- 9595268
TI  - A novel monoclonal antibody specific for biliary glycoprotein (CD66a).

PMID- 9595269
TI  - New monoclonal antibodies to human leucocyte surface molecule CD2.

PMID- 9595270
TI  - Extracellular ATP: a growth factor for vascular smooth muscle cells.
AB  - 1. Extracellular adenosine triphosphate (ATP) is mitogenic for vascular smooth
      muscle cells (VSMC) and stimulates several events that are important for cell
      proliferation: DNA synthesis, protein synthesis, increase of cell number,
      immediate early genes, cell-cycle progression, and tyrosine phosphorylation. 2.
      Receptor characterization indicates mitogenic effects of both P2U and P2Y
      receptors. The P2X receptor is lost in cultured VSMC and is not involved. Several
      related biological substances such as UTP, ITP, GTP, AP4A, ADP, and UDP are also
      mitogenic. 3. Signal transduction is mediated via Gq-proteins, phospholipase C
      beta, phospholipase D, diacyl glycerol, protein kinase C alpha, delta, Raf-1,
      MEK, and MAPK. 4. ATP acts synergistically with polypeptide growth factors (PDGF,
      bFGF, IGF-1, EGF, insulin) and growth factors acting via G-protein-coupled
      receptors (noradrenaline, neuropeptide Y, 5-hydroxytryptamine, angiotensin II,
      endothelin-1). 5. The mitogenic effects have been demonstrated in rat, porcine,
      and bovine VSMC and cells from human coronary arteries, aorta, and subcutaneous
      arteries and veins. 6. The trophic effects on VSMC and the abundant sources for
      extracellular ATP in the vessel wall make a pathophysiological role probable in
      the development of atherosclerosis, neointima-formation after angioplasty, and
      possibly hypertension.

PMID- 9595271
TI  - Termination of acute-phase response: role of some cytokines and anti-inflammatory
      drugs.
AB  - 1. The acute-phase response is triggered by changes in intracellular mediators
      that activate stress-sensitive kinases and transcription factors controlling the
      synthesis of proinflammatory cytokines such as TNF-alpha, IL-1, IL-8 or IFN
      gamma. 2. Natural extinguishing of acute-phase response occurs due to short half
      lives of inflammatory mediators and production of anti-inflammatory cytokines
      such as IL-10, IL-4, IL-13, TGF-beta and some others. 3. Excess proinflammatory
      cytokines are removed by soluble cytokine receptors and receptor antagonists. 4.
      Synthesis of proinflammatory mediators and cytokines can be blocked by
      glucocorticoids, some nonsteroidal anti-inflammatory drugs suppressing
      cyclooxygenase and by specific inhibitors of cytokine induction. 5. The most
      promising approach in effective termination of acute-phase response appears to be
      a combined use of anti-inflammatory cytokines and specific drugs.

PMID- 9595272
TI  - Monoamine and iron-related toxicity: from "serotonin-binding proteins" to lipid
      peroxidation and apoptosis in PC12 cells.
AB  - 1. Monoamines do not form coordination bonds with a preformed iron-serotonin
      binding protein (SBP) complex, as initially believed. Instead, metals oxidize the
      monoamines either directly (manganese, copper) or by oxygen free radical
      formation (iron), the oxidation products bind covalently to SBP and the
      conjugates are able to undergo redox cycling. These interactions are denoted as a
      "molecular oxidative mechanism." 2. Dopamine in combination with iron induces
      lipid peroxidation and apoptosis in PC12 cells by a stress oxidative-Ca2+
      independent mechanism. 3. Dopamine-iron cytotoxicity may have relevance to an
      understanding of the mechanism by which dopaminergic neurons are eroded in some
      neurodegenerative disorders.

PMID- 9595273
TI  - Septic shock.
AB  - 1. Septic shock is still a major complication of patients in intensive care units
      (ICUs) and, therefore, a main goal of ICU-related research. 2. After the
      unsatisfying results of multicenter clinical trials in blocking proinflammatory
      mediators such as tumor necrosis factor and interleukin-1 or endotoxin itself,
      research has focused on other important members of the cytokine pathways--in
      particular, anti-inflammatory cytokines such as interleukin 10. Moreover, there
      is an increasing knowledge of intracellular activation and deactivation pathways,
      inaugurating the theoretical advantage to block, attenuate or manipulate the
      inflammatory response at an early stage of disease or in a more specific fashion.
      3. This review points out new developments in our understanding of the
      pathophysiology of septic shock and gives an example of a more recent approach in
      septic shock research--the heat shock response.

PMID- 9595274
TI  - Deformability and oxidant stress in red blood cells under the influence of
      halothane and isoflurane anesthesia.
AB  - 1. The effects of halothane and isoflurane anesthesia on red blood cell (RBC)
      deformability, lipid peroxidation and antioxidant enzymes were tested in rabbits.
      2. RBC transit time was significantly increased to 2.12 +/- 0.07 msec after 1-hr
      halothane anesthesia preceded by 6 mg/kg pentobarbital injections from 1.98 +/-
      0.07 msec preanesthesia value (p < 0.05). Thiobarbituric acid-reactive substances
      also were increased significantly, being 23.35 +/- 2.75 nmol/gHb and 33.11 +/-
      5.34 nmol/gHb before and after anesthesia, respectively (p < 0.05). 3. Under
      halothane anesthesia without prior pentobarbital injection or under isoflurane
      anesthesia with or without pentobarbital injection, no significant alterations
      were observed in these parameters. 4. RBC superoxide dismutase activity was
      decreased in the group anesthetized with the pentobarbital-halothane combination.
      The impaired RBC deformability and increased oxidant damage might be related to
      the free radical formation during the metabolism of halothane. Pentobarbital can
      potentiate this effect either by inducing cytochrome P-450 or by altering
      antioxidant defense. 5. Alterations in RBC mechanical properties may contribute
      to the tissue perfusion problems that develop after surgery under general
      anesthesia.

PMID- 9595275
TI  - Fish oil given by gavage increases lymphocyte proliferation and production of
      hydrogen peroxide by rat macrophages.
AB  - 1. The effect of fish oil (FO) administration by gavage (0.4% body weight) on
      macrophage and lymphocyte function was investigated in young male rats. The
      results were compared with those obtained by administration of soybean oil (SB)
      and cocoa butter (CB). 2. Lymphocyte proliferation was markedly increased by FO
      administration compared with control and other oils. 3. Macrophage phagocytosis
      capacity was not affected by FO, but it was increased by CB and SB. 4. The oils
      did not affect the production of O2.- but increased the production of H2O2 in the
      presence of PMA. 5. The administration of the oils did not markedly affect the
      activity of antioxidant enzymes in macrophages, except for a decrease in
      superoxide dismutase activity by FO.

PMID- 9595276
TI  - Long-lasting actions of Bay K 8644 on responses of guinea pig taenia coli.
AB  - 1. Bay K 8644, a dihydropyridine Ca2+ agonist, (10(-6) M), induced strong
      rhythmic contractions in taenia coli and induced a contracture after about 5.5 hr
      of the application. Increases in Bay K 8644 concentrations prolonged the period
      of rhythmic contractions and slowed the onset of the contracture. 2. Nifedipine,
      a dihydropyridine Ca2+ antagonist, inhibited the delayed contracture to Bay K
      8644 more than the initial rhythmic contractions. The contracture to Bay K 8644
      may be preferentially dependent on extracellular Ca2+ entry in comparison with
      the rhythmic contractions in taenia coli.

PMID- 9595278
TI  - Alpha 1-adrenergic and 5-HT2-serotonergic effects of some beta-alkoxy-beta
      phenylethylamines on isolated rat thoracic aorta.
AB  - 1. Ten racemic beta-alkoxy-beta-phenylethylamines were found to elicit
      concentration-dependent contraction of the isolated rat thoracic aorta with
      apparent pD2 values in the 4.56-6.76 range. With one exception, which produces
      the same maximal contraction (Emax) as serotonin (5-HT), the Emax values attained
      with these compounds are lower than those produced by either 5-HT or
      norepinephrine (NE). 2. Pretreatment with either prazosin or ketanserin (10(-8)
      M) leads in most cases to decreased Emax values and slopes in the dose-response
      curves. Apparent serotonergic (pD2S) and adrenergic (pD2A) pD2 values going from
      4.22 to 6.08 (pD2S) and from 3.87 to 5.27 (pD2A) were calculated from results
      obtained in the presence of prazosin or ketanserin, respectively. 3. In the 10(
      7)-10(-5) M range, and in contrast with the results obtained with the previous
      compounds, BON [(+/-)-2-(2,5-dimethoxy-4-nitrophenyl)-2-methoxy-ethylamine]
      behaves as an antagonist to both 5-HT and NE (apparent pA2 = 7.08 and 7.45,
      respectively) in this preparation.

PMID- 9595277
TI  - A neuropharmacological analysis of PTZ-induced kindling in mice.
AB  - 1. Glutamate seems to play a central role in epilepsy, and kindling is considered
      the most useful experimental model in revealing plastic changes associated with
      epileptic features. 2. The aim of this study was to optimize pentylenetetrazol
      (PTZ)-kindling conditions in mice and analyze glutamatergic changes associated
      with this phenomena. 3. A significant increase (85.7%) in seizuring animals was
      observed after four PTZ administrations, with all subjects presenting full
      seizures after five administrations. 4. PTZ kindling, but not acute seizure,
      significantly increased (169.8%) the specific binding of [3H]glutamate in the
      cerebral cortex. 5. The development of PTZ-induced kindling in mice was prevented
      by the coadministration of phenobarbital or diazepam. 6. This study indicates
      that mice can be used in a reliable model of PTZ-induced kindling and that, as in
      rats, the kindling increases the specific [3H]glutamate binding in the cerebral
      cortex, therefore allowing for screening new drugs that can interfere in the
      plastic changes believed to underlie epileptic phenomena.

PMID- 9595279
TI  - Effect of granisetron on morphine-induced analgesia in mice by formalin test.
AB  - 1. In this investigation, the influence of a selective 5HT3 antagonist,
      granisetron, on morphine-induced antinociception in the formalin test has been
      studied. There is evidence that the 5HT3 receptor system takes part in analgesic
      response. 2. Male albino mice weighing 22-27 g were used in the experiments. All
      drugs were administered 30 min before formalin injection. Comparison between
      groups was made by analysis of variance and then Newman-Keuls test. 3. Different
      doses of morphine (1.5-9.0 mg/kg) subcutaneously induced antinociception in both
      phases of the formalin test. 4. Coadministration of granisetron (0.1-10.0 mg/kg)
      intraperitoneally had no effect on morphine analgesia, but granisetron injection
      alone induced dose-dependent analgesia in both phases of the formalin test. 5.
      Results of this study suggest a role for a new selective 5HT3 antagonist in
      analgesia.

PMID- 9595280
TI  - Protective effect of the K+ channel opener KRN4884 on peripheral occlusive
      arterial disease in rats.
AB  - 1. The effect of the potassium channel opener KRN4884 on the peripheral arterial
      occlusion model induced by laurate was examined and compared with that of
      beraprost sodium and nilvadipine. 2. KRN4884 or beraprost sodium prevented
      macroscopic changes in the paw after the injection of laurate. In contrast,
      nilvadipine did not improve the lesions. 3. KRN4884 produced a dose-dependent
      increase in gastrocnemius blood flow in the chronic femoral artery-ligated rats.
      The effect of KRN4884 on the blood flow was stronger in the hypoxic muscle than
      in the normal muscle. 4. KRN4884 did not have a direct antiplatelet aggregation
      activity. 5. These findings suggest that KRN4884 is useful for the therapy of
      peripheral arterial occlusive disease and that the effect of KRN4884 is
      associated with an increase in blood flow in ischemic skeletal muscle.

PMID- 9595281
TI  - Decrease in erythrocyte:plasma lithium ratio by concurrent administration of
      psychotropic drugs and lithium in mice.
AB  - 1. Previous studies paying attention to concurrent use of lithium (Li+) with a
      neuroleptic were not done under constant and controlled conditions. We were
      therefore encouraged to do a prospectively controlled study, presuming constant
      relevant factors, on concomitant use of Li+ with neuroleptic as well as other
      psychotropic agents. 2. The effects of concurrent administration of
      chlorpromazine, haloperidol, imipramine and carbamazepine with Li+ on the
      erythrocyte:plasma Li+ ratio and the intraerythrocyte Li+ concentration were
      studied in mice by using a new, direct method of measuring erythrocyte Li+
      concentration. 3. All of the foregoing agents with the exception of carbamazepine
      were observed to significantly decrease the Li+ ratio. 4. Lack of any significant
      effect by carbamazepine on Li+ transport may be an indication of this drug's
      efficacy as a supplement in Li+ therapy of bipolar affective disorders. 5. The
      decrease in Li+ ratio observed with chlorpromazine, haloperidol and imipramine
      may be explained through the mechanism by which these drugs stabilize the cell
      membrane and consequently affect Li+ transport in erythrocytes. 6. Moreover, our
      study proves that, although the Li(+)-sodium countertransport mechanism does not
      exist in mice, the same interaction between Li+ and other psychotropic drugs is
      seen. It can be concluded that such interaction is not mediated through Li(+)
      sodium countertransport. 7. It is suggested that, with concurrent use of a
      psychotropic drug and Li+, the amount of intraerythrocyte Li+ concentration be
      measured, instead of relying on the plasma Li+ concentration alone.

PMID- 9595282
TI  - Pharmacological analysis of monoamine synthesis and catabolism in the scallop,
      Placopecten magellanicus.
AB  - 1. The efficacies of various agents that affect monoamine synthesis, oxidation
      and methylation were evaluated in the scallop, Placopecten magellanicus, through
      the use of high performance liquid chromatography with electrochemical detection.
      2. Central ganglia, labial palps and feet from animals bathed in 10(-5) M or 10(
      4) M alpha-methyl-p-tyrosine for 1 day followed by 3-6 day recovery in artificial
      sea water had significantly reduced concentrations of 3,4-dihydroxyphenylalanine,
      norepinephrine, epinephrine, dopamine and 3,4-dihydroxyphenylacetic acid. 3.
      Central ganglia, labial palps and feet from scallops incubated in 10(-5) M or 10(
      4) M para-chlorophenylalanine for 1 day followed by a 3-6 day wash in artificial
      sea water had significantly reduced concentrations of 5-hydroxytryptophan, 5
      hydroxytryptamine and 5-hydroxy-3-indoleacetic acid. 4. Monamine oxidase
      inhibitors (administered at 10(-4) M for 1 day followed by a 2-day recovery)
      significantly decreased the concentrations of 3,4-dihydroxyphenylalanine and 5
      hydroxy-3-indolacetic acid and increased the concentrations of their
      corresponding precursors in tissues. Deprenyl, a monoamine oxidase type B
      inhibitor, generally had more potent effects than pargyline, which inhibits
      monoamine oxidase type B and type A. Clorgyline, a monoamine oxidase type A
      specific inhibitor, showed few significant effects on the levels of the
      monoamines or their precursors or metabolites. 5. Bath application of 10(-4) M
      3,5-dinitrocatechol, a blocker of catechol-O-methyl transferase, resulted in
      significant decreases in the concentrations of normetanephrine and metanephrine
      in nervous and other tissues and increased the levels of their corresponding
      precursors, dopamine, norepinephrine and epinephrine. 6. Generally, treatments
      that appeared to directly cause changes in levels of catecholaminergic compounds
      indirectly resulted in inverse changes in levels of indolaminergic compounds, and
      vice versa. This suggests an interaction between these transmitter systems. 7.
      The detection of monoaminergic compounds and dramatic changes in their
      concentrations following various drug effects strongly suggests the presence of
      mammalian-type metabolic pathways leading to synthesis and subsequent
      inactivation of monoamines.

PMID- 9595283
TI  - The effects of epinine on arterial blood pressure and regional vascular
      resistances in anesthetized rats.
AB  - 1. We carried out experiments in anesthetized rats to study the hemodynamic
      effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg)
      produced a biphasic effect on mean arterial blood pressure (n = 30). At doses
      lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as
      21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much
      as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner
      (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the
      hypotensive effect of epinine but did not change the hypertensive effect. In the
      presence of prazosin (1,000 micrograms/kg), arterial blood pressure remained
      significantly decreased at all doses of epinine. Neither sulpiride nor prazosin
      changed the bradycardic effect of epinine. 3. Prazosin produced a significant
      decrease in renal vascular resistance. Epinine (5 micrograms/kg) after prazosin
      reverted the effects of prazosin in renal vascular resistance, without any
      significant modification in the renal blood flows. However, 20 micrograms/kg
      epinine increased the renal vascular resistances and, moreover, produced a
      significant decrease in the blood flows of both kidneys. Neither prazosin nor
      epinine produced modifications in the intestinal vascular bed. 4. Although
      epinine possesses significant dopamine and alpha-adrenergic activities that are
      involved in the biphasic effect of the agent on mean arterial blood pressure in
      anesthetized rats, in the presence of prazosin, it is not possible to manifest
      dopaminergic activity involved in the increase in renal or mesenteric blood flow;
      this may be due to the low tone of the vascular wall induced by the alpha
      adrenergic antagonist, though an alpha 2-activity cannot be discarded.

PMID- 9595284
TI  - Effects of GABAergic drugs on physostigmine-induced improvement in memory
      acquisition of passive avoidance learning in mice.
AB  - 1. The effect of gamma-aminobutyric acid (GABA) receptor agonists and antagonists
      on acquisition of a step-down passive avoidance learning in mice was measured in
      the presence and absence of physostigmine. 2. Intraperitoneal injection of
      different doses of the anticholinesterase drug physostigmine (0.1-0.3 mg/kg)
      increased acquisition in mice dose dependently. The maximum response was obtained
      with 0.3 mg/kg of the drug. Higher doses of the drug impaired acquisition of the
      learned response. To show the effect of the GABAergic system on acquisition,
      GABAA receptor agonists and antagonists were challenged against 0.2 mg/kg of
      physostigmine. 3. Administration of the GABAA receptor agonist muscimol but not
      the GABAB receptor agonist baclofen decreased the acquisition of the learned
      task. However, the improvement induced by physostigmine (0.2 mg/kg) was decreased
      by both muscimol and baclofen. A combination of both agonists caused a higher
      inhibitory effect on the physostigmine response. 4. Pretreatment of animals with
      the higher doses of GABAA receptor antagonists bicuculline and picrotoxin but not
      the GABAB receptor antagonist phaclofen impaired learning. Both the GABAA and
      GABAB receptor antagonists reduced the learning improvement induced by
      physostigmine. The inhibitory effects of the GABAA and GABAB receptor antagonists
      are lost when combined together. 5. Bicuculline, picrotoxin or phaclofen
      increased the impairment of learning induced by muscimol, whereas a combination
      of either of the antagonists with baclofen did not alter the learning. The GABAA
      antagonists reduced the inhibitory effect of muscimol, whereas a higher dose of
      phaclofen increased the inhibition of the physostigmine response induced by
      muscimol and baclofen on physostigmine-induced learning improvement. 6. Phaclofen
      decreased but a higher dose of bicuculline increased the baclofen-induced
      inhibition of physostigmine effect. 7. It is concluded that both GABAA and GABAB
      activation inhibit improvement of acquisition induced by physostigmine.

PMID- 9595286
TI  - Effects of spironolactone on exercise capacity and neurohormonal factors in
      patients with heart failure treated with loop diuretics and angiotensin
      converting enzyme inhibitor.
AB  - 1. Treatment with spironolactone is reported to be useful when combined with loop
      diuretics and an angiotensin-converting enzyme (ACE) inhibitor in severe
      congestive heart failure (CHF). However, the effects of the addition of
      spironolactone on exercise capacity and neurohormonal variables have not been
      demonstrated. This study determined the effects of additive spironolactone on
      exercise capacity and neurohormonal factors in patients with mild CHF. 2. Oxygen
      uptake (VO2), plasma norepinephrine (NE), renin activity (PRA), angiotensin II
      (AII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured at
      rest and after peak exercise in nine patients with CHF (six idiopathic and three
      ischemic cardiomyopathy; New York Heart Association (NYHA) classes II and III)
      who were already taking furosemide (mean 29 +/- 5 mg/day) and enalapril (mean 4.7
      +/- 0.8 mg/day). Studies were repeated after 16 weeks of treatment with additive
      single daily dose of 25 mg of spironolactone. In four of nine patients, the
      exercise test was repeated after a 4-weeks washout of spironolactone. 3.
      Treatment with spironolactone caused natriuresis, decreased cardiothoracic ratio
      in chest X-ray (before vs. after treatment: 53.7 +/- 1.2 vs. 50.7 +/- 1.4%, P <
      0.01), and improved NYHA functional class. Peak VO2 (17.1 +/- 1.6 vs. 17.5 +/-
      2.2 ml/min/kg, NS) and heart rate and blood pressure responses to exercise were
      not altered. Resting NE (215 +/- 41 vs. 492 +/- 85 pg/ml, P < 0.01) and resting
      PRA (8.2 +/- 2.3 vs. 16.2 +/- 4.1 ng/ml/hr, P < 0.01) as well as peak NE (1618 +/
      313 vs. 2712 +/- 374 pg/ml, P < 0.01) and peak PRA (12.8 +/- 3.2 vs. 28.1 +/-
      11.8 ng/ml/hr, P = 0.17) were augmented after additive spironolactone. ALD and
      AII were insignificantly increased, and ANP was insignificantly decreased at peak
      exercise after spironolactone treatment. Spironolactone washout was associated
      with a trend of the neurohormones to return toward pretreatment values. 4. In
      conclusion, chronic additive treatment with spironolactone was associated with
      neurohormonal activation both at rest and during exercise without changing the
      exercise capacity of patients with mild CHF who were already on loop diuretics
      and ACE inhibitor therapy.

PMID- 9595285
TI  - Hyperammonemia reduces water immersion--restraint stress gastric ulcers in rats.
AB  - 1. The influence of hyperammonemia (produced by the continuous intraperitoneal
      infusion of ammonium acetate for 6 days) on stress-induced gastric ulcer
      formation was investigated in conscious rats. 2. Continuous ammonium acetate
      infusion significantly reduced stress-induced gastric ulceration concomitant with
      an increase in gastric blood flow, as determined using radioactive microspheres.
      The serum levels of L-arginine as well as nitrite and nitrate (oxidative
      byproducts of nitric oxide) were increased by ammonium acetate infusion. 3. Prior
      administration of N omega-nitro-L-arginine methyl ester, a competitive nitric
      oxide synthase inhibitor, substantially attenuated the increase in gastric blood
      flow caused by ammonium acetate infusion and diminished the protective effect on
      gastric ulceration. 4. These findings suggest that the synthesis of endogenous
      nitric oxide from L-arginine is accelerated by continuous ammonium acetate
      infusion when the urea cycle remains intact and has a substantial cytoprotective
      effect on the stomach, probably through maintaining the gastric mucosal
      microcirculation.

PMID- 9595287
TI  - Contribution of nitric oxide and substance P to nonadrenergic, noncholinergic
      transmission in the guinea pig ileum.
AB  - 1. The possible contribution of the nonadrenergic noncholinergic (NANC)
      transmitters nitric oxide (NO) and substance P (SP) to the contractility of
      guinea pig isolated ileum was studied by the responses of the longitudinal muscle
      to electrical field stimulation (0.8 msec, 40 V, 1-20 Hz, 20 sec) of the
      intrinsic nerves and by the presence and distribution of NADPH-diaphorase- and SP
      positive nerve structures in the myenteric plexus. 2. The electrically elicited,
      tetrodotoxin (0.3 microM)-sensitive responses, in the presence of phentolamine (5
      microM), propranol (5 microM), and atropine (3 microM) consisted of relaxation,
      followed by twitch and tonic contraction on which phasic contractions were
      superimposed. 3. NG-nitro-L-arginine (L-NNA; 0.1 mM or 0.5 mM), an inhibitor of
      NO synthesis abolished the relaxation. L-arginine (0.1 mM), a substrate for NO
      synthesis, but not D-arginine, restored it. L-NNA concentration dependently
      increased the twitch and tonic contractions. Sodium nitroprusside (1 microM or 10
      (M), an exogenous donor of NO, was without effect on the electrically evoked
      responses. 4. AP 13.2 ACOH (AP; 0.1 microM or 10 microM), a blocker of SP
      receptors, frequency dependently inhibited or even prevented the twitch and tonic
      contractions. AP concentration-dependently increased the relaxation or reversed
      the responses to electrical stimulation into a deep relaxation. 5. The
      concentration-response curve for SP (1 nM-0.1 microM) was shifted to the right by
      AP, the EC50 values being 5.2 +/- 0.4 nM and 88.0 +/- 3.0 nM, respectively. The
      effects of SP were not altered by L-NNA (0.1 mM). 6. These findings, supported by
      morphological data about distribution of NADPH-diaphorase-positive nerve cell
      bodies and processes and SP-positive varicose fibers, suggest the contribution of
      NO and SP to NANC transmission. It appears that NO inhibits prejunctionally the
      SP transmission whereas SP counteracts the NO effect at the postjunctional level.

PMID- 9595288
TI  - The effect of Ba2+ on the nitrergic mechanism in the isolated frog lung
      preparation.
AB  - 1. The present study was undertaken to investigate effects of Ba2+ on the
      isolated frog lung strips depolarized by 20 mM K+ in Ca2+ free Ringer solution.
      2. Ba2+ produced monophasic relaxant response, whereas Ca2+ induced biphasic
      response consisting of a transient relaxation and a marked contraction. Both
      kinds of relaxation were inhibited completely by L-NOARG. L-arginine reversed the
      action of L-NOARG. 3. Ferrous sulfate, pyrogallol, hydroquinone, and vanadate
      reduced the Ba(2+)-induced relaxation in a concentration-dependent manner. 4.
      These findings suggest that Ba(+)-induced relaxation may fully be mediated by the
      nitrergic mechanism and the effect of Ba2+ on the nitric oxide synthase may be
      more selective than Ca2+.

PMID- 9595289
TI  - Investigation of the mechanisms underlying H2O2-evoked contraction in the
      isolated rat aorta.
AB  - 1. H2O2 (20-200 microM) elicited concentration-dependent contraction of rat
      isolated aortic rings. Pretreatment of the preparations with N-nitro-L-arginine
      (L-NNA) or removal of the endothelium augmented significantly the contractile
      response of rings to H2O2. The increase of the extracellular potassium
      concentration ([K+]o) resulted in a K(+)-dependent increase of the contractile
      response. 2. In Ca(2+)-free physiological salt solution (PSS), responses to H2O2
      were decreased approximately to 4% of the 100 mM KCl-induced response. 3. In
      addition, calcium channel blockers (nisoldipine, nifedipine, verapamil,
      flunarizine) did not completely inhibit H2O2-induced contractions. 4. H2O2-evoked
      contractions were abolished after repeated applications of caffeine or
      noradrenaline in Ca(2+)-free PSS. 5. Both extracellular Ca2+ entry through
      voltage-dependent Ca2+ channels and intracellular Ca2+ from caffeine- and
      noradrenaline-sensitive stores appear to participate in H2O2-induced contractions
      of rat aortic rings.

PMID- 9595291
TI  - The effect of isradipine on maximal electroshock seizures in mice.
AB  - 1. The aim of this study was to investigate the possible anticonvulsant effect of
      a dihydropyridine calcium antagonist, isradipine, which easily crosses the blood
      brain barrier displaying high affinity and specificity for the brain L-type
      voltage-sensitive calcium channel, on maximal electroshock seizures in mice. 2.
      Isradipine at i.p. doses of 2.5 mg/kg and 5.0 mg/kg was found to cause a
      statistically significant increase in the convulsion threshold of maximal
      electroshock seizures in a dose-dependent manner (P = 0.047 and P = 0.022,
      respectively). 3. It was concluded that the mode of action of the anticonvulsant
      effect of isradipine is related to blockade of the intraneuronal calcium
      currents, which play an important role in epileptic activity.

PMID- 9595290
TI  - Reversal of hypothermia-induced action potential lengthening by the KATP channel
      agonist bimakalim in isolated guinea pig ventricular muscle.
AB  - 1. ATP-sensitive potassium (KATP) channel openers shorten cardiac ventricular
      muscle action potential duration (APD), reduce resting and developed contractile
      force, and have been shown to provide cardioprotection when given before, during,
      and after either short-term ischemia or long-term hypothermia. The authors' aim
      was to determine the concentration-dependent effect of the potent KATP channel
      opener bimakalim on transmembrane action potential changes induced by mild (27
      degrees C) and moderate (20 degrees C) hypothermia in isolated guinea pig
      ventricular muscle. 2. Conventional microelectrode techniques were used to record
      action potentials (APs) in single myocytes during normothermia (37 degrees C) and
      hypothermia in the presence and absence of 0.1 to 30 mumol.l-1 bimakalim. 3.
      Hypothermia alone increased APD and depolarized the diastolic membrane potential
      (DMP): APD90 = 141.7 +/- 7.0 msec and DMP -86.2 +/- 1.4 mV (n = 6) at 37 degrees
      C versus 235.7 +/- 7.8 msec and -75.6 +/- 1.0 mV at 20 degrees C (n = 7). At 37
      degrees C, bimakalim (0.1-10 mumol.l-1) shortened APD in a concentration
      dependent fashion. 4. APD90 was markedly reduced from 141.7 +/- 7.0 msec without
      bimakalim to 9.5 +/- 2.6 msec with 10 mumol.l-1 bimakalim (n = 6); this effect
      was blocked by glibenclamide. DMP was hyperpolarized by bimakalim. More bimakalim
      was required to shorten APs during mild and moderate hypothermia. The 50%
      effective concentration (EC50) of bimakalim required to maximally shorten APD90
      was 0.96 +/- 0.10 mumol.l-1 at 37 degrees C; this increased to 3.96 +/- 0.24
      mumol.l-1 at 27 degrees C, and to 12.34 +/- 0.72 mumol.l-1 at 20 degrees C.
      Relative to hypothermia-induced depolarization, bimakalim hyperpolarized DMP
      toward drug-free values obtained at 37 degrees C. 5. These results indicate that
      hypothermia shifts the bimakalim concentration APD90 response curve to the right
      such that 13 times more bimakalim is required at 20 degrees C shorten APD by the
      same amount as at 37 degrees C. Bimakalim also reverses hypothermia-induced AP
      lengthening and tends to reverse the hypothermia-induced decrease in DMP. 6.
      These findings aid in our understanding of the cardioprotective effects of KATP
      channel openers during hypothermia.

PMID- 9595292
TI  - Effects of calcitonin and calcitonin gene-related peptide on the substance P
      mediated secretion of fluid from the rat submandibular gland.
AB  - 1. The effects of rat calcitonin gene-related peptide (rCGRP), rat calcitonin
      (rCT) and salmon calcitonin (sCT) on the substance P-mediated (SP-mediated)
      secretion of fluid from the rat submandibular gland were investigated. 2. Rat
      CGRP potentiated and prolonged the SP-mediated secretion of fluid from the rat
      submandibular gland in a dose-dependent manner. CGRP also enhanced methacholine-
      and phenylephrine-mediated secretion of fluid. 3. The potentiating effect of the
      combination of rCGRP and SP was somewhat reduced by pretreatment with spantide,
      human CGRP8-37 and atropine but not by pretreatment with phentolamine or with
      propranolol. 4. Salmon CT at a low dose mimicked the effect of rCGRP on the SP
      mediated secretion of fluid, but its potency was lower than that of rCGRP.
      However, rCT had no effect on the SP-mediated secretion of fluid. 5. These
      results suggest that the potentiating effects of rCGRP and SP might involve
      cholinergic receptors, as well as CGRP and tachykinin receptors, and that sCT,
      but not rCT, is able to mimic rCGRP in potentiating the secretion of fluid
      induced by SP.

PMID- 9595293
TI  - Effect of reactive oxygen species promoted by delta-aminolevulinic acid on
      porphyrin biosynthesis and glucose uptake in rat cerebellum.
AB  - 1. delta-Aminolevulinic acid (ALA) has been reported to promote reactive oxygen
      species (ROS). Overproduction and accumulation of ALA, as it occurs in acute
      intermittent porphyria (AIP), can be the origin of an endogenous source of ROS,
      which can then exert their oxidative damage to cell structures. 2. To investigate
      the induction of lipid peroxidation by ALA, thiobarbituric acid reactive
      substances and conjugated diene formation were measured by using minimal tissue
      units (MTUs) obtained from rat cerebellum. Malondialdehyde levels increased with
      ALA concentration and incubation time (72% at 1.0 mM ALA and 127% at 4.0 mM ALA
      for 4 hr), and conjugated diene formation was enhanced 50% in incubations with
      1.0 mM ALA for 4 hr. 3. ALA-promoted ROS by exposure of cerebellum MTUs to 1.0 mM
      ALA during different intervals (1-4 hr) was partly reduced by the addition of
      antioxidants such as superoxide dismutase (SOD; 50 U/ml), catalase (4.5 microM)
      and dimethylsulfoxide (150 mM), demonstrating the involvement of O2-., H2O2 and
      OH. in ALA autooxidation. 4. Porphobilinogen biosynthesis was 170% increased when
      cerebellum MTUs were incubated with 1.0 mM ALA for 4 hr in the presence of SOD,
      suggesting that protein damage was promoted by ALA autooxidation. 5. These
      findings provide the first experimental evidence of the involvement of ALA
      promoted ROS in the damage of proteins related to porphyrin biosynthesis,
      specially ALA-D. Oxidation of this enzyme would lead to further accumulation of
      ALA in AIP patients, which may be the origin of the well-known neuropsychiatric
      manifestations.

PMID- 9595295
TI  - Inhibition of the fast Na+ current by taurine in guinea pig ventricular myocytes.
AB  - 1. Effects of taurine on the fast Na+ current (INa) in isolated guinea pig
      ventricular cardiomyocytes were examined by using the whole-cell voltage-clamp
      method. Experiments were performed at room temperature (22 degrees C). 2. Test
      pulses were applied from -60 to +40 mV from a holding potential of -90 mV.
      Addition of taurine to the bath solution markedly inhibited the INa in a
      concentration-dependent manner; at -30 mV, by 39.0 +/- 4.1% (n = 8, P < 0.01) at
      10 mM and by 56.1 +/- 4.7% (n = 9, P < 0.001) at 20 mM. 3. Simultaneously, the
      time constant of inactivation phase for INa decreased to 0.95 +/- 0.4 ms (n = 8,
      P < 0.05) at 10 mM and to 1.02 +/- 0.3 ms (n = 9, P < 0.05) at 20 mM, from 1.29
      +/- 0.3 ms in normal Tyrode solution. 4. These results indicate that taurine
      inhibits the INa current, which would play an important role in the cell
      functions.

PMID- 9595294
TI  - Effect of vitamin E on vascular responses of thoracic aorta in rat experimental
      arthritis.
AB  - 1. Vascular contractile and relaxant responses were evaluated in isolated aortic
      rings of adjuvant-induced arthritic rats in comparison with control rats, and the
      effect of an antioxidant treatment on the development of the arthritis was
      investigated by vitamin E administration (100 mg/kg/day, i.m., for 26 days). 2.
      Arthritis was induced by an intradermal injection of Freund's complete adjuvant
      into rat paw. Vascular responses, arthritic lesions and serum copper levels were
      evaluated after 26 days from adjuvant inoculation. 3. Serum copper levels were
      significantly lower in arthritic rats than in the control. 4. The contractile
      response of aortic rings to phenylephrine (PE), but not to KCl, was increased in
      preparations from arthritic rats, which could be explained by an enhancement of
      intracellular calcium contents. 5. Acetylcholine (Ach)-mediated endothelium
      dependent and sodium nitroprusside (SNP)-mediated endothelium-independent
      relaxations were not changed significantly in vascular preparations from
      arthritic rats. 6. In arthritic rats, vitamin E treatment improved arthritic
      lesions with an increase in copper levels. Despite this ameliorating effect,
      vitamin E treatment caused an increase in contractile response to PE and a
      decrease in the relaxant response to Ach and SNP in arthritic rats. 7. These data
      show that vitamin E provides ameliorating effects in improving systemic signs of
      experimental arthritis, but it fails to restore abnormalities in vascular
      function, indicating that adjuvant-induced alterations in vascular function may
      include mechanisms other than oxygen-free radical formation.

PMID- 9595296
TI  - Localization and pharmacological characterization of [3H]perospirone-binding
      sites in rat brain.
AB  - 1. The regional distribution and pharmacological property of binding sites for
      perospirone, an atypical neuroleptic, in rat brain were examined by an in vitro
      binding assay. 2. A high degree of [3H]perospirone binding was observed in the
      frontal cortex, caudate putamen, nucleus accumbens, olfactory tubercle, lateral
      septum, choroid plexus, hippocampus and entorhinal cortex. 3. In cortical
      membranes, the frontal cortex and nucleus accumbens, 1 nM [3H]perospirone bound
      predominantly to serotonin 5-HT2A receptors (about 40% of specific
      [3H]perospirone binding) rather than to dopamine D2 receptors. 4. About 60% of
      binding sites specifically labeled with 1 nM [3H]perospirone were D2 receptors
      and about 20% were 5-HT2A receptors in striatal membranes and the caudate
      putamen. 5. [3H]Perospirone interacted mainly with 5-HT1A receptors in
      hippocampal membranes and the lateral septum. 6. These results suggest that
      perospirone has a broad binding activity and that predominant occupancy of 5-HT2A
      receptors in mesocortical and mesolimbic structures might concern the atypical
      profile of perospirone as an antipsychotic drug.

PMID- 9595297
TI  - Effect of EPC-K1 on myocardial infarct size in a rat model with coronary artery
      occlusion and reperfusion.
AB  - 1. The ability of EPC-K1 to improve myocardial infarction was evaluated in a rat
      model with coronary artery occlusion and reperfusion. 2. The myocardial infarct
      size was 30.5 +/- 1.7% by intravenous (i.v.) administration and 28.8 +/- 2.7% by
      intraduodenal (i.d.) administration of the saline EPC-K1 at doses between 1 and
      10 mg/kg, i.v. and at doses between 50 and 200 mg/kg, i.d., reduced myocardial
      infarct size dose dependently. Significant reduction in myocardial infarct size
      was found at a dose of 10 mg/kg, i.v., and 200 mg/kg, i.d.

PMID- 9595298
TI  - Antiestrogenic compounds inhibit estrogen induced expressions of basic fibroblast
      growth factor and its mRNA in well-differentiated endometrial cancer cells.

PMID- 9595299
TI  - Morphological aspects of the median eminence--place of accumulation and secretion
      of regulatory neurohormones and neuropeptides.
AB  - The median eminence (ME) is a small brain area forming both the structural and
      functional bridge between the hypothalamus and the hypophysis. It is supplied by
      a variety of neurohormones and neuropeptides which are delivered to the ME by
      different hypothalamic and extrahypothalamic pathways. These biologically active
      substances may act in the ME locally influencing the activity of secretion of the
      neighbouring terminals or, after being released from the neuronal endings into
      the network of fenestrated capillaries and transported to the hypophysis, they
      may be involved in the regulation of secretion of adenohypophyseal hormones.
      Recent demonstrations of extensive colocalizations of these biologically active
      substances in individual axonal endings in the ME with wide spectrum of
      biological actions further emphasizes the ME as an important place involved in
      the neuroendocrine regulatory processes.

PMID- 9595300
TI  - Cooperative dynamics of quasi-1D lipid structures and lateral transport in
      biological membranes.
AB  - A model for the dynamics of quasi-1D lipid structures in biological membranes is
      proposed. The model takes into account interactions between the lipid heads and
      hydro-carbon chains, the description of their relaxation dynamics being based on
      the phenomenological Ginzburg-Landau approach. It is shown that in lateral linear
      structures of lipids, a soliton-like excitation can propagate with constant
      velocity. The latter in turn may provide for lateral transport of matter and for
      membrane conformation changes.

PMID- 9595301
TI  - Potential cancerostatic benfluron is metabolized by peroxidase: in vitro
      biotransformation of benfluron by horseradish peroxidase.
AB  - Horseradish peroxidase (HRP) was used to investigate whether benfluron (a
      potential cytostatic drug) can be biotransformed extra-hepatically by systems
      other than flavin-containing monooxygenase and cytochromes P450. Three types of
      incubation mixtures differing in buffers (Na-phosphate buffer 50 mmol/l, pH 6.8
      and 8.4 and Tris-HCl buffer 25 mmol/l, pH 7.5) were tested. The amount of N
      demethylated benfluron (demB) formed was significantly higher (up to 4 times in
      the Na-phosphate buffer, pH 8.4, and 5 times in the Na-phosphate buffer, pH 6.8,
      and in the Tris-HCl buffer, pH 7.5) compared to control experiments. The highest
      yields of demB were obtained with the moderately alkaline Na-phosphate buffer (50
      mmol/l, pH 8.4). The concentration of demB increased during thirty minutes of
      incubation, and then remained constant through the end of two-hour incubation.
      The results support the hypothesis that benfluron can be metabolized extra
      hepatically by N-demethylation reaction catalyzed by peroxidases.

PMID- 9595302
TI  - Mitochondrial contact sites detected by creatine phosphokinase activity in the
      hearts of normal and diabetic rats: is mitochondrial contact sites formation a
      calcium-dependent process?
AB  - Mitochondrial contact sites (MiCS) are structures in the mitochondrial membrane
      containing the structure-bound mitochondrial isoenzyme of creatine phosphokinase
      that participates in the transfer of energy into the cytoplasm. This explains the
      increased formation of MiCS found in hearts with high metabolic activity. Earlier
      we demonstrated that enhanced MiCS formation may also be induced by perfusing the
      heart with increased, but still not cardiodepressive concentrations of Ca2+ (2.2
      mmol.l-1) in the perfusate. Nevertheless, neither the molecular mechanism by
      which Ca2+ ions may induce an increase in MiCS formation, nor the dependence of
      Ca(2+)-induced MiCS formation on the intracellular Ca2+ level have yet been
      elucidated. In the present study we investigated the effect of Langendorff
      perfusion with 2.2 mmol.l-1 Ca2+ on formation of MiCS in normal as well as in
      diabetic hearts. The latter, namely, are characterized by altered metabolism as
      well as Ca(2+)-handling, resulting in elevated [Ca2+]i. We have found that the
      amounts of MiCS in diabetic hearts outnumbered those in normal hearts. Our
      results showed that in comparison to perfusion with 1.6 mmol.l-1 Ca2+ a perfusion
      with 2.2 mmol.l-1 Ca2+ is capable of significantly increasing (p < 0.01) the
      formation of MiCS in control hearts. In both groups of diabetic hearts the
      numbers of MiCS were significantly increased in comparison to healthy controls (p
      < 0.01). Moreover, no significant differences in amounts of MiCS were found
      between healthy hearts perfused with 2.2 mmol.l-1 Ca2+ and diabetic hearts of
      both groups (p > 0.05). In diabetic hearts, MiCS formation in response to [Ca2+]e
      was little manifested. Our results also confirmed that elevated [Ca2+]i in all
      cases represented a signal for increased formation of MiCS in the heart.

PMID- 9595303
TI  - Ca(2+)-activated K+ channel and the activation of Ca2+ influx in vanadate-treated
      red blood cells.
AB  - The mechanism by which K+ inhibits vanadate-induced 45Ca2+ influx by human red
      blood cells (RBC) was studied using several independent approaches. The following
      results were found: 1. The inhibitory effect of K+ was absent when RBC were
      loaded with a Ca(2+)-chelator. This treatment at the same time inhibited the
      vanadate-induced K+ efflux, and the membrane hyperpolarization induced by Ca2+ in
      vanadate-treated cells. 2. The potency of K+, Rb+, and Cs+ to inhibit vanadate
      induced Ca2+ influx corresponded to their ability to depolarize the RBC membrane
      via the Ca(2+)-activated K+ channel (K(Ca)). 3. Inhibition of the vanadate
      induced 45Ca2+ influx by a protonophore proceeded in parallel with the inhibition
      of the vanadate-plus-Ca(2+)-induced membrane hyperpolarization. 4. Valinomycin in
      part released the inhibition of the vanadate-induced Ca2+ influx by known K(Ca)
      inhibitors (quinine, oligomycin, 4-aminopyridine) but not by inhibitors of the
      Ca2+ channel (Cu2+, HS-reagents, organic Ca2+ channel blockers). 5. K+ did not
      inhibit the vanadate-induced Ca2+ influx in dog RBC which have K(Ca) but no
      transmembrane K+ gradient. The inhibition of the vanadate-induced Ca2+ influx by
      external K+ appears to be due to the elimination of the electrical component of
      the Ca(2+)-motive force imposed by opening of the K(Ca). This implies that the
      Ca2+ carrier mediating the influx of Ca2+ in the presence of vanadate is of
      uniport type, and that the activity of K(Ca) may serve as a supporting element
      for Ca2+ influx.

PMID- 9595304
TI  - Vanadate changes Ca2+ influx pathway properties in human red blood cells.
AB  - The properties of the basal Ca2+ influx (measured using cells labelled with
      45Ca2+) in intact human red blood cells (RBC) were compared with those of 45Ca2+
      influx induced by vanadate. The basal Ca2+ influx was not sensitive to inhibitors
      of vanadate-induced Ca2+ influx such as the HS-reagent p-chloromercuribenzoate
      and low concentrations of Cu2+, and also the sensitivity to nifedipine was
      significantly weaker. High K+ known to suppress vanadate-induced 45Ca2+ influx
      had no effect on the basal Ca2+ influx. Both processes were saturated with Ca2+
      but the latter was saturated at higher Ca2+ concentrations (KM(Ca) 2.1 vs. 0.5
      mmol/l). These experiments favour the notion that vanadate changes the properties
      of the inward-directed Ca(2+)-transport pathway in human RBC membrane. Vanadate
      induced 45Ca2+ influx was insensitive to pertussis toxin and cholera toxin, and
      several non-steroidal antiinflammatory agents did not influence it in a
      consistent manner. Li+ partly inhibited the 45Ca2+ uptake. Vanadate stimulated
      the incorporation of 32P(in) into PIP2 in human but not in pig RBC which are
      known to be defective in the phosphoinositide metabolism and in the vanadate
      induced 45Ca2+ uptake. These results suggest that the change in the Ca2+ influx
      pathway properties induced by vanadate may involve changes in the metabolism of
      phosphoinositides but not of the arachidonate metabolism nor G-protein
      activation.

PMID- 9595305
TI  - Localization of the Ca(2+)-binding S100A1 protein in slow and fast skeletal
      muscles of the rat.
AB  - The distribution of S100A1 in rat soleus and EDL muscles was studied
      immunocytochemically at the ultrastructural level using immunogold as marker.
      Antigens were localized mainly in myofibrils at all levels of the sarcomere.
      Immunogold particles along myofibrils were not uniformly distributed. The highest
      density of particles was found at Z-lines. An increase in particle density was
      observed in the middle of half A-bands in EDL and in the middle of half I-bands
      in the soleus. Antigen sites were also present at M-lines and at distinct
      locations of the sarcoplasmic reticulum.

PMID- 9595306
TI  - [Prednicarbate--the epidermis-corticoid among the topical corticoids].

PMID- 9595308
TI  - Community orientation in health services organizations: the concept and its
      implementation.
AB  - The management of community health needs has become a focal point in the drive to
      contain health care costs, enhance service quality, and improve access to care.
      This article presents a concept of community orientation that health services
      organizations can use to provide community-focused care. It also discusses the
      organizational antecedents and consequences of community orientation in health
      services organizations and develops research propositions.

PMID- 9595307
TI  - Competitive forces in the medical group industry: a stakeholder perspective.
AB  - Applying Porter's model of competitive forces to health care, stakeholder
      concepts are integrated to analyze the future of medical groups. Using both
      quantitative survey and qualitative observational data, competitors, physician
      suppliers, integrated systems new entrants, patient and managed care buyers, and
      hospitals substitutes are examined.

PMID- 9595309
TI  - The challenges of governing public-private community health partnerships.
AB  - This article identifies key challenges that arise in governing public-private
      partnerships designed to improve community health status. Using telephone
      interview and focus group data, we describe how the 25 public-private community
      health partnerships participating in the Community Care Network (CCN)
      Demonstration Program grapple with three interrelated clusters of governance
      issues: turf, community accountability, and growth and development.

PMID- 9595310
TI  - Can ethical management and managed care coexist?
AB  - The growth of for-profit managed care organizations raises serious ethical
      questions for managers in these settings, such as whether contemporary business
      ethics are most appropriate for health care organizations or how the principles
      of biomedical ethics can be integrated into profit-seeking firms. A model is
      proposed that seeks to consolidate both business ethics and biomedical ethics
      into a form that is useful to health service managers.

PMID- 9595311
TI  - A practical method of adjusting for risk in the prospective costs of capitated
      systems.
AB  - Increasingly, providers of health services and medical groups are required to
      negotiate with managed care organizations and evaluate the adequacy of capitation
      rates. An intelligent assessment of the rate of payment requires an accurate
      projection of the costs per member per month that have been adjusted for the risk
      present in the insured population. This article develops a practical model for
      incorporating risk in forecasts of the full cost per member per month.

PMID- 9595312
TI  - The organizational structure of medical group practices in a managed care
      environment.
AB  - This article analyzes the organizational structures of 155 medical group
      practices providing services in the highly competitive managed care environment
      in the upper midwest. The structure of the group practices and the methods of
      physicians' payment are analyzed in terms of the proportion of revenue obtained
      from financial risk-sharing managed care payment systems and the length of time
      involved with those systems.

PMID- 9595313
TI  - Infusion pump analyzers.
AB  - Infusion pump analyzers are test devices that aid in determining the performance
      of infusion pumps. These devices perform simple flow tests, and in some instances
      volume and occlusion pressure tests as well, that otherwise would be performed
      using burettes or other calibrated glassware, balances, timers, and pressure
      meters or gauges. We evaluated five models from four different suppliers,
      focusing primarily on performance and human factors design. Three units were
      rated Acceptable, and two were rated Acceptable--Not Recommended because of
      performance limitations and, for one of the units, poor human factors. This
      Evaluation includes an overview of infusion pump analyzer technology and a
      Selection Guide detailing the factors that facilities should consider when
      purchasing an infusion pump analyzer. In addition, a supplementary article
      discusses recertification systems, which are designed for testing home-use pumps
      before use on each new patient. Another supplementary article deals with trumpet
      curves, a capability that may have limited value for most users.

PMID- 9595314
TI  - Infusion pump inspection frequencies. How often is inspection really needed?
AB  - As noted in this issue's Evaluation of infusion pump analyzers, the frequency at
      which a facility inspects its infusion pumps can help determine its need for one
      or more analyzers. It can also have a financial impact on the clinical
      engineering department. In this article, we discuss inspection issues affecting
      infusion pumps, including our recommendations and how facilities can set
      intervals for their equipment. (For ECRI's procedure for inspecting infusion
      devices, refer to Procedure/Checklist 416-0595 in the Health Devices Inspection
      and Preventive Maintenance [IPM] System; contact ECRI's Communications Department
      at [610] 825-6000, ext. 888, for more information about this publication.)

PMID- 9595316
TI  - MediVators Endoscope Disinfector does not alarm for disinfection failures caused
      by blown fuse.

PMID- 9595315
TI  - General-purpose infusion pumps.
AB  - General-purpose infusion pumps deliver liquid medications to patients through
      intravenous or epidural routes at specified flows. They are most often used in
      hospitals and alternative care settings (e.g., physician' offices, patients'
      homes) when liquid medications need to be administered with greater accuracy or
      at higher flows than can be provided through a manually adjusted gravity
      administration set. In this Update of our February 1997 Evaluation of infusion
      pumps (Health Devices 26[2]), we tested 3 additional pumps from 3 suppliers. We
      also rated and ranked them in comparison with the 16 units from the February 1997
      study that are still being produced. With a few exceptions, we tested the new
      pumps against the same criteria and using the same test methods as those in the
      previous Evaluation. However, for this Update, the focus of our findings has
      broadened: although we continue to place strong emphasis on the pumps' protection
      against gravity free-flow, we also give significant weight to their overall
      safety, performance, and human factors design. As a result, our ratings and
      rankings scheme has changed, affecting the rankings of some of the previously
      evaluated units. Of the 19 currently available units that have been evaluated to
      date, we rated 13 units Acceptable, with 5 of those units ranked above the other
      8. A further 5 units were rated Conditionally Acceptable; we consider them
      Acceptable if they are used with the available free-flow protection. And 1 unit
      had performance problems that caused us to rate it Unacceptable (this unit has
      been recalled by its supplier; see the inset on page 162). As always, we caution
      readers not to base selection and purchasing decisions on our conclusions alone,
      but on a thorough understanding of the issues behind those conclusions, which can
      be gained by reading this Evaluation in its entirety and carefully reviewing the
      February 1997 issue.

PMID- 9595317
TI  - Reducing the risk of power loss to critical equipment.

PMID- 9595318
TI  - Temperature controller failure of a Chattanooga group hot-pack heating unit.

PMID- 9595320
TI  - Melting of Beckman GPR centrifuge fuse holders.

PMID- 9595319
TI  - Proper drain maintenance needed to save repair costs in Sorvall Cellwasher CW-2
      centrifuges.

PMID- 9595321
TI  - Desk cleaning.

PMID- 9595322
TI  - Could injury risk be predetermined?

PMID- 9595323
TI  - Injury prevention in practice.

PMID- 9595324
TI  - Randomised controlled trials in general practice: time for international
      collaboration.

PMID- 9595325
TI  - Going international: what are the implications?

PMID- 9595326
TI  - Children's views of accident risks and prevention: a qualitative study.
AB  - OBJECTIVES: To examine children's accounts of injury risks and opportunities for
      prevention. SETTING: Schools, youth clubs, and a holiday activity scheme in the
      south east of England. METHODS: Sixteen focus groups were held with 7-11 year old
      children. Transcripts of the discussions were analysed using qualitative methods.
      RESULTS: Children were knowledgeable about injury risks and how to reduce them.
      They also saw injury prevention as primarily their own responsibility. However,
      they were also sophisticated in their criticisms of generalised prevention
      advice, and evaluated safety messages in the light of local environmental and
      social knowledge. Personal experience was more often reported as a reason for
      risk reduction than formal prevention advice. Risks for injury were not isolated
      from other risks faced. CONCLUSIONS: Effective educational interventions aimed at
      changing children's risk behaviour should build more on children's own competence
      and knowledge of their local environment, and stress the need to manage risks
      rather than avoid dangers.

PMID- 9595327
TI  - School based bicycle safety education and bicycle injuries in children: a case
      control study.
AB  - OBJECTIVES: To evaluate possible benefits of a school based bicycle safety
      education program ("Bike Ed") on the risk of bicycle injury in children. METHODS:
      A population based case-control study was undertaken in a region of Melbourne,
      Australia. Cases were children presenting at hospital emergency departments with
      injuries received while riding bicycles. Controls were recruited by calling
      randomly selected telephone numbers. Data were collected by personal interview.
      RESULTS: Analysis, based on 148 cases and 130 controls aged 9 to 14 years, showed
      no evidence of a protective effect and suggested a possible harmful effect of
      exposure to the bicycle safety course (odds ratio (OR) 1.64, 95% confidence
      interval (CI) 0.98 to 2.75). This association was not substantially altered by
      adjustment for sex, age, socioeconomic status, and exposure, measured as time or
      distance travelled. Subgroup analysis indicated that the association was
      strongest in boys (OR 2.0, 95% CI 1.1 to 3.8), younger children, children from
      families with lower parental education levels, and children lacking other family
      members who bicycle. CONCLUSIONS: It is concluded that this educational
      intervention does not reduce the risk of bicycle injury in children and may
      possibly produce harmful effects in some children, perhaps due to inadvertent
      encouragement of risk taking or of bicycling with inadequate supervision.

PMID- 9595328
TI  - Comparison of community based smoke detector distribution methods in an urban
      community.
AB  - OBJECTIVES: Various methods of soliciting participation for a large smoke
      detector giveaway program were tested to determine the most effective method of
      distributing smoke detectors to a high risk urban population. SETTING: The target
      area was a 24 square mile (62 km2) section on the south side of Oklahoma City
      where 16% (73,301) of the city's population resided in 16% (34,845) of the
      dwellings (excluding apartments). Of the 66 persons in Oklahoma City who were
      injured in residential fires from September 1987 to April 1990, 45% (30) were in
      the target area. Of the target area injuries, 47% resulted from fires started by
      children playing with fire (fireplay). METHODS: The number of homes without
      detectors was estimated by telephone survey. Four different methods of soliciting
      participants were used, including notifying residents by mail; placing flyers on
      the doors of every habitable residence; and displaying flyers at public places
      (grocery stores, convenience stores, restaurants, etc). Each of these methods
      alerted residents that free smoke detectors were available at specific fire
      stations. The fourth method was distributing detectors door-to-door (canvassing).
      RESULTS: The canvassing method resulted in significantly more smoke detectors
      being distributed to homes without detectors (107%) than any of the three other
      methods (18%) (p < 0.00001). The canvassing method distributed detectors to 31%
      of the total target homes, compared with 5% with the other methods (p < 0.00001).
      Canvassing also resulted in the lowest estimated cost per detector distributed
      ($1.96) (all other methods, $3.95), and in the largest number distributed per
      volunteer hour (5.9 v 3.1 detectors per hour by other methods). CONCLUSIONS:
      Distributing smoke detectors directly to homes (canvassing) was the most
      effective and cost efficient method to reach high risk urban residents.

PMID- 9595329
TI  - Demographic risk factors for injury among Hispanic and non-Hispanic white
      children: an ecologic analysis.
AB  - OBJECTIVES: To determine the effects of neighborhood levels of poverty, household
      crowding, and acculturation on the rate of injury to Hispanic and non-Hispanic
      white children. SETTING: Orange County, California. METHODS: An ecologic study
      design was used with census block groups as the unit of analysis. Measures of
      neighborhood poverty, household crowding, and acculturation were specific to each
      ethnic group. Poisson regression was used to calculate mutually adjusted
      incidence rate ratios (IRRs) corresponding to a 20% difference in census
      variables. RESULTS: Among non-Hispanic white children, injury rates were more
      closely associated with neighborhood levels of household crowding (adjusted IRR
      2.36, 95% confidence interval (CI) 1.22 to 4.57) than with neighborhood poverty
      (adjusted IRR 1.06, 95% CI 0.89 to 1.26). For Hispanic children, the strongest
      risk factors were the proportion of Hispanic adults who spoke only some English
      (compared with the proportion who spoke little or no English, adjusted IRR 1.26,
      95% CI 1.04 to 1.53) and the proportion who were US residents for < 5 years
      (adjusted IRR 1.20, 95% CI 1.001 to 1.43). Neighborhood levels of household
      crowding were not related to injury among Hispanic children (adjusted IRR 0.98,
      95% CI 0.89 to 1.08), but surprisingly, neighborhood poverty was associated with
      lower injury rates (adjusted IRR 0.89, 95% CI 0.81 to 0.97). CONCLUSIONS:
      Cultural and geographic transitions, as well as socioeconomic differences, appear
      to contribute to differences in childhood injury rates between ethnic groups.

PMID- 9595330
TI  - A case-control study of risk factors for playground injuries among children in
      Kingston and area.
AB  - OBJECTIVE: To determine the risk for injury associated with environmental hazards
      in public playgrounds. SETTING: One hundred and seventeen playgrounds operated by
      municipalities or school boards in and around Kingston, Ontario, Canada. METHODS:
      A regional surveillance database was used to identify children presenting to
      emergency departments who were injured on public playgrounds; each case was
      individually matched (by sex, age, and month of occurrence) with two controls-
      one non-playground injury control, and one child seen for non-injury emergency
      medical care. Exposure data were obtained from an audit of playgrounds conducted
      using Canadian and US safety guidelines. Exposure variables included the nature
      of playground hazards, number of hazards, frequency of play, and total family
      income. No difference in odds ratios (ORs) were found using the two sets of
      controls, which were therefore combined for subsequent analysis. RESULTS:
      Multivariate analysis showed strong associations between injuries and the use of
      inappropriate surface materials under and around equipment (OR 21.0, 95%
      confidence interval (CI) 3.4 to 128.1), appropriate materials with insufficient
      depth (OR 18.2, 95% CI 3.3 to 99.9), and inadequate handrails or guardrails (OR
      6.7, 95% CI 2.6 to 17.5). CONCLUSION: This study confirms the validity of
      guidelines for playground safety relating to the type and depth of surface
      materials and the provision of handrails and guardrails. Compliance with these
      guidelines is an important means of preventing injury in childhood.

PMID- 9595331
TI  - All terrain vehicle ownership, use, and self reported safety behaviours in rural
      children.
AB  - OBJECTIVES: To describe all terrain vehicle (ATV) ownership, access, use, and
      safety behaviours in rural Manitoba children. METHODS: Questionnaire administered
      to a convenience sample of grade 6 students attending an agricultural fair.
      RESULTS: 162 grade 6 children participated. The mean age was 11.4 years, and 46%
      were male. 125 students (77%) reported having access to ATVs, including 69 four
      wheeled, 24 three wheeled, and four both three and four wheeled ATVs. ATV
      experience was reported in 95 students, significantly more often in males and
      among those with a family owned ATV, with no difference between children living
      on a farm and in a town. Use of helmets and protective clothing was inadequate
      (10-40%), and dangerous riding habits common, with males and children living on a
      farm reporting significantly fewer desirable behaviours. CONCLUSIONS: ATVs are
      commonly used by children in rural Manitoba, with inadequate protective gear and
      dangerous riding habits. Mandatory rider training, consumer and dealer education,
      and legislation enforcement could improve ATV safety in this population.

PMID- 9595332
TI  - Injury surveillance in accident and emergency departments: to sample or not to
      sample?
AB  - OBJECTIVES: To establish whether injury surveillance based on sampling strategies
      is as valid as total patient surveillance. METHODS: Canadian Hospitals Injury
      Reporting and Prevention Program (CHIRPP) data for 1996 were retrospectively
      analysed using five sampling frames. Proportions for key variables were
      calculated for each sample, then compared with the proportions for the total
      population of patients. RESULTS: Two of the five sampling frames produced
      statistically significant differences from the total population, which can be
      explained by seasonal variations. However, no significant differences were
      observed between the remaining three samples and the total population.
      CONCLUSIONS: A well planned and executed sampling strategy can generate as valid
      data as total patient surveillance, obviating the need for data collection on
      every patient presenting with an injury or poisoning. In practice, however,
      systematic sampling can be difficult to implement and sustain, counterbalancing
      the economic advantages.

PMID- 9595333
TI  - ANOVA, t tests, and linear regression.

PMID- 9595334
TI  - Case series and exposure series: the role of studies without controls in
      providing information about the etiology of injury or disease.
AB  - Descriptions of exposure histories in persons with the same injury or illness
      ("case series"), and descriptions of outcomes in persons with the same exposure
      ("exposure series"), have the potential to contribute knowledge relevant to
      disease etiology in some special situations. The case series can be thought of as
      a primitive form of case-control study--one in which the controls are only
      implied. Similarly, the exposure series is a rudimentary type of cohort study. By
      keeping these analogies in mind, those who author or read studies without
      controls can assess the design or results for selection bias, confounding, or
      information bias. While studies without controls cannot supplant true case
      control or cohort studies, they are relatively cheap and easy to perform, and
      there are circumstances in which they provide valuable information. Attention to
      design is needed to strengthen the results they provide.

PMID- 9595335
TI  - Community based intervention on adolescent risk taking: using research for
      community action.
AB  - OBJECTIVES: To use research on adolescent risk taking behaviour as an impetus for
      a community to develop locally based injury prevention strategies. DESIGN: Case
      study, based on a community action model and formative evaluation. This involved:
      a community profile on adolescent risk taking behaviour; interviews with service
      providers; dissemination of research findings to local policy makers; development
      and implementation of a community action plan to address adolescent risk taking;
      and assessment of its impact. SETTING: A rural town with a population of 10,195
      situated in the North Island of New Zealand. SUBJECTS: School aged adolescents
      and the safety policies and practices of community organisations involved with
      adolescents. RESULTS: Risk taking behaviours identified by the community profile
      included: drink-driving, substance abuse, carrying of weapons with intent to
      harm, and suicidal ideation. Community members identified that risk taking
      behaviour associated with alcohol in relation to: (1) violence (self directed and
      assault) and (2) road related injuries should be the focus of their activities.
      The strategies identified focused on advocacy, education, legal/regulatory
      change, and environmental modification. Evaluation conducted six months after
      intervention identified increased community awareness of the adverse effects of
      adolescent risk taking and some changes in policies and practice related to
      adolescent safety. CONCLUSIONS: Providing a community with local information that
      has high relevance for its members may act as a stimulus for the development of
      injury prevention initiatives. While this case study illustrated that a
      comprehensive approach focusing on adolescent risk taking behaviour, rather than
      on isolated injury problems, may be an appropriate way to highlight escalating
      adolescent injury rates, it also demonstrates the limitations of a short time
      frame for a community development project.

PMID- 9595336
TI  - Children and personal watercraft: injury characteristics and potential
      countermeasures.

PMID- 9595337
TI  - Safe Child Penarth: experience with a Safe Community strategy for preventing
      injuries to children.
AB  - OBJECTIVES: To evaluate the process of establishing a Safe Community project for
      children. DESIGN: A descriptive study. SETTING: Penarth, a town (population
      20,430) Vale of Glamorgan, South Wales. SUBJECTS: 3943 children and their
      families in Penarth. MAIN OUTCOME MEASURES: Whether the 12 criteria for a Safe
      Community project (World Health Organisation) were met. Implementation of the
      safety agenda set by the community. RESULTS: Safe Child Penarth met 10 of the 12
      criteria for the Safe Community network. All the items on the agenda were
      introduced in the initial two years of the project. There were difficulties,
      however, achieving sustained community ownership of the project. CONCLUSIONS: The
      Safe Community concept stimulated work to improve child safety in Penarth.
      Community safety initiatives should involve all local agencies to identify the
      problems and work with the community to set and meet the safety agenda.
      Partnership with the local authority is valuable to improve the safety of the
      environment. The experience generated from Safe Child Penarth has been used to
      develop a county wide, all age community safety project.

PMID- 9595338
TI  - Accidents among children under two years of age in Great Britain. 1950.

PMID- 9595339
TI  - Fatal and non-fatal farm injuries.

PMID- 9595340
TI  - A history of medical scientists on high heels.
AB  - For 250 years medical scientists have propagandized about the health hazards of
      high-heeled shoes, which originated four centuries ago. Physicians, however,
      largely unaware of their own profession's tradition, keep reinventing the
      diagnostic wheel. This professional amnesia has held back the momentum of the
      process of educating the public. Consequently, despite these warnings, millions
      of women continue to wear high-heeled shoes. This article describes the history
      of the medical profession's recognition of this worldwide health problem and the
      current understanding of the deleterious and often irreversible biomechanical
      effects of high-heeled shoewear. The article emphasizes that the reemergence of
      high heels and of medical interest in them in the third quarter of the 19th
      century, following their disappearance in the wake of the French Revolution, was
      associated with increasing pressure by employers to wear such shoes for long
      hours at work. Although medical scientists have recognized this specifically
      occupational phenomenon for more than a century, full-scale epidemiological
      studies may be necessary to bring about substantial social-behavioral change.

PMID- 9595341
TI  - The medical detection of simulated occupational injuries: a historical and social
      analysis.
AB  - Occupational malingering is often thought to involve the deliberate feigning of
      disease by workers seeking undeserved financial gain. Concern about this form of
      malingering grew in the late 19th century as a result of the emergence of the new
      industrial economy and the institution of workers' compensation insurance.
      Medical judgments about the simulation of work injuries have placed physicians in
      a crossfire between the interests of employers and workers in numerous
      medicolegal debates. Because of uncertainty about the true cause of many
      occupational disorders and the highly charged social environment in which medical
      opinions are rendered, physicians' views about malingering are often swayed by
      cultural, political, and economic forces. The historical record shows that a
      medical diagnosis of occupational malingering can reflect deep-seated cultural
      and social biases toward women, Jews, immigrants, and other groups representing a
      potential threat to the privileged social class. Current efforts to eliminate
      fraudulent workers' compensation claims must be sensitive to the inherent
      ambiguities in the medical determination of work-relatedness and the potential
      for judgments about simulated work injuries to conceal deep-seated social biases
      and class prejudices.

PMID- 9595342
TI  - Whose epidemiology, whose health?
AB  - Simplistic claims about the objectivity of science have been challenged from a
      variety of perspectives. Evaluation of the external context of production of
      knowledge and the methodological approaches to posing questions and assembling
      evidence shows that there is no pure "science"; rather, all scientific knowledge
      is shaped by the social history of its production. Examples are given of how
      quantitative concepts in modern epidemiology influence the recognition of the
      causes of disease. The author uses the phenomenon of intensive swine production
      by vertically integrated agribusiness to illustrate how broad problems such as
      environmental racism, agricultural determinants of nutrition, loss of natural
      resources, and conditions conducive to emergence of new diseases are hidden by
      epidemiological approaches that fit into corporate policy perspectives. It is
      critically important to ask who produces epidemiological knowledge, and whose
      health is promoted by that knowledge.

PMID- 9595343
TI  - Improving the appropriateness of physician prescribing.
AB  - Appropriate prescribing means that prescribers should try to maximize
      effectiveness, minimize risks and costs, and respect patients' choices. Evidence
      from studies on prescribing to individuals and from administrative databases
      reveals a significant level of inappropriate prescribing by Canadian physicians.
      Two important reasons for inappropriate prescribing seem to be physicians' level
      of knowledge and physicians' practice settings. A large number of methods have
      been tried to improve prescribing behavior, but most are unsuccessful. Academic
      detailing, and audit and feedback, have both been shown to work but may be
      difficult to implement in Canada, where most physicians practice in solo fee-for
      service settings. Alternative forms of physician payment such as capitation or
      salary are probably necessary to make prescribing more appropriate.

PMID- 9595344
TI  - Self-regulatory codes of conduct: are they effective in controlling
      pharmaceutical representatives' presentations to general medical practitioners?
AB  - Self-regulatory codes of conduct are used to control the promotional practices of
      the pharmaceutical industry, but the effectiveness of these codes in controlling
      pharmaceutical representatives' presentations has not been examined. This is a
      matter of concern because pharmaceutical representatives have more influence than
      any other promotional media on prescribing practices. The authors developed a
      method for monitoring the oral presentations of pharmaceutical representatives
      when promoting products to medical practitioners. Sixteen audio-recordings,
      detailing 64 medicines, were obtained; 38 of the 64 products were prescription
      only medicines. Information on indications and on dosage and administration was
      commonly provided, but information on other areas of drug knowledge, particularly
      product risk, was minimal. Thirteen presentations contained at least one
      inaccuracy when compared with Australian Approved Product Information.
      Presentations did not always comply with current guidelines in the Code of
      Conduct. The Code provides only limited standards for pharmaceutical
      representatives' presentations, and no active monitoring system is in place to
      ensure adherence to the code. There is an urgent need for policy development on
      the role of pharmaceutical representatives, their standards of practice, and
      regulation of their activities to ensure they contribute to the appropriate use
      of medicines.

PMID- 9595345
TI  - Globalization in the pharmaceutical industry, Part II.
AB  - This is the second of a two-part report on the pharmaceutical industry. Part II
      begins with a discussion of foreign direct investment and inter-firm networks,
      which covers international mergers, acquisitions, and minority participation;
      market shares of foreign-controlled firms; international collaboration agreements
      (with a special note on agreements in biotechnology); and licensing agreements.
      The final section of the report covers governmental policies on health and safety
      regulation, price regulation, industry and technology, trade, foreign investment,
      protection of intellectual property, and competition.

PMID- 9595346
TI  - Health and safety strategies in a changing Europe.
AB  - This article presents a synthesis of some of the more significant findings from
      two recent surveys on working conditions and national strategies for their
      improvement in the European Union in the 1990s. As patterns and organization of
      employment have changed in the past decade, the consequences for health and
      safety present new challenges for legislators, the social partners, the
      regulatory agencies, and the specialists. These challenges are only partially met
      in most European member states. Because of the continued deregulation of
      employment, reduced public expenditure, and reduced trade union presence, the
      operation of strategies to implement a common framework of E.U. legislation is
      limited and often incomplete. This issue must be confronted if systems for
      promoting the well-being of people at work in Europe are to keep up with the
      rapidly changing nature of the risks that they face.

PMID- 9595347
TI  - From the North Sea to the Mediterranean? Constraints to health reform in Greece.
AB  - The report of an international experts' committee, recently invited by the
      Ministry of Health to review Greece's health care system, recommended the
      creation of a network of family doctors, reimbursed on a capitation basis. The
      committee also proposed that family doctors should manage a budget for the
      purchase, on behalf of their patients, of specialist and hospital services and
      drugs. The author examines the exportability of the fundholding experience from
      Britain to a country in which health care organization is very different, social
      health insurance is fragmented, private health care is large and growing,
      ambulatory health care services are provided by specialists, and behavioral
      cultural factors cast doubt on the consequences of the proposed change. An
      attempt to implement fundholding in Greece is likely to have effects opposite to
      those intended. The more humble task of tackling the inequities and
      inefficiencies of the present system should be the starting point of all future
      reform projects.

PMID- 9595348
TI  - Race, class, and violence: research and policy implications.
AB  - A public health approach to preventing interpersonal violence involving
      perpetrators and victims is laudable, but fraught with social and political
      pitfalls. The concept of "race" is little understood and is being exploited by
      both academics and the media, putting racial minorities--particularly blacks, who
      tend to be overrepresented in data on reported violence--at further risk. Though
      race is acknowledged as an ambiguous concept, some dangers nonetheless persist in
      linking racial minorities to dysfunctional and antisocial behavior within both
      cultural and biological constructs. Recommendations are given to help ameliorate
      the effects of such contextual linking, particularly given the present mood of
      U.S. political conservatism.

PMID- 9595349
TI  - Psychiatric hospitals and instrumental rationality.
AB  - Therapists in psychiatric hospitals often overuse a model borrowed from natural
      science, with the patient becoming an object to be examined, assessed, and
      altered, and underuse an interpretive psychotherapeutic approach, or misuse it to
      control patients. And while expressing an interest in the meaning of what
      patients say, they exclude most of the traditional sources of meaning, in ethics,
      religion, literature, art, and political thought. The author argues that
      therapists do these things for two ideological reasons: to maintain their
      position in the authoritarian structure of the hospital and to maintain the
      hospital as an agent of class domination. Along with other groups, therapists
      bring instrumental rationality, such as that of natural science, to bear on
      political, cultural, and personal questions for which this type of rationality is
      often destructive. In the long run, political participation and social
      integration decrease, culture traditions provide less meaning, and personality
      formation is disrupted. Thus the end result of the overuse of instrumental
      rationality is not only domination by one class of others, but a decrease in the
      stability of the society as a whole. Hospital therapists participate in these
      trends, but they could do otherwise, by working to create a more democratic form
      of therapy.

PMID- 9595350
TI  - Oral rehydration for diarrhoea: symptomatic treatment or fundamental therapy.

PMID- 9595351
TI  - Systemic atherosclerosis in dogs: histopathological and immunohistochemical
      studies of atherosclerotic lesions.
AB  - Histopathological and immunohistochemical studies were carried out on five cases
      of canine systemic atherosclerosis. The five animals were male, and showed
      hypercholesterolaemia and hypertriglyceridaemia on biochemical analysis of
      plasma. Histopathologically, atherosclerotic lesions were seen in the aorta and
      muscular arteries in many organs, including the heart, spleen, kidneys, lungs,
      pancreas, alimentary tract, urogenital organs, eyes, prostate and urinary
      bladder. The lesions were characterized by the deposition of lipids and
      infiltration of lipid-laden foamy cells in the tunica intima and tunica media,
      sometimes forming fibrofatty plaques, containing abundant sudanophilic material,
      cholesterol clefts and mineralized material. The lesions started in the tunica
      intima and extended to the tunica media and tunica adventitia.
      Immunohistochemical examination with canine apolipoprotein B-100 (CApoB-100)
      antibody identified the lipids containing low density lipoprotein.
      Immunoreactivity to CApoB-100 antibody was recognized in the tunica intima, lipid
      laden foamy cell cytoplasm and smooth muscle cells in the tunica media, and
      fibrofatty plaque. These histopathological and immunohistochemical features were
      similar to those of human atherosclerotic lesions.

PMID- 9595352
TI  - Immunohistochemical characterization of hepatic lesions associated with
      Elaeophora elaphi parasitism in red deer (Cervus elaphus).
AB  - This study was based on the immunohistochemical characterization of hepatic
      lesions caused by Elaeophora elaphi in 15 red deer. In eight animals filariae
      were found in branches of the portal vein. "Web-like" endophlebitis (15 cases),
      lymph nodule-like thrombi associated with filarial debris (12 cases) and
      fibrinous thrombi (three cases) were also observed in the portal vein. Multifocal
      granulomatous hepatitis (six cases) and lymph nodule-like tissue (three cases)
      were found in the liver parenchyma. The distribution of CD3 antigen, IgG-lambda
      light chains, and S-100 protein in lymphoid tissue in the portal vein thrombi and
      hepatic parenchyma was similar to that found in the cortex of the lymph nodes. In
      these lesions, lymphoid follicles with large germinal centres (mainly composed of
      IgG+ B lymphocytes, with occasional S-100+ follicular dendritic cells)
      predominated over interfollicular lymphoid tissue (mainly composed of CD3+ T
      lymphocytes and S-100+ interdigitating cells). This suggested that the local
      humoral immune response was more important than the cellular response in this
      parasitic disease. The presence of interdigitating and follicular dendritic cells
      confirmed the high degree of organization of the abnormal lymphoid tissue and
      suggested that antigen presentation to T and B lymphocytes and the subsequent
      proliferation of the latter was particularly efficient in such tissue. The latter
      may therefore be superior to diffuse granulomatous infiltrate in terms of the
      production of a local immune response.

PMID- 9595353
TI  - Functional and structural characterization of isolated perfused stingray liver
      including effects of ischaemia/reperfusion.
AB  - The morphological and functional characteristics of stingray liver were studied,
      including the effect of ischaemia/reperfusion. With an isolated perfused model,
      it was shown that the stingray liver was more resistant than the rat liver to
      ischaemia/reperfusion injury; this was consistent with the differing partial
      oxygen tensions usually present in the two species. This study confirmed that
      whereas stingray hepatocytes form tubules with central bile canaliculi as in
      other fish, the stingray liver has portal triads and a lobular architecture as in
      mammals. Apoptosis of hepatocytes, demonstrated in the normal liver, was only
      marginally enhanced by ischaemia/reperfusion. Resulting apoptotic bodies were
      phagocytized by macrophage-like cells in hepatocyte tubules. In contrast to rat
      liver, the stingray liver showed no necrosis after ischaemia-reperfusion.

PMID- 9595354
TI  - Ultrastructural study of porcine alveolar macrophages infected in vitro with
      porcine reproductive and respiratory syndrome (PRRS) virus, with and without
      Haemophilus parasuis.
AB  - Two experiments were designed to study ultrastructural changes in porcine
      alveolar macrophages (PAM) inoculated with porcine reproductive and respiratory
      syndrome (PRRS) virus (experiment 1) and with PRRS virus and Haemophilus parasuis
      (experiment 2). In both experiments, the viral infectious dose represented a
      "multiplicity of infection" of 1. Viral infection alone induced minimal
      ultrastructural changes at this dose, consisting only of an increase in lysosome
      numbers. Mixed viral and bacterial infection induced the production of greatly
      increased numbers of phagosomes and phagolysosomes. The PAM were of low efficacy
      in phagocytizing H. parasuis. PRRS virus infection had only a minimal effect on
      the phagocytosis of H. parasuis by PAM. It is suggested that the virus induces
      PAM activation rather than PAM destruction.

PMID- 9595355
TI  - Particle clearance from the gills of rainbow trout (Oncorhynchus mykiss).
AB  - The rate of particle clearance from the gills was assessed in healthy rainbow
      trout (Oncorhynchus mykiss), challenged with the formalin-killed bacterium
      Flavobacterium branchiophilum, as well as in fish with altered ventilation levels
      produced by varying the concentrations of dissolved oxygen (DO) in the water. The
      clearance of F. branchiophilum from the gills was quantified by means of an
      enzyme-linked immunosorbent assay. Fish held under normoxic conditions (DO = 9.5
      mg/l) showed an initial rapid reduction in bacterial antigen, with 50% of the
      bacteria being cleared in the first 12 h after exposure, followed by slower
      clearance for the remaining bacteria; total elimination was achieved by 40 h.
      Fish with reduced ventilation rates (hyperoxia; DO = 25 mg/l) and elevated
      ventilation rates (hypoxia; DO = 4.5 mg/l) had significantly impaired particle
      clearance (r < 0.05), achieving only 60 and 20% reduction, respectively, at 72 h
      after challenge.

PMID- 9595356
TI  - Odontometric microevolution in the Valley of Oaxaca, Mexico.
AB  - Tooth crown lengths, breadths, and areas were compared from five sequential human
      skeletal samples from the Valley of Oaxaca, Mexico, spanning the period from 1600
      BC to AD 1521. Almost all of the measurements considered exhibited dramatic
      reduction over that period. Total crown area declined from 1320 mm2 to 1262 mm2,
      a change of 4.4% or 9.4 darwins, which is noticeably larger than any previously
      reported rate of dental reduction in a recent human population. This reduction
      was greatest in posterior tooth breadths, especially in the mandible. The
      patterning of the reduction, and of the variance of the measurements, indicates
      that natural selection was primarily responsible for the change. Of all the
      measurements, anterior breadths appear to have been the least subject to
      selection, and posterior lengths the next least. The degree of reduction suggests
      that selective pressures towards smaller teeth were greater in Mesoamerica than
      elsewhere. This case provides an example of the value of recent human skeletal
      series for the study of microevolutionary processes.

PMID- 9595357
TI  - Structural design of the femoral neck in primates.
AB  - This study investigates the structural design of the femoral neck with respect to
      phylogeny, locomotor behavior, and body size in a large comparative sample of
      primates. Since a bone's strength is determined by the amount and arrangement of
      its constituent material, the amount and distribution of bone in the femoral neck
      are the focus of the present study. Two types of data were collected. First, the
      total distribution of bone across the femoral neck (perpendicular to the femoral
      neck axis) was examined using image analysis techniques. The distribution of both
      cortical and trabecular bone are included in this analysis. Secondly, the
      external dimensions of the femoral neck and the thickness of the superior and
      inferior cortices, measured from radiographs, were used to calculate femoral neck
      cross-sectional properties (cortical area and second moment of area). These data
      were input into a simplified cantilevered beam model that incorporates femoral
      neck-shaft angle and femoral neck length and is used to predict stress under one
      unit body mass of loading on the femoral head. The patterns of bone distribution
      in the femoral neck between taxa are broadly similar for the analysis that
      includes both trabecular and cortical bone and that which includes only cortical
      bone. In all cases, there tends to be more bone on the inferior aspect of the
      femoral neck compared to the superior aspect. However, the non-human hominoids
      and New World monkeys (e.g., Ateles and Alouatta) have a more even distribution
      of bone across the femoral neck and have thicker superior cortices relative to
      inferior cortices compared to the rest of the comparative sample, including
      humans. It is proposed that the more equal distributional pattern in the non
      human hominoids and atelines reflects less stereotypical, more generalized
      loading orientations. Differences between species in overall strength of the
      femoral neck are a function of both body size and locomotor mode.

PMID- 9595358
TI  - Myological correlates of prosimian leaping.
AB  - Although the skeletal correlates of vertical clinging and leaping behavior in
      primates have been studied in great detail, myological information on this
      locomotor group is not readily available. We here provide relative muscle mass
      data for the hindlimb of four prosimian leapers, representing indriids as well as
      the small-bodied tarsiers and galagos. Wet weights of all hindlimb muscles, with
      the exception of the intrinsic muscles of the foot, were determined. For
      comparative purposes muscle weights were also gathered for Varecia, an arboreal
      quadruped, and previously unpublished dry muscle weights of several monkeys are
      included as well. The specialized leapers are characterized by a predominance of
      muscles for hindlimb joint extensions. Indriids have larger hip extensors than
      ankle plantarflexors, whereas the galago and tarsier display the reverse
      condition. This dichotomy in relative muscle mass corresponds to a dichotomy in
      leaping kinematics, with indriids going through a greater range of movement at
      the hip joint and galagos and tarsiers at the ankle joint. However, the most
      striking result is the overwhelming dominance of the quadriceps femoris muscle in
      both groups. This suggests that power may be transferred from the knee and thigh
      to adjacent joints and segments. In contrast, quadrupedal primates have more
      extensor musculature at the hip, suggesting that the need for a short swing phase
      pendulum constrains muscle mass distribution within the limb of quadrupeds. Total
      muscle mass of the hindlimb as well as the mass of the propulsive muscles scale
      with body mass at exponents below the functional equivalence expectation. Larger
      bodied leapers therefore have less muscle force available per unit body weight to
      be propelled than their smaller-bodied counterparts.

PMID- 9595359
TI  - Estimation of African ape body length from femur length.
AB  - The estimation from long bone lengths of stature in humans or body size in apes
      has a deep history in physical anthropology. To date, we can enumerate at least
      five different statistical methods for making such estimations. These methods
      are: (1) the regression of body length on long bone length (inverse calibration),
      (2) regression of long bone length on body length followed by solving for body
      length (classical calibration), (3) major axis regression of body length on long
      bone length, (4) reduced major axis regression of body length on long bone
      length, and (5) use of a long bone/body length ratio. We examine some of the
      statistical properties of these estimators using a large sample of humans (n =
      2053) to derive the estimators, and applying them to smaller samples of Pan
      troglodytes (n = 42), Pan paniscus (n = 8), and Gorilla gorilla (n = 35). Based
      on the root mean-squared error (RMSE), the reduced major axis is the preferred
      estimator for body length in the combined Pan sample. However, inverse
      calibration is the best estimator for body length in gorillas based on the RMSE.
      Many estimators grossly underestimate body length in the apes. Differences in
      allometries between humans and great apes are obvious, but it is important to
      show the assumptions necessary in estimating body size from fossil remains,
      especially when isolated long bones are recovered and the global allometry is
      consequently unknown.

PMID- 9595360
TI  - Long-term technical evolution and human remains in the Anatolian palaeolithic.

PMID- 9595361
TI  - Left ventricular hemodynamics in anemic fetal lambs.
AB  - OBJECTIVE: To assess the left ventricular determinants of cardiac output in 12
      chronically instrumented fetal lambs, six of which where made anemic. METHODS:
      Twelve, singleton pregnant ewes were instrumented between 123-126 days gestation
      and chronic catheters placed in-situ. In six fetal lambs, isovolemic fetal anemia
      was induced (reducing the hematocrit from a mean of 35% to 20%). In a prospective
      study, absolute 'beat-to-beat' LV volumes and pressures were obtained
      (gestational age 131-134 days) using a conductance catheter method and a
      comparison made with non-anemic fetal lambs. RESULTS: The group of anemic fetuses
      (n = 6) had a significantly reduced hematocrit as compared to the control group
      (37% decrease: mean difference--13.4%; P < 0.001). The arterial blood gases of
      the two groups were not statistically different, with the exception of the pO2
      and oxygen content which were significantly lower in the anemic group (P < 0.05).
      There was no significant change in fetal heart rate, LV preload (as assessed by
      venous pressure, end-diastolic volume and pressure) or mean arterial pressure
      between the anemic and control groups. However, a 75% increase in LV stroke
      volume was observed in the anemic fetal lambs (P < 0.05), secondary to a 61% fall
      in LV afterload (P < 0.05). There was no significant change in inherent
      myocardial contractility of the LV, although this did increase to approach
      statistical significance in the anemic group (P = 0.056). The diastolic time
      interval was increased by 22% in the anemic fetus, possibly allowing prolonged LV
      filling time. The indices measuring LV relaxation (Tau and dP/dtmin) were not
      significantly different in either group. CONCLUSIONS: This is the first study to
      report absolute left ventricular volumes in the anemic ovine fetus and the
      relationship of these data to LV pressure during the cardiac cycle. The model
      used produces a state of moderately severe, non-hydropic, isovolemic, fetal
      anemia consistent with those previously described. Although the anemic state was
      not prolonged, an observed increase in LV stroke volume (which is predominantly
      due to a decrease in afterload) has been described.

PMID- 9595362
TI  - The incidence of retinopathy of prematurity and steroid therapy for broncho
      pulmonary dysplasia.
AB  - To determine whether prolonged dexamethasone therapy, used in the treatment of
      bronchopulmonary dysplasia (BPD), affects the incidence of retinopathy of
      prematurity (ROP), premature born infants (Gestational age < 33 weeks) treated or
      not with dexamethasone for BPD were retrospectively studied over a 5 year period.
      Although the dexamethasone treated group had a significant lower gestational age
      and a longer period of total ventilatory support there was no significant
      difference in incidence of ROP between the groups.

PMID- 9595363
TI  - TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis
      and premature labor.
AB  - Inflammatory cytokines seem to play a key role in mechanisms initiating labor.
      Since cytokine levels are higher in preterm than in term labor, it has been
      hypothesized that labor-inducing effects of cytokines are inhibited by an
      upregulated production of cytokine antagonists, such as soluble cytokine
      receptors, at early stages of gestation. In this study, TNF, IL-1, IL-6, IL-8 and
      soluble TNF receptors (sTNFRs) were measured in amniotic fluid samples from a) 39
      women in premature labor, b) 25 women who where not in labor but delivered
      prematurely, and c) 33 women in term labor. Fifty-four of the placentas from
      premature deliveries were evaluated for presence of histological
      chorioamnionitis. Chorioamnionitis was associated with increased levels of TNF,
      IL-1 and IL-6, whereas elevated IL-1, IL-6 and IL-8 concentrations were found in
      premature parturition with no signs of infection. Concentrations of sTNFR were
      lower in preterm than in term deliveries. The present study confirms the
      participation of inflammatory cytokines in parturition. Multivariate analysis
      suggests a dominant, role of IL-1 in the presence of chorioamnionitis, whereas IL
      6 seems to be more important during idiopathic premature labor. TNFR data do not
      support the hypothesis that production of cytokine antagonists is upregulated
      prematurely to prevent partirution.

PMID- 9595364
TI  - Hyperinsulinism, neonatal obesity and placental immaturity in infants born to
      women with one abnormal glucose tolerance test value.
AB  - Several groups have reported a risk of fetal macrosomia in pregnancies with
      maternal glucose intolerance which is intermediate between gestational diabetes
      (GDM) and normal glucose tolerance. The present study was designed to determine
      whether these pregnancies are also at risk for fetal obesity, hyperinsulinism and
      placental villous immaturity. 325 women with risk factors for GDM underwent a 75
      g OGTT interpreted according to the O'Sullivan criteria. All women who met the
      criteria for GDM were managed with diet therapy. Insulin therapy was added for
      women with a mean serum glucose value > 100 mg/dl on a 24 hour glucose profile.
      Patients not meeting the GDM criteria were managed without special intervention.
      Primary outcome variables were measures of neonatal weight and skinfold
      thickness, fetal and neonatal insulin and glucose concentration, and placental
      villous maturation. Outcome parameters were compared among three groups:
      pregnancies with normal OGTT (control, n = 95), 1 abnormal value in the OGTT (1
      abnl, n = 76) and GDM (n = 154). The outcome of pregnancies with 1 abnormal value
      in the OGTT was different from those with normal OGTT. Regarding fetal growth,
      rates of LGA were approximately twice as high in groups with one abnormal value
      and GDM (21% and 24%) compared to women with normal OGTTs (11%: p < 0.05 vs GDM
      and p = 0.07 vs 1 abnormal value). The percent of infants with skinfold thickness
      > 90th percentile was also greater in the 1 abnormal value and GDM groups (31.1
      and 31.6% respectively) compared to controls (19.2%; p < 0.05 for GDM vs control
      only). Regarding fetal hyperinsulinism, AFI concentrations were similar in
      control and GDM groups (3.1 +/- 0.4 and 3.4 +/- 0.8 microU/ml, respectively), but
      were higher in the group with one abnormal OGTT value (4.3 +/- 1.2 microU/ml, p <
      0.05 vs controls). Cord blood insulin: glucose ratios were elevated in both the 1
      abnormal value and GDM groups (0.22 +/- 0.05 and 0.20 +/- 0.02 microU/ml per
      mg/dl), compared to controls (0.12 +/- 0.01 microU/ml per mg/dl, p < 0.05 vs 1
      abnormal value). Neonatal glycemia < 30 mg/dl was significantly more common in
      the one abnormal value than in the control group (49% vs 34% of infants) and
      intermediate in the GDM group (40%). Severe placental villous immaturity was more
      than twice as frequent in the 1 abnormal value group compared to controls (24% vs
      9%, p < 0.05) and the most frequent in the GDM group (33%; p < 0.001 vs
      controls). Pregnancies with glucose intolerance below the thresholds for
      diagnosis of GDM have an increased risk for fetal obesity, hyperinsulinism,
      postpartum hypoglycemia and placental immaturity. These findings indicate the
      continuum of risk for fetal morbidity associated with increasing maternal glucose
      intolerance in pregnancy.

PMID- 9595365
TI  - Respiratory tract colonization with mycoplasma species increases the severity of
      bronchopulmonary dysplasia.
AB  - There is controversy regarding the role of mycoplasmas (MP) colonizing the
      neonatal respiratory tract in the development of bronchopulmonary dysplasia
      (BPD). To determine the association of respiratory MP colonization and BPD.
      Retrospective analysis of neonates (26-32 weeks of gestation) intubated for
      respiratory insufficiency. Tracheal aspirate cultures were obtained for MP if the
      lung disease was not improving by 7-10 days or there were radiographic changes
      suggestive of inflammation. Of 63 infants who had tracheal aspirates sent, 17 had
      positive MP cultures. We found no significant difference in the gestational ages
      (27.6 +/- 0.4 vs 27.8 +/- 0.2 weeks) or birth weights (1097 +/- 86 vs 997 +/- 42
      grams) in MP positive vs negative infants. No differences were noted in antenatal
      or postnatal steroid use, gender, race, sepsis, RDS, PDA, air leaks, NEC, GER,
      days on positive pressure ventilation or days on oxygen. There were significantly
      (p = 0.04) more infants with severe BPD (defined as oxygen requirement at 36
      weeks corrected post menstrual age) among MP positive (n = 14; 82%) versus MP
      negative (n = 25; 54%) infants. Presence of MP in the tracheal aspirates is
      associated with an increased likelihood of developing severe BPD.

PMID- 9595366
TI  - Low degree of regionalization and high transfusion rates in very low birthweight
      infants: a survey in Germany.
AB  - Although anemia is common in very low birthweight (VLBW) infants, widely accepted
      guidelines for red blood cell transfusions are lacking. Questionnaires regarding
      transfusion policy in VLBW infants in 1994 were sent to 391 German pediatric
      departments. 208 questionnaires were returned. 51 departments reported not to
      admit VLBW infants. Thus, results are based on 157 completed questionnaires. 54%
      of the respondents admitted less than 30 VLBW infants per year and 52% of the
      VLBW infants were admitted to departments with less than 50 VLBW infants per
      year. Overall transfusion rate ranged from 0 to 100% (median 65%). This range
      narrowed with the departments' size indicating stricter guidelines with less
      variation. Indication for transfusion varied considerably depending on the
      infants' postnatal age and need for ventilatory support. 34% of the respondents
      applied directed transfusions, most frequently from the infant's father. 70% used
      satellite packs. 51% stored the packs up to 7 days, 10% longer than 14 days. Red
      cells were irradiated in 35%, and washed in 23% of the departments. Median single
      transfusion volume was 12 ml/kg. We conclude that regionalization of VLBW infants
      in Germany is far from completeness and that hospital policies for transfusion
      show large variety especially in small departments.

PMID- 9595367
TI  - Relationship between MLR blocking antibodies and the outcome of the third
      pregnancy in patients with two consecutive spontaneous abortions.
AB  - To determine the relationship between mixed lymphocyte culture reaction (MLR)
      blocking antibodies (BAbs), immunological humoral factors, which generated in
      pregnant women and the outcome of pregnancy, the natural outcome of the third
      pregnancy in fifty-five patients with primary twice consecutive abortion was
      evaluated, and MLR-BAbs in sera were examined during their third pregnancy. The
      third pregnancy in 39 of 55 patients (70.9%) continued successfully, and
      remaining 16 patients (29.1%) experienced repeated abortion at the first
      trimester. Out of these 55 patients, MLR-BAbs were examined in 27 (17 with
      successful outcome and 10 with repeated abortion). The positive rate of MLR-BAbs
      was 82.4% in patients with successful outcome (15 of 17 cases), and that in
      patients with repeated abortion was 10% (one of 10 cases). The positive rate of
      MLR-BAbs was significantly higher in the successful pregnancy group compared with
      that in the repeated abortion group (p < 0.001). The blocking effect on MLR
      significantly increased along with the prenatal course in patients with
      successful outcome. Thus, MLR-BAbs are strongly associated with the outcome of
      pregnancy in patients with primary twice consecutive spontaneous abortions.

PMID- 9595368
TI  - Umbilical arterial flow change during hemodialysis.
AB  - A pregnant woman was performed hemodialysis 3 times a week from early gestation.
      At 30 weeks of gestation, fetal growth and amniotic fluid volume were normal. We
      performed 3-hour hemodialysis 6 times a week. Cesarean section was performed at
      38 weeks of gestation, she delivered a healthy neonate weighing 2575 g. During
      hemodialysis, we performed Doppler flow velocimetry on the umbilical artery. The
      resistance index revealed a remarkable decrease after 1.5 hour hemodialysis. But
      it recovered 3 hours of administration as well as after completion of treatment.
      We speculated this change in the resistance index of the umbilical artery was
      caused by transient maternal hypovolemia.

PMID- 9595369
TI  - Detection of C-type natriuretic peptide in normal pregnancy.
AB  - C-type natriuretic peptide (CNP) is a recently identified member of the family of
      natriuretic peptides that plays an important role in the regulation of blood
      pressure, renal function and volume homeostasis. Its effects are mainly
      hypotensive and natriuretic. CNP is also considered to be an autocrine/paracrine
      regulator of the endothelium as well as a neuropeptide. Little is known about its
      role as a circulating substance. There are only few data of CNP plasma levels and
      changes in disease. Using a highly specific radioimmunoassay we established for
      the first time CNP plasma levels of normal pregnancies 5.9 +/- 1.5-8.6 +/- 2.1
      pg/ml) and a non-pregnant control group (8.1 +/- 1.7 pg/ml). In contrast to
      atrial natriuretic peptide and brain natriuretic peptide we have not found
      significant differences of the plasma levels during normal pregnancy and no
      difference to the non-pregnant control group.

PMID- 9595370
TI  - Prenatal diagnosis of fetal urogenital abnormalities with oligohydramnios by
      magnetic resonance imaging using turbo spin echo technique.
AB  - Turbo spin echo technique is a sequence that enables T2 weighted magnetic
      resonance (MR) images to be obtained in a few seconds. The purpose of this study
      is to evaluate the usefulness of this sequence in the prenatal diagnosis of fetal
      urogenital abnormalities associated with oligohydramnios, which make the
      ultrasound examination inconclusive. Two fetuses suspected of having prune belly
      syndrome and polycystic kidney on ultrasound examination were studied by MR
      imaging using turbo-spin echo method in utero. The images were compared with
      prenatal ultrasonography or post-mortem findings. In both fetuses, abnormalities
      were diagnosed correctly. This sequence is useful because it provides images of
      diagnostic quality in a very short scanning time.

PMID- 9595371
TI  - Need to change our way of thinking on birth time.

PMID- 9595372
TI  - Calcium channel blockers in veterinary medicine.
AB  - Calcium channel blockers are becoming increasingly popular in veterinary medicine
      for the treatment of systemic hypertension, cardiac arrhythmias, and hypertrophic
      cardiomyopathy. Calcium is vital to many cellular functions and thus stringent
      regulation of intracellular calcium concentrations is required. Pharmacologic
      manipulation of the regulatory mechanisms has the potential to alter cellular
      function in all body systems. In human medicine, calcium channel blockers are
      being evaluated for, among other things, use in treating glaucoma, deep vein
      thrombosis, and pulmonary hypertension, in renal transplantation, and for
      prevention of reperfusion injury. The potentially beneficial effects of these
      drugs have often been overshadowed by adverse effects including hypotension,
      inappetence, bradycardia, conduction abnormalities, and decreased cardiac output.
      With the introduction of sustained-release formulations (diltiazem) and 2nd
      generation calcium channel blockers (amlodipine) many of these effects have been
      attenuated or eliminated. This paper will review the functions of calcium and the
      calcium channels as well as discussing the classes and current and potential uses
      of the various calcium channel blockers.

PMID- 9595373
TI  - Relation between habitual diet and canine mammary tumors in a case-control study.
AB  - In the present case-control study several dietary and nutritional factors were
      investigated to determine if a relationship exists between diet and development
      of mammary tumors in female dogs. Control female dogs (n = 86) were compared with
      a case group of dogs (n = 102) with dysplasias or tumors of the mammary gland. A
      questionnaire providing information on the dog's body conformation and dietary
      and reproductive histories was answered by the owners. Serum selenium and retinol
      concentrations and the fatty acid profile in subcutaneous adipose tissue were
      analyzed as indicators of nutritional status. Obesity at 1 year of age and 1 year
      before the diagnosis of mammary nodules was found to be significantly related to
      a higher prevalence of mammary tumors and dysplasias. The intake of homemade
      meals (compared to that of commercial foods) was also significantly related to a
      higher incidence of tumors and dysplasias. Other significant risk factors were a
      high intake of red meat, especially beef and pork, and a low intake of chicken.
      The subcutaneous fatty acid profile and the serum selenium concentration were not
      significantly different in the cases and the controls, with the exception of
      C18:1 fatty acid (oleic acid) content, which was significantly higher in the
      cases than in healthy controls. Serum retinol concentration was significantly
      lower in the cases than in the controls. In the multivariate analysis, older age,
      obesity at 1 year of age, and a high red meat intake were independently and
      significantly associated with the risk of developing mammary tumor and
      dysplasias.

PMID- 9595374
TI  - Factors associated with survival in septicemic foals: 65 cases (1988-1995).
AB  - In order to identify variables obtained at admission that could be used to
      predict survival in septicemic foals, medical records of 65 foals diagnosed with
      septicemia were reviewed. Initially, variables were analyzed independently
      (univariate analysis) for association with survival. Of the physical examination
      and historical data examined using univariate analysis, the ability to stand at
      admission, respiratory rate > or = 60 breaths per minute (bpm), and normal
      appearing mucous membranes were significantly associated with survival. Foals
      with history of induced parturition were significantly less likely to survive.
      The following hematologic and serum biochemical variables determined at admission
      were significantly associated with survival: white blood cell count > or = 6,000
      cells/microL, neutrophil count > 4,000 cells/microL, serum albumin concentration
      > 2.2 g/dL, serum glucose concentration > 120 mg/dL, blood pH > or = 7.35, and
      positive base excess. The administration of plasma at admission was significantly
      associated with survival. Stepwise multiple logistic regression analysis was
      performed to evaluate the association between survival and variables identified
      as significantly associated with survival in bivariate analysis. The final
      multivariate model selected included the variables standing, duration of clinical
      signs (24-hour intervals) prior to admission, respiratory rate > or = 60 bpm,
      neutropenia (< or = 4,000 cells/ microL), and neonatal age category. The
      probability of survival was significantly increased for foals that were standing,
      had a respiratory rate > or = 60 bpm, and that had a neutrophil count > 4,000
      cells/microL at admission. Probability of survival was significantly decreased
      for foals that had a longer duration of clinical signs prior to admission. For
      each 24 hours of duration, the estimated risk of death was increased by 5.8-fold.

PMID- 9595375
TI  - A syndrome resembling idiopathic noncirrhotic portal hypertension in 4 young
      Doberman pinschers.
AB  - We describe 4 young male Doberman Pinschers (3 littermates and 1 unrelated dog)
      with a syndrome resembling idiopathic or noncirrhotic portal hypertension of
      humans. Each dog was evaluated for a hepatopathy resulting in portal
      hypertension, development of portosystemic collateral vessels, and hepatic
      encephalopathy. These dogs differ from previous reports of young dogs with
      hepatic insufficiency associated with portal hypertension and acquired portal
      systemic shunting by their lack of intrahepatic arteriovenous fistulae, portal
      vein atresia, or intrahepatic fibrosis. Clinicopathologic features included
      erythrocyte microcytosis, normal to mildly increased liver enzyme activities,
      increased concentrations of serum bile acids, reduced plasma indocyanine green
      clearance, and normal total bilirubin concentration. Abdominal ultrasonography
      disclosed a small liver and portosystemic collateral vessels. Radiographic
      imaging studies confirmed hepatofugal portal circulation and discounted hepatic
      arteriovenous fistulae. Histopathologic features in liver tissue from each dog
      were similar and consistent in all sections examined. Common findings included
      increased cross-sectional views of hepatic arterioles; hepatic lobular atrophy;
      scanty increase in connective tissue around some large portal triads; and absence
      of inflammation, disturbed lobular architecture, bile duct proliferation, or
      intrahepatic cholestasis.

PMID- 9595376
TI  - Amlodipine: a randomized, blinded clinical trial in 9 cats with systemic
      hypertension.
AB  - The efficacy of amlodipine (AML) was tested in hypertensive cats in a placebo
      controlled, randomized, blinded clinical trial. Five cats were randomized to
      receive 0.625 mg AML once daily and 4 cats to receive placebo (PLA) once daily.
      The average systolic blood pressure (SBP) recorded by the Doppler method on day 0
      was 212 +/- 21 mm Hg in the AML group and 216 +/- 32 mm Hg in the PLA group. On
      day 7, the cats receiving AML had a significantly lower average daily SBP (160 +/
      30 mm Hg) but SBP in the PLA group was unchanged (207 +/- 31 mm Hg). On day 7,
      all cats receiving PLA and one cat receiving AML were crossed over to the other
      group because of inadequate response. Blood pressure did not decrease adequately
      in 3 cats by day 14 (7 days of PLA and 7 days AML) and the treatment code was
      broken. Each of these cats was subsequently administered 1.25 mg AML daily. Cats
      requiring 1.25 mg AML once daily (6.1 kg +/- 0.7 kg) weighed significantly more
      than cats that responded to 0.625 mg AML once daily (4.1 +/- 0.7 kg). The average
      daily SBP recorded in the 6 cats that completed the study was significantly lower
      after 16 weeks of treatment (152 +/- 14 mm Hg) compared to day 0 (221 +/- 24 mm
      Hg). Three cats were euthanized before completion of the study. All 3 cats were
      responders to AML on day 7. SBPs measured 24 hours after AML administration were
      similar to the average daily SBP, suggesting that AML effectively controlled SBP
      for a 24-hour period. AML was shown to be an effective once-daily
      antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03
      mg/kg sid.

PMID- 9595378
TI  - Acute reactions in dogs treated with doxorubicin: increased frequency with the
      use of a generic formulation.
AB  - During a 4-month period, 34 dogs with tumors received a total of 60 doses of a
      single generic formulation of doxorubicin; 13 acute drug reactions were observed
      in these 34 dogs, and no acute reactions were observed after replacing the
      product with the proprietary brand. These reactions were characterized by one or
      more of the following signs: pruritus; head-shaking; urticaria; erythema of the
      pinnal, axillary, or inguinal regions; vocalization; vomiting; hyperemic or pale
      mucous membranes; high heart rate; and high respiratory rate. We propose that a
      component unique to generic doxorubicin was responsible for the unusually high
      number of acute drug reactions observed.

PMID- 9595377
TI  - Pulmonary eosinophilia associated with increased airway responsiveness in young
      racing horses.
AB  - Horses are known to acquire small airway disease (SAD), an allergen-induced
      naturally occurring syndrome of reversible obstructive lung disease accompanied
      by airway hyperresponsiveness and increased inflammatory cell numbers on
      bronchoalveolar lavage (BAL). This disorder has received scant attention in young
      racehorses. The purpose of the present report was to examine the effect of BAL
      eosinophilia in young racehorses on clinical examination, BAL, hematology, airway
      responsiveness, and on pulmonary function at rest and after a standardized
      exercise challenge. Five (3 males, 2 females; age 2.6 +/- 0.9 years) with a
      history of respiratory compromise and BAL eosinophil differential count > 5% and
      6 controls (4 males, 2 females; age 3.5 +/- 1.0 years) training and performing to
      expectation with normal BAL cell differential (eosinophils < 1%) were studied.
      Respiratory system clinical examination was performed and expressed as a clinical
      score. Arterial blood gas measurements, CBC, and pulmonary function testing were
      performed at rest. Pulmonary mechanics measurements were repeated 1 hour and 20
      hours after a standardized treadmill exercise challenge. Incremental histamine
      inhalation challenge was performed and the concentration of histamine effecting a
      35% decrease in dynamic compliance (PC35CDyn) was determined. Significant
      differences were noted between and controls with regard to clinical score (P =
      .01), blood eosinophils (P = .04), BAL cell count (P = .04), BAL macrophage
      differential (P = .04), PC35CDyn (P = .008), and tidal volume and respiratory
      rate at 20 hours following exercise challenge (P = .05). We conclude that
      pulmonary eosinophilia and airway hyperresponsiveness are manifest in some young
      horses without overt airway obstruction at rest. We speculate that these may be
      early events in the natural progression of heaves.

PMID- 9595379
TI  - Electrolyte disturbances in foals with severe rhabdomyolysis.
AB  - Marked electrolyte abnormalities characterized by profound hyperkalemia,
      hyponatremia, hypocalcemia, and hyperphosphatemia were noted in 4 neonatal foals
      with acute rhabdomyolysis and pigmenturia. In 2 foals, rhabdomyolysis developed 4
      6 days after admission for dysmaturity, and in 2 foals, rhabdomyolysis was
      evident on presentation. Rhabdomyolysis was a consequence of selenium deficiency
      with or without vitamin E deficiency, possibly combined with increased oxidant
      stress due to sepsis or hypoxia and reperfusion injury after parturition. Foals
      gained from 7 to 15% of their initial body weight within 48 hours of developing
      rhabdomyolysis. Three of the foals developed cardiac arrhythmias characterized by
      spiked T waves and decreased-amplitude P waves. Postmortem examination of 2 foals
      revealed extensive myodegeneration and renal tubular nephrosis; renal cortical
      necrosis with myocardial necrosis was noted in 1 foal. Destruction of the major
      intracellular compartment (intracellular fluid [ICF]) through extensive
      myonecrosis combined, in some cases, with myoglobinuric renal insufficiency
      produced major fluid shifts and life-threatening electrolyte derangements. With
      the major ICF compartment disrupted, hyperkalemia was most effectively treated
      using mineralocorticoids, loop diuretics, and ion exchange resins to enhance
      elimination. In addition, i.v. calcium, glucose, insulin, and sodium bicarbonate
      were administered, which helped redistribute potassium to the ICF. Severe
      rhabdomyolysis should be included in the differential diagnoses of hyperkalemia,
      hyponatremia, hypocalcemia, and hyperphosphatemia in neonatal foals.

PMID- 9595381
TI  - Nonsurgical transcatheter coil occlusion of patent ductus arteriosus in two dogs
      using a preformed nitinol snare delivery technique.

PMID- 9595380
TI  - Pseudohypophosphatemia in two dogs with immune-mediated hemolytic anemia.

PMID- 9595382
TI  - Trimethoprim-induced exacerbation of hyperkalemia in a dog with
      hypoadrenocorticism.

PMID- 9595383
TI  - Endothelin-converting enzyme in the human vasculature: evidence for differential
      conversion of big endothelin-3 by endothelial and smooth-muscle cells.
AB  - Our aim was to localize endothelin-converting enzyme (ECE) in human saphenous
      vein grafts and to quantify enzymic activity in cultured human endothelial and
      smooth-muscle cells. Immunoreactive ECE localized to the endothelium and
      infiltrating macrophages in vein grafts, but little or no immunoreactivity was
      detected within the media or proliferated smooth muscle of the occlusive lesion.
      Cultures of human umbilical vein endothelial cells were incubated with big
      endothelin-1 (ET-1) (10 nM) to measure extracellular conversion. After 2 h the
      concentration of mature peptide in the medium was increased by 162.7 +/- 21.6 pM
      (n = 3 +/- SEM) above basal. Permeabilization of the cells increased conversion
      to 1077.9 +/- 52.8 pM, suggesting that about 85% of ECE activity was located
      intracellularly. In both cases, activity was inhibited by phosphoramidon but not
      by thiorphan. In contrast, conversion of big ET-3 (10 nM) under the same
      conditions was not detected in either intact or permeabilized cells after 2 h.
      Big ET-3 and big ET-1 were converted by a phosphoramidon-sensitive/thiorphan
      insensitive enzyme on the surface of confluent cultures of human umbilical vein
      smooth-muscle cells, with concentrations of the corresponding mature peptides
      increasing by 99.5 +/- 14.5 pM and 222.2 +/- 11.6 pM, respectively. These results
      suggest that smooth-muscle cells could be responsible for the synthesis of ET-3
      present in plasma and for additional processing of big ET-1 released by
      endothelial cells.

PMID- 9595384
TI  - Glycosylation of Asn-632 and Asn-651 is important for functional expression of
      endothelin-converting enzyme-1.
AB  - It has been shown previously that N-glycosylation of Asn-144 and/or Asn-627 is
      important for functional expression of neutral endopeptidase-24.11 (NEP). All
      glycosylation sites of NEP are conserved within endothelin-converting enzyme-1
      (ECE-1). In the present study we investigated the importance of proper
      glycosylation for the biologic function of ECE-1. We show that the double
      mutation of Asn-632 and Asn-651 leads to expression of an enzymatically inactive
      ECE-1 protein. In contrast, the single mutation of either Asn-632 or Asn-651 did
      not alter the enzymatic activity of ECE-1b.

PMID- 9595385
TI  - Human endothelin-converting enzyme-1 beta mRNA expression is regulated by an
      alternative promoter.
AB  - The central step in endothelin biosynthesis is site-specific cleavage of big
      endothelins by endothelin-converting enzymes (ECEs). ECE-1 is a membrane-bound
      metalloprotease, predominantly but not exclusively expressed in endothelial
      cells. ECE-1 is expressed in two mRNA isoforms, termed alpha and beta, which
      differ only in the 5'-terminal regions but are functionally very similar when
      expressed in vitro. The structure of the human ECE-1 gene suggests either
      alternative splicing or alternative promoters as underlying mechanisms of mRNA
      isoform expression. We have previously shown that the alpha-upstream region
      exerts promoter activity in endothelial cells. To clarify whether the 5'
      untranslated region upstream of exon 3, which contains the beta-specific
      sequence, acts as an alternative transcriptional promoter, we sequenced and
      cloned 1,206 bp upstream of the beta-specific translation initiation codon in a
      luciferase reporter vector. After transfection, we detected strong promoter
      activity in primary cultured endothelial cells (HU-VECs, BAECs) but only marginal
      activity in the endothelial cell line ECV304 and in CHO cells. Maximal promoter
      activity was observed with the full-length construct, 1206 (136% of the SV40
      promoter activity in BAECs). Transfection of serial deletion mutants indicated at
      least three major regulatory regions within the promoter. Our results are
      consistent with cell type-restricted action of the beta-promoter and, in
      conjunction with the previously reported transcriptional start sites, clearly
      prove the existence of an alternative beta-specific promoter located in intron 2
      of the human ECE-1 gene.

PMID- 9595386
TI  - Effects of dual endothelin-converting enzyme/neutral endopeptidase inhibitors,
      CGS 26303 and CGS 26393, on lipopolysaccharide or interleukin-1 beta-stimulated
      release of endothelin from guinea pig tracheal epithelial cells.
AB  - A number of studies using endothelin (ET) receptor antagonists support the
      participation of ETs in a variety of cardiovascular, renal, and other disorders.
      It has also been established that a number of cytokines, which are released in
      such diseases, modulate the expression and production of ETs and thus activate
      the ET system. This effect may represent one pathway by which these inflammatory
      mediators operate. By regulating endothelin-converting enzyme (ECE) activities,
      and thus ET synthesis, one can potentiate or attenuate the production of ETs and
      the receptor affinity/density in such pathologic conditions. Here, the stimulated
      (lipopolysaccharide or interleukin-1 beta) production of ET-1 from guinea pig
      tracheal epithelial cells was abolished by CGS 26303 or CGS 26393, two
      ECE/neutral endopeptidase (NEP) inhibitors, but was unaffected by CGS 24592, a
      specific NEP inhibitor. Therefore, such dual, and eventually selective ECE
      inhibitors are effective agents to prevent the stimulated production of ETs.

PMID- 9595387
TI  - The processing pathway of endothelin-1 production.
AB  - Production of endothelin (ET-1) is believed to be a three-step process,
      consisting of an initial proteolytic cleavage by signal peptidase of preproET-1,
      a second cleavage of proET-1 to big ET-1-Lys-Arg by dibasic amino acid-specific
      convertase and C-terminal trimming, and finally the processing of Big ET-1 to ET
      1 by endothelin-converting enzyme (ECE). To clarify the relationships between the
      second processing step and the third, we introduced point mutation into ET-1 cDNA
      to replace the Arg in the -4 position of the recognition motifs of furin-like
      convertase in human preproET-1 (Arg49 or Arg89) by Gly. When mutant cDNAs were
      expressed in CHO-K1 cells, they failed to be processed at the mutated processing
      signal, suggesting the involvement of the enzyme with furin-like specificity in
      the processing at dibasic amino acid motifs. Co-transfection of mutant preproET-1
      cDNA and ECE-1 cDNA revealed that cleavage at Arg92 is essential for cleavage by
      ECE-1 but that cleavage at Arg52 is not. Although without cleavage at Arg52 a
      high molecular weight form of ET-1, designated Large ET-1, is produced by
      processing by ECE-1, it did not evoke a Ca2+ transient in ETA receptor-expressing
      cells. In conclusion, the cleavage by furin-like convertase is essential for the
      production of active ET-1.

PMID- 9595388
TI  - Differential inhibition of wild-type endothelin-converting enzyme-1 and its
      mutants.
AB  - The purpose of this study was to determine the effect of mutation of rat
      endothelin-converting enzyme-1 (ECE-1) on the potencies of various inhibitors.
      The two amino acids mutated were Cys(412), which was shown to link the two
      monomeric enzymes to form a dimer, and Glu(752), postulated to be involved in
      substrate and inhibitor binding. No significant effects were noted when Glu(752)
      was replaced by an acidic (E752D) or uncharged (E752Q) residue. Replacing
      Glu(752) by a basic residue (E752R) slightly weakened the potencies of the
      inhibitors. In contrast, a significant decrease in the potencies was observed
      with the monomeric enzyme C412S. Phosphoramidon inhibited the wild-type ECE-1
      with an IC50 of 1.5 microM, but it was about sixfold weaker for the C412S mutant.
      CGS 31447, an aminophosphonic acid, inhibited the wild-type and C412S enzymes
      with IC50 values of 5.8 and 76 nM, respectively. A similar degree of change in
      the potencies was also seen with CGS 25015, a thiol-containing compound, which
      inhibited the respective enzymes with IC50 values of 17 and 190 microM. These
      results suggest that the charge in Glu(752) may not be important for inhibitor
      binding and that the dimeric ECE-1 is more susceptible to inhibition than the
      monomeric enzyme.

PMID- 9595389
TI  - Endothelin peptide and converting enzymes in human endothelium.
AB  - Sites linked to the storage and transportation of endothelin (ET) were
      investigated in human coronary artery. ET-like immunoreactivity was detected in
      secretory vesicles and storage granules, indicating that the peptide may be
      transported via both constitutive and regulated secretory pathways. The
      distribution of ECE-like immunoreactivity was also investigated to determine
      possible sites involved in the cleavage of big ET-1 to ET-1. Sections of coronary
      artery labeled with antisera raised against the endothelin-converting enzymes
      (ECE-1 alpha, ECE-1 beta, and ECE-2) showed immunoreactive staining over luminal
      endothelial cells. An en face coronary artery preparation labeled with antisera
      raised against ECE-1 alpha and ECE-1 beta revealed only a low level of plasma
      membrane staining by scanning electron microscopy. The findings indicate cell
      surface and intracellular expression of ECE in human endothelium.

PMID- 9595391
TI  - Immunohistochemical localization of endothelin-1 and endothelin-converting enzyme
      1 in rat lung allografts.
AB  - Chronic rejection is one of the principal factors that lead to development of
      obliterative bronchiolitis, which is the cause of death for 50% of lung allograft
      recipients. To more fully comprehend the pathogenesis of chronic rejection, we
      investigated the expression of endothelin-1 (ET-1) and endothelin-converting
      enzyme-1 (ECE-1) in inadequately immuno-suppressed rat lung allografts (n = 15)
      at monthly intervals after transplantation and compared these findings with those
      in normal rat lung (n = 5), using immunohistochemistry. Throughout the
      posttransplantation period, inflammatory cells expressed weak to moderate
      immunoexpression for both peptides. Constant weak to moderate immunoexpression
      for both peptides was also seen in the alveolar epithelium and neovascularized
      endothelium. Early after transplantation the vascular endothelium demonstrated
      strong immunostaining compared with control sections. This immunostaining,
      however, was reduced to control levels at later stages of rejection. As rejection
      progressed, staining in the airway epithelium diminished to weak levels as
      compared with that in controls. These findings suggest a causal role for ET-1 and
      ECE-1 in the inflammatory and proliferative damage associated with chronic
      rejection after lung transplantation.

PMID- 9595390
TI  - Enhanced endothelin-converting enzyme immunoreactivity in early atherosclerosis.
AB  - Endothelin-1 (ET-1) is a 21-amino-acid local and circulating factor whose plasma
      concentrations are increased in advanced atherosclerosis. ET-1 is cleaved from a
      prohormone (big ET-1) by endothelin-converting enzymes (ECEs) into the
      biologically active mature form which mediates vasoconstriction and cell
      proliferation. This study was designed to test by immunohistochemistry the
      hypothesis that ECE is present locally in the neointima of atherosclerotic
      vessels. Two groups of rabbits, control (n = 6) and cholesterol-fed (1%
      cholesterol diet for 8 weeks; n = 6) were sacrificed. Aortas were excised and
      divided for determination of tissue ET-1 concentration by RIA and
      immunohistochemical analysis of ECE. Vascular wall ET-1 was increased in the
      atherosclerotic aorta (6.1 +/- 0.8 vs. 9.8 +/- 0.9 pg/mg protein; p < 0.05),
      whereas circulating ET-1 concentrations were similar in the two groups (3.8 +/-
      0.4 vs. 2.4 +/- 1.4 pg/ml). Immunostaining revealed the presence of ECE in
      endothelial and vascular smooth-muscle cells of the control group. Enhanced ECE
      immunoreactivity was present in atherosclerotic aortas, particularly in the
      neointimal macrophages and smooth-muscle cells. We conclude that local vascular
      wall, but not circulating ET-1, is increased in early atherosclerosis. In
      addition, ECE immunoreactivity is increased in early atherosclerosis and may
      therefore contribute to the generation of local ET-1 in early experimental
      atherosclerosis. These studies provide important insights into the regulation of
      ET-1 in early atherosclerosis, which may contribute to the elucidation of factors
      involved in the progression of atherosclerosis.

PMID- 9595392
TI  - Renal endothelin-converting enzyme in rats with congestive heart failure.
AB  - The expression and immunoreactivity of endothelin-converting enzyme (ECE) were
      examined in the renal tissue of rats with experimental congestive heart failure
      (CHF). Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that ECE
      mRNA was more abundant (about twofold) in the renal medulla than in the cortex.
      Induction of heart failure caused a significant enhancement in the expression of
      this key enzyme in the renal cortex of rats with compensated CHF (delta + 28%)
      and in animals with decompensated heart failure (delta + 58%). An identical trend
      was also observed in the renal medulla, although these increases were moderate
      compared to those in the cortex. Similar findings were observed with Western blot
      techniques applying two monoclonal antibodies to rat ECE (AEC32-236 and AEC27
      121). Taken together, these data suggest that upregulation of ECE is an important
      component in the activated renal ET system in CHF.

PMID- 9595393
TI  - Characterization of site-directed antisera against endothelin-converting enzymes.
AB  - Site-directed antisera have been developed against the two endothelin-converting
      enzyme-1 (ECE-1) isoforms cloned to date in humans, ECE-1 alpha and ECE-1 beta.
      Antisera were raised in rabbits against synthetic peptides corresponding to the
      deduced amino acid sequences that differ between ECE-1 alpha and ECE-1 beta.
      Antisera were highly selective for their corresponding antigen (titer 1 x 10(4))
      and did not detect ET-1 or big ET-1. Furthermore, no detectable crossreactivity
      was observed between the different site-specific antisera and the other
      immunizing peptides, suggesting that the antisera would be selective for ECE-1
      alpha and ECE-1 beta. Standard displacement curves have been developed to
      determine the levels of immunoreactive ECE-1 alpha and ECE-1 beta in solubilized
      microsomal fractions of human tissue. In conclusion, we have described the first
      production and characterization of site-directed antisera raised against ECE-1
      alpha and ECE-1 beta capable of discriminating between the two ECE-1 isoforms.
      Furthermore, using these antisera, we have found that ECE-1 alpha appears to be
      the predominant isoform in human tissue.

PMID- 9595394
TI  - Endothelin-1 and endothelin-converting enzyme-1 gene regulation by shear stress
      and flow-induced pressure.
AB  - Hemodynamic forces have been shown to modulate the expression of endothelin (ET
      1) and endothelin-converting enzyme (ECE-1) in endothelial cells. We have
      subjected E.A. hy 926 cells in culture to steady fluid shear stress with and
      without flow-induced pressure. The effect of combining these two mechanical
      forces on the expression of genes in the ET system was studied and the changes
      were compared to the mRNA levels in static culture. Analysis of total RNA by
      Northern blot analysis and RNAse protection showed that steady shear stress
      induced ET-1 gene expression three- to fourfold in this system. The same
      condition had little to no effect on altering expression of ECE-1 isoforms. A
      range of flow-induced pressure (80-160 mm Hg) was not able to further augment ET
      1 or ECE-1 gene expression. Overall, with the mechanical environment studied, we
      have been able to detect a predominant contribution of shear stress to altering
      the ET-1 gene in our system. Furthermore, this induction was independent of an
      alteration of ECE-1 gene levels, suggesting that these two genes have a different
      pattern of regulation by the same stimuli in this cell type.

PMID- 9595395
TI  - Physiologic shear stress suppresses endothelin-converting enzyme-1 expression in
      vascular endothelial cells.
AB  - Shear stress dilates blood vessels and exerts an antiproliferative effect on
      vascular walls. These effects are ascribed to shear stress-induced, endothelium
      derived vasoactive substances. Endothelin-converting enzymes (ECEs), the enzymes
      that convert big endothelin-1 (ET-1) to ET-1, have recently been isolated and the
      corresponding proteins have been termed ECE-1 and ECE-2. Furthermore, two
      isoforms of human ECE-1 have been demonstrated and termed ECE-1 alpha and ECE-1
      beta. In this study, to elucidate the role of ECE-1 under shear stress we
      examined the effect of physiologic shear stress on the mRNA expression of ECE-1
      and ET-1 in cultured bovine carotid artery endothelial cells (BAECs) and human
      umbilical veins (HUVECs), and also ECE-1 alpha mRNA expression in HUVECs. ECE-1
      mRNA expression was significantly downregulated by shear stress in 24 h, both in
      BAECs and HUVECs, in a shear stress intensity-dependent manner. The expression of
      ECE-1 alpha mRNA was also attenuated by shear stress in HUVECs. ET-1 mRNA
      expression showed a concordant decrease with ECE-1 mRNA expression. These results
      suggest that shear stress-induced gene regulation of ET-1 and ECE-1 mRNA
      expression can contribute to the decrease of ET-1 peptide level by shear stress.

PMID- 9595396
TI  - Studies of endothelin-converting enzyme in bovine endothelial cells and vascular
      smooth-muscle cells: further characterization of the biosynthetic process.
AB  - Endothelin-1 (ET-1) is synthesized by a number of cell types, including
      endothelial, epithelial, and smooth muscle cells. Initial biosynthesis occurs as
      a protein precursor, preproendothelin-1 (preproET-1). This is processed
      intracellularly to the inactive intermediate big ET-1, which is hydrolyzed by
      endothelin-converting enzyme (ECE) to generate ET-1, but the precise identity of
      the physiologically relevant ECE has yet to be confirmed. Although ET-1 is
      synthesized in the constitutive secretory pathway, many features of the selective
      processing of proET-1 are comparable to those of peptide hormones. We describe
      here experimental investigations aimed at defining the regulation of ET-1
      synthesis and its relationship to the biosynthesis of ECE.

PMID- 9595397
TI  - Comparison of the regulation of endothelin-2 and endothelin-converting enzyme-1 b
      [correction of beta] by forskolin and TNF-alpha in ACHN cells.
AB  - The effects on the expression and secretion of ET-2 of forskolin and tumor
      necrosis factor-alpha (TNF-alpha) were investigated using the human renal
      adenocarcinoma (ACHN) cell line. For comparison, changes in endothelin-converting
      enzyme-1 b (ECE-1 b) [corrected] mRNA were also determined. Treatment for 4 with
      TNF-alpha (3 ng/ml), forskolin (30 microM), or the combination caused significant
      increases in ET-2 release, TNF-alpha alone or in combination with forskolin
      increased ET-2 mRNA levels at 1 h and 2 h. After 4 h the expression of ET-2 mRNA
      was comparable to control levels. In contrast to ET-2, ECE-1 b [corrected] mRNA
      levels were increased by TNF-alpha only at 4 h. Forskolin increased expression of
      ET-2 mRNA at 1 and 4 but had no significant effect on expression of ECE-beta.
      These data suggest that expression of ET-2 and ECE-1 b [corrected] mRNA is
      regulated differently in ACHN cells.

PMID- 9595398
TI  - Endothelin-converting enzyme-1 mRNA expression in human cardiovascular disease.
AB  - Endothelin-converting enzyme-1 (ECE-1) plays a substantial role in activation of
      the endothelin (ET) system by cleaving the precursor, big ET-1, to the active
      peptide ET-1. The aim of this study was to investigate whether ECE-1 mRNA
      expression is modified in human cardiovascular disease. ECE-1 expression was
      related to echocardiographic data, drug treatment, age, sex, and NYHA heart
      failure classification. A quantitative PCR assay (qPCR) was established to
      measure ECE-1 mRNA in these samples. The ECE-1 measurements were normalized over
      a simultaneously performed GAPDH qPCR. The results indicate a higher ECE-1
      expression level in atrial tissue samples of patients who have experienced a
      myocardial infarction compared with those who did not (ECE-1/GAPDH: 5.81 +/- 0.76
      fg/ng; n = 21 vs. 3.20 +/- 0.51 fg/ng; n = 22; p = 0.007). The transverse
      diameter of the left atrium over 37 mm was associated with a lower ECE-1
      expression (ECE-1/GAPDH: 3.11 +/- 0.69 fg/ng; n = 18 vs. 5.12 +/- 0.65 fg/ng; n =
      25; p = 0.044). In assessing the drug treatment, decreased ECE-1 expression could
      be observed in patients who received a beta-blocker (ECE-1/GAPDH: 3.90 +/- 58
      fg/ng; n = 31 vs. 5.81 +/- 0.76 fg/ng; n = 12; p = 0.077). These data suggest an
      involvement of the ET system is cardiovascular disease that may be clinically
      important.

PMID- 9595399
TI  - Endothelial expression of endothelin-converting enzyme-1 beta mRNA is regulated
      by the transcription factor Ets-1.
AB  - Cleavage of big endothelins (ETs) by endothelin-converting enzymes (ECEs)
      represents the final step in the biosynthesis of ETs. ECE-1 is expressed
      predominantly in endothelial cells and exists in two isoforms, termed alpha and
      beta, differing in their 5' termini. We have recently shown that isoform-specific
      mRNA expression is directed by alternative promoters. To investigate possible
      mechanisms of transcriptional regulation of ECE-1, we stimulated E.A. hy 926
      cells with phorbol ester and found a greater than threefold increase in ECE-1
      beta mRNA at 12-24 h of stimulation. Because the beta-specific promoter is
      characterized by multiple consensus sequences for transcription factors of the
      ETS family, Ets-1 and PEA3, we also analyzed Ets-1 mRNA expression and found at
      least a fivefold increase in Ets-1 mRNA at 3 h of phorbol ester stimulation. Gel
      shift analysis revealed a specific interaction of nuclear proteins isolated from
      E.A. hy 926 cells with an oligonucleotide harboring the Ets-1 consensus sequence.
      Using a specific anti-Ets-1 antibody, we detected a supershifted band indicating
      the expression of Ets-1 protein in E.A. hy 926 cells. We conclude that Ets-1 is
      involved in transcriptional upregulation of ECE-1 beta mRNA in E.A. hy 926 cells
      induced by phorbol ester.

PMID- 9595400
TI  - Contractile activity of endothelins and their precursors in human umbilical
      artery and vein: identification of distinct endothelin-converting enzyme
      activities.
AB  - A number of studies using endothelin (ET) precursors, commonly termed big ETs,
      have revealed the presence of endothelin-converting enzyme (ECE) activity in
      various vascular and nonvascular preparations. Since then, more than one ECE has
      been cloned. It has also been observed that big ET-1 and big ET-3 are not
      converted by the same enzyme. The ECE responsible for big ET-3 conversion is
      rarely present because big ET-3 does not induce a contractile response in most
      isolated preparations tested. In this study we characterized ECE activities
      present in two human preparations, the umbilical artery and vein, testing the
      contractile activities of the three human Big ETs in the presence or absence of
      phosphoramidon, a dual ECE/neutral endopeptidase inhibitor. The results show that
      human big ET-1(1-38) is 6.3-fold more potent than big ET-2(1-38) in the human
      umbilical artery (an ETA preparation), whereas big ET-1 is equipotent to big ET-2
      in the vein (which contains ETA and ETB receptors). Human big ET-3(1-41) is
      inactive on both vessels. Furthermore, phosphoramidon attenuated human big ET-1
      induced contractions only in the umbilical artery and not in the vein. Such
      observations, in terms of substrate selectivity and phosphoramidon sensitivity,
      suggest the presence of distinct ECE activities in human vein and arteries.

PMID- 9595401
TI  - Big endothelin analogues with inhibitory activity on endothelin-converting enzyme
      1.
AB  - Big endothelin-1 (big ET-1) is converted into an active form, ET-1, by endothelin
      converting enzyme-1 (ECE-1). To assess the mechanism of substrate recognition by
      ECE-1, we examined the effects of variously substituted analogues of big ET-1 on
      ECE-1 activity, using solubilized membranes prepared from human ECE-1-expressed
      CHO-K1 cells. Among the big ET-1 analogues tested, [21Phe]big ET-1[18-34] and
      [31Ala]big ET-1[18-34] exhibited significant inhibition of ECE-1. A kinetic
      analysis revealed [21Phe]big ET-1[18-34] to be a competitive inhibitor (Ki = 21
      microM) and [31Ala]big ET-1[18-34] to be a noncompetitive inhibitor (Ki = 36
      microM). These results suggested that ECE-1 recognizes big ET-1 at the P1
      position and the C-terminal region in a different manner and that modification of
      these regions can produce ECE-1 inhibitors.

PMID- 9595402
TI  - Evidence for functional endothelin-converting enzyme activity in isolated rat
      basilar artery: effect of inhibitors.
AB  - Endothelin-1 (ET-1) may be involved in the upregulation of cerebroarterial
      resistance under pathologic conditions, most notably in the development of
      vasospasm after subarachnoid hemorrhage. Therefore, blocking the contractile
      action of ET-1 by receptor antagonists may prove to be a new and worthwhile
      approach. However, decreasing synthesis and release of ET-1 by blocking the
      endothelin-converting enzyme (ECE) activity may also prove worthwhile. In this
      study we have therefore investigated the effect of several putative ECE
      inhibitors in isolated rat basilar artery by measuring isometric contraction
      after application of big ET-1, the precursor peptide which is not vasoactive in
      itself. In the presence of phosphoramidon (10(-4) M in segments with an intact
      endothelium or 5 x 10(-4) M in de-endothelialized segments), there was only a
      small shift to the right of the concentration-effect curve for big ET-1.
      Similarly, 10(-3) M thiorphan (a selective inhibitor of the neutral
      endopeptidase) did not affect big ET-1-induced contraction, both alone and in
      combination with phosphoramidon (10(-3) M). When the big ET-1 analogue [22Phe]big
      ET-1[19-37] was applied, an increase in resting tension occurred irrespective of
      whether or not the endothelium was present. Furthermore, in the presence of 10(
      5) M [22Phe]big ET-1[19-37], contraction induced by big ET-1 was not affected in
      de-endothelialized segments but rather was enhanced in endothelium-intact
      segments. These results suggest the presence of functional ECE activity in the
      rat basilar artery wall. However, such activity could not be markedly inhibited
      with different putative enzyme inhibitors. Therefore, the chemical nature of the
      cerebroarterial ECE activity must be further elucidated before rational
      development of efficient ECE inhibitors for treatment of cerebral vasospasm
      becomes possible.

PMID- 9595403
TI  - Characterization of CGS 31447, a potent and nonpeptidic endothelin-converting
      enzyme inhibitor.
AB  - Optimization of an aminophosphonic acid series of compounds for inhibition of
      endothelin-converting enzyme (ECE) has led to the discovery of CGS 31447. This
      compound reversibly inhibited the activity of recombinant human ECE-1 with an
      IC50 value of 21 nM. The effect of CGS 31447 was not due to nonspecific chelation
      of the zinc ion at the catalytic center of ECE-1 by the phosphonic acid of the
      inhibitor. Determination of kinetic parameters of ECE-1 in the presence of 5-15
      nM CGS 31447 revealed the competitive nature of the compound; a K1 of 7 nM was
      obtained. CGS 31447 infused at concentrations of 0.01, 0.1, and 1.0 microM
      inhibited the mean increase in big ET-1-induced pressor responses in isolated and
      perfused rat kidneys by 7, 39, and 68%, respectively, compared with the controls.
      These results demonstrate that CGS 31447 is a potent, reversible, and competitive
      inhibitor of ECE-1.

PMID- 9595404
TI  - Benzofused macrocyclic lactams as triple inhibitors of endothelin-converting
      enzyme, neutral endopeptidase 24.11, and angiotensin-converting enzyme.
AB  - The purpose of this study was to identify endothelin-converting enzyme (ECE)
      inhibitors that also possess inhibitory activity for neutral endopeptidase 24.11
      (NEP) and angiotensin-converting enzyme (ACE). The ortho-substituted benzofused
      macrocyclic lactams, such as CGS 26670, are generally potent NEP inhibitors but
      poor ACE inhibitors. CGS 26670 inhibited ECE activity with an IC50 of 600 nM,
      whereas it inhibited NEP and ACE activities with IC50 values of 0.9 and > 10,000
      nM, respectively. This compound also prevented the conversion of big endothelin-1
      (big ET-1) to ET-1 by denuded porcine coronary arterial smooth muscle with an
      IC50 of 200 nM. The ACE inhibitory activity is greatly is greatly improved in
      metasubstituted benzofused macrocyclic lactams. For example, CGS 26582 inhibited
      ECE, NEP, and ACE activities with IC50 values of 620, 4, and 175 nM,
      respectively. When injected at 30 mg/kg i.v. in conscious rats, followed by a
      challenge with big ET-1 at 1 nmol/kg i.v., this compound suppressed by 44% the
      increase in mean arterial blood pressure owing to the generation of ET-1 by ECE.
      Because ECE, NEP, and ACE play regulatory roles in cardiovascular and renal
      function, triple inhibitors of these enzymes may represent a novel class of
      agents for treatment of cardiovascular and renal diseases.

PMID- 9595405
TI  - Relative contribution of endothelin A and endothelin B receptors to
      vasoconstriction in small arteries from human heart and brain.
AB  - Endothelin (ET) has been implicated in cardiovascular disorders such as stroke
      and myocardial ischemia. Given the important role of the resistance vasculature
      in the control of blood flow, we investigated the ET receptors that mediate
      vasoconstriction in human small pial and coronary arteries supplying the brain
      and heart, respectively. ETA receptors were localized by autoradiography to the
      vascular smooth-muscle layer of pial, intracerebral, and intramyocardial
      arteries. In contrast, little ETB binding was observed. ET-1 was a more potent
      constrictor than ET-3 in both pial and coronary arteries. Biphasic ET-3 responses
      were obtained in four of 15 coronary arteries tested. The ETB agonist sarafotoxin
      S6c had little or no effect in these vessels. The nonpeptide, selective ETA
      receptor antagonist PD156707 caused a parallel shift to the right of the
      concentration-response curve to ET-1, yielding pA2 values of 9.17 +/- 0.07 and
      8.38 +/- 0.17 in pial and coronary arteries, respectively. Slopes from Schild
      analysis were not significantly different from unity. These data suggest that ETA
      receptors predominate on the smooth-muscle layer of human small pial arteries.
      Coronary arteries also express mainly ETA receptors. However, a small population
      of contractile ETB receptors may also be present in some patients.

PMID- 9595406
TI  - Dynamic regulation of beta-adrenergic receptors by endothelin-1 in smooth-muscle
      cells.
AB  - Elevated endothelin-1 (ET-1) levels are found in atherosclerosis, myocardial
      ischemia, and heart failure, and are correlated with increased mortality rates.
      Contrary to expectations, elevations of endogenous ET-1 levels in transgenic mice
      are not associated with increases in arterial blood pressure or with vasospasm,
      although these effects can be observed after i.v. ET-1 administration. The aim of
      this study was to determine the regulatory effects of ET-1 on the expression of
      vasodilator beta-adrenergic receptors and their ability to activate adenylyl
      cyclase. Smooth-muscle cells were incubated with ET-1 (10(-7) mol/L) for 3 days.
      The density of ET-1 or beta-adrenergic receptor binding sites was determined
      using a radioligand binding procedure. Adenylyl cyclase activity was measured to
      assess any functional changes in the beta-adrenergic receptor density. ET-1
      incubation reduced ET-1 binding sites by 70%. In contrast, the beta-adrenergic
      receptor density increased from 354 +/- 35 to 538 +/- 50 fmol/mg protein (p <
      0.01; n = 7) after 3 days. ET-1 increased beta-adrenergic receptors dose
      dependently. Incubation with ET-1 for different periods of time showed an initial
      decrease of 30% after 6 h of ET-1 incubation. However, after 24 h ET-1 induced an
      increase of beta-adrenergic receptors, reaching a maximal amount after 48 h. An
      increased stimulation of beta-adrenergic receptor-activated adenylyl cyclase was
      observed after 3-day ET-1 incubation compared to controls. These data demonstrate
      that chronic ET receptor activation by ET-1 results in a functionally significant
      increase in beta-adrenergic receptor density and adenylyl cyclase activity.

PMID- 9595407
TI  - Endothelin-1, delayed rectifier K channels, and pulmonary arterial smooth muscle.
AB  - Sarafotoxin S6c [STXS6c; a selective endothelin-B (ETB) receptor agonist] causes
      constriction of isolated pulmonary arteries. In perforated-patch experiments on
      pulmonary arterial myocytes, ET-1 and STXS6c induced a gradual inhibition of the
      delayed rectifier K current (IKV), the profile of which resembled that carried by
      Kv1.5. Reverse-transcriptase polymerase chain reaction (RT-PCR) experiments
      revealed mRNA encoding this channel, and immunolocalization experiments
      demonstrated expression of the channel protein in pulmonary arterial smooth
      muscle. It is tempting to speculate that ETB receptor coupling to Kv1.5 may be
      implicated in contraction after stimulation of these receptors.

PMID- 9595408
TI  - Effect of the endothelin family of peptides on human coronary artery smooth
      muscle cell migration.
AB  - The migration of coronary artery medial smooth-muscle cells (SMCs) is one of the
      key events in the process of intimal thickening in coronary atherosclerotic
      lesions. The objectives of the present study were to determine whether any of the
      three isoforms of endothelin (ET), ET-1, ET-2, and ET-3, or an intermediate form
      of ET, big ET-1, induces migration of human coronary artery SMCs, and to
      investigate the possible interaction of ET peptides and well-known migration
      stimulatory factors, platelet-derived growth factor (PDGF)-BB and angiotensin II
      (Ang II), on SMC migration by the Boyden's chamber method. None of the ET
      peptides alone induced SMC migration between 10(-9) and 10(-7) mol/L. In
      contrast, ET-1 and ET-2 significantly induced SMC migration in the presence of
      low concentrations of PDGF-BB (0.5 ng/mL) or Ang II (10(-9) mol/L), although ET-3
      was less active (ET-1 = ET-2 > ET-3). In contrast, big ET-1 was without
      significant activity on PDGF-BB-or Ang II-induced SMC migration. The potentiation
      of SMC migration by ET peptides was clearly inhibited by the ETA receptor
      antagonist BG-123 in a concentration-dependent manner. These results suggest that
      the ET family of peptides, especially ET-1 and ET-2, can induce human coronary
      artery SMC migration in combination with PDGF-BB or Ang II, probably via ETA
      receptors. Taken together with the finding that the concentrations of ET, PDGF-BB
      and Ang II are locally increased at sites of endothelial injury, this indicates
      that ET may be an initial stimulus for human coronary artery medial SMC
      recruitment during coronary atherosclerosis, possibly in combination with PDGF-BB
      or Ang II.

PMID- 9595409
TI  - Comparison of circulating endothelin-1 and big endothelin-1 levels in unstable
      versus stable angina pectoris.
AB  - The pathophysiologic meaning of elevated circulating endothelin-1 (ET-1) levels
      in various cardiovascular diseases is not understood. The aim of this study was
      to measure ET-1 and big ET-1 levels in patients with unstable angina pectoris
      (UAP) and within 5 days after stabilization. These values were compared to those
      of patients with stable angina pectoris (SAP) and to healthy controls (Co). In
      addition, a venous occlusion test was performed as an endothelial provocation
      test to characterize endothelial function. Big ET-1 levels were increased to 2.6
      +/- 1.5 fmol/ml during unstable angina pectoris compared to normal values of 0.52
      +/- 0.07 fmol/ml (p < 0.03; n = 14). After stabilization, big ET-1 decreased to
      1.5 +/- 0.4 fmol/ml within 5 days (n.s.). ET-1 levels were not increased during
      UAP and after stabilization. ET-1 and big ET-1 levels from patients with SAP did
      not differ from those of healthy controls. The venous occlusion test resulted in
      an increase of ET-1 levels (0.3 +/- 0.02 to 0.46 +/- 0.02 fmol/mg, p = 0.008; SAP
      0.3 +/- 0.04 to 0.39 +/- 0.05 fmol/ml, p = 0.009) in healthy controls and in
      patients with SAP. In contrast, patients with UAP showed no significant increase
      in ET-1 with this test. After stabilization for 5 days, the provocation test
      induced an increase in circulating ET-1 in patients with UAP comparable to that
      of controls (0.62 +/- 0.18 fmol/mg vs. 0.95 +/- 0.25 fmol/mg; p < 0.02). In
      summary, during UAP big ET-1 values are significantly increased and ET-1 values
      tend to be elevated. In an endothelial provocation test, ET-1 values did not
      increase. This might reflect a general activation of the endothelium in UAP
      during the acute stage, because the normal response is recovered 5 days later.

PMID- 9595410
TI  - Augmented response of endothelin-A and endothelin-B receptor stimulation in
      coronary arteries of hypertensive hearts.
AB  - To determine whether the vasoconstrictor response to endothelin-1 (ET-1) is
      altered in coronary vessels of hypertensive hearts and the role of ETA and ETB
      receptors in these responses to ET-1, the vasoconstrictor response to ET-1 in
      coronary vessels was measured with or without ETA and ETB receptor antagonists.
      In isolated hearts of spontaneously hypertensive rat (SHR) and normotensive
      Wistar-Kyoto (WKY) rat, the coronary perfusion pressure was measured on a
      Langendorff apparatus with constant pressure (75 mm Hg). Coronary perfusion
      resistance (CPR) (mm Hg/ml/min/g) was calculated. ET-1 elicited dose-dependent
      increases of CPR in both normotensive and SHR rat hearts. However, the responses
      were significantly greater in SHR than those of WKY. Pretreatment with the ETA
      antagonist FR139317 and the ETB antagonist BQ788 inhibited CPR increases with ET
      1 infusion. However, vasoconstrictor responses to ET-1 were still greater in SHR
      than in WKY after FR139317 or BQ788 infusion. These findings suggest that the
      augmented vasoconstrictor response of coronary artery to ET-1 is mediated by both
      ETA and ETB receptors. These changes may contribute to the impaired coronary
      circulation in hypertension.

PMID- 9595411
TI  - SB 209670 inhibits the arrhythmogenic actions of endothelin-1 in the anesthetized
      dog.
AB  - SB 209670 reduced basal mean arterial pressure (16%) without affecting left
      circumflex coronary artery (LCX) flow, cardiac output, heart rate, or
      global/regional myocardial contractility. In vehicle-treated animals, i.e.
      endothelin (ET)-1 produced an initial hyperemic response in the LCX, followed by
      a secondary reduction in flow. This response was accomplished by decreases in LCX
      regional wall fractional shortening, +dP/dt and -dP/dt, but an increase in left
      anterior wall fractional shortening. ET-1 also produced dose-related, fatal
      ventricular fibrillation. Whereas SB 209670 administration did not inhibit the
      initial increase in coronary flow produced by ET-1, the secondary constrictor
      responses were markedly antagonized. SB 209670 also attenuated the reduction in
      LCX regional wall fractional shortening and converted the increase in left
      anterior wall contractility to a reduction in contractility. Although SB 209670
      produced only a modest inhibition of the ET-1-mediated reductions in dP/dt, the
      induction of fatal ventricular arrhythmias was completely abolished. Therefore,
      the data are consistent with the hypothesis that the coronary ischemic and
      proarrythmic actions of ET-1 are distinct. Therefore, ET receptor antagonists may
      be useful in treatment of disturbances in cardiac rhythm.

PMID- 9595412
TI  - Endothelin does not interact with angiotensin II in the coronary vascular bed of
      anesthetized dogs.
AB  - We postulated that individually subthreshold circulating levels of angiotension
      II (Ang II) and endothelin-1 (ET-1) might induce fulminant coronary
      vasoconstriction when both are present. In 16 pentobarbital-anesthetized, open
      chest mongrel dogs, blood pressure, heart rate, and standard ECG were registered
      continuously. Coronary blood flow (CBF) was measured in the left anterior
      descending coronary artery (LAD) by an electromagnetic flow probe. Drugs were
      administered into the LAD via an indwelling catheter. Bolus injections of Ang II
      (7.8 x 10(-13) to 3.9 x 10(-11) M) and ET-1 (10(-12) to 10(-9) M) induced a dose
      dependent decrease in CBF (delta CBFmax -82 +/- 10% for Ang II and -91 +/- 8% for
      ET-1). Simultaneous Ang II and ET-1 boluses had slightly smaller effects on CBF
      than the calculated additive figure. Five-minute infusions of Ang II (10(-12) to
      10(-10) M/min) and ET-1 (5 x 10(-12) to 2 x 10(-10) M/min) induced a slight
      decrease in CBF (delta CBFmax -12 +/- 9% for Ang II and -19 +/- 9% for ET).
      Background ET-1 or Ang II infusions did not alter the dose-response curve of the
      other drug. Simultaneous Ang II and ET-1 infusions at different rates (10(-12) to
      10(-10) M/min for Ang II and 5 x 10(-12) to 2 x 10(-10) M/min for ET-1) over 5
      min had similar effects on CBF as the calculated additive figure (delta CBFmax 
      35 +/- 17% for the joint administration of the highest doses). We conclude that
      after simultaneous administration into the dog coronary artery, Ang II and ET-1
      do not interact sufficiently to induce fulminant vasoconstriction.

PMID- 9595414
TI  - L-NAME potentiates endothelin-stimulated thromboxane release from guinea pig
      lung.
AB  - The bronchoconstrictor response after systemic administration of endothelins
      (ETs) in the guinea pig is indirectly mediated by thromboxane A2 (TxA2) release
      through ETB receptor activation. ETs also trigger the release of nitric oxide
      (NO) in endothelial cells by activation of ETB receptors. A growing body of
      evidence indicates that endogenous NO plays a key role in the regulation of
      pulmonary function. In this study we investigated the effect of an NO synthase
      inhibitor, L-NAME, on the release of TxA2 from the isolated, perfused guinea pig
      lung induced either by ET-1, the selective ETB receptor agonist IRL-1620,
      bradykinin (BK), or a TxA2-mimetic, U 46619. A 30 min intra-arterial (intra
      arterial) infusion of L-NAME (300 microM) potentiated the TxA2 release with ET-1,
      IRL 1620, and BK (5, 50, and 50 nM, respectively) infused for 3 min (i.a.). U
      46619 (10 nM) was ineffective as a stimulant of pulmonary eicosanoid release.
      Interestingly, L-NAME did not potentiate the release of prostacyclin (PGI2)
      triggered by ET-1, IRL 1620, or BK. Our results suggest a predominant role of ETB
      receptor activation in the release of TxA2. Furthermore, we suggest that NO in
      the guinea pig lung is a potent modulator of the TxA2 releasing activity of ET-1,
      IRL 1620, and BK, three agonists known to stimulate the release of NO.

PMID- 9595413
TI  - Compensation of endothelin-1-induced coronary vasoconstriction.
AB  - The vasodilator capacity of the coronaries was determined by the reactive
      hyperemia (RH) test in open-chest anesthetized dogs. The myocardial release of
      adenine nucleosides (adenosine and inosine) was measured by the HPLC-UV method.
      In group I (n = 9) after the control RH test, a bolus injection of endothelin-1
      (ET-1; 1.0 nmol i.c.) was administered and was followed by a second RH test. In
      group II (n = 9), glibenclamide (GLIB) was infused continuously (1.0 mumol/min
      i.c.) and RH tests were performed during the control period and then before and
      after bolus injection of ET-1. In contrast to the significant reduction of the RH
      response after ET-1 in group I and after GLIB in group II, the nucleoside release
      into the coronary sinus during the first minute of the RH test was significantly
      higher (adenosine release 0.05 +/- 0.02 vs. 0.10 +/- 0.04 mumol, and 0.02 +/-
      0.00 vs. 0.08 +/- 0.02 mumol; p < 0.05). Injection of ET-1 did not result in
      further RH reduction in GLIB-pretreated dogs (group II) but significantly
      increased nucleoside release. High doses of ET-1 activated the metabolic
      compensatory mechanisms of the myocardium and thereby increased the release of
      adenine nucleosides into the venous blood of the heart. However, whether these
      metabolites can exert any significant compensatory vasodilator effects appears
      doubtful.

PMID- 9595415
TI  - Endothelin-1 modulation of cAMP in rat pulmonary arteries: effect of chronic
      hypoxia.
AB  - The effect of hypoxic shock on the ability of endothelin (ET) receptors to
      interact with the cAMP second messenger system was assessed in rat pulmonary
      arteries. Whole pieces of tissue were dissected from the pulmonary arterial
      system of control and hypoxic (10% O2, 14 days) rats, incubated, where
      appropriate, with ET-1 (0.1 microM), and the levels of intracellular cAMP
      measured. Maintenance of rats under hypoxic conditions significantly reduced the
      basal cAMP levels in all of the arterial branches with the exception of the
      pulmonary resistance vessels, in which no change was observed. Incubation of the
      main and first branch extralobar pulmonary arteries from control rats with ET-1
      resulted in a consistent decrease in the levels of intracellular cAMP. The ETA
      receptor antagonist FR139317 partially blocked this ET-1-mediated inhibition of
      cAMP accumulation in the main extralobar artery. In contrast, ET-1 caused a
      threefold increase in the levels of this cyclic nucleotide in the pulmonary
      resistance vessels from the normoxic rat. No ET-1-mediated reduction in
      intracellular cAMP levels was observed in any of the vessels isolated from
      hypoxic animals. All vessels showed ligand-activated increases in cAMP
      production. These results suggest differential modulation of cAMP in the
      different pulmonary arteries, either by direct activation through Gi and Gs or
      indirectly via a uncharacterized cross-talk mechanism.

PMID- 9595416
TI  - Heterogeneity of endothelin-B receptors in rabbit pulmonary resistance arteries.
AB  - We have previously shown that endothelin-B (ETB) receptors mediate contraction in
      human and rat pulmonary resistance arteries (PRAs). Here we characterize the
      endothelin (ET) receptors in rabbits PRAs. PRAs (approximately 150 microns i.d.)
      were studied using wire myography. Vasoconstrictor effects to ET-1, ET-3, and the
      ETB-selective agonist sarafotoxin S6c (S6c) were studied in the presence and
      absence of the ETA receptor antagonist FR139317, the ETB-selective antagonist
      BQ788, and the mixed ETA/ETB antagonist SB209670. The effect of SB209670 was also
      studied in human PRAs (approximately 250 microns i.d.). Competitive ET-1 binding
      studies were also carried out on rabbit small pulmonary artery homogenates. The
      potencies of the agonists were in the following order: S6c > ET-3 = ET-1.
      Concentration-response curves (CRCs) to ET-1 were biphasic, with a gradual slope
      up to approximately 1 nM and a steeper component at higher concentrations of ET
      1. Neither FR139317 (1 microM) nor BQ788 (1 microM) inhibited responses to ET-1.
      BQ788 inhibited S6c- and ET-3 induced contractions with pKb values of 6.8 +/- 0.1
      and 6.3 +/- 0.2, respectively. SB209670 inhibited responses to ET-1 in the higher
      concentration component of the CRC and inhibited responses to S6c in a
      competitive fashion. pKb values for ET-1 and S6c were 6.8 +/- 0.2 and 7.5 +/- 1,
      respectively. SB209670 (0.1-1 microM) totally abolished responses to ET-1 in
      human PRAs. The binding assay established two ET binding sites in rabbit PRAs,
      one low affinity (Ki = 480 pM) and one high affinity (Ki = 64 fM). The study
      provides evidence for a heterogeneous population of ETB-like receptors in
      pulmonary resistance arteries, including an atypical ETB receptor sensitive to
      SB209670.

PMID- 9595417
TI  - Endothelin-1 enhances pressor responses to norepinephrine: involvement of
      endothelin-B receptor.
AB  - We investigated the effects of endothelin-1 (ET-1) on pressor responses to
      norepinephrine (NE) in perfused rat mesenteric arteries. Perfusion of the
      arteries with a subpressor dose of ET-1 (3 x 10(-10) M) for 15 min markedly
      enhanced the pressor responses to NE (10(-6) and 3 x 10(-6) M), and this effect
      was significantly prevented by BQ788 (10(-6) M) but not by FR139317 (10(-6) M).
      In DOCA-salt hypertensive rats, exogenous ET-1 had little effect on pressor
      responses to NE. Pressor responses to NE (10(-6) M) were significantly increased
      in DOCA-salt rats compared with those in normotensive rats. This increased
      response to NE was reduced to the level of normotensive rats by BQ788. FR139317
      was without effect on the increased responses. These results suggest that ET-1
      enhances contractile responses to NE through ETB receptors. Moreover, this
      phenomenon is stimulated tonically by endogenous ET-1 in DOCA-salt hypertensive
      rats and may contribute to the maintenance of hypertension in these rats.

PMID- 9595418
TI  - Influence of endothelin-1 on clonidine-induced cardiovascular effects in
      anesthetized rabbits.
AB  - This study was designed to investigate the effect of endothelin-1 (ET-1) on
      clonidine-induced cardiovascular effects in urethane-anesthetized rabbits and to
      clarify the mechanism of its action. Clonidine (5, 10, and 20 micrograms/kg)
      given into a femoral vein (i.v.) produced a marked dose-dependent fall in
      arterial blood pressure and heart rate, but intracerebroventricular (i.c.v.)
      clonidine (2, 4, and 8 micrograms/kg) induced a slight depressor effect and
      bradycardia. Intravenous clonidine-induced hypotension was significantly enhanced
      by pretreatment with ET-1 or sarafotoxin, but the bradycardia was not affected.
      Intracerebroventricular clonidine-induced depressor responses were greatly
      inhibited by sarafotoxin pretreatment but not by ET-1. Both i.v. and i.c.v. ET-1
      and sarafotoxin elicited marked hypotensive responses, with a slight decrease in
      heart rate. The depressor action evoked by i.v. ET-1 and sarafotoxin was
      significantly inhibited by nitroprusside but not by phentolamine or sodium
      acetylsalicylate. Furthermore, the weak bradycardia induced by ET-1 or
      sarafotoxin was not influenced by pretreatment with phentolamine, nitroprusside,
      or sodium acetylsalicylate. Taken together, these experimental data suggest that
      ET-1 potentiates clonidine-induced hypotensive responses in the urethane
      anesthetized rabbit through facilitation of nitric oxide release, which appears
      to be associated with endothelin receptors.

PMID- 9595419
TI  - The role of endothelin-1 in regulation of rat mesenteric microcirculation.
AB  - Immunocytochemistry of endothelin-1 (ET-1) and the ETA receptor, and scanning
      electron microscopy using cast resin after treatment with ET-1, were carried out
      in the rat mesenteric microvasculature. Immunoreaction of ET-1 was preferentially
      seen along the endothelium of the proximal portion of the anterior mesenteric
      artery, the endothelial cells of which contain abundant Weibel-Palade (WP)
      bodies. However, the arterioles and small veins distal to the artery showed
      little immunoreactivity but showed heavy immunoreaction of ETA receptors in the
      media. By scanning electron microscopy after treatment with ET-1, the mesenteric
      microvasculature became slightly narrower compared to the control exhibited of
      localized constricted areas, especially in the region of the small veins. Light
      microscopy of such areas revealed localized thickening of the medial muscle
      cells. Because the release of ET-1 from endothelial cells depends in part on
      extracellular discharge of the WP bodies, the results indicate that ET-1,
      discharged from the proximal portion of the anterior mesenteric artery, induces
      vasoconstriction of the arterioles and small veins, mediated by ETA receptors.
      The localized thickening in areas in the media of the small veins may participate
      in the maintenance of blood flow through the portal circulation.

PMID- 9595420
TI  - Effects of endothelin-induced nitric oxide on venous circulation and renal water
      electrolyte handling.
AB  - To assess the interaction of endothelin (ET) with nitric oxide (NO) and the
      effects on venous circulation and handling of renal water and electrolytes, ET
      (1.0 ng/kg/min) or saline was administered with or without three doses (0.27, 2.7
      and 27 ng/kg/min for 40 min) of N omega-nitro-L-arginine methyl ester (L-NAME),
      and NO synthase inhibitor, in anesthetized dogs. ET increased total peripheral
      resistance (TPR), pulmonary capillary wedge pressure (PCWP), urine flow (UF), and
      urinary K excretion (UKV), and decreased cardiac output (CO), urinary osmolality
      (Uosm), renal plasma flow (RPF), and glomerular filtration rate (GFR). L-NAME
      increased blood pressure (BP), TPR, PCWP, right atrial pressure (RAP), and mean
      circulatory filling pressure (MCFP), and decreased CO, RPF, and GFR, ET plus L
      NAME markedly increased TPR, resistance to venous return, and plasma atrial
      natriuretic peptide (ANP), but not BP and MCFP, and curtailed the ET-induced
      responses in UF, UKV, and Uosm. Plasma aldosterone (ALD) was decreased in all
      groups, but plasma vasopressin (AVP) and renin activity (PRA) were not altered in
      any group. These results indicate that ET-induced NO formation might mitigate
      increases in venous as well as arterial vascular resistance and changes in renal
      handling of water and electrolytes, and might also play an inhibitory role in ANP
      release but not in PRA or AVP and ALD release.

PMID- 9595421
TI  - Preferential reduction in vascular responses to endothelin-1 in rats with
      streptozotocin-induced diabetes.
AB  - The effects of vasodepressor (acetylcholine and bradykinin) and pressor
      [electrical stimulation of the spinal sympathetic outflow, norepinephrine and
      endothelin-1 (ET-1)] stimuli were determined in rats with 2- and 5-week untreated
      streptozotocin-induced diabetes (blood glucose 400 and >500 mg/dl, respectively).
      In pentobarbital-anesthetized animals, the hypotensive response to an intravenous
      dose of acetylcholine or bradykinin was unaffected in animals treated for 2 weeks
      with streptozotocin but was significantly reduced (22% and 48%, respectively)
      after 5 weeks. However, the pressor responses to ET-1 were significantly
      decreased in animals that had been given streptozotocin 2 (38%) and 5 (45%) weeks
      previously. In contrast, the vasoconstrictor effects of electrical stimulation of
      the spinal cord outflow and norepinephrine were significantly inhibited (47% and
      30%, respectively) at 5 weeks, but not at 2 weeks, after streptozotocin
      administration. These results indicate that, in untreated streptozotocin
      diabetes, a substantial impairment of vascular reactivity to ET-1 appears more
      rapidly than inhibition of the pressor responses to endogenous and exogenous
      norepinephrine or to vasodilator substances that require integrity of vascular
      endothelial cell function to produce their normal effects.

PMID- 9595422
TI  - Endothelin-B receptor-mediated suppression of endothelial apoptosis.
AB  - Endothelin (ET)-1 is an endothelium-derived vasoconstrictor as well as a mitogen.
      We have recently described a novel role of ET-1 as a survival factor for rat
      endothelial cells from serum deprivation-induced apoptosis. The present study was
      designed to determine which receptor subtype (ETA or ETB) is responsible for and
      what intracellular mediators are involved in endothelial apoptosis. Apoptotic
      cell death was evaluated by nucleosomal ladders on agarose gel electrophoresis
      and immunohistochemical study using anti-single-stranded DNA antiserum. ET-1 and
      an ETB receptor agonist suppressed endothelial apoptosis, whose effects were
      abrogated by an ETB receptor antagonist but not by an ETA receptor antagonist.
      Addition of an ETB receptor antagonist or nonselective ETA/B receptor
      antagonists, but not an ETA receptor antagonist, enhanced the apoptotic events
      caused by serum deprivation, suggesting an autocrine/paracrine role of endogenous
      ET-1 in protecting against endothelial apoptosis. The effect of ET-1 in
      suppressing apoptosis was unaffected by any of the following reagents: a
      phospholipase C inhibitor (U73122), a tyrosine kinase inhibitor (ST638), an MEK
      inhibitor (PD98059), a phosphatidylinositol-3 kinase inhibitors (wortmannin,
      LY294002). Taken together, these results confirm a role for ET-1 as an
      autocrine/paracrine survival factor for rat endothelial cells, in which neither
      phospholipase C, tyrosine kinase, MAP kinase, nor phosphatidylinositol-3 kinase
      is involved in mediating the antiapoptotic effect of ET-1.

PMID- 9595423
TI  - Expression of parathyroid hormone/parathyroid hormone-related protein receptor in
      vascular endothelial cells.
AB  - The parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor has been
      reported to be expressed in many tissues, including vascular smooth-muscle cells
      (VSMCs), but it has not been identified in vascular endothelial cells. To
      determine whether vascular endothelial cells can express the PTH/PTHrP receptor,
      its gene expression was examined in simian virus 40-transformed rat lung vascular
      endothelial cells (TRLECs) by the reverse-transcription polymerase chain reaction
      (RT-PCR). Results in TRLEC, with rat VSMCs and kidney as controls, showed
      identical 741-bp products. Furthermore, incubation with PTHrP[1-34] reduced the
      thrombin-stimulated endothelin-1 (ET-1) expression in TRLECs. Our results
      demonstrate that vascular endothelial cells can express the PTH/PTHrP receptor
      and therefore are also a target tissue for PTHrP.

PMID- 9595424
TI  - The Endothelin-A antagonist LU 135 252 supresses ischemic ventricular
      extrasystoles and fibrillation in pigs and prevents hypoxic cellular decoupling.
AB  - The endothelin-A (ETA) antagonist LU 135 252 (1 mg/kg, n = 10) or saline
      (control, n = 10) was injected i.v. into anesthetized pigs 15 min before
      occlusion of the last third of the left anterior descending coronary artery (LAD)
      for up to 90 min. Then, or when ventricular fibrillation occurred, the ischemic
      mass was determined and amounted to about 13% of ventricular mass in all groups.
      Heart rate, QT interval, blood pressure, and the left ventricular contractility
      parameter LV dp/dtmax were not altered by LU in the 15 min pretreatment period.
      The lower dose of the ETA antagonist had only marginal antiarrhythmic effects. At
      the 3 mg/kg dose, LU prolonged the time of regular sinus rhythm within the first
      20 min of ischemia by 50% (mean +/- SEM: 12 +/- 2 min in control vs. 18 +/- 1
      after LU; p < 0.05) and reduced the number of ventricular extrasystoles by 87%
      (54 +/- 18 vs. 7 +/- 3; p < 0.05). The total incidence of ventricular
      fibrillation (VF) (80% vs. 50%; p = 0.17) and also the incidence of late VF
      (ischemia > 20 min) was reduced by 3 mg/kg LU (78% vs. 38%; p = 0.12). In vitro,
      LU (10(-6) mol/L) prevented the hypoxia-induced (N2 gassing) impairment of
      intercellular coupling, measured as the delay between a direct stimulus and a
      distal action potential in guinea pig papillary muscles.

PMID- 9595425
TI  - Plasma- and cerebrospinal fluid-immunoreactive endothelin-1: effects of
      nonpeptide endothelin receptor antagonists with diverse affinity profiles for
      endothelin-A and endothelin-B receptors.
AB  - Some endothelin (ET) receptor antagonists have been reported to elevate plasma
      immunoreactive endothelin-1 (irET-1). However, there is no information regarding
      the effects of ET receptor antagonists on cerebrospinal fluid (CSF) levels. To
      better understand the regulation of circulating and CSF ET-1, the effects of
      several nonpeptide antagonists with high, intermediate, or low affinity at the
      ETB receptor, as well as the potent ETB selective agonist sarafotoxin 6c (S6c),
      were characterized and compared. The effects of SB209670 (Ki ETA = 0.2 nM; Ki ETB
      = 12 nM), SB217242 (Ki ETA = 1.1 nM; Ki ETB = 111 nM), SB234551 (Ki ETA = 0.1 nM;
      Ki ETB = 500 nM), SB247083 (Ki ETA = 0.4 nM; Ki ETB = 467 nM), and S6c (Ki ETA =
      950 nM; Ki ETB = 1 nM) on plasma irET-1 were determined by ELISA in the
      anesthetized dog after i.v. administration. Systemic administration of equivalent
      doses of the nonpeptide ET receptor antagonists produced dose-related elevations
      in plasma irET-1 which were correlated (p = 0.019) with affinity at the ETB
      receptor. There was no significant correlation with affinity at the ETA receptor.
      In addition, the plasma irET-1 and ET antagonist concentrations were linearly
      correlated (r = 0.98) throughout the time course after antagonist administration.
      There was no evidence of densensitization after three bolus administrations
      performed at 2-h intervals (SB209670, 1 and 3 mg/kg i.v.). Elevations in plasma
      irET-1 (four- to fivefold) were also observed after systemic administration of
      S6c (1 nmol/kg i.v.). The administration of L-NAME (200 micrograms/kg/min for 30
      min), an inhibitor of nitric oxide (NO) synthase, increased blood pressure (33%)
      but did not alter plasma irET-1. In contrast, systemic administration of the ET
      receptor antagonists had little or no effect on the on irET-1 in the CSF.
      However, intracerebroventricular (i.c.v.) administration of SB209670 produced a
      dose-related (3-100 micrograms) increase in cisternal CSF levels of irET-1
      without altering plasma irET-1. Systemic administration of ETB receptor
      antagonists and agonists rapidly increased plasma irET-1. These ETB receptor
      antagonist effects correlate linearly with affinity at the cloned human ETB
      receptor, do not exhibit desensitization, and do not appear to reflect inhibition
      of ETB-mediated NO production. The endothelial ETB receptor may represent a high
      capacity storage/clearance site for circulating ET-1. ET receptor antagonists may
      also act extravascularly/abluminally to increase irET-1 in the CNS.

PMID- 9595426
TI  - Regulation of endothelin-B receptor mRNA expression in human endothelial cells by
      cytokines and growth factors.
AB  - The regulation of endothelin-B receptor (ETB) mRNA expression in human
      endothelial cells (ECs) by cytokines and growth factors may play an important
      role in the response of the endothelium to inflammatory and angiogenic stimuli.
      Using quantitative RT-PCR, we studied ETB expression in human umbilical vein ECs
      (HUVECs) grown in culture on either plastic or fibrin matrix for 24 h in the
      presence or absence of tumor necrosis factor-alpha (TNF-alpha, 100 U/ml) or basic
      fibroblast growth factor (bFGF, 30 ng/ml). In addition, the effect of the nitric
      oxide (NO) donor S-nitrosyl-acetylpenicillamine (SNAP, 0.4 mM) was examined
      directly on ETB expression or on the response to bFGF. Under control conditions,
      ETB mRNA was detected after 35 cycles of amplification as a band of the expected
      size (553 bp). In the absence of fibrin matrix, ETB was downregulated by bFGF and
      TNF-alpha and could barely be detected by PCR. Southern analysis of the RT-PCR
      products after 25 cycles revealed that bFGF reduced ETB mRNA expression by 2.7 +/
      0.4-fold (p < 0.01) and TNF-alpha tended to reduce its expression by 1.8 +/- 0.9
      fold of control, although this did not reach statistical significance (p < 0.20).
      In contrast, on fibrin matrix both bFGF and TNF-alpha increased ETB mRNA
      expression by 25 +/- 9-fold (p < 0.05) and 68 +/- 19-fold (p < 0.05) of control,
      respectively, suggesting a role for ETB in the vascular tube formation that
      occurs under these conditions. Pharmacologic addition of NO mimicked the effect
      of fibrin, converting the response to bFGF from down- to upregulation of ETB,
      raising the possibility that NO acts as a molecular switch modulating the
      response to angiogenic factors.

PMID- 9595427
TI  - Endothelin-B receptor-dependent modulation of the pressor and prostacyclin
      releasing properties of dynamically converted big endothelin-1 in the
      anesthetized rabbit.
AB  - Big endothelin-1 (ET-1) injected systemically in vivo induces a long-lasting
      pressor response, in contrast to its active metabolite ET-1, which alters in a
      biphasic fashion the mean arterial pressure (MAP) of the anesthetized rabbit. In
      this study we investigated the effect of selective ETA or ETB receptor blockade
      on the pressor response and increase in plasma prostacyclin (PGI2) levels
      (determined by RIA) induced by big ET-1 in the anesthetized rabbit. Pretreatment
      (5 min) of the rabbit with the ETB receptor antagonist BQ-788 (0.25 mg/kg)
      potentiated the ET-1 (1 nmol/kg) and, interestingly, big ET-1 (0.5 nmol/kg)
      induced pressor responses. The selective ETA receptor antagonist BQ-123 (1 mg/kg)
      significantly reduced the big ET-1 (0.5 and 3 nmol/kg) pressor responses. Big ET
      1 (3 nmol/kg) injected i.v. induced an increase in plasma PGI2 levels in contrast
      to intra-arterial (i.a.) administration. This increase was prevented by BQ-123 (1
      mg/kg) but not by BQ-788 (0.25 nmol/kg). Furthermore, in the presence of BQ-788,
      i.a. administration of big ET-1 (3 nmol/kg) induced a significant release of
      PGI2. These results show that vasodilator ETB receptors may be activated after
      conversion of big ET-1 to its active metabolite. Furthermore, after pulmonary
      conversion of big ET-1, ETA receptors may be responsible for the release of
      vasodilator and anti-aggregatory prostacyclin, which modulates the big ET-1
      induced responses in the rabbit.

PMID- 9595428
TI  - Effects of human plasma proteins on endothelin binding and function.
AB  - We have previously shown that the endothelin (ET) isoforms ET-1 and ET-3 and ET
      receptor antagonists exhibit a high degree (> 98%) of binding to plasma proteins,
      especially serum albumin. This study examines the effects of human plasma
      proteins on ET-1 binding and ET-1 stimulated biologic responses. When ET-1
      binding to rat pituitary MMQ cells was examined, human serum albumin (HSA)
      inhibited ET-1 binding in a concentration-dependent manner, with 92% inhibition
      observed at 5% (w/v) HSA. A similar observation was made when human plasma was
      tested. Surprisingly, addition of human plasma (0-100%) or HSA (0-5%) did not
      have a significant effect on ET-1-stimulated phosphatidylinositol (PI) hydrolysis
      in these cells. In human pericardial smooth-muscle cells, HSA again exhibited
      profound inhibitory effects on ET-1 binding; 5% HSA inhibited ET-1 binding by
      84%. However, ET-1-stimulated arachidonic acid release in these cells was not
      significantly affected by HSA (0-5%). Addition of increasing concentrations of
      human plasma incrementally decreased the potency of PD-156707, and ETA-selective
      antagonist, on inhibiting ET-1-stimulated PI hydrolysis in the MMQ cells. These
      results suggest that, although ET-1 binding to the receptor is inhibited by human
      plasma proteins, especially HSA, ET-1-induced signal transduction is not
      significantly affected. Furthermore, plasma proteins decrease the potency of an
      ET receptor antagonist in inhibiting ET-1-stimulated biologic responses. This
      study may help to explain the discrepancy between in vitro and in vivo potencies
      of ET receptor antagonists.

PMID- 9595429
TI  - Enhancement of pulmonary artery contraction induced by endothelin-B receptor
      antagonism.
AB  - We previously reported that endothelin (ET)A and ETB receptors are involved in ET
      1-induced contraction in isolated rabbit pulmonary artery and human bronchus.
      However, the activity of an ETA/ETB dual antagonist was lower than expected in
      these tissues. In such ETA/ETB receptor composite-type tissues, low doses of the
      ETB antagonist BQ-788 shifted the concentration-contraction curve for ET-1
      slightly to the left, implying potentiation of contraction. Therefore, we
      investigated the potentiation of contraction by ETB antagonism in isolated rabbit
      pulmonary artery. In endothelium-denuded artery segments, ET-1 (10(-10) M)
      elicited sustained, almost half-maximal contraction. BQ-123 up to 10(-6) M did
      not affect contractile tone in ET-1-precontracted artery segments. In contrast,
      the ETB-selective antagonist BQ-788 (10(-8) M to 10(-7) M) enhanced contraction
      in ET-1-precontracted artery. In addition, in endothelium-intact artery samples,
      BQ-788 enhanced contraction to the same extent as in endothelium-denuded artery.
      In the presence of 10(-6) M BQ-123, BQ-788 failed to enhance contraction, and
      concentrations > 10(-7) M elicited only relaxation. The present results suggest
      that blockade of ETB receptors increases contractile tone through an endothelium
      independent mechanism, possibly by inhibition of ETB-mediated regional clearance
      of ET-1 and/or of an ETB-mediated inhibitory mechanism, in rabbit pulmonary
      artery. This action may explain the decreased potency of ETA/ETB dual antagonists
      in ETA/ETB composite-type tissue responses.

PMID- 9595430
TI  - Atypical antagonism observed with BQ-123 in human saphenous vein.
AB  - At present, endothelin (ET) receptor classification remains controversial. We
      investigated the presence of atypical ETA receptors in human saphenous veins
      (SV). Human SV was obtained from 24 patients undergoing coronary artery bypass
      grafting. Vessels were set up in organ baths, stretched to a tension of 6 g, and
      left to relax before being challenged with 90 mM KCl. After KCl challenge,
      tissues were incubated with 2.8 microM indomethacin and 100 microM L-NMMA for 30
      min followed by 30 min in the presence of antagonist before a concentration
      response curve to ET-1 or sarafotoxin 6b (S6b) (10(-10)-10(-7) M) was
      constructed. In endothelium-intact vessels, incubated with indomethacin and L
      NMMA, BQ-123 (1 microM) caused nonparallel shifts, with lower concentrations of
      ET-1 being antagonized more than higher concentrations. This antagonism with BQ
      123 was unaffected by BQ-788 (0.1 microM; n = 6) or by desensitization of ETB
      receptors with S6c (0.1 microM; n = 8). Blocking the Ca2+ channels with
      nifedipine (1 microM; n = 5) did not affect the antagonism, nor did denuding the
      endothelium or leaving the endothelium intact (n = 5). When S6b was used as an
      agonist, BQ-123 (0.3-3 microM) caused concentration-dependent biphasic shifts,
      with low concentrations of S6b not being antagonized. In conclusion, the
      antagonism observed with BQ-123 is not due to the action of ET-1 at ETB
      receptors, changes in Ca2+ handling, or endothelium. This unusual action of BQ
      123 suggests subtypes of the ETA receptor.

PMID- 9595431
TI  - Distinct endothelin-B receptors mediate the effects of sarafotoxin S6c and
      IRL1620 in the ileum.
AB  - In the guinea pig ileum, both sarafotoxin S6c (S6c) and IRL1620 induced a
      biphasic effect (relaxation and contraction). S6c induced strong tachyphylaxis of
      both components of the response, but IRL1620 induced tachyphylaxis mainly of the
      contractile component. Whereas the tissues rendered tachyphylactic to S6c did not
      respond to IRL1620, a normal biphasic response to S6c was observed in the tissues
      rendered tachyphylactic to IRL1620. In the presence of IRL1620, S6c could induce
      its biphasic effect, whereas in the presence of S6c, IRL1620 was ineffective. BQ
      123, a specific ETA antagonist, did not affect the biphasic response induced by
      either agonist. PD145065, a potent ETA/ETB antagonist, was a competitive and a
      noncompetitive antagonist, respectively, of the contractile components of IRL1620
      and S6c. RES-701-1, a specific ETB1 antagonist, inhibited both components of the
      response induced by IRL1620. However, it inhibited mainly the relaxant component
      induced by low doses of S6c. Apamin had different effects on endothelin-1 (ET-1),
      S6c, and IRL1620. Our results suggest that there are at least two distinct
      populations of ETB receptors mediating the biphasic response: the ETB1 receptor,
      sensitive to RES-701-1 and PD145065, and the ETB2 receptor, less sensitive to RES
      701-1 and PD145065.

PMID- 9595432
TI  - Endothelin-1 signaling is altered in cardiac cells from deoxycorticosterone
      acetate-salt hypertensive rats.
AB  - The cardiac cellular effects of endothelin-1 (ET-1) on intracellular free Ca2+
      concentration ([Ca2+]i) were investigated in deoxycorticosterone acetate (DOCA)
      salt rats with severe cardiac hypertrophy. [Ca2+]i was measured by fura-2
      methodology in ventricular cardiomyocytes and fibroblasts of DOCA-salt
      hypertensive and control unilaterally nephrectomized rats (Uni-Nx). Blood
      pressure and heart weight were increased (p < 0.01) in DOCA-salt rats compared to
      control rats. ET-1 (10(-12)-10(-6) M) increased [Ca2+]i in a dose-dependent
      manner in both cell types from control and hypertensive rats. However, ET-1
      induced [Ca2+]i responses were significantly attenuated (p < 0.01) in
      cardiomyocytes and fibroblasts of DOCA-salt rats. Sarafotoxin S6c (S6c) increased
      [Ca2+]i in fibroblasts but not in cardiomyocytes. In conclusion, ET-1 dose
      dependently increased [Ca2+]i in cardiomyocytes (primarily via ETA receptors) and
      fibroblasts (via ETA and ETB receptors). Cardiac cell ET-1 signaling pathways are
      blunted in DOCA-salt hypertensive rats. ET-1 may not play a critical role in the
      pathophysiology of the severe concentric cardiac hypertrophy present in DOCA-salt
      hypertensive rats.

PMID- 9595433
TI  - Endothelin-1 stimulates DNA synthesis of vascular smooth-muscle cells through
      transactivation of epidermal growth factor receptor.
AB  - To elucidate the molecular mechanism of the mitogenic effect of endothelin-1 (ET
      1) on vascular smooth-muscle cells (VSMCs), we studied the effect of AG1478, a
      novel epidermal growth factor receptor (EGFR) kinase inhibitor, on p42/44 mitogen
      activated protein (MAP) kinase activation, c-Fos expression, and DNA synthesis
      stimulated by ET-1. AG1478 dose-dependently (2.5 x 10(-8) M-2.5 x 10(-7) M)
      inhibited ET-1-induced MAP kinase activation. The ET-1-induced c-Fos protein
      expression was inhibited by AG1478 (2.5 x 10(-7) M). AG1478 also dose-dependently
      inhibited ET-1-stimulated [3H]thymidine incorporation. These data suggest that ET
      1 induces MAP kinase activation, c-Fos expression, and promotes proliferation of
      VSMCs via transactivation of EGFR.

PMID- 9595434
TI  - Endothelin and isoproterenol counter-regulate cAMP and mitogen-activated protein
      kinases.
AB  - Mitogen-activated protein kinases (MAPK) and cAMP are important components of the
      intracellular signaling pathways. We studied the effects of endothelin-1 (ET-1)
      and isoproterenol (ISO) on the intracellular cAMP level in human pericardial
      smooth-muscle cells and investigated how these two ligands regulate the activity
      of MAPK (p42/p44 MAPK). ET-1 or ET-3 alone did not exhibit any effect on the cAMP
      level in these cells. In contrast, ISO at 10 microM caused a 12-fold increase in
      the accumulation of cAMP (370 +/- 70 pmol/ml vs. 31 +/- 5 pmol/ml). Addition of
      ET-1 attenuated ISO-stimulated cAMP accumulation by 50% in a dose-dependent
      manner, with an IC50 of 0.12 nM. ET-3 was 100-fold less potent (IC50 = 15 nM).
      The attenuating effect of ET-1 was completely blocked by 1 microM FR139317,
      suggesting that the effect is primarily mediated by the ETA receptor. In serum
      deprived cells, the basal MAPK activity was low (0.07 +/- 0.01 nmoles Pi/mg/min).
      Addition of 10 nM ET-1 stimulated MAPK 15-fold within 5 min at 37 degrees C (1.08
      +/- 0.02 nmoles Pi/mg/min). ISO alone (10 microM) had no significant effect on
      MAPK. However, ISO markedly attenuated ET-1-stimulated MAPK activity; a
      approximately 50% decrease in MAPK activity was observed in the presence of 10
      microM ISO. Similar results were obtained when forskolin was tested. The effects
      of ISO and forskolin on attenuating ET-1-stimulated MAPK activity could be
      reversed by treating cells with H89, an inhibitor of protein kinase A. These
      results show that ET-1 partially attenuated the accumulation of cAMP induced by
      ISO, and that ISO attenuated the MAPK activity induced by ET-1, possibly via
      activation of protein kinase A. This study suggests that counter-regulation among
      various ligands and cross-talk among different signaling pathways may be required
      to modulate biologic functions in a living cell.

PMID- 9595435
TI  - Assessment of endothelin receptor subtype-mediated increases of [Ca2+]i in
      distinct rat cell types using fluorimetric imaging.
AB  - Activation of endothelin (ET) receptor subtypes by various agonists causes an
      increase in [Ca2+]i in different cell types. This effect can be readily monitored
      in a 96-well plate format by detecting 1-s fluorescence changes of cell-permeant,
      Ca(2+)-sensitive dyes (e.g., Calcium Green-1 AM) using a fluorimetric imaging
      plate reader. This device was used to assess the ET receptor subtypes in primary
      cultures of rat mixed neocortical neuronal/glial cells and aortic smooth-muscle
      cells. Pharmacologic experiments with several ET receptor agonists and
      antagonists indicated that the ETA receptor subtype was functionally responsive
      in the smooth-muscle cells and that the ETB receptor subtype had a similar role
      in the mixed neuronal/glial cells.

PMID- 9595436
TI  - Differential regulation of endothelin-1 action by insulin and vanadate in
      vascular smooth muscle.
AB  - The effects of insulin (10 nM) and sodium orthovanadate (SOV, 25 microM)
      pretreatment for 24 h on endothelin-1 (ET-1) and IRL-1620 (ETB agonist)-evoked
      increases in intra-cellular free calcium levels [Ca2+]i were determined by fura-2
      fluorescence methodology using cultured rat aortic smooth-muscle cells (ASMCs).
      Whereas insulin preincubation led to an increase (p < 0.05) in [Ca2+]i responses
      to ET-1, SOV enhanced [Ca2+]i responses to both ET-1 (p < 0.05) and IRL-1620 (p <
      0.01). Saturation binding studies revealed that insulin pretreatment led to a 2.2
      fold (p < 0.01) increase in [125I]ET-1 binding sites, and SOV pretreatment led to
      a 2.4-fold (p < 0.01) and 6.6-fold (p < 0.01) increase in the maximal number of
      binding sites labeled by [125I]ET-1 and [125I]IRL-1620, respectively. Northern
      blot analysis revealed that insulin upregulated only ETA mRNA levels, and SOV
      enhanced both ETA and ETB mRNA levels. Pretreatment with the tyrosine kinase
      inhibitor genistein abolished these effects. These data suggest that insulin
      pretreatment of ASMCs selectively upregulates ETA receptor expression and ETA
      mediated [Ca2+]i, signaling, and SOV upregulates both ETA and ETB receptor
      expression and exaggerates [Ca2+]i responses mediated by both ETA and ETB in rat
      ASMCs.

PMID- 9595437
TI  - Nuclear Ca2+ signaling to endothelin-1 in rat aortic smooth-muscle cells.
AB  - Vascular smooth-muscle cells (VSMCs) isolated from genetically hypertensive
      animals show increased intracellular free calcium levels ([Ca2+]i) in response to
      endothelin-1 (ET-1). The differences in time course and distribution of Ca2+
      increase after addition of ET-1 within the VSMCs are unknown. Therefore, ET-1
      evoked changes in fluo-3 fluorescence were determined using a confocal laser
      scanning microscope in primary cultures of aortic smooth-muscle cells (ASMCs)
      from 12-week-old male Sprague-Dawley (SD) rats, Wistar-Kyoto (WKY) rats, and
      spontaneously hypertensive rats (SHR). Syto-11 staining enabled the assessment of
      intracellular free [Ca2+]i changes in the cytosolic ([Ca2+]c), perinuclear
      ([Ca2+]p), and nuclear ([Ca2+]n) regions. In the basal state, [Ca2+] was evenly
      distributed throughout the rat ASMCs. There were no significant differences in
      basal fluorescence values among the three strains. ET-1 evoked a concentration
      dependent increase in fluo-3 intensity. The peak [Ca2+]i rise to ET-1 was much
      more rapid in ASMCs from SHR and WKY strains. The changes in [Ca2+]n were greater
      than in [Ca2+]c. Pretreatment of rat ASMCs with BQ-123 (an ETA antagonist) and BQ
      788 (an ETB antagonist) abolished the rapid peak rise and the slow sustained
      elevation in [Ca2+]i, respectively. The nonselective antagonist bosentan
      attenuated both phases of the ET-1 response in all three strains. The ETB
      selective agonist IRL 1620 evoked a significant elevation in [Ca2+]n values at 2
      min in the ASMCs of SHR. These data suggest that ETA activation is linked to
      initial rapid increases in [Ca2+]c and [Ca2+]n, whereas ETB activation promotes
      slow [Ca2+]n signaling, particularly in ASMCs of SHR.

PMID- 9595438
TI  - Subtype-specific endothelin-A and endothelin-B receptor desensitization
      correlates with differential receptor phosphorylation.
AB  - In the rat cardiovascular system endothelin-1 (ET-1) elicits prolonged
      physiologic responses mediated by the ETA receptor, whereas the effects mediated
      by the ETB receptor are transient. The molecular mechanisms for the subtype
      specific responses are not yet clear. However, post-translational modifications
      such as phosphorylation and palmitoylation may play an important role. In Sf9
      cells overexpressing the human ETA and ETB receptors, both subtypes are
      palmitoylated. However, only the ETB but not the ETA receptor is phosphorylated
      in a ligand-dependent manner. Because phosphorylation is believed to play an
      important role in ligand-dependent receptor inactivation, we analyzed whether the
      differential phosphorylation of the ETA and ETB receptors reflects a differential
      mechanism of receptor inactivation. Using a modified inositol phosphate
      accumulation assay, we analyzed CHO cells that expressed the ETA or ETB receptor.
      The ETB receptor was deactivated almost completely within 5 min after agonist
      stimulation, whereas stimulation of the ETA receptor resulted in sustained
      activation, i.e., > 90% of the initial activity was maintained after 5 min of
      ligand stimulation and > 30% after 20 min. A strong correlation was observed
      between the time course of ETA receptor inactivation and ETA receptor
      internalization. The endogenous ETA receptor in Rat-1 cells produced a prolonged
      stimulation of phospholipase C similar to that seen in CHO cells. Therefore, the
      sustained signaling activity of the ETA receptor is not a property only of
      recombinant cell lines. Together, our data suggest rapid ETB receptor
      inactivation due to phosphorylation and delayed ETA receptor inactivation by
      internalization. These mechanisms adequately reflect the differential response
      patterns of the ET receptors under physiologic conditions.

PMID- 9595439
TI  - Distribution of endothelin-B receptor-like immunoreactivity in rat brain, kidney,
      and pancreas.
AB  - We investigated the distribution of endothelin B (ETB) receptor-like
      immunoreactivity in rat brain, kidney, and pancreas, using an antiserum against
      amino acid residues 425-439 of the rat ETB receptor modified by the multiple
      antigen peptide complex system. In the brain, immunoreactive fibers were observed
      mainly in the hypothalamus and diagonal band of Broca. Densely arranged
      immunoreactive fibers were observed in the organum vasculosum of the lamina
      terminalis and the median eminence. In these areas, the immunoreactive fibers
      corresponded to luteinizing hormone-releasing hormone-immunoreactive fibers. In
      the kidney, intense ETB receptor-like immunoreactivity was seen in structures
      that were presumably proximal tubules. In other segments of renal tubules and
      collecting ducts, immunoreactive puncta were scattered. In the glomerulus, a few
      immunoreactive puncta were seen on the capillaries. In the pancreas, ETB receptor
      like immunoreactivity was seen in the acinar cells and islets of Langerhans. By
      analysis of double staining in the same section, B and D cells showed intense
      immunoreactivity, whereas A cells showed only weak immunoreactivity. These
      results suggest that the ETB receptor or its subtype is localized in specific
      cell types in the organs investigated. In these cells, ET(s) may modulate the
      function of each cell type via this type of receptor.

PMID- 9595440
TI  - Immunoreactive endothelin-1 and its receptors in human adrenal tissues.
AB  - To elucidate the pathophysiologic significance of endothelin-1 (ET-1) in adrenal
      and the mechanism for reduced responsiveness to exogenous ET-1 in aldosterone
      producing adenoma (APA), we have investigated ET-1 receptors by radioligand
      binding assay (RBA) in human normal adrenal (NA), APA, idiopathic
      hyperaldosteronism (IHA), and pheochromocytoma (PHEO), immunoreactive (ir-) ET-1
      content in NA, APA and PHEO by radioimmunoassay (RIA), and immunohistochemical
      staining of ET-1 with the peroxidase-anti-peroxidase (PAP) method in NA, APA, and
      PHEO. A single class of high-affinity binding sites for ET-1 was found in human
      NA and tumor tissues. Dissociation constant (Kd) values of ET-1 receptors were
      similar in NA, APA, and IHA, but maximal binding capacity (Bmax) of ET-1
      receptors was lower in APA than in NA and IHA. Both Kd and Bmax in PHEO were
      higher than those in NA, APA, and IHA. Ir-ET-1 content in tumors of APA and PHEO
      were higher than in NA. Immunohistochemical staining was more intense in the
      tumor cells of APA and PHEO than in NA. These results suggest that the reduced
      response to exogenous ET-1 in APA could be related to downregulation of ET-1
      receptors in the tumor. Increased ET-1 content and receptors may lead to
      hypersecretion of catecholamine in PHEO. ET-1 produced in normal and tumor
      adrenal tissues may regulate aldosterone and catecholamine secretion from
      adrenals in a paracrine/autocrine fashion.

PMID- 9595441
TI  - Histochemical studies on endothelin and the endothelin-A receptor in the
      hypothalamus.
AB  - By use of a rabbit polyclonal antibody specific to the endothelin-A (ETA)
      receptor, we analyzed the distribution of neurons containing ETA receptors in rat
      brain. Almost all A1-A7 noradrenergic neurons, A8-A16 and retinal amacrine (A17)
      dopaminergic neurons (except the A15 group), and C3 adrenergic neurons contained
      ETA receptors. In addition, hypothalamic magnocellular (noncatecholaminergic)
      neurons also showed immunoreactivity to ETA receptors, whereas the staining
      intensity was low. These observations were confirmed by analyzing the expression
      of c-fos in the hypothalamus after central injection of ET isopeptides. We also
      examined immunohistochemically the distribution of big ETs and mature ETs in the
      hypothalamus. The paraventricular and supraoptic magnocellular neurons in the
      hypothalamus were immunopositive for big ET-1 and mature ET-1. However, their
      nerve fibers were immunostained only with antibody to big ET-1. The observations
      on big ET-1 were altered by colchicine treatment. Considering all the evidence,
      mature ET-1 may regulate neurotransmission in the hypothalamic region, whereas
      big ET-1 is secreted from nerve terminals into the vessels as a neurohormone. It
      is also concluded that ET, one of the "brain-vascular peptides," has a close
      relationship with the catecholamine neuron system in the brain.

PMID- 9595442
TI  - Influence of respiratory tract viral infection on endothelin-1-induced modulation
      of cholinergic nerve-mediated contractions in murine airway smooth muscle.
AB  - The effects of endothelin-1 (ET-1) and sarafotoxin S6c (S6c) on cholinergic
      contractions elicited by electrical field stimulation (EFS) were examined in
      mouse tracheal preparations from healthy animals and from animals infected with
      parainfluenza-1 (P-1) virus. S6c (an ETB-selective agonist) and ET-1 caused
      marked ETA and/or ETB receptor-mediated potentiation of EFS-induced contraction
      in tracheal tissue from both groups. Despite the fact that such infection is
      known to markedly alter ET receptor density and function in mouse tracheal smooth
      muscle, no evidence for modulated neuronal ET receptor function was obtained. The
      reason for this differential sensitivity of smooth muscle and neuronal ET
      receptors to P-1 infection is unknown.

PMID- 9595443
TI  - Immunocytochemical detection of endothelin receptors in rat cultured airway
      nerves.
AB  - Endothelin-1 (ET-1) has been shown to potentiate cholinergic neurotransmission in
      human bronchus as well as in airways from a variety of animal species, suggesting
      that ET receptors exist prejunctionally on airway cholinergic nerves. We have
      successfully isolated and maintained rat tracheal para-sympathetic neurons in
      culture. Most cultured cells were associated with specific fluorescence for the
      nerve cell marker protein gene product 9.5 (PGP 9.5). These cultures contained a
      high proportion of parasympathetic neurons. Importantly, specific
      immunofluorescent antibodies for ETB receptors were colocalized with those for
      PGP 9.5. Therefore, for the first time, ETB receptors have been shown to exist on
      airway parasympathetic neurons in culture.

PMID- 9595445
TI  - Cysteine residues in the carboxyl terminal domain of the endothelin-B receptor
      are required for coupling with G-proteins.
AB  - We demonstrate that the human endothelin-B (ETB) receptor incorporates
      [3H]palmitic acid. Mutation of three putative palmitoylated cysteine residues
      (amino acids 402, 403 and 405) in the carboxyl terminus into serine residues
      (C2/3/5S) completely prevented palmitoylation of ETB. When expressed in CHO
      cells, C2/3/5S was localized on the cell surface, retained high affinity for ET-1
      and ET-3, and was rapidly internalized when bound to the ligand. However, unlike
      the wild-type ETB, C2/3/5S transmitted neither an inhibitory effect on adenylate
      cyclase nor a stimulatory effect on phospholipase C, indicating a critical role
      of palmitoylation in the coupling with G-proteins, regardless of the G-protein
      subtype. Truncation of the carboxyl terminus, including all or a part of the
      three cysteine residues, gave palmitoylation-negative and -positive deletion
      mutants, delta 402 and delta 403. Despite the absence of the cytoplasmic tail,
      both delta 402 and delta 403 showed essentially the same features as C2/3/5S,
      except that delta 403 did transmit a stimulatory effect on phospholipase C via a
      pertussis toxin-insensitive G-protein, most likely a member(s) of the Gq family.
      These results indicated a differential requirement for the carboxyl terminus
      downstream from the palmitoylation site in the coupling with G-protein subtypes,
      i.e., it is required for the coupling with Gi but not for that with Gq.

PMID- 9595444
TI  - Effects of follicle-stimulating hormone on endothelin receptors in cultured rat
      ovarian granulosa cells.
AB  - Two subtypes of the endothelin (ET) receptor (ETA and ETB) were studied in
      cultured ovarian granulosa cells. Immature 21-day-old female Wistar-Imamichi rats
      were implanted with diethylstilbestrol (DES) pellets for 5 days and granulosa
      cells were collected by repeated puncturing. Viable cells (2.5 or 5 x 10(5)) were
      cultured with 50--400 ng/ml of ovine NIH follicle-stimulating hormone (FSH) in
      the presence or absence of [125I-Tyr13]ET-1 (50 pM) in 1 ml McCoy's 5a medium for
      72 h. FSH gradually increased the [125I-Tyr13]ET-1 binding to granulosa cells,
      whereas FSH-untreated granulosa cells had no significant changes. The dose of 200
      ng/ml of FSH was most effective for [125I-Tyr13]ET-1 binding for 48-h culture,
      thereafter revealing a plateau. After 48 h of culture with 200 ng/ml of FSH,
      granulosa cells were further incubated with [125I-Tyr13]ET-1 (10 pM-1 nM) and/or
      [125I]IRL1620, the selective ETB receptor agonist (10 pM-1 nM) for 2 h for
      equilibrium study, and then the dissociation constant and the maximal binding
      capacity between receptors and ligands were determined by saturation curve and
      Scatchard plot analysis. ETA + ETB, ETB, and ETA (sites/cells) showed a 4.4-, 2.6
      , and 7.5-fold increase, respectively. As for steroidogenesis, ET-1 (100 nM) or
      ET-3 (100 nM) suppressed FSH-induced progesterone and 17 beta-estradiol
      production. These results indicate that FSH upregulates both ETA and ETB
      receptors in DES-treated immature rat granulosa cells, with no significant
      differences between ET-1 and ET-3, and that ET-1 or ET-3 suppresses FSH-induced
      steroidogenesis. ETs may affect the granulosa cell function through the ETA and
      ETB receptors, and the increase in amount of ET binding does not reflect ET
      effects on granulosa cell function. The ET receptor plays an important role in
      the development of the ovary.

PMID- 9595446
TI  - Pathologic role of endothelin-1 in septic shock.
AB  - To elucidate the pathologic role of endothelin-1 (ET-1) in septic shock, we
      measured plasma ET-1 concentrations after bacterial lipopolysaccharide (LPS)
      administration in dogs and determined systemic, pulmonary, and renal hemodynamics
      and blood gas parameters with or without the nonselective ET receptor antagonist
      TAK-044. Plasma ET-1 concentrations increased significantly after LPS
      administration, which correlated positively with mean arterial pressure, mean
      pulmonary arterial pressure, pulmonary capillary wedge pressure, and central
      venous pressure. LPS infusion induced hypotension, metabolic acidosis, hypoxemia,
      and renal dysfunction. TAK-044 prevented LPS-induced metabolic acidosis,
      hypoxemia, and renal dysfunction, but not hypotension. These findings suggest
      that increased circulating ET-1 plays a compensatory role in the reversal of
      systemic vasodilatation in septic shock, but exerts deleterious effects on renal
      and pulmonary circulation.

PMID- 9595447
TI  - Chronic effects of a novel, orally active endothelin receptor antagonist, T-0201,
      in dogs with congestive heart failure.
AB  - Endothelin (ET)-1 increases in plasma during congestive heart failure (CHF). Some
      ET antagonists improve hemodynamics, suggesting its potential benefits in the
      treatment of CHF. We examined the acute and chronic effects of a new ET receptor
      antagonist, T-0201 (Tanabe Seiyaku Co. Ltd., Japan), in CHF. To confirm the in
      vivo effects of T-0201, we observed the inhibitory effects of T-0201 (1-100
      micrograms/kg) on the response of blood pressure to exogenously administered ET-1
      (0.75 nmol/kg) in conscious normal dogs. Pretreatment with T-0201 significantly
      inhibited the ET-1-induced initial hypotension that is mediated by ETB receptors,
      and attenuated the subsequent hypertension, which is primarily mediated by ETA
      receptors. Thus, T-0201 at a dose of 100 micrograms/kg not only works as a potent
      ETA antagonist but also shows antagonist activity for ETB receptors in dogs. To
      evaluate the chronic therapeutic effects of T-0201, we administered T-0201 (0.3
      mg/kg/day; n = 5) orally to dogs with CHF induced by rapid right ventricular
      pacing (22 days, 270 beats/min) for 15 days, beginning 8 days after pacing. T
      0201 significantly prevented the deterioration of cardiorenal function during the
      development of CHF, expressed as a decrease in cardiac pressure and an increase
      in cardiac and urine output. These results suggest that chronic antagonism of
      both ET receptors prevents the progressive exacerbation of CHF.

PMID- 9595448
TI  - PD156707: a potent antagonist of endothelin-1 in human diseased coronary arteries
      and vein grafts.
AB  - We have determined the ability of the endothelin A (ETA)-selective antagonist
      PD156707 to block constrictor ET-1 responses in blood vessels from the diseased
      human heart. ET-1 potently contracted nonatherosclerotic coronary arteries from
      patients with cardiomyopathy (pD2 = 7.96 +/- 0.15; n = 6), atherosclerotic
      coronary arteries from patients with ischemic heart disease (pD2 = 8.26 +/- 0.20;
      n = 4), and saphenous vein grafts that had developed "atherosclerotic" disease
      after coronary artery bypass (pD2 = 8.41 +/- 0.09; n = 6). PD156707 (100 nM)
      antagonized the vasoconstrictor response to ET-1 in each of the three
      preparations, with estimated pA2 values of 7.91 +/- 0.20, 8.05 +/- 0.14, and 8.07
      +/- 0.02, respectively. These data suggest that the upregulation of ETB receptors
      that has been reported in human atherosclerotic coronary arteries does not
      contribute significantly to the ET-1-mediated constrictor response in these
      vessels in vitro.

PMID- 9595449
TI  - LU 302 872 and its racemate (LU 224 332) show balanced endothelin-A/B receptor
      affinity, high oral activity, and inhibit human prostate tissue contractions.
AB  - LU 302 872 (racemate LU 224 332) is a new glycerinic acid derivative related to
      the selective ETA receptor antagonist LU 135 252. LU 302 872 exhibits high and
      balanced affinity to ETA and ETB receptors (Ki 2.2 and 5.8 nmol/L), whereas LU
      135 252 is ETA-selective (Ki 1.4 and 184 nmol/L). Two hours after oral treatment
      of rats with 10 mg/kg of LU 302 872 or of LU 135 252, the big ET-1-induced (20
      micrograms/kg i.v.) blood pressure increase is inhibited by 59 +/- 8% or 52 +/-
      2% (n = 6-8; p < 0.05 vs. control), whereas bosentan is without effect (-6 +/-
      7%; n = 6). In guinea pigs, 10 mg/kg p.o. of LU 302 872 inhibited the big ET-1
      (20 micrograms/kg i.v.)-induced bronchospasm (reduction in respiratory volume) by
      78 +/- 7% (n = 6; p < 0.05), whereas the ETA antagonist LU 135 252 was
      ineffective (0.2 +/- 37%; n = 6). Hence, a high oral effectiveness of the new
      ETA/B antagonist could be demonstrated in two species for both an ETA- or an ETB
      mediated response. In human prostate tissue (excised during cystectomy in bladder
      cancer patients), ET-1 and in most cases, the ETB agonist sarafotoxin 6c (S6c)
      caused contractions of similar magnitude but more sustained than that of
      norepinephrine (10(-6) mol/L). A high concentration (10(-5) mol/L) of the ETA
      antagonist LU 135 252 only moderately attenuated ET contractions. The ETA/B
      antagonist LU 302 872 or its racemate, LU 224 332, dose-dependently inhibited ET
      1-induced contractions. S6C dose-response curves, too, were shifted to the right
      or suppressed by the combined ETA/B antagonist (10(-6) mol/L LU 224 332). LU 302
      872 may be a suitable candidate for testing in benign prostate hyperplasia (BPH).

PMID- 9595450
TI  - Endothelin-A receptor antagonist combined with hydralazine improves survival and
      renal function in hypertensive rats.
AB  - To investigate the role of endothelin (ET) in severe hypertension, endothelial
      dysfunction hypercholesterolemic stroke-prone spontaneously hypertensive rats
      (SHRSP on a 5% cholesterol diet) were additionally fed with 1% NaCl and 0.023%
      nitro-L-arginine. Under these conditions, all untreated rats died within 30 days
      (median 17 days). A significant prolongation of survival (median 33 days) was
      achieved by combination treatment with hydralazine and the ETA receptor
      antagonist LU 135252. Monotherapy was less effective (LU 135252 18 days;
      hydralazine 28 days). Likewise, only treatment with the combination completely
      prevented the increase in systolic arterial pressure (SAP) seen in the control
      group during the first 10 days and delayed development of hypertension during the
      subsequent observation period. The superior efficacy of the combination was also
      reflected by improved kidney function. After 20 days of treatment, proteinuria
      had only increased to 1,272 +/- 135 mg/kg/day, a reduction of 45% compared to the
      untreated control group (2,300 +/- 346 mg/kg/day; p < 0.05). In this animal model
      of aggravated hypertension and endothelial dysfunction, the combination of LU
      135252 with hydralazine was superior compared to either monotherapy. Therefore,
      the combination of an ETA receptor antagonist with vasodilators may be a potent
      therapy to improve blood pressure, renal function, and survival in severe
      hypertension with concomitant metabolic disease.

PMID- 9595451
TI  - A study of an endothelin antagonist from a Chinese anti-snake venom medicinal
      herb.
AB  - Because it is well known that endothelin (ET) plays an important role in the
      pathogenesis of cardiovascular diseases, antagonists of ET for clinical use are
      very important. Because ET and some snake toxins have a homologous structure and
      similar biologic actions the effect of Chinese anti-snake venom herbal medicines
      on ET bioactivity was investigated both in vivo and in vitro. Hong Bei Si Chou
      [Cissus assamica (Laws.) Craib] is a herbal medicine used to treat snake bite in
      Guangxi province. It was found that all the different fractions of EtOH
      extraction, the EtOAc part of the EtOH extraction, and resverotrol (3,4'5
      trihydroxytransstilbene) isolated from the EtOAc part could antagonize ET both in
      vivo and in vitro. These three fractions transiently relaxed ET-contracted
      isolated rat aortic ring in a dose-dependent manner. They also antagonized the
      lethal effects of ET-1 in mice and inhibited blood pressure elevation induced by
      ET-1. The results have shown that it is possible to find ET antagonists in
      Chinese anti-snake venom medicinal herbs. In the future, our work should shed new
      light on the treatment of cardiovascular diseases in which ET is involved.

PMID- 9595452
TI  - Structure-activity analysis of C-terminal endothelin analogues.
AB  - Several synthetic endothelin (ET) analogues of the C-terminal ET hexapeptide
      (ET16-21) were analyzed by radio-receptor competition binding assays and biologic
      activity using both ETA and ETB receptor subtypes. In addition, we produced a
      hybridoma monoclonal antibody, anti-ET15-21, that appeared to crossreact with the
      entire ET molecule and was able to neutralize its biologic activity. Antibody
      binding was measured with competition enzyme-linked immunosorbent assays and a
      surface plasmon resonance-based biosensor (BIA technology). The ET16-21 moiety
      was modified with systematic replacement of each residue by alanine (Ala-scan).
      Whereas the C-terminal residues (Asp18, Ile20, and particularly Trp21) were very
      important for both receptor binding and immunologic activity, Ala substitution in
      positions 16, 17, and 19 hardly affected such activities. Analysis of another
      series of synthetic ET16-21 analogues with the His16 residue replaced by a non
      amino-acidic block confirmed that the last two C-terminal residues are essential
      for receptor and antibody binding, whereas the central region of this hexapeptide
      is much more tolerant to modification. However, a critical steric conformation of
      the active hexapeptide is necessary.

PMID- 9595453
TI  - Hemodynamic effect of endothelin antagonists in dogs with myocardial infarction.
AB  - The hemodynamic effects of enalapril, an angiotensin-converting enzyme inhibitor,
      BQ-123, a selective ETA receptor antagonist, and bosentan, a nonselective ETA and
      ETB receptor antagonist, were studied in dogs 4 weeks after myocardial infarction
      (MI) produced by ligation of the left anterior descending coronary artery.
      Reduced arterial pressure and total peripheral resistance after administration of
      analapril, BQ-123, and bosentan revealed that both the renin-angiotensin system
      and endothelin participate in maintenance of cardiovascular function in chronic
      MI.

PMID- 9595454
TI  - Hemodynamic and inotropic effects of the endothelin A antagonist BQ-610 in vivo.
AB  - The positive inotropy of endothelin-1 (ET-1) described by in vitro studies is not
      detectable in vivo because this effect is antagonized by cardiodepressive effects
      due to ET-induced vasoconstriction with subsequent myocardial ischemia. This
      vasoconstriction is mainly mediated by ETA receptors. In a previous in vivo study
      with a selective ETB receptor agonist, we showed that ETB receptors play an
      important role in the ET-induced positive inotropy. The present in vivo study
      examined whether selective ETA receptor blockade can unmask the ETB receptor
      mediated positive inotropy of endogenous ET-1 by preventing its cardiodepressive
      effects via ETA receptors. In an open-chest rat model, we compared the acute
      hemodynamic and inotropic effects of the highly selective ETA receptor antagonist
      BQ-610 (100 micrograms/kg) with NaCl controls during and after a 7-min infusion.
      In addition to measurements in the intact circulation, the effects on myocardial
      contractility were studied by isovolumic registrations (peak LVSP, peak
      dP/dtmax), which are independent of peripheral vascular effects. Acute blockade
      of the ETA receptors by BQ-610 had no effect on blood pressure and heart rate. BQ
      610 caused vasodilatation (total peripheral resistance -7.5% vs. control at the
      end of infusion; p < 0.01) with a consecutive increase in stroke volume (+15.3%;
      p < 0.01), cardiac output (+15.4%; p < 0.001), and ejection fraction (+10.4%; p <
      0.01). The isovolumic measurements indicated a significant positive inotropic
      effect of BQ-610 (peak LVSP + 4.2%, p < 0.01; peak dP/dtmax + 5.5%, p < 0.01).
      Therefore, selective ETA receptor blockade by BQ-610 improves the hemodynamics in
      the intact circulation by causing a reduction in afterload and an increase in
      myocardial contractility. The positive inotropic effect of BQ-610 may be mediated
      by the positive inotropy of endogenous ET-1 via ETB receptors after selective ETA
      receptor blockade.

PMID- 9595455
TI  - Hemodynamic effects of a selective endothelin--a receptor antagonist in
      deoxycorticosterone acetate-salt hypertensive rats.
AB  - The time-course changes in blood pressure (BP), cardiac output (CO), and total
      peripheral conductance (TPC) were investigated during a bolus i.v. infusion of
      BMS-182874, a selective ETA receptor antagonist, in conscious, unrestrained DOCA
      salt hypertensive rats and Sham-operated control rats (SHAM). BP was recorded
      with radiotelemetry devices and CO with ultrasonic transit-time flow probes. In
      contrast to vehicle-treated controls, BMS-182874 reduced BP and increased TPC in
      DOCA-salt hypertensive rats but not in SHAM-rats. A small increase in CO tended
      to oppose the BP-lowering effect of the antagonist. The results suggest that the
      role of ETA receptors in the maintenance of the hypertensive state in the DOCA
      salt model of hypertension is exerted at the level of the resistance vessels and
      not on factors that regulate CO.

PMID- 9595456
TI  - Differential modulation of the renal and myocardial endothelin system by
      angiotensin II in Vivo. Effects of chronic selective ETA receptor blockade.
AB  - Angiotensin II (Ang II) stimulates endothelin-1 (ET-1) production in glomerular
      endothelial and mesangial cells and in cardiac fibroblasts in vitro. We
      investigated the effects of Ang II in vivo (200 ng/kg/min for 2 weeks) with or
      without the ETA receptor antagonist LU135252 (50 mg/kg/day) on blood pressure,
      renal and myocardial ET-1 protein expression, and [125I]ET-1 uptake in male
      Wistar-Kyoto (WKY) rats. ET-1 was extracted from whole kidneys and ventricular
      myocardium and was measured by radioimmunoassay (pg ET-1/g tissue). Organ tissue
      uptake was calculated as percentage of total DPM recovered after i.v.
      administration of radiolabeled [125I]ET-1. Ang II treatment increased blood
      pressure by 35 +/- 3 mm Hg, which was partly reduced by LU135252 (15 +/- 2 mm Hg,
      p < 0.05). LU135252 in part prevented the impaired weight gain induced by Ang II
      (p < 0.05). Ang II induced a threefold increase in expression of ET-1 (pg/g
      tissue) in kidneys (from 19 +/- 2 to 58 +/- 10, p < 0.05), which was normalized
      by LU135252 (20 +/- 9, p < 0.05). In myocardial tissue, Ang II had only minor
      effects (5 +/- 1 vs. 3.6 +/- 1, n.s.). However, concomitant LU135252 treatment
      reduced myocardial ET-1 levels (1.4 +/- 0.4, p < 0.05 vs. Ang II and control).
      Ang II increased uptake of [125I]ET-1 in kidneys (from 6.9 +/- 0.1% to 10.9 +/-
      0.9% of total DPM, p < 0.05) but not in myocardium (1.45 +/- 0.26% vs. 1.59 +/-
      0.18% of total DPM), which was unaffected by LU135252 treatment. These data
      suggest that the kidney, but not the ventricular myocardium, is a target for Ang
      II-mediated activation of the ET system in vivo, leading to expression and uptake
      of ET-1. ETA antagonists may provide a new approach to inhibit production and
      effects of ET-1 in diseases associated with increased activity of the renin
      angiotensin system.

PMID- 9595458
TI  - Pharmacologic characterization of the novel, orally available endothelin-A-
      selective antagonist SB 247083.
AB  - Competition radioligand binding with [125I]ET-1 at human cloned ETA and ETB
      receptors demonstrated ET-A selective affinity by SB 247083 (Ki 0.41 and 467 nM,
      respectively). Accordingly, similar competitive, functional ETA receptor
      antagonism was observed. In vitro, SB 247083 exhibited a Kb of 3.5 +/- 0.3 nM (ET
      1--induced rat aortic contraction). SB 247083 was significantly less potent as a
      functional ETB antagonist (Kb 0.34 +/- 0.01 microM; S6c-induced rabbit pulmonary
      artery contraction). In contrast to ETB-selective and mixed ETA/B antagonists,
      and consistent with its ETA-selective profile, in vivo administration of SB
      247083 was not associated with an elevation in plasma ET-1 levels.
      Pharmacodynamic and pharmacokinetic studies revealed that SB 247083 was
      effectively absorbed from the gastrointestinal tract. A single bolus dose
      inhibited the hemodynamic actions of ET-1 for up to 8 h, consistent with a
      molecule shown to be 46% bioavailable. Therefore, the present study demonstrates
      that SB 247083, a unique chemical entity, represents a potent class of
      nonpeptide, orally active ETA-selective antagonists.

PMID- 9595457
TI  - Acute renal effects of endothelin-A blockade: interspecies differences.
AB  - The acute renal effects of LU135252 (LU), a selective endothelin-A (ETA) receptor
      antagonist, were studied in conscious rats after i.p. administration of 1-10
      mg/kg LU, and in clearance studies in anesthetized dogs during left intrarenal
      infusion of 0.01-0.1 mg/kg/min. In the rat (n = 12), LU (10 mg/kg i.p.) decreased
      diuresis (-36%), excretion of Na (-55%) and Cl (-38%) but not of K and
      creatinine, as measured in 8-h collections in metabolic cages. Excretion of oral
      NaCl load (5% of body weight) during 4 h decreased from 68 +/- 2% (vehicle) to
      50.5 +/- 5% (LU; n = 12, p < 0.01). Blood pressure was not affected. In contrast,
      left intrarenal LU infusion at 0.01, 0.03 and 0.1 mg/kg/min in the dog (n = 4)
      had no effect on renal hemodynamics or excretory function, whereas it mildly
      decreased blood pressure. In addition, intrarenal LU (0.03 mg/kg/ min; n = 6) had
      no effect on the renal response to volume expansion (7% bw) by 0.9% NaCl i.v.
      These markedly different effects of acute ETA blockade were observed at similar
      systemic plasma levels of LU in the two species. It is concluded that in the rat,
      but not in the dog, acute blockade of ETA receptors can impair renal excretory
      function, most likely at the tubule level. This interspecies difference in the
      role of endogenous ET in the regulation of renal function is probably due to a
      different ET receptor profile and distribution in rat and dog kidneys.

PMID- 9595459
TI  - Effects of endothelin receptor antagonism and angiotensin-converting enzyme
      inhibition on cardiac and renal remodeling in the rat.
AB  - The effects of a nonpeptide, orally active mixed endothelin (ET) ETA/ETB receptor
      antagonist, SB 217242, and an angiotensin-converting enzyme (ACE) inhibitor,
      ramipril, were evaluated after inter-renal aortic banding in the rat. Separate
      sham, vehicle, and treatment groups were compared in each study. In vehicle
      treated animals in the ramipril group, aortic banding for 4 weeks produced
      significant cardiac hypertrophy (247 +/- 5 mg/100 g bw vs. 305 +/- 11 mg/100 g
      bw; p < 0.001), right (upstream) renal hypertrophy (380 +/- 6 mg/100 g bw vs. 559
      +/- 28 mg/100 g bw; p < 0.001), and significant left (downstream) renal atrophy
      (405 +/- 4 mg/100 g bw vs. 192 +/- 25 mg/100 g bw; p < 0.001). Continuous
      ramipril treatment (1 mg/kg p.o. once daily), begun 3 days before aortic banding,
      inhibited cardiac hypertrophy (305 +/- 11 mg/100 g bw vs. 266 +/- 7 mg/100 g bw;
      p < 0.05) but did not alter renal hypertrophy or atrophy. In a similarly designed
      study, SB 217242 (30 mg/kg p.o. b.i.d.) had no effect on the development of
      cardiac hypertrophy (298 +/- 7 mg/100 g bw vs. 310 +/- 12 mg/100 g bw) or renal
      hypertrophy (561 +/- 15 mg/100 g bw vs. 575 +/- 19 mg/100 g bw), but abolished
      the development of renal atrophy (158 +/- 16 mg/100 g bw vs. 395 +/- 19 mg/100 g
      bw; p < 0.001). [125I]ET-1 radioligand binding experiments indicated that the
      density of both ETA and ETB receptors was increased dramatically (three- to
      fourfold) in the atrophic kidney cortex compared to sham or hypertrophic kidneys.
      In situ hybridization studies indicate an upregulation of ETB receptor mRNA in
      the glomeruli of atrophic kidneys within 5 days of aortic banding. In conclusion,
      an angiotensin-dependent mechanism may mediate cardiac hypertrophy associated
      with aortic banding, whereas ET-dependent mechanisms may mediate an atrophic
      response in the hypoperfused kidney, perhaps through an interaction with
      upregulated ETA and/or ETB receptors.

PMID- 9595460
TI  - Ethanol reduces the endothelin-B receptor-mediated increase in portal inflow
      resistance in the isolated, perfused canine liver.
AB  - Ethanol can affect the regulation of liver hemodynamics through the release of
      vasoactive mediators such as nitric oxide and endothelins (ETs). The purpose of
      this study was to investigate the effects of ethanol on the changes in arterial
      and portal perfusion pressure induced by ET receptor activation. Ethanol
      significantly reduced portal, but not arterial perfusion pressure. ET-1 and
      norepinephrine (used as an ET receptor-independent vasoconstrictor) induced
      changes in hepatic arterial or portal inflow resistance that were not affected by
      ethanol treatment. However, an IRL 1620-induced increase in portal, but not
      arterial, inflow resistance was significantly reduced in ethanol-perfused
      preparations, an effect observed after either intra-arterial or intraportal
      administration of the agonist. These results suggest that ethanol can diminish
      the responsiveness of the portal vascular bed of the canine liver to ETB receptor
      activation.

PMID- 9595461
TI  - High pericardial fluid levels of endothelin are not caused by altered neutral
      endopeptidase activity in cardiac patients.
AB  - We have previously detected in cardiac patients severalfold higher levels of
      endothelin (ET) in the pericardial fluid (PF) than in the plasma (PL). We
      postulated that this is due to different activities of neutral endopeptidase
      (NEP) in the two compartments. With approval of the ethical committee and
      informed consent by 32 patients (18 men, 14 women, aged 62 +/- 2 years; NYHA II
      IV), PF was taken during cardiac surgery. PL samples were obtained on the day of
      surgery before premedication. ET was measured by radioimmunoassay after
      extraction (SepPakC18). NEP activity was measured by a microplate-based kinetic
      enzyme assay over 120 min. PF ET (78 +/- 11 pg/ml) was significantly (p < 0.05)
      higher than PL ET (3.38 +/- 0.48 pg/ml). The PF/PL ratio was 38 +/- 14, range 7
      200. PF ET was inversely related to the NYHA state of the patients, whereas a
      similar relation was not found with PL ET. PL and PF ET levels did not correlate.
      In HPLC, the total immunoreactive ET activity co-eluted with the human ET
      standard. PF NEP activity (2.26 +/- 0.12 U/l) was lower (p < 0.05) than PL NEP
      (3.62 +/- 0.22 U/I). PL NEP was not different from that of healthy controls (3.28
      +/- 0.22 U/L; n = 50). No correlation was found between NEP in either compartment
      and the NYHA state of the patients. ET concentration and NEP activity did not
      correlate in PF or PL. We conclude that ET is extremely high in the PF of cardiac
      patients and that this is not caused by altered NEP activity.

PMID- 9595462
TI  - Pulmonary and systemic responses to exogenous endothelin-1 in patients with left
      ventricular dysfunction.
AB  - Plasma levels of immunoreactive endothelin-1 (ET-1) are elevated in chronic heart
      failure (CHF) and have been reported to correlate closely with pulmonary
      hemodynamic measurements. We investigated the effects of exogenous ET-1 on the
      pulmonary vasculature in patients with left ventricular systolic dysfunction
      (LVD), with or without overt heart failure. ET-1 was infused at 1, 5, and 15
      pmol/min into a distal pulmonary artery of 10 patients with LVD. Hemodynamics
      were measured by a thermodilution catheter and arterial line. Intravascular
      Doppler and local pulmonary angiography were used to assess local pulmonary blood
      flow in the first four patients. Systemic hemodynamic changes occurred with ET-1
      infusion in a dose-dependent fashion. Mean arterial pressure (100 +/- 8-107 +/-
      11 mm Hg; p < 0.01) and systemic vascular resistance (1,699 +/- 375-2,033 +/- 427
      dynes/s/cm-5; p < 0.001) rose, whereas the cardiac index fell from 2.43 +/- 0.53
      to 2.20 +/- 0.491/min/m2 (p < 0.002). However, mean pulmonary artery pressure (21
      +/- 7 mm Hg) and pulmonary vascular resistance (151 +/- 43-147 +/- 43 dynes/s/cm
      5) did not change. Exogenous ET-1, when infused into patients with LVD, causes
      systemic but not pulmonary vasoconstriction.

PMID- 9595463
TI  - Coordinated upregulation of the cardiac endothelin system in a rat model of heart
      failure.
AB  - The potent vascular, cardiac, and renal actions of endothelin-1 (ET-1) suggest a
      role for this vasoconstrictor peptide in the pathophysiology of heart failure
      (HF). Recent studies have shown increased levels of ET-1 peptide accompanied by
      increased ETB receptor binding in the left ventricle during experimental HF.
      However, much less is known about the regulation of mRNA expression of these
      genes in HF. We compared the levels of mRNA expression for ET-1 and ET receptors
      (ETA and ETB) in the left ventricle of rats with HF induced by coronary artery
      ligation (n = 6) vs. sham-operated animals (n = 6). Levels of mRNA for ET-1 were
      determined by ribonuclease protection assay (RPA) using beta-actin as the
      internal control, whereas ET receptors were quantified by quantitative
      competitive RT-PCR. Compared with sham animals, ET-1, ETA, and ETB receptor mRNA
      levels were markedly upregulated in the left ventricle by 6.6 +/- 1.8-fold (p <
      0.01), 3.2 +/- 0.6-fold (p < 0.05), and 3.5 +/- 1.0-fold (p < 0.05),
      respectively. ET-1 mRNA levels were measured in two additional groups of rats (HF
      and sham; n = 6 each) treated for 4 weeks with the selective ETA receptor
      antagonist LU135252. This treatment had no significant effect on ET-1 mRNA
      expression in sham animals but reduced the upregulation of ET-1 expression in the
      HF group by 41 +/- 19% (p < 0.05). This study confirms the potential importance
      of ET-1 in HF and suggests that increased expression of ET-1 and ET receptors in
      the failing ventricle may contribute to alteration in basal cardiac contractility
      and myocardial remodeling.

PMID- 9595464
TI  - Cloning of hamster preproendothelin-1 cDNA and its expression in the heart.
AB  - To elucidate the pathophysiologic roles of endothelin-1 (ET-1) in the heart, we
      first cloned and sequenced a part of hamster preproET-1 cDNA from the heart of
      the CHF146 hamsters. The amino acid sequence has 89% homology to that of rat
      preproET-1 in the cloned part. The deduced hamster 21-residue mature ET-1 is
      identical to human, rat, canine, and mouse ET-1. In the next step we investigated
      the expression of preproET-1 mRNA in the failing heart of CHF146 hamsters. For
      this purpose, we used 46-week-old CHF146 hamsters and age-matched control healthy
      hamsters. Left ventricular (LV) + dP/dtmax was significantly lower in CHF146
      hamsters than in control hamsters. LV end-diastolic pressure was significantly
      higher in CHF146 hamsters than in control hamsters, as was central venous
      pressure. These results suggested that the CHF146 hamsters developed congestive
      heart failure. The expression of preproET-1 mRNA was greatly enhanced in the LV
      of the CHF146 hamsters. Because it has been reported that ET-1 induces cardiac
      hypertrophy and injury to cardiac myocytes in addition to its potent positive
      inotropic and chronotropic actions, the present findings suggest that endogenous
      ET-1 plays pathophysiologic roles in the failing heart of CHF146 hamsters.

PMID- 9595465
TI  - Altered expression of isoforms of myosin heavy chain mRNA in the failing rat
      heart is ameliorated by chronic treatment with an endothelin receptor antagonist.
AB  - We have reported that the production of endothelin (ET)-1 is markedly increased
      in the failing heart of rats with chronic heart failure (CHF) and that the long
      term (3-month) treatment with the ETA receptor antagonist BQ-123 markedly
      ameliorated the long-term survival and hemodynamic parameters in rats with CHF.
      In this study we investigated whether this therapy affects the alteration of the
      mRNA expression of cardiac myosin heavy chain (MHC) isoforms in the hearts of
      rats with CHF. The change from alpha-MHC to beta-MHC is regarded as a molecular
      marker for heart failure. The expression of beta-MHC mRNA was dominant in the
      left ventricle (LV) of CHF rats treated with saline, whereas that of alpha-MHC
      was dominant in the LV of sham-operated rats treated with saline. Therefore, in
      the failing rat heart, a change from alpha-MHC to beta-MHC occurred. In the LV of
      CHF rats treated with BQ-123, this treatment effectively prevents the switching
      of MHC isoforms. These findings suggest that long-term BQ-123 treatment inhibits
      the change in MHC isoforms and suggest that this treatment ameliorates heart
      failure in CHF rats at the molecular level.

PMID- 9595466
TI  - Chronic endothelin-1 blockade preserves myocardial contractility in dilated
      cardiomyopathy.
AB  - Endothelin-1 (ET-1) is known to have positive inotropic effects in isolated
      cardiac muscle strips. ET-1 levels are elevated in congestive heart failure
      (CHF). We investigated the effects of ET-1 on contractility and cardiac
      relaxation (lusitropy) of the intact healthy murine heart and
      myocarditic/cardiomyopathic heart by chronic oral treatment with a mixed ETA/ETB
      blocker SB217242. Chronic ET-1 blockade of normal hearts resulted in depression
      of contractility and lusitropy of the normal heart but preservation and
      enhancement of contractility and lusitropy in myocarditic animals, in which ET-1
      cardiac content is elevated. This suggests that ET-1 is important in the basal
      contractility and relaxation of the normal heart but that its chronic elevation
      in CHF causes impairment of cardiac systolic and diastolic performance.

PMID- 9595467
TI  - Vascular endothelin-1 expression and effect of an endothelin ETA antagonist on
      structure and function of small arteries from stroke-prone spontaneously
      hypertensive rats.
AB  - There is some evidence that the endothelin (ET) system may participate in blood
      pressure elevation and in vascular hypertrophy in stroke-prone spontaneously
      hypertensive rats (SHR-SP). To further understand the involvement of the ET
      system in this hypertensive model, we examined preproendothelin-1 (preproET-1)
      mRNA abundance in blood vessels of 5-week and 18-week SHR-SP in comparison to
      SHR, and treated 12-week old SHR-SP with the ETA-selective receptor antagonist A
      127722.5 (30 mg/kg/day in the drinking water) for 10 weeks. Abundance of preproET
      1 mRNA by Northern blot analysis was increased more than twofold in aorta and
      mesenteric arteries of SHR-SP relative to SHR at 18 weeks but not at 5 weeks of
      age. SHR-SP treated with A-127722.5 had a tail-cuff systolic blood pressure at 22
      weeks of age of 241 +/- 2 mm Hg vs. 251 +/- 3 mm Hg in untreated SHR-SP (p <
      0.05). Heart:body weight ratio was no different in both groups, but aortic
      segment:body weight ratio was slightly but significantly smaller in treated SHR
      SP (p < 0.05). Pressurized mesenteric small arteries from treated SHR-SP had a
      smaller media width (12.6 +/- 0.6 microns vs. 14.9 +/- 0.5 microns; p < 0.05) and
      media:lumen ratio (5.8 +/- 0.2% vs. 7.3 +/- 0.3%; p < 0.01), whereas media cross
      sectional area and lumen diameter tended to decrease and increase, respectively,
      without achieving statistical significance. Acetylcholine-induced relaxation was
      improved in treated SHR-SP (99.6 +/- 0.6% vs. 90.0 +/- 3.6%; p < 0.05), whereas
      relaxation responses to sodium nitroprusside were similar in both groups. These
      results show increases of preproET-1 expression in blood vessels that appear to
      be secondary to blood pressure elevation. There is a small ET-dependent component
      in blood pressure elevation and in conduit and resistance artery changes in adult
      stroke-prone SHR.

PMID- 9595468
TI  - Tetramethylpyrazine, a Chinese drug, blocks coronary vasoconstriction by
      endothelin-1 and decreases plasma endothelin-1 levels in experimental animals.
AB  - The purpose of this study was to investigate effects of tetramethylpyrazine
      (TMP), a Chinese plant-derived medicine, on coronary vasoconstriction and related
      electrocardiographic and histologic changes caused by endothelin-1 (ET-1), and on
      plasma ET-1 levels. ET-1 (75 pmol) was administered into the left coronary artery
      (LCA) in anesthetized closed-chest dogs with and without prior infusion of TMP
      (80 mg/kg). Coronary arterial diameter (CAD) was determined by coronary
      arteriography (CAG). Blood pressure and electrocardiogram (ECG) were monitored
      continuously. Histologic damage in tissues was ascertained microscopically.
      Plasma ET-1 and 6-keto-PGF1 levels were determined by RIA 90 min after i.v.
      injection of TMP (25 mg/kg; n = 5) in rabbits. Intracoronary injection of ET-1
      resulted in a significant vasoconstriction of the entire vascular bed of the LCA,
      with a decrease in CAD of 35.9 +/- 5.7% (n = 5; p < 0.01) and ischemic changes on
      ECG and in tissues of endocardium, myocardium, coronary endothelial cells, and
      capillary vessels. Pretreatment with TMP produced a significant increase in CAD
      by 38.5 +/- 7.8% (n = 5; p < 0.01) and greatly suppressed the vasoconstriction
      produced by ET-1. The myocardial tissue damage estimated from the ratio of
      ischemic area for the entire area after ET-1 injection (35.6%) was completely
      abolished by TMP (0.6%). In addition, TMP injection induced a significant
      decrease in plasma ET-1 levels and an increase in 6-keto-PGF1 levels in rabbits.
      The Chinese medicine TMP could be a useful therapeutic agent in ischemic heart
      disease by suppressing coronary vasoconstriction and ischemic changes in the
      tissues produced by ET-1.

PMID- 9595469
TI  - Application of magnetic resonance imaging for evaluation of the efficacy of SB
      217242 in neointimal formation.
AB  - Although several factors have been implicated in the pathophysiology of vascular
      neointimal formation and restenosis after balloon angioplasty, current therapies
      have failed to alleviate these conditions. Because endothelin-1 (ET-1) has been
      implicated in the pathogenesis of the neointimal growth, this study examined the
      in vivo efficacy of SB 217242, a potent nonpeptide mixed ETA/ETB receptor
      antagonist with high oral bioavailability, in the rat carotid balloon angioplasty
      model. A novel magnetic resonance imaging (MRI) approach was used for evaluation.
      MRI is a high-resolution, noninvasive spatial imaging modality that can serially
      monitor arterial luminal caliber in vivo, along with histologic evaluation. In
      vivo luminal volumes for the left carotid artery (LCA) were measured by MRI at
      baseline (before surgery) and again at 14 days after angioplasty. SB 217242 (30
      mg/kg/day p.o.) was administered daily for 14 days after angioplasty. On day 14,
      SB 217242 provided 20% protection (p < 0.05) on neointimal-mediated decrease in
      luminal volume as measured by MRI. The non-ballooned right carotid arteries of
      both groups had significantly increased luminal volume on day 14 with respect to
      baseline values, indicating compensation for the decreased luminal size of the
      LCA. Histologic analysis of the mean intimal-to-medial ratio demonstrated that SB
      217242 provided 42% (p < 0.05) protection. These results demonstrate that ET
      receptor antagonism can inhibit neointimal formation after balloon angioplasty
      and that MRI technology can provide valuable insight for noninvasive assessment
      of vascular lesion development.

PMID- 9595470
TI  - Attenuation of experimental subarachnoid hemorrhage-induced cerebral vasospasm by
      CGS 26303, an endothelin-converting enzyme inhibitor.
AB  - The effect of CGS 26303, an endothelin-converting enzyme inhibitor, on the
      prevention and reversal of cerebral vasospasm was investigated in a rabbit model
      of subarachnoid hemorrhage (SAH). In the prevention study, rabbits were injected
      with 3 ml of autologous blood in the cisterna magna and treatment with CGS 26303
      i.v. was initiated 1 h later. The compound was subsequently administered at 12,
      24, and 36 h post SAH and animals were sacrificed at 48 h post SAH. Treatment
      with CGS 26303 at 3, 10, and 30 mg/kg resulted in dose-dependent increases in the
      concentrations of the compound in cerebrospinal fluid samples, and the arterial
      narrowing after SAH was significantly attenuated in all three groups.
      Morphologically, corrugation of the internal elastic lamina of vessels was often
      observed in the vehicle-treated group, but it was not prominent in the CGS 26303
      treated groups and the healthy controls. In the reversal study, treatment with
      CGS 26303 was initiated 24 h post SAH and a second injection was given 12 h
      later. Arterial narrowing was significantly attenuated in rabbits treated with
      CGS 26303 at 30 mg/kg. These results demonstrate that CGS 26303 may be an
      effective agent in prevention and reversal of cerebral vasospasm after aneurysmal
      SAH.

PMID- 9595471
TI  - Expression of endothelial factors after arterial injury in the rat.
AB  - Endothelin-1 (ET-1) and nitric oxide (NO) are potent vasoactive factors known to
      play a role in vascular remodeling. This study assessed the temporal expression
      of endothelial NO synthase (eNOS), preproET-1, and ETA and ETB receptor mRNAs in
      the rat carotid artery after balloon injury using quantitative competitive
      reverse transcription-polymerase chain reaction (qcRT-PCR) and the ribonuclease
      protection assay (RPA). Levels of ET-1 increased sharply after arterial injury,
      peaking (5.1-fold) at 2 days. This was associated with a dramatic increase in the
      expression of ETB (63-fold) and ETA (158-fold) receptor mRNA, peaking at days 1
      and 2, respectively. Expression of eNOS was not detectable immediately after
      balloon injury, consistent with complete denudation, but reappeared after day 2
      and increased to preinjury levels by day 14. The recovery of eNOS expression
      mirrored the return of ET-1 and ET receptor expression to baseline levels. The
      results confirm profound upregulation of the ET system in this model of arterial
      injury and suggest a critical role for eNOS expression and re-endothelialization
      in the normalization of ET-1 and ET receptor expression during the recovery
      phase, events that may be important in long-term arterial patency.

PMID- 9595472
TI  - Endothelin-1 and endothelin receptors in porcine saphenous vein-carotid artery
      grafts.
AB  - The regional distribution of endothelin-1 (ET-1) and its receptor subtypes (ETA
      and ETB) in porcine saphenous vein into carotid artery interposition grafts was
      studied 1 month after surgery and compared to ungrafted saphenous vein and
      carotid artery. ET-1 immunoreactivity was identified by immunohistochemistry and
      ET receptor subtypes were studied using in vitro autoradiography. In vein grafts,
      there was a higher density of ETA compared to ETB receptor binding in both the
      tunica media and the neointima. ETA binding to the tunica media of ungrafted
      saphenous vein was greater than that in the carotid artery or vein grafts, but
      greater in the vein graft compared to the carotid artery. Immunoreactive ET-1 was
      located in endothelial cells and throughout the neointima of the vein graft.
      Dense ETA and ETB binding was also associated with adventitial microvessels in
      the graft, and ETB binding was also identified to neutrophils, which accumulated
      at the subendothelium and within the adventitia. ETA receptors may play a role in
      vein graft thickening at the medial and neointimal vascular smooth-muscle cell
      level, whereas ETB receptors may play a role in microangiogenesis. The high
      levels of ETA receptors in the tunica media of ungrafted saphenous vein, relative
      to the carotid artery and vein graft, may also render this conduit susceptible to
      neointimal formation. These data indicate that studies of the effect of ET
      receptor antagonists on the pathobiology of vein graft disease are warranted.

PMID- 9595473
TI  - Efficacy of CI-1020, an endothelin-A receptor antagonist, in hypoxic pulmonary
      hypertension.
AB  - We previously showed that CI-1020, an endothelin (ET)-A-selective receptor
      antagonist, dose-dependently blocked acute hypoxic pulmonary hypertension (PH) in
      rats. In this study we show that CI-1020 can reverse existing PH and prevent
      progression of right ventricular hypertrophy (RVH) in rats exposed to chronic
      hypoxia. Male Sprague-Dawley rats were exposed to 20 days of hypoxia (10% O2)
      with CI-1020 treatment (20 or 40 mg/kg/day) starting on day 10. On day 20 of
      hypoxia, the rats were instrumented under anesthesia with a pulmonary artery
      cannula and allowed to recover to consciousness before measurement of mean
      pulmonary arterial pressure (MPAP). Blood samples were then collected for plasma
      ET-1 measurements, the rats killed, and their hearts dissected, dried, and
      weighed. RV/LV + septum ratio (g/g) was used as an index of RVH (RVHi). Normoxic
      rats and rats exposed to hypoxia for only 10 days were also evaluated as
      controls. Normoxic rats had MPAPs of 13 +/- 1 mm Hg, plasma ET-1 levels of 2.1 +/
      0.1 pg/ml, and an average RVHi of 0.29 +/- 0.03. Rats exposed to 10 or 20 days
      of hypoxia had MPAPs of 33 +/- 2 and 44 +/- 0 mm Hg, plasma ET-1 levels of 4.2 +/
      0.8 and 4.6 +/- 0.8 pg/ml, and average RVHis of 0.47 +/- 0.05 and 0.52 +/- 0.03,
      respectively. In comparison, rats treated with CI-1020 had MPAPs that were 37%
      (20 mg/kg/day) and 44% (40 mg/kg/day) lower than untreated 20-day hypoxic rats.
      Furthermore, rats dosed with 40 mg/kg/day of CI-1020 had MPAPs that were
      significantly lower (24%) than control 10-day hypoxic rats, indicating a
      significant reversal of PH. Along with this reversal in PH, their average RVHi
      was 23% lower (p < 0.05) relative to untreated 20-day hypoxic rats.

PMID- 9595474
TI  - Pulmonary disease models induced by in vivo hemagglutinating virus of Japan
      liposome-mediated endothelin-1 gene transfer.
AB  - Overproduction and overexpression of endothelin-1 (ET-1) have been reported to
      contribute to the pathophysiology of pulmonary diseases, including pulmonary
      fibrosis, obliterative bronchiolitis, and primary pulmonary hypertension. To
      determine whether ET-1 contributes to the pathogenesis of pulmonary disease, we
      locally overexpressed ET-1 using an in vivo UV-inactivated hemagglutinating virus
      of Japan (HVJ) liposome-mediated gene transfer system. Plasmid DNA of ET-1
      (pME18fc preproET-1) and high mobility group 1 (HMG1) protein were co
      encapsulated in liposomes. Then the plasmid DNA and liposome complexes were
      introduced into the lung via the trachea in Wistar rats, using HVJ-mediated
      membrane fusion. Control animals received instillation of HVJ liposome with an
      empty cassette. Two weeks after in vivo transfection of the preproET-1 gene,
      hyperplastic connective tissue plaques were seen in the alveolar duct and small
      conducting airways, indicating histologically distinctive obliterative
      bronchiolitis. No histopathologic changes were seen in the control animals. These
      results suggested that local overexpression of ET-1 may play an important role in
      the pathogenesis of obliterative bronchiolitis.

PMID- 9595475
TI  - SB 234551, a novel endothelin--A receptor antagonist, unmasks endothelin-induced
      renal vasodilatation in the dog.
AB  - Infusion of endothelin-1 (ET-1) into conscious, chronically instrumented dogs (10
      ng/kg.min i.v.) resulted in a significant increase in mean arterial pressure and
      significant reductions in renal plasma flow, glomerular filtration rate, and
      sodium excretion. Intravenous infusion of SB 209670 (30 micrograms/kg.min, i.v.)
      abolished these responses, whereas infusion of SB 234551 (30 micrograms/kg.min,
      i.v.) resulted in significant increases in renal plasma flow and urinary sodium
      excretion. These data indicate that SB 234551 can unmask ETB receptor-induced
      renal vasodilatation and inhibition of sodium reabsorption.

PMID- 9595476
TI  - The Endothelin system in polycystic kidneys of Han:SPRD rats.
AB  - Polycystic kidney disease (PKD) is characterized by structural alterations such
      as thickening of the tubule basement membrane, interstitial fibrosis, and
      formation of cysts. Han:SPRD rats are a well-known rat model of human PKD.
      Interestingly, interstitial fibrosis, glomerulosclerosis, and cyst formation were
      also seen in human endothelin-1 (ET-1) transgenic mice. We therefore analyzed the
      tissue concentrations of ET-1 and the expression of ET receptor subtypes in the
      kidneys of young homozygous (cy/cy), heterozygous (cy/+) 6 week-old male
      Han:SPRD, and corresponding control rats. The kidneys of affected rats showed
      significantly elevated tissue levels of ET-1 compared to age-matched controls.
      Scatchard analysis, on the other hand, revealed markedly decreased ETA and ETB
      receptor density in all groups of affected rats. The binding affinity of both ET
      receptor subtypes was slightly decreased in Han:SPRD rats. These data show that
      the renal paracrine ET system is activated in PKD and might contribute to renal
      cyst formation and development of end-stage kidney disease.

PMID- 9595477
TI  - Oxidative stress suppresses the endothelial secretion of endothelin.
AB  - To address endothelial function on vascular walls exposed to oxidative stress, we
      investigated the effect of oxidative stress on the secretion of endothelin-1 (ET
      1) from cultured bovine carotid artery endothelial cells (BAECs). Concentrations
      of ET-1 in the media were measured by a specific radioimmunoassay and ET-1 mRNA
      expression was estimated by Northern blot analysis. Treatment of BAECs with 0.5
      2.0 mM H2O2 for 3 h suppressed both ET-1 secretion and ET-1 mRNA expression in a
      dose-dependent manner compared to control. Attenuation of ET-1 mRNA expression by
      H2O2 was revealed to take place at the transcriptional level. The addition of NG
      nitro-L-arginine-methyl ester (L-NAME) 10 microns, a specific nitric oxide
      synthase inhibitor, had no effect on H2O2-induced suppression of ET-1 mRNA
      expression. Suppression of ET secretion under oxidative stress observed in the
      present study is proposed to be a compensatory mechanism of endothelial cells to
      inhibit vasoconstriction and proliferation during oxidative stress.

PMID- 9595478
TI  - Cytokine and lipopolysaccharide stimulation of endothelin-1 release from human
      internal mammary artery and saphenous vein smooth-muscle cells.
AB  - Many pathologic conditions are associated with elevations in the production of
      endothelin-1 (ET-1) in the blood vessel wall. Because many of these conditions
      are cytokine-driven we examined the effects of a mixture of cytokines and
      lipopolysaccharide on ET-1 production in human vascular smooth-muscle (VSMC)
      cells derived from the internal mammary artery (IMA) and saphenous vein (SV).
      Incubation of VSMCs from IMA and SV with a combination of tumor necrosis factor
      alpha (10 ng/ml), interferon-gamma (1,000 U/ml), interleukin-1 beta (500 U/ml)
      and lipopolysaccharide (10 micrograms/ml) for up to 48 h markedly elevated the
      expression of mRNA for ET-1 and the release of ET-1 into the culture medium. We
      conclude that low levels of ET-1 mRNA and peptide production in human VSMCs are
      markedly increased by exposure to cytokines and LPS. This suggests that during
      inflammatory states the VSMC, as well as the endothelium, may be a site of
      significant ET-1 production in the blood vessel wall.

PMID- 9595479
TI  - Endothelin-1 enhances nitric oxide-induced cell death in cultured vascular smooth
      muscle cells.
AB  - Increased expression of endothelin-1 (ET-1) immunoreactivity is demonstrated in
      the active atherosclerotic plaque. Here we show that both ETA and ETB receptors
      are expressed in rat vascular smooth-muscle cells (VSMCs). ET-1 binding to ETB
      receptors enhances nitric oxide-induced cell death in VSMCs. These findings
      suggest that ET-1 may participate in the mechanism of cell death (apoptosis) in
      the plaque through activation of ETB-mediated pathways and that a selective ETB
      receptor antagonist could be useful in preventing acute plaque alterations, such
      as plaque rupture.

PMID- 9595480
TI  - Endothelin-1 and cardiotrophin-1 induce brain natriuretic peptide gene expression
      by distinct transcriptional mechanisms.
AB  - Cardiotrophin-1 (CT-1) a novel IL-6-related cytokine, induces distinct
      hypertrophic responses to endothelin-1 (ET-1) on cultured neonatal rat cardiac
      myocytes. We found that ET-1 and CT-1 show a distinct pattern of gene induction
      of natriuretic peptides. Elucidation of the transcriptional mechanisms of brain
      natriuretic peptide (BNP) gene induction by. ET-1 or CT-1 will provide better
      information for our understanding of the molecular mechanisms of cardiac
      hypertrophy. In this study, reporter constructs containing the human BNP 5'
      flanking sequence were transfected into neonatal rat cardiac myocytes and the
      cells were stimulated with ET-1 or CT-1. A total of 1813 bp of the human BNP 5'
      flanking sequence conferred an ET-1 inducibility on the reporter gene. However,
      it did not confer CT-1 inducibility. These results show that distinct mechanisms
      are involved in BNP gene induction by ET-1 or CT-1, and (in this study) that the
      CT-1 responsive element is not located in the region examined.

PMID- 9595481
TI  - Interaction of myocytes and nonmyocytes is necessary for mechanical stretch to
      induce ANP/BNP production in cardiocyte culture.
AB  - In cardiac hypertrophy or ventricular remodeling, enlargement of myocytes and
      interstitial or perivascular fibrosis are observed simultaneously, which suggests
      an interaction between cardiac myocytes and fibroblasts. In this study we
      examined the mechanism of cyclic mechanical stretch-induced myocytic hypertrophy,
      focusing on the interaction between myocytes and cardiac nonmyocytes, mostly
      fibroblasts. Ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs) were
      separately extracted from neonatal rat ventricles by the discontinuous Percoll
      gradient method and primary cultures of cardiac cells were prepared. When MCs
      were co-cultured with NMCs, the size of MCs and the ANP/BNP secretion were
      significantly increased. This hypertrophic change of MCs in the co-culture was
      significantly suppressed by BQ-123, an endothelin-A (ETA) receptor antagonist.
      Cyclic stretch did not induce hypertrophic responses in MC culture. However, it
      further increased ANP/BNP production in MC-NMC co-culture (2.2-fold and 2.1-fold
      increases vs. non-stretch group after 48-h incubation). This increase in ANP/BNP
      production in the co-culture was significantly suppressed by CV-11974, an
      angiotensin II (Ang II) type 1 receptor antagonist. This study raises the
      possibility that NMCs regulate cardiocyte hypertrophy via secretion of endothelin
      1 and that Ang II is involved in the interaction between MCs and NMCs during the
      course of hypertrophic response of cardiocytes to mechanical stretch.

PMID- 9595482
TI  - Endothelins: effect on matrix biosynthesis and proliferation in normal and
      scleroderma fibroblasts.
AB  - We investigated the effect of endothelin-1 (ET-1) in normal and systemic
      sclerosis (SSc) dermal fibroblasts. Collagen type I, collagen type III, and MMP-1
      levels in culture supernatants were measured by competition ELISA and cellular
      mRNA expression was examined by Northern blotting. Mitogenic responses to ET-1
      were assessed by [3H]TdR incorporation. ET receptor mRNA expression was examined
      by RT-PCR analysis of fibroblast RNA and with surface binding studies using
      radiolabeled ET receptor ligands and specific receptor antagonists. ET-1 enhanced
      release of collagen types I and III by control and SSc fibroblast strains, but
      the effects were significantly greater for control cells (p < 0.05). This effect
      appeared to involve both ETA and ETB receptor subtypes. SSc fibroblasts
      demonstrated lower constitutive MMP-1 production than control fibroblasts (p <
      0.01), but ET-1 treatment decreased MMP-1 in normal fibroblasts to levels
      observed in SSc. Mitogenic response (percent control [3H]TdR incorporation) to ET
      1 for SSc fibroblasts was 130 +/- 34, significantly less (p < 0.01) than that for
      normal fibroblasts strains (290 +/- 25). This response appeared to be
      predominantly mediated via the ETA receptor subtype. Surface binding studies
      suggested a significantly lower level of ETA binding sites in SSc compared with
      normal fibroblasts (p < 0.05). These data suggest that ET-1 induces a fibrogenic
      phenotype in normal dermal fibroblasts that resembles that seen in fibroblasts
      grown from lesional SSc skin. Moreover, SSc cells appear to be refractory to
      these effects, and this reduced responsiveness is associated with an altered
      ratio of ETA:ETB receptor expression, supporting a role for ET-1 in the fibrotic
      pathology of SSc.

PMID- 9595483
TI  - Single-cell characterization of endothelin system gene expression in the
      cerebellum in situ.
AB  - To evaluate the expression of components of the endothelin (ET) system in single
      Purkinje neurons and Bergmann glial cells in situ, patch-clamp recording was
      combined with a multiplex RT-PCR approach. Cerebellar slices were rapidly
      isolated from 20- to 28-day-old mice. Cells were characterized morphologically
      and electrophysiologically and cell contents were aspirated and immediately
      reverse-transcribed. The cDNA was used as a template in a multiplex PCR reaction
      containing primers specific for ET-1, ET-2, and ET-3, ET-converting enzyme 1 (ECE
      1) and ECE-2, and ETA and ETB receptors. The resulting PCR products were used as
      templates in a second PCR reaction containing only one pair of nested primers.
      Specific single bands were obtained from positive cells, which was confirmed by
      DNA sequencing of the PCR products. Of the 25 Purkinje neurons assayed, 84% were
      positive for ECE-1 mRNA and 68% for ECE-2 mRNA. No ET and ETA receptor mRNAs were
      detected, and only one cell was positive for ETB receptor mRNA. In Bergmann glial
      cells, ETB receptor mRNA was predominant. A total of 68% of the 25 cells assayed
      were positive. Sixteen percent were positive for ETA receptor mRNA, 8% for ECE-1
      mRNA, and 12% for ECE-2 mRNA. Again, no ET mRNAs were detected. These results
      confirm the role of the ETB receptor in Bergmann glial cells and provide evidence
      for expression of ECE-1 and ECE-2 in Purkinje neurons.

PMID- 9595484
TI  - Production and secretion of endothelin-1 by cultured choroid plexus carcinoma
      cells.
AB  - Choroid plexus carcinoma is a rare neoplasm derived from the epithelium of the
      choroid plexus. The production and secretion of endothelin-1 (ET-1) by cultured
      human choroid plexus carcinoma cells were studied by radioimmunoassay and
      Northern blot analysis. Immunoreactive (IR)-ET was detected in the culture medium
      (2.78 +/- 0.12 fmol/10(5) cells/24 h; n = 5; mean +/- SEM) but not in the
      unconditioned medium. Reverse-phase high-performance liquid chromatography of the
      extract of the culture medium showed a single peak eluting in the position of ET
      1. Treatment with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL
      1 beta) or a combination of interferon-gamma (IFN-gamma), TNF-alpha, and IL-1
      beta caused significant increases in the IR-ET levels in the culture medium.
      Northern blot analysis of total RNA showed the expression of ET-1 mRNA in choroid
      plexus carcinoma cells. The expression levels of ET-1 mRNA were increased by
      treatment with a combination of IFN-gamma, TNF-alpha, and IL-1 beta. The present
      study has shown the production and secretion of ET-1 by cultured human choroid
      plexus carcinoma cells and suggests the possibility that ET-1 formation is
      related to the pathophysiology of this tumor.

PMID- 9595485
TI  - Regulation of endothelin release from human brain microvessel endothelial cells.
AB  - After approval by the Local Ethical Committee, brain microvessel endothelial
      cells from human cadavers were isolated by enzymatic digestion and gradient
      centrifugation. Basal levels of endothelin-1 (ET) in the supernatant increased
      over time (3 h, 18.3 +/- 4.3 pg/ml; 6 h, 31.3 +/- 1.1 pg/ml; 24 h, 88.0 +/- 5.7
      pg/ml; 48 h, 86.3 +/- 11.2 pg/ml, mean +/- SD). Tumor necrosis factor-alpha (TNF
      alpha) (270 U/ml) increased ET concentration dose-dependently: 3 h, 190 +/- 70%;
      24 h, 217 +/- 39%; 48 h, 207 +/- 5%; TNF-alpha at 210 U/ml: 3 h, 137%; 24 h,
      170%; 48 h, 212% (values are relative changes from control, run in parallel to
      the stimulated wells). Interleukin-1 alpha (IL-1 alpha) (38.8 U/ml) also
      increased ET dose-dependently: (3 h, 129%; 24 h, 161%; 48 h, 212%; IL-1 alpha 1.4
      U/ml: 3 h, 116%; 24 h, 122%; 48 h, 180%). Lipoprotein (a) (Lp(a)) had a dual
      effect on ET, increasing ET in the first 3 h but reducing it by the end of the 48
      h observation period. This effect was not dose-dependent in the concentration
      range tested: Lp(a) 450 micrograms/ml; 3 h, 188%; 24 h, 91%; 48 h, 85%; Lp(a) 360
      micrograms/ml: 3 h, 180%; 24 h, 94%; 48 h, 52%). Lp(a) reduced the stimulatory
      effect of cytokines on ET release. Maximal values at 48 h were TNF-alpha 207%,
      TNF-alpha + Lp(a) 91%, IL-1 alpha 212%, IL-1 alpha + Lp(a) 64%. In HPLC analysis,
      the total ET-like immunoreactivity co-eluted with the synthetic human ET
      standard. A cell culture of human brain microvessel endothelial cells was
      established. TNF-alpha and IL-1 alpha increased ET secretion, whereas Lp(a) had a
      dual effect. When given together, Lp(a) reduced the effect of cytokines on ETs.

PMID- 9595486
TI  - Endothelin interactions with brain dopamine systems.
AB  - We examined the interactions of endothelin (ET) with dopaminergic systems in rat
      brain. Using HPLC and radioimmunoassay, we found that striatum contained the
      highest levels of predominantly ET-1, whereas highest levels of predominantly ET
      3 were found in the pituitary. Dopamine depletion in the striatum did not change
      the levels of immunoreactive ET, even though we have previously found a decrease
      in the density of ET receptors. In a comparison of spontaneously hypertensive
      rats (SHR) with Wistar-Kyoto (WKY) rats, ET levels were lower in cerebellum and
      medulla, with no difference in striatum or in other brain areas. In conclusion,
      ET is present in high levels in striatum, but these levels are not affected by
      dopamine depletion or in SHR.

PMID- 9595487
TI  - The significance of endothelin for generation of endocochlear potential.
AB  - The role of intermediate cells (ICs) in the stria vascularis (SV) of the cochlear
      ducts in the generation of endocochlear potential (EP) is clear because certain
      mutants cannot generate EP. Recent reports have shown that endothelin (ET)
      stimulates or inhibits the function of Na+, K(+)-ATPase in various organs. This
      study was designed to examine the immunocytochemical localization of ET and its
      receptor in the SV. The cochlear ducts of WBB6F1 (+/+) mice and mutants (W/Wv)
      devoid of the ICs were used for light and electron microscopic
      immunocytochemistry using rabbit anti-ET-1, ET-3, and ETA receptor antisera. The
      location of Na+, K(+)-ATPase using rabbit anti-rat Na+, K(+)-ATPase was also
      examined. Immunoreactivity to Na+, K(+)-ATPase was seen in the marginal cells
      (MCs) in both species. Immunoreactivity to ET-1 and ET-3 was preferentially
      localized in the rough endoplasmic reticulum and cytoplasmic vesicles of the ICs
      and along the plasma membrane of the ICs and in the MCs apposed to the ICs.
      Immunoreactive sites for ETA were almost identical to those of ET-1 and ET-3.
      Because Na+, K(+)-ATPase activities also exist in the MCs of the mutants, it
      appears likely that ET, synthesized and released by the ICs, may participate in
      generation of EP by regulating the function of Na+, K(+)-ATPase for production of
      the endolymph of the MCs.

PMID- 9595488
TI  - Immunoreactive endothelin levels in the vitreous fluid are decreased in diabetic
      patients with proliferative retinopathy.
AB  - Endothelin (ET) plays an important role in the pathogenesis of various
      cardiovascular lesions. To elucidate the pathophysiologic significance of ET in
      the development of diabetic retinopathy, we determined immunoreactive ET levels
      in the vitreous fluid collected during vitrectomy in seven patients with non
      insulin dependent diabetes mellitus with proliferative diabetic retinopathy and
      in 10 nondiabetic subjects as controls. Immunoreactive vitreous ET levels in
      diabetic patients with proliferative retinopathy (7.5 +/- 3.4 pg/ml, mean +/- SD)
      were significantly lower than those in the nondiabetic subjects (55.0 +/- 38.1
      pg/ml; p < 0.005). The decreased rather than increased immunoreactive ET levels
      may simply reflect severe endothelial injury to the retinal vessels caused by
      diabetic microangiopathy rather than an important role in diabetic retinopathy.

PMID- 9595489
TI  - Endothelin-1 gene expression in blood vessels and kidney of spontaneously
      hypertensive rats (SHR), L-NAME-treated SHR, and renovascular hypertensive rats.
AB  - Spontaneously hypertensive rats (SHR), renovascular hypertensive rats [two-kidney
      one clip Goldblatt (2-K 1C) and 1-K 1C], and SHR treated with the nitric oxide
      (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), do not
      respond to endothelin (ET) receptor antagonists with a decrease in blood
      pressure. However, treatment with ET receptor antagonists has shown some
      beneficial renal and coronary effects in SHR. In this study we examined tissues
      from SHR, L-NAME-treated SHR, 2-K 1C, and 1-K 1C, using in situ hybridization
      with a specific rat preproET-1 cRNA probe to evaluate preproET-1 mRNA abundance
      in blood vessels, heart, and kidneys. Grain density was similar in SHR and Wistar
      Kyoto (WKY) rats in all tissues examined. L-NAME-treated SHR showed increased
      grain density vs. SHR in endothelium of aorta and of small coronary arteries and
      in kidney glomeruli, but not in renal or mesenteric arteries. 2-K 1C presented
      increased grain density in coronary arteries and in glomeruli of the unclipped
      but not the clipped kidney vs. glomeruli of control rats. 1-K 1C rats exhibited
      increases in preproET-1 mRNA relative to unilaterally nephrectomized control rats
      in endothelium of aorta and in mesenteric and coronary arteries, but not in renal
      arteries or glomeruli. None of the hypertensive models studied showed detectable
      evidence of myocardial overexpression of preproET-1 mRNA. Therefore, tissue
      specific enhancement of ET-1 expression may underlie ET-dependent functional
      alterations and may explain the beneficial effects of ET receptor antagonists in
      the coronary circulation or in the kidney in some hypertensive models, but not in
      SHR.

PMID- 9595490
TI  - Coronary arterial lesions in dogs treated with an endothelin receptor antagonist.
AB  - Structurally and pharmacologically diverse vasodilators are known to lower blood
      pressure, increase heart rate, and produce acute injury to right coronary
      arteries in the dog. Administration of low concentrations of endothelin-1 (ET-1)
      to anesthetized dogs causes coronary vasoconstriction and reductions in coronary
      blood flow. Therefore, pharmacologic blockade of endothelin receptors (ETA and
      ETB) with the mixed ET receptor antagonist SB 209670 could lead to coronary
      vasodilatation. In toxicology studies, continuous administration of SB 209670 to
      dogs for 5 days at 50 micrograms/kg/min was associated with minor but sustained
      increases in heart rate (10-30 beats/min), slight decreases in mean arterial
      pressure (10-15 mm Hg), and medial hemorrhage and necrosis of extramural coronary
      arteries in the right atria. Doses of 10 micrograms/kg/min had no effect. The
      lesions in the right atrium were associated with the highest density of ET
      receptors, approximately 470 fmol/mg compared to 170-200 fmol/mg in the
      ventricles and septum. Because changes in systemic cardiovascular parameters are
      minimal, the coronary arterial lesion is most likely due to a local vasodilatory
      effect in the coronary bed.

PMID- 9595491
TI  - Verapamil reduces the arrhythmogenic effect of endothelin.
AB  - In a previous study we established that endothelin-1 (ET-1) can induce
      characteristic ventricular tachycardias (VT) with significant prolongation of QT
      and QTc time. In this investigation we studied the role of CA2+ channels in the
      pro-arrhythmic effects of ET-1. In 24 anesthetized, open-chest mongrel dogs, ET-1
      was administered into the left anterior descending coronary artery at a
      comparatively low dose (60 pmol/min) for 30 min. Twelve dogs received the Ca(2+)
      channel blocker verapamil (0.4 mg/kg) before ET-1 application. The following
      parameters were recorded continuously over the infusion period: systemic arterial
      blood pressure, coronary blood flow, surface ECG leads, epicardial atrial and
      ventricular electrograms, and right and left ventricular endocardial monophasic
      action potentials (MAP). Electrophysiologic studies were performed by programmed
      electrical stimulation of the heart. Blockade of myocardial Ca2+ channels
      attenuated the arrhythmogenic action of ET-1. After verapamil administration to
      ET-1-treated dogs, sustained VT did not appear and ventricular fibrillation (VF)
      developed only in two dogs. In the control group serious and sustained VT and VF
      developed in nine animals. It is noteworthy that verapamil did not prevent ET-1
      induced prolongation of QT time. The results appear to prove that myocardial Ca2+
      channels are involved in the proarrhythmic effect of ET-1.

PMID- 9595492
TI  - Effect of diltiazem and verapamil on endothelin release by cultured human
      coronary smooth-muscle cells and endothelial cells.
AB  - Recent data suggest that endothelin (ET) production is enhanced in coronary
      atherosclerotic lesions. In several studies, an anti-atherosclerotic effect has
      been attributed to calcium-channel antagonists. This study aimed to investigate
      whether ET release from cultured human coronary artery smooth muscle and
      endothelial cells is influenced by the calcium-channel antagonists diltiazem and
      verapamil. Coronary plaque smooth-muscle cells (SMCs) were isolated from primary
      stenosis plaque material. Normal coronary smooth muscle and endothelial cells
      were obtained from organ donors. Addition of diltiazem (5, 15, 25, 50, or 100
      micrograms/ml) and verapamil (0.25, 2.5, 25, 50, or 75 micrograms/ml) to the
      culture medium induced in all three cell types a dose-dependent reduction in ET
      secretion (coronary plaque SMCs: diltiazem 98.1 +/- 1.5, 94.9 +/- 5.0, 82.0 +/-
      6.4**, 63.3 +/- 3.7***, 38.9 +/- 2.4***; control 108.4 +/- 2.8; verapamil 97.0 +/
      7.7, 91.9 +/- 5.5, 67.3 +/- 4.5**, 30.6 +/- 3.0***, 27.6 +/- 2.2***; control
      103.4 +/- 6.1 pg/10(4) cells, n = 6; normal coronary SMCs: diltiazem 9.6 +/- 0.7,
      8.7 +/- 0.6, 5.4 +/- 0.5***; 3.7 +/- 0.5***, 3.2 +/- 0.4***; control 10.7 +/-
      0.5; verapamil 10.3 +/- 0.9, 10.0 +/- 0.7, 6.6 +/- 0.5***, 4.0 +/- 0.3***, 3.0 +/
      0.3***; control 11.1 +/- 0.6 pg/10(4) cells, n = 6; means +/- SEM, **p < 0.01,
      ***p < 0.001 vs. control). These data suggest that ET release from cultured
      coronary smooth muscle and endothelial cells is decreased by diltiazem and
      verapamil. In further studies, it remains to be elucidated whether the local
      application of diltiazem or verapamil might have a beneficial effect on the
      progression of coronary atherosclerosis.

PMID- 9595493
TI  - Endothelin-1 in the heart during exercise.
AB  - In addition to its potent vasocontractile effects, endothelin-1 (ET-1) has potent
      positive inotropic and chronotropic effects on isolated heart muscles in vitro.
      However, it is not known whether the production of ET-1 in the heart is altered
      by exercise. In this study we investigated the production of ET-1 in the heart
      during exercise. Rats performed treadmill running of 45-min duration. Sedentary
      rats served as controls. Immediately after exercise, the heart was quickly
      removed. The peptide level of ET-1 in the heart was measured by a sandwich-enzyme
      immunoassay. The peptide level of ET-1 in the heart was significantly higher in
      the exercise group than in the control sedentary group. Therefore, we have
      demonstrated that production of ET-1 in the heart is increased by exercise. The
      present study suggests that myocardial ET-1 participates in the modulation of
      cardiac function during exercise.

PMID- 9595494
TI  - Gene expression of endothelin-1 and endothelial-type nitric oxide synthase in
      cardiovascular tissues of stroke-prone spontaneously hypertensive rats/Izm:
      effects of the angiotensin-converting enzyme inhibitor aracepril.
AB  - We studied target organ-protective effects of aracepril, an angiotensin
      converting enzyme inhibitor, and the expression of endothelin-1 (ET-1) and nitric
      oxide synthase (NOS) mRNA. Aracepril (30 mg/kg) was administered orally to Izumo
      strain of stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) for 8 weeks
      from 4 weeks of age and for 4 weeks from 8 weeks of age. The expression of ET-1
      and endothelial NOS (eNOS) mRNA in the heart, aorta, kidneys, and brain cortex,
      and the expression of neuronal NOS (bNOS) mRNA in brain cortex, were analyzed by
      RT-PCR/Southern blotting or RNase protection analysis. Administration of
      aracepril markedly lowered blood pressure and decreased left ventricular weight
      in SHR-SP/Izm. Expression of ET-1 mRNA in the heart, kidneys, and brain was
      significantly enhanced in SHR/SP/Izm compared with that in WKY/Izm. Aracepril
      significantly decreased the expression of ET-1 mRNA, whereas there was no
      significant change of that in the aorta. Although expression of eNOS mRNA in the
      heart, aorta, and kidneys did not show any significant difference between the two
      strains of rats, administration of aracepril for 8 weeks significantly decreased
      the expression of eNOS and bNOS mRNA in brain tissue. These results suggested
      that aracepril may protect major target organs by modifying the expression of ET
      1 and NOS mRNA, in addition to its hypotensive effect.

PMID- 9595495
TI  - Characterization of canine pericardial fluid endothelin-1 levels.
AB  - Recently, extremely high concentrations of endothelin-1 (ET-1) were detected in
      the pericardial fluid of patients undergoing cardiac surgery. This study was
      designed to characterize ET-1 levels in plasma and pericardial fluid of dogs.
      Plasma and pericardial fluid samples were extracted using SepPak C18 cartridges
      and ET-1 levels were measured by a specific radioimmunoassay. Pericardial fluid
      ET-1 levels (739 +/- 81 pg/ml; n = 10) were significantly higher than respective
      plasma levels (22.4 +/- 4.0 pg/ml; p < 0.05). The mean pericardial fluid: plasma
      ratio of ir-ET-1 concentration was 54.7 +/- 16.8. In HPLC analysis, the total ET
      1-like immunoreactivity of pericardial fluid co-eluted with ET-1 standard. In
      anesthetized dogs (n = 6), disappearance of [125I]ET-1 was sixfold slower in the
      pericardial space than in plasma. Our results show that high concentrations of ir
      ET-1 can be found in canine pericardial fluid. Slow elimination of ET-1 from the
      pericardial fluid compartment may contribute to high peptide levels.

PMID- 9595496
TI  - Potential pathophysiologic role of endothelin-1 in canine pericardial fluid.
AB  - Recently, extremely high levels of endothelin-1 (ET-1) were detected in the
      pericardial fluid of patients undergoing cardiac surgery. This study was designed
      to assess the pathophysiologic importance of this finding by infusing ET-1 into
      the closed pericardial sac of anesthetized dogs. Systemic arterial blood
      pressure, heart rate, and standard ECG were recorded. Intrapericardial infusion
      of ET-1 (11 and 33 pmol/kg/min; n = 4/4) for 40 min induced ventricular
      arrhythmias in all instances. The lower dose of ET-1 induced a substantial number
      of ventricular extrasystoles, couplets, and triplets. In one instance,
      ventricular extrasystoles accelerated into nonsustained ventricular tachycardia
      (VT). In animals receiving the higher dose, nonsustained VTs occurred regularly,
      whereas sustained VTs were detected in two of four animals. Before the onset of
      arrhythmias, QT time was significantly prolonged [ET-1 (11 pmol/kg/min) 180 +/-
      12 to 198 +/- 10 ms, p < 0.05; ET-1 (33 pmol/kg/min) 192 +/- 15 to 233 +/- 13 ms,
      p < 0.01]. Hemodynamic variables did not change significantly before the onset of
      ventricular arrhythmias. Our results show that administration of exogenous ET-1
      into the pericardial space induces ventricular arrhythmias associated with
      prolongation of QT time.

PMID- 9595497
TI  - Interaction of the renin-angiotensin system and the endothelin system in cardiac
      hypertrophy.
AB  - It has been suggested that the renin-angiotensin system (RAS) interacts with the
      endothelin system in the pathogenesis of cardiac remodeling. We examined
      endothelin system regulation in a model of chronic RAS dysfunction, which is
      believed to be an important factor in cardiac remodeling. We used the transgenic
      rat line TGR(mRen2)27, which overexpresses the mouse Renin-2 gene and shows
      hypertension and left ventricular hypertrophy compared to Sprague-Dawley (SD)
      rats. Ren-2 rats (n = 24) received either losartan (LOS), quniapril (QIN), or
      carvedilol (CARV) for 11 weeks, or no treatment. After 11 weeks left (LV) and
      right ventricular (RV) weights were determined and total RNA extracted. Ren-2
      rats showed a mean systolic blood pressure of 190 mm (+/- SEM), which could be
      normalized to 110 +/- mm (+/- SEM) by treatment with LOS or QIN. CARV also
      reduced blood pressure but did not normalize it. LV end-diastolic pressure was
      normal in both SD and Ren-2 rats. LV weight was increased in the Ren-2 rats
      compared to SD rats, and was significantly reduced to normal in the LOS and QIN
      but not in the CARV group. RV weight was normal in all groups. Northern blot
      analysis of preproendothelin-1 (preproET-1) and endothelin-converting enzyme-1
      (ECE-1) expression revealed a significant (p < 0.05) 20% decrease in preproET-1
      mRNA in the mRen2 rats in the RV and in the LV, compared to SD rats. ECE-1 mRNA
      was unchanged. Treatment with LOS, but not with QIN or CARV, induced preproET-1
      transcription by threefold (p < 0.01) over baseline in both the LV and RV. ECE-1
      mRNA was unaltered in the CARV and LOS group and was decreased by 20% in the QIN
      group. Similar changes in LV and RV indicated a direct influence of a
      dysregulated RAS on the endothelin system. In conclusion, the activated RAS
      downregulates the endothelin system in this model of cardiac hypertrophy. This
      suggests that in chronic RAS activated, the endothelin system may have a
      different pathophysiologic impact as a co-factor leading to cardiac hypertrophy.

PMID- 9595498
TI  - Abnormal neurohumoral responses to exercise in patients with heart disease:
      inhibition of an increase in endothelin-1 production during exercise.
AB  - We have reported that the plasma endothelin-1 (ET-1) level is significantly
      increased by exercise in healthy athletes and that it is elevated in the
      circulation of the non-working leg but not the working leg, suggesting that ET-1
      plays an important role in redistribution of blood during exercise. This study
      was designed to compare alterations of neurohumoral substances by exercise in
      normal subjects and patients with heart disease. Study patients comprised three
      groups: eight patients with congestive heart failure (CHF) due to Ebstein's
      anomaly or single-ventricle heart after Fontan operation; six patients with
      complete transposition of the great arteries (TGA) after an anatomic surgical
      correction who may be candidates for ischemic heart disease; and five age-matched
      normal subjects. All patients were in New York Heart Association functional class
      I. All subjects performed symptom-limited treadmill exercise. It is suggested
      that patients with CHF or TGA have a manifest or latent exercise intolerance,
      respectively. In failed to increase plasma ET-1 level, although it caused a
      greater increase in norepinephrine, angiotensin II, and arginine vasopressin than
      in the controls. Exercise also caused a delay in the increased response of plasma
      ET-1 levels in patients with TGA after an anatomic surgical repair. On the other
      hand, plasma brain natriuretic peptide (BNP) level was augmented by exercise in
      patients with CHF and patients with TGA but not in the controls. The present
      results suggest that an increase in ET-1 production during exercise is absent in
      patients with heart disease. The mechanisms of inhibition of ET-1 production
      during exercise in patients with heart disease remain to be elucidated. However,
      the present study suggests that ET-1 plays an important role in redistribution of
      blood during exercise, and proposes the possibility that failure of an increase
      in ET-1 production results in exercise intolerance in patients with heart
      disease.

PMID- 9595499
TI  - Endothelin-1 expression in hearts of transgenic hypertensive mice overexpressing
      angiotensin II.
AB  - Cardiac myocytes and vascular endothelial cells produce endothelin (ET)-1, which
      has potent hypertrophic effects on cardiac myocytes. Although in cultured
      cardiomyocytes, angiotensin II (Ang II) was reported to enhance ET-1 production
      in vitro, it is not known whether ET-1 production is enhanced by Ang II in vivo.
      We investigated the production and pathophysiologic roles of ET-1 in 20-week-old
      male transgenic hypertensive mice (THM), in which the renin-angiotensin system
      (RAS) was markedly activated because of the presence of both human renin and
      angiotensinogen genes. Systolic blood pressure and the ratio of left ventricular
      weight to body weight were significantly higher in the THM than in control mice,
      indicating that THM developed cardiac hypertrophy. ET-1 production was
      significantly increased in the heart of THM because both ET-1 mRNA expression and
      peptide levels were significantly higher than in controls. However, circulating
      plasma ET-1 levels did not differ between the groups, and blood pressure did not
      change after i.v. injection with a high dose (3 mg/kg) of the ETA/B-nonselective
      receptor antagonist SB209670. These findings suggest that increased cardiac ET-1
      production may contribute to the progression of cardiac hypertrophy and that
      endogenous ET-1 may not be involved in the short-term modulation of blood
      pressure in THM of this age.

PMID- 9595501
TI  - Expression of endothelin-1 and endothelin-converting enzyme-1 mRNAs and proteins
      in failing human hearts.
AB  - Accumulating evidence suggests that endogenous endothelin-1 (ET-1) may contribute
      to the development of heart failure. In this study we determined sites of ET-1
      synthesis and production in the failing human myocardium by immunohistochemistry
      and in situ hybridization for ET-1 and endothelin-converting enzyme-1 (ECE-1).
      Myocardial tissues were obtained from 19 patients with heart failure and from
      four noncardiac patients as controls. In both failing and nonfailing hearts,
      apparent immunoreactivity for ET-1 and ECE-1 was consistently seen in cardiac
      myocytes. Endothelial cells of intramyocardial coronary arteries and veins had
      only weak or focal ET-1 and apparent ECE-1 immunoreactivities. On the other hand,
      in situ hybridization showed strong signals for ET-1 and ECE-1 mRNAs in vascular
      endothelial cells but a lesser intensity of signals in cardiac myocytes. Apparent
      immunoreactivity and strong hybridization signals for both ET-1 and ECE-1 were
      seen in macrophages, which were abundant in infarcted regions of ischemic
      cardiomyopathy and in myocardium of septic patients but were rare in healthy
      hearts. These results suggest that, in failing human heart, vascular endothelial
      cells and macrophages rather than cardiac myocytes appear to be the principal ET
      1 synthetic sites, although ET-1 peptides are abundantly present in cardiac
      myocytes of both failing and nonfailing hearts. Endogenous ET-1 may play a
      pathophysiologic role in human heart failure.

PMID- 9595500
TI  - Endothelin-converting enzyme and angiotensin-converting enzyme in failing hearts
      of rats with myocardial infarction.
AB  - We have previously reported that production of endothelin (ET)-1 is markedly
      increased in failing hearts of rats with chronic heart failure (CHF). It was also
      reported that the production of angiotensin II (Ang II) is increased in the
      failing heart. In this study we investigated both converting enzymes of the ET-1
      system and the angiotensin system. We used left coronary artery-ligated rats as a
      model of CHF. The peptide level of ET-1 in the left ventricle (LV) was markedly
      higher in CHF rats than in control rats. In the LV, expression of preproET-1 mRNA
      was also markedly higher in CHF rats than in controls. The expression of
      endothelin-converting enzyme (ECE)-1 mRNA in the rats with CHF was similar to
      that in controls. Therefore, we believed that the increase in ET-1 production in
      the failing heart originated from an increase in preproET-1 production rather
      than increase in ECE. The expression of angiotensin-converting enzyme (ACE) mRNA
      in failing hearts of CHF rats was significantly higher than that of the sham
      operated rats. The expression of angiotensinogen mRNA in failing hearts of these
      CHF rats was slightly higher than that of the sham-operated rats. This study
      suggests that there is a difference in the role of peptide synthesis between the
      ECE system and the ACE system in rats with CHF.

PMID- 9595502
TI  - Increased cardiac and pulmonary endothelin-1 mRNA expression in canine pacing
      induced heart failure.
AB  - The canine model of pacing-induced heart failure (HF) simulates human dilated
      cardiomyopathy and is characterized by severe hemodynamic perturbations. We have
      previously demonstrated increased plasma endothelin-1 (ET-1) and left ventricular
      (LV) tissue peptide levels in this model. However, the gene expression of ET-1
      has not been studied. Accordingly, we compared preproET-1 mRNA in the lungs and
      LV in control normal dogs, dogs with severe HF after 3 weeks of rapid pacing
      (pHF), and pHF dogs chronically treated with an ETA antagonist, LU135252 (pHF
      LU). PreproET-1 mRNA expression was determined by ribonuclease protection assay
      and quantified by densitometry. In paced dogs, mean pulmonary artery pressure
      (PA) and LV end-diastolic pressure (LVEDP) increased markedly from 16 +/- 4 and 8
      +/- 3 mm Hg, respectively, at baseline to 40 +/- 11 and 34 +/- 7 mm Hg,
      respectively, at 3 weeks (both p < 0.001). Treatment with LU135252 attenuated the
      increase in PA and LVEDP by 30% and 19%, respectively (p < 0.05 for both).
      Compared to controls, preproET-1 mRNA expression in the LV and lungs was markedly
      increased in pHF. This was not changed in the LV but was reduced in the lungs by
      treatment with the ETA antagonist. Increased pulmonary and LV expression of
      preproET-1 suggests that ET-1 plays a role in mediating the pulmonary
      hypertension and LV dysfunction characteristic of this model.

PMID- 9595503
TI  - Modulation of endothelin-1 release by a transmissible factor from ischemic
      myocardium.
AB  - The aim of this study was to detect the possible release from the ischemic rabbit
      myocardium of a factor capable of modulating the release of endothelin-1 (ET-1)
      from the peripheral vasculature. Isolated rabbit hearts were perfused on a
      Langendorff apparatus so that part of the coronary effluent was pumped directly
      into the arterial supply of isolated ears. Mean ET-1 outflow from ears perfused
      with fresh Krebs was 4.33 +/- 0.72 pg/min; from ears perfused with coronary
      effluent it was 84.3% less. This still represented net ET-1 production in the ear
      (venous/arterial ET-1 concentration ratio (V/A) = 3.9 +/- 1.2). Myocardial
      ischemia (30 min) caused a large reduction in ET-1 outflow from the ears and
      changed net production to net loss (V/A = 0.32 +/- 0.17). Within 2 min of
      reperfusion the V/A had risen to 6.3 +/- 2.2 and the ET-1 outflow from the ears
      rose 16-fold. Neither 30-min coronary occlusion nor 2-min reperfusion altered ET
      1 concentrations in the coronary effluents. After 60-min reperfusion, ET-1
      concentration in coronary effluent rose by 230%. During myocardial ischemia and
      reperfusion there was no change in pO2, pCO2 or pH in the perfusate supplying the
      ears. Therefore the changes in ET-1 handling by the ear vasculature must have
      been induced by a transmissible factor released from the heart.

PMID- 9595504
TI  - Bradycardia increases the arrhythmogenic effect of endothelin.
AB  - The effect of permanent bradycardia on the proarrhythmic action of endothelin-1
      (ET) was investigated in 24 open-chest anesthetized mongrel dogs. In 12 dogs,
      permanent bradycardia was induced by radiofrequency ablation of the AV node and
      the hearts were paced at 70 beats/min. ET (60 pmol/min) was infused into the left
      anterior descending coronary artery. Blood pressure, coronary blood flow (CBF),
      and atrial and ventricular epicardial surface ECG were recorded continuously.
      Polymorphous ventricular tachycardia developed in every dog with permanent
      bradycardia, and ventricular fibrillation terminated the experiments in 11 cases.
      Bradycardia prolonged the basal QT but there was no difference in the frequency
      corrected QTc time between the two groups. ET prolonged the QT time in a similar
      fashion in both groups. In the control group, six dogs developed sustained
      ventricular tachycardias and ventricular fibrillation occurred in nine cases.
      EADP was found in six cases of eight registered. Signs of myocardial ischemia did
      not accompany the development of arrhythmias. We conclude that permanent
      bradycardia augments the direct proarrhythmic effect of ET in dogs.

PMID- 9595505
TI  - Increased monophasic action potential dispersion in endothelin-1-induced
      ventricular arrhythmias.
AB  - The aim of this study was to investigate the changes in monophasic action
      potentials (MAP) from different sites in the heart and to determine MAP
      dispersion during endothelin-1 (ET-1) infusion. Standard ECG, left ventricular
      anterior, right ventricular lateral, right ventricular septal, and right
      ventricular apical MAPs and intra-arterial blood pressure were monitored in seven
      anesthetized open-chest mongrel dogs. After radiofrequency atrioventricular node
      ablation, ventricular pacing (70/min) was performed and intracoronary ET-1 (60
      pmol/min) was administered into the left anterior descending coronary artery.
      Both MAPd90 and MAPd90 dispersion increased significant during ET-1 infusion. The
      onset of spontaneous monomorphic and polymorphic sustained ventricular
      tachycardias (sVT) was observed in five dogs (around 40 min), and nonsustained
      VTs (nsVT) developed in another two dogs. The increases in MAP and MAP dispersion
      lasted until the appearance of polymorphic nsVTs and sVTs, but at the time of
      these VTs this difference decreased. At the termination of the experiments,
      ventricular fibrillation occurred in six cases. In four cases third-phase early
      afterdepolarizations were recorded. Our results suggest that increased MAP
      dispersion and development of EAD contribute to the arrhythmogenic action of ET
      1, and these phenomena might explain the pathogenesis of a wide variety of
      ventricular arrhythmias with different morphology observed in this study.

PMID- 9595506
TI  - Mechanism of endothelin-induced malignant ventricular arrhythmias in dogs.
AB  - The development of ventricular tachyarrhythmias caused by low-dose intracoronary
      infusion of endothelin-1 (ET-1) has recently been observed in dogs. The aim of
      the present study was to investigate the pathomechanism of ET-1-induced
      ventricular arrhythmias in 32 anesthetized, open-chest mongrel dogs in group A (n
      = 14) without, in group B (n = 14), and in group C (n = 4 control) with
      atrioventricular node ablation. The coronary blood flow (CBF) was measured in the
      left anterior descending (LAD) coronary artery by an electromagnetic flowmeter.
      Standard ECG, atrial and ventricular electrograms, and in groups B and C
      endocardial and epicardial monophasic action potentials (MAPs) were recorded. ET
      1 was administered into the LAD at a low dose (30-60 pmol/min). At the time of
      the appearance of premature beats, CBF was only slightly decreased. The effective
      ventricular refractory period did not change significantly. Onset of spontaneous
      polymorphic and monomorphic sustained ventricular tachycardia (sVT) was observed
      in five dogs without bradycardia and in nine dogs with bradycardia. VTs in dogs
      with complete AV block were longer and slower. In most of the cases, ventricular
      fibrillation occurred. ET-1 treatment resulted in a significant increase in MAP
      90% duration (255 +/- 9 vs. 290 +/- 8 ms endocardial, 244 +/- 10 vs. 292 +/- 12
      epicardial; p < 0.05) at 70 beats/min ventricular pacing. In eight cases (group
      B), third-phase early afterdepolarization could be recorded. According to our
      results, the mechanism of ET-1-induced arrhythmias appears to be based on
      prolongation of MAP duration and development of afterdepolarizations.

PMID- 9595507
TI  - Endothelin-1 inhibits pacemaker currents in rabbit SA node cells.
AB  - Our recent study demonstrated that endothelin-1 (ET-1) inhibits the pacemaker
      activity of sinoatrial (SA) node cells via changes in the L-type Ca2+, delayed
      K+, and background K+ currents. Using the whole-cell patch-clamp technique in the
      same preparation, we found that ET-1 reduces other pacemaker currents, the T-type
      Ca2+ current (ICa,T) and the hyperpolarization-activated inward current (I(f)).
      The inhibitory actions of ET-1 on these currents were concentration-dependent,
      i.e., EC50 of 0.9 nM for ICa,T and 2.3 nM for I(f), with little reversal after
      washout of the peptide. In the presence of BQ485, both currents were not affected
      by ET-1. These results indicate additional mechanisms underlying negative
      chronotropic actions of ET-1 on the rabbit SA node.

PMID- 9595508
TI  - A nonradioactive method for localization of endothelin receptor mRNA in situ.
AB  - To investigate relationships between the distribution of endothelin (ET) receptor
      expression and histopathology of heart and blood vessels, we developed a method
      of nonradioactive in situ hybridization in paraffin sections. Rat mesenteric bed,
      rat heart, and human uterine artery were fixed in formalin and embedded in
      paraffin ETA and ETB receptor cDNAs were subcloned into plasmid vectors for
      synthesis of sense and anti-sense probes. Digoxigenin (DIG)-UTP was incorporated
      into every twentieth to twenty-fifth nucleotide of the newly transcribed cRNA.
      mRNA was detected in situ using an anti-DIG alkaline phosphatase antibody and an
      alkaline phosphatase substrate. In blood vessels, ETA receptor mRNA was localized
      to the medial smooth muscle layer and ETB receptor mRNA to the endothelial and
      adventitial layers. Hearts from rats that had undergone coronary artery ligation
      for induction of CHF showed intense staining for ETB receptor mRNA in the scarred
      and infarcted zone of the left ventricle. This method provides a suitable
      alternative to radioisotope-labeled probes for detection of ET receptor mRNA. It
      allows better preservation of tissues, shorter detection time, and improved
      morphology for microscopic analysis.

PMID- 9595509
TI  - Selective or nonselective endothelin antagonists in porcine hypoxic pulmonary
      hypertension?
AB  - We evaluated the hemodynamic effects of various endothelin (ET) receptor
      antagonists using selective and non-selective ETA and ETB receptor blockade in
      hypoxic pigs in vivo. BMS-182874 (10 mg/kg i.v.) TBC-11251z (10 mg/kg i.v.),
      selective ETA receptor antagonists, attenuated hypoxia (FiO2 0.1)-evoked increase
      in pulmonary arterial pressure and pulmonary vascular resistance. Bosentan (10
      mg/kg i.v.) a non-selective ETA and ETB receptor antagonist, cause essentially
      similar effects as ETA antagonism alone. No effects were observed after selective
      ETB blockade using BQ-788 (total dose 1 mg i.v.). The vasoconstrictor effect of
      exogenous ET was most effectively antagonized by TBC-11251z, followed by BMS
      182874 and bosentan. The pulmonary vasodilator effect exerted by exogenous ET
      during hypoxia was reversed by BQ-788 and bosentan but not by TBC-11251z or BMS
      182874. We can therefore conclude that ET contributes to hypoxic pulmonary
      vasoconstriction primarily through ETA receptor activation.

PMID- 9595510
TI  - Chronic hypoxia-induced cardiopulmonary changes in three rat strains: inhibition
      by the endothelin receptor antagonist SB 217242.
AB  - The cardiopulmonary profile of three different rat strains was compared after
      exposure to hypoxia (9% O2) for 0, 7, or 14 days. In Sprague-Dawley (SD), Wistar
      (W), and high altitude-sensitive (HAS) rats, pulmonary arterial pressure (PAP)
      rose 30, 58, and 85% respectively, after 7 days of hypoxia, and by 108, 116, and
      167%, respectively, at 14 days compared to strain- and age-matched normoxic
      controls. Right ventricular hypertrophy (RVH), expressed as the ratio of right
      free wall/left wall + septum weight, in SD, W, and HAS was increased by 24, 53,
      and 48%, respectively, at 7 days, and by 51, 93, and 55% at 14 days compared to
      normoxic littermates. Histologically, marked medial thickening and luminal
      stenosis of small and medium-sized arteries were observed in all hypoxic rats,
      being most pronounced in the HAS rats at 14 days. Treatment of HAS rats with the
      ET receptor antagonist SB 217242 (3.6 or 10.8 mg/day i.p. by osmotic pump)
      significantly inhibited the hypoxia-induced increases in PAP (70-75% decrease).
      RVH was inhibited by 40% at the dose of 10.8 mg/day. Histologically, the SB
      217242-treated rats had almost "normal" small and medium-sized arteries,
      comparable to those of the normoxic HAS controls. This study demonstrates an
      exaggerated PAP response to chronic hypoxia in HAS compared to SD and W rats. The
      inhibitory influence of SB 217242 on the functional and morphologic changes
      induced by hypoxia provides further evidence for a role for ET and the potential
      utility of ET receptor antagonists in the treatment of pulmonary hypertension.

PMID- 9595511
TI  - Effects of tetramethylpyrazine, a Chinese medicine, on plasma endothelin-1 levels
      during acute pulmonary hypoxia in anesthetized dogs.
AB  - Our study was designed to elucidate the effects of tetramethylpyrazine (TMP), a
      Chinese medicine, on plasma endothelin-1 (ET-1) levels in dogs with acute
      pulmonary alveolar hypoxia. Anesthetized dogs were used under artificial
      ventilation with room air or a hypoxic gas mixture (10% O2 and 90% N2) (n = 10)
      for 60 min. Effects of TMP (80 mg/kg) were studied by i.v. injection of TMP
      before exposure to hypoxia (n = 8). Mean pulmonary arterial pressure (PAPm),
      systemic arterial pressure (SAPm), right atrial pressure (RAP), pulmonary
      capillary wedge pressure (PCWP), cardiac output (CO), and heart rate (HR) were
      measured. The pulmonary vascular resistance (PVR) was calculated by the equation
      of (PAPm-PCWP) x 8/CO. Plasma ET-1 levels were determined in the abdominal aorta
      and pulmonary artery by RIA. The effects of TMP on PAP and plasma ET-1 level were
      evaluated by using percent increase in PAPm and the change of Da-pET (delta ET)
      before and after hypoxia. Both PAPm and PVR were significantly elevated 5 min
      after acute hypoxia over a period of 60 min, whereas CO and PCWP did not change.
      Plasma ET-1 levels in the abdominal aorta and Da-pET showed a significant
      increase. Administration of TMP significantly decreased the hypoxia-induced
      increase in the PAPm, PVR, and delta ET. These results suggest that TMP could be
      a useful therapeutic agent in the treatment of pulmonary hypertension induced by
      acute hypoxia through decrease of plasma ET-1 levels.

PMID- 9595512
TI  - Heparin suppresses cyclosporine-induced endothelin-1 synthesis in rat endothelial
      cells.
AB  - Cyclosporine stimulates vasoconstrictor endothelin-1 (ET-1) synthesis. This study
      examined the effect of heparin on cyclosporine-induced ET-1 synthesis in Wistar
      rat aortic endothelial cells in culture. Cyclosporine (0.01-5 mumol/L) stimulated
      ET-1 mRNA expression in a dose-dependent manner. A nitric oxide synthesis
      inhibitor, NG-monomethyl-L-arginine (L-NMMA) (10(-5) mol/L), did not affect
      cyclosporine-induced ET-1 mRNA expression. Heparin (1-20 U/ml) suppressed
      cyclosporine-induced ET-1 mRNA expression in a dose-dependent manner. The
      inhibitory effect of heparin was blunted in the presence of either L-NMMA (10(-5)
      mol/L) or calmodulin inhibitors such as N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide (W-7) (5 x 10(-5) mol/L) or calmidazolium (5 x 10(-5)
      mol/L) in the presence of the phosphodiesterase inhibitor 3-isobutyl 1
      methylxanthine (0.1 mmol/L). These results suggest that heparin suppresses
      cyclosporine-induced ET-1 mRNA expression via both NO- and calmodulin-dependent
      pathways.

PMID- 9595513
TI  - Transcriptional regulation of endothelin-1 by erythropoietin in endothelial
      cells.
AB  - Recombinant human erythropoietin (rHuEpo) has been widely used in patients
      undergoing chronic hemodialysis treatment to correct anemia. In a subgroup of
      patients, i.v. administration of rHuEpo leads to manifestation or worsening of
      hypertension. The underlying mechanism of this remains unclear but it has been
      suggested that it is associated with increased expression of the vasoconstrictor
      endothelin (ET) in endothelial cells (ECs). There is also evidence for expression
      of specific rHuEpo receptors on ECs. The aim of this work was to study the time
      course and mechanisms of ET-1 regulation on the mRNA level in bovine aortic
      endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs)
      stimulated with pharmacologic doses of rHuEpo (1-10 IU/ml). Compared to vehicle
      treated controls, rHuEpo-treatment of ECs increases preproET-1 mRNA expression up
      to 170%, as shown by Northern blotting. To study the transcriptional regulation
      of ET-1 expression by rHuEpo, ECs were transfected with a luciferase construct
      driven by the rat ET-1 promoter and subsequently stimulated with rHuEpo. Compared
      to controls, luciferase activity increased up to 200% (n = 6; p < 0.05),
      suggesting transcriptional regulation of preproET-1 mRNA-expression by rHuEpo.
      Our data support the hypothesis that ET contributes to the hypertensive side
      effects of rHuEpo treatment and that this interaction occurs at the
      transcriptional level.

PMID- 9595514
TI  - Suppression of endothelin-3-induced nitric oxide synthesis by triglyceride in
      human endothelial cells.
AB  - Reduced endothelium-derived nitric oxide (NO) production characterizes several
      vascular diseases. This study examined the effect of triglyceride on NO
      production induced by endothelin-3 (ET-3) in cultured human umbilical vein
      endothelial cells. Triglyceride-rich human plasma obtained after a high
      carbohydrate diet with white wine was used in an ex vivo study. The plasma
      triglyceride fraction was found to consist of large amounts of palmitic and oleic
      acids detected by gas-liquid chromatography. Therefore, the effect of synthetic
      tripalmitin and triolein emulsion on NO production was also examined. ET-3
      stimulated NO and guanosine 3',5'-cyclic monophosphate production and increased
      cytosolic Ca2+ levels in the endothelial cells (ECs). After incubation of the ECs
      with the triglyceride-rich plasma for 2 h, these responses to ET-3 were
      ameliorated in a triglyceride concentration-dependent manner (50-200 mg/dl). A
      synthesized emulsion of tripalmitin (100 mg/dl) and triolein (100 mg/dl) also
      blunted the responses to ET-3. Neither endothelial constitutive NO synthase mRNA
      expression nor its protein level was affected by treatment with triglycerides.
      These results suggest that triglyceride suppresses ET-3-induced NO synthesis in
      human ECs by inhibiting cytosolic Ca2+ elevation.

PMID- 9595515
TI  - Role of endothelin in thrombolysis in rat abdominal aorta.
AB  - The endothelium of blood vessels is of great importance in maintaining blood
      fluidity and modulating thrombogenesis. Endothelin (ET) participates in
      thrombogenesis and its role in the pathogenesis of heart diseases such as acute
      myocardinal infarction has been proved, but little is known about the effect of
      ET on thrombolysis. Using a model of thrombosis in rat abdominal aorta induced by
      direct current-ferric trichloride, we found that the plasma ET level was 3.7
      times the baseline after lysing the thrombus with urokinase (250,000 U/kg) while
      5 micrograms/kg of exogenous ET prolonged the time of thrombolysis to 115% of
      baseline control. Plasma ET level was six times the baseline level. Incubation of
      a rat aortic strip in vitro with taurine (20 mmol/L) had no effect on baseline ET
      release, but taurine prohibited the stimulation of thrombin and A23187 of ET
      release in a dose-dependent way. Plasma ET decreased between 17 and 40% after
      injection of taurine, which also decreased by 45% the time of lysis of thrombus.
      From the above data it might be concluded that ET inhibits thrombolysis and that
      the abnormally increasing plasma ET can be attenuated by taurine, which is
      beneficial to thrombolysis.

PMID- 9595516
TI  - Functional studies in small arteries do not support a primary role for endothelin
      in the pathogenesis of Raynaud's disease.
AB  - Endothelin-1 (ET-1) has been implicated in the pathogenesis of Raynaud's disease
      (RD). This study examined the effect of cooling on the response to ET-1 in human
      microvessels. Subcutaneous small arteries were dissected from gluteal fat
      biopsies taken from patients with RD (n = 20) and from age- and sex-matched
      control subjects (n = 17) and were cannulated in a small vessel arteriograph.
      Cumulative concentration-response curves to ET-1 (10(-12) to 3 x 10(-7) M) were
      obtained in vessels at 37 degrees C and 24 degrees C, with the endothelium either
      intact or removed (n = 6 per group). There were no significant differences in
      responses to ET-1 between RD patients and controls in either intact or denuded
      vessels, at either 37 degrees C or at 24 degrees C. There was, however, a
      significant endothelium-dependent interaction between the groups when the effect
      of temperature on the response to ET-1 was examined (p = 0.01; two-way ANOVA).
      Whereas cooling tended to reduce the sensitivity in RD, the opposite effect was
      observed in controls. Measurements of plasma ET-1 did not reveal any significant
      difference between patients with RD and healthy controls. These results suggest
      that ET-1 does not play a primary pathophysiologic role in RD. ET-1 might be
      responsible for mediating the prolonged vasospasm in RD, but secondary to another
      factor(s), such as impaired endothelium-dependent vasodilation.

PMID- 9595517
TI  - Changes in endothelin-1, 6-keto-PG-F1 alpha, and TX-B2 in random pattern flaps.
AB  - In this study we investigated kinetic changes in the ratio of endothelin-1 (ET-1)
      and eicosanoids (6-keto-PG-F1 alpha TX-B2) in 20 x 60 mm random pattern flaps
      from rats. The ET-1 content of regions A (20 mm from the peripheral end) and B
      (20-40 mm) 6 h after surgery tended to decrease slightly compared to the ET-1
      content immediately after surgery. The ET-1 content of region C (20 mm from the
      flap base) 6 h postoperatively increased significantly compared to that
      immediately after surgery. The ET-1 content of region C 6 h after surgery was
      significantly higher compared to that of regions A and B, which were obtained
      simultaneously. The ratios of eicosanoids in the three regions 6 h after surgery
      were significantly lower than those immediately after operation. However, the
      ratio in region A was higher than that in region C, showing that there was a
      difference in distribution in the flap between ET-1 and eicosanoids. The
      administration of an ETA receptor antagonist, FR-139317, extended the survival
      length of the flap. These results suggest that ET-1 can regulate the
      microcirculation in a flap directly and/or indirectly.

PMID- 9595518
TI  - Endothelin in liver cell injury and regeneration after 70% hepatectomy with
      portal ischemia.
AB  - Hepatic ischemia-reperfusion (IR) injury caused by portal vein clamping is a
      common problem in hepatobiliary surgery. Endothelin (ET) is a potent
      vasoconstrictor and is associated with IR injury. This study evaluated the effect
      of ET on liver cell injury and hepatic regeneration after hepatectomy with IR.
      The portal veins of rats were clamped for 20 min, then unclamped and a 70%
      partial hepatectomy was performed. TAK-044 (TAK), the nonselective ETA/ETB
      receptor antagonist, was administered s.c. 30 min before laparotomy [TAK(+)].
      Portal blood ET-1, GOT levels, hepatic blood flow, histologic change, DNA
      synthesis of hepatocytes, and the relationship of Ito cells and perisinusoidal
      cells were evaluated. ET-1 concentration increased after IR and was significantly
      higher in the TAK(+) group owing to the blockade of ET receptors. Increased GOT
      levels and sinusoidal congestion were reduced, but DNA synthesis of hepatocytes
      and hepatic blood flow did not change in the TAK(+) group. Changes in desmin
      staining showed that Ito cells might be related to IR injury. In conclusion, ET-1
      was associated with IR injury and TAK-044 reduced but did not affect hepatocyte
      DNA synthesis after partial hepatectomy.

PMID- 9595519
TI  - Endothelin-1 and endothelin-3 levels in different types of glomerulonephritis.
AB  - There is evidence that an activated renal endothelin (ET) system is involved in
      development of glomerulosclerosis. However it is still unknown if different ETs
      are involved in the pathogenesis of various types of glomerulonephritis (GN).
      This study characterized ET-1 and ET-3 levels in patients suffering from chronic
      GN. We performed a prospective study to evaluate the ET-1 and ET-3 levels in 19
      patients with biopsy-proven GN, including four minimal-change nephropathies
      (MCN), six perimembraneous GN (PM-GN), and nine mesangioproliferative GN (MP-GN).
      Twelve healthy subjects matched for age and sex served as controls. ET-1 and ET-3
      were measured in plasma (p) and in urine [spontaneous urine (sp.urine) and urine
      over 24 h (24-h urine)] using a specific radioimmunoassay. Patients and controls
      were compared using the Wilcoxon rank-sum test. In MCN, ET-1 levels were enhanced
      in sp. urine (p = 0.03) and 24-h urine (p = 0.01), whereas ET-3 levels did not
      differ from controls. In comparison, in PM-GN we found an increased ET-3 level in
      24-h urine (p = 0.004). In MP-GN, ET-3 levels were also elevated in p (p =
      0.0002) and urine specimens (sp. urine p = 0.05; 24-h urine p = 0.03). No
      positive correlation to C3 or C4 complement fractions was found. Age, blood
      pressure or renal function did not correlate with ET-1 or ET-3 levels. In MP-GN
      and PM-GN, ET-3 is elevated whereas ET-1 is not. In contrast ET-1 is increased in
      MC-GN. These data indicate an important role for the ET-1 and ET-3 systems in the
      pathophysiology of different forms of GN. This is significant with regard to an
      early preservation of renal function at the onset of GN by the use of selective
      ET antagonists.

PMID- 9595520
TI  - Chronic effects of FR139317 and enalapril on renal failure rats with moderate
      exercise.
AB  - We assessed the renal effects of moderate treadmill exercise in the spontaneously
      hypertensive rats (SHR) remnant kidney model of chronic renal failure (CRF). The
      effects of chronic administration of a specific endothelin (ET) subtype A (ETA)
      receptor antagonist, FR139317 (32 mg/kg/day i.p.) and an angiotensin-converting
      enzyme inhibitor, enalapril (2 mg/kg/day i.p.), in combination with moderate
      exercise were also investigated. Eight-week-old SHR were subjected to 5/6
      nephrectomy. One week after surgery the rats were divided into five groups: (a)
      no treadmill running; (b) moderate treadmill running, 20 m/min for 60 min (Ex)
      per day; (c) Ex plus FR139317; (d) Ex plus enalapril; and (e) m-Ex plus enalapril
      in combination with FR139317, for 4 weeks. In SHR-CRF, Ex significantly
      attenuated the increase in urinary protein excretion. Enalapril significantly
      attenuated the increase in systolic blood pressure and urinary protein excretion.
      FR139317 at this dose did not show any antihypertensive or renal protective
      effect in this model. These results suggest that moderate exercise may protect
      renal function in SHR CRF. They also suggest that FR139317 may not have an
      additional antihypertensive and renal protective effect in this exercise model.

PMID- 9595521
TI  - Pathophysiology in endothelin-1 transgenic mice.
AB  - Transgenic mice expressing the human endothelin-1 (ET-1) were generated. These
      mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not
      hypertension. Consequently, a progressive decrease in renal blood flow and/or
      glomerular filtration rate was observed, demonstrated by altered creatinine
      clearance and by magnetic resonance imaging. These genetically altered transgenic
      mice provide an interesting animal model in which to elucidate the role of ET-1
      in the modulation of renal hemodynamics and glomerular and tubule functions.

PMID- 9595522
TI  - Renal endothelin system in diabetes: comparison of angiotensin-converting enzyme
      inhibition and endothelin-A antagonism.
AB  - An activated renal endothelin (ET) system is implicated in the pathogenesis of
      renal fibrosis, as recently shown in ET-1 transgenic mice. Because progressive
      renal fibrosis is also a major finding in diabetic nephropathy, we analyzed the
      activity of the renal ET system in rats with streptozotocin-induced diabetes
      mellitus and the effect of blocking the ETA receptor, using the orally active ETA
      antagonist LU 135252. The effects of long-term treatment with LU 135252 were
      compared with those of an ACE inhibitor. Plasma and urinary ET-1 concentrations
      were measured. Progression of diabetic nephropathy was analyzed by measuring
      urinary albumin and protein excretion. Urinary ET-1 excretion was significantly
      elevated as early as 7 days after induction of diabetes and increased further.
      The daily urine volume was significantly correlated with urine ET-1 excretion.
      Treatment with LU 135252 significantly decreased the ET-1 excretion by more than
      50%, whereas ACE inhibition resulted only in a mild decrease. Albumin excretion
      was significantly decreased after ACE inhibition, whereas ETA inhibition resulted
      in a nonsignificant decrease. Urinary ET and albumin excretion probably reflect
      independent mechanisms of renal damage in diabetes.

PMID- 9595523
TI  - Is captopril-induced improvement of insulin sensitivity mediated via endothelin?
AB  - Angiotensin-converting enzyme (ACE) inhibitors have been reported to improve
      insulin sensitivity during either short-term or long-term administration. Recent
      studies indicate that endothelin-1 (ET-1) has potent glycogenolytic effects in
      rat hepatocytes and may cause insulin resistance in rat adipocytes. In addition,
      ET may also have a role in stimulation of the hypothalamic-pituitary-adrenal
      axis. To test the hypothesis that part of the effect of captopril in enhancing
      insulin sensitivity may be mediated via ET and/or by glucocorticoids, we measured
      24-h urinary excretion of ET and free cortisol before and after short-term
      treatment with captopril. The 24-h urinary immunoreactive endothelin (IR-ET)
      excretion decreased significantly (p < 0.05) from 65 +/- 4 ng at baseline to 42
      +/- 3 ng after captopril treatment, whereas no significant change in the 24-h
      urinary free cortisol excretion was observed. Moreover, no significant change in
      the 24-h urinary IR-ET and free cortisol excretions was noted in the placebo
      treated group. We speculate that ACE inhibitors may exert their effect on insulin
      sensitivity not only by blocking the renin-angiotensin and kinin systems but also
      by inhibiting production and/or release of ET.

PMID- 9595524
TI  - Signaling mechanisms induced by endothelin agonists in human adrenal glomerulosa
      cells.
AB  - Endothelin-1 (ET-1) exhibits secretagogue and trophic actions on the adrenal zona
      glomerulosa (ZG). Little information is available on the intracellular signaling
      events that follow stimulation of ET receptors on ZG cells. This study examined
      the expression of ET receptor subtypes and their involvement in transduction
      mechanisms induced by ET agonists on human ZG cells in primary culture. RT-PCR
      allowed the detection of both ETA and ETB receptor mRNAs in these cells. ET-1
      induced a concentration-dependent increase in inositol phosphate (IP)
      accumulation in the presence of LiCl, whereas ETB agonists were inactive. The ET
      1-induced increase in IP accumulation was prevented by BQ-123. ET-1 evoked an
      increase in [Ca2+]i, which was partially prevented by BQ-788. IRL 1620 also
      delayed the rise in [Ca2+]i. These results show that in human adrenal ZG cells,
      ET-1 induces an increase in IP accumulation through ETA receptor activation and
      evokes a rise in [Ca2+]i via stimulation of both ETA and ETB receptors.

PMID- 9595525
TI  - The role of receptor-operated CA2+ influx in endothelin-induced contraction of
      the muscularis mucosae.
AB  - We examined the role of receptor-operated Ca2+ influx in endothelin-1 (ET-1)- or
      sarafotoxin S6c (S6c)-induced contraction of the muscularis mucosae. Responses of
      the esophageal muscularis mucosae isolated from guinea-pigs were recorded by an
      isotonic transducer and a polygraph. ET-1 and S6c produced contraction of the
      esophageal muscularis mucosae in a concentration-dependent manner. The
      contractile responses to ETs were abolished in a Ca(2+)-free EGTA-containing
      medium, weakly inhibited by nicardipine, and markedly inhibited by SK&F96365. In
      addition, both H-7 and U-73122 strongly inhibited the ET-induced contractions,
      but U-73343 weakly inhibited these responses. These results indicate that the
      esophageal muscularis mucosae of guinea pigs has ET receptors that are coupled
      mainly to receptor-operated Ca2+ influx and linked with the phospholipase C
      protein kinase C pathway.

PMID- 9595526
TI  - Relationship between recurrence of gastric ulcer and the microcirculation.
AB  - We investigated the relationship between microcirculatory disturbance and the
      host response to Helicobacter pylori infections in gastric ulcer scars to
      determine the role of endothelin-1 (ET) in ulcer recurrence. The subjects were
      divided into three groups. The GuS group consisted of patients who had red
      scarring (S1 stage) at the gastric angle with H. pylori, the gast+ group who had
      gastritis with H. pylori, and the gast- group who had gastritis without H.
      pylori. During endoscopic examination, biopsies were taken from the gastric
      angle. Mucosal ET, nitric oxide (NO), interleukin-8 (IL-8), and RANTES were
      measured. ET, inducible NO synthase (iNOS), and endothelial constitutive NOS
      (ecNOS) were immunostained. Mucosal ET and oxides of nitrogen (NOx) were
      significantly higher in the GuS group than in the other groups. IL-8 was elevated
      in the GuS and gast+ groups, and RANTES was elevated in the gast+ group (p <
      0.01). There was prominent inflammatory cell infiltration in the GuS group. ET
      positive cells were found in vascular smooth muscle, gastric epithelium, and
      gastric smooth muscle. iNOS-positive cells were found in vascular smooth muscle,
      gastric epithelium, gastric smooth muscle, and inflammatory cells. In conclusion,
      local inflammation and microcirculatory disturbance persist at the center of the
      ulcer scar (S1). Decreased cytokine levels and increased ET and NO (mainly
      synthesized by iNOS) levels suggested that microcirculatory disturbance is a more
      important factor than immune response in ulcer recurrence.

PMID- 9595527
TI  - Human bone marrow platelet progenitors express and release endothelin-1.
AB  - Because it has been shown that human platelet precursors from normal bone marrow
      express preproendothelin-1 (ET-1) mRNA, this investigation was designed to find
      out whether these cells could synthesize and release mature ET-1 and express ET
      receptors. Therefore, we examined the expression of endothelin-converting enzyme
      (ECE) mRNA and of mRNAs for ET receptors in cells purified from normal bone
      marrow and measured immunoreactive (ir)ET in their culture medium. RT-PCR applied
      to RNAs from platelet precursors yielded amplified fragments of the expected
      sizes of 567, 428, and 299 bp for ECE, ETB and ETA receptors, respectively. These
      cells released ir-ET into the culture medium in a time-dependent fashion. These
      results raise the possibility of autocrine actions of the intrinsic ET system in
      bone marrow platelet precursor cells.

PMID- 9595528
TI  - Phosphoramidon-sensitive and -insensitive endothelin-converting enzyme in human
      megakaryoblastic cell lines.
AB  - The human megakaryoblastic cell lines HEL, MEG-01, and DAMI express
      preproendothelin-1 mRNA. This investigation was designed to find out whether they
      could also express endothelin-converting enzyme (ECE) and release mature
      endothelin (ET). RT-PCR applied to RNA isolated from the cell lines amplified
      fragments of the expected size. The amplified cDNA of MEG-01 was submitted to
      restriction enzymes, which generated the expected subfragments. Membrane ECE
      activity was phosphoramidon-sensitive, in contrast to the cytosolic activity
      capable of producing ET-1 from big ET-1. The three cell lines produced ir-ET in a
      time-dependent manner. These results show that human megakaryoblastic cell lines
      express functional, phosphoramidon-sensitive and insensitive ECE activity and
      produce mature ET.

PMID- 9595529
TI  - Endothelin-1 selectively potentiates the purinergic component of sympathetic
      neurotransmission in rat seminal vesicle.
AB  - Endothelin-1 (ET-1; 3-100 nM) caused graded tonic contractions and enhanced
      neurogenic contractions in rat field-stimulated seminal vesicle. At 100 nM, ET-1
      increased nerve-mediated responses by 350 +/- 74 mg/100 mg wet tissue (almost
      100% potentiation), whereas sarafotoxin S6c was ineffective. The potentiation of
      neurogenic responses by ET-1 was virtually abolished by the ETA receptor
      antagonist BQ-123 (1 microM; c. 95% inhibition) but was not modified by the ETB
      receptor antagonist BQ-788 (1 microM). Responses to field stimulation were
      inhibited by tetrodotoxin (0.1 microM; 100%), guanethidine (GTD; 5 microM, 75%),
      prazosin (PRA; 0.1 microM, 90%), desensitization of P2x purinoceptors with
      alpha,beta-methylene-ATP (mATP; 10 microM, 50%), or atropine (ATR; 0.1 microM,
      40%). ET-1-induced potentiation of neurogenic contractions was not modified by
      prior incubation with indomethacin (5.6 microM), ATR, or PRA, but mATP and GTD
      reduced the effects of 100 nM ET-1 to 189 +/- 76 and 5 +/- 7 mg/100 mg wet
      tissue, respectively (n = 6-8). Therefore, ET-1 enhances nerve-mediated responses
      of this tissue by selectively potentiating the purinergic component of
      sympathetic neurotransmission. This action, which is independent of the
      eicosanoid-cycloxygenase pathway, is mediated via ETA receptors and, at least in
      part, by enhancement of motor responses to ATP.

PMID- 9595530
TI  - Effects of endothelin-1 on inflammatory incapacitation of the rat knee joint.
AB  - This study assessed the possible local nociceptive and hyperalgesic properties of
      endothelin-1 (ET-1) in the rat knee-joint incapacitation test, in which animals
      are placed for 1 min/h on a revolving (3 rpm) metal cylinder and nociception is
      measured as the time the hindpaw of the injected limb was off the cylinder (i.e.,
      paw elevation time, PET). Carrageenan (Cg; 150 micrograms/joint), E. coli LPS (1
      microgram/joint), and ET-1 (120 or 240 pmol/joint) each increased PET
      persistently, unlike sarafotoxin S6c (120-240 pmol/joint) or PBS. ET-1 (15 and 30
      pmol/joint, 30 min before) did not cause incapacitation per se but potentiated
      PET induced by Cg, increasing the area under the curve (AUC in arbitrary units, 0
      6 h) from 105 +/- 9 to 165 +/- 10 and 169 +/- 25, respectively. Prior Cg
      injection (300 micrograms/joint, 72 h before) sensitized the joint to
      incapacitation triggered by restimulation with either Cg (300 micrograms/joint),
      LPS (1 microgram/joint), or ET-1 (30 pmol/joint). Treatment with bosentan (10
      mg/kg i.v., 15 min before joint stimulation) did not affect PET values in naive
      animals to Cg or LPS, but significantly reduced the upregulated response evoked
      by restimulation with LPS (but not Cg), from 465 +/- 24 to 290 +/- 49 (AUC 0-12
      h). Therefore, ET-1 triggers nociception and hyperalgesia in the naive knee joint
      of the rat, perhaps via ETA receptors. Although local endogenous ETs may not have
      a role in inflammatory nociception in the naive joint, they may participate in
      articular incapacitation induced by restimulation with LPS. This latter finding
      could be relevant to the etiology of pain associated with chronic arthritic
      diseases.

PMID- 9595531
TI  - Endothelins inhibit mineralization of rat calvarial osteoblast-like cells.
AB  - We examined the effects of members of the endothelin (ET) family on
      mineralization of rat calvarial osteoblast-like cells. The accumulation of
      calcium in cells and cell layers was attenuated by ETs with the rank order of
      potency ET-1 = ET-2 > ET-3. We stained the mineralized nodules by von Kossa
      staining and measured the number and area of mineralized nodules. The inhibitory
      effects of ET-1 and ET-2 on the formation of mineralized nodules were stronger
      than those of ET-3. Our data suggest that ET-1 may inhibit the mineralization
      process of osteoblastic cells through the ETA receptor.

PMID- 9595532
TI  - Changes with age and sex in levels of plasma and ovarian or testicular endothelin
      1 in rats.
AB  - Mammalian ovaries and testes contain various intragonadal peptides necessary to
      control gonadal function. Effects of aging and sex on total plasma and ovarian or
      testicular endothelin-1 (ET-1) levels were studied in female and male rats aged 4
      140 days. At 2 weeks, plasma ET-1 levels were 2.69 +/- 0.09 and 2.41 +/- 0.03
      pg/ml (mean +/- SEM; n = 10) in the female and male, respectively. After a
      temporary decrease, mean ET-1 concentrations increased at 10 weeks and again
      decreased at 20 weeks in the female, thereafter revealing a plateau, whereas the
      ET-1 concentrations gradually decreased in the male. In adult females, plasma ET
      1 levels were 3.7-fold higher than male levels. Ovarian ET-1 levels gradually
      increased after birth to 2 weeks, then decreased, and again increased at 3 weeks.
      Thereafter they gradually decreased, showing a plateau after 10 weeks. In
      contrast, testicular ET-1 levels gradually decreased after birth. This difference
      is parallel to but much larger than the sex difference in ovarian or testicular
      ET-1. Gonadal ET-1 showed a very different ontogeny.

PMID- 9595533
TI  - Mechanism of endothelin-1 release from endothelial cells in pregnancy-induced
      hypertension.
AB  - We investigated the mechanism of vasoconstrictor-induced endothelin-1 (ET-1)
      release from human umbilical vein endothelial cells (HUVECs) in serum from women
      with pregnancy-induced hypertension (PIH). We obtained serum samples from seven
      women with PIH, seven healthy nonpregnant women (NP), and seven normal pregnant
      women (NPIH). ET-1 and inositol 1,4,5-trisphosphate (IP3) were assayed by ET-1
      ELISA and an IP3 3H assay system, respectively. ET-1 release from HUVECs
      incubated with 10% serum (NP, NPIH, and PIH) was greater than that without human
      serum. Angiotensin II (Ang II)- and epinephrine (Epi)-induced ET-1 release were
      significantly increased by PIH serum. IP3 production in HUVECs incubated with 10%
      serum (NP, NPIH, and PIH) was greater than that without human serum. Ang II- or
      Epi-induced IP3 production in HUVECs incubated with PIH serum was increased but
      not significantly compared to that with other sera. Our results suggest that
      increased ET-1 release from HUVECs incubated with human serum may be mediated by
      IP3 production, but that Ang II- or Epi-induced ET-1 release from HUVECs
      incubated with PIH serum may be mediated by another mechanism.

PMID- 9595534
TI  - Endothelin receptors and angiotensin II receptors in tumor tissue.
AB  - In cancer chemotherapy, selective enhancement of drug delivery to tumor tissue is
      essentially important for increase of chemotherapeutic effects. An attenuated
      vasoconstrictive response to angiotensin II (Ang II) in tumors and a marked
      increase in tumor blood flow were observed compared with normal tissues during
      systemic hypertension induced by Ang II infusion. The phenomenon was absent when
      hypertension was provoked by endothelin-1 (ET-1). We assessed this response to
      characterize ET receptor and Ang II receptor density and affinity in normal and
      tumor tissues. The tumor cell line LY80 was transplanted to the skin in nude
      rats. Four weeks later the rats were sacrificed. [125I] ET-1 and [125I Sar1,
      Ile8]-Ang II were used to map the receptors for ET and Ang II in rat tissues
      using computerized in vitro autoradiography. A moderately high density of ET
      receptors, (ETB > ETA) was found in tumors. The Ang II receptors were markedly
      reduced in tumor tissues without changes in the affinity. These results suggest
      that the decrease in Ang II receptors but not ET receptors in tumors may explain
      the hemodynamic effect of Ang II-induced hypertension and ET-induced hypertension
      on tumor blood flow.

PMID- 9595536
TI  - The effect of oxygen and carbon dioxide on tumor cell endothelin-1 production.
AB  - Endothelin-1 (ET-1) is produced by some tumor cells, but the dependence of this
      production on pO2 and pCO2, conditions relevant within the tumor
      microenvironment, has not been described. HT29 colon adenocarcinoma cells and
      DU145 prostate carcinoma cells produce similar amounts of ET-1 in vitro under
      normal cell culture conditions of 21% O2/5% CO2 (normoxia). Exposure of HT29
      cells to either 2% O2 or 0.2% O2 significantly reduced ET-1 production compared
      to cells in normoxia. In contrast, production of ET-1 by DU145 cells was usually
      unaffected by hypoxia and was even slightly increased in cells exposed to 2% O2
      in HEPES-buffered EMEM (HEPES-EMEM). Exposure of cells to either 2.2% CO2 or 7.1%
      CO2 had no effect on the production of ET-1 by cells in bicarbonate-buffered EMEM
      (EMEM). However, in HEPES-EMEM, ET-1 production by both cell lines was reduced in
      7.1% CO2. A slight reduction in ET-1 produced by DU145 cells was also observed in
      2.2% CO2. These results illustrate that changes in ET-1 production by tumor cells
      in response to hypoxia and hypercapnia are tumor-dependent. It is clear that the
      production of ET-1 by tumor cells under normal culture conditions may not
      accurately reflect production within the tumor microenvironment. A greater
      insight into the in vivo situation, however, may be possible by modifying the
      cell culture conditions.

PMID- 9595535
TI  - Production and secretion of two vasoactive peptides, endothelin-1 and
      adrenomedullin, by a colorectal adenocarcinoma cell line, DLD-1.
AB  - Production and secretion of endothelin-1 (ET-1) and adrenomedullin (ADM) by a
      cultured human colorectal adenocarcinoma cell line, DLD-1, were studied by
      radioimmunoassay and Northern blot analysis. Both immunoreactive (IR)-ET and IR
      ADM were detected by radioimmunoassay in the culture medium of DLD-1 (IR-ET 0.86
      +/- 0.05 fmol/10(5) cells/ 24 h; IR-ADM 1.20 +/- 0.09 fmol/10(5) cells/24 h; n =
      5, mean +/- SEM). An analysis by reverse-phase high-performance liquid
      chromatography (HPLC) of the IR-ET in the culture medium showed a major
      immunoreactive peak in the position of ET-1. Reverse-phase HPLC of the IR-ADM in
      the medium showed three immunoreactive peaks, one of which eluted in the position
      of human ADM. Northern blot analysis showed the expression of ET-1 mRNA and ADM
      mRNA in the DLD-1 cells. Treatment with interferon-gamma (1-100 U/ml) for 24 h
      decreased the IR-ET levels in the culture medium but significantly increased IR
      ADM levels. This study has shown the production and secretion of two vasoactive
      peptides, ET-1 and ADM, by DLD-1 colorectal adenocarcinoma cells. The secretion
      of IR-ET was decreased by treatment with interferon-gamma. These findings suggest
      possible pathophysiologic roles for ET-1 and ADM in colon mucosal epithelial
      cells and tumors derived from them.

PMID- 9595537
TI  - Upregulation of endothelin-1 and adrenomedullin gene expression in the mouse
      endotoxin shock model.
AB  - Septic shock is a life-threatening disorder caused by lipopolysaccharide (LPS)
      and other bacterial products. Accumulating evidence indicates a role for
      vasoactive substances and cytokines in this disease process. In this study we
      examined the effect of LPS on the gene expression of endothelin-1 (ET-1) and
      adrenomedullin (AM), two major vasoactive peptides predominantly produced by
      vascular endothelial cells, to investigate their role in the pathophysiology of
      septic shock. LPS induced ET-1 and AM gene expression in the heart, lung, kidney,
      liver, and aorta within 6 h. In the liver, whereas basal ET-1 and AM mRNA were
      hardly detectable, ET-1 and AM gene expression and peptide production were
      markedly increased by LPS. This LPS-induced upregulation of ET-1 and AM
      expression is greatly potentiated by D-galactosamine (D-GalN), although D-GalN
      alone could not induce ET-1 and AM gene expression. These results, together with
      the previous findings that liver injury induced by LPS and D-GalN is mainly
      mediated by tumor necrosis factor-alpha (TNF-alpha), suggest that the LPS
      cytokine pathway may cause upregulation of ET-1 and AM production, leading to
      dysregulation of systemic and regional vascular tone.

PMID- 9595538
TI  - Endothelin-1 regulation of intercellular adhesion molecule-1 expression in normal
      and sclerodermal fibroblasts.
AB  - We investigated the potential modulation of cell surface intercellular adhesion
      molecule-1 (ICAM-1) expression and function by ET-1 in fibroblasts grown from
      skin biopsies of scleroderma (SSc) patients compared with healthy controls.
      Surface ICAM-1 expression was quantified by cell-bound ELISA and by FACS
      analysis. ICAM-1 function was investigated by measuring cell adhesion, and we
      studied ICAM-1 gene expression using RT-PCR. Fibroblast ET-1 binding sites were
      measured using 125I-labeled ET-1, and the modulation of ICAM-1 function by ET-1
      was determined by measuring the binding of human U937 cells to fibroblasts in the
      presence of a mixed ETA/B receptor antagonist (bosentan) or a neutralizing anti
      ICAM-1 antibody. ICAM-1 expression was significantly higher in SSc fibroblasts
      compared with normal controls. ET-1 increased ICAM-1 on both normal and SSc
      fibroblasts to comparable levels. RT-PCR demonstrated that ICAM-1 mRNA was
      upregulated by ET-1, and results from binding studies showed fibroblasts exposed
      to ET-1 supported more U937 cells than controls, a process that could be
      inhibited by bosentan and ICAM-1 neutralizing antibody. Autoradiography showed ET
      1 receptors on both normal and SSc fibroblasts. Our findings indicate that SSc
      fibroblasts express intrinsically elevated levels of surface ICAM-1 and message.
      ET-1 can induce normal fibroblasts to express some SSc phenotypes and may
      function as a potent proinflammatory mediator, similar to cytokines, and
      therefore may also have immunoregulatory functions for immune cells infiltrating
      and binding to connective tissues.

PMID- 9595540
TI  - Characterization of endothelin receptors in isolated, perfused human spleen.
AB  - At present, there is no information on endothelin-1 (ET-1)-mediated vascular
      effects in the human spleen. The objectives of this study were to investigate the
      in vitro vascular responses to ET-1 using pharmacologic probes (selective ET
      receptor agonists/antagonists) and to characterize the ET receptor population in
      the human spleen. Spleens (n = 6) were removed from patients for treatment of
      underlying disease. The organs were perfused with warmed (37 degrees C),
      oxygenated (95% O2/5% CO2) Krebs solution at constant flow, with continuous
      recording of splenic arterial perfusion pressure (SAPP). The increases in SAPP
      caused by injection of ET-1 (ETA/ETB agonist) were markedly reduced in the
      presence of the selective ETA antagonist FR-139317, whereas those induced by IRL
      1620 (an ETB agonist) and norepinephrine (NE) were unchanged. The increases in
      SAPP induced by intra-arterial bolus injections of NE and ET-1 were significantly
      (p < 0.05) potentiated by indomethacin [INDO; a cyclo-oxygenase (COX) inhibitor]
      alone and the responses to both peptides (ET-1 and IRL-1620) were significantly
      (p < 0.05) potentiated by INDO and L-NAME [a nitric oxide (NO) synthase
      inhibitor] together. We conclude that ET-1 contributes to the regulation of
      vascular tone in human spleen through activation of both ETA and ETB receptors
      and that these responses are modulated by concomitant release of prostaglandins
      and NO.

PMID- 9595539
TI  - In vivo role of endothelin-converting enzyme-1 as examined by adenovirus-mediated
      overexpression in rats.
AB  - We previously reported that adenovirus-mediated overexpression of endothelin-1
      (ET-1) elevates systemic blood pressure in rats. In this model, plasma big ET-1:
      ET-1 ratios were almost 30, whereas they were only 5 in the control group,
      suggesting that endothelin-converting enzyme (ECE) may be a rate-limiting step in
      the production of ET-1 under these conditions. To further investigate the role of
      ECE in vivo, we prepared recombinant adenovirus strains carrying a soluble,
      secretory form of bovine ECE-1 cDNA (Ad.CMV. secECE), human ET-1 cDNA (Ad.CMV.ET
      1), and, as a control, E. coli lacZ (Ad.CMV.beta-gal). Ad.CMV.secECE (1-10 x
      10(9) pfu/ml) was injected into the caudal vein of male Wistar rats and the
      animals were studied 96 h later. Immunoblot analysis of circulating plasma
      confirmed the expression of the soluble ECE-1. The plasma levels of big ET-1 and
      mature ET-1 were similar in Ad.CMV.secECE and Ad.CMV.beta-gal groups (0.3-0.5
      pM). When Ad.CMV.secECE was co-injected with Ad.CMV.ET-1 (2.5 x 10(9) pfu/ml
      each), plasma ET-1 levels were significantly elevated compared to the control
      group co-injected with Ad.CMV.secECE and Ad.CMV.beta-gal (10.2 +/- 2.4 vs. 1.1 +/
      0.2 pM). Big ET-1 levels were threefold higher (3.7 +/- 1.1 vs. 1.2 +/- 0.4 pM),
      and systemic blood pressure was significantly elevated (132 +/- 3 vs. 90 +/- 3 mm
      Hg) in the Ad.CMV.secECE + Ad.CMV.ET-1 group. Administration of an ECE inhibitor
      (CGS 26303, 30 mg/kg) significantly reduced the blood pressure in the
      Ad.CMV.secECE + Ad.CMV.ET-1 group (from 125 +/- 5 to 74 +/- 6 mm Hg) but not in
      the control group (from 85 +/- 2 to 75 +/- 3 mm Hg). Infusion of an ETA
      antagonist (FR 139317; 0.2 mg/kg/min for 30 min) also significantly reduced the
      blood pressure only in the Ad.CMV.secECE + Ad.CMV.ET-1 group, without any
      significant effect in the control group. This study demonstrates that even though
      overexpression of ECE-1 in itself does not lead to systemic hypertension, the
      enzyme can be a crucial rate-limiting factor in the production of mature ET-1 in
      vivo. Furthermore, this model may prove to be useful for in vivo screening of ECE
      inhibitors.

PMID- 9595541
TI  - Apoptosis in kidneys of endothelin-1 transgenic mice.
AB  - Endothelin-1 (ET-1) transgenic mice are characterized by age-dependent
      development of renal cysts and renal fibrosis (interstitial fibrosis and
      glomerulosclerosis), leading to a progressive decrease in glomerular filtration
      rate. The mechanism causing the loss of functionally and morphologically normal
      renal tissue is unknown. An imbalance between cell proliferation and apoptosis in
      the kidneys of ET-1 transgenic mice might contribute to this process. We
      identified apoptotic cells in kidney sections by in situ end-labeling and by the
      typical nuclear chromatin morphology after propidium iodide (PI) staining. Cell
      proliferation was measured by estimating the proliferating cell nuclear antigen
      (PCNA)-positive cells. The numbers of apoptotic cells were significantly
      increased (p < 0.001) in the kidneys of 14-month-old ET-1 transgenic mice,
      whereas cell proliferation was not enhanced. Apoptotic cells were detected in the
      glomeruli, tubular cells, and renal interstitial cells in ET-1 transgenic mice.
      In conclusion, apoptotic loss of functional renal tissue appears to be associated
      with the progression of cyst formation and renal fibrosis. Therefore, an
      imbalance between cell proliferation and apoptosis could be an important cellular
      mechanism in ET-1 transgenic mice leading to end-stage kidney disease.

PMID- 9595542
TI  - Systemic and renal response to salt loading in endothelin-1 knockout mice.
AB  - Endothelin-1 (ET-1) knockout mice demonstrate elevated blood pressure, which may
      be associated with disturbance in central cardiorespiratory regulation. In this
      study we examined responses to salt loading in ET-1 knockout mice to investigate
      whether ET-1 is involved in the pathophysiology of salt-sensitive hypertension.
      Male Edn1+/- heterozygous mice and their wild-type littermates were fed either a
      high NaCl (8%) or a normal (0.2%) diet for 4 weeks. Systemic blood pressure and
      tissue ET-1 levels were measured as well as several parameters relating to sodium
      handling and volume homeostasis. On normal diet, renal ET-1 levels of Edn1+/-
      mice were about 50% of those of wild-type mice. A high-salt diet caused a
      significant decrease in renal ET-1 levels by about 50% in both groups. Urine
      volume, urinary sodium excretion, and FENa in mice on the 8% NaCl diet were
      significantly higher than those in mice on the 0.2% NaCl diet, whereas there were
      no differences in circulating plasma volume, serum electrocytes, and creatinine
      clearance. These responses were similar in Edn1+/- and wild-type mice. Although
      systemic blood pressure was significantly higher in Edn1+/- mice than in the wild
      type, the effect of salt loading on blood pressure was not significant in either
      Edn1+/- or wild-type mice. We conclude that changes in ET-1 production within a
      physiologic range do not affect salt sensitivity, although renal ET-1 content is
      decreased by salt loading.

PMID- 9595543
TI  - Pharmacology of endothelins in vascular circuits of normal or heterozygous
      endothelin-A or endothelin-B knockout transgenic mice.
AB  - Endothelin-1 (ET-1; 0.001-1 nmol) and the ETB receptor agonist IRL-1620 (0.01-1
      nmol) induced a dose-dependent vasoconstriction of the arterial and venous
      mesenteric circuits and of the kidney in normal mice. BQ-123 (10(-7) M) or BQ-788
      (10(-7) M) abolished the vasoconstriction induced by ET-1 in the arterial
      mesenteric and renal vasculatures without affecting that of norepinephrine (NE).
      In the venous mesenteric vasculature, only BQ-123 reduced the response to ET-1
      but not to NE. In other experiments we compared the mesenteric and renal vascular
      reactivities to ET-1 and IRL-1620 in ETA or ETB heterozygous knockout mice with
      those of the wild-type strain. We observed a significant reduction in vascular
      reactivity to ET-1 but not to IRL-1620 in the arterial mesenteric and renal but
      not the venous mesenteric circuits of ETA knockout mice. In contrast, there was a
      significant reduction in vascular reactivity to ET-1 and IRL-1620 in the arterial
      mesenteric and renal circuits of ETB knockout mice. In the venous mesenteric
      vasculature, only the vasoconstriction induced by IRL-1620 was significantly
      reduced in the same ETB knockout strain. Our results suggest that, in the mouse,
      arterial mesenteric and renal vasoconstriction to ET-1 is mediated by both
      subtypes of ET receptors, whereas venous mesenteric vasoconstriction appears to
      be mediated uniquely by the ETA receptor subtype. Knockout of only one allele of
      the ETA or ETB gene appears to be sufficient for reduction of the ET-1 or IRL
      1620 vasoconstrictor effects in the mesenteric and renal vascular beds of the
      mouse.

PMID- 9595545
TI  - Plasma (total and ionized), erythrocyte and platelet magnesium levels in renal
      transplant recipients during cyclosporine and/or azathioprine treatment.
AB  - We evaluated total and ionized plasma magnesium levels, and erythrocyte and
      platelet magnesium concentrations from two groups of renal transplant recipients
      treated either with cyclosporine, azathioprine and prednisolone (group CAP, n =
      8) or with azathioprine and prednisolone (group AP, n = 13), and in a group of
      age- and sex-matched healthy subjects (n = 10). Reduced plasma (total and
      ionized), erythrocyte and platelet magnesium concentrations were found in both
      CAP and AP groups with respect to controls (CAP: total plasma Mg median 0.61 vs
      0.86 mmol/L, p < 0.01, ionized plasma Mg median 0.43 vs 0.58 mmol/L, p < 0.001,
      erythrocyte Mg median 2.18 vs 2.56 mmol/L, p < 0.05, platelet Mg median 1.75 vs
      2.84 mmol/10(8) cells, p < 0.001; AP: total plasma Mg median 0.62 vs 0.86 mmol/L,
      p < 0.01, ionized plasma Mg median 0.48 vs 0.58 mmol/L, p < 0.001, erythrocyte Mg
      median 2.30 vs 2.56 mmol/L, p < 0.05, platelet Mg median 1.75 vs 2.84 mumol/10(8)
      cells, p < 0.001), while no difference was found between the two groups of
      transplant recipients as regards plasma and intracellular magnesium levels.
      Magnesium fractional excretion was higher in transplant recipients than in the
      control group (Mg fractional excretion median AP 18.6 per cent and CAP 12.8 per
      cent vs controls 3.5 per cent), whereas no difference was found between patients
      and control subjects for urinary magnesium 24h excretion. Moreover, in the whole
      group of transplant recipients (n = 21), urinary magnesium showed an inverse
      correlation with platelet (rs = -0.54, p < 0.05) and ionized plasma magnesium (rs
      = -0.48, p < 0.05), and time after transplantation showed a negative correlation
      with platelet magnesium concentrations (rs = -0.73, p < 0.001), and a direct
      correlation with fractional magnesium excretion (rs = 0.53, p < 0.05). Finally, a
      direct relationship between platelet magnesium and ionized plasma magnesium was
      also detected in the whole group of transplant recipients (rs = 0.47, p < 0.05).
      Both intraplatelet magnesium depletion and ionized plasma magnesium reduction
      induced by immunosuppressive therapy could be involved in the increased risk from
      atherosclerotic disease in renal transplant recipients.

PMID- 9595544
TI  - Association of low plasma concentrations of antioxidant vitamins, magnesium and
      zinc with high body fat per cent measured by bioelectrical impedance analysis in
      Indian men.
AB  - This cross-sectional study was conducted to determine the association of high
      body fat per cent measured by bioelectric impedance analysis with known risk
      factors of obesity as well as with serum levels of vitamins, trace elements and
      magnesium and oxidative stress in an urban population in India. There were 850
      men aged 25-64 years, randomly selected from the city of Moradabad. Subjects were
      divided into high body fat per cent (n = 357), over fat per cent (n = 230),
      desirable fat (n = 200) and low fat (n = 63) based on criteria of body fat per
      cent analysis. The prevalence of central obesity, sedentary lifestyle, family
      history and higher visible fat intake showed significant association with higher
      over fat per cent. Postprandial plasma insulin and glucose and serum iron and
      oxidative stress were significantly higher and plasma levels of vitamin C and E
      and serum zinc/insulin ratio as well as serum magnesium/insulin ratio showed
      inverse association with high body fat per cent. Multivariate logistic regression
      analysis after adjustment of age showed a significant positive association of
      body mass index (odds ratio 0.97), sedentary lifestyle (odds ratio 1.12) and
      serum iron (OR 1.00) with higher body fat per cent. Zinc (OR 1.03), magnesium (OR
      1.02), vitamins C (OR 1.08 and E (OR 1.09) deficiency were risk factors of higher
      body per cent and central obesity. It is possible that some Indian men can
      benefit by increased intake of zinc, magnesium, vitamin C and vitamin E in
      conjunction with lifestyle changes.

PMID- 9595546
TI  - Clinical study on magnesium and calcium level in the blood during the acute
      pancreatitis.
AB  - The aim of this clinical study was to determine whether during the course of mild
      gallstone pancreatitis (I degree), which is the most common form of acute
      pancreatitis, there occur blood magnesium and calcium concentration disruptions.
      Testing was performed on 20 patients suffering from mild pancreatitis during 5
      days of illness. Results were compared with a group of 110 healthy individuals
      (first-time blood donors). The average plasma magnesium ion concentration (PMg++)
      was lowest in the first day of illness and gradually goes up during the following
      4 days. The highest levels, exceeding 11 per cent basal values, were observed
      during the fifth day of acute pancreatitis. Similar changes of blood cells
      magnesium ion concentration (BCMg++) were observed. The lowest level was found
      during the first day and after this it increased slightly to reach average
      levels. The most stable was plasma calcium ion concentration (PCa++) which did
      not indicate any variations. Blood donors results: PMg++ mean 0.95 +/- 0.17
      mmol/L (range 0.65-1.41 mmol/L), BCMg++ -2.85 +/- 0.42 mmol/L (1.58-3.62 mmol/L),
      PCa++ -2.51 +/- 0.28 mmol/L (2.03-2.99 mmol/L). The observed differences in
      magnesium concentration were statistically significant only for the group
      examined (p < 0.001) and did not differ in a statistically significant sense from
      the control group values (Cohran-Cox test with p < 0.001). Previous studies have
      shown that, among individuals with mild gallstone pancreatitis, there is half the
      bile magnesium ion concentration and the same bile calcium ion concentration as
      among individuals with gallstones, who have not suffered from pancreatitis. Lack
      of permanent blood ion changes during the course of this form of the disease
      shows that the general circulating pool is unchanged. This magnesium deficiency
      pertains specifically to bile. However during the course of acute pancreatitis
      and lack of oral magnesium supply the pool of body reserves may be depleted.
      Magnesium also shows pharmacodynamic action as a tranquilliser, a vasodilator, a
      cytoprotective agent, an anticoagulant, an antioxidant and a myorelaxant. All
      these influences are beneficial in acute pancreatitis treatment. Therefore,
      despite visible features of magnesium deficit in the organism, it seems
      reasonable to supply the daily need by adding 2 amp. 25 per cent magnesium
      sulphate (total 40.5 mmol) during parenteral fluids infusion. Such a procedure
      was carried out for our patients and the results will be presented in a separate
      publication.

PMID- 9595547
TI  - Magnesium status and ageing: an update.
AB  - Ageing constitutes a risk factor for magnesium deficit. Primary magnesium deficit
      originates from two etiological mechanisms: deficiency and depletion. Primary
      magnesium deficiency is due to insufficient magnesium intake. Dietary amounts of
      magnesium are marginal in the whole population whatever the age. Nutritional
      deficiencies are more pronounced in institutionalized than in free-living ageing
      groups. Primary magnesium depletion is due to dysregulation of factors
      controlling magnesium status: intestinal magnesium hypoabsorption, reduced
      magnesium bone uptake and mobilisation, sometimes urinary leakage,
      hyperadrenoglucocorticism by decreased adaptability to stress, insulin-resistance
      and adrenergic hyporeceptivity. Secondary magnesium deficit in ageing largely
      results from various pathologies and treatments common to elderly persons: i.e.
      non insulin dependent diabetes mellitus and use of hypermagnesuric diuretics.
      Magnesium deficit may participate in the clinical pattern of ageing: mainly
      neuromuscular, cardiovascular and renal symptomatologies. The consequences of
      hyperadrenoglucocorticism--whose non response to dexamethasone suppression test
      appears the simplest marker--may concern immunosuppression, muscle atrophy,
      centralization of fat mass, osteoporosis, hyperglycemia, hyperlipidemia,
      atherosclerosis, disturbances in mood and mental performances through accelerated
      hippocampal ageing particularly. Treatment of magnesium deficiency requires
      simple oral physiological magnesium supplementation. Treatment of the different
      types of magnesium depletion leads to a more or less specific control of
      pathophysiological disturbances of the required magnesium substrate. Open and
      double blind studies on the effects of the treatments of magnesium deficiency and
      of magnesium depletions in geriatic populations are too scarce. Further study is
      necessary to assess the accurate place of magnesium deficit in the
      physiopathology of ageing.

PMID- 9595548
TI  - New experimental and clinical data on the efficacy of pharmacological magnesium
      infusions in cerebral infarcts.
AB  - Multiple metabolic processes have been identified within the critically perfused
      ischaemic penumbra on the margins of cerebral infarcts. Intervention in many of
      these processes has been neuroprotective, notably blockade of glutamate receptors
      such as the N-methyl D-aspartate (NMDA) receptor. Magnesium may act as a
      neuroprotective agent through vascular effects (increasing regional cerebral
      blood flow to ischaemic tissue, anticonstrictor effects against vascular
      mediators, vasodilatation of the cerebral circulation) or neuronal effects.
      Neuronal effects include block of the NMDA receptor ion channel, calcium
      antagonism at voltage-gated channels, enhanced buffering of intracellular calcium
      ions, and enhanced regeneration of adenosine triphosphate. Magnesium infusions of
      sulphate or chloride salts are significantly neuroprotective in standard animal
      focal cerebral ischaemia models, with benefits being evident at serum
      concentrations attainable in humans. Mg systemic infusion causes rises in
      cerebrospinal fluid and brain magnesium concentrations. Magnesium is also
      neuroprotective in other models of cerebral ischaemia. Three clinical trials in
      acute stroke have involved just over 100 patients. No adverse effects have been
      observed, and trends favouring magnesium treatment have been seen. A large
      multicentre clinical trial testing the efficacy of magnesium sulphate is
      underway, and should report within 4 years.

PMID- 9595549
TI  - Cationic lipids, phosphatidylethanolamine and the intracellular delivery of
      polymeric, nucleic acid-based drugs (review).
AB  - Polymeric, nucleic acid drugs must be protected from endogenous nucleases and
      delivered to target cell nuclei in order to maximize their activity. Constructs
      expressing therapeutic genes, antisense oligonucleotides and ribozymes can be
      delivered into cells by viral vectors, but concerns over safety and clinical
      utility have led to research into the development of alternative, non-viral
      delivery systems. Antisense and ribozyme drug development has focused upon
      modifications to the natural oligonucleotide chemistry which make the molecules
      resistant to nuclease degradation. These novel oligonucleotides cannot be
      generated by transgenes and must be administered in similar fashion to
      conventional drugs. However, oligonucleotides cannot cross membranes by passive
      diffusion and intracellular delivery for these drugs is very inefficient. Here we
      review the recent advances in forming lipid-DNA particles designed to mimic viral
      delivery of DNA. Most evidence now supports the hypothesis that lipid-DNA drugs
      enter target cells by endocytosis and disrupt the endosomal membrane, releasing
      nucleic acid into the cytoplasm. The mechanisms of particle formation and
      endosome disruption are not well understood. Cationic lipids are employed to
      provide an electrostatic interaction between the lipid carrier and polyanionic
      nucleic acids, and they are critical for efficient packaging of the drugs into a
      form suitable for systemic administration. However, their role in endosome
      disruption and other aspects of successful delivery leading to gene expression or
      inhibition of mRNA translation are less clear. We discuss the propensity of lipid
      nucleic acid particles to undergo lipid mixing and fusion with adjacent
      membranes, and how phosphatidylethanolamine and other lipids may act as factors
      capable of disrupting bilayer structure and the endosomal pathway. Finally, we
      consider the challenges that remain in bringing nucleic acid based drugs into the
      realm of clinical reality.

PMID- 9595550
TI  - In vitro folding of a membrane protein: effect of denaturation and renaturation
      on substrate binding by the lactose permease of Escherichia coli.
AB  - Site-directed mutagenesis and site-directed fluorescence spectroscopy demonstrate
      that Cys148 interacts hydrophobically with the galactosyl moiety of substrates of
      the lactose permease of Escherichia coli. By taking advantage of the finding that
      labelling of single-Cys148 permease with the thiol-specific fluorophore 2-(4'
      maleimidylanilino)naphthalene-6-sulfonic acid (MIANS) is blocked specifically by
      substrates of the permease, it is demonstrated that the high-affinity ligand
      beta,D-galactopyranosyl 1-thio-beta,D-galactopyranoside (TDG) stabilizes
      solubilized, purified permease against heat denaturation. Furthermore, TDG
      protection against MIANS labelling of single-Cys148 permease is abolished by
      guanidinium hydrochloride. After dialysis of the denaturant, TDG protection
      against MIANS labelling is recovered, indicating that the permease has been
      refolded. The conclusion is confirmed and extended by studying site-directed
      fluorescence of purified single-Cys331 permease, where the emission spectrum of
      the MIANS-labelled protein is differentially altered by low or high
      concentrations of TDG. The results demonstrate that both low- and high-affinity
      binding, as well as ligand-induced conformational changes in the permease, can be
      denatured reversibly in vitro.

PMID- 9595551
TI  - Cell surface localization of the 78 kD glucose regulated protein (GRP 78) induced
      by thapsigargin.
AB  - In the present study it was found that the synthesis of the 78 kD glucose
      regulated protein (GRP 78 or BIP) is vigorously induced in human rabdomiosarcoma
      cells (TE 671/RD) following both short-term (1 h) and prolonged (18 h) exposure
      to 100 nM thapsigargin (Tg). Flow cytometric analysis with a specific anti-GRP 78
      polyclonal antibody showed that Tg-treated cells express the GRP 78 on the plasma
      membrane. Cell surface localization of the Tg-induced GRP 78 was confirmed by
      biotinylation of membrane-exposed proteins and subsequent isolation of the biotin
      labelled proteins by streptavidin/agarose affinity chromatography. It was found
      that a fraction of the Tg-induced GRP 78 is present among the biotin-labelled,
      surface-exposed, proteins. Conversely, the GRP 78 immunoprecipitated from
      unfractionated lysates of Tg-treated and biotin-reacted cells was found to be
      biotinylated. This is the first report demonstrating surface expression of GRP 78
      in cells exposed to a specific GRP 78-inducing stimulus.

PMID- 9595552
TI  - Phosphoinositide metabolism and shape control in sheep red blood cells.
AB  - Metabolic depletion of sheep red blood cells leads to decreased intracellular
      concentrations of ATP and reduced glutathione as well as degradation of
      phosphoinositides. In sheep red blood cells, depletion of ATP induced two types
      of shape transformation: one early phase involving formation of protrusions on
      the cell surface similar to those observed upon depletion of human red blood
      cells; and one late phase, in which the sheep red blood cells develop long, rod
      shaped projections. During the initial stages of shape changes, degradation of
      the phosphoinositides parallels the discocyte-echinocyte transformation, thus
      giving further support to a shape-controlling mechanism based on the bilayer
      couple hypothesis. However, formation of the long projections does not coincide
      with turnover of the phosphoinositides but rather with the level of reduced
      glutathione. This indicates that development of these rod-like extensions on the
      cell surface is induced by oxidative processes that may well involve cross
      linking of membrane skeleton proteins.

PMID- 9595554
TI  - [Future of the therapy of dementia--current data on Ginkgo-Special Extract EGB
      761].

PMID- 9595553
TI  - Estimation of structural similarity of membrane proteins by hydropathy profile
      alignment.
AB  - Many membrane proteins consist of bundles of alpha-helices that are reflected in
      typical hydropathy profiles of the amino acid sequences. The profiles provide a
      link between the amino acid sequence of the polypeptide chain and its folding and
      are much better conserved during evolution than the amino acid sequences from
      which they are deduced. In this paper, the hydropathy profiles are used to
      compare structures of membrane proteins or families of membrane proteins. A
      technique is proposed that computes the optimal alignment of hydropathy profiles
      without making use of the underlying sequences. The results show that two
      membrane proteins with only marginal sequence identity or two non-related
      families of membrane proteins can have very similar hydropathy profiles,
      indicating similar global structures. Two parameters are defined that measure
      differences between hydropathy profiles. The Structure Divergence Score (SDS)
      provides a measure for the divergence in profiles that reflect one and the same
      global structure. The SDS is derived from the individual hydropathy profiles of
      the members of a homologous protein family that are believed to share the same
      structure. The Profile Difference Score (PDS) quantifies the difference between
      two hydropathy profiles. Comparison of the PDS of the optimal alignment of the
      hydropathy profiles of two families of membrane proteins with the SDSs of the two
      families provides a criterion for structural similarity. Using this technique,
      pairwise alignment of the family profiles of eight families of secondary
      transporters suggests that the families fall into four structural classes.

PMID- 9595555
TI  - Development of postural control, a basic aspect of neuro-ontogeny.

PMID- 9595556
TI  - Postural control systems in developmental perspective.
AB  - How can the adult postural organisation be elucidated using an ontogenetic
      approach, and what questions can be raised about ontogenesis starting from the
      organisation of adult posture? These questions will be addressed taking three
      aspects of postural organisation. The first is the internal representation of
      erect posture, including the role played by the various sensory inputs in this
      representation. The second aspect relates to the variables which are controlled
      during erect posture: is it the body orientation with respect to the vertical or
      the localisation of the centre of gravity with respect to the feet which is
      controlled? The third aspect concerns the coordination between posture,
      equilibrium and movement, focusing on the role played by an internal
      representation of the external world and its interactions with the body segments
      in organising the anticipatory postural adjustments. The central organisation of
      coordinated control will also be considered. Each of these aspects will be
      discussed in relation to ontogenetic considerations.

PMID- 9595557
TI  - Origin and processing of postural information.
AB  - This contribution surveys the sources and the processing of spatial information
      about posture, that is, about the orientation of the body and its parts with
      respect to the vertical (whereas 'position' designates their orientation to each
      other). Postural information is, to a considerable extent, gained by sense organs
      in the head. Hence information gained by the mobile eyes and the pitched-up
      labyrinths is first transformed from a retinal and otolithic into a head-fixed
      frame of reference, then from head- to trunk-fixed coordinates, and, finally,
      from a trunk-fixed to an exocentric frame of reference. To that end the position
      of eyes and otoliths to the head, of the head to the trunk, and of the trunk to
      the rest of the world must be known, deduced by efference copies or measured by
      proprioceptors. It is shown that the perceived relation of the visual world to
      the vertical is exclusively determined by sense organs in the head, whereas body
      posture is also directly measured by recently discovered graviceptors in the
      human trunk. It appears that the proprioceptors mediate perception of position,
      but not, or only indirectly, of posture.

PMID- 9595558
TI  - The final common pathway in postural control--developmental perspective.
AB  - A brief review is given concerning postural specialisations among mammalian
      muscle fibres and motor units. Most skeletal muscles contain a mixture of fibres
      with different characteristics, and their slow-twitch (S) units are well-known to
      possess properties suitable for postural tasks: they are highly fatigue
      resistant, well equipped for oxidative metabolism, and their slowness makes them
      energetically cheap in (semi-)isometric contractions. These features are
      adequately employed in motor behaviour owing to characteristics of the associated
      motoneurones. In adult mammals, the way in which a muscle is used can influence
      its proportion of S units. This adjustment occurs within a restricted 'adaptive
      range' which differs between muscles and animal species, presumably being preset
      at an early age. In the course of early foetal development, part of the slow vs.
      fast differentiation of muscle fibre properties can take place independently of
      innervation. Once innervation has taken place, however, motoneurones influence
      the differentiation in various ways. On the whole, a well coordinated timing
      seems to exist between the early differentiation of central motor mechanisms and
      of the peripheral machinery, largely causing the neuromuscular system to
      be/become ready for use when the brain needs it.

PMID- 9595560
TI  - Evidence for a load receptor contribution to the control of posture and
      locomotion.
AB  - A basic aspect of the neuronal control of bipedal stance and gait represents the
      antigravity function of leg extensors. Proprioceptive reflexes involved in the
      maintenance of body equilibrium depend on the presence of contact forces opposing
      gravity. Extensor load receptors are thought to signal changes of the projection
      of the body's centre of mass with respect to the feet. According to recent
      observations in the spinal cat, this afferent input probably arises from Golgi
      tendon organs and represents a newly discovered function of these receptors in
      the regulation of stance and gait. In humans, evidence for a significant
      contribution of the load receptor to leg muscle activation has come from
      immersion experiments. Compensatory leg muscle activation depends on the actual
      body weight. Furthermore, recent experiments in paraplegic patients showed that
      the beneficial effects of a locomotor training critically depends on the initial
      degree of body unloading and reloading during the course of the training period.

PMID- 9595559
TI  - The anatomy of the central control of posture: consistency and plasticity.
AB  - Posture is usually thought to be steered by brainstem and cortical structures
      that have access to the motoneurons and their premotor interneurons of the axial
      and neck muscles. The present paper describes these pathways and their relation
      with gaze control structures. All these systems belong to the medial component of
      the so-called voluntary motor system. On the other hand, in the cat there also
      exist several postures that are not steered by the somatic, but by the emotional
      motor system. Examples are arching of the back and mating postures. The pathways
      thought to be involved in these behaviours are described. They belong to the
      lateral component of the emotional motor system and, especially in case of mating
      postures, are extremely plastic. They have been demonstrated to be almost 10
      times as strong in oestrus than in non-oestrus cats.

PMID- 9595561
TI  - Development of postural control--differences between ventral and dorsal muscles?
AB  - Postural control is organized in basic, direction specific synergies which can be
      adapted to task-related conditions. Studies on the development of postural
      adjustments in young sitting children revealed that largely variable, direction
      specific muscle activation patterns are already present in 5-6 month old children
      not able to sit without support. With increasing age, the variation in muscle
      activation patterns decreases, resulting in a selection of the most complete
      patterns of synergist activation at 9-10 months of age. The synergy of the dorsal
      extensor muscles (during a forward sway of the body) develops faster than the
      synergy of the ventral flexors (during backward body-sway). A 'fixed' extensor
      synergy is prominently present between 9 months and 3 years, i.e. during the
      period when standing and walking abilities develop. With increasing age the
      'fixed' extensor synergy gradually dissolves. The flexor synergy shows a larger
      flexibility than the extensor synergy, a difference which can be attributed to
      differences in stability limits and differences in the degree of supraspinal
      modulation.

PMID- 9595562
TI  - Postural control during reaching in young infants: a dynamic systems approach.
AB  - We conceptualize the coordinated development of posture and reaching within
      Schoner's (Ecological Psychology, 7:291-314, 1995) dynamic model of coupled
      levels of control: load, timing, and goal. In particular, the goal of postural
      stability must be maintained during a reach. Using longitudinal data from four
      infants followed from 3 weeks to 1 year, we show that coordination of the head
      with upper and lower arm activity is critical for successful reaching. First,
      infants acquire stable head control several weeks before reaching onset.
      Furthermore, reaching onset is characterized by a reorganization of muscle
      patterns to include more trapezius and deltoid activity, serving to stabilize the
      head and shoulder and provide a stable base from which to reach. We argue that
      initially, the system is working on postural stability and reaching as goals.
      Infants secondarily select appropriate muscle patterns to achieve those goals
      depending, in part, on their individual body sizes, body proportions and energy
      levels. Motor development proceeds as a continual dialogue between the nervous
      system, body, and environment.

PMID- 9595563
TI  - Eye, head and trunk control: the foundation for manual development.
AB  - Mastery of reaching and manipulation relies on adequate postural control. The
      trunk must be balanced relative to a base of support to allow free movements of
      the arms and hands. Moreover, the head must be supported flexibly by the trunk so
      that gaze can be directed toward the target to provide a spatial frame of
      reference for reaching. For fine manipulation it is also crucial to avoid retinal
      slips which would introduce blur. Stabilizing gaze is generally accomplished
      through adjustments of both eye and head position. Until gaze is stabilized, it
      is difficult to establish a frame of reference between the target and the self.
      Thus, a nested hierarchy of support involving the eyes, head, and trunk forms an
      important foundation for manual activity.

PMID- 9595564
TI  - The development of postural response patterns during reaching in healthy infants.
AB  - Reaching movements in adults are accompanied by complex postural adjustments
      which are controlled by spatial, temporal, and quantitative parameters. The basic
      postural adjustments are selected on the basis of the spatial parameter, whereas
      fine tuning of the pattern is guided by temporal and quantitative parameters. In
      specific conditions, such as during fast arm movements, postural adjustments have
      an anticipatory character. Recently, the development of postural adjustments
      during reaching was studied longitudinally in infants aged 3-18 months, placed in
      supine and sitting positions. The data revealed that already at 4 months, the age
      at which successful reaching emerges, reaching movements are accompanied by
      complex postural adjustments. The early postural patterns resembled the adult
      ones in spatial features (dorso-ventral ordering), temporal characteristics (top
      down recruitment), and position dependency. With increasing age the postural
      patterns changed considerably, including a transient period of less extensive
      postural activity at 6-8 months, the age at which rolling, sitting up and
      crawling develops. Postural anticipation during reaching was not consistently
      present at any age.

PMID- 9595565
TI  - Development of locomotor balance control in healthy children.
AB  - A set of experimental studies showing how inter-segmental coordination develops
      during childhood in various locomotor tasks is reviewed. On the basis of these
      results and two functional principles (stable reference frame and control of the
      degrees of freedom of the body joints), we recently proposed an ontogenetic model
      for the sensorimotor organization of balance control in humans (5). In this
      model, the hypothesis was put forward that the two main modes of equilibrium
      control (ascending vs descending temporal organization) operate alternatively and
      are associated with either of two modes of head-trunk linkage ('en bloc' vs
      articulated) during four successive periods in the course of ontogenesis. The
      advantage of this model is that it is heuristic and therefore open to further
      improvements, including the generalization of these balance strategies to most of
      the posturo-kinetic activities, the comparison between unperturbed natural
      balance and reactions to postural disturbances. Some improvements are suggested,
      and are illustrated by the studies of intersegmental coordination in new
      experimental tasks such as hops using one foot or two feet and the initiation of
      gait. These new results are consistent with the idea that mastery of the degrees
      of freedom to be controlled simultaneously during the movement improves gradually
      with age. Moreover, they support the concept of multiple reference frames which
      operate in a complementary manner or in concert to permit the most appropriate
      organization of balance control, depending on the environmental requirements.

PMID- 9595566
TI  - Development of anticipatory orienting strategies during locomotor tasks in
      children.
AB  - Some basic problems related to the development of goal-directed locomotion in
      humans are reviewed here. A preliminary study is presented which was aimed at
      investigating the emergence of anticipatory head orienting strategies during goal
      directed locomotion in children. Eight children ranging from 3.5 to 8 years had
      to walk along a 90 degrees right corner trajectory to reach a goal, both in light
      and in darkness. The instantaneous orientation in space of the head, trunk, hips
      and left foot antero/posterior axes was computed by means of an ELITE four-TV
      camera, 100 Hz system. The results showed that predictive head orienting
      movements can occur also in the youngest children. The head starts to rotate
      toward the goal before the corner point of the trajectory is reached. In
      children, the head peak rotation coincides with the trajectory corner while in
      adults the peak is attained before. In children, the walking speed is largely
      decreased in darkness. The results suggest that feedforward control of goal
      directed locomotion appears very early in gait development and becomes
      increasingly important afterwards.

PMID- 9595567
TI  - Development of posture and locomotion in free-ranging primates.
AB  - Postural and locomotor development is described for free-ranging groups of three
      monkey species: Macaca mulatta (rhesus macaque), M. radiata (bonnet macaque) and
      Presbytis entellus (hanuman langur). Behaviors are discussed in terms of infant
      1, infant-2, juvenile, adult and elderly age groups. Analysis is based on high
      speed motion pictures and videos. Infant-1 monkeys continually cling to their
      mother's ventral surface with strong hand and foot grasps. Independent motor
      coordination develops during the infant-2 period. The greatest postural and
      locomotor activity, both qualitatively and quantitatively, is achieved during the
      juvenile period. The adult and elderly periods are characterized by a progressive
      reduction in the variety and, eventually, quality of these motor abilities.
      Macaques and langurs differ, however, in the course of their behavioral
      development. These findings have implications for concepts of underlying neural
      mechanisms, indicate possible species differences in the development of these
      mechanisms, and demonstrate that the spectrum of volitional behaviors practiced
      by different age groups of free-ranging animals is broader than that observed in
      the laboratory setting.

PMID- 9595568
TI  - Posture and locomotion in the rat: independent or interdependent development?
AB  - In this essay, recent research into the relation between postural control and the
      development of walking in the rat is reviewed. The adult-like walking pattern
      develops at the 15th to 16th day (P15-P16). Until this age, postural control, as
      indicated by EMG activity in the longissimus muscle in the trunk, is poorly
      phased in relation to the stepcycle. After P15-P16, accuracy increases but only
      after P21 is the adult pattern of EMG activity in the trunk muscles in relation
      to locomotor activity in the hindpaw muscles established. Neuroanatomical
      research revealed that those muscles in trunk and extremities which fulfil
      important postural tasks are innervated by motoneuronal pools containing
      conspicuous dendrite bundles. These bundles emerge at about the age when the
      adult type of postural control starts to develop. As spinal transsection at P10
      abolishes their development, we hypothesize that the development of dendrite
      bundles is dependent on the ingrowth or the becoming functional of descending
      projections. On the basis of the neurophysiological and neuroanatomical results
      we conclude that the development of postural control, which reaches its final
      stage 5-6 days after the adult-like pattern of walking has developed, is
      dependent on the maturation of suprasegmental structures and their spinal
      projections.

PMID- 9595569
TI  - Head coordination as a means to assist sensory integration in learning to walk.
AB  - After a brief presentation of the development of free walking interpreted as
      learning dynamical equilibrium, the problem of sensory integration in the process
      of walking development is discussed. A critical review of the role of vision in
      the development of posturo-locomotor task is presented, along with recent test
      results on the development of the vestibular system. A final section presents the
      development of head stabilization and coordination as a necessary means to assist
      sensory integration. It is suggested that if sensory information is necessary to
      enhance posturo-locomotor skills, a good mastery of walking is in turn necessary
      to increase the efficiency of sensory integration.

PMID- 9595570
TI  - Motor development after vestibular deprivation in rats.
AB  - This review summarizes the postural development in the rat and the influences of
      vestibular deprivation from the 5th postnatal day on this development. Vestibular
      deprivation leads to a delay in motor development. Most probably this delay is
      caused by a delay in the development of postural control, which is characterized
      by a retarded EMG development in postural muscles. Our results indicate that the
      developing nervous system cannot compensate for a vestibular deficit during the
      early phase of ontogeny.

PMID- 9595571
TI  - Spasticity and 'spastic' gait in children with cerebral palsy.
AB  - The current notion of spasticity as a velocity-dependent increase of muscle
      response to imposed stretch was mainly derived from studies performed under
      stationary experimental conditions. To address the issue of a spastic muscle
      behaviour under dynamic conditions, we conceived a novel approach, aimed at
      quantitatively assessing motor output over the lengthening periods which take
      place during unperturbed functional movements. Application to the analysis of
      overground walking in children with spastic cerebral palsy (CP) revealed that,
      for representative lower limb muscles, the relationship between EMG levels and
      estimated muscle lengthening rate displays either increased gain or reduced
      velocity threshold. Parallel measurement of gait kinetics frequently showed
      congruent increase of the mechanical resistance to joint rotation. Abnormalities
      preferentially targeted the lengthening contractions occurring around the ground
      contact period of the stride. The pathophysiological profile of what is
      clinically defined as 'spastic' gait in CP children did not only consist of
      dynamic spasticity, as described above. Most often it resulted from the
      simultaneous contribution of other factors, including paresis, co-contraction,
      immature and non-neural components.

PMID- 9595572
TI  - Characteristics of locomotor control in children with cerebral palsy.
AB  - The typical features of electromyographical (EMG) recordings from children with
      cerebral palsy (CP) consist of a coactivation of antagonistic leg muscles during
      the stance phase, a low and tonic activation of extensor EMG, and enhanced
      stretch reflex excitability with short latency. This characteristic reflex
      pattern is suggested to reflect an arrested normal maturation. The strong
      similarity between the walking pattern of CP children (8-16 years of age) and the
      reflex pattern during the process of learning to walk (7-10 months of age) lets
      us draw the following conclusion. During normal maturation a close parallelism
      exists between the control of group I afferent inhibition with the suppression of
      mono/oligosynaptic stretch reflexes and group II afferent facilitation with the
      increase of polysynaptic (mainly extensor) EMG responses. This maturation depends
      on supraspinal control, and does not occur in CP children. In adult patients with
      a supraspinal lesion, a regression to this early reflex pattern takes place.

PMID- 9595573
TI  - Development of postural responses during standing in healthy children and
      children with spastic diplegia.
AB  - Studies on the development of balance control show a clear developmental
      progression of the emergence of organized muscle response patterns, with tonic
      background muscle activity decreasing and phasic bursts of activity emerging in
      all three agonist muscles in a synergic group (gastrocnemius-hamstrings-trunk
      extensors or tibialis anterior-quadriceps-abdominals) just prior to the onset of
      independent stance. The rudimentary ability to adapt postural responses to
      changing task conditions is present in children as young as 1 year of age. Older
      children with spastic diplegia have muscle activation patterns typically seen in
      normal children who are at the pull-to-stand stage of development, including
      poorly organized (proximal activated before distal muscles) responses with a high
      degree of antagonist co-activation. When normal children were asked to stand in a
      crouched posture like the CP children, the additional constraint caused muscle
      response patterns to resemble those of CP children, suggesting that differences
      in balance control in CP children are due to both CNS deficits and biomechanical
      changes in postural alignment.

PMID- 9595574
TI  - Postural control in sitting children with cerebral palsy.
AB  - Children with cerebral palsy (CP) display postural problems, largely interfering
      with daily life activities. Clarification of neural mechanisms controlling
      posture in these children could serve as a base for more successful intervention.
      Studies on postural adjustments following horizontal forward and backward
      displacements of a movable platform in ten school-age children with spastic
      diplegia and non-disabled controls revealed that sitting CP children, like
      standing CP children, show direction specific postural adjustments, indicating
      that the basic pattern of muscle coordination in these conditions is conserved.
      Dysfunctions are especially present in the modulation of the response pattern of
      ventral muscles during forward translations. They consist of: (1) a stereotyped
      and non-variable activation of all ventral muscles; (2) an abnormal top-down
      muscle recruitment; and (3) an excessive degree of antagonistic co-activation.
      The altered patterns of muscle coordination could be the result of two
      interacting mechanisms, the primary deficit due to the early brain damage and a
      compensation due to the postural instability. Especially the latter dysfunction
      furnishes opportunities for therapeutic help.

PMID- 9595575
TI  - [Adolescents and celiac disease: psychological aspects].
AB  - Many studies have been carried out on different aspects of coeliac disease in
      children and adolescents. However, little has been done on how these patients
      experience their situation and how they cope with dietary treatment. A group of
      39 children and adolescents with coeliac disease participated in a controlled
      questionnaire study. Conclusions are that the acceptance of a gluten-free diet is
      problematic for the majority of children and adolescents affected by coeliac
      disease; in particular in the 12 to 17 year old group, that is in that period of
      life in which the individual tends to oppose the adult world, in search of an
      individual personality. This search is disturbed in the majority of coeliac
      patients. The feelings of difficulty connected to the gluten-free diet appear to
      be almost absent in the family environment, whereas they emerge significantly at
      times of meeting and sharing with friends.

PMID- 9595576
TI  - [Sudden infant death syndrome (SIDS) update: etiopathogenesis, epidemiology,
      legal medicine aspects, cases].
AB  - Sudden infant death syndrome (SIDS) is the most common cause of postneonatal
      infant death in developed countries. The causes of SIDS remain unknown. The
      principal hypothesis appears abnormality of cardiorespiratory control, sleep-wake
      regulation. Also in our personal date the autopsy have not been of sufficient
      specificity and sensitivity to explain the disease.

PMID- 9595577
TI  - [Characteristics of airway colonization in mechanically ventilated newborn
      infants].
AB  - This study was designed to define the pattern of airway colonization in
      mechanically ventilated neonates and to assess whether this is associated with
      clinical signs of infection and/or local or systemic inflammation. One hundred
      and fifty-seven bronchoalveolar lavages (BAL) were obtained from 40 intubated
      neonates for microbiologic and cytologic evaluation of the distal airway.
      Concomitantly with each BAL, clinical data and laboratory tests were recorded.
      Ninety-seven BAL were negative, whilst 56 (37%) yielded the growth of gram
      positive bacteria (84%), gram-negative bacteria (6%), fungi (5%), or P. carinii
      (5%). Airway colonization occurred in 9 (22%) neonates within the first 72 hours
      of life and in 31 (78%) during the following days. S. aureus was the most
      commonly isolated organism (70%). Clinical signs of pulmonary infection were
      present in all cases of vertical colonization and in 35 (66%) of nosocomial
      transmission. Blood and BAL white cell counts were higher coincidentally with
      airway colonization (p = 0.13 and p = 0.57, respectively). Antibiotic treatment
      was changed on the basis of BAL culture results. Follow-up cultures of the BAL
      were obtained in 13 neonates in whom antibiotics were changed. Negative cultures
      were found in 8 of these neonates, and 50% of these cases showed clinical
      improvement. Further work is needed to assess the cost-benefit ratio of
      prophylactic antibiotic administration in intubated neonates and the possible
      advantage(s) of treating microorganisms colonizing the airway of these subjects.

PMID- 9595578
TI  - [Analgesic efficacy of ketorolac and fentanyl in pediatric intensive care].
AB  - OBJECTIVE: To evaluate the efficacy of the two different drugs (Ketorolac and
      Fentanyl), used singularly or in association, in the management of postoperative
      pain in Picu. STUDY DESIGN: A randomized and prospective study. METHODS: 52
      children were randomly assigned to receive intravenous Ketorolac and/or Fentanyl,
      according to four different analgesic treatments: A) Ketorolac 1.2 mg/kg every
      six hrs; B) Ketorolac 1.2 mg/kg (bolus) + 0.21 mg/ kg/hr; C) Fentanyl 1
      gamma/kg/hr; D) Fentanyl 1 gamma/kg/hr + Ketorolac 0.21 mg/kg/hr. Each protocol
      was given to 13 children. The efficacy of treatments were evaluated by child's
      behaviour (Affective Facial Scale and CHEOPS score) and hemodynamical parameters
      (systolic and diastolic blood pressure, breathing rate, heart rate, oxygen
      saturation and oxygen arterial pressure) and analysed by statistical analysis.
      RESULTS: The children treated with protocol B (Ketorolac in continuous in
      infusion) showed better pain relief in respect to those treated with protocol A
      (Ketorolac in bolus), while the most efficient analgesia was obtained with the
      association of the two analgesic drugs (protocol D). Two cases of bradycardia,
      one case of hyperazotemia and one case of transaminase increase were noted.
      CONCLUSION: Ketorolac presents a good efficient analgesia, particularly evident
      when administered in continuous intravenous infusion. However, the association of
      this NSAID with an opioid drug can be favourably proposed in postoperative pain
      therapy of moderate to severe grade, since the confirmed analgesic efficacy is
      not aggravated by important side effects.

PMID- 9595580
TI  - [Neonatal hypocalcemia: a frequent phenomenon].

PMID- 9595579
TI  - [Epidemiological and clinical findings in congenital heart diseases during the
      neonatal period. Report on personal cases].
AB  - Cardiovascular impairment is frequent in the neonatal period and can be linked to
      malformative and non malformative pathologies. The Authors performed a
      retrospective study on the incidence of these two types of pathologies in a
      population of 3326 newborns who underwent cardiological examination. Malformative
      cardiopathy was observed in 779 (23.4%) of them, while non malformative
      cardiopathy was present in 316 (9.5%). Acyanogen forms (86.7%) were more common
      than cyanogen forms (13.2%) in malformative, while cyanogen forms (64.8%) were
      more frequent than acyanogen ones (35.1%) in non malformative cardiopathies. The
      Authors reviewed the incidence of the single cardiac defects and report some
      clinical and physiopathological considerations that underline the need for prompt
      differential diagnosis and the validity of echocardiography in achieving this
      aim.

PMID- 9595581
TI  - [Prevalence of hepatitis A antibodies in polytransfused thalassemic patients].
AB  - Chronic liver disease in polytransfused thalassemic patients is an important
      cause of morbidity and mortality. The genesis is multiform: haemosiderosis and
      virus infections, resulting from repeated transfusions, may play an important
      role. Since HAV infection could make greatly worse the prognosis, in order to
      evaluate the opportunity of the HAV vaccination in polytransfused thalassemic
      patients, we studied the prevalence of HAV infection by detection of anti HAV
      antibodies (IgG) (enzyme immunoassay competitive technique) in 75 thalassemic
      patients (36 males, 39 females, aged 21.1 +/- 9.6, mean +/- SD). Fourty-two
      patients (56%) were HCV positive with persistent increase of transaminases. Eight
      patients were HAV antibodies positive (10.6%); the prevalence was 2.7% in
      patients aged 1 to 19 years, 11.4% in patients aged 20-39 years and 100% over 40
      years of age. No differences were observed between sexes. Five out of fourty-two
      patients HCV positive were HAV antibodies positive (11.9%). In conclusion, in
      order to reduce further the incidence of liver infections in polytransfused
      thalassemic patients, we recommend an active immunization for HAV.

PMID- 9595582
TI  - [Visceral leishmaniasis in children in the province of Florence].
AB  - Three cases of visceral leishmaniasis are presented: two children who got the
      disease in Florence and the imported case of a girl coming from Albania with her
      disease in act. The diagnosis was made showing Leishmania in bone marrow
      specimen. Therapy with melglumine antimonate was effective and well borne,
      leading the three children to a complete healing. In the province of Florence
      visceral leishmaniasis is very rare, but such protozoa and the sand flies are
      present as shown by the high number of dog with leishmaniasis.

PMID- 9595584
TI  - [Cryptorchidism: a study of histological changes in undescended testis related to
      age].
AB  - A total of 46 testicular biopsies were examined to define the histological
      characteristics of undescended testicle. Nine of the biopsied organs were
      normally positioned testicles from deceased pediatric patients (aged 2 months-14
      years), and the remaining 37 were undescended testes from children with various
      degrees of cryptorchidism (aged 18 months-14 years). As reported by others, the
      degree of histological damage was directly proportional to the age of the
      subject. Close correlation between histological findings and the level of descent
      was not observed.

PMID- 9595583
TI  - [Blood sugar control in children and young diabetics during an educational summer
      camp].
AB  - The aim of the study was to evaluate the impact of educative summer camp on the
      glycemic control in two different age-groups of young diabetic patients. METHODS:
      54 patients (36 M, 18 F, age 10-27 years, duration of diabetes 2-19 years),
      treated with 0.81 +/- 0.2 UI/kg/day of insulin and with HbA1c mean levels of 8.25
      +/- 1.35 g% were followed by an equip of 8 medical doctors, 4 nurses and 1
      dietician for a week during an educative summer camp. RESULTS: 34 children, group
      1 (20 M, 14 F, 10-14 years aged, mean duration of the disease 4.52 years, range 2
      12 years) and 20 young adults, group 2 (16 M, 4 F, age 16-27 years, mean duration
      10.21 years, range 2-19 years) were evaluated. Insulin doses and HbA1c levels
      were 0.82 +/- 0.21 UI/kg/day vs 0.80 +/- 0.22 U/kg/day and 9.54 +/- 1.5% vs 7.6
      +/- 0.6%, p < 0.02 in group 1 and 2 respectively. Glycemic levels at 8 a.m. and
      11 p.m. were significantly higher in group 1 than in group 2 (180 +/- 87 mg% vs
      219 +/- 77 mg%, p < 0.05 and 164 +/- 84 mg% vs 201 +/- 81 mg%, p < 0.05).
      Hypoglycemic/patient/episodes were 1.82 vs 0.72, p < 0.05 in group 1 and group 2
      respectively. CONCLUSIONS: 1. Glycemic control was unsatisfactory in both groups
      and it was significantly worse in the group of youngs, though in this group HbA1c
      level was significantly lower. 2. The risk of hypoglycemia was significantly
      higher in group 1, though in this group insulin doses were significantly
      decreased.

PMID- 9595585
TI  - [Vertebral schisis in enuretic children: preliminary results of a statistical
      analysis].
AB  - It is well known that vertebral schisis is frequent in enuretic children but the
      true incidence in the normal population is not clear, because all series
      published are referred to children with associated urinary anomalies, who were
      submitted to voiding cystography and or intravenous pyelography. This determine a
      statistical bias. The aim of our study was to compare the prevalence of vertebral
      schisis in enuretic children and in the general pediatric population. Therefore,
      we chose 142 enuretic children without associated urological or neurological
      anomalies and a control group of 152 children, assumed as general population, who
      were submitted to spinal X-rays during screening for scoliosis or congenital
      dysplasia of the hip. Vertebral schisis was found in 65% (93/142) of enuretics
      and in 18% (28/152) of control group children. Maximum association between
      enuresis and vertebral schisis was found in primary monosymptomatic nocturnal
      enuresis (82%), while minimum association was found in children with secondary
      enuresis (57%). The difference in percentage of association enuresis-schisis was
      statistically significant between enuretics and control group and between primary
      monosymptomatic and secondary enuresis (p < 0.001). The results of this paper are
      simply add knowledges on the prevalence of the sacral schisis in enuretic
      children. But, to speculate the different prevalence in different types of
      enuresis, the results should confirm that the phenomenon of enuresis is
      multifactorial and the primary monosymptomatic and secondary enuresis have
      different etiological factor.

PMID- 9595586
TI  - [Study of the reliability of a parenteral questionnaire used in a pediatric
      follow-up of 18-month-old children].
AB  - We are conducting a validation study of questionnaire to the parents according to
      the Griffiths Mental Developmental Scale, used in pediatric follow-up of
      obstetric studies among the Italian population. The questionnaire concerns the
      child's gross and fine motor and language development, swallowing, respiratory,
      hearing and vision problems, and hospital admissions within the first 18 months
      of life. The purpose of this study is to examine the degree of agreement between
      parental and professional assessment of normal and high-risk infants development
      at 18 months of life.

PMID- 9595587
TI  - [Pseudotumor cerebri: a pediatric case report].
AB  - We describe a case of pseudotumor cerebri (PTC) in a five years old child.
      Pseudotumor cerebri is a not very common syndrome in the pediatric age. The
      incidence rate in about 1:100.000. The prognosis of PTC is usually good.
      Sometimes however, PTC could be complicated by eye diseases such as reduction of
      visual field. Our case is a child with diplopia and with a bilateral oedema of
      the papilla. The diagnosis of PTC was possible after the physical examination and
      the instrumental exams (EEG, brain NMR and others). During the staying in the
      hospital the child performed a therapy with betamethasone and acetazolamide; the
      diplopia improved and the bilateral oedema of the papilla started to be less
      evident. The child was discharged in good health and with a planned ocular follow
      up. We think that the Pediatrician must considered the possibility of the
      presence of a PTC; that is an important syndrome not only for the Neurologist.

PMID- 9595588
TI  - Schonlein-Henoch vasculitis and chronic Helicobacter pylori associated gastritis
      and duodenal ulcer: a case report.
AB  - We describe the case of a child with Schonlein-Henoch purpura (SHP), bleeding
      duodenal ulcer and Helicobacter pylori (H. pylori) associated gastritis. 5-year
      old girl was hospitalized with typical symptoms of SHP. On the third day, the
      child has several episodes of hematemesis with bright red blood, accompanied by
      increased pain of the epigastric region. Gastroduodenal endoscopy revealed signs
      of atrophic gastritis in the antrum, duodenitis with diffuse petechiae, small
      erosions and bleeding ulcer. The gastric biopsy showed a moderately severe
      chronic gastritis with activity and H. pylori was detected. The therapy with
      ranitidine, metronidazole and amoxycillin was introduced for a period of 30 days.
      At follow-up 2 months later, clinical examination and routine laboratory tests
      were normal. A repeated endoscopy revealed no evidence of lesions and H. pylori
      negative gastric biopsy. In our case, the associated chronic antral gastritis and
      H. pylori infection may well have aggravated the gastrointestinal symptoms of
      SHP. We feel it would be useful to check for H. pylori in patients with
      gastrointestinal manifestations of SHP, such as bleeding and important epigastric
      pain.

PMID- 9595589
TI  - [CHARGE association: report of a clinical case with anal atresia and rectovaginal
      fistula].
AB  - CHARGE association is a non-random constellation of Coloboma, Heart Disease,
      Atresia of the choana, Retarded mental development and growth, Genital
      hypoplasia, Ear anomalies and deafness. We report on a newborn with CHARGE
      association. In addition to the typical features our case presented anal atresia
      and rectovaginal fistula. Our patient had congenital cardiopathy and feeding
      problems and died at the age of 3 months. Most case of CHARGE association appear
      to have a primary defect of pharyngeal incoordination that cause aspiration of
      secretion that is an important cause of death in the nonsurvivors.

PMID- 9595590
TI  - [Rhabdoid tumor of the kidney: a rare malignant neoplasm of infancy. A case
      report and review of the literature].
AB  - Rhabdoid tumor of the kidney (RTK) is a quite rare malignant neoplasm of early
      childhood. It has a very unfavourable prognosis, since it tends to give early
      metastases and shows a poor response to chemotherapy regimens. We report a case
      of an infant with RTK, who had a rapidly progressive course. Based upon our case
      and the review of the literature, we would like to stress the importance of a
      differential diagnosis with another kidney cancer, namely Wilms tumor, which is
      more frequent and has by far a better prognosis.

PMID- 9595591
TI  - Interpersonal interactions in individuals with schizophrenia: individual
      differences among patients and their partners.
AB  - We examined 60 face-to-face ten-minute interactions between individuals with
      schizophrenia and college students. We studied patient responses to the students
      and student responses to the patients. Following each interaction, participants
      provided reports of their current mood and how well they liked their interaction
      partner. The interactions were audio- and video-taped, which allowed us to
      measure the frequency of patient and student smiles and eye contact, patient
      strangeness, and the pleasantness of the conversational content. We found
      individual differences among patients in the degree to which they were liked by
      students. Patient strangeness was associated with interaction partner negative
      responses to patients. In addition, the pleasantness of the conversational
      content was associated with how well patient and student were liked by one
      another. Sixteen percent of the variance in patient smiling was accounted for by
      the particular student with whom the patient interacted. The results of this
      study highlight the importance of attending to both intrapersonal and
      interactional factors for understanding patient interpersonal functioning.

PMID- 9595592
TI  - Description of mothers with ADHD with children with ADHD.
AB  - Pilot data demonstrating the personality traits and background variables of ADHD
      mothers with children with ADHD are presented. Three subject groups are compared:
      mothers with ADHD, with ADHD children; mother without ADHD, with ADHD children;
      and mothers without ADHD, without ADHD children. Significant differences are
      observed on the Wender Utah Scale for attention deficit disorder, levels of
      neuroticism and conscientiousness on the NEO-Five Factor Inventory are
      significantly higher in mothers with ADHD. In addition, neuropsychiatric
      disorders, alcoholism in the family of origin, and atypical sexual events are
      reported at a significantly higher rate in the mothers with ADHD, with ADHD
      children. The implications of group differences are discussed.

PMID- 9595593
TI  - "Full recovery" from schizophrenia in the long term: a ten-year follow-up of
      eight former schizophrenic patients.
AB  - The present study reports longitudinal data on individuals who ten years ago were
      fully recovered from a previously diagnosed schizophrenia. Seven out of ten
      subjects consented and were reexamined at the present follow-up, and data on an
      eighth subject was secured elsewhere. A semistructured interview was used to
      examine psychosocial functioning of the subjects in the follow-up period. Out of
      the six subjects with a confirmed diagnosis of schizophrenia, only three subjects
      were still fully recovered; one had a deteriorating course and two had a
      fluctuating course of illness. The results from the study indicate that recovery
      from schizophrenia may take the form of time-limited remissions for half of the
      reexamined subjects when strict criteria for full recovery are used. Protective
      factors such as willpower, a (partly) intact capacity for object attachment, and
      a supportive family may be important prerequisites for recovery. Two different
      courses of schizophrenia are illustrated by cases.

PMID- 9595594
TI  - Symptom study in context: effects of marital quality on signs of Parkinson's
      disease during patient-spouse interaction.
AB  - Hypokinesia, the inability to initiate or maintain movement, represents one of
      the most disabling aspects of Parkinson's disease (PD), and displays intriguing
      moment-to-moment variability from environmental stressors. Correlates of
      orofacial hypokinesia (characteristics of spontaneous eye blink and speech) were
      coded from videotaped interactions for PD patients in maritally distressed and
      nondistressed dyads. Significant changes occurred only for the patients in
      distressed relationships on the two strongest neurophysiologic measures of
      orofacial hypokinesia, rate and duration of spontaneous eye blink. Further
      analyses suggest two possible explanations for these temporal symptom changes.
      Distressed spouses may exacerbate symptoms by exposing the patient to negativity.
      Alternately, nondistressed spouses may compensate for the demands of the
      interactional task by assuming a greater share of the conversation relative to
      the patient's contribution. Results are linked to existing literature; the role
      of social and familial support in chronic illness is discussed.

PMID- 9595595
TI  - Information gating: an evolutionary model of personality function and
      dysfunction.
AB  - Utilizing principles of evolutionary biology, a model is developed which defines
      the essential adaptive functions of personality as a whole, and describes how
      failure in those functions produces the maladaptations characteristic of
      personality disorders. In this model, personality is hypothesized to have evolved
      specifically to make human culture possible by managing the flow of information
      within the culture, especially by mediating teaching and learning, competition
      and cooperation, and leading and following. These essential culture-forming
      capacities of personality have at their root the more basic function of
      information gating, which is defined here as the continuous regulation by
      personality of its openness for the bidirectional flow of sensory, cognitive,
      emotional, and motor information between internal self and external social
      systems, to best meet the needs of both in various situations. The maladaptations
      characteristic of personality disorders are postulated to be due to their being
      chronically and frequently too open or too closed for expressing or assimilating
      social information, given their circumstances. The relationship of this model to
      other evolutionary models of personality is discussed, as are its clinical and
      research implications.

PMID- 9595597
TI  - Science and ideology in psychoanalysis and male homosexuality: more and less than
      meets the eye.

PMID- 9595596
TI  - Reconstructing silenced biographical issues through feeling-facts.
AB  - The undiscussible within daily discourse can have intentional and unintentional
      forms. The first occurs when someone intentionally gears the discourse so that it
      will not reveal certain facts which have happened (such as being an abused child,
      or a perpetrator during the Holocaust). We assume that even if they were
      difficult to reconstruct as part of one's biography, these facts could be
      verified externally (not only through the feelings of the victim). In the first
      part of the paper, we analyze the paradoxical nature of such discourse, and show
      how difficult it is to work through intentional undiscussibility. In the second
      part, we discuss what happens when the undiscussible facts can not be verified,
      meaning that there is doubt if events have taken place. By presenting a case
      study of a German woman who tried to construct a biography in face of certain
      undiscussibility in her family, we discuss the different social reactions
      evolving in such reconstruction of feeling-facts. We thereby hope to confront the
      psychoanalytic approach to narrative analysis with the constructivist hermeneutic
      one.

PMID- 9595598
TI  - Development of analogues: successes and failures.
AB  - The search for new pharmaceutical treatments has led to the isolation of products
      from a range of natural sources. Analogues synthesized from these products may
      possess an improved therapeutic effect over their natural counterparts. Two
      natural peptides, vasopressin and somatostatin, possess pronounced in vivo
      effects, so do their analogues terlipressin and octreotide. Vasopressin is a
      powerful vasopressor, reducing portal pressure, and has been used to treat
      gastrointestinal haemorrhages. However, a number of adverse cardiovascular
      effects resulting from an increase in peripheral vascular resistance have been
      associated with this drug. Terlipressin, however, is more effective, has an
      improved safety profile and is associated with fewer side effects than
      vasopressin. Somatostatin, a growth regulatory hormone, achieves haemostasis by
      decreasing splanchnic blood flow, and is effective in preventing early
      rebleeding. Somatostatin is effective in treating bleeding oesophageal varices
      (BOV) and is associated with fewer and more transient side effects than
      terlipressin. Octreotide, however, has greater stability and a longer half-life
      than somatostatin, but has a less favourable safety profile. Octreotide displays
      a number of therapeutic advantages over somatostatin, but not in the treatment of
      gastrointestinal indications. The development of terlipressin from vasopressin
      has demonstrated a number of clinical advantages, while the development of
      octreotide from somatostatin has not shown any significant advantage in the
      treatment of BOV.

PMID- 9595599
TI  - Optimizing emergency care of upper gastrointestinal bleeding in cirrhotic
      patients.
AB  - The type of emergency treatment administered to patients with suspected variceal
      bleeding is important, as the episode is associated with a high mortality rate.
      Moreover, rebleeding is common during the first few days after the initial
      haemorrhage. Several techniques are available to control variceal haemorrhage
      including pharmacotherapy (vasopressin, terlipressin, somatostatin and
      octreotide), balloon tamponade, endoscopic techniques, transjugular intrahepatic
      portosystemic shunt and shunt surgery. The majority of these require specialized
      equipment and/or experienced personnel, which are not always available in every
      hospital. In such situations, pharmacotherapy represents the most practical
      method of establishing haemodynamic control prior to the administration of
      definitive treatment. Pharmacotherapy can be initiated immediately upon admission
      to stabilize the patient prior to diagnostic endoscopy, which subsequently
      improves the efficacy and ease of administration of further endoscopic
      intervention. The optimal pharmacological agent should be both effective and
      safe. A drug with no side effects will not complicate the management of critical
      patients and can be administered over an extended period to reduce the incidence
      of rebleeding and improve prognosis. Meta-analysis of clinical studies has
      revealed that of the vasoactive drugs available somatostatin is effective with
      significantly fewer side effects and currently appears to represent the best
      choice for treatment. The available evidence suggests that the early
      administration of pharmacotherapy, as part of a specific treatment regimen,
      offers significant benefit to patients with variceal bleeding and its
      administration optimizes emergency care.

PMID- 9595600
TI  - Emergency endoscopy strategies for improved outcomes.
AB  - Variceal haemorrhage is the most serious complication of portal hypertension and
      is associated with a high mortality rate. The first stage of treatment is to
      stabilize the patient, followed by emergency diagnostic endoscopy to identify the
      source of the bleeding. If active variceal bleeding is found, endoscopic
      intervention is performed to induce haemostasis. The endoscopic techniques
      commonly used to treat bleeding gastro-oesophageal varices include injection
      sclerotherapy and band ligation. Sclerotherapy achieves haemostasis through the
      induction of thrombosis or by external compression of the vessel and should be
      performed during diagnostic endoscopy. Band ligation achieves haemostasis by
      physical constriction of the varix. Band ligation may be less effective than
      sclerotherapy in the treatment of actively bleeding oesophageal varices and is
      therefore recommended for subsequent elective treatment of non-bleeding varices.
      However, such techniques are difficult to perform during active bleeding. This
      has prompted the search for improved treatment protocols. Vasoactive drugs which
      lower portal hypertension have been administered before, during and after
      endoscopy and may offer an improvement in treatment. Data from several trials
      have suggested that pharmacotherapy in combination with endoscopic intervention
      is more effective than endoscopic treatment alone. Furthermore, pharmacotherapy
      continued for 5 days following endoscopy significantly reduces the incidence of
      variceal rebleeding. A strict regimen for emergency endoscopy should be used with
      sclerotherapy forming the basis of treatment--administered in combination with
      pharmacotherapy, to optimize clinical outcome. However, there is still debate
      concerning what is the most effective drug for treating variceal haemorrhage.

PMID- 9595601
TI  - The Taskforce 2000 survey on medical education in sleep and sleep disorders.
AB  - Previous research has shown evidence of a widening gap between scientific
      research and clinical teaching in sleep and sleep disorders. To address the
      deficiencies in current medical education in sleep, the Taskforce 2000 was
      established by the American Sleep Disorders Association. The present study was
      undertaken to assess the teaching activities, needs and interests of the
      membership of the two largest professional sleep societies (American Sleep
      Disorders Association and Sleep Research Society). Survey instruments included a
      brief, 5-item postcard survey, which was mailed to all members, followed by an in
      depth, 34-item questionnaire, which was completed by 158 respondents from the
      intitial postcard survey (N = 808). Results indicated that the majority of
      respondents (65.2%) are currently involved in teaching sleep to medical students
      or postgraduate trainees, although the average amount of teaching time was only
      2.1 hours for undergraduate and 4.8 hours for graduate education in sleep.
      Teaching of sleep laboratory procedures and clinical evaluation of sleep
      disordered patients is limited at either an undergraduate or postgraduate level.
      The major deficiencies noted were the lack of time in the medical curriculum and
      the need for better resources and teaching facilities. A large majority of
      respondents indicated their willingness to be involved in sleep education for
      physicians, and rated this a high priority for the professional organization.

PMID- 9595602
TI  - Effects of short-term sleep deprivation on murine immunity to influenza virus in
      young adult and senescent mice.
AB  - Sleep has been proposed as an innate host defense, exerting effects on both
      specific and nonspecific immunity. In one of the more striking papers dealing
      with the effects of sleep on specific immunity, Brown et al (Reg. Immunol. 1989;
      2: 321-325) reported that depriving influenza virus-immune mice of sleep for 7
      hours following total respiratory tract viral challenge abrogated anti-viral
      immunity within the lungs and lowered the level of anti-influenza antibody in
      lung homogenates. In the solidly-immune convalescent mouse, nasobronchial
      immunity to influenza virus has been shown to be due to secretory IgA (S-IgA)
      within the mucosal mucocilliary blanket, while serum IgG has been shown to
      mediate protection within the lung parenchyma. In this study we attempted to
      duplicate the work of Brown et al in solidly immune mice. We were unable to
      abrogate mucosal anti-influenza viral immunity with a single post-viral-challenge
      sleep-deprivation episode, nor were we able to depress this immunity with one pre
      and two post-challenge sleep-deprivation episodes in young adult or old mice, or
      with two pre-challenge sleep-deprivation episodes in old mice. Sleep deprivation
      did not depress the level of serum influenza-specific IgG antibodies, and
      resulted in increased influenza-specific serum IgG compared with normally
      sleeping mice in aged immune mice boosted 3 weeks before challenge and sleep
      deprived once before and twice after challenge (p = 0.005). No differences in
      anti-viral respiratory immunity were apparent between young and old mice. We
      conclude that short-term sleep deprivation has minimal effects on pre-existing
      mucosal and humoral immunity in either the young adult or the senescent mouse.

PMID- 9595603
TI  - Starting times of school: effects on daytime functioning of fifth-grade children
      in Israel.
AB  - In the present study we investigated the effects of school starting time on
      daytime behavior and sleep. Eight-hundred and eleven 5th grade pupils (10-12
      years old) from 28 classes in 18 schools throughout Israel were divided into
      "early risers" (N = 232) who started school at 07:10 (42%) at least 2 times a
      week, and "regular risers" (N = 340) who always started school at 08:00 (58%).
      The remaining 239 pupils started school between 7:20 and 07:55 (and also after
      08:00), and were not included in the study. Self-administered questionnaires
      concerning sleep habits during school days, weekends, and holidays, daytime
      fatigue, sleepiness, and difficulties concentrating and paying attention in
      school were completed by all children. Mean sleep time of the "early risers" was
      significantly shorter than that of the "regular risers." Early risers complained
      significantly more about daytime fatigue and sleepiness, and about attention and
      concentration difficulties in school. Their complaints were independent of the
      reported hours of sleep. We conclude that early starting of school negatively
      affects total sleep time and, as a consequence, has a negative effect on daytime
      behavior. The implications of these findings to the ongoing controversy
      concerning sleep need in contemporary society are discussed.

PMID- 9595604
TI  - Pupillographic assessment of sleepiness in sleep-deprived healthy subjects.
AB  - Spontaneous pupillary-behavior in darkness provides information about a subject's
      level of sleepiness. In the present work, pupil measurements in complete darkness
      and quiet have been recorded continuously over 11-minute period with infrared
      video pupillography at 25 Hz. The data have been analyzed to yield three
      parameters describing pupil behavior; the power of diameter variation at
      frequencies below 0.8 Hz (slow changes in pupil size), the pupillary unrest
      index, and the average pupil size. To investigate the changes of these parameters
      in sleep deprivation, spontaneous pupillary behavior in darkness was recorded
      every 2 hours in 13 healthy subjects from 19:00 to 07:00 during forced
      wakefulness. On each occasion, comparative subjective sleepiness was assessed
      with a self-rating scale (Stanford Sleepiness Scale, SSS). The power of slow
      pupillary oscillations (< or = 0.8 Hz) increased significantly and so did the
      values of SSS, while basic pupil diameter decreased significantly. Slow pupillary
      oscillations and SSS did not correlate well in general but high values of pupil
      parameters were always associated with high values in subjective rating. Our
      results demonstrate a strong relationship between ongoing sleep deprivation and
      typical changes in the frequency profiles of spontaneous pupillary oscillations
      and the tendency to instability in pupil size in normals. These findings suggest
      that the results of pupil data analysis permit an objective measurement of
      sleepiness.

PMID- 9595605
TI  - Homeostatic regulation of REM sleep in humans during extended sleep.
AB  - Benington and Heller (1994) recently proposed a sleep-dependent model for the
      homeostatic control of REM sleep in which the amount of REM sleep propensity
      discharged in each bout of REM sleep affects the timing of the subsequent REM
      episode. Consistent with their hypothesis, they reported that in rats the
      duration of a REM episode was positively correlated with the duration of the
      succeeding NREM episode and not with the duration of the preceding NREM episode.
      To assess this hypothesis in humans, we used 308 sleep records from 11 subjects
      who remained at bedrest in the dark and slept ad libitum during 14-hour periods
      each night for 4 weeks. The timing of the onset of the first REM episode of the
      long night was linked to the timing of sleep onset. NREM-REM cycle duration
      decreased progressively throughout the night as a result of a progressive
      decrease in duration of the NREM component. Durations of REM sleep episodes
      correlated significantly with durations of subsequent NREM episodes in three out
      of the eight rank cycles analyzed (p < .0031, Bonferroni corrected); positive
      correlation coefficients were found for all the remaining cycles, but were not
      statistically significant when the conservative Bonferroni correction of the
      alpha level was applied. With the exception of the first sleep cycle, durations
      of REM sleep episodes did not correlate with durations of preceding NREM sleep
      episodes. According to the present results, the amount of REM sleep in one
      episode controls the time of occurrence of the next REM episode when the impact
      of other possible regulating factors are at a low level. We hypothesize that the
      extended dark/rest period, by increasing the time window allowed for sleep,
      provided a condition under which the systems governing REM sleep expression were
      free of the masking imposed by the conventional 16 hours light/8 hours dark
      schedule that consolidates and compresses sleep.

PMID- 9595607
TI  - Colonic motor activity in women during sleep.
AB  - The relationship between colonic motility, sleep, and arousals from sleep has
      never been studied in women and only once in men. The purpose of this study was
      to determine how sleep and arousals from sleep affected colonic motility in women
      during the follicular phase of their menstrual cycle. We monitored sleep and
      segmental colonic motility in six healthy women during the follicular phase of
      the menstrual cycle. We observed no colonic motility during sleep; during awake
      periods or during arousals, we observed isolated low-amplitude bursts of colonic
      motility. This colonic motility occurred during 25% of the arousal and awakening
      time. In contrast, morning awakening was associated with high-amplitude
      independent and related colonic motility in all colonic segments. We conclude
      that in women in the follicular phase of their menstrual cycle, colonic motility
      is inhibited during sleep; colonic motility at night only occurs during arousals
      or awakenings from sleep.

PMID- 9595606
TI  - Endocrinological and polysomnographic findings in Kleine-Levin syndrome: no
      evidence for hypothalamic and circadian dysfunction.
AB  - Five subjects--four men, ages 17-28, and one woman, age 30--with Kleine-Levin
      syndrome were investigated during symptomatic (SP) and asymptomatic (ASP)
      periods. Investigations comprised medical history, MRI, polysomnography, 24-hour
      hormone profile of human growth hormone, melatonin, TSH, cortisol and FSH (in the
      woman only) assessed every 2 hours, actimetry, and sleep logs. Medical history
      confirmed presence of the three symptoms diagnostic of of typical Kleine-Levin
      syndrome: hypersomnia, excessive food intake, and psychic alteration. MRIs of the
      brain were normal in all patients. Symptomatic periods were triggered by
      unspecific events, such as infection, sleep deprivation, and alcohol.
      Polysomnography revealed low sleep efficiency during SPs, decreased amount of
      slow-wave sleep, and high frequency of stage shifts, indicating sleep
      fragmentation. Mean 24-hour growth hormone levels were reduced during the SPs in
      only two patients. Their hGH peaks were dissociated from slow-wave sleep during
      attacks and intervals, often occurring during wake time. Twenty-four-hour
      melatonin levels were increased during the SPs in all patients, but were lower in
      two patients during the nocturnal sleep period. Cortisol, TSH and FSH did not
      reveal important differences between attacks and intervals. Except for hGH, all
      hormones had normal circadian excretion during symptomatic and asymptomatic
      periods. Amplitude of nocturnal activity as assessed by actimetry was
      significantly increased in two patients, whereas amplitude of daytime activity
      was significantly reduced in three patients. Actimetry and sleep logs
      demonstrated prolonged sleep phases during SPs. Our investigation could confirm
      changes of sleep structure described in the literature. The neuroendocrinological
      findings could not confirm decreased hGH and cortisol and increased TSH levels
      during SPs, as previously reported in single cases by many authors.
      Endocrinological findings did not support an underlying circadian disorder in
      KLS.

PMID- 9595608
TI  - Susceptibility of LDL to oxidative stress in obstructive sleep apnea.
AB  - Cardiovascular diseases are more common in patients with obstructive sleep apnea
      (OSA) than in the general population. We hypothesized that severe hypoxemia
      during sleep in these patients may cause an imbalance between reactive oxygen
      species and the antioxidant reserve that is important for the detoxification of
      these molecules. We tested the hypothesis that low-density lipoproteins (LDL) in
      hypoxic OSA patients may be more susceptible to oxidative stress than LDL of
      nonhypoxic OSA patients and normal controls. Fifteen OSA patients were included
      in this study, six with severe hypoxia (hypoxic group) who spent more than 10
      minutes during sleep with SaO2 < 85% (mean 96 minutes), and nine OSA patients
      (nonhypoxic group) who spent less than 10 minutes during sleep with SaO2 < 85%
      (mean 1.1 minutes). Six healthy nonsmoking males of the same age group were
      included as a control group. The susceptibility of each individual's LDL to
      oxidative stress was examined after free-radical challenge in vitro by assessing
      changes in levels of conjugated dienes. The LDL in OSA patients with severe
      hypoxia was not more susceptible to oxidative stress compared to the LDL of
      nonhypoxic OSA patients and normal controls. After 6 hours of exposure to an
      oxidative agent, the changes in the mean conjugated diene were not different
      among the three groups (p = 0.75). The time required to reach 50% of maximal
      absorbance was also not different, p = 0.199. Glutathione peroxidase and catalase
      activities in red blood cells in the hypoxic and nonhypoxic patient groups were
      not significantly different. One night of CPAP therapy in each patient group did
      not significantly change the level of the antioxidant enzymes. Our results did
      not show any difference in the susceptibility to oxidative stress between hypoxic
      and nonhypoxic OSA patients and normal controls.

PMID- 9595609
TI  - Obstructive sleep apnea syndrome in a family with Crouzon's syndrome.
AB  - Craniofacial anomalies are recognized causes of obstructive sleep apnea syndrome
      (OSAS) in children. Current literature is limited due to rarity of cases.
      Furthermore, the mechanism of upper airway obstruction is not clearly understood.
      We would like to report a family (father and 2 sons) who are suffering from
      Crouzon's syndrome. The two brothers (ages 1 and 3) were found to have
      significant obstructive sleep apnea syndrome (OSAS) with failure to thrive. Nasal
      continuous positive airway pressure (CPAP) markedly improved their OSAS and
      resulted in accelerated weight gain. The nasoendoscopy and magnetic resonance
      imaging (MRI) scan taken during natural sleep showed that choanal stenosis,
      maxillary hypoplasia, posteriorly displaced tongue, lengthened soft palate and
      adenoid tissues were important in the pathogenesis of upper airways obstruction
      in Crouzon's syndrome. Nasal CPAP improved airway obstruction by opening a narrow
      slit as demonstrated by MRI. Our results suggest that OSAS occurred in children
      with Crouzon's syndrome and that nasal CPAP was a useful treatment modality.

PMID- 9595610
TI  - Sleep states and neonatal pulse oximetry.
AB  - AIM: Pulse oximetry is a quick, easy, noninvasive method widely used for
      monitoring oxygen saturation (SaO2) in the neonatal period. The greatest
      recognized problem with SaO2 readings measured from the oximeter is artifact,
      arising from an inability to record accurately during movement. The aim of this
      study was to determine the proportion of pulse oximeter readings affected by
      movement artifact during sleep in term and preterm infants. METHOD: Polygraphic
      recordings were obtained from 11 term and 6 preterm infants at postconceptional
      ages (SD) of 39.8 (0.8) and 39.3 (1.5) weeks respectively. The polygraphic and
      computer recordings were divided into epochs of 30 seconds duration and
      identified as active sleep (AS), quiet sleep (QS), indeterminate sleep (IS), or
      wakefulness (AW), using electrophysiological parameters and behavioral
      observations. Movement artifact was identified by visual examination of
      polygraphic computer recordings using strict criteria. Signal containing artifact
      was removed from recordings and the percentage of artifact time present per
      recording calculated. RESULTS: Signal artifact was present in recordings of all
      infants studied, comprising an average state time of 19% during quiet sleep, 49%
      of active sleep, 49% of indeterminate sleep and 91% of wakefulness. A significant
      difference in the proportion of artifact present in recordings of term and
      preterm was observed only during quiet sleep. CONCLUSION: Movement artifact
      during pulse oximetry recordings is dependent on behavioral state, and overall
      affects up to 50% of recorded traces. A reliable and more accurate noninvasive
      method of recording oxygen saturation is thus needed, for use in both neonatal
      nurseries and in sleep studies, to aid in accurate clinical decision-making.

PMID- 9595611
TI  - Bibliography of recent literature in sleep research.

PMID- 9595612
TI  - Kappa-like indices of observer agreement viewed from a latent class perspective.
AB  - It is common practice to assess consistency of diagnostic ratings in terms of
      'agreement beyond chance'. To explore the interpretation of such a term we
      consider relevant statistical techniques such as Cohen's kappa and log-linear
      models for agreement on nominal ratings. We relate these approaches to a special
      latent class concept that decomposes observed ratings into a class of
      systematically consistent and a class of fortuitous ratings. This decomposition
      provides a common framework in which the specific premises of Cohen's kappa and
      of log-linear models can be identified and put into perspective. As a result it
      is shown that Cohen's kappa may be an inadequate and biased index of chance
      corrected agreement in studies of intra-observer as well as inter-observer
      consistency. We suggest a more critical use and interpretation of measures
      gauging observer reliability by the amount of agreement beyond chance.

PMID- 9595613
TI  - A generalized F mixture model for cure rate estimation.
AB  - Cure rate estimation is an important issue in clinical trials for diseases such
      as lymphoma and breast cancer and mixture models are the main statistical
      methods. In the last decade, mixture models under different distributions, such
      as exponential, Weibull, log-normal and Gompertz, have been discussed and used.
      However, these models involve stronger distributional assumptions than is
      desirable and inferences may not be robust to departures from these assumptions.
      In this paper, a mixture model is proposed using the generalized F distribution
      family. Although this family is seldom used because of computational
      difficulties, it has the advantage of being very flexible and including many
      commonly used distributions as special cases. The generalised F mixture model can
      relax the usual stronger distributional assumptions and allow the analyst to
      uncover structure in the data that might otherwise have been missed. This is
      illustrated by fitting the model to data from large-scale clinical trials with
      long follow-up of lymphoma patients. Computational problems with the model and
      model selection methods are discussed. Comparison of maximum likelihood estimates
      with those obtained from mixture models under other distributions are included.

PMID- 9595614
TI  - Modelling cure rates using the Gompertz model with covariate information.
AB  - We extend the modified Gompertz hazard function, first used by Cantor and Shuster
      for estimation of cure rates from pediatric clinical trials, by including
      covariate effects. The extended model provides a convenient method for estimation
      of the cure rate as a function of treatments and covariates.

PMID- 9595615
TI  - Detecting and describing heterogeneity in meta-analysis.
AB  - The investigation of heterogeneity is a crucial part of any meta-analysis. While
      it has been stated that the test for heterogeneity has low power, this has not
      been well quantified. Moreover the assumptions of normality implicit in the
      standard methods of meta-analysis are often not scrutinized in practice. Here we
      simulate how the power of the test for heterogeneity depends on the number of
      studies included, the total information (that is total weight or inverse
      variance) available and the distribution of weights among the different studies.
      We show that the power increases with the total information available rather than
      simply the number of studies, and that it is substantially lowered if, as is
      quite common in practice, one study comprises a large proportion of the total
      information. We also describe normal plots that are useful in assessing whether
      the data conform to a fixed effect or random effects model, together with
      appropriate tests, and give an application to the analysis of a multi-centre
      trial of blood pressure reduction. We conclude that the test of heterogeneity
      should not be the sole determinant of model choice in meta-analysis, and
      inspection of relevant normal plots, as well as clinical insight, may be more
      relevant to both the investigation and modelling of heterogeneity.

PMID- 9595616
TI  - Two-sided confidence intervals for the single proportion: comparison of seven
      methods.
AB  - Simple interval estimate methods for proportions exhibit poor coverage and can
      produce evidently inappropriate intervals. Criteria appropriate to the evaluation
      of various proposed methods include: closeness of the achieved coverage
      probability to its nominal value; whether intervals are located too close to or
      too distant from the middle of the scale; expected interval width; avoidance of
      aberrations such as limits outside [0,1] or zero width intervals; and ease of
      use, whether by tables, software or formulae. Seven methods for the single
      proportion are evaluated on 96,000 parameter space points. Intervals based on
      tail areas and the simpler score methods are recommended for use. In each case,
      methods are available that aim to align either the minimum or the mean coverage
      with the nominal 1 -alpha.

PMID- 9595617
TI  - Interval estimation for the difference between independent proportions:
      comparison of eleven methods.
AB  - Several existing unconditional methods for setting confidence intervals for the
      difference between binomial proportions are evaluated. Computationally simpler
      methods are prone to a variety of aberrations and poor coverage properties. The
      closely interrelated methods of Mee and Miettinen and Nurminen perform well but
      require a computer program. Two new approaches which also avoid aberrations are
      developed and evaluated. A tail area profile likelihood based method produces the
      best coverage properties, but is difficult to calculate for large denominators. A
      method combining Wilson score intervals for the two proportions to be compared
      also performs well, and is readily implemented irrespective of sample size.

PMID- 9595618
TI  - Equivalence test and confidence interval for the difference in proportions for
      the paired-sample design.
AB  - This paper considers a model for the difference of two proportions in a paired or
      matched design of clinical trials, case-control studies and also sensitivity
      comparison studies of two laboratory tests. This model includes a parameter
      indicating both interpatient variability of response probabilities and their
      correlation. Under the proposed model, we derive a one-sided test for equivalence
      based upon the efficient score. Equivalence is defined here as not more than 100
      delta per cent inferior. McNemar's test for significance is shown to be a special
      case of the proposed test. Further, a score-based confidence interval for the
      difference of two proportions is derived. One of the features of these methods is
      applicability to the 2 x 2 table with off-diagonal zero cells; all the McNemar
      type tests and confidence intervals published so far cannot apply to such data. A
      Monte Carlo simulation study shows that the proposed test has empirical
      significance levels closer to the nominal alpha-level than the other tests
      recently proposed and further that the proposed confidence interval has better
      empirical coverage probability than those of the four published methods.

PMID- 9595619
TI  - Development of a clinical prediction model for an ordinal outcome: the World
      Health Organization Multicentre Study of Clinical Signs and Etiological agents of
      Pneumonia, Sepsis and Meningitis in Young Infants. WHO/ARI Young Infant
      Multicentre Study Group.
AB  - This paper describes the methodologies used to develop a prediction model to
      assist health workers in developing countries in facing one of the most difficult
      health problems in all parts of the world: the presentation of an acutely ill
      young infant. Statistical approaches for developing the clinical prediction model
      faced at least two major difficulties. First, the number of predictor variables,
      especially clinical signs and symptoms, is very large, necessitating the use of
      data reduction techniques that are blinded to the outcome. Second, there is no
      uniquely accepted continuous outcome measure or final binary diagnostic
      criterion. For example, the diagnosis of neonatal sepsis is ill-defined. Clinical
      decision makers must identify infants likely to have positive cultures as well as
      to grade the severity of illness. In the WHO/ARI Young Infant Multicentre Study
      we have found an ordinal outcome scale made up of a mixture of laboratory and
      diagnostic markers to have several clinical advantages as well as to increase the
      power of tests for risk factors. Such a mixed ordinal scale does present
      statistical challenges because it may violate constant slope assumptions of
      ordinal regression models. In this paper we develop and validate an ordinal
      predictive model after choosing a data reduction technique. We show how
      ordinality of the outcome is checked against each predictor. We describe new but
      simple techniques for graphically examining residuals from ordinal logistic
      models to detect problems with variable transformations as well as to detect non
      proportional odds and other lack of fit. We examine an alternative type of
      ordinal logistic model, the continuation ratio model, to determine if it provides
      a better fit. We find that it does not but that this model is easily modified to
      allow the regression coefficients to vary with cut-offs of the response variable.
      Complex terms in this extended model are penalized to allow only as much
      complexity as the data will support. We approximate the extended continuation
      ratio model with a model with fewer terms to allow us to draw a nomogram for
      obtaining various predictions. The model is validated for calibration and
      discrimination using the bootstrap. We apply much of the modelling strategy
      described in Harrell, Lee and Mark (Statist. Med. 15, 361-387 (1998)) for
      survival analysis, adapting it to ordinal logistic regression and further
      emphasizing penalized maximum likelihood estimation and data reduction.

PMID- 9595620
TI  - Confidence limits based on the first occurrence of an event by V. T. George and
      R. C. Elston, Statistics in Medicine, 12, 685-690 (1993)

PMID- 9595622
TI  - Tests for equality of two correlated proportions by W. L. May and W. D. Johnson,
      Statistics in Medicine, 16, 1081-1096 (1997)

PMID- 9595621
TI  - Variation of sensitivity, specificity, likelihood ratios and predictive values
      with disease prevalence by H. Brenner and O. Gefeller, Statistics in Medicine,
      16, 981-991 (1997)

PMID- 9595623
TI  - Study of the protective immunity of co-expressed glycoprotein H and L of equine
      herpesvirus-1 in a murine intranasal infection model.
AB  - Equine herpesvirus-1 (EHV-1) glycoproteins H, and L (gH and gL) expressed
      individually or co-expressed by recombinant baculoviruses were used to immunise
      BALB/c mice prior to intranasal challenge in a murine model of respiratory
      infection. Only the co-expressed material (EHV-1 gH/gL) induced neutralising
      antibody (low levels). The same immunogen also produced the strongest cellular
      responses. Immunisation with gH/gL and, to a lesser extent, with gH alone was
      associated with a reduction of virus load in nasal turbinates and olfactory bulbs
      after challenge infection. Viraemia, detected by polymerase chain reaction, was
      also reduced. No such protective effects were observed for gL alone. Adoptive
      transfer of lymphocytes from gH/gL-immunised mice to naive mice subsequently
      challenged with EHV-1 indicated that both CD4+ and CD8+ cells had a role in
      protective immunity. Although clearance of EHV-1 from respiratory tissue was not
      as effective as previously found for glycoproteins D or C, these experiments
      provide evidence that the co-expression of EHV-1 gL with gH generates a
      conformational neutralising epitope which is not present in either molecule
      alone, and suggests that gH/gL antigen may have a better potential as a component
      of an EHV-1 vaccine than gH alone.

PMID- 9595624
TI  - Comparison of four tests to evaluate the reactivity of rabbit sera against
      envelope or Gag-related proteins of bovine leukemia virus (BLV).
AB  - Bovine leukemia virus (BLV) has a long latency period during which animals are
      inapparently infected, may spread the disease, and are only detected by
      serological techniques or by the most cumbersome molecular biology techniques. We
      have compared techniques for detecting either total antibodies (ELISA), anti-p24
      and Gag-related proteins (Western blot), or anti-gp51 (agar gel immunodiffusion,
      AGID, and syncytia inhibition, SI) in rabbits inoculated experimentally with
      inocula of variable immunogenicity. The two tests to detect antibodies to gp51
      correlated well in sera clearly positive or clearly negative by either one, but
      correlation was poor in the intermediate groups. All sera positive by AGID were
      also positive by ELISA, but results did not agree in sera negative by AGID, ELISA
      proving to be more sensitive. Western blot was a good technique for detecting
      antibodies against Gag-related proteins. However, no band was identified to
      clearly correspond to anti-Env-related proteins. As for other retroviruses,
      testing of animals for infection with BLV should include the detection of
      antibodies anti-Gag and anti-Env proteins.

PMID- 9595625
TI  - Experimental infection of cattle with several Borrelia burgdorferi sensu lato
      strains; immunological heterogeneity of strains as revealed in serological tests.
AB  - Twenty-three experimental cattle, mainly calves, were each inoculated 1-3 times
      with one of ten Finnish Borrelia burgdorferi sensu lato strains. All three
      genospecies were represented. Borreliae were administered mainly by both
      intravenous (about 10(6) to 10(9) spirochaetes) and intradermal (10(4)) routes,
      and on six occasions subcutaneously (10(3)) only. For infectivity control and
      comparison purposes mice and rabbits were inoculated simultaneously. Immune
      responses in cattle were monitored both with whole-cell sonicate enzyme-linked
      immunosorbent assay (IgG-ELISA) and indirect immunofluorescent assay (IgM-IgG
      IFA). Five Finnish strains and the American strain B31 were used as antigens. No
      clinical signs of borreliosis were observed. Of the strains, 7/10 were
      interpreted by the immune responses to have caused relatively short-term
      subclinical infections of varying intensity. Borreliae could not be isolated from
      blood or other organ specimens of cattle. A rough estimate of the mean infectious
      dose in the conditions of experiments is 10(6) to 10(7) organisms. In conclusion,
      the overall result appears to argue a low susceptibility of cattle to clinical
      borreliosis, at least when infected by Finnish strains of the agent. Significant
      antigen-specific differences were observed both by ELISA and IFA in detection and
      quantification of immune responses. As a rule, the homologous antigen was found
      to be the most sensitive. Genospecies differences were mostly distinct. Antigens
      of two Borrelia garinii isolates proved practically equal in sensitivity, whereas
      major differences were displayed between two Borrelia afzelii antigens. In an IFA
      study, an American (B31) and a Finnish B. burgdorferi sensu stricto strain proved
      equally sensitive as antigens. In two relatively strong primary immune responses
      the antigen-specific measurement differences were such that diagnostically in a
      cross-sectional study only the homologous antigen or an antigen of the same
      genospecies would have been sufficiently sensitive to show a positive result.

PMID- 9595626
TI  - Serological cross-reactivity between Brucella abortus and yersinia enterocolitica
      0:9: IV. Evaluation of the M- and C-epitope antibody response for the specific
      detection of B. abortus infections.
AB  - Smooth lipopolysaccharides (SLPS) from Brucella abortus contain A-epitopes
      against which the majority of serum antibodies are directed during infections.
      SLPS from Yersinia enterocolitica 0:9 possesses identical epitopes, which are the
      cause for serological cross-reactivity. All Brucella spp. possess M- and C
      epitopes which are not present in Y. enterocolitica 0:9. In order to examine the
      usefulness of these M- and C-epitopes for discriminatory serological testing, a
      panel of sera were used in this study, comprising sera from Y. enterocolitica 0:9
      infected heifers, sera from B. abortus-infected cattle of comparable strength in
      the serological brucellosis tests to the sera from Y. enterocolitica 0:9-infected
      heifers, sera from B. abortus-infected bovines with strong serological reactions
      and sera from animals free from B. abortus or Y. enterocolitica infections. These
      sera were tested in blocking ELISAs with seven M- and one C-epitope-specific
      monoclonal antibodies in combination with SLPS from B. melitensis M16 high in M
      epitopes as antigen. Strong B. abortus sera inhibited most strongly, while
      negative sera showed no or little inhibition. Sera with weak or intermediate
      titres blocked to a lower extent. Unexpectedly, the sera from Y. enterocolitica
      0:9-infected heifers showed inhibition behaviour virtually identical to the
      comparable sera from B. abortus infected animals. Absorbing out of the A-epitope
      specific serum antibodies with either Y. enterocolitica 0:9 SLPS or with Y.
      enterocolitica 0:9 bacteria, indicated the presence of M- or C-epitope-specific
      serum antibodies in some sera from B. abortus-infected cattle but not in the sera
      from Y. enterocolitica 0:9-infected animals. These results demonstrate that the M
      or C-epitope-specific antibody response in sera from B. abortus infected cattle
      is only of limited value for the serological discrimination between B. abortus
      and Y. enterocolitica 0:9 infections.

PMID- 9595627
TI  - Serological characterization and antimicrobial susceptibility of Streptococcus
      suis isolates from diagnostic samples in Denmark during 1995 and 1996.
AB  - At the Danish Veterinary Laboratory Streptococcus suis infections in pigs were
      diagnosed in 114 cases in 1995 and in 151 cases in 1996. Isolates were serotyped
      using specific antisera against type 1 through 28 and a total of 67 cases from
      1995 and 113 cases in 1996 were tested for resistance to 11 antimicrobial agents.
      The majority of cases were lung diseases (57%), followed by septicaemia (16%),
      meningitis (15%) and endocarditis (8%). Almost 96% of the isolates could be typed
      using the 28 antisera. The most common serotype was serotype 2 (29%), followed by
      serotype 7 (17%), and serotypes 3, 4 and 8 (9-10%). The remaining serotypes were
      observed in frequencies of less than 5%. Serotype 7 was more commonly isolated
      from septicaemia than the other serotypes. Serotype 2 was more commonly isolated
      from pigs older than 4 weeks compared to the other serotypes. Most isolates were
      susceptible to amoxycillin + clavulanate, ampicillin, ceftiofur, enrofloxacin,
      penicillin, spectinomycin, tiamulin and trimethoprim + sulphadiazine. A high
      frequency (> 30%) of resistance to tetracycline was observed. Among isolates of
      serotype 2, 9.7% were resistant to lincomycin and 12.9% to spiramycin. Among
      other serotypes 56.8% were resistant to lincomycin and spiramycin. The
      differences in susceptibility between isolates of serotype 2 and the other
      serotypes were statistically significant. Compared to a previous Danish study the
      distribution of serotypes of S. suis causing infections among pigs in Denmark has
      changed during the last 15 years.

PMID- 9595628
TI  - Characterization of a 54-kDa heat-shock-inducible protein of Pasteurella
      haemolytica.
AB  - Growth-condition-dependent antigens play a role in the virulence or protective
      capacity of many organisms. Enhanced production of an approximately 54-kDa
      protein was detected in heat-shocked cultures of Pasteurella haemolytica. The
      heat-shock-inducible protein cross-reacted with antibodies to 60-kDa heat-shock
      proteins of Mycobacterium tuberculosis, Chlamydia, and Escherichia coli GroEL. A
      probe containing the E. coli groEL operon hybridized with fragments of P.
      haemolytica chromosomal DNA on Southern blots. Immunoblots of the 54-kDa protein
      using serum from 20 calves that were challenged experimentally with P.
      haemolytica resulted in band densities that were significantly different between
      calves with high and low lesion scores. Results of the study suggest that the 54
      kDa heat-shock protein may be a growth-condition-dependent immunogen that is one
      component of resistance to pneumonic pasteurellosis.

PMID- 9595629
TI  - Sudden death in sheep associated with Clostridium sordellii.
AB  - Clostridium sordellii was isolated from 37 sheep, in 29 flocks, which died
      suddenly between 1993 and 1995. The sheep were of all ages, but the most severe
      gross lesions affected lambs four to 10 weeks of age. In older weaned lambs and
      ewes the gross changes were less marked and more variable. Thirty sheep suffering
      from a variety of other conditions were examined and C sordellii was not
      isolated. The isolation of C sordellii has been reported only twice before from
      sheep in Britain, and on both occasions no detailed investigations were
      described. The evidence from this study indicates that C sordellii should be
      considered when investigating the cause of sudden death in sheep of all ages in
      Britain.

PMID- 9595630
TI  - Detection of peste des petits ruminants virus antigen in conjunctival smears of
      goats by indirect immunofluorescence.
AB  - Peste des petits ruminants virus (PPRV) antigen was detected in conjunctival
      epithelial cells obtained from goats in the early or late stage of the disease by
      the use of a specific monoclonal antibody (mAb) to PPRV in an immunofluorescent
      antibody test (IFAT). The affected goats were sampled during an outbreak of peste
      des petits ruminants in Eritrea. Syncytia were also observed in some smears,
      consistent with a morbillivirus infection, but the IFAT was more sensitive than
      staining for syncytia in the detection of viral antigen, the two tests giving 63
      per cent and 40 per cent of animals, respectively, with positive tests. Positive
      immunofluorescence was observed in samples from goats in the early and late
      stages of the disease, but was not observed with a specific rinderpest mAb or
      with conjunctival smears from uninfected animals. It is concluded that
      preparation of conjunctival smears for staining for syncytia is a simple
      procedure which can be applied in the field, and by use of a specific mAb PPRV
      infection can be rapidly confirmed and differentiated from rinderpest.

PMID- 9595631
TI  - Ultrasonographic appearance of normal superficial cervical and subiliac lymph
      nodes in cattle.
AB  - The superficial cervical and the subiliac lymph nodes of 18 healthy, non-pregnant
      Simmental cows with a mean (sd) age of 5-6 (1.6) years were examined
      ultrasonographically in transverse and longitudinal planes with a real-time B
      mode unit equipped with a 7.5 MHz linear-transducer. The position, demarcation
      and echogenicity of the lymph nodes were examined, and the craniocaudal and
      lateromedial diameters of each lymph node were measured three times within a
      period of six weeks. The pole to pole length of the lymph nodes was determined
      with a tape measure on the surface of the skin because the whole length could not
      be imaged in a single scan field. The gross anatomical and histological results
      showed that the lymph nodes were normal. Ultrasonographically, they were well
      demarcated from the adjoining muscular and subcutaneous tissue. Their internal
      structure was characterised by an anechoic to hypoechoic cortical zone
      corresponding to the lymphoid tissue, and an echogenic medullary zone, where the
      lymphatic sinuses converge towards the hilus and produce numerous acoustic
      interfaces. In all the lymph nodes, the hilar area had an echoic to hyperechoic
      appearance. The mean (sd) pole to pole length of the superficial cervical lymph
      nodes was 15.5 (3.2) cm and of the subiliac lymph nodes 13.5 (2.4) cm. The mean
      craniocaudal and lateromedial diameters of the superficial cervical lymph nodes
      were 2.8 (0.3) cm and 1.6 (0.3) cm, and those of the subiliac lymph nodes were
      2.4 (0.4) cm and 1.1 (0.3) cm. The ultrasonographic morphology of these normal
      lymph nodes was consistent and provides basic reference data for the
      investigation of lymphadenopathies in cattle.

PMID- 9595632
TI  - Efficacy of intranasal administration of formalin-killed Pasteurella haemolytica
      A2 against intratracheal challenge in goats.
AB  - A trial was conducted to compare the efficacy of intranasal vaccination in
      protecting goats against pneumonic pasteurellosis with intramuscular vaccination
      using an oil adjuvant vaccine, and a combination of the two methods. Forty goats
      were divided into four equal groups. Group 1 was vaccinated twice intranasally
      with formalin-killed Pasteurella haemolytica A2, group 2 was vaccinated twice
      intramuscularly with an oil adjuvant vaccine containing P haemolytica A7, and
      group 3 was initially vaccinated intranasally with the formalin-killed P
      haemolytica A2 followed by intramuscular vaccination with the oil adjuvant
      vaccine. In each group the two vaccinations were carried out four weeks apart.
      Group 4 was the unvaccinated control group. All goats were challenged
      intratracheally with 4 ml of an inoculum containing live P haemolytica A2 at a
      concentration of 1.3 x 10(7) colony forming units/ml two weeks after the last
      vaccination and were killed 14 days after the challenge. Although group 2 showed
      the highest clinical score following the challenge, deaths were observed only in
      group 3. Three goats in group 1 had pneumonic lung lesions, compared with six
      goats in group 2 and all the goats in groups 3 and 4. The lung lesions in group 1
      were significantly (P < 0.05) less severe than in groups 3 and 4. Similarly, the
      lesions in group 2 were markedly less severe than in groups 3 and 4, although the
      differences were not significant. The difference between the extent of the lung
      lesions in the goats in groups 1 and 2 was not significant. Antibody against P
      haemolytica A2 in group 1 reached peak levels and was significantly (P < 0.01)
      higher than in the control group one week after the second vaccination, before
      declining.

PMID- 9595633
TI  - Concordance with reference sera of a recombinant protein ELISA for maedi-visna
      antibody detection.

PMID- 9595634
TI  - Concurrent paratuberculosis and parasitism in a five-month-old lamb in The
      Netherlands.

PMID- 9595635
TI  - Acute disseminated candidiasis in a puppy associated with parvoviral infection.

PMID- 9595636
TI  - Total pectoral ectopia cordis and other congenital malformations in a calf.

PMID- 9595637
TI  - Staffing at veterinary schools.

PMID- 9595638
TI  - Withdrawal period for benzathine penicillin preparations.

PMID- 9595639
TI  - Review of counselling in a transfusion service: the London (UK) experience.
AB  - Donor (and recipient) counselling within the Transfusion Service in the UK has
      grown in volume and complexity over the last 10 years. The addition of new tests
      for donated blood and the growth of bone marrow transplantation have increased
      the demands on counselling staff. New initiatives, such as the HCV look-back
      programme, have required an extension of the skills and knowledge of staff
      involved in counselling.

PMID- 9595640
TI  - How some attitudes, beliefs and motivations of Spanish blood donors evolve over
      time.
AB  - OBJECTIVES: To determine whether the attitudes, beliefs and motivations of blood
      donors evolve over time. MATERIALS AND METHODS: Using questionnaires a 7-year
      longitudinal study of a cohort of 126 donors was performed to gather their
      sociodemographic characteristics and their attitudes, beliefs and motivations
      relating to blood donation. RESULTS: Changes were observed in a large number of
      beliefs and attitudes, with a reduction in fear about donation and in the need
      for rewards and recognition, and an increase in comfort during donation and in
      attitudes of duty and solidarity. However, the motivations of 65% of the sample
      did not change. CONCLUSION: With the passage of time, donors' attitudes and
      beliefs evolve in a way that is favourable to blood donation and their
      motivations remain stable.

PMID- 9595641
TI  - Application of the human hepatitis B virus core antigen from transgenic tobacco
      plants for serological diagnosis.
AB  - BACKGROUND AND OBJECTIVES: The aim was to produce HBcAg from plants more cheaply
      than can be done by other currently available means, and to apply such antigen to
      immunoassay procedures for pretransfusion testing of donor blood. MATERIALS AND
      METHODS: Transgenic Nicotiana tabacum cv. SR-1 plants expressing the human
      hepatitis B virus (HBV) core antigen (HBcAg) gene were generated by Agrobacterium
      mediated transformation. The recombinant product, called tHBcAg, can assemble
      itself into a spherical particle with a diameter of 25 to 30 nm, and can maintain
      two antigenic determinants of HBcAg, namely HBc/alpha and HBc/beta. Partly
      purified tHBcAg was used in the hemagglutination-inhibition (HI) test, as
      routinely used by the Japanese Blood Center, to test a panel of 524 blood units
      taken from HBV-positive donors. RESULTS: In the HI test, tHBcAg showed serologic
      properties comparable to that from Escherichia coli, the standard antigen used in
      the Japanese Blood Center. CONCLUSIONS: Transgenic plants can produce reagents
      for serologic testing and perhaps even such medical materials as oral vaccines.

PMID- 9595642
TI  - Solid-phase immunoassays for HCV antibodies in Gamimune N.
AB  - BACKGROUND AND OBJECTIVES: Occasional false-positive results for the presence of
      HCV antibodies occur when testing pH 4 Gamimune N immune globulin intravenous
      (human) (IGIV) using commercially available immunoassay kits. We investigated the
      causes. MATERIALS AND METHODS: EIA test results were compared with Nile red
      hydrophobic dye binding. RESULTS: There was a strict correlation of reactive EIA
      results with a larger relative proportion of molecules in a low pH-dependent
      hydrophobic conformation. Conversely, the greater the hydrophilic contribution to
      the population of IgG molecules (favored at neutral pH), the more nonreactive the
      EIA test results became for the same lots. An IGIV test preparation procedure
      consisting of pH neutralization followed by 48-hour incubation at 37 degrees C
      decreased positive test result outcomes in four different immunoassay formats by
      shifting the IgG population to a more hydrophilic conformation. CONCLUSIONS: The
      hydrophobic conformation of IgG favored at low pH appears to give rise to
      significant levels of nonspecific binding in solid phase immunoassays.

PMID- 9595643
TI  - Epidemiological and clinical aspects of hepatitis G virus infection in blood
      donors and immunocompromised recipients of HGV-contaminated blood.
AB  - BACKGROUND AND OBJECTIVES: The infectiousness and clinical relevance of the newly
      discovered blood-borne Flaviviridae-like agent, termed hepatitis G virus (HGV),
      are not well understood. MATERIALS AND METHODS: Twenty-three transfusion
      recipients of two HGV-affected long-term blood donors were studied for HGV genome
      and antibodies to the putative envelope 2 glycoprotein (anti-E2) of HGV. Nine
      recipients had nonhematological disorders and 14 suffered from severe
      hematological diseases and 7 of them received allogeneic bone marrow or blood
      stem cell transplantation. The molecular epidemiology of the observed HGV
      infection was studied by direct sequencing of parts of the 5'-noncoding region,
      NS3, and NS5 region of HGV in the 2 long-term donors and in their 6 recipients
      who became HGV RNA positive. Additionally, 549 individuals-homologous (n = 254)
      and autologous blood donors (n = 202), and medical staff (n = 89)--were
      investigated for the presence of HGV RNA. RESULTS: HGV RNA in serum was found in
      15 of the 23 (65%) transfusion recipients with known exposure of HGV-contaminated
      blood. Seven of the remaining 8 recipients showed only an anti-E2 response,
      indicating previous HGV infection with spontaneous clearance of the virus. In one
      recipient neither HGV RNA nor anti-E2 could be detected. Molecular evidence for
      HGV transmission by the 2 donors was found in 3 of the 6 recipients studied. The
      alanine aminotransferase levels were not significantly different in the HGV RNA
      positive and negative recipients, and none of the 23 recipients developed
      posttransfusion hepatitis. Persistent HGV infection was observed especially in
      recipients with severe hematological disorders or in those in whom intensive
      immunosuppressive treatment was necessary. Of the 549 individuals studied, 10
      (1.8%) were healthy carriers of HGV RNA. CONCLUSION: The persistence of
      transfusion-acquired HGV infection is not associated with acute or chronic
      hepatitis, but may be influenced by the recipient's underlying disease.

PMID- 9595644
TI  - Improved blood preservation with 0.5CPD erythro-sol. Coagulation factor VIII
      activity and erythrocyte quality after delayed separation of blood.
AB  - BACKGROUND AND OBJECTIVES: Delay between blood collection and the separation of
      its components may result in lowered yield of factor VIII (FVIII) and loss of 2,3
      biphosphoglycerate (2,3-BPG). This study was to see whether the use of 0.5 CPD
      resulted in better preservation of FVIII and maintenance of 2,3-BPG. MATERIALS
      AND METHODS: 55 units of blood were collected in 0.5CPD and 48 in CPD SAG-M. Ten
      of the collections were paired, so that the same donors were bled in a single
      session partly in an 0.5CPD system and partly in CPD SAG-M. After collection, the
      blood was promptly cooled to 20 degrees C and stored at that temperature for up
      to 24 h. RESULTS: Preservation of FVIII activity was significantly better in
      0.5CPD compared with CPD. The content of von Willebrand factor was stable in the
      anticoagulant solutions for 24 h at that temperature. Plasma separated from both
      media had how levels of prothrombin fragment 1 + 2 and complement activation.
      Paired collections substantiated previous reports that red cell storage is
      significantly improved in 0.5CPD compared with CPD SAG-M with respect to 2,3-BPG
      and haemolysis. CONCLUSIONS: Red cell metabolism and oxygen-releasing capacity
      are kept at acceptable levels in 0.5CPD blood for 24 h at 20 degrees C before
      component separation. The concentration of red cell 2,3-BPG remained at normal or
      slightly subnormal levels during further storage in 0.5CPD at 4 degrees C for 2-4
      weeks before gradual decay to an average of 39% at 48 days.

PMID- 9595645
TI  - Immunomodulating effect of blood transfusion: is storage time important?
AB  - OBJECTIVES: TNF-alpha and IL-2 are important cytokines in macrophage and T
      lymphocyte activity against infection and dissemination of malignant cells. We
      studied the influence of supernatants from stored whole blood and buffy-coat
      depleted SAGM (saline, adenine, glucose and mannitol) blood in stimulating TNF
      alpha and IL-2 release in an ex vivo assay. METHODS: Supernatants of 10 units of
      whole blood and 10 units of SAGM blood were collected after 1, 21 and 35 days of
      standard blood bank storage. Heparinized blood from 20 healthy volunteers (as
      'recipients'), corresponding in ABO and Rh type to the stored blood, were used in
      a culture system with LPS and PHA as stimulators of TNF-alpha and IL-2 release.
      The effect of added supernatants, from either stored whole blood or SAGM blood,
      on cytokine release was evaluated compared to saline as control. TNF-alpha
      concentration was analyzed by ELISA after culture for 24 h and IL-2 after 72 h,
      respectively. RESULTS: Supernatants from both stored whole blood and SAGM blood
      showed a significant decrease in both LPS- and PHA-stimulated TNF-alpha release
      that was dependent on storage time. IL-2 was not detected in response to LPS
      stimulation. PHA-stimulated IL-2 release was significantly reduced and related to
      storage time of both whole blood and SAGM blood. CONCLUSIONS: Recipient cytokine
      release induced by blood transfusion seems to be dependent on storage time. This
      may have implications in transfusion-induced immune modulation.

PMID- 9595646
TI  - Quality and safety of platelet apheresis concentrates produced with a new
      leukocyte reduction system.
AB  - OBJECTIVES: Contaminating white blood cells (WBC) in apheresis platelet
      concentrates (PC) can cause a variety of adverse effects after platelet
      transfusion. To obtain PCs with low WBC contamination, a new leukoreduction
      system (LRS) utilizing 'fluidized particle bed' technology has recently been
      introduced. METHODS: We prospectively examined the effect of LRS apheresis on the
      donor, the quality of the resulting PCs (n = 120), and the platelet increment in
      the corresponding recipients. Conventionally prepared apheresis PCs served as
      control group (n = 27). Platelet glycoproteins were examined by flow cytometry.
      RESULTS: In LRS apheresis, we observed no serious adverse effects on the donors,
      but the postdonation absolute lymphocyte counts were reduced from 1,787 +/-
      505/microliter to 1,405 +/- 383/microliter (p < 0.001). Comparable results were
      seen in non-LRS donors. The collection efficiency of the LRS procedures was 50.0
      +/- 7.6%, resulting in a yield of 4.3 +/- 1.0 x 10(11) platelets/PC. In flow
      cytometry, platelet glycoproteins in LRS PCs were not elevated: mean fluorescence
      of CD62 (6 +/- 4) or CD63 (9 +/- 3) in comparison with non-LRS PCs (mean
      fluorescence of CD62: 7 +/- 4, CD63: 8 +/- 3). Median leukocyte contamination of
      the LRS PCs was 0.41 x 10(5) (range 0.07-8.5) WBCs/unit. In 43 recipients, the 24
      hour corrected count increments after transfusion of LRS PCs (12,530 +/- 8,761)
      were essentially the same as those of 20 recipients of non-LRS PCs (13,133 +/-
      9,812; p = 0.75). CONCLUSIONS: LRS apheresis appears to be a safe procedure,
      which produced effective PCs with few contaminating leukocytes. With new
      apheresis technology, filtration of PCs may become superfluous.

PMID- 9595647
TI  - Evaluation of a platelet apheresis technique for the preparation of leukocyte
      reduced platelet concentrates.
AB  - OBJECTIVES: Reduction of the white blood cell (WBC) contamination in platelet
      concentrates (PC) protects patients from the immunological and infectious side
      effects of platelet transfusion caused by WBC. This can be done either by
      filtration of the PC or by improved apheresis techniques that yield WBC-poor
      preparations. METHODS: To evaluate an improved technique for platelet collection,
      we carried out 201 separations in 89 healthy cytapheresis donors using the new
      COBE Spectra leukoreduction system (LRS) and compared the results with those of
      standard dual-needle separations obtained with the same cell separator. RESULTS:
      A small but statistically significant difference was found in platelet collection
      efficiency in comparison with the standard non-LRS software procedures (LRS: 52.6
      vs. 56.3% for the reference). However, median WBC contamination was only 0.01 x
      10(6) WBC per LRS product. This significant (p < 0.0005) improvement corresponds
      to a 10-fold reduction of WBC as compared with the standard dual-needle
      technique. CONCLUSIONS: The COBE Spectra LRS system produced PCs with a platelet
      collection efficiency nearly equal to previous techniques and with a residual WBC
      content satisfying even the most stringent criteria for WBC-depleted blood
      components. As this purity is achieved without important platelet loss,
      conventional fiber filtration no longer seems necessary in this kind of PC.

PMID- 9595648
TI  - Histamine synthesis by white cells during storage of platelet concentrates.
AB  - OBJECTIVES: To resolve the question whether histamine, like some cytokines, is
      actively synthesized during storage of platelet concentrates. METHODS: We
      prepared conventional buffy coat platelet concentrates and stored them in the
      usual way at 22 degrees C. Disodium cromoglycate was added to one series, saline
      to the controls. Samples were taken at intervals, to be tested for histamine and
      interleukin-6 (IL-6). RESULTS: The plasma histamine level increased from a median
      of 1.02 ng/ml (range 0.11-3.27) to 12.9 ng/ml (range 4.30-32.9) whereas the total
      histamine content of the platelet concentrates remained unchanged during the 5
      day storage period. In contrast, the total content of IL-6 increased rapidly.
      CONCLUSION: Histamine is not synthesized during storage of platelets, whereas IL
      6 is. The addition of disodium cromoglycate, a substance that inhibits
      granulocyte activation, had no effect on the release of histamine or on the total
      histamine content at various storage times.

PMID- 9595649
TI  - Alternative therapies for neonatal autoimmune thrombocytopenia.
AB  - OBJECTIVE: This study was performed to test whether corticosteroids were superior
      to intravenous immunoglobulins (IVIG) in the treatment of neonatal autoimmune
      thrombocytopenia (NAT). METHODS: All cases received IVIG, and unresponsive cases
      received corticosteroids. RESULTS: Of 7 babies who received IVIG, only 1
      responded. The 6 remaining cases received corticosteroids thereafter, and all of
      them responded well to this therapy. CONCLUSIONS: Corticosteroids may be more
      effective than IVIG in NAT.

PMID- 9595650
TI  - Severe neonatal alloimmune thrombocytopenia due to anti-HPA-3a.
AB  - BACKGROUND AND OBJECTIVES: Neonatal alloimmune thrombocytopenia is usually
      attributable to HPA-la antibodies. We report a case of parental platelet antigen
      incompatibility associated with a severe neonatal thrombocytopenia secondary to
      alloimmunization to HPA-3a. MATERIALS AND METHODS: Platelet antibodies were
      detected by the monoclonal antibody-specific immobilization of platelet antigens,
      genotyping of the platelets by PCR, and HLA typing by serologic procedures and
      PCR. RESULTS: Genotyping of maternal and paternal platelets confirmed the
      incompatibility in the HPA-3a system. It is noteworthy that the mother is of the
      HLA type DRB3*0101, is ABO-incompatible with her husband, and also has HLA class
      I antibodies. CONCLUSION: Severe neonatal thrombocytopenia associated with HPA-3a
      alloimmunization is infrequent and all the factors mentioned above could have
      played a role in the severity of the disease.

PMID- 9595651
TI  - Outcome of transfusion of K:11 erythrocytes in a patient with anti-K11 antibody.
AB  - BACKGROUND AND OBJECTIVES: The clinical significance of anti-K11 in red cell
      transfusion therapy is unknown. We report the outcome of transfusion of K:11
      erythrocytes into a patient with a known anti-K11 antibody. MATERIALS AND
      METHODS: The patient was monitored clinically following transfusion of 11 units
      of K:11 erythrocytes. A red cell survival study with K:11 erythrocytes and a
      monocyte monolayer assay (MMA) were performed. RESULTS: No adverse clinical
      outcome was detected. The red cell survival study showed normal survival of K:11
      erythrocytes, and the MMA showed no increase in reactive monocytes. CONCLUSION:
      These findings suggest that K:11 red cells can safely be transfused to
      individuals with anti-K11 antibody.

PMID- 9595652
TI  - Anti-HBc in blood donors.

PMID- 9595653
TI  - Leucocytes can be eliminated from plasma by filtration prior to viral
      inactivation with methylene blue.

PMID- 9595654
TI  - Low-cost screening of blood for HCV infection in the developing world.

PMID- 9595655
TI  - Routine screening of blood donations for HCV RNA.

PMID- 9595656
TI  - High prevalence of HGV/GBV-C infection in polytransfused patients with
      thalassemia major.

PMID- 9595657
TI  - Integrative vector for stable transformation and expression of a beta-1,3
      glucanase gene in Clavibacter xyli subsp. cynodontis.
AB  - Clavibacter xyli subsp. cynodontis is an endophytic Gram-positive bacterium that
      is able to colonize the xylem tissue of various plants. We constructed an
      integrative vector that can carry foreign genes into a repetitive chromosomal
      element of C. xyli subsp. cynodontis. Using this vector, we transformed C. xyli
      subsp. cynodontis with a gene coding for an endoglucanase enzyme under the
      control of a strong promoter that was previously isolated from the genome of C.
      xyli subsp. cynodontis. The transformed bacteria efficiently expressed active
      glucanase and secreted it into the culture medium. The vector has the advantage
      of being stably maintained in the chromosome; the transformations were maintained
      without antibiotic selection both in in vitro culture and in bacteria growing in
      maize xylem.

PMID- 9595658
TI  - Disassociation of sigma subunit from RNA polymerase of Xanthomonas oryzae pv.
      oryzae by phage Xp10 infection.
AB  - The sigma subunit of Xanthomonas oryzae pv. oryzae is disassociated from host RNA
      polymerase after phage Xp10 infection. To clarify the possible mechanism for this
      observation, sigma subunit was purified and an antiserum against sigma subunit
      was prepared. Immunoprecipitation of RNA polymerase by the anti-core RNA
      polymerase antiserum, followed by immunoblotting with anti-sigma subunit
      antibody, revealed that sigma subunit was lost from RNA polymerase within 10
      minutes after Xp10 infection. Loss of sigma subunit was not observed under other
      stress conditions including heat and cold stress, starvation and growth to
      stationary phase. Two-dimensional immunoblotting analysis did not reveal any
      covalent modification of either sigma subunit or RNA polymerase after Xp10
      infection. These results suggest that separation of th subunit from RNA
      polymerase may be due to competition with other binding factors.

PMID- 9595659
TI  - Differential temperature modulation by H-NS of the fimB and fimE recombinase
      genes which control the orientation of the type 1 fimbrial phase switch.
AB  - Phase variation of type 1 fimbriation in Escherichia coli is associated with the
      inversion of a 314-bp DNA element. This DNA switch directs transcription of fimA,
      encoding the major type 1 fimbrial subunit, in the on orientation but not in the
      off orientation. Inversion of the DNA element requires either FimB (confers both
      on and off orientations) or FimE (confers off orientation). Here we show, by
      chromosomally located fimB- and fimE-lacZ cassettes in isogenic strain sets
      differing only in the hns locus, how the global regulator H-NS affects the
      expression of type 1 fimbriae. H-NS was found to downregulate fimB and fimE in a
      temperature-dependent manner which affected the genes inversely at 30 degrees C
      and 37 degrees C. By gel-retardation assays H-NS binding was demonstrated to the
      regions containing the fimB promoter and the fimE promoter, respectively. In
      vitro recombination analysis suggested no direct involvement of H-NS in the
      inversion of the phase switch. Rather than directly affecting the switching
      process per se, it appeared that the orientation of this element was affected by
      the differential temperature modulation of H-NS of the fimB and fimE genes. Taken
      together the results suggest that H-NS modulates expression of type 1 fimbriae in
      a way which seems to favor a fimbriate state at the mammalian body temperature.

PMID- 9595660
TI  - Identification of a human cDNA clone that mediates adherence of pathogenic
      Neisseria to non-binding cells.
AB  - Neisseria gonorrhoeae and Neisseria meningitidis are exclusively human pathogens.
      A crucial property of the pathogenicity of neisserial infection is the ability to
      adhere to human epithelial cells. Pili mediate adherence of these bacteria to
      target cells and thereby promote colonization and infection of mucosal surfaces.
      In order to identify and to learn more about the initial event during infection,
      a cDNA clone from a human cervical epithelial cell line was identified in a
      panning experiment using purified gonococcal pili as probe. Upon transfection of
      the cloned cDNA into COS-7 cells, both gonococci and meningococci adhered to
      these otherwise non-binding cells. The deduced amino acid sequence of the cDNA
      clone showed homology to a recently reported human cDNA, called WWP2, that
      encodes an N-terminal C2-like domain. The C2 domain has been shown to bind
      membrane phospholipids in a calcium-dependent manner and is thought to function
      in the intracellular compartmentalization of proteins. Antiserum raised against
      the product encoded by the cDNA did not inhibit bacterial adherence, indicating
      that the cloned gene is most likely involved in up-regulation of a surface
      receptor for pathogenic Neisseria.

PMID- 9595661
TI  - Involvement of the RpoN protein in the transcription of the oprE gene in
      Pseudomonas aeruginosa.
AB  - OprE is a channel-forming outer membrane protein of Pseudomonas aeruginosa, the
      expression of which is induced under anaerobic conditions. We constructed various
      mutants and observed the effects on oprE expression. Deficiency in RpoN, an
      alternative sigma factor for RNA polymerase, abolished oprE expression under
      aerobic conditions, but did not affect the expression under anaerobic conditions.
      One mutation on the putative RpoN recognition site also caused reduction of oprE
      expression. The region 500 nucleotides upstream of the mRNA start site was
      required for optimal oprE transcription, which contains an AT-rich region
      including a putative integration host factor binding site. These results indicate
      that OprE production is directly or indirectly controlled by RpoN but also
      require some other regulatory proteins bound to the upstream region.

PMID- 9595662
TI  - Transfer of plasmid pTO1 from Escherichia coli to various representatives of the
      order Actinomycetales by intergeneric conjugation.
AB  - Plasmid pTO1 containing the oriT fragment from RK2, the Escherichia coli
      replication function from pBR322, and a DNA fragment of actinophage phi C31 with
      the attachment site was transferred from E. coli S17-1 to strains of the genera
      Actinomadura, Arthrobacter, Micromonospora, Nocardia, Rhodococcus, and to 16
      strains of the genus Streptomyces. The frequency of conjugant formation was 1 x
      10(-3)-1 x 10(-5) depending on the strain. Hybridization experiments demonstrated
      that plasmid pTO1 integrates into chromosomes of a number of the recipient
      strains examined.

PMID- 9595663
TI  - The phylogenetic relationships of Chlorobium tepidum and Chloroflexus aurantiacus
      based upon their RecA sequences.
AB  - Using RecA as the phylogenetic marker, the relationships of the green sulfur
      bacterium Chlorobium tepidum and the green non-sulfur bacterium Chloroflexus
      aurantiacus to other eubacteria were investigated. The recA genes of the two
      organisms were cloned, and the resulting protein sequences aligned with 86 other
      eubacterial RecA sequences. Cb. tepidum was placed as the nearest relative to the
      Cytophaga/Flexibacter/Bacteriodes group, a relationship supported by results
      obtained with several phylogenetic markers. Cf. aurantiacus was placed near
      Chlamydia trachomatis and the high-GC Gram-positives; however, this branching
      pattern was not strongly supported statistically by bootstrap analyses. Possible
      reasons for this ambiguity are discussed.

PMID- 9595664
TI  - Nitrous oxide reductase (nosZ) gene-specific PCR primers for detection of
      denitrifiers and three nosZ genes from marine sediments.
AB  - Two PCR primer sets for the nitrous oxide reductase gene (nosZ) were developed.
      The initial primers were based on three sequences in GenBank and used to amplify
      nosZ from continental shelf sediments and from two denitrifiers in culture,
      Thiosphaera pantotropha and Pseudomonas denitrificans. Three unique marine
      sediment nosZ genes were identified and sequenced. The marine nosZ genes were
      most closely related to the nosZ genes of Paracoccus denitrificans or to
      Rhizobium meliloti. Alignment of all nosZ sequences currently available (n = 10)
      facilitated redesign of the PCR primers. Three new primer sets which amplify 1100
      bp, 900 bp and 250 bp regions of the nosZ gene were designed and tested. The new
      primers robustly amplified nosZ fragments from samples in which the initial nosZ
      primers were only marginally successful.

PMID- 9595665
TI  - The detection of insertion sequences within the human pathogen Burkholderia
      pseudomallei which have been identified previously in Burkholderia cepacia.
AB  - Using primers designed from the nucleotide sequences of five insertion elements
      identified previously in Burkholderia cepacia, the presence of two insertion
      sequences (IS406 and IS407) was detected in chromosomal DNA isolated from strains
      of the human pathogen Burkholderia pseudomallei. The IS407 homologue was cloned
      from B. pseudomallei NCTC 4845 and nucleotide sequenced to confirm its identity
      and degree of homology with B. cepacia IS407. A PCR amplification product from B.
      pseudomallei NCTC 4845 DNA provided an IS407 probe which was used to determine,
      by Southern blotting, the number and location of copies of IS407 in ten strains
      of B. pseudomallei and four representatives from three of the five genomovars of
      B. cepacia.

PMID- 9595666
TI  - Naturally occurring isolates of Neisseria gonorrhoeae, which display anomalous
      serovar properties, express PIA/PIB hybrid porins, deletions in PIB or novel PIA
      molecules.
AB  - The por gene of Neisseria gonorrhoeae encodes the Protein I porin responsible for
      serovar specificity. In this study the por genes have been sequenced from
      clinical isolates which exhibited anomalous serovar reactivity. One group of
      'intermediate' strains differed significantly from both Protein IA and IB
      strains, were more closely related to IA but appeared to represent a distinct
      class of Protein I. Another strain was closely related to Protein IB of serovar
      IB-6 but contained a deletion of six amino acids in surface exposed loop 6 which
      removed epitopes recognized by IB specific monoclonal antibodies. The third group
      of strains, which reacted with both IA and IB specific monoclonal antibodies,
      expressed hybrid Protein I molecules containing both IA and IB epitopes. These
      strains appeared to originate from a double crossover between Proteins IA and IB
      with the amino and carboxy terminal residues homologous to IB while the surface
      exposed loop 6 demonstrated close homology to IA. This is the first demonstration
      of naturally occurring gonococci expressing a hybrid Protein IA/IB.

PMID- 9595667
TI  - Ca(2+)-ATPases of Saccharomyces cerevisiae: diversity and possible role in
      protein sorting.
AB  - The PMR1 gene of Saccharomyces cerevisiae is thought to encode a putative Ca(2+)
      ATPase [1]. Membranes isolated from wild-type cells and from pmr1 null mutant of
      S. cerevisiae were fractionated on sucrose density gradients. In the pmr1 mutant
      we found a decrease in activity of the P-type ATPase and of ATP-dependent,
      protonophore-insensitive Ca2+ transport in light membranes, that comigrate with
      the Golgi marker GDPase. We conclude that the product of the PMR1 gene (Pmr1p) is
      indeed a Ca(2+)-ATPase of the Golgi and Golgi-like membranes. Surprisingly, the
      pmr1 null mutation abolished Ca(2+)-ATPase activity in Golgi and/or Golgi-like
      membranes only to 50% under conditions where they are separated from vacuolar
      membranes. This indicates that an additional Ca(2+)-ATPase is localized in Golgi
      and/or Golgi-like membranes. Moreover, a third Ca(2+)-ATPase is found in the ER
      and ER-like membranes. The data are consistent with the assumption that these
      Ca(2+)-ATPases are encoded by gene(s) different from PMR1. Disruption of PMR1
      Ca(2+)-ATPase causes significant redistribution of enzyme activities and of total
      protein in compartments of the secretory pathway. A decrease in activity is
      observed for three integral membrane proteins: NADPH cytochrome c reductase,
      dolichyl phosphate mannose synthase, and Ca(2+)-ATPase, and also for total
      protein in Golgi, Golgi-like compartments and in vacuoles, whereas a
      corresponding increase of these activities is observed in endoplasmic reticulum
      and endoplasmic reticulum-like membranes. We assume that Ca(2+)-ATPases and
      sufficient Ca2+ gradients across the organellar membranes are important for the
      correct sorting of proteins to the various compartments of the secretory
      apparatus.

PMID- 9595668
TI  - The Bacillus subtilis glpD leader and antiterminator protein GlpP provide a
      target for glucose repression in Escherichia coli.
AB  - Expression of the Bacillus subtilis glpD gene which encodes glycerol-3-phosphate
      (G3P) dehydrogenase is regulated by the GlpP protein which, in the presence of
      G3P, causes antitermination of transcription of glpD. The glpD gene leader fused
      to lacZ was integrated into the chromosome of Escherichia coli deleted for the
      lac operon and carrying the B. subtilis glpP gene on a plasmid. beta
      Galactosidase activity of this strain was increased by the addition of G3P. When
      G3P and glucose, glucose-6-phosphate or fructose-6-phosphate were added, beta
      galactosidase activity was reduced showing that GlpP mediates catabolite
      repression of transcription from the glpD leader in the absence of any other B.
      subtilis protein.

PMID- 9595669
TI  - Cloning and characterization of the gene encoding the primary sigma-factor of
      Campylobacter jejuni.
AB  - The rpoD gene encoding the primary sigma-factor of Campylobacter jejuni was
      amplified from genomic DNA with degenerate oligonucleotide primers. The complete
      gene encodes a polypeptide of 622 amino acids and has a deduced M(r) of 72.6 kDa.
      This polypeptide is 40% identical to the RpoD (sigma 70) protein of Escherichia
      coli and has 66% identity with the Helicobacter pylori RpoD protein. A C. jejuni
      sigma 70 promoter, not recognized by the E. coli sigma 70 factor, could be
      activated in this bacterium in the presence of the cloned C. jejuni RpoD protein.

PMID- 9595670
TI  - A PCR fingerprinting technique to distinguish isolates of Lactococcus lactis.
AB  - A fingerprinting technique similar to repetitive extragenic palindromic PCR was
      developed to identify strains of Lactococcus lactis. The method distinguishes
      closely related strains and discriminates among some with identical ldh
      sequences. The fingerprinting primer LL-Rep1 complements a moderately repeated
      sequence found in low G + C Gram-positive bacteria and may therefore prove useful
      for discriminating among strains of other low G + C Gram-positive species.

PMID- 9595671
TI  - Physiological consequences of the over-production of E. coli truncated molecular
      chaperone DnaJ.
AB  - In Escherichia coli one of the main molecular chaperones is DnaJ (hsp40) which
      mediates in a variety of highly conserved cellular process including protein
      folding reactions and assembly/disassembly of protein complexes. In this study we
      have investigated the toxicity of the over-production of DnaJ and two truncated
      polypeptides by examining growth rates, cell morphology and cell viability. Full
      length DnaJ (1-375 amino acids) and truncated polypeptides, corresponding to the
      last 176 (containing the substrate binding domain) and 266 (containing the zinc
      finger-like domain) amino acids of the C-terminus of DnaJ, DnaJ delta 1-199 and
      delta 1-108 respectively, were over-produced via IPTG induction. High levels of
      synthesis were determined by SDS-PAGE and Western blotting using anti-DnaJ
      antibodies. The over-production of full-length DnaJ resulted in a low degree of
      filamentation and a decrease in cell viability. However, over-production of DnaJ
      truncated polypeptides, especially DnaJ delta 1-108, was bactericidal and
      resulted in a loss of viability and defective septation.

PMID- 9595672
TI  - Constitutive choline transport in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa has a choline uptake system which is expressed in bacteria
      grown in the presence of succinate and ammonium chloride as the carbon and
      nitrogen source, respectively. This system obeys Michaelis-Menten kinetics with
      an apparent Km value of 53 microM; its activity is not inhibited by high
      osmolarities in the medium but is partially inhibited by choline metabolites such
      as betaine and dimethylglycine.

PMID- 9595673
TI  - The three-for-one model for gram-negative wall growth: a problem and a possible
      solution.
AB  - The murein wall in Gram-negative bacteria is so thin that the mechanism of growth
      is necessarily complicated. From analytical data of murein components, Holtje
      suggested a model for the growth mechanism that would lead to safe wall
      enlargement. The model depended on the formation of trimers of peptidoglycan
      disaccharides linked via their pentapeptides. In the 'three-for-one' model three
      oligopeptidoglycan chains are linked to each other in the usual linkages between
      the carboxyl group of D-alanine residues and the epsilon-amino group of
      diaminopimelic acid residues; these are designated 'tail-to-tail' linkages. This
      three-chained raft is then linked to the stress-bearing wall via the formation of
      trimers, defined as three peptide chains linked together by tail-to-tail
      linkages. Then by autolyzing the oldest bonds in each trimer, the old chain is
      excised and the raft becomes part of the stress-bearing wall and the wall is
      enlarged. There is a problem with the three-for-one model in that it demands a
      precise fitting of the prefabricated raft of three crosslinked chains to a stress
      bearing chain in the wall fabric to allow the series of trimer linkages to form.
      Because the wall, when bearing stress, must be pulled into a 'honeycomb'
      structure, the end-to-end distance would be shortened. The possibility is raised
      here that the glycan chains in the stress-bearing wall are stretched to a
      sufficient degree by the cell's turgor pressure to compensate for its zig-zag
      structure; this could allow the model to function. A calculation is presented
      that assumes that the area of the pores in the fabric, called tessera, is
      maximized by the cell's turgor pressure. In this case the glycan chain must
      stretch 10% (and the end-to-end distance of peptide strands stretch 28%) so that
      the end-to-end distance of a glycan chain in the stress-bearing wall and the
      unstretched nascent wall can be the same and permit indefinite stable growth.

PMID- 9595674
TI  - The leuX-encoded tRNA5(Leu) but not the pathogenicity islands I and II influence
      the survival of the uropathogenic Escherichia coli strain 536 in CD-1 mouse
      bladder mucus in the stationary phase.
AB  - The uropathogenic Escherichia coli strain 536 carries two pathogenicity islands,
      each of which is associated with either of the tRNA genes selC or leuX,
      respectively. Growth competition in CD-1 mouse mucus between the wild-type strain
      E. coli 536, its leuX mutant 536 delta 102 and its mutant 536R3, lacking both
      pathogenicity islands but expressing a functional tRNA5(Leu), revealed a major
      impact of leuX on E. coli survival in bladder mucus. The impaired survival in CD
      1 mouse mucus observed upon deletion of the leuX gene was abolished after
      complementation with the leuX gene. The survival of bacteria in bladder mucus was
      not influenced by the presence of pathogenicity islands I and II.

PMID- 9595675
TI  - Identification, cloning and initial characterisation of FeuPQ in Brucella suis: a
      new sub-family of two-component regulatory systems.
AB  - To cause disease, Brucella species have to adapt to a range of different
      environments. Environmental sensing and adaptive responses in bacteria often
      involve the concerted action of a two-component regulatory system, consisting of
      sensor and response regulator components. Amplification and sequence analysis of
      response regulators from Brucella species identified a response regulator
      sequence with 96% similarity to Rhizobium leguminosarum FeuP. In R.
      leguminosarum, the FeuPQ two-component system is involved in the regulation of
      iron uptake. A Brucella suis feuP isogenic mutant was constructed but was not
      attenuated in the murine brucellosis model. The survival and multiplication of
      the mutant in macrophages was also unaffected. The FeuPQ regulon represents a
      newly characterised sub-family of response regulators.

PMID- 9595676
TI  - Isolation of dsRNA-associated VLPs from the strain Cryptococcus hungaricus CBS
      6569.
AB  - Double-stranded RNAs (dsRNAs) with molecular masses 1.7 and 5.0 kbp,
      respectively, were isolated from the strain Cryptococcus hungaricus CBS 6569. The
      dsRNAs were copurified with eicosahedric virus-like particles, 29 nm in diameter.
      This strain produced a protease-sensitive 'toxin' which inhibited the growth of
      strain C. hungaricus CBS 4214. The toxin had maximum activity at pH 3.7. The
      highest toxin amount was attained after a culture period of four days.

PMID- 9595677
TI  - The YGR194c (XKS1) gene encodes the xylulokinase from the budding yeast
      Saccharomyces cerevisiae.
AB  - We report the finding of a Saccharomyces cerevisiae gene necessary for growth in
      culture media with D-xylulose as the sole carbon source. This gene corresponds to
      the YGR194c open reading frame that we have previously described, and it is
      renamed now XKS1. Data bank comparisons of the protein encoded by the XKS1 gene
      showed significant homology with different xylulokinases, indicating a possible
      role in xylulose phosphorylation. The wild-type gene in a centromeric plasmid
      complemented defective growth of xks1 S. cerevisiae mutant strains in xylulose.
      By contrast, overexpression negatively influenced cell growth in this carbon
      source.

PMID- 9595678
TI  - Characterization of a spontaneous mutant of Azotobacter vinelandii in which
      vanadium-dependent nitrogen fixation is not inhibited by molybdenum.
AB  - A spontaneous mutant derivative of Azotobacter vinelandii CA12 (delta nif HDK),
      which vanadium-dependent nitrogen fixation is not inhibited by molybdenum (A.
      vinelandii CARR), grows profusely on BNF-agar containing 1 microM Na2MoO4, alone
      or supplemented with 1 microM V2O5. The expression of A. vinelandii vnfH::lacZ
      and vnfA::lacZ fusions in A. vinelandii CARR was not inhibited by 1 mM Na2MoO4,
      whereas molybdenum at much lower concentration inhibited the expression of
      vnfH::lacZ and vnfA::lacZ fusions in A. vinlandii CA12. The mutant also exhibited
      normal acetylene reduction activity in the presence of 1 microM Na2MoO4. The
      expression of A. vinelandii nifH::lacZ fusion in A. vinelandii CARR was low even
      though the cells were cultured under non-repressing conditions with urea as
      nitrogen source in the presence of Na2MoO4. The molybdenum content of A.
      vinelandii CARR cells was found to be about one-fourth that of A. vinelandii
      CA12. No nitrate reductase activity could be detected in A. vinelandii CARR when
      the cells were cultured in the presence of 10 microM Na2MoO4, whereas A.
      vinelandii CA12 exhibited some activity even with 100 pM Na2MoO4.

PMID- 9595679
TI  - Host cell protein tyrosine kinases are activated during the entry of Listeria
      monocytogenes. Possible role of pp60c-src family protein kinases.
AB  - Listeria monocytogenes is able to invade a wide range of cell types by inducing
      its own internalization. Little is known, however, about the host cell proteins
      affecting the entry process which involves triggering the host cell signal
      transduction mechanism. We report here that entry of L. monocytogenes strains
      (serotypes 4b and 1/2a) into Caco-2 cells induced tyrosine phosphorylation of
      several host cell proteins including pp60c-src substrates. Using specific
      synthetic peptide substrates, we showed that L. monocytogenes activates, as early
      as 5 min after bacteria-cell contact, the pp60c-src family-related (srcFR)
      proteins by an inlAB-dependent pathway. The activation of srcFR proteins seems to
      be crucial in the entry of L. monocytogenes into Caco-2 cells. Indeed, specific
      inhibition of the srcFR signal by herbimycin A blocked the entry of L.
      monocytogenes strains. Taken together, our data show that L. monocytogenes
      enhances cell tyrosine phosphorylations and activates the pp60c-src family
      related proteins by an inlAB-dependent pathway.

PMID- 9595681
TI  - Cloning of the thermostable phytase gene (phy) from Bacillus sp. DS11 and its
      overexpression in Escherichia coli.
AB  - Phytase hydrolyzes phytate to release inorganic phosphate, which would decrease
      the addition of phosphorus to feedstuffs for monogastric animals and thus reduce
      environmental pollution. The gene encoding phytase from Bacillus sp. DS11 was
      cloned in Escherichia coli and its sequence determined. A 560-bp DNA fragment was
      used as a probe to screen the genomic library. It was obtained through PCR of
      Bacillus sp. DS11 chromosomal DNA and two oligonucleotide primers based on N
      terminal amino acid sequences of the purified protein and the cyanogen bromide
      cleaved 21-kDa fragment. The phy cloned was encoded by a 2.2-kb fragment. This
      gene comprises 1152 nucleotides and encodes a polypeptide of 383 amino acids with
      a deduced molecular mass of 41,808 Da. Phytase was produced to 20% content of
      total soluble proteins in E. coli BL21 (DE3) using the pET22b(+) vector with the
      inducible T7 promoter. This is the first nucleic sequence report on phytase from
      a bacterial strain.

PMID- 9595680
TI  - Mercury-resistant actinomycetes from the Chesapeake Bay.
AB  - Two actinomycete strains, CHR3 and CHR28, were isolated from metal-contaminated
      sediments from Baltimore Inner Harbor. The isolates were classified as
      Streptomyces spp. Agar diffusion assays showed both isolates to be resistant to
      mercuric chloride and phenylmercuric acetate. Hybridization experiments indicated
      that genes homologous to the mercuric reductase and organomercurial lyase of
      Streptomyces lividans 1326 were present in strains CHR3 and CHR28. Strain CHR28
      grew at both low and high salt concentrations; however, strain CHR3 showed
      enhanced growth in the presence of salt, evidence of its habitat being marine or
      estuarine sediment.

PMID- 9595682
TI  - Sweet and bitter taste discrimination in primates: scaling effects across
      species.
AB  - The adaptive nature of taste discrimination has been questioned on the basis that
      marked differences in taste thresholds for soluble sugars across mammals may not
      correspond to distinct dietary tendencies and further imply inaccurate prediction
      of the energetic value of food. Appropriate models of the evolution of taste,
      however, require not only consideration of adaptations to diet but also
      recognition of phylogenetic and allometric effects. Here, we analyse these
      factors in primates exhibiting various diets and covering a wide range of body
      weights. Taste thresholds for sucrose and fructose are negatively related to body
      weight overall but are commonly similar in closely related species irrespective
      of dietary specialisations. By contrast, major interspecific differences in the
      discrimination of quinine hydrochloride are observed in the absence of any
      allometric effect. We propose that this asymmetrical differentiation of sweet and
      bitter taste discrimination reflects divergent evolutionary trends for meeting
      energy requirements and for avoiding noxious substances.

PMID- 9595683
TI  - Colour cues for leaf food selection by long-tailed macaques (Macaca fascicularis)
      with a new suggestion for the evolution of trichromatic colour vision.
AB  - Leaf colour, size and toughness were investigated in five plant species important
      in the diet of Macaca fascicularis in Singapore. Leaf colour and size were
      examined as potential visual cues for food selection, whereas toughness mirrored
      fibre content, the inverse of food quality. As leaves matured, they changed
      colour and toughened. Leaf lightness and yellowness were strongly negatively
      correlated with toughness, but variation in both the red-green axis of the CIE
      Lab colour space and leaf size were not. Leaves selected as food by the macaques
      were distinguished by being very light, yellow to slightly green. Some leaves
      were dappled with red. The literature suggests that these leaves are relatively
      rich in protein without being tough and therefore would be sought after by
      primates. We argue that leaf colour is an important indicator of the nutritive
      value of leaves. Trichromatic vision is an important advantage in finding those
      palatable leaves that are dappled red. These would appear dark to dichromatic
      primates and be deceptive by making leaves look older (lower in quality) than
      they actually are. This would decrease the perceived window of feeding
      opportunity for such primates who would be at a disadvantage in trying to find
      these leaves. It is possible that trichromatic vision in catarrhine primates may
      have originally evolved for the detection of red coloration in the leaves of
      shade-tolerant tropical plants, enabling the better exploitation of a food
      resource.

PMID- 9595684
TI  - Changes in range use of Geoffroy's tamarins (Saguinus geoffroyi) associated with
      habituation to observers.

PMID- 9595685
TI  - Pair-bonding, female aggression and the evolution of lemur societies.
AB  - Lemur societies have been described as convergent with those of anthropoids,
      including Papio-like female-bonded multi-male groups. Recent research, however,
      shows at least 5 pair-bonded species among the Lemuridae and Indriidae. Three
      more, Eulemur mongoz, Eulemur fulvus and Varecia variegata, have societies
      combining aspects of pairing with aspects of troop life. The best-known female
      bonded societies, those of Lemur catta, Propithecus diadema edwardsi and
      Propithecus verreauxi, may be assemblages of mother-daughter dyads, capable of
      high aggression towards other females, but derived from more solitary female
      ancestors, perhaps also living as pairs. The internal structure of such lemur
      groups differs from the more extensive kin groups of catarrhines. This in turn
      may relate to the lemurs' level of social intelligence and to lemur female
      dominance over males.

PMID- 9595686
TI  - Infanticide by a female black lemur, Eulemur macaco, in disturbed habitat on Nosy
      Be, north-western Madagascar.

PMID- 9595687
TI  - The mechanics of food reduction in Tarsius bancanus. Hard-object feeder, soft
      object feeder or both?
AB  - The high-cusped, almost tritubercular teeth of Bornean tarsiers are used to
      reduce a wide variety of animal food. Prey is characteristically consumed entire,
      no parts being discarded. This paper attempts to identify the dental
      characteristics which permit tarsiers to reduce food substrates with widely
      varying mechanical properties and to assess whether reduction of some substrates
      incurs greater costs for tarsiers. Finite elements stress analysis (FESA)
      modelling is used to compare the effectiveness of tarsier and human teeth in
      reducing three types of food substrate habitually reduced by both species. Bone
      is taken as the exemplar of strong, stiff substrates, skin as the exemplar of
      substrates low in both stiffness and strength, and tendon as the exemplar of low
      stiffness but strong substrates. The parameters used to measure performance are
      the work that must be done to bring tensile stresses to the point where tensile
      failure will be initiated and the bite-force required to do so. Human molars
      perform best in reducing bone, and tarsier molars in reducing skin. Neither
      perform as well in reducing tendon. Blunt, bunodont human molars perform slightly
      better than the high-cusped molars of tarsiers in reducing bone, but tarsier
      molars perform much better than human molars in inducing failure in skin and are
      also considerably better in reducing tendon. While the reduction effectiveness of
      human molars is greatly affected by substrate properties, the high cusps of
      tarsier teeth enable them to reduce foodstuffs of widely differing properties
      reasonably well. Scaling factors undoubtedly influence selection for cusp height,
      since high cusps are a prerequisite of effective crack propagation in food
      substrates by small animals. Microwear features do not show a consistent pattern
      where striations are associated with surface-parallel loads but pitting with
      surface-normal loads (at least as modelled by FESA). However, FESA modelling of
      the magnitude of applied forces and relative food/tooth displacement during
      occlusion suggest that the type of wear found in different regions is governed by
      the combined influences of relative tooth/food displacement and food/tooth
      reaction force. Pitting is associated with low levels of food/tooth displacement
      but high levels of reaction force, striation with high levels of displacement but
      low levels of force, and stripping or gouging of enamel with high values of both
      displacement and reaction force.

PMID- 9595688
TI  - Size dependence in prosimian locomotion and its implications for the distribution
      of body mass.
AB  - The mechanical requirements for arboreal life are reviewed and the constraints
      which these requirements impose on the body of a prosimian are defined. The
      mechanical necessities can be fulfilled only by animals which possess the
      appropriate morphological characters. It is incorrect to refer to these
      morphological traits directly as 'adaptations'. Instead their a priori existence
      must be considered as the precondition for the acquisition of a certain life
      style. Once such a life-style has been acquired, a strong selective pressure acts
      towards a further refinement of such 'adaptations' or 'pre-adaptations'.
      Postcranial morphology must be seen in a context of following natural laws and is
      strictly related to the mechanics of posture and locomotion. The traits
      emphasised and explained here are body proportions--specifically the relative
      lengths of body segments and the distribution of (muscle) mass on these segments.

PMID- 9595689
TI  - The impact of genetics on the conservation of Malagasy lemur species.

PMID- 9595691
TI  - Comparison of genetic variability in wild insular and mainland populations of
      Eulemur macaco: implications for conservation strategy.
AB  - DNA fingerprinting analysis was used to investigate genetic variability within
      and between three wild populations of Eulemur macaco living on two islands and on
      the mainland. The analyses revealed that the genetic variability of the
      population from the smaller island was, as expected, lower than that from the
      larger island. Surprisingly, on the larger island the genetic variability was
      greater than on the mainland. These results, in agreement with those previously
      obtained from blood markers, are discussed in relation to the history of these
      populations. In addition, the study suggests that settlement of the smallest
      island was not only by animals originating from the mainland, as previously
      proposed on the basis of blood marker data, but also by lemurs from the nearby,
      larger, island. Evidence is presented that reliable information about population
      structure can be derived only from studies using different genetic markers. This
      information is important to enable appropriate conservation programmes to be
      designed.

PMID- 9595690
TI  - Comparison of the genetic diversity of wild and captive groups of Microcebus
      murinus using the random amplified polymorphic DNA method.
AB  - Continued survival of most animal species depends on population management and
      active protection. It is generally agreed that, in order to avoid extinction of
      endangered species, ex situ and in situ conservation must be developed in tandem.
      However, even though many recommendations have been put forward to promote the
      survival of captive populations, some rapidly become extinct due to loss of
      genetic diversity (drift effect). Genetic markers, such as random amplified
      polymorphic DNA (RAPD) markers, can be applied to rapid testing of many
      individuals. They also permit analysis of very small amounts of DNA, when small
      species such as mouse lemurs (Microcebus) are to be tested. Using RAPD markers,
      we compare genetic diversity in four captive groups of Microcebus murinus to that
      in a sample of 70 wild mouse lemurs. Following the principles of Mendelian
      inheritance, each amplified fragment of DNA may be considered as a 'locus' (or an
      amplifying site). The series of bands amplified by a particular primer in any
      individual is referred to as the individual's 'profile'. We tested 5 primers, or,
      in the above terms, we studied 98 different 'loci'. Results showed that the
      captive groups had lost genetic information with respect to the wild sample.
      Among the four captive groups, the loss of genetic diversity varied according to
      their number of founders and/or the management of their captive reproduction. Our
      study of polymorphism permitted us to establish tools for the genetic management
      of captive breeding, and for the determination of paternity which frequently give
      better results than behavioural studies; and simulation of introductions or
      departures of individuals in one very monomorphic group permitted estimation of
      future increases in its genetic diversity.

PMID- 9595692
TI  - Evolutionary history of lorisiform primates.
AB  - We integrate information from the fossil record, morphology, behavior and
      molecular studies to provide a current overview of lorisoid evolution. Several
      Eocene prosimians of the northern continents, including both omomyids and
      adapoids, have been suggested as possible lorisoid ancestors, but these cannot be
      substantiated as true strepsirhines. A small-bodied primate, Anchomomys, of the
      middle Eocene of Europe may be the best candidate among putative adapoids for
      status as a true strepsirhine. Recent finds of Eocene primates in Africa have
      revealed new prosimian taxa that are also viable contenders for strepsirhine
      status. Plesiopithecus teras is a Nycticebussized, nocturnal prosimian from the
      late Eocene, Fayum, Egypt, that shares cranial specializations with lorisoids,
      but it also retains primitive features (e.g. four premolars) and has unique
      specializations of the anterior teeth excluding it from direct lorisiform
      ancestry. Another unnamed Fayum primate resembles modern cheirogaleids in dental
      structure and body size. Two genera from Oman, Omanodon and Shizarodon, also
      reveal a mix of similarities to both cheirogaleids and anchomomyin adapoids.
      Resolving the phylogenetic position of these Africa primates of the early
      Tertiary will surely require more and better fossils. By the early to middle
      Miocene, lorisoids were well established in East Africa, and the debate about
      whether these represent lorisines or galagines is reviewed. Neontological data
      are used to address the controversial branching sequences among extent lorisid
      clades. Data from the skin and scent glands, when integrated with other lines of
      evidence, suggest that Asian and African lorisines share a common lorisine
      ancestry. The hypothesis of an African clade containing both pottos and galagos
      to the exclusion of Asian lorisines is less tenable. True galagines are found in
      the fossil record of Namibia, while true lorisines are known from the Miocene of
      Asia. The hypothetical branching sequences can be integrated with behavioral and
      morphological features to develop an adaptive model of lorisoid divergence. By
      specializing on two different foraging modes early in their radiation, lorisines
      and galagines subsequently underwent a chain of integrated evolutionary changes
      eventually having an impact on many components of locomotor behavior, anatomy,
      physiology, reproduction, life history, and social behavior. Ongoing evolutionary
      studies of extant galagines are illuminating population phenomena and processes
      of speciation in an ecological context.

PMID- 9595693
TI  - Acoustically dimorphic advertisement calls separate morphologically and
      genetically homogenous populations of the grey mouse lemur (Microcebus murinus).
AB  - Sexual advertisement calls of male mouse lemurs from two neighbouring demes in a
      dry deciduous forest of western Madagascar were recorded during the breeding
      season. Demes were located about 1.5 km apart with no geographic barrier between
      them. They were characterised morphometrically and genotyped by RAPD
      fingerprinting. According to univariate and multivariate statistical analysis,
      demes differed neither in body measurements, nor in the banding patterns produced
      by RAPD fingerprinting. The acoustic pattern of the advertisement call, however,
      showed significant differences: Six variables of the frequency and time domain
      differed between the demes. Discriminant function analysis revealed that one
      variable, total call duration, was sufficient to classify more than 89% of the
      calls correctly to the corresponding deme. We postulate that these differences
      are comparable to dialects in birds, because demes were morphologically and
      genetically indistinguishable and no barrier prevented genetic exchange between
      them. Possible explanations for the emergence of dialects in a prosimian species
      are outlined.

PMID- 9595694
TI  - Speciation in the lesser galagos.
AB  - Species and their origins remain one of the outstanding enigmas of evolutionary
      biology. Many different views of the problem exist, but few have concrete
      predictions that open the problem to investigation. This study formalises
      predictions arising from the Recognition Concept of species (RC) and the
      Organization Theory of Speciation (OTS), and applies them to the pattern
      demonstrated by the lesser galago radiation. The RC and OTS are in agreement that
      one of the primary adaptive responses during animal speciation events involves
      the system of sexual recognition and reproduction, and indeed the lesser galago
      taxa show significant divergences in their communication systems relating to
      specific-mate recognition. On the other hand, only the RC predicts a concomitant
      adaptive response to the ecological conditions prevailing during speciation, and
      there are strong indications of shifts in habitat preference among these taxa.
      The predictions of the RC are supported above those of the OTS.

PMID- 9595695
TI  - Toroidal coil counter-current chromatography study of the mass transfer rate of
      proteins in aqueous-aqueous polymer phase system.
AB  - The cause of excessive band broadening of protein samples in polymer phase
      partitioning by counter-current chromatography (CCC) was investigated. A simple
      rotary device was constructed to measure the mass transfer rates of five samples
      including potassium dichromate, methylene blue, lysozyme, ovalbumin and human
      serum albumin. The results indicated that the mass transfer rates of these
      samples are closely correlated with their molecular masses: the higher the
      molecular mass, the lower the mass transfer rate. These findings are also
      consistent with the partition efficiencies of these samples in the same solvent
      system by CCC. The beneficial effect of the Coriolis force demonstrated in
      protein separations by the toroidal coil centrifuge may be reasonably explained
      on the basis of the mass transfer resistance of protein molecules through the
      interface: we speculate that when the Coriolis force acts parallel to the
      effective coil segment it can produce large interfacial areas by dispersing the
      mobile phase into the stationary phase, thus accelerating the mass transfer rate
      of protein samples.

PMID- 9595696
TI  - Determination of phenylurea herbicides in water samples using online sorptive
      preconcentration and high-performance liquid chromatography with UV or
      electrospray mass spectrometric detection.
AB  - A recently developed method for the extraction of organic micropollutants from
      aqueous samples based on sorptive enrichment in columns packed with 100%
      polydimethylsiloxane (PDMS) particles was coupled on-line with HPLC analysis. The
      sorptive enrichment procedure originally developed for relatively nonpolar
      analytes was used to preconcentrate polar phenylurea herbicides from aqueous
      samples. PDMS extraction columns of 5, 10 and 25 cm were used to extract the
      herbicides from distilled, tap and river water samples. A model that allows
      prediction of retention and breakthrough volumes is presented. Despite the
      essentially apolar nature of the PDMS material, it is possible to concentrate
      sample volumes up to 10 ml on PDMS cartridges without losses of the most polar
      analyte under investigation, fenuron. For less polar analytes significantly
      larger sample volumes can be applied. Since standard UV detection does not
      provide adequate selectivity for river water samples, an electrospray (ES)-MS
      instrument was used to determine phenylurea herbicides in a water sample from the
      river Dommel. Methoxuron was present at a level of 80 ng/l. The detection limit
      of the current set-up, using 10 ml water samples and ES-MS detection is 10 ng/l
      in river water samples. Strategies for further improvement of the detection
      limits are identified.

PMID- 9595697
TI  - High-performance capillary electrophoresis for in-process control in the
      production of antithrombin III and human clotting factor IX.
AB  - Antithrombin III (ATIII) and factor IX (FIX), two proteins from the clotting
      cascade, were investigated in parallel experiments, using capillary gel
      electrophoresis and capillary isoelectric focusing. The results from these
      experiments were compared with the results obtained from sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and slab gel isoelectric focusing.
      In the case of ATIII, capillary gel sieving showed comparable results to SDS-PAGE
      with the added advantage of the shorter time required for analysis. By optimizing
      capillary isoelectric focusing (cIEF), a separation of the ATIII isoforms was
      achieved. In the case of FIX, capillary gel electrophoresis (SDS-CE) of a FIX
      preparation gave similar results to those obtained by size-exclusion high
      performance liquid chromatography and SDS-PAGE, but turned out to be less
      sensitive in detecting protein impurities at low concentrations. The
      microheterogeneity of this protein was shown by using cIEF.

PMID- 9595698
TI  - Capillary electrophoretic separation of cationic porphyrins.
AB  - Cationic porphyrins have a wide variety of uses including those as nucleic acid
      binding and cleaving agents, as potential pharmacological agents, as electron
      donor/acceptors in intramolecular electron transfer processes and as analytical
      reagents. Herein, we report the separation of cationic porphyrins by capillary
      electrophoresis on fused silica in phosphate buffer at pH 2-5. The porphyrins
      studied in this work were synthesized from alkylation of the parent
      tetrapyridylporphyrin (TPyP) to give various pyridinium porphyrins. For example,
      methylation of TPyP gives a mixture of the mono-, cis-di-, trans-di-, tri- and
      tetramethylated porphyrins [e.g., 5,10,15,20-tetrakis(N-methyl-4-pyridiniumyl)
      21H,23H-p orphyrin, TMPyP(4)]. Capillary electrophoresis on a synthetic mixture
      showed separation of four of these compounds. Mixtures after alkylation with
      iodopropionic acid and bromopropylamine were also separated. The cis-di- and
      trimethylated TMPyP derivatives were separated on a small preparative scale by
      centrifugal partition chromatography. Capillary electrophoresis was also used to
      separate metallo TMPyP(4) complexes including those of cobalt, copper, iron,
      manganese, palladium, tin, vanadium and zinc. The conformational isomers
      (atropisomers) of 5,10,15,20-tetrakis(N-methyl-2-pyridiniumyl)-21H,23H-p
      orphyrin, TMPyP(2), were also separated. Net charge, molecular mass and molecular
      shape all contribute to the differential retention of cationic porphyrins under
      capillary electrophoresis conditions. Additional factors affecting the
      separations, including aggregation and protonation of the porphyrins, were probed
      by evaluating the separation of TMPyP(4) and its butyl and octyl analogs as a
      function of solution conditions. Cationic porphyrins are difficult to separate
      using traditional chromatographic methods; capillary electrophoresis and
      centrifugal partition chromatography provide excellent new techniques for
      separation of this class of compounds.

PMID- 9595699
TI  - How children reason about ability from report card grades: a developmental study.
AB  - Elementary school students were interviewed to see how they reason about ability
      in the context of report card grades. Eighty-four 2nd, 4th, and 6th graders were
      presented with hypothetical children's report card grades for performance and
      effort and were asked to compare the children's "smartness." Four age-related
      levels of reasoning about ability were identified, in accordance with findings
      from past research. However, 6th graders did not use the expected highest levels
      of reasoning, which involve covariation of performance and effort information;
      rather, their reasoning emphasized the efficacy of effort. Reasons for
      differences between the present and previous findings are discussed.

PMID- 9595700
TI  - The effects of parents' assistance on middle school students' problem solving and
      achievement.
AB  - In this study the authors tested whether children's aptitudes in science were
      advanced in areas in which cognitive supports were generally present,
      particularly through interaction with more capable individuals. Mothers assisted
      their 7th-grade children in science activities. Differences in parent-child
      interaction were hypothesized to account for children's performance across 3
      science tasks that differed in difficulty. A cooperative problem-solving style of
      interaction was identified through factor analysis. This interaction style was
      correlated significantly with the child's intellectual performance not only in
      the science tasks but also in school achievement. Development of science and
      other aptitudes in the context of activity variables that help bridge home and
      school cultures are discussed.

PMID- 9595701
TI  - Developmental variations in factors related to initial and increased levels of
      adolescent drug involvement.
AB  - The impact of maternal and adolescent factors on initial and increased levels of
      drug use by adolescents was examined in two groups of adolescents: 210 younger
      adolescents (ages 12-14 at initial assessment) and 199 older adolescents (ages 15
      18). The adolescents and their mothers were interviewed at 2 points in time, 3
      years apart. The results indicated that adolescent unconventionality is a crucial
      determinant for both initial and increased levels of drug use for both age
      groups, but intrapsychic distress is more important for the younger adolescent's
      initial use. Lack of maternal attachment and poor control techniques were
      associated with initial levels of drug use for both groups. However, the mother
      child relationship and models of the mother's unconventionality had a greater
      impact on the older than on the younger group's increased involvement.
      Interactive results suggest that adolescents from both age groups who are well
      adjusted can offset the potential risks of maternal models of drug use.

PMID- 9595702
TI  - Effects of age, gender, and participation in volunteer activities on the
      altruistic behavior of Chinese adolescents.
AB  - Possible associations of gender, age, and participation in volunteer activities
      with altruistic behavior of Chinese adolescents were investigated. A
      representative sample of 1,105 Hong Kong Chinese adolescents (457 boys, 648
      girls) were recruited from 20 schools. Results of multiple regression analyses
      indicated that there was a positive age effect on altruistic behavior. In
      addition, a positive association between self-reported altruistic behavior and
      frequency of participation in volunteer activities was found. No gender
      differences were found.

PMID- 9595703
TI  - Satisfaction with early relationships with parents and psychosocial attributes in
      adulthood: which parent contributes more?
AB  - The relationships between perceived satisfaction with early relationships with
      parents and adults' psychosocial attributes were addressed in this study. The
      participants were 928 medical students (37% women) who completed a set of
      personality questionnaires. The results indicated that perceived satisfaction
      with the mother in childhood was significantly associated with less intensity and
      chronicity of loneliness, less depression, less anxiety, a less negative view of
      stressful life events, higher self-esteem, and more satisfaction with peer
      relationships. No significant association was found between perceived
      satisfaction with the father and these personality measures. The results are
      discussed in the context of attachment theory and internal working models.

PMID- 9595704
TI  - The effect of quality of family interaction and intergenerational transmission of
      values on sexual permissiveness.
AB  - Quality of family interaction as a moderator of the relation between mothers and
      their adolescent children's sexual permissiveness was examined. Mothers were
      expected to be able to influence their children's sexual standards, but this
      effect was expected to be stronger when the family interaction was characterized
      by mutual understanding and respect. This hypothesis was tested by means of
      multiple-group structural equation modeling, with a sample of 323 adolescent
      mother pairs that were representative of the Brighton and Hove (UK) area. The
      adolescents were 14 to 18 years old. The results supported our hypothesis that
      intergenerational transmission of values benefits from good mother-child
      relations. In addition, we found that socioeconomic status was less strongly
      related to adolescent permissiveness and age was more strongly related in high
      quality of interaction groups than in low quality of family interaction groups.
      Implications of the study are discussed.

PMID- 9595705
TI  - Parental discipline and behavior problems in young children.
AB  - The relationship between parenting practices and behavior problems in very young
      children was investigated via the Parent Behavior Checklist (PBC; Fox, 1994).
      Results indicated that parents' use of verbal and corporal punishment was the
      strongest predictor of reported behavior problems, accounting for 20% of overall
      variance and 13% of unique variance. Results for parental nurturing and
      expectations were mixed and suggest an indirect effect. Several demographic
      variables were also predictive of behavior problems. Implications for Patterson's
      (1986) model of the development of antisocial behavior and for the use of parent
      assessment as a screening tool for preventive interventions are discussed.

PMID- 9595707
TI  - Photophysics of the cationic 5,10,15,20-tetrakis (4-N-methylpyridyl) porphyrin
      bound to DNA, [poly (dA-dT)]2 and [poly (dG-dC)]2: interaction with molecular
      oxygen studied by porphyrin triplet-triplet absorption and singlet oxygen
      luminescence.
AB  - Interaction between molecular oxygen and the cationic free-base 5,10,15,20
      tetrakis (4-N-methylpyridyl) porphyrin (H2TMpyP4+) complexed with [poly (dA
      dT)]2, [poly (dG-dC)]2 and calf thymus DNA, has been monitored in air-saturated
      heavy water solutions through porphyrin triplet-triplet absorption and singlet
      oxygen luminescence. Three different rate constants of porphyrin triplet state
      quenching have been found which correspond to different accessibilities of
      molecular oxygen to porphyrins embedded in the duplexes. The longest triplet
      state lifetime (30 microseconds), found for porphyrin bound to [poly (dG-dC)]2,
      corresponds to molecules well protected from oxygen. This supports the hypothesis
      of an intercalative binding mode of the porphyrin between GC base-pairs ('type A'
      sites). The fraction fT delta of the porphyrin triplet states quenched by
      molecular oxygen with singlet oxygen generation, is unity. In [poly (dA-dT)]2
      porphyrin complexes, two sites ('type B' and 'C' sites of interaction) are
      involved, yielding very different triplet state lifetimes (5.5 microseconds and
      20.5 microseconds) and efficiencies of singlet oxygen generation (fT delta = 0.50
      and 0.82). The fT delta decreases can likely be explained in terms of competition
      between energy and electron transfer from the porphyrin excited triplet state to
      molecular oxygen. All three types (A, B and C) of interaction sites can be
      expected in porphyrin-DNA complexes.

PMID- 9595706
TI  - Estimation of the effect of increasing UVB exposure on the human immune system
      and related resistance to infectious diseases and tumours.
AB  - Exposure to UV light has, besides some beneficial effects (vitamin D production),
      many harmful effects on human health. UVB irradiation has been shown to suppress
      both systemic and local immune responses to a variety of antigens, including some
      microorganisms. However, it is still not known whether such immunomodulating
      effects may lead to an increase in the number and severity of certain tumours
      and/or infections in humans. We report herein the data provided by a project that
      was funded by the European Union (Programme Environment), and that was aimed at
      the estimation of the risk associated with increased UVB exposure due to ozone
      depletion regarding the deleterious effects on the immune system and related
      resistance to tumours and infections in humans. The data, obtained by the
      different research groups involved, were assembled and used to calculate for the
      first time a risk assessment for increased environmental exposure to UVB in human
      subjects.

PMID- 9595708
TI  - Photoprotector capacity of lichen metabolites assessed through the inhibition of
      the 8-methoxypsoralen photobinding to protein.
AB  - Lichens produce a diversity of phenolic compounds, some of which efficiently
      absorb ultraviolet radiation, 8-Methoxypsoralen (8-MOP), commonly used in the
      treatment of psoriasis, binds irreversibly to proteins in the presence of
      ultraviolet radiation by a mechanism that is not well established. In this paper
      we demonstrate the photoprotector capacity of three phenolic compounds-pannarin,
      1'chloropannarin and atranorin-through the inhibition of 8-MOP-human serum
      albumin (HSA) photobinding. The method measures the UV-filtering capacity of
      lichen compounds by means of a double-tube compartment (thus, solubility and
      interaction with the reaction medium is avoided). Photobinding was determined by
      measuring the radioactivity of mixtures containing 8-(methyl-3H) MOP and HSA
      irradiated at 360 and 310 nm in the presence of increasing concentrations of
      lichen phenolics. Pannarin, l'-chloropannarin and atranorin at a concentration of
      10 mM and irradiated at 360 nm, inhibited photobinding to HSA by 40.4%, 31.7% and
      20.1% respectively. Pannarin (10 mM) irradiated at 310 nm inhibited the
      photobinding by 35.2%. The participation of singlet oxygen and hydroxyl radicals
      was demonstrated in the photoreaction process.

PMID- 9595709
TI  - Photoinactivation of amelanotic and melanotic melanoma cells sensitized by
      axially substituted Si-naphthalocyanines.
AB  - The photosensitizing activity of the new far-red absorbing naphthalocyanine SiNc
      [OSi (n-C10H21)3] [OSi(CH3)2(CH2)3N(CH3)2], (DAP-SiNc), and of its analogue SiNc
      [OSi(i-C4H9)2(n-C18H37)]2, (IsoBO-SiNc), was studied with two cell variants of
      B16 melanoma, the amelanotic clone B78H1 and the highly pigmented B16F1 cells.
      Upon excitation with a 776 nm diode laser, DAP-SiNc appeared to be a markedly
      more efficient photosensitizer than isoBO-SiNc. The higher photoefficiency of DAP
      SiNc was likely to reflect its accumulation in significantly larger amounts by
      both cell types, as well as a much smaller tendency to undergo aggregation when
      bound to the cells. In any case, melanotic cells were less sensitive to the
      photoinactivating action of DAP-SiNc: the protective action of melanin was a
      consequence of an optical filtering of the 776 nm light and an appreciable
      shortening of the DAP-SiNc triplet lifetime (40 microseconds for the amelanotic
      vs. 17 microseconds for the melanotic cells). Functional and morphological
      studies on irradiated cells showed that cell death due to DAP-SiNc
      photosensitization was mainly correlated with the modification of targets located
      in the lysosomes and the cytoplasmic membrane.

PMID- 9595710
TI  - Eradication of Acinetobacter baumannii by photosensitized agents in vitro.
AB  - The photodynamic effects of photosensitizers on Acinetobacter baumannii were
      studied. These Gram negative bacteria have recently been implicated in various
      infections, mainly acquired in hospitals. They have outstanding characteristics
      of multidrug high resistance to antimicrobial agents. The best photodynamic
      effect was obtained when A. baumannii cultures were treated with light activated
      deuteroporphyrin (Dp) at a concentration of 34 mumoles l-off and polymyxin
      nonapeptide (PMNP) at a concentration of 200 mumoles l-1. At these concentrations
      the culture in brain heart infusion (BHI) broth was found to be sterile after l h
      of treatment. Some inhibition was also obtained under the same conditions with Cd
      texaphyrin (Cd-Tx) in the presence of PMNP. Treatment with various other
      photosensitizers in the presence of PMNP exhibited only marginal antibacterial
      activity. The cationic photosensitizer tetra-methylpyridyl porphine (TMPyP) did
      not exhibit any photodynamic effect on A. baumannii when illuminated during its
      growth in BHI broth. Bacteria grown in nutrient broth or suspended in saline and
      treated by TMPyP resulted in a significant photoinactivation by the sensitizer
      alone even in the absence of PMNP. It was found that a high concentration of the
      proteins present in BHI or in serum prevent TMPyP from acting as a
      photosensitizer against A. baumannii. Bovine serum albumin at the same high
      protein concentration prevents Dp (in the presence of PMNP) to act as a
      photosensitizer. The anionic photosensitizer tetra-sulfonatophenyl porphine
      (TPPS4) did not show any photodynamic effect in high or low protein media. In
      this study it was found that despite the high resistance of the Acinetobacter
      baumannii to antibiotics, these bacteria can be significantly photoinactivated by
      treatment with either Dp + PMNP or TMPyP in low protein content environments.
      When the protein concentration is high photoinactivation efficiency depends on
      the type of protein present in the medium.

PMID- 9595711
TI  - Photodegradation and phototoxicity studies of furosemide. Involvement of singlet
      oxygen in the photoinduced hemolysis and lipid peroxidation.
AB  - The phototoxic diuretic drug furosemide (1), a 5-(aminosulfonyl)-4-chloro-2-[(2
      furanylmethyl)-amino] benzoic acid is photolabile under aerobic and anaerobic
      conditions. Irradiation of a methanol solution of 1 under oxygen produces
      photoproducts 2, 3, 4 and singlet oxygen, while under argon the photoproducts 2
      and 4 were isolated. A peroxidic unstable photoproduct was detected during the
      photolysis under oxygen atmosphere. The formation of singlet oxygen by photolysis
      of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-mass), furfuryl alcohol
      and 1,3-cyclohexadiene-1,4-diethanoate (HPLC) as 1O2 scavengers and by the
      histidine test. Furosemide was screened in vitro at different concentrations for
      UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and
      absence of different radical scavengers, singlet oxygen and hydroxyl radical
      quenchers. However, furosemide photosensitized the peroxidation of linoleic acid,
      as monitored by the UV-detection of dienic hydroperoxides and it also
      photosensitized the oxidation of histidine. The photodegradation was catalyzed in
      the presence of human serum albumin. Studies on peripheral blood mononuclear and
      polymorphonuclear cells (lymphocytes and neutrophils) demonstrated no
      phototoxicity on these cell lines.

PMID- 9595712
TI  - Effects of simulated solar radiation on type I and type III collagens,
      collagenase (MMP-1) and stromelysin (MMP-3) gene expression in human dermal
      fibroblasts cultured in collagen gels.
AB  - Understanding the mechanisms responsible for photodamage to the skin is most
      important for dermatology. 3-D cultures have been used as tools to mimic the in
      vivo situation for several years. We irradiated such a system containing human
      dermal fibroblasts cultured in collagen gels, a well-known model considered to be
      a dermal equivalent, which reproduces the interaction between cells and the
      surrounding extracellular matrix. The effects of solar irradiation (315-800 nm)
      on the steady-state levels of the mRNAs of extracellular matrix components (type
      I and III collagens) and their degrading enzymes (interstitial collagenase, MMP-1
      and stromelysin 1, MMP-3) were measured. Exposure to low levels of solar
      radiation (0-10 J cm-2 in the UVA, i.e. suberythemal UVA doses) caused a
      transient decrease in type I procollagen mRNA, an increase in MMP-mRNA, and no
      change in type III procollagen mRNA steady-state levels. These results describe
      the early changes in the connective tissue of the skin following exposure to low
      level solar stimulation, and may help explain the long-term changes in
      photodamaged skin.

PMID- 9595713
TI  - [Assessment of short-term effects of awareness programs and pravastatin therapy
      on subjects from private clinics at high risk for cardiovascular disease].
AB  - PURPOSE: To evaluate short-term efficacy of awareness programs (AP) in reducing
      coronary heart disease risk factors (CHDRF). METHODS: High risk
      hypercholesterolemic patients were divided in 2 groups during 16 weeks. Group A
      (n = 417, 54.3 +/- 10.0 years, 55% males) received verbal and written orientation
      on CHDRF control, and group B (n = 180, 54.4 +/- 10.9 years, 45% males) received
      only verbal orientation. All participants received pravastatin 10 mg q.d. for 12
      weeks. The evolution of body weight, arterial pressure, lipid profile, Castelli's
      I and II indexes (TC/HDL and LDL/HDL), and Framingham scores were evaluated.
      RESULTS: At baseline, A had a lower HDL-C (40.0 +/- 11.0 vs 43.0 +/- 11.0 mg/dl,
      p = 0.013) and a higher index I (8.2 +/- 3.0 vs 7.6 +/- 2.3, p = 0.008) than B.
      After 16 weeks, A had greater change than B in TC (-28.0 vs -25.0, p < 0.05), LDL
      C (-29.0 vs -27.6, p < 0.05), HDL-C levels (+13.7 vs +10.8, p < 0.05) and in the
      Castelli's Index (-39.0 vs -33.0; p < 0.05). In both groups pravastatin use
      potentialized the effects of diet on the lipid profile. CONCLUSION: The AP seemed
      to be more effective than verbal orientation alone in CHDRF reduction at short
      term.

PMID- 9595714
TI  - [Risk factors for atherosclerosis in children: an epidemiologic study].
AB  - PURPOSE: To obtain a profile of risk factors for coronary atherosclerosis in a
      pediatric population from Bento Goncalves, Rio Grande do Sul, from May 1990 to
      June 1991. METHODS: One thousand five hundred and one children with ages from 6
      to 15 years were studied to assess serum cholesterol levels and their association
      with other risk factors, such as arterial hypertension, obesity and family
      history of cardiovascular disease. RESULTS: Four hundred and twenty (27.98%)
      children showed cholesterol levels over 180 mg%; 75 (5%) had systolic
      hypertension and 48 (3.20%) diastolic hypertension. The family history was
      important to search for risk factors such as hypercholesterolemia, but did not
      exclude risk factors when negative. One hundred and thirty six (9.06%) children
      showed hipetriglyceridemia; 155 (10.33%) presented LDL-cholesterol above 130 mg%
      and showed a strong association with hypercholesterolemia. Obesity was present in
      111 children, but none showed a major prevalence of hypercholesterolemia.
      CONCLUSION: Risk factors for atherosclerosis are present in children and their
      search should be performed, independent of family income, family history, age and
      sex. The pediatrician must have a significant role in this setting.

PMID- 9595715
TI  - [Maximal functional capacity and diastolic function in patients with
      cardiomyopathy due to Chagas' disease without congestive heart failure].
AB  - PURPOSE: To identify early cardiac dysfunctions in asymptomatic patients with
      Chagas' cardiomyopathy. METHODS: We studied 38 male individuals: control group
      consisting of 20 sedentary normal individuals and Chagas' group, of 18
      asymptomatic patients with Chagas' disease, with suggestive electrocardiographic
      alterations and normal fractional shortening (FS) on echocardiogram. Both groups
      were submitted to evaluation of the maximal functional capacity, with
      measurements of maximal O2 consumption (VO2max), O2-pulse rate (PO2max), maximal
      ventilation (VEmax), maximal heart rate (HRmax), and anaerobic threshold of the
      VO2max (VO2-AT). Left ventricular diastolic function was evaluated by
      conventional echocardiography (E wave, A wave and E/A ratio). RESULTS: No
      significant differences occurred between the two groups with regard to FS (p =
      0.212) and age means (p = 0.060). The 2 groups were significantly different (p <
      0.001) regarding the parameters VO2max, PO2max, VEmax, HRmax and VO2-AT, E wave
      and E/A ratio. There was no difference (p = 0.520) in A wave. CONCLUSION:
      Impaired ventricular function may account for the above mentioned differences, a
      consequence of both systolic and diastolic dysfunctions.

PMID- 9595716
TI  - [Mesoscopic study of the mitral valve and its fibrous ring].
AB  - PURPOSE: To study the spatial arrangement of the fibrous elements that form the
      leaflets of the mitral valve and its fibrous ring. METHODS: The study of 20 human
      adult hearts, of both sexes, fixed in 10% formaldehyde solution was made. The
      mitral valves with their fibrous rings and small parts of the adjacent atrial and
      ventricular muscles were removed. Part of this material was embedded in paraffin
      and cut serially at a thickness of 40 microns and stained by Azan's trichrome and
      by resorcin-fuccin and another was dissected under stereoscope in order to verify
      the arrangement of the myocardial bundles at the level of the fibrous ring.
      RESULTS: It was observed that the fibrous ring is consisted of collagenous fibers
      which involved in an incomplete form the atrioventricular ostium, as they were
      absent in the anteromedial region of the ostium. The leaflets were made of
      collagenous fibers disposed parallel to the long axis of the valve. This
      collagenous fibers were covered by atrial and ventricular endocardium. The
      collagenous fibers of the leaflets were continuous, by their base, into the
      fibrous ring. It was observed, in a few cases, the presence of atrial muscle
      fibers into the anterior leaflet of the mitral, mainly in its central area.
      CONCLUSION: The leaflets of the mitral valve and its fibrous ring have a
      structural continuity suggesting that elements would act synchronously in the
      closure of the atrioventricular ostium during ventricular systole. The
      contraction of the myocardial bundles fixed in the fibrous ring contributes to
      decrease the diameter of the mitral ring.

PMID- 9595717
TI  - [Sublingual isosorbide-5 mononitrate during coronary arteriography. Comparison
      with sublingual nitroglycerin].
AB  - PURPOSE: To evaluate the effect of sublingual isosorbide-5 mononitrate (ISMN) and
      nitroglycerin (NTG) on luminal diameter of epicardial coronary arteries, mean
      arterial pressure and deleterious effects. METHODS: Fifty patients were submitted
      to cardiac catheterization and coronary arteriography, at baseline, and 5 min
      after sublingual administration of ISMN, group A (GA) or NTG, group B (GB).
      RESULTS: Reference vessel diameter increased in both groups, without statistical
      significance. In GA and GB, a decrease (1.66 mmHg) and an increase (0.79 mmHg) in
      mean arterial pressure, respectively, were demonstrated (p = 0.123). There were
      no deleterious effects with the use of these drugs. CONCLUSION: Sublingual ISMN
      is an alternative to administration of NTG during coronary arteriography, and
      represents a therapeutic alternative to ischemic heart disease treatment.

PMID- 9595718
TI  - [Nuclear magnetic resonance imaging in the diagnosis of left ventricular
      pseudoaneurysm. An old problem, a new option].
AB  - We describe the case of a 61 year-old female patient admitted to the hospital
      with acute lateral myocardial infarction, in pulmonary edema, who evolved to
      cardiogenic shock in the first hours. Transesophageal echodoppler-cardiogram and
      nuclear magnetic resonance imaging showed the diagnosis of a left ventricular
      pseudoaneurysm. Surgical repair was successfully undertaken.

PMID- 9595719
TI  - [Inotropic agents. Should they not be prescribed?].

PMID- 9595720
TI  - [Anatomoclinical correlation (case 6/97--Instituto do Coracao do Hospital das
      Clinicas-FMUSP)].

PMID- 9595722
TI  - [I National Consensus of Cardiovascular Rehabilitation].

PMID- 9595721
TI  - [Clinical application of intracoronary ultrasound].

PMID- 9595724
TI  - [The dura mater cardiac bioprosthesis].

PMID- 9595723
TI  - [A macromolecule capable of modifying CK-MB results].

PMID- 9595725
TI  - [Arterial dysfunction as a possible mechanism of cardiac injury in type II
      diabetic patients. A Doppler-echocardiographic study].
AB  - PURPOSE: To evaluate the left ventricular structure and function and the arterial
      stiffness in type II diabetic patients. METHODS: Thirteen diabetic patients, men
      and women (age 55 +/- 8 years) were included in the study. None of the patients
      had any other clinical disorders. Doppler-echocardiography and non-invasive
      monitoring of arterial blood pressure were performed. All the results were
      compared to an age and sex matched control group (n = 12). RESULTS: There were no
      differences between the groups for diastolic blood pressure, dimensions of
      cardiac chambers and ventricular systolic and diastolic function indexes.
      Diabetic patients had increased left ventricular mass index (101 +/- 10 vs 80 +/-
      14 g/m2; p < 0.001) and increased arterial stiffness (0.86 +/- 0.26 vs 0.69 +/-
      0.19 mmHg/mL; p < 0.05), when compared to control group. CONCLUSION: Diabetes
      mellitus is associated to increased systemic arterial stiffness and this may
      contribute to the adverse effects of diabetes on left ventricular morphology.

PMID- 9595726
TI  - [Symptoms, complications and hemodynamic changes related to dobutamine stress
      echocardiography].
AB  - PURPOSE: This study focuses on the safety and hemodynamic effects of dobutamine
      stress echocardiography. METHODS: Seven hundred and thirty five consecutive
      patients underwent dobutamine stress echocardiography for the evaluation of
      coronary artery disease and or cardiomyopathy. Dobutamine was administered
      intravenously at incremental doses of 5, 10, 20, 30 micrograms/kg/min, at 3 min
      intervals. The maximal dose was 40 or 50 micrograms/kg/min. RESULTS: Dobutamine
      significantly (p < 0.0005) increased the heart rate (from 72 +/- 12 bpm to 117 +/
      23 bpm), systolic blood pressure (from 133 +/- 21 to 157 +/- 29 mmHg) and the
      rate-pressure product (from 9.635 +/- 2.100 to 18.400 +/- 4.050, p < 0.0001) from
      baseline to peak infusion rate, respectively. There was a significant increase in
      heart rate (p < 0.05) at each infusion step, except for the 50 micrograms/kg/min
      dose, when the heart became stable. There were no deaths myocardial infarctions,
      or episodes of sustained ventricular tachycardia. Common non cardiac side effects
      included nausea, anxiety, headache, tremors and urgency in 55 (7.4%) of the
      patients. Angina pectoris occurred in 10 (1.4%) of the patients. The most common
      arrhythmias were usually mild. CONCLUSION: Dobutamine stress echocardiography is
      safe, and well tolerated. In this study complications such as myocardial
      infarction, death, ventricular tachycardia or fibrillation did not occur. There
      was no additional increase in heart rate with doses greater than 40
      micrograms/kg/min. The advantage of stress echocardiography protocol with peak
      doses of 50 micrograms/kg/min is questionable.

PMID- 9595727
TI  - [Drug treatment for stable coronary artery disease at primary and tertiary
      medical centers].
AB  - PURPOSE: To observe the distribution of the main drugs used in patients with
      stable coronary heart disease, in primary and tertiary medical care centers
      (MCC). METHODS: We studied 300 consecutive out patients at the Hetat Institute
      with the diagnosis of stable coronary artery disease, 205 (68%) males and 95
      (32%) female, aged from 31 to 80 (mean 58 +/- 8.0) years old. Drug intake was
      evaluated. RESULTS: We observed that the use of nitrates (48% vs 55%; p = NS) and
      calcium antagonists (46% vs 37%; p = NS), respectively in both primary and
      tertiary MCC was similar. The beta blockers were used more often in the primary
      MCC (50% vs 35%; p = 0.02). Angiotensin converting enzyme inhibitors (11% vs 42%;
      p < 0.001), diuretics (30% vs 49%; p = 0.002) and aspirin (44% vs 76%; p =
      0.0001) were more frequently used in the tertiary MCC. CONCLUSION: We observed
      similar frequency of use of nitrates and calcium antagonists in both centers.
      There was a higher use of beta blockers in primary MCC. The angiotensin
      converting enzyme inhibitors and antiplatelet agents were more used in the
      tertiary MCC. In relation to the updated literature, the best pharmacotherapy to
      coronary artery disease should be optimized in both centers.

PMID- 9595728
TI  - [The effects of aerobic physical training of short duration using upper limbs in
      paraplegic persons with mild hypertension].
AB  - PURPOSE: To study the modifications induced by physical training (PT) using upper
      limbs in aerobic condition of short duration on cardiovascular and metabolic
      variables. METHODS: Eleven paraplegic persons, with a mean age of 59 years, 7 men
      and 4 women with lesions at T9 through T11 and mild hypertension (HAS) were
      studied. The patients were studied before and after 12 weeks of a supervised
      program of PT, through exercise tests in a mechanic ergometer (ST) adapted for
      the arms. We employed an intermittent protocol with stress increments of 125
      (20w) and 140 kgm/min (25w) for women and men, respectively every 3 min. The
      ergometric speed ranged from 83 to 95 rpm. The oxygen consumption (VO2) was
      estimated according to American College of Sports Medicine equation for arms. The
      exercise intensity during the TF program was estimated through the Karvonen
      cardiac frequency reserve, with a variation of 65% to 85% and the Borg stress
      scale of subjective perception during the stress test. RESULTS: The mean maximal
      aerobic capacity increased in 22% (930 +/- 349 vs 1138 +/- 290 mL/min; p =
      0.003); there was a reduction of systolic and diastolic pressures at rest and
      after submaximal exercise of 4%, 15% and 5% and 5%, respectively. CONCLUSION:
      Physical training of mild to moderate intensity using the upper limbs in
      paraplegic persons, besides inducing functional capacity increment, is an
      important model of non drug control of the hypertensive response.

PMID- 9595729
TI  - [Early luminal diameter reduction after coronary angioplasty and its relation to
      the restenosis phenomenon].
AB  - PURPOSE: To evaluate the early luminal diameter loss in the first 15 min after
      percutaneous transluminal coronary angioplasty (PTCA) and its influence on
      coronary restenosis. METHODS: In a prospective study, we evaluated 86 patients.
      The patients were divided in two groups based on the presence or absence of
      coronary restenosis. Thirty one lesions developed restenosis and 55 lesions did
      not. RESULTS: Univariate analysis showed that balloon/artery ratio was lower in
      the group of restenosis (0.92 +/- 0.01 vs 1.00 +/- 0.11, P = .003). Absolute and
      relative elastic recoil at 1 min was greater in the group that developed
      restenosis (0.79 +/- 0.54 vs 0.68 +/- 0.59 mm; P = .007 and 32.04 +/- 14.27 vs
      22.15 +/- 16.65%; P = .006). Similarly, absolute and relative elastic recoil at
      15 min were greater in the group with restenosis (1.25 +/- 0.59 vs 0.90 +/- 0.65
      mm, P = .017 e 46.75 +/- 15.69 vs 29.18 +/- 17.84%, P < .00001). Minimal luminal
      diameter (MLD) at 1 min was lower in the group with restenosis (2.15 +/- 0.42 vs
      2.43 +/- 0.58 mm; P = .022). The very early loss was greater in the group with
      restenosis (0.46 +/- 0.34 vs 0.22 +/- 0.35 mm, P = .004). MLD at 15 min was lower
      in the group of restenosis than in the group without restenosis (1.69 +/- 0.48 vs
      2.20 +/- 0.61; P = .0001). Multivariate analysis revealed balloon/artery ratio
      and MLD at 15 min as independent correlates of the late outcome. CONCLUSION: The
      late outcome of PTCA is influenced by elastic recoil and the early MLD loss after
      PTCA. However, the strongest and most important predictors of late outcome by
      multivariate analysis were balloon/artery ratio and MLD at 15 min.

PMID- 9595730
TI  - [Intermittent myocardial ischemia after surgical angioplasty of left main
      coronary artery].
AB  - Two 38 and 53-year old male patients with unstable angina, whose hemodynamic
      study showed an isolated stenosis of the left coronary artery ostium, were
      submitted to a surgical angioplasty of the left main coronary artery (LMCA) with
      saphenous vein patch. At the end of the operation, the patients presented
      intermitent myocardial isquemia. One of them led to abrupt cardiogenic shock
      which reversed completely. The postoperative hemodynamic study demonstrated
      excellent left main coronary artery patency and normal left ventricular of LMCA
      has been proposed as an alternative technique to the treatment of ostial lesions,
      the surgical team should be prepared to face severe operative morbidity. The LMCA
      spasm has been considered as a possible etiology of that event.

PMID- 9595731
TI  - [Thrombosis in normal coronary arteries causing acute myocardial infarction in an
      alcoholic patient].
AB  - A case of a young patient, heavy drinker, who suffered an acute myocardial
      infarction (AMI), and whose cinecoronariography, early post unsuccessful
      intravenous thrombolysis, showed the presence of thrombi in multiple arteries is
      reported. A second cinecoronariography performed on the 7th day post AMI revealed
      normal coronary arteries. There were no plasmatic lipid or coagulation
      abnormalities, nor other risk factors for coronary artery disease. We speculate
      about the role of the heavy alcohol ingestion in this particular case.

PMID- 9595732
TI  - [Upper limbs ergometry. An important method in the assessment of
      cardiocirculatory response to exercise].

PMID- 9595733
TI  - [Fetal echocardiography. Presentation of a method].

PMID- 9595734
TI  - [Fetal echocardiography. New frontiers].

PMID- 9595735
TI  - [Fetal circulation physiology and diagnosis of functional alterations of the
      fetal heart].

PMID- 9595736
TI  - [Fetal cardiac malformations. Diagnosis and management].

PMID- 9595737
TI  - [Fetal arrhythmias].

PMID- 9595738
TI  - [New seas].

PMID- 9595739
TI  - [Computer-assisted image processing for quantifying histopathologic variables in
      the healing of colonic anastomosis in dogs].
AB  - BACKGROUND: The authors present the experimental results of the computerized
      quantifying of tissular structures involved in the reparative process of colonic
      anastomosis performed by manual suture and biofragmentable ring. The quantified
      variables in this study were: oedema fluid, myofiber tissue, blood vessel and
      cellular nuclei. MATERIAL AND METHODS: An image processing software developed at
      Laboratorio de Informatica Dedicado a Odontologia (LIDO) was utilized to
      quantifying the pathognomonic alterations in the inflammatory process in colonic
      anastomosis performed in 14 dogs. The results were compared to those obtained
      through traditional way diagnosis by two pathologists in view of counterproof
      measures. The criteria for these diagnoses were defined in levels represented by
      absent, light, moderate and intensive which were compared to analysis performed
      by the computer. RESULTS: There was significant statistical difference between
      two techniques: the biofragmentable ring technique exhibited low oedema fluid,
      organized myofiber tissue and higher number of alongated cellular nuclei in
      relation to manual suture technique. CONCLUSION: The analysis of histometric
      variables through computational image processing was considered efficient and
      powerful to quantify the main tissular inflammatory and reparative changing.

PMID- 9595741
TI  - [Medical graduation and specialization: an apparent incompatibility].
AB  - PURPOSE: Partial results of a continuous evaluation process of the undergraduate
      medical course at Escola Paulista de Medicina (EPM) started in 1989 are
      presented. METHODS: A survey on expectations and opinions about the medical
      course of EPM was carried out among faculty members, students and alumni.
      RESULTS: The authors call into question that the medical formation is non
      terminal as indicated by the late entry to labor market. CONCLUSION: The authors
      consider that the phenomenon is not related to quality aspects but to the
      specialization process started during the medical course and completed only with
      graduated studies.

PMID- 9595740
TI  - [Severe acute diarrhea associated to classic enteropathogenic Escherichia coli
      (EPEC): clinical features and fecal losses in hospitalized infants].
AB  - Enteropathogenic Escherichia coli (EPEC) strains are the most prevalent
      enteropathogenic agents isolated in the stools of hospitalized infants with
      severe acute diarrhea in Sao Paulo. These microorganisms induce a severe
      intestinal secretion of fluids and electrolytes that can cause dehydration
      leading to hospital admission in the majority of the cases. OBJECTIVES: This
      investigation aims at the following objectives: 1) to study the clinical features
      of acute diarrhea in male infants who were hospitalized owing to EPEC infection;
      2) to determine the fecal fluid losses, formula intake and variation of the body
      weight during the evolution of the disease. PATIENTS AND METHODS: Thirty eight
      male infants with acute diarrhea due to EPEC strains were studied. The clinical
      and epidemiological features of the patients were recorded and the different EPEC
      serogroups were identified. The infants were kept in a metabolic bed in order to
      allow the collection of stools and urine separately during the whole period of
      the disease, and daily metabolic balances were also obtained. The mean duration
      of the metabolic study was 5.8 days, and during this period of time 220 daily
      metabolic balances were accumulated and analyzed. RESULTS: The main clinical
      features of the studied group were as follows: age below 12 months; low birth
      weight; precocious weaning; severe protein-calorie malnutrition. EPEC 0111 was
      the most frequent serogroup identified, present in 68.4% of the infants. The
      average daily fecal fluid losses were 66 ml/kg and the mean daily formula intake
      was 85.2 ml/kg. Cow's milk was the most precocious food utilized and the infants
      who received cow's milk feeding presented the largest stool losses in comparison
      with lactose free formulas and total parenteral nutrition. CONCLUSION: EPEC
      strains are able to induce moderate to severe fecal fluid losses in infants and
      the duration of diarrhea is usually below 15 days, although in several
      circumstances diarrhea can show a protracted evolution owing to food intolerance
      associated or not with intestinal secretion.

PMID- 9595742
TI  - [Proposition of an anatomic and functional reserve into the spinal canal, as an
      interference factor on the mechanical degenerative low back pain and sciatica
      physiopathology].
AB  - OBJECTIVE: To test the hypothesis of an anatomic and functional reserve in the
      spinal canal that explains the radiological changes in lumbar spine of
      asymptomatic individuals, the differences in modalities of clinical presentation
      and the discrepancies in the prevalence of mechanical and degenerative low back
      pain and sciaticas. CASES AND METHODS: Two groups of 27 persons were submitted to
      computed axial tomography. In one group, the patients presented low back pain
      and/or sciaticas. The other formed by matched controls, showed no signs or
      symptoms. The bony canal area, dural sac area, interfacets distance and lateral
      recesses depth were quantitative assessed. RESULTS: The asymptomatics ones had
      larger bony canals than the acute and chronic patients, due to statistical
      significant differences. The ranges responsible for these differences and whose
      averages had higher figures in the asymptomatics ones in relation to the chronic
      patients, were the bony canal areas at L3-L4, L4-L5, the dural sac area and
      lateral recesses depth at L4-L5; in relation to acute ones: the bony canal areas
      at L3-L4, L4-L5, L5-S1, dural sac area at L4-L5, L5-S1, and sagittal diameter L5
      S1 and lateral recesses depth at L4-L5. CONCLUSIONS: The radiological changes in
      asymptomatic ones, the lack of symptoms in the control group, the presence of
      chronic and acute features and the discrepancies in the prevalence of low back
      pain were attributed to the existence of an anatomic and functional reserve. This
      reserve would be determined by the presence of a "safety factor" which would have
      differential distribution in asymptomatics, acute and chronic. It would be the
      element able to influence the presence or absence of low back pain in persons
      with radiological changes.

PMID- 9595743
TI  - [Low complement levels in urticarial vasculitis as first manifestation of
      systemic lupus erythematosus].
AB  - Hypocomplementaemic urticarial vasculitis syndrome is a leukocytoclastic
      vasculitis characterized by urticarial lesions, associated with fever,
      arthralgias, arthritis and abdominal pain. Other systemic manifestations include
      glomerulonephritis, uveitis, episcleritis, chronic obstructive pulmonary disease
      and neurological abnormalities. Some case associated with systemic lupus
      erythematosus have been described and SLE diagnosis was made by previous or
      concomitant diagnostic criteria before onset of urticarial vasculitis. Urticarial
      vasculitis prior to SLE diagnosis is rare. The development of anti-Ro/SS-A
      antibody for the diagnosis of SLE is emphasized. The authors alert to the
      importance of periodically searching for this marker in patients with urticarial
      vasculitis.

PMID- 9595744
TI  - [Infection in hospitalized diabetics].
AB  - BACKGROUND: To analyse the infectious diseases of inpatient diabetics in a
      general hospital. MATERIAL AND METHODS: We selected retrospectively 233 records
      of diabetics admitted during September, October and November 1990. There were 38
      (16.3%) patients with infection, age 58.9 +/- 15.3 years, 29 (76.3%) were female,
      duration of diabetes were 10.8 +/- 9.1 years and 86.3% (n = 33) were possibly DM
      type II. RESULTS: Peripheral macrovascular disease was the main cause of
      admission (42%). Forty infectious processes were analysed (two patients had two
      sites of infection). Cultures were performed in 77.5% of the cases and no
      microorganism predominated, even when different sites of infection were analysed.
      Urinary tract infection were the most frequent one (55%, n = 22), and 86.4% (n =
      19) of them were observed in female. Pulmonary infections accounted for 71.4% of
      the cases of sepsis which occurred in 18.4% (n = 7) of our population. All
      patients with sepsis died. CONCLUSION: Considering infections a worsening factor
      for diabetic patients we could conclude that it is important to perform some
      prophylatic measures to avoid them.

PMID- 9595745
TI  - [Colorectal lipomas: anatomoclinical study of 29 cases].
AB  - OBJECT: To evaluate the incidence of colorectal lipomas, its diagnostic
      methodology and therapeutic management. CASUISTIC AND METHODS: The reviewed
      necropsies performed in a six years period and the patients' records from
      colorectal lipomas cases treated up to 1965 until 1993 were studied enhancing the
      clinical presentation, their diagnosis and therapy. The 29 cases of submucosal
      intestinal lipomas were disposed in three groups. The first group with ten
      patients lipomas were detected at necropsies. The second group with 11
      symptomatic patients and group three with 8 asymptomatic patients which lipomas
      were discovered accidentally in surgical specimens resected due to neoplasm or in
      the course of diagnostical procedure. RESULTS: 0.56% of patients who were
      submitted to necropsy disclosed colorectal lipomas situated preferentially in
      right colon and in female. Enterourhage was the most often symptom (54.5%) in the
      group two, followed by cramp abdominal pain. Intussusception appeared in three
      patients (27.3%). Contrary to the medical literature, the symptomatic lipomas
      were preferentially situated in left colon and its mean size was 6.1 cm. The
      diagnosis were performed through opaque enema and more recently by colofibroscopy
      and CT scan. Resections were performed in all patients: five were enlarged, three
      were local and other three were endoscopic resections. Multiple lipomas were
      detected in 30% of patients who were submitted to necropsy and in 25% of
      asymptomatic group. In both groups no tumor was larger than 2.0 cm of diameter.
      CONCLUSIONS: Colorectal lipomas are rare in both clinical presentation and
      necropsy. Before the advent of CT scan and colofibroscopy the majority of the
      patients were submitted to wide resections, in the assumption of malignancy.
      Afterwards the endoscopic polipectomy and local resection became our preferential
      management.

PMID- 9595746
TI  - [Bacteremia after endoscopic retrograde cholangiopancreatography with and without
      therapeutic procedure: frequency, associated factors and clinical significance].
AB  - PURPOSE: To determine the frequency, associate factors and clinical features of
      bacteremia in patients undergoing endoscopic retrograde cholangiopancreatography
      (ERCP), with or without therapeutic procedures. METHODS: Prospectively, 42
      consecutives patients undergoing 46 endoscopic retrograde
      cholangiopancreatographies (ERCPs) from August to December 1994 were analyzed.
      The search for bacteremia was done by drawing 6 blood samples for cultures from
      peripheral blood. Two blood samples were collected before the ERCP and 4 of them
      after. The bottles used for cultures were Bactec bottles. The bottles were
      incubated in the Bactec 9240 system, and eventual bacteria detect were
      identificated by the manual routine of the laboratory and also with the
      autoScan/Microscan system. RESULTS: All blood cultures obtained before the ERCPs
      were negatives. Bacteremia were detected after 7 endoscopic procedures. In two
      episodes of bacteremia, the microorganism identified (Staphylococcus epidermidis)
      was considered to be a contaminant. The other 5 episodes of bacteremia were
      considered true bacteremia (frequency- 10.9%), and the microorganisms identified
      were: Streptococcus viridans, Corynebacterium sp., Enterobacter cloacae,
      Klebsiello oxytoca and Enterobacter aerogenes. This episodes were more frequent
      in the blood cultures obtained immediately after the ERCPs (p < 0.05), and
      occurred exclusively in the patients who were not receiving antibiotics (p =
      0.0192). Clinical manifestation of the episodes of bacteremia were not detected.
      CONCLUSION: The episodes of bacteremia occurred exclusively in the patients who
      were not receiving antibiotics, were transient and completely no symptomatic.

PMID- 9595747
TI  - [Neoplasms associated with esophageal epidermoid carcinoma].
AB  - INTRODUCTION: The esophageal epidermoid cancer has an important association with
      aerodigestive tract neoplasms and possibly share the same risk factors.
      Furthermore, other neoplasms can be associated with esophagus cancer. OBJECTIVE:
      To analyze retrospectively the patients with esophageal epidermoid cancer (EEC)
      and associated neoplasms, treated by the Esophagus Stomach and Small Intestine
      Group of Surgery at Hospital de Clinicas de Porto Alegre from January 1988 to
      June 1995. PATIENTS AND METHODS: Nineteen (7.28%) of the 261 studied patients had
      associated neoplasms to the EEC. Ten patients presented synchronic tumours and 9
      metachronic ones. The predominant sex was the masculine with 17 cases. The mean
      age was 62.52 years in the moment of the esophageal cancer diagnostic. RESULTS:
      The aerodigestive tumours, squamous carcinomas in totality, represented the
      predominant associated neoplasm histological type in 68.42% of the cases. The
      most frequent associated aerodigestive tumours site was the respiratory tract
      (53.8%), followed by the oral cavity and oropharynx (23%) and larynx (23%). In
      our sample, twelve patients were smokers and 9 were alcohol abusers. In relation
      to the EEC treatment, surgery was performed in 6 patients. The associated
      neoplasm was treated with radical surgery in 11 patients and radiotherapy in 5.
      Surprisingly 4 cases (21%) of gastric adenocarcinoma associated to the EEC were
      diagnosed, treated with radical surgery in 3 patients. CONCLUSION: The authors
      call attention to the importance of a criterial staging as well as the follow up
      in patients with EEC owing to the significant association with others neoplasms,
      principally with aerodigestive tumours, and discuss the common risk factors
      possibility: tobacco and alcohol use. Important association with gastric
      neoplasms were found in this casuistry.

PMID- 9595749
TI  - [Hibernating myocardium: a clinical reality].
AB  - Myocardial hibernation is believed to occur in ventricular dyssynergic regions
      chronically deprived of coronary flow enough to warrant the preservation of
      contractile function. Pathophysiology of this condition remains largely unclear,
      mainly because good experimental models for its study are still lacking. Various
      methods can be clinically employed to detect hibernation in patients with chronic
      ventricular dysfunction. These methods use the principle of unmasking contractile
      reserve, or are based on the demonstration of preserved membrane function or
      myocardium metabolism in the dyssynergic regions. The correct identification of
      viable hibernating myocardium is crucial in the process of deciding which
      coronary disease patients would potentially benefit from revascularization
      procedures.

PMID- 9595748
TI  - [Surgical treatment of acquired palpebral ptosis (lymphocytoma cutis)].
AB  - A clinical case of acquired palpebral ptosis caused by a rare pathology,
      lymphocytoma cutis, is reported. An eyelid ptosis was characterized with the
      patient unable to lift the eyelid. The resection of the eyelid nodules was
      performed using blefaroplasty incision as access and the result of the
      anatomopathological examination confirmed the diagnosis: lymphocytoma cutis. The
      surgical result was satisfactory not only esthetically but also functionally (2
      year follow-up).

PMID- 9595751
TI  - [Videolaparoscopic access in the surgical treatment of colorectal cancer:
      critical analysis].

PMID- 9595750
TI  - [Similia Similibus Curentur: historical background of homeopathic medicine].
AB  - The history of homeopathic medicine was focused on the present work since the
      first ideas historically described by Hypocrates, Galeno, Paracelsus and
      Hahnemann. We intended to give an idea of the evolution of medical sciences in
      general, including the gradual arise of ideas which led Hahnemann to create
      homeopathy.

PMID- 9595752
TI  - [Restenosis after coronary balloon angioplasty: the clinical problem].

PMID- 9595753
TI  - [Peptides derived from collagen: new biochemical markers of bone metabolism].

PMID- 9595754
TI  - [Clinical assessment of risk factors to restenosis post coronary angioplasty].

PMID- 9595755
TI  - [Accidents and acts of violence in Brazil: I--Analysis of mortality data].
AB  - External causes are an important cause of death in almost all countries. They are
      always the second or third in the mortality ranking, but their distribution
      according to type varies from country to country. Mortality due to external
      causes by type, gender and age, for Brazil as a whole and for state capitals
      specifically, is analysed. Mortality rates and the proportional mortality from
      1977 to 1994 were calculated. The results showed that the number of deaths due to
      external causes has almost doubled from 1977 to 1994 and nowadays this is the
      second cause of death in Brazil. The mortality rate, in 1991, was 69.8 per
      100,000 inhabitants and the highest increase was in the male rates. The male
      rates are almost 4.5 times greater than the female ones. The first cause of death
      among people from 5 to 39 years old is external causes, and the majority occur
      between 15 and 19 years of age (65% of the deaths by external causes). Besides
      the growth in itself it also seems that a shift of deaths to hower ages is
      occurring. Both mortality by traffic accidents and that by homicide have
      increased over the period from 1977 to 1994. Suicides have been stable and "other
      external causes" have increased slowly, especially due to falls and drowning. The
      mortality rates for external causes in state capitals are higher than the average
      for Brazil as a whole, except for some northeastern capitals. The rates for the
      capitals in the northern region are the highest in Brazil. In the northeastern
      region, only Recife, Maceio and Salvador have high rates. In the southeast,
      Vitoria, Rio de Janeiro and S. Paulo have the highest rates in the country but
      Belo Horizonte's rates are declining. In the southern region all the capitals
      showed a growth in the rates as also in the capitals of the West-central region.
      The growth of mortality due to external causes type of external cause is
      different in these capitals. Suicide is not a public health problem in Brazil nor
      the state capitals. Traffic accidents are a major problem in Vitoria, Goiania,
      Macapa, the Distrito Federal and Curitiba. Homicides have increased greatly in
      Porto Velho, Rio Branco, Recife, S. Luis, Vitoria, S. Paulo, Curitiba, Porto
      Alegre, Cuiaba and the Distrito Federal. The mortality due to external causes in
      Brazil has become a major public health problem, especially because of homicides.
      It is important to emphasize that the quality of the mortality data on external
      causes is not the same for all capitals, because it is a question very closely
      related to the quality of legal information.

PMID- 9595757
TI  - [Accidents and acts of violence in Brazil: III--Economic impact of external
      causes in Brazil: an attempt at measurement].
AB  - The study seeks to make a first estimate of the economic impact of lesions and
      poisonings in Brazil, measured in terms of hospital expenses on internments--in
      days of general permanence and in Intensive Care Units. Internments is hospital
      under contracts with the United Health System are analysed by means of the AIH--
      Authorization for Hospital Internment. These internments involve expenses per
      annum corresponding to approximately 0.07% of the GNP of the country. With regard
      to mortality, the economic impact has been analysed by the use of the Potential
      Years of Life Lost indicator. It may be verified that accidents and acts of
      violence represented about 2.6 million years of life lost in 1981, and 3.4
      millions in 1991. The increase was thus of about 30%, even though for the total
      of data deaths showed a reduction. Despite some limitations, it is possible to
      estimate the general magnitude of the economic impact of external causes of
      death. It is hoped that these limitations may serve as a stimulus to new and
      deeper investigations.

PMID- 9595756
TI  - [Accidents and acts of violence in Brazil: II--Hospital morbidity from lesions
      and poisonings].
AB  - Today in Brazil the "Hospital Internment Authorizations" (AIH) represents about
      80% of the total internments in the country and constitutes a data base of easy
      access available in CD-ROM. This high coverage allows one to draw a reasonable
      picture, close to reality, of the morbidity demanding hospitalization. Among the
      causes there is the diagnostic category lesions and poisonings noteworthy for
      severity and frequency. Hospital internments by this diagnostic category
      occurring in a month in 1994 have been focused on. Some epidemiological and
      hospital use characteristics, such as demographic aspects, specific diagnostic
      category, length of stay and mortality are described. It was observed that
      lesions and poisonings accounted for 5% to 6% of all hospital internments in the
      country, being predominantly among men under 65 of age. This diagnostic category
      was the first cause of hospital internments among men of from 15 to 29 years of
      age. Fractures were the most frequent specific diagnosis (about 37.5%), almost
      all of them involving members (legs or arms). The injuries were mainly located in
      hands, arms, head and neck and occurred predominantly among young men, leading to
      the believe that they were due to work or traffic accidents. Regarding burns, the
      fragment occurrence among children under 5 years of age is worthy of note. The
      authors lament the lack of information as to their causes such as would enable
      appropriate preventive actions to be taken.

PMID- 9595758
TI  - [Accidents and acts of violence in Brazil: IV--Report of an experiment related to
      traffic accident prevention: a model used by the Pan American Health
      Organization].
AB  - The report of a program related to the prevention of traffic accidents in Bogota,
      Columbia, in 1983, is presented. The methodology applied showed that ostensive
      and preventive policing produced immediate results and its adoption was
      relatively simple: the number of accidents declined from 414 to 48 within on year
      of the launching of the Program.

PMID- 9595759
TI  - [Accidents and acts of violence in Brazil: conclusion].

PMID- 9595760
TI  - [Accidents and acts of violence in Brazil: accidents and acts of violence/lesions
      and poisonings and the 10th revision of the International Classification of
      Diseases].

PMID- 9595761
TI  - [Tuberculosis associated with AIDS: the situation in a Northeastern region of
      Brazil].
AB  - INTRODUCTION: The main aspects of the HIV and Mycobacterium tuberculosis
      coinfection in the adult patients attended by the main reference hospital for
      infectious diseases in the State of Ceara, Brazil, responsible for the
      notification of 89.3% of the cases registered in the state between 1986 and 1992
      were investigated. METHODOLOGY: Data were collected from the case histories of
      patients of more than 15 years of age with a diagnosis of AIDS, attended in a
      state reference hospital in Northeastern Brazil. The analysis of the data obeys
      the criteria of the Ministry of Health for the definition of this disease.
      RESULTS: Tuberculosis had been present in 30.6% of the patients studied (151/493)
      and it was diagnosed by the first year after the AIDS diagnosis in 76.8% of the
      cases. The proportion of AIDS cases with tuberculosis is significantly greater (p
      = 0.032) among men (94.7%) than among women (88.3%). An increased linear trend in
      the proportion of cases with tuberculosis was noticed in the AIDS cases according
      to the decrease in level of schooling (p < 0.001). The direct baciloscopy of the
      sputum although considered a high priority exam, was made in only 72.9% of the
      patients, presenting positive results in 28.3% of these. The extrapulmonary form
      was detected in 23.9% of the cases and, among those, the miliary form in 25% and
      the meningitis in 16.7%. These results differ in a significant way (p < 0.001 for
      all) from the cases with tuberculosis without HIV infection in adults registered
      in the state in 1992 (9.8% extrapulmonary, 7.2% miliary and 3.3% meningitis). In
      most cases, death occurred in the presence of tuberculosis (52.3%), and only
      10.6% managed to recover from the tuberculosis. CONCLUSIONS: The premature
      development of tuberculosis in AIDS patients, the presence of a high percentage
      of extrapulmonary forms and the high lethality are indicator that the prevention
      and control measures of these two pathologies cannot be considered separately in
      this State.

PMID- 9595762
TI  - [Infant mortality in a midwestern municipality of the State of Sao Paulo, Brazil,
      1990 to 1992].
AB  - INTRODUCTION: Infant mortality was studied in an urban area of Southeastern
      Brazil in the period from 1990 to 1992 using data from death certificates
      collected at the registry office, by the application of methods for obtaining a
      collective diagnosis which will assist in the identification and choice of
      strategies for the control of local problems. MATERIAL AND METHOD: The original
      data were corrected using documental research into health services and household
      interviews. Data of the Live Birth Information System (SINASC) was used to study
      variables such as maternal age and birthweight. The quality of original death
      certificates was initially analyzed using the amount of information, sensitivity,
      specificity and Kappa value. RESULTS: The global sensitivity for the underlying
      cause was 78.84% and Kappa 71.32% for the total of causes. One hundred and eighty
      nine deaths occurred, 66.15% of them in the neonatal period, (41.28% during the
      first day of life) and 33.85% in late childhood. The birthweight of 58.28% of
      deaths was less than 2.500 g. The underlying causes of death were studied the by
      possibility, of their avoidance (a method developed by Erica Taucher), by a
      "reduced" group of causes (utilized in International Collaborative Effort (ICE)),
      multiple causes statistics and geographical distribution. It was observed that in
      the deaths occurring up to 27 days, 22.23% could have been avoided by adequate
      care during labour, and 20.64% could have been avoided by early diagnosis and
      early treatment, 13.75% by good pregnancy care and only 7.94% were unavoidable.
      Of the deaths occurring in late childhood, 12.17% were classified as of avoidable
      causes and 4.23% were considered as unavoidable. Using ICE groups, 58.74% died of
      immaturity or asphyxia, 19.58 of infection and 12.17% from congenital
      abnormalities. CONCLUSIONS: The results suggest that priority be given to
      obstetrical care at delivery and during labour and to the pediatric care of low
      birth weight, among others. The analysis using multiple causes statistics shows
      that 76.05% of the deaths have underlying causes related to neonatal disorders
      and confirms the relationship with the weight deficiencies of the newborn. The
      maternal complications were also related to weight deficiencies. Great
      differences were identified in infant mortality rates in urban zones not only
      restricted to the value of the rates but also to the diseases responsible for the
      occurrence of deaths. We therefore conclude that there is an advantage to be
      gained in using the four methods, which are complementary, for studying or
      planning actions with a view to prevent infant mortality.

PMID- 9595763
TI  - Factors affecting nutrition behavior among middle-class adolescents in urban area
      of Northern region of Brazil.
AB  - INTRODUCTION: Brazil has been called a nation in nutrition transitional because
      of recent increases in the prevalence of obesity and related chronic diseases.
      With overweight conditions already prevalent among middle-income populations,
      there exists a need to identify factors that influence nutrition behavior within
      this group. OBJECTIVE: To address this subject, a research study was implemented
      among middle-class adolescents attending a large private secondary school in
      Manaus, Amazonas, Brazil. The study determined the availability and accessibility
      of snack foods as well as subjects' attitudes and preferences towards, and the
      influence of family and friends on healthy (high-nutrient density) snack choices.
      METHODS: The 4-stage process included: (a) a nutrition expert focus group
      discussion that reported local nutrition problems in general and factors related
      to adolescent nutrition, (b) an adolescent pilot survey (n = 63) that solicited
      information about snacking preferences and habits as well as resources for
      nutrition information and snack money: (c) a survey of various area food market
      sources to determine the availability and accessibility of high nutrient density
      snacks; and (d) a follow-up adolescent survey (n = 55) that measured snack food
      preferences and perceptions about their cost and availability. RESULTS: Results
      included the finding that, although affordable high nutrient density snacks were
      available, preferences for low nutrient density snacks prevailed. The adolescents
      were reportedly more likely to be influenced by and obtain nutrition information
      from family members than friends. CONCLUSION: From study results it is apparent
      that a focus on food availability will not automatically result in proper
      nutritional practices among adolescents. This fact and the parental influence
      detected are evidence of a need to involve adolescents and their parents in
      nutrition education campaigns to improve adolescent snack food choices.

PMID- 9595764
TI  - [Sources of information and their relationship to the degree of knowledge about
      AIDS in Mexican adolescents].
AB  - INTRODUCTION: In Mexico 2.1% of the cases of AIDS are in adolescents. The cases
      of AIDS in the age group of 20 to 29 account for 30.5% of all the cases and an
      important proportion could have been infected with HIV in their adolescence, in
      view of the length of the incubation period from the infection with HIV to the
      manifestation of the syndrome. The adolescent's knowledge of HIV/AIDS varies. In
      some urban contexts the adolescents have lay concepts and myths that could guide
      them into misting practices that could lead to contamination by HIV. The mass
      media, especially television, and interpersonal sources such as teachers, parents
      and peers are important sources of information about HIV/AIDS and have a central
      role in the social construction and public perception of the problem in
      adolescents. The objective of the study is to relate the degree of knowledge of
      HIV/AIDS to the exposure to information sources among adolescents in Guadalajara
      city, in Mexico. MATERIAL AND METHOD: Survey sample with autoapplied
      questionnaire. Sample of 1,410 adolescents, male and female, of 15 to 19 years of
      age, in the four socioeconomic strata. The Chi-square and BTukey tests, 95%
      confidence interval for proportions and means, and simple ANOVA factor were
      applied. RESULTS: A considerate degree of knowledge (mean of 13.94 correct answer
      out of 24, standard deviation = 4.09, 95% CI = 13.69-14.11) was found significant
      mean differences in favor of the high (15.70) and medium (14.26) strata as
      opposed to the low (13.51) and marginalized (12.85) (F = 19.39, p < .0001, BTukey
      level .050). The information published by the newspapers (F = 11.1; p < .001) and
      the teachers (F = 3.72; p < .05) had a direct relationship to the degree of
      knowledge imported by the daily exposure to the television and other social
      demographic variables. CONCLUSIONS: The results describe the presence of
      inequalities by socioeconomic strata in the list of sources in information and
      the levels of knowledge about HIV/AIDS. It is necessary to strengthen and develop
      educational action and the publication of messages through the media,
      institutions and interpersonal networks, with emphasis on interpersonal and media
      sources available to the low and marginalized strata, and at the same time, to
      strengthen the action of sources of information available to the other
      socioeconomic strata.

PMID- 9595765
TI  - [Use of outpatient services in an urban area of Southern Brazil: place and
      frequency].
AB  - OBJECTIVE: The objective was determine the use of health services by the adult
      population in Pelotas, RS, Brazil. METHODS: A cross-sectional study was made on
      the basis of a population sample. One thousand six hundred and fifty-seven
      persons we interviewed during the months of March and June, 1992. A percentage of
      9.7 of the sample was lost. RESULTS: Two dependents variables. One the type of
      service as determined by type of payment. The other the number of medical visits
      made during the previous year. The type of service was seen to be associated with
      the following social variables: social class, level of schooling and place of
      residence. The frequency of medical visits was associated with sex, risk factors
      and reasons for the visit. CONCLUSION: It was concluded that choice of the type
      of service depends more heavily in social class than other variables associated
      with the severity of the disease in question.

PMID- 9595766
TI  - [Mosquito (Diptera: Culicidae) ecology in natural and artificial rural breeding
      places in northern Parana, Brazil. V. Larvae collection in artificial containers
      installed in ciliary forest].
AB  - INTRODUCTION: The use of receptacles containing water for the laying of the
      Culicidae eggs in an anthropogenic area, may indicate a genetic plasticity that
      leads them evolutionarily towards domiciliation. Thus, the various species of
      Culicidae which colonize the receptables placed in reparian forest were collected
      for this study. MATERIAL AND METHODS: The materials used were: Tires, plastic,
      can and bamboo receptacles, installed in a rural area of a reparian forest along
      a river in Northern Parana, Brazil. RESULTS: The results were obtained by means
      of the collection of Cx.grup coronator, Cx. declarator, Cx. laticlasper, Cx.
      (Melanoconion), Cx. section Spissipes, Cx. mollis, Ae. terrens, Tr. compressum,
      Tr. pallidiventer, Hg. leucocelaenus, Cx. quinquefasciatus, Li. durhamii and
      Toxorhynchites sp larvae. The first five species were tire specific, while the
      two Trichoprosopon species were bamboo specific. Ae. terrens and Cx. mollis were
      collected both in tires and bamboo, Cx. bigoti was collected in tires, cans and
      bamboo, while Hg. leucocelaenus could only be found in cans. The last four
      species were collected in all kinds of receptacles. Cx. quinquefasciatus, Cx.
      eduardoi and Li. durhamii had significant population fluctuations. DISCUSSION:
      Tires were characterized as the receptacle most acceptable to the Culicidae. The
      areas where the forest was the densest and the places where the soil was the most
      humid were the spots with the highest capture register.

PMID- 9595767
TI  - [Phlebotomines (Diptera: Psychodidae) focusing visceral leishmaniasis in the
      State of Mato Grosso do Sul, Brazil].
AB  - INTRODUCTION: In the Americas, Lutzomyia longipalpis has been incriminated as the
      vector of visceral leishmaniasis in almost all the areas in which this disease
      has been reported. The notification of human cases of visceral leishmaniasis and
      the presence of dogs with an appearance suggestive of the disease in the country
      of Corumba, Mato Grosso do Sul State, Brazil, led us to undertake an
      entomological investigation in this area, for the purpose of identifying the
      phlebotomine vector. MATERIAL AND METHOD: The county of Corumba is located in the
      Pantanal region and its urban area is situated at 18 degrees 59' 44" South and 57
      degrees 39' 16" West. The research project was carried out in peri and
      intradomiciliary environments, in three urban districts, one of which was central
      and the other two on the outskirts, and in a cave situated outside the urban
      perimeter. Most of the captures were made weekly with light automatic traps, in
      the period from February 1984 to December 1986. Meteorological data for this
      period were obtained from the city's meteorological station and those for the
      period from 1925 to 1982 from the literature. RESULTS: The urban phlebotomine
      fauna consisted of eight species and was similar to that of the cave, except that
      in the latter the species were more abundant. Lutzomyia cruzi was predominant in
      the peri and intradomiciliary environments. Its prevalence in the central
      district was of 90.3% and lower in the outskirts. Lu. forattinii presented
      considerable prevalence (39.0%) in one of the outlying districts too. In the
      cave, Lu. corumbaensis was the predominant species, followed by Lu. sordellii,
      Lu. forattinii, Lu. peresi and Lu. cruzi. The impact of the climatic condition
      and the action of insecticides in the urban area on the frequency of the species,
      as well as the use of the cave as a breeding ground by the phlebotomines, in view
      of the changes in the sex rate, are commented. Data on anthropophily and captures
      of Lu. forattinii using dog bait have been added. CONCLUSION: The predominance of
      Lu. cruzi in the urban area; the great prevalence of Lu. forattinii in most of
      the outlying areas studied and the anthropophily of this latter species, as well
      as the strong affinity of these species with Lu. longipalpis, the main vector of
      visceral leishmaniais in other areas of the Americas, suggest the participation
      of both in the transmission of the disease in Corumba.

PMID- 9595768
TI  - [Tuberculosis lymphadenitis in slaughtered swine from the State of Sao Paulo,
      Brazil: microscopic histopathology and demonstration of mycobacteria].
AB  - INTRODUCTION: As the occurrence of tuberculosis lymphadenitis in swine
      constitutes a public health risk, especially in immunosuppressed individuals, the
      distribution of tuberculoid lesions and the presence of microbacteria in lymph
      nodes and hepatic and muscular tissue in swine for slaughter, in the State of S.
      Paulo, SP (Brazil), in the period from 1993 to 1994, were studied. MATERIAL E
      METHOD: Tuberculous lesions in 60 carcasses of swine, slaughtered at abattoirs
      during the period 1993-1994, were studied. When macroscopic lesions were
      observed, a representative sampling of lymph nodes, hepatic and muscular tissues
      (masseter and diaphragm) were examined using histopathological and microbacterial
      isolation techniques. RESULTS: The macroscopic lesions were found predominantly
      in mesenteric lymph nodes. The MAI Complex (M.avium-intracellulare) was isolated
      mainly in the carcass group that showed lesions and was not found in the control
      group. Microorganisms of the MAI Complex were not isolated from hepatic and
      muscular tissues. CONCLUSION: No clear relationship between the type of
      mycobacteria isolated and the macroscopic lesions observed during the carcass
      inspection was found.

PMID- 9595769
TI  - [Hearing findings in subjects after meningitis].
AB  - INTRODUCTION: It was proposed to ascertain the occurrence of individuals who
      present hearing loss, due to contracting meningitis, as well as to characterize
      the diagnosed loss as far as the type, degree and the audiometric configuration
      are concerned. MATERIAL AND METHOD: The methodology used comprised a survey of
      949 references of patients attended at the Hearing Disturbance Center of the
      HPRLLP/USP, in order to select those who presented hearing loss after meningitis
      and, from the analysis of the hearing evaluation to which they were submitted,
      achieve the proposed goal. RESULTS AND CONCLUSION: The results indicated a 6.2
      percent occurrence as regards hearing loss due to meningitis in relation to other
      causes and the characteristic of this hearing loss was predominantly
      sensorineural, symmetrical, al linear and to a profound degree.

PMID- 9595770
TI  - [Immunologic behavior of meningococcal vaccines].
AB  - Meningococcal disease continues to be a great health problem on all continents
      and the meningococcal vaccines have been proposed for their prevention and
      epidemic control. The polysaccharide A and C vaccines are relatively efficacious
      with distinct immunological behavior with regard to the different age groups,
      however, up to the present no highly efficacious vaccine for meningococcal B
      disease exists. The meningococcal B capsular polysaccharide is not immunogenic
      due to the structural mimicry of mammalian tissues and efforts to produce carrier
      proteins have been proposed in order to obtain an immunogenic vaccine for all age
      groups that would if possible, protect against all the meningococci. This review
      of the literature presents the study of the development of the immunological
      behavior of all the meningococcal vaccines undergoing development and reports on
      the efforts to obtain a safe and efficacious product for the control of
      meningococcal disease.

PMID- 9595771
TI  - [Aflatoxins: current concepts on mechanisms of toxicity and their involvement in
      the etiology of hepatocellular carcinoma].
AB  - Current concepts derived from intensive research over the last decade, on
      biotransformation, mechanisms of toxicity and evidences for the involvement of
      aflatoxins in the etiology of human liver cancer are summarily presented.
      Aflatoxin B1(AFB1), the main metabolite produced by moulds of genus Aspergillus,
      exerts its effects after conversion to the reactive compound AFB1-epoxide, by the
      action of cytochrome P450-dependent enzymes. This epoxide can form derivatives
      with cellular macromolecules, including proteins, RNA and DNA. The reaction with
      DNA occurs with guanines in the codon 249 of tumor suppressor gene p53. Primary
      biotransformation of AFB1 also produces hydroxylated and less toxic derivatives,
      such as aflatoxins Q1 and P1. Differences intra and interspecies in the pathways
      of activation/detoxification are directly related to the susceptibility of
      animals to aflatoxin effects. In humans, studies of individual biomonitoring of
      AFB1 metabolites such as AFB1-N7-guanine have demonstrated that aflatoxins
      constitute an important risk factor for hepatocellular carcinoma (HCC) in exposed
      populations. Some of these studies also show a synergistic action between
      aflatoxins and the hepatitis B virus in the development of human HCC. In view of
      these concepts, and taking into account the frequent detection of aflatoxins in
      Brazilian foodstuffs, the need for investigation into the level of exposure to
      these toxins and its impact on human health is stressed.

PMID- 9595772
TI  - [Research on social support in health: current status and new challenges].
AB  - On the borderline between sociology and psychology, the concept of social support
      has made it possible to develop a whole research tradition aimed at explaining
      some of the differences existing in the distribution of mental and physical
      disease. The concept of social support itself, however, still presents some
      ambiguities which must be clarified. These problems are discussed and it is
      showed and shows that the topic can be enriched with the contribution of the
      social sciences. Different definitions of the concept itself, are briefly
      analysed and the complexity and multidimensional character of social support are
      highlighted. The association between social support and health is discussed. The
      differences and implications of the direct effect model and the buffering effect
      model are addressed, and the relevance of the construct of social support is
      enhanced. The need to study social support not only as a likely determinant of
      some forms of disease, but also as a dependent variable, is brought out. Some
      recent developments in the study of factors associated with the availability of
      social support are discussed. It is shown that social support is a product of
      certain social factors which can be clearly identified by sociological analysis.
      In order to illustrate this point, the structural determinants of a specific
      dimension of social support-attention-are discussed. The importance of structural
      variables like social class and gender in attempting to explain the differential
      distribution of certain forms of social support is emphasized. It is proposed, on
      the theoretical level, that the intersection between two related autonomous
      constructs-social class and social support-may better explain those aspects of
      these concepts that are of importance to observed heterogeneity in the
      distribution of mental and physical health. Different theoretical and
      methodological approaches to the understanding of the determinants of social
      support and its effect on health are suggested.

PMID- 9595773
TI  - [Characteristics of people involved in accidents with two-wheel vehicles].

PMID- 9595774
TI  - [Blood lead levels in the urban population].

PMID- 9595775
TI  - An alert to organ transplant centers.

PMID- 9595776
TI  - [Effect of glucidic and fat total parenteral nutrition on macrophage phagocytosis
      in rats].
AB  - Fat lipid emulsions in Total Parenteral Nutrition (TPN) have been associated to
      Mononuclear Phagocytary System (MPS) changes. Intravenous lipid emulsions may
      alter macrophage membrane composition but there are controversies about their
      effects on MPS function. The aim of the present investigation was to assess the
      influence of fat free TPN and fat emulsions TPN on the macrophage phagocytosis.
      Wistar rats (70) with external jugular vein canulation were divided in seven
      groups. The rats received, intravenously (i.v.) different isocaloric (1.16
      kcal/mL), isonitrogenous (1.5 g/mL), and isolipidic (30 to 32% of non-proteic
      caloric value) TPN regimens or oral diet: 1) Group OS: oral diet with i.v.
      infusion of saline; 2) Group GLU: fat-free TPN; 3) Group LCT: TPN with 10% long
      chain triglecide emulsion (TCL); 6) Group MCT: TPN with 10% lipid emulsion with
      medium chain triglycerides (TCM-50%) and TCL (50%). After 96 hours of TPN or
      saline infusion, colloidal carbon was i.v. injected at 1.0 mL/kg body weight. The
      rats were sacrificed after three hours. Liver, spleen and lung were weighted and
      studied by immunohistochemistry by the avidine-biotine method. Under light
      microscopy the total macrophage number (MT) and colloidal carbon phagocytic
      macrophages number (MF) were established. Phagocytic index was MT/MF x 100. The
      results were statistically analysed (p < 0.05). The group under oral diet (OS)
      was the only one to gain weight. There were no differences in organ weight in any
      group. There were changes in MT, MF and phagocytic index in all TPN groups. Fat
      free TPN inhibited liver, spleen and lung macrophage phagocytosis. Fat TPN with
      TCL inhibited liver and lung macrophage phagocytosis. At conclusion fat free TPN
      or with long chain tryglicerides may inhibit MPS phagocytosis. Further studies
      are necessary to estabilish the effect of TPN on other MPS function.

PMID- 9595777
TI  - [Chronic anal fissure: results of the surgical treatment of 220 patients].
AB  - Since results from non-surgical procedures designed for treatment of chronic anal
      fissure are still controversial, sphincterotomy remain as the "state of the art"
      therapy for this condition. In a retrospective basis, the authors intend to
      review results from treatment of chronic anal fissure in 220 patients who
      underwent surgical procedure between 1984 and 1995. Data from chart review
      included age, sex, location of the lesion at the canal anal, associated anorectal
      disease, delivered surgical technique and complications. Seventy per cent of the
      patients were male. Mean age was 37.1 years. Fissure was located at the posterior
      midline in 86.1%. Associated anorectal conditions occurred in 41.4%. Fissurectomy
      plus posterior sphincterotomy was the treatment of choice in 84.1%. Complications
      occurred in 5 (2.3%) cases. There were no incontinent patients. Mean follow-up
      was 2.6 years. The authors conclude that partial internal anal sphincter section
      produces excellent results in treatment of chronic anal fissure. Posterior
      sphincterotomy may persist effective and safe since continence impairment was not
      identified in the present study.

PMID- 9595778
TI  - [Biochemical glucose test x glucose strip test: results of 464 determinations in
      pre-term infants].
AB  - The preterm infant frequently requires glucose level monitorization. This paper
      compared determinations of blood glucose by two methods: glucose strip test and
      biochemistry. There was determined 464 pairs of glucose levels by both methods in
      40 preterm infants receiving glucose infusion. The hypoglycemia interval showed
      that the precision of strips was lower than the biochemical method. The same was
      found in hyperglycemia interval, but the result was a few better. Concluding, the
      authors emphasize the use of glucose strip test only for screening and the
      biochemical test for treatment.

PMID- 9595779
TI  - [Surgical treatment of lung abscesses].
AB  - The authors analysed a group of patients with lung abscesses that received
      surgical treatment, as well as the characteristics of their evolution. Seventeen
      patients with lung abscesses which underwent surgical therapy from 1984 to 1995
      were analysed. The group was composed of 12 male and 5 female. The age varied
      from 25 to 78 years (mean-50.1 years). The etiologies were: post-pneumonic,
      tuberculosis, foreign-body, empyema. Two types of surgical procedures were
      performed: pulmonary resection and transthoracic drainage. The indication of
      surgery was based on the failure of clinical treatment, massive hemoptysis,
      pleural empyema and residual cavity wider than 2 cm after 6 weeks of clinical
      treatment. The patients with poor clinical conditions were selected to
      transthoracic drainage, the less invasive procedure. Most patients had a
      satisfactory post-operative evolution (58.9%). Five patients had complications
      (29.4%) as empyema and air leak for more than three weeks and two patients died
      (11.9%). Regarding the surgical technics, the pulmonary resection (lobectomy and
      segmentectomy) showed no morbidity and mortality. The usage of external chest
      tube drainage of the abscess had a morbidity of 40% and mortality of 20%. In
      conclusion, the complicated lung abscess is still a surgical pathology and the
      best approach seems to be the resection of the pulmonary segment affected. The
      drainage has specific indication, mainly in patients with deteriorating
      condition, but this procedure has high mortality and morbidity rates.

PMID- 9595780
TI  - Microalbuminuria in essential hypertensives in treatment for hypertension.
AB  - Urinary albumin excretion (UAE) was evaluated in 26 subjects with essential
      hypertension and no diabetes (5 men, 21 women; 19 whites and 7 blacks), with
      creatinine clearance (Ccreat) > or = 75 ml/min/1.73 m2, in individualized
      treatment with various antihypertensive drugs. Clinical and laboratorial data
      were the following: mean age, 53 +/- 2 years (SEM); duration of hypertension,
      14.9 +/- 2.2 years; body mass index (BMI), 26.8 +/- 0.7; arterial blood pressure,
      142 +/- 4/89 +/- 3 mmHg; serum creatinine, 0.8 +/- 0.03 mg/dL; Ccreat, 99.3 +/-
      3.8 ml/min/1.73 m2 and UAE, 9.3 +/- 1.5 micrograms/min. No significant difference
      was found when data were evaluated for gender and race. Microalbuminuria, defined
      as UAE > 13.9 micrograms/min, was found in 19% of the hypertensives (range: 16.3
      to 28.1 micrograms/min). UAE correlated positively and significantly with
      systolic (r = 0.6309; P = 0.0005), diastolic (r = 0.4146; P = 0.0352), and mean
      blood pressure (r = 0.5000; P = 0.0093). The correlation between UAE and systolic
      pressure was stronger than with diastolic pressure. There was a positive and
      significant correlation between BMI and UAE values (r = 0.5623; P = 0.0028), and
      between BMI values with those of systolic (r = 0.5271; P = 0.0057) and mean blood
      pressure (r = 0.3930; P = 0.470). No correlation was found between UAE and age,
      duration of hypertension or Ccreat. Systolic, diastolic and mean blood pressures
      were significantly higher in microalbuminuric than in non microalbuminuric
      hypertensives. Obese hypertensives presented higher mean values of UAE, systolic,
      diastolic and mean pressures than non obese.

PMID- 9595782
TI  - [Primary psoas abscess in a child. Case report and review of the literature].
AB  - Primary psoas abscess is an uncommon disease. In children, clinical
      manifestations is often inspecific leading to diagnostic delay. The authors
      relate a primary pyogenic abscess of the psoas muscle in a 7-year-old girl with
      secondary septic arthritis of the hip. Confirmation of diagnosis was established
      by computerized tomography (CT) of the abdominal and pelvic areas. A review of
      the literature is presented about clinical manifestations, pathogenesis,
      differential diagnosis, etiology, diagnostic and therapeutic management of this
      infrequent entity.

PMID- 9595783
TI  - [Laparoscopic repair of chronic traumatic diaphragmatic hernia: case report and
      review of the literature].
AB  - The management of diaphragmatic injury would appear to be a simple matter of
      suturing the defect. However, preoperative diagnosis can be difficult and even at
      the time of surgery some diaphragmatic injuries can be overlooked if careful
      exploration in not done. Associated injuries tend to divert attention from the
      diaphragmatic injury. Laparoscopic diagnosis and repair have been described with
      successful.

PMID- 9595784
TI  - [Video laparoscopic splenectomy in a patient with splenomegaly due to hereditary
      spherocytosis: report of two cases].
AB  - We present a case report of laparoscopic splenectomy in two patients with
      congenital spherocytosis. A 23-year-old man and a 25-year-old woman with
      splenomegaly due to congenital spherocytosis underwent laparoscopic splenectomy.
      Their postoperative course was uncomplicated and they were discharged on the
      second and fourth postoperative day, respectively.

PMID- 9595781
TI  - [Brain metastases from papillary thyroid carcinoma: a case report and review of
      the literature].
AB  - Papillary carcinoma, the commonest thyroid malignancy, has a good prognosis and
      low incidence of distant metastases. Brain metastasis is extremely rare with a
      frequency of about 1% in reported series. In this paper we present the clinical
      details of one case of histologically proven brain metastasis from papillary
      thyroid cancer, first presented with neurological symptoms, initially treated
      with excisional biopsy and radiotherapy in other hospital, without clinical
      response. The patient was then referred to our service, where he underwent a
      total thyroidectomy and modified radical neck dissection, with the aim of
      posterior radioactive iodine treatment for the brain lesion. Unfortunately, he
      died of neurological complications, two months after the neck treatment. Also
      presented is a review of the literature of this unusual clinical presentation.

PMID- 9595785
TI  - [Retention of knowledge. I--Dermatology and psychiatry programs].
AB  - The authors present the results of an education investigation of knowledge
      retention. The programs of Dermatology and Psychiatry were studied, comparing the
      marks obtained in the fourth and fifth years. The examinations had the same
      content but were not identical and the fifth year's examination was applied in
      the first day of the training program. The losses of knowledge observed (average
      +/- standard error) were 20.0 +/- 2% for Dermatology and 27.0 +/- 3% for
      Psychiatry. These losses were not influenced by the time between the two
      examinations, by student's sex or race (oriental or not), or by the fact that the
      student had studied the contents of the disciplines out of the University program
      (hidden curriculum).

PMID- 9595786
TI  - [Knowledge retention. II--Orthopedics and traumatology programs].
AB  - The authors present the results of an educational investigation of knowledge
      retention concerning a Orthopedics and Traumatology program. The research was
      developed by comparing the marks obtained in the fourth and sixth years. The
      examinations had the same content but were not identical. Between the two
      examinations, the loss of knowledge was -17.5% +/- 1.0% (average +/- standard
      error) and was not influenced by the time between the two examinations.

PMID- 9595787
TI  - [Biochemical markers and methods to assess insulin resistance in normal, obese
      and hyperandrogenic women].
AB  - BACKGROUND: Euglycemic or hyperglycemic clamp and the frequently sampled i.v.
      glucose tolerance test are the most frequently used methods to assess insulin
      resistance. However, both are expensive and cumbersome. AIM: To evaluate the
      relative or discriminatory usefulness of sex hormone binding globulin (SHBG),
      dehydroepiandrosterone sulphate (DHEAS) and insulin like growth factor binding
      protein 1 (IGFBP-1) as markers of insulin resistance and to estimate the tissue
      sensitivity to insulin by means of the insulin tolerance test (ITT) and the
      frequently sampled i.v. glucose tolerance test (IVGTT) in normal, obese and
      hyperandrogenic women. SUBJECTS AND METHODS: Six normal, 6 obese and 12
      hyperandrogenic women of similar ages, were studied. In two consecutive days, the
      ITT and the IVGTT were performed and a basal blood sample was obtained to measure
      SHBG, DHEAS and IGFBP-1. Insulin sensitivity was calculated as the blood glucose
      slope in the ITT and with the minimal model of Bergman in the IVGTT. RESULTS:
      Insulin sensitivity, measured with ITT was 0.58 (0.53-0.63) in normal, 0.38 (0.05
      0.59) in obese and 0.20 (0.0-0.36) in hyperandrogenic women. The figures for the
      IVGTT were 7.97 (4.1-15.4), 2.41 (0.81-4.89) and 1.1 (0.46-1.88), respectively.
      Both methods had a positive correlation coefficient of 0.792 (p < 0.001). SHBG
      was 87.0 m 37.9 and 18.3 nmol/l in normal, obese and hyperandrogenic women,
      respectively (p < 0.09). IGFBP-1 values were 3.0, 2.1 and 1.6 ng/ml respectively
      (p < 0.05). DHEAS values were 132, 190 and 206 ug/dl, respectively (ND).
      CONCLUSIONS: ITT is a simple and reliable method to assess insulin sensitivity.
      SHBG discriminates subjects with different levels of insulin sensitivity. Since
      it is easy to measure, it could be used as a marker on insulin sensitivity.

PMID- 9595789
TI  - [Incidence of congenital malformations in 10 Chilean maternity hospitals that
      participate in the ECLAMC. Comparison of 3 periods (1971-1977, 1982-1988, 1989
      1994)].
AB  - BACKGROUND: The Latin American Collaborative Study of Congenital Malformations is
      an epidemiological surveillance system for congenital malformations that operates
      in 11 Latin American Countries. AIM: To report the incidence of congenital
      malformations in 8 Chilean maternity hospitals participating in this study,
      between 1989 and 1994. MATERIAL AND METHODS: During the study period, 133,564
      newborns and 1,196 stillbirths from 8 Chilean maternity hospitals were examined.
      These results were compared with those of a similar survey performed in 1982
      1988. RESULTS: The proportion of stillbirths in the study period was 0.88%. There
      were 3,268 malformed newborns (2.42%) and 125 malformed stillbirths (10.45%).
      These proportion of malformations among newborns were lower and among stillbirths
      were higher than those reported for the rest of Latin American countries. When
      comparing the results with the previous survey, a reduction in the proportion of
      malformations among newborns was observed. However, in all Latin American
      countries, the prevalence of malformations in newborns and stillbirths increased
      in this period. In the period 1969-1995, in one Chilean hospital, maternal ages
      and the proportion of congenital malformation showed parallel and rising curves.
      CONCLUSIONS: This survey shows some differences in the prevalence of congenital
      malformations, when the figures are compared with other Latin American countries
      and with previous surveys.

PMID- 9595788
TI  - [Molecular diagnosis of salt wasting congenital adrenal hyperplasia, caused by
      deficit of 21-hydroxylase, in the Chilean population].
AB  - BACKGROUND: The most frequent cause of congenital adrenal hyperplasia, manifested
      as virilization and salt wasting, is the deficit of 21-hydroxylase. This disease
      is originated by mutations of the gene CYP21 that codifies this enzyme, mostly
      recombination between this gene and its inactive pseudogene called CYP21P. AIM:
      To study the molecular origin of this enzyme deficiency in Chilean patients.
      PATIENTS AND METHODS: Twenty five patients with salt wasting congenital adrenal
      hyperplasia, that had 17-hydroxyprogesterone levels above 30 ng/ml, were studied.
      In all patients, a polymerase chain reaction (PCR) with selective primers was
      done with extracted genomic DNA, to amplify the active gene and specific primers
      for normal or mutated alleles (Allele-specific PCR). RESULTS: The affected allele
      was identified in 39 (78%) of the 50 chromosomes of the 25 patients. The higher
      frequency affected the ASIn2 in 26% of cases, followed by mutations Arg357Trp in
      22% of cases and Gln319Stop in 12% and deletion in 12%. The identification of two
      affected alleles in a same patient was achieved in 17 cases (68%). The most
      frequent genotypes were homozygosity for ASIn2 (16%), homozygosity for Arg357Trp
      (12%) and the homozygote deletion of the gene in 12%. CONCLUSION: The most
      frequent mechanisms of genetic damage in this population of patients with salt
      wasting congenital adrenal hyperplasia due to deficiency of 21-hydroxylase were
      the mutations ASIn2 and Arg357Trp. This type of studies allows prenatal diagnosis
      and genetic counseling.

PMID- 9595791
TI  - [Ethical problems in the biomedical research projects, presented to the Ethical
      Committee of the Medical School at the Pontificia Universidad Catolica of Chile].
AB  - BACKGROUND: The higher methodological complexity of either diagnostic or
      therapeutic procedures has raised concern about the ethical principles that
      should underlie the conduct of biomedical research involving humans. AIM: To
      evaluate ethical problems of research proposals submitted to an ethics committee.
      MATERIAL AND METHODS: All research proposals involving humans, submitted within a
      two years period to the ethics committee of the School of Medicine of the
      Catholic University, were retrospectively reviewed. "Ethical problem" was defined
      as any explicit disagreement with the ethical principles and guidelines for the
      protection of human subjects involved in biomedical research, according to the
      Helsinki declaration. RESULTS: In 20 of 44 reviewed projects, an ethical problem
      was identified. The most common problems were the absence or inadequacy of the
      informed consent, the justification of the use of placebo and problems related to
      the methodological aspects of the research, particularly the lack of an adequate
      control group when the potential benefits of a new drug were evaluated.
      CONCLUSIONS: According to the Nuremberg code, the Helsinki declaration and the
      International Principle of Ethics in Biomedical Research, we analyse ethical
      problems and suggest judgement elements for them.

PMID- 9595790
TI  - [Measurement of maximal oxygen uptake in a Chilean population sample].
AB  - BACKGROUND: Maximal oxygen uptake is considered by the International Biological
      Programme as the international standard of cardiorespiratory adequacy and
      physical condition. AIM: To measure maximal oxygen uptake in normal Chilean
      subjects, to establish normal reference values. SUBJECTS AND METHODS: Maximal
      oxygen uptake was measured in 2,203 subjects (451 women) aged 7 to 66 years old,
      during maximal exercise in a cyclo-ergometer or treadmill. This sample included
      trained sportsmen. RESULTS: Maximal oxygen uptake in men was 3.4 +/- 0.8 Vmin
      (range 1.1 to 5.6) or 55.2 +/- 9.2 ml/kg/min (range 23.8 to 83.2). In women, the
      figures were 2.55 +/- 0.55 l/min (range 0.87 to 3.82) or 47.5 +/- 8.0 ml/kg/min
      (range 20.8 to 76.3). These values decrease 0.65 ml/kg/min per year of age.
      CONCLUSIONS: These values can be useful as a normal reference for
      epidemiological, clinical or sportive purposes.

PMID- 9595792
TI  - [Study of the survival of elderly patients in intensive care units. Should they
      be admitted to these units?].
AB  - BACKGROUND: An important increase in health care costs has occurred lately,
      determined in part by the expenses of intensive care units. An important
      proportion of beds in these units are occupied by elders, with high costs and
      dubious results. AIM: To study the survival of elderly patients in intensive care
      units to shed light on the question if these patients should be admitted to these
      facilities. MATERIAL AND METHODS: We retrospectively analyzed the mortality of
      443 patients older than 65 years old, admitted to an intensive care unit between
      1993 and 1994. The mortality was compared with that of 334 younger patients
      admitted in the same period. Severity of disease was determined using admission
      APACHE II score. RESULTS: Older patients had a higher admission APACHE score than
      younger subjects (18.4 +/- 8.4 and 14.5 +/- 8.7 respectively, p < 0.01).
      Mortality during the intensive care unit stay was similar in older and younger
      patients (18.5 and 14.4%, respectively). Hospital mortality was also similar
      (22.4 and 25.9%, respectively). Older patients had a higher frequency of chronic
      diseases and degree of functional impairment. Mortality rates for different
      diseases were also similar in older and younger patients. CONCLUSIONS: Older age
      was not associated with a higher mortality during intensive care unit stay.
      Prognosis is determined by the admission severity score and the number of
      concomitant chronic diseases.

PMID- 9595793
TI  - [Neurosensorial hearing loss caused by noises: results of a longitudinal study in
      iron and steel workers].
AB  - BACKGROUND: The detrimental effect of noise in the ear is well known. However,
      several countries debate the acceptance of hearing loss caused by exposure to
      noise as a professional disease. AIM: To assess the association of noise levels
      in an industrial environment with neurosensorial hearing loss. SUBJECTS AND
      METHODS: One thousands two hundred thirty two workers exposed to low, moderate
      and high noise levels were studied. All had a normal admission audiogram and at
      least one further audiogram. RESULTS: Four hundred forty five subjects, aged 40.4
      +/- 8.2 years old, were exposed to low environmental noise, 341 subjects, aged 39
      +/- 7.8 years old were exposed to moderate noise and 446, aged 39.2 +/- 7.3 years
      old were exposed to high noise for 16.7 +/- 8.1, 14.8 +/- 7.7 and 15.2 +/- 7.6
      years respectively. The prevalence of hearing loss was 7.2, 11.7 and 13.2% among
      those exposed to low, moderate or high environmental noise. According to our
      legislation 0.4, 1.5 and 2.5% of those workers had a hearing impairment entitled
      to compensation. The regression slope for hearing loss was 0.5, 0.7 and 0.8
      dB/year of age in workers exposed to low, moderate and high noise levels
      respectively. A significant effect of noise was observed after the age of 40 in
      those exposed to high levels, and after the age of 50 in those exposed to
      moderate levels. CONCLUSIONS: According to our safe noise exposure criteria, we
      are accepting that 18.2% of workers will suffer a disabling hearing loss at the
      end of their job life and that 0.4% will not attain an economic compensation in
      spite of their impairment.

PMID- 9595794
TI  - [Radiosurgical labeling of non-palpable mammary lesions].
AB  - BACKGROUND: The frequency of breast cancer is increasing worldwide and
      mammography allows the diagnosis of concealed lesions. AIM: To assess the
      diagnostic yield for carcinoma of non palpable lesions detected by mammography.
      PATIENTS AND METHODS: We studied 46 patients, aged 24 to 67 years old, in whom a
      radiosurgical labeling of non palpable mammary lesions was performed. In all
      patients, a surgical biopsy was obtained, but the pathological study was
      available in only 40 patients. RESULTS: The mammographic appearance of lesions
      were microcalcifications in 40% of women, stellate images in 27.5%, asymmetry in
      density in 5% and the association of microcalcifications and other signs in 20%.
      Seventy seven percent of lesions were benign. Four patients had an in situ ductal
      carcinoma, two had a predominantly in situ carcinoma and 4 had an invasive ductal
      carcinoma. CONCLUSIONS: Our results are similar to those reported abroad. The
      finding of 5 minimal carcinomas underscores the effectiveness of mammography as a
      screening method for breast cancer.

PMID- 9595795
TI  - [Nocturnal hypoxemia after abdominal surgery: associated factors and usefulness
      of oxygen therapy].
AB  - BACKGROUND: Postoperative nocturnal hypoxemia (PONH) is a main factor in the
      genesis of respiratory, cardiac and neurologic complications after surgery. AIM:
      To describe the phenomenon of PONH after elective laparoscopy and laparotomy, and
      to evaluate the usefulness of oxygen therapy in its prevention. PATIENTS AND
      METHODS: Fifteen elective patients (6 M, 9 F, 51 +/- 8 years old) scheduled for
      laparotomy (n = 8) or laparoscopy (n = 7) were studied. Ventilatory parameters
      and pulse oximetry were measured pre and postoperatively. Patients were randomly
      assigned to receive oxygen by nasal cannula either during the first or the second
      postoperative night. RESULTS: PONH (SatO2 < 85) developed in seven patients
      (47%), of which four had undergone laparoscopic surgery. PONH was more frequent
      in mildly obese patients and those presenting preoperative hypoxemia (p = 0.03).
      Peak Flow was lower in patients presenting PONH (p = 0.04). In five patients,
      PONH was associated with significant tachycardia. Oxygen administration was
      associated with a higher SatO2 and prevented PONH in 6/7 patients. CONCLUSIONS:
      PONH is a common event in patients older than 40 years scheduled for open or
      laparoscopic abdominal surgery, and develops more frequently in those with
      preoperative nocturnal hypoxemia and greater ventilatory impairment. PONH can be
      prevented, most of the time, with oxygen administration.

PMID- 9595796
TI  - [Importance of pre-analytical variables in the quality of arterial blood gas
      determination].
AB  - BACKGROUND: Several frequent errors in the measurement of arterial blood gases,
      shed doubts on their real usefulness. AIM: To identify sampling, manipulation and
      transport errors in the measurement of arterial blood gases. MATERIALS AND
      METHODS: Three hundred and nine consecutive arterial blood samples received at
      the central laboratory of a public hospital were analyzed. Patient data in the
      order form, reception conditions at the laboratory, transport media, time of
      arrival and analysis of each sample were recorded. RESULTS: Five percent of
      orders informed the hour of sampling, 0.6% the patient's temperature and 18.1%
      the inspired oxygen fraction. Bubbles or clots were present in 12.9% and 3.2% of
      samples respectively, 87.3% of samples were well sealed and the amount of blood
      withdrawn in relation to the syringe capacity was optimal in 47.2% of cases.
      Ninety three percent of syringes were transported with ice cubes that did no
      cover the syringe and 5.8% of samples were received at room temperature. The
      delay in analysis, since the time of reception at the laboratory, ranged from 0
      to 55 min (mean 12.9 min). CONCLUSIONS: Several deficiencies in pre analytical
      variables in blood gas analysis were identified, most caused by neglect and
      susceptible of correction. Quality controls for this determination should be
      performed frequently.

PMID- 9595797
TI  - [Functioning and non-functioning parathyroid cysts: entities with different
      origin and clinical characteristics in 2 cases].
AB  - We report two women presenting with parathyroid cysts. A 20 years old woman
      presented with goiter and a cystic lesion in the left thyroid lobe was identified
      on ultrasound examination and CAT scan. The patient had hypercalcemia and
      elevated PTH levels. The content of the cyst, obtained by needle aspiration, had
      an extremely high PTH concentration. The patient was operated, removing the cyst
      and a remaining thymus. Pathological study confirmed the diagnosis of a
      parathyroid cyst. An 11 years old girl presented with a mass in the left thyroid
      lobe. An ultrasound examination disclosed the presence of a cystic nodule. The
      patient was otherwise asymptomatic and laboratory work up was normal. The patient
      was operated and pathological examination of the surgical piece revealed a
      parathyroid cyst.

PMID- 9595798
TI  - [Dysenteric syndrome, acute renal failure and lethal septic shock associated to
      Salmonella enteritidis infection. Report of 3 cases].
AB  - Chile is being affected by an epidemic of S enteritidis infections since 1994, an
      increasingly important cause of morbidity worldwide. Although infections by this
      bacteria have been commonly associated to diarrhea and patients are usually not
      affected by complications, three patients required admission by dysentery (not
      reported in most published series), acute renal failure (ARF) and septic shock
      (SS), respectively, at the end of the summer season. S enteritidis was isolated
      from stool cultures in all three cases. A female patient (24) with disentery
      presented with fever and diarrhea associated with blood and mucus and localized
      abdominal pain in the lower right quadrant. Surgery was not required although
      laparotomy was considered in the first hours after admission. ARF was
      demonstrated in a male patient (50) by dehydration, increased creatinine plasma
      and BUN level (7, 19 and 103 mg/dl, respectively), and increased urinary Na level
      and anion gap (35 mEq/l). Hemodialysis was not required. A third patient was
      admitted by SS (male, 57, alcoholic), as demonstrated by hypotension despite
      fluid reposition, altered mental status, and multiorgan compromise. Haemodynamic
      monitorization showed a high cardiac index and a low systemic vascular
      resistance. CPK serum determinations indicated rhabdomyolysis. Patients recovered
      satisfactorily, except SS patient, who died.

PMID- 9595799
TI  - [Ecology and health in Chile: present and future development].
AB  - In response to the progressive environmental deterioration, the Ecological
      Society of America has made a proposal, called "Sustainable Biosphere
      Initiative", to do research, teaching and decision making processes on
      biodiversity, global change and the effects of human activities on environment.
      The goal of appropriate environmental protection and welfare for mankind includes
      health and quality of life. Presently, Chile faces a number of environmental
      problems such as pollution, excessive urban growth, loss of agricultural areas,
      disposal of solid waste and species extinction. The lack of education and
      information in Chile, on these problems, is worrisome. The role of universities
      to overcome this deficit should be crucial in the future sustainable development
      of Chile.

PMID- 9595800
TI  - [Human races and hemato-sero-anthropology. Origin of Chilean natives and natives
      from Easter Island in the context of human races].
AB  - Geographical hematology of Bernard and Ruffie, or Hemato-sero-anthropology,
      intends to establish relationships between hereditary genetic characters of the
      blood and human races. Blood groups, haptoglobins, abnormal hemoglobin and other
      biological traits such as color vision are related to the origin of human races,
      their geographical distribution, history, settlements, drifts, invasions,
      customs, religious beliefs, cult to ancestors, dead modifications, culture,
      language, writing, sculpture, painting and pottery. Our investigations are aimed
      to locale Chilean natives and natives from Easter Island in the context of human
      races.

PMID- 9595801
TI  - [Recommendations for active immunization in patients with altered
      immunocompetence and/or with specific risks. Consulting Committee on
      Immunizations, Chilean Society of Infectology].
AB  - Although vaccines are powerful public health tools, are unwarrantedly denied or
      incompletely administered to patients with altered immunocompetence. The Advisory
      Immunization Committee presents an updated revision, according to the local
      epidemiological reality, that may guide the care of these patients.
      Recommendations are centered in patients with congenital immunodeficiencies, HIV
      infected individuals, offspring of HIV infected mothers, and subjects with
      medical conditions that increase the susceptibility towards one or more
      infectious disease. In each case, the indications and contraindications of
      immunizations included in the Extended Immunization Program or special vaccines,
      recommended for special groups, are analyzed. Special situations that must be
      considered in each risk group are also analyzed.

PMID- 9595802
TI  - [Medical care in 7 Chilean cities].
AB  - BACKGROUND: In countries with an intermediate development level such as Chile,
      health care is the main factor that improves the health status of the community.
      AIM: To inform the results of morbidity and medical care surveys performed in the
      Chilean cities of Antofagasta, La Serena, Concepcion, Temuco, Llay Llay, Tiltil y
      Lampa-Batuco. MATERIAL AND METHODS: A random sample of 951 dwellings with 4,192
      people was selected and studied three times, in 1995 and 1996. All health events
      (acute and chronic disease episodes, accidents, health examinations, dental care)
      and the main features of medical care were registered in the interviews which
      covered a 2-week period each time. RESULTS: Half of sick people received medical
      care and the rest was managed with self care techniques. Sixty nine percent of
      subjects with acute diseases received medical care, compared to 32% of those with
      chronic diseases. The National Health Fund (FONASA) financed most of these
      medical attentions, half of these were done in private centers and the rest in
      public premises. Private centers took care of 71% of acute patients, 48% of
      chronic patients and 27% of health controls. The proportion of private care in
      different cities paralleled the income of their populations. An estimation of 3.5
      medical attentions per capita per year in these cities can be reached. Health
      care was considered very good by 33% of patients, as good by 55%, as regular by
      9% and as deficient by 3%. Quality of care of private centers was perceived as
      better than that of public centers. Eighty five percent of sick people that did
      not seek medical care, did so due to the mildness of their ailments. People had
      to afford a mean of US$ 30 per episode of acute disease, US$ 32 per episode of
      chronic disease and US$ 56 per each dental attention. CONCLUSIONS: Two thirds of
      patients with acute diseases and one third of patients with chronic diseases
      received medical care during the study period.

PMID- 9595804
TI  - [Evidence-based medicine].
AB  - The need to improve the quality of health care and to contain its costs has
      become mandatory. Simultaneously we are confronted by a growing body of clinical
      information, most of it irrelevant. This paper describes the origin and methods
      of Evidence-Based Medicine, a new alternative to the usual ways of medical
      information. The recent development of computerized data bases is permitting the
      rapid location of relevant clinical information concerning specific questions on
      diagnosis, therapy or prognosis. Critical analysis is then used to determine the
      validity of the evidence obtained, which can be employed in clinical decision
      making. The future role of Evidence-Based Medicine in education and clinical
      practice seems highly promissory.

PMID- 9595803
TI  - [Mortality due to traffic accidents in Chile, 1994: an epidemiological approach].
AB  - BACKGROUND: Traffic accidents are one of the most important public health
      problems in the world and produce social, work and human resources losses. AIM:
      To perform an epidemiological description of traffic accidents occurred in Chile
      during 1994. MATERIAL AND METHODS: Data were obtained from death certificates in
      which the cause of death was a traffic accident. All death certificates obtained
      by the National Institute of Statistics during 1994 were used. Social,
      demographic and seasonal variables were recorded. RESULTS: During 1994, there
      were 1679 deaths due to traffic accidents (81% male), with a rate of 19.6 per
      100,000 inhabitants. Gender specific risks were 19.62 and 4.48 for men and women,
      respectively. Mean age at the moment of death was 39 years old. Fifty three
      percent of deceased people were single, 42% married and 5% widowers. Ten percent
      had no formal education, 48% had basic education, 23% college education and 6.5%
      university education. Seventy seven percent of fatalities occurred in urban
      areas. The risk of death by traffic accidents was 7.02 per 100,000 inhabitants in
      the metropolitan region. CONCLUSIONS: The information obtained in the present
      study may help to generate preventive strategies to control deaths caused by
      traffic accidents.

PMID- 9595805
TI  - [Meningococcal meningitis and chaos].

PMID- 9595807
TI  - [Medicine today: reflexions].

PMID- 9595806
TI  - [Nuclear medicine test reports].

PMID- 9595808
TI  - Meta-analysis in evidence.

PMID- 9595809
TI  - When should the physician question information disseminated by the pharmaceutical
      industry?

PMID- 9595810
TI  - Providing access to evidence-based information in reproductive health: the WHO
      reproductive health library for developing countries.

PMID- 9595811
TI  - Hormonal receptors in mammary carcinoma: comparison between quantitative and
      qualitative methods.
AB  - Alternatives to the traditional hormone receptor dosages for prognostic
      evaluation and clinical approach to breast cancer have been proposed for
      immunohistochemical determinations. For correlation purposes, such procedures
      were compared in 37 patients presenting 5 to 15 years of survival. Considering 30
      fm/mg as the positivity index, the disagreement between both methods reached
      35.1% with estrogen and 48.5% with progesterone receptors. When the positiveness
      level was changed to 20 fm/mg, the discrepancies were reduced to 32% with ER and
      increased to 57% with PgR. This study leads us to not recommend the
      immunohistochemical method applied to paraffin sections as an alternative
      procedure to the dextran-charcoal dosage for prognosis and therapeutic management
      of mammary carcinoma.

PMID- 9595812
TI  - Ligation of the left renal vein in epm1-Wistar rats: functional and morphologic
      alterations in the kidneys, testes and suprarenal glands.
AB  - OBJECTIVE: The ligation of the left renal vein (LLVR) in man is a controversial
      procedure in view of the risks of lesion to the renal parenchyma. With the
      objective of studying the morphologic and functional alterations caused by these
      lesions, we conducted experimental research with rats. MATERIAL AND METHODS: 64
      male adult EPM1-WISTAR rats were used, divided into 8 groups-4 for LLRV and four
      for control. Each LLRV group and corresponding control group were sacrificed
      progressively on the 7th, 15th, 30th and 60th day after the initial surgery.
      RESULTS: We found morphofunctional alterations only in animals that underwent
      LLRV in the four periods of sacrifice. The proteinuria creatinine in serum,
      testosterone in serum and serum corticosterone in serum showed practically no
      alteration in relation to the normal values for rats. Statistically significant
      severe histological lesions were found in the kidneys and testes of the LLRV
      groups. Lesions in the suprarenal glands were also present in these groups, but
      no sufficient to demonstrate statistical significance. CONCLUSION: Based on these
      results we can conclude that the ligation of the left renal vein is a procedure
      of high risk in these animals.

PMID- 9595813
TI  - Inhibitory serum factor of lymphoproliferative response to allogeneic cells in
      pregnancy.
AB  - INTRODUCTION: An inhibitory serum factor of mixed lymphocyte culture (MLC) has
      been associated with successful pregnancy after lymphocyte transfusion in women
      with unexplained recurrent spontaneous abortions (RSA). OBJECTIVE: Investigate
      whether the inhibitory serum factor of MLC is essential for a successful
      pregnancy. METHOD: Sera from 33 healthy pregnant women and from 40 women with RSA
      were assessed by a one-way MLC in which the woman's lymphocytes were stimulated
      with her partner's lymphocytes or with third party lymphocytes. RESULTS: An
      inhibitory serum effect (inhibition > 50% as compared to normal serum) was
      detected in 45% of the pregnant women who had at least 1 previous parity, in 8%
      of the primigravidea, in 29% of those with one abortion and in 58% of those with
      more than one abortion. CONCLUSION: MLC inhibitory serum factor does not seem to
      be an essential factor for pregnancy development. Therefore, it should not be
      considered as a parameter for the assessment of RSA patients.

PMID- 9595814
TI  - Studies on the components of the contact phase system in patients with acute
      nonlymphoblastic leukemia.
AB  - The objective of the present study was to evaluate factors of the plasma
      kallikrein system in patients with acute nonlymphoblastic leukemia (ANLL), and
      compare the results to a normal control group. A prospective study was performed
      in the Tertiary Health Care Institution, Hemocentro, Campinas State University,
      Campinas, Sao Paulo, Brazil. Thirty-five patients, diagnosed as ANLL between 1988
      and 1991, were considered for participation. Eleven patients were not eligible,
      according to the exclusion criteria: infection/septicemia, previous treatment or
      blood transfusion. The study was performed with 24 ANLL patients, average age 34
      years (16-69 years), 14 men and 10 women. Nineteen healthy volunteers, workers
      from the Hematology Center, average age 32 years (21-59 years), 11 men and 8
      women, were the control group. Plasmatic prekallikrein, C1-inhibitor, alpha 2
      macroglobulin, activated partial thromboplastin time, prothrombin time, factor
      XII, factor XI, factor V and prealbumin were measured. Plasmatic prekallikrein (p
      = 0.02) and prealbumin (p = 0.03) were significantly decreased, and prothrombin
      time increased (p = 0.003) in the patient group when compared to the control.
      Significant correlation (r = 0.49, critical value = 0.43, p < 0.05) between
      prekallikrein and prealbumin, and between prothrombin time and factor V (r =
      0.54, critical value = 0.44, p < 0.05) was demonstrated in the patient group. No
      correlation was found between parameters analysed and circulant blast count or
      leukemia subgroups. Statistical analysis was performed by the Wilcoxon test.
      Correlation between the parameters was also verified. These results suggest
      activation of the contact system or impaired liver synthesis in patients with
      ANLL, and could contribute to disease complications.

PMID- 9595815
TI  - Upper extremity nerve lesions (diagnosis, indications, surgical techniques).
AB  - OBJECTIVE: Revision and questioning of orthodox principles regarding the
      conduction of nerve impulse. DESIGN: Retrospective study with clinical analysis
      of results. SITE: Hospital das Clinicas (HCFMSP), public university institution
      with research programs and tertiary attention to health. GROUP MEMBERS: Author
      and a team of residents and trainees. OPERATION: Direct suture of nervous stumps
      utilizing auxiliary technical procedures:- joint-flexion, nerve transposition,
      tendon transplants, bone shortening. MEASUREMENT: Clinical evaluation and
      objective tests for tactile and stereognostic function recovery (Weber Test).
      RESULTS: Variable, depending on preoperative conditions:- type of lesion, time
      elapsed since injury. CONCLUSIONS: Neurorrhaphy should be the procedure of choice
      even for long term lesions, although the expected results may be less favourable.
      Periodical evaluation from 24 hs. postoperative, checking for early undefined
      signals of nervous function recovery. Association of specific drugs for chemical
      biophysics of the nerve.

PMID- 9595816
TI  - Lymphoblastic transformation of myelodysplastic syndrome.
AB  - Mielodysplastic syndromes (MDS) are clonal disorders of the hemopoietic stem
      cell. About one third of the cases terminate in an acute leukemia, usually acute
      myeloblastic leukemia. However, few cases of transformation into acute
      lymphoblastic leukemia (ALL) have been described. We present a case of refractory
      anemia that transformed into ALL two months after diagnosis and was successfully
      treated with conventional chemotherapy. Two years later a hyperfibrotic form of
      MDS was detected in the patient, that soon after terminated in acute
      megakaryoblastic leukemia. The course of MDS in the present case provides
      evidence that MDS can involve a pluripotent stem cell, presenting clonal
      evolution, documented by successive changes in its clinical and hematological
      features.

PMID- 9595817
TI  - del 11(q23) as a prognostic factor of iron overload in refractory anemia with
      ringed sideroblasts.
AB  - We present the case of a patient with MDS RARS subtype with loss of part of the
      long arm of chromosome 11 del 11(q23). This a cytogenetic abnormality that occurs
      in 7% to 20% of RARS cases not related to poor prognosis. It seems that this
      deletion is a marker of iron overload in MDS.

PMID- 9595818
TI  - Spontaneous rupture of the esophagus: report of two cases.
AB  - OBJECTIVE: To study the diagnosis, prognosis and management of spontaneous
      rupture of the esophagus. DESIGN: This is a retrospective study through the
      analysis of two cases with delayed diagnosis and subsequent treatment at the
      Track Surgery Service. LOCALE: The study was performed at the Thoracic Surgery
      Unit of the Hospital do Servidor Publico Estadual Francisco Morato de Oliveira in
      the city of Sao Paulo. This is a specialized service. PARTICIPANTS: The two
      patients reported on had suffered spontaneous rupture of the esophagus. They were
      transferred to the Thoracic Surgery Unit because of the worsening of their
      condition in the previous institution which they had been admitted into.
      MEASUREMENT: The two patients with esophagus pleural fistula received similar
      treatment, initially advocated by Kanashin in Russia and Hauer-Santos in the
      United States, which consists of washing the fistula and using continuous pleural
      aspiration. RESULTS: Although both patients had to spend a long period of time in
      hospital, their evolution was satisfactory with the treatment adopted, and the
      fistula closed. CONCLUSION: The authors conclude that the method of lavage of the
      mediastinum and continuous pleural aspiration, in patients who after spontaneous
      rupture of the esophagus developed a pleural esophagus fistula due to belated
      diagnosis, is an alternative and satisfactory therapy. Furthermore, in order to
      have the best outcome, an early diagnosis is recommended and thoracostomy as the
      surgical procedure, with primary suture.

PMID- 9595819
TI  - [Clinical subgroups of anxiety disorders: from phenomenology to cluster
      diagnosis].
AB  - The panic disorder is heterogeneous. The factorial study of the phenomenology of
      panic crisis suggests the existence of different subtypes: the cardio
      respiratory, the vestibular, the despersonalization, the gastrointestinal and
      others. We review the clinical and biological data which suggest the display of
      these subtypes.

PMID- 9595821
TI  - [Risperidone in the treatment of acute exacerbation of schizophrenia symptoms].
AB  - A total of 439 schizophrenic patients according to ICD-10 criteria was included
      in an open label postmarketing surveillance study to evaluate the efficiency of
      resperidone as maintenance treatment of the schizophrenic acute exacerbation. The
      efficiency of risperidone was assessed according the number of patients who
      responded to treatment, the duration of the hospitalization period an the
      decrease in the total score as well as in the different clusters of the Brief
      Psychiatric Rating Scale (BPRS) during the study period. A patient was considered
      as responder to treatment when a decrease of, at least, a 20% was achieved in the
      total BPRS score while being treated in monotherapy with risperidone. Safety was
      evaluated by the UKU subscale for neurological side effects and spontaneous
      reports. Patients were evaluated at baseline and weeks 1, 2, 6 and 12. Forty
      patients (9.1%) were excluded from the statistical analysis due to protocol
      violation. Eighty one patients (20.3%) dropped out due to lost for follow-up (n =
      25; 6.3%), new hospitalization (n = 23; 5.8%), inefficacy (n = 12; 3%), side
      effects (n = 7; 1.8%) and others (n = 14; 3.5%). Risperidone was used at doses
      between 1.5 and 19 mg daily (mean dosage: 7.66 +/- 3.07 mg daily). The duration
      of the hospitalization when dosages of risperidone of less than 6 mg daily were
      used was 32.1 days. However, when higher dosages were used, the number of days in
      hospital decreased (26.6 days at dosages between 6 and 9 mg daily and 25.3 days
      when dosages higher than 9 mg daily were used). There was a significant
      reduction, versus baseline, in the BPRS mean total scores as well as in it's
      different clusters. (positive symptoms, negative symptoms, anxiety/depression)
      from week one onwards. At week 1, 66.9% of the patients had an improvement (20%
      versus baseline in their BPRS total score. At the end of the study period, 93.2%
      of the patients had an improvement (20% in their BPRS total score. There was a
      significant reduction in the total UKU subscale for neurological side effects
      scores (p < 0.005) from week 1 onwards, as well as for the total score of the
      following symptoms: rigidity, hypokinesia, hyperkinesia tremor and akatysia.

PMID- 9595820
TI  - [Pattern of usage of new antidepressants in clinical practice].
AB  - INTRODUCTION: Data from naturalistic studies have reported differences in the
      clinical use of antidepressants referring to the need for adjusting doses,
      treatment duration, tolerability and use of concomitant medication. These
      differences could be considered as an indicator of the effectiveness of
      antidepressants in clinical practice settings. OBJECTIVES: It is a naturalistic,
      retrospective, observational study which objective is to evaluate and compare the
      pattern of antidepressant use (fluoxetine, fluvoxamine, paroxetine, sertraline,
      venlafaxine) and to establish if there is a relation between the different
      pattern of use and the effectiveness of them. DATA AND METHODS: A retrospective
      dataset of patients who initiated therapy on fluoxetine, fluvoxamine, paroxetine,
      sertraline, or venlafaxine with a follow-up period of 6 months was used.
      Information about clinical characteristics of patients and antidepressant pattern
      of use were collected. Pattern of antidepressant use were defined as: "initial
      doses", "upward dose titration", "augmentation strategy", "switching" and "early
      interruption of treatment". The efficacy of the therapy was assessed by the CGI
      improvement. RESULTS: Fluoxetine was the antidepressant more associated with a
      statistical significance (p = 0.001) to an stable pattern of use (initial doses
      without upward dose titration, switching or augmentation). After controlling for
      other observed baseline characteristics, patients who remained on their initial
      antidepressant therapy, with a stable pattern of use were 1.61 times more likely
      than patients who had an adjustment to therapy to experience a treatment
      response. Patients who initiated treatment with sertraline or venlafaxine were
      2.155 and 4.831 times less likely, respectively, to experience a response
      relative to patients who initiated therapy on fluoxetine. CONCLUSIONS: The need
      to upward dose titration, switching or augmentation in the treatment could be
      indicated a worse therapeutic control of the symptoms. Patients treated with
      fluoxetine are in a stable pattern of use more likely than patients in the other
      antidepressants, this fact is related with better global therapeutic results.

PMID- 9595822
TI  - [Gender differences in mental health: epidemiological study in the general
      population of the island of Formentera].
AB  - The epidemiological data of prevalence of mental disorders according to gender
      differences are controversial. We analysed the prevalence among men and women via
      a two-stage epidemiological community study using the GHQ-28 and the SCAN on the
      island of Formentera (Spain). There are no sex differences in total prevalence;
      nevertheless some significant differences are detected when data is analysed on
      specific disorders. Affective disorders, sleep disorders and neurotic and
      somatoform disorders are more prevalent among women, whereas men have more
      psychoactive substance use disorders. Comorbidity with medical illness are higher
      in women but differences are not significant. These findings suggest the need to
      standardise procedures and instruments in these kinds of studies. This is because
      one of the bias could be the difference in the number of disorders included in
      the instrument design used (in our study, sleep disorders and psychoactive
      substance use disorders were included and personality disorders were excluded.

PMID- 9595823
TI  - [Differential characteristics of families of adolescents and young adults that
      have attempted suicide].
AB  - INTRODUCTION: Families of adolescent and young adult suicide attempters are
      studied to analyze their role in these extremely dangerous behaviors. METHOD: 72
      adolescents and young adults (aged 15-24) who have made a suicide attempt and 72
      normal controls matched by sex, age and marital status, are studied in a case
      control design. Several aspects of each family are explored: composition, degree
      of stability in parental couple, type of relationships among the members, labor
      status of parents and medical-psychiatric and legal family history. RESULTS AND
      CONCLUSIONS: Only parameters analyzing parents-offspring interactions can
      differentiate both groups. Keep an unsatisfactory relation with any of the living
      parents are the family factors which place the young or adolescent subject in
      risk of making a suicide attempt in our surrounding.

PMID- 9595825
TI  - [Predominance of urban suicides over rural suicides in Spain].
AB  - INTRODUCTION: The different occurrence of Suicide depending on the rural/urban
      environment, as well as the interaction of this variable with others such as sex
      and age has given rise to a large quantity of investigations over the world. It
      was necessary to carry out in Spain an updated study of these characteristics.
      OBJECTIVE AND METHODS: Our purpose is to work with the raw data referred to
      suicide in the two last Spanish Census years. 4,619 records of suicide are
      requested and obtained from the Spanish National Statistics Institute registered
      in the years 1981 and 1991. Adjusted rates by rural/urban environment, sex and
      age are established and compared to each other. RESULTS AND CONCLUSIONS: Suicide
      rate in Spain is always higher in the cities that in the country, no matter be
      sex or the age group. However, there appears to be no continuous relationship
      between Suicide and the environment variable, since the large cities seem to
      confer a certain prevention. On the other hand, the feminine urban suicidal
      behaviour is becoming quantitatively more and more similar to those of men.

PMID- 9595826
TI  - [Psychosocial treatment of bipolar disorder].
AB  - INTRODUCTION: The bipolar disorder is an important health problem. It presents
      with severe sintoms, and it tends to cronify. Although lithium has a prophilactic
      role, it has not controlled the development of severe psychosocial complications.
      It is necessary to study the psychosocial aspects related to this disorder, to
      define the areas in which the psychosocial interventions are needed, and the
      types of psychosocial approaches that can be useful. METHODS: Review of the
      literature, through MEDLINE database in the last fifteen years, about
      psychosocial complications of bipolar disorder and its treatment. RESULTS: Many
      articles emphasize the important psychosocial deficits that appear in patients
      with bipolar disorder. These deficits concern to all social functions and persist
      for a long time. The patients are more vulnerable to stressing events, that can
      have devastating consecuences. The articles report the influence in the evolution
      and prognosis of this disorder, by the comorbidity of other medical and
      pschiatric problems. The psychotherapeutical interventions can be of interest to
      treat the social aspects that lithium fails to control. CONCLUSIONS: Our approach
      would tend to integrate in the clinical practice both, the biomedical and
      psychosocial theories. This permits an integral treatment of all the factors
      implicated in the genesis, maintenance, and consecuences of the mental disorders.

PMID- 9595824
TI  - [Child rearing patterns in mothers with postpartum depression].
AB  - INTRODUCTION: Postpartum Depression is a psychiatric syndrome with a prevalence
      of 10-15%. The studies show that depressive mothers have a "negative" relation
      with their children. METHOD: 205 primiparous women are analyzed, of them, we take
      a group of "cases" (23 depressive mothers) and a "control" group (37 women
      without psychiatric symptoms). Childrearing in the first postpartum year is
      analyzed. RESULTS: 13.5% of the studied women have a Postpartum Depression within
      the first six postpartum months. There aren't sociodemographics differences
      between both groups. Childrearing of depressive mothers is lower in affect and
      care than control mothers. CONCLUSIONS: Childrearing of depressive mothers in
      postpartum period is lower in Affect and Care than non depressive mothers in the
      same period.

PMID- 9595827
TI  - [Psycho-oncology: psychological disorders during autologous bone marrow
      transplantation].
AB  - Use of BMT (bone marrow transplatation) has rapidly grown in the last few years.
      It extends to a variety of neoplastic illnesses and hematological malignancies.
      This procedure includes implicit appearance of many and important stressors, both
      physical and psychological, due to the illness and to chemotherapy treatments,
      among which the appearance and severe colateral effects during the stay in
      hospital has a special relevance. The need to consider the influency of
      predictive variables like, prior experiences, optimistic vs. pesimistic
      expectancies and the strategies of coping used in the adaptation through the
      treatment, are a central point in the study of the fluctuations of the different
      psychological responses and their interrelation with the physiology symtomatology
      which are present during the different phases of the process of BMT.

PMID- 9595828
TI  - The effect of aqueous extracts from Inonotus obliquus on the mitotic index and
      enzyme activities.
AB  - The effect of aqueous extract from Inonotus obliquus on the mitotic index and
      some enzyme activities in human cervical uteri tumour cells HeLa S3 in vitro was
      evaluated. It was concluded that Inonotus extract inhibited the growth of tumour
      cells. The fungal extract caused a decrease of the cell protein amount and
      mitotic index value. Moreover, this extract disturbed metabolism in cells caused
      decreased activity of LDH, HBDH, MDH, GGT and increasing the activity of
      catalase.

PMID- 9595829
TI  - [The solubility and in vivo-in vitro correlation of naltrexone].
AB  - The dissolution of three dosages of Naltrexone tablets was studied, there being
      no monograph of this active principle in the most commonplace pharmacopoeia. The
      dissolution parameters were calculated "in vitro", then a correlation model was
      applied to determine the relationship between these parameters and the "in vivo"
      pharmacokinetic parameters of Naltrexone at each dosage level and also their
      degree of association. The regression lines between the "in vivo" and "in vitro"
      parameters were then plotted. Three C level correlations were obtained as per USP
      23 between the pharmacokinetic parameter Cmax and the dissolution parameters
      1/T50, E.D.30 and kd. The dissolution test conditions were also validated.

PMID- 9595830
TI  - Immune response to vaccine against influenza in smokers, non-smokers and, in
      individuals holding respiratory complications.
AB  - Levels of antibody against influenza virus were evaluated in serum pairing
      samples from individuals immunized against influenza by Hemagglutination
      Inhibition and Single Radial Hemolysis tests. For this purpose, groups of
      smokers, non-smokers and, of those holding respiratory complications, were
      formed. Results of serologic titrations pointed out to an increase in the level
      of antibodies for the smoker and non-smoker groups, with significant degrees of
      difference up to P < 0.001 difference between both averages after immunization.
      However, in the group of respiratory complications no significant differences (P
      > 0.05) were found out between the averages antibody levels for the subtype A
      (H1N1) and the Type B (vaccine components); an increase only at the level of
      antibodies was registered, with differences among the averages of the antibody
      levels, for the subtype A (H3N2) (vaccine component) at degrees of P < 0.01 and P
      < 0.001 on the titration of the SRH and HI tests, respectively. It can
      demonstrate that immunization against influenza presents a good protection for
      the smoker and non-smoker groups; however, in the group of respiratory
      complications it only occurred with the subtype A (H3N2), indicating that this
      subtype presents good antigenicity since it has induced better formation of
      antibodies, even in defective organisms.

PMID- 9595831
TI  - Development and evaluation of an ideal formulation of glibenclamide by solid
      dispersion techniques.
AB  - An attempt was taken to develop an ideal formulation of Glibenclamide.
      Considering the physico-chemical nature of the drug the solid dispersion system
      was utilised using hydrophilic and hydrophobic carriers and formulations were
      made by fusion as well as solvent evaporation/co-precipitation techniques. The
      resulting formulations were evaluated in respect of physical nature, yield, assay
      content and stability. The in vitro release profiles of the formulations were
      compared with the marketed tablet and simple physical mixtures having same
      composition of drug and excipients. The effects of various carriers as well as
      manufacturing procedures on the in vitro release rate of drug were also studied.
      It is observed that a suitable blend of different batches of solid dispersions
      containing hydrophilic and hydrophobic carriers will give an optimum formulation
      with quick onset and prolonged duration of action.

PMID- 9595832
TI  - [The new norms decreed by the legislative dirrective 91-93 CCE].
AB  - The Community law now rules any sector of the economy including the
      Pharmaceutical Industry, which is controlled with a special attention starting
      from drugs manufacturing up to marketing. After detailing the Community
      regulations acknowledged by the Italian legislation since the adoption of the
      first Pharmaceutical Directive in 1965, the Authors examine the Decree Law of
      february 1997 by which the EEC Directive 93/39 is acknowledged (as amended
      Directives EEC 65/65,75/318 and 75/319 relating to medicinal products for human
      use). A special attention is devoted to the several regulations concerning
      Pharmacovigilance, whose importance is emphasized.

PMID- 9595833
TI  - New quinazolinones-4. Antiinflammatory and anticonvulsant agents. New classes of
      pharmacologically active compounds.
AB  - The authors present the most interesting examples of anticonvulsant and
      antiinflammatory active quinazolinones-4 synthesized after 1990. There are also
      presented quinazolinones-4 belonging to new classes of pharmacologically active
      compounds-angiotensin II receptors antagonists and cholecystokinin receptors
      antagonists.

PMID- 9595834
TI  - Synthesis of some new biologically active 2,3-disubstituted quinazolin-4-ones.
AB  - The facile synthesis of 2-(2'-4-anisoylvinyl)-3-arylquinazolin-4-ones (2a, b)
      involves the condensation of 2-toluidine or 4-phenylenediamine with the
      corresponding 2-[2'-(4-anisoylvinyl)]-4H-3,1-benzoxazine-4-one (1). Reaction of
      compound 2 with aldehydes, bromine, alcohols, hydrazine hydrate, urea and
      thiourea are discussed. The former structure of the products have been
      characterized by elemental analysis and spectral data. Preliminary screening of
      some selected compounds for antimicrobial activity is reported.

PMID- 9595835
TI  - Dimethyltin(IV) carboxylate compounds; synthesis, characterization and in vitro
      cytotoxic activity.
AB  - Six dimethyltin(IV) carboxylate compounds of the general formula Me2SnX2, where X
      = 1/2 O2(CO)2 (oxalate), 1/2 O2(CO)2CH2 (malonate), 1/2 O2(CO)2CH = CH (maleate),
      1/2 O2(CO)2C-CH2CH2CH2 (cyclobutyl dicarboxylate), O(CO)C6H11 (cyclohexane
      carboxylate) and O(CO)CMe3 (pivolate) have been prepared and characterized
      physicochemically and spectroscopically. The cytotoxic activities of these
      carboxylates have been studied against HeLa, Hep-2, RD, L20B and P388 cell lines
      using the MTT-colorimetric assay. These activities were compared with the
      cytotoxic activities of the three reference standards, cisplatin, carboplatin and
      oxaliplatin. The compounds were X = 1/2 malonate, 1/2 maleate, cyclohexane
      carboxylate and pivolate exhibited a range of significant activities against the
      cell lines used, whereas no cytotoxic activities were exhibited by the rest of
      the six compounds. The significance of these results is given and discussed.

PMID- 9595837
TI  - Case management study: polyarthritis with fever.
AB  - In most cases, a thorough initial evaluation will reveal the cause of fever and
      polyarthritis. However, in some patients the initial diagnosis may be unclear
      and, as time passes, the characteristic clinical patterns emerge. Recurrent
      attacks are suggestive of other conditions such as crystal-induced arthritis,
      Lyme disease, and Mediterranean fever. In rheumatoid arthritis and Reiter's
      syndrome, the fever resolves and the articular findings predominate with the
      passage of time. Similarly, Still's disease is initially diagnosed on the basis
      of clinical criteria, and later confirmed by the evolution of chronic
      polyarthritis. Diagnostic approaches for the evaluation of patients presenting
      with acute arthritis have been published and are readily available (2,8,9). The
      most reliable way to establish the diagnosis for a rheumatic disease is
      thoughtful and thorough evaluation by an experienced clinician (3,10). Certain
      discriminating features and confirmatory tests can aid in the diagnosis of
      polyarthritis with fever (Tables 2 and 3).

PMID- 9595838
TI  - Parvovirus: a review.
AB  - Infections caused by human parvovirus B19 result in a variety of clinical
      manifestations, the severity of which depends on the immune and hematologic
      status of the host. Arthropathy is known to occur in children and adults with
      acute parvovirus B19 infection. In adults, the arthropathy is common and is
      usually brief and self-limited, although a chronic arthropathy due to HPV B19
      infections can occur rarely. It is important to differentiate between such
      chronic infection and RA, because of the similar clinical manifestations and
      different modes of treatment. An association between HPV B19 and other
      rheumatologic diseases such as vasculitis needs further research before
      confirmation is possible.

PMID- 9595839
TI  - Digital-image analysis of the rhomboid fossa surface.
AB  - Forty brainstems were investigated in order to evaluate morphological and
      morphometrical variability of the 4th ventricle floor. Visibility evaluation of
      the following rhomboid fossa structures: striae medullares, facial colliculus,
      superior fovea, vestibular area, sulcus limitans, incisure, medial eminence,
      median sulcus, vagal triangle, hypoglossal triangle and obex was performed. Obex,
      median sulcus, vestibular area, vagal and hypoglossal triangles were found to be
      sufficiently visible in all specimens. Facial colliculus was poorly visible in
      37% of the examined brainstems. Striae medullares were invisible in 30% of the
      analysed material and exhibited individual variability of a high degree in
      relation to their number and arrangement. Morphometrical study showed measured
      distances to be individually variable with a relatively low coefficient of
      variation of approximately 10%.

PMID- 9595841
TI  - Variability of the inferior temporal branches of the human posterior cerebral
      artery.
AB  - In 204 cerebral hemispheres the distribution of temporal branches were studied.
      These branches are: anterior inferior, intermediate medial, and posterior
      inferior. In most cases the inferior temporal branches arose from the posterior
      cerebral artery. In some cases they originated from the lateral occipital artery.

PMID- 9595840
TI  - Progress in myelin formation of the thoracic sympathetic trunk in human fetus
      aged 17 weeks.
AB  - In 17th week old fetus the interganglionic rami of the thoracic sympathetic trunk
      are mainly composed of bundles of unmylinated fibers. The well myelinated fibers
      have 11 compact myelin lamellae. Although many fibers are already myelinated,
      fibers in various phases of myelinogenesis are found.

PMID- 9595842
TI  - Cytoarchitectonics of the ganglia functionally connected with the chorda tympani
      of the Syrian hamster.
AB  - A study on cytoarchitectonics of the parasympathetic ganglia which are
      functionally connected with the chorda tympani, was carried out in the Syrian
      hamster. Histological (paraffin and historesin) techniques were applied. The
      investigated ganglia are agglomerations of up to forty cells in ganglia of
      different sizes (from 50 to 400 microns in diameter), dispersed in three regions:
      1. One large ganglion consist of 30 neurocytes in cross-sections and a few (3-4)
      smaller ganglia occurred within the hilus of the mandibular and major sublingual
      glands. 2. Along the main ducts of the salivary glands appear only 3 little
      ganglia, but at the level of crossing of these ducts with the lingual nerve-were
      found up to 12 large ganglia. 3. In the body and apex of the tongue the
      parasympathetic ganglia were dispersed mainly along ramifications of the lingual
      nerve. There were up to 20 agglomerations of cells different sizes and shapes.
      Because of this there is no justification in the hamster for distinguishing
      separate mandibular and sublingual ganglia.

PMID- 9595843
TI  - Arterial blood supply of the thoracic and lumbosacral parts of the spinal cord in
      Wistar rats.
AB  - The thoracic and lumbosacral parts of the rat's spinal cord are supplied by 1)
      ventral and dorsal radicular arteries which contribute to vascular trunk passing
      along the spinal cord, and 2) ventral and 2) dorsolateral spinal arteries. The
      dorsal radicular arteries in the thoracic part arise bilaterally at the same
      level and are more numerous and of lesser diameter than corresponding ventral
      radicular arteries. In the lumbar part the dorsal radicular arteries are also
      more numerous than ventral ones which were mainly found at the levels of L1, L2
      and L3. The sacral radicular arteries are present sporadically at the S1.

PMID- 9595844
TI  - Vascularization of the human sciatic nerve fasciculi.
AB  - The infrafascicular blood vessels of the sciatic nerve were investigated in 36
      nerves obtained during autopsy from males and females aged 20-72 years. Arteries
      of fasciculi form intrafascicular vascular net. The number of venous vessels
      draining blood from fasciculi is much greater than arterial vessels.

PMID- 9595845
TI  - Rare case of the accessory radial artery.
AB  - The accessory radial artery passed laterally to the brachial artery and then
      radial artery, and finally it anastomosed with the princeps pollicis artery.

PMID- 9595846
TI  - Anatomical relationships between the deep palmar arch and the deep branch of the
      ulnar nerve.
AB  - The relationship between the deep palmar arch (DPA) and the deep branch of the
      ulnar nerve (dbUN) was analysed in 60 hands from 30 formaldehyde treated cadavers
      of adult individuals, of both sexes, with age ranging from 21 to 70 years, in the
      Division of Descriptive and Topographic Anatomy of the Federal University of Sao
      Paulo (UNIFESP). The arteries were injected with neoprene latex and dissections
      were performed under a magnifying glass. DPA was ventral to dbUN in 50% of the
      cases (type I) and dorsal in 45% (type). In type I dbUN crossed the arterial arch
      at the following levels: in the 4th interosseous space in 17.9% of the cases, in
      the 3rd interosseous space in 21.4% and in the 3rd metacarpal bone in 39.3%. In
      type II dbUN crossed the arterial arch in the 4th metacarpal bone in 25.9% and in
      the 3rd intersseous space in 37%. The relationship between the nerve and the
      palmar metacarpal arteries was also studied. The data obtained may be of
      practical use in the surgery of the palmar region.

PMID- 9595847
TI  - Neuropathological syndromes in the course of full blown acquired immune
      deficiency syndrome (AIDS) in adults in Poland (1987-1995).
AB  - Morphological analysis of the brains from 100 cases of full blown AIDS patients
      observed in the course of 1987-1995 years was performed. The material comprised
      96 males, 3 females and 1 infant, 11 months old. Early material consisted almost
      exclusively of homo- and bisexuals, while in the last years heterosexual drug
      addicts prevailed. Gross brain examination revealed focal changes in 25% of
      cases, most of them being connected either with opportunistic infections or
      primary proliferating malignancies. Brain atrophy with an evident regional
      differences was observed macroscopically in 35 cases. Microscopic examination
      allowed detection of pathological changes in the brains of 87 cases, although in
      the remaining 13 cases there occurred some slight abnormalities taking the form
      of non-specific neuronal degeneration and loss, considered as resulting from
      perimortal cardio-pulmonary insufficiency or bleeding. Specific HIV-related
      changes in the form of HIV-encephalitis, HIV-encephalopathy or coexistence of
      both and HIV-leptomeningitis as well as HIV-vasculitis were present in 35 cases.
      They were accompanied by HIV-associated changes (vacuolar myelopathy, vacuolar
      leukoencephalopathy and selective poliodystrophy). Very seldom they appeared as
      independent pathological features and were characterized by very low frequency.
      Opportunistic infections composed the largest group of 59 cases. Proliferative
      malignancies occurred altogether in eleven cases, 10 of which were primary and
      secondary brain lymphomas. One case of Kaposi sarcoma completed the neoplastic
      series. Sixteen cases revealed various types of brain pathology such as
      hepatogenic encephalopathy, traumatic cortical scars, central pontine
      myelinolysis etc. The 59 cases of opportunistic infections consisted of a wide
      spectrum of viral and bacterial as well as fungal and protozoan infections. Among
      viral infections cytomegalovirus encephalitis was the most common, way ahead the
      progressive multifocal leukoencephalopathy. The second in frequency among
      opportunistic infections was brain toxoplasmosis and some fungal infections such
      as cryptococcosis and aspergillosis. Bacterial infections were in fact limited to
      tuberculosis, taking the form of granulomatous leptomeningitis with severe
      vascular pathology and/or tuberculoma formation. Many pathological processes
      appearing in a single case was characteristic feature of our collection. There
      was coexistence of HIV-specific CNS pathology and opportunistic infections,
      malignant neoplastic growth and other types of pathology. Various opportunistic
      infections coexisted without HIV-specific changes as well as malignant
      proliferation with opportunistic infections. Similarities and differences of our
      series were compared with data characterizing other, earlier collections of
      NeuroAIDS.

PMID- 9595848
TI  - The white matter changes in microencephalic HIV infected infants. A preliminary
      report.
AB  - The brains of six infants 14-34 months of age and with microencephaly (brain
      weight deficit 20-55.5%) were chosen from a group of cases vertically infected
      with HIV. The center of our investigations was focused on the white matter
      changes of which two types were observed in the examined brains. Within the
      periventricular white matter of four cases evident lesions consisting of myelin
      pallor and concomitant gliosis were recognized as HIV-1 infection related
      leukoencephalopathy. In all those cases myelination delay was also noted. In one
      case HIV encephalitis was diagnosed. Our observations suggest that in the
      majority of HIV infected infants changes resulting in the brain "too small for
      age" corelate with myelination delay coexisting with early-onset
      leukoencephalopathy. Because of the small number of cases in this study the
      results should be considered preliminary, and will require further
      investigations.

PMID- 9595850
TI  - Krabbe disease: an ultrastructural study of globoid cells and reactive astrocytes
      at the brain and optic nerves.
AB  - We report here a detailed ultrastructural study of a brain biopsy along with post
      mortem brain and optic nerve specimens from a case of Krabbe disease, a
      relatively rare leukodystrophy caused by a mutation in the gene for
      galactocerebrosidase (GALC) mapped to the 14q31 region of chromosome 14. GALC is
      responsible for lysosomal hydrolysis of several galactolipids including
      galactosylceramide, a major sphingolipids of the white matter of the central
      nervous system, galactosylsphingosine (psychosine) and galactosyldigluceride. The
      main neuropathological features such as accumulation of globoid cells, loss of
      myelin and marked gliosis were observed in the white matter. The monocytic origin
      of globoid cells was confirmed by CD-68 and ferritin-positivity and periodic acid
      Schiff (PAS) positivity. Ultrastructural study of the globoid cells showed the
      accumulation of tubular crystalloids, which are highly specific for this disease.
      The differences with Gaucher's disease and the pathomechanism of
      neuropathological damage are discussed.

PMID- 9595849
TI  - Obstructive sleep apnea syndrome in patient with Creutzfeldt-Jakob disease.
      Clinical and morphological report.
AB  - We report a case of Creutzfeldt-Jakob disease (CJD) which at the beginning of the
      disease presented clinical syndrome of progressive supranuclear palsy. Rapid
      intellectual deterioration, supranuclear palsy, postural instability and
      myoclonic jerks suggested clinical diagnosis of CJD. After five months suffering
      from the disease patient developed obstructive sleep apnea syndrome (OSAS)
      confirmed by serial polysomnograms. OSAS is discussed in the context of the
      localization of histopathological findings and possible involvement of central
      autonomic structures. The main structures affected by spongiosis and astrogliosis
      were cortex, thalamus, basal ganglia and midbrain. OSAS was found as another
      sleep disturbance in CJD apart from insomnia and sleep-wake cycle abnormalities.

PMID- 9595851
TI  - Ultrastructural studies of PECAM-1/CD31 expression in the developing mouse blood
      brain barrier with the application of a pre-embedding technique.
AB  - The aim of this study was to investigate the time of expression of the adhesion
      molecule platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in the
      developing mouse blood-brain barrier (BBB). Ultrastructural studies employing a
      preembedding technique described herein demonstrate that PECAM-1 is initially
      expressed on the luminal and abluminal endothelial cell surfaces in the newborn
      animals. This adhesion molecule expression appears to increase in intensity at 7
      10 days post partum and then decreases to a weak labelling of the luminal
      endothelial cell surfaces at two weeks after birth. Our results present
      immunocytochemical detection of active angiogenesis during early brain
      development in the mouse. Moreover, because of the important role that adhesion
      molecules play in immune responses in the central nervous system, upregulation of
      PECAM-1 prior to structural maturity of the BBB may suggest that the development
      of an "immune BBB" manifests prior to anatomical closure of the BBB in the mouse.

PMID- 9595852
TI  - Endothelial nitric oxide synthase in vascular endothelium of rat hippocampus
      after ischemia: evidence and significance.
AB  - Electron microscopy immunocytochemical study was performed to clarify
      ultrastructural localization and role of endothelial nitric oxide synthase (EC
      NOS) in the endothelial cells (EC) of rat hippocampal vessels after transient
      cerebral ischemia. EC-NOS immunoreactivity was found in the endothelial cells in
      association with plasma membrane, sub-plasmalemmal vesicles, basal membrane and
      in cytosol (cytoplasm free of subcellular organelles). A sharp transient increase
      in immunoreactivity of NOS was observed at 10 min up to 1 hour after ischemia.
      The results of the present study indicate that NO, as a potent vasodilator, may
      play a protective role in ischemic brain damage.

PMID- 9595853
TI  - Subependymal giant cell astrocytoma: clinical, histologic and immunohistochemical
      characteristic of 3 cases.
AB  - Three cases of subependymal giant cell astrocytoma (SEGA) in the women aged 23,
      26, and 36 years were reported. Two of them had no clinical evidence of tuberous
      sclerosis complex (TSC) and the one woman presented apparent mental retardation.
      All patients manifested sudden clinical onset with symptoms of elevated
      intracranial pressure due to tumor of lateral ventricles and obstructive
      hydrocephalus. At surgery, the neoplasm was removed totally in one case and
      resected partially in 2 cases. Histologically, the tumors were composed of large
      polygonal cells with vesicular nuclei, prominent nucleoli and glassy eosinophilic
      cytoplasm, intermingled with spindle and small cells. In addition, multinucleated
      and bizarre giant cells were present, but they were very numerous in one case
      only. The tumor cells revealed in all cases variegated immunoreactivity for glial
      fibrillary acidic protein (GFAP), S-100 protein, vimentin (VIM) and neuron
      specific enolase (NSE), with stronger expression of VIM than GFAP in 2 cases.
      Immunostaining of neurofilament proteins and synaptophysin was negative. The
      results suggest rather astroglial incomplete or aberrant differentiation and
      maturation than neuronal differentiation of tumor cells. The immunohistochemical
      variations of SEGA in asymptomatic TSC cases and those associated with tuberous
      sclerosis are discussed.

PMID- 9595854
TI  - Metaplastic meningioma with lipomatous changes.
AB  - We report here relatively rare lipomatous metaplastic changes, probably related
      to a prolonged clinical course, in not otherwise specified transitional
      meningioma. This lesion appears to have evolved over 30 years, with the initial
      diagnosis of multiple sclerosis. Histologically, it was composed of clusters and
      whorls of polygonal and spindle cells characteristic for transitional meningioma,
      with large areas of cells with lipid cytoplasmic accumulation, closely resembling
      mature adipocytes. The lipidization of other brain tumors and the histogenesis of
      these lesions in meningiomas on the background of meningeal embryogenesis are
      also discussed.

PMID- 9595855
TI  - Lead as an inductor of changes in the citrate transport to rat brain synaptic
      mitochondria.
AB  - The aim of the experiments presented here was to discern whether prolonged
      consumption of leaden water, that imitates environmental exposure, affects
      citrate transport to synaptic mitochondria. Our results indicate that during
      chronic lead intoxication both the velocity and the affinity of citrate transport
      to synaptic mitochondria decreased affecting the operation of Krebs cycle and
      consequently energetic processes in these mitochondria.

PMID- 9595856
TI  - Composition of the cerebral white matter sterol ester fraction in severe
      experimental hypoxia.
AB  - Severe hypoxia was induced in adult Wistar rats by means of exposure to an
      atmosphere containing 2.0 kPa of oxygen for a period of 3 minutes. The animals
      were sacrificed at 4 different periods following the hypoxia incident: 4 and 24
      hours, 14 days and 2 months, respectively, and sterol esters (ES) were isolated
      from the myelin fraction of the cerebral white matter. After hydrolysis, the
      isolated sterols were fed into a GC-MS system (gas chromatography-mass
      spectrometry). The following sterols were identified in the hydrolysates:
      cholesterol, cholesta-3,5-dien, cholesta-4-en-3-on, 22-propyl-3 beta-hydroxy-5,24
      cholestadien. The induced severe hypoxia lead to a twofold increase of the SE
      content in the myelin fraction of experimental rats (24 hrs, 14 days and 2 months
      samples). Cholesterol was the dominating sterol species in this fraction, however
      other minor sterols were found as well. The dynamic equilibrium between free and
      esterified sterols in the brain is controlled by the activity of respective
      sterol ester hydrolases. Esterification of free sterols renders them inaccessible
      for other metabolic changes, such as demethylation, reduction, isomerisation of
      double bonds, hydroxylation, and thus may lead to compositional changes of the
      myelin sterol spectrum under conditions of severe hypoxia.

PMID- 9595857
TI  - Gamma/delta T cell receptor genes rearrangement in the blood and brain of
      multiple sclerosis patients. A preliminary study.
AB  - The characterization of TCR gamma/delta gene diversity in peripheral blood
      lymphocytes and in cerebral white matter of MS patients was performed. In
      overwhelming majority of MS cases the V delta-J delta junctional repertoire was
      restricted as evidenced by oligoclonal rearrangements concerning V delta 1-J
      delta 1, V delta 2-J delta 1, V delta 3-J delta 1, V delta 5-J delta 1. The
      obtained results indicate, that the restricted pattern of TCR gene rearrangement
      may suggest oligoclonal expansion of certain clones of gamma/delta T cells that
      may be involved in recognition of putative autoantigen, significant in the
      etiopathogenesis of MS. The very striking positive correlation between monoclonal
      pattern of V delta-J delta rearrangement in peripheral blood and cerebral white
      matter of MS patients indicate that the gamma/delta T lymphocytes play
      significant role in MS pathogenesis.

PMID- 9595858
TI  - Parvalbumin immunoreactivity changes in the thalamic reticular nucleus during the
      maturation of the rat's brain.
AB  - The thalamic reticular nucleus (Rt) is a thin lamina of cells, through which
      thalamocortical and corticothalamic fibers pass. It is interposed between the
      thalamic nuclei and the internal capsule and it is composed of GABA-ergic cells
      with synapses that receive impulses from both kinds of fibers. Rt takes part in
      the negative feed-back system of controlling the information transfer from the
      thalamus to the cerebral cortex and it is focused in the sleep-waking cycle. The
      pattern of parvalbumin reactivity during maturation of Rt becomes the main aim of
      our study. The study was performed on 36 rats on various postnatal days (P0, P1,
      P2, P4, P5, P7, P10, P14, P17, P21, P30 and P90). The animals were anesthetized,
      transcardially perfused, cut on cryostat into 30-microns-thick frontal sections,
      stained immunocytochemically using standard ABC method and a mouse monoclonal
      antibody against parvalbumin. A small amount of round and oval, parvalbumin
      immunopositive cells was detected at stage PO, predominantly in the intermediate
      part of Rt, whereas the cells in ventral and lateral part at the same time were
      only slightly immunopositive. At P10 the cells in the intermediate part became
      more fusiform or oval because of the appearance of dendrites. At P14 we were able
      to observe separate, punctuated structures interpreted as the axonal endings.
      There were plenty of them at the time of full maturation of the intermediate
      portion of reticular nucleus (stage P21). At this time, the dorsal and ventral
      parts had their first synapses, too, but their maturation ended a week later. At
      P30 multipolar neurons, with round and fusiform somata were distributed
      relatively homogeneously throughout Rt. We compared the stage with the
      parvalbumin reactivity of the adult rat and found no difference in the
      morphological pattern of PV neurons.

PMID- 9595859
TI  - The pattern of synaptophysin changes during the maturation of the amygdaloid body
      and hippocampal hilus in the rat.
AB  - Synaptophysin is an integral membrane protein associated with small, electron
      lucent synaptic vesicles. Immunohistochemistry for this protein is a sensitive
      method to study subtle changes in synaptic density and distribution in various
      brain regions. In the present study, the synaptogenesis was examined in the rat
      basolateral amygdala in comparison with the hippocampal hilus, from the day of
      birth to adulthood. A total of 41 brains at various ages starting from P0 to P90
      (P--postnatal day) were examined. After perfusional fixation the brains were
      frozen and cut in the coronal plane and stained either with cresyl violet or
      standard immunohistochemical methods using the anti-synaptophysin antibody.
      Synaptophysin positive granules appeared just after birth in both structures, but
      their number was very low (about 0.28 x 10(6) and 0.13 x 10(6) per mm3 in the
      amygdala and hippocampus, respectively). In the basolateral amygdala the number
      of synapses increased rapidly reaching the maximum at P14 (1.6 x 10(6) per mm3)
      followed by about 45% decrease in number up to P30 and later being stabile. In
      the hippocampus two increases of the synaptogenesis were observed. The first at
      P7 (about 1.7 x 10(6) of synapses per 1 mm3) which was followed by dramatic
      decrease up to 0.7 x 10(6) per mm3 at P14. The second increase appeared later
      (about P90) and reached 1.7 x 10(6) per mm3. After that time the density of
      synapses was stabile. It may be supposed that the first characteristic wave of
      synaptogenesis observed in the hippocampus and amygdaloid body is due to the
      overproduction of synapses observed at that time in other cortical regions. The
      late wave of synaptogenesis found in the hippocampus is related to the great
      plasticity of the interneuronal connections in this period of development.

PMID- 9595860
TI  - Changes in localization of chosen lectins in gerbil's brain submitted to 3 and 4
      minute-long CNS ischemia.
AB  - The gerbils brains after 3- and 4-minute-long ischemia caused by bilateral common
      carotid artery occlusion and 14 days survival were investigated using lectin
      techniques. Chosen lectins, represented by synthetic plant glycoproteids, which
      are specifically bound to particular sugar residues (receptors) located on the
      cell surfaces were examined. Lectins recognizing the following sugar residues
      have been used in our experiment: 1. N-acetyl-D-galactosyl (using Helix pomatia
      agg., HPA) 2. alpha-D-mannosyl and alpha-D-glucosyl (using Concanavalin A, Con
      A). 3. beta-D-galactosyl (using Ricinus communis agg., RCA-120). 4. beta-D
      galactosyl and neuraminic acid (using Arachis hypogaea-Peanut agg., PNA). 5. N
      acetyl-galactosaminyl and N-acetyl-neuraminic acid (using Wheat germ agg., WGA).
      Changes in the glycoconjugates localization were found in neurons, glial cells,
      vessels, white matter fibers or neuropil. They were expressed by the weaking of
      the reaction with HPA in the hippocampus and white matter comparing to control.
      Con A receptors were considerably less susceptible to ischemia, though appearance
      of positively stained glial cells not found in the control group has been
      observed. Reaction with RCA-120 localized selectively in the network of capillary
      vessels decreased considerably. Similarly, receptors marked using PNA revealed
      reduction of staining reaction in white matter as well as in hippocampal
      interneurons. Using WGA we have also observed that staining reaction was reduced
      in capillary as well as in neuropil. That lectin indicated additionally strong
      accumulation of its sugar residues in glial cells appearing as a result of
      ischemia in particular sectors of hippocampus. The same cells were also Con A
      positive. The presented results indicate functionally and histochemically
      perceptible changes taking place in particular CNS elements as a result of short
      ischemia, expressed by the disturbances in the localization and accumulation of
      specific sugar residues examined with the use of lectin technique.

PMID- 9595861
TI  - Screening for presenilin-1 gene mutations by PCR-SSCP analysis in patients with
      early-onset Alzheimer's disease.
AB  - The majority of early-onset familial Alzheimer's disease (EOAD) has been
      associated with mutations in a novel gene on chromosome 14 which has been termed
      presenilin-1 gene. We screened for mutations within the presenilin-1 gene in
      twenty patients with EOAD using a PCR-SSCP analysis. We found three aberrant
      (mutant?) band patterns for exons 4 and 7 in three unrelated patients.

PMID- 9595862
TI  - Central nervous system involvement in pregnant rabbits with experimental model of
      antiphospholipid syndrome.
AB  - A postmortem neuropathological investigations were carried out on 23 female
      rabbits divided into 3 groups; pregnant animals with experimental
      antiphospholipid syndrome (APS), nonpregnant rabbits with antiphospholipid
      syndrome and nonpregnant animals without antiphospholipid syndrome. The aim of
      study was to analyze the CNS changes related to experimental model of APS in
      rabbits and to answer, whether pregnancy influences the intensity of CNS changes
      related to APS. The findings suggest that the experimental model of APS used in
      our study appeared to be effective in the development of the CNS involvement in
      rabbits. The extent thickening of CNS vessel wall is the most common feature of
      vasculopathy related to APS. In rabbits, pregnancy seems to be a factor
      facilitating the CNS damage related to APS.

PMID- 9595863
TI  - Desmoplastic cerebral astrocytoma of infancy: a case report.
AB  - We report a case of desmoplastic cerebral astrocytoma of infancy (DCAI), in a 7
      month-old boy. DCAI belongs to a group of recently described central nervous
      system (CNS) tumors, which also includes desmoplastic infantile ganglioglioma
      (DIG), pleomorphic xanthoastrocytoma (PXA) and dysembryoplastic neuroepithelial
      tumor (DNT), all characterized by relatively favorable prognosis and occurring
      mostly in children and young adults. DCAI is a rare neoplasm arising in the
      cerebral hemispheres within the first two years of life, and histologically is
      characterized by dense fibrous desmoplasia. In our case, CT scan presents a
      massive partially cystic tumor of the left cerebral hemisphere with an
      enlargement of the ventricular system. Histologically, the tumor was composed of
      cells arranged in fascicles and whorls forming storiform pattern.
      Immunohistochemical stainings for glial fibrillary acidic protein proved glial
      histogenesis of this tumor, while no cells were unequivocally immunopositive for
      neuron specific enolase, neurofilament proteins and synaptophysin what excludes a
      diagnosis of DIG--a similar entity but containing also a neuronal elements. Our
      studies, comprising a complete clinical, radiological, histopathological and
      immunohistochemical data, correspond to a cases of DCAI published before and it
      is the first one described in Poland.

PMID- 9595864
TI  - Tumor necrosis factor-alpha induced pathology in the rat brain: characterization
      of stereotaxic injection model.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a cytokine of cytotoxic and
      proinflammatory properties. It is believed to play an important role in
      inflammatory and demyelinization processes in the central nervous system (CNS).
      The aim of this study was to investigate what pathological changes could be
      produced by a stereotaxic administration of TNF-alpha in vivo into rat brain.
      Specimens were evaluated after staining with hematoxylin and eosin (H & E),
      Kluver-Barrera staining and using immunocytochemical methods. Disturbances of the
      blood-brain barrier (BBB) were analyzed as well as inflammatory infiltrates,
      changes in neurons, astrocytes and myelin. TNF-alpha injected in vivo into a rat
      brain caused a prominent inflammatory reaction in the cerebral meninges and a
      local cytotoxic brain edema when compared with the control group. Moreover,
      disturbances of the BBB premeability, infiltration of blood-borne macrophages in
      the area of the cytokine injection and early arising astrogliosis were observed.
      These results suggest that TNF-alpha can be an important mediator of inflammatory
      processes in the CNS.

PMID- 9595865
TI  - Practicability and acceptance of subcutaneous self-administration of the
      selective serotonin agonist sumatriptan.
AB  - To cater to the special situation of much reduced oral bioavailability which
      occurs in severe migraine attacks with pronounced nausea and vomiting,
      sumatriptan can also be used in a subcutaneous form that can be self
      administered. The aim of this study was to analyze the practicability and
      acceptance of a method of self-administration ("Glaxo-Pen") for treatment of
      severe migraine attacks by subcutaneous injection of sumatriptan. The Glaxo-Pen
      was compared with the conventional autoinjector for subcutaneous administration
      of sumatriptan. The multicenter study was conducted under practical conditions by
      150 office-based physicians in Germany. Patients who commonly suffered from
      severe migraine attacks were given a careful explanation of how to use the device
      ("Glaxo-Pen") for self-administration of subcutaneous sumatriptan and were able
      to practice using it under guidance. They were given a Glaxo-Pen with two
      sumatriptan refills to take with them for treating their own migraine attacks.
      The patients used a headache diary to document administration outside the
      practice session. A total of 376 patients were included in the study. The major
      findings were that 80% of the patients rated the Glaxo-Pen "very easy" or "easy"
      to use, and only 6.4% rated it "difficult" or "very difficult." Compared with the
      conventional autoinjector, the Glaxo-Pen was rated "much better" or "better" by
      77.9% of patients. Only 8.5% considered the Glaxo-Pen "worse" or "much worse"
      than the conventional autoinjector. The figures show that the great majority of
      patients found it easy to use sumatriptan for treating severe migraine attacks by
      self-administration under practical conditions. Thus, especially for patients who
      suffer from severe nausea, vomiting, or diarrhea during migraine attacks, this
      method of delivery is an easily used means of arresting migraine attacks.

PMID- 9595866
TI  - Serotonergic, catecholaminergic, and cardiovascular reactions to mental stress in
      female migraine patients. A controlled study.
AB  - This study aimed at the combined assessment of the serotonergic and sympathetic
      nervous system reactions of migraine patients before, during, and after the
      induction of mental stress in order to detect the possible role of these
      reactions in inducing a migraine attack. The responses to mental stress of the
      migraine patients were compared to a group of patients suffering from tension
      headache and a control group. Activation of the sympathoadrenomedullary system
      due to mental stress was successfully induced in the migraine patients (n = 23),
      in the tension headache patients (n = 18), and in the control group (n = 22). The
      results of this study present evidence of increased cardiovascular activity in
      migraine patients as compared to nonmigraineurs. However, no evidence was found
      of a specific serotonergic, sympathoadrenomedullary, or cerebrovascular response
      of migraine patients to mental stress as compared to nonmigraineurs.

PMID- 9595867
TI  - Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence.
      A placebo-controlled, outpatient study. Rizatriptan 022 Study Group.
AB  - Rizatriptan is a novel 5-HT1B/1D agonist which is rapidly absorbed after oral
      administration. The efficacy and tolerability of oral rizatriptan (5 mg and 10
      mg) were examined in this multicenter, double-blind, outpatient study of 1473
      migraineurs which featured randomized, placebo-controlled treatment of migraine
      recurrences. On experiencing moderate or severe migraine headaches, patients
      rated headache severity prior to dosing and at 30-minute intervals for 2 hours
      after dosing. Onset of effect was seen as early as 30 minutes after dosing with
      rizatriptan 10 mg. At 2 hours postdose, the percentage of patients with pain
      relief was significantly higher after rizatriptan 5 mg (62%) or 10 mg (71%)
      compared with placebo (35%). Complete relief was also significantly higher after
      rizatriptan 5 mg (33%) and 10 mg (42%) compared with placebo (10%). In patients
      experiencing headache recurrence after initial benefit, further relief was
      obtained in 71% with rizatriptan 5 mg (placebo 54%) and in 82% with rizatriptan
      10 mg (placebo 44%). Complete relief of recurrent headache was obtained in 36%
      with rizatriptan 5 mg, 49% with rizatriptan 10 mg, and 15% with placebo (P <
      0.05). The most common drug-related adverse experiences were dizziness,
      somnolence, asthenia/fatigue, and nausea (the incidences of which were low and
      dose related). There was no increase in the incidence of adverse experiences
      after use of up to three doses of rizatriptan within 24 hours. We conclude that
      both doses of rizatriptan are effective and well tolerated in the acute treatment
      of migraine and migraine recurrence, with the 10-mg dose preferred as it is more
      effective with a faster onset of action.

PMID- 9595868
TI  - 5-HT1B receptor polymorphism and clinical response to sumatriptan.
AB  - The 5-HT1 receptor agonist, sumatriptan, is highly effective in the treatment of
      migraine. Some patients, however, do not respond or experience recurrence of the
      headache. In addition, some patients report chest symptoms after sumatriptan. We
      investigated whether these different responses could be attributed to genetic
      diversity of the 5-HT1B receptor, which most likely mediates the therapeutic
      action and the coronary side effects of sumatriptan. Allele frequencies of two
      polymorphisms in the 5-HT1B receptor gene (G861C and T-261G) were investigated in
      migraine patients with consistently good response to sumatriptan (n = 14), with
      no response (n = 12), with recurrence of the headache (n = 12), with chest
      symptoms (n = 13), and in patients without chest symptoms (n = 27). Allele
      frequencies (G:0.74; C:0.26 at nt 861 and T:0.39; G:0.61 at nt -261) did not
      differ between patient groups, indicating that genetic diversity of the 5-HT1B
      receptor does not seem to be involved in the different clinical responses to
      sumatriptan.

PMID- 9595869
TI  - Psychological well-being in older adults suffering from chronic headache.
AB  - OBJECTIVE: The aim of this study was to examine two components of psychological
      well-being--life satisfaction and affective well-being--in community-dwelling
      elderly with (n = 321) and without chronic headache (n = 4955). METHODS: A
      checklist of chronic medical conditions was used to determine whether respondents
      were suffering from headache. Cantril's ladder was employed to measure life
      satisfaction. The subscale, Mental Health, from the MOS SF-20 was used to assess
      affective well-being. RESULTS: Headache sufferers reported lower life
      satisfaction as well as lower affective well-being. However, the difference in
      life satisfaction between the two groups disappeared after controlling for
      comorbidity. The difference in affective well-being disappeared after controlling
      for neuroticism. CONCLUSIONS: Lower life satisfaction in patients with chronic
      headache is caused by more comorbid diseases in the headache group. Lower
      affective well-being in headache sufferers is due to higher levels of neuroticism
      in the headache group.

PMID- 9595870
TI  - Development and validation of the Migraine-Specific Quality of Life
      Questionnaire.
AB  - This paper describes the development and validation of a migraine-specific
      quality-of-life instrument that is capable of measuring health-related quality-of
      life impairments attributed to migraine. Item selection, item reduction, and
      pretesting and finalization of items during the instrument development phase
      resulted in a total of 16 questions which were incorporated into the Migraine
      Specific Quality of Life Questionnaire (Version 1:0) (1992 Glaxo Wellcome Inc).
      Three meaningful dimensions were hypothesized: Role Function-Restrictive, Role
      Function-Preventive, and Emotional Function. In the instrument validation phase,
      the Migraine-Specific Quality of Life Questionnaire was mailed to 1109 migraine
      patients, providing a response rate of 45% (n = 458). Initial psychometric
      evaluation of the questionnaire indicated that it possessed adequate reliability
      with Cronbach's alpha for the three dimensions ranging between 0.70 to 0.85. The
      Migraine-Specific Quality of Life Questionnaire possessed adequate content and
      criterion validity. All but three items satisfied the test of construct validity.
      In conclusion, the Migraine-Specific Quality of Life Questionnaire has acceptable
      psychometric properties and can be used to estimate the effect of migraine and
      its treatment on the patient's health-related quality of life.

PMID- 9595871
TI  - Melatonin-responsive headache in delayed sleep phase syndrome: preliminary
      observations.
AB  - The occurrence of headache and its change after treatment with melatonin 5 mg
      were studied in 30 patients with delayed sleep phase syndrome. The medication was
      taken 5 hours before the endogenous nocturnal plasma melatonin concentration had
      reached 10 pg/mL. Three women (aged 14, 14, and 23 years) suffered from chronic
      tension-type headache. Their headache disappeared within 2 weeks after the start
      of treatment with melatonin. One 54-year-old man suffered from disabling migraine
      attacks without aura, twice a week. After starting melatonin treatment, only
      three migraine attacks were reported in 12 months. Ever since his 40s, a 60-year
      old man complained of cluster headache episodes lasting about 2 months, twice a
      year. In the year since starting melatonin treatment, only one 5-day cluster
      episode occurred. Nocturnal melatonin secretion in the patients with delayed
      sleep phase syndrome and headache did not differ significantly from that in the
      patients with the sleep disorder but without headache. Melatonin may be helpful
      in patients with headache who are suffering from delayed sleep phase syndrome.
      Its effectiveness may be due to modification of vascular and nociceptive systems
      or to its chronobiological action which adjusts the patient's biological clock to
      his/her life-style.

PMID- 9595872
TI  - The distinctive headache of the occipital condyle syndrome: a report of four
      cases.
AB  - Four examples of occipital condyle syndrome, that is, unilateral occipital pain
      and ipsilateral tongue paralysis due to selective erosion of the occipital
      condyle, are reported. The four patients complained of a continuous, severe,
      unilateral, occipital pain which kept them with the head rotated to the side of
      the pain and held with their hands. The pain became unbearable with head rotation
      to the nonpainful side and with unilateral suboccipital palpation. The onset of
      this very characteristic unilateral headache antedated by as long as 2 1/2 months
      the ipsilateral hypoglossal paralysis. The occipital condyle syndrome may be the
      first manifestation of cancer or of chronic inflammatory lesions; recognition of
      this distinctive headache enables the clinical diagnosis to be made.

PMID- 9595873
TI  - The Internet and migraine: headache resources for patients and physicians.
AB  - The Internet enables distribution of headache-related resources to patients and
      physicians in a manner never before possible. While these opportunities for
      communication and education open many doors to an increased awareness of
      migraine, there are also dangers in the free flow of non-peer-reviewed
      information on the Internet. The practicing physician or headache specialist
      needs to be aware of what headache-related resources are available on the
      Internet, both to recommend information to patients and to know what false
      information is being spread to headache sufferers. The purpose of this article is
      twofold: (1) to outline the types of headache-related information available on
      the Internet, including actual examples that the astute physician can view as
      time permits, and (2) to present examples of how such information can be biased,
      inaccurate, and potentially problematic for the curious patient or physician.

PMID- 9595874
TI  - Unilateral exertional headache as a symptom of cardiac ischemia.
AB  - A 62-year-old man developed right frontal headache after mild exercise, relieved
      promptly by rest. Treadmill exercise (stress testing) demonstrated ST depression
      on the electrocardiogram as the headache appeared. The exertional headaches were
      cured by coronary bypass surgery. Possible mechanisms for this unusual pain
      referral pattern are discussed.

PMID- 9595876
TI  - Leao's cortical spreading depression and the somatosensory homunculus: a
      contradiction?

PMID- 9595875
TI  - Successful treatment of headache related to intravenous immunoglobulin with
      antimigraine medications.
AB  - In order to investigate headache related to intravenous immunoglobulin, we
      studied a 36-year-old woman with a history of migraine receiving weekly
      intravenous immunoglobulin for refractory myasthenia gravis who experienced
      severe headaches with each treatment. Neurological examination, CT scan of the
      head, and a lumber puncture after the first headache were normal. Significant
      therapeutic response was based upon 50% reduction in pain and associated
      features. Headache features included throbbing pain which worsened with head
      movement and was associated with severe photophobia and nausea. Sumatriptan, 6 mg
      subcutaneous, reduced headache significantly with resolution of associated
      complaints. Treatment prior to intravenous immunoglobulin with dihydroergotamine
      mesylate resulted in development of only a mild dull ache without further
      development of severe head pain. Dihydroergotamine mesylate was also abortive in
      the few instances when the headache worsened. Headaches associated with
      intravenous immunoglobulin may have features of migraine and may be successfully
      prevented and/or treated with 5-HT1D receptor agonists.

PMID- 9595877
TI  - Syndrome of headache with neurological deficits and CSF lymphocytosis: a
      spreading depression mechanism? The role of SPECT.

PMID- 9595878
TI  - The ecology of outcomes: system accountability in children's mental health.
AB  - This article provides a conceptual and practical framework called the Ecology of
      Outcomes. Based on this framework, agencies that serve children and families
      build and use outcome-oriented information systems to respond to their clients in
      a more flexible manner. The goal is to improve promising programs by involving
      stakeholders in outcome identification and in utilization of results. Problems
      addressed include the emphasis human services place on rules compliance, lack of
      feedback to program staff to allow for midcourse correction, and lack of input by
      key stakeholders in the identification of outcomes to be measured. The following
      components of the framework are described: principles of outcome accountability,
      prerequisites and building blocks, implementing an outcome information system,
      and utilizing the results. Key elements of the framework are the integration of
      outcome information into a service system's decision-making process and the
      inclusion of client, stakeholder, and provider satisfaction information.

PMID- 9595879
TI  - A multistakeholder-driven model for developing an outcome management system.
AB  - Increasing demands for accountability in the delivery of public mental health
      services are engendering organized systems of treatment outcome monitoring. As
      such systems are designed and implemented, it is critical that key stakeholders
      be involved to the greatest extent possible in developing assessment instruments
      and methodologies so as to ensure relevance and acceptability of the outcome
      management system. A multistakeholder-based initiative for developing
      standardized outcome assessment for public mental health services in Virginia is
      described. Key components of the initiative include the process by which
      stakeholders were enlisted, the identification of recommended assessment
      instruments, and a pilot project that began the evaluation of the feasibility,
      utility, and cost-benefit of using the instruments. To illustrate features of
      this initiative, the child/adolescent mental health pilot project is described in
      detail. Implications for behavioral health administrators and next steps for
      Virginia's outcome management system are discussed, highlighting the role of key
      stakeholders.

PMID- 9595880
TI  - Multiagency outcome evaluation of children's services: a case study.
AB  - Outcome monitoring has become a focus of accountability for public and nonprofit
      human service agencies. Besides providing answers to funders' questions about the
      services' impact, outcome monitoring helps administrators improve program
      effectiveness. After a three-year development period and a one-year
      implementation experience, SumOne for Kids represents a technically advanced
      outcome-monitoring system for children's mental health and/or child welfare
      services. Initiated, designed, and tested by 31 children's service agencies
      throughout Pennsylvania, and with state bureaucrats' and policy makers'
      encouragement, SumOne for Kids represents an effort to create a bottom-up/top
      down process for implementing a statewide outcome-monitoring system. This article
      describes the genesis of this outcome-monitoring system, primary design
      principles, use of social validation for outcome selection, resolution of
      methodological difficulties, and reasons for selecting functional over clinical
      outcomes. The article reviews lessons learned through the development experience
      instructive to children's service managers, program evaluators, and industry
      leaders interested in establishing outcome-monitoring systems.

PMID- 9595881
TI  - Managing what you measure: creating outcome-driven systems of care for youth with
      serious emotional disturbances.
AB  - This article presents the California System of Care Model for youth with severe
      emotional disturbances as an illustration of how ongoing assessment of the costs
      and outcomes of service delivery can be an integral part of a service delivery
      model. The core of this model, developed initially in Ventura County, California,
      is a five-step planning process that guides care system development and
      implementation. The implications of each stage of the planning process for
      evaluation and feedback at the child, family, and system levels are highlighted.
      A set of principles for selecting outcome measures deriving from the planning
      process are also presented that, in conjunction with the planning model, serve as
      guidelines for establishing outcome measures within care systems. The resulting
      specific plan for measuring system- and client-level outcomes deriving from this
      process, along with challenges to the implementation of the outcome management
      plan, is described.

PMID- 9595882
TI  - The development of a statewide continuous evaluation system for the Texas
      Children's Mental Health Plan: a total quality management approach.
AB  - The article presents a description of processes involved in developing and
      implementing a statewide continuous evaluation system for the Texas Children's
      Mental Health Plan (TCMHP) and quality management tools used to approach
      implementation challenges. Implementation issues are discussed relating to
      stakeholder involvement, evaluation design evolution, measurement method
      modification, evaluation integration, staff training, data quality control,
      communication of results, and use of results in decision making. A review of
      implementation processes suggests evaluation design and activities should be seen
      as constantly evolving in response to ongoing stakeholder input. Involving
      stakeholders in design and implementation can result in increased data quality,
      data-informed decision making to improve service delivery, and increased public
      accountability. The TCMHP evaluation system development demonstrates that quality
      management tools can provide a useful framework to work through design and
      implementation problems, and a continuous evaluation system can provide an
      infrastructure for meeting data needs in a managed care environment.

PMID- 9595883
TI  - Program specification: a precursor to program monitoring and quality improvement.
      A case study from Boysville of Michigan.
AB  - As a result of new accreditation standards, diminishing resources, community
      concern with recidivism, and state agencies and foundations requiring more
      rigorous evaluations, program accountability is becoming a necessity for social
      services providers and contractors alike. In the subsequent discussion, Boysville
      of Michigan's program specification process is described; specifically, the ways
      in which the process has been useful for monitoring program operations,
      identifying quality improvement indicators, designing ongoing program
      evaluations, and developing consensus and continuity with respect to program
      theory and procedures. In addition, benefits, lessons learned, and implications
      for services delivery are discussed.

PMID- 9595884
TI  - Managing care across systems to improve outcomes for families and communities.
AB  - Behavioral health administrators deserve much credit for their efforts to
      integrate services for children with serious emotional disturbances and to
      instill a concern for efficiency through the concept of managed care. Recent
      changes in federal policy signal the next stage of development in systems of
      care. Issues of accountability now are shifting toward comprehensive systems of
      care and improving outcomes for families and communities, not just individuals.
      As they help build such systems in their states and communities, behavioral
      health administrators can help their colleagues in other systems understand the
      potential usefulness of concepts and practices associated with managed care and
      the broader notion of a system of care. In turn, they will be asked to expand
      their conception of the accountability of the mental health agency for the
      outcomes being experienced by families, neighborhoods, and the community as a
      whole.

PMID- 9595886
TI  - From many into one: addressing the crisis of quality in managed behavioral health
      care at the millennium.

PMID- 9595885
TI  - Outcomes and accountability from a family perspective.

PMID- 9595887
TI  - Why psychopharmacological researchers need to become more vocal and thoughtful in
      debating issues in research ethics.

PMID- 9595888
TI  - Risk in research--from the Nuremberg Code to the tri-council code: implications
      for clinical trials of psychotropic drugs.

PMID- 9595889
TI  - In vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by
      sertindole in the rat brain.
AB  - OBJECTIVE: To determine the in vivo occupation of dopamine D1, D2 and serotonin
      (5-HT)2A receptors by novel antipsychotic agent sertindole using N-ethoxycarbonyl
      2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible antagonist at these
      receptor sites. DESIGN: Animal study. INTERVENTIONS: Intraperitoneal
      administration to Wistar rats of 1 of 4 test compounds: a control compound of
      0.15% tartaric acid, or a compound of either sertindole (0.5 mg/kg or 2.0 mg/kg)
      or clozapine (20 mg/kg) dissolved in 0.15% tartaric acid 1 hour before
      intraperitoneal administration of EEDQ (8 mg/kg) or ethanol/water solution.
      RESULTS: Sertindole exhibited little or no effect on D1 and D2 binding sites in
      vivo. On the other hand, sertindole occupied 5-HT2A receptors more extensively
      and firmly than EEDQ. This study indicates that sertindole is characterized by
      high occupancy of 5-HT2A receptors and by low or minimum occupancy of D1 and D2
      receptors. CONCLUSIONS: These characteristics are very similar to atypical
      antipsychotic agents such as clozapine. Sertindole's low liability to cause
      extrapyramidal side effects (EPS) may be related to greater long-term binding for
      5-HT2A receptors relative to D2 receptors.

PMID- 9595890
TI  - Olfactory identification and Stroop interference converge in schizophrenia.
AB  - OBJECTIVE: To test the discriminant validity of a model predicting a dissociation
      between measures of right and left frontal lobe function in people with
      schizophrenia. PARTICIPANTS: Twenty-one clinically stable outpatients with
      schizophrenia. INTERVENTIONS: Patients were administered the University of
      Pennsylvania Smell Identification Test (UPSIT), the Stroop Color-Word Test
      (Stroop), and the Positive and Negative Syndrome Scale (PANSS). OUTCOME MEASURES:
      Scores on these tests and relation among scores. RESULTS: There was a convergence
      of UPSII and Stroop interference scores consistent with a common cerebral basis
      for limitations in olfactory identification and inhibition of distraction. There
      was also a divergence of UPSIT and Stroop reading scores suggesting that the
      olfactory identification limitation is distinct from a general limitation of
      attention or a dysfunction of the left dorsolateral prefrontal cortex. Most
      notable was the 81% classification convergence between the UPSIT and Stroop
      incongruous colour naming scores compared with the near-random 57% classification
      convergence of the UPSIT and Stroop reading scores. CONCLUSIONS: These data are
      consistent with a right orbitofrontal dysfunction in a subgroup of patients with
      schizophrenia, although the involvement of mesial temporal structures in both
      tasks must be ruled out with further study. A multifactorial model depicting
      contributions from diverse cerebral structures is required to describe the
      pathophysiology of schizophrenia. Valid behavioural methods for classifying
      suspected subgroups of patients with particular cerebral dysfunction would be of
      value in the construction of this model.

PMID- 9595892
TI  - Paroxetine in a patient with obsessive-compulsive disorder, anorexia nervosa and
      schizotypal personality disorder.

PMID- 9595891
TI  - Effects of electroconvulsive therapy and desipramine on neuroendocrine responses
      to the clonidine challenge test.
AB  - OBJECTIVE: To investigate responses to the clonidine challenge test in
      depression, and after electroconvulsive therapy (ECT) or desipramine treatment
      for depression, in order to determine the usefulness of noradrenergic responses
      to clonidine as a state or trait marker in depression. PATIENTS: Twenty-six
      patients with depression and 15 control subjects. SETTING: The psychiatric ward
      of St. Joseph's Hospital in Hamilton. INTERVENTIONS: In the patients with
      depression: clonidine challenge pre- and post-treatment with ECT or desipramine.
      In the controls: 2 clonidine challenge tests 4 to 8 weeks apart. OUTCOME
      MEASURES: The primary measure was the growth hormone response to the clonidine
      challenge. Plasma norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG),
      cortisol, blood pressure, pulse and sedation levels were examined in subgroups of
      participants as secondary measures. RESULTS: The pre-treatment growth hormone
      response to clonidine was significantly more blunted in patients than in controls
      (p = 0.02). This response improved in both treatment groups after therapy and,
      although it remained decreased, there was no longer a significant difference in
      response between the patients and the controls. In the patients, a decreased
      growth hormone response to clonidine at baseline was correlated with response to
      treatment. Of the secondary measures, patient baseline norepinephrine levels were
      significantly elevated pre- and post-treatment, although there were no
      significant group-by-time challenge effects. MHPG levels were not significantly
      different pre- and post-treatment between patients and controls. Baseline blood
      pressure and pulse were elevated in the patients pre- and post-treatment. These
      differences were not statistically significant and did not change after
      treatment. Sedation levels were not significantly different among the groups at
      baseline. Clonidine-induced sedation occurred significantly earlier in the
      patients pretreatment and improved to the range of the controls after treatment.
      Pretreatment cortisol response was significantly more blunted in the patients who
      received ECT than in the controls; however, the group-by-time effect post
      treatment was no longer significant. DISCUSSION: Treatment with either
      desipramine or ECT modified noradrenergic functioning in patients with
      depression, as assessed by growth hormone response to the clonidine challenge. In
      the patients, a decreased growth hormone response at baseline was correlated with
      clinical response. Changes between pre- and post-treatment measures suggest that
      this challenge test may not be sensitive enough to serve as a trait marker but
      may correlate with the state of depression in a subpopulation of these patients.

PMID- 9595893
TI  - Depression and cardiovascular disorders.

PMID- 9595894
TI  - Venlafaxine drug-drug interactions in clinical practice.

PMID- 9595895
TI  - The health of women in need.

PMID- 9595896
TI  - Health issues of women in rural environments: an overview.
AB  - Significant attention has been devoted to the plight of rural residents and their
      health care systems in the past decade. The literature offers general information
      about rural environments, but little has been written about the many rural
      subgroups living across the 50 states. This article presents a profile of
      America's rural women and discusses the impact of economic, social, geographic,
      and cultural factors on their health. It is based on a review of the literature
      and the author's decades of personal and professional experiences in rural
      communities. The information can help physicians to better understand the medical
      concerns of the rural women they may encounter in their practices.

PMID- 9595897
TI  - Responding to the needs of low-income and homeless women who are survivors of
      family violence.
AB  - Americans have started to recognize interpersonal violence as a major health care
      issue. Increasingly, clinicians are beginning to recognize both the high rate of
      victimization among extremely poor women and its health consequences. However,
      most clinical responses focus on the immediate effects of child abuse, partner
      abuse, and rape. The long-term medical and mental health consequences and the
      relationship between early victimization and adult problems are still largely
      ignored. This article focuses on medical and mental health needs of extremely
      poor women survivors of interpersonal violence. It begins by documenting the
      extent and nature of violence against low-income women. Special attention is
      focused on the long-term sequelae of childhood abuse and on identifying and
      managing complex trauma responses in these women. The article concludes by
      discussing obstacles to care and the necessity of advocating for increased
      resources to respond to women living in extreme poverty.

PMID- 9595898
TI  - The "hidden patient": older relatives raising children orphaned by AIDS.
AB  - In the United States today, thousands of grandmothers and other third- and fourth
      generation relatives are raising children and adolescents whose primary parent,
      usually the mothers, has died from acquired immune deficiency syndrome (AIDS) or
      is too ill to serve as the primary parent. More than 100,000 children below the
      age of 18 are expected to lose their mothers to AIDS by the year 2000, most in
      poor communities. Isolated by the demands of caregiving, child care, and the
      stigma of AIDS on even uninfected family members, this group of older surrogate
      parents is at risk not only for chronic conditions and stress-related somatic
      complaints, but for neglected health. Using the gerontological concept of the
      "hidden patient," this article presents four cases drawn from an exploratory
      study of the physical and emotional health risks and health behaviors of older
      adults raising children orphaned by AIDS. External and internal barriers to self
      care are described, including lack of child and respite care and health
      insurance, caregiver depression, and denial of health problems.

PMID- 9595899
TI  - Promoting social cohesion to improve health.
AB  - The disintegration of communities places stress on the well-being of residents.
      This paper presents four case studies of efforts to strengthen community in four
      distinct US cities. They are based on interviews and observations made by the
      author, as well as on published accounts and reports in scientific and lay media.
      The case studies suggest that each community has a unique set of problems that
      require targeted interventions. The case studies suggest that interventions can
      promote social cohesion, thereby recreating the social foundation for good
      health. The implications for women's health are discussed.

PMID- 9595900
TI  - Sex work and health: a question of safety in the workplace.
AB  - Sex work is an occupation or trade involving exchange of sexual services for
      economic compensation. Although health problems associated with prostitution,
      such as sexually transmitted diseases and violence, are commonly assumed to be
      "risks of the trade," the illegality and stigma of prostitution have prevented
      the medical establishment from viewing it through the lens of occupational safety
      and health. They have also resulted in a failure to look at such day-to-day
      conditions and illnesses as repetitive stress injuries and other musculoskeletal
      problems, bladder infections, and work-related stress that may be of more
      immediate concern to sex workers. This paper reviews what is known about the
      safety and health hazards associated with prostitution through some formal
      research, but primarily through informal discussions with sex workers over two
      decades. The overarching factor affecting the health of sex workers is the legal
      context, thus that is reviewed first; then I look at occupational hazards and
      conclude with some suggestions for immediate action and further research.

PMID- 9595901
TI  - Women in New York City's Medicaid program: a report on satisfaction, access, and
      use.
AB  - This article analyzes the experiences of women in New York City's Medicaid
      program regarding their satisfaction with, access to, and use of medical care
      during an early phase of a managed care enrollment initiative. Data for this
      study are from a 1994 survey of New York City Medicaid beneficiaries (1,221
      women) as well as from focus group discussions. Differences in reported
      satisfaction levels, access, and use between managed care enrollees and
      conventional Medicaid beneficiaries are examined, as are differences between
      women in fair and poor health and those in excellent, very good, and good health.
      Multivariate analyses found that women enrolled in Medicaid managed care overall
      were significantly more likely to report greater satisfaction with access,
      interpersonal quality, technical skills, and arrangements for choosing a personal
      doctor; equivalent use; and better access compared to those in conventional
      Medicaid. Female managed care beneficiaries who reported worse health, however,
      were significantly more likely than those in better health to also report less
      satisfaction in 13 dimensions of medical care. Continued evaluation of Medicaid
      managed care is warranted, particularly as more vulnerable groups are enrolled.

PMID- 9595902
TI  - Linking women in jail to community services: factors associated with rearrest and
      retention of drug-using women following release from jail.
AB  - Women in jail experience high rates of many health and social problems. This
      study examined the effects of preexisting social and health characteristics and
      the type of services received on retention in community aftercare for 193 drug
      using women released from the New York City jail to two low-income communities.
      Rearrest rates for program participants were compared to a group of women not
      eligible for services because of their residence outside the target communities.
      Women who enrolled in residential programs with on-site drug treatment and other
      social services after release were compared to women who enrolled in less
      comprehensive services. The residential treatment group participated in the
      program significantly longer (276 v 180 days, p = .02) than women in other types
      of services. Women in residential programs were significantly more likely to have
      used crack or cocaine in the 30 days prior to arrest than women in other types of
      programs (84% v 59%, p = .001), but few other prior differences among the
      different treatment groups were noted. Therefore, differences in outcome are
      unlikely to be attributed to preexisting differences in risk profile. Women who
      participated in postrelease services were significantly less likely to be
      rearrested in the year after release than a comparable group of women who
      participated in jail services, but were not eligible for postrelease services
      (38% v 59%, p = .02).

PMID- 9595903
TI  - Immigrant women and the emergency department: the juncture with welfare and
      immigration reform.
AB  - This article discusses the Personal Responsibility and Work Opportunity
      Reconciliation Act and the Illegal Immigration Reform and Immigrant
      Responsibility Act and their potential impact on immigrant women's access to
      medical services. Current federal mandates assuring access to emergency medical
      services and new restrictions on financing of health care under federal programs
      such as Medicaid and Medicare would appear to be on a collision course. Both acts
      specifically reaffirm federal law on delivery of emergency services without
      addressing the financing of that care. Unfunded mandates in an era of diminished
      ability to shift costs onto insured patients are problematic for the institutions
      that provide uncompensated care. Specific protections for victims of domestic
      violence are also discussed.

PMID- 9595904
TI  - The prevalence of risk factors among women in the United States by race and age,
      1992-1994: opportunities for primary and secondary prevention.
AB  - OBJECTIVE: To analyze the prevalence of 11 modifiable behavioral risk factors,
      including multiple risk factors, among white, black, Asian and Pacific Islander,
      American Indian, and Hispanic women in the United States. DESIGN: We used
      Behavioral Risk Factor Surveillance System (BRFSS) data for 1992 to 1994 to
      examine risk factors (smoking; obesity; diabetes; heavy alcohol consumption;
      sedentary lifestyle; and inadequate use of seat belts, pap smears, consumption of
      fruits or vegetables, mammography and colorectal screening, and immunization),
      among women age 18 to 49, 50 to 64, and 65 and older. We also conducted a
      multiple regression analysis, comparing the odds of having either 1-2 versus 0 or
      3 or more versus 0 risk factors among racial/ethnic groups, controlling for
      education and family income, to see if racial/ethnic differences can be
      attributed to socioeconomic differences. RESULTS: US women engage in a variety of
      behaviors that place them at risk for many causes of morbidity and mortality.
      Risk profiles vary substantially among racial/ethnic populations: Pacific
      Islanders have relatively low prevalences of most major risk factors, while
      blacks and American Indians have relatively high prevalences of many major risk
      factors. Prevalence differences among racial/ethnic populations are diminished
      but not eliminated when socioeconomic factors are accounted for. CONCLUSIONS:
      Appropriately designed programs to help women reduce their behavioral risk
      factors are needed. Action by health care providers, communities, and policy
      makers can substantially improve the health of women in the United States.

PMID- 9595905
TI  - The FDA and women's health.

PMID- 9595906
TI  - Should nurses purchase their own professional liability insurance? Pro.

PMID- 9595907
TI  - Should nurses purchase their own professional liability insurance? Con.

PMID- 9595909
TI  - Thin line: managing care for adolescents with anorexia and bulimia.
AB  - Anorexia nervosa ranks third among common chronic disorders in adolescents,
      surpassed only by asthma and obesity. Unfortunately, recent changes in health
      care and insurance have resulted in fewer resources for these vulnerable clients
      Anorexia and bulimia are best managed by a treatment team, but frequently it is
      the nurse who manages much of the eating-disordered client's care, especially
      when there is no available team, or when the nurse is the primary care provider
      or therapist. Nurses can and do care for adolescents with anorexia and bulimia.
      All it takes is commitment, knowledge, and networking.

PMID- 9595908
TI  - A legal nightmare. Denver nurses indicted.

PMID- 9595910
TI  - Rituals of placenta disposal.

PMID- 9595912
TI  - Reflections from a neonatal nurse: a philosophical dialogue.

PMID- 9595911
TI  - Abuse among pregnant adolescents: differences by developmental age.
AB  - PURPOSE: The purpose of this study was to describe the incidence of abuse among
      pregnant teens in the three developmental stages of adolescence and to determine
      if abuse was related to pregnancy planning, high school participation, substance
      use during pregnancy, pregnancy complications, and infant birth weight. DESIGN:
      Prospective survey. METHODS: A total of 559 pregnant adolescents between the ages
      of 13 and 19 were interviewed. Abuse was measured by the Abuse Assessment Screen.
      Substance use was measured by self-report. Birth weights were obtained from
      hospital records. RESULTS: Abuse was reported by 37% of the adolescents. In every
      age group, the incidence of low birth weight was higher in those who had been
      abused. CLINICAL IMPLICATIONS: The high rates of abuse reported by both
      adolescent and adult women in this study emphasize the need for nurses in every
      setting to incorporate routine screening for abuse into their nursing
      assessments.

PMID- 9595913
TI  - The significance of power in research design (Part II).

PMID- 9595914
TI  - Pharmacokinetics in pregnant women and children.

PMID- 9595915
TI  - [Raloxifene: a new molecule for the prevention of menopausal osteoporosis].

PMID- 9595916
TI  - [Current status and prospectives of aromatase inhibitors in the treatment of
      advanced breast cancer].
AB  - Endocrine therapy represents one of the most effective instruments for the
      palliative and adjuvant treatment of breast cancer, in particular in
      postmenopausal patients. While tamoxifen still forms the treatment of choice
      during the adjuvant phase and the first-line treatment during the metastatic
      phase, aromatase inhibitors undoubtedly represent the treatment of choice for
      patients who do not respond to antiestrogen treatment. These drugs represent a
      heterogeneous family of compounds able to provide more or less selective
      inhibition of aromatases by forming an irreversible bond with the catalytic site
      of the enzymatic complex (type I inhibitors) or using a competitive mechanism
      (type II inhibitors). Among the type I drugs, 4-hydroxyandrostenedione and
      hexamestane are those that probably attract greatest clinical interest. These
      drugs can significantly reduce the circulating levels of estrone and estradiol,
      and have been shown to be active in 20% of patients pretreated with tamoxifen.
      Moreover, hexamestane was also effective in patients pretreated with type II
      inhibitors, of which the parent drug is aminoglutethimide. This drug is still
      used in the second and third-line treatment of breast cancer but, since it causes
      collateral effects in a substantial percentage of patients, above all when used
      at higher doses in combination with hydrocortisone, it will soon be replaced by
      second and third generation inhibitors, like letrozole, fadrozole, vorozole and
      anastrozole. These drugs have been shown to be significantly more active than
      aminoglutethimide, both in vitro and in vivo, and above all more selective. In
      particular, even at high doses anastrozole has not been found to interfere with
      steroidogenesis at a corticoadrenal level. Moreover, anastrozole has been shown
      to be very active even at relatively modest doses given in a single daily dose.
      Two recent controlled studies, including a total of over 600 patients, recently
      demonstrated that, if used in second line in patients who no longer responded to
      adjuvant or palliative tamoxifen therapy, anastrozole is just as effective but
      probably better tolerated than megestrol acetate. Studies are now in progress or
      are currently being launched to evaluate the possible value of anastrozole and
      other third generation inhibitors both as first-line treatment and as adjuvant
      treatment as an alternative or in combination with tamoxifen.

PMID- 9595917
TI  - [Treatment of intraepithelial cervical neoplasia with REP Radiosurgical Excision
      Procedure)].
AB  - Radiosurgical cervical excision has been performed in 59 patients affected by CIN
      of various stages. This non-traumatic method uses 3.8 MHz radio waves to cut
      and/or coagulate without postoperative pain and tissue destruction. The
      radiosurgical excision has been performed in local anesthesia by a loop electrode
      or microneedle according to the seat of the lesion. The therapy was "effective"
      in 98% of cases (58/59) whereas the "incomplete excision" of CIN was observed in
      6.7% (4/59). Complications (postoperative and late bleeding) occurred in 3.2% of
      the patients (2/59). Therefore, the Radiosurgical Excision Procedure (REP) can be
      considered an easy technique in ambulatory surgery; this method is effective in
      the treatment of CIN with either therapeutic and economic advantages and
      guarantee the functional and anatomic integrity of the cervix.

PMID- 9595918
TI  - [Tri-test: clinical considerations on 1784 cases].
AB  - BACKGROUND: To evaluate the triple screen serum test as a noninvasive screening
      test for expectant mothers > 35 years old, who are not usually considered for
      invasive screening for trisomy 21. METHODS: 1784 tri-tests (triple serum
      screening tests) were performed on expectant mothers between their 15th and 18th
      week of pregnancy, using the radioimmunological Ria-Kodak with an Alpha program
      (Logical Medical System LTD) with a cut-off value of 1:350. RESULTS: 244 positive
      equal to 13.60%. The percentage of false positives was respectively 12.9% (age <
      35) and 28% (age > 35). Only in two of these cases did we have a positive
      response in amniocentesis for a fetus affected with Down syndrome. Of the 1540
      patients with a negative tri-test, one woman gave birth to a fetus with Down
      syndrome. CONCLUSIONS: Our study revealed a sensitivity of 66%. The elevated
      number of false positives has led us to decide on a variation on the cut off in
      the future: from 1:350 to 1:300.

PMID- 9595919
TI  - [Psychosexual problems in menopause].
AB  - BACKGROUND: A case-control study about the evaluation of sexual disturbances
      during menopause considering the ways in which these are caused by neuro
      endocrine disequilibrium, or by a psycho-social crisis during menopause. In
      addition, there is an evaluation of the efficacy of hormonal replacement therapy
      on sexual disturbances. METHODS: Two groups of 44 menopausal women. The first
      group was transdermically treated with 50 micrograms/day of estradiol for three
      weeks in a one month period with the association of MAP 10 mg administered orally
      for 10 days. The other group received a placebo. Both groups were studied for a
      period of six months with quarterly check-ups. We have identified the crucial
      symptoms using a series of interviews which consisted of questions regarding the
      classic symptoms of menopause. The intensity of such symptoms was classified on a
      five point scale. Specific questions were asked regarding the frequency of sexual
      intercourses and the presence and intensity of sexual desire. The same questions
      were consecutively asked to the subjects at three month intervals. RESULTS: The
      presence of crucial symptoms was distributed as follows: hot flashes and
      perspiration in 65%, anxiety in 60%, symptoms of depression in 50%, paraesthesia
      and asthenia in 40%, insomnia in 35%, varying degrees of memory loss in 30%,
      vaginal dryness and dyspareunia in 15% of the subjects in both groups (control
      and sperimental). Sexual desire was diminished or very diminished in 48%,
      unchanged in 31% and increased in 11.5%. The frequency of sexual intercourse was
      diminished or very diminished in 56.5%, unchanged in 25% and absent in 18.5%. For
      the vasomotor disorders, patients participating in the first group demonstrated
      only a slight persistence in 15% by the end of six cycles. Similar results were
      found with symptoms of insomnia. Only 10% of the patients mentioned slight
      symptoms of anxiety or depression. All of the patients with vaginal dryness and
      dyspareunia showed a total remission of the symptoms. Subjects participating in
      the control group noted a slight increase in vasomotor disturbances, while
      psychological symptoms decreased slightly. Vaginal dryness and dyspareunia
      remained unchanged. At the end of treatment, only a modest percentage of the
      subjects, from both groups, mentioned an increase in the frequency of sexual
      desire and intercourse. CONCLUSIONS: These results shows that the lack of
      estradiol is not the most important factor in deciding sexual behavior. Also, for
      the group of patients complaining symptoms connected to vaginal atrophy, only a
      small increase in sexual interest and practice was verified once the normal
      trophism of tissue was reestablished. The same data obtained from the control
      group is probably a result of a certain mental condition caused by the
      "pharmacological effect".

PMID- 9595920
TI  - [Angiogenesis and endometrial carcinoma. Correlations with blood flow analysis by
      transvaginal color Doppler ultrasonography].
AB  - Neoangiogenesis is a basic event in the evolution and spread of several solid
      neoplasms. Angiogenesis is an active phenomenon in physiological endometrium in
      the reproductive age and seems to disappear in postmenopause. Endometrial
      hyperplasia and adenocarcinoma are associated with signs of angiogenetic
      activity. The factors promoting angiogenesis in endometrial carcinoma are still
      unknown. Similarly it is not possible to recognize which endometrial carcinoma is
      potentially angiogenetic, but a relationship between angiogenesis and early
      metastatic spread has been established. Angiogenesis is definitely a late
      component of invasive tumour, but an early angiogenetic behaviour of some
      neoplastic clones, that could be a main prognostic factor for endometrial
      carcinoma is hypothesized.

PMID- 9595921
TI  - [Differential diagnostic problems in metastatic ovarian tumors of intestinal
      origin. Description of a clinical case].
AB  - The authors report the case of a patient undergoing gynecological surgery to the
      presence of a right ovarian mass with a maximum of diameter of 23 cm which was
      found to be a secondary tumour. Histologically analysis showed that this mass was
      the metastasis of a tumour of intestinal origin, a finding that was then
      confirmed by flow cytometry. The authors draw attention to the need for patients
      with suspected ovarian tumour to undergo preoperative diagnostic tests to
      evaluate the possibility of neoplastic pathology in the gastrointestinal tract in
      order to optimise surgery and antiblastic treatment.

PMID- 9595922
TI  - [Postmenopausal endometrial tuberculosis. A clinical case].
AB  - Post-menopausal tuberculosis of the female genital tract is an uncommon condition
      that has received relatively little attention in the literature. The case
      described by the authors is about a sixty year old woman whose condition was
      brought to attention by leukorrhea and abnormal bleeding associated with a smear
      test suggesting CIN 1. An endometrial aspiration biopsy revealed necrotic debris
      with focal granulomata and numerous acid-fast bacilli. Fungal stains were
      negative while mycobacterium tuberculosis was found. After three months of
      combination antimycobacterial treatment, she underwent a total abdominal
      hysterectomy with bilateral salpingo-oophorectomy followed by six months of post
      operative drug therapy.

PMID- 9595923
TI  - [A case of atypical ectopic pregnancy].
AB  - The authors report the case of a 38-year-old woman who underwent total
      laparohysterectomy for multiple uterine leiomyomas and right adnexectomy
      following the intraoperative finding of a right tubal abortion.

PMID- 9595924
TI  - [Clinical efficacy of tamoxifen in the treatment of premenstrual mastodynia].
AB  - BACKGROUND: Premenstrual syndrome (PMS), which was first described by Frank in
      1931, is a clinical condition that is not easy to classify in terms of either
      symptoms or from a diagnostic and therapeutic point of view. AIMS: The aim of
      this study was to evaluate the efficacy of tamoxifen, an antiestrogen drug, using
      a double-blind study with placebo in the treatment of mastodynia, one of the most
      frequent symptoms of PMS, given that an absolute or relative increase in
      estrogens is one of the most controversial etiopathogenetic hypotheses. METHODS:
      The study included a group of 88 outpatients aged between 22 and 40 with regular
      menstrual cycles and intense mastodynia. Before commencing therapy, a detailed
      medical history was compiled for each subject and all underwent a gynecological
      and breast examination, hematochemical and instrumental tests (scan and
      mammography) in order to rule out other PMS-related organic pathologies. The
      patients were randomly divided into two groups of 44: one group received
      tamoxifen at a dose of 10 mg by mouth from day 5 to day 24 of the menstrual
      cycle, whilst a placebo was administered to the other group using the same dosage
      scheme. All women underwent a thorough control examination at the end of
      treatment and two months after the end of treatment. RESULTS: At the end of
      treatment 90% of patients reported a complete resolution of symptoms, whilst 10%
      only showed a slight improvement. In the control group, 86% showed a transitory
      reduction in symptoms and 13% did not report any improvement. CONCLUSIONS: On the
      basis of the results obtained, the authors affirm the validity and efficacy of
      tamoxifen in the treatment of mastodynia in PMS owing to both its innocuity and
      its atoxity.

PMID- 9595925
TI  - [Authors' experience with medical therapy of herpes genitalis in pregnancy].
AB  - BACKGROUND: Neonatal risk in herpes infections is very high: in the USA it is
      1:2,000, in Japan 1:15,000 and in England 1:65,000. These differences seem to be
      due mostly to the different risk factors associated to the mother infection. The
      best strategy to cure herpes infection is to examine every patient during
      pregnancy and to identify the high risk ones. METHODS: In this study, 1,860
      pregnant women have been submitted to a colposcopic and cytologic screening for
      the research of HSV. RESULTS: HSV was found in twenty (1.07%) women. Two groups
      have been made: the first with 14 HSV positive women at 3-6 months of pregnancy
      and second with 6 HSV positive women at eight months of pregnancy. Both groups
      were treated with acyclovir per os. The 14 women of the first group underwent
      vaginal delivery. The women of the second group underwent cesarean section. Only
      in 1 case a neonatal infection has been observed.

PMID- 9595926
TI  - [Therapy of bacterial vaginosis. Prospective clinical study ot the efficacy and
      tolerability of quaternary ammonium salts vs. clindamycin].
AB  - BACKGROUND: To evaluate the efficacy and safety of intravaginal quaternary
      ammonium antimicrobial compounds (SQA) versus clindamycin 2% intravaginal cream
      (CL) in the treatment of bacterial vaginosis (VB). MATERIALS AND METHODS: One
      hundred-thirty-three patients affected by VB were enrolled in the study from
      January 1995 to October 1997. Patients were classified according to Amsel's
      criteria and/or to the indications of the Scandinavian Society of Bacterial
      Vaginosis. Twenty-three patients were initially excluded from the study, and 110
      patients were randomized in two groups, SQA versus CL. Patients were reevaluated
      after 3 weeks, 3 months and 6 months from the end of therapy. The safety of
      treatment was also investigated. RESULTS: Of 110 patients, 59 were treated with
      SQA and 51 with CL. One hundred (90.9%) patients completed the therapy and were
      subjected to the first control after 3 weeks from the end of therapy. A
      significant reduction of most of the symptoms and all signs of VB was observed in
      the group treated with SQA. Similarly, a significant reduction of most of the
      symptoms (vaginal and urinary in particular) and all signs of VB was observed in
      the group treated with CL. The percentage of response was 86.7% for SQA group and
      87.2% for CL group. Moreover, after 3 months from the end of therapy, 47.2% and
      50% of the patients treated with SQA and CL, respectively, recurred, and after 6
      months 78.5% and 75% of the patients recurred, respectively. CONCLUSIONS: SQA
      treatment conferred 86.7% of response after 3 weeks from the end of therapy, with
      poor side effects and a good compliance in good keeping with the results obtained
      with CL treatment.

PMID- 9595927
TI  - [Non-invasive diagnosis of arteriosclerosis].
AB  - The author gives an overview about possibilities of noninvasive diagnostic ways
      in peripheral arterial occlusive disease. An exact diagnosis of macrocirculation
      pathology can be achieved by these methods and their combinations. The importance
      of non-invasive diagnostic methods concerning alteration of microcirculation--as
      indicators of chronic critical leg ischemia--is emphasized. According to the
      conclusion of the overview by noninvasive diagnostic evaluation of peripheral
      arterial occlusive disease an early diagnosis and an objective assessment become
      possible. The use of these diagnostic methods has advantage in eliminating of the
      risk factors, planning adequate therapy and as a final result improving the
      prognosis.

PMID- 9595928
TI  - [The role of jejunal feeding in the treatment of acute necrotizing pancreatitis
      and in recurrence of chronic pancreatitis with severe necrosis].
AB  - Acute necrotising is the most serious form of pancreatic inflammatory diseases
      leading to multiorgan failure and high (15-20%) mortality. The poor nutritional
      and metabolic condition of the patient and secondary bacterial translocation
      further rise the mortality. A recently introduced method of continuous
      nasojejunal feeding putting the pancreas into rest with basal pattern of
      secretion resulted in lower mortality rate by using adequate nutrition into the
      second loop of jejunum bypassing duodenopancreatic stimulations via an
      endoscopically placed feeding tube. The better nutritional and immunological
      states of the patients, the restored absorption and intestinal motility promote
      the recovery of pancreatitis, prevent bacterial translocation, resulting in time
      and in financial spares. Although surgery is occasionally inevitable because of
      progression of pancreatitis, nasojejunal feeding improves the general condition
      of patients more efficiently than parenteral nutrition and makes the scheduling
      of the operation optimal. The authors retrospectively analyse the results of
      treatment in 56 patients suffering from acute necrotising pancreatitis, as well
      as in 30 patients with chronic pancreatitis accompanied with more than 20% of
      necrosis in the pancreas and admitted to their gastroenterological medical
      department during 5 years. The effect of parenteral nutrition were less
      beneficial than that of jejunal feeding regarding the mortality and the necessity
      of operative interventions. Chronic pancreatitis with severe necrosis behaved
      similarly to the acute necrotising pancreatitis. The continuous nasojejunal
      feeding seems to be a promising new method for acute necrotising pancreatitis
      preventing complications and severe catabolic state of the disease by a cost-
      effective manner.

PMID- 9595930
TI  - [The DNA-chip, a new tool for medical genetics].
AB  - The DNA (chip) technology, emerged in the last two years, provides an incredible
      technical development in rapid and automatised performance of genetic
      identification. The principle of procedure is, that by series of photolitographic
      and chemical steps on solid-phase of a small surface relatively dense
      oligonucleotide arrays can be generated. The oligonucleotides produced by the
      computer-directed in-situ microfabrication may bind complementary fluorescent
      labeled DNA fragments from the unknown sample. After scanning, the registered
      position of positive signals provide information on the identity of DNA
      fragments. By this novel approach not only DNA sequencing can be performed, but
      genetic errors of known genes, presence of infectious organisms and the typing of
      genetic markers (such as HLA) used for transplantation and forensic medicine can
      be determined. The DNA-chip technology is a revolutionary new milestone in
      genetic diagnose.

PMID- 9595929
TI  - [Changes in urinary enzyme activity following silicon therapy of vesico-ureteral
      reflux].
AB  - The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP),
      Leucine-Arylamidase (LAS) and Dipeptidyl-Peptidase-IV (DPP-IV) were measured
      before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two
      groups of twenty children's. Ten patients had undergone successful endoscopic
      corrective surgery for VUR, another 10 patients had unsuccessful endoscopic
      intervention. After successful treatment the activity of LAS in the urine did not
      change, but that of GGT, ALP and DDP-IV activity in the urine was 2-5 times
      higher than before treatment (P < 0.03 for all three enzymes). Considerable
      changes of urinary enzymes' activity were not observed following unsuccessful
      endoscopic treatment. Our data and the literature are contradictory. However this
      contradiction might be explained by the differences in urine sampling methods.
      Our patients received the same chemoprofilactic drug at the time of both urine
      sampling, a point not considered by other researchers. The extent of increase of
      enzyme activity after endoscopic treatment of VUR did not reach the level that
      would permit the use of investigated enzymes for screening, because the observed
      changes did not exceed the limits of the normal range.

PMID- 9595931
TI  - [Severe lead poisoning caused by an ingested fishing weight].
AB  - Authors describe the case-history of a 17 year old male who accidentally ingested
      a fishing weight that was retained in the stomach and caused a serious lead
      poisoning. It is worth mentioning that beside the wellknown symptoms and signs of
      lead intoxication also the liver was seriously affected. The histologically
      verified toxic lesion of the liver presumably can be attributed to the large
      quantities of lead absorbed within a short period. This also explains the
      appearance of symptoms and signs indicating to encephalopathy beside the young
      age of the patient. The foreign body could not be removed by means of
      gastroscopy, therefore a gastrotomy was carried out followed by chelating
      treatment with i.v. CaNa2EDTA that resulted in complete clinical and laboratory
      recovery. The case history draws the attention to the importance of the quick
      removal of the retained lead containing objects out of the gastrointestinal
      tract.

PMID- 9595932
TI  - [Paleopathology of the hearing organ].

PMID- 9595933
TI  - [The disease of Miklos Revai].

PMID- 9595934
TI  - [Esophageal motor function and gastro-esophageal reflux esophagitis].

PMID- 9595936
TI  - Laparoscopic surgery without pneumoperitoneum.
AB  - The results of 43 laparoscopic surgeries performed with an abdominal wall
      retractor designed in the 3rd Surgical Service at "San Roque" Hospital are
      analyzed. Of them, 42 underwent cholecistectomy and one an endometrosic focus
      resection, placed in the Douglas sac. The results obtained have been good. There
      was almost no postoperatory pain due parietal wall traction. The hospital stay
      was less than 24 hours in 41 cases and less than 48 hours in two. We also point
      out the absence of complications and the advantages of the parietal traction
      compared with pneumoperitoneum.

PMID- 9595935
TI  - Manometry and 24-hour ambulatory pH monitoring at two levels of the esophagus in
      patients with and without esophagitis.
AB  - OBJECTIVE: To define the relationship between esophageal dysmotility and severity
      of gastroesophageal reflux (GER) at the distal and proximal levels. METHODS: Two
      level, 24-hour ambulatory pH monitoring and manometry of the esophagus were
      performed in 40 patients with abnormal distal acid exposure and in 20 healthy
      controls. Twenty patients with normal endoscopy or endoscopic evidence of grade I
      esophagitis were assigned to group 1 and 20 with grade II-III esophagitis were
      assigned to group 2. We used a dual-site pH probe with antimony electrodes spaced
      15 cm apart. RESULTS: Patients had greater acid exposure than controls at both
      levels. The percentage of distal reflux episodes reaching proximal esophagus was
      significantly greater in group 1 than in the control group. The most marked
      reductions in the percentage of time of the pH remaining under 4 were detected in
      the patients with the most severe distal acid reflux and esophagitis (group 2).
      The mean lower esophageal sphincter pressure was significantly lower in group 2
      than in group 1. The percentage of tertiary waves or nonperistaltic contractions
      was significantly higher in group 2 than in group 1 and the control group.
      Patients with milder distal reflux had significantly lower distal and middle
      esophageal wave amplitudes than controls. There were no significant differences
      between controls and patients with severe esophagitis in terms of the esophageal
      peristaltic wave amplitude in the middle third of the esophagus. CONCLUSIONS: No
      correlation was observed between episodes of distal reflux and proximal reflux in
      GER patients. Esophageal motor activity appears to be an important determinant of
      the severity and extension of GER in the proximal esophagus.

PMID- 9595937
TI  - Morphometric and proliferative effects of growth hormone on radiation enteritis
      in the rat.
AB  - Radiation enteritis is a common occurrence after radiotherapy in patients with
      abdominal tumors. Growth hormone may modify the response of the intestinal mucosa
      to radiation through its effects on the cell cycle or by increasing cell mass.
      The aim of this study is to determine the effects of growth hormone in the
      radiation-induced morphoproliferative changes in the intestinal mucosa. MATERIAL
      AND METHODS: An intestinal mucosal lesion was induced in adult male Wistar rats
      by means of abdominal irradiation with a lethal dose (LD50) of 1200 cGy. All
      animals received treatment with either saline or growth hormone for 7 days after
      irradiation. The animals were sacrificed on day 7. Body weight was determined the
      morphoproliferative status of the intestinal mucosa was assessed and the
      disaccharidase activity was measured. RESULTS: Growth hormone reduced body weight
      loss and increased mucosal length in irradiated rats. Mucosal proliferation was
      incremented in both irradiated and nonirradiated growth hormone-treated rats.
      Disaccharidase activity levels were similar to or higher than control values in
      all treated groups. CONCLUSION: Administration of growth hormone to irradiated
      rats reduces intestinal injury, probably as a consequence of an earlier recovery
      of intestinal morphology and functional status.

PMID- 9595938
TI  - Ambulatory liver biopsy: complications and evolution in 264 cases.
AB  - AIM: To determine the safety and acceptance of outpatient liver biopsies.
      PATIENTS AND METHODS: Data from all liver biopsies were collected in a
      prospective way over a period of 18 months. Information was gathered on
      complications, evolution of patients outside the hospital and opinion relating to
      the test. All patients were required to previously present: platelet count >
      60.000/mm3 prothrombin time within 4 seconds of control and absence of ascites or
      encephalopathy. Criteria for outpatient liver biopsy also included cooperative
      patient, a partner or friend who stayed with the patient during 12-24 hours
      following the test and easy access to the hospital. Out of a total of 378
      biopsies, 264 (70%) were ambulatory. RESULTS: Five of the 264 outpatients were
      hospitalized (1.9%), due to a subcapsular hematoma in one case, persistent pain
      in 3 cases and sever hypotension in the other; all of them evolved favorably in
      the first 24 hours. Among the inpatients, 2 had complications (1.7%): one
      subcapsular hematoma resolved without treatment and one abdominal hemorrhage
      requiring transfusion. Of the ambulatory patients, 46 (18%) presented pain whilst
      at home, being more frequent in females than in males (30% vs 15%, p = 0.004) and
      in those who needed more than one attempt to obtain histological material
      compared with those of a single attempt (33% vs 17%; p = 0.008). Twenty four
      hours after the test, 83% of the patients had returned to their normal
      activities. Ninety five percent of the patients questioned considered that the
      test was not traumatic, and 88% stated a preference for liver biopsy as a day
      case procedure. CONCLUSIONS: Liver biopsy performed on an ambulatory basis is
      safe, well tolerated and acceptable by the majority of patients.

PMID- 9595939
TI  - [Primary intestinal T lymphoma].
AB  - Primary gastrointestinal lymphoma comprises a group of distinctive
      clinicopathological entities. They may be of B or T-cell type. Intestinal T-cell
      lymphomas are much less common and include the entity: lymphomas T enteropathy
      associated T-cell lymphoma, the most common, and T-cell lymphoma without features
      of enteropathy. The morphologic and immunologic findings suggest that derived
      from mucosal T lymphocytes population. Clinically, the patients were usually
      males with constitutional symptoms and acute perforation and/or obstruction of
      the small bowel. Their prognosis are very poor and tumor are very aggressive.

PMID- 9595940
TI  - [Acute abdomen as a complication of a duodenal duplication cyst].
AB  - The authors report an exceptional case of acute abdomen caused by the necrosis
      and perforation of a duodenal duplication cyst in a 23 year-old-patient. The cyst
      was located at the anterior and lateral surface of the duodenum, between its
      first and second portion. The patient underwent a cephalic duodenopancreatectomy
      (Whipple's procedure) because of the intimate adherence of the necrotic and
      inflammatory mass to duodenum and head of the pancreas. The histological
      examination of surgical specimen confirmed the diagnosis, showing a cystic
      structure lined with an epithelium and a common muscle wall shared by the cyst
      and the duodenum. There was no communication between the cyst and duodenal lumen.

PMID- 9595941
TI  - [Diagnosis of biliary disease by endoscopic ultrasonography].

PMID- 9595942
TI  - [Focal fatty infiltration of the liver mimicking metastatic disease].

PMID- 9595943
TI  - [Mucocele of the appendix. Chest pain as clinical presentation].

PMID- 9595944
TI  - [Ultrasonography-hiatal hernia and gastro-esophageal reflux disease].

PMID- 9595945
TI  - [Ileal endometriosis as a cause of intestinal obstruction].

PMID- 9595946
TI  - Law requires physician supervision of CRNAs.

PMID- 9595947
TI  - Quality universal health care system needed.

PMID- 9595948
TI  - Resuscitation at the end of life: are slow codes acceptable?

PMID- 9595949
TI  - PPO black market.

PMID- 9595950
TI  - Technology to the rescue.

PMID- 9595951
TI  - Tracking a random killer.

PMID- 9595953
TI  - Town versus gown, the sequel.

PMID- 9595952
TI  - What's new in stroke?

PMID- 9595954
TI  - Friend of the court.

PMID- 9595955
TI  - Survey of the causes of stroke among Mexican Americans in South Texas.
AB  - Management strategies for optimal stroke prevention depend on the cause of
      threatened stroke. We know relatively little about the etiology of stroke in
      Mexican Americans, who make up one quarter of the population in Texas. A
      retrospective case series of 159 consecutive patients hospitalized in San
      Antonio, Tex, for acute, first-ever stroke compared risk factors, features, and
      causes of stroke between Mexican Americans and whites. Mexican Americans who had
      strokes were significantly younger than whites and had diabetes mellitus more
      often. Intracerebral hemorrhage and lacunar infarcts occurred often in Mexican
      Americans. Ethnicity appeared to be an independent risk factor for lacunar
      infarction. Mortality and functional outcome at the time of hospital discharge
      were similar in Mexican Americans and whites. Intrinsic small-vessel disease
      causing lacunar infarcts and intracerebral hemorrhage accounts for about one half
      of strokes in Mexican Americans. Stroke among Mexican Americans in South Texas
      has a distinctive profile with implications for its prevention.

PMID- 9595956
TI  - Elevated hepatitis A and E seroprevalence rates in a Texas/Mexico border
      community.
AB  - Two seroprevalence studies of viral hepatitis A and hepatitis E were conducted in
      El Paso, Tex, and Cd Juarez, Mexico. Subjects were randomly selected, low-income
      pregnant women. Blood from 557 women in El Paso and 307 women in Cd Juarez,
      obtained from routine prenatal testing, was analyzed for antibodies to hepatitis
      A and hepatitis E. Women from both cities showed high seroprevalence rates of
      hepatitis A (75.8% in El Paso and 96.1% in Cd Juarez). Rates increased
      significantly by age, with 100% of women in Cd Juarez older than 28 years testing
      positive. Nationality and ethnicity were significantly associated with hepatitis
      A seroprevalence: Mexican nationals, 96.1%; US Hispanics, 78.8%; and US
      Caucasians, 36.4% (P < .001). With respect to hepatitis E, 0.4% of women in El
      Paso and 1.6% of women in Cd Juarez tested positive for anti-HEV. The rate of
      hepatitis A seroprevalence was higher for women with lower educational levels and
      for women residing in crowded households, but these findings were not
      statistically significant.

PMID- 9595957
TI  - Pneumothorax in high school football.

PMID- 9595958
TI  - National Ambulatory Medical Care Survey: 1993 summary.
AB  - OBJECTIVE: This report describes ambulatory care visits made to private office
      based settings in the United States during 1993. Ambulatory medical care services
      are described in terms of physician, patient, and visit characteristics. METHODS:
      The data presented in this report are from the 1993 National Ambulatory Medical
      Care Survey (NAMCS). This survey is part of the ambulatory care component of the
      National Health Care Survey (NHCS), which measures health care utilization across
      a variety of providers. The NAMCS is a national probability sample survey of
      visits to office-based physicians in the United States. Sample data were weighted
      to produce annual estimates. RESULTS: During 1993, an estimated 717.2 million
      visits were made to physician offices in the United States, resulting in an
      average of 2.8 visits per person per year. This rate did not differ significantly
      from the overall visit rate of 3.0 in 1992. Females made 60 percent of the
      visits. White persons had a significantly higher rate of visits to physicians
      than black persons (3.0 visits per person per year and 1.8 visits per person per
      year, respectively). Over one-quarter (27.6 percent) of the visits were to
      general and family physicians. About 84 million, or 12 percent, of the visits
      were injury related. The annual rate of injury-related office visits was 33.0
      visits per 100 persons. Essential hypertension was the most common diagnosis made
      by physicians in 1993 as it has been since the survey began in 1973. Two-thirds
      of the visits resulted in another scheduled appointment and the mean duration was
      18 minutes.

PMID- 9595959
TI  - A human cerebral deconnection syndrome: a preliminary report. 1962.

PMID- 9595960
TI  - Frontal lobe neglect in man. 1972.

PMID- 9595961
TI  - Metrifonate for Alzheimer's disease: is the next cholinesterase inhibitor better?

PMID- 9595962
TI  - Antibodies to beta-interferons in multiple sclerosis: can we neutralize the
      controversy?

PMID- 9595963
TI  - Brain tumor therapy: new horizons, new hope.

PMID- 9595964
TI  - New lessons from old drugs: amantadine and Parkinson's disease.

PMID- 9595965
TI  - Limitations of quantitative sensory testing when patients are biased toward a bad
      outcome.

PMID- 9595967
TI  - Metrifonate benefits cognitive, behavioral, and global function in patients with
      Alzheimer's disease.
AB  - OBJECTIVE: To evaluate the efficacy and safety of metrifonate, an
      acetylcholinesterase inhibitor, in patients clinically diagnosed with probable
      Alzheimer's disease (AD) of mild to moderate severity. METHODS: A prospective, 36
      week, multicenter, double-blind, randomized, parallel group study of metrifonate
      in probable AD patients, including a 2-week screening period, a 26-week double
      blind treatment period, and a follow-up visit at 8 weeks post-treatment. A total
      of 24 ambulatory clinics in the United States in a variety of settings, including
      contract research organizations, public health facilities, and universities.
      Patients met diagnostic criteria for probable AD as defined by the work group of
      the National Institute for Neurological and Communicative Diseases and Stroke and
      the Alzheimer's Disease and Related Disorders Association. Patients had Mini
      Mental State Examination (MMSE) scores of 10 to 26 and Ischemic Scores (Rosen
      Modification) of <4. A total of 408 patients were enrolled. Percentages of
      patients completing double-blind treatment were 88% and 79% in the placebo and
      metrifonate groups, respectively. Rates of discontinuation due to adverse events
      were 4% in the placebo group and 12% in the metrifonate group. Placebo or
      metrifonate was administered once daily. Metrifonate-treated patients received a
      loading dose of 100 to 180 mg based on weight (2.0 mg/kg) for 2 weeks, followed
      by a maintenance dose of 30 to 60 mg based on weight (0.65 mg/kg) for 24 weeks.
      Primary efficacy variables were the Alzheimer's Disease Assessment Scale
      Cognitive Subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of
      Change with Caregiver Input (CIBIC-plus). Secondary efficacy variables included
      the Neuropsychiatric Inventory (NPI), the Disability Assessment in Dementia, the
      Global Deterioration Scale (GDS), the ADAS-Noncognitive subscale (ADAS-Noncog),
      the MMSE, and the Clinician's Interview-Based Impression of Severity with
      Caregiver Input (CIBIS-plus). Outcome measures reflected changes from baseline at
      week 26 for all variables. Safety was assessed with incidences of premature
      termination, treatment-emergent events and mortality, and routine safety
      evaluations. RESULTS: After 26 weeks of metrifonate therapy, a 2.86-point
      treatment difference (p = 0.0001) was observed in the ADAS-Cog scores of the
      intent-to-treat AD patients. The treatment difference in the mean CIBIC-plus
      score at this time was 0.28 points (p = 0.0071). At week 26, treatment
      differences also were observed in the mean NPI total score (p = 0.0161). Analysis
      of the remaining secondary efficacy variables showed treatment differences that
      favored metrifonate but did not reach statistical significance. Metrifonate
      adverse events were predominantly mild in intensity. No hepatotoxicity was
      observed. CONCLUSIONS: Metrifonate was safe and well-tolerated. It enhanced not
      only the cognitive and global function, but also the behavioral function of
      patients diagnosed with mild to moderate AD. Therefore, metrifonate appears to be
      useful in the symptomatic treatment of AD.

PMID- 9595966
TI  - Metrifonate treatment of the cognitive deficits of Alzheimer's disease.
      Metrifonate Study Group.
AB  - The efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, was
      evaluated clinically in patients diagnosed with mild to moderate Alzheimer's
      disease (AD). This was a prospective, 30-week, multicenter, double-blind,
      randomized, parallel group, dose-finding study, which included a 2-week screening
      period, a 12-week treatment period, and follow-up visits at 8 and 16 weeks post
      treatment. Patients received placebo or metrifonate once daily. Metrifonate
      treated patients received a loading dose of 0.5 mg/kg (25 to 45 mg), 0.9 mg/kg
      (45 to 80 mg), or 2.0 mg/kg (100 to 180 mg) for 2 weeks, followed by a
      maintenance dose of 0.2 mg/kg (10 to 20 mg), 0.3 mg/kg (15 to 25 mg), or 0.65
      mg/kg (30 to 60 mg) for 10 weeks. Four hundred eighty patients were enrolled.
      Percentages of patients completing double-blind treatment were 96% in the placebo
      group and 89 to 94% in the metrifonate group. Metrifonate significantly improved
      cognitive ability, as assessed by the Alzheimer's Disease Assessment Scale
      Cognitive Subscale (ADAS-Cog), and enhanced global function, as assessed the
      Clinicians's Interview-Based Impression of Change with Caregiver Input (CIBIC
      Plus). At 3 months, in the intent-to-treat patients, the treatment difference for
      the change in ADAS-Cog score in favor of metrifonate was 2.94 points (95% CI,
      1.61 to 4.27; p = 0.0001). These patients also exhibited a 0.35-point improvement
      on the CIBIC-Plus relative to the placebo patients (95% CI, 0.15 to 0.54; p =
      0.0007). Patients receiving lower drug doses had scores intermediate to those of
      the placebo and the 0.65 mg/kg metrifonate groups on both performance scales. The
      drug was well tolerated; side effects were predominantly gastrointestinal in
      nature, and no hepatic toxicity was observed. Therefore, in this study,
      metrifonate safely improved the cognitive deficits and benefited the global
      function of AD patients.

PMID- 9595968
TI  - The effect of education on dementia occurrence in an Italian population with
      middle to high socioeconomic status.
AB  - OBJECTIVE: To explore the relation between education and dementia prevalence by
      computing the odds ratios (ORs) for different educational levels after adjustment
      for age, gender, occupational level, and life habits. METHODS: A two-phase
      community study including 495 elderly subjects with middle to high socioeconomic
      status, aged more than 60 years and with a high percentage of noneducated
      subjects, was carried out in the province of Ravenna, Italy. Dementia and
      dementia type were clinically diagnosed using DSM-III-R diagnostic criteria.
      RESULTS: A higher prevalence of dementia was observed among noneducated subjects
      of both genders. Comparing no education with any education, the OR (adjusted for
      age, gender, and occupation) was 4.7 (95% CI = 2.3 to 9.6). The association,
      although present in all age groups, was extraordinarily strong among the youngest
      subjects (61 to 69 years) (OR = 139.5, 95% CI = 6.4 to 3,024.6) and decreased
      with increasing age. Life habits, such as smoking and alcohol consumption as well
      as current or previous history of hypertension, did not change the results. There
      was no significant difference in dementia prevalence among less well-educated (up
      to 3 years of education) and better-educated subjects (more than 3 years of
      schooling) after age and gender were taken into account. Similar findings were
      found for Alzheimer's disease and vascular dementia separately. CONCLUSIONS:
      Having no education is associated with dementia independent of gender,
      occupation, life habits, and hypertension. This association was stronger among
      younger old persons, and decreased with increasing age. The findings suggest that
      the first decade of life is a critical period for developing dementia later in
      life. The decrease in dementia risk may be due to schooling, according to the
      cerebral reserve hypothesis, or to other factors associated with a higher
      educational level during childhood.

PMID- 9595969
TI  - Cognitive test performance among nondemented elderly African Americans and
      whites.
AB  - We examined the neuropsychological test performance of a randomly selected
      community sample of English-speaking non-Hispanic African American and white
      elders in northern Manhattan. All participants were diagnosed as nondemented by a
      neurologist, whose assessment was made independent of neuropsychological test
      scores. African American elders obtained significantly lower scores on measures
      of verbal and nonverbal learning and memory, abstract reasoning, language, and
      visuospatial skill than whites. After using a stratified random sampling
      technique to match groups on years of education, many of the discrepancies became
      nonsignificant; however, significant ethnic group differences on measures of
      figure memory, verbal abstraction, category fluency, and visuospatial skill
      remained. Discrepancies in test performance of education-matched African
      Americans and whites could not be accounted for by occupational attainment or
      history of medical conditions such as hypertension and diabetes. These findings
      emphasize the importance of using culturally appropriate norms when evaluating
      ethnically diverse elderly for dementia.

PMID- 9595970
TI  - Brain size, head size, and intelligence quotient in monozygotic twins.
AB  - Many studies of monozygotic (MZ) twins have revealed evidence of genetic
      influences on intellectual functions and their derangement in certain neurologic
      and psychiatric diseases afflicting the forebrain. Relatively little is known
      about genetic influences on the size and shape of the human forebrain and its
      gross morphologic subdivisions. Using MRI and quantitative image analysis
      techniques, we examined neuroanatomic similarities in MZ twins and their
      relationship to head size and intelligence quotient (IQ). ANOVA were carried out
      using each measure as the dependent variable and genotype, birth order, and sex,
      separately, as between-subject factors. Pairwise correlations between measures
      were also computed. We found significant effects of genotype but not birth order
      for the following neuroanatomic measures: forebrain volume (raw, p < or = 0.0001;
      normalized by body weight, p = 0.0003); cortical surface area (raw, p = 0.002;
      normalized, p = 0.001); and callosal area (raw, p < or = 0.0001; normalized by
      forebrain volume, p = 0.02). We also found significant effects of genotype but
      not birth order for head circumference (raw, p = 0.0002; normalized, p < or =
      0.0001) and full-scale IQ (p = 0.001). There were no significant sex effects
      except for raw head circumference (p = 0.03). Significant correlations were
      observed among forebrain volume, cortical surface area, and callosal area and
      between each brain measure and head circumference. There was no significant
      correlation between IQ and any brain measure or head circumference. These results
      indicate that: 1) forebrain volume, cortical surface area, and callosal area are
      similar in MZ twins; and 2) these brain measures are tightly correlated with one
      another and with head circumference but not with IQ in young, healthy adults.

PMID- 9595971
TI  - Human anterior intraparietal area subserves prehension: a combined lesion and
      functional MRI activation study.
AB  - It has been shown in nonhuman primates that the posterior parietal cortex is
      involved in coordination of arm and eye movements in space, whereas the anterior
      intraparietal area in the anterior lateral bank of the intraparietal sulcus plays
      a crucial role in fine finger movements, such as grasping. In this study we show
      by optoelectronic movement recordings that patients with cortical lesions
      involving the anterior lateral bank of the intraparietal sulcus have selective
      deficits in the coordination of finger movements required for object grasping,
      whereas reaching is much less disturbed. Patients with parietal lesions sparing
      the cortex lining the anterior intraparietal sulcus showed intact grasping
      behavior. Complementary evidence was obtained from functional MRI in normal
      control subjects showing a specific activation of the anterior lateral bank of
      the intraparietal sulcus during grasping. In conclusion, this combined lesion and
      activation study suggests that the anterior lateral bank of the intraparietal
      sulcus, possibly including the human homologue of the anterior intraparietal
      area, mediates the processing of sensorimotor integration of precisely tuned
      finger movements in humans.

PMID- 9595972
TI  - Dissociation between verbal and autonomic measures of memory following frontal
      lobe damage.
AB  - OBJECTIVE: The objective of this study was to contrast overt verbal versus covert
      autonomic responses to facial stimuli in a patient with false recognition
      following frontal lobe damage. BACKGROUND: False recognition has been linked to
      frontal lobe dysfunction. However, previous studies have relied exclusively on
      overt measures of memory and have not examined whether or not patients with false
      recognition continue to demonstrate preserved covert discrimination of familiar
      and unfamiliar items. METHODS: We recorded skin conductance responses (SCRs) in a
      patient with frontal lobe damage and in normal control subjects while they
      performed a familiarity decision task using famous and unfamiliar faces as
      stimuli. RESULTS: Patient J.S. produced significantly more overt false
      recognition errors and misidentifications in response to unfamiliar faces than
      control subjects. However, similar to the control subjects, he showed accurate
      covert autonomic discrimination of truly familiar faces from unfamiliar ones.
      Furthermore, SCRs to falsely recognized unfamiliar faces were not significantly
      different from SCRs generated to unfamiliar faces that J.S. correctly rejected.
      CONCLUSIONS: Our findings provide further neuropsychological evidence that overt
      and covert forms of face recognition memory are dissociable. In addition, the
      failure to detect an autonomic correlate for the false recognition errors and
      misidentifications in J.S. suggests that these memory distortions were not
      related to the spurious activation of stored memory representations for specific
      familiar faces. Instead, these incorrect responses may have been driven by the
      sense of familiarity evoked by novel faces that had a general resemblance to
      faces encountered previously. We propose that false recognition in J.S. resulted
      from the breakdown of strategic frontal memory retrieval, monitoring, and
      decision functions critical for attributing the experience of familiarity to its
      appropriate source.

PMID- 9595973
TI  - Incidence and significance of neutralizing antibodies to interferon beta-1a in
      multiple sclerosis. Multiple Sclerosis Collaborative Research Group (MSCRG)
AB  - BACKGROUND: Interferon beta is an effective treatment for relapsing multiple
      sclerosis (MS). As with other protein drugs, neutralizing antibodies (NAB) can
      develop that reduce the effectiveness of treatment. OBJECTIVES: To determine the
      incidence and biological significance of NAB to interferon beta-la (IFN-beta-1a;
      Avonex; Biogen, Cambridge, MA) in MS patients. METHODS: A two-step assay for NAB
      to IFN-beta-1a was developed and used to assay serum samples from participants in
      the phase III clinical trial of IFN-beta-1a, and from patients in an ongoing open
      label study of IFN-beta-1a. The biological significance of NAB to IFN-beta-1a was
      determined by relating the NAB assay result to in vivo induction of the IFN
      inducible molecules neopterin and beta-2 microglobulin, and the clinical
      significance was determined by comparing clinical and MRI measures of disease
      activity after 2 years of IFN-beta-1a therapy in patients who were NAB+ and NAB-.
      The incidence of NAB was compared in MS patients who had used only IFN-beta-1a
      with the incidence in MS patients who had used only IFN-beta-1b. RESULTS: In
      patients in the open-label study, development of NAB to IFN-beta-1a resulted in a
      titer-dependent reduction in neopterin induction after interferon injections. In
      patients in the phase III study, development of NAB was associated with a
      reduction in beta-2 microglobulin induction. In the phase III study, a trend
      toward reduced benefit of IFN-beta-1a on MRI activity in NAB+ versus NAB-
      patients was observed. The incidence of NAB to IFN-beta-1a in the open-label
      study was approximately 5% over 24 months of treatment of IFN-beta-1a therapy,
      but was four- to sixfold higher using the same assay for patients exposed only to
      IFN-beta-1b for a similar duration. There were no clinical, MRI, or CSF
      characteristics that were predictive of which patients would develop NAB.
      CONCLUSIONS: NAB directed against IFN-beta have in vivo biological consequences
      in patients with MS. The frequency with which MS patients develop NAB against IFN
      beta is significantly greater with IFN-beta-1b therapy compared with IFN-beta-1a
      therapy. Treatment decisions in MS patients treated with IFN-beta should take
      into account development of NAB.

PMID- 9595974
TI  - Intravenous immunoglobulin G reduces MRI activity in relapsing multiple
      sclerosis.
AB  - We wanted to assess whether intravenous immunoglobulin G (IVIG) decreases disease
      activity on MRI in relapsing MS. Previous trials of IVIG in relapsing-remitting
      MS demonstrated a reduction of acute relapses, but these studies did not include
      MRI. We treated 26 patients in a randomized, double-blind, crossover study of
      IVIG 1 g/kg daily or placebo on 2 consecutive days every month during two 6-month
      treatment periods. The primary end point was the number of gadolinium-enhancing
      lesions on monthly serial MRI. Secondary efficacy variables were the occurrence
      of exacerbations, clinical neurologic ratings, total MS lesion load on T2
      weighted MRI, and multimodal evoked potentials. Eighteen patients completed the
      entire trial; eight patients did not. Twenty-one patients completed the first
      treatment period and at least two MRI examinations in the second treatment period
      and were included in the intention-to-treat analysis. On serial MRI, we observed
      fewer enhancing lesions per patient per scan during IVIG treatment (median, 0.4;
      range, 0 to 9.3) than during placebo treatment (median, 1.3; range, 0.2 to 25.7;
      p = 0.03). During IVIG treatment, 15 patients were exacerbation free compared
      with only 7 on placebo (p = 0.02). The total number of exacerbations in the IVIG
      period was 11 and in the placebo period, 19 (not significant). None of the
      remaining secondary efficacy measures were significantly different between the
      two treatment periods. The number of adverse events, in particular eczema, was
      significantly higher during IVIG therapy than during placebo treatment. These
      results suggest that IVIG treatment is beneficial to patients with relapsing MS.

PMID- 9595975
TI  - Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in
      multiple sclerosis.
AB  - Postmortem unfixed whole brains from five multiple sclerosis (MS) patients were
      examined by MRI using a T2- and T1-weighted spin-echo (SE) sequence and histology
      to investigate the histopathologic characteristics of hypointense lesions on T1
      weighted SE MR images. The degree of hypointensity was scored semiquantitatively
      by two blinded observers in reference to normal-appearing white matter. Signal
      intensities of the lesions and the normal-appearing white matter were measured to
      obtain contrast ratios. Hematoxylin-eosin stain was used to assess degree of
      matrix destruction (decrease of density of the neuropil) and cellularity of a
      lesion, Kluver-Barrera stain for degree of demyelination, Bodian stain for axonal
      density, and immunostaining of glial fibrillary acid protein for reactive
      astrocytes and fibrillary gliosis. Nineteen lesions were selected for analysis.
      Nearly all lesions were compatible with the chronic MS plaque: hypocellularity,
      absence of myelinated axons, in the presence of reactive astrocytes. Contrast
      ratios of the lesions were highly correlated (R = -0.90; p < 0.01), with degree
      of hypointensity scored semiquantitatively. Degree of hypointensity on T1
      weighted SE images did not correlate with degree of demyelination or number of
      reactive astrocytes, but was associated with axonal density (R = -0.71; p =
      0.001). A trend was found with degree of matrix destruction (R = 0.45; p =
      0.052). We conclude that, in our limited sample, hypointense lesions seen on T1
      weighted SE MR images are associated histopathologically with severe tissue
      destruction, including axonal loss. Our results need to be substantiated in a
      larger study on more varied patient material to evaluate the use of hypointense
      lesions as a surrogate marker of persistent deficit in MS patients.

PMID- 9595976
TI  - Magnetization transfer ratios in multiple sclerosis lesions enhancing after
      different doses of gadolinium.
AB  - We performed serial monthly magnetization transfer (MT) imaging to evaluate
      whether MS lesions that enhance only after the injection of a triple dose (TD) of
      gadolinium-DTPA (Gd) have different pathologic characteristics and evolution than
      those that enhance after the injection of a standard dose (SD). Every 4 weeks for
      3 months and in two separate sessions, we obtained T1-weighted scans from 10
      patients with relapsing-remitting MS, 5 minutes after SD (0.1 mmol/kg) or TD (0.3
      mmol/kg) Gd injection. During each of the first monthly sessions, we obtained MT
      images and dual-echo scans before Gd injection. We measured the MT ratio (MTR) of
      newly enhancing lesions on co-registered quantitative MTR images. During the 3
      month follow-up, 81 newly enhancing lesions were seen on SD scans. An additional
      46 lesions enhanced only on TD scans. The mean (+/- standard deviation) MTR
      values were 31.4% +/- 8.4% for lesions enhancing after SD and 38.2% +/- 6.0% for
      lesions enhancing only after TD injection (p < 0.0001). The mean MTR values of
      lesions seen with both SD (p < 0.00001) and TD (p = 0.002) increased
      significantly during the follow-up. At each time point during the follow-up, the
      MTR values of TD lesions were significantly higher than the SD lesions. These
      results indicate that the enhancing lesion population in MS is heterogeneous and
      that the tissue damage occurring within lesions enhancing only after TD injection
      is less severe than in lesions enhancing after the injection of an SD.

PMID- 9595977
TI  - In vivo effects of interferon beta-1a on immunosuppressive cytokines in multiple
      sclerosis.
AB  - Recombinant interferon beta (IFNbeta) benefits patients with relapsing remitting
      multiple sclerosis (MS), but the mechanisms of action are unknown. We studied in
      vivo immunologic effects of IFNbeta treatment and their relationship to clinical
      efficacy. Cytokines were measured in blood and CSF from MS patients participating
      in a placebo-controlled phase III clinical trial and an open-label phase IV
      [corrected] tolerability study of IFNbeta-1a. Additionally, immunologic studies
      were conducted in animals with proteolipid protein (PLP)-induced chronic
      relapsing experimental autoimmune encephalomyelitis. Single intramuscular (IM)
      injections of IFNbeta-1a (6 MIU, 30 microg) were associated with significant in
      vivo upregulation of interleukin-10 (IL-10) and IL-4 but not IFNgamma mRNA in
      peripheral blood mononuclear cells. Forty-eight hours after each IFNbeta-1a
      injection, serum IL-10 levels increased and remained elevated for 1 week. IFNbeta
      1a recipients in the placebo-controlled phase III clinical trial showed
      significantly increased concentrations of CSF IL-10 after 2 years of treatment.
      This response correlated with a favorable therapeutic response. Exposure of PLP
      reactive murine T-cell lines to IFNbeta resulted in increased antigen-driven
      expression of IL-4 and IL-10 and reduced encephalitogenicity. IFNbeta-1a
      injections induce systemic and intrathecal immunosuppressive cytokines. Myelin
      specific T cells treated with IFNbeta-1a demonstrate increased immunosuppressive
      cytokine expression and reduced encephalitogenicity. The relationship between
      increased CSF IL-10 and response to therapy suggests that induction of IL-10 is a
      mechanism underlying IFNbeta-1a effects in MS patients.

PMID- 9595978
TI  - Isolated U-fiber involvement in MS: preliminary observations.
AB  - We studied the frequency and location of isolated U-fiber involvement in MS and
      correlated these findings exploratively with physical disability and
      neuropsychological impairment. Fifty-three MS patients were examined. Three
      millimeter-thick, fast spin-echo T2-weighted MR images and spin-echo
      postgadolinium T1-weighted images were obtained. Computer software that which had
      been validated previously for quantitation of MS lesions was used to detect
      lesions on the T2-weighted images. The Expanded Disability Status Scale (EDSS),
      Ambulation Index (AI), and a battery of neurocognitive tests were performed on
      each patient. Forty-two arcuate hyperintensities along the U-fiber were detected
      by the software in 28 patients (53%). Twenty-seven lesions (64.3%) were seen in
      the frontal lobe, eight (19.0%) in the temporal lobe, three (7.1%) in the
      parietal lobe, three (7.1%) in the occipital lobe, and one (2.4%) in both frontal
      and parietal lobes. Four lesions (9.5%) showed gadolinium enhancement. Seventeen
      lesions (40%) were hypointense on the T1-weighted images. Scores of three of the
      11 neuropsychological tests reflecting performance in executive control and
      memory were significantly different at least at the p = 0.05 level between the
      eight patients with multiple, isolated U-fiber lesions and the 45 patients
      without any or with only a single U-fiber lesion. No significant difference was
      noted for EDSS or AI. Isolated U-fiber involvement is an underappreciated MR
      finding in MS. Our preliminary hypothesis is that U-fiber lesions may contribute
      to neuropsychological impairment, although our observation requires confirmation.

PMID- 9595979
TI  - Suppression of human glioma growth by adenovirus-mediated Rb gene transfer.
AB  - OBJECTIVE: This study was conducted to obtain evidence that restoration of the
      retinoblastoma protein function may have therapeutic application for gliomas.
      BACKGROUND: The development of glioblastoma multiforme involves progressive
      inactivation of several tumor suppressor genes. Abnormalities of the
      retinoblastoma tumor suppressor gene are found in the majority of cancers,
      including at least 30% of malignant gliomas. No final evidence has been produced
      about the role of Rb in suppressing glioma growth. METHODS: To address this
      question, the Ad5CMV-Rb adenovirus carrying a 3.2-kb cDNA of the Rb gene was
      constructed. Expression of the exogenous protein was assessed by immunoblot and
      immunohistochemistry analyses. Growth curve assays were used to evaluate the
      effect of the Rb protein on glioma cell growth. Flow-cytometry analyses were used
      to analyze the phenotype of the cell cycle after the transfer of Rb. Human glioma
      xenografts implanted subcutaneously in nude mice were used for the tumorigenicity
      assay. RESULTS: After the transfer of Rb, 80% of the treated cells expressed high
      levels of the retinoblastoma protein for at least 7 days. Within 5 days of
      treatment, the cells lost the neoplastic morphology and showed marked growth
      suppression. The majority of the Rb-expressing cells were arrested in the G1
      phase of the cell cycle. In addition, the restoration of the retinoblastoma
      activity rendered the human glioma cells unable to form tumors in nude mice.
      CONCLUSIONS: These findings provide direct evidence that inactivation of the
      retinoblastoma protein is a critical event in gliomas, and suggest that the
      restoration of wild-type retinoblastoma activity in these tumors may have
      therapeutic utility.

PMID- 9595980
TI  - 11C-methionine PET for differential diagnosis of low-grade gliomas.
AB  - Management of low-grade gliomas continues to be a challenging task, because CT
      and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor
      extent and aggressiveness often remain unclear because of a lack of contrast
      enhancement. Previous studies indicated that large neutral amino acid tracers
      accumulate in most brain tumors, including low-grade gliomas, probably because of
      changes of endothelial and blood-brain barrier function. We describe 11C
      methionine uptake measured with PET in a series of 196 consecutive patients, most
      of whom were studied because of suspected low-grade gliomas. Uptake in the most
      active lesion area, relative to contralateral side, was significantly different
      among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral
      lesions, and this difference was independent from contrast enhancement in CT or
      MRI. Corticosteroids had no significant effect on methionine uptake in low-grade
      gliomas but reduced uptake moderately in high-grade gliomas. Differentiation
      between gliomas and nontumoral lesions by a simple threshold was correct in 79%.
      Recurrent or residual tumors had a higher uptake than primary gliomas. In
      conclusion, the high sensitivity of 11C-methionine uptake for functional
      endothelial or blood-brain barrier changes suggests that this tracer is
      particularly useful for evaluation and follow-up of low-grade gliomas.

PMID- 9595981
TI  - Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's
      disease.
AB  - OBJECTIVE: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist
      amantadine on levodopa-associated dyskinesias and motor fluctuations in
      Parkinson's disease (PD). BACKGROUND: NMDA receptor blockade can ameliorate
      levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well
      tolerated and modestly effective antiparkinsonian agent, was recently found to
      possess NMDA antagonistic properties. METHODS: Eighteen patients with advanced PD
      participated in a double-blind, placebo-controlled, cross-over study. At the end
      of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained
      during a steady-state intravenous levodopa infusion. Motor fluctuations and
      dyskinesias were also documented with patient-kept diaries and Unified
      Parkinson's Disease Rating Scale (UPDRS) interviews. RESULTS: In the 14 patients
      completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001)
      compared to placebo, without altering the antiparkinsonian effect of levodopa.
      Motor fluctuations occurring with patients' regular oral levodopa regimen also
      improved according to UPDRS and patient-kept diaries. CONCLUSIONS: These findings
      suggest that amantadine given as adjuvant to levodopa can markedly improve motor
      response complications and support the view that hyperfunction of NMDA receptors
      contributes to the pathogenesis of levodopa-associated motor complications.

PMID- 9595982
TI  - Levodopa improves motor function without impairing cognition in mild non-demented
      Parkinson's disease patients. Parkinson Study Group.
AB  - OBJECTIVE: The objective of the study was to determine the effects of short-term
      levodopa administration on motor, cognitive, and psychiatric aspects of
      Parkinson's disease (PD). BACKGROUND: The effects of levodopa on mental processes
      in PD are controversial. Opinions range from the claim that levodopa improves
      cognition to the opposite view that levodopa causes or exacerbates dementia,
      delusions, and hallucinations. Of the 800 idiopathic PD patients enrolled in the
      original DATATOP study, 387 reached the end point of functional disabilities
      sufficiently severe to require levodopa treatment. There were 263 men and 124
      women who were comparable with regard to age, symptom duration of PD, and
      measures of PD severity. We compared test scores on motor performance, cognitive
      function, and psychiatric status before levodopa and again within 6 months after
      initiation of levodopa therapy. RESULTS: Levodopa administration improved all
      motor functions significantly. The improvement was significantly greater in women
      than in men. Levodopa administration did not worsen scores on any cognitive
      tests, and there were quantitatively small but significant improvements in tests
      of frontal lobe function. Levodopa exerted only minor effects on psychiatric
      measures. There were small but significant decreases in scores for depression,
      and increases in vivid dreams and hallucinations. CONCLUSIONS: Levodopa
      administration for up to 6 months in dosages sufficient to improve motor function
      has only small effects on cognitive function and psychiatric status in mild to
      moderate PD patients. We conclude that motor symptoms in early PD, which result
      from dopamine depletion, are dissociable from cognitive functions and psychiatric
      status, which may be more dependent on nondopaminergic mechanisms.

PMID- 9595983
TI  - A clinical, pharmacologic, and polysomnographic study of sleep benefit in
      Parkinson's disease.
AB  - We assessed the effect of sleep benefit on motor performance in Parkinson's
      disease (PD) and analyzed its relation to pharmacologic and sleep measures. The
      sleep benefit phenomenon-motor improvement after sleep before drug intake-in
      patients with PD has been addressed by questionnaire studies, but objective data
      are scarce. Ten PD patients with sleep benefit were pairwisely matched to 10 PD
      patients without sleep benefit for gender, age, PD symptom duration, and
      medications. We examined motor performance at night before sleep, during morning
      baseline state immediately after spontaneous awakening, and continuously after
      intake of the usual levodopa dose. Plasma levodopa concentrations were measured
      serially and all-night polysomnography was performed. Between night and morning
      evaluations, motor state improved slightly in patients with sleep benefit and
      deteriorated slightly in patients without sleep benefit. The difference between
      both groups proved to be significant. After levodopa induced "on" state, patients
      with sleep benefit had more severe interdose "off" than those without. Levodopa
      concentrations and polysomnographic findings were similar in both conditions,
      although there was a trend toward more abnormal sleep measures in sleep benefit
      patients. Sleep benefit is a small but significant phenomenon. It does not
      clearly relate to a specific sleep variable; however, patients with sleep benefit
      showed a different response profile to levodopa. Subjective perception or
      possibly sensory mechanisms could play an additional role in sleep benefit in PD.

PMID- 9595984
TI  - Early onset parkinsonism with diurnal fluctuation maps to a locus for juvenile
      parkinsonism.
AB  - Early onset parkinsonism with diurnal fluctuation (EPDF) is a dopa-responsive
      parkinsonism characterized by early onset and improvement of parkinsonian
      symptoms after sleep. A pathologic study of one case of EPDF showed selective
      neuronal degeneration in the zona compacta of the substantia nigra without Lewy
      body formation. To determine the disease locus for EPDF, the authors examined 53
      members of 17 EPDF families and analyzed 151 meioses. Multipoint linkage analysis
      gave a peak lod score of 14.2 at 1.0 cM telomeric to D6S305 and placed the
      disease locus in the 17-cM interval between D6S437 and D6S253, which is exactly
      the same position mapped for autosomal recessive juvenile parkinsonism (ARJP;
      Mendelian inheritance in man 600116). The highest two-point lod score was
      obtained at D6S305 (10.13 at theta = 0). Haplotype analysis agreed with the
      result of multipoint analysis. A high proportion of nonconsanguinity (8/17
      families), the absence of commonly shared haplotypes, and the widespread
      geographic distribution of the families' origins suggest that EPDF has multiple
      founder mutations. The authors concluded that EPDF and ARJP are allelic disorders
      and should be included in the spectrum of a single-clinicogenetic entity of
      chromosome 6q-linked parkinsonism. This disease could be characterized by a
      benign clinical course and relatively selective degeneration of nigral
      dopaminergic neurons with no Lewy body formation. To determine whether ARJP/EPDF
      constitutes a significant proportion of familial or sporadic forms of benign
      early onset parkinsonism will require further study.

PMID- 9595985
TI  - The risk of Parkinson's disease with exposure to pesticides, farming, well water,
      and rural living.
AB  - We assessed exposure to pesticides, farming, well water use, and rural living as
      risk factors for Parkinson's disease (PD) in a population-based case-control
      study consisting of men and women > or = 50 years of age who had primary medical
      care at Henry Ford Health System in metropolitan Detroit. Enrolled PD patients (n
      = 144) and control subjects (n = 464) were frequency-matched for age, race, and
      sex. When adjusted for these variables and smoking status, there was a
      significant association of occupational exposure to herbicides (odds ratio [OR],
      4.10; 95% CI, 1.37, 12.24) and insecticides (OR, 3.55; 95% CI, 1.75, 7.18) with
      PD, but no relation was found with fungicide exposure. Farming as an occupation
      was significantly associated with PD (OR, 2.79; 95% CI, 1.03, 7.55), but there
      was no increased risk of the disease with rural or farm residence or well water
      use. The association of occupational exposure to herbicides or insecticides with
      PD remained after adjustment for farming. The association of farming with PD was
      maintained after adjustment for occupational herbicide exposure and was of
      borderline significance after adjustment for occupational insecticide exposure.
      These results suggest that PD is associated with occupational exposure to
      herbicides and insecticides and to farming and that the risk of farming cannot be
      accounted for by pesticide exposure alone.

PMID- 9595986
TI  - Does a screening questionnaire for essential tremor agree with the physician's
      examination?
AB  - In research studies of essential tremor (ET), monetary and geographic factors
      often necessitate diagnosis by interview rather than by examination. Few attempts
      have been made to determine the validity of a screening instrument for ET. A
      total of 242 subjects (33 definite or probable ET, 54 possible ET, and 155
      normal) were part of a community-based family study of ET in northern Manhattan.
      Subjects underwent a tremor interview and videotaped tremor examination. The
      interview included 12 screening questions for ET. Two neurologists rated the
      severity of tremor on videotape and assigned diagnoses. The subjects' responses
      to the 12 screening questions were compared with the neurologic examination and
      the neurologists' diagnoses. There was an association between the number of
      affirmative responses on the 12-item screen and the severity of tremor during the
      videotaped tremor examination (r = 0.66, p < 0.01). Including those with probable
      and definite ET and defining a positive screen result as an affirmative response
      to at least 1 of 12 screening questions, the sensitivity of the screening
      questionnaire was 73%, the specificity was 96%, and the positive predictive value
      was 80%. The responses to the questionnaire closely correlated with the severity
      of tremor on neurologic examination. The questionnaire had moderate validity for
      subjects with probable or definite ET; subjects with mild ET often screened
      negative. Hence, in population-based studies and family studies of ET, it is
      important to examine all subjects for the presence of mild asymptomatic ET.

PMID- 9595987
TI  - 1H NMR spectroscopy studies of Huntington's disease: correlations with CAG repeat
      numbers.
AB  - Huntington's disease (HD) is the result of an expanded (CAG) repeat in a gene on
      chromosome 4. A consequence of the gene defect may be progressive impairment of
      energy metabolism. We previously showed increased occipital cortex lactate in HD
      using localized 1H spectroscopy. We have now extended these studies to show an
      almost threefold elevation in occipital cortex lactate in 31 HD patients as
      compared with 17 normal control subjects (p < 10(-11)). The spectra in three
      presymptomatic gene-positive patients were identical to normal control subjects
      in cortical regions, but three in eight showed elevated lactate in the striatum.
      Similar to recently reported increases in task-related activation of the striatum
      in the dominant hemisphere, we found that striatal lactate levels in HD patients
      were markedly asymmetric (higher on the left side). Markers of neuronal
      degeneration, decreased N-acetylaspartate (NAA)/creatine and increased
      choline/creatine levels, were symmetric. Both decreased NAA and increased lactate
      in the striatum significantly correlated with duration of symptoms. When divided
      by his or her age, an individual's striatal NAA loss and lactate increase were
      found to directly correlate with the subject's CAG repeat number, with
      correlation coefficients of 0.8 and 0.7, respectively. Similar correlations were
      noted between postmortem cell loss and age versus CAG repeat length. Together,
      these data provide further evidence for an interaction between neuronal
      activation and a defect in energy metabolism in HD that may extend to
      presymptomatic subjects.

PMID- 9595988
TI  - Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's
      disease. The Huntington Study Group.
AB  - Oxidative damage due to free-radical generation in the setting of underlying
      defects of neuronal energy metabolism has been implicated as a pathogenetic
      mechanism for Huntington's disease (HD). The authors conducted a randomized,
      double-blind, placebo-controlled, multicenter trial of the tolerability of OPC
      14117, a lipophilic free-radical scavenger that concentrates in the brain.
      Ambulatory patients with HD received OPC-14117 60 mg/d, 120 mg/d, 240 mg/d, or
      placebo and were assessed by the Unified Huntington's Disease Rating Scale
      (UHDRS) for 20 weeks, including 12 or 16 weeks of assigned treatment and 8 or 4
      weeks of blinded withdrawal of the study drug. Tolerability was measured by the
      proportion of patients completing the initial 12-week course of treatment on
      their originally assigned regimen. Sixty-four patients were enrolled in the
      study, 56 of whom completed the 12 weeks of treatment. Treatment was discontinued
      in four patients (1 placebo, 1 60 mg/d, 2 240 mg/d) due to asymptomatic but
      persistent serum elevations of liver transaminase. Two patients (1 60 mg/d and 1
      120 mg/d) withdrew because of increased involuntary movements, one patient (60
      mg/d) withdrew due to persistent dry eyes, and one patient (120 mg/d) withdrew
      because of persistent vomiting. There were no significant differences between
      treatment arms in the primary measures of tolerability, the frequency and types
      of clinical adverse events, or the clinical/functional features of HD. OPC-14117
      was safe and generally well tolerated; however, elevations of liver transaminase
      suggested that continued surveillance monitoring is warranted in conducting more
      long-term studies of this antioxidant therapy.

PMID- 9595989
TI  - Temporal lobe epilepsy in a genius of natural history: MRI volumetric study of
      postmortem brain.
AB  - Kumagusu Minakata (1867-1941), a Japanese genius devoted to natural history and
      folklore, is famous for his immense range of works, including his discovery of
      many new varieties of mycetozoa, or slime molds. His diary reveals that he was
      affected by epilepsy. In this study of his brain, we adopted a method of
      measuring the volume of the hippocampi by MRI of postmortem brain and found
      evidence of right hippocampal atrophy. This finding, together with the striking
      parallels between his behavior and the known behavioral syndrome in temporal lobe
      epilepsy (TLE), suggests that he was affected by TLE. The postmortem imaging
      analysis of brain, as performed in this study, offers a bridge between
      neuroscience and classic psychopathologic approaches to the creativity of
      geniuses.

PMID- 9595990
TI  - Recurrent seizures may cause hippocampal damage in temporal lobe epilepsy.
AB  - OBJECTIVE: To investigate whether recurrent seizures cause hippocampal damage in
      temporal lobe epilepsy (TLE). PATIENTS: Eighteen patients with newly diagnosed
      cryptogenic TLE, 14 patients with chronic well-controlled cryptogenic TLE, 32
      patients with chronic drug-resistant cryptogenic TLE, and 25 healthy subjects
      were studied. MEASUREMENTS: Hippocampal MRI volumetry and T2 relaxometry were
      used. RESULTS: Chronic drug-resistant patients with seizure focus in the left
      temporal lobe had an 18% smaller left hippocampus and chronic drug-resistant
      patients with seizure focus in the right temporal lobe had a 14% smaller right
      hippocampus than did the control group (p < 0.05). Chronic drug-resistant
      patients with seizure focus on the left side had longer T2 relaxation times in
      the body of the left hippocampus than did the control group (p < 0.001) and
      chronic drug-resistant patients with seizure focus on the right side had longer
      T2 relaxation times in the body of the right hippocampus than did the control
      subjects (p < 0.01). In all patients with a left seizure focus, the left
      hippocampal volume correlated inversely with the estimated total number of
      partial (r = -0.391, p < 0.01) or generalized (r = -0.312, p < 0.05) seizures the
      patient had experienced. The prolongation of the left T2 relaxation time in the
      body of the hippocampus correlated with the total number of both partial (r =
      0.670, p < 0.001) and generalized (r = 0.481, p < 0.001) seizures and with the
      duration of TLE symptoms (r = 0.580, p < 0.001). CONCLUSIONS: In patients with
      cryptogenic epilepsy, recurrent seizures may cause damage to the hippocampus
      throughout the lifetime of the patient.

PMID- 9595991
TI  - Sublobar dysplasia: a new malformation of cortical development.
AB  - We investigated the clinical presentations and neuroimaging characteristics of
      five patients with sublobar dysplasia, an unusual malformation of cortical
      development. Records and teaching files of five unrelated patients with a
      localized dysplasia of the cerebral hemisphere separated from the remainder of
      the affected lobe or hemisphere by a deep infolding of cortex (sublobar
      dysplasia) were retrospectively reviewed with regard to age at clinical
      presentation, manner of clinical presentation, neurologic examination, location
      of dysplasia, imaging characteristics, and the presence and type of associated
      malformations. Four of five patients presented with seizures; the fifth presented
      with a calvarial anomaly. All were neurologically and developmentally normal. MRI
      showed that the areas of sublobar dysplasia were frontal in two patients and
      temporal, parietal, and occipital in one patient each. The cortex in the affected
      region of brain was thickened with shallow sulci and an abnormal sulcal pattern
      in all affected patients. In three patients, the cortical-white matter junction
      was irregular. The ipsilateral lateral ventricle was dysplastic in all patients.
      Associated anomalies included callosal anomalies (five patients), cerebellar
      vermian hypoplasia (three patients), and venous malformation (one patient).
      Sublobar dysplasia appears to be a distinct cortical malformation of unknown
      etiology that causes no neurologic deficits but ultimately results in epilepsy.
      Possible causes include abnormal stem cell proliferation and in utero injury.

PMID- 9595992
TI  - Status epilepticus increases CSF levels of neuron-specific enolase and alters the
      blood-brain barrier.
AB  - Neuron-specific enolase (NSE) is a sensitive marker of brain damage in stroke,
      global ischemia, and coma. Serum NSE is also correlated with the duration and
      outcome of status epilepticus (SE). CSF-NSE levels have not been previously
      reported in SE. We report the CSF concentrations of NSE in 11 patients with
      cryptogenic/remote symptomatic SE. CSF obtained within 24 hours of SE showed
      increased concentrations of NSE in 9 of 11 patients. The mean CSF-NSE for the
      group was elevated compared with the levels for normal control subjects (30.8 +/-
      18.33 versus 10.76 +/- 3.08 ng/mL; p = 0.002). Further, CSF-NSE levels were
      elevated compared with simultaneous serum levels in the same group of patients (p
      = 0.01). In addition, the CSF/serum albumin ratio (QAlb), a measure of the
      integrity of the blood-brain barrier, was increased in SE patients compared with
      control individuals (33.4 versus 4.79 x 10(-3); p = 0.0001). An increase of QAlb
      correlated with CSF-NSE (rs = 0.66, p = 0.04) and serum NSE levels (rs = 0.83, p
      = 0.004). CSF-NSE is a promising in vivo marker for brain injury after SE.

PMID- 9595993
TI  - Absence of antibodies to non-NMDA glutamate-receptor subunits in paraneoplastic
      cerebellar degeneration.
AB  - OBJECTIVE: To determine whether patients with antineuronal antibody-associated
      paraneoplastic cerebellar degeneration (PCD) harbor antibodies to non-N-methyl-D
      aspartate glutamate receptors (GluRs) in their serum. BACKGROUND: A recent study
      identified antibodies to GluRs in the serum of patients with PCD. METHODS: Sera
      of 35 patients with PCD (20 anti-Yo, 5 anti-Ri, 5 anti-Tr, and 5 anti-Hu) were
      examined by immunohistochemistry and immunoblot techniques. The expression of
      GluRs was obtained after transfection of 293T cells with cDNA plasmids
      corresponding to GluR1, GluR2, GluR3, GluR4, GluR6, and GluR7. The tumors of four
      patients with anti-Yo-associated PCD and nine ovarian carcinomas from patients
      without PCD were examined for the expression of GluRs. RESULTS: The expression of
      each GluR subunit was confirmed using affinity-purified antibodies against the
      corresponding GluRs and with whole sera from two rabbits immunized with GluR3.
      Thirty-two sera from patients with PCD were negative and 3 showed equivocal
      reactivity with 293T cells expressing different GluRs. None of the 35 sera had a
      pattern of reactivity characteristic of any GluR antibody on immunohistochemistry
      of sections of rat brain. Eleven of 14 tumors did not express GluRs; only some
      cells of one paraneoplastic tumor expressed GluRs. CONCLUSIONS: That patients
      with antibody-associated PCD (anti-Yo, -Ri, -Tr, and -Hu) harbor GluR antibodies
      in their sera is unlikely. GluR antibodies cannot be used as markers of
      paraneoplastic neurologic disorders.

PMID- 9595994
TI  - Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein
      zero gene.
AB  - Charcot-Marie-Tooth disease (CMT), or hereditary motor and sensory neuropathy
      (HMSN), is a clinically and genetically heterogeneous condition. Mutations of the
      myelin protein zero (MPZ) gene have been associated with CMT1B, Dejerine-Sottas
      disease, and congenital hypomyelination, which are inherited demyelinating
      neuropathies characterized by different clinical severity. HMSN type II (HMSN II)
      or CMT2, the axonal form of CMT, is genetically heterogeneous. Linkage to 1p35
      p36 (CMT2A), 3q (CMT2B), and 7p (CMT2D) chromosomes has been reported in the
      disease; however, most HMSN II families do not link to any of the reported loci.
      In a large HMSN II Sardinian family, we found a missense mutation in the
      chromosome 1q MPZ gene. This Ser44Phe mutation was located in exon 2 and was
      present in the heterozygous state in all affected individuals. This is the first
      example of an HMSN II family showing an MPZ point mutation. The MPZ gene Ser44Phe
      mutation found in the HMSN II family presented in this study suggests that
      genetic analysis of HMSN II families should also include the MPZ gene, previously
      not considered to be involved in the axonal form of HMSN.

PMID- 9595995
TI  - Pilot trial of albuterol in facioscapulohumeral muscular dystrophy. FSH-DY Group.
AB  - BACKGROUND/OBJECTIVE: Facioscapulohumeral muscular dystrophy (FSHD) is currently
      untreatable, and there have been few therapeutic trials of any agent in the
      disease. Animal studies have demonstrated that beta2-adrenergic agonists induce
      muscle hypertrophy and prevent atrophy after a variety of physical and
      biochemical insults, and two human studies have shown that these agents increase
      certain measures of strength in healthy volunteers. We conducted an open-label
      pilot trial of a beta2-agonist (albuterol) in patients with FSHD. METHODS:
      Fifteen FSHD patients were given sustained-release albuterol (16.0 mg/day) for 3
      months. The primary outcome measure was lean body mass, which was assessed
      through dual energy X-ray absorptiometry (DEXA). Strength was evaluated through
      maximal voluntary isometric contraction testing (MVICT) and manual muscle
      testing. RESULTS: Albuterol significantly increased DEXA lean body mass (the
      skeletal muscle compartment) by 1.29 +/- 1.18 kg (mean +/- SD, p = 0.001).
      Strength assessed through composite MVICT scores also increased by an average of
      0.33 +/- 0.60 (p = 0.05), representing an overall 12% improvement in strength.
      CONCLUSIONS: These encouraging results suggest that beta2-agonists may have a
      role in treating FSHD and possibly other neuromuscular diseases. The effects of
      albuterol in FSHD are currently being evaluated in a larger, randomized, double
      blind, placebo-controlled trial lasting 1 year.

PMID- 9595996
TI  - Cervical rib and median sternotomy-related brachial plexopathies: a reassessment.
AB  - OBJECTIVE: The objective of this study was to identify electrodiagnostic and
      anatomic distinctions between true neurogenic thoracic outlet syndrome and median
      sternotomy-related brachial plexopathy, in reference to the pattern of
      abnormality of the medial antebrachial cutaneous sensory nerve conduction study
      (NCS) response. BACKGROUND: Neurogenic thoracic outlet syndrome and sternotomy
      related brachial plexopathy are both lower trunk brachial plexopathies, but their
      clinical and electrodiagnostic presentations are distinct. The anatomic
      differences distinguishing these disorders from each other, and from other lower
      trunk brachial plexopathies, have not been defined. METHODS: We compared the
      medial antebrachial cutaneous sensory nerve action potential amplitude with the
      median motor, ulnar motor, and ulnar sensory NCS amplitudes in 10 patients with
      neurogenic thoracic outlet syndrome and in 14 patients with sternotomy-related
      brachial plexopathy. RESULTS: In the 10 patients with neurogenic thoracic outlet
      syndrome, the medial antebrachial cutaneous amplitude was most affected, followed
      in decreasing order of involvement by the median motor, ulnar sensory, and ulnar
      motor amplitudes. Conversely, in the 14 patients with sternotomy-related brachial
      plexopathy, the ulnar sensory and motor amplitudes were the most affected
      responses. Medial antebrachial cutaneous NCS changes closely paralleled median
      motor response changes. CONCLUSIONS: The medial antebrachial cutaneous sensory
      response is sensitive in the diagnosis of neurogenic thoracic outlet syndrome.
      Our data suggest that medial antebrachial cutaneous nerve fibers are closely
      associated anatomically at the T1 root level with median motor fibers innervating
      the thenar muscles. Neurogenic thoracic outlet syndrome shows predominant damage
      in the T1 distribution, whereas sternotomy-related brachial plexopathy shows
      predominant damage in the C8 distribution, suggesting that these lesions are
      localized at the level of the anterior primary rami of the cervical roots, and
      not in the lower trunk of the brachial plexus.

PMID- 9595997
TI  - The burden, trends, and demographics of mortality from subarachnoid hemorrhage.
AB  - OBJECTIVE: The objective of this study was to describe the recent epidemiology of
      mortality from subarachnoid hemorrhage in the United States. BACKGROUND:
      Subarachnoid hemorrhage is distinct from other forms of stroke in its risk
      factors, demographics, and treatment. However, it is often clustered with other
      stroke subtypes, obscuring its unique epidemiology. METHODS: We analyzed
      subarachnoid hemorrhage mortality data from the National Center for Health
      Statistics of the United States for the years 1979 to 1994 and compared it with
      other stroke subtypes. RESULTS: Age-adjusted mortality rates of subarachnoid
      hemorrhage were 62% greater in females than in males and 57% greater in blacks
      than in whites. The median age of death from subarachnoid hemorrhage was 59 years
      compared with 73 years for intracerebral hemorrhage and 81 years for ischemic
      stroke. Mortality rates of subarachnoid hemorrhage have decreased by
      approximately 1% per year since 1979, and the mean age of death has steadily
      increased from 57 years in 1979 to 60 years in 1994. Subarachnoid hemorrhage
      accounted for 4.4% of stroke mortality but 27.3% of all stroke-related years of
      potential life lost before age 65, a measure of premature mortality. The
      proportion of years of potential life lost due to subarachnoid hemorrhage was
      comparable with ischemic stroke (38.5%) and intracranial hemorrhage (34.2%).
      CONCLUSIONS: Subarachnoid hemorrhage is an uncommon cause of stroke mortality but
      occurs at a young age, producing a relatively large burden of premature
      mortality, comparable with ischemic stroke.

PMID- 9595998
TI  - Recovery following lateral medullary infarction.
AB  - Lateral medullary infarction (LMI) has a well-defined clinical syndrome and
      vascular pathology. The functional outcome and degree of disability of patients
      with LMI, however, have not been as well investigated. We followed 18 consecutive
      patients with LMI during inpatient stroke rehabilitation. Thirteen patients were
      followed after discharge from the hospital over a mean time of 1 year. The degree
      of disability on admission and discharge from the hospital, and at follow-up was
      assessed using the motor component of the Functional Independence Measurement
      (FIM-motor). All patients were discharged home. During inpatient rehabilitation,
      the functional performance of all patients improved substantially from FIM-motor
      50.9 +/- 13.0 (mean +/- SD) on admission to 76.9 +/- 10.5 at discharge. Patients
      with lower FIM-motor scores on admission had more functional improvement from
      admission to discharge than those with higher FIM-motor scores on admission.
      Patients with disease of the posterior inferior cerebellar artery showed
      significantly less functional improvement than patients with disease of the
      vertebral artery or no identified vascular pathology in the posterior
      circulation. In the follow-up group, the FIM-motor scores further improved to
      84.6 +/- 8.4, indicating nearly full functional independence. Eighty-five percent
      were totally independent with ambulation. Five of seven previously working
      patients returned to work. Patients with LMI have few functional deficits after
      completion of inpatient rehabilitation, continue to improve functionally after
      discharge, and often resume their previous activities.

PMID- 9595999
TI  - Femoral injection of echo contrast medium may increase the sensitivity of testing
      for a patent foramen ovale.
AB  - OBJECTIVE: The diagnosis of a patent foramen ovale (PFO) as a cause of stroke is
      of increasing interest especially in young (<45 years) patients. METHODS: We
      studied potential right-to-left shunting using transesophageal echocardiography
      (TEE) and bilateral transcranial Doppler sonography (TCD) of the middle cerebral
      artery (MCA) simultaneously in 44 patients. All patients were younger than age 45
      years and suffered from an acute ischemic stroke or transient ischemic attack.
      Other possible etiologies were excluded. Echo contrast medium was injected in an
      alternating mode via antecubital or femoral veins. Tests were performed with and
      without the Valsalva maneuver. The criteria for a PFO were that the contrast pass
      from the right to the left atrium (TEE) and early detection (<10 seconds) of more
      than 10 micro air bubbles in at least one MCA by TCD. RESULTS: A PFO was
      diagnosed in 22 patients (50%). The detection rate with TEE/TCD was 11.4%/4.5%
      via antecubital injection, 18%/13.6% via antecubital injection plus the Valsalva
      maneuver, 38.6%/36% via femoral injection alone, and 50%/50% via femoral
      injection plus the Valsalva maneuver. The difference between femoral and
      antecubital injections was significant with and without the Valsalva maneuver (p
      < 0.01, chi2 test). There were no differences between TEE and TCD after femoral
      injection with the Valsalva maneuver. The brain transit time was 4.6 +/- 2.1
      seconds for femoral injection and 6.3 +/- 4.1 seconds for antecubital injection.
      CONCLUSIONS: The sensitivity in detecting a PFO was markedly increased by femoral
      injection. This may be caused by different inflow patterns to the right atrium:
      inferior vena caval flow is directed to the right atrial septum, whereas superior
      vena caval flow is directed to the tricuspid valve. Thus, femoral injection may
      help to improve the detection of PFO and may explain the differences between TEE
      and TCD findings in previous studies.

PMID- 9596000
TI  - Familial typical migraine: linkage to chromosome 19p13 and evidence for genetic
      heterogeneity.
AB  - Migraine is a frequent familial disorder that, in common with most multifactorial
      disorders, has an unknown etiology. The authors identified several families with
      multiple individuals affected by typical migraine using a single set of
      diagnostic criteria and studied these families for cosegregation between the
      disorder and markers on chromosome 19, the location of a mutation that causes a
      rare form of familial hemiplegic migraine (FHM). One large tested family showed
      both cosegregation and significant allele sharing for markers situated within or
      adjacent to the FHM locus. Multipoint GENEHUNTER results indicated significant
      excess allele sharing across a 12.6-cM region containing the FHM Ca2+ channel
      gene, CACNL1A4 (maximum nonparametric linkage Z score = 6.64, p = 0.0026), with a
      maximum parametric lod score of 1.92 obtained for a (CAG)n triplet repeat
      polymorphism situated in exon 47 of this gene. The CAG expansion did not,
      however, appear to be the cause of migraine in this pedigree. Other tested
      families showed neither cosegregation nor excess allele sharing to chromosome 19
      markers. HOMOG analysis indicated heterogeneity, generating a maximum HLOD score
      of 3.6. It was concluded that Chr19 mutations either in the CACNL1A4 gene or a
      closely linked gene are implicated in some pedigrees with familial typical
      migraine, and that the disorder is genetically heterogeneous.

PMID- 9596001
TI  - Role of anticardiolipin antibodies in young persons with migraine and transient
      focal neurologic events: a prospective study.
AB  - Anticardiolipin antibodies (aCL) are a risk factor for cerebral ischemia. In
      migraine, the association is controversial, with widely varying results in
      different small series. The controversy in part may be due to the inherent
      difficulty in distinguishing the transient focal neurologic events (TFNE) of
      migraine from TIA. To assess the frequency of aCL in migraine, we prospectively
      evaluated consecutive adults under 60 years of age with migraine without aura and
      with recent TFNE (<24-hour duration) clinically suggestive of either migraine
      with aura or TIA. We concomitantly enrolled persons with no CNS disease. Each
      person was interviewed and had blood drawn for solid-phase ELISA with IgG and IgM
      aCL isotyping. Neuroradiologic studies were reviewed. Patients with TFNE were
      followed every 6 months for the duration of the 3-year study. The frequency of
      aCL positivity (IgG >20, IgG >40, IgM >7.5) for the 645 patients with TFNE (8.8,
      3.1, 4.2%), the 518 persons in the TFNE subgroup with migraine with aura (8.9,
      3.3, 4.1%), the 497 persons with migraine without aura (7.0, 2.0, 3.6%), and the
      366 control subjects (9.3, 3.6, 3.9%) did not differ significantly between
      groups. In TFNE patients with elevated aCL titer, the association was positive
      with diabetes mellitus, TFNE duration <15 minutes, and diplopia and was negative
      with hemiparesis, tinnitus, and family history of stroke. Findings on imaging
      consistent with cerebral ischemia were more frequent in aCL-positive persons. The
      short-term risk of stroke was uniformly low. In young persons, aCL is not
      associated with migraine or with TFNE, although diabetes mellitus, negative
      family history of stroke, and brief duration of symptoms (including diplopia) may
      predict immunoreactivity. Imaging studies suggest an ischemic etiology of TFNE in
      this cohort.

PMID- 9596002
TI  - Early neurologic complications following allogeneic bone marrow transplant for
      leukemia: a prospective study.
AB  - BACKGROUND: Bone marrow transplant (BMT) is used for both neoplastic and
      nonneoplastic diseases. Following BMT, particularly during the first 3 months,
      patients have a number of neurologic complications. We evaluated the early
      neurologic complications following BMT and their influence on survival. METHODS:
      We prospectively followed 115 consecutive patients having BMT for leukemia, for a
      median period of 90 days after transplantation. RESULTS: Sixty-four patients
      (56%) had neurologic complications. Sixteen developed more than one complication.
      Twenty-seven patients (25%) had major neurologic complications: metabolic
      encephalopathy (8), seizures (8), psychiatric symptoms (3), cerebral hemorrhage
      (1), cerebral abscess (1), leukemic meningitis (1), peripheral neuropathies (5),
      and myopathies (2). Forty patients (35%) had minor complications, including
      headache (16) and tremor (31). Major neurologic complications occurred after
      engraftment in most patients. Metabolic encephalopathy correlated with graft
      versus-host disease (GVHD) (p < 0.03). Seven percent of patients had generalized
      seizures that occurred without signs of structural cerebral lesions. Probability
      of survival at day 90 was lower in patients with than in those without major
      central nervous system complications (63% versus 87.5%, p < 0.01). CONCLUSIONS:
      Neurologic complications are frequent during the first 3 months following BMT and
      affect patient survival. Drug neurotoxicity and acute GVHD are the main factors
      influencing their occurrence.

PMID- 9596003
TI  - Bright light suppresses melatonin in blind patients with neuronal ceroid
      lipofuscinoses.
AB  - We studied whether light information can reach the pineal glands of clinically
      blind patients with neuronal ceroid-lipofuscinoses. The suppression of melatonin
      by light was used as an indicator. Seven patients and seven control subjects were
      exposed to 3,000-lux light for 60 minutes at the rising phase of the melatonin
      synthesis. Most patients were not cooperative, and their eyelids were opened by a
      researcher every 2 minutes for 2 seconds. The control subjects opened and closed
      their eyes similarly by themselves. Light suppressed melatonin in three of seven
      control subjects and in all patients. The average postlight levels were 80%
      (control subjects) and 51% (patients) of the corresponding levels during the dim
      light session. Despite degenerated retinas of the blind patients, light can
      penetrate their visual system to the hypothalamic and pineal levels and regulate
      neuroendocrine function.

PMID- 9596004
TI  - Georges Guillain's neurologic exploration of America.
AB  - This is a study of the status of American neurology at the beginning of the 20th
      century as perceived by European neurologist Georges Guillain. Guillain trained
      in Paris, the international "Mecca" of neurology at that time. Whereas many
      Americans traveled and studied in Europe, very few European neurologists made the
      reverse journey to the United States. In 1902 Georges Guillain, age 26, traveled
      to the United States with the specific aim of evaluating neurologic services in
      America. Recent access to Guillain's personal travel journal and an article in
      French that he wrote after his return to Europe provide first-hand documentation
      of American neurology at the turn of the century from a European perspective.
      Using introductory references from his teacher, Pierre Marie, Guillain visited
      New York, Chicago, Boston, Philadelphia, and Baltimore. He studied hospitals,
      outpatient departments, laboratories, and universities, comparing them with
      institutions in his native France and other European capitals. Guillain was
      particularly struck by the creative energy of American neurologists, the broad
      ranging programs in research and patient care, and the strong financial support
      provided by local philanthropists, universities, and governments. Guillain
      clearly foresaw the rising international role of American neurology and the
      prominence it would gain by the end of his career in the 1950s.

PMID- 9596005
TI  - Acute delirium after withdrawal of amantadine in Parkinson's disease.
AB  - We present three patients who, after long-term therapy with amantadine (4 to 18
      years), experienced an acute delirium with confusion, disorientation, agitation,
      and paranoia on withdrawal. These patients had Parkinson's disease for 5 to 29
      years; mean age was 73 years. All had a history of varying degrees of dementia
      and transient hallucinations in the past. Adjustment of other medications was
      ineffective in improving their condition and no other cause was found. Only with
      reinstitution of amantadine did the patients return to baseline status (usually
      within days).

PMID- 9596006
TI  - A genetic polymorphism of MAO-B modifies the association of cigarette smoking and
      Parkinson's disease.
AB  - In a population-based case-control study, we found a reversal of the association
      of cigarette smoking with Parkinson's disease (PD) in relation to the monoamine
      oxidase B intron 13 genetic polymorphism. A reduced PD risk related to pack-years
      of smoking was detected for persons with the G allele, whereas an opposite effect
      was found among persons with the A allele. These results indicate an unexplained
      interaction between cigarette smoking and this genetic polymorphism.

PMID- 9596007
TI  - Long-term effect of botulinum toxin on impairment and functional health in
      cervical dystonia.
AB  - We investigated the long-term effect of botulinum toxin type A (BTA) on
      impairment as well as functional health in terms of disability, handicap, and
      quality of life in 64 patients with cervical dystonia. These patients, who first
      participated in a double-blind trial, were followed for another 12 months. Fifty
      four patients continued treatment after 12 months of follow-up and showed
      improvement on all scales. Furthermore, this effectiveness appeared to increase
      during follow-up, which suggests a cumulative clinical effect of BTA.

PMID- 9596008
TI  - A radioimmuno-precipitation assay for antibodies to botulinum A.
AB  - We quantified antibodies to botulinum A (anti-BTx) by immunoprecipitation of 125I
      BTx. We tested seven bioassay-positive sera and 68 coded samples, including 18
      from patients who had ceased to respond to BTx treatment. Compared with values
      from healthy control subjects and 42 neurologic control subjects, all bioassay
      positive sera were positive (range, 258 to 2,809 pM) and 49 of 50 patients who
      continued to respond to BTx were negative (<130 pM). This simple, specific,
      sensitive, and quantitative assay should prove helpful in the investigation of
      BTx resistance.

PMID- 9596009
TI  - Agyria-pachygyria and agenesis of the corpus callosum: autosomal recessive
      inheritance with neonatal death.
AB  - We report three neonates, one boy and two girls, born to an inbred Arab family
      who had cortical dysplasia, probably agyria-pachygyria, and agenesis of the
      corpus callosum. All had asphyxia, intractable seizures, and increased muscle
      tone at birth and died in the neonatal period. Congenital microcephaly or
      dysmorphic features were absent. Cytogenetic abnormality, metabolic disorder, and
      intrauterine infection were excluded. These cases suggest a new cerebral
      dysgenesis syndrome with autosomal recessive inheritance.

PMID- 9596010
TI  - Epileptic skew deviation.
AB  - We describe a 43-year-old neurologically intact patient who reported episodes of
      diplopia and oscillopsia associated with a right-beating nystagmus and a skew
      deviation. These symptoms and signs were related to a left posterior epileptic
      EEG discharge. We suggest that these ocular motor signs derived from an ictal
      activation of the vestibular cortex, which in turn activated descending
      projections to the vestibular nuclei, leading to both a dynamic (right-beating
      nystagmus) and a static (skew deviation) vestibular imbalance.

PMID- 9596011
TI  - Epileptic pseudodementia.
AB  - Dementia is a frequent cause of memory loss with aging. The incidence of complex
      partial seizures sharply rises after age 60. Complex partial seizures that occur
      with subtle clinical signs or loss of awareness, or occur during sleep may defy
      identification. We report five elderly patients fearing dementia in whom memory
      dysfunction was due to unrecognized complex partial seizures.

PMID- 9596012
TI  - Carbamazepine responsive epileptic oral motor and ocular motor apraxia.
AB  - We evaluated seven patients with oral motor apraxia and ocular motor apraxia.
      Apraxia in three patients (Group 1) with new-onset partial seizures and
      epileptiform discharges on EEG improved with carbamazepine. Four patients (Group
      2) without seizures and nonepileptiform EEG findings had no change in apraxia
      after a trial of carbamazepine. Epileptic apraxia may precede clinical seizures
      and can respond to antiepileptic drugs.

PMID- 9596013
TI  - Congenital muscular dystrophy and cerebellar atrophy.
AB  - Two siblings and two other unrelated patients had congenital muscular weakness
      and dystrophic changes but normal immunocytochemical stainings for merosin,
      dystrophin, and dystrophin-related proteins on muscle biopsy. All had marked
      ataxia and cerebellar atrophy or hypoplasia. Cerebral white matter and cortical
      organization appeared normal.

PMID- 9596014
TI  - Deterioration of multifocal motor neuropathy after plasma exchange.
AB  - We report a patient with motor neuropathy in whom plasma exchange (PE) was
      followed by a pronounced clinical worsening with the appearance of conduction
      blocks in previously clinically unaffected motor nerves, leading to the diagnosis
      of multifocal motor neuropathy (MMN). This report highlights the different
      response to therapy of MMN and chronic inflammatory demyelinating polyneuropathy
      (CIDP) because not only steroids but also PE, which is often effective in CIDP,
      do not improve and at times may even worsen MMN.

PMID- 9596015
TI  - Antibodies to ion-channel proteins in thymoma with myasthenia, neuromyotonia, and
      peripheral neuropathy.
AB  - A patient presented with anti-acetylcholine receptor antibody-positive myasthenia
      gravis. After removal of a thymoma and use of cytotoxic therapy, there was
      worsening of myasthenia, onset of muscle stiffness and hyperexcitability, and
      electrophysiologic signs of peripheral neuropathy. Elevated serum titers of
      antibodies to neuronal voltage-gated K+ channels were present, consistent with
      neuromyotonia (Isaacs' syndrome). A beneficial response to treatment paralleled
      changes in antibody titers.

PMID- 9596016
TI  - Calcification in the basal ganglia with chronic active Epstein-Barr virus
      infection.
AB  - We report three Japanese children with chronic active Epstein-Barr virus (EBV)
      infection and neurologic findings that included symmetric calcifications in the
      bilateral basal ganglia. This finding, common in pediatric acquired
      immunodeficiency syndrome (AIDS), suggests that EBV could be responsible for
      calcification in the basal ganglia seen in children with AIDS and in other
      idiopathic diseases.

PMID- 9596017
TI  - Early anticoagulation in patients with prosthetic heart valves and intracerebral
      hematoma.
AB  - Anticoagulants are generally contraindicated in patients with intracerebral
      hematoma. However, in patients with prosthetic heart valves it may be dangerous
      to withhold such therapy because of possible thromboembolic complications. We
      treated four such patients with i.v. heparin starting early after the hemorrhage.
      The hematomas receded in all patients according to the follow-up CTs, and none
      had thromboembolic disorders. Three patients had good outcomes, and one remained
      in a persistent vegetative state after an event of acute pulmonary edema.

PMID- 9596018
TI  - Neurologists' attitudes regarding rt-PA for acute ischemic stroke.
AB  - We studied the attitudes of 238 Texas neurologists regarding the use of
      recombinant tissue plasminogen activator (rt-PA). The results show that 38 (16%)
      had treated stroke patients with rt-PA, and 97% of these would do so again. In
      the group that had not treated patients, 60% would treat if a suitable candidate
      presented. We conclude that soon after FDA approval of rt-PA, two-thirds of
      survey respondents were using or were planning to use this therapy. Those
      neurologists who have used rt-PA for stroke report a positive experience.

PMID- 9596019
TI  - Childhood onset of benign positional vertigo.
AB  - Benign positional vertigo (BPV) rarely occurs in children, but we identified
      three members of a family who developed BPV before age 13 years. All three had
      migraine headaches and two had spontaneous episodes of vertigo. Vasospasm
      associated with migraine possibly resulted in ischemic damage to the utricular
      macule, leading to the development of BPV in these patients.

PMID- 9596020
TI  - Motor slowing precedes cognitive impairment in the oldest old.
AB  - Eighty-five healthy elderly subjects were prospectively evaluated for 3 years to
      determine motor differences between those who remain cognitively intact and those
      who developed cognitive impairment during prospective follow-up. The 18 subjects
      who developed cognitive impairment had slower finger tapping and took longer to
      walk 30 feet before or at the time of cognitive impairment. Coordination was more
      impaired and steps, but not balance, deteriorated more rapidly, independent of
      other variables.

PMID- 9596021
TI  - Lack of relation between race and cognitive test performance in Alzheimer's
      disease.
AB  - This study evaluated cognitive test performance in African-American and European
      American Alzheimer's disease patients with equivalent years of education. Group
      differences were negligible on a variety of memory, language, and attentional
      measures, including several widely used neuropsychological tests. Differences
      between racial groups observed in earlier studies may have stemmed, in part, from
      differences in education, which may itself serve as a proxy for other potentially
      important sociologic and health variables.

PMID- 9596022
TI  - Relative stability of a minimal CTG repeat expansion in a large kindred with
      myotonic dystrophy.
AB  - The genetic basis for myotonic dystrophy (DM) is a CTG trinucleotide repeat
      expansion. The number of CTG repeats commonly increases in affected individuals
      of successive generations, in association with anticipation. We identified a
      large DM family in which multiple members had minimal CTG repeat expansions, and
      in which the number of CTG repeats remained in the minimally expanded range
      through at least three, and possibly four, generations. This relative stability
      of minimal CTG repeat expansions may help to maintain the DM mutation in the
      population.

PMID- 9596023
TI  - Acetazolamide-responsive migraine in CADASIL.

PMID- 9596024
TI  - Cervical myelopathy caused by Whipple's disease.

PMID- 9596025
TI  - Syndrome of continuous muscle fiber activity in a human immunodeficiency virus
      infected patient.

PMID- 9596026
TI  - Acquired abducens-trigeminal synkinesis.

PMID- 9596027
TI  - Spurious familial dystonia.

PMID- 9596028
TI  - Drug-induced pseudolymphoma secondary to lamotrigine.

PMID- 9596029
TI  - Pituitary apoplexy presenting as a thunderclap headache.

PMID- 9596030
TI  - Moriatic aphasia: a syndrome of acute carotid occlusion on the dominant side.

PMID- 9596031
TI  - Chronic relapsing axonal neuropathy responsive to intravenous immunoglobulin.

PMID- 9596032
TI  - 'Sleep benefit' in Parkinson's disease.

PMID- 9596033
TI  - EEG findings in patients with hippocampal atrophy.

PMID- 9596034
TI  - The Alzheimer's disease assessment scale.

PMID- 9596035
TI  - Do neurologists have a future in neuroimaging?

PMID- 9596036
TI  - Causes of perimesencephalic nonaneurysmal subarachnoid hemorrhage.

PMID- 9596037
TI  - EEG in anti-epileptic drug withdrawal in partial epilepsies.

PMID- 9596039
TI  - Change in the Department of Veterans Affairs.

PMID- 9596038
TI  - Intracranial hemorrhage associated with cocaine abuse.

PMID- 9596040
TI  - Central poststroke pain and Wallenberg's lateral medullary infarction.

PMID- 9596042
TI  - New evidence on the violence risk posed by people with mental illness: on the
      importance of specifying the timing and the targets of violence.

PMID- 9596041
TI  - Violence by people discharged from acute psychiatric inpatient facilities and by
      others in the same neighborhoods.
AB  - BACKGROUND: The public perception that mental disorder is strongly associated
      with violence drives both legal policy (eg, civil commitment) and social practice
      (eg, stigma) toward people with mental disorders. This study describes and
      characterizes the prevalence of community violence in a sample of people
      discharged from acute psychiatric facilities at 3 sites. At one site, a
      comparison group of other residents in the same neighborhoods was also assessed.
      METHODS: We enrolled 1136 male and female patients with mental disorders between
      the ages of 18 and 40 years in a study that monitored violence to others every 10
      weeks during their first year after discharge from the hospital. Patient self
      reports were augmented by reports from collateral informants and by police and
      hospital records. The comparison group consisted of 519 people living in the
      neighborhoods in which the patients resided after hospital discharge. They were
      interviewed once about violence in the past 10 weeks. RESULTS: There was no
      significant difference between the prevalence of violence by patients without
      symptoms of substance abuse and the prevalence of violence by others living in
      the same neighborhoods who were also without symptoms of substance abuse.
      Substance abuse symptoms significantly raised the rate of violence in both the
      patient and the comparison groups, and a higher portion of patients than of
      others in their neighborhoods reported symptoms of substance abuse. Violence in
      both patient and comparison groups was most frequently targeted at family members
      and friends, and most often took place at home. CONCLUSIONS: "Discharged mental
      patients" do not form a homogeneous group in relation to violence in the
      community. The prevalence of community violence by people discharged from acute
      psychiatric facilities varies considerably according to diagnosis and,
      particularly, co-occurring substance abuse diagnosis or symptoms.

PMID- 9596043
TI  - Sex differences in the prevalence and detection of depressive and anxiety
      disorders in general health care settings: report from the World Health
      Organization Collaborative Study on Psychological Problems in General Health
      Care.
AB  - BACKGROUND: Understanding the relevance of biological and social factors to sex
      differences in the prevalence and detection of depressive and anxiety disorders
      has been impaired by the lack of standardized research methods across cultures.
      METHOD: Prevalence rates of depressive and anxiety disorders were assessed using
      a 2-stage design from 26,969 patients attending for primary care in 15 centers
      from 4 continents. Logistic regression analysis was used to examine sex
      differences in prevalence and detection across centers. RESULTS: Odds ratios for
      women compared with men of current depression (1.60; 95% confidence interval
      [CI], 1.37-1.86) and agoraphobia or panic (1.63; 95% CI, 1.18-2.20) were
      consistent across centers. The odds ratio for generalized anxiety varied among
      centers: 3 groups of centers were identified with odds ratios of 0.46 (95% CI,
      0.27-0.78), 1.34 (95% CI, 1.08-1.66), and 3.09 (95% CI, 1.60-5.89). There was no
      sex difference in the detection of depressive and anxiety disorders by physicians
      across centers. CONCLUSIONS: The absence of a sex-by-center effect for current
      depression and agoraphobia or panic disorder is consistent with biological and
      psychosocial factors, either interacting or working alone, that have a similar
      final effect across cultures. It does not support the idea that sex differences
      in prevalence are caused by local psychosocial factors that vary from country to
      country. The variation in the odds ratio for generalized anxiety disorder offers
      some support to the idea that there are local differences between the centers
      contributing to the sex difference in rates. Patients' sex does not appear to
      affect the likelihood of current depression and anxiety being detected by primary
      care physicians.

PMID- 9596044
TI  - Neuropsychological deficits in obsessive-compulsive disorder: a comparison with
      unipolar depression, panic disorder, and normal controls.
AB  - BACKGROUND: The neuropsychological dysfunction associated with obsessive
      compulsive disorder (OCD) has similarities to the deficits reported in other
      affective or anxiety disorders. We directly compared cognitive function in
      patients with OCD with that in matched patients with unipolar depression and
      panic disorder and healthy control subjects to establish the specific nature of
      neuropsychological deficits in OCD. METHODS: Thirty patients with OCD, 30
      patients with panic disorder, 20 patients with unipolar depression, and 30
      controls completed a computerized neuropsychological battery that assessed the
      accuracy and latency of executive, visual memory, and attentional functions.
      RESULTS: The groups did not differ according to age, years of education, or
      estimated IQ. However, we found group differences in cognitive performance. The
      patients with OCD were impaired on measures of spatial working memory, spatial
      recognition, and motor initiation and execution. In contrast, performance of
      these tasks by patients with panic disorder or depression did not differ from
      that of controls. There were no group differences for performance on the measures
      of planning, cognitive speed, pattern recognition, and delayed matching to
      sample, although patients with depression were impaired for attentional set
      shifting. CONCLUSIONS: Neuropsychological deficits were observed in patients with
      OCD that were not observed in matched patients with panic disorder or unipolar
      depression. As such, the cognitive dysfunction in OCD appears to be related to
      the specific illness processes associated with the disorder.

PMID- 9596045
TI  - Risk factors for binge eating disorder: a community-based, case-control study.
AB  - BACKGROUND: Many risk factors have been implicated for eating disorders, although
      little is known about those for binge eating disorder. METHODS: A community
      based, case-control design was used to compare 52 women with binge eating
      disorder, 104 without an eating disorder, 102 with other psychiatric disorders,
      and 102 with bulimia nervosa. RESULTS: The main risk factors identified from the
      comparison of subjects with binge eating disorder with healthy control subjects
      were certain adverse childhood experiences, parental depression, vulnerability to
      obesity, and repeated exposure to negative comments about shape, weight, and
      eating. Compared with the subjects with other psychiatric disorders, those with
      binge eating disorder reported more childhood obesity and more exposure to
      negative comments about shape, weight, and eating. Certain childhood traits and
      pronounced vulnerability to obesity distinguished the subjects with bulimia
      nervosa from those with binge eating disorder. CONCLUSIONS: Binge eating disorder
      appears to be associated with exposure to risk factors for psychiatric disorder
      and for obesity. When compared with the wide range of risk factors for bulimia
      nervosa, the risk factors for binge eating disorder are weaker and more
      circumscribed. Pre-morbid perfectionism, negative self-evaluation, and
      vulnerability to obesity appear especially to characterize those in whom bulimia
      nervosa subsequently develops.

PMID- 9596046
TI  - Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance
      imaging: a meta-analytic study.
AB  - BACKGROUND: Although many quantitative magnetic resonance imaging studies have
      found significant volume reductions in the hippocampi of patients with
      schizophrenia compared with those of normal control subjects, others have not.
      Therefore, the issue of hippocampal volume differences associated with
      schizophrenia remains in question. METHODS: Two meta-analyses were conducted to
      reduce the potential effects of sampling error and methodological differences in
      data acquisition and analysis. Eighteen studies with a total patient number of
      522 and a total control number of 426 met the initial selection criteria.
      RESULTS: Meta-analysis 1 yielded mean effect sizes of 0.37 (P<.001) for the left
      hippocampus and 0.39 (P<.001) for the right, corresponding to a bilateral
      reduction of 4%. Meta-analysis 2 indicated that the inclusion of the amygdala in
      the region of interest significantly increased effect sizes across studies
      (effect size for the left hippocampus and amygdala, 0.67; for the right, 0.72),
      whereas variables such as illness duration, total slice width, magnet strength,
      the use of the intracranial volume as a covariate, measurement reliability, and
      study quality did not. No laterality differences were observed in these data.
      CONCLUSIONS: Schizophrenia is associated with a bilateral volumetric reduction of
      the hippocampus and probably of the amygdala as well. These findings reinforce
      the importance of the medial temporal region in schizophrenia and are consistent
      with frequently reported memory deficits in these patients. Future quantitative
      magnetic resonance imaging studies evaluating the hippocampal volume should
      measure the hippocampus and amygdala separately and compare the volumetric
      reduction in these structures to that observed in other gray matter areas.

PMID- 9596047
TI  - Delta sleep deficits in schizophrenia: evidence from automated analyses of sleep
      data.
AB  - BACKGROUND: Several, though not all, polysomnographic studies that use
      conventional visual scoring techniques show delta sleep deficits in
      schizophrenia. Delta sleep (in particular, > or = 1- to 2-Hz frequency range),
      mediated by thalamocortical circuits, is postulated to be abnormal in
      schizophrenia. We investigated whether deficits in delta sleep occur in
      schizophrenia and whether these are primarily related to the illness or are
      epiphenomena of previous medication use or illness chronicity. METHODS: We
      compared 30 unmedicated schizophrenic patients and 30 age- and sex-matched
      controls for sleep data evaluated by visual scoring as well as automated period
      amplitude analyses and power spectral analyses. RESULTS: Schizophrenic patients
      had reduced visually scored delta sleep. Period amplitude analyses showed
      significant reductions in delta wave counts but not rapid eye movement counts;
      power spectral analyses showed reductions in delta as well as theta power. Delta
      spectral power was also reduced in the subset of 19 neuroleptic-naive, first
      episode schizophrenic patients compared with matched controls. Delta deficits
      were more pronounced in the greater than 1- to 2-Hz frequency range. CONCLUSIONS:
      Delta sleep deficits that occur in schizophrenia may be related to the primary
      pathophysiological characteristics of the illness and may not be secondary to
      previous neuroleptic use. Automated sleep quantification by means of period
      amplitude and power spectral analyses can complement the use of conventional
      visual scoring for understanding electrophysiological abnormalities in
      psychiatric disorders.

PMID- 9596048
TI  - Treatment of depressive symptoms in human immunodeficiency virus-positive
      patients.
AB  - BACKGROUND: This randomized clinical trial compared 16-week interventions with
      interpersonal psychotherapy, cognitive behavioral therapy, supportive
      psychotherapy, and supportive psychotherapy with imipramine for human
      immunodeficiency virus (HIV)-positive patients with depressive symptoms. METHODS:
      Subjects (N = 101; 85 male, 16 female) with known HIV seropositivity for at least
      6 months were randomized to 16 weeks of treatment. Inclusion criteria were 24
      item Hamilton Depression Rating Scale score of 15 or higher, clinical judgment of
      depression, and physical health sufficient to attend outpatient sessions.
      Therapists were trained in manualized therapies specific for HIV-positive
      patients. Treatment adherence was monitored. RESULTS: Subjects randomized to
      interpersonal psychotherapy (n = 24) and supportive psychotherapy with imipramine
      (n = 26) had significantly greater improvement on depressive measures than those
      receiving supportive psychotherapy (n = 24) or cognitive behavioral therapy (n =
      27). Similar results appeared in the completer subsample. CONCLUSIONS: Depressive
      symptoms appear treatable in HIV-positive patients. Interpersonal psychotherapy
      may have particular advantages as a psychotherapy for patients who have
      experienced the significant life events of HIV infection.

PMID- 9596049
TI  - Cost-effectiveness of intensive psychiatric community care for high users of
      inpatient services.
AB  - BACKGROUND: This 2-year experimental study evaluated the effectiveness and cost
      of 10 intensive psychiatric community care (IPCC) programs at Department of
      Veterans Affairs medical centers in the northeastern United States. METHODS: High
      users of inpatient services were randomly assigned to either IPCC or standard
      Department of Veterans Affairs care at 6 general medical and surgical hospitals
      (n=271 vs 257) and 4 neuropsychiatric hospitals (n=183 vs 162). Patient
      interviews every 6 months and national computerized data were used to assess
      clinical outcomes, health service use, health care costs, and non-health care
      costs. RESULTS: There was only 1 significant clinical difference between groups
      across follow-up periods: IPCC patients at general medical and surgical sites had
      higher community living skills. However, at the final interview, IPCC patients at
      general medical and surgical sites showed significantly lower symptoms, higher
      functioning, and greater satisfaction with services. Treatment with IPCC
      significantly reduced hospital use only at neuropsychiatric sites (320 vs 513
      days, P<.001). Total societal costs, including the cost of IPCC, were lower for
      IPCC at neuropsychiatric sites ($82,454 vs $116,651, P<.001), but greater at
      general medical and surgical sites ($51,537 vs $46,491, P<.01). When 2 sites that
      incompletely implemented the model were dropped from the analysis, costs at
      general medical and surgical sites were $38 lower for IPCC (P=.26). CONCLUSIONS:
      At acute care hospitals, IPCC treatment is associated with greater long-term
      clinical improvement and, when fully implemented, is cost-neutral. At long-stay
      hospitals treating older, less-functional patients, it is not associated with
      clinical or functional improvement but generates substantial cost savings.
      Intensive psychiatric community care thus has beneficial, but somewhat different,
      outcome profiles at different types of hospitals.

PMID- 9596050
TI  - A registry-based twin study of depression in men.
AB  - BACKGROUND: The only large, registry-based twin study of depression using
      diagnostic criteria assessed by structured interview included only women. We
      present results from a comparable study of men. METHODS: Data were collected
      using a standardized telephone interview of men from the Vietnam Era Twin
      Registry. Both twins from 3372 pairs participated. Proband-wise concordance rates
      and biometric modeling were used to analyze the data. RESULTS: The diagnosis of
      major depression (MD), as defined by DSM-III-R, and the subtype of
      severe/psychotic MD were significantly affected by genetic (h2=0.36 and 0.39,
      respectively) and nonshared environmental (e2=0.64 and 0.61, respectively)
      factors but not by family environmental factors. Dysthymia and mild and moderate
      MD were affected by family environmental (c2=0.27, 0.08, and 0.14, respectively)
      and nonshared environmental (e2=0.73, 0.92, and 0.86, respectively) factors but
      not by genetic factors. Early-onset (before age 30 years) and late-onset (after
      age 30 years) MD were significantly affected by genetic (h2=0.47 and 0.10,
      respectively) and nonshared environmental (e2=0.53 and 0.90, respectively)
      factors. Early-onset MD was significantly more heritable than late-onset MD.
      CONCLUSIONS: The magnitude of genetic and environmental effects on depression in
      men is similar to that previously reported in women. Also similar to previous
      findings, more severe and earlier-onset depression may be more strongly affected
      by genetic factors, but differences in the reliability of reports of depression
      associated with severity may inflate estimates of the effect of the unique
      environment and deflate heritability estimates for less severe depression.

PMID- 9596051
TI  - Cerebrospinal fluid concentrations of somatostatin and biogenic amines in grown
      primates reared by mothers exposed to manipulated foraging conditions.
AB  - BACKGROUND: In an earlier study, infant primates were nursed by mothers randomly
      assigned to variable foraging demand (VFD) or nonvariable foraging conditions
      (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of
      cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentrations
      and decreased CSF cortisol levels vs non-VFD counterparts. To further
      characterize neurobiological sequelae of disturbed early rearing, CSF
      concentrations of serotonin, dopamine, and norepinephrine metabolites (5
      hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4
      hydroxyphenethyleneglycol [MHPG], respectively) and of somatostatin were
      determined. METHODS: Second CSF taps were obtained from the previously studied
      cohort of 30 subjects and from 28 age-matched ad libitum-reared control subjects.
      Relevant assays were performed. RESULTS: All neurochemicals assayed except MHPG
      were elevated in the VFD-reared compared with non-VFD subjects. In the VFD group,
      statistically significant positive correlations between corticotropin-releasing
      factor and each neurochemical was found, except for MHPG. In the non-VFD
      subjects, no significant correlations with corticotropin-releasing factor were
      observed. No effect of age was evident. CONCLUSIONS: Reducing the predictability
      of maternal foraging demand during early rearing was associated with elevations
      of cisternal somatostatin and of serotonin and dopamine metabolite concentrations
      in grown offspring. The corticotropin-releasing factor elevations reported
      previously were positively correlated with all the elevated CSF parameters of the
      current study. The findings support the notion that adverse early rearing
      experiences in primates have longstanding and complex effects on a range of
      neurochemicals relevant to emotional regulation. Replication in prospective age
      controlled studies is warranted.

PMID- 9596052
TI  - Continuous quality improvement and primary care.

PMID- 9596053
TI  - The Robert Wood Johnson Foundation.

PMID- 9596054
TI  - Continuous quality improvement in primary care: what's happening?
AB  - OBJECTIVES: Despite much health care interest in quality and Continuous Quality
      Improvement, there is little quantitative information about it. The purpose of
      this study was to measure the attitudes, activities, and organizational cultures
      concerning Continuous Quality Improvement in a group of Midwestern primary care
      clinics. METHODS: Three surveys of the clinicians, nurses, and other staff in 44
      primary care clinics in the metropolitan area of Minneapolis and St. Paul were
      conducted. These surveys assessed: (1) attitudes about quality improvement, (2)
      previous efforts in these clinics to use process improvement teams, and (3) the
      extent to which the clinics' organizational cultures were perceived as supporting
      quality. The Provider Attitude Survey was completed by clinicians and nurses; the
      Process Improvement Progress was completed by members of the best Continuous
      Quality Improvement teams, if any; and the Quality Systems Inventory was
      completed by all personnel. RESULTS: Most of the clinical personnel reported
      support for various Continuous Quality Improvement concepts, but their
      understanding and experience were limited. Only 20 (45%) clinics had had at least
      one Continuous Quality Improvement team in the past, only five of the 12 teams
      with adequate information had completed an improvement cycle, and only seven
      reported improving a process with it. The mean clinic scores for quality culture
      were no better than those in other types of organizations. CONCLUSIONS: Despite
      relatively favorable attitudes and some Continuous Quality Improvement
      activities, there appears to be a need to help clinics build skill and experience
      for the required care improvements.

PMID- 9596055
TI  - Type of health care coverage and the likelihood of being screened for cancer.
AB  - OBJECTIVES: This study explored whether type of outpatient health coverage
      affected the likelihood of men and women aged 20 to 64 years receiving
      recommended cancer screening procedures. METHODS: Data from the 1989 and 1990
      California Behavioral Risk Factor Surveillance Surveys were used to compare Pap
      smear, mammogram, fecal occult blood test, and proctoscopic examination rates for
      adults with three different types of private health care coverage (Group/staff
      model health maintenance organization, Independent Practice Association Model
      health maintenance organization, indemnity plan) and no outpatient health
      insurance. Logistic regression models were used to control for sociodemographic
      and health characteristics and whether individuals had a usual health care
      provider. RESULTS: Individuals with Group Model health maintenance organization
      coverage were significantly more likely than those with indemnity plans to have
      had recent cervical, breast, and colorectal cancer screening, whereas screening
      likelihood for those with Independent Practice Association model health
      maintenance organization coverage did not differ substantially from those with
      indemnity plans. Individuals with no outpatient coverage were less likely to be
      screened than those with outpatient coverage. The most consistently significant
      predictor across cancer screening procedures for both men and women was having a
      usual doctor who knew their medical history. CONCLUSIONS: Adults who had private
      outpatient insurance were more likely to undergo recommended cancer detection
      procedures than those who did not. Adults who belonged to a health maintenance
      organization, which emphasizes and pays for a broader spectrum preventive care,
      were more likely to receive Pap smears, mammograms, and fecal occult blood tests
      than those covered by indemnity plans. Receiving care primarily from one doctor
      significantly increased the likelihood of having screening procedures,
      irrespective of type of health plan.

PMID- 9596056
TI  - Influence of the NIH Consensus Conference on Helicobacter pylori on physician
      prescribing among a Medicaid population.
AB  - OBJECTIVES: In February 1994, an National Institutes of Health (NIH) Consensus
      Development Conference panel unequivocally recommended antimicrobial therapy to
      eradicate Helicobacter pylori in the treatment of peptic ulcer disease. The goal
      of this study was to determine if these recommendations resulted in a change in
      physician prescribing among an underserved population. METHODS: Computerized
      Pennsylvania Medicaid data from January 1993 through February 1996 were used to
      evaluate prescribing patterns in the year before and 2 years after the NIH
      conference. An interrupted time series model, based on 12,737 outpatient peptic
      ulcer disease encounters, assessed the impact of the conference in influencing
      physician prescribing. RESULTS: The prescription of antimicrobial agents for the
      treatment of peptic ulcer disease significantly increased across the study
      period, from 6.5% in January 1993 to 10.2% in February 1996. Similarly, the
      prescription rate for the proton pump inhibitor, omeprazole, significantly
      increased from 9.4% in January 1993 to 25.6% in February 1996. Neither trend,
      however, could be attributed to the NIH Consensus Development Conference.
      Stratification by physician specialty, ulcer type, nonsteroidal anti-inflammatory
      drug use, and patient demographics did not affect these results. The traditional
      treatment approach, using H2-receptor antagonists, remained the preferred
      pharmacotherapy (72% of all prescriptions). CONCLUSIONS: Two years after the
      highly publicized NIH conference on the eradication of Helicobacter pylori,
      antimicrobial agents were not widely prescribed among the Pennsylvania Medicaid
      population. In treating this underserved population, physicians do not appear to
      be using recommendations developed by an NIH expert panel based on recent
      scientific advances.

PMID- 9596057
TI  - Revision rates after knee replacement in the United States.
AB  - OBJECTIVES: Each year approximately 100,000 Medicare patients undergo knee
      replacement surgery. Patients, referring physicians, and surgeons must consider a
      variety of factors when deciding if knee replacement is indicated. One factor in
      this decision process is the likelihood of revision knee replacement after the
      initial surgery. This study determined the chance that a revision knee
      replacement will occur and which factors were associated with revision. METHODS:
      Data on all primary and revision knee replacements that were performed on
      Medicare patients during the years 1985 through 1990 were obtained. The
      probability that a revision knee replacement occurred was modeled from data for
      all patients for whom 2 full years of follow-up data were available. Two
      strategies for linking revisions to a particular primary knee replacement for
      each patient were developed. Predictive models were developed for each linking
      strategy. ICD-9-CM codes were used to determine hospitalizations for primary knee
      replacement and revision knee replacement. RESULTS: More than 200,000
      hospitalizations for primary knee replacements were performed, with fewer than 3%
      of them requiring revision within 2 years. The following factors increase the
      chance of revision within 2 years of primary knee replacement: (1) male gender,
      (2) younger age, (3) longer length of hospital stay for the primary knee
      replacement, (4) more diagnoses at the primary knee replacement hospitalization,
      (5) unspecified arthritis type, (6) surgical complications during the primary
      knee replacement hospitalization, and (7) primary knee replacement performed at
      an urban hospital. CONCLUSIONS: Revision knee replacement is uncommon.
      Demographic, clinical, and process factors were related to the probability of
      revision knee replacement.

PMID- 9596058
TI  - Cost-effectiveness of a hospital-based smoking cessation intervention.
AB  - OBJECTIVES: This study evaluated the cost-effectiveness of a smoking cessation
      and relapse-prevention program for hospitalized adult smokers from the
      perspective of an implementing hospital. It is an economic analysis of a two
      group, controlled clinical trial in two acute care hospitals owned by a large
      group-model health maintenance organization. The intervention included a 20
      minute bedside counseling session with an experienced health counselor, a 12
      minute video, self-help materials, and one or two follow-up calls. METHODS:
      Outcome measures were incremental cost (above usual care) per quit attributable
      to the intervention and incremental cost per discounted life-year saved
      attributable to the intervention. RESULTS: Cost of the research intervention was
      $159 per smoker, and incremental cost per incremental quit was $3,697.
      Incremental cost per incremental discounted life-year saved ranged between $1,691
      and $7,444, much less than most other routine medical procedures. Replication
      scenarios suggest that, with realistic implementation assumptions, total
      intervention costs would decline significantly and incremental cost per
      incremental discounted life-year saved would be reduced by more than 90%, to
      approximately $380. CONCLUSIONS: Providing brief smoking cessation advice to
      hospitalized smokers is relatively inexpensive, cost-effective, and should become
      a part of the standard of inpatient care.

PMID- 9596059
TI  - Health care characteristics associated with women's satisfaction with prenatal
      care.
AB  - OBJECTIVES: The objective of this study was to explore the relation between
      prenatal care characteristics and satisfaction among Medicaid recipients.
      METHODS: African-American (n = 75) and Mexican-American (n = 26) nonadolescent
      primiparous pregnant women who had at least three prenatal care visits
      participated in a 25-minute telephone survey that asked them about satisfaction
      with prenatal care (art of care, technical quality, physical environment, access,
      availability and efficacy); prenatal care characteristics (practitioner
      attributes, service availability, and features of the delivery of care); and,
      personal characteristics (sociodemographics, health status and behaviors, and
      pregnancy-related variables). Univariate and multivariable analyses were
      conducted to explore the relations between personal characteristics and
      satisfaction and between care characteristics and satisfaction. RESULTS: For the
      overall sample, the following prenatal care characteristics were associated with
      increased satisfaction: having procedures explained by the provider, short
      waiting times at the prenatal care site, the availability of ancillary services,
      and reporting that the prenatal care practitioner was male. When examining the
      data by ethnicity, whether the provider explained procedures was the most
      important determinant of satisfaction for both African-American and Mexican
      American women. CONCLUSIONS: Knowledge of the care characteristics that impact
      low-income pregnant women's satisfaction can be utilized to alter service
      delivery to increase use of prenatal care and ultimately to improve perinatal
      outcomes.

PMID- 9596060
TI  - Application of functional independence measure-function related groups and
      resource utilization groups-version III systems across post acute settings.
AB  - OBJECTIVES: The present study evaluated alternative patient classification
      systems for skilled nursing facility and rehabilitation facility patients.
      METHODS: Medicare patients were selected from a random sample of 27
      rehabilitation facilities and 65 skilled nursing facilities participating in a
      national longitudinal study of subacute care. Detailed casemix and resource use
      data was obtained on 513 patients with hip fracture and 483 stroke patients. The
      Functional Independence Measure-Function Related Groups (FIM-FRGs) classification
      system for rehabilitation facilities was replicated on length of stay and tested
      on resource use for rehabilitation facility patients as well as for skilled
      nursing facility patients. Modifications to the FIM-FRGs also were tested. The
      Resource Utilization Groups-Version III classification was tested on
      rehabilitation facility patients. RESULTS: The FIM-FRGs explained the same amount
      of variance in length of stay as in the original FIM-FRGs development sample (R2
      hip fracture = 0.14, R2 stroke = 0.28), and similar variance in resource use. A
      modified version of the FIM-FRGs explained more variance in length of stay (R2
      hip fracture = 0.19, R2 stroke = 0.39) and resource use (R2 hip fracture = 0.20,
      R2 stroke = 0.41). Neither model adequately predicted length of stay or resource
      use in skilled nursing facility patients. The Resource Utilization Groups-Version
      III rehabilitation groups accounted for little variance in rehabilitation
      facility patients' per-diem resource use (R2 = 0.11). CONCLUSIONS: The FIM-FRGs
      are valid for resource use as well as length of stay for rehabilitation facility
      patients, but are not valid for skilled nursing facility patients. Similarly, the
      Resource Utilization Groups-Version III system does not apply to rehabilitation
      facility patients. Related work, however, suggests that development of a single
      episode-based patient classification system for skilled nursing facility and
      rehabilitation facility patients is possible and should be pursued.

PMID- 9596061
TI  - The incentive effects of malpractice liability rules on dental practice behavior.
AB  - OBJECTIVES: The impact of malpractice liability rules on dental practice behavior
      was estimated using data from a 1992 nationwide survey of US general dentists.
      The study examined the premise that malpractice liability rules can affect
      quality of care and related resource allocation decisions by dentists, but that
      market features, such as relatively complete and "non-experience rated"
      malpractice insurance, are likely to weaken the incentive effects of malpractice
      liability. METHODS: General practice dentists in the United States were selected
      randomly, and 3,048 dentists were studied by mail survey. Secondary data on
      county-level characteristics were used to measure market area factors. Quality-of
      care measures were derived from the survey about self-reported practice policies
      and behavior and participation in continuing education. Legal measures were
      assembled from state statutes and appellate court decisions. Ordinary least
      squares was used to assess the relation between legal variables and dependent
      variables of quality of care, continuing education, and the rate of dental
      output. RESULTS: Hypotheses about the effects of malpractice law on practice
      quality and participation in continuing education were not supported. The
      relation between pro-dentist law and output was supported. A number of legal
      provisions related to differences in practice behavior, but often in ways
      opposite to the expected direction. CONCLUSIONS: The direct effects of specific
      malpractice liability rules on dentist practice behavior often failed to point in
      the direction predicted by theory and were economically insignificant. It is
      possible that relatively complete malpractice liability insurance, coupled with
      "noisy" liability rules, substantially dulls the deterrent effect of malpractice
      liability. Other forces, such as the dentist's past malpractice claims
      experience, were more significant in shaping dentist behavior.

PMID- 9596062
TI  - The influence of psychiatric disorders on patients' ratings of satisfaction with
      health care.
AB  - OBJECTIVES: Patient ratings of satisfaction with health care have been used by
      patients, insurers, and employers seeking data to compare the quality of health
      plans and systems of care. Concerns with these ratings include their subjective
      nature and potential for being influenced by patient characteristics unrelated to
      the quality of their care. The authors examined the influence of an active
      psychiatric disorder on patient satisfaction with health care, hypothesizing that
      patients with psychiatric disorders would be less satisfied with their health
      care, due to the adverse effects of these conditions on mood and cognition.
      METHODS: The authors used linked claims and survey data from the 1991 Medicare
      Current Beneficiary Survey. Using logistic regressions that controlled for
      patient sociodemographic and clinical characteristics, the authors examined the
      influence of an active psychiatric disorder on satisfaction with overall quality
      of health care and with specific dimensions of quality. The authors also examined
      the effects of specific types of psychiatric disorders. RESULTS: Aged and
      disabled beneficiaries with psychiatric disorders were significantly less likely
      than those without disorders to be satisfied with the overall quality of health
      care, follow-up care, and the physician's concern for their overall health.
      Disabled beneficiaries were also less likely to be satisfied with the health
      information provided. Further variation was found by type of psychiatric
      disorder. CONCLUSIONS: One interpretation of these findings is that Medicare
      beneficiaries with psychiatric disorders receive lower quality care, a
      possibility that warrants further investigation. Alternatively, patients with
      psychiatric disorders may report lower satisfaction despite receiving comparable
      health care; this interpretation points toward the need for casemix adjustment
      when comparing satisfaction ratings across health plans and the development of
      quality measures less susceptible to subjective biases.

PMID- 9596063
TI  - The Primary Care Assessment Survey: tests of data quality and measurement
      performance.
AB  - OBJECTIVES: The authors examine the data quality and measurement performance of
      the Primary Care Assessment Survey (PCAS), a patient-completed questionnaire that
      operationalizes formal definitions of primary care, including the definition
      recently proposed by the Institute of Medicine Committee on the Future of Primary
      Care. METHODS: The PCAS measures seven domains of care through 11 summary scales:
      accessibility (organizational, financial), continuity (longitudinal, visit
      based), comprehensiveness (contextual knowledge of patient, preventive
      counseling), integration, clinical interaction (clinician-patient communication,
      thoroughness of physical examinations), interpersonal treatment, and trust. Data
      from a study of Massachusetts state employees (n = 6094) were used to evaluate
      key measurement properties of the 11 PCAS scales. Analyses were performed on the
      combined population and for each of the 16 subgroups defined according to
      sociodemographic and health characteristics. RESULTS: The 11 PCAS scales
      demonstrated consistently strong measurement characteristics across all subgroups
      of this adult population. Tests of scaling assumptions for summated rating scales
      were well satisfied by all Likert-scaled measures. Assessment of data
      completeness, scale score dispersion characteristics, and inter-scale
      correlations provide strong evidence for the soundness of all scales, and for the
      value of separately measuring and interpreting these concepts. CONCLUSIONS: With
      public and private sector policies increasingly emphasizing the importance of
      primary care, the need for tools to evaluate and improve primary care performance
      is clear. The PCAS has excellent measurement properties, and performs
      consistently well across varied segments of the adult population. Widespread
      application of an assessment methodology, such as the PCAS, will afford an
      empiric basis through which to measure, monitor, and continuously improve primary
      care.

PMID- 9596064
TI  - A classification tree analysis of selection for discretionary treatment.
AB  - OBJECTIVES: To study treatment bias in observational outcomes research, the
      authors present a nonlinear classification tree model of clinical and
      psychosocial factors influencing selection for interventional management (lower
      extremity bypass surgery or angioplasty) for patients with intermittent
      claudication. METHODS: The study sample includes 532 patients with mild to
      moderate lower extremity vascular disease, without prior peripheral
      revascularization procedures or symptoms of disease progression. All patients
      were enrolled in a prospective outcomes study at the time of an initial referral
      visit for claudication to one of the 16 Chicago-area vascular surgery offices or
      clinics in 1993-95. The influence of baseline sociodemographic, clinical, and
      patient self-reported health status data on subsequent treatment is analyzed.
      Study variables were derived from lower extremity blood flow records and patient
      questionnaires. Follow-up home health visits were used to ascertain the frequency
      of lower extremity revascularization procedures within 6 months of study
      enrollment. Hierarchically optimal classification tree analysis (CTA) was used to
      obtain a nonlinear model of treatment selection. The model retains attributes
      with the highest sensitivity at each node based on cutpoints that maximize
      classification accuracy. Experimentwise Type I error is ensured at P < 0.05 by
      the Bonferroni method and jackknife validity analysis is used to assess model
      stability. RESULTS: Seventy-one of 532 patients (13.3%) underwent interventional
      procedures within 6 months. Ten patient attributes were used in the CTA model,
      which had an overall classification accuracy of 89.5% (67.6% sensitive and 92.9%
      specific), achieving 57.7% of the theoretical possible improvement in
      classification accuracy beyond chance. Eleven model prediction endpoints
      reflected a 33-fold difference in odds of undergoing lower extremity
      revascularization. CONCLUSIONS: Initial ankle-brachial index (100%), leg symptom
      status over the previous six months (89%), self-reported community walking
      distance (74%) and prior willingness to undergo a lower extremity hospital
      procedure (39%) were used to classify most patients in the sample. These
      attributes are critical control variables for a valid observational study of
      treatment effectiveness.

PMID- 9596065
TI  - Assessment of the validity and reliability of three systems of medical record
      screening for quality of care assessment.
AB  - OBJECTIVES: The authors compared the validity and reliability of three methods of
      medical record screening for detecting problems with quality of care of patients
      undergoing cardiovascular procedures: (1) the Uniform Clinical Data Set System
      (UCDSS), a software-based system developed by the Health Care Financing
      Administration (HCFA), (2) the HCFA generic screens, and (3) the Harvard Medical
      Practice Study (HMPS) screening criteria. METHODS: A random sample of 451 medical
      records of inpatients who underwent cardiovascular procedures were screened by
      trained nurses and were also examined by physicians masked to screening results.
      Physicians' judgment provided a reference standard for validity assessment of
      screening applied by nurses. RESULTS: Agreement between pairs of physician
      reviews about the quality of care was fair or slight (Kappa < 0.40). Agreement
      between nurses about presence of any screening flags was excellent for UCDSS
      (0.93), slight for HCFA (0.11), and fair for HMPS (0.41). The UCDSS was more
      sensitive to quality problems agreed on by two physicians than HCFA or HMPS (85%,
      74%, and 69%, respectively), but was also less specific (48%, 57%, and 56%,
      respectively). The UCDSS was much more labor-intensive with an average of 6.7
      hours of nurse review per quality problem disclosed versus 2 hours required by
      HCFA and HMPS. CONCLUSIONS: The UCDSS computerized screens brought about
      substantial improvements in reliability of medical record screening, but needed
      to reduce its false-positive rate and to increase efficiency before it is used.
      From the perspective of continuous quality improvement, the UCDSS computerized
      algorithms provided a starting point to developing disease-specific patterns of
      practice to guide interventions.

PMID- 9596066
TI  - The MOS 36-Item Short Form Health Survey: reliability, validity, and preliminary
      findings in schizophrenic outpatients.
AB  - OBJECTIVES: The authors test the reliability and validity of the Medical Outcomes
      Study Short Form 36-Item Health Survey (SF-36) as a written, self-administered
      survey in outpatients with chronic schizophrenia. METHODS: Thirty-six
      schizophrenic outpatients completed a written and oral form of the SF-36. A
      psychiatrist rated the patients using the Brief Psychiatric Rating Scale to
      determine severity of psychopathology. Cognitive functioning and academic
      achievement were also assessed. Internal consistency, test-retest reliability,
      concurrent and discriminative validity of the oral and written versions were
      determined. RESULTS: The SF-36 in both forms was shown to have good internal
      consistency, stability, and concurrent validity. The mental health SF-36
      subscales had poor discriminant validity, compared with the physical functioning
      scale that demonstrated good discriminant validity. CONCLUSIONS: The validity of
      using the written form of the SF-36 on a sample of patients with chronic mental
      illness was demonstrated. The SF-36 appears to be an appropriate outcome measure
      for changes in physical and role functioning in consumers of outpatient mental
      health programs.

PMID- 9596067
TI  - The Home Infusion Therapy/Relative Benefit Index: summary of an analysis using
      insurance claims data.
AB  - OBJECTIVES: The cost of providing services is the traditional criteria used by
      payers in making selective contracting decisions regarding home care providers in
      general, and home infusion therapy (HIT) vendors specifically for this analysis.
      This approach assumes comparable health outcomes, for which adequate measures
      often are unavailable. In practice, poor quality can result in a need for
      remedial services. The objective of this research is to develop a method to use
      health insurance claims data to incorporate the hidden costs of adverse outcomes
      into an analysis of the costs of a vendor's HIT. METHODS: The Home Infusion
      Therapy/Relative Benefit Index (HIT/RBI) model incorporates measures of both the
      cost of providing HIT services as well as the cost of remedial treatment for the
      adverse outcomes that may result from HIT care, eg, emergency room visits. The
      data source for the analysis is the health care claims for a sample of managed
      care patients of national insurer for the period 1990 to 1994. RESULTS: The
      analysis confirms that adverse clinical outcomes can lead to additional demand
      for remedial health care with resultant negative financial consequences. When the
      cost of the adverse outcomes is incorporated into the analysis, vendors who
      appeared to be low cost on the basis of HIT services, in fact were higher cost
      vendors, whereas vendors with a high cost of services but with few adverse events
      were low cost vendors. CONCLUSIONS: Payers should consider both the clinical and
      economic consequences of providing care into account in selecting vendors. The
      HIT/RBI model is a useful tool for incorporating the cost of adverse outcomes
      into a comprehensive comparison of the cost multiple vendors of HIT services.

PMID- 9596068
TI  - Discriminant and criterion validation of the US-Spanish version of the SF-36
      Health Survey in a Cuban-American population with benign prostatic hyperplasia.
AB  - OBJECTIVES: The study tested the validity of the Medical Outcomes Study 36-Item
      Short-Form (SF-36) Health Survey (originally validated in the Mexican-American
      population) in a different Spanish subgroup to determine whether the Spanish
      version is equally applicable to the Cuban-American population. METHODS:
      Individuals with and without benign prostatic hyperplasia served as the study
      sample. The SF-36 scores of 264 individuals with benign prostatic hyperplasia
      were compared with those of 273 individuals without benign prostatic hyperplasia
      to determine discriminant and criterion validity. These individuals were assigned
      to one of the following groups: non-Hispanic subjects, Cuban subjects who took
      the English version, and Cuban subjects who took the Spanish version. MANOVA with
      planned comparisons was used for this analysis. RESULTS: In all three
      culture/language groups, the quality-of-life scores of individuals without benign
      prostatic hyperplasia were significantly different than those of benign prostatic
      hyperplasia individuals. These results demonstrated that the English and Spanish
      versions can differentiate between individuals with and without benign prostatic
      hyperplasia. Moreover, the quality-of-life scores of Cuban subjects with and
      without benign prostatic hyperplasia who took the English version were
      statistically similar to those of their counterparts who took the Spanish
      version. CONCLUSIONS: The US-Spanish version of the SF-36 appears to be valid
      when used to measure health status in Cuban-American subjects with benign
      prostatic hyperplasia. Further studies should be conducted to verify the validity
      of the US-Spanish version of the SF-36 for other health conditions.

PMID- 9596069
TI  - Long-term regulation of renal urea transporter protein expression in rat.
AB  - To test the hypothesis that the abundance of the apical urea transporter of the
      inner medullary collecting duct (IMCD) is regulated in vivo by factors associated
      with altered water balance, immunoblots of rat inner medullary membrane fractions
      were probed with rabbit polyclonal antibodies against the renal urea transporter
      (RUT) gene product. In inner medullas of Brattleboro rats, which manifest severe
      chronic water diuresis, a 117-kD band was seen, in addition to the previously
      described 97-kD band. These two bands were detectable by antibodies directed
      against two different regions of the RUT sequence. When Brattleboro rats were
      treated with a 5-d infusion of arginine vasopressin (AVP) by osmotic minipump,
      the 117-kD band was markedly diminished, whereas the 97-kD band was unchanged.
      Simultaneous infusion of the diuretic agent furosemide prevented the AVP-induced
      decrease in the 117-kD band. In AVP-infused Sprague Dawley rats, the 117-kD band
      was barely perceptible. However, when AVP-treated rats were infused with
      furosemide for 5 d, the 117-kD band was markedly accentuated, whereas the 97-kD
      band was unchanged. The abundance of the 117-kD RUT protein in the renal papilla
      was inversely correlated with dietary protein intake. Further immunoblotting
      studies revealed that the 117-kD protein is heavily expressed in IMCD cells and
      not in non-collecting duct components of the inner medulla, and is present in low
      density microsome fractions from inner medulla. From this study, the following
      conclusions can be made: (1) The collecting duct urea transporter is present in
      at least two forms (97 and 117 kD) in the IMCD. (2) The expression level of the
      117-kD urea transporter protein is regulated and is inversely correlated with
      medullary osmolality and urea concentration, but does not correlate with
      circulating AVP level. (3) Although AVP regulates RUT function on a short-term
      basis, long-term changes in AVP levels do not increase RUT abundance.

PMID- 9596070
TI  - Long-term regulation of inner medullary collecting duct urea transport in rat.
AB  - Facilitated urea transport is regulated acutely by arginine vasopressin (AVP) and
      hyperosmolality in rat terminal inner medullary collecting duct (IMCD). This
      study tested whether chronic diuresis or antidiuresis regulates facilitated urea
      transport. Basal and AVP-stimulated urea permeabilities (Purea) were measured in
      perfused IMCD subsegments. Rats were made: (1) diuretic by giving them sugar
      water (with or without food) or furosemide; or (2) antidiuretic by water
      deprivation. They were then compared with untreated rats given food and water ad
      libitum. Terminal IMCD from untreated rats had a high basal Purea that was
      significantly increased by AVP. Diuresis significantly increased basal Purea in
      terminal IMCD in all five diuresis protocols. Water deprivation for 1 or 3 d had
      no effect on basal or AVP-stimulated Purea in the IMCD2 subsegment of the
      terminal IMCD. In contrast, 3 d of water deprivation significantly increased both
      basal and AVP-stimulated Purea in the IMCD3 subsegment; 1 d of water deprivation
      had no effect on basal or AVP-stimulated Purea. Next, initial IMCD (IMCD1) were
      studied. Initial IMCD from untreated rats had a low basal Purea that was not
      increased by AVP (10 nM). Water diuresis (with or without food) for 3 to 5 d had
      no effect on basal Purea but significantly increased AVP-stimulated Purea.
      Furosemide diuresis and water diuresis for 1 or 7 d had no effect on either basal
      or AVP-stimulated Purea in initial IMCD. Water deprivation for 2 to 3 d, but not
      for 1 d, significantly increased basal Purea in initial IMCD, whereas water
      deprivation for 1 d increased AVP-stimulated Purea. It is concluded that chronic
      changes in hydration cause heterogeneous changes in facilitated urea transport in
      rat IMCD subsegments.

PMID- 9596071
TI  - Characterization of anion exchangers in an inner medullary collecting duct cell
      line.
AB  - Although the inner medullary collecting duct (IMCD) plays a major role in urinary
      acidification, the molecular identification of many of the specific components of
      the transport system in this nephron segment are lacking. A cultured line of rat
      IMCD cells was used to characterize the mediators of cellular HCO3 exit. This
      cell line functionally resembles alpha-intercalated cells. Physiologic
      experiments document that HCO3- transport is a reversible, electroneutral, Cl
      dependent, Na+-independent process. It can be driven by Cl-gradients and
      inhibited by stilbenes such as 4-acetamido-4'-isothiocyanatostilbene-2,2'
      disulfonic acid. Immunohistochemical analysis, using a rabbit polyclonal antibody
      against the carboxy-terminal 12 amino acids of anion exchanger 1 (AE1), revealed
      a distribution of immunoreactive protein that is consistent with a basolateral
      localization of AE in cultured cells and in alpha-intercalated cells identified
      in sections of rat kidney cortex. Immunoblot revealed two immunoreactive bands
      (approximately 100 and 180 kD in size) in membranes from cultured IMCD cells, rat
      renal medulla, and freshly isolated IMCD cells. The mobility of the lower
      molecular weight band was similar to that of AE1 in red blood cell ghosts and
      kidney homogenate and therefore probably represents AE1. The mobility of the 180
      kD band is similar to that for rat stomach and kidney AE2 and therefore probably
      represents AE2. Selective biotinylation of the apical or basolateral membrane
      proteins in cultured IMCD cells revealed that both AE1 and AE2 are polarized to
      the basolateral membrane. Northern blot analysis documented the expression of
      mRNA for AE1 and AE2 but not AE3. Furthermore, the cDNA sequence of AE1 and AE2
      expressed by these cells was found to be virtually identical to that reported for
      kidney AE1 and rat stomach AE2. It is concluded that this cultured line of rat
      IMCD cells expresses two members of the anion exchanger gene family, AE1 and AE2,
      and both of these exchangers probably mediate the electroneutral Cl--dependent
      HCO3-transport observed in this cell line.

PMID- 9596072
TI  - Endothelin A receptor blockade alleviates hypertension and renal lesions
      associated with chronic nitric oxide synthase inhibition.
AB  - Unopposed actions of vasoconstrictors, such as angiotensin, play an important
      role in the effects of chronic nitric oxide synthase (NOS) inhibition. In this
      study, it is hypothesized that endothelin (ET), another important
      vasoconstrictor, may also play a role in the development of hypertension and
      renal lesions during chronic NOS inhibition. The ET(A) receptor was blocked with
      A-127722 during chronic NOS inhibition with Nomega-nitro-L-arginine (L-NNA), a
      potent NOS inhibitor without antimuscarinic action. Male Sprague Dawley rats were
      treated for 3 wk with L-NNA (40 mg/kg per d), L-NNA (40 mg/kg per d) + A-127722
      (30 mg/kg per d), or remained untreated (control). In preliminary experiments, L
      NNA (40 mg/kg per d) had been found to cause the maximum increase of systolic BP
      and a 35% decrease in renal NOS activity. Three weeks of L-NNA treatment resulted
      in a marked rise in systolic BP (240+/-4 versus control 151+/-7 mmHg; P < 0.01),
      proteinuria (209+/-46 versus control 27+/-3 mg/d; P < 0.01), and a fall in GFR
      (1.41+/-0.16 versus control 2.23+/-0.19 ml/min; P < 0.05). Renal morphology
      showed severe vascular injury, characterized by focal adhesion and infiltration
      of mononuclear cells into the intima and media of preglomerular arteries and
      arterioles. This was sometimes associated with necrosis of the media and partial
      or total obstruction of the lumen with thrombotic material. Ischemic glomeruli
      were also present. Tubulointerstitial damage was moderate and accompanied by an
      influx of monocytes and macrophages. A-127722 administered simultaneously with L
      NNA completely prevented the increase in proteinuria (39+/-8 mg/d) and glomerular
      ischemia. Vascular injury, tubulointerstitial damage, and the increase in
      systolic BP (191+/-6 mmHg) were partially prevented. The protective effects of
      ET(A) receptor blockade suggest that ET has hemodynamic as well as nonhemodynamic
      effects in the cascade of events following chronic NOS inhibition.

PMID- 9596073
TI  - Regulation of glomerular TGF-beta expression in the contralateral kidney of two
      kidney, one-clip hypertensive rats.
AB  - Previous studies have demonstrated that angiotensin II stimulates expression of
      transforming growth factor-beta (TGF-beta) in cultured renal cells. To
      investigate whether similar mechanisms are operative in vivo, glomerular TGF-beta
      mRNA expression was investigated in two-kidney, one-clip (2-K 1-C) hypertensive
      rats. Glomerular TGF-beta1 transcripts were elevated in the clipped kidney 6 d,
      but not 3 d, after surgery. Later, during the course of the disease (21 to 35 d),
      TGF-beta1 mRNA was upregulated in contralateral kidneys compared with sham
      operated control kidneys. There was no difference in plasma TGF-beta1 levels
      between 2-K 1-C rats and controls. Treatment with the AT1 receptor antagonist
      losartan, as well as with triple therapy (hydralazine, reserpine, and
      hydrochlorothiazide), started 1 d after clipping, significantly reduced systolic
      BP in hypertensive rats at day 21 after clipping. Both treatments were equally
      effective in preventing the increase in glomerular TGF-beta1 mRNA and protein
      expression in the contralateral kidney at day 21. In a second set of experiments,
      interventional treatment with losartan or triple therapy, starting 14 d after
      surgery, was investigated. This treatment for 3 wk significantly reduced the
      increase in TGF-beta1 expression in the contralateral kidney. At day 35 after
      clipping, considerable glomerular damage and sclerosis were present, mainly in
      contralateral kidneys. Interventional treatment with losartan or triple therapy
      partly prevented this glomerular damage of the contralateral kidney. The data
      demonstrate that TGF-beta1 expression in the contralateral kidney in 2-K 1-C rats
      is regulated by the increase in systemic BP rather than by direct effects of
      angiotensin II.

PMID- 9596074
TI  - Retinoic acid regulation of renal tubular epithelial and vascular smooth muscle
      cell function.
AB  - Vitamin A and its derivatives have been postulated to play an important role in
      renal tubulogenesis and compensatory hypertrophy. This study examined the effects
      of two carboxylic derivatives of vitamin A on Lewis lung carcinoma-porcine kidney
      1 (LLC-PK1) renal tubular epithelial cell mito- and motogenesis and cell size. It
      was found that all-trans and 13-cis retinoic acids exerted modest, dose-dependent
      effects to stimulate incorporation of 3H-thymidine into acid-precipitable
      material of LLC-PK1 cells. The effects of all-trans retinoic acid to promote 3H
      thymidine uptake in LLC-PK1 cells modestly enhanced that seen with acidic
      fibroblastic growth factor. Similar findings of these two retinoic acid
      derivatives to promote 3H-thymidine uptake and to enhance 3H-thymidine uptake
      stimulated by another growth factor (platelet-derived growth factor BB) were also
      observed in cultured bovine aortic smooth muscle cells. Both retinoic acids
      promoted healing of denuded areas made within confluent monolayers of serum
      starved LLC-PK1 cells. All-trans retinoic acid also stimulated recovery of
      mechanically denuded areas within bovine aortic smooth muscle monolayers. Neither
      all-trans nor 13-cis retinoic acids s affected cell size as assessed by forward
      light scatter with flow cytometry, suggesting lack of effect to induce
      hypertrophy. These results demonstrate that two carboxylic acid derivatives of
      vitamin A are capable of stimulation of basal and growth factor-induced
      incorporation of 3H-thymidine uptake into acid-precipitable material and healing
      of denuded areas in disparate cell types. These findings are compatible with a
      role for vitamin A and its analogues in the tissue repair process.

PMID- 9596075
TI  - Age-related increase in expression of TGF-beta1 in the rat kidney: relationship
      to morphologic changes.
AB  - In the kidney, aging is characterized by the development of structural changes,
      including glomerulosclerosis and interstitial fibrosis. Transforming growth
      factor-beta1 (TGF-beta1) is known to play a critical role in the genesis of these
      alterations in pathologic conditions. The present experiments were designed to
      test the hypothesis that TGF-beta1 may be involved in the development of age
      related histopathologic changes in rat kidney, and that captopril, an angiotensin
      converting enzyme inhibitor, may influence the progression of glomerular and
      interstitial lesions. In this study, 3-, 18-, 24-, and 30-mo-old rats were
      examined, and an age-related increase in urinary protein excretion was found;
      plasma creatinine and systolic BP did not change. Significant structural changes,
      including glomerular sclerosis and interstitial fibrosis, were found in the group
      of aged rats (24- and 30-mo-old). Immunostaining for TGF-beta in the renal cortex
      interstitium was increased in the group of 24-mo-old rats, with a parallel
      increase in TGF-beta1 mRNA expression, measured with reverse-transcription PCR.
      Captopril-treated animals showed a statistically significant decrease in urinary
      protein excretion but no significant changes in BP. Moreover, captopril reduced
      the extent of interstitial fibrosis, but did not affect the degree of
      glomerulosclerosis. A significant inhibition of TGF-beta1 mRNA expression was
      observed in the captopril-treated animals. These findings suggest that TGF-beta1
      may act as a fibrogenic growth factor that could be responsible, at least
      partially, for the renal interstitial fibrosis associated with aging. Treatment
      with captopril might delay the progression of these lesions.

PMID- 9596077
TI  - Effect of glycated proteins on the matrix of glomerular epithelial cells.
AB  - In this study, cultured glomerular epithelial cells (GEC) were exposed to a
      diabetic milieu containing glycated proteins to determine whether such proteins
      cause metabolic alterations that may lead to defects seen in the extracellular
      matrix in diabetic nephropathy. Cultured glomerular epithelial cells were cloned
      and maintained in RPMI media containing 10% fetal bovine serum (FBS). The medium
      was changed to RPMI-1% glycated FBS (experimental) or RPMI-1% control FBS, and
      cells were incubated for 1 or 4 d. Mitogenicity was tested by 3H-thymidine
      uptake. The media were collected and analyzed for collagenase activity by a
      quantitative fluorescence assay and by zymography. The cell layers were processed
      for matrix antigen (collagen I, glomerular basement membrane antigens, laminin,
      and fibronectin) and for the proteins of the tight junction (cadherin, desmosomal
      protein) by quantitative immunoperoxidase and immunofluorescence. Cell lysates
      were tested for cadherin and desmosomal protein by immunoblotting. Cells were
      also grown on 0.2-microM filter membranes to test for permeability to 3H-inulin
      and 125I-albumin. Glycated FBS resulted in a 1.8-fold increase in 3H-thymidine
      uptake in subconfluent layers accompanied by an increase in cell number. The
      treatment caused accumulation of laminin (18% above control, P < 0.05) and
      basement membrane antigens (33% above control, P < 0.05). Collagen I and
      fibronectin were unchanged. Exposing cells to glycated FBS changed the
      distribution of cadherin from a linear to a diffuse pattern associated with a
      decrease in cadherin observed on immunoblots. The media of glycated FBS-treated
      cells contained 45% lower collagenase activity (72-, 92-, and 150-kD species).
      Permeability to inulin increased by 550% and to albumin by 320% in glycated FBS
      treated monolayers compared with controls. It is concluded that glycated proteins
      increased the accumulation of matrix proteins in the GEC, associated with a
      concomitant depression in collagenase activity. There were qualitative and
      quantitative changes in the tight junction protein cadherin. These matrix changes
      resulted in a functional defect in the permselective properties of the GEC tight
      junctions and manifested as increased leakage of inulin and albumin. Thus, the
      GEC are metabolically sensitive to the presence of glycated proteins, and this
      could play a role in the pathogenesis of diabetic nephropathy.

PMID- 9596076
TI  - Endogenous fibroblast growth factor-2 mediates cytotoxicity in experimental
      mesangioproliferative glomerulonephritis.
AB  - Fibroblast growth factor-2 (FGF-2) is released from mesangial cells in
      experimental mesangioproliferative glomerulonephritis induced with anti-Thy 1.1
      antibody. To investigate the functional role of released FGF-2, rats received
      either neutralizing anti-FGF-2 IgG or a functional peptide antagonist of FGF-2
      (FGF119-126) before or shortly after induction of anti-Thy 1.1 nephritis. In
      additional experiments, rats were treated with bolus injections of FGF-2 from 2
      to 6 h after disease induction. The data showed that anti-FGF-2 therapy led to
      significant reductions of early mesangial cell injury (mesangiolysis,
      microaneurysm formation) and the subsequent mesangioproliferative changes
      (glomerular de novo expression of alpha-smooth muscle actin, mesangial cell
      proliferation, matrix accumulation, and platelet influx). Conversely, injections
      of FGF-2 augmented both mesangial injury and the subsequent mesangioproliferative
      changes. Studies on the mechanisms underlying the amplification of mesangial cell
      injury by FGF-2 showed that anti-FGF-2 therapy reduced cell death at 2 and 8 h
      after disease induction by 58 and 54%, respectively. This was associated with
      significant reductions in the number of glomerular H2O2- and OH -producing cells,
      as well as reduced glomerular production of nitric oxide. These data suggest that
      release of constitutively expressed FGF-2 after immune-mediated cell injury
      contributes to glomerular cell damage and thus identify FGF-2 as a novel mediator
      of cytotoxicity.

PMID- 9596078
TI  - Mutations in CLCN5 chloride channel in Japanese patients with low molecular
      weight proteinuria.
AB  - Mutations in the CLCN5 gene have been demonstrated in three disorders of
      hypercalciuric nephrolithiasis, i.e., Dent's disease, X-linked recessive
      nephrolithiasis, and X-linked recessive hypophosphatemic rickets. Recently, a
      number of Japanese children with low molecular weight proteinuria (LMWP) showing
      symptoms similar to those shown by patients with Dent's disease in British
      families have also been reported to have mutations in the CLCN5 gene. The present
      study examines five unrelated Japanese families with LMWP, two of which lacked
      any signs other than LMWP, and three of which had several signs other than LMWP,
      i.e., hypercalciuria, aminoaciduria, hypophosphatemia, and rickets. One nonsense
      (E118X) and one missense (W22G) mutation were found in three patients in the two
      families having only LMWP. One genomic deletion including exons 5 to 8 in the
      CLCN5 gene was found in a patient with hypophosphatemic rickets, and a nonsense
      mutation (R347X) was found in one patient with LMWP and slight hypercalciuria. No
      mutations of the exons and exon-intron boundaries in the CLCN5 gene were found in
      one patient with LMWP, aminoaciduria, and hypokalemia. In addition to the
      predicted loss of chloride channel function in these nonsense and deletion
      mutations, the loss of function in the missense mutation W22G was confirmed in
      the Xenopus oocyte expression system. These results clarified four novel
      mutations in the CLCN5 genes, and additionally suggested that the loss-of
      function mutation of the CLCN5 does not necessarily lead to hypercalciuria and
      nephrocalcinosis in the early stage of the disease, and that LMWP is an early and
      essential manifestation of disorders of the CLC-5 chloride channel.

PMID- 9596079
TI  - Peripheral blood mononuclear cells express mutated NCCT mRNA in Gitelman's
      syndrome: evidence for abnormal thiazide-sensitive NaCl cotransport.
AB  - Genetic analysis has demonstrated complete linkage between the human thiazide
      sensitive sodium chloride cotransporter gene (NCCT or TSC) and Gitelman's
      syndrome (GS). Several genomic NCCT mutations have been reported. This study was
      performed to determine whether peripheral blood mononuclear cells (PBMC) express
      NCCT mRNA and whether defective PBMC NaCl cotransport could be demonstrated in
      GS. PBMC were isolated from two brothers with GS, their parents, and healthy
      control subjects. Northern analysis revealed that NCCT mRNA is expressed in PBMC.
      The sequence of full-length NCCT cDNA amplified from normal PBMC was identical to
      human renal NCCT cDNA. Two different mutations were detected in the patients'
      NCCT cDNA (compound heterozygote). In cDNA derived from the patient's maternal
      allele, exon 24 was deleted, resulting in a premature stop codon (after amino
      acid 920). cDNA derived from the patient's paternal allele had an additional 119
      bp insertion between exons 3 and 4, generating a premature stop codon (after
      amino acid 187). The patient's genomic DNA had a previously described 5' splice
      site mutation in intron 24, GGT --> GTT (maternal allele), and a new 3' splice
      site mutation in intron 3, CAG --> CAA (paternal allele), which resulted in the
      activation of a nearby cryptic splice site in intron 3. The latter mutation was
      not present in 300 normal chromosomes. To determine the functional significance
      of these findings, chlorothiazide-inhibitable 22Na uptake was measured in PBMC
      from control subjects, the parents, and the patients with GS in the presence of
      bumetanide. In control PBMC, chlorothiazide inhibited 22Na uptake by
      approximately 9%. PBMC from the two patients with GS failed to respond to
      chlorothiazide. These results demonstrate that PBMC can be used for mutational
      analysis of NCCT mRNA in patients with GS. Furthermore, functional evidence is
      provided that the underlying cause of GS is defective NCCT NaCl cotransport.

PMID- 9596080
TI  - Mechanical strain- and high glucose-induced alterations in mesangial cell
      collagen metabolism: role of TGF-beta.
AB  - Cultured mesangial cells (MC) exposed to cyclic mechanical strain or high glucose
      levels increase their secretion of transforming growth factor-beta1 (TGF-beta1)
      and collagen, suggesting possible mechanisms for the development of diabetic
      renal sclerosis resulting from intraglomerular hypertension and/or hyperglycemia.
      This study examines whether glucose interacts with mechanical strain to influence
      collagen metabolism and whether this change is mediated by TGF-beta. Accordingly,
      rat MC were grown on flexible-bottom plates in 8 or 35 mM glucose media,
      subjected to 2 to 5 d of cyclic stretching, and assayed for TGF-beta1 mRNA, TGF
      beta1 secretion, and the incorporation of 14C-proline into free or protein
      associated hydroxyproline to assess the dynamics of collagen metabolism.
      Stretching or high glucose exposure increased TGF-beta1 secretion twofold and TGF
      beta1 mRNA levels by 30 and 45%, respectively. However, the combination of these
      stimuli increased secretion greater than fivefold without further elevating mRNA.
      In 8 mM glucose medium, stretching significantly increased MC collagen synthesis
      and breakdown, but did not alter accumulation, whereas those stretched in 35 mM
      glucose markedly increased collagen accumulation. TGF-beta neutralization
      significantly reduced baseline collagen synthesis, breakdown, and accumulation in
      low glucose, but had no significant effect on the changes induced by stretch. In
      contrast, the same treatment of MC in high glucose medium greatly reduced stretch
      induced synthesis and breakdown of collagen and totally abolished the increase in
      collagen accumulation. These results indicate that TGF-beta plays a positive
      regulatory role in MC collagen synthesis, breakdown, and accumulation. However,
      in low glucose there is no stretch-induced collagen accumulation, and the effect
      of TGF-beta is limited to basal collagen turnover. In high glucose media, TGF
      beta is a critical mediator of stretch-induced collagen synthesis and catabolism,
      and, most importantly, its net accumulation. These data have important
      implications for the pathogenesis and treatment of diabetic glomerulosclerosis.

PMID- 9596081
TI  - Coronary aneurysms in patients with autosomal dominant polycystic kidney disease.
AB  - Patients with autosomal dominant polycystic kidney disease (ADPKD) have an
      increased risk of intracranial aneurysms. Reports on arterial aneurysms in other
      locations have not been conclusive. The present study was initiated to
      investigate the prevalence of coronary aneurysms. Thirty ADPKD patients who had
      undergone coronary angiography on clinical indication were identified, 15 after
      renal transplantation. For each ADPKD patient, a control patient was identified
      with end-stage renal disease, investigated by coronary angiography, and matched
      for age, sex, and time relation to transplantation. All angiograms were retrieved
      and reevaluated with respect to aneurysms, defined as an increase in artery
      diameter by 50% or more, as well as to pathologic ectasias not fulfilling this
      criterion. Aneurysms were detected in four ADPKD patients and two control
      subjects. Five more ADPKD patients, but none of the control subjects, had minor
      ectasias. One ADPKD patient had a dissecting aortic aneurysm, and another died of
      aortic dissection during bypass surgery. This study adds to the evidence of an
      increased risk of extracranial aneurysms in ADPKD patients.

PMID- 9596082
TI  - Relapse rate, renal survival, and cancer morbidity in patients with Wegener's
      granulomatosis or microscopic polyangiitis with renal involvement.
AB  - Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are both
      frequently associated with antineutrophil cytoplasmic autoantibodies (ANCA).
      Immunosuppressive treatment has dramatically improved outcome for these patients,
      but today we have to deal with the problems of relapses, cases refractory to
      treatment, and long-term side effects of therapy. This study comprises a
      consecutive series of 123 patients with WG (n=56) or MPA (n=67) with biopsy
      confirmed renal involvement, followed up for a median of 55 mo (range, 0.1 to
      273.2 mo). ANCA was detected by enzyme-linked immunosorbent assay in 97% of
      patients. Nearly half of the patients (46%) relapsed. There was no statistically
      significant difference in overall relapse rate according to type of ANCA. Renal
      survival was 78% in patients alive at the end of follow-up. Three variables
      seemed important for renal survival: serum creatinine, the titer of proteinase 3
      ANCA measured by capture enzyme-linked immunosorbent assay, and B thrombocyte
      count, at time of referral. Cancer incidence data were obtained from the
      population-based South Swedish Regional Tumor Registry. Standardized morbidity
      ratio was calculated using expected values from the health care region. We found
      an 11-fold increase in risk for bladder cancer in patients treated with
      cyclophosphamide for at least 12 mo. Skin carcinoma had the strongest
      relationship with azathioprine use for at least 12 mo and with corticosteroid
      therapy for at least 48 mo. In addition, four patients developed myelodysplastic
      syndrome and five had carcinoma in situ of the skin. Because the therapeutic
      regimen used today is not efficient enough to prevent relapses and is associated
      with a host of side effects, of which the risk for cancer is by far the most
      important, improved therapy and medical care are needed for patients with WG and
      MPA.

PMID- 9596083
TI  - Epidemiology of IgA nephropathy in central and eastern Kentucky for the period
      1975 through 1994. Central Kentucky Region of the Southeastern United States IgA
      Nephropathy DATABANK Project.
AB  - Population-based incidence data for IgA nephropathy (IgAN) are available for some
      countries but not for the United States. The purpose of this study was to
      determine the incidence of IgAN in central and eastern Kentucky for 5- and 10-yr
      periods between 1975 and 1994 and to examine differences among patient groups
      between those periods. The incidence of IgAN was 5.4 cases per one million
      population per year (MPPY) for period 1A (1975 through 1979), increasing to 12.4
      cases per MPPY for period 2B (1990 through 1994) (P < 0.001). Males had a 2.7
      times higher incidence than females for period 1 (1975 through 1984) and 2.2
      times higher for period 2 (1985 through 1994). For period 1A, the incidence for
      Fayette County, which includes the city of Lexington, was lower than that of the
      rest of the study area (P=0.26), whereas for period 2 the incidence was higher
      for Fayette County (P=0.052). During period 1, the highest incidence of IgAN for
      any age and gender group was 24.3 cases per MPPY for males ages 30 through 39.
      For period 2, the incidence for males was similar for each decade between ages 20
      and 59 (approximately 19 cases per MPPY). No African-American was diagnosed
      during period 1, but in period 2 incidences for blacks and whites were similar
      (10.7 and 10.2 cases per MPPY, respectively). For the last 5 yr of the study
      (1990 through 1994), the incidence of end-stage renal disease (ESRD) due to IgAN
      was 5.5 cases per MPPY: 8.4 for males and 2.7 for females. The incidence of IgAN
      in Kentucky for period 2B was still much lower than that in European studies, but
      the incidence of ESRD due to IgAN may be similar. Thus, IgAN may be as important
      a condition with respect to ESRD in Kentucky as it is in other regions of the
      world.

PMID- 9596084
TI  - Nocturnal hemodialysis: three-year experience.
AB  - There is evidence that high frequency, as well as long duration, hemodialysis
      provides better clinical outcomes. We developed nocturnal hemodialysis, a new
      innovative form of renal replacement therapy, which is performed six to seven
      nights per week for 8 to 10 h during sleep at home. Blood flow was set at 300
      ml/min and dialysate flow at 100 ml/min. An internal jugular catheter was used as
      the vascular access. Special precautions were taken to prevent accidental
      disconnection during sleep, as well as air embolization. Dialysis functions from
      the patient's home were monitored continuously via a modem at the nocturnal
      hemodialysis center. Twelve patients have completed training and have been
      successfully performing nocturnal hemodialysis for up to 34 mo. This study
      represents 170 patient months of experience accumulated over 3 yr. There was
      hemodynamic stability and significant subjective improvement in patient well
      being. Nightly Kt/V was 0.99. Weekly removal of phosphate was twice as high and
      beta2 microglobulin 4 times as high as conventional hemodialysis. All patients
      have discontinued their phosphate binders and have increased dietary phosphate
      and protein intake. BP control was achieved with fewer medications. Dialyzer
      reuse has decreased the operating costs to the level of the other form of home
      dialysis. Complications were infrequent and were related primarily to the
      dialysis access. Nocturnal hemodialysis represents the most efficient form of
      dialysis at low cost and should be considered as an option for patients who can
      be trained for home hemodialysis.

PMID- 9596085
TI  - EPIBACDIAL: a multicenter prospective study of risk factors for bacteremia in
      chronic hemodialysis patients.
AB  - Bacteremic infections are a major cause of mortality and morbidity in chronic
      hemodialysis patients. New developments in managing these patients
      (erythropoietin therapy, nasal mupirocin, long-term implanted catheters, and
      synthetic membranes) may have altered the epidemiologic patterns of bacteremia in
      dialysis patients. This multicenter prospective cross-sectional study was carried
      out to determine the current incidence of and risk factors for bacteremia in
      chronic hemodialysis patients in France. A total of 988 adults on chronic
      hemodialysis for 1 mo or longer was followed up prospectively for 6 mo in 19
      French dialysis units. The factors associated with the development of at least
      one bacteremic episode over 6 mo were determined using the multivariate Cox
      proportional hazards model. Staphylococcus aureus (n=20) and coagulase-negative
      staphylococci (n=15) were responsible for most of the 51 bacteremic episodes
      recorded. The incidence of bacteremia was 0.93 episode per 100 patient-months.
      Four risk factors for bacteremia were identified: (1) vascular access (catheter
      versus fistula: RR=7.6; 95% CI, 3.7 to 15.6); (2) history of bacteremia (> or =2
      versus no previous episode: RR=7.3; 95% CI, 3.2 to 16.4); (3) immunosuppressive
      therapy (current versus no: RR=3.0; 95% CI, 1.0 to 6.1); and (4) corpuscular
      hemoglobin (per 1 g/dl increment: RR=0.7; 95% CI, 0.6 to 0.9). Catheters,
      especially long-term implanted catheters, were found to be the leading risk
      factor of bacteremia in chronic hemodialysis patients. There was a trend toward
      recurrence of bacteremia that was not associated with chronic staphylococcal
      nasal carriage. Synthetic membranes were not associated with a lower risk of
      bacteremia in this population of well dialyzed patients, but anemia linked to
      resistance to erythropoietin appeared to be a possible risk factor for
      bacteremia.

PMID- 9596086
TI  - Effects of controlled blood cooling on hemodynamic stability and urea kinetics
      during high-efficiency hemodialysis.
AB  - Although the use of cooled dialysate during hemodialysis is associated with
      stabilization of intradialytic BP, the effects of blood cooling on hemodynamics
      and urea kinetics in high-efficiency hemodialysis have not been completely
      studied. In particular, the effects of blood cooling have not been elucidated in
      very short-time, high K/V dialysis treatments, in which postdialysis urea rebound
      is maximized. In theory, blood cooling could increase urea compartmentalization
      during treatment and decrease dialysis efficacy. Measurements of cardiovascular
      hemodynamics and urea kinetics were performed in 15 patients (56 studies) during
      dialysis, using a blood temperature monitor with control of dialysate
      temperature. Dialysate temperature was adjusted to either lower the core
      temperature or raise the core temperature by, respectively, producing negative
      heat-energy exchange (cooled dialysis) or keeping heat-energy exchange in the
      extracorporeal circuit neutral (thermoneutral dialysis) so that energy was not
      transferred to or from the patient. Each subject was studied on both protocols,
      thereby allowing each individual to act as his own control. In cooled dialysis,
      heat-energy exchange in the extracorporeal circuit was -266+/-15 kJ per
      treatment, and dialysate temperature averaged 35.7+/-0.02 degrees C. In
      thermoneutral dialysis, heat-energy exchange in the extracorporeal circuit
      averaged 5+/-31 kJ per treatment, and dialysate temperature averaged 37.1+/-0.02
      degrees C. Dialysate cooling resulted in a reduction in mean body temperature
      compared with thermoneutral therapy (-0.22+/-0.04 versus +0.31+/-0.05 degrees C).
      Cooling resulted in a greater increase in peripheral vascular resistance index
      (+515+/-160 versus + 114+/-92 dyn.sec/cm5 per m2), an increase in mean arterial
      pressure (+4+/-3 versus -4+/-4 mmHg), a reduction in the maximum intradialytic
      fall in mean arterial pressure (-10+/-2 versus -18+/-3, mmHg), and a reduction in
      staff interventions for hypotension or dialytic symptoms (6 of 28 versus 12 of 28
      studies). These differences occurred without differences in the change in blood
      volume (-14.3+/-1.8% versus -13.9+/-2.2%) or cardiac index (-0.4+/-0.1 versus 
      0.4+/-0.2, L/min per m2). Urea rebound (37+/-4% versus 38+/-3%) and effective
      Kt/V (1.29+/-0.05 versus 1.32+/-0.06) were not different between groups. Thus,
      body temperature cooling can be used to stabilize BP and reduce intradialytic
      events requiring staff intervention without compromising the efficacy of
      treatment in high-efficiency dialysis.

PMID- 9596087
TI  - The cost of caring for end-stage kidney disease patients: an analysis based on
      hospital financial transaction records.
AB  - The costs of care for end-stage renal disease patients continue to rise because
      of increased numbers of patients. Efforts to contain these costs have focused on
      the development of capitated payment schemes, in which all costs for the care of
      these patients are covered in a single payment. To determine the effect of a
      capitated reimbursement scheme on care of dialysis patients (both hemodialysis
      [HD] and peritoneal dialysis [PD]), complete financial records (all
      reimbursements for inpatient and outpatient care, as well as physician
      collections) of dialysis patients at a single medical center over 1 year were
      analyzed. For the period from July 1994 to July 1995, annualized cost per
      dialysis patient-year averaged $63,340, or 9.8% higher than the corrected
      estimate from the U.S. Renal Data Service (USRDS; $57,660). The "most expensive"
      25% of patients engendered 44 to 48% of the total costs, and inpatient costs
      accounted for 37 to 40% of total costs. Nearly half of the inpatient costs
      resulted from only two categories (room charges and inpatient dialysis), whereas
      other categories each made up a small fraction of the inpatient costs. PD
      patients were far less expensive to care for than HD patients, due to reduced
      hospital days and lower cost of outpatient dialysis. Care for a university-based
      dialysis population was only slightly more expensive than estimates predicted
      from the USRDS. These results validate the USRDS spending data and suggest that
      they can be used effectively for setting capitated rates. Efforts to control
      costs without sacrificing quality of care must center on reducing inpatient
      costs, particularly room charges and the cost of inpatient dialysis.

PMID- 9596088
TI  - Comparative strategies to induce long-term graft acceptance in fully allogeneic
      renal versus cardiac allograft models by CD28-B7 T cell costimulatory blockade:
      role of thymus and spleen.
AB  - Blocking CD28-B7 T cell costimulatory activation by the fusion protein CTLA4Ig
      prevents rejection and induces long-term graft acceptance in various experimental
      transplant models. There are reported differences in the efficacy of CTLA4Ig in
      renal and cardiac rodent allograft models, but it is not clear whether these are
      due to the strain or species differences investigated in the different studies
      reported. This study investigates the effect of blocking CD28-B7 T cell
      costimulation with murine CTLA4Ig in rat models of acute renal and cardiac
      allograft rejection models, using the same complete major histocompatibility
      complex-incompatible strain combination. A single injection of murine CTLA4Ig 2 d
      after engraftment was able to induce long-term graft acceptance (> 100 d) in 54%
      of Lewis rat recipients of Wistar-Furth kidneys. Transferring this protocol into
      the acute Wistar-Furth to Lewis heart allograft model resulted in a mean graft
      survival time of 24.7+/-16.9 d, and all grafts were ultimately rejected. Only
      concomitant injection of donor cells (4 x 10(7) splenocytes) plus a single
      injection of CTLA4Ig on the day of transplant could induce long-term graft
      acceptance in 50% of animals. In both the cardiac and renal transplant models,
      the thymus and spleen were required for induction of tolerance. The maintenance
      phase of tolerance, however, did not require an intact thymus but did require the
      presence of a spleen. These data have important clinical applicability because
      human studies with T cell costimulatory blockade are being planned.

PMID- 9596089
TI  - Dialysis dose: higher is better.

PMID- 9596090
TI  - The ASN and public policy. American Society of Nephrology.

PMID- 9596091
TI  - Chloride and fluid secretion in polycystic kidney disease.

PMID- 9596092
TI  - Nephrolithiasis.

PMID- 9596093
TI  - The Na concentration of the macula densa cells as a factor regulating glomerular
      filtration rate (micropuncture studies). 1965.

PMID- 9596094
TI  - Banning tobacco advertisements: is there a question?

PMID- 9596095
TI  - Pulmonary rehabilitation in chronic obstructive pulmonary disease.

PMID- 9596096
TI  - Investigation and assessment of airway and lung inflammation: we now have the
      tools, what are the questions?

PMID- 9596097
TI  - Methods of examining induced sputum: do differences matter?
AB  - Analysis of induced sputum has been proposed as a direct, relatively noninvasive
      method for the evaluation of airway inflammation in diseases such as asthma or
      chronic obstructive pulmonary disease (COPD). An important question in the
      validation of this technique concerns the potential influence of differences in
      the methods of examining sputum. Up to the present time, two basic techniques for
      processing sputum have been described. The first approach consists of selecting
      all viscid portions from the expectorated sample, whereas the second approach
      processes the whole expectorate, containing sputum plus saliva. Both processing
      techniques have been shown to provide valid and reliable data on the composition
      of the cellular and soluble fraction of induced sputum. From the data currently
      available, it would therefore appear that the usefulness of induced sputum as a
      method for assessing airway inflammation is not influenced by differences in the
      methods currently used for examining sputum.

PMID- 9596098
TI  - Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in
      severe pneumonia.
AB  - The aim of the present study was to further characterize the role of alveolar
      macrophages (AM) in acute human lung inflammation by evaluating their capacity to
      produce pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha,
      interleukin (IL)-6 and IL-8. Patients with severe community-acquired pneumonia
      (CAP; n=12) and healthy volunteers (n=10) underwent bronchoalveolar lavage (BAL).
      AM were separated to high purity (>96%) using fluorescence-activated cell
      sorting. We determined the TNF-alpha, IL-6 and IL-8 cytokine gene expression in
      AM ex vivo using semiquantitative reverse transcriptase polymerase chain reaction
      (RT-PCR). Moreover, we measured in vitro unstimulated, lipopolysaccharide (LPS)-
      and LPS/interferon-gamma inducible TNF-alpha, IL-6 and IL-8 cytokine release and
      evaluated samples of BAL fluids for the same pro-inflammatory cytokines using an
      enzyme-linked immunosorbent assay (ELISA). We found increased TNF-alpha, IL-6 and
      IL-8 messenger ribonucleic acid (mRNA) levels in AM from CAP patients that were
      significantly elevated only for IL-8. When challenged with endotoxin in vitro, AM
      obtained from CAP patients showed a strongly reduced potential to release TNF
      alpha and IL-6 compared to healthy controls, whereas IL-8 secretion did not
      differ significantly between groups. Moreover, stimulation of AM from CAP
      patients with LPS plus IFN-gamma augmented TNF-alpha and IL-6 cytokine release to
      near normal levels. Interestingly, no TNF-alpha protein was measured in BAL
      samples from CAP patients, whereas IL-6 and IL-8 protein levels were found to be
      significantly increased. Together, highly purified alveolar macrophages from
      community-acquired pneumonia patients show relatively low ex vivo tumour necrosis
      factor-alpha and interleukin-6 but not interleukin-8 messenger ribonucleic acid
      levels that are associated with a decreased pro-inflammatory cytokine release in
      vitro which, however, can be restored by concurrent interferon-gamma stimulation.

PMID- 9596099
TI  - Surfactant changes during experimental pneumocystosis are related to Pneumocystis
      development.
AB  - Pneumocystosis-related surfactant changes have been reported in both humans and
      corticosteroid-treated experimental hosts. As corticosteroids induce an increase
      in pulmonary surfactant, some findings could be considered as controversial. The
      aim of this study was to investigate whether the surfactant composition changes
      during experimental pneumocystosis were related to the Pneumocystis development.
      In this work two corticosteroid-untreated animal models were used: rabbits, which
      develop spontaneous pneumocystosis at weaning; and severe combined
      immunodeficiency mice, which were intranasally inoculated with Pneumocystis
      carinii. Surfactant phospholipid and protein content was explored by
      bronchoalveolar lavage. The in vitro effect of surfactant on P. carinii growth
      was also explored. In the two models, the surfactant phospholipid/protein ratio
      was significantly increased, whereas parasite rates were low. This ratio
      decreases with the slope increase of the parasite growth curve. These early
      surfactant changes suggested that Pneumocystis proliferation requires alveolar
      lining fluid changes, and that normal surfactant is not suitable for parasite
      development. In this way, in vitro experiments presented here have revealed an
      inhibitory effect of synthetic or seminatural surfactants on the P. carinii
      growth. Further studies are needed to determine how Pneumocystis induces the
      reported early modifications of the surfactant, and why the parasite development
      is inhibited by pulmonary surfactant.

PMID- 9596100
TI  - Changes in lung lymphocyte populations reflect those seen in peripheral blood in
      HIV-1 positive individuals.
AB  - We have investigated the level of lymphocytosis present in the lung of human
      immunodeficiency virus (HIV)-1+ infected patients with and without pulmonary
      disease and how changes in natural killer (NK), B and T-cells seen in peripheral
      blood (PB) compare with those seen in bronchoalveolar lavage fluid (BALF).
      Lymphocyte subpopulations and their expression of activation, cytotoxic markers
      and memory status were characterized by triple immunofluorescence. Macrophages
      accounted for over 80% of the BAL cells. Only three out of 72 patients had a
      lymphocyte percentage >30%. No statistically significant differences in the
      relative proportions of NK, CD4 and CD8 populations were seen in BALF when
      compared to PB, except for a twofold increase in the percentage of activated CD8
      cells in BALF. The only differences in BALF populations between the HIV-1+ groups
      were a lower percentage of CD4+ cells, and a higher percentage of activated CD8+
      cells in the patients with pneumonitis. In the present cohort of patients there
      was little evidence for an overall lymphocytosis in bronchoalveolar lavage fluid
      of HIV-1+ subjects. Changes observed in lymphocyte subsets of bronchoalveolar
      lavage fluid populations reflected those in peripheral blood, and were similar
      for patients with and without pneumonitis. Evidence of increased CD8 subset
      activity in bronchoalveolar lavage fluid did, however, emerge.

PMID- 9596101
TI  - Platelet-derived growth factor expression in primary pulmonary hypertension:
      comparison of HIV seropositive and HIV seronegative patients.
AB  - Primary pulmonary hypertension (PPH) is characterized by intimal fibrosis and
      cell proliferation (including fibroblasts, smooth muscle and endothelial cells)
      in the distal pulmonary arterial tree. Considerable interest has been generated
      by recent reports of PPH in human immunodeficiency virus (HIV)-1-infected
      individuals. Although the lack of evidence for a pulmonary artery infection has
      suggested that in such cases HIV may act through mediator release rather than by
      direct endothelial infection, the mechanisms underlying HIV-associated PPH remain
      poorly defined. Platelet-derived growth factor (PDGF) has the ability to induce
      smooth muscle cell and fibroblast proliferation and migration. Given these
      considerations, we have attempted to document a possible role for PDGF in PPH
      occurring in HIV seropositive and seronegative patients. Using semiquantitative
      polymerase chain reaction (PCR), PDGF A-chain messenger ribonucleic acid (mRNA)
      expression was analysed in surgical lung biopsies from 13 HIV seronegative
      patients and one HIV seropositive patient, all displaying severe PPH. In
      parallel, lung samples from two patients with HIV-1-associated PPH were studied
      by immunohistochemistry and in situ hybridization. Results were compared to those
      obtained in three HIV-1-infected individuals with no pulmonary complication (as
      demonstrated by clinical, radiological, bacteriological, and necropsy findings)
      and five control lung biopsies. As compared to controls, PDGF A-chain mRNA
      expression is elevated in lung biopsies from patients displaying PPH (p=0.029).
      In HIV-1-associated PPH, interstitial perivascular cells expressing PDGF A-chain
      mRNA and protein could be detected by in situ hybridization and
      immunohistochemistry, respectively. Platelet-derived growth factor expression is
      elevated in lung biopsies of patients displaying primary pulmonary hypertension.
      Growth factors such as platelet-derived growth factor may play a part in the
      initiation and/or progression of primary pulmonary hypertension.

PMID- 9596102
TI  - Prognostic factors in restoration of pulmonary flow after submassive pulmonary
      embolism: a multiple regression analysis.
AB  - Defects as evaluated by lung perfusion scans may persist even 6 months after
      pulmonary embolism (PE), when treatment is withdrawn. The aim of this study was
      to evaluate the effect of several potential factors on the resolution of lung
      perfusion defects, both during the first days and at 6 months, when patients were
      discharged. In a retrospective follow-up cohort study we included 102 patients
      with PE, diagnosed lung from a ventilation/perfusion (V'/Q') scan, following
      Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria,
      together with a phlebographic study of lower extremities or angiography. Lung
      perfusion scan was performed at diagnosis, and in two follow-up evaluations, at 7
      10 days and at 6 months. Potential factors studied were: age; sex; presence of
      underlying cardiac or pulmonary disease; venous insufficiency; alveolar-arterial
      pressure difference for oxygen; delay in diagnosis; abnormalities in
      electrocardiogram or chest radiograph; and the size of defects as shown in lung
      perfusion scans. All factors were studied with regards to the size of the defects
      at the two follow-up evaluations, through a univariate statistical analysis and
      two multiple stepwise regression analysis. Multivariate statistical analysis
      selected four factors: size of defects at diagnosis; prior cardiopulmonary
      disease; delay in diagnosis; and sex, as synergistic variables to predict defect
      size at 7-10 days. On the other hand, the defect size at 7-10 days was the only
      variable selected as a predictor of the size of defects at 6 months. Resolution
      of pulmonary defects during the first days after diagnosis of pulmonary embolism
      is influenced by the initial defect size, prior cardiopulmonary diseases and sex.
      The size of residual defects at 6 months depends mainly on the size of defects at
      7-10 days.

PMID- 9596103
TI  - Individual lung blood flow during unilateral hypoxia: effects of inhaled nitric
      oxide.
AB  - We hypothesized that the diversion of blood away from a hypoxic lung to the
      opposite oxygenated lung can be enhanced by inhaling nitric oxide (NO) into the
      oxygenated lung. We measured individual lung blood flow when 50 ppm NO was
      selectively inhaled to: a hyperoxic lung during contralateral hypoxia; a normoxic
      lung during bilateral normoxia; and a hyperoxic lung during bilateral hyperoxia.
      Twenty two patients with healthy lungs were studied during intravenous
      anaesthesia. The lungs were separately and synchronously ventilated. The relative
      perfusion of each lung was assessed by the inert gas elimination technique.
      Unilateral hypoxic (inspiratory oxygen fraction (FI,O2) 0.05) ventilation during
      contralateral hyperoxia reduced the perfusion of the hypoxic lung from a mean
      (SD) of 47 (9)% of cardiac output (Q'), to 30 (7)% (p<0.001) of Q'. NO inhalation
      to the hyperoxic lung increased its blood flow from 70 (7)% to 75 (6)% (p<0.05)
      of Q', and reduced the blood flow to the hypoxic lung to 25 (6)% (p<0.05).
      Unilateral NO inhalation during bilateral normoxia or hyperoxia had no effect on
      pulmonary blood flow distribution. Nitric oxide inhalation to a hyperoxic lung
      increases the perfusion to this lung by redistribution of blood flow if the
      opposite lung is hypoxic.

PMID- 9596104
TI  - Regulation of adrenergic nerve-mediated contraction of canine pulmonary artery by
      K+ channels.
AB  - The aim of the present study was to investigate the role of certain subtypes of
      K+ channels in nerve-evoked contractions of pulmonary artery in vitro. The lobar
      or segmental pulmonary arteries were dissected from dogs, cut into ring segments,
      and the contractile responses to electrical field stimulation (EFS) and
      noradrenaline were measured under isometric conditions. Addition of iberiotoxin,
      a big conductance Ca2+-activated K+ channel blocker, and apamin, a small
      conductance Ca2+-activated K+ channel blocker, did not change the resting tension
      but augmented the contractile responses to EFS, so that the electric stimulus
      frequency required to produce a half-maximal contraction (ES50) was decreased
      from 18.2+/-3.5 to 7.4+/-2.3 Hz (p<0.01) and from 16.8+/-2.2 to 11.4+/-2.0 Hz
      (p<0.05), respectively, whereas glibenclamide, an adenosine triphosphate (ATP)
      sensitive K+ channel blocker, had no effect. In contrast, none of the K+ channel
      blockers altered the contractile response to noradrenaline. Incubation of tissues
      with iberiotoxin and apamin increased the release of 3H-noradrenaline evoked by
      EFS. We conclude that big conductance Ca2+-activated K+ channels and small
      conductance Ca2+-activated K+ channels may play a role in the regulation of
      adrenergic neurotransmission in the pulmonary artery, probably by inhibiting the
      exocytotic release of noradrenaline from the adrenergic nerve terminals.

PMID- 9596105
TI  - Effects of corticosteroids on epithelial structure and smooth muscle function of
      rat trachea.
AB  - Corticosteroids, efficient drugs for the treatment of severe asthma, may have
      numerous side effects. We investigated the effects of 7 days of treatment with
      triamcinolone (1.2 mg x kg(-1) x day(-1)) on the epithelial structure, tracheal
      smooth muscle cross-sectional area and contractility in the rat. The
      corticosteroid-injected rats were compared to pair-fed, and pair-weighed animals.
      Histological studies were performed on transverse sections of glutaraldehyde
      fixed tracheal blocks embedded in plastic. In the preparations taken from
      corticosteroid-injected, pair-fed and pair-weighed animals, pharmacological
      stimulation with single (10(-3) M) or cumulative (10(-8)-10(-3) M) concentrations
      of carbachol (in corticosteroid-injected and pair-fed animals), either inside
      (In) or outside (Out) of the tracheal lumen, was performed and contractions of
      the tracheal smooth muscle were recorded. We found that triamcinolone
      administration: 1) reduced the number of epithelial cells and the tracheal smooth
      muscle cross-sectional area; 2) induced a decrease in maximal tension (Tmax (g);
      Out: 2.42+/-0.17, 1.03+/-0.1 in pair-fed and corticosteroid-injected,
      respectively; In: 2.55+/-0.16, 1.1+/-0.16, respectively) without affecting the
      sensitivity of the tracheal smooth muscle; and 3) reduced the time required to
      reach 50% Tmax in carbachol (In) preparations. We conclude that the observed
      changes resulted from atrophy of tracheal smooth muscle induced by undernutrition
      and atrophy of tracheal smooth muscle and tracheal epithelium induced by
      corticosteroid treatment.

PMID- 9596106
TI  - Long- and short-acting beta2 adrenoceptor agonists: interactions in human
      contracted bronchi.
AB  - The aim of this study was to systematically compare the interaction of the long
      acting beta2-adrenoceptor agonists formoterol and salmeterol with short-acting
      beta2-adrenoceptor agonists in contracted human bronchi. Human bronchi were
      obtained at thoracotomy from patients with lung cancer. Formoterol or salmeterol
      at concentrations inducing up to 92 and 94% of their maximal relaxant effect,
      respectively, were added to bronchial rings contracted with carbachol (10(-6) M).
      After a time period of 30 min, concentration-response curves for the short-acting
      beta2-adrenoceptor agonists, salbutamol, terbutaline, isoprenaline and fenoterol
      were recorded. Administration of equieffective concentrations of salmeterol and
      formoterol, resulted in only salmeterol inducing a shift to the right of
      isoprenaline, terbutaline, fenoterol and salbutamol concentration-response
      curves. The rank order of shift was salbutamol > fenoterol > terbutaline >
      isoprenaline. Formoterol, up to concentrations of 3x10(-9) M induced submaximal
      relaxation resulting in no shift in short-acting beta2-adrenoceptor agonist
      concentration-response curves. Salmeterol but not formoterol appears to
      antagonize the relaxation of human contracted bronchi induced by short-acting
      beta2-agonists. These results obtained in vitro cannot be translated in clinical
      terms. This study, however, highlights the need for clinical studies on the
      interaction of long-acting and short-acting beta2-adrenoceptor agonists in acute
      severe asthma.

PMID- 9596107
TI  - Polymorphism of the beta2-adrenoceptor and the response to long-term beta2
      agonist therapy in asthma.
AB  - Polymorphisms affecting amino acids 16 and 27 of the beta2-adrenoceptor alter
      receptor regulation in vitro. Whether these polymorphisms alter the response to
      beta2-agonist therapy in asthma is unknown. In a previous study of 64 asthmatics,
      most experienced a deterioration in asthma control during regular inhaled beta2
      agonist (fenoterol) treatment, while a minority improved. We have determined the
      beta2-adrenoceptor genotypes in these subjects, to establish whether changes in
      asthma control during the earlier study were influenced by beta2-adrenoceptor
      polymorphism. The genotypes coding for amino acids 16 and 27 were identified in
      60 subjects using allele-specific polymerase chain reaction. The effects of
      regular beta2-agonist treatment on asthma control were compared between
      genotypes. There was no association between genotype and change in overall asthma
      control during regular beta2-agonist treatment. Only two of 10 markers of asthma
      control showed changes that were significantly associated with genotype: subjects
      homozygous for glycine at position 16 had no increase in bronchial responsiveness
      to methacholine during regular treatment; subjects homozygous for glutamic acid
      at position 27 had no increase in evening peak expiratory flow rates during
      regular treatment. These differences are the opposite of those that would have
      been predicted by the results of in vitro studies. In these subjects, the
      deleterious response to regular inhaled beta2-agonist treatment was not related
      to beta2-receptor polymorphism.

PMID- 9596108
TI  - Serum eosinophil cationic protein measurements in the management of perennial and
      periodic asthma: a prospective study.
AB  - We performed a prospective study in order: 1) to determine whether a correlation
      could be found between serum eosinophil cationic protein (ECP) levels and
      clinical and functional status in perennial asthmatics during a 5 month
      prospective study; and 2) to evaluate the relationship between allergic exposure
      and ECP levels in periodic asthmatics. Two groups of asthmatic patients were
      selected: a group of acutely ill perennial asthmatics and a group of periodic
      asthmatics. The acutely ill perennial asthmatics (n=22, mean age=39.4 yrs) were
      included on the basis of hospitalization for acute asthma. At the end of the
      hospitalization, there was a 5 month follow-up of clinical, functional and
      medication scores, as well as eosinophil counts and ECP levels. The periodic
      asthmatic group was composed of asthmatics sensitized to birch and tree pollens
      (n=10, mean age=33.8 yrs). The same measurement were performed on this group,
      before, during and after the pollen season. Under corticosteroid treatment in the
      acutely ill patients, there was a significant decrease in serum ECP levels
      between the first day of hospitalization and the day of discharge (mean: 23.2
      microg x L(-1) and 9.5 microg x L(-1), respectively; p=0.006). No correlation was
      found between the clinical status, functional status and serum ECP levels during
      the 5 month follow-up. A significant increase in ECP levels was found in periodic
      asthmatics during the pollen season. Our results suggest that serum eosinophil
      cationic protein is a useful marker of allergen exposure and of acute asthma
      treatment. This could be of importance in the prevention and follow-up of
      allergic asthma; the value of serum eosinophil cationic protein measurements in
      the day-to-day management of adult asthmatics needs to be further clarified.

PMID- 9596109
TI  - An undetected burden of asthma in Italy: the relationship between clinical and
      epidemiological diagnosis of asthma.
AB  - This study aimed to compare questions and tests used in asthma epidemiology with
      clinical diagnosis of current asthma and to assess the extent of undiagnosed
      asthma in Italy. Thus, 811 attenders to the second stage of the European
      Community Respiratory Health Survey were classified by panels of respiratory
      physicians as current asthmatics or not. Among those with a clinical diagnosis of
      asthma (n=105), 69% reported current wheezing and 68% asthma in their lifetime
      (ever asthma), while asthma attacks in the previous year and/or current treatment
      for asthma (self-reported current asthma) were mentioned by only 37%. Thirty two
      per cent did not mention asthma at any time, but nevertheless presented a rate of
      hospitalization close to that of people with self-reported current asthma. On the
      other hand, almost no subjects labelled nonasthmatics by clinicians (n=706)
      presented self-reported current asthma (99.7%), while some reported ever asthma
      (5%) or current wheezing (9%). A model simulation showed that, in its usual range
      (0-15%), asthma prevalence is markedly overestimated by the question on wheezing
      and underestimated by the questions on self-reported current asthma, with respect
      to clinical judgement. Prevalence estimates close to those obtained by clinical
      judgement were achieved by combining asthma-like symptoms in the previous year
      with the results of lung function and allergological tests, but especially by
      using the single question on ever asthma. In conclusion, the present results
      suggest that the question on ever asthma gives prevalence estimates close to
      those obtained by clinical judgement and that asthma is greatly underdiagnosed in
      Italy.

PMID- 9596110
TI  - The effects of static charge in spacer devices on glucocorticosteroid aerosol
      deposition in asthmatic patients.
AB  - Electrostatic charge in plastic spacer devices has been shown in vitro to reduce
      delivery of asthma medications intended for inhalation, but the effect of static
      charge on in vivo drug deposition is unknown. A six-way randomized crossover
      study was conducted in 10 mild asthmatic patients. Two plastic spacers (Nebuhaler
      and Volumatic) and one metal spacer (Nebuchamber) were tested. The spacers were
      used either "primed" or "unprimed". Priming was performed by firing 20 doses of
      placebo aerosol into a new spacer, hence coating the inner surface with
      surfactant and minimizing static charge. Unprimed spacers were new and were not
      treated. Pressurized aerosol canisters delivering budesonide (200 microg
      Pulmicort) were radiolabelled with the radionuclide 99mTc and lung deposition was
      measured by gamma scintigraphy. The radiolabel was shown to be a valid marker for
      the drug substance prior to the clinical phase of the study. Priming
      significantly increased mean whole lung deposition following inhalation from
      plastic spacers (Nebuhaler primed 37.7% and unprimed 26.7%, p=0.01; Volumatic
      primed 32.0% and unprimed 22.1%, p=0.02). Priming had no effect on the mean whole
      lung deposition following inhalation from the Nebuchamber (primed 33.5% and
      unprimed 32.9%). Lung deposition in vivo from plastic spacer devices will vary
      according to the electrostatic charge on the spacer walls. Priming reduces
      retention of drug on plastic spacer devices and increases lung deposition. Metal
      spacers are not susceptible to static charge, which should result in more
      predictable lung deposition.

PMID- 9596111
TI  - Long-term reduction in asthma morbidity following an asthma self-management
      programme.
AB  - The adult "credit card" asthma self-management plan has been shown to be an
      effective and acceptable system for reducing asthma morbidity when introduced as
      part of a 6 month community-based asthma programme. The aim of the present study
      was to assess the effectiveness of the credit card plan 2 yrs after the end of
      the programme. Markers of asthma morbidity and use of medical services were
      compared during the 12 months before enrolment, and 2 yrs after completing the 6
      month asthma programme. Of the 69 participants who originally enroled in the 6
      month asthma programme, 58 were surveyed 2 yrs after completion of the programme.
      These participants showed a significant improvement in all but one of the asthma
      morbidity measures. The proportion waking most nights with asthma in the previous
      12 months decreased from 29 to 9% (p=0.02), emergency visits to a general
      practitioner decreased from 43 to 16% (p=0.001), hospital emergency department
      visits with asthma decreased from 19 to 5% (p=0.02) and hospital admissions
      decreased from 17 to 5% (p=0.04). Only 24% of patients reported that they usually
      monitored their peak flow rate daily, but this increased to 73% during a "bad"
      attack of asthma. A long-term reduction in asthma morbidity and requirement for
      acute medical services can result following the introduction of the adult credit
      card asthma self-management plan. Adult patients with asthma are most likely to
      undertake peak flow monitoring preferentially during periods of unstable asthma,
      rather than routinely during periods of good control.

PMID- 9596112
TI  - Effects of a 5-lipoxygenase inhibitor, ABT-761, on exercise-induced
      bronchoconstriction and urinary LTE4 in asthmatic patients.
AB  - The novel 5-lipoxygenase (5-LO) inhibitor, ABT-761, was investigated for its
      effect on exercise-induced bronchoconstriction in asthmatic subjects. The
      relationship between 5-LO inhibition and effects on the response of the airways
      to exercise was examined. In a double-blind, randomized, crossover clinical
      trial, 10 patients with mild to moderate persistent asthma (who exhibited a fall
      in forced expiratory volume in one second (FEV1) > or = 20% following
      standardized exercise challenge) received 200 mg ABT-761 or matched placebo,
      orally, 5 h prior to exercise on two study days, 7-10 days apart. Lung function,
      urinary leukotriene E4 (LTE4) and ex vivo calcium ionophore-stimulated LTB4
      release in whole blood were measured prior to dosing, prior to exercise and at
      various time points up to 4 h post-exercise. The mean (SD) maximal percentage
      fall in FEV1 after exercise was 27.1 (12)% on placebo and 19.9 (10)% on ABT-761
      days, respectively (p<0.05). Post-exercise fall in FEV1 was significantly
      attenuated at 5, 10, 15 and 30 min after exercise and the mean area under curve,
      representing the overall effect of exercise from 0-45 min post-challenge, was
      also significantly attenuated by ABT-761 (p<0.001). Ex vivo LTB4 release was
      inhibited by more than 80% throughout the 4 h post-exercise period, indicating
      that 5-LO was extensively inhibited at all time points. Urinary LTE4 in the post
      exercise period was significantly lower after ABT-761 day than after placebo
      (40.1 (17.6) versus 89.8 (58.2) pg x mg creatinine(-1); p<0.05). Inhibition of
      LTB4 release in ABT-761-treated patients correlated positively with the
      attenuation of post-exercise FEV1 decline (r=0.711; p<0.05). We conclude that ABT
      761 is effective in suppressing exercise-induced bronchoconstriction and that
      this protection is related quantitatively to the degree of 5-lipoxygenase
      inhibition.

PMID- 9596113
TI  - Effect of thromboxane A2 inhibitors on allergic pulmonary inflammation in mice.
AB  - Thromboxane (Tx)A2 synthase inhibitors and thromboxane prostanoid (TP) receptor
      antagonists have been developed as anti-asthma drugs. TxA2 may contribute to
      airflow limitation and bronchial hyperresponsiveness, and these compounds have
      been demonstrated to improve them. However, it is not known whether TxA2 is
      involved in bronchial inflammation. To address this question, we explored the
      influences of OKY-046 (a TxA2 synthase inhibitor) and S-1452 (a TP receptor
      antagonist) on eosinophilic inflammation of the airways using a murine model.
      BALB/c mice sensitized with ovalbumin and challenged by repeated exposure to
      ovalbumin yielded marked eosinophilia in bronchoalveolar lavage fluid (BALF).
      Treatment with either compound significantly reduced the number of total cells
      and eosinophils in BALF in a dose-dependent manner. The production of interleukin
      (IL)-5, IL-2 and interferon (IFN)-gamma by antigen-stimulated splenic mononuclear
      cells (SMNC) was significantly decreased in mice treated with either compound
      compared to that in untreated mice. Furthermore, both compounds inhibited
      proliferation and cytokine production of SMNC in vitro. These results suggest
      that both OKY-046 and S-1452 are capable of inhibiting production of cytokines,
      which in turn inhibits eosinophil infiltration into the murine airway. Thus, both
      thromboxane A2 synthesis inhibitors and thromboxane prostanoid antagonists may be
      effective as anti-inflammatory drugs in the treatment of asthma.

PMID- 9596114
TI  - Local cytokine messenger ribonucleic acid expression and in vitro allergic late
      phase responses in Brown-Norway rats.
AB  - The events subsequent to antigen challenge in allergic asthmatics involve the
      synthesis of pro-inflammatory cytokines. However, little is known how cytokine
      gene activation prior to allergen challenge may influence this series of events,
      nor how cytokine gene expression is related to antigen-induced alterations in
      lung function. Using a novel in vitro explant technique, we hypothesized that the
      local expression of cytokines influenced the development of antigen-induced late
      onset airway responses, and that alterations in cytokine messenger ribonucleic
      acid (mRNA) expression were associated with antigen-induced changes in airway
      luminal area. Explants were prepared from excised lungs of ovalbumin-sensitized
      Brown-Norway rats. Airways were challenged by direct application of ovalbumin or
      an irrelevant control antigen. Cryostat sections of explants were used for in
      situ hybridization and mRNA for interleukin (IL)-2, IL-4 and interferon (IFN)
      gamma were detected using radiolabelled probes. We found that the presence of
      high numbers of cells expressing IFN-gamma and IL-2 mRNA within the airways
      attenuated the development of antigen-induced late airway responses in sensitized
      rat lung explants. Furthermore, we observed that cytokine mRNA for IL-4 was
      significantly increased following allergen exposure in sensitized lung explants
      exhibiting late airway responses. This study implicates the local expression of
      interferon-gamma and interleukin-2 messenger ribonucleic acid in the failure of
      sensitized rat lung explants to exhibit late airway responses, and provides
      evidence linking local interleukin-4 messenger ribonucleic acid expression to the
      sequelae of events occurring as a result of antigen exposure within the airways.

PMID- 9596115
TI  - Leucocyte kinesis in blood, bronchoalveoli and nasal cavities during late
      asthmatic responses in guinea-pigs.
AB  - Recently, we reported a reproducible model of asthma in guinea-pigs in vivo,
      which developed a late asthmatic response (LAR) as well as an early response. In
      this study, time-related changes in the occurrence of the LAR and leucocyte
      kinesis were assessed. Furthermore, the state of the activation of eosinophils
      that migrated into the lower airways was characterized in vitro. Guinea-pigs were
      alternately sensitized/challenged by inhalation with aerosolized ovalbumin
      adsorbed on aluminium hydroxide and ovalbumin alone, once every 2 weeks. At
      defined times before and after the fifth challenge, airway resistance was
      measured, blood was drawn and bronchoalveolar lavage (BAL) and nasal cavity
      lavage (NCL) were performed. Superoxide anion (.O2-) production of eosinophils
      was measured with cytochrome c. Occurrence of LAR and considerable increases in
      circulating eosinophils coincided with each other 5-7 h after the challenge.
      After 7 h, eosinophil infiltrations into bronchoalveolar spaces were observed.
      The capacity of eosinophils from the sensitized animals to produce .O2- was
      higher than those from the non-sensitized ones, when eosinophils were stimulated
      by platelet-activating factor. Although an increased number of eosinophils in the
      NCL fluid was observed, it was much less than that in the BAL fluid. Thus, it has
      been concluded that eosinophilia in the blood and the lung may participate in the
      occurrence of the late asthmatic response, which is thought to be preferentially
      evoked in the lower airways in guinea-pigs in vivo.

PMID- 9596116
TI  - Lung diffusing capacity and exercise in subjects with previous high altitude
      pulmonary oedema.
AB  - Subjects with a history of high-altitude pulmonary oedema (HAPE) have increased
      pulmonary artery pressure and more ventilation-perfusion (V'A/Q') inhomogeneity
      with hypoxia and exercise. We used noninvasive methods to determine whether there
      are differences in the pulmonary diffusing capacity for carbon monoxide (DL,CO)
      and cardiac output (Q') during exercise, indicative of a more restricted
      pulmonary vascular bed in subjects with a history of HAPE. Eight subjects with
      radiographically documented HAPE and five controls with good altitude tolerance
      had standard pulmonary function testing and were studied during exercise at 30
      and 50% of normoxic maximal oxygen consumption (V'O2) at an inspiratory oxygen
      fraction of 0.14 and 0.21. DL,CO and Q' were measured by CO and acetylene
      rebreathing techniques. HAPE-resistant subjects had 35% greater functional
      residual capacity than HAPE-susceptible subjects. Vital capacity and total lung
      capacity were also 7-10% greater. There were no differences in airflow rates or
      resting diffusing capacity. However, DL,CO in HAPE-susceptible subjects was lower
      in hypoxia and with exercise, and showed less increase (32 versus 49%) with the
      combined stimulus of hypoxic exercise. HAPE-susceptible subjects had smaller
      increases in stroke volume, Q', and ventilation during exercise. The findings are
      consistent with lower pulmonary vasoconstriction, greater vascular capacitance
      and greater ventilatory responsiveness during exercise in subjects who are
      resistant to high-altitude pulmonary oedema. Their larger lung volumes suggest a
      constitutional difference in pulmonary parenchyma or vasculature, which may be a
      determinant of high-altitude pulmonary oedema resistance.

PMID- 9596117
TI  - The association of respiratory symptoms and lung function with the use of gas for
      cooking. European Community Respiratory Health Survey.
AB  - The association of respiratory symptoms and lung function with the use of gas for
      cooking was examined using data collected as part of the European Community
      Respiratory Health Survey, an international multicentre study. Associations
      between gas cooking and respiratory symptoms and respiratory function were
      assessed by logistic and multiple regression models. Tests for interaction were
      used to examine whether the effect of gas cooking varied between centres and, as
      there was evidence for this, the average effects were estimated using standard
      methods for random effects meta-analysis. Data from 5,561 males and 6,029 females
      living in 23 centres in 11 countries were analysed. There was no significant
      association found between respiratory symptoms and gas cooking in males. In
      females the association between some respiratory symptoms and gas cooking varied
      between centres with an overall positive association with "wheeze in the last 12
      months" (odds ratio (OR) 1.24: 95% confidence interval (95% CI) 1.00-1.54) and
      "wheeze with breathlessness in the last 12 months" (OR 1.33: 95% CI 1.06-1.69).
      There was no evidence that atopy modified this association. Cooking with gas was
      associated with airways obstruction in both males and females although the
      differences failed to reach statistical significance. In some countries the use
      of gas for cooking is associated with respiratory symptoms suggestive of airways
      obstruction in females.

PMID- 9596118
TI  - Bronchopulmonary disease in Iranian housewives chronically exposed to indoor
      smoke.
AB  - Tobacco smoking is recognized as the main cause of chronic bronchitis followed by
      occupational exposure to dust, fumes and gases. Indoor inhalation of smoke is
      being investigated increasingly but mainly the acute morbidity has been described
      while the late features and complications which may lead to respiratory
      disability are less well known. Among the 388 female patients who were referred
      to the main Bronchoscopy Unit of Tehran University of Medical Sciences between
      1986 and 1995, 10 nonsmoking elderly housewives were found with chronic
      bronchopulmonary lesions characterized by widespread mucosal swelling and
      anthracotic plaques of the airways. Enquiry into their past history revealed
      massive exposure to smoke over many years whilst baking household rustic bread
      inside dwellings. No other source of air pollution was detected. The main
      clinicopathological features were respiratory disability due to chronic
      bronchitis with intracellular as well as extracellular black particles. As
      similar cases may present to medical practitioners even in affluent societies as
      a result of increasing amounts of immigrants from developing countries,
      recognition of these patients is important to avoid irrelevant diagnoses and
      unnecessary interventions.

PMID- 9596119
TI  - The effect of latent adenovirus 5 infection on cigarette smoke-induced lung
      inflammation.
AB  - The aim of this study was to test the hypothesis that latent adenovirus (Ad) 5
      infection increases the lung inflammation that follows a single acute exposure to
      cigarette smoke. A recently developed model of latent adenoviral infection in
      guinea-pigs was used. Twelve animals were infected with Ad5 (10(8) plaque-forming
      units) and 12 animals were sham-infected. Thirty five days later six Ad5-infected
      and six sham-infected animals were exposed to the smoke from five cigarettes. The
      remaining animals were used as controls for both infection and smoking. As
      markers of inflammation, the volume fraction of macrophages, T-lymphocytes,
      neutrophils and eosinophils were measured by quantitative histology. We found
      that latent Ad5-infection alone, doubled the number of macrophages in the lung
      parenchyma and that smoking alone, doubled the volume fraction of neutrophils in
      the airway wall and the volume fraction of macrophages in the lung parenchyma.
      Neither viral infection nor smoking, alone, had an effect on T-lymphocytes or
      eosinophils. However, the combination of viral infection and smoking doubled the
      T-lymphocyte helper cells and quadrupled the volume fraction of macrophages in
      the lung parenchyma. We conclude that in guinea-pigs, latent adenovirus 5
      infection increases the inflammation that follows a single acute exposure to
      cigarette smoke, by increasing the volume fraction of macrophages and T
      lymphocyte helper cells.

PMID- 9596120
TI  - Bronchial reactivity to cigarette smoke in smokers: repeatability, relationship
      to methacholine reactivity, smoking and atopy.
AB  - Bronchial reactivity to cigarette smoke (CBR) in a cross-section of 98 smokers
      has been investigated. All participants were subjects to skin-prick tests to
      common allergens, lung function measurements and bronchial challenges with
      methacholine and cigarette smoke. In 38 participants a rechallenge with
      cigarettes was performed 1 h after the first cigarette challenge. Lung function
      indices analysed were: forced expiratory volume in one second (FEV1); maximal
      expiratory flow at 75% of the forced vital capacity (MEF75%); and forced mid
      expiratory flow between 25 and 75% of the forced vital capacity (FEF(25-75%)).
      All participants were tested for asthma and allergy, and were required to provide
      information regarding respiratory symptoms, first degree relatives with asthma
      and allergy and smoking habits. A substantial decrease was seen in all lung
      function indices after 12 cigarette-smoke inhalations, but only FEV1 was related
      to other variables. The maximal mean percentage fall in FEV1 was 10%, which was
      directly related to the number of inhalations (p<0.05). In multiple regression
      analyses the percentage fall in FEV1 was directly related to: FEV1/vital capacity
      (VC) (p<0.01); to the asthmatic/bronchitic status (p<0.05); and to the
      accumulated and standardized cigarette consumption (p<0.05). The percentage fall
      in FEV1 bore no relationship to methacholine bronchial reactivity, sex or age and
      had a continuous distribution. The repeat challenge showed a smaller fall in FEV1
      compared to the first challenge after 12 cigarette smoke inhalations (p<0.05).
      The percentage fall in FEV1 correlated after the first and the repeat challenge
      (p<0.05). Repeatability of the challenge could not be determined in this study
      because of tachyphylaxis. Bronchial reactivity to cigarette smoke is a tobacco
      smoke-specific bronchial response. All participants responded and the response
      showed a continuous distribution. Bronchial reactivity to cigarette smoke may be
      of importance for symptoms and prognosis in chronic bronchitis and chronic
      obstructive pulmonary disease and should be studied in relation to the degree of
      accelerated lung function loss in smokers and other cigarette induced lung
      abnormalities.

PMID- 9596121
TI  - Short-term effect of winter air pollution on respiratory health of asthmatic
      children in Paris.
AB  - There is controversy as to whether low levels of air pollution affect the
      symptoms and lung function in asthma. We addressed this by examining the short
      term effects of winter air pollution on childhood asthma in Paris. We performed a
      6 month follow-up of 84 medically diagnosed asthmatic children classified into
      two groups of severity. The outcomes included incidence and prevalence of asthma
      attacks, symptoms and use of supplementary beta2-agonists, peak expiratory flow
      (PEF) value and its variability. The statistical analysis controlled the lack of
      independence between daily health outcomes, trends and meteorology. Air pollution
      was associated with an increase in reports and duration of asthma attacks and
      asthma-like symptoms in mild asthmatic children. The strongest association was
      the risk of asthma attack for an increase of 50 microg x m(-3) of sulphur dioxide
      (SO2) on the same day (odds ratio (OR)=2.86). Maximum reduction in morning peak
      expiratory flow (PEF) (5%) and maximum increase in PEF variability (2%) were
      observed at a lag of 3 days for an increase of 50 microg x m(-3) of SO2 in the
      subgroup of mild asthmatics receiving no regular inhaled medication. In moderate
      asthmatic children, the duration of supplementary beta2-agonist use was strongly
      associated with air pollution. The general pattern of our results provides
      evidence of the effect of the low levels of air pollution encountered in Western
      Europe on symptoms and lung function in childhood asthma.

PMID- 9596122
TI  - Asthma severity and susceptibility to air pollution.
AB  - Exacerbations of asthma have been associated with exposure to ozone or particles
      with a 50% cut-off aerodynamic diameter of 10 microm (PM10). We postulated in
      this study that the association of summertime air pollution (i.e. ozone and PM10)
      with acute respiratory symptoms, medication use and peak expiratory flow differs
      among patients grouped according to asthma severity. During the summer of 1995,
      effects of ambient air pollution on these parameters were studied in a panel of
      60 nonsmoking patients with intermittent to severe persistent asthma. These
      patients were recruited from our Pulmonary Out-patient Clinic. Subgroup analysis
      was performed on the degree of hyperresponsiveness and lung steroid use before
      the start of the study, as indictors for the severity of asthma. Associations of
      the parameters studied with ozone, PM10, nitrogen dioxide (NO2), sulphur dioxide
      (SO2) and black smoke were evaluated using time series analysis. Several episodes
      with increased summertime air pollution occurred during the 96 day study period.
      Eight hour average ozone concentrations exceeded the World Health Organization
      (WHO) Air Quality Guidelines (120 microg x m(-3)) on 16 occasions. Daily mean
      levels of PM10 were moderately elevated (range 16-98 microg x m(-3)). Levels of
      the other measured pollutants were low. There was a consistent, positive
      association of the prevalence of shortness of breath (maximal relative risk
      (RRmax) 1.18) with ozone, PM10, black smoke and NO2. In addition, bronchodilator
      use was associated with both ozone and PM10 levels (RRmax 1.16). Stratification
      by airway hyperresponsiveness and steroid use did not affect the magnitude of the
      observed associations. No associations with peak expiratory flow measurements
      were found. We conclude that the severity of asthma is not an indicator for the
      sensitivity to air pollution.

PMID- 9596123
TI  - Acute asthma epidemics, weather and pollen in England, 1987-1994.
AB  - Recent epidemics of acute asthma have caused speculation that, if their causes
      were known, early warnings might be feasible. In particular, some epidemics
      seemed to be associated with thunderstorms. We wondered what risk factors
      predicting epidemics could be identified. Daily asthma admissions counts during
      1987-1994, for two age groups (0-14 yrs and > or = 15 yrs), were measured using
      the Hospital Episodes System (HES). Epidemics were defined as combinations of
      date, age group and English Regional Health Authority (RHA) with exceptionally
      high asthma admission counts compared to the predictions of a log-linear
      autoregression model. They were compared with control days 1 week before and
      afterwards, regarding seven meteorological variables and 5 day average pollen
      counts for four species. Fifty six asthma epidemics were identified. The mean
      density of sferics (lightning flashes), temperature and rainfall on epidemic days
      were greater than those on control days. High sferics densities were
      overrepresented in epidemics. Simultaneously high sferics and grass pollen
      further increased the probability of an epidemic, but only to 15% (95% confidence
      interval 2-45%). Two thirds of epidemics were not preceded by thunderstorms.
      Thunderstorms and high grass pollen levels precede asthma epidemics more often
      than expected by chance. However, most epidemics are not associated with
      thunderstorms or unusual weather conditions, and most thunderstorms, even
      following high grass pollen levels, do not precede epidemics. An early warning
      system based on the indicators examined here would, therefore, detect few
      epidemics and generate an unacceptably high rate of false alarms.

PMID- 9596124
TI  - Increased sensitivity of the cough reflex in progressive systemic sclerosis
      patients with interstitial lung disease.
AB  - Cough is a common presenting symptom of interstitial lung disease (ILD). The aim
      of this study was to examine the cough reflex in patients with progressive
      systemic sclerosis (PSS), with and without associated ILD. The cough reflex to
      inhalation of chloride deficient solutions and capsaicin was determined in
      patients with PSS with associated ILD (n=12), compared to patients with PSS
      without ILD (n=12). In addition, patients with a chronic dry cough (n=12) and
      healthy subjects (n=10) without cough were studied. Cough responses to inhalation
      of isotonic solutions containing 150, 75, 37.5 and 0 mM Cl- ions and of capsaicin
      (0.9-500 mM) were measured. PSS patients with ILD reported a significantly higher
      cough score than PSS patients without ILD (p<0.03). ILD patients coughed more
      than those without ILD to Cl- of 37.5 and 0 mM (19.1+/-5.0 vs 6.2+/-1.9 coughs x
      min(-1) (p<0.03), and 29.2+/-5.0 vs 14.1/-4.1 coughs x min(-1) (p<0.04),
      respectively). The log concentration of capsaicin causing two or five coughs was
      lower in PSS with ILD compared to PSS without ILD (0.74+/-0.15 mM vs 2.12+/-0.26
      mM; p<0.002). Patients with chronic dry cough had a similar degree of response to
      low-chloride and capsaicin solutions as patients with PSS and ILD, whilst healthy
      controls had a similar degrees of response to PSS patients. There is an increased
      cough reflex in patients with interstitial lung disease, which may represent
      sensitization of airway sensory nerves. This may be the basis for the chronic dry
      cough in patients with interstitial lung disease.

PMID- 9596125
TI  - Predictive value of response to treatment of T-lymphocyte subpopulations in
      idiopathic pulmonary fibrosis.
AB  - T-cell types are important in maintaining immune homeostasis in the lung and
      their imbalance may be associated with several diseases. We examined the
      relationship between bronchoalveolar lavage (BAL) T-cell subset profiles and the
      clinical course of 46 patients with idiopathic pulmonary fibrosis (IPF). A flow
      cytometry cell sorter (FACS) was used to analyse the T-cell subsets. Pulmonary
      function tests (PFT) were performed at baseline and 6-12 months later. Patients
      were divided into two groups according to their CD4/CD8 ratio: CD4/CD8 >1 (group
      1, n=21); and CD4/CD8 <1 (group 2, n=25). A lower percentage of lymphocytes, a
      higher percentage of CD8/S6F1 cells (cytotoxic T-lymphocytes) and a higher
      percentage of neutrophils were found in the BAL in group 2 compared to group 1
      (11+/-7.5% versus 19+/-13.2%; p=0.024 and 29.8+/-17.6% versus 13.3+/-6.9%;
      p=0.068, respectively for lymphocytes and cytotoxic T-lymphocytes; and 8+/-11%
      versus 29+/-27%; p=0.003 for neutrophils). Inversely, in the peripheral blood,
      the distribution of CD8/S6F1 cells was lower in group 1 than in group 2 (8.3+/
      6.9% versus 33.4+/-16.5%; p=0.0048). The patients were followed over a period of
      1 yr in order to test whether those findings could determine efficacy of therapy.
      The baseline transfer factor of the lung for carbon monoxide (TL,CO) capacity in
      group 1 and group 2 was 59+/-22% and 51+/-21%, respectively (p=0.29), but only in
      group 1 was the TL,CO capacity improved significantly in response to steroids
      treatment after 6-12 months. IPF patients with a higher percentage of
      lymphocytes, a lower percentage of neutrophils, CD4/CD8 >1 and a low percentage
      of CD8/S6F1 may have a more benign course of disease. These parameters may
      identify an early stage of reversible disease responsive to therapy. We conclude
      that these measurements may be a useful tool in monitoring response to treatment
      in patients with idiopathic pulmonary fibrosis.

PMID- 9596126
TI  - Blood gas measurement during exercise: a comparative study between arterialized
      earlobe sampling and direct arterial puncture in adults.
AB  - Sampling arterialized earlobe blood is thought to be easier and less painful than
      direct arterial puncture, and to allow measurement of blood gas values during
      exercise without the need to insert an arterial cannula. However, arterialized
      earlobe oxygen tension (PO2) often underestimates arterial PO2 at rest, and is
      not fully validated during exercise. We have therefore conducted a prospective
      study to compare values of PO2 and carbon dioxide tension (PCO2) and the
      discomfort experienced by adult subjects undergoing the two methods of blood
      sampling during exercise. Seventy consecutive adult patients were studied. Blood
      samples were drawn simultaneously from the radial artery and arterialized earlobe
      of each patient during the last minute of an 8 min exercise. Values of PO2 and
      PCO2 were measured by means of blood gas electrodes. The correlation coefficients
      between the two samples were 0.92 for PO2 and 0.91 for PCO2. However, the bias
      and the limits of agreement between the two methods were wide for PO2 (mean+/-2SD
      of the differences between the two methods: 0.63+/-1.50 kPa (4.7+/-11.2 mmHg)).
      The bias and the limits of agreement were smaller for PCO2. Patients felt that
      the earlobe method was not associated with less discomfort than radial artery
      puncture. We conclude that arterialized earlobe blood oxygen tension is not a
      good substitute for arterial oxygen tension during exercise, and should not be
      used to assess arterial oxygen tension in adults during exercise.

PMID- 9596127
TI  - Accuracy of a pulse oximeter in the measurement of the oxyhaemoglobin saturation.
AB  - The aim of the present study was to evaluate the accuracy, in comparison with a
      reference method, of the Nellcor N-20P pulse oximeter in the assessment of
      oxyhaemoglobin saturation (Sa,O2). Sa,O2 was monitored at rest by the Nellcor N
      20P pulse oximeter in 100 subjects (82 males, mean age 68+/-12 yrs) consecutively
      enroled. At the same time, an arterial blood sample was collected for the
      measurement of Sa,O2, carboxyhaemoglobin, and methaemoglobin by an IL-282 Co
      oximeter. A significant difference was found between Sa,O2 values measured with
      the two methods (t=11.78, p<0.05), but the two series of measurements were
      significantly correlated (r=0.97). Both the level and the limits of agreement
      between the two methods were satisfactory when the more appropriate Bland and
      Altman method was applied. Nevertheless, a lack of accuracy of the pulse oximeter
      was found, but only for Sa,O2 values <82% and >94%, as demonstrated by the Youden
      index. In conclusion, these data show that Nellcor N-20P is sufficiently reliable
      for the assessment and monitoring of oxyhaemoglobin saturation. The lack of
      accuracy does not seem clinically relevant since it is appreciable only for
      values at the extremes of the oxyhaemoglobin saturation range.

PMID- 9596128
TI  - Nasal airflow resistance measurement: forced oscillation technique versus
      posterior rhinomanometry.
AB  - This study was designed to determine whether nasal airflow resistance (Rn) which
      is nonlinear during tidal breathing, can be assessed by the forced oscillation
      (FO) technique. Rn values obtained by the FO technique and extrapolated to 0 Hz
      (Rn,FO) were compared to those assessed by posterior rhinomanometry at maximal
      tidal inspiratory flow (Rn,m), at a 0.5 L x s(-1) flow (Rn,F), and at a 1 hPa
      transnasal pressure (Rn,P). All Rn estimates were derived from the same
      inspiratory and expiratory nasal flow and transnasal pressure signals obtained
      during tidal nasal breathing whilst a forced flow was applied at the nose via a
      rigid nasal mask in 23 healthy volunteers, of whom 14 had additional measurements
      after vasoconstrictor treatment. In the basal state, no significant difference,
      and significant correlations (p<0.0001) were found between Rn,FO and the other Rn
      estimates. Only the regression line of Rn,FO versus Rn,m was not significantly
      different from the identity line. After nasal decongestion, Rn,P became
      significantly higher than the other Rn estimates (p<0.005). The regression line
      of Rn,FO versus Rn,m remained nonsignificantly different from the identity line.
      Similar results were observed regarding the percentage values of the different Rn
      estimates after decongestant treatment. This study shows that, despite its
      nonlinearity, Rn can be assessed by the FO technique, and that Rn,FO and Rn,m
      could be indifferently used as physiological indices of nasal patency. As the FO
      technique is more difficult to implement than the conventional rhinomanometry,
      its interest in rhinology appears not to be obvious.

PMID- 9596129
TI  - Quantification of Clara cell protein in rat and mouse biological fluids using a
      sensitive immunoassay.
AB  - Clara cell protein is a 16-17 kDa protein (CC16) secreted by Clara cells in the
      bronchiolar lining fluid of the lung. In order to investigate the potential of
      this protein as a pulmonary marker in animals, CC16 was isolated from rat
      bronchoalveolar lavage fluid (BALF) and a sensitive latex immunoassay applicable
      to both rat and mouse CC16 was developed. The pattern of CC16 concentrations in
      rat biological fluids determined by the immunoassay was consistent with the
      hypothesis of a passive diffusion of the protein across the bronchoalveolar/blood
      barriers showing a difference of more than 5,000 fold between the concentration
      in the epithelial lining fluid (mean, 140 mg x L(-1)) and that in serum (20
      microg x L(-1)) or urine (3 microg x L(-1)). In BALF, the CC16 concentration
      averaged 5,500 microg x L(-1) and was of the same magnitude as that determined on
      lung and trachea homogenates. CC16 was also detectable in amniotic fluid with a
      mean value of 800 microg x L(-1) before delivery. Damage of Clara cells produced
      by methylcyclopentadienyl manganese tricarbonyl resulted in a significant
      decrease of CC16 in BALF but did not affect the serum levels of the protein. The
      nephrotoxicant sodium chromate by contrast had no influence on the CC16 content
      of BALF but markedly increased CC16 levels in both serum and urine as a result of
      impaired glomerular filtration and tubular reabsorption, respectively. In
      conclusion, mouse or rat Clara cell protein of 16-17 kDa can easily be
      quantified, not only in bronchoalveolar lavage fluid, but also in extrapulmonary
      fluids such as serum or urine. Thus, in rodents, Clara cell protein of 16-17 kDa
      follows the same metabolic pathway as in humans, diffusing from the respiratory
      tract into serum where it is eliminated by the kidneys. This serum Clara cell
      protein of 16-17 kDa may be useful as a peripheral marker of events taking place
      in the respiratory tract.

PMID- 9596130
TI  - Eosinophil cationic protein in sputum is dependent on temperature and time.
AB  - Eosinophil cationic protein (ECP) in sputum may be used to estimate the severity
      of bronchial inflammation and obstruction in asthmatics as well as to monitor
      asthma drug therapy. For this purpose, standardized processing of sputum is
      important. The aim of our study was to determine whether time and temperature
      influence the ECP concentration in the sputum of asthmatics. The samples of
      induced sputum obtained from 12 patients with stable asthma were homogenized
      using ultrasonification, and centrifuged. Supernatants were evenly divided and
      stored for 1, 6, 24 or 72 h at either 4 or 25 degrees C, then frozen at -80
      degrees C. The ECP concentrations were determined using fluoroimmunoassay and
      compared with the immediately frozen samples. After storing at 4 degrees C, the
      ECP levels at the four time points were 101.2, 96.0, 98.2 and 90.6% of the
      initial concentration, respectively. When sputum specimens were stored at 25
      degrees C, ECP levels decreased to 96.1, 94.4, 90.7 and 87.7%, respectively. The
      influence of time on ECP concentrations in sputa was statistically significant
      (p=0.02). A significant temperature effect was found when comparing the specimens
      stored at 4 degrees C with those at 25 degrees C (p=0.03). Looking at individual
      time points, a significant decrease in ECP concentration was only seen at 25
      degrees C after 24 and 72 h. We conclude that eosinophilic cationic protein in
      the sputum of asthmatics decreases in a time- and temperature-dependent process.
      If sputa cannot be processed after obtaining the specimens, they should be stored
      in a refrigerator at 4 degrees C, until eosinophilic cationic protein is
      measured.

PMID- 9596131
TI  - Lung transplantation for pulmonary sarcoidosis.
AB  - Patients with end-stage sarcoidosis have now undergone lung transplantation
      successfully with good short-term and intermediate-term results. Lung
      transplantation for sarcoidosis requires several considerations unique to this
      disease. Selection of pulmonary sarcoidosis patients for transplantation requires
      that medical therapy has been exhausted. This may involve the use of
      corticosteriods and alternative medications. Causes of pulmonary dysfunction
      other than pulmonary sarcoidosis, such as bronchiectasis and myocardial
      sarcoidosis, must be excluded before candidates are considered for
      transplantation. The extent and severity of extrapulmonary disease must also be
      assessed and may preclude lung transplantation. The presence of mycetomas is
      considered a relative contra-indication by some transplant centres and an
      absolute contra-indication by others. Relatively few patients with pulmonary
      sarcoidosis have undergone transplantation and, therefore, there are few data on
      outcome. Sarcoidosis frequently recurs in the allograft, but rarely causes
      symptoms or pulmonary dysfunction. More severe acute rejection episodes may occur
      in sarcoidosis transplant recipients, although at present there is no evidence of
      an increased risk of obliterative bronchiolitis or increased mortality.

PMID- 9596132
TI  - Reactive oxygen species in acute lung injury.
AB  - The acute respiratory distress syndrome (ARDS) in adults is associated with a
      wide variety of precipitating factors, often not directly involving the lung, and
      has an associated mortality of 50-80%. ARDS is almost invariably associated with
      sepsis, either as an initiating factor or as a secondary complication, which
      increases the expression of a number of cytokines impacting upon several cellular
      systems. Specifically, activation of neutrophils sequestered in the pulmonary
      circulation by this process, causes the release of free radicals and reactive
      oxygen species (ROS), increasingly regarded as key substances modulating the
      endothelial dysfunction and disruption responsible for the principal clinical
      manifestations of the syndrome. Here we discuss briefly the pathophysiology of
      ARDS and its impact upon pulmonary vascular control; the biological origins of
      free radicals and other ROS involved, the mechanisms of their damaging effects,
      their contribution to the modification of pulmonary vascular control mechanisms
      in lung injury and possible therapeutic perspectives.

PMID- 9596133
TI  - Calcium ATPase and respiratory muscle function.
AB  - The sarcoplasmic reticulum (SR) of striated muscle is a highly specialized
      intracellular membrane system that plays a key role in the contraction-relaxation
      cycle of muscle. Its primary function is the regulation of cytoplasmic Ca2+
      concentration. A key element in this regulation is the Sarco(endo)plasmic
      reticulum Ca2+-adenosine triphosphatase (SERCA), which by sequestering Ca2+ into
      the SR, induces and maintains relaxation. It has been extensively studied with
      respect to structure and mechanism of action, and more recently to gene
      expression. Three separate genes encode five SERCA isoforms, two of which, SERCA
      1 and SERCA 2, are expressed in skeletal muscle. In the first part of this review
      we focus on the general properties of the Ca2+ pump (structure and function and
      regulation of activity). In the second part we describe variations in SERCA
      expression in various physiological and pathological situations. These have
      essentially been studied in the heart and skeletal muscles, with data in
      respiratory muscles being very limited.

PMID- 9596134
TI  - Isolated pulmonary arteries involvement in a patient with Takayasu's arteritis.
AB  - Pulmonary arteries involvement is well described in Takayasu's arteritis (TA), a
      condition which is mainly associated with involvement of the systemic arteries.
      We report a case of TA with documented isolated pulmonary arteries involvement.
      Symptoms were quite similar to those encountered in chronic thromboembolic
      disease. A pulmonary angiogram showed bilateral stenosis and occlusion of
      pulmonary arteries. Diagnosis of TA was suspected, and as such a complete
      aortogram was made but proved to be normal. Massive haemoptysis suddenly
      occurred, which resulted in death. Autopsy disclosed characteristic pathological
      lesions of TA in pulmonary arteries and confirmed the lack of involvement of the
      aorta and its branches. The frequency of such a clinical form could be
      underestimated, given the difficulties of diagnosis and features similar to those
      of chronic thromboembolic disease.

PMID- 9596135
TI  - Accelerated obstructive pulmonary disease in HIV infected patients with
      bronchiectasis.
AB  - Human immunodeficiency virus (HIV) infection has been associated with a wide
      spectrum of pulmonary disease. We report three HIV-seropositive patients with
      rapidly worsening airway obstruction associated with bronchiectasis. All subjects
      (age range 33-39 yrs) were cigarette smokers. Two had previously used intravenous
      drugs. The CD4 lymphocyte count ranged 40-250 cells x mm(-3). All individuals had
      complained of increasing dyspnoea for 3-6 months. Within 1 yr, they all developed
      severe airway obstruction with a decrease in both forced expiratory volume in one
      second (FEV1) and ratio of FEV1 to forced vital capacity (FEV1/FVC) to less than
      60% of predicted value, and a decrease in mean forced expiratory flow at 25-75%
      of the forced vital capacity (FEF25-75) to less than 35% of predicted value.
      Computed tomography of the chest disclosed bilateral dilated and thickened
      bronchi. No classical causes of genetic or acquired bronchiectasis were
      identified in our patients. Recurrent bacterial bronchitis occurred in the follow
      up period of the three patients. In conclusion, unusually rapid airway
      obstruction associated with bronchiectasis should be added to the wide spectrum
      of respiratory complications of human immunodeficiency virus infection.

PMID- 9596136
TI  - Recurrent varicella pneumonia complicating an endogenous reactivation of
      chickenpox in an HIV-infected adult patient.
AB  - We report the case of an adult patient with acquired immune deficiency syndrome
      (AIDS) presenting with acute dyspnoea and cutaneous disseminated lesions
      suggestive of an atypical varicella. The chest radiograph and the computed
      tomography (CT)-scan revealed a miliary pneumonia. On a previous serum sample
      varicella-zoster (VZV)-specific serum immunoglobulin (Ig)G titre was 1/200. A
      high dose acyclovir treatment was effective, but recurrences occurred twice when
      the treatment was discontinued. During the first recurrence the polymerase chain
      reaction (PCR) detected the presence of VZV in the bronchoalveolar lavage (BAL)
      sample. These findings confirmed the diagnosis of secondary varicella with
      pulmonary involvement. Secondary varicella pneumonia has not been reported in a
      human immunodeficiency virus (HIV)-infected adult until now. The use of PCR on a
      BAL sample was very useful in this case because viral culture remained negative.
      Recurrences of the varicella pneumonia suggested that a maintenance treatment was
      required in this deeply immunocompromised patient.

PMID- 9596137
TI  - Pyothorax-associated lymphoma: relationship with Epstein-Barr virus, human herpes
      virus-8 and body cavity-based high grade lymphomas.
AB  - Pyothorax-associated lymphoma (PAL) is a newly-described entity developing
      several decades after artificial pneumothorax treatment for pulmonary or pleural
      tuberculosis. It is known to be associated with Epstein-Barr virus (EBV) with
      constant expression of the two latent membrane proteins: latent membrane protein
      (LMP)-1 and EBV-associated nuclear antigen (EBNA)-2. We are reporting three new
      cases of PAL. All of the tumours were of B-cell lineage and classified as large
      cell diffuse lymphomas according to the International Working Formulation for the
      Classification of Lymphomas. The EBV genome was detected in two of the cases with
      LMP-1 and EBNA-2 expression. No EBV could be detected in the third case
      suggesting that different mechanisms may be involved in the pathogenesis of the
      disease. Body cavity-based high grade lymphomas (BCBL) represent a new disease,
      developing mainly in human immunodeficiency virus (HIV) infected patients: the
      tumoural cells often contain both human herpes virus (HHV)-8 (or Kaposi's sarcoma
      herpes virus) and EBV genomes, suggesting that these viruses might co-operate in
      the pathogenesis of the disease. The pleural location and the association of EBV
      have led to speculation that PAL could also be related to HHV-8 infection.
      However, no HHV-8 genome could be detected in any of the 14 tested cases already
      reported in the literature nor in the two cases we studied (one EBV-positive and
      one EBV-negative), suggesting that PAL and BCBL are two different entities.

PMID- 9596138
TI  - A preoperative consultation for a patient with chronic cough and wheeze.

PMID- 9596139
TI  - Reproducibility of lung volume measurements.
AB  - Test reproducibility is an important consideration when interpreting results and
      should be set as a goal during data collection. Reproducibility criteria may need
      to be different for different subject groups and are instrument and procedure
      dependent. Ideally, the within-subject variability for each lung volume and
      measurement technique used should be established for each laboratory. These
      values also need to be established for each different subject group (age and
      disease). At a minimum, test reproducibility should be monitored and controlled
      and each laboratory should define their between-day reproducibility of
      measurements on at least one "reference" subject from ongoing periodic (e.g.,
      weekly or monthly) measurements as part of their laboratory's quality control
      programme. For plethysmographic measurements functional residual capacity
      (FRC)pleth multiple determinations and a corresponding test reproducibility
      criteria is probably justified.

PMID- 9596140
TI  - Reference values for maximal work capacity in healthy children.

PMID- 9596141
TI  - Women's respiratory vulnerability to tobacco smoking.

PMID- 9596142
TI  - An animal model for simultaneous pharmacokinetic/pharmacodynamic investigations:
      application to cocaine.
AB  - An animal model suitable for pharmacokinetic/pharmacodynamic investigations is
      described. This model allows drug administration via different routes, serial
      blood sampling, serial brain ECF sampling, and monitoring the cardiovascular
      functions without touching the animal. This rat model was utilized to study the
      relationship between cocaine pharmacokinetics and the neurochemical and
      cardiovascular responses to cocaine administration via different routes. The
      pharmacokinetic results showed that the average cocaine bioavailability after
      i.p. administration was 71% and after oral administration was only 19.2%. Cocaine
      was rapidly distributed into the brain, and the brain ECF/plasma distribution
      ratio measured as the ratio of the brain ECF AUC to the plasma AUC was 2.02 +/-
      0.59. The relationship between cocaine brain ECF concentration and the change in
      dopamine brain ECF concentration was described by the sigmoid Emax
      pharmacodynamic model. When the relationship between cocaine plasma concentration
      and the change in the cardiovascular functions was examined, hysteresis loops
      were observed. These hysteresis loops may suggest the existence of an effect
      compartment for the cardiovascular effects of cocaine or that cocaine metabolites
      are contributing to cocaine cardiovascular effects. These results indicate that
      the described animal model is useful in simultaneous
      pharmacokinetic/pharmacodynamic investigations specifically for studies that
      involve centrally acting drugs.

PMID- 9596143
TI  - Improved methods for transplanting split-heart neonatal cardiac grafts into the
      ear pinna of mice and rats.
AB  - The rodent heterotopic ear-heart transplant method is a useful alternative to the
      more technically demanding vascularized graft technique. We modified the
      procedure to improve efficiency and used it in mice and rats to determine the
      survival times of both isologous and allogeneic grafts and compare reference
      immunosuppressants. Bisected rat and mouse cardiac (split-heart) isografts were
      uniformly viable up to 4 weeks postimplant; however, by 24 weeks only 90% of
      Lewis rat or C3H mouse split-heart isografts retained electrocardiographic
      activity, regressing to 81% by 60 weeks for the Lewis rat and to less than 50%
      for the C3H mouse by 43 weeks post-implant. The potency of tacrolimus, sirolimus,
      and cyclosporine for prevention of allograft rejection was comparable whether
      using split-hearts or whole hearts in the Balb/C to C3H mouse model. The
      maximally effective doses at 2 weeks postimplant for intraperitoneally
      administered tacrolimus, sirolimus, cyclosporine, and oral leflunomide with Brown
      Norway (BN) to Lewis rat ear-split-heart allografts (0.3, 0.1, 3.0, 10,
      mg/kg/day, respectively) agreed extremely well with published data for the rat
      primary vascularized heterotopic heart model. This reproducible and efficient
      transplantation model was improved by using split-hearts to double available
      donor tissue, a gonadotropin-enhanced breeding strategy that enables routine use
      of low-fecundity inbred rats as donors, implantation devices that speed and
      simplify the procedure, and defined electrocardiographic evaluation criteria to
      maximize sensitivity and provide an objective endpoint for defining rejection.

PMID- 9596144
TI  - Pharmacokinetic-pharmacodynamic modelling of the analgesic effect of alfentanil
      in the rat using tooth pulp evoked potentials.
AB  - The purpose of the present study was to develop an animal model for the
      investigation of the concentration-effect relationship of alfentanil using tooth
      pulp evoked potentials (TPEP). Six chronically instrumented, freely moving rats
      received a computer-controlled intravenous infusion of alfentanil resulting in
      seven pseudo-steady-state blood concentration levels, each maintained for 30 min.
      At each concentration level, the tooth pulp of the rat upper incisor was
      electrically stimulated in a time-randomized order with different current
      intensities (400-800 microA, 1 msec duration) and the electroencephalogram (EEG)
      was recorded concomitantly. Arterial blood samples were collected serially and
      assayed for alfentanil using RIA. Repetitive evoked EEG responses were averaged
      per stimulus intensity and per session. The decrease of the area under the
      negative peak 15 msec after stimulation (% of preadministration value) was used
      as pharmacological endpoint. The concentration-TPEP effect of alfentanil was
      investigated by nonlinear mixed effect modeling (NONMEM). When the observed TPEP
      effect was plotted versus the alfentanil blood concentration no hysteresis or
      proteresis was observed, and the two could directly be related to each other on
      the basis of the sigmoidal Emax pharmacodynamic model. The (population)
      pharmacodynamic estimates were (+/-S.E.): Emax = 108 +/- 10%, EC50 = 24 +/- 17
      ng/ml, Hill factor = 0.81 +/- 0.37. A large interindividual variability for EC50
      (omegaEC50) of 164 +/- 107% was observed. The residual variability was 14 +/-
      10%. It is concluded that the TPEP is a useful tool for the systematic
      investigation of the concentration-analgesic effect relationship of centrally
      acting analgesics in the freely moving rat.

PMID- 9596145
TI  - Quantitative whole-body autoradiography in pregnant rabbits to determine fetal
      exposure of potential teratogenic compounds.
AB  - Whole-body autoradiography (WBA) allows the determination of sites of
      accumulation and differential distribution of radiolabeled compounds within
      organs. WBA is routinely conducted in pregnant rats to evaluate placental
      transfer and fetal distribution of potential developmental toxins. This technique
      has recently been adapted to evaluate tissue distribution in the pregnant rabbit,
      which may be a more appropriate model for some pharmaceutical candidates. A
      preliminary WBA study was conducted on New Zealand white (NZW) rabbits at
      gestation day 18, 1 h following a single oral dose of 14C-glucose. The purpose of
      this study was to validate the use of WBA techniques in assessing the placental
      transfer of compounds in pregnant rabbits. Antiviral compound LY217896 sodium
      demonstrated developmental toxicity in the pregnant NZW rabbit following multiple
      oral doses of 10 mg/kg on gestation days 6 through 18. WBA techniques were used
      to determine the distribution of radiocarbon 30 minutes following a single oral
      10-mg/kg dose of 14C-LY217896 sodium in pregnant NZW rabbits on gestation day 18.

PMID- 9596146
TI  - Development of an optimal method for the dual perfusion of the isolated rat
      liver.
AB  - The liver receives two blood supplies, the portal vein (PV) and hepatic artery
      (HA). The isolated perfused rat liver preparation (IPRL) is widely used to
      examine physiological factors affecting the hepatic disposition of compounds, but
      usually it is perfused via the PV only. In the development of a more
      physiological dual perfused system, we examined three surgical procedures for HA
      perfusion--cannulation through the gastroduodenal artery, the aorta, and the
      celiac artery--using 14C-urea as the reference marker. Similar efflux profiles
      for 14C-urea were obtained for all three procedures, with a clear difference
      between HA and PV administration; however, cannulation of blood vessels and
      isolation of the HA supply were the most reliable with the celiac artery
      cannulation, making it the preferred procedure.

PMID- 9596147
TI  - Sample dilution: a methodological pitfall in the measurement of tissue but not
      serum ace-activity.
AB  - Many tissue ACE-assays suffer from underestimation of the ACE-activity at low
      sample dilutions. However, measurement of ACE-activity as the amount of hippuric
      acid produced by cleavage of the commonly used substrate hippuryl-histidyl
      leucine might circumvent this problem. In this study, we investigated whether
      sample dilution affects the measurement of ACE-activity in rat tissue and serum.
      We found that serum ACE-activity was not affected by sample dilution. In
      homogenates of aorta, kidney, left ventricle, and lung, however, ACE-activity
      increased 1.6-2.8 times with increasing sample dilution until, ultimately, a
      plateau was reached at dilution factor 100, 50, 20, and 100, respectively. In
      addition, tissue homogenates inhibited the activity of exogenous ACE, whereas
      serum did not. These data suggest that the dilution effect probably results from
      interactions of inhibitory substances from the homogenates with ACE. The
      implications of these findings are that tissue ACE-activity measurements by any
      assay should be performed using sample dilution at the plateau. In many studies
      in the literature, specifications of sample dilution are lacking. Our findings
      demonstrate that caution is warranted in the interpretation of these studies.

PMID- 9596148
TI  - Chlamydia pneumoniae and occlusive vascular disease: identification and
      characterization.
AB  - Chlamydia pneumoniae, a respiratory pathogen, has been associated with occlusive
      vascular disease, including atherosclerosis and intimal hyperplasia, through
      seroepidemiologic studies. Furthermore, using immunohistochemistry (IHC),
      polymerase chain reaction (PCR), transmission electron microscopy (TEM), and in
      situ hybridization, this association has been reconfirmed by detecting this
      organism in atherosclerotic vascular tissue. This review summarizes and
      critically analyzes these findings and also discusses various mechanisms of how
      Chlamydia pneumoniae could be involved in the pathogenesis of occlusive vascular
      disease. Although more studies are needed to reproduce these results and,
      possibly, uncover a mechanism, the current literature fails to include detailed
      methodologies for studying Chlamydia pneumoniae. Therefore, to provide a general
      standard, we have also outlined specific protocols for IHC, PCR, and TEM. These
      protocols incorporate essential components from various studies and are presented
      in a concise and easily adaptable format.

PMID- 9596149
TI  - Mid-arm sentinel lymph nodes showing surprising drainage from a malignant
      melanoma in the forearm.
AB  - A 51-year-old man with a malignant melanoma in his left forearm was studied to
      detect the sentinel lymph node and to assess the possibility of micrometastases
      in regional lymph nodes. Lymphoscintigraphy demonstrated two sentinel lymph nodes
      in the midarm. Two other nodes in the same location as well as in the left axilla
      were also observed. The exact location of the sentinel lymph nodes was identified
      with a gamma-ray detector. At the time of surgery, blue dye was injected around
      the primary lesion and the two sentinel lymph nodes on the inner side of the left
      arm were resected. Both lymph nodes were pigmented black. The histopathologic
      study demonstrated metastases from malignant melanoma in both nodes. This case
      reflects the main role of lymphoscintigraphy in identifying draining lymph nodes
      in unusual locations as observed in this patient.

PMID- 9596150
TI  - Brain SPECT imaging using three different tracers in subacute cerebral
      infarction.
AB  - Two patients with subacute cerebral infarction underwent benzodiazepine receptor
      imaging using I-123-iomazenil and cerebral perfusion imaging with Tc-99m HMPAO
      and Tc-99m ECD. Iomazenil early images resembled HMPAO images, which demonstrated
      increased uptake in a part of the infarcted site. Iomazenil delayed images and
      ECD images showed reduced accumulation in the same area. Crossed cerebellar
      diaschisis was observed in HMPAO, ECD, and iomazenil early images, but it was not
      remarkable in iomazenil delayed images. These cases suggest that sequential
      iomazenil images visualized increased uptake with relatively impaired viability
      in the infarcted site and hypoperfusion with preserved viability in the
      contralateral cerebellar hemisphere, which could not be recognized without using
      both HMPAO and ECD in the subacute phase of cerebral infarction.

PMID- 9596151
TI  - The clinical utility of quantitative cholescintigraphy: the significance of
      gallbladder dysfunction.
AB  - PURPOSE: Cholelithiasis is a common disorder occurring in over 20 million people
      in the United States and resulting in approximately 600,000 cholecystectomies
      annually. Although over 95% of biliary tract disease is caused by gallstones, the
      vast majority (>80%) of cholelithiasis cases are asymptomatic. The purpose of
      this study is to evaluate the utility of quantitative cholescintigraphy in
      detecting symptomatic biliary tract disease and predicting clinical relief after
      cholecystectomy. MATERIALS AND METHODS: Fifty-two patients with clinical symptoms
      of chronic cholecystitis were evaluated by cholescintigraphy with a gallbladder
      ejection fraction calculated after the intravenous administration of
      cholecystokinin. A gallbladder ejection fraction of > or =35% was considered a
      normal physiologic response. Forty-one of the patients subsequently underwent
      cholecystectomy, whereas the remaining 11 subjects were diagnosed and treated for
      non-biliary disorders that did not require cholecystectomies. After clinical
      follow-up including histopathological gallbladder findings, all subjects' final
      diagnoses were established and correlated with their quantitative cholescintigram
      study. RESULTS: Twenty-six of twenty-eight patients who had an abnormal
      quantitative cholescintigram demonstrated evidence of chronic cholecystitis by
      histopathologic criteria after cholecystectomy. Furthermore, 27 of these 28
      patients (96%) experienced complete relief of their clinical symptoms after
      surgery. CONCLUSION: Functional cholescintigraphy is a safe, accurate, and useful
      test for detecting symptomatic gallbladder disease, and appears reliable in
      predicting symptomatic relief after cholecystectomy.

PMID- 9596152
TI  - Tc-99m sestamibi imaging in the diagnostic assessment of patients with lymphomas:
      comparison with clinical and radiological evaluation.
AB  - Tc-99m MIBI imaging has been used in nuclear oncology, but its role in detecting
      lymphomas has not been widely investigated. In this study, 31 patients with
      lymphomas (20 non-Hodgkin's and 11 Hodgkin's) underwent Tc-99m MIBI whole-body
      imaging. A total of 74 tumor lesions were detected in 25 patients, while the
      remaining 6 patients were disease-free. The diagnostic accuracy of MIBI imaging
      for lesion detection was 85%. A total of 11 unknown tumor lesions in 3 patients
      were discovered on MIBI scans. Tumor size was significantly (p = 0.01) higher in
      lesions with increased MIBI uptake (3.5 +/- 2.0 cm) compared with those with no
      uptake (1.8 +/- 1.0 cm). No false positive MIBI findings were observed. The
      accuracy of MIBI scintigraphy in patients with Hodgkin's disease was lower (72%)
      compared to that of patients with non-Hodgkin's lymphomas (94%). However, this
      difference was not related to tumor type, but to lesion size. In fact, tumor size
      was significantly (p = 0.02) lower in lesions of patients with Hodgkin's disease
      (2.5 +/- 1.3 cm) compared to those of patients with non-Hodgkin's lymphomas (3.7
      +/- 2.2 cm). MIBI imaging may be useful in patients with lymphomas for detecting
      tumor lesions and, hence, may be considered an alternative to gallium scanning,
      providing better imaging quality. However, the intense Sestamibi activity in the
      lower chest and abdomen as well as tumor size may limit the diagnostic
      sensitivity of this radionuclide technique in patients with lymphomas.

PMID- 9596153
TI  - Double-phase Tc-99m sestamibi scintigraphy in the preoperative location of
      lesions causing hyperparathyroidism.
AB  - Hyperparathyroidism (HPT) is one of the most prevalent endocrine diseases, for
      which the only effective treatment is surgery. The use of imaging techniques in
      the preoperative localization of the hyperfunctioning glands is the subject of
      controversy. The purpose of this paper is to assess the use of double-phase
      scintigraphy with Tc-99m sestamibi in the localization of lesions causing HPT. We
      used scintigraphy to preoperatively examine 41 patients, 31 of whom had primary
      HPT and 10 with secondary HPT. We acquired two anterior view planar images of the
      neck and chest 10 minutes and 3 hours after injection of Tc-99m sestamibi. Final
      diagnosis, determined with biopsy, was adenoma in 26 patients, 24 of whom had a
      positive scintigraphic study (sensitivity 92%), with only two false negative
      results. In the 14 cases of parathyroid hyperplasia, scintigraphy was also
      positive, and 62% (30/48) of the excised glands were identified by Tc-99m
      sestamibi. The radioisotope study was of particular interest in the six patients
      who previously had undergone surgery, since all the studies were positive; in two
      patients, additional diseased glands were located in the neck, and an ectopic
      adenoma was found in the remaining four patients. A fifth ectopic lesion was also
      sestamibi-positive and, in this case, the scintigraphic result was a direct
      indication for mediastinal surgery. There were no false positive results, even in
      patients with multinodular goiter. We conclude that, due to its high sensitivity
      and the ease with which it is performed, double-phase scintigraphy with Tc-99m
      sestamibi is the preferred technique for the preoperative localization of
      diseased glands in patients with HPT, especially in cases of parathyroid adenoma,
      including those with aberrant location. Its use is of particular interest in
      patients who previously have undergone surgery.

PMID- 9596154
TI  - Uptake of In-111 pentetreotide by pleural plaques.
AB  - Somatostatin receptor imaging with In-111 pentetreotide has been validated for
      the diagnosis and staging of chest tumors with neuroendocrine differentiation
      such as bronchial carcinoid and small cell lung cancer. In-111 pentetreotide
      uptake is not specific for neuroendocrine tumors because somatostatin receptors
      are also expressed by white blood cells, leading to the in vivo visualization
      sites of infection sites or active inflammation. Pleural plaques may be due to
      asbestos exposure or tuberculosis. Presented here are three cases of In-111
      pentetreotide uptake in pleural plaques. This uptake by benign lesions may be
      misleading in the diagnostic work-up of patients with lung tumors.

PMID- 9596155
TI  - Usefulness of scintigraphy with Tc-99m phytate for the diagnosis of alcoholic
      foamy degeneration.
AB  - PURPOSE: Alcoholic foamy degeneration (AFD) is a liver disease causing temporary
      hepatocyte dysfunction. The prognosis is usually good, but liver biopsy is needed
      for diagnosis. We report the usefulness of liver-spleen scintigraphy with the
      radiocolloid Tc-99m phytate for the diagnosis of AFD. PATIENTS AND METHODS: We
      used liver scintigraphy with Tc-99m phytate to study three patients with AFD
      diagnosed on the basis of findings from a liver biopsy. RESULTS: Liver-spleen
      scintigraphy showed hepatomegaly and splenomegaly, and bone marrow was visible,
      but radioisotope uptake by the liver was uniform. CONCLUSIONS: This pattern of
      scintigraphic findings is different from that reported for patients with
      alcoholic fatty livers or severe alcoholic hepatitis, and seems to be specific
      for AFD.

PMID- 9596156
TI  - Detection of nasopharyngeal carcinoma with head and neck Tc-99m tetrofosmin SPECT
      imaging.
AB  - Tc-99m tetrofosmin SPECT imaging of the head and neck was performed on 10
      patients with nasopharyngeal carcinoma (NPC) and 10 controls. There was no
      abnormal nasopharyngeal uptake of tetrofosmin in the 10 controls. In the patients
      with NPC, 3/10 (30%) of the cases had no abnormal uptake and 7/10 (70%) had
      increased nasopharyngeal uptake. Considering our preliminary study, we find that
      Tc-99m tetrofosmin SPECT of the head and neck may be helpful in the detection of
      NPC. However, further study with a larger number of patients is needed to
      ascertain the value of Tc-99m tetrofosmin SPECT in such cases.

PMID- 9596158
TI  - Renal accumulation of Tc-99m albumin colloid in a patient with multiple
      cardiovascular events.

PMID- 9596157
TI  - SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury.
AB  - The purpose of this atlas is to present a review of the literature showing the
      advantages of SPECT brain perfusion imaging (BPI) in mild or moderate traumatic
      brain injury (TBI) over other morphologic imaging modalities such as x-ray CT or
      MRI. The authors also present the technical recommendations for SPECT brain
      perfusion currently practiced at their center. For the radiopharmaceutical of
      choice, a comparison between early and delayed images using Tc-99m HMPAO and Tc
      99m ECD showed that Tc-99m HMPAO is more stable in the brain with no washout over
      time. Therefore, the authors feel that Tc-99m HMPAO is preferable to Tc-99m ECD.
      Recommendations regarding standardizing intravenous injection, the acquisition,
      processing parameters, and interpretation of scans using a ten grade color scale,
      and use of the cerebellum as the reference organ are presented. SPECT images of
      228 patients (age range, 11 to 88; mean, 40.8 years) with mild or moderate TBI
      and no significant medical history that interfered with the results of the SPECT
      BP were reviewed. The etiology of the trauma was in the following order of
      frequency: motor vehicle accidents (45%) followed by blow to the head (36%) and a
      fall (19%). Frequency of the symptoms was headache (60.9%), memory problems
      (27.6%), dizziness (26.7%), and sleep disorders (8.7%). Comparison between
      patients imaged early (<3 months) versus those imaged delayed (>3 months) from
      the time of the accident, showed that early imaging detected more lesions (4.2
      abnormal lesions per study compared to 2.7 in those imaged more than 3 months
      after the accident). Of 41 patients who had mild traumatic injury without loss of
      consciousness and had normal CT, 28 studies were abnormal. Focal areas of
      hypoperfusion were seen in 77% (176 patients, 612 lesions) of the group of 228
      patients. The sites of abnormalities were in the following order: basal ganglia
      and thalami, 55.2%, frontal lobes, 23.8%, temporal lobes, 13%, parietal, 3.7%,
      insular and occipital lobes together, 4.6%.

PMID- 9596159
TI  - Radioiodine uptake in rheumatoid arthritis-associated lung disease mimicking
      thyroid cancer metastases.

PMID- 9596160
TI  - False-negative blood pool scan in hepatic angiosarcoma.

PMID- 9596161
TI  - Tc-99m albumin scintigraphy in protein-losing gastroenteropathy caused by gastric
      polyposis.

PMID- 9596162
TI  - Differentiation of cardiac tumor from thrombus by combined MRI and F-18 FDG PET
      imaging.

PMID- 9596163
TI  - The bench press mark revisited.

PMID- 9596164
TI  - Chronic mastoid sinusitis mimicking metastatic disease demonstrated by Tc-99m
      HMDP bone scintigraphy.

PMID- 9596165
TI  - Photon-deficient bone metastases in hepatocellular carcinoma.

PMID- 9596166
TI  - Presacral hematopoietic tissue: correlation of radionuclide and MRI findings.

PMID- 9596167
TI  - Ectopic laryngeal parathyroid adenoma detected by SPECT sestamibi imaging.

PMID- 9596168
TI  - Esophageal scarring causing false-positive uptake on I-131 whole-body imaging.

PMID- 9596169
TI  - Ga-67 inguinal lymph node imaging in patients with sarcoidosis: a third typical
      common pattern.

PMID- 9596170
TI  - Detection of renal cortical defects.

PMID- 9596171
TI  - News from the National Institute on Deafness and Other Communication Disorders.

PMID- 9596172
TI  - Increased numbers of mast cells in human middle ear cholesteatomas: implications
      for treatment.
AB  - HYPOTHESIS: Because many of the biologic phenomena in which mast cells are
      involved also are observed in human cholesteatoma pathology, the authors
      hypothesized that mast cells may play a role in this disease. The first test of
      this hypothesis is to determine whether there are an increased number of mast
      cells associated with cholesteatomas. BACKGROUND: The molecular and cellular
      defects that result in the pathologic features observed in acquired and
      congenital cholesteatomas are unknown. One common feature of cholesteatoma
      pathogenesis is the presence of bacteria and a numerous inflammatory cytokines
      expressed by host inflammatory cells. The interactions between inflammatory cells
      and cholesteatoma epithelium could result in the induction of other aberrant
      biologic features of cholesteatomas. Thus, it is critical to the understanding of
      the pathogenesis of cholesteatomas to define the specific role of each cell type
      involved in this disease. Connective tissue mast cells have a complex retinue of
      functions mediated via the secretion of a variety of cytokines and proteinases,
      and many of the biologic phenomena in which mast cells are involved also are
      observed in cholesteatoma pathology. METHODS: The authors evaluated by
      immunohistochemistry 36 cholesteatomas of all types (e.g., primary and secondary
      acquired, recurrent, and congenital) and 23 specimens of normal tissues (e.g.,
      tympanic membrane, canal wall skin, and postauricular skin) for the expression of
      tryptase, a mast cell-specific protease. RESULTS: Cholesteatomas showed
      approximately threefold to sevenfold increase in the concentration of mast cells
      when compared with that of normal tissues. In addition, 19-34% of the mast cells
      were found within the suprabasal layers of the squamous epithelium of
      cholesteatoma subgroups, a phenomenon observed only in grossly inflamed tympanic
      membrane specimens, but not in other control tissues including minimally inflamed
      tympanic membranes. CONCLUSIONS: The authors conclude from these data that mast
      cells may represent a previously unrecognized host inflammatory cell, which plays
      an important role in the development of one or more traits of cholesteatoma
      pathology.

PMID- 9596173
TI  - Gold prostheses for ossiculoplasty.
AB  - OBJECTIVE: To review the results of ossicular chain reconstruction with partial
      and total ossicular replacement prostheses made of gold. STUDY DESIGN:
      Retrospective case review. SETTING: A tertiary referral center. PATIENTS: Fifty
      nine patients underwent surgery between November 1993 and February 1996 and
      underwent follow-up for at least 12 months. Tympanoplasty was performed because
      of cholesteatoma, chronic otitis media, adhesive otitis media, and trauma.
      INTERVENTION: Tympanoplasty and ossiculoplasty with partial or total replacement
      gold prostheses. MAIN OUTCOME MEASURE: The clinical and hearing results of
      ossiculoplasty. RESULTS: In 62% of the patients in whom partial ossicular
      replacement prostheses were used, the residual air-bone gap could be reduced to <
      or =20 dB. In cases with total ossicular replacement prostheses, the air-bone gap
      could be closed to < or =20 dB in 42%. Extrusion of the prosthesis occurred in 11
      cases (19%) between 7 and 21 months after tympanoplasty. In most extrusion cases
      (55%), this was combined with a significant retraction of the tympanic membrane.
      Primary and staged procedures showed different extrusion rates. CONCLUSIONS:
      Hearing results in the current study are comparable to results described by other
      authors for synthetic middle ear prostheses. Implant rejection was never
      encountered, with the gold implants exhibiting a high biocompatibility.
      Nevertheless, prosthesis extrusion occurred rather often in the course of
      tympanic membrane retraction. Staging the surgery or different shaping of the
      prosthesis may be helpful to prevent prosthesis extrusion.

PMID- 9596174
TI  - Laser stapedotomy minus prosthesis (laser STAMP): a minimally invasive procedure.
AB  - OBJECTIVE: To determine whether hearing can be restored using a laser without a
      prosthesis in patients with minimal otosclerosis. STUDY DESIGN: Retrospective
      case review of 12 patients with minimal otosclerosis who underwent a laser
      stapedotomy without prosthesis (laser STAMP) procedure. SETTING: An
      otology/neurotology tertiary referral center. PATIENTS: Patients were chosen for
      the procedure if there was a blue footplate with minimal otosclerosis confined to
      the fissula antefenestram. INTERVENTIONS: Using a hand-held probe (CeramOptic),
      and the HGM argon laser, the anterior crus of the stapes was vaporized. Next, a
      linear stapedotomy was made across the anterior one third of the footplate. If
      otosclerosis is confined to the fissula antefenestram, the stapes becomes
      completely mobile. The stapedotomy opening is sealed with an adipose tissue graft
      from the ear lobe. MAIN OUTCOME MEASURES: Pure-tone audiometry with appropriate
      masking and auditory discrimination testing were performed before surgery, 6
      weeks after surgery, and 1 year after surgery. RESULTS: The average air-bone gap
      was closed to a mean (SD) of 2.6 dB (3.3 dB). The average improvement in air-bone
      gap was 17.4 dB (7.6 dB). The discrimination scores remained unchanged.
      Audiometric testing of five cases with 1 year follow-up demonstrates that
      excellent hearing results are maintained. CONCLUSIONS: In selected cases of
      minimal otosclerosis confined to the fissula antefenestram, normal mobility of
      the ossicular chain can be obtained without a prosthesis by vaporizing the
      anterior crus and making a linear stapedotomy across the anterior one third of
      the footplate. The advantages of the procedure are that the stapedius tendon and
      most of the normal stapes remain intact, eliminating hyperacusis. The procedure
      is less invasive so it reduces inner ear trauma, possible prosthesis problems are
      avoided, and postoperative barotrauma risk is minimized. Minimal surgery is done
      for minimal disease. If the stapes refixes at some time in the future, a
      conventional stapedotomy can still be performed.

PMID- 9596176
TI  - An alternative method for dealing with cerebrospinal fluid fistulae in inner ear
      deformities.
AB  - OBJECTIVE: This study aimed to review the management of cerebrospinal fluid (CSF)
      fistulae in the setting of developmental inner ear deformity. STUDY DESIGN: The
      study design was a case review, close examination of preoperative radiology, and
      corresponding intraoperative images. TECHNIQUE: A definitive method of CSF
      fistula closure is described using previously known techniques used commonly in
      skull base surgery. CONCLUSIONS: The use of a multiple-level, reinforced wound
      closure technique is necessary to definitively close CSF fistulae in extreme
      inner ear deformity and to prevent further episodes of CSF leak and meningitis.

PMID- 9596175
TI  - Facial nerve injury in congenital aural atresia surgery.
AB  - OBJECTIVE: This study aimed to determine those patients who have sustained a
      facial nerve injury during surgery for congenital aural atresia and pinpoint the
      site of injury vis-a-vis the operative approach. STUDY DESIGN: The study design
      was a retrospective review of >1,000 patients undergoing atresia repair. SETTING:
      The study was performed at a tertiary referral center. PATIENTS: The study
      consists of 10 patients with a facial nerve injury from atresia surgery.
      INTERVENTION: In 1 of 10 patients, the facial nerve was transected. This occurred
      during the skin incision at the level of the helix. A sural nerve cable graft was
      used to repair the severed nerve. MAIN OUTCOME MEASURES: High-resolution computed
      tomography of the temporal bone was the most important preoperative study.
      However, in cases of aural stenosis with cholesteatoma, the course of the facial
      nerve may be camouflaged. RESULTS: Ten of >1,000 patients operated on sustained a
      facial nerve injury from atresia surgery. Seven of these patients were those of
      the authors, whereas three had the initial surgery elsewhere, each by a different
      surgeon. CONCLUSIONS: For the inexperienced surgeon, the facial nerve is at its
      greatest risk in the inferoposterior portion of atretic bone just lateral to the
      middle ear. For the experienced surgeon, the facial nerve is at its greatest risk
      in those patients with low-set ears, canal stenosis, and an accompanying
      cholesteatoma.

PMID- 9596177
TI  - The origin of congenital cholesteatoma.
AB  - OBJECTIVE: This study aimed to document histologically the origin of congenital
      cholesteatoma in neonatal temporal bones. STUDY DESIGN: The study design was a
      systematic analysis of pediatric temporal bones. SETTING: The study was performed
      at the temporal bone laboratory, Tufts University School of Medicine and New
      England Medical Center, Boston, Massachusetts. RESULTS: We describe histologic
      findings of a congenital cholesteatoma and a squamous epithelial rest in two
      postpartum patients. In both patients, the masses were asymptomatic and occurred
      in the anterosuperior quadrant of the middle ear cleft. This is the first
      histologic documentation of postpartum congenital cholesteatoma. CONCLUSIONS: We
      believe that these cases represent the first clear histologic documentation of
      the origin of congenital cholesteatoma.

PMID- 9596178
TI  - Yolk sac tumor of the ear in a child.
AB  - OBJECTIVE: This study aimed to describe the clinical, histopathologic, and
      immunohistochemical findings of the second case of an endodermal sinus tumor of
      the ear. STUDY DESIGN: This clinical study is a retrospective case report
      combined with a literature review. SETTING: The patient was treated at the
      University Erasmus Hospital. INTERVENTION: Diagnosis was confirmed by computed
      tomographic scan and histologic analysis. The treatment was surgical. RESULTS:
      The patient underwent surgical treatment, and a locoregional relapse developed.
      The clinical evolution was in accordance with previous reports of extragonadal
      endodermal sinus tumor sites. The family refused chemotherapy, and the patient
      died 3 months after admission. CONCLUSIONS: An endodermal sinus tumor is a
      malignant germ cell tumor that usually involves the gonadal tissue. Extragonadal
      sites are rare, and different hypotheses have been evoked to explain these
      locations. Treatment options include surgical removal and chemotherapy. This is
      the second case of an endodermal sinus tumor of the ear.

PMID- 9596179
TI  - Pediatric tympanoplasty of iatrogenic perforations from ventilation tube therapy.
AB  - OBJECTIVES: This study aimed to determine surgical outcome of tympanoplasty in
      children with iatrogenic perforations, to determine whether age is a factor in
      successful tympanoplasty, and to determine whether surgical outcome is affected
      by preoperative factors (e.g., perforation size and location, otorrhea,
      cholesteatoma, and tympanosclerosis) or surgical technique (e.g., underlay or
      overlay). STUDY DESIGN: The study design was a retrospective series review.
      SETTING: The study was conducted at a multiphysician private otologic practice.
      PATIENTS: Ninety-three pediatric patients with iatrogenic perforations caused by
      the insertion of ventilation tubes for otitis media with effusion (OME)
      participated. Surgical selection criteria included a year's observation of the
      perforation with a 6-month OME-free interval in the involved and contralateral
      ear. The 46 males and 47 females had a mean age at surgery of 10.8 years
      (standard deviation = 2.9) ranging from 3-16 years. INTERVENTIONS: All patients
      underwent underlay or overlay tympanoplasty using temporalis fascia grafts. MAIN
      OUTCOME MEASURES: Outcome was evaluated in terms of drum healing (healed or
      perforated), hearing (air-bone gap), and complications. RESULTS: There was a
      graft take-rate of 94.6% with reperforations occurring in 5.4% with an average
      follow-up of 16.8 months. Duration of follow-up ranged from 10.8-77.5 months. The
      air-bone gap was completely closed in 53.8% and was closed to within 10 dB in
      80.7% and 20 dB in 94.7%. The incidence of major and minor complications was
      16.1%. Surgical outcome was not influenced by age, technique, or any of the
      preoperative factors. CONCLUSIONS: Tympanoplasty of persistent perforations after
      ventilation tube therapy for recurrent OME can be performed successfully
      regardless of age, surgical technique, or other preoperative factors.

PMID- 9596180
TI  - Hearing loss with cochlear modiolar defects and large vestibular aqueducts.
AB  - OBJECTIVE: Defects of the cochlear modiolus have been found to be associated with
      most cases of large vestibular aqueduct. The clinical significance of these
      modiolar defects has not been studied previously. The purpose of this article is
      to correlate clinical (functional) parameters, such as hearing outcomes, with the
      severity of the radiographic findings in these dysplastic inner ears. STUDY
      DESIGN: The study design was a retrospective chart review, supplemented with
      telephone interviews and clinic visits. SETTING: The study was conducted at an
      academic, tertiary care center. PATIENTS: Thirty consecutive patients with large
      vestibular aqueducts participated. RESULTS: Scores of modiolar deficiencies
      yielded inconsistent correlations with hearing loss. Vestibular aqueduct
      morphology and thickness correlated very strongly with the severity of hearing
      loss. CONCLUSIONS: These observations support the hypothesis that large
      vestibular aqueduct-related hearing loss may be caused by transmission of
      subarachnoid pressure forces into the inner ear. However, the thickness and
      morphology of the vestibular aqueduct may simply be markers for more subtle
      cochlear dysplasia manifest by modiolar deficiency.

PMID- 9596181
TI  - Performance with the 20 + 2L lateral wall cochlear implant.
AB  - OBJECTIVE: The purpose of this study was to investigate the operating
      characteristics of the Nucleus 20 + 2L lateral wall cochlear implant including
      speech recognition results. STUDY DESIGN: This was a prospective randomized study
      involving five different modes of stimulation. SETTING: This study was carried
      out in an academic, tertiary referral center. PATIENTS: The patients included in
      this study were adult cochlear implant candidates ages 44-74 years. Length of
      deafness ranged from 1 to 58 years with a variety of etiologies. INTERVENTIONS:
      All patients were implanted with a 20 + 2L implant, which includes an intrascalar
      electrode array and an apically placed extracochlear, titanium encased ball
      electrode in contact with the endosteum of the apical turn. All patients
      underwent psychophysical and speech recognition testing in five different modes
      of electrode configuration. MAIN OUTCOME MEASURE(S): The main outcome measures
      included thresholds, comfort levels, dynamic ranges, and speech recognition
      results obtained in five electrode configuration modes. RESULTS: Thresholds were
      significantly lower (repeated measures ANOVA) in both monopolar conditions when
      compared to bipolar mode of stimulation. A binomial statistical analysis
      indicated that in five of nine patients activated in all five modes of
      stimulation, the monopolar modes of stimulation resulted in improved speech
      recognition scores. CONCLUSIONS: The results of the study demonstrate the
      feasibility of the use of an apical lateral cochlear wall electrode in
      conjunction with an intrascalar electrode array. It further demonstrated the
      superiority of monopolar stimulation in selected patients.

PMID- 9596182
TI  - Preliminary experience with neural response telemetry in the nucleus CI24M
      cochlear implant.
AB  - OBJECTIVE: This study aimed to compare recordings of the electrically evoked
      whole nerve action potential (EAP) made using the reverse telemetry system of the
      Nucleus CI24M device with those recorded from individuals who use the Ineraid
      cochlear implant system. STUDY DESIGN: Data were collected in a prospective
      fashion from Nucleus CI24M cochlear implant users and compared with retrospective
      data collected from patients who use the Ineraid device. SETTING: All data were
      collected at the Department of Otolaryngology-Head and Neck Surgery, University
      of Iowa Hospitals and Clinics. PATIENTS: Data are reported from 8 patients who
      use the Nucleus CI24M cochlear implant and 20 patients who use the Ineraid
      cochlear implant system. INTERVENTIONS: The interventions described in this study
      were diagnostic in nature. MAIN OUTCOME MEASURES: EAP growth and refractory
      recovery data are reported. EAP thresholds recorded from patients who use the
      Nucleus CI24M device also are compared with behavioral thresholds for the
      stimulus used to evoke the EAP as well as the stimulation levels needed to
      program the speech processor. RESULTS: EAP morphology, growth, and refractory
      recovery functions recorded using the Nucleus CI24M reverse telemetry system
      compared favorably with similar measures recorded from Ineraid cochlear implant
      users. CONCLUSIONS: Reasonable EAP responses can be recorded using the Nucleus
      CI24M device. More data are needed to determine whether the information about
      neural responsiveness available with this device will be clinically useful.

PMID- 9596183
TI  - Cochlear implants in children: an analysis of use over a three-year period.
AB  - OBJECTIVE: This study aimed to determine whether children continue to wear their
      cochlear implant systems 1 and 3 years after implantation. STUDY DESIGN: The
      design was a prospective study based on the analysis of forced-choice
      questionnaires on implant use completed independently by parents and teachers.
      SETTING: The study was performed at a dedicated pediatric cochlear implant
      program in a tertiary referral center in the United Kingdom. PATIENTS: All 85
      consecutively implanted children who had reached the 1-year interval after
      implantation and 37 children who had reached the 3-year assessment interval after
      implantation participated. The patients represented all socioeconomic status
      groups, the entire range of educational settings, and often lived at a
      considerable distance from the implant center. MAIN OUTCOME MEASURES: Parents and
      local teachers were asked to describe implant use in the following categories: 1)
      all of the time; 2) most of the time; 3) some of the time; and 4) none of the
      time. RESULTS: One year after implantation, parents and teachers, respectively,
      rated 79 (93%) and 82 (96%) children as full-time users (category 1). Parents
      rated six children (7%) as users most of the time (category 2), and teachers
      rated three children (4%) as users most of the time. No child was rated as an
      occasional or nonuser (category 3 or 4). At 3 years after implantation, 33 (89%)
      and 34 (95%) children were rated as full-time users (category 1) by parents and
      teachers, respectively. Parents judged four children (11%) and teachers rated two
      children (5%) to be users most of the time (category 2). Again, no child was
      rated in category 3 or 4 as an occasional or nonuser. CONCLUSIONS: The majority
      of implanted children use their implant systems all of the time over a 3-year
      period after implantation when selected appropriately and given appropriate
      follow-up.

PMID- 9596184
TI  - Indications and counterindications for cochlear implantation in children.
AB  - OBJECTIVE: This study is aimed to analyze the current indications and
      counterindications of cochlear implantation (CI) in children. STUDY DESIGN: This
      study reviews the children implanted in our institution looking specifically at
      the following aspects: 1) auditory criteria for candidate selection; 2) age at
      implantation; 3) educational environment; and 4) associated handicapping
      conditions. SETTING: Tertiary referral center with experience in CI since 1989
      with inpatient and outpatient care. INTERVENTION: All children received a Mini
      Nucleus 22 CI device (Cochlear Limited, Australia) in a standard surgical
      procedure. RESULTS: Regarding auditory criteria, children with average hearing
      level of 100-105 dB HL are more likely to obtain benefit from a CI than from a
      hearing aid. The minimum age for CI should be as soon as there is a reliable
      diagnosis of bilateral profound hearing loss, while the maximum age for CI
      depends on strict selection criteria of candidates. The educational environment
      is of a great importance in the rehabilitation process, permitting a progressive
      change to oral communication. Our experience in CI of children with multiple
      handicapping conditions is limited to a case of a deaf-blind child who was
      implanted with a good performance. In the selection of these children it is
      mandatory to have extensive multidisciplinary evaluation. CONCLUSIONS: An
      experienced team is needed in the selection of children for CI. Candidates should
      meet anatomic criteria, have a reliable diagnosis of bilateral profound hearing
      loss, an evaluation of communication skills, and extensive neuropediatric and
      socioeducational evaluation.

PMID- 9596185
TI  - The role of endolymphatic mastoid shunt surgery in the managed care era.
AB  - OBJECTIVE: Ongoing controversy regarding the surgical management of Meniere's
      disease has prompted us to review the effectiveness of the endolymphatic mastoid
      shunt procedure in the control of vertigo. In the current managed care
      environment in which outcome measures, cost effectiveness, and procedural
      efficacy must be demonstrated, the surgeon can no longer rely on anecdotal or
      empirical observations regarding the effectiveness of a treatment paradigm. STUDY
      DESIGN: Retrooperative case review. SETTING: A tertiary care center. PATIENTS:
      The records of 327 patients with presumed Meniere's-related vertigo referred to
      the University of Cincinnati Medical Center were reviewed. One hundred nine
      patients underwent endolymphatic mastoid shunt. Our study population consists of
      96 of these patients that were available for 5 years follow-up. INTERVENTIONS:
      Endolymphatic mastoid shunt for the control of medically refractory vertigo. MAIN
      OUTCOME MEASURE: Control of vertigo. RESULTS: Using the Arenberg anatomic
      classification system, patients with a type I endolymphatic sac achieved 68%
      control of vertigo, those with a type II endolymphatic sac had a 92% control
      rate, and patients with a type III endolymphatic sac achieved 78% relief.
      CONCLUSIONS: Based on an assessment of outcome variables, we conclude that there
      remains a definite role for endolymphatic shunt surgery in the contemporary
      approach to patients with Meniere's disease.

PMID- 9596186
TI  - Retrospective blinded review of magnetic resonance imaging in patients with
      central electronystagmography findings.
AB  - OBJECTIVE: To evaluate the magnetic resonance imaging results (MRI) of patients
      with electronystagmography (ENG) suggestive of central vestibular dysfunction and
      to determine if MRI abnormalities correlate with ENG findings. STUDY DESIGN:
      Retrospective blinded case review. SETTING: A regional neurotology center.
      PATIENTS: Patients with ENG suggesting central vestibular dysfunction were
      identified (n = 30). An age-matched group of patients with normal ENG results
      were used as controls (n = 28). MAIN OUTCOME MEASURES: MRI abnormalities in
      cerebellum, brain stem, cerebellar peduncles, and central ENG findings. RESULTS:
      Twenty-one patients with abnormal MRI results of the vestibular pathway were
      found, 15 with abnormal and 6 with normal ENG results. MRI correlation with ENG
      findings has a better predictive value in older patients than in younger
      patients. Sixteen patients had MRI evidence of vascular compression, seven of
      whom had abnormal and nine of whom had normal ENG results. CONCLUSIONS: This
      study suggests that a detailed review of MRI images of the vestibular pathway is
      warranted, and, in patients with central ENG abnormalities, MRI may support the
      diagnosis of central vestibular dysfunction. MRI cannot support central
      vestibular dysfunction caused by vascular compression.

PMID- 9596187
TI  - Recognition and management of horizontal canal benign positional vertigo.
AB  - OBJECTIVE: We reviewed the features of nystagmus in 24 patients with horizontal
      canal benign positional vertigo (BPV). Patients were treated with canalith
      repositioning maneuvers. Our goal was to develop a framework for distinguishing
      horizontal from posterior canal BPV and to further develop a mechanistic model
      explaining the horizontal canal variant of BPV. STUDY DESIGN: The study design
      was a retrospective case review with prospective treatment outcome and follow-up.
      SETTING: The study was performed at a secondary and tertiary referral center for
      vertigo and dizziness. PATIENTS: The diagnosis of horizontal canal BPV was based
      on: 1) recurrent brief episodes of positional vertigo; 2) paroxysmal bursts of
      horizontal positional nystagmus; and 3) lack of any other identifiable central
      nervous system disorder to explain the nystagmus. Patient average age was 62
      years, and average duration of symptoms was 12 weeks. INTERVENTIONS: We
      documented patients' symptoms and the characteristics of nystagmus. We reviewed
      the effectiveness of several similar canalith repositioning treatments. MAIN
      OUTCOME MEASURE: We observed and recorded factors that distinguish horizontal
      from posterior canal BPV. We monitored the direction of nystagmus, the type of
      maneuver that evoked the nystagmus, and the response to canalith repositioning.
      RESULTS: Symptom description alone was not sufficient to distinguish among canal
      types of BPV. Horizontal geotropic direction-changing positional nystagmus was
      observed in 19 of 24 patients. The other patients had ageotropic nystagmus. Both
      types were distinct from the nystagmus of posterior canal BPV. Response to
      canalith repositioning was 75% at 1 week of follow-up. Conversion of BPV from one
      canal to another occurred in some patients, but each canal could be treated
      individually. CONCLUSIONS: Patients with positional vertigo should undergo Dix
      Hallpike positioning and supine lateral head turns to each side. Paroxysmal
      positional horizontal nystagmus that changes direction with changes in head
      position strongly suggests the diagnosis. Canalith repositioning for posterior
      canal BPV may fail in horizontal BPV. A 360 degrees barbecue rotation toward the
      presumably healthy ear done two to four times or until nystagmus disappears may
      result in more rapid resolution of symptoms.

PMID- 9596188
TI  - Audiologic presentation of vestibular schwannomas in neurofibromatosis type 2.
AB  - OBJECTIVE: The audiologic presentation of vestibular schwannoma (VS) associated
      with neurofibromatosis type 2 (NF2) has not been well characterized. The goal of
      this study was to investigate the audiologic features of NF2-associated VS and to
      determine their relationship to the size of the tumor. STUDY DESIGN: A
      retrospective case review. SETTING: Quaternary governmental medical research
      institute evaluating patients fitting specific criteria for ongoing clinical
      studies. PATIENTS: Audiologic and magnetic resonance imaging data were available
      for 40 patients (25 males, 15 females), with an average age of 32 years, who had
      been recruited for ongoing clinical and genetic studies of NF2. MAIN OUTCOME
      MEASURES: The audiologic profile and magnetic resonance imaging characteristic of
      tumor were retrospectively reviewed. RESULTS: The average size of the tumor at
      presentation was 7.26 +/- 16.58 cm3 and measured 1.2, 1.6, and 1.1 cm in the
      anterior/posterior, lateral/medial, and superior/inferior dimensions,
      respectively. An increase in lateral/medial size of the tumor most significantly
      correlated with deterioration in mid- (1,000-2,000 Hz) and high- (4,000-8,000 Hz)
      frequency hearing levels, elevated speech reception threshold, and prolonged
      auditory brain stem response waves III and V latency. CONCLUSIONS: Patients with
      NF2 demonstrate a more predictable audiologic profile for a given size tumor than
      has been previously described with spontaneous or sporadic VS.

PMID- 9596189
TI  - Anatomy and significance of the subarachnoid space in the fallopian canal.
AB  - OBJECTIVE: To describe the anatomic variations of the subarachnoid space (SAS) in
      the facial nerve canal from human temporal bone specimens. BACKGROUND: The SAS in
      the facial canal usually is assumed to terminate in the petrosal segment of the
      canal. This temporal bone study indicates that in 12% of temporal bones the SAS
      extends laterally into or beyond the tympanic segment of the facial canal.
      METHODS: Histologic sections through the petrosal and tympanic segments of the
      facial canal were examined by light microscopy in 1 fetal (30 weeks) and 163
      adult human temporal bones. The arachnoidal membrane of the SAS was judged to
      fall into three types according to its lateral extension in the fallopian canal.
      RESULTS: One hundred forty-four (88%) of the adult temporal bones contained an
      SAS limited to the petrosal fallopian canal (type I). Thirteen temporal bones
      (8%) demonstrated an SAS that extended into the tympanic or geniculate portions
      of the facial nerve (type II). There were six temporal bones (4%) in which the
      SAS extended lateral to the tympanic facial nerve or into a separate bony
      compartment (type III). CONCLUSIONS: Most (88%) temporal bones contain an SAS
      that is limited to the petrosal fallopian canal. In 12% of temporal bones,
      however, the SAS may extend laterally in the fallopian canal and present
      clinically as an asymptomatic enlargement of the canal by computed tomography or
      as cerebrospinal fluid otorrhea.

PMID- 9596190
TI  - Orthodromic near-field potentials of the intratemporal facial nerve.
AB  - HYPOTHESIS: This study aimed to assess the electrophysiologic parameters of near
      field action potentials recorded from the intratemporal facial nerve. BACKGROUND:
      Assessment of facial nerve function is limited because of the inaccessibility of
      the majority of its course deep in the temporal bone. Indirect measurements have
      therefore evolved in which stimulation distal to most major pathology and
      indirect recordings from the tissues the nerve supplies offers some evidence as
      to facial function. Recording from the intratemporal portion of the facial nerve
      is possible. Antidromic nerve action potentials can be recorded from an
      extratympanic electrode after stimulation of peripheral facial nerve branches.
      This technique offers new alternatives to the assessment of the facial nerve.
      METHODS: The facial nerve was electrically stimulated close to the brain stem,
      and monopolar recordings were taken distally at several points along its
      intratemporal course. Averaging techniques produced a reliable and reproducible
      triphasic waveform that then was analyzed. RESULTS: Neuromuscular blockade had no
      effect on amplitude of the waveform. Recording at different points along the
      nerve course showed an increasing nerve potential latency with increasing
      distance from the stimulus. The amplitude of the waveform decreased as the
      recording electrode was moved away from the nerve. These findings are in keeping
      with the electrophysiologic properties of a near-field nerve action potential.
      Conduction velocity along the facial nerve averaged 23.7 m/s and was found to
      vary along different nerve segments. CONCLUSION: Facial nerve action potentials
      can be recorded from within the temporal bone despite its multidirectional course
      through different volume conductors. These action potentials exhibit the same
      characteristics as those arising from more accessible peripheral nerves.

PMID- 9596191
TI  - The history of otology through its eponyms I: anatomy.

PMID- 9596193
TI  - Imaging case of the month: inner ear malformation.

PMID- 9596192
TI  - Expression of adeno-associated virus integrated transgene within the mammalian
      vestibular organs.
AB  - HYPOTHESIS: Adeno-associated virus (AAV) is a suitable viral vector for transgene
      expression within the mammalian vestibular organs. BACKGROUND: In vivo
      introduction and expression of a foreign gene within the cochlear tissues have
      been established using a variety of viral vectors and guinea pig as the animal
      model. However, the vestibular neuroepithelia of the mammalian inner ear as a
      potential target for transgene expression remain to be investigated. METHODS:
      Transgene expression was assessed within the vestibular neuroepithelia of guinea
      pigs after intracochlear infusion of the recombinant AAV vector with the aid of
      an osmotic minipump. Evaluation of the transgene within the vestibular apparatus
      focused on its duration of expression from 2-24 weeks after intracochlear AAV
      infusion using immunohistochemistry. RESULTS: In the AAV-beta-galactosidase (beta
      gal)-infused animals, the sensory hair cells as well as the supporting epithelial
      cells of cristae and maculae were positive for the transgene expression. The
      relative level of beta-gal expression was noted to decrease progressively over
      time. Transduction of the vestibular neuroepithelia also was observed in the
      contralateral ear, a finding that has been documented previously in AAV
      integrated transgene expression in the cochlea. CONCLUSION: This study reports
      the first demonstration of introduction and long-term transgene expression within
      the vestibular neuroepithelia. The ability to express a foreign gene with the
      vestibular system allows the possibility of experimental and therapeutic
      application of gene therapy technology to address vestibular function and
      dysfunction.

PMID- 9596194
TI  - Temporal bone histopathology case of the month: otosclerosis.

PMID- 9596195
TI  - Nonepileptic psychogenic seizures: quagmires of pathophysiology, diagnosis, and
      treatment.

PMID- 9596196
TI  - Developmental background and outcome in patients with nonepileptic versus
      epileptic seizures: a controlled study.
AB  - PURPOSE: This study was designed to evaluate the relevance of developmental
      emotional stress factors, which are considered to influence emotional
      functioning, as contributing factors in the development of psychogenic symptoms.
      METHODS: Ten patients with nonepileptic seizures (non-ESs) (frequently referred
      to as psychogenic seizures), in whom diagnosis had been confirmed by a placebo
      infusion test (PT), and 10 control patients with complex partial seizures (ESs)
      were evaluated with regard to developmental background by using structured in
      depth interviews performed by a single interviewer blinded to the diagnosis. In
      addition, outcome assessment in the non-ES group after PT was done. RESULTS:
      There were no significant differences between groups in developmental
      psychosocial stress or in any single developmental stress factor. Six months
      after PT, the outcome was favorable in patients with non-ES: six were seizure
      free, and two had a considerable reduction in frequency of seizures. CONCLUSIONS:
      Our research indicates the following: (a) a high incidence of developmental
      stress factors and functional disturbances may be found in patients with non-ESs
      and ESs; (b) assessment of developmental emotional stress and functional
      disturbances as a basis for validating the diagnosis of non-ES should be treated
      with caution; (c) use of PT followed by supportive information about the
      nonepileptic origin of the attacks may have a positive therapeutic effect or help
      to introduce psychotherapeutic treatment.

PMID- 9596197
TI  - Retrospective analysis of the effects of psychotherapeutic interventions on
      outcomes of psychogenic nonepileptic seizures.
AB  - PURPOSE: Uncertainty exists regarding the effectiveness of psychotherapy in
      patients with psychogenic nonepileptic seizures (PNES). We retrospectively
      reviewed the outcomes of therapeutic interventions in a cohort of patients with
      PNES. METHODS: We identified patients with PNES by outpatient video-EEG (VEEG)
      between 1992 and 1996. We retrospectively analyzed the effects on outcomes of
      various types of interventions for PNES administered at random, using a
      structured interview and review of medical records. Patients with subjective
      events and severe psychosis were excluded. Patients who required inpatient
      monitoring because the outpatient VEEG was inconclusive were also excluded.
      RESULTS: One hundred patients were diagnosed with PNES between 1992 and 1996: 61
      patients completed the study. The average age was 43.3 years, and 90% were
      female. Nine (15%) had had PNES <1 year, and 7 (11%) had epilepsy. Eleven of 16
      patients (68%) who received five or more counseling sessions, including showing
      the videotaped recording of the nonepileptic spell (13 of 16) by the
      comprehensive epilepsy program (CEP) psychotherapist had cessation (7 of 16) or
      reduction (4 of 16) of their episodes. Eleven of 15 patients (73%) who received
      only the feedback and care of their CEP neurologists had similar favorable
      outcome. Twelve of 25 patients (48%) who received counseling by a non-CEP
      psychotherapist or psychiatrist had cessation (10 of 25) or reduction (2 of 25)
      of episodes. Five patients who received no feedback or intervention had no
      improvement (4 of 5) or worsening (1 of 5) of the PNES. CONCLUSIONS:
      Psychotherapy or feedback provided by CEP professionals with experience in
      epilepsy and PNES improves outcome and may be superior to other or no
      interventions.

PMID- 9596198
TI  - De novo psychogenic nonepileptic seizures after epilepsy surgery.
AB  - PURPOSE: The occurrence of de novo nonepileptic seizures (NES) after epilepsy
      surgery have been reported only twice in the literature (one article and one
      abstract). METHODS: We report three patients whose de novo NES were documented by
      video-EEG telemetry after epilepsy surgery. These patients were drawn from a
      sample of 166 consecutive patients who underwent epilepsy surgery at our center
      between 1989 and 1996. RESULTS: Two patients became seizure free after surgery,
      and one had significant improvement of her seizures. The interval between the
      date of surgery and the development of the symptoms was variable (8, 10, and 47
      months, respectively). The clinical phenomena of NES differed from those of the
      epileptic seizures preceding surgery. Their diagnosis had not been suspected in
      two patients before the diagnostic video-EEG monitoring study. After the
      diagnosis of NES, spells stopped in two patients and recurred rarely in one.
      CONCLUSIONS: We conclude that de novo NES appears to occur rarely after epilepsy
      surgery. Given that the possibility of NES was suspected in only one patient, its
      incidence after surgery may be higher than so far reported. Physicians should
      therefore consider NES in the differential diagnosis of recurrent seizures after
      a seizure-free period after epilepsy surgery.

PMID- 9596199
TI  - Psychiatric outcome of temporal lobectomy for epilepsy: incidence and treatment
      of psychiatric complications.
AB  - PURPOSE: To determine the incidence of psychiatric disorders before and after
      surgical treatment for partial epilepsy and to document the effectiveness of
      their treatment. METHODS: Fifty consecutive patients treated surgically for focal
      epilepsy (44 temporal and six frontal) were evaluated by established
      neuropsychiatric methods before surgery and over a mean period of 2 years after
      surgery. The patients with interictal dysphoric disorders, with or without
      psychotic episodes, were treated with tricyclic antidepressant medication alone
      or combined with serotonin selective reuptake inhibitors and, if necessary, with
      the addition of risperidone. RESULTS: Before surgery, 25 (57%) of the 44 patients
      with temporal lobe epilepsy had dysphoric disorders. After surgery, 17 (39%) of
      the 44 patients experienced either de novo psychiatric complications (six
      psychotic episodes, six dysphoric disorders, and two depressive episodes) or
      exacerbation of preoperative dysphoric disorder (three patients). Eight
      previously intact patients of the 19 (42%) developed dysphoric disorders after
      surgery that were significantly related to recurrence of seizures. All
      psychiatric complications occurred in the first 2 months after surgery, except
      for the six patients intact before surgery, who had a recurrence of seizures. A
      significant predictor of ultimate excellent psychiatric outcome was complete
      absence of seizures after surgery. All postoperative psychiatric complications
      remitted on treatment with psychotropic medication in the compliant patients.
      CONCLUSIONS: An exceptional psychiatric morbidity is associated with the months
      after temporal lobectomy. Possible pathogenetic mechanisms are discussed.
      Antidepressant drugs are very effective in treating the psychiatric disorders of
      chronic epilepsy; their use in conjunction with the surgical treatment of
      epilepsy appears to be crucial for the overall positive outcome of a significant
      number of patients.

PMID- 9596200
TI  - Presurgery expectations, postsurgery satisfaction, and psychosocial adjustment
      after epilepsy surgery.
AB  - PURPOSE: The medical benefits of epilepsy surgery are well documented, but the
      psychosocial consequences of surgery have received less attention. This is
      especially true of the roles of expectations and satisfaction in postsurgery
      functioning. The present study was designed to examine the relationships between
      expectation, satisfaction with surgery, and psychosocial functioning in patients
      and their significant others before and after epilepsy surgery. METHODS: The
      neuropsychology findings of 79 patients undergoing epilepsy surgery were examined
      from assessments made before, 2 months after, and 1 year after anterior temporal
      lobectomy (ATL) was performed. The Minnesota Multiphasic Personality Inventory
      (MMPI) and the Washington Psychosocial Seizure Inventory (WPSI) were used to
      assess psychosocial functioning. A subset of 32 patients and their significant
      others were followed prospectively with an additional semistructured interview to
      assess expectations for and satisfaction with surgery outcome. RESULTS: Before
      surgery, patients showed considerable problems with psychosocial adjustment.
      After surgery, patients in the seizure-free group showed improvements on the
      psychosocial measures at both follow-ups, whereas patients with continued
      seizures showed improvement at the 2-month follow-up and then a decline to
      baseline or worse at the time of the 1-year follow-up. Subjects who were studied
      prospectively had high presurgery expectations for seizure elimination. After
      surgery, subjects whose expectations were met reported high satisfaction whereas
      subjects whose expectations were not met reported low satisfaction. Satisfaction
      with surgery was associated with better psychosocial functioning. CONCLUSIONS:
      Such data help elucidate the ways in which successful epilepsy surgery results in
      improved psychosocial functioning. The results identify ways to increase the
      likelihood that both patients who are seizure-free and those with reduced seizure
      frequency may benefit from surgery.

PMID- 9596201
TI  - The efficacy of lamotrigine in children and adolescents with refractory
      generalized epilepsy: a randomized, double-blind, crossover study.
AB  - PURPOSE: We report a double-blind, placebo-controlled crossover study of
      lamotrigine (LTG) as add-on treatment in therapy-resistant, generalized epilepsy
      in children and adolescents (n = 30). METHODS: Twenty patients had Lennox-Gastaut
      syndrome. Each patient acted as his or her own control. LTG and placebo were
      randomly added to existing antiepileptic medication (AEDs). The LTG dosage was
      individualized in an open phase preceding the placebo/treatment phase. Patients
      who responded to LTG in the open phase went on to the double-blind phase.
      "Responders " were defined as patients with a >50% seizure reduction or less
      severe seizures or both, or improved behavior or improved motor skills or both.
      "Nonresponders" were defined as children who showed no positive effects of LTG
      with plasma levels of < or = 10 microg/ml or children who had adverse events
      during the open phase. RESULTS: There was a clear statistically significant
      reduction of seizure frequency in LTG compared with placebo treatment. None of
      the children studied showed abnormal biochemical or hematologic findings, or
      changes in plasma levels of concomitantly administered AEDs. CONCLUSIONS: LTG is
      a well-tolerated and effective treatment in children with intractable generalized
      epilepsies, including those with Lennox-Gastaut syndrome. The study design
      allowed a double-blind placebo-controlled assessment of LTG although the
      participating children used 19 different AED combinations at entry.

PMID- 9596202
TI  - Lamotrigine hypersensitivity in childhood epilepsy.
AB  - PURPOSE: To evaluate the effect of lamotrigine (LTG) on several humoral and
      cellular immune functions in children with epilepsy and the change in
      immunological status in patients with LTG-induced rash. METHODS: Sixteen children
      with epilepsy of unknown origin or secondary to various etiologies undergoing
      treatment with LTG participated in the humoral and cellular immunological study.
      Of these, 2 patients developed a rash during LTG treatment and are described in
      detail. RESULTS: No modifications of humoral or cellular immunity (measured at 1
      and 3 months) were noted in 14 of the 16 patients during this treatment. In the 2
      children who manifested rash, basal immune function was normal. In both,
      immediately after the skin rash appeared, there was a high increase in the
      percentage of activated T-helper lymphocytes (CD4-DR) and activated T-suppressor
      lymphocytes (CD8-DR), a slight increase in percentage of B lymphocytes (CD19),
      and a greater increase in serum concentration of IgE. In 1 of the 2 patients,
      reevaluation of immunity 20 days after the rash appeared and after LTG suspension
      showed normal percentages of CD4-DR, CD8-DR, and CD19, whereas the serum
      concentration of IgE had decreased. CONCLUSIONS: The observed immunological
      results indicate that LTG-induced rash may be considered an immune-mediated
      hypersensitivity reaction.

PMID- 9596203
TI  - Lamotrigine and seizure aggravation in severe myoclonic epilepsy.
AB  - PURPOSE: In severe myoclonic epilepsy of infancy (SME), multiple drug-resistant
      focal and generalized seizure types occur. Lamotrigine (LTG), found effective in
      many generalized and partial seizures, has been little used in severe childhood
      epilepsy syndromes with multiple seizure types. We studied the effects of LTG in
      SME. METHODS: Twenty-one patients with SME, aged 2-18 years, were treated with
      LTG, 20 in add-on and one in monotherapy. LTG was started at 0.2-2.5 mg/kg/day
      and increased to 2.5-12.5 mg/kg/day. For each seizure type, excluding atypical
      absences, >50% variations compared with the 2 months preceding LTG were
      considered indicators of response, also taking into account the degree of
      disability each seizure type produced. RESULTS: LTG induced worsening in 17 (80%)
      patients, no change in three, and improvement in one. There was >50% increase in
      convulsive seizures in eight (40%) of 20 patients. Myoclonic seizures worsened in
      six (33%) of 18 patients. Of five patients improving in at least one seizure
      type, four had concomitant worsening of more invalidating seizures. Clear-cut
      worsening appeared within 3 months in most patients but was insidious in some.
      LTG was suspended in 19 patients after 15 days-5 years (mean, 14 months) with
      consequent improvement in 18. CONCLUSIONS: The pronounced seizure deterioration
      during LTG treatment was not attributable to the natural course of the disease
      and could be a direct effect of therapeutic LTG doses. LTG treatment seems
      inappropriate in SME.

PMID- 9596204
TI  - Criteria to assess in vivo performance and bioequivalence of generic controlled
      release formulations of carbamazepine.
AB  - PURPOSE: Concern persists that the criteria used to establish bioequivalence of
      generic drugs may not adequately guarantee the interchangeability of
      antiepileptic medications (AEDs), particularly controlled-release (CR)
      formulations. We examined the utilization of several new parameters, in addition
      to AUC, peak plasma concentration (Cmax), and time to reach Cmax (tmax), for the
      assessment of bioequivalence and in vivo performance of CBZ and other CR
      products. These new parameters may offer additional information for evaluation of
      CR products that yield a prominent plateau in the plasma time-concentration
      curve. They include mean residence time (MRT), Cmax/AUC, plateau time or POT (the
      time span associated with the concentrations within 25% of Cmax), t(apical), and
      C(apical) (the arithmetic mean of the POT times and concentrations within 25% of
      Cmax, respectively). Additional parameters for multiple-dose studies include the
      percentage fluctuation and the flatness of the steady state-concentration curve.
      METHODS: These proposed parameters were used in two recent (single and multiple
      dose) two-way crossover studies of a new CR product of CBZ (Teril 400 CR) in
      comparison with Tegretol CR Divitab. RESULTS: Teril 400 CR was found to be
      bioequivalent to Tegretol CR Divitab, by using both the classic and the
      additional proposed parameters. Both CBZ CR products have similar rates of
      absorption and similar flatness of their plasma time-concentration curves as
      assessed by visual inspection and the proposed parameters. CONCLUSIONS: The
      additional parameters examined may supplement the traditional single-point
      parameters, Cmax and tmax, for assessment of rate of absorption and the flatness
      of the concentration curve. Their potential benefit and practical utility was
      confirmed in these two studies. Absorption-rate assessment is important in light
      of concentration-related side effects associated with CBZ therapy and the impact
      of fluctuations and the flatness of the CBZ plasma concentration curve on the
      drug efficacy and tolerability.

PMID- 9596205
TI  - A single-blind, crossover comparison of the pharmacokinetics and cognitive
      effects of a new diazepam rectal gel with intravenous diazepam.
AB  - PURPOSE: The objective of this study was to compare the pharmacokinetics and
      cognitive effects of a new diazepam (DZP) rectal gel (Diastat) with intravenously
      administered DZP. METHODS: Twenty healthy volunteers were enrolled in a single
      blind, randomized, double-dummy, two-period, crossover study. Subjects received
      either 15 mg of DZP rectal gel or 7.5 mg of DZP by intravenous infusion. Blood
      samples for DZP and desmethyldiazepam analysis were obtained before the dose and
      from 3 min to 240 h after the dose. Heart rate and blood pressure were measured
      over the first 24-h period. Subjects also completed five repetitions of a
      neuropsychological test battery over the first 8-h period. RESULTS: Diazepam
      rapidly appeared in plasma after rectal administration, exceeding 200 ng/mL
      within 15 min and reaching an initial maximum of 373 ng/ml at 45 min and a second
      maximum of 447 +/- 91.1 ng/ml at approximately 70 min. The absolute
      bioavailability of DZP rectal gel was 90.4%. Subjects receiving intravenous DZP
      were less alert and performed less efficiently on the WAIS Digit Symbol test 6
      min after the dose. Subjects receiving DZP rectal gel performed less well on the
      WAIS Digit Span test 1 h after the dose and required more time to complete the
      Letter Cancellation and Grooved Pegboard tests 1 and 2 h after drug
      administration. CONCLUSIONS: Diastat displayed rapid, consistent absorption and
      was well tolerated. Alterations in cognition were mild and dissipated within 4 h
      of drug administration. This new rectal drug-delivery system offers an easy,
      safe, and bioavailable method to administer DZP.

PMID- 9596206
TI  - Regional distribution of interictal 31P metabolic changes in patients with
      temporal lobe epilepsy.
AB  - PURPOSE: We compared the 31P metabolites in different brain regions of patients
      with temporal lobe epilepsy (TLE) with those from controls. METHODS: Ten control
      subjects and 11 patients with TLE were investigated with magnetic resonance
      imaging (MRI) and [31P]MR spectroscopic imaging (MRSI). [31P]MR spectra were
      selected from a variety of brain regions inside and outside the temporal lobe.
      RESULTS: There were no asymmetries of inorganic phosphate (Pi), pH, or
      phosphomonoesters (PME) between regions in the left and right hemispheres of
      controls. In patients with TLE, Pi and pH were higher and PME was lower
      throughout the entire ipsilateral temporal lobe as compared with the
      contralateral side and there were no significant asymmetries outside the temporal
      lobe. The degree of ipsilateral/contralateral asymmetry for all three metabolites
      was substantially greater for the temporal lobe than for the frontal, occipital,
      and parietal lobes, and these asymmetries provided additional data for seizure
      localization. As compared with levels in controls, Pi and pH were increased and
      PME were decreased on the ipsilateral side in patients with TLE. There were
      changes in Pi, pH, and PME on the contralateral side in persons with epilepsy as
      compared with controls, contrary to changes on the ipsilateral side. CONCLUSIONS:
      Our findings provide some insight into the metabolic changes that occur in TLE
      and may prove useful adjuncts for seizure focus lateralization or localization.

PMID- 9596207
TI  - The demand for hospital services for patients with epilepsy.
AB  - PURPOSE: To describe the patterns of inpatient and outpatient hospital care for
      patients with epilepsy in our health district. METHODS: Routine hospital data for
      the health district of South Glamorgan (population 408,000) underwent record
      linkage to identify those records relating to the same patients and to flag those
      records for patients with epilepsy. This data was analyzed to determine inpatient
      and outpatient activity by specialty and compared with the nonepileptic
      population. RESULTS: We identified 2.267 patients representing a prevalence of
      0.56%. The average age was 46 years in both male and female patients. This group,
      which constituted 1.5% of the hospital population, was responsible for 2.8% of
      all admissions but, because of increased length of stay, utilized 7.3% of all bed
      days. The total cost of care for this group lies between these two extreme values
      and is dependent on case severity. The patterns of associated diagnoses differed
      considerably in three arbitrary age groups (0-18, 19-55, >55 years). CONCLUSIONS:
      This study quantifies for the first time the level of demand that this
      subpopulation places on the service as a whole, and begins to illustrate that
      there may be evidence for cost containment by, for example, a reduction in
      multiple admissions. The demand for inpatient services is greater than we would
      have predicted.

PMID- 9596209
TI  - Fixation-off (Scoto) sensitivity combined with photosensitivity.
AB  - A 16-year-old boy of normal intelligence had brief absence and myoclonic jerks
      since age 7 years. Video-EEG documented the unexpected combination of fixation
      off sensitivity (scotosensitivity) with photosensitivity.

PMID- 9596208
TI  - EEG background as predictor of electrographic seizures in high-risk neonates.
AB  - PURPOSE: Experience with continuous EEG monitoring in 29 consecutive infants at
      risk of neonatal seizures demonstrated that background abnormalities on the
      initial EEG were strongly associated with electrographic seizures in the
      subsequent 18-24 h. To test this association prospectively, we examined the
      relationship between EEG background and the presence of electrographic seizures
      in the next 22 at-risk infants monitored for seizures. METHODS: A standard EEG
      was recorded for each infant at risk for seizures. Based on specific criteria,
      the background was graded as normal; immature for age; or mildly, moderately, or
      severely abnormal. The EEG was then monitored continuously until no
      electrographic seizures were recorded for 18-24 h. RESULTS: Findings in the
      retrospective group of 29 infants and the prospective group of 22 infants did not
      differ. For the combined 51 infants, a normal or immature initial EEG background
      predicted the absence of seizures in the subsequent 18-24 h with a sensitivity of
      96% [confidence interval (CI) 0.88, 1.0] and specificity of 81% (CI 0.67, 0.96).
      Administration of antiepileptic drugs (AEDs) before the start of the EEG
      recording did not affect this association. CONCLUSIONS: In 51 consecutively
      monitored infants at risk for neonatal seizures, a normal or immature EEG
      background strongly predicted the absence of electrographic seizures in the
      subsequent 18-24 h; background abnormalities strongly predicted the occurrence of
      electrographic seizures concomitantly or in the subsequent 18-24 h of recording.
      Screening infants at risk for neonatal seizures with a routine EEG allows
      identification of infants at highest risk for seizures, thus conserving resources
      required for continuous EEG monitoring and facilitating early intervention for
      seizures.

PMID- 9596210
TI  - Fritz E. Dreifuss 1926-1997.

PMID- 9596211
TI  - Arthur Allen Ward, Jr., M.D. 1916-1997.

PMID- 9596212
TI  - Modifications of airway reconstruction in children.
AB  - We review our treatment experience of subglottic stenosis in 66 children. Sixty
      one of these children required some form of airway expansion using cartilage
      grafts. Eight children had grade I (Cotton classification), 15 grade II, 28 grade
      III, and 15 grade IV stenosis. All patients with grade I and II lesions were
      decannulated. Ninety-three percent of grade III patients and 67% of grade IV
      patients were also ultimately decannulated. Laryngotracheal reconstruction with
      costal cartilage grafting has become widely accepted for treatment of severe
      laryngotracheal stenosis. Several modifications of this technique have been
      employed to treat our patients. Recently, we have used a modified single-stage
      technique with an endotracheal tube stent, externally secured for 1 week, to
      avoid postoperative intensive care unit admission for sedation and/or paralysis,
      and its related complications. Posterior graft design and placement without
      sutures was also performed in 20 cases. A two-surgeon technique that involves a
      simultaneous endoscopic control of incision of the stenotic area was employed.
      These modifications will be described in detail.

PMID- 9596213
TI  - Neuromuscular organization of the human upper esophageal sphincter.
AB  - The upper esophageal sphincter (UES) is a key component of swallowing, and yet,
      its anatomy and function are still incompletely understood. The UES is a
      functional entity that is composed of three muscles: the cricopharyngeal (CP)
      muscle, the inferior pharyngeal constrictor (IPC) muscle, and the upper
      esophageal (UE) muscle. This study compared the anatomy of the three muscles of
      the UES in nine human autopsy specimens. The variables examined included the
      pattern of motor end plates (acetylcholinesterase stain), the proportion of fast-
      and slow-twitch muscle fibers (myofibrillar adenosinetriphosphatase), and the
      details of their nerve supply (Sihler's stain). The results demonstrated that
      each variable is different in the three muscles. For example, the IPC muscle is
      innervated by the pharyngeal plexus, the CP muscle by both the pharyngeal plexus
      and the recurrent laryngeal nerve (RLN), and the UE muscle by the RLN. The IPC
      and CP muscles showed distinct motor end plate bands, while the horizontal part
      of the CP muscle also contained small and randomly scattered end plates. This
      latter pattern was present throughout the UE muscle. Analysis of the muscle fiber
      types of the UES revealed a type I (slow) predominance (89%) in the CP and UE
      muscles and a type II (fast) predominance (62%) in the IPC muscle. However, the
      IPC muscle is composed of two layers: a fast, thick, outer layer (90% type II)
      and a slow, thin, inner layer (85% type I). The implications of these findings
      for the diagnosis and treatment of UES dysfunction will be discussed.

PMID- 9596215
TI  - "Exploratory" surgery for advanced carcinoma of the larynx: a relatively safe
      approach.
AB  - Between the years 1970 and 1986, the author managed 132 patients with T3 glottic
      carcinoma. Over half of these patients were explored in an effort to safely
      perform subtotal laryngectomy. Twenty-seven of them were found to have extension
      of tumor that required immediate conversion to total laryngectomy. Five-year
      survival rates were essentially the same for all three groups: immediate total
      laryngectomy, subtotal laryngectomy, and total laryngectomy following attempted
      subtotal laryngectomy. I conclude that carefully selected patients with T3
      glottic cancer may be candidates for subtotal laryngectomy after surgical
      exploration, since conversion to total laryngectomy yields local control rates as
      satisfactory as those of initial total laryngectomy. When subtotal laryngectomy
      is possible, local control of tumor and recurrence rates are as satisfactory as
      those of total laryngectomy.

PMID- 9596214
TI  - FEESST: a new bedside endoscopic test of the motor and sensory components of
      swallowing.
AB  - We here introduce an office or bedside method of evaluating both the motor and
      sensory components of swallowing, called fiberoptic endoscopic evaluation of
      swallowing with sensory testing (FEESST). FEESST combines the established
      endoscopic evaluation of swallowing with a technique that determines
      laryngopharyngeal (LP) sensory discrimination thresholds by endoscopically
      delivering air pulse stimuli to the mucosa innervated by the superior laryngeal
      nerve. Endoscopic assessment of LP sensory capacity followed by endoscopic
      visualization of deglutition was prospectively performed 148 times on 133
      patients with dysphagia over an 8-month period. The patients had a variety of
      underlying diagnoses, with stroke and chronic neurologic disease predominating (n
      = 94). Subsequent to LP sensory testing, a complete dysphagia evaluation was
      conducted. Various food and liquid consistencies were dyed green, and attention
      was paid to their management throughout the pharyngeal stage of swallowing.
      Evidence of latent swallow initiation, pharyngeal pooling and/or residue,
      laryngeal penetration, laryngeal aspiration, and/or reflux was noted.
      Recommendations for therapeutic intervention were based on information obtained
      during the FEESST and often involved the employment of compensatory swallowing
      strategies, modification of the diet or its presentation, placement on non-oral
      feeding status, and/or referral to other related specialists. All patients
      successfully completed the examination. In 111 of the evaluations (75%), severe
      (>6.0 mm Hg air pulse pressure [APP]) unilateral or bilateral LP sensory deficits
      were found. With puree consistencies, 31% of evaluations with severe deficits,
      compared to 5% of evaluations with either normal sensitivity or moderate (4.0 to
      6.0 mm Hg APP) LP sensory deficits, displayed aspiration (p < .001, chi2 test).
      With puree consistencies, 69% of evaluations with severe deficits, compared to
      24% with normal or moderate deficits, displayed laryngeal penetration (p < .001,
      chi2 test). FEESST allows the clinician to obtain a comprehensive bedside
      assessment of swallowing that is performed as the initial swallowing evaluation
      for the patient with dysphagia.

PMID- 9596216
TI  - Verrucous carcinoma of the larynx.
AB  - Verrucous carcinoma is a well-differentiated squamous cell carcinoma with minimal
      cytologic atypia. Characteristically, the surface shows papillary fronds with
      prominent hyperkeratosis. Its benign appearance makes diagnosis difficult and
      often delays treatment. This is a review of 52 histologically confirmed cases of
      verrucous carcinoma of the larynx treated at the Mayo Clinic between 1960 and
      1987. The follow-up ranged from 2 to 304 months. The most common primary
      treatment modality was surgery. Two patients died of laryngeal cancer. In both
      cases, the recurrence was a high-grade carcinoma histologically distinct from the
      original verrucous carcinoma. The T stage, clinical stage, and type of surgical
      excision failed to predict survival. The presence of extensive leukoplakia
      surrounding the exophytic tumor approached statistical significance (p = .08) in
      predicting recurrence. Four patients were treated with radiotherapy--in each, to
      control residual disease. One of these patients developed a local recurrence.
      None of the irradiated tumors in this series showed anaplastic dedifferentiation,
      and none of the irradiated patients died of uncontrolled local or regional
      disease. We conclude that verrucous carcinoma of the larynx should be treated by
      conservative surgical resection when possible. Radiotherapy can be effectively
      used for disease that cannot be resected with preservation of laryngeal function.
      Total laryngectomy should be reserved for recurrent disease or the rare case of
      anaplastic transformation.

PMID- 9596217
TI  - Assessment of two objective voice function indices.
AB  - In the care of patients with voice disorders, physicians, speech pathologists,
      and other health care professionals routinely make diagnoses, recommend
      treatment, and evaluate outcomes. Although objective and subjective measures
      exist, unfortunately, there is no widely accepted, valid method for classifying
      voice disorders and assessing outcome after voice treatment. In the present
      research, the relationship between two previously created multivariate objective
      voice function indices, the weighted odds ratio index and the multivariate
      logistic regression index, and subjective assessment of voice function was
      evaluated. Twenty-three adult patients presenting to a speech science laboratory
      for evaluation of voice disorders were studied in this prospective observational
      study together with 12 normal volunteers as controls. Vocal function was measured
      on 14 different parameters with a protocol that included a multichannel input for
      simultaneous assessment of acoustic and physiological parameters. Each patient
      was recorded reading the standard passage "The North Wind and the Sun," and
      recordings were then evaluated by the GRBAS scale. Overall, there was a
      statistically significant relationship between the weighted odds ratio index and
      multivariate logistic regression index and mean GRBAS scores. This research
      demonstrates that the voice function values calculated from two different
      multivariate objective voice function indices are significantly associated with
      subjective voice assessments. These multivariate objective voice indices may be
      appropriate for use in clinical trials and outcomes research on treatment
      effectiveness for voice disorders.

PMID- 9596218
TI  - Visual-induced postural sway in children with and without otitis media.
AB  - Children with otitis media with effusion (OME) have been shown to have a
      significantly higher velocity of sway than normal children. To further evaluate
      the effect of OME on balance, we studied visual dependency for balance by
      investigating the influence of optic flow on postural sway. The results of this
      preliminary study suggest that children with OME may be more visually dependent
      for balance than healthy age-matched controls. This was particularly evident for
      higher-frequency stimulus conditions (0.25 Hz) as opposed to lower-frequency
      stimulus conditions (0.10 Hz). These findings indicate that OME may affect
      vestibular function in children, thereby causing excessive reliance on other,
      nonvestibular sensory cues to maintain balance. Further studies are needed to
      define the role of vestibular function in the management of children with OME.

PMID- 9596219
TI  - Point prevalence of secretory otitis media in children in southern Vietnam.
AB  - Few reliable data exist on the prevalence of secretory otitis media (SOM) in the
      Third World. A large epidemiologic cross-sectional study was undertaken in two
      communes in southern Vietnam to study an urban and a rural community during two
      different climatic conditions: the dry and rainy seasons. The participants
      included 3,300 children (6,598 ears) ages 6 months to 10 years. Otolaryngological
      and medical histories were obtained, and an otolaryngological examination was
      carried out on 1,669 children in April 1995 (the dry season) and on 1,631
      children in December 1995 (the rainy season). Tympanograms were obtained (n =
      6,055), 429 of which were type B curves. The overall prevalence of SOM was 7.1%,
      the highest incidence was at the age of 2 years (with a prevalence of 22%), and
      there was a significantly higher prevalence of SOM during the rainy season than
      during the dry season. No significant difference in incidence was found in the
      urban district as compared to the rural district.

PMID- 9596220
TI  - Site of cortical utricular representation with special reference to the
      somatosensory barrel field in the gerbil.
AB  - In mammals, the osseous semicircular canals of the vestibular labyrinths are
      usually embedded in the pyramis of the temporal bone. Thus, the osseous
      semicircular canals are a cavity system that can only be visualized by injection
      molding. Exceptionally, the walls of the osseous semicircular canals of the
      Mongolian gerbil are not embedded, but exposed in the hollow space in the
      temporal bone. Under urethane anesthesia, a window was made in the periotic
      capsule of the gerbil to reach this hollow space (semicircular canal triangle),
      and a pair of wire electrodes were inserted through an opening made in the
      horizontal semicircular canal toward the utricular nerve endings. Repetitive
      electric stimuli at 80 Hz were applied, and the direction of eye movements was
      noted. Subsequently, the stimulation frequency was reduced to 0.3 Hz, and evoked
      potentials were recorded from the neocortex. Positive surface potentials and
      negative deep potentials were recorded in the somatosensory area and, more
      specifically, in the vibrissa "barrel field," as judged by later histochemical
      staining of the cortical specimens. This unique anatomic feature of the gerbil
      labyrinth offers an opportunity whereby the vestibular organ can be reached
      without any heavy surgical insult, and the presence of fine-grain vibrissa
      barrels in this species (seven rows instead of five rows in most rodents) will
      help elucidate functional interactions between vestibular and somatosensory
      sensations.

PMID- 9596221
TI  - Characterization of the eosinophil chemokine RANTES in nasal polyps.
AB  - Previous studies have demonstrated that the cytokine RANTES (Regulated And Normal
      T cell Expressed and Secreted) has been shown to be a potent mediator of
      eosinophil chemotaxis in vitro and of leukocyte recruitment. Because eosinophils
      are the hallmark cells in nasal polyposis, we hypothesize that RANTES is locally
      produced within the nasal polyp microenvironment and is responsible for the
      eosinophil recruitment seen in nasal polyposis. To begin to test this hypothesis,
      we evaluated nasal polyps from 17 patients and 3 control specimens for
      distribution and content of RANTES using immunohistochemical techniques and
      enzyme-linked immunosorbent assay technology. Our immunohistochemical studies
      demonstrated that in nasal polyposis, RANTES antigen staining occurred
      predominantly within eosinophils and epithelial cells. To quantify the relative
      levels of RANTES in normal and nasal polyp specimens, tissue homogenates were
      prepared, quantified, and normalized to protein levels. We detected RANTES in all
      17 nasal polyp tissue homogenates (566 +/- 16 pg/mg total protein). The RANTES
      levels in nasal polyp homogenates were nearly 40-fold higher than the RANTES
      levels in normal tissue (15.7 +/- 28.2 pg/mg total protein). Thus, it appears
      that increased expression of RANTES by eosinophils and epithelial cells within
      the nasal polyp microenvironment promotes eosinophil recruitment and activation
      within nasal polyps. We hypothesize that RANTES induces increased recruitment and
      activation of eosinophils, presumably contributing to the increased tissue
      changes associated with nasal polyposis.

PMID- 9596222
TI  - Increased density of olfactory receptor neurons immunoreactive for apolipoprotein
      E in patients with Alzheimer's disease.
AB  - Immunolocalization of apolipoprotein E (apoE) was investigated in human olfactory
      mucosa in which olfactory receptor neurons (ORNs) were identified with antiserum
      to protein gene product (PGP) 9.5. Tissue was obtained at autopsy from 10
      nondemented middle-aged or elderly subjects and 9 patients with Alzheimer's
      disease (AD). Double-labeling immunofluorescence established that apoE
      immunoreactivity was colocalized in a subpopulation of PGP 9.5-immunoreactive
      ORNs. The mean number of apoE-immunoreactive ORNs per unit epithelial length in
      AD patients was about 3.5 times greater than that in nondemented patients,
      although the mean number of PGP 9.5-immunoreactive ORNs was similar. The apoE
      immunopositive Schwann cells in olfactory nerve bundles were the probable source
      of apoE in the ORNs. The increased numbers of apoE-immunoreactive ORNs in AD
      patients compared to nondemented subjects demonstrates another manifestation of
      AD-related neuropathology, in addition to cytoskeletal changes, beta-amyloid
      deposition, and changes in immunoreactivity for other neuroproteins, that
      parallels changes in neurons in the AD brain.

PMID- 9596223
TI  - Medialization laryngoplasty with expanded polytetrafluoroethylene. Surgical
      technique and preliminary results.
AB  - Symptomatic unilateral laryngeal paralysis may be treated successfully by a wide
      variety of surgical techniques. These techniques share the concept that
      stabilization of the paralyzed vocal fold in a median position will improve
      glottic function. Medialization laryngoplasty with expanded
      polytetrafluoroethylene (ePTFE) incorporates the general principles of
      established medialization procedures, yet is unique in its simplicity. The
      technique does not require special instrumentation, employs incremental
      adjustment of vocal fold position, and utilizes an implantable material with a
      long history of patient safety. We describe this new technique and report on the
      outcome of our first 16 patients treated. No surgical or implant-related
      complications have occurred. Voice results were measured from preoperative and
      postoperative video and voice recordings by four independent observers using a
      standardized assessment tool. Voice grade and breathiness were evaluated on a
      four-point scale (0 = normal and 3 = abnormal, extreme). The mean overall grade
      improved from 2.3 +/- 0.6 to 1.1 +/- 0.6, and breathiness from 2.0 +/- 0.8 to 0.4
      +/- 0.4. The technique is simple, the implant material has been in clinical use
      for decades, and the voice results are good to excellent.

PMID- 9596224
TI  - Frontoethmoid mucocele complicating Graves' ophthalmopathy.

PMID- 9596225
TI  - Spindle cell carcinoma of the larynx.

PMID- 9596226
TI  - Wegener's granulomatosis of the head and neck.
AB  - Among the more puzzling non-neoplastic necrotizing lesions of the head and neck
      area is Wegener's granulomatosis. This is a condition of unknown cause that may
      present (in the head and neck area) with ulceration of the nasal septum, sinus
      mucosa, oral mucosa, or external ear canal, or even destruction of the vocal
      cord. Diagnosis depends on the pathologic finding of a characteristic
      inflammatory reaction pattern (which, in its best-developed form, includes
      necrosis, granulomatous inflammation, and vasculitis) and the serum finding of an
      elevated antinuclear cytoplasmic antigen. Treatment is principally medical, with
      the use of powerful immunosuppressive agents. Distinction from other conditions
      that may mimic Wegener's granulomatosis (such as malignant lymphoma and
      infections) is of critical importance in constructing an appropriate treatment
      strategy.

PMID- 9596227
TI  - Role of flexible laryngoscopy for evaluating aspiration.

PMID- 9596228
TI  - Perilymphatic fistula: a Washington, DC experience (Ann Otol Rhinol Laryngol
      1997;106:830-7)

PMID- 9596229
TI  - Aspirin and stroke.

PMID- 9596231
TI  - Stroke unit treatment improves long-term quality of life: a randomized controlled
      trial.
AB  - BACKGROUND AND PURPOSE: We have previously shown that treatment of acute stroke
      patients in the combined acute and rehabilitation stroke unit in our hospital
      improves survival and functional outcome compared with treatment in general
      wards. The primary aim of the present trial was to examine whether the treatment
      in our stroke unit had an effect on different aspects of quality of life (QoL)
      for stroke patients 5 years after the onset of stroke. METHODS: In a randomized
      controlled trial, 110 patients with symptoms and signs of an acute stroke were
      allocated to the stroke unit and 110 to general wards. No significant differences
      existed in baseline characteristics between the two groups. The patients alive
      after 5 years were assessed by the Nottingham Health Profile (NHP) and the
      Frenchay Activities Index (FAI), which were the scales used as primary outcome
      measures for QoL. As secondary outcome measures we used a global score for the
      NHP and a simple visual analogue scale (VAS). RESULTS: After 5 years, 45 of the
      patients treated in the stroke unit and 32 of those treated in general wards were
      alive. All surviving patients were assessed by the FAI. Thirty-seven (82.2%) of
      the stroke unit patients and 25 (78.1%) of the general wards patients were
      assessed by the NHP; 38 (84.4%) and 28 (87.5%), respectively, were assessed by
      the VAS. Patients treated in the stroke unit had a higher score on the FAI
      (P=0.0142). Assessment with the NHP showed better results in the stroke unit
      group for the dimensions of energy (P=0.0323), physical mobility (P=0.0415),
      emotional reactions (P=0.0290), social isolation (P=0.0089), and sleep
      (P=0.0436), although there was no difference in pain (P=0.3186). The global NHP
      score and VAS score also showed significantly better results in the stroke unit
      group (NHP, P<0.01; VAS, P<0.001). Patients who were independent in activities of
      daily living had significantly better QoL assessed by these scales than patients
      who were dependent. CONCLUSIONS: Our study shows for the first time that stroke
      unit care improves different aspects of long-term QoL for stroke patients.

PMID- 9596230
TI  - Aspirin use and incident stroke in the cardiovascular health study. CHS
      Collaborative Research Group.
AB  - BACKGROUND AND PURPOSE: Randomized clinical trials testing aspirin in relatively
      low-risk, middle-aged people have consistently shown small increases in stroke
      associated with aspirin use. We analyzed the relationship between the regular use
      of aspirin and incident ischemic and hemorrhagic stroke among people aged 65
      years or older participating in the Cardiovascular Health Study. METHODS: We
      conducted a multivariate analysis of incident stroke rates in a prospectively
      assessed, observational cohort of 5011 elderly people followed for a mean of 4.2
      years. RESULTS: Participants had a mean age of 72 years, and 58% were women.
      Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently
      at study entry. Frequent aspirin use was associated with an increased rate of
      ischemic stroke compared with nonusers (relative risk= 1.6; 95% confidence
      interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk
      factors, women who used aspirin frequently or infrequently at study entry had a
      1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of
      ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers.
      In men, aspirin use was not statistically significantly associated with stroke
      risk. Findings were similar when aspirin use in the years before the incident
      stroke was used in the modeling. Aspirin use at entry was also associated with a
      4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both
      infrequent and frequent users of aspirin (P=0.003). CONCLUSIONS: Aspirin use was
      associated with increased risks of ischemic stroke in women and hemorrhagic
      stroke overall in this elderly cohort, after adjustment for other stroke
      predictors. The possibility exists of confounding by reasons for aspirin use
      rather than cause and effect. Whether regular aspirin use increases stroke risk
      for elderly people without cardiovascular disease can only be determined by
      randomized clinical trials.

PMID- 9596232
TI  - Alcohol consumption and atherosclerosis: what is the relation? Prospective
      results from the Bruneck Study.
AB  - BACKGROUND AND PURPOSE: Potential effects of regular alcohol consumption on
      atherogenesis are still controversial mainly due to the lack of prospective
      population-based studies. METHODS: The Bruneck Study is a prospective population
      based survey of atherosclerosis and its risk factors. The study population
      comprises a sex- and age-stratified random sample of men and women aged 40 to 79
      years. Participation and follow-up were more than 90% complete. Changes in
      carotid atherosclerosis between the 1990 baseline and the first follow-up in 1995
      were monitored by high-resolution duplex ultrasonography. Alcohol intake was
      quantified with a standardized questionnaire and prospective diet records.
      RESULTS: Alcohol consumption less than once a week (occasional drinking) had no
      effect on atherogenesis. The association between regular alcohol intake and
      incident carotid atherosclerosis (early atherogenesis) was J-shaped, with light
      drinkers facing a lower risk than either heavy drinkers or abstainers. Protection
      offered by alcohol consumption of <50 g/d appeared to act through inhibition of
      the injurious action of high levels of low-density lipoprotein (LDL) cholesterol.
      Excess risk of incident atherosclerosis observed among heavy alcohol consumers (>
      or =100 g/d) clearly surpassed the risk burden afforded by heavy smoking. The
      association between regular alcohol intake and incident carotid stenosis
      (advanced atherogenesis) was U-shaped. Odds ratios were generally shifted toward
      protection and did not rely on LDL cholesterol levels. We failed to find any
      differential effects of alcohol from various sources. All associations remained
      independently significant when we adjusted for lifestyle, coincidental smoking,
      and the metabolic complex associated with drinking. CONCLUSIONS: Our findings
      support the view that adverse and beneficial effects of alcohol on arterial
      disease are mediated in part by a dose-dependent promotion or deceleration of
      atherogenesis. The protection afforded by light drinking may possibly be
      attributed to antithrombotic effects and inhibition of the atherogenic action of
      high levels of LDL cholesterol.

PMID- 9596233
TI  - Cigarette smoking as a determinant of high-grade carotid artery stenosis in
      Hispanic, black, and white patients with stroke or transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: We sought to investigate the association of cigarette
      smoking with high-grade carotid artery stenosis in Hispanic, black, and white
      patients with cerebral ischemia in two independent samples. METHODS:
      Prospectively collected data from the Northern Manhattan Stroke Study (NOMASS)
      (n=431) and the Berlin Cerebral Ischemia Databank (BCID) (n=483) were used
      separately for a cross-sectional study estimating the association between
      cigarette smoking and high-grade carotid stenosis (defined as a luminal narrowing
      of > or =60%, diagnosed by duplex and/or Doppler ultrasound). In both studies,
      cerebral ischemia patients with normal sonographic findings or nonstenosing
      plaques of their carotid arteries served as a comparison group. Multivariate
      logistic regression models were used for statistical tests to determine the
      association between smoking and the dependent variable for high-grade carotid
      stenosis. Age, sex, hypertension, diabetes, hypercholesterolemia, and
      race/ethnicity were considered potential confounders. Further analyses of the
      NOMASS data estimated the effect of the amount of cigarette use and the impact of
      race/ethnicity. RESULTS: High-grade carotid stenoses were found in 14% of the
      NOMASS and in 21% of the Berlin patients. In Berlin the entire sample was white,
      whereas in New York only 19% of the cohort were white. In both samples, smoking
      was independently associated with severe carotid stenosis (NOMASS: odds ratio
      [OR], 1.5; 95% confidence interval [CI], 1.1 to 2.0; BCID: OR, 3.9; 95% CI, 2.4
      to 6.4). Patients smoking 20 pack-years or more showed a significant association
      (OR, 2.0; 95% CI, 1.1 to 3.9), whereas no significant effect was found for lower
      amounts of cigarette use. In NOMASS, white smokers displayed a significant (OR,
      3.2; 95% CI, 1.1 to 8.9) association with high-grade carotid stenosis, the
      association for black smokers was less strong, and no association was found among
      Hispanics. CONCLUSIONS: Smoking is an independent determinant of severe carotid
      artery stenosis in patients with focal cerebral ischemia. The association differs
      by race/ethnicity, with the greatest effect observed among whites.

PMID- 9596234
TI  - Cigarette smoking and other risk factors for silent cerebral infarction in the
      general population.
AB  - BACKGROUND AND PURPOSE: Silent cerebral infarctions (SCIs) have a prevalence
      between 10% and 40% in the transient ischemic attack population and have been
      associated with increased mortality and morbidity; however, little is known about
      the prevalence and risk factors for SCI in the general population. This report
      focuses on the role of cigarette smoking and other risk factors for SCI in the
      general population. METHODS: MRI scans were performed on 1737 participants
      selected from the general population as part of the Atherosclerosis Risk in
      Communities Study. Smoking status and other major cerebrovascular risk factors
      were assessed, and associations between smoking status and SCIs were established
      with the use of ANCOVA. RESULTS: Overall, the prevalence of SCI in this
      population aged 55 to 70 years was 11%. Cigarette smoking had an ordered
      association (P=0.029) with the presence of SCI, with the odds ratio (OR) of
      nonsmoking participants exposed to environmental tobacco smoke being 1.06 (95%
      confidence interval [CI], 0.64 to 1.75) times as great as for nonsmokers not
      exposed; the OR of past smokers was 1.16 (95% CI, 0.74 to 1.83) times greater,
      and the OR of current smokers was 1.88 (95% CI, 1.13 to 3.13) times greater. An
      increased prevalence was also noted among black, older, and hypertensive
      participants. CONCLUSIONS: This report is among the first to examine the risk
      factors for SCI in the general population and finds a relatively high overall
      prevalence (11%). There is an ordered relationship between increasing exposure to
      cigarette smoke and the presence of SCI that parallels the relationship between
      smoking and carotid atherosclerosis. The magnitude of the association with
      smoking is substantial compared with the effect of hypertension and other
      traditional cerebrovascular risk factors. The reduction in prevalence of SCI
      between current and past smokers and the trend that increased pack-years of
      smoking is related to increased prevalence of SCI are both additional arguments
      for smoking avoidance and cessation.

PMID- 9596235
TI  - Dose optimization of intravenous magnesium sulfate after acute stroke.
AB  - BACKGROUND AND PURPOSE: Parenterally administered MgSO4 is neuroprotective in
      standard animal models of focal cerebral ischemia and in many other paradigms of
      brain injury. Previous small clinical trials in stroke patients have explored the
      safety and tolerability of different infusion regimens. This study was undertaken
      to optimize the regimen for a multicenter trial. METHODS: Within 24 hours of the
      onset of clinically diagnosed stroke, patients were randomized to receive placebo
      or one of three intravenous MgSO4 infusions: a loading infusion of 8, 12, or 16
      mmol, followed by 65 mmol over 24 hours. Cardiovascular parameters, serum
      magnesium concentrations, and blood glucose concentrations were determined.
      Outcome at 30 and 90 days was recorded. RESULTS: Twenty-five patients were
      recruited and treated at a mean time of 20 hours after stroke. No tolerability
      problems were identified. No effects of magnesium on heart rate, blood pressure,
      or blood glucose were evident. Serum magnesium concentrations rose to target
      levels most rapidly in the highest loading infusion group and were maintained in
      all groups for at least 24 hours. CONCLUSIONS: MgSO4 infusions that rapidly
      elevate the serum magnesium concentration to potentially therapeutic levels are
      well tolerated and have no major hemodynamic effects in patients with acute
      stroke. The 16-mmol loading infusion achieved target serum concentrations most
      rapidly and has been chosen for further trials.

PMID- 9596236
TI  - Impact of medical treatment on the outcome of patients after aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: The rationale behind early aneurysm surgery in patients
      with subarachnoid hemorrhage (SAH) is the prevention of rebleeding as early as
      possible after SAH. In addition, by clipping the aneurysm as early as possible,
      one can apply treatment for cerebral ischemia more vigorously (induced
      hypertension) without the risk of rebleeding. Hypervolemic hemodilution is now a
      well-accepted treatment for delayed cerebral ischemia. We compared the
      prospectively collected clinical data and outcome of patients admitted to the
      intensive care unit in the period 1977 to 1982 with those of patients admitted in
      the period 1989 to 1992 to measure the effect of the change in medical management
      procedures on patients admitted in our hospital with SAH. METHODS: We studied 348
      patients admitted within 72 hours after aneurysmal SAH. Patients with negative
      angiography results and those in whom death appeared imminent on admission were
      excluded. The first group (group A) consisted of 176 consecutive patients
      admitted from 1977 through 1982. Maximum daily fluid intake was 1.5 to 2 L.
      Hyponatremia was treated with fluid restriction (<1 L/24 h). Antihypertensive
      treatment with diuretic agents was given if diastolic blood pressure was >110 mm
      Hg. Patients in the second group (172 consecutive patients; group B) were
      admitted from 1989 through 1992. Daily fluid intake was at least 3 L, unless
      cardiac failure occurred. Diuretic agents and antihypertensive medications were
      avoided. Cerebral ischemia was treated with vigorous plasma volume expansion
      under intermittent monitoring of pulmonary wedge pressure, cardiac output, and
      arterial blood pressure, aiming for a hematocrit of 0.29 to 0.33. Aneurysm
      surgery was planned for day 12. RESULTS: Patients admitted in group B had less
      favorable characteristics for the development of cerebral ischemia and for good
      outcome when compared with patients in group A. Despite this, we found a
      significant decrease in the frequency of delayed cerebral ischemia in patients of
      group B treated with tranexamic acid (P=0.00005 by log rank test) and
      significantly improved outcomes among patients with delayed cerebral ischemia
      (P=0.006 by chi2 test) and among patients with deterioration from hydrocephalus
      (P=0.001 by chi2 test). This resulted in a significant improvement of the overall
      outcome of patients in group B when compared with those in group A (P=0.006 by
      chi2 test). The major cause of death in group B was rebleeding (P=0.011 by chi2
      test). CONCLUSIONS: We conclude that the outcome in our patients with aneurysmal
      SAH was improved but that rebleeding remains a major cause of death. Patient
      outcome can be further improved if we can increase the efficacy of preventive
      measures against rebleeding by performing early aneurysm surgery.

PMID- 9596237
TI  - Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous
      malformation.
AB  - BACKGROUND AND PURPOSE: Decisions on invasive arteriovenous malformation (AVM)
      treatment are currently based on natural-course risk estimates of AVM bleeding
      and assumptions on morbidity from cerebral hemorrhage in general. However,
      morbidity of AVM hemorrhage has rarely been reported. We sought to assess the
      morbidity of intracranial hemorrhage in patients with cerebral AVMs. METHODS:
      From a prospective AVM database, 119 patients were analyzed: 115 had a hemorrhage
      as the diagnostic event, and 27 of them suffered a second hemorrhage during
      follow-up; an additional 4 patients had other diagnostic symptoms but bled during
      follow-up. The type (parenchymal, subarachnoid, intraventricular) and location of
      AVM hemorrhage were determined by CT/MR brain imaging. Disability and
      neurological impairment were assessed with the Barthel Index, the Rankin Scale,
      and the National Institutes of Health Stroke Scale, with a mean follow-up time of
      16.2 months. RESULTS: Of the 115 incident hemorrhages, 34 (30%) were
      subarachnoid, 27 (23%) parenchymal, 18 (16%) intraventricular, and 36 (31%) in
      combined locations. In 54 patients (47%; 95% confidence interval [CI], 38% to
      56%) the incident hemorrhage resulted in no neurological deficit, and an
      additional 43 patients (37%; 95% CI, 28% to 46%) were independent in their daily
      activities (Rankin 1). Fifteen patients (13%; 95% CI, 7% to 19%) were moderately
      disabled (Rankin 2 or 3), and 3 (3%; 95% CI, 0% to 6%) were severely disabled
      (Rankin > or =4). Parenchymal hemorrhages were most likely to result in a
      neurological deficit (52%). Type and morbidity of hemorrhage during follow-up
      were similar to incident events. Twenty (74%) of 27 patients with both incident
      and follow-up hemorrhages were normal or independent (Rankin 0 or 1). None of the
      patients with a hemorrhage during follow-up died during the observation period.
      CONCLUSIONS: Hemorrhage from cerebral AVMs appears to have a lower morbidity than
      currently assumed. This finding encourages a reevaluation of the risks and
      benefits of invasive AVM treatment.

PMID- 9596238
TI  - Role of CT angiography in patient selection for thrombolytic therapy in acute
      hemispheric stroke.
AB  - BACKGROUND AND PURPOSE: It has been shown that thrombolytic therapy can improve
      clinical outcome in a subgroup of patients with acute cerebral ischemia. This
      subgroup was characterized by certain clinical and imaging findings (eg, moderate
      to severe neurological deficit for less than 3 to 6 hours, occlusion of the
      middle cerebral artery, lack of extended infarct signs on CT, and efficient
      leptomeningeal collaterals). Although not part of published prospective
      randomized rtPA trials, information about the status of the brain vessels would
      be helpful in the selection of patients who may benefit the most. Our purpose was
      to determine the feasibility of CT angiography (CTA) in patients with acute
      hemispheric ischemia and to evaluate its relevance for thrombolytic therapy.
      METHODS: CTA was performed in 40 consecutive patients (11 women and 29 men; age
      range, 19 to 80 years) with moderate or severe symptoms (National Institutes of
      Health Stroke Scale score of > or =8) of acute hemispheric ischemia. CTA findings
      were compared with Doppler ultrasonography (US; n=22) and intra-arterial digital
      subtraction angiography (DSA; n=7). Twenty patients received thrombolytic
      therapy, the remaining patients received intravenous heparin. RESULTS: Images and
      3-dimensional reconstructions of diagnostic quality could be obtained in all
      patients. Thirty-four patients had a vessel occlusion. The extent of
      leptomeningeal collaterals correlated significantly with the outcome after
      thrombolytic therapy (rs=0.46, P<0.05). The evaluation of diagnostic accuracy
      showed a high agreement with US (22 of 22) and DSA (6 of 7). CONCLUSIONS: CTA can
      provide important information for the initiation of therapy in patients with
      acute hemispheric ischemia. Identification of patients with autolyzed thrombi,
      occlusion of the internal carotid artery bifurcation, and poor leptomeningeal
      collaterals is feasible with the use of CTA. These patients may have little
      potential for benefit from thrombolytic therapy.

PMID- 9596239
TI  - Regional ischemia and ischemic injury in patients with acute middle cerebral
      artery stroke as defined by early diffusion-weighted and perfusion-weighted MRI.
AB  - BACKGROUND AND PURPOSE: We sought to map early regional ischemia and infarction
      in patients with middle cerebral artery (MCA) stroke and compare them with final
      infarct size using advanced MRI techniques. MRI can now delineate very early
      infarction by diffusion-weighted imaging (DWI) and abnormal tissue perfusion by
      perfusion-weighted imaging (PWI). METHODS: Seventeen patients seen within 12
      hours of onset of MCA stroke had MR angiography, standard MRI, and PWI and DWI
      MRI. PWI maps were generated by analysis of the passage of intravenous contrast
      bolus through the brain. Cerebral blood volume (CBV) was determined after
      quantitative analysis of PWI data. Volumes of the initial DWI and PWI lesion were
      calculated and compared with a final infarct volume from a follow-up imaging
      study (CT scan or MRI). RESULTS: Group 1 (10 patients) had MCA stem (M1)
      occlusion by MR angiography. DWI lesion volumes were smaller than the volumes of
      CBV abnormality. In 7 patients the final stroke volume was larger or the same,
      and in 3 it was smaller than the initial CBV lesion. Group 2 (7 patients) had an
      open M1 on MR angiography with distal MCA stroke. In 6 group 2 patients, the
      initial DWI lesion matched the initial CBV abnormality and the final infarct.
      CONCLUSIONS: Most patients with M1 occlusion showed progression of infarction
      into the region of abnormal perfusion. In contrast, patients with open M1 had
      strokes consistent with distal branch occlusion and had maximal extent of injury
      on DWI at initial presentation. Application of these MRI techniques should
      improve definition of different acute stroke syndromes and facilitate clinical
      decision making.

PMID- 9596240
TI  - Patent foramen ovale size and embolic brain imaging findings among patients with
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Although the cause of stroke among patients with patent
      foramen ovale (PFO) may be due to paradoxical cerebral embolism (PCE), this
      mechanism is often difficult to prove. The aim of our study was to evaluate the
      association between brain imaging findings suggestive of embolism and PFO among
      ischemic stroke patients. METHODS: As part of the Northern Manhattan Stroke
      Study, 95 patients with first ischemic stroke over age 39 underwent
      transesophageal echocardiography (TEE) for evaluation of a cardiac source of
      embolism. The stroke subtype was determined by modified NINDS Stroke Data Bank
      criteria. Stroke subtype and MRI/CT imaging data were evaluated blind to the
      presence of a PFO. These findings were compared between two groups: patients with
      medium to large PFO (> or =2 mm) and small (<2 mm) or no PFO. RESULTS: Of the 95
      patients who underwent TEE, 31 (33%) had a PFO. The frequency of PFO was
      significantly greater among patients with cryptogenic infarcts (19 of 42; 45%)
      compared with patients with determined cause of stroke (12 of 53, 23%; P=0.02).
      Medium to large PFOs were found more often among cryptogenic strokes than among
      infarcts of determined cause (26% versus 6%; P=0.04). Superficial infarcts
      occurred more often in the group with larger PFOs than in the group with small or
      no PFOs (50% versus 21%; P=0.02). Patients with medium or large PFOs more
      frequently had occipital and infratentorial strokes (57% versus 27%; P=0.02).
      CONCLUSIONS: Stroke patients with larger PFOs show more brain imaging features of
      embolic infarcts than those with small PFOs. Larger PFOs may be more likely to
      cause paradoxical embolization and may help explain the stroke mechanism among
      patients with no other definite cause.

PMID- 9596241
TI  - Potential and limitations of echocontrast-enhanced ultrasonography in acute
      stroke patients: a pilot study.
AB  - BACKGROUND AND PURPOSE: Ultrasonography (US) is a well-established method used to
      assess the brain-supplying arteries in the acute stroke setting. However, several
      technical and anatomic limitations are known to reduce its diagnostic accuracy
      and confidence level. Echocontrast agents (ECA) are known to improve the signal
      to-noise ratio by enhancing the intensity of the reflecting Doppler signal. We
      undertook this prospective study to evaluate the diagnostic value of ECA in a
      consecutive, nonselected cohort of acute stroke patients with insufficient native
      US investigations. METHODS: During a 1-year period, 25 patients were examined
      within 48 hours of the onset of stroke. The need for ECA was due to an
      insufficient transtemporal (n=18), transforaminal (n=4), or extracranial (n=3)
      imaging of arteries potentially involved in the ischemic event. In 12 patients, a
      diagnostic suspicion could natively be raised, whereas in the other 13 patients,
      the strongly reduced image quality did not allow for any neurovascular
      conclusions. Four grams of Levovist was injected at a concentration of 200 mg/mL
      and 400 mg/mL for the extracranial and transcranial insonations, respectively.
      The effect of the echocontrast enhancement was assessed with respect to (1)
      signal enhancement, (2) image quality, (3) final diagnostic confidence, and (4)
      the need for additional neurovascular imaging methods. RESULTS: In all but one
      patient (96%), a strong signal enhancement was noted, leading to a moderate
      (n=11) or strong improvement (n=10) of the transcranial image quality. Thus in a
      total of 18 patients (72%), the echoenhancement provided a neurovascular
      diagnosis of sufficient confidence. This led to the confirmation of the
      previously suspected findings and disclosed three further occlusions and four
      stenoses of the intracranial arteries. In contrast, for the three extracranial
      examinations the image quality was not sufficiently improved because of
      persistent color artifacts derived from adjacent neck vessels. Besides the seven
      patients with inconclusive examinations, five patients with conclusive
      echoenhanced US studies (48% in total) demanded additive neurovascular imaging
      studies, based on the clinical decision of the attending physicians. This led to
      confirmation of all high-confident sonographic diagnoses. CONCLUSIONS: In
      summary, in approximately three fourths of our acute stroke patients with
      insufficient native US investigations, echocontrast enhancement enabled a
      reliable neurovascular diagnosis, allowing the cancellation of additive
      neurovascular imaging procedures in half of our cohort. Our preliminary results
      suggest that ECA can reasonably support the early cerebrovascular workup in the
      acute stroke setting.

PMID- 9596242
TI  - Diagnostic impact and prognostic relevance of early contrast-enhanced
      transcranial color-coded duplex sonography in acute stroke.
AB  - BACKGROUND AND PURPOSE: We sought to evaluate the diagnostic value of echo
      enhanced transcranial color-coded duplex sonography (TCCD) and the clinical
      relevance of vascular pathology assessed by sonography for early clinical outcome
      in acute ischemic stroke. METHODS: We present 23 consecutive patients with an
      anterior circulation stroke in whom clinical examination, CT, and ultrasonography
      were performed within 5 hours after the onset of symptoms. Transcranial Doppler
      sonography (TCD) and unenhanced and contrast-enhanced TCCD (Levovist, 4 g, 300
      mg/mL) were compared for their ability to detect middle cerebral artery (MCA)
      occlusion and flow velocity reduction suggesting hemodynamic impairment in the
      MCA distribution pathway. Sonographic examination times were registered. Baseline
      clinical characteristics and CT findings were assessed. Neurological deficit was
      quantified according to the National Institutes of Health Stroke Scale score,
      with an early clinical improvement defined as decrease of the score by 4 or more
      points or a complete resolution of the deficit on day 4. RESULTS: Contrast
      enhanced TCCD enabled diagnosis of intracranial vascular pathology in 20 affected
      hemispheres, whereas unenhanced TCCD and TCD were conclusive in 7 and 14
      hemispheres, respectively (P=0.0001). Contrast-enhanced TCCD was superior in
      evaluating distal carotid (carotid-T) occlusion and differentiating major vessel
      occlusions from patent arteries with flow velocity diminution. Mean examination
      time for enhanced TCCD ranged from 5 to 7 minutes, depending on the number of
      investigated vessels (without or with MCA branches). Logistic regression selected
      a patent MCA without reduced blood flow velocity as the only independent
      predictor for an early clinical improvement (P<0.01). CONCLUSIONS: Contrast
      enhanced TCCD is a promising tool for early prognosis in anterior circulation
      stroke. It is considered superior to unenhanced TCCD and TCD.

PMID- 9596243
TI  - Age and sex differences in cerebral hemodynamics: a transcranial Doppler study.
AB  - BACKGROUND AND PURPOSE: Hemodynamic factors seem to play an important role in the
      pathogenesis of cerebral ischemic events. The aim of this study was to evaluate
      whether changes in cerebrovascular reactivity occur in women after menopause.
      METHODS: Using transcranial Doppler ultrasonography, we studied the changes of
      flow velocity after hypercapnia in the middle cerebral arteries of 45 healthy
      premenopausal women (mean age, 32.3 years; range, 20 to 47 years) and 40
      postmenopausal women (mean age, 54.4 years; range, 48 to 64 years). The same
      measurements were recorded in two groups of healthy male subjects age matched
      with premenopausal (45 subjects) and postmenopausal women (40 subjects).
      Moreover, a subgroup of postmenopausal women aged 48 to 53 years (15 subjects)
      were compared with a group of 15 premenopausal women of the same age. We obtained
      hypercapnia with breath holding and evaluated cerebrovascular reactivity with the
      breath-holding index (BHI). RESULTS: BHI was significantly lower in
      postmenopausal women (0.89+/-0.3) than in premenopausal women (1.59+/-0.3;
      P<0.0001) and in young (1.34+/-0.5; P<0.001) and old men (1.20+/-0.4; P<0.04). In
      the latter group, BHI was significantly lower than in premenopausal women
      (P<.0001). BHI values were also significantly lower in postmenopausal than in
      premenopausal women of the same age (0.81+/-0.1 versus 1.34+/-0.1; P<0.0001).
      CONCLUSIONS: These findings suggest that the large reduction of cerebrovascular
      reactivity in postmenopausal women cannot be considered a simple factor related
      to aging but is probably influenced by hormonal changes. The alteration in
      cerebrovascular regulation could be involved in the increase of cerebrovascular
      disease in postmenopausal women.

PMID- 9596244
TI  - Can cerebrovascular reactivity be assessed without measuring blood pressure in
      patients with carotid artery disease?  .
AB  - BACKGROUND AND PURPOSE: Conventional methods of assessing cerebrovascular
      reactivity (CVR) omit the influence of blood pressure (BP). This study
      demonstrates the significant influence of BP during the assessment of CVR in
      patients with carotid artery disease. METHODS: In 56 subjects the CVR was
      bilaterally assessed by measurement of cerebral blood flow velocity change in
      response to inhalation of 5% CO2 in air while BP was continuously monitored.
      Three methods of calculating the CVR were used: the conventional ratio between
      relative cerebral blood flow velocity and end-tidal CO2, simple linear
      regression, and multiple linear regression analysis (MLRA). The clinical
      significance of the difference in CVR indices was evaluated. The Bland-Altman
      test was applied to quantify the comparability and bias between measurements. The
      magnitude and significance of a change in BP during the CVR assessment were
      calculated in conjunction with an estimate of the velocity change attributed to
      the BP. The statistical significance of the data segment length on the
      variability and magnitude of the CVR index was computed. RESULTS: The value of
      the CVR index was reduced by 20% and 6% in comparison to the conventional ratio
      approach when MLRA and linear regression were applied, respectively. With the use
      of MLRA, in 96% of cases the value of the BP coefficient was statistically
      significant, and in four patients the increase in velocity was primarily
      attributed to the increase in BP. CONCLUSIONS: The influence of BP is significant
      and requires consideration when the CVR index is calculated in patients with
      carotid artery disease.

PMID- 9596245
TI  - Neuromuscular stimulation for upper extremity motor and functional recovery in
      acute hemiplegia.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the efficacy of
      neuromuscular stimulation in enhancing the upper extremity motor and functional
      recovery of acute stroke survivors. METHODS: Forty-six stroke survivors admitted
      to an inpatient rehabilitation unit were randomly assigned to receive either
      neuromuscular stimulation or placebo. Twenty-eight subjects completed the study.
      The treatment group received surface neuromuscular stimulation to produce wrist
      and finger extension exercises. The control group received placebo stimulation
      over the paretic forearm. All subjects were treated 1 hour per day, for a total
      of 15 sessions. Outcomes were assessed in a blinded manner with the upper
      extremity component of the Fugl-Meyer Motor Assessment and the self-care
      component of the Functional Independence Measure at pretreatment, after
      treatment, and at 4 and 12 weeks after treatment. RESULTS: The treatment subjects
      and control subjects had comparable baseline characteristics. Parametric analyses
      revealed significantly greater gains in Fugl-Meyer scores for the treatment group
      after treatment (13.1 versus 6.5; P=0.05), at 4 weeks after treatment (17.9
      versus 9.7; P=0.05), and at 12 weeks after treatment (20.6 versus 11.2; P=0.06).
      Functional Independence Measure scores were not different between groups at any
      of the time periods (P>0.10). CONCLUSIONS: Data suggest that neuromuscular
      stimulation enhances the upper extremity motor recovery of acute stroke
      survivors. However, the sample size in this study was too small to detect any
      significant effect of neuromuscular stimulation on self-care function.

PMID- 9596246
TI  - Detecting psychiatric morbidity after stroke: comparison of the GHQ and the HAD
      Scale.
AB  - BACKGROUND AND PURPOSE: Mood disorders are common after stroke and may impede
      physical, functional, and cognitive recovery, making early identification and
      treatment of potential importance. We aimed to compare the accuracy of the
      General Health Questionnaire (GHQ-30) and the Hospital Anxiety and Depression
      (HAD) Scale in detecting psychiatric morbidity after stroke and to determine the
      most suitable cutoff points for different purposes. METHODS: One hundred five
      hospital-referred stroke patients completed both the GHQ-30 and HAD Scale 6
      months after onset before a blinded psychiatric assessment in which the Schedule
      for Affective Disorders and Schizophrenia with some supplementary questions was
      used to determine a DSM-IV (Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition) diagnosis. Measures were compared in terms of
      sensitivity, specificity, and receiver operating characteristic curves. RESULTS:
      No significant differences were found between the GHQ-30 and the HAD Scale in
      identifying those patients with any DSM-IV diagnosis (P=0.95), grouped depression
      (P=0.56), or anxiety (P=0.25) disorders. The previously recommended cutoff points
      for identifying "cases" for the GHQ (4/5) and for the HAD Scale (8/9 and 11/12)
      were found to be suboptimal in this population. CONCLUSIONS: The GHQ-30 and HAD
      scale exhibited similar levels of sensitivity and specificity. Data are
      presented, taking into account the "cost" of false-positives and negatives, to
      allow a choice of cutoff points suitable for differing situations.

PMID- 9596247
TI  - Assessment of clinical outcomes in acute stroke trials.
AB  - BACKGROUND AND PURPOSE: Adequate outcome assessment is crucial to randomized
      trials. We wished to assess the types of outcomes used in acute stroke trials and
      the appropriateness of these outcomes and their analyses. METHODS: Acute stroke
      trials from the Cochrane Stroke Group's database were included from 1955 to 1995
      if they were published in full text in English. For each trial we collected year
      of publication, number of patients randomized, blinding of outcome assessment,
      the specific outcome instruments used, the statistical methods used for analysis,
      and the significance of the results. The validity and reliability of each outcome
      measure were assessed by review of the literature. RESULTS: Our study included
      174 trials. Outcomes were assessed blindly in 69%. Death was recorded in only 76%
      of trials, impairment in 76%, disability in 42%, and handicap or quality of life
      in only 2%. Of the trials that measured impairment, 35% used a measure of
      established validity or reliability. For disability and handicap, the proportions
      with valid or reliable measures were 70% and 25%, respectively. Impairment and
      handicap measures were primarily analyzed as continuous variables, while
      disability was mainly analyzed as a dichotomous variable. Continuous data were
      usually analyzed with inappropriate parametric statistics. There was no
      relationship between the method of analysis, the type of outcome, and the
      statistical significance of results. CONCLUSIONS: Most acute stroke trials up to
      1995 have used clinical outcome measures that were inadequate in terms of their
      content, reliability, validity, blinded assessment, and statistical analysis.
      This has important implications for future stroke research.

PMID- 9596248
TI  - Circadian variation in the timing of stroke onset: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Acute myocardial infarction and sudden death display a
      circadian rhythm, with a higher risk between 6 AM and noon. Some reports suggest
      that stroke does not follow such a circadian variation and that hemorrhagic
      stroke occurs more often during the evening. METHODS: A meta-analysis of 31
      publications reporting the circadian timing of 11,816 strokes was performed,
      subdividing (when possible) by the type of stroke, according to the time of onset
      of symptoms. When precise timing was not given, strokes were distributed evenly
      (that is, biasing toward the null hypothesis of lack of circadian variation).
      RESULTS: All subtypes of strokes displayed a significant (P<0.001) circadian
      variation in time of onset, whether divided into 3-, 4-, or 6-hour time periods.
      There was a 49% increase (95% confidence interval, 44% to 55%) in stroke of all
      types between 6 AM and noon (compared with expectations if no circadian variation
      was present), which is a 79% (95% confidence interval, 72% to 87%) increase over
      the normalized risk of the other 18 hours of the day. There were 29% fewer
      strokes between midnight and 6 AM, a 35% decrease compared with the other 18
      hours of the day. All three subtypes of stroke had a significantly higher risk
      between 6 AM and noon (55% for 8250 ischemic strokes; 34% for 1801 hemorrhagic
      strokes, and 50% for 405 transient ischemic attacks). CONCLUSIONS: These data
      support the presence of a circadian pattern in the onset of stroke, with a
      significantly higher risk in the morning.

PMID- 9596249
TI  - Effects of acetazolamide on choroidal blood flow.
AB  - BACKGROUND AND PURPOSE: The acetazolamide provocation test is commonly used to
      study cerebrovascular vasomotor reactivity. On the basis of the effect of a
      carbonic anhydrase inhibitor in the central nervous system, we hypothesized that
      acetazolamide may also increase blood flow in the human choroid. METHODS: In a
      placebo-controlled, randomized, double-blind, three-way crossover design,
      acetazolamide (500 mg or 1000 mg i.v.) or placebo was administered to nine
      healthy subjects. The effect of acetazolamide was studied at 15-minute intervals
      for 90 minutes. Pulsatile choroidal blood flow was assessed with laser
      interferometric measurement of fundus pulsation. In addition, mean blood flow
      velocity and resistive index in the ophthalmic artery were measured with Doppler
      sonography. In a second study in six healthy subjects, we assessed the effect of
      acetazolamide (1000 mg i.v.) on intraocular pressure. RESULTS: Acetazolamide
      increased fundus pulsation amplitude in a dose-dependent manner (1000 mg: +33%;
      500 mg: +20%; P<0.001, ANOVA). The effect of acetazolamide on MFV (1000 mg: +18%;
      500 mg: +8%; P=0.003, ANOVA) and RI (1000 mg: -4%; 500 mg: -2%; P=0.006, ANOVA)
      was less pronounced but also significant. Acetazolamide did not induce any
      changes in systemic hemodynamic parameters but significantly decreased
      intraocular pressure (1000 mg: -37%; P<0.0001). CONCLUSIONS: The present data
      show for the first time that intravenously administered acetazolamide increases
      choroidal blood flow in humans. This phenomenon therefore indicates that the
      acetazolamide provocation test may qualify as a tool to investigate ocular
      vasomotor reactivity in a variety of ocular diseases. Moreover, the increase in
      choroidal blood flow after carbonic anhydrase inhibition can be expected to
      contribute to the therapeutic efficacy of carbonic anhydrase inhibitors in
      glaucoma.

PMID- 9596251
TI  - Apoptosis of motor neurons with induction of caspases in the spinal cord after
      ischemia.
AB  - BACKGROUND AND PURPOSE: Some neuronal subpopulations are especially vulnerable to
      ischemic injury. In the spinal cord, large motor neurons are vulnerable to
      ischemia and are selectively lost after transient ischemia. However, the
      mechanisms of the neuronal loss have been uncertain. We hypothesized that spinal
      motor neurons might be lost by apoptosis and investigated a possible mechanism of
      neuronal death by detection of double-strand breaks in genomic DNA and
      immunohistochemical analysis for caspases, ie, interleukin-1beta converting
      enzyme (ICE), Nedd-2, and CPP32. METHODS: We used a rabbit spinal cord ischemia
      model created with a balloon catheter. The spinal cord was removed at 8 hours, 1,
      2, or 7 days after 15 minutes of transient ischemia, and histological changes
      were studied with hematoxylin-eosin staining. To detect double-strand breaks in
      DNA, a staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      in situ nick end labeling (TUNEL) was performed. Furthermore, expression of ICE,
      Nedd-2, and CPP32 was investigated by Western blotting and immunohistochemical
      analysis. RESULTS: Motor neurons were selectively lost at 7 days after transient
      ischemia. TUNEL study demonstrated that no cells were positively labeled until 1
      day after ischemia, but nuclei of some motor neurons were positively labeled at 2
      days. Western blot analysis revealed no immunoreactivity for ICE and slight
      immunoreactivities for Nedd-2 and CPP32 in the sham-operated spinal cords.
      However, immunoreactivity became apparent at 8 hours after transient ischemia,
      decreased at 1 day, and returned to baseline level at 2 days. Immunohistochemical
      analysis demonstrated that motor neurons were responsible for induction of those
      caspases. CONCLUSIONS: Double-strand breaks in genomic DNA and induction of three
      caspases were demonstrated. These results indicate that motor neuron death in the
      spinal cord after transient ischemia is profoundly associated with activation of
      apoptotic processes.

PMID- 9596250
TI  - Dietary vitamin E levels affect outcome of permanent focal cerebral ischemia in
      rats.
AB  - BACKGROUND AND PURPOSE: A supraphysiological amount of vitamin E in the standard
      diet of laboratory animals may provide partial protection against cerebral
      ischemic damage in stroke models. The aim of the present study was to test the
      effect of dietary vitamin E on infarct volume in rats subjected to permanent
      focal cerebral ischemia. METHODS: Male Wistar rats were raised on a vitamin E
      deficient diet (n=10) or a control diet containing 62.7 mg vitamin E/kg (n=11)
      for 13 to 16 weeks, from the age of 3 weeks. The left middle cerebral artery
      (MCA) was permanently occluded by means of an intraluminal silicone-coated 3-0
      suture. Blood flow in the left MCA territory was measured before and after
      occlusion with laser Doppler flowmetry. The area of infarction was measured in
      hematoxylin-eosin-stained brain sections by means of an image analysis system.
      The investigator was not aware of the vitamin E status of the rats. RESULTS:
      Blood flow in the left MCA territory in the second half hour after occlusion was
      43+/-17% and 42+/-17% (mean+/-SD) of the baseline value in control and vitamin E
      deficient rats, respectively. The mean infarct volume, measured after 48 hours of
      survival, was 61+/-19 mm3 in control rats and 137+/-76 mm3 in vitamin E-deficient
      rats (P=0.037). CONCLUSIONS: After permanent focal cerebral ischemia, the infarct
      is larger in vitamin E-deficient rats than in rats raised on a diet with the
      usual, supraphysiological amount of vitamin E. This may have consequences for
      cerebral ischemia studies with experimental animals.

PMID- 9596252
TI  - Anticardiolipin antibody aggravates cerebral vasospasm after subarachnoid
      hemorrhage in rabbits.
AB  - BACKGROUND AND PURPOSE: We previously reported that patients with
      antiphospholipid antibodies (aPLs) frequently demonstrate cerebral infarction due
      to cerebral vasospasm after subarachnoid hemorrhage (SAH). To examine the
      participation of aPLs in the pathogenesis of vasospasm after SAH, we studied the
      relationships of aPLs and SAH in an animal model. METHODS: SAH was produced in 34
      rabbits that received two subarachnoid injections of autologous arterial blood.
      The animals were divided into four experimental groups: SAH was induced in group
      A (n=9), intracutaneous injection of cardiolipin (CL) was performed before the
      induction of SAH in group B (n=5), intravenous injection of CL was performed
      before SAH in group C (n=12), and cyclosporin A was infused intravenously after
      the intravenous injection of CL and induction of SAH in group D (n=8). Enzyme
      linked immunosorbent assay identifying the titer of IgG CL antibodies,
      neurological evaluation, cerebral angiography, and histological examination were
      performed in all four groups. RESULTS: A significant elevation of anti-CL
      antibodies, aggravation of neurological deficit, and reduction of caliber of the
      basilar artery were observed in rabbits that received the intravenous
      immunization of CL (group C). The administration of cyclosporin A reduced the
      titer of anti-CL antibody, aggravation of neurological deficit, constriction of
      basilar artery, and the incidence of cerebral infarction (group D). CONCLUSIONS:
      Anti-CL antibodies may therefore be involved in the deterioration of cerebral
      vasospasm after SAH.

PMID- 9596253
TI  - Matrix metalloproteinase expression increases after cerebral focal ischemia in
      rats: inhibition of matrix metalloproteinase-9 reduces infarct size.
AB  - BACKGROUND AND PURPOSE: Matrix metalloproteinases (MMPs) are a family of
      proteolytic enzymes that degrade the extracellular matrix and are implicated in
      numerous pathological conditions including atherosclerosis, inflammation, and
      tumor growth and metastasis. In the brain, the endothelial cell wall,
      strengthened by tight junctions, defines the blood-brain barrier (BBB). The
      extracellular matrix molecules constitute the basement membrane underlying the
      vasculature and play a critical role in maintaining the integrity of the BBB.
      After focal stroke, there is a breakdown of the BBB with an associated increase
      in vascular permeability, inflammatory cell influx, and neuronal cell death. The
      present study was designed to investigate the effects of MMP expression after
      stroke. METHODS: Focal stroke was produced by permanent middle cerebral artery
      occlusion (MCAO) in the rat, and MMP protein expression was measured by Western
      blot and zymogram analysis over a time course ranging from 6 hours to 30 days
      (n=32). Immunohistochemistry at 1 and 5 days (n=8 and 6, respectively) was also
      utilized to characterize the expression of several MMPs and related proteins
      after stroke, including their cellular source. To test the hypothesis that early
      increased MMP-9 expression is involved in ischemic brain injury, a neutralizing
      monoclonal antibody directed against MMP-9 was administered intravenously (n=7
      per group) 1 hour before MCAO, and infarct size was measured 24 hours later.
      RESULTS: MMP expression increased progressively over time after stroke. After 12
      hours, significant (P<0.05) MMP-9 activity was observed that reached maximum
      levels by 24 hours (P<0.001), then persisted for 5 days at this level and
      returned to basal (zero) levels by 15 days. On the basis of morphological
      criteria, MMP-9 appeared to stain with endothelial cells and neutrophils
      identified both within and at the periphery of the infarct within 24 hours of
      focal ischemia. After 5 days, MMP-9 appeared to stain with macrophages present
      within the infarcted brain. MMP-2 activity was significantly (P<0.001) increased
      by 24 hours and was maximum after 5 days following MCAO. MMP-2 appeared to stain
      with macrophages present within the infarcted region. Unlike MMP-9 and MMP-2,
      tissue inhibitor of metalloproteinase-1 was identified at comparable levels in
      both control and ischemic tissue after MCAO. MMP-1 and MMP-3 could not be
      detected in the brain after focal stroke. When an MMP-9-neutralizing monoclonal
      antibody was administered systemically, animals exhibited significantly reduced
      infarct size (ie, a 30% reduction compared with non-immune antibody controls;
      P<0.05). CONCLUSIONS: These results demonstrate that early increased MMP-9
      expression in endothelial cells and infiltrating neutrophils is a significant
      response to cerebral focal ischemia and that selective inhibition of MMP-9
      activity can significantly reduce brain injury after stroke.

PMID- 9596254
TI  - Effect of chronic nitric oxide deficiency on angiotensin II-induced hypertrophy
      of rat basilar artery.
AB  - BACKGROUND AND PURPOSE: Although in vitro studies suggest that nitric oxide has
      an inhibitory effect on cellular proliferation and migration, in vivo experiments
      failed to support this conclusion. The present study was designed to determine
      the effect of endogenous nitric oxide on angiotensin II-induced hypertrophy of
      small arteries in vivo. METHODS: Angiotensin II (200 ng/kg per minute), alone or
      in combination with N(omega)-nitro-L-arginine methyl ester (L-NAME) (60 mg/kg per
      day), was administered for 2 weeks in normotensive rats. Basilar arteries were
      harvested, and their geometry was determined in perfused and pressurized
      conditions. RESULTS: Angiotensin II increased media thickness, media-lumen ratio,
      and cross-sectional area of the arteries, confirming the presence of hypertrophic
      remodeling. The concomitant administration of L-NAME, an inhibitor of nitric
      oxide synthesis, prevented vascular hypertrophy. The remodeling of the basilar
      artery geometry in the combined treatment was of eutrophic nature, similar to
      that observed with the administration of L-NAME alone. CONCLUSIONS: Our results
      suggest that endogenous nitric oxide does not inhibit angiotensin II-induced
      vascular hypertrophy in vivo. Nitric oxide may even be a necessary factor for
      hypertrophy to develop.

PMID- 9596255
TI  - Core and penumbral nitric oxide synthase activity during cerebral ischemia and
      reperfusion.
AB  - BACKGROUND AND PURPOSE: The present studies examined the hypothesis that the
      distribution of cerebral injury after a focal ischemic insult is associated with
      the regional distribution of nitric oxide synthase (NOS) activity. METHODS: Based
      on previous studies that certain anatomically well-defined areas are prone to
      become either core or penumbra after middle cerebral artery occlusion (MCAO), we
      measured NOS activity in these areas from the right and left hemispheres in a
      spontaneously hypertensive rat filament model. Four groups were studied: (1)
      controls (immediate decapitation); (2) 1.5 hours of MCAO with no reperfusion
      (R0); (3) 1.5 hours of MCAO with 0.5 hour of reperfusion (R0.5); and (4) 1.5
      hours of MCAO with 24 hours of reperfusion (R24). Three groups of corresponding
      isoflurane sham controls were also included: 1.5 (S1.5) or 2 (S2.0) hours of
      anesthesia and 1.5 hours of anesthesia+24 hours of observation (S24). RESULTS:
      Control core NOS activity for combined right and left hemispheres was 129%
      greater than penumbral NOS activity (P<0.05). Combined core NOS activity was also
      greater (P<0.05) in the three sham groups: 208%, 122%, and 161%, respectively. In
      the three MCAO groups, ischemic and nonischemic core NOS remained higher than
      penumbral regions (P<0.05). However, NOS activity was lower in the ischemic than
      in the nonischemic core in all three groups: R0 (29% lower), R0.5 (48%), and R24
      (86%) (P<0.05). Addition of cofactors (10 micromol/L tetrahydrobiopterin, 3
      micromol/L flavin adenine dinucleotide, and 3 micromol/L flavin mononucleotide)
      increased NOS activity in all groups and lessened the decrease in ischemic core
      and penumbral NOS. CONCLUSIONS: Greater NOS activity in core regions could
      explain in part the increased vulnerability of that region to ischemia and could
      theoretically contribute to the progression of the infarct over time. The data
      also suggest that NOS activity during ischemia and reperfusion could be
      influenced by the availability of cofactors.

PMID- 9596256
TI  - Glutamate, glutamine, and GABA as substrates for the neuronal and glial
      compartments after focal cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: Even though the utilization of substrates alternative to
      glucose may play an important role in the survival of brain cells under ischemic
      conditions, evidence on changes in substrate selection by the adult brain in vivo
      during ischemic episodes remains very limited. This study investigates the
      utilization of glutamate, glutamine, and GABA as fuel by the neuronal and glial
      tricarboxylic acid cycles of both cerebral hemispheres after partially reversible
      focal cerebral ischemia (FCI). METHODS: Right hemisphere infarct was induced in
      adult Long-Evans rats by permanent occlusion of the right middle cerebral artery
      and transitory occlusion of both common carotid arteries. (1,2-13C2) acetate was
      infused for 60 minutes in the right carotid artery immediately after carotid
      recirculation had been re-established (1-hour group) or 23 hours later (24-hour
      group). Extracts from both cerebral hemispheres were prepared and analyzed
      separately by 13C nuclear magnetic resonance and computer-assisted metabolic
      modeling. RESULTS: FCI decreased the oxidative metabolism of glucose in the brain
      in a time-dependent manner. Reduced glucose oxidation was compensated for by
      increased oxidations of (13C) glutamate and (13C) GABA in the astrocytes of the
      ipsilateral hemispheres of both groups. Increased oxidative metabolism of (13C)
      glutamine in the neurons was favored by increased activity of the neuronal
      pyruvate recycling system in the 24-hour group. CONCLUSIONS: Data were obtained
      consistent with time-dependent changes in the utilization of glutamate and GABA
      or glutamine as metabolic substrates for the glial or neuronal compartments of
      rat brain after FCI.

PMID- 9596257
TI  - White matter changes in the gerbil brain under chronic cerebral hypoperfusion.
AB  - BACKGROUND AND PURPOSE: An animal model of chronic cerebral hypoperfusion was
      developed with coiled clips applied to both carotid arteries of adult Mongolian
      gerbils for between 1 week and 2 months. In the brain of this animal model,
      rarefaction of white matter with dilatation of the ventricles was frequently
      observed. To better understand the mechanism of white matter alteration under
      cerebral hypoperfusion, the chronological sequence of molecular changes in the
      cerebral white matter of the animal model was determined. METHODS: Specially
      designed coiled clips were placed around both carotid arteries of Mongolian
      gerbils to create stenosis without occlusion. Changes in levels of myelin basic
      protein (MBP) as a marker of myelin, neurofilament H (NFH) as a marker of axonal
      proteins, and glial fibrillary acidic protein (GFAP) in astroglia after 2 months
      of cerebral hypoperfusion were analyzed with Western blotting and enzyme-linked
      immunosorbent assay. RESULTS: Western blotting of the white matter after 2 months
      of hypoperfusion showed that the levels of MBP and NFH decreased, whereas that of
      GFAP increased. The time course of MBP and NFH changes determined with enzyme
      linked immunosorbent assay revealed that the change of MBP preceded that of NFH.
      CONCLUSIONS: In the present study it was shown that the damage to myelin precedes
      that to the axon in the white matter in a chronic cerebral hypoperfusion animal
      model, suggesting that the change in myelin is the primary pathological event in
      the cerebral white matter under chronic hypoperfusion. The present study may help
      in understanding the mechanisms of white matter pathology in leukoaraiosis.

PMID- 9596258
TI  - Cervical carotid artery vasospasms causing cerebral ischemia: detection by
      immediate vascular ultrasonographic investigation.
AB  - BACKGROUND: The etiology of cerebral ischemic accidents in young adults often
      remains unclarified. CASE DESCRIPTION: A 32-year-old woman presented after
      multiple episodes of left monocular visual impairment and right-sided focal
      signs. MRI revealed a low-flow infarction on the left; color-coded duplex
      sonography (CCDS), however, showed normal vascular findings. During the inpatient
      rehabilitation, a renewed visual impairment occurred; an immediate CCDS
      examination now demonstrated a filiform stenosis of the left internal carotid
      artery (ICA) 4 cm above the origin and indirect signs of a severe stenosis of the
      right ICA. Results of a follow-up examination 18 hours later were again normal.
      Six weeks later, on reoccurrence of visual impairment, a reversible stenosis of
      the left ICA was again demonstrated. A search for possible causes of vasospasm
      was unsuccessful. After treatment with calcium antagonists the patient was free
      of complaints (with the exception of 3 very short attacks of visual impairment)
      during the following 12 months. CONCLUSIONS: Cervical carotid artery vasospasms
      can apparently occur spontaneously without a mechanical trigger. Because their
      detection is difficult, vasospasms may go undetected.

PMID- 9596259
TI  - Lubeluzole treatment of acute ischemic stroke.

PMID- 9596260
TI  - Fou rire prodromique and ischemic stroke.

PMID- 9596261
TI  - Transcranial Doppler and stump pressure during carotid endarterectomy.

PMID- 9596262
TI  - Microembolic signals under increased ambient pressure.

PMID- 9596263
TI  - Contrast-enhanced transcranial color-coded real-time sonography: a reliable tool
      for the diagnosis of middle cerebral artery trunk occlusion in patients with
      insufficient temporal bone window.

PMID- 9596264
TI  - Prognostic factors in the pathological assessment of prostate cancer.

PMID- 9596265
TI  - The interrelationship between tubular and papillary sectors of tubulo-villous
      colorectal adenomas: comparative morphometric analysis and evaluation of cell
      proliferation.
AB  - In a series of 100 colorectal adenomas, 23 tubulo-villous adenomas were
      individualized through the identification of papillae as structures persisting
      for more than 100 microm in serial sections with a connective axis lined with
      epithelial cells. In these adenomas, the tubular and villous areas with the
      highest dysplasia were selected, and a morphometric analysis was undertaken to
      assess the Index of Structural Atypia, the Nucleo-Glandular Index, and the
      Nuclear Stratification Index. The AgNor count and the proliferating cell nuclear
      antigen (PCNA) Label Index (LI) also were performed. The overall mean of each of
      these indexes was significantly higher in the villous sector than in the tubular
      one (P < .001). In 16 cases, the semi-objective method of dysplasia gradation
      showed a superior degree in the papillary sector, whereas it showed an equal
      degree in the remaining seven lesions. The AgNOR count was significantly
      different in all cases, with higher values in villous sectors (P < .05). With the
      exception of one case, this was confirmed by the PCNA LI. The Stratification
      Index showed significantly different values in 20 cases, whereas the other
      morphometric indexes showed a less discriminatory result. Our findings
      objectively show that the degree of dysplasia in tubulo-villous adenomas should
      be analyzed in the villous sector. The existence of heterogeneous cellular
      populations has been confirmed both in the structural organization of cells and
      in some basic parameters such as the cell proliferation rate in colorectal
      adenomas. Our findings suggest that the occurrence of villous architectural
      growth is a secondary event in a tubular adenoma. Enhanced cellular proliferation
      of the villous area allows the progressive substitution of tubular structures.

PMID- 9596266
TI  - Chondromyxoid fibroma of bone: a clinicopathologic review of 278 cases.
AB  - In a study of the clinical, radiographic, and pathological features of
      chondromyxoid fibroma, the tumor was slightly more common in men, usually in the
      second decade of life. Almost half of the tumors involved the long bones,
      although the ilium and the small bones were also common sites. Roentgenograms
      showed a sharply marginated, lobulated, lucent defect in the metaphysis. The
      tumor involved the medullary bone in an eccentric fashion, and the cortex was
      thinned and expanded. Periosteal reaction and soft tissue extension were
      uncommon. Mineralization was identified in 13% of the lesions. Histologically,
      the tumors were almost always arranged in lobules, which were prominent
      (macrolobular) or somewhat indistinct (microlobular). The tumor cells were
      spindle-shaped or stellate and arranged in a myxoid matrix. Calcification was
      seen in more than one third of the cases but was rarely prominent. Hyaline
      cartilage and chondroblastoma-like areas were not uncommon. Approximately 18% of
      tumors showed bizarre nuclei. Permeation of bony trabeculae was uncommon.
      Treatment was conservative surgical removal; approximately one fourth of the
      patients had recurrence.

PMID- 9596267
TI  - Defective basement membrane in laryngeal carcinomas with heterogeneous loss of
      distinct components.
AB  - In this study, we evaluated immunohistochemically the composition of the tumor
      associated epithelial basement membrane (BM) in a series of 66 laryngeal squamous
      cell carcinomas (SCC) and compared these results with those from 10 cases with
      laryngeal dysplasia and five cases with normal mucosa (controls). The major BM
      components collagen IV and VII, laminin-1, perlecan (heparan sulfate
      proteoglycan), and fibronectin were evaluated. The extent of the retained BM
      material was quantified by semiautomated morphometry. A subsequent statistical
      analysis correlated the immunohistochemical findings with the histopathologically
      evaluated degree of tumor cell differentiation. In our series, we observed a
      distinct correlation between the degree of tumor cell differentiation and the
      amount of retained BM material. The loss of BM affected the various components
      differently, with a more extensive loss of collagen VII even in highly
      differentiated tumors and a progressive loss of collagen IV immunostaining with
      decreasing tumor cell differentiation. With respect to the other BM components, a
      stepwise loss of BM material also was seen with decreasing degree of the tumor
      cell differentiation. This loss, however was not at a statistically significant
      level, so these parameters did not show further statistically relevant data. In
      dysplastic lesions (regardless of the degree of dysplasia), focal BM disruptions
      were seen that affected the various BM components to a very similar extent. Our
      observations provide evidence that laryngeal carcinomas show a progressive loss
      of BM material along with decreasing tumor cell differentiation. This loss of BM,
      however, affects the various BM components differently. This indicates a
      dysregulation of the BM, either induced by uncoordinated neosynthesis or
      selectively enhanced degradation by proteases or both. Finally, the BM analysis
      may provide information on the biological course of the tumors. The loss of
      collagen VII may serve as a marker for "early" invasive tumor growth, whereas the
      amount of collagen IV provides significant information on the loss of tumor cell
      differentiation.

PMID- 9596268
TI  - Prognostic significance of p53, bcl-2, vimentin, and S100 protein-positive
      Langerhans cells in endometrial carcinoma.
AB  - Immunohistochemical expression of p53, Bc12, vimentin, and S100 protein-positive
      Langerhans cell was evaluated in 50 endometrial carcinomas (6 stage I, 14 stage
      II, 20 stage III, and 10 stage IV), in an attempt to use these markers as
      predictors of survival. Monoclonal antibodies to p53, Bcl-2, vimentin, and S100
      proteins were applied to paraffin-embedded sections of endometrial
      adenocarcinoma, using the avidin-biotin peroxidase complex technique (ABC). All
      20 patients with stage I and II carcinomas were alive with a mean follow-up of 3
      years. Of 30 patients with stage III and IV carcinomas, 13 died of tumor (3-year
      survival, 57%; SE, 10%), eight were alive with tumor, and nine were alive with no
      evidence of tumor (mean follow-up, 46 months). Strong p53 positivity was present
      in 11 carcinomas (22%), including nine high-stage and two low-stage tumors. Bcl-2
      positivity was identified in 33 tumors (66%). These tumors were mostly low stage;
      however, no correlation was found between Bcl-2 expression and prognosis.
      Vimentin positivity (P < .001), and tumor infiltration by a large number of S100
      protein-positive Langerhans cells (P < .05) were associated with low-stage
      tumors. Vimentin was expressed in 23 carcinomas, including 70% of low-stage
      tumors and 20% of high-stage tumors. Most high-grade carcinomas were Langerhans
      cell depleted; most low-grade carcinomas showed >50 S100 protein-positive
      Langerhans cells/10 high-power fields. Our results indicate that Langerhans cell
      infiltration and vimentin positivity of tumor cells are favorable prognostic
      factors in endometrial carcinomas.

PMID- 9596269
TI  - Amyloid myopathy: clinicopathologic study of 16 cases.
AB  - Amyloid deposition in skeletal muscle is a well-recognized but rare occurrence.
      Sixteen such cases seen in a 17-year period (1979 to 1996) out of a total of
      3,937 muscle biopsy specimens (0.004%) form this study group. Either Congo red or
      sulfated alcian blue stains were routinely performed in each biopsy to screen for
      amyloid. Patients in this study (eight men, eight women) ranged in age from 42 to
      90 years (mean, 61 years) at initial presentation. The most common symptoms at
      presentation included weakness/fatigue (n = 10), autonomic symptoms (n = 8), and
      weight loss/decreased appetite (n = 7). Five patients had a concomitant
      malignancy (myeloma, n = 3; malignant carcinoid tumor, n = 1; melanoma, n = 1).
      Two patients had known hereditary forms of amyloidosis. Five patients had amyloid
      diagnosed on another organ biopsy (excluding peripheral nerve). Histologically,
      amyloid was deposited in the interstitium or perivascular region in 14 muscles
      and endomysial region in seven muscles. All cases were confirmed with Congo red
      staining (apple green birefringence) or by electron microscopic identification of
      fibrillary amyloid material. Scattered angular atrophic esterase-positive muscle
      myofibers indicative of acute denervation atrophy were seen in 14 muscles. Eight
      muscles showed small group atrophy, and seven showed myofiber type grouping.
      Scattered regenerating muscle fibers were seen in nine cases, degenerating
      myofibers in six, and foci of chronic endomysial and perivascular inflammation in
      two. Four muscles showed type II muscle fiber atrophy. A concomitant sural nerve
      biopsy specimen was evaluated in seven patients; all seven contained amyloid,
      confirmed either by Congo red staining or electron microscopic examination. In
      two nerves, there was a mild loss of myelinated axons; four had a moderate loss,
      and one, severe loss. Six of seven nerves showed predominantly axonopathic
      changes. In conclusion, (1) the prevalence rate of amyloid myopathy in muscle
      biopsy specimens was low (in this series, 0.004%); (2) only a minority of
      patients had multiple myeloma, and most presented with muscle weakness/fatigue or
      autonomic symptoms; (3) most of the muscles showed neurogenic features
      histologically; (4) all concomitant sural nerve biopsy specimens contained
      amyloid, and most showed a predominance of axonopathic changes.

PMID- 9596270
TI  - Aberrant crypt foci in human colons: distribution and histomorphologic
      characteristics.
AB  - Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic, and in
      some cases, neoplastic lesions in human colons. These microscopic lesions,
      identified on methylene blue-stained mucosa with a low-power-magnification
      microscope, are thought to be closely related to the earliest steps in multistage
      colonic tumorigenesis. We investigated the distribution pattern and
      histomorphological features of ACF in 74 patients with sporadic colorectal
      cancer. The distribution pattern shows a slightly higher prevalence with older
      age. The prevalence of the ACF in sigmoid colon was significantly higher in
      patients with colorectal cancer as compared with patients with benign colonic
      diseases. Also, significantly more ACF were detected in distal parts of the large
      bowel (descending, sigmoid colon, and rectum) than in proximal parts. Of 42
      microdissected lesions, 12 were dysplastic and 30 were hyperplastic foci. The
      average size of dysplastic lesions was significantly larger than hyperplastic
      foci. More apoptotic bodies were found in dysplastic lesions. These lesions also
      showed an upward expansion of proliferative compartment and higher proliferation
      indices expressed as proliferating cell nuclear antigen-labeling index. Lymphoid
      follicles were frequently observed in the base of both hyperplastic and
      dysplastic foci (40% and 66.6%, respectively). The coincidence of lymphoid
      follicles was 2.5 to 8 times higher than expected. These features may be related
      to further progression of selected ACF during colorectal tumorigenesis.

PMID- 9596271
TI  - Different patterns of DNA copy number changes in gastrointestinal stromal tumors,
      leiomyomas, and schwannomas.
AB  - It is not uniformly agreed whether gastrointestinal stromal tumors (GISTs) are
      phenotypical variants of leiomyomas (cellular leiomyomas) or whether they
      represent a separate, genotypically definable entity. In an attempt to solve this
      question, we examined immunohistochemically defined leiomyomas from the esophagus
      and uterus, gastric schwannomas, and benign gastrointestinal stromal tumors
      (GIST) by comparative genomic hybridization (CGH). All 14 leiomyomas (nine
      esophageal, five uterine) were actin- and desmin-positive but negative for CD34
      and S100-protein. Changes in DNA copy numbers were seen only in three esophageal
      leiomyomas. Gains were observed in chromosomes 3, 4, 5, 8, and 17, whereas losses
      were seen in 16p. All schwannomas were positive for S100-protein and negative for
      actin, desmin, and CD34. In schwannomas, the only change by CGH was a gain in 11q
      in one case. The benign GISTs, all from the stomach, were positive for CD34 but
      negative for desmin and S100-protein; two cases were positive for actin. The CGH
      findings in the GISTs differed markedly from those in leiomyomas and schwannomas.
      Ten of the 13 cases (77%) showed DNA copy number losses in 14q, and additional or
      other losses were found in eight cases, most often in chromosome 22 (seven
      cases), 15 (three cases), and 1p (two cases). Furthermore, two of the GISTs
      showed gains in 5q. These results indicate that phenotypically undifferentiated
      GISTs are also genetically different from leiomyomas and schwannomas and support
      their classification apart from leiomyomas.

PMID- 9596272
TI  - DNA index shift with disease progression in colorectal adenocarcinoma: a
      morphological and flow cytometric study.
AB  - DNA index (DI) values seen in 86 sporadic colorectal adenocarcinomas were related
      to clinical, morphological, and disease progression features. DI, whose overall
      distribution was bimodal with peaks in the diploid and from hypotriploid to
      tetraploid ranges, was related to pathological lymph node staging (pN), staging,
      lymphoid reaction, and tubular configuration. With increasing severity in
      pathological features, an irregular shift in DI class prevalence was seen, with
      no steady increase from diploidy to higher degrees of aneuploidy. All UICC stage
      I tumors (13% of total) were aneuploid, 50% being hypertriploid; diploidy (35%)
      and hypertriploidy (22%) prevailed in stage II carcinomas (41% of total),
      diploidy (35%) and hypotriploidy (30%) in stage III (30% of total), and triploidy
      (33%) in stage IV (15% of total). Amongst features related to stage (lymphoid
      reaction, depth of neoplastic embolization, grading, tubular configuration, and
      polymorphism), few were associated with DI, and none influenced DI shift and
      class prevalence through the stages. The biological capabilities of colorectal
      adenocarcinoma in relation to stage are expressed by certain aneuploid DI classes
      (hypertriploidy: absence of extracolonic spread; hypotriploidy: lymph node
      metastases; triploidy: distant metastases). Diploidy is unrelated to criteria
      defining stage above I and predicts 50% of cases with development of metachronous
      metastases. Irregular DI class shift through the stages may be attributable to
      different pathways of cancerogenesis and disease progression in diploid versus
      aneuploid carcinomas. Alternatively, assuming that the diploid fraction in
      aneuploid tumors contains neoplastic cells, pure diploid carcinomas represent the
      selection of a vital clone that may give rise to a further mixed population whose
      aneuploid DI is different and best fitted to express the biological capabilities
      of that given stage.

PMID- 9596273
TI  - Tracing the origin of adenocarcinomas with unknown primary using
      immunohistochemistry: differential diagnosis between colonic and ovarian
      carcinomas as primary sites.
AB  - To discriminate adenocarcinoma metastases originating from either colon or ovary,
      a panel of immunohistochemical markers was evaluated. For this purpose, paraffin
      sections from 157 primary and metastatic colonic and ovarian carcinomas were
      immunostained. These cases were divided into a learning group of 46 colonic and
      54 ovarian carcinomas and a test group of 29 colonic and 28 ovarian carcinomas,
      including all metastatic tumors, among which were five with unknown primary site
      at the time of testing. The sections were immunostained with antibodies against
      carcinoembryonic antigen (CEA), cytokeratin 7 (CK7), cytokeratin 20 (CK20),
      CA125, vimentin, and CA19.9. Staining results were expressed as the product of
      staining intensity and percentage of positive tumor cells. Stepwise discriminant
      analysis was applied on the learning set to obtain a classification function for
      both tumors. The validity of the classification function was evaluated using the
      test set. There was considerable overlap in immunostaining for both tumor types,
      but colonic carcinomas were typically positive for CEA and CK20 and negative for
      CK7 and CA125. Ovarian carcinomas were typically positive for CK7 and CA125 and
      negative for CEA and CK20. In discriminant analysis, the best combination of
      markers appeared to be CK7 and CEA. Only one sample of the test group (2%) was
      misclassified. Taking learning and test groups together, 136 of the 157 samples
      (87%) were correctly classified with high posterior probability (PP > .8).
      However, from the 28 mucinous ovarian carcinomas, only 19 (68%) could correctly
      be classified with high PP. When excluding the nonmucinous ovarian carcinomas
      from the analysis, overall 87 of 103 (84.5%) of the samples were correctly
      classified (PP > .8) with a combination of CEA, CK7, and also vimentin. From the
      28 mucinous ovarian carcinomas, only two (7%) were misclassified, and four could
      not be classified with sufficient certainty. In neither analysis did CK20, CA125,
      or CA19.9 emerge as discriminatory parameters. Based on the same data, an
      intuitive flow chart was constructed with which 129 of 157 cases could be
      classified (only one falsely) without further statistical analysis. The five
      metastases with an at first unknown primary could, according to the follow-up,
      all be classified correctly with high PP. Most ovarian carcinomas, including the
      mucinous ones, can be discriminated with high probability from colonic carcinomas
      using a panel of three antibodies directed against CEA, cytokeratin 7, and
      vimentin.

PMID- 9596274
TI  - Paraffin section detection of the c-kit gene product (CD117) in human tissues:
      value in the diagnosis of mast cell disorders.
AB  - The c-kit gene product (CD117) is known to be expressed by a variety of normal
      human tissue cell types, including breast epithelium, germ cells, melanocytes,
      immature myeloid cells, and mast cells. To further characterize the expression of
      this antigen, 117 normal human tissues and 576 human tumors were studied by
      paraffin section immunohistochemistry. Varying degrees of CD117 expression were
      identified in various normal cells and in 53% of all tumors studied. In most
      cases (42% of total), CD117 expression was weak. Expression was most common in
      mast cell disease (100%), testicular germ cell tumors (100%), endometrial
      carcinomas (100%), papillary and follicular thyroid carcinomas (100%), small cell
      carcinomas (91%), malignant melanomas (90%), and ovarian epithelial carcinomas
      (87%). Strong immunoreactivity was only identified in cases of mast cell disease
      (11 of 11 cases), serous ovarian carcinoma (3 of 16), malignant melanoma (2 of
      40), small cell lung carcinoma (one of seven), and adenoid cystic carcinoma (one
      of one). Although the pattern of reactivity was primarily cytoplasmic, a membrane
      staining pattern was seen in a subset of cases, and strong membrane staining was
      identified in normal mast cells and all cases of mast cell disease. The lack of
      tumor specificity of weak expression of this antigen limits its diagnostic
      utility in most cases. However, the strong membrane reactivity for CD117
      identified in mast cells may be useful in the diagnosis of mast cell disorders.

PMID- 9596275
TI  - Prevalence of the partial molar phenotype in triploidy of maternal and paternal
      origin.
AB  - Triploid partial moles are at risk for trophoblastic neoplasia, yet the
      prevalence, parent of origin, and evolution of the partial molar phenotype
      amongst all triploids remains controversial. We determined parental origin by
      polymerase chain reaction (PCR) analysis, stage of development by gross and
      histological criteria, and partial molar status according to strict diagnostic
      criteria for all triploids identified amongst 1,054 consecutively karyotyped
      spontaneous abortions. Triploidy was detected in 64 of 832 successfully
      karyotyped specimens. Complete data were collected in 59 cases. Diandric origin
      was found in 39 specimens, and 20 of these fulfilled all four criteria for
      partial mole (trophoblast hyperplasia, dimorphic population of large and small
      villi, villous hydrops greater than 0.5 mm, and irregular villous contour). We
      separated the 19 diandric triploids not fulfilling all criteria for partial mole
      into four groups: specimens of early developmental stage, which we believed
      represented developing ("early") partial moles (n = 3), cases of late
      developmental stage, which we believed represented involuting ("ancient") partial
      moles (n = 4), cases showing some but not all criteria for partial mole (n = 7),
      and specimens with few if any criteria suggestive of partial mole (n = 5). In
      triploids of digynic origin (n = 20), developmental stage was significantly
      lower, fetal tissue was more frequently identified, and all specimens showed well
      preserved fetal red blood cells. Digynic triploids occasionally showed irregular
      contour, dimorphic villi, and a mild form of trophoblast hyperplasia but never
      showed hydropic degeneration and were never suspicious for partial mole.

PMID- 9596276
TI  - Diffuse lymphoplasmacytic acalculous cholecystitis: a distinctive form of chronic
      cholecystitis associated with primary sclerosing cholangitis.
AB  - Inflammation of the gallbladder is known to occur in patients with primary
      sclerosing cholangitis (PSC). However, the histological features of this form of
      cholecystitis have not been adequately defined. The aim of this study was to
      compare the inflammatory lesions of PSC-associated cholecystitis with those
      present in other cholecystopathies. The cases consisted of 11 gallbladders from
      patients with PSC who underwent liver transplantation. As controls, gallbladders
      from liver transplant patients with primary biliary cirrhosis (n = 4) and other
      chronic nonbiliary hepatopathies (n = 8), and 13 cholecystectomies from patients
      with chronic cholecystitis with (n = 10) and without (n = 3) lithiasis, were
      studied. The following histological features were tabulated on coded slides:
      presence, depth of involvement, and distribution of the inflammatory infiltrate,
      predominant cell type, presence of lymphoid aggregates, epithelial damage,
      metaplastic changes (pyloric or intestinal), fibrosis, smooth muscle hypertrophy,
      and presence of Rokitansky-Aschoff sinuses. At variance with the wide range of
      histological abnormalities present in other forms of chronic cholecystitis, most
      PSC-related cholecystitis showed a diffuse infiltrate (6 of 11) rich in plasma
      cells (6 of 11) predominantly confined to the lamina propria (9 of 11). The
      combination of these three features was present exclusively in PSC (5 of 11 PSC
      cholecystitis compared with 0 of 25 controls; P = .001). In conclusion, this
      study suggests that a characteristic form of cholecystitis may develop in
      patients with PSC.

PMID- 9596277
TI  - Utilization of molecular genetics in the differentiation between adrenal cortical
      adenomas and carcinomas.
AB  - Distinction between benign adrenal cortical proliferative lesions and adrenal
      cortical carcinoma has been approached by a combination of histological,
      immunohistochemical, and macroscopical parameters. Modern imaging studies allow
      detection of small adrenal cortical lesions that may be incorrectly diagnosed.
      Differentiation between benign and malignant tumors of the adrenal cortex was
      attempted by microdissection of nine cases of adrenal cortical hyperplasia, 10
      cortical adenomas, and 18 adrenal cortical carcinomas with subsequent polymerase
      chain reaction (PCR) amplification for loss of heterozygosity (LOH) of five
      microsatellites of putative tumor suppressor gene loci: p53 gene (17p), the
      neuroblastoma candidate gene (1p), the p16 gene (9p), the von Hippel Lindau gene
      (3p), and the retinoblastoma gene (13q). None of the hyperplastic lesions or
      cortical adenomas showed LOH of any of the gene markers used. Conversely, genetic
      changes were observed in 61% (11 of 18) of the cases of carcinoma. Forty-four
      percent of the lesions showed LOH for p53 (7 of 16). LOH of 1p, 3p, and 9p were
      seen in 22%, 22%, and 26%, respectively. LOH of the retinoblastoma gene was seen
      in 80% or four of five of the informative cases studied. We conclude that LOH
      studies may be used to distinguish malignant from nonmalignant adrenal cortical
      proliferations. Relative infrequency of LOH in 3p may furthermore help to
      differentiate adrenal lesions from clear cell carcinomas of the kidney.

PMID- 9596279
TI  - Alterations in colonic mucosal vessels in patients with cirrhosis and
      noncirrhotic portal hypertension.
AB  - Changes in intestinal mucosal microvasculature as a cause of lower
      gastrointestinal hemorrhage in patients with portal hypertension have been well
      documented clinically, but the analogous histomorphological changes have not been
      well characterized. The goal of this study was to evaluate qualitative and
      quantitative changes in colonic mucosal vessels in patients with cirrhosis or
      clinically evident portal hypertension and to correlate these changes with
      endoscopic and clinical findings. Colon biopsy or resection specimen slides from
      46 patients with biopsy-proven cirrhosis (44 patients) or noncirrhotic portal
      hypertension (two patients) were reviewed. Immunoperoxidase stain for CD34
      antigen was used to facilitate visualization of mucosal vessels, and vessel
      diameter was measured with a micrometer. Patients with inflammatory bowel disease
      were excluded. Twenty-four normal colon biopsy specimens served as controls.
      Mucosal vessels were divided into superficial, intermediate, and deep layers. As
      a group, the cirrhotic patients had a significantly higher mean diameter of
      vessels in all three layers. Qualitatively, increased numbers of small vessels
      and prominent branching were noted, especially in the superficial and
      intermediate layers. Tortuous, thick-walled vessels, suggesting arterialization
      of venules, were present in some cases. Eleven patients had endoscopic findings
      suggestive of vascular abnormalities, including erythematous mucosal patches, red
      macules, and telangiectasias. Eighteen had esophageal varices, and five had
      portal gastropathy. Nineteen patients had gastrointestinal (GI) bleeding,
      localized to the lower GI tract in 11. These qualitative and quantitative
      findings suggest that colonic mucosal vascular lesions are common in portal
      hypertension and may represent a potential source of clinically significant lower
      GI hemorrhage in these patients.

PMID- 9596278
TI  - Prognostic markers in pheochromocytoma.
AB  - Clinical and histopathological features do not reliably distinguish between
      benign and malignant pheochromocytomas. Additional markers that might be useful
      prognostic indicators in the pathological assessment of these tumors are sought.
      Immunohistochemical expression of MIB-1, Bcl-2, cathepsin B, cathepsin D, basic
      fibroblast growth factor (bFGF), c-met, and type IV collagenase were studied on
      formalin-fixed tissue from 33 nonconsecutive cases of pheochromocytoma, selected
      on the basis of reliable long-term follow-up, to determine associations with
      malignancy. The study group included 33 patients, 19 men and 14 women, with a
      mean age of 45 years, including five cases of neurofibromatosis (NF), three
      familial, and one MEN IIb. Mean follow-up was 63.2 months. Ten patients were
      determined to have malignant pheochromocytomas by the presence of metastatic
      disease. Features found to be associated with malignancy included MIB-1 labeling
      index (5% vs 1%) (P = .0009), male gender (90% vs 43%) (P = .008), extra-adrenal
      location (40% vs 9%) (P = .03), tumor weight (481 g vs 124 g) (P = .05), and
      young age (38 years vs 49 years) (P = .05). None of the five cases with NF were
      malignant (P = .04). S-100 positivity showed a significant (P = .02) but
      nonlinear association with benign tumors. Absent S-100 correlated with greater
      tumor weight. Malignancy was not associated with right versus left side or
      bilaterality, although bilateral tumors were smaller. C-met, bFGF, cathepsin B,
      cathepsin D, and collagenase were strongly expressed in most tumors and were not
      predictive of outcome, nor was bcl-2, which was variably expressed. Using
      multiple logistic regression with malignancy as the dependent variable, MIB-1
      continued to show a significant association with malignancy (P = .005)
      independent of any association with sex, age, or extra-adrenal location. Using a
      cutoff value of MIB-1 labeling of greater than 3% yielded a specificity of 100%
      and a sensitivity of 50% in predicting malignancy.

PMID- 9596280
TI  - Expression of the RNA component of telomerase in Wilms tumor and nephrogenic rest
      recapitulates renal embryogenesis.
AB  - Telomerase is a ribonucleoprotein enzyme associated with cellular immortality and
      has been detected in the vast majority of adult tumors. Wilms tumor is a
      histologically diverse embryonal malignancy of childhood, and the histological
      features of Wilms tumor and its precursor lesion, the nephrogenic rest,
      recapitulate the components of normal renal embryogenesis. Both the epithelial
      and the stromal components of Wilms tumor arise by differentiation of primitive
      mesodermal blastema. We compared expression of the RNA component of human
      telomerase (hTR) in normal developing kidneys, Wilms tumors, and nephrogenic
      rests and correlated expression of hTR with cell proliferation. Using a
      radioactive in situ hybridization method, we examined archival material from 17
      Wilms tumors (including nine with nephrogenic rests), four therapeutically
      aborted embryos (37 to 56 days), three fetuses on whom autopsies had been
      performed, and one neonate for expression of hTR. Proliferative index was
      measured by immunohistochemical staining for MIB1. In the embryonic kidney, Wilms
      tumors, and nephrogenic rests, the patterns of hTR expression were similar:
      expression was usually maximal within the immature epithelial elements followed
      by the poorly differentiated blastema, but was weak or absent in the immature
      stroma. Mature tubules, glomeruli, and stroma were negative for hTR expression,
      as were differentiated heterologous elements present in post-therapy Wilms
      tumors. There was only a partial relationship between proliferative index and hTR
      expression. In the embryonic kidney, Wilms tumors, and nephrogenic rests,
      blastema had the highest proliferative index, whereas the indices were
      significantly lower in the immature epithelium and stroma. The proliferative
      index in mature and heterologous elements was low or zero. Thus, the pattern of
      hTR expression in Wilms tumor and its precursor lesion recapitulates
      embryogenesis precisely and may represent that aspect of the persistent fetal
      phenotype which predisposes to the development of malignancy.

PMID- 9596281
TI  - Prostatic adenocarcinoma with glomeruloid features.
AB  - A wide variety of architectural patterns of adenocarcinoma may be seen in the
      prostate. We have recently encountered a hitherto-undescribed pattern of growth
      characterized by intraluminal ball-like clusters of cancer cells reminiscent of
      renal glomeruli, which we refer to as prostatic adenocarcinoma with glomeruloid
      features. To define the architectural features, frequency, and distribution of
      prostatic adenocarcinoma with glomeruloid features, we reviewed 202 totally
      embedded radical prostatectomy specimens obtained between October 1992 and April
      1994 from the files of the Mayo Clinic. This series was supplemented by 100
      consecutive needle biopsies with prostatic cancer from January to February 1996.
      Prostatic adenocarcinoma with glomeruloid features was characterized by round to
      oval epithelial tufts growing within malignant acini, often supported by a
      fibrovascular core. The epithelial cells were sometimes arranged in semicircular
      concentric rows separated by clefted spaces. In the radical prostatectomy
      specimens, nine cases (4.5%) had glomeruloid features. The glomeruloid pattern
      constituted 5% to 20% of each cancer (mean, 8.33%) and was usually located at the
      apex or in the peripheral zone of the prostate. Seven cases were associated with
      a high Gleason score (7 or 8), one with a score of 6, and one with a score of 5.
      All cases were associated with high-grade prostatic intraepithelial neoplasia and
      extensive perineural invasion. Pathological stages included T2c (three cases),
      T3b (four cases), and T3c (two cases); one of the T3b cases had lymph node
      metastases (N1). Three (3%) of 100 consecutive routine needle biopsy specimens
      with cancer showed glomeruloid features, and this pattern constituted 5% to 10%
      of each cancer (mean, 6.7%). The Gleason score was 6 for two cases and 8 for one
      case. Two cases were associated with high-grade prostatic intraepithelial
      neoplasia, and one case had perineural invasion. Glomeruloid features were not
      observed in any benign or premalignant lesions, including hyperplasia and
      intraepithelial neoplasia. Glomeruloid structures in the prostate represent an
      uncommon but distinctive pattern of growth that is specific for malignancy.
      Glomeruloid features may be a useful diagnostic clue for malignancy, particularly
      in some challenging needle biopsy specimens. This pattern of growth is usually
      seen in high-grade adenocarcinoma, often with extraprostatic extension. Further
      investigations are required to determine its independent predictive value and
      correlation with stage and Gleason score.

PMID- 9596282
TI  - Radiofrequency ablation for sleep-disordered breathing.

PMID- 9596283
TI  - A scandalous incompetence...continued.

PMID- 9596284
TI  - Serum concentrations of the antimycobacterial drugs.

PMID- 9596285
TI  - Prescription of macrolides in community-acquired pneumonia: science or art?

PMID- 9596286
TI  - New macrolides or new quinolones as monotherapy for patients with community
      acquired pneumonia: our cup runneth over?

PMID- 9596287
TI  - Cystic fibrosis: when to consider lung transplantation?

PMID- 9596288
TI  - Urban air pollution: why is it a health problem?

PMID- 9596289
TI  - Radiofrequency volumetric tissue reduction of the palate in subjects with sleep
      disordered breathing.
AB  - STUDY OBJECTIVES: To evaluate pain, swallowing, speech, edematous response,
      tissue shrinkage, sleep, snoring, and safety (energy limits and adverse effects)
      following radiofrequency (RF) treatment to the palate in 22 subjects with sleep
      disordered breathing. DESIGN: This investigation is a prospective nonrandomized
      study. Polysomnography, radiographic imaging, and infrared thermography, along
      with questionnaires and visual analog scales, were used to evaluate the effects
      of RF treatment to the palate. SETTING: Treatments were delivered on an
      outpatient basis at Stanford University Medical Center. PATIENTS: Twenty-two
      healthy patients (18 men), with a mean age of 45.3+/-9.1 years, were enrolled.
      All were snorers seeking treatment and met predetermined criteria: a respiratory
      disturbance index < or = 15, oxygen saturation > or = 85%, and a complaint of
      daytime sleepiness. INTERVENTION: RF was delivered to the submucosa of the palate
      with a custom-fabricated electrode for a mean duration of 141+/-30 s with a mean
      of 3.6+/-1.2 treatments per patient. Reduction of their snoring scores determined
      the end point of the study. RESULTS: Neither speech nor swallowing was adversely
      affected. Pain was of short duration (0 to 48 h) and was controlled with
      acetaminophen. There were no infections. Although there was documented edema at
      24 to 48 h, there were no clinical airway compromises. Polysomnographic data
      showed improvement in esophageal pressure measurements of the mean nadir and the
      95th percentile nadir (p=0.031, p=0.001) respectively, as well as the mean sleep
      efficiency index (p=0.002). Radiographic imaging showed a mean shrinkage of 5.5+/
      3.7 mm (p< or =0.0001). Subjective snoring scores fell by a mean of 77% (8.3+/
      1.8 to 1.9+/-1.7, p=0.0001) accompanied by improved mean Epworth sleepiness
      scores (8.5+/-4.4 to 5.2+/-3.3, p=0.0001). CONCLUSION: The results of this
      investigation allowed the formulation of safety parameters for RF in this defined
      population with mild sleep-disordered breathing. There was a documented tissue
      reduction and improvement in symptoms in all subjects. However, given the small
      sample size and short-term follow-up, these results should be confirmed by
      further investigation.

PMID- 9596290
TI  - Underreading of the tuberculin skin test reaction.
AB  - STUDY OBJECTIVE: The tuberculin skin test is the best diagnostic method to detect
      tuberculous infection. How accurate is interpretation of the test? DESIGN:
      Observational study. SETTING: Both general hospital and university hospital.
      PARTICIPANTS: One hundred seven health-care professionals, including 52
      practicing pediatricians, 33 pediatric house officers, 10 pediatric academicians,
      11 registered nurses, and 1 pediatric nurse practitioner. STUDY: A tuberculin
      skin test (Mantoux) was applied to the arm of a known tuberculin converter. As
      participants entered/left the room, they were guided to the tuberculin converter.
      At no time did a participant observe readings other than his/her own. RESULTS:
      Mantoux tuberculin reaction measuring 15 mm induration was read individually by a
      group of 52 practicing pediatricians, 33 pediatric house officers, 10 pediatric
      academicians, 11 registered nurses, and one pediatric nurse practitioner. The
      median induration recorded by this group of 107 health-care professionals was 10
      mm, and 17 (33%) practicing pediatricians read the reaction as <10 mm induration.
      Using the > or = 15-mm induration indicator to identify a positive reaction, 93%
      of those in the study (99/107 participants) would have identified our known
      converter as tuberculin negative. CONCLUSION: This study confirms a general
      inaccuracy in interpretation of the tuberculin skin test reaction. It raises two
      questions. (1) Is there a general tendency toward underreading? (2) Does this
      general tendency to underread tuberculin skin test reactions raise some question
      as to the American Academy of Pediatrics, American Thoracic Society, and Centers
      for Disease Control and Prevention move in raising the amount of induration
      considered tuberculin positive to 15 mm in low-risk individuals?

PMID- 9596291
TI  - Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis
      patients.
AB  - BACKGROUND: Despite the use of directly observed therapy (DOT) by tuberculosis
      control programs, patient treatment failure, relapse, and acquired drug
      resistance remain problematic in a small number. We investigated serum drug
      levels in non-HIV-infected tuberculosis patients who were receiving DOT by the
      health department and did not respond to treatment as expected. METHODS: The
      indications for checking levels were as follows: (1) slow clinical response or
      failure to convert the sputum culture within 12 weeks; (2) treatment failure,
      early disease relapse < 13 months since being declared cured; (3) relapse, late
      disease reactivation > or = 13 months since being declared cured; and (4)
      acquired drug resistance while receiving DOT. Baseline characteristics of control
      subjects who responded to therapy as expected were compared. Venous blood for
      analysis was obtained at 2 h after directly observed ingestion and measured by
      high-performance liquid chromatography. RESULTS: Twenty-four patients receiving
      daily or twice-weekly standard therapy with isoniazid (INH, 300 or 900 mg) and
      rifampin (RMP, 600 mg) were identified; 22 had drug levels evaluated at 2 h. For
      INH, 15 of 22 patients (68%) had levels less than the reported target range. For
      RMP, 14 of 22 patients (64%) had low levels. Among the 14 patients receiving INH,
      900 mg, and RMP, 600 mg, 4 (29%) had very low levels of both. Use of a
      combination INH/RMP tablet was associated with lower INH levels (p=0.04);
      however, RMP levels were higher (p<0.02). Alcohol use was associated with
      significantly higher RMP (p<0.01) serum concentrations. CONCLUSIONS: Important
      questions remain concerning the utility and timing of serum drug measurements.
      However, if a patient is not responding to therapy as expected and one is assured
      that the Mycobacterium tuberculosis organism is susceptible to the drugs given
      and that the patient is taking the medication as prescribed, drug level
      monitoring should be considered.

PMID- 9596292
TI  - Effectiveness of a nosocomial tuberculosis control program at an urban teaching
      hospital.
AB  - STUDY OBJECTIVE: To assess the effectiveness of a nosocomial tuberculosis (TB)
      program at an urban teaching hospital. DESIGN: Retrospective review. SETTING: An
      urban teaching hospital, the University of California, San Diego Medical Center
      (UCSD), which cares for 25 to 30 culture-proven pulmonary TB cases (>80% of which
      are smear-positive) per year. STUDY POPULATION: Health-care workers.
      MEASUREMENTS: (1) Purified protein derivative (PPD) conversion rates. (2) Cases
      of active TB among health-care workers. (3) Compliance rates with isoniazid (INH)
      preventive therapy. RESULTS: The UCSD program was evaluated for the years 1993 to
      1995. The PPD conversion rate among established employees was 0.6%. Of 556
      employees who had an exposure, 494 (88.8%) were compliant with follow-up. Three
      hundred thirty-seven were skin-tested (the other 157 already had a known PPD >10
      mm). Only 2 of 337 (0.6%) converted. One case of active TB, unrelated to any
      documented hospital exposure, was discovered in 3 years among approximately 5,000
      employees per year (follow-up for convertors, 18 to 54 months). Only 48.4% of
      eligible employees completed at least 6 months of INH preventive therapy.
      CONCLUSIONS: UCSD's TB control measures appear to be effective in the prevention
      of nosocomial transmission of TB. Despite poor compliance with INH preventive
      therapy, cases of active TB among health-care workers were rare.

PMID- 9596293
TI  - Rapid diagnosis of tuberculosis in various biopsy and body fluid specimens by the
      AMPLICOR Mycobacterium tuberculosis polymerase chain reaction test.
AB  - STUDY OBJECTIVES: This study was undertaken to determine the usefulness of the
      AMPLICOR Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) test
      (Roche Diagnostic Systems, Inc; Branchburg, NJ) in diagnosing TB in tissue and
      body fluid specimens other than respiratory secretions. DESIGN AND SETTING:
      Prospective analysis of clinical and laboratory data in patients with suspected
      TB at the four divisional hospitals of Catholic Medical Center, located in New
      York. PATIENTS AND MEASUREMENTS: A total of 1,090 tissue and body fluid specimens
      from 1,032 patients with suspected TB were subjected to acid-fast bacillus (AFB)
      smear, culture, and the AMPLICOR MTB PCR test. RESULTS: Of the 1,090 specimens,
      32 grew M tuberculosis complex and 8 specimens grew isolates belonging to the
      Mycobacterium avium complex (MAC). The AMPLICOR MTB PCR test was positive for 24
      of the 32 specimens that grew M tuberculosis. It was also positive for four
      additional specimens that were culture-negative for M tuberculosis or MAC. Two of
      these specimens were from patients with a previously recorded positive sputum
      culture for M tuberculosis. The AMPLICOR test was negative for all eight
      specimens that yielded MAC only. When AMPLICOR MTB PCR test results were compared
      with the confirmed clinical diagnosis of TB, the sensitivity, specificity,
      positive predictive value, and negative predictive value for the AMPLICOR MTB PCR
      test were 76.4%, 99.8%, 92.8%, and 99.2%, respectively. PCR results were
      available within 6.5 hours, compared with an average of 3 weeks for culture of M
      tuberculosis. CONCLUSIONS: These data establish the utility of the AMPLICOR MTB
      PCR test for the rapid detection of M tuberculosis in tissue and body fluid
      specimens other than respiratory secretions.

PMID- 9596294
TI  - Comparative study of the clinical presentation of Legionella pneumonia and other
      community-acquired pneumonias.
AB  - The aim of this study was to compare the clinical, biological, and radiologic
      features of presentation in the emergency ward of community-acquired pneumonia
      (CAP) by Legionella pneumophila (LP) and other community-acquired bacterial
      pneumonias to help in early diagnosis of CAP by LP. Three hundred ninety-two
      patients with CAP were studied prospectively in the emergency department of a 600
      bed university hospital. Univariate and multivariate analyses were performed to
      compare epidemiologic and demographic data and clinical, analytical, and
      radiologic features of presentation in 48 patients with CAP by LP and 125
      patients with CAP by other bacterial etiology (68 by Streptococcus pneumoniae, 41
      by Chlamydia pneumoniae, 5 by Mycoplasma pneumoniae, 4 by Coxiella burnetii, 3 by
      Pseudomonas aeruginosa, 2 by Haemophilus influenzae, and 2 by Nocardia species.
      Univariate analysis showed that CAP by LP was more frequent in middle-aged, male
      healthy (but alcohol drinking) patients than CAP by other etiology. Moreover, the
      lack of response to previous beta-lactamic drugs, headache, diarrhea, severe
      hyponatremia, and elevation in serum creatine kinase (CK) levels on presentation
      were more frequent in CAP by LP, while cough, expectoration, and thoracic pain
      were more frequent in CAP by other bacterial etiology. However, multivariate
      analysis only confirmed these differences with respect to lack of underlying
      disease, diarrhea, and elevation in the CK level. We conclude that detailed
      analysis of features of presentation of CAP allows suspicion of Legionnaire's
      disease in the emergency department. The initiation of antibiotic treatment,
      including a macrolide, and the performance of rapid diagnostic techniques are
      mandatory in these cases.

PMID- 9596295
TI  - Implications for macrolide treatment in community-acquired pneumonia. Hopkins CAP
      Team.
AB  - STUDY OBJECTIVES: To identify associated clinical parameters, concurrent
      respiratory tract infections, and the association between macrolide-based therapy
      and mortality in patients with community-acquired pneumonia ascribed to atypical.
      DESIGN: Secondary analysis of prospective, cross-sectional study. SETTING:
      Tertiary care hospital. PATIENTS: Three hundred eighty-five consecutive patients
      who were admitted to the Johns Hopkins Hospital from November 11, 1990, through
      November 10, 1991, and treated for community-acquired pneumonia. RESULTS: An
      atypical pathogen was identified in 29 of 385 adults (7.5%). A second pathogen
      was detected in 16 of 29 patients (55.2%) in whom an atypical pathogen was
      detected, compared with 13 of 137 patients (9.5%) in whom conventional bacterial
      pathogens were detected (odds ratio, 10.22; 95% confidence interval, 3.7 to 28.8;
      p<0.0001). During hospitalization, only four patients (13.8%) with detection of
      an atypical pathogen received at least 7 days of either a macrolide or
      tetracycline. No patient identified to have an atypical pathogen died. For
      patients who either provided paired sera or who died, 24 of 197 (12.2%) had
      atypical pathogens detected. CONCLUSIONS: Despite vigorous study methods,
      atypical pathogens were uncommon in our hospitalized population. A second
      concurrent respiratory pathogen was identified for most patients with atypical
      pneumonia. Although macrolide use was rare in this patient population, mortality
      was zero for patients in whom an atypical pathogen was detected, affirming that
      macrolide-based therapy need not be routine in the therapeutic management of
      community-acquired pneumonia.

PMID- 9596296
TI  - Pneumococcal bacteremia in childhood: a 6-year experience in a community
      hospital.
AB  - OBJECTIVE: To review the clinical and laboratory findings in children with
      pneumococcal bacteremia during a 6-year period between 1989 and 1995. DESIGN:
      Retrospective review of medical records identified from computer-generated blood
      culture records. SETTING: Hurley Medical Center in Flint, Mich, a community
      teaching hospital affiliated with Michigan State University. MEASUREMENTS: Data
      concerning age, gender, race, clinical findings, laboratory features, nature of
      antibiotic therapy, source of bacteremia, and outcome were obtained from patient
      medical records. RESULTS: Most (68%) of the children with pneumococcal bacteremia
      were <2 years of age. About 50% of the cases of invasive pneumococcal disease in
      childhood occurred between February and May. Focal source of bacteremia was as
      follows: 11.5% had meningitis, 37% had pneumonia, 30% had otitis media, and 33%
      had no focal source. Overall, 60% of children were African-Americans, although in
      children with meningitis, whites were predominant (p<0.04). Leukocytosis was
      present in 81% and bandemia >1,500/microL was present in 53% of children. The
      overall mortality was 1.6% with a case fatality rate for meningitis of 14%.
      Penicillin resistance was found in 6.5% of pneumococcal isolates, although during
      1 study year (1993), 17% of all pneumococcal isolates from all sources in the
      same hospital were found to be penicillin resistant. CONCLUSIONS: Clinical and
      laboratory findings seen in children with pneumococcal bacteremia at a community
      hospital are presented with a review of literature. Pneumococci isolated from
      sterile body sites were found to be less resistant to antibiotics compared with
      those isolated from nonsterile body sites.

PMID- 9596297
TI  - Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii
      pneumonia.
AB  - STUDY OBJECTIVE: To examine the use of adjunctive corticosteroids in cases of
      severe Pneumocystis carinii pneumonia (PCP) in non-HIV-infected adult patients.
      DESIGN: Retrospective review of medical records. SETTING: Tertiary care urban
      teaching hospital. PATIENTS: Review identified 31 consecutive histologically
      confirmed primary cases of adult non-HIV-related PCP. Complete records were
      available for 30 patients, including 20 male and 10 female patients with a mean
      age of 58.3+/-15 years (+/-SD). Underlying conditions included organ
      transplantation (n=13), long-term immunosuppressive therapy (n=9), and
      chemotherapy for malignancy (n=8). All patients had documented PO2 <65 mm Hg or
      arterial oxygen saturation <90% on room air. INTERVENTIONS: Following the
      identification of P carinii, in addition to trimethoprim-sulfamethoxazole or
      pentamidine therapy, 16 patients received increased steroids (> or =60 mg
      prednisone daily equivalent; increased high-dose steroid group), whereas 14
      patients were maintained on a regimen of low doses (< or =30 mg prednisone
      equivalent daily) or had steroid therapy tapered (low-dose steroid group).
      RESULTS: The increased high-dose steroid group demonstrated a shorter required
      duration for mechanical ventilation (6.3+/-6 days vs 18.0+/-21 days; p=0.047), a
      shorter duration of ICU admission (8.5+/-7 days vs 15.8+/-8 days; p=0.025), and a
      shorter duration of supplemental oxygen use (10.0+/-4 vs 32.2+/-33; p=0.05). The
      hospital duration to discharge for the nine survivors in each group favored the
      use of corticosteroids (15.4+/-5 days vs 36.3+/-33 days; p=0.077). Similar rates
      were observed for intubation (75% vs 57%; p=0.442) and in-hospital mortality (44%
      vs 36%; p=0.722). CONCLUSIONS: These preliminary data suggest that high-dose
      adjunctive corticosteroids may accelerate recovery in cases of severe adult non
      HIV PCP.

PMID- 9596298
TI  - Pulmonary complications of HIV infection: autopsy findings.
AB  - STUDY OBJECTIVES: To describe the pulmonary complications in patients with HIV
      infection, and the changes in the incidence of these complications over a 12-year
      period. DESIGN: Retrospective review of autopsy records. SETTING: Two university
      affiliated medical centers. PATIENTS: We studied autopsy findings from 233
      patients with HIV infection who died between 1985 and 1996. Demographic data,
      risk factors for HIV infection, and the lengths of hospital stay were obtained.
      The histologic and microbiological findings of the respiratory system, and the
      extrapulmonary organ involvement by Kaposi's sarcoma (KS), Pneumocystis carinii,
      Mycobacterium tuberculosis, and Mycobacterium avium complex were reviewed.
      RESULTS: Ninety-two percent of the patients were black and 75% were male. The two
      most common identified risk factors for HIV infection were homosexuality (34%)
      and injection drug use (27%). Bacterial pneumonia was the most frequent pulmonary
      complication (42%). The two most common causes of bacterial pneumonia were
      Pseudomonas aeruginosa and Staphylococcus aureus. P carinii pneumonia (PCP) was
      found in 24%, with extrapulmonary involvement in 13%. Pulmonary mycobacterial
      infections were seen in 33%, with multiple extrapulmonary involvement. The most
      common site affected by KS was the lung. Of all pulmonary complications, only the
      incidence of PCP decreased over the 12-year period. CONCLUSIONS: Recognizing the
      high incidence rate of bacterial pneumonia, the high frequency of pulmonary KS
      and the not uncommon occurrence of extrapulmonary P carinii infection in patients
      with HIV helps in improving their care.

PMID- 9596299
TI  - Risk of death in cystic fibrosis patients with severely compromised lung
      function.
AB  - BACKGROUND: Lung disease accounts for most of the mortality in patients with
      cystic fibrosis (CF). Lung transplantation is an option for patients severely
      impaired, being recommended when life expectancy is estimated to be <2 years. Our
      objectives were to evaluate in our patient population the validity of currently
      accepted criteria for low life expectancy and to identify other potentially
      useful criteria. METHODS: Data were retrieved from CF patients followed up at our
      center who reached and kept an FEV1 <30% predicted. A life table was created and
      stratified according to characteristics believed to be of importance. In
      addition, the rate of decline in percent predicted FEV1 was analyzed. These
      characteristics were evaluated as predictors of risk of death. RESULTS: The
      median survival was 3.9 years (95% confidence interval, 2.88 to 4.12 years), with
      no significant differences according to gender, nutritional status, presence of
      diabetes, or decade in which the patient was cared for. Only by age was there a
      significant difference in the median survival (p<0.05). By proportional hazards
      regression, only the rate of decline in percent predicted FEV1 was a significant
      predictor of the risk of death, with a borderline effect from younger age
      (p=0.06). CONCLUSION: In our patient population, a cutoff value of FEV1 of < 30%
      predicted is not a reliable predictor of high risk of death within 2 years. The
      yearly rate of decline of percent predicted FEV1 is a better parameter to
      identify those patients at high risk for death.

PMID- 9596300
TI  - Allograft colonization and infections with pseudomonas in cystic fibrosis lung
      transplant recipients.
AB  - OBJECTIVE: To assess the incidence of pseudomonal infection, colonization, and
      inflammation in the allograft of lung transplant recipients with cystic fibrosis
      (CF) as compared with recipients with other end-stage lung disease. DESIGN:
      Retrospective review. SETTING: University medical center transplant service.
      PATIENTS: All patients with CF and chronic pseudomonal infection (n=62) and
      patients with nonseptic end-stage lung disease (n=52) receiving a double lung
      transplant between October 1983 and March 1996. RESULTS: Fifty lung transplant
      recipients with CF survived beyond postoperative day (POD) 15 and were subject to
      sequential bronchoscopy with BAL. Forty-four CF lung transplant recipients had
      Pseudomonas isolated from the allograft by median POD 15 as compared with 21 non
      CF lung transplant recipients (p<0.001) with isolation at median POD 158
      (p<0.0001). Thirteen CF lung transplant recipients had histologic evidence of
      infection when Pseudomonas was isolated as compared with only three of the non-CF
      lung transplant recipients (p<0.01). These infections occurred earlier in the CF
      lung transplant recipients (median POD 10 vs 261) (p<0.01). When compared with
      non-CF lung transplant recipients, CF lung transplant recipients with Pseudomonas
      isolated but without concomitant histologic infection (colonized) were
      demonstrated to have increased number of polymorphonuclear cells (PMNs) in the
      BAL fluid recovered from the allograft (17.66+/-24.94 x 10(6) cells vs 3.46+/
      4.73 x 10(6)) (p<0.05). Non-CF lung transplant recipients who became colonized
      with Pseudomonas also had a greater number of PMNs recovered when compared with
      non-CF lung transplant recipients who did not have Pseudomonas (22.32+/-34.00 x
      10(6) cells vs 0.21+/-0.18 x 10(6)) (p<0.01). Nine of 32 (28%) lung transplant
      recipients with CF have died from pseudomonal allograft infections, but this is
      no greater than 4 of 21 (19%) deaths related to Pseudomonas infection in
      recipients without CF (p=0.34). CONCLUSIONS: Isolation of Pseudomonas from the
      lung allograft occurs more frequently and earlier after transplantation in
      recipients with CF. While infections related to Pseudomonas also occur more
      frequently in recipients with CF, there is no increase in mortality. There is an
      intense inflammatory response in the lung allograft associated with the isolation
      of Pseudomonas in recipients with and without CF.

PMID- 9596301
TI  - Can chest CT decrease the use of preoperative bronchoscopy in the evaluation of
      suspected bronchogenic carcinoma?
AB  - BACKGROUND: Fiberoptic bronchoscopy (FOB) is frequently used to diagnose and
      stage bronchogenic carcinoma (BC). However, the value of FOB in diagnosis/staging
      BC presenting as a pulmonary nodule or mass (PNM) is controversial. Since chest
      CT is usually obtained in these patients, it may be used in patient selection for
      preoperative FOB. OBJECTIVE: Evaluation of the role of chest CT in determining
      the predictive value of FOB in diagnosing/staging a PNM, by comparing the results
      of CT and bronchoscopy. DESIGN: Retrospective review of chest CTs and medical
      records. PATIENTS: Consecutive patients with BC between 1992 and 1994 who had
      diagnostic FOB and CT in our institution, but without radiographic evidence of
      (1) pulmonary atelectasis, (2) endobronchial tumor or narrowing of the central
      airways, and (3) the PNM abutting the central airways. RESULTS: Sixty-four
      patients met the selection criteria. The size of the PNM ranged from 1.5 to 10
      cm; the size was < or = 4 cm in 62 patients. FOB provided a diagnosis in 22
      patients. Bronchoscopy detected endobronchial lesions in 11 patients (17%); 3 had
      lesions in more than one lobe. In three patients, the PNM was <3 cm. The
      radiographically undetected endobronchial tumor increased the tumor stage in only
      two patients. The "CT bronchus" sign had a positive and negative predictive value
      of 75% and 68%, respectively. CONCLUSIONS: (1) In this study, CT failed to detect
      endobronchial tumor in 11 of 64 patients (17%). Because of the implications of a
      new staging system, more studies are necessary before abandoning staging FOB. (2)
      The CT bronchus sign has a very high positive and negative predictive value in
      the use of diagnostic FOB and should be used to guide the method of biopsy of a
      PNM.

PMID- 9596302
TI  - Utility of CT scan evaluation for predicting pulmonary hypertension in patients
      with parenchymal lung disease. Medical College of Wisconsin Lung Transplant
      Group.
AB  - OBJECTIVE: To determine the utility of CT-determined main pulmonary artery
      diameter (MPAD) for predicting pulmonary hypertension (PH) in patients with
      parenchymal lung disease. DESIGN: Retrospective review of right-heart hemodynamic
      data and chest CT scans in 45 patients. SETTING: Tertiary-referral teaching
      hospital and VA hospital. PATIENTS: Between October 1990 and December 1995, 36
      patients referred for evaluation of parenchymal lung disease or possible
      pulmonary vascular disease were found to have PH, as defined by mean pulmonary
      artery pressure (mPAP) > or =20 mm Hg. Nine control patients (mPAP <20 mm Hg)
      were also identified (4 from hospital records search, 5 after evaluation for
      possible PH). RESULTS: CT-determined MPAD was 35+/-6 mm in patients with PH and
      27+/-2 mm in control subjects. In our group of patients, MPAD > or =29 mm had a
      sensitivity of 87%, specificity of 89%, positive predictive value (PPV) of 0.97,
      and positive likelihood ratio (LR) of 7.91 for predicting PH; in the subgroup of
      patients with parenchymal lung disease (n=28, PH and control subjects), MPAD > or
      =29 mm had a sensitivity of 84%, specificity of 75%, PPV of 0.95, and positive LR
      of 3.36 for predicting PH. The most specific findings for the presence of PH were
      both MPAD > or =29 mm and segmental artery-to-bronchus ratio > 1:1 in three or
      four lobes (specificity, 100%). There was no linear correlation between the
      degree of PH and MPAD (r=0.124). CONCLUSIONS: CT-determined MPAD has excellent
      diagnostic value for detection of PH in patients with advanced lung disease.
      Therefore, standard chest CT scans can be used to screen for PH as a cause of
      exertional limitation in patients with parenchymal lung disease. Because CT is
      commonly used to evaluate parenchymal lung disease, this information is readily
      available.

PMID- 9596303
TI  - Relationship of alveolar macrophage plasminogen activator and elastase activities
      to lung function and CT evidence of emphysema.
AB  - OBJECTIVE: To evaluate the relationship between alveolar macrophage (AM) elastase
      and plasminogen activator (PA) activities (considered to be potential
      pathogenetic factors in emphysema) and the development of emphysema in smokers.
      PARTICIPANTS: Thirty-four healthy smokers >35 years of age (mean+/-SD, 46+/-7
      years), with a mean+/-SD of 33+/-10 pack-years of smoking, who were recruited as
      volunteers. METHODS: Subjects had lung function testing and BAL to obtain AMs;
      limited high-resolution CT scans of the chest were obtained in 32 subjects to
      assess the presence of emphysema. Macrophage PA and elastase were determined
      using AM cultured on (131)I-fibrin-coated plates and 3H-elastin-coated plates,
      respectively. RESULTS: The number of AMs recovered per milliliter of BAL was
      significantly greater in the 16 subjects with CT evidence of mild emphysema than
      the 16 subjects without evidence of emphysema (669+/-301 x 10(3)/mL vs 414+/-268x
      10(3)/mL; p=0.01). There was no significant difference between AM elastase or PA
      activities in the 16 subjects with CT evidence of mild emphysema, when compared
      with the 16 subjects who had no CT evidence of emphysema (elastase, 2.72+/-1.35
      microg vs 2.49+/-0.91 microg elastin per 10(6) AMs per first 24 h; PA, 0.375+/
      0.126 vs 0.344+/-0.096 urokinase units/10(6) AMs). There was no significant
      correlation between levels of PA or elastase activities and FEV1, FEV1/FVC,
      forced expiratory flow rate between 25% and 75% of the FVC; PA activity but not
      elastase activity had a significant negative correlation (r=-0.47, p<0.01) with
      diffusion of carbon monoxide (DCO). The macrophage count in BAL had a significant
      negative correlation with DCO percent predicted (r=-0.61, p<0.001). CONCLUSIONS:
      The findings suggest that the number of AMs recovered per milliliter of BAL
      (presumably indicating the number in the alveolar spaces) is related to the
      development of emphysema in smokers as indicated by CT scan of the chest and DCO.
      The results also suggest that the level of PA enzyme activity in AMs may be a
      pathogenetic factor in the decrease in DCO in smokers.

PMID- 9596304
TI  - Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler:
      a double-blind, placebo-controlled study in adults with moderate-to-severe
      chronic asthma. Pulmicort Turbuhaler Study Group.
AB  - OBJECTIVE: To determine the ability of budesonide via an inhaler (Pulmicort
      Turbuhaler; Astra Draco AB) to replace oral glucocorticosteroids (GCSs) in adult
      subjects with moderate-to-severe asthma. DESIGN: Double-blind, randomized, and
      placebo-controlled study, with parallel groups. SETTING: Multicenter study in
      outpatient setting. PARTICIPANTS: Eighty men and 79 women, aged 20 to 69 years,
      with moderate-to-severe asthma and a mean FEV1 of 58.3% predicted normal. All
      subjects were receiving oral GCS treatment and 79% of subjects were also
      receiving inhaled beclomethasone dipropionate (BDP). The mean daily doses of
      prednisone at baseline, including converted dose of BDP, for the placebo,
      budesonide 400 microg, and budesonide 800 microg, respectively, were 19.7 mg,
      19.5 mg, and 18.7 mg. MEASUREMENTS AND INTERVENTIONS: After a 2-week baseline
      period, subjects entered a 20-week treatment period, during which the oral dose
      of prednisone was reduced by forced down-titration at 2-weekly intervals.
      RESULTS: Subjects receiving 400 microg or 800 microg bid of budesonide achieved a
      significantly greater reduction (82.9% and 79.0% respectively) in oral GCS dose
      compared with placebo-treated subjects (27%; p<0.001). Two thirds of the subjects
      receiving budesonide were able to achieve sustained oral corticosteroid
      cessation, compared with 8% in the placebo group. Additionally, both doses of
      budesonide resulted in significant improvement in results of pulmonary function
      tests and asthma symptoms scores, and a significant decrease in the use of
      bronchodilator therapy. The mean plasma cortisol levels before and after
      adrenocorticotropic hormone stimulation increased most toward the normal range in
      the budesonide-treated groups compared with placebo-treated subjects. CONCLUSION:
      Budesonide administered via Turbuhaler has a significant oral GCS-sparing
      capacity with maintained or improved asthma control in adult subjects with
      moderate-to-severe asthma.

PMID- 9596305
TI  - Short-term cardiovascular effects of salmeterol.
AB  - The occurrence of cardiovascular side effects is sometimes associated with the
      utilization of beta-adrenoceptor agonists. The most important causes of these
      undesirable pharmacologic actions are as follows: (1) direct stimulation of
      cardiac beta-adrenoceptors; (2) reflex activation of adrenergic mechanisms due to
      peripheral vasodilation; (3) hypokalemia; and (4) hypoxemia. The aim of this
      study was to evaluate the potential short-term, cardiovascular side effects of
      salmeterol, a long-acting and highly selective beta2-adrenoceptor agonist. Eight
      volunteer healthy subjects and eight patients with reversible airway obstruction
      and without cardiovascular alterations were treated with 50 microg of salmeterol
      twice a day for 3 days and then with 100 microg of salmeterol twice a day for a
      further 3-day period. The 24-h ECG (Holter) monitoring and measurement of
      arterial BP, performed on the admission day and on the third and the sixth day of
      pharmacologic treatment, showed that salmeterol did not produce any significant
      change in mean heart rate, number of supraventricular and ventricular premature
      complexes, and BP. Furthermore, no ECG abnormality related to myocardial ischemia
      was recorded during 24-h Holter monitoring. These data suggest that salmeterol,
      administered in regular and high doses for a short period, does not cause
      significant cardiovascular effects in both normal subjects and patients with
      reversible airway obstruction.

PMID- 9596306
TI  - Race, income, urbanicity, and asthma hospitalization in California: a small area
      analysis.
AB  - STUDY OBJECTIVES: To explicate the interrelationship between asthma
      hospitalization and race/ethnicity and income. DESIGN: Small area ecologic
      analysis using census and administrative data. SETTING AND PARTICIPANTS: All
      asthma hospitalizations in California were identified using the 1993 California
      Hospital Discharge file. Small area analyses of Los Angeles (LA) were compared
      with published rates in New York City (NYC). RESULTS: In 1993, the age-adjusted
      asthma hospitalization rate in California for nonelderly blacks was 42.5/10,000
      approximately four times higher than other populations. Black rates remained
      fourfold higher after stratification by age, income, and urbanicity. Multivariate
      analyses suggest that the association between black race and asthma
      hospitalization is independent of income. Regardless of race, children and
      persons living in poverty were at increased risk for asthma hospitalization.
      Urbanicity was not a predictor for asthma hospitalization. Overall, asthma
      hospitalization rates in NYC were 2.8 times higher compared with rates in LA;
      while rates were similar among blacks (60 vs 40/10,000, respectively), Puerto
      Rican Hispanics in NYC had dramatically higher rates compared with Mexican
      Hispanics in LA (63 vs 14/10,000, respectively). CONCLUSIONS: After controlling
      for socioeconomic status, notable differences in asthma hospitalization by race
      and ethnicity persist. The reasons for the significantly elevated risk of asthma
      morbidity among blacks remain unclear.

PMID- 9596307
TI  - Respiratory complications after coronary artery bypass surgery with unilateral or
      bilateral internal mammary artery grafting.
AB  - BACKGROUND AND STUDY OBJECTIVE: Use of bilateral internal mammary artery (IMA)
      grafts during coronary artery revascularization procedures carries the potential
      for increased incidence of postoperative respiratory complications compared with
      use of unilateral IMA grafts. The purpose of this study was to compare the
      incidence of respiratory complications such as hypoxemia, atelectasis, pleural
      effusion, and diaphragmatic dysfunction in patients who received one or both IMAs
      as conduit grafts. DESIGN: Prospective, comparative study. SETTING: Surgical ICU
      at a tertiary teaching hospital. PATIENTS: Seventy-five patients with bilateral
      and 75 patients with unilateral IMA grafts. MEASUREMENTS: Serial postoperative
      PaO2/fraction of inspired oxygen measurements, radiographic scores of atelectasis
      and pleural effusion, duration of mechanical ventilation, length of ICU and
      hospital stay, and incidence of pneumothorax, pneumonia, and wound infection.
      RESULTS: There was a higher incidence (51% vs 25%; p=0.002) and severity (0.48+/
      0.09 vs 0.15+/-0.05 on the first postoperative day, 0.39+/-0.07 vs 0.27+/-0.07 on
      the fourth postoperative day, mean+/-SEM; p=0.004) of postoperative right lower
      lobe atelectasis in the group who received bilateral IMA grafts than in those who
      received left IMA grafts. This finding probably reflects the effects of
      additional surgical intervention on the right side of the chest. Incidence and
      severity of pleural effusion, gas exchange impairment, duration of mechanical
      ventilation, ICU and hospital stay, and incidence of pneumothorax, pneumonia, and
      wound infection were not influenced by use of bilateral IMA grafts (p>0.05).
      CONCLUSION: We conclude that use of bilateral IMA grafts during coronary artery
      revascularization does not increase the incidence of postoperative respiratory
      complications compared with unilateral IMA grafting.

PMID- 9596308
TI  - Systemic inflammation present in patients undergoing CABG without extracorporeal
      circulation.
AB  - STUDY OBJECTIVES: This study was conducted to evaluate to what extent the
      cardiopulmonary bypass (CPB) procedure in patients undergoing coronary artery
      bypass grafting (CABG) contributes to the systemic inflammatory response.
      Therefore, we measured bactericidal permeability increasing protein (BPI) as an
      indicator of neutrophil activation, interleukin 6 as inducer of the acute phase
      response, and lipopolysaccharide binding protein and C-reactive protein as
      parameters of the acute phase response in patients undergoing CABG either with or
      without the use of CPB. DESIGN: Prospective study. SETTING: Cardiopulmonary
      surgery department in a university hospital. PATIENTS: Sixteen patients
      undergoing elective CABG were included. Eight patients underwent surgery with
      CPB, and eight patients underwent surgery without CPB (non-CPB). INTERVENTIONS:
      In the CPB group, blood samples were taken upon induction of anesthesia, at the
      start of aortic cross-clamping, at aortic unclamping, and 0.5, 4, 8, and 18 h
      thereafter. In the non-CPB group, blood samples were taken upon induction of
      anesthesia, and 0.5, 4, 8, and 18 h after completion of the bypass graft
      anastomoses. MEASUREMENTS AND RESULTS: BPI release from neutrophil granules
      markedly increased during surgery in CPB patients but not in non-CPB patients.
      The increase in acute phase reactants, however, was the same in both patient
      groups. CONCLUSIONS: These data indicate that the acute phase response in CABG
      patients, which has historically been ascribed to the CPB procedure, is
      predominantly caused by the surgical procedure per se. Early neutrophil
      activation, however, is seen only when extracorporeal circulation is used.

PMID- 9596309
TI  - Clinical evaluation of the Physio annuloplasty ring.
AB  - STUDY OBJECTIVES: Prospective evaluation of a selectively flexible annuloplasty
      ring was undertaken to assess its safety and efficacy. PATIENTS: Between December
      1992 and November 1996, 190 patients with mitral regurgitation underwent mitral
      valve repair using an annuloplasty ring (Carpentier-Edwards Physio; Baxter
      Edwards CVS Laboratories; Irvine, Calif). Ninety-four were in New York Heart
      Association class I or II. Etiology was degenerative in 74% of the patients.
      RESULTS: Four patients died early for a hospital mortality of 2.1%, and one late
      death occurred. Two patients with systolic anterior motion required early valve
      replacement. Two transient episodes of hemiparesis occurred during the first
      postoperative month. There were no late thromboembolic complications, no late
      reoperation, and no endocarditis. Mean follow up of 23+/-13 months was complete
      in 99% of the patients. Seventy-seven patients (40.5%) have had Doppler
      echocardiography > 1 year after surgery: 61 (80%) of them have no residual
      regurgitation, 15 have grade 1+/4+ mitral regurgitation, while 1 has grade 2+/4+
      insufficiency. Left ventricular end-diastolic volume index (mL/lm2) decreased
      from 107.4+/-35.5 preoperatively to 74.2+/-24.4 at last control (p<0.001).
      CONCLUSION: The physio annuloplasty ring provided reliable and stable results at
      medium-term follow-up with a very low incidence of valve-related complications.

PMID- 9596310
TI  - Cytologically proved malignant pleural effusions: distribution of transudates and
      exudates.
AB  - PURPOSE: This study attempts to determine the distribution of transudates vs
      exudates in pathologically proved malignant pleural effusions and the necessity
      for cytologic studies in patients with a transudative effusion. MATERIALS AND
      METHODS: A retrospective review of all cytologically positive malignant pleural
      effusions was performed at Duke University Medical Center over an 18-month
      period. All effusions were characterized as a transudate or an exudate based on
      standard criteria, including lactate dehydrogenase and protein values. RESULTS:
      Ninety-eight patients with a mean age of 62 years were identified as having a
      cytologically positive malignant pleural effusion and blood chemistry values
      available to distinguish an exudate from transudate. Ninety-seven patients (99%,
      95% confidence interval; 0.94 to 0.99) had criteria for an exudative effusion.
      One patient (1%) with diffuse metastatic lung cancer had a borderline transudate
      and was in congestive heart failure at the time of thoracentesis. CONCLUSIONS:
      Cytologically positive pleural effusions for malignancy are almost always
      exudates. Cytologic evaluation for malignant cells of a transudative pleural
      effusion is not recommended.

PMID- 9596311
TI  - Sclerotherapy for malignant pleural effusions: a prospective randomized trial of
      bleomycin vs doxycycline with small-bore catheter drainage.
AB  - BACKGROUND: Malignant pleural effusions are a common problem for patients with
      metastatic disease. Most patients are treated with tube thoracostomy and
      sclerotherapy, although there remains no standard approach. The purpose of this
      study was to compare the efficacy of bleomycin with doxycycline sclerotherapy for
      the treatment of malignant pleural effusions using small-bore catheters. METHODS:
      All patients with a symptomatic malignant pleural effusion referred for chest
      tube drainage and sclerotherapy over a 2-year period were considered eligible.
      Using image guidance, a 14F self-retaining catheter was inserted into the pleural
      space and connected to continuous wall suction. When drainage fell below 200
      mL/d, patients were randomized to 60 U of bleomycin or 500 mg of doxycycline
      sclerotherapy. Response at 30 days was determined. RESULTS: One hundred six
      patients were enrolled in the study. Fifteen men (29%) and 37 women (71%) with a
      mean age of 57 years received bleomycin sclerotherapy. Twenty-one of the 29
      patients (72%) alive and evaluable at 30 days had successful sclerotherapy.
      Twenty-three men (43%) and 31 women (57%) with a mean age of 61 years received
      doxycycline sclerotherapy. Twenty-three of the 29 patients (79%) alive and
      evaluable at 30 days had successful sclerotherapy. There was no significant
      difference in response rates between doxycycline and bleomycin (p=0.760).
      CONCLUSIONS: These data continue to support a role for small-bore chest drainage
      and sclerotherapy, although there was no significant difference in 30-day
      response rates between doxycycline and bleomycin.

PMID- 9596312
TI  - Respiratory changes due to long-term exposure to urban levels of air pollution: a
      histopathologic study in humans.
AB  - STUDY OBJECTIVES: To evaluate the potential associations between long-term
      exposure to air pollution and histopathologic evidence of damage to the lungs in
      humans. DESIGN: Lung tissue samples were collected during necropsies of
      individuals who died due to violent causes, selected on the basis of their
      exposure background. PATIENTS: The exposed group was composed of individuals who
      lived in Guarulhos, an area with high mean levels of inhalable particles. The
      control group was composed of individuals who lived in two cities with economies
      based on agricultural activities: Ribeirao Preto and Ourinhos. INTERVENTIONS:
      Information about cigarette smoking and occupational exposure was obtained from
      family members. MEASUREMENTS AND RESULTS: Morphometric evaluation of the main
      bronchus was conducted to determine the volume ratio of submucosal glands.
      Histopathologic alterations of the bronchioli were evaluated by scoring the
      presence of inflammatory reaction, wall thickening, and secretory hyperplasia.
      The number of spots of carbon deposition was counted along the regions of
      lymphatic drainage (visceral pleura and axial connective tissue around bronchi
      and blood vessels). Statistical analysis was done by means of regression models
      controlled for age, smoking, and occupational exposure. Lungs collected from the
      high pollution area presented evidence of more histopathologic damage in
      comparison to those from the clean environments. These effects were observed even
      after controlling for individual differences in age, sex, and cigarette smoking
      levels. CONCLUSIONS: These results suggest that long-term exposure to air
      pollution may contribute to the pathogenesis of airway disease, and that urban
      levels of air pollution have adverse effects on the respiratory tract.

PMID- 9596313
TI  - The influence of gender on cough reflex sensitivity.
AB  - BACKGROUND: The more common occurrence in women of cough due to angiotensin
      converting enzyme inhibitors raises the possibility of gender-related differences
      in the sensitivity of the cough reflex. Of two recent studies that evaluated
      cough response to inhaled capsaicin in normal subjects, one demonstrated
      heightened sensitivity of the cough reflex in women compared with men, while the
      other revealed no gender-related differences. To further investigate this
      question, we reviewed our experience with cough challenge testing in normal
      volunteers. STUDY OBJECTIVE: To compare cough reflex sensitivity in healthy adult
      female and male subjects. DESIGN: Retrospective data analysis. SETTING: Academic
      medical center. PARTICIPANTS: One hundred healthy volunteers (50 male, 50
      female). INTERVENTIONS: Subjects inhaled capsaicin in ascending, doubling
      concentrations until the concentration inducing five or more coughs (C5) was
      reached. In addition, the concentration inducing two or more coughs (C2; cough
      threshold) was measured. RESULTS: Mean log C5 was significantly lower in women
      than in men: 1.02+/-0.09 (SEM) microM vs 1.41+/-0.08 microM, respectively
      (p=0.002). Log C2 (cough threshold) was also significantly lower in female
      subjects: 0.534+/-0.068 microM vs 0.870+/-0.065 microM in male subjects
      (p=0.00058). CONCLUSION: Healthy women have a more sensitive cough reflex than do
      healthy men. The reasons for this significant gender difference remain to be
      elucidated, but may involve a heightened sensitivity, in women, of the sensory
      receptors within the respiratory tract that mediate cough.

PMID- 9596314
TI  - Pediatric reference values for respiratory resistance measured by forced
      oscillation.
AB  - OBJECTIVES: To determine, in North American children, reference values for
      respiratory resistance measurements by the forced oscillation (Rfo) technique and
      to examine whether sitting height, as index of truncal length, is a better
      determinant of resistance, less influenced by race and gender, than standing
      height. DESIGN/SETTING: A prospective cross-sectional study of healthy nonobese
      children, carefully selected for absence of atopy, exposure to tobacco smoke, and
      recent upper respiratory tract infection. MEASUREMENTS: Three measurements of
      respiratory resistance by forced oscillation were obtained at the fixed
      frequencies of 8 Hz (Rfo8), 12 Hz (Rfo12), and at 16 Hz (Rfo16) using the Custo
      Vit R (Custo Med GMBH; Munich, Germany). In cooperative children, routine
      spirometry (FEV1, FVC, and peak expiratory flow rate [PEFR]) was also performed.
      RESULTS: We recruited 217 healthy children aged 3 to 17 years. Reproducible
      measurements of Rfo8 were obtained for 206 children, Rfo12 for 197 children, and
      Rfo16 for 209 children. Normal FEV1, FVC, and PEFR values were documented in all
      69 subjects who were able to reproducibly cooperate with spirometry. Multiple
      linear regression identified measurements of either sitting or standing height as
      the best, and equally strong, determinants of respiratory resistance at all three
      frequencies. Gender and race were not important factors once either sitting or
      standing height measurement was considered. Our regression equations at 8 Hz are
      comparable to published reference values obtained at fixed frequencies of 6, 8,
      and 10 Hz using other instruments. However, in comparison to our results, prior
      values tended to underestimate resistance in the shortest children or to
      overestimate it in the tallest ones. Our regression equation for Rfo12 is similar
      to the only previously published one, while no reference values at 16 Hz were
      available for comparison. CONCLUSIONS: Height is the best predictor for total
      respiratory resistance at 8, 12, and 16 Hz in children aged > or = 3 years. Use
      of sitting height does not appear to be a stronger determinant of resistance than
      standing height.

PMID- 9596315
TI  - Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase
      I. rhDNase Study Group.
AB  - STUDY OBJECTIVE: To study the safety and efficacy of aerosolized recombinant
      human DNase I in the treatment of idiopathic bronchiectasis. DESIGN: Double
      blind, randomized, placebo-controlled, multicenter study. POPULATIONS: Three
      hundred forty-nine adult outpatients in stable condition with idiopathic
      bronchiectasis from 23 centers in North America, Great Britain, and Ireland.
      INTERVENTIONS AND MEASUREMENTS: Study patients received aerosolized rhDNase or
      placebo twice daily for 24 weeks. Primary end points were incidence of pulmonary
      exacerbations and mean percent change in FEV1 from baseline over the treatment
      period. RESULTS: Pulmonary exacerbations were more frequent and FEV1 decline was
      greater in patients who received rhDNase compared with placebo during this 24
      week trial. CONCLUSIONS: rhDNase was ineffective and potentially harmful in this
      group of adult outpatients in stable condition with idiopathic bronchiectasis.
      This contrasts with previously published results that demonstrated efficacy of
      rhDNase in patients with cystic fibrosis bronchiectasis.

PMID- 9596316
TI  - Effects of tracheal suctioning on respiratory resistances in mechanically
      ventilated patients.
AB  - OBJECTIVE: To evaluate the effects of tracheal suctioning (TS) on respiratory
      resistances in sedated critical care patients receiving mechanical ventilation
      (MV). SETTING: Surgical ICU of Bichat Hospital, Paris. PATIENTS AND PARTICIPANTS:
      Thirteen sedated critical care patients receiving MV for various conditions.
      MEASUREMENTS AND RESULTS: Airway resistances (R1), airway and pulmonary
      resistances (R2), and intrinsic positive end-expiratory pressure (PEEPint) were
      measured according to the end-inspiratory and end-expiratory occlusion methods
      before and after TS. R1 and R2 increased by 49.1% and 46.3%, respectively, 0.5
      min after TS (p<0.01) but returned to baseline values at 1 min without any change
      thereafter. PEEPint decreased progressively following TS to reach a significant
      level (-13.3%) at 10 min (p<0.05) and was persistently reduced at 30 min
      (p<0.01). Nine patients received 500 microg of inhaled albuterol before another
      suctioning procedure. R1 and R2 decreased by 11.5% and 9.9%, respectively, 20 min
      after inhalation (p<0.05), but the R1 and R2 initial increase following TS did
      not differ between the two suctioning procedures. CONCLUSIONS: TS evokes only a
      transient bronchoconstrictor response, but thereafter, does not reduce
      respiratory resistances below presuctioning values. However, the decrease of
      PEEPint following TS suggests an increase of expiratory flow. Effective beta2
      adrenergic receptor blockade fails to suppress the TS-induced bronchoconstrictor
      response.

PMID- 9596317
TI  - The use of noninvasive positive pressure ventilation in the emergency department:
      results of a randomized clinical trial.
AB  - OBJECTIVE: To determine whether the use of noninvasive positive pressure
      ventilation (NPPV) in the emergency department (ED) will reduce the need for
      tracheal intubation and mechanical ventilation. DESIGN: Randomized, controlled,
      prospective clinical trial. SETTING: ED of Barnes-Jewish Hospital, a university
      affiliated teaching hospital. PATIENTS: Twenty-seven patients meeting a
      predetermined definition of acute respiratory distress requiring hospital
      admission. INTERVENTIONS: Conventional medical therapy for the various etiologies
      of acute respiratory distress and the application of NPPV. MEASUREMENTS AND
      RESULTS: The primary outcome measure was the need for tracheal intubation and
      mechanical ventilation. Secondary outcomes also assessed included hospital
      mortality, hospital length of stay, acquired organ system derangements, and the
      utilization of respiratory care personnel. Sixteen patients (59.3%) were randomly
      assigned to receive conventional medical therapy plus NPPV, and 11 patients
      (40.7%) were randomly assigned to receive conventional medical therapy without
      NPPV. The two groups were similar at the time of randomization in the ED with
      regard to demographic characteristics, hospital admission diagnoses, and severity
      of illness. Tracheal intubation and mechanical ventilation was required in seven
      patients (43.8%) receiving conventional medical therapy plus NPPV and in five
      patients (45.5%) receiving conventional medical therapy alone (relative
      risk=0.96; 95% confidence interval=0.41 to 2.26; p=0.930). There was a trend
      towards a greater hospital mortality rate among patients in the NPPV group (25%)
      compared to patients in the conventional medical therapy group (0.0%) (p=0.123).
      Among patients who subsequently required mechanical ventilation, those in the
      NPPV group had a longer time interval from ED arrival to the start of mechanical
      ventilation compared to patients in the conventional medical therapy group
      (26.0+/-27.0 h vs 4.8+/-6.9 h; p=0.055). CONCLUSIONS: We conclude that the
      application of NPPV in the ED may delay tracheal intubation and the initiation of
      mechanical ventilation in some patients with acute respiratory distress. We also
      demonstrated that the application of NPPV was associated with an increased
      hospital mortality rate. Based on these preliminary observations, larger clinical
      investigations are required to determine if adverse patient outcomes can be
      attributed to the early application of NPPV in the ED. Additionally, improved
      patient selection criteria for the optimal administration of NPPV in the ED need
      to be developed.

PMID- 9596318
TI  - Assessment of three methods to reduce the influence of mathematical coupling on
      oxygen consumption and delivery relationships.
AB  - STUDY OBJECTIVES: To determine if oxygen consumption/oxygen delivery (VO2/DO2)
      relationships derived using calorimetry (which are not influenced by shared
      measurement error) agreed with those obtained using the pulmonary artery (PA)
      catheter alone. To evaluate three strategies to reduce the influence of shared
      measurement error to determine if agreement between the two methods could be
      improved. METHODS: Twenty-seven patients were studied following coronary artery
      bypass surgery. Calorimetric VO2, six thermodilution cardiac outputs (COs), and
      arterial and mixed venous oxygen content measurements were made at baseline and
      were repeated 30 min following dobutamine administrations of 3 microg/kg/min and
      5 microg/kg/min. RESULTS: Dobutamine produced a dose-dependent increase in DO2,
      from 378+/-65 mL/min/m2 to 446+/-78 mL/min/m2 (p<0.01) and in both PA catheter
      and calorimetric-derived VO2, from 104+/-18 mL/min/Mi2 to 114+/-22 mL/min/m2
      (p<0.05) and from 117+/-15 mL/min/m2 to 126+/-19 mL/min/m2 (p<0.01),
      respectively. Agreement was poor (bias=12%, SD=21%) between the calorimetric and
      PA catheter methods of determining VO2/DO2 slope. When three CO measurements were
      used to calculate VO2, and three separate CO measurements were used to calculate
      DO2, the level of agreement between the two methods improved (bias=2%, SD=15%).
      Increasing the number of COs resulted in a similar improvement in the level of
      agreement between the two methods. Weighting the slope to the observed change in
      DO2 was the best method to improve the level of agreement (bias=2%, SD=6% for
      three COs). CONCLUSIONS: To reduce the influence of shared measurement error, the
      best strategy to improve the measurement of VO2/DO2 slope is to maximize the
      change in DO2 (optimally over 100 mL/min/m2).

PMID- 9596319
TI  - Protective effects of ischemic preconditioning on donor lung in canine lung
      transplantation.
AB  - BACKGROUND: Myocardial ischemic preconditioning has been found to protect the
      myocardium. We hypothesized that lung ischemic preconditioning might enhance
      canine lung preservation and reduce allograft lung dysfunction after
      transplantation. METHODS: Ten pairs of adult canines underwent left lung
      allotransplantation. Five donors were treated with ischemic preconditioning
      (their left hilus clamped for 10 min and released for 15 min [group IP]), and
      five donors were not treated with ischemic preconditioning (group C). The donor
      lungs were flushed with 4 degrees C Euro-Collins solution (ECS) and stored in the
      same solution for 2 1/2 h, then transplanted to the recipient canines. The
      animals were observed for 1 to 2 h after transplantation. The lung venous blood
      of the recipient and donor lung tissue was collected just after thoracotomy and 1
      h after reperfusion of the transplanted lung in both groups. RESULTS: The numbers
      of polymorphonuclear leukocytes (PMNs) in the pulmonary venous blood after
      reperfusion were significantly higher in group IP than in group C (p<0.05).
      However, the numbers of PMNs in lung interstitium under microscopy were less in
      group IP than in group C. The thromboxane B2, malondialdehyde, and mean pulmonary
      artery pressure contents were significantly lower in group IP than in group C
      (p<0.05), and the superoxide dismutase and mixed venous oxygen tension values
      were significantly higher in group IP than in group C (p<0.05). Histologic
      findings show less damage in group IP than in group C. CONCLUSIONS: The
      protective effects of ischemic preconditioning in conjunction with ECS flush and
      storage were superior to using ECS alone. The possible mechanisms were that
      ischemic preconditioning inhibited the accumulation and activation of PMNs in
      lung tissue and reduced the production of oxygen-free radicals.

PMID- 9596320
TI  - The therapeutic potential of nitric oxide in lung transplantation.
AB  - Endogenously produced oxides of nitrogen appear to play important roles in tissue
      and organ homeostasis. Endogenous production of nitric oxide, which can be
      altered in response to various stimuli, can modulate vascular tone, oxyradical
      cascades, cell adhesion, and other aspects of inflammation. Because exogenously
      administered (inhaled) nitric oxide can mediate pulmonary vasodilatation and
      improve pulmonary function in some patients with lung injury, treatment of lung
      allograft recipients with inhaled nitric oxide may ameliorate ischemia
      reperfusion injury, thereby improving perioperative pulmonary function and
      diminishing ventilatory support requirements. This review examines the biology of
      nitric oxide and present data that support its potential therapeutic effects for
      lung transplant recipients.

PMID- 9596321
TI  - Pathophysiology of cardiac tamponade.

PMID- 9596322
TI  - The assault on the Swan-Ganz catheter: a case history of constrained technology,
      constrained bedside clinicians, and constrained monetary expenditures.

PMID- 9596323
TI  - A randomized comparison of exercise training in patients with normal vs reduced
      ventricular function.
AB  - BACKGROUND: Exercise training is recommended after myocardial infarction (MI) or
      bypass surgery in order to improve exercise tolerance. In some patients, the
      decrement in exercise capacity secondary to deconditioning and the left
      ventricular stunning associated with MI or coronary artery bypass graft (CABG)
      spontaneously improves after the event. However, the impact of the status of the
      left ventricle on these improvements is unknown. METHODS: Sixty-seven patients 1
      month after MI or CABG were randomized to a training (n=34; age, 59+/-7 years) or
      a control group (n=33; age, 55+/-6 years). Forty-two patients had an ejection
      fraction >50% (22 in the training group and 20 in the control group), and 25
      patients had an ejection fraction <40% (12 in the exercise group and 13 in the
      control group). After stabilization for approximately 1 month after the event,
      patients in the exercise group underwent 8 weeks of twice daily exercise at a
      residential rehabilitation center, while control patients received usual care.
      Initially and after 8 weeks, patients in both groups underwent maximal exercise
      testing with gas exchange and lactate analysis. RESULTS: Exercise training
      increased peak oxygen consumption (VO2) only in the reduced ejection fraction
      group (19.4+/-3.0 to 23.9+/-4.8 mL/kg/min; p<0.05); the exercise group with
      normal ventricular function did not change significantly. Changes in VO2 at the
      lactate threshold paralleled those of peak VO2 for both groups. Conversely,
      control patients with normal ventricular function increased peak VO2
      spontaneously (20.8+/-3.9 to 24.8+/-3.5 mL/kg/min; p<0.01), whereas control
      patients with reduced ventricular function did not improve peak VO2. CONCLUSION:
      These data suggest that patients with depressed left ventricular function
      strongly benefit from rehabilitation, whereas most patients with preserved left
      ventricular function following MI or CABG tend to improve spontaneously 1 to 3
      months after the event.

PMID- 9596324
TI  - The role of atropine premedication in fiberoptic bronchoscopy using intravenous
      midazolam sedation.
AB  - OBJECTIVE: Atropine premedication is widely used for fiberoptic bronchoscopy and
      may help by drying secretions, producing bronchodilatation, or preventing
      vasovagal reactions. The objective of this study was to see whether atropine
      premedication is really of practical benefit when patients are sedated with i.v.
      midazolam. DESIGN: In a double-blind study, patients were randomly allocated to
      receive i.m. atropine (0.6 mg) or saline placebo (1 mL) as premedication 30 to 60
      minutes before they were sedated with progressive doses of i.v. midazolam until
      judged to be lightly asleep. SETTING: A District General Hospital in England.
      PARTICIPANTS: One hundred consecutive patients referred for bronchoscopy.
      MEASUREMENTS AND RESULTS: Samples taken during the procedure were washings for
      microbiology and cytology and brushings for cytology and biopsy, but no
      transbronchial biopsies. Peak flow readings were recorded before premedication
      and before the start of the procedure. During the procedure an estimate was made
      of pharyngeal and tracheobronchial secretions, bleeding, use of saline to wash
      out secretions, and local anesthetic needed to control coughing. Patients were
      monitored for saturation and cardiac rhythm. There was no significant
      bronchodilatation after premedication in either group, nor were there differences
      in secretions, use of saline, tracheobronchial bleeding, desaturation, and
      arrhythmias. More local anesthetic was needed to control coughing in the placebo
      group (mean 357 mg vs 331 mg in the atropine group, p=0.02), but this was not of
      practical significance. CONCLUSION: When intravenous midazolam sedation is used
      for bronchoscopy, atropine premedication is not of benefit.

PMID- 9596325
TI  - Chronic mitral regurgitation: when and how to operate.

PMID- 9596326
TI  - The value of the Nd:YAG laser for the surgery of lung metastases in a randomized
      trial.
AB  - OBJECTIVE: A prospective randomized trial was established in our department to
      compare the usefulness of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser in
      resection of lung metastases. We report the results of the first 45 patients
      after a minimum of 2 years of follow-up. DESIGN: Randomized prospective trial
      from March 1987 to March 1995. SETTING: University teaching hospital. PATIENTS:
      Forty-five patients underwent resection for pulmonary metastases with two
      different techniques chosen at random: 23 patients were treated with an Nd:YAG
      laser (group A) and 22 patients with a traditional diathermic device (group B).
      INTERVENTIONS: A total of 71 pulmonary lesions were resected by minimal excision,
      41 by laser and 30 by diathermy. Sixty-three lesions were diagnosed as active
      metastases from various sites. RESULTS: No deaths occurred during surgery. Eight
      patients (6 in group B) developed minor complications. In two patients from group
      B, lesions recurred at the resection site. The use of Nd:YAG laser was not
      associated with a significantly longer survival (log rank test, p=0.49). Laser
      resection allowed more tissue sparing (mean ratio lesion diameter/volume
      resected, 0.94 vs 1.11, p<0.008). Univariate and multivariate analyses revealed
      the importance of laser use in reducing the number of days of postoperative air
      leakage (3.91 vs 5.00 days) and hospital stay (7.50 vs 9.90 days). CONCLUSIONS:
      Laser use significantly reduced tissue loss, postoperative air leakage, and
      hospital stay. Influence on long-term survival was not statistically proven.

PMID- 9596327
TI  - Lung mass and large complex liver lesions.

PMID- 9596328
TI  - A middle-aged woman with chronic productive cough diagnosed using sputum wet
      mount examination.

PMID- 9596329
TI  - Cardiomyopathic lentiginosis/LEOPARD syndrome presenting as sudden cardiac
      arrest.
AB  - A 26-year-old apparently healthy man with numerous pigmented skin lesions
      collapsed during an evening party and was resuscitated from ventricular
      fibrillation. Hypertrophic cardiomyopathy and subaortic tunnel were disclosed by
      angiocardiography. A diagnosis of cardiomyopathic lentiginosis/lentigines
      (multiple), electrocardiographic abnormalities, ocular hypertelorism, pulmonary
      stenosis, abnormalities of the genitalia, retardation of growth, and deafness
      (sensorineural) syndrome was made. The patient then underwent treatment with an
      implantable pacer-cardioverter-defibrillator device. Further evaluation revealed
      several well-established features of the disorder. This is the first reported
      case of survival from ventricular fibrillation associated with this rare and
      little known multifaceted syndrome. Disseminated lentiginosis must prompt
      clinicians to evaluate such cases further since underlying disorders may be
      associated with considerable morbidity and, apparently, sudden death.

PMID- 9596330
TI  - Coronary artery spasm complicating anaphylaxis secondary to skin disinfectant.
AB  - We report a patient in whom presumed vasospasm of an angiographically normal
      coronary artery led to severe transmural myocardial ischemia. To our knowledge,
      this is the first case in which an allergic reaction to locally applied
      chlorhexidine caused such a severe reaction.

PMID- 9596332
TI  - Online journals: moving in the right direction.

PMID- 9596331
TI  - False elevation of serum creatinine following skin absorption of nitromethane
      complicates the clinical diagnosis of rhabdomyolysis.
AB  - A patient had extensive blunt trauma from a high-speed crash in which
      nitromethane fuel erupted from the fuel tank and soaked into his protective
      multilayer jumpsuit. The clinical diagnosis was complicated because the
      absorption of nitromethane fuel through the skin and by inhalation falsely
      increased the serum creatinine value when a modified Jaffe reaction was used in
      the laboratory. This spurious value was "unmasked" by the use of an enzymatic
      method to measure the serum creatinine level. A high serum creatinine value
      disproportionate to the level of BUN and recent skin exposure to nitromethane
      were the clinical indications that suggested the differentiation of massive
      rhabdomyolysis from spurious hypercreatinemia. This spurious value was a
      confounding factor in the diagnosis of crush syndrome and rhabdomyolysis.

PMID- 9596333
TI  - Treatment of spontaneous pneumothorax: the clinician's perspective on
      pneumothorax management.

PMID- 9596334
TI  - ACE inhibitor and swallowing reflex.

PMID- 9596335
TI  - Usefulness of carcinoembryonic antigen in pleural effusion diagnosis.

PMID- 9596336
TI  - Pleural fluid pH determination.

PMID- 9596337
TI  - How often should beta-agonists be administered?

PMID- 9596338
TI  - Adrenomedullin: a player at high altitude?

PMID- 9596339
TI  - Solitary pulmonary lesion evaluations.

PMID- 9596340
TI  - A sedation protocol to prevent self-extubation.

PMID- 9596342
TI  - Chemical and electrical stimulation induce rhythmic motor activity in an in vitro
      preparation of the spinal cord from adult turtles.
AB  - Bath application of N-Methyl-D-aspartate (NMDA) and serotonin induced rhythmic
      activity in hindlimb motoneurons in an isolated spinal cord preparation from
      adult turtles. Subthreshold concentrations of NMDA and serotonin accompanied by
      stimulation of the dorsal funiculus also induced rhythmic activity. The induced
      activity in motoneurons and ventral roots displayed characteristics which
      resemble that of locomotion. This activity could be evoked in as few as three
      segments (D8-D10) of the lumbar enlargement isolated from the rest of the spinal
      cord. The existence of intrinsic oscillations in single neurons was revealed in
      the presence of tetrodotoxin. Our findings introduce a new in vitro preparation
      in which electrophysiological and pharmacological tools can be used with ease to
      study mechanisms of central pattern generation in a mature spinal motor network.

PMID- 9596341
TI  - Impairment of dentato-thalamo-cortical pathway in autistic men: language
      activation data from positron emission tomography.
AB  - Recent evidence suggests disturbances of serotonin synthesis affecting the
      dentato-thalamo-cortical pathway in autistic boys. We studied possible effects of
      such disturbances on brain activations for language in autistic adults. Four
      autistic and five normal men were studied while listening to, repeating, and
      generating sentences, using [15(O)]-water positron emission tomography (PET).
      Activation in the right dentate nucleus and in the left frontal area 46 was
      reduced during verbal auditory and expressive language and enhanced during motor
      speech functions in the autism as compared to the control group. The thalamus
      showed group differences concordant with area 46 for expressive language. The
      results may indicate atypical functional specialization of the dentato-thalamo
      cortical pathway and are compatible with a model of region-specific biochemical
      disturbances in the developing autistic brain.

PMID- 9596343
TI  - Endonucleolytic DNA fragmentation is not required for apoptosis of cultured rat
      cerebellar granule neurons.
AB  - Depolarizing concentrations of potassium (K+) promote maturation and survival of
      cerebellar granule neurons in vitro. Withdrawal of potassium from differentiated
      neurons induces morphological and biochemical features of apoptosis, including
      membrane blebbing, nuclear condensation, activation of caspases, and
      internucleosomal DNA fragmentation. Significant DNA fragmentation is detectable
      at 6 h after K+ withdrawal and slowly increases thereafter. Two observations
      indicate that endonucleolytic DNA degradation is neither required nor sufficient
      for K+ withdrawal-induced apoptosis in cerebellar granule neurons: (i) neurons
      are rescued from apoptosis by readdition of K+ up to 8 h after K+ withdrawal,
      when DNA fragmentation has already occurred. (ii) The endonuclease inhibitor,
      aurintricarboxylic acid, inhibits DNA fragmentation as assessed by quantitative
      DNA fluorometry, TUNEL staining, and DNA gel electrophoresis, but not cell death
      or chromatin condensation induced by K+ withdrawal.

PMID- 9596344
TI  - Differential release of cholecystokinin by morphine in rat spinal cord.
AB  - The analgesic efficacy of opioids is reduced in neuropathic pain states and
      increased in inflammation. Since the neuropeptide cholecystokinin (CCK) plays a
      role in the modulation of opiate-induced analgesia, the morphine-mediated release
      of CCK in the spinal cord of rats was compared with in vivo microdialysis in
      normals and different pain models. The effect of systemic and intrathecal (i.t.)
      morphine on the extracellular level of CCK was analyzed in the spinal cord dorsal
      horn of halothane-anaesthetized normal rats as well as during peripheral
      neuropathy and inflammation. No difference was found in basal CCK level among
      groups. However, morphine significantly increased extracellular CCK concentration
      after both systemic and spinal application in intact as well as axotomized rats
      and this effect was naloxone-reversible in non-lesioned animals. Similar results
      were seen in axotomized rats. In contrast, morphine did not induce CCK release
      during carrageenan-induced inflammation. These data provide evidence that the
      ability of opiates to release CCK under different pain states may play a key role
      in their analgesic efficacy.

PMID- 9596345
TI  - Alpha-tocopherol prevents ethanol-induced elevation of [Ca2+]i in cultured canine
      cerebral vascular smooth muscle cells.
AB  - Exposure of cultured canine cerebral vascular smooth muscle cells to ethanol (10
      400 mM) for 1-5 days results in concentration-dependent elevation in resting
      intracellular free calcium ([Ca2+]i) levels. Preincubation of these cultured
      vascular cells with alpha-tocopherol (20 microM), alone, did not produce any
      apparent changes from control resting levels of [Ca2+]i. However, after
      concomitant addition of alpha-tocopherol (20 microM) and ethanol (10-400 mM), the
      rises of [Ca2+]i induced by ethanol were attenuated markedly. These results
      suggest that alcohol-induced lipid peroxidation of cerebral vascular muscle cell
      membranes triggers membrane entry of extracellular Ca2+, which could play an
      important role in ethanol-induced cerebrovasospasm, brain ischemia and stroke.
      Moreover, these new results support the concept recently advanced to suggest that
      alpha-tocopherol-induced amelioration of membrane lipid alterations of cerebral
      vascular cells can prevent ethanol-induced excessive accumulation of [Ca2+]i.

PMID- 9596346
TI  - Amount of sympathetic sprouting in the dorsal root ganglia is not correlated to
      the level of sympathetic dependence of neuropathic pain in a rat model.
AB  - Incomplete peripheral nerve injury often leads to neuropathic pains, some of
      which are relieved by sympathectomy, and results in sympathetic postganglionic
      nerve fiber sprouting in the dorsal root ganglion (DRG). This study was performed
      to see whether the sprouting in the DRG plays a key role in the sympathetic
      dependence of neuropathic pain. To this aim, we compared two groups of rats, both
      of which were subjected to unilateral transection of the inferior and superior
      caudal trunks at the levels between the S1 and S2, S2 and S3, and S3 and S4
      spinal nerves, with respect to sympathetic fiber sprouting; one group showed
      neuropathic pain behaviours (i.e. mechanical and cold allodynia signs) which were
      very sensitive to phentolamine, alpha adrenergic blocker, and the other group
      exhibited no sensitivity. Immuno-histochemical staining with tyrosine hydroxylase
      antibody of the S1-S3 DRGs was not correlated with the sensitivity to
      phentolamine. These results suggest that the degree of sympathetic dependence of
      neuropathic pain is not a function of the extent of the sympathetic
      postganglionic nerve fiber sprouting in the DRG.

PMID- 9596347
TI  - Sleep modifications during cool acclimation in human neonates.
AB  - The present study aimed at testing in human neonates whether the thermal
      acclimation could reduce the sleep disturbances induced by brief cool exposure.
      Six neonates were exposed in incubator to a standardised cool thermal load of 75
      h duration. The results show an increase of the metabolic heat production (VO2:
      +25% reaching 5.68 ml/min per kg) during cool acclimation which is not associated
      with a reduction of the sleep modifications observed on the first cool exposure:
      the increase of active sleep (+15%, +2 min) and the decrease of quiet sleep (
      15%, -11 min) persist and wakefulness after sleep onset increases (+12%, +10
      min). In conclusion, there is no sleep adaptation as cool acclimation progressed.

PMID- 9596348
TI  - Direction-specific impairment of motion perception and spatial orientation in
      downbeat and upbeat nystagmus in humans.
AB  - Downbeat and upbeat nystagmus can be classified as central vestibular syndromes
      in the vertical (pitch) plane of the vestibulo-ocular reflex (VOR) which are
      defined by ocular motor, perceptual, and postural manifestations. While the
      ocular motor syndrome was often studied investigations on the perceptual
      consequences for spatial orientation and motion perception are rare. Subjective
      visual straight ahead (SVA) and perception of object motion were measured in 11
      patients with downbeat (n=6) and upbeat (n=5) nystagmus. Upward deviations of SVA
      (median +5.2 degrees) were found in downbeat nystagmus, and downward deviations
      (median -7.8 degrees) in upbeat nystagmus. SVA was deviated toward the slow phase
      of the vertical nystagmus in the pitch plane and associated with increased fore
      aft body sway. Perception of object motion was more severely impaired for
      vertical (particularly for motion in the direction of slow nystagmus phases) than
      for horizontal directions in both downbeat and upbeat nystagmus. Impairment of
      motion perception in the vertical pitch plane of the VOR is beneficial to the
      extent that it alleviates disturbing oscillopsia due to the involuntary retinal
      slip. Thus, our findings confirm the hypothesis that downbeat and upbeat
      nystagmus reflect a central tone imbalance of the VOR in the vertical pitch plane
      with ocular motor, postural, and perceptual manifestations.

PMID- 9596349
TI  - Function-specific distribution patterns of axon terminals of input neurons in the
      calyces of the mushroom body of the cockroach, Periplaneta americana.
AB  - Input neurons (INs) in the calyces of the mushroom bodies (MBs) of the cockroach
      brain were examined by single- or multiple-staining with cobalt lysine and by
      Golgi impregnation. Olfactory INs had axon terminals with tuft-like, button-like
      or spiny-blebbed arbors in specific concentric zones in calycal neuropil. INs
      which responded to light stimulation had thick brush-like arbors along with
      axonal branches extending radially along the inner layer of calycal neuropil.
      Some of multiglomerular INs and two types of protocerebral INs extended blebbed
      axonal branches to the outer surface layer of calycal neuropil or thick bush-like
      axonal branches with many varicosities to entire calycal neuropil. The
      distribution patterns of dendrites and axon terminals of INs in the calyces
      suggest the existence of functional subdivisions in calycal neuropil.

PMID- 9596350
TI  - Body response to binaural monopolar galvanic vestibular stimulation in humans.
AB  - We investigated the possibility of obtaining an anteroposterior body response to
      galvanic vestibular stimulation (GVS) by applying an equivalent stimulus to both
      sides of the vestibular apparatus. An original 'double fronto-mastoidal'
      stimulation was used on eight subjects standing with their head facing forwards.
      Both the onset and the cut-off of the current did induce an anteroposterior body
      tilt, without any lateral component. The amplitude of the tilt increased as a
      function of stimulus intensity. GVS evokes anteroposterior or lateral sway of
      similar spatio-temporal features according to the stimulation configuration. We
      suggest that the central nervous system makes use of the discrepancy between the
      left and right vestibular activity to orientate the response: equivalent afferent
      flows would result in an anteroposterior body response whereas lateral sway is
      obtained with discrepant ones.

PMID- 9596351
TI  - Phenylethanolamine-N-methyltransferase - immunoreactive nerve terminals afferent
      to the mouse substantia nigra.
AB  - In the substantia nigra pars compacta, many phenylethanolamine-N
      methyltransferase immunoreactive (PNMT-ir) terminals as well as serotonin-ir
      terminals were observed for the first time to be very closely situated to the
      tyrosine hydroxylase (TH)-ir, aromatic L-amino acid decarboxylase-ir, and GTP
      cyclohydrolase I (GCH)-ir dopaminergic cells [Nagatsu, I., Arai, R., Sakai, M.,
      Yamawaki, Y., Takeuchi, T., Karasawa, N. and Nagatsu, T., Neurosci. Lett., 224
      (1997) 185-188]. Immunohistochemical colocalization of TH with GCH or PNMT in the
      somata and dendrites of TH-positive neurons in the rostral ventrolateral
      reticular formation of the medulla oblongata (C1 region, [Hokfelt, T., Fuxe, K.,
      Goldstein, M. and Johansson, O., Brain Res., 66 (1974) 235-251]) was proved by a
      double-labeling immunofluorescence method with a confocal laser-scanning
      microscope, indicating that the neurons are adrenergic. These results suggest
      that dopaminergic neurons in the substantia nigra receive PNMT-ir, adrenergic
      afferents from the C1 region of the medulla oblongata.

PMID- 9596352
TI  - Cyclin-dependent kinase-5 is associated with lipofuscin in motor neurones in
      amyotrophic lateral sclerosis.
AB  - We have studied the distribution of cyclin dependent kinase-5 (cdk-5) within
      spinal cord in sporadic and two superoxide dismutase type 1 (SOD1) familial cases
      of amyotrophic lateral sclerosis (ALS). Although most neurofilament accumulations
      in ALS motor neurones did not appear to contain high levels of cdk-5, intense cdk
      5 immunoreactivity was observed in perikarya of degenerating neurones in many ALS
      cases. Here, cdk-5 co-localised with lipofuscin. Co-localisation of cdk-5 with
      lipofuscin was also observed in some aged non-affected controls although this
      labelling was less intense than the ALS cases. The biogenesis of lipofuscin is
      believed to be linked to oxidative stress and oxidative stress and free radical
      damage have been suggested to be part of the pathogenic process of ALS, possibly
      involving apoptotic mechanisms. cdk-5 has recently been associated with
      apoptosis. These observations suggest a role for cdk-5 in the pathogenesis of
      ALS.

PMID- 9596353
TI  - Detection of a gliotoxic activity in the cerebrospinal fluid from multiple
      sclerosis patients.
AB  - We recently showed that peripheral blood cell supernatants from multiple
      sclerosis (MS) patients, containing reverse transcriptase activity and retroviral
      RNA from the newly human identified multiple sclerosis retrovirus (MSRV), also
      secrete a cytotoxin which induces death of primary mouse cortical glial cells. We
      have hypothesized that macrophages could release this cytotoxin in the
      cerebrospinal fluid. The cerebrospinal fluid cytotoxicity from 166 patients with
      various neurological diseases (including MS patients) was tested on glial cells
      in vitro. Our bioassay shows that a glial cytotoxic activity is significantly
      present in cerebrospinal fluid from patients with relapsing-remitting MS at
      relapse. Since this cytotoxic activity seems to correlate with active cases of
      MS, it may represent a critical pathogenic factor in the neuropathology of MS.

PMID- 9596354
TI  - Effect of the subchronic treatment with the acetylcholinesterase inhibitor
      heptastigmine on central cholinergic transmission and memory impairment in aged
      rats.
AB  - The effect of subchronic administration of the acetylcholinesterase (AChE)
      inhibitor heptastigmine (HEP 0.6 mg/kg s.c. daily for 15 days) was investigated
      on cortical extracellular acetylcholine (ACh) levels and on memory function in
      aged male rats (26 months old at the beginning of the experiments) using
      microdialysis and behavioural techniques. Twenty-four hours after the last
      treatment, cortical ACh levels were significantly higher in rats subchronically
      treated with HEP than in rats treated with saline and AChE activity was still
      inhibited in cortex, hippocampus and striatum. The injection of a challenge dose
      of HEP (0.6 mg/kg s.c.) 24 h after the last treatment produced a faster and a
      more sustained increase of ACh in the cortex of subchronically treated rats
      compared to those repeatedly injected with saline. However, the maximum increase
      of ACh levels after injection of the challenge was comparable in both groups. In
      an object recognition test in which the pretest and test phase were spaced by 45
      days, HEP prevented the deterioration of spatial memory occurring during this
      period, but had no effect on non-spatial memory. The present results suggest that
      moderate inhibition of brain AChE is able to maintain high levels of cortical
      extracellular ACh in aged rats and that this increase matches facilitatory effect
      of HEP on spatial memory.

PMID- 9596355
TI  - Vascular head pain selectively activates ventrolateral periaqueductal gray in the
      cat.
AB  - Electrical stimulation of the superior sagittal sinus is an experimental model of
      migraine which activates neurons within the upper cervical spinal cord. The
      ventrolateral periaqueductal gray has been proposed as an integrative centre for
      the autonomic and behavioural responses to deep pain and also receives
      significant inputs from the upper cervical spinal cord. The noxious-stimulation
      evoked expression of the immediate-early gene c-fos, was used to determine if
      sagittal sinus stimulation activates neurons of the ventrolateral periaqueductal
      gray. The superior sagittal sinus was stimulated in anesthetised cats and Fos
      protein was detected in coronal brain sections using standard avidin-biotin
      immunohistochemistry. A pattern of Fos-positive cells restricted to the caudal
      ventrolateral periaqueductal gray was revealed suggesting that this region may
      mediate the pattern of somatic and autonomic responses characteristic of
      migraine.

PMID- 9596356
TI  - The biomechanics of soccer: a review.
AB  - This review considers the biomechanical factors that are relevant to success in
      the game of soccer. Three broad areas are covered: (1) the technical performance
      of soccer skills; (2) the equipment used in playing the game; and (3) the
      causative mechanisms of specific soccer injuries. Kicking is the most widely
      studied soccer skill. Although there are many types of kick, the variant most
      widely reported in the literature is the maximum velocity instep kick of a
      stationary ball. In contrast, several other skills, such as throwing-in and
      goalkeeping, have received little attention; some, for example passing and
      trapping the ball, tackling, falling behaviour, jumping, running, sprinting,
      starting, stopping and changing direction, have not been the subject of any
      detailed biomechanical investigation. The items of equipment reviewed are boots,
      the ball, artificial and natural turf surfaces and shin guards. Little of the
      research conducted by equipment manufacturers is in the public domain; this part
      of the review therefore concentrates on the mechanical responses of equipment,
      player-equipment interaction, and the effects of equipment on player performance
      and protection. Although the equipment has mechanical characteristics that can be
      reasonably well quantified, the player-equipment interaction is more difficult to
      establish; this makes its efficacy for performance or protection difficult to
      predict. Some soccer injuries may be attributable to the equipment used. The
      soccer boot has a poor protective capability, but careful design can have a minor
      influence on reducing the severity of ankle inversion injuries. Performance
      requirements limit the scope for reducing these injuries; alternative methods for
      providing ankle stability are necessary. Artificial surfaces result in injury
      profiles different from those on natural turf pitches. There is a tendency for
      fewer serious injuries, but more minor injuries, on artificial turf than on
      natural turf pitches. Players adapt to surface types over a period of several
      games. Therefore, changing from one surface to another is a major aetiological
      factor in surface-related injuries. Heading the ball could lead to long-term
      brain damage. Simulation studies suggest the importance of ball mass, ball speed
      and player mass in affecting the severity of impact. Careful instruction and
      skill development, together with the correct equipment, is necessary for young
      players. Most applications of biomechanical techniques to soccer have been
      descriptive experimental studies. Biomechanical modelling techniques have helped
      in the understanding of the underlying mechanisms of performance, although their
      use has been limited. It is concluded that there are still many features of the
      game of soccer that are amenable to biomechanical treatment, and many
      opportunities for biomechanists to make a contribution to the science of soccer.

PMID- 9596357
TI  - Preparatory heart rate patterns in competitive rifle shooting.
AB  - In this study, we examined the relationship between preparatory heart rate
      patterns and competitive shooting performance. Cardiac activity was recorded from
      six elite and six non-elite male rifle shooters during the 6 s before the trigger
      pull. The assessment of shooting performance was based on three variables:
      shooting score, rifle stability and electromyographic (EMG) activity in the upper
      body. Each shooter showed a decrease in the pre-trigger heart rate that did not
      covary with the shooting scores. The magnitude of this change was greater for the
      non-elite shooters compared to the elite shooters, suggesting that the heart rate
      patterns reflected skill-related aspects of preparatory performance. The analyses
      of rifle-hold performance (rifle stability and EMG) suggested that the observed
      heart rate changes were associated with a shooter's attempts to achieve a rigid
      rifle position, but depend on his skill level. Interpretation of preparatory
      heart rate patterns in competitive rifle shooting should not be based solely on
      the attentional focusing aspect, but should also take into account the effects of
      a shooter's psychomotor regulation.

PMID- 9596358
TI  - Physiological profiles of male and female taekwon-do (ITF) black belts.
AB  - Baseline physiological and kinanthropometric data were collected for 11 male and
      12 female elite taekwon-do athletes from the Czech national team for evaluation
      of anthropometry, aerobic and anaerobic capacities, strength, visual reaction
      time, pulmonary function, flexibility and explosive power of the lower limbs
      (vertical jump). Both male and female taekwon-do black belts demonstrated low
      adiposity (8.2 and 15.4% fat, BMI 21.9 and 22.0 kg m(-2), respectively), normal
      reactivity and pulmonary function, above average muscular strength, PWC-170 (3.4
      vs 2.7 W kg(-1)) and aerobic power (54 vs 42 ml min(-1) kg(-1)), and a high
      flexibility (37 and 38 cm) and anaerobic performance (peak power output from a 30
      s Wingate test=14.7 and 10.1 W kg(-1); anaerobic capacity=334 and 242 J kg(-1),
      in males and females, respectively). In male athletes, competitive performance
      was significantly related to maximum power output and upper limb reaction time
      only, whereas in females, performance was related to maximum power output and
      ventilatory threshold level. These variables accounted for 66 and 67% of the
      performance rank in males and females, respectively. Time-motion analysis of
      competition taekwon-do fighting (two times 2 min) revealed 3-5 s bouts of maximum
      exercise alternating with low-intensity periods. This elicits high heart rates
      (100% HRmax) and lactate responses (11.4 mmol l(-1) = 81% LAmax), which agrees
      well with the physiological characteristics of taekwon-do black belts measured in
      laboratory exercise tests.

PMID- 9596359
TI  - The relationship between blood lactate and heart rate responses to swim bench
      exercise and women's competitive water polo.
AB  - The aim of this study was to explore the relationship between physiological
      responses to dry-land testing and to water polo playing. Eight female water polo
      players (mean+/-s: age 26.7+/-5.7 years, height 169+/-6 cm, body mass 65.3+/-7.0
      kg) participated in two assessments. The first involved a discontinuous
      incremental arm test to exhaustion on an isokinetic swim bench. Blood lactate was
      determined from finger-prick blood samples and heart rate was recorded at
      increasing exercise intensities. The highest (peak) values for blood lactate
      (5.1+/-0.2 mmol l(-1)), exercise intensity (79+/-5.2 W) and heart rate (146+/-6
      beats min(-1)) were recorded at exhaustion. Also, the exercise intensity and
      heart rate at a blood lactate concentration of 4 mmol l(-1) were established. The
      second assessment involved determination of blood lactate and heart rate
      immediately after each quarter of a different water polo game for each subject.
      The mean (+/-s(x)) blood lactate and heart rate for each quarter of the game were
      as follows: 3.5+/-0.4, 4.3+/-0.5, 4.3+/-0.7 and 4.6+/-0.5 mmol l(-1); 138+/-10,
      149+/-12, 151+/-9 and 154+/-8 beats min(-1), respectively. None of the peak
      values on the swim bench correlated with blood lactate or heart rate responses to
      game-playing. However, the mean exercise intensity at 4 mmol l(-1) lactate (64+/
      5 W) correlated with the fourth quarter values of both blood lactate
      concentration (r=-0.82, P=0.01) and heart rate (r=-0.93, P< 0.001). These results
      show that submaximal metabolic responses to exercise on a swim bench are closely
      correlated with metabolic responses to water polo game-playing.

PMID- 9596360
TI  - Modelling the relationship between isokinetic muscle strength and sprint running
      performance.
AB  - Muscle strength is thought to be a major factor in athletic success. However, the
      relationship between muscle strength and sprint performance has received little
      attention. The aim of this study was to examine the relationship in elite
      performers of isokinetic muscle strength across three lower limb joints and
      sprinting performance, including the use of theoretical models. Eight rugby
      players, eight track sprinters and eight competitive sportsmen, all elite
      national or regional competitors, performed sprints over 15 m and 35 m with times
      recorded over 0-15 m and 30-35 m. Isokinetic torque was measured at the knee, hip
      and ankle joints at low (1.05 rad s(-1)), intermediate (2.09 or 2.62 rad s(-1))
      and high (3.14 or 4.19 rad s(-1)) speeds during concentric and eccentric muscle
      actions. Using linear regression and expressing sprint performance as time, the
      strongest relationship, for the joint actions and speeds tested, was between
      concentric knee extension at 4.19 rad s(-1) and sprint performance (0-15 m times:
      r=-0.518, P< 0.01; 30-35 m times: r=-0.688, P< 0.01). These relationships were
      improved for 0-15 m, but not for 30-35 m, by expressing torque relative to body
      mass (0-15 m times: r=-0.581; 30-35 m times: r=-0.659). When 0-15 m performance
      was expressed as acceleration rather than time, the correlation was improved
      slightly (r=0.590). However, when the data (0-15 m times) were fitted to the
      allometric force model proposed by Gunther, 77% of the variance in concentric
      knee extension torque at 4.19 rad s(-1) could be explained by 0-15 m times, limb
      length (knee to buttocks) and body mass. The fitted parameters were similar to
      those from the theoretical model. These findings suggest that the relationship
      between isokinetic muscle strength and sprint performance over 0-15 m (during the
      acceleration phase) is improved by taking limb length and body mass into account.

PMID- 9596361
TI  - A comparison of voluntary versus stimulated strength training of the human
      adductor pollicis muscle.
AB  - The effects of voluntary versus electrically stimulated isometric strength
      training of the adductor pollicis on muscle strength were compared. The adductor
      pollicis of one hand was trained using voluntary contractions at 50% of the
      maximum voluntary contraction force, and the other with 30 Hz tetani (stimulated
      contractions), which produced a force equivalent to 30-50% of the maximum
      voluntary force. Tetani were delivered with surface electrodes placed over the
      ulnar nerve at the wrist. Both protocols resulted in large, significant increases
      in maximum voluntary strength of 79+/-44% (voluntary) and 74+/-41% (stimulated)
      (mean+/-s; P< 0.002). The time course of the changes was very similar for both
      protocols and there was no significant difference between the strength increases
      produced by the two protocols. The large gains resulting from stimulated training
      argues against central adaptations as a major contributor to the strength
      increases following training.

PMID- 9596362
TI  - The effects of oral creatine supplementation on performance in single and
      repeated sprint swimming.
AB  - We studied the effects of oral creatine supplementation on sprint swimming
      performance in 14 elite competitive male swimmers. The subjects performed a
      single sprint (1 x 50 yards [45.72 m]) and repeated sprint set (8 x 50 yards at
      intervals of 1 min 30 s) before and after a 5 day period of either creatine (9 g
      creatine + 4.5 g maltodextrin + 4.5 g glucose day(-1)) or placebo (18 g glucose
      day(-1); double-blind protocol) supplementation. Venous and capillary blood
      samples were taken for the determination of plasma ammonia, blood pH and lactate.
      Mean times recorded for the single 50 yard sprint were unchanged as a result of
      supplementation (creatine vs control, N.S.). During the repeated sprint test,
      mean times increased (P< 0.01, main effect time) during all trials, but
      performance was improved as a result of creatine supplementation (sprints 1-8:
      control pre-, 23.35+/-0.68 to 26.32+/-1.34 s; control post-, 23.59+/-0.66 to
      26.19+/-1.48 s; creatine pre-, 23.20+/-0.67 to 26.85+/-0.42 s; creatine post-,
      23.39+/-0.54 to 25.73+/-0.26 s; P < 0.03, group x trial interaction). Thus the
      percentage decline in performance times was reduced after creatine
      supplementation (control, 12.7+/-5.7% vs 11.0+/-5.5%; creatine, 15.7+/-4.3% vs
      10.0+/-2.5%; P< 0.05, group x trial interaction). The metabolic response was
      similar before and after supplementation, with no differences in the blood
      lactate or pH response. Plasma ammonia was lower on the second trial (P< 0.05,
      main effect trial), but this could not be attributed to the effect of
      supplementation (group x trial interaction, N.S.). A further urinary analysis
      study supported these findings by demonstrating an approximately 67%
      (approximately 26 g) retention of the administered creatine in this group of
      swimmers after an identical supplementation regimen. In summary, our results
      suggest that ingesting 9 g creatine per day for 5 days can improve swimming
      performance in elite competitors during repeated sprints, but appears to have no
      effect on a single 50 yard sprint.

PMID- 9596364
TI  - The immediate effects of local trauma on the shape of the cricoid cartilage.
AB  - Injury-induced abnormal development of the cricoid ring has been demonstrated in
      previous growth studies. In this study we focused on the immediate effects of
      various types of lesions to the cricoid, eliminating the influence of inserting
      muscles. In isolated, vital cricoids (cricoid explants) the anterior arch was
      split, creating a small gap between the cut ends. Previous injury to the internal
      surface of the cricoid ring resulted in a three to four fold increase of the
      diameter of the gap, actually widening the interrupted cricoid. On the contrary,
      injuring the external surface of the cricoid cartilage prior to anterior cricoid
      split, leads to an overlap of the cut edges, and a narrowing of the ring. These
      injury-specific changes in shape of the cricoid ring are ascribed to the release
      of interlocked stresses, present in the cartilage. It is suggested that the
      demonstrated methods to change the shape of the cricoid ring in a predictable
      way, are relevant for the treatment of patients with cricoid malformation.

PMID- 9596363
TI  - Inhibition of the quadriceps muscles in elite male volleyball players.
AB  - Inhibition of the quadriceps muscles was assessed in 13 elite male volleyball
      players using the interpolated twitch technique. This technique involves applying
      an electrical stimulus to the voluntarily contracted quadriceps muscles to
      estimate the number of motor units not fully activated during the contraction.
      Knee extensor moments and muscle inhibition were measured during isometric
      contractions at knee angles of 30 degrees and 60 degrees from full extension. A
      medical history of knee joint injury and pain experienced in the knee during
      testing were assessed. Previous knee joint injury did not affect the knee
      extensor moments, but produced a difference in muscle inhibition: muscle
      inhibition in legs with previous injuries was significantly lower than muscle
      inhibition in legs with no previous injury. Moderate pain in the knee during
      testing did not affect muscle inhibition, but was associated with reduced knee
      extensor moments. We consider that the loss in knee extensor moments associated
      with pain might be caused by atrophy of the quadriceps muscles as a consequence
      of the disrupted training routine. The lower muscle inhibition in volleyball
      players with previous injury suggested that the intense rehabilitation programme
      that these athletes undergo after knee injury improves muscle activation. As a
      result, athletes with previous knee joint injuries were able to produce the same
      knee extensor moments as athletes with no previous injury, probably because of
      their ability to recruit the available motor units more completely. This
      recruitment may compensate for the possible loss in muscle mass encountered
      during the period of injury and detraining.

PMID- 9596365
TI  - Gastroesophageal reflux association with laryngomalacia: a prospective study.
AB  - OBJECTIVE: To identify the incidence and clinical role of gastroesophageal reflux
      (GER) in patients with laryngomalacia. DESIGN: Prospective evaluation of
      consecutive infants with a new diagnosis of laryngomalacia with an initial
      questionnaire, a barium esophagram or 24 h pH probe and record of their
      subsequent clinical course. SETTING: A large, tertiary pediatric referral center
      and its associated outpatient clinic. PATIENTS: New diagnosis of laryngomalacia
      in 33 consecutive infants were evaluated by questionnaire and 27 of these were
      evaluated for GER. RESULTS: GER was observed in 64% of patients and was
      significantly associated with severe symptoms and complicated clinical course (P
      = 0.0163). The presence of smokers in the infant's household negatively impacted
      his or her clinical course and symptomatology (P = 0.013) as did the presence of
      other major, concurrent medical problems (P = 0.065). CONCLUSIONS: In patients
      with laryngomalacia, GER was significantly associated with severe symptoms (a
      complicated clinical course), as was smoking in an infant's household and other
      significant medical problems.

PMID- 9596366
TI  - Evaluation of balance disturbances in children with middle ear effusion.
AB  - OBJECTIVES: Vertigo and dizziness are not common complaints in childhood, but are
      present more often than formerly thought. These symptoms are usually caused by
      otitis media (OM) and middle ear effusion (MEE), two of the most common disorders
      in children, but were not studied until recently. The purpose of this study was
      to determine objectively the incidence of balance-related symptoms occurring in
      children with long lasting MEE and to determine if these symptoms resolve
      following the insertion of ventilation tubes (VT). METHODS: In total 64 children,
      aged between 4.5 and 7.5 years, were studied using the Bruininks-Oseretsky tests
      for motor proficiency, before and after insertion of VT. They were compared to 57
      healthy children with no history of middle ear diseases. RESULTS: Pathological
      findings were identified in 39 children with chronic MEE, as compared to only
      four children of the controls. Following VT insertion the symptoms and signs of
      balance disturbances resolved in mostly all the operated children. CONCLUSIONS:
      The results of this study indicate that balance-related symptoms often
      encountered in young children may result from chronic MEE and that these symptoms
      resolve following ventilation of the middle ear.

PMID- 9596367
TI  - Foreign bodies of the hard palate.
AB  - Foreign bodies of the hard palate are rare occurrences with only 11 reported
      cases in the literature. These patients can present to the Otolaryngologist in a
      variety of ways and often with confusing histories. We present seven cases of
      foreign bodies adherent to the hard palate. The age range was three to eighteen
      months and the most common referring diagnosis was a suspected tumor (five
      patients). The most common object removed was a nut shell. In six of the seven
      cases the foreign body could be removed in the ambulatory clinic without the need
      for sedation or anesthesia. The clinical presentation, incidence and management
      is reported and discussed with reference to the literature.

PMID- 9596368
TI  - Tonsillar lymphocyte subsets in recurrent acute tonsillitis and tonsillar
      hypertrophy.
AB  - Recurrent acute tonsillitis is usually produced directly by micro-organisms,
      mainly beta-hemolytic streptococcus. Idiopathic tonsillar hypertrophy is
      presented without infection history and usually leads to obstructive sleep apnea.
      We have measured lymphocyte subsets in tonsillar cellular suspensions of
      infectious and obstructive tonsillar pathology by flow cytometry. Comparing with
      peripheral blood, the CD4+/CD8+ ratio for tonsillar pathology varies from 4.0 to
      5.0 while in peripheral blood the ratio was 1.3. In tonsils the ratio of B
      lymphocytes/T lymphocytes is 1.6, being 0.3 in peripheral blood, cytotoxic T
      lymphocytes represent 8% in tonsils and 29% in peripheral blood, virgin or
      nonstimulated T lymphocytes (CD4+ CD62L+) consist of 3% in tonsils and 16% in
      peripheral blood. The immature B lymphocytes (CD20+ CD5+) represent 23% in
      tonsils and 12% in peripheral blood. In regards to NK cells (CD3- CD16+), 1% was
      found in tonsils and 11% in peripheral blood. In tonsils B lymphocytes and a low
      proportion of cytotoxic T lymphocytes predominate, in comparison to peripheral
      blood, with a CD4+/CD8+ ratio four times greater than tonsils. We have found in
      tonsils a significant increase of T cells (CD3+ and TCR alpha+ beta+) in
      infectious processes in comparison to obstructive pathology.

PMID- 9596369
TI  - A nation-wide, population-based survey of otitis media and school achievement.
AB  - The purpose of the study was to evaluate whether there is an association between
      early recurrent otitis media and later school achievement. A nation-wide,
      population-based random cluster sampling of 1708 children in 119 school classes
      was performed throughout Finland. Data were collected with questionnaires sent to
      the parents and teachers of the children. Teachers evaluated each child's
      performance at school, and the association between the number of episodes of
      early otitis media and school achievement was determined. Recurrent otitis media
      episodes before the age of 3 years associated significantly with lower
      performance in mathematical skills (risk ratios [RR] 1.2-1.4, 95% confidence
      intervals [95% CI] 1.0-1.7, P-values 0.04-0.02) and classroom concentration (RR
      1.4, 95% CI 1.1-1.8, P-value 0.02) among the girls. The boys with recurrent
      otitis episodes performed more poorly in reading (RR 1.3, 95%, CI 1.0-1.6, P
      value 0.05) and oral performance (RR 1.2, 95% CI 1.1-1.4, P-value 0.01). No
      association between otitis episodes after the age of 3 years and school
      achievement was found. Our findings suggest that recurrent otitis media episodes
      before the age of 3 years have adverse long-term consequences even when treated
      actively. Even though the risk ratios were low our finding is important because
      recurrent otitis media is a common problem during infancy and school achievement
      has many practical influences on a child's future.

PMID- 9596370
TI  - Lipomas of the head and neck in children.
AB  - Head and neck lipomas in the pediatric population are rarely described in the
      literature. Two patients who presented to the Hospital for Sick Children with
      rapidly enlarging head and neck lipomas are presented. Radiographic imaging,
      including CT and MRI, as well as fine needle aspiration implicated a lipoma as
      the probable diagnosis. Both patients were treated by surgical excision. The
      clinical behavior, diagnostic work-up and treatment of these rare lesions are the
      focus of this study.

PMID- 9596371
TI  - Recurrent therapy resistant mastoiditis by Mycobacterium cheilonae abscessus, a
      nontuberculous mycobacterium.
AB  - A rare case of recurrent mastoiditis is described with abscess formation caused
      by a nontuberculous mycobacterium (NTM) Mycobacterium chelonae abscessus. The
      exceptionally slow wound healing after repeated surgical debridement was
      striking. A literature study showed that in contrast with NTM infections of other
      parts of the body, infections of the middle ear were most commonly seen in
      immunocompetent children. If a case of chronic unilateral otitis media shows
      insufficient response to antibiotic therapy and surgical debridement,
      mycobacterial infection should be considered. The case described below
      illustrates the importance of histopathological and microbiological
      investigations.

PMID- 9596372
TI  - Unilateral total loss of auditory and vestibular function as a complication of
      mumps vaccination.
AB  - A case of a young girl manifesting sudden unilateral total loss of auditory and
      vestibular function following administration of a mumps vaccine is reported. This
      is supposed to be caused by adverse reaction of the vaccination.

PMID- 9596373
TI  - Ectopic cervical thymic masses in infants: a case report and review of the
      literature.
AB  - Ectopic cervical thymic tissue is a rare cause of neck masses in infants with
      only nine cases reported in the literature. This entity should be considered in
      the differential diagnosis of infantile neck masses to prevent inadvertent total
      thymectomy and its possible deleterious effects on the developing immune system.
      The case report of a 2-month-old infant with ectopic thymic tissue presenting as
      a solid cervical mass is reviewed as is the literature of such lesions. The
      embryology of the thymus, the effect of early total thymectomy in laboratory
      animals, and the management of neck masses in infants are discussed.

PMID- 9596374
TI  - Extranasopharyngeal angiofibroma in a 15-month-old child.
AB  - Angiofibromas are usually characterized by typical location with involvement of
      the posterior nasal cavity and nasopharynx. They are most commonly found in
      adolescent males. Despite these facts, a case of an angiofibroma presented in a
      15-month-old boy at an atypical site anterior and medial to the lacrimal sac. The
      tumor was resected via an endonasal, micro-endoscopic approach avoiding an
      external incision.

PMID- 9596375
TI  - The feasibility of a syringe-needle-exchange program in Vietnam.
AB  - Since the beginning of the HIV/AIDS epidemic, syringe-exchange programs have been
      established in a number of developed countries and have proven effective in
      reducing the transmission of HIV. Very few similar programs have been established
      in developing countries. This study reports on the feasibility of establishing a
      syringe-exchange program in Vietnam. Process data collected since the beginning
      of the program indicate the feasibility of establishing such a program as well as
      highlight a number of important issues. These issues are: 1) Acceptability of the
      program in the community which has been achieved through workshops with key
      community people including the local police; 2) training and recruitment of ex
      user outreach workers; 3) the distribution of clean syringes and needles through
      outreach services rather than at established exchange sites; 4) the establishment
      of appropriate methods for the collection of used injection equipment. Further
      research is needed to examine the efficacy of the program in reducing risks and
      acceptability of the program in the larger society.

PMID- 9596376
TI  - Harm reduction and street-based program: looking into Nepal.
AB  - In August 1991 the Lifesaving and Lifegiving Society (LALS) became the first
      nongovernmental organization in Nepal to work with injecting drug users (IDUs) to
      reduce the harm caused by drugs in order to prevent HIV/AIDS. Its mission is to
      provide education, counseling, and primary health care, as well as bleach,
      sterile water, condoms, and new needles and syringes to IDUs to lower their risk
      of acquiring blood-borne diseases. An evaluation of the program found that the
      prevalence of HIV infection among IDUs who were in regular contact with the
      program from 1991 to 1994 was 1.6%. No new cases of HIV infection were detected
      among participants in either 1993 or 1994. Though a harm reduction program is
      expensive to implement and sustain in Nepal, through its nonjudgmental,
      noncoercive, and confidential philosophy, LALS has engaged drug users into
      recovery and given them a platform by which they are able to address their
      concerns in a public forum.

PMID- 9596377
TI  - Harm reduction in the hills of northern Thailand.
AB  - The human immunodeficiency virus (HIV) pandemic has swept through injecting drug
      user (IDU) communities around the world. Once HIV is present in an IDU community,
      seroprevalence rates escalate rapidly unless immediate and comprehensive
      prevention methods are put in place. Such measures often include providing IDUs
      with sterile injecting equipment and dispensing methadone or other opiate
      substitution formulas. These measures fall under the rubric of harm reduction-an
      attempt to reduce the harm to drug users, their families, and communities,
      including preventing or limiting the transmission of HIV and other blood-borne
      viruses. In Thailand, HIV-1 spread rapidly among IDUs with seroprevalence rates
      jumping from 1 to 40% in the space of a year. Current incidence rates are
      estimated at 11 per 100 person years. This paper describes the establishment and
      implementation of needle and syringe exchanges among injecting drug users in nine
      Hilltribe communities in Northern Thailand. The exchanges have been operating for
      between 1 and 3 years and have been effective in limiting the transmission of HIV
      within these small communities. The needle and syringe exchanges are run by
      indigenous staff with the cooperation of the community and provide a good example
      of the feasibility of establishing locally-run, community-based harm reduction
      programs.

PMID- 9596378
TI  - Syringe exchange in Germany.
AB  - Syringe exchange in Germany is clearly linked to a recent shift of local
      responses to drug-use(r) associated problem. Since the end of the 1980s,
      metropolitan communities in Northern and Central Germany-concerned by the
      emergence of "Open Drug Scenes," increasing HIV and mortality rates among drug
      users, and drug-use-related property crime-began to favor measures of survival
      oriented drug-user help. While the Federal Government still favors repression and
      law enforcement efforts, they nevertheless made syringe exchange explicitly legal
      in 1992-some 5 years after the creation of local Syringe Exchange Programs. In
      general, the new approach of local authorities includes a variety of services,
      such as housing facilities, crisis intervention centers, primary medical care,
      maintenance with substitute drugs, and syringe exchange programs. The creation of
      pilot heroin maintenance programs is planned for Frankfurt and Hamburg. While the
      established programs are successfully functioning in large cities such as
      Hamburg, Bremen, and Frankfurt, the demand for sterile needles and syringes
      remains unmet in smaller cities and in the conservative governed Bundeslander
      (states), where pharmacies remain the primary and often single legal supply
      source for syringes. Another major problem continues to be the drug-use situation
      in prisons. Although injection drug use is common in prisons, injection equipment
      is not legally available for the 10,000 injecting drug users imprisoned at any
      given time. Two of Germany's 220 prisons started an experimental syringe exchange
      in 1996.

PMID- 9596379
TI  - Injecting equipment provision in Australia: the state of play.
AB  - Injecting equipment provision measures in Australia can be judged reasonably
      successful as HIV prevention measures. In the capital cities of all Australian
      States and Territories, access to needles and syringes is easy, at least during
      the day in at least some areas. In conjunction with peer education and other
      activities, needle and syringe supply appears to have led to a change in norms
      away from the sharing of needles and other injecting equipment among at least
      older heroin injectors in large population centers. However, in many other areas,
      and in many subpopulations-particularly further marginalized groups such as
      Aboriginal and Vietnamese-Australian injectors-messages about HIV/AIDS risk are
      either not penetrating or are being ignored, and needle and other equipment
      sharing still appears to be common. The strategy of providing access to needles
      and syringes as a separate activity from peer education among injecting drug
      users (IDUs) needs to be reconsidered in the light of the widespread epidemic of
      hepatitis C among Australian IDUs. The level of supply of all injecting equipment
      also needs to be increased to assist all IDUs in learning and carrying out an
      aseptic injecting technique given the lack of an effective disinfection technique
      to prevent the spread of hepatitis C, and the problems surrounding both the
      promotion of disinfection and the promotion of noninjecting routes of
      administration.

PMID- 9596380
TI  - Syringe exchange in Canada: good but not enough to stem the HIV tide.
AB  - This article provides a historical perspective on the development of syringe
      exchange in Canada, the Canadian legal and policy context, evaluation and
      monitoring strategies, and current challenges facing HIV prevention efforts among
      injecting drug users. Despite the fact that it is legal to sell, exchange, or
      provide an IDU with a syringe and there are no laws in Canada requiring a
      physician's prescription to justify possession of a syringe, policy development
      and programming have not been adequate to hold HIV at bay in several cities
      across the country. Although there have been concerted efforts by syringe and
      needle exchange programs to increase the supply of injecting equipment, HIV
      prevalence continues to rise, provoking a rethinking of the role of syringe
      exchange. In a coordinated strategy for HIV prevention among drug users in
      Canada, needle and syringe exchange is not itself in question; however,
      ghettoization and needle quota systems may have had an adverse impact on
      prevention programming. A national action plan has been developed which aims to
      decentralize both methadone maintenance and syringe and needle exchange programs,
      increase access to detoxification and treatment modalities, and advocate for
      changes in the criminal justice system and law enforcement practices.

PMID- 9596381
TI  - Syringe exchange as a social movement: a case study of harm reduction in Oakland,
      California.
AB  - The federal ban on funding for syringe exchange programs (SEPs) has greatly
      hampered attempts to prevent the spread of HIV among injection drug users in the
      United States. State laws prohibiting the possession and/or distribution of
      syringes have made SEPs illegal. These factors have lent a unique social movement
      quality to harm reduction efforts in the United States. Using a social movement
      perspective, this paper explores dynamics of the implementation and defense of
      the syringe exchange program in Oakland, California. The advantages and
      disadvantages of the social movement aspects of harm reduction are discussed.

PMID- 9596382
TI  - Evaluating needle exchange: a description of client characteristics, health
      status, program utilization, and HIV risk behavior.
AB  - This study was designed to describe demographic and drug use characteristics,
      health status, and HIV-related risk behavior among clients attending the San
      Francisco needle exchange program (NEP), and to assess the relationship between
      NEP utilization and risk behavior. Randomly selected clients were interviewed
      when they visited the NEP. Participants were of diverse ethnicity, had a mean age
      of 38.2, and 72% were male. Many reported being homeless (25%), unemployed (34%),
      uninsured (52%), and having an episode of infectious disease in the past 2 years
      (36%). Clients who received a higher proportion of their needles from the
      exchange were less likely to report sharing of needles or rinse water. Clients
      who attended the exchange more frequently were more likely to clean their skin
      prior to injecting and less likely to use the same needle repeatedly. Frequency
      of visiting the NEP was not associated with the likelihood of sharing needles or
      rinse water. Efforts to evaluate needle exchange in the United States will
      benefit from descriptive reports from other NEP programs, and the use of
      nonexchange comparison groups.

PMID- 9596383
TI  - Hepatitis C virus transmission dynamics in injection drug users.
AB  - Hepatitis C virus (HCV) presents several challenges to the development of
      prevention programs. HCV infection is persistent in up to 80% of cases, and
      viremic individuals may transmit infection to others. With 65-90% of injection
      drug users anti-HCV positive, a large reservoir of infection exists in most drug
      injector populations. Studying the genetic variability of HCV infections could
      permit researchers to reconstruct chains of viral transmission in IDUs. However,
      the relationship of HCV to HIV epidemiology remains unclear and may depend on
      whether the proportions of infectious persons in the population are similar for
      both viruses.

PMID- 9596384
TI  - From ideology to logistics: the organizational aspects of syringe exchange in a
      period of institutional consolidation.
AB  - The initial period in the establishment of syringe exchange projects is often
      characterized by overt conflict: between community AIDS activists, on the one
      hand, and public officials and political leaders who remain ideologically opposed
      to the introduction of measures perceived as condoning illicit drug use. In this
      context, professionals concerned with legitimating the new institutions of
      syringe exchange may sometimes neglect aspects of their everyday logistics and
      social organization, obscuring the important choices which have to be made to
      carry these initiatives forward. In particular, the contrast between formally
      constituted institutions-the "storefront" or "community-based" syringe exchange
      programs (SEPs)-and the model of low-threshold syringe availability through
      pharmacies, vending machines, and user networks, is here presented not as an
      either/or choice but rather as a pair of complementary strategies which respond
      to diverse needs and target different populations. The advantages and
      disadvantages of each particular approach make it likely that maximum
      effectiveness will be achieved through a combination of every possible form of
      needle distribution, each tailored to specific and cultural circumstances. The
      case is here examined in the light of the experience of the SEPs in New York
      City, from their clandestine origins in 1990 through their first years of
      official functioning in 1992-1996.

PMID- 9596386
TI  - Recovery of arm function in patients with paresis after traumatic brain injury.
AB  - OBJECTIVE: To characterize the frequency of recovery of arm paresis in patients
      with traumatic brain injury (TBI) admitted to rehabilitation. DESIGN:
      Retrospective review identifying a cohort of patients with moderate or severe arm
      paresis after TBI followed at least 6 months postinjury. SETTING: Freestanding
      acute rehabilitation hospital TBI unit. PATIENTS AND METHODS: Forty-four patients
      with moderate to severe arm paresis were selected from 264 consecutive admissions
      and characterized by injury pathology subtype, injury severity (duration of
      unconsciousness [loss of consciousness, LOC] and posttraumatic amnesia [PTA]),
      age, and level of paresis according to Brunnstrom Stages of Recovery (BS 1 to 6).
      Patient groups with and without arm paresis were compared according to these
      variables (t tests and chi(2)). MAIN OUTCOME MEASURES: Recovery of arm paresis to
      isolated motor function (BS 5 or 6) and time to achieve recovery. Recovered and
      nonrecovered patients were compared (Mann-Whitney, t tests, and chi(2)) on injury
      severity, initial level of paresis, age, time to rehabilitation admission, and
      pathology subtype. Time to recovery was compared for patients at different levels
      of initial paresis, ranges of LOC, and pathology subtypes (Mann-Whitney and
      Kruskal-Wallis tests). RESULTS: Forty-four patients (17%) had moderate (BS 3 to
      4) or severe (BS 1 to 2) paresis at rehabilitation admission. They were more
      severely injured than nonparetic patients based on longer LOC (p < .002) and PTA
      (p < .009). Thirty-six patients (82%) recovered by 6 months; 72% of these
      recovered by 2 months. If still paretic at 2 months, only 56% recovered. Mean
      recovery time was 6.9 weeks (SD, 6.1) from injury. Time to recovery was best
      predicted by initial level of paresis and injury severity (r2 = .48), but not
      age. Patients with diffuse injury tended towards a more protracted recovery (7.9
      weeks, SD 6.5) than patients with focal injury (4.2 weeks, SD 3.9) (p = .08) and
      only those with diffuse injury showed further recovery after 3 months.
      CONCLUSIONS: Arm paresis after TBI is relatively infrequent. Most patients
      recover by 2 months but later recovery is possible, especially in patients with
      primarily diffuse brain damage. Recovery is highly related to initial impairment,
      injury severity, and distribution of brain injury.

PMID- 9596385
TI  - Combined exercise and motivation program: effect on the compliance and level of
      disability of patients with chronic low back pain: a randomized controlled trial.
AB  - OBJECTIVE: To assess the effect of a combined exercise and motivation program on
      the compliance and level of disability of patients with chronic and recurrent low
      back pain. DESIGN: A double-blind prospective randomized controlled trial.
      SETTING: Physical therapy outpatient department, tertiary care. PATIENTS: Ninety
      three low back pain patients were randomly assigned to either a standard exercise
      program (n = 49) or a combined exercise and motivation program (n = 44).
      INTERVENTIONS: Patients were prescribed 10 physical therapy sessions and were
      advised to continue exercising after treatment termination. The motivation
      program consisted of five compliance-enhancing interventions. Follow-up
      assessments were performed at 3 1/2 weeks, 4 months, and 12 months. MAIN OUTCOME
      MEASURES: Disability (low back outcome score), pain intensity, physical
      impairment (modified Waddell score, fingertip-to-floor distance, abdominal muscle
      strength), working ability, motivation, and compliance. RESULTS: The patients in
      the motivation group were significantly more likely to attend their exercise
      therapy appointments (p = .0005). Four and 12 months after study entry there was
      a significant difference in favor of the motivation group with regard to the
      disability score (p = .004) and pain intensity (p < or = .026). At 4 months,
      there was a significant advantage for the motivation group in the fingertip-to
      floor distance (p = .01) and in abdominal muscle strength (p = .018). No
      significant differences were found in motivation scores, self-reported compliance
      with long-term exercise, and modified Waddell score. In terms of working ability,
      there was a trend favoring the combined exercise and motivation program.
      CONCLUSION: The combined exercise and motivation program increased the rate of
      attendance at scheduled physical therapy sessions, ie, short-term compliance, and
      reduced disability and pain levels by the 12-month follow-up. However, there was
      no difference between the motivation and control groups with regard to long-term
      exercise compliance.

PMID- 9596387
TI  - Side effects of chronic intrathecal baclofen on erection and ejaculation in
      patients with spinal cord lesions.
AB  - OBJECTIVE: Assess modifications of sexual function in men treated with
      intrathecal baclofen for spinal spasticity. DESIGN: Prospective before-after
      trial. SETTING: A rehabilitation department of a university hospital; follow-up
      was on an outpatient basis. PATIENTS: A convenience sample of nine consecutively
      recruited men with spinal cord injury or multiple sclerosis who were receiving
      intrathecal baclofen by an implantable pump; average follow-up was 44.4 months.
      MAIN OUTCOME MEASURES: A questionnaire focusing on: libido; ability to sustain
      reflexive and psychogenic erections; rigidity, evaluated by a visual analog
      scale; maximum duration of erection; possibility of ejaculation. RESULTS: Libido
      and the ability to obtain psychogenic or reflexogenic erections were not
      modified. However, eight patients reported a decrease of erection rigidity and/or
      duration. Ejaculation was possible in three cases before implantation. It
      disappeared in two patients, and was more difficult to obtain in the last one. It
      reappeared after treatment withdrawal. No differences were found between multiple
      sclerosis and spinal cord injured patients. CONCLUSION: Intrathecal baclofen may
      compromise erection and ejaculation. This effect is reversible. Patients should
      be informed of this effect.

PMID- 9596388
TI  - Functional task benchmarks for stroke rehabilitation.
AB  - OBJECTIVE: To determine typical outcome "benchmarks" for 18 functional tasks in
      patients undergoing stroke rehabilitation. The benchmarks are intended to serve
      as points of reference to which the outcomes of patients with similar impairments
      and degrees of disability can be compared. SUBJECTS: Records from 26,339 stroke
      patients discharged from 252 inpatient facilities across the United States that
      submitted 1992 data to the Uniform Data System for Medical Rehabilitation.
      METHODS: Stroke impairment was detailed as the presence or absence of hemiparesis
      resulting from stroke and the side(s) of involvement. Within each of five stroke
      impairment categories, patients were further classified by the Functional
      Independence Measure-Function-Related Groups (FIM-FRGs) into nine syndromes by
      degree of disability (admission motor and cognitive FIM scores) and by age.
      Outcomes were determined for each stroke syndrome at patients' discharge from
      medical rehabilitation. MAIN OUTCOME MEASURES: Patients' median performance
      levels on each of the 18 items making up the FIM, length of stay, and community
      discharge rates. RESULTS: The majority of patients whose admission motor FIM
      scores were above 37 were able to eat, groom, dress the upper body, and manage
      bladder and bowel functions independently by discharge. In addition to these
      tasks, most of those whose motor FIM scores were above 55 were able to dress the
      lower body, bathe, and transfer onto a chair/bed or toilet. The majority of
      patients whose initial motor FIM scores were above 62 points and whose cognitive
      FIM scores were above 30 gained independence in most tasks, including stair
      climbing and tub transfers. Community discharge rates ranged from 51.6% for the
      group of patients with the most severe disabilities to 99.2% for the group with
      the least severe disabilities. CONCLUSION: The clinician can apply these
      benchmarks to guideline development and quality improvement, and in establishing
      patient goals.

PMID- 9596389
TI  - Applied forces and associated physiologic responses induced by axial spinal
      unloading with the LTX 3000 Lumbar Rehabilitation System.
AB  - OBJECTIVE: To measure forces applied to the body and associated changes in
      physiologic responses during axial spinal unloading (gravity-dependent traction)
      using the LTX 3000 Lumbar Rehabilitation System. DESIGN: Lumbar unloading was
      induced in 17 healthy subjects. The following parameters were measured: (1)
      percentage of total body weight unloaded; (2) forces applied onto and below the
      rib cage and local changes in cutaneous blood flow; (3) alteration of the applied
      forces to the seat strap associated with lumbar lengthening; and (4) changes in
      respiratory rates, respiratory minute volumes, heart rate, and blood pressure.
      RESULTS: The average pressure applied to the rib cage for thoracic immobilization
      without unloading was 73 +/- 26mmHg. Lumbar unloading caused these pressures to
      increase by approximately 30%, causing complete but temporary occlusion of
      cutaneous blood flow in this region. Significant, but normal, reactive hyperemia
      occurred upon release of the rib support pads (p < or = .05). Axial spinal
      unloading using an LTX 3000 induced changes in heart rate, blood pressure, and
      respiratory rates of magnitudes similar to those reported with the use of other
      traction devices. CONCLUSION: The forces applied to the rib cage by the LTX 3000
      for proper lumbar unloading caused changes in physiologic responses, but these
      changes were reversible and can be considered clinically unimportant and thus
      should not be contraindications to the use of this device by the general
      population.

PMID- 9596390
TI  - Is needle examination always necessary in evaluation of carpal tunnel syndrome?
AB  - OBJECTIVE: To investigate whether needle evaluation added any important clinical
      information to normal nerve conduction studies in the evaluation of carpal tunnel
      syndromes. DESIGN: Retrospective review of electromyography (EMG) done with the
      referring diagnosis of possible carpal tunnel syndrome. SETTING: Outpatients seen
      for EMG evaluation at one university hospital by a single electromyographer.
      PATIENTS: Consecutive sample of possible carpal tunnel syndrome patients.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE: We determined whether needle
      examination was abnormal when nerve conduction studies were normal. RESULTS: In
      patients in whom only carpal tunnel syndrome was suspected, normal nerve
      conduction studies predicted that EMG would be normal 89.8% of the time (p =
      .0494). Testing based on a larger sample size might increase the predictive
      value. CONCLUSIONS: There may be a subpopulation of patients referred for carpal
      tunnel syndrome who may be adequately evaluated by nerve conduction studies
      alone. Additional studies will help evaluate whether this is so.

PMID- 9596391
TI  - Functional magnetic stimulation for restoring cough in patients with tetraplegia.
AB  - OBJECTIVE: To evaluate the usefulness of functional magnetic stimulation (FMS) as
      a noninvasive method for assisting cough in patients with tetraplegia. DESIGN: A
      prospective before-after trial. SETTING: The functional magnetic stimulation
      laboratory of a spinal cord injury (SCI) service. PARTICIPANTS: Thirteen male SCI
      patients, with injury levels between C4 and C7. INTERVENTION: A commercially
      available magnetic stimulator with a round magnetic coil (MC) was used.
      Expiratory muscle activation was achieved by placing the MC along the lower
      thoracic spine. MAIN OUTCOME MEASURE: The planned major outcome measures were the
      maximal expired pressure (MEP), expiratory reserve volume (ERV), and forced
      expiratory flow rate (FEF) by FMS compared with voluntary maximal efforts.
      Another outcome was the optimal MC placement and stimulation intensity that would
      result in highest expired pressure. RESULTS: The mean (+/-SEM) MEP, ERV, and FEF
      generated by FMS were 66.40 +/- 6.69 cmH2O, .77 +/- .14 L, and 5.28 +/- .42
      L/sec, respectively. They were 118%, 169%, and 110% of voluntary maximum efforts.
      MC placement at the T10 to T11 spinous process and stimulation intensity at 80%
      produced the highest MEP and FEF. CONCLUSION: FMS of the expiratory muscles
      produced significant expired pressures, volumes, and flow rates when compared
      with voluntary maximum efforts; therefore, FMS can be used as an effective method
      to restore cough in tetraplegic patients.

PMID- 9596392
TI  - Cold effect on oxygen uptake, perceived exertion, and spasticity in patients with
      multiple sclerosis.
AB  - OBJECTIVE: To determine the effect of a cold bath (24 degrees C) on oxygen
      consumption and perceived exertion during ambulation and on spasticity in
      individuals with mild to moderate multiple sclerosis. DESIGN: A repeated-measures
      design with random assignment of experimental and control conditions. SETTING:
      Outpatient physical therapy department associated with an academic institution.
      PATIENTS: Fourteen individuals with clinically definite multiple sclerosis
      exhibiting spasticity and capable of ambulating at 0.7 m/sec on a motorized
      treadmill without handrail support. MEASUREMENT: Assessment of oxygen uptake,
      heart rate, and perceived exertion occurred during two 10-minute walks
      interspersed with a 30-minute rest on 2 separate days. Measurement of spasticity
      occurred three times during each session. RESULTS: Oxygen consumption and
      perceived exertion were unchanged. Spasticity was higher immediately (p < .05)
      after the cold bath. CONCLUSIONS: Increase in spasticity was statistically
      significant, but unlikely to be of any clinical importance. Contrary to our
      hypothesis, a cold bath (24 degrees C) for 20 minutes did not reduce oxygen
      consumption or rating of perceived exertion during ambulation.

PMID- 9596393
TI  - Gait characteristics of patients with claudication.
AB  - OBJECTIVE: Intermittent claudication of the lower extremity vessels produces pain
      during walking. This study differentiates walking patterns of patients with
      claudication from walking patterns of healthy individuals. DESIGN: Nonrandomized
      case control study performed in a teaching university hospital outpatient
      setting. PATIENTS: The sample of convenience involved male patients with lower
      extremity claudication (n = 19) and 11 healthy men of similar ages.
      INTERVENTIONS: Subjects were asked to walk at self-selected speed for 20 meters
      on a level, indoor surface. OUTCOME MEASURES: Walking velocity and number of
      steps were averaged over each of five trials, and step length was calculated from
      these measures. RESULTS: Patients with claudication walked slower and had
      decreased step length and decreased cadence compared with controls (p < .001). No
      positive relationship was found between disease severity, peak walking time, and
      step length, cadence, or speed. CONCLUSION: All patients with claudication,
      regardless of disease severity, demonstrated abnormal gait parameters compared
      with controls. Further studies should evaluate whether the abnormal gait
      parameters significantly curtail walking ability.

PMID- 9596394
TI  - Low-dose botulinum toxin with ankle taping for the treatment of spastic
      equinovarus foot after stroke.
AB  - OBJECTIVE: To evaluate the efficacy of a combined treatment for spastic foot
      using selective injections of botulinum toxin (BTA) into the tibialis posterior
      muscle followed by ankle taping, and to compare it with current BTA treatment
      procedure. DESIGN: Single-blind randomized control trial. Three-month follow-up
      after treatment. SETTING: Neurorehabilitation clinic. SUBJECTS: Eighteen
      outpatients with equinovarus foot due to severe spasticity after stroke.
      INTERVENTIONS: (1) Injection of 190 to 320 BTA U into several calf muscles (group
      A); (2) injection of 100 BTA U into the tibialis posterior muscle, followed by
      ankle-foot taping (group B). MAIN OUTCOME MEASURES: Ankle range of motion (ROM),
      Ashworth scale, gait velocity, and step length. RESULTS: Average Ashworth scores
      decreased 1 point in both groups, but the benefit appeared of shorter duration in
      group B. Changes in both foot position at rest and passive ankle ROM were
      observed in all patients, without treatment-related differences, except for gain
      in passive dorsiflexion that appeared higher in group A. Gait velocity and step
      length showed similar increases in both groups. CONCLUSION: The combination of
      selective injections of low BTA doses with ankle-foot taping is as effective as
      the injection of the current doses for the reduction of foot inversion with
      positive effects on gait parameters.

PMID- 9596395
TI  - Spectral electromyographic fatigue analysis of back muscles in healthy adult
      women compared with men.
AB  - OBJECTIVE AND DESIGN: To investigate the difference in back muscle endurance
      between normal adult women and men using surface electromyographic (EMG) power
      spectral analyses. METHODS: Forty-five healthy subjects (22 men and 23 women)
      were studied during an unsupported trunk holding test for 120 seconds. Recording
      surface electrodes were placed over each erector spinae muscle at L1 level.
      OUTCOME MEASURES: Median frequency (MF), mean power frequency (MPF), and zero
      crossing rate (ZCR) were evaluated using the ME3000P Fast Fourier Transform
      spectrum analysis program. The rate of change was determined for each parameter
      during the test, and correlation was examined by Pearson's correlation. RESULTS:
      The negative slopes of all indices of back muscle fatigue were significantly
      steeper in men than in women. CONCLUSION: Our results indicated that the trunk
      holding test combined with EMG power spectral analysis of lumbosacral muscles is
      useful for the evaluation of fatigue performance of these muscles. Our results
      also showed a higher muscle endurance in healthy adult women than in men.

PMID- 9596396
TI  - A 3-year follow-up of asthmatic patients participating in a 10-week
      rehabilitation program with emphasis on physical training.
AB  - OBJECTIVE: To determine if asthmatic patients who had participated in a 10-week
      rehabilitation program with emphasis on physical training (1) continued with
      physical training, (2) maintained their improved cardiovascular condition and
      lung function, and (3) retained their good asthma control through the following 3
      years. DESIGN: A descriptive 3-year follow-up study. PATIENTS AND SETTING: A
      convenience sample of 58 patients who had previously undergone a 10-week
      outpatient rehabilitation program were followed up 6 months and 1, 1.5, 2, and 3
      years after the start of the program at a lung clinic in a university hospital.
      MAIN OUTCOME MEASURES: A training log was kept by each patient to record
      frequency, intensity, and mode of training. Physical condition was evaluated with
      a submaximal 6-minute ergometry test and a 12-minute walking test, respiratory
      function with static and dynamic spirometry, and bronchial hyperreactivity with a
      metacholine provocation test. Asthma symptoms and asthma control were measured
      with a study-specific questionnaire. RESULTS: Thirty-nine subjects (68%)
      exercised regularly during all 3 years. The cardiovascular condition and lung
      function values remained almost unchanged in all 58 patients. There was a
      significant decrease in number of emergency room visits the year after the 10
      week rehabilitation program compared to the year before. It remained stable
      throughout the following 2 years. There was also a decrease in asthma symptoms in
      all patients, but the decrease was significant only in a subgroup of 26 patients,
      who exercised one or two times a week. CONCLUSIONS: It is possible for asthmatic
      subjects to exercise at a moderate intensity level on a long-term basis without
      deleterious effects. Moreover, the high compliance rate might indicate that
      inactive asthmatic patients who are taught how to exercise choose to continue to
      be physically active.

PMID- 9596397
TI  - Velopharyngeal airway resistance disorders after traumatic brain injury.
AB  - OBJECTIVE: Disorders affecting velopharyngeal port closure may result in the
      perception of hypernasality. This study was designed to determine (1) the
      incidence of velopharyngeal airway resistance deficits after traumatic brain
      injury, (2) the relation between velopharyngeal airway resistance and dysarthria
      severity, and (3) the relation between velopharyngeal airway resistance and
      perceived hypernasality. DESIGN: Case series. SETTING: Community re-entry
      residential rehabilitation program. PATIENTS: Eighty-three consecutive referrals
      for speech production evaluations. MAIN OUTCOME MEASURES: Velopharyngeal airway
      resistance at the time of the evaluation. RESULTS: About half the patients
      evidenced reduced velopharyngeal airway resistance. Subjects who evidenced mild
      or absent dysarthria typically had no velopharyngeal deficits, while subjects who
      evidenced severe dysarthria had very low velopharyngeal airway resistance. With
      few exceptions, the severity of the velopharyngeal airway resistance deficit was
      associated with perceived hypernasality. CONCLUSIONS: Velopharyngeal airway
      resistance disorders after traumatic brain injury are common. Discrepancies
      between velopharyngeal airway resistance and perceived hypernasality may be
      caused by intelligibility, speaking style, or nonrepresentative sampling.

PMID- 9596398
TI  - Head injury in young adults: long-term outcome.
AB  - OBJECTIVE: To describe the long-term outcome 5 years after injury of young adults
      who were 15 to 19 years old at the time of their head injuries. DESIGN: A
      retrospective cohort. The health records of 62 consecutive eligible subjects were
      abstracted for baseline sociodemographic, health, and injury variables. A
      telephone interview was administered to assess quality of life, impairment,
      disability, and handicap. SETTING: Canada's largest trauma center, Sunnybrook
      Health Science Centre, Toronto, Canada. SUBJECTS: Of the 58 subjects (94%) who
      were traced at follow-up, 51 agreed to participate. MAIN OUTCOME MEASURES: The
      Medical Outcomes Study SF-36, Head Injury Symptom Checklist, selected disability
      measures, Community Integration Questionnaire. RESULTS: Of the 8 summary items of
      the Medical Outcomes Study SF-36, subjects scored lowest on mental health. There
      were no significant differences between mild and more severely injured groups in
      all quality of life measures. Subjects classified with mild head injury overall
      reported more symptoms from the Head Injury Symptom Checklist. Subjects with more
      severe injuries had lower community integration scores (p < .05). CONCLUSIONS:
      Overall, mental health is an important area of concern at follow-up for all
      subjects. Adolescents with apparent mild head injury can have disabling symptoms
      many years after injury.

PMID- 9596399
TI  - Health-related fitness test battery for adults: associations with perceived
      health, mobility, and back function and symptoms.
AB  - OBJECTIVE: To evaluate the health-related content validity of nine fitness tests
      by studying how low, mid, and high levels of fitness are associated with
      perceived health and musculoskeletal functioning. DESIGN: Cross-sectional
      methodological study. SETTING: A research institute for health promotion.
      PARTICIPANTS: Middle-aged (37 to 57 years) men (n = 245) and women (n = 253),
      evenly selected from five age cohorts of a random population sample. MAIN OUTCOME
      MEASURES: The odds ratios (ORs) of selected health outcomes for low (least fit
      20%), mid (next 40%), and high (most fit 40%) fitness categories in the different
      tests adjusted for several possible confounders. RESULTS: Cardiorespiratory
      fitness, as measured by 2-km walk test, was strongly and consistently associated
      with perceived health and mobility (stair climbing) in both genders (range of
      ORs, 2.4 to 17.6), and a somewhat weaker relationship was found with leg power
      and with leg strength (ORs, 2.5 to 7.2). Low fitness in back muscular endurance
      and upper-body strength were associated with mobility disability (ORs, 2.8 to
      8.5) and with back dysfunction and pain (ORs, 2.9 to 6.1). High fitness in back
      endurance in men and in balance in women were related to positive back health
      (ORs, 2.5 to 3.7). Body mass index was associated with musculoskeletal disability
      in women (ORs, 2.4 to 5.3). Balance, leg strength, and leg flexibility in men;
      and leg power, trunk and leg flexibility in women were not associated with health
      outcomes. CONCLUSIONS: Among a middle-aged population, the majority of the
      evaluated fitness tests demonstrated health-related validity by strong
      associations with perceived health and musculoskeletal functioning, and by weaker
      associations with back symptoms.

PMID- 9596400
TI  - Electromyogram-triggered neuromuscular stimulation for improving the arm function
      of acute stroke survivors: a randomized pilot study.
AB  - OBJECTIVE: To assess the efficacy of electromyogram (EMG)-triggered neuromuscular
      stimulation (EMG-stim) in enhancing upper extremity motor and functional recovery
      of acute stroke survivors. DESIGN: A pilot randomized, single-blinded clinical
      trial. SETTING: Freestanding inpatient rehabilitation facility. PATIENTS: Nine
      subjects who were within 6 weeks of their first unifocal, nonhemorrhagic stroke
      were randomly assigned to either the EMG-stim (n = 4) or control (n = 5) group.
      All subjects had a detectable EMG signal (>5 microV) from the surface of the
      paretic extensor carpi radialis and voluntary wrist extension in synergy or in
      isolation with muscle grade of <3/5. INTERVENTION: All subjects received two 30
      minute sessions per day of wrist strengthening exercises with EMG-stim
      (experimental) or without (control) for the duration of their rehabilitation
      stay. MAIN OUTCOME MEASURES: Upper extremity Fugl-Meyer motor assessment and the
      feeding, grooming, and upper body dressing items of the Functional Independence
      Measure (FIM) were assessed at study entry and at discharge. RESULTS: Subjects
      treated with EMG-stim exhibited significantly greater gains in Fugl-Meyer (27.0
      vs 10.4; p = .05), and FIM (6.0 vs 3.4; p = .02) scores compared with controls.
      CONCLUSION: Data suggest that EMG-stim enhances the arm function of acute stroke
      survivors.

PMID- 9596401
TI  - Deep vein thrombi associated with the use of plastic ankle-foot orthoses.
AB  - Deep vein thrombosis (DVT) is a well-known complication of neurologic disorders
      that result in immobility, such as stroke and spinal cord injury. There is little
      information available, however, regarding the association of DVT with orthotic
      devices commonly used in this patient population. We report an unusual case in
      which lesser saphenous vein DVTs were associated with the use of plastic ankle
      foot orthoses (PAFOs) in a patient with chronic inflammatory demyelinating
      polyradiculoneuropathy treated with plasmaphoresis and intravenous Ig. The
      possible role of PAFOs in the development of the DVTs, as well as other
      contributing factors such as plasmaphoresis, is discussed. The need for
      posthospitalization DVT prophylaxis in patients with paralysis is reviewed.

PMID- 9596402
TI  - Flashback and nightmares after surgery under neuraxial anesthesia: a report of
      two cases.
AB  - Recall, awareness, flashback, and nightmares are reported complications of
      general anesthesia, but flashback and nightmares after regional anesthesia have
      not been described. Two patients underwent vascular and orthopedic surgery under
      spinal and epidural anesthesia, respectively. Local anesthetic consisted of
      bupivacaine, and sedation was achieved with the combination of fentanyl,
      midazolam, and diphenhydramine. In both patients the anesthetic course was
      uneventful, but the recovery process was complicated by flashbacks and nightmares
      leading to depression, physical complaints, and lengthy convalescence. Flashback
      and nightmares after neuraxial anesthesia are unreported and, therefore, their
      incidence is unknown.

PMID- 9596403
TI  - Beta blockade in the treatment of autonomic dysreflexia: a case report and
      review.
AB  - Autonomic dysreflexia has long been considered a sympathetically mediated
      phenomenon. Recent articles have reported the use of alpha blockers as a means of
      treatment. We report the case of a 20-year-old C5 American Spinal Injury
      Association A spinal cord injured patient who almost daily experienced symptoms
      of headache, facial flushing, and hypertension consistent with autonomic
      dysreflexia. These symptoms caused him frequent discomfort and anxiety. Despite
      an extensive workup, we were unable to identify a source of his dysreflexic
      episodes. After starting metoprolol 50 mg every night, however, these episodes
      stopped and the patient showed no adverse effects from the medication.

PMID- 9596404
TI  - Successful prosthetic fitting of a 73-year-old hip disarticulation amputee
      patient with cardiopulmonary disease.
AB  - Patients with hip disarticulation (HD) require high energy expenditure for
      successful prosthetic ambulation. Thus, older patients are rarely fitted with an
      HD prosthesis. To our knowledge there are no reports of gait analysis following
      successful prosthetic fitting of an elderly HD amputee patient with systemic
      cardiopulmonary disease. We report the case of successful prosthetic ambulation
      in a 73-year-old man with HD secondary to histiosarcoma and a medical history
      significant for stable angina, chronic obstructive pulmonary disease, and
      diabetes mellitus. The patient underwent gait training with an endoskeletal
      prosthesis and achieved ambulation to 400 feet with bilateral forearm crutches.
      Vicon kinematic gait analysis revealed a cadence of 44 steps/min (112 steps/min
      normal), and double support time of 47% (26% normal). Oxygen rate during
      ambulation (VO2) was 11.0 mL/kg/min at velocity of .35 m/sec, compared with
      published figures for ambulation in those with HD of 10.73 mL/kg/min at velocity
      of .93 m/sec. At 1-year follow-up, the patient continued to walk into church with
      the prosthesis. We conclude that a trial fitting of an HD prosthesis should be
      considered on an individual basis in elderly amputee patients.

PMID- 9596405
TI  - An aggressive approach to limb dystonia: a case report.
AB  - A 15-year-old boy presented with a severe fluctuating foot and ankle dystonia
      resulting from a basal ganglia insult at the age of 4. This followed an embolic
      event related to an undiagnosed prolapsed mitral valve. Functionally, the patient
      was ambulatory with rocker bottom crutches and an ankle-foot orthosis, but there
      were periods of up to a year when pain and increased dystonic deformity required
      him to use a wheelchair. A new orthotic was made nearly every month because the
      orthotist could find no material that would withstand his tone without breaking,
      yet he could not ambulate without one. Multiple interventions, including
      biofeedback, contrast baths, stretching and strengthening, oral lioresal
      (Baclofen), diazepam (Valium), benztropine mesylate (Cogentin), carbidopa
      levodopa (Sinemet), carbamazepine (Tegretol), and injections of botulism toxin
      (BOTOX) were tried, all with minimal effects. Amputation was recommended, based
      on anatomic and functional considerations. The patient and his family adjusted
      well to this decision, although not all orthopedists and therapists adjusted
      easily to the choice. The patient is now functionally independent with a
      prosthesis and has a normal teenage lifestyle for the first time.

PMID- 9596406
TI  - Topical capsaicin as an adjuvant analgesic for the treatment of traumatic amputee
      neurogenic residual limb pain.
AB  - The treatment of amputee residual limb pain can at times be a challenge for the
      physician. Occasionally, traditional analgesic medication regimens cannot be used
      or are ineffective in relieving the pain. Topical capsaicin cream has been a
      beneficial adjuvant medication in the treatment of some painful conditions. The
      authors present three patients with traumatic upper limb amputations where
      topical capsaicin cream was of benefit in the treatment of neurogenic residual
      limb pain. The hope is that these cases will increase awareness of the potential
      use of capsaicin cream as an adjuvant analgesic in patients with residual limb
      pain. Common causes of residual limb pain and the pharmacology of capsaicin cream
      are discussed.

PMID- 9596407
TI  - Practice parameter: antiepileptic drug treatment of posttraumatic seizures. Brain
      Injury Special Interest Group of the American Academy of Physical Medicine and
      Rehabilitation.
AB  - The practice of antiepileptic drug (AED) prophylaxis for posttraumatic seizures
      (PTS) is common, although results of clinical trials raise questions regarding
      the benefits of such treatment. A subcommittee of the Brain Injury Special
      Interest Group of the American Academy of Physical Medicine and Rehabilitation
      was impaneled to review published literature regarding AED prophylaxis of PTS and
      formulate recommendations in the form of a practice parameter. The subcommittee
      presents the following recommendations: (1) Treatment standard: Prophylactic use
      of phenytoin (PHT), carbamazepine (CBZ), sodium valproate (VPA), or phenobarbital
      (PB) is not recommended for preventing late PTS, defined as seizures that occur
      after 1 week of injury, in the patient in whom there has been no history of
      seizures following a nonpenetrating traumatic brain injury (TBI). (2) It is
      recommended as a treatment option that PHT, PB, and CBZ may be used to prevent
      early PTS in patients at high risk for seizures following TBI. (3) Prophylactic
      use of PHT, CBZ, VPA, or PB is not recommended for preventing late PTS following
      penetrating TBI.

PMID- 9596408
TI  - Huntington disease.

PMID- 9596409
TI  - Sequential expression of transforming growth factor-beta1 by T-cells,
      macrophages, and microglia in rat spinal cord during autoimmune inflammation.
AB  - Transforming growth factor-beta1 (TGF-beta1) is crucially involved in regulating
      inflammatory events during experimental autoimmune encephalomyelitis (EAE), an
      animal model for multiple sclerosis. Despite accumulating evidence for local
      expression of TGF-beta1 in the inflamed nervous system, uncertainty remains
      regarding its cellular source. We have investigated the temporospatial
      distribution of TGF-beta1 gene expression in rat spinal cord during EAE. In
      actively induced EAE, in situ hybridization revealed strong expression of TGF
      beta1 in meningeal and perivascular mononuclear infiltrates at onset of the
      disease, continued expression in perivascular infiltrates and scattered
      mononuclear cells at maximal disease severity, and expression in scattered
      parenchymal cells during recovery. Double labeling studies revealed
      subpopulations of infiltrating T-cells to be the major source of TGF-beta1 early
      in the disease, followed by macrophages at peak severity and microglial cells
      during the recovery phase of EAE. Astrocytes and neurons did not express TGF
      beta1. Quantification of mRNA by Northern blot analysis revealed that cellular
      expression of TGF-beta1 by T-cells, macrophages, and microglia sums up to a long
      lasting elevation of TGF-beta1 mRNA extending well into the recovery phase. Our
      data indicate cellular diversity and suggest functional diversity of TGF-beta1
      gene expression during EAE. While TGF-beta1 expressed early in the disease by T
      cells may contribute to inflammatory lesion development, microglial cells may
      potentially contribute to recovery by expressing immunosuppressive TGF-beta1
      during remission.

PMID- 9596410
TI  - Characterization of the mitochondrial DNA abnormalities in the skeletal muscle of
      patients with inclusion body myositis.
AB  - Inclusion body myositis (IBM) is a late-onset inflammatory myopathy with
      distinctive clinical and histopathological features. The molecular basis for the
      disease remains unknown, but abnormal nuclear morphology and the accumulation of
      a protein that binds single-stranded DNA in a sequence-independent fashion
      suggest a nuclear defect. Evidence of mitochondrial respiratory chain dysfunction
      (ragged-red fibers, multiple mtDNA deletions) has been reported in IBM muscle.
      Here we have investigated the relationship of the mtDNA abnormalities in sporadic
      and familial IBM patients to the pathogenesis of the disease. In situ
      hybridization analysis with mtDNA probes revealed several different mtDNA
      abnormalities in cytochrome c oxidase-negative muscle fibers including large
      scale mtDNA deletions and mtDNA depletion, but no evidence for nonspecific DNA
      binding. Contrary to previous reports, we did not observe mtDNA deletions on
      Southern blot analysis, consistent with the presence of multiple different
      deleted mtDNA species demonstrated by single fiber PCR. There was no consistent
      correlation between the mitochondrial abnormalities and markers of muscle
      regeneration, inflammation, or microscopically detectable pathological
      alterations of myonuclei in the same fibers. Thus, early molecular abnormalities
      in IBM may simply accelerate the accumulation of mtDNA abnormalities that occurs
      with natural aging.

PMID- 9596411
TI  - Glut1 glucose transporter in the primate choroid plexus endothelium.
AB  - The objective of the present study was to define the cellular location of the
      Glut1 glucose transporter in the primate choroid plexus. Immunogold electron
      microscopy indicated that Glut1 epitopes were associated primarily with choroid
      plexus endothelial cells. Digitized analyses of electron microscopic images
      provided quantitative estimates of the relative number of Glut1 glucose
      transporter epitopes on luminal and abluminal endothelial cell membranes within
      the choroid plexuses. We recorded a high density of Glut1 in the microvascular
      endothelium of primate choroid plexus, which was consistent in vervet monkeys (5
      10 Glut1 gold particles per micrometer of endothelial cell plasma membrane), as
      well as in baboons (5-20 Glut1 gold particles per micrometer of capillary plasma
      membrane). In the baboon choroid plexus, we observed that perivascular cells
      (presumed to be pericytes) were also Glut1-positive, but with substantially
      reduced activity compared with endothelial cells. Occasional Glut1-immunogold
      particles were also seen in the basolateral membranes of the choroid plexus
      cuboidal cells. Light microscopic immunocytochemistry confirmed the abundance of
      Glut1 immunoreactivity in choroid plexus endothelial cells of vervet monkeys and
      baboons. A similar pattern was observed in surgically resected human choroid
      plexus, suggesting differences between primates, including humans and laboratory
      animals. The only difference was that erythrocytes within the human choroid
      plexus exhibited a florid Glut1-positive response, but were weakly immunoreactive
      in nonhuman primates. The observation of high glucose transporter densities in
      choroid plexus endothelial cells is consistent with the suggestion that choroidal
      epithelia and capillaries provide a metabolic work capability for maintaining
      ionic gradients and secretory functions across the blood-CSF barriers.

PMID- 9596412
TI  - Distribution of reducible 4-hydroxynonenal adduct immunoreactivity in Alzheimer
      disease is associated with APOE genotype.
AB  - Two major risk factors for late-onset familial and sporadic Alzheimer disease
      (AD), a leading cause of dementia worldwide, are increasing age and inheritance
      of the epsilon4 allele of the apolipoprotein E gene (APOE4). Several isoform
      specific effects of apoE have been proposed; however, the mechanisms by which
      apoE isoforms influence the pathogenesis of AD are unknown. Also associated with
      AD is increased lipid peroxidation in the regions of the brain most damaged by
      disease. 4-hydroxynonenal (HNE), the most potent neurotoxic product of lipid
      peroxidation, is thought to be deleterious to cells through reactions with
      protein nucleophiles. We tested the hypothesis that accumulation of the most
      common forms of HNE-protein adducts, borohydride-reducible adducts, is associated
      with AD and examined whether there was a relationship to APOE. Our results
      demonstrated that reducible HNE adducts were increased in the hippocampus,
      entorhinal cortex, and temporal cortex of patients with AD. Furthermore, our data
      showed that the pattern of reducible HNE adduct accumulation was related to APOE
      genotype; AD patients homozygous for APOE4 had pyramidal neuron cytoplasmic
      accumulation of reducible HNE adducts, while AD APOE3 homozygotes had both
      pyramidal neuron and astrocyte accumulation of reducible HNE adducts. This is in
      contrast to our previous observations that a distinct HNE protein adduct, the
      pyrrole adduct, accumulates on neurofibrillary tangles in AD patients. We
      conclude that APOE genotype influences the cellular distribution of increased
      reducible HNE adduct accumulation in AD.

PMID- 9596413
TI  - Chronic relapsing experimental autoimmune encephalomyelitis: effects of insulin
      like growth factor-I treatment on clinical deficits, lesion severity, glial
      responses, and blood brain barrier defects.
AB  - Chronic relapsing experimental autoimmune encephalomyelitis (crEAE), a model for
      multiple sclerosis, was used to test 2 regimens of insulin-like growth factor-I
      (IGF-I) treatment. We induced crEAE by injecting 3x10(7) myelin basic protein
      (MBP) sensitized lymph node cells into adult female SJL/J mice. Fifty-one mice,
      divided randomly into 4 groups, were used in the first trial. Two groups received
      IGF-I (a gift of Cephalon, Inc.) 0.6 mg/kg/d subcutaneously from day 7 to day 16
      and the other two groups received placebo injections. IGF-I treatment reduced
      clinical deficits during the first attack and during 2 subsequent relapses. Image
      analysis of immunostained and histological sections showed that IGF-I treatment
      reduced BBB defects and both the numbers and sizes of inflammatory,
      demyelinating, and demyelinated lesions. Twelve mice that had recovered from
      their first attack were used in our second trial to evaluate possible adverse
      effects of prolonged treatment with a higher dose of IGF-I. Six received 1.2
      mg/kg/d for 6 weeks (days 19-63). No adverse effects of IGF-I treatment were
      identified. The eyes, hearts, livers, and kidneys of IGF-I-treated mice were
      normal histologically and their spleens also appeared normal except for mild to
      moderate microscopic increases in lymphopoesis. Our results suggest that
      prolonged IGF-I treatment is well tolerated and that the anti-inflammatory
      effects of IGF-I have a major role in reducing clinical deficits and lesion
      severity in crEAE. These effects, if present in multiple sclerosis, may benefit
      patients with this disease.

PMID- 9596414
TI  - Tropoelastin and elastin degradation products promote proliferation of human
      astrocytoma cell lines.
AB  - Expression of tropoelastin, the precursor of insoluble elastin and a major
      component of elastic fibers, has not yet been demonstrated in astrocytomas nor
      has it been linked to their proliferation. Here we report that human astrocytoma
      cell lines (U87 MG, U251 MG, U343 MG-A, U373 MG, SF 126, SF188, SF 539), as well
      as surgical specimens of malignant human astrocytomas, express intracellular
      tropoelastin. The tropoelastin produced by astrocytoma cells is, however,
      susceptible to proteolytic trimming to the extent that it cannot be assembled
      into extracellular elastic fibers. Astrocytoma cells also express the cell
      surface 67-kDa elastin binding protein (EBP), which binds elastin degradation
      products, leading to the upregulation of cyclin A and cdk2 and increased
      incorporation of [3H]-thymidine. The elastin-dependent mitogenic response of
      astrocytoma cells is abolished by lactose and chondroitin sulfate, factors which
      cause shedding of this 67-kDa elastin receptor from the cell surface and by
      blocking anti-EBP antibody. We therefore suggest that, in astrocytomas,
      endogenous tropoelastin degradation products bind to EBP and generate signals
      leading to cell cycle progression in an autocrine or paracrine manner. This is
      the first report implicating elastin-derived peptides as possible mitogens in
      malignant astrocytomas.

PMID- 9596415
TI  - Altered gene expression in human astrocytoma cells selected for migration: I.
      Thromboxane synthase.
AB  - Human glioma cells from a long-term cell line were selected for their ability to
      migrate on a glioma-derived extracellular matrix. When tested over 28 serial
      passages, the migration-selected strain showed a genetically stable, enhanced
      migration rate compared with the parental cells. Proliferation studies
      demonstrated that the growth rate of migration-selected cells was slightly
      arrested. Both the selected strain and the parental culture showed anchorage
      independent growth in soft agarose and were tumorigenic in athymic mice. Using
      molecular genetic strategies' display to isolate genes expressed differentially
      between the 2 populations, a 300-bp sequence homologous to thromboxane synthase
      was upregulated in the migration-selected cells relative to the parental cells.
      Expression levels of thromboxane synthase were highly elevated in the migration
      selected cells when assessed by RNAse-protection assay and by flow cytometry. Two
      specific thromboxane synthase inhibitors, Dazmegrel and Furegrelate, reduced the
      migration rate of the migration-selected cells to a rate equal to or less than
      the rate exhibited by the parental cells, respectively. The inhibitors effect on
      the parental cells was inconsequential. These results suggest that aberrations in
      the regulation of thromboxane synthase expression or activity may influence the
      motility of human glioma cells.

PMID- 9596416
TI  - Alzheimer disease: DNA fragmentation indicates increased neuronal vulnerability,
      but not apoptosis.
AB  - Although nerve cell loss is prominent in certain brain regions in Alzheimer
      disease (AD), it is currently unresolved how these cells die. Recent studies
      unanimously agree that there are more neurons displaying DNA fragmentation in AD
      compared with normal controls. However, controversy remains as to whether cell
      death is mediated by apoptosis or necrosis. We addressed this question by
      comparing AD lesions with those from cases with pontosubicular neuron necrosis
      (PSNN), a human pathological condition with unequivocal neuronal apoptosis, with
      regard to cell and nuclear morphology, immunohistochemistry, and in situ tailing.
      Immunohistochemistry was performed for an array of proteins with presumptive
      roles in the apoptotic process or the protection thereof, i.e. a recently
      described apoptosis-specific protein (ASP), the transcription factor c-Jun, Bcl
      2, and various stress proteins: alpha B-Crystallin, heat shock protein (HSP) 27,
      HSP 65, HSP 70, HSP 90, and ubiquitin. Apoptotic neurons in PSNN displayed
      chromatin condensation, nuclear fragmentation, and cytoplasmic condensation. They
      were labeled with the in situ tailing technique and stained for the ASP. Despite
      the large numbers of cells with DNA fragmentation identified in the hippocampus
      of AD brains, only exceptional cells displayed the morphological characteristics
      of apoptosis or labeled for the ASP. We suggest that the increased rate of
      neuronal DNA fragmentation in AD patients indicates a higher susceptibility of
      the cells to metabolic disturbances compared with normal controls. The large
      number of cells with DNA fragmentation most likely reflects metabolic
      disturbances in the premortem period, and cell destruction is mediated through
      necrosis rather than apoptosis.

PMID- 9596417
TI  - Commentary on "Neuropathologic evidence that the Lewy body variant of Alzheimer
      disease represents coexistence of Alzheimer disease and idiopathic Parkinson's
      disease (1998;57:39-46)".

PMID- 9596419
TI  - Value of computed tomography in the evaluation of retroperitoneal organ injury in
      blunt abdominal trauma.
AB  - Computed tomography (CT) is widely used in the evaluation of blunt abdominal
      trauma. One of its purported advantages is in the evaluation of the
      retroperitoneum. This study was undertaken to determine the utility of CT in
      diagnosing retroperitoneal organ injury. A retrospective chart review of 466
      stable patients with blunt abdominal trauma who received abdominal CT was
      conducted. Twelve percent of the patients had CT scans showing retroperitoneal
      organ injury. There were 58 total injuries, with the kidney being the most
      frequently injured organ. Twenty-four patients required laparotomy, confirming
      the CT diagnosis in 8 patients (7 renal and 1 pancreatic). Two duodenal injuries
      were found at laparotomy that had not been seen on CT scan. Fourteen percent of
      the patients with positive CT scans had a positive laparotomy, and of those, 38%
      were therapeutic. Five percent of the patients with positive scans had
      therapeutic laparotomies. These data infer that the utility of CT to define
      retroperitoneal organ injury is lower than previously suspected.

PMID- 9596418
TI  - High-dose nitrates in the immediate management of unstable angina: optimal
      dosage, route of administration, and therapeutic goals.
AB  - Nitrates are commonly used for rapid relief of ischemia in the initial management
      of unstable angina. However, their optimal dosage, route of administration, and
      therapeutic goals have not been fully established. This study was conducted to
      determine the optimal dosage and mode of administration (intravenous bolus versus
      sublingual spray) of nitrates and the therapeutic goals of their use in the
      immediate management of unstable angina. In a single-center prospective trial, 72
      consecutive patients with unstable angina accompanied by typical ST-segment
      depression on electrocardiogram were randomly assigned to receive isosorbide
      dinitrate either as repeated intravenous boluses or as sublingual sprays while
      being delivered to the hospital by a mobile intensive care unit. Optimal nitrate
      dosage was tailored to pain relief while monitoring mean blood pressure reduction
      to an optimal range (5% to 20%) without dosage restriction. The mean nitrate
      dosage needed for ischemia control during the first hour of treatment was 7.8 +/-
      3.8 mg. Optimal blood pressure reduction was achieved by significantly more
      intravenously treated patients than sublingually treated patients (68% v 41%, P =
      .037). Intravenously treated patients also experienced a more pronounced
      therapeutic effect, as assessed by reduction in chest pain score (67% v 39%, P =
      .0004) and decrease in ST-segment depressions (57% v 27%, P = .004). These
      results show that higher doses of nitrates than previously recommended are
      required for ischemia control during the initial management of unstable angina.
      The use of repeated intravenous boluses is safe and more easily controlled and,
      therefore, more efficacious than sublingual sprays in inducing the maximal anti
      ischemic effect while avoiding significant hypotension.

PMID- 9596420
TI  - Cofactors of alcohol-related trauma at a rural trauma center.
AB  - To analyze the cofactors of alcohol-related trauma at a rural, Level II trauma
      center, 127 admitted trauma patients were interviewed about psychological
      problems, social factors, and medical histories. Patients were divided into two
      groups, blood alcohol content (BAC) positive and BAC negative, for analysis.
      Seventy-one patients (56%) were BAC negative; 56 (44%) were BAC positive. Forty
      three of the 82 males (52%) had positive BAC tests, compared with 13 of the 45
      females (29%) (P = .01). Fifty-one of the 56 BAC-positive patients (91%) were
      aged 21 to 50 years, compared with 29 of the 71 BAC-negative patients (41%) (P =
      .0001). Ten of the 12 patients (83%) who were recently unemployed were BAC
      positive, compared with 46 of the 115 patients (40%) who were not recently
      unemployed (P = .004). Eleven of the 12 patients (92%) with positive drug screens
      were BAC positive, compared with 45 of the 115 patients (39%) with negative drug
      screens (P = .0005). These results show that there are important cofactors of
      alcohol-related trauma in rural areas.

PMID- 9596421
TI  - Time series forecasts of ambulance run volume.
AB  - To test the hypothesis that time series analysis can provide accurate predictions
      of future ambulance service run volume, a prospective stochastic time series
      modeling study was conducted at a community-based regional ambulance service. For
      all requests for ambulance transport during two sequential years, the time and
      date, total run time, and acuity code of the run were recorded in a computer
      database. Time series variables were formed for ambulance service runs per hour,
      total run time, and acuity. Prediction models were developed from one complete
      year's data (1994) and included four model types: raw observations, moving
      average, means with moving average smoothing, and autoregressive integrated
      moving average. Forecasts from each model were tested against observations from
      the first 24 weeks of the subsequent year (1995). Each model's adequacy was
      tested on residuals by autocorrelation functions, integrated periodograms, linear
      regression, and differences among the variances. A total of 68,433 patients were
      seen in 1994 and 32,783 in the first 24 weeks of 1995. Large periodic variations
      in run volume with time of day were found (P < .001). A model based on arithmetic
      means of each hour of the week with 3-point moving average smoothing yielded the
      most accurate forecasts and explained 54.3% of the variation observed in the 1995
      test series (P < .001). Time series analysis can provide powerful, accurate short
      range forecasts of future ambulance service run volume. Simpler, less expensive
      models performed best in this study.

PMID- 9596422
TI  - Continuous flumazenil infusion in preventing complications arising from severe
      benzodiazepine intoxication.
AB  - A prospective, randomly controlled study was conducted to test the effect of
      continuous flumazenil infusion in preventing complications arising from severe
      benzodiazepine (BZ) intoxication. Patients who were believed to be suffering
      benzodiazepine intoxication and whose Glasgow Coma Scale (GCS) score was below 10
      were enrolled after showing a clear-cut response to flumazenil 0.5 or 1 mg (an
      improvement by 4 or more on the GCS). The patients were consecutively enrolled
      and randomized into two groups: a continuous infusion group (CI, n = 50) who were
      immediately given flumazenil 0.5 mg/h for 5 hours, and a control group (CIN, n =
      50). Age, sex, incidence of underlying disease, GCS score at several time points,
      and complication rate were compared in the two groups. Although the CI group had
      a higher GCS score at most time points, the complication rate did not
      significantly differ between the two groups (14 of 36 in the CI group v 12 of 38
      in the CIN group, P = .684). A greater incidence of underlying disease and an
      older age seemed to contribute to the higher complication rates in both groups.
      Several patients (in both groups) resedated into deeper coma after showing an
      initial response to flumazenil or after the cessation of flumazenil infusion. For
      severe BZ intoxication, treatment with flumazenil infusion should still be
      considered skeptically and should not be recommended as routine management BZ
      intoxicated patients with an underlying disease, an older age, and resedation
      into a deep comatose state after showing an initial response to flumazenil should
      be treated in an intensive care unit.

PMID- 9596423
TI  - Large-diameter suction tubing significantly improves evacuation time of simulated
      vomitus.
AB  - Current suction equipment is often inadequate at clearing the oropharynx. This
      study tested the hypothesis that evacuation times of simulated vomitus could be
      significantly improved by increasing suction tube and connection port diameters.
      Two standard suction systems and a new large-diameter suction system were tested.
      Mean evacuation times for 90 mL (an average mouthful) of three different vomitus
      simulating substances--water, activated charcoal, and Progresso vegetable soup-
      were compared. All parameters other than suction tubing and attachment port
      diameters remained constant. The data were analyzed with analysis of variance and
      Fisher's protected least significant difference post hoc test. Use of large
      diameter suction tubing significantly (P < .0001) improved evacuation time for
      each of the three substances. This improvement was most evident in the trials
      with activated charcoal and the vegetable soup, where there was a tenfold
      decrease in mean evacuation time. These results show that large-diameter 3/4-inch
      suction tubing connected to the 1-inch port is superior to the standard 1/4-inch
      tubing and connection ports currently used. The tenfold reduction in evacuation
      time of viscous and particulate materials may have important clinical
      implications in preventing or minimizing complications from aspiration.

PMID- 9596424
TI  - Impact of emergency medicine residents on ancillary test utilization.
AB  - The effect of the addition of emergency medicine residency on the use of
      ancillary testing in a teaching hospital's emergency department (ED) staffed
      previously by emergency medicine board-certified physicians was studied.
      Prospectively, the utilization of three common ancillary tests (electrolyte
      levels, X-ray, or electrocardiogram) for four common chief complaints of patients
      eventually discharged from the ED was evaluated. A 12-month period before and a
      15-month period after introduction of an emergency medicine residency program
      were compared. The mean number of ancillary tests utilized by the ED attending
      physicians working with residents was compared with the mean number of tests
      generated by the same physicians (all emergency medicine board-certified) for the
      same complaints in the year before the residents' arrival. There was no
      significant difference in test use before and after introduction of the residency
      (P = .66). Faculty use of tests was also unaffected by the concurrent presence of
      residents (P = .068). These results show that the use of testing for a sample of
      common ED complaints was not affected by the introduction of emergency medicine
      residents to a previously emergency medicine board-certified staff in one
      community teaching hospital.

PMID- 9596425
TI  - Response times and outcomes for cardiac arrests in Las Vegas casinos.
AB  - This study was conducted to measure emergency medical services (EMS) response
      times in sudden out-of-hospital cardiac arrests and relate those times to
      probability of survival in cardiac arrest victims in Las Vegas casino-hotels from
      January 1993 to June 1996. Times from 911 activation to casino arrival and casino
      arrival to arrival at patient's side (time to first defibrillatory shock), as
      well as survival to hospital discharge, were studied with regression analysis.
      Sixty patients survived (29.3%). Response times to the hotels for survivors and
      nonsurvivors were similar (4.8 v 5.6 min, P = .44). However, times from arrival
      at the casino to arrival at the patient's side (5.0 v 6.88 min, P = .01) and
      elapsed times from 911 activation until first shock (9.88 v 12.46 min, P = .02)
      were substantially longer for nonsurvivors. Model fitting disclosed that with a
      911-to-shock time of 4 minutes, survival probability was 36%. Odds decreased by
      5% each minute, to 19% after 23 minutes. Ventricular fibrillation was the most
      common initial rhythm (187 cases) and was associated with the shortest times from
      911 to shock (10.7 +/- 7.8 min). There was a strong trend to increased survival
      with ventricular fibrillation. The 911-to-shock times in this study are
      considerably better than in other published reports for large metropolitan EMS
      systems, but the time from 911 to shock was nearly 3 minutes longer for
      nonsurvivors, and even those defibrillated at 4 minutes had only a 36% chance of
      survival. New measures, including use of the automatic external difibrillator, to
      reduce the "vertical" response are urgently needed.

PMID- 9596426
TI  - The effects of the Northridge earthquake on the pattern of emergency department
      care.
AB  - This study's objective was to describe the types of injuries that should be
      anticipated after a major earthquake. Data for the 6 days prior to the
      earthquake, the 6 days after the earthquake, and for the day of the earthquake
      the previous year were obtained from the Emergency Department of Northridge
      Hospital, Northridge, CA. Demographic data, including age and sex, as well as the
      reason for the visit, were obtained from patient logs. The average number of
      patients per day was 110 before the earthquake and 185 after the earthquake. On
      the day of the earthquake, 343 patients were seen. Lacerations increased from
      7.1% of all visits before the earthquake to 22.4% after the earthquake (P < .01).
      Immediately after the Northridge earthquake, there was a threefold increase in
      emergency patient visits. The biggest increase occurred in the number of patients
      presenting with contusions and lacerations. The number of pregnant women
      presenting in labor and with vaginal bleeding also increased. Disaster managers
      should take these patterns into account when planning for major seismic events.

PMID- 9596427
TI  - Implementing means restriction education in urban EDs.
AB  - This study evaluated the impact of a mail information campaign on emergency
      department (ED) professionals' knowledge about the lethal role of firearms in
      suicide, knowledge of appropriate strategies for warning caregivers of
      adolescents who have attempted suicide about firearms, and practices with respect
      to the delivery of such warnings. Responses obtained from physicians and nurses
      working in ED sites within the targeted city (Chicago) were compared with
      responses from ED professionals employed in a comparison city (Detroit). In
      Chicago, the percentage of respondents recommending firearm removal strategies
      increased from 60% at pretest to 76% at posttest. Individual reports of caregiver
      warnings per adolescent suicide exposure showed a significant decline in Chicago
      and a marginally significant decline in Detroit. Gains in knowledge about firearm
      warning strategies persisted in multivariate analyses controlling for subject
      demographic characteristics. The pattern of results suggests that the
      intervention may have effected changes in knowledge while having little impact on
      behavior. More intensive, interactive educational strategies may be needed to
      effect behavioral changes among ED professionals.

PMID- 9596428
TI  - A double-blind comparison between oral pseudoephedrine and topical oxymetazoline
      in the prevention of barotrauma during air travel.
AB  - To determine the efficacy of two decongestants (oral pseudoephedrine versus
      topical oxymetazoline) in the prevention of middle ear barotrauma during air
      travel, 150 adult volunteers with a history of ear pain during air travel were
      entered into a randomized, double-blind study conducted at two commercial
      airports. Each subject received 120 mg pseudoephedrine, oxymetazoline
      hydrochloride (0.05%), or a double placebo (capsule and nasal spray) administered
      30 minutes before flight departure. After arrival at their final destinations,
      volunteers were asked to complete a questionnaire and return it by mail to
      investigators. Questions included the intensity and duration of otologic symptoms
      experienced while flying and possible drug side effects. A total of 124 subjects
      completed the study; 41 received 120 mg of pseudoephedrine, 42 received
      oxymetazoline nasal spray, and 41 received a double placebo (capsule and nasal
      spray). The three treatment groups were similar with regard to age, sex, medical
      history, and flight profile. Symptoms of barotrauma were reported by 34% of those
      receiving pseudoephedrine versus 71% of the control group, for a relative risk
      reduction of 52% (95% confidence interval [CI] 33% to 71%). In contrast, 64% of
      the oxymetazoline group reported symptoms of barotrauma, for a relative risk
      reduction of 10% (95% CI, 3% to 17%). These results suggest that treatment with
      120 mg pseudoephedrine at least 30 minutes before flying appears to decrease the
      incidence of barotrauma. Oxymetazoline nasal spray is little more effective than
      placebo in reducing ear pain and discomfort associated with changing ambient
      pressures.

PMID- 9596429
TI  - Lyme carditis: a rare presentation in an unexpected setting.
AB  - A case is reported of a 27-year-old man who presented to an inner city trauma
      center after he had experienced several seizure-like episodes. He was diagnosed
      with Lyme carditis and required 6 weeks of treatment with intravenous ceftriaxone
      for complete resolution of his symptoms. The case is discussed along with a
      review of the literature.

PMID- 9596430
TI  - Acute thrombotic thrombocytopenic purpura presenting as expressive aphasia.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an uncommon and potentially fatal
      disease that is characterized by endothelial cell abnormalities, platelet
      dysfunction, microangiopathic hemolysis, fever, neurological abnormalities, and
      renal involvement. Before the introduction of plasmapharesis in the 1970s, TTP
      was fatal. This case report is presented to illustrate how subtly TTP can
      present, to discuss the updated criteria for TTP diagnosis, and to emphasize that
      with effective treatment now available, accurate and early diagnosis is essential
      to decrease morbidity and mortality.

PMID- 9596432
TI  - Endotracheal tube occlusion following blind oral intubation with the Endotrol
      (trigger) endotracheal tube: a case report.
AB  - Some cases of difficult airway intubation can be managed by using the Endotrol
      (trigger) endotracheal tube. This report describes such a case, in which the
      management of a difficult airway was facilitated initially by using the Endotrol
      tube; however, significant occlusion occurred approximately 16 hours later when
      the tube "kinked," leading to its partial collapse. The Endotrol tube has been
      used to maintain airways in critical and difficult situations, but its use for
      longer periods of intubation may need to be further studied.

PMID- 9596431
TI  - Nebulized glucagon in the treatment of bronchospasm in asthmatic patients.
AB  - This study sought to determine if nebulized glucagon, a well-known smooth muscle
      relaxant, is effective in relieving asthmatic bronchospasm. Ten subjects, aged 12
      to 26 years, with chronic stable asthma were studied in a pulmonary function
      laboratory under a randomized double-blind, placebo-controlled, crossover design.
      Bronchospasm was induced in each subject with progressive doses of nebulized
      methacholine until forced expiratory volume in 1 second (FEV1) had decreased at
      least 20% from baseline. Subjects then received either nebulized saline or 2 mg
      of nebulized glucagon. Spirometry was performed at 5, 15, and 30 minutes after
      treatment. Subjects then received 2.5 mg of nebulized albuterol and had
      spirometry 15 and 30 minutes thereafter. Each subject returned for testing with
      the alternative solution at least 1 week later. Treatment with nebulized glucagon
      resulted in a 58% +/- 15% improvement in FEV1 15 minutes after treatment compared
      with 36% +/- 7% after nebulized saline (P < .05). No adverse effects of glucagon
      treatment occurred. This study suggests that nebulized glucagon reduces
      methacholine-induced bronchospasm in asthmatic patients.

PMID- 9596433
TI  - Spontaneous rupture of an amyloid spleen in a patient on continuous ambulatory
      peritoneal dialysis.
AB  - An unusual case is reported of spontaneous rupture of the spleen in a 67-year-old
      woman suffering from end-stage renal disease secondary to amyloidosis. The
      splenic rupture is attributed to amyloid involvement of the spleen.

PMID- 9596434
TI  - Hypoglycemia presenting as acute respiratory failure in an infant.
AB  - Hypoglycemia, a common metabolic abnormality seen in the pediatric population, is
      most often easily diagnosed and rapidly treated with satisfactory outcome. If not
      recognized and treated in prompt fashion, however, hypoglycemia may cause
      irreversible central nervous system injury or expose the patient to unnecessary
      procedures; it rarely results in death. The classic emergency department (ED)
      presentation of hypoglycemia, the diabetes mellitus patient using hypoglycemic
      therapy, is frequently encountered and adequately managed with excellent outcome.
      Alternatively, the patient may present to the ED in a fashion suggestive of a
      situation other than hypoglycemia. For example, the patient with an altered
      sensorium following a traumatic event, with a focal neurologic finding, or with
      bradycardia--all situations in which hypoglycemia is the causative issue--may not
      be immediately recognized as such a metabolic problem. This report presents a
      case of a 9-month-old boy who presented with acute respiratory failure and mental
      status change; the initial ED impression was one of pneumonia with sepsis.
      Further evaluation uncovered the actual reason for the mental status change and
      respiratory insufficiency: hypoglycemia was noted on laboratory analysis; no
      clinical evidence of pneumonia was found after thorough ED evaluation and a
      prolonged hospital stay. His mental status improved and his respiratory
      insufficiency resolved after glucose therapy. No other explanation for the
      respiratory failure was found during the hospital admission. It is imperative
      that the emergency physician consider hypoglycemia in all patients with any
      degree of mental status abnormality, even when the findings seem to be explained
      initially by other etiologies.

PMID- 9596435
TI  - Shortness of breath secondary to a pet cockatiel.
AB  - A case of hypersensitivity pneumonitis in a 40-year-old patient secondary to a
      pet bird is presented. The clinical presentation, diagnosis, and management of
      hypersensitivity pneumonitis are reviewed.

PMID- 9596436
TI  - Effectiveness of mechanical versus manual chest compressions in out-of-hospital
      cardiac arrest resuscitation: a pilot study.
AB  - A prospective, randomized effectiveness trial was undertaken to compare
      mechanical versus manual chest compressions as measured by end-tidal CO2 (ETCO2)
      in out-of-hospital cardiac arrest patients receiving advanced cardiac life
      support (ACLS) resuscitation from a municipal third-service, emergency medical
      services (EMS) agency. The EMS agency responds to approximately 6,700 emergencies
      annually, 79 of which were cardiac arrests in 1994, the study year. Following
      endotracheal intubation, all cardiac arrest patients were placed on 100% oxygen
      via the ventilator circuit of the mechanical cardiopulmonary resuscitation (CPR)
      device. Patients were randomized to receive mechanical CPR (TCPR) or human/manual
      CPR (HCPR) based on an odd/even day basis, with TCPR being performed on odd days.
      ETCO2 readings were obtained 5 minutes after the initiation of either TCPR or
      HCPR and again at the initiation of patient transport to the hospital. All
      patients received standard ACLS pharmacotherapy during the monitoring interval
      with the exception of sodium bicarbonate. CPR was continued until the patient was
      delivered to the hospital emergency department. Age, call response interval,
      initial electrocardiogram (ECG) rhythm, scene time, ETCO2 measurements, and
      arrest outcome were identified for all patients. Twenty patients were entered
      into the study, with 10 in each treatment group. Three patients in the TCPR group
      were excluded. Measurements in the HCPR group revealed a decreasing ETCO2 during
      the resuscitation in 8 of 10 patients (80%) and an increasing ETCO2 in the
      remaining 2 patients. No decrease in ETCO2 was noted in the TCPR group, with 4 of
      7 patients (57%) actually showing an increased reading and 3 of 7 patients (43%)
      showing a constant ETCO2 reading. The differences in the ETCO2 measurements
      between TCPR and HCPR groups were statistically significant. Both groups were
      similar with regards to call response intervals, patient ages, scene times, and
      initial ECG rhythms. One patient in the TCPR group was admitted to the hospital
      but later died, leaving no survivors in the study. TCPR appears to be superior to
      standard HCPR as measured by ETCO2 in maintaining cardiac output during ACLS
      resuscitation of out-of-hospital cardiac arrest patients.

PMID- 9596437
TI  - A method for rapid intravenous infusion in shock resuscitation.
AB  - A technique for rapid intravenous infusion is described for patients in extremis.
      Using readily available materials, the saphenous vein at groin level is
      cannulated with an oversized catheter. Excellent flow rates are achieved.

PMID- 9596438
TI  - Myocardial infarction in children.

PMID- 9596439
TI  - Clinical predictors of mandibular fractures.
AB  - To evaluate the diagnostic accuracy of clinical signs and symptoms of mandibular
      fracture, a prospective study of emergency department patients presenting with
      mandibular trauma was undertaken. Patients with airway compromise, who were
      edentulous, or could not cooperate with the physical examination were excluded.
      Over a 1-year period, 119 patients were studied. The presence of malocclusion,
      trismus, facial asymmetry, or a positive result on the tongue blade test
      (inability to grasp and hold a tongue blade between the teeth) was significantly
      associated with a mandibular fracture. Malocclusion and facial asymmetry were
      strong predictors of fracture, and a negative result on the tongue blade test was
      a strong predictor of nonfracture.

PMID- 9596440
TI  - Spiral fracture of the humerus in a ball thrower.
AB  - Spiral fractures of the humerus in ball throwers are rare clinical entities that
      can be confused with pathologic fractures. These fractures have been reported in
      various throwing sports, arm wrestling, and hand grenade throwing. They most
      commonly occur in the distal third of the humerus in young, active individuals.
      They are often preceded by throwing arm pain. Neurologic sequelae are rare.
      Herein, a case is presented of spiral fracture of the humerus in a softball
      player, and the assessment and management of these fractures, as well as their
      etiologic contrast to stress and pathologic fractures, are reviewed.

PMID- 9596441
TI  - Stump appendicitis diagnosed preoperatively by computed tomography.

PMID- 9596442
TI  - Cases in electrocardiography.

PMID- 9596443
TI  - Prepare to be shocked: the evolving standard of care in treating sudden cardiac
      arrest.
AB  - Standards of care are devised by juries in courts of law. They "evolve," in part,
      according to public expectations as those expectations are honed by the
      profession in its literature, its forums, and as reported in the popular press
      and media. Sudden cardiac arrest is a major killer in the United States. A
      significant number of deaths from sudden cardiac arrest can be prevented by using
      automatic external defibrillators in the out-of-hospital setting. These devices
      have become cost effective, reliable, and readily available and the standard of
      care requiring their use in the out-of-hospital setting has arrived.

PMID- 9596444
TI  - The motorcyclist: easy rider or easy victim? An analysis of motorcycle accidents
      in Germany.
AB  - This report reviews the findings from 86 motorcycle accidents during a 1-year
      period at the Trauma Center "Bergmannsheil" in Bochum, Germany. A study of the
      case histories supplemented by telephone conversations yielded the following
      results: 90.7% of the patients were men, and the average age was 28.8 years; most
      of the accidents occurred in the 25- to 30-year-old age group (27.9%). Motorcycle
      accidents happened mostly during recreational rides on weekends in the
      summertime. Although there was a high rate of helmet use (98.8%), the head region
      was affected in 12 victims. Two patients died because of their severe head
      injuries (2.3%). Lower extremity injuries (46%), especially open tibia fractures
      (19.7%), were among the most common injuries sustained. Fractures of the distal
      radius constituted the largest portion of upper extremity injuries (18.8%). The
      average stay in our hospital was 35.4 days; 23.4% of the patients had to change
      jobs after the accident. Fifty percent of the crashes happened with motorcycles
      between 500 and 750 cc stroke volume. Although 34.5% possessed their driver's
      licenses for more than 8 years, they had not had much experience handling a
      motorbike. These results underline the fact that motorcycle accidents are
      sustained by young men in their working prime; as a result, these accidents pose
      a tremendous burden to individuals and society and every attempt should be made
      to offer highly qualified surgical and trauma care to minimize the damage to the
      motorbiker. A plea is made for more prevention measures like driver education,
      better road conditions, or legislative changes to prevent motorcycle crashes. The
      wearing of a helmet is strongly advocated.

PMID- 9596445
TI  - Evolving clinical practices and legal standards of care: softening the shock.

PMID- 9596446
TI  - Pain from urethral and intravenous catheterization.

PMID- 9596447
TI  - Rugby injuries.

PMID- 9596448
TI  - Generalized seizures caused by fluoxetine overdose.

PMID- 9596449
TI  - Manual removal of urinary bladder foreign body under ultrasound localization.

PMID- 9596450
TI  - Response to violence, mental health, and substance abuse in patients who are seen
      in primary care settings.

PMID- 9596452
TI  - Family practice applicant.

PMID- 9596451
TI  - The electronic house call.

PMID- 9596453
TI  - Socioeconomic influences on the transmission of human immunodeficiency virus
      infection: the hidden risk.
AB  - Worldwide, and in pockets of poverty in the United States, there is growing
      evidence that poverty is a major contributor to the spread of human
      immunodeficiency virus infection. Specific socioeconomic forces contributing to
      the spread of the infection include the status of women, prostitution, drug use
      in poor populations, the role of prisons, economic factors that disrupt families,
      and cultural attitudes. A lack of awareness of or an unwillingness to address the
      social, cultural, and economic forces contributing to the transmission of the
      human immunodeficiency virus have hampered attempts to stem the epidemic. A
      "social prevention" strategy is called for in which socioeconomic influences on
      human immunodeficiency virus transmission can be ameliorated. Practicing
      physicians should be aware of these forces because they profoundly influence the
      effectiveness of patient education, prevention, and treatment.

PMID- 9596454
TI  - Mifepristone (RU 486): current knowledge and future prospects.
AB  - Mifepristone (RU 486) has received recent attention for its effects as an
      abortifacient. Mifepristone has not yet been approved for use in the United
      States. The Food and Drug Administration issued an "approvable letter" in
      September 1996, but mifepristone will not be available in the United States until
      a new manufacturer is found. Experience with mifepristone is extensive in Europe,
      and there have been retrospective studies and large, controlled clinical trials
      of its efficacy. It is most efficacious when administered to women who are less
      than 8 weeks pregnant, in a single 600-mg oral dose followed 48 hours later by
      administration of intravaginal misoprostol. This regimen has a success rate of
      98%, as do most surgical abortive procedures. The most frequent adverse effect is
      painful contractions, which occur in up to 93% of women, with oral analgesia
      required in as many as half the cases. Large-scale surveys of women who elected
      medical abortion reported high patient satisfaction. Mifepristone is likely to
      have additional clinical uses. Researchers are exploring mifepristone's potential
      uses in cervical ripening and labor induction; contraception; delivery after
      intrauterine demise; treatment of breast cancer, unresectable meningioma, and
      prostate cancer; amelioration of endometriosis; and management of Cushing
      syndrome.

PMID- 9596455
TI  - Practitioner self-confidence and patient outcomes in acute low back pain.
AB  - OBJECTIVE: To compare outcomes for patients with acute low back pain who received
      care from practitioners with different self-confidence scores on a 4-item scale.
      DESIGN: Cross-sectional survey of practitioners. Prospective cohort study of
      patient outcomes. SETTING: Private practices and a group model health maintenance
      organization. PARTICIPANTS: One hundred eighty-nine practitioners, including
      private practice traditionally trained medical physicians, chiropractors, and
      physicians in a group model health maintenance organization, who were randomly
      chosen from practices across the state of North Carolina. These practitioners
      enrolled 1633 patients with acute low back pain into a prospective cohort study.
      METHODS: The practitioner survey contained 10 questionnaire items that measured
      aspects of practitioner confidence and attitudes in assessing and treating
      patients with low back pain. Patients were interviewed by telephone after the
      initial office visit and at 2, 4, 8, 12, and 24 weeks, or until complete
      recovery, whichever came first. RESULTS: Of 189 study practitioners, 95%
      responded to the survey. A 4-item scale, shown by factor analysis to describe
      practitioners' self-confidence, demonstrated good internal consistency among
      physicians and chiropractors. Chiropractors had significantly stronger self
      confidence scores than physicians. Among patients of primary care physicians and
      chiropractors, those who received care from practitioners with stronger self
      confidence scores did not differ in the time to functional improvement, overall
      patient satisfaction, or their perception of the completeness of care.
      CONCLUSION: The level of practitioner self-confidence, as measured by a 4-item
      scale, did not predict patient outcomes in the treatment of acute low back pain.

PMID- 9596456
TI  - Natural history of asymptomatic gallstones in family practice office practices.
AB  - BACKGROUND: Improved access to less invasive testing has resulted in more
      Americans being diagnosed with asymptomatic gallstones. The family physician has
      had to rely on community-based or referral patient studies to advise their office
      based patients about treatment options. OBJECTIVE: To understand the natural
      history of asymptomatic gallstones discovered through a routine patient care
      process in a rural, office-based research network of 9 family physician
      practices. PARTICIPANTS AND METHODS: Nine family physician practices agreed to
      comb their records for medical records of patients found to have asymptomatic
      gallstones during their routine primary care practice. Medical records were then
      reviewed annually for 5 years for evidence of gallstone-related problems Results
      were compared with previous English-language literature studies. RESULTS:
      Asymptomatic gallstones were found in 32 patients (19 women [59%] and 13 men
      [41%] with an average age of 59.5 years). Symptoms developed in 8 patients (25%)
      after an average latency period of 3 years 5 months. Seven patients underwent
      cholecystectomy; there was no gallstone-related mortality in this group. One
      patient who developed a ruptured gallbladder required an emergency procedure.
      CONCLUSIONS: Routine office practice is detecting only a small percentage of the
      asymptomatic gallstones expected by community-based screening studies. While more
      of these patients became symptomatic than in general population studies, most
      patients with asymptomatic gallstones required no treatment. Those patients in
      family practice offices who are serendipitously found to have gallstones can
      generally be followed up conservatively.

PMID- 9596457
TI  - Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the
      treatment of migraine.
AB  - OBJECTIVE: Sumatriptan hemisulfate nasal spray may provide a useful therapeutic
      option for patients with migraine who find injectable medications inconvenient or
      uncomfortable and for patients whose migraine-associated nausea and vomiting
      preclude the use of oral medication. This study was the first US trial to
      evaluate the effects of sumatriptan nasal spray administered for multiple
      migraine attacks. DESIGN/INTERVENTIONS: Sumatriptan nasal spray (5, 10, or 20 mg)
      was administered via a 1-shot nasal applicator into either nostril for up to 3
      migraine attacks occurring over 6 months in a randomized, double-blind, parallel
      group, placebo-controlled study. SETTING: Fifty-six outpatient clinical centers
      in the United States. PATIENTS: A total of 1086 men and women diagnosed with
      migraine with or without aura per International Headache Society criteria. MAIN
      OUTCOME MEASURES: Percentage of patients with headache relief (moderate or severe
      predose pain reduced to mild or none); percentage of patients with no or mild (vs
      moderate or severe) clinical disability; percentage of patients with nausea,
      vomiting, photophobia, or phonophobia; adverse events; clinical laboratory test
      results. RESULTS: Across attacks, headache relief in the 20-, 10-, and 5-mg drug
      and placebo groups was experienced 120 minutes postdose by 60%, 54%, 44%, and 32%
      of patients, respectively (P<.05 for each sumatriptan nasal spray group vs
      placebo, for the 10-mg vs 5-mg drug group, and for the 20-mg vs 5-mg drug group).
      Two thirds of the 20-mg patients treating 3 attacks experienced relief at 2 hours
      postdose for at least 2 of 3 attacks. Clinical disability scores at 120 minutes
      in the 20-, 10-, and 5-mg drug and placebo groups reflected no or mild impairment
      in 70%, 67%, 57%, and 50% of patients, respectively (P<.05 for the 10- or 20-mg
      drug group vs placebo group, and for the 20-mg vs 5- mg drug group). Similar
      efficacy rates were observed for nausea, photophobia, and phonophobia. For all
      parameters, individual-attack efficacy rates did not differ from across-attack
      rates. The incidence of adverse events was not dose related. The most frequently
      reported adverse event in the active treatment groups was taste disturbance (bad,
      bitter, or unpleasant). CONCLUSIONS: Sumatriptan hemisulfate nasal spray (5, 10,
      or 20 mg) is effective and well tolerated in the treatment of multiple migraine
      attacks. The 20-mg dose was associated with the highest efficacy rates across the
      greatest number of parameters.

PMID- 9596458
TI  - Family physicians' satisfaction with practice.
AB  - BACKGROUND: During the past decade, dramatic changes have occurred in the way
      family physicians deliver health care. OBJECTIVE: To examine how satisfied family
      physicians are with their practice and compensation and what factors are
      associated with higher or lower satisfaction. METHODS: As part of a larger study
      examining decision making for specific medical problems, a random sample of board
      certified family physicians were asked to rate on a 5-point Likert scale their
      satisfaction with practice, satisfaction with compensation, and likelihood that
      they would again select their current specialty. Responses were collapsed into
      those satisfied or highly satisfied vs those who were neutral or dissatisfied.
      The likelihood of again selecting family practice as a specialty was dichotomized
      similarly into those very likely or likely vs all others. Bivariate and multiple
      regression comparisons were made with demographic and practice characteristic
      variables. RESULTS: The overall response rate was 58.1% (N = 537). Most family
      physicians (82.4%) are satisfied with their careers, most (65.5%) are satisfied
      with the compensation they receive, and, if given the opportunity, most (74.9%)
      would again select family practice as their specialty. Factors that appeared to
      be associated with lower levels on more than 1 satisfaction measure included
      working in a group of physicians with 3 or fewer members and not including
      maternity care in one's practice. In addition, older physicians stated they were
      less likely to enter family practice again, and those who worked more hours were
      less satisfied with their compensation. CONCLUSIONS: Overall, family physicians
      are satisfied with their careers and compensation. The observation that those in
      smaller group practices were less satisfied suggests that practices with smaller
      numbers of members will continue to decline while the number of family physicians
      employed in larger group practices grows. This may have implications for health
      care delivery, especially in rural areas where smaller practices are more common.

PMID- 9596459
TI  - Variation in the diagnosis of upper respiratory tract infections and otitis media
      in an urgent medical care practice.
AB  - BACKGROUND: Variation among hospitalized medical conditions have been reported
      previously, but there is little information on variation among physicians for
      medical conditions that constitute a substantial part of ambulatory care.
      OBJECTIVE: To measure variation in the diagnosis of 2 common medical conditions,
      otitis media (OM) and upper respiratory tract infections (URIs) in an urgent care
      practice. DESIGN: Estimate the variation in the incidence of new diagnoses of OM
      and URIs among 19 physicians working at 2 urgent care clinics between January 1,
      1995, and March 31, 1995. Patients are seen in order of arrival, and assignment
      to each physician is random. PARTICIPANTS AND SETTING: Two urgent care clinics
      staffed by the same 19 physicians. During the 3-month study period, 21,259
      patients were seen at the 2 clinics; of these, 1839 (8.65%) received a diagnosis
      of first time OM; and 8020 (37.73%), of an URI. MAIN OUTCOME MEASURE: Incidence
      of new diagnoses of OM and URI estimated as a proportion of all diagnoses for
      each individual physician. RESULTS: There was substantial variation between
      physicians in the diagnosis of OM, ranging from a low of 4.2% to a high of 21.8%.
      There was less variation in the diagnosis of URI (31.7%-48.4%). Some physicians
      with a low incidence of OM or URI diagnoses had increased the proportion of
      diagnoses in the other diagnostic category. For OM the variation was greatest for
      children younger than age 5 years, but substantial variation was also found in
      adults. For URIs the variation was more uniform across all age groups. The
      variation was not explained by type of specialty training or years in medical
      practice. CONCLUSIONS: There is substantial variation between physicians in their
      diagnosis of OM and URI in an urgent care setting. This variation has
      implications for cost of diagnosing and treating these conditions, the training
      of physicians, and our understanding of the treatment of OM.

PMID- 9596460
TI  - Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective
      study and the risk of symptomatic diverticular disease in men.
AB  - OBJECTIVE: To examine prospectively the relationship between self-reported
      regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen
      and the risk of symptomatic diverticular disease. DESIGN: Prospective cohort
      study using a mailed baseline questionnaire in 1986, and follow-up every 2 years
      through 1992. SETTING: Male health professionals residing in 50 US states.
      PATIENTS: A total of 35 615 male health professionals (dentists, optometrists,
      veterinarians, physicians, pharmacists, osteopathic physicians, podiatrists) 40
      to 75 years of age at baseline and free of diagnosed diverticular disease, colon
      or rectal polyp, ulcerative colitis, and cancer prior to 1988. MAIN OUTCOME
      MEASURES: Follow-up questionnaires in 1988, 1990, and 1992 about use of NSAIDs,
      acetaminophen, and other variables including the diagnosis of symptomatic
      diverticular disease. RESULTS: During 4 years of follow-up, we documented 310
      newly diagnosed cases of symptomatic diverticular disease. After adjustment for
      age, physical activity, and energy-adjusted dietary fiber and total fat intake,
      regular and consistent use of NSAIDs and acetaminophen was positively associated
      with the overall risk of symptomatic diverticular disease (for users vs nonusers,
      relative risk [RR] for NSAIDs = 2.24, 95% confidence interval [CI], 1.28-3.91; RR
      for acetaminophen = 1.81, 95% CI, 0.79-4.11). Most of this positive association
      was attributable to cases associated with bleeding, particularly for
      acetaminophen (for users vs nonusers, RR for NSAIDs = 4.64, 95% CI, 0.99-21.74;
      RR for acetaminophen = 13.63, 95% CI, 3.53-52.60). CONCLUSIONS: These results
      suggest that regular and consistent use of NSAIDs in general and acetaminophen is
      associated with symptoms of severe diverticular disease, particularly bleeding.
      Further research is needed to investigate the potentially deleterious effect of
      NSAIDs and other medications on the lower gastrointestinal tract.

PMID- 9596461
TI  - Analgesics and symptomatic diverticular disease.

PMID- 9596463
TI  - The cost of medical dictation transcription at an academic family practice
      center.
AB  - BACKGROUND: Very little is known about the volume or cost of medical
      transcription in primary care. A study of the number of lines and cost of
      transcription at an academic family practice center was performed to establish
      the average number of lines and costs of transcription by level of service and
      type of provider (faculty physician, physician assistant, resident physician, and
      others). METHODS: Parallel 4-month sets of computerized billing records and
      computerized transcription summary logs (listing the patient name and
      identification, the dictator, the number of lines of dictation, and the date for
      each dictation) were merged and analyzed to compare the cost and volume of
      dictation by types of service and types of provider. RESULTS: During the study
      period there were 11,085 patient encounters, 9013 with transcription. The average
      cost of transcription per encounter using transcription was $3.96 and the median
      was $3.64. The cost per encounter ranged from $0.39 (3 lines of dictation) to
      $24.83 (191 lines of dictation). Faculty physicians and physician assistants had
      the lowest cost, resident physicians were intermediate in cost, and others (such
      as medical students) had the highest costs for medical transcription.
      Transcription costs rose with increasing level of service but became a smaller
      proportion of the collected fee, averaging only 5% for a level 5 encounter.
      CONCLUSIONS: The cost of transcription as a part of overhead was higher than
      anticipated. Specific education regarding dictation form and content and ways to
      decrease these costs is appropriate.

PMID- 9596462
TI  - Cigarette continuity programs and social support for smoking.
AB  - OBJECTIVE: To describe smokers' participation in cigarette continuity programs
      and the prevalence and structure of cooperative teams of smokers. METHODS: Cross
      sectional survey of smoking histories and continuity-program participation by
      individuals and their family members in a convenience sample of 176 current
      smokers at the University of Kentucky Chandler Medical Center, Lexington. Fisher
      exact test or chi2 tests were used to compare proportions. RESULTS: One of 3
      smokers collected coupons for a continuity program. Three quarters of the
      collectors redeemed their own coupons, and one quarter gave coupons to another
      collector. Coupon collectors reported an average team size of more than 2
      members. One fifth of collectors were teammates with another generation of family
      members, and one quarter of collectors aged 24 to 35 years were teammates with
      their children. Smokers were often aware of their relatives' coupon-collecting
      habits. CONCLUSIONS: Continuity programs have been a popular means of reinforcing
      smoking, especially within families and groups of friends. Continuity programs
      are novel in encouraging smoking and brand loyalty between generations.
      Continuity-program participants need to be aware of the risk of promoting smoking
      initiation by their children. Health advocates could use similar strategies to
      promote smoking cessation and prevention within families and other social groups.

PMID- 9596464
TI  - Treatment of depression in elderly patients: recent advances.
AB  - Although sometimes difficult to diagnose because of concurrent stressors, medical
      illness, or dementia, depression in elderly patients responds readily to
      appropriate therapy. When untreated, this disorder may result in increased
      morbidity and mortality or suicide. Effective therapeutic options for late-life
      depression, as in younger patients, include psychotherapy and pharmacotherapy.
      Short-term, highly focused forms of psychotherapy are helpful for elderly
      patients who are reluctant or unable to tolerate antidepressant medication.
      Because of their favorable adverse effect profiles and safety in cases of
      overdose, the selective serotonin reuptake inhibitors have, in most cases,
      replaced tricyclic antidepressants as first-line therapy when antidepressants are
      indicated. Psychostimulants may be helpful for medically ill elderly patients
      with depressive symptoms. Finally, electroconvulsive therapy offers a safe and
      effective alternative for patients refractory to or unable to tolerate
      antidepressant medication.

PMID- 9596465
TI  - Dictation in the presence of the patient.
AB  - We investigated the impact on patients' satisfaction and understanding of their
      condition and treatment recommendations when the care provider dictated the
      medical record in their presence. Providers' satisfaction and perceptions were
      also ascertained. Sixty patients were randomly placed into a treatment group
      where the provider dictated the medical record in their presence, and 60 patients
      were placed in a standard visit control group. Volunteer providers included
      residents, a faculty physician, and a physician assistant. A survey instrument
      completed with an interviewer measured patients' satisfaction with the provider,
      their care, the dictation technique, and their understanding of their diagnosis
      and treatment recommendations. The provider completed a similar questionnaire.
      Patients in both the dictation and control group were equally satisfied with
      their care, felt they understood what the provider told them about their medical
      conditions, and felt they understood their provider's recommendations. Within the
      dictation group, 44 (73%) liked the process, 24 (40%) believed they were helped
      to understand their condition, 22 (37%) believed they were helped in
      understanding recommendations, and 23 (38%) reported improved satisfaction with a
      visit that included dictation in their presence. In the dictation group, men felt
      more positive than women about dictation in their presence, including increased
      understanding of their condition and satisfaction with the visit. Patients aged
      56 years and older were also more positive about dictation in their presence,
      including improvement in their understanding of the provider's recommendations.
      Providers were equally satisfied with encounters using either method.

PMID- 9596466
TI  - Moderate leisure-time physical activity: who is meeting the public health
      recommendations? A national cross-sectional study.
AB  - We identified the prevalence of adults who met the 1993 Centers for Disease
      Control and Prevention and the American College of Sports Medicine moderate
      physical activity recommendation and the 1996 Surgeon General's Report on
      Physical Activity and Health energy expenditure guideline for leading a
      moderately active lifestyle. Participants were 16,890 women and 12,272 men at
      least 18 years old who were asked in the 1990 National Health Interview Survey
      about their leisure-time physical activities. About one third of US adults met
      either recommendation for moderate activity; 32% met the Centers for Disease
      Control and Prevention and the American Association of Sports Medicine
      recommendation and 38% met the surgeon general's guideline. Women, ethnic
      minorities, adults with lower educational attainment, and older adults were least
      active. Public health efforts are needed to address the issues related to
      physical inactivity and to provide organized programs to increase moderate
      physical activity levels in US adults.

PMID- 9596467
TI  - Cigarette smoking and the colorectal adenoma-carcinoma sequence: a hypothesis to
      explain the paradox.
AB  - As recognized precursor lesions to colorectal cancer, colorectal adenomatous
      polyps have been studied to enhance knowledge of colorectal cancer etiology.
      Although most of the known risk factors for colorectal cancer are also associated
      with the occurrence of colorectal adenomas, cigarette smoking has had a strong,
      consistent relationship with colorectal adenomas but is generally not associated
      with colorectal cancer. The explanation for this paradox is unknown. With data
      collected in 1986-1988 during a large case-control study based on colonoscopy
      results in New York City, New York, the authors investigated the possibility that
      the paradox may arise because subjects with colorectal adenomas were included in
      the control group of cancer case-control studies. The authors found a
      statistically significant increased risk between heavy cigarette smoking (smokers
      with > or = 40 pack-years of smoking) and risk of adenoma (odds ratio (OR) =
      1.61, 95% confidence interval (CI) 1.06-2.44). They saw no increased colorectal
      cancer risk from heavy cigarette smoking (OR = 1.02, 95% CI 0.52-1.99) using a
      "manufactured" control group to simulate a typical unscreened, population-based
      control group. When the authors compared these colorectal cancer cases with an
      adenoma-free control group examined by colonoscopy in a polytomous model with
      several case groups (newly diagnosed adenomas, carcinoma in situ, intramucosal
      carcinoma, and colorectal cancer), they found that the risk for 20-39 pack-years
      of smoking was elevated, although not statistically significant, and was similar
      for all four case groups. The risk for the highest smoking category (> or = 40
      pack-years) was more strongly elevated in all four case groups, although it was
      statistically significant for only the newly diagnosed adenoma and the carcinoma
      in situ cases (adenomas, OR = 1.59, 95% CI 1.05-2.42; carcinoma in situ, OR =
      2.05, 95% CI 1.01-4.15; intramucosal carcinoma, OR = 1.30, 95% CI 0.61-2.77; and
      colorectal cancer, OR = 1.30, 95% CI 0.64-2.65). While the authors' study is
      weakened by the lack of statistical significance concerning risk for colorectal
      cancer, these data offer some support for the hypothesis that the association
      between cigarette smoking and risk of colorectal cancer may have been masked by
      inclusion in the control group of subjects with adenomas. They also suggest that
      the major effect of smoking on the colorectal adenoma-carcinoma sequence occurs
      in the earlier stages of the formation of adenoma and the development of
      carcinoma in situ.

PMID- 9596468
TI  - Invited commentary: old problem, new wrinkles.

PMID- 9596469
TI  - Prevalence of renal stones in a population-based study with dietary calcium,
      oxalate, and medication exposures.
AB  - Little is known about the epidemiology of renal stones, in spite of the relative
      frequency of this painful condition. This population-based study examined
      reported renal stone diagnosis in 1,309 women aged 20-92 years to determine
      whether renal stones are associated with 1) food or water exposures or 2) lower
      bone mineral density and an increased likelihood of fractures. Results indicated
      a renal stone prevalence of 3.4%. The average age at diagnosis was 42 years.
      Renal stone formation was not associated with community of residence,
      hypertension, bone mineral density, fractures, high-oxalate food consumption, or
      ascorbic acid from food supplements. Women with renal stones consumed almost 250
      mg/day less dietary calcium (p < 0.01) than did women without stones and had a
      lower energy intake (p < 0.04). The authors' findings do not support the
      hypothesis that increased dietary calcium is associated with a greater prevalence
      of renal stones, nor do they identify renal stones as a risk factor for low bone
      mineral density. Furthermore, lack of other identifiable environmental correlates
      and the relatively young age at initial diagnosis suggest that genetic components
      of renal stone formation need further study.

PMID- 9596470
TI  - Association between self-reported leisure-time physical activity and measures of
      cardiorespiratory fitness in an elderly population.
AB  - Leisure-time physical activity enhances health and functioning in older
      populations. However, few data are available on the correlation between self
      reported leisure-time physical activity and cardiorespiratory fitness in the
      elderly. Treadmill exercise testing results were obtained for 1,006 members
      (median age 67 years) of a community-based sample. Subjects completed a
      standardized evaluation of medical/social history and measures of physical
      function. Leisure-time physical activity in the 12 months and 7 days before
      interview and over subjects' lifetimes was summarized as total and activity
      specific METs/week and [METs * (hours/week)]. Multiple linear regression was used
      to investigate the cross-sectional, sex-specific associations between peak oxygen
      consumption (VO2) and exercise duration. After adjustment for age, body mass
      index, smoking history, medical morbidity, direct measures of physical
      functioning, forced expiratory volumes, and maximum respiratory muscle pressure,
      leisure-time physical activity accounted for < or = 5% of the variance of VO2 and
      exercise duration. Results were unchanged when analyses were restricted to
      subjects who achieved high levels of exercise. These data indicate that measures
      of aerobic capacity cannot be used to "validate" self-reported leisure-time
      physical activity in older subjects, and they further suggest that beneficial
      effects of physical activity in the elderly are the result of metabolic effects
      that are not reflected well by maximal aerobic capacity during exercise testing.

PMID- 9596471
TI  - Exposure to environmental tobacco smoke and risk factors for heart disease among
      never smokers in the Third National Health and Nutrition Examination Survey.
AB  - The relative risk of coronary artery disease among never smokers exposed to
      environmental tobacco smoke (ETS) versus never smokers not exposed to ETS is
      approximately 1.2 based on more than a dozen epidemiologic studies. Most of these
      studies have controlled for the major heart disease risk factors, but residual or
      uncontrolled confounding remains a possible explanation for the epidemiologic
      findings. The authors studied 3,338 never-smoking adults aged 17 years or older,
      who are representative of all US never smokers, in the 1988-1991 Third National
      Health and Nutrition Examination Survey (NHANES III) to determine whether
      selected risk factors for heart disease differ between ETS-exposed and 
      nonexposed persons. Both self-reported ETS exposure (at home and at work) and
      serum cotinine levels were available, the latter reflecting recent ETS exposure.
      After adjustments were made for age, sex, race, and education among adults aged
      17 years or older, no significant differences were found between the ETS exposed
      and the nonexposed for any of 13 cardiovascular risk factors with the exception
      of dietary carotene, which was lower among the exposed. On the other hand,
      significant positive linear trends were found between serum cotinine and two risk
      factors (body mass index and alcohol consumption), and significant inverse trends
      were found with dietary carotene. There were also few differences between exposed
      and nonexposed never smokers among adults aged 40 years or older, who are most at
      risk of heart disease. In this group, however, there was an inverse linear trend
      between serum cotinine and high density lipoprotein cholesterol (p < 0.001). This
      finding could result from ETS exposure rather than be an indication of
      confounding; a similar inverse trend was found for children, confirming other
      results in the literature. Overall, these data suggest little potential for
      confounding by the heart disease risk factors studied here when ETS exposure is
      determined by self-report.

PMID- 9596472
TI  - Epidemiology of congenital cytomegalovirus infection: maternal risk factors and
      molecular analysis of cytomegalovirus strains.
AB  - To determine factors that influence the occurrence of congenital cytomegalovirus
      (CMV) infection, the authors surveyed prospectively 8,254 infants born in eastern
      Iowa between October 1989 and June 1994. The authors conducted a case-control
      study to identify maternal risk factors, matching each CMV-infected infant with
      three uninfected infants according to hospital and date of birth. CMV strains
      were compared by using the polymerase chain reaction (PCR) to identify common
      sources of infection. Of the 7,229 infants cultured successfully for CMV, 35
      (0.48%) were congenitally infected. Mothers of CMV-infected infants were more
      likely to be single (odds ratio (OR) = 3.05, p = 0.016), to work in sales (OR =
      4.93, p = 0.008), or to be students (OR = 5.01, p = 0.017). Conversely, women who
      worked in health-care professions were less likely to have a congenitally
      infected infant (OR = 0.14, p = 0.049). PCR analysis indicated 27 distinct
      strains of CMV, but two groups of infants (two infants per group) excreted
      strains with indistinguishable molecular patterns. One of these pairs of infants
      had older siblings who attended the same child-care center during their mothers'
      pregnancies. The authors concluded that demographic and occupational factors
      influenced the risk of giving birth to an infant with congenital CMV infection.
      Many distinct CMV strains were identified, suggesting that major point source
      outbreaks had not occurred. Nonetheless, point source acquisition of CMV from
      child-care environments did account for some cases of congenital CMV infection in
      eastern Iowa.

PMID- 9596473
TI  - Estimation of vaccine efficacy in the presence of waning: application to cholera
      vaccines.
AB  - The authors present a nonparametric method for estimating vaccine efficacy as a
      smooth function of time from vaccine trials. Use of the method requires a minimum
      of assumptions. Estimation is based on the smoothed case hazard rate ratio
      comparing the vaccinated with the unvaccinated. The estimation procedure allows
      investigators to assess time-varying changes in vaccine-induced protection, such
      as those produced by waning and boosting. The authors use the method to reanalyze
      data from a vaccine trial of two cholera vaccines in rural Bangladesh. This
      analysis reveals the differential protection and waning effects for the vaccines
      as a function of biotype and age.

PMID- 9596474
TI  - Sudden infant death syndrome: risk factor profiles for distinct subgroups.
AB  - The authors investigated risk profiles of sudden infant death syndrome (SIDS) as
      a function of age at death. A case-control study carried out in the Tyrol region
      of Austria enrolled 99 infants who died of SIDS between 1984 and 1994 and 136
      randomly selected controls. Early and late SIDS (< 120 days of age vs. > or = 120
      days) were defined according to the clear-cut bimodal age-at-death distribution.
      Inadequate antenatal care, low parental social and educational level, and the
      prone sleeping position were risk conditions that applied to both early and late
      SIDS. A marked seasonal variation (winter preponderance) was the most outstanding
      feature of late SIDS. A gestational age of < 37 weeks (odds ratio (OR) = 8.4, 95%
      confidence interval (CI) 2.6-26.0), repeated episodes of apnea (OR = 5.7, 95% CI
      1.2-27.0), low birth weight (< 2,500 g) (OR = 3.4, 95% CI 1.1-11.0), a family
      history of sudden infant death (OR = 2.9, 95% CI 1.1-7.5), and maternal smoking
      during pregnancy (OR = 2.2, 95% CI 1.0-4.5) were associated with early SIDS. This
      study identified two distinct subgroups of SIDS infants characterized by
      different risk conditions and ages at death. These results underline a multiple
      cause hypothesis for SIDS etiology which involves a genetic predisposition,
      immaturity in the first months of life, and environmental factors acting at
      various ages.

PMID- 9596476
TI  - Domestic pets as risk factors for alveolar hydatid disease in Austria.
AB  - To identify the risk of pet ownership (i.e., cats and dogs) for alveolar
      echinococcosis caused by Echinococcus multilocularis, the habits and activities
      of 21 patients (histologic confirmation or positive serology with corresponding
      evidence on an ultrasonogram, radiograph, or computed tomography scan) in Austria
      during the period 1967-1997 were compared with the habits and activities of 84
      controls matched by sex, age, and residence. Cat ownership (odds ratio (OR) =
      6.47, 95% confidence interval (CI) 1.54-27.29) and hunting (OR = 7.83, 95% CI
      1.16-52.77) were independent risk factors associated with alveolar hydatid
      disease. The study is not in agreement with the hypothesis that eating mushrooms
      or certain wild berries which grow near the ground are the main risk factors for
      acquiring this disease. No other behavior patterns or activities studied were
      identified as risk factors.

PMID- 9596475
TI  - Validity of self-reported diagnoses leading to hospitalization: a comparison of
      self-reports with hospital records in a prospective study of American adults.
AB  - The authors compared interview reports with hospitalization records of
      participants in a nationally representative survey to determine the accuracy of
      self-reports of ischemic heart disease, stroke, gallbladder disease, ulcers,
      cataract, hip fracture, colon polyps, and cancers of the colon, breast, prostate,
      and lung. The study cohort consisted of 10,523 participants from the First
      National Health and Nutrition Examination Survey in 1971-1975 who were aged 25-74
      years at the baseline examination and who completed a follow-up interview in 1982
      1984. Self-reports of hospitalization for breast cancer were confirmed as
      accurate for 100% of cases where a hospital record was available. Self-report
      accuracy was also high for ischemic heart disease (84%), cataract (83%), and hip
      fracture (81%); it was moderate for lung cancer (78%), prostate cancer (75%),
      gallbladder disease (74%), colon cancer (71%), and stroke (67%); but it was low
      for ulcers (54%) and colon polyps (32%). Some of the self-reports of ulcers
      (20%), hip fracture (9%), ischemic heart disease (7%), and stroke (7%) were found
      to reflect diagnoses of other conditions of anatomic proximity. Accuracy of self
      reports improved with higher levels of education, but was not generally related
      to age, gender, race, alcohol use, or smoking. The results suggest that self
      reports of some diseases can be taken as accurate, but self-reports of other
      conditions might require medical record verification in epidemiologic follow-up
      studies.

PMID- 9596477
TI  - Reliability and validity of three physical activity questionnaires in Flemish
      males.
AB  - The reliability and validity of three physical activity questionnaires were
      studied using 90 Flemish males (30 aged 30 years, 30 aged 35 years, and 30 aged
      40 years). Intraclass correlations (R) and kappa values were calculated to verify
      within judge and between judges reliability (objectivity) and test-retest
      reliability (stability) of the Tecumseh Community Health Study Questionnaire, the
      Five City Project Questionnaire, and the Baecke Questionnaire. Results showed
      high for within judge and between judges reliability. R coefficients for
      stability varied between 0.47 and 0.95. Kappa values varied between 0.20 and
      0.73. Concurrent validity was investigated by comparing three levels of
      professional status. Workmen had higher indices concerning physical activity
      during work than clerks and managers. Congruent validity, studied by means of
      principal-components analysis, confirmed subdivision of habitual physical
      activity into three entities, physical activity during work, sports activities,
      and general leisure time. These results indicate that reliable and valid data can
      be obtained in Flemish males by three interviewer-assisted physical activity
      questionnaires.

PMID- 9596478
TI  - Re: "Breast cancer, cigarette smoking, and passive smoking".

PMID- 9596479
TI  - Re: "Smoking and breast cancer: reconciling the epidemiologic evidence by
      accounting for passive smoking and/or genetic susceptibility".

PMID- 9596480
TI  - Re: "Relation of breast cancer with passive and active exposure to tobacco
      smoke".

PMID- 9596481
TI  - Tumor oxygenation correlates with molecular growth determinants in breast cancer.
AB  - Hypoxic tumor cells may represent a fraction of cells that are not susceptible to
      radiation or chemotherapy. Intratumoral oxygen partial pressure (pO2) is the
      result of oxygen delivery and consumption. Cell proliferation is one factor to
      effect oxygen consumption and we therefore studied the correlation between tumor
      pO2 and histological parameters. PATIENTS AND METHODS: In 36 women and one man
      (age range 29-80 years) with suspected breast cancer. Before tumor resection,
      intralesional pO2 was determined with a polarographic needle electrode. Under
      ultrasound control, 200 tumor measurements were obtained; Hb levels, Hk, arterial
      blood gas parameters, and tissue temperature were determined. The median of pO2
      values and the percentage of hypoxic areas (pO2 < 10 mmHg) were calculated and
      correlated with the histological type, grading, ER, PR, and the expression of Ki
      67, p53, EGFR, pS2, and c-erb-B2. RESULTS: The overall median pO2 was 44 mmHg,
      and 1024 measurements (13.8%) represented hypoxic areas. Ductal and lobular
      invasive cancers showed median pO2 of 41 mmHg. The mean pO2 of G1 tumors was 59
      mmHg and the hypoxic fraction 8%, in contrast to G2 tumors with 43 mmHg and 17%,
      and G3 tumors with 36 mmHg and 20.4% (p < 0.01). We observed a correlation with
      tumor size and an increased rate of hypoxic areas in T3-4 lesions (p < 0.02).
      Also tumors with negative nodes or positive ER had significantly higher pO2
      values, as did tumors with an overexpression of c-erb-B2, p53, and cathepsin D.
      CONCLUSION: Oxygenation of human breast cancers can safely be measured in
      patients prior to surgical therapy. pO2 values correlate both with prognostic
      markers examined histologically and with molecular growth factors. As the
      efficacy of preoperative or adjuvant treatment in individuals may depend on
      oxygen partial pressure, efforts to manipulate tumor pO2 for therapeutic purpose
      could be promising.

PMID- 9596482
TI  - Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer
      following preoperative chemotherapy.
AB  - Experimental laboratory data suggest that tumour growth is a balance between
      apoptosis and proliferation and that suppression of drug-induced apoptosis by
      oncogenes such as bcl-2 may be an important cause of intrinsic chemoresistance.
      The aims of this study were to assess the in vivo relationship of apoptosis to
      proliferation and Bcl-2 protein in human breast tumours both prior to
      chemotherapy and in the residual resistant cell population at the completion of
      treatment. We examined apoptotic index (AI), Ki67 and Bcl-2 protein expression in
      the tissue of 40 patients with operable breast cancer immediately before ECF
      preoperative chemotherapy, and in 20 of these patients with residual tumour, at
      the completion of treatment. There was a significant positive association between
      AI and Ki67 both before and after chemotherapy, and in their percentage change
      with treatment. In the residual specimens AI and Ki67 were significantly reduced
      compared with pre-treatment biopsies, while Bcl-2 expression showed a significant
      increase. No differences were seen in the pre-treatment levels of any of the
      variables measured between patients obtaining pathological complete response and
      those who did not, although numbers were small. These data suggest that apoptosis
      and proliferation are closely related in vivo. It is possible that the phenotype
      of reduced apoptosis and proliferation, and increased Bcl-2 may be associated
      with breast cancer cells resistant to cytotoxic chemotherapy, although this can
      only be proven by assessing larger numbers of patients in relation to
      pathological response.

PMID- 9596483
TI  - Differential effects of protein kinase C agonists on prostaglandin production and
      growth in human breast cancer cells.
AB  - A regulatory role for protein kinase C (PKC) and eicosanoids has been implicated
      in the control of breast cancer cell growth and function. Here we report on the
      effects of the two PKC agonists 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and
      bryostatin 1 on arachidonic acid metabolism, prostaglandin E2 (PGE2) production,
      and growth in MDA MB 231 human breast cancer cells. TPA caused a dose-dependent
      increase in PGE2 production which was maximal at 100 nM and which was blocked in
      the presence of an equimolar concentration of bryostatin 1. Bryostatin 1 alone
      had no effect on PGE2 synthesis. Both TPA and bryostatin 1 stimulated arachidonic
      acid release and reduced fatty acid incorporation into phosphatidylinositol,
      their combined effect being less than additive in co-incubation. Interleukin
      1beta (IL-1beta) induced a tenfold and twofold synergistic increase in PGE2
      production in the presence of TPA (10 nM) and bryostatin 1 (10 nM) respectively.
      Bryostatin 1 caused a dose-dependent inhibition of the phorbol ester-potentiated
      IL-1beta response. Treatment of MDA MB 231 cells for 4 days with TPA (10 nM) or
      bryostatin 1 (10 nM) inhibited cell growth by 74% and 20% respectively. Co
      treatment with both PKC agonists reversed the anti-proliferative effect of TPA to
      that seen with bryostatin 1 alone. In contrast the anti-proliferative action of
      ceramide, another PKC modulator, was unaffected in the presence of bryostatin 1.
      TPA also induced morphological changes in MDA MB 231 cells which were prevented
      by co-treatment with bryostatin 1. This study further supports a regulatory role
      for PKC in the control of eicosanoid synthesis and growth in human breast cancer
      cells. Although the findings are consistent with bryostatin 1 acting as an
      antagonist/weak agonist in relation to TPA action, the mechanistic basis for this
      differential action of TPA and bryostatin 1 is uncertain.

PMID- 9596484
TI  - Aneuploidy of chromosome 8 as detected by interphase fluorescence in situ
      hybridization is a recurrent finding in primary and metastatic breast cancer.
AB  - Previous work from our laboratory demonstrated aneuploidy for several chromosomes
      by interphase fluorescence in situ hybridization (FISH) in a high proportion of
      breast cancer specimens. In the literature, only limited data are available
      concerning chromosome 8 anomalies in breast cancer. To determine chromosome 8
      ploidy status in primary and metastatic specimens from 81 breast cancer patients,
      FISH analysis with a DNA probe recognizing chromosome 8 centromeres was
      performed. In all primary tumor specimens (n = 30), significant proportions of
      cells were aneuploid exhibiting gain of chromosome 8 copy numbers; in 75% of
      effusion specimens previously classified as malignant by cytology and/or FISH for
      various chromosomes (n = 40), cell populations aneuploid for chromosome 8 were
      detected; effusions previously classified non-malignant (n = 11) were diploid in
      10 cases, whereas one specimen contained rare hyperdiploid cells. Among these
      cells complex chromosomal aneuploidy could be demonstrated by two-color FISH,
      suggesting malignancy. Trisomic and tetrasomic clones were predominant in the
      majority of samples, but a marked intratumor cytogenetic heterogeneity was
      observed in most cases. Primary tumors and corresponding positive axillary lymph
      nodes revealed similar distributions of chromosome 8 copy numbers, analogous to
      previous findings with other chromosomes. This implies that, by using suitable
      FISH probes after examination of the respective primary tumor, an efficient
      search for (micro)metastasis might be feasible.

PMID- 9596486
TI  - Glycosphingolipid composition of MDA-MB-231 and MCF-7 human breast cancer cell
      lines.
AB  - Much evidence has shown that glycosphingolipids are involved in cellular
      recognition, regulation of cell growth, and metastasis. In the present study, the
      major glycosphingolipids of two widely studied human breast cancer cell lines
      were examined. The MCF-7 cell line has functional estrogen and EGF receptors, is
      dependent on estrogen and EGF for growth, and is uninvasive, while MDA-MB-231
      cells are a model for more aggressive, hormone-independent breast cancer. There
      was twice as much neutral glycolipid in MCF-7 cells as in MDA-MB-231 cells. The
      major neutral glycolipids in MDA-MB-231 cells were identified as CTH and
      globoside. MCF-7 cells also contained as the major neutral glycolipids CTH as
      well as globoside and two other glycolipids which were tentatively identified as
      galactosylgloboside and fucosylgalactosylgloboside by exoglycosidase treatments.
      Conversely, the ganglioside content was four fold higher in MDA-MB-231 cells
      compared to MCF-7 cells. The abundant gangliosides in both cell lines were GM3,
      GM2, GM1, and GD1a. A minor monosialoganglioside was detected in MDA-MB-231
      cells. The striking 18 fold greater amount of GM3 in MDA-MB-231 cells may have
      important implications because GM3 has been suggested to be involved in
      regulation of growth factor functions. In agreement, insertion of ganglioside GM3
      into the plasma membrane of MCF-7 cells blocked the growth stimulatory effect of
      EGF.

PMID- 9596485
TI  - Conjugation of interferon alpha to a humanized monoclonal antibody (HuBrE-3vl)
      enhances the selective localization and antitumor effects of interferon in breast
      cancer xenografts.
AB  - Human mammary carcinoma xenografts (MCF-7) growing in nude mice were treated with
      natural interferon alpha (n-IFN-alpha) alone or conjugated to a humanized
      monoclonal antibody (MoAb) anti-breast mucin (HuBrE-3vl) or to irrelevant human
      IgG1kappa. The IFN and the conjugates were administered as 20 intra-lesional
      (i.l.) injections to 1 of 2 xenografts in each mouse, or i.p. The growth
      inhibitory effects of HuBrE-3vl/nIFN-alpha were significantly greater than those
      of nIFN-alpha used as a single agent or conjugated to HuIgG1kappa. These effects
      occurred locally in the tumors receiving i.l. injections and systemically,
      although to a slightly lesser extent, in the noninjected tumors of mice treated
      i.l. and in the xenografts of mice treated i.p. Biodistribution studies showed
      that the uptake of 125I-HuBrE-3vl/nIFN-alpha by the tumors 24 hours after i.l. or
      s.c. injection was greater than that of 125I-HuIgG1kappa/nIFN-alpha, 125I-nIFN
      alpha alone, or by normal tissues, documenting a tumor targeting effect and
      favorable tumor:normal tissues (T:NT) ratios. The targeting effects and the
      resulting tumor growth inhibition were favored by the IFN-mediated up-regulation
      of the HuBrE-3vl reactive antigen, which was more prominent after 3 weeks of
      treatment with HuBrE-3vl/nIFN-alpha. These results were superior to those we
      obtained previously with nIFN-alpha conjugated to another MoAb of the same group
      (Mc5). These studies point out the potential usefulness of HuBrE-3vl/nIFN-alpha
      for the local and systemic treatment of breast cancer lesions by providing a
      means of delivering high doses of IFN to the tumors while minimizing the amount
      of IFN binding to normal tissues.

PMID- 9596487
TI  - Role of 99mTc-Sestamibi scintimammography by SPEM camera in the management of
      breast cancer in the elderly.
AB  - The incidence of breast cancer in the elderly is 10 fold higher than in the
      population younger than 65 years. Moreover, in this segment of the population
      there are not defined clear practice guidelines regarding patient management. X
      ray mammography, the most widely used diagnostic technique, is often inadequate
      to differentiate benign from malignant lesions. 99mTc Sestamibi scintimammography
      plays an important role as complement to mammography; in fact it is a very
      sensitive and specific method for breast cancer detection, when cancers > 1 cm
      diameter are considered. However, sensitivity values fall to 50-60% in the case
      of small tumors (T1a and T1b). In this study we present the results of a new
      Small Field Of View (SFOV) Gamma Camera with very high spatial resolution that
      allows the first Single Photon Emission Mammography (SPEM). Eighteen patients
      aged 71 +/- 6 years with mammographically detected breast lesions were submitted
      to a Prone Scinti Mammography (PSM) by conventional Gamma Camera and to a SPEM on
      craniocaudal view. A final diagnosis was reached by histopathology. SPEM
      correctly diagnosed 15 of 16 cancers, while PSM was not able to recognize 5
      malignant lesions with subcentimeter size. Both the techniques provided normal
      findings in the case of benign lesions. The 99mTc Sestamibi scintimammography,
      particularly when performed by SPEM camera, is a sensitive, specific, and non
      invasive method to define the nature of radiologically described breast masses
      and would be very useful as a complement to X-ray mammography in screening
      programs for breast cancer.

PMID- 9596488
TI  - Expression of leukemia inhibitory factor and its receptor in breast cancer: a
      potential autocrine and paracrine growth regulatory mechanism.
AB  - Leukemia inhibitory factor (LIF) is a pluripotent cytokine which has a diverse
      array of effects on hematopoietic and epithelial cells. Depending on the nature
      of the target cells, these effects can be growth-stimulatory or growth
      inhibitory. Receptors for leukemia inhibitory factor (LIFR) have been identified
      on a variety of hematopoietic and epithelial cells. We have recently demonstrated
      in vitro growth stimulation of human breast cancer cells, both primary tumors and
      cultured cell lines, by LIF. To begin to understand the in vivo relevance of
      these observations, we investigated the expression of LIF and LIFR in human
      breast cancer specimens. Specimens from 50 cases were immunostained with mouse
      monoclonal antibodies D62.3 and M1 (to stain for LIF and LIFR, respectively). LIF
      expression was observed in 78% of the specimens and correlated with favorable
      biological features, i.e. low S-phase fraction (SPF) (P = 0.001) and diploidy (P
      = 0.08). LIFR expression was observed in 80% of the tumors and correlated with
      the presence of estrogen receptor (ER) (P = 0.04) and diploidy (P = 0.07).
      Coexpression of LIF and LIFR was associated with diploidy (P = 0.02) and low SPF
      (P = 0.05). LIF staining was primarily cytoplasmic whereas LIFR staining was
      cytoplasmic in the majority of cases and membranous in a minority of cases. The
      presence of LIFR in the primary tumor specimens correlated with the growth
      stimulation of tumor cells (derived from the same specimens) by exogenous LIF in
      methylcellulose colony assays. The findings support a widespread but probably
      complex role for LIF and LIFR in breast tumor growth regulation which should be
      investigated in greater detail in larger cohorts of tumors.

PMID- 9596489
TI  - Epidermal growth factor in NMU-induced mammary tumors in rats.
AB  - In this work we analyze the hypothesis that tumors induced by i.p. N-nitroso-N
      methylurea injection express EGF-like peptides and EGF receptors which could be
      involved in the response to hormone manipulation. EGF receptors (EGFR) were
      determined in the purified membrane fraction of tumors from control and
      ovariectomized (OVX) animals and no significant differences were found in either
      maximal binding capacities (Q) or dissociation constants (Kd) between them.
      Neither did we observe differences between tumors that regressed (HR) or
      continued growing (HU) after ovariectomy. In order to test the ability of EGFR to
      trigger a biological response we measured the production of second messengers
      inositol triphosphates (IP3) and cAMP levels; we found that EGF increases IP3
      production in a dose-dependent way, while cAMP levels were not affected. In
      addition, EGF was able to induce in vitro cell proliferation in a concentration
      dependent manner when tested in primary cultures of tumor cells by the clonogenic
      soft agar technique. EGF/TGF-alpha activity was determined by a radioreceptor
      assay in tumor cytosols from control and OVX rats. Results showed a trend to
      lower values in tumors from OVX rats, but no differences between HR and HU
      tumors. A positive correlation was found between EGF/TGF-alpha activity and
      progesterone receptor maximal binding capacity. When we tested the action of
      estradiol and EGF added together to primary cultures of tumor cells we found an
      additive effect on cell proliferation. The study of steady state mRNA levels
      showed that E2 increases PgR and c-myc mRNA levels in HR but not in HU tumors. In
      conclusion, the autocrine loop EGFR-EGF/TGF-alpha present in all tumors is
      hormonally regulated, possibly by Pg, but is not related to the tumor response to
      ovariectomy.

PMID- 9596490
TI  - Cytogenetic evaluation of 20 sporadic breast cancer patients and their first
      degree relatives.
AB  - Many genetic abnormalities disclosed even in somatic cells like peripheral blood
      lymphocytes may mark footprint(s) of malignancy(ies). The present cytogenetic
      study on peripheral blood lymphocytes of sporadic breast cancer patients (n = 20)
      and their first degree relatives (n = 39) reports abnormalities of chromosomes
      16, 5, 12, and 17 respectively in 17.59%, 8.33%, 6.48%, and 5.57% cells of
      patients and 15.83%, 8.33%, 7.5%, and 5% cells of their first degree relatives.
      These common chromosomal abnormalities pave the way to assume why first degree
      relatives of sporadic breast cancer patients are at increased risk of developing
      the same or other malignancies.

PMID- 9596491
TI  - Complications of Baerveldt glaucoma drainage implants.
AB  - OBJECTIVES: To report the incidence and identify risk factors of postoperative
      complications after Baerveldt glaucoma drainage implantation. METHODS: A
      retrospective review of the medical records of all patients at the Bascom Palmer
      Eye Institute, Miami, Fla, who underwent placement of a Baerveldt glaucoma
      drainage implant from October 1, 1992, through October 31, 1996, to determine
      demographic characteristics, preoperative and postoperative intraocular
      pressures, and complications. Variables were analyzed using the Student t test
      and Fisher exact test to determine the association between delayed postoperative
      suprachoroidal hemorrhage and various potential risk factors. RESULTS: A total of
      107 eyes of 103 patients were identified. Suprachoroidal hemorrhage occurred in 4
      eyes (4%), with onset ranging from 3 to 33 days after implantation. Two eyes (2%)
      had choroidal effusions requiring surgical drainage, and 20 eyes (19%) had low
      choroidal effusions requiring only close observation. Tube blockage was observed
      in 5 eyes (5%). Four eyes (4%) had aqueous misdirection, 2 eyes (2%) had corneal
      decompensation, and 1 eye (1%) each had endophthalmitis, tube migration, corneal
      ulcer, hyphema, and implant migration. Patients who were older (P=.04) or had
      postoperative choroidal effusions (P=.03), low intraocular pressure immediately
      after the tube opened (P=.03), hypertension (P= .08), or atherosclerosis (P=.09)
      were more likely to develop suprachoroidal hemorrhage. CONCLUSIONS: A lower
      incidence of serious postoperative complications was observed in Baerveldt
      implantations in this study when compared with a recent report. Risk factors for
      serious complications were similar to trabeculectomy.

PMID- 9596492
TI  - Activated protein C resistance, factor V Leiden, and central retinal vein
      occlusion in young adults.
AB  - OBJECTIVE: To confirm the relationship between resistance to activated protein C
      (APC), factor V Leiden, and central retinal vein occlusion in young adults as
      reported in a recent study of patients younger than 50 years. PATIENTS AND
      METHODS: Patients younger than 50 years with central retinal vein occlusion were
      identified from the medical records of the Wills Eye Hospital Retina and Retina
      Vascular Services. Blood samples were taken from each patient and analyzed for
      resistance to APC and identification of factor V Leiden. RESULTS: Only 1 (4.7%)
      of 21 patients evidenced resistance to APC and the presence of factor V Leiden.
      This patient was also the only one to report a family history of thrombotic
      disease. CONCLUSIONS: We were unable to confirm the high percentage of resistance
      to ACP among young adult patients with central retinal vein occlusion. The
      finding of resistance to APC in only 1 (4.7%) of 21 patients is similar to that
      found in the general population.

PMID- 9596493
TI  - Plasma fibrinogen levels, other cardiovascular risk factors, and age-related
      maculopathy: the Blue Mountains Eye Study.
AB  - OBJECTIVE: To assess the relationship between stages of age-related maculopathy
      (ARM) and cardiovascular disease and cardiovascular disease risk factors,
      including serum lipid and plasma fibrinogen levels, smoking, cardiovascular
      events, systemic hypertension, diabetes mellitus, and obesity. DESIGN: A cross
      sectional study of 3654 subjects from a defined geographic area identified
      subjects with late age-related macular degeneration (ARMD) and early ARM from the
      masked grading of retinal photographs. The history, physical examination
      findings, and fasting blood samples provided data on possible risk factors.
      Logistic regression, adjusting for age, sex, and possible confounders, and 2-way
      analysis of variance were used to assess associations. RESULTS: The only factors
      significantly associated with ARM included the 2 established risk factors,
      smoking and family history of ARMD (odds ratios, 4.1 and 4.2, for late ARMD,
      respectively), and the 2 variables, body mass index (odds ratio, 1.78 for obese
      compared with normal body mass index for early ARM) and plasma fibrinogen level
      (odds ratio, 6.7 for a fibrinogen level of >4.5 g/L [highest quartile] compared
      with a fibrinogen level of <3.4 g/L [lowest quartile] for late ARMD).
      CONCLUSIONS: These findings support the concepts that associations exist between
      plasma fibrinogen levels and late ARMD, a body mass index outside the normal
      range, and early ARM, and between the family history and smoking and any ARM. We
      found no other significant associations with any history of cardiovascular
      disease or other risk factors for cardiovascular disease.

PMID- 9596494
TI  - Choriocapillaris degeneration and related pathologic changes in human diabetic
      eyes.
AB  - OBJECTIVES: To measure the extent of choriocapillaris degeneration (CCD) in
      diabetic choroids and to study the association of CCD with choroidal
      neovascularization and pathologic changes in Bruch's membrane-like basal laminar
      deposits. MATERIALS AND METHODS: Human choroids from 10 postmortem subjects
      (diabetic, 5 [group 1]; nondiabetic, 5 [group 2]) were incubated for the
      histochemical demonstration of alkaline phosphatase and nonspecific esterase
      activities, permitting analysis of the choroidal vasculature and
      polymorphonuclear leukocytes, respectively. The tissue was then flat embedded and
      sectioned for structural analysis. Areas of CCD were measured in the flat
      perspective by computer-assisted image analysis and verified in cross-sections of
      flat-embedded tissue. RESULTS: The CCD in choroids from subjects with diabetes
      (group 1) appeared in 2 patterns: diffuse (partial loss of alkaline phosphatase
      activity in a poorly defined area, ie, degeneration of some capillary segments)
      and focal (complete degeneration of choriocapillaris or loss of alkaline
      phosphatase activity in a relatively well-defined area). The mean+/-SD percentage
      of the choroid with focal CCD in group 1 was 5.08%+/-1.13% of the total choroidal
      area vs 1. 16%+/-0.35% in group 2 (P<.001). Focal CCD in group 1 was more
      prominent in the posterior pole than in the peripheral choroid. Choroidal
      neovascularization was associated with some areas of diffuse CCD in group 1.
      Pathologic changes in Bruch's membrane-like basal laminar deposits were often
      associated with CCD; the thickness of the deposits was greater in group 1 than in
      group 2 and greater in areas with focal CCD than in areas with diffuse or no CCD.
      CONCLUSION: The percentage of choroid with focal CCD in group 1 choroids was more
      than 4-fold greater than that in nondiabetic choroids. The presence of CCD was
      related to basal laminar deposits and, in some cases, to choroidal
      neovascularization.

PMID- 9596495
TI  - Antenatal dexamethasone and decreased severity of retinopathy of prematurity.
AB  - OBJECTIVE: To assess risk factors associated with the development of retinopathy
      of prematurity (ROP) in an urban population. DESIGN: Observational cohort study.
      SETTING: Bellevue Hospital Center, a regional perinatal referral center in New
      York City. PATIENTS: Surviving inborn infants with birth weight less than 1250 g
      undergoing an ophthalmologic screening examination. MAIN OUTCOME MEASURES:
      Screening examination results for ROP were obtained. Additional data included
      birth weight, gestational age, maternal factors, and common neonatal diagnoses
      and exposures. RESULTS: Sixty-three infants were included in the analysis. Mean
      +/- SD birth weight was 981+/-179 g and mean gestational age was 27.8+/-2.4
      weeks. Infants whose mothers received antenatal dexamethasone developed
      significantly less ROP that was stage 2 or higher than infants without a history
      of antenatal dexamethasone exposure--8.7% (2/23) vs 35% (14/40), respectively
      (P=.04). Birth weight, gestational age, respiratory distress syndrome,
      bronchopulmonary dysplasia, and patent ductus arteriosus were also significantly
      associated with the development of ROP that was stage 2 or higher. After
      controlling for these confounders by multiple logistic regression analysis,
      antenatal dexamethasone administration was associated with a significantly
      decreased risk of development of ROP stage 2 or higher (adjusted odds ratio [OR],
      0.14; 95% confidence interval [CI], 0.02-0.93). The association was stronger when
      the analysis was restricted to the 36 infants who were 24 to 28 weeks of
      gestational age (adjusted OR, 0.02; 95% CI, 0.00-0.76). CONCLUSION: Antenatal
      dexamethasone administration appears to be associated with a decreased incidence
      of development of ROP of stage 2 or higher in this urban population.

PMID- 9596496
TI  - Timing of initial screening examinations for retinopathy of prematurity.
AB  - OBJECTIVE: To test a screening protocol for retinopathy of prematurity (ROP) that
      uses the dual criteria of postconceptional age and chronological age, rather than
      a single parameter, to determine precisely when to begin eye examinations.
      METHODS: We retrospectively reviewed medical records of 179 infants (326 eyes)
      who had undergone laser treatment for threshold ROP. We entered their
      chronological and postconceptional ages at treatment into a database and
      evaluated various screening parameters to determine the combination of criteria
      that would allow us to safely postpone the initial eye examinations. RESULTS:
      Screening infants at 7 weeks of chronological age or 34 weeks of postconceptional
      age (whichever comes first), but not before 5 weeks of chronological age, seems
      to reliably detect the onset of threshold ROP while reducing the number of
      unnecessary early examinations. CONCLUSION: Simultaneously applied dual criteria
      of chronological age and postconceptional age may be a superior method of
      determining when to initiate ROP examinations and is preferable to using either
      chronological age or postconceptional age alone.

PMID- 9596497
TI  - Malignant epithelial tumors of the lacrimal gland: a clinicopathologic study of
      21 cases.
AB  - OBJECTIVE: To analyze 120 lacrimal gland masses collected during a 23-year period
      in the Ophthalmic Pathology Laboratory at the Cullen Eye Institute, Houston, Tex.
      METHODS: Of the 120 lacrimal gland tumors, we focused on a detailed
      clinicopathologic study of 21 malignant epithelial tumors. Follow-up was
      available in 19 (90%) of 21 cases. RESULTS: About two thirds of the masses (75
      cases) were inflammatory, one third (41 cases) were of epithelial origin, and 3%
      (4 cases) were malignant lymphomas. Of the epithelial tumors, 17 (41%) were
      benign mixed tumors, 12 (29%) were adenoid cystic carcinomas arising de novo, 2
      (5%) were adenocarcinoma arising de novo, 7 (17%) were malignant mixed tumors,
      and 3 (7%) were metastatic carcinoma. All of the patients with adenoid cystic
      carcinoma had local recurrences, and 60% of the patients died of their tumors
      (mean survival, 5 years); only 2 patients were alive 13 and 16 years after the
      initial surgery, both of whom had radical surgical procedures for recurrence
      following orbital exenteration. CONCLUSION: The histopathologic classification
      and management of these tumors are discussed. This study supports the dismal
      prognosis of adenoid cystic carcinoma arising de novo.

PMID- 9596498
TI  - Screening of myopic photorefractive keratectomy in eye bank eyes by computerized
      videokeratography.
AB  - BACKGROUND: In contrast to incisional keratotomy, corneas that have undergone
      photorefractive keratectomy may be difficult to detect by inspection with
      slitlamp biomicroscopy alone. Eye bank corneas that have undergone high myopic
      refractive surgical correction could potentially result in substantial
      postoperative hyperopic correction if used as donor tissue for corneal
      transplantation. Surface irregularities or displacement of the treated optical
      zone within the graft in relation to the entrance pupil of the recipient could
      result in significant induced astigmatism and distortion. This study examines
      computerized videokeratographic screening of eye bank globes as a strategy for
      detecting myopic photorefractive keratectomy. METHODS: Preoperative and
      postoperative corneal topographic maps of freshly enucleated human and rabbit
      eyes that have undergone myopic photorefractive keratectomy with an excimer laser
      were placed in a globe-fixating device and analyzed using a vertically oriented
      videokeratoscope. The same system was applied in an actual eye bank setting, and
      potentially transplantable globes from donors without a history of corneal
      surgery were analyzed. RESULTS: Computerized videokeratography using a vertically
      mounted system reliably detected photorefractive keratectomy in 12 of 12 human
      eye bank corneas treated by excimer photorefractive keratectomy in a range
      between -1.5 to -6.0 diopters. This method also detected similar changes on lased
      rabbit corneas enucleated 6 weeks after excimer surgery. Data processed with the
      tangential mode yielded a "bull's-eye" topography pattern reflecting central
      corneal flattening that was more sensitive in detecting myopic corrections than
      the conventional axial formula-based color maps. False-positive results were not
      detected in 96 cadaver globes sequentially screened in the eye bank. CONCLUSIONS:
      Computerized videokeratography represents a feasible method to screen donor
      globes for myopic photorefractive keratectomy as shown by the in vitro and rabbit
      models. However, only whole globes and not corneoscleral sections are amenable to
      processing with this technique. Tangential maps provided greater sensitivity in
      detecting low myopic corrections than the axial formula-based color maps.

PMID- 9596499
TI  - Storage of human corneas in dextran and chondroitin sulfate-based corneal storage
      medium: changes in stromal free sodium.
AB  - OBJECTIVES: To evaluate the hydration and the levels of free and total sodium in
      human corneal stromata preserved for up to 21 days in a dextran and chondroitin
      sulfate-based corneal storage medium (Optisol-GS, Chiron IntraOptics, Irvine,
      Calif) and to evaluate the effect of epithelial removal on stromal sodium and
      hydration parameters. METHODS: Stromal hydration was evaluated
      thermogravimetrically. A sodium-specific electrode and an atomic absorption
      spectrophotometer were used to determine the amounts of free and of total stromal
      sodium, respectively, of preserved human corneas. In 50% of the corneas, the
      epithelium was removed prior to placement in the storage medium. After 3, 7, 14,
      or 21 days at 4 degrees C, corneas were removed from the storage medium and
      sodium measurements were taken. RESULTS: In corneas with an intact epithelium,
      the stromal hydration as well as the stromal free sodium and total sodium levels
      were relatively constant up to 21 days of storage in the preservation medium. In
      the absence of the epithelium, the water and sodium contents of the stroma
      increased significantly during storage. CONCLUSION: The presence of an intact
      epithelium is required for maintaining the hydration and sodium levels within the
      corneal stroma during storage. Removal of the epithelium prior to storage results
      in increased sodium values and hydration, which may affect postkeratoplasty
      deturgescence.

PMID- 9596500
TI  - H-7 disrupts the actin cytoskeleton and increases outflow facility.
AB  - OBJECTIVES: To determine the effects of the serine-threonine kinase inhibitor H-7
      on (1) cell junctions and the attached actin-based cytoskeleton in cultured
      bovine aortic endothelial cells, and (2) outflow facility in living monkeys.
      METHODS: Bovine aortic endothelial cells were cultured by standard techniques.
      The architecture and distribution of actin filaments, vinculin, and beta-catenin
      in bovine aortic endothelial cells were studied by immunolabeling before and
      after exposure to H-7 at various concentrations and durations. Outflow facility
      (perfusion) and intraocular pressure (Goldmann tonometer) were determined before
      and after the intracameral or topical administration of H-7 or a vehicle.
      RESULTS: In bovine aortic endothelial cells, exposure to H-7 produced a
      reversible time- and concentration-dependent disruption of actin microfilaments
      and an alteration in the organization of cell-cell and cell-matrix adhesions. In
      monkeys, intracameral and topical administration of H-7 dose dependently and
      reversibly doubled facility, and topical H-7 reduced intraocular pressures.
      CONCLUSION: H-7 increases outflow facility in monkeys, probably by inhibiting
      cell contractility, cytoskeletal support, and cell-cell adhesions in the
      trabecular meshwork.

PMID- 9596501
TI  - Choroidal nevi in a white population: the Blue Mountains Eye Study.
AB  - OBJECTIVE: To determine the prevalence, morphologic characteristics,
      associations, and frequency of features reported to predict growth of choroidal
      nevi in a large population-based sample. METHODS: A total of 3654 subjects aged
      49 to 97 years participating in the Blue Mountains Eye Study had a detailed eye
      examination, including photography of 6 standard retinal fields. Nevi were graded
      from photographs. RESULTS: Nevi were present in 6.5% of the population (n = 232),
      and were distributed equally between eyes. There was a slight decrease in nevus
      prevalence with increasing age. Nevus prevalence was higher in women than men,
      but this difference was not statistically significant. The mean nevus diameter
      was 1.25 mm (SD, 0.72 mm; range, 0.5 to >4.5 mm). Eighty-seven percent of nevi
      were blue gray and 6% had a hypomelanotic or amelanotic appearance. There were no
      significant associations between nevi and iris or skin color or sun-induced skin
      damage, but nevi were significantly less frequent in persons with blond hair. No
      nevus associations were found with visual impairment, cataract, or glaucoma.
      Clearly visible drusen were seen on 42% of nevi and were larger and more
      centrally distributed as nevus size increased. Features previously identified as
      predicting nevus growth, such as serous elevation and orange or other pigment,
      were seen rarely. CONCLUSION: Choroidal nevi in the general population are
      frequent, small, have few features that are commonly reported to indicate
      potential for growth, and rarely affect visual acuity.

PMID- 9596502
TI  - Age-specific prevalence and causes of blindness and visual impairment in an older
      population: the Rotterdam Study.
AB  - OBJECTIVE: To study the prevalence and causes of blindness and visual impairment
      in various age categories of a large population-based study. METHODS: For the
      study, 6775 subjects aged 55 years or older underwent an extensive ophthalmologic
      screening examination, including measurements of visual acuity and the visual
      field and fundus photography. The causes of blindness or visual impairment were
      determined using all screening information and medical records. RESULTS: The
      prevalence of blindness, according to World Health Organization criteria, ranged
      from 0.1% in subjects aged 55 to 64 years to 3.9% in subjects aged 85 years or
      older; the prevalence of visual impairment ranged from 0.1% to 11.8%. For persons
      younger than 75 years, myopic degeneration and optic neuropathy were the most
      important causes of impaired vision. For persons aged 75 years or older, age
      related macular degeneration was the major cause of the increased prevalence of
      blindness, whereas age-related cataract predominantly caused the increased
      prevalence of visual impairment. CONCLUSIONS: The hierarchy of causes of
      blindness and visual impairment is highly determined by age. As yet, little can
      be done to reduce the exponential increase of blindness; however, adequate
      implementation of surgery to treat cataract could reduce visual impairment by one
      third. Underuse of ophthalmologic care is a prominent cause of the high frequency
      of untreated cataracts among the elderly.

PMID- 9596503
TI  - Case-control designs for clinical research in ophthalmology.

PMID- 9596504
TI  - Test of divided visual attention predicts automobile crashes among older adults.

PMID- 9596505
TI  - Should laser refractive surgery be delayed? The benefits in deferring laser
      refractive surgery outweigh the disadvantages.

PMID- 9596506
TI  - There is no benefit to deferring laser refractive surgery.

PMID- 9596507
TI  - Intraocular coccidioidomycosis diagnosed by skin biopsy.
AB  - OBJECTIVE: To describe ocular findings in 2 patients with disseminated
      coccidioidomycosis diagnosed by skin biopsy. METHODS: The clinical and
      histopathologic findings of the 2 patients were reviewed retrospectively.
      RESULTS: One patient had a unilateral, granulomatous iridocyclitis with multiple
      iris nodules and a large vascularized anterior chamber mass, in the setting of
      pulmonary, cutaneous, and skeletal infection by Coccidioides immitis. The second
      patient developed papilledema and multifocal chorioretinitis accompanied by
      pulmonary, cutaneous, and meningeal C immitis infection. In each case,
      examination of the skin biopsy specimen revealed C immitis spherules. Treatments
      included local and systemic amphotericin B and oral fluconazole. CONCLUSIONS:
      Although rare, intraocular involvement can occur in the setting of disseminated
      coccidioidomycosis. A thorough systemic evaluation and biopsy of suspicious skin
      lesions can aid in the diagnosis.

PMID- 9596508
TI  - Reversal of siderosis.

PMID- 9596509
TI  - Adverse effects of latanoprost on patients with medically resistant glaucoma.

PMID- 9596510
TI  - Cystoid macular edema associated with latanoprost use.

PMID- 9596511
TI  - Persistence of fetal vasculature in the eyes of patients with incontinentia
      pigment.

PMID- 9596512
TI  - Palpebral myiasis causing preseptal cellulitis.

PMID- 9596513
TI  - Implantation of glaucoma drainage implant tube into the ciliary sulcus in
      patients with corneal transplants.
AB  - The placement of glaucoma drainage implants may be complicated by tube-corneal
      touch and endothelial decompensation, particularly after corneal transplantation.
      We describe an innovative surgical approach to glaucoma drainage implant
      procedures that may decrease such complications. The approach involves placement
      of the shunt tube into the ciliary sulcus. This approach may serve as an
      alternative to anterior chamber angle or pars plana implant placement in
      pseudophakic or aphakic eyes with refractory glaucoma and a high risk for corneal
      decompensation.

PMID- 9596514
TI  - Paranasal sinus endoscopy and orbital fracture repair.
AB  - Although excellent results may be achieved in the management of many orbital
      floor injuries with standard transconjunctival or transcutaneous approaches,
      visualization of the posterior edge of the orbital floor or medial wall defect
      may be challenging at times. We describe our experience using endoscopic
      examination of the orbital floor through maxillary sinus approaches during the
      repair of selected orbital floor fractures. Owing to the posterosuperior
      angulation of the orbital floor, these approaches allow better visualization of
      the posterior edge of fractures involving the posterior portion of the orbital
      floor than do the standard transconjunctival approaches, and they facilitate
      confirmation that all orbital soft tissues have been elevated from the fracture
      site. We have used these techniques successfully in 9 patients with fractures
      involving either the posterior portion of the orbital floor or the medial wall or
      both.

PMID- 9596515
TI  - Metastatic gastric carcinoma to the optic nerve.

PMID- 9596516
TI  - Choroidal melanoma and neurofibromatosis type 1.

PMID- 9596517
TI  - Syphilitic uveitis and dermatitis.

PMID- 9596518
TI  - Capitated care.

PMID- 9596519
TI  - Capitated care.

PMID- 9596520
TI  - Corneal thickness and applanation pressure.

PMID- 9596521
TI  - Botulinum toxin therapy for essential infantile esotropia in children.

PMID- 9596522
TI  - Generic prednisolone suspension substitution.

PMID- 9596523
TI  - Two olfactory marker proteins in Xenopus laevis.
AB  - Mature olfactory receptor neurons of mammals are characterized by the expression
      of the highly conserved olfactory marker protein (OMP) encoded by single copy
      genes. In Xenopus laevis, two homologous genes encoding olfactory marker proteins
      have been identified that share a sequence identity with mammalian OMPs of about
      50%. Sequence comparison revealed significant variability in the N-terminus and C
      terminus regions; in contrast, two internal domains were highly conserved between
      amphibian and mammalian OMPs, suggesting some functional relevance. The two OMP
      subtypes were regionally expressed in the olfactory nasal epithelium of Xenopus.
      XOMP1 transcripts were more abundant in the lateral diverticulum and XOMP2 in the
      medial diverticulum. The lateral location of XOMP1 and medial location of XOMP2
      correspond to the suggested locations of olfactory receptor neurons responsive to
      water-borne and air-borne odorants, respectively.

PMID- 9596524
TI  - Corticocortical communication via the thalamus: ultrastructural studies of
      corticothalamic projections from area 17 to the lateral posterior nucleus of the
      cat and inferior pulvinar nucleus of the owl monkey.
AB  - Electron microscopic anterograde autoradiography has been used to analyze the
      morphology and postsynaptic relationships of area 17 cortical terminals in the
      lateral division of the lateral posterior nucleus (LPl) of the cat and medial
      division of the inferior pulvinar nucleus (IPm) of the owl monkey. Such terminals
      are thought to arise exclusively from layer 5 in the cat and primate (Lund et al.
      [1975] J. Comp. Neurol. 164:287-304; Abramson and Chalupa [1985] Neuroscience
      15:81-95). All labeled terminals in both nuclei exhibited the morphology of
      ascending "lemniscal" afferents. That is, they contained round vesicles, were
      large, made asymmetrical synaptic and filamentous nonsynaptic contacts, and were
      classified as RLs. These cortical RLs also exhibited the postsynaptic
      relationships of lemniscal afferents. Thus, they were presynaptic to large
      dendrites within glial encapsulated glomeruli, where a majority was involved in
      complex synaptic arrangements called triads. They also were found adjacent to
      terminal profiles with pleomorphic vesicles but never adjacent to small terminals
      containing round vesicles. Our results suggest that the layer 5 projection from
      area 17 provides a functional "drive" for some LPl and IPm neurons. Information
      carried over this "re-entrant" pathway (Guillery [1995] J. Anat. 187:583-592)
      could be modified within the LPl and IPm by both cortical and subcortical
      pathways and subsequently conveyed to higher visual cortical areas, where it
      could be integrated with messages carried through the well-documented
      corticocortical pathways (Casagrande and Kaas [1994] Cerebral cortex New York:
      Plenum Press).

PMID- 9596525
TI  - Early region-specific gene expression during tract formation in the embryonic rat
      forebrain.
AB  - Expression profiles of two recently isolated cDNA fragments, M1 and M2, expressed
      in the medial telencephalon, were analyzed in developing rat forebrain by in situ
      hybridization histochemistry and correlative immunocytochemistry. M1 expression
      was observed in the most ventral portion of the hippocampal rudiment with a sharp
      dorsal boundary, from embryonic day (E) 12 onward. Its location corresponded to
      the fimbrial anlage. As the fimbria developed, segregated expression of M1 and
      neuron-specific class III beta-tubulin or GAP-43 became apparent, suggesting that
      part of the neuroepithelium producing fimbrial neuroglia expresses M1. M2
      expression in the E12 telencephalon was confined to part of the medial cerebral
      wall, including the presumptive preoptic region and hippocampus, with a diffuse
      dorsal boundary. At the same stage, M2 expression also occurred in part of the
      dorsal diencephalon adjacent to the M2-positive telencephalic region, with caudal
      extension along the dorsal midline, and in the zona limitans intrathalamica. M2
      expression domains lacked neuron-specific class III beta-tubulin
      immunoreactivity. During later stages, M2 expression was found in association
      with the corpus callosum, hippocampal commissure, fimbria, optic nerve, stria
      medullaris, tract of the zona limitans, and habenulopeduncular tract. In most
      cases, M2 expression was detected in regions corresponding to fiber tracts prior
      to arrival of the earliest axons, which could be detected by TAG-1- or GAP-43
      immunohistochemistry. These findings suggest that specialized cell populations
      express M1 and/or M2 genes in paramedian regions of the forebrain in advance of
      developing axonal pathways and may be involved in early specification of tract
      location and differentiation of tract neuroglia.

PMID- 9596526
TI  - Hippocampal alpha2a-adrenergic receptors are located predominantly
      presynaptically but are also found postsynaptically and in selective astrocytes.
AB  - Alpha-adrenergic receptor, subtype 2A (alpha2A-AR), activation is one of the
      primary modes of action for norepinephrine (NE) in the rat hippocampal formation.
      In this study, alpha2A-AR immunoreactivity (alpha2A-AR-I) was localized by light
      and electron microscopy in the rat hippocampus and dentate gyrus by using a
      previously characterized antibody to the rat alpha2A-AR. By light microscopy,
      dense alpha2A-AR-I was observed in the pyramidal and granule cell layers. Diffuse
      and slightly granular alpha2A-AR-I was found in the neuropil in all other
      laminae, notably stratum lacunosum-moleculare. Ultrastructurally, alpha2A-AR-I
      was found in neuronal cytoplasm associated with large multivesicular-like
      organelles and with clusters adjacent to endoplasmic reticula and/or plasmalemma.
      The distribution of alpha2A-AR-I in the strata oriens, radiatum, and lacunosum
      moleculare of hippocampal CA1 and CA3 regions and in the molecular layer of the
      dentate gyrus was remarkably similar (n > 2,000 profiles examined): alpha2A-AR-I
      was found in axons and terminals (approximately 40%), glia (approximately 30%),
      dendritic spines (approximately 25%), and dendritic shafts (approximately 5%).
      This mixed pre- and postsynaptic distribution was not seen in the stratum lucidum
      of the CA3 region and the dentate hilar region, where most alpha2A-AR-I was found
      in axons (approximately 60%) and glia (approximately 30%). Alpha-2A-AR-labeled
      axons were small and unmyelinated; labeled terminals usually formed asymmetric
      synapses on unlabeled spines; and labeled dendritic spines were morphologically
      similar to pyramidal or granule cells. Dual labeling studies demonstrated that
      some axons contained alpha2A-AR-I and tyrosine hydroxylase (TH), the
      catecholaminergic synthesizing enzyme, and that some TH-labeled terminals were in
      close proximity to alpha2A-AR-labeled spines and glia. These studies demonstrate
      that hippocampal alpha2A-AR-I is localized (1) presynaptically in both
      noncatecholaminergic and catecholaminergic terminals, (2) postsynaptically in the
      dendritic spines of pyramidal and granule cells near catecholaminergic terminals,
      and (3) in some glial processes. These results suggest several sites for NE to
      exert its effects on hippocampal alpha2A-ARs.

PMID- 9596527
TI  - In situ hybridization analysis of leucomyosuppressin mRNA expression in the
      cockroach, Diploptera punctata.
AB  - In the cockroach Diploptera punctata, sequencing of the cDNA for the insect
      myoinhibitory neuropeptide, leucomyosuppressin (LMS), has demonstrated that LMS
      is the only Phe-Met-Arg-Phe-amide (NH2) (FMRFamide)-related peptide to be encoded
      by this gene (Donly et al. [1996] Insect Biochem. Mol. Biol. 26:627-637).
      However, in the present study, high performance liquid chromatography analysis of
      brain extracts showed six discrete FMRFamide-like immunoreactive fractions, one
      of which co-eluted with LMS. This study compared the distribution of FMRFamide
      related peptides visualized by immunohistochemistry with LMS mRNA expression
      demonstrated by in situ hybridization in D. punctata. Immunohistochemistry with a
      polyclonal antiserum generated against FMRFamide, but which recognizes extended
      RFamide peptides, demonstrated numerous RFamide-like immunoreactive cells and
      processes in both nervous and nonnervous tissues. RFamide-like immunoreactivity
      was found in cells and processes of the brain and optic lobes, the stomatogastric
      nervous system, including the frontal and ingluvial ganglia, and the
      suboesophageal ganglion. Immunoreactivity was also present in all ganglia of the
      ventral nerve cord and in the alimentary canal. Within the alimentary canal,
      positively stained processes were found in the crop, midgut, and hindgut, and
      immunoreactive endocrinelike cells were located in the midgut. In situ
      hybridization with a digoxigenin-labeled RNA probe spanning the entire LMS coding
      region showed cell bodies containing LMS mRNA in all ganglia studied, other than
      the ingluvial ganglion. Expression was most abundant in the brain and optic lobes
      and in the frontal and suboesophageal ganglia. LMS mRNA was also apparent,
      although less intensely, in all other ganglia of the ventral nerve cord. Within
      the alimentary canal, LMS mRNA-positive cells were only visible in the anterior
      portion of the midgut, in the endocrinelike cells. The appearance of LMS mRNA in
      the central nervous system, stomatogastric nervous system, and midgut suggests
      that LMS may play a central role in Diploptera and may be associated with feeding
      and digestion.

PMID- 9596528
TI  - Regulation of MCSF receptors on microglia in the normal and injured mouse central
      nervous system: a quantitative immunofluorescence study using confocal laser
      microscopy.
AB  - The macrophage colony-stimulating factor (MCSF) is a 40-76-kD glycoprotein that
      plays an important role in the activation and proliferation of microglia both in
      vitro and in injured neural tissue. Here, we examined the regulation of MCSF
      receptor (MCSFR) and MCSF in the normal and injured mouse central nervous system
      (CNS) by using confocal laser microscopy, quantitative immunofluorescence, and
      reverse transcriptase-polymerase chain reaction (RT-PCR) techniques.
      Immunohistochemistry on fixed, floating tissue sections demonstrated low to
      moderate MCSFR immunoreactivity (MCSFR-IR) on microglia in the gray and white
      matter throughout the mouse CNS in the forebrain, brainstem, cerebellum, and
      spinal cord. High levels of MCSFR-IR were restricted to the superficial layer of
      the spinal cord dorsal horn, substantia nigra, and area postrema, a CNS region
      that lacks the blood-brain barrier. CNS injury led to a strong and specific
      increase in MCSFR-IR in the directly injured dorsal forebrain, in the cervical
      spinal cord (C2) after transection of the sensory, minor occipital nerve, and in
      the axotomized facial motor nucleus. Further investigation at the mRNA level in
      the facial nucleus model showed that this increase was accompanied by a rapid
      induction of the transcript for MCSFR, with a peak 1-2 days after injury, but
      only a constitutive expression of MCSF-mRNA. In summary, although normal levels
      of MCSF receptor in most microglia are low, microglial activation is accompanied
      by a rapid and massive increase. In view of the constitutive expression of MCSF,
      the early upregulation of the MCSF receptor may play a central role in preparing
      these macrophage-related cells to take part in the cellular response to CNS
      injury.

PMID- 9596529
TI  - Nigral innervation of cholinergic and glutamatergic cells in the rat mesopontine
      tegmentum: light and electron microscopic anterograde tracing and
      immunohistochemical studies.
AB  - The substantia nigra (SN) has long been known as an important source of afferents
      to the pedunculopontine tegmental nucleus (PPN). However, it has not been
      established which of the chemospecific cell populations receive this synaptic
      input. We sought to address this issue by a correlative light and electron
      microscopic approach that combines anterograde tracing of nigral efferents with
      pre-embedding choline acetyltransferase (ChAT) and/or glutamate (Glu)
      immunohistochemistry. Following large bilateral injections of Phaseolus vulgaris
      leucoagglutinin (PHA-L) in the SN, the labeled nigrotegmental fibers were
      concentrated in a small area of the mesopontine tegmentum which contained very
      few ChAT-immunoreactive (ChAT-ir) cell bodies. However, strands of fine varicose
      fibers penetrated to adjacent regions of the PPN which harbored numerous
      cholinergic perikarya. The anterogradely labeled boutons were often seen in the
      proximity of ChAT-ir perikarya and dendrites, but the majority (82-93%)
      established symmetric synaptic junctions with noncholinergic profiles. In the
      pars dissipata of the PPN (PPNd), one-third of the labeled terminals synapsed
      onto noncholinergic perikarya and primary dendrites, while in the pars compacta
      of the PPN (PPNc) axosomatic synapses were rare. The possibility that the
      perikarya receiving a rich synaptic input from the SN are glutamatergic was
      tested in experiments combining anterograde transport of biotinylated tracers
      biocytin and dextran-amine (BDA) with glutamate immunohistochemistry. In double
      labeled sections, Glu-ir perikarya within the terminal plexus of nigrotegmental
      fibers were surrounded by synaptic terminals. The PPNd also contained
      retrogradely BDA-labeled neurons which were contacted by anterogradely labeled
      terminals. These results indicate that although a small subpopulation of
      cholinergic neurons in the mesopontine tegmentum receive direct synaptic input
      from the SN, the primary target of nigrotegmental fibers are glutamatergic cells
      in the PPNd. Our results also provide ultrastructural evidence that some
      nigrotegmental fibers innervate pedunculonigral neurons.

PMID- 9596530
TI  - Organization of the dorsocaudal neostriatal complex: a retrograde and anterograde
      tracing study in the domestic chick with special emphasis on pathways relevant to
      imprinting.
AB  - In the forebrain of domestic chicks, a network of distinct regions is crucially
      involved in auditory and visual filial imprinting. Among these areas, a distinct
      part of the dorsocaudal neostriatal complex (dNC complex), termed neostriatum
      dorsocaudale (Ndc), was recently discovered by its enhanced metabolic activity
      during the presentation of auditory and visual imprinting stimuli. Since there is
      evidence that the dNC complex consists of several distinct functional subareas,
      we investigated the neural connections of different parts of the dNC complex by
      retro- and anterograde pathway tracing. Special emphasis was put on the
      connections of the dNC complex with other imprinting relevant regions in the
      rostral telencephalon, such as the mediorostral neostriatum/hyperstriatum
      ventrale (MNH) and the intermediate and medial part of the hyperstriatum ventrale
      (IMHV). By anterograde and multiple retrograde pathway tracing, we found that the
      dNC complex may at least be subdivided into three major constituents. The most
      medial part of the dNC complex, termed neostriatum dorsale (Nd), is characterized
      by strong reciprocal connections with the neostriatal part of the MNH and by its
      auditory related inputs, including those from the output layers L1 and L3 of
      field L, and the shell region of the thalamic n. ovoidalis. The Ndc, which
      occupies the central aspects of the dNC complex, is mainly characterized by
      reciprocal connections with the ectostriatal belt (Ep) and the adjacent
      neostriatum (N). Furthermore, Nd and Ndc receive strong thalamic input from the
      n. dorsolateralis posterior (DLP), both project to the IMHV, and both are
      reciprocally connected with the archistriatum intermedium (AI). The most lateral
      aspect of the dNC complex, termed Ndl, is characterized by afferents from the
      neostriatum frontale, pars trigeminalis (NFT), and by the lack of a thalamic
      input. Results indicate that the dNC complex comprises distinct subregions, which
      are characterized by their specific afferents from parasensory areas of different
      sensory modalities. These different subregions may be integral components of a
      general pattern of sensory processing in the avian telencephalon. The strong
      interconnections between Nd, Ndc, and MNH as well as IMHV may constitute
      essential parts of auditory and visual imprinting circuits.

PMID- 9596531
TI  - Local circuit for the computation of object approach by an identified visual
      neuron in the locust.
AB  - The lobula giant movement detector (LGMD) neuron in the locust visual system is
      part of a motion-sensitive pathway that detects objects approaching on a
      collision course. Here we show that the retinotopic units presynaptic to the LGMD
      make synapses directly with each other and these synapses are immediately
      adjacent to their outputs onto the LGMD. Synapses occur along the fine dendrites
      of the LGMD in the distal lobula, often in large numbers and completely covering
      the LGMD processes. Gamma aminobutyric acid (GABA) was eliminated as a possible
      neurotransmitter at these synapses when immunogold-tagged monoclonal GABA
      antibody did not specifically label the afferent processes. We used a
      histochemical method to demonstrate that acetylcholine esterase, the enzyme that
      hydrolyses acetylcholine at cholinergic synapses, was present in the synaptic
      clefts between the retinotopic units and along the membrane of the LGMD. It is
      well established that acetylcholine has both excitatory and inhibitory effects
      and we propose that these retinotopic units excite the LGMD, but inhibit each
      other; and that the synapses form the substrate for a critical race between
      excitation caused by edges moving out over successive photoreceptors, and
      inhibition spreading laterally. This results in the selective response to objects
      approaching on a collision course.

PMID- 9596532
TI  - Common protective movements govern unexpected falls from standing height.
AB  - Simple energy considerations suggest that any fall from standing height has the
      potential to cause hip fracture. However, only 1-2% of falls among the elderly
      actually result in hip fracture, and less than 10% cause serious injury. This
      suggests that highly effective movement strategies exist for preventing injury
      during a fall. To determine the nature of these, we measured body segment
      movements as subjects (aged 22-35 yr) stood upon a gymnasium mattress and
      attempted to prevent themselves from falling after the mattress was made to
      translate abruptly. Subjects were more than twice as likely to fall after
      anterior translations of the feet, when compared to posterior or lateral
      translations. In falls which resulted in impact to the pelvis, a complex sequence
      of upper extremity movements allowed subjects to impact their wrist at nearly the
      same instant as the pelvis (average time interval between contacts = 38 ms),
      suggesting a sharing of contact energy between the two body parts. Finally,
      marked trunk rotation was exhibited in falls due to lateral (but not anterior or
      posterior) perturbations, resulting in the avoidance of impact to the lateral
      aspect of the hip. These results suggest that body segment movements during
      falls, rather than being random and unpredictable, involve a repeatable series of
      responses which facilitate safe landing.

PMID- 9596533
TI  - Experimental analysis of unsteady flows through a stenosis.
AB  - In this paper we present a study of the post-stenotic velocity flow field
      corresponding to oscillatory, pulsatile and physiological flow waveforms. Two
      dimensional velocity measurements are performed in a 75% severity stenosis using
      a pulsed Doppler ultrasonic velocimeter. Emphasis is placed on the analysis of
      the experimental velocity-profile patterns. It is recognized that, beyond the
      influence of the flow parameters such as the Reynolds number and the frequency
      parameter, velocity profiles (hence wall-shear stresses) highly depend on the
      flow waveform. In addition to this analysis, a model of the stenosis influence
      length is proposed in the case of oscillatory flow.

PMID- 9596534
TI  - Using cine phase contrast magnetic resonance imaging to non-invasively study in
      vivo knee dynamics.
AB  - We tested the accuracy and feasibility of using cine phase contrast magnetic
      resonance imaging (cine-PC MRI) to non-invasively measure three-dimensional, in
      vivo, skeletal velocity. Bone displacement was estimated by integrating the
      velocity measurements. Cine-PC MRI was originally developed to directly and non
      invasively measure in vivo blood and heart velocity. Since no standard of
      reference exists for in vivo measurement of trabecular bone motion, a motion
      phantom (consisting of a series of paired gears that moved a sample box
      containing a human femoral bone sample) was built to assess the accuracy of
      tracking trabecular bone with cine-PC MRI. The in-plane, average absolute
      displacement errors were 0.55 +/- 0.38 and 0.36 +/- 0.27 mm in the x- and y
      direction, respectively. Thus, estimates of bone position based on the
      integration of bone velocity measurements are affected little by the magnetic
      properties of bone [Majumdar and Genant (1995) Osteoporos International 5, 79
      92]. The velocity profiles of the patella, femur and tibia were measured in five
      healthy subjects during leg extensions. Extension was resisted by a 34 N weight.
      Subjects maintained a consistent motion rate (35 +/- 0.5 cycles min(-1)) and
      motion artifacts were minimal. Our results indicate that patellar flexion lags
      knee flexion and the patella tilts laterally and then medially as the knee
      extends. We conclude cine-PC MRI is a promising technique for the non-invasive
      measurement of in vivo skeletal dynamics and, based on our previous work,
      muscular dynamics as well.

PMID- 9596535
TI  - Removing swing from a handstand on rings using a properly timed backward giant
      circle: a simulation solution.
AB  - In the rings event in men's gymnastics, marks are deducted if the rings and
      gymnast are swinging during a held handstand position. The unwanted swing can be
      reduced in the next handstand position if the gymnast is able to properly time
      the start of the connecting giant circle. The purpose of this study was to search
      for the optimal time to commence a backward giant circle in order to attenuate
      swing in the succeeding handstand. Computer simulations, using a four-segment and
      a three-segment model which employed two-pulse muscular control strategies, were
      used to search for the optimal timing solution. Qualitative validation tests
      between the performance of a world class gymnast and the simulation models
      indicated that a three-segment model comprising a cables-rings segment, an arms
      segment with a shoulder torque generator, and a head-torso-legs segment, produced
      similar results to that of a four-segment model which separated the legs segment
      from the torso and employed an additional torque generator at the hip joint. The
      results from the simulation indicated that a gymnast should be advised to
      initiate a backward giant circle when his swinging handstand has reached the
      bottom of its swing-arc. For a handstand with an original swing-amplitude of 10
      degrees, the simulation results indicate that a properly timed backward giant
      circle can reduce this amplitude to a negligible 1.5 degrees of swing.

PMID- 9596536
TI  - Quantification of in vivo patellofemoral contact forces before and after ACL
      transection.
AB  - Altered knee loading following anterior cruciate ligament (ACL) transection is
      believed to play an important role in initiating cartilage degeneration. Changes
      of in vivo joint contact forces pre- and post-ACL transection have not been
      quantified to date. Consequently, it is not known how knee loading changes
      following ACL transection, and how it contributes to cartilage degeneration. The
      objective of this study was to quantify in vivo patellofemoral contact forces in
      the cat knee prior to and up to nine days following uni-lateral ACL transection.
      Patellofemoral contact forces were predicted using a planar three-force model
      with knee extensor forces and patellofemoral geometry as input. Patellofemoral
      movements were expressed as functions of external knee kinematics. Kinematics and
      knee extensor forces were measured in both hindlimbs before and after ACL
      transection during unrestrained locomotion. Following ACL transection, resultant
      patellofemoral contact forces were decreased by approximately 30% in the ACL
      deficient hindlimbs. These results suggest that decreased loading in the ACL
      deficient knees may initiate the early degenerative changes observed in cartilage
      of ACL-transected animals. It remains to be shown, if the general unloading of
      the joint also results in locally decreased contact loads and altered joint
      kinematics. Alterations of in vivo patellofemoral loading following ACL
      transection have been quantified for the first time in this study. A next step
      will be to quantify the dynamic in vivo cartilage stresses in intact and injured
      knees which may help to elucidate the effects of mechanical stimuli on cartilage
      metabolism.

PMID- 9596537
TI  - Hemodynamics of endovascular prostheses.
AB  - A surgical study (Bergeron et al., 1991, International Angiology 10(3), 182-186)
      picked out that re-endothelialization of implanted expandable stents, frequently
      used to reduce the recurrent stenosis rate after balloon angioplasty, was correct
      and more rapid in femoro-popliteal arteries (quasi-straight vessels) than in
      iliac arteries (bifurcated vessels). Since it is now well known that local
      hemodynamics are considered to be an important atherogenic factor, we decided to
      compare and optimize the shape of the existing equipment, in order to further
      give some informations to surgeons about the optimal stenting at the site of
      bifurcation. Therefore, we studied in vitro (1) the influence of the protruding
      part of a stent on the flow patterns in the branches of an aorto-iliac
      bifurcation model, and (2) the possibility of reducing or preventing this impact.
      Qualitative information was obtained from visualizations in the horizontal median
      plane of the bifurcation model, while Doppler ultrasonic velocimetry provided
      quantitative data, at different points of the cardiac cycle. Results showed that
      a standard stent implanted in a daughter branch of the bifurcation may have a
      considerable influence on flow behaviour when it is sticking out of the daughter
      branch. A new design of stent, with a bevelled shape, showed a significant
      reduction of flow disturbance.

PMID- 9596538
TI  - Reduction in tensile strength of cartilage precedes surface damage under repeated
      compressive loading in vitro.
AB  - An experimental protocol for the fatiguing and tensile testing of articular
      cartilage has been established. Samples were taken from the interpatellar groove
      of bovine femurs collected post-slaughter, split into two test groups and
      subjected to a cyclically varying compressive load of approximately 65 N for
      64,800 cycles or 97,200 cycles. The cartilage was then removed from the
      underlying bone and two specimens, one from the indented region and one from an
      unindented region - the control, were taken from it and prepared for subsequent
      tensile testing using notched specimens. From data collected during tensile
      testing, a value of maximum tensile stress was calculated for each sample. The
      underlying bone was examined for evidence of microdamage using the basic fuchsin
      method. A decrease in values of maximum tensile stress (p < 0.05) for the
      indented sample of each paired group of samples loaded for 97,200 cycles was
      found. In contrast, those fatigued for only 64,800 cycles showed no such
      difference. Examination of the underlying bone of these specimens revealed no
      evidence of trabecular failure and crack formation beneath both the indented and
      control regions. It is postulated that the fatiguing process used in this
      experiment induces trauma in the cartilage causing a weakening of the interfibril
      connections which link collagen fibrils in the matrix, leading to a reduction in
      tensile strength. This weakening occurs, however, without the appearance of
      fibrillation on the cartilage surface or any evidence of failure in the bony
      structure which supports it.

PMID- 9596539
TI  - Validation of a lower limb model with in vivo femoral forces telemetered from two
      subjects.
AB  - A mathematical model of the human pelvis-leg system in the sagittal plane, with
      an anatomical model of the knee, was developed to calculate forces transmitted by
      the structural elements of the system. The model was used to study the influence
      of activity of hip flexors and extensors on the forces in the femur during
      isometric exercises and during level walking. Kinematic and kinetic data together
      with simultaneous electromyography (EMG) and in vivo axial forces transmitted
      along the prostheses from two patients implanted with instrumented massive
      proximal femoral prostheses were obtained. Comparison of the levels of the
      calculated axial forces in the model femur to the simultaneous telemetered forces
      showed good agreement for isometric tests. Interaction between the muscles and
      the bones during isometric tests was examined and bi-articular muscles were shown
      to play a major role in modulating forces in bones. The study supports the
      hypothesis that muscles balance the external limb moments, not only at joints but
      also along the limbs, decreasing the bending moments but increasing the axial
      compressive forces in bones. It is thus suggested that appropriate simulation of
      muscle force is necessary in in vitro laboratory experiments and in theoretical
      studies of load transmission in bones. The sagittal plane model underestimates
      the value of the maximum axial force in the femur during walking by about 30% but
      suggests that 70% was due to the action of the extensors or flexors. The results
      encourage further development of a three-dimensional model with anatomical models
      of the joints to include coronal and transverse planes for the study of adductors
      and abductors.

PMID- 9596540
TI  - In vivo human knee joint dynamic properties as functions of muscle contraction
      and joint position.
AB  - Information on the dynamic properties (joint stiffness, viscosity and limb
      inertia) of the human knee joint is scarce in the literature, especially for
      actively contracting knee musculature. A joint driving device was developed to
      apply small-amplitude random perturbations to the human knee at several flexion
      angles with the subject maintaining various levels of muscle contraction. It was
      found that joint stiffness and viscosity increased with muscle contraction
      substantially, while limb inertia was constant. Stiffness produced by the
      quadriceps was highest at 30 degrees flexion and decreased with increasing or
      decreasing flexion angle, while knee flexors produced highest stiffness at 90
      degree flexion. When knee flexion was < 60 degrees, stiffness produced by the
      quadriceps was higher than that of the hamstrings and gastrocnemius at the same
      level of background muscle torque, while knee flexor muscles produced higher
      stiffnesses than the quadriceps at 90 degree flexion. Similar but less obvious
      trends were observed for joint viscosity. Passive joint stiffness at full knee
      extension was significantly higher than in more flexed positions. Surprisingly,
      as the knee joint musculature changed from relaxed to contracting at 50% MVC,
      system damping ratio remained at about 0.2. This outcome potentially simplifies
      neuromuscular control of the knee joint. In contrast, the natural undamped
      frequency increased more than twofold, potentially making the knee joint respond
      more quickly to the central nervous system commands. The approach described here
      provides us with a potentially valuable tool to quantify in vivo dynamic
      properties of normal and pathological human knee joints.

PMID- 9596541
TI  - A three-dimensional musculoskeletal database for the lower extremities.
AB  - A three-dimensional musculoskeletal database of the lower extremities has been
      developed for use in human musculoskeletal models. The locations of idealized
      muscle attachments on the pelvis, both femurs, both tibias and fibulas, and both
      feet were accurately digitized for 52 dried skeletal specimens. The mean specimen
      heights were 177.5 cm (male) and 166.2 cm (female) and the mean specimen age at
      the time of death was 48.8 yr. Statistical accumulation and scaling techniques
      were used to generate highly representative normative models, which were divided
      into groups and tested for differences based on gender and race. From the test
      results, the pelvis was divided into a male model (RMS = 8.6 mm), a black female
      model (RMS = 7.0 mm) and a white female model (RMS = 7.3 mm). The foot was
      separated into black (RMS = 3.7 mm) and white models (RMS = 3.6 mm). Single
      models were used for the femur (RMS = 6.5 mm) and the tibia/fibula (RMS = 3.7).
      Containing over 12000 anatomical landmarks digitized from 52 dried skeletons,
      this study represents an improvement over previous databases by an order of
      magnitude.

PMID- 9596542
TI  - Ultrastructure and tensile properties of human tracheal cartilage.
AB  - The cartilage of the walls of the trachea and bronchi acts to keep these airways
      open despite intrathoracic pressure differences during breathing that would
      otherwise collapse them and limit air flow. Changes in biomechanical properties
      and composition of airway cartilage may contribute to altered lung function in
      obstructive lung diseases. To investigate the relationship between collagen
      organization and equilibrium tensile modulus within the structure of airway
      cartilage, we used scanning electron microscopy (SEM), histochemistry and
      equilibrium tensile testing to analyze tracheal cartilage from 10 humans aged 17
      81 yr. We show that the surfaces of tracheal cartilage matrix are collagen-rich
      and surround a proteoglycan-rich core. Collagen fibrils in the superficial zones
      are oriented in the plane of the cartilage surface. In deeper layers of the
      cartilage, collagen fibrils are oriented less regularly. Equilibrium tensile
      modulus of 100 microm thick strips of cartilage was measured and was found to
      decrease with depth; from 13.6 +/- 1.5 MPa for the ablumenal superficial zone to
      4.6 +/- 1.7 MPa in the middle zone (means +/- S.D., n = 10, p < 0.001). Stress
      strain curves were linear for strains up to 10% with minimal residual strain.
      This is consistent with a model in which collagen fibres in the outer layers of
      the cartilage resist tensile forces, and hydrated proteoglycans in the central
      zone resist compression forces as the cartilage crescent bends.

PMID- 9596543
TI  - Improved extrapolation techniques in recursive digital filtering: a comparison of
      least squares and prediction.
AB  - Two extrapolation techniques for recursive digital filtering are presented and
      compared with common padding methods such as linear and reflection (reverse
      mirror) extrapolation. The case in which the endpoints of position data lead to
      peak accelerations after filtering and differentiation is examined. The first
      technique, 'least squares', is based on fitting a third-degree polynomial to the
      final 10 data points in both the forward and backward directions and extending
      the signal by 20 data points using the polynomial coefficients. The second
      technique, 'prediction', is based on a linear autoregressive model with 20
      coefficients, which is applied in both directions and the signal is extrapolated
      by 20 points. The lowest cumulative error of the endpoint accelerations (22.8 rad
      s(-2)) represented just one-third of the error when the common padding methods
      were used in optimal digital filtering (69.7 rad s(-2)). It also represented
      approximately half the lowest cumulative error in optimal smoothing with quintic
      splines (48.0 rad (s-2)).

PMID- 9596544
TI  - In vivo estimation of the glenohumeral joint rotation center from scapular bony
      landmarks by linear regression.
AB  - In this paper, a method is described for in vivo prediction of the glenohumeral
      joint rotation center (GH-r), necessary for the construction of a humerus local
      coordinate system in shoulder kinematic studies. The three-dimensional positions
      of five scapula bony landmarks as well as a large number of data points on the
      surface of the glenoid and humeral head were collected at 36 sets of cadaver
      scapulae and adjacent humeri. The position of GH-r in each scapula was estimated
      by mathematically fitting spheres to the glenoid and humeral head. GH-r
      prediction from scapula geometry parameters by linear regression resulted in a
      RMSE between measured and predicted GH-r of 2.32 mm for the x-coordinate, 2.69 mm
      for the y-coordinate and 3.04 mm for the z-coordinate. Application in vivo
      revealed a random humerus orientation error due to measurement inaccuracies of
      1.35, 0.29 and 1.26 degrees standard deviation per rotation angle. The estimated
      total humerus orientation error including the offset error due to the regression
      model inaccuracy was 2.86, 0.84 and 2.69 degrees standard deviation. As these
      errors were about 15 and 20% of, respectively, the intra- and inter-subject
      variability of the humerus orientations measured, it is concluded that the method
      described in this paper allows for an adequate construction of a humerus local
      coordinate system.

PMID- 9596545
TI  - Efficient calculation of mass moments of inertia for segmented homogeneous three
      dimensional objects.
AB  - The equations for the volume, centroid, and mass moments of inertia of a three
      dimensional object are derived using Green's theorem. The object is assumed to be
      homogeneous and described as a stack of two-dimensional cross-sections. Given
      these assumptions, our approach using Green's theorem dramatically decreases data
      manipulation and computation as compared to the classical mass element summation
      technique employed for three-dimensional discrete objects. Although numerous
      factors influence accuracy, we chose to evaluate two representative objects in
      two orientations to determine the influence of the number of two-dimensional
      cross-sections on the accuracy of the calculations. For these shapes, 15 cross
      sections per object were required to achieve relative error below 1%.

PMID- 9596546
TI  - Remarks on the technical note entitled 'Temporal stability of node-based internal
      bone adaptation simulations'.

PMID- 9596547
TI  - Evolving standards in arthritis therapy. IX EULAR Symposium, October 7, 1996,
      Madrid, Spain. Introduction.

PMID- 9596548
TI  - Scientific rationale for specific inhibition of COX-2.
AB  - Cyclooxygenase (COX) is the principal enzyme involved in the production of
      prostaglandins. Inhibition of COX is also the primary mechanism of action of
      aspirin and other nonsteroidal antiinflammatory drugs (NSAID). Since
      prostaglandins are important regulators of cellular function, inhibition of
      prostaglandin production may lead to adverse effects. Two isoforms of COX have
      been identified, sequenced, and cloned. COX-1 is constitutively produced and is
      believed to be involved in regulating normal cellular processes, such as
      gastrointestinal (GI) cytoprotection, vascular homeostasis, and renal function.
      In contrast, COX-2 -- the inducible form -- is undetectable in most tissues but
      is present in inflamed tissue. Evidence therefore suggests that the GI toxicity
      associated with NSAID use is primarily the result of inhibition of COX-1, and
      antiinflammatory effects are largely due to inhibition of COX-2. A drug that
      specifically inhibits COX-2 without affecting COX-1 would, theoretically, reduce
      inflammation without leading to GI side effects. A variety of biologic assays
      have been developed to characterize the relative activities of NSAID against COX
      1 and COX-2. Such in vitro testing has demonstrated that individual NSAID possess
      different relative inhibitory effects in various tissues. Several NSAID have been
      reported to show more potent inhibition of COX-2 than of COX-1 in vitro; however,
      the clinical relevance of differential inhibition of COX isozymes is as yet
      unknown. Some clinical studies indicating reduced toxicity for these NSAID may,
      in fact, be attributable to use of these agents at subtherapeutic doses. As yet,
      no clinically available NSAID has been shown to have significant in vivo effects
      on COX-2 while sparing COX-1 activity in humans. However, compounds that may be
      100 to 300-fold more effective inhibitors of COX-2 and that therefore may have
      lower risks for toxicity as well as more potent antiinflammatory effects have
      been developed, but are not yet available for clinical use.

PMID- 9596549
TI  - NSAID induced gastrointestinal complications: the ARAMIS perspective--1997.
      Arthritis, Rheumatism, and Aging Medical Information System.
AB  - Gastrointestinal (GI) complications related to nonsteroidal antiinflammatory drug
      (NSAID) therapy are the most prevalent category of adverse drug reactions.
      Patients with arthritis are among the most frequent users of NSAID and are
      therefore particularly at risk for these side effects. To evaluate the nature of
      NSAID related GI complications and to determine how their frequency can be
      reduced, a series of studies of such complications in patients with rheumatic
      disease has been carried out based on data from the Arthritis, Rheumatism, and
      Aging Medical Information System (ARAMIS). We review the literature and present
      findings from the ARAMIS studies. This report addresses whether GI side effects
      such as dyspepsia can serve as warning symptoms for serious GI complications and
      describes the risk factors for these life threatening complications. It also
      describes differences among NSAID with regard to their GI toxicity and describes
      a study that investigated whether H2-receptor antagonists and antacids affect the
      development of serious GI complications. In addition, ongoing research and topics
      to be addressed in future studies are described.

PMID- 9596550
TI  - Prevention of gastrointestinal complications associated with nonsteroidal
      antiinflammatory drugs.
AB  - Nonsteroidal antiinflammatory drugs (NSAID), although used frequently for the
      treatment of arthritis and musculoskeletal disorders, may produce deleterious
      effects related to the gastrointestinal (GI) tract, including dyspeptic symptoms,
      erosions, ulcers, and serious GI complications (i.e., bleeding, perforation, and
      gastric outlet obstruction). Endoscopic studies with the synthetic prostaglandin
      E1 analog misoprostol, various acid-reducing agents (e.g., H2 receptor
      antagonists and proton pump inhibitors), and surface-active drugs such as
      sucralfate, have been shown to prevent NSAID induced gastric and/or duodenal
      ulcers. The Misoprostol Ulcer Complication Outcomes Safety Assessment (MUCOSA)
      trial was a 6 month, randomized, double blind, placebo controlled study to
      investigate whether concurrent administration of misoprostol would significantly
      reduce the occurrence of serious upper GI complications in patients with
      rheumatoid arthritis (RA) who were receiving NSAID. Results showed that overall
      complications were reduced by 40% (p = 0.049) among patients receiving
      misoprostol (25 patients with definite serious GI events among 4404 patients
      treated) compared with those receiving placebo (42 out of 4439 patients). Thus,
      cotherapy with misoprostol resulted in a statistically significant reduction in
      the incidence of serious NSAID induced upper GI complications compared with
      placebo in patients with RA.

PMID- 9596551
TI  - Diclofenac/misoprostol: the European clinical experience.
AB  - OBJECTIVE: The fixed combination of diclofenac sodium and misoprostol (Arthrotec)
      is the only nonsteroidal antiinflammatory drug (NSAID) that contains a
      gastroprotective component and is available in 2 formulations:(1) an enteric
      coated core of diclofenac sodium 50 mg surrounded by a mantle of misoprostol 200
      microg, and (2) a 75 mg enteric coated diclofenac core also surrounded by a 200
      microg mantle of misoprostol. This article reviews the European clinical
      experience with both formulations in patients with arthritis. METHODS: Three
      randomized, blinded, multicenter studies, including one in general practice,
      evaluated the efficacy of combination diclofenac/misoprostol versus diclofenac or
      ibuprofen in a total of 1824 patients with rheumatoid arthritis (RA) or
      osteoarthritis (OA). Four additional studies assessed antiarthritic efficacy and
      employed endoscopy to compare the gastroduodenal safety of combined
      diclofenac50/misoprostol with that of diclofenac, naproxen, piroxicam, or
      indomethacin in 1459 patients with RA, OA, or ankylosing spondylitis. The
      gastroduodenal safety and antiarthritic efficacy of diclofenac75/misoprostol was
      compared with that of diclofenac in one endoscopy study involving 514 patients
      with RA or OA. RESULTS: The efficacy and safety data obtained from these European
      clinical trials show that both formulations diclofenac50/misoprostol and
      diclofenac75/misoprostol are effective antiinflammatory drugs, with clinical
      efficacy equivalent to that of diclofenac. Diclofenac50/misoprostol is at least
      as effective as naproxen, piroxicam, indomethacin, and ibuprofen. Both
      formulations of the combination were associated with significantly fewer
      gastroduodenal ulcers compared with diclofenac. In separate studies, the
      tolerability of diclofenac50/misoprostol (as determined by withdrawal rates) was
      shown to be equivalent to that of diclofenac, naproxen, piroxicam, and ibuprofen,
      and the tolerability of diclofenac75/misoprostol was shown to be equivalent to
      that of diclofenac. The diclofenac50/misoprostol was associated with fewer
      decreases in hemoglobin concentration compared with diclofenac in the general
      practice study as well as in hospital patients. CONCLUSION:
      Diclofenac50/misoprostol and diclofenac75/misoprostol are effective in treating
      the signs and symptoms of RA and OA and are well tolerated by the majority of
      patients. Both of these formulations achieve a significant reduction in the
      incidence of both gastric and duodenal ulcers compared with other NSAID.

PMID- 9596552
TI  - Diclofenac/misoprostol: novel findings and their clinical potential.
AB  - The new class of antiinflammatory and analgesic drugs, the selective
      cyclooxygenase (COX-2) inhibitors, which promise to be devoid of the types of
      toxicity associated with nonsteroidal antiinflammatory drugs (NSAID), especially
      adverse gastrointestinal effects, are under clinical trial but are not yet
      available for use. All NSAID, including those most recently introduced, exhibit
      nonselectivity of action, producing therapeutic blood levels that inhibit
      constitutive COX-1 and deplete tissue protective prostaglandins. Among NSAID, the
      diclofenac/misoprostol combination (Arthrotec) is unique in possessing an active
      component, misoprostol, to help prevent NSAID induced gastrointestinal damage.
      Ulcer damage and associated serious complications probably represent only the tip
      of the iceberg in relation to clinically significant side effects associated with
      the use of NSAID. In this context, metaanalysis of 8 large multicenter studies
      reported here has shown that patients taking NSAID show a mean decrease in
      hemoglobin over 4 - 12 weeks' assessment, with some 10-20% of patients exhibiting
      clinically significant decreases (> or = 1 g/dl) early in treatment. Patients
      taking diclofenac/misoprostol showed significantly less of a decline in
      hemoglobin and up to 50% fewer clinically significant decreases than patients
      receiving diclofenac alone. The misoprostol component of diclofenac/misoprostol
      may also help to restore homeostasis in tissues other than the gut. Inhibition of
      the activity or release of various tissue damaging agents and inflammatory
      cytokines, e.g., thromboxane and interleukin 1, are described, as are in vivo
      animal studies that have revealed synergistic or potentiating analgesic and
      antiinflammatory activities between misoprostol and NSAID, particularly
      diclofenac. Clinical studies in postsurgical dental pain in more than 500
      patients have now shown enhanced analgesia, with greater relief over a longer
      period, for the diclofenac/misoprostol combination compared with diclofenac
      alone. The relevance of these findings to pain and inflammation control in
      arthritis is discussed. Enhanced control of morning stiffness provided by
      diclofenac/misoprostol, possibly also the result of misoprostol/diclofenac
      synergy, is also reported, and the development of an objective system that
      measures 24 hour ambulatory activity is described. Using this Numact recorder,
      improved mobility in patients receiving diclofenac 75 mg/misoprostol 200 microg
      was observed compared with patients treated with diclofenac 75 mg slow release.
      Further studies are being performed employing magnetic resonance imaging both to
      assess antiinflammatory effects in joint soft tissue architecture and to assess
      whether the synergistic stimulatory effects of diclofenac and misoprostol on
      human osteoarthritic cartilage that have been reported in vitro are clinically
      evident. A growing body of evidence supports the view that the
      diclofenac/misoprostol combination provides an improved therapeutic ratio over
      diclofenac alone, not only by improving gastrointestinal safety but also by
      enhancing analgesic/antiinflammatory effects.

PMID- 9596553
TI  - Vinblastine enhancement of hyposmosis-induced catecholamine release in cultured
      adrenal chromaffin cells: lack of relation to cell swelling and microtubule
      disruption.
AB  - Exposure of chromaffin cells to hyposmotic solution has been shown to cause
      catecholamine release through the elevation of intracellular Ca2+ level. While
      cell volume change observed under hyposmotic conditions has been shown to be
      accompanied by the movement of various ions and suggested to be associated with
      the reorganization of cytoskeletons. In the present study, the effects of
      cytoskeleton-disrupting agents on hyposmosis-induced catecholamine release were
      examined to investigate a possible relationship between catecholamine release and
      cell volume change under hyposmotic conditions. Hyposmosis-induced catecholamine
      release was enhanced by pre-treatment of the cells with a microtubule-disrupting
      agent vinblastine, but not significantly altered by a microfilament-disrupting
      agent cytochalasin B. Vinblastine also caused an additional increase in the
      intracellular Ca2+ but failed to affect the cell volume change under hyposmotic
      conditions. In contrast, the hyposmosis-induced release was not significantly
      altered by either colchicine, another microtubule-disrupting agent, or taxol, a
      microtubule-stabilizing agent. These results indicate that vinblastine enhances
      hyposmosis-induced catecholamine release through an additional increase in the
      intracellular Ca2+ and furthermore suggest that this effect of vinblastine on the
      hyposmosis-induced release is unassociated with the disruption of the microtubule
      system, providing evidence for a lack of the direct relationship between
      catecholamine release and the cell volume change observed under hyposmotic
      conditions.

PMID- 9596554
TI  - Neurotoxicity of cholesterol oxides on cultured cerebellar granule cells.
AB  - Cultured rat cerebellar granule cells were used to determine the potential
      neurotoxicity of cholesterol oxides. The cholesterol oxides tested included: 7
      beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH- and 25-OH- cholesterol. Among
      them, 7-beta-OH- and 7-keto-cholesterol were the most efficacious in causing
      neuronal death such that 20 microg/ml (50 microM) of these agents killed more
      than 80% of cells in 2 days. 7-beta-OH-cholesterol at this concentration killed
      50% of cells in approximately 7 h. A number of pharmacological agents were tested
      for their abilities to prevent neuronal death induced by cholesterol oxides.
      Among them, aurintricarboxylic acid, vitamin E and methyl-beta-cyclodextrin were
      able to prevent cholesterol oxide-induced neurotoxicity in a dose-dependent
      manner. These results suggest that, in addition to causing pathological changes
      in cells directly involved in atherosclerosis, cholesterol oxides may induce
      toxicity in neurons of the central nervous system.

PMID- 9596555
TI  - Possible in vivo crosstalk between transcription factors with zinc-finger and
      leucine-zipper motifs in murine peripheral but not central excitable tissues.
AB  - In eukaryotes, de novo synthesis of proteins is mainly under control at the level
      of gene transcription by nuclear transcription factors with unique protein motifs
      such as leucine-zipper and zinc-finger. Binding of radiolabeled oligonucleotide
      probes for the "leucine-zipper" transcription factors, including activator
      protein-1 (AP1) and cyclic AMP response element binding protein (CREB), was
      markedly reduced in nuclear extracts of the adrenals from mice sacrificed 2 h
      after the subcutaneous injection of triamcinolone acetonide (TA), an agonist at
      glucocorticoid (GC) receptors which are also a transcription factor with "zinc
      finger" motifs. The reduction was most significant 2 h after the administration,
      with recovery to the control level within 7 h after the injection. Moreover, the
      administration of TA invariably doubled immunoreactivities to an antibody against
      human GC receptors in nuclear fractions of the adrenal, pituitary and
      hypothalamus, with a concomitant reduction of those in cytosol fractions. Similar
      inhibition by TA was also seen with AP1 binding in the pituitary, while TA did
      not affect binding of radioprobes for AP1 and CREB in any discrete brain
      structures. These results suggest that systemic TA signals may be preferentially
      transduced into cell nuclei to attenuate DNA binding activities of AP1 through
      molecular mechanisms associated with crosstalk between transcription factors with
      different protein motifs in murine peripheral but not central excitable tissues.

PMID- 9596556
TI  - Activation of sigma1 receptor subtype leads to neuroprotection in the rat primary
      neuronal cultures.
AB  - The mechanisms of sigma (sigma) receptor ligands-induced neuroprotective effects
      are controversial because both sigma receptors and phencyclidine (PCP) binding
      sites of the N-methyl-D-aspartate (NMDA) receptor channel complex have been
      reported to contribute to these neuroprotective effects. Thus, to clarify the
      role of sigma receptor in the neuroprotective effects, we examined the effects of
      1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503),
      a novel sigma1 receptor agonist with negligible affinity for the NMDA/PCP
      receptor channel complex, on the hypoxia/hypoglycemia- and exogenously applied
      NMDA-induced neurotoxicity in the rat primary neuronal cultures. A selective
      sigma1 receptor agonist, SA4503, significantly suppressed the
      hypoxia/hypoglycemia-induced neurotoxicity in the cultures, whereas this agonist
      failed to inhibit the NMDA-induced neurotoxicity. Similarly, (+)-pentazocine ((+)
      PTZ), a prototype sigma1 receptor agonist, inhibited the hypoxia/hypoglycemia
      induced neurotoxicity, whilst it did not affect the NMDA-induced toxicity in the
      cultures. These neuroprotective effects of SA4503 and (+)-PTZ were partially
      blocked by N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine
      monohydrochloride (NE-100), a putative sigma1 receptor antagonist. These results
      suggest that the sigma1 receptor subtype plays an important role in the sigma
      receptor ligands-induced neuroprotective effects via the regulation of excitatory
      amino acids (EAAs) release from the presynaptic sites.

PMID- 9596557
TI  - Protective effect of GV150526A on the glutamate-induced changes in basal and
      electrically-stimulated cytosolic Ca++ in primary cultured cerebral cortical
      cells.
AB  - Glutamate-induced changes in intracellular free Ca++ concentration ([Ca++]i) were
      recorded in resting and electrically-stimulated primary cultures of rat cerebral
      cortical cells, employing the Ca++ indicator Fura 2. A brief (10 min) exposure to
      glutamate led to a concentration-dependent basal [Ca++]i increase, measured 30
      min after glutamate removal. In order to unmask more subtle modifications in
      [Ca++]i movements associated with neurosecretion, the glutamate effect was also
      studied in electrically-stimulated cells. The application of trains (10 s) of
      electrical pulses (intensity 30 mA, duration 1 ms) induced frequency-related Na+-
      and Ca++-dependent [Ca++]i transients. A 5 min treatment with 50 microM glutamate
      reduced to 48% the electrically-evoked [Ca++]i transients, evaluated 30 min after
      glutamate challenge. The neuroprotective effect of sodium 4,6-dichloro-3-[(E)-3
      (N-phenyl)propenamide]indole-2-carboxylate (GV150526A), a new indole derivative
      with high affinity and selectivity for the glycine site of the NMDA receptor
      channel complex, was compared with that of DL-2-amino-5-phosphonopentanoic acid
      (AP5), ifenprodil, 7-chlorokynurenic acid and 2,3-dihydroxy-6-nitro-7
      sulfamoylbenzo(f)-quinoxaline (NBQX) on glutamate-induced [Ca++]i changes in
      resting and electrically-stimulated cells. In both experimental conditions,
      GV150526A showed to be the most potent compound. Moreover, GV150526A and 7
      chlorokynurenic acid were 2-3 times more active in stimulated neurons than in
      resting neurons, indicating a major involvement of the glycine site in the
      protection of the cells kept in an active state.

PMID- 9596558
TI  - Effect of lead on cytoskeletal proteins expressed in E14 mesencephalic primary
      cultures.
AB  - Several lines of evidence indicated that Pb exposure in vivo and in vitro altered
      neurite morphology in central and peripheral neurons. The present report shows
      that neurite length in mesencephalic primary cultures, consisting of neurons and
      glia, was decreased by Pb exposure when serum factors, presumably essential for
      glial functions, were absent in the culture medium. We studied whether a serum
      factor might control the mechanisms involved in the uptake and accumulation of Pb
      and its effect on cytoskeleton proteins. The total amount of Pb taken up in cell
      cultures was measured by atomic absorption spectroscopy and appeared to be down
      regulated by a non-albumin-like serum component. In presence of serum, Pb
      exposure failed to alter cytoskeletal proteins. Instead, in serum-free neurobasal
      medium, Pb uptake failed to reach saturation within 6 h. Western blot analysis
      showed that the tau, 280 kDa MAP-2b, 70 kDa MAP-2c and GAP-43 protein bands were
      decreased 24 h after a 3 h exposure to 3 or 6 microM Pb in absence of serum.
      However, if cultures were maintained in serum-containing media after a 3 h Pb
      exposure without serum, the immunoblots did not differ from those of controls. It
      can be inferred that a serum factor prevents cytoskeletal protein alterations by
      Pb. In serum free medium, Pb that is primarily scavenged by the metallothionein
      I/II isoforms present in glial cells, may bind to thiol residues of proteins
      involved in either oxidative stress response or transcriptional regulation of
      cytoskeletal proteins.

PMID- 9596559
TI  - Chemical modification of the dihydropyridines binding sites by lysine reagent,
      pyridoxal 5'-phosphate.
AB  - Treatment of rabbit brain membranes of the DHP binding sites of L-type Ca2+
      channel with lysine-specific reagent resulted in a time- and concentration
      dependent loss of [3H]nitrendipine binding activity. Following exposure to the
      maximum concentration of PLP (100 mM), [3H]nitrendipine binding was inhibited by
      up to 96.5%. Scatchard analysis of the binding data indicated that treatment with
      PLP resulted in a loss of [3H]nitrendipine binding sites with no effect on
      binding affinity. Considerable protection against PLP inactivation was obtained
      by nifedipine. These results indicate that lysine residue plays a critical role
      in maintaining the DHP-binding sites in a conformation capable of ligand binding.

PMID- 9596560
TI  - Detection of a decarboxylated dimer of aminoethylcysteine ketimine in bovine
      cerebellum.
AB  - Aminoethylcysteine ketimine is a sulfur-containing cyclic compound produced by
      the enzymatic alpha-deamination of the parent aminoethylcysteine that has been
      detected in bovine brain and cerebellum. Aminoethylcysteine ketimine is known to
      dimerize spontaneously and easily lose one carboxyl group. This decarboxylated
      compound, simply named the dimer, has been recently detected in normal human
      urine. In this article we provide evidence on the occurrence of the dimer in the
      bovine cerebellum.

PMID- 9596561
TI  - Endotoxin and intracerebroventricular injection of IL-1 and IL-6 induce rat brain
      metallothionein-I and -II.
AB  - Metallothioneins (MTs) are a family of proteins which in mammals is comprised of
      four isoforms (MT-I-IV). MT-I and MT-II are expressed in many tissues, whereas MT
      III is expressed exclusively in the central nervous system (CNS). In contrast to
      the liver, the knowledge of the regulation of the different MT isoforms in the
      brain is scarce. A number of cytokines have been shown to be important regulators
      of MT synthesis in vivo and in vitro. In accordance with this concept, the i.p.
      administration of endotoxin, which elicits the release of cytokines not only in
      peripheral tissues but also in the brain, caused an overall increase of MT-I + II
      levels in the rat brain which was very significant in medulla + pons and
      cerebellum. Among the putative cytokines involved in endotoxin-elicited brain MT
      I+II induction, interleukin-1 (IL-1) and interleukin-6 (IL-6) are likely
      candidates. These cytokines have a variety of effects in the brain, and they are
      major regulators of MT-I+II synthesis in tissues such as the liver. Here we show
      the administration of IL-1 and IL-6 into the third ventricle increased MT-I+II
      protein levels in specific brain areas in the rat. IL-1 tended to increase MT
      I+II levels in all brain areas studied, but significantly in the striatum,
      hypothalamus, medulla + pons and cerebellum. The effect of IL-6 was more
      restricted, but a significant increase of MT-I+II levels was still observed in
      frontal cortex, hypothalamus and cerebellum. The results suggest that IL-1 and IL
      6 are important regulators of brain MT-I+II and that these cytokines could
      mediate MT-I+II induction after an immunological insult.

PMID- 9596562
TI  - Expression of GABA(A) receptor isoform genes in the cerebral cortex of cirrhotic
      and alcoholic cases assessed by S1 nuclease protection assays.
AB  - Pathogenic processes underlying the localized reduction in neuronal number in
      cerebral cortex in human alcoholics have been reported to be associated with
      selective variations in the parameters of GABA(A) receptor site binding. Since
      the properties of the receptor complex depend on its isoform composition, we
      studied how the expression of GABA(A) receptor subunit isoform genes varied with
      alcoholism. Cerebral cortex tissue was obtained at autopsy from chronic human
      alcoholics (average ethanol intake > 80 g/day for most of their adult lives; n =
      17) and matched controls (< 20 g/day ethanol; n = 15). Eight of the alcoholics
      and five of the controls had pathologically confirmed cirrhosis of the liver.
      Expression of alpha1, alpha2, alpha3, alpha5, beta1, beta3, and gamma2 GABA(A)
      mRNA was assessed by S1 nuclease protection assays. After phosphorimager
      quantitation and normalization to GAPDH mRNA and 18S rRNA, none of the mRNA
      species showed significantly different expression in uncomplicated alcoholics.
      Analysis of differences in the patterns of expression of the various subunits
      showed the alpha1 signal was strongest in combined cirrhotic motor cortex while
      the alpha3 and beta3 values were greatest in combined cirrhotic frontal cortex.
      It appears that only major differences in mRNA expression may be detected by this
      technique in human brain.

PMID- 9596564
TI  - Imaging the deep seismic structure beneath a mid-ocean ridge: the MELT experiment
AB  - The Mantle Electromagnetic and Tomography (MELT) Experiment was designed to
      distinguish between competing models of magma generation beneath mid-ocean
      ridges. Seismological observations demonstrate that basaltic melt is present
      beneath the East Pacific Rise spreading center in a broad region several hundred
      kilometers across and extending to depths greater than 100 kilometers, not just
      in a narrow region of high melt concentration beneath the spreading center, as
      predicted by some models. The structure of the ridge system is strongly
      asymmetric: mantle densities and seismic velocities are lower and seismic
      anisotropy is stronger to the west of the rise axis.

PMID- 9596563
TI  - Culture medium components modulate retina cell damage induced by glutamate,
      kainate or "chemical ischemia".
AB  - The aim of this study was to determine whether culture-conditioned medium (CCM)
      can prevent neuronal damage caused by excitotoxicity or by "chemical ischemia" in
      cultured chick retina cells. Excitotoxic conditions were obtained by incubating
      retina cells with glutamate or kainate and "chemical ischemia" was induced by
      metabolic inhibition. In this case, cultures were briefly exposed to sodium
      cyanide, to block oxidative phosphorylation and iodoacetic acid, to block
      glycolysis. The assessment of neuronal injury was made spectrophotometrically by
      quantification of cellularly reduced MTT. Stimulation of retina cells with
      glutamate or kainate in serum deprived culture medium (BME-FCS), lead to a
      decrease in the MTT metabolism that was dependent on the time of exposure to the
      toxic agents. CCM prevented cell damage, either when present during the
      stimulation period or during the recovery period. This protection was more
      prominent in the case of kainate-induced neuronal death. "Chemical ischemia" also
      lead to a decrease of the MTT metabolism in a time-dependent manner and CCM
      protected retina cells from "ischemia"-induced lesions when present during the
      stimulation period and during the recovery period. The protective effect of CCM
      was partially decreased by the tyrosine kinase inhibitor, genistein, when the
      cells were stimulated with kainate, but not with glutamate, or when the cells
      were subjected to "chemical ischemia". CCM protected retina cells against both
      the acute and the delayed toxicity induced by either glutamate or kainate, or by
      "chemical ischemia", when present during both the insult and the recovery period.
      The presence of survival factors in the media may effectively inhibit the cell
      death signals generated by glutamate receptor activation or by "chemical
      ischemia".

PMID- 9596565
TI  - Off-axis crustal thickness across and along the east pacific rise within the MELT
      area 
AB  - Wide-angle seismic data along the Mantle Electromagnetic and Tomography (MELT)
      arrays show that the thickness of 0.5- to 1. 5-million-year-old crust of the
      Nazca Plate is not resolvably different from that of the Pacific Plate, despite
      an asymmetry in depth and gravity across this portion of the East Pacific Rise.
      Crustal thickness on similarly aged crust on the Nazca plate near a magmatically
      robust part of the East Pacific Rise at 17 degrees15'S is slightly thinner (5.1
      to 5.7 kilometers) than at the 15 degrees55'S overlapping spreading center (5.8
      to 6.3 kilometers). This small north-south off-axis crustal thickness difference
      may reflect along-axis temporal variations in magma supply, whereas the across
      axis asymmetry in depth and gravity must be caused by density variations in the
      underlying mantle.

PMID- 9596566
TI  - Shipboard geophysical indications of asymmetry and melt production beneath the
      east pacific rise near the MELT experiment 
AB  - Near the Mantle Electromagnetic and Tomography (MELT) Experiment, seamounts form
      and off-axis lava flows occur in a zone that extends farther to the west of the
      East Pacific Rise than to the east, indicating a broad, asymmetric region of melt
      production. More seamounts, slower subsidence, and less dense mantle on the
      western flank suggest transport of hotter mantle toward the axis from the west.
      Variations in axial ridge shape, axial magma chamber continuity, off-axis
      volcanism, and apparent mantle density indicate that upwelling is probably faster
      and more melt is produced beneath 17 degrees15'S than beneath 15 degrees55'S.
      Recent volcanism occurs above mantle with the lowest seismic velocities.

PMID- 9596567
TI  - Mantle seismic structure beneath the MELT region of the east pacific rise from P
      and S wave tomography 
AB  - Relative travel time delays of teleseismic P and S waves, recorded during the
      Mantle Electromagnetic and Tomography (MELT) Experiment, have been inverted
      tomographically for upper-mantle structure beneath the southern East Pacific
      Rise. A broad zone of low seismic velocities extends beneath the rise to depths
      of about 200 kilometers and is centered to the west of the spreading center. The
      magnitudes of the P and S wave anomalies require the presence of retained mantle
      melt; the melt fraction near the rise exceeds the fraction 300 kilometers off
      axis by as little as 1%. Seismic anisotropy, induced by mantle flow, is evident
      in the P wave delays at near-vertical incidence and is consistent with a half
      width of mantle upwelling of about 100 km.

PMID- 9596568
TI  - Structure of the upper mantle under the EPR from waveform inversion of regional
      events 
AB  - Waveform inversions of seismograms recorded at the Mantle Electromagnetic and
      Tomography (MELT) Experiment ocean bottom seismometer array from regional events
      with paths following the East Pacific Rise (EPR) require that low shear
      velocities (<3.7 km/s) extend to depths of more than 100 km below the rise axis.
      Velocities increase with average crustal age along ray paths. The reconciliation
      of Love and Rayleigh wave data requires that shear flow has aligned melt pockets
      or olivine crystals, creating an anisotropic uppermost mantle.

PMID- 9596569
TI  - Shear-wave splitting and implications for mantle flow beneath the MELT region of
      the east pacific rise 
AB  - Shear-wave splitting across the fast-spreading East Pacific Rise has been
      measured from records of SKS and SKKS phases on the ocean-bottom seismometers of
      the Mantle Electromagnetic and Tomography (MELT) Experiment. The direction of
      fast shear-wave polarization is aligned parallel to the spreading direction.
      Delay times between fast and slow shear waves are asymmetric across the rise, and
      off-axis values on the Pacific Plate are twice those on the Nazca Plate.
      Splitting on the Pacific Plate may reflect anisotropy associated with spreading
      induced flow above a depth of about 100 km, as well as a deeper contribution from
      warm asthenospheric return flow from the Pacific Superswell region.

PMID- 9596570
TI  - Mantle discontinuity structure beneath the southern east pacific rise from P-to-S
      converted phases 
AB  - Receiver functions derived from teleseismic body waves recorded by ocean-bottom
      seismometers on the southern East Pacific Rise reveal shear waves converted from
      compressional waves at the mantle discontinuities near 410- and 660-kilometer
      depth. The thickness of the mantle transition zone between the two
      discontinuities is normal relative to the global average and indicates that
      upwelling beneath the southern East Pacific Rise is not associated with an excess
      temperature in the mantle transition zone.

PMID- 9596571
TI  - Phase velocities of rayleigh waves in the MELT experiment on the east pacific
      rise 
AB  - The phase velocities of Rayleigh waves increase more rapidly with distance from
      the East Pacific Rise (EPR) axis than is predicted by models of conductive
      cooling of the lithosphere. Low velocities near the axis are probably caused by
      partial melt at depths of 20 to 70 kilometers in a zone several hundred
      kilometers wide. The lowest velocities are offset to the west of the EPR. Wave
      propagation is anisotropic; the fast direction is approximately perpendicular to
      the ridge, parallel to the spreading direction. Anisotropy increases from a
      minimum near the axis to 3 percent or more on the flanks.

PMID- 9596572
TI  - The radio-frequency single-electron transistor (RF-SET): A fast and
      ultrasensitive electrometer 
AB  - A new type of electrometer is described that uses a single-electron transistor
      (SET) and that allows large operating speeds and extremely high charge
      sensitivity. The SET readout was accomplished by measuring the damping of a 1.7
      gigahertz resonant circuit in which the device is embedded, and in some ways is
      the electrostatic "dual" of the well-known radio-frequency superconducting
      quantum interference device. The device is more than two orders of magnitude
      faster than previous single-electron devices, with a constant gain from dc to
      greater than 100 megahertz. For a still-unoptimized device, a charge sensitivity
      of 1.2 x 10(-5) e/hertz was obtained at a frequency of 1.1 megahertz, which is
      about an order of magnitude better than a typical, 1/f-noise-limited SET, and
      corresponds to an energy sensitivity (in joules per hertz) of about 41 Planck's
      over 2pi.

PMID- 9596574
TI  - Viscosity of oceanic asthenosphere inferred from remote triggering of earthquakes
AB  - A sequence of large interplate earthquakes from 1952 to 1965 along the Aleutian
      arc and Kurile-Kamchatka trench released accumulated stresses along nearly the
      entire northern portion of the Pacific Plate boundary. The postseismic stress
      evolution across the northern Pacific and Arctic basins, calculated from a
      viscoelastic coupling model with an asthenospheric viscosity of 5 x 10(17) pascal
      seconds, is consistent with triggering of oceanic intraplate earthquakes,
      temporal patterns in seismicity at remote plate boundaries, and space-based
      geodetic measurements of anomalous velocity over an area 7000 by 7000 kilometers
      square during the 30-year period after the sequence.

PMID- 9596573
TI  - Salts on Europa's surface detected by Galileo's near infrared mapping
      spectrometer. The NIMS Team.
AB  - Reflectance spectra in the 1- to 2.5-micrometer wavelength region of the surface
      of Europa obtained by Galileo's Near Infrared Mapping Spectrometer exhibit
      distorted water absorption bands that indicate the presence of hydrated minerals.
      The laboratory spectra of hydrated salt minerals such as magnesium sulfates and
      sodium carbonates and mixtures of these minerals provide a close match to the
      Europa spectra. The distorted bands are only observed in the optically darker
      areas of Europa, including the lineaments, and may represent evaporite deposits
      formed by water, rich in dissolved salts, reaching the surface from a water-rich
      layer underlying an ice crust.

PMID- 9596575
TI  - Geochemical evidence for a comet shower in the late Eocene.
AB  - Analyses of pelagic limestones indicate that the flux of extraterrestrial helium
      3 to Earth was increased for a 2.5-million year (My) period in the late Eocene.
      The enhancement began approximately 1 My before and ended approximately 1.5 My
      after the major impact events that produced the large Popigai and Chesapeake Bay
      craters approximately 36 million years ago. The correlation between increased
      concentrations of helium-3, a tracer of fine-grained interplanetary dust, and
      large impacts indicates that the abundance of Earth-crossing objects and
      dustiness in the inner solar system were simultaneously but only briefly
      enhanced. These observations provide evidence for a comet shower triggered by an
      impulsive perturbation of the Oort cloud.

PMID- 9596576
TI  - Fullerene pipes 
AB  - Single-wall fullerene nanotubes were converted from nearly endless, highly
      tangled ropes into short, open-ended pipes that behave as individual
      macromolecules. Raw nanotube material was purified in large batches, and the
      ropes were cut into 100- to 300-nanometer lengths. The resulting pieces formed a
      stable colloidal suspension in water with the help of surfactants. These
      suspensions permit a variety of manipulations, such as sorting by length,
      derivatization, and tethering to gold surfaces.

PMID- 9596577
TI  - Cloned transgenic calves produced from nonquiescent fetal fibroblasts.
AB  - An efficient system for genetic modification and large-scale cloning of cattle is
      of importance for agriculture, biotechnology, and human medicine. Here, actively
      dividing fetal fibroblasts were genetically modified with a marker gene, a clonal
      line was selected, and the cells were fused to enucleated mature oocytes. Out of
      28 embryos transferred to 11 recipient cows, three healthy, identical, transgenic
      calves were generated. Furthermore, the life-span of near senescent fibroblasts
      could be extended by nuclear transfer, as indicated by population doublings in
      fibroblast lines derived from a 40-day-old fetal clone. With the ability to
      extend the life-span of these primary cultured cells, this system would be useful
      for inducing complex genetic modifications in cattle.

PMID- 9596578
TI  - A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein
      phosphatase 2A.
AB  - Stimulation of T lymphocytes results in a rapid increase in intracellular calcium
      concentration ([Ca2+]i) that parallels the activation of Ca2+-calmodulin
      dependent protein kinase IV (CaMKIV), a nuclear enzyme that can phosphorylate and
      activate the cyclic adenosine monophosphate (cAMP) response element-binding
      protein (CREB). However, inactivation of CaMKIV occurs despite the sustained
      increase in [Ca2+]i that is required for T cell activation. A stable and
      stoichiometric complex of CaMKIV with protein serine-threonine phosphatase 2A
      (PP2A) was identified in which PP2A dephosphorylates CaMKIV and functions as a
      negative regulator of CaMKIV signaling. In Jurkat T cells, inhibition of PP2A
      activity by small t antigen enhanced activation of CREB-mediated transcription by
      CaMKIV. These findings reveal an intracellular signaling mechanism whereby a
      protein serine-threonine kinase (CaMKIV) is regulated by a tightly associated
      protein serine-threonine phosphatase (PP2A).

PMID- 9596579
TI  - Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein
      kinase.
AB  - MAP kinase phosphatase-3 (MKP-3) dephosphorylates phosphotyrosine and
      phosphothreonine and inactivates selectively ERK family mitogen-activated protein
      (MAP) kinases. MKP-3 was activated by direct binding to purified ERK2. Activation
      was independent of protein kinase activity and required binding of ERK2 to the
      noncatalytic amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker
      ERK2 mutant D319N nor c-Jun amino-terminal kinase-stress-activated protein kinase
      (JNK/SAPK) or p38 MAP kinases bound MKP-3 or caused its catalytic activation.
      These kinases were also resistant to enzymatic inactivation by MKP-3. Another
      homologous but nonselective phosphatase, MKP-4, bound and was activated by ERK2,
      JNK/SAPK, and p38 MAP kinases. Catalytic activation of MAP kinase phosphatases
      through substrate binding may regulate MAP kinase activation by a large number of
      receptor systems.

PMID- 9596580
TI  - Requirement for gammadelta T cells in allergic airway inflammation.
AB  - The factors that contribute to allergic asthma are unclear but the resulting
      condition is considered a consequence of a type-2 T helper (TH2) cell response.
      In a model of pulmonary allergic inflammation, mice that lacked gammadelta T
      cells had decreases in specific immunoglobulin E (IgE) and IgG1 and pulmonary
      interleukin-5 (IL-5) release as well as in eosinophil and T cell infiltration
      compared with wild-type mice. These responses were restored by administration of
      IL-4 to gammadelta T cell-deficient mice during the primary immunization. Thus,
      gammadelta T cells are essential for inducing IL-4-dependent IgE and IgG1
      responses and for TH2-mediated airway inflammation to peptidic antigens.

PMID- 9596581
TI  - Aspirin-like molecules that covalently inactivate cyclooxygenase-2.
AB  - Many of aspirin's therapeutic effects arise from its acetylation of
      cyclooxygenase-2 (COX-2), whereas its antithrombotic and ulcerogenic effects
      result from its acetylation of COX-1. Here, aspirin-like molecules were designed
      that preferentially acetylate and irreversibly inactivate COX-2. The most potent
      of these compounds was o-(acetoxyphenyl)hept-2-ynyl sulfide (APHS). Relative to
      aspirin, APHS was 60 times as reactive against COX-2 and 100 times as selective
      for its inhibition; it also inhibited COX-2 in cultured macrophages and colon
      cancer cells and in the rat air pouch in vivo. Such compounds may lead to the
      development of aspirin-like drugs for the treatment or prevention of
      immunological and proliferative diseases without gastrointestinal or hematologic
      side effects.

PMID- 9596582
TI  - Molecular basis for interactions of G protein betagamma subunits with effectors.
AB  - Both the alpha and betagamma subunits of heterotrimeric guanine nucleotide
      binding proteins (G proteins) communicate signals from receptors to effectors.
      Gbetagamma subunits can regulate a diverse array of effectors, including ion
      channels and enzymes. Galpha subunits bound to guanine diphosphate (Galpha-GDP)
      inhibit signal transduction through Gbetagamma subunits, suggesting a common
      interface on Gbetagamma subunits for Galpha binding and effector interaction. The
      molecular basis for interaction of Gbetagamma with effectors was characterized by
      mutational analysis of Gbeta residues that make contact with Galpha-GDP. Analysis
      of the ability of these mutants to regulate the activity of calcium and potassium
      channels, adenylyl cyclase 2, phospholipase C-beta2, and beta-adrenergic receptor
      kinase revealed the Gbeta residues required for activation of each effector and
      provides evidence for partially overlapping domains on Gbeta for regulation of
      these effectors. This organization of interaction regions on Gbeta for different
      effectors and Galpha explains why subunit dissociation is crucial for signal
      transmission through Gbetagamma subunits.

PMID- 9596583
TI  - Distinct WNT pathways regulating AER formation and dorsoventral polarity in the
      chick limb bud.
AB  - The apical ectodermal ridge (AER) is an essential structure for vertebrate limb
      development. Wnt3a is expressed during the induction of the chick AER, and
      misexpression of Wnt3a induces ectopic expression of AER-specific genes in the
      limb ectoderm. The genes beta-catenin and Lef1 can mimic the effect of Wnt3a, and
      blocking the intrinsic Lef1 activity disrupts AER formation. Hence, Wnt3a
      functions in AER formation through the beta-catenin/LEF1 pathway. In contrast,
      neither beta-catenin nor Lef1 affects the Wnt7a-regulated dorsoventral polarity
      of the limb. Thus, two related Wnt genes elicit distinct responses in the same
      tissues by using different intracellular pathways.

PMID- 9596584
TI  - X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor
      2.
AB  - Activation and covalent attachment of complement component C3 to pathogens is the
      key step in complement-mediated host defense. Additionally, the antigen-bound C3d
      fragment interacts with complement receptor 2 (CR2; also known as CD21) on B
      cells and thereby contributes to the initiation of an acquired humoral response.
      The x-ray crystal structure of human C3d solved at 2.0 angstroms resolution
      reveals an alpha-alpha barrel with the residues responsible for thioester
      formation and covalent attachment at one end and an acidic pocket at the other.
      The structure supports a model whereby the transition of native C3 to its
      functionally active state involves the disruption of a complementary domain
      interface and provides insight into the basis for the interaction between C3d and
      CR2.

PMID- 9596585
TI  - The importance of parenting in child health. Doctors as well as the government
      should do more to support parents.

PMID- 9596586
TI  - Diagnosing and treating chesty infants. A short trial of inhaled corticosteroid
      is probably the best approach.

PMID- 9596587
TI  - Provision of intensive care for children. A geographically integrated service may
      now be achieved.

PMID- 9596588
TI  - Breast feeding: the baby friendly initiative. Must adapt and develop to succeed.

PMID- 9596589
TI  - Protecting children from armed conflict. The UN convention needs an enforcing
      arm.

PMID- 9596590
TI  - Violence begins at home. Domestic strife has lifelong effects on children.

PMID- 9596591
TI  - Pain relief in children. Doing the simple things better.

PMID- 9596592
TI  - Systematic review of efficacy of cognitive behaviour therapies in childhood and
      adolescent depressive disorder.
AB  - OBJECTIVE: To determine whether cognitive behaviour therapy is an effective
      treatment for childhood and adolescent depressive disorder. DESIGN: Systematic
      review of six randomised trials comparing the efficacy of cognitive behaviour
      therapy with inactive interventions in subjects aged 8 to 19 years with
      depressive disorder. MAIN OUTCOME MEASURE: Remission from depressive disorder.
      RESULTS: The rate of remission from depressive disorder was higher in the therapy
      group (129/208; 62%) than in the comparison group (61/168; 36%). The pooled odds
      ratio was 3.2 (95% confidence interval 1.9 to 5.2), suggesting a significant
      benefit of active treatment. Most studies, however, were based on relatively mild
      cases of depression and were of only moderate quality. CONCLUSIONS: Cognitive
      behaviour therapy may be of benefit for depressive disorder of moderate severity
      in children and adolescents. It cannot, however, yet be recommended for severe
      depression. Definitive large trials will be required to determine whether the
      results of this systematic review are reliable.

PMID- 9596594
TI  - Initiatives to improve childhood immunisation uptake: a randomised controlled
      trial.

PMID- 9596593
TI  - Effectiveness of treatments for infantile colic: systematic review.
AB  - OBJECTIVE: To evaluate the effectiveness of diets, drug treatment, and
      behavioural interventions on infantile colic in trials with crying or the
      presence of colic as the primary outcome measure. DATA SOURCES: Controlled
      clinical trials identified by a highly sensitive search strategy in Medline (1966
      96), Embase (1986-95), and the Cochrane Controlled Trials Register, in
      combination with reference checking for further relevant publications. Keywords
      were crying and colic. STUDY SELECTION: Two independent assessors selected
      controlled trials with interventions lasting at least 3 days that included
      infants younger than 6 months who cried excessively. DATA SYNTHESIS:
      Methodological quality was assessed by two assessors independently with a quality
      assessment scale (range 0-5). Effect sizes were calculated as percentage success.
      Effect sizes of trials using identical interventions were pooled using a random
      effects model. RESULTS: 27 controlled trials were identified. Elimination of
      cows' milk protein was effective when substituted by hypoallergenic formula milks
      (effect size 0.22 (95% confidence interval 0.09 to 0.34)). The effectiveness of
      substitution by soy formula milks was unclear when only trials of good
      methodological quality were considered. The benefit of eliminating cows' milk
      protein was not restricted to highly selected populations. Dicyclomine was
      effective (effect size 0.46 (0.33 to 0.60)), but serious side effects have been
      reported. The advice to reduce stimulation was beneficial (effect size 0.48 (0.23
      to 0.74)), whereas the advice to increase carrying and holding seemed not to
      reduce crying. No benefit was shown for simethicone. Uncertainty remained about
      the effectiveness of low lactose formula milks. CONCLUSIONS: Infantile colic
      should preferably be treated by advising carers to reduce stimulation and with a
      one week trial of a hypoallergenic formula milk.

PMID- 9596596
TI  - Science commentary: why conjugate vaccines protect longer 

PMID- 9596595
TI  - Immunological response to conjugate vaccines in infants: follow up study.

PMID- 9596597
TI  - Morbidity and healthcare utilisation of children in households with one adult:
      comparative observational study.
AB  - OBJECTIVE: To identify and consider differences in morbidity in children in
      households with one adult presenting to general practitioners compared with
      children in households with more than one adult. DESIGN: Observational study;
      data analysed with logistic regression controlling for age, sex, and practice.
      SUBJECTS: 93 356 children aged 0-15 years included in the fourth national study
      of morbidity in general practice and for whom data about household structure were
      available. Among them 10 983 (11.8%) were living in households with a sole adult.
      METHODS: Morbidity data were recorded from each consultation as the assessment
      diagnosis made by the general practitioner. MAIN OUTCOME MEASURES: Number of
      consultations and consultations per person for any illness, infections, acute
      respiratory infections, asthma, and accidents; number presenting and mean
      consultations per person for immunisation; number receiving home visits and home
      visits per person visited; average annual frequency of consultation among those
      consulting. RESULTS: Compared with children in other households, a higher
      proportion of children in households with one adult consulted for infections and
      accidents. The proportion consulting for immunisation was lower and the
      proportion receiving home visits greater. Mean numbers of consultations per
      person consulting were also generally higher for all conditions. For infections,
      accidents, and home visits, the differences were evident in all age groups.
      CONCLUSIONS: The study confirms the importance of single parent families as an
      indicator of deprivation. Children in such families should be targeted for
      immunisation and accident prevention.

PMID- 9596598
TI  - A randomised controlled trial of general practitioner safety advice for families
      with children under 5 years.
AB  - OBJECTIVE: To assess effectiveness of general practitioner advice about child
      safety, and provision of low cost safety equipment to low income families, on use
      of safety equipment and safe practices at home. DESIGN: Randomised, unblinded,
      controlled trial with initial assessment and six week follow up by telephone
      survey. Twenty families from intervention and control groups were randomly
      selected for a home visit to assess validity of responses to second survey.
      SETTING: A general practice in Nottingham. SUBJECTS: 98% (165/169) of families
      with children aged under 5 years registered with the practice. INTERVENTIONS:
      General practitioner safety advice plus, for families receiving means tested
      state benefits, access to safety equipment at low cost. Control families received
      usual care. MAIN OUTCOME MEASURES: Possession and use of safety equipment and
      safe practices at home. RESULTS: Before intervention, the two groups differed
      only in possession of fireguards. After intervention, significantly more families
      in intervention group used fireguards (relative risk 1.89, 95% confidence
      interval 1.18 to 2.94), smoke alarms (1.14, 1.04 to 1.25), socket covers (1.27,
      1.10 to 1.48), locks on cupboards for storing cleaning materials (1.38, 1.02 to
      1.88), and door slam devices (3.60, 2.17 to 5.97). Also, significantly more
      families in intervention group showed very safe practice in storage of sharp
      objects (1.98, 1.38 to 2.83), storage of medicines (1.15, 1.03 to 1.28), window
      safety (1.30, 1.06 to 1.58), fireplace safety (1.84, 1.34 to 2.54), socket safety
      (1.77, 1.37 to 2.28), smoke alarm safety (1.11, 1.01 to 1.22), and door slam
      safety (7.00, 3.15 to 15.6). Stratifying results by receipt of state benefits
      showed that intervention was at least as effective in families receiving benefits
      as others. CONCLUSIONS: General practitioner advice, coupled with access to low
      cost equipment for low income families, increased use of safety equipment and
      other safe practices. These findings are encouraging for provision of injury
      prevention in primary care.

PMID- 9596599
TI  - Fetal medicine.

PMID- 9596600
TI  - Allergy in general practice.

PMID- 9596601
TI  - Children and the inverse care law.

PMID- 9596602
TI  - Administration of medicines in school: who is responsible?

PMID- 9596603
TI  - Personal paper: attention deficit hyperactivity disorder is underdiagnosed and
      undertreated in Britain.

PMID- 9596604
TI  - Street children in Latin America.

PMID- 9596605
TI  - Children as consumers.

PMID- 9596606
TI  - Concerns about using and interpreting covert video surveillance.

PMID- 9596607
TI  - Smoking should be mentioned as cause of death on death certificates.

PMID- 9596609
TI  - Octreotide for cirrhosis after variceal bleeding. Authors' claims for octreotide
      were not justified.

PMID- 9596608
TI  - Intermittent low dose prednisolone is safe in rheumatoid arthritis.

PMID- 9596610
TI  - Are the media manipulating the GMC?

PMID- 9596611
TI  - Consent may be hard to obtain for incompetent patients when relatives object.

PMID- 9596612
TI  - Foot morbidity and exposure to chiropody. Purchasers still need to decide about
      investing in foot health care.

PMID- 9596613
TI  - General practitioners' self assessment of knowledge. The vast range of clinical
      conditions means that doctors cannot know everything.

PMID- 9596614
TI  - Preventing RhD haemolytic disease of the newborn. Revised guidelines advocate two
      doses of anti-D immunoglobulin for antenatal prophylaxis.

PMID- 9596615
TI  - Mortality and distribution of income. Societies with narrower income
      distributions are healthier.

PMID- 9596617
TI  - BMA council agrees structure for devolution 

PMID- 9596616
TI  - William lees price 

PMID- 9596618
TI  - The other side 

PMID- 9596619
TI  - Children have feelings too 

PMID- 9596621
TI  - Cognitive behaviour therapy is promising in childhood depressive disorder 

PMID- 9596620
TI  - Di Bella's miracle method 

PMID- 9596622
TI  - Avoidance of cows' milk is effective in infantile colic 

PMID- 9596623
TI  - Conjugate hib vaccines given in infancy without booster doses may produce long
      term protection 

PMID- 9596624
TI  - District-wide initiatives to improve immunisation uptake don't work 

PMID- 9596625
TI  - Children of single parents have more accidents, more home visits, and less
      immunisation 

PMID- 9596626
TI  - GPs giving advice on child safety is effective 

PMID- 9596627
TI  - Small nucleolar RNAs and pre-rRNA processing in plants.

PMID- 9596628
TI  - Rhizobium nod factor signaling. Evidence for a g protein-mediated transduction
      mechanism 
AB  - Rhizobium nodulation (Nod) factors are lipochitooligosaccharide signals that
      elicit key symbiotic developmental responses in the host legume root. In this
      study, we have investigated Nod factor signal transduction in the Medicago root
      epidermis by using a pharmacological approach in conjunction with transgenic
      plants expressing the Nod factor-responsive reporter construct pMtENOD12-GUS.
      Evidence for the participation of heterotrimeric G proteins in Nod factor
      signaling has come from three complementary observations: (1) the amphiphilic
      peptides mastoparan and Mas7, known G protein agonists, are able to mimic Nod
      factor-induced epidermal MtENOD12 expression; (2) growth of plants in nodulation
      inhibiting conditions (10 mM NH4NO3) leads to a dramatic reduction in both Nod
      factor- and mastoparan-elicited gene expression; and (3) bacterial pertussis
      toxin, a well-characterized G protein antagonist, blocks the activities of both
      the Nod factor and mastoparan. In addition, we have found that antagonists that
      interfere with phospholipase C activity (neomycin and U73122) and Ca2+
      influx/release (EGTA, La3+, and ruthenium red) block Nod factor/mastoparan
      activity. Taken together, these results are consistent with a Nod factor signal
      transduction mechanism involving G protein mediation coupled to the activation of
      both phosphoinositide and Ca2+ second messenger pathways.

PMID- 9596629
TI  - Arabidopsis bZIP protein HY5 directly interacts with light-responsive promoters
      in mediating light control of gene expression.
AB  - The Arabidopsis HY5 gene has been defined genetically as a positive regulator of
      photomorphogenesis and recently has been shown to encode a basic leucine zipper
      type of transcription factor. Here, we report that HY5 is constitutively nuclear
      localized and is involved in light regulation of transcriptional activity of the
      promoters containing the G-box, a well-characterized light-responsive element
      (LRE). In vitro DNA binding studies suggested that HY5 can bind specifically to
      the G-box DNA sequences but not to any of the other LREs present in the light
      responsive promoters examined. High-irradiance light activation of two synthetic
      promoters containing either the consensus G-box alone or the G-box combined with
      the GATA motif (another LRE) and the native Arabidopsis ribulose bisphosphate
      carboxylase small subunit gene RBCS-1A promoter, which has an essential copy of
      the G-box, was significantly compromised in the hy5 mutant. The hy5 mutation's
      effect on the high-irradiance light activation of gene expression was observed in
      both photosynthetic and nonphotosynthetic tissues. Furthermore, the
      characteristic phytochrome-mediated red light- and far-red light-reversible low
      fluence induction of the G-box-containing promoters was diminished specifically
      in hy5 plants. These results suggest that HY5 may interact directly with the G
      box in the promoters of light-inducible genes to mediate light-controlled
      transcriptional activity.

PMID- 9596630
TI  - Barley aleurone cells contain two types of vacuoles. Characterization Of lytic
      organelles by use of fluorescent probes 
AB  - Light microscopy was used to study the structure and function of vacuoles in
      living protoplasts of barley (Hordeum vulgare cv Himalaya) aleurone. Light
      microscopy showed that aleurone protoplasts contain two distinct types of
      vacuole: the protein storage vacuole and a lysosome-like organelle, which we have
      called the secondary vacuole. Fluorescence microscopy using pH-sensitive
      fluorescent probes and a fluorogenic substrate for cysteine proteases showed that
      both protein storage vacuoles and secondary vacuoles are acidic, lytic
      organelles. Ratio imaging showed that the pH of secondary vacuoles was lower in
      aleurone protoplasts incubated in gibberellic acid than in those incubated in
      abscisic acid. Uptake of fluorescent probes into intact, isolated protein storage
      vacuoles and secondary vacuoles required ATP and occurred via at least two types
      of vanadate-sensitive, ATP-dependent tonoplast transporters. One transporter
      catalyzed the accumulation of glutathione-conjugated probes, and another
      transported probes not conjugated to glutathione.

PMID- 9596631
TI  - Chloroplast development at low temperatures requires a homolog of DIM1, a yeast
      gene encoding the 18S rRNA dimethylase.
AB  - Poikilothermic organisms require mechanisms that allow survival at chilling
      temperatures (2 to 15 degreesC). We have isolated chilling-sensitive mutants of
      Arabidopsis, a plant that is very chilling resistant, and are characterizing them
      to understand the genes involved in chilling resistance. The T-DNA-tagged mutant
      paleface1 (pfc1) grows normally at 22 degrees C but at 5 degrees C exhibits a
      pattern of chilling-induced chlorosis consistent with a disruption of chloroplast
      development. Genomic DNA flanking the T-DNA was cloned and used to isolate wild
      type genomic and cDNA clones. The PFC1 transcript is present at a low level in
      wild-type plants and was not detected in pfc1 plants. Wild-type Arabidopsis
      expressing antisense constructs of PFC1 grew normally at 22 degrees C but showed
      chilling-induced chlorosis, confirming that the gene is essential for low
      temperature development of chloroplasts. The deduced amino acid sequence of PFC1
      has identity with rRNA methylases found in bacteria and yeast that modify
      specific adenosines of pre-rRNA transcripts. The pfc1 mutant does not have these
      modifications in the small subunit rRNA of the plastid.

PMID- 9596632
TI  - Engineering secondary metabolism in maize cells by ectopic expression of
      transcription factors.
AB  - Manipulation of plant natural product biosynthesis through genetic engineering is
      an attractive but technically challenging goal. Here, we demonstrate that
      different secondary metabolites can be produced in cultured maize cells by
      ectopic expression of the appropriate regulatory genes. Cell lines engineered to
      express the maize transcriptional activators C1 and R accumulate two cyanidin
      derivatives, which are similar to the predominant anthocyanin found in
      differentiated plant tissues. In contrast, cell lines that express P accumulate
      various 3-deoxy flavonoids. Unexpectedly, P-expressing cells in culture also
      accumulate phenylpropanoids and green fluorescent compounds that are targeted to
      different subcellular compartments. Two endogenous biosynthetic genes (c2 and a1,
      encoding chalcone synthase and flavanone/dihydroflavonol reductase, respectively)
      are independently activated by ectopic expression of either P or C1/R, and there
      is a dose-response relationship between the transcript level of P and the degree
      to which c2 or a1 is expressed. Our results support a simple model showing how
      the gene encoding P may act as a quantitative trait locus controlling
      insecticidal C-glycosyl flavone level in maize silks, and they suggest how p1
      might confer a selective advantage against insect predation in maize.

PMID- 9596633
TI  - Arabidopsis gls mutants and distinct Fd-GOGAT genes. Implications for
      photorespiration and primary nitrogen assimilation.
AB  - Ferredoxin-dependent glutamate synthase (Fd-GOGAT) plays a major role in
      photorespiration in Arabidopsis, as has been determined by the characterization
      of mutants deficient in Fd-GOGAT enzyme activity (gls). Despite genetic evidence
      for a single Fd-GOGAT locus and gene, we discovered that Arabidopsis contains two
      expressed genes for Fd-GOGAT (GLU1 and GLU2). Physical and genetic mapping of the
      gls1 locus and GLU genes indicates that GLU1 is linked to the gls1 locus, whereas
      GLU2 maps to a different chromosome. Contrasting patterns of GLU1 and GLU2
      expression explain why a mutation in only one of the two genes for Fd-GOGAT leads
      to a photorespiratory phenotype in the gls1 mutants. GLU1 mRNA was expressed at
      the highest levels in leaves, and its mRNA levels were specifically induced by
      light or sucrose. In contrast, GLU2 mRNA was expressed at lower constitutive
      levels in leaves and preferentially accumulated in roots. Although these results
      suggest a major role for GLU1 in photorespiration, the sucrose induction of GLU1
      mRNA in leaves also suggests a role in primary nitrogen assimilation. This
      possibility is supported by the finding that chlorophyll levels of a gls mutant
      are significantly lower than those of the wild type when grown under conditions
      that suppress photorespiration. Both the mutant analysis and gene regulation
      studies suggest that GLU1 plays a major role in photorespiration and also plays a
      role in primary nitrogen assimilation in leaves, whereas the GLU2 gene may play a
      major role in primary nitrogen assimilation in roots.

PMID- 9596634
TI  - Regulation of cell-specific inositol metabolism and transport in plant salinity
      tolerance.
AB  - myo-Inositol and its derivatives are commonly studied with respect to cell
      signaling and membrane biogenesis, but they also participate in responses to
      salinity in animals and plants. In this study, we focused on L-myo-inositol 1
      phosphate synthase (INPS), which commits carbon to de novo synthesis, and myo
      inositol O-methyltransferase (IMT), which uses myo-inositol for stress-induced
      accumulation of a methylinositol, D-ononitol. The Imt and Inps promoters are
      transcriptionally controlled. We determined that the transcription rates,
      transcript levels, and protein abundance are correlated. During normal growth,
      INPS is present in all cells, but IMT is repressed. After salinity stress, the
      amount of INPS was enhanced in leaves but repressed in roots. IMT was induced in
      all cell types. The absence of myo-inositol synthesis in roots is compensated by
      inositol/ononitol transport in the phloem. The mobilization of photosynthate
      through myo-inositol translocation links root metabolism to photosynthesis. Our
      model integrates the transcriptional control of a specialized metabolic pathway
      with physiological reactions in different tissues. The tissue-specific
      differential regulation of INPS, which leads to a gradient of myo-inositol
      synthesis, supports root growth and sodium uptake. By inducing expression of IMT
      and increasing myo-inositol synthesis, metabolic end products accumulate,
      facilitating sodium sequestration and protecting photosynthesis.

PMID- 9596635
TI  - Xa21D encodes a receptor-like molecule with a leucine-rich repeat domain that
      determines race-specific recognition and is subject to adaptive evolution.
AB  - The rice Xa21 gene confers resistance to Xanthomonas oryzae pv oryzae in a race
      specific manner. Analysis of the inheritance patterns and resistance spectra of
      transgenic plants carrying six Xa21 gene family members indicated that one
      member, designated Xa21D, displayed a resistance spectrum identical to that
      observed for Xa21 but conferred only partial resistance. Xa21D encodes a receptor
      like protein carrying leucine-rich repeat (LRR) motifs in the presumed
      extracellular domain. The Xa21D transcript terminates shortly after the stop
      codon introduced by the retrotransposon Retrofit. Comparison of nucleotide
      substitutions in the LRR coding regions of Xa21 and Xa21D provided evidence of
      adaptive selection. Both functional and evolutionary evidence indicates that the
      Xa21D LRR domain controls race-specific pathogen recognition.

PMID- 9596636
TI  - The sex-inducing pheromone and wounding trigger the same set of genes in the
      multicellular green alga Volvox.
AB  - The sex-inducing pheromone of the multicellular green alga Volvox carteri is a
      glycoprotein that triggers development of males and females at a concentration
      <10(-16) M. By differential screening of a cDNA library, two novel genes were
      identified that are transcribed under the control of this pheromone.
      Unexpectedly, one gene product was characterized as a lysozyme/chitinase, and the
      other gene product was shown to encode a polypeptide with a striking modular
      composition. This polypeptide has a cysteine protease domain separated by an
      extensin-like module from three repeats of a chitin binding domain. In higher
      plants, similar protein families are known to play an important role in defense
      against fungi. Indeed, we found that the same set of genes triggered by the
      sexual pheromone was also inducible in V. carteri by wounding.

PMID- 9596637
TI  - Gibberellins promote flowering of arabidopsis by activating the LEAFY promoter 
AB  - The gibberellin class of plant hormones has been implicated in the control of
      flowering in several species. In Arabidopsis, severe reduction of endogenous
      gibberellins delays flowering in long days and prevents flowering in short days.
      We have investigated how the differential effects of gibberellins on flowering
      correlate with expression of LEAFY, a floral meristem identity gene. We have
      found that the failure of gibberellin-deficient ga1-3 mutants to flower in short
      days was paralleled by the absence of LEAFY promoter induction. A causal
      connection between these two events was confirmed by the ability of a
      constitutively expressed LEAFY transgene to restore flowering to ga1-3 mutants in
      short days. In contrast to short days, impairment of gibberellin biosynthesis
      caused merely a reduction of LEAFY expression when plants were grown in long days
      or with sucrose in the dark. As a first step toward identifying other small
      molecules that might regulate flowering, we have developed a rapid in vitro assay
      for LEAFY promoter activity.

PMID- 9596638
TI  - Comparative mapping of the Brassica S locus region and its homeolog in
      Arabidopsis. Implications for the evolution of mating systems in the
      Brassicaceae.
AB  - The crucifer family includes self-incompatible genera, such as Brassica, and self
      fertile genera, such as Arabidopsis. To gain insight into mechanisms underlying
      the evolution of mating systems in this family, we used a selective comparative
      mapping approach between Brassica campestris plants homozygous for the S8
      haplotype and Arabidopsis. Starting with markers flanking the self
      incompatibility genes in Brassica, we identified the homeologous region in
      Arabidopsis as a previously uncharacterized segment of chromosome 1 in the
      immediate vicinity of the ethylene response gene ETR1. A total of 26 genomic and
      21 cDNA markers derived from Arabidopsis yeast artificial and bacterial
      artificial chromosome clones were used to analyze this region in the two genomes.
      Approximately half of the cDNAs isolated from the region represent novel
      expressed sequence tags that do not match entries in the DNA and protein
      databases. The physical maps that we derived by using these markers as well as
      markers isolated from bacteriophage clones spanning the S8 haplotype revealed a
      high degree of synteny at the submegabase scale between the two homeologous
      regions. However, no sequences similar to the Brassica S locus genes that are
      known to be required for the self-incompatibility response were detected within
      this interval or other regions of the Arabidopsis genome. This observation is
      consistent with deletion of self-recognition genes as a mechanism for the
      evolution of autogamy in the Arabidopsis lineage.

PMID- 9596639
TI  - BiP and calreticulin form an abundant complex that is independent of endoplasmic
      reticulum stress 
AB  - BiP is found in association with calreticulin, both in the presence and absence
      of endoplasmic reticulum stress. Although the BiP-calreticulin complex can be
      disrupted by ATP, several properties suggest that the calreticulin associated
      with BiP is neither unfolded nor partially or improperly folded. (1) The complex
      is stable in vivo and does not dissociate during 8 hr of chase. (2) When present
      in the complex, calreticulin masks epitopes at the C terminus of BiP that are not
      masked when BiP is bound to an assembly-defective protein. And (3) overproduction
      of calreticulin does not lead to the recruitment of more BiP into complexes with
      calreticulin. The BiP-calreticulin complex can be disrupted by low pH but not by
      divalent cation chelators. When the endoplasmic reticulum retention signal of BiP
      is removed, complex formation with calreticulin still occurs, and this explains
      the poor secretion of the truncated molecule. Gel filtration experiments showed
      that BiP and calreticulin are present in distinct high molecular weight complexes
      in which both molecules interact with each other. The possible functions of this
      complex are discussed.

PMID- 9596640
TI  - Transport of storage proteins to protein storage vacuoles is mediated by large
      precursor-accumulating vesicles 
AB  - Novel vesicles that accumulate large amounts of proprotein precursors of storage
      proteins were purified from maturing pumpkin seeds. These vesicles were
      designated precursor-accumulating (PAC) vesicles and had diameters of 200 to 400
      nm. They contained an electron-dense core of storage proteins surrounded by an
      electron-translucent layer, and some vesicles also contained small vesicle-like
      structures. Immunocytochemical analysis revealed numerous electron-dense
      aggregates of storage proteins within the endoplasmic reticulum. It is likely
      that these aggregates develop into the electron-dense cores of the PAC vesicles
      and then leave the endoplasmic reticulum. Immunocytochemical analysis also showed
      that complex glycans are associated with the peripheral region of PAC vesicles
      but not the electron-dense cores, indicating that Golgi-derived glycoproteins are
      incorporated into the PAC vesicles. These results suggest that the unique PAC
      vesicles might mediate a transport pathway for insoluble aggregates of storage
      proteins directly to protein storage vacuoles.

PMID- 9596641
TI  - 14-3-3 proteins are part of an abscisic acid-VIVIPAROUS1 (VP1) response complex
      in the Em promoter and interact with VP1 and EmBP1.
AB  - Protein-DNA complexes were formed when nuclear extracts from embryogenic rice
      suspension cultures or maize embryos were incubated with an abscisic acid
      VIVIPAROUS1 (VP1) response element (Em1a) from the Em promoter. Monoclonal
      antibodies generated to GF14, a 14-3-3 protein from plants, resulted in gel
      retardation of the Em1a-protein complexes. Antibodies generated to the C and N
      termini of GF14 detected protein isoforms in rice nuclear and cytoplasmic
      extracts, but no differences in distribution of the GF14 isoforms were recognized
      between the nucleus and cytoplasm or when abscisic acid-treated and untreated
      tissues were compared. When recombinant GF14 fusion proteins from rice were added
      to nuclear extracts, novel complexes were formed that required the dimerization
      domain of GF14. Chemical cross-linking showed that GF-14 interacted with the
      basic leucine zipper factor EmBP1, which binds specifically to Em1a, and with
      VP1, which transactivates Em through Em1a. GF14 proteins from rice were shown to
      interact with VP1 in yeast through the dimerization domain of GF14. Our results
      indicated that GF14 interacts with both site-specific DNA binding proteins (i.e.,
      EmBP1) and tissue-specific regulatory factors (i.e., VP1) and may provide a
      structural link between VP1 and the Em1a transcriptional complex.

PMID- 9596643
TI  - Molecular characterization of the PEND protein, a novel bZIP protein present in
      the envelope membrane that is the site of nucleoid replication in developing
      plastids.
AB  - Plastid nucleoids are known to bind to the envelope membrane in developing
      chloroplasts. Here, plastid DNA is extensively replicated. We previously detected
      a DNA binding protein in the inner envelope membranes of developing plastids in
      pea and named it PEND (for plastid envelope DNA binding) protein. In this study,
      we report on the structure and molecular characterization of a cDNA for the PEND
      protein. As a result of screening cDNA libraries in lambdagt11 with one of the
      target sequences of the PEND protein as a probe, we obtained a clone (PD2) for a
      novel DNA binding protein consisting of 633 amino acid residues. Analysis of the
      N-terminal sequence of the purified PEND protein indicated that the transit
      peptide is just 16 residues long. The PEND protein was detected specifically in
      the plastid envelope membrane of young unopened leaf buds by immunoblot analysis.
      The PEND protein consists of a basic region plus zipper region, an unprecedented
      sextuple repeat region, and a putative membrane-spanning region. The basic region
      with a zipper region seems to have diverged from that of other plant
      transcription factors. In addition, the PEND protein could be a distant homolog
      of the trans-Golgi network integral membrane proteins. The PEND protein is
      therefore a novel type of DNA binding protein that binds to the membrane as an
      intrinsic membrane protein.

PMID- 9596642
TI  - Molecular characterization of a tyrosine-specific protein phosphatase encoded by
      a stress-responsive gene in Arabidopsis.
AB  - Protein tyrosine kinases and phosphatases play a vital role in the regulation of
      cell growth and differentiation in animal systems. However, none of these enzymes
      has been characterized from higher plants. In this study, we isolated a cDNA
      encoding a putative protein tyrosine phosphatase (PTPase) from Arabidopsis
      (referred to as AtPTP1). The expression level of AtPTP1 is highly sensitive to
      environmental stresses. High-salt conditions increased AtPTP1 mRNA levels,
      whereas cold treatment rapidly eliminated the AtPTP1 transcript. The recombinant
      AtPTP1 protein specifically hydrolyzed phosphotyrosine, but not
      phosphoserine/threonine, in protein substrates. Site-directed mutagenesis defined
      two highly conserved amino acids, cysteine-265 and aspartate-234, as being
      essential for the phosphatase activity of the AtPTP1 protein, suggesting a common
      catalytic mechanism for PTPases from all eukaryotic systems. In summary, we have
      identified AtPTP1 as a tyrosine-specific protein phosphatase that may function in
      stress responses of higher plants.

PMID- 9596644
TI  - Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic
      leukemia.

PMID- 9596645
TI  - Cloning and characterization of two Toll/Interleukin-1 receptor-like genes TIL3
      and TIL4: evidence for a multi-gene receptor family in humans.
AB  - Remarkable structural and functional similarities exist between the Drosophila
      Toll/Cactus/Dorsal signaling pathway and the mammalian cytokine-mediated
      interleukin-1 receptor (IL-1R)/I-kappaB/NF-kappaB activation cascade. In addition
      to a role regulating dorsal-ventral polarity in the developing Drosophila embryo,
      signaling through Drosophila Toll (dToll) activates the nonclonal, or innate,
      immune response in the adult fly. Recent evidence indicates that a human
      homologue of the dToll protein participates in the regulation of both innate and
      adaptive human immunity through the activation of NF-kappaB and the expression of
      the NF-kappaB-controlled genes IL-1, IL-6, and IL-8, thus affirming the
      evolutionary conservation of this host defense pathway. We report here the
      cloning of two novel human genes, TIL3 and TIL4 (Toll/IL-1R-like-3, -4) that
      exhibit homology to both the leucine-rich repeat extracellular domains and the IL
      1R-like intracellular domains of human and Drosophila Toll. Northern analysis
      showed distinctly different tissue distribution patterns with TIL3 expressed
      predominantly in ovary, peripheral blood leukocytes, and prostate, and TIL4
      expressed primarily in peripheral blood leukocytes and spleen. Chromosomal
      mapping by fluorescence in situ hybridization localized the TIL3 gene to
      chromosome 1q41-42 and TIL4 to chromosome 4q31.3-32. Functional studies showed
      that both TIL3 and TIL4 are able to activate NF-kappaB, though in a cell type
      dependent fashion. Together with human Toll, TIL3 and TIL4 encode a family of
      genes with conserved structural and functional features involved in immune
      modulation.

PMID- 9596646
TI  - The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of
      the MTG8(ETO) family.
AB  - The t(16;21)(q24;q22) translocation is a rare but recurrent chromosomal
      abnormality associated with therapy-related myeloid malignancies and a variant of
      the t(8;21) translocation in which the AML1 gene on chromosome 21 is rearranged.
      Here we report the molecular definition of this chromosomal aberration in four
      patients. We cloned cDNAs from the leukemic cells of a patient carrying t(16;21)
      by the reverse transcription polymerase chain reaction using an AML1-specific
      primer. The structural analysis of the cDNAs showed that AML1 was fused to a
      novel gene named MTG16 (Myeloid Translocation Gene on chromosome 16) which shows
      high homology to MTG8 (ETO/CDR) and MTGR1. Northern blot analysis using MTG16
      probes mainly detected 4.5 kb and 4.2 kb RNAs, along with several other minor
      RNAs in various human tissues. As in t(8;21), the t(16;21) breakpoints occurred
      between the exons 5 and 6 of AML1, and between the exons 1 and 2 or the exons 3
      and 4 of MTG16. The two genes are fused in-frame, resulting in the characteristic
      chimeric transcripts of this translocation. Although the reciprocal chimeric
      product, MTG16-AML1, was also detected in one of the t(16;21) patients, its
      protein product was predicted to be truncated. Thus, the AML1-MTG16 gene fusion
      in t(16;21) leukemia results in the production of a protein that is very similar
      to the AML1-MTG8 chimeric protein.

PMID- 9596647
TI  - Prevention of marrow graft rejection without induction of graft-versus-host
      disease by a cytotoxic T-cell clone that recognizes recipient alloantigens.
AB  - In allogeneic marrow transplantation, donor T cells that recognize recipient
      alloantigens prevent rejection but also cause graft-versus-host disease (GVHD).
      To evaluate whether the ability to prevent marrow graft rejection could be
      dissociated from the ability to cause GVHD, we generated a panel of four
      different CD8 cytotoxic T-lymphocyte clones specific for H2(d) alloantigens.
      Three of the clones caused no overt toxicity when as many as 20 x 10(6) cells
      were infused intravenously into irradiated H2(d)-positive recipients, and one
      clone caused acute lethal toxicity within 1 to 3 days after transferring 10 x
      10(6) cells into H2(d)-positive recipients. One clone that did not cause toxicity
      was able to prevent rejection of (C57BL/6J x C3H/HeJ)F1 marrow in 800 cGy
      irradiated (BALB/cJ x C57BL/6J)F1 recipients without causing GVHD. Large numbers
      of cells and exogenously administered interleukin-2 were required to prevent
      rejection. These results with different CD8 clones suggest that GVHD and
      prevention of rejection could be separable effects mediated by distinct
      populations of donor T cells that recognize recipient alloantigens.

PMID- 9596648
TI  - Non-host-reactive donor CD8+ T cells of Tc2 phenotype potently inhibit marrow
      graft rejection.
AB  - Donor CD8+ T cells capable of host reactivity inhibit marrow graft rejection, but
      also generate graft-versus-host disease (GVHD). To evaluate whether the Tc1- and
      Tc2-type subsets of CD8 cells might inhibit rejection without host reactivity, we
      established an F1 into-parent murine bone marrow transplant model. Donor Tc1 and
      Tc2 cells were generated that preferentially secreted type I or type II
      cytokines; both subsets possessed potent cytolytic function, and clonally deleted
      host-type allospecific precursor CTL in vitro. B6 hosts receiving 950 cGy
      irradiation did not reject the donor marrow (F1 chimerism of 78.6%; n = 10),
      whereas hosts receiving 650 cGy rejected the donor marrow (3.8% chimerism; n =
      8). At 650 cGy irradiation, the addition of Tc2 cells to the F1 marrow resulted
      in extensive F1 chimerism (70.8%) in 8 of 8 recipients; in contrast,
      alloengraftment was not consistently observed in mice receiving Tc1 cells or
      unmanipulated CD8 cells. Furthermore, when the preparative regimen was further
      reduced to 600 cGy, only hosts receiving the Tc2-type cells did not reject the F1
      marrow. We conclude that Tc2 cells potently inhibit marrow graft rejection
      without inducing an alloaggressive response and that non-host-reactive Tc2 cells
      therefore facilitate engraftment across genetic barriers with reduced GVHD.

PMID- 9596649
TI  - Differential effects of anti-Fas ligand and anti-tumor necrosis factor alpha
      antibodies on acute graft-versus-host disease pathologies.
AB  - Both tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) have been
      implicated in the pathogenesis of graft-versus-host disease (GVHD). In this
      study, we examined the ameliorating effects of neutralizing anti-FasL and/or anti
      TNFalpha monoclonal antibody (MoAb) in a lethal acute GVHD model in mice. Whereas
      the treatment with either anti-FasL or anti-TNFalpha MoAb alone significantly
      delayed the mortality and improved the body weight, a complete protection was
      achieved by the administration of both MoAbs. Pathological examination indicated
      differential effects of anti-FasL or anti-TNFalpha MoAb on GVHD-associated
      pathologies. Hepatic lesion was improved by anti-FasL but not anti-TNFalpha MoAb.
      In contrast, intestinal lesion was improved by anti-TNFalpha but not anti-FasL
      MoAb. Cutaneous and splenic lesions were improved by either MoAb. The combination
      of both MoAbs improved all these lesions. These results indicate that FasL and
      TNFalpha differentially contribute to the GVHD pathologies and a complete
      protection from mortality can be achieved by neutralization of both FasL and
      TNFalpha.

PMID- 9596650
TI  - Quantitative long-term culture-initiating cell assays require accessory cell
      depletion that can be achieved by CD34-enrichment or 5-fluorouracil exposure.
AB  - Characterization of hematopoietic cells and measurement of their proliferative
      potential is critical in many research and clinical applications. Because in vivo
      assay of human cells is not possible and xenogeneic assays are not yet routine,
      in vitro assays such as the long-term culture-initiating cell (LTC-IC) assay have
      been widely adopted. This study investigated LTC-IC assay linearity and
      reproducibility and resulting implications with respect to quantitation of
      primitive cell expansion. Measurement of secondary colony-forming cells (2
      degrees CFCs) from 5-week cultures of bone marrow (BM) mononuclear cells (MNCs)
      showed that 2 degrees CFC frequency varied with assay plating density in a
      nonlinear fashion. The measured 2 degrees CFC frequency increased from 4.6 to
      63.8 (per 10(5) MNCs) as assay plating density was decreased from 5 x 10(5) to 2
      x 10(4) MNCs per well (P < 10(-6), n = 37). In contrast, assay of CD34-enriched
      cells was linear within the range studied. Assays of cells obtained from
      expansion cultures initiated with either MNCs or CD34-enriched cells were also
      nonlinear. Consequently, calculated 2 degrees CFC expansion ratios were ambiguous
      and dependent on the assay plating densities used. Limiting dilution analysis
      (LDA) results were also nonlinear, with LTC-IC frequency increasing from 8. 2 to
      22.4 per 10(5) MNCs (P < 10(-4), n = 100) as assay plating densities were
      decreased. Despite the nonlinearity, 2 degrees CFC and LTC-IC assay results were
      consistent and reproducible over time with different samples and techniques and
      gave a semiquantitative indication of relative primitive cell frequency. Although
      CD34-enriched cells gave linear assay output, purification of cells for every
      assay is impractical. Therefore, exposure of cells to 5-fluorouracil (5-FU) was
      explored for improving assay linearity. Incubation of MNCs in 250 microg/mL 5-FU
      for 1 to 2 hours depleted accessory cells and resulted in a cell population that
      gave linear 2 degrees CFC readout. The 5-FU-resistant LTC-ICs accounted for 49%
      of the total LTC-IC population, adding the potential benefit of restricting assay
      measurement to more primitive noncycling LTC-ICs. Consequently, similar linear
      assay results can be obtained with either the bulk 2 degrees CFC or LDA LTC-IC
      methods after 5-FU, but multiple plating densities are nevertheless still
      required in both methods due to the greater than 100-fold range in primitive cell
      frequency present in normal human donor BM.

PMID- 9596651
TI  - Thrombopoietin enhances the production of myeloid cells, but not megakaryocytes,
      in juvenile chronic myelogenous leukemia.
AB  - We previously reported the aberrant growth of granulocyte-macrophage (GM)
      progenitors induced by a combination of stem cell factor (SCF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) in juvenile chronic myelogenous
      leukemia (JCML). We examined here the effects of thrombopoietin (TPO) on the
      proliferation and differentiation of hematopoietic progenitors in JCML. In serum
      deprived single-cell cultures of normal bone marrow (BM) CD34+CD38high cells, the
      addition of TPO to the culture containing SCF + GM-CSF resulted in an increase in
      the number and size of GM colonies. In the JCML cultures, in contrast, the number
      of SCF + GM-CSF-dependent GM colonies was not increased by the addition of TPO.
      However, the TPO addition caused an enlargement of GM colonies in cultures from
      the JCML patients to a significantly greater extent compared with the normal
      controls. There was no difference in the type of the constituent cells of GM
      colonies with or without TPO grown by JCML BM cells. A flow cytometric analysis
      showed that the c-Mpl expression was found on CD13+ myeloid cells generated by
      CD34+CD38high BM cells from JCML patients, but was at an undetectable level in
      normal controls. The addition of TPO to the culture containing SCF or SCF + GM
      CSF caused a significant increase in the production of GM colony-forming cells by
      JCML CD34+CD38neg/low population, indicating the stimulatory effects of TPO on
      JCML primitive hematopoietic progenitors. Normal BM cells yielded a significant
      number of megakaryocytes as well as myeloid cells in response to a combination of
      SCF, GM-CSF, and/or TPO. In contrast, megakaryocytic cells were barely produced
      by the JCML progenitors. Our results may provide a fundamental insight that the
      administration of TPO enhances the aberrant growth of GM progenitors rather than
      the recovery of megakaryocytopoiesis.

PMID- 9596652
TI  - Suppression of hematopoietic activity in tenascin-C-deficient mice.
AB  - Tenascin-C (TN-C), a member of the extracellular matrix (ECM) glycoprotein
      family, is expressed on the surface of stromal cells in the hematopoietic system
      or lymphoid organs. Recently, TN-C-deficient mutant mice produced by TN-C gene
      targeting through homologous recombination were shown to develop normally,
      although TNs have been reported to play important roles in organogenesis and
      carcinogenesis. In the present study, we found that colony-forming capacity of
      bone marrow (BM) cells was considerably lower in TN-C-deficient mice (a decrease
      of approximately 35% from control), although their mononuclear cell count and BM
      architecture showed no significant difference from those of normal mice.
      Furthermore, in long-term BM culture in vitro, hematopoietic cell production (a
      decrease of approximately 40% in Dexter's condition and of approximately 65% in
      Whitlock-Witte's condition from control), colony-forming capacity of the produced
      cells (a decrease of approximately 60% from control), and longevity of the
      cultures were markedly lower in the TN-C-deficient mice than in control mice,
      whereas hematopoiesis in the TN-C-deficient mutant mice was sustained. The
      addition of TN-C glycoprotein to long-term BM cultures of TN-C-deficient mice
      clearly induced the recovery of hematopoietic cell production and colony-forming
      capacity of hematopoietic progenitor cells. Thus, these results provide direct
      evidence that an ECM glycoprotein component, TN-C, plays a relevant role in
      hematopoiesis through interactions between stromal cells and hematopoietic
      progenitor cells.

PMID- 9596653
TI  - The Notch ligand, Jagged-1, influences the development of primitive hematopoietic
      precursor cells.
AB  - We examined the expression of two members of the Notch family, Notch-1 and Notch
      2, and one Notch ligand, Jagged-1, in hematopoietic cells. Both Notch-1 and Notch
      2 were detected in murine marrow precursors (Lin-Sca-1+c-kit+). The Notch ligand,
      Jagged-1, was not detected in whole marrow or in precursors. However, Jagged-1
      was seen in cultured primary murine fetal liver stroma, cultured primary murine
      bone marrow stroma, and in stromal cell lines. These results indicate a potential
      role for Notch-Notch ligand interactions in hematopoiesis. To further test this
      possibility, the effect of Jagged-1 on murine marrow precursor cells was assessed
      by coculturing sorted precursor cells (Lin-Sca-1+c-kit+) with a 3T3 cell layer
      that expressed human Jagged-1 or by incubating sorted precursors with beads
      coated with the purified extracellular domain of human Jagged-1 (Jagged-1(ext)).
      We found that Jagged-1, presented both on the cell surface and on beads, promoted
      a twofold to threefold increase in the formation of primitive precursor cell
      populations. These results suggest a potential use for Notch ligands in expanding
      precursor cell populations in vitro.

PMID- 9596655
TI  - Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor
      cells induced by interleukin-8.
AB  - Previously, we have shown that interleukin (IL)-8 induces the rapid (15 to 30
      minutes) mobilization of hematopoietic progenitor cells (HPC) in mice. Because
      integrins are essential for adhesion and transendothelial migration of HPC, we
      studied the involvement of the beta2-integrin leukocyte function-associated
      antigen-1 (LFA-1) in IL-8-induced mobilization. After a single injection of
      blocking anti-LFA-1 antibodies, no mobilization of colony-forming cells was
      observed. In addition, when mice were pretreated with anti-LFA-1 or saline and
      subsequently injected with 30 microg of IL-8, mobilization of HPC was completely
      blocked. We showed that this was not due to anti-LFA-1 antibodies affecting
      colony formation, as addition of anti-LFA-1 antibodies to colony cultures in
      semisolid medium had no inhibitory activity. Also, anti-intercellular adhesion
      molecule (ICAM)-1 antibodies, directed to the main ligand of LFA-1 significantly
      inhibited the IL-8-induced mobilization. Furthermore, IL-1-induced mobilization
      was significantly inhibited by anti-LFA-1 antibodies. Because LFA-1 is reported
      to be expressed on more differentiated HPC, it was considered that the IL-8
      induced mobilization of more primitive HPC would not be blocked by anti-LFA-1
      antibodies. Transplantation of blood-derived mononuclear cells (MNC) from IL-8
      mobilized animals pretreated with anti-LFA-1 antibodies protected only 25% of
      lethally irradiated recipient mice, whereas the radioprotection rate of control
      mice transplanted with MNC derived from IL-8-mobilized animals was 86% (P < .01).
      Anti-LFA-1 antibodies did not interfere with stem cell homing, as transplantation
      of IL-8-mobilized blood MNC, incubated in vitro with these antibodies resulted in
      100% radioprotection. We conclude that anti-LFA-1 antibodies completely prevent
      the rapid mobilization of colony-forming cells and of cells with radioprotective
      capacity induced by IL-8. These results indicate a major role for the beta2
      integrin LFA-1 in the IL-8-induced mobilization of hematopoietic stem cells.

PMID- 9596654
TI  - Multiple inhibitory cytokines induce deregulated progenitor growth and apoptosis
      in hematopoietic cells from Fac-/- mice.
AB  - We used a murine model containing a disruption of the murine homologue (Fac) of
      Fanconi Anemia group C (FAC) to evaluate the role of Fac in the pathogenesis of
      bone marrow (BM) failure. Methylcellulose cultures of BM cells from Fac-/- and
      Fac+/+ mice were established to examine the growth of multipotent and lineage
      restricted progenitors containing inhibitory cytokines, including interferon
      gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and macrophage
      inflammatory protein-1alpha (MIP-1alpha). Clonogenic growth of Fac-/- progenitors
      was reduced by 50% at 50- to 100-fold lower concentrations of all inhibitory
      cytokines evaluated. We hypothesized that the aberrant responsiveness to
      inhibitory cytokines in clonogenic cells may be a result of deregulated
      apoptosis. To test this hypothesis, we performed the TUNEL assay on purified
      populations of primary BM cells enriched for hematopoietic progenitors or
      differentiated myeloid cells. After stimulation with TNF-alpha, accentuated
      apoptosis was observed in both populations of Fac-/- cells. In addition,
      deregulated apoptosis was also noted in the most immature phenotypic population
      of hematopoietic cells after stimulation with MIP-1alpha. Together these data
      suggest a role of Fac in affecting the signaling of multiple cytokine pathways
      and support cytokine-mediated apoptosis as a major mechanism responsible for BM
      failure observed in FA patients.

PMID- 9596656
TI  - Rhodamine-123 staining in hematopoietic stem cells of young mice indicates
      mitochondrial activation rather than dye efflux.
AB  - Low-intensity fluorescence of rhodamine-123 (Rh-123) discriminates a quiescent
      hematopoietic stem cell (HSC) population in mouse bone marrow, which provides
      stable, long-term hematopoiesis after transplantation. Rh-123 labels mitochondria
      with increasing intensity proportional to cellular activation, however the
      intensity of staining also correlates with the multidrug resistance (MDR)
      phenotype, as Rh-123 is a substrate for P-glycoprotein (P-gp). To address the
      mechanisms of long-term repopulating HSC discrimination by Rh-123, mouse bone
      marrow stem and progenitor cells were isolated based on surface antigen
      expression and subsequently separated into subsets using various fluorescent
      probes sensitive to mitochondrial characteristics and/or MDR function. We
      determined the cell cycle status of the separated populations and tested for HSC
      function using transplantation assays. Based on blocking studies using MDR
      modulators, we observed little efflux of Rh-123 from HSC obtained from young (3-
      to 4-week-old) mice, but significant efflux from HSC derived from older animals.
      A fluorescent MDR substrate (Bodipy-verapamil, BodVer) and Rh-123 both segregated
      quiescent cells into a dim-staining population, however Rh-123-based separations
      resulted in better enrichment of HSC function. Similar experiments using two
      other fluorescent probes with specificity for either mitochondrial mass or
      membrane potential indicated that mitochondrial activation is more important than
      either mitochondrial mass or MDR function in defining HSC in young mice. This
      conclusion was supported by morphologic studies of cell subsets separated by Rh
      123 staining.

PMID- 9596657
TI  - Thrombopoietin requires additional megakaryocyte-active cytokines for optimal ex
      vivo expansion of megakaryocyte precursor cells.
AB  - Little is known concerning the interaction of thrombopoietin (TPO) with other
      megakaryocyte-active cytokines in directing the early events of megakaryocyte
      development. Culture of CD34(+) cells in interleukins (IL) -1, -6, -11, plus stem
      cell factor (SCF; S) results in a 10- to 12-fold expansion in total cell numbers,
      whereas total CD41(+) megakaryocytes are expanded approximately 120-fold over
      input levels. Addition of TPO to IL-1, -6, -11, S generates a biphasic
      proliferation of CD41(+) cells, accelerates their rate of production, and results
      in an ex vivo expansion of more than 200-fold. The addition of Flt-3 ligand (FL)
      increases CD41+ cell expansion to approximately 380-fold over input levels. In
      the absence of TPO, approximately 95% of the expanded cells show the phenotype of
      promegakaryoblasts; TPO and/or FL addition increases CD41 antigen density and
      ploidy in a subpopulation of promegakaryoblasts. A moderate (approximately
      sevenfold) expansion of megakaryocyte progenitor cells (colony-forming unit
      megakaryocyte) occurs in the presence of IL-1, -6, -11, S, and the addition of
      TPO to this cocktail yields an approximately 17-fold expansion. We conclude that
      early proliferative events in megakaryocyte development in vitro are regulated by
      multiple cytokines, and that TPO markedly affects these early developmental
      steps. However, by itself, TPO is neither necessary nor sufficient to generate a
      full proliferative/maturational in vitro response within the megakaryocyte
      compartment. TPO clearly affects terminal differentiation and the development of
      (some) high-ploidy human megakaryocytes. However, its limited in vitro actions on
      human cell polyploidization suggest that additional megakaryocyte-active
      cytokines or other signals are essential for the maximal development of human
      megakaryocytes.

PMID- 9596658
TI  - Growth inhibition of granulocyte-macrophage colony-forming cells by human
      cytidine deaminase requires the catalytic function of the protein.
AB  - Previous studies have indicated that cytidine deaminase (CDD) is a potent growth
      inhibitor of granulocyte-macrophage colony-forming cells (GM-CFC). In this study,
      we have undertaken molecular cloning and purification of recombinant human CDD to
      elucidate the growth regulatory potential and mechanism behind the growth
      suppressive effect. The purified protein had a specific activity of 1.35 x 10(5)
      U/mg and a Km value of 30 micromol/L. In the GM-CFC assay, the recombinant
      protein was shown to reduce colony formation to 50% at 16 pmol/L concentration.
      Similarly, as was observed with CDD derived from granulocyte extract, the effect
      depended on the presence of thymidine (>/= 4 x 10(-5) mol/L). These results imply
      that CDD is an extremely potent inhibitor of GM-CFC and that no additional factor
      from the granulocyte extract is required for the growth inhibitory effect.
      Modification of CDD by truncation from the C-terminal end, or by amino acid
      substitution of an active site glutamate residue, eliminated both the enzyme
      activity and the growth regulatory potential of CDD. Furthermore, CDD from
      Escherichia coli was found to be even more effective than human CDD in growth
      suppression of GM-CFC, with 10-fold higher inhibitory activity corresponding to a
      10-fold higher enzymatic activity. Taken together, these results show that the
      catalytic nucleoside deaminating function of the protein is essential for the
      growth suppressive effect of CDD. Most probably, CDD exerts growth inhibition by
      depleting the cytidine and deoxycytidine pool required for DNA synthesis, as
      addition of deoxycytidine monophosphate, which is not a substrate for CDD,
      neutralizes the inhibiting effect.

PMID- 9596659
TI  - NF-kappaB transcription factors are involved in normal erythropoiesis.
AB  - NF-kappaB/Rel designates a widely distributed family of transcription factors
      involved in immune and acute phase responses. Here, the expression and function
      of NF-kappaB factors in erythroid proliferation and differentiation were
      explored. In an erythroleukemia cell line, TF-1, high levels of p105/p50,
      p100/p52, p65, and IkappaBalpha were detected 24 hours after growth factor
      deprivation. In response to granulocyte-macrophage colony-stimulating factor (GM
      CSF) stimulation, significant induction of p52 expression was observed. GM-CSF
      also induced nuclear translocation of both p52 and p65. No induction of NF-kappaB
      factors was observed with erythropoietin stimulation of TF-1 cells.
      Overexpression of p52 and p65 in TF-1 cells by transient transfection resulted in
      significant induction of a kappaB-TATA-luciferase reporter plasmid, showing that
      these factors are functional in vivo in erythroid cells. To determine whether NF
      kappaB factors may play a role in normal erythropoiesis, levels of these factors
      were determined in burst-forming unit-erythroid (BFU-E)-derived cells at
      different stages of differentiation. The NF-kappaB factors p105/p50, p100/p52,
      and p65 were highly expressed in early BFU-E-derived precursors, which are
      rapidly proliferating, and declined during maturation. Furthermore, nuclear
      levels of NF-kappaB factors p50, p52, and p65 were higher in less mature
      precursors (day 10 BFU-E-derived cells) compared with more differentiated (day
      14) erythroblasts. In nuclear extracts from day 10 BFU-E-derived cells, p50, p52,
      and p65 were able to form complexes, which bound to kappaB sites in the promoters
      of both the c-myb and c-myc genes, suggesting that c-myb and c-myc may be among
      the kappaB-containing genes regulated by NF-kappaB factors in normal erythroid
      cells. Taken together, these data show that NF-kappaB factors are modulated by GM
      CSF and suggest they function to regulate specific kappaB containing genes
      involved in erythropoiesis.

PMID- 9596660
TI  - In vitro identification of single CD34+CD38- cells with both lymphoid and myeloid
      potential.
AB  - Human hematopoietic stem cells are pluripotent, ie, capable of producing both
      lymphoid and myeloid progeny, and are therefore used for transplantation and gene
      therapy. An in vitro culture system was developed to study the multi-lineage
      developmental potential of a candidate human hematopoietic stem cell population,
      CD34+CD38- cells. CD34+CD38- cells cocultivated on the murine stromal line S17
      generated predominantly CD19(+) B-cell progenitors. Transfer of cells from S17
      stroma to myeloid-specific conditions ("switch culture") showed that a fraction
      of the immunophenotypically uncommitted CD19- cells generated on S17 stroma had
      myeloid potential (defined by expression of CD33 and generation of colony-forming
      unit-cells). Using the switch culture system, single CD34+CD38- cells were
      assessed for their lymphoid and myeloid potential. Nineteen of 50 (38%) clones
      generated from single CD34+CD38- cells possessed both B-lymphoid and myeloid
      potential. 94.7% of the CD34+CD38- cells with lympho-myeloid potential were late
      proliferating (clonal appearance after 30 days), demonstrating that
      pluripotentiality is detected significantly more often in quiescent progenitors
      than in cytokine-responsive cells (P = .00002). The S17/switch culture system
      permits the in vitro assessment of the pluripotentiality of single human
      hematopoietic cells.

PMID- 9596661
TI  - Antibodies to protease-activated receptor 3 inhibit activation of mouse platelets
      by thrombin.
AB  - Recent studies of mice deficient in the thrombin receptor, protease-activated
      receptor 1 (PAR1), provided definitive evidence for the existence of a second
      thrombin receptor in mouse platelets. We recently identified a new thrombin
      receptor designated protease-activated receptor 3 (PAR3). The mRNA encoding a
      mouse homologue of PAR3 was highly expressed in mouse splenic megakaryocytes,
      making it a good candidate for the missing mouse platelet thrombin receptor. We
      now report that PAR3 protein is expressed on the surface of mouse platelets and
      that PAR3 antibodies partially inhibit activation of mouse platelets by thrombin
      but not U46619, a thromboxane receptor agonist. These observations suggest that
      PAR3 contributes to mouse platelet activation by thrombin.

PMID- 9596662
TI  - Methylenetetrahydrofolate reductase C677T mutation, plasma homocysteine, and
      folate in subjects from northern Italy with or without angiographically
      documented severe coronary atherosclerotic disease: evidence for an important
      genetic-environmental interaction.
AB  - Moderate elevation of plasma total homocysteine (tHcy) is a strong and
      independent risk factor for coronary artery disease (CAD). It can result from
      genetic or nutrient-related disturbances in the transsulfuration or remethylation
      pathways for Hcy metabolism. A point mutation (C677T; Ala-to-Val) in the gene
      encoding the 5, 10-methylenetetrahydrofolate reductase (MTHFR) has been recently
      reported to render the enzyme thermolabile and less active. Studies on the role
      of this mutation as a risk factor for CAD have given conflicting results. We
      studied a total of 415 subjects, 278 with angiographically documented multivessel
      CAD and 137 with angiographically documented normal coronary arteries. The
      overall frequency of the MTHFR V/V homozygous genotype was 15.7% (with 52.5%
      heterozygous and 31.8% normal). Subgroup analysis showed no significant
      differences between CAD and CAD-free subjects. A genotype/phenotype correlation
      study showed a marked effect of folate on the association between MTHFR genotypes
      and tHcy. Among individuals with folate levels below the median (11.5 nmol/L),
      fasting tHcy was significantly increased not only in V/V homozygotes (by 59%) but
      also, at intermediate values, in A/V heterozygotes (by 21% on average).
      Conversely, the mutation resulted neutral with respect to tHcy levels in subjects
      with adequate folate levels. We conclude that, in our population, the MTHFR C677T
      mutation is rather common, but it does not appear to be associated per se to CAD.
      A genetic-environmental interaction may contribute to the vascular risk by
      elevating tHcy when folate status is low.

PMID- 9596663
TI  - Fluid shear stress attenuates tumor necrosis factor-alpha-induced tissue factor
      expression in cultured human endothelial cells.
AB  - Hemodynamic forces modulate various endothelial cell functions under gene
      regulation. Previously, we have shown that fibrinolytic activity of endothelial
      cells is enhanced by the synergistic effects of shear stress and cytokines. In
      this study, we investigated the effect of shear stress on tumor necrosis factor
      (TNF)-alpha-induced tissue factor (TF) expression in cultured human umbilical
      vein endothelial cells (HUVECs), using a modified cone-plate viscometer. Shear
      stresses at physiological levels reduced TNF-alpha (100 U/mL)-induced TF
      expression at both mRNA and antigen levels, in a shear-intensity and exposure
      time dependent manner, whereas shear stress itself did not induce TF expression
      in HUVECs. TF expressed on the cell surfaces measured by flow cytometry using an
      anti-TF monoclonal antibody (HTF-K180) was also decreased to one third by shear
      force applied at 18 dynes/cm2 for 15 hours before and 6 hours after TNF-alpha
      stimulation. Furthermore, functional activity of TF, as assessed by the
      activation of factor X in the presence of FVIIa and Ca2+, was also decreased by
      shear application. However, the stability of TF mRNA was not decreased in the
      presence of shear stress. These results suggest that shear force acts as an
      important regulator of TF expression in endothelium at the transcriptional level.

PMID- 9596664
TI  - Plasmin can reduce the function of human beta2 glycoprotein I by cleaving domain
      V into a nicked form.
AB  - beta2-Glycoprotein I (beta2GPI) is a highly glycosylated plasma protein with the
      ability to bind negatively charged substances such as DNA, heparin, dextran
      sulfate, and negatively charged phospholipids. The most relevant physiological
      role of beta2GPI is supposed to be the regulation of the function of anionic
      phospholipids like cardiolipin (CL). beta2GPI consists of a single polypeptide
      chain (326 amino acid residues) with a molecular mass of about 50 kD and with
      five tandem repeated domains (I, II, III, IV, and V). In the previous study, we
      found that factor Xa can produce the nicked form by cleaving Lys 317-Thr 318,
      using recombinant human domain V (r-Domain V). However, the reaction was
      extremely slow. In the present paper, we found that plasmin can produce the
      nicked form of domain V, using recombinant domain V (r-Domain V) and beta2GPI
      from human plasma. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      r-Domain V was rapidly cleaved into a nicked form by plasmin, very slowly by
      factor Xa, but not by thrombin, tissue-type plasminogen activator, urokinase, and
      tissue factor/factor VIIa. The cleavage site of r-Domain V and beta2GPI by
      plasmin was proved to be Lys 317-Thr 318 by amino acid sequence analysis of the
      digest and of the C-terminal peptide isolated by high-performance liquid
      chromatography. The cleavage was completely inhibited by plasmin inhibitor
      (alpha2PI). The nicked form was demonstrated to show reduced affinity for CL with
      a dissociation constant of one order of magnitude larger than that of the intact
      beta2GPI. To determine whether the specific cleavage of beta2GPI by plasmin can
      occur also in plasma, human plasma was first acid-treated to inactivate alpha2PI
      and then incubated with urokinase. About 12% of beta2GPI in plasma was nicked
      when alpha2PI activity decreased to 80%. The nicked form was not generated in
      plasminogen-depleted plasma. These results suggest that plasmin can produce the
      nicked form of beta2GPI with the reduced ability to bind phospholipids in vivo.

PMID- 9596665
TI  - Analysis of ferritins in lymphoblastoid cell lines and in the lens of subjects
      with hereditary hyperferritinemia-cataract syndrome.
AB  - Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal and
      dominant disease caused by heterogeneous mutations in the iron responsive element
      (IRE) of the 5' untranslated flanking region of ferritin L-chain mRNA, which
      reduce the binding to the trans iron regulatory proteins and make L-chain
      synthesis constitutively upregulated. In the several families identified so far,
      the serum and tissue L-ferritin levels are fivefold to 20-fold higher than in
      nonaffected control subjects, iron metabolism is apparently normal, and the only
      relevant clinical symptom is early onset, bilateral cataract. Some pathogenetic
      aspects of HHCS remain obscure, with particular reference to the isoferritins
      produced by HHCS cells, as well as the mechanism of cataract formation. We
      analyzed lymphoblastoid cell lines obtained from two nonaffected control subjects
      and from HHCS patients carrying the substitution A40G (Paris-1), G41C (Verona-1),
      and the deletion of the residues 10-38 (Verona-2) in the IRE structure. Enzyme
      linked immunosorbent assays specific for the H- and L-type ferritins showed that
      L-ferritin levels were up to 20-fold higher in HHCS than in control cells and
      were not affected by iron supplementation or chelation. Sequential
      immunoprecipitation experiments of metabolically-labeled cells with specific
      antibodies indicated that in HHCS cells about half of the L-chain was assembled
      in L-chain homopolymers, which did not incorporate iron, and the other half was
      assembled in isoferritins with a high proportion of L-chain. In control cells,
      all ferritin was assembled in functional heteropolymers with equivalent
      proportion of H- and L-chains. Cellular and ferritin iron uptake was slightly
      higher in HHCS than control cells. In addition, we analyzed the lens recovered
      from cataract surgery of a HHCS patient. We found it to contain about 10-fold
      more L-ferritin than control lens. The ferritin was fully soluble with a low iron
      content. It was purified and partially characterized. Our data indicate that: (1)
      in HHCS cells a large proportion of L-ferritin accumulates as nonfunctional L
      chain 24 homopolymers; (2) the concomitant fivefold to 10-fold expansion of
      ferritin heteropolymers, with a shift to L-chain-rich isoferritins, does not have
      major effects on cellular iron metabolism; (3) L-chain accumulation occurs also
      in the lens, where it may induce cataract formation by altering the delicate
      equilibrium between other water-soluble proteins (ie, crystallins) and/or the
      antioxidant properties.

PMID- 9596666
TI  - Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are
      associated with hemorrhagic manifestations.
AB  - Factor V inhibitors may develop as spontaneous autoantibodies, as alloantibodies
      after exposure to bovine thrombin preparations, or in factor V-deficient patients
      after plasma therapy. Clinical manifestations range from asymptomatic laboratory
      abnormalities to life-threatening hemorrhage. We have characterized the anti
      factor V antibodies from 12 patients diagnosed with factor V inhibitors. In 8
      patients, hemorrhagic complications (5 autoantibodies and 3 bovine thrombin
      induced alloantibodies) developed, and 4 were asymptomatic (2 autoantibodies and
      2 alloantibodies). The IgG fractions from all 12 patients immunoprecipitated the
      factor Va light chain, but only the 8 IgG fractions associated with hemorrhage
      inhibited factor V activity in a prothrombinase assay. Nine IgG fractions,
      including the 8 patients with hemorrhage, immunoprecipitated the isolated second
      C-type domain (C2). The 8 IgG fractions from the symptomatic patients also
      immunoprecipitated recombinant chimeras containing only the N-terminal third of
      the factor V C2 domain, and isolated recombinant C2 domain abrogated the
      inhibitory effect of the antibodies. Five of the inhibitory IgG fractions blocked
      binding of factor V to phosphatidylserine. These results suggest that inhibitory
      anti-factor V antibodies are associated with hemorrhagic manifestations and
      frequently bind to a common region within the C2 domain, whether originating
      spontaneously or after exposure to bovine thrombin.

PMID- 9596667
TI  - Biochemical and pharmacological properties of SANORG 34006, a potent and long
      acting synthetic pentasaccharide.
AB  - SANORG 34006 is a new sulfated pentasaccharide obtained by chemical synthesis. It
      is an analog of the "synthetic pentasaccharide" (SR 90107/ ORG 31540) which
      represents the antithrombin (AT) binding site of heparin. SANORG 34006 showed a
      higher affinity to human AT than SR 90107/ORG 31540 (kd = 1.4 +/- 0.3 v 48 +/- 11
      nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT
      on factor Xa (1,240 +/- 15 anti-factor Xa U/mg v 850 +/- 27 anti-factor Xa U/mg
      for SR 90107/ORG 31540). In vitro, SANORG 34006 inhibited thrombin generation
      occurring via both the extrinsic and intrinsic pathway. After intravenous (IV) or
      subcutaneous (SC) administration to rabbits, SANORG 34006 displayed a long
      lasting anti-factor Xa activity and inhibition of thrombin generation (TG) ex
      vivo. SANORG 34006 was slowly eliminated after IV or SC administration to rats,
      rabbits, and baboons, showed exceptionally long half-lives (between 9.2 hours in
      rats and 61.9 hours in baboons), and revealed an SC bioavailability near 100%.
      SANORG 34006 displayed antithrombotic activity by virtue of its potentiation of
      the anti-factor Xa activity of AT. It strongly inhibited thrombus formation in
      experimental models of thromboplastin/stasis-induced venous thrombosis in rats
      (IV) and rabbits (SC) (ED50 values = 40.0 +/- 3.4 and 105.0 +/- 9.4 nmol/kg,
      respectively). The duration of its antithrombotic effects closely paralleled the
      ex vivo anti-factor Xa activity. SANORG 34006 enhanced rt-PA-induced thrombolysis
      and inhibited accretion of 125I-fibrinogen onto a preformed thrombus in the
      rabbit jugular vein suggesting that concomitant use of SANORG 34006 during rt-PA
      therapy might be helpful in facilitating thrombolysis and preventing fibrin
      accretion onto the thrombus under lysis. Contrary to standard heparin, SANORG
      34006 did not enhance bleeding in a rabbit ear incision model at a dose that
      equals 10 times the antithrombotic ED50 in this species and, therefore, exhibited
      a favorable therapeutic index. We suggest that SANORG 34006 is a promising
      compound in the treatment and prevention of various thrombotic diseases.

PMID- 9596668
TI  - RhoA and the function of platelet integrin alphaIIbbeta3.
AB  - Integrins respond to "inside-out" signals, which enable them to bind adhesive
      ligands, and ligand binding initiates "outside-in" signals that mediate anchorage
      dependent cellular responses. RhoA is a GTPase that regulates certain actin
      rearrangements and transcriptional events. It has also been implicated in
      integrin signaling, but the exact relationship is not understood. To examine this
      further, platelets were incubated with C3 exoenzyme to adenine diphosphate (ADP)
      ribosylate and inactivate RhoA, and the function of integrin alphaIIbbeta3 was
      studied. Despite inactivation of >/= 90% of RhoA, platelets exhibited normal
      inside-out signaling, as monitored by agonist-induced binding of a fibrinogen
      mimetic anti-alphaIIbbeta3 antibody and normal fibrinogen-dependent aggregation.
      On the other hand, RhoA inactivation decreased the adhesion of agonist-stimulated
      platelets to fibrinogen (P < .04) and the formation of vinculin-rich focal
      adhesions in platelets that did adhere (P < .001). These effects were selective
      because fibrin clot retraction, a response also dependent on alphaIIbbeta3 and
      actin contractility, was unaffected by C3, as was the content of F-actin in
      resting or agonist-stimulated platelets. Similar results were obtained in a
      Chinese hamster ovary (CHO) cell model system of alphaIIbbeta3: C3 exoenzyme (or
      overexpression of dominant-negative N19RhoA) failed to influence integrin
      activation state, but it blocked the formation of focal adhesions in cells spread
      on fibrinogen. These studies establish that RhoA plays a highly selective role in
      alphaIIbbeta3 signaling, and they identify a subset of responses to integrin
      ligation that may be uniquely dependent on the actin rearrangements regulated by
      this GTPase.

PMID- 9596669
TI  - Whole blood tissue factor procoagulant activity is elevated in patients with
      sickle cell disease.
AB  - We developed a simple assay for the measurement of tissue factor procoagulant
      activity (TF PCA) in whole blood samples that avoids the need for mononuclear
      cell isolation. This method combines convenience of sample collection and
      processing with a high degree of sensitivity and specificity for TF. Using this
      method, we have determined that TF PCA is detectable in whole blood samples from
      normal individuals, which is itself a novel observation. Essentially all PCA
      could be shown to be localized in the mononuclear cell fraction of blood.
      Compared with controls, whole blood TF levels were significantly (P < .000001)
      elevated in patients with sickle cell disease (SCD), regardless of the subtype of
      hemoglobinopathy (SS or SC disease). No significant difference in TF PCA was
      observed between patients in pain crisis compared with those in steady-state
      disease. Because TF functions as cofactor in the proteolytic conversion of FVII
      to FVIIa in vitro, it was expected that an increase in circulating TF PCA would
      lead to an increased in vivo generation of FVIIa. On the contrary, FVIIa levels
      were actually decreased in the plasma of patients with SCD. Plasma TF pathway
      inhibitor (TFPI) antigen levels were normal in SCD patients, suggesting that
      accelerated clearance of FVIIa by the TFPI pathway was not responsible for the
      reduced FVIIa levels. We propose that elevated levels of circulating TF PCA may
      play an important role in triggering the activation of coagulation known to occur
      in patients with SCD. Because TF is the principal cellular ligand for FVIIa, it
      is possible that increased binding to TF accounts for the diminished plasma FVIIa
      levels.

PMID- 9596670
TI  - Correction of abnormal T-cell receptor repertoire during interferon-alpha therapy
      in patients with hairy cell leukemia.
AB  - Patients with the B-cell malignancy hairy cell leukemia (HCL) exhibit a skewed T
      cell repertoire with oligoclonal expression or absence of many members of the T
      cell receptor (TCR) BV gene families. To evaluate whether interferon-alpha (IFN
      alpha) therapy would not only restore normal hematopoiesis, but also the abnormal
      T-cell repertoire, we studied T lymphocytes from a cohort of HCL patients treated
      by IFN-alpha in the past, at initiation, and at several intervals up to 6 years
      of IFN-alpha treatment. The junctional regions from 22 TCRBV gene families were
      analyzed after polymerase chain reaction amplification of cDNA (RT-PCR) using
      family specific primers. In all seven patients improvement of the skewed T-cell
      repertoire was not seen until 2 years of treatment. It consisted of disappearance
      of oligoclonal subpopulations and (polyclonal) reappearance of absent TCRBV gene
      families. The RT-PCR results were correlated with the TCRBV protein expression
      using TCRBV-specific monoclonal antibodies. T lymphocytes from four patients with
      active HCL contained large expansions of particular TCRBV-expressing cells (up to
      25% of the CD3+ cells; 600 to 700/microL whole blood), which decreased during IFN
      alpha therapy in both patients tested. Finally, restoration of the TCR repertoire
      matched normalization of the functional immune repertoire as measured by
      proliferative, helper, and cytotoxic T-lymphocyte precursor frequencies against
      major histocompatibility complex-unrelated individuals. In conclusion,
      oligoclonal bands of TCRBV gene families found by RT-PCR correspond with a
      dramatic increase in circulating T lymphocytes expressing the same TCRBV family.
      Moreover, IFN-alpha can restore the skewed T-cell repertoire and suppress
      persistent T-cell clones upon treatment of the accompanying malignancy.

PMID- 9596671
TI  - T-Cell receptor signaling pathway exerts a negative control on thrombin-mediated
      increase in [Ca2+]i and p38 MAPK activation in Jurkat T cells: implication of the
      tyrosine kinase p56Lck.
AB  - Activation of the mitogen-activated protein kinase (Erk) and c-Jun terminal
      kinase is a well-documented mechanism for the seven transmembrane spanning
      receptors. We have previously shown that thrombin stimulation of the T-leukemic
      cell line Jurkat induced a transient increase in [Ca2+]i and tyrosine
      phosphorylation of several cellular proteins. Here, we have analyzed p42-44 MAPK,
      JNK and p38 MAPK activation using Jurkat T-cell lines deficient in either the
      tyrosine kinase p56Lck (JCaM1) or the tyrosine phosphatase CD45 (J45.01). Our
      results demonstrate that p56Lck and CD45 exert a negative control on thrombin
      induced p38 MAPK activation and [Ca2+]i release in Jurkat cells. Thrombin
      receptor expression was identical on the different cell lines as assessed by FACS
      analysis. Tyrosine phosphorylation of p38 MAPK was drastically increased after
      thrombin stimulation of JCaM1 or J45.01 cells, as compared with parental cells
      (JE6.1). P42-44 MAPK and JNK activity also enhanced after thrombin treatment of
      JE6.1 and JCaM1 cell lines, whereas basal kinase activity was higher in J45.01
      cells and was not further stimulated by thrombin. Thrombin and thrombin receptor
      agonist peptide-induced [Ca2+]i mobilization paralleled p38 MAPK activation in
      JCaM1 and J45.01 cells. Moreover, reconstitution of J45.01 and JCaM1 cell lines
      with either CD45 or Lck is accompanied by restoration of a normal thrombin
      induced [Ca2+]i response and p38MAPK phosphorylation. These data show that a
      component of the T-cell receptor signaling pathway exerts a negative control on
      thrombin-induced responses in Jurkat T cells. Accordingly, we found that thrombin
      enhanced tyrosine phosphorylation of p56Lck and decreased p56Lck kinase activity
      in J45.01 cells. Our results are consistent with a negative role for p56Lck on
      thrombin-induced [Ca2+]i release and p38 MAPK activation in Jurkat T-cell lines.

PMID- 9596672
TI  - Characterization of a novel CC chemokine, HCC-4, whose expression is increased by
      interleukin-10.
AB  - We have identified and characterized a human beta (CC) chemokine, designated HCC
      4, that is most closely related to HCC-1 and which demonstrates chemotactic
      activity for monocytes. Northern analysis of multiple tissue blots and of
      activated monocytes mRNA shows expression of a 500-bp mRNA. A 1,500-bp mRNA was
      highly expressed in monocytes activated 12 hours in the presence of interleukin
      10 (IL-10) but was absent in monocytes activated for only 1 hour regardless of
      the presence or absence of IL-10. The upregulation of expression in the presence
      of IL-10 is in contrast to the downregulatory effects of IL-10 on expression of
      most other chemokines. Recombinant HCC-4 demonstrated chemotactic activity for
      human monocytes and THP-1 monocyte cells but not for resting lymphocytes or
      neutrophils. HCC-4 also induced a Ca2+ flux in THP-1 cells that was desensitized
      by prior exposure to RANTES. Taken together, these data indicate that HCC-4 is a
      novel chemokine whose expression is uniquely upregulated by IL-10.

PMID- 9596673
TI  - Viral superantigen-induced negative selection of TCR transgenic CD4+ CD8+
      thymocytes depends on activation, but not proliferation.
AB  - T-cell negative selection, a process by which intrathymic immunological tolerance
      is induced, involves the apoptosis-mediated clonal deletion of potentially
      autoreactive T cells. Although different experimental approaches suggest that
      this process is triggered as the result of activation-mediated cell death, the
      signal transduction pathways underlying this process is not fully understood. In
      the present report we have used an in vitro system to analyze the cell activation
      and proliferation requirements for the deletion of viral superantigen (SAg)
      reactive Vbeta8.1 T-cell receptor (TCR) transgenic (TG) thymocytes. Our results
      indicate that in vitro negative selection of viral SAg-reactive CD4+ CD8+
      thymocytes is dependent on thymocyte activation but does not require the
      proliferation of the negatively signaled thymocytes.

PMID- 9596674
TI  - Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in
      vitro.
AB  - Antigen-presenting cells are thought to modulate the development of Th1 and Th2
      cells by the secretion of interleukin-10 (IL-10) and IL-12. Because
      glucocorticoids (GC) favor the development of Th2 responses, we determined
      whether dexamethasone (DEX) and hydrocortisone (HC) have differential effects on
      lipopolysaccharide-induced IL-10 and IL-12 production in whole-blood cultures.
      Significant inhibition of IL-12(p40) and IL-12(p70) was found with 10(-8) mol/L
      and 10(-9) mol/L DEX respectively, whereas IL-10 was relatively insensitive or
      even stimulated. Accordingly, the expression of IL-12(p40) and IL-12(p35) mRNA
      was more sensitive to DEX than IL-10 mRNA. The glucocorticoid receptor (GR)
      antagonist RU486 enhanced IL-12 production and largely abrogated the inhibition
      of IL-12 by GC, indicating that this suppression was mainly GR-mediated. High
      concentrations of RU486 were inhibitory for IL-10, suggesting that GC may exert a
      positive effect on IL-10. In the presence of neutralizing anti-IL-10 antibodies,
      DEX was still capable of IL-12 suppression whereas RU486 still enhanced IL-12
      production, indicating that GC do not modulate IL-12 via IL-10 exclusively. Taken
      together these results indicate that GC may favor Th2 development by differential
      regulation of IL-10 and IL-12.

PMID- 9596675
TI  - Interleukin-15 (IL-15) can replace the IL-2 signal in IL-2-dependent adult T-cell
      leukemia (ATL) cell lines: expression of IL-15 receptor alpha on ATL cells.
AB  - Interleukin-15 receptor (IL-15R) and IL-2R have the same beta and gamma chains,
      but IL-15R has a specific alpha chain distinct from that of IL-2Ralpha, which is
      indispensable for the high affinity binding of IL-15. In the present study, we
      examined four IL-2-dependent adult T-cell leukemia (ATL) cell lines for their IL
      15R expression. All cell lines bound IL-15, which was not inhibited by a 100-fold
      excess amount of IL-2, proliferated in response to IL-15 to the same degree as to
      the stimulation with IL-2, and were maintained without IL-2. The responses to 1L
      15 were inhibited by the antibodies against IL-2R beta or gamma chains but was
      not by the IL-2R alpha chain antibody. [125I]-IL-15 exhibited a single high
      affinity binding with an apparent kd of 0.17 nmol/L. Reverse transcription
      coupled polymerase chain reaction (RT-PCR) showed that the cell lines had the
      mRNA of IL-15R alpha. The cell lines also had IL-15 mRNA. Despite the presence of
      IL-15 mRNA, the cell lines did not secrete IL-15, and the culture supernatants of
      fresh ATL cells and plasma from the patients did not contain a detectable amount
      of IL-15 with a few exceptional cases, although fresh ATL cells also responded to
      IL-15. These results suggest that ATL cells have the complete form of IL-15R and
      respond to IL-15. Such an IL-15-dependent cell proliferation mechanism might be
      used in the development of ATL and for the invasion and proliferation of ATL
      cells in the visceral organs.

PMID- 9596676
TI  - Differential sensitivity of CD4+ and CD8+ T lymphocytes to the killing efficacy
      of Fas (Apo-1/CD95) ligand+ tumor cells in B chronic lymphocytic leukemia.
AB  - B-chronic lymphocytic leukemia (B-CLL) is characterized by cellular and humoral
      immune defects resulting in increased rates of infection and disturbed immune
      surveillance against cancer cells as well as by the expansion of slowly
      proliferating tumor cells. We found increased Fas receptor (FasR) expression in
      peripheral blood CD4+ and CD8+ cells of B-CLL patients compared with the
      equivalent cells of healthy donors. Although increased Fas receptor expression
      was significant in both T-lymphocytic subsets, only CD4+ cells from B-CLL
      patients underwent apoptosis after treatment with the agonistic Fas antibody
      CH11. In CD4+ cells of B-CLL patients, the Fas-sensitivity also correlated with a
      CD4+/CD8+ ratio below the lower threshold of healthy individuals (<1.0). By
      contrast, FasR expression in the CD19(+) fraction of B-CLL patients was
      downregulated compared with normal controls, and this was associated with an
      insensitivity to CH11-induced apoptosis. The B-CLL cell line EHEB as well as
      CD19(+) cells from B-CLL patients constitutively expressed Fas ligand (FasL). The
      FasL was functionally active, as the B-CLL cell line as well as T-cell-depleted
      CD19+ B-CLL fractions were able to kill target T-acute lymphatic leukemia (T-ALL)
      cells in vitro. This effect was inhibited by the antagonistic FasR-antibody ZB4,
      the neutralizing anti-FasL monoclonal antibody (MoAb) NOK-2 or by transfection of
      the caspase inhibitor crmA. These data point to the fact that expression of FasL
      on CD19(+) B-CLL cells, together with enhanced susceptibility of CD4+ T cells
      toward FasL-bearing effector cells, are causally linked to the relative reduction
      of CD4+ cells occurring during B-CLL progression. These findings could explain
      the inversion of the ratio of CD4+/CD8+ cell numbers, which may be causally
      linked to the immune deficiency observed in these patients and to the expansion
      of the neoplastic clone in B-CLL.

PMID- 9596677
TI  - A directly spliced exon 10-containing CD44 variant promotes the metastasis and
      homotypic aggregation of aggressive non-Hodgkin's lymphoma.
AB  - Variants of the CD44 cell-surface adhesion molecule include additional sequences
      encoded by combinations of exons from the membrane proximal domain (exons 6-14).
      Preliminary studies suggest that these additional variable membrane proximal
      sequences may alter the ligand specificity, glycosylation, and biologic function
      of CD44. In earlier studies, we found that primary extranodal and widely
      disseminated aggressive non-Hodgkin's lymphomas (NHLs) and normal activated B
      cells expressed a directly spliced exon 10-containing variant (CD44ex10), whereas
      normal resting B cells expressed larger exon 10-containing variants (CD44ex10-14
      and CD44ex7-14). To obtain additional information regarding the function of exon
      10-containing CD44 variants in aggressive NHL, we generated aggressive NHL
      transfectants that expressed CD44ex10, CD44ex10-14, CD44ex7-14, the standard CD44
      isoform (CD44H), or vector alone, and evaluated the local tumorogenicity,
      aggregation, and metastatic potential of these transfectants. CD44ex10 aggressive
      NHL transfectants were more likely to cause local tumor formation in nude mice
      than transfectants expressing the larger exon 10-containing variants, CD44H, or
      vector alone. In addition, cell suspensions derived from CD44ex10 local tumors
      exhibited far greater homotypic aggregation than those obtained from other CD44
      or vector-only local tumors. In nude mice that received CD44ex10 transfectants,
      distant metastases were also significantly more likely to develop than in animals
      that were given either the CD44ex10-14, CD44ex7-14, CD44H, or vector-only
      transfectants. These data provide the first evidence that the directly spliced
      exon 10-containing CD44 variant (CD44ex10) has a unique biologic function in
      aggressive NHL.

PMID- 9596678
TI  - Analysis of VH genes in follicular and diffuse lymphoma shows ongoing somatic
      mutation and multiple isotype transcripts in early disease with changes during
      disease progression.
AB  - Investigations of VH gene mutational patterns in B-cell tumors are often
      performed at an arbitrary time point of disease. To assess the effects of disease
      progression, tumor-derived VH genes have been monitored from presentation through
      treatment and relapse in one patient with follicle center lymphoma (FCL), and two
      patients with primary diffuse large B-cell lymphoma (DLCL). The patient with FCL
      and one patient with DLCL both achieved clinical remission, although this was
      only partial in the FCL. However, both subsequently relapsed, and the second
      patient with DLCL was refractory to radiotherapy and chemotherapy. In each case,
      the tumor-derived VH sequence was identified, and the CDR3 "clonal signature" was
      used to track tumor cell sequences in subsequent biopsies. All cases showed
      somatic mutations, with intraclonal heterogeneity evident at presentation, and
      some sequences were aberrant. The VH sequences of the DLCL which responded to
      treatment became homogeneous at relapse. The sequences of both the FCL and the
      refractory DLCL remained heterogeneous. In all cases, transcripts of multiple Ig
      isotypes could be identified, and there was immunophenotypic evidence for
      expression of several Ig isotypes. The case of refractory DLCL had identifiable
      transcripts from IgM, IgD, IgA, IgG, and IgE, but appeared to lose the ability to
      produce alternative isotype transcripts and protein at the late stage of disease.
      These cases indicate that VH gene analysis can be used to probe tumor cell
      behavior in cases of lymphoma and that perturbations caused by therapy and
      disease progression can occur.

PMID- 9596679
TI  - Combined arsenic and retinoic acid treatment enhances differentiation and
      apoptosis in arsenic-resistant NB4 cells.
AB  - In the acute promyelocytic leukemia (APL) cell line NB4, as well as in APL
      patients' cells, arsenic trioxide (As2O3) leads to incomplete cell maturation,
      induction of apoptosis, as well as to the degradation of the oncogenic
      PML/RARalpha fusion protein. We have isolated an arsenic-resistant NB4 subline
      (NB4-AsR), which fails to undergo apoptosis, but maintains the partial
      differentiation response to this drug. When grown in the presence of As2O3, NB4
      AsR cells degrade PML/RARalpha, slightly differentiate, and become more sensitive
      to serum deprivation-induced apoptosis. Similarly, in RA-resistant NB4-R1 cells,
      RA induced a significant PML/RARalpha degradation and yet failed to induce cell
      maturation. Thus, As2O3- or retinoic acid (RA)-induced PML/RARalpha degradation
      may be a prerequisite, but is not sufficient for the full
      differentiative/apoptotic response to these drugs. Strikingly, RA-triggered
      differentiation and apoptosis were greatly accelerated in As2O3-treated NB4-AsR
      cells. The synergism between these two agents in this setting could provide an
      experimental basis for combined or sequential RA/As2O3 therapies.

PMID- 9596680
TI  - Caspase activation is required for nitric oxide-mediated, CD95(APO-1/Fas)
      dependent and independent apoptosis in human neoplastic lymphoid cells.
AB  - Nitric oxide (NO), an important effector molecule involved in immune regulation
      and host defense, was shown to induce apoptosis in lymphoma cells. In the present
      report the NO donor glycerol trinitrate was found to induce apoptosis in Jurkat
      cells that are sensitive to CD95-mediated kill. In contrast, a CD95-resistant
      Jurkat subclone showed substantial protection from apoptosis after exposure to
      NO. NO induced mRNA expression of CD95 (APO-1/Fas) and TRAIL/APO-2 ligands.
      Moreover, NO triggered apoptosis in freshly isolated human leukemic lymphocytes
      which were also sensitive to anti-CD95 treatment. The ability of NO to induce
      apoptosis was completely blocked by a broad-spectrum ICE (interleukin-1beta
      converting enzyme)-protease/caspase inhibitor and correlated with FLICE/caspase-8
      activation. This activation was abrogated in some neoplastic lymphoid cells but
      not in others by the inhibitor of protein synthesis cycloheximide. Our results
      were confirmed using an in vitro experimental model of coculture of human
      lymphoid target cells with activated bovine endothelial cells generating NO as
      effectors. Furthermore, the inhibition of endogenous NO production with the
      inducible NO synthase inhibitor NG-monomethyl-L-arginine caused a complete
      abrogation of the apoptotic effect. Our data provide evidence that NO-induced
      apoptosis in human neoplastic lymphoid cells strictly requires activation of
      caspases, in particular FLICE, the most CD95 receptor-proximal caspase. Depending
      on the cell line tested this activation required or was independent of the CD95
      receptor/ligand system.

PMID- 9596681
TI  - Characteristic pattern of chromosomal gains and losses in primary large B-cell
      lymphomas of the gastrointestinal tract.
AB  - In contrast to low-grade B-cell lymphomas originating in the gastrointestinal
      (GI) tract, only few cytogenetic data are available for the large cell, highly
      malignant variants. We studied 31 large B-cell lymphomas of the GI tract by
      comparative genomic hybridization (CGH) and fluorescence in situ hybridization
      using specific DNA probes (FISH). The most frequent aberrations were gains of all
      or of parts of chromosomes 11 (11 cases), 12 (9 cases), 1q (4 cases), and 3q (4
      cases). Losses of parts of chromosome 6q and of parts of the short arm of
      chromosome 17 (6 cases each) were found most frequently. In four cases a total of
      seven high-level DNA amplifications was detected. In two of these cases,
      involvement of specific protooncogenes (REL and MYC) was shown. Some genetic
      aberrations seemed to be associated with an inferior clinical course: patients
      with >/=2 aberrations had a significantly shorter median survival. Furthermore,
      all patients with gains of all or parts of chromosome arm 1q and with high-level
      DNA amplifications as well as seven of nine patients with gains of all or parts
      of chromosome 12 died of lymphoma. In conclusion, the pattern of chromosomal
      gains and losses in large B-cell lymphomas was different from data reported for
      low-grade (MALT) lymphomas of the stomach and bowel, especially with respect to
      the high incidence of partial gains of chromosome arm 11q and of all or parts of
      chromosome 12 and the low frequency of polysomy 3. In addition, our data suggest
      that chromosomal gains and losses detected by CGH and FISH may predict for the
      outcome of patients with this tumor entity.

PMID- 9596682
TI  - Isolation of tumor-specific cytotoxic CD4+ and CD4+CD8dim+ T-cell clones
      infiltrating a cutaneous T-cell lymphoma.
AB  - We have isolated several T-cell clones from lymphocytes infiltrating a human
      major histocompatibility class (MHC) II negative cutaneous T-cell lymphoma
      (CTCL). We describe here two of these clones, TC5 and TC7, with, respectively, a
      CD4(+)CD8dim+ and CD4(+)CD8(-) phenotype. Both clones mediated a specific MHC
      class I-restricted cytotoxic activity toward the fresh autologous tumor cells,
      and autologous tumor cell lines previously established with interleukin-2 (IL-2)
      and IL-7 from the skin and from the blood. Analysis of the T-cell receptor (TCR)
      Vbeta gene expression showed that the tumor cells, which were shown to have a
      trisomy 7 by fluorescent in situ hybridization, expressed Vbeta7/Jbeta2.3,
      Vbeta13/Jbeta2.5, and Vbeta22/Jbeta2.5 rearrangements. Phenotypic analysis using
      specific anti-Vbeta monoclonal antibodies indicated that only Vbeta13 could be
      detected on the cell membrane of the tumor cells. Analysis of the TCR Vbeta gene
      expression of the clones showed that TC5 and TC7 expressed a unique TCR-Vbeta
      transcript, corresponding, respectively, to Vbeta5/Jbeta2.3 and Vbeta17/Jbeta2.7
      gene segments. To determine whether these reactive T lymphocytes were present in
      vivo, we used specific primers corresponding to TC5- and TC7-Vbeta TCR
      transcripts. The results showed that both cytotoxic T-cell clones were present at
      the lesional skin site and amplified in vitro. TC7 was found in the patient
      peripheral blood invaded by tumoral cells, whereas TC5 was not, indicating that
      the repertoire of the reactional lymphocytes differs in the blood and at the
      tumor site. These results show for the first time the presence of reactive T
      lymphocytes with CD4 or double-positive phenotype infiltrating a CTCL. These
      findings raise the question of the role of these antitumoral effector T cells in
      the tumor growth.

PMID- 9596684
TI  - Increases in neutral, Mg2+-dependent and acidic, Mg2+-independent
      sphingomyelinase activities precede commitment to apoptosis and are not a
      consequence of caspase 3-like activity in Molt-4 cells in response to thymidylate
      synthase inhibition by GW1843.
AB  - Thymidylate synthase (TS) inhibition causes cell death, and this enzyme is the
      target for the important chemotherapy regime 5-fluorouracil/leucovorin. GW1843
      (1843U89) is a potent and specific folate analog TS inhibitor in clinical
      development. Because of the importance of TS as a chemotherapy target, we are
      studying the mechanism of TS inhibition-induced cell death by GW1843. Ceramide is
      a regulatory lipid generated by the action of sphingomyelinase and is believed to
      signal apoptosis. The role of the ceramide in apoptotic signaling was studied in
      Molt-4 human T-cell leukemia cells undergoing cell death after treatment with
      GW1843. In response to GW1843, Molt-4 cells undergo apoptosis with both acidic
      pH, Mg2+-independent sphingomyelinase (ASMase) and neutral pH, Mg2+-dependent
      sphingomyelinase (NSMase) activities elevated as early steps in the initiation of
      apoptosis before Molt-4 commitment to death. These activities lead to ceramide
      production with kinetics consistent with a role as an effector molecule signaling
      the initiation of apoptosis in Molt-4 cells. These changes were found to be
      independent of caspase 3-like (CPP32/apopain) activity and DNA degradation, but
      were not separable from membrane blebbing or cell lysis in this cell line. In
      this report, kinetic evidence is provided for a role of ceramide in initiating
      GW1843-induced cell death of Molt-4 T-cell leukemia cells.

PMID- 9596683
TI  - p53 expression in B-cell chronic lymphocytic leukemia: a marker of disease
      progression and poor prognosis.
AB  - We have analyzed by immunocytochemistry (ICC) the frequency of p53 protein
      expression in 181 cases of B-cell chronic lymphocytic leukemia (CLL) followed at
      a single institution to assess the relationship between p53 and the clinical and
      morphological features of the disease, as well as the possible involvement of
      this protein in the pathogenesis of the more aggressive forms of CLL. The overall
      frequency of p53 protein positivity in CLL was 15% (27 of 181 cases). There were
      no significant differences in age, sex, absolute lymphocyte count, or lymphocyte
      doubling time between p53-positive and -negative patients. By contrast, p53
      positive patients had a significantly higher percentage of prolymphocytes (P =
      .002) and a significantly lower percentage of residual CD3-positive T lymphocytes
      (P = .0001). No correlation was found between the percentage of p53-positive
      cells and the percentage of cells in cycle assessed by the monoclonal antibody Ki
      67. When the percentage of p53 positivity was correlated with the clinical stage
      of the disease, the proportion of p53-positive cases increased significantly from
      Binet's stage A (8 of 108; 7.4%), to stage B (12 of 49; 24.4%) and C (7 of 24;
      29.2%) (P = .002). p53 positivity correlated also with the phase of the disease,
      showing a low expression at diagnosis (8 of 112; 7.1%) and a significantly higher
      expression in patients studied during the course of the disease (7 of 35; 20%)
      and, to a further extent, with disease progression (12 of 34; 35.3%) (P = .0001).
      The association of p53 protein expression with mutations in the gene was
      confirmed by direct sequence of the entire cDNA in 15 of the 17 ICC positive
      cases tested (88%). A significantly shorter treatment-free interval from
      diagnosis (P = .003) and a poorer response to therapy (P = .007) was observed in
      p53-positive compared with p53-negative patients. Overall survival from the time
      of diagnosis, as well as from the time of p53 protein analysis, was significantly
      shorter in patients with p53 protein expression (P = .03 and .0001,
      respectively). Moreover, in multivariate analysis, p53 expression and stage C
      were independently associated with a short survival. The results of this study
      indicate that in CLL the expression of the p53 protein, analyzed by a simple and
      reliable immunocytochemical method, is strongly associated with p53 gene
      mutations, a morphological variant (CLL with >10% prolymphocytes), advanced
      clinical stage, progressive disease, poor response to therapy, and short
      survival.

PMID- 9596685
TI  - A large deletion within the protein 4.1 gene associated with a stable truncated
      mRNA and an unaltered tissue-specific alternative splicing.
AB  - Protein 4.1 is a major protein of the red blood cell skeleton. It binds to the
      membrane through its 30-kD N-terminal domain and to the spectrin-actin lattice
      through its 10-kD domain. We describe here the molecular basis of a heterozygous
      hereditary elliptocytosis (HE) associated with protein 4.1 partial deficiency.
      The responsible allele displayed a greater than 70-kb genomic deletion, beginning
      within intron 1 and ending within a 1.3-kb region upstream from exon 13. This
      deletion encompassed both erythroid and nonerythroid translation initiation
      sites. It accounts for the largest deletion known in genes encoding proteins of
      the red blood cell membrane. The corresponding mRNA was shortened by 1727 bases,
      due to the absence of exons 2 to 12. Nevertheless, this mRNA was stable. It
      showed a similar pattern in lymphoblastoid cells as in reticulocytes.
      Differential splicing of exons within the undeleted region remained regulated in
      a tissue-specific manner. Exons 14, 15, and 17a were absent from both
      reticulocyte and lymphocyte mRNAs, whereas exon 16 was present in reticulocytes
      but absent from lymphocytes. Thus, differential splicing on a local scale was not
      dependent on the overall structure of protein 4.1 mRNA in this particular
      instance.

PMID- 9596686
TI  - Biliary iron excretion in rats following treatment with analogs of pyridoxal
      isonicotinoyl hydrazone.
AB  - Iron overload is a major life-threatening complication of thalassemia major and
      other iron-loading anemias treated by regular blood transfusions. Although the
      clinical manifestations of iron overload may be prevented by desferrioxamine, the
      only iron-chelating drug in routine clinical use, this treatment requires
      subcutaneous infusion of desferrioxamine for 12 hours each day. New orally
      effective iron chelators are urgently needed, and pyridoxal isonicotinoyl
      hydrazone (PIH), which was first recognized as an effective iron chelator in
      vitro and subsequently in vivo, shows promise for the treatment of iron overload.
      More recently, over 40 analogs of PIH were synthesized, and some of them proved
      to be very potent in mobilizing 59Fe in vitro from 59Fe-labeled cells. In this
      study, we show that PIH analogs such as pyridoxal benzoyl hydrazone, pyridoxal p
      methoxybenzoyl hydrazone (PMBH), pyridoxal m-fluorobenzoyl hydrazone (PFBH), and
      pyridoxal-2-thiophenecarboxyl hydrazone, compounds previously shown to mobilize
      iron from cells in vitro, are also effective in vivo. All of these chelators
      significantly enhanced biliary excretion of iron (measured by atomic absorption
      spectrophotometry) following their intraperitoneal (IP) and/or oral
      administration to rats. The most effective was PFBH, which increased iron
      concentration in the bile about 150-fold, as compared with basal biliary iron
      concentration, within 1 hour following a single IP dose of 0.2 mmol/kg body
      weight. In contrast, desferrioxamine increased the biliary iron concentration
      only 20-fold to 30-fold under the same conditions. Moreover, while control rats
      excreted approximately 0.8 microg Fe in 2 hours, treatment with PFBH, PMBH, and
      desferrioxamine resulted in cumulative excretions of 87, 59, and 22 microg Fe,
      respectively, in the same period of time. Interestingly, PMBH was also quite
      effective following gastric administration, resulting in a 6-hour cumulative
      value of 34 microg Fe. These compounds are nontoxic and are inexpensive and easy
      to make. Their further evaluation as candidate drugs for the treatment of iron
      overload is warranted.

PMID- 9596687
TI  - The efficacy of reducing agents or antioxidants in blocking the formation of
      dense cells and irreversibly sickled cells in vitro.
AB  - We show that N-acetylcysteine (NAC) has the ability to cause statistically
      significant diminishment in the in vitro formation of irreversibly sickled cells
      (ISCs) at concentrations greater than 250 micromol/L. Other antioxidants,
      approved for human use (cysteamine, succimer, dimercaprol), were not efficacious.
      NAC had the ability to cause statistically significant conversion of ISCs formed
      in vivo back to the biconcave shape. NAC was also shown to reduce the formation
      of dense cells and increase the available thiols in beta-actin. We showed that
      diminishing reduced glutathione (GSH), by treatment with 1-chloro-2,4
      dinitrobenzene, resulted in increased dense cells. We conclude the NAC blocks
      dense cell formation and ISC formation by targeting channels involved in cellular
      dehydration and beta-actin, respectively. The efficacy of NAC is probably due to
      its combined antioxidant activity and ability to increase intracellular GSH.

PMID- 9596688
TI  - Molecular chaperone GRP94 binds to the Fanconi anemia group C protein and
      regulates its intracellular expression.
AB  - The FAC protein encoded by the gene defective in Fanconi anemia (FA)
      complementation group C binds to at least three ubiquitous cytoplasmic proteins
      in vitro. We used here the complete coding sequence of FAC in a yeast two-hybrid
      screen to identify interacting proteins. The molecular chaperone GRP94 was
      isolated twice from a B-lymphocyte cDNA library. Binding was confirmed by
      coimmunoprecipitation of FAC and GRP94 from cytosolic, but not nuclear, lysates
      of transfected COS-1 cells, as well as from mouse liver cytoplasmic extracts.
      Deletion mutants of FAC showed that residues 103-308 were required for
      interaction with GRP94, and a natural splicing mutation within the IVS-4 of FAC
      that removes residues 111-148 failed to bind GRP94. Ribozyme-mediated
      inactivation of GRP94 in the rat NRK cell line led to significantly reduced
      levels of immunoreactive FAC and concomitant hypersensitivity to mitomycin C,
      similar to the cellular phenotype of FA. Our results demonstrate that GRP94
      interacts with FAC both in vitro and in vivo and regulates its intracellular
      level in a cell culture model. In addition, the pathogenicity of the IVS-4
      splicing mutation in the FAC gene may be mediated in part by its inability to
      bind to GRP94.

PMID- 9596689
TI  - Erythropoietin prevents the development of interleukin-12-induced anemia and
      thrombocytopenia but does not decrease its antitumor activity in mice.

PMID- 9596690
TI  - Alterations of the MMAC1/PTEN gene in lymphoid malignancies.

PMID- 9596691
TI  - A response to AC133 hematopoietic stem cell antigen: human homologue of mouse
      kidney prominin or distinct member of a novel protein family?

PMID- 9596692
TI  - Multiple myeloma and HHV8 infection.

PMID- 9596693
TI  - Detection of human herpesvirus-8 DNA in bone marrow biopsies from patients with
      multiple myeloma and Waldenstrom's macroglobulinemia.

PMID- 9596694
TI  - Pancytopenia secondary to oxalosis in a 23-year-old woman.

PMID- 9596695
TI  - Bacterial perturbation of cytokine networks.

PMID- 9596696
TI  - Cytochalasin-induced actin disruption of polarized enterocytes can augment
      internalization of bacteria.
AB  - Cytochalasin-induced actin disruption has often been associated with decreased
      bacterial internalization by cultured epithelial cells, although polarized
      enterocytes have not been systematically studied. In assays using confluent
      polarized HT-29 enterocytes, cytochalasin D appeared to increase internalization
      of wild-type Salmonella typhimurium, Proteus mirabilis, and Escherichia coli.
      HeLa and HEp-2 epithelial cells, as well as HT-29 and Caco-2 enterocytes, were
      used to clarify this unexpected observation. Resulting data showed that
      cytochalasin D was associated with increased internalization of S. typhimurium
      and P. mirabilis by both HT-29 and Caco-2 enterocytes and with increased
      internalization of E. coli by HT-29 enterocytes; with either HeLa or HEp-2 cells,
      cytochalasin was associated with no change or a decrease in internalization of
      these same bacterial strains. Cytochalasin caused decreased internalization of
      Listeria monocytogenes by HT-29, Caco-2, HeLa, and HEp-2 cells, indicating that
      cytochalasin did not consistently augment bacterial internalization by polarized
      enterocytes. Fluorescein-labeled phalloidin confirmed marked disruption of
      filamentous actin in cytochalasin-treated HT-29, Caco-2, HeLa, and HEp-2 cells.
      Cytochalasin had no noticeable effect on epithelial viability but caused
      distorted apical microvilli, cell rounding, and separation of adjacent
      enterocytes in confluent cultures (with a corresponding decrease in
      transepithelial electrical resistance). Scanning electron microscopy showed that
      cytochalasin-induced enhanced bacterial internalization was associated with
      preferential bacterial adherence on the exposed enterocyte lateral surface.
      Colchicine, used to disrupt microtubules, had no noticeable effect on bacterial
      internalization by HT-29 or Caco-2 enterocytes. These data indicated that for HT
      29 and Caco-2 enterocytes, cytochalasin-induced disruption of filamentous actin
      might augment internalization of some bacterial species by a mechanism that
      appeared to involve exposure of the enterocyte lateral surface.

PMID- 9596697
TI  - Biophysical characterization of the stability of the 150-kilodalton botulinum
      toxin, the nontoxic component, and the 900-kilodalton botulinum toxin complex
      species.
AB  - Botulinum neurotoxin serotype A is initially released from the bacterium
      Clostridium botulinum as a stable 900-kDa complex. The serotype A 900-kDa complex
      is one of the forms of the toxin being used as a therapeutic agent for the
      treatment of various neuromuscular disorders. Previous experiments have
      demonstrated that the 900-kDa complex form of the toxin protects the toxin from
      the harsh conditions of the gastrointestinal tract. To provide molecular level
      details of the stability and equilibrium of the 900-kDa complex, the nontoxic
      component, and the toxic (botulinum neurotoxin) component, the three species have
      been investigated with a series of biophysical techniques at the molecular level
      (dynamic light scattering, proteolysis, circular dichroism, pH incubations, and
      agglutination assays). These experiments were conducted under harsh conditions
      which mimic those found along the gastrointestinal tract. Separately, exposure to
      denaturing and proteolytic conditions degrades both the botulinum neurotoxin and
      the nontoxic component. In the 900-kDa complex, the botulinum neurotoxin is
      protected during exposure to the gastrointestinal environment and the nontoxic
      component is slightly modified. Surprisingly, the toxin protects the ability of
      the nontoxic component to agglutinate erythrocytes. Contrary to previous reports,
      the purified 900-kDa complex did not have agglutination ability until after
      exposure to the proteolytic conditions. These experiments provide new evidence
      and detail for the theory that the nontoxic component and the toxic component
      protect one another during exposure to harsh conditions, and a molecular model is
      presented for the passage of the toxin through the gastrointestinal tract.

PMID- 9596698
TI  - Differential gene expression in response to adjunctive recombinant human
      interleukin-2 immunotherapy in multidrug-resistant tuberculosis patients.
AB  - Administration of low-dose recombinant human interleukin 2 (rhuIL-2) in
      combination with multidrug chemotherapy to patients with multidrug-resistant
      tuberculosis (MDR TB) induces measurable changes in in vitro immune response
      parameters which are associated with changes in the clinical and bacteriologic
      status of the patients. To determine the molecular basis of these changes, we
      have used semiquantitative reverse transcriptase-initiated PCR (RT-PCR) and
      differential display technology. During rhuIL-2 treatment of MDR TB patients,
      decreased levels of gamma interferon (IFN-gamma) mRNA in peripheral blood
      mononuclear cells (PBMC) relative to baseline levels were observed. However, at
      the site of a delayed-type hypersensitivity (DTH) response to purified protein
      derivative of tuberculin (PPD), the expression of cellular IFN-gamma and IL-2
      mRNAs was increased during rhuIL-2 therapy. Levels of other cytokine mRNAs were
      not significantly affected by rhuIL-2 administration. Using differential-display
      RT-PCR, we identified several genes expressed at the DTH skin test site which
      were up- or down-regulated during rhuIL-2 treatment. Cytochrome oxidase type I
      mRNA was increased in response to rhuIL-2 therapy relative to baseline levels, as
      was heterogeneous nuclear ribonuclear protein G mRNA. CD63, clathrin heavy chain,
      and beta-adaptin mRNAs, all of which encode proteins associated with the
      endocytic vacuolar pathway of cells, were also differentially regulated by rhuIL
      2 administration. The differential effects of IL-2 were confirmed in vitro by
      using PBMC obtained from PPD-positive individuals stimulated with Mycobacterium
      tuberculosis and IL-2. The differential expression of genes may provide a
      surrogate marker for leukocyte activation at a mycobacterial antigen-specific
      response site and for the development of an enhanced antimicrobial response which
      may result in improved outcomes in MDR TB patients.

PMID- 9596699
TI  - Structure-function relationship of antibacterial synthetic peptides homologous to
      a helical surface region on human lactoferrin against Escherichia coli serotype
      O111.
AB  - Lactoferricin includes an 11-amino-acid amphipathic alpha-helical region which is
      exhibited on the outer surface of the amino-terminal lobe of lactoferrin.
      Synthetic peptides homologous to this region exhibited potent antibacterial
      activity against a selected range of both gram-negative and gram-positive
      bacteria. An analog synthesized with methionine substituted for proline at
      position 26, which is predicted to disrupt the helical region, abolished
      antibacterial activity against Escherichia coli and considerably reduced
      antibacterial activity against Staphylococcus aureus and an Acinetobacter strain.
      The mode of action of human lactoferrin peptide (HLP) 2 against E. coli serotype
      O111 (NCTC 8007) was established by using flow cytometry, surface plasmon
      resonance, and transmission electron microscopy. Flow cytometry was used to
      monitor membrane potential, membrane integrity, and metabolic processes by using
      the fluorescent probes bis-1,3-(dibutylbarbituric acid)-trimethine oxonol,
      propidium iodide, and carbonyl cyanide m-chlorophenylhydrazone, respectively. HLP
      2 was found to act at the cell membrane, causing complete loss of membrane
      potential after 10 min and of membrane integrity within 30 min, with irreversible
      damage to the cell as shown by rapid loss of viability. The number of particles,
      measured by light scatter on the flow cytometer, dropped significantly, showing
      that bacterial lysis resulted. The peptide was shown to bind to E. coli O111
      lipopolysaccharide by using surface plasmon resonance. Transmission electron
      microscopy revealed bacterial distortion, with the outer membrane becoming
      detached from the inner cytoplasmic membrane. We conclude that HLP 2 causes
      membrane disruption of the outer membrane, resulting in lysis, and that
      structural considerations are important for antibacterial activity.

PMID- 9596700
TI  - Streptococcus pneumoniae type 14 polysaccharide-conjugate vaccines: length
      stabilization of opsonophagocytic conformational polysaccharide epitopes.
AB  - A simple and convenient method was developed for the preparation of Streptococcus
      pneumoniae type 14 polysaccharide (Pn14PS)-tetanus toxoid (TT) conjugate
      vaccines, using terminally linked Pn14PS fragments of different lengths. Native
      Pn14PS was simultaneously depolymerized and activated for conjugation by partial
      N-deacetylation followed by nitrous acid deamination which yielded fragments (1.4
      to 150.0 kDa) having a free aldehyde at the reducing end. These were then
      conjugated to TT through their terminal aldehydic groups, using the reductive
      amination procedure. All of the above conjugates, when injected in rabbits,
      induced anti-Pn14PS antibodies, whereas the native Pn14PS did not. The amounts of
      anti-Pn14PS antibodies elicited by these conjugates, as determined by enzyme
      linked immunosorbent assay, followed a trend with conjugates containing the
      highest-molecular-weight Pn14PS eliciting the highest titers. The same trend was
      also observed in the ability of the antibodies to opsonize and kill live type 14
      pneumococci, although the increase in opsonophagocytic activity was more
      pronounced and did not correlate linearly with increases in antibody titer.
      Competitive inhibition of the binding of different conjugate antisera to the
      native Pn14PS, using Pn14PS fragments as inhibitors, established that the
      conjugates induced antibodies with specificities for different lengths of Pn14PS
      beginning at 2 repeating units (RU). It was also established, both
      immunologically and antigenically, that at least 4 RU of Pn14PS were required to
      form an extended conformational epitope and that approximately 22 RU of Pn14PS
      were required to duplicate the same epitope on the same saccharide chain. The
      conformational epitope was found to be essential for the induction of antibodies
      with high opsonophagocytic activity and that augmentation of opsonophagocytic
      activity was also dependent on further chain extension.

PMID- 9596701
TI  - Lipopolysaccharide-related stimuli induce expression of the secretory leukocyte
      protease inhibitor, a macrophage-derived lipopolysaccharide inhibitor.
AB  - Mouse secretory leukocyte protease inhibitor (SLPI) was recently characterized as
      a lipopolysaccharide (LPS)-induced product of macrophages that antagonizes their
      LPS-induced activation of NF-kappaB and production of NO and tumor necrosis
      factor (TNF) (F. Y. Jin, C. Nathan, D. Radzioch, and A. Ding, Cell 88:417-426,
      1997). To better understand the role of SLPI in innate immune and inflammatory
      responses, we examined the kinetics of SLPI expression in response to LPS, LPS
      induced cytokines, and LPS-mimetic compounds. SLPI mRNA was detectable in
      macrophages by Northern blot analysis within 30 min of exposure to LPS but levels
      peaked only at 24 to 36 h and remained elevated at 72 h. Despite the slowly
      mounting and prolonged response, early expression of SLPI mRNA was cycloheximide
      resistant. Two LPS-induced proteins-interleukin-10 (IL-10) and IL-6-also induced
      SLPI, while TNF and IL-1beta did not. The slow attainment of maximal induction of
      SLPI by LPS in vitro was mimicked by infection with Pseudomonas aeruginosa in
      vivo, where SLPI expression in the lung peaked at 3 days. Two LPS-mimetic
      molecules-taxol from yew bark and lipoteichoic acid (LTA) from gram-positive
      bacterial cell walls-also induced SLPI. Transfection of macrophages with SLPI
      inhibited their LTA-induced NO production. An anti-inflammatory role for
      macrophage-derived SLPI seems likely based on SLPI's slowly mounting production
      in response to constituents of gram-negative and gram-positive bacteria, its
      induction both as a direct response to LPS and as a response to anti-inflammatory
      cytokines induced by LPS, and its ability to suppress the production of
      proinflammatory products by macrophages stimulated with constituents of both gram
      positive and gram-negative bacteria.

PMID- 9596702
TI  - Age-dependent Neisseria meningitidis serogroup C class-specific antibody
      concentrations and bactericidal titers in sera from young children from Montana
      immunized with a licensed polysaccharide vaccine.
AB  - Neisseria meningitidis serogroup C bactericidal titers and class-specific enzyme
      linked immunosorbent assay (ELISA) antibody concentrations were measured in sera
      from 173 children (1 to 5 years old) before and 6 weeks and 7 months following
      vaccination with a quadrivalent (A/C/Y/W-135) polysaccharide vaccine. The immune
      responses of the children were compared with those of 40 adults 6 weeks
      postvaccination. Both bactericidal titers and ELISA antibody concentrations were
      significantly higher in the adults than in the children (P < 0.05). In addition,
      the ratio of immunoglobulin G (IgG) to IgM was higher in the children than in the
      adults. With an ELISA total antibody concentration of >/=2 microg/ml used as a
      measure of seroconversion, >/=84% of the individuals from each age group
      responded to the serogroup C polysaccharide. However, with a >/=4-fold-increase
      in bactericidal titer used, only 18% of 1-year-olds, 32% of 2-year-olds, and 50
      to 60% of 3-, 4-, and 5-year-olds seroconverted. The ELISA results suggest that
      >50% of all children retained >/=2 microg of total antibody per ml at 7 months
      postimmunization. However, the bactericidal titers suggest that <10% of children
      <4 years old retained a >/=4-fold increase at 7 months following vaccination. Of
      particular note, 59 of 79 sera (75%) from the 1- and 2-year-olds had high ELISA
      antibody concentrations (2 to 20 microg/ml) with no associated bactericidal titer
      (<1:8). Discordant results between bactericidal titers and ELISA antibody
      concentrations were not explained by the presence of IgA blocking antibody or
      relative levels of IgG and IgM. The bactericidal results show age-dependent
      differences in the production and retention of antibody in young children
      immunized with serogroup C polysaccharide; these differences are not evident with
      the ELISA data.

PMID- 9596703
TI  - Stable transfection of Trypanosoma cruzi epimastigotes with the trypomastigote
      specific complement regulatory protein cDNA confers complement resistance.
AB  - Trypanosoma cruzi blood stage trypomastigotes are highly resistant to complement
      mediated killing in normal serum. A previously described trypomastigote surface
      glycoprotein was shown to have binding affinity for human complement components
      C3b and C4b and restrict activation of the complement cascade, thus preventing
      lysis of the parasites. Insect stage epimastigotes do not produce detectable
      levels of this 160-kDa complement regulatory protein (CRP) and are highly
      sensitive to the lytic effects of complement. Epimastigotes were stably
      transfected with a T. cruzi expression vector carrying the trypomastigote CRP
      cDNA and produced fully functional recombinant CRP. The recombinant CRP had
      binding affinity for C3b, and the transfected epimastigotes were protected from
      complement-mediated lysis. These results demonstrate for the first time that a
      developmentally regulated gene of T. cruzi trypomastigotes can be expressed in
      noninfectious epimastigotes and that production of CRP by epimastigotes is
      sufficient to confer a virulence-associated trait. Furthermore, these studies
      demonstrate the critical role that trypomastigote CRP plays in the protection of
      parasites from the deleterious effects of complement, thus establishing the
      protein as a virulence factor of T. cruzi.

PMID- 9596704
TI  - Treatment of mice with staphylococcal enterotoxin B enhances resolution of an
      induced Escherichia coli urinary tract infection and stimulates production of
      proinflammatory cytokines.
AB  - Staphylococcal enterotoxin B (SEB) is a superantigen that causes mass
      proliferation of murine Vbeta8+ T cells via major histocompatibility complex
      (MHC) class II molecules and leads to their apoptosis or anergy. SEB also
      stimulates other MHC class II-bearing cells to proliferate and secrete cytokines,
      some of which might enhance early host defenses against urinary tract infections
      (UTIs). We investigated the effect of SEB administration on the course of an
      induced Escherichia coli UTI in mice. Treatment with SEB 3 or 7 days before the
      infection had no effect on UTI resolution. However, when SEB was administered at
      the time of infection, bacterial colonization in the bladders was reduced at time
      points between 6 h and 3 days. This reduction was not due to a physiological
      effect, such as increased urinary glycosaminoglycans, or altered pH, nor was SEB
      bactericidal for the inoculum. Cytokine production in the spleens and bladders of
      SEB-treated and/or infected mice was evaluated by reverse transcription-PCR. SEB
      treatment resulted in increased levels of interleukin-2 (IL-2), IL-4, IL-6, and
      IL-10 mRNAs in the spleen and IL-1alpha, IL-6, granulocyte-macrophage colony
      stimulating factor, and tumor necrosis factor alpha transcripts in the bladder.
      Also, liver cells from SEB-treated mice expressed IL-6 mRNA, which induces the
      production of acute-phase proteins. These data indicate that SEB treatment in
      vivo leads to enhanced UTI resolution through a mechanism that may include direct
      stimulation of effector cells in the bladder, the action of cytokines induced in
      the spleen, or cytokine-mediated induction of acute-phase proteins.

PMID- 9596706
TI  - Activity of protegrins against yeast-phase Candida albicans.
AB  - We used a two-stage radial diffusion assay to perform a structure-activity study
      of the antifungal effects of protegrin-1 (PG-1) on yeast-phase Candida albicans.
      While doing so, we computed MICs from the radial diffusion assay data by three
      methods and compared the respective values with results from colony count and
      broth microdilution assays. This allowed us to identify several technical
      modifications that improved the sensitivity and accuracy of radial diffusion
      assays. We found that both PG-1 and enantiomeric PG-1 (composed exclusively of D
      amino acids) were potently fungicidal for yeast-phase C. albicans. The protegrins
      PG-2, -3, and -5, but not PG-4, were as effective as PG-1. At least one
      intramolecular disulfide bond was required to retain optimal candidacidal
      activity at physiological NaCl concentrations. Truncated variants of PG-1 that
      lacked its first four residues showed decreased candidacidal activity, although
      their activity against bacteria was substantially intact. Altering the beta-turn
      region (residues 9 to 12) of PG-1 or its variants further decreased candidacidal
      activity. These studies suggest that only 12 residues are needed to endow
      protegrin molecules with strong antibacterial activity and that at least 4
      additional residues are needed to add potent antifungal properties. Thus, the 16
      residue protegrin PG-2 likely represents the minimal structure needed for broad
      spectrum antimicrobial activity encompassing bacteria and fungi.

PMID- 9596705
TI  - Analysis of host cells associated with the Spv-mediated increased intracellular
      growth rate of Salmonella typhimurium in mice.
AB  - The 90-kb virulence plasmid of Salmonella typhimurium encodes five spv genes
      which increase the growth rate of the bacteria within host cells within the first
      week of systemic infection of mice (P. A. Gulig and T. J. Doyle, Infect. Immun.
      61:504-511, 1993). The presently described study was aimed at identifying the
      host cells associated with Spv-mediated virulence by manipulating the mouse host
      and the salmonellae. To test the effects of T cells and B cells on the Spv
      phenotype, salmonellae were orally inoculated into nude and SCID BALB/c mice.
      Relative to normal BALB/c mice, nude and SCID BALB/c mice were unaffected for
      splenic infection with either the Spv+ or Spv- S. typhimurium strains at 5 days
      postinoculation. When mice were pretreated with cyclophosphamide to induce
      granulocytopenia, there was a variable increase in total salmonella infection,
      but the relative splenic CFU of Spv+ versus Spv- S. typhimurium was not changed
      after oral inoculation. In contrast, depletion of macrophages from mice by
      treatment with cyclophosphamide plus liposomes containing dichloromethylene
      diphosphate resulted in equivalent virulence of Spv+ and Spv- salmonellae. To
      examine if the spv genes affected the growth of salmonellae in nonphagocytic
      cells, an invA::aphT mutation was transduced into Spv+ and Spv- S. typhimurium
      strains. InvA- Spv+ salmonellae were not significantly affected for splenic
      infection after subcutaneous inoculation compared with the wild-type strain, and
      InvA- Spv- salmonellae were only slightly attenuated relative to InvA+ Spv-
      salmonellae. Invasion-defective salmonellae still exhibited the Spv phenotype.
      Therefore, infection of nonphagocytes is not involved with the Spv virulence
      function. Taken together, these data demonstrate that macrophages are essential
      for suppressing the infection by Spv- S. typhimurium, by serving as the primary
      host cell for Spv-mediated intracellular replication and possibly by inhibiting
      the replication of salmonellae within other macrophages.

PMID- 9596707
TI  - Escherichia coli cytotoxic necrotizing factor 1 effaces microvilli and decreases
      transmigration of polymorphonuclear leukocytes in intestinal T84 epithelial cell
      monolayers.
AB  - Cytotoxic necrotizing factor type 1 (CNF1), a 110-kDa toxin-like protein from
      pathogenic Escherichia coli strains, induces an actin cytoskeleton reorganization
      consisting of the formation of prominent stress fibers by permanent activation of
      the small GTP-binding protein Rho. Since p21Rho regulates tight-junction
      permeability and perijunctional actin reorganization in epithelial intestinal
      cells (A. Nusrat, M. Giry, J. R. Turner, S. P. Colgan, C. A. Parkos, E. Lemichez,
      P. Boquet, and J. L. Madara, Proc. Natl. Acad. Sci. USA 92:10629-10633, 1995), we
      used polarized T84 epithelial intestinal cell monolayers to examine whether CNF1
      could affect microvillus structure, transepithelial resistance, and
      polymorphonuclear leukocyte (PMN) transmigration. Incubation of T84 cells with
      CNF1 did not influence transepithelial resistance, suggesting that barrier
      function and surface polarity were not affected by the toxin. However, CNF1
      effaced intestinal cell microvilli and induced a strong decrease of PMN
      transepithelial migration in either the luminal-to-basolateral or the basolateral
      to-luminal direction. CNF1 could thus be a virulence factor exhibiting a new type
      of combined activity consisting of effacing of microvilli and occlusion of the
      epithelial barrier to PMNs. Attenuated transepithelial migration of PMNs could
      result in the enhanced growth and protection of luminal bacteria.

PMID- 9596709
TI  - Identification of persistent infection in experimental syphilis by PCR.
AB  - The studies described herein were designed to evaluate the usefulness of the PCR
      in detecting persistent syphilitic infection. Three groups of animals were used:
      a nonimmune group infected with Treponema pallidum (NI/TP), a nonimmune group
      injected with heat-killed treponemes (NI/HKTP), and an immune and reinfected
      group (I/TP). All animals were inoculated with similar numbers of organisms
      distributed at 10 sites on the clipped back and in both testes. The persistence
      of the treponemes was examined by PCR and the rabbit infectivity test (RIT). The
      kinetic studies and statistical analysis of their results demonstrated that the
      rate of bacterial clearance from the NI/TP group was very low and incomplete at 4
      months after infection. It was significantly different from those of both the
      NI/HKTP (P < 0.001) and I/TP (P < 0.05) groups. No statistically significant
      differences in treponemal elimination were found between the NI/HKTP and I/TP
      groups. PCR can detect the DNA of dead organisms, but the latter are eliminated
      by the host relatively quickly (15 to 30 days) as compared to elimination of live
      treponemes (>120 days). PCR results correlated well with RIT results. These data
      suggest that PCR-positive specimens obtained from an untreated patient(s) or
      collected weeks after treatment indicate persistent infection. They also show
      that the process of elimination of T. pallidum from primary sites of infection is
      prolonged and incomplete.

PMID- 9596708
TI  - Neurotoxicity of Clostridium perfringens epsilon-toxin for the rat hippocampus
      via the glutamatergic system.
AB  - The neurotoxicity of epsilon-toxin, one of the major lethal toxins produced by
      Clostridium perfringens type B, was studied by histological examination of the
      rat brain. When the toxin was injected intravenously at a lethal dose (100
      ng/kg), neuronal damage was observed in many areas of the brain. Injection of the
      toxin at a sublethal dose (50 ng/kg) caused neuronal damage predominantly in the
      hippocampus: pyramidal cells in the hippocampus showed marked shrinkage and
      karyopyknosis, or so-called dark cells. The dark cells lost the immunoreactivity
      to microtubule-associated protein-2, a postsynaptic somal and dendric marker,
      while acetylcholinesterase-positive fibers were not affected. Timm's zinc
      staining revealed that zinc ions were depleted in the mossy layers of the CA3
      subfield containing glutamate as a synaptic transmitter. The cerebral blood flow
      in the hippocampus was not altered significantly before or after administration
      of the toxin, as measured by laser-Doppler flowmetry, excluding the possibility
      that the observed histological change was due to a secondary effect of ischemia
      in the hippocampus. Prior injection of either a glutamate release inhibitor or a
      glutamate receptor antagonist protected the hippocampus from the neuronal damage
      caused by epsilon-toxin. These results suggest that epsilon-toxin acts on the
      glutamatergic system and evokes excessive release of glutamate, leading to
      neuronal damage.

PMID- 9596710
TI  - Protein kinase A-mediated inhibition of gamma interferon-induced tyrosine
      phosphorylation of Janus kinases and latent cytoplasmic transcription factors in
      human monocytes by Ehrlichia chaffeensis.
AB  - Ehrlichia chaffeensis, an obligatory intracellular bacterium of monocytes or
      macrophages, is the etiologic agent of human monocytic ehrlichiosis. Our previous
      study showed that gamma interferon (IFN-gamma) added prior to or at early stage
      of infection inhibited infection of human monocytes with E. chaffeensis; however,
      after 24 h of infection, IFN-gamma had no antiehrlichial effect. To test whether
      ehrlichial infection disrupts Janus kinase (Jak) and signal transducer and
      activator of transcription (Stat) signaling induced by IFN-gamma, tyrosine
      phosphorylation of Stat1, Jak1, and Jak2 in E. chaffeensis-infected THP-1 cells
      was examined by immunoprecipitation followed by immunoblot analysis. Viable E.
      chaffeensis organisms blocked tyrosine phosphorylation of Stat1, Jak1, and Jak2
      in response to IFN-gamma within 30 min of infection. Similar results were
      obtained with human peripheral blood monocytes infected with E. chaffeensis. Heat
      or proteinase K treatment but not periodate treatment of E. chaffeensis abrogated
      the inhibitory effect, suggesting that protein factor(s) of E. chaffeensis is
      responsible for the inhibition of IFN-gamma-induced tyrosine phosphorylation.
      Preincubation of E. chaffeensis with the Fab fragment of dog anti-E. chaffeensis
      immunoglobulin G also abrogated the inhibitory effect. On the other hand,
      monodansylcadaverine, which does not block binding but blocks internalization of
      ehrlichiae into macrophages, did not have any influence on the tyrosine
      phosphorylation. These results indicate that ehrlichial binding to host cells is
      sufficient to inhibit Stat1 tyrosine phosphorylation induced by IFN-gamma.
      Protein kinase A (PKA) activity in THP-1 cells increased approximately 25-fold
      within 30 min of infection with E. chaffeensis. In THP-1 cells pretreated with a
      PKA inhibitor, Rp isomer of adenosine 3',5'-cyclic phosphorothioate, E.
      chaffeensis-induced inhibition of Stat1 tyrosine phosphorylation was partially
      abrogated. These results suggest that E. chaffeensis blocks IFN-gamma-induced
      tyrosine phosphorylation of Jak and Stat through raising PKA activity in THP-1
      cells, which may be an important survival mechanism of ehrlichiae within the host
      cell.

PMID- 9596711
TI  - Pseudomonas aeruginosa lasR transcription correlates with the transcription of
      lasA, lasB, and toxA in chronic lung infections associated with cystic fibrosis.
AB  - The role of Pseudomonas aeruginosa quorum-sensing systems in the lung infections
      associated with cystic fibrosis (CF) has not been examined. The purpose of this
      study was to determine if genes regulated by the LasR-LasI quorum-sensing system
      were coordinately regulated by the P. aeruginosa populations during the lung
      infections associated with CF. We also wanted to ascertain if there was a
      relationship between the expression of lasR, a transcriptional regulator, and
      some P. aeruginosa virulence factors during these infections. We extracted RNAs
      from the bacterial populations of 131 sputa taken from 23 CF patients. These RNAs
      were blotted and hybridized with probes to P. aeruginosa lasA, lasB, and toxA.
      The hybridization signals from each probe were ranked, and the rankings were
      analyzed by a Spearman rank correlation to determine if there was an association
      between the population transcript accumulations for the three genes. The
      correlations between the transcript accumulation patterns of pairs of the genes
      suggested that lasA, lasB, and toxA might be coordinately regulated during CF
      lung infections. To determine if this coordinate regulation might be due to
      regulation by LasR, we probed RNAs, extracted from 84 sputa, with the lasR, lasA,
      lasB, toxA, and algD probes. Statistical analysis indicated that lasR transcript
      accumulation correlated to lasA, lasB, toxA, and algD transcript accumulations.
      These results indicated that lasR may at least partially regulate or be
      coordinately regulated with lasA, lasB, toxA, and algD during the lung infections
      associated with CF. These results also suggested that the LasR-LasI quorum
      sensing system may control the expression of at least some virulence factors in
      the lungs of patients with CF.

PMID- 9596712
TI  - In vitro expression of adhesion receptors and diapedesis by polymorphonuclear
      neutrophils during experimentally induced Streptococcus uberis mastitis.
AB  - The expression of adhesion receptors and diapedesis by polymorphonuclear
      neutrophils (PMN) were studied before and during experimentally induced
      Streptococcus uberis mastitis. Both quarters of the left half of the udders of
      five midlactation cows were inoculated with a suspension containing approximately
      500 CFU of S. uberis 0140J. Clinical signs of an inflammatory reaction and
      leukocyte influx were observed 24 h after challenge. The expression of CD11b/CD18
      adhesion receptors, determined by flow cytometry, was upregulated 24 h after
      challenge. A confluent monolayer of bovine secretory mammary epithelial cells on
      collagen-coated inserts was used to study PMN diapedesis. Bovine C5a was used as
      the chemoattractant. An 80% decrease in PMN diapedesis was observed 24 h after
      challenge. The decrease in diapedesis continued for 3 weeks after challenge.

PMID- 9596713
TI  - The Vibrio cholerae mannose-sensitive hemagglutinin is the receptor for a
      filamentous bacteriophage from V. cholerae O139.
AB  - We previously isolated from a 1994 isolate of Vibrio cholerae O139 a filamentous
      lysogenic bacteriophage, choleraphage 493, which inhibits pre-O139 but not post
      O139 El Tor biotype V. cholerae strains in plaque assays. We investigated the
      role of the mannose-sensitive hemagglutinin (MSHA) type IV pilus as a receptor in
      phage 493 infection. Spontaneous, Tn5 insertion, and mshA deletion mutants are
      resistant to 493 infection. Susceptibility is restored by mshA complementation of
      deletion mutants. Additionally, the 493 phage titer is reduced by adsorption with
      MSHA-positive strains but not with a DeltamshA1 strain. Monoclonal antibody
      against MSHA inhibits plaque formation. We conclude that MSHA is the receptor for
      phage 493. The emergence and decline of O139 in India and Bangladesh are
      correlated with the susceptibility and resistance of El Tor strains to 493.
      However, mshA gene sequences of post-O139 strains are identical to those of
      susceptible pre-O139 isolates, indicating that phage resistance of El Tor is not
      due to a change in mshA. Classical biotype strains are (with rare exceptions)
      hemagglutinin negative and resistant to 493 in plaque assays. Nevertheless, they
      express the mshA pilin gene. They can be infected with 493 and produce low levels
      of phage DNA, like post-O139 El Tor strains. Resistance to 493 in plaque assays
      is thus not equivalent to resistance to infection. The ability of filamentous
      phages, such as 493, to transfer large amounts of DNA provides them,
      additionally, with the potential for quantum leaps in both identity and
      pathogenicity, such as the conversion of El Tor to O139.

PMID- 9596714
TI  - Borrelia burgdorferi escape mutants that survive in the presence of antiserum to
      the OspA vaccine are killed when complement is also present.
AB  - As an initial attempt to investigate the possible role of outer surface protein A
      (OspA) escape mutants of Borrelia burgdorferi in decreasing the efficacy of the
      OspA vaccine, mutants of the HB19 strain of B. burgdorferi sensu stricto were
      selected in vitro from an uncloned, low-passage-number isolate. The antiserum
      used for selection was obtained from rhesus monkeys that had been given a vaccine
      of the same formulation and dose, and by the same route of administration, as
      that given to humans in several trials. All of the mutants selected in liquid
      medium and subsequently cloned twice in solid medium expressed a single abundant
      protein of 28 to 34 kDa instead of both OspA and OspB. Depending on the mutant,
      this protein reacted strongly, weakly, or not detectably with the anti-OspA
      antibody used for selection. Analysis of the ospAB locus of each of four
      representatives from these three groups of mutants by PCR with oligonucleotide
      primers that hybridize to flanking regions of the ospAB operon, and of the
      corresponding phenotype with monoclonal antibodies that bind to the amino or
      carboxyl terminus of the OspA or OspB polypeptide, indicated that in all cases a
      deletion within the operon had occurred. Spirochetes from the four mutant strains
      chosen for further analysis could be killed in antibody-dependent, complement
      mediated killing assays with the selecting anti-OspA antibody, despite their
      resistance to killing with this antibody in the absence of complement. Complement
      mediated killing occurred at an antibody concentration higher than that required
      to kill wild-type spirochetes. If anti-OspA antibody acts only within the tick,
      where complement is probably ineffective due to tick-derived decomplementing
      factors, then OspA escape mutants, if infectious, could seriously diminish the
      efficacy of OspA vaccines. On the other hand, if the killing of B. burgdorferi
      with anti-OspA antibody also takes place within the human host, then our results
      indicate that chimeric/deletion escape mutants will be killed as well.

PMID- 9596715
TI  - Mitogenic response of murine B lymphocytes to Salmonella typhimurium
      lipopolysaccharide requires protein kinase C-dependent late tyrosine
      phosphorylations.
AB  - Unlike the cross-linking of membrane immunoglobulins, the activation of B cells
      by lipopolysaccharide (LPS) does not involve the phosphoinositol turnover and the
      initial activation of tyrosine kinases. However, LPS-induced B-cell proliferation
      was inhibited by the tyrosine kinase inhibitors genistein and herbimycin A even
      when added 48 h after the beginning of the culture. Tyrosyl-phosphorylated
      proteins were detected by Western blotting after 24 h of culture with LPS,
      reaching a maximum concentration after 72 h. Late tyrosine phosphorylations were
      also detected in B cells activated for 72 h with anti-immunoglobulin M antibody
      and were abrogated by the protein synthesis inhibitor cycloheximide, the tyrosine
      kinase inhibitors genistein and herbimycin A, and the protein kinase C inhibitor
      chelerythrine. The role of protein kinase C in late tyrosine kinase activation is
      independent of Ca2+ mobilization and was confirmed by detection of a comparable
      but restricted pattern of tyrosine-phosphorylated substrates in B cells treated
      with phorbol myristate acetate alone or in association with ionomycin. Tyrosine
      kinase activation was dependent on de novo protein synthesis. However, culture
      supernatants of LPS-activated B cells were devoid of mitogenic activity and
      induced a phosphorylation pattern more restricted than that achieved by LPS.
      Altogether these data indicate that proliferation signals induced by LPS or by
      the cross-linking of membrane immunoglobulins are controlled by late tyrosine
      phosphorylations occurring throughout the first 3 days of culture, controlled in
      part by protein kinase C activation, and dependent on the synthesis of an
      intermediate protein(s) either not secreted in the culture supernatant or present
      but biologically inactive in naive B cells.

PMID- 9596716
TI  - Evolution of enterohemorrhagic Escherichia coli hemolysin plasmids and the locus
      for enterocyte effacement in shiga toxin-producing E. coli.
AB  - This study assessed the diversity of the enterohemorrhagic Escherichia coli
      (EHEC) hemolysin gene (ehxA) in a variety of Shiga toxin-producing E. coli (STEC)
      serotypes and the relationship between ehxA types and virulence markers on the
      locus for enterocyte effacement (LEE). Restriction fragment length polymorphism
      of the ehxA gene and flanking sequences and of the E. coli attaching and effacing
      (eae) gene was determined for 79 EHEC hemolysin-positive STEC isolates of 37
      serotypes. Two main groups of EHEC hemolysin sequences and associated plasmids,
      which corresponded to the eae-positive and the eae-negative isolates, were
      delineated. Comparisons of the ehxA gene sequences of representative isolates of
      each group showed that this gene and the rest of the EHEC hemolysin operon are
      highly conserved. Digestion of an ehxA PCR product with the restriction
      endonuclease TaqI showed a unique restriction pattern for eae-negative isolates
      and another one for isolates of serotypes O157:H7 and O157:NM. A conserved
      fragment of 5.6 kb with four potential open reading frames was identified on the
      EHEC hemolysin plasmid of eae-positive STEC. Phylogenetic analysis of a subset of
      27 STEC isolates, one enteropathogenic E. coli isolate, and a K-12 reference
      isolate showed that eae-positive STEC isolates all belong to a single
      evolutionary lineage and that the EHEC hemolysin plasmid and the ehxA gene
      evolved within this lineage without recent horizontal transfer. However, the eae
      gene and the LEE appear to have been transferred horizontally within this STEC
      lineage on several occasions. The reasons for the lack of transfer or maintenance
      of the LEE in other STEC lineages are not clear and require further study.

PMID- 9596717
TI  - Lipopolysaccharide and its analog antagonists display differential serum factor
      dependencies for induction of cytokine genes in murine macrophages.
AB  - Monocytes/macrophages play a central role in mediating the effects of
      lipopolysaccharide (LPS) derived from gram-negative bacteria by the production of
      proinflammatory mediators. Recently, it was shown that the expression of cytokine
      genes for tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      and interferon-inducible protein-10 (IP-10) by murine macrophages in response to
      low concentrations of LPS is entirely CD14 dependent. In this report, we show
      that murine macrophages respond to low concentrations of LPS (</=2 ng/ml) in the
      complete absence of serum, leading to the induction of TNF-alpha and IL-1beta
      genes. In contrast to the TNF-alpha and IL-1beta genes, the IP-10 gene is poorly
      induced in the absence of serum. The addition of recombinant human soluble CD14
      (rsCD14) had very little effect on the levels of serum-free, LPS-induced TNF
      alpha, IL-1beta, and IP-10 genes. In contrast, the addition of recombinant human
      LPS-binding protein (rLBP) had opposing effects on the LPS-induced TNF-alpha or
      IL-1beta and IP-10 genes. rLBP inhibited LPS-induced TNF-alpha and IL-1beta
      genes, while it reconstituted IP-10 gene expression to levels induced in the
      presence of serum. These results provide further evidence that the induction of
      TNF-alpha or IL-1beta genes occurs via a pathway that is distinct from one that
      leads to the induction of the IP-10 gene and that the pathways diverge at the
      level of the initial interaction between LPS and cellular CD14. Additionally, the
      results presented here indicate that LPS structural analog antagonists
      Rhodobacter sphaeroides diphosphoryl lipid A and SDZ 880. 431 are able to inhibit
      LPS-induced TNF-alpha and IL-1beta in the absence of serum, while a synthetic
      analog of Rhodobacter capsulatus lipid A (B 975) requires both rsCD14 and rLBP to
      function as an inhibitor.

PMID- 9596718
TI  - Disparate findings on the role of virulence factors of Enterococcus faecalis in
      mouse and rat models of peritonitis.
AB  - The role of Enterococcus faecalis in polymicrobial peritonitis is still debated.
      Virulence factors expressed in some enterococcal strains might be involved in the
      pathogenicity of these organisms. To clarify their role, three of these virulence
      factors (cytolysin, gelatinase, and aggregation substance) were studied in six
      isogenic strains of E. faecalis expressing various combinations of these factors.
      Since the pathogenic effects of enterococci are only moderate, the expression of
      their virulence might vary from one animal species to another and from one type
      of infection to another. Therefore, we evaluated these effects in two animal
      models, i.e., a systemic infection in mice in which we assessed the virulence of
      the strains in 50% lethal dose studies and a model of compartmentalized infection
      in rats in which the microbiologic and inflammatory effects of the strains were
      evaluated in monomicrobial or polymicrobial infection. In mice, significant
      differences were observed in the cumulative survival curves depending on the
      virulence factors (P < 0.0001 [log rank test]). In rats, monomicrobial infection
      induced only mild changes. In polymicrobial peritonitis, the virulence factors
      mainly increased the inflammatory response while the changes observed in the
      microbiologic response were minimal. The combination of two virulence factors did
      not significantly increase the severity of infection either in the mice model or
      the polymicrobial rat model. These data argue for species and model dependence of
      the role of the virulence factors studied here and suggest that other important
      factors may be involved in the pathogenicity of enterococci.

PMID- 9596719
TI  - Molecular characterization of Mycoplasma arthritidis variable surface protein
      MAA2.
AB  - Earlier studies implied a role for Mycoplasma arthritidis surface protein MAA2 in
      cytadherence and virulence and showed that it exhibited both size and phase
      variability. Here we report the further analysis of MAA2 and the cloning and
      sequencing of the maa2 gene from two M. arthritidis strains, 158p10p9 and H606,
      expressing two size variants of MAA2. Triton X-114 partitioning and metabolic
      labeling with [3H]palmitic acid suggested lipid modification of MAA2. Surface
      exposure of the C terminus was indicated by cleavage of monoclonal antibody
      specific epitopes from intact cells by carboxypeptidase Y. The maa2 genes from
      both strains were highly conserved, consisting largely of six (for 158p10p9) or
      five (for H606) nearly identical, 264-bp tandem direct repeats. The deduced amino
      acid sequence predicted a largely hydrophilic, highly basic protein with a 29
      amino-acid lipoprotein signal peptide. The maa2 gene was expressed in Escherichia
      coli from the lacZ promoter of vector pGEM-T. The recombinant product was
      approximately 3 kDa larger than the native protein, suggesting that the signal
      peptide was not processed in E. coli. The maa2 gene and upstream DNA sequences
      were cloned from M. arthritidis clonal variants differing in MAA2 expression
      state. Expression state correlated with the length of a poly(T) tract just
      upstream of a putative -10 box. Full-sized recombinant MAA2 was expressed in E.
      coli from genes derived from both ON and OFF expression variants, indicating that
      control of expression did not include alterations within the coding region.

PMID- 9596720
TI  - Volatile fatty acid, metabolic by-product of periodontopathic bacteria, induces
      apoptosis in WEHI 231 and RAJI B lymphoma cells and splenic B cells.
AB  - The ability of butyric acid, an extracellular metabolite from periodontopathic
      bacteria, to induce apoptosis in murine WEHI 231 cells, splenic B cells, and
      human RAJI cells was examined. The culture filtrate of Porphyromonas gingivalis,
      Prevotella loescheii, and Fusobacterium nucleatum, which contains high a
      percentage of butyric acid, induced DNA fragmentation in WEHI 231 cells. Volatile
      fatty acid, especially butyric acid, significantly suppressed B-cell viability in
      a concentration-dependent fashion. The DNA fragmentation assay indicated that
      butyric acid rapidly induced apoptosis in WEHI 231 cells (with 1.25 mM butyric
      acid and 6 h after treatment), splenic B cells (with 1.25 mM butyric acid), and
      RAJI cells (with 2.5 mM butyric acid). Incubation of WEHI 231 cells with butyric
      acid for 16 h resulted in the typical ladder pattern of DNA fragmentation and the
      apoptoic change such as chromatin condensation and hypodiploid nuclei. Cell cycle
      analysis implied that butyric acid arrested the cells at the G1 phase. The
      inhibitory assay suggested that butyric acid-induced apoptosis of WEHI 231 and
      splenic B cells was inhibited by W-7, a calmodulin inhibitor. These results
      suggest that calmodulin-dependent regulation is involved in the signal
      transduction pathway of butyric acid.

PMID- 9596721
TI  - Mutacin production by Streptococcus mutans may promote transmission of bacteria
      from mother to child.
AB  - The production of bacteriocin-like inhibitory substances, mutacins, by mutans
      streptococci varies among isolates. To find if the degree of mutacin activity of
      an isolate was related to its transmission between mother and her child, 19
      mothers and their 18-month- to 3-year-old children were sampled for their oral
      mutans streptococci. In addition, the stability of mutacin activity was studied
      with isolates from the mothers and with isolates from five unrelated 5-year-old
      children in 5- to 7-year follow-up studies. A total of 145 oral mutans
      streptococcal isolates were serotyped by immunodiffusion, ribotyped, and mutacin
      typed by the stab culture technique. Mutacin was produced by 88% of the strains
      against more than 1 of the 14 indicator strains, representing mutans
      streptococci, Streptococcus sanguis, Streptococcus salivarius, Streptococcus
      oralis, Streptococcus gordonii, and Streptococcus pyogenes. Streptococcus mutans
      isolates showed more inhibitory activity than did Streptococcus sobrinus
      isolates. Identical ribotypes had similar mutacin activity profiles within a
      subject, initially and in the follow-up studies, in all but two cases. The
      mothers harbored a total of 37 different mutans streptococcal ribotypes. Six
      children were negative for mutans streptococci. Transmission was probable in 9 of
      20 mother-child pairs on the basis of the presence of identical strains, as
      determined by ribotyping and bacteriocin (mutacin) typing. S. mutans strains
      shared between a mother and her child showed a broader spectrum of inhibitory
      activity than did nontransmitted strains. In conclusion, the mutacin activity of
      clinical isolates is reasonably stable, and this virulence factor seems to be of
      clinical importance in early colonization by S. mutans.

PMID- 9596722
TI  - An epimerase gene essential for capsule synthesis in Vibrio vulnificus.
AB  - The extracellular capsule polysaccharide (CPS) of Vibrio vulnificus is a primary
      virulence factor which allows survival of the bacteria in the human host. To
      study the genes involved in expression of the capsule, we generated mutants that
      lost the ability to produce CPS following the insertion of a minitransposon into
      the genome of an encapsulated, clinical strain of V. vulnificus. A genomic
      region, from one nonencapsulated mutant, containing the transposon and flanking
      V. vulnificus DNA was cloned, and a probe complementary to the chromosomal DNA
      immediately adjacent to the transposon was used to locate this fragment in the
      genome of the encapsulated parent strain. The fragment, which contained a
      putative capsule gene, was cloned and, when supplied in trans, complemented the
      mutation in the nonencapsulated mutant to restore capsule production. In
      addition, virulence studies, using the 50% lethal dose assay, showed that the
      restoration of capsule production also restored the virulence of the organism.
      Sequence analysis of the gene disrupted by the transposon revealed that it
      matched a nucleotide-sugar epimerase of Vibrio cholerae O139, with 75 and 85%
      identities at the nucleotide and amino acid levels, respectively. In addition,
      computer analysis recognized epimerases of various organisms as highly similar to
      the putative epimerase of V. vulnificus. Finally, a combination of PCR
      amplification and Southern blotting showed that this epimerase is common to at
      least 10 strains of V. vulnificus that each express a serologically distinct CPS.
      Our results indicate that the epimerase gene is essential for capsule expression
      in V. vulnificus.

PMID- 9596723
TI  - Modification of Ras in eukaryotic cells by Pseudomonas aeruginosa exoenzyme S.
AB  - Genetic and functional data suggest that Pseudomonas aeruginosa exoenzyme S
      (ExoS), an ADP-ribosyltransferase, is translocated into eukaryotic cells by a
      bacterial type III secretory mechanism activated by contact between bacteria and
      host cells. Although purified ExoS is not toxic to eukaryotic cells, ExoS
      producing bacteria cause reduced proliferation and viability, possibly mediated
      by bacterially translocated ExoS. To investigate the activity of translocated
      ExoS, we examined in vivo modification of Ras, a preferred in vitro substrate.
      The ExoS-producing strain P. aeruginosa 388 and an isogenic mutant strain,
      388DeltaexoS, which fails to produce ExoS, were cocultured with HT29 colon
      carcinoma cells. Ras was found to be ADP-ribosylated during coculture with 388
      but not with 388DeltaexoS, and Ras modification by 388 corresponded with
      reduction in HT29 cell DNA synthesis. Active translocation by bacteria was found
      to be required, since exogenous ExoS, alone or in the presence of 388DeltaexoS,
      was unable to modify intracellular Ras. Other ExoS-producing strains caused
      modification of Ras, indicating that this is not a strain-specific event. ADP
      ribosylation of Rap1, an additional Ras family substrate for ExoS in vitro, was
      not detectable in vivo under conditions sufficient for Ras modification,
      suggesting possible ExoS substrate preference among Ras-related proteins. These
      results confirm that intracellular Ras is modified by bacterially translocated
      ExoS and that the inhibition of target cell proliferation correlates with the
      efficiency of Ras modification.

PMID- 9596724
TI  - Experimental Helicobacter pylori infection induces antral gastritis and gastric
      mucosa-associated lymphoid tissue in guinea pigs.
AB  - Humans infected with Helicobacter pylori have abnormally low levels of the
      antioxidant vitamin C, which protects against the formation of carcinogenic
      nitrosamines, in gastric juice. Guinea pigs, like humans and nonhuman primates,
      have a dietary requirement for vitamin C. As such, these species have
      gastrointestinal vitamin C transport systems not found in other animals. We have
      developed and characterized a guinea pig model of chronic gastric H. pylori
      infection with the rodent-adapted Sydney strain of H. pylori. At 4 weeks
      postinfection, five of six animals of the infected group and zero of two animals
      of the control group were positive for H. pylori as determined by culture or PCR.
      At 15 weeks, six of six animals of the infected group and zero of two animals of
      the control group were positive. H. pylori-specific seroconversion was observed
      among infected animals. There were no histologic abnormalities in the gastric
      antra or fundi of control guinea pigs. In contrast, there was multifocal, mild to
      moderate lymphohistiocytic antral gastritis and formation of antral lymphoid
      follicles in H. pylori-infected animals. The lesion distribution in the gastric
      antra paralleled that observed in H. pylori-infected humans. The H. pylori
      infected guinea pig should prove useful in modeling the interaction of
      helicobacter and vitamin C in gastric carcinogenesis.

PMID- 9596725
TI  - Conformational dependence of Anaplasma marginale major surface protein 5 surface
      exposed B-cell epitopes.
AB  - The Anaplasma marginale outer membrane is composed of immunogenic major surface
      proteins (MSPs) linked both covalently and noncovalently in multimeric complexes
      (M. C. Vidotto, T. C. McGuire, T. F. McElwain, G. H. Palmer, and D. P. Knowles,
      Infect. Immun. 62:2940-2946). Consequently, effective induction of antibody
      against surface-exposed MSP epitopes has been postulated to require maintenance
      of MSP secondary through quatenary structures. Using MSP5 as a model and the
      approach of epitope mapping with recombinant expressed full-length and truncated
      proteins, we demonstrated that the immunodominant surface epitope bound by
      monoclonal antibody (MAb) ANAF16C1 required disparate amino- and carboxy-terminal
      regions of MSP5, indicating the conformational dependence of this epitope. The
      required amino-terminal MSP5 region included the cysteines involved in
      intramolecular disulfide bonding. The dependence of the immunodominant epitope on
      disulfide bonding was confirmed by loss of MAb ANAF16C1 binding to MSP5 following
      disulfide bond reduction and covalent modification of the reduced sulfhydryl
      groups. The recognition of the MSP5 immunodominant epitope by antibody induced by
      protective immunization with A. marginale outer membranes was also
      conformationally dependent, as shown by the loss of epitope binding following
      serum adsorption with native but not reduced and denatured A. marginale.
      Importantly, the antibody response to all immunodominant MSP5 surface epitopes
      was restricted to conformationally dependent epitopes, since the binding of
      polyclonal anti-MSP5 antibody to the A. marginale surface could be blocked by
      adsorption with native but not denatured and reduced MSP5. These results confirm
      the importance of the secondary and tertiary structures of MSP epitopes as immune
      system targets and support the testing of immunogens which maintain the required
      conformation.

PMID- 9596727
TI  - Antigen-induced protective and nonprotective cell-mediated immune components
      against Cryptococcus neoformans.
AB  - Mice immunized with two different cryptococcal antigen preparations, one a
      soluble culture filtrate antigen (CneF) in complete Freund's adjuvant (CFA) and
      the other heat-killed Cryptococcus neoformans cells (HKC), develop two different
      profiles of activated T cells. CneF-CFA induces CD4+ T cells responsible for
      delayed-type hypersensitivity (DTH) reactivity and for amplification of the
      anticryptococcal DTH response, whereas HKC induce CD4+ and CD8+ T cells involved
      in anticryptococcal DTH reactivity and activated T cells which directly kill C.
      neoformans cells. The main purpose of this study was to assess the level of
      protection afforded by each of the two different T-cell profiles against
      challenge with viable C. neoformans cells, thereby identifying which activated T
      cell profile provides better protection. CBA/J mice immunized with CneF-CFA had
      significantly better protective responses, based on better clearance of C.
      neoformans from tissues, on longer survival times, and on fewer and smaller
      lesions in the brain, than HKC-immunized mice or control mice similarly infected
      with C. neoformans. Both immunization protocols induced an anticryptococcal DTH
      response, but neither induced serum antibodies to glucuronoxylmannan, so the
      protection observed in the CneF-CFA immunized mice was due to the activated T
      cell profile induced by that protocol. HKC-immunized mice, which displayed no
      greater protection than controls, did not have the amplifier cells. Based on our
      findings, we propose that the protective anticryptococcal T cells are the CD4+ T
      cells which have been shown to be responsible for DTH reactivity and/or the CD4+
      T cells which amplify the DTH response and which have been previously shown to
      produce high levels of gamma interferon and interleukin 2. Our results imply that
      there are protective and nonprotective cell-mediated immune responses and
      highlight the complexity of the immune response to C. neoformans antigens.

PMID- 9596726
TI  - Mapping and identification of the major cell wall-associated components of
      Mycobacterium leprae.
AB  - Mycobacterium leprae, an obligate intracellular pathogen, can be derived only
      from host tissue and thus affords the opportunity to study in vivo-expressed
      products responsible for the particular pathogenesis of leprosy. Despite
      considerable progress in the characterization of the proteins and secondary gene
      products of M. leprae, there is little information on the nature of the proteins
      associated with the cell envelope. M. leprae has been fractionated into its major
      subcellular components, cell wall, cytoplasmic membrane, and soluble cytosol. A
      number of biochemical markers, including diaminopimelic acid content,
      monosaccharide composition, mycolic acid, and glycolipid distribution, were
      applied to their characterization, and two-dimensional gel electrophoresis was
      used to map the component proteins. A total of 391 major proteins spots were
      resolved, and 8 proteins were identified based on their reactivity to a panel of
      monoclonal antibodies and/or relative pI size. Microsequencing of six protein
      spots present in the cell wall fraction allowed identification of new proteins,
      including the protein elongation factor EF-Tu and a homolog for the Mycobacterium
      tuberculosis MtrA response regulator. These results, together with previous
      studies, contribute to the progressive knowledge of the composition of the in
      vivo-expressed proteins of M. leprae.

PMID- 9596728
TI  - Interleukin-15 activates proinflammatory and antimicrobial functions in
      polymorphonuclear cells.
AB  - Interleukin-15 (IL-15) is a recently discovered cytokine produced by a wide range
      of different cell types including fibroblasts, keratinocytes, endothelial cells,
      and macrophages in response to lipopolysaccharide or microbial infection. This
      suggests that IL-15 may play a crucial role in the activation of phagocytic cells
      against pathogens. We studied polymorphonuclear leukocyte (PMN) activation by IL
      15, evaluated as enhancement of PMN anti-Candida activity as well as IL-8
      production, following stimulation with the cytokine. The PMN response to IL-15
      depends on binding to the IL-15 receptor. Our experiments show that binding of a
      biotinylated human IL-15-immunoglobulin G2b IgG2b fusion protein was competed by
      the addition of human recombinant IL-15 (rIL-15) or of human rIL-2, suggesting
      that IL-15 binding to PMN might involve the IL-2Rbeta and IL-2Rgamma chains,
      which have been shown to be constitutively expressed by PMN. In addition, we show
      by reverse transcription-PCR and by flow cytometry with a specific anti-IL
      15Ralpha chain monoclonal antibody that PMN express the IL-15Ralpha chain at the
      mRNA and protein levels. Incubation with IL-15 activated PMN to secrete the
      chemotactic factor IL-8, and the amount secreted was increased by costimulation
      with heat-inactivated Candida albicans. In addition, IL-15 primed the metabolic
      burst of PMN in response to formyl-methionyl-leucyl-phenylalanine but was not
      sufficient to trigger the respiratory burst or to increase the production of
      superoxide in PMN exposed to C. albicans. IL-15 also increased the ability of PMN
      to phagocytose heat-killed C. albicans organisms in a dose-dependent manner,
      without opsonization by antibodies or complement-derived products. In the same
      concentration range, IL-15 was as effective as gamma interferon (IFN-gamma) and
      IL-2 in increasing the C. albicans growth-inhibitory activity of PMN. Taken
      together, these results suggest that IL-15 is a potent stimulant of both
      proinflammatory and antifungal activities of PMN, activating several
      antimicrobial functions of PMN involved in the cellular response against C.
      albicans.

PMID- 9596729
TI  - Borrelia burgdorferi erp proteins are immunogenic in mammals infected by tick
      bite, and their synthesis is inducible in cultured bacteria.
AB  - Borrelia burgdorferi, the causative agent of Lyme disease, can contain multiple
      genes encoding different members of the Erp lipoprotein family. Some arthropod
      borne bacteria increase the synthesis of proteins required for transmission or
      mammalian infection when cultures are shifted from cool, ambient air temperature
      to a warmer, blood temperature. We found that all of the erp genes known to be
      encoded by infectious isolate B31 were differentially expressed in culture after
      a change in temperature, with greater amounts of message being produced by
      bacteria shifted from 23 to 35 degrees C than in those maintained at 23 degrees
      C. Mice infected with B31 by tick bite produced antibodies that recognized each
      of the Erp proteins within 4 weeks of infection, suggesting that the Erp proteins
      are produced by the bacteria during the early stages of mammalian infection and
      may play roles in transmission from ticks to mammals. Several of the B31 Erp
      proteins were also recognized by antibodies from patients with Lyme disease and
      may prove to be useful antigens for diagnostic testing or as components of a
      protective vaccine.

PMID- 9596730
TI  - Differential effects of myeloperoxidase-derived oxidants on Escherichia coli DNA
      replication.
AB  - The microbicidal myeloperoxidase (MPO)-H2O2-chloride system strongly inhibits
      Escherichia coli DNA synthesis. Also, cell envelopes from MPO-treated E. coli
      cells lose their ability to interact with hemimethylated DNA sequences of oriC,
      the chromosomal origin of replication, raising the prospect that suppression of
      DNA synthesis involves impairment of oriC-related functions (H. Rosen, et al.
      Proc. Natl. Acad. Sci. USA, 87:10048-10052, 1990). To evaluate whether origin
      specific DNA sequences play a role in the MPO effect on E. coli DNA synthesis,
      plasmid DNA replication was compared to total (chromosomal) DNA replication for
      six plasmids with three distinct origins of replication. Plasmid pCM700
      replication, replicating from oriC, was as sensitive to MPO-mediated inhibition
      as was total (chromosomal) DNA replication. A regression line describing this
      relationship had a slope of 0.90, and the r2 was 0.89. In contrast, the
      replication activities of three of four non-oriC plasmids, pUC19, pACYC184, and
      pSC101, demonstrated significant early resistance to inhibition by MPO-derived
      oxidants. The exception to this resistance pattern was plasmid pSP102, which has
      an origin derived from P1 phage. pSP102 replication declined similarly to that of
      total DNA synthesis. The regression line for pSP102 replication versus total DNA
      synthesis had a slope of 0.95, and the r2 was 0.92. The biochemical requirements
      for P1-mediated replication are strikingly similar to those for oriC-mediated
      replication. It is proposed that one of these requirements, common to oriC and
      the P1 origin but not critical to the replication of the other non-oriC plasmids,
      is an important target for MPO-mediated oxidations that mediate the initial
      decline in E. coli chromosomal DNA synthesis.

PMID- 9596731
TI  - Clostridium difficile toxin B induces apoptosis in intestinal cultured cells.
AB  - Toxigenic strains of the anaerobic bacterium Clostridium difficile produce at
      least two large, single-chain protein exotoxins involved in the pathogenesis of
      antibiotic-associated diarrhea and colitis. Toxin A (CdA) is a cytotoxic
      enterotoxin, while toxin B (CdB) is a more potent cytotoxin lacking enterotoxic
      activity. This study dealt with CdB, providing the first evidence that intestinal
      cells exposed to this toxin exhibit typical features of apoptosis in that a
      significant proportion of the treated cells displayed nuclear fragmentation and
      chromatin condensation. In keeping with ultrastructural data, CdB-treated cells
      showed the typical flow cytometric hallmark of apoptosis consisting of a distinct
      sub-G1 peak. The CdB-induced apoptotic response was dose and time dependent and
      not simply due to the actin-disrupting effect of the toxin or to the subsequent
      impairment of cell anchorage. Rather, the inhibition of proteins belonging to the
      Rho family due to CdB seems to play a role in the induction of apoptosis in
      intestinal cells. The origin of cells and the growth rate may also be cofactors
      relevant to such a response.

PMID- 9596732
TI  - A fibrinogen-binding protein of Staphylococcus epidermidis.
AB  - The present study reports on fibrinogen (Fg) binding of Staphylococcus
      epidermidis. Adhesion of different S. epidermidis strains to immobilized Fg was
      found to vary significantly between different strains, and the component
      responsible was found to be proteinaceous in nature. To further characterize the
      Fg-binding activity, a shotgun phage display library covering the S. epidermidis
      chromosome was constructed. By affinity selection (panning) against immobilized
      Fg, a phagemid clone, pSEFG1, was isolated, which harbors an insert with an open
      reading frame of approximately 1.7 kilobases. Results from binding and inhibition
      experiments demonstrated that the insert of pSEFG1 encodes a specific Fg-binding
      protein. Furthermore, affinity-purified protein encoded by pSEFG1 completely
      inhibited adhesion of S. epidermidis to immobilized Fg. By additional cloning and
      DNA sequence analyses, the complete gene, termed fbe, was found to consist of an
      open reading frame of 3,276 nucleotides encoding a protein, called Fbe, with a
      deduced molecular mass of approximately 119 kDa. With a second phage display
      library made from another clinical isolate of S. epidermidis, it was possible to
      localize the Fg-binding region to a 331-amino-acid-long fragment. PCR analysis
      showed that the fbe gene was found in 40 of 43 clinical isolates of S.
      epidermidis. The overall organization of Fbe resembles those of other
      extracellular surface proteins of staphylococci and streptococci. Sequence
      comparisons with earlier known proteins revealed that this protein is related to
      an Fg-binding protein of Staphylococcus aureus called clumping factor.

PMID- 9596733
TI  - Decorin-binding protein of Borrelia burgdorferi is encoded within a two-gene
      operon and is protective in the murine model of Lyme borreliosis.
AB  - Isolated outer membranes of Borrelia burgdorferi were used in immunoblotting
      experiments with sera from immune mice to identify new putative Lyme disease
      vaccine candidates. One immunoreactive polypeptide migrated on polyacrylamide
      gels just proximal to outer surface protein C and comigrated with [3H]palmitate
      labeled polypeptides. A degenerate oligonucleotide primer based upon internal
      amino acid sequence information was used to detect the corresponding gene within
      a B. burgdorferi total genomic library. The relevant open reading frame (ORF)
      encoded a polypeptide comprised of a 24-amino-acid putative signal peptide
      terminated by LLISC, a probable consensus sequence for lipoprotein modification,
      and a mature protein of 163 amino acids. Immunoblots of a recombinant fusion
      protein corresponding to this ORF supported the idea that the encoded protein was
      a previously reported decorin-binding protein (DBP) of B. burgdorferi N40 (B. P.
      Guo, S. J. Norris, L. C. Rosenberg, and M. Hook, Infect. Immun. 63:3467-3472,
      1995). However, further DNA sequencing revealed the presence of a second ORF,
      designated ORF-1, whose termination codon was 119 bp upstream of the dbp gene.
      ORF-1 also encoded a putative lipoprotein with a mature length of 167 amino
      acids. Northern blots, Southern blots, and primer extension analyses indicated
      that ORF-1 and dbp comprised a two-gene operon located on the 49-kb linear
      plasmid. Both proteins, which were 40% identical and 56% similar, partitioned
      into Triton X-114 detergent extracts of B. burgdorferi isolated outer membranes.
      Mice infected with B. burgdorferi produced high titers of antibodies against the
      ORF-1-encoded protein and DBP during both early and later stages of chronic
      infection. Both DBP and the ORF-1-encoded protein were sensitive to proteinase K
      treatment of intact borreliae, suggesting that they were surface exposed. In
      active immunization experiments, 78% of mice immunized with recombinant DBP were
      immune to challenge. While it is not clear whether the two lipoproteins encoded
      by the ORF-1-dbp operon have analogous decorin-binding functions in vivo, the
      combined studies implicate DBP as a new candidate for a human Lyme disease
      vaccine.

PMID- 9596734
TI  - Molecular and immunological analyses of the Mycobacterium avium homolog of the
      immunodominant Mycobacterium leprae 35-kilodalton protein.
AB  - The analysis of host immunity to mycobacteria and the development of
      discriminatory diagnostic reagents relies on the characterization of conserved
      and species-specific mycobacterial antigens. In this report, we have
      characterized the Mycobacterium avium homolog of the highly immunogenic M. leprae
      35-kDa protein. The genes encoding these two proteins were well conserved, having
      82% DNA identity and 90% identity at the amino acid level. Moreover both
      proteins, purified from the fast-growing host M. smegmatis, formed multimeric
      complexes of around 1000 kDa in size and were antigenically related as assessed
      through their recognition by antibodies and T cells from M. leprae-infected
      individuals. The 35-kDa protein exhibited significant sequence identity with
      proteins from Streptomyces griseus and the cyanobacterium Synechoccocus sp.
      strain PCC 7942 that are up-regulated under conditions of nutrient deprivation.
      The 67% amino acid identity between the M. avium 35-kDa protein and SrpI of
      Synechoccocus was spread across the sequences of both proteins, while the
      homologous regions of the 35-kDa protein and the P3 sporulation protein of S.
      griseus were interrupted in the P3 protein by a divergent central region.
      Assessment by PCR demonstrated that the gene encoding the M. avium 35-kDa protein
      was present in all 30 M. avium clinical isolates tested but absent from M.
      intracellulare, M. tuberculosis, or M. bovis BCG. Mice infected with M. avium,
      but not M. bovis BCG, developed specific immunoglobulin G antibodies to the 35
      kDa protein, consistent with the observation that tuberculosis patients do not
      recognize the antigen. Strong delayed-type hypersensitivity was elicited by the
      protein in guinea pigs sensitized with M. avium.

PMID- 9596736
TI  - Indications of the protective role of natural killer cells in human cutaneous
      leishmaniasis in an area of endemicity.
AB  - The role of natural versus acquired immunity to Leishmania aethiopica infection
      in humans is the focus of our studies. We found in previous studies that
      mononuclear cells from nonexposed healthy Swedish donors responded to Leishmania
      antigen stimulation by proliferation and gamma interferon production. The main
      cell type responding was CD3- CD16/56+ natural killer (NK) cells. These findings
      led us to suggest that the potential to produce a rapid, nonacquired NK cell
      response may be a protective phenotype. In order to test this hypothesis, an area
      in Ethiopia where Leishmania is endemic was selected, and peripheral blood
      mononuclear cells were obtained from individuals who had lived in the area most
      of their lives but had no evidence of past or present leishmaniasis. Their
      responses were compared with those of confirmed leishmaniasis patients from the
      same region with active lesions or cured leishmaniasis lesions. Cells from these
      donors were stimulated in vitro with L. aethiopica antigen. Responses were
      measured by proliferation, cytokine production, and phenotype analysis by
      fluorescence-activated cell sorting. The association of NRAMP1 alleles with the
      studied phenotype and susceptibility to L. aethiopica-induced leishmaniasis was
      also evaluated. The results show that Leishmania antigens can induce NK cell and
      CD8+-T-cell responses in vitro. This is clearly seen in proliferating cells from
      the cured (immune) individuals and the apparently protected controls from the
      area of endemicity. It contrasted with the reactivity of the patients, where some
      NK proliferation was coupled with enhanced CD4+-T-cell proliferation. We conclude
      from these observations that NK cells and CD8(+) cells proliferating in response
      to Leishmania stimulation are involved in protection from and healing of
      (Ethiopian) cutaneous leishmaniasis; however, such mechanisms appear to be
      unrelated to the NRAMP1 host resistance gene.

PMID- 9596735
TI  - Borrelia burgdorferi stimulates the production of interleukin-10 in peripheral
      blood mononuclear cells from uninfected humans and rhesus monkeys.
AB  - Heat-killed Borrelia burgdorferi spirochetes stimulate in vitro production of
      interleukin-10 (IL-10) at both mRNA and protein levels in peripheral blood
      mononuclear cells (PBMC) of uninfected rhesus monkeys. A concomitant down
      modulation of IL-2 gene transcription was observed. Neither IL-4 nor gamma
      interferon gene expression was ostensibly affected by B. burgdorferi spirochetes.
      These phenomena were observed regardless of whether the stimulating spirochetes
      belonged to the B. burgdorferi sensu stricto, Borrelia afzelii, or Borrelia
      garinii genospecies, the three main species that cause Lyme disease. B.
      burgdorferi also induced production of IL-10 in uninfected human PBMC, indicating
      that this effect might play a role in human Lyme disease. Purified lipidated
      outer surface protein A (OspA), but not its unlipidated form, induced the
      production of high levels of IL-10 in uninfected human PBMC. Thus, the lipid
      moiety is essential in the induction of IL-10 in these PBMC. B. burgdorferi M297,
      a mutant strain that lacks the plasmid that encodes OspA and OspB, also induced
      IL-10 gene transcription in PBMC, indicating that this phenomenon is not causally
      linked exclusively to OspA and its lipid moiety. These results demonstrate that
      B. burgdorferi can stimulate the production of an antiinflammatory,
      immunosuppressive cytokine in naive cells and suggest that IL-10 may play a role
      both in avoidance by the spirochete of deleterious immune responses and in
      limiting the inflammation that the spirochete is able to induce.

PMID- 9596737
TI  - Antibody-secreting cells in the stomachs of symptomatic and asymptomatic
      Helicobacter pylori-infected subjects.
AB  - In this study we analyzed whether infection with Helicobacter pylori gives rise
      to specific B-cell responses against a number of putative virulence factors of H.
      pylori, e.g., urease, flagellin, and different bacterial surface antigens,
      locally in the gastric mucosa. This was studied in antrum and corpus biopsies
      collected from 11 H. pylori-infected patients with duodenal ulcers, 11
      asymptomatic H. pylori carriers, and 13 noninfected, healthy controls.
      Mononuclear cells were isolated from the biopsies and assayed for frequencies of
      total and H. pylori-specific antibody-secreting cells (ASCs) by means of the
      enzyme-linked immunospot technique. The H. pylori-infected subjects had
      remarkably higher frequencies of total immunoglobulin A (IgA)- and IgM-secreting
      cells than the noninfected subjects, while the frequencies of IgG-secreting cells
      were virtually the same in the different groups. In addition, most of the
      infected subjects had IgA ASCs reacting with H. pylori membrane proteins,
      flagellin, and urease, while none of the noninfected subjects had any detectable
      H. pylori-reactive ASCs. Furthermore, half of the infected subjects also had ASCs
      reacting with a Helicobacter-specific 26-kDa protein, while only a few of them
      had ASCs reacting with neutrophil-activating protein, the neuraminyllactose
      binding hemagglutinin HpaA, or lipopolysaccharides purified from different H.
      pylori strains. The frequencies of H. pylori-specific ASCs in the antrum and
      corpus were almost identical, and no differences in either antigen specificity or
      magnitude of the B-cell response in the stomach could be detected between the
      ulcer patients and the asymptomatic H. pylori carriers. This study demonstrates
      that H. pylori infection induces strong antibody responses in the human gastric
      mucosa, both in asymptomatic carriers and in duodenal ulcer patients. However,
      the outcome of infection could not be explained by differences in the local B
      cell response to any of the antigens used in this study.

PMID- 9596738
TI  - Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in
      hyphal development and systemic candidiasis.
AB  - Extracellular signal-regulated protein kinase (ERK, or mitogen-activated protein
      kinase [MAPK]) regulatory cascades in fungi turn on transcription factors that
      control developmental processes, stress responses, and cell wall integrity. CEK1
      encodes a Candida albicans MAPK homolog (Cek1p), isolated by its ability to
      interfere with the Saccharomyces cerevisiae MAPK mating pathway. C. albicans
      cells with a deletion of the CEK1 gene are defective in shifting from a
      unicellular budding colonial growth mode to an agar-invasive hyphal growth mode
      when nutrients become limiting on solid medium with mannitol as a carbon source
      or on glucose when nitrogen is severely limited. The same phenotype is seen in C.
      albicans mutants in which the homologs (CST20, HST7, and CPH1) of the S.
      cerevisiae STE20, STE7, and STE12 genes are disrupted. In S. cerevisiae, the
      products of these genes function as part of a MAPK cascade required for mating
      and invasiveness of haploid cells and for pseudohyphal development of diploid
      cells. Epistasis studies revealed that the C. albicans CST20, HST7, CEK1, and
      CPH1 gene products lie in an equivalent, canonical, MAPK cascade. While Cek1p
      acts as part of the MAPK cascade involved in starvation-specific hyphal
      development, it may also play independent roles in C. albicans. In contrast to
      disruptions of the HST7 and CPH1 genes, disruption of the CEK1 gene adversely
      affects the growth of serum-induced mycelial colonies and attenuates virulence in
      a mouse model for systemic candidiasis.

PMID- 9596739
TI  - Effects of granulocyte-macrophage colony-stimulating factor and tumor necrosis
      factor alpha on Trypanosoma cruzi trypomastigotes.
AB  - We have previously shown that the addition of exogenous granulocyte-macrophage
      colony-stimulating factor (GM-CSF) to nonactivated mouse peritoneal macrophages
      (MPM) limits Trypanosoma cruzi infections in vitro (E. Olivares Fontt and B.
      Vray, Parasite Immunol. 17:135-141, 1995). Lower levels of infection were
      correlated with a higher level of production of tumor necrosis factor alpha (TNF
      alpha) in the absence of nitric oxide (NO) release. These data suggested that GM
      CSF and/or TNF-alpha might have a direct parasitocidal effect on T. cruzi
      trypomastigotes, independently of NO release. To address this question, T. cruzi
      trypomastigotes were treated with recombinant murine GM-CSF (rmGM-CSF),
      recombinant murine TNF-alpha (rmTNF-alpha), or both cytokines in a cell-free
      system. Treatment with rmGM-CSF but not rmTNF-alpha caused morphological changes
      in the parasites, and most became spherical after 7 h of incubation. Both
      cytokines exerted a cytolytic activity on the trypomastigotes, yet the
      trypanolytic activity of rmTNF-alpha was more effective than that of rmGM-CSF.
      Viable rmGM-CSF- and rmTNF-alpha-treated parasites were less able to infect MPM
      than untreated parasites, and this reduction in infectivity was greatest for rmGM
      CSF. Treatments with both cytokines resulted in more lysis and almost complete
      inhibition of infection. The direct parasitocidal activity of rmTNF-alpha was
      inhibited by carbohydrates and monoclonal antibodies specific for the lectin-like
      domain of TNF-alpha. Collectively, these results suggest that cytokines such as
      GM-CSF and TNF-alpha may directly control the level of T. cruzi trypomastigotes
      at least in vitro and so could determine the outcome of infection in vivo.

PMID- 9596740
TI  - Identification and characterization of a 29-kilodalton protein from Mycobacterium
      tuberculosis culture filtrate recognized by mouse memory effector cells.
AB  - Culture filtrate proteins from Mycobacterium tuberculosis induce protective
      immunity in various animal models of tuberculosis. Two molecular mass regions (6
      to 10 kDa and 24 to 36 kDa) of short-term culture filtrate are preferentially
      recognized by Th1 cells in animal models as well as by patients with minimal
      disease. In the present study, the 24- to 36-kDa region has been studied, and the
      T-cell reactivity has been mapped in detail. Monoclonal antibodies were
      generated, and one monoclonal antibody, HYB 71-2, with reactivity against a 29
      kDa antigen located in the highly reactive region below the antigen 85 complex
      was selected. The 29-kDa antigen (CFP29) was purified from M. tuberculosis short
      term culture filtrate by thiophilic adsorption chromatography, anion-exchange
      chromatography, and gel filtration. In its native form, CFP29 forms a polymer
      with a high molecular mass. CFP29 was mapped in two-dimensional electrophoresis
      gels as three distinct spots just below the antigen 85 complex component MPT59.
      CFP29 is present in both culture filtrate and the membrane fraction from M.
      tuberculosis, suggesting that this antigen is released from the envelope to
      culture filtrate during growth. Determination of the N-terminal amino acid
      sequence allowed cloning and sequencing of the cfp29 gene. The nucleotide
      sequence showed 62% identity to the bacteriocin Linocin from Brevibacterium
      linens. Purified recombinant histidine-tagged CFP29 and native CFP29 had similar
      T-cell stimulatory properties, and they both elicited the release of high levels
      of gamma interferon from mouse memory effector cells isolated during the recall
      of protective immunity to tuberculosis. Interspecies analysis by immunoblotting
      and PCR demonstrated that CFP29 is widely distributed in mycobacterial species.

PMID- 9596741
TI  - Strain-dependent activation of monocytes and inflammatory macrophages by
      lipopolysaccharide of Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is one of the pathogens associated with periodontal
      diseases, and its lipopolysaccharide (LPS) has been suggested as a possible
      virulence factor, acting by stimulation of host cells to secrete proinflammatory
      mediators. However, recent studies have shown that P. gingivalis LPS inhibited
      some components of the inflammatory response. The present study was designed to
      test the hypothesis that there are strain-dependent variations in the ability of
      P. gingivalis LPS to elicit the host inflammatory response. By using LPS
      preparations from two strains of P. gingivalis, W50 and A7346, the responses of
      mouse macrophages and human monocytes were evaluated by measuring the secretion
      of nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha). Both direct and
      indirect (priming) effects were investigated. LPS from Salmonella typhosa was
      used as a reference LPS. P. gingivalis A7436 LPS induced lower secreted levels of
      NO from the tested cells than S. typhosa LPS but induced similar levels of TNF
      alpha. In contrast, LPS from P. gingivalis W50 did not induce NO or TNF-alpha
      secretion. Preincubation of macrophages with LPS from S. typhosa or P. gingivalis
      A7436 prior to stimulation with S. typhosa LPS upregulated NO secretion and
      downregulated TNF-alpha secretion, while preincubation with P. gingivalis W50 LPS
      enhanced both TNF-alpha and NO secretory responses. These results demonstrate
      that LPSs derived from different strains of P. gingivalis vary in their
      biological activities in vitro. The findings may have an impact on our
      understanding of the range of P. gingivalis virulence in vivo.

PMID- 9596742
TI  - Genetic and biochemical analysis of mutacin 1140, a lantibiotic from
      Streptococcus mutans.
AB  - Streptococcus mutans JH1000 and its derivatives were previously shown (J. D.
      Hillman, K. P. Johnson, and B. I. Yaphe, Infect. Immun. 44:141-144, 1984) to
      produce a low-molecular-weight, broad-spectrum bacteriocin-like inhibitory
      substance (BLIS). The thermosensitive vector pTV1-OK harboring Tn917 was used to
      isolate a BLIS-deficient mutant, DM25, and the mutated gene was recovered by
      shotgun cloning in Escherichia coli. Sequence analysis of insert DNA adjacent to
      Tn917 led to the identification of four open reading frames including two (lanA
      and lanB) which have substantial homology to the Staphylococcus epidermidis
      structural gene (epiA) and a modifying enzyme gene (epiB) for biosynthesis of the
      lantibiotic epidermin, respectively. Although the BLIS activity could not be
      recovered from broth cultures, high yields were obtained from a solid medium
      consisting of Todd-Hewitt broth containing 0.5% agarose that was stab inoculated
      with JH1140 (a spontaneous mutant of JH1000 that produces threefold-elevated
      amounts of activity). Agar could not substitute for agarose. Chloroform
      extraction of the spent medium produced a fraction which yielded two major bands
      on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The faster
      migrating band was absent in chloroform extracts of the mutant, DM25. The amino
      acid sequence of this band was determined by Edman sequencing and mass
      spectroscopy. The results showed that it is a lantibiotic, which we have named
      mutacin 1140, and that the sequence corresponded to that deduced from the lanA
      sequence. We observed a number of similarities of mutacin 1140 to epidermin and
      an S. mutans lantibiotic, B-Ny266, but it appears to have significant differences
      in the positions of its thioether bridges. It also has other unique features with
      regard to its leader sequence and posttranslational modification. A proposed
      structure for mutacin 1140 is presented.

PMID- 9596743
TI  - Augmentation of human macrophage candidacidal capacity by recombinant human
      myeloperoxidase and granulocyte-macrophage colony-stimulating factor.
AB  - Phagocyte myeloperoxidase (MPO) is believed to be particularly important in
      defense against candida infection. We reported earlier that monocytes, rich in
      MPO, killed Candida albicans at a significantly higher rate and extent than did
      monocyte-derived macrophages, known to lack MPO, and that C. albicans is less
      resistant to MPO-dependent oxidants than less pathogenic Candida species. We
      hypothesized, therefore, that the capacity of macrophages to kill C. albicans
      might be improved in the presence of MPO. In this study, we evaluated the ability
      of recombinant human MPO (rhMPO) to augment the killing of C. albicans by
      resident macrophages and macrophages activated by recombinant human granulocyte
      macrophage colony-stimulating factor. Addition of rhMPO (concentration range, 0.8
      to 6.4 U/ml) to suspensions of resident and activated macrophages and opsonized
      C. albicans resulted in concentration-dependent and significant increases in
      candida killing. This enhancement was particularly pronounced with activated
      macrophages, whether C. albicans was opsonized or unopsonized and ingested
      through the macrophage mannose receptor. rhMPO did not affect the killing of C.
      albicans by monocytes, nor did it affect phagocytosis of opsonized or unopsonized
      C. albicans. These results indicate that exogenous rhMPO can augment the
      candidacidal capacity of both resident and activated macrophages, with a more
      profound effect on activated cells. We suggest that rhMPO may be effective in the
      treatment of invasive candidiasis.

PMID- 9596744
TI  - Effects of toxin A from Clostridium difficile on mast cell activation and
      survival.
AB  - Toxins A and B from Clostridium difficile are the main cause of antibiotic
      associated diarrhea and pseudomembranous colitis. They cause fluid accumulation,
      necrosis, and a strong inflammatory response when inoculated in intestinal loops.
      Since mast cells are a rich source of inflammatory mediators, abundant in the
      gut, and known to be involved in C. difficile-induced enteritis, we studied the
      in vitro effect of toxin A on isolated mast cells. Normal rats sensitized by
      infection with Nippostrongilus brasiliensis were used to isolate peritoneal mast
      cells (PMC). PMC from naive rats were stimulated with calcium ionophore A23187 as
      a model of antigen-independent activation, and PMC from sensitized rats were
      stimulated with N. brasiliensis antigens to study immunoglobulin E-dependent mast
      cell activation. After 4 h, toxin A did not induce release of nitric oxide or
      histamine in naive PMC. However, 10 ng of toxin per ml caused a significant
      release of tumor necrosis factor alpha (TNF-alpha). In contrast, 1 microg of
      toxin per ml inhibited antigen or A23187-induced histamine release by PMC. Toxin
      A at 1 microg/ml for 4 h caused disruption of actin which aggregated in the
      cytoplasm and around the nucleus. After 24 h, chromatin condensation, cytoplasmic
      blebbing, and apoptotic-like vesicles were observed; DNA fragmentation was
      documented also. These results suggest that mast cells may participate in the
      initial inflammatory response to C. difficile infection by releasing TNF-alpha
      upon interaction with toxin A. However, longer exposure to toxin A affects the
      release of inflammatory mediators, perhaps because of the alteration of the
      cytoskeleton and induction of apoptosis. The impaired functions and survival of
      mast cells by C. difficile toxin A could hamper the capacity of these cells to
      counteract the infection, thus prolonging the pathogenic effects of C. difficile
      toxins.

PMID- 9596745
TI  - Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for
      respiratory infection in mice.
AB  - In Bordetella species, the BvgAS sensory transduction system mediates an
      alteration between the Bvg+ phase, characterized by expression of adhesins and
      toxins, and the Bvg- phase, characterized by the expression of motility and
      coregulated phenotypes in Bordetella bronchiseptica and by the expression of vrg
      loci in Bordetella pertussis. Since there is no known environmental or animal
      reservoir for B. pertussis, the causative agent of whooping cough, it has been
      assumed that this phenotypic alteration must occur within the human host during
      infection. Consistent with this hypothesis was the observation that a B.
      pertussis mutant, SK6, containing a TnphoA insertion mutation in a Bvg-repressed
      gene (vrg6) was defective for tracheal and lung colonization in a mouse model of
      respiratory infection (D. T. Beattie, R. Shahin, and J. Mekalanos, Infect. Immun.
      60:571-577, 1992). This result was inconsistent, however, with the observation
      that a Bvg+ phase-locked B. bronchiseptica mutant was indistinguishable from the
      wild type in its ability to establish a persistent respiratory infection in
      rabbits and rats (P. A. Cotter and J. F. Miller, Infect. Immun. 62:3381-3390,
      1994; B. J. Akerley, P. A. Cotter, and J. F. Miller, Cell 80:611-620, 1995). To
      directly address the role of Bvg-mediated signal transduction in B. pertussis
      pathogenesis, we constructed Bvg+ and Bvg- phase-locked mutants and compared them
      with the wild type for their ability to colonize the respiratory tracts of mice.
      Our results show that the Bvg+ phase of B. pertussis is necessary and sufficient
      for respiratory infection. By constructing a strain with a deletion in the bvgR
      regulatory locus, we also show that ectopic expression of Bvg- phase phenotypes
      decreases the efficiency of colonization, underscoring the importance of Bvg
      mediated repression of gene expression in vivo. Finally, we show that the
      virulence defect present in strain SK6 cannot be attributed to the vrg6 mutation.
      These data contradict an in vivo role for the Bvg- phase of B. pertussis.

PMID- 9596746
TI  - Characterization of mannose receptor-dependent phagocytosis mediated by
      Mycobacterium tuberculosis lipoarabinomannan.
AB  - The macrophage mannose receptor (MR) along with complement receptors mediates
      phagocytosis of the M. tuberculosis virulent strains Erdman and H37Rv. We have
      determined that the terminal mannosyl units of the M. tuberculosis surface
      lipoglycan, lipoarabinomannan (LAM), from the Erdman strain serve as ligands for
      the MR. The biology of the MR (receptor binding and trafficking) in response to
      phagocytic stimuli is not well characterized. This study analyzes the MR
      dependent phagocytosis mediated by Erdman LAM presented on a 1-micron-diameter
      phagocytic particle. Erdman LAM microspheres exhibited a time- and dose-dependent
      rapid increase in attachment and internalization by human monocyte-derived
      macrophages (MDMs). In contrast, internalization of LAM microspheres by monocytes
      was minimal. Microsphere internalization by MDMs was visualized and quantitated
      by immunofluorescence and confocal and electron microscopy and resembled
      conventional phagocytosis. Phagocytosis of LAM microspheres by MDMs was energy,
      cytoskeleton, and calcium dependent and was mannan inhibitable. Trypsin treatment
      of MDMs at 37 degrees C, which depleted surface and recycling intracellular pools
      of the MR, reduced the subsequent attachment of LAM microspheres. Trypsin
      treatment at 4 degrees C allowed for subsequent recovery of LAM microsphere
      phagocytosis at 37 degrees C by recycled MRs. Pretreatment of MDMs with
      cycloheximide influenced LAM microsphere phagocytosis to only a small extent,
      indicating that MR-dependent phagocytosis of the microspheres was occurring
      primarily by preformed recycled receptors. This study characterizes the
      requirements for macrophage phagocytosis of a LAM-coated particle mediated by the
      MR. This model will be useful in further characterization of the intracellular
      pathway taken by phagocytic particles coated with different LAM types in
      macrophages following ingestion.

PMID- 9596747
TI  - The abilities of a Staphylococcus epidermidis wild-type strain and its slime
      negative mutant to induce endocarditis in rabbits are comparable.
AB  - The abilities of a parent and mutant pair of Staphylococcus epidermidis strains,
      the slime-producing parent RP62A and its slime-negative mutant, to establish
      endocarditis in a rabbit model of aortic valve endocarditis and to accumulate and
      adhere to surfaces in vitro were compared. Vegetation titer and infection rate
      depended on the presence or absence of a catheter (P = 0.020) and on inoculum
      size (P < 0.001) but not on the infecting strain. The ability of the parent
      strain vis-a-vis its mutant to accumulate in vitro on surfaces as demonstrated in
      a slime test did not correlate with any enhancement in the development of
      endocarditis in the rabbit model. In vitro initial adherence rates were
      identical. Both isolates accumulated to the same reduced extent in vitro in the
      presence of serum, albumin, or gelatin. Adhesion was equally promoted by addition
      of fibronectin. These data suggest that the in vitro phenomenon of accumulation
      described as slime production in the absence of serum may not be an important
      virulence determinant in vivo.

PMID- 9596748
TI  - Expanded CD14+ CD16+ monocyte subpopulation in patients with acute and chronic
      infections undergoing hemodialysis.
AB  - Infections are frequent complications in end-stage renal failure patients
      undergoing hemodialysis (HD), and peripheral blood monocytes are important cells
      in host defense against infections. The majority of circulating monocytes express
      high levels of lipopolysaccharide receptor antigen CD14 and are negative for the
      immunoglobulin Fcgamma receptor type III (CD16). We studied the occurrence of a
      minor subpopulation coexpressing low levels of CD14 together with CD16 in HD
      patients. In healthy controls CD14+ CD16+ monocytes account for 8% +/- 4% of
      CD14+ monocytes, with an absolute number of 29 +/- 14 cells/microl. In stable HD
      patients the CD14+ CD16+ subpopulation was significantly elevated (14% +/- 3%, or
      66 +/- 28 cells/microl), while the number of CD14(++) monocytes (monocytes
      strongly positive for CD14) remained constant. In HD patients suffering from
      chronic infections a further rise in CD14+ CD16+ monocytes was observed (128 +/-
      71 cells/microl; P < 0.01) such that this subpopulation constituted 24% of all
      blood monocytes. In contrast, numbers of CD14++ cells did not change compared to
      those for stable HD patients, indicating that the CD14+ CD16+ monocyte
      subpopulation was selectively expanded. During acute infections the CD14+ CD16+
      cell subpopulation always expanded. A whole-blood assay revealed that CD14+ CD16+
      monocytes exhibited a higher phagocytosis rate for Escherichia coli bacteria than
      CD14++ monocytes, underlining their role during host defense. In addition, CD14+
      CD16+ monocytes expressed higher levels of major histocompatibility complex (MHC)
      class II antigens (HLA-DR, -DP, and -DQ) and equal amounts of MHC class I
      antigens (HLA-ABC). Thus, CD14+ CD16+ cells constitute a potent phagocytosing and
      antigen-presenting monocyte subpopulation, which is expanded during acute and
      chronic infections commonly observed in chronic HD patients.

PMID- 9596749
TI  - Secretory phospholipase A2 is the principal bactericide for staphylococci and
      other gram-positive bacteria in human tears.
AB  - We examined human tears for molecules that killed gram-positive bacteria. The
      principal mediator of bactericidal activity against staphylococci proved to be a
      calcium-dependent enzyme, secretory phospholipase A2. Whereas the concentration
      of secretory phospholipase A2 in the normal tear film exceeded 30 microg/ml, only
      1.1 ng (<0.1 nM) of the enzyme per ml sufficed to kill Listeria monocytogenes and
      15 to 80 ng/ml killed Staphylococcus aureus. Despite its efficacy against gram
      positive bacteria, secretory phospholipase A2 lacked bactericidal activity
      against gram-negative organisms (Escherichia coli, Salmonella typhimurium, and
      Pseudomonas aeruginosa) when tested in the ionic environment of tears. Given the
      presence of secretory phospholipase A2 in tears, intestinal secretions, and
      leukocytes, this enzyme may play a substantial role in innate mucosal and
      systemic bactericidal defenses against gram-positive bacteria.

PMID- 9596750
TI  - Time course and host responses to Escherichia coli urinary tract infection in
      genetically distinct mouse strains.
AB  - Recurrent urinary tract infections (UTIs) are a significant clinical problem for
      many women; however, host susceptibility factors have not been completely
      defined. The mouse model of induced UTI provides an experimental environment in
      which to identify specific host characteristics that are important in initial
      bacterial colonization of the urinary tract and in resolution of an infection.
      This study examined initial susceptibility, bacterial clearance, and host defense
      mechanisms during induction and resolution of Escherichia coli UTIs in
      genetically distinct strains of mice. Of the ten inbred strains tested, six
      (BALB/c, C3H/HeN, C57BL/6, DBA.1, DBA.2, and AKR) showed progressive resolution
      of bladder infections over a 14-day period. A constant, low-level bladder
      infection was observed in SWR and SJL mice. High bladder infection levels
      persisted over the 14-day study period in C3H/HeJ and C3H/OuJ mice. Kidney
      infection levels generally correlated with bladder infection levels, especially
      in C3H/HeJ and C3H/OuJ mice, the two most susceptible strains, in which
      infections became more severe with time after challenge. The degree of
      inflammation in bladder and kidneys, as well as antibody-forming cell responses,
      positively correlated with infection intensity in all strains except C3H/HeJ,
      which had minimal inflammation despite high infection levels. These results
      demonstrate two important aspects of host defense against UTI. First, the innate
      immune response to an infection in the bladder or kidneys consists primarily of
      local inflammation, which is followed by an adaptive response characterized in
      part by an antibody response to the infecting bacteria. Second, a UTI will be
      spontaneously resolved in most cases; however, in mice with specific genetic
      backgrounds, a UTI can persist for an extended length of time. The latter result
      strongly suggests that the presence or absence of specific host genes will
      determine how effectively an E. coli UTI will be resolved.

PMID- 9596751
TI  - Multiple fimbrial adhesins are required for full virulence of Salmonella
      typhimurium in mice.
AB  - Adhesion is an important initial step during bacterial colonization of the
      intestinal mucosa. However, mutations in the Salmonella typhimurium fimbrial
      operons lpf, pef, or fim only moderately alter mouse virulence. The respective
      adhesins may thus play only a minor role during infection or S. typhimurium may
      encode alternative virulence factors that can functionally compensate for their
      loss. To address this question, we constructed mutations in all four known
      fimbrial operons of S. typhimurium: fim, lpf, pef, and agf. A mutation in the
      agfB gene resulted in a threefold increase in the oral 50% lethal dose (LD50) of
      S. typhimurium for mice. In contrast, an S. typhimurium strain carrying mutations
      in all four fimbrial operons (quadruple mutant) had a 26-fold increased oral
      LD50. The quadruple mutant, but not the agfB mutant, was recovered in reduced
      numbers from murine fecal pellets, suggesting that a reduced ability to colonize
      the intestinal lumen contributed to its attenuation. These data are evidence for
      a synergistic action of fimbrial operons during colonization of the mouse
      intestine and the development of murine typhoid fever.

PMID- 9596752
TI  - A low concentration of ethanol reduces the chemiluminescence of human
      granulocytes and monocytes but not the tumor necrosis factor alpha production by
      monocytes after endotoxin stimulation.
AB  - The ability of polymorphonuclear neutrophils (PMNs) and monocytes (Mphi) to
      produce reactive oxygen species (ROS) has been related closely to their potential
      in the killing of microorganisms. Ethanol has been shown to impair the generation
      of ROS in these phagocytes after stimulation with some immunogens and to increase
      the susceptibility of alcohol abusers to infectious diseases. As endotoxemia is
      common in alcohol abusers, we investigated the effect of ethanol (21.7
      mmol/liter) on the luminol-amplified chemiluminescence of PMNs and Mphi after
      endotoxin stimulation and the release of tumor necrosis factor alpha (TNF-alpha)
      from Mphi. Further, the efficiency of ethanol to inactivate chemically generated
      ROS was tested. Significant stimulation of ROS release occurred at endotoxin
      concentrations of 1 ng/ml or higher in both PMNs and Mphi. Ethanol significantly
      suppressed the formation of ROS in both cell types, the decrease being more
      pronounced in Mphi (-73. 8%) than in PMNs (-45.7%). The correlations between
      endotoxin concentration and the amount of released ROS showed a dose-dependent,
      sigmoidal course. Concentrations of endotoxin necessary for half-maximum
      stimulation were nearly identical (6 to 8 ng/ml) in both PMNs and Mphi,
      independent of the presence of ethanol. In contrast to ROS formation, ethanol had
      no effect on the amount of TNF-alpha produced by endotoxin-stimulated Mphi.
      Ethanol was shown to be unable to decrease the levels of chemically generated ROS
      under physiological conditions. Therefore, ethanol cannot be assumed to be an
      "antioxidative" compound but rather seems to modify processes of endotoxin
      recognition, intracellular signal transduction, or metabolism.

PMID- 9596753
TI  - Listeria monocytogenes-infected hepatocytes are targets of major
      histocompatibility complex class Ib-restricted antilisterial cytotoxic T
      lymphocytes.
AB  - Subclinical infection of BALB/c mice with the intracellular bacterial pathogen
      Listeria monocytogenes results in the development of protective antilisterial
      immunity. L. monocytogenes can infect hepatocytes, and antilisterial cytotoxic T
      lymphocytes (CTL) lyse Listeria-infected hepatocytes in a major
      histocompatibility complex (MHC) class Ia-restricted manner. It remained to be
      determined whether L. monocytogenes-infected hepatocytes are susceptible to MHC
      class Ib-restricted cytolysis. In this study, we showed that hepatocytes express
      MHC class Ib molecule Qa-1(b) mRNA and protein. We further showed that Listeria
      infected hepatocytes are susceptible to MHC class Ib-restricted cytolysis, since
      C57BL/6-derived Listeria-infected hepatocytes were lysed by BALB/c-derived
      antilisterial CTL. These results establish that Listeria-infected hepatocytes are
      susceptible to cytolysis by MHC class Ib restricted Listeria-specific CTL.

PMID- 9596754
TI  - Experimental infection of pregnant ewes with Chlamydia pecorum.
AB  - Pregnant ewes were infected in midpregnancy with three isolates of Chlamydia
      pecorum derived from the feces of healthy lambs from three different farms. Oral
      infection, alone or together with Fasciola hepatica, did not result in tissue
      invasion, since all placental and fecal samples were negative for chlamydiae.
      Intravenous infection resulted in placental infection in 16 of 18 ewes in that
      chlamydiae were cultured from placentas or vaginal swabs. Two ewes bore dead
      lambs after a shortened gestation time. The chlamydiae isolated were all C.
      pecorum. There were no significant differences between the weights of the lambs
      from the infected groups and those from uninfected control ewes. Most ewes showed
      no serological evidence of infection by the complement fixation test; therefore,
      it is unlikely that the enteric subtype of C. pecorum is responsible for the
      cross-reactions sometimes seen in flocks being tested for C. psittaci infection.

PMID- 9596755
TI  - Intrapulmonary delivery of tumor necrosis factor agonist peptide augments host
      defense in murine gram-negative bacterial pneumonia.
AB  - Tumor necrosis factor alpha (TNF) has been shown to be an essential cytokine
      mediator of innate immunity in Klebsiella pneumonia. Recently, a TNF agonist
      peptide consisting of the 11-amino-acid TNF binding site (TNF70-80) has been
      shown to possess many of the leukocyte-activating properties of TNF without the
      associated toxicity when administered locally or systemically. Given the
      beneficial effects of TNF in gram-negative pneumonia, we hypothesize that the
      intratracheal (i.t.) administration of TNF70-80 would augment lung innate
      immunity in mice challenged with intrapulmonary Klebsiella pneumoniae. The
      administration of TNF70-80 i.t. to CBA/J mice 7 days prior to, but not
      concomitantly with, the i.t. delivery of 3 x 10(3) CFU of K. pneumoniae resulted
      in a marked increase in survival compared to that of animals receiving a control
      peptide i.t. In addition, pretreatment with TNF70-80 resulted in improved
      bacterial clearance, which occurred in association with enhanced lung
      myeloperoxidase activity (as a measure of lung polymorphonuclear leukocyte
      influx), and increased expression of the important activating cytokines TNF,
      macrophage inflammatory protein-2, interleukin-12, and gamma interferon compared
      that for animals receiving control peptide. Finally, the administration of TNF70
      80 intraperitoneally resulted in enhanced rather than decreased lethality of
      Klebsiella pneumonia compared to that for animals receiving either TNF70-80 or
      control peptide i.t. Our studies suggest that the intrapulmonary, but not
      systemic, administration of the TNF agonist peptide may serve as an important
      immunoadjuvant in the treatment of murine Klebsiella pneumonia.

PMID- 9596756
TI  - Humoral immunity to Borrelia burgdorferi N40 decorin binding proteins during
      infection of laboratory mice.
AB  - A Borrelia burgdorferi N40 genomic expression library was screened with serum
      from actively infected mice to identify gene products that elicit protective
      immunity. A clone that contained a putative bicistronic operon containing two
      genes that encoded 20- and 22-kDa lipoproteins was identified and sequenced.
      These genes showed homology with the genes encoding decorin binding proteins DbpB
      and DbpA, respectively, of B. burgdorferi 297 and B31. N40-dbpA DNA hybridized
      with B. burgdorferi N40 DNA on a single 48-kb linear plasmid. Homologous genes
      could be amplified under various degrees of stringency by PCR or hybridized by
      Southern blotting from B. burgdorferi sensu stricto N40 and B31, and from B.
      burgdorferi sensu lato PBi and 25015, but not PKo. Recombinant N40-DbpB and N40
      DbpA were reactive with antibody in serum from infected mice, and serum was more
      reactive against N40-DbpA than against B. burgdorferi N40 recombinant P39, OspC,
      or OspA. Sera from mice infected with B. burgdorferi sensu lato strains PKo and
      PBi were weakly reactive against N40-DbpB and N40-DbpA, and sera from mice
      infected with 25015 were moderately reactive, compared to sera from mice infected
      with B. burgdorferi N40. Hyperimmunization of mice with N40-DbpA, but not N40
      DbpB, induced protective immunity against syringe challenge with cultured B.
      burgdorferi N40. DbpA may therefore be one of the antigens responsible for
      eliciting protective antibody known to exist in serum from infected mice. DNA
      amplification and serology suggest that DbpB and DbpA are likely to have homologs
      throughout the B. burgdorferi sensu lato family, but they are likely to be
      heterogeneous.

PMID- 9596758
TI  - Expression of two members of the pMGA gene family of Mycoplasma gallisepticum
      oscillates and is influenced by pMGA-specific antibodies.
AB  - Certain monoclonal antibodies and polyclonal antisera directed to pMGA, the major
      protein of Mycoplasma gallisepticum, were tested for the ability to influence the
      surface phenotype of the cell population which resulted from their inclusion in
      growth medium. The polyclonal antiserum and one monoclonal antibody (MAb 66)
      resulted in an alteration of surface phenotype; specifically, populations of
      cells grown either on plates or in broth cultures which contained these reagents
      ceased the expression of pMGA and instead expressed an antigenically unrelated
      new polypeptide (p82). Upon the removal of antibody, the progeny of these cells
      regained pMGA expression and produced antigenically sectored colonies. The basis
      of this switch between pMGA+ and pMGA- states was shown to be transcriptional.
      The p82 polypeptide, the expression of which resulted from growth of cells in
      antibodies, was another member of the pMGA gene family and was located just
      downstream from the pMGA gene normally expressed by the M. gallisepticum cells
      used. Collectively the results of this work suggest that this organism has
      evolved an unusual means of altering the antigenic composition of its surface in
      response to antibodies or to other environmental cues.

PMID- 9596757
TI  - Pasteurella haemolytica A1-derived leukotoxin and endotoxin induce intracellular
      calcium elevation in bovine alveolar macrophages by different signaling pathways.
AB  - Leukotoxin and endotoxin derived from Pasteurella haemolytica serotype 1 are the
      primary virulence factors contributing to the pathogenesis of lung injury in
      bovine pneumonic pasteurellosis. Activation of bovine alveolar macrophages with
      endotoxin or leukotoxin results in the induction of cytokine gene expression,
      with different kinetics (H. S. Yoo, S. K. Maheswaran, G. Lin, E. L. Townsend, and
      T. R. Ames, Infect. Immun. 63:381-388, 1995; H. S. Yoo, B. S. Rajagopal, S. K.
      Maheswaran, and T. R. Ames, Microb. Pathog. 18:237-252, 1995). Furthermore,
      extracellular Ca2+ is required for leukotoxin-induced cytokine gene expression.
      However, the involvement of Ca2+ in endotoxin effects and the precise signaling
      mechanisms in the regulation of intracellular Ca2+ by leukotoxin and endotoxin
      are not known. In fura-2-acetoxymethyl ester-loaded alveolar macrophages,
      intracellular Ca2+ regulation by leukotoxin and endotoxin was studied by video
      fluorescence microscopy. Leukotoxin induced a sustained elevation of
      intracellular Ca2+ in a concentration-dependent fashion by influx of
      extracellular Ca2+ through voltage-gated channels. In the presence of fetal
      bovine serum, endotoxin elevated intracellular Ca2+ even in the absence of
      extracellular Ca2+. Leukotoxin-induced intracellular Ca2+ elevation was inhibited
      by pertussis toxin, inhibitors of phospholipases A2 and C, and the arachidonic
      acid analog 5,8,11,14-eicosatetraynoic acid. Intracellular Ca2+ elevation by
      endotoxin was inhibited by inhibitors of phospholipase C and protein tyrosine
      kinase, but not by pertussis toxin, or the arachidonic acid analog. To the best
      of our knowledge, this is the first report of Ca2+ signaling by leukotoxin
      through a G-protein-coupled mechanism involving activation of phospholipases A2
      and C and release of arachidonic acid in bovine alveolar macrophages. Ca2+
      signaling by endotoxin, on the other hand, involves activation of phospholipase C
      and requires tyrosine phosphorylation. The differences in the Ca2+ signaling
      mechanisms may underlie the reported temporal differences in gene expression
      during leukotoxin and endotoxin activation.

PMID- 9596759
TI  - The immunodominant Brugia malayi paramyosin as a marker of current infection with
      Wuchereria bancrofti adult worms.
AB  - The full-length cDNA sequence encoding Brugia malayi L3 paramyosin has been
      isolated by immunoscreening a cDNA library with a mouse antiserum raised against
      Wuchereria bancrofti L3 infective larvae. A recombinant truncated form of
      paramyosin was expressed as a glutathione S-transferase fusion protein and used
      to evaluate humoral responses of adults from a W. bancrofti-endemic area in
      French Polynesia according to their parasitological status. Immunoglobulin G4
      (IgG4) preferentially bound to paramyosin in W. bancrofti-parasitized
      individuals, in contrast to unparasitized individuals, who harbored neither
      microfilaria nor Og4C3 adult worm circulating antigen. Reduction of the anti
      paramyosin IgG4 titer following combined chemotherapy with diethylcarbamazine and
      ivermectin was significantly correlated with a reduction in the adult worm
      burden. This indicates that the presence of paramyosin-reactive IgG4 is
      associated with the presence of parasites and that reduction can be used as an
      immunological marker for W. bancrofti clearance.

PMID- 9596760
TI  - Liposomes containing lipid A serve as an adjuvant for induction of antibody and
      cytotoxic T-cell responses against RTS,S malaria antigen.
AB  - Encapsulation of soluble protein antigens in liposomes was previously shown to
      result in processing of antigen via the major histocompatibility complex class I
      pathway, as evidenced by costaining of the trans-Golgi region of murine bone
      marrow-derived macrophages (BMs) by fluorophore-labeled liposomal antigen and by
      a trans-Golgi-specific fluorescent lipid. Evidence is presented here that free or
      liposome-encapsulated RTS,S, a particulate malaria antigen consisting of
      hepatitis B particles coexpressed with epitopes from the Plasmodium falciparum
      circumsporozoite protein, also was localized in the trans-Golgi after incubation
      with BMs, suggesting processing by the class I pathway. An in vivo cytotoxic T
      lymphocyte (CTL) response was detected, however, only after immunization with
      RTS,S encapsulated in liposomes containing lipid A and not after immunization
      with free RTS,S or with RTS,S encapsulated in liposomes lacking lipid A.
      Therefore, intracellular delivery of antigen containing CTL epitopes to the Golgi
      of BMs does not necessarily result in a CTL response in vivo unless an additional
      adjuvant, such as liposomes containing lipid A, is utilized. Encapsulation of
      RTS,S in liposomes containing monophosphoryl lipid A (MPL) resulted in a dose
      dependent enhancement of the NANP-specific immunoglobulin G (IgG) antibody
      response compared to that of free RTS,S. The IgG1 and IgG2a subclasses
      predominated after immunization with RTS,S encapsulated in liposomes containing
      MPL. These results demonstrate that encapsulation of a lipid-containing
      particulate antigen, such as RTS, S, in liposomes containing lipid A can enhance
      both humoral and cellular immune responses.

PMID- 9596761
TI  - Isotypes and opsonophagocytosis of pneumococcus type 6B antibodies elicited in
      infants and adults by an experimental pneumococcus type 6B-tetanus toxoid
      vaccine.
AB  - Streptococcus pneumoniae is a major respiratory pathogen of infants, children,
      and the elderly. Polysaccharide vaccines have been useful in adult populations
      but do not elicit protective immunity in infants and young children. To enhance
      their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to
      proteins are being developed. In this study antibody levels and opsonic
      activities were compared in sera of infants and adults injected with pneumococcal
      polysaccharide type 6B (Pn6B) conjugated to tetanus toxoid (TT) (Pn6B-TT).
      Healthy infants were injected with Pn6B-TT; group A was injected at 3, 4, and 6
      months of age, and group B was injected at 7 and 9 months of age. A booster
      injection was given at 18 months. Adults were injected once. Antibodies were
      measured by enzyme-linked immunosorbent assay and radioimmunoassay, and their
      functional activities were measured by opsonophagocytosis of radiolabelled
      pneumococci. In adults, increases in immunoglobulin M (IgM), IgG, IgA, IgG1, and
      IgG2 to Pn6B were observed. Infants reached adult levels of IgG1 anti-Pn6B after
      the primary injections. After the booster injection the infant groups had total
      IgG- and IgM-Pn6B antibody levels similar to those of adults. After the booster
      injection, IgG1 was the dominant infant anti-Pn6B isotype and at a level higher
      than in vaccinated adults, but IgA and IgG2 antibodies remained at very low
      levels. Opsonic activity increased significantly after Pn6B-TT injections; the
      highest infant sera showed opsonic activity comparable to that of vaccinated
      adults. Overall, opsonic activity correlated best with total and IgG anti-Pn6B
      antibodies (r = 0.741, r = 0.653, respectively; n = 35) and was highest in sera
      with high levels of all Pn6B antibody isotypes. The results indicate the
      protective potential of a pneumococcal 6B polysaccharide protein conjugate
      vaccine for young infants.

PMID- 9596762
TI  - Characterization of a sar homolog of Staphylococcus epidermidis.
AB  - Coagulase-negative staphylococci are common nosocomial pathogens. A regulatory
      element, designated sar, partially controls exoprotein synthesis in coagulase
      positive Staphylococcus aureus by modulating the expression of another regulatory
      locus, called agr. We report here the cloning of a sar homolog in S. epidermidis.
      The major open reading frame within sar in S. epidermidis is highly homologous
      (84%) to the S. aureus SarA protein. Primer extension studies revealed three sar
      transcripts (0.64, 0.76, and 0.85 kb) initiated from three distinct promoters.
      The interpromoter region in S. epidermidis differs from its S. aureus
      counterpart, possibly suggesting target gene differences and a disparate pattern
      for sar activation. Remarkably, the S. epidermidis sar homolog interacts with an
      agr promoter fragment of S. aureus in gel shift assays. Additionally, S.
      epidermidis sar fragments could restore hemolysin production in an S. aureus sar
      mutant. As typical virulence determinants controlled by sar in S. aureus are not
      present in S. epidermidis, an examination of functional and structural
      similarities and divergence of sar in staphylococci will be of major interest.

PMID- 9596763
TI  - Rectal and intranasal immunizations with recombinant urease induce distinct local
      and serum immune responses in mice and protect against Helicobacter pylori
      infection.
AB  - To determine the optimal inductive sites for immunization against Helicobacter
      pylori infection, the protective efficacy of recombinant urease (rUre) was
      assessed for mice given the vaccine by either the oral (p.o.), intranasal (i.n.),
      or rectal route. When mice were immunized with rUre (25 microg p.o. or rectally
      or 10 microg i.n.) plus heat-labile toxin from Escherichia coli as the mucosal
      adjuvant, all routes afforded protection against challenge with H. pylori, as
      indicated by a significant reduction in gastric urease activity (P < 0.0005)
      compared to that of sham-immunized controls. Quantitative H. pylori culture of
      stomach tissue demonstrated a >97% reduction in bacterial burden in mice
      immunized by all routes (P < 0.05). Induction of antiurease immunoglobulin A
      (IgA) levels in gastric luminal secretions after p.o. immunization was greater
      than after i.n. administration (means, 6.0 and 1.02 ng/ml, respectively) and was
      dependent upon challenge with H. pylori. However, immunization by the rectal
      route resulted in the generation of the highest levels of gastric antiurease IgA
      (mean, 40. 89 ng/ml), which was detectable prior to challenge with H. pylori.
      Immunohistochemical staining of stomach tissue for cells secreting urease
      specific antibody and CD4(+) T cells showed levels of recruitment to be dependent
      upon challenge with H. pylori and equivalent for all routes. These results
      identify both the rectum and nasal passages as suitable inductive sites for
      urease immunization.

PMID- 9596764
TI  - Characterization of the type 3 fimbrial adhesins of Klebsiella strains.
AB  - The Klebsiella pneumoniae fimbrial adhesin, MrkD, mediates adherence to the
      basolateral surfaces of renal and pulmonary epithelia and to the basement
      membranes of tissues. Although all isolates possessing the MrkD adhesin mediate
      the agglutination, in vitro, of erythrocytes treated with tannic acid, the mrkD
      gene is not conserved within species. The ability of a plasmid-borne mrkD gene
      product to mediate binding to type V collagen is associated frequently with
      strains of K. oxytoca and rarely with strains of K. pneumoniae. In K. pneumoniae,
      the MrkD adhesin is located within a chromosomally borne gene cluster and
      mediates binding to collagen types IV and V. The plasmid-borne determinant,
      mrkD1P, and the chromosomally borne gene, mrkD1C, are not genetically related.
      Some strains of enterobacteria possess a mrkD1C allele that is associated with
      hemagglutinating activity but does not bind to either type IV or type V collagen.

PMID- 9596765
TI  - Characterization of protective epitopes in a highly conserved Plasmodium
      falciparum antigenic protein containing repeats of acidic and basic residues.
AB  - The delineation of putatively protective and immunogenic epitopes in vaccine
      candidate proteins constitutes a major research effort towards the development of
      an effective malaria vaccine. By virtue of its role in the formation of the
      immune clusters of merozoites, its location on the surface of merozoites, and its
      highly conserved nature both at the nucleotide sequence level and the amino acid
      sequence level, the antigen which contains repeats of acidic and basic residues
      (ABRA) of the human malaria parasite Plasmodium falciparum represents such an
      antigen. Based upon the predicted amino acid sequence of ABRA, we synthesized
      eight peptides, with six of these (AB-1 to AB-6) ranging from 12 to 18 residues
      covering the most hydrophilic regions of the protein, and two more peptides (AB-7
      and AB-8) representing its repetitive sequences. We found that all eight
      constructs bound an appreciable amount of antibody in sera from a large
      proportion of P. falciparum malaria patients; two of these peptides (AB-1 and AB
      3) also elicited a strong proliferation response in peripheral blood mononuclear
      cells from all 11 human subjects recovering from malaria. When used as carrier
      free immunogens, six peptides induced a strong, boostable, immunoglobulin G-type
      antibody response in rabbits, indicating the presence of both B-cell determinants
      and T-helper-cell epitopes in these six constructs. These antibodies specifically
      cross-reacted with the parasite protein(s) in an immunoblot and in an
      immunofluorescence assay. In another immunoblot, rabbit antipeptide sera also
      recognized recombinant fragments of ABRA expressed in bacteria. More
      significantly, rabbit antibodies against two constructs (AB-1 and AB-5) inhibited
      the merozoite reinvasion of human erythrocytes in vitro up to approximately 90%.
      These results favor further studies so as to determine possible inclusion of
      these two constructs in a multicomponent subunit vaccine against asexual blood
      stages of P. falciparum.

PMID- 9596766
TI  - Signal transduction during Legionella pneumophila entry into human monocytes.
AB  - Legionella pneumophila causes Legionnaires' disease by replication in alveolar
      macrophages and monocytes. The bacteria are internalized most efficiently by
      opsonin-dependent, CR3-mediated phagocytosis. This investigation focused on
      determining the role of actin polymerization and phosphorylation signals in this
      uptake mechanism. Uptake inhibition assays and confocal microscopic analysis
      indicated that entry of L. pneumophila activated tyrosine kinase (TK) and protein
      kinase C (PKC) and induced actin polymerization at the site of bacterial entry.
      Upon L. pneumophila entry, six major cellular proteins (75, 71, 59, 56, 53, and
      52 kDa) were TK phosphorylated in soluble fractions of monocytes, and three of
      these proteins (52, 53, and 56 kDa) were consistently found in insoluble (i.e.,
      cytoskeletal) fractions of monocytes as well. Tyrosine phosphorylation was
      suppressed when cells were pretreated with the kinase inhibitor genistein,
      tyrphostin, or staurosporine. A similar tyrosine-phosphorylated protein pattern
      was observed with CR3-mediated entry of avirulent L. pneumophila, Escherichia
      coli, or zymosan into monocytes. This study has shown that PKC and TK signals
      which activate actin polymerization during the process of phagocytosis are
      induced upon L. pneumophila entry. In addition, CR3 receptor-mediated
      phagocytosis into monocytes may involve tyrosine phosphorylation of similar
      proteins, regardless of the particle being phagocytosed. Therefore, the tyrosine
      induced phosphorylation observed during opsonized L. pneumophila entry is not a
      virulence-associated event.

PMID- 9596767
TI  - Haemophilus ducreyi infection causes basal keratinocyte cytotoxicity and elicits
      a unique cytokine induction pattern in an In vitro human skin model.
AB  - Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital
      ulcer disease chancroid. Predominantly a cutaneous pathogen, H. ducreyi is
      present in chancroid ulcers that are characterized by extensive neutrophil
      accumulation in intraepidermal lesions accompanied by a mononuclear infiltrate in
      the dermis. We used an in vitro human skin model composed of foreskin fibroblasts
      and keratinocytes to examine host skin cell interactions with H. ducreyi 35000.
      Bacteria replicated and persisted in artificial skin for at least 14 days. We
      observed H. ducreyi inside suprabasal keratinocytes using transmission electron
      microscopy. Although no bacteria were seen in the basal keratinocyte region,
      these cells were disrupted in infected cocultures. H. ducreyi infection
      stimulated increased secretion of interleukin-6 (IL-6) and IL-8 by skin cells.
      Conversely, tumor necrosis factor alpha and IL-1alpha levels were not elevated.
      IL-8 produced in response to H. ducreyi infection may be involved in recruiting
      polymorphonuclear leukocytes and other inflammatory cells, thereby contributing
      to the tissue necrosis and ulcer formation characteristic of chancroid.

PMID- 9596768
TI  - In vivo binding of immunoglobulin M to the surfaces of Babesia bigemina-infected
      erythrocytes.
AB  - Babesia bigemina infection of mature bovine erythrocytes results in new proteins
      specifically exposed on the parasitized cell surface. Monoclonal antibody (MAb)
      64/32 binds a protein, designated p94, on B. bigemina-infected erythrocytes but
      not on either uninfected or B. bovis-parasitized erythrocytes. However, p94 was
      not encoded by B. bigemina and was not a parasite-modified erythrocyte membrane
      protein. In contrast, we showed that p94 could be eluted from the infected
      erythrocyte surface and was identified as specifically bound immunoglobulin M
      (IgM) heavy chain for the following reasons: (i) MAb 64/32 bound a reduced
      molecule of 94 kDa in both infected erythrocyte lysates and normal bovine serum;
      (ii) MAb 64/32 bound a 94-kDa molecule in reduced preparations of purified IgM;
      (iii) an anti-bovine mu heavy-chain MAb, BIg73, reacted specifically with the
      surface of infected erythrocytes and bound the 94-kDa molecule in lysates of
      infected erythrocytes, normal bovine serum, and purified IgM; and (iv)
      immunoprecipitation of infected erythrocyte lysates with MAb 64/32 depleted the
      94-kDa antigen bound by anti-mu MAb BIg73 and vice versa. Binding of IgM to the
      infected erythrocyte surface was detected in vivo early in acute parasitemia and
      occurred during both the trophozoite and merozoite stages of intraerythrocytic
      parasitism. The common feature of IgM binding to the parasitized erythrocyte
      surface among otherwise genetically and antigenically distinct B. bigemina
      strains is suggestive of an advantageous role in parasite survival in vivo.

PMID- 9596769
TI  - Physical limitations on Salmonella typhi entry into cultured human intestinal
      epithelial cells.
AB  - Kinetic studies of Salmonella typhi invasion of INT407 cells at different
      multiplicities of infection (MOIs) have revealed a strict physical limitation on
      S. typhi entry at MOIs of >/=40. Staining of infected monolayers to distinguish
      intracellular from extracellular bacteria revealed that all monolayer cells are
      susceptible to infection and that internalized bacteria are typically contained
      in one to three separate clusters per cell during the first 60 min. Scanning and
      transmission electron microscopic analyses of time course-infected monolayers
      showed that at early times postinfection, bacteria bind to shortened, coalesced
      microvilli in one to three focal aggregate structures per host cell surface. As
      reported previously for S. typhimurium, focal aggregates progress to conical
      membrane ruffles that appear to engulf one or a few centrally contained S. typhi
      cells by a macropinocytic process, which enhanced the entry of simultaneously
      added Escherichia coli HB101 about 30-fold. Additionally, kinetic studies showed
      that at an MOI of approximately 400, maximal S. typhi entry is virtually
      completed within 30 to 35 min. Monolayers pretreated with S. typhi for 30 min to
      saturate the entry process were severely reduced in the ability to internalize
      subsequently added kanamycin-resistant strains of S. typhi or S. typhimurium, but
      E. coli HB101(pRI203) expressing the cloned Yersinia inv gene was not reduced in
      entry. In invasion inhibition assays, anti-beta1 integrin antibodies markedly
      reduced E. coli HB101(pRI203) invasion efficiency but did not reduce S. typhi
      entry. Collectively, these data provide direct physical and visual evidence which
      indicates that S. typhi organisms are internalized at a limited number (i.e., two
      to four) of sites on host cells. S. typhi and S. typhimurium likely share INT407
      cell entry receptors which do not appear to be members of the beta1 integrin
      superfamily.

PMID- 9596770
TI  - Goldfish, Carassius auratus, a novel animal model for the study of Mycobacterium
      marinum pathogenesis.
AB  - We have developed an animal model for studying mycobacterial pathogenesis using
      Mycobacterium marinum and the goldfish, Carassius auratus. Goldfish are injected
      intraperitoneally with doses between 10(2) and 10(9) CFU of M. marinum organisms.
      Depending on the dose of M. marinum organisms administered, an acute or chronic
      disease is produced. The acute disease is characterized by systemic mycobacterial
      infection, severe peritonitis, tissue necrosis, and a short median survival time.
      The chronic disease is characterized by granuloma formation in all organs and
      survival of animals to the end point of the experiment (56 days). Colony counts
      in organ homogenates showed recovery of mycobacteria from a high percentage of
      inoculated animals. We believe this well-characterized animal model will be
      useful for studying mycobacterial pathogenesis.

PMID- 9596771
TI  - Helicobacter pylori disrupts epithelial barrier function in a process inhibited
      by protein kinase C activators.
AB  - Helicobacter pylori colonizes the gastric mucosa, and the infection is related to
      the development of diverse gastric pathologies, possibly by directly or
      indirectly affecting epithelial-cell function. We analyzed the influence of the
      bacteria on transepithelial electrical resistance (TER) on a model tight
      epithelium, T84, grown to confluence in permeable filters. H. pylori sonicates
      produced a dramatic decrease in TER after 1 to 2 h of exposure, while sonicates
      from other bacteria did not induce a significant reduction of TER. The effect
      induced by sonicates was mimicked by a water-soluble fraction from the bacterial
      surface, was not reproducible with isolated lipopolysaccharide, and was
      concomitant with a significant increase in the paracellular permeability of the
      marker molecule [14C]mannitol. Furthermore, H. pylori sonicates also provoked a
      significant increase in permeability to [14C]mannitol across rat gastric mucosa
      in vitro. The sonicate-induced decrease in TER in T84 monolayers was inhibited by
      the protein kinase C (PKC) activator phorbol myristate acetate. As PKC is
      directly involved in tight junction regulation, we suggest that H. pylori may
      induce intracellular signalling events counteracting PKC effects. Following long
      term H. pylori stimulation, epithelial monolayers regained baseline resistance
      values slowly after 24 h. The resistance recovery process was inhibited by
      cycloheximide, indicating its dependency upon protein synthesis. No association
      between resistance variation and E-cadherin protein levels was observed. These
      results indicate that H. pylori alters in vitro the barrier properties of the
      epithelium, probably by generating cell signalling events counteracting the
      normal function of PKC. This increased permeability may provide a potential
      mechanism by which H. pylori antigens can reach the gastric lamina propria,
      thereby activating the mucosal immune system.

PMID- 9596772
TI  - Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis.
AB  - The results of this study provide the first evidence that two completely separate
      vaccine approaches, one based on a subunit vaccine consisting of a mild adjuvant
      admixed with purified culture filtrate proteins and enhanced by the cytokine
      interleukin-2 and the second based on immunization with DNA encoding the Ag85A
      protein secreted by Mycobacterium tuberculosis, could both prevent the onset of
      caseating disease, which is the hallmark of the guinea pig aerogenic infection
      model. In both cases, however, the survival of vaccinated guinea pigs was shorter
      than that conferred by Mycobacterium bovis BCG, with observed mortality of these
      animals probably due to consolidation of lung tissues by lymphocytic granulomas.
      An additional characteristic of these approaches was that neither induced skin
      test reactivity to commercial tuberculin. These data thus provide optimism that
      development of nonliving vaccines which can generate long-lived immunity
      approaching that conferred by the BCG vaccine is a feasible goal.

PMID- 9596774
TI  - Multiple adhesive phenotypes linked to rosetting binding of erythrocytes in
      Plasmodium falciparum malaria.
AB  - The cerebral form of severe malaria is associated with excessive intravascular
      sequestration of Plasmodium falciparum-infected erythrocytes (PRBC). Retention
      and accumulation of PRBC may lead to occlusion of brain microvessels and direct
      the triggering of acute pathologic changes. Here we report that by selection,
      cloning, and subcloning, we have identified rare P. falciparum parasites
      expressing a pan-adhesive phenotype linked to erythrocyte rosetting, a previously
      identified correlate of cerebral malaria. Rosetting PRBC not only bound
      uninfected erythrocytes but also formed autoagglutinates, adhered to endothelial
      cells, and bound to CD36, immunoglobulins, and the blood group A antigen. The
      linkage of rosetting, autoagglutination, and cytoadherence involved the
      coexpression on a single PRBC of ligands with multiple specificities and the
      binding to two or more receptors on erythrocytes and to at least two other cell
      adhesion molecules, including a new endothelial cell receptor for P. falciparum
      infected erythrocytes. Limited proteolysis that differentially cleaved the
      rosetting ligand PfEMP1 from the PRBC surface abrogated all the binding
      phenotypes of these parasites, implicating the variant antigen PfEMP1 as a
      carrier of multiple ligand specificities. The results encourage the further study
      of pan-adhesion as a potentially important parasite phenotype in the pathogenesis
      of severe P. falciparum malaria.

PMID- 9596773
TI  - Trypanosoma cruzi infection in tumor necrosis factor receptor p55-deficient mice.
AB  - Tumor necrosis factor receptor p55 (TNFRp55) mediates host resistance to several
      pathogens by allowing microbicidal activities of phagocytes. In the studies
      reported here, TNFRp55-/- mice infected with the intracellular parasite
      Trypanosoma cruzi showed clearly higher parasitemia and cumulative mortality than
      wild-type (WT) controls did. However, gamma interferon (IFN-gamma)-activated
      macrophages from TNFRp55-/- mice produced control levels of nitric oxide and
      killed the parasite efficiently in vitro. Trypanocidal mechanisms of
      nonphagocytic cells (myocardial fibroblasts) from both TNFRp55-/- and WT mice
      were also activated by IFN-gamma in a dose-dependent way. However, IFN-gamma
      activated TNFRp55-/- nonphagocytes showed less effective killing of T. cruzi than
      WT control nonphagocytes, even when interleukin 1beta (IL-1beta) was added as a
      costimulator. In vivo, T. cruzi-infected TNFRp55-/- mice and WT mice released
      similar levels of NO and showed similar levels of IFN-gamma mRNA and inducible
      nitric oxide synthase mRNA in their tissues. Instead, increased susceptibility to
      T. cruzi of TNFRp55-/- mice was associated with reduced levels of parasite
      specific immunoglobulin G (IgG) (but not IgM) antibodies during infection, which
      is probably linked to abnormal B-cell differentiation in secondary lymphoid
      tissues of the mutant mice. Surprisingly, T. cruzi-infected TNFRp55-/- mice
      showed increased inflammatory and necrotic lesions in several tissues, especially
      in skeletal muscles, indicating that TNFRp55 plays an important role in
      controlling the inflammatory process. Accordingly, levels of Mn2+ superoxide
      dismutase mRNA, a TNF-induced enzyme which protects the cell from the toxic
      effects of superoxide, were lower in mutant than in WT infected mice.

PMID- 9596775
TI  - LcrG is required for efficient translocation of Yersinia Yop effector proteins
      into eukaryotic cells.
AB  - Extracellular Yersinia disables the immune system of its host by injecting
      effector Yop proteins into host cells. We show that a Yersinia enterocolitica
      nonpolar lcrG mutant is severely impaired in the translocation of YopE, YopH,
      YopM, YpkA/YopO, and YopP into eukaryotic cells. LcrG is thus required for
      efficient internalization of all the known Yop effectors.

PMID- 9596776
TI  - Entamoeba histolytica induces host cell death in amebic liver abscess by a non
      Fas-dependent, non-tumor necrosis factor alpha-dependent pathway of apoptosis.
AB  - Amebic liver abscess is characterized by extensive areas of dead hepatocytes that
      form cavities surrounded by a thin rim of inflammatory cells and few Entamoeba
      histolytica trophozoites. E. histolytica produces pore-forming proteins and
      proteinases, but how trophozoites actually kill host cells has been unclear.
      Here, we report that E. histolytica induces apoptosis in both inflammatory cells
      and hepatocytes in a severe combined immunodeficient (SCID) mouse model of amebic
      liver abscess. By studying infection in C57/BL6.lpr and C57/BL6.gld mice, we
      found that E. histolytica-induced apoptosis does not require the Fas/Fas ligand
      pathway of apoptosis, and by using mice with a targeted deletion of the tumor
      necrosis factor receptor I gene, we have shown that E. histolytica-induced
      apoptosis is not mediated by tumor necrosis factor alpha. Our data indicate that
      apoptosis plays a prominent role in the host cell death seen in amebic liver
      abscess in a mouse model of disease and suggest that E. histolytica induces cell
      death without using two common pathways for apoptosis.

PMID- 9596777
TI  - Extracellular release of antigenic proteins by Helicobacter pylori.
AB  - Screening a Helicobacter pylori genomic library with antisera raised against H.
      pylori broth culture supernatant resulted in the identification of six antigens:
      urease, HspB, Lpp20, DnaK, MsrA, and a cysteine-rich 28-kDa protein (designated
      HcpA). H. pylori antigens may be released into the extracellular space by
      multiple mechanisms, including specific secretion pathways, autolysis, and
      membrane vesicle formation.

PMID- 9596778
TI  - Formation of ring-shaped structures on erythrocyte membranes after treatment with
      botulinolysin, a thiol-activated hemolysin from Clostridium botulinum.
AB  - Damage to erythrocyte membranes by botulinolysin (BLY) was studied by electron
      microscopy, which revealed ring-shaped structures with inner diameters and widths
      of approximately 32 and 6.7 nm, respectively. BLY bound to membranes at 0 degrees
      C, but subsequent treatment with glutaraldehyde prevented ring formation during
      further incubation at 37 degrees C. Zn2+ ions inhibited ring formation but not
      binding of BLY to membranes.

PMID- 9596779
TI  - Acute and chronic phases of Toxoplasma gondii infection in mice modulate the host
      immune responses.
AB  - Murine antibody responses to soluble proteins are generally restricted to the
      immunoglobulin G1 (IgG1) isotype. When mice were infected with Toxoplasma gondii
      Beverley and concomitantly immunized with a soluble unrelated protein antigen, a
      modification in the isotypic distribution of antibodies directed against this
      nonparasite antigen was observed, with a preferential production of IgG2a.
      Interestingly, when mice were immunized with a soluble protein antigen during the
      chronic phase (day 40) of infection with T. gondii Beverley, a similar
      modification in the isotypic distribution of antiprotein antibodies was observed.

PMID- 9596780
TI  - Assimilation of xylose, mannose, and mannitol for synthesis of
      glucuronoxylomannan of Cryptococcus neoformans determined by 13C nuclear magnetic
      resonance spectroscopy.
AB  - Cryptococcus neoformans NIH 409 was cultured in a defined medium containing D-[1
      13C]xylose (Xyl), D-[1-13C]mannose (Man), or D-[1-13C]mannitol as the sole carbon
      source. The distribution of 13C in the Man, Xyl, glucuronic acid (GlcA), and O
      acetyl constituents of native and de-O-acetylated glucuronoxylomannan (GXM) was
      determined by one-dimensional 13C nuclear magnetic resonance spectroscopy. The
      carbon chain of Man was incorporated intact into GXM since 13C was observed only
      in carbon 1 of Man, GlcA, and Xyl. The carbon chain of mannitol was incorporated
      intact into GXM since 13C was observed only in carbons 1 and 6. This was expected
      since mannitol has an axis of symmetry. The carbon chain of Xyl was identified
      only in carbons 1 and 3 of Man, GlcA, and Xyl. This pattern of labeling is
      consistent with the assimilation of Xyl through the pentophosphate pathway.

PMID- 9596781
TI  - Molecular characterization of Treponema pallidum mcp2, a putative chemotaxis
      protein gene.
AB  - The nucleotide sequence of the Treponema pallidum mcp2 gene was determined. mcp2
      encodes a 45.8-kDa protein whose deduced amino acid sequence has significant
      homology with the C-terminal region of bacterial methyl-accepting chemotaxis
      proteins (MCPs). The Mcp2 N terminus lacks the hydrophobic transmembrane regions
      present in most MCPs. An Mcp2 fusion protein was strongly reactive with antibody
      (HC23) to the highly conserved domain of MCPs and with rabbit syphilitic serum.
      Antibody HC23 reacted with six T. pallidum proteins, including a 45-kDa protein
      that may correspond to Mcp2. This protein was present in the aqueous phase from
      T. pallidum cells that were solubilized with Triton X-114 and phase partitioned.

PMID- 9596782
TI  - Secreted aspartyl proteinases and interactions of Candida albicans with human
      endothelial cells.
AB  - The endothelial cell interactions of homozygous null mutants of Candida albicans
      that were deficient in secreted aspartyl proteinase 1 (Sap1), Sap2, or Sap3 were
      investigated. Only Sap2 was found to contribute to the ability of C. albicans to
      damage endothelial cells and stimulate them to express E-selectin. None of the
      Saps studied appears to play a role in C. albicans adherence to endothelial
      cells.

PMID- 9596783
TI  - Human antibody response to Helicobacter pylori lipopolysaccharide: presence of an
      immunodominant epitope in the polysaccharide chain of lipopolysaccharide.
AB  - We have examined the antibody response to Helicobacter pylori lipopolysaccharides
      (LPS) in humans. We used sera from patients with gastroduodenal diseases and
      healthy adults infected or not infected with H. pylori. Data from the experiments
      for antibody binding to LPS suggested that the polysaccharide chains from many H.
      pylori strains showed high immunogenicity in humans. Sera from most (above 70%)
      H. pylori-infected individuals contained immunoglobulin G (IgG) antibodies
      against the polysaccharide region highly immunogenic H. pylori LPS. The IgG
      titers of individual serum samples that reacted strongly with highly immunogenic
      LPS were quite similar (r2 = 0.84 to 0.98). The results suggest wide distribution
      among H. pylori strains of a highly antigenic epitope in the polysaccharide
      moieties of their LPS. Also, the similarity in the titers of individual serum
      samples against highly immunogenic LPS points to the existence of epitopes
      sharing a common structural motif. However, some strains showed low antigenicity,
      even those with polysaccharide-carrying LPS. The dominant subclass of IgG that
      reacted with the highly immunogenic LPS was IgG2, which was preferentially raised
      against polysaccharide antigens. Recently, a structure that mimics that of the
      Lewis antigens was identified in the O-polysaccharide fraction of H. pylori LPS;
      however, no correlation between antigenicity of the polysaccharide chain in
      humans and the presence of Lewis antigens was found. The IgA and IgM titers
      against H. pylori LPS seemed to be mostly nonspecific and directed against lipid
      A. In a few cases, however, sera from individuals infected with H. pylori gave
      strong IgA and IgM titers against the highly immunogenic polysaccharide. In
      conclusion, the LPS of many H. pylori strains possess an antigenic epitope in
      their polysaccharide regions that is immunogenic in humans. However, our results
      show that the antigenic epitope is unlikely to be immunologically related to
      structures mimicking Lewis antigens.

PMID- 9596785
TI  - Identification and molecular analysis of lbpBA, which encodes the two-component
      meningococcal lactoferrin receptor.
AB  - We identified lbpB, encoding the lipoprotein component of the meningococcal
      lactoferrin receptor. An LbpB mutant was unable to acquire Fe from lactoferrin
      and exhibits decreased surface binding to lactoferrin. Primer extension and
      reverse transcription-PCR analysis indicate that lbpB and lbpA are cotranscribed
      on a polycistronic Fe-repressible mRNA.

PMID- 9596784
TI  - Clearance of Shigella flexneri infection occurs through a nitric oxide
      independent mechanism.
AB  - Nitric oxide (NO) generated by gamma interferon (IFN-gamma) activation of
      macrophages mediates the killing of many intracellular pathogens. IFN-gamma is
      essential to innate resistance to Shigella flexneri infection. We demonstrate
      that NO is produced following S. flexneri infection both in mice and in activated
      cells in vitro and that while it is able to kill S. flexneri in a cell-free
      system, it is not required for clearance of S. flexneri in either infected mice
      or in activated cells in vitro.

PMID- 9596786
TI  - Enhanced levels of Staphylococcus aureus stress protein GroEL and DnaK homologs
      early in infection of human epithelial cells.
AB  - Antibodies to Staphylococcus aureus heat shock proteins (Hsps) are present in the
      sera of patients with S. aureus endocarditis (M. W. Qoronfleh, W. Weraarchakul,
      and B. J. Wilkinson, Infect. Immun. 61:1567-1570, 1993). Although these proteins
      are immunogenic, their role in infection has not been established. We developed a
      cell culture system as a model to examine the potential involvement of
      staphylococcal Hsps in the initial events of infection. This study supports a
      model in which a clinical endocarditis isolate responds to host cell signals by
      selectively regulating the synthesis of numerous proteins, including the stress
      proteins Hsp60 (GroEL homolog) and Hsp70 (DnaK homolog) and a unique 58-kDa
      protein.

PMID- 9596787
TI  - Regulation of distal nephron K+ channels (ROMK) mRNA expression by aldosterone in
      rat kidney.
AB  - 1. The expression of ROMK mRNA isoforms in rat kidney was measured using
      competitive polymerase chain reaction. Under basal conditions the expression of
      ROMK2 and 3 mRNA was significantly higher than that of ROMK1 or 6. 2.
      Administration of aldosterone for a period of 1 week significantly increased the
      mRNA expression not only of the alpha1-subunit of the Na+-K+-ATPase, but also of
      ROMK2, 3 and 6. 3. These data not only provide evidence that ROMK K+ channels may
      be involved with mineralocorticoid-sensitive K+ secretion in the distal nephron,
      but also demonstrate for the first time that ROMK6 may be involved in this
      process.

PMID- 9596788
TI  - An analysis of philanthotoxin block for recombinant rat GluR6(Q) glutamate
      receptor channels.
AB  - 1. The action of philanthotoxin 343 (PhTX) on rat homomeric GluR6(Q) recombinant
      glutamate receptor channels was analysed using concentration-jump techniques and
      outside-out patches from HEK 293 cells. Both onset and recovery from block by
      external PhTX were dependent on the presence of agonist, indicating that channels
      must open for PhTX to bind and that channel closure can trap PhTX. 2. Block by
      external PhTX developed with double-exponential kinetics. The rate of onset of
      the fast component of block showed an exponential increase per 27 mV
      hyperpolarization over the range -40 to -100 mV. The rate of onset of the slow
      component of block showed a non-linear concentration dependence indicating a rate
      limiting step in the blocking mechanism. 3. The extent of block by 1 microM
      external PhTX was maximal at -40 mV and did not increase with further
      hyperpolarization; the rate of recovery from block by external PhTX increased 6
      fold on hyperpolarization from -40 to -100 mV suggesting that PhTX permeates at
      negative membrane potentials. 4. Apparent Kd values for block by external PhTX
      estimated from dose-inhibition experiments decreased 300-fold on
      hyperpolarization from +40 mV (Kd, 19.6 microM) to -40 mV (Kd, 69 nM); there was
      little further increase in affinity with hyperpolarization to -80 mV (Kd, 56 nM),
      consistent with permeation of PhTX at negative membrane potentials. 5. Block by
      internal PhTX showed complex kinetics and voltage dependence. Analysis with
      voltage ramps from -120 to +120 mV indicated a Kd at 0 mV of 20 microM,
      decreasing e-fold per 16 mV depolarization. However, at +90 mV the extent of
      block by 1 and 10 microM internal PhTX (73 % and 95 %, respectively) reached a
      maximum and did not increase with further depolarization. 6. Voltage-jump
      analysis of block by 100 microM internal PhTX revealed partial trapping. With 100
      ms jumps from -100 to -40 mV, onset and recovery from block were complete within
      5 ms. With jumps of longer duration the extent of block increased, with a time
      constant of 8.1 s, reaching 84 % at 30 s. On repolarization to -100 mV, recovery
      from block showed fast and slow components. 7. The amplitude of the slow
      component of block by internal PhTX showed a biphasic voltage dependence, first
      increasing then decreasing with progressive depolarization. Maximum block was
      obtained at 0 mV. 8. Our results suggest that PhTX acts as an open channel
      blocker; however, provided that the toxin remains bound to the channel, an
      allosteric mechanism destabilizes the open state, inducing channel closing and
      trapping PhTX. Strong depolarization for internal PhTX, or strong
      hyperpolarization for external PhTX, forces the toxin to permeate before it
      triggers entry into closed blocked states.

PMID- 9596789
TI  - Functional contribution of the alpha7 subunit to multiple subtypes of nicotinic
      receptors in embryonic chick sympathetic neurones.
AB  - 1. Many studies of the alpha7 subunit of the neuronal nicotinic acetylcholine
      receptor (nAChR) family have demonstrated that this alpha-bungarotoxin (alpha
      BgTx)-binding neuronal receptor can participate in ACh-gated channels.
      Heterologous expression studies reveal that alpha7 subunits form homomeric
      channels of unusually high Ca2+ permeability. However, the physiological role of
      the alpha7 subunit in native neuronal nAChR channels is less clear. 2. We present
      evidence that the alpha7 subunit contributes to the function of at least three
      subtypes of native nAChR expressed by embryonic chick sympathetic neurones. These
      subtypes are functionally distinct from heterologously expressed homomeric alpha7
      nAChRs as well as homomeric-like currents described in studies of hippocampal and
      parasympathetic neurones. 3. The proposed nAChRs differ from one another and from
      homomeric alpha7 nAChRs in their sensitivity to block by alpha7 subunit-specific
      antagonists: alpha-BgTx and methyllycaconitine (MLA). While MLA blocks 60 % of
      the macroscopic ACh response, alpha-BgTx inhibits a small component of the
      macroscopic current described by slow-on and slow-off kinetics. 4. Functional
      deletion of the alpha7 subunit by antisense oligonucleotide treatment eliminates
      the susceptibility of the nAChRs to block by both MLA and alpha-BgTx. 5. Single
      channel recordings combined with pharmacological and antisense-mediated
      'deletion' techniques reveal that alpha-BgTx-sensitive alpha7-containing nAChRs
      have a small unitary conductance (18 pS), brief open time kinetics and relatively
      low open probability (Po). MLA-sensitive alpha7 nAChRs are characterized by a
      conductance of approximately 35 pS, intermediate burst duration, and a relatively
      high Po. 6. The third nAChR subtype deleted by alpha7 antisense treatment is
      characterized by a unitary conductance of 50 pS and prolonged opening duration.
      7. We propose that these three populations of native alpha7-containing nAChRs are
      distinct heteromeric complexes that include other alpha and/or beta nAChR
      subunits.

PMID- 9596790
TI  - Functional contribution of the alpha5 subunit to neuronal nicotinic channels
      expressed by chick sympathetic ganglion neurones.
AB  - 1. Heterologous expression studies of the alpha5 subunit of the neuronal
      acetylcholine receptor (nAChR) gene family have demonstrated that it can
      participate in the function of ACh-gated channels if co-expressed with another
      alpha- and a beta-subunit. Previous studies also indicate prominent expression of
      alpha5 in both central and peripheral nervous systems. The participation of
      alpha5 in native nAChRs and its functional role in these channels is, however,
      unknown. 2. In this study, we present evidence that alpha5 has a role in at least
      two distinct subtypes of nAChR complexes expressed by embryonic chick sympathetic
      neurones. 3. alpha5 contributes not only to agonist but also to antagonist
      sensitivity of natively expressed nAChR channels. Functional deletion of the
      alpha5 subunit by antisense oligonucleotide treatment removes the nAChRs with
      relatively low affinity to ACh and cytisine. Deletion of alpha5 also eliminates
      channels that are blocked by the alpha7-specific antagonist methyllycaconitine
      (MLA) while increasing the percentage of current carried by nAChRs that are
      sensitive to alpha-bungarotoxin (alpha-BgTx). 4. Single channel analyses indicate
      that functional deletion of alpha5 results in the deletion of both the 'brief'
      and 'long' open duration, 50 pS subtypes of nAChR channels while increasing the
      expression of the 18 pS, alpha-BgTx-sensitive native nAChRs normally detected in
      sympathetic neurones at later developmental stages. 5. The biophysical and
      pharmacological profiles of native nAChRs revealed by this study and previous
      work are discussed in the context of a proposed model of the nAChR channels
      expressed by chick sympathetic neurones throughout development.

PMID- 9596791
TI  - Presynaptic 5-HT3 receptors evoke an excitatory response in dorsal vagal
      preganglionic neurones in anaesthetized rats.
AB  - 1. Recordings were made from a total of sixty-four vagal preganglionic neurones
      in the dorsal vagal motor nucleus (DVMN) of pentobarbitone sodium anaesthetized
      rats. The effects of ionophoretic administration of Mg2+ and Cd2+, inhibitors of
      neurotransmitter release, and the selective NMDA and non-NMDA receptor
      antagonists (+/-)-2-amino-5-phosphono-pentanoic acid (AP5) and 6,7
      dinitroquinoxaline-2,3-dione (DNQX) on the excitatory actions of the 5-HT3
      receptor agonist 1-phenylbiguanide (PBG) were studied. 2. In extracellular
      recording experiments, PBG (0-40 nA) increased the firing rate of thirty-five of
      the thirty-nine neurones tested. The PBG-evoked excitation was attenuated by
      application of Mg2+ (1-10 nA) in sixteen of seventeen neurones or Cd2+ (2-10 nA)
      in seven of eight neurones tested. At these low ejection currents neither Mg2+
      nor Cd2+ altered baseline firing rates and Mg2+ had no effect on the excitations
      evoked by DL-homocysteic acid (n = 4), NMDA (n = 4) or (AMPA; n = 2). 3.
      Ionophoresis of AP5 (2-10 nA), at currents which selectively inhibited NMDA
      evoked excitations, attenuated PBG-evoked excitations in all eight neurones
      tested. DNQX (5-20 nA), at currents which selectively inhibited AMPA-evoked
      excitations, also attenuated PBG-evoked excitations (n = 3). 4. Intracellular
      activity was recorded in nine DVMN neurones. In six neurones ionophoretic
      application of PBG (10-200 nA) depolarized the membrane and increased firing rate
      whilst in the other three neurones, PBG had no effect on membrane potential
      though it increased synaptic noise (n = 3) and firing rate (n = 2). In all six
      neurones tested, ionophoresis of Mg2+ (10-120 nA) attenuated the PBG-evoked
      increases in synaptic noise and firing rate. 5. In conclusion, the data are
      consistent with the hypothesis that 5-HT3 receptor agonists activate DVMN
      neurones partly by acting on receptors located at sites presynaptic to the
      neurones. Activation of these receptors appears to facilitate release of
      glutamate, which, in turn, acts on postsynaptic NMDA and non-NMDA receptors to
      activate the neurones.

PMID- 9596792
TI  - Effect of depletion of interstitial hyaluronan on hydraulic conductance in rabbit
      knee synovium.
AB  - 1. The hydraulic resistance of the synovial lining to fluid outflow from a joint
      cavity (Qs) is important for the retention of intra-articular lubricant. The
      resistance has been attributed in part to extracellular glycosaminoglycans,
      including hyaluronan and chondroitin sulphates. Increased permeability in joints
      infused with testicular hyaluronidase, which digests both chondroitin sulphates
      and hyaluronan, supports this view. In this study the importance of interstitial
      hyaluronan per se was assessed using leech and Streptomyces hyaluronidases, which
      degrade only hyaluronan. 2. Ringer solution was infused into the knee joint
      cavity of anaesthetized rabbits for 30 min, with or without hyaluronidase, after
      which intra-articular pressure (Pj) was raised and the relation between pressure
      and outflow determined. 3. Treatment with Streptomyces, leech or testicular
      hyaluronidases increased the fluid escape rates by similar factors, namely 4- to
      6-fold. After Streptomyces hyaluronidase treatment the slope d 8d s/dPj, which at
      low pressures represents synovial hydraulic conductance, increased from a control
      of 0.90 +/- 0.20 microl min-1 cmH2O-1 (mean +/- s.e.m. , n = 6) to 4.52 +/- 0.70
      microl min-1 cmH2O-1. The slope d 8d s/dPj increased to a similar level after
      testicular hyaluronidase, namely to 4.14 +/- 1.06 microl min-1 cmH2O-1 (control,
      0.54 +/- 0.24 microl min-1 cmH2O-1). Streptomyces and leech hyaluronidases were
      as effective as testicular hyaluronidase (no statistically significant
      differences) despite differences in substrate specificity. 4. It was shown using
      histochemical and immunohistochemical techniques that hyaluronan was removed from
      the synovium by leech, Streptomyces and testicular hyaluronidases. The binding of
      antibodies 2-B-6 and 3-B-3 showed that the core proteins of the chondroitin
      sulphate proteoglycans remained intact after treatment with hyaluronidases, and
      the binding of 5-D-4 showed that keratan sulphate was unaffected. An azocasein
      digestion assay confirmed that the hyaluronidase preparations had no significant
      proteolytic activity. 5. The effect of the hyaluronidases was four times greater
      than predicted from the low concentration of interstitial hyaluronan and its
      resistivity. Factors that might amplify the effect of hyaluronan depletion
      include the matrix-organizing role of hyaluronan, and/or non-uniformity of
      hyaluronan distribution. It is concluded that interstitial hyaluronan makes a
      major contribution to synovial hydraulic resistance, but the mechanisms are as
      yet poorly understood.

PMID- 9596793
TI  - Albumin elicits calcium signals from astrocytes in brain slices from neonatal rat
      cortex.
AB  - 1. Albumin causes calcium signals and mitosis in cultured astrocytes, but it has
      not been established whether astrocytes in intact brain also respond to albumin.
      The effect of albumin on intracellular calcium concentration ([Ca2+]i) in single
      cells was therefore studied in acutely isolated cortical brain slices from the
      neonatal rat. 2. Physiological concentrations of albumin from plasma and from
      serum produced an increase in [Ca2+]i in a subpopulation of cortical cells.
      Trains of transient elevations in [Ca2+]i (Ca2+ spikes) were seen in 41 % of
      these cells. 3. The cells responding to albumin are identified as astrocytes
      because the neurone-specific agonist NMDA caused much smaller and slower
      responses in these cells. On the other hand NMDA-responsive cells, which are
      probably neurones, exhibited only small and slow responses to albumin. The
      residual responses of astrocytes to NMDA and neurones to albumin are likely to be
      due to crosstalk with adjacent neurones and astrocytes, respectively. 4. Methanol
      extraction of albumin removes a polar lipid and abolishes the ability of albumin
      to increase intracellular calcium. 5. Astrocyte calcium signalling caused by
      albumin may have important physiological consequences when the blood-brain
      barrier breaks down and allows albumin to enter the CNS.

PMID- 9596794
TI  - Sensitivity to 5-hydroxytryptamine in different afferent subpopulations within
      mesenteric nerves supplying the rat jejunum.
AB  - 1. This study was performed to elucidate the type of afferents that mediate the
      multiple actions of 5-hydroxytryptamine (5-HT) on mesenteric nerve discharge.
      Electrophysiological recordings were made from mesenteric afferents innervating
      the mid-jejunum of the urethane-anaesthetized rat. The discharge of single nerves
      within the whole nerve recording was monitored using waveform discrimination
      software. 2. Afferents responded to 5-HT in one of two ways: a short latency,
      transient excitation mediated by 5-HT3 receptors, or a delayed onset, more
      prolonged effect that was 5-HT2A receptor mediated. Afferents showing the 5-HT3
      mediated response did not respond to luminal distension but were sensitive to
      intraluminal hydrochloric acid (150 mM) in twenty-eight of twenty-nine
      experiments. In eight experiments, the 5-HT3-mediated response was reversibly
      abolished by a 2 min exposure to intraluminal application of local anaesthetic (2
      % Xylocaine). 3. Mechanosensitive afferents which responded to distension (< 10
      cmH2O) did not show a 5-HT3-mediated response (P = 0.92, n = 14), and maintained
      this mechanosensitivity after luminal anaesthesia. Mechanosensitive afferents did
      show a secondary response to 5-HT that was significantly attenuated by atropine
      (100-200 microg kg-1), whereas hexamethonium (8 mg kg-1) had no effect. 4. In
      animals whose vagal afferent contribution to their mesenteric nerves had been
      eliminated by chronic truncal vagotomy, the 5-HT3-mediated response was absent in
      thirty-six of thirty-six nerve bundles. In contrast, mechanosensitivity to
      distension and the secondary response to 5-HT could still be evoked. 5. These
      results suggest that 5-HT stimulates mesenteric afferents by a direct action on 5
      HT3 receptors that are present on vagal mucosal afferent terminals. The mucosal
      afferent response to luminal acid, however, was unaffected by treatment with
      granisetron (0.5 mg kg-1) indicating that endogenous 5-HT from enterochromaffin
      cells is not essential for transduction of this luminal signal. In contrast,
      mechanosensitivity in non-vagal afferents was modulated by 5-HT following an
      intestinal motor response which was influenced by cholinergic tone.

PMID- 9596795
TI  - Role of 5-HT3 receptors in activation of abdominal sympathetic C fibre afferents
      during ischaemia in cats.
AB  - 1. Activation of abdominal sympathetic afferents during ischaemia reflexly
      excites the cardiovascular system. We have shown previously that exogenous 5
      hydroxytryptamine (5-HT, i.e. serotonin) stimulates abdominal sympathetic
      afferent nerve endings, and recently have documented increased concentrations of
      5-HT in intestinal lymph and portal venous plasma during brief abdominal
      ischaemia. The present investigation evaluated the role of endogenously produced
      5-HT in activation of ischaemically sensitive abdominal sympathetic afferents. 2.
      Nerve activity of single-unit C fibre afferents innervating duodenum, mesentery,
      pancreas, portal hepatis, bile duct, gall bladder and jejunum was recorded from
      the right thoracic sympathetic chain of anaesthetized cats. Ischaemically
      sensitive C fibre afferents were identified according to their response to 5-10
      min of abdominal ischaemia. 3. Intra-arterial injection of 5-HT (20 microg kg-1)
      increased discharge activity of twelve afferents from 0. 23 +/- 0.05 to 0.96 +/-
      0.09 impulses s-1 after an onset latency of 5.7 +/- 1.4 s. Also, 2
      methylserotonin (100 microg kg-1, i.a.), a 5-HT3 receptor agonist, stimulated
      eleven of twelve afferents to significantly increase their discharge activity
      from 0.25 +/- 0.05 to 0.90 +/- 0.10 impulses s-1 after a latency of 3.3 +/- 0.4
      s. Furthermore, intravenous injection of tropisetron (200 microg kg-1), a 5-HT3
      receptor antagonist, significantly attenuated the increase in activity of twelve
      other C fibre afferents during 10 min of abdominal ischaemia from 1.62 +/- 0.18
      to 0.94 +/- 0.22 impulses s-1, and eliminated the response of eleven other
      afferents to 5-HT. 4. Both the 5-HT2 receptor agonist, alpha-methylserotonin (100
      microg kg-1, i.a.), and the 5-HT1 receptor agonist, 5-carboxamidotryptamine (100
      microg kg-1, i.a.), did not alter the impulse activity of these twelve afferents
      (0.29 +/- 0.05 to 0.31 +/- 0.06, and 0.26 +/- 0.06 to 0.29 +/- 0.06 impulses s-1,
      respectively). 5. Treatment with indomethacin (5 mg kg-1, i.v.) in eight
      different cats did not alter the response of nine C fibre afferents to exogenous
      5-HT (0.91 +/- 0. 17 vs. 1.19 +/- 0.25 impulses s-1, P > 0.05). 6. The results
      suggest that, during mesenteric ischaemia, endogenous 5-HT contributes to the
      activation of abdominal sympathetic afferents, mainly through direct stimulation
      of 5-HT3 receptors and that the action of 5-HT on these afferents appears to be
      independent of the cyclo-oxygenase pathway.

PMID- 9596796
TI  - Characteristics of nitric oxide-mediated cholinergic modulation of calcium
      current in rabbit sino-atrial node.
AB  - 1. We have previously shown that nitric oxide (NO) production is essential for
      cholinergic inhibition of the beta-adrenergic stimulated L-type calcium current
      (ICa-L) in rabbit pacemaker (sino-atrial node (SAN)) cells. The present
      experiments demonstrate the presence of constitutive nitric oxide synthase (cNOS)
      in SAN cells, and characterize the NO-mediated cholinergic response. 2.
      Immunohistochemical staining, using an antibody prepared against endothelial
      cNOS, demonstrated that this enzyme was present in single myocytes obtained from
      the SAN. 3. The activation of cNOS is known to be Ca2+ and calmodulin dependent.
      Strongly buffering intracellular Ca2+ with the membrane-permeable chelator BAPTA
      AM (10 microM) significantly reduced (and in some cases abolished) the
      attenuation of ICa-L by the muscarinic agonist carbamylcholine (CCh). In
      contrast, the CCh-induced activation of an outward K+ current, IK,ACh, was
      unaffected by buffering of [Ca2+]i. The calmodulin inhibitor 48/80 (20 microM)
      also abolished the attenuation of ICa-L by CCh, with no change in the activation
      of IK,ACh. 4. Neither thapsigargin nor ryanodine (5-10 microM), agents which
      deplete intracellular Ca2+ stores, significantly changed the attenuation of ICa-L
      by CCh. 5. Pertussis toxin (PTX) completely abolished both the inhibitory action
      of CCh on ICa-L and the activation of IK,ACh. This establishes that a PTX
      sensitive GTP-binding protein links the muscarinic receptor to NO synthase
      activation in SAN cells. 6. Our hypothesis is that NO leads to activation of a
      cyclic GMP (cGMP)-activated phosphodiesterase (PDE II) as a mechanism for
      enhanced cyclic AMP breakdown and ICa-L attenuation. This was supported by
      showing that a specific inhibitor of PDE II, erythro-9-(2-hydroxy-3-nonyl)
      adenine (EHNA), blocks the effect of CCh on ICa-L, but not on IK,ACh. Using
      reverse transcriptase-polymerase chain reaction techniques, we have established
      that PDE II is the dominant cyclic nucleotide phosphodiesterase isoform in SAN
      cells.

PMID- 9596797
TI  - Hypoxia activates ATP-dependent potassium channels in inspiratory neurones of
      neonatal mice.
AB  - 1. The respiratory centre of neonatal mice (4 to 12 days old) was isolated in 700
      micro(m) thick brainstem slices. Whole-cell K+ currents and single ATP-dependent
      potassium (KATP) channels were analysed in inspiratory neurones. 2. In cell
      attached patches, KATP channels had a conductance of 75 pS and showed inward
      rectification. Their gating was voltage dependent and channel activity decreased
      with membrane hyperpolarization. Using Ca2+-containing pipette solutions the
      measured conductance was lower (50 pS at 1.5 mM Ca2+), indicating tonic
      inhibition by extracellular Ca2+. 3. KATP channel activity was reversibly
      potentiated during hypoxia. Maximal effects were attained 3-4 min after oxygen
      removal from the bath. Hypoxic potentiation of open probability was due to an
      increase in channel open times and a decrease in channel closed times. 4. In
      inside-out patches and symmetrical K+ concentrations, channel currents reversed
      at about 0 mV. Channel activity was blocked by ATP (300-600 microM),
      glibenclamide (10-70 microM) and tolbutamide (100-300 microM). 5. In the presence
      of diazoxide (10-60 microM), the activity of KATP channels was increased both in
      inside-out, outside-out and cell-attached patches. In outside-out patches, that
      remained within the slice after excision, the activity of KATP channels was
      enhanced by hypoxia, an effect that could be mediated by a release of endogenous
      neuromodulators. 6. The whole-cell K+ current (IK) was inactivated at negative
      membrane potentials, which resembled the voltage dependence of KATP channel
      gating. After 3-4 min of hypoxia, K+ currents at both hyperpolarizing and
      depolarizing membrane potentials increased. IK was partially blocked by
      tolbutamide (100-300 microM) and in its presence, hypoxic potentiation of IK was
      abolished. 7. We conclude that KATP channels are involved in the hypoxic
      depression of medullary respiratory activity.

PMID- 9596798
TI  - Uneven distribution of K+ channels in soma, axon and dendrites of rat spinal
      neurones: functional role of the soma in generation of action potentials.
AB  - 1. A novel method of 'entire soma isolation' was used to describe the
      distribution of voltage-gated K+ channels between soma, axon and dendrites of
      dorsal horn neurones identified in spinal cord slices of newborn rat. 2. The soma
      contained 36 % of total inactivating (KA) current but only 15 % of delayed
      rectifier (KDR) current. The axon initial segment possessed almost half (47 %) of
      the total KA current and 38 % of KDR current. In contrast, dendrites contained a
      small portion (17 %) of KA but 47 % of KDR current. 3. Under current-clamp
      conditions, the soma isolated from axon and dendrites was not able to generate
      action potentials. It passively conducted weak (</= -50 mV) and amplified
      pronounced (-50 to 0 mV) depolarizations but inhibited strong (>/= 0 mV)
      depolarizations. 4. It is concluded that the soma plays a complex role in the
      excitability of spinal dorsal horn neurones. It conducts passively or amplifies
      excitatory postsynaptic potentials on their way from dendrites and soma to the
      axon initial segment but it inhibits back-propagation of the action potential
      from the axon to the dendrites.

PMID- 9596799
TI  - Autaptic inhibitory currents recorded from interneurones in rat cerebellar
      slices.
AB  - 1. While the presence of autapses in the brain is indicated by a large body of
      morphological evidence, the functional role of these structures has remained
      unclear. To probe for autaptic currents, we have recorded current responses
      following short somatic depolarizing pulses in Cl--loaded interneurones (stellate
      and basket cells) from rat cerebellar slices (animals aged 27-39 days). 2. In
      approximately 20 % of the recordings, fluctuating inward current transients were
      obtained with a latency of 1.15-2.45 ms (measured from the peak of the
      depolarization-induced Na+ current; n = 10). 3. These transients were blocked by
      bicuculline and were sensitive to the extracellular Ca2+ concentration. 4.
      Assuming low release probability, as suggested by the high failure rate (0.65
      0.92, n = 10), quantal sizes ranging from 21 to 178 pA (-70 mV; n = 10) were
      calculated from a variance analysis of autaptic current amplitudes. 5. We
      conclude that approximately 20 % of interneurones have a functional autapse.
      Autaptic currents may inhibit firing of interneurones during high frequency
      discharges.

PMID- 9596800
TI  - Laminar organization of epileptiform discharges in the rat entorhinal cortex in
      vitro.
AB  - 1. Interictal and ictal epileptiform discharges induced by 4-aminopyridine (4AP,
      50 microM) were studied in the rat lateral entorhinal cortex with field potential
      and intracellular recordings in an in vitro slice preparation. Both types of
      discharge disappeared in layer II, but continued to occur in layers IV-VI after a
      knife cut separation was made at approximately 600 micro(m) from the pia (n = 4
      slices). 2. Interictal depolarizations recorded in layer IV-VI cells (amplitude,
      29.4 +/- 8.6 mV; duration, 386 +/- 177.4 ms, means +/- s.d.; n = 17) were capped
      by action potential bursts, while smaller interictal depolarizations in layer II
      cells (amplitude, 11.7 +/- 5.8 mV; duration, 192.6 +/- 47.9 ms; n = 10) were
      associated with single action potentials and were terminated by a
      hyperpolarization. Ictal discharges were initiated by an interictal discharge;
      they were characterized by a depolarization of 31.5 +/- 6.2 mV (n = 12) in layer
      IV-VI and 11.6 +/- 3.5 mV (n = 7) in layer II neurones. 3. Slow, presumptive Ca2+
      mediated spikes occurred in layer II (n = 4) and IV-VI (n = 6) cells loaded with
      the Na+ channel blocker QX-314 (50 mM). These events were synchronized with
      population spikes during interictal and ictal discharges, and were abolished by
      Ni2+ (1 mM, n = 4 cells) along with the 4AP-induced synchronous activity. 4. The
      N-methyl-D-aspartate (NMDA) receptor antagonist 3, 3-(2-carboxypiperazine-4-yl)
      propyl-1-phosphonate (CPP, 10 microM) abolished ictal discharges and reduced
      interictal depolarizations in layer IV-VI neurones (n = 4). The non-NMDA receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) abolished both
      interictal and ictal activity (n = 4 cells). 5. These findings provide evidence
      for a role played by NMDA-mediated mechanisms in the generation of epileptiform
      discharges in the entorhinal cortex. Lack of an NMDA-mediated component along
      with presence of inhibition in layer II neurones results in attenuation of
      epileptiform activity at this site. Moreover Ca2+-mediated spikes may contribute
      to the appearance of epileptiform discharges in this model.

PMID- 9596801
TI  - The influence of corticofugal feedback on the temporal structure of visual
      responses of cat thalamic relay cells.
AB  - 1. Visually driven single-unit activity was recorded in the dorsal lateral
      geniculate nucleus (dLGN) of the anaesthetized cat while inactivating or
      stimulating the corticofugal feedback from area 17/18 by means of cortical
      cooling or application of GABA (inactivation), or application of glutamate or
      quisqualate (Glu, Quis; stimulation) to layer VI. 2. Manipulations of the
      corticofugal feedback primarily affected the multimodal interspike interval
      pattern previously reported to be present in the tonic component of visual
      responses elicited by spot-like stimuli. 3. Sixty-three per cent of all neurons
      could be influenced, and temporally localized interspike interval distributions
      were measured which commonly consisted of one fundamental interval peak (leftmost
      peak) and integer multiples thereof (higher order peaks). During blockade of the
      corticofugal feedback, interspike intervals were redistributed into the higher
      order peaks in about 70 % of the cases, accompanied by a reduced mean firing
      rate. During stimulation the reverse effect occurred in 69 % of cases. 4.
      Increased synchronization of the EEG (increased power in the delta-wave range, 1
      4 Hz) had an effect similar to cortex inactivation. The specificity of
      corticofugal effects was verified by consideration of these EEG effects and by
      dLGN double recordings with one dLGN cell topographically matched with the
      cortical inactivation/activation site and the second cell outside this area.
      Clear effects due to manipulation of the corticofugal feedback were found only
      for the matched dLGN site. 5. In addition we observed that the peaks of the
      interval distributions were narrower during active corticofugal feedback, such
      that the temporal dispersion of the signal transmission to the cortex was
      reduced. 6. The mechanisms underlying this effect were further analysed in a
      biophysically realistic model demonstrating that the timing of the spikes in the
      dLGN is improved as soon as the cortical feedback is active. The high degree of
      convergence/divergence between neurons along the closed feedback loop thereby
      leads to a temporal averaging effect which reduces the interval dispersion and
      also introduces synchronization between dLGN cells. 7. Such a mechanism may thus
      counteract the deterioration of spike timing accuracy which would otherwise occur
      as a consequence of synaptic noise and other uncorrelated sources of activity at
      a given neuron.

PMID- 9596802
TI  - Potentiation of GABAergic synaptic transmission by AMPA receptors in mouse
      cerebellar stellate cells: changes during development.
AB  - 1. The effects of low concentrations of domoate, an agonist at both alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate and kainate receptors (AMPARs and KARs,
      respectively), were investigated in stellate cells in slices of mouse cerebellum
      at two developmental stages (postnatal day (PN) 11-13 and PN21-25). 2. Low
      concentrations of domoate enhanced the frequency of miniature IPSCs (mIPSCs)
      recorded in the presence of tetrodotoxin (TTX) at PN11-13 but not at PN21-25. 3.
      The effects of low concentrations of domoate on synaptic activity were probably
      mediated by the activation of AMPARs and not KARs, since they were blocked by
      GYKI 53655 (LY300168), a selective AMPAR antagonist. 4. Domoate increased mIPSC
      frequency in part by activation of presynaptic voltage-dependent Ca2+ channels
      since potentiation was reduced by 60 % in the presence of Cd2+. AMPARs in
      stellate cells were found to be permeable to Ca2+. The residual potentiation in
      the presence of Cd2+ could thus be due to a direct entry of Ca2+ through AMPAR
      channels. 5. In the presence of TTX, potentiation of synaptic activity by focal
      application of domoate was not restricted to the region of the cell body, but was
      observed within distances of 120 micro(m). These experiments also revealed a
      strong spatial correlation between the location of the presynaptic effects of
      domoate and the activation of postsynaptic AMPARs. 6. Our data show a
      developmentally regulated presynaptic potentiation of synaptic transmission
      between cerebellar interneurones mediated by AMPARs. We discuss the possibility
      that the developmental switch could be due to a shift in the localization of
      AMPARs from the axonal to the somato-dendritic compartment.

PMID- 9596803
TI  - Kainate receptor-mediated inhibition of presynaptic Ca2+ influx and EPSP in area
      CA1 of the rat hippocampus.
AB  - 1. The effect of a low concentration (1 microM) of kainate (kainic acid; KA) on
      presynaptic calcium (Ca2+) influx at the Schaffer collateral-commissural (SCC)
      synapse was examined in rat hippocampal slices. 2. Following selective loading of
      the presynaptic terminals with the fluorescent Ca2+ indicator rhod-2 AM,
      transient increases in the presynaptic Ca2+ concentration (pre[Ca2+]t) and field
      excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of
      the SCC pathway were recorded simultaneously. 3. Bath application of 1 microM KA
      reversibly suppressed field EPSPs and pre[Ca2+]t to 37.7 +/- 4.0 % and 72.9 +/-
      2.4 % of control, respectively. Excitatory postsynaptic currents (EPSCs) recorded
      with the use of the whole-cell patch-clamp technique were also suppressed by 1
      microM KA to 42.6 +/- 6.3 % of control. A quantitative analysis of the decreases
      in pre[Ca2+]t and the amplitude of field EPSP during KA application suggests that
      KA inhibits transmission primarily by reducing the pre[Ca2+]t. 4. Consistent with
      a presynaptic site for these effects, paired-pulse facilitation (PPF) was
      enhanced by 1 microM KA. 5. A substantial KA-induced suppression of NMDA receptor
      mediated EPSPs was detected when AMPA receptors were blocked by the AMPA receptor
      selective antagonist GYKI 52466 (100 microM). 6. The suppressive effect of KA on
      field EPSPs and pre[Ca2+]t was antagonized by the KA antagonist NS-102 (10
      microM). 7. These results suggest that the presynaptic inhibitory action of KA at
      the hippocampal CA1 synapse is primarily due to the inhibition of Ca2+ influx
      into the presynaptic terminals.

PMID- 9596805
TI  - Postnatal changes in responses of rat dorsal horn cells to afferent stimulation:
      a fibre-induced sensitization.
AB  - 1. In vivo extracellular recordings were made of 171 dorsal horn cells in both
      superficial and deep laminae in urethane-anaesthetized newborn rats aged 3, 6, 10
      and 21 days, and their response to single and repeated stimuli to primary
      afferent fibres investigated. 2. No long-latency spike responses were evoked in
      response to C fibre stimulation in pups at postnatal day 3 (P3) or P6, while by
      P10, 35 % of cells had a C fibre response. Latencies of response to A fibre skin
      stimulation were very long and varied widely in the youngest animals,
      particularly in superficial cells, but mean latencies decreased with postnatal
      age, from 33.1 +/- 2.78 ms at P3 to 7.3 +/- 0.3 ms at P21. The mean number of
      spikes evoked by a single A fibre skin stimulus was remarkably consistent between
      cells and not significantly different in superficial and deep laminae at each
      age. The mean value of 5.1 +/- 0.6 at P3 increased to 7.0 +/- 1.4 at P10. 3.
      Repeated stimulation of cutaneous A fibres at 0.5 Hz at twice the threshold level
      did not significantly alter the magnitude of the evoked response but led to
      shifts in latency, or 'latency jitter', which decreased with age. Deeper cells
      displayed more latency jitter than superficial cells. 4. Repeated stimulation of
      cutaneous A fibres at 0.5 Hz at twice the threshold level produced considerable
      sensitization in a population of dorsal horn cells in the neonate. This
      sensitization was unlike the classic C fibre-evoked 'wind-up' observed in adult
      dorsal horn. The direct A fibre-evoked activity did not increase, but the
      background activity increased during repetitive stimulation leading to a
      prolonged after-discharge beyond the stimulation period. At P6, 33 % of cells
      were sensitized, displaying a mean after-discharge of 70.6 +/- 18 s. At P10, only
      6 % were sensitized, with a mean after-discharge of 63 s, and by P21,
      sensitization was no longer observed. 5. The present study demonstrates that the
      postsynaptic activity evoked in neonatal dorsal horn cells by cutaneous afferents
      differs considerably from that in adults. The results may account for the known
      behavioural reflex sensitization to low-intensity cutaneous stimulation observed
      in neonatal rats and man.

PMID- 9596804
TI  - Astrocytes regulate developmental changes in the chloride ion gradient of
      embryonic rat ventral spinal cord neurons in culture.
AB  - 1. Embryonic rat ventral spinal cord neurons were dissociated at day 15 and grown
      on: (i) poly-D-lysine (PDL); (ii) a confluent monolayer of type I astrocytes; or
      (iii) PDL in astrocyte-conditioned medium (ACM) to examine the influence of
      astroglia on the regulation of GABAA receptor/Cl- channel properties. 2.
      Potentiometric oxonol dye recordings of intact cells indicated that embryonic
      neurons were uniformly depolarized by muscimol. The depolarizing effects
      disappeared in cells dissociated during the early postnatal period and recovered
      in culture for 24 h. Similar recordings using the calcium-imaging dye fura-2 AM
      revealed that GABA or muscimol triggered a sustained rise in cytosolic Ca2+
      (Ca2+c ) in embryonic neurons that was dependent on extracellular Ca2+, blocked
      by bicuculline and nifedipine and sensitive to changes in extracellular chloride.
      The incidence and amplitude of the Ca2+ response decreased with time in vitro and
      was accelerated in neurons cultured on astrocytes compared with those on PDL. 3.
      Perforated patch-clamp recordings revealed that GABA depolarized neurons in a Cl-
      dependent and bicuculline-sensitive manner. Both the resting membrane potential
      and the GABA equilibrium potential became more hyperpolarized with time in vitro.
      4. Astrocytes and ACM accelerated the transformation of GABAergic potential
      responses from depolarizing to hyperpolarizing. The change occurred over the
      first 4 days in co-culture or in ACM but took more than 2 weeks in neurons
      cultured on PDL alone. 5. The intrinsic, elementary properties of GABAA
      receptor/Cl- channels including open time and unitary conductance changed
      independently of the presence of astrocytes or ACM. Mean open time of the
      dominant kinetic component decreased and conductance increased with time in
      vitro. 6. In sum, astrocytes accelerate the developmental change in the Cl- ion
      gradient extrinsic to GABAA receptor/Cl- channels, which is critical for
      triggering Ca2+ entry, without influencing parallel changes in the intrinsic
      properties of the channels.

PMID- 9596806
TI  - A slow calcium-dependent component of charge movement in Rana temporaria cut
      twitch fibres.
AB  - 1. Charge movement was studied in highly stretched frog cut twitch fibres in a
      double Vaseline-gap voltage-clamp chamber, with the internal solution containing
      either 0.1 mM EGTA or 20 mM EGTA plus 1. 8 mM total Ca2+. 2. Fibres were
      stimulated with TEST pulses lasting 100-400 ms. Replacement of the external Cl-
      with an 'impermeant' anion, such as SO42-, CH3SO3-, gluconate or glutamate,
      greatly reduced the calcium-dependent Cl- current in the ON segment and generated
      a slowly decaying inward OFF current in charge movement traces. 3. Application of
      20 mM EGTA to the internal solution abolished the slow inward OFF current,
      implying that the activation of the current depended on the presence of Ca2+ in
      the myoplasm. The possibility that the slow inward OFF current was carried by
      cations flowing inwards or anions flowing outwards was studied and determined to
      be unlikely. 4. During a long (2000 ms) TEST pulse, a slowly decaying ON current
      was also observed. When the slow ON and OFF currents were included as parts of
      the total charge movement, ON-OFF charge equality was preserved. This slow
      capacitive current is named Idelta. 5. When Cl- was the major anion in the
      external solution, the OFF Idelta was mostly cancelled by a slow outward current
      carried by the inflow of Cl-. 6. The OFF Idelta component showed a rising phase.
      The average values of the rising time constants in CH3SO3- and SO42- were similar
      and about half of that in gluconate. 7. The OFF Idelta component in CH3SO3- had a
      larger magnitude and longer time course than that in SO42-. The maximum amount of
      Qdelta in CH3SO3- was about three times as much as that in SO42-, whereas the
      voltage dependence of Qdelta was similar in the two solutions. 8. Since the
      existence of Qdelta depends on the presence of Ca2+ in the myoplasm, it is
      speculated that Qdelta could be a function of intracellular calcium release.

PMID- 9596807
TI  - Oxygen-sensing mechanisms are present in the chromaffin cells of the sheep
      adrenal medulla before birth.
AB  - 1. The ability of the fetal adrenal medulla to respond directly to hypoxaemia and
      secrete catecholamines before the development of a functional innervation of the
      gland is essential for intrauterine survival. The cellular mechanisms involved in
      this response to low PO2 are not known, although the presence of oxygen-sensitive
      K+ channels in carotid body chemoreceptor cells and other sites suggests that
      these might underlie the chromaffin cell response. 2. Whole-cell patch-clamp
      techniques have been used to study K+ currents during normoxia and hypoxia in
      chromaffin cells isolated from the adrenal glands of fetal sheep. 3. Two types of
      chromaffin cells were observed, those with a fast inactivating K+ current and a
      larger capacitance and those with a delayed K+ current and smaller capacitance.
      No cell showed both types of current. The fast inactivating current showed
      voltage-dependent inactivation and was blocked by 1 mM 4-aminopyridine,
      characteristics of an IA-type current. The delayed current had two components, a
      TEA-sensitive, Ca2+-dependent current and a component with the kinetic behaviour
      of a delayed rectifier. 4. Both types of current were oxygen sensitive. The IA
      type current was reduced by 27.4 +/- 3.2 % when the PO2 was reduced to about 15
      mmHg. With the delayed current, hypoxia reduced the amplitude by 26.9 +/- 2.4 %,
      largely by reduction of the Ca2+-dependent component. 5. In the presence of
      hypoxia, reduction in the amplitude of these oxygen-sensitive K+ currents would
      increase the frequency and duration of action potentials, leading to increased
      activation of the L-type Ca2+ channels, influx of Ca2+ and the subsequent
      secretion of catecholamines.

PMID- 9596808
TI  - Respiratory modulation of carotid and aortic body reflex left ventricular
      inotropic responses in the cat.
AB  - 1. The reflex changes in the inotropic state of the left ventricle, measured as
      the dP/dt max (maximum rate of change of pressure), occurring in response to
      selective stimulation of the carotid and aortic body chemoreceptors by sodium
      cyanide, were studied in the cat anaesthetized with a mixture of chloralose and
      urethane. 2. The animals were artificially ventilated with an open pneumothorax.
      The heart rate and mean arterial blood pressure were maintained constant. 3. With
      on-going central respiratory activity, stimulation of the carotid bodies caused
      an increase in respiratory movements. Variable changes in left ventricular dP/dt
      max occurred, the predominant response being an increase. The mean change was 8.3
      +/- 2.9 % from a control value of 6850 +/- 450 mmHg s-1. Stimulation of the
      aortic bodies resulted in a smaller increase in respiration or no effect, but a
      significant increase occurred in left ventricular dP/dt max of 19.6 +/- 2.9 %
      from a control value of 6136 +/- 228 mmHg s-1. No significant changes in left
      ventricular end-diastolic pressure occurred in response to stimulation of either
      group of chemoreceptors. 4. Tests of chemoreceptor stimulations were repeated
      during temporary suppression of the secondary respiratory mechanisms: the central
      respiratory drive was suppressed reflexly by electrical stimulation of the
      central cut ends of both superior laryngeal nerves and lung stretch afferent
      activity was minimized by stopping artificial respiration. Carotid body
      stimulation again evoked variable responses, the predominant now being a
      reduction in left ventricular dP/dt max of 3.1 % from a control value of 5720 +/-
      320 mmHg s-1, which was significantly different to that occurring during on-going
      spontaneous respiration. Aortic body stimulation caused an increase in left
      ventricular dP/dt max similar to the response during on-going spontaneous
      respiration. 5. The positive inotropic responses were mediated via the
      sympathetic nervous system, as indicated by their abolition as a result of
      intravenous injections of the beta-adrenoceptor blocking agent, propranolol. 6.
      It is concluded that the carotid bodies exert a small variable effect on left
      ventricular dP/dt max, the predominant positive inotropic response being due to
      the concomitant neurogenic effects of the increase in respiration. In contrast,
      the positive inotropic response to excitation of the aortic chemoreceptors is not
      respiratory modulated.

PMID- 9596809
TI  - Incomplete rematching of nerve and muscle properties in motor units after
      extensive nerve injuries in cat hindlimb muscle.
AB  - 1. Motor units were characterized in partially denervated or completely
      denervated and reinnervated cat medial gastrocnemius (MG) muscles where the
      number of innervating motor axons was severely reduced to determine (1) to what
      extent the nerve and muscle properties are rematched in enlarged motor units, (2)
      whether the normal size relationships between axon size, unit tetanic force and
      contractile speed are re-established, and (3) whether the type of nerve injury
      and/or repair affects the re-establishment of nerve and muscle properties. 2.
      Single MG units were sampled in (1) partially denervated muscles and in
      reinnervated muscles after either (2) crushing or (3) transecting the nerve and
      suturing its proximal end to either the distal nerve stump (N-N), or (4) directly
      to the muscle fascia (N-M). 3. The majority (75-88 %) of motor units in all
      muscles were classified as S (slow), FR (fast fatigue resistant), FI (fast
      fatigue intermediate) and FF (fast fatigable). However, there was an increased
      number of FI and unclassifiable motor units compared to normal. These results
      suggest that motor unit properties are not entirely regulated by the
      reinnervating motoneurone. 4. Despite more overlap in the range of unit force
      between different motor unit types the tetanic force of each type increased in
      all muscles when reinnervated by few (< 50 %) motor axons. This increase in unit
      force was due to an expansion in motor unit innervation ratio. 5. The normal
      relationships between axon size, unit tetanic force, and contractile speed were
      re-established in all muscles except when reinnervated by < 50 % of their normal
      complement of motor units after N-M suture. This lack of correlation was due to
      the reduced fast glycolytic (FG) fibre size and the proportionately greater
      increase in force of the S units. 6. After reinnervation the ranges in fibre
      cross-sectional area within single FF units were very similar to those found
      within the entire FG fibre population. 7. These results show that when few axons
      make functional connections in partially denervated or reinnervated muscles the
      normal relationships between axon size and motor unit contractile properties are
      re-established provided the nerves regenerate within the distal nerve sheath.
      This rematching of motoneurone size and motor unit contractile properties occurs
      primarily because the size of the motor axon governs the number of muscle fibres
      it supplies.

PMID- 9596811
TI  - [Start a new phase of the prevention and control of tuberculosis].

PMID- 9596810
TI  - The mechanics of running in children.
AB  - 1. The effect of age and body size on the bouncing mechanism of running was
      studied in children aged 2-16 years. 2. The natural frequency of the bouncing
      system (fs) and the external work required to move the centre of mass of the body
      were measured using a force platform. 3. At all ages, during running below
      approximately 11 km h-1, the freely chosen step frequency (f) is about equal to
      fs (symmetric rebound), independent of speed, although it decreases with age from
      4 Hz at 2 years to 2.5 Hz above 12 years. 4. The decrease of step frequency with
      age is associated with a decrease in the mass-specific vertical stiffness of the
      bouncing system (k/m) due to an increase of the body mass (m) with a constant
      stiffness (k). Above 12 years, k/m and f remain approximately constant due to a
      parallel increase in both k and m with age. 5. Above the critical speed of
      approximately 11 km h-1, independent of age, the rebound becomes asymmetric, i.e.
      f < fs. 6. The maximum running speed (Vf, max) increases with age while the step
      frequency at remains constant (approximately 4 Hz), independent of age. 7. At a
      given speed, the higher step frequency in preteens results in a mass-specific
      power against gravity less than that in adults. The external power required to
      move the centre of mass of the body is correspondingly reduced.

PMID- 9596812
TI  - [Prevention of tuberculosis through the development of science and technology].

PMID- 9596813
TI  - [Detection of rpoB gene mutation in Mycobacterium tuberculosis by PCR "cold"
      SSCP].
AB  - OBJECTIVE: To evaluate the applicability of detection of rpoB gene mutation in M.
      tuberculosis susceptibility testing. METHODS: 87 M. tuberculosis isolates and 22
      sputum specimens from patients with active pulmonary tuberculosis were detected
      by PCR-SSCP. RESULTS: The sensitivity of PCR for rpoB gene amplification was 100
      pg DNA and 5000 organisms. The rpoB gene could be detected in the all isolates
      tested. In comparison with conventional susceptibility testing methods, the
      sensitivity and specificity of PCR-"cold" SSCP analysis for detecting rifampin
      resistance in 87 M. tuberculosis isolates was 89.6% and 100%, respectively. Among
      22 smear- and culture-positive sputum specimens, only 1 (4.5%) was positive by
      PCR, however, 6 (27.3%) of them were positive by nested-PCR. The "cold" SSCP
      results of these 6 specimens were corresponding to that of the susceptibility
      testing. CONCLUSIONS: The PCR-"cold" SSCP described here can easily and rapidly
      detect rifampin resistance of M. tuberculosis. After increasing the primer
      specificity and amplification sensitivity, the technique might be used for
      detection of M. tuberculosis rifampin resistance in clinical specimen directly.

PMID- 9596815
TI  - [Detection of M. tuberculosis streptomycin-resistant gene].
AB  - OBJECTIVE: To observe the mutations of rpsL gene in M. tuberculosis streptomycin
      resistant isolates, and to develop a new method for detecting drug resistance.
      METHOD: Detecting the rpsL genes with PCR-SSCP and analyzing their codons 43 by
      PCR-RFLP. RESULTS: Strain H37Rv was used as a control. In 22 M. tuberculosis
      clinical isolates, the rpsL PCR fragments from 5 drug-susceptible isolates had no
      differences in the SSCP profiles with strain H37Rv, and were restricted by Mbo
      II. 11 of the 13 streptomycin-resistant isolates showed apparent differences in
      the SSCP profiles and were not digested with Mbo II. 1 of the 4 other drug
      resistant isolates also had apparent SSCP differences and was not digested by Mbo
      II. CONCLUSIONS: The results suggested that the rpsL gene mutation was frequently
      observed in M. tuberculosis streptomycin-resistant isolates, and usually situated
      at codon 43, PCR-SSCP and PCR-RFLP might become a simple, rapid and reliable
      diagnostic test for drug resistance.

PMID- 9596816
TI  - [Relationship between INH-resistance and katG mutation in M. tuberculosis].
AB  - OBJECTIVE: To investigate the molecular mechanism of INH-resistance and the
      relationship between INH-resistance and KatG mutations. METHODS: Use the primers
      designed from the 5' end of the KatG gene to amplify 282bp fragments from INH
      susceptible and -resistant M. tuberculosis isolates. Single strand conformation
      polymorphism (SSCP) for their PCR products were analysed. RESULTS: No katG gene
      sequence deletion was observed, mutations were detected in 17 of 30 INH-resistant
      strains and no gene perturbations were shown in 16 INH-susceptible isolates.
      CONCLUSION: The results suggested that mutation in katG gene was one of the most
      important INH-resistant mechanisms in M. tuberculosis.

PMID- 9596814
TI  - [Application of PCR-SSCP technique in detection of rpoB gene mutation in rifampin
      resistant Mycobacterium tuberculosis].
AB  - OBJECTIVE: To evaluate rpoB gene mutation in rifampin-resistant Mycobacterium
      tuberculosis and its relationship with rifampin resistance. METHODS: Forty
      clinical isolates of Mycobacterium tuberculosis were analyzed by PCR-SSCP
      technique, with H37Rv reference strains as control group. RESULTS: The
      sensitivity of amplication products of 411bp and 258bp were found to be 5
      pg/microliters, 500 organisms per milliliter and 1 pg/microliter, 500 organisms
      per milliliter respectively. rpoB gene belongs to genus specificity.
      Characteristics of SSCP graph of 258bp fragment: Ten sensitive strains were the
      same as H37 Rv. Thirty strains of rifampin-resistant or multidrug resistance,
      including rifampin, were different from H37Rv except for three strains. Positive
      rate was 90%, while specificity 100%. CONCLUSIONS: Results showed that PCR-SSCP
      technique could detect rPOB gene mutation, which might associate with rifampin
      resistance and be helpful to rapid detection and research of rifampin-resistant
      Mycobacterium tuberculosis.

PMID- 9596817
TI  - [Cloning and identification of the Mycobacterium bovis BCG gene for signal
      peptide of antigen 85-B].
AB  - OBJECTIVE: To clone and identify the Mycobacterium bovis BCG gene for signal
      peptide of antigen 85-B. METHODS: Using a polymerase chain reaction technique,
      the signal peptide sequence (position 94 to 211) of antigen 85-B was technique,
      which is one of the major protein secreted by Mycobacterium bovis BCG (Bacille
      Calmette-Guerin). The gene of 117bp fragment was cloned into the SacI and EcoRI
      sites of pBluecript SK, and its sequence was determined by using T7DNA polymerase
      kit. RESULTS: The sequence analysis showed that the sequence of 117bp signal
      peptide was not misincorporated and in 3' end understream of signal peptide the
      12 multi cloning sites for foreign gene could be provided by the recombinant
      plasmid. CONCLUSIONS: The signal sequence of BCG antigen 85-B was cloned into the
      pBluescript plasmid. The recombinant plasmid was called BCG-S01. According to the
      genetic information a secreted protein from M. bovis BCG could be utilized in
      making a useful vaccine vehicle to produce and secrete a vaccinal protein from M.
      bovis BCG living cells.

PMID- 9596819
TI  - [Analysis of short-term effects of short-course intermittent chemotherapies of
      the World Bank Loaned Project].
AB  - OBJECTIVE: To explore the characteristic features of sputum conversion during
      short-course intermittent chemotherapies and the measures of keeping high cure
      rates. METHODS: 1,350 smear positive pulmonary tuberculosis cases in the ten
      research pilot counties of Liaoning province from 1992 to 1993 were selected to
      receive short-course intermittent chemotherapies under full-course supervision.
      The project was supported by the World Bank. The sputum specimens of the cases
      were regularly examined. The effects of the chemotherapies and the measures of
      keeping high cure rate were evaluated according to the situation of sputum
      conversion. RESULTS: The cure rates of initial and relapse smear positive cases
      were 92.5% and 74.6% respectively. It is also found that the therapeutic effects
      were affected by the situation of sputum conversion at the end of intensive
      phase. The cure rate of the cases who failed in initial treatment and continued
      retreatment was only 54%, which was obviously lower than that of the other
      retreatment cases. CONCLUSION: Strengthening the treatment and management at the
      intensive phase can increase the cure rate. It is recommended that more rational
      regimens should be studied and provided to those who fail in initial treatment to
      improve the therapeutic effects.

PMID- 9596818
TI  - [Comparison of local antigen-specific IgA responses with serum IgA response after
      intrapulmonary antigen immunization in healthy subjects].
AB  - OBJECTIVE: To observe local lung and serum antigen-specific IgA response after
      local lung antigen immunization (LLI). METHODS: 11 healthy subjects were
      immunized with keyhole limpet hemocyanine (KLH) through bronchoscopy. 10-14 days
      after immunization, IgA responses were obversed in bronchoalveolar lavage fluids
      (BALF) and serum. RESULTS: LLI induced anti-KLH IgA response in immunized BALF
      and serum, and both were polymeric IgA. Anti-KLH IgA2/IgA1 ratios were greater in
      immunized BALF than in serum. Anti-KLH IgA activity in immunized BALF was
      associated with secretory component (SC), but in serum was not correlated with
      SC. CONCLUSIONS: LLI could induce local antigen-specific IgA production. There
      were markedly differences between the structure and subclass distribution of
      antigen-specific IgA in immunized BALF and serum.

PMID- 9596820
TI  - [Evaluation of the manifestations of bronchial lesions on ligular segments in
      clinical and pathological aspects].
AB  - OBJECTIVE: To evaluate the characteristic findings of lesions on lingular
      bronchus. METHODS: All cases examined by fiberoptic bronchoscopy and (or)
      bronchial biopsy, during the period of 1979-1994, 4,300 in total, were evaluated
      retrospectively. RESULTS: Abnormal lesions were found in 173 cases (4%), among
      them, bronchogenic carcinoma was pathologically documented in 106 cases (61.3%).
      The incidence of cancer in lingular segment was much higher than that in right
      middle lobe, in which 34 (28.3%) of 120 cases were proved. CONCLUSIONS: Paying
      special attention to look for the definite diagnosis on the bronchial lesions was
      suggested since it is important for early diagnosing malignant illness, and the
      value of bronchoscopy was also highlighted by the authors.

PMID- 9596821
TI  - [Advances in the study of drug resistance genes in Mycobacterium tuberculosis].

PMID- 9596822
TI  - [New conception of acute lung injury].

PMID- 9596823
TI  - [Effect of inhaled nitric oxide on endotoxin induced acute lung injury in
      rabbit].
AB  - OBJECTIVE: In order to observe the effects of inhaling nitric oxide (NO) on acute
      lung injury (ALI). METHODS: 24 rabbits divided into 4 groups. Six rabbits injured
      with intravenous E. Coli endotoxin, then followed by treatment of inhaling 80 ppm
      NO in inspired gas. Before and after the infusion of endotoxin, the mean
      pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mPSA) and
      the PaO2 were examined. The venous methemoglobin (MHb) was measured by using
      spectrophometer colorimitry. The extravasculur lung water was evaluated with rate
      of dried to wet lung weight at the end of study. RESULTS: The rabbits injured
      with endotoxin inhaling 80 ppm NO could rapidly reduce the mPAP, increase the
      PaO2 and without inducing significant change of mPSA, MHb and extravasculur lung
      water. CONCLUSIONS: Inhalation of 80 ppm NO can selectively cause pulmonary
      artery dilatation, reduce mPAP, improve pulmonary gas exchange, without producing
      system vasodilation and toxic effects to the rabbits.

PMID- 9596824
TI  - [Effect of 764-3 and ligustrazine on collagen content of extrapulmonary arteries
      during chronic hypoxia].
AB  - OBJECTIVE: Effect of two antifibrotic Chinese drugs, 764-3 and ligustrazine, on
      collagen content in chronic hypoxic pulmonary hypertensive extrapulmonary
      arterial wall were examined. METHODS: Since collagen contains more than 10%
      hydroxyproline by weight and in other proteins there are almost no
      hydroxyproline, collagen content was expressed as micrograms of hydroxyproline.
      Hydroxyproline was determined by calorimetric method after oxidized by chloramine
      T. RESULTS: Both 764-3 and ligustrazine significantly inhibited the increase of
      pulmonary arterial pressure and elevation of hydroxyproline content in
      extrapulmonary arterial wall during chronic hypoxia. CONCLUSIONS: 764-3 and
      ligustrazine may be two hopeful therapeutic drugs for chronic hypoxic pulmonary
      hypertension.

PMID- 9596825
TI  - [Consecutive study on alveolar macrophage release of tumor necrosis factor-alpha
      and platelet-derived growth factor in bleomycin-induced pulmonary fibrosis in
      rats].
AB  - OBJECTIVE: Observe consecutively alveolar macrophage (AM) release of tumor
      necrosis factor-alpha (TNF-alpha) and platelet-derived growth factor (PDGF in
      bleomycin-induced pulmonary fibrosis in rats. METHODS: ELISA method for TNF-alpha
      quantitation; Bioassay method for PDGF assessment. RESULTS: (1) AM TNF-alpha
      release was elevated on 3rd day, peaked on 7th day and then remained at higher
      level than that in control. (2) AM PDGF release was elevated on 3rd day, also
      peaked on 7th day, but then decreased to a near normal level. CONCLUSION: AM
      might play a role in the pathogenesis of pulmonary fibrosis through release of
      TNF-alpha and PDGF.

PMID- 9596826
TI  - [Plasma endothelin-1 and pulmonary hemodynamics at pre-or post exercise in
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate whether plasma endothelin-1 (ET-1) affects the
      pathologic physiologic process of pulmonary hypertension (PH) secondary to
      chronic obstructive pulmonary disease (COPD). METHODS: Forty-six patients with
      COPD who underwent right float-assisted cardiac cather examination and a supine
      ergometer exercise test were classified into 3 groups, that is, group A with PH,
      group B with latent PH and group C without PH. RESULTS: (1) There was a marked
      higher ET-1 level in femoral arterial plasma than in pulmonary arterial plasma
      from group A at pre-or post-exercise or group B at post-exercise. (2) Plasma ET-1
      levels of A and B groups post-exercise are higher that that in group B post
      exercise than that in group C. (3) ET-1 level is also higher in group B post
      exercise than that in group C. (4) There was significant correlation between the
      ET-1 level and mPAP, PVR, PaO2 of group A at pre- and post-exercise or group B at
      post-exercise. CONCLUSION: These finding suggest a role for ET-1 in regulating
      pulmonary circulation of PH secondary to COPD).

PMID- 9596827
TI  - [A study on the expression of three cytokine-receptors and airway hyperreactivity
      in asthmatics after specific provocation].
AB  - OBJECTIVE: In order to study the role of T and B lymphocytes activation in the
      pathogenesis of asthma. METHOD: Pulmonary function tests were performed and
      percentages of three cytokine receptors and the levels of sIL-2R, sIgE and TIgE
      were measured in 31 allergic asthmatics and 12 healthy subjects before and after
      specific provocation. RESULTS: It was found that the serum levels of sIL-2R (t =
      5,719, 5,647 P < 0.01), TIgE were measured in 31 allergic asthmatics and 12
      healthy (t = 6,306, 7,218 P < 0.01) and percentages of CD+23 (chi(2) -23.43,
      18.56 P < 0.01) or CD+(25) (chi(2) = 27.59, 15. 28) cells were significantly
      higher in asthmatics after challenge than those in controls or in asthmatics
      before challenge as well; There were significantly negative correlations between
      sIL-2R and FEV1 or sGaw (r = -0.573, -0.426 P < 0.01), whereas positive
      correlations between sIL-2R and Raw or percent of IL-2R/CD+(25) cells (r = 0.417,
      0.532 P < 0.01); TIgE and percent of Fc epsilon R II/CD+(23) cells (r = 0.603 P <
      0.01), respectively. CONCLUSION: These findings suggest that T cell activation,
      increased serum levels of sIL-2R and increased expression of CD+(25) or CD+(23)
      on cells, may lead to enhanced AHR in allergic asthmatics.

PMID- 9596828
TI  - [The value of dynamic pulmonary perfusion imaging in the diagnosis of
      hepatopulmonary syndrome (HPS)].
AB  - OBJECTIVE: To evaluate the value of 99m-Tc-MAA dynamic pulmonary perfusion
      imaging in the diagnosis of HPS. METHODS: 3 cases of liver cirrhosis with marked
      hypoxemia were studied. RESULTS: The shunt ratios with 100% inspired oxygen were
      elevated (16%, 27% and 11% respectively). Imaging with gamma camera revealed
      radioisotope uptake in their lungs, brains and kidneys. Shunt ratios estimated by
      the quantitative radionuclide method were 43%, 52% and 32% respectively).
      (control < 7%). The contradictory shunt ratio by using the above method results
      from dilation of alveolar capilaries. The same examinations were done in 10 cases
      of healthy controls and other patients. CONCLUSION: The imaging helps diagnosing
      the HPS as well as estimating the degree of shunting.

PMID- 9596829
TI  - [The diagnostic value of flow cytometric DNA analysis of bronchial washing and
      lavage fluids in lung cancer].
AB  - OBJECTIVE: To evaluate the diagnostic value of flow cytometric DNA analysis of
      bronchial washing and lavage fluids in lung cancer. METHODS: The cellular DNA
      contents of bronchial washing and lavage fluids from 68 patients (43 with lung
      cancer and 25 with benign pulmonary disorder) were analyzed by flow cytometry,
      and the diagnostic value of this method in lung cancer was compared with that of
      fiberoptic bronchoscopic biopsy and brushing. RESULTS: The presence of aneuploidy
      was used as a diagnostic criterion, the sensitivity of DNA analysis was 81%, and
      the specificity was 92%. The positive rate of aneuploidy in central lung cancer
      (29) was 83%, and there was no statistical difference when compared with biopsy
      (90%) and brushing (69%). The positive rate of aneuploidy in peripheral lung
      cancer (14) was 79%, significantly higher than biopsy (29%) (P < 0.025) and
      brushing (29%) (P < 0.025). In a few patients from both central and peripheral
      lung cancer groups, biopsy and brushing appeared negative, but aneuploidy was
      obtained from cytometry. CONCLUSION: These results suggest that flow cytometric
      DNA analysis of bronchial washing and lavage fluids may be a valuable adjunctive
      method in the diagnosis of lung cancer, particularly in peripheral lung cancer.

PMID- 9596830
TI  - [The severe side effects of fibrobronchoscopic examination of Shanghai].
AB  - OBJECTIVE: To understand how the severe side effects of fibrobronchoscopy
      happened in Shanghai. METHOD: The 80,998 cases with fibrobronchoscope examination
      in 21 key hospitals of Shanghai were evaluated with questionnaire. RESULTS: 6
      cases died (0.7/10,000) and 78 cases with heavy hemoptysis (9.6/10,000). The
      complication rate seems to be lower than before. CONCLUSION: The reason were
      supposed to be related with the mature technique and preventive measures
      enhanced.

PMID- 9596831
TI  - [Effects of blood pressure day-nocturnal rhythm and endothelin in patients of
      sleep apnea syndrome].
AB  - OBJECTIVE: To analyse the change of blood pressure and endothelin in sleep apnea
      syndrome. METHODS: The ambulatory blood pressure, echocardiogram and plasma
      endothelin in 164 cases of hypertension and normal controls with or without sleep
      apnea syndrome (SAS) were examined. The patients were divided into four groups
      and 41 cases were in each group. RESULTS: The results showed that in a number of
      the patients of sleep apnea with or without hypertension blood pressure day
      nocturnal rhythm disappeared and endothelin increased (18.2 +/- 5.7 ng/L and 13.2
      +/- 4.4 ng/L) The difference of nocturnal blood pressure and endothelin between
      SAS groups and non-SAS groups (11.7 +/- 3.9 ng/L and 4.3 +/- 2.1 ng/L) were
      statistically significant (P < 0.05 and P < 0.01). CONCLUSION: It was suggested
      that the SAS patients might be due to cyclical hypoxemia and nerve-endocrine
      abnormality activating endothelin, and other vasoactive peptides with increased
      blood pressure during sleep and enhance the damage to target organs.

PMID- 9596832
TI  - [Pathological changes in coal miner pneumoconiosis patients' larger airway
      mucosa].
AB  - OBJECTIVE: To study the pathological changes of the larger airway mucosa in coal
      miner pneumoconiosis patients. METHOD: The 23 pneumoconiosis patients' specimens
      were observed under fibrobronchoscope and examined by optical microscope and
      transmission electron microscope, with 19 chronic bronchitis patients (all
      complicated with emphysema) and 5 workers who had the history of dust inhalation
      but no lesions in the lungs as the controls. RESULTS: Scattered macular black
      areas, orifice stenoses and lumen abnormalities appeared in the larger airways of
      the pneumoconiosis patients and the controls who had the history of dust
      inhalation. Fibroplastic proliferation, smooth muscular distortion and lesions in
      various microstructures of columnar ciliated epithelial cells were also seen by
      microscopy among them. CONCLUSION: The results showed that the above pathological
      changes were caused by the direct injuries of coal dust granules to the larger
      airways.

PMID- 9596833
TI  - [A clinicopathological observation of 15 cases of tuberculosis of the appendix].
AB  - OBJECTIVE: To study the clinicopathological features and diagnosis of
      tuberculosis of the appendix. METHOD: Fifteen cases (0.27%) with tuberculosis of
      appendix selected from 5,621 histopathologically examined appendectomy specimens
      between June 1959 and May 1995 were analyzed retrospectively. RESULTS: All the
      cases with tuberculosis of appendix were commonly occurred in the young (< or =
      34 years in 12 cases) and in females (in 11 cases). They were usually secondary
      to tuberculosis elsewhere in the abdomen. By microscopy, proliferative type of
      the lesions were found in 11 cases, while ulcerative type in 4 cases. Fourteen
      cases (accounting for 93%) were clinically misdiagnosed. It was difficult to be
      differentiated from chronic appendicitis, tuberculosis or tumor of the ileocecum
      and malignant tumor of the appendix. CONCLUSIONS: Definite diagnosis of
      tuberculosis of the appendix mainly depend on the histopathological examination.
      It is recommended that in order to avoid misdiagnosis, all the surgically removed
      appendix specimens should be histopathologically examined, no matter whether the
      specimens are macroscopically normal or not.

PMID- 9596835
TI  - [Objective evaluation of non-invasive mechanical ventilation].

PMID- 9596834
TI  - [Ventilator-induced lung injury and the changes in the strategies for
      ventilation].

PMID- 9596836
TI  - [Clinical study of imposed work of breathing caused by the breathing apparatus].
AB  - OBJECTIVE: The imposed work of breathing caused by the breathing apparatus
      (endotracheal tube, breathing circuit tubing, and ventilator's valves) may
      increase patient's work of breathing. To evaluate the imposed work may be useful
      to determine weaning. METHODS: Work of breathing was observed by Bicore CP-100
      breathing monitor at different levels pressure support (PS), T piece and after
      extubation, and the PS level to compensate imposed work of breathing was
      computed. RESULTS: When PS level decreased, patient's work of breathing increased
      significantly. At PS O kPa, the patient's work of breathing increased 57%, which
      was caused by imposed work of apparatus. Because of the resistance of
      endotracheal tube, the patient's work of breathing increased 41% at T piece. The
      PS level that compensated for the imposed work was 0.7 kPa. CONCLUSIONS: When PS
      level was too low or T piece was applied, the imposed work of breathing caused by
      apparatus could markedly increase patient's work of breathing.

PMID- 9596837
TI  - [Prediction of the level of continuous positive airway pressure in the management
      of obstructive sleep apnea syndrome via nasal mask].
AB  - OBJECTIVE: To predict and optimal level of continuous positive airway pressure
      (CPAP) in the menagement of obstructive sleep apnea syndrome (OSAS) by relating
      certain parameters of respiratory disturbance and sleep hypoxemia. METHODS: 18
      patients with OSAS (all male, aged 48 +/- 11 yrs) were enrolled in the study.
      Their actual levels of CPAP (Pm) were determined by a RHK-5500 mode
      polysomnographic system plus BiPAP (ST/D) system. The actuual Pm was related to
      the respiratory disturbance index (RDI) or total time of SaO2 < or = 90% (T S90).
      The correlation regression equations were calculated. 6 patients with OSAS (Group
      A) were treated with the predicted nasal CPAP (predicted Pm) which was derived
      from the regression equation, 8-10 hours per night, for 5-7 nights. 13 patients
      (Group B) receiving nasal CPAP treatment using the actually measured Pm served as
      control. RESULTS: There was a close positive linear correlation between RDI or T
      S90 and actual Pm. Symptoms and polysomnographic parameters improved
      significantly after one course of CPAP treatment in Group A. The efficacy showed
      no signifcant different as compared with that in Group B. CONCLUSIONS: It was
      suggested that RDI or T S90 are of value and simple in predicting the pressuure
      level of CPAP in the management of OSAS with nasal CPAP.

PMID- 9596838
TI  - [Long-term effects of CPAP in obstructive apnea syndrome].
AB  - OBJECTIVE: To study the long term effects with CPAP in OSAS. METHODS: Eighteen
      patients with OSAS were treated by CPAP at home for 3 to 27 months from 1987 to
      1995, comparing the parameters of polysomnography (PSG) before and after
      treatment. RESULTS: (1) all the symptoms of OSAS were improved; (2) The
      parameters of PSG showed that the longest apnea duration from 66 +/- 21s to 43 +/
      24s (P < 0.05); AHI from 66 +/- 16 to 28 +/- 20 n/hour (P < 0.001); The lowest
      SaO2 from 53% +/- 19% to 75% +/- 11% (P < 0.001); (3) Comparing the body weight
      and blood pressure, no significant difference was shown before and after
      treatment with CPAP, but the blood pressure of 6 (50%) OSAS patients with
      hypertension had decreased to normal range. CONCLUSION: Long term treatment with
      CPAP in OSAS were effective, after which, the AHI, lowest level of hopoxemia, the
      longest apnea duration and the sympoms of OSAS were improved. The mechanism could
      be that the patents' breathing control were restored.

PMID- 9596839
TI  - [Differentiation of cytology of BALF between BOOP and UIP].
AB  - OBJECTIVE: BOOP is a disease entity proposed by Epler in 1985, and UIP is
      considered an important disease to be differentiated from BOOP. The aim of this
      study was to identify characteristic features in BALF samples of patients with
      BOOP and UIP. METHODS: Differential cell count and T-cell subpopulation of the
      BALF obtained from 7 patients with BOOP and 7 patients with UIP, both
      histologically verified, were determined. RESULTS: In BOOP patients the ratio of
      lymphocytes and the CD8+ cell in BALF were significantly higher and CD4+/cd8+
      ratio was significantly lower than those of the UIP patients (P < 0.01). In UIP
      patients the ratio of neutrophils in BALF was significantly higher than that of
      the BOOP patients (P < 0.05). CONCLUSIONS: Cytological examination of BALF is
      effective in differentiating BOOP from UIP and it can provide useful information
      about both different pathogenetic processes of the two entities.

PMID- 9596840
TI  - [Detection of Borrelia burgdorferi DNA in granulomatous tissues from patients
      with sarcoidosis using polymerase chain reaction in situ technique].
AB  - OBJECTIVE: To investigate the correlation between sarcoidosis and Borrelia
      burgdorferi (Bb) infection. METHODS: Flagella DNA of Bb were detected in 23
      tissue speciments from patients with confirmed sarcoidosis using polymerase chain
      reaction in situ technique (in situ PCR) and the antibodies to Bb were examined
      in 55 serum samples obtained from the patients by indirect immunoflurescence
      assays. RESULTS: (1) None of granulomatous tissues was found to have Bb DNA in 23
      tissue samples. (2) 30 of 55 (54.6%) patients with sarcoidosis were found
      antibodies to Bb positive, in contrast, six of 60 (10%) normal subjects had
      antibodies against Bb, the positive rate was remarkably higher in patient group
      than that in healty group (P < 0.005). CONCLUSIONS: Bb might not be the causative
      agent of sarcoidosis, the elevated titres of serum antibodies against Bb in
      patients with sarcoidosis is a nonspecific response.

PMID- 9596841
TI  - [Research on IgE responsiveness in asthma patients].
AB  - OBJECTIVE: To understand the relationship between IgE and asthma, and the genetic
      background of IgE. METHODS: The authors measured serum total IgE in 121 healty
      subjects and 100 asthmatic children (CAC-IRMA) and investigated three AA families
      with total IgE evaluation and genetic linkage analysis between IgE and D11S533.
      RESULTS: The IgE cutoff point between low and high was defined at 150 kU/L. There
      were 33.1% population with high level of total IgE. Of the 100 asthmatic children
      96% had higher IgE level than controls, the difference was significant (P <
      0.001). The IgE level of 22 asthmatic children in their releases had no
      significant difference compared with that in their attacks. In 40 members of
      three atopic asthma families, there were 23 persons with high IgE and 15 with
      asthma. In these families high IgE level were found both in male and female and
      the affected person occured in consecutive three generations, which fit to AD
      inheritance. Family 1 and 3 generally showed a high level of IgE, while family 2
      showed low level of IgE. Two point linkage analysis between IgE and D11S533
      showed that there were two recombinants from 22 meioses in the two families with
      a maximum lod score 1.074 at a recombination fraction of 0.05. CONCLUSIONS: Most
      of asthma children have high IgE, which seems obtained from birth. About 1/3
      population have high level IgE who are potential atopic persons. IgE level in
      human beings in inherited by AD mode. IgE gene may be close to 11q13.3-13.4.

PMID- 9596842
TI  - [A study on using rIL-4 and IFN-gamma to regulate IgE synthesis in bronchial
      asthma patients in vitro].
AB  - OBJECTIVE: In order to elucidate the cytokines responsible for altered IgE
      producing in patients with asthma. METHODS: The in vitro effects of recombinant
      interleukin-4 (rIL-4) and interferon-gamma (IFN-gamma) on synthesis of IgE by
      peripheral blood mononuclear cell (PBMC) were studied. RESULTS: Spontaneous IgE
      synthesis by PBMC was significantly increased in patients with asthma compared
      with the controls (t = 4. 4712, P < 0.001). Although the maximum amounts of IgE
      synthesis using PBMC after stimulation with rIL-4 were almost the same both in
      patients with asthma and in controls (t = 0.0620, P > 0.05), the enhancement rate
      of rIL-4-induced IgE synthesis was lower in asthma tic patients than in the
      controls (t = 4. 6719, P < 0.005). IFN-gamma suppressed not only spontaneous but
      also rIL-4-induced IgE synthesis by PBMC in asthmatic patients. The suppressive
      effect on IgE synthesis was more prominent in patients with asthma than in the
      controls (t = 7.1833, P < 0.001). CONCLUSIONS: These results suggest that asthma
      attacks are related to IgE- dependent trigger mechanism; the imbalance of Il-4
      and IFN-gamma in vivo is involved in the development of asthma.

PMID- 9596843
TI  - [The study on noninvasive evaluation of pulmonary artery pressure by the method
      of pulmonary artery flow spectrum in chronic pulmonary disease].
AB  - OBJECTIVE: Pulmonary artery flow spectrum of patients with chronic pulmonary
      disease were studied in order to find excellent Doppler Indexes reflected
      pulmonary artery pressure, and establish multiple regression equation for
      estimating pulmonary artery pressure more accurately. METHODS: During
      catheterization, 54 patients with chronic pulmonary disease were examined by
      echocardiography. Fourteen Doppler indexes of spectrum were compared with the
      pulmonary artery pressure by catheter simultaneously, and multiple regression
      equations were taken. RESULTS: There were significant correlation between Doppler
      indexes PEP/AcT, AcVm, VI/(QTxVmax), RVET/QT and pulmonary artery pressure. Two
      multiple regression equations were deduced: PAPs (kPa) = [9.4 x PEP/AcT-1.4 x
      AcVm-126.1 x VI/(QT x Vmax) + 75] divided by 7.5 and PAPm (kPa) = [7.5 x PEP/AcT
      1.2 x AcVm- 87.7 x VI/(QT X Vmax) + 48] divided by 7.5. CONCLUSIONS: Above two
      regression equations could be used to noninvasively evaluate pulmonary artery
      pressure in patients with chronic pulmonary disease.

PMID- 9596844
TI  - [Effects of reagents used in polymerase chain reaction on sensitivity and
      specificity of detection of Mycobacterium tuberculosis].
AB  - OBJECTIVE: To explore the effects of reagents used in polymerase chain reaction
      on sensitivity and specificity of detection of mycobacterium tuberculosis.
      METHODS: 205 tuberculosis and 105 nontuberculosis cases' sputum specimens were
      examined simultaneously by smear, polymerase chain reaction using three different
      reagents and culture. RESULTS: The positive rates of Mycobacterium tuberculosis
      by polymerase chain reaction using three different reagents were 82.4%, 71.7% and
      61.0% respectively in 205 tuberculosis cases, while 18.0%, 11.4% and 2.8%
      respectively in 105 nontuberculosis cases. The differences between the above
      three different groups was statistically significant (P < 0.005). CONCLUSIONS:
      The sequences of primers and the length of amplified products of different
      reagents may be associated with the positive and the false positive rates of
      Mycobacterium tuberculosis in polymearase chain reaction.

PMID- 9596845
TI  - [Treatment of the secondary hydrocephalus of tuberculous meningitis by lateral
      ventricular drainage and drug injection].
AB  - OBJECTIVE: To decrease intracranial pressure rapidly and cure the secondary
      hydrocephalus of tuberculous meningitis. METHODS: Every case was drained at the
      frontal horn of lateral ventricle of non-predominant cerebral hemisphere,
      injected the mixture of 100 mg isoniazid and 2 mg dexamethasone into the lateral
      ventricle through ventricular drainage tube once every two days or once every day
      in some severe cases. RESULTS: The high intracranial pressure of 23 cases
      suffered from tuberculous meningitis were immediately decreased to normal level.
      The symptoms of 8 cases complicated with brain hernia were quickly improved. The
      cerebrospinal fluid became normal within 2-4 weeks after lateral ventricular drug
      injection. CONCLUSIONS: Lateral ventricular drainage and drug injection can
      obtain good result and provide a new approach to treatment of secondary
      hydrocephalus cases suffered from tuberculous meningitis.

PMID- 9596847
TI  - [Advances in the CSF examination used in the diagnosis of meningeal
      tuberculosis].

PMID- 9596846
TI  - [New techniques of mechanical ventilation: liquid ventilation and partial liquid
      ventilation].

PMID- 9596848
TI  - [Progress and prospects of hysteroscopic operation].

PMID- 9596849
TI  - [Summary of the National Symposium on Gynecologic Endoscopy].

PMID- 9596850
TI  - [Rules of gynecologic endoscopic procedures].

PMID- 9596851
TI  - [Initial experience of 878 patients with operative gynecologic laparoscopy].
AB  - OBJECTIVE: To recommend the operative laparoscopic techniques for gynecology.
      METHODS: Proper application of the technical skills was described on the basis of
      878 operations performed laparoscopically. These skills were divided into three
      groups: level I endocoagulation in 124 cases; level II pretied ligature placement
      and aquadissection in 653 cases; level III electrosection, electrocoagulation and
      knottying, suturing in 101 cases. RESULTS: A total of 866 operations were
      completed laparoscopically without major intraoperative complications. Twelve
      cases were converted to laparotomy due to difficulties. The mean operating time
      for level I, level II and level III group was 49 minutes, 77 minutes and 171
      minutes respectively. The incidence of febrile mobidity for level I, level II and
      level III group was 0.0%, 4.8% and 33.3% respectively. There was one case of
      postoperative haemorrhage associated with infection in the level III group.
      However, no major post-operative complications occurred in the level I-II group
      and the clinical outcome including the overall patients satisfaction was good.
      CONCLUSION: Mastery of operative laparoscopic techniques step by step along with
      the degree of surgical difficulty is madatory, and can deliver optimal clinical
      outcome hopefully. It will also help to expand the use of operative gynecologic
      laparoscopy in a safe and effective way.

PMID- 9596852
TI  - [Clinical evaluation on laparoscopic diagnosis of pelvic endometriosis by heat
      colour test with endocoagulation].
AB  - OBJECTIVE: To assess the value of heat-colour test (HCT) with endocoagulation
      under laparoscopy as a new method for diagnosis of pelvic endometriosis (EM).
      METHODS: Laparoscopic visible examination (LVE), lesion biopsy and HCT with
      endocoagulation were employed for diagnosis of EM in 83 cases of infertility.
      Brown-black colour changes of peritoneal tissue after endocoagulation with
      controlled heating (100 C) indicate EM implants (HCT positive). RESULTS: LVE
      indicated that 35 cases had peritoneal lesions typical of EM in appearance. HCT
      was positive in all cases of visible EM lesions. 48 cases showed no visible
      peritoneal lesions by LVE, but nonpigmented peritoneal EM lesions were detected
      by HCT in 20 of the 48 cases. A variety of gross appearances of nonpigmented EM
      lesions were found in our study including: peritoneal hyperemia (70.9%), circular
      peritoneal defects (12.7%), semitransparant glandular excrescences (10.9%), white
      opacification of the peritoneum (10.9%) and normal appearance (5.4%). 25 biopsies
      were taken from nonpigmented peritoneal lesions in 13 cases. Histology
      examinations revealed the presence of EM in 64.0% of them. CONCLUSIONS: HCT is a
      reliable, sensitive and accurate method for diagnosis of EM. It can overcome
      multiple factors for missing diagnosis of EM by LVE and biopsy. The clinical
      significance of HCT is its ability to detect nonpigmented endometriotic lesions,
      to differentiate the causes of pelvic adhesions, therefore to increase accuracy
      of FIGO EM staging under laparoscopy.

PMID- 9596853
TI  - [Analysis of 158 cases of hysteroscopic surgery for hysteromyoma].
AB  - OBJECTIVE: To treat hysteromyoma by hysteroscopic surgery and to examine the
      treatment results in relation to the extent of surgery. METHODS: 177 patients
      admitted from May, 1990 to Dec. 1994 for abnormal uterine bleeding caused by
      hysteromyoma were subjected to transcervical resection of myoma (TCRM) and/or
      transcervical resection of endometrium (TCRE). Except for 19 patients lost to
      follow-up, 158 patients were closely observed postoperatively. The mean follow-up
      was 29.3 months (range 5-60). These patients were divided into four groups
      according to the extent of the resected myoma. Analysis was based on 3
      categories: the degree of bleeding control, the rate of growth of myoma and the
      need of subsequent surgery, and the treatment results were grouped into:
      perfection, satisfaction and dissatisfaction. RESULTS: The growth of myoma and
      bleeding were controlled in 150 patients (94.9%) after resection. The result was
      much better than that of abdominal myomectomy. The treatment success of total
      resection of pediculate submucosal myoma was as high as 100%. If only > or = 50%
      of sessile submucosal myoma and intramural myoma were resected, the results of
      hysteroscopic surgery were satisfactory although there might be small residual
      intramural myoma or subserous myoma. Long term follow-up showed the residual
      myomata seemed to have stopped growing. CONCLUSION: Transcervical resection is
      one of the effective treatments for abnormal uterine bleeding in hysteromyoma.
      Preoperative accuracy in appraisal of the extent of the myoma to be resected may
      help to correctly predict the prognosis and to improve the surgical cure rate.

PMID- 9596854
TI  - [Tissue and body fluid distribution of antibacterial agents in pregnant and
      lactating women].
AB  - OBJECTIVE: To determine the placental transfer and milk excretion of
      antibacterial agents. METHODS: A prospective study was conducted in pregnant and
      lactating women. The concentrations of 13 agents in tissue and body fluid were
      determined by bioassay or high performance liquid chromatography method. RESULTS:
      The results showed that metronidazole, ofloxacin, chloramphenicol, gentamicin and
      ampicillin crossed blood-placental barrier well, the ratio of fetal tissue or
      amniotic fluid/maternal serum drug concentration was higher than those of the
      other agents. The penetration of penicillins (except ampicillin) and
      cephalosporins was poor, but the drug concentrations were still reached
      therapeutic levels in the most tissues and body fluids. The placental transfer of
      amikacin, clindamycin and erythromycin was slightly higher than beta-lactams. The
      drug concentrations in breast milk was low, except metronidazole and
      erythromycin, the breast milk levels of the two drugs were more than 100% of
      maternal serum levels. CONCLUSION: Based on the results of the study and the
      consideration of possible adverse effects which may affect both the mother and
      the developing fetus as well as antibacterial activities of the drugs, the
      indications and reasonable use of the agents in pregnant and lactating period
      were recommended.

PMID- 9596855
TI  - [Optimum time of maternal blood sampling for prenatal diagnosis with fetal
      cells].
AB  - OBJECTIVE: To investigate the optimum time of maternal blood sampling for
      prenatal diagnosis with fetal cells. METHODS: Zinc-finger protein gene on Y
      chromosome (ZFY) sequences were examined by nested polymerase chain reaction in
      the peripheral blood of 41 pregnant women. RESULTS: 19 pregnant women carrying
      male fetuses, and another 22 women found to carry female fetuses. Among the 19
      pregnant women, ZFY gene were detected in 1/19 (5.3%) cases before the 6th
      gestational weeks, in 13/19 (68.4%) before the 11th weeks, and in 18/19 (95.0%)
      before the 14th weeks. The results of this study clearly demonstrated that the
      gender prediction obviously increased along with the gestational weeks. ZFY gene
      was not detected in the blood of another 22 women carrying female fetuses. The
      final accuracy of 97.8% (40/41) was attained in all cases. CONCLUSION: The
      optimum time of maternal blood sampling is at the 14th week, and the appearance
      of fetal cells in maternal blood was quite case-variable from the 6th to 14th
      weeks.

PMID- 9596856
TI  - [Fetal hemodynamic surveillance of twin transfusion syndrome].
AB  - OBJECTIVE: To evaluate the ratio of peak systolic to least diastolic flow
      velocity (S/D), pulsatile index (PI) and resistance index (RI) of the umbilical
      arterial doppler flow at 20-40 gestational weeks in twin pregnancy for the
      surveillance of twin transfusion syndrome. METHODS: The fetal hemodynamics in 36
      cases of twin pregnancy were monitored by Combison A-ZIPE 4871 with spectral
      doppler ultrasound. RESULTS: The value of S/D ratio and PI in 4 patients with
      twin transfusion syndrome at 32-34 weeks were significantly higher than those of
      normal twin (P < 0.01). Two cases of twin reversed arterial pressure (TRAP), i.e.
      artery to artery transfusion in one of the twin with acardius, were found at 26
      and 26 + 4 weeks respectively. CONCLUSION: The S/D ratio and PI of umbilical
      artery might be useful indices for the surveillance of twin transfusion syndrome.

PMID- 9596857
TI  - [Ultrasonic measurement in the estimation of fetal weight].
AB  - OBJECTIVE: To study simple, reliable ultrasonic measurement in the estimation of
      fetal weight. METHODS: (1) Study of the relationship between ultrasonic
      measurements of fetal biparietal diameter (BPD), cerebellar diameter (CD), femur
      length (FL) and abdominal circumference (AC) and neonatal birthweight in 300
      cases. (2) Prospective study of the effect of abdominal circumference in
      estimation of fetal weight in 330 cases. RESULTS: There was the significant
      correlation between fetal abdominal circumference and neonatal birth weight (r =
      0.866 79). The prospective study in 330 cases showed the predictive value of
      fetal AC was 80.0%. CONCLUSIONS: The ultrasonic measurement of fetal AC is a
      simple and valuable index in estimation of fetal weight.

PMID- 9596859
TI  - [Study on the etiology of pregnancy induced hypertension syndrome].

PMID- 9596858
TI  - [Infection of Ureaplasma urealyticum between parents and their newborns].
AB  - OBJECTIVE: To investigate the relationship of ureaplasma urealyticum (UU)
      infection between parents and their newborns, and the possible influence of the
      modes of delivery on infants UU infection. METHODS: The cervical swab samples
      were obtained from 157 pregnant women around 32-36 gestational weeks for the
      determination of UU by polymerase chain reaction (PCR). In those UU positive
      cases, swab samples were taken both from the their husbands' urethra and the
      their newborns' throat after delivery. RESULTS: UU was detected in 27 pregnant
      women (17.2%), among which it was positive in 66.7% of their husbands, 55.6% of
      the neonates. Out of the 9 infected women whose husbands were negative only 2
      neonates were positive, while 72.2% (13/18) of the neonates found UU infection
      when both of their parents were positive (P < 0.05). The positive rate of
      neonates was 47.1% in the group of vaginal delivery and 70.0% in the cesarean
      section group (P > 0.05). CONCLUSION: The neonatal UU infection is strongly
      associated with UU infection of their parents, and it is mainly an intrauterine
      infection rather than infection aquired during delivery.

PMID- 9596860
TI  - [Association of pregnancy induced hypertension with human leucocyte antigen
      system].
AB  - OBJECTIVE: To examine whether pregnancy induced hypertension (PIH) is correlated
      with a polymorphism of human leucocyte antigen (HLA)-DRB1 in the Shanghai
      population. METHODS: We determined the HLA-DRB1 types of 17 PIH families and 14
      normotension families by DNA typing utilizing the polymerase chain reaction (PCR)
      and hybridization of Dig-labeled sequence specific oligonucleotide (PCR-SSO).
      RESULTS: The antigens frequency and feto-material sharing of HLA-DR4 in PIH were
      increased and relative to that of the controls, and furthermore the 0405 allele
      occurred more often in PLH patients. CONCLUSION: These results suggest that a PIH
      susceptibility gene is associated with HLA-DRB1 0405. We therefore propose the
      following working hypothesis; 0405 allele is presumably due to linkage
      disequilibrium or the possibility that it acts directly as an immune response
      gene; PIH is correlated with DR4 compatibility between PIH mother and fetus which
      leads to failure of the mother's nonresponsiveness to fetal antigen. Lack of
      blocking factor increases the risk for PIH.

PMID- 9596861
TI  - [Tumor necrosis factor in pregnancies associated with pregnancy induced
      hypertension].
AB  - OBJECTIVE: To determine TNF concentrations in maternal plasma, amniotic fluid and
      umbilical blood of normal term pregnant women and women with pregnancy induced
      hypertension (PIH). METHODS: Sixteen normal term-pregnant women as control and
      fourty-six women with PIH were enrolled for study. Maternal plasma including
      antepartum and 72 hours after labor, amniotic fluid and umbilical blood TNF
      concentrations were measured with a sensitive radioimmunoassay. RESULTS: Similar
      levels of TNF were found in the amniotic fluid and umbilical blood between the
      two groups. Before labor, maternal plasma TNF level in PIH was generally higher
      than that in the control, especially a higher level in the moderate and severe
      PIH (P < 0.05). However, the mean levels of plasma TNF were not significantly
      different between the two groups after labor. TNF levels in amniotic fluid were
      significantly lower than those in maternal plasma and umbilical blood. Amniotic
      fluid and umbilical blood TNF levels in PIH with intrauterine growth retardation
      (IUGR) were significantly higher than those in PIH without IUGR (P < 0.05).
      CONCLUSION: Our study demonstrated an increase of TNF level in maternal plasma
      with PIH. The results may show an abnormal maternal immune reaction to the fetus.
      An abnormal higher TNF level may have an effect on the pathogenesis of PIH.

PMID- 9596862
TI  - [The change of serotonin of venous blood in pregnancy induced hypertension].
AB  - OBJECTIVE: To provide evidence to the hypothesis that the involvement of
      serotonin (5-HT) takes part in the pathogenesis of pregnancy induced hypertension
      (PIH). METHOD: 31 pregnant women with PIH and 20 normotensive pregnant women were
      studied in the present study. Venous plasma 5-HT and platelet 5-HT from all
      subjects were measured with spectrometry. RESULTS: The mean platelet 5-HT level
      in PIH group (24.69 +/- 17.79 micrograms/L) was less than that in normotensive
      group (91.06 +/- 47.77 micrograms/L) (P < 0.01). The mean plasma 5-HT level in
      PIH group (48.65 +/- 19.29 micrograms/L) was significantly higher than that in
      normotensive group (35.39 +/- 12.88 micrograms/L) (P < 0.01). CONCLUSION: Plasma
      levels of 5-HT in PIH were elevated significantly, this might be largely caused
      by the increased release of 5-HT by platelet. The results show that elevated
      level of 5-HT in patients with PIH might take part in the pathogenesis of PIH.

PMID- 9596863
TI  - [Magnesium and calcium concentration of peripheral serum and mononuclear cells in
      patients with pregnancy induced hypertension].
AB  - OBJECTIVE: To evaluate the magnesium and calcium concentration of peripheral
      serum and mononuclear in patients with pregnancy induced hypertension (PIH).
      METHODS: Twenty-six patients with PIH and 27 healthy women in their late
      pregnancy were studied. The serum and mononuclear cells magnesium and calcium
      contents were measured with atomic absorption spectrophotometry (fire
      atomization). RESULTS: When compared with the healthy women in their late
      pregnancy, (1) the peripheral serum magnesium and calcium contents in patients
      with PIH decreased significantly (P < 0.01 and P < 0.05), (2) the magnesium
      contents of the peripheral mononuclear cells in patients with moderate and severe
      degrees of PIH decreased significantly (P < 0.001 and P < 0.01), (3) the calcium
      contents of the peripheral mononuclear cells in patients with moderate and severe
      degrees of PIH decreased significantly (P < 0.01 and P < 0.05). CONCLUSION: The
      decrease of magnesium and calcium concentration may be one of the important
      factors responsible for the pathophysiologic changes of PIH.

PMID- 9596864
TI  - [Dose study of methyl carboprost suppository for planned delivery at term].
AB  - OBJECTIVE: To investigate clinical reasonable dose of methyl carboprost
      suppository (15-methyl-PGF2 alpha) for induction of labor. METHOD: A total of 150
      gravidas with singleton pregnancy and cephalic presentation, accepted for
      induction of labor, were randomly allocated into 3 groups: group 1, 15-methyl
      PGF2 alpha 0.100 mg (n = 50); group 2, 0.125 mg (n = 50); and group 3, 0.200 mg
      (n = 50). RESULTS: The success rates of induction were 90.0%, 94.0% and 100.0%
      for group 1, 2 and 3, respectively. As cervical Bishop score < or = 5, the cases
      needed oxytocin intravenous infusion during the active phase were 48.5%, 40.7%
      and 5.0%, respectively; cervical Bishop score > or = 6, the cases were 11.8%,
      13.0% and 0.0%, respectively. There were 3 cases of precipitate delivery in group
      2 and 3. No uterine hyperstimulation occurred in group 1 and 2, while 3 cases of
      uterine hyperstimulation in group 3. CONCLUSION: (1) A single maximum dose of 15
      methyl-PGF2 alpha for term labor induction should be < 0.200 mg. (2) The
      different dose was chosen according to cervical Bishop score, i.e. 0.200 mg or
      0.125 mg for Bishop score < or = 5, and 0.100 mg for Bishop score > or = 6.

PMID- 9596865
TI  - [Clinical study on reduction of postpartum bleeding by methyl carprost
      suppository].
AB  - OBJECTIVE: To observe the effects of methyl carprost suppository on postpartum
      bleeding in normal parturients. METHODS: Three hundred and sixty normal
      parturients were randomized into study group (n = 260) and the control group (n =
      100). Parturients in study group were administered methyl carprost suppository
      tents either vaginally (n = 130) or via the rectum (n = 130). The controls were
      given 10IU oxytocin immediately after the delivery of anterior shoulder of the
      fetus either intramuscularly (n = 50) or intravenously (n = 50). The amount of
      bleeding with in 2 hours postpartum was measured. RESULTS: The mean amount of
      bleeding for parturients who received vaginal or rectal methyl carprost was 146.4
      ml and 134.2 ml, respectively. In contrast, the mean amount of bleeding for
      parturients who received oxytocin intramuscularly or intravenously was 267.9 ml
      and 210.6 ml, respectively. The differences in the amount of bleeding between the
      two groups were statistically significant (P < 0.01), whereas differences between
      the routes of drug administration within each group were not significant (P >
      0.05). CONCLUSION: Methyl carprost suppository is more effective than oxytocin in
      controlling postpartum bleeding. Drug administration through the rectum is easy
      to perform and, therefore, suitable for use in rural areas.

PMID- 9596866
TI  - [Fetal fibronectin and preterm birth].
AB  - OBJECTIVE: To determine whether fetal fibronectin is a sensitive test for the
      diagnosis and prediction of preterm birth. METHODS: Fetal fibronectin was
      measured by enzyme-labeled immunosorbent assay (ELISA) methods in sample of
      cervical secretion from 38 women with threatened preterm delivery (study group)
      and 43 normal pregnanty women with same gestational weeks (control group).
      RESULTS: The positive rate of fetal fibronectin in women with threatened preterm
      birth was significantly higher than that in the normal control group. CONCLUSION:
      Fetal fibronectin is an important marker. It can be used for diagnosis and
      prediction of preterm birth.

PMID- 9596867
TI  - [Basic ovarian status and follicular response to superovulation stimulation in an
      in vitro fertilization and embryo transfer program].
AB  - OBJECTIVE: To study the relationship between patient age, cycle day 3 basal
      ovarian status, serum estradiol (E2) level and the ovarian response in an in
      vitro fertilization and embryo transfer (IVF-ET) program. METHOD: 102 cases and
      102 cycles of IVF-ET patients with regular menstrual period and normal cycle day
      3 basal follicular-stimulating hormone (FSH < 20 IU/L) level were studied. The
      same superovulation regimen was employed. The ovarian response was classified as
      low when follicle number (diameter > 10 mm) was fewer than 3 on the day of hCG
      injection, moderate when the number was 3-14, and high when follicle number
      exceeded 14. RESULTS: (1) Patients older than 35 years tended to be low
      responders; women younger than 30 years usually responded well with production of
      more than 15 follicles. (2) The number of cycle day 3 follicles was positively
      correlated with the number after stimulation with gonadotropin. When total basal
      follicle number in both ovary exceeded 20, ovarian an hyperstimulation syndrome
      should be watched out. (3) On cycle day 3 the diameter of the largest follicle
      was negatively correlated with the ovarian response. In low responders the
      diameter of the largest follicle was usually larger than 4 mm. (4) Despite of the
      different size and number of the cycle day 3 follicles the serum E2 level was
      quite similar. CONCLUSION: Age and basal ovarian status including the number and
      size of the antral follicles are valuable factors to be considered in the
      prediction of ovarian response to the same gonadotrophic stimulation protocol.

PMID- 9596868
TI  - [Diagnostic value of endometrial assessment by transvaginal ultrasonography in
      patients with postmenopausal bleeding].
AB  - OBJECTIVE: To assess the value of endometrial transvaginal sonography in
      diagnosis of patients with postmenopausal bleeding. METHODS: High resolution
      transvaginal ultrasonographic examination was performed in 192 patients with
      postmenopausal bleeding before fractional uterine curettage. The results of
      endometrial sonogram were compared with endometrial histological findings.
      RESULTS: Seventy-seven cases had endometrial thickness < or = 4mm. 74 of them
      (96.1%) showed physiological changes by pathological examination. Only 3 were
      endometrial cancer. In contrast, in 115 patients who had endometrial thickness >
      or = 5mm, 59 (51.3%) had endometrial cancer. CONCLUSION: Transvaginal
      ultrasonography may be used as a screening procedure in patients with
      postmenopausal bleeding. Diagnostic uterine curettage may be avoided in patients
      who had endometrial thickness < or = 4mm.

PMID- 9596869
TI  - [Cytotoxin factors and pregnancy induced hypertension].

PMID- 9596870
TI  - [Tumor necrosis factor and pre-eclampsia].

PMID- 9596871
TI  - [Treatment of internal medical diseases in pregnancy].

PMID- 9596872
TI  - [Clinical analysis of pregnancy with overt diabetes complicated with
      retinopathy].
AB  - OBJECTIVE: To study the outcome of pregnancy in overt diabetes with retinopathy
      and the changes of retinopathy during pregnancy. METHOD: Retrospective study was
      made on 49 pregnancies with overt diabetes from 1981 to 1995. RESULTS: Maternal
      complications and perinatal morbidity were higher in pregnancies with retinopathy
      but there were no significant differences between those with and without
      retinopathy. Retinopathy progressed during pregnancy i 31.1% of the parturients.
      CONCLUSION: Pregnancies with overt diabetes complicated with retinopathy are not
      the indications for terminating pregnancy, but the changes of retinopathy should
      be carefully monitored during pregnancy.

PMID- 9596873
TI  - [Acute fatty liver in pregnancy: a clinicopathologic study].
AB  - OBJECTIVE: To investigate the early recognition and management of milder cases of
      acute fatty liver in pregnancy (AFLP). METHODS: Twelve cases of AFLP treated in
      our hospital during the past two and half years were retrospectively studied with
      emphasis on symptoms, laboratory findings, liver biopsy and maternal
      complications. The 12 cases were classified into 2 groups. Group 1, 6 cases of
      advanced AFLP diagnosed clinically, were treated in the first year of the study.
      Group 2, 6 cases of milder AFLP diagnosed by postpartum liver biopsy, were
      treated during the last one and half years of the study. RESULTS: The mean
      gestational age at onset was 34 +/- 3 weeks. In the early stage, all cases had
      malaise, nausea, loss of appetite and epigastric distress followed by jaundice in
      the third trimester of pregnancy. Laboratory findings included raised
      transaminases (< or = 300 IU/L) and total serum bilirubin (32.5-510.8 micro
      mol/L) levels, hypoalbuminemia (18-30 g/L), hypofibrogenemia (< 2.4 g/L),
      prolonged prothrombin time and prolonged partial thromboplastin time. Maternal
      complications were frequent including hepatic encephalopathy (9), ascites (9),
      hypoglycemia (7), renal failure (3), hematemesis (4), preeclampsia (6), and
      postpartum hemorrhage (5). Cesarean sections were performed in 7 cases. In group
      2, both mother and fetuses had 100% survival. However, the mortality of the
      mothers and fetuses in group 1 were both 50%. CONCLUSIONS: With increasing
      awareness, especially in the early recognition of AFLP cases and prompt
      progressive management, including early termination of pregnancy and large dose
      infusion of fresh frozen plasma, the prognosis of AFLP is obviously improved.
      Percutaneous liver biopsy should be done when the coagulation tests became normal
      and the amounts of ascites decreased after delivery.

PMID- 9596874
TI  - [Clinical analysis of 39 cases of hepatitis E in pregnancy].
AB  - OBJECTIVE: To introduce clinical manifestations and treatment of hepatitis E in
      pregnancy. METHODS: Thirty-nine cases of hepatitis E in pregnancy, were analysed
      from June. 1992 to Jun. 1994, retrospectively on its epidemiologic
      characteristics, clinical manifestations and prognosis. RESULTS: The prognosis of
      sporadic cases of hepatitis E in pregnancy was good and its main complications
      were premature rupture of membranes, uterine inertia and fetal distress.
      CONCLUSIONS: Sporadic case is the main form of hepatitis E in pregnancy in
      Beijing. Active treatment and intensive monitoring would improve its prognosis.

PMID- 9596875
TI  - [Mean corpuscular volume and red blood cell volume distribution width in the
      diagnosis of iron deficiency anemia in pregnancy].
AB  - OBJECTIVE: To evaluate the value of combined measurement of mean corpuscular
      volume (MCV) and red blood cell volume distribution width (RDW) in the diagnosis
      of iron deficiency anemia in pregnancy. METHODS: Hemoglobin concentration (HGB),
      MCV, RDW, serum iron concentration (Fe), total iron binding capacity (TIBC) and
      transferrin saturation percentage (TS%) were simultaneously assayed in 605
      pregnant women at prenatal examination. The results in different groups were
      analysed. RESULTS: There were 68 cases in iron deficiency anemia group, 57 cases
      in non-iron deficiency anemia group and 480 pregnant women in normal group. RDW
      was significantly increased and MCV greatly decreased in iron deficiency anemia
      group as compared with that in normal group and non-iron deficiency anemia group.
      There were no differences in both MCV and RDW between normal group and non-iron
      deficiency anemia group. CONCLUSIONS: Low MCV and high RDW were the
      characteristic changes of iron deficiency anemia in pregnancy. We recommend the
      use of RDW and MCV in the initial classification of anemia in pregnancy.

PMID- 9596876
TI  - [Bacterial vaginosis in pregnant women].
AB  - OBJECTIVES: To determine the prevalence of bacterial vaginosis (BV) in pregnant
      women and to assess the association between BV and adverse pregnancy outcome.
      METHODS: Bacterial vaginosis was screened in 380 healthy pregnant women during
      different gestational weeks by clinical features and Grams stained vaginal
      smears. The pregnancy outcome of these gravidae was followed up. RESULTS: The
      prevalence of BV in pregnant women was 6.8% (26/380). The incidence of puerperal
      infection, neonatal infection, and jaundice of newborn were higher in women with
      BV than those without BV (14.3%, 9.5%, and 23.8% v.s. 2.2%, 1.3%, and 5.4%,
      respectively P < 0.05, P < 0.05, P < 0.005). CONCLUSION: Pregnant women with BV
      are associated with maternal infection, neonatal infection, and jaundice of
      newborn. It is necessary to treat BV during pregnancy.

PMID- 9596877
TI  - [Regulation of ovarian follicular development by epidermal growth factor in IVF
      superovulation cycles].
AB  - OBJECTIVE: To study the role of epidermal growth factors (EGFs) in the regulation
      of ovarian follicular development in in vitro fertilization (IVF) superovulation
      cycles. METHODS: In situ hybridyzation and immunochemistry were used to locate
      EGF, transforming growth factor alpha (TGF alpha) and their receptor (EGFR) in 10
      normal ovarian specimens and in 5 granulosa cell samples obtained from IVF egg
      retrieval procedure. Radioimmunoassay was used for 6 sex hormones and
      radioreceptor assay for EGFs (mainly including EGF and TGF alpha) determinations
      in the serum and follicular fluid. RESULTS: (1) EGF was not detected in the
      ovary, while EGFR and TGF alpha were found to be present in human granulosa
      cells. (2) Serum EGFs levels increased with the development of follicles, and
      EGFs levels in the follicular fluid were higher than those of the matched plasma.
      No correlation was found between EGFs and sex hormones. CONCLUSIONS: TGF alpha
      but not EGF might be synthesized locally, acting on the granulosa cells in an
      autocrine fashion through EGFR in granulosa cells. Serum EGFs levels (including
      EGF and TGF alpha) might be stimulated by exogenous gonadotropins.

PMID- 9596879
TI  - [Chlamydia trachomatis and Ureaplasma urealyticum infection in patients with
      tubal pregnancy].
AB  - OBJECTIVE: To explore the relationship between genital infections with chlamydia
      trachomatis (CT) and ureaplasma urealyticum (UU) and tubal pregnancy. METHODS: 34
      patients with tubal pregnancy (case group), 28 women undergoing tubal ligation
      (control group A) and 40 women with normal early intrauterine pregnancy (control
      group B) were investigated as a case-control study. The polymerase chain reaction
      (PCR) technique was used to detect CT DNA and UU DNA in samples from the
      secretion of cervix, fallopian tube and pelvic fluid. RESULTS: Case group was
      more likely to have detectable CT DNA (47.1%) and UU DNA (55.9%) from cervical
      secretion than control group A and B (P < 0.05). CT DNA detective rate from
      fallopian tube was significantly higher in case group than the control group A
      (26.5% versus 3.6%, P < 0.05). There were no significant differences in the
      positive rates of UU DNA from fallopian tube, CT DNA and UU DNA from pelvic fluid
      between case group and control group A. CONCLUSION: There is a strong association
      between tubal pregnancy and genital infection with CT and UU.

PMID- 9596878
TI  - [Sweat gland carcinoma of the vulva, report of 7 cases].
AB  - OBJECTIVES: To report the clinical and pathologic features and to evaluate the
      treatment results of 7 cases of sweat gland carcinoma of the vulva. METHODS: The
      clinical records of the 7 cases of sweat gland carcinoma of the vulva, admitted
      to our hospital for treatment between December, 1974 and December, 1994, were
      reviewed. The data including clinical and pathologic features, treatments and
      posttreatment follow-ups. Five of the 7 cases were referred from other hospitals,
      4 followed by local resection and 1 with recurrence 7 years after surgery.
      RESULTS: 5/7 of the cases were alive for more than 5 years. One of the 5 cases
      recurred twice at 7 and 11 years after the initial treatment and each time
      remedied by radiotherapy, but eventually died of tumor with pulmonary metastasis
      at the 17th year. Two died within 5 years after treatment; one from cerebral
      hemorrhage and the other from extensive cancer metastasis 1 year and 9 months
      after surgery. CONCLUSIONS: The prognosis of sweat gland carcinoma of the vulva
      is fairly good. Wide local resection of the vulva or radical vulvectomy is the
      treatment of choice.

PMID- 9596880
TI  - [Medicated stainless steel ring-165, medicated gamma-intrauterine devices and
      TCu220C: a multicenter comparative study].
AB  - OBJECTIVE: A five-year multicenter comparative study was conducted to observe the
      clinical efficacy, side effects, and menstrual blood loss (MBL) of medicated
      stainless steel ring 165 (MSSR-165), medicated gamma-Intrauterine devices (gamma
      IUD) (both containing indomethacin and copper) and TCu220C for exploring new
      kinds of IUD to reduce MBL after IUD insertion. METHODS: MSSR-165 and medicated
      gamma-IUD, with TCu220C as a control, were randomly inserted (one thousand in
      each group) in women 12 hospitals nation wide in October 1988. Follow-ups were
      performed at the time of 3, 6, 12, 24, 36, 48 and 60 months after IUD insertion.
      The efficacy of the IUDs was calculated with life table method. A quantitative
      comparison of MBL was made before and 3, 6, 12, 24, 36 and 60 months after the
      IUD insertion in 20 volunteers. RESULTS: At the end of 5 years, the pregnancy
      rates of MSSR-165, medicated gamma-IUD and TCu220C were 3.2, 2.7 and 3.2. The
      expulsion rates were 7.7, 2.3 and 2.4, while the removal rates for medical
      reasons were 5.0, 3.8 and 6.4. The cumulative continuation rates were 79.8, 88.7
      and 84.9 per 100 women respectively. The average total bleeding time in the first
      year of MSSR-165 was 22 days, the shortest one among the three IUDs. The
      quantitative comparison of MBL showed that the gamma-IUD reduced the MBL and the
      TCu220C increased the MBL apparently. CONCLUSION: With good clinical efficacy,
      short menstrual bleeding time, as well as the same appearance and insertion
      technic as stainless steel ring, the MSSR-165 will be easily accepted at the
      grass root level. The gamma-IUD had good clinical efficacy and higher
      continuation rate, whereas the side effect of bleeding was not obvious. Both
      medicated SSR165 and gamma-IUD could be recommended for promotion.

PMID- 9596881
TI  - [Relation between ovarian cancer and gonadotropin and its receptors].

PMID- 9596882
TI  - [Apoptosis and malignant gynecological tumors].

PMID- 9596883
TI  - [The effects of vibratory acoustic stimulation on fetal heart rate and body
      movement of normal fetuses at different gestational ages].
AB  - OBJECTIVE: To study the effects of vibratory acoustic stimulation (VAS) on fetal
      heart rate (FHR) and fetal movement (FM) of normal fetu at different gestational
      ages. METHOD: 435 normal second and third-trimester pregnancies were studied
      using real time ultrasonography. FHR baseline was recorded. Then a five-second
      VAS was given and FM and (or) FHR was observed. The results of vibroacoustic
      stimulation testing (VAS-T), sound-provoked fetal movement (SPFM) and the
      amplitude of FHR acceleration were evaluated. RESULTS: (1) The fetus started to
      response to VAS from the 24th gestational week, but most could not reach the
      diagnostic criteria of VAS-T. The responses of FM were normal. (2) From 28 week
      on, 90% of the fetu showed marked FM and acceleration of FHR after VAS. Over 98%
      of the term babies were reactive. (3) The detective rates of SPFM appeared
      significantly earlier than that of VAS-T. CONCLUSION: It suggested that the
      development of fetal nervous system was matured at 28 weeks, and the development
      of motor nerves was earlier than that of the autonomic nerves.

PMID- 9596884
TI  - [Effects of amniotic fluid embolism-like plasma on isolated perfused rabbit
      lungs].
AB  - OBJECTIVE: In order to investigate whether amniotic fluid could induce the
      release of mediators from blood cells which would damage the lungs, an isolated
      perfused rabbit lung (IPRL) was exposed to amniotic fluid embolism-like plasma
      (AFEP) and the injury of AFEP to lungs and the protective effects of ibuprofen
      were studied. METHODS: 10 ml human amniotic fluid and 50 ml heparized rabbit
      blood were incubated together with or without ibuprofen (600 micrograms) at 37
      degrees C for 30 min and centrifuged. Supernatants were taken and were referred
      to as AFEP or ibuprofen AFEP. IPRL was perfused with AFEP, ibuprofen AFEP, simple
      amniotic fluid (SAF), supernatant of amniotic fluid (SnAF), rabbit plasma (RP)
      and control NS. The changes of pulmonary artery pressure (PAP), respiratory
      pressure (RP) and lung weight were recorded by computer and compared with control
      NS group. RESULTS: In groups of SAF, SnAF and RP PAPs were slightly elevated
      (0.13-0.6 kPa, P > 0.05), and lung weights were not changed. AFEP induced the
      increase of PAP (3.52 +/- 0.64 kPa, P < 0.05) and lung weight (4.0 +/- 1.0 g, P <
      0.01) with the development of lung edema. Administration of ibuprofen prevented
      partially the APEP-induced increase of PAP (1.87 +/- 0.43 kPa, P < 0.05) and lung
      weight (0.4 +/- 0.3 g, P < 0.01). CONCLUSION: Amniotic fluid may induce the
      release of mediators from blood cells, and the latter is the important cause
      resulting in the pathological changes of lungs in amniotic fluid embolism.
      Ibuprofen may reduce partially the APEP-induced lung injury.

PMID- 9596885
TI  - [Detection of hepatitis C virus markers in colostrum].
AB  - OBJECTIVE: To evaluate the possibility of hepatitis C virus (HCV) transmission
      through lactation by detection of HCV markers in colostrum. METHODS: Anti-HCV
      IgG, anti-HCV IgA and anti-HCV IgM antibodies in colostrum and sera were detected
      by indirect enzyme linked immunosorbent assay (ELISA), and HCV RNA was tested by
      reverse-transcription polymerase chain reaction simultaneously. RESULTS: Among 35
      samples of colostrum from puerperants with anti-HCV IgG-positive sera, anti-HCV
      IgA, anti-HCV IgG, and anti-HCV IgM were detected in 19, 6 and 1 samples
      respectively. Fourteen of the 35 sera samples were HCV RNA-positive, and only 2
      of colostrum samples showed HCV RNA-positive. A significant difference (P < 0.01)
      was found between the HCV RNA positive rates of sera and colostrum. CONCLUSIONS:
      IgA was the predominant anti-HCV antibodies in the colostrum from puerperants
      with anti-HCV IgG-positive sera. The HCV RNA-positive rate of sera was markedly
      higher than that of colostrum. It is presumed that puerperants with anti-HCV IgG
      positive sera, especially those with both anti-HCV IgA-positive and HCV RNA
      positive colostrum, are most likely to transmit HCV through lactation and cause
      their infants to be infected by HCV.

PMID- 9596886
TI  - [Endocrine differences between patients with luteal phase deficiency and
      inadequate endometrial response].
AB  - OBJECTIVE: To study the difference of endocrine characteristics between patients
      with luteal phase deficiency (LPD) and inadequate endometrial response (IER).
      METHODS: Serum estradiol (E2), progesterone (P), follicle-stimulating hormone,
      luteinizing hormone and prolactin levels were determined by radioimmunoassay in
      cycles of LPD, IER and normal controls. Contents of endometrial cytoplasmic
      estradiol receptors (ERc), nuclear estradiol receptors (ERn), cytoplasmic
      progesterone receptors (PRc) and nuclear progesterone receptors (PRn) were
      determined by dextran coated charcoal assay in the same cycle. RESULTS: Serum E2
      and P levels in the luteal phase of patients with LPD were significantly lower
      than those of normal group (P < 0.001), no significant difference of endometrial
      estrogen receptor and progesterone receptor contents was found between the two
      groups (P > 0.1). Serum E2 levels in both follicular and luteal phase of IER
      patients were significantly lower than those of normal groups (P < 0.001), but
      serum P levels in luteal phase of the two groups showed no difference (P > 0.1).
      The contents of ERc and PRn in proliferative phase and PRc contents throughout
      the menstrual cycle were also lower than those of the normal group (P < 0.001, <
      0.001 and < 0.05 respectively). CONCLUSIONS: These results indicate that LPD and
      IER are two distinct entities in terms of endocrine characteristics. To
      distinguish underdeveloped endometrium caused by either LPD or IER is the key to
      choose appropriate treatment.

PMID- 9596887
TI  - [Morphologic changes of endometrium in patients with ectopic pregnancy].
AB  - OBJECTIVES: To study the morphologic changes of endometrium in patients of
      ectopic pregnancy. METHODS: The pathologic appearance of endometrium obtained
      during uterine curettage in 217 cases of ectopic pregnancy in our hospital were
      analysed retrospectively. RESULTS: Seven types of endometrial changes were
      observed: (1) decidua and/or Arias-Stella (A-S) reaction 147 cases (67.74%), (2)
      hypersecretory changes 13 cases (5.99%), (3) asynchronous secretory changes
      between the glands and the stroma 27 cases (12.44%), (4) partial secretory and
      partial proliferative changes in glands 18 cases (8.29%), a type of small A-S
      gland was found in 11 of them, (5) early, mid, or late secretory changes 9 cases
      (4.15%), (6) proliferative changes 2 cases (0.92%) and (7) glandular-cystic
      hyperplasia 1 case (0.46%). The above morphologic changes of endometrium were
      correlated with the occurrence and duration of vaginal bleeding and the urinary
      hCG levels. CONCLUSION: The appearance of decidua and A-S reaction should not be
      considered the only diagnostic basis for ectopic pregnancy. Patient's history and
      laboratory findings should also be taken into account in order to acquire an
      accurate diagnosis.

PMID- 9596888
TI  - [Analysis of the outcomes of transcervical resection of endometrium in 400 cases
      with menorrhagia].
AB  - OBJECTIVE: To report the efficacy and outcomes of transcervical resection of the
      endometrium (TCRE) in treatment of menorrhagia. METHODS: 400 patients with
      menorrhagia due to fatigue causes who had failed in medical therapy and did not
      desire pregnancy and surgery underwent TCRE under hysteroresectoscope. Among
      them, 72 patients with submucous uterine myoma less than 5cm in diameter had
      their myoma resected simultaneously, 366 cases were followed up postoperatively
      for 3 months to 4 years. RESULTS: TCRE was performed successfully except 16
      cases, giving a success rate of 95.6%. Three cases sustained uterine perforation.
      During follow-up, 146 cases (41.7%) became amenorrhea, 119 (34.0%) had only
      spotting. The remaining 85 (24.3%) had normal periods. 78.3% of the cases who
      previously had dysmenorrhea had relieved their pain. Long-term complications were
      recurrent abnormal uterine bleeding (22 cases 13 of them had a second operation),
      hematometra (5) and adenomyosis (4 cases). CONCLUSION: TCRE is an effective
      procedure in treating menorrhagia and small submucous uterine myoma.

PMID- 9596889
TI  - [Preparation of F(ab')2 fragment of monoclonal antibody COC166-9 and its
      experimental study of radioimmunoimaging for ovarian carcinoma].
AB  - OBJECTIVES: To obtain F(ab')2 fragment of monoclonal antibody (McAb) COC166-9 and
      to perform its radioimmunoimaging (RII) for ovarian carcinoma. METHODS: McAb
      COC166-9 was digested into F(ab')2 by ficin and tested by SDS-PAGE. After
      purification by DEAE-32, F(ab')2, COC166-9 and normal murine IgG (nMIgG) were
      labelled by 131I and injected intraperitoneally into three groups of nude mice
      bearing human ovarian cancer xenografts respectively. 72 hours after injection,
      RII was performed in three groups of mice. RESULTS: The yield of F(ab')2 was 54%,
      about 80% of the maximal theoretical yield. Good immunoreactivity of F(ab')2
      retained with higher ratio of tumor to normal tissue radioactivity (T/NT) than
      that of intact COC166-9. RII showed better result with lower nonspecific
      background than the latter. CONCLUSION: F(ab')2 could be obtained by ficin
      digestion with good yield and immunoactivity as well as better RII than intact
      monoclonal antibody.

PMID- 9596890
TI  - [Targeting delivery of liposomal adriamycin by intra-lymphatic infusion].
AB  - OBJECTIVE: To assess the feasibility of delivering liposomal adriamycin (lipo
      ADM) to the regional lymph nodes via intralymphatic infusion in a rabbits model.
      METHODS: The plasma and tissue ADM levels were measured by high performance
      liquid chromatography (HPLC) at 0.5 hour, 1 hour, 6 hours, 12 hours, 1 day, 7
      days, 14 days, 28 days. RESULTS: The maximum ADM level (Cmax) in the lymph nodes
      of lipo-ADM was 91.23 micrograms/g, which was 2 times higher than that of the
      free-ADM group. The area under the ADM concentrations-time curve (AUC) of the
      regional lymph nodes of lipo-ADM and free-ADM was 138.34 micrograms/day x g-1,
      31.86 micrograms/day x g-1 respectively (P < 0.01). The pathological features
      showed that the lipo-ADM group had more microabscess, necrosis and fibrosis in
      the lymph nodes than those of the free-ADM group. The histological changes of
      heart were absent or slight in the lipo-ADM group. CONCLUSIONS: lipo-ADM has a
      high affinity for lymphatic tissue. Intralymphatic infusion of lipo-ADM may be
      useful for the treatment of lymphnode metastasis in ovarian cancer.

PMID- 9596892
TI  - [A clinical analysis of 153 uterine sarcomas].
AB  - OBJECTIVE: To evaluate the prognostic factors and treatment methods of 153
      uterine sarcomas. METHODS: 153 cases of the uterine sarcoma were eligible for
      this retrospective study. Of the 153 cases, 48 were leiomyosarcomas, 47 mixed
      mesodermal sarcomas, 37 endometrial stromal sarcomas, 8 carcinosarcomas, 4
      sarcoma botryoides, 1 fibrosarcoma, and 8 malignant lymphomas. 81 cases were in
      stage I, 11 stage II, 33 stage III and 11 stage IV. 38 cases were treated by
      surgery alone, 24 by surgery combined with radiation therapy, 50 by surgery plus
      chemotherapy, 23 by surgery plus radiation therapy and chemotherapy, 4 by
      radiation therapy alone, 3 by chemotherapy alone, and 11 by radiation therapy
      plus chemotherapy. RESULTS: The overall 5-year survival rate was 49.0%, and that
      of leiomyosarcomas, mixed mesodermal sarcomas and endometrial stromal sarcomas
      was 46.9%, 34.1% and 69.3% respectively (P < 0.01). The 5-year survival rate of
      lesions limited to the uterus (stage I + II), and that of pelvic cavity invasion
      (stage III) and distant metastases was 59.6%, 25.6% and 10.0% respectively (P <
      0.01. When the uterus was smaller than a 3 months pregnant uterus, the 5-year
      survival rate was 49.9%. When the uterus size larger than a 3 months pregnant
      uterus, the survival rate was 18.8% (P < 0.05). Premenopausals surviving 5-year
      accounted for 56.3% and post-menopausal 28.9% (P < 0.01). CONCLUSIONS: The
      prognosis of uterine sarcoma is significantly associated with histologic type,
      clinical and surgico-pathological stage, uterine size and pre- or post-menopausal
      status. Radiation or chemotherapy alone is palliative. Postsurgical adjuvant
      radiotherapy significantly decreased vaginal and pelvic recurrences rates. A
      combination of surgery, radiotherapy and chemotherapy can reduce pelvic
      recurrence as well as enhance survivals.

PMID- 9596891
TI  - [Prognosis and prognostic factor analysis epithelial ovarian cancer].
AB  - OBJECTIVE: To investigate the prognosis change and prognostic factors of advanced
      epithelial ovarian cancer in recent over twenty years. METHODS: One hundred and
      fourty patients with advanced epithelial ovarian cancer were analyzed. They were
      divided into two groups based on their operation time. 56 patients operated
      before Jan. 1980 were included in the first group, and the other 84 patients in
      the second group. Kaplan-Meier survival curves of the two groups were calculated,
      and Cox model was used to evaluate the prognostic factors of the disease at
      univariate and multivariate levels using SPSS and SURVCALC software. RESULTS:
      There was no pathological difference in between the two groups, but the patients
      in the second group received more aggressive chemotherapy. The overall 1-, 2-,
      and 5-year survival rates were 61.2%, 32.1%, and 8.5%, respectively. In the first
      group they were 42.3%, 29.6% and 4.5% respectively and in the second group 69.3%,
      36.2%, and 11.2% respectively. The prognosis of the patients in the second group
      was better than that in the first group, P < 0.05. Univariate analysis revealed
      that stage, grade, residual tumor size and chemotherapy were significant
      predictors of patients' outcome. COX regression analysis identified that they
      were all independent prognostic factors. The patients with advanced, low grade,
      residual tumor (> 2 cm) had poor prognosis. The prognosis of the patients who
      received equal or more than four, especially six cycles combined chemotherapy was
      improved. CONCLUSION: The prognosis of the patients with advanced ovarian cancer
      has improved in recent over 10 years, higher optimal cytoreductive rate and equal
      or more than six cycles combined chemotherapy are important measures for the
      better prognosis of advanced ovarian cancer.

PMID- 9596893
TI  - [The treatment of lymph nodes metastases of stage I and II cervical carcinoma].
AB  - OBJECTIVE: To investigate the treatment methods of nodal metastases of stages I
      and II cervical carcinoma. METHODS: Surgical data of 84 patients with stages I
      and II cervical carcinoma were analyzed. All patients underwent extensive
      abdominal hysterectomy and bilateral pelvic lymphadenectomy, 18 of whom received
      systematic resection of periaortic metastatic lesions. The method of isolation of
      the ureters from lateral exterior were performed on 45 patients. Wertheim-Meigs'
      operation was performed in 39 patients and preoperative lymphangiography and
      dyeing in 40 patients, followed by radiotherapy and chemotherapy. RESULTS: 77
      cases were followed up for more than five years, 55 (71.4%) were alive. In the
      patients with one node involved, the survival rate was 85.7%, and in those with
      two or more nodes involved it was 63.3%. The survival rate of the
      lymphangiography group was 80.0%, and that of the control group 62.2%. The
      recurrent rate of cardinal ligament nodes was 2.2% in the patients with lateral
      isolation of the ureters and was 17.9% in the Wertheim-Meigs' group. The survival
      rate of patients with periaortic metastasis was 52.9%. CONCLUSIONS: Lateral
      isolation of the ureters and resection of cardinal ligaments with their lymph
      nodes preoperative lymphangiography and dyeing, and resection of periaortic
      metastatic nodes could reduce nodal recurrence and raise the five year survival
      rate.

PMID- 9596894
TI  - [Decidual granular lymphocytes and pregnancy].

PMID- 9596895
TI  - [The monitoring of post cesarean section uterine scal with B-ultrasonographic and
      clinical detections].
AB  - OBJECTIVE: To find out an effective method for monitoring the healing of uterine
      incision after cesarean section. METHODS: 1,145 patients with cesarean section
      were monitored by B-ultrasonography. In 19 patients who revealed fluid mass in
      uterine incision, 10 cases were treated by percutaneous drainage under
      sonographic guidance and 9 cases as control. RESULTS: According to sonographic
      characteristics, uterine incision healing can be divided into three conditions:
      normal type revealing a smooth strong echo's light band in uterine incision
      (93.97%), inflammatory type revealing an uneven parenchymatous light mass
      (3.67%), and fluid mass with inflammation revealing a complex light mass with low
      echo's or anechoic area (2.36%). There were abnormal clinical signs in most cases
      of inflammation. The percutaneous drainage therapy showed marked effect.
      CONCLUSIONS: The monitoring of uterine incision healing by B-ultrasonography
      plays an important role in preventing late post-partum hemorrhage.

PMID- 9596896
TI  - [Effect of dynorphin A1-13 on hypoxia-ischemic brain injury in neonatal rats].
AB  - OBJECTIVES: To study the secondary pathological changes in the central nervous
      system after injury and the role of dynorphin A1-13 in hypoxi-ischemic brain
      injury in neonatal rats. METHODS: Changes of concentrations of dynorphin A1-13
      immunoreactives in some brain areas at different times after brain injury and the
      effect of injecting 8 microliters dynorphin A1-13 anti-serum into the medulla
      pool on pathological process of brain injury were observed in perinatal cerebral
      hypoxia ischemic rat models prepared by permanent ligation of right common
      carotid artery combined with a temporary systematic hypoxia at 37 degrees C in 7
      day old Wistar rats. RESULTS: Concentrations of dynorphin A1-13 in cortex,
      hypothalamus and hippocampus increased significantly after the injury.
      Microinjection of anti-dynorphin A1-13 serum into the medulla pool 1 h preinjury
      might markedly reduce brain edema and improve the physiological condition.
      CONCLUSIONS: Dynorphin A1-13 plays a role in the pathophysiological process of
      brain hypoxia-ischemia and excessive amount of dynorphin A1-13 had some
      detrimental effect on the process.

PMID- 9596897
TI  - [The effect of platelet activating factor on the biosynthesis of thromboxane A2
      and prostaglandin I2 in human placental villi and umbilical artery].
AB  - OBJECTIVE: To evaluate the effects of platelet activating factor (PAF) on the
      biosynthesis of thromboxane A2(TXA2) and prostaglandin I2(PGI2) in human
      chorionic villi and umbilical arteries. METHODS: We perfused the human placental
      villi and umbilical arteries with PAF (10(-9)-10(-7) mol/l), then quantified TXB2
      and 6-keto-PGF1 alpha in the perfusion fluid by Radioimmunoassay. RESULTS: PAF
      stimulated the biosynthesis of TXA2 and PGI2 in human umbilical arteries and
      chorionic villi in vitro. The production of TXB2 increased from 63.15 +/- 13.24
      pg/mg protein to 127.03 +/- 27.76 pg/mg protein with response to the stimulation
      of PAF (10(-9) mol/L) (P < 0.01). The concentration of PAF (10(-8) mol/L)
      displayed the most optimal stimulating effect on PGI2 biosynthesis in umbilical
      artery samples and the production of 6-keto-PGF1 alpha increased from 6,747.52 +/
      700.31 pg/cm to 8,342 +/- 335.81 pg/cm (P < 0.01). CONCLUSION: PAF may affect
      the fetal-placental circulation by regulating the local levels of PGI2 and TXA2.

PMID- 9596898
TI  - [Human parvovirus B19 infection in perinatal transmission and abnormal fetuses].
AB  - OBJECTIVE: To investigate the perinatal infection of human parvovirus B19 in
      pregnant women and their fetuses. METHODS: 350 sera of normal pregnant women and
      9 sera of abnormal fetuses were investigated by polymerase chain reaction (PCR)
      to check the parvovirus B19 DNA. RESULTS: The prevalence of parvovirus B19 DNA
      was 1.14% and 0.28% in the sera of normal pregnant women and umbilical cords,
      respectively. Parvovirus B19 DNA was detected in 6 sera of pregnant women and
      umbilical cords from 9 abnormal fetuses parvovirus DNA could be detected by in
      situ hybridization in the nuclei of immature hematopoetic cells within fetal
      brain or spleen whose PCR tests were positive. CONCLUSION: The results suggest
      that parvovirus B19 infection do exist in pregnant women and their neonates as
      well as fetuses in our country. PCR and in situ hybridization could provide more
      sensitive, more accurate and specific methods for clinical pathologic diagnosis
      and epidemic investigation.

PMID- 9596900
TI  - [Intracytoplasmic sperm injection in the management of male infertility and
      idiopathic fertilization failure].
AB  - OBJECTIVE: To demonstrate the efficacy of intracytoplasmic sperm injection (ICSI)
      in treatment male infertility and idiopathic fertilization failure. METHODS: 31
      couples received intracytoplasmic sperm injections because of severe oligo
      astheno-teratospermia or idiopathic infertility. Ovarian stimulation was achieved
      by conventional protocol. Transvaginal ultrasound-guided oocyte collections were
      done 36 hours after hCG injection. Only matured oocytes were selected for
      microinjection. RESULTS: 237 oocytes were treated by intracytoplasmic sperm
      injection; normal fertilization and cleavage occurred in 132 of 213 oocytes which
      were survived (62.0% normal fertilization rate). From 1995 to 1996, clinical
      pregnancies were achieved in 8 cases (25.8%). The first ICSI baby was delivered
      on October 3, 1996. CONCLUSION: Intracytoplasmic sperm injection has improved the
      results of IVF-ET treatment in male and idiopathic infertility.

PMID- 9596899
TI  - [Toxoplasmosis infection in pregnant women in Lanzhou].
AB  - OBJECTIVE: To investigate toxoplasmosis (TOX) infection in pregnant women.
      METHODS: The blood samples from 1,250 pregnant women were tested by indirect
      hemaglutination (IHA) for TOX. 1,327 normal cases were included in control group.
      RESULTS: The infection rate of TOX was 7.28% and 8.14% in the study and control
      group respectivity. There was no significant difference between the study group
      and control group (P > 0.05). There was no marked relationship between various
      age groups. (P > 0.05). No significant difference was noted in three gestational
      periods. Most pregnant women with of TOX infection were active and recent.
      CONCLUSION: Pregnancy did not increase the chance of TOX infection.

PMID- 9596901
TI  - [Detection of Chlamydia trachomatis and Ureaplasma urealyticum from aborted
      tissues by polymerase chain reaction technique].
AB  - OBJECTIVE: To study the prevalence of Chlamydia trachomatis (CT) and Ureaplasma
      urealyticum (UU) infection in spontaneous abortion patients. METHODS: CT and UU
      in aborted tissues were determined by polymerase chain reaction (PCR) technique
      in 45 spontaneous abortion patients (abortion group) and 25 artificial abortion
      cases (control group). RESULTS: The detective rate of CT and UU was 42.2% and
      33.3% respectively in the abortion group. As compared with the control group
      significant difference (P < 0.01, P < 0.025) was shown. The detection rate of
      mixed CT and UU is 8.9%. CONCLUSION: CT and UU are important infection factors
      which may cause spontaneous abortion. PCR examination of the aborted tissue can
      submit an accurate, rapid microorganic diagnosis of CT and (or) UU infection.

PMID- 9596902
TI  - [Establishment and characterization of a xenografted human cervical carcinoma in
      nude mice and homologous cell line in vitro].
AB  - OBJECTIVE: To establish a xenografted tumor strain of human cervical carcinoma in
      nude mice and homologous cell line in vitro. METHODS: A human well differentiated
      cervical squamous cell carcinoma derived from a surgical specimen was
      transplanted in the subcutis of nude mice. The xenograft was cultured to
      establish a cell line in vitro. A series of characteristics of the grafts and the
      cells were examined. The established cell line was cloned by single cell
      detaching flask. Non-serum culture of the cells was tried. RESULTS: The
      xenografts were successively passaged for 26 generations during a period of 17
      months. A tumor strain HCC-94V was established, having a high rate of successful
      inoculation rate (92.9%) and was growing steadily. The morphological and
      biological characteristics of its original tumor were preserved. The chromosomal
      analysis revealed a human aneuploid pattern of 9-120 in number. The tumor markers
      detected by immunocytochemical techniques showed high expression, the oncogenic
      products, low expression. Polymerase chain reaction (PCR) showed the same results
      as those of the patients with original tumor tissue, human papilloma virus (HPV)
      16 (+), 18 (-). A new human cell line HCC-94 derived from the xenograft, was
      established and maintained for 16 months through 131 passages. Transmission
      electromicroscopy demonstrated the presence of typical desmosomes between the
      cells and many tonofilaments in the cells. Also, the morphology of chromosomes
      showed the characteristics of chromosomes as well as of mutants in the human
      tumor cells. The tumor markers and the oncogenic products of the cells exhibited
      higher expression than that of the original tumor. The HPV 16 and 18 of the
      cells, using PCR, were negative. The cells were highly tumorigenic in nude mice.
      The transplanted tumors resembled the original tumor tissues in morphology and
      were HPV 16 positive. Both cell cloning culture and non-serum culture of HCC-94
      were successful. CONCLUSION: HCC-94V and HCC-94 could be considered as a new
      xenografted tumor strain may provide material and model ideal for further
      investigation of human cervical carcinoma.

PMID- 9596903
TI  - [China-made paclitaxel in the treatment of advanced ovarian cancer: a clinical
      analysis of 32 cases].
AB  - OBJECTIVE: To study the effect and toxicities of China-made paclitaxel in the
      treatment of advanced epithelial ovarian carcinoma. METHODS: Thirty-two patients
      were divided into two groups. single paclitaxel group (SPG): paclitaxel was only
      given to twelve untreated patients or those who had been given only one course of
      chemotherapy at a dose of 175 mg/m2 in 5% glucose 500 ml, i.v. for 3 hours; and
      combined paclitaxel group (CPG): paclitaxel 135 mg/m2 in 5% glucose 55 ml, i.v.
      for 3 hours on day 1 plus cisplatin 70-80 mg/m2 or carboplatin 300 mg/m2, i.v. on
      day 2, was administered to 20 patients with persistent or recurrent tumor after
      platinum based chemotherapy. Four weeks were defined as one course in both
      groups. At least two courses were given except those with tumor progression after
      one course. RESULTS: The overall response rate was 39%. It was 27% and 45% in the
      SPG and CPG. The chief side effects were moderate myelosuppression, peripheral
      neuropathy (myalgia, arthralgia, peripheral neuritis), severe alopecia, etc., but
      no hypersensitivity. One patient died from intestinal perforation. CONCLUSIONS:
      China-made paclitaxel is effective as in treating ovarian carcinoma especially
      for platinum-resistant patients. The toxic effects are tolerable to the patients.

PMID- 9596904
TI  - [Clinical analysis of 15 patients with primary malignant melanoma in the genital
      tract].
AB  - OBJECTIVE: To analyse the clinical characteristics and prognosis of primary
      malignant melanoma in female genital tract. METHODS: Clinical data of 15 patients
      with primary malignant genital melanoma were analysed retrospectively. The tumors
      occurred in the vulva (4 patients), in vagina (9) and in uterine cervix (2). 11
      of them were treated by surgery combined with chemotherapy and immunotherapy, the
      remaining 4 by chemotherapy and immunotherapy only. RESULTS: All cases except one
      were followed up. The survival periods were shorter than 1 year in 5 patients,
      shorter than 2 years in 7. Two were alive for more than 3 years and 1 for more
      than 19 years. CONCLUSIONS: The prognosis of primary malignant melanoma is rather
      poor. Surgery combined of chemotherapy and immunotherapy is the main therapeutic
      approach.

PMID- 9596905
TI  - [Metabolic changes in women with normal pregnancy and pregnancy complicated
      diabetes mellitus].

PMID- 9596906
TI  - [Effects of estrogen on vascular walls].

PMID- 9596907
TI  - [Improve the quality of vaginal delivery].

PMID- 9596909
TI  - [Correction of occipito-posterior position by maternal posture during the process
      of labor].
AB  - OBJECTIVE: To investigate the effect on correction of occipito-posterior (OP)
      presentation by changing maternal posture during labor. METHOD: A prospective
      study was conducted in 120 pregnant women from March 1994 to December 1995. Women
      in labor were instructed to take the lateral posture so that the resultant force
      of the gravity of the fetus, the buoyancy of amniotic fluid, and the intermittent
      uterine contraction may change the fetal position from occipito-posterior into
      occipito-anterior (OA) presentation. Another 120 women were selected as controls.
      RESULTS: (1) In the study group, 106 women (88.3%) delivered vaginally with fetal
      presentation changed from OP into OA, and 14 (11.7%) received cesarean section.
      In the control group, only 20 women (16.7%) delivered vaginally, and 100 (83.3%)
      had cesarean sections (P < 0.001). (2) The average time interval in the study
      group was 302.6 min for the first stage and 59.8 min for the second stage,
      whereas 483.7 min and 156.1 min respectively in the controls. A significant
      difference was noted (P < 0.01). CONCLUSION: It is an effective method for the
      mother to take the lateral posture on the same side of the fetal spine for
      correcting the OP position. The incidence of dystocia may be reduced as well as
      the cesarean section rate. The method in simple and effective, and can be used in
      most of hospitals.

PMID- 9596908
TI  - [Safety and efficacy of intravaginal misoprostol for cervical ripening in the
      third trimester of pregnancy].
AB  - OBJECTIVE: To evaluate the safety and efficacy of intravaginal misoprostol for
      cervical ripening in late trimester. METHOD: A randomized, double-blind, placebo
      controlled trial was conducted. 85 patients with indication for induction of
      labor and unfavorable cervices were randomly assigned to receive either
      intravaginal misoprostol (100 micrograms) or placebo placed in the posterior
      vaginal fornix at one time. The Bishop score, fetal heart rate monitoring and
      Doppler blood flow velocity waveforms were measured before and 12 hours after
      drug insertion. Placenta and decidua were observed histopathologically in some
      cases. Among 85 patients enrolled, 43 received misoprostol and 42 received
      placebo. RESULTS: The mean initial Bishop scores were not significantly different
      between the two groups, while the mean Bishop score in the misoprostol group was
      significantly higher than that in the placebo group (4.4 for misoprostol versus
      1.0 for placebo, P < 0.01). The prevalence of spontaneous labor within 12 hours
      after misoprostol insertion (67.4%, 29/43) was significantly higher than that in
      the placebo group (14.3%, 6/42) (P < 0.01). The average Doppler velocity systolic
      to diastolic (S/D) ratios of umbilical artery, middle cerebral artery, renal
      artery were not significantly different before and 12 hours after drug insertion
      between both groups. There was no significant difference in frequency of abnormal
      fetal heart rate tracings or fetal distress and in the mean Apgar score between
      the two groups. Except the presence of vasodilation in villi vessels in the
      misoprostol group, no significant difference existed between the two groups in
      the placental and decidual histopathological changes. CONCLUSION: Intravaginal
      misoprostol may be an effective and safe cervical ripening agent in late
      pregnancy.

PMID- 9596910
TI  - [Causes of active phase arrest].
AB  - OBJECTIVE: To evaluate factors affecting active phase arrest. METHOD:
      Retrospective study from 1992 to 1994 was performed. A total of 166 pregnant
      women were included, 83 in to the active phase arrest group and 83 in normal
      group. RESULTS: There were significant differences in the average birth weight
      and the prevalence of abnormal fetal presentation between the 2 groups. The time
      length of the latent phase was another factor influencing active phase arrest.
      CONCLUSION: With normal pelvis, the high birth weight, abnormal presentation and
      prolonged latent phase were active phase arrest.

PMID- 9596911
TI  - [Retrospective epidemiological study of pregnancy complicated by heart disease
      during 15 years in Shanghai].
AB  - OBJECTIVE: To investigate the changes of pregnancy complicated by heart disease.
      METHOD: Clinical data of hospitalized pregnant women with heart disease,
      collected from 10 teaching hospitals in Shanghai during 1981-1995, were analysed
      retrospectively. RESULTS: 2,680 of 379,065 deliveries (0.71%) were complicated by
      heart disease during that period. There were a total of 121 maternal deaths, 15
      of them due to heart disease, the mortality of heart disease was 0.56%, and the
      percentage in total maternal deaths was 12.40%. The incidence and mortality rates
      were similar in 1981-1985, 1986-1990, 1991-1995, but the percentage due to heart
      disease increased after the late 1980s. The rates of congenital heart disease
      increased and rhumatic heart disease decreased apparently, the ratio of the
      former to the latter was 1.76:1. The pregnancy induced hypertension heart
      disease, the peripartum cardiomyopathy and the miscellaneous heart disease all
      increased obviously during the 1990s. The heart functions of grade I and II
      accounted for a considerable proportion (85.45%), but the grade IV tended to
      increase during the 1990s. Heart failure occurred in 172 cases, with an incidence
      of 7.6%. The perinatal mortality rate was 7.76%. Cesarean sections were often
      performed in heart disease women. CONCLUSION: Pregnancy complicated by heart
      disease is still one of the major cause of maternal deaths up till now. More
      effective management should be adopted.

PMID- 9596912
TI  - [Colour Doppler ultrasonographic indices in predicting fetal hypoxia and
      acidosis].
AB  - OBJECTIVE: To evaluate the effect of uterine-placental-fetal blood flow velocity
      waveforms (FVWs) on predicting fetal hypoxia and acidosis in high risk pregnancy.
      METHODS: 46 women of normal term pregnancy (normal group) and 32 women of high
      risk term pregnancy (high risk group) were examined with colour Doppler
      ultrasound for their FVWs including maternal uterine artery (UtA), fetal
      umbilical artery (UmA), middle cerebral artery (MCA), and renal artery (RA).
      Umbilical artery blood gases were analysed at delivery in high risk group.
      RESULTS: The resistance index (RI), pulsatile index (PI) and ratio of peak
      systolic to least diastolic flow velocity (S/D) of UtA, UmA and RA were higher
      and the PI, S/D of MCA was lower significantly in the high risk group than that
      of normal the group (P < 0.05). In the high risk pregnancy, when UmA PO2 was less
      than 2.5 kPa, the S/D of UtA, PI, S/D of UmA and RI, PI, S/D of RA were
      increased, and the PI of MCA was decreased (P < 0.05). There were a positive
      correlation between PI of UmA, RA and PO2 pH of UmA, and a negative correlation
      between the former and PCO2 of UmA. But there were a negative correlation between
      PI of MCA and PO2, pH of UmA, and a positive correlation between the former and
      UmA PCO2. CONCLUSION: In the high risk pregnancy, fetal cerebral blood flow
      increased, whereas blood flow of fetal peripheral vessels (especially renal
      vessel) decreases. There is a good correlation between fetal hypoxia and fetal
      blood FVWs. The indices of the fetal blood FVMs can identify fetal hypoxia and
      acidosis.

PMID- 9596913
TI  - [Clinical observation of cardiac pacemaker in pregnant women].
AB  - OBJECTIVE: To study the clinical results in pregnant women with bradycardia
      implanted with cardiac pacemakers. METHOD: Five pregnant women with bradycardia
      were retrospectively studied in our hospital from 1980 to 1996. RESULTS: Four of
      the patients had A-V block, and the other one sinus bradycardia. Classification
      of cardiac function, showed 1 case of class IV, 3 cases of class III, and 1 case
      of class II before implantation of cardiac pacemaker. One case had the pacemaker
      implanted before pregnancy and 4 cases during pregnancy. Cardiac function
      improved significantly after implantation and pregnancies went uneventfully.
      Three women had term living birth by cesarean section, and 2 ended by therapeutic
      abortions safely. CONCLUSION: Bradycardia is a rare and serious complication in
      pregnancy, especially due to A-V block of III degree. Cardiac pacemaker should be
      implanted before pregnancy or at early stage of pregnancy in order to maintain
      adequate heart function. These patients should receive cesarean section.

PMID- 9596914
TI  - [Determination of plasma D-dimer in patients with pregnancy induced
      hypertension].
AB  - OBJECTIVE: To investigate the changes and the clinical significance of plasma D
      dimer in normal pregnant women and patients with pregnancy induced hypertension
      (PIH). METHODS: Using ELISA method, we measured the level of plasma D-dimer in
      160 cases, including 106 normal pregnant women and 25 patients with mild and
      moderate PIH, 18 patients with preeclampsia and 11 patients with eclampsia.
      RESULTS: The value (2.27 +/- 0.92 mg/L) of plasma D-dimer in mild and moderate
      PIH patients was markedly higher than that of normal third trimester pregnant
      women (1.45 +/- 0.38 mg/L, P < 0.01). The value (3.09 +/- 1.65 mg/L) of plasma D
      dimer in preeclampsia patients was markedly higher than that of mild and moderate
      PIH patients (P < 0.01). The value (5.62 +/- 1.34 mg/L) of plasma D-dimer in
      eclampsia patients was markedly higher than that of preeclampsia patients.
      CONCLUSION: Determination of plasma D-dimer level in second and third trimester
      pregnant women was of great significance in diagnosing early PIH and predicting
      the prognosis of PIH.

PMID- 9596915
TI  - [Effect of pretreatment counseling on discontinuation rates in women given depo
      medroxyprogesterone acetate for contraception].
AB  - OBJECTIVE: To investigate the effect of pre-treatment counseling on
      discontinuation rates of 150 mg depo-medroxyprogesterone acetate (DMPA), given
      for contraception. METHODS: A total of 421 women participated, 204 receiving
      intensive structured pre-treatment and on going counseling on the hormonal
      effects and probable side effects of DMPA and 217 receiving only routine
      counseling. All participants were followed up at every 3 months for 1 year. The
      primary endpoint was termination rate, secondary endpoints were frequency of
      medical events and reasons for termination. RESULTS: The most common reasons for
      terminating DMPA were menstrual changes. Although women in the intensive
      structured counseling group reported more menstrual irregularity (39.7%) than did
      women in the routine counseling group (26.3%), study termination rates were
      significantly lower in the intensively structured counseling group than in the
      routine counseling group. At one year, the total cumulative termination rates
      were 11.3% (23/204) and 42.4% (92/217), respectively (P < 0.0001). No pregnancy
      and serious medical events were reported. CONCLUSION: Pre-treatment counseling on
      expected side effects increases the acceptability of DMPA.

PMID- 9596916
TI  - [Comparison of two techniques used in immediate postplacental insertion of TCu
      380A intrauterine device: 12 month follow-up of 910 cases].
AB  - OBJECTIVE: To compare the efficacy of hand-insertion and ring forceps-insertion
      of TCu 380A intrauterine device (IUD) in immediate postplacental insertion
      (IPPI). METHODS: 910 vaginal delivery women in Shanghai received a TCu 380A IUD
      inserted within 10 minutes after delivery of the placenta. Among them, 97.7% were
      primipara. The women were randomly divided into two groups: 470 cases in hand
      insertion group and 440 in ring forceps-insertion group. Using life-tale method
      and X2 test, we compared the expulsion rates and other causes of removal after
      follow-up for 12 months in the two groups. RESULTS: The follow-up rate at 6 and
      12 months were 95.16% and 92.64%, respectively. No uterine perforation and
      infection occurred in the 910 cases, and only one pregnancy in the hand-insertion
      group. Expulsions were the main reason for discontinuation. The 12-month gross
      cumulative expulsion rates were 15.86 and 15.88 per 100 women in the hand
      insertion group and ring forceps-insertion group, respectively, and the removal
      rates due to bleeding and (or) pain were 2.11 and 1.57, respectively. No
      difference was statistically significant (P > 0.05). CONCLUSION: The two
      different insertion techniques do not significantly affect discontinuation rates
      in vaginal IPPI using the TCu 38)A IUD; the TCu 380A IUD appears to be suitable
      for postpartum insertion in Chinese women.

PMID- 9596917
TI  - [Cellular adhesion molecule (CD44) in ovarian tumors].
AB  - OBJECTIVE: To investigate a method of detecting adhesion molecule (CD44) contents
      in ovarian tumors and its clinical significance. METHODS: In 106 patients with
      ovarian tumors (50 benign and 56 malignant), the adhesion molecule (CD44)
      contents in peripheral blood lymphocytes (PBL) and in neoplastic tissues were
      analysed (quantitatively by using flow cytometric-immunological method). RESULT:
      (1) The CD44 contents in the PBL of the patients with malignant tumor were
      obviously higher than those of patients with benign tumors (P<0.05) and than
      those of the control (P < 0.01); (2) Within the group of patients with malignant
      tumors, the CD44 contents in the neoplastic tissues were higher than those in the
      PBL (0.01 < P < 0.05); There was no significant difference in CD44 contents among
      the different histopathological types, whether benign or malignant; (4) The CD44
      contents in the PBL decreased gradually after surgery. CONCLUSION: To analyse the
      CD44 contents in PBL and neoplastic tissues by flow cytometry may be an important
      method or parameter to differentiate benign ovarian tumors from malignant tumors
      and to discover recurrence of metastasis of malignant tumors in early stage.

PMID- 9596918
TI  - [Progress in study of B-model ultrasonography in prediction of fetal weight].

PMID- 9596919
TI  - [In-depth remarks on receptor research].

PMID- 9596920
TI  - [The expression of AT1A receptor and its modulation by benazepril in the renal
      tubulointerstitial lesions induced by ureteral obstruction].
AB  - OBJECTIVE: To study the expressions of angiotensin II 1A receptor (AT1A) both at
      the mRNA level and the protein level and their modulation by an angiotensin
      converting enzyme inhibitor, benazepril, in the renal tubulointerstitial injuries
      induced by unilateral ureteral obstruction (UUO) in rats. METHODS: Six SD rats
      (UUO-T) were administered benazepril in the drinking water (50mg/L). Additional 6
      rats were used as untreated controls (UUO-C). Mean arterial Prossure (MAP) was
      measured at the 10th day after UUO, and then all animals were sacrificed. The
      expressions of AT1A were examined both at the mRNA level by in situ hybridization
      using a subtype-specific probe and at the protein level by an
      immunohistochemistry methods using AT1 receptor antibody in normal rat kidneys
      and the obstructed rat kidneys. RESULTS: MAP was 14.2 +/- 0. 6kPa in the UUO-T
      and 16.6 +/- 0.7kPa in the UUO-C (P < 0.05). Benazepril slowed the
      tubulointerstitial fibrosis (TIF) and reduced the expression of AT1A in the renal
      tubular epithelial cells, the interstitial areas, and the walls of renal
      arteriole in the UUO-T group. CONCLUSION: The increased expressions of AT1A were
      found in the acute renal tubulointerstitial pathogenesis induced by UUO.
      Benazepril may retard the progression of TIF and decrease the expression of AT1A
      in the obstructed kidneys. We conclude that the effects of Ang II on the
      obstructed kidneys may be due to its binding with AT1A.

PMID- 9596921
TI  - [Regulation of myocardium beta-adrenoreceptor pathway in ventricular remodeling
      of heart failure patients].
AB  - OBJECTIVE: To study the role of myocardium beta-adrenoreceptor pathway in
      ventricular remodeling of heart failure patients. METHODS: Beta-adrenergic
      receptor density (Bmax) and the content of cAMP were measured in the papillae of
      left ventricle and blood lymphocyte of 20 patients with heart failure (CHF) (NYHA
      classification II to III). Bmax was investigated by 3H-dihydroalpneolol as
      ligand, cAMP by competitive immunoassay, and left ventricle mass index (LVMI) by
      echocardiogram. RESULTS: The Bmax and cAMP in failing myocardium were
      significantly negatively were correlated with LVMI (r = -0.77, P < 0.01 and r = 
      0.46, P < 0.05 respectively). The Bmax of myocardium and blood lymphocyte in CHF
      patients with NYHA III (63 +/- 12 fmol/mgpro and 514 +/- 115 fmol/10(7) cell),
      was significantly lower than that of NYHA II patients (94 +/- 20 fmol/mgpro and
      702 +/- 138 fmol/10(7) cell, and that in patients with abnormal LVMI (62 +/- 12
      fmol/mgpro and 516 +/- 122 fmol/10(7) cell) decreased more significantly than
      that in normal LVMI patients. Even in normal LVMI patients (92 +/- 21 fmol/ mgpro
      and 682 +/- 146 fmol/10(7) cell), the Bmax of blood lymphocyte was already
      decreased (P < 0.01), when comparing with the controls. The intralymphocyte cAMP
      content was more significantly decreased than that of the controls (P < 0.05).
      CONCLUSIONS: The Bmax can reflect the severity of ventricle remodeling and the
      impairment of myocardium. The regulation of myocardium intracellular messenger
      transduction is earlier than the pathologic structural change of LV remodeling.

PMID- 9596923
TI  - [Application of subtractive hybridization in screening for colorectal cancer
      negatively related genes].
AB  - OBJECTIVE: To search previously uncertained factors that corelated with the
      occurence and development of human colorectal cancer. METHOD: Subtractive
      hybridization technique was employed to screen down-regulated genes of colorectal
      cancer. RESULTS: We obtained 46 clones which highly were expressed in normal
      intestinal mucosa but much lower or none in colorectal cancer. Two of the 46
      clones, SCN6 and SCN19, were accepted by the Genbank Database as novel genes with
      the accession numbers U17714 and U20248. Full length cDNA (2932bp) of SNC6 was
      sequenced, and supposed to encode a protein comprised 271 amino acids, MW30kd,
      which shared less than 30% homology with the protein database. The gene was
      localized to human chromosome 22q13. RNA dot blot analysis showed that the
      expression level of SNC6 was lower in colorectal cancer than in normal intestinal
      mucosa, and similar results were found in breast cancer. Northern blot showed
      higher expression levels of SNC6 in liver, lung, prostate, testis, ovary and K562
      cell line than in other tissues. CONCLUSION: SNC6 can be further investigated as
      a novel colorectal cancer negatively related gene.

PMID- 9596922
TI  - [The inhibition effect of foreign retinoblastoma gene mediated by recombinant
      adenovirus vector on the growth of smooth muscle cells].
AB  - OBJECTIVE: To study the effect of foreign retinoblastoma (Rb) gene mediated by
      recombinant adenovirus vector on vascular smooth muscle cell (SMC) and the
      possibility by using Rb gene for gene therapy of atherosclerosis and artery
      restenosis. METHODS: Rb gene recombinant adenovirus vector was constructed to
      transfect into rabbits' aortic SMC in vitro. The efficiency of transfection and
      expression was detected by biochemical staining, immunocytochemical analysis and
      polymerase chain reaction technique. The role of Rb gene for SMC proliferation,
      DNA synthesis and cell cycle were observed by cell counting. 3H-incorporation and
      cytometer respectively. RESULTS: Adenovirus vector transfered the Rb gene into
      SMC effectively. The expression of Rb gene restricted the proliferation of SMC,
      decreased the DNA synthesis and plaaied a role in the cell cycle. CONCLUSION: Rb
      gene mediated by adenovirus can be used to treat atherosclerosis.

PMID- 9596924
TI  - [Screening and genetic analysis of fragile X syndrome in Tongling Anhui province
      of China].
AB  - OBJECTIVE: To investigate the prevalence of fragile X syndrome in the Chinese.
      METHODS: Fragile X syndrome was screened from 172,600 people living in Tongling
      city, Anhui province. Suspected patients were tested by PCR and Southern
      Blotting. RESULTS: Seven of 88 mental handicap children were found with fra (X),
      including 3 female and 4 male patients. Six patients, 3 normal transmitting males
      and 5 carriers were found in detailed search in these 6 fra (X) families. Genetic
      linkage analyses of 2 of the families were reported here. CONCLUSION: The
      prevalence of fragile X syndrome in the Chinese is not apparently different from
      the previous reports on the Caucasian population.

PMID- 9596925
TI  - [Impact of nitric oxide on endothelin gene expression in intrapulmonary arteries
      of chronic hypoxic rats].
AB  - OBJECTIVE: To investigate the impact of nitric oxide on endothelin-1 (ET-1) mRNA
      expression in pulmonary artery endothelial cells and pulmonary artery smooth
      muscle cells of chronic hypoxic rats. METHODS: In situ hybridization was
      performed on lung sections from 40 chronic hypoxic rats treated either with L
      Arginine (L-Arg) or N omega-nitro-L-arginine methyl ester (L-NAME) by using cRNA
      probe for ET-1. RESULTS: Most intrapulmonary arteries had 1%-50% of the
      endothelial cells expressing ET-1 mRNA in both one-week and two-week hypoxic rats
      (75% +/- 3% and 71% +/- 6%, respectively), which was significantly inhibited by L
      Arg but augmented by L-NAME administration. Most pulmonary artery smooth muscle
      cells showed no ET-1 mRNA signals in both one-week and two-week hypoxic rats (85%
      +/- 6% and 98% +/- 2%, respectively). However, L-NAME increased ET-1 mRNA
      expression in pulmonary artery smooth muscle cells of hypoxic rats. CONCLUSION:
      Nitric oxide inhibited ET gene expression in both pulmonary artery endothelial
      cells and smooth muscle cells of rats exposed to chronic hypoxia.

PMID- 9596926
TI  - [The effects of hyperinsulinmia and insulin-like growth factor-1 on
      hyperandrogenism in polycystic ovarian syndrome].
AB  - OBJECTIVE: To investigate the effects of insulin (INS) and insulin-like growth
      factor-1 (IGF-1) on ovarian androgen production in women with polycystic ovarian
      syndrome (PCOS). METHOD: 48 patients with PCOS were divided into two groups based
      on body mass index (BMI) (24 were obese BMI > 25 and 24 nonobese) (BMI < 25). 10
      women with normal weight and menstruation were recruited as controls. The serum
      LH, FSH and testosterone (T) levels were determined. 40 cases were measured INS,
      IGF-1, androstenodine (A) and sex hormone binding globulin (SHBG) after a 3-hour
      oral glucose tolerance test (OGTT). Ovarian stroma obtained from 10 patients with
      PCOS and 5 healthy women were cultured in the medium with high INS concentration
      (30 ng/ml and 60 ng/ml). The IGF-1 and A levels were determined. RESULTS: Two
      groups of patients with PCOS demonstrated significant hyperinsulinmia (HI) and
      hyperandrogenism. Significantly higher IGF-1 level was observed in nonobese
      patients (P < 0.01). Insulin markedly stimulated release of IGF-1 (4 times, P <
      0.01) and A (6 times, P < 0.05) in incubation of ovarian stroma obtained from
      PCOS patients. A positive correlation between IGF-1 and A was present in the
      culture medium (r = 0.679, P < 0.05). The serum levels of SHBG were significantly
      lower in PCOS patients. CONCLUSION: The findings suggest that the women with PCOS
      have HI, since INS may play an important role in hyperandrogenism by upregulating
      IGF-1 system in ovary.

PMID- 9596927
TI  - [Quantitative analysis of prevention effect of tetrandrine on pancreatic islet
      beta cells injury in rats].
AB  - OBJECTIVE: To observe the preventive effect of tetrandrine (TET) on pancreatic
      islet beta cells damaged by alloxan in rats with HE, Gomori aldehyde fuchsine
      staining and immunocytochemistry. METHODS: Animal diabetic models were prepared
      with alloxan (50 mg/kg i.v.). Pancreatic islet beta cells density (BD) in the
      section of HRP-SPA immunocytochemistry staining was determined with weibel square
      system. RESULTS: The BD in experimental groups pretreated with TET (100 mg/kg) at
      1.5 hours, 5 hours prior to alloxan injection increased from the control value of
      13 +/- 4 to 62 +/- 9 and 65 +/- 7 (P < 0.001), which had no evident difference
      compared with the BV in normal control group; while the BV (22.5 +/- 7.7) in the
      pretreated group at 7 hours prior to alloxan injection also increased compared
      with the control group. But it was much lower than that in the normal control
      group. When the doses of TET decreased from 100 mg/kg to 50 mg/kg and 25 mg/kg,
      the BD declined from 62 +/- 9 to 45 +/- 5 and 38 +/- 4 (P < 0.01 and P < 0.001).
      CONCLUSION: Tetrandrine can protect islet beta cells a from injury induced by
      alloxan.

PMID- 9596928
TI  - [The inhibitory effect of recombinant human C3 fragment on murine endotoxic
      shock].
AB  - OBJECTIVE: To study the potentially practical use of C3 inactive fragment in anti
      inflammation. METHODS: A vector expressing RGD polypeptide derived from the alpha
      chain segment of human C3 was constructed by using PCR and genetic engineering
      methods and a recombinant protein (namely C 33) was expressed with high
      efficiency in E. coli. RESULTS: The analysis of SDS-PAGE showed the molecular
      weight of C 33 was about 15 KD. Its purity was above 95% after purification. The
      amino acid composition was inconsistent with the theoretical values. U937 cells
      stimulated by low dosage PMA adhered with coated C 33, and the adhesion was
      blocked by anti-CD 11b monoclonal antibody. After injection of purified C 33 into
      mice which were consequently challenged by dead E. coli, the mortality of the
      endotoxic shock was significantly reduced. CONCLUSION: C 33 can specifically bind
      to CD 11b/CD 18. C 33 as a ligand for CD 11b/CD 18 might be potentially used as
      an anti-inflammatory agent.

PMID- 9596929
TI  - [The role of NADPH in the development of neonatal jaundice with G6PD deficiency].
AB  - OBJECTIVE: To investigate the role of NADPH in the development of neonatal
      jaundice with G6PD deficiency. METHODS: The enzyme activities of G6PD, catalse
      (Cat) and glutathione peroxidase (GSH-px) were measured by quantitative
      determination of enzyme activity. The level of MDA was analyzed with alpha
      thiobarbituric acid and the level of NADPH was determined with modified
      Nisselbaum JS's. Comparisons of these markers between G6PD normal and deficient
      erythrocytes were made before and during the incubation of the erythrocytes with
      H2O2. RESULTS: The level of MDA, which was 36 +/- 8n-mol.L-1.gHb-1, was increased
      and that of NADPH, which was 1792 +/- 106mumol.L-1.gHb-1, was decreased in
      jaundiced neonates with G6PD deficiency compared with those with normal G6PD
      activity. When the cells were incubated with H2O2, the level of NADPH and the
      activities of Cat and GSHpx in erythrocytes with normal G6PD activity increased
      at first, and then turned to decrease as the incubation lasted longer than 30
      minutes. But in G6PD-deficient erythrocytes all these markers decreased
      continuously as the cells were incubated with H2O2. CONCLUSIONS: The diminished
      capability of generation of NADPH in G6PD-deficient erythrocytes may contribute
      directly to the more extensive peroxidation of the cells. The defect capacity of
      generation of NADPH, which resulted in the weakened capability of
      antiperoxidation and finally the lysis of erythrocytes, was one of the important
      mechanisms in the development of jaundice in G6PD-deficient neonates.

PMID- 9596930
TI  - [Increased sensitivity to endotoxin and its molecular mechanism after hemorrhagic
      shock].
AB  - OBJECTIVE: To study the increasing sensitivity to endotoxin induced by
      hemorrhagic shock and its mechanism. METHODS: Routine biochemical assay, reverse
      transcription-polymerase chain reaction. (RT-PCR) and cell in situ hybridization
      were used to investigate the effects of low-level endotoxin under hemorrhagic
      shock and its possible mechanism. RESULTS: In rabbits, blood pressure levels were
      significantly decreased, and plasma lactate and beta-glucuronidase (beta-G)
      levels increased in hemorrhagic shock (HS) + LPS group, all of which were
      significantly different from those in the LPS or HS group. All of the animals in
      the HS + LPS group were dead while those in the LPS or HS group survived 24 hours
      after shock. The results of RT-PCR showed that expression of lipopolysaccharide
      binding protein (LBP) mRNA in the liver, lungs and kidneys was increased in rats
      after shock and resuscitation. The expression of CD144 mRNA in the peritoneal
      macrophages in mice was also enhanced after hemorrhagic shock and subsequent
      resuscitation showed by cell in situ hybridization. CONCLUSION: Hemorrhagic shock
      can significantly increase the sensitivity to endotoxin possibly because of up
      regulation of LBP/CD14 after shock.

PMID- 9596931
TI  - [Gastric mucosal hemodynamics of prehepatic portal hypertensive rat model].
AB  - OBJECTIVE: To observe the changes of gastric mucosal hemodynamics and discuss the
      possible regulatory factors of prehepatic portal hypertensive rat. METHOD:
      Prehepatic portal hypertensive (PHT) rat model was produced by various degree of
      portal vein constriction, and gastric mucosal hemodynamics was measured by
      radioactive microsphere technique. Statistical analysis was performed by ANOVA,
      the student t test, and linear correlation. RESULT: The gastric mucosal blood
      flow was significantly reduced in PHT rats, whereas the blood flow in submucosa,
      muscular layer prominently increased. The resistance of mucosal vasculature was
      elevated in PHT rats, however, that of submucosa and muscular layer was decreased
      remarkably. There was a negative correlation between the gastric mucosal blood
      flow and portal pressure. CONCLUSION: The gastric mucosa of prehepatic portal
      hypertensive rat model is poorly perfused prominently. It may be due to the
      increased mucosal vascular resistance and elevated portal pressure.

PMID- 9596932
TI  - [Combined modality prevention and therapy is need to control the spread of
      sexually transmitted diseases].

PMID- 9596933
TI  - [Significant factors of biological therapy in tumors].

PMID- 9596935
TI  - [Polymerase chain reaction in the detection of patients infected by Chlamydia
      trachomatis after treatment].
AB  - OBJECTIVE: To investigate the value of polymerase chain reaction (PCR) for follow
      up patients infected by Chlamydia trachomatis. METHODS: Follow-up specimens were
      collected from 30 patients. Chlamydia trachomatis positive were detected by PCR
      and direct fluorescence assay test (DFA) in the 30 patients before therapy. 15
      patients were treated with minocycline (100 mg twice daily) for 10 days, and 15
      patients were treated with 1.0 g of azithromycine as a single oral dose. RESULTS:
      After 1-2 weeks of antimicrobial therapy, all patients had negative DFA for
      Chlamydia trachomatis, but 9 had positive Chlamydia trachomatis DNA as detected
      by PCR. CONCLUSIONS: The 9 specimens were not confirmed to livae viable organisms
      of Chlamydia trachomatis. The debris of nonviable Chlamydia trachomatis DNA was
      excluded from urinogenital tract at about one month.

PMID- 9596934
TI  - [Risk factor scoring model of STD for pregnant women in antenatal clinic].
AB  - OBJECTIVE: To develop a case finding strategy for STD among pregnant women based
      on risk assessment in China. METHODS: A prospective, random/double blind study of
      the high risk factors for STD in 1,656 pregnant women was conducted from June
      1995 to February 1996. It was carried out at four Guangzhou hospitals on nine
      types of STD, their relative risk factor questionnaire and gynecologic
      examination. RESULTS: The total prevalence of six main STD was 20.89% (346/1656);
      No HIV and syphilis cases were found; The most common disease is cervical
      chlamydial trachomatis at (19.08% 316/1,656). Through statistical calculations
      with COX proportional hazard model, STD symptoms' high risk factors scoring
      system revealed the following: (1) More than one sexual partner in the preceding
      one year; (2) Vulvular lesion vegetation; (3) Dysusia/increased vaginal
      discharge; plus one of the following: 1. unemployed status; 2. sex partner
      unemployed; 3. age (less than 25 years of between 30-34 years of age). These six
      items with "three-three" scoring system can be used as a model to primary
      screening new STD cases using clinical data. Both sensitivity and specificity
      exceeded 60% (61.7% and 67.3% respectively). CONCLUSION: These are significantly
      better than the foreign recommended model and the scoring system in China. It is
      simple, convenient and applicable.

PMID- 9596936
TI  - [Detecting Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium
      in the urogenital tract].
AB  - OBJECTIVE: To epidemiological study of ureaplasma urealyticum (UU), mycoplasma
      hominis (MH) and Mycoplasma genitalium (MG) in the urogenital tract of different
      groups of people. METHOD: Polymerase chain reaction was used. Clinical urogenital
      tract specimens were collected from Beijing, Wuhan and Shantou STD patients and
      different groups of women in Beijing. RESULTS: The positive rates of UU and MH
      were higher than those of MG. In STD high risk group of people, the positive
      rates of mycoplasmas were correlated with the degree of sexual abuse positively.
      The positive rates of UU and MH in none STD high risk group of people could be
      relatively high, especially UU in the pregnant women. CONCLUSIONS: The
      relationship between infection and inhabitant of mycoplasmas in the urogenital
      tract is worthy to be studied further.

PMID- 9596937
TI  - [Molecular cloning and sequence analysis of glycoprotein D gene of herpes simplex
      virus 2 strain Sav and wild strain isolated].
AB  - OBJECTIVE: To study the difference of structure and function of HSV-2 gD gene
      among the wild strain, G and Sav strain. So as to provide theoretical basis for
      future production of HSV-2 vaccine. METHOD: The partial glycoprotein D gene
      sequence of HSV-2 strain Sav and wild strain isolated from recurred genital
      herpes simplex were amplified and cloned with PCR. RESULTS: The homology
      comparison showed that the homology of DNA and amino acid were 99.2% and 99.1%
      respectively. CONCLUSIONS: There are high homology of HSV-2 gD gene among the
      wild strain G and Sav strains, but some variations existed.

PMID- 9596938
TI  - [Expression of Cath-D, P-gp and Her-2 in carcinoma of the cardia].
AB  - OBJECTIVE: To investigate if Cath-D, P-gp and Her-2 are correlated with prognosis
      in patients with cardiac carcinoma. METHODS: Histological sections of 43 patients
      with cardiac cancer were tested by immunohistochemistry and analyzed for
      pathological type and lymphatic metastasis. RESULTS: The research show and that P
      gp and Her-2 were not significant in predicting lymphatic metastasis (P > 0.05),
      but Cath-D positive was significant in lymphatic metastasis (P < 0.01). The P-gp
      and Cath-D were not significant in differential level of cardiac carcinoma and
      expression of Her-2 was significant (P < 0.05). CONCLUSION: The results suggest
      that positive Cath-D is correlated with metastases and positive Her-2 indicates
      poor survival. Special treatment plans for patients with carcinoma of the cardia
      should be designed depending on the above marker tests.

PMID- 9596939
TI  - [Localization and expression of dopamine receptors in stomach and duodenum in
      rats].
AB  - Dopamine is an important neurotransmitter which may contribute to the regulation
      of gastrointestinal function, but its mechanism remains elusive. OBJECTIVE: The
      existence, localization and expression of dopamine receptor mRNAs in rat stomach
      and duodenum were examined by in situ hybridization. METHODS: The oligonucleotide
      probes were selected and synthesized according to the previous work. All the
      probes were labelled with alpha S35dATP using the terminal deoxynucleotide
      transferase, then were hybridized with the frozen, fixed preparation of rat
      stomach and duodenum. The density of silver granules were counted and analyzed by
      the image analysis computer system. RESULTS: It was found that all five subtypes
      of dopamine receptor mRNAs existed in the stomach and duodenum with greatly
      different expression. The distribution of dopamine mRNAs in the stomach were
      mainly localized in the lamina propria near the lamina muscularis mucosae and
      parallel to the longitudinal axis of the tract. Whereas, all five MRNAs were
      spread over the entire layer of the duodenal mucosa. With the image analysis
      system, abundant expressing levels of D5 and D4 mRNAs were documented
      unexpectedly. CONCLUSION: All these results suggest that dopamine produced its
      effect via dopamine receptors especially D5 subtype and D4 receptor might be act
      as a modulator.

PMID- 9596940
TI  - [Metallothionein involvement in the delayed protection after ischemic or anoxic
      preconditioning in myocardium or cultured cardiomyocytes].
AB  - OBJECTIVE: To study whether metallothionein (MT) is an OH scavenger and plays a
      protective role in cardiac ischemic/reperfusion injury. MT involves in the
      delayed protection 24 hr after preconditioning (PC). METHODS: MT contents in
      myocardium or cultured cardiomyocytes are assayed at the 0 hr, 12 hr, and 24 hr
      after PC on the model of rabbit heart in situ or that of the cultured
      cardiomyocytes. The myocardial infarct size, LDH release, cell viability, and the
      content of cellular MDA were measured with or without the intervention of
      PD098059, the inhibitor of mitogen-activated protein kinase in the models before
      PC and different time intervals after PC. RESULTS: The MT contents were increased
      significantly at 2 hr (1406.2 +/- 112.2 vs 129.9 +/- 10.4 pmol/mg Pr., P < 0.01,
      in cardiomyocytes) and 24 hr (1032.7 +/- 199.1 vs 129.9 +/- 10.4 pmol/mg Pr., P <
      0.01, in cardiomyocytes; 62.1 +/- 12.6 vs 27.2 +/- 3.7 pmol/mg Pr., P < 0.01, in
      myocardium) after PC compared with those in normal group. The infarct sizes (13.2
      +/- 3.6% vs 32.3 +/- 5.7%, P < 0.05) and the rise of LDH release in plasma (1944
      +/- 256 vs 2826 +/- 239 IU/L, P < 0.05) were greatly decreased in preconditioned
      myocardium after a long time ischemia-reperfusion than those in the
      unpreconditioned. Compared with the cardiomyocytes unconditioned, the number of
      viable cell (71.0 +/- 1.6 vs 48.2 +/- 2.2%, P < 0.01) was greatly increased, the
      cellular MDA contents (33.5 +/- 12.8 vs 103.5 +/- 15.0 nmol/mg Pr., P < 0.01) and
      the LDH release (850.0 +/- 139.1 vs 1552.0 +/- 102.6 IU/L, P < 0.01) were
      dramatically decreased in preconditioned ones. All the delayed protection at 24
      hr after PC were completely disappeared with the inhibition of MT's production
      with PD098059 (P > 0.05). CONCLUSION: The myocardium or cardiomyocytes at 24 hr
      after PC are offered more capacity to tolerate the I/R damage, and MT involves in
      the delayed protection.

PMID- 9596941
TI  - [Establishment of a novel culture system for specific expansion of human gamma
      delta T cell and study of its biological properties].
AB  - OBJECTIVE: To study the specific expansion method of human gamma delta T cell and
      the molecular mechanism against tumor cells. METHODS: The peripheral blood
      mononuclear cells were co-cultured with XG-7 cells as stimulating cells and
      activated for the expansion of gamma delta T cells. Immunophonotype was analysed
      by IIFA and FACS. The cytotoxicity of gamma delta T cell against tumor cells was
      measured by 51Cr four hour release assay. RESULTS: When this novel culture system
      was used, gamma delta T cells mainly expressing V gamma 9/V delta 2 encoded TCR
      were selected and expanded rapidly from 4.8 +/- 3.4% to 46.2 +/- 8.3%. With
      exogenous interleukin-2, gamma delta T cells were expanded in large quantity
      10(10) within 3 weeks. gamma delta T cells mediated strong cytotoxic activity to
      different tumor cells including K562, Daudi, XG-7 cell lines, but no cytotoxic
      activity to normal cells was observed. XG-7 cells expressed HSP molecules and
      anti-HSP in mAB blocked the proliferation of gamma delta T cells. CONCLUSION: The
      method shows unique biological properties: brief, rapid, well-repeating and wide
      cytotoxic activity against tumor cells. So gamma delta T cells are of value in
      tumor adoptive immunotherapy.

PMID- 9596942
TI  - [Injury effects of nicotine on isolated rat common carotid artery].
AB  - OBJECTIVES: To investigate the injured effects of nicotine on isolated rat common
      carotid artery and to supply experimental proofs for vascular vessel and organ
      transplantation. METHODS: Asins relaxing and contractile functional test of
      isolated vascular vessel and scanning electron microscopy techniques, we observed
      the influence of nicotine on the contractile and the relaxing function of
      isolated artery and the intact of the intima. RESULTS: Lower concentrations of
      nicotine (6 x-10 mol/L-6 x 10(-6) mol/L) produced a concentration-dependent
      constrictor response of 18%-41% relative to those induced by norepinephrine (NE,
      10(-7) mol/L), whereas removal of endothelium reduced nicotine-induced
      constrictions to 5%-21%. Higher concentrations of nicotine (6 x 10(-5) mol/L-6 x
      10(-3) mol/L) not only injured contractile function of vascular smooth muscle but
      also caused severe damage to the intima. Various concentrations of nicotine all
      inhibited acetylcholine-induced relaxation response. CONCLUSIONS: Nicotine not
      only has cytotoxicity to vascular vessel but also results in vasoconstrictor
      effects which depend upon endothelium intact, probably by inhibiting the release
      of endothelium-derived relaxing factor.

PMID- 9596943
TI  - [Chronic diabetic complications and treatments in Chinese diabetic patients].
AB  - OBJECTIVE: To investigate the prevalence of diabetes complications and the
      control of blood glucose, lipids and treatments in Chinese diabetic patients.
      METHODS: In 1994-1996, 626 Chinese diabetics were investigated for their diabetic
      complications, the control of blood glucose, lipids and their treatments by a
      multi-disciplinary team which included diabetic specialists, ophthalmologists,
      neurologists, nephrologists, dieticians, cardiologists, and others. RESULTS: Of
      these patients, 49.6% had hypertension, 46.5% neuropathy, 37.0% retinopathy,
      25.4% ischemic heart disease (including 2.3% with myocardial infarction), 22.8%
      proteinuria (including microalbuminuria), 12.3% cerebral infarction and 1.0%
      amputation. 16% had preproliferative and proliferative retinopathy, and 10.5%
      maculopathy. 28 patients (44 eyes) were blind, but only 29% of them were checked
      by ophthalmologists before this screening. 36% of these patients with
      antihypertensive agents had their blood pressure controlled. 60% patients with
      hypertension were not taking any antihypertensive agent, one-third hypertensive
      patients had their blood pressure uncontrolled even if they had been treated with
      antihypertensive agents. Hyperglycemia was controlled unsatisfactorily in half of
      the patients. Over one-fourth of the patients had severe hyperglycemia. 24%, 48%
      and 59% of the patients had hypercholesterolemia, hypertriglyceridemia and low
      HDL level respectively. 21.9% kept on diabetic diet and about one-fourth had
      their diet uncontrolled, including 14% who had never controlled their diet even
      if their hyperglycemia was severe and 20% newly diagnosed diabetic patients
      untreated. One hundred twenty-seven newly diagnosed patients with duration less
      than 1 month were investigated for their diabetic complications. 19.6%, 17.8% and
      42.5% of them had retinopathy, proteinuria and neuropathy. Eight patients had
      preproliferative and 1 had proliferative retinopathy. Three patients (5 eyes) had
      maculopathy. 33% of these newly diagnosed patients had hypertension, 7 severe
      hypertension, including 3 patients with antihypertensive therapy. CONCLUSIONS:
      Diabetes was found late in the Chinese patients and diabetic complications had
      occurred in some patients by the time the disease was diagnosed. Hypertension was
      common in the Chinese diabetics. Over half of the diabetics had their blood
      glucose and blood pressure uncontrolled. Most of the diabetic patients had not
      controlled their diet. Macrovascular diseases and abnormal lipids metabolism were
      common. The risks of diabetic complications such as smoking, obesity and
      hypertension were not controlled and the awareness of these risks was low in the
      Chinese diabetics.

PMID- 9596944
TI  - [A pathological study of in situ thrombosis of small pulmonary arteries and
      arterioles in autopsy cases of chronic cor pulmonale].
AB  - OBJECTIVE: To study the incidence of thrombosis of small pulmonary arteries and
      arterioles during the exacerbation stage of chronic cor pulmonale. METHODS: 49
      autopsy cases died from the exacerbation of chronic cor pulmonale were chosen as
      the study group, while other 103 autopsy cases without chronic cor pulmonale and
      disseminated intravascular coagulation (DIC) as control group. Morphologic and
      morphometric studies were taken on lung tissues and other organs with focus on
      the thrombi in small pulmonary arteries and arterioles. RESULTS: 44 cases of the
      study group had multiple thrombi in small pulmonary arteries and arterioles, the
      incidence is 89.8%, and in 9 of them, thrombi in proximal pulmonary arteries co
      existed, the incidence is 18.4%, 80% of the thrombi existed in pulmonary
      arteriole. In control group, only 3 cases had thrombi in small pulmonary arteries
      and arteriole, the incidence is 2.9%. All thrombi adhered to endangium, implying
      that they were in situ thrombi. No intravascular thrombosis were found in other
      organs. chi(2) test showed that the incidence of thrombosis and the number of
      thrombi in small pulmonary arteries and arteriole in cases with chronic cor
      pulmonale were significantly higher than that of the control group (P < 0.01).
      CONCLUSIONS: Multiple in situ thrombosis in small pulmonary arteries and
      arterioles is a prominent and common pathological change during the exacerbation
      stage of chronic cor pulmonale. The study suggests a new diagnostic and
      therapeutic concept and provides a morphological and theoretical basis for the
      clinical application of anticoagulants or even the thrombolytic agents for the
      cases of chronic cor pulmonale in the exacerbation stage.

PMID- 9596945
TI  - [The preliminary study on prevention and treatment of neonatal jaundice].
AB  - OBJECTIVE: The purification and identification of heme oxygenase isoforms (HO-1)
      and HO-2 from human liver were described and Sn-protoporphyrin (SnPP) was used to
      inhibit HO-1 activity in order to provide a new method for prevention and
      treatment of neonatal jaundice. METHODS: Human hepatic microsomal fractions were
      purified by DEAE-Sephadex A-25 and hydroxylapatite chromatography. The enzyme
      activities of the two isoforms were detected with and without Snpp. RESULTS: HO-1
      was the predominant form with a ratio of 2.4:1 (HO-1:HO-2). The apparent
      molecular weight of HO-1 and HO-2 on SDS-PAGE was 30,000 and 36,000 under
      reducing conditions, respectively. The study also showed that HO-1 was the
      traditional inducible heme oxygenase and HO-2 was a non-inducible heme oxygenase.
      CONCLUSION: The efficient inhibition effect of SnPP on HO-1 is suggested.

PMID- 9596946
TI  - [Experimental study of selective muscarinic receptor antagonists on attenuation
      of morphine tolerance and dependence in rats].
AB  - OBJECTIVE: To characterize the role of muscarinic receptor subtype in the process
      of the morphine tolerance and dependence. METHODS: The morphine (Antinociception)
      tolerance was assessed by using hot-plate latency, and morphine dependence was
      characterized by naloxone-precipitated withdrawal. Intraperitoneal (i.p.) or
      intrathecal (i.t.) injection of muscarinic M1 selective antagonist pirenzepine or
      M2 selective antagonist methoctramine was carried out. RESULTS: Methoctramine
      (i.p.) for 6 days restored the sensitivity to morphine in male Sprague Dawley
      rats that are tolerant as a result of 6 days of b.i.d. morphine injection, in
      contrast, saline and pirenzepine (i.p.) did not increase the mean HP latency of
      morphine tolerant rats. Both methoctramine and pirenzepine in doses did not alter
      the baseline HP latency. Concurrent treatment with pirenzepine (i.t.)
      significantly attenuated the development of morphine tolerance produced by twice
      daily injection of morphine in a dose-dependent manner, however, methoctramine
      (i.t.) also decreased without dose-relation. In addition, the withdrawal symptoms
      precipitated by naloxone in morphine dependent rats were blocked by methoctramine
      (i.p.) or pirenzepine (i.t.) at single dose injection in a dose-dependent manner.
      Methoctramine (i.t.) at 200 micrograms/kg could partially inhibit the withdrawal
      symptoms. CONCLUSIONS: The data suggested that the muscarinic receptor subtype
      predominating M2 receptor at the peripheral and M11 in the spinal cord mediate
      the process of morphine tolerance and dependence in rat.

PMID- 9596947
TI  - [The role of TNF alpha in the allograft rejection of orthotopic rat liver
      transplantation].
AB  - OBJECTIVES: To measure tumor necrosis factors-alpha (TNF alpha) in rats on the
      3rd, 64d days after orthotopic rat liver transplantation, and detect the
      expression of TNF alpha mRNA in the grafts. METHOD: Reverse transcription
      polymerase chain reaction (RT-PCR) was used. RESULTS: The TNF alpha serum levels
      on postoperative day 3, 6 were significantly higher in allograft group than in
      isogeneic graft group. RT-PCR analysis revealed that TNF alpha mRNA was present
      in allografts, while no TNF alpha mRNA expression occurred in isogeneic grafts.
      Our findings supported that TNF alpha plays an important role in the pathogenesis
      of acute allograft rejection, and suggested that sequential determinations of TNF
      alpha after operation may be of value in the prediction and diagnosis of acute
      rejection.

PMID- 9596948
TI  - [Epidemiologic status of sexually transmitted diseases in China in recent 20
      years].

PMID- 9596949
TI  - [Selection of the therapeutic methods in recurrent patients with primary liver
      cancer in postoperative period].

PMID- 9596950
TI  - [Emphasis on adolescent endocrine diseases].

PMID- 9596951
TI  - [The relationship between TIL from human primary hepatic carcinoma and
      prognosis].
AB  - OBJECTIVE: To determine whether tumor-infiltrating lymphocytes (TIL) could affect
      the prognosis for patients with primary hepatic carcinoma (PHC). METHODS: Tissue
      distribution, proliferative property and cytotoxicity of TIL were measured in
      colour medical image analysis, immunohistochemical technique, 3H-thymidine
      proliferative response and LDH-release assay. RESULTS: On the basis of
      infiltrating level of TIL, all patients with PHC were classified into three types
      in which there can be non-infiltrating, lower infiltrating and high infiltrating.
      The survival time of patients without TIL was shorter than that of patients with
      TIL. In addition, their postoperative intrahepatic recurrences were higher than
      those of the latter. Freshly isolated TIL showed more poor proliferation and
      cytotoxicity than autologous peripheral blood lymphocytes (PBL) in vitro. TIL
      activated with anti-CD3 McAb and rIL-2 displayed higher cytotoxicity against
      fresh autologous hepatic carcinoma cells than against K562 targets. CONCLUSION:
      Clinically, TIL are associated with the prognosis for patients with PHC, however,
      it is in the tumor nest that the functions of TIL are impaired or suppressed by
      some factors locally produced by tumor cells in vivo.

PMID- 9596952
TI  - [Distribution and significance of endothelin-1 and endothelin receptor a mRNA in
      liver after endotoxemia].
AB  - OBJECTIVE: To study the distribution and significance of endothelin-1 (ET-1) and
      endothelin receptor A (ETAR) mRNA in liver after endotoxemia using situ
      hybridization. METHODS: 30 rats were randomized into control and endotoxin
      groups. The endotoxin group was injected with endotoxin at a dose of 10 mg/kg
      body wt. Hybridization of ET-1 and ETAR mRNA of the hepatic tissue was proceeded
      at 3, 6, 12 and 24 hours after endotoxin administration. RESULTS: By in situ
      hybridization, the cell expression of ET-1 mRNA was hepatic sinusoids, the
      endothelial cells of portal vein, and Kupffer cell and the cell expression of
      ETAR mRNA was the small artery smooth muscle cells of hepatic lobule and the
      hepatic sinusoidal lining cells. The accumulation of grain was observed in many
      cells of the liver. The number of accumulating grain increased in unit scope.
      CONCLUSION: ET-1 is synthesized by the hepatic sinusoids, hepatic vascular
      endothelial cells, and Kupffer cells, ETAR may be located on the hepatic vascular
      smooth muscle cells and Ito cells (fat-storing cells) around sinusoid. Endotoxin
      may, on transcription and translation level, lead to the increase of ET-1 and
      ETAR in synthesis and release.

PMID- 9596953
TI  - [Adrenoceptors in the hepatic tissues in cirrhotic rats and cirrhotic patients
      with portal hypertension].
AB  - OBJECTIVE: To study the density of alpha 1-adrenoceptors on hepatic tissues of
      cirrhotic rats and cirrhotic patients with portal hypertension. METHODS: A light
      autoradiography of alpha 1-adrenoreceptors on hepatic tissues of Wistar rats in
      the process of CC1(4)-induced cirrhosis (n = 18) and hepatitis virus B-related
      cirrhotic patients (n = 8) were studied. RESULTS: The density of alpha 1
      adrenoceptors on hepatic tissues (per 10,000 microns2) in rats (normal/cirrhotic
      early stage/cirrhotic middle stage/cirrhotic advanced stage) was 946 +/- 100/431
      +/- 54/567 +/- 92/692 +/- 55 for hepatocytes, 581 +/- 90/250 +/- 87/273 +/-
      92/273 +/- 88 for intrahepatic artery walls, 470 +/- 83/260 +/- 75/258 +/- 77/253
      +/- 83 for intrahepatic portal walls, 362 +/- 92/229 +/- 64/218 +/- 87/212 +/- 90
      for hepatic venule walls and in patients (control human beings/cirrhotic
      patients) it was 1255 +/- 151/583 +/- 48 for hepatocytes, 705 +/- 189/184 +/- 47
      for intrahepatic artery walls 410 +/- 89/ 154 +/- 21 for intrahepatic portal
      walls 339 +/- 95/... ...for hepatic venule walls. CONCLUSION: The density of
      alpha 1-adrenoceptors on various hepatic structures in cirrhotic rats and
      cirrhotic patients are significantly lower than that in normal rats and control
      human beings (P < 0.01).

PMID- 9596954
TI  - [Primary structure and variability of partial sequences in nonstructural gene 5
      region of hepatitis G virus].
AB  - OBJECTIVE: To sequence partial genome of hepatitis G virus (HGV) in the sera of
      patients with different chronic liver disease and paid donors. METHODS: Total
      nucleic acids were extracted from the sera of 3 paid donors, 2 patients with
      liver cirrhosis, and 1 patient with non-A-E chronic hepatitis, then subjected to
      reverse transcriptase-nested-polymerase chain reaction (PCR) with primers derived
      from the putative nonstructural gene 5 (NS5). PCR products were directly
      sequenced after purification. RESULTS: Partial HGV NS5 gene of 6 isolates
      exhibited 87.2% to 93.9% nucleotide sequence identities with 3 reported HGV
      isolates (GBV-C, PNF2161, R10291) while the nucleotide homologies among the 6
      isolates were 90.1% to 93.8%. And 93.6% to 98.7 homolies were found at the
      deduced amino acid level when comparing the 6 isolates with 3 reported ones,
      while 93.61% to 98.40% amino acid identities were found among 6 isolates. In the
      region sequenced, there were 16 conserved proline residues and 8 conserved
      cysteine residues. CONCLUSIONS: Six isolates of HGV were obtained from different
      cases and donors. The partial nucleotide sequences, as well as amino acid
      sequences, of the putative NS5 region of HGV were relatively conserved. This
      region of the genome may be suitable for the development of diagnosis reagents.

PMID- 9596955
TI  - [Relationship between angiotensin 1 converting enzyme gene polymorphism and
      diabetic nephropathy].
AB  - OBJECTIVE: To clarify if ACE gene I/D polymorphism attributes to the development
      of non-insulin dependent diabetes mellitus (NIDDM) and renal complication.
      METHODS: A fragment of 287 bp Alu sequence in inron 16 of ACE gene was used as
      I/D polymorphic marker. After PCR amplification of DNA fragment, 12% non
      denatured polyacrylamide gel electrophoresis was undertaken to analyze the PCR
      products. RESULTS: Allele D was the prominent one (frequency 0.75) in the
      subgroup of DN which was complicated in the earliest stage of NIDDM without HTN,
      CHD and diabetic retinopathy. However, the frequency of allele D was low (0.39)
      in the subgroup of NIDDM without DN, HTN, CHD and diabetic retinopathy, in which
      the duration of each subject was over 5 years. It was significant to compare
      these two mentioned subgroups (P < 0.02, continuity-adjusted X2test, P < 0.05).
      The distribution of genotype in the whole NIDDM group without HTN and CHD (69
      cases) was very similar to the normal control (110 subjects) (I 0.60 to 0.59, D
      0.40 to 0.41). CONCLUSION: The I/D polymorphism of ACE gene may be the factor of
      genetic predisposition of early-onset diabetic nephropathy in Chinese NIDDM.

PMID- 9596956
TI  - [Dobutamine technetium-99m-MIBI spect in evaluating the effects of coronary
      interventional management].
AB  - OBJECTIVE: To evaluate the effects of coronary interventional management by
      dobutamine 99mTc-MIBI single photon emission computed tomography (Dobu-ECT).
      METHODS: Dobu-ECT was performed in pre- and post-interventional management of 32
      patients. Dobutamine was administered intravenously at incremental rates from 5
      to 40 micrograms x kg-1.min-1 at 3-minute intervals. At the highest infusion
      rate, 20 mCi 99mTc-MIBI was injected intravenously, and tomographic imaging was
      performed after one hour. Rest imagings were taken after 24 hours with a second
      dose of 99mTc-MIBI. RESULTS: In 32 patients accepting interventional treatment,
      within 3-6 months follow-up, the results of Dobu-ECT showed a total effectiveness
      rate of treatment was 68.1%. 27 patients of whose Dobu-ECT showed significant
      reversible defects before procedure, the effectiveness rate was 77.8% (21/26), 6
      still had reversible ischemia within the follow-up period, and restenoses of 5
      patients were confirmed by angiography. We also compared the effect of
      percutaneous transluminal coronary angioplasty (PTCA) with intracoronary stenting
      using Dobu-ECT. The results showed that intracoronary stenting was more
      beneficial than PTCA (81.3% vs 43.8%, P < 0.05) CONCLUSION: Dobu-ECT can be used
      to evaluate the effect of interventional management and detect restenosis after
      procedure.

PMID- 9596957
TI  - [Clinical features of hemangioblastomas of the central nervous system].
AB  - OBJECTIVE: To study the clinical features of hemangioblastomas of the central
      nervous system (CNS). METHODS: 174 patients with hemangioblastomas of CNS were
      reviewed from 1982 to 1995. All patients were verified pathologically. RESULTS:
      The tumors occurred mainly in patients between 21 and 40 years of age, and more
      often in men than in women. Most tumors were in the posterior fossa. CT scan of
      119 patients showed that 95 hemangioblastomas appeared as cysts. Magnetic
      resonance imaging (MRI) for 47 patients showed that 32 had cysts. 49 patients
      were examined with angiography or DSA. 164 tumor mural nodules and solid masses
      were completely resected. The subtotal removal of others was performed. These
      patients received radiotherapy. CONCLUSION: Enhanced MRI is the examination of
      choice for preoperative evaluation of cystic hemangioblastomas. Angiography or
      DSA is necessary in the diagnosis of bigger solid masses. The findings suggest
      that patients' age and degrees of section could affect the recurrence of
      hemangioblastoma.

PMID- 9596958
TI  - [Growth regulatory mechanisms of recombinant human interleukin-6 on human lung
      carcinoma cell lines].
AB  - OBJECTIVES: To detect the activity of interleukin-6 (rhIL-6) on human lung cancer
      and the influences of recombinant human IL-6 (rhIL-6) on the in vitro growth of
      high-metastatic human lung giant cell carcinoma cell line PG and low-metastatic
      human lung adenocarcinoma cell line PAa. METHODS: The effects of rhIL-6 on the
      expressions of IL-6, IL-6R, c-myc, c-fos and c-jun mRNAs were analyzed by
      Northern blotting hybridization. RESULTS: rhIL-6 could stimulate the in vitro
      growth of both PG and PAa cells, in a dose-and-time-dependent manner. Both PG and
      PAa cells were shown to express IL-6 and IL-6R identified by reverse
      transcription PCR analysis. Northern blotting hybridization revealed that rhIL-6
      up-regulated mRNA levels of IL-6, IL-6R and c-myc rather than those of c-fos and
      c-jun. CONCLUSION: These data suggest that rhIL-6 may promote the proliferation
      of human lung cancer cell lines PG and PAa, which might, at least partly, be
      related to the up-regulation of expressions of IL-6, IL-6R, c-myc gene
      transcript.

PMID- 9596959
TI  - [Expression of apoptosis regulating proteins P 53, c-myc and bcl-2 on CD34+
      hematopoietic cells isolated from human bone marrow].
AB  - OBJECTIVE: To show the coexpression levels of P 53, c-myc or bcl-2, three key
      apoptosis-regulating proteins on CD34+HC and bone marrow mononuclear cells
      (BMMNC). METHODS: IsolexTM50 or CIMS-100 systems of immunomagnetic bead
      separation and two-dimensional flow cytometric analysis of the immunofluorescence
      double staining were used. RESULTS: With 90%-95% purity of CD34+HC measured by
      FACS, we found that expression levels of P53, c-myc, and bcl-2 on both CD34+HC
      and BMMNC were as follows: CD34+/P53 + 0.1-00.8% versus BMMNC 0.1-0.6%; CD34+/c
      myc+2.4%-11. 3% versus BMMNC 0.1-0.4%; CD34+/bcl-2+0.5-1.6% versus BMMNC 0.1
      0.8%. Coexpression of c-myc and bcl-2 on CD34+HC was significantly higher than
      those observed on BMMNC respectively. CONCLUSION: It could be speculated that
      apoptosis-regulating proteins P53, c-myc and bcl-2 play a key role in the control
      of the survival, proliferation, differentiation, maturation and death in
      hematopoietic cells of physiological state, suggesting that these proteins
      balance the production numbers and quality of hematopoietic cells.

PMID- 9596960
TI  - [Effects of cigarette smoke extract on proliferation and ET-1 release of airway
      smooth muscle cells].
AB  - OBJECTIVE: To investigate whether the effect of smoking on airway smooth muscle
      cells (ASMC) is mediated by the autocrine action of endothelin-1 (ET-1). METHODS:
      Abbit ASMC was cultured exposed to cigarette smoke extract (CSE), we examined the
      mitogenic effect CSE on ASMC in vitro and whether the ETA receptor antagonist JKC
      301 can inhibit this effect. RESULTS: The exposure of ASMC to 10% and 30% CSE
      resulted in obvious cytotoxity. The viability of ASMC was decreased, the lipid
      peroxides (MDA) formation was increased, and the release of lactate dehydrogenase
      (LDH) into supernatant was enhanced. 5% CSE significantly enhanced the cultured
      ASMC[3H]-thymidine (3H-TdR) incorporation by 59.9% (P < 0.01) over control. The
      ASMC proliferative response to 5% CSE was dose-dependently inhibited by JKC-301.
      Moreover, 5% CSE evoked time-dependent release of endogenous ET-1 from ASMC.
      CONCLUSION: These data demonstrate that 5% CSE mediates ASMC proliferation via
      release and autocrine mitogenic action ET-1.

PMID- 9596961
TI  - [Inhibitory effects of two oligosaccharides on murine melanoma experimental
      metastasis].
AB  - OBJECTIVE: To observe the effects of a chemically synthesized tetrose and a
      natural yeast mannan on mouse melanoma experimental liver metastasis. METHODS:
      After treated with 4 mg tetrose (tetrose group) or 4 mg mannan (mannan group) for
      30 minutes at 37 degrees C, 0.5 ml 1 x 10(6)B16-MBK melanoma cells were injected
      intraspleen. 55 days later, melanoma metastasis nodes in the surfaces of the
      liver and other organs as well as mouse survival time were observed. RESULTS: Of
      6 mice in control (B16 cell+PBS), 4 died naturally within 55 days, 2 were
      dissected in the 55th day. All of the 6 mice had metastases in the livers, the
      total number of the melanoma nodes on each liver surface ranged from 2 to 30,
      with the largest one fused to the whole liver. One mouse had a neoplasm in the
      remnant site of injection, 3 had metastases in lungs, while of the 6 mice in the
      tetrose group, one died on the 50th day on injection. In mannan group, all of the
      6 mice survived and no metastasis was seen except the largest diameter of < 1 mm
      of 2 liver nodes in one mouse. Neither tetrose nor mannan group had metastasis of
      the liver, and the weights of liver in the two groups were significantly lower
      than in the control. CONCLUSION: Both tetrose and mannan had the effects in
      blocking melanoma experimental liver metastasis, inhibiting transmigration of the
      liver, and prolonging the survival time of the mouse.

PMID- 9596962
TI  - [Hypoglycemic effects of peroxovanadate complexes on glucose transportor of
      diabetic rats].
AB  - OBJECTIVE: To demonstrate the hypoglycemic effects and translocation of glucose
      transport (Glut 1 and Glut 4) promoted by peroxovanadate and nicotinic acid
      complexes (POR) in streptozotozin-induced diabetic rats. METHODS: Peroxovanadate
      complexes nicotinic acid (POR) was prepared in laboratory. POR and vanadate were
      administered in drink water. The muscles from diabetic rats were subjected to
      sucrose density gradient centrifugation to prepare plasma membrane and microsome
      membrane. Antibodies to COOH-terminal of glucose transportor were used in Western
      Blot to evaluate the translocation. RESULTS: Peroxovanadate complexes of
      nicotinic acid (POR) showed marked hypoglycemic effects on STZ-induced diabetic
      rats. 1mg/kg oral pathway POR could significantly reduce the plasma glucose
      levels (from 18.95 +/- 2.61mmol/L to 6.36 +/- 2.23mmol/L, t = 12.233, P < 0.01)
      over four week's treatment, whereas, same dose of single sodium vanadate or
      nicotinic acid did not have hypoglycemic effects. The net vanadium intake was
      about 1/90 of single effectively vanadate treatment. When Western blot was used
      POR increased the translocation of Glut 4 and Glut 1 from intracellular site of
      plasma membrane. CONCLUSION: Peroxovanadate-nicotinic acid complexes (POR) are
      the novel vanadyl that markedly reduce plasma glucose in a lower dose comparing
      to vanadate in STZ-DM rats by oral administration. Translocation of glucose
      transportor may play a part in hypoglycemic mechanism.

PMID- 9596963
TI  - [Effects of oxidatively modified low density lipoprotein and very low density
      lipoprotein on the expression of MCP-1 in macrophages].
AB  - OBJECTIVE: To examine whether oxidatively modified low density lipoprotein (OX
      VLDL) and very low density lipoprotein (OX-VLDL) induce the expression of MCP-1
      mRNA and protein by rabbit peritoneal exudate macrophages, and to clarify what a
      role of both lipoproteins play in atherogenesis. METHODS: After exposure of the
      macrophages to 25 micrograms/ml of LDL, VLDL, OX-LDL and OX-VLDL respectively,
      and a 24 hour incubation at 37 degrees C, the total RNA was extracted from the
      cells by guanidinium isothiocyanate method, and the media conditioned by the
      cultured macrophages were collected. Meanwhile, MCP-1 protein in the conditioned
      media was determined by using sandwich ELISA. Monocyte migration induced by the
      media was assayed by micropore filter method using modified Boyden chamber.
      RESULTS: After a 24 hour exposure to OX-LDL and OX-VLDL, the MCP-1 mRNA
      expression in macrophages was markedly increased (3.2-fold and 3.4-fold,
      respectively), and the level of MCP-1 protein was also increased (2.2-fold and
      2.5-fold, separately), and furthermore, the monocyte migration distance was
      significantly increased. However, the expression of MCP-1 mRNA and protein was
      only slightly increased when exposed to LDL or VLDL. CONCLUSIONS: Rabbit
      peritoneal exudate macrophages can express MCP-1 mRNA and protein, and OX-LDL and
      OX-VLDL induce stronger MCP-1 mRNA and protein expression in the cells.

PMID- 9596964
TI  - [The effect of interleukin (IL) 12 on hemopoiesis in irradiated mice].
AB  - OBJECTIVE: To investigate the regulating effect of IL-12 on hemopoiesis. METHODS:
      cDNA coding for the two subunits of murine IL-12 were cloned into two different
      eukaryotic expression vectors and transduced into a same NIH3T3 cell line,
      resulting in two engineered fibroblast clones secreting IL-12. Cells were mixed
      with collagens and inoculated into the peritoneal cavities of whole-body
      irradiated mice. RESULTS: On day 10 after treatment, endogenous splenic colony
      forming-unit (CFU-S) counts in mice treated with IL-12-secreting NIH3T3 cells
      were higher than those of mice accepting parental cells or untreated irradiated
      mice. This difference was statistically significant in both 6.0 Gy irradiated
      mice and 7.0 Gy group mice. Histopathological studies showed that NIH3T3-secreted
      IL-12 alleviates the injuries caused by irradiation in both bone marrow and
      spleen, activates hemopoietic cells, increases the number and scale of
      hemopoietic clusters, hence enhancing hemopoietic function including
      erythropoiesis, granulopoiesis, and megakaryocytopoiesis. CONCLUSION: IL-12 up
      regulates and promotes the recovery of hemopoietic function in irradiated mice.

PMID- 9596965
TI  - [Influence of antisense N-ras 1 gene on smooth muscle cell proliferation after
      arterial injury].
AB  - OBJECTIVES: To develop a new way to prevent the process of restenosis after
      arterial injury, we transfered the recombinant antisense N-ras 1 gene to the
      iliac arteries of rabbits after injury and studied the influence of gene therapy
      with antisense N-ras 1 on the vascular segment. METHODS: The constructed
      recombinant antisense N-ras 1 gene to deliver into the iliac arteries of rabbits
      after injury. The rabbits were randomly divided into gene therapy group, vector
      group, and sense N-ras 1 control. The segments of treatment rabbits were analysed
      by angiography of vessels, pathological study, Northern blotting, and Western
      blotting technique. RESULTS: The minimum angiographic lumen diameter measured
      during gene therapy and at follow-up, for the gene therapy group (at 4 weeks) was
      0.80 +/- 0.10mm and the vector control 0.35 +/- 0.13mm (P < 0.01).
      Histologically, the area of neointima measured, for gene the therapy group (at 4
      weeks) was 0.43 +/- 0.05mm2, and the vector control group 0.82 +/- 0.03mm2 (P <
      0.01). By using Northern blotting and Western blotting technique, we found that
      cell's ras mRNA of the vessel segments of gene local delivery was significantly
      lower than that of the control. Cell's p21 was significantly lower than that of
      the control. CONCLUSIONS: The antisense N-ras 1 inhibites VSMC proliferation. The
      result implicates the potential value in future gene therapy of restenosis.

PMID- 9596966
TI  - [Progress in the study of von Hippel-Lindau syndrome].

PMID- 9596968
TI  - [Problems in the development of organ transplantation in China].

PMID- 9596967
TI  - [Psychosomatic health in adolescents].

PMID- 9596969
TI  - [Sex education in 6th and 7th grade girls].
AB  - OBJECTIVES: To help the students to know the basic knowledge on sexual health of
      adolescent, to have a positive attitude toward the phenomenon occurred during the
      adolescence; and to promote the health behaviors of girls. METHODS: Three hundred
      and sixty-three 6th and 7th grade girls from Fuxin city were involved. These
      girls were divided into experimental group and control by class. Pretest, post
      test one month after education, and follow-up test four months after education
      were conducted respectively. RESULTS: After education, the score of basic
      knowledge on sexual health of the girls in the experimental group increased from
      4.86 to 17.20. The score of positive attitude toward menstruation increased from
      31.8 to 42.3. The percentage of the girls who had healthful and optimistic
      emotion during the menstruation increased from 43.5% to 82.9%. The percentage of
      the girls who visited hospital if they had reproductive diseases increased from
      54.3% to 87.6%. The percentage of the girls who often wash the external genitals
      during menstruation increased from 50.9% to 79.0%. The ability of avoiding sexual
      harassment and abuse was enhanced. The follow-up test showed that the effects of
      sex education lasted. During the whole experimental process, no student who had
      sexual intercourse was discovered. CONCLUSION: Sex education in 6th and 7th grade
      girls is essential, feasible and effective in China.

PMID- 9596970
TI  - [Epidemiological study of external genital diseases in 5172 adolescents].
AB  - OBJECTIVE: To study the incidence of external genital diseases and the health
      status of external genitalia in male adolescents in china. METHODS: 5172 male
      adolescents aged 7-22 were sampled randomly to examine the diseases and health
      status of external genitalia. According to the diagnostic criteria in textbook
      Surgery (3rd edition), all examinations were carried out by urologists. RESULTS:
      The total incidence of redundant prepuce was 67.79%, phimosis 10.09%, varicocele
      19.82%, hydrocele 0.87%, concealed penis 0.68%, cryptorchidism 0.39%. CONCLUSION:
      The health status of external genitalia in male adolescents is bad. Redundant
      prepuce and phimosis are common diseases. The examination of external genitalia
      should be carried out in the physical examination of admission. This study may
      provide the theoretical evidence for prevention and treatment of male external
      genital disease as well as the important data for study on andrology.

PMID- 9596971
TI  - [Follow-up study on children with obesity and hypertension].
AB  - OBJECTIVE: To study obesity development and its relationship between obesity and
      hypertension of children in China. METHOD: A 8-year follow-up study was conducted
      in 468 children aged 6 years by the criteria of hight, weight, thickness of skin
      fat and blood pressure. RESULTS: Obesity morbidity rose from 6 years (4.9%) to 13
      years (16.2%), with the peak at 9 to 11 years. Both sexes developed obesity,
      which dominated in males. Children with obesity developed hypertension at age 13,
      the morbidity increased 3.5 times than that of those without obesity. CONCLUSION:
      Prevention of malnutrition is important in China but interventions to children
      with obesity in China are in urgent need.

PMID- 9596972
TI  - [Investigation of understanding and willingness of organ transplantation in young
      people in Beijing, Shanghai, Wuhan].
AB  - OBJECTIVE: To understand the knowledge of young people in cities in China about
      organ transplantation and their willingness to donate organs, methods of
      donation, and the willingness of donators. METHODS: A questionnaire was designed
      in investigating 3,012 young people (999 questionnaires in Beijing, 990 in
      Shanghai, 1,023 in Wuhan) aged 20-45 years in the three cities. The data were
      processed by SPSS software. RESULTS: Over 90% of the people investigated knew
      that human organs can be transplanted 85% considered organ transplantation is a
      warefare undertaking. 85% thought organ transplantation is necessary when
      someone's organ is severely-impaired. If possible, 70% were willing to receive
      organ transplantation. With regard to forms of donation, over 70% emphasized the
      individual willingness combined with reimbursement. The Preferred recipient in
      sequence were relatives, special institutions, friends, volunteers, and others.
      The various factors. affecting understanding of organ transplantation were
      analysed. CONCLUSION: In cities of China, young people have a better
      understanding of organ transplantation, but conventional attitudes and feudal
      habits are the major obstacle to the development of organ transplantation in
      China.

PMID- 9596973
TI  - [HLA-DR typing by standard serology and PCR-amplification with sequence-specific
      primers: a comparative study].
AB  - OBJECTIVE: DNA typing for HLA-DR by polymerase chain reaction with sequence
      specific primers (PCR-SSP) compared with standard serology to evaluate the
      reliability and clinical practicability. METHODS: Double-blind typing for HLA-DR
      alleles was carried out using DNA typing by PCR-SSP and standard serology by
      microlymphocytotoxicity technique in 61 donors and 101 recipients of cadaveric
      transplantation. Matching time, sensitivity, specificity and clinical
      practicability were compared according to typing results by both methods.
      RESULTS: All 162 samples were able to be typed by PCR-SSP. A total of 308 alleles
      were detected (16 DR "blank"). The results of matching were confirmed by analysis
      with restriction endonucleases and Southern hybridization. The specificity and
      reproducibility were 100%. HLA-DR typing was performed in 5 hours by PCR-SSP or
      20 hours by serology. The discrepancy rate between PCR-SSP and serological HLA-DR
      typing was 30.2% (35.6% for kidney recipients, 21.3% for donors). The
      discrepancies consisted of 8 loci being doubtful, 29 antigens being incorrectly
      interpreted by serology and 20 of serological "blanks" turning out to be
      definable alleles by the DNA method. CONCLUSIONS: Genotyping for HLA-DR by PCR
      SSP offers the advantages of better reagent and sample availability, more rapid
      and greater accuracy, all of which would warrant that this approach was suitable
      for clinical practice in organ transplantation.

PMID- 9596974
TI  - [Potential role of gut peptides in stress-induced colonic motor disorder].
AB  - OBJECTIVE: To explore the potential role of gut peptide in stress-induced colonic
      motor disorder. METHODS: In 9 conscious Wistar rats pre-equipped with strain
      gauge transducers on ascending and descending colon, colonic motility was
      recorded before, during and after stress. And colonic transit was evaluated by
      instilling Cr into the cecum through chronically implanted cannula in each group
      of 16 rats with or without stress, and then calculating the geometric center (GC)
      of radioactivity. The contents of VIP, SP, NT, SST, MOT and Leu-ENK in plasma,
      colonic mucosa and muscle layer were assessed in 16 stressed and 16 control rats.
      Exogenous peptides (VIP, SP, SST, NT) were intravenously administered in 9 rats
      to determine the colonic motor response. Also, the effects of peptides on colonic
      circular muscle strips were investigated. RESULTS: Motor activity was increased
      after stress, whereas colonic transit was delayed. In the stressed rats, plasma
      levels of VIP and Leu-ENK were higher than those in controls. The content of Leu
      ENK in muscle tissue decreased. Both in vivo and in vitro studies showed that SP
      and NT excited, whereas VIP and SST inhibited colonic motor activity. CONCLUSION:
      Release of certain peptides is altered by stress. Increased release of ENK and
      VIP may be involved in stress-induced colonic motor disorder and in the
      regulation of "stress hormone" release.

PMID- 9596975
TI  - [Preclinical studies on thymidine kinase gene (TK) and gancyclovir system for
      treatment of malignant astrocytoma].
AB  - OBJECTIVE: To study preclinically TK gene mediated GCV system for treatment of
      human malignant astrocytoma. METHODS: The TK gene (TKc) was isolated from a
      Chinese strain of HSV-1 (17) and sequenced. A retroviral vector with TKc
      (pLTKcSN) and its package cell line (pLTKcSN/VPC) were constructed. The in vitro
      assay for its activity was performed by mixed cultures of TK producer cells and
      rat glioma C6 cells after treatment with GCV. The in vivo efficacy was examined
      by in situ inoculation of virus-producer cells after intracerebral implantation
      of C6 cells. Safety tests were analyzed by inoculation of pLTKcSN/VPC and
      injection of GCV, in mouse, rat, and Rhesus monkey, evaluated by
      histopathological examination and in situ hybridization with TK probe. RESULTS:
      TKc gene contained 5 nucleotide difference covering 2 amino acid variation. The
      retroviral vector pLTKcSN and its producer cell pLTKcSN/VPC (with a titer at 0.5
      1.0 x 10(6) CFU/ml) can efficiently mediate cytotoxicity of GCV to C6 cells, both
      in vitro and in vivo. The above system had no serious adverse effect and
      remarkable or irreversible pathological changes in 48 mice, 24 rats and 6 Rhesus
      monkeys. CONCLUSION: The preclinical studies indicated that it would be effective
      and safe for clinical trial after approval.

PMID- 9596976
TI  - [In vivo induction of antitumor immune response by tumor cells fused with GM-CSF
      gene-modified dendritic cells].
AB  - OBJECTIVE: To investigate the induction of antitumor immune response and
      therapeutic effects of the vaccination with the fused cells between tumor cells
      and GM-CSF gene -modified dendritic cells. METHODS: The dendritic cells were
      isolated from the spleens of C57BL/6 mice, infected with GM-CSF adenovirus, and
      then fused with B16 murine melanoma cells. The positive fused cells were enriched
      by magnetic cell sorting with anti-Ia antibody and adherent culture. The
      protective and therapeutic effects of the vaccination with the fused cells were
      investigated. RESULTS: Vaccination with the inactivated fused cells induced more
      potent CTL activity against parental B16.F10 cells, and led to the resistance
      against the rechallenge of alive parental B16.F10 cells. After treatment with the
      inactivatedly fused cells, the survival time of the tumor-bearing was mice
      greatly extended and the metastatic tumor nodules on the pulmonary surfaces
      reduced. CONCLUSIONS: Vaccination with the fused cells between tumor cells and
      dendritic cells could elicit potent antitumor responses, and combined with GM-CSF
      gene transfection, more potent results can be achieved.

PMID- 9596977
TI  - [GSH.Px or SOD encapsulated erythrocytes in the study of cerebral ischemia
      reperfusion].
AB  - OBJECTIVE: To study the practicability of using red blood cells (RBC) as the
      carrier of SOD or GSH.Px and to observe the effects of RBC-SOD and RBC-GSH.Px on
      cerebral ischemia-reperfusion (I-R). METHODS: The method of hypotonic dialysis
      was used in encapsulating SOD or GSH.Px into rabbit RBC. The circulation half
      lives (T1/2) of RBC-SOD and RBC-GSH.Px were determined in rabbits by 51Cr
      radiolabel. Lipid peroxidation (LPO) and nitric oxide (NO) in plasma and TTC
      staining of cerebrum were examined. RESULTS: T1/2 was 13.4 +/- 1.5 days (n = 6)
      for RBC, 13.7 +/- 1.0 days (n = 5) for RBC-SOD, and 7.3 +/- 2.5 days (n = 5) for
      RBC-GSH.Px. The concentration of NO reduced gradually as reperfusion continuing
      in control group, but it was a state of significant increase in NO concentration
      during the 4.5 hours of reperfusion, in RBC-SOD group. The increase of NO was
      inhibited by the administration of RBC-GSH.Px or (RBC-SOD + RBC-GSH.Px). The
      increase of LPO during cerebral I-R was inhibited by RBC-SOD or (RBC-SOD + RBC
      GSH.Px). Staining with TTC showed that the RBC-SOD, RBC-GSH.Px and (RBC-SOD + RBC
      GSH.Px) could effectively protect cerebrum For I-R damage, especially the last
      one. CONCLUSION: Using RBC as the carrier of SOD or GSH.Px is practicable. Intact
      RBC-SOD and RBC-GSH.Px could scavenge active oxygen produced during cerebral I-R.

PMID- 9596978
TI  - [Radionuclide scintigraphy in etiologic diagnosis of gastrointestinal bleeding in
      children].
AB  - OBJECTIVE: To assess the role of radionuclide scintigraphy in etiologic diagnosis
      of gastrointestinal bleeding in children, especially in detecting the cases of
      Meckel's diverticulum or double intestine. METHODS: 99mTc-pertechnetate abdominal
      scintigraphy was undertaken in 26 children with history of gastrointestinal
      bleeding. Additional 99mTc-RBC scintigraphy was performed in 12 cases who gave a
      negative 99mTc-pertechnetate scintigraphy as they had the signs of active
      bleeding. The final diagnosis of all cases was proved by surgery and pathology or
      endoscopy. RESULTS: In detecting Meckel's diverticulum and double intestine, the
      sensitivity, specificity and accuracy of 99mTc-Pertechnetate scintigraphy were
      85. 7% (12/14), 91.7% (11/12) and 88.5% (23/26) respectively. CONCLUSION:
      Radionuclide scintigraphy may be the first procedure to explore the etiology in
      the lower digestive tract.

PMID- 9596979
TI  - [Blocking action of tetrandrine on the cell proliferation induced by PDGF in
      human lung fibroblasts and liver Ito cell of rats].
AB  - OBJECTIVE: To investigate the mechanism of hepatic fiberosis, the effects of
      platelet-derived growth factor (PDGF) on cell proliferation activity and collagen
      synthesis in human lung fibroblasts (HLF) and Ito cells of rat liver as well as
      the blocking action of tetrandrine on the cell proliferation induced by PDGF.
      METHODS: The Ito cells were separated from liver of rats by using the perfusion
      of collagenase and density pradient centrifugation. The cell proliferation was
      observed with the incorporation method of H-TdR and 3H-L-proline. RESULTS: Under
      condition of cell culture with 1% serum, PDGF could significantly enhance DNA
      synthesis, cell proliferation and collagen synthesis, which increased in degree
      with a rising of concentration of PDGF. This occurred in culture without serum,
      but under the same condition, if PDGF was applied together with insulin-like
      growth factor (IGF), it enhanced cell proliferation. The result also showed that
      the dose of tetrandrine below the level of inhibiting cell DNA synthesis could
      antagonize the stimulation action of PDGF on cell proliferation and collagen
      synthesis. CONCLUSION: Tetrandrine plays the blocking action in the promoting
      cell proliferation induced by PDGF.

PMID- 9596980
TI  - [The effect of systemic and local irradiation on wound macrophages and the repair
      promoting action of phenytoin sodium].
AB  - OBJECTIVE: To study the effect of systemic and local irradiation on wound
      macrophages (M phi) and the pair promoting action of phenytoin sodium on
      irradiation-impaired wound healing. METHODS: Wound M phi was collected by
      polyvinyl alcohol sponges which were implanted in a rat dorsum incision. The
      number of M phi, phagocytic function of wound M phi, and the release of tumor
      necrosis factor (TNT alpha) and interleukin-1 (IL-1) from wound M phi, and wound
      breaking strength (WBS) were respectively investigated. RESULTS: WBS was deceased
      after 6Gy systemic irradiation and 20Gy local irradiation, and phenytoin sodium
      improved WBS in normal wound and radiation-impaired wound. After 6Gy systemic
      irradiation the phagocytic function of wound M phi, the release of TNF alpha and
      IL-1 from wound M phi, as well as the number of M phi in wound, were
      significantly decreased on days 3, 5, 8 after wounding. After 20Gy local
      irradiation, the ratio of M phi in wound cells was significantly decreased on
      days 3, 5, 8, 13 after wounding, but the function of macrophage was not
      significantly decreased. Phenytoin sodium significantly increased the number of
      wound M phi, improved the phagocytic function of M phi, and the release of TNF
      alpha and IL-I from wound M phi on days 3, 5, 8 days after wounding despite the
      rats were radiated or not. CONCLUSION: The results indicated that the decrease of
      number and function of wound M phi play an important role in the impairment of
      early wound healing by systemic irradiation. Phenytoin sodium accelerated normal
      and irradiation-impaired wound healing by increasing the number of wound M phi
      and improving the M phi function.

PMID- 9596981
TI  - [Improvement of the pre-hypertensive inherited cardiac dearangements with
      phenylalanine in essential hypertension].
AB  - OBJECTIVE: To assess whether phenylalanine intervention can effectively improve
      the pre-hypertensive inherited cardiac hypertrophy and systolic dysfunction in
      young offsprings of patients with essential hypertension (ER). METHODS: Ninty-six
      normotensive adolescents with hypertensive family history and associated with
      inherited cardiac hypertrophy, i.e, interventricular, septum (IVST) and (or) left
      ventricular post wall thickness (PWT) > or = 10.5 mm, were screened according to
      the normal range criteria of ultrasonic-cardiogram (UCG) obtained previously from
      50 normotensive adolescents without hypertensive genetic predisposition. The UCG
      parameters before and after 3, 6, 9 months of observation were compared between
      intervention group (Phe 1 g/d 58 subjects) and placebo-control group (placebo 1
      g/d, 38 subjects) in 2 separate trials by a double-blind, randomized, cross-over
      and comparable placebo-control design. RESULTS: The hypertrophy and dilatation of
      ascending aorta and left heart structure were regressed after intervention, i.g,
      the changes after 9 months intervention, IVST dropped from 10.9 +/- 1.2 to 9.2 +/
      0.6 mm, PWT from 9.5 +/- 1.0 to 8.6 +/- 0.6 mm, left ventricular mass index from
      92 +/- 15 to 70 +/- 11 g/m2; All of the parameters reflecting the systolic
      function of left ventricle were improved in pooled group of 2 trials. The UCGs
      after placebo was fundamentally not changed except some sporadic values. The
      results were similar in 2 separate trials. The improvement after Phe and its
      return towards that of pre-intervention after stope were remarked at 6 months.
      CONCLUSION: The inherited cardiac dearrangement seen in adolescents with
      hypertensive genetic predisposition can be assumed to be the pre-hypertensive
      changes of EH. It can be reversed by phenylalanine--a natural and essential amino
      acid.

PMID- 9596982
TI  - [Uses of three-dimensional ultrasonography in obstetrics and gynecology].

PMID- 9596983
TI  - [Advances in the study of nephrology in China in 1996].

PMID- 9596984
TI  - [Advances in the study of genetics in China in 1996].

PMID- 9596985
TI  - [Advances in the study of pharmacogenetics in China in 1996].

PMID- 9596986
TI  - [Advances in the study of microcirculation in China in 1996].

PMID- 9596987
TI  - [Advances in the study of hyperbaric oxygenation in China in 1996].

PMID- 9596988
TI  - The biological and functional significance of the sperm acrosome and acrosomal
      enzymes in mammalian fertilization.
AB  - The mammalian spermatozoon undergoes continuous modifications during
      spermatogenesis, maturation in the epididymis, and capacitation in the female
      reproductive tract. Only the capacitated spermatozoa are capable of binding the
      zona-intact egg and undergoing the acrosome reaction. The fertilization process
      is a net result of multiple molecular events which enable ejaculated spermatozoa
      to recognize and bind to the egg's extracellular coat, the zona pellucida (ZP).
      Sperm-egg interaction is a species-specific event which is initiated by the
      recognition and binding of complementary molecule(s) present on sperm plasma
      membrane (receptor) and the surface of the ZP (ligand). This is a carbohydrate
      mediated event which initiates a signal transduction cascade resulting in the
      exocytosis of acrosomal contents. This step is believed to be a prerequisite
      which enables the acrosome reacted spermatozoa to penetrate the ZP and fertilize
      the egg. This review focuses on the formation and contents of the sperm acrosome
      as well as the mechanisms underlying the induction of the acrosome reaction.
      Special emphasis has been laid on the synthesis, processing, substrate
      specificity, and mechanism of action of the acid glycohydrolases present within
      the acrosome. The hydrolytic action of glycohydrolases and proteases released at
      the site of sperm-zona binding, along with the enhanced thrust generated by the
      hyperactivated beat pattern of the bound spermatozoon, are important factors
      regulating the penetration of ZP. We have discussed the most recent studies which
      have attempted to explain signal transduction pathways leading to the acrosomal
      exocytosis.

PMID- 9596989
TI  - Caspase activation is an early event in anthracycline-induced apoptosis and
      allows detection of apoptotic cells before they are ingested by phagocytes.
AB  - An increasing number of methods are being described to detect apoptotic cells.
      However, attempts to detect apoptotic cells in clinical samples are rarely
      successful. A hypothesis is that apoptotic cells are cleared from the circulation
      by phagocytosis before they become detectable by conventional morphological or
      cytometric methods. Using LR73 adhering cells as phagocytes in a model of in
      vitro phagocytosis, we found that phagocytosis of daunorubicin (DNR)-treated
      U937, HL60, or K562 leukemia cell lines occurred prior to phosphatidylserine
      externalization, DNA hydrolysis, chromatin condensation, nuclear fragmentation,
      or mitochondrial potential alteration. Moreover DNR-treated K562 cells were
      eliminated by phagocytes while apoptosis was never observed by any of the above
      methods. By contrast, using a fluorometric batch analysis assay to detect caspase
      activity in ceramide- or DNR-treated cells (fluorogenic substrate for caspase),
      we found that caspase activity increased in apoptosis-committed cells before they
      were detected by flow cytometry or recognized by phagocytes. Similarly a caspase
      activity increase was detected in circulating mononuclear cells of luekemic
      patients 15 h after the beginning of anthracyclin treatment. We suggest that
      recent findings on enzymatic events (caspase activation) occurring in the early
      events of apoptosis must now allow the development of new markers for apoptosis,
      irrespective of the morphological features or internucleosomal fragmentation
      which are late events in apoptosis.

PMID- 9596991
TI  - Evidence against a looped structure of the inactive human X-chromosome territory.
AB  - Multicolor fluorescence in situ hybridization with a whole chromosome composite
      probe for the X-chromosome and microdissection probes for the Xp and Xq arms, as
      well as for the Xp terminal, Xq terminal, and X centromer specific subregional
      probes, was applied to three-dimensional (3D) preserved human female amniotic
      fluid cell nuclei. Confocal laser scanning microscopy and three-dimensional image
      analysis demonstrated distinctly separated Xp arm and Xq arm domains. 3D distance
      measurements revealed a high variability of intrachromosomal distances between
      Xpter, Xcen, and Xqter specific probes within both X territories. A 3D distance
      measurement error of +/- 70 nm was found in control experiments using quartz
      glass microspheres labeled with different fluorochromes. Our data argue against
      the hypothesis of Walker et al. (1991, Proc. Natl. Acad. Sci. USA 88, 6191-6195)
      that a looped structure of the inactive X territory is formed by tight telomere
      telomere associations.

PMID- 9596990
TI  - Occurrence of proteinaceous 10-nm filaments throughout the cytoplasm of algae of
      the order Dasycladales.
AB  - Previously, whole-mount electron microscopy of nuclei extruded together with
      residual cytoplasm from the rhizoids of several algal species of the order
      Dasycladales has revealed the occurrence of an intra- and perinuclear network of
      10-nm filaments morphologically indistinguishable from that of mammalian vimentin
      intermediate filaments. The present investigation demonstrates the existence of a
      filament system throughout the cytoplasm of the rhizoid, stalk, and apical tip of
      these giant cells. However, while the perinuclear 10-nm filaments interconnecting
      the nuclear surface with a perinuclear layer of large, electron-dense bodies
      filled with nucleoprotein material are of smooth appearance, those continuing
      within and beyond the perinuclear bodies are densely covered with differently
      sized, globular structures and, therefore, are of a very rough appearance. The
      filaments in the very apical tip of the cells are mainly of the smooth type. The
      transition from smooth to rough filaments seems to occur in the numerous
      perinuclear dense bodies surrounding the large nucleus. Digestion of the rough
      filaments with proteinase K removes the globules from the filament surface,
      revealing that throughout the nonvacuolar, intracellular space the filaments have
      the same basic 10-nm structure. On the other hand, gold-conjugated RNase A
      strongly binds to the filament-attached globules but not to the smooth,
      perinuclear, and the proteinase K-treated, rough filaments. In addition, an
      antibody raised against Xp54, a highly conserved protein which in Xenopus oocytes
      is an integral component of stored mRNP particles, decorates the rough but not
      the smooth 10-nm filaments. These results support the notion that the 10-nm
      filament system of Dasycladales cells plays a role in the transient storage of
      ribonucleoprotein particles in the cytoplasm and possibly fulfils a supportive
      function in the actomyosin-based transport of such material to various
      cytological destinations.

PMID- 9596992
TI  - Induction of endothelial cell apoptosis by solid tumor cells.
AB  - The mechanisms by which tumor cells extravasate to form metastasis remain
      controversial. Previous studies performed in vivo and in vitro demonstrate that
      the contact between tumor cells and the vascular wall impairs endothelium
      integrity. Here, we investigated the effect of breast adenocarcinoma MCF-7 cells
      on the apoptosis of human umbilical vein endothelial cells (HUVEC). TUNEL
      labeling, nuclear morphology, and DNA electrophoresis indicated that MCF-7 cells
      induced a two- to fourfold increase in HUVEC apoptosis. Caspase-3 activity was
      significantly enhanced. Neither normal cells tested (mammary epithelial cells,
      fibroblasts, leukocytes) nor transformed hematopoietic cells tested (HL60,
      Jurkat) induced HUVEC apoptosis. On the contrary, cells derived from solid tumors
      (breast adenocarcinoma, MDA-MB-231 and T47D; fibrosarcoma, HT 1080) had an effect
      similar to that of MCF-7 cells. The induction of apoptosis requires cell-to-cell
      contact, since it could not be reproduced by media conditioned by MCF-7 cells
      cultured alone or cocultured with HUVEC. Our results suggest that cells derived
      from solid tumors may alter the endothelium integrity by inducing endothelial
      cell apoptosis. On the contrary, normal or malignant leukocytes appear to
      extravasate by distinct mechanisms and do not damage the endothelium. Our data
      may lead to a better understanding of the steps involved in tumor cell
      extravasation.

PMID- 9596993
TI  - The apoptotic and nonapoptotic nature of the terminal differentiation of
      erythroid cells.
AB  - The morphology of erythroid cells changes dramatically during the course of their
      terminal differentiation. According to calculations made with cytospin
      preparations obtained from Syrian hamster yolk-sac-derived erythroid cells, the
      area of nuclei at day 10 of gestation ranges from 25 to 85 micron 2 and is
      reduced to 15-25 micron 2 on day 13 [K. Morioka and R. Minamikawa-Tachino, Dev.
      Growth Differ. 35, 569-582, 1993]. The DNA and protein contents of each nucleus
      also decrease during this period. Nonspecific fragmentation of DNA was detected
      by agarose gel electrophoresis in all samples obtained from day 10 to day 13 of
      gestation, while distinct ladders of DNA fragments were not detected. DNA
      fragmentation was also detected by an in situ DNA-end labeling (TUNEL) assay. As
      the terminal differentiation proceeded, gradual decreases in levels of both
      histone H1 and most nonhistone proteins were observed by SDS-polyacrylamide gel
      electrophoresis, while levels of core histones appeared to be constant. In
      particular, lamin B2 was almost completely lost from the nuclear matrix fraction
      on day 11. These results suggest that the terminal differentiation of erythroid
      cells and apoptosis might have common mechanisms. However, expansion of the
      cytoplasm during the terminal differentiation distinguishes these processes. In
      addition, in the erythroid terminal differentiation, nuclei never form lobules or
      become fragmented; no apoptotic bodies are formed, occurrence of the apoptosis
      like cellular change is not sporadic but rather synchronous, and the process is
      slow, with at least several days being required for cell death. These
      characteristics are different from those of typical apoptosis. Thus, the terminal
      differentiation of nucleated embryonic erythroid cells exhibits both apoptotic
      and nonapoptotic features.

PMID- 9596994
TI  - CaMK-II inhibition reduces cyclin D1 levels and enhances the association of
      p27kip1 with Cdk2 to cause G1 arrest in NIH 3T3 cells.
AB  - The calmodulin-dependent protein kinase-II (CaMK-II) inhibitor KN-93 has been
      shown to reversibly arrest mouse and human cells in the G1 phase of the cell
      cycle [Tombes, R. M., Westin, E., Grant. S., and Krystal, G. (1995) Cell Growth
      Differ. 6, 1073-1070; Rasmussen, G., and Rasmussen, C. (1995) Biochem. Cell Biol.
      71, 201-207]. The stimulation of Ca(2+)-independent (autonomous) CaMK-II
      enzymatic activity, a barometer of in situ activated CaMK-II, was prevented by
      the same KN-93 concentrations that cause G1 phase arrest. KN-93 caused the
      retinoblastoma protein pRB to become dephosphorylated and the activity of both
      cdk2 and cdk4, two potential pRb kinases, to decrease. Neither the activity of
      p42MAP kinase, an early response G1 signaling molecule, nor the phosphorylation
      status or DNA-binding capability of the transcription factors serum response
      factor and cAMP responsive element-binding protein was altered during this G1
      arrest. The protein levels of cyclin-dependent kinase 2 (cdk2) and cdk4 were
      unaffected during this G1 arrest and the total cellular levels of the cdk
      inhibitors p21cip1 and p27kip1 were not increased. Instead, the cdk4 activity
      decreases resulting from KN-93 were the result of a 75% decrease in cyclin D1
      levels. In contrast, cyclin A and E levels were relatively constant. Cdk2
      activity decreases were primarily the result of enhanced p27kip1 association with
      cdk2/cyclin E. All of these phenomena were unaffected by KN-93's inactive analog,
      KN-92, and were reversible upon KN-93 washout. The kinetics of recovery from cell
      cycle arrest were similar to those reported for other G1 phase blockers. These
      results suggest a mechanism by which G1 Ca2+ signals could be linked via
      calmodulin-dependent phosphorylations to the cell cycle-controlling machinery
      through cyclins and cdk inhibitors.

PMID- 9596996
TI  - Elevated expression of the cdc25A protein phosphatase in colon cancer.
AB  - The nuclear protein phosphatase cdc25A has been postulated to be a protooncogene.
      The total nuclear phosphotyrosyl protein phosphatase (PTP) activity and the
      expression of cdc25A were compared in normal and cancerous colon epithelial
      tissue. Nuclei derived from normal mucosal epithelium and tumors were analyzed
      for phosphotyrosyl protein phosphatase activity using the malachite green assay
      and a synthetic phosphotyrosyl peptide based on the sequence of cdc2, a known
      cdc25A phosphotyrosyl protein substrate. Tumorigenesis resulted in elevated
      nuclear PTP activity (343.0 +/- 37.0% of normal epithelial PTP activity) in 52%
      (29 of 56) of colon tumors. In all cases elevated nuclear PTP activity correlated
      with an increase in the expression of cdc25A. The changes in PTP activity
      observed were not due to any increase in the rate of growth of the colonic mucosa
      as no corresponding changes occurred with PTP activity under conditions of rapid
      mucosal growth.

PMID- 9596995
TI  - A phosphatidylcholine phospholipase C inhibitor, D609, blocks interleukin-3 (IL
      3)-induced bcl-2 expression but not c-myc expression in human IL-3-dependent
      cells.
AB  - Activation of the interleukin-3 (IL-3) receptor is required for the induction of
      cell proliferation and suppression of apoptosis in primitive hematopoietic
      progenitor cells. A rapid activation of tyrosine kinases and a
      phosphatidylcholine-specific phospholipase C has been observed in these cells in
      response to IL-3. The signal transduction cascades regulating cell proliferation
      and the suppression of apoptosis are poorly understood. Using human IL-3
      dependent TF-1 cells, we have found that the tyrosine kinase inhibitor genistein
      blocks both the IL-3 suppression of apoptosis and the expression of the cell
      survival gene bcl-2. In addition, we have found that D609, a specific inhibitor
      of phosphatidylcholine-specific phospholipase C, also inhibits IL-3-induced
      expression of the bcl-2 gene without affecting IL-3-induced tyrosine
      phosphorylation. D609 also drove these cells into apoptosis even in the presence
      of IL-3. Significantly, genistein inhibited the IL-3 induction of both bcl-2 and
      c-myc gene. The latter gene is related to the induction of cell proliferation.
      D609, however, blocked the induction only of the cell survival gene bcl-2. Thus,
      phosphatidylcholine hydrolysis appears linked to the induction of genes related
      to cell survival. These data fit with the hypothesis that there is a bifurcation
      in the signaling pathways downstream of IL-3 receptor-induced tyrosine
      phosphorylation.

PMID- 9596997
TI  - Preparation of phage antibodies to the ED-A domain of human fibronectin.
AB  - The fibronectin (FN) isoform containing the alternative spliced ED-A domain is
      much more expressed in fetal, tumoral, and regenerating tissues than in normal
      adult tissues. The ED-A containing FN is up-regulated by numerous cytokines, such
      as TGF-beta, and, although in normal adult liver the ED-A domain is undetectable,
      in regenerating rat liver the expression of ED-A is increased and mediates the
      conversion of fat storing cells to myofibroblasts. Here we describe the selection
      from a phage display library and the characterization of human antibody fragments
      directed against the ED-A sequence of FN. As they can be easily radiolabeled with
      32P, these antibodies are very highly sensitive reagents for the determination of
      ED-A levels in tissues and biological fluids; in fact, use of these scFv induced
      a more than 10-fold increase in sensitivity with respect to the murine monoclonal
      IST-9. The possibility of preparing a range of human engineered antibodies should
      facilitate the development of antibody reagents with suitable pharmacokinetics,
      valency, functional affinity, and effector functions and that could be useful for
      clinical purposes.

PMID- 9596998
TI  - Immortalization of rat embryo fibroblasts by a 3'-untranslated region.
AB  - We have exploited a cross-species expression screen to search for cellular
      immortalizing activities. A newt blastemal cDNA expression library was
      transfected into rat embryo fibroblasts and immortal cell lines were selected.
      This identified a 1-kb cDNA fragment which has a low representation in the cDNA
      library and is derived from the 3'-UTR of an alpha-glucosidase-related mRNA.
      Expression of this sequence in rat embryo fibroblasts has shown that it is active
      in promoting colony formation and immortalization. It is also able to cooperate
      with an immortalization-defective deletion mutant of SV40 T antigen, indicating
      that it can exert its growth-stimulatory activity in the pathway activated by a
      viral immortalizing oncogene. This is the first example of an immortalizing
      activity mediated by an RNA sequence, and further analysis of its mechanism
      should provide new insights into senescence and immortalization.

PMID- 9596999
TI  - Glucocorticoids induce G1 as well as S-phase lengthening in normal human
      stimulated lymphocytes: differential effects on cell cycle regulatory proteins.
AB  - In order to analyze dexamethasone effects on peripheral blood lymphocyte
      proliferation, we defined various experimental conditions: dexamethasone
      introduced (i) at the time of phytohemagglutinin stimulation, (ii) 48 h after the
      beginning of phytohemagglutinin stimulation, and (iii) on unstimulated
      lymphocytes. In stimulated lymphocytes, we observed an early G1 accumulation (P <
      0.005), a delayed increase in the duration of S-phase (P < 0.03), and a
      consequent increase in cell-cycle duration. The expression of several cyclins,
      cyclin-dependent kinases (CDKs), and CDK inhibitors (CKIs) was modified. Cyclin
      D3, CDK4, and CDK6 involved in G1-phase control were significantly decreased
      under dexamethasone treatment whatever the level of stimulation of lymphocytes
      (stimulated or unstimulated PBL). Cyclin E and CDK2, acting in G1/ S-phase
      transition and S-phase regulation, decreased in stimulated lymphocytes before any
      modification of S-phase (P < 0.002). The expression of CKIs, mainly of p27Kip1,
      appeared to vary with the degree of cell stimulation: a decrease was observed on
      treated unstimulated lymphocytes, while p27Kip1 increased in dexamethasone
      treated cells during stimulation. Our results indicate sequential modifications
      of the cell-cycle regulation by dexamethasone starting with an action on G1
      followed by S-phase control modifications. The protein analysis pinpoints the
      major complexes concerned: CDK4 and CDK6/cyclin D are mainly involved in G1-phase
      modifications, while CDK2 and its partner, cyclin E, might be specifically
      involved in the lengthening of S-phase. The variations observed for p27Kip1 might
      amplify the functional effects of dexamethasone on kinasic complexes.

PMID- 9597000
TI  - Cellular localization and expression of template-activating factor I in different
      cell types.
AB  - Template-activating factors I (TAF-I) alpha and beta have been identified as
      chromatin remodeling factors from human HeLa cells. TAF-I beta corresponds to the
      protein encoded by the set gene, which was found in an acute undifferentiated
      leukemia as a fusion version with the can gene via chromosomal translocation. To
      determine the localization of TAF-I, we raised both polyclonal and monoclonal
      antibodies against TAF-I. The proteins that react to the antibodies are present
      not only in human cells but also in mouse, frog, insect, and yeast cells. The
      mouse TAF-I homologue is ubiquitous in a variety of tissue cells, including
      liver, kidney, spleen, lung, heart, and brain. It is of interest that the amounts
      of TAF-I alpha and beta vary among hemopoietic cells and some specific cell types
      do not contain TAF-I alpha. The level of the TAF-I proteins does not change
      significantly during the cell cycle progression in either HeLa cells synchronized
      with an excess concentration of thymidine or NIH 3T3 cells released from the
      serum-depleted state. TAF-I is predominantly located in nuclei, while TAF-I that
      is devoid of its acidic region, the region which is essential for the TAF-I
      activity, shows both nuclear and cytoplasmic localization. The localization of
      TAF-I in conjunction with the regulation of its activity is discussed.

PMID- 9597001
TI  - Induction of apoptosis in leukemia U937 cells by 5'-deoxy-5'-methylthioadenosine,
      a potent inhibitor of protein carboxylmethyltransferase.
AB  - We found dramatic changes in leukemia U937 cells treated with 5'-deoxy-5'
      methylthioadenosine (MTA), a potent inhibitor of protein
      carboxylmethyltransferase (protein methylase II). Initiation of cell death was
      observed by 1 day after MTA treatment, and it was induced in a dose- and time
      dependent manner. However, cell viability measured by trypan blue exclusion was
      not consistent with the actual percentage of cell death. These results indirectly
      indicated that the type of cell death is apoptosis rather than necrosis. Nuclear
      fragmentation and DNA condensation of MTA-treated U937 cells were analyzed by
      both fluorescent and electron microscopy. MTA-treated cells first began to arrest
      in the M phase of the cell cycle, and they then exhibited a mitotic-like nuclear
      fragmentation process with partially membraneless chromatin. Furthermore, agarose
      gel electrophoresis of DNA extracted from cells treated with MTA showed DNA
      laddering with production of fragments of approximately 200 bp multiples. These
      studies indicated that cell death induced by MTA has the characteristics of
      apoptosis, although nuclear fragmentation is atypical. It seems likely that the
      process of apoptosis in U937 cells induced by MTA correlates with incomplete
      assembly of the nuclear envelope, since MTA itself could inhibit the
      carboxylmethylation of nuclear lamin B and delayed incorporation of lamin B into
      the nuclear envelope.

PMID- 9597002
TI  - G-band expression and megabase fragmentations in apoptosis.
AB  - Apoptosis seems characterized by a cascade of megabase to 200-bp fragmentations
      and by a commitment to perish at the initial level. How that could be achieved
      seems unclear. Preferential cleavage of transcriptionally active chromatin by
      apoptotic nuclease activity has long been suggested. We show here the
      manifestation of self-inflicted G-banding patterns in mitotic chromosomes, or G
      band expression, occurring concurrently with a pattern of megabase fragmentations
      in two apoptotic systems that we have established in human Chang liver cells
      using (a) staurosporine and (b) vanadyl(4) prepulsing. We further show that rare
      cutting NotI and MluI restriction endonucleases with C-G dinucleotide sequence
      specificity had produced similar G-bandings and megabase fragmentations cascading
      down to the 200-bp ladder fragmentation that were also associated with the
      expression of characteristic apoptotic morphologies by the digested cells. CpG
      specific methylation using the methylase SssI abolished the DNA fragmentation
      cascade, G-banding, and apoptotic expressions induced by NotI and MluI,
      implicating endonuclease cleavage of active chromatin, where CpG islands are
      concentrated, as the initiating event. Reproducing the G-bandings and megabase
      fragmentations by directly applying NotI and MluI endonucleases to fixed
      chromosomes and extracted genomic DNA, respectively, further confirmed the notion
      of endonucleolytic cleavage of active chromatin as the causation. Nuclease
      digested light G-band regions of chromosomes appeared to be the chromosome sites
      providing the megabase fragments. Transcriptionally active genes of the genome
      are known to be preferentially cleaved by nuclease activity and are established
      as being concentrated in the light G-bandings that correspond to R-bandings,
      which are also known to be the sites of more frequent cytogenetic breakpoints.
      Manifestation of self-inflicted G-banding patterns (G-banding expression) in
      apoptosis would then imply cleavage of the transcriptionally active genes in
      every light G-band site of every chromosome in the genome. This must be suicidal.

PMID- 9597003
TI  - Senescent WI-38 fibroblasts overexpress LPC-1, a putative transmembrane shock
      protein.
AB  - We have recently reported the isolation of cDNAs for a number of genes that are
      differentially expressed between nonproliferating early (young) and late
      (senescent) population doubling level (PDL) WI-38 human, fetal lung-derived,
      fibroblast-like cells. We now demonstrate that one of these isolates, LPC-1 (Late
      PDL cDNA-1), derives from an approximately 2.9-kb mRNA species that is expressed
      at a two- to fivefold higher level in serum-starved, confluent, senescent versus
      similarly treated young WI-38 cells. Nucleotide sequence analysis of this cDNA
      confirms its identity with that of a cDNA encoding a marker (p63) for the rough
      endoplasmic recticulum and a related swine hepatic cardiogenic shock protein. We
      show that LPC-1 expression in early PDL WI-38 cells is strictly cell cycle
      regulated and its expression peaks 9-12 h after serum stimulation of G0 cultures.
      The steady state levels of LPC-1 transcript in early PDL cells preceeding and
      following its peak expression are low, reflecting basal levels seen in G0 upon
      removal of serum. Late PDL cells, however, seem to have lost this tight cell
      cycle regulation seen in early PDL cells and inappropriately express high levels
      of the transcript after serum stimulation. Specific antiserum detects a protein
      of approximately 63 kDa by Western analysis and elicits intense cytoplasmic
      staining of senescent fibroblasts by immunohistochemistry. Related genomic
      sequences are found in all mammalian species examined as well as in the chicken.
      These findings are consistent with the hypothesis that senescent WI-38 cells
      exhibit a state of growth arrest fundamentally distinct from that of quiescent
      (G0) young cells.

PMID- 9597004
TI  - An active efflux system for heavy metals in cisplatin-resistant human KB
      carcinoma cells.
AB  - The mechanism for cisplatin resistance in cisplatin-resistant KCP-4 cells was
      studied. Although multidrug resistance-associated protein (MRP) was not detected
      in KCP-4 cells, the cells were more resistant to heavy metals than multidrug
      resistant C-A120 cells that overexpressed MRP. KCP-4 cells expressed
      metallothionein, but it was scarcely involved in cisplatin resistance in these
      cells. KCP-4 cells did not express canalicular multispecific organic anion
      transporter (cMOAT). The glutathione (GSH) level was 4.7-fold higher in KCP-4
      cells than in KB-3-1 cells. When the GSH level in KCP-4 cells was decreased by
      treating the cells with buthionine sulfoximine and nitrofurantoin, the
      accumulation of and sensitivity to cisplatin in the cells were increased. C-A120
      cells were only 3.0-fold more resistant to cisplatin than KB-3-1 cells and this
      resistance was not affected by the increased glutathione level. The accumulation
      of platinum in C-A120 and KCP-4 cells was 68.5 and 20.4% of that in KB-3-1 cells,
      respectively, while the intracellular levels of antimony potassium tartrate in C
      A120 and KCP-4 cells were 13.2 and 9.9% of that in KB-3-1 cells, respectively.
      The ATP-dependent efflux of antimony was enhanced in both C-A120 and KCP-4 cells.
      These results, taken together, suggest an efflux pump for heavy metals different
      from MRP and cMOAT is involved in cisplatin resistance in KCP-4 cells.

PMID- 9597005
TI  - Replication of nuclei from cycling and quiescent mammalian cells in 6-DMAP
      treated Xenopus egg extract.
AB  - Nuclear membrane permeabilization is required for replication of quiescent (G0)
      cell nuclei in Xenopus egg extract. We now demonstrate that establishment of
      replication competence in G0 nuclei is dependent upon a positive activity present
      in the soluble egg extract. Our hypothesis is that G0 nuclei lose the license to
      replicate following growth arrest and that this positive activity is required for
      relicensing DNA for replication. To determine if G0 nuclei contain licensed DNA,
      we used the protein kinase inhibitor, 6-dimethylaminopurine (6-DMAP), to prepare
      egg extracts that are devoid of licensing activity. Intact nuclei, isolated from
      mammalian cells synchronized in G1-phase (licensed), G2-phase (unlicensed), and
      G0 were permeabilized and assayed for replication in 6-DMAP-treated and untreated
      extracts supplemented with [alpha-32P]dATP or biotinylated-dUTP. Very little
      radioactivity was incorporated into nascent DNA in each nuclear population;
      however, nearly all nuclei in each population incorporated biotin in 6-DMAP
      extract. The pattern of biotin incorporation within these nuclei was strikingly
      similar to the punctate pattern observed within nuclei incubated in aphidicolin
      treated extract, suggesting that initiation events occur within most replication
      factories in 6-DMAP extract. However, density substitution and alkaline gel
      analyses indicate that the incorporated biotin within these nuclei arises from a
      small number of active origins which escape 6-DMAP inhibition. We conclude that 6
      DMAP-treated egg extract cannot differentiate licensed from unlicensed mammalian
      somatic cell nuclei and, therefore, cannot be used to determine the "licensed
      state" of G0 nuclei using the assays described here.

PMID- 9597006
TI  - Dissociation of telomere dynamics from telomerase activity in human thyroid
      cancer cells.
AB  - Prevention of telomere erosion through acquisition of telomerase activity is
      thought to be an essential mechanism in most human cancer cells for avoidance of
      cellular senescence and crisis. It has been generally assumed that once
      telomerase has been activated, no further telomere shortening should ensue. We
      show here, however, that a much more complex pattern of telomere dynamics can
      exist in telomerase-positive immortal cancer cells. Using a panel of subclones
      derived from a human thyroid cancer cell line, K1E7, we found that some clones
      show persistent decline in mean telomere restriction fragment (TRF) length by up
      to 2 kb over 450 population doublings (pd), despite sustained high telomerase
      activity (as assessed by the in vitro "TRAP" assay). TRF length subsequently
      stabilized at around 5 kb, but with no corresponding increase in telomerase
      activity. One clone showed an even more unexpected biphasic time course, with the
      mean TRF length initially increasing by 1.5 kb over 90 pd, before "plateauing"
      and then returning over a similar period to its original value, again without any
      correlation to TRAP activity. Such dissociations between telomere dynamics and
      telomerase activity support the existence of additional controls on telomere
      length in the intact cell. Our observations are consistent with current negative
      feedback models of telomere length regulation by telomere binding proteins and
      these cell lines should prove useful experimental tools for their further
      evaluation.

PMID- 9597007
TI  - The signals for starvation response are transduced through elevated [Ca2+]i in
      Dictyostelium cells.
AB  - The mechanism by which cells recognize starvation to allow subsequent cellular
      development was analyzed using Dictyostelium discoideum, with special emphasis on
      Ca2+ as a crucial signal transducer in intra- and intercellular communications.
      As was expected, the cytosolic Ca2+ concentration ([Ca2+]i) in aequorin
      expressing cells (RHI76 derived from D. discoideum Ax-3) was temporarily
      increased, when 3-5 microM thapsigargin (Tg), a specific inhibitor of the Ca(2+)
      ATPase, was added into the cells incubated in semistarvation medium (SS-medium: 1
      vol of growth medium plus 7 vol either of 20 mM Na2/K-phosphate buffer (pH 6.2)
      or of Bonner's salt solution (BSS)). Essentially the same result was obtained by
      the application of 5 microM nigericin (Ng), an acid ionophore to cells under the
      semistarved condition. Here it is of interest to note that in the SS-medium Tg
      and Ng are capable of enhancing cell differentiation as exemplified well by the
      earlier acquisition of chemotactic response to cAMP, possibly inducing the
      starvation response through the [Ca2+]i increase. From Western blot analysis of
      phosphotyrosine (pTyr)-containing proteins using anti-pTyr antibody, it was found
      that the pTyr-phosphorylation levels of 97-, 80-, and 45-kDa proteins increase
      specifically in response to starvation. Interestingly, Tg and Ng induced such a
      change of the 80-kDa protein in the cells incubated in the SS-medium. Taken
      together these results strongly suggest that the temporal increase of [Ca2+]i may
      be a matter of importance for signal transduction coupled with starvation
      response.

PMID- 9597008
TI  - The roles of protein kinase C beta I and beta II in vascular smooth muscle cell
      proliferation.
AB  - The role of protein kinase C (PKC) on proliferation of A10 vascular smooth muscle
      cells (VSMC) was studied by overexpressing specific PKC-beta I and -beta II
      isozymes. PKC-beta I and -beta II are derived from alternative splicing of the
      exon encoding the carboxy-terminal (C-terminal) 50 or 52 amino acids,
      respectively. The differential functions of the two isozymes with regard to cell
      proliferation, DNA synthesis, and the cell cycle were investigated in A10 cells,
      a clonal cell line of VSMC from rat aorta, and in A10 cells overexpressing PKC
      beta I and PKC-beta II (beta I-A10 and beta II-A10). PKC levels were increased
      three- to fourfold in heterogeneous cultures of stably transfected cells.
      Although doubling time of A10 cells was 36 h, the cell doubling time in beta I
      A10 cells decreased by 12 h, and, in contrast, the doubling time of beta II-A10
      cells increased by 12 h compared to A10 cells. The increase of [3H]thymidine
      (TdR) incorporation was accelerated and increased in beta I-A10 cells, but slowed
      and diminished in beta II-A10 cells compared to A10 and control cells transfected
      with empty vector. Cell cycle analysis of beta I-A10 cells showed an acceleration
      of S phase entry while beta II-A10 cells slowed S phase entry. These results
      suggest that PKC-beta I and PKC-beta II regulate cell proliferation
      bidirectionally and that PKC-beta I and PKC-beta II may have distinct and
      opposing functions as cell cycle check point mediators during late G1 phase and
      may regulate S phase entry in A10 VSMC.

PMID- 9597009
TI  - Growth-regulatory activity of the growth arrest-specific gene, GAS1, in NIH3T3
      fibroblasts.
AB  - The growth arrest-specific gene, Gas-1, is preferentially expressed in quiescent
      NIH3T3 cells and inhibits DNA synthesis, suggesting that Gas-1 may be a tumor
      suppressor gene. When GAS1 cDNA, under the control of the strong constitutive CMV
      promoter, was transfected into NIH3T3 cells, no stable transfectant cell lines
      were produced, confirming that high levels of expression of GAS1 mRNA inhibit
      proliferation. GAS1, under the control of a dexamethasone-inducible promoter, was
      also transfected into NIH3T3 cells, resulting in normal numbers of transfectant
      clones. When expression of GAS1 mRNA was induced with dexamethasone, the growth
      rate was greatly inhibited. Morphological changes characteristic of growth arrest
      were also observed. To determine if antisense inhibition of expression of Gas-1
      will transform normal fibroblasts, GAS1 cDNA, cloned in the antisense
      orientation, was transfected into NIH3T3 cells and expression of endogenous Gas-1
      mRNA was inhibited. The GAS1-antisense cells had altered morphology and grew to a
      much higher saturation density than control cell lines with a loss of contact
      inhibition. However, there was no change in requirements for serum or any
      development of anchorage-independence. Antisense inhibition of expression of GAS1
      is therefore insufficient to transform the cells, suggesting that additional
      genetic events are required for a fully malignant phenotype.

PMID- 9597010
TI  - Negative cooperativity between alpha 3 beta 1 and alpha 2 beta 1 integrins in
      human mammary carcinoma MDA MB 231 cells.
AB  - The alpha 3 beta 1 integrin has been implicated as a receptor for several matrix
      components, including collagen, fibronectin, and laminins. The function of alpha
      3 beta 1 seems to be very versatile involving cell adhesion to or migration on
      ECM, establishment of cell-cell contacts in aggregates, as well as linkage to
      intracellular tyrosine phosphorylation cascades. Here we report a strong
      induction of attachment of alpha 3 beta 1 integrin expressing human breast
      carcinoma cell line MDA MB 231 to matrix proteins by two alpha 3 integrin subunit
      function-blocking monoclonal antibodies (P1B5 and ASC-1). In contrast,
      stimulation of adhesion to ECM by inhibitory alpha 3 integrin-specific antibodies
      was not observed in the alpha 3 beta 1 integrin-expressing nonmalignant human
      mammary epithelial cell line MCF-10A or the human breast carcinoma cell line MDA
      MB 468 that expressed relatively low amounts of alpha 3 beta 1 integrin at the
      cell surface. This increase was specific for collagens and not observed on
      fibronectin or laminin. Physiological concentrations of bivalent cations were not
      required. MAb P1B5 did not induce homotypic aggregation of MDA MB 231 cells. The
      P1B5-induced increase in cell attachment to collagens could be prevented but not
      reduced below control levels by blocking mAb to the alpha 2 integrin subunit.
      Function blocking anti-alpha 5 integrin subunit mAb was without effect while anti
      beta 1-mAb completely abolished adhesion. Our data indicate that negative
      cooperativity between integrins results in transdominant inhibition of alpha 2
      beta 1 function by alpha 3 beta 1 in human MDA MB 231 but not MDA MB 468 tumor
      cells or nonmalignant MCF-10A cells.

PMID- 9597011
TI  - Decreased PDGF receptor kinase activity in fibroblasts contracting stressed
      collagen matrices.
AB  - Fibroblasts cultured in mechanically stressed collagen matrices proliferate,
      whereas cells in floating collagen matrices become quiescent. Previous research
      indicated that one factor contributing to cell quiescence in floating matrices
      was reduced receptor autophosphorylation in response to PDGF stimulation (i.e.,
      PDGF receptor desensitization). To learn more about the mechanism of PDGF
      receptor desensitization, we analyzed changes in PDGF receptor
      autophosphorylation and receptor kinase activity after stressed collagen matrices
      were switched to floating conditions, which results in rapid cell contraction and
      dissipation of mechanical stress. PDGF receptor desensitization occurred during
      contraction stimulated by serum but not in the absence of serum, and
      desensitization was prevented by inhibitors of contraction but not by inhibitors
      of the contraction-activated cyclic AMP signaling pathway. Receptor
      desensitization resulted from decreased receptor kinase activity rather than from
      elevated protein tyrosine phosphatase activity, and only receptors unoccupied at
      the time of contraction were affected. After contraction, radiolabeled PDGF
      binding to the cells was decreased, which suggested that receptor desensitization
      resulted from a contraction-dependent change in receptor availability or
      affinity.

PMID- 9597012
TI  - Hepatic sinusoidal endothelium heterogeneity with respect to the recognition of
      apoptotic cells.
AB  - The recognition and removal of human apoptotic peripheral lymphocytes in selected
      populations of periportal and perivenous endothelial cells was studied in in situ
      and in vitro experiments. Apoptotic peripheral blood lymphocytes once injected
      into the liver circulation were retained by the sinusoids showing a large
      heterogeneity of distribution: apoptotic cells are found in the periportal tract
      double the amount found in the perivenous region. Apoptotic PBL adhesion was
      lowered to a sixth of the control after preinjection with a sugar mixture
      (Mannose, N-acetylgalactosamine, N-acetylglucosamine, D-galactose), as suggested
      by the expression of modified surface glycoconjugates on the plasma membrane of
      apoptotic cells. A bimodal profile of the distribution of the hepatic sinusoidal
      cell population, regarding the number of galactose and mannose receptors and the
      porosity index, was found. Two endothelial cell subsets were present: low
      porosity cells (average index 14 +/- 6%; periportal tract) with a high number of
      carbohydrate binding sites, and high porosity cells (average index 26 +/- 7%;
      perivenous tract), with a low number of carbohydrate binding sites.

PMID- 9597013
TI  - Medicare expansions 35 years later.

PMID- 9597014
TI  - Health plan report cards and insurance choice.
AB  - This paper examines the relationship between consumers' health plan choices and
      health plan performance ratings. We make use of an initiative at a large firm to
      collect, aggregate, and disseminate to employees plan performance ratings. We
      estimate several statistical models, including share equations--which allow for
      the presence of important unobserved plan attributes--and logit models. Although
      report card ratings appear to be related to enrollment choices, the relationship
      is not uniform. For some dimensions of performance, the results are consistent
      with the hypothesis that employees respond to the performance ratings. For other
      dimensions, the ratings seem less influential than other plan attributes that
      employees likely observed without the data release.

PMID- 9597015
TI  - The association of insurance type with costs of dispensed drugs.
AB  - This study examines the association between types of prescription drug insurance
      coverage and the unit cost of dispensed drugs. Logistic regression and ordinary
      least squares regression were used to assess differences in the use of brand name
      and generic drugs and the unit cost of dispensed brand name or generic drugs
      across four insurance categories: Medicaid, private third party, indemnity, and
      uninsured. The results show that private third-party and indemnity prescriptions
      were more likely to be dispensed with brand name drugs. Also, indemnity patients
      and the uninsured were dispensed brand name and generic drugs with lower unit
      costs. The findings have ramifications for the design of prescription drug
      insurance benefits and suggest that physicians may respond to the economic
      situation of their patients when prescribing drugs.

PMID- 9597017
TI  - Determinants and costs of Medicare post-acute care provided by SNFs and HHAs.
AB  - Provisions in the 1997 Balanced Budget Act affecting Medicare skilled nursing
      facility (SNF) and home health agency (HHA) services heighten the importance of
      knowing more about beneficiary, market, and policy factors that impact use of
      post-acute care and the costs of such services. This study used data from the
      Medicare Current Beneficiary Survey and other sources to address these issues.
      Findings shed light on responses that need to be monitored in light of the
      recently mandated policies and other SNF and HHA options that are being
      considered.

PMID- 9597016
TI  - Transitions in insurance and employment among people with HIV infection.
AB  - This article examines the extent to which people with HIV infection change their
      insurance and employment status over time and investigates the correlates of such
      changes. Data come from the AIDS Cost and Services Utilization Survey, which
      followed 1,949 HIV-infected adults over an 18-month period that began March 1,
      1991. In the first interview, overall, 33% of respondents had private insurance;
      40% had public coverage (i.e., Medicaid, Medicare, CHAMPUS); and 27% had no
      insurance. Among the subgroup with AIDS, corresponding figures were 32%, 54%, and
      14%. Overall, 65% were unemployed; among those with AIDS, 82% were unemployed.
      Over the 18-month period, 23% of respondents reported a change in insurance
      status and 27% reported a change in employment status. Among those who began the
      study with private insurance, only 15% reported losing this coverage. Transitions
      from no insurance to public coverage occurred most frequently. Compared to those
      who began the study with AIDS, those who progressed to AIDS during the study
      period were more likely to experience a change in insurance (18% vs. 32%).
      Consistent with prior studies, public insurance plays a major role in financing
      care for people with HIV infection. Transitions from public coverage to no
      insurance may disrupt access to care.

PMID- 9597018
TI  - Reform of the Medicare AAPCC: learning from previous proposals. Average Adjusted
      Per Capita Costs.
AB  - Since 1982, Medicare has contracted with health maintenance organizations (HMOs)
      on a risk-contract basis, paying plans based on Average Adjusted Per Capita Costs
      (AAPCCs). The calculation of the AAPCCs has been criticized on several fronts. A
      congressional proposal encompassed in the failed 1995 Balanced Budget Act would
      have altered the formula by which Medicare determines payments to risk
      contracting HMOs. Many of its provisions were enacted through the 1997 Balanced
      Budget Act. This paper models the effect of the earlier proposal on AAPCC rates
      and discusses the extent to which the proposal and the reforms in the 1995
      Balanced Budget Act would address shortcomings identified in the original rate
      formula.

PMID- 9597019
TI  - Differences in prescription drug utilization and expenditures between Blacks and
      Whites in the Georgia Medicaid population.
AB  - To address policy concerns regarding prescription drug access by vulnerable
      minority groups, we analyzed prescription drug use and spending among black and
      white enrollees in the Georgia Medicaid program. Using a two-part model
      estimating use and level of use of any prescription drugs, the study examined
      black/white differences controlling for age, sex, and Medicaid eligibility
      characteristics. Results showed black enrollees were significantly less likely to
      use any prescription drugs and received significantly fewer prescriptions than
      white enrollees. After adjustment, the black/white difference for children was
      43%, with black children using 2.7 fewer prescriptions relative to white
      children. Patterns of use were similar for adults and the elderly, with black
      adults using 4.9 fewer prescriptions, and black elders using 6.3 fewer
      prescriptions, than their white peers. Spending rates per full-year enrollee were
      similar to utilization patterns and maintained the black/white differential.
      White Medicaid enrollees had higher use and spending than black enrollees across
      most high-volume therapeutic drug categories. The study explores several possible
      explanations for these differences.

PMID- 9597021
TI  - Behind the scenes at the Journal: how manuscripts get into print.

PMID- 9597020
TI  - New diabetes insurance laws present challenges for states.

PMID- 9597022
TI  - How can public awareness of dietetics be increased? A member offers a solution.

PMID- 9597023
TI  - Future need for more cancer research.

PMID- 9597024
TI  - Oxidative DNA damage levels in blood from women at high risk for breast cancer
      are associated with dietary intakes of meats, vegetables, and fruits.
AB  - OBJECTIVE: We examined the relationship between intakes of specific foods-
      namely, meats, vegetables, and fruits--with levels of oxidative DNA damage in
      women consuming their own usual diet or a diet low in fat. DESIGN: Blood was
      obtained from women who had been assigned randomly to a low-fat or
      nonintervention diet for 3 to 24 months. Levels of 5-hydroxymethyluracil, a type
      of oxidative DNA damage, were determined. Diet data were obtained from 3-day food
      records. SUBJECTS/SETTING: The 21 women were participating in an outpatient
      clinic. All the women were healthy but had a first-degree relative with breast
      cancer. INTERVENTION: The intervention was a self-selected diet with a goal of
      15% of energy from fat. MAIN OUTCOME MEASURES: Existing data on oxidative DNA
      damage levels were evaluated for possible relationships to foods eaten. Intakes
      of raw and cooked vegetables were examined separately. Meat intake was examined
      by type of meat (pork, beef, fish, chicken) and by cooking temperature.
      STATISTICAL ANALYSES: Initial univariate analyses relied on Spearman rank
      correlations of each food item with DNA damage. Further analyses of the data were
      performed with univariate and multivariate weighted least squares regression
      models. RESULTS: The model that best explained DNA damage levels was a bivariate
      regression model that included the intake of cooked vegetables and the sum of
      beef and pork intake. This model accounted for 85% of the variation in DNA damage
      levels among women. Preliminary results are suggestive of a positive association
      of DNA damage with beef and pork intake and a negative association with cooked
      vegetable intake. APPLICATION: These observations, if confirmed in larger
      studies, suggest specific dietary changes to reduce oxidative DNA damage levels
      and possibly cancer risk.

PMID- 9597026
TI  - Dietary sources of nutrients among US adults, 1989 to 1991.
AB  - OBJECTIVE: To identify major food sources of 27 nutrients and dietary
      constituents for US adults. DESIGN: Single 24-hour dietary recalls were used to
      assess intakes. From 3,970 individual foods reported, 112 groups were created on
      the basis of similarities in nutrient content or use. Food mixtures were
      disaggregated using the US Department of Agriculture (USDA) food grouping system.
      SUBJECTS/SETTING: A nationally representative sample of adults aged 19 years or
      older (n = 10,638) from USDA's 1989-91 Continuing Survey of Food Intakes by
      Individuals. ANALYSES PERFORMED: For each of 27 dietary components, the
      contribution of each food group to intake was obtained by summing the amount
      provided by the food group for all respondents and dividing by total intake from
      all food groups for all respondents. RESULTS: This article updates previous work
      and is, to the authors' knowledge the first to provide such data for carotenes,
      vitamin B-12, magnesium, and copper. Beef, yeast bread, poultry, cheese, and milk
      were among the top 10 sources of energy, fat, and protein. The following other
      major sources also contributed more than 2% to energy intakes: carbohydrate:
      yeast bread, soft drinks/soda, cakes/cookies/ quick breads/doughnuts,
      sugars/syrups/jams, potatoes (white), ready-to-eat cereal, and pasta; protein:
      pasta; and fat: margarine, salad dressings/mayonnaise, and cakes/ cookies/quick
      breads/doughnuts. Ready-to-eat cereals, primarily because of fortification, were
      among the top 10 food sources for 18 of 27 nutrients. APPLICATIONS/CONCLUSIONS:
      These analyses are the most current regarding food sources of nutrients and,
      because of disaggregation of mixtures, provide a truer picture of contributions
      of each food group.

PMID- 9597025
TI  - Stages of change for reducing dietary fat intake over 18 months.
AB  - OBJECTIVE: To describe the stages of change that take place over 18 months, using
      the criterion of fat intake < or = 30% of total energy to define effective action
      and to investigate the effect of a single dietary feedback report on dietary fat
      reduction. DESIGN: Subjects were randomly assigned to experimental or control
      conditions and assessed at 0, 6, 12, and 18 months for fat intake and stage of
      change. Subjects in the experiment group received 1 feedback report at baseline;
      all subjects received a report at 12 months. SUBJECTS: Potential subjects (n =
      614) were recruited by mail from a random sample of nonsmoking adults (32%
      response rate). Subjects were excluded if consuming < or = 30% of energy from fat
      or if pregnant or lactating (n = 145). Although 83% of subjects (n = 389)
      completed the 18-month study, only 296 provided complete data for all time
      points. The study was restricted to these 296. INTERVENTION: Dietary feedback
      reports plus brief educational materials were provided following the experiment
      design. ANALYSES: Repeated measures analysis of variance with fat intake (percent
      of energy from fat) as the dependent variable and baseline stage and condition as
      independent variables. In addition, t tests were used to compare groups at
      specific time points. RESULTS: There was a main effect for time (F3,286 = 39, P <
      .0001) and baseline stage (F3,286 = 24, P < .0001), but no effect of feedback.
      There was a time-by-feedback interaction (F4,286 = 4.7, P < .01). There was a
      short-term effect of feedback over 6 months (t = 3.8, P < .001), but this effect
      was not significant at other time points. About 9% to 12% of subjects in the
      precontemplation or contemplation stages, 24% of subjects in the preparation
      stage, and 40% of unclassified subjects at baseline progressed to the action
      stage by 18 months. Between 12 and 18 months, subjects progressing at least 1
      stage reduced their fat intake to a greater extent than subjects who failed to
      progress (t = 5.1, P < .0001). IMPLICATIONS: Interventions targeted to stage of
      change have the potential for accelerating the rate of change for dietary fat
      reduction, but reaching the goal of fat intake < or = 30% of total energy may
      require more intensive interventions than a single dietary feedback report.

PMID- 9597027
TI  - Risk indicators for malnutrition are associated inversely with quality of life
      for participants in meal programs for older adults.
AB  - OBJECTIVE: To evaluate the nature and strength of associations between quality of
      life and factors commonly linked with malnutrition in participants in a meal
      program for the elderly. DESIGN: A questionnaire that assessed quality of life,
      nutritional risk, quality of health, depression, social satisfaction, functional
      status, food security, and food enjoyment was administered. SUBJECTS/SETTING: All
      persons aged 60 years and older enrolled in the Title III-C meal program in Pepin
      County, Wisconsin, during a 1-month period were asked to participate. Of 180
      eligible subjects, data were available for 155; 108 received meals at congregate
      sites and 47 received home-delivered meals. STATISTICAL ANALYSES PERFORMED:
      Descriptive statistics were used to characterize the population. Independent
      samples t tests and chi 2 analysis were used to test for differences between the
      congregate-meal group and home-delivered-meal group. Spearman correlation
      coefficients were used to determine the direction and magnitude of associations
      between scale variables and quality of life. RESULTS: Quality of life and quality
      of health were positively correlated (r = .83, P < .0001). Nutritional risk, food
      insecurity, decreased enjoyment of food, depression, and impaired functional
      status were all negatively associated with quality of life. This research offers
      evidence that there are measurable associations between nutritional factors and
      quality of life. APPLICATIONS: Our finding could be helpful to dietitians in
      justifying, planning, and evaluating nutrition programs and interventions.
      Quality of life in older adults may be further enhanced by programs that include
      social and psychological components in addition to elements oriented to reduce
      nutritional risk.

PMID- 9597028
TI  - Nutrition and health status assessment of community-residing elderly in New York
      City: a pilot study.
AB  - Ninety-five percent of persons over the age of 65 years live in the community and
      benefit from community-based health and nutrition services. The purpose of this
      project was to evaluate diet, function, and mental health in 40 men and women
      aged 65 years and older who were residing in a large metropolitan community.
      Nutritional status was assessed using two 24-hour recalls, 5 days of food
      records, a food frequency, and anthropometric measurements. Participants
      responded to standardized activities of daily living and instrumental activities
      of daily living instruments and an investigator-developed, performance-based
      appraisal of food preparation and management. Cognition and mood were assessed
      using the Folstein Mini-Mental Examination and the Yesavage Depression Scale. The
      nutrient intakes for individuals were compared with the Recommended Dietary
      Allowances (RDAs) and the Food Guide Pyramid. Mean energy intake was 1,625 kcal
      (range = 787 to 2,910 kcal); 7 persons consumed more than 2,000 kcal. The mean
      vitamin and mineral intake for participants met the RDAs except for calcium,
      vitamin D, zinc, and magnesium intakes. The average percentages of carbohydrate,
      protein, and fat were 53%, 16%, and 30%, respectively. Nutritional assessments of
      subjects with and without congregate meals were contrasted. Six of the 13
      congregate-meal participants were at nutritional risk, compared with 6 of 27 not
      receiving congregate meals. The interrelationships of diet, functional status,
      and mental health factors were examined along with recommendations for future
      data collection in similar studies.

PMID- 9597029
TI  - Factors influencing nutrition education for patients with low literacy skills.
AB  - Although there has been increasing attention to cancer prevention among low
      income and minority populations, only a few nutrition interventions have
      addressed the special needs of people with low literacy skills. To determine the
      best provider and the most effective format for a nutrition intervention
      targeting patients with low literacy skills, we conducted interviews with
      literacy experts and health care providers and focus groups with members of adult
      basic education classes. Thirty-five literacy experts and health-center-based
      physicians, nurses, and nutritionists in Boston, Mass, were interviewed. In
      addition, 50 volunteer clients from 4 Boston-based adult basic education programs
      participated in 6 focus groups. Results suggested that health care providers
      consider nutrition to be a fundamental health education topic, but that its
      successful inculcation in patients with limited literacy skills is hindered
      mostly by insufficient provider time. Almost all providers agreed that patients
      need to be referred to nutritionists for nutrition education. Although most
      providers and patients acknowledged that patients perceive physicians to be the
      authorities on health, patients with low literacy skills turned first to family
      members and friends for health information. These results suggest that effective
      nutrition interventions must build on patients' social networks; appear in a
      visually based, interactive format; and be culturally appropriate.

PMID- 9597030
TI  - Olestra: a new food additive.
AB  - In 1987, Procter and Gamble Company (Cincinnati, Ohio) petitioned the US Food and
      Drug Administration (FDA) to amend the food additive regulations to allow sucrose
      esterified with fatty acids (olestra) to be used as a replacement for
      conventional fats. The petitioner later restricted its request for use in savory
      snacks. FDA considered evidence submitted by the petitioner, the opinions of
      experts, proceedings from the FDA Food Advisory Committee, and public discussion
      and concluded on January 25, 1996, that olestra was safe for use in savory snacks
      (eg, salty snacks such as potato chips, corn chips). Olestra is not toxic,
      carcinogenic, genotoxic, or teratogenic and is neither absorbed nor metabolized
      by the body, but may be associated with gastrointestinal tract symptoms such as
      cramping or loose stools. In addition, olestra affects the absorption of fat
      soluble vitamins but does not affect the absorption of water-soluble nutrients.
      The petitioner's studies concluded that when olestra was consumed with foods
      containing vitamins A, D, E, or K, the fat substitute could have an effect on the
      absorption of these nutrients. Therefore, FDA is requiring that fat-soluble
      vitamins lost through absorption be added back to olestra as follows: 170 IU
      vitamin A per gram olestra, 12 IU vitamin D per gram olestra, 2.8 IU vitamin E
      per gram olestra, and 8 micrograms vitamin K per gram olestra. As part of the
      conditions of approval FDA is requiring that the food labels of products
      containing olestra disclose the vitamin compensation and the potential
      gastrointestinal effects. FDA is also requiring that further studies examining
      consumption patterns and the effects of olestra on human beings be conducted.

PMID- 9597031
TI  - Validating fourth-grade students' self-report of dietary intake: results from the
      5 A Day Power Plus program.

PMID- 9597032
TI  - Family functioning is related to overweight in children.

PMID- 9597033
TI  - Self-reported energy intake and energy expenditure in elderly women.

PMID- 9597034
TI  - Fruit and juice intake associated with higher Dietary Status Index in rural east
      Tennessee women living in public housing.

PMID- 9597035
TI  - Position of the American Dietetic Association: use of nutritive and nonnutritive
      sweeteners.

PMID- 9597036
TI  - President's page: checking the strategic framework road map.

PMID- 9597037
TI  - JCAHO and CDR: meeting the competence challenge. Joint Commission on the
      Accreditation of Healthcare Organizations. Commission on Dietetic Registration.

PMID- 9597038
TI  - Effects of aging and food restriction on the antioxidant enzyme activity of rat
      livers.
AB  - The effects of aging and food restriction on the activities and mRNA levels of
      antioxidant enzymes in rat livers were examined. Rats were fed ad libitum every
      day (AL) or ad libitum on every other weekday (FR). At 30 months of age, the
      catalase and glutathione peroxidase activities were lower, whereas the
      thiobarbituric acid (TBA) value, an index of lipid peroxidation of the AL rats,
      was higher than that at younger ages. At 33 months of age, copper/zinc superoxide
      dismutase (CuZnSOD), catalase, and glutathione peroxidase activities increased,
      and the TBA value of the FR rats remained unchanged as compared with those at
      younger ages. Until old age, food restriction gave rather decreasing effects on
      antioxidant enzyme activities. Furthermore, antioxidant enzyme activities and the
      TBA values of the FR rats were higher at the end of a fasting period than those
      at the end of a feeding period.

PMID- 9597039
TI  - Diet restriction increases apoptosis in the gut of aging rats.
AB  - Previous studies have shown that epithelial cell production rates are increased
      throughout the gastrointestinal tract in aging rats. We tested the hypothesis
      that alteration in cell death (apoptosis) might be involved. Fischer 344 rats
      aged 4-5 months and 24-25 months fed ad libitum (AL) or calorie restricted (CR)
      to 60% of the AL intake were studied. Epithelial cell apoptosis was determined by
      a terminal deoxyuridine nucleotidyl nick end labeling (TUNEL) technique validated
      in our laboratory, and the expression of four members of the Bcl-2 family was
      evaluated by Western blotting in the small intestine and colon. The apoptotic
      index was low in young and aging AL and young CR rats. However, CR in aging rats
      was associated with a significantly higher apoptotic index in the jejunum and
      colon. The expression of the Bcl-2 family of genes was unchanged. Enhanced
      apoptosis in CR may protect the gastrointestinal tract from accumulation of DNA
      altered cells during the aging process.

PMID- 9597040
TI  - Dietary self-selection can compensate an age-related decrease of rat liver 20 S
      proteasome activity observed with standard diet.
AB  - Aged Lou female rats (33 months) submitted to a self-selection regimen showed a
      decrease in protein intake (down to 11% of the total intake), whereas mature rats
      (18 months) selected a high percentage of protein (20% of the total intake)
      similar to the protein content of the standard diet. To find out if this decrease
      in protein intake would prevent an observed age-related decrease in proteasome
      activity, four peptidase activities and oxidized protein degradation were tested
      with proteasome purified from the liver of 18- and 33-month-old rats. The
      peptidylglutamyl-peptide hydrolase activity, which is decreased with age for rats
      fed the standard diet, was restored in the self-selecting old rats to the level
      observed for the mature rats. Degradation of oxidized glutamine synthetase, which
      is also decreased with age for rats fed the standard diet, was partly restored.
      Proteasome from self-selecting old rats showed a slight increase in trypsin-like
      and chymotrypsin-like activities as compared to proteasome from old rats fed the
      standard diet. Two-dimensional gel electrophoresis followed by quantitative
      analysis of the pattern of proteasome subunits revealed an increase in the
      intensity of two protein spots for proteasome from old rats fed the standard diet
      as compared with proteasome from either mature rats or self-selecting old rats.
      These findings may have important implications in aging for proteasome-mediated
      proteolysis and subsequent accumulation of oxidatively damaged protein.

PMID- 9597041
TI  - Caloric intake alters the efficiency of catalase mRNA translation in the liver of
      old female mice.
AB  - The free radical theory of aging predicts that calorie restriction, which extends
      life span, should reduce oxidant damage. In mammals, the oxidative processes
      centered in the liver are a major source of free radicals. Liver catalase has the
      dominant role in the intracellular detoxification of hydrogen peroxide. In male
      rodents, published studies indicate that aging decreases catalase gene
      transcription and that calorie restriction obviates this effect. In females,
      published studies are inconsistent, and no molecular mechanisms have been
      identified. Here we report that, in female mice, aging can lead to an increase in
      the translational efficiency of hepatic catalase mRNA, and that calorie
      restriction obviates this effect. Consideration of these results and published
      studies leads us to propose that the variability in catalase results in females
      may arise from the small number of studies or from unique aspects of female
      physiology, perhaps the estrous cycle and its cessation with age.

PMID- 9597042
TI  - The production of the Alzheimer amyloid precursor protein (APP) in extraneuronal
      tissue does not increase in old age.
AB  - Alzheimer's disease (AD) is characterized by the cerebral deposition of beta
      amyloid (A beta). A beta plaques also occur in the brains of healthy aged
      individuals, and A beta concentrations are increased in the cerebrospinal fluid
      (CSF) in old age. Based on results from an in vitro senescence model on human
      fibroblasts, it was proposed that the production of the beta-amyloid precursor
      protein (APP) was increased during aging. No information was available as to
      whether APP production was also augmented in aged humans. It was therefore the
      aim of the present study to analyze APP in connective tissue, skeletal muscle,
      peripheral blood mononuclear cells, and serum samples from young and aged healthy
      individuals. APP production was assessed by Northern and Western blotting. The
      expression of the different APP isoforms was studied by reverse transcription
      polymerase chain reaction (RT-PCR) technique. The results demonstrate that APP
      messenger ribonucleic acid (mRNA) and protein concentrations were identical in
      blood and tissue samples from young and aged individuals and that there were no
      age-dependent changes in the APP isoform production pattern. Thus, our data
      strongly argue against the possibility of an altered production of APP during
      healthy aging and underline the point that in vitro aging models may not
      accurately reflect the in vivo situation.

PMID- 9597043
TI  - Alterations in the opioid control of LHRH release from hypothalami isolated from
      aged male rats.
AB  - Several lines of evidence have suggested that the opioid control of gonadotropin
      secretion in the male rat is altered with aging. Because neural control of
      gonadotropins is mediated through luteinizing hormone releasing hormone (LHRH)
      secreting neurons, we examined the postulated changes in the opioid control of
      gonadotropins more directly by studying isolated hypothalamic fragments in vitro.
      Hypothalami from young (75-90 days) and old (18-20 months) males were examined
      for their ability to release LHRH when incubated with increasing doses of
      naloxone in a semi-static culture system. Serum concentrations of testosterone
      and luteinizing hormone (LH) in the donor animals were both significantly lower
      in old male rats compared with young males. Basal secretion of LHRH was similar
      in both age groups. Two-way repeated measures ANOVA indicated that naloxone
      stimulated a significant dose-dependent increase in the release of LHRH into the
      media. ANOVA also indicated a significant effect of age. We conclude that the
      changes in the endogenous opioid systems reported to occur with aging are, in
      fact, linked to differences in LHRH secretion and thus to differences in the
      dynamic relationship between testosterone and LH in older male rats.

PMID- 9597044
TI  - Prevalence of CD8+ T-cell expansions in relation to age in healthy individuals.
AB  - Clonal CD8+ T-cell expansions have been identified in the peripheral blood of
      healthy adults and occasionally in children. These expansions are often large,
      yet their etiology is unknown. This study evaluated the relationship between age
      and the prevalence of these expansions in a healthy population (n = 147) aged 9
      months to 85 years. Expansions were determined using immunofluorescence staining
      with monoclonal antibodies to different T-cell receptor (TCR)-variable regions.
      The overall prevalence was 13.6% and increased linearly with age as follows: 0%
      for 9-month-olds, 2.7% for 4- to 12-year-olds, 13.3% for 20- to 30-year-olds,
      20.7% for 35- to 50-year-olds, and 33.4% for 65- to 85-year-olds. Multiple
      expansions were observed only in the oldest group. Certain TCR-variable regions
      appeared to be preferentially utilized by these expansions, which suggests a
      response to a particular antigenic stimulus. Childhood illness and vaccination
      histories did not provide insight into the etiology of these expansions. Age was
      the only measured factor that was associated with these expansions.

PMID- 9597045
TI  - Techniques to evaluate elderly human muscle function: a physiological basis.
AB  - Elderly persons appear to exhibit muscle weakness and a slowing in their speed of
      muscle movement. Objective quantification of these characteristics requires
      reliable and practical tests to assess the muscle contractile characteristics of
      elderly people. This review discusses the advantages and limitations of voluntary
      and electrically stimulated muscle testing techniques used to assess the
      strength, speed, and fatigability of elderly muscle with a brief explanation of
      the physiological basis. This review presents the practice and theory underlying
      the scientific measurement of elderly human muscle function, bridging the gap
      between the practical issues of measurement and the physiological significance of
      such measurements.

PMID- 9597046
TI  - Mortality and biomarkers of aging in heterogeneous stock (HS) mice.
AB  - A longitudinal study was undertaken to evaluate the relationships among a battery
      of aging biomarkers and subsequent survival time in 319 genetically heterogenous
      stock (HS) mice. The biomarker variables chosen were selected from the broad
      domains of behavior, homeostatic physiology, oxidative defense, and immune
      function; biomarkers were measured at 45, 90, 360, 630, and 900 days of age. Sex
      differences were found in the survivor and mortality functions, with a mortality
      rate crossover occurring at about 525 days and a survival curve crossover at
      about 750 days of age. Females experienced lower initial mortality but had more
      sharply increasing mortality with age than did males. Survival analysis using
      Gompertz parametric models with biomarkers as time-varying covariates yielded
      significant biomarkers from each domain. Following backward elimination
      procedures, the final set of independent mortality predictors included headpokes
      in the File activity apparatus, maximum cord drop time, weight, hematocrit, urine
      concentration, natural killer cell activity, and concanavalin A response.

PMID- 9597047
TI  - Impaired glutathione peroxidase activity accounts for the age-related
      accumulation of hydrogen peroxide in activated human neutrophils.
AB  - BACKGROUND: As assessed by flow cytometry, the increase in hydrogen peroxide in
      individual neutrophils from old volunteers was significantly greater than in
      neutrophils from young volunteers. To explain the discrepancy in previous reports
      that showed reduced superoxide generation with age and our finding, we measured
      the kinetics of antioxidative enzymes. METHODS: Neutrophils were obtained from
      young (ages 21-34) and old (ages over 65) volunteers. The increase in hydrogen
      peroxide following stimulation with formyl peptide in individual neutrophils was
      assessed by flow cytometry by using dihydrorhodamine 123. The enzyme kinetics was
      determined from the best fit curve using Michaelis-Menten equations. RESULTS:
      Aging was associated with a significant reduction in the Vmax for glutathione
      peroxidase. The decreased activity was not due to selenium deficiency as the
      serum and neutrophil concentrations were identical with age. Following
      activation, a significant increase in the Km was noted in neutrophils from young
      but not from old volunteers. CONCLUSIONS: These results account for the increased
      intracellular accumulation of hydrogen peroxide as a function of age in
      stimulated neutrophils. These results provide evidence in humans of an age
      related impairment in antioxidative defense mechanisms that support the free
      radical theory of aging.

PMID- 9597048
TI  - Serum levels of insulin-like growth factor-I are related to age and not to body
      composition in healthy women and men.
AB  - BACKGROUND: Aging is accompanied by decreased bone and lean body mass, increased
      fat mass, and reduced growth hormone (GH) axis function, reflected in diminished
      levels of insulin-like growth factor-I (IGF-I). Similar changes in body
      composition occur in nonelderly, GH-deficient adults and are reversible with GH
      administration, suggesting that diminished GH/IGF-I axis activity may contribute
      to such age-related changes. To determine the precise pattern of IGF-I decline
      with age, and to test the hypothesis that this decline is related to concomitant
      changes in body composition and bone metabolism independent of age, we conducted
      a cross-sectional survey in 351 healthy participants in the Baltimore
      Longitudinal Study of Aging. METHODS: We evaluated relationships among IGF-I,
      age, and total and regional adiposity, as assessed by body mass index (BMI) and
      waist-to-hip ratio (WHR); lean body mass, as estimated from urinary creatinine
      excretion (Crex/ht); bone mineral density (BMD), as assessed by single and dual
      photon absorptiometry scanning; and circulating levels of parathyroid hormone
      (PTH), 1,25-(OH)2 D3, 25-OHD, and osteocalcin. RESULTS: Serum IGF-I levels
      declined with age (p < .0001) in both men (r = -.51) and women (r = -.67). In
      men, the decline was linear, whereas IGF-I levels decreased faster in women < 45
      years of age than in older women (p < .01) or in men (p < .001). IGF-I was
      inversely related to BMI (p < .005), WHR (p < .001), and PTH (p < .01) in women.
      IGF-I was positively related to BMD of the hip and radius in both genders (p <
      .0003) and to Crex/ht (p < .0005) and osteocalcin (p < .0001) in men. With
      increasing age, Crex/ht and BMD decreased (p < .0001) and WHR, PTH, and
      osteocalcin increased (p < .005) in both genders, whereas BMI increased only in
      women (p < .005). After adjustment for age, IGF-I was not significantly related
      to BMI, WHR, Crex/ht, or BMD in either gender. IGF-I was positively related to
      1,25-(OH)2 D3 (p < .01) independently of age in women. CONCLUSIONS: Advancing
      age, rather than declining serum levels of IGF-I, appears to be a major
      determinant of life-time changes in body composition and BMD in women and men.

PMID- 9597049
TI  - Side effects resulting from the use of growth hormone and insulin-like growth
      factor-I as combined therapy to frail elderly patients.
AB  - BACKGROUND: The objective of this study was to examine the relationship between
      serum IGF-I concentration and the incidence of side effects of therapy with
      recombinant human growth hormone (rhGH) and recombinant human insulin-like growth
      factor-I (rhIGF-I). METHODS: Thirteen high-risk, undernourished elderly males
      were started on a 15-day course of rhGH and rhIGF-I by subcutaneous injection.
      The dose of rhGH was held constant at .0125 mg/kg/day, whereas the dose of rhIGF
      I was increased in a stepwise fashion from 10 micrograms/kg to the targeted dose
      of 40 micrograms/kg twice a day. RESULTS: Nine subjects completed the protocol
      and reached the full target dose of both hormones. Fluid retention, gynecomastia,
      and orthostatic hypotension were the most common complications. The hormone
      injections increased the serum concentration of IGF-I (from 72.7 +/- 40.9 to
      483.7 +/- 251.4 eta g/ml, p = .001) and IGFBP-3 (from 1.82 +/- 0.66 to 2.72 +/-
      1.18 mg/L, p = .012), and decreased serum albumin (from 34.3 +/- 5.5 to 31.4 +/-
      4.6 g/L, p = .009). The magnitude of the initial increase in the serum IGF-I
      concentration was a powerful risk factor for severe orthostatic hypotension,
      diffuse myalgias, and drug-induced hepatitis. There was no association between
      the serum IGF-I concentration and fluid retention or gynecomastia. CONCLUSIONS:
      Treatment of the undernourished frail elderly with the anabolic agents rhGH and
      rhIGF-I at the specified dosages may produce undesirable side effects including
      fluid retention, gynecomastia, and orthostatic hypotension. Although these agents
      hold therapeutic promise, they must be used with caution in this high-risk
      population.

PMID- 9597050
TI  - The association between chronic diseases and depressive symptomatology in older
      Mexican Americans.
AB  - BACKGROUND: Among the elderly population, the risk for psychological distress
      increases with the number of chronic diseases and accompanying functional
      disability. The prevalence of chronic medical conditions and functional
      disability varies substantially across ethnocultural groups, however. Using data
      from the Hispanic EPESE, we previously reported that among older Mexican
      Americans, the total number of chronic medical conditions and the presence of
      functional impairment are strong predictors of depressive symptoms. METHODS:
      Using multiple regression, we examined the association between specific chronic
      diseases, individual functional disabilities, and depressive symptoms in this
      group of ethnic elders. RESULTS: Multiple regression models indicated that
      diabetes (OR = 1.25, 95% CI = 1.03-1.56), arthritis (OR = 1.42, 95% CI = 1.17
      1.72), urinary incontinence (OR = 1.94, 95% CI = 1.46-2.59), bowel incontinence
      (OR = 2.28, 95% CI = 1.15-4.55), kidney disease (OR = 3.11, 95% CI = 1.13-8.58),
      and ulcers (OR = 2.56, 95% CI = 1.23-5.29) were predictive of high levels of
      depressive symptoms. Hip fracture, although recognized as having a substantial
      impact on functional status, was not found to be associated with depressive
      symptoms. History of stroke was not significantly associated with depressive
      symptoms in bivariate or multivariate analyses, but history of stroke with
      residual speech problems was predictive (OR = 2.16, 95% CI = 1.01-4.79). Among
      specific activities of daily living, only impaired ability to walk across a room
      (OR = 1.65, 95% CI = 1.04-2.73) or to bathe oneself (OR = 1.87, 95% CI = 1.12
      3.12) proved to be predictive in multivariate analyses. CONCLUSIONS: This
      constellation of chronic medical conditions and functional disabilities is very
      different from those reported to be associated with depressive symptoms in older
      non-Hispanic White and African Americans, and appears to comprise those
      conditions most associated with substantial physical impairment, pain, and
      discomfort.

PMID- 9597052
TI  - Tolerability of alpha-blockade with doxazosin as a therapeutic option for
      symptomatic benign prostatic hyperplasia in the elderly patient: a pooled
      analysis of seven double-blind, placebo-controlled studies.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disorder in males, and
      its incidence increases with age. Safety results from trials with doxazosin
      therapy in elderly patients were collated and described. METHODS: Safety data
      were collated from seven completed multicenter, double-blind, placebo-controlled
      studies of doxazosin in the treatment of BPH in older patients and analyzed
      according to age group (< 65 and > or = 65 years) and blood pressure status.
      RESULTS: Data for 341 patients aged > or = 65 years (217 normotensive, 124
      hypertensive) and 322 patients aged < 65 years (207 normotensive, 115
      hypertensive) were available. In normotensive subjects a statistically
      nonsignificant smaller percentage of elderly patients reported adverse events
      than younger patients in both doxazosin (42% compared with 47%) and placebo (38%
      compared with 44%) groups. The most common adverse events were fatigue, headache,
      and dizziness whereas withdrawals due to adverse events were 6% (elderly) and 7%
      (younger) for doxazosin patients and 9% and 5% for placebo patients,
      respectively. In hypertensive patients 43% of elderly doxazosin patients reported
      adverse events compared with 30% of elderly placebo patients, the most common
      events in both groups being dizziness, headache, fatigue, and dyspnea. Incidence
      of withdrawal due to adverse events was 11% with doxazosin and 4% with placebo.
      Very few serious adverse events were reported throughout these trials in any
      group. Nonsignificant reductions in mean blood pressure were seen in all
      normotensive patients. Fewer elderly patients had a clinically significant
      reduction in blood pressure than younger patients (26% vs 30%, respectively).
      CONCLUSIONS: These studies show doxazosin to be equally well tolerated in young
      and old, normotensive and hypertensive patients with BPH.

PMID- 9597051
TI  - Preferences of elderly men for prostate-specific antigen screening and the impact
      of informed consent.
AB  - BACKGROUND: Use of the prostate-specific antigen (PSA) as a screening test
      remains highly controversial, particularly in older men. This study was
      undertaken to assess the impact of information on the preferences of older men
      for such screening. METHODS: The elderly cohort (age > or = 65 years) of a larger
      randomized trial was studied to determine the effect of a 3-minute scripted
      informational intervention on primary care patients' interest in PSA screening
      and on potential predictors of screening interest. RESULTS: Informed patients
      were significantly less interested in screening than were uninformed patients (p
      = .006). Informed patients considered PSA screening to be significantly less
      efficacious than did uninformed patients (p = .004), but among both uninformed
      and informed patients, perceived efficacy correlated with interest in screening
      (multivariate OR 2.3, 95% CI 1.5-3.8 for uninformed patients; OR 2.2, 95% CI 1.3
      3.9 for informed patients). Perceived seriousness of prostate cancer predicted
      interest in screening among uninformed patients (OR 1.8, 95% CI 1.3-2.6), but not
      among informed patients. Informed patients who were married were less interested
      in screening than those who were single, divorced, or widowed (OR 0.3, 95% CI .08
      0.9). Marital status did not predict screening interest among uninformed
      patients. CONCLUSIONS: Involving elderly patients in the decision whether to
      screen with the PSA by providing them with information leads to a significant
      reduction in interest in such screening. Factors that appear to influence the
      screening preferences of informed elderly patients include perceived efficacy of
      screening and marital status, whereas uninformed patients are more likely to
      weigh the perceived seriousness of prostate cancer in their screening decision.

PMID- 9597053
TI  - Does artificial enteral nutrition prolong the survival of institutionalized
      elders with chewing and swallowing problems?
AB  - BACKGROUND: There is a lack of prognostic data regarding tube feeding of
      institutionalized elderly people. The objective of this study was to determine
      the impact of feeding tubes on the survival of nursing home residents with
      chewing and swallowing problems, and to follow the course of the tube-fed
      residents over one year. METHODS: We conducted a cohort study with 12-month
      follow-up using Minimum Data Set resident assessments from 1991. Participants
      included 5,266 nursing home residents over the age of 65 with chewing and
      swallowing problems living in 272 Washington state nursing homes. Residents who
      had a feeding tube were identified. Baseline clinical characteristics and 12
      month survival were compared for residents with and without feeding tubes. The
      proportion of tube-fed residents who became tube-free during the follow-up period
      was determined, and clinical features that predicted this outcome were examined.
      RESULTS: Among the residents with chewing and swallowing problems, 10.5% had a
      feeding tube. After adjusting for potential confounding covariates, tube-fed
      residents had a significantly higher one-year mortality rate than those without
      feeding tubes (risk ratio, 1.44; 95% CI, 1.17-1.76). Of the 430 residents with
      feeding tubes who survived the follow-up period, 25.1% became free of a feeding
      tube. Age less than 87 years was associated with a significantly greater
      likelihood of becoming tube-free (odds ratio, 1.66; 95% CI, 1.03-2.6).
      CONCLUSIONS: Residents selected for feeding tube placement have poorer survival
      after one year than residents who are not tube-fed. However, the feeding tubes
      are removed in a significant proportion of residents who survive one year.
      Residents with a potentially reversible condition, for whom the feeding tubes are
      a temporary intervention, need to be identified.

PMID- 9597054
TI  - Body fat and skeletal muscle mass in relation to physical disability in very old
      men and women of the Framingham Heart Study.
AB  - BACKGROUND: Low muscle mass has been assumed to be associated with disability,
      but no studies confirming this association have been published. High body weight
      and high body mass index, both rough indicators of body fatness, have been shown
      to increase the risk for disability; however, the specific role of body fatness
      has not been studied. METHODS: The relations of skeletal muscle mass and percent
      body fat with self-reported physical disability were studied in 753 men and women
      aged 72 to 95 years. Cross-sectional data from biennial examination 22 (1992
      1993) of the Framingham Heart Study were used. Body composition was assessed by
      dual-energy x-ray absorptiometry. Disability was scored as any versus none on a 9
      item questionnaire. RESULTS: Total body and lower extremity muscle mass were not
      associated with disability in either men or women. However, a strong positive
      association between percent body fat and disability was observed. The odds ratio
      for disability in those in the highest tertile of body fatness was 2.69 (95%
      confidence interval 1.45-5.00) for women and 3.08 (1.22-7.81) for men compared to
      those in the lowest tertile. The increased risk could not be explained by age,
      education, physical activity, smoking, alcohol use, estrogen use (women only),
      muscle mass, and health status. Analyses restricting disability to mobility items
      gave similar results. CONCLUSIONS: In contrast to current assumptions, low
      skeletal muscle mass was not associated with self-reported physical disability.
      Persons with a high percent body fat had high levels of disability. Because it
      cannot be ruled out that persons with low skeletal muscle mass dropped out
      earlier in the study, prospective studies are needed to further assess the
      relationship between body composition and physical disability.

PMID- 9597055
TI  - Response (re-)programming in aging: a kinematic analysis.
AB  - BACKGROUND: Age-related motor slowing may reflect either motor programming
      deficits, poorer movement execution, or mere strategic preferences for online
      guidance of movement. We controlled such preferences, limiting the extent to
      which movements could be programmed. METHODS: Twenty-four young and 24 older
      adults performed a line drawing task that allowed movements to be prepared in
      advance in one case (i.e., cue initially available indicating target location)
      and not in another (i.e., no cue initially available as to target location).
      Participants connected large or small targets illuminated by light-emitting
      diodes upon a graphics tablet that sampled pen tip position at 200 Hz. RESULTS:
      Older adults had a disproportionate difficulty initiating movement when prevented
      from programming in advance. Older adults produced slower, less efficient
      movements, particularly when prevented from programming under greater precision
      requirements. CONCLUSIONS: The slower movements of older adults do not simply
      reflect a preference for online control, as older adults have less efficient
      movements when forced to reprogram their movements. Age-related motor slowing
      kinematically resembles that seen in patients with cerebellar dysfunction.

PMID- 9597056
TI  - Determinants of psychomotor speed among 61 pairs of adult male monozygotic twins.
AB  - BACKGROUND: Declining psychomotor speed is an indicator of the aging process, and
      it is influenced by genetics and environmental factors. The present study
      examined the relative effects of familial aggregation (reflecting a combination
      of genetics and early environmental influences), and occupational, lifestyle, and
      health factors on psychomotor speed. METHODS: Hand and foot psychomotor speed was
      studied with 61 pairs of monozygotic male twins aged 35-67 years from the
      population-based Finnish Twin Cohort. The determinants of visual simple and
      choice reaction times were analyzed with multiple regression analysis. RESULTS:
      Familial aggregation, reflecting genetic influences and shared environmental
      effects, explained in mean 47% of decision times, 31% of movement times, and 37%
      of response times (decision time and movement time combined). Age, cardiovascular
      morbidity, lifetime vigorous and frequent exercise participation, and mean
      lifetime daily hours sitting at work explained 0-19% of hand psychomotor speed
      and 0-10% of foot speed, depending on the outcome. The predicted increase in
      decision times due to the presence of cardiovascular morbidity was 11-35 ms. The
      predicted increase for hand and contralateral foot response times between ages 45
      and 55 was 18-41 ms. Smaller effects were noted for each year of strenuous
      exercise and each hour/day of average lifetime sitting at work. CONCLUSIONS:
      Results indicate that cardiovascular status, age, strenuous exercise, and work
      play a role in psychomotor speed, but a rather minor one. In contrast, genetic
      and shared early environmental influences as revealed from familial aggregation
      were relatively strong, yet a major proportion of the variability in psychomotor
      speed remained unexplained.

PMID- 9597057
TI  - Age, period, and cohort effects on physical activity among elderly men during 10
      years of follow-up: the Zutphen Elderly Study.
AB  - BACKGROUND: Data regarding the nature of change in physical activity as elderly
      people become progressively older are scarce. The present study describes changes
      in the physical activity pattern of a cohort of elderly Dutch men between 1985
      and 1995. METHODS: Self-reported physical activity was assessed with a reliable
      and valid questionnaire designed for retired men. In 1985, 863 men (aged 65-84
      years) were examined, in 1990, 520 surviving men, and in 1995, 343 men. Three
      analytical perspectives (cross-sectional, longitudinal, and time-series) were
      used concurrently to untangle effects of aging, period, and birth cohort on the
      10-year change in physical activity. RESULTS: Mean total time spent on physical
      activity decreased by 33% (28 min/day) during 10 years of follow-up. Time spent
      on bicycling, gardening, and total activity decreased with aging. A period effect
      was observed for time spent on bicycling and total activity in 1990 (increase)
      and gardening in 1995 (decrease). No differences in physical activity between
      birth cohorts were observed. Time spent on walking remained stable during follow
      up, but its relative contribution to total time spent on physical activity
      increased with aging. The pattern of change in total activity was not affected by
      functional status. CONCLUSIONS: Mean total time spent on physical activity by
      elderly men clearly decreased during follow-up. This could not be fully explained
      by declining functional status, but was partly explained by aging. In contrast to
      other physical activity parameters, time spent on walking was not affected by
      aging. These results suggest an increasingly restrictive physical activity
      pattern with aging.

PMID- 9597058
TI  - Spatial-temporal analysis of mobility over the adult age range using the Postural
      Locomotor-Manual Test.
AB  - BACKGROUND: Mobility measurements were performed on healthy adult subjects to
      investigate changes over the adult age range and to obtain reference values.
      METHODS: Ninety-five males (19-90 years, mean 58.2) and 122 females (19-90 years,
      mean 51.8) were measured using the commercially available Postural-Locomotor
      Manual Test (PLM-test). Subjects are required to perform a standard maneuver that
      is recorded using an optoelectronic technique. RESULTS: Older subjects carried
      out all phases of the maneuver more slowly than younger subjects. At about the
      age of 50 years, females showed a more rapid slowing down. Males showed a more
      gradual decrease over the adult age range. CONCLUSION: The PLM-test provides a
      fairly simple noninvasive method of assessing motor performance. However, it is
      important to separate male and female data in the determination of reference
      values.

PMID- 9597059
TI  - Education at the crossroads: which paths for the DPT?

PMID- 9597060
TI  - Association between characteristics of locomotion and accomplishment of life
      habits in children with cerebral palsy.
AB  - BACKGROUND AND PURPOSE: "Handicap situation" is defined in the literature as "a
      disruption in the accomplishment of a person's life habits (activities of daily
      living and social roles)." The purpose of this study was to determine the
      strength of association between various types of locomotion and the
      accomplishment of life habits, which is an indicator of the occurrence of
      handicap situations in children with cerebral palsy. SUBJECTS: Ninety-eight
      children with cerebral palsy, aged 5 to 17.8 years (mean = 10.5, SD = 3.5), were
      recruited. METHODS: The Life Habits Assessment was used to evaluate handicap
      situations in activities of daily living and social roles. Types of locomotion,
      the Pediatric Functional Independence Measure (locomotion section), and 2 tests
      representing functional activities (walking speed and stair climbing) were used
      as characteristics of locomotion. RESULTS: Locomotion capabilities were
      associated with the accomplishment of activities of daily living and social
      roles. Performance in variables related to locomotion, number of associated
      problems, and type of cerebral palsy explained 17% to 74% of the total variance
      in accomplishment of life habits in children who walked without technical aids.
      CONCLUSION AND DISCUSSION: The results suggest that locomotion might influence
      the accomplishment of life habits. Other factors, however--such as environmental
      barriers--should also be examined to determine their impact on the occurrence of
      handicap situations.

PMID- 9597061
TI  - The use of therapeutic ultrasound by physical therapists in Dutch primary health
      care.
AB  - BACKGROUND AND PURPOSE: The purposes of this study were to describe the use of
      ultrasound by Dutch physical therapists and to address the question of whether
      this use is what would be considered correct. SUBJECTS AND METHODS: Physical
      therapists in the Dutch primary health care system gathered data on 17,201
      patients, addressing reasons for referral, treatment goals (in terms of
      impairments and disabilities), and physical therapy interventions. Patients
      treated with ultrasound (n = 3,959) were compared with a reference group of
      patients who were not treated with ultrasound (n = 13,242). RESULTS: Physical
      therapists applied ultrasound for soft tissue injuries of recent onset, mainly
      aiming to reduce pain and swelling. Ultrasound was used in all phases of
      treatment and was not restricted to the first 3 weeks of treatment. Ultrasound
      was combined relatively infrequently with exercise and relatively frequently with
      massage. CONCLUSION AND DISCUSSION: Regarding the indications for referral and
      treatment goals chosen, the actual use of ultrasound corresponds to assumptions
      about expected use. The timing of its application and the combination with other
      forms of therapy do not correspond in all aspects to the assumptions made.

PMID- 9597062
TI  - The ecological relevance of the Test of Infant Motor Performance elicited scale
      items.
AB  - BACKGROUND AND PURPOSE: The Test of Infant Motor Performance (TIMP) is a new test
      of motor and postural control for infants under 4 months of age. The purpose of
      this study was to examine the relationship between the environmental demands
      placed on infants in daily life and the demands placed on infants during
      administration of the TIMP Elicited Scale items. SUBJECTS: Twenty-two preterm and
      full-term infants and their caregivers participated. The infants were evenly
      divided into groups at low and high medical risk for developmental disability.
      METHODS: The infants were videotaped while being handled by their caregiver
      during undressing, bathing, dressing, and 5 minutes of playing in their natural
      setting (home or hospital). Each videotape recording was analyzed for the
      environmental demands that were placed on the infant during caregiving. Demands
      were coded according to predefined definitions, which represented descriptions
      for administering TIMP items. Interrater agreement for coding of observations
      ranged from 80% to 96%. RESULTS: Environmental demands that corresponded to 23 of
      the 25 TIMP items were observed during caregiving activities. The number of
      environmental demands placed on the infants during caregiving that corresponded
      to the 25 TIMP Elicited Scale items ranged from 16% to 68% of the items (mean =
      37%). The mean rate of all environmental demands placed on the infants was 3.23
      per minute, and the mean rate of demands that corresponded to TIMP items was 1.58
      per minute. CONCLUSION AND DISCUSSION: Approximately 50% of all environmental
      demands placed on the infants during caregiving corresponded to TIMP Items, and
      98% of TIMP Elicited Scale Items Corresponded to the observed environmental
      demands. The demands placed on infants during administration of the TIMP appear
      representative of typical environmental demands.

PMID- 9597063
TI  - Hip abductor muscle activity as subjects with hip prostheses walk with different
      methods of using a cane.
AB  - BACKGROUND AND PURPOSE: Using a cane held contralateral to a prosthetic hip is
      presumed to be an effective way to reduce the demands on the hip abductor (HA)
      muscles and, therefore, the forces on the implant. In this study, surface
      electromyographic (EMG) activity was measured from the HA muscles to test this
      notion. SUBJECTS: Twenty-four active subjects (9 female, 15 male) with unilateral
      prosthetic hips were tested. The subjects, aged 40 to 86 years (mean = 63.3, SD =
      10.7), were not regular cane users. METHODS: Surface EMG activity and cane force
      were analyzed while the subjects walked with the cane held (1) contralateral to
      the prosthesis (CL-CANE), (2) ipsilateral to the prosthesis (IL-CANE), and (3)
      contralateral to the prosthesis with instructions for the subject to push with a
      "near-maximal effort" (CL-CANE+). RESULTS: Only the following conditions showed a
      change in HA muscle EMG activity as compared with not using a cane: CL-CANE = 
      31.1%, CL-CANE+ = -42.3%. CONCLUSION AND DISCUSSION: Holding the cane
      contralateral to the prosthetic hip appears to be an effective method of reducing
      demands on the HA muscles.

PMID- 9597064
TI  - Relationship between standing posture and stability.
AB  - BACKGROUND AND PURPOSE: This study determined whether persons with stability
      impairments have postural aberrations. We investigated whole-body posture and its
      relationship to center-of-gravity (COG) stability. SUBJECTS: Data from 27
      subjects with vestibular hypofunction and 26 subjects without vestibular
      impairment were analyzed. METHOD: An optoelectronic full-body system measured
      kinematics. Force plates measured ground reaction forces while subjects stood
      with their feet 30 cm apart and eyes open and with their feet together and eyes
      closed. RESULTS: The subjects with vestibular hypofunction demonstrated less
      stability than the subjects without impairment, but there were no postural
      differences. Subjects with vestibular hypofunction had more weight on the left
      lower extremity during standing with feet apart. In all subjects in both groups,
      during standing with feet apart, the COG was anterior to the ankle, knee, back,
      and shoulder and posterior to the hip and neck. Subjects had an anterior pelvic
      tilt, extended trunk and head, right laterally flexed trunk and pelvis, and
      flexed knees. With their feet together, subjects increased their anterior pelvic
      tilt; trunk, head, and knee flexion; and anterior COG position. CONCLUSION AND
      DISCUSSION: Posture and stability had a low correlation. Subjects with bilateral
      vestibular hypofunction did not demonstrate a forward head or backward trunk
      lean, as has been reported anecdotally. Changing from standing with feet apart to
      feet together increased whole-body movement patterns to control standing
      stability.

PMID- 9597065
TI  - Examination and management of a patient with tarsal coalition.
AB  - The purpose of this case report is to illustrate how the literature can be used
      to guide clinical decisions related to a relatively uncommon pathological
      condition of the foot. This case report describes the approach used to examine
      and treat a 14-year-old boy referred by a physician for physical therapy with a
      diagnosis of peroneal spastic flatfoot (PSFF). Peroneal spastic flatfoot is a
      syndrome typically characterized by limited tarsal joint motion, a clonus
      response of the evertors, and a pes planus deformity. The patient reported having
      a limp for several years, but he said he was pain-free until he had an inversion
      injury of his foot. Because the physical therapists had not seen a patient with a
      diagnosis of PSFF, they reviewed the literature related to PSFF. They describe
      how their review enhanced their understanding of PSFF and how PSFF is related to
      the diagnosis of tarsal coalition, a pathological condition eventually identified
      in this child. Following 5 unsuccessful physical therapy sessions, they referred
      the patient to another physician who diagnosed a talocalcaneal coalition, a type
      of tarsal coalition.

PMID- 9597066
TI  - EMG onset timing.

PMID- 9597067
TI  - Discography 2000.
AB  - Discography is an invasive and controversial procedure that can be used as a
      complementary test to MR imaging or a CT myelogram prior to surgery. The
      examination may be performed in the prone or decubitus position. Pain provocation
      is the most important part of the examination. CT discography provides valuable
      information regarding pattern, number, extent, and degree of annular tears.
      Correlation of discography with cross-sectional imaging studies is reviewed and
      the surgical outcome is discussed.

PMID- 9597068
TI  - Diagnostic and therapeutic features of facet and sacroiliac joint injection.
      Anatomy, pathophysiology, and technique.
AB  - A diagnosis of exclusion facet syndrome is considered one of the many genuine
      causes of low back pain. Using careful patient selection, percutaneous facet
      joint block is a useful diagnostic and therapeutic procedure in the management of
      lumbar facet syndrome. Sacroiliac joint syndrome appears to be a more tangible
      entity diagnostically and more amenable to injection. This article addresses the
      anatomy, pathophysiology, and salient radiographic features of the apophyseal
      joint, and describes the procedures and techniques for facet as well as
      sacroiliac joint injection.

PMID- 9597069
TI  - Percutaneous epidural and nerve root block and percutaneous lumbar sympatholysis.
AB  - Epidural steroid injections and selective nerve root blocks currently are
      considered standard techniques in the diagnosis and treatment of back pain. The
      targeted epidural and perineural steroid injection with nerve block is a new
      technique that combines an epidural steroid injection and a nerve block.
      Radiologists are best suited for performing these procedures because of their
      training and skills in fluoroscopy and needle procedures.

PMID- 9597070
TI  - Nuances in percutaneous discectomy.
AB  - This article presents an update of the field of percutaneous discectomy and a
      perspective as to where percutaneous discectomy currently fits in the treatment
      of patients with herniated discs. The future of minimally invasive disc surgery
      is also entertained, and a novel approach to lumbar disc surgery is presented.

PMID- 9597071
TI  - Percutaneous vertebroplasty with polymethylmethacrylate. Technique, indications,
      and results.
AB  - Percutaneous vertebroplasty with acrylic cement consists of injecting
      polymethylmethacrylate into vertebral bodies destabilized by osseous lesions. The
      aim is to obtain an analgesic effect by reinforcing lesions of the spine. The
      major indications are vertebral angiomas, osteoporotic vertebral crush syndromes,
      and malignant spinal tumors. The clinically significant complications occur
      predominantly in patients with spinal metastatics, but in the great majority of
      cases they resolve with medical treatment.

PMID- 9597072
TI  - Interventional radiology with laser in bone and joint.
AB  - Laser energy is able to ablate, coagulate, and vaporize tissues. Its
      transmissibility in thin optical fibers makes it an ideal tool for use in
      percutaneous procedures. This article describes two applications in
      interventional musculoskeletal radiology. In percutaneous laser disc
      decompression the laser source is used to vaporize a small portion of the nucleus
      pulposus. In interstitial laser photocoagulation of osteoid osteoma the laser
      energy is used to coagulate and destroy the tumor by direct heating.

PMID- 9597073
TI  - Percutaneous removal of osteoid osteoma.
AB  - In most cases, osteoid osteomas can be removed through a percutaneous approach.
      The authors report their experience of percutaneous removal of osteoid osteomas
      under CT guidance. The literature on percutaneous treatments of osteoid osteomas
      is reviewed. The respective advantages of percutaneous removal and percutaneous
      destruction of the nidus using thermocoagulation or interstitial laser
      photocoagulation are discussed.

PMID- 9597074
TI  - Biopsies of the musculoskeletal system.
AB  - Percutaneous biopsies of musculoskeletal lesions are a safe, economical, and
      reliable method of obtaining a diagnosis. Most of these biopsies are done under
      CT guidance, but fluoroscopy is an alternative. Conditions that can be discovered
      through percutaneous biopsies include metastases, primary benign tumors,
      infection, and metabolic disease. Experience with invasive procedures and with
      imaging equipment are the requirements for a physician interested in performing
      these biopsies.

PMID- 9597076
TI  - Percutaneous treatments of painful shoulder.
AB  - Percutaneous treatments are useful in two, frequent, painful conditions involving
      the shoulder. In frozen shoulder syndrome, distention arthrography with intra
      articular injection of steroid is used to provide pain relief and to improve
      joint motion. In rotator cuff tendon calcifications, needle aspiration of
      calcific deposits is used to treat pain. Surgery should be restricted to failures
      of needle aspiration. The techniques of these procedures are described and their
      results are reported.

PMID- 9597075
TI  - Intraosseous cyst injection.
AB  - Unicameral and aneurysmal bone cysts are benign lesions, but they often require
      treatment to prevent pathologic fractures. Percutaneous therapeutic techniques
      have been developed because they are less aggressive than surgery. A radio
      orthopedic consensus is required to choose a percutaneous method rather than a
      surgical procedure, especially in children.

PMID- 9597077
TI  - Ultrasound-guided interventional procedures in the musculoskeletal system.
AB  - Ultrasound is a low-cost, nonionizing, readily available diagnostic technique for
      the evaluation of tendons, muscles, soft tissue masses, cysts, and other fluid
      collections. Ultrasound is also a valuable tool for guiding a variety of
      musculoskeletal interventions. Procedures that can be performed under ultrasound
      guidance include aspiration of fluid for analysis, injection for medication,
      decompression of cysts, drainage of abscess and hematoma, biopsy, treatment of
      calcified tendinitis, and foreign body retrieval.

PMID- 9597078
TI  - Is the prion structure solved?
AB  - We report here on the current knowledge on the nature of the scrapie agent or
      prion. Several lines of evidence suggest that the abnormal isoform of prion
      protein (PrP) is crucial for scrapie infectivity while evidence that PrP is also
      a part of the entire particle of the scrapie agent (prion) is much weaker. There
      is no doubt, however, that conformational changes (transitions from alpha-helical
      into beta-pleated structures) of PrP underlay scrapie pathogenesis. In view of
      the notorious puzzling nature of the scrapie agent, the electron microscopic
      search for the ultrastructural correlate of it is still warranted. Thus, we
      discuss the nature of tubulovesicular structures (TVS), the only diseases
      specific particles known so far and the association between TVS and PrP fibrils
      which was recently discovered.

PMID- 9597079
TI  - Immunological adjuvants and their modes of action.
AB  - New adjuvant formulations contain a vehicle, which carries antigens to antigen
      presenting cells. Examples of vehicles are liposomes, immune-stimulating
      complexes and microfluidized squalene-in-water emulsions. Adjuvant formulations
      may contain immunomodulators, which augment cytokine production, such as a
      synthetic muramyl dipeptide analog or monophosphoryl lipid A. In a primary
      cascade of cytokine production at the site of antigen + adjuvant injection, TNF
      alpha promotes the migration of dendritic cells (DC) to lymphoid tissues while GM
      CSF accelerates the differentiation of DC into efficient presenters of antigens
      to T cells. Adjuvants also up-regulate a secondary cascade of cytokines in
      lymphoid tissues responding to antigenic stimulation: IL-12 augments the
      production of IFN-gamma, which favors the production of antibodies of protective
      isotypes (IgG2a in the mouse). Thus adjuvants can regulate immune responses
      qualitatively as well as quantitatively. Adjuvant formulations can also activate
      complement, generating C3d, which binds CD21 on follicular dendritic cells (FDC)
      and B cells. FDC targeting favors the generation of B lymphocyte memory, which is
      important for vaccination.

PMID- 9597080
TI  - Molluscan immune defenses.
AB  - The interest of marine invertebrates as food resources provides a major interest
      to study molluscan immunity for better understanding of the host response to
      pathogens. Molluscs possess a natural immunity formed by anatomical and chemical
      protective barriers that prevent damage of the underlying tissues, body fluid
      losses and the infections of pathogenic microorganisms and parasites. The main
      physical barrier is shell and mucus which cover the soft body of molluscs. The
      integrity of body coverings is supported by blood clotting and wound healing. The
      internal defense mechanisms of molluscs involve such cellular reactions as:
      phagocytosis, nodule formation, encapsulation, pearl formation, atrophy, necrosis
      and tissue liquefaction. Granular hemocytes are the most numerous cell type of
      molluscan blood active in cellular defenses. Invaders small in size are
      eliminated by phagocytosis in which participate lectins and products of
      prophenyloxidase system activation. Numerous and large intruders are eliminated
      by nodule formation or encapsulation, either cellular or humoral. Humoral
      components of molluscan immunity are formed by lysozyme activity, lectins and the
      phenyloxidase system. Up to now the role of mercenenes, paolins, acute phase
      reactants, alpha 2-macroglobulins and multifunctional binding proteins with anti
      protease activity is not well clarified yet. Research prospects on the field of
      molluscan immunology should essentially be devoted to study cellular defense
      functions and humoral effectors to select pathogen-resistant molluscs. This aim
      could also be achieved by the identification and characterization of immune genes
      which are candidates for molluscs genetic transformation.

PMID- 9597081
TI  - Rhythms of immunity.
AB  - Rhythms of daily activity are found in all vertebrate species, some of them being
      diurnal (like humans, dogs, pigeons), others--nocturnal (like mice, rats and
      bats). Some species undergo very pronounced seasonal changes, as they hibernate
      in the winter or mate only at the specific seasons. The main regulator (a clock
      and a calendar) for daily and seasonal rhythms is the periodicity of the external
      light-darkness, reflected by the periodicity of melatonin secretion from the
      pineal gland, which is inhibited by light and induced during the darkness. In
      contrast to melatonin which peaks during the night both in diurnal and noctural
      species, the cyclicity of other hormones and several immune parameters correlates
      with the pattern of the animal locomotor activity-resting. The immune parameter
      that peaks at one time of day for a diurnal species peaks about 12 h later for a
      nocturnal one. Various immune parameters peak at various time points,
      anticipating an encounter with pathogens during the period of activity while
      energetically expensive resolution of the immune response during the resting.
      Daily and seasonal cyclicity of the immune functions are temporally integrated
      with other physiologic and behavioral processes and all of them are regulated and
      coordinated with daily and seasonal changes of an external environment by the
      neuroendocrine homeostatic system.

PMID- 9597082
TI  - Regulation of cytokine production by eicosanoids and nitric oxide.
AB  - Cytokines are widely regarded as regulatory molecules of inflammatory and immune
      reactions. Nevertheless, the details of functioning of the complex cytokine
      network are not yet fully understood. Recent data indicate that eicosanoids,
      primarily the products of the inducible form of cyclooxygenase (COX-2), are
      involved in the regulation of cytokine production. We have shown that
      prostaglandins of E series are no longer only suppressor molecules but they
      selectively up- or down-regulate the cytokine production. Similarly, nitric oxide
      (NO) generated in activated immune cells by inducible isoform of nitric oxide
      synthase (iNOS), is considered to be an immunoregulatory molecule. In this
      article we present a new concept of interactions between cytokines, eicosanoids
      (prostaglandins and leukotrienes) and NO. Finally, the impact of these molecules
      on the regulation of the immune system is discussed.

PMID- 9597083
TI  - Immunological status of septic and trauma patients. I. High tumor necrosis factor
      alpha serum levels in septic and trauma patients are not responsible for
      increased mortality; a prognostic value of serum interleukin 6.
AB  - The aim of this study was to monitor plasma interleukin 6 (IL-6), and tumor
      necrosis factor alpha (TNF-alpha), levels in patients with sepsis, septic shock
      and multiple organ dysfunction syndrome admitted to the intensive care unit. The
      patients obtained adequate supportive therapy. Plasma samples were taken upon
      admission, then on days 1, 2, and 5 following admission. IL-6 and TNF-alpha
      levels were determined using bioassays (7TD1 and WEHI-164.13 indicator cell
      lines, respectively). The results showed that the kinetics of the cytokine
      release in septic patients differed significantly between survivors and
      nonsurvivors. In survivors IL-6 concentrations were initially high, fell down
      rapidly on day 1 after admission, and persisted very low throughout the
      monitoring time. In contrast, relatively low IL-6 levels in the nonsurvivors,
      registered upon admission, rose significantly with peak values on day 3 of
      observation, declining thereafter. TNF-alpha levels were initially higher in
      survivors than in nonsurvivors, declined on day 1 following admission, and on day
      5 they were higher than the initial values. In nonsurvivors, on the other hand,
      the starting concentrations of TNF-alpha were much lower than in survivors with a
      peak on day 3 with a tendency to fall on day 7. The profiles of cytokine
      production by traumatic patients (90% survivors) revealed low and progressively
      diminishing levels of IL-6, contrasting with constantly increasing concentrations
      of TNF-alpha within the monitoring period. We conclude that high IL-6 levels in
      septic patients accompanied by high TNF-alpha levels may indicate bad prognosis.
      In contrast, rapidly diminishing serum IL-6 levels, even in the presence of high
      TNF-alpha levels, could indicate a very good chance for survival. Similar
      conclusion can be drawn from the monitoring of cytokine production in traumatic,
      nonseptic patients since almost all of them recovered. We also speculate that TNF
      alpha presence in circulating blood is essential for regeneration of tissues and
      wound healing.

PMID- 9597085
TI  - Isoprinosine and levamisole as stimulators of interferon production in blood
      leukocytes of patients with alcoholic liver cirrhosis.
AB  - Blood leukocytes of 16 patients with alcoholic liver cirrhosis and 18 healthy
      controls were induced for interferon (IFN) production by phytohemagglutinin (PHA)
      and concanavalin A (ConA) in the presence or absence of isoprinosine and
      levamisole at concentrations of 10 micrograms/ml and 1 ng/ml. This interferon was
      neutralized in 87-95% by anti-HuIFN-gamma monoclonal antibodies. In the presence
      of the drugs the IFN-gamma production was enhanced, however, IFN-gamma titers
      yielded from leukocytes of cirrhotic patients were still below the titers
      observed in stimulated and unstimulated blood leukocytes of healthy controls. For
      example, IFN titers induced by PHA in the presence of levamisole (1 ng/ml) in
      cirrhotic patients were 2.5 times lower (20.2 +/- 11.1 U/ml) in comparison to
      healthy subjects (50.6 +/- 27.3 U/ml).

PMID- 9597084
TI  - Modulating effect of interleukin 2 therapy on interferon production by blood
      leukocytes of patients with minimal residual hematological disease.
AB  - This study was designed to investigate the effect of 1.8 x 10(6) U/day
      interleukin 2 (IL-2) therapy on interferon (IFN) production. Patients enrolled in
      the study suffered from multiple myeloma (MM), Hodgkin's disease (HD) and non
      Hodgkin lymphoma (NHL). All of them were in remission after chemotherapy or
      radiotherapy. Results indicated that IL-2 given subcutaneously at a dose of 1.8 x
      10(6) U/day for 3 weeks induced IFN-gamma in serum of patients and caused a
      prolonged effect on the ability of blood leukocytes to produce IFN-gamma after
      stimulation in vitro by mitogen phytohemagglutinin (PHA). Such enhancement of IFN
      gamma production may be beneficial for antitumor immune response. Low-dose IL-2
      therapy was well tolerated by all patients and side effects not exceeding II
      grade of toxicity according to WHO scale were observed. Five patients with MM
      have relapsed 3-10 months after cesation of IL-2 therapy but 15 patients 18
      months after therapy were in complete remission.

PMID- 9597086
TI  - Changes in the phagocytic cells in children treated with continuous ambulatory
      peritoneal dialysis.
AB  - Children on continuous ambulatory peritoneal dialysis (CAPD) in endstage renal
      failure are highly exposed to peritonitis. Peritoneal macrophages (PM) and blood
      neutrophils (PMNC) are the first line of defense against invading microbes. This
      study was undertaken for assessing surface receptors expression on PM and PMNC
      and to check their ability to phagocytosis and killing of bacteria. We have found
      that in spite of the decreased number of PM in dialysate fluid their viability
      and activity significantly increased during CAPD. Moreover, higher number of PM
      expressed CD16 and CD35 antigens (FcRIII and C3bR, respectively) in comparison
      with the results observed at CAPD onset. The number of PMNC expressed of these
      two antigens in uremic children blood were significantly lower in comparison with
      healthy control. The number of CD16 positive cells increased under influence of
      CAPD only temporarily. CAPD caused improvement of phagocytosis and intracellular
      killing of bacteria by PM but not by PMNC. There is discussed here influence of
      uremia and CAPD on surface antigens, function of phagocytes as well as renewal of
      PM during CAPD.

PMID- 9597087
TI  - Eosinophil cationic protein in serum of corticosteroid-sensitive and resistant
      bronchial asthma.
AB  - Theories for the inflammatory basis of bronchial asthma are presented. The
      phenomenon of corticosteroid resistance (CR) in bronchial asthma is also
      discussed. Resistance to corticosteroids, which occurs in about 5% patients with
      moderate and severe asthma, presents still an important diagnostic and
      therapeutical problem. In addition, present opinions on the role of eosinophils
      in the allergic bronchial inflammation were analyzed. The aim of this study was
      to monitor serum eosinophil cationic protein (ECP) level in asthma patients,
      sensitive and resistant to glucocorticosteroids (GCS), before and after
      prednisolone treatment. The resistance to steroids was determined, based on the
      oral prednisolone test according to Carmichael and vasoconstriction assay
      according to Stoughton and McKenzie. In the group of corticosteroid-sensitive
      (CS) asthmatic patients a statistically significant decrease of ECP level was
      observed, after 10 day administration of prednisolone in a daily dose of 20 mg,
      which was associated with a meaningful increase of FEV1 value. On the other hand,
      the level of ECP in the serum of patients resistant to corticosteroids, although
      also decreased under influence of prednisolone, was not correlated with the
      increase of FEV1 value.

PMID- 9597088
TI  - Immunological status of patients subjected to cardiac surgery: effect of
      lactoferrin on proliferation and production of interleukin 6 and tumor necrosis
      factor alpha by peripheral blood mononuclear cells in vitro.
AB  - The aim of this investigation was to monitor proliferation and cytokine
      production by peripheral blood mononuclear cells (PBMC) of patients subjected to
      cardiac surgery. Another goal was to establish regulatory effects of lactoferrin
      (LF) on these immune reactions in vitro. PBMC were tested before, during surgery
      and on day 1 and day 8-10 following operation. In control donors, low spontaneous
      and phytohemagglutinin (PHA)-induced proliferation of PBMC, as well as
      lipopolysaccharide (LPS)-induced TNF-alpha secretion was stimulated by LF, but
      high production of this cytokine was inhibited. In patients, the proliferation of
      PBMC and the ability to produce IL-6 TNF-alpha by these cells underwent
      characteristic changes depending on preoperative immune reactivity of patients.
      In general, low, preoperative reactivity of PBMC showed a tendency to increase
      within the monitoring period whereas moderate/high responsiveness was
      diminishing. LF had, in majority of cases, a down-regulatory effect on the
      proliferative response, best pronounced in patients of high/moderate preoperative
      response. Similarly, LF exhibited, in general, an inhibitory effect on LPS
      induced IL-6 production. In terms of TNF-alpha production, a considerable up
      regulatory effect of LF, particularly in low responding patients was of a special
      interest. In summary, we suggest that LF may play a role in lowering the immune
      response of patients to surgery and promoting tissue regeneration.

PMID- 9597089
TI  - Release of tumor necrosis factor alpha and its soluble receptor p55 in clinical
      septic syndrome.
AB  - Tumor necrosis factor alpha (TNF-alpha, cachectine) attracts much clinical
      interest when it looses its primary immune properties and, in the septic
      syndrome, initiates its destructive activity against host tissues. Behaviour of
      TNF-alpha and p55, its soluble receptor (sTNF-R p55), was studied in 50 patients
      with septic syndrome. Their clinical state was assessed by means of the APACHE II
      score. Group I consisted of 23 patients who had survived the infection. Twenty
      seven patients (54%) died, constituting group II. The concentrations of TNF-alpha
      and sTNF-R p55 were determined according to the ELISA method. The obtained
      results were referred to the severity of the patients' clinical state, their
      survival rate, the number of lactates and the quantity of the C-reactive protein
      in blood and the number of blood platelets and neutrophils. It has been
      documented that in septic syndrome patients with poor prognosis the concentration
      of TNF-alpha rises, together with a similar decrease of sTNF-R p55 concentration.
      This relationship is very important for the prognosis in septic syndrome.

PMID- 9597090
TI  - Distribution of apolipoprotein E4 isoform in Alzheimer's disease in Poland.
AB  - Alzheimer's disease (AD) is the most common human progressive dementia linked, in
      its sporadic form, to a common polymorphism within a gene for apolipoprotein E
      (APOE) mapped to chromosome 19. Individuals with APOE 4 isoforms are more prone
      to develop sporadic from of AD than those who carry APOE 2 or APOE 3 alleles. As
      distribution of APOE isoforms in Poland is unknown, we decided to study it in AD
      and control cases. In AD group, three patients (23.1%) were homozygous for APOE
      4, four cases (30.8%) were heterozygous and six cases (46%) carried no APOE 4
      allele. In control group (n-11), only one case (9.1%) was homozygous for APOE 4
      allele, no case was heterozygous for APOE 4 while 10 cases (90.9%) carried no
      APOE 4 alleles. Our results are virtually identical to those reported from
      Western countries.

PMID- 9597091
TI  - Haptoglobin concentration in blood sera of hoofed mammals in captivity.
AB  - There were 151 serum samples of the zoological species of hoofed animals from the
      Bovidae, Cervidae and Equidae families examined for the presence of haptoglobin
      (Hp). In the majority of samples the Hp levels were close to the ones defined in
      the related species of domestic animals (86.49, 52.38 and 69.7% in particular
      families, respectively). In females (13.94% in the Bovidae family, 63.64% in the
      Cervidae, 15% in the Equidae) more often than in males (11.11, 26.32 and 0%,
      respectively) the increased Hp concentrations were found. What is striking it is
      the relatively high frequency of the raised Hp concentrations occurrence in the
      Cervidae sera, which may be connected with the higher responsiveness to the
      factors inducing Hp rise in this family. The contribution of infectious,
      parasitic, stress-inducing factors and injuries is taken into consideration as
      the main cause of the raised levels occurrence in the sera of animals kept in
      zoological gardens. The obtained results suggest the potential usefulness of the
      Hp estimation as a routine examination in the diagnostics of the inflammation in
      wild species of Bovidae and Cervidae as well as in monitoring the animal well
      being in the zoological gardens.

PMID- 9597092
TI  - Some parameters influencing immunoassay of human and horse myoglobins.
AB  - It was noted that human and horse sera as well as human heart and skeletal muscle
      homogenates or extracts distinctly decrease immunoassays of purified myoglobins.
      The assays of homogenate and extract myoglobins could be many times increased by
      precipitation certain proteins with concentrated ammonium sulfate or sodium
      chloride. Also in homogenates and extracts incubated for several days increased
      assays of myoglobins were noted. The obtained results indicate that both
      myoglobins occur in complex with other tissue component(s).

PMID- 9597093
TI  - Mechanism of antigenic variation in Shigella flexneri bacilli. IV. Role of
      lipopolysaccharides and their components in the sensitivity of Shigella flexneri
      1b and its Lac+ recombinant to killing action of serum.
AB  - The effect of lipopolysaccharides (LPS) on the normal bovine serum (NBS)
      bactericidal reactions against mixture of S. flexneri 6713 1b strain and its 3b
      Lac+ recombinant were investigated. The serum killing of S. flexneri strains was
      inhibited, in different degree, by LPS extracted from either organisms. These
      properties were mainly due to LPS molecules; the lipid A fraction showed only low
      anticomplement activity, the polysaccharide fraction inhibited the killing
      activity of NBS in very low degree even at high concentration. These studies
      suggest that LPS composition especially the O-antigen polysaccharide chain
      contributes to the susceptibility of S. flexneri strains to NBS bactericidal
      activity.

PMID- 9597094
TI  - Effect of viral infections on the ability of human endothelium for interferon,
      tumor necrosis factor and interleukin 6 production.
AB  - We have reported that cultured human umbilical cord vein endothelial cells
      (HUVEC) differ from endothelium present on vein surface of organ culture (OC) in
      production of cytokines and susceptibility to viral infections. In this paper we
      present the effect of viral infections on interferon (IFN), tumor necrosis factor
      (TNF), and interleukin 6 (IL-6) production in two culture systems: HUVEC and OC.
      Infection of 24-48 h HUVEC with herpes simplex type 1 (HSV-1) and vesicular
      stomatitis virus (VSV) reduced the amounts of IL-6 and TNF produced in comparison
      to those released spontaneously by uninfected cells. No IFN was detected in media
      from infected and uninfected HUVEC. Limited viral infections of 3-h-HUVEC and OC
      usually diminished their efficiency of IL-6 and TNF production. In the case of IL
      6 synthesis by OC, effect of viral infection depended, however, on the
      constitutive synthesis of the cytokine. When spontaneous production was high (>
      800 U/ml), VSV and HSV-1 infection reduced IL-6 level by 2-50 times; in the case
      of low production (< 150 U/ml) the stimulation effect (2-4 fold) was observed. OC
      released spontaneously some IFN activity (2-32 U/ml). HSV-1 infection of OC
      reduced IFN level, while VSV in single cases slightly upregulated IFN synthesis.

PMID- 9597095
TI  - Metoclopramide and nitrendipine are unable to enhance cytotoxicity of
      mitoxantrone in sensitive and resistant murine leukemias in vivo.
AB  - The influence of metoclopramide and nitrendipine on the antitumor action of
      mitoxantrone (MX) in murine leukemias L1210 and P388 was investigated. These
      agents were administered in combination with MX to mice bearing sensitive or
      resistant leukemias. Mitoxantrone resistant P388 was developed in vivo by
      repeated passages of the tumor to animals treated with suboptimal dose of the
      drug. Survival time of mice receiving combined therapy were not prolonged as
      compared with animals treated with MX alone. Both metoclopramide and nitrendipine
      were unable to overcome MX resistance even partially.

PMID- 9597096
TI  - HIV-protein-mediated alterations in T cell interactions with the extracellular
      matrix proteins and endothelium.
AB  - Recent data point to the immunoregulatory role of extracellular matrix (ECM)
      proteins in the process of T cell activation. We studied the effects of HIV
      proteins on those interactions as well as on endothelial adhesion molecule
      expression. Gp 120 and gp 41 inhibited CD3-triggered T cell co-stimulation by the
      ECM proteins, while Nef was stimulatory. T cell adhesion to the ECM proteins was
      affected in a similar fashion. Furthermore, tat induced E-selectin (but not VCAM
      1 and ICAM-1) endothelial expression. Those findings may be relevant for the
      understanding of immunopathology of AIDS.

PMID- 9597097
TI  - What does it all mean?

PMID- 9597098
TI  - The lateral chest radiograph: is it doomed to extinction?

PMID- 9597099
TI  - Identifying left lower lobe pneumonia at chest radiography: performance of family
      practice residents before and after a didactic session.
AB  - RATIONALE AND OBJECTIVES: The authors sought to determine whether the lateral
      chest radiograph is helpful in identifying left lower lobe pneumonia among
      inexperienced readers. MATERIALS AND METHODS: The authors selected all patients
      who presented to a family practice training program with radiologic and clinical
      evidence of left lower lobe pneumonia (n = 65). They then selected an equal
      number of patients in whom chest radiographs were taken to "rule out pneumonia"
      and were found to be normal. Eight 1st-year family practice residents were asked
      to read the radiographs before and after a didactic session that emphasized
      lateral chest radiograph interpretation. The radiographs were presented under two
      viewing conditions: posteroanterior (PA) only versus PA and lateral. Receiver
      operating characteristic (ROC) curve methods were used to compare the effect of
      both the didactic session and the viewing condition on diagnostic accuracy.
      RESULTS: There were no significant differences in performance before and after
      the didactic session and no differences between the two viewing conditions. After
      including only abnormal radiographs that demonstrated the "spine sign" (an
      apparent increased opacification of the lower vertebral bodies on the lateral
      view), the residents performed better when presented with both PA and lateral
      radiographs than when presented with the PA radiograph only (area under ROC
      curve, .8158 vs .7418, respectively; P = 0.24). CONCLUSION: In patients with left
      lower lobe pneumonia whose radiographs demonstrated the spine sign, diagnostic
      accuracy improved when the lateral chest radiograph was viewed.

PMID- 9597100
TI  - Computerized delineation and analysis of costophrenic angles in digital chest
      radiographs.
AB  - RATIONALE AND OBJECTIVES: The authors developed a computerized method for
      delineating the costophrenic angles in digital posteroanterior chest radiographs
      to derive quantitative information that allows for detection of abnormal blunting
      of the costophrenic angle. MATERIALS AND METHODS: An automated lung-segmentation
      scheme was used, and small regions of interest were placed in the approximate
      position of the costophrenic angles in 600 clinical posteroanterior chest
      radiographs to define a subimage for further analysis. The diaphragmatic aspect
      of the costophrenic angle was delineated based on column-wise contrast
      information, and the costal aspect was delineated based on row-wise gray-level
      maxima. The angle formed by the convergence of these two aspects provided the
      basis for assessing abnormality. Curve fitting was then performed on these
      segments to form a continuous costophrenic angle delineation. RESULTS: The
      computer-determined angles for 1,166 hemithoraces were compared with independent
      diagnostic assessments by a radiologist. An encouraging level of agreement was
      found between these two measurements, with the area under the receiver operating
      characteristic curve attaining a value of 0.83. CONCLUSION: This delineation
      method enhances the automated lung-segmentation scheme. Quantitative information
      obtained from the costophrenic angles can be used for automatic evaluation of the
      presence of costophrenic angle blunting, which may indicate the presence of
      pleural effusion.

PMID- 9597101
TI  - Quantification of interstitial lung abnormalities with chest radiography:
      comparison of radiographic index and fractal dimension.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate two
      physical measures used for quantifying interstitial lung abnormalities on chest
      radiographs: the normalized radiographic index (RI) and the fractal dimension
      (FD). MATERIALS AND METHODS: The RI and FD were obtained from 50 regions of
      interest (ROIs) in lungs with mild interstitial abnormalities, 50 ROIs in lungs
      with severe interstitial abnormalities, and 50 ROIs in normal lungs. The RI was
      defined as the normalized percentage area of extracted opacities in selected
      ROIs. FD was calculated with a box-counting algorithm. To extract linear
      opacities selectively, the authors processed ROIs with four-directional Laplacian
      Gaussian filtering and binarization, linear opacity judgment (LOJ), and linear
      opacity subtraction (LOS). The usefulness of the physical measures for
      quantifying interstitial lung abnormalities was evaluated with receiver operating
      characteristic analysis. RESULTS: In normal and mild abnormality groups, observer
      performance with the RI was worse with LOJ images (area under the receiver
      operating characteristic curve [Az] = .812 +/- .042) than with LOS images (Az =
      .912 +/- .028, P < .05), and performance with FD was better with LOJ images (Az =
      .867 +/- .037) than with LOS images (Az = .750 +/- .048, P < .05). In the normal
      and severe abnormality groups, performance with RI and FD was better with LOJ
      images (RI: Az = .992 +/- .007; FD: Az = .968 +/- .016) than with LOS images (RI:
      Az = .883 +/- .034, P < .001; FD: Az = .767 +/- .047, P < .0001). CONCLUSION: The
      RI is considered to reflect the sensitivity in the detection of interstitial lung
      abnormalities on chest radiographs. Conversely, the FD is considered to reflect
      specifically the linear opacities processed with LOJ.

PMID- 9597102
TI  - Acute childhood pyelonephritis: predictive value of positive sonographic findings
      in regard to later parenchymal scarring.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the importance of positive
      sonographic findings in acute childhood pyelonephritis. MATERIALS AND METHODS: A
      total of 290 children (91 boys, 199 girls, aged 4 days to 15 years [median, 394
      days]) with clinically suspected acute pyelonephritis underwent initial renal
      gray-scale ultrasound (US) and dimercaptosuccinate scintigraphic examination
      within 3 days of onset. A total of 173 patients underwent color or energy US
      examination. One hundred fifteen children with normal scintigraphic or pathologic
      findings (other than acute pyelonephritis) were excluded from further study; 170
      patients with abnormal scintigraphic findings underwent follow-up scintigraphic
      scanning 60-90 days later. RESULTS: When pathologic structures other than acute
      pyelonephritis were not considered, the diagnostic value of gray-scale US was
      poor, with a sensitivity of 45.5%, a specificity of 86.6%, a positive predictive
      value of 88.8%, and a negative predictive value of only 40.6%. In regard to
      future renal scarring, gray-scale US had a positive predictive value of 67.7%, a
      negative predictive value of 40%, and a likelihood ratio of 1.16. Abnormal
      Doppler findings helped predict future scarring with a positive predictive value
      of 85.7%, a negative predictive value of 37.2%, a very low sensitivity of 26.9%,
      a high specificity of 90.6%, and a likelihood ratio of 2.87. CONCLUSION: Positive
      US Doppler findings in children with clinically suspected acute pyelonephritis
      indicate the need for immediate treatment. A positive initial gray-scale US
      examination does not predict future renal scarring, but a positive Doppler
      examination indicates a high probability of scarring. Negative gray-scale or
      Doppler US does not exclude a diagnosis of acute pyelonephritis and it cannot
      predict an absence of future scarring.

PMID- 9597103
TI  - Digital mammography: hybrid four-channel wavelet transform for microcalcification
      segmentation.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated an algorithm for the automatic
      segmentation of microcalcification clusters (MCCs) at digital mammography. Two-
      and four-channel wavelet transforms were evaluated to determine whether
      sensitivity in the detection of MCCs can be improved and if the selective
      reconstruction of the higher-order M2 subimages allows better preservation of the
      segmented MCCs, which is required for their classification. MATERIALS AND
      METHODS: The hybrid method involved the use of a nonlinear filter for image noise
      suppression coupled with wavelet transforms for image decomposition and an
      adaptive method for selective subimage reconstruction as a basis for segmentation
      of MCCs. The two- and four-channel wavelet transforms were implemented with
      different filter bank structures (i.e., polyphase quadrature mirror filters
      [QMFs], tree structure, and lattice structure) to determine if their
      computational efficiency can be improved while retaining properties such as near
      perfect reconstruction. The hybrid wavelet transforms were applied to a common
      image database of biopsy-proved MCCs (100 images, 105-micron resolution, 12 bits
      deep; 52 cases with at least one MCC of varying subtlety [46 malignant and six
      benign cases] and eight normal cases). RESULTS: The two- and four-channel wavelet
      transforms yielded sensitivities of 93% and 94% and false-positive (PP) detection
      rates of 1.58 and 1.35 MCCs per image, respectively. The lattice structure
      provided greater than fivefold improvement in computational speed compared to the
      polyphase QMF structure, particularly for the higher order of channels (M = 4).
      CONCLUSION: The four-channel wavelet transform provided better sensitivity and FP
      detection rates and greater image detail preservation for the segmented MCCs.

PMID- 9597104
TI  - MR imaging of rabbit hip cartilage with a clinical imager and specifically
      designed surface coils.
AB  - RATIONALE AND OBJECTIVES: The authors' purpose was to develop a magnetic
      resonance (MR) imaging technique for examining the hip joint of a rabbit with a
      clinical MR imager. MATERIALS AND METHODS: Fourteen hips of 10 male New Zealand
      white rabbits were examined on a 1.5-T MR imager with a specially designed
      surface coil. Field of view was 3-8 cm, matrix was 256-512 x 192-256, section
      thickness was 0.9-2.0 mm, and spacing was 0.3-0.5 mm. The hips were sectioned and
      evaluated by means of light microscopy. Measurements of cartilage thickness from
      MR images were correlated with those from histologic specimens. RESULTS: The
      resolution obtainable with a 1.5-T imager was adequate for imaging articular
      cartilage when a debrided rabbit hip specimen was placed in the center of a 3.5
      cm single-loop coil. Rabbit hip cartilage had a trilaminar appearance on MR
      images. The coefficient of correlation between cartilage-thickness measurements
      was .81. CONCLUSION: MR imaging of rabbit hip cartilage can be performed on 1.5-T
      clinical MR imaging unit. Limitations due to the field strength can be overcome
      with efficiently designed surface coils.

PMID- 9597105
TI  - 1998 Joseph E. Whitley, MD, Award. Relationship between American College of
      Radiology in-training examination scores and American Board of Radiology written
      examination scores. Part 2. Multi-institutional study.
AB  - RATIONALE AND OBJECTIVES: The authors assessed the relationship between resident
      performance on the American College of Radiology in-training examination and
      subsequent American Board of Radiology written examination. MATERIALS AND
      METHODS: Percentile scores from the in-training examination (low score, < 20
      percentile) and written board examination (low score, < 25 percentile) were
      collected for 513 residents from 11 university-based programs over a 7-year
      period. Mean in-training examination scores were compared for the high- and low
      score written board examination groups. In-training examination scores were
      correlated with the written board examination scores. An odds ratio was
      calculated for the association between in-training examination and written board
      examination scores; this was adjusted for resident Alpha Omega Alpha (AOA)
      status, clinical training prior to radiology residency, the year the written
      board examination was taken, program size, and regional location of the program.
      RESULTS: The mean in-training examination scores were significantly higher in the
      high-score than the low-score written board examination group (P = .0001). There
      was a significant correlation between the in-training examination score and the
      written board examination score (P = .0001). The crude all-high in-training
      scores-written board scores odds ratio was 9.618, and the adjusted all-high odds
      ratio was 7.595. The final model included resident AOA status. CONCLUSION:
      Resident average in-training examination score was a strong predictor of the
      written board examination score, as noted in the earlier report. The resident
      with a low in-training examination score is at risk for poor performance on the
      written board examination.

PMID- 9597106
TI  - Applications of spiral CT in genitourinary imaging.

PMID- 9597107
TI  - Imaging of hemangiomas and vascular malformations in children.

PMID- 9597108
TI  - Neuroradiology on the Internet.

PMID- 9597109
TI  - Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of
      regional myocardial perfusion in dogs.
AB  - Hypervolaemic haemodilution makes myocardial perfusion more homogenous as
      reflected by reduced fractal dimension of regional myocardial perfusion. The
      clinically more commonly performed acute normovolaemic haemodilution, however,
      has not yet been studied in this respect. Hyperoxic ventilation with 100% oxygen
      is used in conjunction with haemodilution to compensate for low oxygen content by
      increasing physically dissolved oxygen in plasma. Since hyperoxia is known to
      cause disturbance in microcirculatory regulation we studied the effects of acute
      normovolaemic haemodilution to haematocrit (hct) 20 +/- 1% and hyperoxia on
      regional myocardial perfusion heterogeneity in 22 anaesthetized dogs using
      fractal and correlation analysis. Regional myocardial perfusion was assessed with
      radioactive microspheres. The results of the study were that heart rate, blood
      volume and arterial pressure were unchanged during haemodilution. Cardiac index
      was 3.6 +/- 0.7 L min-1 m-2 before and 4.6 +/- 0.7 L min-1 m-2 after
      haemodilution (P < 0.05). Fractal dimension (D) of regional myocardial perfusion
      was 1.17 +/- 0.10 at baseline. Neither haemodilution (D = 1.19 +/- 0.10) nor
      hyperoxia (D = 1.17 +/- 0.10) altered fractal properties of regional myocardial
      perfusion. Spatial correlation of blood flow to adjacent tissue samples before
      haemodilution was 0.58 +/- 0.15. Haemodilution and hyperoxia did not
      significantly influence spatial correlation (0.57 +/- 0.12 vs. 0.60 +/- 0.09;
      ns). We conclude that neither acute normovolaemic haemodilution nor haemodilution
      in combination with hyperoxic ventilation alter physiological myocardial
      perfusion heterogeneity.

PMID- 9597110
TI  - Quantitative evaluation of nutritional pathways for the posterior cruciate
      ligament and the lateral collateral ligament in rabbits.
AB  - The cruciate ligament of the knee receives its nutrition from a direct vascular
      supply and by permeation of nutrients from the synovial fluid. The contributions
      of these two routes as nutritional pathways are not known in detail. In this
      study, we injected [3H]methyl glucose as a tracer intravenously or directly into
      the knee of rabbits. Tracer concentrations in plasma, synovial fluid, the
      posterior cruciate ligament (PCL), and the lateral collateral ligament (LCL) were
      analysed by a pharmacokinetic compartment model. The contribution of [3H]methyl
      glucose permeation from the synovial fluid during steady state was calculated at
      44.3% in the PCL and at 39.0% in the LCL. Although these results indicated that
      more than half the nutrition for both ligaments is provided by its vascular
      supply, synovial fluid permeation is also an important transport route for small
      molecules for the PCL and the LCL, which is an extra-articular structure.

PMID- 9597111
TI  - Increase in serum vascular endothelial growth factor levels during altitude
      training.
AB  - The present study was performed to evaluate the effects of physical exercise at
      altitudes on serum vascular endothelial growth factor (VEGF) levels. Eight
      subjects underwent intensive swimming training for 21 days at 1886 m. After
      altitude training commenced, red blood cell (RBC) counts and erythropoietin
      levels increased, but both haemoglobin and haematocrit levels did not change
      significantly. The serum level of VEGF, measured by means of a highly sensitive
      chemiluminescence (ELISA), showed a transient decrease 10 days after start of the
      altitude training, thereafter increasing significantly to reach a peak level 19
      days later, rising from 23.0 +/- 5.3 to 46.0 +/- 14.6 pg mL-1 (P < 0.05 vs.
      before). On return to low altitude in Japan, the level of VEGF decreased, and 1
      month later had returned to initial levels. Endurance training at altitudes
      increases serum VEGF levels; this could be an adaptive reaction to hypoxic
      conditions. This result suggests that VEGF may provide a new physiological
      parameter for hypoxic stress imposed by high altitude training.

PMID- 9597113
TI  - Neural and non-neural activation of electrogenic secretion by 5-hydroxytryptamine
      in the rat ileum in vitro.
AB  - 5-hydroxytryptamine (5-HT) stimulates electrogenic Cl- secretion in rat ileum
      stripped of its outer smooth musculature and myenteric plexus. The myenteric
      plexus, however, is a site of 5-HT synthesis in the gut, and the plexus mediates
      electrogenic ion secretion activated by luminal enterotoxin STa and taurocholate.
      Thus, we investigated the role of the myenteric plexus in 5-HT-induced
      electrogenic secretion in vitro by measuring short-circuit current (Isc,
      microamps) with voltage-clamp apparatus as an index of electrogenic Cl-secretion
      in rat ileum which was either stripped of the myenteric plexus or was left
      intact. Serosally added 5-HT stimulated electrogenic Cl- secretion in muscle
      stripped and intact ileum in a concentration-dependent manner. Pre-treatment of
      stripped ileum with atropine (1 micron), hexamethonium (100 microns),
      tetrodotoxin (1.25 microns) and capsaicin (1 micron) for 15 min did not effect
      the maximum Isc induced by 5-HT which would implicate a direct action on the
      enterocyte. In intact ilea, however, tetrodotoxin (TTX) and capsaicin reduced
      significantly the maximum values of Isc stimulated by 5-HT, and the nitric oxide
      synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) caused a
      significant decrease in the maximum response to 5-HT. These results suggest that
      electrogenic secretion induced by 5-HT in rat ileum in vitro occurs partly by
      activation of a non-neural pathway probably involving a direct interaction with
      the enterocyte, and partly via a nitrinergic-myenteric secretory reflex activated
      by sensory afferent fibres. These data highlight the danger of characterising
      intestinal secretory activity from in vitro experiments by using muscle-stripped
      tissue only.

PMID- 9597112
TI  - Acid-induced duodenal mucosal nitric oxide output parallels bicarbonate secretion
      in the anaesthetized pig.
AB  - We recently showed the involvement of the L-arginine/nitric oxide (NO) pathway in
      acid-induced duodenal mucosal bicarbonate secretion in rats. The aim of the
      present study was to confirm this observation in pigs by direct measurements of
      NO production. Experiments were performed on 16 anaesthetized pigs of both sexes
      treated with guanethidine (6 mg kg-1, intravenously). A duodenal segment, devoid
      of pancreaticobiliary influxes, was perfused with saline and the duodenal mucosal
      bicarbonate secretion was calculated from continuous measurements of pH and PCO2.
      The perfusate contents of NO and its oxidative product nitrite were determined by
      chemiluminescence, after reduction of nitrite to NO. Luminal acidification with
      30 mM hydrochloric acid increased the output of bicarbonate as well as NO to the
      perfusate, by 195 +/- 45% and 106 +/- 10%, respectively. These responses to acid
      were markedly inhibited by adding the NO synthase inhibitor NG-monomethyl-L
      arginine (L-NMMA, 0.3 mM) to the perfusate. The inhibitory effect of L-NMMA could
      be reversed by administration of L-arginine (3 mM). The study presents
      simultaneous measurements of bicarbonate and NO outputs to a duodenal luminal
      perfusate. The results strongly support the view that the L-arginine/NO pathway
      is involved in the acid-induced duodenal mucosal bicarbonate secretory response.

PMID- 9597114
TI  - The role of antidiuretic hormone in cold-induced diuresis in the anaesthetized
      rat.
AB  - The aim of this study was to investigate whether the increased diuresis in
      consequence of hypothermia is due to a depression of the hypothalamic release of
      antidiuretic hormone (ADH). The plasma concentration of antidiuretic hormone and
      the effect of intravenous (i.v.) administration of 65 ng kg-1 desmopressin
      (selective V2-receptor agonist) were determined in the anaesthetized rat. In
      spite of a 50% (P < 0.001) decrease in glomerular filtration rate, urine flow
      increased sixfold (P < 0.01) and urine sodium excretion increased sevenfold (P <
      0.05), whereas urine osmolality decreased (P < 0.001). At the same time plasma
      antidiuretic hormone decreased from 7.5 +/- 1.1 to 3.8 +/- 0.4 pg mL-1 (P =
      0.01). After injection of desmopressin urine flow was completely restored,
      whereas urine osmolality and sodium excretion were only partially normalized.
      Since tubular conservation of water and fractional water reabsorption decreased
      during hypothermia, the diuresis must have resulted from an augmented loss of
      water. This is further supported by the fact that osmolal excretion was not
      influenced either by hypothermia or by desmopressin. It is concluded that the
      diuresis in consequence to hypothermia is due both to a decrease in the release
      of ADH and to a reduction of renal medullary hypertonicity.

PMID- 9597115
TI  - Glomerular charge selectivity for proteins larger than serum albumin as revealed
      by lactate dehydrogenase isoforms.
AB  - It is well known that macromolecules like albumin are markedly restricted in
      their passage across the glomerular capillary wall. However, the relative
      importance of solute size, charge and shape is currently debated since much of
      the previous work is based on dextran in neutral or charge-modified forms. These
      polymers have certain drawbacks that make them less suitable for analysis of
      capillary permeability and the notion of a glomerular charge barrier has
      therefore been questioned. Moreover, macromolecules larger than albumin (mol. wt.
      69,000) have been suggested to pass through nonselective 'shunt' pathways. In
      order to study glomerular permeability, isolated rat kidneys were perfused with
      albumin solutions containing trace amounts of two differently radiolabelled
      isoenzymes of lactate dehydrogenase (LDH) at low temperature to inhibit tubular
      function. The isoenzymes have similar size (mol. wt. 140,000) and shape but
      differ in charge, one carrying a negative net surface charge (LDH1, -19) and the
      other being slightly cationic (LDH5, +2). The urine and perfusate samples were
      subjected to high pressure liquid chromatography (HPLC) gel-filtration to allow
      for measurements of intact LDH. The fractional clearance was 0.11% +/- 0.04% for
      the anionic LDH1 and 0.56% +/- 0.07% for LDH5, whereas that for albumin was 0.21%
      +/- 0.03% at a glomerular filtration rate of 0.11 +/- 0.01 mL min-1 g-1 kidney
      wet weight. The results were analysed using a homogenously charged membrane model
      and are compatible with a charge density of 35 mEq L-1, with 95% confidence
      interval of 26-41 mEq L-1. These findings suggest a significant glomerular charge
      selectivity for proteins substantially larger than albumin. The charge density
      is, however, far less than estimated from dextran studies.

PMID- 9597116
TI  - Different renal effects of two inhibitors of catechol-O-methylation in the rat:
      entacapone and CGP 28014.
AB  - Dopamine is a natriuretic hormone that is abundantly synthesized in the kidney
      and is involved in sodium homeostasis. It is metabolized by monoamine oxidase
      (MAO) and catechol-O-methyl transferase (COMT) to form 3-methoxytyramine and
      dihydroxyphenylacetic acid (DOPAC) and finally homovanillic acid (HVA). In order
      to investigate whether dopamine metabolism is involved in renal sodium
      regulation, we tested the renal effects of the nitrocatechol entacapone (COMT
      inhibitor), in comparison with those of the pyridine derivative CGP 28014, in the
      anaesthetized rat. Entacapone injection resulted in a more than 5-fold increase
      in sodium excretion, while the renal excretion of dopamine only transiently
      increased by 20%. DOPAC excretion showed a more than 2-fold increase which
      persisted throughout the study. Pretreatment with the selective dopamine DA1
      receptor antagonist SCH23390 reduced the entacapone-induced natriuretic response
      by 69%. Glomerular filtration rate (GFR) and mean arterial blood pressure (MAP)
      remained unchanged. Injection of CGP 28014 did not produce a natriuretic
      response; nevertheless, both dopamine and DOPAC excretion increased by 78% and
      more than 2-fold, respectively. GFR and MAP remained unchanged. In conclusion,
      COMT inhibition using entacapone results in a mainly DA1 receptor mediated
      natriuresis involving inhibition of tubular transport processes, supporting a
      role for dopamine metabolism in sodium homeostasis. Although CGP 28014 increases
      the renal excretion of both dopamine and DOPAC it does not affect renal sodium
      handling indicating a different mechanism of action.

PMID- 9597118
TI  - Near-infrared spectrophotometry determined brain oxygenation during fainting.
AB  - During orthostatic hypotension we evaluated whether presyncopal symptoms relate
      to a reduced brain oxygenation. Nine subjects performed 50 degrees head-up tilt
      for 1 h and eight subjects were followed during 2 h of supine rest and during 1 h
      of 10 degrees head-down tilt. Cerebral perfusion was assessed by transcranial
      Doppler determined middle cerebral artery blood velocity (MCA vmean), while brain
      blood oxygenation was assessed by near-infrared spectrophotometry determined
      concentration changes for oxygenated (delta HbO2) and deoxygenated haemoglobin
      and brain cell oxygenation by the oxidized cytochrome c concentration (delta
      CytO2). During head-up tilt, six volunteers developed presyncopal symptoms and
      mean arterial pressure (88 (78-103) to 68 (57-79) mmHg; median and range), heart
      rate (96 (72-111) to 65 (50-107) beats min-1), MCA vmean (59 (51-82) to 41 (29
      56) cm s-1), delta HbO2 (by -5.3 (-3.0 to -14.8) mumol l-1) and delta CytO2 were
      reduced (by -0.2 (-0.1 to -0.4) mumol l-1; P < 0.05). During tilt down the
      cardiovascular variables recovered immediately and delta HbO2 increased to 2.2 (
      0.9-12.0) mmol L-1 above the resting value and also delta CytO2 recovered. In the
      nonsyncopal head-up tilted subjects as in the controls, blood pressure, heart
      rate, MCA vmean and brain oxygenation indices remained stable. The results
      suggest that during orthostasis, presyncopal symptoms relate not only to cerebral
      hypoperfusion but also to reduced brain oxygenation.

PMID- 9597117
TI  - In vivo 31P NMR OSIRIS of bioenergetic changes in rabbit kidneys during and after
      ischaemia: effect of pretreatment with an indeno-indole compound.
AB  - Changes in energy phosphates of rabbit kidneys subjected to ischaemia-reperfusion
      have been measured in vivo with volume selective 31P NMR spectroscopy. The
      effects of pretreatment with a new lipid peroxidation inhibitor (indeno-indol
      derivate--code name H290/51) on the bioenergetic changes were analysed. The left
      kidney was moved to a subcutaneous pocket to facilitate exact positioning over
      the surface coil. A 1H NMR image was acquired and a 3.5-mL cube selected for 31P
      NMR spectra. 31P NMR spectra were recorded before occlusion of the left renal
      artery, during 1 h of ischaemia and 2 hours of reperfusion. Ischaemia induced
      drastic changes in the levels of inorganic phosphates and ATP as well as
      intracellular acidosis. A normalization was observed during reperfusion. Two
      hours after reperfusion significantly higher values for beta-ATP/Pi and
      intracellular pH were recorded in the animals pretreated with H290/51. The
      present technique allows quantitative analyses of changes in kidney bioenergetics
      in vivo during different experimental conditions. The importance of ischaemia
      reperfusion induced lipid peroxidation for mitochondrial function is emphasized.

PMID- 9597119
TI  - Regional brain serotonin receptor changes in portacaval shunted rats.
AB  - The pathogenesis of hepatic encephalopathy is unknown, but metabolic
      perturbations, including hyperammonaemia and increased brain turnover of
      serotonin (5-HT), have been identified. Possible alterations of 5-HT receptors in
      the brain have been rudimentarily studied. We therefore investigated the 5-HT1A,
      5-HT1B and 5-HT2A receptor density in 18-22 different regions in the brain of
      portacaval shunted rats by means of radioligand binding with autoradiographical
      evaluation. The results revealed a decreased 5-HT1A receptor binding in seven
      serotonergic projection areas of the brain, and an increase in the nucleus
      accumbens, hypothalamus and subiculum. No changes in the raphe nuclei were
      observed. An increased 5-HT1B receptor binding was seen in five brain regions:
      basal ganglia, olfactorial regions, hippocampus, mid brain and thalamus. However,
      decreased binding was seen in three regions of cortical areas and hippocampus.
      The 5-HT2A receptor binding site density was essentially unaltered. These
      findings suggest that perturbations in the central serotonergic neurotransmission
      may play a functional role in chronic hepatic encephalopathy.

PMID- 9597120
TI  - Effects of physical activity and acupuncture on calcitonin gene-related peptide
      immunoreactivity in different parts of the rat brain and in cerebrospinal fluid,
      serum and urine.
AB  - Calcitonin gene-related peptide (CGRP) is a very potent vasodilator in the
      nervous system, and may be involved in hot flushes experienced by most women
      around menopause. Flushing post-menopausal women had higher urinary excretion of
      CGRP before than after successful treatment of their flushes with acupuncture.
      The prevalence of vasomotor symptoms is lower in physically active women. In a
      rat model we therefore intended to assess whether acupuncture and exercise
      affected CGRP concentrations in different parts of the brain and peripherally.
      The aim of the study was to elucidate the short- and long-term effects of
      exercise and acupuncture on CGRP concentrations in the nervous system of normal
      adult rats. In a rat model, we examined the effects of single interventions and
      long-term treatment with physical exercise and manual or electro-acupuncture on
      CGRP concentrations in urine, cerebrospinal fluid and serum and different parts
      of the brain. In all compartments studied, but significantly only in the
      cerebrospinal fluid, CGRP increased after a single session of physical exercise
      or electro-acupuncture. Manual acupuncture did not change CGRP concentrations in
      any compartment. Rats had the highest concentrations of CGRP in the pituitary and
      hypothalamus but the concentrations did not differ significantly between control
      rats and those subjected to long-term treatment with manual or electro
      acupuncture or running rats. Rats treated with electro-acupuncture had twice the
      CGRP concentration in the frontal cortex compared to control rats, albeit the
      difference did not reach statistical significance. Evidently manual and electro
      acupuncture have different effects, whereas electro-acupuncture and physical
      exercise have more similar effects on CGRP production and/or release. To
      elucidate the role of CGRP in vasomotor symptoms, further studies with older
      flushing rats should be performed.

PMID- 9597121
TI  - Functional characterisation of receptors for cysteinyl leukotrienes in smooth
      muscle.
AB  - The cysteinyl leukotrienes (leukotriene C4, D4 and E4) have potent biological
      actions which significantly contribute to the airway obstruction in asthma.
      Several of these effects are blocked by drugs known as CysLT1-receptor
      antagonists. However, there are actions of leukotrienes which are not sensitive
      to these antagonists, suggesting the presence of additional receptor subtypes. It
      was the aim of this Thesis to extend the knowledge about receptors for cysteinyl
      leukotrienes. Three different isolated smooth muscle preparations kept in organ
      baths under non-flow conditions were characterised with respect to responsiveness
      to cysteinyl leukotrienes and sensitivity to purported CysLT1-receptor
      antagonists. In addition, the study involved evaluation of a leukotriene E4
      analogue, BAY u9773, suggested to inhibit responses which cannot be blocked by
      CysLT1-receptor antagonists. These responses have provisionally been considered
      to be mediated by CysLT2-receptors. In the guinea pig ileum, BAY u9773 but not
      the selective CysLT1 receptor antagonist ICI 198,615 inhibited the contractile
      response to leukotriene C4 in a fashion suggesting competitive antagonism. In
      sheep trachealis muscle, BAY u9773 antagonised contractions induced by
      leukotriene C4 and leukotriene D4 in a similar manner, whereas ICI 198,615 did
      not. The observations support that leukotriene C4 in guinea pig ileum, and
      leukotriene C4 as well as leukotriene D4 in sheep trachealis muscle, mediated
      contractions via activation of CysLT2-receptors. In guinea pig lung parenchyma,
      the effects of BAY u9773 and conventional cysteinyl leukotriene receptor
      antagonists (ICI 198,615, FPL 55,712) were more complex. First, BAY u9773 evoked
      a contraction, which could be inhibited by antagonists of CysLT1- and TP
      receptors. This suggested that BAY u9773 acted as an agonist at these two
      receptors. Second, pretreatment with BAY u9773 inhibited a distinct but
      relatively small component of the contractile response to leukotriene C4 and D4.
      The effects of BAY u9773 and ICI 198,615 were similar in guinea pig lung
      parenchyma. The findings suggest that the receptor mediating the major part of
      the contractile response to exogenous cysteinyl leukotrienes in guinea pig lung
      parenchyma was different from the currently defined CysLT2-receptor. Furthermore,
      the data suggested that BAY u9773 was a partial agonist at cysteinyl leukotriene
      receptors, which presumably contributed to its profile of activity as a combined
      CysLT1- and CysLT2-receptor antagonist. In addition to contracting guinea pig
      lung parenchyma, leukotriene C4 and lipoxin A4 also evoked release of thromboxane
      A2. This release was sensitive to CysLT1-receptor antagonists and contributed to
      part of the contractile response. Finally, the investigations included a
      characterisation of the role of leukotrienes in antigen-induced contractions of
      lung parenchyma from actively sensitised guinea pigs. Combination of
      antihistamines with CysLT1-receptor antagonists or inhibitors of leukotriene
      biosynthesis blocked the major component of the antigen-induced contraction. The
      findings are similar to those observed in isolated human bronchi and support that
      this model may be used to investigate mediator mechanisms of relevance to asthma.

PMID- 9597122
TI  - Eureka! And other pleasures.
AB  - At first one is very pleased at being invited to write a Prefatory Chapter, but
      as the delivery deadline draws closer one begins to think, "Oh my God! What on
      earth can I say that all but family members and few close friends will not find a
      great bore?" One solution is to write a scientific essay, but I concluded that
      that was a cop-out. I decided that perhaps the best tack to follow was to try to
      convey to the reader the personal characteristics I bring to my science and to
      other aspects of my professional career. The writing of this chapter has
      certainly convinced me that my particular background influenced what problems I
      chose to work on and how I approached their solution, but I hope that my results
      have a more ecumenical significance. There's been much written recently about how
      one's cultural background affects one's science, but I think that thesis can also
      be exaggerated. Science is a method of inquiry that by using certain guidelines
      permits rational individuals to observe Nature in a way that their findings will
      agree and have permanence. We shouldn't be diffident about defending that claim
      of objectivity.

PMID- 9597123
TI  - Interleukin-1 receptor antagonist: role in biology.
AB  - The interleukin-1 receptor antagonist (IL-1Ra) is a member of the IL-1 family
      that binds to IL-1 receptors but does not induce any intracellular response. Two
      structural variants of IL-1Ra have previously been described: a 17-kDa form that
      is secreted from monocytes, macrophages, neutrophils, and other cells (sIL-1Ra)
      and an 18-kDa form that remains in the cytoplasm of keratinocytes and other
      epithelial cells, monocytes, and fibroblasts (icIL-1Ra). An additional 16-kDa
      intracellular isoform of IL-1Ra has recently been described in neutrophils,
      monocytes, and hepatic cells. Both of the major isoforms of IL-1Ra are
      transcribed from the same gene through the use of alternative first exons. The
      two promoters regulating transcription of the secreted and intracellular forms
      have been cloned, and some of the functional cis-acting DNA regions have been
      characterized. The production of IL-1Ra is stimulated by many substances
      including adherent IgG, other cytokines, and bacterial or viral components. The
      tissue distribution of IL-1Ra in mice indicates that sIL-1Ra is found
      predominantly in peripheral blood cells, lungs, spleen, and liver, while icIL-1Ra
      is found in large amounts in skin. Studies in transgenic and knockout mice
      indicate that IL-1Ra is important in host defense against endotoxin-induced
      injury. IL-1Ra is produced by hepatic cells with the characteristics of an acute
      phase protein. Endogenous IL-1Ra is produced in numerous experimental animal
      models of disease as well as in human autoimmune and chronic inflammatory
      diseases. The use of neutralizing anti-IL-1Ra antibodies has demonstrated that
      endogenous IL-1Ra is an important natural antiinflammatory protein in arthritis,
      colitis, and granulomatous pulmonary disease. Treatment of human diseases with
      recombinant human IL-1Ra showed an absence of benefit in sepsis syndrome.
      However, patients with rheumatoid arthritis treated with IL-1Ra for six months
      exhibited improvements in clinical parameters and in radiographic evidence of
      joint damage.

PMID- 9597124
TI  - Pathways and strategies for developing a malaria blood-stage vaccine.
AB  - In the past 10 years, our knowledge of the malaria parasite has increased
      enormously: identification and analysis of parasite antigens, demonstration of
      protection of monkeys and mice following immunization with these antigens, and
      better understanding of the mechanisms of immunity to malaria and the
      pathogenesis of disease in malaria. Powerful new adjuvants have been developed,
      some of which--it is hoped--will be suitable for human use. Recently, a
      successful human trial of a vaccine aimed at sporozoites (the stage inoculated by
      mosquitoes) was completed. However, it is the red blood cell stage of the
      parasite that causes disease, and it is against this stage--in which the parasite
      grows at an exponential rate--that it has proven very difficult to induce a
      protective immune response by vaccination. This review focuses on recent exciting
      developments toward a blood-stage vaccine. We analyze the major obstacles to
      vaccine development and outline a strategy involving public- and industry-funded
      research that should result in development of a vaccine.

PMID- 9597125
TI  - CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in
      the immune system.
AB  - CD81 (TAPA-1) is a widely expressed cell-surface protein involved in an
      astonishing variety of biologic responses. It has been cloned independently
      several times for different functional effects and is reported to influence
      adhesion, morphology, activation, proliferation, and differentiation of B, T, and
      other cells. On B cells CD81 is part of a complex with CD21, CD19, and Leu13.
      This complex reduces the threshold for B cell activation via the B cell receptor
      by bridging Ag specific recognition and CD21-mediated complement recognition.
      Similarly on T cells CD81 associates with CD4 and CD8 and provides a
      costimulatory signal with CD3. In fetal thymic organ culture, mAb to CD81 block
      maturation of CD4-CD8- thymocytes, and expression of CD81 on CHO cells endows
      those cells with the ability to support T cell maturation. However, CD81
      deficient mice express normal numbers and subsets of T cells. These mice do
      exhibit diminished antibody responses to protein antigens. CD81 is also
      physically and functionally associated with several integrins. Anti-CD81 can
      activate integrin alpha 4 beta 1 (VLA-4) on B cells, facilitating their adhesion
      to tonsilar interfollicular stroma. Similarly, anti-CD81 can activate alpha L
      beta 2 (LFA-1) on human thymocytes. CD81 can also affect cognate B-T cell
      interactions because anti-CD81 increases IL-4 synthesis by T cells responding to
      antigen presented by B cells but not by monocytes. The tetraspanin superfamily
      (or TM4SF) includes CD81, CD9, CD37, CD53, CD63, CD82, CD151, and an increasing
      number of additional proteins. Like CD81, several tetraspanins are involved in
      cell adhesion, motility, and metastasis, as well as cell activation and signal
      transduction.

PMID- 9597126
TI  - CD40 and CD154 in cell-mediated immunity.
AB  - CD40-CD154-mediated contact-dependent signals between B and T cells are required
      for the generation of thymus dependent (TD) humoral immune responses. CD40-CD154
      interactions are however also important in many other cell systems. CD40 is
      expressed by a large variety of cell types other than B cells, and these include
      dendritic cells, follicular dendritic cells, monocytes, macrophages, mast cells,
      fibroblasts, and endothelial cells. CD40- and CD154-knockout mice and antibodies
      to CD40 and CD154 have helped to elucidate the role of the CD40-CD154 system in
      immune responses. Recently published studies indicate that CD40-CD154
      interactions can influence T cell priming and T cell-mediated effector functions;
      they can also upregulate costimulatory molecules and activate macrophages, NK
      cells, and endothelia as well as participate in organ-specific autoimmune
      disease, graft rejection, and even atherosclerosis. This review focuses on the
      role of the CD40-CD154 system in the regulation of many newly discovered
      functions important in inflammation and cell-mediated immunity.

PMID- 9597127
TI  - Regulation of immune responses by TGF-beta.
AB  - The transforming growth factor beta (TGF-beta) family of proteins are a set of
      pleiotropic secreted signaling molecules with unique and potent immunoregulatory
      properties. TGF-beta 1 is produced by every leukocyte lineage, including
      lymphocytes, macrophages, and dendritic cells, and its expression serves in both
      autocrine and paracrine modes to control the differentiation, proliferation, and
      state of activation of these immune cells. TGF-beta can modulate expression of
      adhesion molecules, provide a chemotactic gradient for leukocytes and other cells
      participating in an inflammatory response, and inhibit them once they have become
      activated. Increased production and activation of latent TGF-beta have been
      linked to immune defects associated with malignancy and autoimmune disorders, to
      susceptibility to opportunistic infection, and to the fibrotic complications
      associated with chronic inflammatory conditions. In addition to these roles in
      disease pathogenesis, TGF-beta is now established as a principal mediator of oral
      tolerance and can be recognized as the sine qua non of a unique subset of
      effector cells that are induced in this process. The accumulated knowledge gained
      through extensive in vitro functional analyses and from in vivo animal models,
      including newly established TGF-beta gene knockout and transgenic mice, supports
      the concept that clinical therapies based on modulation of this cytokine
      represent an important new approach to the treatment of disorders of immune
      function.

PMID- 9597128
TI  - Transcriptional regulation during B cell development.
AB  - Information is increasingly available concerning the molecular events that occur
      during primary and antigen-dependent stages of B cell development. In this review
      the roles of transcription factors and coactivators are discussed with respect to
      changes in expression patterns of various genes during B cell development.
      Transcriptional regulation is also discussed in the context of developmentally
      regulated immunoglobulin gene V(D)J recombination, somatic hypermutation, and
      isotype switch recombination.

PMID- 9597129
TI  - T cell memory.
AB  - Immunological memory can be defined as the faster and stronger response of an
      animal that follows reexposure to the same antigen. By this definition, it is an
      operational property of the whole animal or the immune system. Memory cells
      express a different pattern of cell surface markers, and they respond in several
      ways that are functionally different from those of naive cells. Murine memory
      cells are CD44 high and low in the expression of activation markers such as CD25
      (IL-2R), whereas human memory cells are CD45RA-, CD45RO+. In contrast to naive
      cells, memory cells secrete a full range of T cell cytokines and can be polarized
      to secrete particular restricted patterns of secretion for both CD4 and CD8 T
      cells. The requirements for the activation of memory cells for proliferation and
      cytokine production are not quite as strict as those of naive cells, but
      costimulation in the broad sense is required for optimum responses and for
      responses to suboptimum antigen concentrations. It would appear that memory cells
      can persist in the absence of antigenic stimulation and persist as nondividing
      cells. Reencounter with the same antigen can expand the population to a new,
      stable, higher level and generate a separate population of CD44 high effectors
      that may be required for protection, while competition from other antigens can
      drive it down to a lower stable level. It is unclear how or where memory cells
      arise, but once generated they have different pathways of recirculation and
      homing.

PMID- 9597130
TI  - NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune
      responses.
AB  - The transcription factor NF-kappa B, more than a decade after its discovery,
      remains an exciting and active area of study. The involvement of NF-kappa B in
      the expression of numerous cytokines and adhesion molecules has supported its
      role as an evolutionarily conserved coordinating element in the organism's
      response to situations of infection, stress, and injury. Recently, significant
      advances have been made in elucidating the details of the pathways through which
      signals are transmitted to the NF-kappa B:I kappa B complex in the cytosol. The
      field now awaits the discovery and characterization of the kinase responsible for
      the inducible phosphorylation of I kappa B proteins. Another exciting development
      has been the demonstration that in certain situations NF-kappa B acts as an anti
      apoptotic protein; therefore, elucidation of the mechanism by which NF-kappa B
      protects against cell death is an important goal. Finally, the generation of
      knockouts of members of the NF-kappa B/I kappa B family has allowed the study of
      the roles of these proteins in normal development and physiology. In this review,
      we discuss some of these recent findings and their implications for the study of
      NF-kappa B.

PMID- 9597131
TI  - Genetic susceptibility to systemic lupus erythematosus.
AB  - Considerable evidence suggests that the development of systemic lupus
      erythematosus (SLE) has a strong genetic basis. Recent studies have emphasized
      that this disease, like other autoimmune diseases, is a complex genetic trait
      with contributions from major histocompatibility complex (MHC) genes and multiple
      non-MHC genes. Etiologic genes in these disorders determine susceptibility, and
      no particular gene is necessary or sufficient for disease expression. Studies of
      murine models of lupus have provided important insight into the
      immunopathogenesis of IgG autoantibody production and lupus nephritis, and
      genetic analyses of these mice overcome certain obstacles encountered when
      studying patients. Genome-wide linkage studies of different crosses have mapped
      the position of at least 12 non-MHC disease-susceptibility loci in the New
      Zealand hybrid model of lupus. Although the identity of the actual genes is
      currently unknown, recent studies have begun to characterize how these genetic
      contributions may function in the autoimmune process, especially in terms of
      their role in autoantibody production. Studies of MHC gene contributions in New
      Zealand mice have shown that heterozygosity for particular haplotypes greatly
      increases pathogenic autoantibody production and the incidence of severe
      nephritis. The mechanism for this effect appears to be genetically complex.
      Studies in human SLE have mostly focused on the association of disease with
      alleles of immunologically relevant genes, especially in the MHC. Associations
      with various complement component deficiencies and an allele of a particular Fc
      gamma receptor gene (FCGR2A) also have been described. In a diversion from
      previous association studies, a recent directed linkage analysis of sibpairs with
      SLE was based on mapping studies in murine lupus and may be an important step
      toward identifying a new disease-susceptibility gene in patients. Since the genes
      that predispose to autoimmunity are probably related to key events in
      pathogenesis, their identification in patients and murine models will almost
      certainly provide important insight into the breakdown of immunological self
      tolerance and the cause of autoimmune disease.

PMID- 9597132
TI  - Jaks and STATs: biological implications.
AB  - Cytokines and interferons are molecules that play central roles in the regulation
      of a wide array of cellular functions in the lympho-hematopoietic system. These
      factors stimulate proliferation, differentiation, and survival signals, as well
      as specialized functions in host resistance to pathogens. Although cytokines are
      known to activate multiple signaling pathways that together mediate these
      important functions, one of these pathways, the Jak-STAT pathway, is the focus of
      this chapter. This pathway is triggered by both cytokines and interferons, and it
      very rapidly allows the transduction of an extracellular signal into the nucleus.
      The pathway uses a novel mechanism in which cytosolic latent transcription
      factors, known as signal transducers and activators of transcription (STATs), are
      tyrosine phosphorylated by Janus family tyrosine kinases (Jaks), allowing STAT
      protein dimerization and nuclear translocation. STATs then can modulate the
      expression of target genes. The basic biology of this system, including the range
      of known Jaks and STATs, is discussed, as are the defects in animals and humans
      lacking some of these signaling molecules.

PMID- 9597133
TI  - Mechanisms of MHC class I--restricted antigen processing.
AB  - Classical class I molecules assemble in the endoplasmic reticulum (ER) with
      peptides mostly generated from cytosolic proteins by the proteasome. The activity
      of the proteasome can be modulated by a variety of accessory protein complexes. A
      subset of the proteasome beta-subunits (LMP2, LMP7, and MECL-1) and one of the
      accessory complexes, PA28, are upregulated by gamma-interferon and affect the
      generation of peptides to promote more efficient antigen recognition. The
      peptides are translocated into the ER by the transporter associated with antigen
      processing (TAP). A transient complex containing a class I heavy chain-beta 2
      microglobulin (beta 2 m) dimer is assembled onto the TAP molecule by successive
      interactions with the ER chaperones calnexin and calreticulin and a specialized
      molecule, tapasin. Peptide binding releases the class I-beta 2 m dimer for
      transport to the cell surface, while lack of binding results in proteasome
      mediated degradation. The products of certain nonclassical MHC-linked class I
      genes bind peptides in a similar way. A homologous set of beta 2 m-associated
      membrane glycoproteins, the CD1 molecules, appears to bind lipid-based ligands
      within the endocytic pathway.

PMID- 9597134
TI  - NK cell receptors.
AB  - NK cells are regulated by opposing signals from receptors that activate and
      inhibit effector function. While positive stimulation may be initiated by an
      array of costimulatory receptors, specificity is provided by inhibitory signals
      transduced by receptors for MHC class I. Three distinct receptor families, Ly49,
      CD94/NKG2, and KIR, are involved in NK cell recognition of polymorphic MHC class
      I molecules. A common pathway of inhibitory signaling is provided by ITIM
      sequences in the cytoplasmic domains of these otherwise structurally diverse
      receptors. Upon ligand binding and activation, the inhibitory NK cell receptors
      become tyrosine phosphorylated and recruit tyrosine phosphatases, SHP-1 and
      possibly SHP-2, resulting in inhibition of NK cell-mediated cytotoxicity and
      cytokine expression. Recent studies suggest these inhibitory NK cell receptors
      are members of a larger superfamily containing ITIM sequences, the inhibitory
      receptor superfamily (IRS).

PMID- 9597135
TI  - BCL-2 family: regulators of cell death.
AB  - An expanding family of BCL-2 related proteins share homology, clustered within
      four conserved regions, namely BCL-2 homology (BH1-4) domains, which control the
      ability of these proteins to dimerize and function as regulators of apoptosis.
      Moreover, BCL-XL, BCL-2, and BAX can form ion-conductive pores in artificial
      membranes. The BCL-2 family, comprised of both pro-apoptotic and anti-apoptotic
      members, acts as a checkpoint upstream of CASPASES and mitochondrial dysfunction.
      BID and BAD possess the minimal death domain BH3, and the phosphorylation of BAD
      connects proximal survival signals to the BCL-2 family. BCL-2 and BCL-XL display
      a reciprocal pattern of expression during lymphocyte development. Gain- and loss
      of-function models revealed stage-specific roles for BCL-2 and BCL-XL. BCL-2 can
      rescue maturation at several points of lymphocyte development. The BCL-2 family
      also reveals evidence for a cell-autonomous coordination between the opposing
      pathways of proliferation and cell death.

PMID- 9597136
TI  - Divergent roles for Fc receptors and complement in vivo.
AB  - Recent results obtained in mice deficient in either FcRs or complement have
      revealed distinct functions for these two classes of molecules. While each is
      capable of interacting with antibodies or immune complexes, the two systems
      mediate distinct biological effector responses. Complement-deficient mice are
      unable to mediate innate immune responses to several bacterial pathogens and
      bacterial toxins, yet respond normally to the presence of cytotoxic antibodies
      and pathogenic immune complexes. In contrast, FcR-deficient mice display no
      defects in innate immunity or susceptibility to a variety of pathogens, yet they
      are unable to mediate inflammatory responses to cytotoxic IgG antibodies or IgG
      immune complexes, despite the presence of a normal complement system. These
      results lead to the surprising conclusion that these two systems have evolved
      distinct functions in host immunity, with complement and its receptors mediating
      the interaction of natural antibodies (IgM) with pathogens to effect protection,
      while FcRs couple the interaction of IgG antibodies to effector cells to trigger
      inflammatory sequelae. These results necessitate a fundamental revision of the
      role of these antibody-binding systems in the immune response.

PMID- 9597137
TI  - Xenogeneic transplantation.
AB  - This review summarizes the clinical history and rationale for
      xenotransplantation; recent progress in understanding the physiologic,
      immunologic, and infectious obstacles to the procedure's success; and some of the
      strategies being pursued to overcome these obstacles. The problems of
      xenotransplantation are complex, and a combination of approaches is required. The
      earliest and most striking immunologic obstacle, that of hyperacute rejection,
      appears to be the closest to being solved. This phenomenon depends on the binding
      of natural antibody to the vascular endothelium, fixation of complement by that
      antibody, and finally, activation of the endothelium and initiation of
      coagulation. Therefore, these three pathways have been targeted as sites for
      intervention in the process. The mechanisms responsible for the next immunologic
      barrier, that of delayed xenograft/acute vascular rejection, remain to be fully
      elucidated. They probably also involve multiple pathways, including antibody
      and/or immune cell binding and endothelial cell activation. The final immunologic
      barrier, that of the cellular immune response, involves mechanisms that are
      similar to those involved in allograft rejection. However, the strength of the
      cellular immune response to xenografts is so great that it is unlikely to be
      controlled by the types of nonspecific immunosuppression used routinely to
      prevent allograft rejection. For this reason, it may be essential to induce
      specific immunologic unresponsiveness to at least some of the most antigenic
      xenogeneic molecules.

PMID- 9597138
TI  - The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease.
AB  - One of the characteristic features of Hodgkin's disease (HD) is the presence of a
      small population of often bizarre-looking large mono- or multinucleated Hodgkin
      and Reed-Sternberg (HRS) cells within the affected tissue. Recent cytogenetic
      investigations, studies of Epstein-Barr virus (EBV) genomes present in HRS cells,
      and analyses of Ig gene rearrangements amplified from single, micromanipulated
      HRS cells show that these cells largely represent clonal populations. The finding
      of Ig gene rearrangements in HRS cells in most cases of HD identifies B cells as
      the precursors of HRS cells in most if not all cases. Furthermore, the presence
      and pattern of somatic mutations within the rearranged Ig genes show that HRS
      cells in classical (i.e. nodular sclerosis, mixed cellularity, and lymphocyte
      depletion HD) as well as lymphocyte predominant (LP) HD originate from germinal
      center (GC) B cells. Ongoing somatic mutation and evidence for selection link HRS
      cells from LP HD to a mutating, antigen-selected GC B cell. In classical HD, the
      finding of "crippling" mutations and lack of stringent selection for antigen
      receptor expression suggests that in this case HRS cells are derived from a
      compartment of GC B cells that were destined to die but escaped apoptosis by some
      transforming event. One candidate for the latter is EBV infection.

PMID- 9597139
TI  - The interleukin-12/interleukin-12-receptor system: role in normal and pathologic
      immune responses.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine that plays a central role in
      promoting type 1 T helper cell (Th1) responses and, hence, cell-mediated
      immunity. Its activities are mediated through a high-affinity receptor composed
      of two subunits, designated beta 1 and beta 2. Of these two subunits, beta 2 is
      more restricted in its distribution, and regulation of its expression is likely a
      central mechanism by which IL-12 responsiveness is controlled. Studies with
      neutralizing anti-IL-12 antibodies and IL-12-deficient mice have suggested that
      endogenous IL-12 plays an important role in the normal host defense against
      infection by a variety of intracellular pathogens. However, IL-12 appears also to
      play a central role in the genesis of some forms of immunopathology. Inhibition
      of IL-12 synthesis or activity may be beneficial in diseases associated with
      pathologic Th1 responses, such as multiple sclerosis or Crohn's disease. On the
      other hand, administration of recombinant IL-12 may have utility in the treatment
      of diseases associated with pathologic Th2 responses such as allergic disorders
      and asthma.

PMID- 9597140
TI  - Ligand recognition by alpha beta T cell receptors.
AB  - While still incomplete, the first data concerning the biochemistry of T cell
      receptor-ligand interactions in cell-free systems seem to have considerable
      predictive value regarding whether a T cell response is strong or weak or
      suppressive. This data will help considerably in elucidating the mechanisms
      behind T cell responsiveness. Also of great interest are the first structures of
      T cell receptor molecules and, particularly, TCR-ligand complexes. These appear
      to confirm earlier suggestions of a fixed orientation for TCR engagement with
      peptide/MHC and should form the basis for understanding higher oligomers,
      evidence for which has also just emerged. We conclude with an analysis of the
      highly diverse CDR3 loops found in all antigen receptor molecules and suggest
      that such regions form the core of both TCR and antibody specificity.

PMID- 9597141
TI  - The role of complement and complement receptors in induction and regulation of
      immunity.
AB  - Covalent attachment of activated complement C3 (C3d) to antigen links innate and
      adaptive immunity by targeting antigen to follicular dendritic cells (FDC) and B
      cells via specific receptors CD21 and CD35. Recent characterization of knockout
      mice deficient in complement components C3, C4, or the receptors CD21 and CD35 as
      well as biochemical studies of the CD21/CD19/Tapa-1 coreceptor on B cells have
      helped to elucidate the mechanism of complement regulation of both B-1 and B-2
      lymphocytes. Interestingly, natural antibody of the adaptive immune system
      provides a major recognition role in activation of the complement system, which
      in turn enhances activation of antigen-specific B cells. Enhancement of the
      primary and secondary immune response to T-dependent antigens is mediated by
      coligation of the coreceptor and the B cell antigen receptor, which dramatically
      increases follicular retention and B cell survival within the germinal center.
      Most recent evidence suggests that complement also regulates elimination of self
      reactive B cells, as breeding of mice that are deficient in C4 or CD21/CD35 with
      the lupus-prone strain of lpr mice demonstrates an exacerbation of disease due to
      an increase in autoantibodies.

PMID- 9597142
TI  - Dimerization as a regulatory mechanism in signal transduction.
AB  - Dynamic protein-protein interactions are a key component of biological regulatory
      networks. Dimerization events--physical interactions between related proteins-
      represent an important subset of protein-protein interactions and are frequently
      employed in transducing signals from the cell surface to the nucleus.
      Importantly, dimerization between different members of a protein family can
      generate considerable functional diversity when different protein combinations
      have distinct regulatory properties. A survey of processes known to be controlled
      by dimerization illustrates the diverse physical and biological outcomes achieved
      through this regulatory mechanism. These include: facilitated proximity and
      orientation; differential regulation by heterodimerization; generation of
      temporal and spatial boundaries; enhancement of specificity; and regulated
      monomer-to-dimer transitions. Elucidation of these mechanisms has led to the
      design of new approaches to study and to manipulate signal transduction pathways.

PMID- 9597143
TI  - The immunogenetics of human infectious diseases.
AB  - Twin and adoptee studies have indicated that host genetic factors are major
      determinants of susceptibility to infectious disease in humans. Twin studies have
      also found high heritabilities for many humoral and cellular immune responses to
      pathogen antigens, with most of the genetic component mapping outside of the
      major histocompatibility complex. Candidate gene studies have implicated several
      immunogenetic polymorphisms in human infectious diseases. HLA variation has been
      associated with susceptibility or resistance to malaria, tuberculosis, leprosy,
      AIDS, and hepatitis virus persistence. Variation in the tumor necrosis factor
      gene promoter has also been associated with several infectious diseases.
      Chemokine receptor polymorphism affects both susceptibility ot HIV-1 infection
      and the rate of progression to AIDS. Inactivating mutations of the gamma
      interferon receptor lead to increased susceptibility to typical mycobacteria and
      disseminated BCG infection in homozygous children. The active form of vitamin D
      has immunomodulatory effects, and allelic variants of the vitamin D receptor
      appear to be associated with differential susceptibility to several infectious
      diseases. NRAMP1, a macrophage gene identified by positional cloning of its
      murine homologue, has been implicated in susceptibility to tuberculosis in
      Africans. Whole genome linkage analysis of multi-case families is now being used
      to map and identify new loci affecting susceptibility to infectious diseases. It
      is likely that susceptibility to most microorganisms is determined by a large
      number of polymorphic genes, and identification of these should provide insights
      into protective and pathogenic mechanisms in infectious diseases.

PMID- 9597144
TI  - How do monoclonal antibodies induce tolerance? A role for infectious tolerance?
AB  - One of the major goals in therapeutic immunosuppression has been to achieve long
      term benefit from short-term therapy. The discovery in the mild-1980s that CD4
      antibodies can induce immunological tolerance without depleting CD4+ T cells has
      reawakened interest in the use of nondepleting monoclonal antibodies for
      reprogramming the immune system in autoimmunity and in transplantation. Since
      that time, antibodies to CD11a, CD4OL, CD25, CD3, and CTLA4-Ig have all been
      shown capable of facilitating tolerance. In order to apply to principle of
      reprogramming in the clinic, we have sought to understand the mechanisms that are
      involved in its induction and its maintenance. In a number of allogeneic
      transplant models (heart, skin, bone marrow) anti-CD4 (+/- CD8) antibodies can be
      shown to block the rejection process while selectively promoting the development
      of CD4+ regulatory T cells responsible for a dominant tolerance that is reflected
      in findings of linked suppression and infectious tolerance. In these models, T
      cells that have never been exposed to CD4 antibodies become tolerant to grafted
      antigens by experiencing antigen in the microenvironment of regulatory T cells.
      Dominant tolerance is not the only mechanism that can be facilitated by CD4 Mab
      therapy. If allogeneic marrow is given at high cell doses under the umbrella of
      CD4 and CD8 antibodies, then tolerance can be achieved through clonal deletion.
      The mechanism by which regulatory CD4+ T cell suppress is not yet defined but
      could be active or passive. We have proposed the "civil service model" to explain
      how tolerant T cells might interfere with the responses of competent T cells in
      such a way as to render them tolerant.

PMID- 9597145
TI  - Positive versus negative signaling by lymphocyte antigen receptors.
AB  - Antigen receptors on lymphocytes play a central role in immune regulation by
      transmitting signals that positively or negatively regulate lymphocyte survival,
      migration, growth, and differentiation. This review focuses on how opposing
      positive or negative cellular responses are brought about by antigen receptor
      signaling. Four types of extracellular inputs shape the response to antigen: (a)
      the concentration of antigen; (b) the avidity with which antigen is bound; (c)
      the timing and duration of antigen encounter; and (d) the association of antigen
      with costimuli from pathogens, the innate immune system, or other lymphocytes.
      Intracellular signaling by antigen receptors is not an all-or-none event, and
      these external variables alter both the quantity and quality of signaling. Recent
      findings in B lymphocytes have clearly illustrated that these external inputs
      affect the magnitude and duration of the intracellular calcium response, which in
      turn contributes to differential triggering of the transcriptional regulators NF
      kappa B, JNK, NFAT, and ERK. The regulation of calcium responses involves a
      network of tyrosine kinases (e.g. lyn, syk), tyrosine or lipid phosphatases
      (CD45, SHP-1, SHIP), and accessory molecules (CD21/CD19, CD22, FcR gamma 2b).
      Understanding the biochemistry and logic behind these integrative processes will
      allow development of more selective and efficient pharmaceuticals that suppress,
      modify, or augment immune responses in autoimmunity, transplantation, allergy,
      vaccines, and cancer.

PMID- 9597146
TI  - A quest for erythropoietin over nine decades.
AB  - The major research accomplishments of the author are described from the time of
      his PhD thesis work on the mechanism of cobalt polycythemia to the present day.
      His early work on the quest for the cell that produces erythropoietin (Epo) to
      his current work on oxygen sensing and signal transduction pathways involved in
      erythropoietin gene expression are reported. He describes his main research
      interest in the mechanism of cobalt polycythemia between 1954 and 1962 and his
      research on how hormones such as the glucocorticoids function in the regulation
      of erythropoiesis (1956-1962). His major findings during this period were the
      discovery that hydrocortisone and corticosterone stimulated erythropoiesis (1958)
      and that cobalt increased erythropoietin production in the isolated perfused dog
      kidney (1961). He describes how he was led astray in some of his early studies on
      the cells in the kidney that produce erythropoietin, because of the less
      developed technology available to him at that time; and how in situ hybridization
      and other molecular biology techniques enabled him to confirm some of the earlier
      work in mice by other investigators that interstitial cells in the kidney were
      the site of production of erythropoietin in the primate. His work in the
      controversial area of the mechanism of the anemia of end-stage renal disease is
      described in detail, as it pertains to Epo deficiency and suppressed erythroid
      progenitor cell response to Epo. He also discusses his recent work on signal
      transduction pathways (hypoxia, nitric oxide, adenosine, and C kinase) in oxygen
      sensing and Epo gene expression.

PMID- 9597147
TI  - Signal transduction in environmental neurotoxicity.
AB  - Signal transduction is the process by which specific information is transferred
      from the cell surface to the cytosol and ultimately to the nucleus, leading to
      changes in gene expression. Since these chains of biochemical and molecular steps
      control the normal function of each cell, disruption of these processes would
      have a significant impact on cell physiology. Some of the major signal
      transduction pathways are briefly reviewed. The interactions of four chemicals
      (lead, ethanol, polychlorinated biphenyls, and trimethyltin) with different cell
      signaling systems, particularly the phospholipid hydrolysis/protein kinase C
      pathway, are discussed. The possible causal relationship of such cellular and
      molecular interactions with known signs and symptoms of neurotoxicity are
      highlighted.

PMID- 9597148
TI  - Growth hormone as therapy for older men and women.
AB  - Progressive deficits in the growth hormone (GH)/insulin-like growth factor I axis
      may contribute to the acquired biochemical, body composition, and functional
      changes of normal human aging, but they do not offer a sole, or even a major
      explanation for these changes. The concept that GH "replacement" would materially
      benefit the daily function of older men and women finds little support in the
      results of the controlled clinical trials that have been reported. GH, either as
      monotherapy or in combination with antiresorptive medication, does not offer a
      clinically useful improvement in bone mass, and it is difficult to find a
      rationale for its use in the treatment of osteoporosis. GH may yet prove to be a
      useful agent for older men and women in the management of other clinical
      syndromes, such as visceral obesity, but conclusions in this area await
      compelling evidence. For the time being, potential benefits of GH in older men
      and women must be viewed with skepticism, and use of this agent outside the
      context of a clinical trial is not justified.

PMID- 9597149
TI  - Predictive value of in vitro model systems in toxicology.
AB  - The application of in vitro model systems to evaluate the toxicity of xenobiotics
      has significantly enhanced our understanding of drug- and chemical-induced target
      toxicity. From a scientific perspective, there are several reasons for the
      popularity of in vitro model systems. From the public perspective, in vitro model
      systems enjoy increasing popularity because their application may allow a
      reduction in the number of live animals employed in toxicity testing. In this
      review, we present an overview of the use of in vitro model systems to
      investigate target organ toxicity of drugs and chemicals, and provide selective
      examples of these model systems to better understand cutaneous and ocular
      toxicity and the role of drug metabolism in the hepatotoxicity of selected
      agents. We conclude by examining the value and use of in vitro model systems in
      industrial development of new pharmaceutical agents.

PMID- 9597150
TI  - Cyclooxygenases 1 and 2.
AB  - Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key
      enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991,
      several laboratories identified a product from a second gene with COX activity
      and called it COX-2. However, COX-2 was inducible, and the inducing stimuli
      included pro-inflammatory cytokines and growth factors, implying a role for COX-2
      in both inflammation and control of cell growth. The two isoforms of COX are
      almost identical in structure but have important differences in substrate and
      inhibitor selectivity and in their intracellular locations. Protective PGs, which
      preserve the integrity of the stomach lining and maintain normal renal function
      in a compromised kidney, are synthesized by COX-1. In addition to the induction
      of COX-2 in inflammatory lesions, it is present constitutively in the brain and
      spinal cord, where it may be involved in nerve transmission, particularly that
      for pain and fever. PGs made by COX-2 are also important in ovulation and in the
      birth process. The discovery of COX-2 has made possible the design of drugs that
      reduce inflammation without removing the protective PGs in the stomach and kidney
      made by COX-1. These highly selective COX-2 inhibitors may not only be anti
      inflammatory but may also be active in colon cancer and Alzheimer's disease.

PMID- 9597151
TI  - Interactions between hormones and chemicals in breast cancer.
AB  - Development of breast cancer in women is dependent on diverse factors, including
      genetic predisposition, exposure to both exogenous and endogenous chemicals,
      which can modulate initiation, promotion and progression of this disease, and the
      timing of exposure to these agents. Several compounds--including 16 alpha
      hydroxyestrone (16 alpha-OHE1), catecholestrogens, and aromatic amines--have been
      proposed as initiators of mammary carcinogenesis in humans; however, their role
      as genotoxins is unconfirmed. Lifetime exposure to estrogens has been established
      as an important risk factor for breast cancer, and it has been suggested that
      xenoestrogens may directly add to the hormonal risk or indirectly increase risk
      by decreasing 2-hydroxyestrone (2-OHE1)/16 alpha-OHE1 metabolite ratios. Results
      of recent studies suggest that chemical-induced modulation of 2-OHE1/16 alpha
      OHE1 metabolite ratios is not predictive of xenoestrogens or mammary carcinogens.
      Moreover, based on current known dietary intakes of natural and
      xenoestrogenic/antiestrogenic chemicals, it is unlikely that xenoestrogens
      contribute significantly to a woman's overall lifetime exposure to estrogens.
      More information is required on the identities and serum levels of both natural
      and xenoendocrine active compounds, their concentrations in serum, and the
      mammary gland and levels of these compounds at critical periods of exposure.

PMID- 9597152
TI  - Neuronal injury associated with HIV-1: approaches to treatment.
AB  - Mounting evidence suggests that cognitive dysfunction developing as a result of
      HIV-1 infection is mediated at least in part by generation of excitotoxins and
      free radicals in the brain. This syndrome is currently designated HIV-1
      associated cognitive/motor complex, was originally termed the AIDS Dementia
      Complex, and for simplicity, is called AIDS dementia in this review. Recently,
      brains of patients with AIDS have been shown to manifest neuronal injury and
      apoptotic-like cell death. How can HIV-1 result in neuronal damage if neurons
      themselves are only rarely, if ever, infected by the virus? Experiments from
      several different laboratories have lent support to the existence of HIV- and
      immune-related toxins in a variety of in vitro and in vivo paradigms. In one
      recently defined pathway to neuronal injury, HIV-infected macrophages and
      microglia, or immune-activated macrophages and astrocytes (activated by the shed
      HIV-1 envelope protein, gp120, or other viral proteins and cytokines), appear to
      secrete excitants and neurotoxins. These substances may include arachidonic acid,
      platelet-activating factor, free radicals (NO. and O2.-), glutamate, quinolinate,
      cysteine, amines, and as yet unidentified factors emanating from stimulated
      macrophages and reactive astrocytes. A final common pathway for neuronal
      susceptibility is operative, similar to that observed in stroke and several
      neurodegenerative diseases. This mechanism involves excessive activation of N
      methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive
      influx of Ca2+ and the generation of free radicals, leading to neuronal damage.
      With the very recent development of clinically tolerated NMDA antagonists, there
      is hope for future pharmacological intervention.

PMID- 9597153
TI  - Cannabinoid receptors and their endogenous agonists.
AB  - Marijuana has been in use for over 4000 years as a therapeutic and as a
      recreational drug. Within the past decade, two cannabinoid receptor types have
      been identified, their signal transduction characterized, and an endogenous lipid
      agonist isolated from mammalian tissues. The CB1 cannabinoid receptor is widely
      distributed in mammalian tissues, with the highest concentrations found in brain
      neurons. CB1 receptors are coupled to modulation of adenylate cyclase and ion
      channels. The CB2 receptor is found in cells of the immune system and is coupled
      to inhibition of adenylate cyclase. Both receptor types selectively bind delta 9
      THC, the active principle in marijuana, and anandamide (arachidonylethanolamide),
      an endogenous cannabimimetic eicosanoid. Progress is being made in the
      development of novel agonists and antagonists with receptor subtype selectivity,
      mice with genetic deletion of the cannabinoid receptors, and receptor-specific
      antibodies, which should help in providing a better understanding of the
      physiological role of the cannabinoid receptors.

PMID- 9597154
TI  - Presynaptic receptors.
AB  - Activation of different types of G-protein-linked and ionotropic presynaptic
      receptors has been shown to regulate neurotransmitter release throughout the
      central and peripheral nervous systems. In the case of G-protein-linked
      receptors, three major mechanisms have been suggested: (a) inhibition of Ca
      channels in the nerve terminal; (b) the activation of presynaptic K channels,
      resulting in a reduction in the effectiveness of the action potential; and (c)
      direct modulation of one or more components of the neurotransmitter vesicle
      release apparatus. In the case of ionotropic presynaptic receptors, inhibition of
      release may be achieved through depolarization of the terminal and inactivation
      of Na and Ca channels. Activation of presynaptic ionotropic receptors that are
      appreciably Ca permeable can also enhance the release of transmitters as a result
      of their ability to raise [Ca]i in the terminal directly. Many transmitters
      employ several of these mechanisms, thus allowing considerable flexibility in the
      presynaptic regulation of transmitter release.

PMID- 9597155
TI  - The pharmacology and toxicology of polyphenolic-glutathione conjugates.
AB  - Polyphenolic-glutathione (GSH) conjugates and their metabolites retain the
      electrophilic and redox properties of the parent polyphenol. Indeed, the
      reactivity of the thioether metabolites frequently exceeds that of the parent
      polyphenol. Although the active transport of polyphenolic-GSH conjugates out of
      the cell in which they are formed will limit their potential toxicity to those
      cells, once within the circulation they can be transported to tissues that are
      capable of accumulating these metabolites. There are interesting physiological
      similarities between the organs that are known to be susceptible to polyphenolic
      GSH conjugate-mediated toxicity. In addition, the frequent localization of gamma
      glutamyl transpeptidase to cells separating the circulation from a second fluid
      filled compartment coincides with tissues that are susceptible either to
      polyphenolic-GSH conjugate-induced toxicity or to quinone and reactive oxygen
      species-induced toxicity. Polyphenolic-GSH conjugates therefore contribute to the
      nephrotoxicity, nephrocarcinogenicity, and neurotoxicity of a variety of
      polyphenols.

PMID- 9597156
TI  - The mammalian carboxylesterases: from molecules to functions.
AB  - Multiple carboxylesterases (EC 3.1.1.1) play an important role in the hydrolytic
      biotransformation of a vast number of structurally diverse drugs. These enzymes
      are major determinants of the pharmacokinetic behavior of most therapeutic agents
      containing ester or amide bonds. Carboxylesterase activity can be influenced by
      interactions of a variety of compounds either directly or at the level of enzyme
      regulation. Since a significant number of drugs are metabolized by
      carboxylesterase, altering the activity of this enzyme class has important
      clinical implications. Drug elimination decreases and the incidence of drug-drug
      interactions increases when two or more drugs compete for hydrolysis by the same
      carboxylesterase isozyme. Exposure to environmental pollutants or to lipophilic
      drugs can result in induction of carboxylesterase activity. Therefore, the use of
      drugs known to increase the microsomal expression of a particular
      carboxylesterase, and thus to increase associated drug hydrolysis capacity in
      humans, requires caution. Mammalian carboxylesterases represent a multigene
      family, the products of which are localized in the endoplasmic reticulum of many
      tissues. A comparison of the nucleotide and amino acid sequence of the mammalian
      carboxylesterases shows that all forms expressed in the rat can be assigned to
      one of three gene subfamilies with structural identities of more than 70% within
      each subfamily. Considerable confusion exists in the scientific community in
      regards to a systematic nomenclature and classification of mammalian
      carboxylesterase. Until recently, adequate sequence information has not been
      available such that valid links among the mammalian carboxylesterase gene family
      or evolutionary relationships could be established. However, sufficient basic
      data are now available to support such a novel classification system.

PMID- 9597157
TI  - The role of receptor kinases and arrestins in G protein-coupled receptor
      regulation.
AB  - G protein-coupled receptors (GPRs) play a key role in controlling hormonal
      regulation of numerous second-messenger pathways. However, following agonist
      activation, most GPRs rapidly lose their ability to respond to hormone. For many
      GPRs, this process, commonly referred to as desensitization, appears to be
      primarily mediated by two protein families: G protein-coupled receptor kinases
      (GRKs) and arrestins. GRKs specifically bind to the agonist-occupied receptor,
      thereby promoting receptor phosphorylation, which in turn leads to arrestin
      binding. Arrestin binding precludes receptor/G protein interaction leading to
      functional desensitization. Many GPRs are then removed from the plasma membrane
      via clathrin-mediated endocytosis. Recent studies have implicated endocytosis in
      the resensitization of GPRs and have linked both GRKs and arrestins to this
      process. In this review, we discuss the role of GRKs and arrestins in regulating
      agonist-specific signaling and trafficking of GPRs.

PMID- 9597158
TI  - From GABAA receptor diversity emerges a unified vision of GABAergic inhibition.
AB  - Transmitter receptor diversity often indicates differences in transmitter
      receptor transduction mechanisms. This is not the case for gamma-aminobutyric
      acid subtype A (GABAA) receptor subtypes despite the presence of 16 genes to
      encode the 5 families of native GABAA receptor subtypes. Similar considerations
      apply to GABAC receptors and GABAB receptors. Both GABAA and GABAB receptors
      cause hyperpolarization of neuronal membranes and inhibition of neuronal
      excitability, but their mechanisms differ. GABAB receptors involve an efflux of
      K+ rather than an influx of Cl-, as in the case of GABAA and GABAC receptors. The
      stimulation of GABAA receptors can sometimes cause depolarization by Cl- efflux;
      this efflux is not the result of a transduction mechanism modification, but of
      Cl(-)-concentration gradient modification. Presumably, GABAA receptor diversity
      is directly linked to the inhibitory activity of basket cells and other
      interneuron axons, each innervating several postsynaptic neurons (cortical and
      hippocampal pyramidal cells for instance). Since the role of this inhibition is
      to entrain hippocampal and cortical pyramidal neurons into columnary activity,
      the GABAA receptor diversification may be a mechanism expressed by these
      postsynaptic neuron populations that uses different GABA potencies to synchronize
      pyramidal neurons into columnary activity. Thus, GABA potency variability, which
      emerges from GABAA receptor diversity, plays a unifying role in the intrinsic
      functional mechanism of laminated structures. GABAA receptor structural
      differences also play a role in diazepam tolerance, which is a mechanism
      operative in neuronal circuit adaptation to the extreme amplification of GABA
      gated Cl- current intensities. Partial agonists (such as imidazenil), which
      modestly amplify GABA action at many GABAA receptor subtypes, fail to cause
      tolerance, dependence, ataxia, or ethanol and barbiturate potentiation. Partial
      agonists might become a new class of anxiolytic and anticonvulsant drugs that are
      virtually devoid of the side effects that cause serious concerns in the clinical
      use of full allosteric positive modulators of GABA action, such as diazepam,
      alprazolam, triazolam, and others. None of the above can be used as
      anticonvulsants because of an extremely high tolerance liability. When there is
      tolerance to diazepam, signs of sensitization to proconvulsive action are
      exhibited simultaneously. After tolerance, associated changes in GABAA recepter
      subtype expression are virtually reversed in 72 h. Also, 96 h after termination
      of long-term diazepam treatment, rats exhibit anxiety and are more sensitive to
      kainic acid-elicited convulsions. At the same time, these rats have an increase
      in brain expression of GLuR1, R2, and R3. It is believed that the
      supersensitivity to kainic acid, convulsions and anxiety, and the increased
      expression of GLuR1, R2, and R3 may be parts of the mechanism of diazepam
      dependence.

PMID- 9597159
TI  - Insights from in vivo modification of adrenergic receptor gene expression.
AB  - Adrenergic receptors are key targets within the autonomic nervous system,
      regulating a wide variety of physiological processes. The ability to modify
      adrenergic receptor expression patterns in vivo has added a powerful new tool to
      the functional analysis of these receptors. Modification of adrenergic receptor
      gene expression by overexpression, genetic ablation, or site-specific mutation
      has added new insight to models of receptor coupling behavior, pharmacology, and
      subtype-specific physiological function. This review highlights some of the
      recent advances resulting from such genetic approaches to the study of adrenergic
      receptors.

PMID- 9597160
TI  - Mechanisms of action of bisphosphonates.
AB  - Bisphosphonates (BPs) are pyrophosphate analogs in which the oxygen bridge has
      been replaced by carbon and diverse carbon side chains have generated a large
      family of compounds. Several are potent inhibitors of bone destruction
      (resorption) and are in clinical use for the treatment and prevention of
      osteoporosis, Paget's disease, hypercalcemia caused by malignancy, tumor
      metastases in bone, and other bone ailments. Selective action on bone is based on
      the binding of the BP moiety to the bone mineral. The molecular mode of action of
      BPs, which may differ from compound to compound, is unknown. However, at the
      tissue level, all BPs inhibit bone destruction and lead to an increase in bone
      mineral density by decreasing bone resorption and bone turnover. At the cellular
      level, the ultimate target of BP action is the osteoclast, the bone resorbing
      cell. In vitro evidence shows BP inhibition of osteoclast formation, via action
      on osteoblasts, and there is in vitro and in vivo evidence for BP inhibition of
      osteoclast activity. There is in vivo and in vitro evidence for increased
      apoptosis. The relative contribution of these various effects on the therapeutic
      action of BPs remains to be established. At the molecular level, it is not known
      if BPs act on a single or multiple targets. Enzymes in the cholesterol
      biosynthesis pathway and protein tyrosine phosphatases were shown to be inhibited
      by BPs.

PMID- 9597161
TI  - In vitro and in vivo drug interactions involving human CYP3A.
AB  - Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many
      chemically diverse drugs administered to humans. Moreover, its localization in
      high amounts both in the small intestinal epithelium and liver makes it a major
      contributor to presystemic elimination following oral drug administration. Drug
      interactions involving enzyme inhibition or induction are common following the
      coadministration of two or more CYP3A substrates. Studies using in vitro
      preparations are useful in identifying such potential interactions and possibly
      permitting extrapolation of in vitro findings to the likely in vivo situation.
      Even if accurate quantitative predictions cannot be made, several classes of
      drugs can be expected to result in a drug interaction based on clinical
      experience. In many instances, the extent of such drug interactions is
      sufficiently pronounced to contraindicate the therapeutic use of the involved
      drugs.

PMID- 9597162
TI  - Role of organic cation transporters in drug absorption and elimination.
AB  - Organic cation transporters are critical in drug absorption, targeting, and
      disposition. It has become increasingly clear that multiple mechanisms are
      involved in organic cation transport in the key tissues responsible for drug
      absorption and disposition: the kidney, liver, and intestine. In this review, we
      discuss current models of transepithelial flux of organic cations in these three
      tissues. Particular emphasis is placed on the more recent molecular studies that
      have paved the way for a more complete understanding of the physiological and
      pharmacological roles of the organic cation transporters. Such information is
      essential in predicting pharmacokinetics and pharmacodynamics and in the design
      and development of cationic drugs.

PMID- 9597163
TI  - Quantitative prediction of in vivo drug clearance and drug interactions from in
      vitro data on metabolism, together with binding and transport.
AB  - It is of great importance to predict in vivo pharmacokinetics in humans based on
      in vitro data. We summarize recent findings of the quantitative prediction of the
      hepatic metabolic clearance from in vitro studies using human liver microsomes,
      hepatocytes, or P450 isozyme recombinant systems. Furthermore, we propose a
      method to predict pharmacokinetic alterations caused by drug-drug interactions
      that is based on in vitro metabolic inhibition studies using human liver
      microsomes or human enzyme expression systems. Although we attempt to avoid the
      false negative prediction, the inhibitory effect was underestimated in some
      cases, indicating the possible contribution of the active transport into
      hepatocytes and/or interactions at the processes other than the hepatic
      metabolism, such as the metabolism and transport processes during
      gastrointestinal absorption.

PMID- 9597164
TI  - Glutathione-dependent bioactivation of haloalkenes.
AB  - Several halogenated alkenes are nephrotoxic in rodents. A mechanism for the organ
      specific toxicity of these compounds to the kidney has been elucidated. The
      mechanism involves hepatic glutathione conjugation to dihaloalkenyl or 1,1
      difluoroalkyl glutathione S-conjugates, which are cleaved by gamma
      glutamyltransferase and dipeptidases to cysteine S-conjugates. Haloalkene-derived
      cysteine S-conjugates may have four fates in the organism: (a) They may be
      substrates for renal cysteine conjugate beta-lyases, which cleave them to form
      reactive intermediates identified as thioketenes (chloroalkene-derived S
      conjugates), thionoacyl halides (fluoroalkene-derived S-conjugates not containing
      bromide), thiiranes, and thiolactones (fluoroalkene-derived S-conjugates
      containing bromine); (b) cysteine S-conjugates may be N-acetylated to excretable
      mercapturic acids; (c) they may undergo transamination or oxidation to the
      corresponding 3-mercaptopyruvic acid S-conjugate; (d) finally, oxidation of the
      sulfur atom in halovinyl cysteine S-conjugates and corresponding mercapturic
      acids forms Michael acceptors and may also represent a bioactivation reaction.
      The formation of reactive intermediates by cysteine conjugate beta-lyase may play
      a role in the target-organ toxicity and in the possible renal tumorigenicity of
      several chlorinated olefins widely used in many chemical processes.

PMID- 9597165
TI  - Ethnopharmacology of Mexican asteraceae (Compositae).
AB  - Traditional herbal remedies have increased in popularity in Europe and the United
      States in recent years but have always been important to people living in rural
      Mexico and to their Mexican American/Chicano descendants in the United States.
      Mexican American patients will often be ingesting herbal teas at the same time
      that they are being treated for their ailments with antibiotics or
      antiinflammatory agents. The plant family Asteraceae (Compositae) has contributed
      the largest number of plants to this pharmacopoeia; the reasons for the
      importance of this family include its large number of species in Mexico and its
      wide array of natural products that are useful in the treatment of the maladies
      that have afflicted the inhabitants of rural Mexico. These natural products
      include sesquiterpene lactones, polyacetylenes, alkaloids, monoterpenes, and
      various phenolics such as flavonoids. In this review, we emphasize the
      sesquiterpene lactones, a large group of compounds with antiinflammatory
      properties and the ability to relax smooth muscles and thereby relieve
      gastrointestinal distress. These compounds also readily form adducts with
      glutathione or free thiols and can thereby affect the metabolism, activity, and
      toxicology of a wide array of pharmacological agents.

PMID- 9597166
TI  - The significance of trace elements for human health and well-being.

PMID- 9597167
TI  - Trace element intake in Europe: safe and adequate?

PMID- 9597168
TI  - Trace element deficiencies in man.

PMID- 9597169
TI  - Trace element bioavailability.

PMID- 9597170
TI  - Improvement of trace element status through food fortification: technological,
      biological and health aspects.

PMID- 9597171
TI  - Iodine status of Austrian children and adolescents.

PMID- 9597172
TI  - The effects of iron supplementation on cognitive function in infants and
      children.

PMID- 9597173
TI  - Effect of zinc supplementation on children's growth: a meta-analysis of
      intervention trials.

PMID- 9597174
TI  - Micronutrients, minerals and growth control.
AB  - (1) Dietary deficiencies of Zn, Mg and K lead to a rapid drop in serum
      concentrations, with no change (Zn) or a slow decline (Mg and K) in the
      concentrations in skeletal muscle. (2) These deficiencies all lead to inhibition
      of growth and protein synthesis in muscle. (3) The inhibition of protein
      synthesis is faster in onset than the loss of Zn, Mg and K from muscle and
      therefore unlikely to result from cellular mineral deficiency. (4) The
      deficiencies are likely to be detected by the early drop in serum concentration,
      but the mechanism is unknown. (5) Possible mediators of growth inhibition are
      anorexia, GH and IGF-I. (6) Early detection of mineral deficiencies allows the
      organism to minimize wasteful protein synthesis and the formation of functionally
      inadequate tissues.

PMID- 9597175
TI  - Zinc metabolism during pregnancy--interactions with vitamin A.

PMID- 9597176
TI  - Roles of trace metals in the maturation, activation and effector functions of
      immune cells.

PMID- 9597177
TI  - Excessive intake of iron and mercury in cardiovascular disease.

PMID- 9597178
TI  - Trace elements and cardiovascular disease.

PMID- 9597179
TI  - Selenium and cancer.

PMID- 9597180
TI  - Trace elements and bone metabolism.

PMID- 9597181
TI  - Structural comparison of 1 beta-methylcarbapenem, carbapenem and penem: NMR
      studies and theoretical calculations.
AB  - Structural comparisons of meropenem (1), desmethyl meropenem (2) and the penem
      analogue (3) which contain the same side chains at both C-2 and C-6 were
      performed using 1H NMR measurements together with 3-21G* level of ab initio MO
      and molecular mechanics calculations. The ab initio MO calculations reproduced
      the skeletons of these strained beta-lactam rings in good agreement with the
      crystallographic data. 1H NMR measurements in aqueous solution together with
      molecular modeling studies indicated that there were conformational differences
      of the C-2 and C-6 side chains in this series of compounds. These observations
      suggested that the conformational differences could affect their biological
      activities.

PMID- 9597182
TI  - Comparative molecular field analysis of non-steroidal aromatase inhibitors: an
      extended model for two different structural classes.
AB  - Aromatase is a cytochrome P450 isozyme, whose inhibition is known to be
      therapeutically relevant in the treatment of the breast cancer. A comparative
      molecular field analysis (CoMFA) has been carried out on a series of non
      steroidal aromatase inhibitors belonging to two different structural classes. One
      subset of compounds consists of fadrozole analogues and was studied in a previous
      work, from which a 'local' 3-D quantitative structure-activity relationship
      (QSAR) model for the inhibition of aromatase was obtained. In the present paper,
      that model is extended to include a second subset of compounds bearing a
      tetralone nucleus and acting at the same enzyme site with the same mechanism as
      the azoles. The critical alignment step has been solved by using two different
      steroidal inhibitors of aromatase as rigid templates, on which the non-steroidal
      compounds have been superimposed. The final 3-D QSAR models are discussed in
      terms of predictivity and some implications regarding the steric and electronic
      requirements of steroidal and non-steroidal inhibitors are pointed out.

PMID- 9597183
TI  - High affinity central benzodiazepine receptor ligands: synthesis and structure
      activity relationship studies of a new series of pyrazolo[4,3-c]quinolin-3-ones.
AB  - A large series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin- 3-(3H)
      ones, carrying appropriate substituents at the quinoline and N2-phenyl rings,
      were prepared and tested as central benzodiazepine receptor ligands. Results from
      structure-affinity relationship studies were in full agreement with previously
      proposed pharmacophore models and, in addition, quantitative structure-activity
      analysis gave further significant insight into the main molecular determinants of
      high benzodiazepine receptor affinity. The intrinsic activity of some active
      ligands was also determined and preliminary discussed.

PMID- 9597184
TI  - Synthesis of new delta 2-isoxazoline derivatives and their pharmacological
      characterization as beta-adrenergic receptor antagonists.
AB  - A series of delta 2-isoxazoline derivatives structurally related to Broxaterol 1
      and Falintolol 3 has been prepared and evaluated for their binding affinity to
      beta 1- and beta 2-adrenergic receptors. Among the tested compounds only the 3
      isopropenyl anti derivative 4d is as active as the reference compounds. An
      electron-releasing group, probably operating through a pi-pi interaction, in the
      3-position of the isoxazoline nucleus greatly enhances the affinity of the
      compounds. Conversely, the closest analogs of Broxaterol (3-bromo delta 2
      isoxazolines 4a and 5a) are at least one order of magnitude less active than the
      model compound 1. Throughout the series of derivatives the anti stereoisomers are
      invariably more active than their syn counterparts.

PMID- 9597185
TI  - Synthesis of 2,6-dioxo-(1H,3H)-9-N-ribitylpurine and 2,6-dioxo-(1H,3H)-8-aza-9-N
      ribitylpurine as inhibitors of lumazine synthase and riboflavin synthase.
AB  - 2,6-Dioxo-(1H,3H)-9-N-ribitylpurine (6) and 2,6-dioxo-(1H,3H)-8-aza-9-N
      ribitylpurine (7) have been synthesized and evaluated as inhibitors of lumazine
      synthase and riboflavin synthase. Reaction of 5-amino-6-ribitylaminouracil
      hydrochloride (8) with diethoxymethyl acetate (9) afforded the purine 6, while
      diazotization of 8 afforded the 8-aza purine 7. Compounds 6 and 7 were evaluated
      against lumazine synthase of Bacillus subtilis and riboflavin synthase of
      Escherichia coli. Both 6 and 7 were better inhibitors of lumazine synthase than
      riboflavin synthase. The 8-azapurine 7 had a lower KI (0.33 and 0.39 mM) than the
      purine 6 (0.47 and 0.54 mM) when evaluated with lumazine synthase and riboflavin
      synthase, respectively.

PMID- 9597186
TI  - Coumarin-based prodrugs. Part 3: Structural effects on the release kinetics of
      esterase-sensitive prodrugs of amines.
AB  - To study the structural effects on the release kinetics of a coumarin-based
      esterase-sensitive prodrug system, two series of compounds with varying
      structural features of the ester 'trigger' part and the amine 'drug' part were
      synthesized. The half-lives of the nine model prodrugs in the presence of porcine
      liver esterase ranged from about 2 min to 190 min. The steric bulkiness of the
      acyl group seems to have only a very minor effect on the half-lives of the
      esterase-triggered release of amines from the model prodrugs. The rate of the
      lactonization depends on the steric and electronic properties of the amine
      moiety.

PMID- 9597187
TI  - Synthesis and evaluation of tacrine-huperzine A hybrids as acetylcholinesterase
      inhibitors of potential interest for the treatment of Alzheimer's disease.
AB  - Seventeen polycyclic compounds related to tacrine and huperzine A have been
      prepared as racemic mixtures and tested as acetylcholinesterase (AChE)
      inhibitors. The conjunctive pharmacomodulation of huperzine A (carbobicyclic
      substructure) and tacrine (4-aminoquinoline substructure) led to compound 7jy,
      2.5 times less active than tacrine as AChE inhibitor, but much more active than
      its (Z)-stereoisomer (7iy). Derivatives 7dy and 7ey, lacking the ethylidene
      substituent, showed to be more active than tacrine. Many other structural
      modifications of 7jy led to less active compounds. Compounds 7dy and 7ey also
      showed to be much more active than tacrine in reversing the partial neuromuscular
      blockade induced by d-tubocurarine.

PMID- 9597188
TI  - New orally active enkephalinase inhibitors: their synthesis, biological activity,
      and analgesic properties.
AB  - A series of (4S)-4-[(2S)-benzyl-3-mercaptopropionylamino]-4-(N-phenylcarbamoyl )
      butyric acids has been identified as potent systemically active enkephalinase
      inhibitors. Structure-activity relationships (SAR) are discussed. Further
      chemical modification of the inhibitors was carried out in order to identify the
      inhibitors which are orally active in an animal model. Compounds of particular
      interest are the prodrug-like analogues, including 5b (ONO-9902). Their analgesic
      effects after oral administration were evaluated.

PMID- 9597189
TI  - Structural study on silkworm eclosion hormone fragment (1-34) in solution by
      proton nuclear magnetic resonance spectroscopy.
AB  - Eclosion hormone (EH) is a neuropeptide hormone which controls the ecdysis
      behavior in insect. The three dimensional structure of the N-terminal fragment (1
      34) of the eclosion hormone which was predicted to contain a compact region
      crucial for the EH activity was studied in 50% d3-trifluoroethanol(TFE)/50% H2O
      at pH 3 and 298 K by 1H NMR spectroscopy with the combined use of distance
      geometry and molecular dynamics calculations. NMR results indicated that the
      fragment actually assumes an alpha-helix between Ala10 and Gln20, but no rigid
      structure is present from Cys21 through the C-terminus and for the N-terminal
      region (Ser1-Asp9). The elucidated structure was compared with the predicted
      structure of the native EH for the further development of the design of the
      insecticide.

PMID- 9597190
TI  - Downsizing of an HIV-cell fusion inhibitor, T22 ([Tyr5,12, Lys7]-polyphemusin
      II), with the maintenance of anti-HIV activity and solution structure.
AB  - T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have strong anti-human
      immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'
      dideoxythymidine (AZT). T22, an 18-residue peptide amide, takes an antiparallel
      beta-sheet structure that is maintained by two disulfide bridges. Herein we
      synthesized several shortened analogs of T22 in order to search for a more
      suitable lead compound. A 14-residue analog having one disulfide bridge, TW70
      (des-[Cys8,13, Tyr9,12]-[D-Lys10, Pro11]-T22), was found to have highly potent
      activity comparable to that of T22, and to take an antiparallel beta-sheet
      structure similar to that of T22. This indicates that the molecular size of T22
      can be reduced without loss of activity or significant change in the secondary
      structure, and that TW70 may represent a novel lead compound. Furthermore,
      modifying the N-terminal alpha-amino group of TW70 with a
      fluoresceinthiocarbamoyl group, and the epsilon-amino group of D-Lys8 at the turn
      portion with a 5-aminopentanoyl group remarkably increased the selectivity index
      (50% cytotoxic concentration/50% effective concentration).

PMID- 9597191
TI  - Picrodendrin and related terpenoid antagonists reveal structural differences
      between ionotropic GABA receptors of mammals and insects.
AB  - Twenty-eight picrotoxane terpenoids, including picrodendrins isolated from the
      Euphorbiaceae plant, Picrodendron baccatum (L.) Krug and Urban, have been
      evaluated for their ability to inhibit the specific binding of [3H]EBOB, the
      noncompetitive antagonist of ionotropic GABA receptors, to rat-brain and housefly
      (Musca domestica L.)-head membranes. Picrodendrin Q was the most potent
      competitive inhibitor of [3H]EBOB binding, with IC50 values of 16 nM (rat) and 22
      nM (Musca). We find that the spiro gamma-butyrolactone moiety at the 13-position,
      which contains a carbonyl group conjugated with an unsaturated bond, and the
      substituents at the 4-position play important roles in the interaction of
      picrodendrins with their binding site in rat receptors. In contrast, such
      structural features are not strictly required in the case of the interaction with
      Musca receptors; the spiro saturated gamma-butyrolactone moiety at the 13
      position, which bears the 16-sp3 carbon atom, and the hydroxyl groups at various
      positions are somewhat tolerated. Quantitative structure-activity studies have
      clearly shown that the electronegativity of the 16-carbon atom and the presence
      or absence of the 4- and 8-hydroxyl groups are important determinants of the
      potency of nor-diterpenes in Musca receptors, while the negative charge on the 17
      carbonyl oxygen atom is likely important in the case of rat receptors. These
      findings indicate that there are significant differences between the structures
      of the complementary binding sites in rat GABA receptors and Musca GABA
      receptors. We also infer differences between native Musca GABA receptors and the
      Drosophila Rdl subunit-containing homo-oligomeric GABA receptors in the
      structures of their binding sites.

PMID- 9597192
TI  - CH/pi interactions as demonstrated in the crystal structure of guanine-nucleotide
      binding proteins, Src homology-2 domains and human growth hormone in complex with
      their specific ligands.
AB  - The CH/pi interaction is a weak attractive molecular force occurring between CH
      groups and pi-systems. Possibility has been examined for the role of CH/pi
      interaction, by use of a computer program, in the crystallographic data of
      several guanine-nucleotide binding proteins, src homology-2 domains and human
      growth hormone complexed with their specific ligands. Short CH/pi contacts have
      been found in every case where cohesive forces are expected. Comparison of the
      structures of functionary related proteins has shown that mutation may occur but
      necessary CH/pi interactions are conserved. A considerable part of the non-polar
      interactions, broadly ascribed in the past to the van der Waals interaction or
      the so-called hydrophobic effect, has been suggested to be attributed to a more
      specific attractive force, the CH/pi interaction.

PMID- 9597193
TI  - Pathogenesis and management of paroxysmal nocturnal haemoglobinuria.
AB  - Over the past 30 years, our understanding of the pathogenesis of paroxysmal
      nocturnal haemoglobinuria (PNH) has increased dramatically. During that time, the
      events during complement activation and regulation have been described, the
      molecular basis for the exaggerated complement sensitivity of PNH cells has been
      uncovered, and the responsible gene mutation has been identified. It is now
      possible to relate almost all the protean manifestations of PNH to a single gene
      mutation in a haematopoietic stem cell. Unfortunately, our ability to manage
      these patients has not kept pace, and, with the exception of bone marrow
      transplantation, our major efforts are still directed toward control of
      complications rather than interruption of the disease process.

PMID- 9597194
TI  - The use of aspirin in polycythaemia vera and primary thrombocythaemia.
AB  - In polycythaemia vera (PV; polycythaemia rubra vera, primary proliferative
      polycythaemia) and primary thrombocythaemia (PT; essential thrombocythaemia),
      occlusive complications in the microvasculature and larger vessels are a
      significant cause of morbidity and mortality. Central to the pathogenesis of
      these complications are the quantitative and qualitative platelet changes present
      in these myeloproliferative disorders. Aspirin irreversibly inactivates cyclo
      oxygenase in platelets. This leads to a reduced production of platelet
      thromboxane A2 which has vasoconstricting and platelet aggregatory properties. In
      haematologically normal individuals, aspirin has been shown to reduce thrombo
      embolic complications in populations at risk of these events. In PV and PT,
      aspirin has been shown to specifically eliminate the micro-circulatory and
      vasomotor manifestations and there is some evidence of a reduction in larger
      vessel occlusion. Low-dose aspirin has been shown to substantially reduce the
      raised thromboxane A2 production of platelets in PV and PT patients. The
      incidence of haemorrhagic side-effects of aspirin are minimized by the use of low
      doses. Haemorrhagic events are particularly found in patients with platelet
      counts > 1000 x 10(9)/l and these events are enhanced by aspirin therapy in these
      patients. Aspirin should be used with caution in patients with dyspeptic symptoms
      or a history of peptic ulceration or bronchospasm. Precise PCV control (< 0.45)
      and cytoreduction (platelets < 400 x 10(9)/l) should be used in patients with PV
      to minimize the vascular occlusion risk but routine cytoreduction is proposed
      only for those at particular risk of vascular occlusion in PT. In the acute
      presentation of patients with vascular occlusion, cytoreduction and an aspirin
      dose of 300 mg a day is proposed, reducing to 75 mg a day with the control of
      symptoms and signs, while 75 mg a day may play a role as prophylactic therapy in
      the prevention of thrombosis. However, there are no prospective studies in PT to
      demonstrate the benefit/risk profile and to confirm these recommendations, while
      a randomized prospective placebo-controlled study of low-dose aspirin in PV has
      only recently been initiated.

PMID- 9597195
TI  - Hyperhomocysteinaemia and vascular disease.
AB  - The amino-acid homocysteine plays a crucial role in cell metabolism. It
      participates in the remethylation pathway enabling maintenance of adequate
      cellular levels of methionine or is catabolized by transsulphuration. A number of
      hereditary defects in the enzymes involved in homocysteine metabolism and
      acquired deficiencies in the vitamin cofactors of these enzymes are associated
      with the development of hyperhomocysteinaemia. The association between high
      circulating homocysteine levels and premature vascular thrombosis is well
      established in individuals with hereditary homocystinuria. There is now good
      epidemiological evidence that mild hyperhomocysteinaemia is an independent risk
      factor in the development of arterial disease and venous thrombosis although the
      causes of the elevated plasma homocysteine are unclear. A good candidate is
      homozygosity for the common thermolabile variant of methylenetetrahydrofolate
      reductase but the evidence for a causative association is conflicting. A number
      of in vitro effects of homocysteine on vascular endothelium, platelets and
      coagulation have been described which may predispose to vascular disease but the
      exact in vivo mechanisms remain to be elucidated. Dietary folate supplementation
      may normalize homocysteine in hyperhomocysteinaemic individuals and modify the
      risk of vascular disease.

PMID- 9597196
TI  - Management of oral anticoagulant-induced intracranial haemorrhage.
AB  - Intracranial haemorrhage is an infrequent but often fatal complication of oral
      anticoagulant therapy which will become more common as anticoagulant use
      increases. The risk of anticoagulant-induced intracranial haemorrhage may be
      reduced by judicious prescribing, identification of patients at high risk of
      bleeding, and close monitoring by experienced staff. The presenting features of
      intracranial haemorrhage are often vague and physicians should be aware of the
      need for urgent investigation of all anticoagulated patients with neurological
      symptoms. Current guidelines for immediate reversal of anticoagulation recommend
      administration of vitamin K1 and factor replacement with either factor
      concentrates or fresh frozen plasma. In this review we discuss recent evidence
      suggesting prothrombin complex concentrates lead to faster, and more complete,
      correction of coagulation and, in the context of intracranial bleeding, may be
      associated with improved neurological status. Evidence for the risks of short
      term cessation of anticoagulants, in the immediate period following an
      intracranial haemorrhage, and their subsequent reintroduction is also discussed.

PMID- 9597197
TI  - Hemorrhagic and thrombotic disorders due to factor V deficiencies and
      abnormalities: an updated classification.
AB  - The recent description of a factor V abnormality (factor V Leiden) associated
      with an increased incidence of thrombosis has considerably increased interest in
      this clotting factor. The discovery of this new clinical entity indicated the
      need for an updated classification of factor V defects. These should be divided
      into hemorrhagic and thrombotic disorders. A proper classification of hemorrhagic
      disorders should include: 1) homozygous and heterozygous 'true' factor V
      deficiency; and 2) combined factor V and factor VIII deficiencies. The latter
      should be subdivided in Type I (association type) and Type II (common defect). A
      suitable classification of the thrombotic factor V defects should include: 1)
      homozygous and heterozygous factor V Leiden; and 2) combined heterozygous factor
      V Leiden and heterozygous 'true' factor V deficiency. The presence of thrombosis
      in these latter patients, often as severe as those seen in homozygous patients
      with activated protein C (APC) resistance, allows important considerations on the
      functions of factor V. It would seem that half the normal level of factor V
      activity and antigen is unable to protect against thrombosis in patients with
      heterozygous APC resistance. An accurate evaluation of factor V activity and
      antigen is indicated in all patients with suspected factor V defects. The first
      suspicion may be obtained by the presence of a mild prolongation of prothrombin
      time and of partial thromboplastin time. The suspicion should then be immediately
      confirmed by specific factor V activity and antigen assays. This approach is of
      great importance even for the presumptive diagnosis of pseudohomozygosis for APC
      resistance. In fact, in these cases, factor V activity is about 50% of normal,
      whereas factor V antigen is 100% of normal. In heterozygous 'true' factor V
      deficiency both activity and antigen are about 50% of normal.

PMID- 9597198
TI  - Anthracyclines in haematology: pharmacokinetics and clinical studies.
AB  - The activity of anthracyclines in the treatment of a wide spectrum of
      haematological malignancies has long been established. Differences in the
      pharmacokinetic and pharmacodynamic properties of these drugs have resulted in
      the selection of individual compounds for particular indications while the recent
      reformulation of anthracyclines in liposomal preparations seems likely to
      significantly alter their range of activity and toxicity. The problems related to
      cumulative cardiotoxicity secondary to anthracycline exposure can be ameliorated
      by the use of dexrazoxane and a number of agents may prove to have a role in
      altering their cellular resistance to their cytotoxic actions.

PMID- 9597199
TI  - Intrathecal drug spread.

PMID- 9597200
TI  - Postoperative pain--a challenge for anaesthetists in ambulatory surgery.

PMID- 9597201
TI  - Densities of cerebrospinal fluid and spinal anaesthetic solutions in surgical
      patients at body temperature.
AB  - PURPOSE: To determine the densities of cerebrospinal fluid (CSF) in patients for
      surgery under spinal anaesthesia. The densities of the CSF were compared with the
      densities of local anaesthetic solutions and their mixtures with commonly used
      spinal opioids. METHOD: One ml of CSF was collected from 131 consecutive patients
      that consented to the study at the time of spinal anaesthesia. Densities were
      measured at 37 degrees C in a Density Meter that displayed density to the fourth
      decimal point and was accurate to 0.00003 g.ml-1. The densities of a selection of
      spinal anaesthetic drugs were also measured. RESULTS: The mean CSF density in the
      study population was 1.00059 +/- SD 0.00020. In men of all ages, the mean CSF
      density was 1.00067 +/- 0.00018 g.ml-1; in postmenopausal women 1.00060 +/-
      0.00015 g.ml-1; in premenopausal non-pregnant women 1.00047 +/- 0.00076 g.ml-1;
      and in pregnant women 1.00033 +/- 0.00010 g.ml-1. There were differences between
      the CSF densities in pregnant women compared with men (P = 0.0001),
      postmenopausal women (P = 0.0001) and non-pregnant premenopausal women (P =
      0.03). Local anaesthetic solutions that contain sugar (glucose or dextrose) were
      all hyperbaric. In the absence of sugar, all local anaesthetic solutions were
      hypobaric except for lidocaine CO2 which was slightly hyperbaric. Opioids were
      all hypobaric except meperidine which was hyperbaric. CONCLUSION: Pregnant women
      have slightly lower CSF densities than do men and postmenopausal women, and non
      pregnant premenopausal women. In the absence of sugar all spinal anaesthetic
      solutions measured were hypobaric except for lidocaine CO2 and meperidine, both
      of which were hyperbaric.

PMID- 9597202
TI  - Severity and impact of pain after day-surgery.
AB  - PURPOSE: To assess the intensity, duration and impact of pain after day-surgery
      interventions. Predictors of pain severity were also evaluated along with the
      quality of analgesic practices and patient satisfaction. METHODS: Eighty-nine
      consecutive day-surgery patients completed self-administered questionnaires
      before leaving the hospital and at 24, 48 hr and seven days after discharge. The
      survey instrument was composed of 0-10 pain intensity scales, selected items of
      the Brief Pain Inventory, of the Patient Outcome Questionnaire and of the
      Barriers Questionnaire. Analgesic intake in hospital and at home was recorded
      along with the use of other pain control methods. RESULTS: Forty percent of the
      patients reported moderate to severe pain during the first 24 hr after hospital
      discharge. The pain decreased with time but it was severe enough to interfere
      with daily activities in a substantial number of patients. The best predictor of
      severe pain at home was inadequate pain control during the first few hours
      following the surgery. More than 80% of the participants were satisfied with
      their pain treatment. However, one patient in four (25%) needed contact with a
      health care provider because of pain at home. Many patients (33% to 51%) reported
      that instructions about pain control were either unclear or non-existent on
      several aspects. Medication use was low overall. Thirty-two percent of the
      patients did not take any pain medication during the first 24 hr after discharge
      although almost half of them (46%) rated their pain > or = 4. The most common
      concerns patients had about using pain medication were fear of drug addiction and
      side effects. CONCLUSION: The severity and duration of pain after day-surgery
      should not be underestimated. Aggressive analgesic treatment during the hospital
      stay should be provided along with take-home analgesia protocols and
      comprehensive patient education programs.

PMID- 9597203
TI  - [Assessment of intubation time and conditions under the influence of rocuronium].
AB  - PURPOSE: To evaluate the tracheal intubating conditions when intubation time is
      determined by the onset time of the neuromuscular block either of the adductor
      pollicis (AP) or of the orbicularis oculi muscle (OO). METHODS: In this
      prospective, double blind, randomised study, 40 adults ASA I-II undergoing
      general anaesthesia with tracheal intubation were allocated to two groups (n =
      20) according to the reference muscle (AP or OO) used to determine the
      appropriate intubation time. Induction of anaesthesia was achieved with 5-7 mg.kg
      1 thiopentone, 1.5-2.5 micrograms.kg-1 fentanyl and 0.9 mg.kg-1 rocuronium (3 x
      ED95) for muscular relaxation. Supramaximal train of four stimulation of the
      ulnar and facial nerve every 10 sec was used to monitor the neuromuscular block.
      After visual loss of AP or OO contraction, tracheal intubation and quality of
      intubation assessment were performed by two independent anaesthetists. Data are
      expressed as mean and standard error of the mean (X +/- SEM). RESULTS:
      Curarisation time of the OO was shorter (110 +/- 4.9 sec) than that of the AP
      (144 +/- 5.5 sec; P < 0.0001). Intubation conditions were excellent in 95% and
      good in 5% of the patients in the AP group whereas in the OO group only 65% of
      the patients had excellent and 20% good intubation conditions (P < 0.05).
      Coughing was observed in 15% of patients in the OO group during tracheal
      intubation. CONCLUSION: Monitoring neuro-muscular activity of the AP using TOF to
      determine the appropriate tracheal intubation time and conditions in patients
      paralysed with rocurorium is more clinically relevant than monitoring the OO
      muscle.

PMID- 9597204
TI  - Oesophageal, rectal, axillary, tympanic and pulmonary artery temperatures during
      cardiac surgery.
AB  - PURPOSE: The gradient between temperatures measured at different body sites is
      not constant; one factor which will change this gradient is rapid changes in body
      temperature. Measurement of this gradient was done in patients undergoing rapid
      changes in body temperature to establish the best site to measure temperature and
      to compare two brands of commercial tympanic thermometers. METHOD: A total of 228
      sets of temperatures were measured from probes in the oesophagus, rectum, and
      axilla and from two brands of tympanic thermometer and compared with pulmonary
      artery (PA) temperature in 18 adults during cardiac surgery. RESULTS:
      Measurements from the oesophageal site was closest to PA readings (mean
      difference 0.0 +/- 0.5 degree C) compared with IVAC tympanic thermometer (mean
      difference -0.3 +/- 0.5 degree C), Genius tympanic thermometer (mean difference 
      0.4 +/- 0.5 degree C), axillary (mean difference 0.2 +/- 1.0 degrees C) and
      rectal (mean difference -0.4 +/- 1.0 degree C) readings. When data during cooling
      were analysed separately, all sites had similar gradients from PA except for
      rectal, which was larger. On rewarming, oesophageal readings were closest to PA
      readings; tympanic readings were closer to PA than were rectal or axillary
      readings. Readings from the two brands of tympanic thermometer were equivalent.
      CONCLUSION: Oesophageal temperature is more accurate and will reflect rapid
      changes in body temperature better than tympanic, axillary, or rectal
      temperature. When oesophageal temperature cannot be measured, tympanic
      temperature done by a trained operator should become the reading of choice.

PMID- 9597205
TI  - Neuromuscular relaxants in non-cardiac surgery after cardiomyoplasty.
AB  - PURPOSE: Dynamic cardiomyoplasty is a therapeutic alternative to heart
      transplantation in irreversible cardiac insufficiency. Little information exists
      about the use of muscle relaxants in patients with cardiomyoplasty. In
      particular, it is not clear if the muscle flap is responsive to neuromuscular
      blockers. The purpose of this report is to describe the safe use of vecuronium in
      a patient with cardiomyoplasty. CLINICAL FEATURES: A 59-yr-old man, after
      cardiomyoplasty for dilated cardiomyopathy two years earlier, underwent general
      anaesthesia with fentanyl, propofol and vecuronium during surgery for intestinal
      ischaemia. Intraoperative transthoracic echocardiography showed that vecuronium
      did not affect muscle flap motion. Two days after surgery he died in septic
      shock. Post-mortem histological and immunohistochemical examination showed
      nervous degeneration of the flap probably as a result of the chronic low
      frequency pacing. There was also an increase in extrajunctional receptors and an
      alteration in junctional receptors, as demonstrated by the negative reaction to
      anti-synaptophysin antibodies, used to identify the neuromuscular plate.
      CONCLUSION: In patients undergoing non-cardiac surgery after previous
      cardiomyoplasty, muscle relaxants, such as vecuronium, may be used safely.
      Depolarising agents, such as succinylcholine, should probably be avoided because
      of the possible exaggerated actions on extrajunctional receptors.

PMID- 9597206
TI  - [Bilateral subdural hematoma following epidural anesthesia].
AB  - PURPOSE: The authors report a case of bilateral subdural hematoma (SDH) which
      occurred following epidural analgesia for labour, complicated by post dural
      puncture headache (PDPH). Physiopathological mechanisms are discussed. CLINICAL
      FEATURES: A 27-yr-old woman displayed typical PDPH following epidural
      anaesthesia. On the fifth day she was given a blood patch (BP) which proved
      immediately effective. Further developments were marked by late recurrence of
      PDPH and by administration of a second BP on the 24th day. With the aggravation
      of the headaches, the disappearance of their postural nature and with the
      appearance of transitory focal neurological signs on the 30th day, a CT-Scan was
      done and showed bilateral subdural haematoma. Following surgical drainage, the
      patient made an uneventful recovery. CONCLUSION: The presence of PDPH complicated
      by a typical neurological deterioration should prompt the anaesthetist to seek an
      immediate clinical and x-ray diagnosis in order to look for the existence of
      intracranial complications.

PMID- 9597207
TI  - Anaesthesia in a parturient with Noonan's syndrome.
AB  - PURPOSE: To report the management of labour analgesia and subsequent anaesthesia
      for postpartum bleeding in a 19-yr-old parturient with Noonan's syndrome.
      CLINICAL FEATURES: The patient presented in active labour at 36-wk gestation. She
      was known to have Noonan's syndrome and had been assessed regularly throughout
      pregnancy. Features of the syndrome exhibited by the patient included typical
      facies, chest skeletal abnormalities, pulmonary valve dysplasia, mental
      retardation and lymphoedema. In addition, she had Factor XI deficiency (0.46 mg.L
      1) and thrombocytopenia (92 x 10(9).L-1), previously unreported in a parturient
      with this syndrome. Although epidural analgesia may have been considered the
      labour analgesic technique of choice, the risk of epidural haematoma caused by
      her bleeding diathesis made this unacceptable. This risk was balanced against the
      possibility of a potentially difficult intubation due to facial abnormalities,
      should emergency operative delivery become necessary. Labour analgesia was
      provided with intravenous patient controlled opioid analgesia (fentanyl 25
      micrograms bolus, five minute lockout) despite her mental retardation. Dilatation
      and curettage required general anaesthesia after intubation with awake direct
      laryngoscopy using cautious sedation. CONCLUSION: Noonan's syndrome is
      characterised by multi-system involvement, requiring thorough preoperative
      assessment of cardiovascular, skeletal, haematological and central nervous
      systems. Clotting and platelet defects considerably restrict the possible
      analgesic and anaesthetic options for labouring patients with this syndrome.

PMID- 9597208
TI  - The use of glycopyrrolate in a case of intermediate syndrome following acute
      organophosphate poisoning.
AB  - PURPOSE: This report describes a case of organophosphate intoxication refractory
      to atropine in which glycopyrrolate was used to reduce cholinergic symptoms, and
      describes the development of intermediate syndrome, an uncommon subacute
      complication of organophosphate poisoning. CLINICAL FEATURES: A 44-yr-old woman
      presented in cholinergic crisis following malathion ingestion. Treatment was
      initiated with atropine and pralidoxime. Despite clinical signs of adequate
      atropinisation, the patient continued to have profuse bronchorrhoea, which
      resolved with glycopyrrolate. During her course in the intensive care unit, she
      displayed a subacute deterioration in neuromuscular and mental status with
      decrement-increment phenomenon on electromyography consistent with intermediate
      syndrome. The patient eventually made a complete recovery. CONCLUSION: This case
      report describes the successful use of glycopyrrolate in organophosphate
      intoxication and the development of the intermediate syndrome, characterised by
      onset of weakness of neck flexors, proximal limb muscles, and respiratory muscles
      within one to four days after poisoning. Recognition of the syndrome is important
      in light of the potential for respiratory depression requiring ventilatory
      support.

PMID- 9597209
TI  - Density determination of local anaesthetic opioid mixtures for spinal
      anaesthesia.
AB  - PURPOSE: To measure the density of hyperbaric and isobaric local anaesthetics
      before and after addition of neuroaxial opioids to define a method for
      calculating any local anaesthetic/opioid mixture density based on individual
      component densities. METHODS: Density was determined using a volumetric
      pycnometer (25.0281 +/- 0.0013 ml). The density of local anaesthetics
      (bupivacaine, lidocaine), opioids (fentanyl, morphine) and multiple
      anaesthetic/opioid mixtures were measured in quadruplicate and expressed in g.ml
      1, at 37 degrees C (mean +/- SD). Regression analysis was used to derive a
      formula for calculating the density of any anaesthetic/opioid mixture. RESULTS:
      Individual components had the following densities (g.ml-1): bupivacaine 0.75%;
      1.0252 +/- 0.0001, lidocaine 5%; 1.0249 +/- 0.0001, bupivacaine 0.5%; 0.9994 +/-
      0.0001, lidocaine 2%; 1.0000 +/- 0.0001, 50 micrograms.ml-1 fentanyl; 0.9936 +/-
      0.0001, and 0.5 mg.ml-1 morphine; 1.0001 +/- 0.0001. Using regression analysis,
      linear relationships were demonstrated between density (D) of anaesthetic/opioid
      mixture and the proportion of anaesthetic in the mixture (fractional volume of
      anaesthetic) (r = 0.9999, P < 0.001). The following formula was derived;
      DensityMixture = (DLocal anaesthetic-DOpioid) x Fractional Volume Anaesthetic +
      DOpioid. Comparison of calculated and measured densities for multiple clinically
      relevant anaesthetic/opioid mixtures showed a significant degree of correlation
      (r = 0.9996, P < 0.001). CONCLUSION: Density of spinal anaesthetic/opioid
      mixtures can be calculated from the component densities and the proportion of
      anaesthetic in the mixture.

PMID- 9597210
TI  - Precipitate formed by thiopentone and vecuronium causes pulmonary embolism.
AB  - PURPOSE: To examine the effects of a bolus injection of the precipitate formed by
      thiopentone and vecuronium on the pharmacokinetic behaviour of thiopentone,
      cardiopulmonary physiology, and lung histology. METHODS: Of 16 female rabbits
      (2.9 to 3.1 kg), eight were injected with a precipitate formed by a mixture of 5
      mg.kg-1 thiopentone and 0.67 mg.kg-1 vecuronium via the external jugular vein.
      Eight control rabbits were injected with 5 mg.kg-1 thiopentone alone. Plasma
      thiopentone concentration, systolic arterial pressure and PaO2 were measured for
      60 min after injection. Histological changes in the lungs were evaluated at one
      and 60 min. RESULTS: Maximum blood thiopentone concentration in the precipitate
      group was lower than in the control group (12.9 +/- 4.5 vs 17.0 +/- 1.6
      micrograms.ml, P < 0.05), although the half-life of thiopentone in the
      precipitate group was longer (32.3 +/- 8.5 vs 21.7 +/- 8.2 min, P < 0.05) and the
      area under the time concentration curve was similar between the two groups.
      However, the mean residence time was 28% longer in the precipitate group than in
      controls (P < 0.05). The PaO2 was lower in the precipitate group than in controls
      one minute after injection (431 +/- 27 vs 464 +/- 18 mmHg, P < 0.05) but not
      subsequently. Histologically, crystals (30-150 microns in diameter) obstructed
      small arteries in the lungs at one minute but not at 60 min after injection.
      CONCLUSION: Intravenous injection of precipitate causes pulmonary microembolism,
      with a small transient decrease in PaO2.

PMID- 9597211
TI  - Tumour necrosis factor-alpha, but not septic plasma depresses cardiac myofilament
      contraction.
AB  - PURPOSE: In sepsis, myocardial depression may be caused by mediators released as
      part of the inflammatory reaction, lumour necrosis factor alpha (TNF alpha) is
      one mediator that may contribute to this depression. In the present study, we
      contrasted the effects of TNF alpha and septic plasma fraction (SP) obtained from
      an E. coli model on contractile tension in intact and skinned canine ventricular
      trabecular (VT) preparations. The objectives were to determine whether SP or TNF
      alpha could impair contractile tension at the level of the myofilaments, and to
      determine the extent to which TNF alpha may account for myocardial depression
      found in E. coli sepsis. METHODS: Measurements of isometric tensions were made
      after TNF alpha and SP (10,000 to 30,000 MW fraction) were added to respective
      intact or skinned canine VT preparations. In the skinned preparation, trabeculae
      were chemically skinned with Triton X-100. RESULTS: Septic plasma caused a
      decrease in contraction in the intact preparation compared with preseptic plasma
      (50 +/- 7 vs 33 +/- 7%, P < 0.05), but had no effect in the skinned preparation.
      On the other hand, TNF alpha (30 ng.ml-1) caused an approximately 50% reduction
      in tension (29 +/- 2 mg vs 16 +/- 5 mg) in the skinned preparation (P < 0.05),
      but had no effect in the intact preparation. CONCLUSION: These results suggest
      that TNF alpha and SP act through different mechanisms. While SP requires an
      intact membrane, TNF alpha impairs function by a direct effect on the
      myofilaments.

PMID- 9597212
TI  - Anaesthesia affects outcome of sepsis in mice.
AB  - PURPOSE: To determine whether the survival curves and rates differ between a
      mutant strain of mice (C3H/HeJ: endotoxin-resistant) and an endotoxin-susceptible
      strain (C3H/HeN) when severe sepsis (caecal ligation and puncture: CLP) is
      performed with different anaesthetics (ketamine or varied exposure to halothane).
      METHODS: The CLP was performed under a randomly chosen anaesthetic method out of
      inhalation of halothane in oxygen (15 min, 2 hr, or 6 hr) (100, 120, and 103 mice
      respectively) or a single injection of ketamine im (127 mice) in paired fashion
      in eight-week-old male mice of each strain. The daily survival rates were
      compared between the two strains until the 10th day after CLP for each
      anaesthetic and among the four anaesthetic methods for each strain using multiple
      comparisons. RESULTS: The C3H/HeJ had delayed death relative to the C3H/HeN with
      every anaesthetic method except a two hours halothane (P < 0.01 at day 1 and day
      2-5 in halothane 15 min and 6 hr, P < 0.05 at day 4-6 in ketamine), however, the
      final survival rates for each method of anaesthesia were the same in the two
      strains. Regardless of the genetic susceptibility to endotoxin, short exposure to
      halothane resulted in the most rapid death compared with the other anaesthetic
      methods (P < 0.05), and two hours halothane showed the best survival. CONCLUSION:
      Endotoxin susceptibility affected the septic course for each anaesthetic method,
      and the anaesthetic methods influenced the survival from sepsis in both strains.

PMID- 9597213
TI  - Re-evaluation of i.m. ephedrine as prophylaxis against hypotension associated
      with spinal anaesthesia for Caesarean section.
AB  - PURPOSE: To assess the safety and efficacy of 37.5 mg ephedrine i.m. in
      preventing hypotension associated with spinal anaesthesia for Caesarean section.
      METHODS: In a double-blind randomised controlled study, 40 patients (20 in each
      group) were given either 37.5 mg ephedrine or placebo i.m. The following
      parameters were recorded: (i) blood pressure; (ii) heart rate; (iii) ephedrine
      i.v. supplementation; (iv) umbilical venous blood gases and neonatal Apgar
      scores. RESULTS: The incidence of hypertension in the study group was 30%
      compared with 20% for the control group (P:NS). There was no difference in mean
      highest blood pressure or mean highest heart rate between the groups. The
      incidence of hypotension was lower but not significantly lower in the study group
      (50%) than in the control group (80%) (P:NS). However, the incidence of delayed
      hypotension was only 10% in the study group patients compared with 50% in the
      control group patients (P < 0.05). CONCLUSION: Giving 37.5 mg ephedrine i.m.
      prior to spinal anaesthesia was not associated with reactive hypertension or
      tachycardia. Intramuscular ephedrine provided more sustained cardiovascular
      support than intravenous ephedrine.

PMID- 9597214
TI  - Decreased incidence of complications in parturients with the arrow (FlexTip Plus)
      epidural catheter.
AB  - PURPOSE: To compare the incidence of complications during placement of Arrow
      (FlexTip Plus) and Concord/Portex epidural catheters in parturients receiving
      continuous epidural analgesia. METHODS: Two hundred parturients requesting
      continuous epidural analgesia were prospectively and randomly assigned to receive
      either the Arrow (FlexTip Plus) or the Portex epidural catheter. The incidences
      of paresthesiae, inadvertent venous cannulation and inability to thread the
      catheter into the epidural space were recorded. RESULTS: A total of 222 attempts
      at epidural placement occurred in the parturients enrolled. The Arrow catheter
      displayed a lower incidence of paresthesiae (3/112 vs 39/110, P < 0.0001) and
      venous cannulation (0/112 vs 11/110, P = 0.0007) than did the Portex catheter.
      The Portex catheter demonstrated a tendency towards increased inability to be
      advanced into the epidural space (5/110 vs 0/112, P = 0.057) in comparison to the
      Arrow catheter. When a Portex catheter would not advance into the epidural space
      (n = 5), an Arrow catheter was threaded successfully in all five cases without
      the need to reposition the Tuohy needle. CONCLUSION: Compared with a less
      flexible catheter, the Arrow decreases the incidence of transient paresthesiae
      and inadvertent venous cannulation, while improving the ability to thread the
      catheter into the epidural space. Intravascular injection, transarachnoid
      migration, and the rare occurrence of epidural haematoma may be further reduced
      with the use of flexible, soft-tip catheters.

PMID- 9597215
TI  - Thoracic epidural block attenuates cardiovascular response to apnea in rabbits.
AB  - PURPOSE: Apnea is one of the potential complications during anaesthesia. If
      sympathetic nerve activity is blocked by epidural anaesthesia, circulatory
      responses to apnea might change. Our objective was to assess the potential
      modifying effects of epidural anaesthesia on the cardiovascular responses to
      apnea in the animals. METHODS: Twenty rabbits anaesthetised with pentobarbital
      (25 mg.kg-1 i.v., 8 mg.kg-1.hr-1) and pacuronium bromide (0.2 mg.kg-1.hr-1 i.v.)
      were randomly assigned to one of two groups: control (n = 10) and epidural (n =
      10). In the control group, 0.6 ml saline, and in the epidural group, 0.6 ml
      lidocaine 1% was injected into the epidural space respectively. After mechanical
      ventilation with FIO2 0.4, apnea was induced by disconnecting the anaesthetic
      circuit from the endotracheal tube, and mean arterial pressure (MAP), heart rate
      (HR), and time to cardiac arrest were measured. RESULTS: Before apnea MAP was
      lower in the epidural than in the control group (73 +/- 10 vs 91 +/- 10 mmHg, P <
      0.05). Heart rate was not different between groups (264 +/- 36 vs 266 +/- 24
      bpm). Mean arterial pressure increased in the control group after apnea, but not
      in the epidural group. The time to cardiac arrest was less in the epidural group
      than in the control group (420 +/- 67 vs 520 +/- 61 sec, P < 0.05). Heart rate
      decreased markedly after apnea in the control group whereas it decreased
      gradually in the epidural group. CONCLUSION: Thoracic epidural anaesthesia
      attenuated cardiovascular response to apnea and reduced the time to cardiac
      arrest.

PMID- 9597216
TI  - Anaesthesia for Caesarean section in Takayasu's disease.
AB  - PURPOSE: We present a case of Takayasu's Disease (Occlusive Thromboaortopathy
      OTAP) in which general anaesthesia was used for Caesarean section with processed
      encephalographic monitoring to detect cerebral ischaemia. CLINICAL FEATURES: The
      patient was a 33-year-old woman in whom OTAP had been the cause of
      cerebrovascular events. She had the typical pulseless upper body of OTAP and had
      documented severe bilateral carotid artery stenoses. Regional anaesthesia had
      failed in the past and she demanded general anaesthesia for Caesarean section.
      Processed electroencephalography was used to assist in monitoring for signs of
      cerebral ischaemia and the surgery was uncomplicated. CONCLUSION: The use of
      processed electroencephalographic monitoring allows some assessment of cerebral
      haemodynamics during general anaesthesia in patients who refuse regional
      techniques.

PMID- 9597217
TI  - Cricoid pressure.

PMID- 9597218
TI  - An unusual cause of elevated airway pressures.

PMID- 9597219
TI  - Decision-making in anaesthesia: an imbroglio of science, anecdotes and art?

PMID- 9597220
TI  - Fibreoptic laryngoscope blade.

PMID- 9597221
TI  - Clostridium difficile--associated diarrhea.

PMID- 9597222
TI  - Practice guidelines for infectious diseases: rationale for a work in progress.

PMID- 9597223
TI  - Practice guidelines for evaluating new fever in critically ill adult patients.
      Task Force of the Society of Critical Care Medicine and the Infectious Diseases
      Society of America.
AB  - OBJECTIVE: The development of practice guidelines for evaluating adult patients
      who develop new fever in the intensive care unit (ICU) for the purpose of guiding
      clinical practice. PARTICIPANTS: A task force of 13 experts in disciplines
      related to critical care medicine, infectious diseases, and surgery was convened
      from the membership of the Society of Critical Care Medicine and the Infectious
      Disease Society of America. EVIDENCE: The task force members provided personal
      experience and determined the published literature (articles retrieved with use
      of MEDLINE or textbooks) from which consensus would be sought. The published
      literature was reviewed and classified into one of four categories, according to
      study design and scientific value. CONSENSUS PROCESS: The task force met several
      times in person and twice monthly by teleconference over a 1-year period to
      identify the pertinent literature and arrive at consensus recommendations.
      Consideration was given to the relationship between the weight of scientific
      evidence and the experts' opinions. Draft documents were composed and debated by
      the task force until consensus was reached by nominal group process. CONCLUSIONS:
      The panel concluded that because fever can have many infectious and noninfectious
      etiologies, a new fever in an adult patient in the ICU should trigger a careful
      clinical assessment rather than automatic orders for laboratory and radiological
      tests. A cost-conscious approach to obtaining diagnostic studies should be
      undertaken if they are indicated after a clinical evaluation. The goal of such an
      approach is to determine, in a directed manner, whether infection is present so
      that additional testing can be avoided and therapeutic options can be identified.

PMID- 9597224
TI  - Fellowship training in infectious diseases: a report from the regional and
      national meetings of infectious diseases division chiefs and program directors.
AB  - During the 2-year period April 1995 to April 1997, six regional meetings and one
      national meeting of division chiefs and program directors of adult infectious
      diseases programs in the United States were held to review fellowship training.
      Herein, we report data on job availability and job selection for recently
      graduated fellows. We summarize discussions on decreasing the number of fellows
      in training, and we outline suggested components of a core clinical curriculum
      and of three training tracks--clinician track, clinical investigator track, and
      basic investigator track.

PMID- 9597225
TI  - Epidemiology of severe hospital-acquired infections in patients with liver
      cirrhosis: effect of long-term administration of norfloxacin.
AB  - We performed a 5-year retrospective study to evaluate the effect of long-term
      administration of norfloxacin on the epidemiology of severe hospital-acquired
      infections in patients with advanced cirrhosis. Sixty-seven episodes of
      spontaneous bacterial peritonitis and 60 episodes of bacteremia occurred in,
      respectively, 46 patients (group 1a) and 52 patients (group 1b) who did not
      receive norfloxacin, while 23 and 17 episodes occurred in 21 patients (group 2a)
      and 17 patients (group 2b) during or within 10 days after long-term
      administration of norfloxacin. Enterobacteriaceae were more prevalent in groups
      1a and 1b than in the other two groups (P < .001 and P < .01, respectively);
      conversely, staphylococci were more prevalent in groups 2a and 2b (P < .001 and P
      < .05, respectively). The rate of staphylococcal resistance to methicillin was
      53.6% in groups 1a and 1b and 77.3% in groups 2a and 2b. We conclude that long
      term norfloxacin administration to cirrhotic patients reduces the risk of gram
      negative infections but increases the risk of severe hospital-acquired
      staphylococcal infections and of high-level resistance to antibiotics.

PMID- 9597226
TI  - Photo quiz I. Hereditary hemorrhagic telangiectasia, pulmonary arteriovenous
      malformations, and brain abscess.

PMID- 9597227
TI  - The level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid
      as a marker of HIV encephalitis.
AB  - We prospectively evaluated the level of human immunodeficiency virus (HIV) type 1
      RNA in cerebrospinal fluid (CSF) as a marker of HIV encephalitis. Fifty-two HIV-1
      infected patients (41 males and 11 females; mean age, 39 years) were tested for
      the presence of HIV-1 RNA in plasma and CSF. Samples of CSF were obtained by
      lumbar puncture to evaluate cognitive deficits, seizures, or fever among these
      patients. HIV encephalitis was diagnosed in 11 patients (21%), other CNS diseases
      were diagnosed in 12 (23%), and fever without CNS disease was diagnosed in 29
      (56%). HIV-1 RNA was detectable in 92% of the plasma specimens and 75% of the CSF
      specimens. No significant difference was observed in CSF levels of HIV-1 RNA
      between patients with or without HIV encephalitis. CSF levels of HIV-1 RNA
      correlated with plasma levels of HIV-1 RNA (Spearman's rank correlation, +0.31; P
      = .02) and CSF white blood cell counts (Spearman's rank correlation, +0.4; P <
      .01). The absence of any significant difference between patients with or without
      HIV encephalitis suggests that the CSF HIV-1 RNA level is not a good marker for
      the diagnosis of HIV encephalitis.

PMID- 9597228
TI  - Does the human immunodeficiency virus (HIV) RNA concentration in cerebrospinal
      fluid help clinicians diagnose or understand HIV-induced neurological disease?

PMID- 9597229
TI  - High incidence of active cytomegalovirus infection among septic patients.
AB  - Cytomegalovirus (CMV) infection is an important cause of disease in
      immunocompromised patients. In a prospective longitudinal study of 34 septic
      patients, the incidence of active CMV infection was examined. Eleven of 34
      patients (32.4%) had active CMV infection, diagnosed by immunocytochemical
      staining of CMV pp65 antigen in blood leukocytes and/or detection of CMV DNA by
      PCR. Positive results for CMV infection were obtained in a median of 4 days (by
      PCR) or 11 days (by staining of pp65 antigen) after onset of sepsis. Twenty
      patients for whom more than one sample was examined were selected for further
      analysis. Among the patients with active CMV infection (nine of 20) there was a
      trend toward higher median values of tumor necrosis factor alpha, interleukin-1
      beta, alanine aminotransferase, and aspartate aminotransferase in plasma, in
      comparison with the values for patients without CMV infection. Sepsis in patients
      with CMV infection may affect outcome of the disease.

PMID- 9597230
TI  - Cytomegalovirus infection in patients with bacterial sepsis.

PMID- 9597231
TI  - Photo quiz II. Luminal anisakidosis due to Pseudoterranova decipiens.

PMID- 9597232
TI  - Emergence of Candida parapsilosis as the predominant species causing candidemia
      in children.
AB  - An increase in the rate of isolation of Candida parapsilosis, relative to other
      Candida species, in our children's hospital led us to analyze the clinical and
      epidemiological variables associated with candidemia. We sought to determine if
      these variables are different for patients infected with C. parapsilosis. All
      episodes of candidemia occurring over a 7-year period were analyzed
      retrospectively. Of 81 episodes in 80 patients, 35 (43%) were in neonates, and 46
      (57%) were in nonneonates. C. parapsilosis was isolated in 40 episodes (49%). C.
      parapsilosis was significantly more likely than non-C. parapsilosis species to be
      associated with prematurity (P = .001), presence of a central venous catheter (P
      = .002), and use of total parenteral nutrition (P = .03). C. parapsilosis has
      emerged as the predominant species in our children's hospital. The mortality rate
      associated with candidemia in children is lower than previously reported and may
      be associated with the high rate of isolation of C. parapsilosis.

PMID- 9597233
TI  - New aspects of malaria imported from Ethiopia.
AB  - We describe a high incidence of Plasmodium vivax malaria among travelers
      returning from Ethiopia, who all took the recommended prophylaxis. Three groups
      of 7-11 nonimmune travelers received mefloquine (250 mg weekly), beginning 1-2
      weeks prior to departure and continuing for 4 weeks after their return. A fourth
      group mistakenly took inadequate prophylaxis and is presented for comparison.
      Vivax malaria occurred at a rate of up to 50% in the first three groups; nearly
      all patients became ill 3 months after exposure. In the fourth group, primary
      attacks of both falciparum and vivax malaria occurred within 1 month of return,
      at an incidence of 50%. The use of mefloquine prevented Plasmodium falciparum
      infection, but a very high rate of relapses of P. vivax infection occurred. The
      complexity of prophylaxis for malaria in an area with a high rate of both P.
      falciparum and P. vivax infections and the urgent need for effective causal
      prophylaxis are discussed.

PMID- 9597234
TI  - Invasive pulmonary aspergillosis due to Aspergillus terreus: 12-year experience
      and review of the literature.
AB  - A 12-year retrospective analysis was done to identify and evaluate in detail
      cases of invasive pulmonary aspergillosis (IPA) caused by Aspergillus terreus. We
      identified 13 A. terreus infections among 133 total cases of confirmed invasive
      aspergillosis; 11 were IPA and 2 were primary peritoneal infections. Of the 11
      patients with IPA, 7 developed neutropenia during hospitalization, and the
      remaining four were receiving immunosuppressive agents. Ten patients with IPA
      died; one liver transplantation patient without neutropenia survived after
      treatment with amphotericin B, itraconazole, and a pulmonary lobectomy. Six
      patients developed disseminated disease, with the heart the most common
      extrapulmonary site identified (four patients). These cases demonstrate that IPA
      caused by A. terreus rapidly progresses in immunocompromised patients receiving
      amphotericin B and illustrate the need for sensitive diagnostic tests and more
      effective antifungal agents.

PMID- 9597235
TI  - Impact of previous aspergillosis on the outcome of bone marrow transplantation.
AB  - A retrospective analysis of 48 patients with documented or probable invasive
      aspergillosis (IA) prior to bone marrow transplantation (BMT) was conducted in 16
      centers. Treatment of primary IA was medical in all 48 patients and surgical in
      20; clinicoradiological resolution of IA occurred in 30 of 48 patients.
      Pretransplantation risk factors for relapse IA, total mortality, and IA-related
      mortality were analyzed by multivariate logistic regression with the following
      dichotomous risk factors: surgery as part of the initial treatment, resolution of
      IA by the time of BMT, donor type, conditioning regiment, total-body irradiation,
      T cell depletion, immunosuppressive therapy, type of antifungal prophylaxis, and
      growth factor prophylaxis. Conditioning with busulfan/cyclophosphamide was
      associated with a beneficial outcome for total survival and reduced IA-related
      mortality. Posttransplantation risk factors such as the development of graft-vs.
      host disease (GVHD), therapy for GVHD, and the duration of neutropenia did not
      have a significant effect on relapse IA, IA-related mortality, or total
      mortality. The overall incidence of relapse IA was lower than expected (33% [16
      of 48 patients]), but the mortality rate among relapsed patients was 88% (14 of
      16). Patients receiving prophylaxis with absorbable or intravenous antifungals
      had less relapses of IA than did those not receiving prophylaxis (12 of 41 vs.
      four of seven, respectively). This finding reflects the need for better
      prophylaxis and new antifungal treatments for patients undergoing BMT who have a
      history of IA.

PMID- 9597236
TI  - Tritherapy for human immunodeficiency virus infection does not modify replication
      of hepatitis C virus in coinfected subjects.
AB  - Triple antiretroviral therapy combining reverse transcriptase and protease
      inhibitors modifies the prognosis for human immunodeficiency virus (HIV)
      infection, with dramatic improvement in immune status. In an attempt to evaluate
      the impact of anti-HIV triple combination therapy on the course of hepatitis C
      virus (HCV)-related chronic hepatitis and on HCV replication, we studied the
      biological and virological characteristics of 22 HCV/HIV-coinfected patients who
      were given triple combination therapy. In comparison with baseline values, there
      was (1) a significant increase in the CD4 and CD8 cell counts and a decrease in
      the HIV RNA load and (2) no significant variation in aminotransferase activities
      or the HCV RNA load at 3, 6, or 9 months of tritherapy. Antiretroviral tritherapy
      seems to modify neither the biological activity of HCV-related chronic hepatitis
      nor the HCV load, despite immune restoration. Hepatic histopathologic analysis is
      warranted to assess the impact of immune restoration on liver lesions.

PMID- 9597237
TI  - Amphotericin B and itraconazole for treatment of disseminated Penicillium
      marneffei infection in human immunodeficiency virus-infected patients.
AB  - Disseminated infection with Penicillium marneffei is common in patients infected
      with human immunodeficiency virus (HIV) in Southeast Asia. Treatment with
      amphotericin B alone is effective but requires a prolonged hospital stay. We
      conducted an open-label nonrandomized study to evaluate the efficacy and safety
      of treatment with amphotericin B at a dosage of 0.6 mg/(kg.d) intraveneously for
      2 weeks, followed by a 400-mg/d dosage of oral itraconazole for 10 weeks. Of the
      74 HIV-infected patients we studied who had disseminated P. marneffei infection,
      diagnosed by positive fungal culture and clinical evidence of infection, 72
      (97.3%) responded to the treatment. There were no serious adverse drug effects.
      It was concluded that the regimen was effective and safe for treatment of
      disseminated P. marneffei infection in HIV-infected patients.

PMID- 9597238
TI  - Clinical presentation and analysis of risk factors for infectious complications
      of implantable cardioverter-defibrillator implantations at a university medical
      center.
AB  - The objective of this report is to describe the characteristics of patients who
      develop infections associated with implantable cardioverter-defibrillators (ICDs)
      implanted with sternotomy and thoracotomy approaches. A retrospective chart
      review identified all patients who underwent ICD implantation at a university
      medical center from November 1982 through February 1990. Several patient and
      procedural variables were compared between infected patients and noninfected
      patients. One hundred fifty-seven patients underwent 202 ICD generator
      implantations (45 generator changes), and nine of these patients developed
      infection (4.5% per implantation and 5.7% per patient). Of the patient variables
      analyzed, a significant correlation (P < .0001) was made only with a diagnosis of
      diabetes mellitus: 36% of diabetics versus 3.9% of nondiabetics were infected.
      The only patient- or procedure-specific variable that was found to correlate with
      the development of infection was the presence of diabetes mellitus.

PMID- 9597239
TI  - Pneumococcal vaccination in the United States and 20 other developed countries,
      1981-1996.
AB  - This survey describes patterns of pneumococcal polysaccharide vaccine use,
      vaccine registration, vaccination recommendations, and reimbursement for
      vaccination in the United States and 20 other developed countries during the
      period 1981 through 1996. The United States was the only country to use
      appreciable amounts of the vaccine throughout the study period. Annual vaccine
      use was staple from 1982 through 1990 but then increased sharply. In the 20 other
      countries, very little pneumococcal vaccine was used until the 1990s, when new
      registrations and/or national recommendations were followed by dramatic increases
      in vaccine use in Iceland (1991), the United Kingdom (1994), Sweden (1995), and
      Norway, Belgium, and the province of Ontario in Canada (1996). In 1996,
      pneumococcal vaccine was still not licensed in three and not recommended in four
      of the 21 countries. Of the seven countries that used the most pneumococcal
      vaccine, public reimbursement for vaccination was provided in the United States,
      Canada, and the United Kingdom but not in Iceland, Sweden, Norway, or Belgium.

PMID- 9597240
TI  - Prevention of pneumococcal disease--a new romance begins.

PMID- 9597241
TI  - Vancomycin-resistant and vancomycin-susceptible enterococcal bacteremia:
      comparison of clinical features and outcomes.
AB  - Vancomycin-resistant Enterococcus (VRE) is a major nosocomial pathogen. We
      collected clinical and laboratory data on 93 hospitalized adults with VRE
      bacteremia and 101 adults with vancomycin-susceptible enterococcal (VSE)
      bacteremia. Risk factors for VRE bacteremia included central venous
      catheterization, hyperalimentation, and prolonged hospitalization prior to the
      initial blood culture. VRE-infected patients were less likely to have undergone
      recent surgery or have polymicrobial bacteremia, suggesting a pathogenesis
      distinct from traditional VSE bacteremia. Prior exposure to metronidazole was the
      only significant pharmacologic risk factor for VRE bacteremia. Animal studies
      suggest metronidazole potentiates enterococcal overgrowth in the gastrointestinal
      tract and translocation into the bloodstream. An increasing APACHE II score was
      the major risk factor for death in a multivariate analysis, with VRE status being
      of only borderline significance.

PMID- 9597242
TI  - Candidemia: a nosocomial complication in adults with late-stage AIDS.
AB  - We retrospectively analyzed 13 episodes of candidemia observed between July 1990
      and July 1995 in human immunodeficiency virus (HIV)-infected adults. Candidemia
      was nosocomially acquired by 11 patients, among whom nine had a central venous
      catheter (CVC). Twelve cases were of stage C2/C3 according to the 1993
      classification of the Centers for Disease Control and Prevention. The median CD4+
      cell count was 10/mm3 (range, 3-400/mm3). Causative species were Candida albicans
      in nine episodes and Candida glabrata and Candida krusei in two episodes each.
      Eleven episodes occurred in 11 patients who had previously received fluconazole
      (mean total dose, 7.4 g), including the four episodes caused by non-albicans
      species. Outcome did not differ according to the administered antifungal therapy.
      CVCs were removed from seven patients (78%). The overall mortality was 38%.
      Candidemia is a potentially lethal nosocomial complication during late-stage AIDS
      and can be due to C. albicans and non-albicans strains.

PMID- 9597243
TI  - Human IgE, IgG subclass, and IgM responses to worm and egg antigens in
      schistosomiasis haematobium: a 12-month study of reinfection in Cameroonian
      children.
AB  - Levels of IgE, IgM, and IgG subclasses against Schistosoma haematobium adult worm
      antigen (AWA) and soluble egg antigen (SEA) in a cohort of 148 S. haematobium
      infected schoolchildren were determined before and up to 12 months after
      chemotherapy. Infection intensities were determined as concentrations of
      circulating anodic antigen (CAA) in serum. One month posttreatment, the antibody
      levels of all isotypes against AWA were increased, but 1 year after treatment
      they returned to pretreatment levels. CAA concentrations were positively
      associated with levels of IgG4 against AWA and SEA but not with levels of IgE.
      Age correlated negatively with CAA concentrations and positively with levels of
      IgE to AWA. The balance of anti-AWA IgG4 and IgE was significantly correlated to
      the CAA concentration, in particular in the older age group (11-13 years). This
      may suggest that protective immune mechanisms in S. haematobium infections become
      effective around the age of 12 years.

PMID- 9597244
TI  - Evaluation of an intensive intermittent-induction regimen and duration of short
      course treatment for human immunodeficiency virus-related pulmonary tuberculosis.
      Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS
      Clinical Trials Group (ACTG).
AB  - This study examined whether adding levofloxacin to a standard four-drug regimen
      improved the 8-week culture response and compared effectiveness of 9 versus 6
      months of intermittent therapy for human immunodeficiency virus-related
      pansusceptible pulmonary tuberculosis. Patients were randomized to receive either
      four or five drugs, the fifth being levofloxacin. Patients who completed
      induction therapy were randomized to complete 9 versus 6 months of intermittent
      therapy with isoniazid and rifampin. In the randomized induction phase, 97.3% of
      patients in the four-drug group and 95.8% in the five-drug group had sputum
      culture conversion at 8 weeks (P = 1.00). In the continuation phase, one patient
      (2%) assigned to 9 months and two patients (3.9%) assigned to 6 months of therapy
      had treatment failure/relapse (P = 1.00). In conclusion, this study showed that
      levofloxacin added no benefit to a highly effective, largely intermittent, four
      drug induction regimen. Both 9 and 6 months of intermittent therapy were
      associated with low treatment failure/relapse rates.

PMID- 9597245
TI  - Complications and sequelae of meningococcal disease in Quebec, Canada, 1990-1994.
AB  - To study complications and sequelae of serogroup B and C meningococcal disease, a
      retrospective survey examined the outcome of all culture-proven cases reported in
      the province of Quebec, Canada, from January 1990 through December 1994
      (serogroup B, 167 cases; serogroup C, 304 cases). Data were collected from
      medical files, postal questionnaires, and telephone interviews. Age groups having
      the most cases were the 10-19-year age group for serogroup C and the < 1-year age
      group for serogroup B. Fatality rates were 7% for serogroup B and 14% for
      serogroup C disease. Only 3% of survivors of serogroup B disease had physical
      sequelae, compared with 15% of survivors of serogroup C disease (skin scars, 12%;
      amputations, 5%; hearing loss, 2%; renal problems, 1%; and other sequelae, 4%).
      These results confirm the gravity of disease caused by serogroup C, serotype 2a
      Neisseria meningitidis and justify liberal use of vaccination for outbreak
      control.

PMID- 9597246
TI  - Native valve infective endocarditis in elderly and younger adult patients:
      comparison of clinical features and outcomes with use of the Duke criteria and
      the Duke Endocarditis Database.
AB  - The effect of age on the presentation and outcome of infective endocarditis (IE)
      is unclear. Many of the available data are based on analyses of mixed populations
      of patients including intravenous drug users or those with prosthetic valve
      endocarditis or native valve IE. We used the Duke criteria to compare the
      characteristics of 44 episodes of definite native valve IE in elderly patients (>
      64 years old) with the characteristics of 64 similarly defined episodes of native
      valve IE in younger, nonintravenous-drug-using adult patients (> 29 years and <
      60 years old). Our data suggest that the clinical presentation, characteristics,
      and outcome of native valve IE are similar for elderly patients and younger adult
      patients, although elderly patients were hospitalized an average of 12 days
      longer. Although we found that the occurrence of renal failure and cerebral
      embolism during an episode of IE was associated with higher rates of death (odds
      ratios, 4.8 and 4.0, respectively), age was not a significant contributor to
      mortality.

PMID- 9597247
TI  - In vitro antibiotic synergy against Flavobacterium meningosepticum: implications
      for therapeutic options.
AB  - Flavobacterium meningosepticum is an unusual, highly resistant, gram-negative
      bacillus that is associated with neonatal meningitis and nursery outbreaks of
      meningitis. The optimal therapy for this infection is not known. We successfully
      treated three neonates with intravenous vancomycin and rifampin. We determined
      the in vitro activity of meropenem, ciprofloxacin, vancomycin, linezolid (PNU
      100766), and rifampin, alone and in combination, against four isolates of F.
      meningosepticum from neonates with sepsis and meningitis. MICs were determined by
      tube dilution, and fractional inhibitory concentrations were calculated with use
      of the checkerboard microtiter dilution technique. Synergy was observed between
      rifampin and vancomycin against three isolates, while combinations of vancomycin,
      ciprofloxacin, and linezolid showed an additive effect against all isolates.
      These results support the clinical evidence that the combination of vancomycin
      and rifampin is an appropriate regimen for neonatal meningitis due to F.
      meningosepticum. The combination of meropenem and vancomycin was antagonistic.
      The clinical efficacy of combinations including ciprofloxacin, newer quinolones,
      or linezolid for treating F. meningosepticum meningitis deserves further study.

PMID- 9597248
TI  - Problems with antimicrobial resistance in gram-positive cocci.
AB  - The development of antimicrobial resistance has almost invariably accompanied the
      therapeutic use of antimicrobial agents. Newer antimicrobials have succeeded
      partly but not entirely in overcoming the problem of resistance. Antimicrobial
      resistance in gram-positive cocci has achieved its greatest prominence in the
      past 15 years. There has been a steady erosion of antimicrobial activity against
      gram-positive cocci. The presentations in this symposium dealt with some of the
      important problems of antimicrobial resistance in gram-positive cocci, including
      methicillin resistance and multidrug resistance in staphylococci, penicillin
      resistance in pneumococci, and vancomycin resistance in enterococci. A related
      problem that warrants attention is the potential for explosive development of
      macrolide resistance in gram-positive cocci. This potential is particularly
      pertinent because the popularity of a number of new macrolides has led to a
      striking increase in their use. This occurrence will almost certainly be
      accompanied by a generalized increase in resistance in gram-positive cocci.

PMID- 9597249
TI  - Staphylococcus aureus: a well-armed pathogen.
AB  - Staphylococcus aureus is a virulent pathogen that is currently the most common
      cause of infections in hospitalized patients. S. aureus infection can involve any
      organ system. The success of S. aureus as a pathogen and its ability to cause
      such a wide range of infections are the result of its extensive virulence
      factors. The increase in the resistance of this virulent pathogen to
      antibacterial agents, coupled with its increasing prevalence as a nosocomial
      pathogen, is of major concern. The core resistance phenotype that seems to be
      most associated with the persistence of S. aureus in the hospital is methicillin
      resistance. Methicillin resistance in nosocomial S. aureus isolates has been
      increasing dramatically in United States hospitals and is also associated with
      resistance to other useful antistaphylococcal compounds. Possible ways to
      decrease the incidence of nosocomial S. aureus infections include instituting
      more effective infection control, decreasing nasal colonization, developing
      vaccines, and developing new or improved antimicrobials.

PMID- 9597250
TI  - Staphylococcus epidermidis: emerging resistance and need for alternative agents.
AB  - Previously, Staphylococcus epidermidis and other coagulase-negative staphylococci
      isolated from the blood of hospitalized patients were often considered
      contaminants. Now, coagulase-negative staphylococci are among the leading causes
      of nosocomial blood infections. Multidrug resistance could predict a true
      nosocomial infection rather than a blood culture contaminant. Recent studies
      indicated the emergence of resistance to the quinolones, particularly to
      ciprofloxacin. Tolerance and occasional resistance to vancomycin have been
      reported recently. In addition, several reports indicated that vancomycin and
      other glycopeptide antibiotics lose their effectiveness against S. epidermidis
      organisms embedded in the biofilm environment on the surface of medical devices.
      Alternative agents have been proposed in the prevention and treatment of device
      related and glycopeptide-tolerant S. epidermidis infections. These agents include
      minocycline, rifampin, and, more recently, quinupristin/dalfopristin and the
      oxazolidinones.

PMID- 9597251
TI  - Drug-resistant Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae remains a major cause of infection in both children and
      adults, annually resulting in significant morbidity and mortality. The past two
      decades have seen an alarming worldwide increase in the incidence of drug
      resistant S. pneumoniae (DRSP). DRSP is now common throughout the United States,
      and physicians are questioning how best to approach this epidemic. With the
      introduction of a number of newer antimicrobial agents, the potential for
      improved preventive measures, and a better understanding of DRSP, the approach to
      the management of DRSP infections may change greatly in the next few years. In
      this article we will review the development of DRSP, identify populations at
      increased risk of exposure to DRSP, address what approaches might be used to
      limit its spread, and suggest initial empirical therapy when treating patients
      with pneumonia due to DRSP.

PMID- 9597252
TI  - Vancomycin-resistant enterococci.
AB  - Enterococci, a part of normal gut flora, are not particularly pathogenic
      organisms in humans. For example, they do not cause respiratory tract infections.
      The most frequent enterococcal infections are urinary tract infections. Despite
      their lack of pathogenicity, enterococci have emerged as significant nosocomial
      pathogens in the United States and elsewhere. Enterococci are formidable
      pathogens because of their resistance to antimicrobial agents. Enterococci are
      intrinsically resistant to beta-lactam agents and aminoglycosides and were the
      first bacteria to acquire vancomycin resistance. Infection control measures have
      been far from effective at preventing the dissemination of vancomycin-resistant
      enterococci in the hospital. Therapy for infections due to vancomycin-resistant
      enterococci presents real challenges. Most isolates remain susceptible to
      nitrofurantoin, but this agent is useful only for urinary tract infections. The
      greatest threat posed by vancomycin-resistant enterococci is the potential to
      transfer their resistance genes to more pathogenic gram-positive bacteria, which
      could produce truly frightening pathogens.

PMID- 9597253
TI  - Epidemiology, appropriateness, and cost of vancomycin use.
AB  - Pharmaceutical costs, which approach $40 billion annually, account for about 8%
      of health care costs. Prescription drugs represent 5% to 20% of the total
      hospital budget, and antimicrobials account for 20% to 50% of hospital
      pharmaceutical costs. At one university hospital, the percentage of patients
      receiving antimicrobials increased from 31.8% in 1988 to 53.1% in 1994. Receipt
      of vancomycin has been associated with the emergence of resistant enterococci and
      has resulted in Centers for Disease Control and Prevention (CDC) recommendations
      for its use. Studies show that vancomycin use is increasing, that dosing is often
      inappropriate, that certain populations (such as oncology, neurosurgery, and
      cardiovascular surgery patients) are more likely to receive vancomycin, and that
      often use is not consistent with CDC recommendations. Few studies have assessed
      the cost of vancomycin use; those that have show that it is costly. Further
      studies of vancomycin use are needed, so that use can be improved through focused
      educational programs.

PMID- 9597254
TI  - Genesis of methicillin-resistant Staphylococcus aureus (MRSA), how treatment of
      MRSA infections has selected for vancomycin-resistant Enterococcus faecium, and
      the importance of antibiotic management and infection control.
AB  - We extensively studied the epidemiology and time course of endemic methicillin
      resistant Staphylococcus aureus (MRSA) in the Millard Fillmore Hospital, a 600
      bed teaching hospital in Buffalo. The changeover from methicillin-susceptible S.
      aureus to MRSA begins on the first hospital day, when patients are given
      cefazolin as presurgical prophylaxis. Under selective antibiotic pressure,
      colonizing flora change within 24 to 48 hours. For patients remaining
      hospitalized, subsequent courses of third-generation cephalosporins further
      select and amplify the colonizing MRSA population. Therefore, managing antibiotic
      selective pressure might be essential. Other strategies include attention to
      dosing, so that serum concentrations of drug exceed the minimum inhibitory
      concentration, and antibiotic cycling. Although there are some promising new
      antibiotics on the horizon, it is necessary to deal with many resistance patterns
      by using the combined strategies of infection control and antibiotic management.

PMID- 9597255
TI  - Hepatic penicilliosis in patients without skin lesions.
AB  - Penicillium marneffei is a common cause of opportunistic fungal infection in
      patients with AIDS in Thailand. The diagnosis of penicilliosis is easily made
      when typical skin lesions appear but is frequently missed in their absence. We
      therefore attempted to identify noncutaneous indicators of P. marneffei infection
      in order to provide early curative treatment. We recognized a characteristic
      syndrome in six AIDS patients with penicilliosis involving primarily the liver
      but not the skin who presented with fever of short duration, hepatomegaly, and
      markedly elevated serum alkaline phosphatase levels. The diagnosis was confirmed
      by demonstrating the causative organism in the liver or in the blood. Increased
      awareness of hepatic penicilliosis and more-rapid diagnostic methods are needed
      to reduce the high mortality rate associated with this syndrome. P. marneffei is
      predominantly an Asian pathogen, but as a result of international travel, the
      need for increased awareness of penicilliosis is worldwide.

PMID- 9597256
TI  - Relative bradycardia and lymphopenia in patients with babesiosis.
AB  - The medical records of 17 patients with babesiosis were reviewed. Nine of 17
      patients (52.9%) presented with fever (temperature, > 101 degrees F), and 8 of
      the 9 patients (88.9%) had relative bradycardia. Four of the nine patients
      (44.4%) had morning temperature spikes during initial hospitalization. As
      revealed by laboratory analysis, 13 of 17 patients (76.5%) with babesiosis had
      lymphopenia, and 5 of 17 patients (29.4%) had rouleaux formation in their
      peripheral blood smears. These newly described clinical and laboratory findings
      represent additional clinical and laboratory features that may be used as
      diagnostic clues in the differential diagnosis of babesiosis.

PMID- 9597257
TI  - Hepatocellular carcinoma presenting as pyogenic liver abscess: characteristics,
      diagnosis, and management.
AB  - We performed a 17-year retrospective analysis of 10 cases of hepatocellular
      carcinoma presenting as pyogenic liver abscess. Spontaneous tumor necrosis and
      biliary obstruction caused by tumor thrombi, superimposed with bacterial
      infection, were the two major pathogeneses. Exact diagnosis of the underlying
      hepatocellular carcinoma was made for five of the 10 patients before management
      was attempted. Main clinical manifestations included fever, chills, right-upper
      quadrant pain, malaise, anorexia, jaundice, and hepatomegaly. Characteristics
      such as middle age and male sex, seropositivity for hepatitis B and/or hepatitis
      C, chronic liver disease, unexplained anemia, marked weight loss, and a severely
      inversed albumin/globulin ratio raise suspicions about the underlying
      hepatocellular carcinoma. Management strategies included percutaneous drainage (n
      = 3), surgical drainage (n = 4), and hepatectomy (n = 3) in addition to
      administration of parenteral antibiotics in all cases. The prognosis was dismal,
      with a mean survival of 3.5 months (range, 8 days to 6 months).

PMID- 9597258
TI  - Prevalence of intestinal encephalitozoonosis in Mexico.
AB  - Infections with Encephalitozoon (phylum Microspora) protozoa in immunodeficient
      patients have emerged worldwide. The prevalence of infections due to
      Encephalitozoon species in nonclinical populations remains unclear. We conducted
      a cross-sectional survey of two rural highland villages in Mexico by using
      monoclonal antibody 3B6 to Encephalitozoon in immunofluorescence to assess the
      prevalence of Encephalitozoon spores in human stools. We found that 20 (7.84%) of
      the 255 subjects were positive and that 15 (21.4%) of the 70 households had at
      least one member who was positive. These results suggest that Encephalitozoon
      species, most likely Encephalitozoon intestinalis, may be commonly present in
      community settings.

PMID- 9597259
TI  - Septic siblings with pneumonia due to penicillin-resistant Streptococcus
      pneumoniae.

PMID- 9597260
TI  - Paradoxical local response to therapy for Mycobacterium avium complex infection
      in four patients with AIDS.

PMID- 9597261
TI  - Abatement of cutaneous Kaposi's sarcoma associated with cidofovir treatment.

PMID- 9597262
TI  - Successful treatment of infection due to Mycoplasma hominis with streptogramins
      in a renal transplant patient: case report and review.

PMID- 9597263
TI  - Furunculosis associated with repeated courses of omeprazole therapy.

PMID- 9597264
TI  - Pseudo-outbreak of tuberculosis infection due to improper skin-test reading.

PMID- 9597265
TI  - Two rules in medicine.

PMID- 9597266
TI  - Anaphylaxis upon switching lipid-containing amphotericin B formulations.

PMID- 9597267
TI  - Cure of metronidazole- and tinidazole-resistant trichomoniasis with use of high
      dose oral and intravaginal tinidazole.

PMID- 9597268
TI  - Staphylococcus epidermidis endocarditis treated with RP 59500
      (quinapristin/dalfopristin).

PMID- 9597269
TI  - Acute epiglottitis caused by methicillin-resistant Staphylococcus aureus in
      adults.

PMID- 9597270
TI  - Colonic polyps and disseminated infection associated with Rhodococcus equi in a
      patient with AIDS.

PMID- 9597271
TI  - Treatment of thrush with itraconazole solution: evidence for topical effect.

PMID- 9597272
TI  - Group B streptococcal meningoencephalitis after conization in a nonpregnant
      woman.

PMID- 9597273
TI  - Boerhaave's syndrome due to herpes simplex virus type 1 esophagitis in a patient
      with AIDS.

PMID- 9597274
TI  - Polymicrobial endocarditis with Haemophilus parainfluenzae in an intravenous drug
      user whose transesophageal echocardiogram appeared normal.

PMID- 9597276
TI  - Clostridium difficile colitis: a possible cause of unexplained elevation of serum
      alkaline phosphatase levels in patients with AIDS.

PMID- 9597275
TI  - Lactobacillus bacteremia in febrile neutropenic patients in a cancer hospital.

PMID- 9597277
TI  - 'External' Mustarde suture technique in otoplasty.
AB  - Although preferences may vary in otoplasty surgery the antihelical fold is
      frequently created using Mustarde sutures. Technically it is important to insert
      the needle through the cartilage at right angles and to take a good 'bite' of
      cartilage. These technical objectives are easily achieved by bringing the needle
      out through the skin and then placing it in a redirected course through exactly
      the same needle hole from which it exited the skin. The technique is simple and
      easily learnt.

PMID- 9597278
TI  - Does age or sex affect pharyngeal swallowing?
AB  - The influence of age and gender on the pharyngeal pressure wave during swallowing
      was investigated in 73 healthy volunteers using a four-sensor manometry probe.
      The distal sensor was placed within the upper oesophageal sphincter (UOS) and
      three proximal sensors were located in the pharynx 2, 4 and 6 cm above the UOS.
      Twenty-nine variables describing the amplitude and timing of the swallow
      waveforms for a 5 ml water bolus were recorded from the pharynx and the UOS.
      Analysis of the results indicated that aging was associated with slowing of the
      swallow response in the pharynx, impaired opening of the UOS and a marked
      reduction in resting UOS tone.

PMID- 9597279
TI  - Mucosal melanoma of the head and neck.
AB  - Two hundred and fifty-nine patients with mucosal melanoma of the head and neck
      were reviewed. The data of these patients were obtained from the records of the
      Department of Head and Neck Oncology at the University of Liverpool and from the
      Merseyside and Cheshire Cancer Registry. Survival curves were constructed using
      the life table method and differences were investigated by the Log Rank Test.
      Prognostic factors were further analysed by Cox's proportional hazards model.
      Melanomas of the nasal cavities and sinuses accounted for 69%; 22% occurred in
      the oral cavity and 9% in the pharynx, larynx and upper oesophagus. In 49%
      treatment was by wide local resection and in 8% by irradiation. Thirty-six per
      cent had combined modalities of treatment. Primary site recurrence occurred in
      52% and 36% developed nodal recurrence. The tumour specific survival at 5 years
      was 45% at 10 years 28%, at 20 years 17% and closely resembled the observed
      survival. Young male patients tended to have a favourable prognosis as did those
      treated surgically. Radiotherapy on its own was ineffective. Amelanotic melanoma
      had a particularly poor survival. Whereas site had no effect on survival. The
      study confirms the poor prognosis of mucosal melanoma of the head and neck. Young
      patients should be offered radical surgical treatment combined with radical
      radiotherapy if feasible as this offers the best chance of cure.

PMID- 9597280
TI  - A clinical evaluation of head impulse testing.
AB  - The head impulse test is a simple clinical test comprising high acceleration head
      rotation. In the presence of a severe unilateral vestibular weakness the normal
      vestibulo-ocular reflex is replaced by a misalignment of the eye followed by a
      series of corrective saccades which are evident to the examiner. Previous reports
      have shown the high sensitivity of the head impulse test in detecting complete
      unilateral weakness, but indicate poor sensitivity for mild weaknesses. This
      prospective, blinded study examined the head impulse test in a general clinical
      population of balance disorder patients to examine the sensitivity and
      specificity of the test, and to determine the degree of vestibular weakness that
      is required before the test becomes positive. One hundred and fifty patients were
      examined and the head impulse test results were compared to results from
      bithermal caloric testing. Results show that the overall sensitivity of the head
      impulse test is 34% with a specificity of 100%. The test does not detect mild or
      moderate vestibular weaknesses but is very sensitive to the presence of a severe
      paresis (87.5%). Head impulse testing will not replace caloric testing but is a
      very useful adjunct to it.

PMID- 9597281
TI  - Bilateral stapedotomy in patients with otosclerosis: a disability-orientated
      evaluation of the benefit of second ear surgery.
AB  - This study reports the evaluation of the results of 80 stapedotomies in patients
      with bilateral otosclerosis. All pre- and postoperative audiological data,
      together with all relevant information of the operations, were stored in a
      database and analysed retrospectively. A new approach has been developed in order
      to evaluate the benefit of second ear stapes surgery in a more disability
      orientated way using the AMA-criteria in the Guides to the Evaluation of
      Permanent Impairment. In all patients the percentage of Binaural Hearing
      Impairment (BHI) and the percentage of Impairment of the Whole Person (IWP) were
      determined according to the AMA-criteria. In patients who had both operations at
      the Academic Medical Centre it was found after the first operation that there was
      an important decrease in the BHI-percentage (from 26% to 10%) as well as for the
      IWP-percentage (from 9% to 4%). In addition, the percentages dropped
      significantly after the second operation (from 11% to 7% and from 4% to 2%,
      respectively). During follow-up there were no serious complications. It is
      concluded that bilateral stapedotomy is a safe procedure with good results.

PMID- 9597283
TI  - Flow cytometric analysis of nuclear DNA content in oral leukoplakia.
AB  - DNA ploidy has been studied in 31 paraffin-embedded specimens of oral leukoplakia
      and in 10 specimens of oral leukoplakia that have undergone malignant
      transformation after a 5-year observation period. Three out of 31 specimens
      (9.7%) showed an aneuploid DNA pattern, with DNA indices of 1.17, 1.28 and 1.32.
      It was not possible to establish a statistically significant difference of DNA
      ploidy related to the presence or absence of dysplasia. One out of the 10 oral
      leukoplakias that underwent malignant transformations had a multiploid pattern
      with DNA indices of 1.44 and 2.37. In this study the DNA index has not proved to
      be of value in the identification of dysplastic leukoplakia among the non
      dysplastic ones.

PMID- 9597282
TI  - The clinical role of specific IgE and IgG4 antibodies in patients having
      immunotherapy for seasonal allergic rhinitis.
AB  - This study was designed to investigate the clinical role of specific IgG4 and IgE
      responses in patients during immunotherapy for seasonal allergy. The study
      included 109 patients with seasonal allergic rhinitis due to Japanese cedar
      pollens. They were divided into the control group and the immunotherapy group.
      Serum samples were obtained at the start of immunotherapy, before the pollen
      season and during the season, to determine serum specific IgE and IgG4. In the
      control group specific IgE was significantly increased, but specific IgG4 was not
      changed during the pollen season. In the immunotherapy group specific IgE was not
      significantly increased, but specific IgG4 was significantly increased during the
      season. In the patients having immunotherapy for 2 years or less, the seasonal
      increase in specific IgG4 related to the magnitude of the clinical effect. In the
      patients having immunotherapy for 3 years or more, the seasonal increase in
      specific IgE related to the magnitude of the clinical effect. In conclusion, the
      specific IgG4 response and specific IgE response during the pollen season make a
      significant contribution to the clinical effect of immunotherapy. However,
      modulation of specific IgE and IgG4 responses out of the pollen season was
      unlikely to be an important phenomenon related to the clinical effect of
      immunotherapy.

PMID- 9597284
TI  - The effects of computer simulated facial plastic surgery on social perception by
      others.
AB  - Previous studies have demonstrated the remarkable impact of facial plastic
      surgery on the perception of facial features. However, pre- and postoperative
      differences other than the surgically changed features such as facial expression,
      hairstyle, make-up etc., have influenced the results of previous studies. To
      exclude these visual cues a computer composite photograph of the changed feature
      mounted upon the preoperative photograph, instead of the standard postoperative
      photograph, was presented to observers in this study. Computer graphic technology
      was used to superimpose the postoperative, surgically changed facial features
      such as the nose, ear and chin of 16 patients on standardized preoperative
      photographs. The randomized preoperative photographs and the 'postoperative'
      composed images were presented to 67 subjects, using a person-perception
      questionnaire. Multivariate analysis demonstrated a more favourable postoperative
      judgement in only two patients (12.5%). The exclusive effect of facial plastic
      surgery on the social perception of patients by others when excluding visual
      cues, such as facial expression, hairstyle, make-up etc, is limited. It is
      tentatively assumed that the role played by facial plastic surgery is one of
      initiating a positive cycle by changing the patient's self-perception rather than
      one of direct social impact from the changed features.

PMID- 9597285
TI  - The relation between tonsillectomy and snoring.
AB  - The aim of this study was to determine the relation between snoring and
      tonsillectomy. The grossly enlarged tonsils of a heavily snoring child or adult
      with upper airway obstruction is usually sufficient indication for tonsillectomy.
      The authors wondered if tonsillectomy could affect snoring, no matter what the
      age and the indication for surgery. One thousand people took part in this study:
      a random sample of patients aged between 2 and 89 years of age, and those
      accompanying them in the ENT outpatients. The prevalence of snoring was 12.5-48%,
      mainly in men. The degree of snoring was graded from non-snorers to mild,
      moderate and severe snorers. In 19.8% of the sample tonsillectomy had already
      been performed, usually in childhood. The authors conclude that tonsillectomy
      does not reduce the likelihood of becoming a snorer.

PMID- 9597286
TI  - Endoscopic inferior dacryocystorhinostomy.
AB  - Conventional dacryocystorhinostomy (DCR) usually involves extensive removal of
      bone at the lacrimal fossa and hence risks disruption of the lacrimal pump
      mechanism. A physiological operation for nasal lacrimal blockage is described
      whereby only the inferior portion of the lacrimal sac and the adjacent duct are
      marsupialized into the nose. The operation is safe, quick and does not involve
      sophisticated instruments. Result of 81 consecutive endoscopic inferior DCRs
      reveals a success rate of over 90% which is maintained with time. Most patients
      had a wide lacrimal window with preserved lacrimal pump movement at the superior
      sac remnant.

PMID- 9597287
TI  - Metastatic squamous cell carcinoma in cervical lymph nodes from an unknown
      primary tumour: prognostic factors.
AB  - The aim of this retrospective review is the study of the prognostic factors
      related to cervical metastases of squamous cell carcinoma from an unknown primary
      tumour. Sixty-seven patients were selected and surgery and postoperative
      radiotherapy was the treatment used. Nineteen tumours were subsequently found
      (27%). The 5-year actuarial survival rate of all patients was 22%. Survival rates
      were significantly related to lymph node stages and to the histological degree of
      differentiation. Nevertheless, actuarial survival rates were not related to the
      appearance of the primary tumour (P = 0.07). In our series, the single most
      important prognostic factor was the neck stage. The value close to statistical
      significance observed when the primary tumour subsequently appeared (P = 0.07),
      suggests that this could worsen the prognosis.

PMID- 9597288
TI  - Microbiology and antibiotic treatment of head and neck abscesses in children.
AB  - The clinical data, microbiological results and antibiotic treatment of 65
      children who have required incision and drainage of suppurative head and neck
      abscesses was retrospectively investigated with the aim of developing a more
      effective clinical protocol of treatment, improving speed of resolution and
      rationalizing the need for surgical intervention. A positive culture grew in 78%
      of children and of these 45% were Staphylococcus aureus, 9% Streptococcus
      pyogenes, and 8% atypical mycobacteria. Only 3% of the samples grew anaerobes.
      All isolates of S. aureus were sensitive to Flucloxacillin and all isolates of S.
      pyogenes were sensitive to penicillin. All anaerobes were Metronidazole
      sensitive. In 40% of the children there were no localizing symptoms which could
      guide the treatment, therefore we recommend Flucloxacillin and Metronidazole as
      the antibiotic regimen of choice in acute suppurative lymphadenitis. The
      increasing incidence of atypical mycobacterial lymphadenitis is noteworthy.

PMID- 9597289
TI  - Efficacy of external fixation following nasal manipulation under local
      anaesthesia.
AB  - Nasal fractures are one of the commonest reasons for patients being referred to
      ENT departments, but few studies have been published about the management of this
      condition. In particular, the efficacy of external splintage following
      manipulation has not been assessed. This was a prospective randomized study,
      which examined the results of manipulation under local anaesthetic and the
      benefit to be gained from external fixation with Plaster of Paris (POP) following
      this procedure. Accurate measurements of the degree of deviation of the nose pre-
      and post-manipulation were obtained using a camera mounted on a specially
      designed frame. Thirty-three out of 241 consecutive patients seen at a research
      clinic over the course of 12 months were included in the study. The mean
      deviation of the nasal bridge at presentation was 4.12 mm. Manipulation under
      local anaesthetic significantly improved the degree of deviation (mean 2.47 mm, P
      = 0.0011, 90% CI, 1-2 mm). Randomization of the patients, following manipulation,
      into POP/none-POP groups showed that external splintage of the nose appeared to
      be of little practical benefit.

PMID- 9597290
TI  - Treatment of oropharyngeal carcinoma by irradiation or by surgery.
AB  - Of previously untreated patients with squamous cell carcinoma of the oropharynx,
      145 are reviewed in this study. All were treated in the Department of Head and
      Neck Surgery at the University of Liverpool from 1990 to 1997. Seventy-seven
      patients were treated with irradiation, 28 patients by surgery and 40 patients
      were deemed not suitable for any curative treatment. Univariate analysis showed
      no difference in the two groups treated by curative modalities but multivariate
      analysis did suggest that the surgical group tended to have larger neck node
      metastases. The 5-year tumour specific actuarial survival for all patients was
      53%, 65% for the radiotherapy group and 51% for the surgery group. The difference
      was not statistically significant (chi (1)2 = 1.5070). The modality of treatment
      had no affect on either the development of a primary or neck node recurrence or
      the survival after such a recurrence. Where neck node disease was present it was
      treated as appropriate. As is generally standard practice, lymph nodes over 2 cm
      were treated with radical neck dissection whether the patient was having
      irradiation therapy or surgery. If the patient was having irradiation therapy,
      the neck dissection was carried out before and irradiation after operation, both
      on the primary and on the neck, if appropriate. It is concluded that irradiation
      therapy in properly selected cases in combined head and neck clinics is a safe
      and effective treatment for squamous cell carcinoma of the oropharynx. Neck node
      disease should be treated appropriately, but there is no support for the old
      adage that whatever form of treatment is being used for the neck node should also
      be used for the primary site.

PMID- 9597291
TI  - The results of chronic ear surgery in a training programme.
AB  - A retrospective study was undertaken of the results of surgery in a series of 782
      patients with chronic otitis media. The recurrence rate of cholesteatoma was 20%
      of patients operated on by trainees and 12% operated on by the faculty. In ears
      with granulating otitis media, control of infection was achieved by trainees as
      often as by the faculty. The tympanic membrane healing rate of myringoplasty and
      tympanoplasty operations was 78% for trainees and 95% for the faculty (P <
      0.001). Major surgical complications were relatively rare. It is concluded that
      the performance of trainees was fairly safe and better than expected, but some
      failures might have been prevented by closer supervision. Because of the decline
      in available patients for chronic ear surgery, it is suggested that the training
      programme should be restructured so that only those trainees who wish to pursue
      otological surgery as a career are trained in this field.

PMID- 9597292
TI  - Bacteriology of normal and diseased tonsils assessed by fine-needle aspiration:
      Haemophilus influenzae and the pathogenesis of recurrent acute tonsillitis.
AB  - The pathogenesis of recurrent tonsillitis is largely unknown. Selection of
      appropriate antibiotic therapy for patients with recurrent tonsillitis is
      difficult because of the limitations of traditional methods of sampling tonsillar
      microflora and the increasing incidence of beta-lactamase producing bacteria in
      the tonsil. In addition, little attention has been paid to the bacteriology of
      normal tonsils. The tonsil core bacteria was assessed in 124 patients with
      recurrent acute tonsillitis. Fifty-five of these patients were randomly selected
      for fine-needle aspiration which revealed a similar profile of bacteria in 85%.
      Fine-needle aspiration of 10 normal tonsils found few pathogens; the predominant
      organisms being normal flora. No Haemophilus influenzae were detected in this
      control group. This study demonstrates the accuracy of fine-needle aspiration in
      identifying tonsil core bacteriology and its suitability in the clinical setting.
      It reports on the flora of normal healthy tonsils and it highlights the
      association between H. influenzae and recurrent acute tonsillitis.

PMID- 9597293
TI  - The Web, communication trends, and children's health. Part 3: The Web and health
      consumers.
AB  - The World Wide Web has the potential to change significantly how medical care is
      both delivered and consumed. This, the third of a five-part series on The Web,
      Communication Trends, and Children's Health, considers how families can use the
      Internet to find consumer health information and to access care. This article
      also discusses some of the potential and limitations of Web-based health
      resources. Part 1 of this series described the development and technology of the
      Internet and the Web. Part 2 suggested how pediatricians can use the Web to
      gather medical information and how the increasing capabilities of the Web may
      affect clinical practice.

PMID- 9597294
TI  - Suspecting lumbar spondylolysis in adolescent low back pain.
AB  - Spondylolysis in the athletic adolescent and preadolescent is common enough that
      primary care practitioners should be familiar with its frequency and its
      progression from pars interarticularis stress fracture to spondylolysis and to
      spondylolisthesis. One-half of all pediatric back pain in athletic patients is
      related to disturbances of the posterior elements including spondylolysis, which
      presents as low back pain aggravated by activity, frequently with minimal
      physical findings. Failure to suspect, hence to diagnosis, a pars stress fracture
      or early spondylolysis is common and a misdiagnosis of lumbosacral strain is
      often made. A complicating factor in early diagnosis is the fact that plain
      radiographs, even with oblique films, may not be helpful at the stress fracture
      stage, and other imaging techniques (bone scan possibly with single photon
      emission computed tomography [SPECT]) must be used early in the diagnostic
      process. In the primary care setting, an early diagnosis of posterior element
      involvement in low back pain either at the stage of pars stress fracture or early
      spondylolysis can prevent progression of the disease and the need for aggressive
      intervention for a more significant defect. We present three adolescent and
      preadolescent athletes with low back pain in whom a high index of suspicion led
      to the early diagnosis of pars stress fracture or spondylolysis. All three had
      different stages of spondylolysis, and one illustrates the clinical utility of
      the one-legged hyperextension test. The ease with which early disease may be
      treated further supports efforts by primary care practitioners to suspect and
      diagnose pars stress fracture and early spondylolysis.

PMID- 9597295
TI  - Neurofibromatosis type 1 in childhood: evaluation of clinical and epidemiologic
      features as predictive factors for severity.
AB  - The authors evaluated clinical and epidemiologic features of neurofibromatosis
      type 1 (NF-1) as predictive factors of severity of the disease. The data were
      retrieved from medical records of 110 children with NF-1 followed up during the
      period 1974-1991 (mean duration of follow-up 6.7 years). Presence of macrocephaly
      correlated with higher grade of severity of the disease (P = 0.018). Familial NF
      1 was more common in patients with grade 4 disease than in children with grade 1
      severity (P < 0.05; odds ratio 2.9, confidence limits 0.85-10.5). The specificity
      of positive family history and macrocephaly as predictive factors for the grade 4
      disease was 90% and 89%, respectively, and sensitivity was 71% and 36%,
      correspondingly. Positive predictive value of familial NF-1 and macrocephaly was
      24% and 31%, respectively. In conclusion, although patients with family history
      of NF-1 and with macrocephaly tend to have more severe disease, the clinical
      utility of these features as predictive factors for severity is limited.

PMID- 9597296
TI  - Discordant puberty in monozygotic twin sisters with neurofibromatosis type 1
      (NF1).
AB  - Monozygotic twin sisters are reported who have discordant pubertal growth and
      sexual development. Although both sisters were physiologically appropriate for
      chronological age in their pubertal development, their adolescent development was
      considerably different from that expected of monozygotic twin sisters. The more
      pubertally advanced sister by magnetic resonance imaging had an optic pathway
      glioma while none was present in her twin sister. Precocious puberty is not an
      unexpected complication of neurofibromatosis type 1 and is always associated with
      the presence of an optic pathway glioma. These sisters emphasize the striking
      similarity that is expected of monozygotic twins and the need for investigation
      when intertwin differences in growth and/or development arise.

PMID- 9597297
TI  - Characterization of failure to imbibe in infants.
AB  - The term failure to imbibe is proposed to describe infants with failure to thrive
      due to poor feeding. Feeding assessment was performed in 128 patients: 43 healthy
      controls, 53 diseased controls, 12 with nonorganic failure to thrive, and 20 with
      failure to imbibe. Infants with failure to imbibe required a significantly longer
      time to feed compared with other infants. In contrast to other infants with
      nonorganic failure to thrive, patients with failure to imbibe were more likely to
      need pediatric subspecialty care and nasogastric or gastrostomy tube feeding.
      Since these patients may have treatable conditions, infants with failure to
      imbibe merit further investigation.

PMID- 9597298
TI  - Use of the rectal examination on children with acute abdominal pain.
AB  - The purpose of this study was to determine the frequency with which general
      pediatricians perform a rectal examination on children with a complaint of acute
      abdominal pain and to determine factors associated with performing a rectal
      examination. Children were eligible for the study if they were 2 to 12 years of
      age and presented to the clinic or emergency department of a municipal teaching
      hospital with a complaint of abdominal pain of less than or equal to three days'
      duration. Measured variables included demographic characteristics and presenting
      signs and symptoms. For each patient, a clinical reviewer (1) assigned a final
      diagnosis, (2) determined whether a rectal examination had been performed, and
      (3) assessed the clinical contribution of the rectal examination findings. For
      1,140 children presenting for a nonscheduled visit with acute abdominal pain, a
      rectal examination was performed on 4.9% (56/1,140). Using multiple logistic
      regression, children were more likely to have a rectal examination performed if
      they had abdominal tenderness (odds ratio [OR] = 3.3 and 95% confidence interval
      [CI], 1.8 to 6.0), a history of constipation (OR = 6.0 and 95% CI, 2.3 to 15.3),
      or a history of rectal bleeding (OR = 9.1 and 95% CI, 2.9 to 29). Children were
      less likely to have had a rectal examination performed if they presented with
      associated symptoms of cough (OR = 0.32 and 95% CI, 0.14 to 0.74), headache (OR =
      0.15 and 95% CI, 0.05 to 0.46), or sore throat (OR = 0.28 and 95% CI, 0.08 to
      0.91). The final diagnoses of 12 children who had clinically contributory
      findings on rectal examination included: constipation (5), gastroenteritis (3),
      appendicitis (2), abdominal adhesions (1), and abdominal pain of unclear etiology
      (1). General pediatricians infrequently perform a rectal examination on children
      who present with a complaint of acute abdominal pain. Clinical factors affect the
      likelihood of whether a rectal examination is performed.

PMID- 9597299
TI  - A child with chest pain.

PMID- 9597300
TI  - Rohypnol, the date rape drug.

PMID- 9597301
TI  - "Flocculus neonatorum": a self-resolving benign nodular flocculus of the iris in
      the newborn.

PMID- 9597302
TI  - Collaborative office rounds between pediatricians and child psychiatrists.

PMID- 9597303
TI  - New emerging zoonoses: a challenge and an opportunity for the veterinary
      profession.
AB  - The concept of emerging infectious diseases appeared in the late 1980s, when
      major outbreaks occurred around the globe and surprised many scientists who
      considered infectious diseases to be maladies of the past or limited to the under
      developed world. Several reports identified erosion of the public health
      infrastructure among the factors contributing to new and re-emerging infectious
      diseases. As indicated by Morse, "Disease emergence often follows ecological
      changes caused by human activities such as agriculture or agricultural change,
      migration, urbanization, deforestation, or dam building". "Among these new
      diseases, surprisingly, most emergent viruses and many emergent bacteria are
      zoonotic". Several new zoonoses have been recently identified. Many of these
      diseases were either unknown, because we were not able to isolate the infectious
      agent or to distinguish them from other clinical syndromes, or discovered
      accidentally. Much of the recent identification of new pathogens has been based
      on new molecular biology tools or epidemiological studies. For all these diseases
      or infections, veterinarians played a key role in their identification, isolation
      of the causative organisms and understanding of the epidemiology of the
      infection. The role of the veterinary profession is very important in public
      health and on the rise again in the U.S.A., as it should be in many other
      countries. Surveillance, clinical curiosity and awareness, epidemiology and
      laboratory training are the essential tools and competency that the veterinary
      profession must use to meet the challenge of new emerging zoonoses.

PMID- 9597304
TI  - Cytokines and the protective host immune response to Chlamydia psittaci.
AB  - The immunobiology of enzootic abortion of ewes (EAE) is incompletely understood.
      The causative agent is Chlamydia psittaci, which infects many ruminant species
      and has zoonotic potential. The organism can survive in the ovine host for many
      months without causing clinical symptoms but does not generate a sterile immunity
      during this time. It has been postulated that the organism persists in the host
      entering at a latent phase, possibly mediated by host cytokine production. The
      effects of cytokines on chlamydial multiplication vary between host species,
      between different cell types within those species and also vary between
      chlamydial species and strains. The multiplication of the EAE strain of C.
      psittaci in ovine ST-6 cells can be restricted by interferon-gamma (IFN-gamma)
      but not with comparable concentrations of IFN-alpha. Altering the nutrient
      composition of the cultures by addition of tryptophan partially reverses the
      antichlamydial effects of the IFN-gamma. This offers a potential mechanism by
      which C. psittaci can persist in sheep. The implications of these observations
      for the pathogenesis of EAE are discussed.

PMID- 9597305
TI  - Clinicopathological and immunological characteristics of six cats with granular
      lymphocyte tumors.
AB  - Clinical and immunological characteristics were investigated in six cases of
      feline granular lymphocyte (GL) tumor. The ages of the affected cats were
      relatively old, ranging from 4 to 13 years of age. Gastrointestinal signs were
      commonly observed in these cases. Only one of the six GL tumor cases was positive
      for feline leukemia virus (FeLV) antigen. Phenotypic analysis revealed that the
      GL tumor cells from all of the six cases lacked the T- or B-cell markers. These
      GL tumor cells were examined by Southern blot analysis using feline
      immunoglobulin (Ig) and T-cell receptor (TCR) gene probes. GL tumor cells
      obtained from two cases were identified as cells of T-cell lineage by the
      presence of a rearranged TCR beta gene, whereas those from the other four cases
      were considered to be derived from non-T- non-B-cell lineage because of the
      absence of rearrangement of these genes. These findings indicated that feline GL
      tumors can be considered as a specific disease entity in feline lymphomas because
      the cases examined in this study showed onset at an older age, a low incidence of
      FeLV infection and frequent involvement of gastrointestinal lesions, which are
      not found in typical FeLV-associated lymphomas. Although no specific phenotypes
      was observed by phenotypic analysis, the feline GL tumor cells were divided into
      two consistent genotypes of T-cell or non-T- non-B-cell lineages.

PMID- 9597306
TI  - Aeromonas hydrophila septicaemia in a grey seal (Halichoerus grypus) from the
      Baltic Sea: a case study.
AB  - Aeromonas hydrophila septicaemia in a grey seal (Halichoerus grypus) from the
      Swedish part of the Baltic Sea is reported. The pathogen was isolated from both
      lung and spleen specimens. All of the A. hydrophila isolates produced haemolysin
      and Vero active cytotoxin. The aerolysin gene was found in all tested isolates as
      evidenced by the polymerase chain reaction (PCR) technique. Also, all isolates
      tested showed identical patterns of biochemical and antibiotic resistance. As
      Aeromonas spp. commonly occur in aquatic environments, we suggest that organisms
      from this genus may also play an important role as opportunistic pathogens in
      morbillivirus infected seals.

PMID- 9597307
TI  - Variability of antigenic epitopes of the fusion protein of Newcastle disease
      virus.
AB  - Using a panel of 10 monoclonal antibodies (Mab) against fusion (F) protein of
      Newcastle disease virus (NDV), strain Australia-Victoria, three non-overlapping
      antigenic sites (F1, F2 and F3) and one site partially overlapping with the sites
      F1 and F2 (F1.2) have been identified. The sites F2 and F3 are clusters that each
      include four antigenic epitopes. The antigenic stability of the above epitopes
      was estimated by comparison of the binding capacity of the corresponding Mabs
      towards 63 NDV strains isolated in different years and places from various avian
      species. The results demonstrated high variability of the site F1.2 and of all
      the four epitopes of the site F2. At the same time, the only epitope of the site
      F1 can be defined as highly conservative: the corresponding Mab gave positive
      binding with 60 from 63 NDV strains, one from the four epitopes pertaining to
      site F3 was the most conservative--the corresponding Mab reacted with all the 63
      strains used in the studies, while the other three Mabs showed rather low
      stability--the corresponding Mabs reacted with 34-39 NDV strains. Thus, as
      opposed to the published data asserting antigenic stability of the F protein
      contrary to the high variability of the haemagglutinin-neuraminidase (HN)
      protein, our results have revealed a number of variable epitopes on the F
      protein. This demonstrates an evolutionary changeability of the F protein, which
      is of importance from the theoretical (viral antigenic evolution) as well as
      practical point of view.

PMID- 9597308
TI  - Isolation and characterisation of immunoglobulin g and IgG subclasses of the
      African elephant (Loxodonta africana).
AB  - Immunoglobulins were precipitated from pooled African elephant sera with ammonium
      sulphate and separated by gel filtration and fast protein liquid chromatography
      (ion exchange). Analysis of the fractions by SDS-PAGE showed IgG of 150 kDa with
      up to five subclasses, each having heavy chains of 57 kDa and light chains of 27
      kDa. Three monoclonal antibodies against human IgG and polyclonal antibodies
      against canine, bovine, cameline, equine, phocine and feline IgG showed strong
      cross-reactivity with the African elephant IgG subclasses. No serum molecules
      corresponding to IgM or IgA could be detected, even when ammonium sulphate
      precipitation was used at 50% saturation.

PMID- 9597309
TI  - A mass outbreak of gastroenteritis associated with group C rotaviral infection in
      schoolchildren.
AB  - In 1988, a mass outbreak of epidemic diarrhea, i.e., consisting of 296 cases,
      occurred in Fukuoka Prefecture. Fecal samples from patients of the outbreak were
      cultured for bacteria, but all samples were negative. Although direct electron
      microscopy (DEM) revealed the existence of rotavirus-like particles (diam. 60-70
      nm) in the fecal samples, serological studies could not detect any antigenic
      relation to the ordinary rotaviruses by the reverse passive hemagglutination
      (RPHA) and enzyme-linked immunosorbent assay (ELISA) tests or immune electron
      microscopy (IEM) examination. The outbreak appeared to be caused by group C
      rotaviruses, based on the pattern of electrophoretic migration of RNA genome
      segments in polyacrylamide gel electrophoresis (PAGE). Furthermore, IEM
      examination showed large aggregates of virus particles and antibodies when the
      virus particles were incubated with a reference serum specific for group C
      rotaviruses.

PMID- 9597310
TI  - Skin imaging: state of the art at the dawn of the year 2000.

PMID- 9597311
TI  - In vivo proton magnetic resonance spectroscopy in human skin.

PMID- 9597312
TI  - Raman spectroscopy and skin.

PMID- 9597313
TI  - Optical coherence tomography of the skin.

PMID- 9597314
TI  - Examination of stratum corneum hydration state by electrical methods.

PMID- 9597315
TI  - Optothermal measurement of water distribution within the stratum corneum.

PMID- 9597316
TI  - An improved method for the measurement of scalp sebum.

PMID- 9597317
TI  - Mechanical function of the skin: state of the art.

PMID- 9597318
TI  - Thermal sensory analyzer. Boon to the study of C and A delta fibers.

PMID- 9597319
TI  - Cutaneous microdialysis. A new technique for the assessment of skin penetration.

PMID- 9597320
TI  - A new method for assessing, in vivo in human subjects, the basal or UV-induced
      peroxidation of the stratum corneum. Application to test the efficacy of free
      radical-scavenging products.

PMID- 9597321
TI  - Biophysical methods for disease monitoring in dermatology.

PMID- 9597322
TI  - Skin bioengineering in phlebology and angiology.

PMID- 9597323
TI  - Skin bioengineering methods in the monitoring of scleroderma.

PMID- 9597324
TI  - Skin bioengineering methods in occupational dermatology.

PMID- 9597325
TI  - Climatic influence on cosmetic skin parameters.

PMID- 9597326
TI  - Lipid content and electrical impedance.

PMID- 9597327
TI  - Evaluation of the short-term effects of skin care products: a comparison between
      capacitance values and echographic parameters of epidermal hydration.

PMID- 9597328
TI  - Assessment of skin hydration caused by diapers and incontinence articles.

PMID- 9597329
TI  - Analysis of cuticle relief for hair photoprotection evaluation. Validation study.

PMID- 9597330
TI  - Legal situation and study of efficacy and tolerability of topical products on
      human skin using non-invasive methods.

PMID- 9597331
TI  - Designing and performing clinical studies with bioengineering techniques.

PMID- 9597332
TI  - Correlation of in vitro and in vivo testing.

PMID- 9597333
TI  - Possible pitfalls in hydration measurements.

PMID- 9597334
TI  - Physical measurements for the predictive evaluation of the tolerability of skin
      products.

PMID- 9597335
TI  - Root instrumentation. Power-driven versus manual scalers, which one?
AB  - The literature is clear that periodontal therapies aimed at altering the
      progression of inflammatory periodontal diseases must include meticulous
      subgingival mechanical debridement during both the nonsurgical and the surgical
      phases of treatment as the basis of most anti-infective therapy. In the past,
      infection control was achieved by the mechanical removal of subgingival deposits
      of plaque, calculus, and endotoxin with curets, files, and hoes. Historically, it
      was also generally agreed that aggressive scaling and root planing with hand
      instruments was necessary to remove tenacious calculus deposits to produce roots
      as smooth as possible for removal of the endotoxins previously thought to be
      deeply embedded into the root surfaces. Based on current evidence in the
      literature, it is now known that endotoxin is a weakly adherent surface
      phenomenon and that sonic and ultrasonic (power-driven) instruments can be used
      to accomplish definitive root detoxification and maximal wound healing without
      overinstrumentation of root and without extensive cementum removal. Power-driven
      scalers may have unique advantages because of the cavitational activity
      associated with ultrasonics thought to supplement removal of root surface
      plaques. In addition, the constant flushing activity of the lavage used to cool
      the tips results in disruption of the unattached and weakly attached subgingival
      plaques. The ability to flush the pocket during subgingival instrumentation with
      water or other chemical irrigating solutions is unique to ultrasonic and sonic
      scalers and has been shown to enhance pocket depth reduction and gain in clinical
      attachment beyond that achieved with hand scaling. The added benefit of chemical
      lavage during ultrasonic instrumentation shows great promise and may enhance the
      overall effect of nonsurgical anti-infective periodontal therapy. Other major
      advantages of power-driven scalers may include better access to difficult areas,
      such as deep narrow defects, root grooves, and furcations, using newly designed
      microultrasonic tips, which are smaller in diameter and able to penetrate the
      pocket approximately 1 mm farther than hand instruments. Taken together, it
      appears that use of ultrasonic or sonic scalers for periodontal debridement will
      result in improvements in clinical and microbial parameters at a level equal to
      or superior to hand scalers.

PMID- 9597336
TI  - Pharmacologic management of periodontal diseases using systemically administered
      agents.
AB  - Since the establishment of bacteria-laden plaque as a causative agent in
      gingivitis, the search for specific bacteria that induce different types of
      periodontitis has generated extensive research. In contrast to many other
      microbial-induced disorders, the specific periodontal pathogen(s) has not been
      identified to date. Therefore, the search for an effective systemic agent to
      prevent the loss of attachment through the selective reduction of known
      periodontal pathogens has remained elusive. It is not surprising then that
      antibiotics are not used solely to manage periodontal diseases but rather as an
      adjunct to the mechanical debridement of root surfaces in select periodontal
      diseases. Further, the sole use of antibiotics in patients with adult
      periodontitis (or those who exhibit signs of inflammation but are periodontally
      stable) has shown little benefit and only increases the chance of microbial
      resistance to antibiotics. Despite these limitations, considerable progress in
      antibiotic therapy has delivered regimens that enhance the effectiveness of
      conventional therapy. In contrast to traditional antimicrobial therapy, new
      treatment modalities have begun to focus on modulating the responses of host
      cells to bacteria rather than modulating only the bacteria. Current drugs used to
      regulate host cells inhibit the cyclooxygenase pathway, reduce the activity of
      metalloproteinases, or inactivate bone resorptive cells (see Table 1). Although
      these drugs offer great potential to modulate a variety of mammalian cells, a
      notable and consequential limitation of these agents is a lack of specificity.
      Inflammation, bone metabolism, and connective tissue metabolism are two-edged
      swords; all are necessary for the homeostasis of the tissue, but some or all may
      also be involved in the pathologic destruction of that same tissue. Hence, drugs
      that inhibit destruction of the connective tissue in one site of the periodontium
      also interfere with wound healing at another. As a result of these limitations,
      the efficacy, safety, and cost-effectiveness of the long-term use of these agents
      is unknown. Preliminary results of treatment with these drugs are promising, and
      future generations of host-modulating drugs will provide clinicians with
      additional agents to help improve the success rate of periodontal treatment for
      patients. Antibiotics remain an important adjunctive therapy in the treatment of
      periodontal diseases, and the use of host modulating drugs as supplemental agents
      in the management of periodontal diseases continues to grow. As more knowledge is
      gained about the causes of periodontal diseases, new drugs that are potent,
      effective, site specific, and safe can be delivered at optimal times by simply
      having the patient take a few tablets. Considering the dramatic progress in the
      past decade in understanding the cause and pharmacologic management of
      periodontal diseases, the twenty-first century holds great promise for the
      development of magic bullets.

PMID- 9597337
TI  - Controlled local delivery of antimicrobials in the treatment of periodontitis.
AB  - Five local delivery systems with five different antimicrobial agents have been
      discussed. All are capable of delivering high concentrations of their
      antimicrobial to the site of the periodontal infection. Although only one system,
      tetracycline fiber, is available in United States, two other systems,
      chlorhexidine chip and doxycycline polymer, may be available in the near future.
      Two other systems, metronidazole gel and minocycline ointment, are available in
      other countries. Data from pertinent studies were presented as were techniques
      for using the various systems. Indications for the use of the products were also
      discussed. In selecting the appropriate delivery system, the clinician has to
      weigh the efficacy of the products, ease of use, availability, and cost. Although
      local delivery systems do not replace existing periodontal therapies, they do
      have a place in the treatment of periodontitis and offer the dentist additional
      methods to aid in the control of periodontal diseases.

PMID- 9597338
TI  - Changing concepts. The effects of occlusion on periodontitis.
AB  - Despite volumes of publications on the theory of occlusion, occlusal design, and
      equilibration techniques, there have been few well-designed human studies
      directed at answering the question does occlusal trauma modify the progression of
      attachment loss in periodontitis. The articles reviewed indicate that occlusal
      forces can cause changes in the alveolar bone and periodontal connective tissue
      both in the presence and in the absence of periodontitis. These changes can
      affect tooth mobility and clinical probing depth. Although occlusal forces do not
      initiate periodontitis, results are inconclusive as to if or how these forces
      affect attachment loss owing to plaque-induced inflammatory periodontal disease.
      Although some studies reported a relationship between increased attachment loss
      and tooth mobility, others found no relationship between attachment loss and
      abnormal occlusal contacts. Tooth mobility results from a variety of factors,
      including alveolar bone loss, attachment loss, disruption of the periodontal
      tissues by inflammation, widening of the PDL in response to occlusal forces
      (physiologic adaptation), PDL atrophy from disuse, and other processes that
      effect the periodontium. Therefore, any relationship found between tooth mobility
      and progressing periodontitis does not necessarily implicate or defend occlusion
      as a cofactor in the progression of inflammatory periodontal disease.
      Periodontitis can be treated and periodontal health maintained without occlusal
      adjustment and in the presence of traumatic occlusal forces. Statistically
      greater gains in clinical periodontal attachment level have been reported,
      however, when occlusal adjustment was included as a component of periodontal
      therapy. The extent to which this is clinically meaningful is unclear. Once
      periodontal health is established, occlusal therapy can be used to reduce
      mobility, to regain bone lost owing to traumatic occlusal forces, and to treat a
      variety of clinical problems related to occlusal instability and restorative
      needs. The clinician's decision whether or not to use occlusal adjustment as a
      component of periodontal therapy should be related to an evaluation of clinical
      factors involving the patient's comfort and function and not based on the
      assumption that occlusal adjustment is necessary to stop the progression of
      periodontitis.

PMID- 9597339
TI  - The diagnosis and treatment of molar furcation invasions.
AB  - Multirooted teeth with FI present some of the biggest challenges in periodontal
      therapy despite a large arsenal of therapeutic techniques. Guided tissue
      regeneration has improved the long-term prognosis of many deep grade II lesions
      but has not always shown consistent predictability. With improved barrier
      techniques and the development of effective growth factors, however, guided
      tissue regeneration may well become the treatment of choice for all grade II and
      III FI. Until that time, early diagnosis and treatment are critical to long-term
      success. Even strategically important teeth with more advanced FI often have a
      much better long-term prognosis than previously believed and can survive for many
      years, even with closed scaling and root planning and frequent, long-term
      maintenance. Before condemning molars with severe FI, clinicians should consider
      their experience in treating advanced periodontal diseases and seek consultation
      with a specialist when in doubt as to the prognosis and treatment of teeth with
      significant FI.

PMID- 9597340
TI  - Periodontal microsurgery.
AB  - Practitioners of periodontics must have familiarity with the various methods of
      optical magnification and, ultimately, the surgical microscope, if they are going
      to refine their basic surgical techniques with improved visual acuity, as other
      areas of medicine and dentistry are doing. Macroscopic versus microscopic vision
      determines the degree to which surgeons can handle soft and hard tissue for
      primary wound closure and rapid, non-traumatic healing. Subtle basic
      microsuturing techniques offer vast improvement in wound closure through
      magnification and good visual feedback, as opposed to the tactile information
      traditionally taught in conventional suturing. Periodontal microsurgery began
      with mucogingival surgery, but has application in every area of periodontal
      therapy for those who become proficient in this challenging new area of
      technology.

PMID- 9597341
TI  - Biologic modifiers in periodontal regeneration.
AB  - The specific objective of this article was to update the reader on biologic
      modifiers being used or suggested for use in therapies directed at regenerating
      periodontal tissues. As indicated from the studies presented here, many of these
      biologic modifiers have significant influences on cell behavior and show great
      promise for use in regenerative therapies. As discussed here, however, additional
      investigations are required both at the molecular level and at the clinical level
      to improve the predictability of regenerative therapies. With active
      investigations directed toward understanding the biology of the healing site,
      including identifying appropriate cells to target, coupled with designing
      delivery systems that can control release of agents at the local site,
      establishing the required environment for regeneration of periodontal tissues
      should be feasible.

PMID- 9597342
TI  - How patient compliance to suggested oral hygiene and maintenance affect
      periodontal therapy.
AB  - 1. In medicine and dentistry, compliance tends to be poor in patients who have
      chronic diseases that they perceive as nonthreatening. 2. Even in the most
      optimistic studies, the rate of complete compliance with suggested toothbrushing
      is less than 50%; other studies show it much lower. In studies focusing on the
      use of interproximal cleaning aids, compliance is poorer still. 3. Patients in
      university-based programs have had a dropout rate (noncompliance) of 11% to 45%.
      In private periodontal practices, complete compliance was seen in one third or
      less of the patients. 4. The nature and the rate of disease progression affect
      SPT. The converse is also true. 5. In studies of the effect of therapy, it would
      be beneficial to record the results of treatment on all the patients, even those
      who drop out of therapy, to determine the part SPT plays in stabilizing the
      disease. 6. Patients fail to comply for many reasons, including self-destructive
      behavior, fear, economic factors, health beliefs, stressful events in their
      lives, and perceived dentist indifference. 7. By recognizing the problem,
      compliance can be improved in most patients. 8. There is a need for studies to
      define further the extent to which SPT affects the longevity of the dentition.

PMID- 9597343
TI  - Long-term nature of depression.

PMID- 9597344
TI  - Synergistic benefits of serotonin and noradrenaline reuptake inhibition.

PMID- 9597345
TI  - Efficacy of mirtazapine in clinically relevant subgroups of depressed patients.
AB  - Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA)
      with a novel mode of action that differs from other antidepressants that are
      currently available. Clinical trials have demonstrated it to have good
      antidepressant efficacy and excellent tolerability. Analysis of the results of
      placebo-controlled trials in moderately or severely depressed patients have shown
      mirtazapine to be effective in clinically important subgroups of depressed
      patients, particularly anxious patients, patients with sleep disturbance,
      retarded patients, and agitated patients. The efficacy and tolerability of
      mirtazapine are attributable to its pharmacological profile. It is likely that
      the overall antidepressant activity arises from its dual action, enhancing both
      noradrenergic and 5-HT1 receptor-mediated serotonergic neurotransmission, while
      the anxiolytic and sleep-improving properties of mirtazapine are attributable to
      the specific blockade of 5-HT2 and 5-HT3 receptors.

PMID- 9597346
TI  - SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis
      of efficacy and tolerability.
AB  - A meta-analysis of the efficacy and tolerability of selective serotonin reuptake
      inhibitors (SSRIs) against nonselective and noradrenergic reuptake inhibitors
      (mainly tricyclic antidepressants, TCAs) in depressed inpatients was carried out.
      Twenty-five double-blind studies provided data on relative efficacy which was
      determined by a summary variance-weighted mean effect size calculated from the
      difference in the reduction in mean Hamilton Depression Rating Scale (HDRS)
      scores for the two antidepressants in each study. Twenty-three studies provided
      data on dropouts and relative tolerability which was determined as the variance
      weighted pooling of the relative risk (RR) of dropout for all reasons and for
      adverse effects from each study. TCAs were significantly more effective than
      SSRIs (effect size = -0.23, 95% CI -0.40 to -0.05, P = 0.011), although
      sensitivity analyses by analysing larger studies (> 100 patients) and those
      providing complete data reduced the advantage to TCAs to a trend (P < 0.10). When
      the TCAs were grouped into those with dual action on 5-hydroxytryptamine (HT) and
      noradrenaline reuptake (clomipramine and amitriptyline) and those with
      predominantly noradrenaline reuptake (imipramine, desipramine and maprotiline),
      only the dual action TCAs had greater efficacy than SSRIs (effect size = -0.30,
      95% CI -0.54 to -0.05, P = 0.017). When TCAs were considered individually, only
      amitriptyline was significantly more effective than comparator SSRIs (effect size
      = -0.37, 95% CI -0.67 to -0.07, P = 0.015). More patients overall discontinued
      treatment on TCAs than on SSRIs (29.0% vs. 25.5%), although this did not reach
      statistical significance (RR = 0.88, 95% CI 0.75 to 1.03, P = 0.121). However,
      significantly more patients stopped treatment due to adverse effects on TCAs
      compared to SSRIs (14.2% vs. 9.1%, RR = 0.66, 95% CI 0.50 to 0.87, P = 0.003)
      with no difference in discontinuations due to treatment failure (10% vs. 11.6%,
      RR = 1.13, 95% CI 0.84 to 1.51, P = 0.42). This meta-analysis suggests that at
      least some TCAs may be more effective than SSRIs in depressed inpatients, with
      there being the strongest evidence for amitriptyline. A possible explanation is
      that this is related to a dual action in inhibiting both 5-HT and noradrenaline
      reuptake. In agreement with previous meta-analyses, TCAs appear less well
      tolerated than SSRIs, although the absolute risk difference for discontinuation
      due to adverse effects (4.9%, 95% CI -8.1 to -1.7%) is of uncertain clinical
      significance.

PMID- 9597347
TI  - Serotonin: and what about its side effects?
AB  - Many of the antidepressants introduced within the last decade have different and
      distinctive effects on neurotransmitter receptors, which delineate them from the
      older compounds. Clinically, these synaptic effects can be linked to therapeutic
      and certain adverse effects. Knowledge about these effects helps in understanding
      the advantages of newer compounds relative to the older compounds, and
      differences among new compounds in terms of their side effect profiles and
      certain drug interactions. Thus, the in vitro findings presented should help
      clinicians choose the most appropriate antidepressant for each patient and,
      potentially, will help to prevent or minimize the occurrence of certain side
      effects and drug interactions.

PMID- 9597348
TI  - Sexual dysfunction in depression: disease- or drug-related?

PMID- 9597350
TI  - Naturalistic conceptions of moral maturity.
AB  - By examining naturalistic conceptions of moral maturity, this project sought a
      more comprehensive understanding of moral excellence than is evident in dominant
      theories of moral development. Studies 1 and 2 involved different samples of 120
      adults (17-25, 35-55, and 65+ years). Study 3 involved a sample of 180
      undergraduates. In Study 1, a free-listing procedure was used to generate the
      attributes of a highly moral person as well as those for two related person
      concepts. In Study 2, a rating procedure for these attributes was used to
      generate a prototype of the moral person-concept. In Study 3, a similarity
      sorting task was used to uncover people's implicit typology of moral maturity.
      The findings indicate that naturalistic notions of moral excellence not only
      contain themes of principled reasoning but also reference aspects of moral
      character and virtue that enlarge our understanding of the psychological
      functioning of the mature moral agent.

PMID- 9597349
TI  - New antidepressants and the cytochrome P450 system: focus on venlafaxine,
      nefazodone, and mirtazapine.
AB  - OBJECTIVE: This review critically evaluates recent information on the cytochrome
      P450 system, with an emphasis on drug interactions involving antidepressant
      medications, particularly venlafaxine, nefazodone, and mirtazapine. METHODS:
      International literature on the cytochrome P450 system and related drug
      interactions from 1995-1997 were critically examined. RESULTS: Venlafaxine,
      nefazodone, and mirtazapine have different effects on the cytochrome P450 system.
      In vitro, venlafaxine is a weaker CYP2D6 inhibitor than most of the selective
      serotonin reuptake inhibitors (SSRIs) by a factor of 1-3 orders of magnitude. In
      vivo drug interaction studies generally confirm in vitro results. However, some
      exceptions exist. The clinical significance of such interactions remains unknown.
      Venlafaxine had minimal or no demonstratable inhibition of CYP1A2, CYP3A4, or
      CYP2C. Nefazodone is a potent inhibitor of CYP3A4 and is therefore absolutely
      contraindicated with concurrent administration of terfenadine, astemizole, and
      cisapride. It is a weak inhibitor of CYP1A2, 3A4, and 2D6. A metabolite of
      nefazodone, mCPP, is a weak and probably clinically insignificant inhibitor of
      CYP2D6. Mirtazapine has minimal inhibitory effects on CYP1A2, CYP3A4, and CYP2D6
      in vitro. Little is known about its interactions with other drugs. CONCLUSIONS:
      With the addition of the latest antidepressant medications, the clinician may now
      choose antidepressants with little liability for drug-drug interactions.
      Venlafaxine and mirtazapine are associated with a lower risk of clinically
      significant drug interactions than SSRIs. Nefazodone is a potent inhibitor of
      CYP3A4 and therefore may not be suitable for all patient populations. It is,
      however, a much weaker CYP2D6 inhibitor than the SSRIs. More studies are needed
      to assess more accurately and precisely the risk of such untoward drug-drug
      interactions with these novel antidepressants, particularly in more diverse
      ethnic patient populations.

PMID- 9597351
TI  - Can prototypes inform moral developmental theory?
AB  - L. J. Walker and R. C. Pitts (1998) suggest that research on prototypes of moral
      excellence can lead to important new insights for accounts of moral development
      that are unlikely to emerge from the efforts of theorists working within
      psychological or philosophical paradigms. In this commentary, I argue that (a)
      experts in philosophical and psychological paradigms can and do contribute to
      revisions of theories of moral excellence, and (b) the study of prototypes has
      limited value for resolving some important theoretical issues. Three research
      topics that can be informed by the investigation of prototypes of moral
      excellence are described.

PMID- 9597353
TI  - Infants' perception of object unity in translating and rotating displays.
AB  - In 3 experiments, the authors examined the sensitivity of infants to the unity of
      a partly occluded moving rod undergoing translation, rotation, or oscillation.
      Four-month-old infants were sensitive to the unity of the partly occluded rod
      when it translated, but not when it rotated, behind an occluder. Six-month-old
      infants perceived the rotating rod as continuing behind the occluder, but they
      did not perceive the unity of a rod that oscillated back and forth behind the
      occluder. Finally, 6-month-old infants showed an ambiguous response to a rotating
      rod when the shape of the occluder was changed from rectangular to round. These
      findings suggest that all types of common motion are not equivalent for
      specifying infants' perceptions of occluded objects. Additional factors should be
      considered that take into account the information specified by different types of
      motion and by different conditions at the intersection of the occluder and the
      object.

PMID- 9597355
TI  - Why do infants make A not B errors in a search task, yet show memory for the
      location of hidden objects in a nonsearch task?
AB  - In 4 experiments, infants aged 8 to 12 months were tested on A not B search
      tasks, and nonsearch A not B tasks following the violation-of-expectation
      paradigm. A 1-location task and 2 control tasks were also conducted. In the
      nonsearch tasks, a toy was hidden in A, moved to B, and retrieved after a delay
      from either A (impossible) or B (possible). Results showed significantly longer
      looking times at impossible events, indicating some memory for where the object
      was hidden and an expectation of where it should be found. This effect occurred
      at delays at which infants made the A not B error when searching, and at a longer
      delay of 15 s. The results showed clearly that infants have some memory for the
      object's location, even at delays at which they search at the incorrect location.
      Discussion centers on how these results are accounted for within explanations of
      the A not B error.

PMID- 9597354
TI  - Continuity in tactual-visual cross-modal transfer: infancy to 11 years.
AB  - The present study demonstrated that individual differences in cross-modal
      transfer showed continuity over a 10-year span. Tactual-visual tasks, requiring
      visual recognition of shapes that had previously been felt but not seen, were
      given to full-term and preterm children at 2 ages, 1 and 11 years. Cross-modal
      performance showed a left-hand advantage at 11 years and, for both groups, cross
      age correlations were significant when tactual exploration at 11 years was done
      with the left hand (r = .34-.36). The continuity showed some specificity in that
      the infant measure did not relate to other types of cross-modal performance at 11
      years and was not dependent on aspects of spatial ability involving form
      perception. This continuity accounted for most of the previously reported
      relation of infant cross-modal ability to 11-year IQ.

PMID- 9597356
TI  - Age, individuality, and context as factors in sustained visual attention during
      the preschool years.
AB  - In 3 studies, the authors explored age changes and individual differences in
      preschool children's sustained attention in several different contexts--watching
      a videotape, playing with toys, and performing reaction time tasks. Various
      indexes of attention increased from 30 months to 54 months, whereas inattention
      decreased. Changes tended to occur earlier for play and television viewing than
      for the reaction time task. Together, the results also provide evidence for
      individual differences in measures of attention and inattention through high
      internal consistency and stability over time within situations. Correlations
      across situations, however, were low to modest. These results suggest that
      children have stable tendencies to focus and sustain attention in particular
      contexts but that their attention varies with the demands of the task and their
      ability or interest in meeting those demands.

PMID- 9597358
TI  - Mother-child relationship, child fearfulness, and emerging attachment: a short
      term longitudinal study.
AB  - Mother-child relationship (maternal responsiveness and shared affective
      positivity), observed in naturalistic interactions, and child fearfulness,
      assessed in standard procedures involving exposure to unfamiliar stimuli and with
      parental reports, were examined at 8-10 and 13-15 months in relation to child
      attachment in the Strange Situation at 13-15 months (N = 108). Mother-child
      relationship, at 13-15 months only, predicted child security versus insecurity
      but not the type of insecurity. In contrast, child fearfulness was unrelated to
      security versus insecurity but predicted the type of insecurity and arousal in
      the Strange Situation. Resistant and highly aroused children (B3-C2) were more
      fearful than avoidant and less aroused children (A1-B2). The analyses using
      discrete and continuous attachment scores produced converging results. The study
      informs the debate on early relationships, temperament, and attachment.

PMID- 9597357
TI  - Parenting goals as organizers of responses to parent-child disagreement.
AB  - Parenting goals are outcomes that parents hope to achieve during interactions
      with children. Three studies involving 138 men (78 fathers) and 158 women (110
      mothers) examined the causes and consequences of parents' focusing on various
      goals during disagreements with young children. Women were more likely than men
      to focus on relationship-centered (RC) goals, public situations increased concern
      for short-term parent-centered (PC) goals, and empathy was predictive of long
      term child-centered (CC) and RC goals. PC goals were associated with power
      assertion, CC goals with reasoning, and RC goals with warm, negotiating, and
      cooperative parenting behavior. Attributions of intentionality and dispositional
      causation were possible mediators of the link between power assertion and PC and
      CC goals. Instructions to focus on PC goals increased negative affective states
      and decreased sympathy for children, whereas instructions to focus on RC goals
      had the opposite effects.

PMID- 9597359
TI  - Metarepresentation in action: 3-, 4-, and 5-year-olds' developing theories of
      mind in parent-child conversations.
AB  - Using a cross-sectional natural language database, the authors investigated the
      parent-child conversations of 36 three-, 4-, and 5-year-olds to explore 2 issues
      regarding the development of metarepresentation. First, children's uses of
      explicit contrastives (ECs)--utterances that explicitly contrast 2 differing
      mental states--were explored. Four-year-olds and, to a greater extent, 5-year
      olds were found to reliably use ECs. Second, parents' responses to children's
      uses of "I don't know" and implicit contrastives (e.g., contradictions) were
      examined to determine whether parents took these opportunities to highlight the
      representational nature of mental states. All children regularly elicited
      mentalistic responses from their parents and, in some cases, these parental
      responses were positively related to children's production of mental talk.
      Findings are discussed in terms of how theory of mind development may be guided
      by scaffolding processes.

PMID- 9597360
TI  - Preschoolers' use of desires to solve theory of mind problems in a pretense
      context.
AB  - K. Bartsch and H. M. Wellman (1995) have suggested that 3-year-old children's
      preference to construe behavior in terms of desire may interfere with their
      ability to reason according to belief in standard false belief tasks. Other
      researchers have suggested that young children fail typical measures of theory of
      mind because they have a reality bias (e.g., P. Mitchell, 1994). Study 1
      demonstrates that even young children are able to correctly attribute a false
      belief to an agent when that belief is about the status of a pretense. Study 2
      shows that children find it easier to attribute a false belief when the desires
      of the agent are eliminated. However, Study 3 suggests that a reality bias also
      influences children's ability to consider beliefs. Implications for recent
      accounts of theory of mind development are discussed.

PMID- 9597361
TI  - Developing organization of mental verbs and theory of mind in middle childhood:
      evidence from extensions.
AB  - The purpose of the study was to assess developments in the theory of mind
      suggested by changes in the organization of cognitive verb extensions during the
      elementary school years. Adults and 3rd- and 5th-grade children were provided
      with a set of mental activity scenarios and were asked to select the best verbs
      from a list of cognitive verbs that might apply to each scenario. Changes in
      organization were assessed by examining overlapping uses of cognitive verbs in
      different contexts. There were 3 major changes with development: (a) the
      understanding of the role of memory in input functions increased, (b) the
      interrelatedness of memory- and comprehension-related verbs increased, and (c)
      the importance of cognitive certainty and uncertainty engaged by constructive
      processing verbs increased. Together, these findings suggest that a
      constructivist theory of mind develops in later childhood.

PMID- 9597362
TI  - Children's use of triadic eye gaze information for "mind reading".
AB  - Five experiments examined children's use of eye gaze information for "mind
      reading" purposes, specifically, for inferring another person's desire. When
      presented with static displays in the first 3 experiments, only by 4 years of age
      did children use another person's eye direction to infer desires, although
      younger children could identify the person's focus of attention. Further, 3-year
      olds were capable of inferring desire from other nonverbal cues, such as pointing
      (Experiment 3). When eye gaze was presented dynamically with several other
      scaffolding cues (Experiment 4), 2- and 3-year-olds successfully used eye gaze
      for desire inference. Scaffolding cues were removed in Experiment 5, and 2- and 3
      year-olds still performed above chance in using eye gaze. Results suggest that 2
      year-olds are capable of using eye gaze alone to infer about another's desire.
      The authors propose that the acquisition of the ability to use attentional cues
      to infer another's mental state may involve both an association process and a
      differentiation process.

PMID- 9597363
TI  - Maternal drug use during pregnancy: are preterm and full-term infants affected
      differently?
AB  - This study examined whether preterm infants are more vulnerable to the effects of
      prenatal drug exposure than are full-term infants. The sample of 235 low-income
      African American mothers and their infants included 119 cocaine-polydrug users,
      19 alcohol-only users, and 97 nonusers; 148 infants were full term and 87 were
      preterm. Direct effects of exposure on birth weight, birth length, ponderal
      index, and irritability were moderated by length of gestation: Fetal growth
      deficits were more extreme in later-born infants, whereas increases in
      irritability were more extreme in earlier born infants. Effects of exposure on
      cardiorespiratory reactivity to a neonatal exam were not moderated by length of
      gestation. In general, effects of exposure occurred for both cocaine-polydrug and
      alcohol only users and so could not be unambiguously attributed to either of
      these drugs alone.

PMID- 9597364
TI  - Arousal modulation in cocaine-exposed infants.
AB  - The ability to modulate arousal is a critical skill with wide-ranging
      implications for development. In this study, the authors examined arousal
      regulation as a function of levels of prenatal cocaine exposure in 107 infants at
      4 months of age using a "still-face" procedure. Facial expressions were coded. A
      greater percentage of heavily cocaine-exposed infants, compared with those who
      were unexposed to cocaine, showed less enjoyment during en face play with their
      mothers and continued to show negative expressions during the resumption of play
      following a period when the interaction was interrupted. This finding was
      independent of other substance exposure, neonatal medical condition,
      environmental risk, maternal contingent responsivity, and concurrent maternal
      sensitivity and vocalizations.

PMID- 9597365
TI  - Cognitive functioning in 8- to 18-month-old drug-exposed infants.
AB  - This study examined the cognitive functioning in 236 infants at 8 and 18 months
      of age. Thirty-seven infants were heavily exposed to cocaine in-utero, 30 were
      lightly exposed, and 169 were not exposed to cocaine. Cognitive functioning was
      evaluated with the Bayley Scales of Infant Development (2nd ed.; N. Bayley, 1993)
      at both ages. Infant information processing was also assessed with an infant
      controlled habituation procedure. Results indicated that (a) infants of cocaine
      abusing women had higher neonatal medical and environmental risk scores; (b) at 8
      months, exposure groups did not differ in Psychomotor Development Index, Mental
      Development Index (MDI) scores, or recovery to a novel stimulus; and (c) infants
      heavily exposed to cocaine or high environmental risk had a decrease in MDI
      scores from 8 to 18 months. These results were obtained when neonatal medical and
      environmental risk, as well as polydrug exposure, were controlled.

PMID- 9597366
TI  - The development of bases for trait attribution: children's understanding of
      traits as causal mechanisms based on desire.
AB  - Two studies investigated 4- to 7-year-old children's understanding that traits
      can be causal mechanisms based on desires, as well as mere summaries of
      behavioral regularities. In Experiment 1, children made predictions given trait
      information. Children from 5 years made different emotion predictions about the
      same situation for actors with different traits, thus appreciating traits as
      psychological causes. For behavior prediction, children over age 4 generalized
      across situations. In Experiment 2, accurate emotion prediction by 3- to 7-year
      olds was linked to understanding desire as a subjective mental property. The
      results suggest that children change from viewing traits as behavioral
      regularities to understanding them as internal mediators, and that advances in
      understanding desire underlie this change. These changes in understanding traits
      extend research on theory of mind beyond the basic concepts of desire and belief.

PMID- 9597367
TI  - Self-blame and peer victimization in middle school: an attributional analysis.
AB  - Relations between characterological versus behavioral self-blaming attributions
      for victimization and maladjustment were examined in middle school students.
      Respondents completed a questionnaire that assessed self-perceptions of victim
      status, attributions for hypothetical incidents of victimization, and feelings of
      loneliness, social anxiety, and low self-worth. They also completed peer
      nomination procedures measuring perceptions of victimization in others, as well
      as peer acceptance and rejection. Self-perceived victimization was associated
      with characterological self-blame, loneliness, anxiety, and low self-worth. Peer
      perceived victimization, in contrast, was related to acceptance and rejection.
      The data suggest that self-views are more predictive of the intrapersonal
      consequences of victimization (loneliness, anxiety, low self-worth), whereas peer
      views are more predictive of interpersonal consequences (peer acceptance and
      rejection).

PMID- 9597368
TI  - Hypoglycemic and hypotensive effects of 6-cyclohexyl-2'-O-methyl-adenosine, an
      adenosine A1 receptor agonist, in spontaneously hypertensive rat complicated with
      hyperglycemia.
AB  - Metabolic and cardiovascular effects of 6-cyclohexyl-2'-O-methyl-adenosine (SDZ
      WAG 994), a selective and orally-active adenosine A1 receptor agonist, were
      examined in spontaneously hypertensive rats (SHR) with hyperglycemia (SHR-DM).
      This model was made by the administration of streptozotocin (STZ; 60 mg/kg s.c.)
      to SHR 2 days after their birth. The serum glucose concentration and
      systolic/mean blood pressures (MBP) in 18-22-week-old rats were 14.7 +/- 0.8
      mmol/1 and 153 +/- 3/124 +/- 3 mmHg in SHR-DM, 13.7 +/- 0.3 mmol/1 and 123 +/-
      3/96 +/- 4 mmHg in normotensive with STZ (WKY-DM), 10.3 +/- 0.3 mmol/1 and 165 +/
      1/136 +/- 3 mmHg in non-treated (without STZ) SHR, and 10.0 +/- 0.3 mmol/1 and
      115 +/- 3/90 +/- 4 mmHg in non-treated WKY, SDZ WAG 994 at 0.1 mg/kg p.o. lowered
      the serum glucose concentration, blood pressure and heart rate in SHR-DM. The
      effects were associated with the decrease in free fatty acid (FFA), triglyceride
      (TG), phospholipid (PL) and total cholesterol (TC) in serum of both SHR-DM and
      WKY-DM. On the contrary, the hypoglycemic effect was not found in WKY-DM,
      although the hypotensive effect was still observed. These data suggest that the
      risk factors for metabolic and cardiovascular complications in diabetes are
      reduced by SDZ WAG 994 through activation of adenosine A1 receptors in adipocyte.

PMID- 9597369
TI  - The incidence of nephropathy in type 1 diabetic patients with proliferative
      retinopathy: a 10-year follow-up study.
AB  - Patients with type 1 diabetes mellitus and with proliferative retinopathy often
      have a concomitant diabetic nephropathy. However, in cross-sectional studies it
      has been shown that 35% of patients with proliferative retinopathy do not show
      signs of diabetic nephropathy. The aim of the present study was to examine the
      incidence of diabetic nephropathy in type 1 diabetic patients with proliferative
      retinopathy but without signs of nephropathy. To that end, out of 102 consecutive
      patients with proliferative retinopathy attending the University Hospital, Lund,
      in 1986, 24 patients did not show any clinical signs of nephropathy, and were
      followed for 10 years regarding the development of nephropathy. Their age was
      36.7 +/- 9.8 years, age at onset 11.8 +/- 7.5 years, diabetes duration 25.7 +/-
      6.9 years and duration of proliferative retinopathy 4.6 +/- 3.8 years (mean +/-
      S.D.). At entry, no patient had albuminuria (< 30 mg/l), and albumin creatinine
      clearance ratio was < 0.01 x 10(-3). During the 10-year follow-up period, two of
      the patients showed isolated higher peaks of elevated urinary albumin, but none
      of the 24 patients developed persistent microalbuminuria (> or = 30 mg/l). Two
      patients died before follow-up, but none of these had developed microalbuminuria
      at the time for death. Based on mean annual measurements, there were no increases
      in HbA1c, systolic and diastolic blood pressure, and serum creatinine levels. At
      entry, seven of the patients were treated with antihypertensive drugs and another
      three patients received such treatment during the study period. In conclusion, in
      a subgroup of patients with proliferative retinopathy, i.e. without clinical
      signs of diabetic nephropathy, no patient developed persistent microalbuminuria
      during a 10-year follow-up period. These results indicate further evidence for at
      least partly different pathogenic mechanisms behind diabetic retinopathy and
      nephropathy.

PMID- 9597371
TI  - Factors influencing preference of insulin regimen in people with type 1 (insulin
      dependent) diabetes.
AB  - The two commonest insulin regimens in current use in the UK are twice daily
      administration of short- and intermediate-acting insulins in combination, and
      soluble insulin before meals with intermediate-acting insulin at bed-time (basal
      bolus regimen). A cross-sectional sample of patients with type 1 diabetes was
      studied using either a twice daily insulin regimen (n = 30) or a basal-bolus
      regimen (n = 30), to assess their satisfaction with choice of insulin regimen and
      to examine the relationships between type of insulin regimen, personality,
      demographic variables and glycaemic control. Patients treated with a basal-bolus
      insulin regimen tended to be younger (P = 0.07), had an earlier onset of type 1
      diabetes (P = 0.04), adjusted their dose of insulin more frequently (P = 0.01),
      had received more secondary and further education (P = 0.03), belonged to a
      higher socio-economic class, tended to be unmarried (P = 0.07) and were less
      likely to be smokers (P = 0.03), than the group treated with twice daily
      administration of insulin. Current and previous glycaemic control assessed by
      glycated haemoglobin concentration, showed no correlation with type of insulin
      regimen, demographic data or personality variables.

PMID- 9597370
TI  - Hypoglycemic action of an oral fig-leaf decoction in type-I diabetic patients.
AB  - The effect of a decoction of fig leaves (Ficus carica), as a supplement to
      breakfast, on diabetes control was studied in insulin-dependent diabetes mellitus
      (IDDM) patients (six men, four women, age 22-38 years, body mass index (BMI):
      20.8 +/- 3.0 kg/m2, HbA1c 7.6 +/- 0.9% with a mean duration of diabetes of 9 +/-
      6.3 years). The patients were managed with their usual diabetes diet and their
      twice-daily insulin injection. During the first month, patients were given a
      decoction of fig leaves (FC) and during the next month a non-sweet commercial tea
      (TC). The patients were divided into two groups (n = 5) with random allocation
      and cross-over design. A standard breakfast was given at the beginning and end of
      each month-run. C-peptide, 2 h pre- and post-prandial glycemia, HbA1c,
      cholesterol, lipid fractions and hematology data, were analyzed during each
      visit. Glycemic profiles (7/day per week) were recorded by patients. Only two
      patients had intolerance dropout. Post-prandial glycemia was significantly lower
      during supplementation with FC 156.6 +/- 75.9 mg/dl versus TC 293.7 +/- 45.0
      mg/dl (P < 0.001) without pre-prandial differences 145.0 +/- 41.5 and 196.6 +/-
      43.2 mg/dl, respectively. Medium average capillary profiles were also lower in
      the two sub-groups of patients during FC 166.7 +/- 23.6 mg/dl, P < 0.05 and 157.1
      +/- 17.0 mg/dl versus TC 245.8 +/- 14.2 mg/dl and 221.4 +/- 27.3 mg/dl. Average
      insulin dose was 12% lower during FC in the total group. The addition of FC to
      diet in IDDM could be of help to control postprandial glycemia.

PMID- 9597372
TI  - An IDDM patient who complained of chest oppression with ischemic changes on ECG
      in insulin-induced hypoglycemia.
AB  - A 34-year-old female IDDM patient complained of chest oppression in hypoglycemic
      episodes and electrocardiograms revealed reversible ischemic changes occurring
      concomitantly with hypoglycemia. The ECG changes improved and the chest
      oppression disappeared following increasing blood glucose level by glucose
      intake. Master's double load test and treadmill load test were positive for
      ischemic changes. Radioisotopic myocardial scintigraphy by thallium and BMIPP did
      not show any filling defects and coronary angiography revealed no remarked
      stenosis in the coronary arteries. She had no mitochondrial tRNA(Leu) (A-->G)
      gene mutation at nucleotide position 3243, but both the patient and her mother
      had a G-to-A transition within the replication origin of the light strand at
      nucleotide position 5744 of the mitochondrial gene. As the patient's maternal
      family had no history of ischemic heart disease, it is not clear whether
      mitochondrial gene mutation at nucleotide position 5744 reflects the occurrence
      of cardiac ischemia. Some disorders of microcirculation in capillary vessels in
      cardiac muscles may occur in such patients.

PMID- 9597373
TI  - Initial urinary albumin excretion determines the progression of microalbuminuria
      in patients with type-2 diabetes and normotensive blood pressure values despite
      improved metabolic control.
AB  - Persistent increased urinary albumin excretion rate (UAER) is associated with
      increased cardiovascular mortality in type-2 diabetes, however, there are no
      conclusive data about the progression of advanced UAER in these patients. The
      present study has investigated the effect of metabolic intervention on the
      progression in UAER in relation to initial UAER levels. A total of 20 patients
      with type-2 diabetes and secondary failure to sulfonylurea were observed during 1
      year (age, 60 +/- 8 years; HbA1c, 10.8 +/- 1.4%; and duration of diabetes, 17 +/-
      10 years) and divided into two groups: group 1 (n = 10; UAER: 51 +/- 35 mg/24 h);
      and group 2 (n = 10; UAER: 191 +/- 175 mg/24 h). Despite a significant
      improvement of metabolic control by insulin treatment in both groups (HbA1c:
      group 1: 11 +/- 1.5 vs. 7.9 +/- 1.2%; group 2: 10.6 +/- 0.9 vs. 9.1 +/- 1.3%, P <
      0.001), a progression of UAER was observed in group 2 (191 +/- 175 vs. 331 +/-
      237 mg/24 h, P < 0.02), but not in group 1 (51 +/- 35 vs. 41 +/- 24 mg/24 h).
      Still serum creatinine levels remained normal in all patients during the
      observation period. The 24 h blood pressure (RR) values in the two groups
      remained normal under antihypertensive therapy throughout the study (group 1: RR
      syst: 130 vs. 136 mmHg; RR diast: 80 vs. 81 mmHg, mean arterial pressure (MAD):
      89 vs. 93 mmHg; group 2: RR syst: 139 vs. 134 mmHg; RR diast: 78 vs. 75 mmHg,
      MAD: 97 vs. 90 mmHg). The data shows that in type-2 diabetic patients with
      normotensive blood pressure values the initial urinary albumin excretion levels
      determine the progression of UAER. When metabolic control is improved incipient
      UAER remains constant, but advanced UAER shows progression.

PMID- 9597374
TI  - Evidence for dissociation of insulin- and weight-reducing effects of metformin in
      non-diabetic male patients with coronary heart disease.
AB  - Metformin effects on insulin resistance and insulin/glucose relationships during
      an oral glucose tolerance test (OGTT) were investigated in 60 non-diabetic male
      patients previously treated with coronary artery bypass surgery or angioplasty in
      an open, 12 week prospective study. During a 4 week run-in period, all patients
      were treated with diet and lifestyle advice and lovastatin 40 mg daily.
      Lovastatin treatment was continued in all the patient throughout the study. After
      randomization, the metformin group got additional treatment with metformin up to
      2000 mg/day. Fasting plasma glucose levels and glucose area during OGTT remained
      unaffected by metformin treatment. Insulin resistance, assessed as the insulin
      area/glucose area ratio during OGTT decreased by 24% (P = 0.028) in the whole
      group and by 30% in obese subjects (P = 0.049). Notably, the reduction in body
      weight by metformin treatment did not correlate with amelioration of insulin
      resistance or changes in lipid levels. However, changes in insulin resistance
      correlated with changes in lipid levels. Hence, metformin effects on insulin
      resistance and body weight appear to be mediated, at least partly, by different
      mechanisms, while metformin effects on insulin resistance and lipid metabolism
      are associated in non-diabetic subjects.

PMID- 9597375
TI  - Does peripheral neuropathy invariably accompany nephropathy in type 1 diabetes
      mellitus?
AB  - In patients with Type 1 diabetes mellitus complicated by diabetic nephropathy and
      retinopathy, it is usually believed that significant neuropathy is almost
      universal, but few studies have directly addressed this. This study assessed
      neuropathy in 91 such subjects, using vibration perception thresholds (VPT) and
      the neuropathy disability score (NDS). A total of 34% of subjects had no
      neuropathy on age adjusted VPT (z score) and 26% had no neuropathy on NDS. The
      severity of neuropathy as measured by VPT z score was related to increasing
      glycated haemoglobin (P = 0.02) and male sex (P = 0.03), and NDS was
      independently associated with age (P < 0.0001) and HbA1c (P = 0.003). These
      factors together accounted for only 12 and 31% of the total variance in VPT z
      score and NDS, respectively. In conclusion, the study has shown that a
      significant proportion of patients with diabetic nephropathy are free of
      neuropathy, but the full explanation for their protection from neuropathy is
      unclear.

PMID- 9597376
TI  - Hospital discharges for diabetic foot disease in New Zealand: 1980-1993.
AB  - The aim of this study was to determine the prevalence of hospital discharges for
      diabetic foot disease from 1980 to 1993 in New Zealand and identify regional
      variations. Data from the International Classification of Disease (ICD) discharge
      codes for diabetes and its complications from 1980 to 1993 were reviewed for
      diabetic foot disease. The total number of discharges/100,000 total population
      has increased from 13.56 in 1980 to 25.79 in 1993. The age and sex-standardised
      total bed/days per 1000 total population increased from 5.02 in 1980 to 5.85 in
      1993. The total inpatient cost for the management of diabetic foot disease in New
      Zealand (population 3.3 million) for 1993 is estimated to be in the region of
      NZ$10-11 million (USD$7-7.7 million), indicating the need to put strategies in
      place to manage this problem. Strategies that reduce the individual and inpatient
      burden of this advanced stage complication of diabetes mellitus can be
      implemented easily for a relatively modest cost.

PMID- 9597377
TI  - Glucose tolerance and mortality in an elderly Finnish population.
AB  - The aim of this study was to describe the association between glucose tolerance
      status and mortality in an elderly (> 70 years) Finnish community-living
      population (n = 379, of whom 141 were men). The baseline examination in 1991-1992
      consisted of a postal questionnaire, a physical examination, and a 2-h oral
      glucose tolerance test. The follow-up was continued until death or 31 May 1996.
      The deaths were ascertained from official death certificates; 31% (n = 44) of the
      men and 18% (n = 40) of the women died within 4 years. The cumulative 4-year
      mortalities were 42% in previously diagnosed diabetic men, 25% in previously
      undiagnosed diabetic men, 27% in men with impaired glucose tolerance (IGT), and
      31% in men with normal glucose tolerance (NGT). The corresponding figures for
      women were: 26%, 29%, 19%, and 8%, respectively. After adjusting for age, gender,
      smoking, body mass index and exercise by the Cox proportional hazards model in
      the total population, the estimated relative mortality rate was 2.2 (95%
      confidence interval (CI) 1.2 to 4.1) in previously diagnosed diabetic subjects,
      1.7 (95% CI 0.8 to 3.7) in subjects with previously undiagnosed diabetes, and 1.2
      (95% CI 0.7 to 2.1) in the IGT group, respectively, all in comparison to the NGT
      subjects. In separate modelling by gender these relative mortalities were higher
      in women than in men, but the gender difference could well be explained by chance
      variation. In conclusion, the results suggest that previously diagnosed diabetes
      is associated with increased mortality among the elderly and, particularly among
      elderly women, undiagnosed diabetes and even IGT may be associated with increased
      mortality.

PMID- 9597379
TI  - Skin lesions in diabetes mellitus: prevalence and clinical correlations.
AB  - With the aim to assess the prevalence and the main clinical correlations of skin
      lesions in diabetes mellitus, 457 diabetic subjects consecutively attending an
      outpatient clinic underwent a dermatological examination. Neurovascular foot
      lesions were excluded. Thirty-five of 64 IDDM patients (54%) had skin alterations
      mainly consisting of vitiligo (9% of all patients), psoriasis (9%) and eczema
      (8%). The most frequent skin lesions observed in 240/393 NIDDM subjects (61%)
      were represented by infections (20% of all patients) and diabetic dermopathy
      (12.5%), while other lesions were not common. NIDDM patients with skin infections
      had a worse metabolic control, and those with diabetic dermopathy had a greater
      prevalence of neuropathy and large vessel disease than patients without skin
      lesions. These data show that the prevalence of skin diseases in a large,
      unselected diabetic population is higher than expected and indicate that, in most
      cases, a careful dermatological examination and a better metabolic control are
      needed in order to improve quality of life in these patients.

PMID- 9597378
TI  - Relationship of elevated urinary albumin excretion to components of the metabolic
      syndrome in non-insulin-dependent diabetes mellitus.
AB  - Microalbuminuria is associated with increased morbidity and early mortality in
      non-insulin-dependent diabetes mellitus (NIDDM), mostly due to cardiovascular
      disease. This association may be due to a higher prevalence of known
      cardiovascular risk factors in those with microalbuminuria. We examined the
      relationship of microalbuminuria to components of the metabolic syndrome in 98
      NIDDM patients with elevated urinary albumin excretion rate (UAER) (> 10.5
      micrograms/min) (high UAER) and 102 normoalbuminuric NIDDM patients. Patients
      with high UAER were older than normoalbuminuric patients (P < 0.05), but they did
      not differ with respect to duration of diabetes, total cholesterol, body mass
      index (BMI) or the prevalence of smoking. A total of 58 (60%) patients with
      elevated UAER had two or more of hypertension, ischaemic heart disease (IHD),
      hypertriglyceridaemia and obesity compared with 41 (40%) in the normoalbuminuric
      group, (P < 0.05). Only nine (9.2%) high UAER patients had none of the above risk
      factors compared with 26 (25.5%) in the normoalbuminuric group (P < 0.01). The
      prevalence of hypertension (blood pressure (BP) > 160/95) was significantly
      higher in high UAER patients; 61/98 (62%) versus 39/102 (38%) in normoalbuminuric
      group, (P < 0.05). Elevated UAER was also associated with a higher risk of
      macrovascular disease (P < 0.01). The high UAER group included 50 Caucasian, 30
      Asian and 18 Afro-Caribbean. The three groups did not differ with respect to
      total cholesterol, glycosylated haemoglobin (HbA1c) or prevalence of smoking.
      Asians had a lower BMI, a lower BP and a lower prevalence of peripheral vascular
      disease (PVD), but had a higher serum triglyceride (P < 0.01 for all) compared
      with Caucasian. Patients of Afro-Caribbean origin had a lower prevalence of IHD
      (0%) compared with both Asians (16%) and Caucasians (22%). Elevated UAER in NIDDM
      is closely associated with components of the metabolic syndrome and an increased
      risk of IHD and PVD. There are however, significant ethnic differences in this
      association.

PMID- 9597380
TI  - Non-insulin-mediated glucose uptake in several insulin-resistant states in the
      postabsortive period.
AB  - The aim of our work was to study non-insulin-mediated glucose uptake (NIMGU), in
      the postabsorptive state, in several pathologies characterized by peripheral
      insulin resistance, namely, obesity (n = 10), NIDDM (n = 7), acromegaly (n = 7)
      and Cushing's disease (n = 6). These groups were compared with a group of 16
      healthy subjects. To estimate peripheral insulin sensitivity (SI) and glucose
      effectiveness (SG), we used the minimal model of glucose metabolism. Although all
      of these pathologies showed severe insulin resistance (control: 6.44 +/- 2.63,
      obesity: 2.84 +/- 1.57, NIDDM: 1.71 +/- 0.77, acromegaly: 1.88 +/- 1.23,
      Cushing's disease: 1.87 +/- 0.66 x 10(-4) min-1 (microU/ml)-1, P < 0.01), fasting
      insulin-mediated glucose uptake (IMGU) did not differ significantly among the
      five groups, because reactive hyperinsulinaemia was present in all of these
      states. The contribution of NIMGU to whole-body glucose uptake did not differ
      significantly among the five groups (control: 77 +/- 8%; obesity: 77 +/- 9%;
      acromegaly: 82 +/- 8%; Cushing's disease: 83 +/- 8%; NIDDM: 84 +/- 7%). In
      conclusion, our data show that, in the postabsorptive period, non-insulin
      mediated glucose uptake is a major determinant of glucose disposal and is similar
      in the different pathologies studied; on the other hand, although absolute rates
      of basal insulin-mediated glucose uptake are reduced in insulin-resistant states,
      they did not achieve statistical value compared with control subjects because of
      compensatory hyperinsulinaemia.

PMID- 9597381
TI  - Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy:
      a long-term study.
AB  - Forty-six diabetic patients with chronic painful peripheral neuropathy were
      treated with acupuncture analgesia to determine its efficacy and long-term
      effectiveness. Twenty-nine (63%) patients were already on standard medical
      treatment for painful neuropathy. Patients initially received up to six courses
      of classical acupuncture analgesia over a period of 10 weeks, using traditional
      Chinese Medicine acupuncture points. Forty-four patients completed the study with
      34 (77%) showing significant improvement in their primary and/or secondary
      symptoms (P < 0.01). These patients were followed up for a period of 18-52 weeks
      with 67% were able to stop or reduce their medications significantly. During the
      follow-up period only eight (24%) patients required further acupuncture
      treatment. Although 34 (77%) patients noted significant improvement in their
      symptoms, only seven (21%) noted that their symptoms cleared completely. All the
      patients but one finished the full course of acupuncture treatment without
      reported or observed side effects. There were no significant changes either in
      the peripheral neurological examination scores, VPT or in HbA1c during the course
      of treatment. These data suggest that acupuncture is a safe and effective therapy
      for the long-term management of painful diabetic neuropathy, although its
      mechanism of action remains speculative.

PMID- 9597382
TI  - Unusual infections in diabetes.
AB  - Infection with rare organisms or at unusual sites occur more frequently in people
      with diabetes. If not recognised and treated promptly, morbidity and mortality
      are high in such cases. Here we report cases of necrotising fascitis, malignant
      otitis externa, Fournier's gangrene and psoas abscess occurring in diabetics that
      needed intensive treatment with antibiotics, surgical debridement and insulin.
      Literature reviews suggest that cellular defence mechanisms may be impaired in
      people with diabetes.

PMID- 9597383
TI  - Minimal model of glucose metabolism: modified equations and its application in
      the study of insulin sensitivity in obese subjects.
AB  - As implemented in their program MINMOD, some of the parameters and variables of
      the equations representing Bergman and coworkers' minimal model of glucose
      metabolism have no simple rational relationship with the kinetic constants and
      constants of proportionality of the minimal model as such. In this work we
      implemented the original version of the minimal model, which does not suffer from
      this problem, and used it to investigate the source of insulin resistance among
      obese but otherwise healthy subjects. A fasting sampled intravenous glucose
      tolerance (FSIGT) test was performed in 38 healthy subjects of varying degrees of
      obesity (standard FSIGT test in 21 and tolbutamide FSIGT test in 17 subjects) in
      order to compare MINMOD and 'modified' equations (MI). Insulin sensitivity index
      (SI) in obese subjects was significantly lower than in lean subjects (4.58 +/-
      3.5 vs. 11.7 +/- 4.3. 10(-5) min-1 (pmol.l-1)-1, P < 0.0001). The lower SI in
      obese subjects was a consequence P3 parameter (0.178 +/- 0.08 vs. 0.440 +/-
      0.26.10(-5) min-2 (pmol.l-1)-1, P < 0.01), being p2 similar between obese and
      lean subjects (0.389 +/- 0.19 vs. 0.376 +/- 0.19.10(-1) min-1, NS). SI index
      correlated with p3 (r = 0.73, P < 0.0001), but not with p2 (r = 0.01, NS). Using
      these results and assuming that interstitial insulin is higher in obese subjects
      than in lean subjects, we have demonstrated that the proportionality constants of
      the model (k4 and k6) were lower in obese subjects than in lean subjects, but not
      the rate constant for insulin transfer across capillaries, k2. Our results
      suggest that the modified equations are a better theoretical approach to the
      minimal model method; and that low insulin sensitivity in obese subjects is due
      to receptor and/or post-receptor events rather than to slow transfer of insulin
      across capillary endothelium into the interstitial space.

PMID- 9597384
TI  - Helicobacter pylori infection and insulin-dependent diabetes mellitus.
AB  - Helicobacter pylori is associated with different diseases: duodenal ulcer,
      rosacea, ischaemic heart disease and gastric cancer. Given the abnormal
      immunological response and the high prevalence of gastrointestinal symptoms in
      diabetic patients, we conducted a study on H. pylori prevalence among these
      patients. We designed a case control study of a population-based cohort. Eighty
      insulin-dependent diabetes mellitus (IDDM) patients with an average age (24.05 +/
      8.3 years), and 100 control subjects (25 +/- 7.1 years) were selected to verify
      the seroprevalence of Helicobacter pylori in these populations. One serum sample
      was obtained from each subject for evaluation of antibodies against Helicobacter
      pylori, parietal cells (APA) and pancreatic islets cells (ICA). The
      seroprevalence of H. pylori among IDDM patients aged less than 24 years was
      significantly higher than among control subjects; the corresponding rate among
      IDDM aged greater than 24 years was significantly lower than among control
      subjects. Antibodies against parietal cells (APA) and islet cells (ICA) among H.
      pylori positive diabetic patients were significantly higher than among H. pylori
      negative diabetic patients. IDDM patients were subdivided on the basis of the
      evolutive course of diabetes. Seroprevalence of H. pylori as well as prevalence
      of ICAs decreased with IDDM duration. Nevertheless, no variation in the
      prevalence of APAs during the course of diabetes was observed. We observed an
      association between the seroprevalence of Helicobacter pylori and the duration of
      IDDM. The seroprevalence of H. pylori and ICA decreased with the evolutive course
      of diabetes mellitus among IDDM. The prevalence of ICA and APA in IDDM H. pylori
      positive subjects was higher than among controls.

PMID- 9597385
TI  - Blood pressure and coronary heart disease in NIDDM subjects at diagnosis:
      prevalence and risks in a Bangladeshi population.
AB  - Overall obesity and central fat distribution are frequently accompanied by
      hyperglycemia, hypertension (HTN) and coronary heart disease (CHD) observed in
      developed nations and in South Asian migrants. This study attempts to estimate
      the prevalence of CHD and HTN and to assess the related risks among the newly
      diagnosed diabetics in the developing communities. From a total of 3583 non
      insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT)
      subjects, the authors investigated 693 (M = 295, F = 398) randomly selected non
      smokers of age 30-60 years. WHO diagnostic criteria were used for NIDDM and IGT.
      Systolic and diastolic hypertension (sHTN and dHTN) were defined as systolic
      blood pressure (SBP) > or = 140 and diastolic (DBP) > or = 90 mmHg. Diagnosis of
      CHD was based on electrocardiogram either on rest or on stress or both when
      equivocal. The overall prevalence of CHD in the NIDDM subjects was 18.6%. The
      prevalence rates of sHTN and dHTN were 23.2 and 13.6%, respectively. CHD and HTN
      did not differ significantly between male and female and between urban and rural
      subjects. CHD prevalence was significantly higher in the higher tertiles of age,
      SBP and DBP (P < 0.001, for all cases). Logistic regression showed that only the
      increasing age, high waist-to-hip ratio (WHR) and high BP were the independent
      risks for CHD. For sHTN, the independent risks were increased age and high body
      mass index (BMI) (kg/m2). Regardless of sex and area, increased prevalence of CHD
      and HTN were found in the newly diagnosed diabetic subjects. Increased age,
      central obesity and HTN were the independent risks for CHD while advancing age
      and overall obesity was related to sHTN.

PMID- 9597386
TI  - Diabetes and it's complications in a Swedish county.
AB  - A cross-sectional survey with the aim to study the prevalence of diabetes and
      long-term complications was carried out in a health care district in Sweden with
      125,500 inhabitants. Information was extracted from the medical records. 4127
      people with diabetes were identified of whom 87% were classified as NIDDM (non
      insulin-dependent diabetes mellitus), 12% as IDDM (insulin-dependent diabetes
      mellitus) and 0.7% as secondary or unclassified diabetes. The prevalence of
      diagnosed diabetes was 3.3%. A total of 83% received their regular routine care
      at primary health care centres, 31% were treated with diet only, 36% had oral
      hypoglycaemic agents, 31% had insulin and 2% had combination therapy. The mean
      HbA1c was 7.2% (ref. range 4.0-5.3%). Of the adults (> 18 years) 27% had
      retinopathy, 13% had nephropathy and 27% had loss of pallaesthesia. 50% had
      hypertension, 21% angina pectoris, 11% had had myocardial infarction, 11% stroke,
      21% had signs of peripheral arterial disease, 2% had been amputated and 21% were
      smokers. The conclusion is that in a population of patients with diabetes with
      acceptable metabolic control, complications are still a great problem.

PMID- 9597387
TI  - A standardized protocol for the rapid preparation of bacterial DNA for pulsed
      field gel electrophoresis.
AB  - A rapid method for the preparation of bacterial DNA for pulsed-field gel
      electrophoresis was developed for Gram-positive and Gram-negative bacteria. This
      method was accomplished by reducing the time for the cell lysis reaction,
      restriction endonuclease digestion, and electrophoresis to 1, 1.5, and 18 h,
      respectively. The whole procedure from the initial bacterial culture plate to the
      final analysis of restriction fragments can be completed within 24 h. This rapid
      method was successfully achieved for Staphylococcus aureus, Enterococcus
      faecalis, Neisseria gonorrhoeae, Salmonella typhimurium, Serratia marcescens, and
      Stenotrophomonas maltophilia.

PMID- 9597388
TI  - Comparison of bedside- and laboratory-inoculated Bactec high- and low-volume
      resin bottles for the recovery of microorganisms causing peritonitis in CAPD
      patients.
AB  - There is not yet a universally accepted protocol for the recovery of
      microorganisms causing peritonitis in patients on continuous ambulatory
      peritoneal dialysis (CAPD). We prospectively analyzed 343 peritoneal effluent
      specimens by three protocols: 1) 10 ml of effluent centrifuged and the pellet
      plated onto blood, MacConkey agars, and into thioglycolate broth (routine
      method); 2) 5 ml and 10 ml inoculated at the bedside into Bactec 16A and 26A
      aerobic resin-containing blood culture bottles, respectively; and 3) 5 ml and 10
      ml inoculated in the laboratory into Bactec 16A and 26A media, respectively. One
      hundred and forty (41%) peritoneal effluent specimens had microorganisms
      recovered, and, of these, 101 were recovered by routine culture compared to 117
      (p < .021), 125 (p < .0001), 115 (p < .047), and 116 (p < .032) for bedside
      inoculated 16A and 26A and for laboratory-inoculated 16A and 26A, respectively.
      Bedside-inoculated bottles were not significantly better than laboratory
      inoculated bottles, and high-volume bottles were not significantly better than
      low-volume bottles for detection of patients positive for microorganisms;
      however, the number of total microorganisms recovered were significantly better
      from all inoculated blood culture bottles compared to routine culture. Bedside-
      and laboratory-inoculated resin-containing blood culture bottles are superior to
      the routine method for recovery of microorganisms causing peritonitis in CAPD
      patients.

PMID- 9597389
TI  - National epidemiology of mycoses survey: a multicenter study of strain variation
      and antifungal susceptibility among isolates of Candida species.
AB  - The National Epidemiology of Mycoses Survey (NEMIS) involves six academic centers
      studying fungal infections in surgical and neonatal intensive care unit (ICU)
      patients. We studied variation in species and strain distribution and anti-fungal
      susceptibility of 408 isolates of Candida spp. Candida spp. were isolated from
      blood, other normally sterile site cultures, abscesses, wounds, catheters, and
      tissue biopsies of 141 patients hospitalized in the surgical (107 patients) and
      neonatal (34 patients) ICUs of medical centers located in Oregon, Iowa,
      California, Texas, Georgia, and New York. Isolates were also obtained from
      selected colonized patients (16 patients) and the hands of health care workers
      (27 individuals). DNA typing was performed using pulsed field gel
      electrophoresis, and antifungal susceptibility to amphotericin B, 5
      fluorocytosine, fluconazole, and itraconazole was determined using National
      Committee for Clinical Laboratory Standards (NCCLS) methods. Important variation
      in susceptibility to itraconazole and fluconazole was noted: MICs of itraconazole
      ranged from 0.25 microgram/mL (MIC90) in Texas to 2.0 micrograms/mL (MIC90) in
      New York. Similarly, the MIC90 for fluconazole was higher for isolates from New
      York (64 micrograms/mL) compared to the other sites (8-16 micrograms/mL). In
      general, DNA typing revealed patient-unique strains; however, there were 13
      instances of possible cross-infection noted in 5 of the medical centers. Notably,
      9 of the 13 clusters involved species of Candida other than C. albicans.
      Potential transmission from patient-to-patient (C. albicans, C. glabrata, C.
      tropicalis, C. parapsilosis) and health care worker-to-patient (C. albicans, C.
      parapsilosis, C. krusei) was noted in both surgical ICU and neonatal ICU
      settings. These data provide further insight into the epidemiology of nosocomial
      candidiasis in the ICU setting.

PMID- 9597390
TI  - In vitro activity of voriconazole against Candida species.
AB  - The in vitro activity of voriconazole was compared with that of itraconazole and
      fluconazole against 181 isolates of Candida albicans, 124 isolates of Candida
      glabrata, and 20 isolates of Candida krusei obtained from the early 1980s through
      the mid-1990s. Voriconazole had greater intrinsic activity than fluconazole or
      itraconazole against all three Candida species. For C. glabrata, C. krusei, and
      C. albicans, the MIC50 values for voriconazole were 1 microgram/mL, 0.5
      microgram/mL, and 0.01 microgram/mL, respectively compared with fluconazole MIC50
      values of 8 micrograms/mL, 64 micrograms/mL, and 0.25 microgram/mL, respectively.
      If isolates from AIDS patients were excluded, MIC values for isolates from the
      1990s were no higher than those noted for isolates from the 1980s. Voriconazole,
      a new triazole antifungal agent, appears to have enhanced activity against these
      three species of Candida; the clinical relevance of these findings should be
      studied in treatment trials.

PMID- 9597391
TI  - Comparison of in vitro activity of trovafloxacin against gram-positive and gram
      negative organisms with quinolones and beta-lactam antimicrobial agents.
AB  - The in vitro activity of trovafloxacin against 721 Gram-negative and 498 Gram
      positive organisms was determined by the standard microdilution broth method
      using commercially prepared frozen microtiter plates. The activity of
      trovafloxacin was compared to ofloxacin, ciprofloxacin, amoxicillin/clavulanate,
      ampicillin/sulbactam (1:1), piperacillin/tazobactam, ceftriaxone, and imipenem.
      Trovafloxacin had equal or greater activity compared with the other agents tested
      against Citrobacter diversus, Enterobacter aerogenes, Enterobacter cloacae,
      Escherichia coli, Haemophilus influenzae, Stenotrophomonas maltophilia, Serratia
      marcescens, staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes,
      Streptococcus viridans, group G streptococci, Enterococcus faecalis, and E.
      faecium. The reliability of the commercially prepared plates for testing the in
      vitro activity of the quinolones was evaluated by comparing identical isolates
      also tested by broth microdilution using laboratory prepared plates. The
      commercially prepared plates generally correlated, within one- to twofold
      dilutions, with the laboratory prepared plates. There was, however, a large
      discrepancy obtained when testing Enterobacter agglomerans and E. cloacae, where
      the commercially prepared plates yielded a significantly higher MIC90 value.

PMID- 9597392
TI  - In vitro evaluation of sparfloxacin activity and spectrum against 24,940
      pathogens isolated in the United States and Canada, the final analysis.
AB  - Sparfloxacin, a recently marketed oral fluoroquinolone, was tested against 24,940
      recent clinical strains isolated from blood stream and respiratory tract cultures
      at 187 hospitals in the USA and Canada. Sparfloxacin activity was compared with 5
      to 13 antimicrobial agents using either Etest (AB BIODISK, Solna, Sweden) and a
      reference broth microdilution or a standardized disk diffusion method. When
      applying recommended MIC breakpoint criteria of sparfloxacin susceptibility (< or
      = 0.5 microgram/mL) for Streptococcus pneumoniae (4,410 strains) and other
      Streptococcus spp. (554 isolates), 93% and 88% were inhibited, respectively.
      Furthermore, at < or = 1 microgram/mL sparfloxacin susceptibility rates for
      streptococci increased to 98% overall and 99.3% for S. pneumoniae. In contrast,
      only 46% and 68% of pneumococci were susceptible to ciprofloxacin (MIC90, 3
      micrograms/mL; susceptible at < or = 1 microgram/mL) and penicillin (MIC90, 1.5
      microgram/mL; susceptible at < or = 0.06 microgram/mL), respectively. Differences
      between regions in the USA for rates of penicillin-resistant pneumococcal strains
      were observed (greatest resistances in southeast and midwest), but results
      indicate that the sparfloxacin potency was not adversely influenced (MIC90, 0.5
      microgram/mL). Also pneumococcal isolates from the lower respiratory tract were
      more resistant to penicillin and other beta-lactams. Nearly all Haemophilus
      species and Moraxella catarrhalis strains, including those harboring beta
      lactamases, were susceptible to tested fluoroquinolones (sparfloxacin,
      ciprofloxacin), amoxicillin/clavulanic acid, and newer oral cephalosporins.
      Sparfloxacin was very active against oxacillin-susceptible Staphylococcus aureus
      (MIC90, 0.12 microgram/mL; 96-97% susceptible), Klebsiella spp. (MIC90 0.12
      microgram/mL), and other tested enteric bacilli (92-95% susceptible). Comparisons
      between the broth microdilution MIC and disk diffusion interpretive results
      demonstrated excellent intermethod susceptibility category agreement (> 95%)
      using current sparfloxacin breakpoints, but some compounds (cefpodoxime disk
      diffusion tests for S. aureus) may require modifications. These results
      demonstrate that new Gram-positive focused fluoroquinolones (sparfloxacin)
      possess an excellent in vitro activity and spectrum against pathogens that cause
      respiratory tract infections. This spectrum of activity includes strains
      resistant to other antimicrobial classes, including the oral cephalosporins,
      macrolides, amoxicillin/clavulanic acid, and earlier fluoroquinolones
      (ciprofloxacin, ofloxacin). Overall, sparfloxacin inhibited 89% to nearly 100% of
      the isolates (species variable) tested against those species against which it has
      Food and Drug Administration indications for clinical use.

PMID- 9597393
TI  - National surveillance of nosocomial blood stream infection due to Candida
      albicans: frequency of occurrence and antifungal susceptibility in the SCOPE
      Program.
AB  - Surveillance of nosocomial blood stream infections (BSI) in the USA between April
      1995 and June 1996 revealed that Candida was the fourth leading cause of
      nosocomial BSI, accounting for 8% of all infections. Fifty-two percent of 379
      episodes of candidemia were due to Candida albicans. In vitro susceptibility
      studies using the 1997 National Committee for Clinical Laboratory Standards
      reference method demonstrated that 92% of C. albicans isolates were susceptible
      to 5-fluorocytosine and 90% were susceptible to fluconazole and itraconazole.
      Geographic variation in susceptibility of fluconazole and itraconazole was
      observed. Isolates from the Northwest and Southeast regions were more frequently
      resistant to fluconazole (13.3-15.5%) and to itraconazole (17.2-20.0%) than those
      from the Northeast and Southwest regions (2.9-5.5% resistant to fluconazole and
      itraconazole). Continued surveillance for infections caused by C. albicans and
      other species of Candida among hospitalized patients is recommended.

PMID- 9597394
TI  - Coronary angiography and revascularization after acute myocardial infarction:
      which rate is right?

PMID- 9597395
TI  - Should we prescribe antioxidants to patients with coronary heart disease?

PMID- 9597396
TI  - Is creatine supplementation helpful for patients with chronic heart failure?

PMID- 9597397
TI  - Ten year risk of subsequent infarction and death following admission to a
      coronary care unit.

PMID- 9597398
TI  - Does gender make a difference in patients with stable angina pectoris?

PMID- 9597399
TI  - The search for the position of the signal-averaged electrocardiogram in risk
      stratification after acute myocardial infarction.

PMID- 9597400
TI  - Diagnostic criteria in hypertrophic cardiomyopathy--another paradigm shift.

PMID- 9597401
TI  - Mechanical bridge to myocardial recovery.

PMID- 9597402
TI  - Anticoagulation for cardioversion of atrial arrhythmias.
AB  - We would advocate 3 weeks of anticoagulation prior to, and 4 weeks post
      cardioversion (either electrical or chemical) for patients in chronic atrial
      fibrillation or flutter. In selected cases it seems reasonable to use
      transoesophageal echocardiography to exclude preformed thrombus and negate the
      need for 3 weeks of prior anticoagulation. For patients presenting acutely with
      atrial fibrillation or flutter we suggest anticoagulating with heparin
      immediately on presentation and for those who do not spontaneously revert to
      sinus rhythm, using transoesophageal echocardiography to exclude atrial thrombi
      prior to cardioversion. Oral anticoagulation should be continued for 4 weeks post
      procedure. If transoesophageal echocardiography is not readily available an
      alternative strategy would be to anticoagulate the patient for 3 weeks and
      thereafter readmit them for elective cardioversion, continuing the
      anticoagulation for a further 4 weeks after the procedure.

PMID- 9597403
TI  - Cardiac and paracardiac masses. Current opinion on diagnostic evaluation by
      magnetic resonance imaging.

PMID- 9597404
TI  - 5993 survivors of suspected myocardial infarction. 10 year incidence of later
      myocardial infarction and subsequent mortality.
AB  - AIMS: To evaluate the 10-year incidence of later infarction and subsequent
      mortality, as well as predictors of later infarction, in patients with suspected
      myocardial infarction and alive on day 15 after admission. METHODS AND RESULTS:
      5993 patients admitted with suspected myocardial infarction and alive on day 15
      after admission were registered in The First Danish Verapamil Infarction Trial
      database in 1979-81. 2586 had definite infarction, 402 probable infarction and
      3005 no infarction as they fulfilled 3, 2 and 1 criteria for infarction. They
      were followed for 10 years with respect to later infarction and death, i.e.,
      including death after later infarction. The 10 year infarction rate after index
      admission was 48.8% in definite, 47.3% in probable and 24.6% in no infarction
      patients (P < 0.0001). The subsequent 10-year mortality was 82.3% in primary
      definite, 74.7% in primary probable, and 77.9% in primary no infarction patients
      (ns), Cox regression analysis with sex, age group, and definite, probable or no
      infarction as independent variables showed that females aged < 50 years without a
      primary infarction had the lowest hazard ratio (0.13 relative to males, aged 50
      65 years with definite/probable infarction at index admission) for a later
      infarction, in contrast to the highest hazard ratio (1.17) for males aged > 65
      years with definite or probable infarction. CONCLUSION: The 10-year infarction
      rate in patients with suspected myocardial infarction in whom the diagnosis is
      ruled out is lower than in those with definite or probable infarction, but the
      mortality after a later infarction is similar in all three groups.

PMID- 9597405
TI  - Increased fibrinogen levels are associated with persistent Chlamydia pneumoniae
      infection in unstable coronary artery disease.
AB  - AIM: Increased levels of acute phase proteins, e.g., fibrinogen, are related to a
      poor outcome in unstable coronary artery disease, but the cause of inflammation
      is unknown. We therefore investigated the prevalence of persistent Chlamydia
      pneumoniae infection, and its relationship to inflammation in this condition.
      METHODS AND RESULTS: In 256 patients participating in the FRISC trial, evaluating
      the effects of dalteparin (a low molecular weight heparin) in unstable angina or
      non-Q wave myocardial infarction, Chlamydia pneumoniae IgA antibody titres and
      levels of fibrinogen, C-reactive protein and troponin T were determined at
      inclusion. Increased C. pneumoniae IgA antibody titres were significantly more
      common in the patients (36%) than in a reference population of similar age (19%);
      P < 0.001. Raised titres were associated with male gender, increasing age,
      smoking, and elevated concentrations of fibrinogen, C-reactive protein and
      troponin T. The association between persistent C. pneumoniae infection and
      increased fibrinogen levels was independent of other risk factors evaluated in
      multivariate analysis (P = 0.009). CONCLUSION: Persistent C. pneumoniae infection
      is common in unstable coronary artery disease. The independent association
      between increased C. pneumoniae IgA antibody titres and fibrinogen levels
      indicates that chronic infection could be of importance for disease activity.

PMID- 9597406
TI  - Ischaemia during exercise and ambulatory monitoring in patients with stable
      angina pectoris and healthy controls. Gender differences and relationships to
      catecholamines.
AB  - AIMS: To evaluate signs of ischaemia and ventricular arrhythmias in relation to
      gender and sympathoadrenal activity in patients with stable angina pectoris and
      healthy controls. MATERIAL AND METHODS: 809 patients (248 females) with stable
      angina pectoris, and 50 matched healthy controls performed an exercise test and
      an ambulatory ECG recording. Catecholamines were measured in plasma before and
      immediately after exercise, and in urine during ambulatory ECG. RESULTS: Male and
      female patients showed similar frequencies of ST-depression, similar blood
      pressure and catecholamine responses on exercise testing. Females had higher
      heart rates and were more prone towards silent ischaemia. The healthy controls
      exercised longer and showed greater adrenaline responses. During ambulatory ECG,
      the two genders had similar duration of ST-depression, but males had more
      premature ventricular complexes. Females excreted more noradrenaline, and had
      higher minimal and maximal heart rates. Premature ventricular complexes were
      equally common among patients and controls, but controls had greater
      catecholamine excretion. Maximal ST-depression during exercise was positively
      related to the duration of ST-depression during ambulatory ECG for both genders.
      Exercise time until ST-depression was inversely related to the duration of ST
      depression during ambulatory ECG among male patients only. Catecholamine
      responses during exercise testing were more closely correlated to time until
      chest pain than to signs of ischaemia. CONCLUSION: Mechanisms behind myocardial
      ischaemia and arrhythmias may differ in male and female patients, as females seem
      to be more prone towards silent ischaemia. Ischaemia on exercise correlated to
      ambulatory ischaemia among males only.

PMID- 9597407
TI  - Long-term prognosis after acute myocardial infarction in patients with a history
      of arterial hypertension. TRACE study group.
AB  - AIMS: The objective of the study was to investigate the influence of a history of
      arterial hypertension on long-term prognosis after an acute myocardial infarction
      in a representative population, and secondly to assess the impact on prognosis of
      left ventricular systolic function in hypertensives after acute myocardial
      infarction. METHODS: A retrospective analysis of survival data on 6676 patients
      with acute myocardial infarction screened for entry into the TRAndolapril Cardiac
      Evaluation (TRACE) study. Follow-up time was 4-6 years. RESULTS: One thousand
      five hundred and seven (23%) of the patients had a history of arterial
      hypertension. During the time of observation 763 (50.6%) hypertensives and 2253
      (43.7%) normotensives died, corresponding to a risk ratio for death in
      hypertensives of 1.23 (1.13-1.33, P < 0.0001). In a multivariate analysis
      considering 12 other major risk factors after myocardial infarction, the risk
      ratio for death in hypertensives was 1.14 (1.04-1.24). There was a significant
      interaction between hypertension and age. Thus, hypertension only increased risk
      in patients aged 65 years or less (P < 0.001). No interaction with left
      ventricular systolic function was found. CONCLUSION: A history of arterial
      hypertension is a moderate risk factor for mortality after an acute myocardial
      infarction in patients aged 65 years or less. This excess risk is present at all
      levels of left ventricular systolic function.

PMID- 9597408
TI  - Early and late results and the effects on pulmonary arteries of balloon
      dilatation of the right ventricular outflow tract in tetralogy of Fallot.
AB  - BACKGROUND: Balloon dilatation of the pulmonary valve remains controversial as a
      palliative procedure in tetralogy of Fallot. AIMS: To determine the clinical
      outcome, growth of the pulmonary vascular tree and findings at surgery of balloon
      dilatation of the pulmonary valve performed as a palliation in infants with
      tetralogy of Fallot. METHODS AND RESULTS: Thirty-three severely cyanosed infants
      (mean age of 3 months for the whole population, including seven neonates)
      underwent this procedure from June 1990 to January 1997. After balloon
      dilatation, systemic oxygen saturation increased from a mean value of 76 +/- 9%
      to 88 +/- 7% (P < 0.001). The procedure was accomplished without complications.
      Four patients had recurrent hypoxic spells after dilatation leading to surgical
      repair within 30 days of dilatation (three modified Blalock-Taussig shunts and
      one complete repair). A control study was performed at a mean of 6.1 +/- 4.5
      months after dilatation in 16 patients to establish growth of the pulmonary
      vascular tree (repeat catheterization in nine patients and surgical pulmonary
      annulus calibration in seven). The pulmonary annulus increased from a mean Z
      score of -4.1 +/- 0.9 SD to -2.5 +/- 1.1 SD (P < 0.001). Z score for the right
      pulmonary artery from -3.0 +/- 0.6 SD to -1.9 +/- 1.2 SD (P = 0.007) and the Z
      score for the left pulmonary artery from -2.7 +/- 0.7 SD to -1.6 +/- 1.3 SD (P =
      0.021). At late follow-up (mean of 9 months after dilatation, range 3 to 54
      months), 28 patients underwent complete repair. Trans-annular patching was
      required in 43% of patients. Four post-operative deaths were observed, none
      dilatation related. CONCLUSION: Balloon dilatation of the pulmonary valve is an
      effective and safe palliation in tetralogy of Fallot. It promotes growth of the
      pulmonary vascular tree, reducing the need for trans-annular patching and is
      recommended in symptomatic infants of very young age, with a small pulmonary
      annulus (Z value below -4 SD) and associated cardiac anomaly.

PMID- 9597409
TI  - Increasing arterial wall injury after long-term implantation of two types of
      stent in a porcine coronary model.
AB  - AIMS: There is increased late loss in luminal diameter following long-term
      coronary stenting, compared with balloon angioplasty. We evaluated short- and
      long-term vessel wall injury after experimental implantation of two stent designs
      as well as balloon angioplasty and their relationship to neointimal hyperplasia.
      METHODS AND RESULTS: Wiktor stents and Palmaz-Schatz stents were implanted in
      normal coronary arteries of pigs (balloon/artery ratio: 0.9-1.1). In control
      coronary arteries, balloon angioplasty was performed. At 1, 4 and 12 weeks, the
      vessel injury score, neointimal thickness and inflammatory response were assessed
      by histology. The vessel injury score increased over time in both Wiktor and
      Palmaz-Schatz stents: 0.9 +/- 0.1, 1.5 +/- 0.5 and 1.7 +/- 0.6 (mean +/- SD) for
      Wiktor stents and 0.7 +/- 0.2, 1.0 +/- 0.1 and 1.2 +/- 0.3 for Palmaz-Schatz
      stents at 1, 4 and 12 weeks follow-up, respectively. No increase in injury was
      seen in balloon angioplasty controls. Inflammation was seen in both stented
      groups but was absent 12 weeks after balloon angioplasty. No strong correlation
      between injury and neointimal thickness was apparent. CONCLUSION: Stents induce
      chronic injury in contrast to balloon angioplasty. Stent design (coil vs slotted
      tube) as well as inflammation may influence vessel response.

PMID- 9597410
TI  - Simplified percutaneous mitral valvuloplasty with the Inoue balloon.
AB  - BACKGROUND: Percutaneous mitral valvuloplasty with the Inoue balloon is
      conventionally performed with double vascular access: arterial and venous.
      However, in patients with a good echogenic window it may be performed with venous
      access only and the procedure monitored by 2D-echocardiography and colour flow
      mapping. This should result in early ambulation and hospital discharge with
      reduced arterial complications. AIMS: To compare retrospectively the immediate
      results of percutaneous mitral valvuloplasty with the Inoue balloon in two groups
      of patients: Group I: venous access only (no arterial access, n = 102) and Group
      II: conventional double vascular access (arterial and venous access, n = 275).
      METHODS AND RESULTS: The baseline characteristics of the two groups were
      comparable for age, sex, clinical, echocardiographic, radiological and
      haemodynamic variables. The mitral valve area (Group I: 1.1 +/- 0.3 to 1.85 +/-
      0.5 cm2 vs Group II: 1.05 +/- 0.2 to 1.85 +/- 0.5 cm2, P = ns) and transmitral
      gradient (Group I: 11 +/- 4 to 4.7 +/- 2 mmHg vs Group II: 12 +/- 4 to 4.8 +/- 2
      mmHg, P = ns) before and after mitral valvuloplasty were not statistically
      different. A good immediate result, defined as mitral valve area > 1.5 cm2 and
      mean mitral gradient < 5 mmHg with mitral regurgitation < or = 2+ at the end of
      the procedure, was observed in 77% of the cases in the venous-only group and 79%
      in the double access group (P = ns). The incidence of severe mitral regurgitation
      (Grade III or IV) was not statistically significant. Procedural duration (71 +/-
      24 min vs 109 +/- 26 min, P < 0.01), fluoroscopic time (12.5 +/- 5.5 min vs 18.5
      +/- 6 min, P < 0.01) and hospital stay (2.8 +/- 1.5 days vs 4.8 +/- 2.6 days, P <
      0.001) were significantly shorter in the venous-only group than in the
      conventional Inoue series. CONCLUSION: Single venous access balloon mitral
      valvuloplasty is as equally safe and effective as double vascular access. The
      additional advantages of single venous access are shorter procedural duration,
      fluoroscopic time and hospital stay. We recommend that it be performed by an
      experienced operator (minimum of 100 trans-septal punctures) in patients without
      major thoracic deformity and a good echogenic window.

PMID- 9597411
TI  - The effect of dietary creatine supplementation on skeletal muscle metabolism in
      congestive heart failure.
AB  - AIMS: To assess the effects of dietary creatine supplementation on skeletal
      muscle metabolism and endurance in patients with chronic heart failure. METHODS:
      A forearm model of muscle metabolism was used, with a cannula inserted
      retrogradely into an antecubital vein of the dominant forearm. Maximum voluntary
      contraction was measured using handgrip dynanometry. Subjects performed handgrip
      exercise, 5 s contraction followed by 5 s rest for 5 min at 25%, 50%, and 75% of
      maximum voluntary contraction or until exhaustion. Blood was taken at rest and 0
      and 2 min after exercise for measurement of lactate and ammonia. After 30 min the
      procedure was repeated with fixed workloads of 7 kg, 14 kg and 21 kg. Patients
      were assigned to creatine 20 g daily or matching placebo for 5 days and returned
      after 6 days for repeat study. RESULTS: Contractions (median (25th, 75th
      interquartiles)) until exhaustion at 75% of maximum voluntary contraction
      increased after creatine treatment (8 (6, 14) vs 14 (8, 17), P = 0.025) with no
      significant placebo effect. Ammonia per contraction at 75% maximum voluntary
      contraction (11.6 mumol/l/contraction (8.3, 15.7) vs 8.9 mumol/l/contraction
      (5.9, 10.8), P = 0.037) and lactate per contraction at 75% maximum voluntary
      contraction (0.32 mmol/l/contraction (0.28, 0.61) vs 0.27 mmol/l/contraction
      (0.19, 0.49), P = 0.07) fell after creatine but not after placebo. CONCLUSIONS:
      Creatine supplementation in chronic heart failure augments skeletal muscle
      endurance and attenuates the abnormal skeletal muscle metabolic response to
      exercise.

PMID- 9597412
TI  - Sympathetic deactivation by growth hormone treatment in patients with dilated
      cardiomyopathy.
AB  - AIMS: We examined the effects of growth hormone administration on the sympathetic
      nervous system in patients with idiopathic dilated cardiomyopathy. BACKGROUND:
      Growth factor therapy is emerging as a new potential option in the treatment of
      heart failure. Although growth hormone provides functional benefit in the short
      term, it is unknown whether it affects the sympathetic nervous system, which
      plays a role in the progression of heart failure. METHODS: Seven patients with
      idiopathic cardiomyopathy received 3 months treatment with recombinant human
      growth hormone (0.15-0.20 IU.kg-1.week-1). Standard medical therapy was
      unchanged. Myocardial norepinephrine release, both at rest and during submaximal
      physical exercise, plasma aldosterone, and plasma volume were measured before and
      after growth hormone treatment. Myocardial norepinephrine release was assessed
      from arterial and coronary venous plasma concentrations of unlabelled and
      tritiated norepinephrine and coronary plasma flow (thermodilution). RESULTS:
      Growth hormone induced a significant fall in myocardial norepinephrine release in
      response to physical exercise (from 180 +/- 64 to 99 +/- 34 ng.min-1; P < 0.05).
      Basally, plasma aldosterone was 189 +/- 28 and 311 +/- 48 pg.ml-1 in the supine
      and upright position, respectively, and fell to 106 +/- 16 (P < 0.01) and 182 +/-
      29 pg.ml-1 (P < 0.05) after growth hormone therapy. Growth hormone increased
      plasma volume from 3115 +/- 493 ml to 3876 +/- 336 ml (P < 0.05), whereas serum
      sodium and potassium concentrations were unaffected. CONCLUSIONS: The data
      demonstrate that growth hormone administration to patients with idiopathic
      cardiomyopathy reduces myocardial sympathetic drive and circulating aldosterone
      levels. This neurohormonal deactivation may be relevant to the potential, long
      term use of growth hormone in the treatment of patients with heart failure.

PMID- 9597413
TI  - Comparison of the new acceleration spectrum analysis with other time- and
      frequency-domain analyses of the signal-averaged electrocardiogram.
AB  - AIM: To compare four analysis techniques of the signal-averaged
      electrocardiogram, including time-domain, spectral temporal mapping, spectral
      turbulence analysis and the new acceleration spectrum analysis. METHODS AND
      RESULTS: We studied 634 subjects (77 with bundle branch block) divided into three
      groups. Group 1 comprised 117 post-myocardial infarction patients tested for
      inducibility of sustained ventricular tachycardia, and which was induced in 54 of
      them. Group 2 comprised 407 consecutive acute myocardial infarction survivors,
      followed for 1 year; 29 of them had suffered major arrhythmic events: 15 were
      cases of sustained ventricular tachycardia, three resuscitated ventricular
      fibrillation and 11 sudden cardiac death. Group 3 comprised 110 control subjects.
      The different analysis techniques were compared by their likelihood ratio for the
      prediction of ventricular tachycardia inducibility (Group 1) or major arrhythmic
      events (Group 2). The likelihood ratios of spectral-turbulence-analysis,
      acceleration spectrum analysis, spectral temporal mapping and time-domain were
      8.0, 3.3, 1.7, 1.3 in Group 1, and 3.8, 2.1, 1.5, 2.6, in Group 2, while the
      corresponding false-positive rates in Group 3 (control) were 0.9%, 10.0%, 4.5%,
      and 3.6%, respectively. CONCLUSION: Spectral turbulence analysis was the most
      accurate technique for the prediction of either ventricular tachycardia
      inducibility or major arrhythmic events after myocardial infarction. It also
      showed the highest specificity among control subjects.

PMID- 9597414
TI  - Influence of the postoperative period and surgical procedure on ambulatory blood
      pressure-determination of hypertension load after successful surgical repair of
      coarctation of the aorta.
AB  - AIMS: This study quantified hypertension load using 24-h ambulatory blood
      pressure monitoring after successful repair of coarctation of the aorta less than
      (1) or more than 10 years previously (2) and examined the influence of the
      surgical procedure (anastomosis or subclavian flap). METHODS AND RESULTS:
      Ambulatory blood pressure recordings were obtained using an Accutracker II
      monitor every 30 min during the day and hourly, at night. Day and night systolic
      and diastolic values were higher in coarctation of the aorta than in controls:
      (day: systolic blood pressure/diastolic blood pressure: 133/71 +/- 6/4 vs 115/66
      +/- 3/2 night: systolic blood pressure/diastolic blood pressure: 117/61 +/- 4/4
      vs 107/57 +/- 3/2 mmHg, P < 0.01) and at all times, were higher in coarctation of
      the aorta (2) than in coarctation of the aorta (1). Clinical daytime systolic
      hypertension was observed in 20% of recordings from coarctation of the aorta (1)
      and 49% from coarctation of the aorta (2) while diastolic hypertension was not
      observed. However, systolic blood pressure and diastolic blood pressure responses
      to daily activities were significantly higher in coarctation of the aorta than in
      controls and this was more marked in coarctation of the aorta (2) than in
      coarctation of the aorta (1). Type of surgery did not affect either hypertension
      prevalence or blood pressure reactivity. CONCLUSIONS: These observations indicate
      exaggerated systolic blood pressure and diastolic blood pressure reactivity after
      repair of coarctation of the aorta, the prevalence of systolic hypertension
      doubling 10 years after surgery.

PMID- 9597415
TI  - Psychopathology in young adults with congenital heart disease. Follow-up results.
AB  - AIMS: The aim of the present study was to assess the occurrence of a wide range
      of behavioural and emotional problems long-term (> 9 years) after surgical
      correction for congenital heart disease in infancy and childhood. METHODS: The
      problem scores on the Young Adult Self-Report of 166 19-25-year-old adults with
      congenital heart disease were compared with those of subjects of similar age from
      the general population. RESULTS: On most Young Adult Self-Report scales no
      differences were found between the mean problem scores of the congenital heart
      disease-adults and reference peers. On only two Young Adult Self-Report scales
      (i.e. Somatic Complaints and Strange) and the total problem score were
      significant though small differences found between the mean problem scores of the
      congenital heart disease adults and reference peers. No significant relationship
      was found between cardiac diagnosis and problem behaviours in congenital heart
      disease adults. No relationship was found between IQ scores and problem
      behaviours in congenital heart disease adults. CONCLUSION: Overall, it can be
      concluded that the results of the congenital heart disease adults were not
      unfavourable, since the differences in mean (total) problem scores between the
      congenital heart disease sample and reference group were small and limited to
      only two specific problem areas.

PMID- 9597416
TI  - Comparison of the proximal flow convergence method and the jet area method for
      the assessment of the severity of tricuspid regurgitation.
AB  - AIMS: To compare the value of the proximal flow convergence method and the jet
      area method for the determination of the severity of tricuspid regurgitation.
      METHODS AND RESULTS: The proximal isovelocity surface area radius and the jet
      area/length were measured in 71 consecutive patients with angiographically graded
      (grade 0/I-III) tricuspid regurgitation. Rank correlation coefficients with the
      angiographic grade were 0.71 (P < 0.001) for the proximal isovelocity surface
      area radius (aliasing border of 28 cm.s-1), 0.66 (P < 0.001) for the jet area,
      and 0.63 (P < 0.001) for the jet length. The proximal isovelocity surface area
      radius was significantly correlated with the jet area/length (correlation
      coefficients 0.82/0.77, P < 0.001). Correct differentiation between mild to
      moderate (grade I-II) and severe (grade III) tricuspid regurgitation was achieved
      in 62 of 71 patients (87%) by means of the proximal isovelocity surface area
      radius, in 61 of 71 (86%) by the jet area, and in 62 of 71 (87%) by the jet
      length. Grade III tricuspid regurgitation was not identified in five of 21
      patients (24%) by means of the proximal isovelocity surface area radius, in six
      of 21 (29%) by the jet area, and in seven of 21 (33%) by the jet length.
      CONCLUSION: The flow convergence method and the jet area method are of similar
      value for the determination of the severity of tricuspid regurgitation. Both
      methods differentiated mild to moderate from severe tricuspid regurgitation in
      most patients. However, underestimation of severe tricuspid regurgitation in 20
      30% of the cases represents a serious limitation of both methods.

PMID- 9597417
TI  - Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary
      blood flow and myocardial substrate utilization early after coronary artery
      bypass grafting.
AB  - AIMS: The aim of the study was to evaluate the effects on systemic and coronary
      haemodynamics and myocardial substrate utilization of a new calcium sensitizer,
      levosimendan, after coronary artery bypass grafting. METHODS AND RESULTS: Twenty
      three low-risk patients were included in this randomized and double-blind study.
      They received placebo (n = 8), 8 (n = 8) or 24 (n = 7) micrograms.kg-1 of
      levosimendan after coronary artery bypass operation. Systemic and coronary sinus
      haemodynamics with thermodilution and myocardial substrate utilization were
      measured. The heart rate increased 11 beats.min-1 after the higher dose (P <
      0.05). Cardiac output increased by 0.7 and 1.61.min-1 (P < 0.05 for both) after 8
      and 24 micrograms.kg-1 of levosimendan, respectively. Systemic and pulmonary
      vascular resistance decreased significantly after both doses. Coronary sinus
      blood flow increased by 28 and 42 ml/(P = 0.054 for the combined effect) after
      the lower and higher dose, respectively. Myocardial oxygen consumption or
      substrate extractions did not change statistically significantly. CONCLUSION:
      Despite improved cardiac performance, levosimendan did not increase myocardial
      oxygen consumption or change myocardial substrate utilization. Thus levosimendan
      has the potential to treat low cardiac output states after cardiopulmonary bypass
      surgery.

PMID- 9597418
TI  - Prevalence and relevance of a septal diastolic notch during dobutamine stress
      echocardiography.
AB  - BACKGROUND: Dobutamine stress echocardiography has become an accepted simple and
      inexpensive method of detecting coronary artery disease. In this pharmacological
      stress test, particular attention has been paid to transient systolic wall motion
      abnormalities. Our group has noted an abnormal diastolic ventricular septal
      motion, a 'diastolic notch', during dobutamine stress echocardiography that has
      not been previously described. METHODS AND RESULTS: To find out whether this
      anomalous septal motion is related to coronary artery disease we have analysed
      the stress studies of 125 patients (69 men, age 61 +/- 9 years) with chest pain,
      no previous myocardial infarction and no left bundle branch block, who underwent
      a dobutamine stress test. Dobutamine was infused up to 40 mu.kg.l-1 min-1 in 3
      min stages. A positive stress test was defined as the appearance of transient
      asynergy. Dobutamine time was the time from the infusion of dobutamine to the
      appearance of transient asynergy. The diastolic notch time was the time at which
      diastolic notch was first detected. Diastolic notch was detected in 21 patients
      with single coronary artery disease, 19 of whom had a severe left anterior
      descending artery stenosis. Diastolic notch was present in 19 out of 27 patients
      (70%) with single left anterior descending stenosis. Twenty-six out of 44
      patients with multivessel coronary artery disease had evidence of a diastolic
      notch and 20 of these 26 had severe stenosis of the left anterior descending
      artery. Finally, all three patients with left main coronary artery disease had a
      diastolic notch while no patient with angiographically normal coronary arteries
      had this sign. In patients with a diastolic notch and a positive dobutamine
      stress test, diastolic notch time was shorter than dobutamine time (9 +/- 4 min
      vs 11 +/- 3 min, P < 0.05). CONCLUSIONS: In patients without previous myocardial
      infarction and without left bundle branch block (1) the appearance of a septal
      diastolic notch during dobutamine stress echocardiography is very specific for
      the presence of coronary artery disease; (2) the detection of diastolic notch is
      mostly related to the existence of severe left anterior descending artery
      stenosis; (3) diastolic notch precedes the development of ventricular asynergy.

PMID- 9597419
TI  - History and importance of preventive medicine.

PMID- 9597420
TI  - Lipoproteins and cardiovascular risk--from genetics to CHD prevention.
AB  - Increased levels of low density lipoprotein (LDL) cholesterol and triglyceride,
      and low levels of high density lipoprotein (HDL) cholesterol, are associated with
      increased risk of coronary heart disease (CHD). Only a minor part of the
      variation in lipids can be explained by defects in single genes of large effect;
      the bulk of variation in most cases is due to the interaction of polygenes and
      environment. This paper describes a strategy for unravelling such complex genetic
      effects in the population at large. A person's risk of developing CHD is,
      however, not determined by levels of circulating lipids alone, but by a number of
      factors which contribute to his or her global risk. Based on the data of the
      Munster Heart Study (PROCAM), a multiple logistic function using nine independent
      variables for the prediction of risk has been developed. This function allows an
      almost 40-fold degree discrimination in risk between persons in the lowest and
      highest quintiles of the algorithm. Data from the Munster Heart Study and other
      prospective studies indicates a log-linear relationship between LDL cholesterol
      and CHD risk. The results of recent large scale intervention trials indicate that
      this relationship also holds true for LDL levels which are achieved by treatment.
      This indicates that the benefit achieved by cholesterol lowering is greatest at
      high baseline LDL cholesterol levels, and that at least for LDL cholesterol
      levels of > or = 80 mg. dl-1, there is no theoretical threshold below which
      lowering of LDL cholesterol cannot be expected to reduce CHD risk. However, at
      low LDL cholesterol levels the benefits of treatment may be outweighed by side
      effects and by practical cost-benefit considerations. These issues are also
      discussed in detail in the present report.

PMID- 9597421
TI  - Circadian variation and triggers of acute coronary syndromes.
AB  - Myocardial infarction and sudden cardiac death demonstrate a marked circadian
      variation with an increased risk during the morning after awakening and arising.
      The recognition of the morning increase of acute coronary heart disease has
      convinced many that morning activities can 'trigger' its onset. It is of note,
      however, that coronary events may occur throughout the day--even if at lower
      frequency compared with the morning. There is a strong association between
      external triggers and onset of myocardial infarction and sudden cardiac death
      beyond that expected by chance alone. The magnitude of this association (relative
      risk two- to threefold) is comparable to that of other known long term risk
      factors of cardiac disease. Trigger factors occur relatively frequently and may
      play a causative role in up to 20% of cases of acute coronary syndromes. Physical
      exertion, burst of anger and sexual activity have been proven to have triggering
      potential. Other possible triggers include external and environmental events such
      as earthquakes, war threat and climatic factors. The pathophysiological links
      between external triggers and onset of coronary syndromes are important in
      addressing the question of a causal relationship between triggers and disease
      onset and, perhaps, in improving preventive strategies.

PMID- 9597422
TI  - Coronary atherosclerosis: determinants of plaque rupture.
AB  - The most important mechanism responsible for the sudden and unpredictable onset
      of acute coronary syndromes is coronary plaque rupture with thrombosis and
      vasospasm superimposed. The risk of plaque rupture depends on plaque type
      (composition) rather than plaque size (volume); most ruptures occur in plaques
      containing a soft, lipid-rich core that is covered by a thin and inflamed cap of
      fibrous tissue. Compared with intact caps, the ruptured ones usually are thinner
      and contain less collagen (responsible for tensile strength), fewer smooth muscle
      cells (smc; collagen synthesizing cells), and many more macrophages (collagen
      degrading cells). Therefore, major determinants of plaque vulnerability and
      rupture are progressive lipid accumulation (core formation) and cap weakening due
      to ongoing inflammation with collagen degradation (macrophage-related) and
      impaired healing and repair (smc-related). These intrinsic plaque changes
      predispose plaques to rupture whereas extrinsic forces imposed on plaques, such
      as biomechanical and haemodynamic stresses, may determine the actual time of
      rupture by precipitating or 'triggering' it. Luckily, recent research in patients
      with coronary artery disease indicates that both plaque vulnerability and rupture
      triggers may be modified beneficially by treatment.

PMID- 9597423
TI  - The endothelium in acute coronary syndromes.
AB  - The coronary circulation is controlled by the central nervous system, circulating
      hormones and local vascular mechanisms. The importance of local regulatory
      mechanisms has only recently been recognized. The endothelium is in a strategical
      anatomical position within the blood vessel wall located between the circulating
      blood and vascular smooth muscle cells. It can respond to mechanical and hormonal
      signals from the blood; of particular importance is the fact that it is a source
      of mediators which can modulate the contractile state and proliferative responses
      of vascular smooth muscle cells, platelet function and coagulation as well as
      monocyte adhesion. Important relaxing factors are nitric oxide and prostacyclin
      and a putative hyperpolarizing factor. Nitric oxide also inhibits smooth muscle
      proliferation and, together with prostacyclin, platelet adhesion and aggregation.
      Bradykinin-induced nitric oxide production is regulated by angiotensin converting
      enzyme located on the endothelial cell membrane; indeed, the enzyme not only
      activates angiotensin I into angiotensin II, but also inactivates bradykinin.
      Endothelin-1 and thromboxane A2 and prostaglandin H2 are contracting factors
      produced by the endothelium. In contrast to thromboxane A2 and prostaglandin H2
      which activate platelets, endothelin has no direct effects on these cells, but
      has proliferative properties in vascular smooth muscle. Under physiological
      conditions, the endothelium plays a protective role as it prevents adhesion of
      circulating blood cells, keeps the vasculature in a vasodilated state and
      inhibits vascular smooth muscle proliferation. In disease states, however,
      endothelial dysfunction contributes to enhanced vasoconstrictor responses,
      adhesion of platelets and monocytes and proliferation of vascular smooth muscle
      cells, events all known to occur in coronary artery disease. Nitrates substitute
      in part for deficient endogenous nitric oxide, while angiotensin converting
      enzyme inhibitors increase the bradykinin induced nitric oxide and prostacyclin
      production. The newly developed endothelin antagonists allow specific blocking of
      the effects of endothelin. Pharmacological correction of endothelial dysfunction
      may be important to treat coronary artery disease and its complications.

PMID- 9597424
TI  - Haemostatic risk factors for cardiovascular diseases.
AB  - Strong evidence from large observational epidemiological studies links
      haemostatic variables to the future risk of myocardial infarction and stroke.
      Recent data provide further evidence for an early involvement of haemostatic
      parameters in atherosclerosis. So far, a variety of markers of a procoagulatory
      tendency e.g. elevated fibrinogen, coagulation factor VII, factor VIII and von
      Willebrand factor, platelet hyperaggregation, increased plasma levels of D-dimer,
      and decreased fibrinolytic capacity, e.g. characterized by increased levels of
      PAI-1 activity and decreased t-PA concentrations have been identified
      prospectively. Thus, a complex disturbed haemostatic system plays an important
      role in the development of atherothrombotic events in several vascular beds. This
      review discusses the epidemiologic evidence of the association between the
      haemostatic system and cardiovascular disease.

PMID- 9597425
TI  - Invasive strategies to discriminate stable and unstable coronary plaques.
AB  - Unstable coronary plaques with surface erosion and plaque rupture lead to acute
      coronary thrombosis, unstable angina pectoris and myocardial infarction. The in
      vivo detection of plaque instability by angiography, intravascular ultrasound or
      angioscopy or by newly developed techniques, such as optical coherence tomography
      or by the observation of local temperature increases, offers the opportunity for
      deeper understanding of the mechanisms underlying plaque rupture and erosion.
      Pharmacological and transcatheter therapy might be directed more exclusively to
      unstable plaques, once more detailed knowledge about pathophysiological
      mechanisms as well as direct information about the individual plaque being
      treated is available.

PMID- 9597426
TI  - Chronopharmacological aspects for the prevention of acute coronary syndromes.
AB  - This review discusses the circadian phase dependency in the anti-anginal effects
      and in the pharmacokinetics of drugs used in the treatment of coronary heart
      diseased patients. beta-receptor blocking agents seem mainly to reduce ischaemic
      events during daytime hours and are of therapeutic value in the morning hours
      which are the hours of high cardiovascular risk. Calcium channel blockers seem to
      be less effective in reducing ischaemic event during the night and early morning.
      However, the galenic formulation and the type of calcium channel blocker may play
      an important role. Whereas the effects of the anti-ischaemic properties of oral
      nitrates are well established, their influence of the circadian organization of
      cardiovascular events needs to be clarified. Only limited data are available
      concerning the circadian phase dependency in the dose-response relationship of
      anti-anginal drugs. Such data would be valuable for a better understanding of the
      need of a time-specified drug treatment which is based on the circadian phase
      dependency of cardiovascular events such as coronary infarction and angina
      pectoris attacks.

PMID- 9597427
TI  - Cost-effectiveness of primary and secondary prevention in cardiovascular
      diseases.
AB  - INTRODUCTION, AIMS, AND METHODS: Industrial countries' societies are challenged
      to counter the increasing costs of health care. The preponderance of
      cardiovascular diseases in middle-aged people demands new strategies to reduce
      the extremely high rates of early deaths and increased morbidity and thus to
      avert considerable costs. Prevention programmes are appropriate means to combine
      therapeutic needs with health economic goals. A review of techniques of economic
      evaluation is given, from which a critical appraisal of cost-effectiveness
      analyses in primary and secondary prevention with HMG-CoA reductase inhibitors in
      coronary heart disease follows. Our own analysis of cost-effectiveness of primary
      prevention based on the clinical results of the WOSCOP study is also presented.
      RESULTS AND CONCLUSIONS: Long-term treatment with HMG-CoA reductase inhibitors is
      effective (30% mortality reduction), safe and tolerable. With a cost
      effectiveness ratio of DM15,000-25,000/life-year saved ($9000-15,000) it can be
      recommended for secondary prevention. The application of statins in primary
      prevention has also proved to be clinically effective. But with a cost
      effectiveness ratio of DM330,000/life-year saved ($195,000) they cannot be
      generally advocated in patients with hypercholesterolaemia. However, the
      treatment has to be considered for high risk patients. Aspirin prevention seems
      to be an alternative in patients without additional risk factors.

PMID- 9597428
TI  - [Clinical effects of long-term administration of macrolide antibiotics to
      patients with chronic paranasal sinusitis: results of past reports].

PMID- 9597429
TI  - [Status of long-term administration of macrolide antibiotics in small dosages: a
      survey based on questionnaires].

PMID- 9597430
TI  - [Efficacy of macrolide antibiotics in chronic paranasal sinusitis].

PMID- 9597431
TI  - [Efficacy of clarithromycin on chronic paranasal sinusitis--a comparison between
      children and adult].

PMID- 9597432
TI  - [Expression of MHC-II in the paranasal sinus mucosa of patients treated with
      macrolide antibiotics].

PMID- 9597433
TI  - [Structures and actions of macrolide antibiotics].

PMID- 9597434
TI  - [Evaluation of antineoplastic effect of CAM (clarithromycin) in a mouse model
      inoculated with lung cancer cells].

PMID- 9597435
TI  - [Effects of macrolide antibiotics to inhibit infiltration and proliferation of
      malignant tumor cells--in vitro evaluation].

PMID- 9597436
TI  - [Effects of clarithromycin on experimental pulmonary metastasis].

PMID- 9597437
TI  - [Efficacy of clarithromycin on cancer cachexia in patients with primary non-small
      cell lung cancer].

PMID- 9597438
TI  - [Fluctuation in the cytokine m-RNA content in primary non-small cell lung cancer
      caused by clarithromycin (CAM) administration].

PMID- 9597439
TI  - [Effect of clarithromycin on prolonging the life expectancy of patients with
      primary lung cancer].

PMID- 9597440
TI  - [Effect of clarithromycin in extending the life expectancy of patients with non
      small-cell lung cancer].

PMID- 9597441
TI  - [Effects of erythromycin and roxithromycin on airway goblet cell secretion].

PMID- 9597442
TI  - [Il-8 secretion by cultured epithelial cells of human nasal mucosa and its
      suppression by macrolide antibiotics].

PMID- 9597443
TI  - [Neutrophilic migration caused by nasal secretion collected from patients with
      chronic paranasal sinusitis].

PMID- 9597444
TI  - [Study of peripheral neutrophil functions of macrolide-resistant patients with
      DPB (diffuse panbronchitis) by using flow cytometry].

PMID- 9597446
TI  - [Effects of a steroid and macrolide antibiotic on IL-8 production by
      neutrophils].

PMID- 9597447
TI  - [Effect of macrolide antibiotics on actin polymerization reactions of
      neutrophils].

PMID- 9597448
TI  - [Macrolide antibiotic actions on bacteria and cultured airway cells].

PMID- 9597449
TI  - [Effect of roxithromycin on neutrophil functions: study of short-term
      administration].

PMID- 9597453
TI  - [Pyocyanine synthesis by Pseudomonas aeruginosa in chronic airway infection and
      the effect of erythromycin on its biological activity].

PMID- 9597454
TI  - [Effects of pretreatment by erythromycin or rokitamycin on aminoglycoside
      inactivating enzyme of Pseudomonas aeruginosa].

PMID- 9597455
TI  - [Actions of macrolide antibiotics on alginate production by Pseudomonas
      aeruginosa].

PMID- 9597456
TI  - [Quantitative evaluation of the inhibitory action of macrolide antibiotics on
      biofilm formation by Pseudomonas aeruginosa].

PMID- 9597457
TI  - [Preliminary survey on DPB (diffuse panbronchitis) in Japan and a survey on the
      status of DPB in China].

PMID- 9597458
TI  - [Effects and actions of EM (erythromycin), CAM (clarithromycin), and JM
      (josamycin) on IL-4 and IL-5 production by monocytes].

PMID- 9597459
TI  - [Effect of roxithromycin on cytokine production by peripheral monocytes derived
      from patients with bronchial asthma].

PMID- 9597460
TI  - [Lymphocyte subsets and beta-family chemokines in the BALF of patients with
      diffuse panbronchitis before and after treatment with macrolide antibiotics].

PMID- 9597461
TI  - [Effect of long-term administration of a small dosage of roxithromycin on mice
      monocytes--in vivo experimental study].

PMID- 9597462
TI  - [Vitamin D3 induction of differentiation of HL-60 cells to monocyte- like cells
      and their aggregation--a dynamic culture method and clarithromycin].

PMID- 9597463
TI  - [Analysis of chronic respiratory tract infection by using an intubation model-
      evaluation based on fluctuations in cytokine content].

PMID- 9597464
TI  - [C kinase activation and induction of HL 60 promyelocytic leukemia cell
      differentiation caused by roxithromycin].

PMID- 9597465
TI  - [Study of specific mRNA expression by peripheral monocytes of patients with
      diffuse panbronchitis using cDNA representational difference analysis (RDA)].

PMID- 9597466
TI  - [Study of therapeutic effects of macrolide antibiotics on patients with anti-HTLV
      1 antibody positive DPB (diffuse panbronchitis)].

PMID- 9597467
TI  - [Log-term administration of clarithromycin as a possible adjuvant therapy of HIV
      infections].

PMID- 9597468
TI  - [Effects of roxithromycin (RXM) on viruses and cultured cells].

PMID- 9597469
TI  - [Effects of erythromycin on a mouse hypersensitivity pneumonia model].

PMID- 9597470
TI  - [Effects of macrolide antibiotics on fibroblasts].

PMID- 9597471
TI  - [Effects of macrolide drugs on endogenous glucocorticoids].

PMID- 9597472
TI  - [Effect of roxithromycin on neutrophil chemotaxis and phagocytosis].

PMID- 9597473
TI  - [Study of suppression of neutrophil functions and prevention of vascular
      endothelial injury by macrolide antibiotics].

PMID- 9597474
TI  - [Effects of macrolide antibiotics on iNOS gene expression and NO production by
      alveolar macrophages].

PMID- 9597475
TI  - [Bone absorption suppression by broad spectrum antibiotics].

PMID- 9597476
TI  - [Effect of roxithromycin treatment on the IL-4, IL-5, and IFN-gamma production
      system induced by mite antigen].

PMID- 9597477
TI  - [Immunohistochemical study of the paranasal sinus mucosa of patients being
      treated with macrolide antibiotics--effects of antigen-presenting cells on the
      expression of a costimulator].

PMID- 9597478
TI  - [Study on the effects of macrolide antibiotics on the expression of B7-1, B7-2,
      and CD40 on epidermal Langerhans cells].

PMID- 9597479
TI  - [Macrolide metabolism by cytochrome P450: a difference between 14-member and 16
      member rings].

PMID- 9597480
TI  - [Effects of macrolide antibiotics on neutrophil infiltration into the airway
      mucosa and ICAM-1 expression].

PMID- 9597481
TI  - [Evaluation of soluble CD44 in the BALF before and after treatment of DPB
      (diffuse panbronchitis) with macrolide antibiotics].

PMID- 9597482
TI  - [Changes in adhesion molecule expressions in neutrophils caused by new macrolide
      administration].

PMID- 9597483
TI  - [Effects of a steroid and macrolide antibiotic on adhesion of neutrophils to the
      airway epithelial cells].

PMID- 9597484
TI  - [Effect of clarithromycin in extending the life expectancy of patients with non
      small-cell lung cancer--the second report].

PMID- 9597485
TI  - [Efficacy of clarithromycin (CAM) in patients with inoperable non-small-cell lung
      cancer].

PMID- 9597486
TI  - [Effect of clarithromycin administration on interferon-gamma and interleukin 12
      mRNA expression in the tumor tissue of non-small-cell lung cancer].

PMID- 9597487
TI  - [Evaluation of BRM (biological response modifier) action of clarithromycin (CAM)-
      effect on cytokine expression in a mouse lung cancer model].

PMID- 9597488
TI  - [Effect of clarithromycin on experimental pulmonary metastasis].

PMID- 9597489
TI  - [Tumor neovascularization inhibiting and tumor proliferation and metastasis
      suppressing actions of 14-, 15-, and 16-member ring macrolides].

PMID- 9597490
TI  - [Actions of macrosphelide, a cell adhesion inhibitor].

PMID- 9597491
TI  - [Significance of therapeutic efficacy of clarithromycin in a model for human lung
      cancer metastasis and a mouse tumor system].

PMID- 9597492
TI  - [Antineoplastic therapeutic effect of clarithromycin in rats].

PMID- 9597493
TI  - [Inhibitory effects of macrolide antibiotics on infiltration and proliferation of
      lung cancer cell lines, A-549 and SBC-3].

PMID- 9597494
TI  - [Therapeutic guideline for diffuse panbronchitis (draft). Subcommittee on Diffuse
      Lung Diseases, Research Committee on Respiratory Diseases Organized by the
      Ministry of Health and Welfare].

PMID- 9597495
TI  - [Guideline for macrolide treatment of chronic paranasal sinusitis (draft)].

PMID- 9597496
TI  - [Evaluation of the duration of medication with erythromycin for treatment of
      diffuse panbronchitis--a comparison between interruption of medication and
      continued administration].

PMID- 9597497
TI  - [Study of efficacy of macrolide therapy applied to Kartagener's syndrome].

PMID- 9597498
TI  - [Test to set dosages for long-term administration of clarithromycin to treat
      chronic paranasal sinusitis].

PMID- 9597499
TI  - [Mucous pathology and macrolide treatment of paranasal sinusitis in children].

PMID- 9597500
TI  - [Multicenter study on clinical effects of a small dose of erythromycin on chronic
      lung disorders of premature infants--single blind comparison of treated and
      untreated groups. A committee for the Study of EM Therapy for Chronic Lung
      Diseases of Premature Infants].

PMID- 9597501
TI  - [Treatment of acne by using roxithromycin and a study of the mechanism of the
      drug action].

PMID- 9597502
TI  - [Effects of macrolide antibiotics on fibroblasts (report 2)].

PMID- 9597503
TI  - [Effects of erythromycin on Pseudomonas aeruginosa pyocyanine-induced IL-8
      production and its biological activity (the 2nd report)].

PMID- 9597504
TI  - [Effect of macrolides on IL-8 gene expression by cultured airway epithelial
      cells].

PMID- 9597505
TI  - [Neutrophil count and IL-8 level of nasal secretion of patients with chronic
      paranasal sinusitis and the effects of macrolide antibiotics].

PMID- 9597506
TI  - [Changes in cytokine production by pulmonary alveolar macrophages collected from
      rats that have been treated with erythromycin for an extended period].

PMID- 9597507
TI  - [Effects of various drugs on IL-8 production by eosinophils collected from
      patients with allergic inflammation].

PMID- 9597508
TI  - [Inhibition of neutrophil-derived IL-8 production caused by EM (erythromycin) 201
      derivative: modification of the activities by the 5-position desosamine side
      chain].

PMID- 9597509
TI  - [Transport of azithromycin into infected tissue observed by macro- and
      microautoradiography].

PMID- 9597510
TI  - [Study on bacterial biofilm destruction by various antibacterial agents].

PMID- 9597511
TI  - [Inhibitory effects of macrolide antibiotics at low concentrations on vero toxin
      production by pathogenic E. coli O157].

PMID- 9597512
TI  - [Effects of macrolides on electrolyte secretion by airway ciliary epithelial
      cells].

PMID- 9597513
TI  - [Effects of macrolides on intracellular Ca2+ response by airway epithelium].

PMID- 9597514
TI  - [Mechanism of erythromycin action on gene expression of airway epithelial cells].

PMID- 9597515
TI  - [Effects of macrolide preparations on endogenous glucocorticoids-- structure
      activity relationship and a comparison with other drugs].

PMID- 9597516
TI  - [Superoxide radical scavenging activity of an erythromycin-iron complex (the
      second report)].

PMID- 9597517
TI  - Fundamentals of coagulation and glycoprotein IIb/IIIa receptor inhibition.
AB  - An understanding of the coagulation process and the role of platelets is
      essential to recognizing the shortcomings of older anticoagulant therapies and
      appreciating the clinical potential of newer forms of antiplatelet and
      anticoagulant therapy for acute coronary syndromes. The anticoagulant actions of
      heparin are severely limited by dependence on antithrombin III, neutralization by
      platelet factor 4, and the resistance of clot-bound thrombin and platelet
      membrane-bound factor Xa to the heparin-antithrombin III complex. Unlike heparin,
      the direct thrombin inhibitors (such as hirudin) are active against both
      circulating and clot-bound thrombin. However, in recent clinical trials they have
      not resulted in major improvements in patient outcome. Another new class of
      drugs, the glycoprotein IIb/IIIa receptor antagonists, blocks the final common
      pathway of platelet aggregation and is capable of preventing platelet
      accumulation at sites of injury. The net effect is a dramatic reduction in the
      amount of platelet membrane available to support the process of coagulation.
      Clinical trials with the glycoprotein IIb/IIIa inhibitors have suggested that
      this class of agents may be particularly effective in reducing the thrombotic
      complications associated with coronary interventional procedures and may be
      useful in the treatment of acute coronary syndromes.

PMID- 9597518
TI  - An overview of the results of clinical trials with glycoprotein IIb/IIIa
      inhibitors.
AB  - The era of platelet glycoprotein (GP) IIb/IIIa receptor inhibition in cardiology
      was inaugurated in 1994 with the publication of the Evaluation of 7E3 for the
      Prevention of Ischemic Complications (EPIC) trial results. EPIC demonstrated that
      the GP IIb/IIIa blocker abciximab, administered as a bolus and 12-hour infusion,
      afforded protection against ischemic complications in high-risk patients
      undergoing angioplasty and atherectomy, including those with unstable angina or
      evolving myocardial infarction (MI). A significant reduction in the incidence of
      death, acute MI, or revascularization was apparent at 30 days and also sustained
      at 6-month and 3-year follow-up. The subsequent Evaluation in PTCA to Improve
      Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG) study extended
      these findings to the full spectrum of coronary intervention patients, confirming
      that abciximab provided similar benefits in low-risk patients as well. The EPILOG
      trial also proved that any excess bleeding risk associated with potent
      antiplatelet therapy could be brought down to placebo levels through the use of a
      low-dose, weight-adjusted heparin regimen, early vascular sheath removal, and
      elimination of routine postprocedural heparinization. The potential for an
      advantage of GP IIb/IIIa blockade in patients with refractory unstable angina/non
      Q-wave MI was demonstrated in the c7E3 Fab Antiplatelet Therapy in Unstable
      Refractory Angina (CAPTURE) trial, which showed that a 24-hour preprocedural
      abciximab infusion effectively stabilized these patients, thereby enhancing the
      safety of intervention and reducing the 30-day incidence of ischemic events. A
      similar pattern of benefit has emerged from clinical trials of such other GP
      IIb/IIIa inhibitors as eptifibatide, lamifiban, and tirofiban. Trials are
      currently underway to clarify the benefits of GP IIb/IIIa blockers in patients
      undergoing stenting and as an adjunct to thrombolytic therapy or primary
      angioplasty in patients with acute MI (ST-segment elevation).

PMID- 9597519
TI  - Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute
      coronary syndromes.
AB  - Platelet glycoprotein (GP) IIb/IIIa blockade has the potential to advance
      treatment of acute coronary syndromes, both as a primary pharmacologic approach
      and an adjunct to interventional treatment strategies. The benefits of GP
      IIb/IIIa inhibition with the chimeric monoclonal antibody abciximab in preventing
      ischemic complications of interventional treatment have been well defined in
      patients with unstable angina. In the future, major therapeutic applications for
      this class of agents may include the stabilization of patients with unstable
      angina and potentially as single medical therapy, as several recently completed
      trials have suggested. Evidence also is accumulating on the use of GP IIb/IIIa
      blockade as adjunctive therapy in fibrinolytic approaches to treatment of acute
      myocardial infarction. Several ongoing trials are evaluating the safety and
      efficacy of this novel strategy. This article reflects a distillation of the
      views and consensus regarding the prospective use of GP IIb/IIIa inhibitors in
      patients with acute coronary syndromes expressed by a group of international
      experts convened in Davos, Switzerland, February 16, 1997. This report attempts
      to review clinical progress to date, formulate recommendations, and map out
      potentially fruitful lines of inquiry for future investigation.

PMID- 9597520
TI  - Use of abciximab in interventional cardiology.
AB  - The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed
      the landscape of interventional cardiology. Given the commercial availability of
      abciximab and expected regulatory approvals for other receptor blockers, defining
      appropriate use of these agents in the interventional setting is mandated. One
      key issue is selection of patients who may benefit from GP IIb/IIIa receptor
      blockade. Focusing specifically on abciximab, data from three large-scale,
      randomized trials demonstrate that abciximab is appropriate for all patients
      undergoing percutaneous transluminal coronary angioplasty, regardless of risk
      stratum. Other important issues to consider when prescribing this therapy include
      benefits in conjunction with stents and new devices, dosing and timing of
      administration, and the role of prophylactic versus "bailout" administration.
      This article reflects a distillation of the views and consensus regarding the use
      of GP IIb/IIIa inhibitors in patients undergoing coronary intervention expressed
      by a group of international experts convened in Davos, Switzerland, February 16,
      1997. This report attempts to review clinical progress to date, formulate
      recommendations, and map out potentially fruitful lines of inquiry for future
      investigation.

PMID- 9597521
TI  - Safe use of platelet GP IIb/IIIa inhibitors.
AB  - The platelet membrane glycoprotein IIb/IIIa receptor inhibitor abciximab is used
      for the treatment of patients undergoing high-risk percutaneous coronary
      interventions and is used in approximately one third of coronary interventions in
      the United States and a growing number of procedures in Europe. Recent clinical
      trials have shown that this potent antiplatelet agent significantly reduces the
      incidence of death and nonfatal myocardial infarction and the need for
      revascularization. With expanding experience since the commercial release of
      abciximab in February 1995, several strategies to enhance the safety of abciximab
      have emerged. In particular, new data confirm that the risk of bleeding-
      identified as a concern in the original EPIC trial--can be substantially reduced
      through the use of low-dose adjunctive heparin, early sheath removal, and
      fastidious postprocedure vascular access site care. Other recommendations for
      enhancing the safety of potent antiplatelet agents in a variety of clinical
      situations are provided. The following article reflects insights regarding the
      safety of glycoprotein IIb/IIIa inhibitors expressed by a group of international
      experts convened in Davos, Switzerland, February 16, 1997. This report attempts
      to review clinical progress to date, formulate recommendations, and map out
      potentially fruitful lines of inquiry for future investigation.

PMID- 9597522
TI  - Abciximab therapy in percutaneous intervention: economic issues in the United
      States.
AB  - Whether abciximab therapy should be the standard of care during percutaneous
      intervention in the United States depends on its efficacy, safety, and economics.
      In view of the EPIC, CAPTURE, and EPILOG data, few question the superior efficacy
      and relative safety of abciximab compared with conventional high-dose heparin
      therapy during percutaneous intervention. Economic considerations have been the
      major issue limiting its use. Review of the economic data demonstrates that the
      incremental direct medical care cost of abciximab therapy is $290 to $600 per
      patient treated in the EPIC and EPILOG populations. In the patients with acute
      myocardial infarction and unstable angina, abciximab appears to reduce direct
      medical costs (produce cost savings) at 6 months. Given abciximab's significant
      incremental effectiveness, its relatively small incremental cost yielded a highly
      cost-effective therapy in the EPIC and EPILOG patient populations. Additional
      economic issues relate to minimizing bleeding complications, indirect costs,
      reduced frequency of emergency procedures, and rationalizing provider/payor
      policies and incentives to produce the optimal individual patient and societal
      outcomes. The currently available data concerning the efficacy, safety, and cost
      provide a compelling argument for embracing abciximab therapy in the treatment of
      patient subsets where it will be a cost-saving or cost-neutral adjunct to
      percutaneous coronary intervention. In other subsets, the direct medical cost
      will likely not be fully recouped, but the incremental cost-effectiveness will
      compare favorably to other widely accepted therapies.

PMID- 9597524
TI  - Tracking resident procedures needs accountability.

PMID- 9597525
TI  - Can palmtop computers improve the feasibility of research projects for FM
      faculty?

PMID- 9597523
TI  - Costs and effects in therapy for acute coronary syndromes: the case of abciximab
      in high-risk patients undergoing percutaneous transluminal coronary angioplasty
      in the EPIC study. Evaluation of 7E3 for the Prevention of Ischemic
      Complications.
AB  - Cost-effectiveness analyses are routinely performed to determine whether the
      additional cost of a novel therapy is balanced by additional effectiveness. The
      definitions of costs and effects involve a variety of assumptions, both in
      general economic terms and with regard to the specific medical setting under
      consideration. Similarly, differing criteria for acceptability of cost
      effectiveness estimates can be used to generate different conclusions regarding
      cost-effectiveness. The issues and problems inherent in economic evaluation are
      discussed by an analysis of findings with the platelet glycoprotein IIb/IIIa
      inhibitor abciximab in the EPIC (Evaluation of 7E3 for the Prevention of Ischemic
      Complications) study in high-risk patients undergoing percutaneous transluminal
      coronary angioplasty.

PMID- 9597526
TI  - From managed care to managed education: how should we seize the day?

PMID- 9597528
TI  - Defining preceptor, mentor, and role model.

PMID- 9597527
TI  - Ten tips for effective teaching.

PMID- 9597529
TI  - Lions and tigers and bears, oh my!

PMID- 9597530
TI  - Tracking the contribution of a family medicine clerkship to the clinical
      curriculum.
AB  - BACKGROUND AND OBJECTIVES: Medical educators are working to articulate the
      objectives and measure the outcomes of medical education. In clinical training,
      faculty need methods to identify both the principal educational contributions of
      individual clerkships and how prior experiences influence student learning.
      METHODS: We analyzed students' perceived acquisition of clinical knowledge and
      skills on a 4-week, community-based family medicine clerkship. The data represent
      349 third-year medical students who participated in the clerkship during a 2-year
      time period. Results were summarized by three different combinations of prior
      clerkship experiences and overall. RESULTS: Students reported gains as a result
      of the clerkship for the majority of medical problems and procedures. However,
      there were differences in the clerkship's perceived contribution depending on the
      timing and sequence of clinical rotations. Even when the family medicine
      clerkship followed all other primary care rotations, students perceived that the
      clerkship contributed to gains in knowledge of undifferentiated and commonly seen
      problems; applications of health promotion, disease prevention, and patient
      education; importance of family dynamics in patient care; business aspects of
      medical practice; and appreciation of family practice. CONCLUSIONS: The results
      demonstrate how a required family medicine clerkship can enhance the clinical
      learning that occurs on other rotations. The study also demonstrates that it is
      possible to track a clerkship's contribution to student development and to
      understand how a clerkship's role may change according to students' prior
      experiences.

PMID- 9597531
TI  - Use of an objective structured clinical examination in evaluating student
      performance.
AB  - BACKGROUND AND OBJECTIVES: The objective structured clinical exam (OSCE) is
      increasingly being used to evaluate student clinical performance. However, scant
      literature exists pertinent to this approach in evaluating family medicine
      clerkship performance. In this study, we assess 8 years' experience with a family
      medicine clerkship OSCE. METHODS: Eight annual clerkship OSCEs and the
      performance of 696 students are described. Comparisons of faculty evaluation,
      written exam, and OSCE performance are made for 335 students. Post-OSCE student
      and faculty feedback regarding OSCE validity and utility is also presented.
      RESULTS: Student performance is highest in medical history taking and physical
      examination and lowest in information-sharing stations. OSCE results appear to be
      relatively consistent on a year-to-year basis. OSCE, faculty evaluation, and
      written exam results have low overall levels of correlation, particularly in
      assessing performance that differs substantially from the mean. Students and
      faculty agree that the OSCE experience reflects skills that students should
      possess, but there is less agreement that the OSCE reflects clerkship-related
      learning and actual student performance. Both students and faculty derive insight
      from the OSCE regarding the definition of specific learning needs. CONCLUSIONS:
      The family medicine clerkship OSCE we describe appears to provide consistent
      measures of student performance. Although content validity is high, further
      assessment is needed to assure construct validity. The OSCE experience provides
      students with a rich resource for defining clerkship-related learning needs.
      Study results strongly suggest that OSCEs, faculty evaluations, and written exams
      provide differing measures of student performance. The reasons for these
      differences merit further exploration.

PMID- 9597532
TI  - Integrating osteopathic training into family practice residencies.
AB  - BACKGROUND AND OBJECTIVES: Since the mid-1980s, the number of osteopathic
      graduates has increased, and the number of osteopathic hospitals has decreased.
      This has led to an increasing number of osteopathic students seeking training in
      Accreditation Council for Graduate Medical Education (ACGME) family practice
      residency programs. In response to these developments and to a declining pool of
      allopathic applicants in the early 1990s, at least 35 ACGME programs have
      completed the American Osteopathic Association (AOA) accreditation process as
      approved internship sites. This article describes 1) the rationale for becoming
      accredited, 2) the AOA accreditation process, 3) a model osteopathic curriculum,
      4) potential difficulties, 5) issues to consider in approaching a decision to
      become AOA accredited, and 6) future trends in osteopathic graduate medical
      education.

PMID- 9597533
TI  - Assessing colposcopic skills: the instructor's handbook.
AB  - BACKGROUND AND OBJECTIVES: In the United States, 93% of family practice residency
      programs teach colposcopy. Training should ideally include didactic teaching of
      basic knowledge, followed by practice on models and then supervised teaching with
      patients. Although various curricula have been published that outline basic
      principles of colposcopy education, methods of determining clinical competency
      among resident physicians are lacking. Methods of assessing psychomotor are
      cognitive skills in colposcopy are available for instructors, including the use
      of preclinical cervical practice models for colposcopic biopsy and endocervical
      curettage, visual skills tests that use images of colposcopic findings,
      colposcopy CD-ROMs, written pretest and posttest knowledge assessment
      instruments, and procedural checklists. Specific parameters for many of these
      tools can be used to define clinical competency in colposcopy.

PMID- 9597534
TI  - Predicting resident confidence to lead family meetings.
AB  - BACKGROUND AND OBJECTIVES: Family physicians frequently encounter patients'
      family members in family meetings regarding health care. Although residents are
      expected to learn how to interview families, no quantitative studies have
      examined variables associated with building residents' confidence in their
      ability to lead family meetings. The current study sought to clarify the
      relationship between a number of training, participant, and situational
      components and resident confidence. METHODS: All family practice residents (n =
      90) in a five-residency program system were sent a survey that examined their
      experience in and perceived competence to conduct family meetings. Responses were
      analyzed with a hierarchical regression analysis and an ex post facto univariate
      analysis. RESULTS: Residents with higher perceived confidence in their ability to
      run a family meeting were male, had specific training for leading family
      meetings, had participated in and initiated more family meetings, perceived
      stronger family physician faculty support, and had more family systems training
      than lower-confidence residents. CONCLUSIONS: The results highlight the
      experiential, curricular, and environmental variables that are associated with
      building resident confidence to lead family meetings. Residents may benefit from
      early exposure to the skills needed for family meetings and from reinforcement of
      these skills through observations of skilled practitioners, the expectation that
      they will initiate meetings, and the opportunity to debrief meetings with
      supportive faculty. Family meeting curricula should include conflict management
      skills and incorporate input from other specialists and hospital personnel who
      meet with families.

PMID- 9597535
TI  - Validity of the medical outcomes study depression screener in family practice
      training centers and community settings.
AB  - BACKGROUND AND OBJECTIVES: Screening inventories that identify primary care
      patients suffering from depression should be brief, correlate with depression
      diagnoses, and be evaluated in populations with whom the inventories will be
      used. METHODS: A total of 566 patients from a medical school training center and
      457 patients from six community family practice offices completed the Medical
      Outcomes Study (MOS) depression screener and a questionnaire reporting
      demographic information and health habits. All subjects scoring above the
      recommended screener cut-off, and a random sample of those scoring below, were
      interviewed with the Diagnostic Interview Schedule (DIS). RESULTS: A total of 195
      subjects from the training center and 147 from the community sample were called
      and administered the DIS. About 33% of the training center and 25% of the
      community sample scored above the cutoff. Of those above the cutoff and
      administered the DIS, 23% of the training center and 10% of the community sample
      were diagnosed with either major depression or dysthymia. CONCLUSIONS: The MOS
      screener was an effective method of identifying depressed subjects in the
      training center and community settings. However, because of the relatively low
      prevalence of depression in these settings, a relatively high number are falsely
      screened positive. Identifying these patients as having subthreshold depressive
      symptoms and the necessity/efficacy of treatment is controversial, as is the use
      of screening instruments. The simplified MOS scoring strategy and template used
      in this study would probably increase its usefulness in the primary care setting.

PMID- 9597536
TI  - Prevalence of and factors associated with current and lifetime depression in
      older adult primary care patients.
AB  - BACKGROUND: Depression in late life is a significant health problem in the United
      States. This study examined the relationship between depression and alcohol,
      cigarette use, family history, and sociodemographic factors in older adult
      primary care patients. METHODS: As part of a larger clinical trial, 2,732
      patients in 24 primary care offices were recruited to complete a self
      administered health screening survey. Depression was assessed using Diagnostic
      and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R)
      criteria for lifetime and current depression. RESULTS: A total of 17.8% of
      females and 9.4% of males age 60 and over met DSM-III-R criteria for lifetime
      depression; 10.6% of the females and 5.7% of the males met current depression
      criteria. Depression was significantly and positively correlated with female
      gender and family history of mental health problems and negatively correlated
      with social contact. CONCLUSIONS: Older adults, especially women, should be
      considered at elevated risk for depression when a family history of mental health
      problems and self-report of inadequate social connection can be established.

PMID- 9597537
TI  - Russian family practice training program: a single step on a long journey.
AB  - BACKGROUND AND OBJECTIVES: Since 1992, when the Russian government recognized
      family practice as a medical specialty, efforts have begun to progress from the
      idea stage to the delivery of patient care via family practice methods. We
      describe an educational effort to help teach Russian physicians family practice
      skills. METHODS: Five young Russian physicians were selected from an initial pool
      of 15 candidates on the basis of standardized testing, English language skills,
      and their potential to teach future Russian family physicians. Clinical,
      teaching, and business curricula were developed and used during the 6-month
      training period for the five selected physicians. Trainees were evaluated by
      mentors' and preceptors' written evaluations and by the American Board of Family
      Practice In-training Examination before, during, and at completion of the
      training. Subsequently, a fully equipped family practice office was opened in St
      Petersburg to serve as an on-site training facility. RESULTS: The trainees' self
      perceived knowledge in community medicine, geriatrics, medical decision making,
      patient education, behavioral science, preventive medicine, and general family
      practice topics improved over the course of training. The composite scores on the
      in-training examinations improved from baseline (30 versus 308). Preceptors noted
      the greatest improvements in the use of clinical instruments, proficiency in
      physical exams, accessing medical information, and formulating differential
      diagnoses. The St Petersburg family practice office opened on October 1, 1996.
      The trainees now participate in the care of patients in this office and teach a
      new class of family medicine interns. CONCLUSION: The training program we
      describe has allowed Russian physicians to acquire new skills and knowledge that
      they can use and adapt to training future Russian family physicians.

PMID- 9597538
TI  - Motivating change: a missiological model.

PMID- 9597539
TI  - Additional empirical relationships between oligosaccharide structure and high pH
      anion exchange chromatography.

PMID- 9597540
TI  - Production and characterization of a monoclonal antibody able to discriminate
      galectin-1 from galectin-2 and galectin-3.
AB  - Antisera raised against galectin-1 exhibit crossreactivities with other galectins
      or related molecules. In order to overcome this problem, a monoclonal antibody to
      human brain galectin-1 was obtained by selecting clones without reactivity toward
      galectin-3. This mAb specifically bound galectin-1 of various animal origins but
      neither galectin-2 nor galectin-3. Western-blotting analysis of soluble human
      brain extracts after 2D gel electrophoresis revealed only the two most acidic
      isoforms of galectin-1. The ability of this mAb to bind galectin-1/asialofetuin
      complexes indicates that its epitope is not localized in the carbohydrate
      recognition domain of galectin-1. This particularity induces with efficiency its
      monospecificity.

PMID- 9597541
TI  - Differential recognition by proteins of alpha-galactosyl residues on endothelial
      cell surfaces.
AB  - The binding of proteins to cell surface carbohydrates contributes to cell-cell
      interactions in development, immunity, and various physiologic processes. Such
      interactions are presumably dictated not only by the chemical structure of the
      carbohydrate but also reflect the properties of the protein and the
      microenvironment in which the protein-carbohydrate interaction occurs. To explore
      the factors influencing the recognition of cell surface carbohydrates by
      proteins, the extent to which three classes of proteins--anti-Gal alpha 1-3Gal
      IgM found in higher primates, Griffonia simplicifolia type I lectin, isolectin B4
      (GS-IB4), and alpha-galactosidase--interact with Gal alpha 1-3Gal on porcine cell
      surfaces was tested. Although the Gal alpha 1-3Gal residues expressed on porcine
      endothelial cells and recognized by anti-Gal alpha 1-3Gal IgM and GS-IB4 were
      both sensitive to cleavage by alpha-galactosidase, the sites recognized by GS-IB4
      were more sensitive to cleavage than sites recognized by anti-Gal alpha 1-3Gal
      IgM. Cross-blocking studies on porcine cell surfaces revealed that a significant
      proportion of anti-Gal alpha 1-3Gal IgM bound to sites not recognized by GS-IB4;
      however, anti-Gal alpha 1-3Gal IgM and GS-IB4 recognized the same sites on
      solubilized membrane proteins and model compounds. These results suggest that
      features of the cell surface such as the three-dimensional arrangement of Gal
      alpha 1-3Gal and characteristics of the protein such as size and valency play
      critical roles in specific interactions on cell surfaces.

PMID- 9597542
TI  - A high-throughput microscale method to release N-linked oligosaccharides from
      glycoproteins for matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometric analysis.
AB  - This report describes a convenient method for the rapid and efficient release of
      N-linked oligosaccharides from low microgram amounts of glycoproteins. A 96-well
      MultiScreen assay system containing a polyvinylidene difluoride (PVDF) membrane
      is employed to immobilize glycoproteins for subsequent enzymatic deglycosylation.
      Recombinant tissue-type plasminogen activator (rt-PA) is used to demonstrate the
      deglycosylation of 0.1-50 micrograms of a glycoprotein. This method enabled the
      recovery of a sufficient amount of N-linked oligosaccharides released
      enzymatically with peptide N-glycosidase F (PNGaseF) from as little as 0.5
      microgram rt-PA for subsequent analysis by matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The
      immobilization of rt-PA to the PVDF membrane did not sterically inhibit the
      PNGaseF-mediated release of oligosaccharides from rt-PA as determined by tryptic
      mapping experiments. Comparison of the oligosaccharides released from 50
      micrograms of rt-PA by either the 96-well plate method or by a standard solution
      digestion procedure showed no significant differences in the profiles obtained by
      high-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC
      PAD). Both neutral and sialylated oligosaccharide standards spiked into wells
      were recovered equally as determined by HPAEC-PAD. One advantage of this approach
      is that reduction and alkylation can be performed on submicrogram amounts of
      glycoproteins with easy removal of reagents prior to PNGaseF digestion. In
      addition, this method allows 60 glycoprotein samples to be deglycosylated in 1
      day with MALDI-TOF or HPAEC-PAD analysis being performed on the following day.

PMID- 9597543
TI  - The ALG10 locus of Saccharomyces cerevisiae encodes the alpha-1,2
      glucosyltransferase of the endoplasmic reticulum: the terminal glucose of the
      lipid-linked oligosaccharide is required for efficient N-linked glycosylation.
AB  - The biosynthesis of the lipid-linked oligosaccharide substrate for N-linked
      protein glycosylation follows a highly conserved pathway at the membrane of the
      endoplasmic reticulum. Based on the synthetic growth defect in combination with a
      reduced oligosaccharyltransferase activity (wbp1), we have identified alg10
      mutant strains which accumulate lipid-linked Glc2Man9GlcNAc2. We cloned the
      corresponding wild-type gene and show in a novel in vitro assay that Alg10p is a
      dolichyl-phosphoglucose-dependent glucosyltransferase which adds the terminal
      alpha-1,2 glucose to the lipid-linked Glc2Man9GlcNAc2 oligosaccharide.
      Hypoglycosylation of secreted proteins in alg10 deletion strains demonstrates
      that the terminal alpha-1,2-linked glucose residue is a key element in substrate
      recognition by the oligosaccharyltransferase. This ensures that primarily
      completely assembled oligosaccharide is transferred to protein.

PMID- 9597544
TI  - Structural comparison of fibroblast growth factor-specific heparan sulfates
      derived from a growing or differentiating neuroepithelial cell line.
AB  - Heparan sulfate (HS) glycosaminoglycans are essential modulators of fibroblast
      growth factor (FGF) activity both in vivo and in vitro, and appear to act by
      cross-linking particular forms of FGF to appropriate FGF receptors. We have
      recently isolated and characterized two separate HS pools derived from
      immortalized embryonic day 10 mouse neuroepithelial 2.3D cells: one from cells in
      log growth phase, which greatly potentiates the activity of FGF-2, and the other
      from cells undergoing contact-inhibition and differentiation, which
      preferentially activates FGF-1. These two pools of HS have very similar
      functional activities to those species isolated from primary neuroepithelial
      cells at corresponding stages of active proliferation or differentiation. We
      present here a structural comparison between these cell line HS species to
      establish the nature of the changes that occur in the biosynthesis of HS. A
      combination of chemical and enzymatic cleavage, low pressure chromatography and
      strong anion-exchange HPLC were used to generate full chain models of each
      species. Overall, the HS pools synthesized in the dividing cell line pools
      possessed less complex sulfation than those derived from more differentiated,
      growth arrested cells.

PMID- 9597545
TI  - Stable expression of mammalian beta 1,4-galactosyltransferase extends the N
      glycosylation pathway in insect cells.
AB  - An established lepidopteran insect cell line (Sf9) was cotransfected with
      expression plasmids encoding neomycin phosphotransferase and bovine beta 1,4
      galactosyltransferase. Neomycin-resistant transformants were selected, assayed
      for beta 1,4-galactosyltransferase activity, and the transformant with the
      highest level of enzymatic activity was characterized. Southern blots indicated
      that this transformed Sf9 cell derivative contained multiple copies of the
      galactosyltransferase-encoding expression plasmid integrated at a single site in
      its genome. One-step growth curves showed that these cells supported normal
      levels of baculovirus replication. Baculovirus infection of the transformed cells
      stimulated beta 1,4-galactosyltransferase activity almost 5-fold by 12 h
      postinfection. This was followed by a gradual decline in activity, but the
      infected cells still had about as much activity as uninfected controls as late as
      48 h after infection and they were able to produce a beta 1,4-galactosylated
      virion glycoprotein during infection. Infection of the transformed cells with a
      conventional recombinant baculovirus expression vector encoding human tissue
      plasminogen activator also resulted in the production of a galactosylated end
      product. These results demonstrate that stable transformation can be used to add
      a functional mammalian glycosyltransferase to lepidopteran insect cells and
      extend their N-glycosylation pathway. Furthermore, stably-transformed insect
      cells can be used as modified hosts for conventional baculovirus expression
      vectors to produce foreign glycoproteins with "mammalianized" glycans which more
      closely resemble those produced by higher eucaryotes.

PMID- 9597546
TI  - Transcriptional and posttranscriptional regulation of alpha 1,3
      galactosyltransferase in activated endothelial cells results in decreased
      expression of Gal alpha 1,3Gal.
AB  - Gal alpha 1,3Gal carbohydrate residues are present in the glycoproteins and
      glycolipids of lower mammals, and appear to be involved in the binding
      specificity of several membrane receptors. We report here that endothelial cells
      stimulated with lipopolysaccharide or inflammatory cytokines modulate their
      expression of UPD-Gal: beta-D-Gal alpha 1,3-galactosyltransferase (alpha 1,3GT),
      the Golgi enzyme that attaches a galactose in alpha 1,3 configuration to an N
      acetyllactosamine acceptor. Upon activation, the steady state level of mRNA is
      transiently increased, the modifications being paralleled by a transcriptional
      regulation of the gene. Cell-associated enzyme activity, on the other hand, falls
      rapidly after activation, before being up- and downregulated with kinetics that
      parallel those of the mRNA, and after 3 days reaches a level representing 40-60%
      of the activity in cells before activation. Overall Gal alpha 1,3Gal expression
      at the cell surface follows enzyme activity, except that it is insensitive to the
      rapid and transient reduction of activity occurring shortly after activation.
      This reduced alpha 1,3GT activity in stimulated EC is correlated with lower
      stability of the protein, and with a switch in the expression of the isoform
      pattern, isoform 1 being predominant in resting cells whereas after activation it
      is isoform 2 that predominates. The two isoforms, however, appear to have similar
      intrinsic stability, so that the reduced stability of the enzyme in activated EC
      probably results from an induced proteolytic degradation pathway.

PMID- 9597547
TI  - Mouse chondroitin 6-sulfotransferase: molecular cloning, characterization and
      chromosomal mapping.
AB  - Chondroitin 6-sulfotransferase (C6ST) catalyzes the transfer of sulfate from 3'
      phosphoadenosine 5'-phosphosulfate to position 6 of the N-acetylgalactosamine
      residue of chondroitin. Using chick C6ST cDNA as a probe, we cloned the cDNA of
      mouse C6ST. The mouse enzyme was predicted to be composed of 472 amino acids, and
      exhibited 71% sequence identity with the chicken enzyme. The mouse and chicken
      catalytic domains exposed to the luminal side exhibited 81% identity, while the
      homology of the remaining regions was less. Transfection and expression of the
      mouse cDNA in COS-7 cells yielded C6ST activity. Keratan sulfate sulfotransferase
      activity, which was simultaneously expressed, amounted to 3% of the C6ST
      activity, this value being significantly lower than that observed in the case of
      the chicken enzyme. Mouse C6ST mRNA was strongly expressed in the spleen, lung,
      and eye. In situ hybridization revealed that the transcript was localized in
      stromal cells in the marginal zone and red pulp of the spleen, and stromal cells
      in the bone marrow. Fluorescence in situ hybridization analysis revealed the gene
      is located in mouse chromosome 9.

PMID- 9597548
TI  - Structural characterization of the oligosaccharides of a human monoclonal anti
      lipopolysaccharide immunoglobulin M.
AB  - The oligosaccharide side chains of a human anti-lipopolysaccharide IgM produced
      by a human-human-mouse heterohybridoma were analyzed at each of its five
      conserved N-glycosylation sites. This antibody also has a potential sixth N
      glycosylation site in the variable region of its heavy chain which is not
      glycosylated. The oligosaccharides were released by digestion with various endo-
      and exoglycosidases and analyzed by matrix-assisted laser desorption/ionization
      time of flight mass spectrometry and fluorophore-assisted carbohydrate
      electrophoresis. The antibody has various complex- and hybrid-type
      oligosaccharide structures at Asn 171, various sialylated complex-type
      oligosaccharides at Asn 332 and 395, and high-mannose-type oligosaccharides at
      Asn 402 and 563. Of note is the presence in this human IgM of oligosaccharides
      containing N-glycolylneuraminic acid and N-acetylneuraminic acid in the ratio of
      98:2 as determined using anion-exchange chromatography. Furthermore, we observed
      oligosaccharide structures containing Gal alpha (1,3)Gal that have not been
      reported as components of human glycoproteins.

PMID- 9597549
TI  - Further characterization of the binding of human recombinant interleukin 2 to
      heparin and identification of putative binding sites.
AB  - We have previously provided compelling evidence that human recombinant
      interleukin 2 (IL-2) binds to the sulfated polysaccharides heparin, highly
      sulfated heparan sulfate and fucoidan. Here we show that IL-2 binding is
      dependent on heparin chain length, but with fragments as small as 15-mers
      retaining binding activity. The addition of exogenous heparin has no effect on
      the in vitro biological activity of IL-2. In addition soluble IL-2 receptor alpha
      and beta polypeptides do not compete with heparin for the binding of IL-2. IL-2
      bound by heparin is still recognized by two IL-2 specific monoclonal antibodies,
      3H9 and H2-8, whose epitopes lie in the amino terminal region. Murine IL-2 unlike
      its human counterpart fails to bind to heparin. Human IL-2 analogs with single
      amino acid substitutions at positions Lys43, Thr51, and Gln126 analogs no longer
      bind to heparin. By contrast the Arg38Ala analog retains heparin full heparin
      binding activity. These experimental findings together with molecular modeling
      studies suggest two putative heparin binding sites on human IL-2, one involving
      four basic residues, Lys48, Lys49, Lys54, and His55, and the other being a
      discontinuous site comprising Lys43, Lys64, Arg81, and Arg83. Neither of these
      two clusters is completely conserved in murine IL-2. Overall our data suggest
      that the binding of human IL-2 to heparin and heparan sulfate does not interfere
      with IL-2/IL-2 receptor interactions. Therefore, binding to glycosaminoglycan may
      be a mechanism for retaining the cytokine in an active form close to its site of
      secretion in the tissue, thus favoring a paracrine role for IL-2.

PMID- 9597550
TI  - The expanding beta 4-galactosyltransferase gene family: messages from the
      databanks.
AB  - From a systematic search of the UniGene and dbEST databanks, using human beta 4
      galactosyltransferase (beta 4GalT-I), which is recognized to function in lactose
      biosynthesis, as the query sequence, we have identified five additional gene
      family members denoted as beta 4GalT-II, -III, -IV, -V, and -VI. Complementary
      DNA clones containing the complete coding regions for each of the five human
      homologs were obtained or generated by a PCR-based strategy (RACE) and sequenced.
      Relative to beta 4GalT-I, the percent sequence identity at the amino acid level
      between the individual family members, ranges from 33% (beta 4GalT-VI) to 55%
      (beta 4GalT-II). The highest sequence identity between any of the homologs is
      between beta 4GalT-V and beta 4GalT-VI (68%). beta 4GalT-II is the ortholog of
      the chicken beta 4GalT-II gene, which has been demonstrated to encode an alpha
      lactalbumin responsive beta 4-galactosyltransferase (Shaper et al., J. Biol.
      Chem., 272, 31389-31399, 1997). As established by Northern analysis, beta 4GalT
      II and -IV show the most restricted pattern of tissue expression. High steady
      state levels of beta 4GalT-II mRNA are seen only in fetal brain and adult heart,
      muscle, and pancreas; relatively high levels of beta 4GalT-VI mRNA are seen only
      in adult brain. When the corresponding mouse EST clone for each of the beta 4GalT
      family members was used as the hybridization probe for Northern analysis of
      murine mammary tissue, transcription of only the beta 4GalT-I gene could be
      detected in the lactating mammary gland. These observations support the
      conclusion that among the six known beta 4GalT family members in the mammalian
      genome, that have been generated through multiple gene duplication events of an
      ancestral gene(s), only the beta 4GalT-I ancestral lineage was recruited for
      lactose biosynthesis during the evolution of mammals.

PMID- 9597551
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1996), III.
      Secular changes in susceptibility].
AB  - Susceptibilities to various antimicrobial agents were examined for Enterococcus
      faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp., and
      Pseudomonas aeruginosa that were isolated from patients with urinary tract
      infections (UTIs) in 10 hospitals during June 1996 to May 1997, and the results
      were compared with those obtained during the same period in earlier years. 1. E.
      faecalis Among E. faecalis strains, those with high susceptibilities to
      ampicillin and minocycline appeared to have decreased in the latest study period.
      2. S. aureus To almost antimicrobial agents, S. aureus isolated from
      uncomplicated UTIs showed low susceptibilities. But the MIC50s of those agents
      for S. aureus from complicated UTIs have changed better state. Particularly, the
      MIC50s of imipenem and clindamycin were 0.125 microgram/ml or below in the latest
      period for the first time in our history. 3. E. coli The susceptibilities to
      piperacillin and quinolones of E. coli isolated from uncomplicated UTIs were
      better than those isolated from complicated UTIs. 4. Klebsiella spp. The
      susceptibilities to almost antimicrobial agents of Klebsiella spp. have been
      better during the latest period, compared to those during period of 1995-1996,
      but to ofloxacin and ciprofloxacin have appeared to have been lower. 5. P.
      aeruginosa The susceptibilities to quinolones of P. aeruginosa have been better
      during the latest period compared those during periods of 1995-1996. But, the
      susceptibilities to cefozopran, carbapenems and monobactams of P. aeruginosa
      isolated from complicated UTIs appeared to have been lower. These susceptibility
      changes should be utilized in determining clinical treatments.

PMID- 9597552
TI  - [Mechanism of vancomycin resistance in MRSA strain Mu50].
AB  - The mechanism of vancomycin resistance in methicillin-resistant Staphylococcus
      aureus (MRSA) Mu50 was investigated. More than 3 times increase of the
      incorporation of 14C-GluNAc into the cell wall of Mu50 was observed compared to
      those of vancomycin-susceptible strains FDA209P, H-1, LR5P1. The amount of
      cytoplasmic murein-monomer precursor increased more than 3 times in Mu50 compared
      to those of control strains. There was an increased production of PBP1, PBP2, and
      PBP2', which were 1.51, 17.2, and 7.06 times greater, respectively, in Mu50 than
      those in H-1, and 2.38, 4.46, and 1.96 times greater respectively, than those in
      LR5P1. By transmission electromicrograph, it was shown that the cell wall of Mu50
      was twice thicker than that of LR5P1. Increase of tightly-bound vancomycin to the
      cell wall fraction was observed in Mu50 when compared to those in FDA209P and H-1
      strains. From these results, the increase of the vancomycin targets, free D-Ala-D
      Ala residues in the cell wall, in number, due to the activated cell wall
      synthesis, and/or decrease of the cross-linkage of the cell wall was suggested to
      be the mechanism of vancomycin resistance in the Mu50 strain.

PMID- 9597553
TI  - Fenoldopam: a new dopamine agonist for the treatment of hypertensive urgencies
      and emergencies.
AB  - Fenoldopam is a selective dopamine agonist that is being considered for the
      parenteral treatment of systemic hypertension. In both an oral and parenteral
      form, the drug causes peripheral vasodilation by stimulating dopamine-1
      adrenergic receptors. Its pharmaco-dynamics are reviewed in this article, along
      with the clinical experiences in patients with hypertensive urgencies and
      emergencies. Intravenous fenoldopam may provide advantages over sodium
      nitroprusside because it can induce both a diuresis and natriuresis, is not light
      sensitive, and is not associated with cyanide toxicity. There is no evidence for
      rebound hypertension after discontinuation of fenoldopam influsion.

PMID- 9597554
TI  - Single-dose pharmacokinetics and pharmacodynamics of alprazolam in elderly and
      young subjects.
AB  - The pharmacokinetics and pharmacodynamics of the benzodiazepine anxiolytic
      alprazolam (1 mg orally) were compared between young and elderly healthy
      volunteers. Eight young subjects (mean age 29.8 years) and eight elderly
      volunteers (mean age 68.4 years) received oral placebo and alprazolam (1.0 mg) in
      a randomized, double-blind, single-dose crossover study. In the elderly subjects,
      plasma concentrations were higher, although not significantly so, than in young
      volunteers 0.25, 0.5, and 0.75 hours after dosage. Apparent elimination half
      life, time of maximum concentration, maximum concentration, volume of
      distribution, and apparent clearance were similar for the two groups. In both
      groups, alprazolam treatment (versus placebo) produced significant changes in
      typical benzodiazepine agonist effects, such as increased sedation and fatigue,
      reduced excitement, increased feelings of spaciness, and perception of thinking
      slowed. For some measures, the alprazolam-placebo difference was greater in young
      than in elderly subjects. In both groups, alprazolam significantly impaired
      performance on the digit-symbol substitution test (DSST). EEG studies indicated
      significant increases in relative beta amplitude (13-30 Hz range) after
      alprazolam compared to placebo. Percent DSST decrement and percent EEG change
      were highly correlated with plasma alprazolam concentrations for both groups.
      There were modest increases in alprazolam plasma concentration in the elderly
      compared to the younger group shortly after drug administration, but there was no
      evidence of increased sensitivity to the pharmacodynamic effects of alprazolam in
      the elderly.

PMID- 9597555
TI  - Plasma nitric oxide before and after smoking cessation with nicotine nasal spray.
AB  - Nicotine may affect cardiovascular function through release of neurotransmitters
      from autonomic nerves or release of vasoactive substances from the vascular
      endothelium. Nitric oxide is a neurotransmitter and endothelium-derived factor
      that reduces tone of vascular smooth muscle. Experiments were designed to
      determine whether or not use of nicotine nasal spray for smoking cessation
      affects plasma levels of nitric oxide. Forty smokers self-administered nicotine
      by nasal spray (one 0.5 mg spray to each nostril). Blood samples were taken
      before the use of the nasal spray and at treatment day 7 for the measurement of
      cotinine by high pressure liquid chromatography and nitric oxide (NOx) by
      chemiluminescence. Age-comparable controls were never-smokers nonnicotine users
      recruited from laboratory personnel. Mean plasma concentrations of NOx from
      smokers before treatment were significantly greater compared with nonsmokers (23
      +/- 10, n = 40 and 15 +/- 6, n = 13 nmoles/mL [mean +/- SD], respectively, P <
      0.01). Plasma NOx in smokers was not significantly correlated with the average
      daily number of cigarettes smoked (r2 = 0.02, P > 0.05) but was positively and
      linearly correlated with plasma cotinine (r2 = 0.13, P < 0.02). In 32 self
      reported abstinent smokers (confirmed by expired carbon monoxide < 9 ppm) using
      nicotine nasal spray, cotinine decreased by 64% from pretreatment levels of 284
      +/- 103 to posttreatment levels of 90 +/- 58 ng/mL. Plasma NOx was unchanged and
      went from 23.0 +/- 10.1 at pretreatment to 21 +/- 12 nmoles/mL with nicotine
      treatment. These results suggest that nicotine-use, independent of cigarette
      smoking, affects plasma NOx.

PMID- 9597556
TI  - The effects of renal impairment on the pharmacokinetics of zalcitabine.
AB  - The pharmacokinetics of zalcitabine (ddC) were studied in three groups of
      subjects with varying degrees of renal function: group I (n = 5), creatinine
      clearance (Clcr) 0-10 mL/min; group II (n = 10), Clcr 11-50 mL/min; and group III
      (n = 8), Clcr > 50 mL/min. Each patient received a single 0.75-mg oral dose of
      zalcitabine, and multiple blood and urine samples were collected over a 10-hour
      period after administration. Plasma and urine concentrations of zalcitabine were
      measured by high-performance liquid chromatography. No statistically significant
      differences were observed between the three groups in maximum concentration
      (Cmax), time to Cmax (tmax), or volume of distribution (V/F). Also, elimination
      half-life (t1/2), area under the concentration-time curve (AUC0-10), total body
      clearance (Cl/F), elimination rate constant (Ke), and renal clearance (Clr) did
      not differ significantly between the two groups with renal impairment (groups I
      and II). However, there was a significant difference in these parameters between
      groups with renal impairment (I and II) and group III. A linear correlation was
      observed between creatinine clearance (Clcr) and Clr, Ke, and Cl/F in all
      subjects. Clearance of zalcitabine is decreased after a single oral dose in
      patients with renal impairment. Dosage adjustment may be warranted in such
      patients, especially in those with severe renal impairment.

PMID- 9597557
TI  - A dose proportionality study of eprosartan in healthy male volunteers.
AB  - The present study investigated the proportionality of exposure after single oral
      doses of 100, 200, 400, and 800 mg of eprosartan, a nonpeptide, nonbiphenyl
      angiotensin II receptor antagonist, in 23 healthy young men. Eprosartan was safe
      and well tolerated. Exposure to eprosartan increased with dose but in a less than
      proportional manner. For each two-fold dose increase, area under the
      concentration--time curve (AUC) increased an average of 1.6 to 1.8 times and
      maximum plasma drug concentration (Cmax) increased an average of 1.5 to 1.8
      times. For both parameters, the greatest difference from the dose multiple was
      observed between the 400- and 800-mg doses. Dose proportionality of eprosartan,
      as assessed by an equivalence-type approach using the 100-mg dose as the
      reference and a 30% acceptance region (0.70, 1.43), was achieved for the 200- and
      400-mg doses for AUC and the 200-mg dose for Cmax. The observed changes in the
      pharmacokinetics of eprosartan suggest slight saturation of absorption of
      eprosartan over the 100- to 800-mg dose range, most likely due to the
      physicochemical properties of the drug (pH-dependent aqueous solubility and
      lipophilicity).

PMID- 9597558
TI  - Pharmacokinetics and safety of a novel recombinant soluble human thrombomodulin,
      ART-123, in healthy male volunteers.
AB  - The safety and pharmacokinetics of a novel recombinant soluble human
      thrombomodulin, ART-123 were evaluated in single- and multiple-dose studies
      involving 16 healthy male volunteers. ART-123 was administered by intravenous
      infusion over 2 hours. The single-dose study indicated that plasma ART-123 levels
      at doses of 0.03, 0.1, and 0.3 mg declined biexponentially and those half-lives
      were approximately 4 hours (t1/2 alpha) and 20 hours (t1/2 beta), respectively.
      The mean plasma peak concentration and area under the plasma concentration-time
      curves increased in proportion to the given doses. Mean urinary recovery within
      the first 48 hours was between 54.3% and 59.8% of dose. In the multiple-dose
      study, ART-123 was administered at a dose of 0.2 mg once daily for 3 days. ART
      123 did not accumulate as judged from plasma concentrations and urinary recovery.
      There were no abnormal findings in objective symptoms and laboratory findings,
      including blood pressure, heart rate, electrocardiogram, body temperature,
      hematology, bleeding time, coagulation and hemostatic parameters, blood
      chemistry, and urinalysis. There were no significant adverse reactions or
      abnormalities in physical and laboratory examinations that could definitely be
      attributed to the drug at a dose of 0.3 mg as a single administration and at a
      dose of 0.2 mg once daily for 3 days. These results indicate that ART-123 is safe
      at doses up to 0.2 mg once daily for 3 days and may have clinical application.
      Further studies are needed, however, to evaluate the safety and pharmacokinetics
      of ART-123 in the targeted population.

PMID- 9597559
TI  - A phase I double-blind, placebo-controlled, single rising dose study to determine
      the safety, tolerability, and pharmacokinetics of oral YM934 in healthy male
      volunteers.
AB  - In this phase I study a novel potassium channel opener (YM934) was administered
      to young healthy male volunteers to identify a dose with minimal cardiovascular
      effects. The study was carried out using a double-blind, placebo-controlled
      rising dose design with oral YM934 in single doses of 20 micrograms, 60
      micrograms, and 180 micrograms. During each study day frequent blood samples were
      obtained for drug assay, measurements of cardiovascular parameters, and
      parasympathetic activity. The drug was well tolerated, with headache being the
      only significant adverse event. No relationship could be detected between dose or
      plasma concentration of YM934 and headache. No significant changes in routine
      laboratory and pharmacodynamic parameters occurred between placebo and active
      drug treatment. The pharmacokinetics of YM934 were characterized by a rapid oral
      absorption, an elimination half-life of 30 hours, and an oral clearance of 1.7
      L/h. The obtained data allow estimation of a YM934 dose regimen with minimal
      cardiovascular (side) effects to be used for future efficacy studies.

PMID- 9597560
TI  - Bioequivalence assessment of a single 5 mg/day testosterone transdermal system
      versus two 2.5 mg/day systems in hypogonadal men.
AB  - A novel, nonscrotal, transdermal delivery system for testosterone therapy has
      been marketed for treatment of hypogonadal men. The usual dose of this system is
      two 2.5 mg/day systems applied daily. A new system has been developed that
      administers a dose of 5 mg/day using a single patch rather than two patches. A
      randomized, steady-state, four-period, replicate-design, open-label, crossover
      study was conducted to assess the bioequivalence of the two testosterone
      transdermal delivery systems in postpubertal, hypogonadal men: two 2.5 mg/day
      patches as the reference regimen (R) and one 5 mg/day patch as the test regimen
      (T). 21 men were enrolled, and 20 completed the study. Each subject was randomly
      assigned to one of four sequences (R1-R2-T1-T2, T1-T2-R1-R2, R1-T1-T2-R2, T1-R1
      R2-T2), such that each subject received each regimen during two study sessions.
      Two subjects were inadvertently treated according to the sequence T1-R1-T2-R2.
      Patches were applied to the upper arm, thigh, and back in the evening on days 1,
      2, and 3, respectively, of each study session. Serial blood samples were obtained
      for pharmacokinetic analysis of testosterone for 24 hours after patch application
      on day 3 of each study session. The two formulations would be considered
      bioequivalent if the 90% confidence intervals (CI) for the ratios of the adjusted
      geometric means for T:R for both area under the concentration--time curve from 0
      to 24 hours (AUC0-24) and maximum concentration (Cmax) were completely contained
      in the interval (0.80, 1.25). Mean values for AUC0-24 and Cmax were similar for
      the two formulations. The T and R formulations were found to be bioequivalent
      based on both AUC0-24 (90% CI 0.96, 1.08) and Cmax (90% CI 0.92, 1.07). The
      median time to Cmax was also similar, indicating comparable rates of testosterone
      absorption for both formulations. Based on this analysis, the testosterone
      transdermal system 5 mg/day patch is bioequivalent to two of the 2.5 mg/day
      patches. Both systems were safe and well tolerated in hypogonadal men.

PMID- 9597561
TI  - Multiple-dose pharmacokinetics and pharmacodynamics of OROS and immediate-release
      amitriptyline hydrochloride formulations.
AB  - The pharmacokinetics and pharmacodynamics of amitriptyline hydrochloride after
      oral administration of an OROS osmotic system, which provides controlled drug
      delivery, and an immediate-release (IR) tablet, were evaluated in 24 healthy
      volunteers after repeated administration for 14 days. Each morning, subjects
      received either 75 mg of the OROS (amitriptyline HCl) controlled-release
      formulation or the 75 mg IR amitriptyline tablet for 14 days on two separate
      occasions with a washout period of 21 days according to a randomly assigned
      sequence. Serial blood samples were collected for a period of 58 hours after the
      day 14 dose, then these samples were analyzed by the gas chromatography method
      for amitriptyline and nortriptyline. Subjective ratings of dry mouth and
      drowsiness were collected at specific times throughout each treatment period.
      Administration of the OROS formulation resulted in much more consistent plasma
      concentrations of the drug and metabolite compared with the IR formulation at
      steady state. The mean maximum concentration (Cmax) of amitriptyline was
      significantly lower after administration of OROS than the IR formulation. Mean
      values for area under the concentration--time curve (AUC0-24) for the OROS and IR
      formulations were 1,265 and 1,393 ng. hr/mL, respectively. The drug-to-metabolite
      ratio was found to be similar for both treatments, suggesting that there was no
      difference in metabolism between treatments. Incidence and severity of the
      anticholinergic effects were similar for the two treatments. A clockwise
      hysteresis between baseline-corrected drowsiness and drug concentration suggests
      development of tolerance of the anticholinergic effects after both treatments.
      Using a hypothetical anatagonist metabolite model to explain tolerance
      development, the shape of the hysteresis curves of the two treatments could be
      explained by differences in dosing frequency.

PMID- 9597562
TI  - Short-term effects of nicardipine and propranolol on ocular and systemic
      hemodynamics in healthy Japanese subjects.
AB  - Ocular perfusion is a critical factor in ischemic ocular diseases, and blood flow
      in the ophthalmic artery has a pronounced effect on perfusion. To evaluate the
      effects of dihydropyridine calcium channel blocker and nonselective beta
      adrenergic antagonist on ocular perfusion, we investigated the short-term effects
      of single oral doses of nicardipine (40 mg) and propranolol (40 mg) on the blood
      flow velocity in the ophthalmic artery, intraocular pressure (IOP), systemic
      blood pressure, and heart rate in nine healthy Japanese male volunteers in a
      double-blind, placebo-controlled study using color Doppler imaging. Parameters
      were evaluated before and 60 and 120 minutes after administration. Nicardipine
      significantly increased the maximum systolic velocity and time-averaged blood
      flow velocity compared with placebo without significant increase in the
      resistance index. Propranolol had no significant effects on Doppler parameters.
      Propranolol exhibited a great reduction in IOP from placebo values. Systolic
      blood pressure and heart rate were significantly reduced by propranolol.
      Nicardipine significantly increased heart rate. These results suggest that
      nicardipine increased ophthalmic blood flow, but propranolol did not.

PMID- 9597563
TI  - Comparative efficacy and safety of controlled-release morphine suppositories and
      tablets in cancer pain.
AB  - Although the oral route is the preferred method of opioid therapy in patients
      with cancer pain, many patients will require an alternate route of analgesic
      administration at some point during the trajectory of their illness. This study
      compared the efficacy and safety of a novel, controlled-release suppository of
      morphine (MSC-R) and controlled-release morphine tablets (MSC-T) in patients with
      cancer pain. In a double-blind crossover study, 27 patients with cancer pain were
      randomized to receive MSC-R or MSC-T every 12 hours for 7 days each, using a 1:1
      analgesic equivalence ratio. Pain intensity was assessed using a visual analog
      scale (VAS) and the Present Pain Intensity Index of the McGill Pain
      Questionnaire. Nausea and sedation were also assessed with a VAS. Pharmacodynamic
      assessments were made by the patient at 8:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM
      and rescue morphine use recorded in a daily diary. There were no significant
      differences between MSC-R and MSC-T in overall scores for pain intensity VAS,
      ordinal pain intensity, and sedation. There was a small but significant
      difference in overall nausea VAS score in favor of MSC-R. Mean daily rescue
      analgesic use did not differ significantly during between treatment with MSC-R
      and MSC-T. MSC-R provides pain control comparable to that provided by MSC-T when
      given every 12 hours at a 1:1 dose ratio, and represents a reliable alternative
      method of pain control for patients unable to take oral opioid agents.

PMID- 9597564
TI  - Use of chlorzoxazone as an in vivo probe of cytochrome P450 2E1: choice of dose
      and phenotypic trait measure.
AB  - Chlorzoxazone is being developed and proposed for use as a probe to measure in
      vivo cytochrome P4502E1 activity, but the phenotypic trait measures that are used
      vary. Although the doses proposed for phenotyping range from 250 mg to 750 mg,
      the effect of dose on chlorzoxazone hydroxylation has not previously been
      evaluated. The purpose of this study was to characterize the pharmacokinetics of
      chlorzoxazone in normal healthy volunteers (N = 6) after single randomized oral
      doses of 250 mg and 750 mg. An additional 10 volunteers underwent a detailed
      pharmacokinetic study using the 250-mg dose to further evaluate proposed
      phenotypic trait measures (N = 16). Timed blood and urine samples were obtained
      for 10 hours for chlorzoxazone and 6-hydroxychlorzoxazone determination by HPLC.
      Pharmacokinetic parameter estimates were estimated using noncompartmental
      methods. Evaluation of phenotypic trait measures show that 6-hydroxychlorzoxazone
      to chlorzoxazone plasma concentration ratios at 2 to 4 hours after drug
      administration demonstrated the highest correlations with metabolite formation
      clearance (r = 0.9; P < 0.001). Urine-based parameters (e.g., total recovery)
      were not significantly related to formation clearance (r = 0.5; P > 0.05). Dose
      dependency in chlorzoxazone metabolism was shown by a 30% increase (P < 0.05) in
      the dose-normalized area under the concentration-time curve (AUC) of
      chlorzoxazone and lower incremental dose-normalized urinary recovery of 6
      hydroxychlorzoxazone at early timepoints after the 750-mg dose. In addition, the
      plasma ratio of 6-hydroxychlorzoxazone to chlorzoxazone at 4 hours was reduced by
      48% in 5 of 6 subjects after the 750-mg dose (P > 0.05). These data suggest that
      6-hydroxylation was saturated at the higher dose and illustrate the importance of
      dose selection in phenotyping. The results of this study indicate that a
      chlorzoxazone dose of 250 mg should be used and that a single plasma ratio
      obtained 2 to 4 hours after dosing is reflective of chlorzoxazone 6-hydroxylation
      and thus may serve as a cytochrome P4502E1 phenotypic trait measure.

PMID- 9597565
TI  - Levofloxacin does not alter cyclosporine disposition.
AB  - Certain fluoroquinolones have been shown to elevate the serum concentrations of
      the immunosuppressant cyclosporine. It is thus important to investigate the
      potential interaction between levofloxacin, a new fluoroquinolone antimicrobial
      agent, and the pharmacokinetics of cyclosporine. Twelve healthy subjects (6 men,
      6 women) were enrolled in and completed a placebo-controlled, randomized, double
      blind, two-phase crossover study. Subjects were given a single oral 10-mg/kg dose
      of cyclosporine solution during multiple-dose twice-daily oral treatment with
      placebo or 500 mg of levofloxacin. Blood cyclosporine concentrations were
      measured for 48 hours after each cyclosporine dose for pharmacokinetic
      evaluation. Cyclosporine pharmacokinetic parameters were comparable and not
      significantly different in the absence and presence of levofloxacin. Results of
      this study suggest that a clinically important pharmacokinetic interaction
      between levofloxacin and cyclosporine is unlikely to occur during concurrent
      therapy.

PMID- 9597566
TI  - Tumor evaluation and hematotherapy: what is the situation in 1998?

PMID- 9597567
TI  - A convergence of methods for a worldwide standard for CD34+ cell enumeration.

PMID- 9597568
TI  - Not all healthy donors mobilize hematopoietic progenitor cells sufficiently after
      G-CSF administration to allow for subsequent CD34 purification of the
      leukapheresis product.

PMID- 9597569
TI  - Antileukemic activity of TNF-alpha gene therapy with myeloid progenitor cells
      against minimal leukemia.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has exhibited antitumor activity against
      a variety of tumors in rodents and human tumor xenografts in nude mice, but it
      has been only marginally effective in cancer patients because of dose-limiting
      toxicity associated with systemic TNF-alpha therapy. To circumvent toxicity and
      to test the antileukemic activity against quantitated minimal leukemia, we have
      cloned human TNF-alpha (HuTNF-alpha) gene in an advanced myeloid progenitor cell
      line. 32Dcl3 myeloid progenitor cells transfected with HuTNF-alpha cDNA by the
      retroviral supernatant infection method stably express HuTNF-alpha gene and
      secrete substantial amounts of HuTNF-alpha. When injected i.v. into irradiated
      mice, transduced cells could be detected in the marrow but not in spleen or liver
      10-12 days later. Injection of 5 x 10(6) transduced cells produced no obvious
      symptoms of TNF-alpha toxicity (i.e., weight loss, cachexia, or fever) suggesting
      that TNF-alpha producing cells are well tolerated by the recipient mice.
      Coinjection of 5 x 10(6) transduced cells and 10(2) or 10(3) 32Dp210 leukemia
      (BCR/ABL+) cells resulted in inhibition of leukemia development by 10(2) but not
      10(3) 32Dp210 cells. An equal dose of nontransduced 32Dcl3 cells was ineffective
      in inhibiting leukemia progression by 10(2) 32Dp210 cells. Mice that rejected
      leukemia were BCR/ABL oncogene negative 8 weeks after leukemia cell injection.
      These data demonstrate the potential for TNF-alpha gene therapy for destroying
      residual leukemia, without the toxicity of systemic TNF-alpha therapy, following
      cytoreductive therapy and bone marrow transplant.

PMID- 9597570
TI  - Effect of stromal cell coculture on progenitor cell expansion and myeloid
      effector function in vitro.
AB  - Stimulation of CD34(+)-enriched marrow or light density marrow with various
      growth factor combinations can generate granulocyte progenitors and mature
      neutrophils in vitro. In this work, we have examined the influence of irradiated
      marrow stromal layers on growth factor-induced myeloid and early multipotential
      progenitor expansion from enriched marrow CD34+ progenitors. We have also
      explored whether the addition of early-acting growth factors known to enhance
      myelopoiesis in long-term culture, such as fibroblast growth factor (b-FGF),
      insulin growth factor (IGF-1), c-kit ligand or stem cell factor (SCF), and flk
      2flt-3 ligand (FL), can lengthen survival of CD34+ progenitors in these cultures.
      Stromal cell coculture resulted in greater numbers of total cells and CFU-GM at
      day 7 and day 14, but with the addition of multiple growth factors, these effects
      of stromal cell coculture were diminished. At day 14, generally < 1% of the
      expanded cells over stromal coculture conditions were CD34+, with up to 90%
      demonstrating CD15 positivity. Culture of CD34+ cells in the presence of early
      acting growth factors did not cause significant expansion of CD34+ cells over a
      14-day life span, even in the presence of marrow stromal cells. These data
      suggest that although stromal cell coculture for a period up to 14 days can
      enhance expansion of total cell numbers and CFU-GMs, stromal cell presence does
      not lead to expansion of CD34+ cells in these cultures and may diminish the
      number of clonogenic cells present when growth factors with differentiating
      capacity are present. Mature neutrophils harvested from such cultures are capable
      of chemotaxis, actin polymerization, and migration, suggesting a replete
      functional status.

PMID- 9597571
TI  - A randomized trial of two doses of cyclophosphamide with etoposide and G-CSF for
      mobilization of peripheral blood stem cells in 318 patients with stage II-III
      breast cancer.
AB  - The purpose of this study was to develop a less toxic outpatient chemotherapy
      regimen for mobilizing peripheral blood stem cells (PBSC). Three hundred eighteen
      patients with newly diagnosed stage II-III breast cancer who had received
      conventional dose adjuvant chemotherapy were randomized to receive intermediate
      dose cyclophosphamide (2 g/m2), etoposide (600 mg/m2), and granulocyte colony
      stimulating factor (G-CSF) 6 micrograms/kg/day (ID-Cy, n = 162) or high-dose
      cyclophosphamide (4 g/m2) and the same doses of etoposide and G-CSF (HD-Cy, n =
      156) followed by collection of PBSC. Three hundred seventeen of 318 patients had
      apheresis performed, and 315 received high-dose chemotherapy (HDC) followed by
      PBSC support. The median numbers of CD34+ cells collected in a median of two
      apheresis following ID-Cy and HD-Cy were 19.9 and 22.2 x 10(6)/kg, respectively
      (p = 0.04). The fractions of patients achieving CD34+ cell doses > or = 2.5 or >
      or = 5.0 x 10(6)/kg were not different between the two regimens. More patients
      receiving HD-Cy had grade 3-4 nausea (p = 0.001), vomiting (p = 0.03), and
      mucositis (p = 0.04). The fractions of patients having a neutrophil nadir < 0.5 x
      10(9)/L following ID-Cy and HD-Cy were 0.83 and 0.95, respectively (p = < 0.001).
      The fractions of patients having a platelet nadir < 25 x 10(9)/L following ID-Cy
      and HD-Cy were 0.13 and 0.51, respectively (p = < 0.001). More patients in the HD
      Cy group received platelet (p < 0.001) and red blood cell (p < 0.001)
      transfusions and were admitted to the hospital more frequently (p = 0.03) than
      patients receiving ID-Cy. Three hundred fifteen patients received HDC followed by
      infusion of PBSC. There were no significant differences in the incidence of
      transplant-related death or early survival between patients receiving ID-Cy or HD
      Cy followed by HDC. It was concluded that a regimen of Cy 2 g/m2 with etoposide
      and G-CSF was effective for mobilization of PBSC with low morbidity and resource
      utilization in patients with limited prior chemotherapy exposure.

PMID- 9597572
TI  - CD34 augmentation improves allogeneic T cell-depleted bone marrow engraftment.
AB  - T cell depletion (TCD) performed by elutriation has decreased the incidence of
      acute and chronic graft-versus-host disease (GvHD) following bone marrow
      transplantation (BMT). However, as with all forms of TCD, patients may experience
      graft failure (10%), delayed engraftment, and mixed chimerism. Because 66%-75% of
      the CD34+ cells coseparate with the small lymphocytes, which are removed by
      elutriation, we designed a phase I trial in HLA-identical siblings to determine
      if the readdition of these previously lost small CD34+ cells would improve
      elutriation's engraftment kinetics. CD34+ cells were isolated from the small cell
      fraction of 10 consecutive donor grafts and infused into the recipients along
      with the TCD graft. The positively selected product had a mean T cell content of
      1.2 x 10(5)/kg and was 80% CD34+, doubling the CD34+ content of the graft. All
      patients engrafted promptly with a median time to 500 neutrophils/mm3,
      untransfused 50,000 platelets/mm3, and discharge from the hospital of 19 (range
      10-25), 24 (14-52), and 24 (18-29) days, respectively. Acute GvHD occurred in 2
      patients, and no patient had chronic GvHD. Augmenting stem cell dose may be an
      efficient and safe alternative for overcoming TCD-associated delayed engraftment
      and graft failure, rather than increasing immunosuppression.

PMID- 9597573
TI  - CD19 selection improves the sensitivity of B cell lymphoma detection.
AB  - Reinfusion of residual tumor cells into B cell non-Hodgkin's lymphoma (B-NHL)
      patients during autologous transplantation may be an important cause of disease
      relapse. Determining the extent to which B-NHL cells are present in autologous
      progenitor cell products and if the presence of residual B-NHL cells is
      predictive of relapse will require extremely sensitive methods of detecting rare
      B-NHL cells. We attempted to improve the sensitivity of polymerase chain reaction
      (PCR)-based detection of rare B-NHL cells by preselecting CD19+ cells using an
      immunomagnetic column. To measure detection sensitivity, we prepared samples
      containing different levels of B-NHL cell contamination by mixing B-NHL cell
      lines containing the chromosomal translocation t(14;18) bcl-2/JH) with control
      leukapheresis samples. DNA extracted from each CD19-selected sample and from each
      matched nonselected sample was added to a PCR to amplify the bcl-2/JH breakdown
      junction. CD19 preselection improved the sensitivity of detection of t(14;18)
      positive B-NHL cells 115-fold, so that B-NHL cells at a concentration of 1 tumor
      cell per 1 x 10(6) hematopoietic cells were detected in every specimen evaluated.
      t(14;18)-positive cells were not detected in any of 13 control leukapheresis
      specimens. We conclude that a combination of CD19 preselection and PCR
      amplification may improve the sensitivity of detection of rare lymphoma cells by
      two orders of magnitude without a significant decrease in specificity.

PMID- 9597574
TI  - Sequential CD34+ and CD4+ cell selection from leukapheresis components.
AB  - We tested the feasibility of sequential selection of CD34+ and CD4+ cell-enriched
      fractions from aliquots of five autologous leukapheresis components. CD34+ cells
      were selected from a median 8.0 x 10(8) mononuclear cells using the CellPro
      CEPRATE LC cell separation system. All cells in the CD34-depleted fraction
      (median 4.8 x 10(8), range 0.6-10.0 x 10(8) were then incubated with the
      appropriate antibodies for CD4+ cell selection and passed through a second LC
      column. Median target cell purities of the CD34+ cell-enriched fraction and CD4+
      cell-enriched fraction were 90.5% and 86.0%, respectively. This study
      demonstrates that high purity CD34+ and CD4+ cell-enriched fractions can be
      isolated sequentially from leukapheresis components. In addition, CD8+
      lymphocytes, implicated in graft-versus-host disease, were depleted in the course
      of both positive selection procedures. This approach could decrease the number of
      donor procedures by providing separate CD34(+)-enriched and CD4(+)-enriched
      populations for allogeneic peripheral blood progenitor cell transplantation and
      subsequent donor lymphocyte infusion from the same leukapheresis component.

PMID- 9597575
TI  - CD34+ cell engraftment, ex vivo expansion, and malignant cell depletion following
      immunomagnetic selection.
AB  - This review describes the published preclinical and clinical data on the use of a
      manual or semiautomated immunomagnetic selection device, termed the Isolex
      system. Preclinical evaluation of hematopoietic progenitor cells (CD34+ cells)
      selected from bone marrow, peripheral blood leukapheresis products, and umbilical
      cord blood is reviewed with respect to differentiation (CFU-GM, BFU-E, and CFU
      GEMM formation) and proliferation. The purities and yields of CD34+ cell products
      from clinical trials performed since 1994 are presented along with data on
      malignant cell depletion. On average, the Isolex system resulted in a final
      product median purity of 67% and a final product median yield of 64%. Positive
      selection of CD34+ cells with this device decreased residual tumor cell levels by
      2-3 logs in autologous transplant products and reduced T cell levels by 3-4 logs
      in allogeneic grafts. To evaluate the clinical effect of these immunomagnetically
      selected cells, data on the rate of engraftment were reviewed. Autologous CD34+
      cell transplantation resulted in recovery time from neutropenia (ANC >
      500/microliter) of 9-14 days and recovery time from thrombocytopenia (platelet
      count > 20,000/microliter) of 10-20 days. These data showed that the Isolex
      system can positively select progenitor cells to reconstitute the hematopoietic
      system following myeloablative therapy.

PMID- 9597576
TI  - Long-term cryopreservation: successful trilineage engraftment after autologous
      bone marrow transplantation with bone marrow cryopreserved for seven years.
AB  - Successful autologous bone marrow transplantation (ABMT) and peripheral blood
      stem cell transplantation depend on safe hematopoietic stem cell (HSC)
      cryopreservation and storage. Several successful methods for cryopreservation and
      storage have been established and are commonly used all over the world. However,
      little is known about the effects of long-term cryopreservation on the capacity
      to sustain a complete immunohematopoietic engraftment. Several authors have
      investigated stem cell viability after cryopreservation and storage for more than
      5 years and reported preclinical good viabilities in terms of dye-exclusion or
      colony-forming capability in vitro. Only two studies using BM cryopreserved for
      more than 5 years for transplantation are reported, but they did not provide
      proof of trilineage engraftment. In February 1997 at our institution, a patient
      with relapsed non-Hodgkin's lymphoma underwent ABMT with BM harvested in February
      1990. He achieved a granulocyte count > 500 x 10(6)/L on day 21 and a self
      supporting platelet count > 20 x 10(9)/L on day 30. After day 29, his hemoglobin
      level was satisfactory without need of transfusion support. This successful
      trilineage engraftment with cryopreserved BM that had been stored for 7 years
      suggests that HSC are able to maintain their capability to reconstitute
      hematopoiesis for a long time.

PMID- 9597578
TI  - Model-based estimation of cardiovascular repolarization features: ischaemia
      detection and PTCA monitoring.
AB  - The ST-T segment of the surface ECG reflects cardiac repolarization, and is quite
      sensitive to a number of pathological conditions, particularly ischaemia. ST-T
      changes generally affect the entire waveshape, and are inadequately characterized
      by single features such as depression of the ST segment at one particular point.
      Metrics which represent overall waveshape should provide more sensitive
      indicators of ST-T wave abnormalities, particularly when they are subtle,
      intermittent or periodic. This study discusses a Karhunen-Loeve transform (KLT)
      technique for the analysis of the ST-T waveform. The KL technique was used to
      analyse the ST-T complexes in the ESC ST-T database. KL coefficients were plotted
      as a function of time, and were effective in detection of transient ischaemic
      episodes. Twenty per cent of the records showed bursts of periodic ischaemia
      suggesting local vascular instability. A comparison between kl and ST depression
      series has shown the KL technique as more appropriate to the study of ST-T
      complex variations. Using the kl series, an ischaemia detector has been developed
      based on a resampled, filtered, and differentiated KL series. This technique
      demonstrates a sensitivity of 65% and a specificity of 54%. These low values can
      be due to shifts of the electrical axis which are detected as ischaemic changes,
      real ischaemic episodes that were not annotated with the protocol used at the
      European ST-T database, or erroneous detections. An increase in sensitivity can
      be obtained at the expense of a decrease in the positive predictive value and
      thus becomes a useful technique for previous scanning of the ECG record and
      subsequent review by the expert. The technique has also been used to monitor
      patients during a PTCA process, demonstrating that this technique allows us to
      monitor PTCA-induced ischaemia. A detailed analysis has shown that in some cases
      a repetitive oscillatory behaviour appears, lasting for a period of around 20 s,
      and highly related to the oscillatory behaviour of the HR. In other cases,
      transient changes in KL series with salves behaviour associated with the
      injection of contrast are shown on the ST-T waveform. We conclude that the KL
      based analysis of the ST-T segment is a robust and sensitive technique, with
      considerable advantages over single feature measures in characterizing the subtle
      waveform changes which may be of importance in clinical risk detection.

PMID- 9597577
TI  - Comparison of CapiFlow and frame by frame analysis for the assessment of
      capillary red blood cell velocity.
AB  - CapiFlow (CF), a new fully computerized system for the measurement of capillary
      blood velocity (CBV) was compared to manual frame by frame analysis (a) in a
      model system, and (b) in finger nailfold capillaries recorded on video tape. In
      the model the overall agreement between the two methods was very good (figure 1),
      with no significant differences being noted between the two sets of results and
      the calculated velocities. However, when comparing frame by frame and CapiFlow
      directly, CapiFlow read on average 4.50 +/- 5.21% higher than frame by frame
      analysis (figure 2). The in vivo results obtained by the two methods showed
      similar dynamic changes although some differences between the overall mean CBVs
      were noted (capillary 1, manual 0.13 +/- 0.59 mm s-1 versus CF 0.12 +/- 0.02 mm s
      1, (mean +/- SD), p = 0.354; capillary 2, manual 0.66 +/- 0.23 mm s-1 versus CF
      0.47 +/- 0.09 mm s-1, p < 0.001; capillary 3, manual 2.53 +/- 0.73 mm s-1 versus
      CF 2.35 +/- 0.34 mm s-1, p = 0.062). Further analyses established the optimum
      settings of delta limit and cross correlation. Investigations into the effects of
      changes in window size, window distance or video settings on CBV results obtained
      by CapiFlow, indicated that only settings radically different from the optimum
      had a significant effect on the results obtained.

PMID- 9597579
TI  - Results of the performance testing of purpose-built and PC-based
      electrocardiographs using a simple evaluation procedure.
AB  - This paper presents the results of the evaluation testing of six 12-lead
      electrocardiographs, three purpose-built instruments and three of the recently
      introduced personal computer-based type (PC-based). As for PC-based
      electrocardiographs, three examples of the MRT systems, two examples of the 300
      Hz CardioScope model and one prototype of the 1200 Hz CardioScope were examined
      but only results for one representative example of each are given here. It was of
      particular interest to compare the performance advantages and limitations of the
      PC-based electrocardiographs with that of instruments currently in use. A test
      procedure was developed that can be used by a medical technical department to
      evaluate an electrocardiograph before making a purchase decision. The procedure
      includes tests of frequency response, sampling rate, 50 Hz filter attenuation,
      gain and common mode rejection ratio (CMRR) plus tests based upon simulated
      electrocardiograms (ECGs). The procedure takes account of the AHA and ECRI
      recommendations for electrocardiograph checks and can be completed in less than
      two hours. The only equipment required being an ECG simulator and a signal
      generator. The results of this work show that purpose-built electrocardiographs
      meet all normal performance requirements, whereas the PC-based types, whilst
      having the potential to at least equal these requirements, currently exhibit
      software and hardware related problems.

PMID- 9597580
TI  - Heart response to horizontal impulse.
AB  - Lumped body parameters linear and nonlinear models have been developed and used
      for the analysis of the response of the heart in a seated human body due to
      impulsive horizontal inputs at various body segments. The acceleration transfer
      magnitude and phase due to impulsive inputs at various body segments are
      reported. Time histories of the heart acceleration transfer were obtained for
      both linear and nonlinear models. The results indicate that the largest
      acceleration transfer occurs at 2-3 Hz frequency. Inputs at the upper body
      segments excite a second peak and in the acceleration transfer at 10-12 Hz. The
      nonlinear model shows large attenuation at the high frequency range (larger than
      10 Hz) and less attenuation at the 1-5 Hz frequency range.

PMID- 9597581
TI  - Long-term ambulatory monitoring of urine leakage in the elderly: an evaluation of
      the validity and clinical applicability of thermistor signalling.
AB  - This study evaluated the validity and applicability of a low-cost Urine Leakage
      Recording Device (ULRD) in a geriatric setting. The ULRD consisted of a
      thermistor, connected to a portable, digital datalogger. The thermistor was
      positioned on a commercially available adult diaper. Five healthy females were
      instructed to void urine in seven behavioural conditions comprising general motor
      activity patterns of the average, psychogeriatric elderly in-patient. Voids were
      verbally indicated by the subjects and concomitantly recorded by the ULRD and the
      observer. After comparing the ULRD records--scored by three independent assessors
      -with the subjects' reports, on average (SD) 5.3 (0.6) of a total of 10 voids
      were classified correctly, whereas 9.3 (1.3) false positive events were
      indicated. None of the subjects reported any inconvenience as a result of the
      recording procedure. Although the ULRD is easily applicable, we conclude that it
      seems to be of little value in its present form as a method for long-term
      ambulatory monitoring of urine leakage.

PMID- 9597582
TI  - Comparative analysis of below-knee prosthetic socket liner materials.
AB  - Four materials used in lining prosthetic sockets were compared for their
      potential usefulness in below-knee applications. Tests carried out included
      determinations of resistance to compression, resistance to flexural abrasion and
      coefficients (static and dynamic) of friction. These tests were designed,
      respectively, to assess changes occurring during end-use brought about by
      extensive application of compressive or shear force, and to predict the ability
      to retain contact with the body and socket. Of the four materials in the study
      (Bock-Lite, Pedilin, polyurethane and silicone), Bock-Lite and silicone had high
      compression resistance, Bock-Lite had good resistance to flexural abrasion, and
      polyurethane and silicone had high coefficients of frictional resistance. Thus,
      Bock-Lite will be the most durable of the four materials but, since it had the
      lowest frictional coefficient, it may slip in use. Conversely, silicone and
      polyurethane, which will be retained in position more easily, are easily torn or
      compressed, so are likely to need replacement more frequently.

PMID- 9597583
TI  - A modified Harrington technique for scoliosis.
AB  - Post-Harrington techniques for adolescent idiopathic scoliosis have increased the
      complexity of scoliosis surgery while contributing only biomechanically more
      secure fixation and sagittal contour preservation. On the the basis of principles
      defined by Harrington, the authors developed a simplified technique that
      accomplishes equivalent outcomes.

PMID- 9597584
TI  - Distraction instrumentation outcomes in scoliosis.
AB  - The short-term outcomes of a new distraction technique using a small rod spinal
      instrumentation system (WRIGHTLOCK) are reported for adolescent idiopathic
      scoliosis. No caudally directed thoracic hooks were used. Seventy-four children
      aged 11.7 to 17.5 years who underwent consecutive posterior instrumentations are
      reviewed. Their curves improved from a mean of 55.6 degrees to 22.7 degrees
      (average of 59.2% correction). At 2.7 years mean follow-up, coronal curves lost
      an average of 4.2 degrees correction. Overall, there was a mean increase of 4.4
      degrees in kyphosis. Children with the most preoperative hypokyphosis were
      afforded the greatest gains in kyphosis. Instrumentation resulted in a mean loss
      of 8.2 degrees lumbar lordosis. These results compare favorably with published
      results for other multihook systems.

PMID- 9597585
TI  - Surgical corrections in scoliosis: a meta-analysis.
AB  - A meta-analysis of the acute correction outcomes in adolescent idiopathic
      scoliosis is reported. Posterior instrumentation systems generally gave similar
      coronal plane corrections with average corrections for differing systems ranging
      from 48% to 67%. There was significant overlap of corrections reported for each
      of the systems. Anterior instrumentation gave better results with average
      corrections ranging from 71% to 93%. No instrumentation demonstrated a consistent
      ability to restore a normal thoracic kyphosis, but all seemed to maintain
      preoperative kyphosis measures. All systems, including newer multihook systems,
      showed a small loss of lumbar lordosis postoperatively. The available data
      demonstrates that no posterior implant produces vertebral derotation.

PMID- 9597586
TI  - Effect of wide posterior release on correction in adolescent idiopathic
      scoliosis.
AB  - Wide lumbar posterior release, consisting of partial excision of spinous process,
      excision of interspinous ligament and ligamentum flavum, and excision of facet in
      plane of facet from both outside and within the spinal canal has been employed to
      increase coronal correction and improve the production of lumbar lordosis (10).
      Adolescent idiopathic patients with fusion into the lumbar spine were studied.
      Pre- and postsurgical coronal and sagittal Cobb measurements as well bending
      measurements were done. Intraoperative biplanar radiographs were done after
      positioning, after lumbar rod placement, and finally after wide release and
      placement of the same rod. Statistical analysis was by paired Student's t-test.
      Significantly (p < 0.005), improved correction was attained in the coronal plane
      with release (76% vs. 64%). Total lordosis and instrumented segment lordosis was
      also significantly (p < 0.025) improved with release (12 degrees vs. 3 degrees).
      Coronal and sagittal plane correction in the lumbar spine is improved
      significantly with a wide posterior lumbar release.

PMID- 9597587
TI  - Solid rod short segment anterior fusion in thoracolumbar scoliosis.
AB  - Seventeen patients with adolescent idiopathic thoracolumbar scoliosis underwent
      short segment anterior spinal fusion with a solid rod-screw construct. Patients
      were evaluated radiographically and interviewed using the Scoliosis Research
      Society instrument. Mean radiographic follow-up was 34 months, and mean follow-up
      at time of interview was 62 months. Mean curve correction was 87%, declining to
      67% at 2 years. Mean correction of the instrumented curve was 114%, declining to
      103% at 2 years. The thoracic curve improved 24% and remained stable throughout
      the follow-up period. Kyphosis over the instrumented segments increased from 4
      degrees preoperatively to 10 degrees postoperatively. Although there was a trend
      toward increasing kyphosis over time, this was not statistically significant at
      final follow-up. Most patients (88%) were extremely satisfied with the surgical
      result. We believe that a short-segment anterior fusion with a solid rod-screw
      construct provides excellent curve correction with minimal kyphosis over the
      instrumented segment. Overcorrection of the instrumented segment must be achieved
      for this technique to be successful.

PMID- 9597588
TI  - Clotting parameters in patients with adolescent idiopathic scoliosis undergoing
      posterior spinal fusion and instrumentation.
AB  - Thirty-six patients, 9 males and 27 females, average age 13.2 years, undergoing
      posterior fusion and segmental instrumentation surgery for idiopathic adolescent
      scoliosis were studied for abnormalities of platelet count (PC), prothrombin time
      (PT) and partial thromboplastin time (PTT). Intraoperative and immediate
      postoperative values were obtained at 2, 4, 6, 12, 24, and 48 hours. All patients
      showed diminution of platelet counts during the study period, but mean values
      were reduced below normals only at 4 hours after operation. The PT was
      significantly elevated in all patients intraoperatively and for the first 24
      hours postoperatively, with return to normal by 48 hours. The PTT levels were
      essentially unaffected at any time.

PMID- 9597589
TI  - Selective treatment program for developmental dysplasia of the hip in an
      epidemiologic prospective study.
AB  - Over 1 year of ultrasound (US) mass screening, 4,568 newborns were examined
      consecutively at age 3-4 weeks using both clinical and ultrasonographic
      examination methods. The US examination involved both the static and dynamic
      scanning. In total, 25 babies were treated early (5.5 per 1,000), and 6 babies
      were given late treatment for postnatally developing acetabular dysplasia (1.3
      per 1,000). Early treatment was instituted only for hips remarkably distorted
      anatomically, as could be seen from their shape on the static scan, and for those
      that were sonographically unstable with an apparent stress displacement. Clinical
      examination at age 3-4 weeks failed in more than half of all sonographically
      abnormal cases. In one case, the postnatal development of the hip joint was
      associated with the worsening of its formation and a developing subluxation
      despite its primary normal characteristics.

PMID- 9597590
TI  - Triggering in the mucopolysaccharidoses.
AB  - Upper limb dysfunction, particularly in relation to skeletal dysplasia and median
      nerve dysfunction, is well recognized in the mucopolysaccharidoses and
      mucolipidoses. This is of increasing importance because bone marrow
      transplantation has dramatically improved survival without changing the
      musculoskeletal manifestations. Triggering at the A1 pulley and more distally has
      been described in these patients. We report two such cases and four other
      patients who were noted to have triggering at the carpal tunnel in association
      with carpal tunnel syndrome. Five of the six patients consented to surgical
      intervention with favorable outcomes.

PMID- 9597591
TI  - The role of magnetic resonance imaging in the investigation of spinal dysraphism
      in the child with lower limb abnormality.
AB  - A review of magnetic resonance imaging (MRI) performed to exclude the presence of
      spinal dysraphism in children presenting with lower limb pathology is unrewarding
      in the absence of abnormal neurology. Over a 5-year period, 29 children ages 2
      weeks to 15 years with a mean age of 6 years presenting with lower limb
      abnormalities were referred for MRI of the spine to exclude an occult neurologic
      cause for the deformities. More than one limb abnormality, for example pes cavus
      and limb length discrepancy, was present in 93% of the children, and 11 children
      had severe or recurrent talipes equinovarus deformity. Only two children (7%),
      both of whom had abnormal limb neurology, had abnormal MRI scans. In the absence
      of a demonstrable neurologic deficit in the lower limb, there appears to be no
      advantage in requesting MRI of the spine in children presenting with lower limb
      abnormality.

PMID- 9597592
TI  - Sonographic monitoring of the treatment of developmental disturbances of the hip
      by the Pavlik harness.
AB  - This study was undertaken to verify the efficacy of the Pavlik harness in the
      treatment of developmental disturbances of the hip (DDH) when reduction and
      stabilization of the hip and conclusion of the treatment are monitored by
      sonography. With active mother participation, under direct supervision of one
      consistent orthopaedist, 547 patients (60 with 91 unstable hips; 196 with 232
      dysplastic hips, types IIb, IIc, and D; and 291 with 376 dislocated hips types
      IIIa, IIIb, and IV), with an average age of 2.3 months were evaluated. The
      initial hip flexion in the harness was 60 degrees to 70 degrees, which was
      adjusted frequently until concentric hip reduction. Sonographic reduction was
      achieved in 89.7% of the hips in 2 weeks, in 8.3% in 3 weeks, and in 2% in 4
      weeks. Sonographic hip stabilization was achieved in 87.4% in 4 weeks, in 9.8% in
      5 weeks, and in 2.9% in 6 weeks. Soft tissue landmarks (the cartilaginous roof
      angle and capsule) were used for assessment of reduction and stabilization, but
      for conclusion of the treatment, bony roof angle was used as well. Fulltime
      harness treatment averaged 2.7 months for the whole group (1.4 months for
      unstable hips, 2.3 months for dysplastic hips, and 3 months for dislocated hips).
      The harness was abandoned in five patients, four because of mother noncompliance
      and one because of abdominal surgery. Other serious complications, including
      avascular necrosis (AVN), did not occur in this study. It was concluded that
      paying attention to the minute details of treatment with active engagement of the
      mother in the form of group therapy under direct and consistent supervision of
      one orthopaedist coupled with sonographic monitoring can ensure satisfactory
      outcome with a shorter period of treatment in a very high percentage of the
      cases.

PMID- 9597593
TI  - Salter's innominate osteotomy: the biologic stimulating effect.
AB  - This study entails the follow-up of 28 patients (33 hips) with congenital hip
      dislocation. The primary treatment was one-stage open reduction and Salter type
      osteotomy. The mean follow-up period was 5 years and 6 months (range = 3 years to
      7 years 4 months). At last follow-up, 9 hips (27%) were classified as excellent,
      22 hips (67%) as good, and 2 hips (6%) as fair. Avascular necrosis developed in
      two hips (6%) postoperatively. The difference between the acetabular index at
      immediate postoperative time and at last follow-up was statistically significant
      (p < 0.01). The Salter osteotomy by itself may have a biologic stimulating effect
      on the acetabulum, which accentuates reversal of the dysplastic changes.

PMID- 9597594
TI  - Bone growth after lengthening of the lower limb in children.
AB  - Femoral and tibial growth was studied in 6 children undergoing a femoral
      lengthening and 28 children a tibial lengthening. Growth of both femurs and
      tibiae was evaluated for 3 years both before and after the procedure. No
      significant growth disturbance was noted in femoral lengthenings of 14%. However,
      growth variations were constant after tibial lengthening of 18% on the average
      and could be correlated to the amount of lengthening. The consequences of these
      changes are limited in terms of final limb length because overgrowth of the femur
      often compensates for growth retardation of the tibia when tibial lengthening is
      less than 18%. Experimental and clinical studies assert that lengthenings of more
      than 30% can result in significant and definite growth retardation of the
      lengthened bone.

PMID- 9597595
TI  - Characteristics of patients with symbrachydactyly.
AB  - The clinical and radiologic spectrum of symbrachydactyly has been extended, on
      the basis of experimental embryology, into four categories: typical
      symbrachydactyly, atypical cleft hand, monodactyly, and adactyly. The origin of
      this embryologic failure is probably a vascular disruption. A series of 64 hands
      and 3 feet are reported, indicating associated anomalies and possible etiologic
      features.

PMID- 9597596
TI  - Modified step-cut osteotomy of the humerus.
AB  - Corrective osteotomy of the distal humerus for a posttraumatic cubitus varus was
      performed in 31 patients using a modified step-cut osteotomy. The average patient
      age was 14.3 years. Complete bony union was obtained between the 8th and 16th
      weeks. Twenty-one patients achieved excellent results, 7 achieved good results,
      and 3 achieved poor results on the basis of Oppenheim's criteria. Although the
      results for 28 patients (90.3%) were classified as excellent or good, 6 patients
      (19.3%) were subjectively disappointed due to bulging of the lateral condyle. We
      achieved an overall improvement in mechanical stability and established an easier
      technique in corrective osteotomy. However, this approach may not be appropriate
      if the correction angle desired is greater than 30 degrees.

PMID- 9597597
TI  - Reimplantation of growth plate chondrocyte cultures in central growth plate
      defects: Part I. Characterization of cultures.
AB  - Growth plate lesions or resections may cause severe growth arrest because of the
      bony bridge between the epiphysis and metaphysis. Actual treatments for
      epiphysiodesis include resecting the bone bar and setting an interpositional
      material. Growth plate cultures may provide the appropriate cartilage necessary
      to restore growth potential when implanted in a growth plate defect. The aim of
      this work was to determine certain cell culture parameters in order to optimize
      in vitro cultures to obtain abundantly mature and functional chondrocytes. We
      studied the manner in which enzymatic digestion, carried out by various enzymes,
      obtained chondrocytes. Treatment with trypsin (0.2%) during 30 minutes at 37
      degrees C and then collagenase (200 U/mL) during 6 hours was chosen. Under these
      conditions, 40 +/- 16 10(6) chondrocytes per gram of growth plate were obtained,
      and cellular viability was 79 +/- 12%. The density of the cellular seeding, the
      nature of the culture substrate, and the culture medium composition were
      determined to optimize the growth of differentiated cells. Seeding at 20,000 or
      30,000/cm2 on a type I substrate and Ham F-12 medium not supplemented with either
      glucose or growth factors was demonstrated to be the best choice for this
      purpose.

PMID- 9597598
TI  - Reimplantation of growth plate chondrocyte cultures in central growth plate
      defects: Part II. Surgical experimentation in rabbits.
AB  - An original and reliable technique to culture growth plate chondrocytes was
      developed to obtain an abundant amount of mature and functional chondrocytes.
      Growth plates were provided from the epiphysis of 3-week-old rabbits. Isolation
      of the chondrocytes was optimized by the use of trypsin and collagenase. The
      culture was realized according to the following conditions: seeding at 20,000 or
      30,000/cm2 on type I collagen substrate and in Ham F-12 medium without a
      supplementation of glucose or growth factors. After 7 days of culture, the
      implantation was to be carried out. Different implantation substrates were
      evaluated in vivo. Agar turned out to be the only substrate to provide strong and
      healthy chondrocytes 21 days after the grafting. Then implantation was tested on
      large iliac resections in rabbits to check whether an enchondral ossification
      occurred with the culture. Poor results were obtained because of an early
      disappearance of the cultured chondrocytes. In an other experimentation, the
      culture was implanted into surgically created defects in the growth plate area.
      In this case, the culture did produce an epiphysiodesis. However, the 6-week
      postoperative histological examination showed that the implant remained viable,
      continued to maintain a proteoglycanrich matrix, and began to organize in ordered
      columns of mature chondrocytes.

PMID- 9597599
TI  - Tooth structure loss apical to preparations for fixed partial dentures when using
      self-limiting burs.
AB  - STATEMENT OF PROBLEM: Burs with guide pins may be used to limit the depth of
      tooth preparation for fixed partial dentures. The effects of guide pins on tooth
      structure apical to the finish line after tooth preparation for fixed partial
      dentures has not been recorded. PURPOSE: This in vitro study recorded loss of
      tooth structure within 1.0 mm apical to the finish line of teeth prepared with
      straight cylinder and tapered cylinder self-limiting burs and one conventional
      bur. MATERIAL AND METHODS: Forty-five extracted human teeth were randomly divided
      into three groups. The facial surface of each tooth was prepared with two types
      of diamond burs with guide pins and a conventional diamond for the control. The
      surface was profiled before and after tooth preparation. Profiled surfaces were
      analyzed and the groups were compared using analysis of variance and the Tukey
      Kramer HSD test (alpha = 0.05). RESULTS: No significant difference was recorded
      between the control group and the group prepared with a round-ended tapered
      cylinder self-limiting pin. However, there was a statistically significant
      difference between the control and cylindrical pin groups, and between the two
      groups prepared with self-limiting diamonds. CONCLUSION: This study revealed
      abrasion apical to the finish line of the preparation in all groups. The
      cylindrical guide pin group exhibited the greatest loss of tooth surface.

PMID- 9597600
TI  - Effect of mixing technique on surface characteristics of impression materials.
AB  - STATEMENT OF PROBLEM: Previous studies have shown a relationship between the
      disinfection process, wettability, and mass change of impression materials. Hand
      mixed high viscosity impression materials usually result in a material with
      numerous voids, which contribute to surface roughness and affect the surface
      characteristics of the material. PURPOSE: This study evaluated the effect of
      mixing technique on advancing contact angle, receding contact angle, imbibition,
      and mass loss of various high and low viscosity polyether and polyvinyl siloxane
      materials. The null hypothesis tested was no differences exist between the
      different mixing systems. MATERIAL AND METHODS: The Wilhelmy technique was used
      for deriving wetting properties of the materials used (Impregum F and Penta,
      Permadyne Syringe, Garant and Penta, Dimension Penta and Garant L, Aquasil).
      Conditions included no disinfection (0 hours) and 1, 5, and 18 hours of immersion
      disinfection in a full-strength solution of 2% acid glutaraldehyde disinfectant
      (Banicide). Weight changes before and after disinfection were measured to detect
      weight loss or mass increase over time. Weight loss in air was also measured to
      detect mass loss. Data were analyzed with a one-way analysis of variance at alpha
      = 0.05. RESULTS: All materials displayed some degree of imbibition of the
      disinfectant and experienced mass loss with polymerization, except the light
      viscosity polyvinyl that gained 0.18% at 5 hours. No significant differences were
      found in wettability among the polyether materials after 1 hour of disinfection.
      Less imbibition was observed for high viscosity mechanically mixed materials
      compared with the hand-mixed materials for both polyether and polyvinyl siloxane
      at 1-hour disinfection time. CONCLUSIONS: Polyether materials were more wettable
      than polyvinyl. Imbibition of high viscosity polyether and polyvinyl materials
      after 1 and 18 hours of disinfection were affected by the mixing system used.

PMID- 9597601
TI  - Tensile bond strengths of dual-cured cements between a glass-ceramic and enamel.
AB  - STATEMENT OF THE PROBLEM: Dual-cured cements have been used with castable ceramic
      restorations, but the tensile bond strengths of these materials have not been
      thoroughly researched. PURPOSE OF THE STUDY: This study compared the tensile bond
      strengths between Dicor castable ceramics and enamel of four dual-cure cements:
      Twinlook, Optec Dual-Cure Luting Cement, Clearfil CR Inlay, and Dual Cement.
      MATERIAL AND METHODS: Truncated cones made of Dicor castable ceramics were
      cemented to enamel of freshly extracted anterior teeth with these four cements.
      Before testing, all specimens were immersed in water at 37 degrees C for 24
      hours, and thermocycled 1000 times in 5 degrees C and 55 degrees C water, with a
      dwell time of 30 seconds each. Tensile force was used to separate each specimen
      with the Instron universal testing machine. RESULTS: Clearfil CR Inlay cement
      exhibited the highest mean tensile bond strength (18.4 MPa), followed by Dual
      (18.3 MPa), Twinlook (15.2 MPa), and Optec Dual-Cure luting (14.9 MPa) cements.
      One-way analysis of variance did not reveal any significant differences (p =
      0.05) among groups. A majority of the fracture was adhesive at the ceramic and
      cement interface. CONCLUSION: All four dual-cured cements formed strong bonds
      between enamel and Dicor cement, ranging from 14.90 MPa to 18.35 MPa, and there
      was no statistically significant difference.

PMID- 9597602
TI  - Effect of ceramic surface treatments on the bond of four resin luting agents to a
      ceramic material.
AB  - PURPOSE: This study evaluated the effect of various ceramic surface treatments on
      the shear bond strengths of four resin luting agents to Cerec 2 ceramic material.
      MATERIAL AND METHODS: Four ceramic surface treatments were performed. All groups
      were subjected to the control treatment, which was abrasion with No. 600 silicon
      carbide paper. The other three group treatments were etching with phosphoric acid
      gel, application of bonding agent containing silane coupler, and application of
      silane coupling agent after etching with phosphoric acid gel. Cerec 2 ceramic
      specimens were treated with one of the four methods and then cemented together
      with each of the four resin luting agents (Super-Bond C&B, Panavia 21, Clapearl,
      and Vita Cerec Duo Cement). Half of the specimens were stored in water and the
      other half were thermal cycled before shear bond strength testing. RESULTS:
      Treatment with the silane coupler improved the shear bond strength compared only
      with the abrasion with carbide paper (control). When the ceramic material was
      treated with the silane coupler or the silane coupling agent after etching with
      phosphoric acid gel, no significant differences in bond strength were noted
      between water storage and 20,000 thermal cycles for any of the four resin luting
      agents. After 20,000 thermal cycles, all specimens treated with the silane
      coupling agent with phosphoric acid gel except those cemented with Super-Bond C&B
      resin luting agent after etching showed cohesive failures within the ceramic.
      CONCLUSION: Combined surface treatment of etching with phosphoric acid and
      application of silane coupling agent provides the highest bond strengths of resin
      luting agents to Cerec 2 ceramic material after thermal cycling.

PMID- 9597603
TI  - Effects of dental laboratory processing variables and in vitro testing medium on
      the porcelain adherence of high-palladium casting alloys.
AB  - PURPOSE: This study assessed the effects of dental laboratory processing
      variables and testing medium on porcelain adherence of representative high
      palladium alloys. MATERIAL AND METHODS: The processing variables were recasting
      two and three times, porcelain stripping with hydrofluoric acid and rebuilding,
      and changing the recommended oxidation procedures. The testing medium was air for
      these four groups and the nontreatment group. In the last group, the specimens
      were stored and tested in artificial saliva. The metal ceramic specimens were
      fractured with biaxial flexure in constant strain. The area fraction of adherent
      porcelain (%) was calculated with a standardized spectrometric technique. A gold
      palladium alloy served as the control. RESULTS: Recasting without adding new
      alloy negatively affected some high-palladium alloys. Porcelain stripping did not
      cause a decrease in adherence of the tested alloys. The alternate oxidation
      treatment reduced significantly the porcelain adherence of the Au-Pd and one Pd
      Cu-Ga alloy. Storage and testing in artificial saliva did not significantly
      affect the porcelain adherence of the alloys. The Au-Pd alloy exhibited the
      highest porcelain adherence.

PMID- 9597604
TI  - Retention of three endodontic posts cemented with five dental cements.
AB  - STATEMENT OF PROBLEM: The retention of a post is believed to be a major factor in
      restoration survival. Therefore the cement with the greatest in vitro retention
      property should give the best performance for a restoration. PURPOSE: This study
      compared retentive values of three posts (Flexi-Post, AccessPost, and ParaPost)
      cemented with five cements (Flexi-Flow, zinc phosphate, Advance, Duet, and Ketac
      Cem) plus a control group that consisted of a Flexi-Post No. 2 dowel without
      cement. MATERIAL AND METHODS: A total of 160 recently extracted human single
      rooted teeth with crowns removed at the cementoenamel junction were divided into
      16 groups of 10 samples. Post holes were prepared according to manufacturers'
      instructions. Posts were then cemented with one of the five cements. Each sample
      was placed into a specialized jig and on a tensile testing machine with crosshead
      speed of 0.638 cm/minute, applied until failure. A two-way analysis of variance
      and Newman-Keuls multiple range comparison tests were performed for all cemented
      groups. A one-way analysis of variance and a Student-Newman-Keuls multiple range
      comparison test were performed only for the groups with the Flexi-Post dowel,
      this included the no cement condition, with significant results if p < 0.05.
      RESULTS: Flexi-Post dowel with Flexi-Flow Natural cement obtained the highest
      retentive value (303.91 pounds). ParaPost dowel with Duet cement exhibited the
      lowest retention value (21.23 pounds). The Flexi-Post dowel demonstrated higher
      mean retention than AccessPost or ParaPost dowels, AccessPost dowel was higher
      than ParaPost dowel. Flexi-Flow cement had the highest overall mean retention
      followed, in decreasing order, by zinc phosphate, Advance, Ketac-Cem, and Duet
      cements. CONCLUSIONS: Flexi-Post dowel was the most retentive post studied with
      values ranging from 303.91 pounds with Flexi-Flow Natural cements to 150.93
      pounds without cement. Flexi-Flow cements had a higher overall mean retention
      than other cements studied.

PMID- 9597605
TI  - Associations between selected demographic parameters and dental status: potential
      implications for orodental rehabilitation.
AB  - PURPOSE: This pilot study evaluated potential relationships between dental status
      and various sociodemographic variables in the age group segment of the United
      States population at greatest risk for the disruption of dental function due to
      treatment of an oral cavity cancer. METHODS: The Dental Health Supplement of the
      1989 National Health Interview Survey was used to evaluate the self-reported
      status of natural dentition and prior dental rehabilitation among the population
      of persons 45 years or older. RESULTS: Sociodemographic variables, which showed a
      significant association with status of natural dentition, were level of income
      and occupation at lower income levels (p < 0.05). Increased levels of prior
      dental rehabilitation were significantly associated with lower age, female
      gender, increased level of income, and occupation (p < 0.05). Occupations that
      required social interaction had the highest levels of both status of natural
      dentition and prior dental rehabilitation (p < 0.05). CONCLUSIONS: Overall dental
      status after treatment of oral cancer may be related to the occupational status
      of many persons. Sociodemographic factors that influence the dental
      rehabilitation needs of individual patients after treatment of an oral cancer
      should be considered in policy decisions affecting accessibility of dental
      rehabilitative care. A follow-up, survey study that would further define the
      identified relationships between a person's demographic status and dental
      rehabilitation needs is recommended.

PMID- 9597606
TI  - Comparison of four techniques for monitoring the setting kinetics of gypsum.
AB  - STATEMENT OF PROBLEM: Setting time of gypsum depends on the method of
      measurement. PURPOSE: In this study, four methods for ascertaining the setting
      time of gypsum were compared. MATERIAL AND METHODS: Gypsum setting was evaluated
      with Gillmore needles, setting expansion, scanning electron microscopy, and x-ray
      diffraction. Both die stone (Vel-Mix) and fast-setting dental stone (Snap-Stone)
      were investigated. By using Gillmore needles, both initial set and final set were
      recorded. Setting expansion was monitored until equilibrium was achieved. For
      scanning electron microscopy, samples of mixed stone were immersed into liquid
      nitrogen to stop the reaction. The water was subsequently removed by freeze
      drying. Samples were then examined in a scanning electron microscope. For x-ray
      diffraction, the percentages of dihydrate and hemihydrate crystals were monitored
      every 1.5 minutes. RESULTS: Setting times for the fast-setting type III stone and
      for the regular-setting type IV stone were approximately 3 and 10 minutes,
      respectively, with the Gillmore needle indentation tests; 10 and 20 minutes with
      scanning electron microscopy; and 20 and 60 minutes with x-ray diffraction.
      CONCLUSION: Scanning electron microscopy, setting expansion, and x-ray
      diffraction indicated changes that occurred at times after a clinically relevant
      set was obtained in the gypsum setting reaction.

PMID- 9597607
TI  - Effect of a prosthetic appliance for treatment of sleep apnea syndrome on
      masticatory and tongue muscle activity.
AB  - STATEMENT OF PROBLEM: The efficiency of an appliance for treatment of sleep apnea
      shows inordinate interindividual difference. The mechanism of its therapeutic
      effects remains unresolved. PURPOSE: This study examined the effect of the device
      on sleep apnea, and masticatory and tongue muscles. MATERIAL AND METHODS: Fifteen
      patients with sleep apnea syndrome were evaluated polysomnographically, with and
      without the appliance. Electromyograms (EMG) of genioglossal, masseter, and
      lateral pterygoid muscles were recorded and EMG amplitudes measured before,
      during, and after the apneas. Apneas were classified into three types:
      obstructive, central, and mixed. RESULTS: During obstructive apneas, muscles
      showed significantly lower EMG amplitudes; whereas during central apneas, no
      decrease in the mean EMG amplitude was observed. EMG amplitudes increased after
      insertion of the device. EMG amplitudes during obstructive apneas were
      significantly increased in the genioglossal (p < 0.03, t test) and lateral
      pterygoid muscles (p < 0.03) by the device. Obstructive and mixed apneas per hour
      were significantly reduced by the appliance; however, in contrast, central apneas
      showed slightly increased. The apnea index decreased significantly (p < 0.002) by
      the device owing to the paucity of central apneas. CONCLUSIONS: The apnea
      appliance activated masticatory and tongue muscles during sleep and prevented the
      upper airway from collapsing. The prosthetic appliance was useful in the
      treatment of sleep apnea syndrome.

PMID- 9597608
TI  - Construction faults, age, gender, and relative medical health: factors associated
      with complaints in complete denture patients.
AB  - STATEMENT OF PROBLEM: Many practitioners will experience a situation, whereby a
      patient with newly fabricated complete dentures continues to experience
      difficulty in adapting to them. This can lead to a protracted period of
      discouraging "adjustment appointments" that may not result in the eventual
      resolution of the problem. Therefore it is often concluded that there is some
      patient factor, either age, gender, medical, or psychologic status that is
      hindering the success of treatment. PURPOSE: This study examined a group of 100
      patients who experienced ongoing difficulties with their new complete dentures,
      to determine possible underlying causes. MATERIAL AND METHODS: A retrospective
      study was conducted with information derived from patient records. All patients
      were treated by the same prosthodontist after having been referred specifically
      for their denture problems. Information regarding patient age, gender, medical
      and psychological histories, and information pertaining to the dentures at the
      time of presentation was derived from patient records. RESULTS: Statistical
      analysis comparing age, gender, and medical and psychologic status with the
      number or type of patient complaint failed to show any significant relationships.
      Significant relationships were observed when denture design faults or the
      condition of a patient's mucosa were compared with patient complaints.
      CONCLUSIONS: This study suggests that in most instances, complete denture
      patients present with complaints only when there is a real design fault or a
      tissue problem.

PMID- 9597609
TI  - A randomized clinical trial comparing the efficacy of mandibular implant
      supported overdentures and conventional dentures in diabetic patients. Part I:
      Methodology and clinical outcomes.
AB  - STATEMENT OF PROBLEM: Scientific evidence is lacking to support the general
      application of implant-supported mandibular overdentures. PURPOSE: This
      randomized clinical trial was undertaken to compare the efficacy of conventional
      mandibular and implant-supported overdentures in diabetic edentulous patients
      with clinically acceptable metabolic control. METHOD: A total of 102 diabetic
      patients, treated with or without insulin, were randomized to receive a new
      maxillary denture and either a conventional or an implant-supported removable
      mandibular overdenture. Treatment was completed for 89 patients, 37 with the
      conventional and 52 with implant-supported dentures. Detailed examinations,
      tests, and questionnaires were given before and at 6- and 24-months after
      treatment completion. Comparisons between the two treatment groups were made for
      treatment failures based on prespecifed criteria and the type and amount of
      maintenance care provided. RESULTS: The insulin and noninsulin treated groups
      were collapsed because of the lack of significant differences at entry. The
      conventional denture and implant-supported overdenture groups were similar in
      terms of general demographics, medical status, quality of their original dentures
      and denture support, several functional measures, and patient satisfaction.
      Treatment was judged to be successful in 56.9% of patients with conventional
      dentures and 72.1% with overdentures. This difference in success rate was not
      statistically significant (p > 0.05). Patients with treatment failures in both
      groups required excessive maintenance care. Those with conventional dentures
      needed frequent denture base adjustments and relines, whereas those with
      overdentures required frequent clip replacements and repairs. Although
      significant improvements were seen with both treatment modalities, a higher
      percentage of patients with implant-supported overdentures than those with
      conventional dentures reported improvements in chewing comfort and moderate-to
      complete overall satisfaction.

PMID- 9597610
TI  - Tomographic stability of condyle fossa relationships in 40 treated
      temporomandibular disorder patients.
AB  - STATEMENT OF PROBLEM: Condylar position and stability after treatment of 40
      temporomandibular disorder patients was studied. PURPOSE: This study determined
      pretreatment position and posttreatment condylar stability. MATERIAL AND METHODS:
      Forty temporomandibular disorder patients with symptoms of muscles of mastication
      pain, temporomandibular joint sounds, attrition, interceptive occlusal contacts,
      and restricted range of motion were used. Axial corrected midcut sagittal
      tomograms were made of the 80 temporomandibular joints before treatment. Tracings
      from the tomograms were used to measure and analyze pretreatment position and
      posttreatment stability. RESULTS: Pretreatment condyle fossa position was not
      concentric in 26 of 80 patients (32.5%). Posttreatment condylar position showed
      no change and was statistically stable. CONCLUSION: In this study of 40
      temporomandibular disorder patients, no statistical change in condylar position
      was detected. Variable condylar positions were found in the 80 pretreatment axial
      corrected midcut sagittal tomograms. All patients were asymptomatic after 1 year.

PMID- 9597611
TI  - Outcome assessment of implant-supported prostheses.
AB  - STATEMENT OF PROBLEM: From the dental professional's standpoint, implant
      rehabilitation offers dramatically improved treatment alternatives to orally
      disabled patients. However, what a patient perceives as important to their
      function and satisfaction with their prostheses may be quite different from what
      the dentist believes are significant health-related improvements. PURPOSE: To
      resolve this problem, a series of investigations were designed to measure
      satisfaction and performance in groups of patients who wore various types of
      prostheses supported by endosseous titanium implants. MATERIAL AND METHODS:
      Methods are described for assessing treatment efficacy and population needs,
      including measures of perceived levels of disability, health-related quality of
      life, and functional capacity. RESULTS: The findings highlight patient factors
      that have not been considered before and appear to contribute to the success of
      prosthetic rehabilitation for the edentulous patient. CONCLUSION: Patient
      centered approaches to the assessment of treatment efficacy are highly relevant
      to today's prosthodontists, whose goals are the improvement of function and
      quality of life for their patients.

PMID- 9597612
TI  - Effect of glass fiber reinforcement on some mechanical properties of
      autopolymerizing polymethyl methacrylate.
AB  - PURPOSE: This study investigated the different effects of quantitative
      percentages of glass fiber intensity on the transverse strength, maximum
      deformation, and the modulus of elasticity of acrylic resin. MATERIALS AND
      METHODS: Fifty-four specimens were formed in a specially designed mold to produce
      identical specimens in accordance with the manufacturer's recommendations. Six
      percentages of glass fiber reinforcement in loose random form were studied. Each
      glass fiber treatment percentage (0%, 1%, 2%, 5%, 10%, 15%) was related to the
      total powder/liquid mass. RESULTS: The results indicated that 1% glass fiber
      treatment enhanced the transverse strength of the tested specimen. Maximum
      deformation at failure in the tested treatment groups was found to be different.
      The interaction of glass fiber concentration on fracture strength and deformation
      was significant (p < 0.0001). CONCLUSION: The 1% glass fiber concentration was
      found to give the best fracture strength and deformation results. Significantly
      higher glass fiber percentages was found to weaken the resin.

PMID- 9597613
TI  - Fluctuations in the number and distribution of prosthodontists: 1987-1995.
AB  - PURPOSE: This article presents a review that used three ADA studies on the
      distribution of dentists to determine whether the number of private practice
      prosthodontists in the mid 1990s has kept pace with the population in the various
      regions and states. RESULTS: Findings indicate that between 1987 and 1991 there
      was a marked national increase in numbers of prosthodontists followed by a marked
      decrease during the first half of the 1990s. There continued to be major
      differences, however, in practitioner-to-population ratios in different
      geographic areas. Since the mid 1980s, there has been a general increase in the
      number of graduates from prosthetic programs, but an increasing percentage of
      these graduates were foreign trained dentists. CONCLUSION: There continues to be
      a need to determine the adequacy of the number and distribution of
      prosthodontists.

PMID- 9597614
TI  - Organizational considerations for an electronic curriculum. Part I: A rational
      nosology for concept management in dentistry.
AB  - STATEMENT OF PROBLEM: With the use of multimedia electronic knowledge as a tool
      in dental education, an overriding concern has centered on how to devise an
      organizational model that will accommodate the vast and diverse arrays of
      information involved, yet be sufficiently simple enough to provide students with
      a rational and consistent means of accessing the information they require. By
      adopting the natural history of the diseases dentists are called on to address as
      a common organizing principle, it becomes possible to link all concepts that
      relate to individual problem areas through a technique of retro-mapping. PURPOSE:
      The purpose of this article is to introduce learners to a cognitive "scaffolding"
      that will assist them in achieving a deeper cognitive dimension for problem
      solving.

PMID- 9597615
TI  - A comparison of senior dental students and normative standards with regard to
      caries assessment and treatment decisions to restore occlusal surfaces of
      permanent teeth.
AB  - STATEMENT OF PROBLEM: Even though assessments of borderline restorative items in
      terms of accuracy and interexaminer variation have been reported, no attempt has
      been made to simultaneously evaluate diagnostic and treatment planning decision
      using objective normative standards. PURPOSE: This study established the accuracy
      of caries presence assessment as compared with gold standards, interexaminer
      agreement in assessment of caries presence and restorative needs, and influences
      of perceived caries status and restoration quality on treatment planning in
      borderline restorative situations. MATERIALS AND METHODS: Fifteen senior dental
      students in Mexico City (66% women; mean age 23.2 years) evaluated predetermined
      areas in 109 restored and unrestored posterior teeth in an in vitro model. Teeth
      were subsequently assessed for restoration quality and the presence of enamel and
      dentinal caries by use of histologic and specific dye techniques. Student's t
      test, Cohen's kappa, and Pearson's correlation analyses were used to analyze the
      data. RESULTS: There were significant caries misdiagnoses and substantial
      overtreatment proposed. In a few instances, teeth were left untreated, but
      usually they were programmed for restoration. Interexaminer agreement varied
      markedly and was not high. However, performance while correctly detecting lesions
      was better than in treatment planning. CONCLUSION: There was a high correlation
      between a diagnosis of caries and restorative treatment in unrestored teeth; the
      correlation was lower for restored teeth, although they were allocated to
      restorative treatment more often. This difference hinged on perceived quality of
      the restoration, an important factor in the frequency of proposed re-restoration.

PMID- 9597616
TI  - A procedure for relining a complete or removable partial denture without the use
      of wax.
AB  - Various procedures are used to reline removable dentures. Some of these involve
      the use of wax to seal the denture to the cast for flasking and processing. This
      necessitates the use of high temperatures for an extended period and involves the
      risk of warpage of the denture. It is also relatively time-consuming. This
      article describes a procedure that uses polyvinyl siloxane instead of wax. The
      procedure is more time efficient and decreases the risk of warpage of the
      denture.

PMID- 9597617
TI  - Functional metallic handles for final impressions of complete dentures.

PMID- 9597618
TI  - The future of general medicine.

PMID- 9597619
TI  - Multiple endocrine neoplasia.

PMID- 9597620
TI  - The fat controller: obesity and leptin.

PMID- 9597621
TI  - Endocrine hypertension.

PMID- 9597622
TI  - Diabetes insipidus.

PMID- 9597623
TI  - Polycystic ovary syndrome.

PMID- 9597624
TI  - New treatments for acromegaly.

PMID- 9597625
TI  - Ethics, ideology and rationing in the NHS.

PMID- 9597626
TI  - Two ECGs and a history: a guide to early hospital discharge of patients with
      'chest pain? cause'.
AB  - OBJECTIVES: To shorten the stay in hospital of patients admitted with chest pain
      of uncertain origin, using clinical history and an unchanging ECG as a basis to
      inform patients on the post-take ward round of imminent discharge that same day
      (pending normal cardiac enzyme results), thereby facilitating actual discharge on
      the same day. DESIGN: A prospective observational study over a two-month period
      of consecutive patients admitted with chest pain of uncertain origin. SETTING:
      District general hospital in North-West England with a regional cardiothoracic
      centre on site. RESULTS: Of the 115 patients enrolled in the study (15% of acute
      medical admissions), 43 (37%) were identified by the investigators as likely to
      have normal cardiac enzymes and only one of them had evidence of important
      cardiac ischaemia (median actual length of stay, 3 days). The specificity of the
      protocol was 98%, with a sensitivity of 89%. CONCLUSIONS: A careful clinical
      history taken by experienced junior staff together with two sequential ECGs, can
      identify patients who may be discharged within 24 hours of admission with chest
      pain of uncertain origin. Significant bed savings would result from the
      instigation of this practice, with minimal requirement for extra resources.

PMID- 9597627
TI  - Risk management in the care of medical emergencies after referral to hospital.
AB  - An analysis of 40 medico-legal claims arising from the care of patients admitted
      as medical emergencies showed an excess of young patients (median age 45 years)
      but equal numbers of men and women. Twenty-nine patients died; with optimal
      management, 20 of these patients would have had a good chance of long-term
      survival. Of the 11 who survived, 3 were left with serious neurological deficits
      and 3 underwent intestinal resections that could have been avoided. Further
      analysis revealed probable defects in the organisation of care including:
      inadequate input from experienced clinicians; insufficient use of specialists;
      incorrect interpretation of radiographs and laboratory tests; and inadequate
      assessment of patients before discharge from hospital. It is suggested that there
      is an urgent need to collect and analyse data regarding adverse events in
      hospital medical practice in order to develop optimal organisational structures
      for the care of patients presenting as emergencies.

PMID- 9597628
TI  - Cross cover for physicians: an additional burden.
AB  - OBJECTIVE: To examine the extra burden placed on consultant physicians when
      providing cross cover for colleagues who are absent on annual or study leave.
      METHODS: A questionnaire was sent to 455 consultant physicians with an interest
      in gastroenterology, practising in the UK in October 1996. RESULTS: The response
      rate was 77%, with 350 completed forms returned. Ninety percent of respondents
      participate in the acute intake; they provide 85% of cross cover for their
      colleagues. Only 2% of this burden is carried by the appointment of locums.
      CONCLUSION: Provision of satisfactory cover for inpatients under the care of
      absent colleagues can place serious demands on consultants at a time when their
      specialty commitments are also high. Future manpower planning must take these
      added burdens into consideration.

PMID- 9597629
TI  - A 'fail-safe' screening programme for diabetic retinopathy.
AB  - OBJECTIVE: To improve screening for diabetic retinopathy in a hospital diabetic
      clinic through the use of the audit process. DESIGN: Comparison of an existing
      system of screening for diabetic retinopathy (a specialist optometrist using
      ophthalmoscopy alone) with a new system in which a specialist optometrist
      examined retinal Polaroid photographs taken through pharmacologically dilated
      pupils and combined this with ophthalmoscopy in all cases except when the
      photographs were perfect and definitely showed no retinopathy. In this new
      system, the optometrist could discuss cases of uncertainty with a diabetes
      physician while the patient was still in the clinic with eyes dilated. SETTING:
      Inner city hospital diabetes clinic. SUBJECTS: 289 hospital diabetic clinic
      patients not already attending an ophthalmologist; a consecutive series of 144
      such patients for the first audit, 145 for the repeat audit. MAIN OUTCOME
      MEASURES: Assessment of each screening system against a gold standard. For the
      first audit this was agreement by two of four diabetes physicians, who combined
      examination of the photographs with the findings from dilated ophthalmoscopy, on
      the classification of the retinae of each patient, guided by standard European
      criteria. For the second audit, the gold standard was enhanced by discussing the
      photographs and findings of all patients with an independent ophthalmologist. For
      patients requiring referral, a second ophthalmologist also commented on the case.
      RESULTS: The addition of retinal photography to universal pupil dilatation, and
      the availability of diabetes physician backup to discuss cases of uncertainty,
      greatly increased the optometrists' detection rate. Sensitivities for the first
      (ophthalmoscopy only) and second (ophthalmoscopy plus photography plus
      diabetologist back-up) audits were, respectively, 71.4% vs 100% for sight
      threatening retinopathy, 33% vs 100% for retinopathy requiring six-month review,
      and 40.3% vs 97.2% for any retinopathy (p = 0.002). CONCLUSIONS: Optometrists
      specialising in diabetic retinopathy using Polaroid retinal photography and
      ophthalmoscopy, both through dilated pupils, backed up by experienced
      diabetologists to discuss cases of uncertainty, could form the basis of a
      retinopathy screening service that accurately identifies and categorises
      retinopathy and does not miss sight-threatening cases.

PMID- 9597630
TI  - Elderly patients' satisfaction with hospital care.
AB  - OBJECTIVES: The aim of this study was to assess patient satisfaction with the
      geriatric services of a district general hospital and to examine whether there
      was a difference in satisfaction between patients in hospital and those who had
      been recently discharged. METHODS: A structured and validated patient
      satisfaction questionnaire was administered before discharge to hospitalised
      patients with a mental test score of 8 or more. It was also administered to a
      group of patients in the community who had been discharged from hospital not more
      than 72 hours earlier. The questionnaire was designed to assess seven separate
      areas, and contained 51 statements with which patients were asked to agree or
      disagree. Statistical analysis was by the Mann-Whitney U test and p < 0.05 was
      taken as significant. A total of 134 elderly patients (> 72 years) were surveyed
      over a four-month period. RESULTS: Satisfaction with the hospital geriatric
      service was high in both groups of patients. However, patient satisfaction
      differed between the two groups in three areas: interpersonal aspects; access,
      availability and convenience of the health services; and financial aspects.

PMID- 9597631
TI  - Local research ethics committees' approval in a national population study.
AB  - BACKGROUND: Epidemiological research using patient records faces considerable
      uncertainty regarding requirements for local ethical review, confidentiality of
      data and patient permission. SETTING AND DESIGN: We report the experiences of the
      national study of clustering and geographical variation in anophthalmos and
      microphthalmos, which, from 1994, has been compiling a register of affected
      children born in England since 1988. The information is obtained from clinicians
      and local health authority records without any direct contact with patients or
      their families. RESULTS: Of 110 district health authorities, 47 required ethical
      approval. Only one committee accepted the approval of any other committee.
      Procedures and application forms varied widely. Fewer than one-fifth of the forms
      completed asked about compliance with the Data Protection Act, yet
      confidentiality safeguards must be the foremost ethical issue faced by the study.
      Two committees required that the study inform GPs and two committees required
      that the study obtain parental permission. DISCUSSION: While new mechanisms
      including regional committees are being established, there is an urgent need for
      a standard application form to save time and resources for research. Continuing
      lack of consistency about the need for subject (parental) permission impedes the
      proper design and costing of research.

PMID- 9597632
TI  - Recognition of dermatological conditions by junior doctors on general medical
      wards.
AB  - Although we know something about the prevalence of various dermatological
      conditions in the community, virtually nothing is known about the prevalence and
      type of skin conditions affecting general medical patients in hospital. This has
      important implications for both undergraduate training and the continuing
      education of junior doctors about common skin disorders. In this study we examine
      the prevalence of skin conditions in 100 in-patients on four general medical
      wards, and assess the awareness and diagnostic accuracy of junior doctors
      encountering common dermatological conditions in their patients. Forty-six
      patients had one or more skin conditions, excluding seborrhoeic warts, skin tags,
      benign pigmented naevi and Campbell De Morgan spots. The 16 junior doctors
      correctly diagnosed 64% of common skin conditions that should have been covered
      in the undergraduate curriculum but detected only 43% of the two malignant skin
      lesions (basal cell carcinomas) identified in the study. The presence of skin
      conditions was rarely recorded in the notes, even when the condition was
      potentially relevant to the general medical condition of the patient. This study
      highlights the need for greater awareness of skin disease amongst junior doctors
      in order to avoid unnecessary patient morbidity.

PMID- 9597633
TI  - Medical student education in sleep and its disorders.
AB  - OBJECTIVE: To investigate the pattern of medical student teaching about sleep and
      its disorders in the UK. DESIGN: A questionnaire was sent to organisers of
      preclinical and clinical courses in which aspects of sleep and its disorders
      might appropriately be included. SETTING: All UK medical schools. RESULTS: There
      was an overall 71% response rate, with all medical schools represented. A wide
      variation (80-6%) was seen between departments in the provision of such teaching.
      The median total time given to sleep and its disorders in undergraduate teaching
      as a whole was five minutes, for preclinical teaching 15 minutes, and zero in
      clinical teaching. Teaching was particularly limited on the various types of
      sleep disorder common in clinical practice, and also on non-medication
      treatments. Little consistency was evident in teaching format, recommended
      reading, use of other instructional material and student assessment. Awareness of
      local sleep research or clinics was reported by very few. CONCLUSIONS: As in
      other countries, undergraduate medical teaching is inadequate as a basis for the
      development of competence in diagnosing and treating sleep disorders, which are
      common and cause difficulties in all sections of the population. There is a need
      to correct this deficiency in ways compatible with recent recommended changes in
      medical education.

PMID- 9597634
TI  - Cortisol, hypertension and obesity: the role of 11 beta-hydroxysteroid
      dehydrogenase.
AB  - AME has been a crucial experiment of biology from which much has been learnt
      about corticosteroid hormone action and mineralocorticoid hypertension. 11 beta
      HSD is an important pre-receptor pathway determining corticosteroid hormone
      action. Any tissue expressing 11 beta-HSD1 or 11 beta-HSD2 can clearly modulate
      glucocorticoid and mineralocorticoid action independent of circulating
      concentrations. A series of related enzymes operates in a similar fashion to
      determine hormone action for other members of the thyroid/steroid hormone
      receptor superfamily (e.g. 17 beta-HSD, 25-hydroxyvitamin D 1 alpha-hydroxylase,
      aromatase, 5'-deiodinase, 5 alpha-reductase). Endocrinologists have been obsessed
      with measuring the concentrations of a hormone in the circulation and making
      their decisions on the basis of these results, whether or not that hormone is
      involved in the pathogenesis of a disease process. Such an approach needs to be
      revised, with greater emphasis on considering the action of a hormone within a
      given tissue and, in turn, on the role of these enzymes in the pathogenesis of
      human disease.

PMID- 9597635
TI  - Millennial challenges for medicine and modernity.
AB  - In our polarised modern world, we face enormous challenges that can only be dealt
      with through a new approach to human co-operation. Globally, the crisis in
      medicine poses challenges at micro, meso and macro levels which call for profound
      changes in medical education and in the organisation and accountability of health
      care services. Our view of medicine must extend beyond the domain of the
      physician-patient relationship to include wider aspects of medicine and
      bioethics. This moral perspective demands that the traditional ethical framework,
      with its focus on the sanctity of life, be expanded to recognise the importance
      of quality of life and the need for equitable distribution of resources.

PMID- 9597636
TI  - Platelet transfusion.
AB  - The statement printed below was agreed at a consensus conference on platelet
      transfusion organised by the Royal College of Physicians of Edinburgh and held in
      Edinburgh in November 1997. We publish this statement at the request of the
      organising committee to bring it to the attention of physicians who do not read
      the haematological literature. The statement will also appear in the British
      Journal of Haematology in 1998 with the scientific evidence upon which it is
      based.

PMID- 9597637
TI  - Inflammation, genes and gene therapy.

PMID- 9597638
TI  - Fast-tracking of MI.

PMID- 9597639
TI  - Thyroid nodules.

PMID- 9597640
TI  - The future of general medicine.

PMID- 9597641
TI  - The future of general medicine.

PMID- 9597642
TI  - Symptoms and their management in hospital inpatients.

PMID- 9597643
TI  - Continuing Medical Education.

PMID- 9597644
TI  - Pharmacokinetics of ceftiofur sodium in exotic and domestic avian species.
AB  - The pharmacokinetics of ceftiofur sodium were determined in domestic chicks,
      turkey poults, adult cockatiels (Nymphicus hollandicus), and adult orange-winged
      Amazon parrots (Amazona amazonica) after subcutaneous (chicks and turkey poults
      and intramuscular (i.m.) dosing (cockatiels and Amazon parrots). Turkey poult
      data were best fit to a single exponential model with disappearance half-lives
      (t1/2) of 8.6, 7.4 and 5.6 h after doses of 0.12, 0.24 and 0.48 mg ceftiofur free
      acid equivalents (CFAE)/poult, respectively. Data from chicks were best fit to a
      biexponential model with primary and secondary half-lives of 2.2 and 7.5, 3.7 and
      6.8, and 3.8 and 5.3 h after doses of 0.04, 0.08 and 0.16 mg CFAE/chick,
      respectively. Cockatiel and Amazon parrot data were best fit to a biexponential
      model with primary and secondary half-lives of 0.28 and 2.5, and 0.93 and 7.9 h,
      respectively, after doses of 10 mg CFAE/kg body weight. The maximum concentration
      (Cmax) and area under the concentration time curve (AUC) in chicks and poults
      were dose-proportional. The Cmax for cockatiels was 5.2 micrograms/mL and for
      Amazon parrots was 11 micrograms/mL. Clearance in cockatiels and Amazon parrots
      were 11.3 and 3.8 mL/min/kg, respectively, and reflected the much greater AUC
      seen in Amazon parrots. Clearance values of ceftiofur were similar in chicks and
      Amazon parrots, slightly greater in turkey poults and greatest in cockatiels.
      These results indicate that pharmacokinetic differences must be considered when
      establishing dosage regimens for different avian species.

PMID- 9597646
TI  - Disposition and metabolism of the novel macrolide antibiotic CP-163505 in cattle.
AB  - The plasma pharmacokinetics, lung tissue to plasma concentration ratios, and
      depletion profiles in edible tissue (liver, muscle, kidney, fat and injection
      site) for a single subcutaneous dose of a novel macrolide antibiotic, CP-163505
      (20-[3-dimethylaminopropyl(L-alanyl)amino]-20-deoxo-repromicin), were
      investigated in crossbred beef cattle. Mean peak plasma concentration of 2.5 +/-
      0.4 micrograms/mL, occurring at 0.5 h, was found for CP-163505 following a 5
      mg/kg dose (n = 5). The pharmacokinetic profile consisted of a distribution
      phase, followed by an extended terminal elimination phase (t1/2 of 19 h). The
      disposition of CP-163505 was characterized by distribution from the plasma into
      the tissue resulting in lung to plasma ratios of 103 and 87 at 72 h following a
      single 5 or 10 mg/kg dose, respectively. The depletion of CP-163505 from edible
      tissues was determined following administration of tritiated CP-163505 at a dose
      of 10 mg/kg. On day 42, the liver contained the highest mean concentration of
      total tritium residues, 5.9 +/- 3.4 micrograms/g. CP-163505 was determined to be
      a significant component of the total residues in liver with 72% on day 3 and 50%
      on day 42. Three metabolites of CP-163505 were identified by liquid
      chromatography with mass spectrometry (LC/MS/MS) in liver samples: loss of
      alanine, formation of an hydroxyl derivative, and sulfate addition to the lactone
      ring.

PMID- 9597645
TI  - The effects of ceftiofur sodium (Naxcel) on bovine oocyte and preimplantation
      embryonic development assessed by in vitro embryo production techniques.
AB  - Ceftiofur sodium is a third-generation cephalosporin antibiotic with broad
      spectrum bactericidal activity against Gram-positive and Gram-negative bacteria
      including the beta-lactamase producing strains. In this study, we use in vitro
      techniques to examine the effects of low and high levels of ceftiofur sodium on
      the development of bovine oocytes/embryos during oocyte maturation, oocyte
      fertilization and embryo culture. A total of 8590 oocytes was used in six
      independent experiments, each in a randomized complete block design. Each
      replication within each experiment consisted of oocytes from the same abattoir
      collection of ovaries. There was no difference in embryo development when oocytes
      were exposed to ceftiofur sodium during oocyte maturation or fertilization at low
      (10 and 50 micrograms/mL) or high (100 and 200 micrograms/mL) concentrations.
      However, when fertilized oocytes were exposed to concentrations > or = 50
      micrograms/mL during culture, ceftiofur sodium significantly retarded embryo
      development (e.g. the numbers of ova developing to the morula and blastocyst
      stages were reduced, and a large proportion of embryos were blocked at the 8-cell
      stage). We conclude that ceftiofur sodium does not appear to have detrimental
      effects on oocyte maturation and fertilization. However, long term exposure to
      high dosages of ceftiofur sodium during post-fertilization culture adversely
      affects embryo development in vitro.

PMID- 9597647
TI  - Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor
      subtypes.
AB  - alpha 2-Adrenergic receptor agonists are widely used in veterinary medicine as
      sedative/hypnotic agents. Four pharmacological subtypes of the alpha 2-adrenergic
      receptor (A, B, C and D) have been identified based primarily on differences in
      affinity for several drugs. The purpose of this study was to examine the
      affinities of the sedative agents, xylazine, detomidine and medetomidine at the
      four alpha 2-adrenergic receptor subtypes. Saturation and inhibition binding
      curves were performed in membranes of tissues containing only one subtype of
      alpha 2-adrenergic receptor. The KD for the alpha 2-adrenergic receptor
      radioligand, [3H]-MK-912, in HT29 cells (alpha 2A-), neonatal rat lung (alpha 2B
      ), OK cells (alpha 2C-) and PC12 cells transfected with RG20 (alpha 2D-) were
      0.38 +/- 0.08 nM, 0.70 +/- 0.5 nM. 0.07 +/- 0.02 nM and 0.87 +/- 0.03 nM,
      respectively. Detomidine and medetomidine had approximately a 100 fold higher
      affinity for all the alpha 2-adrenergic receptors compared to xylazine but
      neither agonist displayed selectivity for the alpha 2-adrenergic receptor
      subtypes. These data suggest that available sedative/hypnotic alpha 2-adrenergic
      receptor agonists can not discriminate between the four known alpha 2-adrenergic
      receptor subtypes.

PMID- 9597648
TI  - In vitro metabolism of ceftiofur in bovine tissues.
AB  - The metabolism of ceftiofur in bovine kidney, liver, muscle and lung, and the
      effects of the presence of cystine and glutathione in the media were evaluated
      using S-9 and microsomal tissue fractions. Conversion of ceftiofur to
      desfuroylceftiofur (DFC) was catalyzed by an esterase which was most active in
      kidney, followed by liver. It was not very active in muscle and lung. After DFC
      was liberated, it rapidly bound primarily to tissue proteins (> 56%), and was
      also conjugated to cysteine and glutathione. Production of DFC-cysteine by
      disulfide exchange of DFC with cystine and production of DFC-glutathione by
      conjugation of DFC to glutathione occurred in buffer if glutathione and cystine
      were present in the medium. These conjugations were also observed in incubations
      with tissue fractions, indicating that they were not inhibited by the tissues
      endogenous molecules. In addition, the metabolism of DFC-glutathione to DFC
      cysteine was observed when tissue proteins were present. The metabolism of DFC
      glutathione to DFC-cysteine was faster in kidney than in liver. Metabolites
      devoid of an intact beta-lactam ring were not observed in these in vitro studies.

PMID- 9597649
TI  - Effect of temperature on the pharmacokinetics of benzocaine in rainbow trout
      (Oncorhynchus mykiss) after bath exposures.
AB  - The pharmacokinetics of benzocaine during bath exposures at 1 mg/L were
      determined in rainbow trout acclimated at 6 degrees C, 12 degrees C or 18 degrees
      C for at least 1 month. Individual fish were exposed to benzocaine in a
      recirculating system for 4 h and pharmacokinetic parameters were estimated in a
      unique manner from the concentration of benzocaine in the bath water vs. time
      curve. Elimination from plasma was also determined after the 4 h exposure. The
      uptake clearance and metabolic clearance increased with increased acclimatization
      temperatures (uptake clearance 581 +/- 179 mL/min/kg at 6 degrees C and 1154 +/-
      447 mL/min/kg at 18 degrees C; metabolic clearance 15.2 +/- 4.1 mL/min/kg at 6
      degrees C and 22.3 +/- 4.2 mL/min/kg at 18 degrees C). The apparent volume of
      distribution had a trend for increasing with temperature that was not significant
      at the 5% level (2369 +/- 678 mL/kg at 6 degrees C to 3260 +/- 1182 mL/kg at 18
      degrees C). The elimination half-life of benzocaine in plasma was variable and
      did not differ significantly with temperature (60.8 +/- 30.3 min at 6 degrees C
      to 35.9 +/- 13.0 min at 12 degrees C). Elimination of benzocaine from rainbow
      trout is relatively rapid and even more rapid at higher acclimatization
      temperatures based on calculated metabolic clearances and measured plasma
      concentrations, but was not evident by measurement of terminal plasma half-lifes.

PMID- 9597650
TI  - Pharmacokinetic disposition and arthropathic potential of oral ofloxacin in dogs.
AB  - We examined the relation between the pharmacokinetic disposition and arthropathic
      potential of ofloxacin, a new quinolone antibacterial agent, using both male
      immature (3-month-old) and mature (18-month-old) beagles. Ofloxacin was orally
      administered to these dogs at 20 mg/kg once daily for 8 consecutive days, and the
      animals were killed 2 h after the last treatment. Serum ofloxacin concentrations
      were repeatedly measured on days 1 and 7 by use of high-performance liquid
      chromatography (HPLC), and pharmacokinetic parameters were calculated. In
      addition, on day 8, the drug concentrations in the joint synovial fluid and
      humeral and femoral condyles were measured. Clinico-pathological tests of blood
      and serum or histopathological examination of bone specimens were also performed.
      Arthropathy was macroscopically observed in the cartilage surface of all immature
      dogs, but not in mature dogs. There were, however, no noticeable differences in
      pharmacokinetic parameters between the two age groups of dogs or between single
      and 7-day treatments. In contrast to the occurrence of arthropathic lesions, the
      synovial fluid and condylar drug concentrations in immature dogs was equal to or
      lower than those in mature dogs, suggesting that the pharmacokinetic disposition
      of ofloxacin may not be essential for cartilage lesions.

PMID- 9597651
TI  - The pharmacodynamics of thiopental, medetomidine, butorphanol and atropine in
      beagle dogs.
AB  - This study evaluated the quality of anaesthesia and some of the haemodynamic
      effects induced by a combination of thiopental, medetomidine, butorphanol and
      atropine in healthy beagle dogs (n = 12). Following premedication with atropine
      (ATR, 0.022 mg/kg intravenously (i.v.)) and butorphanol (BUT, 0.22 mg/kg i.v.),
      medetomidine (MED, 22 micrograms/kg intramuscularly (i.m.)) was administered
      followed in 5 min by thiopental (THIO, 2.2 mg/kg i.v.). Heart rate, systolic
      blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood
      pressure (MBP) were monitored continuously with an ECG and direct arterial blood
      pressure monitor. Atipamezole (ATI, 110 micrograms/kg i.v.) was administered to
      half of the dogs (n = 6) following surgery to evaluate the speed and quality of
      arousal from anaesthesia. Anaesthesia was characterized by excellent muscle
      relaxation, analgesia and absence of purposeful movement in response to surgical
      castration. Arousal following antagonism of medetomidine was significantly faster
      (P < 0.05) than in unantagonized dogs. Recoveries were smooth but recovery times
      following atipamezole administration were highly variable among dogs (sternal
      time range 6-38 min, standing time range 9-56 min). Medetomidine caused a
      significant (P < 0.05) increase in SBP, DBP and MBP. Atropine prevented the
      medetomidine induced bradycardia. In conclusion, this combination provided
      adequate surgical anaesthesia in healthy beagle dogs. At the dosages used in this
      study, it seems prudent that this combination should be reserved for dogs free of
      myocardial disease.

PMID- 9597652
TI  - Comparative pharmacokinetics of sulfamethazine in plasma and parotid saliva of
      sheep.
AB  - Salivary output in sheep is large enough to be considered a physiologic body
      fluid compartment. The hypothesis for this work was that pharmacokinetics of
      sulfamethazine in saliva was similar to that in plasma. A reliable technique was
      developed to measure parotid salivary output. Mean output of saliva was 3.18 +/-
      1.04 L from a single parotid gland per day with a mean flow of 2.21 +/- 0.43
      mL/min. Using concentrations of sulfamethazine in parotid saliva made it possible
      to calculate the total passage of sulfamethazine to parotid saliva, which was
      calculated to be 3.5% of the total dose. Pharmacokinetic variables obtained for
      sulfamethazine in plasma and in saliva were closely related (AUC 1408
      micrograms.h/mL and AUC 1484 micrograms.h/mL; Vdarea 0.434 L/kg and Vdarea 0.374
      L/kg; t 1/2 beta 4.30 h and 3.46 h, respectively) and no substantial differences
      were observed. The convenience of using salivary concentrations of sulfamethazine
      for drug monitoring is discussed.

PMID- 9597653
TI  - The regulation of drugs and medicines in horse racing in the United States. The
      Association of Racing Commissioners International Uniform Classification of
      Foreign Substances Guidelines.
AB  - The primary reason for developing the ARCI Uniform Classification of Foreign
      Substances was to give stewards and other racing regulators guidelines to assist
      them in understanding the relative performance effects and general offensiveness
      to the Rules of Racing of various drugs and medications. As such, these
      guidelines have been very useful in the world of racing regulation--officially or
      unofficially--because this classification system, for the first time, places a
      relative number on the inappropriateness of any one of more than 750 agents
      appearing in forensic samples taken from racing horses. The guidelines set up by
      this system established the first framework for dialogue among veterinary
      pharmacologists reviewing these drugs. Prior to development of the guidelines,
      pharmacologists had their own opinions about these agents and their effects on
      performance. The guidelines, however, established a framework for discussion, and
      there has been surprising unanimity about the classification of each of these
      agents. Not only does this classification system provide a useful basis for
      dialogue among experts, it is also useful for regulators, horsemen and other
      laymen, most of whom have little training or experience with drugs and their
      effects on horses. The system is easily understandable and communicates the
      relative possibility of any classified substance to affect the performance of a
      horse. Consequently, the system has made it possible for laymen to understand the
      degree of impropriety of all drugs and medicines with which they may have
      contact. Grouping a large number of drugs into specific classes has greatly
      facilitated discussion about regulations and penalties, and the classification
      system is related to proposed penalty guidelines which were developed in
      parallel. With regard to penalties for Class 1 agents, it is easy to assign and
      defend substantial penalties after examining the guideline statement describing
      the possible performance effects of this group of agents as well as the fact that
      they have no well recognized therapeutic role. Similarly, the relatively modest
      effects of class 4 and 5 agents, combined with the fact that these groups
      encompass a large number of well recognized therapeutic agents, helps in
      understanding the possible presence of trace levels of these agents in post-race
      samples. In summary, the ARCI Uniform Classification of Foreign Substances
      Guidelines condenses data on drugs and medications and places them into a simple
      five class system. This system has made it possible to confidently discuss the
      regulatory implications of the identification of any one of the approximately 750
      classified substances potentially found in forensic samples from a performance
      horse. As such it facilitates both the development and implementation of more
      understandable and equitable regulatory processes.

PMID- 9597654
TI  - Effects of non steroidal anti-inflammatory drugs and sulfonamides on hepatic
      cytochrome P4502C activity in vitro in goats and cattle.

PMID- 9597655
TI  - Lorazepam concentrations in plasma following its intravenous and rectal
      administration in dogs.

PMID- 9597656
TI  - Comparative studies on the pharmacokinetics of norfloxacin in chickens, turkeys
      and geese after a single oral administration.

PMID- 9597657
TI  - Functional-anatomic study of episodic retrieval using fMRI. I. Retrieval effort
      versus retrieval success.
AB  - A number of recent functional imaging studies have identified brain areas
      activated during tasks involving episodic memory retrieval. The identification of
      such areas provides a foundation for targeted hypotheses regarding the more
      specific contributions that these areas make to episodic retrieval. As a
      beginning effort toward such an endeavor, whole-brain functional magnetic
      resonance imaging (fMRI) was used to examine 14 subjects during episodic word
      recognition in a block-designed fMRI experiment. Study conditions were
      manipulated by presenting either shallow or deep encoding tasks. This
      manipulation yielded two recognition conditions that differed with regard to
      retrieval effort and retrieval success: shallow encoding yielded low levels of
      recognition success with high levels of retrieval effort, and deep encoding
      yielded high levels of recognition success with low levels of effort. Many brain
      areas were activated in common by these two recognition conditions compared to a
      low-level fixation condition, including left and right prefrontal regions often
      detected during PET episodic retrieval paradigms (e.g., R. L. Buckner et al.,
      1996, J. Neurosci. 16, 6219-6235) thereby generalizing these findings to fMRI.
      Characterization of the activated regions in relation to the separate recognition
      conditions showed (1) bilateral anterior insular regions and a left dorsal
      prefrontal region were more active after shallow encoding, when retrieval
      demanded greatest effort, and (2) right anterior prefrontal cortex, which has
      been implicated in episodic retrieval, was most active during successful
      retrieval after deep encoding. We discuss these findings in relation to component
      processes involved in episodic retrieval and in the context of a companion study
      using event-related fMRI.

PMID- 9597658
TI  - Functional-anatomic study of episodic retrieval. II. Selective averaging of event
      related fMRI trials to test the retrieval success hypothesis.
AB  - In a companion paper (R. L. Buckner et al., 1998, NeuroImage 7, 151-162) we used
      fMRI to identify brain areas activated by episodic memory retrieval. Prefrontal
      areas were shown to differentiate component processes related to retrieval
      success and retrieval effort in block-designed paradigms. Importantly, a right
      anterior prefrontal area was most active during task blocks involving greatest
      retrieval success, consistent with an earlier PET study by M. D. Rugg et al.
      (1996, Brain 119, 2073-2083). However, manipulation of these variables within the
      context of blocked trials confounds differences related to varying levels of
      retrieval success with potential shifts in subjects' strategies due to changes in
      the probability of target events across blocks. To test more rigorously the
      hypothesis that certain areas are directly related to retrieval success, we
      adopted recently developed procedures for event-related fMRI. Fourteen subjects
      studied words under deep encoding and were then tested in a mixed trial paradigm
      where old and new words were randomly presented. This recognition testing
      procedure activated similar areas to the blocked trial paradigm, with all areas
      showing similar levels of activation across old and new items. Of critical
      importance, significant activation was detected in right anterior prefrontal
      cortex for new items when subjects correctly indicated they were new (correct
      rejections). These findings go against the retrieval success hypothesis as
      formally proposed and provide an important constraint for interpretation of this
      region's role in episodic retrieval. Furthermore, anterior prefrontal activation
      was found to occur late, relative to other brain areas, suggesting that it may be
      involved in retrieval verification or monitoring processes or perhaps even in
      anticipation of subsequent trial events (although an alternative possibility,
      that the late onset is mediated by a late vascular response, cannot be ruled
      out). These findings and their relation to the results obtained in the companion
      blocked-trial paradigm are discussed.

PMID- 9597659
TI  - Effects of healthy aging on the regional cerebral metabolic rate of glucose
      assessed with statistical parametric mapping.
AB  - The aging process is thought to result in changes in synaptic activity reflecting
      both functional and structural cell derangement. However, previous PET reports on
      age-related changes in resting brain glucose utilization (CMRglc) have been
      discrepant, presumably because of methodological as well as subject screening
      differences. In contrast to other studies, which used a region of interest
      approach, the objective of the present work was to determine, by means of the SPM
      software, the changes in regional CMRglc as a function of age in 24 optimally
      healthy, unmedicated volunteers of ages from 20 to 67 years. Global CMRglc showed
      a significant decline with age (approximately 6% per decade, P < 0.05), which
      concerned all the voxels studied save for most of the occipital cortex and part
      of the cerebellum. The most significant effects (P < 0.001) concerned the
      association neocortex in perisylvian temporoparietal and anterior temporal areas,
      the insula, the inferior and posterior-lateral frontal regions, the anterior
      cingulate cortex, the head of caudate nucleus, and the anterior thalamus, in a
      bilateral and essentially symmetrical fashion. The high posterior parietal cortex
      was not sampled in this study. This distribution of changes in CMRglc with age
      may differ from that seen in Alzheimer' disease, where the earliest metabolic
      reduction has been shown to affect the posterior cingulate cortex.

PMID- 9597660
TI  - Measurements of the temporal fMRI response of the human auditory cortex to trains
      of tones.
AB  - Averaged single trials (AST) allowed the functional magnetic resonance imaging
      (fMRI) response to auditory stimuli to be measured at high temporal (1 s) and
      spatial (0.1 cm3) resolution. Using this paradigm we investigated the transient
      signal response to 100-ms tone bursts in trains of between 100 ms and 25.5 s in
      total duration. We have demonstrated that the fMRI response to such auditory
      stimuli is approximately linear for trains of 6 s and longer, but that shorter
      stimuli produce signals that are larger than might be expected from the response
      to the longer stimuli. This nonlinear behavior can be modeled if an adaptive
      response to each stimulus is assumed. A study using a novel paradigm was also
      performed in order to study the influence of scanner noise during fMRI
      experiments on the auditory system response to tones. This study demonstrated
      that the temporal response to 700-ms tone stimuli is modified when performed in
      the presence of scanner gradient noise, the modification being a small but
      significant increase (P < 0.05) in the magnitude of the response. Finally the
      ability to measure the onset of functional activation using the AST method was
      examined. It was found, with the aid of computer simulation that a sampling rate
      of one image per second is adequate to distinguish temporal responses. Using the
      data acquired in this study, onset times were calculated for the auditory cortex,
      and these results are consistent with current models of functional activation.

PMID- 9597661
TI  - A voxel-based analysis of cerebral perfusion in dementia and depression of old
      age.
AB  - Thirty-nine elderly depressed patients as well as 15 demented patients with
      Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high
      resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral
      perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were
      computed to compare early- and late-onset depressed, Alzheimer patients and
      healthy volunteers and to examine associations between regional perfusion and
      clinical and MRI variables. Patients with late-onset depression showed reductions
      in temporal lobe perfusion compared with early-onset depression and controls.
      Alzheimer patients had the expected reduced perfusion in temporoparietal and
      prefontal cortex, as well as basal ganglia, compared with healthy controls.
      Compared with depressed patients, they showed a relative reduction in
      temporoparietal cortex, only. This difference was more pronounced between
      Alzheimer patients and early onset, compared to late-onset patients with
      depression. Periventricular white matter changes on MRI were associated with
      temporal lobe reductions of tracer uptake in depression. In the Alzheimer group,
      deep white matter MRI changes were associated with frontal perfusion deficits.
      Our results support a vulnerability hypothesis, which predicts that patients with
      late-onset depression will show more brain changes than patients with an early
      onset of their illness. Statistical parametric mapping in patients with organic
      psychiatric brain syndromes is feasible and promising as a clinical and research
      method.

PMID- 9597662
TI  - Responsiveness of human cortical activity to rhythmical stimulation: a three
      modality, whole-cortex neuromagnetic investigation.
AB  - We developed numerical indicators to quantify stimulus-related changes in
      cortical magnetic signals recorded from nine healthy subjects while they received
      1- to 2.5-s trains of 15 stimuli (somatosensory, visual, or auditory in separate
      runs) at rates from 6 to 14 Hz, intermingled with 1.6-s pauses. A locking index
      (L) was introduced to quantify how well the responses are time locked to the
      stimuli and a global change factor (GC) to indicate changes in the whole-cortex
      oscillatory activity in the 5- to 25-Hz frequency range. The responses were
      visualized with color-coded images illustrating cortical reactivity for all
      stimulus rates simultaneously. These color maps clearly showed that the modality
      specific cortical signals were enhanced at frequencies corresponding to the
      stimulus rate during the trains. For somatosensory stimulation the activity in
      the vicinity of the somatosensory hand area was enhanced at most stimulus rates,
      suggesting mainly superposition of evoked responses. In individuals with strong
      posterior resting rhythm, visual stimuli typically entrained activity in the
      parietooccipital sulcus at stimulus rates close to the main frequency of the
      spontaneous activity, probably reflecting driving of the intrinsic cortical
      rhythm, whereas in subjects with little spontaneous parietooccipital rhythm the
      cortical signal appeared to be composed mainly of visual evoked responses. No
      modality-specific enhancement was observed during auditory stimulation. During
      the pauses between the trains, the cortical signals were significantly suppressed
      compared with the resting condition: The peak activity (7-13 Hz) was modulated
      within, but also outside, the modality-specific areas, and the signals outside
      the frequency peaks of maximum power were consistently and reproducibly
      suppressed over the whole cortex by all stimuli.

PMID- 9597663
TI  - Suppression of vascular artifacts in functional magnetic resonance images using
      MR angiograms.
AB  - This paper describes a method for processing functional magnetic resonance images
      that suppresses signal changes originating from macroscopic veins visible in
      acquired magnetic resonance angiograms. Finger tapping experiments were performed
      on a 1.5-T scanner and the response was evaluated with voxel-by-voxel cross
      correlation of the time course with a sinusoid at the paradigm frequency. After
      applying a vascular mask to suppress signal changes under macroscopic vessels,
      the vascular and nonvascular subpopulations of the data were compared. By visual
      inspection, the method was found to remove extracortical activation while
      preserving activation in the parenchyma. The observed higher signal amplitudes
      and temporal phase lags of the vascular population agree with theoretical models
      and previous studies. A significant portion of negatively correlated voxels
      occurs adjacent to through-plane vessels. Finally, comparing the centers of mass
      of the activated area before and after vascular suppression showed significant
      shifts in some subjects.

PMID- 9597664
TI  - Premotor and prefrontal correlates of category-related lexical retrieval.
AB  - It has been shown that the retrieval of words denoting visually presented
      concrete entities engages neural systems in the left temporal lobe and that the
      precise pattern of activation within the temporal lobe depends in part on the
      conceptual category to which the entity belongs. Here, we used [15O]water
      positron emission tomography to test the hypothesis that the pattern of
      activation associated with word retrieval in left frontal lobe would also be
      related to conceptual category. The design entailed the performance of three
      tasks requiring the retrieval of words denoting animals, tools, and unique
      persons. The visual stimuli were presented at different rates, to produce equal
      performance success across categories, a feature which also had the effect of
      equalizing the proportion of scan time spent in mental search. All three word
      retrieval tasks activated the left inferior frontal gyrus, but they differed in
      their recruitment of two other premotor and prefrontal areas. Activity in a
      portion of the middle frontal gyrus, corresponding to Brodmann area 46, bore a
      linear relation to response latency and may index the extent of mental search.
      This region was most active when subjects named persons. Activity in the anterior
      bank of the precentral gyrus, along the inferior and middle frontal gyri, was
      most marked for naming tools. This region overlaps the area activated when
      subjects generate words for actions. We suggest that it is engaged by the
      retrieval of words denoting actions or objects with characteristic actions. The
      data presented here provide additional support for the notion that "nonclassical"
      language areas in extrasylvian frontal and temporal regions mediate word
      retrieval and that the pattern of their engagement relates to conceptual
      category.

PMID- 9597665
TI  - Mapping neural interactivity onto regional activity: an analysis of semantic
      processing and response mode interactions.
AB  - Neuroimaging studies of cognition have typically been designed to identify brain
      regions that are active during a cognitive process. However, identifying how
      brain regions interact may be equally important. In a recent study we found that
      the pattern of activation associated with a semantic task differed depending on
      how subjects made a response, suggesting that there was an interaction between
      the neural systems underlying response mode and semantic processing (J. M.
      Jennings et al., 1997, NeuroImage 5, 229-239). This result raises two important
      questions, which we examined here: (1) How did the regions underlying semantic
      performance influence one another, or interact, to produce a different pattern of
      activation in each case? (2) What can be learned about the neurobiology of
      semantic processing when different regions are identified as a function of
      response? We addressed these questions using structural equation modeling. This
      technique produced functional network models representing the effect of different
      regions on each other during the semantic task for each response. A common
      network of regions associated with semantic processing was observed and included
      the left inferior frontal and left superior temporal cortices, with other regions
      brought into that network depending on response (e.g., right middle frontal).
      Moreover, changes in the influences among these regions across response condition
      predicted the pattern of activation found previously. These results show how an
      arbitrary response can affect the neural pathways associated with a cognitive
      process, likely due to the parallel and reentrant organization of the brain, and
      emphasize the importance of examining functional connections when studying
      cognition.

PMID- 9597666
TI  - Mapping the cingulate cortex in response selection and monitoring.
AB  - Many cognitive tasks have activated areas of the cingulate cortex. These include
      error detection, divided attention, conflict, and word generation tasks. However,
      the exact area of the cingulate found to be active has differed. This could be
      due to difference in subjects, laboratories, data analysis, or task conditions.
      The current study uses two very different tasks known to activate the cingulate
      and compares data from the same subjects and same trials to see whether there are
      temporal and spatial distinctions in cingulate activations. The tasks chosen were
      generation of the use of a noun and feedback that an error was made in the time
      window required for generation. High-density electrical recording was used to
      trace the time course of cingulate activation in the difference waves between
      correct and error feedback and between generate and repeat. Both tasks produced
      activity that is consistent with cingulate activation. However, the two tasks
      produced activity in different areas. These data are consistent with the idea
      that differences in areas of the cingulate activated differ between cognitive
      tasks and are not merely due to subject and laboratory differences.

PMID- 9597668
TI  - Plasma and platelet amino acid concentrations in patients affected by major
      depression and under fluvoxamine treatment.
AB  - Plasma and platelet levels of 18 amino acids were measured in 29 outpatients
      (mean age +/- SD 47.41 +/- 10.85 years; 14 F, 15 M) affected by major depression
      (DSM IV) and in 28 healthy volunteers (mean age 42.46 +/- 14.19 years; 12 F, 16
      M). Plasma and platelet levels of amino acids tended to be higher in depressed
      patients than in healthy controls. In particular, glutamate, taurine and lysine
      plasma levels and aspartate, serine and lysine platelet levels were significantly
      higher. Tryptophan/large neutral amino acids ratio (trp/LNAAs) was significantly
      lower in depressed patients. Fluvoxamine treatment did not influence plasma and
      platelet levels of amino acids or trp/LNAAs ratio.

PMID- 9597669
TI  - Inflationary tendencies in judging the yield of depression research.
AB  - The mood around mood disorders is one of optimism. Progress in diagnosis and
      treatment is generally felt to be considerable. Zeitgeist rests on convictions.
      In this case the main supporting convictions are the following: depression is a
      very frequent disorder and its diagnosis has improved greatly; we dispose of more
      or less specific agents to control depression: biological psychiatric research
      made great strides, particularly in the field of affective disorders; new
      antidepressants are properly tested before being clinically introduced. Each of
      these convictions is critically analysed. It is concluded that each of these
      claims is either a half-truth or not true. Apparently reality awareness and
      reality testing are out of balance. This harms the prospects of research,
      particularly biological research. Ways to avoid the stalemate are discussed.

PMID- 9597667
TI  - Smooth pursuit eye movement dysfunction in substance-dependent patients:
      mediating effects of antisocial personality disorder.
AB  - Smooth pursuit eye movements were evaluated in 21 healthy volunteers and 126
      patients meeting criteria for one of the following DSM-III-R dependence
      diagnoses: alcohol (n = 10), cocaine (n = 44), heroin (n = 34), or dual alcohol
      and cocaine (n = 38). A significant reduction in tracking accuracy was found in
      the heroin and the dually dependent groups relative to controls. Interestingly,
      the eye movement dysfunction in the drug-dependent groups was no longer
      detectable when the effects of antisocial personality disorder were statistically
      removed. The magnitude of the dysfunction also correlated with several antisocial
      personality-related features, including an increased number of criminal charges
      and months of incarceration, increased problems associated with drug abuse, and
      lower intellectual functioning. The relationship demonstrated presently between
      antisocial personality disorder and eye movement dysfunction may have
      implications beyond studies of substance dependence.

PMID- 9597670
TI  - Platelet 5-HT and plasma cortisol concentrations after dexamethasone suppression
      test in patients with different time course of schizophrenia.
AB  - Platelet 5-HT and plasma cortisol concentrations were determined in 59
      schizophrenic patients with different time course of illness before and after
      dexamethasone suppression test (DST). An abnormal DST (nonsuppression) was
      observed in 51% of patients. In these patients basal cortisol and platelet 5-HT
      concentrations were higher than in patients with normal DST. After DST, plasma
      cortisol levels were higher in nonsuppressors with intermittent and intermittent
      chronic time course, whereas platelet 5-HT concentrations were increased in
      nonsuppressors with intermittent-chronic time course. The results suggest that
      schizophrenic patients have dysregulated hypothalamic-pituitary-adrenal axis as
      shown by a high rate of DST nonsuppression, and that nonsuppressors showed
      hypercortisolemia and hyperserotonemia independent of the time course of
      schizophrenia. No significant association between DST and time course of the
      illness was found.

PMID- 9597671
TI  - Predictors of lithium treatment responsiveness in bipolar patients. A two-year
      prospective study.
AB  - Twenty-nine bipolar patients were assessed before the start of lithium therapy to
      study the prognostic criteria of long-term response to therapy. Assessment
      included clinical and demographic data and laboratory tests administered before
      and 2-5 days after initiation of therapy. The tests included calcium and
      magnesium serum levels, and thyroid hormonal status. Patients were followed up
      for 2 years. None of the single variables predicted the response to lithium
      therapy, but a combination of clinical and demographic variables, used in a
      discriminant function analysis, correctly identified 78.9% of responders.
      Multiple regression analysis predicted 46.2% of the outcome. The strongest
      univariate predictors were mood quality, illness duration, and substance abuse.

PMID- 9597672
TI  - Single-blind, placebo phase-in trial of two escalating doses of selegiline in the
      chronic fatigue syndrome.
AB  - AIM: To perform a clinical trial of selegiline in 25 patients with chronic
      fatigue syndrome (CFS) where patients were told they would receive placebo or
      active agent at different times during the 6-week trial. We chose selegiline, a
      specific monoamine oxidase (MAO) B receptor inhibitor, because a prior trial of
      lowdose phenelzine, a nonspecific MAO inhibitor, showed a small but significant
      therapeutic effect. METHODS: Questionnaires comprised of 19 tests of mood,
      fatigue, functional status and symptom severity were collected at the start and
      end of the trial as well as 2 weeks after its start. The trial was done in three
      2-week blocks: in the first, 2 placebo pills were given per day; in the next, one
      5-mg tablet of agent and one placebo were given per day, and in the last, a 5-mg
      tablet of agent was given twice a day. The plan was to compare the changes in the
      19 tests during the placebo phase to those found in the active treatment phase in
      19 patients completing the trial. FINDINGS: Significant improvement in 3
      variables-tension/anxiety, vigor and sexual relations-was found. A significant
      pattern of improvement compared to worsening was found for the 19 self-report
      vehicles during active treatment as compared with placebo treatment. Evidence for
      an antidepressant effect of the drug was not found. CONCLUSIONS: Selegiline has a
      small but significant therapeutic effect in CFS which appears independent of an
      antidepressant effect.

PMID- 9597673
TI  - Amperozide influences feeding independently of 5-HT2A receptor antagonism.
AB  - Amperozide has been biochemically classified as a selective 5-HT2A (serotonin
      type 2A) receptor antagonist. However, research on the behavioral effects of
      amperozide suggests the possibility of other mechanisms. The present study in the
      male rat is an investigation of the effect of amperozide on feeding, a behavior
      which can be inhibited by 5-HT2A agonists such as 1-(2,5-dimethoxy-4-iodophenyl)
      2-aminopropane (DOI). Experiments revealed that amperozide acted to inhibit
      feeding behavior both when administered alone and when administered in
      combination with DOI. These results are inconsistent with 5-HT2A receptor
      antagonism by amperozide. Further experiments suggested that amperozide may be
      acting via alpha 2-adrenergic or 5-HT1A receptors to inhibit feeding. These
      studies imply that amperozide's selective 5-HT2A antagonistic activity is
      behaviorally specific.

PMID- 9597674
TI  - Effects of pemoline on spontaneous and event-related electrical activity of the
      brain.
AB  - The effect of pemoline on the electrical activity of the brain
      (electroencephalogram, EEG) was studied in relation to time since sleep and time
      of day in 6 healthy subjects carrying out periods of work lasting 18 h. Power of
      the spontaneous EEG increased with time since sleep and amplitude of the P3 event
      related response decreased. The changes may be interpreted as the reduction in
      alertness with time awake. In contrast, pemoline decreased power of the
      spontaneous EEG and increased the amplitude the P3 response, effects that are
      consistent with improved alertness. The changes in brain activity were paralleled
      by effects on performance, in terms of percentage of correct responses and
      reaction time. Performance decreased with time awake, and was improved by
      pemoline compared with placebo. The drug counteracted the adverse effects of time
      since sleep, with the beneficial effect of the drug persisting over the 18-hour
      period of work. The findings emphasise that spontaneous and event-related
      activity of the EEG may be used both to complement measures of performance in the
      laboratory and to assess behaviour in occupational situations where performance
      testing is impractical.

PMID- 9597675
TI  - Estrogens and women with breast cancer.

PMID- 9597677
TI  - Nancy Reagan's choice of mastectomy seems to have influenced many breast cancer
      patients.

PMID- 9597676
TI  - Small-cell lung cancer: treatment progress and prospects.
AB  - Although small-cell lung cancer (SCLC) represents only 20% of all lung cancer
      cases in the United States, it is the most lethal subtype. Combination
      chemotherapy unequivocally offers the best chance for improved survival in SCLC.
      Either PE (platinum plus etoposide) or CAV (cyclophosphamide, Adriamycin, and
      vincristine) is a reasonable first-line therapy. Alternating PE with CAV does not
      appear to be significantly superior to PE or CAV alone. Increasing dose
      intensity, although sometimes associated with higher response rates, does not
      appear to significantly improve survival and should not be used outside of a
      clinical study. Several new agents with novel mechanisms of action show promise
      in treating SCLC. These include: gemcitabine (Gemzar), paclitaxel (Taxol),
      docetaxel (Taxotere), topotecan (Hycamtin), and irinotecan (Camptosar). Given the
      poor survival and response rates in relapsed patients and the chemoresponsiveness
      of SCLC, patients with newly diagnosed extensive disease should be encouraged to
      enroll in phase I or II trials. Thoracic radiotherapy confers a small survival
      advantage in limited-stage SCLC patients. Although prophylactic cranial
      irradiation does not significantly improve survival, it does reduce central
      nervous system (CNS) recurrences with minimal long-term sequelae. Surgery should
      be considered only for: (1) resection of a solitary pulmonary nodule, which must
      be followed by adjuvant chemotherapy; and (2) resection of an unresponsive chest
      tumor, which may harbor a non-small-cell lung cancer component.

PMID- 9597678
TI  - Management of malignant tumors of the salivary glands.
AB  - Results of treatment for patients with salivary gland carcinoma have improved in
      recent years, most likely due to earlier diagnosis and the use of more effective
      locoregional therapy. Salivary gland tumors are treated surgically, often in
      conjunction with postoperative radiation therapy when the tumor is malignant.
      Good results rest strongly on the performance of an adequate, en bloc initial
      resection. Radical neck dissection in indicated in patients with obvious cervical
      metastasis, and limited neck dissection may be appropriate in patients with
      clinically negative nodes in whom occult nodal involvement is likely.
      Postoperative radiation therapy should be administered when the tumor is high
      stage or high grade, the adequacy of the resection is in question, or the tumor
      has ominous pathologic features. Neutron beam therapy shows promise in
      controlling locoregional disease but requires further study. No single
      chemotherapeutic agent or combination regimen has produced consistent results. At
      present, chemotherapy is clearly indicated only for palliation in symptomatic
      patients with recurrent and/or unresectable cancers. Patients with salivary gland
      carcinomas must be followed for long periods, as recurrence may occur a decade or
      more following therapy. Distant metastasis appears to occur in approximately 20%
      of patients.

PMID- 9597679
TI  - Clinical trials referral resource. Tumor Vaccine Trials.

PMID- 9597680
TI  - Quality of life in patients with low-grade non-Hodgkin's lymphoma.
AB  - Low-grade non-Hodgkin's lymphoma (NHL) is an indolent form of the disease with a
      generally slow course of progression. Although still usually incurable, low-grade
      disease has shown responsiveness to some of the newer chemotherapeutic and
      nonchemotherapeutic treatment options. However, since cure remains elusive, and
      since many patients with lowgrade NHL may have few or even no symptoms initially,
      the decision about whether or not to initiate treatment logically must include
      quality-of-life (QOL) issues. This paper summarizes clinical and diagnostic
      characteristics of low-grade NHL that have some bearing on QOL considerations.
      Adverse effects of the more common treatment approaches are discussed according
      to their QOL implications, illustrating the relevance of QOL to the clinical
      management of low-grade disease. Finally, data from an ongoing study using the
      Functional Assessment of Cancer Therapy (FACT) measurement system are presented.
      These data offer a basis for comparing the QOL of patients with NHL to that of
      individuals with other solid tumors, and also illustrate the effects of
      chemotherapy on QOL.

PMID- 9597681
TI  - Prostate-specific antigen: chronology of its identification.

PMID- 9597682
TI  - Substance abuse issues in cancer patients. Part 2: Evaluation and treatment.
AB  - The relationship between the therapeutic use of potentially abusable drugs for
      symptom control and the multifaceted nature of abuse and addiction is extremely
      complex. Research is only beginning to elucidate the nature of this relationship
      and its clinical implications. At present, practical management is based
      primarily on clinical experience and anecdotal observations. In part I of this
      two-part series (published last month), the authors explored the epidemiology of
      substance abuse in the cancer population, provided definitions of addiction and
      abuse appropriate for the oncology setting, and offered guidelines for the
      assessment of aberrant drug-taking behavior. In this second part, the authors
      provide recommendations for the evaluation and treatment of patients with cancer
      who have a history of substance abuse. Suggested therapeutic goals are outlined,
      and plans for inpatient and outpatient management and detailed.

PMID- 9597683
TI  - Keys to success of BMT programs in managed care era.

PMID- 9597684
TI  - AIDS among persons age > or = 50 years--United States, 1991-1996.

PMID- 9597685
TI  - Pregnancy after breast cancer: from psychosocial issues through conception.
AB  - Women face numerous issues if they either contemplate childbearing or become
      pregnant after the diagnosis of breast cancer. Based on a search of the English
      medical literature from 1966 to 1997, we make the following conclusions regarding
      pregnancy after breast cancer: (1) Sexual function is not affected by the
      decision to treat breast cancer by breast conservation vs mastectomy. (2)
      Infertility after breast cancer treatment is directly proportional to patient age
      and the use and dose of alkylating agents. There is no conclusive information on
      the effects of duration, dose intensity, schedule, or route of administration of
      chemotherapy on subsequent fertility. (3) There appears to be no increase in
      birth defects in children whose parents were exposed to chemotherapy earlier in
      life. (4) Milk production of the irradiated breast is likely to be limited. Also,
      breastfeeding appears to decrease the risk of breast cancer. (5) With respect to
      monitoring pregnant women for breast cancer recurrence, in general the
      recommendations made by the American Society of Clinical Oncology (ASCO)
      regarding monitoring in nonpregnant women should be followed. (6) Pregnancy does
      not increase the risk of recurrent breast cancer. (7) Adjuvant tamoxifen
      (Nolvadex) therapy has adverse effects on pregnancy in vivo and in laboratory
      animals. No reports exist on the effects of tamoxifen on human pregnancy.

PMID- 9597686
TI  - Enzyme that detoxifies cancer drug linked to risk of Alzheimer's disease.

PMID- 9597687
TI  - Herpes simplex virus investigated for treatment of brain tumors.

PMID- 9597688
TI  - Inhibition of anaphylaxis by sulfasalazine in rats.
AB  - We studied the effect of sulfasalazine on anaphylaxis. Sulfasalazine dose
      dependently inhibited systemic anaphylaxis induced by compound 48/80 in rats.
      Sulfasalazine also inhibited local anaphylaxis activated by anti-dinitrophenyl
      (anti-DNP) IgE. Moreover, sulfasalazine dose-dependently inhibited histamine
      release in the peritoneal mast cells activated by compound 48/80 or anti-DNP IgE.
      All of these effects were comparable to those of the disodium cromoglycate
      (reference drug) tested. When sulfasalazine was added, the level of cAMP in rat
      peritoneal mast cells transiently and significantly increased about 6-fold
      compared with that of basal cells. Our studies provide evidence that
      sulfasalazine may be beneficial in the treatment of anaphylaxis.

PMID- 9597689
TI  - Pharmacological modulation of LPS-induced MIP-1 alpha production by peripheral
      blood mononuclear cells.
AB  - In the present study, we investigated the effects of some anti-asthmatic drugs on
      the production of the CC chemokine, macrophage inflammatory protein-1 alpha (MIP
      1 alpha), in response to lipopolysaccharide (LPS) by peripheral blood mononuclear
      cells (PBMC). MIP-1 alpha production was induced by LPS in a concentration
      dependent fashion and reached the maximum at 10 micrograms/ml LPS (27.5 +/- 2.3
      ng MIP-1 alpha/10(6) PBMC). At a submaximal concentration of LPS (1
      microgram/ml), the release of MIP-1 alpha increased with time and reached the
      maximum 24 h after LPS stimulation. Actinomycin D and cycloheximide inhibited MIP
      1 alpha production completely, but glucocorticoids did not completely inhibit MIP
      1 alpha production, with a maximum inhibition of 70%. We examined the effect of
      beta-stimulants and phosphodiesterase inhibitors, which upregulate intracellular
      cyclic AMP levels, on MIP-1 alpha production. When PBMC were treated with beta
      stimulants alone, beta-stimulants showed a slightly inhibitory effect on MIP-1
      alpha production. However, the coadministration of roliplam significantly
      potentiated the inhibitory effect of beta-stimulants on MIP-1 alpha production.
      Moreover, db-cAMP suppressed MIP-1 alpha production dose-dependently. The above
      data indicate that the production of MIP-1 alpha is regulated by cyclic AMP and
      that cyclic AMP could provide a useful target for therapeutic treatment in
      asthmatic diseases and other diseases where MIP-1 alpha is involved in their
      etiology.

PMID- 9597690
TI  - Inhibitory effect of TRK-530 on inflammatory cytokines in bone marrow of rats
      with adjuvant arthritis.
AB  - TRK-530 is a novel synthetic bisphosphonate compound which exhibits inhibitory
      activity in the rat adjuvant arthritis (AA) model. We found that, during AA
      development, the concentrations of cytokine-induced neutrophil chemoattractant-1
      (CINC-1) and tumor necrosis factor alpha (TNF-alpha) in the bone marrow
      increased, and that administration of TRK-530 decreased the concentrations of
      these cytokines. The suppression of these concentration increases paralleled the
      inhibition of paw edema. Paw edema inhibition by TRK-530 in rat AA may be the
      result of decreasing CINC-1 and TNF-alpha concentrations.

PMID- 9597691
TI  - Inhibitory effects of TRK-530 on rat adjuvant arthritis.
AB  - TRK-530 is a novel bisphosphonate derivative. We examined the anti-inflammatory
      effects of TRK-530 on adjuvant arthritis (AA) rats. When TRK-530 at a dose of 2.5
      mg/kg was administered for 2 weeks to AA rats, it inhibited destructive changes
      in arthritic joints such as paw edema, bone loss and joint degeneration. TRK-530
      also inhibited splenomegaly and suppressed the increase in serum sialic acid
      which is measured as a systemic parameter of inflammation. To clarify the
      inhibitory mechanism of TRK-530, interleukin-1 (IL-1)-like activities of resident
      peritoneal macrophages in AA rats given TRK-530 were compared with those of
      control rats. We found that TRK-530 inhibited IL-1-like activity induced by
      bacterial lipopolysaccharide 6 weeks after administration when the IL-1-like
      activities of control rats were still at high levels. These findings suggest that
      TRK-530 exerts anti-inflammatory activities in AA rats.

PMID- 9597692
TI  - Kinetic properties of nitric oxide synthase in cerebral cortex and cerebellum of
      morphine tolerant mice.
AB  - The effects of chronic morphine administration on the kinetics of nitric oxide
      synthase (NOS) activity were determined in the mouse cerebral cortex and
      cerebellum. Male Swiss-Webster mice were implanted subcutaneously with morphine
      pellets each containing 25 mg of morphine base for 3 days. Mice implanted with
      placebo pellets served as controls. NOS activity was determined by measuring the
      rate of conversion of [3H]arginine to [3H]citrulline. Morphine pellet
      implantation increased NOS activity in the cerebral cortex and cerebellum.
      Analysis of the Eadie-Hofstee plot indicated that the Vmax of NOS in the cortex
      and cerebellum was 140 and 228 pmol [3H]citrulline formed/min/mg protein and the
      Km values were 9.3 and 10.1 mumol/l, respectively. Mice implanted with morphine
      pellets had higher Vmax values in both the cortex and cerebellum, but the Km
      values did not differ from those of control mice implanted with placebo pellets.
      It is concluded that chronic treatment with morphine increases NOS activity in
      the brain without modifying its substrate affinity.

PMID- 9597693
TI  - Involvement of nitric oxide synthase in proteinuria associated with chronic renal
      disease in rats.
AB  - The present study demonstrates that the nitric oxide synthase inhibitor,
      aminoguanidine, can attenuate the proteinuria observed in a predominantly
      noninflammatory model of chronic renal disease in the rat. These data suggest
      that nitric oxide synthase may be involved in progressive renal disease.

PMID- 9597694
TI  - Pedigree analysis of a subject with abnormally slow renal elimination of 6
      hydroxychlorzoxazone.
AB  - The family of an unusual subject was studied. When tested with chlorzoxazone (CX;
      250 mg p.o.) on four separate occasions 5 years ago, this subject showed
      abnormally slow renal elimination of 6-hydroxychlorzoxazone (HCX), the primary CX
      metabolite. Since rates of CX biotransformation to HCX have served as a probe of
      the important cytochrome P450 isozyme, CYP 2E1, it was of interest that this
      unusual subject had normal conversion of CX to HCX. The present study revealed
      that over the past 5 years this subject accelerated his renal rate of HCX
      elimination which now lies at the slow end of the curve for normal subjects. His
      wife and 5 children all had more rapid rates than he for renal HCX elimination.

PMID- 9597695
TI  - A comparison of spasmogenic and relaxant responses in aortae from C57/BL/KsJ
      diabetic mice with those from their non-diabetic litter mates.
AB  - We have investigated the responsiveness of thoracic aorta from the C57/BL/KsJ
      db/db mouse (a model of type II diabetes) using a small-vessel myograph. The
      maximum tension developed in response to phenylephrine was greater in diabetic
      mice compared with non-diabetic (+/?) mice (2.7 +/- 0.1 and 1.8 +/- 0.1 mN/mm,
      respectively). Responses to phenylephrine were enhanced in tissues from both
      phenotypes when preincubated with L-NAME (100 mumol/l) and after the addition of
      oxyhaemoglobin (3 mumol/l), suggesting that endogenous NO release occurs in both.
      The maximum relaxation to carbachol was less in db/db mice (32 +/- 4%) than in
      +/? mice (49 +/- 5%) whilst that to sodium nitroprusside was similar (> 90%).
      However, the concentration-effect curve to both vasorelaxants in db/db mice lay
      to the right of that in the +/? mice. These results suggest that the
      responsiveness of the vasculature is altered in the db/db mouse. Since this mouse
      is a model of type II diabetes this may be a consequence of hyperglycaemia and/or
      insulin resistance.

PMID- 9597697
TI  - Pull-through procedures for Hirschsprung's disease. Introduction.

PMID- 9597696
TI  - Liver dihydropyrimidine dehydrogenase activity in human, cynomolgus monkey,
      rhesus monkey, dog, rat and mouse.
AB  - Interspecies differences in dihydropyrimidine dehydrogenase (DPD), the initial
      and rate-limiting enzyme in pyrimidine degradation, were assessed in cytosol from
      livers isolated from human, monkey, dog, rat, and mouse. Hepatic DPD activity was
      measured by an HPLC assay with on-line radioactivity detection, using 14C-5
      fluorouracil as a substrate. Activity was highly variable within each species and
      significant interspecies differences in liver DPD activity were observed. The
      order of activity was mouse > rat > human > dog > or = cynomolgus monkey > rhesus
      monkey. These data suggest that careful selection must be made when choosing in
      vivo models of human DPD for the preclinical development of novel
      fluoropyrimidine anticancer agents and DPD inhibitors.

PMID- 9597698
TI  - Swenson procedure for the treatment of Hirschsprung's disease.

PMID- 9597699
TI  - The Duhamel procedure for Hirschsprung's disease.

PMID- 9597700
TI  - Endorectal pull-through with primary anastomosis for Hirschsprung's disease.

PMID- 9597701
TI  - Primary pull-through in the newborn.

PMID- 9597702
TI  - Fundoplication controversies in the treatment of pediatric gastroesophageal
      reflux disease. Introduction.

PMID- 9597703
TI  - Nissen fundoplication for gastroesophageal reflux disease in infants and
      children.

PMID- 9597704
TI  - Thal fundoplication for pediatric gastroesophageal reflux disease.

PMID- 9597705
TI  - Toupet fundoplication for pediatric gastroesophageal reflux disease.

PMID- 9597706
TI  - Controversies in the management of esophageal atresia without fistula.
      Introduction.

PMID- 9597707
TI  - Delayed primary esophageal anastomosis for pure esophageal atresia.

PMID- 9597708
TI  - Esophageal substitution.

PMID- 9597709
TI  - Esophageal replacement for atresia without fistula.

PMID- 9597710
TI  - The distribution of body water and general approach to the patient.
AB  - This article discusses some of the basic issues concerning fluid therapy in small
      animals. It is hoped that the reader is able to assess the fluid needs of a dog
      or cat presented for veterinary treatment. The remaining articles address
      particular fluid compositions and fluid choices in patients with a variety of
      diseases and electrolyte imbalances.

PMID- 9597711
TI  - The various types of parenteral fluids and their indications.
AB  - Assessment of hydration and perfusion is essential in patient evaluation. The
      acid-base and electrolyte disturbances that accompany many illnesses should also
      be considered. The duration of illness and body systems involved are also of
      major importance in patient evaluation. Fluid therapy is an important and
      potentially life-saving treatment of many and varied problems. The clinician must
      be able to assess the patient and determine whether the intravascular or
      extravascular compartments, or both, are deficient. Of primary concern is the
      status of the intravascular volume, then restoration of total body water and
      electrolytes. Fluid therapy is divided into three phases; the emergency phase,
      the rehydration phase, and the maintenance phase; not all patients require the
      three-phase therapy. The clinician must also be able to select (1) the
      appropriate solution to treat the volume deficit and correct the acid-base and
      electrolyte abnormalities and (2) the rate of administration to optimize outcome.
      Therefore, knowledge of electrolyte composition in plasma and of the various
      types of commercially available fluids is essential in order to select the
      appropriate therapy for the individual animal. In addition to the therapeutic
      aspects of fluid therapy, a knowledge of the side effects and complications of
      inappropriate fluid selection and rate of delivery is also important. With the
      individual requirements of each patient seen in a practice, the prescription
      approach to parenteral fluid therapy will optimize patient response to this
      extremely important aspect of overall patient management as well as make the
      practice of fluid therapy intellectually stimulating. This article has introduced
      the clinician to the parenteral fluids available and their indications in
      veterinary patients; it also contains a discussion of how to utilize preferred
      solutions for treatment of specific diseased states. Although there are definite
      "right" and "wrong" fluids to select for specific problems, there also remains
      individual preference in fluid choice, which is based on appropriate laboratory
      data and the practitioner's clinical judgment of the status of the individual
      patient vis-a-vis the spectrum of its disease. Recommendations for selection of
      different fluid types to treat similar conditions are usually based on these
      variables.

PMID- 9597712
TI  - Hyponatremia.
AB  - The serum sodium concentration reflects the osmolality of the extracellular fluid
      and provides no direct information about total body sodium content. Patients with
      hyponatremia may have decreased, normal, or increased total body sodium content.
      The first step in the approach to the patient with hyponatremia is measurement of
      plasma osmolality. Hyponatremia with normal plasma osmolality results from
      hyperlipemia or hyperproteinemia, whereas hyponatremia with increased plasma
      osmolality results from hyperglycemia or mannitol infusion. Patients with
      hyponatremia and decreased plasma osmolality may be hypovolemic, hypervolemic, or
      normovolemic. The volume status of the patient is best determined by history,
      physical examination, and a few ancillary tests (e.g., total plasma protein
      concentration, hematocrit, blood pressure, central venous pressure). The clinical
      signs of hyponatremia are related more to the rapidity of onset than to the
      severity of the associated plasma hypoosmolality and reflect influx of water into
      the central nervous system. The main goals of treatment in hyponatremia are to
      diagnose and manage the underlying disease and, if necessary, to increase serum
      sodium concentration and plasma osmolality.

PMID- 9597713
TI  - Hypernatremia and hypertonic syndromes.
AB  - Hypernatremia is the most common cause of hypertonicity in small animal medicine.
      Despite this fact, severe hypernatremia is an uncommon clinical entity in dogs
      and cats. The causes of hypernatremia are excessive water loss and increased
      sodium intake. Clinical signs are most often related to CNS dysfunction. Severe
      hypernatremia should be considered a life-threatening situation and treated as
      such. Initial fluid therapy should be given with care according to the rate of
      onset of hypernatremia, as deterioration of the animal's condition is a common
      sequela. The determination of the cause of hypernatremia and the treatment can be
      both challenging and rewarding. The other notable hypertonic syndrome in small
      animal medicine is hyperosmolar nonketotic diabetes mellitus. Judicious
      management of this disease with fluid therapy and insulin is the standard
      therapy. An understanding of the pathophysiology is essential to their diagnosis
      and appropriate medical management.

PMID- 9597714
TI  - Clinical disorders of potassium homeostasis. Hyperkalemia and hypokalemia.
AB  - Potassium plays an important role in cell metabolism and membrane excitability.
      Disorders of potassium balance can have profound clinical effects, particularly
      on the cardiovascular and neuromuscular systems. Chronic hyperkalemia invariably
      results from impaired renal potassium excretion. Hyperkalemia can be a
      potentially life-threatening disturbance requiring emergency intervention.
      Treatment is usually directed at correcting the defect in potassium excretion.
      Hypokalemia has become closely linked with in cats. Clinical signs include muscle
      weakness and renal dysfunction, which usually respond well to oral potassium
      supplementation.

PMID- 9597715
TI  - Hypercalcemia and hypermagnesemia.
AB  - Hypercalcemia and hypermagnesemia occur infrequently in small animal patients.
      Specific clinical signs usually do not accompany these electrolyte disorders, and
      their presence is often recognized only after reviewing serum chemistry profile
      results. The etiologies, clinical signs, and therapies for each electrolyte
      disorder are discussed in this article. Treatment of these disorders is aimed at
      correcting the underlying disease process and enhancing the removal of calcium or
      magnesium from the body. In severe cases, rescue therapies and resuscitative
      measures are required to stabilize the patient.

PMID- 9597716
TI  - Hypocalcemia and hypomagnesemia.
AB  - The occurrence of hypocalcemia is well documented in clinical veterinary
      medicine. In this article, we have attempted to provide an overview of the
      established causes as well as information on more recently recognized etiologies
      such as the ionized hypocalcemia seen in cats with urethral obstruction and the
      presence of the disorder in critically ill patient populations. Hypomagnesemia
      has been identified as the most common electrolyte abnormality in canine and
      feline critically ill patients. Magnesium depletion and experience with
      supplementation appear to have most significance in diabetic ketoacidotic
      patients with the development of associated refractory hypokalemia. (N. Dhupa,
      BVM, MRCVS, unpublished observations, 1997). Although cardiac arrythmias are
      associated with hypomagnesemia in human patients, documentation of this
      association in veterinary patients is lacking. Because hypomagnesemia has been
      associated with other electrolyte abnormalities in human and veterinary
      populations, the detection of hypokalemia (particularly if refractory to
      therapy), hyponatremia, hypophosphatemia, or hypocalcemia should indicate the
      possibility of coexisting hypomagnesemia.

PMID- 9597717
TI  - Fluid therapy in acute and chronic renal failure.
AB  - Fluid therapy is one of the mainstays of treatment for renal failure, and
      rehydration is the primary goal. In those patients with ARF or "acute on chronic"
      decompensated CRF, induction of a diuresis to facilitate renal excretory function
      is important. Measurement of urine production in these patients helps guide fluid
      and electrolyte therapy. In oliguric renal failure, retention of water and
      electrolytes is likely, whereas in nonoliguric ARF as well as CRF, loss of water
      and electrolytes is the primary concern.

PMID- 9597718
TI  - Fluid therapy in shock.
AB  - The goal of treatment for all types of shock is the improvement of tissue
      perfusion and oxygenation. The mainstay of therapy for hypovolemic and septic
      shock is the expansion of the intravascular volume by fluid administration,
      including crystalloids, colloids, and blood products. Frequent physical
      examinations and monitoring enable the clinician to determine the adequacy of
      tissue oxygenation and thus the success of the fluid therapy.

PMID- 9597719
TI  - Practical approach to acid-base disorders.
AB  - Acid-base balance is a general term for the way in which the body maintains a
      relatively constant pH despite continuous production of metabolic end products
      and is fundamental to physiologic homeostasis. Disease states of animals lead to
      irregularities of body fluid, electrolyte, and acid-base balance. With the advent
      of less expensive, accurate, as well as portable blood gas and electrolyte
      analyzers, acid-base assessment has become a standard of care in veterinary
      medicine. It is important that the veterinary practitioner understand acid-base
      pathophysiology to assure successful treatment of these disease states. The
      purpose of this article is to provide a simple and concise description of
      traditional and modern acid-base data interpretation and assist the practitioner
      with application of these methods.

PMID- 9597720
TI  - Fluid therapy in the cardiac patient.
AB  - Correcting fluid deficits and preventing fluid overload in patients with cardiac
      disease can be challenging. The purpose of the fluid therapy, the projected
      duration of the therapy, and the type of heart disease affecting the patient play
      important roles in the decision-making process. In addition, the distinction
      between patients who are not symptomatic (NYHA Class I) and those who are
      symptomatic (NYHA Classes II to IV) for their cardiac disease should be made
      early in fluid therapy planning.

PMID- 9597721
TI  - The principles and practical application of enteral nutrition.
AB  - The enteral route is the preferred method of nutritional support in patients with
      functional gastrointestinal tracts. Many techniques for obtaining enteral access
      are available, and the decision regarding which one to use depends on several
      issues, including the functional integrity of each part of the gastrointestinal
      tract, the duration of anticipated nutritional support, and the risk of
      aspiration and gastroesophageal reflux. Nasoesophageal tubes are useful for short
      term supplementation; however, patients needing nutritional support for longer
      than 2 weeks may be better served with a more permanent tube. Blenderized pet
      food diets are recommended for nutritional support because these diets do not
      need to be supplemented with protein or micronutrients. Commercial human enteral
      formulas provide a useful alternative for patients with specific nutrient
      requirements or for feeding via nasoesophageal or jejunostomy tubes.

PMID- 9597722
TI  - Fluid therapy in the hypoproteinemic patient.
AB  - Hypoproteinemia can result in many adverse consequences, including hypovolemia
      and the formation of edema. An understanding of the normal forces governing
      plasma will help the clinician tailor appropriate fluid therapy in these
      patients. Various fluids that can be used including crystalloids, colloids, and
      blood products will be discussed.

PMID- 9597723
TI  - The role of flavoring substances in food allergy and intolerance.

PMID- 9597724
TI  - The use of amino acid sequence alignments to assess potential allergenicity of
      proteins used in genetically modified foods.

PMID- 9597725
TI  - Sequence databases for assessing the potential allergenicity of proteins used in
      transgenic foods.

PMID- 9597726
TI  - Design of emulsification peptides.

PMID- 9597727
TI  - X-ray diffraction of food polysaccharides.
AB  - The morphologies of food polysaccharides described in this chapter illustrate the
      power of x-ray fiber diffraction in conjunction with computer modeling and
      sophisticated refinement techniques. On the other hand, the lack of information
      on structures such as xanthan reflects the inadequacy of the experimental
      techniques used to date. But the demands from academic and industrial sectors to
      investigate the molecular interactions in multicomponent systems, including
      protein-protein, protein-polysaccharide, polysaccharide-polysaccharide, and other
      complexes, are high and growing, because they have important food applications.
      These complexes are structurally more difficult than those solved in the past 40
      years and it is improbable that any chosen system will be amenable for
      crystallographic investigation, crystals or fibers. Modern research facilities
      that include two-dimensional area detectors, millisecond exposures with
      synchrotron x-ray radiation, interactive computer graphics, sophisticated
      molecular dynamics calculations, unbelievably fast and inexpensive computers, and
      our own intellectual abilities are indispensable tools for the future of
      structural science in general and food polysaccharides in particular.

PMID- 9597728
TI  - Cellular signal transduction of sweetener-induced taste.

PMID- 9597729
TI  - Antioxidant activity of the Labiatae.

PMID- 9597730
TI  - In vitro and in vivo mineralization of Nafion membrane used for implantable
      glucose sensors.
AB  - The effects of the biological environment on the perfluorosulfonated ionomer
      Nafion membrane were investigated. Nafion membranes thermally annealed at 120
      degrees C and kept in culture medium or implanted subcutaneously in rats showed
      extensive cracking after 4 weeks. In membranes annealed at 150 degrees C,
      cracking was reduced, but not eliminated. Deposits of calcium phosphates in the
      membrane were identified. These deposits appeared to be responsible for the
      cracking of the membranes, but the precise mechanism was unclear. The
      permeability to glucose of Nafion membranes annealed at 120 degrees C increased
      at 1 week and then decreased during the 3 following weeks. However, the cracking,
      protein adhesion, and mineralization of the membranes made the results difficult
      to interpret. This study revealed that mineralization of Nafion occurs in the
      biological environment, resulting in cracking and changes in permeability.
      Modifications to prevent the mineralization of Nafion are necessary to make it
      suitable for use in the implantable glucose sensor.

PMID- 9597731
TI  - A piezoelectric quartz crystal sensor for the determination of coagulation time
      in plasma and whole blood.
AB  - A Peizoelectric Quartz Crystal (PQC) system possessing an adequate sensitivity to
      a slight viscosity change is employed to monitor the blood coagulation. In the
      case of an anticoagulated plasma specimen, prothrombin time (PT) was determined
      by the PQC sensor on the basis of the introduction of tissue thromboplastin (TF)
      and calcium ion. Discussing the PQC data statistically, we found that at 90% of
      the total frequency shift (delta f) the best linear relationship in a double
      logarithmic plot of PT versus TF concentration in the range of 5.466-22.311
      unit/ml is shown. The PQC result was compared with commercial optical
      coagulometry and showed a good linear correlation (ca. 0.98). The clotting and
      recalcification of whole blood were also studied by the PQC system. The testing
      time for one measurement could be completed within 20 min. and had a good
      agreement with that obtained conventionally.

PMID- 9597732
TI  - Engineering sensitive acetylcholinesterase for detection of organophosphate and
      carbamate insecticides.
AB  - High quantities of various acetylcholinesterases can now be produced following in
      vitro expression and it is possible to use them as biosensors to detect
      organophosphates and carbamates insecticides. In order to check the
      potentialities of acetylcholinesterase from various sources, we have studied
      enzyme from bovine erythrocyte, Electrophorus electricus, Drosophila
      melanogaster, Torpedo californica and Caenorhabditis elegans. It appears that
      insect acetylcholinesterase is more susceptible to a broad range of
      organophosphates and carbamates insecticides than the other tested enzymes. D.
      melanogaster is 8-fold more sensitive than E. electricus enzyme and this
      sensitivity has been increased to 12-fold by introducing a mutation at position
      408.

PMID- 9597733
TI  - Immobilisation of multilayer bioreceptor assemblies on solid substrates.
AB  - Multilayer assemblies were prepared by alternating adsorption of monolayers of
      monoclonal antibody against horse radish peroxidase (anti-HRP) and dextran
      sulfate (DS) on solid supports at acid pH. After crosslinking with
      glutaraldehyde, DS was washed out of the film with buffered physiological saline,
      while the antibody remained immobilised on the support. Assembly was monitored in
      situ on germanium supports by infrared multi-internal reflection spectroscopy.
      The binding capacity of the immobilised antibodies for HRP was measured by ELISA
      and by optical waveguide light mode spectroscopy. The activity of an immobilised
      anti-HRP bilayer was approximately twice that of a monolayer prepared by simple
      physiosorption. An addition of further anti-HRP layers could increase the
      activity only up to 2.5 of the monolayer activity independently of a number of
      layers in the assembly. The non-specific adsorption of proteins from human blood
      plasma was three times lower on the immobilised anti-HRP multilayer film than on
      the surface covered only with a physiosorbed anti-HRP monolayer.

PMID- 9597734
TI  - Amperometric immunosensor for lactate dehydrogenase LD-1.
AB  - An amperometric immunosensor for the detection of the lactate dehydrogenase
      isoenzyme LD-1 has been developed. Polyclonal antibodies for LD-1 have been
      covalently immobilised onto a preactivated Immunodyne ABC membrane, reacted with
      standard LD-1 solutions and placed onto a platinum working electrode polarised at
      +600 mV vs. Ag/AgCl. Lactate dehydrogenase activity has been measured by
      detection of the oxidation of NADH at the electrode surface. A calibration curve
      for LDH in the 0.005-0.12 U range has been obtained with a repeatability of 3%
      and a reproducibility of 10%. The probe exhibited good selectivity (response of
      LD-2 was 18% of LD-1) which was further improved using thermal treatment of the
      membranes. Measurement of LD-1 content in human control serum with the developed
      procedure gave a LD-1 concentration in the reported assigned range.

PMID- 9597735
TI  - A multisensor array for visualizing continuous state transitions in
      biopharmaceutical processes using principal component analysis.
AB  - An array of sensors with varying sensitivities, a so-called multisensor array,
      has been used for monitoring the growth and production states of
      biopharmaceutical processes. The sensor array produced continuous and
      characteristic response patterns from the processes due to the differences of the
      sensors. By analysing these patterns with the multivariate method principal
      component analysis, the state as well as the change of state of the bioprocesses
      could be visualized. The sensors used in the array were well-known semiconductor
      and optical gas sensors and the array was connected in an on-line set-up to the
      bioreactor's headspace effluent. The sensor array was applied to the monitoring
      of two recombinant bioprocesses, the production of human growth hormone in
      Escherichia coli and human factor VIII in Chinese ovary hamster cells. The sensor
      array could clearly visualize the characteristic transitions during the main
      growth or production phases of these two bioprocesses.

PMID- 9597736
TI  - Catheter-type sensor for potentiometric monitoring of oxygen, pH and carbon
      dioxide.
AB  - The fabrication and analytical performance of a catheter-type electrode suitable
      for potentiometric monitoring of PO2, pH and PCO2 in flowing blood is described.
      The catheter electrode is based on impregnating a single segment of dual-lumen
      gas permeable silicone rubber tubing with the proton ionophore tridodecylamine to
      impart H+ permselectivity to both inner and outer walls of the tubing. One lumen
      is filled with an unbuffered bicarbonate solution and the other lumen is filled
      with a strong buffer. By inserting Ag/AgCl reference electrode wires in each
      lumen and a cobalt electrode in the buffered lumen, simultaneous potentiometric
      detection of PO2, pH and PCO2 is achieved. The response of cobalt electrode to
      PO2 arises from a steady-state mixed potential owing to slow oxidation of cobalt
      and simultaneous reduction of oxygen on the surface of the cobalt electrode. The
      response towards PCO2 is completely analogous to the response mechanism of a
      conventional Severinghaus PCO2 sensor (i.e., change in pH of the bicarbonate
      solution). Continuous measurements of PO2, pH and PCO2 during 4-5 h blood pump
      studies using the catheter electrodes correlate well with conventional bench-top
      blood gas analyzer (PO2: r2 = 0.992; pH: r2 = 0.940; PCO2: r2 = 0.993.

PMID- 9597737
TI  - Thermal analysis of cryoprotective solutions for red blood cells.
AB  - A differential scanning calorimeter was used to study the thermal behavior of
      glycerol-water solutions (binary system) and the more complex glycerol-based
      cryoprotective solutions that are used clinically in order to examine the
      cryoprotective role of glycerol in preserving frozen red blood cells. The melting
      and glass transition temperatures for the clinically used cryoprotective
      solutions were as expected, based on the nonequilibriumphase diagram for
      cryoprotective solutions incorporating isotonic phosphate-buffered saline. Two
      zones were identified in which solidification occurred without the formation of
      ice crystals: a glassy state that is crystallographically amorphous was found for
      glycerol concentrations between 40 and 55% in the binary system and between 45
      and 60% in the complex system; a glassy state in the complete absence of ice was
      found at glycerol concentrations greater than 55% for the binary system or 60%
      for the complex system. In clinical practice, cryoprotectants are used at initial
      concentrations lower than those at which these two glassy states occur but there
      is an increase in the effective glycerol concentration inside and outside the
      cells as ice forms during the freezing process.

PMID- 9597739
TI  - Effect of cryopreservation on chemotaxis of lymphocytes.
AB  - Cryopreservation of cells appears to be a potential method of comparing
      chemotaxis of lymphocytes collected from different anatomical sites at one time
      in a single assay. Migration of cryopreserved lymphocytes from swine in the
      absence (spontaneous migration) or presence of N-formyl-methionyl-leucyl
      phenylalanine (fMLP, induced migration) was compared to that of fresh
      lymphocytes, originating from inguinal (ILN) and mesenteric (MLN) lymph nodes,
      respectively, using a 48-well microchemotaxis chamber. Cryopreservation did not
      affect the optimal concentration of fMLP for maximal induced migration and did
      not impair the chemoattractant activity of fMLP as shown by checkerboard assay.
      However, cryopreservation reduced the extent of fMLP-induced migration by
      affecting the spontaneous motility of cells, an effect which was greater for MLN
      than for ILN cells. This reduction was not related to a loss of cell subset and
      is in keeping with the view that spontaneous and induced migration involve
      distinct mechanisms. Thus cryopreservation may be of general use to study the
      migration of lymphocytes by reducing the differences in spontaneous migration of
      lymphocytes from different sites.

PMID- 9597738
TI  - A comparative study of cryogenic lesions in organ-cultured human skin and in
      reconstituted human skin equivalent.
AB  - Cryosurgery is a technique that is widely used in the treatment of cutaneous
      tumors. However, there are still features of healing in cryosurgery wounds that
      are incompletely understood and necessitate further study. In the present paper,
      we describe two in vitro models that were developed to study the initial stages
      of development of the cryolesion: reconstituted human skin and organ-cultured
      human skin. Cryolesions were generated in both models by applying a 2-mm-diameter
      cryoprobe at -196 degrees C for 35 s. Histological features were analyzed at days
      0, 3, 5, and 14 following cryotreatment and showed epidermal detachment and
      keratinocyte necrosis very close to the findings reported in vivo. Results were
      similar in the two models. Gross alteration of the dermal architecture was
      noticed beneath the cryolesion, particularly in the reconstituted skin model.
      Cell proliferation was investigated at days 0, 3, and 5 by [3H]thymidine
      incorporation and Ki-67 antigen immunolabeling. In the case of organ-cultured
      skin, a significant increase in keratinocyte and fibroblast proliferation was
      observed at day 3, compared to the controls. At day 5, a return to the basic
      level was noticed. This was not observed in the reconstituted skin model at
      either day 3 or day 5. These data led us to propose that organ-cultured skin may
      be a useful model for evaluating the response of human skin to freezing;
      reconstituted skin was not adequate for this purpose.

PMID- 9597740
TI  - Effects of centrifugation and lipid removal on the cryopreservation of in vitro
      produced bovine embryos at the eight-cell stage.
AB  - The effects of intracellular lipid polarization and lipid removal treatments on
      the postthawed in vitro development of frozen bovine embryos at the 8-cell stage
      were studied. As the first step, bovine presumptive zygotes were centrifuged at
      16,000 g for 20 min for the cytoplasmic lipid polarization and their lipid layers
      were removed by micromanipulation in order to examine the influence of these
      treatments on the developmental capacity of bovine zygotes. As the second step,
      bovine embryos developed to the 8-cell stage following centrifugation treatment
      at various forces (8000, 12,000, and 16,000 g) or lipid removal treatment at the
      1-cell stage were frozen in 1.8 M ethylene glycol + 0.05 M trehalose supplemented
      with 5% polyvinylpyrrolidone in a one-step procedure. There were no significant
      differences among the control (nontreatment), lipid-polarized, and lipid-removed
      groups with respect to the developmental capacity of fresh nonfrozen zygotes
      (experiment 1). The rates of survival and development to the blastocyst of frozen
      thawed 8-cell embryos increased slightly with increasing force of centrifugation
      (experiment 2). The rate of development into blastocysts of the frozen-thawed 8
      cell embryos was significantly higher in the groups that underwent centrifugation
      (at 16,000 g for 20 min; P < 0.05) or lipid removal (P < 0.01) treatments than
      the control (intact) group. However, there were no significant differences among
      the groups with respect to the rate of development to the expanded/hatched
      blastocyst stage. In addition, the mean cell numbers of embryos developed into
      blastocysts (day 8) derived from frozen-thawed 8-cell embryos tended to be low in
      the centrifugation and lipid removal groups compared to the controls (experiment
      3). These results suggest that although the centrifugation with or without lipid
      removal treatments has no detrimental effects on the developmental capacity of
      bovine zygotes, the freezing tolerance of bovine 8-cell embryos was not improved
      by these treatments.

PMID- 9597741
TI  - Post pupariation cold storage of three species of flies: increasing chilling
      tolerance by acclimation and recurrent recovery periods.
AB  - Three species of flies were examined for chilling tolerance from the end of the
      pupariation to the onset of adult eclosion for the purpose of determining
      applicability for cold storage. For the housefly, Musca domestica (Diptera,
      Muscidae), survival to eclosion was affected by developmental stage/age, length
      of storage, and storage temperature. Houseflies that were closest to having
      experienced pupariation or the onset of eclosion were the least cold tolerant.
      For flies stored at 7 or 10 degrees C, age groups placed directly into storage at
      36-72 and 36-48 h postpupariation, respectively, had significantly higher
      poststorage eclosion than younger or older age groups. Death was observed after
      only 2 or 3 days with the chilling intolerant groups while mid-aged groups
      survived 10-12 days under cold storage conditions. Damage could be reduced by
      giving the mid-aged groups chilled at 7 or 10 degrees C recurrent 2- or 3-h
      recovery periods every 4 days at 28 degrees C. Examination of O2 consumption
      throughout the housefly pupal and pharate adult stages showed that the most
      chilling tolerant groups also had the lowest metabolic activity. Combining a
      prestorage 17-h slow cooling acclimation interval with the recurrent recovery
      periods increased eclosion of adults 20% for the 12- to 24-h group after 21 days
      storage at 7 degrees C. Two blowfly species, Lucilia cuprina and Lucilia sericata
      (Diptera, Calliphoridae), survived 10 degrees C storage best when given a weekly
      4-h recovery period. Survival at 90 days poststorage was nearly 50% for L.
      cuprina and 80% for L. sericata. Increasing survival under subambient
      temperatures for all three species appears to relate to whether there is a stage
      of development which allows cold-induced lowering of metabolism that results in a
      dormant status best characterized as hibernal quiescence. This study indicates
      that periodic warming during cold storage increases survival by allowing a
      chilling intolerant stage to develop to a more tolerant stage and/or by
      eliminating accumulated toxic metabolites.

PMID- 9597743
TI  - Glutathione movements during cold preservation of rat hepatocytes.
AB  - In this study we have examined the movements of glutathione (GSH) during cold
      preservation of rat hepatocytes in University of Wisconsin solution. During the
      preservation process at a low temperature (4 degrees C), with a high
      extracellular potassium concentration, an extracellular nondiffusible anion
      (lactobionate), and a Cl(-)-free medium, there is a depletion of metabolites and
      the development of a time-dependent injury. Also, there is a loss of GSH that is
      not compensated by transport or synthesis and is basically due to increased
      catabolic processes. This sensitizes the cells to different forms of oxidative
      injury, which can play a negative role during transplantation. The addition of
      GSH improves liver cell preservation but the mechanism is unclear. To elucidate
      this process we have isolated hepatocytes and preserved them under different
      conditions: with or without GSH: in the presence of DL-buthionine-[S,R]
      sulfoximine, an inhibitor of glutathione synthetase, and acivicine to inhibit the
      ectoactivity of cellular gammaglutamyl transpeptidase; or by obtaining
      hepatocytes from rats depleted of GSH by an injection of diethyl maleate. Under
      all these conditions we evaluated the GSH content of the cells during cold
      storage. We also report the time course of accumulation of [glycine-2-3H]GSH. Our
      results show that during hypothermic storage in University of Wisconsin solution,
      hepatocytes are permeable to GSH, and the mechanism involved is a rapid
      nonsaturable process, with linear dependence of the extracellular GSH
      concentration. This finding may have valuable applications in the improvement of
      the delivery of compounds to cells.

PMID- 9597742
TI  - Metabolic effects of citrate in liver during cold hypoxia studied by 1H NMR
      spectroscopy.
AB  - We propose the use of 1H nuclear magnetic resonance (NMR) spectroscopy to
      investigate metabolite fluxes in the mammalian liver during cold hypoxia. Rat
      livers were flushed with one of four different preservation solutions and stored
      on ice in the same solution. The preservation solutions were: Marshall's
      hypertonic citrate (HC); carnosine modified HC (HC-C); modified University of
      Wisconsin (mod UW); and Bretschneider's histidine--typtophan--ketoglutarate
      (HTK). Liver biopsies were taken before and at 1, 2.5. 4, 24, and 48 h after
      storage, and freeze-clamped. The liver was extracted with perchloric acid and
      analyzed by 1H NMR spectroscopy. Components of the individual preservation
      solutions, such as citrate, histidine, mannitol, and raffinose, were detected in
      the extracts. Lactate was increased over the first 4 h in all stored livers, but
      only continued to increase in those stored in HC-C and HTK, reaching
      significantly high levels of 15 and 14 mumol/g, respectively, by 48 h storage (P
      < 0.05 and P < 0.01, respectively). Levels of succinate and fumarate in all
      livers were generally unchanged in the first 0-4 h of storage. However, after 4 h
      of storage, succinate levels rose in the HC and HC-C livers, while remaining
      unchanged in mod UW and HTK livers. The presence of citrate in the preservation
      solutions appeared to enhance the late hepatic synthesis of succinate. Fumarate
      levels were significantly decreased by 48 h of cold storage, indicating continued
      fumarate consumption at low temperatures. Despite cold hypoxic conditions, some
      carbon-substrate cycling appears to continue in mammalian liver via pathways
      other than glycolysis, and citrate from the preservation solution appears to
      influence this.

PMID- 9597744
TI  - Vitrification of immature porcine oocytes: effects of lipid droplets,
      temperature, cytoskeleton, and addition and removal of cryoprotectant.
AB  - Three experiments were conducted to investigate the effects of single-step and
      stepwise exposure to and removal of cryoprotectant, of temperature, and of a
      cytoskeletal relaxant on the development of germinal vesicle porcine oocytes to
      the M-II stage. In experiment I, noncooled cumulus-oocyte complexes (COCs) were
      treated using single-step/stepwise exposure to ethylene glycol (EG) and removal
      at 23 or 42 degrees C. Stepwise exposure to EG and dilution at 42 degrees C were
      found to have a positive effect on the COC developmental rate. In experiment II,
      also without cooling, COCs were treated with Cytochalasin B at 42 degrees C using
      single-step and stepwise protocols of exposure to and removal of EG. No effects
      of Cytochalasin B were noticed on the COCs pretreated for vitrification but not
      cooled. In experiment III, COCs were divided into two treatment groups and one
      control group. Group 1 COCs were vitrified by stepwise exposure to EG at 42
      degrees C and direct plunging into liquid nitrogen. Warming was carried out by 5
      s immersion in a water bath at 50 degrees C, and the cryoprotectant was removed
      by exposure to a graded series of sucrose solutions at 42 degrees C. Group 2 COCs
      were vitrified using the same procedure but following pretreatment with
      Cytochalasin B. Group 3 COCs were control (untreated) oocytes. After rewarming
      and passage through the sucrose series, the experimental COCs were cultured for
      48 h. The results of cultivation (progression to MII stage) suggest that the
      gradual saturation/removal of cryoprotectant, elevated temperature, and
      pretreatment with cytoskeletal inhibitor Cytochalasin B have a positive effect on
      vitrification of GV-porcine oocytes.

PMID- 9597745
TI  - The concept of nation-state in Italian elementary school children: spontaneous
      concepts and effects of teaching.
AB  - Two experiments were conducted. In Experiment 1, the definitions given by
      kindergarteners, third graders, and sixth graders (N = 60) for several political
      terms were searched for a characteristic-to-defining-shift (Keil, 1989). The
      children were presented with seven words: kingdom, king, border, tax, soldier,
      capital city, and policeman and were asked (a) if and where they had ever heard
      each of them and, if they had, (b) to explain their meanings. Kindergarten
      children did not know most of the terms or defined them mainly by means of
      characteristic but nondefining features. The third graders appeared to represent
      the state only in physical terms. Soldiers and policemen were described as
      employees but not as public servants. In Experiment 2, the extent to which
      children's misconceptions can be changed through explicit instruction was
      examined. A curriculum lasting about 16 hr was implemented with a group of fourth
      graders (N = 30). On pretest, most of the children depicted the state in the same
      ways as the third graders had in Experiment 1. After the curriculum
      implementation, nearly all of the children showed a political conception of the
      state, describing it not only in terms of a territory in which a population is
      settled but also in terms of government.

PMID- 9597746
TI  - Parafoveal identification asymmetry: interactive effects of shape and color.
AB  - If two adjacent letters project to the parafoveal region of the retina, both
      accuracy and discriminability measures have revealed that a letter flanked to its
      foveal side is identified more accurately than a letter the same distance from
      the fovea that is flanked to its peripheral side. This parafoveal identification
      asymmetry is greater if the letters are dissimilar in shape than if they are
      similar. Color and brightness were introduced as variables in the present
      experiments. The identification asymmetry was greatest for dissimilar letters in
      different (complementary) colors. Although those colors differed also in
      brightness, two letters that were achromatic but merely different in brightness
      did not produce an asymmetry interaction with shape. Interletter separation was
      varied between .15 and 1.95 deg, and the pattern of results just described
      persisted across both distances. The synergistic interaction of shape relation
      and color relation in determining the amount of identification asymmetry suggests
      that color and shape affect perceptual processing at the same level.

PMID- 9597747
TI  - Emotional dissonance in organizations: antecedents, consequences, and moderators.
AB  - Emotional dissonance, or person-role conflict originating from the conflict
      between expressed and experienced emotions, was examined. The study was based on
      a reconceptualization of the emotional labor construct, with dissonance as a
      facet rather than a consequence of emotional labor. The effects of emotional
      dissonance on organizational criteria were isolated, thereby explaining some of
      the conflicting results of earlier studies. Empirically, job autonomy and
      negative affectivity as antecedents of emotional dissonance, and emotional
      exhaustion and job satisfaction as consequences of emotional dissonance, were
      explored. Self-monitoring and social support were tested as moderators of the
      emotional dissonance-job satisfaction relationship. Significant relationships
      with job autonomy, emotional exhaustion, and job satisfaction were found. Social
      support significantly moderated the emotional dissonance-job satisfaction
      relationship.

PMID- 9597748
TI  - Pyruvate carboxylase.
AB  - Pyruvate carboxylase [EC 6.4.1.1] is a member of the family of biotin-dependent
      carboxylases and is found widely among eukaryotic tissues and in many prokaryotic
      species. It catalyses the ATP-dependent carboxylation of pyruvate to form
      oxaloacetate which may be utilised in the synthesis of glucose, fat, some amino
      acids or their derivatives and several neurotransmitters. Diabetes and
      hyperthyroidism increase the level of expression of pyruvate carboxylase in the
      long term, while its activity in the short term is controlled by the
      intramitochondrial concentrations of acetyl-CoA and pyruvate. Many details of
      this enzyme's regulation are yet to be described in molecular terms. However,
      progress towards this goal and towards understanding the relationship of pyruvate
      carboxylase structure to its catalytic reaction mechanism, has been enormously
      enhanced recently by the cloning and sequencing of genes and cDNAs encoding the
      approximately 130 kDa subunit of this homotetramer. Defects in the expression or
      biotinylation of pyruvate carboxylase in humans almost invariably results in
      early death or at best a severely debilitating psychomotor retardation, clearly
      reflecting the vital role it plays in intermediary metabolism in many tissues
      including the brain.

PMID- 9597749
TI  - The uncoupling protein, thermogenin.
AB  - The uncoupling protein (UCP) or thermogenin is a 33 kDa inner-membrane
      mitochondrial protein exclusive to brown adipocytes in mammals that functions as
      a proton transporter, allowing the dissipation as heat of the proton gradient
      generated by the respiratory chain and thereby uncoupling oxidative
      phosphorylation. Thermogenesis (heat production) in brown adipose tissue, which
      is activated in response to cold exposure or chronic overeating, depends largely
      on UCP activity. Norepinephrine, released from sympathetic terminals and acting
      via beta-adrenoceptors and cAMP, is the main positive regulator of both UCP
      synthesis and activity. Brown fat thermogenesis plays a critical role in
      thermoregulation and in overall energy balance, at least in rodents. Manipulation
      of thermogenesis, whether through UCP or through analogous uncoupling proteins,
      could be an effective strategy against obesity.

PMID- 9597750
TI  - Structure, function and physiological role of glycine N-methyltransferase.
AB  - Glycine N-methyltransferase (EC 2.1.1.20) catalyzes the transfer of the methyl
      group of S-adenosylmethionine (AdoMet) to glycine to form S-adenosylhomocysteine
      and sarcosine. Unlike most AdoMet-dependent methyltransferases, glycine N
      methyltransferase is a tetramer of identical subunits. Crystallography of
      recombinant rat glycine N-methyltransferase indicates that four nearly spherical
      subunits are arranged to form a flat, square tetramer with a large hole in the
      centre. The enzyme occurs abundantly in the livers of rat, rabbit and mouse.
      Glycine N-methyltransferases from rat, rabbit, human and pig livers are shown to
      have similar amino acid sequences and, with the enzymes from rat and rabbit
      livers, it is demonstrated that the N-terminal valine is acetylated. Glycine N
      methyltransferases from livers exhibit sigmoidal rate behaviour with respect to
      AdoMet and hyperbolic behaviour with respect to glycine at all pH tested.
      However, recombinant rat glycine N-methyltransferase which lacks the N-terminal
      acetyl group shows no cooperativity toward AdoMet at neutral pH, suggesting that
      elimination of the positive charge at the N-terminus is required for cooperative
      behaviour. Glycine N-methyltransferase binds 5
      methyltetrahydropteroylpentaglutamate tightly, resulting in inhibition of the
      catalytic activity. The nature of these unique functional features is discussed
      in the light of the three-dimensional structure of the enzyme. The tissue and
      subcellular localization of the enzyme and its possible role in methionine
      metabolism are reviewed.

PMID- 9597751
TI  - Coupling gene expression to cAMP signalling: role of CREB and CREM.
AB  - Several endocrine and neuronal functions are governed by the cAMP-dependent
      pathway. Transcriptional regulation upon stimulation of this pathway is mediated
      by a family of cAMP-responsive nuclear factors. This family consists of a large
      number of members, which may act as activators or repressors. These factors
      contain the basic domain/leucine zipper motifs and bind as dimers to cAMP
      response elements (CRE). CRE-binding protein (CREBs) function is modulated by
      phosphorylation by several kinases. Direct activation of gene expression by CREB
      requires phosphorylation by the cAMP-dependent PKA to serine 133. Among the
      repressors, ICER (Inducible cAMP Early Repressor) deserves special mention. ICER
      is generated from an alternative CREM promoter and is the only inducible CRE
      binding protein. ICER negatively autoregulates the alternative promoter,
      generating a feedback loop. ICER expression is tissue specific and
      developmentally regulated. The kinetics of ICER expression are characteristic of
      an early response gene. CREM plays a key physiological and developmental role
      within the hypothalamic-pituitary-gonadal axis. The transcriptional activator
      CREM is highly expressed in postmeiotic cells. The role of CREM in spermiogenesis
      was addressed using CREM knock-out mice. Spermatogenesis stops at the first step
      of spermiogenesis in the mutants and there is a significant increase in apoptotic
      germ cells. This phenotype is reminiscent of cases of human infertility. ICER is
      regulated in a circadian manner in the pineal gland, the site of the hormone
      melatonin production. This night-day oscillation is driven by the endogenous
      clock (located in the suprachiasmatic nucleus). The synthesis of melatonin is
      regulated by a rate-limiting enzyme, serotonin N-acetyltransferase (NAT).
      Analysis of the CREM-null mice and of the promoter of the NAT gene revealed that
      ICER controls the amplitude and rhythmicity of NAT, and thus the oscillation in
      the hormonal synthesis of melatonin.

PMID- 9597752
TI  - Forced expression of hic-5, a senescence-related gene, potentiates a
      differentiation process of RCT-1 cells induced by retinoic acid.
AB  - The hic-5 gene encodes the novel LIM protein which has been implicated in
      cellular senescence and differentiation processes. Previous studies of rat
      calvarial cells stimulated to differentiate by addition of retinoic acid (R.A.)
      showed a four-fold increase in hic-5 expression which preceded an increase in the
      expression of the differentiation markers, alkaline phosphatase and alpha (I) pro
      collagen mRNA. These data suggest involvement of hic-5 in osteoblast
      differentiation. This hypothesis was further examined using rat calvarial RCT-1
      cells containing expression vectors of hic-5. The over-expressing clones showed a
      decrease in proliferation and displayed the differentiation-related phenotypes
      such as increased basal levels of alpha (I) collagen mRNA expression and high
      inducibility by R.A. of alkaline phosphatase activity. Conversely, introduction
      of hic-5 anti-sense vector leads to the inhibition of alpha (I) collagen mRNA
      following induction by R.A. These results suggest that hic-5 is one of the
      regulatory molecules involved in the R.A. induced differentiation process of RCT
      1 cells.

PMID- 9597753
TI  - Growth factors increase pericellular proteoglycans independently of their
      mitogenic effects on A10 rat vascular smooth muscle cells.
AB  - Proliferation of vascular smooth muscle cells with the accumulation of
      proteoglycans in the extracellular matrix is one of the significant changes found
      in atherosclerotic lesions. In order to clarify the relationship between
      pericellular proteoglycan and cell growth, we established a simple method for
      quantitatively estimating the amount of pericellular proteoglycans and
      investigated the effects of various growth factors on the synthesis of
      pericellular proteoglycans by cultured A10 rat smooth muscle cells. Analysis of
      trypsin accessible [35SO4]-labeled material in the pericellular area of the A10
      cell culture by Q-sepharose anion-exchange chromatography showed two peaks. One
      peak, eluted at 0.55 M NaCl, disappeared after treatment with 2 mU/ml of
      heparitinase, indicating that heparan sulfates (HS) were present. The other peak,
      which eluted at 0.65 M NaCl, disappeared with 20 mU/ml of chondroitinase ABC,
      indicating the presence of chondroitin sulfates and dermatan sulfates (CS/DS). We
      estimated the effects of several growth factors on the synthesis of the
      pericellular proteoglycans by measuring heparitinase- and chondroitinase-ABC
      sensitive radioactivities. Although PDGF-AB significantly stimulated cell
      proliferation and the synthesis of pericellular CS/DS, its dose-dependent effect
      on the cell growth did not coincide with that on the proteoglycan synthesis. IGF
      I (1 nM) increased pericellular CS/DS but not the cell number, while basic FGF (1
      nM) and EGF (1 nM) increased the cell number but not pericellular CS/DS. All the
      growth factors we examined had no effect on the synthesis of pericellular HS.
      These results indicate that growth factors increase pericellular proteoglycans
      independently of their mitogenic effects.

PMID- 9597754
TI  - Cellular uptake of stearic, oleic, linoleic, and linolenic acid and their effects
      on synthesis and secretion of lipids in Hep-G2 cells.
AB  - The present study was undertaken to examine the cellular uptake of stearic
      (18:0), oleic (18:1), linoleic (18:2), and linolenic acid (18:3), and their
      effects on synthesis and secretion of lipids in Hep-G2 cells. The cells were
      grown for 6 days in Dulbecco's modified Eagle's medium (DMEM) supplemented with
      10% fetal bovine serum. On day 7, cells were incubated in a serum-free DMEM
      containing 0.25-1.0 mM of 18:0, 18:1, 18:2 or 18:3. The cellular uptake of these
      fatty acids was almost linear during the 4 hr incubation period, and no
      significant differences were noted among the fatty acids tested, regardless of
      their degree of unsaturation. The treatment of cells with 1.0 mM of these fatty
      acids stimulated triglyceride (TG) synthesis nearly ten-fold and phospholipid
      (PL) synthesis approx, two-fold compared with those of the control. The
      lipoprotein-TG secretion also increased and was the highest with 18:1 followed in
      descending order by 18:2, 18:3, and 18:0. The fatty acid treatment of cells also
      significantly increased the incorporation of 14C-acetate into the cellular and
      lipoprotein cholesterol compared with that of the control (p < 0.05). In
      addition, notable changes occurred in the fatty acid composition of cellular and
      medium lipids, which were enriched with the particular fatty acid present in the
      incubation medium. The findings that 18:0, 18:1, 18:2, and 18:3 were taken up by
      Hep-G2 cells at almost identical rates demonstrate that differences in the
      cellular synthesis of lipids and their secretion are attributable to the
      metabolic specificity of those fatty acids, rather than variable rates of their
      uptake.

PMID- 9597755
TI  - The glycosylation sites and structural characteristics of oligosaccharides on
      recombinant human thrombomodulin.
AB  - Thrombomodulin (TM) is an anticoagulant glycoprotein on the surface of
      endothelial cell that directly inhibits the procoagulant activities of thrombin,
      and the TM-thrombin complex accelerates thrombin-catalyzed activation of protein
      C. Soluble TM in urine has no glycosaminoglycan (GAG) chain which accelerates the
      anticoagulant activities. Therefore, we expressed recombinant GAG-modified
      urinary thrombomodulin (GAG-UTM) in C127 cells. The glycosylation sites were
      determined by amino acid sequence analysis of peptides digested with trypsin
      after S-carboxymethylation. The structures of N-linked oligosaccharides were
      estimated by two-dimensional sugar mapping of pyridylaminated oligosaccharides
      that were treated with exoglycosidase. The disaccharide composition analysis of
      the GAG chain was performed by HPLC using digestion with chondroitinase ABC, ACII
      and B. Consequently, it was revealed that the N-linked oligosaccharides were
      assigned to Asn29, Asn98, Asn364, Asn391; those structures were estimated
      biantennary, 2-6 branched triantennary and 2-4 branched triantennary complex type
      oligosaccharides that were linked by fucose at the ratio of 1.0:0.5:0.1,
      respectively. Moreover, the attachment site of the GAG chain was assigned to
      Ser472. It was then estimated that the GAG chain contained chondroitin-4-sulfate
      and dermatan sulfate, which were repeated approximately 30 times. In this paper,
      the GAG attachment site and structural characteristics of GAG-UTM, were
      confirmed. Moreover, structures of the N-linked oligosaccharides of GAG-UTM are
      described for the first time.

PMID- 9597756
TI  - Allosteric modulation of pyrophosphatase activity of rat osseous plate alkaline
      phosphatase by magnesium ions.
AB  - Pyrophosphatase activity of rat osseous plate alkaline phosphatase was studied at
      different concentrations of calcium and magnesium ions, with the aim of
      characterizing the modulation of enzyme activity by these metals. In the absence
      of metal ions, the enzyme hydrolysed pyrophosphate following "Michaelian"
      kinetics with a specific activity of 36.7 U/mg and K0.5 = 88 microM. In the
      presence of low concentrations (0.1 mM) of magnesium (or calcium) ions, the
      enzyme also exhibited "Michaelian" kinetics for the hydrolysis of pyrophosphate,
      but a significant increase in specific activity (123 U/mg) was observed, K(m)
      values remained almost unchanged. Quite different behavior occurred in the
      presence of 2 mM magnesium (or calcium) ions. In addition to low-affinity sites
      (K0.5-40 and 90 microM, for magnesium and calcium, respectively), high-affinity
      sites were also observed with K0.5 values 100-fold lower. The high-affinity sites
      observed in the presence of calcium ions represented about 10% of those observed
      for magnesium ions. This was correlated with the fact that only magnesium ions
      triggered conformational changes yielding a fully active enzyme. These results
      suggested that the enzyme could hydrolyse pyrophosphate, even at physiological
      concentrations (4 microM), since magnesium concentrations are high enough to
      trigger conformational changes increasing the enzyme activity. A model,
      suggesting the involvement of magnesium ions in the hydrolysis of pyrophosphate
      by rat osseous plate alkaline phosphatase is proposed.

PMID- 9597757
TI  - A study of prolyl endopeptidase in bovine serum and its relevance to the tissue
      enzyme.
AB  - Prolyl endopeptidase (PE) belongs to a group of enzymes that specifically
      recognise the imino acid proline. The characterisation of bovine serum PE was
      undertaken so that its relationship to its tissue counterparts could be
      considered. Using various chromatographic methods, PE was partially purified from
      bovine serum. This preparation was deemed to be enzymatically pure, based on its
      failure to hydrolyse a wide range of fluorimetric substrates. A native molecular
      mass of 69.7 kDa was estimated for the enzyme. PE was optimally active at pH 8.0
      8.5, demonstrated a preference for phosphate buffer and remained stable over a pH
      range of 5.0-9.0. A narrowly focused optimal assay temperature of 37 degrees C
      was evident. Functional reagent studies indicated that this enzyme was a serine
      protease with a cysteine residue located near or at the active site. The enzyme
      was also sensitive to heavy metal inhibition. Substrate specificity
      investigations revealed that the bioactive peptides angiotensin II, bradykinin,
      luliberin and substance P were hydrolysed by the enzyme preparation, but lower
      specificities were evident towards these peptides in comparison with the enzyme's
      tissue counterparts. Specific inhibitor studies, using a range of compounds
      previously untested against a single PE source, indicated that alpha
      ketobenzothiazole was the most effective PE inhibitor, with an IC50 value of 41
      pM. In conclusion, the results presented in this paper indicate that bovine serum
      PE shares many of the characteristics associated with its tissue counterparts,
      with the exception of its specificity towards certain bioactive peptides.

PMID- 9597758
TI  - A study of a highly specific pyroglutamyl aminopeptidase type-II from the
      membrane fraction of bovine brain.
AB  - Pyroglutamyl aminopeptidase type-II is reported to be a highly specific, membrane
      bound neuropeptidase, which has the ability to hydrolytically remove the L
      pyroglutamyl residue (pGlu) from the N-terminus of thyrotropin releasing hormone
      (TRH, pGlu-His-Pro-NH2) and closely related tripeptides or tripeptide amides. The
      primary aim of this study was to purify this enzyme from bovine brain and to
      compare its characteristics with those previously reported. Following
      solubilization from the membrane fraction by limited proteolysis with trypsin,
      the enzyme was purified approximately 3000-fold with a 24% recovery of activity.
      A native molecular mass of 214,000 Da was determined for the purified enzyme by
      gel-filtration chromatography. A pH optimum of 6.8-7.6 was observed for the
      enzyme, with rapid inactivation occurring below pH 4.0 and above pH 9.2. Optimal
      enzyme activity was observed at 45 degrees C. On the basis of its inhibition, in
      a time-dependent manner, by metal complexing agents and its subsequent
      reactivation in the presence of metal ions, the enzyme was identified as a
      metallopeptidase. Substrate specificity studies revealed that, with the exception
      of pGlu-Phe-Pro-NH2, pGlu-7-amino-4-methyl-coumarin and pGlu-beta-naphthylamide,
      the purified enzyme removes N-terminal pGlu from only tri- and tetrapeptides with
      a histidine residue in the penultimate position. A number of N-terminal
      pyroglutamyl peptides of varying length were shown to competitively inhibit the
      enzyme. Of these, luteinizing hormone releasing hormone (LHRH) and LHRH 1-5,
      although not substrates for the enzyme, were found to be potent inhibitors, with
      Ki values of 8 and 11 microM, respectively. The study shows that while bovine
      brain PAPII shares many of the characteristics of PAPII from other mammalian
      tissues, its substrate specificity is not as narrow as previously reported.

PMID- 9597759
TI  - Polyamines induce malignant transformation in cultured NIH 3T3 fibroblasts.
AB  - Previous studies have demonstrated that polyamines accumulate in cancer cells and
      that overproduction of ornithine decarboxylase (ODC), which catalyzes polyamine
      synthesis, elicits the acquisition of the transformed phenotype. However, it was
      not clear whether the overexpression of ODC and the accumulation of polyamines
      are only innocent by-products of the transformation process. In this study we
      demonstrate that polyamines as such, may play a crucial role in malignant
      transformation. The system used consisted of NIH 3T3 fibroblasts transfected with
      a construct (pATMras) in which Ha-ras was under the transcriptional control of
      the mouse mammary tumor virus long terminal repeat (MMTV-LTR) promoter (MMTVras
      cells). Dexamethasone, which activates the promoter, triggered phenotypic
      transformation. This was accompanied by an increase in ODC activity and polyamine
      accumulation. Cells, thus transformed, grew in soft agar and formed typical foci.
      alpha-Difluoromethylornithine (DFMO), which blocks polyamine synthesis, inhibited
      the dexamethasone-enhanced transformation. This inhibition was reversed by
      polyamines. Polyamines caused transformation of MMTVras cells in the absence of
      dexamethasone. Under these conditions, cells became anchorage independent. This
      phenomenon is not explained by the leakiness of ras, since normal, immortalized
      NIH 3T3 fibroblasts, also grew in soft agar in the presence of polyamines. Taken
      together, these observations suggest that polyamines may stimulate malignant
      transformation of immortalized cells, in cooperation with other factors, such as
      oncogenes or genetic defects.

PMID- 9597760
TI  - Platelets from eclampsia patients have reduced membrane microviscosity and lower
      activities of the signalling enzymes.
AB  - It has been shown that platelets from patients suffering from eclampsia are
      hyporesponsive to stimulation by agonists like thrombin and ADP. Although
      platelet hyporeactivity contributes to the pathogenesis of the disease process,
      the cause for this is still not known. Platelet aggregation and secretion are
      membrane-based phenomena initiated by the processes of cell signalling. Hence, to
      understand the mechanisms underlying platelet hyporeactivity in eclampsia,
      membrane microviscosity and activities of the signalling enzymes were measured in
      human platelets stimulated with thrombin. Membrane fluidity was determined from
      the steady-state fluorescence anisotropy of diphenylhexatriene incorporated in
      cell membranes. Activities of phospholipase C and protein kinase C in stimulated
      platelets were assessed from the extents of phosphatidic acid generation and
      pleckstrin phosphorylation, respectively. Platelet membrane microviscosity in
      eclampsia (2.3 +/- 0.2 SEM, n = 5) was significantly lower (P < 0.05) than that
      in the matched gravid control subjects (3.1 +/- 0.2, n = 4). In eclampsia,
      generation of phosphatidic acid and phosphorylation of pleckstrin were decreased
      by 25% (P < 0.05, n = 3) and 35% (P < 0.05, n = 3), respectively, after 60 sec of
      platelet stimulation. It was concluded that the hyporeactive platelets obtained
      from eclampsia have more fluid membranes and diminished activities of
      phospholipase C and protein kinase C. In summary, this study shows that
      alterations in membrane fluidity and activities of the signalling enzymes
      (phospholipase C and protein kinase C) may contribute to the diminished platelet
      responsiveness observed in the eclamptic condition.

PMID- 9597763
TI  - Existence and localization of a protein in zebra finch brain with similar
      structural features as the large subunit of the splicing factor U2AF.
AB  - From brains of the adult male zebra finch, we purified a peptide that has a
      homologous sequence of the large subunit of human U2AF. U2AF is a non-small
      nuclear ribonucleoprotein (snRNP) splicing factor required for pre-spliceosome
      assembly. U2AF consists of a large and a small subunit, whereas only a large
      subunit is required for in vitro splicing. To show that U2AF large-subunit-like
      protein exists in the brain of zebra finches, we conducted immunoblot analysis on
      brain extract, using antiserum against an isolated peptide with primary
      structures similar to the U2AF large subunit (ppU2AFls). The immunoblot analysis
      showed that a protein with a molecular weight of about 60 kd reacted with the
      anti-ppU2AFls-antibody to a putative peptide of the U2AF large subunit. To
      examine the localization of this protein in the brain, we also conducted
      immunohistochemical analysis with the anti-peptide. An intense immunoreaction was
      restricted within the cellular nucleus throughout the brain, suggesting that this
      protein may contribute to the pre-spliceosome assembly in almost all of the
      regions of the brain.

PMID- 9597765
TI  - Role of ions and ion channels in the regulation of Atlantic croaker sperm
      motility.
AB  - The effects of the osmolarity and ionic composition of the external media and ion
      channel blockers on the induction of sperm motility in the marine teleost,
      Atlantic croaker (Micropogonias undulatus) were investigated. An in vitro sperm
      motility assay was developed to determine treatment effects on the percentage of
      motile sperm, sperm speed, and turning rate, using a computer-aided motion
      analysis system. Maximum activation of sperm motility occurred in saline with an
      osmolarity of 680 mOs/kg. Potassium caused a decrease in the percentage of motile
      sperm, but only at high nonphysiological concentrations in the presence of high
      amounts of calcium. Calcium caused an increase in sperm velocity and turning
      rate. Percent motility was inhibited by the potassium-channel blockers, 4
      aminopyridine and veratrine, the calcium-channel blockers, verapamil, diltiazem,
      and nifedipine; the sodium-channel blocker, amiloride, and the chloride-channel
      blocker, ethacrynic acid. In addition, the calcium-channel blockers caused a
      decrease in sperm velocity and turning rate. These results provide evidence for
      the role of potassium, calcium, and possibly sodium, and chloride ions in
      Atlantic croaker sperm motility. In addition, this study demonstrates that
      membrane-bound ion channels are involved in the motility of sperm from a marine
      teleost.

PMID- 9597766
TI  - Microtubule and microfilament dynamics in rat embryos during the two-cell block
      in vitro.
AB  - Developmental block of rat embryo is induced by phosphate at the late two-cell
      stage. The present study uses immunocytochemistry and laser scanning confocal
      microscopy to examine microtubule and microfilament dynamics in blocked and
      nonblocked two-cell-stage rat embryos. Thin fibrous microtubules were distributed
      homogeneously in the cytoplasm in nonblocked embryos during the interphase of the
      two-cell stage and then translocated into mitotic spindles at the M-phase. In
      embryos blocked at the two-cell stage, much thicker fibrous microtubules were
      formed and distributed as rude meshwork structures in the cytoplasm.
      Microfilaments were distributed adjacent to nuclei and along the inside of the
      plasma membrane in nonblocked embryos during the two-cell stage, at M-phase, and
      at cleavage to the four-cell stage. In embryos blocked at the two-cell stage,
      however, microfilaments formed granules and dispersed in the cytoplasm. The
      distribution of microtubules and microfilaments changed relative to the
      occurrence of two-cell block. In summary, these results indicate that both
      microtubules and microfilaments are closely involved in the developmental block
      in two-cell rat embryos.

PMID- 9597767
TI  - A quadrupole ion trap/time-of-flight mass spectrometer with a parabolic
      reflectron.
AB  - A matrix-assisted laser desorption/ionization-quadrupole ion trap/reflectron time
      of-flight (MALDI-QIT/reTOF) mass spectrometer design and its operation in both
      normal and tandem mass spectrometric modes are described. A parabolic reflectron
      was found to be capable of providing mass resolution of 5000 for an initial ion
      energy distribution ranging over a 50% energy interval of the entire reflectron
      energy range. The sensitivity, ion isolation and fragmentation efficiency in the
      MALDI-QIT/reTOF instrument were close to those observed in the MALDI/QIT mass
      spectrometer. The mass resolution was shown to depend on the extraction field
      potentials, the r.f. trapping voltage amplitude and the phase of shutting down
      the r.f. voltage before extraction. At values of qs < 0.3-0.4 the mass resolution
      does not depend on the ion mass, is in a range of 1000-1400 and is governed by
      the extraction voltages and the ion temperature before extraction, the latter
      shown to be in the range 1180-1690 K. The variation of the mass resolution for
      ions at values of qs > 0.4 is irregular but normally it is lower than that for
      ions having lower qs values. Mass spectral line positions shifted when the
      trapping voltage before extraction was varied. The line shifts were larger for
      lower mass ions and were comparable to the line widths in the case of very low
      masses.

PMID- 9597768
TI  - Determination of organ substrate oxidation in vivo by measurement of 13CO2
      concentration in blood.
AB  - Substrate oxidation by various organs in animals as well as in humans is usually
      studied by experiments in which radioactively labeled substrates are used and the
      production of 14CO2 is measured. In vivo, substrate oxidation by an organ has, up
      to now, not been determined by means of stable isotopes. Problems in the
      determination of the concentration of 13CO2 in blood may have impeded the use of
      13C-labeled substrates. For the determination of 13CO2 concentration in blood a
      direct method for the determination of total CO2 concentration in blood was
      combined with the determination of the isotope ratio (13C/12C) of CO2 by isotope
      ratio mass spectrometry. The intra-assay relative standard deviation of the CO2
      concentration (mean: 19.26 mmol l-1; n = 7) was 0.8%. The inter-assay relative
      standard deviation of the CO2 concentration in solutions of a weighed amount of
      Na2CO3 determined over a 5 year period was 0.64% (mean: 21.99 mmol l-1; n = 22).
      The intra-assay relative standard deviation of 13C in CO2 was 0.03% (mean
      13C/12C: 0.0111557; n = 5). From the 13CO2 concentration in arterial and venous
      blood, substrate oxidation by various organs can be calculated. As an
      illustration, the determination of myocardial glucose oxidation in lambs, both at
      rest and during exercise, is described.

PMID- 9597769
TI  - Localization of O-glycosylation sites of MUC1 tandem repeats by QTOF ESI mass
      spectrometry.
AB  - The potential of electrospray mass spectrometry (ESMS) for the sequencing of
      glycopeptides was evaluated using quadrupole time-of-flight (QTOF) technology in
      the MS/MS mode. The location of O-glycosylation sites was possible in the
      positive ion (+) mode by detection of prominent y- and b-fragment ions from the
      underivatized TAP25-2 [T1APPAHGVT9S10APDT14RPAPGS20T21APPA], an overlapping
      sequence of MUC1 tandem repeats which had been glycosylated in vitro by two
      GalNAc residues in the positions T9 and T21. The high mass resolution and
      accuracy of QTOF-(+)ESMS allowed reliable structural assignments. The reduced
      complexity of the fragment spectra and the higher signal-to-noise ratio render
      QTOF-(+)ESMS an alternative mass spectrometric approach to the identification of
      O-glycosylation sites when compared with sequencing by post-source decay matrix
      assisted laser desorption/ionization MS. Diagnostic ions from the N-terminus in
      the b-series offered direct evidence, which was supported by indirect evidence
      from the C-terminus ions of the y-series. The higher glycosylated GalNAc2
      substituted fragments were mainly observed as multiply ionized species.

PMID- 9597770
TI  - Quantitative analysis of 1,3-butadiene-induced DNA adducts in vivo and in vitro
      using liquid chromatography electrospray ionization tandem mass spectrometry.
AB  - 1,3-Butadiene (BD) is a high volume industrial chemical which is known as a multi
      site rodent carcinogen and is classified as a probable human carcinogen. Covalent
      interactions of the reactive epoxy metabolites of BD with DNA lead to the
      formation of DNA adducts which may cause mutations and tumor formation. In the
      present work, liquid chromatography/electrospray ionization tandem mass
      spectrometry (LC/ESI-MS/MS) was employed for analyses of BD-induced DNA adducts
      in vitro and in vivo. Selected reaction monitoring (SRM) using the fragmentation
      of the [M + H]+ ions of the adducts to the corresponding protonated nucleobases
      under collision-induced dissociation was performed. Quantitation was based on
      isotope dilution with 13C- and 15N-labeled internal standards. The methods were
      applied in vitro [calf thymus DNA and TK6 cell cultures treated with epoxy
      metabolites of BD, 3,4-epoxy-1-butene (EB) and diepoxybutane (DEB)] and in vivo
      [DNA isolated from tissues of BD-exposed laboratory animals]. Two regioisomers of
      N-7-EB-guanine adducts, N-7-(2-hydroxy-3-buten-1-yl)guanine (N-7-EB-Gua I) and N
      7-(1-hydroxy-3-buten-2-yl)guanine (N-7-EB-Gua II) and two N-3-EB-adenine isomers,
      N-3-(2-hydroxy-3-buten-1-yl)adenine and N-3-(1-hydroxy-3-buten-2-yl)adenine (N-3
      EB-Ade I and II), were found in EB-exposed samples. N-7-(2',3',4'-trihydroxybut
      1'-yl)guanine (N-7-THB-Gua), N6-(2',3',4'-trihydroxybut-1'-yl)adenine (N6-THB
      Ade), and N-3-(2',3',4'-trihydroxybut-1'-yl)adenine (N-3-THB-Ade) were detected
      in DEB-treated DNA. DNA isolated from liver and lung of rats and mice exposed to
      1250 ppm BD for 2 weeks contained both regioisomers of N-7-EB-Gua and N-3-EB-Ade,
      as well as N-7-THB-Gua and N6-THB-Ade. The methods developed in this work provide
      the means to study accumulation, repair and dose-response relationships of BD-DNA
      adducts in vivo. Although less sensitive than gas chromatography/electron capture
      negative ionization high-resolution mass spectrometry (GC/ECNI-HRMS), LC/ESI(+)
      MS/MS in the SRM mode is extremely useful for analysis of BD-DNA adducts, which
      are not amenable to GC and derivatization owing to the presence of several
      adjacent polar functional groups. Using LC/ESI-MS/MS and isotope dilution,
      multiple structurally diverse BD-DNA adducts can be analyzed simultaneously in
      the same sample with minimal sample preparation.

PMID- 9597771
TI  - Distinction of N-substituted histidines by electrospray ionization mass
      spectrometry.

PMID- 9597772
TI  - Direct sequencing of genomic DNA for characterization of a satellite DNA in five
      species of eastern Pacific abalone.
AB  - A tandemly repeated satellite DNA of 290-291 base pairs (bp) was identified by
      SalI digestion of genomic DNA of five species of Eastern Pacific (California)
      abalone (genus, Haliotis). Following cloning and sequencing of one repeat unit
      from one species, the consensus sequences of this satellite were determined for
      five species by directly sequencing genomic DNA using satellite-specific primers.
      Phylogenetic trees of the consensus satellite sequences had the same topology as
      trees constructed for two abalone sperm acrosomal proteins. In 12 randomly picked
      clones of the Red abalone (H. rufescens) SalI satellite, 16 positions varied, the
      variation being spread throughout the sequence. GenBank database searches found
      no significant similarities between this satellite and known sequences. Southern
      analysis showed that all 290-bp SalI repeats were excised from genomic DNA by
      Sau3A1 digestion. The tandem arrangement of satellite repeats was confirmed by
      sequencing through the SalI site into the next repeat using genomic DNA as
      template, time-dependent appearance of DNA ladders with an approximate 300-bp
      spacing in SalI digests of genomic DNA, and ladders of bands with an approximate
      300-bp spacing generated by polymerase chain reaction (PCR) using genomic DNA as
      template. In the Red abalone, the 290-bp SalI satellite represents approximately
      0.5% of total DNA, equivalent to approximately 28,000 copies per haploid genome.
      The species-specific consensus sequence of this satellite, obtained directly
      using genomic DNA as the sequencing template, provides a molecular marker that
      could be used for identification of hybrid parentage, taxonomy, population
      identification, and forensic studies.

PMID- 9597773
TI  - Universal cytochrome b primers facilitate intraspecific studies in molluscan
      taxa.
AB  - We describe the construction of amplification primers designed to target a
      portion of the mitochondrial cytochrome b locus in a variety of molluscan taxa.
      Combinations of two sets of primers successfully amplified cytochrome b from
      several species of gastropods, bivalves, and cephalopods. Sequence analysis of
      these amplified products revealed nucleotide diversity in small samples within
      several of these taxa. We discuss the utility of these primer sets for studies of
      intraspecific phylogeny in mollusks and potentially other invertebrates.

PMID- 9597774
TI  - Molecular identification of the lobster muscle protein tropomyosin as a seafood
      allergen.
AB  - Crustaceans are a major cause of seafood allergy. Recent studies have identified
      tropomyosin as the major allergen in shrimp. However, such data are lacking in
      other crustaceans. In the present study lobster allergens were identified and
      characterized by molecular cloning, sequencing, and expression. An IgE-reactive
      complementary DNA clone of 2 kilobase pairs (kb) was identified by screening an
      expression library of the spiny lobster Panulirus stimpsoni using sera from
      subjects with crustacean allergy. Expression and sequencing of this clone showed
      that it has an opening reading frame of 274 amino acids, coding for a 34-kDa
      protein designated as Pan s I. In addition, we expressed the fast muscle
      tropomyosin from the American lobster Homarus americanus and found that this
      protein, coined Hom a I, was also recognized by IgE from patients with crustacean
      allergies. The deduced amino acid sequences of Pan s I and Hom a I, which are the
      first identified lobster allergens, show significant homology to shrimp
      tropomyosin. Sera from subjects with crustacean allergies, when preabsorbed with
      recombinant proteins Pan s I or Hom a I, lost their IgE reactivity to muscle
      extract of P. stimpsoni and H. americanus. Preincubation of crustacean allergy
      sera with the recombinant shrimp tropomyosin Met e I also removed their IgE
      reactivity to lobster muscle extracts. The results suggest that patients with
      allergic reactions to crustaceans have common and possibly cross-reactive IgE
      reactive epitopes in lobster and shrimp.

PMID- 9597777
TI  - Restriction digest of PCR-amplified mtDNA from fin clips is an assay for sequence
      genetic "tags" among hundreds of fish in wild populations.
AB  - We tested the feasibility of recovering from wild populations mitochondrial DNA
      genetic "tags" that might result from release of hatchery-reared fingerlings for
      marine stock enhancement. A practical, nondestructive method of genetic "tag"
      recovery would allow quantitative assessment of the efficacy of such programs. A
      rare mtDNA variant with two sites each instead of one for TaqI and RsaI in the
      control region was used as a mock genetic "tag" in snook (Centropomus
      undecimalis). We assayed for the variant among nearly 900 fish by restriction
      digests of DNA amplified by polymerase chain reaction (PCR) obtained from fin
      clip extracts, finding only a single second example of the variant. Thus, mtDNA
      "tags" can be nondestructively assayed for with specificity among hundreds of
      individuals.

PMID- 9597778
TI  - ROn-1 SINEs: a tRNA-derived, short interspersed repetitive DNA element from
      Oreochromis niloticus and its species-specific distribution in Old World cichlid
      fishes.
AB  - A SINE-like repetitive element (ROn-1) has been cloned from the tilapiine cichlid
      fish Oreochromis niloticus. The element is 345 base pairs (bp) in length and
      consists of a transfer-RNA-like domain with putative RNA polymerase III
      recognition sequences, a tRNA-unrelated region, and a poly(A) tail. Approximately
      6000 copies of ROn-1 occur in the haploid genome of O. niloticus. Southern blot
      analysis revealed that ROn-1 is an abundant element in the genomes of many
      African cichlid fishes, but absent from the genome of the Indian cichlid
      Etroplus.

PMID- 9597779
TI  - Identification and preliminary characterization of PCNA gene in the marine
      phytoplankton Dunaliella tertiolecta and Isochrysis galbana.
AB  - The gene coding for proliferating cell nuclear antigen (PCNA) was identified in
      Dunaliella tertiolecta (Chlorophyceae) and Isochrysis galbana (Prymnesiophyceae).
      Southern blot hybridization using a PstI fragment of rat PCNA gene (pCR-1) as a
      probe showed that there is apparently a single copy of this gene per haploid
      genome in both species. On the Northern blot pCR-1 probed a single messenger RNA
      for each species of a molecular size close to rat PCNA mRNA (1.1 kilobases [kb]).
      Polymerase chain reaction (PCR) with a set of degenerated primers produced a
      fragment of about 610 base pairs [bp] from genomic DNA of both species; the PCR
      products appeared close in size to the amplified from rat PCNA and hybridized to
      the pCR-1 probe. Further analysis with reverse transcription-PCR (RT-PCR),
      cloning, and sequencing revealed a complementary DNA of a similar size (616 and
      576 bp) that possesses an open reading frame encoding 205 and 192 amino acids,
      respectively, for Dun (D. tertiolecta) and Iso (I. galbana). Surprisingly, the
      polypeptides deduced from the two cDNA shared no higher homology to each other
      (71%) than to animals such as Xenopus (Dun 72%; Iso 73%), rat (Dun 73%; Iso 74%),
      and human (Dun 73%; Iso 74%), and to higher plants such as soybean (Dun 78%; Iso
      72%), Zea mays (Dun 77%; Iso 73%), and rice (Dunn 77%; Iso 72%), although D.
      tertiolecta has a higher homology (77%) to the Prasinophyceae alga Tetraselmis
      chiu than does I. galbana (71%). The homology to PCNA in budding and fision
      yeasts (63% and 53%, respectively) is also lower than to animals and higher
      plants. It is thus suggested that with regard to PCNA genes, the three algae are
      as different from each other as they are from higher plants and animals. In a
      partially synchronized exponential culture of D. tertiolecta grown with a
      photocycle of 12 h light and 12 h dark, the abundance of the transcript appeared
      to be low at hours 3 and 9 (hour 0 = the onset of light period), and increased
      about 2- to 3-fold at hours 15 and 21 (i.e., during the dark period). Western
      blotting and immunofluorescence analysis on concurrent diel samples showed an
      over 2-fold increase in PCNA protein abundance (in proportion to total cellular
      protein) and the percentage of cells labeled by PCNA antibody. A similar trend
      was found for I. galbana grown under the same conditions. The results suggest
      that the gene transcription was in pace with PCNA synthesis, which was lower in
      the light period when G1 phase was dominant and higher in the dark period when S
      (and probably G2 and early M) phase was dominant, and that the expression of this
      gene may be regulated at the transcriptional level in these two algae.

PMID- 9597780
TI  - Structure and expression of activin genes in rainbow trout.
AB  - Activins are dimeric members of the transforming growth factor-beta (TGF-beta)
      superfamily. By using the polymerase chain reaction (PCR), we have cloned and
      sequenced activin beta A and beta B genes encoding the mature region of the
      peptides from the rainbow trout genomic DNA. Two forms of beta A and a single
      form of beta B-subunits were found. There is high identity with mammalian
      counterparts; the two rainbow trout beta A-subunits have more than 75% nucleotide
      sequence identity with the human beta A-subunit, and the beta B-subunit had 82%
      sequence identity with the human beta B-subunit. Expression of rainbow trout
      activin genes was examined by reverse transcription-PCR (RT-PCR). The major
      expression tissue of rainbow trout activin was ovary and brain at the messenger
      RNA level, and the major expression subunit of rainbow trout activin was the beta
      B subunit.

PMID- 9597781
TI  - Primary biliary cirrhosis: ursodiol effective, but think transplantation sooner.

PMID- 9597782
TI  - Diagnosing Marfan syndrome is still based on clinical characteristics.

PMID- 9597783
TI  - Thrombolysis for acute ischemic stroke: update on the beginning of a revolution.

PMID- 9597784
TI  - Agitated dementia: drug vs nondrug treatment.
AB  - When an elderly patient with Alzheimer's disease or other form of dementia
      exhibits agitated behavior, the caregiver often wants the physician to "do
      something"--i.e., give a neuroleptic drug. Yet, an individualized, rational
      approach to identify and treat the cause of the agitation is more effective. We
      present an algorithm that emphasizes environmental and behavioral therapy.

PMID- 9597785
TI  - Oxygen and aerosolized drug delivery: matching the device to the patient.
AB  - The variety of devices for administering supplemental oxygen and aerosolized
      drugs for hospital inpatients allows physicians to tailor the therapy to
      patient's needs, but presents a challenge in determining which device is best for
      the individual patient. We describe the selection process, appropriate use, and
      the advantages and disadvantages of various devices.

PMID- 9597786
TI  - A 61-year-old woman with thrombocytopenia and a rash.

PMID- 9597787
TI  - Alternative medicine: underevaluated or ineffective?

PMID- 9597788
TI  - Giant cell arteritis: biopsy may not be diagnostic.

PMID- 9597789
TI  - The high cost of terminal care: balancing conflicting goals.

PMID- 9597790
TI  - [Imaging of pathological findings: hepatoma].

PMID- 9597791
TI  - Three-dimensional pressure distribution of the human hip joint--comparison
      between normal hips and dysplastic hips.
AB  - We developed a system for analyzing the three-dimensional contact pressure
      distribution in the human hip joint. Hip joint images obtained by computed
      tomography were loaded into a computer, and the articular surface was
      reconstructed as a three-dimensional polygonal model. The pressure distribution
      of this hip model was then analyzed using a rigid-body spring model. Using this
      system, the three-dimensional pressure distribution in dysplastic hips was
      compared with that in normal hips. Seven dysplastic hips and five normal hips
      were analyzed. In the dysplastic hips, the maximum peak pressure was 5.3 MPa,
      while it was 2.5 MPa in the normal hips. The peak pressure was located at the
      edge of the acetabulum in the dysplastic hips. This system allowed us to easily
      and accurately evaluate the mechanical status of the hip joint. For individual
      patients, the clinical course could be easily predicted and various treatment
      methods could be examined preoperatively.

PMID- 9597792
TI  - Interlocking wedge osteotomy for cubitus varus deformity.
AB  - The authors reviewed 20 patients with cubitus varus deformity who were treated
      with the interlocking wedge osteotomy. All deformities including medial,
      posterior tilt and internal rotation of the distal fragment can be simultaneously
      corrected with this osteotomy. There were 14 males and 6 females whose average
      age was 5.0 years at injury and 14.1 years at surgery. The average follow-up
      period was 37 months. Thirteen patients had excellent results, 6 good, and 1
      poor. The mean carrying angle was improved from 21.5 degrees of varus to 8.8
      degrees of valgus, compared to 9.4 degrees of valgus on the uninjured side. The
      mean flexion of the elbow increased from 123.9 degrees to 134.3 degrees, and the
      mean hyperextension decreased from 12.0 degrees to 7.5 degrees. Three-dimensional
      correction and stable fixation can be achieved with this osteotomy.

PMID- 9597793
TI  - The Governor's Blue-Ribbon Panel on living and dying with dignity.

PMID- 9597794
TI  - Toxicologic teasers: testing your knowledge of clinical toxicology.

PMID- 9597795
TI  - Clinical techniques in crisis intervention: emergency counseling in cases of
      acute poisoning.

PMID- 9597796
TI  - Hawaii Poison Center data reveals a need for increasing hazard awareness about
      household products.
AB  - This study examined for the fiscal years 1995-1996 and 1996-1997, the frequency
      of calls to Hawaii Poison Center related to household products and pesticides
      poisoning, the frequency of the source of calls (professional versus layperson),
      and the patient's age distribution. The data was compared with the data recorded
      in 1989 which was reported earlier in the literature. We found the most frequent
      calls were from general public (6 to 8 times) and were related to household
      products (30% in 1996-97, 39% in 1995-96, and 39% in 1989) involving children
      less than 5 years of age. Results strongly suggest the need for increasing the
      awareness of hazards related to household products amongst the general public.

PMID- 9597797
TI  - "Inside 'da poison center".
AB  - The wide variety of calls received by the Hawaii Poison Center are described.
      These include the typical, humorous and calls unique to the islands. Methods
      include descriptive anecdotal recall and review of Hawaii Poison Center call
      statistics. A brief description of staff, resources and call taking procedures
      are also provided.

PMID- 9597798
TI  - Immunohistochemical diagnosis and significance of forensic neuropathological
      changes.
AB  - Immunohistochemistry is very useful when investigating the cause of death.
      Ischemic cell changes in the hippocampal neurons were not obvious in the brains
      damaged by hypoxic injury. However, it is suggested that even a moderate hypoxia,
      which may affect the neuronal proteins and metabolism, induced astrocytosis in
      the CA3 and CA4 regions, and that in patients with a history of hypoxic attacks
      neuronal damage may be severe even several hours after ischemic injury.
      Furthermore, hsp70 expression was found in the CA2, CA3 and CA4 regions of long
      term survivors after severe hypoxic/ischemic injury. In forensic practice,
      detailed information about the duration and extent of a hypoxic/ischemic injury
      is often unavailable, so that immunohistochemical detection of hsp70 and glial
      cell staining can be of great value in diagnosing not only the hypoxic/ischemic
      injury during the process of death but also the victim's past history of hypoxic
      attacks. In diffuse axonal injury, degeneration of axon and myelin, such as
      swelling and waving, were observed in survivors of more than 8 hours. Retraction
      balls appeared in survivors of more than 1 days. In longer term survivors, such
      as 3 or 5 months, breakdown of myelin and fat-granule cells were observed. In
      addition, retraction balls were also found. Immunohistochemical staining of 200
      kD neurofilament was a very useful method to examine axonal changes, because
      antisera is specific for degenerative neurofilaments. In our study, all cases
      which had pathological findings of diffuse axonal injury (DAI) were associated
      with focal head injuries. From the immunohistochemical staining of neurons in the
      hippocampus, it was suggested that neurons in the hippocampus were injured by
      diffuse brain damage. Furthermore, repairing and protective mechanisms occurred
      especially from CA2 to CA4. It was considered that neuronal damage in diffuse
      brain injury was elucidated not only morphologically but also functionally.
      Therefore, in cases of suspected diffuse brain damage, it is recommended to
      examine the neuronal changes in addition to observing the findings of diffuse
      axonal injury. Immunohistochemical staining of the carotid body is potentially
      very useful for necropsy diagnosis, since it provides a method to detect evidence
      of mechanical asphyxia in suspected cases of manual and/or ligature
      strangulation.

PMID- 9597799
TI  - Measurement of skin color: practical application and theoretical considerations.
AB  - Quantification of erythema and/or pigmentation is important for in vivo
      assessment of skin reactions to external stimuli such as ultraviolet radiation.
      Measurement of lesional color is also useful for quantitative evaluation of the
      efficacy of therapies for skin lesions. Several types of portable optoelectronic
      instruments have recently become available for these purposes and have been
      applied to research in dermatology, physiology, pharmacology, and cosmetic
      science. As color is not a genuine physical quantity but a sensory perception
      based on color vision, any colorimetric data obtained for the skin should be
      interpreted carefully. Erythema and melanin indices derived from skin reflectance
      data should also be evaluated in relation to the optical properties of the skin
      to avoid misuse. In this article, various methods for quantifying skin color and
      related parameters are reviewed and the characteristics of each method are
      discussed theoretically using an optical model of the skin.

PMID- 9597800
TI  - Multiple myeloma: new aspects of biology and treatment.
AB  - Recently, considerable progress has been made in understanding of the biology and
      treatment of multiple myeloma. Molecular genetic abnormalities such as bcl-2,c
      myc, ras, p53, and Rb genes have been identified in this disease and are related
      to a poor prognosis. Cytokine studies have revealed that interleukin-6 is a
      potent growth factor for myeloma cells and is also responsible for the
      progressive bone resorption together with interleukin-1 beta and tumor necrosis
      factor. Myeloablative chemotherapy followed by allogeneic or autologous
      hematopoietic stem cell transplantation has increased the incidence of complete
      remission. However, relapses are still observed because of drug resistance of
      tumor cells. Immunotherapeutic approaches targeting to cell surface antigens and
      interleukin-6 signals are being developed to further eliminate myeloma cells.
      Translating new biological advances into treatment protocols is essential to
      improve the prognosis of multiple myeloma.

PMID- 9597801
TI  - Implications of heat shock/stress proteins for medicine and disease.
AB  - Heat shock/stress proteins (HSPs) are crucial for maintenance of cellular
      homeostasis during normal cell growth and for survival during and after various
      cellular stresses. The HSP70 family functions as molecular chaperones and reduces
      stress-induced denaturation and aggregation of intracellular proteins. In
      addition to the chaperoning activities, HSP70 has been suggested to exert its
      protective action by protecting mitochondria and by interfering with the stress
      induced apoptotic program. The biochemical and functional properties of HSPs
      observed in cultured cells may be relevant to organs and tissues in whole
      animals. The activation of the hypothalamic-pituitary-adrenal axis and the
      sympathetic nerve system elicits the stress response in selected peripheral
      tissues; the HSP70 expression in the vasculature and stomach increases resistance
      against hemodynamic stress and stress-induced mucosal damage, respectively.
      Gastric mucosa pretreated with mild irritants acquires a tolerance against
      subsequent mucosal-damaging insults. This phenomenon is known as "adaptive
      cytoprotection". Transient ischemia also induces ischemic tolerance in the brain
      and heart, which is called "ischemic preconditioning". The heat shock response is
      believed to contribute to the acquisition of the tolerance. The therapeutic
      applications of chaperone inducers that induce HSPs without any toxic effect are
      also introduced.

PMID- 9597802
TI  - Expression of proliferating cell nuclear antigen(PCNA) in biopsy and autopsy
      specimens of gastric carcinoma.
AB  - Although proliferating cell nuclear antigen (PCNA) is known to be an indicator of
      malignant potential in tumors, the biological and clinicopathological
      significance of PCNA in tumor tissue is controversial. METHODS:
      Immunohistochemical expression of PCNA was examined in 58 gastric carcinoma
      tissues obtained at autopsy to test the clinicopathological significance. In
      addition, in 24 of the 58 tumor tissues we compared immunohistochemical
      expression of PCNA in biopsy and autopsy specimens from the same patient in order
      to know whether the proliferating activity of tumor cells is stationary from the
      early stage to the end of tumor growth. RESULTS: 1. PCNA was undetectable in some
      tumor tissues (12.5% in biopsy and 10.3% in autopsy specimens). 2. the frequency
      of PCNA positive cases and labeling index (LI) (%) of PCNA in tumor tissues were
      not significantly different between biopsy and autopsy specimens. 3. the
      intensity of PCNA reaction was not related to prognosis. 4. PCNA positive cases
      and LI did not correlate with survival condition. CONCLUSION: It is hard to say
      whether PCNA is a reliable indicator in predicting malignancy and prognosis of
      gastric cancer.

PMID- 9597803
TI  - Light and electron microscopic immunocytochemistry on the localization of 17
      alpha-hydroxylase/C17,20-lyase (P450c17) in the rat placenta.
AB  - The rat placenta is the primary source of androgens during the second half of
      pregnancy. Androgens are converted to estrogens in the ovaries and contribute to
      the maintenance of normal pregnancy. We immunocytochemically characterized the
      cellular and subcellular localization of cytochrome P450 of 17 alpha
      hydroxylase/C 17,20-lyase (P450c17), an enzyme responsible for androgen
      synthesis, in the rat placenta. We also observed the fine structure of the
      placenta by electron microscopy. The rat placenta had a different structure from
      the primate, and contained four zones: labyrinth, basal zone, decidua basalis,
      and metrial gland. The labyrinth had three trophoblastic layers and fetal
      endothelium, and P450c17 immunoreactivity was homogeneously localized in the
      three trophoblastic layers but not in the fetal endothelium. In the basal zone,
      various types of trophoblasts were observed, and the immunoreaction was localized
      in small basophilic cells and giant cells. The intensity of staining was
      heterogeneous among these cells. The decidua basalis showed no immunostaining.
      Subcellular localization of the enzyme was in the cytoplasm, but not in the
      nucleus or mitochondria. The present study demonstrated a steroidogenic potency
      in both the labyrinth and the basal zone, although it was shown only in the basal
      zone in previous studies.

PMID- 9597804
TI  - The effects of qi-gong and acupuncture on human cerebral evoked potentials and
      electroencephalogram.
AB  - Although a number of studies on traditional Chinese medicine, such as qi-gong
      (QG), acupuncture (AC), moxibustion and Chinese herbal drugs, have been reported
      in recent years, there are few reports on human cerebral evoked potentials (EPs),
      especially relating only to QG and AC. In the present study, we examined the
      changes in EPs and electroencephalogram (EEG) by QG, and by AC stimulation to the
      point called "Zusanli" on the left lower leg, with one healthy male adult. 1.
      With regard to the effect of QG, significant changes in EP-components originated
      from the cortex suggest both facilitating and inhibitory effects of QG on the
      cortex. However, no significant changes in EP-components originated from the
      subcortex and no significant changes in EEG power% suggest that QG does not
      affect the subcortex. 2. With regard to the effects of AC, significant changes in
      EP-components originated from the cortex suggest facilitating and inhibitory
      effects of AC stimulation on the cortex. Furthermore, it is suggested that AC
      stimulation has few effects on the somatosensory and the visual pathways up to
      the cortex, while it has complicated effects on the auditory pathway up to the
      cortex.

PMID- 9597805
TI  - A subcutaneous tissue reaction in the early stage to a synthetic auditory ossicle
      (Bioceram) in rats.
AB  - The discs of synthetic auditory ossicle (Bioceram), which are composed of
      aluminium oxide (Al2O3), were implanted subcutaneously in the interscapular
      region of 16 rats. The implanted specimens were removed at 1, 3, 7 and 14 days
      after implantation. The decalcified 6 microns thick sections were stained with
      H.E. and cell types around the implants were counted microscopically. We found
      that an acute inflammatory reaction occurred at one day, in which macrophages and
      neutrophiles predominated, and almost disappeared at about 7 days after
      implantation. Fibrosis began to be observed at 3 days. During this early stage,
      foreign body giant cells were found in only one specimen at 3 days. These
      findings, in comparison with those in the controls, showed that the chemical
      irritation of Bioceram to the subcutaneous tissue is slight, although the
      physical and/or chemical irritation of Bioceram lasts continuously and induces
      fibrosis around the bioimplant. The results so far suggest that Bioceram seems to
      be a satisfactorily biocompatible material, at least within the extent of 2
      weeks.

PMID- 9597806
TI  - Immunohistochemical localization of thyroid hormone nuclear receptors in human
      hair follicles and in vitro effect of L-triiodothyronine on cultured cells of
      hair follicles and skin.
AB  - To investigate the cellular basis of the action of thyroid hormone on hair
      follicles, we studied the immunohistochemical localization of thyroid hormone
      receptors (TRs) in human scalp skin using a mouse monoclonal antibody, TR alpha 1
      (C4) against TRs. Immunoreactive TRs were detected in the nuclei of the outer
      root sheath cells (ORSCs), dermal papilla cells (DPCs), fibrous sheath cells of
      hair follicles, hair arrector pili muscle cells and sebaceous gland cells.
      However, nuclei of hair matrix cells were not clearly stained with TR alpha 1
      (C4). The epidermis showed positive nuclear staining by the antibody. Ductal and
      secretory portions of eccrine sweat glands were also stained with the antibody as
      we had expected. In the dermis, almost all the cell components including
      fibroblasts, vascular endothelial and smooth muscle cells, and Schwann cells were
      positively stained. Immunofluorescence also showed TRs expression in cultured
      ORSCs, DPCs, epidermal keratinocytes and dermal fibroblasts. L-triiodothyronine
      stimulated the proliferation and/or metabolism of all these four types of cells
      significantly, although there was variation at the rate of stimulation. Whereas,
      structurally similar, but metabolically inactive analog, reverse T3 had no
      effect. These results demonstrate the presence of thyroid hormone nuclear
      receptors in human hair follicles. Furthermore, the presence of TRs in different
      cell types in the skin suggests numerous direct effects of thyroid hormone on
      this target tissue.

PMID- 9597807
TI  - The role of cyclosporin A on antibody-dependent monocyte-mediated cytotoxicity
      against human multidrug-resistant cancer cells.
AB  - A P-glycoprotein (P-gp) inhibitor, cyclosporin A (CsA) was found to enhance the
      susceptibility of multidrug resistant (MDR) cancer cells to anti-P-gp antibody
      dependent cellular cytolysis (ADCC) by monocytes, but the exact mechanism is
      unknown. In this study, we examined whether CsA enhanced the susceptibility of
      MDR cells through its inhibitory effect of P-gp function by using anti
      ganglioside GM2 (GM2) monoclonal antibody (Ab), KM966, instead of anti-P-gp Ab,
      MRK16. Monocyte-ADCC induced by both KM966 and MRK16 against P-gp positive human
      MDR ovarian cancer cells was significantly augmented by addition of CsA. KM966,
      but not MRK16, induced monocyte-ADCC against P-gp negative human ovarian cancer
      cells and CsA enhanced this ADCC activity, indicating that suppressive effect of
      P-gp function by CsA was not essential to the enhancement of ADCC. Moreover,
      pretreatment of tumor cells with CsA augmented their susceptibility to monocyte
      ADCC irrespective of P-gp expression. Interestingly, KM966 or MRK16 induced
      monocyte-ADCC against various human lung cancer cells expressing either GM2 or P
      gp, but CsA did not affect these ADCC. These findings suggest that CsA may
      enhance the susceptibility to the monocyte-ADCC of ovarian cancer cells, but not
      of lung cancer cells, irrespective of its suppressive effect of P-gp function.

PMID- 9597808
TI  - Activation of 1-nitropyrene by nitroreductase increases the DNA adduct level and
      mutagenicity.
AB  - 1-Nitropyrene (1-NP) is a mutagenic nitro compound in the environment. We studied
      correlations between the mutagenicity of 1-NP for three strains of Salmonella
      typhimurium, the activity of bacterial nitroreductases and the amount of 1-NP
      derived DNA adducts. Bacterial strains used in this study were S. typhimurium
      strains TA98, nitroreductase-less mutant TA98NR and YG1021 carrying a
      nitroreductase-producing plasmid. The mutagenicity of 1-NP was measured using the
      Ames assay, and the nitroreductase activities of these strains were assayed by
      quantification of 1-aminopyrene produced from 1-NP. The DNA adducts were measured
      by the 32P-postlabeling method. Among the three bacterial strains, strain YG1021
      was the highest in mutagenicity of 1-NP, the nitroreductase activity and the DNA
      adduct level. However, S. typhimurium strain TA98NR had the lowest values of
      these three parameters. Nitroreductase activity, DNA adduct level and
      mutagenicity were strongly correlated with each other. These results indicate
      that bacterial nitroreductase plays an important role in forming the DNA adducts,
      and that the higher the adduct level the higher the level of mutagenicity.

PMID- 9597809
TI  - Total parenteral nutrition on energy metabolism in children undergoing autologous
      peripheral blood stem cell transplantation.
AB  - The resting energy expenditure (REE) and the respiratory quotient (RQ) were
      measured longitudinally using indirect calorimetry to examine the effects of
      total parenteral nutrition (TPN) on energy metabolism in children undergoing
      autologous peripheral blood stem cell transplantation (PBSCT). There were six
      children (two males and four females) and the age ranged from five to 13 years
      (median, eight yrs). The diagnosis included acute lymphocytic leukemia (ALL; 4),
      neuroblastoma (NBL; 1) and primitive neuroectodermal tumor (PNET; 1). TPN was
      started after the patients were stabilized following PBSCT (group A; n = 3) or
      before the initiation of high-dose cytoreductive chemotherapy (HCC) (group B; n =
      3). Duration of HCC before PBSCT was identical between the two groups (six to
      eight days). Average total calorie and protein intake during HCC was
      significantly higher for group B than for group A. The %REE, the percentage of
      REE to the predicted basal energy expenditure (BEE), in group A showed 133 +/-
      19%, 129 +/- 14% and 146 +/- 11% during three periods of HCC (days -8 to -1 of
      PBSCT), bone marrow suppression (days 0 to 11 of PBSCT) and bone marrow recovery
      (days 12 to 22 of PBSCT), respectively. In contrast, those in group B were 10% to
      20% lower than those in group A at all periods. Carbohydrate oxidation rates
      during HCC in group A were significantly lower than those in group B, and those
      were not different between both groups during post-PBSCT periods. Fat oxidation
      rates in both groups were similar at all stages of periods. In contrast, protein
      degradation rates in group A were significantly higher than those in group B at
      all stages of the period. From these results, we concluded that commencement of
      TPN administration prior to HCC in the patients undergoing PBSCT provides
      beneficial effects to maintain better energy metabolic and nutritional status.

PMID- 9597810
TI  - Effect of clarythromycin on the distant metastases of human lung cancer cells in
      SCID mice.
AB  - Recently, the use of macrolides is suggested to be therapeutically effective in
      prolonging the survival of patients with inoperable non-small cell lung cancer.
      The purpose of this study was to examine therapeutic effects of a macrolide,
      clarythromycin (CAM) on the metastastic developments of two different human non
      small cell lung cancers (squamous cell lung carcinoma RERF-LC-AI, and
      adenocarcinoma PC-14) in severe combined immunodeficient (SCID) mice depleted or
      undepleted of natural killer (NK) cells, respectively. CAM, injected
      subcutaneously at doses of 5 and 10 mg/kg body weight/day from day 7 to 41 after
      i.v. inoculation of human lung cancer cells, was not effective in inhibiting
      their distant organ metastases in SCID mice. CAM at concentrations of less than
      10 micrograms/ml did not have a direct influence on the proliferation of these
      tumor cells in vitro. Although CAM alone was not effective in augmenting NK
      activity, it augmented the IL-2-induced killer (LAK) activity against Daudi cells
      in vitro. These results suggest that CAM alone may not be enough to control the
      spread of non-small cell lung cancer in the patient with T cell dysfunction.

PMID- 9597811
TI  - Suppression of HIV-1 replication in peripheral blood mononuclear cells by
      fasudil.
AB  - Fasudil is a potent inhibitor for various protein kinases such as myosin light
      chain kinase and protein kinase C. It has been used as a drug for improvement of
      intracranial vasospasm and following ischaemic diseases. In this report, we
      demonstrate that fasudil suppressed the replication of human immunodeficiency
      virus type 1 (HIV-1) in mitogen-activated peripheral blood mononuclear cells. Our
      finding shows that fasudil may be useful as a new and distinct chemotherapeutic
      agent against HIV-1 infection.

PMID- 9597812
TI  - Hepatosplenic gamma delta T-cell lymphoma associated with hepatitis B virus
      infection.
AB  - Hepatitis B virus (HBV) infection has been implicated in the development of
      hepatocellular and hematopoietic malignancies. We describe a patient with chronic
      hepatitis B who developed hepatosplenic gamma delta T-cell lymphoma. A 45-year
      old woman presented with marked hepatosplenomegaly and hepatic failure during the
      course of chronic hepatitis B. Peripheral blood examination revealed 57% abnormal
      lymphoid cells which expressed the gamma delta T-cell receptor. The cytogenetic
      analysis of tumor cells showed an abnormal karyotype; 47, XX, -13, +2mar in all
      20 metaphases examined. A clonal rearrangement of the T-cell receptor genes was
      demonstrated by Southern blot analysis, showing monoclonal expansion of tumor
      cells. A liver biopsy specimen showed fibrosis of the portal areas and sinusoidal
      infiltration of tumor cells. HBV infection was documented by the presence of IgG
      anti-HBc and anti-HBs antibodies in serum. Although HBV-DNA was not detected in
      tumor cells by polymerase chain reaction analysis, there is a possibility that
      proliferation of gamma delta T cells in response to HBV infection played a role
      in the pathogenesis of hepatosplenic gamma delta T-cell lymphoma.

PMID- 9597813
TI  - Can the liver with Gilbert's syndrome be used as graft of living-related liver
      transplantation?
AB  - Gilbert's syndrome is the common cause of non hemolytic unconjugated
      hyperbilirubinemia with a prevalance of 3-7%. Gilbert's syndrome may introduce a
      selection of potential liver donors from brain death patients. We present a case
      of living-related liver transplantation (LRLT) from a donor with Gilbert's
      syndrome. A 22-year-old woman had been diagnosed as having liver cirrhosis at the
      age of 5. She underwent liver transplantation with the donor's left lobe as the
      graft. The donor, who was the father of the patient, had been diagnosed with
      Gilbert's syndrome. Although the recipient was well until 11 months after
      surgery, she died of subacute fulminant hepatitis 16 months after surgery.
      However, it was clear that the liver with Gilbert's syndrome could be used as a
      graft of living-related liver transplantation for adult recipients.

PMID- 9597814
TI  - Bone tumors.

PMID- 9597815
TI  - Patient satisfaction after limb-sparing surgery and amputation for pediatric
      malignant bone tumors.
AB  - We surveyed 65 patients age 13 years or older who had been treated for malignant
      bone tumors and were in remission at least 1 year after limb-sparing surgery (LS)
      or amputation (AMP) to assess general satisfaction with the surgical outcome and
      its impact on various areas of functioning. Of 130 eligible patients, 65
      responded (61 treated for osteosarcoma, 3 for Ewing's sarcoma, and 1 for
      mesenchymoma). The median current age of the cohort was 25.8 years (range, 14.2
      to 47.5 years). The median time from surgery was 14.2 years (range, 4.0 to 30.4
      years) for the AMP group, and 5.5 years (range, 2.0 to 13.8 years) for the LS
      patients. Questionnaire responses of patients treated with AMP compared to those
      who had LS surgery showed no significant differences in the impact of the
      surgical procedure on educational and occupational status, functional
      limitations, pain intensity and degree of pain interference, emotional distress,
      interpersonal/social interactions and self-image, rehabilitation experience, and
      overall satisfaction with the surgical procedure. Functional limitation was
      significantly related to pain interference, as well as emotional distress, self
      image, and interpersonal difficulties for the entire cohort. Our findings
      highlight procedure-related advantages and difficulties that may potentially
      enhance decision making regarding the selection of the surgical procedure for
      individual patients with malignant bone tumors of an extremity.

PMID- 9597816
TI  - Late effects in survivors of bone tumors.
AB  - Today more than 71% of children with cancer are surviving their disease. This is
      because of improved treatment including aggressive combination therapy and better
      supportive care measures. The majority of patients with bone tumors are now being
      treated with surgery, chemotherapy, and radiation therapy, resulting in an
      increase in numbers of long-term survivors. This aggressive therapy, however, has
      increased the risk of developing late effects. This article reviews some of these
      late effects in survivors of bone tumors diagnosed in childhood or adolescence.
      Areas that are explored include cardiac, infections, second operations, second
      malignant neoplasms, renal, auditory, fertility, pulmonary, functional, and
      psychosocial outcomes. The need for long-term follow-up clinics is also
      addressed.

PMID- 9597817
TI  - Historical perspective of the treatment of osteosarcoma: an interview with Dr
      Norman Jaffe. Interview by Margaret Pearson.

PMID- 9597818
TI  - 153Sm-EDTMP.

PMID- 9597819
TI  - A review of the past, present, and future clinical trials from the Children's
      Cancer Group.

PMID- 9597820
TI  - On being there.

PMID- 9597821
TI  - Note on the non-homogeneous Prendiville process.
AB  - By creating an auxiliary process, this note obtains complete solution to the
      distribution of the non-homogeneous Prendiville process. In addition, an error in
      the literature of the original Prendiville process is corrected.

PMID- 9597822
TI  - Singular homoclinic bifurcations in tritrophic food chains.
AB  - The Rosenzweig-MacArthur food chain model is proved to have homoclinic orbits.
      The proof is in two steps. First, we use a geometric approach based on singular
      perturbation and detect singular homoclinic orbits as well as parameter
      combinations for which these orbits exist. Second, we show, numerically, that for
      slightly different parameter values there exist also nonsingular homoclinic
      orbits that tend toward the singular ones when the time responses of the three
      trophic levels are extremely diversified. The analysis is performed without
      exploiting too deeply the mathematical structure of the Rosenzweig-MacArthur
      model. This is done intentionally, to assist readers interested more in the
      methodology than in the application to food chains.

PMID- 9597823
TI  - A procedure for generating locally identifiable reparameterisations of
      unidentifiable non-linear systems by the similarity transformation approach.
AB  - A method is presented for the generation of locally identifiable
      reparameterisations of non-linear systems which have been shown to be
      unidentifiable via application of the similarity transformation approach. The
      existence of the reparameterised system in terms of the maximum permissible
      number of locally identifiable parameters is provided and is crucially dependent
      upon the ability to find the rank deficiency of an appropriate (and possibly
      infinite) jacobian matrix. The reparameterisation procedure is described in
      detail, and is illustrated with application to two known non-trivial examples of
      unidentifiable non-linear systems.

PMID- 9597824
TI  - Oscillations of two competing microbial populations in configurations of two
      interconnected chemostats.
AB  - It is known that, when two microbial populations competing for a single rate
      limiting nutrient are grown in a spatially uniform environment, such as a single
      chemostat, with competition being the only interaction between them, they cannot
      coexist, but eventually one of the two populations prevails and the other becomes
      extinct. Spatial heterogeneity has been suggested as a means of obtaining
      coexistence of the two populations. A configuration of two interconnected
      chemostats is a simple model of a spatially heterogeneous environment. It has
      been shown that, when Monod's model is used for the specific growth rates of the
      two populations, steady-state coexistence can be obtained in such systems for
      wide ranges of operating conditions. In the present work, we study a model of
      microbial competition in configurations of interconnected chemostats and we show
      that, if a substrate inhibition model is used for the specific growth rates of
      the two populations, coexistence in a periodic state is also possible. The
      analysis of the model is done by numerical bifurcation theory methods.

PMID- 9597825
TI  - Fast game theory coupled to slow population dynamics: the case of domestic cat
      populations.
AB  - We study a deterministic model of a population where individuals alternatively
      adopt hawk and dove tactics. It is assumed that the hawk and dove individuals
      compete for some resources at a fast time scale. This fast part of the model is
      coupled to a slow part that describes the growth of the population. It is shown
      that, in a constant game matrix, the population grows according to a logistic
      curve whose r and K parameters are related to the payoff of the tactics. Results
      show that the highest population density is obtained when all individuals are
      dove. We also study a density-dependent game matrix for which the gain is a
      function of the population density. In this case, we show that two stable
      equilibria can occur, a first one at low density with a high proportion of hawk
      individuals and a second one at large density with a low proportion of hawk
      individuals. Our model is applied to domestic cat populations for which the
      behavior of individuals in competition with one another can be modeled by two
      tactics: hawk and dove. Such tactics change with density of population. The
      results of the model agree well with observed data: high-density populations of
      domestic cats are mainly doves, whereas low-density populations are mainly hawks.

PMID- 9597826
TI  - The effect of pair formation and variable infectivity on the spread of an
      infection without recovery.
AB  - For the spread of an infection without recovery we compare the properties of a
      model in which contacts are assumed to be instantaneous and every contact is with
      a new partner to a model with an explicit description of partnership formation
      and duration. We investigate the dynamic behaviour at the beginning of the
      epidemic, the exponential growth phase and the endemic equilibrium in a
      population with a simple demographic process. Comparisons are made with the
      assumption that the basic reproduction ratio R0 is equal for both models. In a
      second step we introduce variable infectivity into both models and investigate
      how that interacts with the process of pair formation and partnership duration.
      The main results are: If partnership duration is taken into account, then (a) the
      prevalence may initially decrease, even if R0 > 1; (b) the exponential growth
      rate is lower than in a model without partnership duration; (c) the endemic
      equilibrium is higher than in a model without partnership duration. Furthermore
      we show that for a model with positive partnership duration for one value of R0
      one might have more than one corresponding epidemic growth rate and endemic
      steady state. This implies that one cannot estimate R0 from the endemic level
      without further information on the partnership process. Finally we demonstrate
      that even for a very low value of per contact infectivity in the second stage of
      infection, as has been postulated for HIV-infection, transmission during the
      second stage may contribute significantly to the spread of the epidemic due to
      the long duration of the second stage. Therefore, reduction of the high
      infectivity in the short first stage of infection only affects R0 markedly if
      average partnership duration is short.

PMID- 9597827
TI  - A tale of Danbury hatters, detectives and Dartmouth chemists.

PMID- 9597828
TI  - Molecular genetics: impact on prenatal diagnosis.

PMID- 9597829
TI  - Screening for birth defects: integrating laboratory evaluation, genetic
      counseling and clinical intervention.

PMID- 9597830
TI  - Preventing birth defects: the challenges of diabetic fetotherapy and neural tube
      defects.

PMID- 9597831
TI  - Prenatal diagnosis: the role of the genetic counselor.

PMID- 9597832
TI  - Detection and management of the intrauterine growth restricted fetus.

PMID- 9597833
TI  - Managing AIDS in pregnancy.

PMID- 9597834
TI  - Deep venous thrombosis and pulmonary embolism in pregnancy.

PMID- 9597835
TI  - Esophageal perforation from Maloney dilator following esophageal biopsy.

PMID- 9597836
TI  - Health care quality improvement in Rhode Island: a methodology.

PMID- 9597837
TI  - Low birth weight births delivered at the regional perinatal center.

PMID- 9597838
TI  - Tobacco use prevention in pediatric primary care settings.

PMID- 9597839
TI  - Operation Pacific Haven: humanitarian medical support for Kurdish evacuees.
AB  - This article reviews the medical aspects of the humanitarian assistance mission
      Joint Task Force Operation Pacific Haven from September 1996 to April 1997. It
      reviews the effectiveness of the deployable medical units used to support the
      medical screening, treatment, and processing of more than 6,600 Kurdish evacuees
      applying for political asylum in the United States. The distinct cultural mores
      and language barriers of the Kurdish population made the provision of even basic
      medical care a challenge. Designed for combat service support, these deployable
      medical units were successful in the performance of the comprehensive public
      health and humanitarian assistance medical support mission because of the support
      of two on-island military treatment facilities. In short, for military medicine
      to successfully conduct humanitarian assistance and/or disaster relief missions,
      deployable medical units need to be designed, equipped, staffed, and trained to
      perform these operations.

PMID- 9597840
TI  - Military preventive medicine and medical surveillance in the post-cold war era.
AB  - In response to the end of the cold war, the United States developed new foreign
      policy and national security strategies. As a result, many medical support
      concepts that were operative during the cold war were invalidated. Recently, the
      Chairman of the Joint Chiefs of Staff provided direction and guidance for long
      range strategic planning (Joint Vision 2010). Medical support doctrine that is
      being developed within the framework of Joint Vision 2010 relies on currently
      unavailable preventive medicine and medical surveillance capabilities. This
      report analyzes the relevance and roles of military preventive medicine and
      medical surveillance in the context of post-cold war resource constraints and
      military medical support needs, presents the rationale for and objectives of a
      demand-reduction medical support strategy, and outlines the roles,
      responsibilities, and characteristics of a defense medical surveillance system.

PMID- 9597841
TI  - Use of medical specialties in medical operations other than war: lessons from
      Saudi Arabia.
AB  - From the experience of a U.S. Army Air Defense Artillery "battalion-plus" task
      force serving a 6-month rotation in the Kingdom of Saudi Arabia, we compiled the
      requirements for specialty consultations on deployed personnel in the
      predeployment screening phase, during deployment (including both inpatient
      hospitalizations and medical evacuations), and immediately upon return to home
      station. We required a wide variety of specialty expertise. In every phase of the
      operation, we consulted orthopedic surgery most often. Nonsurgical and surgical
      specialists were consulted in roughly equal numbers. Almost every field of adult
      medicine was represented in our sample. The distribution of consultations across
      specialties differs from what would be expected in combat but is similar to that
      seen in the few other studies of comparable populations. Excellent host nation
      support allowed us to use specialty expertise to an almost ideal extent. These
      data represent the most complete "snapshot" that has been taken of the
      requirements for specialty medical consultations in a military operation other
      than war (MOOTW). They demonstrate that under MOOTW conditions, even a healthy
      Army population requires the assistance of a full panel of medical specialties.
      They should serve as a benchmark for planners estimating the medical specialty
      needs that the Army must provide. Military medicine must provide access to
      essentially all medical specialties for personnel deployed under MOOTW
      conditions, whether through host nation support, telemedicine, or medical
      evacuation.

PMID- 9597842
TI  - The health and physical readiness of Army reservists: a current review of the
      literature and significant research questions.
AB  - Individual soldier combat readiness through enhanced physical fitness is a major
      emphasis in the United States military today. Unfortunately, the prevalence of
      cigarette smoking, alcohol abuse, and other poor health practices continues to be
      reported at higher rates for active duty military personnel than for civilian
      populations. There is a dearth of research about health and fitness in the Army
      Reserve. Changing trends point toward more rapid mobilization of reservists for
      peacekeeping and combat missions throughout the world; however, it is important
      to remember that the Army Reserve is unique in its blending of both military and
      civilian occupational environments. The purpose of this paper is to review the
      current literature regarding Army Reserve health behaviors and physical
      readiness. Examples of significant future research questions are provided. More
      studies are needed to assess both individual motivational activities and
      organizational values that enhance health-promoting efforts. Interventions can
      then be designed to eliminate impediments to health and endorse specific
      organizational values and interpersonal skills that increase healthy behaviors.

PMID- 9597843
TI  - The Uniformed Services University of the Health Sciences, F. Edward Hebert School
      of Medicine: status of the Federal Medical School after 25 years.
AB  - In its first 25 years, the Uniformed Services University of the Health Sciences
      (USUHS) has become a quality institution of medical education that provides a
      steady flow of career physicians for the military. It compares favorably with
      U.S. medical school averages in all aspects of undergraduate medical education:
      faculty, teaching facilities, matriculants, curriculum, student performance, and
      cost. USUHS provides excellent medical education and adds unique preparation for
      uniformed public service. It also provides military-specific graduate education,
      graduate medical education, continuing health education, medical research,
      clinical services, consultation, public service, and ties with international
      military, medical, and research institutions.

PMID- 9597844
TI  - The first four years of the Uniformed Services University of the Health Sciences
      Graduate School of Nursing.
AB  - The Graduate School of Nursing (GSN) was established at the Uniformed Services
      University of the Health Sciences in 1993 to prepare advanced practice nurses,
      namely family nurse practitioners (FNPs) and nurse anesthetists (CRNAs), for the
      uniformed services. A study of needs for nurses in the uniformed services in
      these specialties indicated that by the year 2000 there would be a need requiring
      a total enrollment in educational programs of 268 CRNAs and 100 FNPs over a 5
      year period. Offering the master of science in nursing degree, the GSN has
      enrolled 61 students in its two programs, and by the end of the 1997 academic
      year, it will have graduated 19 FNPs and 19 CRNAs. The GSN was authorized by the
      Department of Defense, Office of Health Affairs, in February 1996. Federal
      nursing chiefs serve as advisors to the GSN. The GSN received full accreditation
      from the Council on Accreditation of Nurse Anesthesia Educational Programs in
      1994 and from the National League for Nursing in December 1996. All students who
      have graduated have successfully passed their certification examinations.
      Supplementing other educational resources, the GSN is helping to meet the
      educational needs of the uniformed nursing services by introducing pilot programs
      specifically designed to meet these needs.

PMID- 9597845
TI  - Physiological effects of thermal stress on aviators flying a UH-60 helicopter
      simulator.
AB  - An evaluation of the physiological effects on aviators of heat stress (90 degrees
      F wet bulb globe temperature [WBGT]) versus a cooler condition (70 degrees F
      WBGT) when wearing either a MOPP0 (Mission-Oriented Protective Posture 0) uniform
      or a MOPP4 ensemble encumbered with a ballistic chest plate and overwater
      survival gear was performed at the United States Army Aeromedical Research
      Laboratory. The study used a repeated-measures design with 14 aviators flying 4
      hour missions in a UH-60 helicopter simulator. Average crew endurance in the
      MOPP4-hot condition was reduced to one-third of the fully completed mission time
      of 309 minutes. For the hot condition, core temperature in the simulator rose 1.4
      degrees F/hour when aviators wore the encumbered MOPP4 ensemble versus 0.27
      degree F/hour when they wore the MOPP0 uniform. Sweating rate in the MOPP4-hot
      condition was 1,523 ml/hour, resulting in 2.5% dehydration, in contrast to 183
      ml/hour and 0.9% dehydration in the MOPP4-cool condition. In this study, pilots
      flying realistic UH-60 simulator sorties rapidly incurred significant
      physiological heat strain when wearing an encumbered MOPP4 flight ensemble in hot
      cockpit conditions.

PMID- 9597846
TI  - Generalizability in pregnancy and work research.
AB  - Generalizability of findings is a critical issue in research on pregnancy and
      work. The characteristics of a sample of 350 pregnant military women were
      compared with those of the populations of active duty women and active duty
      pregnant women. The sample was fairly representative in terms of minority status
      and age. The sample differed somewhat in terms of branch of service, rank, and
      marital status. Comparisons of demographics and pregnancy planning between
      military and civilian pregnant women supported generalizability. Unique aspects
      of military service and different access to health care among civilian pregnant
      women warrant caution in generalizing of findings.

PMID- 9597847
TI  - A new wellness center concept: integration of the physical therapy and the
      morale, welfare, and recreation departments.
AB  - This case study describes the implementation of a wellness center based on the
      integration of a Navy outpatient physical therapy department and a morale,
      welfare, and recreation cardiovascular center. The logistics and services
      provided are discussed. The productivity of the physical therapy department based
      on the monthly number of patient treatments is assessed. A statistically
      significant increase in patient visits of 38% above the previous year was noted.
      The newly established cardiovascular center averaged 1,500 client visits monthly.
      This unique collaboration appears to hold promise as an effective wellness center
      concept.

PMID- 9597848
TI  - Venomous snakebite in Thailand. I: Medically important snakes.
AB  - Thailand has an abundance of venomous snakes. Among the neurotoxic family
      Elapidae, there are three species of the genus Naja (cobras), three of the genus
      Bungarus (kraits), and the king cobra of the genus Ophiophagus. Other Elapidae
      snakes in Thailand include sea snakes and Asian coral snakes of the genus
      Calliophis. They have potent venoms but rarely bite humans. Tissue and hemotoxic
      snakes are represented by family Viperidae, subfamilies Viperinae and Crotalinae.
      They remain an occupational hazard for farmers and rubber tappers, causing
      serious morbidity but only rare deaths, since competent treatment is now widely
      available throughout Thailand. Purified equine antivenin is manufactured locally
      for the monocled and Siamese spitting cobras (Naja kaouthia and N. siamensis),
      king cobra (Ophiophagus hannah), banded krait (Bungarus fasciatus), most green
      pit vipers (Trimeresurus sp.), Malayan pit viper (Calloselasma rhodostoma), and
      the Siamese Russell's viper (Daboia russelli siamensis).

PMID- 9597849
TI  - Venomous snakebite in Thailand. II: Clinical experience.
AB  - We reviewed a total of 2,525 snakebite patients in Bangkok. Of these, 1,415 were
      bitten by venomous snakes, 91 by neurotoxic snakes of genus Naja or Bungarus and
      1,324 by snakes of family Viperidae or Crotalidae. Seventy-one percent of bites
      were on the lower extremity. There were two fatal cobra bites; both patients were
      dead on arrival at the hospital. Bites from vipers caused morbidity but no
      deaths. Species-specific antivenins are effective in reversing respiratory
      failure from cobra bites and coagulopathies from bites by Viperidae and
      Crotalidae snakes. However, early respiratory and wound care will save lives even
      in the absence of specific cobra and krait antivenin. Care of a snakebite victim
      should consist of immobilization and bandaging of the bitten limb with elastic
      bandages during transport to the hospital, early surgical debridement of necrotic
      tissue, appropriate infusion of antivenin, aggressive respiratory support,
      management of shock and infection, and peritoneal dialysis or hemodialysis.
      Incision of bite wounds, suctioning, application of ice, and tourniquets are of
      no proven value and may be dangerous. All snakebite victims in southeast Asia
      should survive if they receive early competent care.

PMID- 9597850
TI  - Safety and efficacy of DEET and permethrin in the prevention of arthropod attack.
AB  - Many preventable diseases affecting troop strength are directly attributed to
      disease-carrying insects. The first line of defense against arthropod vectors is
      the use of personal protective measures. The concurrent application of DEET (N,N
      diethyl-m-toluamide) repellent on the skin and permethrin [(3-phenoxy
      phenyl)methyl(+/-)cis,trans-3-(2,2-dichloroethenyl)-2, 2- dimethylcyclopropane
      carboxylate] insecticide on the battle dress uniform, while the uniform is worn
      properly, is a personal protective strategy officially known as the DOD Insect
      Repellent System. It is important for troop commanders and field leaders to
      enforce the use of personal protective measures to prevent insect-borne
      infectious diseases and to ensure troop and soldier readiness. DEET is a safe and
      effective repellent. Permethrin is a synthetic pyrethroid insecticide and
      repellent. Used in conjunction with proper clothing and other personal protective
      equipment, these repellents provide the best known protection available and are
      critical in minimizing the occupational health threat of arthropod-borne diseases
      to troops in the field.

PMID- 9597851
TI  - Psychological characteristics of wounded and disabled Croatian war veterans.
AB  - OBJECTIVE: Evaluation of the psychological state of a group of 119 Croatian
      disabled war veterans who suffered grave traumatic war experiences during the war
      in Croatia (1991-1992). METHODS: Semistructured Clinical Interview, Profile Index
      Emotions test, and Zung's Self-Rating Depression Scale were used to assess
      disabled war veterans accommodated in special institutions for rehabilitation.
      RESULTS: Changes in psychological functioning were established in 63.8% of
      disabled war veterans, the most frequent among them being indisposition,
      irritability, anxiety, and fear. In nearly half of the veterans there were
      changes in their relationships with close persons, difficulties in accepting the
      reality of their situations, and increased aggressiveness. Higher average values
      on the depression index (0.52) were also established. CONCLUSION: The established
      change in the psychological profile of disabled Croatian war veterans was lower
      than expected. However, because of their great vulnerability, it is necessary to
      increase efforts to secure their complete psychosocial recovery.

PMID- 9597852
TI  - Acute necrotizing ulcerative gingivitis-periodontitis: a literature review.
AB  - Acute necrotizing ulcerative gingivitis-periodontitis (ANUG/NUP) is a relatively
      uncommon periodontal disease characterized by gingival necrosis and ulceration,
      pain, and bleeding. The purpose of this paper is to provide a review of current
      knowledge on ANUG/NUP. Current literature on the epidemiology, pathogenesis,
      immunology, predisposing factors, and treatment of ANUG/NUP is reviewed.

PMID- 9597853
TI  - Inhalation of volatile substances: an emerging threat to readiness?
AB  - Volatile substance abuse is the deliberate inhalation of volatile substances to
      achieve intoxication. We discuss the history and pathophysiological effects of
      commonly abused volatile substances. We explore three deaths and one serious
      accident in active duty military settings. The causes for abuse in the military
      environment are numerous and include remote duty, peer influence, low cost, rapid
      onset, limitation of ethanol use, difficult detection/screening for use, and lack
      of knowledge among users and authorities. The lethality of these substances and
      their casual use can constitute a threat to military readiness. Our experience
      suggests an increase in the use of these substances in the military paralleling
      their increasing use in the general population. Education and awareness training
      could limit fatalities and decrease the threat in military and civilian
      populations.

PMID- 9597854
TI  - High-velocity gunshot wounds to the head and neck: a review of wound ballistics.
AB  - Patients who sustain gunshot injuries to the head and neck face heavy tissue
      damage and eventually life-threatening conditions. A very significant factor that
      determines the degree of injury is the course and extent of the missile track.
      The missile track is well correlated with bullet structure, size, and velocity,
      which have distinct features in civilian and military firearm injuries. The
      missile entrance or exist wound may be out of sight in some injuries, and often
      it is difficult to predict the severity of the injury in the chaotic
      circumstances of the battlefield. We studied the wound ballistics in five
      soldiers who suffered penetrating cranial and cervical firearm injuries.

PMID- 9597855
TI  - Outcome after external decompression for massive cerebral infarction.
AB  - Acute ischemic stroke involving the entire vascular distribution of a carotid or
      middle cerebral artery can cause massive cerebral edema. This study evaluated
      external decompression for the treatment of massive stroke and analyzed possible
      prognostic factors. Twenty-four patients with acute massive cerebral infarction,
      which had progressed to tentorial herniation and impending death, underwent
      external decompression after medical therapy failed to achieve an effective
      response. The neurological outcome 2 months after surgery using the Glasgow
      Outcome Scale was severe disability in 14 patients, vegetative state in two, and
      death in eight. The overall mortality was 33%. Various characteristics (age, sex,
      etiology, side of hemispheric infarction, pupillary asymmetry, Japan Coma Scale,
      distribution of infarction, hemorrhagic infarction, midline shift, tentorial
      herniation) were evaluated to determine the factors associated with high
      mortality after surgical intervention. There was no statistically significant
      relationship between any variable and mortality. Mortality was especially high in
      the patients with preoperative consciousness level of 200, anterior, middle, and
      posterior cerebral artery territory infarction, and stage III of tentorial
      herniation. Postoperatively, all patients with severe disability returned to a
      clear level of consciousness. Six patients with dominant hemisphere stroke had
      some measure of communicative skills in spite of aphasia. External decompression
      is a life-saving treatment for patients with massive cerebral infarction and can
      provide a reasonable quality of life even for those with dominant hemisphere
      strokes. Decompressive surgery should be considered and performed as soon as
      possible if computed tomography demonstrates signs of descending tentorial
      herniation.

PMID- 9597856
TI  - Effects of dobutamine on brain surface microvessels in rats.
AB  - The effects of dobutamine on the diameters of rat pial vessels were investigated
      in vivo using a closed cranial window technique. Dobutamine (10(-7)-10(-3) M) was
      dissolved in artificial cerebrospinal fluid (CSF). Arterioles (17-78 microns in
      diameter) and venules (20-97 microns in diameter) were observed through the
      cranial window over the left parietal cortex. Superfusion of the brain surface
      with only artificial CSF had no effect on vessel diameter. Dobutamine, even at a
      high concentration of 10(-4) M, did not induce significant diameter changes in
      the pial vessels, compared with control animals. The arterioles showed marked
      dilatation (+73%) during superfusion with 10(-3) M dobutamine (p < 0.01 vs.
      control). The venules were also dilated (+12%), although the increased diameter
      was not statistically different from controls. Therefore, dobutamine did not
      induce a dose-dependent dilation. The results strongly suggest that dobutamine at
      clinical dosages does not have a direct vasomotor effect on brain microvessels.

PMID- 9597857
TI  - Embolization of cerebral aneurysms using Guglielmi detachable coils--problems and
      treatment plans in the acute stage after subarachnoid hemorrhage and long-term
      efficiency.
AB  - This study investigated the problems in treating ruptured aneurysms using
      Guglielmi detachable coils (GDCs) in the acute stage and evaluated the long-term
      efficacy in a series of 25 patients with 29 aneurysms. Eight patients with
      ruptured aneurysm treated within 2 weeks of the onset of subarachnoid hemorrhage
      (SAH) suffered no mortality or morbidity related to the procedure. Five patients
      achieved good outcomes despite severe SAH and returned to their previous lives.
      Three patients had poor clinical outcomes, two related to vasospasm and one
      related to pulmonary complication. More than 9 months follow-up was completed in
      14 patients with 16 aneurysms. All six small aneurysms with small necks were
      completely obliterated and no recanalization was seen, and two of the eight large
      or giant aneurysms were completely obliterated. Recanalization was seen in four
      large or giant aneurysms and one small aneurysm due to coil compaction within 13
      months. One patient died of rupture of a large aneurysm 18 months after complete
      obliteration of the aneurysm. Embolization using GDCs in the acute stage after
      SAH can prevent rerupture of cerebral aneurysms. However, recanalization due to
      coil compaction was the major problem in the chronic stage. Intensive follow-up
      and additional embolization, if necessary, is important.

PMID- 9597858
TI  - Threaded fusion cage for lumbar spondylolisthesis.
AB  - Fifteen patients with Meyerding I spondylolisthesis causing disabling lumbago
      underwent threaded fusion cage implantation at the unstable segments. Low back
      pain and intermittent claudication subsided in all patients postoperatively. The
      preoperative Japan Orthopaedic Association score was 11.5 on average, and
      improved to 23.5 after surgery. Five patients achieved significant resolution of
      preoperative symptoms, six improved reasonably, and four required less
      medication. There was no failure of fixation. No patient required supplemental
      fixation such as pedicle screws to achieve stable fusion. One patient had an
      inflammatory course but re-surgery was not necessary. The threaded fusion cage is
      an effective and promising device for the relief of low back pain when used to
      promote fusion of the lumbar spine in patients with low-grade spondylolisthesis.

PMID- 9597859
TI  - Magnetic resonance imaging features of unusually dilated Virchow-Robin spaces-
      two case reports.
AB  - Two patients presented with unusually dilated Virchow-Robin spaces appearing as
      cystic lesions of varying size with signal intensity identical to the
      cerebrospinal fluid on all magnetic resonance pulse sequences. However, fluid
      attenuated inversion-recovery (FLAIR) images disclosed small, high intensity foci
      adjacent to these cystic lesions in one patient. These high intensity foci on
      FLAIR images may represent chronic ischemic change, which produces the gradual
      dilation of the Virchow-Robin spaces.

PMID- 9597860
TI  - Hypoglossal nerve paresis caused by spontaneous dissection of kinked internal
      carotid artery--case report.
AB  - A 54-year-old male presented with pure hypoglossal nerve paresis. Angiography and
      magnetic resonance (MR) imaging showed the characteristic findings of left
      internal carotid artery (ICA) dissection. He received aspirin and his symptoms
      gradually disappeared. Repeat angiography and MR imaging showed that the lesion
      had completely disappeared. This case supports the hypothesis that hypoglossal
      nerve paresis is due to nerve stretching and compression by intramural hematoma
      of the dissected ipsilateral ICA, and severe tortuosity of the ICA may be a
      related phenomenon.

PMID- 9597862
TI  - Irrigation system equipped on a high-speed air drill--technical note.
AB  - An irrigation system which can easily be applied to the conventional high-speed
      air drill was developed to allow simultaneous irrigation during micro-drilling.
      The irrigation system is constructed with a tube of 0.8 mm outer diameter and
      supporting rings. Irrigation is entirely coordinated with drilling by a single
      foot switch. The tube of the system ejects normal saline intermittently toward
      the cutter bar tip. Use of this system in skull base surgery showed that
      effective irrigation and a clean operative field was achieved even in a narrow
      space under the operating microscope, saline is ejected exactly on the point of
      drilling and over-heating does not occur so that heat-related damage to the local
      nerves and blood vessels is avoided. The system can easily be applied to any type
      of high-speed air drill by using supporting rings of the correct size. This
      irrigation system is particularly useful in microneurosurgery using the high
      speed air drill.

PMID- 9597861
TI  - Symptomatic spinal arachnoid cyst triggered by seat belt injury--case report.
AB  - A 49-year-old male presented with a symptomatic thoracic intradural arachnoid
      cyst triggered by seat belt trauma, which appeared within 3 weeks following a
      traffic accident. The initial symptom was a dull back pain induced immediately
      after the accident. Three and half months later, magnetic resonance (MR) imaging
      diagnosed the cystic nature of the lesion consistent with a low intensity on T1
      weighted image which extended dorsally between the T-4 and T-6 levels. One month
      later, MR imaging showed that this cystic mass had enlarged in the
      anteroposterior direction associated with developing clinical symptoms. The final
      diagnosis of arachnoid cyst was made based on surgical findings and histological
      examinations. The spinal arachnoid cyst was probably a congenital arachnoid cyst
      or diverticula originating from the septum posticum which became enlarged due to
      sudden increase of intra-abdominal pressure caused by the fastened seat belt
      during the accident.

PMID- 9597863
TI  - [Antimicrobial prophylaxis in transurethral resection of the prostate].
AB  - OBJECTIVE: A prospective trial was performed to propose a suitable antimicrobial
      prophylaxis in patients undergoing transurethral resection of the prostate (TUR
      P). SUBJECTS AND METHODS: Patients who underwent TUR-P due to symptomatic
      prostatic hyperplasia between April 1995 and February 1996 were included. Based
      on the results of urinalysis obtained within preoperative 3 days, the patients
      were classified into Group I (less than 5 WBC/hpf and bacterial count of less
      than 10(4) CFU/ml in urine specimen), and Group II (5 or more WBC/hpf or
      bacterial count of 10(4) or more CFU/ml in urine specimen). Furthermore, each
      group was randomly subdivided into Group A and Group B according to the period of
      antimicrobial administration. As prophylactic antimicrobials, cefazolin (CEZ) was
      used in Group I and CEZ or cefotiam (CTM) in Group II. The antimicrobial was
      administered only on the day of operation in Group IA (n = 92), for 3 days in
      Group IB (n = 96), 2 days in Group IIA (n = 37), and 4 days in Group IIB (n =
      30). On the day of operation, the antimicrobial was infused immediately before
      the operation. The presence or absence of pyuria, bacteriuria and febrile
      infection, and the period required for normalization of the urinalysis were the
      major points evaluated here. RESULTS: No significant differences were observed in
      any parameters with respect to the period of administration of antimicrobial
      between the groups, but in both Group I and Group II, the incidence of febrile
      infection was higher in the groups with shorter antimicrobial administration
      periods. The mean period for normalization of the urinalysis required 68.4, 68.6,
      65.2 and 58.2 days in Group IA, Group IB, Group IIA and Group IIB, respectively.
      CONCLUSION: It is concluded that 3 or 4-day administration of first or second
      generation parenteral cephems is generally acceptable regimen for antimicrobial
      prophylaxis in patients undergoing TUR-P.

PMID- 9597865
TI  - [Ultrasonographic screening in healthy 3-month-old children for congenital
      malformations of the urinary tract].
AB  - BACKGROUND AND METHODS: We performed renal ultrasonographic screening on 3799
      healthy 3-month-old infants, who showed up for the routine health check up in
      Nobeoka City, for congenital malformations of the urinary tract. RESULTS: Urinary
      tract disorders were suspected in 139 (3.7%). Almost all ultrasonographic
      abnormalities of these were dissociation of CEC (Central Echo Complex). Thirty
      three (24.4%) of the 135, which was 0.9% of the original 3799, were diagnosed as
      having significant congenital anomalies in urinary tract, such as vesicoureteral
      reflux (VUR) in 17, hydronephrosis in 10, unilateral renal agenesis in 2,
      unilateral small kidney in 2 and each case of horseshoe kidney, simple
      ureterocele, ectopic ureterocele, megaureter and mild dilated ureter. Minor or
      mild renal pelvis enlargement without the dilatation of calyx was found in 78
      cases. Fifty-three of the 78 were followed more than 3 months, and complete or
      partial reduction of the pelvic enlargement was noted in 39 (74%), while enlarged
      pelvis remained unchanged in 14. There was no progressive hydronephrosis among
      these patients during the follow-up. Urinary tract infections were found in 6
      cases (5 in VUR and 1 in ectopic ureterocele). Eleven ureters in 9 children of
      VUR (44%) were cured spontaneously (follow-up period: 3 months-6 months and 2
      years). Surgical correction was required in 6 cases, antireflux surgery for VUR
      in 4, heminephroureterectomy for ectopic ureterocele in 1 and endoscopic incision
      of ureterocele for simple ureterocele in 1. CONCLUSION: Our result indicate that
      infant ultrasonographic screening is a useful and valuable method of detecting
      urinary tract malformations.

PMID- 9597864
TI  - [The intrarenal distribution of prostaglandin E2 and thromboxane A2 in the rat
      with unilateral ureteral obstruction or unilateral nephrectomy].
AB  - BACKGROUND: We evaluated the intrarenal distribution of prostaglandin E2 (PGE2)
      and thromboxane B2 (TxB2) on the rats that underwent unilateral ureteral
      obstruction (UUO), unilateral nephrectomy (UNX) or sham operation. METHODS: Male
      Sprague-Dawley rats were divided into three groups; left ureteral obstruction
      (UUO), left nephrectomy (UNX) and sham-operation (Control). They were sacrificed
      at 1, 3, 6, 12, 24 hours and Day 2, Day 3, Day 5, Day 7 and Day 9 after surgery.
      Intrarenal distribution of eicosanoids were immunohistochemically detected on
      both kidneys of UUO rats, and on right kidneys of UNX and Control rats. RESULTS:
      PGE2: In the obstructed kidneys, immunostained PGE2 increased in medullary
      interstitium at one hour to 6 hours, and in glomeruli and cortical interstitium
      at 6 hours. An increase of immunostained PGE2 was observed again in cortical
      interstitium at Day 3 to 5, and in medullary interstitium at Day 2 to 5. In the
      intact opposite kidneys, expression of immunostained PGE2 increased in glomeruli
      at Day 5 to 7, and in medullary interstitium at Day 3 to 5. In UNX, immunostained
      PGE2 increased in the medullary interstitium of the remnant kidneys at 3 hours
      and Day 3 to 7. On the other hand, an increase of immunostained PGE2 observed in
      glomeruli and cortical interstitium of these kidneys at Day 5 to 7. TxB2: In the
      obstructed kidneys, immunostained TxB2 increased in glomeruli and cortical
      interstitium at 6 hours, and in medullary interstitium at 3 to 12 hours.
      Predominant expression of TxB2 was observed in medullary interstitium at 3 hours
      compared to PGE2. We also observed an increase of immunostained TxB2 in cortical
      interstitium at Day 3 to 5, and in medullary interstitium at Day 2 to 5. In the
      intact opposite kidneys, immunostained TxB2 increased in medullary interstitium
      at 3 hours and Day 3. In the remnant kidneys of UNX, an increase of immunostained
      TxB2 was demonstrated in glomeruli at 6 hours and Day 7, and in medullary
      interstitium at 3 to 6 hours and Day 3 to 7. CONCLUSION: In the obstructed
      kidneys, imbalance between PGE2 and TxA2 may contribute to the progression of
      renal injuries. The fact that expression patterns of these eicosanoids in the
      opposite kidneys of UUO different from that of the remnant kidneys of UNK, even
      though both were similarly associated with functional loss of contralateral
      kidneys, suggested that the opposite kidneys of UUO were affected by any
      additional factors different from that responsible for the remnant kidneys of
      UNK.

PMID- 9597866
TI  - [Studies on infection urolithiasis--urease induced crystallization in synthetic
      urine].
AB  - BACKGROUND: In the present study, urease induced crystallization in synthetic
      urine was studied by an aggregometer technique. MATERIALS AND METHODS: The
      synthetic urine was made by the method by Griffith et al (1976). The synthetic
      urine of 200 microliters portions were stirred constantly at 37 degrees C, and
      then 10 microliters of urease solution (1000 U/ml) was added. An aggregometer
      were recorded as turbidity curves on a chart during the incubation for the
      crystallization simultaneously. RESULTS: A two-phase turbidity curve was obtained
      from the reaction of synthetic urine and urease. Firstly the mild turbidity
      appeared gradually up until to approximately 13 min, and then the turbidity
      increased rapidly. The mild turbidity was called "early crystallization" and the
      rapid turbidity was called "late crystallization". The early crystallization
      appeared gradually at pH 7.3 and 0.05 M of anmmonia concentration, and this
      amount was completely depended on the concentration of calcium in the synthetic
      urine. The late crystallization occurred rapidly at pH 8.5 and 0.06-0.08 M of
      anmmonia concentration and this amount was completely depended on the
      concentration of magnesium in the synthetic urine. We confirmed the early
      crystallization as calcium phosphate and the late crystallization as magnesium
      ammonium phosphate by the observations of polarized light microscopy as well as
      the estimations using an infrared spectrometer. CONCLUSION: Urease induced
      crystallizations in the synthetic urine had a two-phase turbidity. Firstly the
      mild turbidity of calcium phosphate appeared gradually, and then rapid turbidity
      of magnesium ammonium phosphate occurred. Therefore, it is suggested that various
      crystallizations may be developed in the infected human urine according to the
      constituents of calcium and magnesium.

PMID- 9597867
TI  - [Studies of type I collagen related substances as bone metastatic markers of
      prostate carcinoma with special regard to serum carboxyterminal propeptide of
      type. I. Procollagen (PICP), cross-linked carboxyterminal telopeptide of type I
      collagen (ICTP) and Urinary deoxypyridinoline levels].
AB  - BACKGROUND: To investigate if serum levels of carboxyterminal propeptide of type
      I procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen
      (ICTP) and urinary levels of deoxypyridinoline (D-Pyr) are useful markers of bone
      metastasis in patients with prostate carcinoma, we measured these markers in
      patients with untreated benign prostatic hyperplasia (BPH) and untreated prostate
      carcinoma (PCA). METHODS: Serum PICP, ICTP and urinary D-Pyr levels were
      determined in 53 patients; 16 patients with BPH, 15 patients with PCA without
      bone metastasis (stage A, B, C and D1) and 22 patients with PCA with bone
      metastasis (stage D2). At the same time correlations among these markers and
      serum total alkaline phosphatase (ALP) activity were studied. RESULTS: Serum
      PICP, ICTP and urinary D-Pyr levels in the PCA patients with bone metastasis were
      significantly higher than those of BPH. The serum levels of PICP in patients with
      PCA with bone metastasis group were significantly higher than those of without
      bone metastasis group. The serum levels of ICTP in patients with PCA without bone
      metastasis group were significantly higher than those of BPH group, while no
      significant difference was observed between PCA group with and without bone
      metastasis. In the PCA patients with bone metastasis, serum PICP and serum total
      alkaline phosphatase (ALP) activity were significantly correlated (r = 0.80). In
      these patients, serum ICTP and urinary D-Pyr levels were also significantly
      correlated (r = 0.70). CONCLUSION: These results suggest that serum PIPC, ICTP
      and urinary D-Pyr are the useful markers to quantitate bone metastasis in the
      patients with PCA. Moreover, the determination of serum ICTP levels may be
      significant for detecting occult bone metastasis in the patients with PCA.

PMID- 9597868
TI  - [Establishment and characterization of the SV40-transformed stromal cell line
      from rat dorsolateral prostate].
AB  - BACKGROUND: The SV40-transformed stromal cell line (PSSVH) was established from
      rat dorsolateral prostate. To clarify the usefulness, PSSVH was studied on the
      immunohistochemical characteristics and the mRNA expression of growth factors and
      their receptors. METHOD: Immunohistochemical method was used to detect
      cytokeratin, vimentin and large T antigen in the PSSVH cells. Chromosomal
      analyses were carried out by the Giemsa-banding technique. [3H]-thymidine uptake
      method was used to examine the influence for cell proliferation of androgens. To
      examine the expression of mRNA for epidermal growth factor (EGF), basic
      fibroblast growth factor (bFGF), keratinocyte growth factor (KGF), transforming
      growth factor (TGF)-alpha, TGF-beta 1 and their receptors, poly (A) RNA was
      extracted from PSSVH cells and Northern blot analysis was done. RESULT:
      Immunohistochemically, PSSVH was positive for large T antigen, and the cell had a
      character of stromal cell which included a negative result for cytokeratin and a
      positive for vimentin. The cell had a karyotype of aneuploid, whereas it had not
      a common marker chromosome. The addition of testosterone (T: 10(-10)-10(-6) M)
      and 5 alpha-dihydrotestosterone (DHT: 10(-10)-10(-6) M) did not influence on the
      DNA synthesis of PSSVH cells. Northern blot analysis showed expression of mRNA
      for KGF, TGF-alpha, TGF-beta 1, EGF receptor and TGF-beta receptor (type II) in
      PSSVH cells. These expressions were not influenced by the addition of androgens.
      CONCLUSION: PSSVH is the androgen-independent stromal cell from rat dorsolateral
      prostate and may be useful for the fundamental study of the prostate.

PMID- 9597869
TI  - [A case of pyelitis cystica diagnosed with utilization of ureterofiberscope].
AB  - We herein report a case of pyelitis cystica in 65-year-old woman. She was
      referred to our hospital in order to have a treatment for a stone in the ureter
      on left side. Excretory urogram showed hydronephrosis on left, and multiple,
      small, smooth and round filling defects in the renal pelvis on right side. ESWL
      was performed to the ureteral stone, and the stone was discharged completely in 4
      days. Then further examinations were made for the filling defects of right renal
      pelvis. Nonopaque calculi were ruled out on retrograde pyelogram and CT scan.
      Urinary cytology from the renal pelvis was class I. Our impression was pyelitis
      cystica of right kidney. Under spinal anesthesia, ureterofiberscopy was
      performed. Multiple small cysts were observed in the pelvis and calyx, as well as
      cystitis cystica. Cold cup biopsy was also done and histopathological finding ws
      pyelitis cystica, without malignancy. We compared endoscopic findings with
      radiographic findings in 18 cases of pyloureteritis cystica from the Japanese
      literature. The radiographic findings were multiple small, in a uniform size, and
      round filling defects with regular contour, and the endoscopic findings were
      multiple white or ocher colored, half sphere or sphere shaped, and small cyst
      with smooth surface in 15 of 18 cases. We thought these findings were
      characteristic ones in pyloureteritis cystica. Endoscopy and biopsy are mandatory
      for diagnosis of pyeloureteritis cystica.

PMID- 9597870
TI  - [Fibroepithelial polyp of the renal pelvis. A case report].
AB  - Benign tumors of the renal pelvis are relatively rare, and only a few reports
      have been published so far. Recently we experienced a case of a 50-year-old woman
      with a fibroepithelial polyp in the left pelvis. Drip infusion pyelography and
      abdominal CT revealed a filling defect and tiny renal stones in the left pelvis
      under the study of her urinary blood occult. A transitional cell carcinoma of the
      renal pelvis was suspected, so a left total nephroureterectomy was done. The
      pathological diagnosis of this tumor was fibroepithelial polyp. As it is said
      that preoperative diagnosis of such a polyp is difficult, preoperative
      ureteroscopy or perioperative pathological diagnosis by frozen sections should be
      attempted. But it is difficult to avoid a nephroureterectomy because low
      incidence of the disease.

PMID- 9597871
TI  - [The Leydig cell tumor and combined germ cell tumor in the unilateral testis. A
      case report].
AB  - The simultaneous occurrence of germ cell tumors and stromal tumor in the
      unilateral testis is extremely rare. We report a case of Leydig cell tumor and
      combined germ cell tumor in the right testis on a 24-year-old man. Histopathology
      revealed seminoma, embryonal carcinoma, choriocarcinoma and Leydig cell tumor.

PMID- 9597872
TI  - [Recent advances in Alzheimer research].

PMID- 9597873
TI  - [Mitochondrial DNA and aging].

PMID- 9597874
TI  - [Progress of gerontology in Japan].

PMID- 9597875
TI  - [History of International Association of Gerontology (IAG)].

PMID- 9597876
TI  - [Life style to prevent aging].

PMID- 9597877
TI  - [The life style for prevention of the geriatric diseases].

PMID- 9597878
TI  - [Masticatory function and life style in aged].
AB  - Elderly people gain enjoyment in their remaining years from eating, speaking and
      tasting things, and they find that the oral function is necessary to arouse in
      them a desire to work for society, in addition to looking after their own health,
      they find that over function is important. Recently, more attention has come to
      be paid to one's external appearance. Even if function is impaired, appearance
      has a strong influence on the feeling of leading a worth-while life. Though
      increasing age brings a steady loss of teeth, it is unlikely that physiological
      change resulting from tooth decay and disease are the cause of tooth loss.
      Degradation of the hard tissue caused by decay is unavoidable. Unless the decayed
      area is removed and the teeth are repaired with artificial materials, the
      function of the affected tooth is permanently lost. Moreover, as decay progresses
      and periodontal disease worsens the state of a given area, extraction becomes
      necessary. This is the process by which teeth are lost. However, even if teeth
      are lost, masticatory function may be restored through the use of dentures.
      Recently, we carried out a survey which showed that a group of elderly people
      with good masticatory functions were more healthy and lived longer than a group
      of elderly people with reduced physical functions (weight, grasping strength,
      balance, bone salt volume) and poor masticatory function.

PMID- 9597879
TI  - [Relation between atherosclerotic risk factors and abdominal wall fat thickness].
AB  - We used ultrasonography to assess the accumulation of visceral fat and its
      relation to known risk factors for atherosclerotic disease, and examined its
      relation with atherotic changes in the common carotid artery. The subjects were
      315 consecutive inpatients (173 men, 142 women; mean age, 68.3 years)
      hospitalized during a 21-month period. Those with a history of epigastric surgery
      or nutrition disorders that might affect fat thickness were excluded. A 7.5-MHz
      transducer was used to evaluate the maximum thickness of preperitoneal fat (Pmax)
      at the anterior surface of the liver, and the minimum thickness of subcutaneous
      fat (Smin) of the abdomen. The fat/height ratio was calculated. Age, gender,
      smoking status, blood pressure, total cholesterol, triglyceride, HDL-cholesterol,
      LDL-cholesterol, atherogenic index ((total cholesterol-HDL-cholesterol)/HDL
      cholesterol), blood sugar, serum insulin, and uric acid were examined as
      confounders. Pmax/height was found to be related to systolic blood pressure,
      diastolic blood pressure, total cholesterol, triglyceride, HDL-cholesterol, LDL
      cholesterol and atherogenic index, and was positively associated with the
      thickness of the common carotid arterial wall. Pmax/height may be a useful means
      to evaluate known risk factors for atherosclerotic disease.

PMID- 9597880
TI  - [Significance of pontine high signal intensity lesions on magnetic resonance
      imaging in patients with cerebral infarction].
AB  - We reviewed MRI findings in a series of 211 patients with cerebral infarction. A
      high signal in the basis pontis bilaterally in T2 weighted images (Central
      Pontine Hyperintensity, CPH), with almost-normal T1 weighted images, was present
      in 29 cases (12.9%). CPH findings were present more frequently in elderly
      patients, and were significantly associated with a previous history of
      cerebrovascular accident, although not with other arteriosclerotic risk factors.
      In patients with CPH. periventricular hyperintensity was severe and the number of
      infarctions of the thalamus was higher. These results suggest that a) CPH may
      arise from ischemia in subcortical areas or in the territory of the
      vertebrobasilar system, and that b) chronic brain ischemia, which may be
      partially due to aging, may play a more important role in cerebral infarction
      than the usual arteriosclerotic risk factors.

PMID- 9597881
TI  - [Assessment of exercise-induced silent myocardial ischemia by dipyridamole
      thallium imaging: (1). Its significance in stable angina pectoris].
AB  - To assess the clinical significance of silent myocardial ischemia (SMI) in the
      elderly, 113 patients with stable angina who showed ischemic ST depression during
      treadmill stress testing were studied by dipyrimadole thallium imaging and
      coronary arteriography. They were divided into two groups: 44 patients with
      silent ST depressions and 69 patients with painful ST depressions. The groups
      were compared for scintigraphic and coronary arteriographic features as well as
      prognosis. There was a significantly greater proportion of older patients (> or =
      65 years) in the group with SMI (64%) than in the group with painful ischemia
      (38%) (p < 0.01), although there was no difference in the mean ages of the two
      groups. The prevalence of multivessel coronary stenosis was not significantly
      different between the two groups (45% in the SMI group and 61% in the group with
      painful ischemia). Treadmill stress testing showed no differences in exercise
      duration, maximal heart rate, maximal systolic blood pressure, or maximal ST
      depression between the two groups. Dipyrimadamole thallium imaging revealed
      similar results in the site of reversible defects (RD), i.e. 76% in the anterior
      area and 24% in the inferior area in patients with SMI, and 83% in the anterior
      area and 17% in the inferior area in patients with painful ischemia. However, the
      size of RD was significantly smaller in patients with SMI, i.e. 14.6 +/- 6.1
      segments in patients with SMI and 18.7 +/- 8.3 segments in patients with painful
      ischemia (p < 0.05). Although a significantly higher proportion of patients with
      painful ischemia (48%) underwent PTCA or CABG as their initial therapy as
      compared to those with SMI (16%), there was no significant difference in the
      cardiac event rate between the two groups initially treated medically. Among
      patients with stable angina, those with SMI may have a smaller amount of ischemic
      myocardium and may be older in a greater proportion than those with painful
      ischemia. Dipyrimadole thallium imaging is useful in the assessment of SMI in the
      elderly.

PMID- 9597882
TI  - [Assessment of exercise-induced silent myocardial ischemia by dipyridamole
      thallium imaging. (2). Its significance in Q wave myocardial infarction].
AB  - The clinical significance of silent myocardial ischemia (SMI) in the elderly was
      assessed in 91 patients with Q wave infarction who showed ischemic ST depression
      during treadmill stress testing, as well as reversible defect (RD) during
      dipyridamole thallium imaging. They were divided into two groups (47 patients
      with silent ST depression and 44 patients with painful ST depression) and
      compared for scintigraphic and coronary arteriographic features, and prognosis.
      There was no significant difference in age, gender and site of infarction between
      the two groups. The prevalence of single and double vessel coronary stenosis was
      higher in patients with SMI (66%) than in those with painful ischemia (p < 0.05).
      The results of treadmill stress testing showed a longer exercise duration (4.7 +/
      1.7 vs. 4.1 +/- 1.8 min) and higher maximal heart rate (138 +/- 15/vs. 126 +/-
      20/min) in patients with SMI than in those with painful ischemia (p < 0.01).
      Dipyridamole thallium imaging revealed a larger infact (18.8 +/- 9.1 vs. 14.6 +/-
      10.2 segments) in patients with SMI than in those with painful ischemia (p <
      0.05). The prevalence of RD in the area of infarction was also higher in patients
      with SMI (74%) than in those with painful ischemia (45%) (p < 0.05). Although a
      higher proportion of the patients with painful ischemia (42%) underwent CABG or
      PTCA as their initial therapy, compared with those with SMI (25%) (ns), there was
      no difference in the cardiac event rate between the two groups who were initially
      treated medically. Dipyridamole thallium imaging is useful in the assessment of
      SMI in elderly patients with Q wave myocardial infarction. Those with SMI may
      have a larger infarct and a higher prevalence of ischemia localized within the
      infarction than those with painful ischemia.

PMID- 9597883
TI  - [Three patients with insulin-treated diabetes and senile dementia of Alzheimer's
      type].
AB  - Senile dementia of Alzheimer's type (SDAT) is reported to be less frequent in
      patients with Diabetes Mellitus. However the, the number of elderly people in
      still increasing in Japan, an is the incidence of diabetes mellitus, especially
      in middle-aged and elderly people. Thus, we can expect to encounter more elderly
      people with diabetes and SDAT. We encountered three patients with diabetes who
      were treated with insulin and in whom SDAT developed. In all three, control of
      blood glucose levels gradually worsened, despite increases in the dose of
      injected insulin. It was later found that they did not inject insulin properly
      because of SDAT. They lived alone and their dementia was not diagnosed before
      their admission to the hospital. In its early phase, SDAT can be difficult to
      diagnose, especially in patients who live alone. SDAT should be considered when
      the control of blood glucose levels for no apparent reason in elderly patients
      with diabetes.

PMID- 9597884
TI  - [Clinical picture of autoimmune hemolytic anemia].

PMID- 9597885
TI  - [The concept of REAL classification, a new classification of human malignant
      lymphomas].

PMID- 9597886
TI  - [WHO Classification Project on Neoplastic Diseases of the Hematopoietic and
      Lymphoid Tissues and its relation to REAL classification].

PMID- 9597887
TI  - [A clinical application of the revised European-American Lymphoma Classification
      for Prognostic and Therapeutic Purpose].

PMID- 9597888
TI  - [Malignant lymphoma in Japanese based on REAL classification].

PMID- 9597889
TI  - ["Indolent B-cell lymphoma" based on the histologic review according to REAL
      classification].

PMID- 9597890
TI  - [An evaluation of diffuse large B-cell lymphoma according to the REAL
      classification].

PMID- 9597891
TI  - [Clinical significance of the distinction of CD56 positive angiocentric lymphoma
      by REAL classification].

PMID- 9597892
TI  - [TAL1 gene analysis in T-cell malignancies].
AB  - Site-specific recombination of the TAL1 gene was analyzed by Southern blotting
      and polymerase chain reaction (PCR) in 44 cases of childhood T-cell acute
      lymphoblastic leukemia (T-ALL), 20 cases of childhood T-cell non-Hodgkin's
      lymphoma (T-NHL) and 35 cases of adult T-cell malignancies. This recombination
      was found in 10 (22.7%) of 44 childhood T-ALL patients, but in none of the T-NHL
      or adult T-cell malignancies. Recombination of the TAL1 gene was therefore
      suggested to be specific for childhood T-ALL. The immunophenotypic features of
      the 10 T-ALL patients with this recombination were CD1-, CD2+, CD4-, CD7+, CD10-,
      and they had a significantly better outcome than other T-ALL cases without the
      recombination. The PCR technique revealed minimal residual disease (MRD) in 2
      patients. One showed persistent MRD, while in the other MRD was recognized only
      at initial diagnosis. Further investigation is needed whether T-ALL with this
      recombination constitutes a distinct clinical subgroup among childhood T-ALL
      patients.

PMID- 9597893
TI  - [EPOCH therapy for relapsed/refractory lymphoid malignancies].
AB  - Patients with refractory or relapsed non-Hodgkin's lymphoma (NHL), acute T-cell
      leukemia (ATL), ATL lymphoma and acute lymphocytic leukemia (ALL) received EPOCH
      therapy. All were previously treated with doxorubicin (DOX), vincristine (VCR)
      and other drugs. The EPOCH treatment schedule is consisted with DOX (10
      mg/M2/day, 5 days c.i.v.), VCR (0.4 mg/M2/day, 4 days c.i.v.), etoposide (50
      mg/M2/day, 4 days c.i.v.), cyclophosphamide (750 mg/M2/day, day 6 i.v.) and
      prednisolone (60 mg/M2/day, 5 days p.o.). Twenty-one patients (ALL:10, NHL:8,
      ATLL:2, ATL:1) were assessable for response and toxicity. Two patients with ALL
      and NHL, respectively, achieved a complete remission and 3 patients obtained
      partial remission (NHL:2, ATLL:1). The hematological toxicity (grade > 1)
      included neutoropenia, anemia and thrombocytopenia, which were observed in 83.3%,
      76.7% and 76.7% respectively, of total 30 EPOCH courses. The major non
      hematological toxicities were nausea/vomiting, constipation and infection, but
      most of the toxicity were tolerable with sufficient clinical supportive care.
      These results indicate that continuous infusion of DOX, VCR and ETP might be
      effective in patients who were treated with, and presumed to be resistant to the
      same drugs administrated by bolus infusion.

PMID- 9597894
TI  - [Serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross
      linked carboxyterminal telopeptide region of type I collagen (ICTP) and
      carboxyterminal parathyroid hormone-related protein (C-PTHrP) in hematological
      malignancies with bone lesions and hypercalcemia].
AB  - We measured the levels of carboxyterminal propeptide of type I procollagen
      (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP)
      and carboxyterminal parothyroid hormone-related protein (C-PTHrP) in serum of
      patients with hematological malignancies. ICTP and C-PTHrP levels in serum of
      multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and adult T-cell leukemia
      (ATL) patients with bone lesions and hypercalcemia were significantly higher than
      those of patients without bone lesions and hypercalcemia. ICTP and C-PTHrP levels
      in ATL were significantly higher than in MM and NHL. There was a correlation
      between ICTP and C-PTHrP in serum of ATL patients, but no correlation in MM and
      NHL. Serum ICTP levels tended to correlate with serum beta 2-microglobulin and
      survival in patients with MM. Therefore, ICTP and C-PTHrP levels in serum may be
      useful in the diagnosis of bone lesions and hypercalcemia in hematological
      malignancies. In particular, ICTP may be a useful bone resorption marker in MM.

PMID- 9597895
TI  - [Treatment of children with non-Hodgkin's lymphoma with CCLSG NHL 855/890
      protocols long-term outcome and incidence of secondary malignancies].
AB  - We report here on treatment results of consecutive CCLSG NHL studies (NHL855,
      1985-1989; NHL890, 1989-1996). The NHL855 protocol consisted of an induction
      phase of five drugs (VCR, PRD, CPM, DXR, and high-dose MTX) and a maintenance
      phase of 7 drugs. The probabilities of EFS at 7 years were 78% (SE, 10%) for the
      patients with localized disease, and 38% (SE, 7%) for those with advanced
      disease. In the NHL 890 protocol, the patients were assigned to two different
      treatment groups according to their histology and received different
      consolidation therapy; non-lymphoblastic subtype was treated almost identically
      to NHL855 while LASP and VP-16 were newly added for the lymphoblastic subtype.
      The 7-year EFS improved to 91% (SE, 6%) for localized disease, and 61% (SE, 6%)
      for advanced disease. A remarkable improvement was particularly evident for
      lymphoblastic type with mediastinal mass. Optional trial of high-dose sequential
      chemotherapy and peripheral blood progenitor cell auto grafting resulted in an
      unfavorable outcome. The 7-year EFS according to main histological subgroups were
      as follows: 84% (10%) for large cell type, 67% (11%) for Burkitt's-type, 58%
      (10%) for lymphoblastic type. Secondary cancer occurred in two of the 163
      patients studied. Both patients were AML (M0/M4) and MLL rearrangement was
      detected in the M4 case.

PMID- 9597896
TI  - [Acquired pure red cell aplasia associated with relapsed non-Hodgkin's lymphoma:
      a case report-improvement of PRCA after acute hepatitis].
AB  - A 47-year-old male patient was admitted because of anemia. He had been diagnosed
      as non-Hodgkin's lymphoma (Follicular mixed, B cell type, stage ISA) by
      splenectomy two years before. Bone marrow examination on admission revealed
      lymphoma cell infiltration and marked decrease in erythroid cells. These findings
      confirmed relapsed lymphoma with acquired pure red cell aplasia. After several
      courses of combination chemotherapy, lymphoma cells disappeared from bone marrow,
      but PRCA was not improved. In this case there were two times remission of PRCA.
      At first time, acute B type hepatitis occurred during the chemotherapy, anemia
      improved transiently. At the second time, mild acute hepatitis associated with
      herpes zoster occurred. Twenty days after hepatic injury, PRCA was improved, and
      continued in remission state till present day. To disclose the mechanism of PRCA
      in this case, erythroid colony assay of marrow cells was performed. This showed
      the presence of inhibitory factor in patient's serum at PRCA state, that was
      considered to be related to the occurrence of PRCA. These findings suggest that
      the improvement of PRCA was associated with the changes on immunological
      condition after acute hepatitis in this case.

PMID- 9597897
TI  - [Primary cardiac non-Hodgkin's lymphoma].
AB  - A 69-year-old man who initially presented with lumbago developed heart failure
      during an MRI scan on the day of admission. A chest X-ray showed cardiomegaly and
      bilateral pleural effusion. Echocardiogram and computed tomography (CT) scan of
      the chest revealed a large tumor mass encompassing the heart with much
      pericardial effusion was demonstrated. The cytology of the effusion obtained by
      pericardiocentesis was consistent with non-Hodgkin's lymphoma, diffuse large B
      cell type. As CT scans of the abdomen and pelvis were negative, he was considered
      to have primary cardiac lymphoma. Although he responded remarkably to therapy
      with vincristine, cyclophosphamide and prednisolone and, he developed acute
      respiratory failure on the seventh month after admission. Although incidence of
      primary cardiac lymphoma is very low, it is necessary to investigate the
      mechanism of this disease in order to establish appropriate diagnostic and
      therapeutic approaches.

PMID- 9597899
TI  - [Hereditary macrothrombocytopenia].
AB  - A 19 year-old male was referred to our department because of
      macrothrombocytopenia. His platelet count was 73,000/microliter and giant
      platelets were observed in the peripheral blood smear specimen. Though he had
      been suffering from severe atopic dermatitis for four years, he seemed to be
      healthy without bleeding tendency. When he underwent a shunt operation for
      tetralogy of Fallot without any complication at nine-years old, thrombocytopenia
      was allegedly pointed out for the first time. Bone marrow aspiration revealed no
      abnormal findings with no chromosomal aberration. Normal platelet aggregation
      responses against adenosine diphosphate, epinephrine, collagen, and ristocetin
      were observed. The platelet adhesiveness (modified Salzman method) was slightly
      elevated. Unlike other reported syndromes associated with macrothrombocytopenia,
      his leukocytes had no inclusion bodies. His mother also had macrothrombocytopenia
      thus, this disorder was suspected to be hereditary.

PMID- 9597898
TI  - [Chronic myelogenous leukemia with long-term hypoplasia induced by alpha
      interferon and hydroxyurea].
AB  - A 48-year-old woman was admitted with chronic myelogenous leukemia in November,
      1996 and was treated with hydroxyurea (HU), because of marked leukocytosis; WBC
      404,000/microliter. On January 29, 1997, administration of HU was stopped, and
      treatment of alpha-interferon (IFN alpha) was started with 6x 10(6)U, every day.
      However, the WBC count rose from 19,600/microliter to 56,800/microliter, and the
      combination of IFN and 2,000 mg of HU was started on February 4. The dose of HU
      was reduced to 500 mg on February 27, and the IFN administration was reduced to 3
      times a week from April 4, because the WBC count was less than 10,000/microliter.
      Pancytopenia was revealed in May. The bone marrow biopsy specimen demonstrated
      marked hypoplastic changes, and chromosome analysis of bone marrow cells showed
      Philadelphia chromosome in all 20 metaphases. Treatment was interrupted for 7
      months, but hematologic parameters did not recover. There were 9 cases reported
      in detail with bone marrow hypoplasia induced by IFN. One patient received IFN
      alone and 8 patients received anti-cancer drugs before treatment of IFN. We
      concluded that great care must be taken for IFN treatment of CML.

PMID- 9597900
TI  - [A combination chemotherapy with cytarabine ocfosfate, low dose etoposide, and G
      CSF for the treatment of high risk MDS (RAEB, RAEBt)--a pilot study].
AB  - We evaluated a combination chemotherapy with cytarabine ocfosfate (SPAC), low
      dose etoposide and G-CSF for the treatment of high-risk MDS (RAEB, RAEBt). Seven
      patients with high-risk MDS were treated with a daily combination, 200 mg/day
      SPAC p.o., 50 mg/day etoposide p.o. and 75 micrograms/day G-CSF s.c. One patient
      achieved complete response, 2 achieved good response and one patient minor
      response. Although all of the patients developed severe marrow hypoplasia after
      chemotherapy, the nonhematologic adverse effects were mild enough to be
      tolerated. This combination chemotherapy should be useful in the clinical
      management of patients with high-risk MDS.

PMID- 9597901
TI  - [Compulsive manipulation of tools in the left hand following damage to the right
      medial frontal lobe].
AB  - In 1982, Mori and Yamadori first reported a woman who showed compulsive
      manipulation of tools (CMT) following an infarction in the left medial frontal
      lobe. When an object was shown, the patient's right hand reached, grasped and
      manipulated it properly against her will. Since then, there have been many
      similar case reports and CMT has been generally believed to occur in the right
      hand after damage to the left medial frontal lobe. However, there also have been
      a few case reports of CMT in the left hand of a patient with damage to the right
      medial frontal lobe. To clarify whether such a patient with CMT in the left hand
      is an exceptional case or not, we prospectively investigated CMT in the left hand
      of 10 patients with an infarction in the right medial hemisphere. All patients
      were examined within 6 weeks after stroke. Magnetic resonance images were used to
      determine the location and extension of a lesion. We found that 7 cases with a
      lesion involving the anterior cingulate gyrus (ACG) and the supplementary motor
      area (SMA) exhibited a grasp reflex and a visual grouping mainly in the left
      hand. Five of these 7 cases had a lesion extending into the middle and anterior
      parts of the ACG and displayed CMT in the left hand. Among those 5 patients, 2
      with a lesion which was extensive enough into the ACG to involve almost entirely
      the anterior part of it adjoining the genu and anterior body of the corpus
      callosum showed a prominent CMT in the left hand. Two patients with a lesion
      principally confined to the SMA showed the grasp reflex and some subvarieties of
      the instinctive grasp reaction mainly in the left hand, but never showed visual
      grouping nor CMT. One patient with a lesion involving the posterior cingulate
      gyrus and medial parietal lobe but sparing both the SMA and ACG showed neither
      grasping responses nor CMT. From these observations, we conclude the following:
      (1) it is not an exceptional case that a right-handed patient with a right medial
      frontal lesion shows CMT in the left hand: and (2) extensive damage to the ACG
      involving its anterior part adjoining the genu and anterior body of the corpus
      callosum is most crucial for the development of CMT.

PMID- 9597902
TI  - [Pain caused by ephaptic transmission occurring in the recovery phase of diabetic
      vascular mononeuropathy was effectively suppressed with L-threo-3,4
      dihydroxyphenyl-serine].
AB  - A 59-year-old man with an 8-years history of diabetes mellitus had an acute onset
      of sharp pain in the anterior part of right lower leg. One month later, the pain
      changed to deep dull nature in the deeper site of the peroneal region. The pain
      increased, when he stood up, walked, and stayed in the cold room and decreased by
      rest. It was more painful in the evening than in the morning. The first sharp
      pain was thought to be caused by ischemia due to diabetic vascular neuropathy.
      The next dull pain was considered to be originated from ephaptic transmission
      between sympathetic efferent fibers to group IV and afferent ones from the
      skeletal muscle. The latter dull pain was selectively suppressed by nerve block
      when it became effective to the branch of deep peroneal nerve to extensor
      digitorum longus muscle. The hypothesis of ephaptic transmission was supported by
      meaningful decrease of muscle sympathetic activity detected by microneurography
      before and after the dosage of L-DOPS, which effectively suppressed the pain as
      well as other alpha-stimulant, midodrine hydrochloride. We concluded that the
      ephaptic pain caused by muscle sympathetic activity could be suppressed by the
      vasoconstrictive drugs through the mechanism of baroreflex control.

PMID- 9597903
TI  - [Cerebral embolism due to left atrial ball thrombus without mitral stenosis-
      usefulness of the transesophageal echocardiography for the diagnosis].
AB  - We reported two cases of cerebral embolism associated with atrial fibrillation.
      Left atrial ball thrombus without mitral stenosis was diagnosed by the
      transesophageal echocardiography, followed by successful removal. Left atrial
      ball thrombus has a risk for lethal complications, and a high incidence of
      systemic embolism even during anticoagulation therapy. An immediate surgical
      treatment is needed. The transthoracic echocardiography is not useful in
      diagnosis for left atrial ball thrombus. It is important to examine left atrial
      ball thrombus by the transesophageal echocardiography in patients with cerebral
      embolism associated with atrial fibrillation.

PMID- 9597904
TI  - [A case of stimulus-sensitive spinal myoclonus].
AB  - A 64-year-old man was admitted to our hospital because of a 2-year progression of
      muscular jerks on the bilateral thoracic and abdominal walls. Neurological
      examination was normal except for myoclonus localized in the bilateral Th5 to L1
      segments. Myoclonus in this case was symmetrical and synchronous, and had a
      tendency to continue rhythmically. It was also segmental and considered to be
      spinal in origin. The interval between two adjacent myoclonic jerks was short
      when the amplitude and duration of the first myoclonus were high and long,
      respectively. We postulated that the activity of anterior horn cells at an
      impaired segment might be a factor that influences the resting time between
      jerks. A myoclonic jerk could be induced by a tendon tap given anywhere on this
      patient's body, with a latency ranging from 40 to 220 msec, irrespective of the
      sites of tapping. A long latency and polysynaptic reflex may participate in such
      stimulus sensitivity. The site of the reflex was probably above the motor nucleus
      of the trigeminal nerve, because jerks could be induced by jaw taps. Our
      observations support the theory that a spino-bulbo-spinal reflex is manifested at
      the impaired segment.

PMID- 9597905
TI  - [A case of eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis
      with unique brain MRI findings].
AB  - A 17-year-old Japanese girl was admitted to our hospital because of meningeal
      irritation, hyperesthesia of extremities, and disturbance of consciousness after
      having traveled to Okinawa in February, 1996. Examination on admission revealed
      pleocytosis of CSF with many eosinophils (65%) and increased eosinophils (25%) in
      the peripheral blood. The history and clinical symptoms were suggestive of a
      parasitic infection. We diagnosed the patient as having eosinophilic
      meningoencephalitis caused by Angiostrongylus cantonensis, which was confirmed by
      immunological tests of double diffusion, counterimmuno-electrophoresis, and
      ELISA. Magnetic resonance imaging (MRI) of the brain demonstrated multiple small
      high intensity areas on Gd-DTPA-enhanced T1-weighted images. MRI findings
      suggested tissue reactions to dead or dying worms, and local vasodilatation
      associated with minimal thrombus formation.

PMID- 9597906
TI  - [A case of fasciitis associated with Basedow's disease and polymyositis].
AB  - A 39-year-old female suffered from diffuse goiter, palpitation, finger tremor and
      body weight loss for about one year. Then she developed acute onset of myalgia
      and swelling of calves, and muscle weakness of proximal limbs. She could not walk
      because of myalgia and muscle weakness, and was admitted to our hospital 4 days
      after the onset of muscle symptoms. On admission, her pulse was 110 per minute
      and she had finger tremor of 11-12 Hz. The thyroid gland was markedly and
      diffusely enlarged with an elastic soft surface. She presented muscle weakness of
      proximal limbs and neck, and had intermittent swelling and myalgia on calves.
      Deep tendon reflexes were increased in all extremities. The erythrocyte
      sedimentation rate was 22 mm per hour. Eosinophilia was not recognized. Serum CK
      level was elevated to 671 IU/l. Serum free T3 was higher than 21.7 pg/ml and free
      T4 was also elevated to 10.19 ng /dl. Serum TSH was lower than 0.05 microU/ml and
      thyroid stimulating antibody was 1,302.0%. Muscle biopsy of her left
      gastrocnemius muscle revealed markedly hypertrophic fascia with inflammatory
      cellular infiltration on HE staining. Inflammatory change was also recognized in
      muscle tissue and in perivascular region of perimysium. Variation of fiber size,
      necrotic fibers, and central nuclei were also seen. From these clinical and
      laboratory findings she was diagnosed as having Basedow's disease associated with
      fasciitis and polymyositis. Her thyroid function was improved by anti-thyroid
      drug, and swelling and myalgia of sural regions and weakness of proximal limbs
      were also improved by steroid therapy. Only one case of Basedow's disease
      associated with fasciitis and seven cases of that associated polymyositis have so
      far been reported. This is the first case report of fasciitis associated with
      Basedow's disease and polymyositis.

PMID- 9597907
TI  - [A case of intracranial tuberculoma followed by MRI].
AB  - A 62-year-old woman with pulmonary tuberculosis was admitted to our hospital. She
      was completely neurologically free at admission and her CSF was normal. Brain MRI
      with Gd-DTPA enhancement demonstrated two mass lesions with ring-enhancement in
      the left temporal lobe and the right frontal lobe. The left temporal lesion had a
      bright central core with hypointense periphery on T2 weighted image. Extended
      hyperintense area was observed around this lesions, which represented brain
      edema. On T1 weighted image, the central core was demonstrated hypointense and
      its periphery was isointense. After starting antituberculous therapy, MRI
      revealed paradoxical expansion of left temporal lesion and neurological symptoms
      worsened temporarily, but, eventually the intracranial lesions diminished in size
      and disappeared, and the symptoms improved. So we diagnosed her as having
      intracranial tuberculoma. By long-term following up with MRI, we observed that
      the central core of the left temporal tuberculoma had changed gradually to
      hypointense on T2 weighted image and hyperintense on T1 weighted image
      respectively. We thought that the change of the central core on MRI represented
      organization of caseated necrosis.

PMID- 9597908
TI  - [Complicated form of spastic paraplegia with congenital cataract: a case report].
AB  - We report a 33-year-old man who manifested spastic paraplegia with congenital
      cataract, dementia, deformity of the foot (pes cavus, high arch and hammer toes),
      ataxia, and peripheral neuropathy. Magnetic resonance imaging showed mild
      deformity of the trunk of the corpus callosum and atrophy of superior cerebellar
      vermis. Metabolic diseases were ruled out by the clinical course and special
      examinations. Other patients, including 2 of ours, with spastic paraplegia and
      thin corpus callosum have been reported, but the present case is different
      because of congenital cataract and the form of the corpus callosum. We consider
      that there may be a variety of complicated forms of spastic paraplegia. To assess
      the etiology of complicated forms of spastic paraplegia, further case
      accumulation is very important.

PMID- 9597909
TI  - [A case of acute multifocal motor neuropathy with conduction block after
      Campylobacter jejuni enteritis].
AB  - The patient was a 25-year-old male with acute multifocal motor neuropathy with
      conduction block (MMNCB) after Campylobacter jejuni enteritis. After having
      suffered from diarrhea for 3 days, he rapidly developed asymmetrical distal
      dominant muscle weakness in all extremities. Sensory disturbance was unremarkable
      except for slight disturbance in deep sensation. Deep tendon reflexes were normal
      throughout the course of present illness. CSF analysis revealed increased protein
      up to 66 mg/dl without pleocytosis. In electrophysiological examinations,
      persistant multifocal conduction blocks in the motor nerves were predominantly
      noted in the distal part of the extremities. Serum titers of anti-Campylobacter
      jejuni antibody, anti-GM1 antibody and anti-GalNAc-GD1a antibody were elevated.
      Muscle weakness resolved completely within 7 weeks. The sural nerve biopsy did
      not reveal either axonal degeneration, nor demyelination. These clinical and
      laboratory findings suggested that this case was most likely an acute type of
      MMNCB after Campylobacter jejuni enteritis.

PMID- 9597910
TI  - [Progressive multifocal leukoencephalopathy (PML). Report of a case diagnosed by
      amplification of JC virus DNA from cerebrospinal fluid (CSF)].
AB  - We report a 54-year-old Japanese man who was diagnosed as progressive multifocal
      leukoencephalopathy (PML). He had been maintained on regular hemodialysis for 10
      years. He was admitted to our hospital with chief complaints of visual
      disturbance and disorientation. On neurological examination, he was somnolent,
      and showed mild weakness in the right upper and lower limbs. Deep tendon reflexes
      were brisk on the right upper and bilateral lower limbs. Sensory examination
      revealed no abnormal findings. The cerebrospinal fluid (CSF) showed five
      mononuclear cells/mm3, protein 39 mg/dl and glucose 38 mg/dl. Brain MRI revealed
      multiple hyperintense lesions in T2-images, which were confined to the white
      matter of bilateral occipital and the left frontal lobes without an enhancement
      after gadolinium administration. Using polymerase chain reaction, we amplified
      the JCV regulatory region from the CSF of the patient. The amplified product
      contained a rearranged regulatory region that could have been generated from the
      archetype by deletion and amplification. PML was diagnosed on the basis of these
      findings. The patient died 7 months after onset of the symptoms. The diagnosis of
      PML was confirmed by the postmortem findings. The present case indicates that PCR
      of JCV from CSF is very useful for definitive diagnosis of PML.

PMID- 9597911
TI  - [A case of chronic, motor, axonal polyneuropathy successfully treated by
      immunoadsorption].
AB  - We reported a 61-year-old male with chronic, motor, axonal polyneuropathy.
      Neurological examination revealed severe muscle weakness in the proximal parts of
      the four limbs. Sensory examination was normal. The cerebrospinal fluid protein
      was elevated to 74 mg/dl, and the cell count was normal. The serum antibodies to
      GM1, GD1a, GD1b, and GQ1b were all negative. Electrophysiological studies showed
      reduced compound muscle action potentials (CMAPs) suggesting axonal neuropathy,
      and the nerve conduction velocity was only mildly reduced. After treatment with
      plasmapheresis (PP) by the immunoadsorption method, his symptoms significantly
      improved in three weeks, and the cerebrospinal fluid protein, and CMAPs also
      improved. Only a few studies have been reported regarding patients with chronic,
      motor dominant, axonal polyneuropathy that responded to immunosuppressive
      therapies or PP. It remains to be determined whether chronic, dominantly motor,
      axonal polyneuropathy as seen in the present case is a subtype of chronic
      inflammatory demyelinating polyradiculoneuropathy (CIDP) or a primary axonal
      immune-mediated neuropathy that is different from CIDP. At present we are not
      able to answ what kind of clinical or laboratory markers other than an elevated
      cerebrospinal fluid protein level may help to predict a positive response to
      immunosuppressive therapy or PP.

PMID- 9597912
TI  - [A management for severe acquired stuttering in a case of pure akinesia
      syndrome].
AB  - We reported a 73-year-old man with pure akinesia syndrome who showed severe
      acquired stuttering and paradoxical kinesia on speech. He was evaluated in
      another hospital for bradykinesia and frozen gait at age of 67 when his cranial
      MRI disclosed ischemic changes in bilateral basal ganglia and periventricular
      deep white matter. The treatment with L-dopa and L-threo DOPS was not effective.
      His symptoms were slowly progressive and got worse gradually. At age of 72, he
      began to have difficulty in speech due to severe acquired stuttering, and one
      year later, he visited our hospital. The diagnosis of pure akinesia syndrome was
      made because of akinesia, micrographia, marked frozen gait with paradoxical
      kinesia and disturbance of postural reflex without tremor and rigidity. His
      speech showed severe acquired stuttering with marked blocking and repetition of
      initial phonemes at the beginning of speech. But intelligible speech recurred
      with pointing the characters by his finger or with writing an initial letter of
      word, although his speech was small and monotonous. Surface EMG findings of
      muscles participating speech in acquired stuttering showed the similar tonic
      discharge to those of muscles of lower extremity in frozen gait. These results
      implied that freezing phenomenon and festination of muscles participating speech
      in our patient may result in acquired stuttering.

PMID- 9597913
TI  - [Serum concentration of coenzyme Q in xeroderma pigmentosum].
AB  - Serum concentrations of CoQ were measured on 22 xeroderma pigmentosum (XP)
      patients. 10 severely handicapped patients and 32 healthy children and adults.
      CoQ levels in XP patients (0.5 +/- 0.16 microgram/ml) and handicapped patients
      (0.57 +/- 0.21 microgram/ml) were lower than those in healthy children and adults
      (0.73 +/- 0.2 microgram/ml). CoQ levels in XP patients tended to decrease with
      age and were extremely low in two bed-ridden patients (0.29 and 0.21
      microgram/ml), suggesting that CoQ levels decreased with disease progression. We
      studied the clinical effects of CoQ therapy in 19 XP patients with low CoQ
      levels. Eight patients showed increased activity in daily life. It suggests that
      XP patients have the disturbance of energy metabolism due to mitochondrial
      dysfunction. We consider it is worthwhile to research the mitocondrial function
      and the trial of CoQ therapy on XP patients.

PMID- 9597914
TI  - [Coxsackie virus B4 encephalitis in a young female who developed mental symptoms,
      and consciousness disturbance, and completely recovered].
AB  - An 18-year-old female had common cold and insomnia in early March 1987. Later,
      abnormal speech and behavior, emotional incontinence, anorexia and consciousness
      disturbance appeared. On March 19, she was admitted to our hospital in semi
      comatose state. Myoclonus-like movement on hands was observed, and epileptic
      attacks with tonic and clonic convulsions occasionally occurred. There were no
      neurological findings that suspected cerebral focal lesions. The respiration was
      assisted through tracheal intubation. Laboratory examinations showed inflammatory
      reactions (CRP+2, WBC 10,600) and transient high levels serum CK (6,215 IU). As
      she had bradycardia (30-40/min) with complete AV block on ECG, the pacemaker was
      implanted. The complication of myocarditis was suspected. EEG showed bilateral
      slow waves (3-6Hz), dominantly in frontal areas. Brain CT and CSF examinations
      were normal. After the combined administration of ara-A, dexamethasone and anti
      convulsant, the consciousness level was recovered within a month. The serum
      antibody against coxsackie virus B4 alone was significantly increased. We
      concluded that coxsackie virus B4 caused acute encephalitis with mental symptoms
      and myocarditis with AV block. Recently, cytomegalovirus was reported to be the
      causative virus in a young female with non-HSV encephalitis who showed mental
      symptoms with good prognosis, but coxsackie virus B4 should also be considered as
      one of the causative viruses.

PMID- 9597915
TI  - [Acute isolated levator palpebral myositis].
AB  - A 17-year old man developed acute onset blepharoptosis of the right upper eyelid
      with swelling. On examination, the patient exhibited right blepharoptosis without
      limitation of eye movement. MRI revealed swelling of right levator palpebral
      muscle. Oral steroid administration led to complete resolution of the
      blepharoptosis within 3 weeks. Isolated levator palpebral myositis is a rare
      disease, but, it is important for differential diagnosis on patients with
      blepharoptosis.

PMID- 9597916
TI  - [Asymptomatic cerebral infarction associated with a patent foramen ovale and
      atrial septal aneurysm].
AB  - We reported two young adults (a 42-year-old female and a 45-year-old male) with
      tension type headache who had a patent foramen ovale and atrial septal aneurysm
      demonstrated by transesophageal echocardiography, associated with asymptomatic
      cerebral infarctions. There were multiple subcortical infarctions in the frontal
      and parietal lobes in case 1, and cerebral infarctions in the right corona
      radiata, head and body of the caudate nucleus, and putamen in case 2. The two
      cases did not have hypertension, diabetes mellitus, hyperlipidemia, cardiac
      diseases detected by electrocardiography and transthoracic echocardiography, and
      abnormality of intracranial and extracranial arteries by ultrasound sonography
      and cerebral angiography. Transeosophageal echocardiography revealed atrial
      septal aneurysm, and showed right-to-left shunt (patent foramen ovale) by
      Valsalva maneuver. Two cases were diagnosed as paradoxical cerebral embolism
      associated with a patent foramen ovale. If asymptomatic cerebral infarctions are
      cryptogenic stroke, a patent foramen ovale and atrial septal aneurysm should be
      examined by transesophageal echocardiography with Valsalva maneuver.

PMID- 9597917
TI  - [Creutzfeldt-Jakob disease associated with ocular dipping--a case report].
AB  - We presented a case of Creutzfeldt-Jakob disease (CJD) associated with ocular
      dipping (OD). A 65-year-old woman was hospitalized with two months history of
      progressive ataxia and mental deterioration. On admission, she was bed-ridden and
      stuporous with rigidity of the four limbs. Her both eyes were noted to deviate
      downward slowly from midpossition, taking 1 to 3 seconds to reach the nadir and
      rapidly returned to midpossition. It was felt that these abnormal eye movements
      are compatible with OD. Findings of EOG were compatible with that of typical OD.
      Electroencephalogram obtained a few months later revealed periodic synchronous
      discharge. Magnetic resonance imaging of the brain which had demonstrated mild
      cerebral atrophy in the beginning subsequently revealed full-brown cerebral
      atrophy. Hence, she was diagnosed of having CJD. There has been no report of CJD
      associated with OD. The OD was observed to last as long as 110 days. When the
      above described abnormal eye movements were noted, there was no signs indicative
      of brain stem dysfunction present. Therefore, we feel that the present case
      suggest that a diffuse cerebral dysfunction involving the cerebral cortex and
      basal ganglia may underlie in the development of OD.

PMID- 9597918
TI  - Expanded programme on immunization (EPI). Measles elimination in Oman.

PMID- 9597919
TI  - Meningitis in Chad.

PMID- 9597920
TI  - 2-Methoxyisobutylisonitrile probe during parathyroid surgery: tool or gadget?
AB  - The success of parathyroid surgery is determined by the identification and
      removal of all parathyroid tumors. Parathyroid tumors accumulate and retain 2
      methoxyisobutylisonitrile (MIBI) labeled with technetium-99m. Intravenous
      injection of this radiopharmacon prior to parathyroid surgery allows
      identification of parathyroid tumors with a hand-held gamma detector. To assess
      the value of this technique, a case-control study was performed with 62 patient
      having nuclear-guided parathyroidectomy and 60 patients having conventional
      parathyroid explorations. The sensitivity rates of the MIBI probe in single and
      multiple gland disease were 84.6% and 63.0%, respectively. Rates of success,
      temporary and permanent hypoparathyroidism, and injury of the recurrent laryngeal
      nerve were similar in patients who underwent probe-guided surgery and those who
      had conventional surgery. In conclusion, although the MIBI probe appears to be a
      valuable tool in parathyroid surgery, its use has not improved the outcome of
      such surgery at our institution.

PMID- 9597921
TI  - Prospective surgical outcome study of relief of symptoms following surgery in
      patients with primary hyperparathyroidism.
AB  - Many of the symptoms experienced by patients with primary hyperparathyroidism
      (HPT) develop insidiously and have often been misinterpreted as normal aging. The
      purpose of this study was to quantify HPT patients' preoperative symptoms
      prospectively and study the impact of successful surgical intervention on these
      symptoms. Altogether 63 consecutive patients with primary HPT and 54 comparison
      patients with nontoxic thyroid disease were prospectively enrolled in the study.
      An outcome questionnaire documenting symptoms with a visual analog scale (VAS)
      was used. The questionnaire was filled out preoperatively and at 7 to 10 days and
      3 and 12 months postoperatively. At 1 year the questionnaire also included a
      general health assessment and quality of life index. Demographic data and follow
      up blood work was obtained. Descriptive statistics, parametric comparisons (t
      tests, ANOVA), and nonparametric comparisons (Mann-Whitney U-test) were
      calculated. The HPT group demonstrated a significant decrease in reported
      symptoms between the preoperatively assessment and 7 to 10 days after operation
      (p < 0.001). There were no further statistically significant decreases in the HPT
      group's symptoms at 3 and 12 months, but there was a trend for these symptoms to
      decrease over time. HPT patients perceived a 60% increase in their general health
      at 1 year; the comparison group perceived no increase. There was no significant
      change in the symptoms reported by the comparison group between each of the study
      intervals. Surgical intervention on HPT patients significantly reduces
      preoperative symptoms, and this reduction is most marked within the first 10 days
      after surgery.

PMID- 9597922
TI  - Fibroblast growth factors and their receptors in parathyroid disease.
AB  - Fibroblast growth factors (FGFs) comprise a family of polypeptide growth factors
      implicated in the control of proliferation of glandular tissues. The aim of this
      study was to determine whether FGFs are produced in normal and abnormal
      parathyroid glands and if these tissues have the potential to respond to this
      growth factor family. We have examined the expression of FGF receptor (FGF-R)
      types 1 and 2 and of FGFs 1, 2, 3, and 7 in a series of human parathyroid tissues
      using the reverse transcription polymerase chain reaction (RT-PCR). Samples of 10
      parathyroid adenomas and 10 hyperplastic glands from patients with renal
      hyperparathyroidism (HPT) were compared with samples from normal parathyroid
      glands from patients with primary HPT in the study. FGF-R1 was expressed in all
      samples and FGF-R2 in most. FGF1 and FGF2 were expressed in all samples at
      variable levels, with no correlation between disease type and amplified RT-PCR
      product levels. FGF7 was expressed in normal parathyroid tissue and in all
      adenomas but was absent in all but one of the hyperplastic parathyroid glands
      from renal failure patients. FGF3 was expressed at low levels in normal tissue
      and variably expressed in diseased tissue, in some instances at high levels.
      These findings suggest that parathyroid tissue is potentially responsive to FGFs.
      The absence of FGF7 expression in all but one of the renal parathyroid samples
      compared with normal and adenomatous tissue requires further investigation. The
      presence of elevated levels of FGF3 expression in abnormal parathyroid tissue may
      be significant, as the FGF3 gene (int-2 proto-oncogene) is located on chromosome
      11q13.3, a region already identified as being susceptible to
      rearrangement/mutation in parathyroid disease.

PMID- 9597923
TI  - Late outcome of 304 consecutive patients with multiple gland enlargement in
      primary hyperparathyroidism treated by conservative surgery.
AB  - The aim of this study was to assess the late outcome of patients with primary
      hyperparathyroidism and multiple gland enlargement (MGE) treated by conservative
      surgery. MGE in primary hyperparathyroidism is the presence of two or more
      enlarged glands weighing more than 50 mg. Conservative surgery consists in
      resecting the grossly enlarged glands without biopsying the normal glands. Some
      authors have suggested that this approach overlooks minute hyperplasia, leading
      to late recurrences of hyperparathyroidism; conversely, it may result in the
      unnecessary resection of grossly enlarged, but not hyperfunctioning, glands.
      Altogether 1231 patients were operated on for primary hyperparathyroidism between
      1966 and 1995. Of these patients, 304 (24.9%) had MGE, including 42 cases of
      multiple endocrine neoplasia (MEN), 12 familial cases, and 250 seemingly sporadic
      cases. Two, three, or four glands (or more) were involved in 61.8%, 21.4%, and
      16.4% of cases, respectively. During the early postoperative period one patient
      died and ten were reoperated for persistent hypercalcemia. The pathologic
      diagnoses were double adenomas (13.5%), hyperplasia (35.8%), association of the
      two (39.8%), and a normal second gland (10.8%) on light microscopy findings. None
      of the 30 deaths that occurred during follow-up was related to
      hyperparathyroidism. Altogether 190 patients (79%) were available for follow-up
      (average 89.3 months): 90% were normocalcemic, 4.7% hypocalcemic, and 5.2%
      hypercalcemic. A late iPTH assay was done in 147. PTH was appropriate to the
      serum calcium level in 84.3% and appropriate to normal calcemia in 91.6% of 132
      cases. Conservative surgery is thus an acceptable treatment for MGE in patients
      with hyperparathyroidism. Few late recurrences occur, for which there are no
      individual predictive criteria.

PMID- 9597924
TI  - Parathyroidectomy in the elderly: do the benefits outweigh the risks?
AB  - Although the incidence of hyperparathyroidism (HPT) in the elderly exceeds 1.5%,
      limited resources and co-morbidity inhibit referral for parathyroidectomy. To
      determine the risks and benefits of surgery, we examined the outcomes of elderly
      patients who underwent exploration for primary HPT. Data from 211 consecutive
      patients who underwent parathyroidectomy by one surgeon at the Johns Hopkins
      Hospital between August 1990 and May 1996 were recorded prospectively. Of these
      patients, 184 had primary HPT. Demographic and outcome data of elderly patients
      (> 70 years of age) (n = 36) were compared to those from younger patients (< 70
      years of age) (n = 148). Preoperative symptoms of mental impairment, bone
      disease, and fatigue were more common in elderly patients (p < 0.05), and
      nephrolithiasis was more frequent in younger patients (p < 0.025). Elderly
      patients presented with more advanced disease, manifested by higher preoperative
      parathyroid hormone levels (301.9 +/- 63.3 vs. 169.2 +/- 14.3 pg/ml, p < 0.05).
      The cure rate (94.4%), morbidity (5.5%), and mortality (0%) in the elderly were
      indistinguishable from those of their younger cohorts (98%, 1.4%, and 0%,
      respectively). In conclusion, the more advanced disease seen in the elderly
      suggests that they are referred for surgery with a higher threshold than younger
      patients. Although several series of parathyroidectomy in elderly patients have
      reported high morbidity rates, significant mortality, and long length of stay
      (LOS), we found that parathyroidectomy in these patients can be performed with
      high cures, low morbidity, no mortality, short LOS, and high patient
      satisfaction. These data suggest that the benefits of surgery outweigh its risks
      and argue for a lower threshold for referral of elderly patients with primary HPT
      for surgical treatment.

PMID- 9597925
TI  - Surgical management of amiodarone-associated thyrotoxicosis: too risky or too
      effective?
AB  - Amiodarone-associated thyrotoxicosis, often clinically mild and resolutive after
      amiodarone discontinuation or under medical therapy, is sometimes drug
      unresponsive and not uncommonly follows a dramatic, even fatal course. Therefore,
      we considered a surgical solution in 15 severely amiodarone-associated thyrotoxic
      patients. Twelve men and three women (mean age 68 years, range 50-84 years)
      underwent radical thyroidectomy for clinical and biologically proved amiodarone
      associated thyrotoxicosis. In six surgery was the first-line therapeutic option.
      In the other nine thyroidectomy seemed unavoidable considering the
      unresponsiveness to medical therapy and rapid deterioration of the patients'
      clinical condition, with life-threatening cardiac failure in three. In every
      patient surgery was conducted without immediate or delayed complications. Total
      thyroidectomy proved uniformly, definitively, and rapidly effective in
      controlling thyrotoxicosis in all patients, with a spectacular reversal of
      cardiac failure in the three most critical cases. Surgery was beneficial to our
      15 patients and undoubtedly life-saving in the three most worrying cases. These
      results suggest that thyroidectomy should be more liberally regarded as an
      interesting alternative to conventional, but unpredictably effective, medical
      therapies.

PMID- 9597927
TI  - Desensitization in normal and neoplastic human thyroid cell lines.
AB  - Because some papillary thyroid cancers continue to grow when thyroid-stimulating
      hormone (TSH) levels are suppressed, we questioned whether desensitization (i.e.,
      a decreased cAMP response to repeat stimulation with TSH) occurs in normal and
      neoplastic thyroid tissue. If desensitization does occur, is it similar or
      different in these human thyroid cells? Normal and papillary thyroid cancer cells
      from the same patient were cultured as we have previously described. Normal and
      neoplastic thyroid tissues responded to TSH (0.01-10.0 mU/ml) by increasing cAMP
      production and growth in a dose-dependent manner. In normal cells there was an 11
      fold mean increase in cAMP production at 4 hours, and all thyroid cultures
      responded. In neoplastic cells cAMP production increased from 1.5-fold to 3.0
      fold with a mean 2.0-fold increase at 4 hours. In normal thyroid cells the cAMP
      response to a second TSH stimulus (desensitization) decreased up to 75% (range 25
      75%), and desensitization occurred in all normal thyroid cell cultures. In
      neoplastic thyroid cells, however, the cAMP response to a second TSH stimulus
      decreased up to 17% (range 0-17%); and desensitization occurred in only two of
      the five neoplastic thyroid cell cultures. Thus when normal thyroid and
      neoplastic cells from the same patients were studied, greater desensitization
      occurred in the normal cells (75% vs. 17%). These studies document that there is
      greater desensitization in normal tissue than in neoplastic thyroid tissue, which
      may account for the increased growth of thyroid neoplasms in the presence of ever
      changing low levels of TSH.

PMID- 9597926
TI  - Heterologous desensitization in neoplastic thyroid cells: influence of the
      phospholipase C signal transduction system on the thyrotropin-adenylate cyclase
      signal transduction system.
AB  - Desensitization is defined as a decreased functional response after continuous or
      repetitive stimulation of a receptor with its agonist. Thyrotropin (TSH)
      increases cAMP levels in normal and neoplastic thyroid tissue. The tumor promoter
      12-O-tetradecanoyl-phorbol-13-acetate (TPA) activates protein kinase C (PKC). The
      aim was to determine whether TPA induces heterologous desensitization of the TSH
      adenylate cyclase (AC) signal transduction system. Three human thyroid neoplasms
      in culture for 6 months or longer (one papillary carcinoma, one Hurthle cell
      carcinoma, one follicular adenoma) were incubated with TSH (10 mU/ml) and TPA
      (1.6 x 10(-8) M) separately and together for various time periods (from 10
      minutes to 24 hours). The mixture was subsequently incubated for 30 minutes with
      TSH. TPA alone had no effect on cAMP levels, but co-incubation of TPA and TSH
      caused a significant reduction in cAMP response when compared to the cAMP
      response that resulted after stimulation with only TSH (p < 0.001). cAMP levels
      in response to TSH decreased by 31%, 44%, and 57% after preincubation with TSH
      for 10 minutes, 4 hours, and 24 hours, respectively (p < 0.01; ANOVA). Co
      incubation of cells with TPA and staurosporine (10 ng/ml), a PKC inhibitor,
      prevented the effect of TPA on desensitization at 10 minutes and blunted the
      effect at 4 hours. This is the first demonstration in human neoplastic thyroid
      cells that TPA induced heterologous desensitization of the cAMP response to TSH.
      This TPA-induced effect appears to involve PKC activation, as it can be blocked
      by staurosporine.

PMID- 9597928
TI  - Gene rearrangement of immunoglobulin as a marker of thyroid lymphoma.
AB  - Thyroid lymphoma occurs most commonly in the thyroid gland in association with
      Hashimoto's thyroiditis. Histologic findings occasionally cannot distinguish
      lymphoma from Hashimoto's thyroiditis, which creates a serious problem of whether
      treatment should be initiated. For this study, we examined 33 lymphoma tissues
      and 10 thyroid tissues from patients with Hashimoto's thyroiditis for the
      presence of gene rearrangement of immunoglobulin, which represents clonality of B
      cell-derived tumors. Genomic DNA from thyroid tissues was digested with Bam H1
      and Hind III restriction enzymes followed by electrophoresis. A Southern blot was
      performed with an IgH-JH probe or IgL-J kappa probe to detect gene rearrangement.
      Of the 33 lymphoma tissues, 27 (85%) showed gene rearrangement of immunoglobulin,
      whereas none of Hashimoto's thyroiditis tissue showed gene rearrangement. Five
      patients with a positive histologic diagnosis of lymphoma showed a negative gene
      rearrangement and were treated as having lymphoma. We encountered one case of
      lymphoma (plasmacytoma) in which gene rearrangement (not histologic findings) was
      diagnostic. Gene rearrangement of immunoglobulin can be used to detect thyroid
      lymphoma, particularly when the histologic diagnosis is inconclusive. The
      sensitivity of detecting thyroid lymphoma by the Southern blot method was about
      85% in the present series.

PMID- 9597929
TI  - Determinative factors of biochemical cure after primary and reoperative surgery
      for sporadic medullary thyroid carcinoma.
AB  - Normalization of calcitonin levels after surgery has been regarded as the most
      powerful prognostic factor for medullary thyroid carcinoma (MTC). Although the
      prognosis of patients with persistent hypercalcitoninemia may be acceptable, the
      biochemical cure rate can be improved by new microdissection techniques. This
      raises certain questions: Can extension of locoregional lymphadenectomy (LA)
      further improve biochemical cure and survival after primary or reoperative MTC
      surgery? Which factors concerning TNM categories are associated with the
      possibility of postoperative normalization of calcitonin levels? This study
      included 64 patients with sporadic MTC operated on from 1986 to 1997. Altogether
      27 patients underwent primary surgery, and 37 patients were reoperated,
      performing a microdissection of all four locoregional compartments (four
      compartment lymphadenectomy, or 4CLA). For primary MTC the biochemical cure rate
      was 100% in node-negative patients and 33% in node-positive patients; the latter
      could be improved to 45% after 4CLA. In contrast to reoperative MTC, the rate of
      lymph node metastases (LNMs) with primary MTC correlated with the pT category
      (pT1 33%, pT2 53%, pT3 100%, pT4 100%) but not with age or sex. Again in contrast
      to reoperative MTC, mediastinal LNMs in primary MTC were present only in patients
      with a pT4 tumor. At reoperation, 4CLA was able to cure 22% of node-positive
      patients, 28% without proved distant metastases. No patient with extrathyroidal
      tumor involvement or distant metastases was biochemically cured after either
      primary or reoperative surgery. For all node-positive MTC patients, in addition
      to cervicocentral LA at least a bilateral cervicolateral LA is recommended.
      Transsternal mediastinal lymph node dissection is indicated in patients with LNMs
      in the cervicomediastinal transition, facilitating biochemical cure in up to 45%
      after the first operation and 22% after reoperative surgery of sporadic MTC.

PMID- 9597930
TI  - Redifferentiation therapy with retinoids: therapeutic option for advanced
      follicular and papillary thyroid carcinoma.
AB  - During the course of tumor progression the differentiated morphologic and
      functional characteristics of differentiated thyroid carcinomas (DTC) disappear.
      This corresponds to more aggressive growth, metastatic spread, and loss of iodine
      uptake. Experimental data give strong evidence that differentiated functions of
      iodine metabolism can be reinduced by retinoic acids. Results of a study
      performed in patients with advanced DTC are presented. Twenty patients with DTC
      (eight follicular, seven papillary, five oxyphilic) were selected for treatment
      with retinoic acid 1.5 mg/kg body weight/day over 5 weeks. All patients had
      advanced tumor stages with prior operative and radioiodine treatment. Extensive
      tumor invasion, distant metastatic spread, or insufficient or no radioiodine
      uptake precluded any conventional therapeutic option. The aim was to assess the
      changes under retinoid treatment. Iodine uptake increased in eight patients
      (three follicular, three papillary, two oxyphilic). Thyroglobulin (TG) as
      parameter for tumor mass and differentiation increased in 12 (63%) patients,
      decreased in 6 (32%), and did not change in 1 (5%). Retinoids do have an effect
      on differentiation status of DTC, reinducing iodine uptake in 50% of patients. TG
      levels do not always parallel a response in iodine uptake.

PMID- 9597931
TI  - Role of fine-needle aspiration biopsy and frozen section examination in
      determining the extent of thyroidectomy.
AB  - Traditionally the extent of thyroidectomy in patients with nodular thyroid
      disease has been based on peroperative frozen section examination (FS). Fine
      needle aspiration biopsy (FNAB) and FS were evaluated with regard to the
      reliability to determine whether an operation for cancer is necessary. Both
      methods were performed in 240 patients operated for nodular thyroid disease and
      compared with the final histology on paraffin sections. Altogether 72 (30%)
      patients were found to have a malignant lesion on final histology. Only a
      malignant FNAB diagnosis and a malignant FS diagnosis were considered positive
      results for determining the extent of thyroidectomy. The test characteristics
      were equal: the sensitivity of FNAB and FS was 67%, the specificity 99%, and the
      accuracy 89%. The positive predictive value was 96% for FNAB and 98% for FS; the
      negative predictive values were 88% and 87%, respectively. Further analysis of
      the results indicates that FS is not necessary for patients with a malignant FNAB
      result. These patients should undergo a therapeutic operation for malignancy.
      When the FNAB result is uncertain, patients should undergo diagnostic surgery,
      and definitive surgery should be based on the final histology. Routine use of FS
      can be omitted.

PMID- 9597932
TI  - Lethality of multiple endocrine neoplasia type I.
AB  - The lethality of the endocrine tumors associated with multiple endocrine
      neoplasia type I (MEN-I), particularly the pancreatic islet cell tumors, has been
      controversial. We evaluated the cause and age of death in MEN-I kindreds. Our
      database contains 34 distinct kindreds with 1838 members. Reliable death data are
      available for 103 people (excluding accidents and age < 18 years). We compared
      survival curves of MEN-I patients who died from causes related to MEN-I with
      those from MEN-I carriers who died from a nonendocrine cause and unaffected
      kindred members. We also compared ages of death between affected and unaffected
      members of MEN-I kindreds. Of 59 MEN-I-affected patients, 27 died directly of MEN
      I-specific illness and 32 of non-MEN-I causes. The MEN-I-specific deaths occurred
      at a younger age (median 47 years) than either MEN-I patients whose death was
      from some nonendocrine cause (median 60 years, p < 0.02) or than all kindred
      members who did not die of MEN-I disease (median 55 years, p < 0.05). The causes
      of death of the MEN-I patients included islet cell tumor (n = 12), ulcer disease
      (n = 6), hypercalcemia/uremia (n = 3), carcinoid tumor (n = 6), and nonendocrine
      malignancies (n = 9). There was no difference in survival between MEN-I carriers
      and unaffected kindred members. Of our MEN-I patients, 46% died from causes
      related to their endocrine tumors after a median age of 47 years, which was
      younger than family members who did not die from these tumors. Pancreatic islet
      cell tumors were the most common cause of death of MEN-I patients. Management of
      kindreds with MEN-I should include an aggressive screening program with early
      therapeutic intervention when a tumor is identified.

PMID- 9597933
TI  - Neuroendocrine tumor imaging: can 18F-fluorodeoxyglucose positron emission
      tomography detect tumors with poor prognosis and aggressive behavior?
AB  - We evaluated the clinical value of positron emission tomography (PET) using 18F
      fluorodeoxyglucose (FDG) for neuroendocrine tumor (NET) detection. Sixteen
      patients with cytologically or histologically proved NETs were investigated.
      Patients were divided in two groups of eight patients each according to the
      clinicopathologic features related to prognosis: slow-growing NETs and aggressive
      NETs. Results of FDG tumor uptake as detected by PET were compared with computed
      tomography (CT) scans and with scans obtained with 111In-octreotide scintigraphy
      (n = 13). Tumor FDG uptake was increased in the primary lesion of all eight
      aggressive NETs; the tracer was shown also in lymph nodes, liver metastases, or
      both in five of six of them (83%). In four cases, additional unknown tumor sites
      undetected by CT scan were identified. A slight positivity was found in only one
      of eight cases with a slow-growing NET. The overall octreotide scintiscan
      sensitivity was 85%, but in the aggressive NETs it failed to detect the primary
      lesion in two of seven cases. Uptake of the tracer in some but not all tumor
      lesions in the same patient was seen by both FDG-PET and octreotide scintiscans.
      From our limited experience 18F-FDG PET seems to be useful for identifying NETs
      characterized by rapid growth or aggressive behavior. Uptake of the FDG tracer by
      the tumor may be related to a worse prognosis. Despite the heterogeneity of
      tracer uptake in the various lesions of NETs with multiple tumor sites, FDG-PET
      was able to detect unsuspected distant metastases, contributing to better staging
      of advanced disease.

PMID- 9597934
TI  - Preoperative and intraoperative topographic diagnosis of insulinomas.
AB  - Altogether 120 patients with organic hyperinsulinism underwent clinical
      examination and treatment (38 male, 82 female, mean age 44.2 +/- 4.6 years). The
      cause of hyperinsulinism was benign insulinomas in 96 (80.0%), malignant tumors
      in 9 (7.5%), and hyperplasia of beta cells in 6 (5.0%). In 9 (7.5%) patients the
      origin of hyperinsulinism was not diagnosed. The tumor was localized in the head,
      body, and tail of the pancreas in 31.8%, 36.4%, and 31.8% of cases, respectively.
      Intraoperative ultrasonography (IOUS) was undertaken in 37 patients, and in 83
      cases only intraoperative palpation was done. Arterial stimulated venous sampling
      (ASVS) was performed in 17 patients (blood was sampled from the right hepatic
      vein for determination of the insulin level after arterial stimulation by calcium
      gluconate in different parts of the pancreas). The sensitivity of ultrasonography
      (US) was 29.5%, computed tomography (CT) 24.2%, angiography 55.9%, superselective
      angiography (branches of the celiac trunk) 72.2%, and intraoperative palpation
      90.0%. ASVS showed an accuracy of 90.0%. Combining angiography with ASVS gave an
      exact diagnosis of hyperinsulinism in 100% of cases, and IOUS revealed tumors in
      100% of cases. Hyperplasia of beta-cells was diagnosed only by means of ASVS. A
      total of 117 patients underwent surgery, including distal resection of pancreas
      (n = 39), enucleation of tumor (n = 70), and laparotomy (n = 8). The
      postoperative mortality associated with insulinomas was 7.7%. The frequency of
      postoperative complications was 43.6%. Benign insulinomas recurred at a rate of
      5.4%. Patients with malignant insulinomas had a 5-year survival of 66.0%. The
      diagnosis of insulinomas was achieved by a combination of selective angiography,
      ASVS, and IOUS.

PMID- 9597935
TI  - Can adrenal incidentalomas be safely observed?
AB  - We currently recommend excision of adrenal incidentalomas > or = 4 cm in size and
      all hormonally active tumors. The optimal management and follow-up of smaller
      nonfunctioning tumors are controversial. The aim of this study was to determine
      the clinical outcome of a well defined population of patients with incidentalomas
      followed without operative intervention. The study group comprised 231 patients,
      identified from the records of abdominal or thoracic computed tomographic (CT)
      scans performed between 1985 and 1989. The primary outcome variable analyzed was
      survival. Follow-up was obtained by office records, telephone contact, or letter.
      There were 101 male and 130 female patients with a mean age at diagnosis of 64
      years (range 5-86 years). Most adrenal tumors were unilateral (right 113; left
      98); 20 were bilateral. Mean tumor size was 2 cm (range 1-6 cm). In nine (4%)
      patients the tumor was > or = 4 cm. Follow-up [mean 7 years; range 1 month
      (patient died) to 11.7 years] was complete in 224 (97%) patients. Ninety-one
      (39%) patients had one or more additional CT scans performed during the follow-up
      period, with only four patients demonstrating a > 1 cm increase in the size of
      the adrenal mass. Surgical excision of these four lesions identified benign
      pathology. Eighty-one (35%) patients died of conditions unrelated to adrenal
      pathology. No patient developed subsequent adrenal hyperfunction or adrenal
      malignancy. Within the context of our guidelines, conservative management of
      adrenal incidentalomas considered benign or nonfunctioning at diagnosis is
      appropriate. Additional information provided by repeat CT scanning appears to
      confer limited benefit. This study does not support laparoscopic removal of
      small, nonfunctional adrenal tumors, as has been suggested.

PMID- 9597936
TI  - Adrenocortical carcinoma: surgery and mitotane for treatment and steroid profiles
      for follow-up.
AB  - Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. It has
      been difficult to establish a strict treatment program for ACC, and better
      treatment alternatives and diagnostic tools must be sought. Even though surgery
      is the treatment of choice, the role of surgery in advanced disease has been
      questioned. Eighteen consecutive patients were treated at our unit over a 22-year
      period (1975-1997). All patients underwent surgery and were followed by our
      protocol, which includes urinary steroid profiles, clinical examinations,
      analysis of steroid hormones, and radiologic investigations. Twelve patients
      received mitotane with drug concentration measurements to deliver an effective,
      nontoxic dose. The median duration of mitotane treatment was 12 months. Few side
      effects were observed. Four patients with low-stage tumors underwent second-look
      operations with no pathologic findings. Five patients were subjected to repeat
      operations, and the mean duration of the disease-free interval before repeat
      surgery for these patients was 59 months. There was a significant positive
      correlation between the disease-free interval and the observed survival after
      repeat surgery. Eleven patients with intentionally curative surgery had their
      urinary steroid profiles tested several times postoperatively. For five patients
      preoperative urine samples were also available. Steroid profiles indicated
      recurrent disease despite normal radiologic findings in two of these five
      patients. The follow-up ranged from 6 weeks to 24 years. The predicted 5-year
      survival was 58% according to the Kaplan-Meier method. We conclude that
      monitoring serum concentrations of mitotane makes long-term treatment possible
      with few side effects; steroid profile analysis can be used for early detection
      of tumor recurrence; and repeat surgery for recurrence is of value for patients
      with long disease-free intervals.

PMID- 9597937
TI  - Laparoscopic versus open posterior adrenalectomy: comparison of acute-phase
      response and wound healing in the cushingoid porcine model.
AB  - This prospective randomized study examined the acute-phase response and wound
      healing, comparing laparoscopic (LA) and open posterior (PA) adrenalectomy in a
      cushingoid porcine model. Repository corticotropin gel was given to 40 pigs for
      21 days. Biochemical and tissue parameters of Cushing syndrome were confirmed.
      The pigs were randomized to undergo LA or PA. In addition to operating time and
      morbidity, the acute-phase response was compared by measuring the postoperative
      white blood cell count, fasting glucose, C-reactive protein, and nitrogen
      balance. Wound healing was assessed by (1) scored (1-4) gross appearance at 48
      hours and 1 and 2 weeks; (2) histologic examination; and (3) tensile strength.
      There was no difference in operating time (mean +/- SD) (36 +/- 9 minutes open
      vs. 37 +/- 7 minutes laparoscopic), perioperative mortality, degree of
      leukocytosis, fasting glucose, or C-reactive protein (p > 0.05). Nitrogen
      balance, wound scores, and tensile strength at 24 hours and 1 week were more
      favorable in the LA group than in the PA group (p < 0.05). In the cushingoid
      porcine model, laparoscopic adrenalectomy was less catabolic and was associated
      with fewer wound complications than the open posterior adrenalectomy. These
      findings provide support for continued pursuit of laparoscopic methods for
      adrenalectomy in the clinical setting.

PMID- 9597938
TI  - Subtotal adrenalectomy by the posterior retroperitoneoscopic approach.
AB  - The retroperitoneoscopic approach offers an established operative procedure for
      primary adrenal gland tumors. It allows a detailed view of the adrenal gland and
      its surrounding region. Therefore clear differentiation between normal and
      neoplastic adrenal tissue is sometimes possible, permitting a planned,
      unilateral, subtotal resection of the gland. Between July 1994 and August 1997
      primary benign adrenal gland tumors (11 Conn adenomas, 4 phenochromocytomas, 4
      Cushing adenomas, 3 hormonally inactive tumors; 2.4 +/- 1.2 cm in size; 8 on the
      right, 14 on the left) were removed from 22 patients by the posterior
      retroperitoneoscopic approach maintaining tumor-free portions of the ipsilateral
      adrenal gland. Two patients suffered from bilateral pheochromocytomas associated
      with multiple endocrine neoplasia (MEN-IIa) syndrome and had previously undergone
      complete adrenalectomy of the contralateral gland. Following subtotal resection
      the operating time and blood loss did not differ significantly (p > 0.05) from
      that seen with complete extirpation (46 patients operated during the same
      period). All patients with Conn adenomas and pheochromocytomas were biochemically
      and clinically cured (follow-up 11 months; range 1-31 months). The four patients
      with Cushing adenoma currently require decreasing cortisol substitution. In the
      two MEN-II patients adrenal gland cortical function could be maintained; one
      patient is on low-dose steroid supplementation and the other on none. No local
      recurrence of tumors has been observed. In selected cases the
      retroperitoneoscopically performed subtotal adrenal gland resection is a safe
      procedure that can potentially maintain the function of the adrenal gland cortex.

PMID- 9597939
TI  - Stage-dependent therapy of rectal carcinoid tumors.
AB  - Although malignant behavior of rectal carcinoid tumors is rare, the risk of
      metastases and death does exist. Adaptation of therapy according to the estimated
      malignancy seems necessary. To develop a stage-dependent therapy, 31 patients
      with rectal carcinoid tumors measuring 5 to 50 mm in diameter were analyzed
      retrospectively. Malignancy was estimated according to tumor size, infiltration
      depth, and histopathology. There were 18 tumors within the mucosa and submucosa
      (T1), 7 tumors with muscularis propria invasion (T2), and carcinoid tumor
      penetrating the full rectal wall (T3) or spreading to surrounding tissue (T4) in
      6 patients. Altogether 20 patients (65%) were treated with a minimally invasive
      intervention: endoscopic polypectomy (EP) in 12 and transanal excision (TE) in 8
      patients. In 11 patients (35%) aggressive surgical procedures--anterior resection
      (AR) in 4 and abdominoperineal resection (APR) in 7--were performed. After a mean
      +/- SD follow-up of 86.0 +/- 61.3 months, tumor recurrence was not seen in any of
      the 20 patients with minimally invasive treatment, and all were still alive. No
      severe complications associated with surgical procedures were detected. In
      contrast, 5 of the 10 patients with advanced tumor stage died from their disease
      despite aggressive surgery (AR, APR). In conclusion, depending on tumor stage,
      treatment of rectal carcinoids includes EP, TE, or extended resection. Minimally
      invasive techniques are safe treatments for small to medium-size T1/T2 rectal
      carcinoids. Extended surgery cannot improve the overall survival of those with
      advanced tumors (T3/T4, N1, M1) but can be beneficial for preventing local
      complications.

PMID- 9597940
TI  - Prospective study of calcium homeostasis after renal transplantation.
AB  - Nineteen consecutive patients receiving renal transplants underwent prospective
      evaluation of their calcium homeostasis for 1 year after transplantation to
      characterize indices of hyperparathyroidism (HPT) amelioration. All but one
      underwent dialysis, and six had vitamin D supplementation before grafting. The
      rapid falls in serum creatinine concentrations and increased creatinine
      clearances the first weeks after grafting were accompanied by rapidly reversed
      hypercalcemia and hypermagnesemia, induced hypophosphatemia, maintained
      parathyroid hormone (PTH) excess and calcitriol deficiency, and decreased
      alkaline phosphatases. At 3 months when the serum calcitriol had started to rise,
      serum PTH levels were the lowest and parathyroid responses to induced
      hypocalcemia the least abnormal. This was coupled to peaks in serum calcium, 24
      hour urine calcium excretions, and serum alkaline phosphatase levels. All
      patients had subnormal creatinine clearances at the study end, and normal serum
      PTH occurred in only seven of them. Arbitrary subgrouping of the material was
      performed according to posttransplant creatinine clearance and serum PTH levels.
      More satisfactory graft function related to lower serum PTH values and less
      abnormal parathyroid responses to induced hypocalcemia, earlier and higher rises
      in serum calcitriol, and higher urine calcium excretion. Patients with mild HPT
      at the study end generally had higher creatinine clearance, lower serum PTH,
      calcium, and alkaline phosphatase values, and lower urine calcium excretion.
      Moreover, they had fewer prevalent signs of radiologic bone involvement before
      grafting. These temporal diversities in conjunction with the variable graft
      function and intensity of immunosuppression provide a complex interaction in
      renal transplant recipients, which should be considered in the light of improved
      function of the PTH/PTHrP receptor in bone and kidney and cation receptors in the
      parathyroid and kidney.

PMID- 9597941
TI  - Triterpenoid saponins.

PMID- 9597942
TI  - Synthesis of 6-deoxyamino sugars.

PMID- 9597944
TI  - Indigenous people in a multicultural society: unique issues for human services.
AB  - Indigenous peoples have a unique place within a multicultural society. The
      history of indigenous people in the United States differs from those who came
      here as immigrants. For many Native Americans a primary goal has been self
      preservation through separation and isolation rather than seeking a place within
      a multicultural society. Many people are not aware that the federal government
      and some state governments have specific moral and legal rights and
      responsibilities toward Native Americans, unlike other groups in the United
      States. Human services providers who work with Native Americans must understand
      the issues specific to indigenous people in a multicultural society. This article
      examines the unique status of Native Americans in the United States and explores
      the practice implications of that status. The article begins with an overview of
      the components of culturally competent social work with Native Americans, then
      examines specific issues such as historical trauma and sovereignty with which
      social workers and other human services workers should be familiar to serve
      Native American clients effectively.

PMID- 9597943
TI  - Chemical warfare agents: estimating oral reference doses.
AB  - Health risk assessments for sites contaminated with chemical warfare agents
      require a comparison of the potential levels of exposure with a characterization
      of the toxic potency of each chemical. For noncancer health effects, toxic
      potency is expressed in terms of Reference Doses (RfD). A RfD is a daily exposure
      level or dose (usually expressed in units of milligrams of chemical per kilogram
      body weight per day) for the human population, including sensitive
      subpopulations, that is likely to be without an appreciable risk of deleterious
      effects. A daily exposure at or below the RfD is not likely to be associated with
      health risks, but as the amount of chemical that an individual is exposed to
      increases above the RfD, the probability that an adverse effect will occur also
      increases. A RfD is derived by first examining the available human or animal
      toxicity data to identify a dose or exposure that corresponds to a no-observed
      adverse-effect level (NOAEL) or a lowest-observed-adverse-effect level (LOAEL).
      The NOAEL is the exposure level at which there are no statistically or
      biologically significant increases in frequency or severity of adverse effects
      between the exposed population and its appropriate control. Effects may be
      produced at this level, but they are not considered to be adverse if they do not
      result in functional impairment or pathological lesions that affect the
      performance of the whole organism or which reduce an organism's ability to cope
      with additional challenge. The LOAEL is the lowest exposure level at which there
      are statistically or biologically significant increases in frequency or severity
      of adverse effects between the exposed population and its appropriate control. If
      only a LOAEL is identified by the toxicity data, a NOAEL is estimated by dividing
      the LOAEL by a factor no greater than 10. This extrapolation factor of 10 or less
      is termed the LOAEL-to-NOAEL Uncertainty Factor (UFL). The NOAEL is also adjusted
      by the application of other Uncertainty Factors, including (1) a UFH < or = 10 to
      ensure that the resulting RfD protects segments of the human population that may
      be more sensitive to the chemical than the average person; (2) a UFA < or = 10 to
      extrapolate from the experimental animal species to humans; (3) a UFS < or = 10
      to extrapolate from an experimental subchronic exposure study to a potential
      chronic exposure; and (4) a UFD < or = 10 to ensure that the resulting RfD is
      protective for all possible adverse effects, particularly those that may not have
      been adequately evaluated in the available studies. A Modifying Factor (MF),
      based on a qualitative professional assessment of the data, may also be used to
      account for other factors (e.g., deficiencies in the critical study) that are not
      adequately covered by the standard Uncertainty Factors. 1. Agent HD (Sulfur
      Mustard). RfDe = 7 x 10(-6) mg kg-1 d-1. A LOAEL was identified in a two
      generation reproductive toxicity study conducted in rats. A total uncertainty
      factor of 3000 was applied to account for protection of sensitive subpopulations
      (10), animal-to-human extrapolation (10), LOAEL-to-NOAEL extrapolation (3), and
      extrapolation from a subchronic to chronic exposure (10). A LOAEL-to-NOAEL UF of
      3, instead of the default value of 10, was used because the critical effect
      (stomach lesions) was considered to be "mild" in severity and may have been
      enhanced by the vehicle used (sesame oil in which sulfur mustard is fully
      soluble) and the route of administration (gavage), which is more likely to result
      in localized irritant effects. The key study did identify a toxic effect that is
      consistent with the vesicant properties of sulfur mustard. In none of the other
      available studies was there any indication of a different effect occurring at a
      lower exposure level.

PMID- 9597945
TI  - "Gathering the spirit" at First Baptist Church: spirituality as a protective
      factor in the lives of African American Children.
AB  - Knowledge of human behavior in cultural context is the source from which all
      ethnic-sensitive social work practice emerges. Although research on resilience
      has burgeoned over the past several decades, relatively little is known about
      socialization contexts and practices that support the development of African
      American children. This article summarizes an ethnographic study describing the
      beliefs of African American adults about children's socialization and related
      socialization practices within the context of Sunday school, and how this
      knowledge was used to generate an ethnic-sensitive social work intervention
      designed to support the development of resilience in African American children.

PMID- 9597946
TI  - School social workers and school violence: personal safety, training, and
      violence programs.
AB  - This article reports findings from a national survey that questioned school
      social workers on school violence. The article focuses on personal reports of
      victimization, precautions taken to avoid victimization, training needs to deal
      with school violence, programs in schools, and social workers' involvement with
      violence intervention. Findings suggest that many respondents believe social
      skills programs are not as effective as ecological interventions. Findings also
      indicate that the majority of school social workers have received school violence
      prevention training. These skills could be used in a national effort to reduce
      school violence. The authors recommend specific strategies for increasing the
      school social workers' role in school-based violence prevention efforts.

PMID- 9597948
TI  - Do sunscreens prevent skin cancer?

PMID- 9597947
TI  - Telephone support groups for HIV-positive mothers whose children have died of
      AIDS.

PMID- 9597950
TI  - Treating the gender bias of heart disease.

PMID- 9597949
TI  - Unraveling a mysterious cause of pain.

PMID- 9597951
TI  - Do you need a B12 boost?

PMID- 9597953
TI  - Can carpal tunnel syndrome be treated without surgery?

PMID- 9597952
TI  - Can chelation therapy cure heart disease?

PMID- 9597954
TI  - Is difficulty swallowing a normal sign of aging?

PMID- 9597955
TI  - Functional outcomes following treatment for advanced laryngeal cancer. Part I-
      Voice preservation in advanced laryngeal cancer. Part II--Laryngectomy
      rehabilitation: the state of the art in the VA System. Research Speech-Language
      Pathologists. Department of Veterans Affairs Laryngeal Cancer Study Group.
AB  - This two-part investigation assessed functional outcomes related to communication
      (including amount of speech therapy), swallowing and eating, and employment
      status for patients who received one of the two treatment modalities for advanced
      laryngeal cancer (stage III or IV laryngeal squamous cell carcinoma) in Veterans
      Administration Cooperative Study #268. One hundred sixty-six patients were
      randomized to primary surgery (laryngectomy) and radiotherapy (RT), and 166 to
      induction chemotherapy (CT) and RT. The first investigation dealt with examining
      and comparing functional outcomes for patients in the two treatment arms of the
      main study. Results showed clearly that patients with advanced laryngeal cancer
      are better off from the standpoint of speech communication if they can be treated
      for this disease without removal of the larynx. In contrast, there were few
      significant differences between patient groups for other non-speech-related
      measures. The second investigation focused on communication-related outcomes
      associated with the rehabilitation of total laryngectomy patients. Results
      revealed that only relatively small percentages of total laryngectomy patients
      (6%) developed usable esophageal speech or remained nonvocal (8%), and that a
      majority of patients ended up as users of artificial electrolarynx (55%) or
      tracheoesophageal (31%) speech. The results from both investigations are
      discussed with respect to factors that can influence the rehabilitation process
      and long-term outcome status of patients who are treated for advanced laryngeal
      cancer with these two strategies.

PMID- 9597956
TI  - AIDS in Africa.

PMID- 9597957
TI  - A side effect of protease inhibitors.

PMID- 9597958
TI  - Applause for Dr. Romalis.

PMID- 9597959
TI  - Advance directives for insulin-using diabetic patients.

PMID- 9597960
TI  - Breast cancer guidelines.

PMID- 9597961
TI  - Breast cancer guidelines.

PMID- 9597962
TI  - Updating the insulin lispro file.

PMID- 9597963
TI  - In defence of the military.

PMID- 9597964
TI  - Coronary artery bypass graft surgery in Newfoundland and Labrador.
AB  - BACKGROUND: Newfoundland and Labrador, like other health care jurisdictions, is
      faced with widening gaps between the demands for health care and a strained
      ability to supply the necessary resources. The authors carried out a study to
      determine the rates of appropriate and inappropriate coronary artery bypass
      grafting (CABG) in the province and the waiting times for this surgery. METHODS:
      This retrospective cohort study was performed in the tertiary care hospital that
      receives all referrals for coronary angiography and coronary artery
      revascularization for Newfoundland and Labrador. By reviewing the hospital
      records, the authors identified 2 groups of patients: those in whom critical
      coronary artery disease was diagnosed on the basis of coronary angiography and
      who were referred for CABG between Apr. 1, 1994, and Mar. 31, 1995, and those who
      actually underwent the procedure during that period. By applying specific
      criteria developed by the RAND Corporation, the authors determined the
      appropriateness and necessity of CABG in each case. They also compared waiting
      times for CABG with optimal waiting times; as determined by a consensus-based
      priority score. RESULTS: A total of 338 patients underwent CABG during the study
      period. The cases were characterized by multivessel disease and late-stage angina
      symptoms. Almost all of the patients had high appropriateness scores (7-9), and
      nearly 95% had high necessity scores (7-9). However, during the study period, the
      waiting list increased by about 20%, because a total of 391 patients were
      referred by the weekly cardiovascular surgery conference; the authors identified
      these and an additional 31 patients as having necessity scores of 7 or more. Only
      7 (23%) of 31 patients for whom CABG was considered very urgent underwent surgery
      within the recommended 24 hours, and only 30 (24%) of the 122 patients for whom
      CABG was considered urgent underwent surgery within the recommended 72 hours.
      INTERPRETATION: These results provide evidence that the cardiac surgery program
      in Newfoundland and Labrador is performing CABG in patients for whom surgical
      revascularization is highly appropriate and necessary. Access to CABG is less
      than ideal, however, since the waiting list continues to expand, and many
      patients wait beyond the recommended time for surgery.

PMID- 9597965
TI  - Food bank users: sociodemographic and nutritional characteristics.
AB  - BACKGROUND: The continued expansion of food assistance programs makes it
      important to examine the sociodemographic characteristics and nutritional
      profiles of people relying on this service. The authors undertook such a study in
      a large urban centre. METHODS: A total of 490 food bank users were randomly
      selected from a stratified random sample of 57 urban food banks in Montreal. A
      questionnaire and a dietary recall interview were given by a dietitian
      interviewer to determine socioeconomic, demographic and cultural characteristics
      and macronutrient intake. These data were compared with national and provincial
      data. RESULTS: The mean age of the participants (256 men and 234 women) was 41
      years; 204 (41.6%) were living alone and most (409 [83.5%]) were receiving social
      assistance benefits. These food bank users were well educated (190 [38.8%] had
      completed technical school or had a college or university education), and the
      sample included few elderly or disabled people. The median body mass index was
      greater than 24, which indicated that energy intake, although below recommended
      levels, was not a chronic problem. The people using the food banks had a monthly
      shortfall in their food budget of between $43 and $46. INTERPRETATION: Food banks
      are used regularly, primarily by young healthy adults. They are though of as a
      necessary community resource.

PMID- 9597966
TI  - Benchmarking the provision of coronary artery surgery.

PMID- 9597967
TI  - Unconventional therapies for cancer: 3. Iscador. Task Force on Alternative
      Therapies of the Canadian Breast Cancer Research Initiative.

PMID- 9597968
TI  - Wrestling hyperthermia and dehydration.

PMID- 9597969
TI  - Hemophilia society warns MDs: bleeding disorders not a male domain.

PMID- 9597970
TI  - Secondhand-smoke story goes up in flames.

PMID- 9597971
TI  - Cameras becoming ER physicians', courts' allies.

PMID- 9597972
TI  - Dr. Jon Gerrard's attention switches from federal cabinet to evidence-based child
      care.
AB  - Dr. Jon Gerrard, a Winnipeg pediatrician who went from the heights of political
      success with a post in the federal cabinet to a narrow defeat in the 1997 federal
      election, is now devoting his attention to improving health care for children. He
      thinks the internet can play a lead role in these improvements.

PMID- 9597973
TI  - Brother, can you spare $1,000,000?

PMID- 9597974
TI  - Physician health and well-being.
AB  - Physicians should strive to manage professional and personal stress to maintain
      their own health and well-being and to maximize their ability to provide quality
      health care to their patients. This policy outlines strategies and
      recommendations that address a range of health and well-being issues throughout
      the physician life cycle. Implementation requires commitment and action by many
      individuals and groups, including medical students, residents and practising
      physicians; governments, regional authorities and decision-makers in health care
      facilities; medical school deans, faculty, and undergraduate and postgraduate
      program directors; and those representing national, provincial and territorial
      medical organizations.

PMID- 9597975
TI  - Tell your patients to take a walk.

PMID- 9597976
TI  - Geriatrics photo quiz. Acromegaly, an endocrine disorder.

PMID- 9597977
TI  - Scaly papules on the face and hands. Actinic keratoses.

PMID- 9597978
TI  - Tremor: how to determine if the patient has Parkinson's disease.
AB  - Tremor is commonly the first neurologic sign of Parkinson's disease (PD) that
      leads patients to see a physician. Knowing how to differentiate the resting
      tremor of PD from essential tremor is an important diagnostic skill. Unlike
      patients with essential tremor, those with PD have other neurologic findings. A
      diagnosis of PD is likely if the patient has two of three major clinical
      features: resting tremor, bradykinesia, and rigidity. Minor signs may also be
      seen, including cognitive slowing, speech abnormalities, depression,
      dysautonomia, and sleep disturbances. The history and physical exam can determine
      if the patient has parkinsonism and whether the cause is Parkinson's disease.

PMID- 9597979
TI  - Medical treatment of essential tremor and Parkinson's disease.
AB  - Although there is no known cure for essential tremor or Parkinson's disease (PD),
      medical treatment can often significantly reduce or eliminate functional
      disability. Mild essential tremor does not require treatment, and early treatment
      does not arrest or slow the natural progression in symptoms. When essential
      tremor interferes with daily activities, medical treatment options include beta
      blockers, anticonvulsants, benzodiazepines, and carbonic anhydrase inhibitors.
      Because of the great variability in the presentation of PD, no single approach is
      appropriate for all patients. Levodopa is the mainstay of pharmacologic therapy
      for PD, although other agents are indicated for monotherapy or in combination
      with levodopa. These include traditional and newer dopamine agonists, amantadine,
      anticholinergics, selegiline, and an emerging class of agents called COMT
      inhibitors.

PMID- 9597980
TI  - Type 2 diabetes: patient education and home blood glucose monitoring. 3.
AB  - Successful treatment of type 2 diabetes requires the interaction of the patient,
      his or her family, and a variety of healthcare professionals. Education is the
      most powerful tool doctors have to convince patients, especially those who are
      asymptomatic, of the serious complications that can result from uncontrolled
      diabetes. Home blood glucose monitoring is a key to the doctor-patient
      partnership. Physicians may have to consider a patient's cultural and dietary
      customs in developing a manageable program of weight loss, diet, and physical
      activity, the most effective forms of treatment. Referrals should be made to
      local diabetes organizations with patient support programs, when available.
      Patient empowerment and education are key to effective management.

PMID- 9597982
TI  - Wound repair in older patients: preventing problems and managing the healing.
      Interview by Marc E. Weksler.
AB  - Because advanced age is associated with delayed wound healing and repair,
      prevention remains the cornerstone of wound care in the older population. Healing
      is complicated by the increased prevalence in older patients of conditions that
      predispose them to pressure ulcers, such as malnutrition, immobility, and
      systemic disease. If preventive measures fail, there are treatments available to
      minimize surface contact at pressure points and therapeutic agents to promote
      wound healing. These treatment approaches include topical dressings that create
      an optimal healing environment, specially designed support surfaces, and growth
      factor topicals that can increase the proliferation, migration, and protein
      biosynthesis of cells in the wound bed.

PMID- 9597981
TI  - Cooperative health care clinics: a group approach to individual care.
AB  - In cooperative health care clinics (CHCC), health care is provided to older
      patients in a group setting. The CHCC concept, which was developed under a
      research grant by Kaiser Permanente in Colorado in 1991, showed improvement in
      patient and provider satisfaction, as well as improved quality of care and cost
      effectiveness. CHCC are being replicated in other sites under a research grant
      from the Robert Wood Johnson Foundation. In addition to formal findings from
      research studies, much has been learned about factors that have promoted the
      success of the program.

PMID- 9597984
TI  - Appropriate follow-up of patients with colon cancer.

PMID- 9597985
TI  - Chest radiography in children with acute lower respiratory infection.

PMID- 9597986
TI  - The patient's differential diagnosis.

PMID- 9597987
TI  - Donepezil for Alzheimer's disease.

PMID- 9597988
TI  - Rectal exam during routine pelvic exam.

PMID- 9597989
TI  - Estimating fetal weight.

PMID- 9597990
TI  - Warfarin and aspirin for prevention of IHD.

PMID- 9597991
TI  - What do we know about wellness programs?

PMID- 9597992
TI  - New knowledge, new tools: a look inside the 'black box' of family practice.

PMID- 9597993
TI  - The value of a family physician.
AB  - BACKGROUND: Most efforts to improve health care have been made without a full
      understanding of the value of a primary care approach. METHODS: This article
      synthesizes the observations from the Direct Observation of Primary Care (DOPC)
      study. This multimethod study of 138 family physicians in 84 practices included
      direct observation of 4454 patients visits were used to describe aspects of
      family practice that may provide value for patients. RESULTS: Family physicians
      provide and coordinate care for a wide variety of patients problems, prioritizing
      these competing demands on the basis of relationships developed during multiple
      patient visits over time. They use acute and chronic illness visits as
      opportunities to integrate care for specific diseases, mental health, and
      preventive care in ways that are tailored to the specific needs of patients and
      families. Higher rates of delivery of core attributes of family practice are
      associated with patient satisfaction and preventive services delivery, and are
      diminished by forced discontinuity of care. CONCLUSIONS: Family physicians
      prioritize and deliver care according to a broad agenda based on patient needs.
      These needs are understood within ongoing relationships with the patient, family,
      larger health care system, and community. This integrative approach includes
      numerous avenues for affecting important patient outcomes that are unlikely to be
      optimally met by less integrated models of medical care. Expanding the value of
      family practice will require the development and application of new knowledge of
      the core structures, processes, and contexts of family practice, and their
      effects on patient outcomes.

PMID- 9597994
TI  - Understanding change in primary care practice using complexity theory.
AB  - BACKGROUND: Understanding the organization of primary care practices is essential
      for implementing changes related to delivery of preventive or other health care
      services. A theoretical model derived from complexity theory provides a framework
      for understanding practice change. METHODS: Data were reviewed from brief
      participant observation fieldnotes collected in the 84 practices of the Direct
      Observation of Primary Care (DOPC) study and in 27 practices from three similar
      studies investigating preventive services delivery. These data were synthesized
      with information from an extensive search of the social science, nursing, and
      health services literature concerning practice organization, and of the
      literature on complexity theory from the fields of mathematics, physics, biology,
      management, medicine, and family systems, to create a complexity model of primary
      care practice. RESULTS: Primary care practices are understood as complex adaptive
      systems consisting of agents, such as patients, office staff, and physicians, who
      enact internal models of income generation, patient care, and organizational
      operations. These internal models interact dynamically to create each unique
      practice. The particular shape of each practice is determined by its primary
      goals. The model suggests three strategies for promoting change in practice and
      practitioner behavior: joining, transforming, and learning. CONCLUSIONS: This
      model has important implications for understanding change in primary care
      practice. Practices are much more complex than present strategies for change
      assume. The complexity model identified why some strategies work in particular
      practices and others do not.

PMID- 9597995
TI  - Illuminating the 'black box'. A description of 4454 patient visits to 138 family
      physicians.
AB  - BACKGROUND: The content and context of family practice outpatient visits have
      never been fully described, leaving many aspects of family practice in a "black
      box," unseen by policymakers and understood only in isolation. This article
      describes community family practices, physicians, patients, and outpatient
      visits. METHODS: Practicing family physicians in northeast Ohio were invited to
      participate in a multimethod study of the content of primary care practice.
      Research nurses directly observed consecutive patient visits, and collected
      additional data using medical record reviews, patient and physician
      questionnaires, billing data, practice environment checklists, and ethnographic
      fieldnotes. RESULTS: Visits by 4454 patients seeing 138 physicians in 84
      practices were observed. Outpatient visits to family physicians encompassed a
      wide variety of patients, problems, and levels of complexity. The average patient
      paid 4.3 visits to the practice within the past year. The mean visit duration was
      10 minutes. Fifty-eight percent of visits were for acute illness, 24% for chronic
      illness, and 12% for well care. The most common uses of time were history-taking,
      planning treatment, physical examination, health education, feedback, family
      information, chatting, structuring the interaction, and patient questions.
      CONCLUSIONS: Family practice and patient visits are complex, with competing
      demands and opportunities to address a wide range of problems of individuals and
      families over time and at various stages of health and illness. Multimethod
      research in practice settings can identify ways to enhance the competing
      opportunities of family practice to improve the health of their patients.

PMID- 9597996
TI  - The family in family practice: is it a reality?
AB  - BACKGROUND: The purpose of this study was to describe, from multiple
      perspectives, the extent to which community family physicians focus on the
      family. METHODS: In a cross-sectional study, research nurses directly observed
      consecutive patient visits for 2 days in the offices of 138 community family
      physicians. Data were collected on 4454 outpatient visits using direct
      observation, patient and physician questionnaires, and medical record review.
      Descriptive statistics were calculated, and a factor analysis was used to
      identify subsets of correlated family focus descriptors. RESULTS: On average, 10%
      of the time intervals during patient visits was devoted to addressing family
      issues. Other family members were present during 32% of visits, and another
      family member's problems were discussed in 18% of visits. Seventy percent of
      patients reported that other family members see the same doctor. A family history
      was obtained during 51% of visits by new patients and 22% of visits by
      established patients. Genograms were present on 11% of charts and family folders
      were seldom used. The presence or absence of a family history of breast or colon
      cancer was noted in 40% of charts. A factor analysis identified two different
      physician styles: family history as a context for care of an individual patient,
      and the family as the unit of care. The latter approach correlated with the
      patient's assessment that the doctor knew their families. CONCLUSIONS: Family
      physicians show a high degree of emphasis on the family, and exhibit two
      different styles of family focus in community practice. The effects of these
      different approaches to family care on patient outcomes is an important area for
      future research.

PMID- 9597997
TI  - Trade-offs in high-volume primary care practice.
AB  - BACKGROUND: With today's emphasis on reducing costs and increasing efficiency,
      primary care physicians are under pressure to increase patient volume. This study
      was undertaken to (1) identify factors associated with differences in physician
      volume, and (2) test for differences in selected clinical outcomes and time use
      during patient visits. METHODS: Research nurses directly observed consecutive
      patient visits during 2 separate days in the offices of 108 community family
      physicians. Data on the content of 3893 outpatient visits were collected using
      direct observation, patient and physician questionnaires, and medical record
      review. Physicians with high-, medium-, and low-volume practices were compared in
      the rates of preventive services delivery, patient satisfaction, and time use
      during patient visits as measured with the Davis Observation Code. RESULTS: High
      volume physicians had visits that were 30% shorter, scheduled one third fewer
      patients for well care, and were more likely to own their practice and to be male
      than were low-volume physicians. Time use during patient visits was remarkably
      similar for high- and low-volume physicians. However, after controlling for
      relevant patient characteristics, patients of high-volume physicians had lower up
      to-date rates of preventive services and scored lower on measures of satisfaction
      and the doctor-patient relationship. CONCLUSIONS: Physicians with high-volume
      practices are more efficient than those with low-volume practices in providing
      similar services in a shorter amount of time. This greater apparent efficiency
      may come at a cost of lower rates of preventive services delivery, lower patient
      satisfaction, and a less positive doctor-patient relationship. Health care plans
      and physicians setting productivity goals should consider the trade-offs inherent
      in high-volume practice.

PMID- 9597998
TI  - Primary care practice organization and preventive services delivery: a
      qualitative analysis.
AB  - BACKGROUND: Rapid developments within the health care environment have led to
      increased pressures for change among primary care physicians and their practices.
      Nevertheless, a lack of understanding of practice organization and function has
      limited the effectiveness of attempts to change practice behaviors. Recent
      attempts to increase the delivery of preventive health care services illustrate
      the limitations of current approaches. To assist physicians in their attempts at
      change, our study looked at the office as a whole system and at the competing
      demands within the primary care setting. METHODS: Qualitative fieldnotes were
      recorded by research nurses who observed 138 family physicians in 84 practices in
      northeast Ohio for 4 days each. These data were content-analyzed to identify
      features that are important for understanding how practices are organized.
      RESULTS: These data indicate that primary care practice is much more complex than
      research and transformation efforts generally acknowledge. The data identified a
      diverse set of features that describe how primary care practices are organized
      and function. These included cognitive and behavioral components of physician
      philosophy and style, and numerous features of the practice organization, such as
      office efficiency, clarity of staff roles, communication patterns among
      physicians and staff, and approaches to using office protocols. The data also
      suggest that some practices are more innovative than others and that some
      physicians or staff have special motivations that can support or inhibit a
      particular change. CONCLUSIONS: Physicians who want to change their practice, as
      well as those persons who want to stimulate change from the outside, need to have
      a more comprehensive approach than is now commonly used to assess practices that
      encompass a broad spectrum of variables.

PMID- 9597999
TI  - The impact of recent emotional distress and diagnosis of depression or anxiety on
      the physician-patient encounter in family practice.
AB  - BACKGROUND: Primary care physicians are expected to identify mental health
      problems. Currently, it is unclear how a recent experience of emotional distress
      affects the physician-patient encounter and the diagnostic process. METHODS:
      Using the Davis Observation Code, we studied 1269 encounters between family
      physicians and adult patients who completed brief questionnaires after the visit.
      Patients were separated into three groups using self-report and billing data:
      those denying recent emotional distress, those reporting recent emotional
      distress but not receiving a mental health diagnosis, and those reporting recent
      emotional distress and receiving a diagnosis of anxiety or depression. RESULTS:
      Nineteen percent of patients reported significant emotional distress during the
      previous 4 weeks; 18% of these patients received a billing diagnosis of
      depression or anxiety. Patients not reporting emotional distress had the shortest
      visits (10.0 minutes); recent emotional distress was associated with
      significantly longer visits: 11.5 minutes for those without a diagnosis of
      depression or anxiety and 12.8 minutes for those with a diagnosis of depression
      or anxiety. The visits of patients with a diagnosis of depression or anxiety
      included more counseling, history-taking, and discussions of family information
      and substance use, and less time providing physical examination and evaluation
      feedback. Fewer preventive services and less chatting occurred when patients
      reported recent distress, regardless of diagnosis. CONCLUSIONS: Recent patient
      emotional distress has a powerful impact on the structure of the family practice
      visit, with important implications for efforts to enhance diagnosis and treatment
      of mental health issues. The challenge for the family physician is to recognize
      and treat a patient's emotional distress while continuing to fulfill competing
      medical demands.

PMID- 9598000
TI  - Opportunistic preventive services delivery. Are time limitations and patient
      satisfaction barriers?
AB  - BACKGROUND: The use of illness visits as opportunities to increase the delivery
      of preventive services has been widely recommended, but its feasibility in
      community practice is not known. We examined the prevalence of this opportunistic
      approach to providing preventive services, and the degree to which patient
      satisfaction and time limitation are barriers. METHODS: Consecutive patient
      illness visits to 138 community family physicians were directly observed. Visits
      by patients who received at least one preventive service recommended by the US
      Preventive Services Task Force were compared with visits by patients not
      receiving any recommended preventive services, controlling for potentially
      confounding patient characteristics. RESULTS: Among 3547 illness visits,
      preventive services were delivered during 39% of visits for chronic illness and
      30% of visits for acute illness. Opportunistic health habits counseling occurred
      more frequently than screening or immunization. Visit satisfaction reported by
      2454 patients using the Medical Outcomes Survey 9-item Visit Rating Scale was not
      different during illness visits with or without the delivery of preventive
      services. The duration of illness visits that included preventive services was an
      average of 2.1 minutes longer than illness visits without such interventions (95%
      confidence interval, 1.7-2.4). CONCLUSIONS: The delivery of preventive services
      during illness visits is common in community practice and is well accepted by
      patients. The expansion of an opportunistic approach to providing preventive
      services will require attention to time-efficient approaches.

PMID- 9598001
TI  - Making time for tobacco cessation counseling.
AB  - BACKGROUND: The objective of this study was to examine the incidence, targeting,
      and time demands of tobacco cessation advice by community family physicians.
      METHODS: Research nurses directly observed 2 days of outpatient visits to 138
      family physicians in northeast Ohio. Smoking status was identified by patient
      questionnaire. Visit characteristics were determined from direct observation and
      billing data. Visits by smokers with and without smoking cessation advice were
      compared. RESULTS: The incidence of tobacco cessation advice was highest during
      wellness visits (55% vs 22% for illness visits; P < .001). Smokers seen for a
      tobacco-related chronic illness were more likely to receive advice than those
      seen for a chronic problem not related to tobacco (32% vs 17%; P = .05). The
      average duration of advice was less than 1 1/2 minutes. There were no significant
      differences in the duration of advice across different types of visits.
      CONCLUSIONS: Physicians are providing brief, targeted interventions for smoking
      cessation in family practices. The findings support the feasibility of
      implementing a brief intervention with all smokers seen during office visits.

PMID- 9598002
TI  - The effect of a secondary patient on the family practice visit.
AB  - BACKGROUND: This study describes how the provision of care to a family member
      other than the identified patient affects the outpatient family practice visit.
      METHODS: Research nurses directly observed consecutive patient visits on 2
      separate days in the offices of 138 practicing family physicians. Patient visits
      during which another family member's problem was addressed were identified.
      Differences in patient and visit characteristics, patient satisfaction, delivery
      of preventive services, and time use, measured with the Davis Observation Code,
      were compared for visits with and without the provision of care to a family
      member. RESULTS: Care was provided to a secondary patient during 18% of observed
      outpatient visits. The secondary patient was present during only half of these
      visits. When another family member's problem was discussed, patients were more
      likely to report that their expectations for the visit were met. There was no
      difference in patient report of satisfaction with the visit, the delivery of
      preventive services, or the level of billing for visits at which another family
      member's problem was addressed. Visits during which another family member's
      problem was discussed were an average of 1.3 minutes longer; with less time spent
      chatting, providing feedback, and conducting physical examinations, and more time
      spent counseling, taking history, gathering family information, and delivering
      preventive services. CONCLUSIONS: The provision of care to a second family member
      is relatively common in family practice, and affects the care of the index
      patient in identifiable ways. This care of another family member represents an
      important added value of family practice.

PMID- 9598003
TI  - Autologous human collagen and dermal fibroblasts for soft tissue augmentation.
AB  - BACKGROUND: Augmentation of soft tissue defects can be achieved through
      intradermal injection of silicone, animal collagen, plasma-gelatin mixture, and
      fat. Due to their rapid degradation in vivo, however, clinical effects are
      typically transient. The use of autologous human collagen could conceivably
      result in sustained clinical improvement due to decreased collagen degradation.
      OBJECTIVE: The purpose of this study was to determine whether prolonged dermal
      correction could be achieved through injection of autologous human fibroblasts.
      RESULTS: Significant sustained clinical improvement was observed in two of the
      original 12 patients entered into the study. The nasolabial fold region was shown
      to be the most responsive facial area to treatment. CONCLUSIONS: The use of
      injectable autologous human collagen for soft tissue correction remains an
      intriguing prospect. While the findings of this study indicate possible sustained
      clinical improvement using this autologous system in some patients, it remains
      difficult to predict the degree and duration of individual response in various
      areas.

PMID- 9598004
TI  - Carbon dioxide laser resurfacing of peri-oral rhytids in scleroderma patients.
AB  - BACKGROUND: The short pulse duration high-energy carbon dioxide (CO2) lasers have
      been used in the past for treating cutaneous pathology and more recently for
      cosmetic improvements of rhytids, photo-aging, and acne. OBJECTIVE: This study
      was undertaken to determine the benefits of CO2 laser resurfacing on the severe
      peri-oral rhytidosis commonly seen in patients with systemic scleroderma.
      METHODS: Three patients were studied and evaluated for satisfactory wound
      healing, improved cosmetic result, and lack of complications. RESULTS: All three
      patients experienced significant improvement following laser resurfacing.
      CONCLUSION: The study demonstrated the safe and effective treatment for peri-oral
      rhytidosis in patients with generalized scleroderma utilizing CO2 laser
      resurfacing.

PMID- 9598005
TI  - Facial hypertrophic scarring from pulsed dye laser.
AB  - BACKGROUND: The 585-nm, 450-msec pulsed dye laser is widely used to treat benign
      vascular lesions. The biophysical interactive properties of this laser allow
      effective, precise small vessel ablation with very low incidence of pigmentary
      alteration and atrophic scarring side effects. OBJECTIVE: We are reporting a case
      of hypertrophic scar development on the upper lip of a patient whose facial
      hypertrophic port-wine stain was treated by pulsed dye laser. METHODS: The most
      effective energy fluence was determined by analysis of test areas treated at
      various fluences. This fluence was used for the initial full lesion treatment,
      with subsequent fluences chosen by treatment response at each 4-week follow-up
      visit. RESULTS: After the fourth treatment a hypertrophic scar developed on our
      patient's left cutaneous upper lip. CONCLUSIONS: This hypertrophic scar developed
      after pulsed dye laser treatment because the patient did not follow posttreatment
      care instructions, and because the initial treatment fluences of 8.0-8.5 J/cm2
      may have been too high.

PMID- 9598006
TI  - Concurrent use of laser skin resurfacing and punch excision in the treatment of
      facial acne scarring.
AB  - BACKGROUND: Laser skin resurfacing has added to the numerous treatment options
      available for acne scarring. Adjunct modalities such as punch excision should be
      considered to enhance treatment outcomes. Traditionally, punch excision and
      grafting have been performed, followed 1-2 months later by dermabrasion.
      OBJECTIVE: To determine the effectiveness of laser skin resurfacing and the
      concurrent use of punch excision performed at the same treatment session in the
      treatment of acne scarring. METHODS: Twenty-one patients with skin types I-III
      with mild to severe facial acne scarring were treated with a combination of laser
      skin resurfacing and punch excision of acne scars in the same treatment session.
      Baseline, postoperative, and follow-up photographs were taken and evaluated by an
      independent dermatologist and a laser nurse blinded to patient treatment. In
      addition, subjective patient assessments of improvement were obtained. RESULTS:
      There was a range of clinical improvement by the independent assessor of 25-50%
      in skin type I, 50-75% in skin type II, and 50-75% in skin type III. There was a
      patient subjective improvement of 25-50% for skin type I, 50-75% for skin type II
      and 75-100% for skin type III. Postoperative hyperpigmentation was noted in five
      patients and postoperative hypopigmentation was not seen in any patients. There
      was no wound dehiscence, evidence of infection, or hypertrophic scarring of
      treated areas noted on follow-up. CONCLUSION: Laser skin resurfacing with the
      concurrent use of punch excision improves facial acne scarring. This newly
      described method negates the need to delay additional resurfacing for a future
      visit.

PMID- 9598007
TI  - Pulsed dye laser treatment of molluscum contagiosum in a patient with acquired
      immunodeficiency syndrome.
AB  - BACKGROUND: Molluscum contagiosum is usually a self-limited benign viral disease
      in children and young adults. In patients with acquired immunodeficiency syndrome
      (AIDS), however, the infection is often widespread, disfiguring, and recalcitrant
      to conventional therapy. OBJECTIVE: A treatment modality for widespread,
      recurrent molluscum contagiosum is necessary that is effective, safe, and simple.
      METHODS: Widespread molluscum contagiosum recalcitrant to conventional therapy in
      a patient with AIDS was treated with the 585-nm pulsed dye laser. RESULTS: There
      was a significant reduction in the number of molluscum contagiosum lesions
      following a single treatment with the pulsed dye laser. Treated-areas remained
      disease-free after 4 months. No complications were associated with the procedure.
      CONCLUSION: Pulsed dye laser treatment may offer another therapeutic modality
      that is effective and safe in the treatment of widespread and recurrent molluscum
      contagiosum.

PMID- 9598009
TI  - Cosmetics, skin care products, and the dermatologic surgeon. Postsurgical
      selection of cleansing products.
AB  - Postsurgical care is almost as important as the skill of the dermatologic surgeon
      in ensuring the patient a good result. Scientifically based cleansing product
      selection and careful patient cleansing instructions are necessary to optimize
      healing while meeting patient hygiene needs.

PMID- 9598008
TI  - Comparison of skin anesthetic effect of liposomal lidocaine, nonliposomal
      lidocaine, and EMLA using 30-minute application time.
AB  - BACKGROUND: Liposomes are microscopic phospholipid vessels that have been
      utilized to extend the action of topical medications. Previous studies have
      demonstrated that liposomal vehicles can prolong the action of a variety of
      medications, including antifungals, anesthetics, interferon, and antineoplastic
      agents. OBJECTIVE: The purpose of this study was to examine the degree and
      duration of anesthesia produced by lidocaine in a liposomal vehicle compared with
      lidocaine in a nonliposomal vehicle and compared with EMLA. The topical
      preparations in this study were allowed to contact the skin for a 30-minute
      period prior to evaluation of anesthetic effectiveness. Unoccluded and Tegaderm
      occluded topical preparations were evaluated in two separate arms of the study.
      MATERIALS AND METHODS: Thirteen healthy volunteers (three male, 10 female) were
      recruited for the nonocclusion arm of the study. Six healthy volunteers (two
      male, four female) were recruited for the occlusion arm of the study. Subjects
      with a history of allergy to lidocaine, a history of seizures, cardiac or
      respiratory difficulty, pregnant patients, and patients less than 18 years old
      were excluded. Written informed consent was obtained from all patients prior to
      testing. The volar forearms of the volunteers were swabbed with isopropyl alcohol
      and allowed to dry. A template was then utilized to mark 2 x 2-cm squares with a
      skin marker on both volar forearms. In total, nine squares corresponding to nine
      test areas were marked. The nine test preparations were applied to the test areas
      in a double-blinded fashion using a clean swab stick. The test preparations were
      then allowed to remain on the skin for 30 minutes in either occluded or
      nonoccluded from depending upon the arm of the study. Following the 30-minute
      application period, the test preparations were wiped off with clean gauze.
      Testing for anesthesia was performed by following a previously published method
      utilizing gentle pinpricks. A new pinprick apparatus was used for each patient.
      Pinprick testing was performed at 0, 15, 30, 60, and 90 minutes following the end
      of the 30-minute application period. Patients' responses to the pinprick were
      recorded in a binary fashion, as being either: 1) totally painless or 0)
      painfully sharp to any degree. Ten applications of the pinprick were applied
      randomly across each 2 x 2-cm test area. The number of painless applications of
      the pinprick out of a total of 10 applications of the pinprick was then recorded
      for each test area at every particular test time. In total, nine test
      preparations were evaluated. Analysis of the data was performed by a PhD
      statistical faculty consultant from the UCLA Mathematics Department. RESULTS:
      Liposomal lidocaine preparations evidenced longer durations of anesthesia than
      lidocaine preparations in nonliposomal vehicles. Five percent liposomal lidocaine
      preparations were statistically equivalent to EMLA in anesthetic effectiveness.
      CONCLUSION: Five percent liposomal lidocaine is an effective alternative topical
      agent for use in the attainment of temporary local anesthesia of the skin.

PMID- 9598010
TI  - Aplasia cutis congenita of the scalp. Report of 16 cases.
AB  - BACKGROUND: Aplasia cutis congenita (CCA) is a rare developmental anomaly. Its
      etiology and pathogenesis remain unclear. There are several hypotheses as to the
      influence of genetic and external factors on the fetus. Terminology of this
      anomaly is still a subject of discussion. OBJECTIVES: This paper describes 16
      patients with CCA of the scalp, ranging in age from 3 to 15 years, observed over
      the period of 15 years. Among them, girls prevailed 9:7. CCA was more common on
      the vertex rather then in the temporal region 13:3. In one girl multiple
      malformations were observed. METHODS: Location, shape, and size of the lesion
      determined as CCA were analyzed. Detailed history was taken and cytogenetic
      examination was performed to reveal etiopathogenetic factors. Treatment consisted
      of excision of the lesion and reconstruction of the scalp with neighboring skin
      flaps. The excised lesion underwent histologic examination. RESULTS: No
      etiopathogenetic factors were found. Histopathologic examinations indicate that
      the observed congenital scalp anomalies resemble a scar. Surgical treatment
      produced good cosmetic results. CONCLUSIONS: Literature on CCA will facilitate
      physicians to make the right diagnosis. Further accumulation of detailed
      descriptions on CCA patients may contribute to recognition of etiopathogenesis of
      this anomaly.

PMID- 9598012
TI  - Burn scar carcinoma. Diagnosis and management.
AB  - BACKGROUND: The term Marjolin ulcer is now synonymous with malignant
      transformation of chronic ulcers, sinus tracts, and burn scars. OBJECTIVE: To
      illustrate the importance of incisional or excisional biopsies in cases of
      suspected burn scar carcinoma. METHODS: Case report and review of the literature.
      RESULTS: Multiple punch biopsies were negative while a complete excision revealed
      the diagnosis of squamous cell carcinoma. CONCLUSION: Because of the focal nature
      of malignant change in burn scars, incisional or excisional biopsy should be
      performed.

PMID- 9598011
TI  - Abnormal expression of epiligrin and alpha 6 beta 4 integrin in basal cell
      carcinoma.
AB  - BACKGROUND: Basal cell carcinoma is characterized by local invasion, and only
      rarely metastasizes. The role of the containing basement membrane (BM) in this
      tumor is unclear. Several BM components have been shown to be absent or
      significantly reduced in BM surrounding infiltrating tumor. OBJECTIVE: The
      purpose of this study is to examine the expression of epiligrin, a BM-associated
      glycoprotein, and the integrin chains alpha 3, alpha 6, beta 1, and beta 4 in the
      basement membranes surrounding basal cell carcinoma. METHODS: Samples were
      obtained from 20 patients with basal cell carcinomas and subjected to a standard
      avidin biotin complex/alkaline phosphatase immunohistochemical technique using a
      panel of antibodies. RESULTS: There was a consistent abnormality of expression of
      epiligrin, alpha 6, and beta 4. CONCLUSION: We propose that reduced expression of
      epiligrin is involved in the pathogenesis of the local invasion by tumor and that
      an altered integrin ratio in basal cell carcinoma enhances tumor spread.

PMID- 9598013
TI  - A novel occlusive dressing for skin resurfacing.
AB  - BACKGROUND: Over the last decade the benefits of occlusive dressings have been
      appreciated. These dressings allow the epithelium to resurface easier. The wound
      heals quicker. OBJECTIVE: To evaluate a new silicone sheeting for immediate post
      op wound care. Our objective was to determine its benefit in the wound care
      management after laser skin resurfacing. METHOD: The silicone sheeting was
      applied immediately after laser resurfacing in 35 individuals. This temporary
      skin replacement was held in place with 4 x 4 gauzes and tube gauze netting.
      Although the tube netting and the 4 x 4 gauzes were changed daily the silicone
      sheeting remained in place for 4 or 5 days. Following this, applications of a
      petrolatum-based ointment were continued for another 5 days. At day 10 the skin
      care program was changed to a moisturizing sunscreen. Bleaching cream was added
      at day 15 in darker complexed individuals. RESULTS: The dressing accelerated
      wound healing. Pain and swelling were minimized under the sheeting. Histologic
      examinations demonstrated a more rapid reepithelialization at these treated
      sites. Other than technical problems, such as the riding up of the dressing over
      the jawline or retraction of the dressing off the lips or off the eyelids, there
      were no adverse sequelae. The wound healed rapidly and allowed the rapid
      progression to the application of a moisturizer-sunscreen or a skin-bleaching
      cream. Other than these technical problems there were no complications. No wound
      infections were noted. CONCLUSION: The use of silicone sheeting following skin
      resurfacing facilitated a rapid reepithelialization of treated areas. There was a
      remarkable reduction in erythema and edema accompanying the use of the dressing.
      The program made it possible for patients to return to work in 12-15 days.

PMID- 9598014
TI  - A double-blind randomized clinical trial on the effectiveness of a daily glycolic
      acid 5% formulation in the treatment of photoaging.
AB  - BACKGROUND: Low-strength daily formulations of glycolic acid are widely promoted
      for the treatment of photoaging. However, there are few clinical studies that
      objectively confirm the benefits of such formulations. OBJECTIVE: The purpose of
      this study was to determine the effectiveness of a 5% unneutralized formulation
      of glycolic acid in the treatment of facial and neck photoaging. METHODS: Seventy
      five volunteers were recruited to take part in this double-blind randomized
      placebo-controlled clinical study. Participants applied either the 5% glycolic
      acid cream or the placebo cream to the face and neck for a period of 3 months.
      Pre- and posttreatment clinical assessments of photoaging effects were made by
      the same physician and were analyzed for statistical significance. RESULTS:
      Overall there were trends towards greater improvement or less worsening in the
      glycolic acid group for all clinical assessments for photoaging. There was
      statistically significant improvement favoring the active-cream in general skin
      texture and discoloration. There was a trend favoring glycolic acid in reduction
      of wrinkles, but this did not achieve statistical significance. CONCLUSION:
      Unneutralized 5% glycolic acid topical cream when used on a regular daily basis
      can improve some photoaging effects.

PMID- 9598015
TI  - Rhomboid minigrafts in hair restoration surgery.
AB  - BACKGROUND: The transplantation of large numbers of three- to five-hair
      minigrafts has superseded the use of traditional punch grafts in hair restoration
      surgery. The minigrafts are usually designed and cut in a square or rectangular
      shape for implantation into the recipient slits. Transplanting a large number of
      these grafts into the recipient slits can lead to a high frequency of
      complications, especially in cases in which there is a need for dense packing of
      grafts. The complications include excess graft compression resulting in extrusion
      or retraction into the slit. This in turn can lead to piggybacking or insertion
      of two grafts per slit with the resultant effect of cyst formation,
      cobblestoning, and hypertrophic scar formation. OBJECTIVE: To develop an optimal
      shape of minigrafts to match the recipient slits. METHODS: The authors have
      calculated the optimum geometric configuration for a minigraft in a linear slit
      and have developed the correct cutting instrument and preparation technique for
      its production. This rhomboid minigraft design maximizes the graft stability in
      the slit and therefore its survival, and also minimizes the risk of
      complications. RESULTS: The described technique shows that the transplanted
      rhomboid minigrafts remain well anchored in the recipient slits and results in an
      excellent clinical outcome. CONCLUSION: The rhomboid minigrafting technique (1.5
      x 1.5 mm in size) seems to accommodate the grafts better into the recipient slits
      than the standard shape rectangular minigrafts. It thereby better facilitates the
      insertion of the grafts in the slits and reduces the frequency of graft extrusion
      as well as graft compression.

PMID- 9598016
TI  - Scalp metastases mimicking alopecia areata. First case report of placental site
      trophoblastic tumor presenting as cutaneous metastasis.
AB  - BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare neoplasm of
      intermediate trophoblastic cells of the placenta. There is a wide range of
      biologic behavior, with metastases occurring in about 15% of cases. Cases with
      metastases have all presented with abnormal vaginal bleeding or gynecological
      symptoms. METHODS: We describe a 31-year-old G3P3003 woman who presented with
      several alopecic patches resembling alopecia areata, which on biopsy proved to be
      metastatic, previously unsuspected, PSTT. CONCLUSIONS: This represents the first
      case in which PSTT presented initially with metastases, and specifically, with
      cutaneous metastases. A new primary tumor source of alopecia neoplastica is
      presented. The role of mitotic counts in predicting prognosis in PSTT is
      supported. Alopecia areata was mimicked very closely. Dermatologists should be
      alert to any features atypical of alopecia areata, including erythema,
      induration, or palpability, and maintain a low threshold for biopsy in atypical
      cases.

PMID- 9598017
TI  - Deep penetrating dermatofibroma.
AB  - BACKGROUND: Deep penetrating dermatofibroma is an unusual and histologically
      distinctive form of dermatofibroma that usually occurs on the lower extremities
      of adults. OBJECTIVE: The dermatologic surgeon and pathologist should be aware of
      this entity to prevent excessive treatment of a benign condition. METHODS: We are
      reporting a case of deep penetrating dermatofibroma with the results of
      histologic examination and immunohistochemical studies. RESULTS: The neoplasm
      consisted of a fibrohistiocytic tumor penetrating into the subcutis accompanied
      by scalloped extensions along the septae. Immunohistochemical stains were
      positive for Factor XIIIa and negative for CD34. CONCLUSION: Recognition of the
      histologic pattern is important in distinguishing deep penetrating dermatofibroma
      from dermatofibrosarcoma protuberans.

PMID- 9598018
TI  - Laser skin resurfacing. What credentials are necessary?

PMID- 9598019
TI  - Laser resurfacing and rhytidectomy.

PMID- 9598020
TI  - The resurrection of submental rhytidectomy.

PMID- 9598021
TI  - Gout: new questions for an ancient disease.

PMID- 9598022
TI  - Efficacy of allopurinol in ameliorating the progressive renal disease in familial
      juvenile hyperuricaemic nephropathy (FJHN). A six-year update.

PMID- 9598023
TI  - Optimal range of serum urate concentrations to minimize risk of gouty attacks
      during anti-hyperuricemic treatment.
AB  - To find an optimal range of urate concentrations wherein the risk of attacks
      during the initial 6 months of treatment is minimized, data from 350 gouty
      patients treated with anti-hyperuricemic drugs were retrospectively analyzed. We
      determined the optimal range of urate concentrations to be 4.6-6.6 mg/dl. If
      urate concentrations were within this range, the risk ratio of an attack as
      opposed to outside of the range was 0.705 (95% confidence interval, 0.629-0.791).
      The increase (or decrease) in urate concentration in one month associated with
      minimal risk of gouty attacks was also determined. The lowest risk ratio of
      attack (0.451) occurred at a range of -0.1 to 0.6 mg/dl/month increase in urate
      concentrations (95% confidence interval, 0.310-0.655). In conclusion, we propose
      that urate concentrations during the initial 6 months of anti-hyperuricemic
      therapy should be maintained within a range of 4.6-6.6 mg/dl, and reduction in
      the urate concentrations during treatment should be as slow as possible.

PMID- 9598024
TI  - How should we treat tophaceous gout in patients with allopurinol
      hypersensitivity?
AB  - We studied purine metabolism in gouty patients from three categories: primary
      gout, familial juvenile hyperuricaemic nephropathy (FJHN) and partial HPRT
      deficiency.

PMID- 9598025
TI  - The spectrum of HGPRT deficiency. Clinical experience based on 20 patients from
      16 Spanish families.

PMID- 9598026
TI  - Plasma uridine as well as uric acid is elevated following fructose loading.

PMID- 9598027
TI  - Inverse relationship between serum triglyceride levels and fractional urate
      excretion.

PMID- 9598028
TI  - Microanalysis of pathological crystals and urinary calculi.

PMID- 9598029
TI  - Zonal distribution of allopurinol-oxidizing enzymes in rat liver.
AB  - We describe an enzymatic histochemical localization of two allopurinol-oxidizing
      enzymes, xanthine oxidase and aldehyde oxidase in rat hepatic tissues. This
      method is based on the tetrazolium salt procedures by use of a tissue protectant,
      polyvinyl alcohol, with tetra-nitro BT as the final electron acceptor. The
      present study demonstrated that both oxidases are present in the cytoplasm of
      hepatic cells. However, the distribution of the enzymes was uneven, being seen
      mainly in the pericentral rather than the periportal area. When allopurinol was
      used as a substrate, the specific staining by xanthine oxidase was more prominent
      than that of aldehyde oxidase. The results suggested that xanthine oxidase is
      more effective in oxidizing allopurinol than aldehyde oxidase.

PMID- 9598030
TI  - Severe debilitating polyarticular gout and terminal renal failure in an
      allopurinol 'non-responder'.

PMID- 9598031
TI  - Decreased serum concentrations of 1,25(OH)2-vitamin D3 in patients with gout.
AB  - We measured the serum concentrations of 1,25(OH)2-vitamin D3, 25(OH)-vitamin D3,
      parathyroid hormone (PTH) in 82 male patients with primary gout whose serum uric
      acid was significantly higher than that of 41 normal control male subjects (8.8
      +/- 0.2 vs 5.6 +/- 0.2 mg/dL, p < 0.001). The serum 1,25(OH)2-vitamin D3
      concentration was significantly lower in the patients with gout compared with the
      control subjects (39.6 +/- 1.4 vs 44.8 +/- 1.7 pg/mL, p < 0.05), while no
      differences were observed between the two groups in either the serum
      concentration of 25(OH)-vitamin D3 or PTH. The administration of uric acid
      lowering agent to the patients for 1 year caused a significant increase in their
      serum 1,25(OH)2-vitamin D3 concentration which was associated with a significant
      decrease in their serum uric acid concentration. In contrast, the serum
      concentrations of 25(OH)-vitamin D3 and PTH were not affected by these drugs.
      These results suggest that uric acid per se may directly decrease the serum
      concentration of 1,25(OH)2-vitamin D3 in patients with gout by inhibiting 1
      hydroxylase activity.

PMID- 9598032
TI  - Lipoproteins in patients with isolated hyperuricemia.
AB  - BACKGROUND: There have been described abnormalities in the lipoprotein profile of
      hyperuricemic patients, it has not been clarified wether these abnormalities are
      due to the hyperuricemia or to the dyslipema often associated to these patients.
      Our aim is to study the apolipoprotein profile in hyperuricemic patients without
      dyslipemia compared to a control population. PATIENTS AND METHODS: 30
      hyperuricemic patients and 26 healthy controls. Measurements were of blood uric
      acid, total cholesterol, total triglycerides, creatinine, HDL-C, and VLDL
      cholesterol, triglyceride, Apo B, Apo CII and Apo CIII (1 and 2). Uric acid
      clearance and fractionated excretion were measured in 24 h. urine samples.
      RESULTS: No significant differences were found between hyperuricemic and control
      patients in cholesterol, triglycerides and apo B in VLDL, or LDL and HDL
      cholesterol. The levels of apo B, Apo AI levels and apo CIII/apo CII were similar
      in the hyperuricaemic and controls. CONCLUSIONS: There are two types of
      hyperuricaemic patients, one group associated to hyperlipideamia and would be
      included in the X Syndrome. The other group not associated to other metabolic
      abnormalities. Is important to distinguish between these two groups to define the
      prognosis of a given patient because the greater cardiovascular risk linked
      hyperuricaemic patients could be related to the association to others
      cardiovascular risks factors.

PMID- 9598033
TI  - Atherogenic risk factors in patients with gout.

PMID- 9598034
TI  - Cardiovascular actions of adenosine. Granulocyte and blood platelet adhesion in
      the reperfused myocardium.

PMID- 9598035
TI  - Mast cell adenosine receptor characteristics and signaling.

PMID- 9598036
TI  - Purine and pyrimidine nucleoside content of the neuronal extracellular space in
      rat. An in vivo microdialysis study.

PMID- 9598037
TI  - Effect of FMLP stimulation on [3H]-NECA binding to adenosine receptors in
      neutrophils membranes.

PMID- 9598038
TI  - Effects of nucleoside transport inhibitors and adenine/ribose on ATP
      concentration and adenosine production in cardiac myocytes.

PMID- 9598039
TI  - Purification of a protein involved in ADP formation.

PMID- 9598040
TI  - ADP formation in rat liver.

PMID- 9598041
TI  - A1 adenosine receptors in human neutrophils. Electron microscope localization.

PMID- 9598042
TI  - Purification and some molecular properties of pigeon heart AMP-selective 5'
      nucleotidase.

PMID- 9598043
TI  - Succinylpurines do not modify glutamate or adenosine effects in the CNS.

PMID- 9598044
TI  - Clinical and biochemical aspects of dihydropyrimidinase deficiency.

PMID- 9598045
TI  - The genetic basis of myoadenylate deaminase deficiency is heterogeneous.

PMID- 9598046
TI  - The origin of APRT*J. The most common disease-related mutation of APRT gene among
      Japanese goes back to a prehistoric era.

PMID- 9598047
TI  - HGPRT and APRT activities in hemolysates during the first year of life.

PMID- 9598049
TI  - HPRT-mutations in Italian Lesch-Nyhan patients.

PMID- 9598048
TI  - Delayed hypersensitivity to 5-fluorouracil associated with reduced
      dihydropyrimidine dehydrogenase (DPD) activity.

PMID- 9598050
TI  - Erythrocyte CDP-choline accumulation in haemolytic anaemia and renal failure
      (RF).

PMID- 9598051
TI  - Erythrocyte UMP synthetase activity. An HPLC-linked non-radiochemical assay in
      normal subjects and in one case of oroticaciduria.

PMID- 9598052
TI  - Nonrandom selection of hair follicles in HPRT heterozygosity.

PMID- 9598053
TI  - Optimised micellar electrokinetic capillary chromatography of UV-absorbing
      compounds in urine. Its application to studies on purine metabolism.

PMID- 9598054
TI  - Effect of D-ribose administration to a patient with inherited deficit of
      adenylosuccinase.

PMID- 9598055
TI  - Enzyme activities leading to NAD synthesis in the erythrocytes of HPRT deficient
      subjects.

PMID- 9598056
TI  - Succinylpurines induce neuronal damage in the rat brain.

PMID- 9598057
TI  - Urinary screening for pyrimidine metabolism disorders. Reference ranges for
      dihydrouracil, uracil, and dihydrouracil/uracil ratio.

PMID- 9598058
TI  - Carrier state in HGPRT deficiency. A study in 14 Spanish families.

PMID- 9598059
TI  - Genetic diagnosis of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
      carrier status by restriction analysis and directed mutagenesis.

PMID- 9598060
TI  - Muscle purine nucleotide cycle enzymes in exercise intolerance.

PMID- 9598061
TI  - Prenatal diagnosis of HPRT mutant genes in Lesch-Nyhan syndrome.

PMID- 9598062
TI  - Regulation of human PRS isoform expression.

PMID- 9598063
TI  - Structure and functional relationships in human pur H.
AB  - 1. The human pur H (ATIC) gene encoding a bifunctional protein, hPurH, which
      carries the penultimate and final enzymatic activities of the purine nucleotide
      synthesis pathway, AICARFT & IMPCH, has been cloned and sequenced. The gene
      product, hPurH has been overexpressed in E. coli, purified to homogeneity and
      crystallized. 2. The human pur H gene lies on chromosome 2, between band q34 and
      q35. There is at least one intron of 278 bp near the 5' end. 3. Truncation mutant
      studies demonstrate two non-overlapping functional domains in the protein
      arranged as indicated in Figure 5. The existence of a linker or interaction
      region between the catalytic domains remains to be established. 4. Cleland-type
      kinetic inhibition experiments indicate that the AICARFT reaction is of the
      ordered, sequential type with the reduced folate cofactor binding first. 5. The
      reaction has a broad pH optimum in the alkaline range, with a maximum at about pH
      8.2. 6. Preliminary transient phase kinetic studies show the presence of a
      "burst" indicating that a late step in the reaction sequence is rate limiting. 7.
      A PurH crystal structure is that of a dimer, with a putative single binding site
      for the reduced folate cofactor formed using elements from each of the monomer
      subunits. Probable binding sites for AICAR and FAICAR can be identified on each
      monomer. 8. Equilibrium sedimentation studies show hPurH apoprotein to be a
      monomer:dimer equilibrium mixture with a kD of 0.55 uM. 9. The crystal structure
      has permitted identification of a number of candidate amino acid residues likely
      to be involved in catalysis and/or substrate binding. Among these, we have thus
      far completed studies on two, Lysine 265 and Histidine 266. These appear to be
      critically involved in the AICARFT reaction, although whether their role(s) are
      in catalysis or binding remains to be determined.

PMID- 9598064
TI  - Localization of carbamoyl-phosphate synthetase II (CPS II) and aspartate
      carbamoyltransferase (ACT) genes in Trypanosoma cruzi chromosomal DNA.

PMID- 9598065
TI  - Expression and characterization of recombinant bovine cytosolic 5'-nucleotidase
      IMP-GMP specific.

PMID- 9598066
TI  - Molecular characterization of a carbamoyl-phosphate synthetase II (CPS II) gene
      from Leishmania mexicana.

PMID- 9598067
TI  - Substrate channelling by human IMP synthase.

PMID- 9598068
TI  - Inhibition of adenylosuccinate lyase by 2',3'-acyclic substrate analogs.

PMID- 9598069
TI  - Regulation of deoxycytidine kinase by deoxycytidine and deoxycytidine 5'
      triphosphate in whole leukemia and tumor cells.

PMID- 9598070
TI  - Kinetic properties of CTP synthetase from HL-60 cells.

PMID- 9598071
TI  - Cellulomonas sp. purine nucleoside phosphorylase (PNP). Comparison with human and
      E. coli enzymes.

PMID- 9598072
TI  - Subdomain structure of carbamyl phosphate synthetase. Modular construction of the
      enzyme.

PMID- 9598073
TI  - The effects of nucleotide pool on purine production in the postischemic heart.

PMID- 9598074
TI  - Muscle energy metabolism in human adenylosuccinase deficiency. An in vivo 31P-NMR
      spectroscopy study.

PMID- 9598075
TI  - Cardioprotection by ischemic preconditioning. Role of adenosine and glycogen.

PMID- 9598076
TI  - High-energy phosphate changes in the normal and hypertrophied heart during
      cardioplegic arrest and ischemia.

PMID- 9598077
TI  - Role of glutamate-67 in the catalytic mechanism of human cytidine deaminase.

PMID- 9598078
TI  - Heterozygosity for a point mutation in an invariant splice donor site of
      dihydropyrimidine dehydrogenase and severe 5-fluorouracil related toxicity.

PMID- 9598079
TI  - Site directed mutagenesis of the Saccharomyces cerevisiae APT1 gene. A functional
      and enzymatic analysis.

PMID- 9598080
TI  - Studies on cysteine residues involved in the active site of human cytidine
      deaminase.

PMID- 9598081
TI  - Relationship of the two APRT gene products from Saccharomyces cerevisiae.

PMID- 9598083
TI  - A first evidence of an asymptomatic germline missense base substitution in the
      hypoxanthine phosphoribosyltransferase (HPRT) gene in humans.

PMID- 9598082
TI  - Structural and functional analysis of the human TPMT gene promoter.

PMID- 9598084
TI  - Genetic basis of adenylosuccinase deficiency in an Italian patient.

PMID- 9598085
TI  - Mutations in xanthine dehydrogenase gene in subjects with hereditary xanthinuria.

PMID- 9598086
TI  - Role of cysteine and lysine residues in human hypoxanthine-guanine
      phosphoribosyltransferase.

PMID- 9598087
TI  - Molecular analysis of mouse Ampd3 gene encoding heart-type isoform of AMP
      deaminase.

PMID- 9598088
TI  - Dihydropyrimidine dehydrogenase deficiency. Identification of two novel mutations
      and expression of missense mutations in E. coli.

PMID- 9598089
TI  - Gene mutations responsible for human erythrocyte AMP deaminase deficiency in
      Poles.

PMID- 9598090
TI  - Response of purine metabolism to hypoxia and ischemia.

PMID- 9598091
TI  - Endothelial purine metabolism and reperfusion injury.

PMID- 9598092
TI  - Adenosine-induced preconditioning of rat neuronal cultures against ischemia
      reperfusion injury.

PMID- 9598093
TI  - Myocardial ischemic injury during cardio-pulmonary by-pass. Evaluation of purine
      compounds by capillary electrophoresis.

PMID- 9598095
TI  - Differences in nucleotide metabolism and mechanical recovery after cardioplegic
      arrest of the heart at different age.

PMID- 9598094
TI  - Nucleotide metabolism in the heart subjected to heat stress.

PMID- 9598096
TI  - Different mechanism of myocardial nucleotide breakdown during normothermic and
      hypothermic ischemia.

PMID- 9598097
TI  - Effects of adenine/ribose supply on adenosine production and ATP concentration in
      adenosine kinase inhibited cardiac cells.

PMID- 9598098
TI  - A nucleotide and nucleosides mixture solution improves recovery of energy
      metabolism after hepatic ischemia in rats.

PMID- 9598099
TI  - Can adenosine deaminase inhibitors be cytoprotective agents?

PMID- 9598101
TI  - Role of adenosine deaminase and dATP levels in thymocyte apoptosis.

PMID- 9598100
TI  - Role of purine metabolism in regulation of signal transduction in human carcinoma
      cells.

PMID- 9598102
TI  - Structure and function of P2Y2 nucleotide receptors in cystic fibrosis (CF)
      epithelium.

PMID- 9598104
TI  - Low GTP induces PKC-beta-dependent myeloid cell differentiation.

PMID- 9598103
TI  - Deoxycytidine kinase can be also potentiated by the G-protein activator NaF in
      cells.
AB  - Recently, it has been shown, that 2-Chloro-deoxyadenosine (1), a series of
      analogues, and other DNA synthesis inhibitors, increased the deoxycytidine kinase
      (dCK) enzyme activity in different cells, without influencing thymidine kinase
      isoenzymes (TK1, TK2), dCMP-deaminase and thymidylate synthase (TS) activities
      (2,3). The dCK activity was 2-4 times higher in analogue treated cells, than in
      controls, which can not be explained by metabolic pool imbalance induced by the
      drugs. New mRNA and protein synthesis of dCK could not be detected, thus post
      translational modification has been suggested for potentiation the activity of
      the dCK (1). Because secondary modifications of enzymes usually involve the
      signalling processes in cells, the universal G-protein activator fluorine ions
      were tested. dCK activity of human lymph node lymphocytes were increased 2-times,
      if cells were incubated in the presence of NaF for 1-2 hrs in cultures, while TK
      activity was not changed. The formation of dUTP from dCyd, was also enhanced by
      NaF, in parallel of dCK potentiation.

PMID- 9598105
TI  - Exogenous S-adenosyl-methionine methylates phospholipids located on the outer
      cell surface of isolated rat hepatocytes.

PMID- 9598106
TI  - IMP-dehydrogenase (IMPDH), hypoxanthine-guanine phosphoribosyltransferase
      (HGPRT), and phosphodiesterases (PDEs) expression during mycophenolic acid (MPA)
      induced differentiation in human neuroblastoma cell lines.

PMID- 9598107
TI  - Differentiating and biochemical effects of a reduction of intracellular GTP
      levels induced by mycophenolic acid (MPA) in human neuroblastoma (NB) cell lines.

PMID- 9598108
TI  - New models for the study of adenosine deaminase deficiency.

PMID- 9598110
TI  - Thymidine kinase expression. A marker for malignant cells.
AB  - The expression of thymidine kinase--an enzyme of the DNA precursor pathway--is
      strictly regulated during the normal cellular cycle, but is much higher and
      permanently expressed in malignant growing cells. Using a new cytofluorometric
      assay for thymidine kinase in single cells, we were able to discriminate between
      normal growing cells and virally transformed cells or lines derived from tumours.
      In material (blood and bone marrow) taken from leukaemia patients, we identified
      the leukaemic cells in a surplus of normal leucocytes. From cell cultures
      representing a tumour progression model, only the later, and malignant, stages
      showed enhanced fluorescence, whereas benign tumour cells looked normal.

PMID- 9598109
TI  - Insights into adenosine deaminase deficiency provided by murine fetal thymic
      organ culture with 2'-deoxycoformycin.

PMID- 9598111
TI  - Neuroblastoma cell apoptosis induced by mycophenolic acid.

PMID- 9598112
TI  - The single deoxynucleoside kinase in Drosophila melanogaster, Dm-dNK, is
      multifunctional and differs from the mammalian deoxynucleoside kinases.

PMID- 9598113
TI  - Effect of deoxynucleosides on the repair of UV induced DNA breaks.

PMID- 9598114
TI  - A new model organism for studying the catabolism of pyrimidines and purines.

PMID- 9598115
TI  - CAD overexpression in mammalian cells.

PMID- 9598117
TI  - Identification of multiple forms of the cytosolic 5'
      nucleotidase/phosphotransferase in rat tissues.

PMID- 9598116
TI  - Azathioprine treatment and thiopurine metabolism in rheumatic diseases.
      Introduction and first results of investigation.

PMID- 9598118
TI  - Regulation of deoxynucleotide pools by substrate cycles.

PMID- 9598120
TI  - Purine nucleoside phosphorylase deficient mice exhibit both an age dependent
      attrition of thymocytes and impaired thymocyte differentiation.

PMID- 9598119
TI  - Dihydroorotate dehydrogenase. Profile of a novel target for antiproliferative and
      immunosuppressive drugs.

PMID- 9598121
TI  - Activation of deoxycytidine kinase during inhibition of DNA synthesis in human
      lymphocytes.
AB  - Deoxycytidine kinase was shown to be activated during 2-chlorodeoxyadenosine
      (CdA) treatment of human lymphocytes, under the conditions when the DNA synthesis
      is inhibited. As the increase of dCK activity was shown in crude protein
      extracts, without an increase in the amount of dCK protein, shown by
      immunostaining after SDS-PAGE, a secondary modification of the protein structure
      was considered. NaF treatment of cells in the concentration range of 5-20 mM gave
      a similar activation of dCK, suggesting a possible role of phosphatases and/or a
      possibility of a G-protein related phenomenon. Using the same conditions, no
      effect of CdA or NaF was found on the thymidine kinase activity of cell extracts.
      Alternatively, activation of catabolic pathways could be considered, however, the
      increase in dCK activity was not influenced either by the removal of 5'
      nucleotidases, or by the inhibition of deaminases.

PMID- 9598122
TI  - Similar changes were induced by Cladribine and by gemcitabine, in the
      deoxypyrimidine salvage, during short-term treatments.
AB  - Short term treatments (1-2 hrs) of human tonsillar lymphocytes by Cladribine (2
      Chloro-deoxyadenosine, CdA) have suggested a new target for CdA, the inhibition
      of dCMP deaminase (Sasvari et al. 1994; BBRC 203, 1378). Further investigations
      have shown, that the dCMP-deaminase activity could be inhibited by 2-Cl-dAMP in
      cell free extracts of lymphocytes. The pool size of dUMP (measured by an antibody
      against dUMP) was also decreased in WiDr colon cancer cells by CdA. The new
      antimetabolite against solid tumours, Gemcitabine (2',2'-difluoro-deoxycytidine,
      dFdC), had similar effects on the salvage of thymidine (dThd) and deoxycytidine
      (dCyd) as CdA. The Ki values for 3H-dThd and 3H-dCyd incorporation into DNA were
      0.16 uM and 1.0 uM dFdC, respectively. The labeling of the TTP pool increased 6-7
      times, while of dCTP pool only 1.5-1.7 times, suggesting a decrease of the size
      of corresponding pools. Similarly to CdA, the labeling as well as the
      concentration of dUMP was also decreased by dFdC. Both analogues are able to
      increase the deoxycytidine kinase activity, necessary for their phosphorylation
      and therapeutic action in cells. The target(s) for the two different drugs seems
      to be common.

PMID- 9598123
TI  - Effect of Cladribine, fludarabine, and 5-aza-deoxycytidine on S
      adenosylmethionine (SAM) and nucleotides pools in stimulated human lymphocytes.

PMID- 9598124
TI  - Inhibition of inosine monophosphate dehydrogenase activity by the plasma of heart
      transplant recipients receiving mycophenolate mofetil.

PMID- 9598125
TI  - Changes of polymorphonuclear leukocyte (PMN) functions under dietary nucleic acid
      deficiency and effects of administration of nucleotide and nucleosides mixture
      solution in mice.

PMID- 9598126
TI  - Differentiation and reduction of intracellular GTP levels in HL-60 and U937 cells
      upon treatment with IMP dehydrogenase inhibitors.

PMID- 9598128
TI  - Biochemical basis for the impaired immune response in chronic renal failure?

PMID- 9598127
TI  - Isoenzymes of 5'-nucleotidase in human lymphocytes.

PMID- 9598129
TI  - Mycophenolic acid influences the expression of ICAM-1 on human endothelial cells.

PMID- 9598130
TI  - Reaction of 2',3'-dideoxynucleotides triphosphates with recombinant human
      nucleoside diphosphate kinase.

PMID- 9598132
TI  - Mechanisms of synergism between gemcitabine and cisplatin.

PMID- 9598131
TI  - Antitumor activity of yunnanmycin. A novel pyrimidine nucleoside antibiotic.

PMID- 9598133
TI  - Cross-resistance of the gemcitabine resistant human ovarian cancer cell line
      AG6000 to standard and investigational drugs.

PMID- 9598134
TI  - Increased sensitivity to gemcitabine of P-gP and MRP overexpressing human non
      small cell lung cancer cell lines.

PMID- 9598135
TI  - Does 2-chlorodeoxyadenosine contribute to alteration of DNA methyltransferase
      activity?

PMID- 9598136
TI  - Iron binding capacity of didox (3,4 dihydroxybenzohydroxamic acid) and amidox
      (3,4 dihydroxybenzamidoxime) two inhibitors of the enzyme ribonucleotide
      reductase.
AB  - Ribonucleotide reductase is the rate limiting enzyme of deoxynucleoside
      triphosphate synthesis and is considered to be an excellent target of cancer
      chemotherapy. Didox and amidox are newly synthesized compounds, which inhibit
      this enzyme and have in vitro and in vivo antitumor activity. We have now
      investigated the capability of didox and amidox to interfere with the iron
      metabolism. We show by photometric and polarographic methods, that didox and
      amidox are capable of forming an iron complex. However, their cytotoxic action
      cannot be circumvented by addition of Fe-ammoniumcitrate, indicating the iron
      complexing capacity not to be responsible for the mechanism of action of these
      compounds. When L1210 leukemia cells were incubated with the didox-iron or amidox
      iron complex itself, only slight changes of the 50% growth inhibitory capacity of
      the complex in comparison with didox or amidox alone could be shown. We conclude,
      that didox and amidox are capable of forming an iron complex, but in contrast to
      other agents, the anticancer activity cannot be contributed to this effect alone.
      Further studies will have to elucidate the molecular mechanism of action of these
      new and promising anticancer agents.

PMID- 9598137
TI  - In vitro and in vivo inhibitory activity of the differentiation-inducing agent 9
      (2-phosphonylmethoxyethyl)adenine (PMEA) against rat choriocarcinoma.
AB  - The acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) has
      previously been shown to be a strong inducer of differentiation in several tumor
      cell lines. We have now investigated the in vitro differentiation-inducing and
      the in vivo antitumor, properties of PMEA in a rat choriocarcinoma tumor cell
      model. PMEA at 2 to 50 microM induced choriocarcinoma RCHO cell differentiation
      in vitro in a concentration-dependent manner, as monitored by morphological
      changes, induction of alkaline phosphatase and production and secretion of
      progesterone. Likewise, a clear dose-response relationship was established for
      the in vivo antitumor activity of PMEA in choriocarcinoma-bearing rats. (R)-PMPA,
      a structural analogue of PMEA which is much less effective than PMEA in inducing
      differentiation in vitro did not demonstrate any in vivo antitumor activity. This
      observation points to the specificity of the differentiation-inducing potential
      of PMEA.

PMID- 9598138
TI  - Increased cell killing and mutagenecity by DNA alkylating agents in cells with
      decreased TTP pools.

PMID- 9598139
TI  - N4-hydroxy-5-halogeno-2'-deoxycytidine S and their 5'-mono-phosphates as
      inhibitors of thymidylate synthase and in vitro antileukemic agents.

PMID- 9598140
TI  - Substrate/inhibitor specificities of human deoxycytidine kinase (dCK) and
      thymidine kinases (TK1 and TK2).
AB  - Substrate/inhibitor specificities of nucleoside analogues with modified sugar
      moieties toward highly purified deoxycytidine kinase (dCK) and thymidine kinases
      (TK1 and TK2) from human leukemic spleen have been examined. Substrate activities
      of cytosine nucleosides vs dCK were as follows: 2'-fluoro-dC > 2'-O-methyl-C >
      araC > 2'-fluoro-2'-deoxy-araC > 3'-O-methyl-dC = 3'-fluoro-2',3'-ddC > cytosine
      beta-L-riboside > 2',3'-ddC > C = 1-(4-hydroxy-1,2,-butadienyl)-cytosine
      (cytalene) = 2'-azido-dC. Modified purine nucleosides were only feeble
      substrates: ara-A > 2'-fluoro-2',3'-dideoxy-araA = 2'-O-methyl-A. With TK1 and
      TK2, similar sugar-modified analogues of dU and dT were feeble substrates.
      Surprisingly alpha-dT was a relatively good substrate, as well some beta-L
      ribonucleo-sides. Several 5'-substituted analogues of dC were good non-substrate
      inhibitors of dCK and, to a lesser extent, of TK2. The overall data are relevant
      to the role of these enzymes in "activation" (by phosporylation) of nucleoside
      analogues with antiviral and antitumor activities.

PMID- 9598141
TI  - Investigation of isoenzymes of adenylosuccinase in human blood cells.

PMID- 9598142
TI  - Dihydropyrimidine dehydrogenase in livers from mouse and rat, and in human liver,
      colon tumors, and mucosa in relation to anabolism of 5-fluorouracil.

PMID- 9598143
TI  - Induction of in vivo resistance against gemcitabine (dFdC, 2',2'-difluoro
      deoxycytidine).

PMID- 9598144
TI  - Activation of deoxycytidine kinase by various nucleoside analogues.
AB  - The effect of different nucleoside analogues on deoxycytidine kinase (dCK) and
      thymidine kinase (TK) was compared in normal human lymphocytes and various
      leukemic cell lines. G-phase enriched tonsilar lymphocyte subpopulation treated
      by CdA showed more profound stimulation of dCK activity than S-phase cells. No
      substantial changes in TK activity were detected. CdA treatment increased the
      activity of dCK 4-fold in peripheral blood mononuclear cells (PBMC) and 2-fold in
      promyelocytic cell line HL60, too. However, no significant stimulation was
      detected either in CCRF-CEM or in K562 cell lines. 2-Cl-2'deoxy-2'F-adenine
      arabinoside (CAFdA), 2F-adenine arabinoside (F-araA) and cytosine arabinoside
      (AraC) had the same effect as CdA, although higher concentrations were needed for
      maximal activation. In contrast, treatment by dCyd caused slight inhibition of
      dCK. The possibility of interference of nucleoside analogues with the mechanisms
      of posttranslational modification of dCK was proposed.

PMID- 9598146
TI  - The role of thymidine kinase activity in murine colon tumours treated with 5
      fluorouracil.

PMID- 9598145
TI  - Clinical pharmacology of intermediate and low-dose cytosine arabinoside (ara-C)
      therapy in patients with hematologic malignancies.

PMID- 9598147
TI  - Role of deoxycytidine kinase (dCK), thymidine kinase 2 (TK2), and deoxycytidine
      deaminase (dCDA) in the antitumor activity of gemcitabine (dFdC).

PMID- 9598148
TI  - Differential effects of gemcitabine on nucleotide pools of 19 solid tumor cell
      lines.

PMID- 9598149
TI  - Increased activity of cytidine Triphosphate synthetase in pediatric acute
      lymphoblastic leukemia.

PMID- 9598150
TI  - Expression of human cytosolic thymidine kinase in Escherichia coli. A bacterial
      whole cell system for screening of potential antiproliferative nucleoside
      analogs.

PMID- 9598151
TI  - Structure-activity relationship in Ftorafur (Tegafur) and related 5-FU prodrugs.

PMID- 9598152
TI  - Measurement of mutation frequency at the HPRT locus in peripheral lymphocytes. Is
      this a good method to evaluate a cancer risk in pediatric patients?
AB  - Validity of measurement of somatic cell mutation frequency (Mf) at the hprt locus
      for evaluating cancer risk of the given individual was determined in pediatric
      patients. Peripheral lymphocytes (PL) from patients with various diseases,
      including acute lymphoblastic leukemia (ALL) and Hodgkin's disease (HD), DNA
      repair deficient syndromes or short stature receiving growth hormone (GH), were
      isolated through Ficoll-Hypaque sedimentation with informed consent. Mf at the
      hprt locus of PL was determined by limiting dilution assay using 6-thioguanine (6
      TG). Results were as follows. (1) ALL patients after chemotherapy had higher Mf
      than that of age-matched controls. (2) Patients with HD tended to have higher Mf
      after chemotherapy. (3) Among DNA-repair deficient syndromes, diseases which are
      susceptible to cancer (Xeroderma pigmentosum, Ataxia telangiectasia) have high
      Mf, but those without any cancer disposition (Cockayne syndrome, Rothmund-Thomson
      syndrome) have normal Mf. (4) GH-receiving patients have normal Mf, regardless of
      total doses of GH. Measurement of Mf at HPRT locus may be useful for evaluating
      cancer risk of pediatric patients.

PMID- 9598153
TI  - Thiopurine treatment in childhood leukemia. Metabolic aspects and sensitivity.

PMID- 9598154
TI  - Relationship between cladribine (CdA) plasma, intracellular CdA-5'-triphosphate
      (CdATP) concentration, deoxycytidine kinase (dCK), and chemotherapeutic activity
      in chronic lymphocytic leukemia (CLL).
AB  - Seventeen patients with CLL were treated with oral 2-chloro-2'-deoxyadenosine
      (cladribine, CdA, 10 mg/m2) on 3 consecutive days and the pharmacokinetic
      parameters of CdA in patient plasma and its intracellular nucleotides (CdAMP,
      CdATP) in circulating leukemic cells were studied after the last dose intake and
      up to 72 h thereafter. The median terminal half life (t1/2) of CdA in plasma was
      21.1 h and the area under the curve (AUC) was median 1.2 microMh. The median t1/2
      was 14.6 h for CdAMP and 9.7 h for CdATP. The AUC of CdATP in leukemic cells is
      lower than the AUC of CdAMP (median ratio 0.60). There was no correlation between
      cellular CdATP and plasma CdA concentrations or dCK activity. The clinical
      response was related to higher Cmax values for plasma CdA (p = 0.05) and higher
      products of dCK activity and CdA Cmax of plasma (p = 0.02). The activity of dCK
      alone was not related to the clinical outcome in this patient group. The results
      suggest that further steps in the mechanism of action of CdA beyond its
      bioactivation may be more important, e.g. the extent of DNA fragmentation or the
      ability of the leukemic cell to go into apoptosis, than the concentration of CdA
      nucleotides alone.

PMID- 9598155
TI  - Determinants of the therapeutic efficacy of thymidylate synthase inhibitors.

PMID- 9598156
TI  - Pyrimidine antagonists and antifolates as antimalarial drugs.

PMID- 9598157
TI  - Adenine nucleoside phosphorylases in trematode Fasciola hepatica, the mammalian
      parasite.

PMID- 9598158
TI  - Inhibition by 3'-azido-3'-deoxythymidine (AZT) of Trypanosoma cruzi growth in
      mammalian cells and a possible mechanism of action.

PMID- 9598159
TI  - Metabolism of EICAR (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide), a
      potent inhibitor of inosinate dehydrogenase.
AB  - The cytostatic agent 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide
      (EICAR) causes a rapid and marked inhibition of inosinate (IMP) dehydrogenase
      activity in intact tumor cells. [3H]EICAR is metabolised in L1210 cells to its 5'
      mono-, 5'-di- and 5'-triphosphate in a concentration-dependent manner. The
      metabolites accumulate proportionally with the initial extracellular EICAR
      concentrations (ranging from 0.25 to 200 microM). The nicotinamide adenine
      dinucleotide (NAD) analogue of EICAR, designated EAD, also accumulates within the
      cells and becomes the major metabolite after 48 hr incubation with 5 microM
      [3H]EICAR. EAD has a markedly longer intracellular half-life than EICAR 5'-mono-,
      5'-di- and 5'-triphosphate. An additional EICAR metabolite elutes on an anion
      exchange Partisphere SAX HPLC chromatogram between EICAR 5'-di- and 5'
      triphosphate. Its intracellular levels are approximately 10-fold lower than those
      of EAD and the nature of this metabolite has still to be identified. The
      differential role of EAD and EICAR 5'-monophosphate in the inhibition of IMP
      dehydrogenase is currently under investigation.

PMID- 9598160
TI  - A HPLC method for the monitoring of human red cell 6-thioguanine and methyl 6
      mercaptopurine in a single run.

PMID- 9598161
TI  - Expression and properties of recombinant P. falciparum hypoxanthine-guanine
      phosphoribosyltransferase.

PMID- 9598162
TI  - Determination of thiopurine methyltransferase activity in erythrocytes using 6
      thioguanine as the substrate.

PMID- 9598163
TI  - Antiviral acyclic nucleoside phosphonate analogues as inhibitors of purine
      nucleoside phosphorylase.

PMID- 9598164
TI  - Metabolism and anti-HIV activity of phosphoramidate derivatives of D4T-MP with
      variations in the amino acid moiety.
AB  - The metabolism of different phosphoramidate prodrugs of d4T-MP, in which the
      phosphate group is linked to a phenyl group and the alkyl ester of an amino acid
      was studied in crude CEM cell extracts. Significant (80-100%) conversion to the
      amino acyl d4T-MP metabolite was obtained with derivatives containing L-alanine
      or methyl-L-aspartic acid. A lower degree of conversion was seen with derivatives
      containing L-phenylalanine, L-methionine, methyl-L-glutamic acid or L-leucine.
      Derivatives containing D-alanine, beta-alanine, glycine, L-valine or L-lactate
      showed no conversion to the amino acyl d4T-MP metabolite. Overall, there was a
      close correlation between the anti-HIV activity of these prodrugs and their
      conversion rate to the amino acyl d4T-MP metabolite. Our data suggest that the
      enzymes involved in the formation of the amino acyl d4T-MP metabolite have a
      rather stringent specificity for L-alanine as the amino acid moiety. In addition,
      these enzymes were found to be markedly species-dependent, their activities being
      highest in mouse serum, followed by guinea pig serum, but only minimal in human
      serum. Mouse serum therefore appears to be the medium of choice to isolate and
      identify the enzymes that are involved in the metabolism of these phosphoramidate
      prodrugs.

PMID- 9598165
TI  - Determination of purine enzyme activities in human erythrocytes by capillary
      electrophoresis.

PMID- 9598166
TI  - Capillary electrophoretic analysis of hypoxanthine and xanthine for the diagnosis
      of xanthinuria.

PMID- 9598167
TI  - Ecto-nucleotidases in isolated intact rat vagi, nodose ganglia, and superior
      cervical ganglia.

PMID- 9598168
TI  - Hypoxanthine and xanthine as markers in early diagnosis of foetal diseases.

PMID- 9598169
TI  - Effects of dipyridamole and adenine/ribose on ATP concentration and adenosine
      production in cardiac myocytes.

PMID- 9598170
TI  - Evaluation of adenine concentration in plasma of patients with renal failure
      using improved ultrafiltration technique.

PMID- 9598172
TI  - De novo purine synthesis is increased in the fibroblasts of purine autism
      patients.

PMID- 9598171
TI  - A syndrome of seizures and pervasive developmental disorder associated with
      excessive cellular nucleotidase activity.

PMID- 9598173
TI  - Determination and separation of allantoin, uric acid, hypoxanthine, and xanthine
      by capillary zone electrophoresis.

PMID- 9598174
TI  - Pharmacokinetics of mycophenolate mofetil in heart transplant recipients.

PMID- 9598175
TI  - Immunohistochemical analysis of p185 and ASL activity in pre-neoplastic lesions
      and intestinal mucosa of human subjects.

PMID- 9598176
TI  - No circadian variation of dihydropyrimidine dehydrogenase, uridine phosphorylase,
      beta-alanine, and 5-fluorouracil during continuous infusion of 5-fluorouracil.

PMID- 9598177
TI  - Subcellular localization of dihydropyrimidine dehydrogenase.

PMID- 9598179
TI  - Endothelial purine content. An alternative model for testing antibiotic solutions
      for intravenous use.

PMID- 9598178
TI  - The activity of dihydropyrimidine dehydrogenase in human blood cells.

PMID- 9598180
TI  - Influence of glycopeptide antibiotics on purine metabolism of endothelial cells.
AB  - We provide evidence that the commercially available preparations of glycopeptides
      for intravenous application are well tolerated by endothelial cells when applied
      in concentrations less than 5 mg/ml. Since the antibiotics tested are
      administered at maximal concentrations of 10 mg/ml, the dose range used in our in
      vitro experiments (5 and 10 mg/ml) mimics possible clinical concentrations at the
      site of infusion. Similar concentrations may be reached by retrograde intravenous
      pressure infusion techniques (10-12). We have demonstrated that these high
      concentrations lead to considerable endothelial cell damage. These findings may
      explain the common side effect associated with intravenously applied
      glycopeptides namely pain and phlebitis at the site of infusion (2, 13). Figure 1
      shows that a detrimental effect measurable after 20 min occurs only using
      vancomycin solutions at concentrations of 10 mg/ml, whereas already a dilution to
      5 mg/ml renders the solutions more compatible to HUVEC. These data are in line
      with the observation that slow intravenous application of glycopeptides into
      large veins can largely prevent the occurrence of local phlebitis. Alternatively,
      the occurrence of phlebitis should be avoidable by diluting the manufacturers'
      preparations at least to 2-5 mg/ml and not 10 mg/ml as recommended by the
      manufacturer of vancomycin. The same aspects need to be considered for use of
      glycopeptides for retrograde high pressure infusion. The tolerance of
      intravenously applied antibiotics has previously been tested in animal models
      (4). Our model of human venous endothelial cells for testing antibiotic solutions
      for intravenous compatibility provides a valuable alternate model. In conclusion
      our data show that the commercial preparation of teicoplanin is more compatible
      for HUVEC than those of vancomycin.

PMID- 9598181
TI  - Effect of Tofu (bean curd) ingestion and on uric acid metabolism in healthy and
      gouty subjects.
AB  - The effect of Tofu (bean curd) ingestion on uric acid metabolism was examined in
      8 healthy and 10 gout subjects. Ingestion of Tofu increased plasma concentration
      of uric acid, together with increases in uric acid clearance and urinary
      excretion of uric acid. However, the increase in plasma concentration of uric
      acid was fairy small. Interestingly, no significant rise in the plasma, urinary
      and clearance of uric acid was observed in gout patients with uric acid clearance
      > 6.0 mL/min (lower normal limit). The results suggest that tofu is a preferable
      source of protein, especially in gout patients with uric acid clearance > 6.0
      mL/min.

PMID- 9598182
TI  - Purines and pyrimidines determination in urine using high-performance liquid
      chromatography.
AB  - Single purine and pyrimidine bases are involved in two fundamental metabolic
      pathways that lead to formation of the building stones of DNA and RNA. Purine and
      pyrimidine nucleotides are also critically important metabolites in many cellular
      functions. The main breakdown of purines and pyrimidines produces uric acid and B
      minoacids, respectively. Therefore, the study of purine and pyrimidine compounds
      in body fluid has high clinical relevance. We report, in this work, our
      experience in purines and pyrimidines determination in urine from children
      presenting with a clinical picture suggesting an inborn these pathways.

PMID- 9598184
TI  - Design and synthesis of the first potent, selective, and cell penetrating
      adenosine 5'-monophosphate deaminase inhibitors.
AB  - A major milestone in purine metabolism research has been achieved with the
      discovery of these potent and selective AMPDA inhibitors. These inhibitors of
      AMPDA are based on carboxypentyl substitution on N-3 of the coformycin aglycon.
      They are simpler than coformycin ribose 5'-monophosphate, more stable, selective
      against other AMP binding enzymes as well as ADA and have good cell penetration
      and good oral bioavailability. These compounds and their more potent analogs are
      the first compounds with suitable characteristics to allow a definitive analysis
      of the role of AMPDA in cellular metabolism and AMPDA as a therapeutic target.

PMID- 9598183
TI  - Design, synthesis, and structure-activity relationships of the first highly
      potent, selective, and bioavailable adenosine 5'-monophosphate deaminase
      inhibitors.
AB  - Structure-activity studies have been performed to optimize the potency of this
      novel series of AMPDA inhibitors. Conformational rigidification of the N-3
      sidechain resulted in substantial effect on the potency. Addition of the
      hydrophobic groups provided further benefit. The most potent compound identified,
      4g (Ki = 3 nM), bears little structural resemblance to AMP and exhibits a
      remarkable improvement (10(3) and 10(5)) in binding affinity relative to the
      original lead and AMP, respectively. The application of prodrug strategy achieved
      a large improvement (benzyl ester 5d) in oral bioavailability, resulting in
      compounds that should be useful in evaluating the role of AMPDA in normo- and
      pathophysiological states.

PMID- 9598185
TI  - Process-induced chemical changes in foods. An overview.
AB  - Processing of foods induces changes in their physical, chemical and sensory
      characteristics. Many researchers have shown the chemical consequences of food
      processing on acceptability and sensory attributes, nutritive value and
      wholesomeness of foods. A cursory account of these changes is provided.

PMID- 9598186
TI  - Methods to monitor process-induced changes in food proteins. An overview.
AB  - Proteins in food systems may undergo various changes in their structural
      properties as a consequence of processing. Whether these changes are beneficial
      or detrimental in terms of the nutritional, biological or functional properties
      of the processed system, it is important to apply analytical methods which can
      monitor the course of protein structural changes, in order to elucidate the
      underlying mechanism behind the results of different processes. Proteins are
      usually found in high concentrations in foods; furthermore, these proteins
      frequently may either initially be part of a solid food or may become insoluble
      due to processing. As a result, many of the traditional biochemical methods for
      analysis of protein structural properties in dilute solution cannot be applied
      directly to study food proteins. This chapter gives an overview of some potential
      methods which may be used to monitor the changes in quaternary, tertiary,
      secondary and primary structure of proteins in food systems.

PMID- 9598187
TI  - Proteolysis and gelation of fish proteins under ohmic heating.
AB  - Pacific whiting surimi gels heated slowly in a water bath exhibited poor gel
      quality, while the ohmically heated gels without holding at 55 degrees C showed
      more than a twofold increase in shear stress and shear strain over conventionally
      heated gels. Degradation of myosin and actin was minimized by ohmic heating,
      resulting in a continuous network structure. Ohmic heating with a rapid heating
      rate was an effective method for maximizing gel functionality of Pacific whiting
      surimi without enzyme inhibitors. In linear heating, slow heating rates increased
      proteolysis in Pacific whiting surimi as shown by degradation of myosin heavy
      chain and low shear stress and shear strain. Proteolysis of whiting surimi was
      decreased by the presence of beef plasma protein (BPP) to a greater extent at
      rapid heating rates (20 and 30 degrees C/min) than at slow heating rates (1 and 5
      degrees C/min). Shear stress of Alaska pollock surimi gels with or without BPP
      increased as heating rate decreased, but shear strain was unaffected. An increase
      in shear stress was accompanied by an increase of cross-linked myosin heavy
      chain.

PMID- 9598188
TI  - Effect of maturity and curing on peanut proteins. Changes in protein surface
      hydrophobicity.
AB  - A hydrophobic fluorescence probe, 1,8-anilinonaphthalene sulfonate (ANS), was
      used to study the changes in protein surface hydrophobicity (PSH) occurring
      during peanut maturation and curing. PSH increased with the degree of maturity
      and during curing (windrow drying). The increase of PSH during curing or heating
      was more pronounced in immature peanuts than their mature counterparts,
      suggesting that more hydrophobic sites are hidden in the former proteins. PSH
      decreased when proteins were chemically modified with phenylglyoxal (an arginine
      modifying agent), suggesting that arginine might play a role in hydrophobicity.
      The findings indicate that maturation and curing affect PSH, and that there is a
      relationship between PSH and peanut maturity. Possible factors contributing to
      the increase of PSH are discussed.

PMID- 9598189
TI  - High pressure processing effects on fish proteins.
AB  - Salted pastes of surimi, a myofibrillar concentrate of fish muscle, gel at
      pressures near 300 MPa. High pressure processing has been thought to induce
      denaturation and gelation of myofibrillar proteins mainly by disruption of
      protein intramolecular hydrophobic interactions which subsequently reform
      intennolecularly. We have shown that pressure-induced surimi gels evidence
      disulfide bonding as well. Endogenous transglutaminase (TGase) evidently survives
      the pressure treatment, and subsequent TGase-mediated setting of Alaska pollock
      surimi pastes at 25 degrees C results in very strong gels as compared to those
      prepared without prior pressurization. High pressure during freezing or thawing
      greatly accelerates these operations and can reduce ice crystal size and
      associated tissue damage. Yet pressure treatment can destabilize proteins which
      might lower fish quality. Infusion of certain carbohydrates into muscle prior to
      pressure-assisted freezing/thawing can achieve both baroprotection and
      cryoprotection of the muscle proteins. Pressure treatment has not proven useful
      for inactivation of proteolytic enzymes that degrade fish quality.

PMID- 9598190
TI  - Effect of high hydrostatic pressure on Pacific whiting surimi.
AB  - The effects of high hydrostatic pressure (HHP) on gel strength, microbial
      numbers, proteolytic activity, color and pH of Pacific whiting surimi gels were
      investigated. Strong gels without the use of protease inhibitors were formed with
      HHP treatments from 1-4 kBars. Gel strength was not affected by holding time.
      Total plate counts showed that destruction of vegetative cells was accomplished
      with 4 kBar. Proteolytic activity was diminished but not eliminated with pressure
      treatments. The color of the surimi gels treated were translucent while the heat
      treated gels were opaque. The pH was increased slightly with HHP treatment. HHP
      was an effective processing method for making high quality surimi gels from
      Pacific whiting.

PMID- 9598191
TI  - High pressure processing of fresh seafoods.
AB  - Crude proteolytic enzyme extracts were prepared from the muscle tissues of two
      fish species, bluefish and sheephead, and subjected to high hydrostatic pressure
      treatments (from 1,000-3,000 atm), and monitored for residual activity for
      cathepsin C, collagenase, chymotrypsin-like and trypsin-like enzymes versus
      homologous enzymes from bovine. The fish enzymes were more sensitive to
      hydrostatic pressure than the mammalian enzymes. The extent of enzyme
      inactivation achieved depended on both the amount of pressure applied, the
      duration of pressurization, and on the source material. Pressure treatment of
      fresh fish flesh formed products whose color deteriorated (cooked appearance)
      with increasing pressure as well as holding time. Application of pressure also
      improved tissue firmness or strength of fresh fish up to 2,000 atm and a holding
      time of 10 min, beyond which texture generally deteriorated. The combined use of
      pressure in combination with the broad spectrum protease inhibitor, alpha 2
      macroglobulin, enhanced the capacity of the hydrostatic pressure technology to
      achieve a more lasting inactivation of endogenous enzymes to form stable fish
      gels.

PMID- 9598192
TI  - High pressure and heat treatments effects on pectic substances in guava juice.
AB  - Effects of high pressure treatment on changes in pectic substances in guava juice
      were investigated and compared with those of heat treated samples. The viscosity
      and turbidity of guava juice pressurized at 6000 atm and 25 degrees C for 10 min
      increased slightly, whereas the viscosity of juice heated at 95 degrees C for 5
      min decreased from 362 to 285 cps while turbidity increased from 0.87 to 1.15 (OD
      600 nm). There were no apparent changes in water soluble, oxalate soluble and
      alkali soluble pectins in the pressurized juice. However, heat treated juice
      exhibited a decrease in its water and alkali soluble pectins and a slight
      increase in oxalate soluble pectin. The DEAE-cellulose profiles of pectic
      substances in guava juice were apparently unchanged after high pressure treatment
      while they were markedly changed by heat treatment, due to coagulation or
      degradation. During thermal processing, the degradation of pectin in guava juice
      caused a decrease in viscosity while the coagulation of pectin resulted in an
      increase in turbidity and cloud content. High pressure treatment showed no marked
      changes in pectic substances and cloud content in guava juice and maintained its
      natural viscous properties.

PMID- 9598193
TI  - Chemometric applications of thermally produced compounds as time-temperature
      integrators in aseptic processing of particulate foods.
AB  - The chemometric principle was used to derive a guideline for obtaining a simple
      "yes or no" answer about the sterility of food particulates heated at aseptic
      processing temperatures. A quadratic temperature pulse model was used to estimate
      bacterial destruction from the fractional yield of thermally produced chemical
      marker compounds (2,3-dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one, M-1, and 4
      hydroxy-5-methyl-3(2H)-furanone, M-2) and the rate constants and the activation
      energies of the chemical and bacterial systems. The model yielded a conservative
      estimate of lethality at the center of meat-balls heated under different time
      temperature conditions. A scheme for determining the minimum marker yield for a
      designated Fo-value is provided.

PMID- 9598194
TI  - Heating rate of egg albumin solution and its change during Ohmic heating.
AB  - Ohmic heating of egg albumin solution (10 w/v%) was examined at 50-10 kHz under a
      constant 10 V/cm. The heating rate of the solution was almost constant and
      increased slightly as the frequency increased. The gel formation was observed at
      about 75 degrees C and the heating rate increased above this temperature
      irrespective of the frequency used. The solution and gel showed almost the same
      impedance at the examined temperature (20-90 degrees C) and frequency (10 Hz-100
      kHz). When the concentration of egg albumin was reduced to 2 w/v%, no gel was
      formed and a constant heating rate at over 75 degrees C was observed. The
      breaking strength of the gels showed little difference among the gels prepared by
      boiling water or Ohmic heating. These results suggest that the liquid components
      are not compartmentalized in the gel and that the sudden increase of heating rate
      above 75 degrees C was caused by the reduction of heat transfer of the gel at its
      phase change to the gel. Ohmic heating was also applied to the fresh egg white at
      the same conditions as that of the egg albumin solution. The fresh egg white did
      not show any sudden increase of heating rate until it reached 90 degrees C.
      However, the homogenized fresh egg white and its soluble part separated
      beforehand showed a slightly reduced heating rate and a sudden increase at about
      60 degrees C. These results suggest that the gelatinous component of fresh egg
      white such as ovomucin represses the transfer of generated heat during Ohmic
      heating.

PMID- 9598195
TI  - Chemical changes during extrusion cooking. Recent advances.
AB  - Cooking extruders process a variety of foods, feeds, and industrial materials.
      Greater flexibility in product development with extruders depends upon
      understanding chemical reactions that occur within the extruder barrel and at the
      die. Starch gelatinization and protein denautration are the most important
      reactions during extrusion. Proteins, starches, and non-starch polysaccharides
      can fragment, creating reactive molecules that may form new linkages not found in
      nature. Vitamin stability varies with vitamin structure, extrusion conditions,
      and food matrix composition. Little is known about the effects of extrusion
      parameters on phytochemical bioavailability and stability. Reactive extrusion to
      create new flavor, antioxidant and color compounds will be an area of interest in
      the future.

PMID- 9598196
TI  - Sucrose loss and color formation in sugar manufacture.
AB  - The chemical reactions contributing to sucrose loss and color formation in
      evaporators in sugar manufacture (i.e., hydrolysis of sucrose and degradation of
      monosaccharides at acid pH) are reviewed. A case study of a sugar factory's
      evaporator system demonstrates that the measurement of small but real losses of
      sucrose across the process is not possible by conventional sugar factory
      analyses. Alternative, more accurate techniques (e.g., capillary gas
      chromatography or high performance ion chromatography [HPIC] with pulsed
      amperometric detection [PAD]) are considered. In the case study, glucose:sucrose
      ratios are determined by HPIC, and sucrose loss across the evaporator is
      estimated to be 1.39% of total sucrose. Loss measurements are thought to be
      underestimates; reasons for underestimation and the sources of errors are
      discussed. An approach to a more definitive loss measurement is proposed.

PMID- 9598197
TI  - Process-induced changes in edible oils.
AB  - Lipids are one of the main dietary components that serve several functions in
      foods and nutrition. They could be endogenous or deliberately included in food.
      The basic molecules of lipids undergo different chemical reactions during
      refining, processing and storage. Some of these chemical reactions enhance the
      usage and functionality of food lipids. This chapter discusses the chemical
      changes of lipids during various processing operations. Specific changes in the
      minor constituents of lipids are also included.

PMID- 9598198
TI  - Effects of processing steps on the contents of minor compounds and oxidation of
      soybean oil.
AB  - The effects of minor compounds on the oxidative stability of soybean oil were
      studied by measuring the contents of peroxides, headspace oxygen and volatile
      compounds. The effects of processing on minor component contents were also
      studied. Fatty acids, mono- and diacylglycerols, thermal or oxidized
      triacylglycerols, oxidized tocopherols and peroxides acted as prooxidant in
      soybean oil during storage at 55 degrees C. The phospholipids acted as prooxidant
      or antioxidant depending on the presence or absence of metals in the oil. The
      tocopherols acted as prooxidant or antioxidant depending on their concentration
      in the oil. The chlorophyll acted as a sensitizer to generate singlet oxygen in
      the photooxidation of soybean oils.

PMID- 9598199
TI  - Antioxidizing potentials of BHA, BHT, TBHQ, tocopherol, and oxygen absorber
      incorporated in a Ghanaian fermented fish product.
AB  - Raw whole fishes (Horse mackerel, Trachurus japonicus) were degutted and
      separately treated with antioxidants BHA, BHT, TBHQ and tocopherol before
      fermentation, by completely immersing the samples in 0.1% antioxidant solutions.
      Fish samples were then salted, fermented and dried to mark the end of processing.
      A portion of the control samples were packed in an oxygen absorber during storage
      for 2 months at room temperature to study the effect of oxygen scavenging on
      lipid oxidation. The moisture content and total lipid decreased with processing
      and storage. An inductive effect of the fish oil was observed with 2
      thiobarbituric acid values and the formation of lysophos-phatidylcholine (LPC)
      for TBHQ and BHA treated fish during the fermentation process. Free fatty acid
      formation was detected in all fish samples throughout processing and storage. For
      samples treated with tocopherol, only *-tocopherol was detected at the end of 2
      months storage. Although TBHQ showed the best antioxidative effect during
      processing, it was the fastest synthetic antioxidant to be depleted. However,
      relatively high levels of BHA were present in the sample after 2 months storage.
      Red color patches, suspected to be antioxidant degradative products, were
      observed around the operculum of TBHQ treated samples after processing.

PMID- 9598200
TI  - Minimizing process induced prooxidant stresses.
AB  - The adverse effects of trace metals, heat, steam and other conditions encountered
      in food processing relate to the acceleration of development of rancidity.
      Measures to retard oxidation of lipids, vitamins, pigments and proteins include
      elimination of prooxidants, removal of oxygen and use of blends of inhibitors
      formulated for specific substrates.

PMID- 9598201
TI  - Antioxidative properties of products from amino acids or peptides in the reaction
      with glucose.
AB  - The livers of rats fed with a brownish "soybean paste" (Miso) or peptides-glucose
      reaction mixture showed lower TBA and chemiluminescence values than those of the
      control. From these results, it was clear that Miso and peptide-glucose reaction
      products also exhibited antioxidative effect in vivo. In order to explain this
      mechanism, the scavenging activity against reactive oxygen species (ROS) of
      various Maillard reaction products (MRPs) were studied. It was confirmed that
      peptide-glucose reaction products. Amadori rearrangement products, melanoidins,
      modified protein and its hydrolysate, brown pigments isolated from Miso and other
      foodstuffs showed strong scavenging activity against hydroxyl radical and
      superoxide anion. Consequently, it was estimated that scavenging activity of MRPs
      against ROS played an important role in the antioxidative effect of MRPs in vivo.

PMID- 9598202
TI  - Maillard reaction and food processing. Application aspects.
AB  - The Maillard reaction occurs widely in food and biological systems. This
      contribution reviews the relation between the Maillard reaction and food
      processing, particularly its contribution to flavor formation, antioxidative
      effects, desmutagenic activity and the improvement of protein functional
      properties. Proteins modified by glucose, and melanoidins are important
      components of foodstuffs while the reactions of amino acids or peptides with
      glucose or dicarbonyl compounds produce various kinds of flavor components.
      Melanoidins and Amadori rearrangement products play an important role in
      providing antioxidative effects, both in vitro and in vivo. Melanoidins also
      exhibit desmutagenic activity against carcinogenic compounds. Protein
      polysaccharide conjugates, prepared by Maillard reaction at mild conditions,
      increase the emulsifying activity, as well as antioxidative and antimicrobial
      effects of the original proteins.

PMID- 9598203
TI  - Generation and the fate of C2, C3, and C4 reactive fragments formed in Maillard
      model systems of [13C]glucose and [13C]glycine or proline.
AB  - Model studies with pyrolysis/GC/MS using labeled [13C] glucoses with labeled
      [15N/13C]glycines and proline have indicated that the Maillard model systems
      consisting of glucose and glycine or proline generate similar C2, C3, C4
      fragments such as acetic acid, and pyruvaldehyde. Furthermore, the labeling
      studies have enabled the identification of the origin of these reactive
      intermediates and their stable end-products such as N-acetylpyrrolidine, 1-(1'
      pyrrolidinyl)-2-propanone amd 1-(1'-pyrrolidinyl)-2-butanone in proline model
      system and pyrazines and pyrazinones in glycine. In glycine model system,
      pyruvaldehyde and 2,3-butandione were found to be formed either from the
      degradation of the carbohydrate moiety (90 and 35%, respectively) or by an aldol
      type interaction of glycine with alpha-ketoaldehydes. The same intermediates in
      proline system are formed exclusively from the carbohydrate degradation pathway.

PMID- 9598204
TI  - Metal chelating and antioxidant activity of model Maillard reaction products.
AB  - Model glucose-lysine (Glu-Lys) and fructose-lysine (Fru-Lys) Maillard Reaction
      products (MRPs) were generated using 14 different reaction combinations, by
      varying four experimental parameters: time, temperature, initial water activity
      (aw), and initial pH. The synthesized MRPs were analyzed for their potential
      copper chelating, antioxidant or prooxidant, and genotoxic activities. Yield of
      MRPs varied depending on the conditions used to generate them. Amount of copper
      bound to MRPs ranged from 0.031-1.574 and 0.016-2.267 :mol copper per mg MRP for
      different Glu-Lys and Fru-Lys MRPs, respectively, in different synthesis
      experiments. The assessment of antioxidant activity by the 2-thiobarbituric acid
      (TBA) method using a lipid system devoid of copper ions showed varying
      antioxidant activity for both Glu-Lys and Fru-Lys MRPs. Using an oxygen electrode
      for the measurement of oxygen depletion in a model lipid system containing
      copper, as an endpoint measure of lipid peroxidation, 7 antioxidant, 2
      prooxidant, and 4 inactive MRPs and 5 antioxidant, 5 prooxidant, and 2 inactive
      MRPs were obtained for Glu-Lys and Fru-Lys MRP synthesis experiments,
      respectively. All derived MRPs showed DNA strand breaking activity above a
      concentration of 0.001% (w/v). The results indicate the importance of reaction
      conditions and the source of reducing sugar in the generation of MRPs with
      variable antioxidant, prooxidant, and genotoxic activities.

PMID- 9598205
TI  - Volatile components formed from reaction of sugar and beta-alanine as a model
      system of cookie processing.
AB  - Volatile components formed from the reaction of monosaccharides or disaccharides
      with beta-alanine were investigated in a dry condition as a model system of
      cookie processing. Maltol is a common compound formed in the Maillard reaction,
      but it was very difficult to detect it in previous experiments using actual
      cookie materials. In this work, we investigated the principal compounds and
      maltol formation from the reaction of monosaccharides or disaccharides with beta
      alanine at 150 degrees C for 10 min. Neither the reaction of monosaccharides nor
      the disaccharides with beta-alanine resulted in the formation of maltol. 2,3
      Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) was detected as a
      principal product from the reaction of monosaccharides with beta-alanine. 5
      Hydroxymethyl-2-furfural was also confirmed as being a major product in both
      reactions.

PMID- 9598206
TI  - Amino-reductones. Formation mechanisms and structural characteristics.
AB  - Various types of amino-reductones are known to be involved in process-induced
      chemical changes in foods. Since most amino-reductones, especially enaminol
      compounds are unstable reaction intermediates and are difficult to isolate, their
      structural characteristics are still unclear. In order to obtain more precise
      structural information about amino-reductones, the structures of the enaminol
      form of fructoseglysine (D-fructoseglycine = FG) and scorbamic acid (L-scorbamic
      acid = SCA), a relatively stable cyclic enaminol compound were examined by the
      use of a semi-empirical molecular orbital method. Optimized structures, heat of
      formations and charge distributions of various enol forms of FG were obtained.
      Heat of formations of the non-dissociated, mono-anion, and di-anion forms of FG
      were estimated to be about -302, -347 and -308 kcal/mol, respectively. Optimized
      structures of non-dissociated, anion, and dipolar ion forms of SCA were also
      obtained and their heat of formations were estimated to be about -197, -204 and 
      248 kcal/mol, respectively. The nitrogen atom of the enaminol group in the SCA
      molecule was found to be positively charged.

PMID- 9598207
TI  - Effects of gamma irradiation on the flavor composition of food commodities.
AB  - Fifteen food products including potato, sweet potato, shallot, onion, garlic,
      ginger, papaya, mango, rice, tobacco, small red bean, mungbean, soybean, wheat,
      flour and spices have been approved for irradiation by the National Health
      Administration in Taiwan. Market tests (Wu et al., 1996) provided strong proof
      that Taiwanese consumers would accept irradiated foods. However, researchers in
      the food industry are concerned about the possibility of chemical changes,
      especially in volatile composition, during irradiation processing. This study
      considers several food commodities, including garlic, ginger, shiitake, onion,
      potato, day-lily, tilapia, silver carp and shrimp. Food samples were irradiated
      with optimum doses and then studied for possible occurrence of chemical changes
      and effects on compositional characteristics of foods.

PMID- 9598208
TI  - Flavor deterioration in yogurt.
AB  - Volatile components of flavored yogurt preserved at 5 degrees C in the dark for 0
      day, 3 days and 10 days were recovered by simultaneous distillation extraction
      (SDE) and headspace (HS) procedures. Gas chromatography (GC) and GC-mass
      spectrometry (GC-MS) analyses of those samples showed remarkable changes in some
      compounds. Aldehydes which contribute to expressing citrusy notes were reduced to
      alcohols during fermentation process and storage. As a result, the strength of
      flavors which expressed well-balanced citrusy notes in yogurt were weakened, and
      fatty or oily notes mainly caused from alcohols were strengthened reversely.
      Hydrocarbons were also digested by bacteria during a fermentation process. A
      small amount of other compounds, such as esters and terpene alcohols changed.
      Fewer effects of sorption into a package material and chemical reactions, such as
      hydrolysis esters, hydration or oxidation of hydrocarbons, were observed.

PMID- 9598209
TI  - Flavor generation during extrusion cooking.
AB  - Extrusion cooking is a high temperature-short time process which is ideal for the
      production of flavor volatiles. However, due to the nature of this process there
      are many opportunities for these volatiles to be lost. This has led many
      researchers to study the formation and retention of volatiles during extrusion.
      This review will focus on-the flavor related reactions which may occur during
      extrusion and their occurrence in various flours and due to the addition of
      reactive precursors.

PMID- 9598211
TI  - Effect of processing on phenolics of wines.
AB  - Phenolics of grapes are the main compounds responsible for color, taste, mouth
      feel, oxidation and other chemical reactions in wine and juice. Phenolic levels
      in wine and juice are affected by numerous processing conditions (crushing,
      pressing, sulfite addition, skin contact, oak aging). Studies were conducted to
      better understand the effect of processing on phenolic composition of three
      varieties of grapes. Three different processing steps: immediate press, hot
      press, and hull treatment (skin contact) for 7 and 14 days were applied to three
      different grape varieties, Vitis rotundifolia cv. Noble, Vitis vinifer cv.
      Cabernet Sauvignon, and the French-American hybrid Chambourcin. Phenolic
      compounds were identified and quantified by High Performance Liquid
      Chromatography (HPLC) and bitterness/astringency were assessed using a trained
      sensory panel. V. rotundifolia wines had higher levels of epicatechin and gallic
      acid but lower caftaric acid and procyanidins compared to the other varieties and
      were more astringent and bitter. Processing treatment affected phenolics and
      color differently among the three varieties.

PMID- 9598210
TI  - Process-induced compositional changes of flaxseed.
AB  - Flaxseed has been used as an edible grain in different parts of the world since
      ancient times. However, use of flaxseed oil has been limited due to its high
      content of polyunsaturated fatty acids. Nonetheless, alpha-linolenic acid,
      dietary fiber and lignans of flaxseed have regained attention. New varieties of
      flaxseed containing low levels of alpha-linolenic acid are available for edible
      oil extraction. Use of whole flaxseed in foods provides a means to utilise all of
      its nutrients and require minimum processing steps. However, the presence of
      cyanogenic glucosides and diglucosides in the seeds is a concern as they may
      release cyanide upon hydrolysis. In addition, the polyunsaturated fatty acids may
      undergo thermal or autooxidation when exposed to air or high temperatures that
      are used in food preparation. Studies todate on oxidation products of intact
      flaxseed lipids have not shown any harmful effects when flaxseed is included, up
      to 28%, in the baked products. Furthermore, cyanide levels produced as a result
      of autolysis are below the harmful limits to humans. However, the meals left
      after oil extraction require detoxification but, by solvent extraction, to reduce
      the harmful effects of cyanide when used in animal rations. Flaxseed meal is a
      good source of proteins; these could be isolated by complexation with sodium
      hexametaphosphate without changing their nutritional value or composition. In
      addition, the effect of germination on proteins, lipids, cyanogenic glycosides,
      and other minor constituents of flaxseed is discussed.

PMID- 9598212
TI  - Photochemical reactions of flavor compounds.
AB  - Photochemical reaction is a chemical reaction which is initiated by light. In
      addition to light, photosensitizer and oxygen are the two important factors which
      contribute to the formation of photochemical products. In this contribution,
      photochemical reactions of flavor compounds are classified into four categories
      according to the factors of photosensitizer and oxygen. Photochemical reaction
      with or without sensitizer in the absence of oxygen and unsensitized
      photochemical reaction in the presence of oxygen usually involve free radical
      reactions; while in the presence of oxygen and sensitizer, the singlet oxygen can
      be generated that then reacts with flavor compounds which contain double bonds to
      give the oxygenated products.

PMID- 9598213
TI  - Prevalence and risk factors of illicit drug use by people with disabilities.
AB  - The authors examined patterns and risk factors of illicit drug use among people
      with disabilities by use of a random sample of 1,876 persons actively involved in
      vocational rehabilitation services in three Midwestern states. Compared with
      regional drug use data from the general population, respondents with disabilities
      reported higher rates of illicit drug use for nearly every drug category. Factors
      significantly associated with illicit drug use included level of disability
      acceptance, best friends' drug use, attitude of disability entitlement, self
      esteem, and risk-taking. These findings provide additional insight into illicit
      drug use among people with disabilities. The authors discuss implications from
      these findings for rehabilitation and disability policy.

PMID- 9598214
TI  - Effects of deviant child behavior on parental alcohol consumption. Stress-induced
      drinking in parents of ADHD children.
AB  - Distress and ad lib alcohol consumption after interactions with child
      confederates were investigated in parents of children with externalizing
      disorders--attention-deficit hyperactivity disorder (ADHD), conduct disorder
      (CD), or oppositional defiant disorder (ODD). Sixty subjects interacted with boys
      trained to act like either normal children or children with ADHD/CD/ODD.
      Interactions with deviant confederates resulted in feelings of inadequacy and
      produced negative affect but had no effect on alcohol consumption. Post hoc
      analyses showed that parents with a family history of alcohol problems (FH+)
      showed increased drinking after interaction with a deviant confederate, compared
      with FH+ parents who interacted with the normal confederate. FH- parents showed
      the opposite pattern of results.

PMID- 9598215
TI  - Psychosocial risk and protective factors for condom use among female injection
      drug users.
AB  - The authors examined the influences of domains of psychosocial risk and
      protective factors on male-partner condom use in a cobort of 209 female HIV
      positive (HIV+) and HIV-negative (HIV-) injection drug users (IDUs) by use of a
      cross-sectional, retrospective design. Information collected from a structured
      questionnaire included data on psychosocial risk and protective factors in the
      personality, family, and peer domains; HIV status; and condom use. Among HIV+
      IDUs, personality risk factors (e.g., unconventionality), family (e.g., low
      maternal identification), and peer factors were related to less male-partner
      condom use. Resources and condom availability were associated with greater male
      condom use with both HIV+ and HIV- IDUs. The psychosocial domains affected male
      condom use with both HIV+ and HIV- female IDU patients via two different
      mediational models. The findings suggest the need to use specific psychosocial
      interventions for risky sexual behavior among HIV+ and HIV- female IDUs.

PMID- 9598216
TI  - Posttraumatic stress disorder and cocaine dependence. Order of onset.
AB  - To investigate differences between patients whose posttraumatic stress disorder
      (PTSD) preceded their cocaine dependence and vice versa, 33 patients with
      comorbid PTSD and cocaine dependence were divided into two groups: one in which
      the traum and PTSD occurred before onset of cocaine dependence (primary PTSD) and
      one in which the PTSD occurred after cocaine dependence was established (primary
      cocaine). In the primary-PTSD group, the trauma was generally childhood abuse. In
      the primary-cocaine group, the trauma was generally associated with the
      procurement and use of cocaine. In the primary PTSD group, there were
      significantly more women, more other Axis I diagnoses, more Cluster B and C Axis
      II diagnoses, and more benzodiazepine and opiate use. In the primary-cocaine
      group, there was a trend toward more cocaine use in the previous month.
      Significant clinical differences between these two groups may warrant different
      types of treatment or differing treatment emphasis.

PMID- 9598217
TI  - Impact of social anxiety in a "therapeutic community"--oriented cocaine treatment
      clinic.
AB  - The authors assessed social-evaluative anxiety in 50 cocaine abusers attending an
      outpatient therapeutic-community (TC)-oriented clinic. This group-based modality
      presumes that the ability of clients to self-disclose is key to recovery. Fully
      half of the clients tested, some of whom had been attending treatment for a
      number of months, showed an elevation of social withdrawal and distress.
      Newcomers with higher social anxiety scores were less likely to drop out of
      treatment over the first 3 months, and self-reported level of social anxiety
      decreased over this time interval. These findings suggest that social anxiety may
      be an important consideration in treatment for cocaine abuse and that the rigors
      of a modified TC with intense focus on group involvement may reduce social
      anxiety.

PMID- 9598218
TI  - Effect of fenfluramine challenge on cocaine craving in addicted male users.
AB  - The authors studied the effects of a challenging dose of the serotonin (5-HT)
      releaser/reuptake inhibitor d,l-fenfluramine (FEN) on spontaneous cocaine craving
      in a group of cocaine-addicted users in order to evaluate the involvement of
      serotonergic pathways in the modulation of craving for cocaine. Nineteen cocaine
      dependent male inpatients received 60 mg of FEN or placebo (double-blind). Data
      were compared with those obtained in a previous study of another serotonergic
      probe, the partial postsynaptic agonist meta-chlorophenyl-piperazine (m-CPP). FEN
      significantly reduced cocaine craving and increased cortisol and prolactin when
      compared with placebo. When the responses to the two drugs were compared, there
      were no differences in the cortisol and prolactin rises, but m-CPP was a more
      potent inhibitor of cocaine craving than FEN. These data suggest that 5-HT
      releasers/reuptake inhibitors and serotonergic agents with greater postsynaptic
      activity should be further examined.

PMID- 9598219
TI  - Does ADHD affect the course of substance abuse? Findings from a sample of adults
      with and without ADHD.
AB  - The authors examined the effects of attention-deficit hyperactivity disorder
      (ADHD) and psychiatric comorbidity on recovery from psychoactive substance use
      disorder (PSUD) with 130 referred adults with ADHD and 71 non-ADHD adults, all of
      whom had a lifetime history of PSUD. Although PSUD remitted in 80% of both
      groups, the rate of remission and duration of PSUD was quite different in the
      ADHD vs. non-ADHD subjects. The duration of PSUD was 37.2 months longer in the
      ADHD than in non-ADHD subjects. The median time to PSUD remission was more than
      twice as long in ADHD than in control subjects (144 vs. 60 months, respectively).
      ADHD is associated with a longer, duration of PSUD and a significantly slower
      remission rate. If confirmed, such findings extend previous work showing that
      ADHD is a risk factor for early initiation and specific pathways of PSUD,
      providing further evidence of the relevance of this association.

PMID- 9598220
TI  - Auricular acupuncture as an adjunctive treatment for cocaine addiction. A pilot
      study.
AB  - The authors conducted a single-blind study of auricular acupuncture in 36 cocaine
      dependent inpatient veterans on a substance abuse treatment unit to determine
      whether the treatment could help reduce craving, increase treatment retention,
      and prevent relapse. Acupuncture was given on a predetermined schedule to both
      treatment and control groups, with status assessed regularly by independent,
      blinded raters. The study failed to show a significant difference between
      treatment and control groups. However, the study patients, as a whole, did remain
      in treatment longer than a retrospectively analyzed group who received no
      acupuncture.

PMID- 9598221
TI  - Laparoscopic hernia repair.

PMID- 9598222
TI  - What is the impact of guidelines for the surgical treatment of breast cancer?

PMID- 9598223
TI  - The magnitude of adhesion related problems.

PMID- 9598224
TI  - Bioabsorbable fixation devices in Orthopaedics and Traumatology.

PMID- 9598225
TI  - Laparoscopic versus open preperitoneal inguinal hernia repair: a prospective
      randomised trial.
AB  - BACKGROUND AND AIMS: Before choosing between open and laparoscopic preperitoneal
      tension-free repair, a study comparing their safety and short-term outcome was
      needed. No randomised studies comparing the two hernia repair techniques have
      hitherto been published. MATERIAL AND METHODS: A prospective randomised study was
      carried out comparing laparoscopic transabdominal preperitoneal mesh
      herniorrhaphy (n = 24) to open preperitoneal mesh herniorrhaphy (n = 25).
      RESULTS: When comparing unilateral repairs, the mean operation time was
      significantly (P < 0.01) shorter in the open group (55 min) than in the
      laparoscopic group (66 min). Pain on movement (P < 0.05) and pain on coughing (P
      < 0.01) receded more rapidly in the laparoscopic group. The median time before
      return to work or normal activity was 7 days (range 1-60) in laparoscopic and 5
      days (1-30) in open repair. There were five (21%) complications associated with
      the laparoscopic procedure, while the open procedure resulted in two (8%)
      complications. After a median follow-up of 18 months the recurrence rate in the
      laparoscopic group was 13% and in the open group 8%. CONCLUSIONS: In this study
      the open method was associated with fewer complications and recurrences than the
      laparoscopic technique. Despite the decreased postoperative discomfort after
      laparoscopic repair, there was no significant difference in median time before
      return to work or normal activity. These results together with the higher cost of
      the laparoscopic procedure suggest that the open method is more suitable at least
      for unilateral hernias.

PMID- 9598226
TI  - Breast conservation or mastectomy in breast cancer: factors affecting the choice
      of operation.
AB  - BACKGROUND AND AIMS: In the surgical treatment of breast cancer, breast
      conservation is considered preferable to mastectomy provided that certain
      prerequisites are fulfilled. This retrospective analysis reports those factors
      which affected the choice between operations. MATERIAL AND METHODS: In 1993, a
      total of 104 women were operated on for breast cancer or carcinoma in situ in the
      Department of Surgery, University Central Hospital of Turku. There was a palpable
      tumour in 75%. In 23% the disease was found at mammography screening. RESULTS AND
      CONCLUSIONS: Breast conservation was achieved in 24%. The proportion was about
      the same whether the disease was found at screening or clinically (27% and 23%).
      In the presence of a palpable tumour breast conservation tended to succeed
      slightly more often than in wire-guided operations (26% versus 19%).

PMID- 9598227
TI  - Problems in wearing external prosthesis after mastectomy and patient's desire for
      breast reconstruction.
AB  - BACKGROUND AND AIMS: To evaluate the inconvenience caused by an external
      prosthesis and the desire for breast reconstruction among Finnish breast cancer
      patients. MATERIAL AND METHODS: A questionnaire was sent to 345 mastectomized
      women 2-58 months after surgery between 1989 and 1993; 176 questionnaires were
      eliglible for review. Response rate was 63%. RESULTS: Mean age of the patients
      was 58 years, and 91% wore an external prosthesis. Of the patients under 65 years
      old, 46% wished to have reconstruction, but only one patient in the group 65
      years old or older was interested in reconstructive surgery. In this study,
      interest in reconstructive surgery did not decrease with time. Younger patients
      had more difficulties and inconvenience with the prosthesis in every-day life
      while working, enjoying leisure time pursuits and wearing clothing. CONCLUSIONS:
      Breast cancer patients under 65 years have considerable problems with external
      prosthesis in every-day life. This is the group of patients therefore, that
      should be considered when evaluating the need for breast reconstruction in the
      community. Of new breast cancer patients in Finland, 40% per cent are between 45
      and 59; about 50-70% of them will have a mastectomy. Our study suggests that
      breast reconstruction is needed for about half of these patients. Therefore, the
      annual need for breast reconstruction in Finland involves about 370 women.

PMID- 9598229
TI  - Angiogenesis is associated with mononuclear inflammatory cells in abdominal
      aortic aneurysms.
AB  - BACKGROUND AND AIMS: To evaluate the extent of neovascularisation in abdominal
      aortic aneurysms, specimens from the aneurysm walls of 17 consecutive patients
      (14 men, mean age 69 years, range 59 to 79 years) were studied and compared with
      specimens from patients with aortoiliac occlusive disease (n = 8, five men, mean
      age 53 years; range 40 to 71 years). Routine histology was performed after
      haematoxylin and eosin, Verhoeff's elastic and periodic acid-Schiff stainings.
      For immunophenotypic analysis of inflammatory cells four monoclonal mouse
      antibodies (UCHL1, L26, PG-M1 and KP1) were used. RESULTS: The histological
      sections through the walls of the AAAs showed extensive destruction of elastin
      and variable inflammation. Dense neovascularisation was seen throughout the
      aortic wall in the AAA cases compared to a mild angiogenetic response seen only
      occasionally in the AODs. CONCLUSIONS: Angiogenesis may play a significant role
      in the AAA process by recruiting and carrying a macrophage-rich infiltrate to the
      aortic wall.

PMID- 9598228
TI  - Pericardial closure with polytetrafluoroethylene surgical membrane or
      biodegradable polyglycolic acid mesh after coronary artery bypass surgery--a
      baseline report.
AB  - BACKGROUND AND AIMS: Complete and tight closure of the native pericardium may
      kink or even occlude bypass grafts after coronary artery bypass grafting (CABG)
      and therefore the feasibility of tight closure has been debated. The growing
      number of reoperations has raised the question how to reduce the risk of damage
      of the right ventricle and patent grafts. We are performing a prospective
      randomized trial aiming to evaluate the feasibility of polytetrafluoroethylene
      (PTFE) surgical membrane and biodegradable polygycolic acid (PGA) mesh as
      pericardial substitutes for closure purposes in patients undergoing primary
      isolated CABG surgery. MATERIAL AND METHODS: The series comprises 540 patients
      who underwent a primary isolated CABG procedure at the Oulu University Hospital
      from October 1989 to May 1994. RESULTS AND CONCLUSIONS: The baseline results
      suggest that the PTFE and PGA materials seem to be similar despite the subtle
      early expression of tamponade related to the PTFE membrane after postoperative
      bleeding.

PMID- 9598230
TI  - Absorbable fixation of femoral head fractures. A prospective study of six cases.
AB  - BACKGROUND AND AIMS: Fracture of the femoral head associated with a traumatic
      dislocation of the hip is a rare but severe injury. The methods of the
      recommended treatment have varied from primary closed or open reduction without
      fixation to excision of fragments or internal fixation. In our department we have
      treated other kinds of intra-articular fractures successfully with totally
      absorbable polyglycolide and poly-L-lactide implants. The aim of this study was
      to investigate the value of totally absorbable rods and screws in the fixation of
      the femoral head fractures. MATERIAL AND METHODS: Six femoral head fractures
      associated with a posterior traumatic dislocation of the hip were treated by open
      reduction and internal fixation using self-reinforced absorbable polyglycolide
      (SR-PGA) or poly-L-lactide (SR-PLLA) rods and screws. The follow-up time was 38
      months in average (range 6 weeks to 77 months). RESULTS: In three patients the
      end results were excellent and in one fair. One patient died six weeks after the
      accident from the consequences of the cerebral injury. In one 61-year-old patient
      an arthroplasty was performed one year after the primary osteosynthesis, because
      of avascular necrosis of the femoral head. CONCLUSIONS: Self-reinforced
      polyglycolide and polylactide implants can be used safely to fix femoral head
      fractures without the need of implant removal.

PMID- 9598231
TI  - Complications after treatment of proximal femoral fractures.
AB  - BACKGROUND AND AIMS: The number of fractures of the proximal femur is increasing
      faster than the number of elderly people. The aim of the study was to record all
      complications after operative treatment of proximal femoral fractures in order to
      reduce the incidence of these complications in the future. MATERIAL AND METHODS:
      The files of 334 patients with proximal femoral fractures were retrospectively
      analyzed. The number of all general and operative complications were recorded.
      RESULTS AND CONCLUSIONS: The primary mortality was 8 percent. The most common
      general complication was a thromboembolic one. Local complications were recorded
      in 66 cases. Thirty-eight percent of femoral neck fractures treated by internal
      fixation were complicated. Increased attention should be focused on the
      sufficient antithrombosis prophylaxis, which should be continued at least during
      the whole convalescence period at the hospital. It remains to be clarified, if
      improved technical skill may improve the results of femoral neck osteosynthesis,
      which in this group of patients appeared far from satisfactory. The development
      of post-operative care and selection of right patients to an appropriate
      rehabilitation program is perhaps the most important factor today, in order to
      reduce complications in general.

PMID- 9598232
TI  - Chronic compartment syndrome of the quadriceps femoris muscle in athletes.
      Diagnosis, imaging and treatment with fasciotomy.
AB  - BACKGROUND AND AIMS: Chronic quadriceps femoris muscle compartment syndrome is
      described. MATERIAL AND METHODS: Over a 13 year period nine patients were
      diagnosed, treated surgically by fasciotomy and followed up at a referral center
      specialized in sports traumatology. There were four power lifters, three body
      builders, one endurance walker and one cyclist in the series. The use of anabolic
      steroids was admitted by four of the nine patients. The patients complained of
      gradually worsening pain on the anterolateral side of the thigh during training.
      Initially the pain appeared only at the end of the training session. As the
      syndrome became more severe, the pain began earlier during exercise and gradually
      became worse preventing maximal training. Skeletal radiographs and ultrasound
      examinations were normal, except in two patients, who had a positive echography
      finding with local atrophy. MRI examination confirmed the US diagnosis. RESULTS
      AND CONCLUSIONS: As conservative treatment did not provide relief of symptoms, a
      fasciotomy anterior to the iliotibial tract was performed bilaterally to seven
      patients and unilaterally to two patients. Biopsies from the atrophied sites
      showed muscle cell necrosis. All the patients recovered well after the surgery
      and were able return to their original level of sport. The only complication of
      surgery was a postoperative hematoma in one patient, which delayed the beginning
      of the training, but did not result in any persistent complaints.

PMID- 9598234
TI  - Surgery for aneurysms and dissections of the thoracic and thoracoabdominal aorta.

PMID- 9598233
TI  - Prostate cancer and bone metastases. The effect of clodronate.

PMID- 9598235
TI  - Expansion and rupture of abdominal aortic aneurysms.

PMID- 9598236
TI  - Clinical and radiographic outcome of total hip arthroplasty--factors related to
      loosening.

PMID- 9598237
TI  - Surgical methods in treating gallbladder stones and stones in the common bile
      duct.

PMID- 9598238
TI  - Fractures of the tibial plateau.

PMID- 9598239
TI  - Hip fractures in the elderly--epidemiology, injury mechanisms, and prevention
      with an external hip protector.

PMID- 9598240
TI  - Ulcerative colitis--association with primary sclerosing cholangitis and
      colorectal neoplasia.

PMID- 9598241
TI  - Early phase of acute pancreatitis, screening, diagnosis and severity grading with
      new laboratory markers and imaging techniques.

PMID- 9598242
TI  - Lipid metabolism during postresectional adaptation of intact and autotransplanted
      porcine ileum. An experimental study of nonrejecting ileal graft adaptation and
      function.

PMID- 9598243
TI  - Late outcome of paediatric burns-scarred for life?

PMID- 9598245
TI  - Rhythm and conduction disturbances after coronary artery bypass grafting. The
      role of ischemia and myocardial protection.

PMID- 9598246
TI  - Introduction to the surgical treatment of gastric cancer: anatomical borders and
      dissection of lymph nodes.

PMID- 9598244
TI  - Surgical site infections after coronary artery bypass surgery, with special
      reference to antibiotic prophylaxis and risk factors.

PMID- 9598247
TI  - Surgical treatment of gastric cancer: anatomical borders and dissection of lymph
      nodes.

PMID- 9598248
TI  - Principles and guidelines for surgeons--management of symptomatic breast cancer.
      On behalf of the European Society of Surgical Oncology.
AB  - The European Society of Surgical Oncology is actively involved in the promotion
      of a high standard of surgical oncology throughout Europe. Such an ambition
      involves recognition of Centres of Excellence in the management of cancer
      patients throughout Europe. These centres have a multi-disciplinary system
      involved in the total care of patients with cancer and are concerned with the
      delivery of care to the highest available standards. It is accepted that not all
      patients with cancer can, nor should, necessarily be treated in such highly
      specialized centres. Yet all cancer patients should be guaranteed a high standard
      of care. High surgical standards can be ensured if surgeons treating cancer are
      trained in specialist centres and, when in independent practice, follow
      established guidelines or protocols of treatment. In common with many national
      surgical oncology societies, the European Society of Surgical Oncology is in the
      process of establishing good practice guidelines in the treatment of solid
      tumours. This document on the management of symptomatic breast cancer is the
      first of a series of guidelines to be proposed by ESSO. It draws heavily on
      excellent documents already in existence from the British Association of Surgical
      Oncology and from the Danish Breast Cancer Co-Operative Group. It is hoped that
      this document will be sufficiently clear and purposeful to be of help to the
      individual surgeon and yet sufficiently flexible to allow it to be adopted in the
      different medical systems throughout Europe.

PMID- 9598249
TI  - European guidelines for quality assurance in the surgical management of
      mammographically detected lesions. European Breast Cancer Working Group.
AB  - The European Guidelines developed for mammography screening have contributed to
      the general discussion on quality assurance and the important tasks of the health
      professionals dealing with breast cancer screening. The cooperation of each
      medical discipline is of utmost importance in order to achieve optimal results
      and eventually a mortality reduction. The following guidelines are based on the
      British NHS quality assurance guidelines for surgeons in breast cancer screening
      and modified to meet the different needs in the European Countries. The term
      "surgeon" denotes a medical doctor trained and involved in the surgical treatment
      of breast diseases. The members of the working group who participated in order to
      adapt these guidelines are listed above. We hope that this document will
      contribute towards a more comprehensive approach of breast cancer screening
      detected lesions throughout Europe.

PMID- 9598250
TI  - Somatosensory evoked potentials during spinal surgery.

PMID- 9598251
TI  - The best approach to ARDS?

PMID- 9598252
TI  - A rapid precurarization technique using rocuronium.
AB  - PURPOSE: To evaluate a rapid and time-saving precurarization technique using
      rocuronium to prevent succinylcholine-induced myalgia. METHOD: In a prospective,
      double blind randomized study, 42 ASA 1-2 patients were assigned to one of three
      pretreatment groups: 0.01 ml.kg-1 normal saline, 0.1 mg.kg-1 atracurium, and 0.1
      mg.kg-1 rocuronium. Anaesthesia commenced with 1.5 micrograms.kg-1 fentanyl and
      0.5 mg.kg-1 lidocaine at time zero. Pretreatment was administered 60 sec later,
      followed by 2.5 mg.kg-1 propofol. At 90 sec, 1.5 mg.kg-1 succinylcholine was
      injected and 30 sec later, the trachea was intubated and the ease of intubation
      was graded. The patient was observed for the presence and severity of
      fasciculations. Myalgias were recorded on postoperative days 1, 2 and 7. RESULTS:
      The incidence of fasciculations in the rocuronium group (21.4%) was lower (P <
      0.001) than atracurium (78.5%) or placebo (92.8%) groups. On postoperative day 1,
      the incidence of postoperative myalgia in the rocuronium group (14.2%) was less
      than the placebo group (78.2%; P < 0.002) and atracurium group (85.7%; P <
      0.001). The incidence of myalgia in the rocuronium group (7.1%) was lower than in
      the placebo group (78.5%; P < 0.001) but not different from the atracurium group
      (42.8%; P = 0.077) on postoperative day 2. On postoperative day 7, there was no
      difference among the three groups. Fasciculations were related to postoperative
      myalgia. There was no difference in intubating conditions among the three groups.
      CONCLUSION: Rocuronium pretreatment given just before induction of anaesthesia
      with propofol reduces fasciculations and succinylcholine-induced myalgia.

PMID- 9598253
TI  - Combined nitric oxide inhalation, prone positioning and almitrine infusion
      improve oxygenation in severe ARDS.
AB  - PURPOSE: To determine the efficacy and side effects of prone positioning (PP) and
      nitric oxide (NO) inhalation, alone, associated, or combined with i.v. almitrine
      for the treatment of hypoxaemia in severe acute respiratory distress syndrome
      (ARDS). METHODS: Over a period of 20 months, 27 consecutive critically ill
      patients with severe ARDS (Murray score > 2.5, PaO2/FiO2 < 170 after alveolar
      recruitment) were prospectively and randomly included. They inhaled NO for two
      hours at concentrations of 5 and 10 ppm for one hour each (H0-H2). One hour
      later, they were returned to the prone position for four hours (H3-H7). During
      the last two hours in this position (H5-H7), they were assigned to further
      inhalation of 10 ppm NO (Group B, n = 9) or to no further inhalation (Group A, n
      = 9). In group C (n = 9), the procedure for group B was combined with perfusion
      of 16 mg.kg-1.min-1 almitrine throughout the study. RESULTS: Compared with
      control values, two hours NO inhalation improves PaO2/FiO2 and shunt effect by
      +28% and -9%, PP by +88% and -27%, PP + almitrine by +132% and -28%, NO +
      almitrine by +153 and -28%, PP + NO by +94% and -29%, NO + PP + almitrine by +327
      and -48%. NO inhalation reduces pulmonary vascular resistance. Other haemodynamic
      parameters remain unchanged, whatever the treatment. NO inhalation improves
      PaO2/FiO2 by over 20% in 50% of the patients and PP is effective in 78% of the
      cases. CONCLUSION: Prone Position improves PaO2/FiO2 significantly more than NO
      alone but less than PP + almitrine or NO + almitrine. The best results are
      obtained with the association of NO + Prone position + Almitrine.

PMID- 9598254
TI  - Age related variability in the effects of mivacurium in paediatric surgical
      patients.
AB  - PURPOSE: This study describes the effects of 0.3 mg.kg-1 mivacurium in 180
      paediatric patients between the ages of one month and 13 yr. METHODS: Alternate
      patients at each of two geographic sites received nitrous oxide-halothane or
      nitrous oxide-opioid anaesthesia. Neuromuscular blockade was monitored by
      electromyography (Datex NMT). Blood pressure and heart rate were recorded from an
      automated oscillometer. Tracheal intubation was performed 90 sec after
      administration of mivacurium and conditions were judged by the Krieg scale.
      RESULTS: There was no difference in the time course of block between anaesthetics
      or geographic sites. The average time to 90% block and 25% recovery was 1.0 min
      and 8.0 min at one month vs 2.3 min and 9.8 min at 12.5 yr of age. Intubation
      conditions were better during opioid (excellent in 92%) than during halothane
      anaesthesia (excellent in 78%) (P = 0.03). Diaphragmatic movement was less
      frequent in younger patients (P < 0.001). Intubation conditions did not differ
      between the two geographic sites. In the first minute after mivacurium, systolic
      and diastolic blood pressures decreased (P < 0.001) to similar extents in all
      patients. A transient increase in the redness of the skin of the face, trunk,
      and/or arms was noted during both anaesthetics (28% of infants, and 61% of
      children over five yr of age). CONCLUSION: The time course of block produced by
      mivacurium is more rapid in younger paediatric patients. The time course of
      mivacurium does not have the transatlantic variation which has been observed for
      vecuronium. Physiological changes suggestive of histamine release were frequent.
      Intubation conditions were very likely to be acceptable 90 sec after 0.3 mg.kg-1
      mivacurium.

PMID- 9598255
TI  - Propofol reduces succinylcholine induced increase of masseter muscle tone.
AB  - PURPOSE: Succinylcholine is known to increase the tone of the masseter muscles.
      As excessive jaw tension may complicate rapid sequence induction, we investigated
      three induction techniques, all including the use of succinylcholine, with
      respect to masseter muscle tone, neuromuscular blockade, intubation conditions,
      and time course of intubation. METHODS: Sixty adult patients were allocated to
      one of three induction groups: Group THIO received 5 mg.kg-1 thiopentone, Group
      THIO/ATR received 5 mg.kg-1 thiopentone plus 0.05 mg.kg-1 atracurium for
      precurarization, and Group PROP received 2.5 mg.kg-1 propofol. All patients
      received 3 micrograms.kg-1 fentanyl and 1.5 mg.kg-1 succinylcholine. Time for
      induction of anaesthesia was recorded, and, after inserting a Grass Force
      Transducer between upper and lower incisors, jaw tone and the time course of jaw
      tension was recorded before and after the administration of succinylcholine.
      RESULTS: No differences in the onset of sleep were observed among the three
      groups (Group THIO 33 +/- 2 sec: THIO/ATR 30 +/- 2 sec: PROP 35 +/- 2 sec, mean
      +/- SE). Masseter preloads following induction of anaesthesia were similar in all
      three groups (THIO 16.4 +/- 2.1 N: THIO/ATR 15.1 +/- 2.0 N: PROP 12.7 +/- 1.6 N).
      However, after administration of succinylcholine, the increase in masseter tone
      was less in Groups PROP (5.0 +/- 1.1 N) and THIO/ATR (6.4 +/- 2.1 N) than in
      Group THIO (12.4 +/- 3.0 N; P < 0.05). CONCLUSION: Jaw tension after
      administration of succinylcholine is influenced by the choice of induction agent.
      The increase of masseter muscle tone is lower following propofol or
      thiopentone/atracurium induction than with thiopentone alone.

PMID- 9598256
TI  - Electrocardiographic monitoring in healthy young adult outpatients: mandatory or
      optional?
AB  - PURPOSE: To determine the incidence and duration of ECG abnormalities in healthy
      adults during short duration outpatient surgery and their relationship to
      important clinical events. METHOD: In 381, ASA Class I, day surgery patients
      undergoing short surgical procedures the ECG was monitored prospectively for
      evidence of abnormalities. The attending anaesthetist administered the
      anaesthetic and made all clinical decisions while relying on routine monitors
      (ECG, oximeter, BP, capnometer, oxygen analyser, low pressure alarm and
      anaesthetic gas monitors). Intra-operative events of clinical significance (e.g.,
      light anaesthesia, regurgitation, coughing, hypotension, arterial desaturation,
      hiccoughs etc), ECG abnormalities and their duration were documented. RESULTS:
      Electrocardiographic abnormalities were detected in 21% of patients as follows:
      sinus tachycardia (11%), artifacts (7%), premature atrial contractions (1.6%),
      lead disconnects (1%), sinus bradycardia (0.5%) and premature ventricular
      contractions (0.3%). All abnormalities resolved spontaneously within three
      minutes. Intra-operative incidents of consequence occurred in only 2.6%: light
      anaesthesia (5), arterial desaturation > 5% (2), hypotension (1), hiccough (1)
      and regurgitation (1). All incidents were detected clinically and by pulse
      oximetry. The ECG did not detect any of the incidents and was normal during the
      events. CONCLUSION: Routine ECG monitoring did not detect intra-operative
      incidents in healthy adults during short outpatient procedures. Detected ECG
      abnormalities were benign and resolved spontaneously within three minutes. Firm
      conclusions as to the safety implications of withdrawing ECG monitoring cannot be
      drawn from this study. Guidelines may need to be reviewed to determine whether
      ECG monitoring in such cases should be optional rather than mandatory.

PMID- 9598257
TI  - Comparative effects of desflurane and isoflurane on recovery after long lasting
      anaesthesia.
AB  - PURPOSE: Increasing the duration of exposure could lead to amplification of the
      pharmacokinetic differences between halogenated anaesthetic agents. The aim of
      our study was to compare anaesthesia recovery after desflurane and isoflurane,
      administered for more than three hours. METHODS: After informed consent, patients
      were randomly assigned to either desflurane (n = 15) or isoflurane (n = 15)
      groups. At the end of surgery, halogenated agents were discontinued and fresh gas
      flow was increased to 6 l.min-1 oxygen 100%. RESULTS: Mean anaesthesia duration
      was 292 +/- 63 and 304 +/- 91 min in the desflurane and isoflurane groups
      respectively. After desflurane and isoflurane discontinuation, the time to
      opening eyes was 12 +/- 7 and 24 +/- 11 min respectively (P < 0.001); to squeeze
      fingers at command was 17 +/- 11 and 35 +/- 19 min (P < 0.001); to extubation was
      16 +/- 6 and 33 +/- 13 min (P < 0.001); to give their name was 22 +/- 12 and 43
      +/- 21 min (P < 0.001); to achieve a Steward score of 6 was 28 +/- 16 and 57 +/-
      33 min (P < 0.001), to be fit for discharge from the recovery room was 46 +/- 19
      and 81 +/- 37 min (P < 0.003). Ranges of times to reappearance of recovery
      variables in the desflurane group were less than those after isoflurane (P <
      0.05). CONCLUSION: After long duration anaesthesia lasting up to three hours,
      desflurane allowed recovery and extubation in approximately half the time
      required by isoflurane. Less variability in results suggests better
      predictability of recovery with desflurane.

PMID- 9598258
TI  - Comparison of tramadol and morphine via subcutaneous PCA following major
      orthopaedic surgery.
AB  - PURPOSE: To compare subcutaneous PCA tramadol with subcutaneous PCA morphine for
      postoperative pain relief after major orthopaedic surgery and for the incidence
      of side-effects. METHODS: In a double-blind randomised controlled study 40
      patients (20 in each group) self-administered either tramadol or morphine for 72
      hr after surgery via s.c. PCA. The following variables were recorded at various
      time intervals: (i) pain score by means of a visual analogue scale, (ii) drug
      consumption and total PCA demands, (iii) vital signs (blood pressure and heart
      rate), (iv) oxygen saturation and respiratory rate, and (v) side-effects
      (sedation, nausea/vomiting, pruritus, urinary retention and constipation).
      RESULTS: Both drugs provided effective analgesia. The mean consumption in the
      first 24 hr was 792 +/- 90 mg tramadol and 42 +/- 4 mg morphine. Thereafter,
      consumption of both drugs declined markedly. Moderate haemodynamic changes were
      observed in both the tramadol and morphine groups (with a maximum 20% decrease in
      mean blood pressure and a maximum 17% increase in heart rate) during the 72 hr
      period. Both tramadol and morphine were associated with a clinically and
      statistically significant (P < 0.001) decrease in oxygen saturation, but without
      changes in respiratory rates. Desaturation was less marked with tramadol.
      Tramadol appeared to cause more nausea and vomiting than morphine. Sedation was
      mild and only seen during the first few hours after surgery in both groups.
      CONCLUSION: Tramadol is an effective analgesic agent for the relief of acute
      postoperative pain when administered by PCA via the subcutaneous route. Under
      these conditions tramadol behaves much like morphine with a similar side-effect
      profile.

PMID- 9598259
TI  - Volume kinetics of Ringer's solution and dextran 3% during induction of spinal
      anaesthesia for caesarean section.
AB  - PURPOSE: To study how the body handles fluid given intravenously during the onset
      of spinal anaesthesia in women scheduled for Caesarean section. METHODS: The
      effect of spinal anaesthesia on the volume kinetics of a constant-rate infusion
      of 25 ml.kg-1 of Ringer's solution (n = 11) and 10 ml.kg-1 of dextran 3% 60 (n =
      8) was studied before elective Caesarean section. Measurements of the blood
      haemoglobin concentration and urine excretion served as input variables in
      calculations of the size(s) of the body fluid spaces expanded by the infused
      fluid. The blood glucose level was also monitored. RESULTS: When a one-volume
      kinetic model were fitted to the data, spinal anaesthesia reduced the size of the
      expanded body fluid space by 30% (Ringer's) and 58% (dextran) (P < 0.02) When a
      two-volume model was statistically justified, anaesthesia reduced the rate of
      fluid equilibration between the two expanded body fluid spaces by 47% and 19%,
      respectively (P < 0.04) The baseline volume for the primary (central) fluid space
      was smaller than the expected plasma volume; 1.5 l for Ringer's solution and 0.9
      l for dextran. Only small changes in the blood glucose concentration were found.
      CONCLUSION: The onset of spinal anaesthesia induces acute changes in the body's
      handling of infused fluid that can be described by volume kinetic analysis.

PMID- 9598261
TI  - Monitoring evoked potentials during spinal surgery in one institution.
AB  - PURPOSE: To review the experience of one tertiary care institution with
      somatosensory evoked potential (SSEP) monitoring during spinal surgery in order
      to assess the ability to monitor and predict neurological outcome effectively.
      METHODS: Records of all patients undergoing spinal surgery during 18 mo were
      retrospectively reviewed. Information from the patient chart included
      preoperative neurological status, surgical procedure, anaesthetic management, and
      postoperative neurological outcome. Information regarding the techniques used and
      interpretation of all SSEP tracings were obtained from evoked potential data
      sheets completed for each patient. The incidences of clinically important SSEP
      changes and new postoperative neurological deficits were analysed. RESULTS:
      Somatosensory evoked potential monitoring of the lower and upper extremities with
      non invasive techniques was used in 309 patients undergoing surgery on the
      cervical (88), thoracic (52), and lumbar spine (169). Thirty seven patients (11%)
      did not have suitable tracings for interpretation and 17 (5.5%) had baseline
      tracings described as poor. An intraoperative SSEP change occurred in 16 patients
      (6%) with SSEP and seven (2.6%) had a new neurological deficit postoperatively.
      Three persistent deficits were predicted by permanent SSEP change, and one
      transient deficit by a transient SSEP change. False positive results occurred in
      12 patients (4.4%) and false negative results occurred in three (1.1%), with a
      sensitivity of 57% and a specificity of 95%. The incidence of SSEP changes was
      greater in the thoracic (18%) than in the cervical (1.2%) or lumbar (5.4%) groups
      (P < 0.05). CONCLUSION: Effective SSEP monitoring was possible despite the many
      factors which may have interfered with monitoring. More improvements in the
      techniques and conditions of monitoring are needed to decrease the incidence of
      false positive and negative results.

PMID- 9598260
TI  - Obstetrical anaesthesia for a parturient with preeclampsia, HELLP syndrome and
      acute cortical blindness.
AB  - PURPOSE: To report the management of a multigravida presenting with preeclampsia,
      HELLP syndrome and acute cortical blindness for Caesarean section. CLINICAL
      FEATURES: A 39-yr-old woman, with three past uncomplicated pregnancies presented
      at 33 wk with acute cortical blindness. Based on clinical and laboratory
      assessment, a diagnosis of preeclampsia with HELLP syndrome was made. A CT scan
      of her head demonstrated ischaemic lesions of her basal ganglia, extending
      superiorly to involve both posterior parietal and occipital regions. Infusions of
      magnesium sulphate and hydralazine were started and an urgent Caesarean section
      was performed under subarachnoid anaesthesia after insertion of an arterial line
      and intravenous hydration. The course of anaesthesia and surgery was uneventful
      and she delivered a live 1540 g female infant. By the following morning, she had
      recovered some vision and visual recovery was complete by 72 hr postpartum. She
      underwent an MRI with angiography on the first postpartum day. Ischaemic lesions
      were confirmed in the same sites identified on CT scan but all major cerebral
      vessels were patent and no significant vascular abnormality was noted. Her
      postoperative course was uneventful and she was discharged home seven days
      postpartum after being prescribed labetalol for continued hypertension.
      CONCLUSION: The anaesthetic management of a parturient with acute cortical
      blindness and HELLP syndrome is modeled on the underlying preeclamptic condition.
      Invasive monitoring is not routinely indicated but is specifically indicated in
      some cases. Provided that it is not contraindicated because of prohibitive risk
      to the mother, regional anaesthesia has particular advantage in these patients.
      In particular, the use of spinal anaesthesia, which has been discouraged by some
      for this patient population, should be re-evaluated.

PMID- 9598262
TI  - Nonlinear additivity of nitrous oxide and isoflurane potencies in rats.
AB  - PURPOSE: To test the hypothesis that the MAC values of nitrous oxide (N2O) and
      isoflurane were not linearly additive, as theorized by the postulated mode of
      action based on lipid solubility, in a rat model. METHODS: Eight Long Evans rats
      were randomly assigned to order of measurement of MAC for isoflurane and N2O
      alone and in combination using standard 45 sec supramaximal electrical
      stimulation (50 volts x 10 msec duration pulses at 50.sec-1 applied for 45 sec
      s.c. to the lower abdominal groin area). The MAC of N2O was measured at
      hyperbaric compression to 2.25 atmospheres absolute, 1710 mmHg. RESULTS: The MAC
      values found were: isoflurane -0.98 +/- 0.12 and N2O - 159 +/- 12 volume (vol)%,
      or 1.59 +/- 0.12 atmospheres absolute (ATA) (All values are mean +/- standard
      deviation). The linear additivity theory suggests % MAC agent A + % MAC agent B =
      1.0. However, % MAC isoflurane + % MAC N2O = 1.37 +/- 0.15 (P < .001).
      CONCLUSION: Nonlinear additivity was demonstrated with direct MAC measurement for
      both isoflurane and N2O in rats. This suggests an agonist-antagonist
      relationship.

PMID- 9598263
TI  - Inhibition by diazepam of ketamine-induced hyperlocomotion and dopamine turnover
      in mice.
AB  - PURPOSE: To investigate the effects of the benzodiazepine diazepam on ketamine
      induced hyperlocomotion and dopamine turnover. METHODS: Adult male ddY mice were
      used (n = 218). Locomotor activity was measured with four circular activity cages
      equipped with three photocell sensor units. Interruptions by a mover of the
      infrared light Peams were recorded on electromechanical counters, and
      automatically printed every 10 min for three hours after the ketamine injection.
      All drugs were administered intraperitoneally (i.p.). The concentrations of
      dopamine and its metabolites in discrete brain regions were measured by high
      performance liquid chromatography with electrochemical detection. RESULTS:
      Ketamine (30 mg.kg-1) increased total locomotor activity counts for three hours
      to 442% of control in mice (P = 0.0001). Diazepam, 3 and 10 mg.kg-1, inhibited,
      in a dose-dependent fashion, this ketamine-induced hyperlocomotion by 26% (P =
      0.0111) and 59% (P = 0.0001), respectively. Regional brain dopamine assays
      revealed that ketamine (30 mg.kg-1) increased the homovanillic acid:dopamine
      ratio (one indicator of dopamine turnover) to 121% of control in the nucleus
      accumbens (P = 0.0065) and to 111% in the striatum (P = 0.0135) at peak
      locomotion. Diazepam, 3 and 10 mg.kg-1, returned this increase in dopamine
      turnover produced by ketamine to control levels both in the nucleus accumbens (P
      = 0.0061 and P = 0.0117, respectively) and in the striatum (P = 0.0004 and P =
      0.0047, respectively). CONCLUSION: These results suggest that the inhibition by
      diazepam of ketamine-induced hyperlocomotion may be related to its ability to
      suppress the activation of dopamine neurons in the nucleus accumbens and
      striatum.

PMID- 9598264
TI  - Lower oesophageal sphincter tone increases after induction of anaesthesia in pigs
      with full stomach.
AB  - PURPOSE: The lower oesophageal sphincter (LOS) is the man mechanism that prevents
      gastro-oesophageal regurgitation during anaesthesia. The aim of this study was to
      assess the effect on lower oesophageal sphincter pressure (LOSP) of rapid
      sequence induction in pigs with full stomachs. METHODS: Lower oesophageal
      sphincter pressure and oesophageal barrier pressure (BrP = LOSP minus gastric
      pressure) were measured using a water-perfused manometric catheter method in 12
      pigs after gastric filling with 500 ml of liquid nutrient mixture. Six pigs were
      randomly allocated to receive 5 mg.kg-1 propofol and 3 mg.kg-1 succinylcholine
      i.v. and six pigs received 8 mg.kg-1 thiopentone and 3 mg.kg-1 succinylcholine
      i.v. RESULTS: After induction, mean LOSP increased during the period with
      fasciculations from 19 +/- 4 mmHg to 28 +/- 5 mmHg in the propofol
      succinylcholine group and from 23 +/- 6 mmHg to 36 +/- 7 mmHg in the thiopentone
      succinylcholine group. The LOSP remained elevated after the fasciculations. LOSP
      and BrP were not different between the groups. CONCLUSIONS: Induction of
      anaesthesia with propofol-succinylcholine or thiopentone-succinylcholine
      increases LOSP and, consequently, BrP in pigs with a full stomach. This increase
      begins before fasciculations and remains elevated for the period when intubation
      would occur.

PMID- 9598265
TI  - An evaluation of a modified Macintosh laryngoscope in a manikin.
AB  - PURPOSE: In this manikin study a modified Macintosh blade was prospectively
      compared with its original focussing on the forces exerted on the maxillary
      incisor teeth and intubation success. The modified blade, a standard Macintosh
      blade with a reduced proximal flange, was intended to reduce the forces exerted
      on the maxillary incisors. METHODS: A manikin equipped with two sensors, to
      measure forces applied to the maxillary incisors in the axial and the transverse
      direction, was used. Fourteen staff anaesthetists and 16 residents each performed
      two laryngoscopies with both blades. RESULTS: All laryngoscopies resulted in
      successful tracheal intubation. The maximal and mean forces exerted on the teeth
      in the axial direction were 12 N and 5.8 N smaller (P < 0.0005 and P < 0.0005,
      respectively) when the modified blade was used. CONCLUSION: The use of the
      modified blade resulted in a reduction of the forces on the maxillary incisors
      whereas the intubation success rate was the same as with the original. Studies in
      manikins can be useful in comparative laryngoscope testing.

PMID- 9598266
TI  - Combined spinal epidural anaesthesia in a primigravida with valvular heart
      disease.
AB  - PURPOSE: This is the first report describing combined spinal epidural anaesthesia
      for labour and unexpected Caesarean section in a patient with mitral and aortic
      stenosis and insufficiency. CLINICAL FEATURES: The patient was a 30-yr-old GIPO
      with a history of rheumatic fever. She had moderate stenosis and insufficiency of
      the mitral and aortic valves. Combined spinal epidural anaesthesia was used
      throughout labour and subsequent Caesarean section. The patient remained
      haemodynamically stable throughout the procedure. CONCLUSION: Carefully planned
      regional anaesthesia was safely used for labour and operative delivery in this
      parturient with mitral and aortic valvular disease.

PMID- 9598267
TI  - ATP-induced ventricular asystole and hypotension during endovascular stenting
      surgery.
AB  - PURPOSE: To describe four cases of endoluminal stenting surgery in which
      adenosine 5'-triphosphate (ATP) was used to arrest the heart for accurate
      placement of the stent-graft. CLINICAL FEATURES: Four patients with descending
      thoracic aortic aneurysm were anaesthetized for deployment of a self-expanding
      stent-graft. Maintenance of general anaesthesia was performed with isoflurane and
      nitrous oxide in three patients, and with fentanyl and propofol in another. An
      initial trial of 20 mg ATP was administered via a central venous catheter as
      rapidly as possible, and produced third degree AV block of 8 +/- 1.7 sec and 59.7
      +/- 17.5 sec hypotension, mean blood pressure < 60 mmHg, in three patients. The
      time to onset of AV block was 15.7 +/- 6.7 sec. In these patients, deployment of
      the stent-graft was performed during ventricular asystole produced by 30 mg ATP,
      which produced 16.3 +/- 2.1 sec third and second degree AV block. In one patient
      anaesthetized with fentanyl and propofol, 20 mg ATP did not change AV conduction.
      However, after 10 mg edrophonium, 20 mg ATP produced 9 sec third degree AV block.
      In all cases, heart rate and PQ interval were restored to the pre-drug control
      level within 50 sec after the commencement of AV block. There were no clinical
      complications related to this procedure in any patient. CONCLUSION: ATP is a
      convenient and suitable agent to produce transient ventricular asystole for the
      precise deployment of a self-expanding stent-graft. Co-administration of a
      parasympathomimetic agent might potentiate the inhibitory effect of ATP on AV
      conduction.

PMID- 9598268
TI  - Persistent perioperative laryngospasm in a patient with Parkinson's disease.

PMID- 9598269
TI  - Another potential problem with the hidden i.v.

PMID- 9598270
TI  - Physostigmine, propofol and the GABAA receptor.

PMID- 9598271
TI  - Current status of genetic studies of Gilles de la Tourette syndrome.
AB  - Gilles de la Tourette syndrome (TS) is a familial, neuropsychiatric disorder
      characterized by chronic, intermittent motor and vocal tics. Despite strong
      evidence for a genetic basis of this disorder from family, twin, and adoption
      studies, no convincing evidence for genetic linkage has been reported. Numerous
      groups world-wide have searched for genetic susceptibility factors for TS,
      testing specific candidate genes in neurotransmitter systems as well as DNA
      markers with known locations. Several factors may complicate the search for genes
      for this disorder, including diagnostic uncertainties, definition of the TS
      phenotypic spectrum as it relates to genetic susceptibility, assortative mating,
      genetic heterogeneity, and unclear mode of inheritance. In this article, we
      review the evidence for the genetic basis of TS and the current status of genetic
      studies.

PMID- 9598272
TI  - Coming alive: the psychotherapeutic treatment of patients with eating disorders.
AB  - OBJECTIVE: To describe a dynamic psychotherapeutic approach specifically
      developed for women with eating disorders. METHOD: The developmental origins and
      psychological disturbances associated with eating disorders are outlined based on
      a review of the literature and the authors' observations. Principles from
      contemporary psychodynamic theories that focus on subjectivity and
      intersubjectivity are applied to the treatment of women with eating disorders and
      are illustrated with clinical vignettes. Theoretical models employed include
      intersubjective and relational theory, self psychology, and feminist
      psychodynamic theory. RESULTS: Relative unresponsiveness to a child's subjective
      experience and to child-initiated cues are thought to contribute to psychological
      disturbances among women with eating disorders. These disturbances include
      impairment in the sense of effectiveness, in the capacity to appreciate and
      tolerate emotions, and in the continuity and cohesiveness of self-experience.
      Self-imposed starvation, binge-purge episodes, and excessive exercise may act as
      psychic organizers in women with these vulnerabilities. An active
      psychotherapeutic approach with sustained interest in the patient's authentic
      subjective experience promotes the identification, organization, and integration
      of emotional experience and the consolidation of a more differentiated sense of
      self. CONCLUSION: In the psychotherapeutic treatment of women with eating
      disorders, a therapeutic posture of sustained empathic enquiry contributes to the
      patient's curiosity about her own subjective world. Feeling understood in a
      therapeutic relationship and feeling assisted in organizing and understanding
      one's subjective experience contributes to the gradual unfolding of the
      psychological sense of self.

PMID- 9598273
TI  - The meaning of body image for women with eating disorders.
AB  - OBJECTIVE: To propose a theoretical model accounting for the meaning and function
      of body image disturbances for individuals with eating disorders. This model
      departs from available conceptualizations of body image focused on attractiveness
      and emphasizes the role of body image preoccupations in the regulation of self
      esteem and affect. METHOD: This model was developed on the basis of the author's
      clinical observations and the available empirical research. RESULTS: Three main
      functions of body image are described. The first one, "affiliation," consists of
      using one's appearance in the establishment of interpersonal relationships, both
      at the level of friendship and romance. The second function, "avoidance,"
      consists of using one's body image to avoid abuse, be it psychological, physical,
      or sexual. The third function, "expression," consists of using one's body image
      to communicate to the self and others one's capacity for accomplishment or one's
      inner feelings of dejection. CONCLUSION: This model is designed to be a
      therapeutic tool within body image therapy. Body image therapy can be most
      effective when focused on the unique meaning of body image for each individual
      patient.

PMID- 9598274
TI  - A group therapy approach to facilitate integration of risk information for women
      at risk for breast cancer.
AB  - OBJECTIVE: To describe and illustrate elements of a group counselling approach
      designed to enhance the communication of risk information on breast cancer (BC)
      to women with a family history of this disease. Breast cancer is a leading cause
      of female cancer death. The most important risk factor for BC is a positive
      family history in at least 1 first-degree relative, and approximately one-third
      of women with BC have a family history of the disease. Recent evidence suggests
      that there is a significant psychological impact associated with having a family
      history of BC, and this may influence the psychological adjustment and response
      to being counselled for personal risk. New counselling approaches are required.
      METHOD: This paper describes a group therapy approach that incorporates
      principles of supportive-expressive therapy designed to address the emotional
      impact of being at risk for BC and to promote accuracy of perceived risk. The key
      elements of the intervention are described along with clinical illustrations from
      groups that are part of an ongoing study to develop and standardize the group
      therapy. CONCLUSION: Qualitative data from the groups suggest that this model of
      therapy is both feasible and effective.

PMID- 9598275
TI  - Affect and marital adjustment in women's rating of dyspareunic pain.
AB  - OBJECTIVE: To investigate the extent to which depressive symptomatology, anxiety,
      and marital adjustment mediate pain ratings in women suffering from dyspareunia.
      METHOD: Seventy-six women with dyspareunia were administered the depression and
      anxiety scales of Derogatis's Brief Symptom Inventory and the McGill Pain
      Questionnaire. They also underwent a manual-visual gynecological examination, an
      ultrasound, and a colposcopy in an attempt to identify potential evidence and
      type of organicity. RESULTS: Depressive symptomatology, anxiety, and marital
      adjustment together accounted for a significant amount of the variance in pain
      ratings, although only anxiety and marital adjustment were independent predictors
      of pain ratings in the entire group of women with dyspareunia. When multiple
      regression analyses were then applied to different diagnostic subgroups of
      dyspareunia, the independent predictors of pain rating varied depending on the
      findings from the gynecological examinations. CONCLUSION: Affect and marital
      adjustment appear to be significant predictors of dyspareunic pain rating,
      although the independent contribution of psychosocial variables may vary
      depending on the presence and type of organic findings.

PMID- 9598276
TI  - Geriatric psychiatry outreach practices in the province of Ontario: the role of
      the psychiatrist.
AB  - OBJECTIVE: To determine the mode of practice of multidiscliplinary and
      interdisciplinary teams in the field of geriatric psychiatry in the province of
      Ontario with specific reference to the role of the psychiatrist on the teams.
      METHOD: Teams were identified, and a simple questionnaire was developed and
      submitted to every team at an annual conference. RESULTS: Responses were obtained
      from 38 out of 47 teams. The composition of the teams is variable as regards size
      and represented discliplines. Nine teams do not have psychiatrists directly
      affiliated with them. Eighteen teams, 4 of which are based in teaching hospitals,
      have fewer than 1 full-time equivalent (FTE) psychiatrist. Among these teams, 4
      have fewer than 0.1 FTE psychiatrist and 10 have fewer than 0.5 FTE psychiatrist.
      Eleven teams include between 1 and 1.5 FTE psychiatrists on their staff. Four
      teams (10.5%) require that the initial assessment of all patients be undertaken
      by a psychiatrist. In 18 (47%) of the teams, assessment by a psychiatrist can be
      infrequent or nonexistent. Discussion of the referral with a psychiatrist occurs
      in the majority of teams, but in a significant minority (10 [27%]), this occurs
      quite infrequently or not at all. CONCLUSION: Geriatric psychiatry outreach
      practices in Ontario involve many different disciplines in the assessment and
      follow-up of geriatric psychiatry patients, often without the ready availability
      of psychiatric input. We applaud the expanding roles of different disciplines in
      this practice. We are concerned, however, at the paucity of psychiatrists working
      in this field.

PMID- 9598278
TI  - Supervision of termination in psychotherapy.
AB  - OBJECTIVE: To propose a model for teaching and supervising the termination
      process in psychoanalytic psychotherapy. METHOD: Group supervision of the 12-week
      termination phase of psychotherapy with a patient who had been in psychotherapy
      with a senior resident for 2 years. RESULTS: This supervisory method provided a
      positive termination experience for the patient and valuable group-teaching
      experience for residents at various levels in their training. CONCLUSION: A group
      supervisory teaching process is a particularly effective way of teaching the
      termination process and is more efficient in terms of time, energy, and
      dissemination of knowledge than a traditional one-on-one supervision model.

PMID- 9598277
TI  - Therapy with lesbian couples: the issues and the interventions.
AB  - OBJECTIVE: To highlight difficulties that are unique to lesbian couples by
      reviewing the data that contrast lesbian and heterosexual couples and exploring
      the theories that explain the observed differences in couple dynamics. METHOD: A
      review of the literature contrasting demographics and relationship
      characteristics in lesbians and heterosexual couples was conducted, and a review
      of lesbian psychotherapy literature was performed. RESULTS: The differences in
      couple dynamics may be attributed to female relational styles and the stresses of
      being in a relationship that is not socially sanctioned (homophobia).
      CONCLUSIONS: Therapists should not use heterosexual standards when evaluating
      lesbian relationships because this may lead to misconstruance of a couple's
      emotional intensity as pathological. They should, however, recognize the problems
      that stem from pathological levels of fusion. When evaluating a couple,
      clinicians must assess the level of internalized homophobia so as to understand
      when the couple's difficulties originate from unresolved conflicts over sexual
      orientation.

PMID- 9598280
TI  - Risky business: making sense of estimates of risk.
AB  - This article describes various indices of risk, which is the probability that a
      person will develop a specific outcome. The risk difference is the absolute
      difference in risks between 2 groups and can be used either to compare the
      outcome of 2 groups, one of which was exposed to some genetic or environmental
      factor, or to see how much of an effect a treatment may have. The reciprocal of
      the risk difference, the number needed to treat, expresses how many patients must
      receive the intervention in order for 1 person to derive some benefit.
      Attributable risk reflects the proportion of cases due to some putative cause and
      indicates the number of cases that can be averted if the cause were removed.
      Finally, the relative risk and odds ratio reflect the relative differences
      between groups in achieving some outcome, either good (a cure) or bad
      (development of a disorder).

PMID- 9598279
TI  - [Deinstitutionalization in psychiatry: revising our principles of community
      psychiatry or failure of deinstitutionalization!].
AB  - OBJECTIVE: To update community psychiatry principles within the context of
      increased outpatient services. METHOD: Analysis of the evolution of some
      community models in Italy, France, Holland, and the United States. RESULTS:
      Deinstitutionalization was aimed to protect patients from the harmful effects of
      mental hospitals but failed to result in social integration for many of them.
      Success and failure of community practice shed a new light on the diversity and
      constancy of patients' needs. CONCLUSIONS: Quality-of-life improvement and
      services integration should be guided by planning and selection of the required
      services.

PMID- 9598281
TI  - Seizure on low-dose clozapine.

PMID- 9598282
TI  - Re: Psychiatric presentation of adolescent homosexuality.

PMID- 9598283
TI  - Combination of risperidone and donepezil in Lewy body dementia.

PMID- 9598284
TI  - Improving the diagnosis of bipolar disorder.

PMID- 9598285
TI  - Gabapentin in geriatric psychiatry patients.

PMID- 9598286
TI  - Intraventricular tumor (astrocytoma) associated with an organic psychosis.

PMID- 9598287
TI  - The discoverers of the therapeutic effect of chlorpromazine in psychiatry: qui
      etaient les vrais premiers praticiens?

PMID- 9598288
TI  - Cutaneous findings of connective tissue disease.
AB  - This review provides the generalist with a simple means of approaching the
      diagnosis and treatment of connective tissue diseases. A concise summary of
      autoimmune laboratory panels and their relevance in the diagnosis of Lupus,
      Dermatomyositis, Mixed Connective Tissue Disease, and Sclerodermatous Diseases is
      provided.

PMID- 9598289
TI  - Rational management of chronic abdominal pain.
AB  - Patients presenting with chronic abdominal pain are a diagnostic and therapeutic
      challenge. Recent advances in classification of the various chronic abdominal
      pain disorders and recent evidence supporting the advantages of adopting a
      multimodal therapeutic approach can often prove quite helpful.

PMID- 9598290
TI  - Recent findings in asthma likely to impact patient care.
AB  - The management of asthma is becoming increasingly complex as more pharmacologic
      agents become available and we gain increased understanding of the pathogenetic
      processes of asthma and the risks for potentially irreversible airway remodeling
      that might be increased by suboptimal management and interactions with
      concomitant disease states such as gastroesophageal reflux. Although physicians
      now have greater responsibility to make use of this increasing knowledge to
      provide more effective management for their asthma patients, they also have a
      greater opportunity to increase the overall quality of life of patients under
      their care.

PMID- 9598292
TI  - Nutrition & coronary heart disease.

PMID- 9598291
TI  - Update on headache.
AB  - The late 1990s have witnessed an unprecedented growth in understanding of the
      pathophysiology of headache and treatment options. This article will briefly
      review the current pathophysiology and classification scheme, and will focus on
      abortive and preventative options in the treatment of headache.

PMID- 9598293
TI  - Physician practice control in the era of managed care.

PMID- 9598294
TI  - Ribosomal tRNA binding sites: three-site models of translation.
AB  - The first models of translation described protein synthesis in terms of two
      operationally defined tRNA binding sites, the P-site for the donor substrate, the
      peptidyl-tRNA, and the A-site for the acceptor substrates, the aminoacyl-tRNAs.
      The discovery and analysis of the third tRNA binding site, the E-site specific
      for deacylated tRNAs, resulted in the allosteric three-site model, the two major
      features of which are (1) the reciprocal relationship of A-site and E-site
      occupation, and (2) simultaneous codon-anticodon interactions of both tRNAs
      present at the elongating ribosome. However, structural studies do not support
      the three operationally defined sites in a simple fashion as three
      topographically fixed entities, thus leading to new concepts of tRNA binding and
      movement: (1) the hybrid-site model describes the tRNAs' movement through the
      ribosome in terms of changing binding sites on the 30S and 50S subunits in an
      alternating fashion. The tRNAs thereby pass through hybrid binding states. (2)
      The alpha-epsilon model introduces the concept of a movable tRNA-binding domain
      comprising two binding sites, termed alpha and epsilon. The translocation
      movement is seen as a result of a conformational change of the ribosome rather
      than as a diffusion process between fixed binding sites. The alpha-epsilon model
      reconciles most of the experimental data currently available.

PMID- 9598295
TI  - Developmental toxicity of diglyme by inhalation in the rat.
AB  - Diglyme (Diethylene glycol dimethyl ether, CAS No. 111-96-6) is a glycol ether
      which has been used in solvent formulations. To assess the potential
      developmental toxicity of this chemical, groups of pregnant Crl:CD BR rats were
      exposed to either 0 (control, room air only), 25, 100, or 400 ppm diglyme by
      inhalation for 6 hrs/day for Days 7 through 16 or gestation (day on which the
      copulation plug was detected was designation Day 1 G). All female rats were
      euthanized on day 21G and the fetuses were examined. An additional group of rats
      was treated with 25 ppm 2-methoxethanol (2ME) to serve as a positive control and
      for comparison of relative potencies. Maternal toxicity evident as depressed feed
      consumption at 400 ppm and increased liver weights at 100 ppm. There were no dams
      in the 400 ppm group with live fetuses (all litters consisted on resorbed
      conceptuses). Embryo viability was unaffected by concentrations of diglyme as
      high as 100 ppm. 2ME produced increased liver weights and depressed feed
      consumption at 25 ppm. Embryo-fetal toxicity was evident as a concentration
      related decrease in fetal weight at diglyme concentrations as high as 100 ppm
      (and with 2ME). There were no fetuses derived from the 400 ppm diglyme-treated
      dams. A low incidence of structural malformations was observed in all diglyme
      groups (as well as with 2ME). The incidence of variations, (primarily delayed
      skeletal ossification and rudimentary ribs) was increased in the 25 and 100 ppm
      diglyme groups. The incidence and severity in the diglyme and 2ME groups exposed
      to 25 ppm was essentially the same suggesting similar potency for producing
      structural variations. In this study, diglyme was embryolethal at 400 ppm; a
      level that otherwise was only marginally toxic to the dam. Maternal and fetal
      toxicity also were demonstrated at 100 ppm. Although the fetal defects detected
      following diglyme exposure at 25 ppm were not significantly different from
      control values (with the exception of the incidence of skeletal developmental
      variations), the pattern, type, and incidence of variations were similar to those
      seen at 100 ppm, suggesting that 25 ppm was an effect level that approaches the
      lower end of the developmental toxicity response curve. Therefore, the no
      observable-effect level (NOEL) for diglyme exposure in the dam is 25 ppm and a
      NOEL was not clearly demonstrated for the conceptus.

PMID- 9598296
TI  - Cardiac sensitization testing of the halon replacement candidates
      trifluoroiodomethane (CF3I) and 1,1,2,2,3,3,3-heptafluoro-1-iodopropane (C3F7I).
AB  - Trifluoroiodomethane (CF3I) and 1,1,2,2,3,3,3-heptafluoro-1-iodopropane (C3F7I)
      have been considered as replacement candidates for halon fire suppressants due to
      their excellent fire extinguishant capabilities and low ozone depletion potential
      compared to halon fire extinguishants in use currently. As part of the process to
      develop environmental and health effects criteria for halon substitutes, a
      cardiac sensitization test was conducted in beagle dogs. Cardiac sensitization to
      adrenaline is a phenomenon associated with the inhalation of a number of
      unsubstituted and halogenated hydrocarbons. Adrenaline was administered by
      intravenous injection before and during inhalation of the test substance. CF3I
      was administered to dogs at concentrations in air of 0.1, 0.2, 0.4 or 1% v/v. At
      each of 0.4 and 1.0% CF3I, the first dog exposed developed fatal ventricular
      fibrillation, and no further dogs were exposed at these concentrations. There was
      no cardiac sensitization at 0.1 or 0.2% CF3I. For the C3F7I experiment, dogs were
      exposed to concentrations in air of 0.1, 0.2 or 0.4% v/v. At each of 0.1 and 0.4%
      C3F7I, one dog responded with multifocal ventricular ectopic beats. Thus, CF3I
      and C3F7I are potent cardiac sensitizers in the adrenaline-challenged dog model.

PMID- 9598297
TI  - Preclinical oral toxicology in rats of D-002, a natural drug with antiulcer
      effects.
AB  - D-002 is a mixture of higher aliphatic primary alcohol isolated from bees wax
      (Apis mellifera) with effective antiulcer effects demonstrated in different
      experimental models. Oral toxicity of D-002 (5-5000 mg/kg) was evaluated in sub
      acute (14 days), subchronic (90 days) and chronic (1 year) studies in Sprague
      Dawley rats from both sexes. There was no treatment-related toxicity. Thus,
      effects on body weight, food consumption, clinical observations, blood
      parameters, organ weight ratios and histopathological findings were similar in
      control and treated groups. These short and long-term studies support a wide
      safety margin for this product.

PMID- 9598298
TI  - Preclinical toxicological evaluation of sertraline hydrochloride.
AB  - The toxicity profile of the antidepressant drug sertraline was determined in a
      series of preclinical studies in mice, rats, rabbits and dogs. Acute, subchronic,
      reproductive, chronic and carcinogenicity studies were conducted by the oral
      route. The highest doses tested in these studies were the maximum tolerated doses
      based on clinical signs, decreased food consumption, body weight effects, organ
      weight changes or clinical/anatomical pathology findings. Genetic toxicity
      studies were also performed. The liver was identified as a target organ in the
      mouse, rat and dog. The observed liver findings were consistent with hepatic
      xenobiotic-metabolizing enzyme induction and included hepatomegaly,
      hepatocellular hypertrophy, slightly increased serum transaminase activity and
      proliferation of smooth endoplasmic reticulum. Hepatocellular fatty change, a
      minimal toxic effect, was seen in mice and rats. There was no teratogenicity in
      studies conducted at maternally toxic doses in rats and rabbits. Decreased
      neonatal survival and growth observed in these studies have been previously
      reported in reproduction studies with other serotonin reuptake inhibitors.
      Sertraline was not genotoxic in an extensive battery of tests. Carcinogenicity
      tests were negative in rats, while benign liver tumors were slightly increased in
      drugtreated male mice. Liver tumors were considered secondary to the enzyme
      inducing potential of sertraline and not indicative of human risk.

PMID- 9598299
TI  - Minimal effects of acrylonitrile on pulmonary and hepatic cell injury enzymes in
      rats with induced cytochrome P450.
AB  - Acrylonitrile (AN) has many industrial applications but is a known carcinogen in
      animals and a suspect human carcinogen. Its toxicity is generally associated with
      its bioactivation, the initial step of which is epoxidation by cytochrome P450.
      While the hepatotoxicity and pneumotoxicity of AN in naive rats is generally low,
      the purpose of this study was to investigate the pneumotoxicity and
      hepatotoxicity of AN in adult male Sprague-Dawley rats and evaluate interactions
      with agents that may alter its metabolism. Five agents, phenobarbital, beta
      naphthoflavone, pyridine, ethanol, and acetone, were administered prior to AN as
      inducers of CYP2B, CYP1A, and CYP2E1. Pneumotoxicity was measured as increases in
      y-glutamyltranspeptidase (GGT) and lactate dehydrogenase (LDH) in bronchoalveolar
      lavage fluid (BALF). Hepatotoxicity was measured as increases in serum sorbitol
      dehydrogenase (SDH). AN (1 mmol/kg ip) had little effect on liver or lung, even
      when given following most of the inducing agents. AN (1.5 mmol/kg) caused an
      increase in GGT, but had little effect on SDH or LDH. Acetone plus AN caused an
      increase in mortality and some indication of pneumotoxicity, but lung and liver
      were histologically normal. Thus AN alone even at a high dose had no effect on
      the liver or lung and minimal effects following induction of cytochrome P450 by
      acetone.

PMID- 9598300
TI  - Contact hypersensitivity to dicyclohexylcarbodiimide and diisopropylcarbodiimide
      in female B6C3F1 mice.
AB  - Dicyclohexylcarbodiimide (DCC) and diisopropylcarbodiimide (DIC) are two commonly
      used coupling reagents in protein synthesis resulting in exposure of individuals
      in chemical and pharmaceutical industries as well as research laboratories
      involved in protein synthesis and recombinant DNA techniques. The objectives of
      these studies were to determine the irritation and sensitizing potential of these
      two compounds when applied topically to B6C3F1 mice. Sensitization potential was
      assessed by the Mouse Ear Swelling Test (MEST) and the murine Local Lymph Node
      Assay (LLNA). Concentrations used in the contact hypersensitivity assays were
      determined by primary irritancy studies. DCC and DIC were identified as both
      irritants and contact sensitizers with the MEST being a more sensitive indicator
      of sensitization potential. The MEST identified DCC as a sensitizer at
      concentrations as low as 0.006% (w/v) 24 hr and 48 hr post challenge and DIC at
      0.3% (w/v) and 1.5% (w/v) 24 and 48 hr post challenge, respectively. In the LLNA,
      the lowest concentrations yielding a significant response were 0.06% (w/v) for
      DCC and 10% (w/v) for DIC.

PMID- 9598301
TI  - Developmental toxicity of steviol, a metabolite of stevioside, in the hamster.
AB  - The developmental toxicity of steviol, a metabolite of stevioside, was studied in
      hamsters. Pregnant hamsters were intubated with steviol at dose levels of 0,
      0.25, 0.5, 0.75 and 1.0 g/kg BW/day on days 6-10 of gestation. Steviol at doses
      of 0.75 and 1.0 g/kg BW/day were highly toxic to both dams and fetuses.
      Significant decrease of maternal body-weight gain during the experimental period
      (days 6-14) and high percentage of maternal mortality indicated the general
      toxicity of these two high doses. The number of live fetuses per litter and mean
      fetal weight also significantly decreased in the steviol-treated animals at doses
      of 0.75 and 1.0 g/kg BW day. The animals treated with an intermediate dose (0.50
      g/kg BW/day) exhibited less signs of maternal and developmental toxicity than the
      two high doses (0.75 and 1.0 g/kg BW/day). One craniomeningocele was found in a
      fetus under the maternal toxic condition in steviol-treated at a dose of 0.75
      g/kg BW/day. Neither the skeleton nor visceral development of the offspring was
      affected by steviol treatment except delayed ossification of the xiphoid (bifid)
      and long bones of the limbs and supernumerary thoracic ribs (14th ribs) tended to
      be increased at doses of 0.5 to 1.0 g/kg BW/day steviol. No dose-related
      teratogenesis was detected. From the result of the present study concerning
      maternal toxic condition and embryotoxicity, an oral dose of 0.25 g steviol/kg
      BW/day is regarded as having no observable effect. This steviol-treated dose is
      derived from stevioside 625 mg/kg BW/day which is approximately 80 times higher
      than the suggested acceptable daily intake of stevioside for humans (7.938 mg/kg
      BW/day).

PMID- 9598302
TI  - Gastrointestinal absorption of metals.
AB  - Estimating gastrointestinal absorption remains a significant challenge in the
      risk assessment of metals. This presentation reviews our current understanding of
      the gastrointestinal absorption of lead (Pb) to illustrate physiological
      mechanisms involved in metal absorption, new approaches that are being applied to
      the problem of estimating metal absorption in humans, and issues related to
      integrating this information into risk assessment. Absorption of metals can be
      highly variable in human populations because it is influenced by a variety of
      factors that include the chemical form of the metal, environmental matrix in
      which the ingested metal is contained, gastrointestinal tract contents, diet,
      nutritional status, age, and, in some cases, genotype. Thus, in risk assessment
      models, gastrointestinal absorption is best described as a variable whose
      distribution is determined in part by the above multiple influences. Although we
      cannot expect to evaluate empirically each of the above factors in human
      populations, we can expect to achieve a sufficiently detailed understanding of
      absorption mechanisms to develop conceptual and, eventually, quantitative models
      of absorption that account for some aspects of individual variability. A
      conceptual model is presented of the physiological processes involved in the
      transfer of ingested metals from the lumen of the gastrointestinal tract to the
      blood circulation. Components of the model include delivery to the site(s) of
      absorption; distribution among intracellular and extracellular ligands and
      transcellular and paracellular pathways of transfer across the gastrointestinal
      tract epithelium. The gastrointestinal absorption of Pb is discussed in the
      context of this model.

PMID- 9598303
TI  - Characterization of gene expression in mouse blastocyst using single-pass
      sequencing of 3995 clones.
AB  - To study the gene expression profile in the mouse blastocyst and to identify
      embryonic stage-specific genes, we randomly selected cDNAs derived from mouse
      blastocysts and sequenced a total of 3995 clones from one or both ends. Excluding
      the uninformative clones, 3395 clones were grouped as 937 different kinds of
      genes. Among these, 465 and 406 species showed similarity to known genes and
      expressed sequence tags (ESTs), respectively, whereas 66 species showed no
      significant similarity to any genes in known databases. Analysis of these cDNAs
      revealed that this library contained a variety of functional genes as well as
      genes that have not been detected in the human EST database; it should provide us
      with a useful resource for molecular analysis of developmental mechanisms.
      Although the human EST project is considered to represent roughly half of all
      genes, our findings indicate that many early stage developmental genes remain to
      be identified.

PMID- 9598304
TI  - Transposition of RhoA to the murine Y chromosome.
AB  - In an effort to produce a more complete transcription map of the short
      (approximately 5 Mb) arm of the mouse Y chromosome, we have initiated exon
      trapping from Yp-derived YACs. Sequence analysis of the trapped products has
      identified exons of previously cloned mouse Y-located genes Zfy and SSty and
      potential exons homologous to the human Y-located Tspy gene family. In addition,
      a family of three Yp-located transcripts that show close homology to human RHOA
      (locus designation ARHA), a member of the Ras family of small GTPases, has been
      identified. To determine whether these Yp sequences had been transposed from an
      autosomal ancestor, we used this trapped product to isolate a full-length
      autosomal mouse RhoA cDNA that is 80% identical at the nucleotide level and 98%
      identical at the amino acid level to human RHOA and maps to mouse Chromosome 2
      (locus designation ArhA). Sequence analysis indicates that the Y-linked copies
      have diverged from the autosomal form, with small deletions precluding
      maintenance of a significant open reading frame in all Yp copies. Yet RT-PCR
      analysis indicates that two of these pseudogenes, RhoAy1 and 3, are expressed in
      a testis-specific manner, in sharp contrast to the nearly ubiquitous expression
      pattern of the autosomal ancestor. The data indicate that the Y copies of RhoA
      have been transposed from an autosome, followed by subsequent duplication,
      sequence divergence, and acquisition of a testis-specific promoter/enhancer.

PMID- 9598305
TI  - Genetic mapping of a locus (mass1) causing audiogenic seizures in mice.
AB  - Frings audiogenic seizure-susceptible mice are a model for sensory-evoked reflex
      seizures. Their seizure phenotype is characterized by wild running, loss of
      righting reflex, tonic flexion, and tonic extension in response to high-intensity
      sound stimulation. The Frings mice represent an inbred colony that has not been
      genetically characterized. This investigation studied the mode of inheritance for
      audiogenic seizures by crossing the Frings mouse with the seizure-resistant
      C57BL/6J mouse. Among the backcross progeny generated by crossing (Frings x
      C57BL/6J)F1 mice with the Frings strain, 391 of the 836 N2 progeny were
      audiogenic seizure susceptible, a finding consistent with monogenic inheritance.
      Genetic mapping and linkage analysis of hybrid mice using MIT microsatellite
      marker sequences localized the seizure gene, named mass1 for monogenic audiogenic
      seizure susceptible, to an approximately 3.6 cM interval in the middle of mouse
      chromosome 13. Linkage of mass1 to chromosome 13 is an important step in
      identifying the gene associated with a monogenic seizure disorder in mice, which
      may ultimately lead to a better understanding of the pathophysiology of human
      seizure disorders.

PMID- 9598306
TI  - Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes.
AB  - The NKG2 family of genes (HGMW-approved symbol KLRC) contains at least four
      members (NKG2-A, -C, -E, and -F) which are localized to human chromosome 12p12.3
      p13.2. This region, called the natural killer (NK) complex, encodes for lectin
      like genes preferentially expressed on NK cells. One of them, the human CD94 gene
      (HGMW-approved symbol KLRD1), encodes for a protein that has been shown to be
      covalently associated with the NKG2-A molecule. In this report, we showed that
      the NKG2 and CD94 genes are localized in a small region (< 350 kb) and we mapped
      them in the following order: (NKG2-C/NKG2-A)/NKG2-E/NKG2-F/NKG2-D/CD 94. Sequence
      analysis of 62 kb spanning the NKG2-A, -E, -F, and -D loci allowed the
      identification of two LINE elements that could have been involved in the
      duplication of the NKG2 genes. Presence of one MIR and one L1ME2 element at
      homologous positions in the NKG2-A and NKG2-F genes is consistent with the
      existence of rodent NKG2 gene(s). Finally, we mapped the 5'-ends of the NKG2-A
      transcripts into two separate regions showing the existence of two separate
      transcriptional control regions upstream of the NKG2-A locus and defining
      putative promoter elements for these genes.

PMID- 9598307
TI  - High-resolution YAC fragmentation map of 1q21.
AB  - Chromosomal band 1q21 contains a number of genes, constituting the Epidermal
      differentiation complex (EDC), most of which are involved in the process of
      terminal differentiation of the human epidermis and implicated in several
      disorders of keratinization and cancer. The physical map of 1q21 has been refined
      by generating 400 YAC derivatives. These products have allowed us to localize EDC
      genes and additional ESTs precisely. The transcriptional map of the region has
      been extended by positioning 20 ESTs reported to map between D1S442 and D1S305.
      Eight of the ESTs are localized in two distinct clusters, confirmed by isolating
      PACs and chromosome 1-specific cosmids. Two of the ESTs correspond to the genes
      for YL1 and selenium-binding protein, both of which have potential tumor
      suppressor activity. Through the use of fragmented YACs and bacterial clones, the
      order of markers and ESTs in the region has been established as follows: cen
      A002O32-Bda44g03-Cda10d12-Bdab5d06, H60056, A005K39-D1S442-WI5663-WI7969-Cx40
      Cda0g e12-Cda0kh05-A002D26- A008S07-Cda0ff08-D1S498-S100A10-WI7815( THH)
      WI7217(FLG)-D1S1664-INV-SPRR2A- LOR-A001X21-D1S305-tel.

PMID- 9598308
TI  - High-fidelity digital hybridization screening.
AB  - We developed a highly efficient screening method for minimizing the hybridization
      of high-density replica (HDR) filters and for allowing simultaneous use of
      numerous oligonucleotide probes for STS markers. We designated this method
      "digital hybridization (DH) screening," in which a binary n-bit ID number is
      given to each probe, and a series of probe mixtures is prepared in an arranged
      combination. The matrix pattern between probe mixtures and hybridization signals
      determines the relation between a particular STS marker(s) and the corresponding
      DNA clone(s). Here, we describe a successful DH screening of over 15,000 human
      BAC clones with 126 STS marker probes with 7-bit ID numbers, which required only
      8 sets of HDR filter hybridizations. Our results indicate that DH screening can
      be performed with more than 1000 STS marker probes with only 10-bit ID numbers.
      The DH screening method is convenient, economical, and of high fidelity, and thus
      it should facilitate the construction of sequence-ready DNA contigs for the human
      genome as well as for genomes of various species. The principle of DH screening
      has various applications to the biological sciences.

PMID- 9598309
TI  - Rearrangement of the human CDC5L gene by a t(6;19)(p21;q13.1) in a patient with
      multicystic renal dysplasia.
AB  - Genetic studies have implicated the short arm of chromosome 6 in congenital
      hydronephrosis. In previous studies, we described a fetus carrying a
      t(6;19)(p21;q13.1) as the sole cytogenetic anomaly and suffering from bilateral
      multicystic renal dysplasia caused by a bilateral complete pelviureteric junction
      obstruction, resulting in a massive hydronephrosis. Characterization of the
      chromosome 19 breakpoint region revealed that the transcription factor-encoding
      USF2 gene is affected. In this report, we show that the CDC5L gene on chromosome
      6p is rearranged in the cells of the fetus. CDC5L encodes a protein that is
      related to the product of the Schizosaccharomyces pombe Cdc5 gene, which exerts
      its effects at the G2/M transition during cell cycle progression. We have
      established the genomic organization of the CDC5L gene and found that it consists
      of at least 16 exons spanning approximately 50 kb of chromosome segment 6p21.
      Northern blot analysis indicated that the gene is ubiquitously expressed as a
      single mRNA of about 3.4 kb in both fetal and adult tissues. The translation
      product of the CDC5L gene has an electrophoretic mobility of about 100 kDa and is
      predicted to be a nuclear protein, since it contains a Myb-related DNA binding
      domain and potential nuclear localization signals in its aminoterminal region.
      Immunocytochemical analysis confirmed the nuclear localization of the CDC5L
      protein. CDC5L was also predicted to contain a hydrophilic, proline-rich region
      in its central part, which might function as a transcriptional activating domain.
      The chromosome 6 breakpoint was found in the intron between exons 9 and 10,
      indicating that, as a direct result of the 6;19 translocation, the Myb-related
      DNA binding domains and the nuclear localization signals are separated from the
      putative transactivating domain. Northern blot and RT-PCR experiments revealed
      that the other CDC5L allele is unaffected, and in Western blot experiments,
      expression of the 100-kDa protein was detected in fibroblasts of the fetus.
      Expression of a truncated or hybrid CDC5L transcript resulting from the CDC5L
      rearrangement could not be demonstrated.

PMID- 9598310
TI  - The gene encoding a cationic amino acid transporter (SLC7A4) maps to the region
      deleted in the velocardiofacial syndrome.
AB  - By screening an expressed sequence tag database, we identified a novel human
      gene, SLC7A4, encoding a solute carrier family 7 [cationic amino acid (CAA) CAT-4
      transporter, y+ system] member 4. The SLC7A4 cDNA is 2325 nt long and includes
      78, 1911, and 336 nt in the 5' noncoding, coding, and 3'-noncoding regions,
      respectively. SLC7A4 displays high homology with SLC7A1 and SLC7A2, two
      previously known CAA transporters. By chromosomal in situ hybridization and YAC
      identification, SLC7A4 was mapped to 22q11.2, the commonly deleted region of the
      velocardiofacial syndrome (VCFS, Shprintzen syndrome). In a patient affected by
      VCFS, deletion of SLC7A4 was demonstrated by chromosomal FISH. By Northern
      analysis, an abundant transcript was detected in brain, testis, and placenta.
      Microinjection of SLC7A4 mRNA into Xenopus laevis oocytes demonstrates a
      significant stimulation of CAA transport.

PMID- 9598311
TI  - Detection and isolation of a novel human gene located on Xp11.2-p11.4 that
      escapes X-inactivation using a two-dimensional DNA mapping method.
AB  - Using a two-dimensional DNA mapping method, we detected four NotI restriction
      sites that escape chromosome X-specific methylation in humans. Two genes
      corresponding to two of these sites that lie in the region of Xp11.2-p11.4 were
      cloned and their properties studied. One of the genes matched a known gene, but
      the other, termed EXLM1, is novel and is predominantly expressed in cultured
      lymphocytes and skeletal muscle.

PMID- 9598312
TI  - Hmg4, a new member of the Hmg1/2 gene family.
AB  - High mobility group (HMG) proteins are abundant components of mammalian nuclei
      and fall into three families. The members of one such family, HMG1 and HMG2, are
      ubiquitously expressed and facilitate the formation of nucleoprotein complexes
      where the DNA is sharply bent. We have identified a mouse cDNA that codes for a
      novel 200-amino-acid protein of the HMG1/2 family, which we called HMG4. The
      mouse Hmg4 gene is highly expressed in the embryo; Hmg4 transcripts are barely
      detectable in adult tissues. The human HMG4 gene, which is extremely similar to
      its mouse homolog, has been sequenced as part of chromosome X, band q28. HMG4,
      HMG1, and HMG2 proteins have been highly conserved during vertebrate evolution,
      suggesting that each has at least some unique property. It is possible that HMG4
      is required during development.

PMID- 9598314
TI  - A comprehensive microsatellite linkage map of the chicken genome.
AB  - A comprehensive linkage map of the chicken genome has been developed by
      segregation analysis of 430 microsatellite markers within a cross between two
      extreme broiler lines. The population used to construct the linkage map consists
      of 10 families with a total of 458 F2 individuals. The number of informative
      meioses per marker varied from 100 to 900 with an average of 400. The markers
      were placed into 27 autosomal linkage groups and a Z-chromosome-specific linkage
      group. In addition, 6 markers were unlinked, 1 of which was Z chromosome
      specific. The coverage within linkage groups is 3062 cM. Although, as in other
      species, the genetic map of the heterogametic sex (female) is shorter than the
      genetic map of the homogametic sex (male), the overall difference in length is
      small (1.15%). Forty-five of the markers represent identified genes or ESTs.
      Database homology searches with the anonymous markers resulted in the
      identification of a further 9 genes, bringing the total number of genes/ESTs on
      the current map to 54. The mapping of these genes led to the identification of
      two new regions of conserved synteny between human and chicken and confirmed
      other previously identified regions of conserved synteny between human and
      chicken. The linkage map has 210 markers in common with the linkage maps based on
      the East Lansing and Compton reference populations, and most of the corresponding
      linkage groups in the different maps can be readily aligned.

PMID- 9598313
TI  - Promoter sequence, expression, and fine chromosomal mapping of the human gene
      (MLP) encoding the MARCKS-like protein: identification of neighboring and linked
      polymorphic loci for MLP and MACS and use in the evaluation of human neural tube
      defects.
AB  - The MARCKS-like protein (MLP), also known as F52, MacMARCKS, or MARCKS-related
      protein, is a widely distributed substrate for protein kinase C (PKC). Recent
      studies using gene disruption in vivo have demonstrated the importance of both
      MARCKS and MLP to the development of the central nervous system; specifically,
      mice lacking either protein exhibit a high frequency of neural tube defects. We
      isolated a genomic clone for human MLP and discovered a directly linked
      polymorphism (MLP1) useful for genetic linkage analysis. The MLP promoter was 71%
      identical over 433 bp to that of the corresponding mouse gene, Mlp, with
      conservation of many putative transcription factor-binding sites; it was only 36%
      identical over 433 bp to the promoter of the human gene, MACS, which encodes the
      MLP homologue MARCKS. This 433-bp fragment drove expression of an MLP-beta
      galactosidase transgene in a tissue-specific and developmental expression pattern
      that was similar to that observed for the endogenous gene, as shown by in situ
      hybridization histochemistry. In contrast to MACS, the MLP and Mlp promoters
      contain a TATA box approximately 40 bp 5' of the presumed transcription
      initiation site. MLP was localized to chromosome 1p34-->1pter by analysis of
      human-mouse somatic cell hybrid DNA and to 1p34 by fluorescence in situ
      hybridization. Radiation hybrid mapping of MLP placed it between genetic markers
      D1S511 (LOD > 3.0) and WI9232. MACS was localized to 6q21 between D6S266 (LOD >
      3.0) and AFM268uh5 by the same technique. We tested the novel MLP1 polymorphism
      and the MACS flanking markers in a series of 43 Caucasian simplex families in
      which the affected child had a lumbosacral myelomeningocele. We found no evidence
      of linkage disequilibrium, suggesting that these loci were not major genes for
      spina bifida in these families. Nonetheless, the identification of linked and
      neighboring polymorphisms for MACS and MLP should permit similar genetic studies
      in other groups of patients with neural tube defects and other neurodevelopmental
      abnormalities.

PMID- 9598315
TI  - The human ROX gene: genomic structure and mutation analysis in human breast
      tumors.
AB  - We have recently isolated a human gene, ROX, encoding a new member of the basic
      helix-loop-helix leucine zipper protein family. ROX is capable of
      heterodimerizing with Max and acts as a transcriptional repressor in an E-box
      driven reporter gene system, while it was found to activate transcription in HeLa
      cells. ROX expression levels vary during the cell cycle, being down-regulated in
      proliferating cells. These biological properties of ROX suggest a possible
      involvement of this gene in cell proliferation and differentiation. The ROX gene
      maps to chromosome 17p13.3, a region frequently deleted in human malignancies.
      Here we report the genomic structure of the human ROX gene, which is composed of
      six exons and spans a genomic region of less than 40 kb. In an attempt to
      identify possible inactivating mutations in the ROX gene in human breast cancer,
      we performed a single-strand conformation polymorphism analysis of its coding
      region in 16 sporadic breast carcinomas showing loss of heterozygosity in the
      17p13.3 region. No mutations were found in this analysis. Five nucleotide
      polymorphisms were identified in the ROX gene, three of which caused an amino
      acid substitution. These nucleotide changes were present in the peripheral blood
      DNAs of both the patients and the control individuals. In vitro translated assays
      did not show a significant decrease in the ability of the ROX mutant proteins to
      bind DNA or to repress transcription of a driven reporter gene in HEK293 cells.
      Despite experimental evidence that ROX might act as a tumor suppressor gene, our
      data suggest that mutations in the coding region of ROX are uncommon in human
      breast tumorigenesis.

PMID- 9598316
TI  - Structure and organization of the RBMY genes on the human Y chromosome:
      transposition and amplification of an ancestral autosomal hnRNPG gene.
AB  - The RBMY (RNA-binding motif, Y chromosome) gene family encodes a germ-cell
      specific nuclear protein implicated in spermatogenesis. It consists of
      approximately 30 genes and pseudogenes, found on both arms of the Y chromosome.
      RBMY shares high homology with an autosomal hnRNPG gene that contains an RNA
      binding motif and one of the four SRGY repeats found in RBMY. One proposal is
      that RBMY represents an ancestral hnRNPG gene, transposed to the Y chromosome and
      then amplified. We characterized seven RBMY genes in interval 6 of the Y
      chromosome long arm. Four have the normal structure with 12 exons spanning 15 kb,
      whereas one lacks the first 3 exons, therefore representing a pseudogene. The
      remaining two genes belong to a different subfamily, resembling the autosomal
      hnRNPG gene with only one SRGY repeat. We also found that most RBMY genes in
      interval 6 are arranged in tandem. The structure and organization of the Y-linked
      RBMY genes support the transposition-amplification hypothesis.

PMID- 9598317
TI  - The gene encoding the C gamma catalytic subunit of cAMP-dependent protein kinase
      is a transcribed retroposon.
AB  - Three different catalytic isoforms of cAMP-dependent protein kinase have been
      identified (C alpha, C beta, and C gamma). We report the cloning and
      characterization of the human and rhesus monkey genes encoding the testis
      specific C gamma subunit. The human C gamma gene is intronless with an open
      reading frame similar to the previously published cDNA sequence. The 3' and 5'
      flanking regions share high similarity with the C alpha nontranslated regions
      (82%) also outside the regions corresponding to the C gamma cDNA. The human gene
      is flanked by an Alu-related sequence in the 5'-end and there are insertions of
      two Alu-related sequences in the 3' nontranslated region. The observation that
      the C gamma gene is intronless and colinear with C alpha mRNA, together with the
      presence of remnants of a poly(A) tail and flanking direct repeats, indicates
      that the C gamma gene is a C alpha-derived retroposon. The 5' flanking region of
      this gene has a high G/C content and a putative TATA box situated at -138
      compared to the translation initiation codon. Cloning and sequencing of a partial
      C gamma rhesus monkey gene demonstrate conservation of the sequence in primates.
      Northern analysis on isolated and fractionated human germ cells of testes from
      normal and estrogen-treated individuals demonstrates that the C gamma gene is
      expressed only in germ cells in the human testis. Our results indicate that the C
      gamma gene is a retroposon specifically transcribed in primate testicular germ
      cells.

PMID- 9598318
TI  - Cloning and characterization of 4.1G (EPB41L2), a new member of the skeletal
      protein 4.1 (EPB41) gene family.
AB  - The prototypical erythrocyte membrane skeletal protein 4.1 (HGMW-approved symbol
      EPB41), here designated 4.1R, is encoded by a large, complexly spliced gene
      located on human chromosome 1p32-p33. In this paper we report evidence for a
      second 4.1 gene, 4.1G (HGMW-approved symbol EPB41L2), which maps to human
      chromosome 6q23 and is widely expressed among human tissues. The complete
      nucleotide sequence of 4.1G cDNA predicts a 113-kDa protein that exhibits three
      regions of high homology to 4.1R, including the membrane binding domain, the
      spectrinactin binding domain, and the C-terminal domain. Interspersed among the
      shared domains are unique sequences that may define functional differences
      between 4.1R and 4.1G. Specific isoforms of 4.1R and 4.1G exhibit differential
      subcellular localizations. These results expand the 4.1 gene superfamily and
      demonstrate that the diverse cellular complement of 4.1 isoforms results from
      both alternative splicing and expression of distinct genes.

PMID- 9598319
TI  - Structure and chromosomal localization of a murine LIM/homeobox gene, Lhx8.
AB  - Lhx8 is a LIM-homeodomain protein, containing two tandemly repeated LIM motifs
      and a hemeodomain. The expression of Lhx8 is limited spatially to the medical
      ganglionic eminence and the mesenchyme surrounding the oral cavity and temporally
      from middle embryonic to early postnatal development, suggesting a role for Lhx8
      in differentiation of certain neurons and mesenchymal cells, just as the other
      LIM-homeodomain proteins are implicated in determining the fates of certain cell
      types. Here we report the structure and the chromosomal localization of the Lhx8
      gene. The gene is composed of nine exons and eight introns. The first LIM domain
      is coded by two exons, exons 2 and 3, and the second by a single exon, exon 4.
      The homeodomain is encoded by three exons, exons 6, 7, and 8. In situ chromosomal
      hybridization demonstrated that the Lhx8 gene was localized in the distal region
      of mouse chromosome 3.

PMID- 9598320
TI  - DLG3, the gene encoding human neuroendocrine Dlg (NE-Dlg), is located within the
      1.8-Mb dystonia-parkinsonism region at Xq13.1.
AB  - Neuroendocrine-Dlg (NE-Dlg) is a member of the discs-large-related (DLG)
      subfamily of the membrane-associated guanylate kinase-related protein family.
      Based on evidence from model systems, this protein appears to be critical for
      synaptogenesis, acting as a site-specific organizational center for integral
      membrane proteins and their downstream signaling molecules associated with the
      cytoskeleton. NE-Dlg also directly interacts with the colorectal tumor suppressor
      adenomatous polyposis coli, suggesting that it may play a role in regulating cell
      proliferation in epithelial cells. To explore the genetic control of NE-Dlg, we
      developed a physical map of the chromosome region containing DLG3, the locus
      encoding NE-Dlg. Using human-hamster radiation hybrid mapping panels, we mapped
      DLG3 to Xq13.1 and established a sequence-tagged site marker map of the
      surrounding region. We then developed a yeast artificial chromosome (YAC) contig
      for this region. Encompassing approximately 2.0 Mb contained within five
      overlapping YACs, this contig also includes the dystonia-parkinsonism syndrome
      (DYT3) locus. The close proximity of DLG3 to the DYT3 region suggests that the
      gene encoding NE-Dlg is a candidate locus for this neurological disorder.

PMID- 9598321
TI  - The human TRIP6 gene encodes a LIM domain protein and maps to chromosome 7q22, a
      region associated with tumorigenesis.
AB  - The thyroid receptor interacting protein-6 (TRIP6) was first identified as a
      ligand-dependent binding partner for the thyroid hormone receptor in a yeast two
      hybrid screen. A partial TRIP6 cDNA clone that was isolated in the initial screen
      encodes two copies of the LIM domain. The LIM domain is a double zinc-finger
      structure that mediates protein-protein interactions. Here we report the complete
      amino acid sequence of human TRIP6. The TRIP6 protein displays a proline-rich N
      terminal region linked to three tandemly arrayed C-terminal LIM domains. The
      global molecular architecture and sequence of TRIP6 place it in the same family
      as the adhesion plaque protein, zyxin, and the lipoma preferred partner (LPP).
      Zyxin and LPP are implicated in cellular signaling and tumorigenesis,
      respectively. By radiation hybrid mapping, the human TRIP6 gene was assigned to a
      segment of chromosome 7q22 that is commonly deleted in malignant myeloid diseases
      and uterine leiomyoma.

PMID- 9598322
TI  - A gridded genomic library of the honeybee (Apis mellifera): a reference library
      system for basic and comparative genetic studies of a hymenopteran genome.
AB  - We present a gridded genomic library of the honey-bee (Apis mellifera) for
      comparative and basic genetic study of the honeybee genome. The library will be
      established as a "Reference Library" system, and clones as well as data will be
      shared with the entire scientific community. This will accelerate the molecular
      level of honeybee genetics, combining the efforts of different laboratories.
      Because of male haploidy and the high rate of recombination, the honeybee is
      becoming a model organism for genomic studies of naturally occurring traits and
      behavioral genetics. The library consists of about 110,000 clones spotted at high
      density onto four filter membranes, representing 22 genome equivalents.
      Preliminary analysis using single-copy sequences revealed a positive clone number
      of the same order. The techniques for library generation and preliminary analysis
      as well as library access are described.

PMID- 9598323
TI  - A novel long and unstable CAG/CTG trinucleotide repeat on chromosome 17q.
AB  - Using the direct identification of repeat expansion and cloning technique, we
      cloned a novel long CAG/CTG trinucleotide repeat on chromosome 17. Using
      radiation hybrid panels, the CAG/CTG repeat was mapped to chromosome 17q. The
      CAG/CTG repeat is highly polymorphic, with a heterozygosity of 85%, and exhibits
      a bimodal distribution (allele S, 10-26 repeat units, and allele L, 50-92 repeat
      units). The CAG/CTG repeat of allele L exhibited intergenerational instabilities,
      which are more prominent in maternal transmission than in paternal transmission.
      Analyses of Northern blot and RT-PCR indicate that the repeat is transcribed.
      Although the size of the CAG/CTG repeat of allele L is within the range of the
      expanded CAG repeat of disease-causing genes, we did not detect any association
      of allele L with various neurodegenerative diseases, including frontotemporal
      dementia and parkinsonism, mapped to 17q21-q23.

PMID- 9598324
TI  - Cloning, expression, and chromosomal localization of human long-chain fatty acid
      CoA ligase 4 (FACL4).
AB  - Long-chain fatty acid-CoA ligase (also called fatty acid acyl-CoA synthetase)
      plays an essential role in lipid biosynthesis and fatty acid degradation. We
      report herein the cDNA cloning of the human long-chain fatty acid-CoA ligase 4
      from a brain library. The cDNA encodes a functional long-chain fatty acid-CoA
      ligase that shows preference for arachidonic acid as substrate. We also studied
      the tissue distribution of gene expression by Northern hybridization. Human
      placenta, brain, testis, ovary, spleen, and adrenal cortex have the highest
      levels of expression of the long-chain fatty acid-CoA ligase 4, whereas the GI
      system has the lowest. Finally, this gene was localized to chromosome Xq23 in
      human by FISH analysis.

PMID- 9598325
TI  - Human calumenin gene (CALU): cDNA isolation and chromosomal mapping to 7q32.

PMID- 9598326
TI  - Mapping of the human CD11c (ITGAX) and CD11d (ITGAD) genes demonstrates that they
      are arranged in tandem separated by no more than 11.5 kb.

PMID- 9598327
TI  - Genetic mapping of mouse tumor necrosis factor-alpha converting enzyme (TACE) to
      chromosome 12.

PMID- 9598329
TI  - Assignment of the human CC chemokine MPIF-2/eotaxin-2 (SCYA24) to chromosome
      7q11.23.

PMID- 9598328
TI  - Murine cerberus homologue Cer1 maps to chromosome 4.

PMID- 9598330
TI  - Germ plasm assembly and germ cell migration in Drosophila.
AB  - Many aspects of germ cell behavior, migration, and gonad formation are shared
      between vertebrate and invertebrate species. For example, a specialized germ
      plasm has been observed in many species including Caenorhabditis elegans and
      Xenopus. Furthermore, the fact that Vasa marks germ cells in many species
      suggests that even certain molecular aspects of germ cells may be common between
      different organisms. In most organisms, germ cells initially form at a location
      away from their target mesodermal tissues and have to migrate to reach the
      mesoderm. Further genetic studies will reveal the extent to which molecular
      aspects of germ cell migration and gonad formation are conserved.

PMID- 9598331
TI  - Efficient translation and phosphorylation of Oskar require Oskar protein and the
      RNA helicase Vasa.

PMID- 9598332
TI  - Controls of cell fate and pattern by 3' untranslated regions: the Caenorhabditis
      elegans sperm/oocyte decision.

PMID- 9598333
TI  - The Drosophila germarium: stem cells, germ line cysts, and oocytes.

PMID- 9598334
TI  - Genetic characterization of hadad, a mutant disrupting female gametogenesis in
      Arabidopsis thaliana.

PMID- 9598335
TI  - Establishment of cell type in a primitive organism by cell-specific elimination
      and proteolytic activation of a transcription factor.

PMID- 9598336
TI  - Building organs and organisms: elements of morphogenesis exhibited by budding
      yeast.

PMID- 9598337
TI  - Cortical asymmetries direct the establishment of cell polarity and the plane of
      cell division in the Fucus embryo.
AB  - External gradients, such as unilateral light, applied to apolar zygotes of Fucus
      result in a cortical asymmetry expressed as the actin-dependent translocation of
      existing plasma membrane molecules (e.g., DHP receptors) to the shaded side (Fig.
      1a). This process corresponds to the alignment of the polar axis. The localized
      cortical domain identified by the accumulation of DHP receptors, F-actin, and
      free calcium forms a target site for Golgi vesicle (F granule) secretion.
      Localized secretion of F granules is essential to stabilize the polar axis (Fig.
      1b), and to complete a structural complex at the site for polar growth,
      postulated to span the plasma membrane, from the actin cytoskeleton to the cell
      wall (Fig. 2). Furthermore, targeted secretion of the contents of F granules into
      the plasma membrane and/or cell wall appears to provide localized positional
      information required to orient the first cell division plane and to differentiate
      the rhizoid and thallus cells of the two-celled embryo (Fig. 1c). Our cytological
      approaches using Fucus zygotes point to the importance of directed vesicle
      movement and secretion in creating asymmetries in the plasma membrane/cell wall
      during embryogenesis, which appear to have a critical role in cell morphogenesis.
      Conclusions drawn from these results may provide a useful paradigm for the study
      of cell morphogenesis and pattern formation in higher plant embryos and
      vegetative tissues.

PMID- 9598338
TI  - Asymmetric segregation of the Drosophila numb protein during mitosis: facts and
      speculations.

PMID- 9598339
TI  - On the roles of inscuteable in asymmetric cell divisions in Drosophila.
AB  - Three processes requiring insc, protein localization, RNA localization, and
      mitotic spindle orientation, appear to be tightly correlated but nevertheless
      independent. The apical cortical localization of Insc protein occurs prior to
      mitosis and precedes the basal localization of Pros, Numb, and pros RNA. In insc
      null mutants, neuroblasts divide in more random orientations and fail to
      correctly localize Pros, Numb, and pros RNA to their correct position during
      mitosis. Our results suggest that asymmetric localization of Insc during
      interphase functions to establish positional information for spindle orientation
      and the basal localization of Numb, Pros, and pros RNA during mitosis. Insc
      probably interacts with a number of interacting partners in order to effect its
      various functions. One of its partners, Stau, is involved exclusively in the
      process of RNA localization.

PMID- 9598340
TI  - Maternal genes with localized mRNA and pattern formation of the ascidian embryo.

PMID- 9598341
TI  - Related signaling networks in Drosophila that control dorsoventral patterning in
      the embryo and the immune response.

PMID- 9598342
TI  - Nodal signaling and axis formation in the mouse.

PMID- 9598343
TI  - Axis duplication and anterior identity in the mouse embryo.

PMID- 9598344
TI  - FGF signaling in mouse gastrulation and anteroposterior patterning.

PMID- 9598345
TI  - Lineage and functional analyses of the mouse organizer.

PMID- 9598346
TI  - Goosecoid and goosecoid-related genes in mouse embryogenesis.

PMID- 9598347
TI  - Cell response to different concentrations of a morphogen: activin effects on
      Xenopus animal caps.

PMID- 9598348
TI  - Analysis of Fgf8 gene function in vertebrate development.

PMID- 9598349
TI  - Patterning by genes expressed in Spemann's organizer.

PMID- 9598350
TI  - Brainiac and fringe are similar pioneer proteins that impart specificity to notch
      signaling during Drosophila development.

PMID- 9598351
TI  - Cell culture and whole animal approaches to understanding signaling by Wnt
      proteins in Drosophila.

PMID- 9598352
TI  - Multiple roles of cholesterol in hedgehog protein biogenesis and signaling.

PMID- 9598353
TI  - Control of cell growth and fate by patched genes.

PMID- 9598354
TI  - The smoothened gene and hedgehog signal transduction in Drosophila and vertebrate
      development.

PMID- 9598355
TI  - Wnt5 is required for tail formation in the zebrafish embryo.
AB  - Intercellular signaling molecules, such as those encoded by the Wnt gene family,
      have a fundamental role in various aspects of pattern formation in the developing
      embryo. The zebrafish wnt5 gene encodes a member of a subfamily of Wnt molecules
      thought to be involved in modulating cell behavior during vertebrate development.
      Here, we show that the zebrafish pipetail gene is identical to wnt5. The pipetail
      mutant phenotype is characterized by defects in tail formation and impaired
      maturation of the cells that contribute to cartilaginous elements of the head
      skeleton. This suggests a major role for wnt5 in morphogenetic processes
      underlying tail outgrowth and cartilage differentiation in the head. To
      investigate the function of maternally derived wnt5 mRNA, we generated females
      that were homozygous for pipetail. The lack of a maternal effect phenotype in the
      progeny of these females suggests that no obvious function for the maternal wnt5
      expression can be deduced.

PMID- 9598356
TI  - Genes that control organ form: lessons from bone and branching morphogenesis.

PMID- 9598357
TI  - Branching morphogenesis in the Drosophila tracheal system.

PMID- 9598358
TI  - Branching morphogenesis of the lung: new models for a classical problem.

PMID- 9598359
TI  - The enamel knot: a putative signaling center regulating tooth development.

PMID- 9598360
TI  - BMP signaling and vertebrate limb development.

PMID- 9598361
TI  - Hox genes and mammalian development.

PMID- 9598362
TI  - Intercompartmental signaling and the regulation of vestigial expression at the
      dorsoventral boundary of the developing Drosophila wing.

PMID- 9598363
TI  - The dance of the Hox genes: patterning the anteroposterior body axis of
      Caenorhabditis elegans.

PMID- 9598365
TI  - Cross-regulatory interactions between Hox genes and the control of segmental
      expression in the vertebrate central nervous system.

PMID- 9598364
TI  - The regulation of enhancer-promoter interactions in the Drosophila embryo.

PMID- 9598367
TI  - Upstream and downstream from Brachyury, a gene required for vertebrate mesoderm
      formation.

PMID- 9598366
TI  - Role of the Brn-3 family of POU-domain genes in the development of the
      auditory/vestibular, somatosensory, and visual systems.

PMID- 9598368
TI  - Signal transduction downstream from Ras in Drosophila.

PMID- 9598369
TI  - Mutations that perturb vulval invagination in C. elegans.

PMID- 9598370
TI  - Genetics and the evolution of plant form: an example from maize.

PMID- 9598371
TI  - Control of cell division patterns in developing shoots and flowers of Arabidopsis
      thaliana.

PMID- 9598372
TI  - Pancreas development in the chick embryo.

PMID- 9598373
TI  - The specification of muscle in Drosophila.

PMID- 9598374
TI  - Homeobox genes and heart development.

PMID- 9598375
TI  - A transcriptional pathway for cardiac development.

PMID- 9598376
TI  - Induction of chick cardiac myogenesis by bone morphogenetic proteins.

PMID- 9598377
TI  - Expression of Wnt and Frizzled genes during chick limb bud development.

PMID- 9598378
TI  - Outgrowth and patterning of the vertebrate limb.

PMID- 9598379
TI  - Retrovirus-mediated insertional mutagenesis in zebrafish and identification of a
      molecular marker for embryonic germ cells.

PMID- 9598380
TI  - Graded sonic hedgehog signaling and the specification of cell fate in the ventral
      neural tube.

PMID- 9598381
TI  - Guidance of developing axons by netrin-1 and its receptors.

PMID- 9598382
TI  - The many faces of fasciclin II: Genetic analysis reveals multiple roles for a
      cell adhesion molecule during the generation of neuronal specificity.

PMID- 9598383
TI  - Cell lineage determination and the control of neuronal identity in the neural
      crest.
AB  - The molecular mechanisms underlying the determination of neuronal identity in the
      vertebrate peripheral nervous system are only just beginning to come into focus.
      Many of these mechanisms, such as the involvement of cascades of bHLH
      transcription factors and lateral inhibition via the Notch-Delta system, appear
      to have been conserved from Drosophila (Ghysen et al. 1993; Jan and Jan 1993).
      The way in which these genetic circuits are controlled by instructive growth
      factors, and the manner in which they lead to expression of a particular neuronal
      identity, is far from clear. This process is being elucidated by studies of
      neurogenesis in the peripheral autonomic lineage, which is arguably the best
      understood neurogenic lineage in vertebrates. Emerging evidence is beginning to
      suggest that neuronal diversity within the autonomic and sensory lineages may be
      generated by related, but distinct, mechanisms. All autonomic progenitors express
      a common bHLH protein, MASH1, which appears to be induced by members of the BMP2
      subfamily secreted by the tissues to which these progenitors migrate. Additional
      signals may then act on these progenitors in different locations to induce the
      expression of other transcription factors, which act in conjunction with MASH1 to
      specify the final phenotypes of the different autonomic neuron subtypes
      (sympathetic, parasympathetic, and enteric). Although different classes of
      autonomic neurons develop in very different locations within the body, different
      classes of sensory neurons are located together in dorsal root ganglia. The
      finding that distinct but related subtypes of bHLH proteins, the neurogenins, are
      expressed by different classes of sensory neuron precursors early in development
      suggests that sensory neuron diversity, in contrast to autonomic neuron
      diversity, may be pre-specified at or before the time neural crest cells begin
      their emigration from the neural tube.

PMID- 9598384
TI  - Cadherins in brain patterning and neural network formation.

PMID- 9598385
TI  - Retinoids and posterior neural induction: a reevaluation of Nieuwkoop's two-step
      hypothesis.

PMID- 9598386
TI  - Genetic analysis of pattern formation in the zebrafish neural plate.

PMID- 9598387
TI  - Cell interactions in patterning the mammalian midbrain.

PMID- 9598388
TI  - Otx and Emx functions in patterning of the vertebrate rostral head.

PMID- 9598389
TI  - Summary: a common language.

PMID- 9598390
TI  - Save low-income women and their children first.

PMID- 9598391
TI  - Health care needs of medically underserved women of color: The role of the Bureau
      of Primary Health Care.
AB  - The Bureau of Primary Health Care (BPHC) was developed to increase access to
      comprehensive primary and preventive health care and to improve the health status
      of medically underserved populations. Approximately 43 million Americans fall
      into this category, and the majority are poor, female, young, and uninsured.
      Under the Public Health Services Act, BPHC does not provide direct services, but
      rather assist local communities in identifying populations at risk of poor health
      outcomes and helps these communities through various programs. One of the newest
      initiatives of BPHC is the Office of Minority and Women's Health, developed with
      a mission to help reduce the disparities in the health status of women of racial
      and ethnic minority populations. This article outlines these disparities and
      discusses proposals for reducing them.

PMID- 9598392
TI  - Exploring AIDS-related knowledge, attitudes, and behaviors of female Mexican
      migrant workers.
AB  - AIDS-related knowledge, attitudes, and behaviors were assessed in female Mexican
      migrant laborers. Thirty-two women were administered a modified version of the
      Hispanic Condom Questionnaire. Respondents were knowledgeable about the major
      modes of HIV transmission, but one-third to one-half of the women believed that
      they could contract AIDS from unlikely casual sources. Although respondents
      reported few negative beliefs about condom use, actual condom use with sex
      partners was low and knowledge of proper condom use was problematic.
      Consequently, 75 percent reported never carrying condoms. Implications of these
      findings for future research and provision of services for female Mexican
      migrants are discussed.

PMID- 9598393
TI  - Promoting breast cancer screening in rural, African American communities: the
      "science and art" of community health promotion.
AB  - Implementing community health promotion programs can be a daunting task for
      social workers. Aside from the practical skills necessary for engaging diverse
      groups, it requires an understanding of the complex interplay of several
      theoretical constructs. Using an eight-year breast cancer prevention project, the
      North Carolina Breast Cancer Screening Program, as a case study, this article
      describes both the "science and art" of community health promotion. The article
      provides examples illustrating the "art" of generating participation by both lay
      and professional communities and concludes with guidelines for social workers who
      plan to conduct their own community health promotion programs.

PMID- 9598394
TI  - Asian and Pacific Islander cultural values: considerations for health care
      decision making.
AB  - As the United States becomes more ethnically diverse, health care practitioners
      must learn about the perspectives and values of a variety of cultural groups. Of
      interest is how these cultural values intersect with those of the dominant
      culture, especially in the health care arena. This article explores the values
      that influence decision making among Asian and Pacific Islander cultures, with
      specific illustrations from six of these cultures. The literature, along with our
      observations as health professionals and researchers working in Hawaii, suggest
      potential areas of conflict between the more collectivist values of Asian and
      Pacific Islander cultures and the more individualist orientation of the U.S.
      health care system. Implications for practice and research are presented.

PMID- 9598395
TI  - American Indian perspectives on addiction and recovery.
AB  - The circle of tribal society is "experienced from the inside.... When forced from
      the center, one is "alienated, irritable, and lonely" (Deloria, 1970, p. 13).
      Social workers, as service providers and researchers in collaboration with the
      American Indian women they are privileged to serve, have a distinct opportunity
      for working toward health--the integration of the physical, the emotional, the
      spiritual--in the lives of women who seek help in treatment facilities for
      substance abuse. A genuine contribution to the health of the communities to which
      the women return and to the generations which follow is central to this
      opportunity and lies deep within the circle.

PMID- 9598396
TI  - Income, language, and citizenship status: factors affecting the health care
      access and utilization of Chinese Americans.
AB  - This article reports the results of a randomly administered interview of 1,808
      Chinese American residents of San Francisco. The study examines income, language,
      and citizenship status and their effect on the use of health care services by
      this population. The articles discusses the implications of the findings for low
      income and uninsured individuals, particularly people of immigrant status, and
      concludes with suggestions for local health care planners and advocates.

PMID- 9598397
TI  - The Well: a neighborhood-based health promotion model for black women.

PMID- 9598398
TI  - The sickening implications of globalization.

PMID- 9598399
TI  - Ocular morbidity in leprosy-affected persons.

PMID- 9598400
TI  - Extracapsular cataract extraction and intraocular lens implantation in leprosy
      patients: visual outcome and complications.
AB  - In Belo Horizonte, Brazil, 70 eyes of 53 leprosy patients had extracapsular
      cataract extraction and intraocular lens implantation done during a period of
      four years. The authors analyzed the outcome regarding restoration of vision and
      complications after this procedure. The visual acuity improved in 92.9% of the
      eyes and in 65.7% the acuity had improved by four lines or more on the Snellen
      chart. The post-operative complications could not be associated only to leprosy
      infiltration; in any case, they were not too serious and could be controlled.

PMID- 9598401
TI  - Immunopathology of uveitis.

PMID- 9598402
TI  - Bilateral iridocyclitis caused by Mycobacterium leprae diagnosed through
      paracentesis.
AB  - The authors conducted an anterior chamber paracentesis in a patient with
      lepromatous leprosy showing bilateral iridocyclitis. The paracentesis was
      performed in the outpatients department. The aqueous humor was studied by Ziehl
      Nielsen staining method and the result was the isolation of the M. leprae in the
      anterior chamber. This study shows that M. leprae can promote uveitis in leprosy
      patients. Therefore, it should be looked for in patients having this type of
      disease.

PMID- 9598403
TI  - The epidemiology of ocular complications of leprosy.

PMID- 9598404
TI  - Lagophthalmos in leprosy.

PMID- 9598405
TI  - The prevalence of disabling ocular complications of leprosy: a global study.
AB  - A world-wide study on the ocular complications of leprosy has been carried out
      over the past ten years. The data from 4772 patients, designed to give baseline
      information for a five-year incidence study, have been analysed. Blindness due to
      leprosy was seen in 3.2% of the sample and 7.1% had Grade 2 visual disability.
      The causes of visual impairment in the disease are discussed and it is emphasized
      that a high proportion of these are preventable, particularly through the early
      use of multidrug therapy. The active participation of ophthalmologists in the
      management of the disease is still required since many of the blinding
      complications respond well to surgery.

PMID- 9598406
TI  - Strategies for improvement of management of ocular complications in leprosy.
AB  - Responsibility for eye care of leprosy-affected persons should be shared between
      leprosy and eye care staff. Leprosy and PHC staff should be responsible for:
      treatment of reversal reactions in the face, and of recent lagophthalmos, with
      prednisolone, conservative treatment of mild lagophthalmos, referral of patients
      with severe lagophthalmos and/or exposure keratitis, unless there is sufficient
      expertise within the programme, recognition of the acute red eye and treatment of
      acute conjunctivitis, referral of all other conditions of acute red eye, unless
      there is sufficient expertise within the programme, recognition of severe visual
      impairment and referral as needed, recognition of the need for reading glasses in
      patients aged over 40 years, in rehabilitation services, encouraging medical
      colleges, Control of Blindness Societies, and staff of general eye care
      facilities, to actively take part in the treatment of eye complications in
      patients affected by leprosy, and encouraging charitable organizations to provide
      special eye care programmes for patients affected by leprosy, in particular for
      those who are disabled and are living in leprosy settlements. Eye care services
      (a visiting ophthalmologist or paramedical ophthalmic assistant to the
      specialized leprosy centres for consultation is an appropriate alternative and
      may sometimes be even more feasible) should take the responsibility for: eyelid
      surgery in patients with large lid gaps (> 6 mm), or, signs of exposure
      keratitis, and treatment and follow-up of acute iritis, corneal ulcers, foreign
      bodies, and other causes of 'the acute red eye', in cooperation with the leprosy
      service or PHC staff. The eye care services should offer 'positive
      discrimination' in the treatment of cataract-blind leprosy patients, realizing
      the great difficulties that these patients have in avoiding injuries or taking
      care of injuries once they have occurred, especially in the case of limbs that
      have lost protective sensation.

PMID- 9598407
TI  - The current situation of lagophthalmos and keratopathy of leprosy in PR China.

PMID- 9598408
TI  - Pathology of eye in leprosy.

PMID- 9598410
TI  - Presence of M. leprae in the conjunctiva, vitreous body and retina of a patient
      having lepromatous leprosy.
AB  - Histopathological study of the ocular globe of a lepromatous leprosy patient
      revealed the presence of lepra bacilli in the conjunctiva, sclera, episclera,
      cornea, iris, ciliary body, vitreous body and retina.

PMID- 9598409
TI  - Ocular impairments in an impairment survey of leprosy-affected persons in Nepal.
AB  - An impairment survey was carried out in Nepal. The study subjects (n = 318) were
      a mixture of out-patients and patients admitted less than one month before the
      survey. Of the subjects, 101 were attending the hospital out-patients clinic or
      were admitted and the rest were examined in the field. The patients studied
      included those on MDT and care-after-cure cases. Ocular impairments were found in
      25% of these cases. The most common ocular impairment was poor vision followed by
      lagophthalmos and insensitive cornea.

PMID- 9598411
TI  - Assessment and treatment of the dry eye in leprosy.
AB  - During the period of existence of the Ophthalmologic Prevention Centre we have
      come across a large number of patients with corneal dehydration (dryness cornea,
      dry eye) due to various causes. We find that majority of the patients had a big
      improvement in their symptoms and the signs of the dry eye with just a simple
      prevention technique.

PMID- 9598412
TI  - Longitudinal follow-up of eyes in leprosy.

PMID- 9598413
TI  - Epidemiological aspects of ocular morbidity in leprosy-affected persons.

PMID- 9598414
TI  - Lid surgery to reduce discomfort produces an unexpected improvement in visual
      acuity--a case presentation.
AB  - A significant cause of blindness in leprosy is corneal scarring secondary to
      corneal anaesthesia and lagophthalmos (Brand & ffytche 1985). Such patients may
      continue to experience considerable ocular discomfort, particularly when there is
      associated ectropion of the lower lid, with inflammation of the exposed tarsal
      conjunctiva (Courtright & Johnson 1991). Where visual outcome is no longer the
      primary consideration, one may hesitate to subject patients to surgery,
      particularly in relatively unsophisticated field conditions, attempting instead
      to relieve the patient's discomfort by conservative treatment such as frequent
      topical ocular lubricants, use of protective spectacles or eye shades etc. A case
      is presented here in which minor surgery aimed solely at relieving ocular
      discomfort resulted in an unexpected improvement in visual acuity. This suggests
      that there are instances where a more aggressive approach to treatment of even
      severely damaged eyes could prove more rewarding than anticipated.

PMID- 9598415
TI  - Ocular morbidity in a sample of 150 treated leprosy patients.

PMID- 9598416
TI  - The challenge: organizing services to prevent blindness in leprosy patients.

PMID- 9598418
TI  - Surgical treatment of secondary cataract in leprosy.

PMID- 9598417
TI  - Blindness and low vision in leprosy patients in Sichuan Province, China.
AB  - The acuity of vision of 2145 leprosy patients was examined. Twenty-six patients
      had bilateral blindness and 80 had diminution of vision bilaterally, according to
      WHO's standard. The vision disability rate was 4.94%. In addition, 136 patients
      (6.34%) had blindness or low vision involving one eye. The causes of blindness
      and low vision were leukoma and corneal ulcer.

PMID- 9598419
TI  - Present situation of eye care and research in leprosy in China.

PMID- 9598420
TI  - Estimating treatment effects in clinical crossover trials.
AB  - Some current approaches to modeling crossover trials in two treatments are
      critically reviewed from the perspective of the practical requirements of the
      drug developer. Particular attention is paid to the AB/BA design, and the
      inadequacies of the once popular two-stage procedure are discussed in detail. The
      use of baseline data is also examined. Both frequentist and Bayesian alternatives
      to approaches currently advocated are considered and critically compared. It is
      concluded that it is crucial for the applied statistician working in this field
      to have an appreciation of the practical medical and pharmacological background.

PMID- 9598421
TI  - Crossover designs with correlated observations.
AB  - Crossover designs are widely used in different medical investigations where a
      number of treatments have to be compared. Sequences of treatments are given to
      subjects, and in practice the observations within each subject are likely to be
      correlated. This paper is concerned with the construction of crossover designs
      for such cases. The design problem is nonlinear in the parameters, and design
      optimality depends on the parameters defining the correlation structure. When the
      correlation structure is known, local optimum designs are obtained. When the
      distribution of its parameters is known, optimum Bayesian crossover designs are
      constructed. The optimum sizes of the groups of subjects receiving the same
      sequence of treatments are also determined.

PMID- 9598422
TI  - On the use of the ratio or the odds ratio of cure rates in therapeutic
      equivalence clinical trials with binary endpoints.
AB  - We discuss in this paper some issues related to the use of the ratio or the odds
      ratio of cure rates in therapeutic equivalence clinical trials with binary
      endpoints. Some two one-sided tests procedures are proposed and their fixed
      sample performances evaluated by Monte Carlo simulations. Sample size formulas
      are derived for most of these procedures. The consequences of applying acceptance
      limits proposed for pharmacokinetic responses in bioequivalence studies to
      clinical endpoints in therapeutic equivalence clinical trials are also described.

PMID- 9598423
TI  - Testing simultaneous hypotheses in pharmaceutical trials: a Bayesian approach.
AB  - The purpose of this paper is to compare the Bayes factor and the likelihood ratio
      test in a pharmaceutical trial where the two treatments are a new drug and a
      control (a positive control or a placebo). The goal is to jointly answer the
      questions (1) is the new drug or the control toxic? (2) Is the new drug more
      effective and safer than the control? We consider a bivariate model where each
      treatment is characterized by a target effect (a continuous primary response y)
      and by a side effect (a continuous supplementary response xi). Using a Bayesian
      approach, we account for the uncertainty resulting from prediction of the side
      effect, by making use of the physician's prior inputs about the target-toxicity
      relationship and the maximum tolerated target effects that are considered to be
      safe. Finally, we consider an example about a sleeplessness drug, and we show
      that the Bayes factor provides a more flexible and informative tool than the
      likelihood ratio test in simultaneous testing. Advantages are greater when the
      number of experimental subjects is small.

PMID- 9598424
TI  - A linear model method for rank measures of association from longitudinal studies
      with fixed conditions (visits) for data collection and more than two groups.
AB  - Several statistical methods are available for the analysis of responses with
      ordinal categories or continuous distributions for the respective visits in
      longitudinal studies. This paper discusses an alternative nonparametric strategy
      for studies with more than two groups through Mann-Whitney rank measures of
      association for all pairs of groups. The proposed method is based on U-statistic
      theory, and it applies a linear or linear logistic model to the Mann-Whitney
      estimators for the probabilities of better response for each group relative to
      each of the others. In addition, the ways of adjusting for covariables and
      managing stratification factors are explained. Analysis of parallel dose-response
      relationships for two treatments is illustrated for the proposed method with data
      from a multicenter study with repeated measurements. A nonparametric estimator
      for relative potency is provided from the method.

PMID- 9598425
TI  - An extension of Satterthwaite's approximation applied to pharmacokinetics.
AB  - Satterthwaite's approximation for the degrees of freedom of a linear combination
      of independent mean squares is extended to the case that the mean squares are
      correlated. The mean squares are sample variances where some of the experimental
      units have been used in more than one sample. The motivation for such an
      extension comes from pharmacokinetics. The observations, taken at different time
      points from a set of animals, are blood drug concentrations. Some animals were
      sampled at more than one time point. A linear combination of sample means
      provides an estimate of the population mean area under the concentration-versus
      time curve, which is an indicator of drug exposure. An associated linear
      combination of sample variances provides an estimate of the variance of the area
      estimator. The behavior of confidence intervals based on the approximation was
      studied by simulation. The confidence interval for the population mean,
      constructed by assuming that the variance estimator has a chi-square distribution
      with the computed degrees of freedom, achieved close to its nominal 95% coverage,
      justifying the extension of Satterthwaite's approximation.

PMID- 9598426
TI  - On the singularity of the covariance matrix for estimates of multinomial
      proportions.
AB  - It is well known that the covariance matrix for the multinomial distribution is
      singular and, therefore, does not have a unique inverse. If, however, any row and
      corresponding column are removed, the reduced matrix is nonsingular and the
      unique inverse has a closed form. We elucidate some of the properties of the
      multinomial covariance matrix and its reduced forms. We state and prove a theorem
      that gives insight into the singularity and its removal. Based on these results,
      we establish that the covariance matrix for the multinomial distribution is
      positive semidefinite and that the reduced matrix is positive definite. In
      addition, we show that the determinant of the reduced matrix is invariant to the
      particular row and column that are removed. Goodness-of-fit statistics, including
      Pearson's chi-square, and justification of the degrees of freedom follow from the
      multivariate central limit theorem once the singularity is removed.

PMID- 9598427
TI  - Power considerations when a continuous outcome variable is dichotomized.
AB  - An investigator can compare two groups with respect to a continuous outcome
      variable, Y, by comparing the means of Y or by collapsing that variable into
      categories. For example, antihypertensive treatments can be compared on the basis
      of blood pressure measurements, or on the basis of the proportions of patients
      with blood pressure in prespecified ranges. This report is concerned with the
      loss of power when inherently continuous variables are dichotomized. The report
      will focus on the power loss when a normally distributed variable with a known,
      common variance in each of two groups is dichotomized. Power is shown to depend
      on the relationship between the means of the two groups and the cutoff point, and
      it varies from negligible to substantial. The results will be applied to data
      from the Lovastatin Restenosis Trial. Initially the trial considered a
      dichotomous outcome (proportion of patients with elevated percent diameter
      stenosis), but the endpoint was later changed to the mean percent diameter
      stenosis. The modification in the design of the trial was well justified because
      the power loss was considerable when comparing proportions.

PMID- 9598428
TI  - Caring for patients with dementia: an indication for "emotional communism".

PMID- 9598429
TI  - Ethics and Alzheimer's disease: widening the lens.

PMID- 9598430
TI  - Toward a theory of dementia care: ethics and interaction.

PMID- 9598431
TI  - Voices of Alzheimer's disease sufferers: a call for treatment based on
      personhood.

PMID- 9598432
TI  - Living with Alzheimer's disease: the creation of meaning among persons with
      dementia.

PMID- 9598433
TI  - Reasons and feelings, duty and dementia.

PMID- 9598434
TI  - Persons with dementia as "liability magnets": ethical implications.

PMID- 9598435
TI  - The fear of forgetfulness: a grassroots approach to an ethics of Alzheimer's
      disease.

PMID- 9598436
TI  - Personhood, spirituality, and hope in the care of human beings with dementia.

PMID- 9598437
TI  - Malaria risk factors in an endemic region of Sri Lanka, and the impact and cost
      implications of risk factor-based interventions.
AB  - In an 18-month study of malaria in a population of 1,875 residents in 423 houses
      in an endemic area in southern Sri Lanka, the risk of malaria was found to be 2.5
      fold higher in residents of poorly constructed houses than in those living in
      houses of good construction type. In residents of poorly constructed houses but
      not in others, the risk was even greater when the house was located near a source
      of water that could act as a potential breeding place for malaria vector
      mosquitoes (P = 0.0001). Based on previous findings that confirmed that house
      construction type was itself a risk determinant, and not merely a marker of other
      behavioral factors, we have estimated the potential impact of two feasible
      interventions to reduce the risk of malaria: 1) the imposition of a buffer zone
      of 200 meters around bodies of water from which houses of poor construction were
      excluded, which was estimated to lead to a 21% reduction of the malaria incidence
      in the overall population and a 43% reduction in the relocated community; and 2)
      the conversion of houses of poor construction type located in the buffer zone to
      those of a good construction type, which was estimated to lead to a 36% reduction
      in the incidence rates in the whole population and a 76% reduction in the
      residents of houses whose construction type was improved. Taking into
      consideration the cost to the Government of malaria prevention, we estimated the
      worth of a Government's investment in improving house construction type. The
      investment in housing was estimated to be offset in 7.2 years by savings to the
      Government on malaria costs alone, and beyond this period, to bring a return on
      the Government's investment by way of savings to the malaria control program.

PMID- 9598438
TI  - Use of monoclonal antibodies prepared against Schistosoma mansoni hatching fluid
      antigens for demonstration of Schistosoma haematobium circulating egg antigens in
      urine.
AB  - A panel of 17 monoclonal antibodies (MAbs) against Schistosoma soluble egg
      antigens (SEAs) was produced from BALB/c mice immunized with antigens
      secreted/excreted by Schistosoma mansoni eggs. In this study, we demonstrate that
      16 MAbs were reactive with S. haematobium SEA in addition to S. mansoni SEA. The
      MAbs were tested as potential immunodiagnostic reagents in a homologous sandwich
      ELISA format to detect circulating soluble egg antigens (CSEAs) in serum and
      urine samples of S. mansoni- or S. haematobium-infected individuals. When samples
      of S. mansoni-infected individuals were tested, none of these MAbs performed as
      good as the previously described S. mansoni-specific 114-5B1-A and 114-4D12-A
      MAbs. However, 11 MAbs (of the IgM isotype) detected CSEA in urine samples of S.
      haematobium-infected individuals. Three MAbs, 290-2E6-A, 291-3D5-A, and 291-5D5
      A, were selected for a pilot study with 47 urine samples of S. haematobium
      infected individuals from Kenya. The CSEA levels detected with each of these
      ELISAs showed a significant correlation with urinary egg counts (Spearman rho >
      0.37, P < 0.01) and with each other (Spearman rho > 0.74, P < 0.001). Based on
      the 92% specificity and 90% sensitivity of the assay, the ELISA using MAb 290-2E6
      A was found to be the most promising assay for immunodiagnosis of S. haematobium
      infections.

PMID- 9598439
TI  - Rapid diagnosis of Indian visceral leishmaniasis using achatininH, a 9-O
      acetylated sialic acid binding lectin.
AB  - We have developed a rapid, accurate, and inexpensive hemagglutination assay (HA)
      for diagnosis of Indian visceral leishmaniasis (VL) using achatininH, a 9-O
      acetylated sialic acid binding lectin. The assay is based on the selective
      binding of achatininH to 9-O-acetylated derivatives of sialic acid (9-O-AcSA),
      which appears exclusively on the erythrocytes of patients with VL. Blood samples
      from 35 patients with demonstrable splenic or bone marrow amastigotes were
      assayed by HA and compared with an ELISA. All cases were correctly diagnosed by
      HA, and were in concordance with the ELISA. The increase in 9-O-AcSA was
      corroborated by direct fluorimetric estimation of sialic acid and its 9-O
      acetylated derivative. Therefore, 9-O-acetylated derivatives of sialic acid,
      absent in normal erythrocytes, serve as an important biomarker, and indirectly
      reflect the presence of the parasite. Accordingly, this assay can be used for
      detection of active kala-azar cases and merits clinical consideration.

PMID- 9598440
TI  - Modification of the clinical course of intestinal microsporidiosis in acquired
      immunodeficiency syndrome patients by immune status and anti-human
      immunodeficiency virus therapy.
AB  - The clinical course of 37 Enterocytozoon bieneusi-infected acquired
      immunodeficiency syndrome patients with diarrhea was studied. Parasite clearance
      was seen in 15 patients (40.5%). Clearance of E. bieneusi resulted in a 25-100%
      reduction in episodes of diarrhea, suggesting that microsporidia are true
      pathogens. Univariate and multivariate proportional hazards analyses revealed
      that peripheral blood CD4 cell counts > or = 100/mm3, the use of two or more
      antiretroviral medications, and use of a protease inhibitor were statistically
      associated with decreased time to clearance of E. bieneusi. Specific anti
      microsporidial therapy (albendazole) was not associated with parasite
      eradication. Factors related to immunocompetence and human immunodeficiency virus
      suppression appeared to be important in the clearance of E. bieneusi.

PMID- 9598441
TI  - Examination of the prevalence and seasonal variation of intestinal
      microsporidiosis in the stools of persons with chronic diarrhea and human
      immunodeficiency virus infection.
AB  - The epidemiology of human microsporidiosis is poorly understood and environmental
      factors affecting transmission of the organism have not been fully elucidated.
      Temporal variation in the prevalence of microsporidia in the stool of patients
      with human immunodeficiency virus (HIV) infection and diarrhea was studied to
      evaluate the role of water-borne transmission. From January 1993 to December
      1996, 8,439 stools from HIV-infected individuals were examined for microsporidia
      spores in southern California. Yearly positivity rates were 8.8% in 1993, 9.7% in
      1994, 6.6% in 1995, and 2.9% in 1996. An analysis for linear trend showed a
      statistically significant decrease in stool positivity rates over time (chi2 =
      81.9, P = 0.001). No significant seasonal variation in the prevalence of
      microsporidiosis was seen over that time period. These results suggest the
      constant presence of microsporidia in the environment, rather than a seasonal
      association with recreational water use or seasonal contamination of the water
      supply, and a real decrease in yearly prevalence of microsporidia related
      diarrhea. Factors related to a progressive decrease in prevalence are subjects of
      future investigation.

PMID- 9598442
TI  - Estimation of vector infectivity rates for plague by means of a standard curve
      based competitive polymerase chain reaction method to quantify Yersinia pestis in
      fleas.
AB  - The prevalence of infectivity within a vector population is a critical factor in
      arthropod-borne disease epidemiology but it is difficult to estimate. In the case
      of bubonic plague, infective flea vectors contain large numbers of Yersinia
      pestis within a bacterial mass that blocks the flea's foregut, and only such
      blocked fleas are important for biologic transmission. A bacterial quantitation
      method could therefore be used to assess the prevalence of plague-infective
      (blocked) fleas in a population. We developed a standard, curve-based,
      competitive polymerase chain reaction (PCR) procedure to quantitate Y. pestis in
      individual fleas. The quantitative PCR (Q-PCR) method equaled a colony count
      reference method in accuracy and precision when evaluated using mock samples and
      laboratory-infected fleas. The Q-PCR was more reliable than colony count,
      however, for field-collected fleas and for blocked fleas collected after their
      death. In a sample of fleas collected from a prairie dog colony in the aftermath
      of a plague epizootic, 48% were infected but less than 2% contained numbers of Y.
      pestis indicative of blockage. The method provides a means to monitor plague
      epizootics and associated risks of flea-borne transmission to humans, and is
      applicable to the study of other vector-borne diseases.

PMID- 9598443
TI  - Genotypic identification of an undescribed spotted fever group rickettsia in
      Ixodes ricinus from southwestern Spain.
AB  - An undescribed rickettsia was directly analyzed with specific rickettsial
      molecular biology tools on Ixodes ricinus L. collected in different localities of
      the province of Cadiz (southwestern Spain). On the basis of the results of the
      citrate synthase (glta) gene, 190 kD-outer membrane protein (rOmpA) gene, and 16S
      ribosomal RNA (16S rRNA) gene partial sequence data, it was found that this
      rickettsia is sufficiently genetically distinct from other Rickettsia to be
      considered a distinct taxonomic entity. The isolation and culture of this
      organism, as well as comparative antigenic analysis, are required to ensure its
      conclusive taxonomic placement among spotted fever rickettsiae. The epidemiologic
      role of this new rickettsial agent and its possible pathogenicity to wild and
      domestic animals or humans is still unknown and needs to be investigated.

PMID- 9598444
TI  - Monitoring of dengue viruses in field-caught Aedes aegypti and Aedes albopictus
      mosquitoes by a type-specific polymerase chain reaction and cycle sequencing.
AB  - Virologic surveillance for dengue through the detection of the prevalent
      serotype(s) circulating in the human population during inter- and intra-epidemic
      periods constitutes a reliable sentinel system for dengue outbreaks. We have
      applied a rapid and sensitive, semi-nested, reverse transcription-polymerase
      chain reaction (RT-PCR) assay using nonstructural protein 3 gene primers for the
      type-specific-detection of dengue viruses in artificially infected and in field
      caught adult Aedes mosquitoes. In laboratory experiments, the assay was sensitive
      enough to detect one virus-infected mosquito head in pools of up to 59 uninfected
      heads. In a prospective field study conducted from April 1995 to July 1996,
      female adult Ae. aegypti and Ae. albopictus mosquitoes were caught from selected
      dengue-sensitive areas in Singapore and assayed by RT-PCR. Approximately 20% of
      309 mosquito pools were positive for dengue viruses. Of the 23 RT-PCR-positive
      Ae. aegypti pools (containing 1-17 mosquitoes each), 18 pools (78.3%) were
      positive for dengue 1 virus. There were 40 RT-PCR-positive Ae. albopictus pools
      (containing 1-33 mosquitoes each) of which 31 (77.5%) were positive for dengue 1
      virus. The predominant virus type responsible for the current dengue epidemic
      since 1995 was also dengue 1. The geographic locations of the virus-infected
      mosquitoes correlated with the residences or workplaces of patients within dengue
      outbreak areas. A total of 43.5% of the positive Ae. aegypti pools and 25.0% of
      the positive Ae. albopictus pools contained only a single mosquito. Both Aedes
      species showed similar overall minimum infection rates of 57.6 and 50 per 1,000
      mosquitoes. Infected Ae. aegypti were detected as early as six weeks before the
      start of the dengue outbreaks in 1995 and 1996. However, infected Ae. albopictus
      appeared later, when the number of cases was increasing. Virologic surveillance
      by RT-PCR for detecting dengue virus-infected Aedes mosquitoes in the field may
      serve as an early warning monitoring system for dengue outbreaks.

PMID- 9598445
TI  - Short report: Diapause, transovarial transmission, and filial infection rates in
      geographic strains of La Crosse virus-infected Aedes triseriatus.
AB  - La Crosse (LAC) virus is transmitted horizontally to vertebrates and vertically
      to progeny by Aedes triseriatus mosquitoes, and in northern midwestern states,
      this virus overwinters in diapausing eggs of the vector. In Florida, the vector
      remains active throughout the year and does not diapause. To determine if there
      is an association between diapause and vertical transmission efficiency of LAC
      virus, transovarial transmission (TOT), and filial infection (FI) rates were
      determined for geographic strains of Ae. triseriatus. The TOT rates were not
      significantly different for Ae. triseriatus originating from Florida (78%) and
      those from Wisconsin (85%). The FI rates did differ significantly between the two
      groups (33% and 45%, respectively, for the Florida and Wisconsin mosquitoes).
      Furthermore, a line of mosquitoes was selected from a Wisconsin colony that had a
      reduced diapause phenotype (the AD- strain). While this strain displayed TOT
      rates that were the same as the other Wisconsin mosquitoes (85%), the FI rates
      were significantly lower (34%), indicating a reduction in TOT efficiency. The
      role of vertical transmission capacity in LAC virus endemicity remains to be
      determined.

PMID- 9598446
TI  - Epidemiologic characterization of American cutaneous leishmaniasis in an endemic
      region of eastern Venezuela.
AB  - The status of American cutaneous leishmaniasis was investigated from 1985 to 1991
      to provide an epidemiologic characterization of the disease in Bergantin, a rural
      community in the northeastern part of Anzoategui State, Venezuela. The study
      revealed the presence of the infection during the period analyzed, with an
      average incidence of 50.2 cases per 10,000 inhabitants and this number has
      increased 1.5 times during the last two years. Three villages where clinical
      cases had been recorded were selected for a comparison of their prevalence data.
      These villages comprise the human population in the high and low altitude limits
      of Bergantin. Immunologic assessment of the inhabitants used two different
      antigen preparations to examine responses to parasites associated with the
      cutaneous and visceral forms of the disease. The leishmanin skin test (LST) was
      used in a sample of 276 individuals (46.3% of the inhabitants) and resulted in an
      overall positivity of 16.7%. The percentage of LST positivity varied with age and
      sex, yet analysis of this response and the prevalence for each village reflected
      the specific characteristics of these localities. La Montana, situated at 800
      meters above sea level, had the highest prevalence (800 cases per 10,000
      inhabitants) and the most positive LST response (21.2%) in comparison with the
      two other villages situated at a lower altitude (300 meters above sea level).

PMID- 9598447
TI  - Current status of onchocerciasis in Colombia.
AB  - To assess the current epidemiologic status of onchocerciasis in Colombia two
      surveys were undertaken in 1995 in a suspected new focus on the border between
      Colombia and Ecuador and in the known focus located on the Micay River. No new
      focus was found along the Colombia-Ecuador border. In the known focus,
      communities along the upper Micay River and its tributaries were surveyed; 655
      adults underwent physical examinations and skin biopsies. Infected individuals
      were found almost exclusively in the community of Naiciona, where prevalence of
      infection was 40% (36 of 91). Polymerase chain reaction detection of onchocercal
      DNA in skin snips correlated with the skin-snip biopsy results. The prevalence of
      punctate keratitis, the only ocular manifestation found, was 33%. A rapid
      entomologic assessment demonstrated Simulium exiguum infected with Onchocerca
      volvulus. This is the first finding in Colombia of naturally infected black flies
      and confirms S. exiguum as a vector species. These data will be used for
      implementing a control program using periodic ivermectin distribution.

PMID- 9598448
TI  - Risk factors associated with human cystic echinococcosis in Florida, Uruguay:
      results of a mass screening study using ultrasound and serology.
AB  - Sonographic evidence of asymptomatic Echinococcus granulosus lesions in the liver
      was found in 156 of 9,515 persons in the Department of Florida, Uruguay. The
      sensitivity of ELISA and latex agglutination serology compared with ultrasound
      was 47.6% and 28.1%, respectively, and specificity was > 85%. There was a
      significant positive association between positive sonography and a personal
      history of previous but treated Echinococcus infection while those that were
      seropositive but ultrasound-negative were significantly more likely to have a
      personal history of infection or a history of infection in their family.
      Prevalence of infection increased significantly with age. There was no
      correlation between echinococcosis and dog ownership or home slaughter of sheep
      but offal disposal was important, with an increased prevalence of infection of
      3.2%, 2.8%, and 3.1%, respectively, in persons feeding offal to dogs or burying
      or burning it compared with a prevalence of 0.8-1.5% in those using other methods
      of disposal. Almost half the population, when questioned, seemed to have sound
      knowledge about E. granulosus and described correct treatment of E. granulosus in
      dogs but this did not affect prevalence. There was a significant positive
      association between infection and the presence of a fenced fruit/vegetable garden
      and use of rural waters, particularly the cachimba (a small dam) and the aljibe
      (a cistern or tank) that collect rainwater from the ground surface and roofs,
      respectively.

PMID- 9598449
TI  - Prevalence of and risk factors for anemia in young children in southern Cameroon.
AB  - Anemia during childhood remains a major public health challenge in sub-Saharan
      Africa. To determine the prevalence of and the main risk factors for anemia in
      young children, we conducted a longitudinal survey in Ebolowa in southern
      Cameroon. Children were enrolled in two cohorts and followed during a three-year
      period: the first cohort was composed of 122 children from 0 to 36 months of age
      and the second cohort was composed of 84 children from 24 to 60 months of age.
      The two cohorts were followed weekly for symptomatic malaria, monthly for both
      symptomatic and asymptomatic malaria, and every six months for hematologic data;
      the children were grouped into six-month age groups. The prevalence of anemia
      (hemoglobin [Hb] level < 11 g/dl) was the highest in the six-month-old age group
      (47%) and the age-related evolution clearly showed a decrease in the prevalence
      from three years of age. Thus, 42% of the children less than three years of age
      were anemic, while 21% of the children between three and five years of age were
      anemic. The lowest mean +/- SD Hb content (10.7 +/- 2.1 g/dl) was observed in the
      six-month-old children and a regular improvement in the Hb level occurred from
      six months to three years of age. A stabilization was observed at a level of
      approximately 12 g/dl. At any age, there was no difference in mean Hb levels
      between children with AS and AA Hb genotypes. Hookworm infection was diagnosed in
      two children in the study population. Results of a multivariate analysis showed
      that placental malaria infection was the strongest risk factor for anemia in the
      six-month-old children (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 1.1
      12.3) and was independent of the frequency of parasitemia, parasitemia at the
      time of Hb measurement, or microcytosis. In the one-year-old age group,
      microcytosis was a significant factor related to anemia (OR = 2.8, 95% CI = 1
      7.8) pointing out the role of iron deficiency at this age. Parasitemia at the
      time of Hb measurement was significantly associated with anemia in all age groups
      (except in 54- and 60-month-old groups). Strategies to decrease the prevalence of
      anemia in young children in southern Cameroon should include chemoprophylaxis for
      pregnant women, prevention of acquired malaria infection in both pregnancy and
      infancy, and prevention of nutritional iron deficiency.

PMID- 9598450
TI  - Follow-up of the susceptibility of Plasmodium falciparum to antimalarials in
      Gabon.
AB  - The sensitivity of Plasmodium falciparum to chloroquine, mefloquine, quinine,
      quinidine, halofantrine, artemisinin, and sulfadoxine/pyrimethamine was
      investigated in Lambarene, Gabon in 1994. The development of in vitro
      susceptibility has been traced from 1983 or 1992 to 1994 for chloroquine,
      mefloquine, halofantrine, and quinine. Standard in vitro microtests according to
      World Health Organization methodology were performed. Of 33 isolates tested for
      susceptibility to chloroquine, 31 were resistant, one was borderline, and one
      isolate was sensitive (mean 50% effective concentration [EC50] = 1.38 micromol/L
      of blood). With mefloquine, all isolates were fully inhibited below the threshold
      of resistance (mean EC50 = 0.51 micrmol/L of blood). Of 32 isolates tested with
      quinine, six had borderline resistance (mean EC50 = 0.54 micromol/L of blood
      medium mixture). Susceptibility to quinidine was higher with a mean EC50 of 0.15
      micromol/L of blood medium mixture. With halofantrine, 26 of 32 isolates matured
      at 3 nmol/L of blood medium mixture (mean EC50 = 1.64 nmol/L of blood medium
      mixture), indicating a steep decrease in susceptibility in comparison with 1992.
      For artemisinin, the mean EC50 was 97.92 nmol/L of blood medium mixture.
      Sulfadoxine/pyrimethamine showed five of 16 resistant isolates with a mean EC50
      of 2.46 nmol/L of blood medium mixture. Whereas chloroquine resistance remained
      stable with a tendency to decrease, susceptibility to mefloquine and quinine was
      slightly decreased. A significant increase in the mean EC50 and EC90 in
      comparison with our previous data from Gabon was found for halofantrine.

PMID- 9598451
TI  - Malaria chemotherapy trial at a minimal effective dose of
      mefloquine/sulfadoxine/pyrimethamine compared with equivalent doses of
      sulfadoxine/pyrimethamine or mefloquine alone.
AB  - In murine malaria the addition of mefloquine to sulfadoxine/pyrimethamine has
      been shown to exert an additive effect and to significantly slow the emergence of
      resistance to the individual components. In a pilot study carried out in Gabon, a
      reduced dosage of the triple combination with a mean of 1 mg/kg of mefloquine/2
      mg/kg of sulfadoxine/0.1 mg/kg of pyrimethamine (Fansimef; Roche, Basel,
      Switzerland) had previously been shown to achieve high cure rates in Plasmodium
      falciparum malaria. To evaluate the additive effect, a randomized, double-blind
      trial in school children with mild P. falciparum malaria was performed in Gabon.
      Two hundred thirty-one patients evaluated received a single dose of either the
      triple combination with a mean of 1.07 mg/kg of mefloquine/2.14 mg/kg of
      sulfadoxine/0.11 mg/kg of pyrimethamine (group MSP), or 1.07 mg/kg of mefloquine
      alone (group M), or 2.14 mg/kg of sulfadoxine/0.11 mg/kg of pyrimethamine alone
      (group SP). In the MSP group and the SP group, 67% and 69% of the patients were
      parasitologically cured, respectively, compared with only 13% in the M group (P <
      0.001). A significantly higher parasitemia was found in the M group compared with
      the MSP group or the SP group on days 2 and 3 after the start of treatment. The
      high efficacy of the low dose sulfadoxine/pyrimethamine regimen was the most
      surprising finding of this study.

PMID- 9598452
TI  - In vitro and in vivo reversal of chloroquine resistance in Plasmodium falciparum
      with promethazine.
AB  - The effect of combining promethazine with chloroquine was examined against
      Plasmodium falciparum in vitro in the Aotus-P. falciparum model and in bioassays
      from volunteers given promethazine. The combination of chloroquine plus
      promethazine (1 x 10(-6) M) reversed chloroquine resistance in standard P.
      falciparum clones and patient parasite isolates from Nigeria. The combination
      reduced the 50% inhibitory concentrations (IC50s) for chloroquine against
      resistant parasites by 32-92%. Coadministration of promethazine with chloroquine
      also demonstrated a dose-dependent effect in Aotus monkeys infected with
      chloroquine-resistant P. falciparum. Monkeys were given a chloroquine dose (20
      mg/kg of body weight for seven days), which normally has no effect on
      parasitemia, plus 10, 20, 40, or 80 mg of promethazine/kg of body weight. In one
      monkey, parasitemia was suppressed at the lowest promethazine dose, but re
      treatment with 20 mg/kg resulted in clearance of parasitemia. Initial treatment
      with chloroquine and 20 or 40 mg/kg of promethazine cleared parasitemia in some
      animals followed by recrudescence. Re-treatment at higher doses cured one monkey
      and resulted in initial clearance and delayed recrudescence 28 or 63 days after
      treatment in two monkeys. Recrudescent parasitemia in the two monkeys was low (10
      parasites/microl of blood) and subsequently cleared without re-treatment. An in
      vitro bioassay model was developed to examine the effects of clinically
      achievable doses of promethazine on parasites susceptibilities in vitro. Plasma
      samples taken at hourly intervals from patients given a single oral dose of 25 mg
      of promethazine decreased the IC50 values for chloroquine by 20-58% with the most
      significant reductions occurring in plasma obtained from volunteers 3-4 hr after
      ingestion. Plasma obtained from two volunteers 6 hr after ingestion of the drug
      demonstrated no effect on chloroquine susceptibility, suggesting that study of
      the pharmacokinetic disposition and potential interaction is warranted to
      optimize the dose regimen in patients for antimalarial efficacy. Historic use of
      this drug combination for treatment or prevention of chloroquine-associated
      pruritus or as an antiemetic suggest that the combination is safe and effective
      when used at standard dosages. The results from this study demonstrate that
      promethazine is a potent modulator of chloroquine resistance. Clinical evaluation
      of therapeutic regimens is required to validate clinical efficacy of this
      promising combination for treatment of uncomplicated chloroquine-resistant
      malaria.

PMID- 9598453
TI  - Characterization of Plasmodium falciparum isolated from the Amazon region of
      Brazil: evidence for quinine resistance.
AB  - The prevalence and severity of drug-resistant malaria is emerging rapidly in the
      Amazon basin of Brazil. In support of clinical trials using the new antimalarial
      drug combination of atovaquone and proguanil, we performed in vitro drug
      sensitivities, molecular characterization of parasite populations using the
      circumsporozoite protein, merozoite surface antigen-1 (MSA-1), and MSA-2 markers,
      and an analysis of the Plasmodium falciparum multidrug resistance (pfmdr1) gene
      sequence and copy number in 26 isolates of P. falciparum obtained in a gold
      mining endemic area in Peixoto de Azevedo, Mato Grosso State. All 26 isolates
      were found to be resistant to chloroquine (50% inhibitory concentration [IC50] =
      100-620 nM) and sensitive to mefloquine (IC50 < 23 nM) and halofantrine (IC50 < 6
      nM). The isolates also show reduced susceptibility to quinine (IC50 = 48-280 nM).
      Sequence analysis of the pfmdr1 gene revealed Asn, Phe, Cys, Asp, and Tyr in
      positions 86, 184, 1034, 1042, and 1246, respectively. These point mutations were
      similar to that previously described in other Brazilian isolates. Southern blot
      analysis revealed no amplification of the pfmdr1 gene. These results suggest that
      three different mechanisms for drug resistance exist for chloroquine, mefloquine,
      and quinine.

PMID- 9598454
TI  - A randomized controlled trial of artemether/benflumetol, a new antimalarial and
      pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in
      African children.
AB  - We report here the results of a randomized double blind trial comparing
      coartemether (CGP56697), a combination of artemether and benflumetol, with
      pyrimethamine/sulfadoxine (P/S). Two hundred eighty-seven children 1-5 years of
      age with uncomplicated falciparum malaria were enrolled at two centers in The
      Gambia between July 1996 and December 1996. Following treatment, children were
      visited at home every 24 hr until a blood film free of asexual parasites was
      obtained. Genotyping of parasites was used to distinguish recrudescence from new
      infections. Three days after the start of treatment, 133 (100%) of the CGP56697
      treated children compared with 128 (93.4%) of children treated with P/S had
      cleared their parasites (P = 0.003). The day 15 cure rate was 93.3% for CGP56697
      and 97.7% for P/S (P = 0.13). Within the third and fourth week after initiation
      of therapy, 20 children treated with CGP56697 and one of the P/S-treated children
      returned with second malaria episodes (P < 0.0001). Genotyping suggested that the
      majority (19 of 23 [82.6%]) of these second episodes were due to new infections,
      supporting the World Health Organization recommendation that longer follow-up is
      not relevant for the assessment of drug efficacy. At the two-week follow-up,
      28.9% of the P/S treated children but none of the CGP56697-treated children
      carried gametocytes (P < 0.0001). This study showed that CGP56697 is safe in
      African children with acute uncomplicated falciparum malaria, clears parasites
      more rapidly than P/S, and results in fewer gametocyte carriers. More frequent
      new infections within the third and fourth week following treatment with CGP56697
      than treatment with P/S are likely to be due to the short prophylactic effect of
      CGP56697.

PMID- 9598455
TI  - First-time-in-humans safety and pharmacokinetics of WR 238605, a new
      antimalarial.
AB  - WR 238605 is an 8-aminoquinoline drug currently under development for prophylaxis
      and treatment of malaria. Preclinical studies have demonstrated that it has
      greater efficacy and less toxicity compared with primaquine. In this first-time
      in-human randomized, double-blind, placebo-controlled study designed to evaluate
      the safety, tolerance and pharmacokinetics, WR 238605 was administered to 48 men
      in single oral doses ranging from four to 600 mg (base). It was well tolerated,
      with gastrointestinal disturbances as possible side effects. Linear kinetics were
      demonstrated at these doses. WR 238605 has a long absorption phase and is slowly
      metabolized, with a tmax of 12 hr and an elimination half-life of 14 days. These
      safety, efficacy and pharmacokinetic properties make this drug an excellent
      candidate for further testing as a prophylactic, radical curative, and terminal
      eradication drug.

PMID- 9598456
TI  - A population-based seroprevalence study in South Africa as a tool in the polio
      eradication initiative.
AB  - A seroprevalence study for poliomyelitis was carried out on a sample of sera from
      a serum bank used for a vitamin A study. Vaccination coverage was satisfactory
      (80% or more) in five of nine provinces, although a prevalence of antibody to
      polio of 80% or more was found in all provinces. Serologic immunity (i.e., the
      prevalence of neutralizing antibodies) exceeded vaccination coverage, suggesting
      secondary spread of vaccine virus. However, whether or not water was supplied
      through a piped system was not associated with secondary spread of vaccine virus
      to nonvaccinated children. Seroprevalence studies are a valuable adjunct to acute
      flaccid paralysis surveillance, which is the standard surveillance instrument for
      the poliomyelitis eradication initiative. The use of available and suitable serum
      banks for seroprevalence investigations is a relatively cheap monitoring option
      that can yield very valuable information for the eradication initiative.

PMID- 9598457
TI  - Evaluation of the protective efficacy of a recombinant dengue envelope B domain
      fusion protein against dengue 2 virus infection in mice.
AB  - A recombinant protein containing part of the dengue (DEN) 2 envelope protein was
      evaluated as a subunit immunogen for vaccination against DEN virus infection. A
      gene fragment encoding amino acids 298-400 (B domain) of the DEN-2 virus envelope
      was expressed as a fusion protein with the maltose binding protein (MBP) of
      Escherichia coli. This recombinant, DEN-2(B)/MBP, was purified and analyzed for
      its antigenicity, immunogenicity, and ability to protect mice against lethal
      challenge. The recombinant antigen reacted with a DEN-2 type-specific
      neutralizing monoclonal antibody (3H5), DEN-2 hyperimmune mouse ascitic fluid,
      and DEN-2 immune human sera. When administered to mice, DEN-2(B)/MBP elicited a
      DEN-2 virus neutralizing antibody response that conferred partial protection
      against challenge infection with a lethal dose of DEN-2 virus administered by
      intracranial inoculation. In addition, no replication of DEN-2 virus was
      detectable in the brains of the immunized mice as compared with control mice that
      were killed six days after challenge. Sera from immunized mice revealed no cross
      neutralizing antibody to any of the other DEN serotypes in the plaque-reduction
      neutralization test. These findings warrant further studies with the DEN-2(B)/MBP
      antigen as a potential human vaccine candidate. An effective vaccine could
      prevent thousands of cases of illness and many deaths each year resulting from
      DEN virus infections.

PMID- 9598458
TI  - Engineered resistance in Aedes aegypti to a West African and a South American
      strain of yellow fever virus.
AB  - Double subgenomic Sindbis (dsSIN) viruses were engineered to transduce mosquito
      cells with antisense RNA derived either from the premembrane (prM) or polymerase
      (NS5) coding regions of the 17D vaccine strain of yellow fever virus (YFV). Aedes
      albopictus C6/36 cells were infected at high multiplicities of infection (MOI)
      with each dsSIN virus. Forty-eight hours later, the transduced cells were
      challenged with an MOI of 0.1 of the Asibi strain of YFV. At 72-hr postchallenge,
      the cells were assayed by immunofluorescence for the presence of YFV antigen.
      Cells transduced with prM or NS5 antisense RNAs derived from the YFV genome
      displayed no YFV-specific antigens. In contrast, cells infected with control
      dsSIN viruses that expressed no antisense RNA or dengue virus-derived antisense
      RNAs were permissive for the challenge virus. To analyze resistance in the
      mosquito, five log10 50% tissue culture infective doses (TCID50) of each dsSIN
      virus and three log10TCID50 of either a West African (BA-55) or South American
      (1899/81) strain of wild-type YFV were coinoculated into Ae. aegypti. Mosquitoes
      transduced with effector RNAs targeting the prM or NS5 gene regions did not
      transmit West African YFV and poorly transmitted the South American strain of
      YFV.

PMID- 9598459
TI  - Short report: A case of ectopic schistosomiasis in Puerto Rico with some
      observations on the biology of the parasite.
AB  - A recently acquired Schistosoma mansoni infection that resulted in a cervical
      polyp containing a pair of adult worms is reported in a Puerto Rican woman.
      Active schistosome transmission is not commonly reported in Puerto Rico at the
      present time and the ectopic location of the worms is rare in very light
      infections. Observations on the biology of the parasite recovered from the
      patient are described.

PMID- 9598460
TI  - Pathophysiology of fatal falciparum malaria in African children.
AB  - Children living in sub-Saharan Africa bear the brunt of the mortality from
      falciparum malaria, yet there is a dearth of relevant post-mortem data. Clinical
      studies from centers in Africa suggest that the pathophysiology of severe malaria
      is different in children and adults. Three overlapping clinical syndromes,
      metabolic acidosis manifesting as hyperpnea, cerebral malaria, and severe anemia,
      are responsible for nearly all the deaths in African children. Despite
      improvements in antimalarial treatment, there has not been a significant
      reduction in mortality. We review the pathology and pathophysiology of fatal
      falciparum malaria in African children. Many questions remain, the answers to
      which would facilitate the development and evaluation of new approaches to the
      management of this disease.

PMID- 9598461
TI  - Identification of a subpopulation of immune Nigerian adult volunteers by
      antibodies to the circumsporozoite protein of Plasmodium falciparum.
AB  - Collections of human sera from malaria-endemic areas would be valuable for
      identifying and characterizing antigens as malaria vaccine candidates if the
      contributing serum donors' ability to resist infection were fully characterized.
      We prepared such a serum collection from 26 apparently immune Nigerian adults who
      failed to develop patent parasitemia for at least 20 weeks following a documented
      increase in antibodies to the circumsporozoite protein (CSP) from Plasmodium
      falciparum. Volunteers were evaluated five times per week for malaria symptoms
      and bimonthly for parasites by examining thick blood smears. The incidence rate
      over 13 months for the cohort was 42% (47 malaria-confirmed volunteers) and the
      risk of infection was 1.3 infections/year. Responses to CSP did not correlate
      with protection. Because antibody responses to antigens other than CSP may be
      associated with protection, the sera from these immune individuals may be useful
      for identifying and characterizing other potential malaria vaccine candidates.

PMID- 9598462
TI  - From the lab to the clinic.

PMID- 9598463
TI  - Superficial bladder cancer: the role of interferon-alpha.
AB  - PURPOSE: We evaluate the clinical experience with recombinant interferon-alpha in
      superficial transitional cell carcinoma and discuss the most rational use of
      recombinant interferon-alpha in the context of current treatment options.
      MATERIALS AND METHODS: The available data were reviewed and discussed at a
      consensus conference in August 1996. The conclusions and recommendations are
      those of the authors based on the consensus reached at that meeting. RESULTS:
      While bacillus Calmette-Guerin (BCG) is recognized as the most efficacious
      intravesical agent in the prophylaxis and treatment of superficial transitional
      cell carcinoma, it is associated with significant toxicities and a 20 to 40%
      relapse rate. Interferons, particularly recombinant interferon-alpha, have
      demonstrated efficacy against primary and recurrent papillary transitional cell
      carcinoma and carcinoma in situ with minimal toxicity, although the response and
      relapse rates are inferior to BCG. Intravesical recombinant interferon-alpha
      therapy has also produced responses in patients who failed to respond or were
      refractory to BCG or chemotherapy. CONCLUSIONS: The clinical experience suggests
      that recombinant interferon-alpha has an important role in the treatment of
      superficial transitional cell carcinoma, particularly as second line therapy
      following failure of BCG or chemotherapy, and it may have synergistic effects
      when combined with chemotherapy or BCG. We propose a prospective randomized study
      comparing the efficacy of recombinant interferon-alpha, BCG and BCG plus
      recombinant interferon-alpha as maintenance following complete response to
      primary BCG therapy. The proposed study would also investigate the efficacy of
      BCG plus recombinant interferon-alpha as second line therapy following BCG
      failure. This study will be important to determine the most effective strategy to
      integrate recombinant interferon-alpha into current treatment options for
      superficial bladder cancer.

PMID- 9598464
TI  - Applications of electrical energy to the prostate: an evolutionary perspective.
AB  - PURPOSE: We review modern electrosurgical treatments for removing benign
      prostatic tissue based on an historical perspective of medical applications of
      electrical energy. MATERIALS AND METHODS: We reviewed historical reports and
      landmark observations concerning the evolution of medical applications of
      electrical energy in the literature, with a special focus on the development of
      principles pertinent to the transurethral electrosurgical removal of prostate
      tissue. RESULTS: Modern transurethral electrosurgery of the prostate in a fluid
      medium has been well founded on key electrosurgical principles. Traditionally,
      the best clinical results and the least complications have been obtained through
      an understanding of the important precepts of this form of energy. These precepts
      have included distinctions between the reliability of effect and safety with
      direct and alternating current, and how different tissue effects can be achieved,
      either with selective current modes (cutting and coagulating waveforms) or by
      varying the size and configuration of the active electrode and its application
      time. CONCLUSIONS: This review chronicles the prominent role of electrosurgery in
      our efforts to debulk an enlarged prostate in patients with symptomatic voiding
      dysfunction. History reminds us that many of today's "new ideas" are merely
      updated variations on a theme, have often been tried before in a fashion by our
      predecessors and have for one reason or another fallen by the wayside. The
      conundrum of the perfect combination of electrosurgical variables that can
      fulfill our goal of making this an efficient and complication-free treatment
      continues to stimulate and challenge us as we move towards the next millennium.

PMID- 9598465
TI  - Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia.
AB  - PURPOSE: The molecular mechanisms underlying the therapeutic effect of the alpha1
      blocker, doxazosin, on benign prostatic hyperplasia (BPH) are poorly understood.
      We evaluated the effect of doxazosin on cell proliferation and apoptosis in the
      prostatic glandular epithelium and stroma of patients with BPH. MATERIALS AND
      METHODS: We examined proliferative and apoptotic activities in prostate specimens
      of 22 men a mean of 65 years old with BPH before and after doxazosin treatment
      within the normal therapeutic range. Proliferative and apoptotic indexes were
      determined using Ki-67 nuclear antigen staining and the terminal transferase end
      labeling assay, respectively. The smooth muscle cell content in prostatic
      specimens was identified by smooth muscle alpha-actin, and desmin
      immunoreactivity and apoptotic indexes were correlated with prostatic stromal
      tissue regression and improvement in BPH symptoms. RESULTS: In response to
      doxazosin treatment there were no significant changes in the kinetics of cell
      proliferation in the prostatic epithelial or stromal cell population. Mean
      pretreatment baseline apoptosis was 1.9 and 1.0% for the epithelial and stromal
      prostate components, respectively. Mean apoptotic indexes significantly increased
      after 3 months of doxazosin treatment in the glandular epithelial (6%) and smooth
      muscle cells (15%). By 12 months after treatment epithelial apoptosis had
      decreased to constitutive levels, while the apoptotic index of prostatic stroma
      cells remained high. Doxazosin induced smooth muscle cell apoptosis correlated
      with prostatic stromal degeneration, decreased alpha-smooth muscle actin
      expression and improved BPH symptoms. CONCLUSIONS: These findings implicate the
      induction of prostate apoptosis by doxazosin as a potential molecular mechanism
      underlying the acute and chronic therapeutic responses of BPH to alpha1 blockade.

PMID- 9598466
TI  - Laparoscopic adrenalectomy: the retroperitoneal approach.
AB  - PURPOSE: Retroperitoneal laparoscopy, by providing direct access to the
      retroperitoneal cavity, is an interesting approach to urological surgery. We
      report our initial experience with retroperitoneal laparoscopic adrenalectomy.
      MATERIALS AND METHODS: Between January 1995 and April 1997, 23 adrenalectomies
      were performed by retroperitoneal laparoscopy in 10 men and 12 women. The
      patients were placed in the lateral decubitus position and 5 trocars were used.
      The retroperitoneal working space was created by digital dissection and was
      completed by insufflation without balloon dissection. The surgical indications
      were Conn's adenoma in 12 cases, Cushing's adenoma in 4, bilateral adrenal
      hyperplasia (Cushing's disease) in 1 (treated in a single procedure), a
      nonfunctioning adenoma in 2, pheochromocytoma in 2 and adrenal metastasis in 1.
      RESULTS: We removed 7 right and 16 left adrenal glands in an average operating
      time of 97 minutes (range 45 to 160). Average tumor size was 26 mm. (range 10 to
      40). Average hospital stay was 3.3 days (range 1 to 10). Blood loss was minimal.
      Postoperative analgesic requirements were moderate. Conversion to open surgery
      was not necessary. The morbidity rate was low, with 1 postoperative hematoma and
      1 case of persistent fever (greater than 38.5C). CONCLUSIONS: Retroperitoneal
      adrenalectomy is a reliable and effective technique. At our institution
      retroperitoneal laparoscopy is now the standard adrenal surgery procedure for
      tumors less than 5 cm.

PMID- 9598467
TI  - Supersaturation and stone composition in a network of dispersed treatment sites.
AB  - PURPOSE: We determined the validity of urine supersaturation assessed from 2, 24
      hour urine collections from outpatients eating uncontrolled diets and receiving
      care at a network of treatment sites that uses a central laboratory. We compared
      supersaturation to stone composition to determine whether supersaturation values
      correlate with composition. MATERIALS AND METHODS: Two 24-hour urine samples
      collected from 183 patients at 6 treatment sites were shipped to a single central
      laboratory. Complexations and crystallizations in vitro from aging during the
      transport step were interrupted by pH change in acid and alkaline directions.
      Relevant analytes were measured, and supersaturation was calculated for calcium
      oxalate, calcium phosphate as brushite and uric acid. Stone analysis was done at
      various laboratories. RESULTS: Urine supersaturation values correlated well with
      stone composition. Higher calcium phosphate and uric acid supersaturation was
      noted when stones contained higher amounts of calcium phosphate and any uric
      acid, respectively. In a validation study values of relevant urine materials were
      unchanged after 48 hours of aging. CONCLUSIONS: Despite the need for sample
      transport, resulting in the inevitable aging of samples, and variations in diet
      and details of sample collection, supersaturation values measured in only 2, 24
      hour urine collections accurately reflected stone composition. This finding
      indicates that supersaturation values are reasonably stable in most patients
      during the months to years required for stones to form. In addition, samples
      collected in standard practice settings and sent to a central laboratory may
      accurately reflect these supersaturation values.

PMID- 9598468
TI  - Do urinary tract infections trigger chronic kidney transplant rejection in man?
AB  - PURPOSE: Urinary tract infections are frequent after kidney transplantation but
      little is known about the impact on long-term survival. As chronic rejection is
      the major cause of graft loss in the long term, we retrospectively analyzed the
      role of urinary tract infections in this process. MATERIALS AND METHODS: We
      included in the study all adult patients who received kidney transplants at our
      unit between 1972 and 1991, which ensured followup of at least 5 years, and we
      focused on the relationship between urinary tract infections and the incidence of
      chronic rejection episodes. To analyze the influence of urinary tract infections
      on chronic rejection patients were separated into those in whom biopsy proved
      chronic rejection developed within the first 5 years after transplantation
      (chronic rejection group 225) and those without apparent signs of chronic
      rejection during that period (control group 351). The correlation between urinary
      tract infections per year and the incidence of chronic rejection was analyzed.
      RESULTS: Patients with chronic rejection had more urinary tract infections per
      year than controls. In the first year after transplantation both groups had the
      highest incidence of urinary tract infections but thereafter the rate of urinary
      tract infections per year declined. However, the incidence consistently remained
      higher in the chronic rejection group. This difference reached significance by
      year 3 after transplantation. Furthermore, a high rate of urinary tract
      infections correlated with an early onset of chronic rejection. CONCLUSIONS:
      Urinary tract infections are an important risk factor for the onset of chronic
      rejection, and early and intense treatment is critical.

PMID- 9598469
TI  - Artificial ureteral replacement for ureteral necrosis after renal
      transplantation: report of 3 cases.
AB  - PURPOSE: We applied a new minimally invasive technique of artificial ureteral
      replacement for renal transplant ureteral necrosis. MATERIALS AND METHODS:
      Artificial ureteral replacement was performed in 3 renal transplant recipients
      with ureteral necrosis (complete in 1 and distal in 2) after failure of primary
      endoscopic treatment. Under fluoroscopic guidance a percutaneous tract is created
      and progressively dilated. The ureteral silicone polytetrafluoroethylene bonded
      tube is introduced into the pyelocaliceal renal graft cavities, tracked
      subcutaneously down to the suprapubic area and introduced into the bladder via a
      short incision. RESULTS: There were no immediate postoperative complications
      except for transient postoperative acute prostatitis in 1 patient. No secondary
      complications were observed with a mean followup of 2.5 years. All grafts have
      good late function and all tubes are patent with no evidence of encrustation or
      obstruction. The tubes are well tolerated underneath the skin. Reflux was present
      in all 3 cases with no clinical manifestation. An asymptomatic episode of lower
      urinary tract infection was observed in the female patient. CONCLUSIONS: In
      select cases of ureteral necrosis after renal transplantation artificial ureteral
      replacement by subcutaneous pyelovesical bypass offers a possible alternative to
      open ureteral reconstruction.

PMID- 9598470
TI  - Combined post-chemotherapy retroperitoneal lymph node dissection and resection of
      chest tumor under the same anesthetic is appropriate based on morbidity and tumor
      pathology.
AB  - PURPOSE: We determine if post-chemotherapy resection of residual retroperitoneal
      and chest tumor under the same anesthetic is reasonable based on tumor pathology
      and morbidity, and if the finding of necrosis in the abdomen allows observation
      of chest tumor. MATERIALS AND METHODS: We retrospectively reviewed 143 post
      chemotherapy patients who underwent resection of residual retroperitoneal and
      chest disease under the same anesthetic. RESULTS: Retroperitoneal pathology was
      generally predictive of chest pathology. Concordance existed in 77.5% of patients
      with necrosis, 70% with teratoma and 69% with cancer of the abdomen. However, the
      correlation was much stronger (86%) in predicting necrosis/fibrosis if cases were
      categorized as uncomplicated by Indiana University criteria. Although the
      morbidity of the combined approach is higher than that of standard post
      chemotherapy retroperitoneal lymph node dissection, it was acceptable.
      CONCLUSIONS: The morbidity of post-chemotherapy retroperitoneal lymph node
      dissection and resection of chest disease under the same anesthetic is
      acceptable. Retroperitoneal pathology generally predicts chest pathology but this
      correlation is much stronger if the case is uncomplicated based on our criteria.
      In an uncomplicated case the discovery of necrosis of the abdomen allows
      observation of chest tumor.

PMID- 9598471
TI  - The T pouch: an orthotopic ileal neobladder incorporating a serosal lined ileal
      antireflux technique.
AB  - PURPOSE: At our institution the Kock ileal neobladder has been the primary form
      of urinary diversion after cystectomy. The few associated complications are
      primarily related to the intussuscepted antireflux afferent limb, including
      stones, stenosis and extussusception of the afferent nipple. We present a novel
      orthotopic ileal neobladder, the T pouch, with an innovative antireflux technique
      designed to prevent complications of the intussuscepted afferent nipple. MATERIAL
      AND METHODS: From November 1996 through August 1997, 40 patients an average of 67
      years old underwent construction of an orthotopic ileal neobladder (T pouch).
      Mean followup is 10.5 months (range 8 to 14). The T pouch incorporates an
      antireflux mechanism using a serosal lined ileal tunnel technique. Urinary reflux
      is prevented without ileal intussusception and with complete preservation of the
      blood supply to the afferent ileal segment. Followup in all cases includes
      clinical and functional results, and radiographic evaluation of the urinary
      reservoir and upper urinary tracts. RESULTS: One perioperative death (2.5%) and 5
      early complications (12.5%) were unrelated to urinary diversion. There have been
      no late complications. All T pouch reservoirs had excellent capacity without
      evidence of urinary reflux. The upper urinary tracts remain unchanged or improved
      in all patients. CONCLUSIONS: The T pouch is an orthotopic ileal neobladder that
      incorporates an effective, innovative antireflux mechanism created by a serosal
      lined ileal tunnel. Early clinical and functional results of this type of urinary
      diversion have been excellent. Furthermore, we suspect that this antireflux
      technique may eliminate the complications associated with an intussuscepted
      afferent nipple and maintain an effective antireflux mechanism.

PMID- 9598472
TI  - Further experience with split-cuff nipple ureteral reimplantation in urinary
      diversion.
AB  - PURPOSE: The intermediate followup results with split-cuff nipple ureteral
      reimplantation in larger numbers of urinary diversion patients are reviewed.
      MATERIALS AND METHODS: Split-cuff nipple ureteroenteric anastomosis was performed
      in 98 ureters of 51 adult patients. Mean duration of followup was 23 months
      (range 3 to 62). Two minor variations in technique compared to the original
      report are presented. RESULTS: Urinary reflux was prevented in 97.6 and 96.8% of
      cases at 1 and 2-year followup, respectively. Ureteroenteric anastomotic
      obstruction occurred in 3.1% of ureters by 3 months postoperatively. No cases of
      anastomotic leak or later obstruction occurred. Four episodes of acute
      pyelonephritis occurred in the early postoperative period. CONCLUSIONS: The split
      cuff nipple ureteral reimplant technique in urinary diversion continues to
      provide excellent results with low rates of reflux or obstruction. The 2
      described minor technical modifications further simplify the procedure.

PMID- 9598473
TI  - Does the option of the ileal neobladder stimulate patient and physician decision
      toward earlier cystectomy?
AB  - PURPOSE: The primary goal of bladder replacement is to attempt to improve patient
      quality of life, not to increase survival, affect cancer prognosis or decrease
      renal metabolic complications. Nevertheless, we retrospectively determined
      whether orthotopic bladder replacement has an impact on the decision to perform
      cystectomy. MATERIALS AND METHODS: From April 1986 to September 1994, 213 men a
      mean of 63 years old with stages pT2N0M0 to pT4N0M0 invasive bladder cancer were
      referred to our department for cystectomy. For 135 patients who underwent an
      ileal neobladder procedure and 78 who underwent conduit diversion median followup
      was 4.8 and 3.5 years, respectively. We evaluated the interval from the primary
      diagnosis of bladder cancer to cystectomy as well as the number of previous
      transurethral bladder resections. The 5-year cancer specific survival rates were
      calculated using the Kaplan-Meier method. The Wilcoxon and log rank tests, and
      the Cox proportional hazards model were used to determine statistical
      significance. RESULTS: In the neobladder and conduit groups an average of 2.1
      (range 1 to 18) and 4.1 (range 1 to 15) transurethral bladder resections was
      performed, respectively. Interval from the primary diagnosis to cystectomy was
      11.8 months in the neobladder and 16.7 months in the conduit group. Cystectomy
      was performed 4.1 months after the diagnosis of invasive cancer in the neobladder
      group, whereas radical surgery was delayed for 15.4 months in the conduit group.
      Cancer specific 5-year survival rates were 76.6 and 28.35% in the neobladder and
      conduit groups, respectively. After stratifying according to tumor stage the 5
      year survival rate was significantly higher for all disease stages in the
      neobladder than in the conduit group. The proportional hazards model revealed
      that this difference was not due to patient age at disease stages pT3bN0 and
      pT4N0 or by American Society of Anesthesiologists score. Independent prognostic
      factors for survival were diversion type and age. Delayed cystectomy was a risk
      factor only in advanced disease stages. CONCLUSIONS: These data suggest that the
      ileal neobladder may decrease physician reluctance to perform cystectomy early in
      the disease process, increasing the survival rate. They also demonstrate that the
      ileal neobladder option significantly affects an earlier patient and physician
      decision in favor of cystectomy.

PMID- 9598474
TI  - Intravesical electromotive drug administration technique: preliminary results and
      side effects.
AB  - PURPOSE: We performed intravesical electromotive drug administration (EMDA) for
      various bladder disorders during a 3-year period and assessed the technique,
      possible applications, complications and outcomes of this procedure. MATERIALS
      AND METHODS: Intravesical EMDA was performed with local anesthetics for
      transurethral surgery and in combination with dexamethasone for the treatment of
      noninfectious chronic cystitis (interstitial/radiation cystitis), with mitomycin
      C for recurrence prophylaxis of high risk superficial bladder cancer and with
      oxybutynin/bethanechol for the hyperreflexive/acontractile detrusor. A
      standardized power source and electrode catheter were used for 215 treatments in
      84 patients. RESULTS: Transurethral bladder tumor resections were pain-free in 10
      of 12 patients. Of the 25 patients with chronic noninfectious cystitis 15 were
      free of symptoms for a mean of 6.6 months, and there was a 73% increase in mean
      bladder capacity from 244 before to 421 cc after EMDA. Of the 16 patients with
      superficial bladder cancer 9 were free of recurrence for a mean of 14.1 months.
      In 10 of 14 patients with acontractile detrusors urodynamic examination showed
      detrusor contraction during EMDA of bethanechol. There were no contractions
      without electric current. EMDA of oxybutynin reduced detrusor hyperreflexia. A
      bladder ulcer was the single severe local complication and 4.6% of patients,
      mainly those with chronic cystitis, reported significant post-EMDA
      bladder/urethral pain. Minor side effects accounted for 23% of all treatments. No
      systemic side effects occurred. CONCLUSIONS: Intravesical EMDA is effective and
      innocuous. The therapeutic concept combines the advantages of increased drug
      administration without systemic side effects.

PMID- 9598475
TI  - Electromotive drug administration of lidocaine to anesthetize the bladder before
      intravesical capsaicin.
AB  - PURPOSE: The discomfort caused by intravesical capsaicin during instillation may
      restrict its use in some patients. We studied the effectiveness of using
      electromotive drug administration (EMDA) of lidocaine to anesthetize the bladder
      before capsaicin. MATERIALS AND METHODS: EMDA of lidocaine and epinephrine was
      performed in 8 patients with detrusor hyperreflexia using catheters, electrodes
      and an electrical current generator (20 mA., 15 minutes) followed immediately by
      intravesical capsaicin (2 mmol./l.) for 30 minutes under urodynamic monitoring.
      The patients scored suprapubic pain at 5 minutes and at the end of the capsaicin
      instillations on a scale of 0 to 10. Of the 8 patients 5 had had previous
      capsaicin treatments and the scores were compared to previous scores when
      intravesical lidocaine without EMDA had been used as local anesthesia before
      capsaicin. RESULTS: The pain scores during capsaicin instillations after EMDA of
      lidocaine were much lower than those during capsaicin instillations after
      lidocaine alone. EMDA virtually eliminated the hyperreflexic contractions of the
      bladder occurring during capsaicin instillations, thus reducing the risk of
      urethral leakage, and prevented autonomic dysreflexia that had previously
      occurred in 1 patient. CONCLUSIONS: EMDA of lidocaine is an effective means of
      reducing pain during subsequent intravesical capsaicin, which makes the use of
      capsaicin in the treatment of detrusor hyperreflexia more acceptable.

PMID- 9598476
TI  - The role of urinary potassium in the pathogenesis and diagnosis of interstitial
      cystitis.
AB  - PURPOSE: We determined whether intravesical potassium absorption in normal
      bladders correlates with increased sensory urgency, and corroborated the
      hypothesis that mucus is important in the regulation of epithelial permeability.
      We compared sensory nerve provocative ability of sodium versus potassium, and
      determined whether intravesical potassium sensitivity discriminates patients with
      interstitial cystitis from normal subjects and those with other sensory disorders
      of the bladder. MATERIALS AND METHODS: A total of 231 patients with interstitial
      cystitis and 41 normal subjects underwent intravesical challenge with 40 ml.
      water and then 40 ml. of 40 mEq./100 ml. potassium chloride. Subjective responses
      of urgency or pain stimulation were recorded on a scale of 0 to 5. In 19 normal
      subjects potassium absorption was measured at baseline, after injury of the
      bladder mucus with protamine, after heparin treatment to reverse mucus damage and
      then for a final time. These subjects simultaneously recorded the symptoms of
      sensory urgency and pain at baseline, after protamine and after heparin. Another
      group of normal volunteers underwent a challenge with sodium versus potassium to
      determine which cation was more provocative. Patients with bladder outlet
      obstruction secondary to benign prostatic hyperplasia (BPH), detrusor
      instability, and acute and chronic urinary tract infection but no current
      infection were also evaluated for potassium sensitivity. RESULTS: Neither normal
      subjects nor patients with interstitial cystitis reacted to water administered
      intravesically. There was marked sensitivity to intravesical potassium in 75% of
      patients with interstitial cystitis versus 4% of controls (p <0.01). Only 1
      patient with BPH responded to potassium and none of the 5 with chronic urinary
      tract infection responded. All 4 patients (100%) with a current acute urinary
      tract infection reacted positively to the potassium challenge. Of 16 patients
      with detrusor instability 25% responded. Normal subjects had minimal sensitivity
      to potassium before (11%) and markedly increased sensitivity after (79%)
      protamine treatment, and these symptoms were reversed by heparin in 42%.
      Potassium absorption directly correlated with symptoms (0.4, 3.0 and 1.3 mEq.
      before and after protamine, and after heparin reversal, respectively). In regard
      to sodium versus potassium provocation, potassium was far more provocative for
      causing urgency after protamine (10 versus 90%). Neither group underwent
      provocation before protamine. CONCLUSIONS: Chronic diffusion of urinary potassium
      into the bladder interstitium may induce sensory symptoms, damage tissue and be a
      major toxic factor in the pathogenesis of interstitial cystitis. Intravesical
      potassium sensitivity is a reliable method for detecting abnormal epithelial
      permeability. It discriminates between patients with interstitial cystitis and
      normal subjects with intact epithelial function, and it is a useful diagnostic
      test for interstitial cystitis. Potassium sensitivity correlates with increased
      potassium absorption in normal subjects, and potassium is far more provocative
      than sodium. Potassium sensitivity is also present in acute urinary tract
      infection and occasionally detrusor instability but not in BPH or chronic urinary
      tract infections.

PMID- 9598477
TI  - Anterior enterocele following cystectomy for intractable interstitial cystitis.
AB  - PURPOSE: We clinically define the development of an anterior vaginal wall hernia
      following cystectomy for the management of intractable interstitial cystitis and
      establish surgical technique for its correction. MATERIALS AND METHODS: Of 27
      women who underwent simple cystectomy and urethrectomy for intractable
      interstitial cystitis an anterior vaginal wall hernia developed in 3 (71, 56 and
      61 years old) at 8, 14 and 16 months, respectively, postoperatively. Clinical
      appearance was similar to a midline cystocele but it contained bowel contents in
      the form of an anterior enterocele. Anterior enterocele was associated with
      vaginal vault prolapse in 1 patient who was treated with transvaginal sacro
      spinous colpopexy. Patients with isolated anterior enterocele required a
      transabdominal approach with mobilization of the intestinal hernia contents and
      obliteration of the intervaginal abdominal wall space. RESULTS: At 12, 19 and 33
      months following reconstruction prolapse has not recurred, and sexual function
      was restored in 1 patient. CONCLUSIONS: These cases suggest that an extended
      simple cystectomy performed on women with intractable interstitial cystitis may
      result in a weakening of the anterior vaginal wall with resultant anterior
      enterocele formation. When it is associated with vaginal vault prolapse a
      transvaginal technique may be considered but we prefer a transabdominal approach
      for an isolated anterior enterocele. Prevention of this entity may be warranted
      at the time of cystectomy.

PMID- 9598478
TI  - Autofluorescence guided biopsy for the early diagnosis of bladder carcinoma.
AB  - PURPOSE: We validate the usefulness of laser-induced autofluorescence for the
      detection of bladder carcinoma. MATERIALS AND METHODS: We obtained and analyzed
      fluorescence spectra from 75 patients in whom bladder cancer was suspected.
      Tissue fluorescence was excited by a nitrogen laser using a quartz optical fiber
      placed in gentle contact with the area of interest. The laser-induced
      autofluorescence spectrum was recorded using an intensified optical multichannel
      analyzer system. Spectra were corrected for the spectral response of the optical
      system, and the ratios of laser-induced autofluorescence intensities (I) at 385
      and 455 nm. (I385/I455) were determined. We had previously established this ratio
      as a diagnostic algorithm. We included only suspicious bladder lesions
      (erythematous, edematous, raised and so forth) that were difficult to diagnose by
      cystoscopy as well as areas from which random biopsies were obtained. The
      fluorescence ratio algorithm was applied to 130 bladder areas. RESULTS: Of the
      130 biopsies obtained during routine cystoscopy 107 (82%) were nonmalignant by
      histological classification. In contrast, because laser-induced autofluorescence
      effectively guides biopsies towards malignant lesions, only 30 biopsies (72%
      fewer) would have been obtained from nonmalignant tissue if the fluorescence
      ratio that identifies 95% of malignant lesions (95th percentile) had been
      selected as the decision criterion during standard cystoscopy. CONCLUSIONS: By
      guiding the surgeon to suspicious lesions that are most likely to be malignant,
      laser-induced autofluorescence substantially decreases the number of biopsies
      obtained from nonmalignant tissue during cystoscopy to diagnose bladder
      carcinoma.

PMID- 9598479
TI  - Can urine bound diagnostic tests replace cystoscopy in the management of bladder
      cancer?
AB  - PURPOSE: We compare the diagnostic value of NMP22 and BTA stat testing, and
      QUANTICYT computer assisted dual parameter image analysis to cytology and
      cystoscopy in patients who had symptoms suggestive of transitional cell cancer or
      were being followed after treatment for that disease. MATERIALS AND METHODS: We
      prospectively evaluated voided urine and/or barbotage specimens from 291 patients
      a mean of 65.2 years old. All voided urine samples were evaluated by quick
      staining and standard cytology, the BTA stat 1-step qualitative assay (which
      detects a bladder tumor associated antigen) and the NMP22 test (which detects a
      nuclear mitotic apparatus protein). In addition, barbotage specimens were
      evaluated by QUANTICYT computer assisted dual parameter image analysis. All
      patients underwent subsequent cystoscopy and biopsy evaluation of any suspicious
      lesion. Sensitivity, specificity, and the predictive value of positive and
      negative results were determined in correlation with endoscopic and histological
      findings. RESULTS: In 91 patients with histologically proved transitional cell
      carcinoma overall sensitivity was 48, 57, 58, 59 and 59% for the NMP22 test, the
      BTA stat test, rapid staining cytology of barbotage samples, rapid staining
      cytology of voided urine specimens and image analysis, respectively. For
      histological grades 1 to 3 underlying transitional cell carcinoma sensitivity was
      17, 61 and 90% for urinary cytology, 48, 58 and 63% for the BTA stat test, and
      52, 45 and 50% for the NMP22 test, respectively. Specificity was 100% for
      cytology, 93% for image analysis, 70% for the NMP22 test and 68% for the BTA stat
      test. CONCLUSIONS: Immunological markers are superior to cytological evaluation
      and image analysis for detecting low grade transitional cell carcinoma but they
      have low specificity and sensitivity in grade 3 transitional cell carcinoma.
      Urine bound diagnostic tools cannot replace cystoscopy.

PMID- 9598480
TI  - Bladder cancer in patients with multiple sclerosis treated with cyclophosphamide.
AB  - PURPOSE: We define the risk of bladder cancer in multiple sclerosis related to
      the use of indwelling catheters and cyclophosphamide administered as an
      immunomodulating agent. MATERIALS AND METHODS: We retrospectively reviewed the
      records of 2,351 patients with multiple sclerosis referred to the National Center
      for Multiple Sclerosis. RESULTS: Of the 2,351 patients 2 women and 5 men (0.29%)
      had bladder cancer. Of the 850 chronically catheterized patients the incidence
      was 0.7%. One patient with cancer performed intermittent catheterization for a
      rate of 0.23% in this group. In a subgroup of 70 patients treated with
      cyclophosphamide 5 chronically catheterized patients (5.7%) had bladder cancer.
      Hematuria was the most common presenting symptom. These data were compared with
      those in the literature on bladder cancer in spinal cord injury. CONCLUSIONS:
      These data suggest a possible synergistic role of cyclophosphamide and chronic
      catheterization in the induction of secondary bladder cancer. Regular cystoscopy
      is warranted in these patients to allow early detection of bladder tumors. Nitric
      oxide metabolism may be an important factor in the carcinogenesis of this type of
      bladder cancer.

PMID- 9598481
TI  - Superficial bladder tumors and increased reactivity against mycobacterial
      antigens before bacillus Calmette-Guerin therapy.
AB  - PURPOSE: The precise mechanism of action of bacillus Calmette-Guerin (BCG) in
      bladder cancer treatment remains poorly understood. Whether bladder tumor cells
      are destroyed by nonspecific mechanisms or targeted by specifically activated
      lymphocytes recognizing cognate antigens is unclear. To investigate a possible
      cross-reactivity between BCG and bladder cell tumors, we tested before BCG
      treatment the lymphoproliferation of peripheral blood lymphocytes against several
      mycobacterial antigens, including the secreted fibronectin binding antigen 85
      complex from BCG (AG 85) in patients with superficial bladder tumors compared to
      control matched patients. MATERIALS AND METHODS: Using a whole blood assay, T
      cell response against purified protein derivative, BCG extract, whole BCG,
      purified AG 85, and the nonspecific mitogens pokeweed and phytohemagglutinin was
      investigated in 79 patients with superficial bladder tumors before BCG and in 39
      control subjects without malignancy matched for age and sex. Neither group had a
      history of tuberculosis. Lymphoproliferation was measured with a tritiated
      thymidine uptake assay on day 7 of culture. RESULTS: Of the 79 patients with
      superficial transitional cell carcinoma, a significant lymphoproliferative
      response before BCG against PPD, BCG extract, whole BCG and AG 85 was observed in
      65 (82.2%), 67 (84.81%), 30 (37.97%) and 49 (62.02%) patients, respectively. Of
      the 39 controls only 26 (64.1%), 23 (58.9%), 3 (7.7%) and 3 (7.7%) patients,
      respectively, had a significant lymphoproliferation against PPD, BCG extract, BCG
      and AG 85 (p >0.05, p = 0.004, p = 0.00001 and p = 0.00001, respectively). In
      terms of lymphoproliferative levels, patients with superficial transitional cell
      carcinoma also showed a significantly higher response against PPD (p = 0.000012),
      BCG extract (p = 0.000001), AG 85 (p = 0.000001), whole BCG (p = 0.00001) and
      pokeweed (p = 0.01) than controls but not against phytohemagglutinin.
      CONCLUSIONS: Patients with superficial transitional cell carcinoma demonstrate an
      increased lymphoproliferation against mycobacterial antigens before BCG compared
      to control subjects. Although a nonspecific activation of the immune system
      cannot be excluded at this stage, our data may suggest the possible existence of
      bladder cancer antigens cross-reactive with mycobacterial antigens responsible
      for boosting precursor cells witnessing previous contacts with mycobacteria. The
      implication of these findings in the antitumoral mechanism of action of BCG are
      under investigation.

PMID- 9598482
TI  - Anatomical relationship between urethra and clitoris.
AB  - PURPOSE: We investigated the anatomical relationship between the urethra and the
      surrounding erectile tissue, and reviewed the appropriateness of the current
      nomenclature used to describe this anatomy. MATERIALS AND METHODS: A detailed
      dissection was performed on 2 fresh and 8 fixed human female adult cadavers (age
      range 22 to 88 years). The relationship of the urethra to the surrounding
      erectile tissue was ascertained in each specimen, and the erectile tissue
      arrangement was determined and compared to standard anatomical descriptions.
      Nerves supplying the erectile tissue were carefully preserved and their
      relationship to the soft tissues and bony pelvis was noted. RESULTS: The female
      urethra, distal vaginal wall and erectile tissue are packed into the perineum
      caudal (superficial) to the pubic arch, which is bounded laterally by the
      ischiopubic rami, and superficially by the labia minora and majora. This complex
      is not flat against the rami as is commonly depicted but projects from the bony
      landmarks for 3 to 6 cm. The perineal urethra is embedded in the anterior vaginal
      wall and is surrounded by erectile tissue in all directions except posteriorly
      where it relates to the vaginal wall. The bulbs of the vestibule are
      inappropriately named as they directly relate to the other clitoral components
      and the urethra. Their association with the vestibule is inconsistent and, thus,
      we recommend that these structures be renamed the bulbs of the clitoris.
      CONCLUSIONS: A series of detailed dissections suggest that current anatomical
      descriptions of female human urethral and genital anatomy are inaccurate.

PMID- 9598483
TI  - Management of obliterative posttraumatic posterior urethral strictures after
      failed initial urethroplasty.
AB  - PURPOSE: We evaluate the problems encountered during surgery and assess the
      results of different endoscopic and open surgical methods following failed
      urethroplasty for posttraumatic posterior urethral stricture. MATERIALS AND
      METHODS: Since 1992 we have treated 23 patients in whom urethroplasty for
      posterior urethral strictures failed. Of these patients, 3 had undergone 2
      previous repairs and 6 had additional complicating factors, such as fistula,
      periurethral cavity and false passage. End-to-end anastomosis was done in 14
      patients via a transperineal (7) or transpubic (7) approach. In 1 patient
      substitution urethroplasty using a radial artery based forearm free flap was
      performed. In 3 patients a 2-stage urethroplasty was done, 4 underwent core
      through optical internal urethrotomy and 1 underwent endoscopic marsupialization
      of a false passage. RESULTS: At 1 to 5-year followup 3 of the 23 patients had
      restenoses (13%), including 2 in whom previous treatment failed. The remaining
      87% of the patients void well and are continent, and there is no worsening of the
      preexisting potency status. CONCLUSIONS: Previous failed urethral stricture
      repair complicates management due to fibrosis, impaired vascularity and limited
      urethra available for mobilization. Recurrent strictures less than 1.5 cm. can be
      managed successfully with core-through internal urethrotomy. End-to-end
      anastomosis is possible in the majority with generous use of inferior pubectomy
      or the transpubic approach with certain modifications. When residual inflammation
      or long strictures are present a 2-stage procedure is a safer option. Overall,
      reoperation can offer a successful outcome for the majority of these complex
      strictures.

PMID- 9598484
TI  - Accuracy of survey questions for geriatric urinary incontinence.
AB  - PURPOSE: Risk factors, natural history, consequences, therapeutic responses and
      costs are all likely related to type of urinary incontinence, for example stress
      or urge. Yet few epidemiologic type specific data are available and only 1 study
      has been validated urodynamically. We compare the accuracy of a typical
      questionnaire used in a large epidemiologic study with the criterion standard of
      multichannel video urodynamic testing. MATERIALS AND METHODS: The questionnaire
      was administered before urodynamic testing to 132 subjects 65 years old or older,
      of whom 80% were women, all were mobile and none was severely demented. Responses
      to questionnaire items were compared to the criterion standard, singly and in
      combination, using a total of 4 a priori and post hoc strategies, including a
      computerized regression tree program. RESULTS: Overall, no analytic strategy
      correctly classified more than 67% of patients and none accurately classified
      even a single type of incontinence, including stress incontinence. CONCLUSIONS:
      Short questionnaires commonly used in epidemiologic studies correlated poorly
      with video urodynamic testing in incontinent older adults. Previously published
      information regarding prevalence of the types of incontinence should be reviewed
      in the light of these data.

PMID- 9598485
TI  - Variations in Valsalva leak point pressure with increasing vesical volume.
AB  - PURPOSE: Although leak point pressure testing is a valuable tool in the diagnosis
      of female stress urinary incontinence, little standardization in methodology
      exists. We examined the effect of vesical volume on leak point pressure to assess
      the need for determining an optimal volume for leak point pressure testing.
      MATERIALS AND METHODS: Video urodynamic testing was performed in 52 consecutive
      women with a mean age of 52 years who presented with stress urinary incontinence.
      By fluoroscopic criteria stress urinary incontinence was type I in 12 patients,
      type II in 20 and type III in 20. Leak point pressure determined at 50 cc volume
      increments was correlated with fluoroscopic criteria. RESULTS: Women with type I
      stress urinary incontinence had high leak point pressure, which remained high at
      increasing vesical volumes, and those with type III had low leak point pressure,
      which remained low at increasing volumes. In patients with type II incontinence
      initially high leak point pressure decreased significantly at increasing vesical
      volumes. The most appropriate classification of patients occurred at a volume of
      250 to 300 cc. CONCLUSIONS: Leak point pressure is affected by vesical volume. At
      a volume of 250 to 300 cc leak point pressure correlates best with fluoroscopic
      findings, and it may be used to guide therapy in women presenting with stress
      urinary incontinence.

PMID- 9598486
TI  - Peripheral distribution of the human dorsal nerve of the penis.
AB  - PURPOSE: The integrity of the dorsal nerve of the penis is crucial for normal
      erectile and ejaculatory function. To our knowledge a description of this nerve
      along the phallus has not been formally described. We illustrate the distribution
      of the dorsal nerve of the penis to the penile shaft, anterior urethra and glans.
      MATERIALS AND METHODS: Neuroanatomical dissections were performed on 28 cadaver
      penis specimens. Electrodiagnostic testing was conducted on 10 healthy male
      subjects to confirm the anatomical findings. RESULTS: The dorsal nerve of the
      penis consists of 2 populations of axons, one to innervate the penile shaft and
      urethra, and the other to innervate the glans. Stimulation of the urethra
      resulted in responses recorded in the main trunk of the dorsal nerve of the penis
      and stimulation of the nerve evoked responses within the urethra. Bulbocavernosus
      muscle contraction was elicited following urethral stimulation. CONCLUSIONS:
      Urethral innervation by the dorsal nerve of the penis supports the view that
      urethral afferent impulses are a component of reflex ejaculatory activity. The
      pattern of glanular innervation by the dorsal nerve of the penis identifies the
      glans as a sensory end organ for sexual reflexes. The undulating character of the
      dorsal nerve of the penis is a mechanism by which the nerve can accommodate to
      significant changes in penile length with erection. Electrodiagnostic studies of
      the dorsal nerve of the penis should be modified to consider the anatomical
      findings.

PMID- 9598487
TI  - Median raphe (parameatal) cysts of the penis.
AB  - PURPOSE: Although median raphe cysts of the penis have been widely reported the
      pathogenesis is obscure. We describe the microstructural detection of 3 cases of
      median raphe to study the true pathogenesis. MATERIALS AND METHODS: Three
      patients presented to our clinic of plastic surgery complaining of abnormal shape
      of the penis or mass recurrence. High magnification light microscopy and electron
      microscopy were performed. RESULTS: Microstructural study revealed that all 3
      cases had similar findings to those of the common urethral mucosa. CONCLUSIONS:
      Median raphe cysts are derived from the external paraurethral ducts and contain
      features that to our knowledge have not been previously reported.

PMID- 9598488
TI  - Nocturnal penile tumescence and rigidity monitoring in young potent volunteers:
      reproducibility, evaluation criteria and the effect of sexual intercourse.
AB  - PURPOSE: We studied the reproducibility of nocturnal penile tumescence, rigidity
      evaluation criteria and the possible effects of sexual intercourse in young,
      healthy, potent male volunteers. MATERIALS AND METHODS: We recruited 12 male
      medical students 21 to 24 years old into the study. A disorder-free medical
      history, availability of a sexual partner and normal erectile function were the
      inclusion criteria. All subjects completed 3 sessions of 3 nights of recording
      using the RigiScan* device with at least a 3-day interval between recordings.
      During the last 3-night recording subjects were asked to have sexual intercourse
      at least once. Analysis of the recordings was focused on the best erectile event
      as well as on rigidity and tumescence activity units normalized per hour.
      RESULTS: The subjects completed 36, 3-night recordings. Of the total of 108
      sessions 18 occurred after sexual intercourse. We analyzed 562 erectile episodes.
      All 3-night recordings included at least 1 episode of rigidity at the penile tip
      greater than 60% and more than 10 minutes in duration. Sexual intercourse did not
      significantly affect nocturnal penile tumescence and rigidity. When rigidity and
      tumescence activity unit values were normalized by the hour and expressed as mean
      values of the 3-night sessions, documented values became reproducible.
      CONCLUSIONS: At least 2 consecutive nights of recording are necessary to evaluate
      nocturnal penile tumescence and rigidity recordings. Nocturnal penile tumescence
      and rigidity with at least 1 erectile episode of tip penile rigidity greater than
      60% and 10 minutes in duration may be associated with potency. Mean rigidity and
      tumescence activity unit values per hour of a recording may be used as objective
      parameters to measure overall erectile activity. In addition, sexual intercourse
      seems to decrease nocturnal penile tumescence and rigidity measurements, although
      not statistically significant. We anticipate that application of these criteria
      for nocturnal penile tumescence and rigidity evaluation will improve the
      diagnostic validity of the test. Future research will determine whether these
      criteria are too strict for the evaluation of aging men.

PMID- 9598489
TI  - Treatment of erectile dysfunction after kidney transplantation with
      intracavernosal self-injection of prostaglandin E1.
AB  - PURPOSE: We evaluate the results of treatment of erectile dysfunction in kidney
      transplant patients with intracavernosal self-injection of vasoactive drugs.
      MATERIALS AND METHODS: We evaluated and treated 26 male kidney transplant
      patients for erectile dysfunction. All patients had stable kidney function 6 to
      75 months (mean 26.6 +/- 9) after transplantation. Each patient received an
      intracavernosal injection of 20 microg. prostaglandin E1 (PGE1), and after 20 to
      30 minutes the response was assessed. Nonresponders received 40 microg. PGE1 at
      another visit, and those who showed no response were reinjected with 40 microg.
      PGE1 plus 30 mg. papaverine hydrochloride. A total of 21 patients were enrolled
      in a self-injection program and have been followed between 3 and 21 months (mean
      11.6 +/- 2.7). RESULTS: Hormonal alterations were seen in 7 patients with serum
      testosterone as low as 16.6 ng./ml. (normal 33 to 100), and testosterone
      injections gave only marginal response in 2. Intracavernosal injection of 20
      microg. PGE1 provided good response in 15 patients (57.7%), while 40 microg. PGE1
      alone or in combination with 30 mg. papaverine resulted in good response in
      another 6 and 2 patients, respectively. Among the 21 patients who were enrolled
      in the self-injection program 19 (90.5%) reported complete satisfaction with no
      adverse local or systemic complications except for local pain at the injection
      site in 4. There has been no change in serum creatinine, cyclosporine level or
      doses of immunosuppression medications during the observation period.
      CONCLUSIONS: Intracavernosal self-injection of PGE1 is well accepted and
      tolerated by kidney transplant patients. It poses no apparent risks to the
      transplanted kidney and could be a good modality to treat erectile dysfunction in
      kidney transplant recipients.

PMID- 9598490
TI  - An analysis of 653 trials of penile vibratory stimulation in men with spinal cord
      injury.
AB  - PURPOSE: We evaluated ejaculatory response and semen quality in 653 trials of
      penile vibratory stimulation in 211 men with spinal cord injury, and compared
      results with low versus high amplitude vibratory stimulation. MATERIALS AND
      METHODS: Low and/or high amplitude penile vibratory stimulation was performed 1
      to 27 times in each patient, and antegrade and retrograde specimens of those who
      ejaculated were analyzed. RESULTS: Significantly more patients ejaculated using
      high (54.5%) versus low (39.9%) amplitude stimulation. Using either amplitude the
      ejaculatory success rate was highest in men with injuries at C3 to C7, followed
      by T1 to T5, T6 to T10 and T11 to L3. While high amplitude stimulation increased
      the ejaculatory success rate in each group, the highest rate occurred in men with
      injuries at C3 to C7 (65.6%). Ejaculation was reliable, since most men who
      ejaculated did so during 100% of the trials and within 2 minutes of stimulation
      onset. Symptoms of autonomic dysreflexia were safely managed with nifedipine. All
      patients who ejaculated produced antegrade specimens. With the exception of
      ejaculate volume, which was significantly higher with high versus low amplitude
      stimulation, semen parameters were similar using both vibrator amplitudes.
      CONCLUSIONS: Ejaculatory success is better while semen quality is similar using
      high versus low amplitude penile vibratory stimulation in men with spinal cord
      injury. This method may be considered first line treatment for anejaculation in
      men with spinal cord injury due to its safety, relative effectiveness, and
      relatively low investment of time and money.

PMID- 9598491
TI  - Treatment of premature ejaculation with sertraline hydrochloride: a single-blind
      placebo controlled crossover study.
AB  - PURPOSE: The efficacy of sertraline hydrochloride for the treatment of premature
      ejaculation is evaluated. MATERIALS AND METHODS: A total of 37 potent men, 19 to
      70 years old (mean age 41), with premature ejaculation were treated with 50 mg.
      oral sertraline and placebo in a controlled randomized single-blind crossover
      trial. All men were either married or in a stable relationship. None of the
      patients received any formal psychosexual therapy. Chronic open label treatment
      with sertraline was continued in 29 patients who had achieved an increase in
      ejaculatory latency times over pretreatment levels with active drug in the
      initial crossover study. In an attempt to identify which patients could maintain
      the improved ejaculatory control after withdrawal of the active drug, serial drug
      withdrawal was conducted every 4 weeks with drug initiation after a further 2
      weeks if improved ejaculatory control was not maintained. RESULTS: The mean
      pretreatment ejaculatory latency time was 0.3 minute (range 0 to 1). The mean
      ejaculatory interval after 4 weeks of treatment was 3.2 minutes (range 1 minute
      to anejaculation) with sertraline and 0.5 minute (range 0 to 1) with placebo (p
      <0.001). Intravaginal ejaculation was achieved for the first time in 5 patients
      with primary premature ejaculation and 2 patients experienced anejaculation. One
      patient described minor drowsiness and anorexia, and 2 patients described mild,
      transient gastrointestinal upset. Staged drug withdrawal allowed 20 of the 29
      patients (67%) on chronic open label treatment with sertraline to discontinue the
      drug after a mean interval of 7.3 months with a mean ejaculatory latency time of
      4.1 minutes (range 1 to 12). CONCLUSIONS: Sertraline appears to be a useful agent
      in the pharmacological treatment of premature ejaculation.

PMID- 9598492
TI  - Susceptibility to idiopathic azoospermia in Japanese men is linked to HLA class I
      antigen.
AB  - PURPOSE: Approximately 15 to 20% of infertile men have azoospermia. In the Y
      chromosome a deletion, termed the azoospermic factor, has been found in some
      cases of idiopathic azoospermia. We investigate the relationship of factors in
      autosomal chromosomes (HLA class I antigens) to spermatogenesis failure in
      idiopathic azoospermia. MATERIALS AND METHODS: We evaluated 65 infertile Japanese
      men with idiopathic azoospermia. The frequency of the HLA allele reported in
      1,216 healthy Japanese men was used as a control. HLA class I typing was
      performed by the National Institutes of Health standard serological method or
      polymerase chain reaction-sequence specific primer analysis. Allele frequencies
      were calculated. We determined statistical significance in the frequency of each
      allele in patients and controls using the chi-square test. The relationship of
      HLA antigens to idiopathic azoospermia was expressed as relative risk. RESULTS:
      In Japanese men with idiopathic azoospermia the frequency of HLA-A33, B13 and B44
      was significantly increased compared with controls. The relative risk of HLA-B44
      was 8.4, an extremely high value compared with that of other diseases and HLA
      antigens. CONCLUSIONS: We suggest that HLA class I antigens are important genetic
      markers that represent a risk factor for idiopathic azoospermia.

PMID- 9598493
TI  - Pretreatment follicle-stimulating hormone: a prognostic serum marker of
      spermatogenesis status in patients treated for germ cell cancer.
AB  - PURPOSE: We evaluate the use of pretreatment follicle-stimulating hormone (FSH)
      in patients with germ cell tumors as a prognostic serum marker of spermatogenesis
      after standard treatment. Additionally, Leydig cell function was investigated by
      estimation of luteinizing hormone (LH) and testosterone (T), and calculation of
      the T/LH ratio. MATERIALS AND METHODS: Serum FSH, LH and T were determined
      radioimmunologically associated with semen analyses in 20 patients with seminoma
      (pathological stages IA to IIB) after unilateral orchiectomy before and up to 24
      months after infradiaphragmatic radiotherapy. Additionally, hormone analyses were
      performed in 18 patients with nonseminomatous germ cell tumor (pathological
      stages IIA to C) before and up to 36 months after standard cisplatin based
      chemotherapy. RESULTS: Seminoma patients undergoing radiotherapy were divided
      into 2 groups consisting of 12 patients with normal pretreatment serum FSH and 8
      with elevated FSH reflecting spermatogenesis deficits even before treatment. Six
      months after irradiation a significant increase in FSH (p <0.01) associated with
      a decrease in sperm density was observed in both groups and 24 months after
      radiotherapy patients with initially normal FSH had significantly lower serum FSH
      (p <0.01) associated with higher sperm density than those with initially elevated
      FSH (p <0.01), indicating less impairment of Sertoli cell function. Comparable
      results were observed in chemotherapy treated germ cell tumor patients with
      initially normal (11) and elevated serum FSH (7), respectively, and 36 months
      after chemotherapy patients with initially normal FSH had significantly lower FSH
      concentrations than those with initially elevated FSH (p <0.01). Compensated
      impairment of Leydig cell function reflected by a subnormal T/LH ratio was
      evident before chemotherapy in 16.7% of patients increasing up to 41.2% 36 months
      after therapy. In contrast, 24 months after radiotherapy only 25% of seminoma
      patients showed a subnormal ratio reflecting less damage to the Leydig cells
      caused by irradiation. CONCLUSIONS: Pretreatment FSH is a prognostic serum marker
      of spermatogenesis status of germ cell tumor patients receiving standard
      radiotherapy or chemotherapy. In contrast to seminoma patients after
      radiotherapy, impairment of Leydig cell function was evident in germ cell tumor
      patients after cisplatin based chemotherapy.

PMID- 9598494
TI  - Psychosocial adjustment after testicular cancer treatment.
AB  - PURPOSE: The high cure rate in testicular cancer has provoked investigations
      relating to the quality of life in long-term survivors. We determine the
      psychosocial consequences of the disease especially in regard to sexual and
      professional performance. MATERIALS AND METHODS: Among the testicular cancer
      patients treated with various treatment modalities 140 rendered free of disease
      for at least a year were included in this study. General Health Questionnaire 28
      and a general survey were used to determine quality of life issues. RESULTS:
      Regarding the sexual life of these patients, problems related to libido, erection
      and ejaculation increased significantly during treatment and subsequently
      recovered but did not return to baseline after treatment. During treatment the
      frequency of sexual intercourse and/or masturbation decreased significantly in
      all patients. Of the single patients 35% thought that medical history would be a
      concern for the potential spouse. Regarding professional lives, 22.4% thought
      that they had better performance after treatment compared to before therapy,
      whereas only 6.1% reported it to be worse. When professional performance was
      analyzed according to the treatment modalities those who had received
      radiotherapy did worse. General Health Questionnaire scores indicated that
      patients with this disease had a positive view of life compared to that of the
      normal population. CONCLUSIONS: Although we observed a substantial recovery in
      sexual life after treatment, it was evident that therapy did have a negative
      effect on sexual functions. There was no effect on occupational performance and
      perspective of life, which may be related to the fact of having overcome a life
      threatening disease.

PMID- 9598495
TI  - Triangulation end-to-side vasoepididymostomy.
AB  - PURPOSE: A technique and the preliminary results of triangulation
      vasoepididymostomy are described. MATERIALS AND METHODS: Triangulation
      vasoepididymostomy is performed by placing 3 double-armed 10-zero nylon sutures
      into the epididymis so that each suture forms 1 side of a triangle. An opening in
      the tubule is made between the sutures and they are brought inside-out,
      invaginating the epididymal tubule into the vas deferens. RESULTS: Triangulation
      end-to-side vasoepididymostomy was performed bilaterally in 12 men, and sperm was
      found in the postoperative ejaculate of 11 (92%). Operative time was 156 +/- 14
      minutes. CONCLUSIONS: Triangulation vasoepididymostomy is reasonably successful
      in restoring sperm to the ejaculate and should be considered as an alternative
      method of vasoepididymostomy.

PMID- 9598496
TI  - Granulomatous epididymo-orchitis: sonographic features and clinical outcome in
      brucellosis, tuberculosis and idiopathic granulomatous epididymo-orchitis.
AB  - PURPOSE: We reviewed and analyzed sonographic findings in granulomatous epididymo
      orchitis in an attempt to differentiate this rare inflammatory entity from other
      causes of enlarged scrotum, such as tumors. MATERIALS AND METHODS: We
      retrospectively reviewed sonographic features of 9 patients a mean of 41 years
      old with specific and nonspecific granulomatous epididymo-orchitis, including
      brucellosis in 7, tuberculosis in 1 and idiopathic granulomatous epididymo
      orchitis in 1. Histological confirmation was obtained in 3 cases, and in the
      remaining 6 positive clinical manifestations and laboratory tests for brucellosis
      were accepted as the main criteria for the diagnosis of brucellar epididymo
      orchitis. RESULTS: The most notable echographic finding was an enlarged and
      heterogeneous epididymis, predominantly in the body and tail. Testicular
      involvement consisted of a diffusely hypoechoic testis or focal intratesticular
      areas. Thickening of the scrotal wall and tunica albuginea, and moderate
      hydrocele were also noted occasionally. Followup scans revealed intratesticular
      abscesses in 3 patients. CONCLUSIONS: These echographic findings may suggest the
      diagnosis of granulomatous epididymo-orchitis in the appropriate clinical
      setting, and help to avoid unnecessary orchiectomy for benign disease.

PMID- 9598497
TI  - Current and future trends in interventional therapy for benign prostatic
      hyperplasia in Japan.
AB  - PURPOSE: Procedures of Japanese urologists of interventional therapy for benign
      prostatic hyperplasia (BPH) should be defined for resource economy and policy
      establishment. MATERIALS AND METHODS: A questionnaire was mailed to the urology
      departments of 80 medical schools in Japan for clarification of surgical
      procedures presently in use for treating bladder outlet obstruction due to BPH.
      Prospects for the next 5 years (year 2002) were also requested. RESULTS: We
      received 76 questionnaire responses from medical school urology facilities (95%)
      by the end of January 1997. Standard transurethral resection of the prostate
      gland is and will continue to be the most common surgical procedure. Open
      adenectomy is the first choice for large glands but may be replaced by other
      interventional procedures. Laser prostatectomy and transurethral
      electrovaporization will be used more often for treating all severities of BPH.
      CONCLUSIONS: Even with increasing interest in new techniques, transurethral
      resection of the prostate will continue to serve as the standard therapy for BPH
      during the next 5 years. Transurethral electrovaporization may become established
      in the near future.

PMID- 9598498
TI  - Interstitial laser coagulation for management of benign prostatic hyperplasia: a
      Japanese experience.
AB  - PURPOSE: The principle of interstitial laser coagulation is to shrink the
      prostate by generating intraprostatic necrosis without damaging the urethra or
      causing tissue sloughing. The clinical efficacy and durability of interstitial
      laser coagulation in the treatment of benign prostatic hyperplasia (BPH) were
      evaluated. MATERIALS AND METHODS: From December 1993 to June 1996, 76 patients
      with symptomatic BPH were treated with interstitial laser coagulation. A
      neodymium:YAG laser was used in combination with a specially designed
      interstitial thermotherapy light guide. The tip of the light guide was inserted
      into each lobe of the prostate transurethrally under direct vision. All
      evaluations were made at baseline and then 1, 3, 6 and 12 months after therapy.
      Treatment outcome was evaluated by International Prostate Symptom Score (I-PSS),
      flow rate and post-void residual urine volume. Disease specific quality of life
      was assessed via a quality of life assessment score and a BPH impact index.
      Independent of symptom assessment, a self-reporting questionnaire was prepared at
      3 months postoperatively regarding satisfaction with treatment and sexual
      function. RESULTS: Among 44 patients followed to 12 months the mean I-PSS
      significantly decreased from 20.4 at baseline to 7.4, representing 64%
      improvement (p <0.001). Peak flow rate increased by 50% from a preoperative
      average of 7.4 to 11.1 ml. per second at 12 months in 42 patients (p <0.001). The
      post-void residual volume decreased by 57% from 102 to 44 ml. at 12 months in 40
      cases (p <0.001). Steady and progressive improvement was observed on quality of
      life assessment and BPH impact index scores at 3, 6 and 12 months. No patients
      reported new onset of erectile dysfunction. No serious side effects were
      observed, except for loss of ejaculation in 3 cases and seminal vesicle abscess
      in 1. Only 6 patients (8%) required re-treatment for persisting obstructive
      symptoms during 12 months of followup. A recent change in methods towards more
      aggressive treatment plausibly influenced the outcomes to require less repeat
      treatment. CONCLUSIONS: After the interstitial laser coagulation procedure
      satisfactory results were obtained and improvement lasted through 12 months.
      Although the optimal number of fiber placements for each prostate is not known,
      more aggressive treatment appears to provide better outcomes.

PMID- 9598499
TI  - Long-term results of lower energy transurethral microwave thermotherapy.
AB  - PURPOSE: We evaluate long-term results of lower energy transurethral microwave
      thermotherapy (Prostasoft 2.0*) and identify pretreatment characteristics that
      predict a favorable outcome. MATERIALS AND METHODS: Between December 1990 and
      December 1992, 231 patients with lower urinary tract symptoms were treated with
      lower energy transurethral microwave thermotherapy. Subjective and objective
      voiding parameters were collected from medical records and a self-administered
      questionnaire. Kaplan-Meier plots were constructed to assess the risk of re
      treatment. RESULTS: Of the patients 41% underwent invasive re-treatment within 5
      years of followup and 17% were re-treated with medication. The re-treatment-free
      period was somewhat longer in patients with a peak flow rate greater than 10 ml.
      per second, a Madsen score 15 or less, a post-void residual volume 100 ml. or
      less and age greater than 65 years at baseline. Prostate volume did not modify
      the outcome. No incontinence was caused by transurethral microwave thermotherapy,
      8% had recurrent urinary tract infection and 8% had retrograde ejaculation. Only
      1 patient had a urethral stricture after transurethral microwave thermotherapy.
      CONCLUSIONS: At 5 years after transurethral microwave thermotherapy 41% of the
      patients received instrumental treatment. Patients with a lower Madsen score and
      lower residual volume, and those with higher peak flow and age were somewhat
      better responders to lower energy transurethral microwave thermotherapy.

PMID- 9598500
TI  - Catheter-free endoscopic laser ablation of the prostate using a 1-size prostatic
      stent.
AB  - PURPOSE: Endoscopic laser ablation of the prostate is a safe alternative to
      transurethral prostatic resection. Recognized disadvantages include prolonged
      catheterization, postoperative discomfort and delayed symptomatic improvement. We
      assessed the role of a 1-size temporary prostatic stent in men undergoing
      endoscopic laser ablation of the prostate. MATERIALS AND METHODS: A total of 55
      men a mean of 73 years old with outflow obstruction, including 9 who presented in
      urinary retention, underwent endoscopic laser ablation of the prostate and
      temporary stenting. Urinary flow rate, residual urine volume, symptom score and
      prostate specific antigen were measured preoperatively, and 6 weeks (with the
      stent in situ), 3 months (after stent removal) and 12 months postoperatively.
      Duration of hospital stay and complications were also recorded. RESULTS: Of the
      55 men 37 (67%) voided immediately with the stent in situ, including 7 of the 9
      in retention. At 6 weeks with the stent in place mean maximum urine flow was 17.3
      ml. per second (preoperatively 8.7). Dysuria was reported by 3 patients. Stent
      related complications were rare. One stent migrated early, resulting in urinary
      retention, while 2 that migrated late were asymptomatic. No patient had acute
      urinary retention after stent removal. Maximum urinary flow rate measured at 6
      weeks with the stent in situ was similar to that 1 year after endoscopic laser
      ablation of the prostate. CONCLUSIONS: The use of a 1-size, inexpensive plastic
      prostatic stent enabled catheter-free endoscopic laser ablation of the prostate
      in 67% of our patients. Early improvements in the urinary flow rate and a lower
      incidence of dysuria were additional benefits. The result of endoscopic laser
      ablation of the prostate at 1 year was comparable to that of transurethral
      prostatic resection.

PMID- 9598501
TI  - Benign prostatic hyperplasia--from bench to bedside.

PMID- 9598502
TI  - Racial differences in clinically localized prostate cancers of black and white
      men.
AB  - PURPOSE: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and
      bcl-2 expression were examined in clinically localized prostate cancers of black
      and white American men to learn whether these features showed racial differences.
      MATERIALS AND METHODS: A total of 117 prostate cancers (43 black and 74 white
      patients) obtained at radical prostatectomy for clinically localized disease were
      assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei
      from archival prostate cancers were examined by DNA flow cytometry using
      propidium iodide staining and the multicycle program to remove debris and sliced
      nuclei and to perform cell cycle analysis. For immunostaining after microwave
      antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and
      the clone 124 antibody for bcl-2. RESULTS: Significantly more black than white
      men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less
      tumors was similar for both races. As anticipated, the ploidy distribution of
      higher grade prostate cancer in white men was more abnormal but, unexpectedly,
      this was not found for higher grade prostate cancer in black men. No significant
      racial differences were found in S phase fractions, p53 or bcl-2
      immunopositivity. However, for prostate cancer in black men there was a
      significant association between bcl-2 immunopositivity and higher S-phase
      fractions. CONCLUSIONS: The aggressive prostate cancers of black men may be
      characterized by the 2 features of high proliferation and a block to programmed
      cell death.

PMID- 9598503
TI  - The epidemiology of prostate cancer in Jamaica.
AB  - PURPOSE: Before this study, the highest reported incidence of prostate cancer in
      the world was thought to be among United States black men. The age adjusted rates
      in 1992 for United States black and white men were 249 and 182/100,000
      respectively. The epidemiology of prostate cancer in Jamaica, a country of 2.5
      million people of primarily African descent, was studied and compared with that
      of white and black Americans. MATERIALS AND METHODS: The study included 1,121
      cases of prostate cancer diagnosed from 1989 to 1994. Sources of information
      included the Jamaican Cancer Registry, government pathology laboratory, hospital
      and clinic records, and physician office records. Incidence rates were computed
      using data from the 1991 Jamaican census. Age adjustments were made using the
      1970 United States standard population. RESULTS: The average age adjusted
      incidence of prostate cancer in Kingston, Jamaica was 304/100,000 men. Median
      patient age at diagnosis was 72 years. More than 80% of the cases were
      pathologically confirmed. Of the patients 30% presented with acute urinary
      retention, 16% presented with bone metastases, 15% had gross hematuria at the
      time of diagnosis and an abnormal rectal examination suspicious for cancer was
      noted in 42%. Prostate specific antigen was measured in only 7% of cases in 1989
      but in 48% of cases by 1994. CONCLUSIONS: These data demonstrate that Jamaican
      men in Kingston have a high incidence of prostate cancer, much higher than even
      black Americans during a similar period. Furthermore, the cancers are more
      significant clinically with greater morbidity in Jamaica than in the United
      States.

PMID- 9598504
TI  - Differences in urologist and patient assessments of health related quality of
      life in men with prostate cancer: results of the CaPSURE database.
AB  - PURPOSE: We determine whether urologists caring for men with prostate cancer
      accurately captured the nuances of quality of life, as disclosed by patients in
      validated, self-administered health related quality of life instruments.
      MATERIALS AND METHODS: We analyzed information on 2,252 patients 42 to 95 years
      old enrolled in CaPSURE, a large, observational cancer of the prostate strategic
      urological research endeavor database, in which men with all stages of prostate
      cancer are followed quarterly with standardized validated written surveys to
      assess clinical parameters, symptoms and health related quality of life. At each
      visit urologists recorded Karnofsky performance status rating and the presence or
      absence of various symptoms, such as fatigue, pain and dysfunction in the sexual,
      urinary and bowel domains. Within 30 days of the visit patients independently
      completed self-administered health related quality of life instruments, including
      the RAND 36-Item Health Survey and University of California, Los Angeles Prostate
      Cancer Index, in which scores of 80 to 100 and 0 to 79 were interpreted as
      absence of impairment and moderate to severe impairment, respectively. Using chi
      square analysis we compared symptoms, as recorded by the urologist, with health
      related quality of life impairment in relevant domains, as reported by the
      patient. RESULTS: Significant differences (p < or = 0.002) were noted between
      physician and patient assessment of clinical domains, such as physical, sexual,
      urinary and bowel function, fatigue and bone pain. In all domains urologists
      underestimated patient symptoms, causing health related quality of life
      impairment. CONCLUSIONS: In men with early stage and advanced prostate cancer
      physician ratings of patient symptoms do not correlate well with patient self
      assessments of health related quality of life. Hence, urologists should attempt
      to elucidate more completely the components of patient quality of life after the
      diagnosis and treatment of prostate cancer.

PMID- 9598505
TI  - Androgen deprivation therapy for asymptomatic advanced prostate cancer in the
      prostate specific antigen era: a national survey of urologist beliefs and
      practices.
AB  - PURPOSE: The use of androgen deprivation for prostate cancer without symptomatic
      metastases to the skeleton is controversial. However, by 1995 the use of medical
      androgen deprivation by injection was the thirteenth largest category of
      physician reimbursement by Medicare. To what degree do urologist attitudes
      towards androgen deprivation account for this growth? MATERIALS AND METHODS: A
      survey was mailed to 582 United States urologists practicing at least 20 hours
      per week in 1995 which asked about use of androgen deprivation therapy when
      prostate specific antigen (PSA) levels rise after primary therapy (surgery or
      radiation). They were also asked whether they believed androgen deprivation
      provided a survival benefit for patients with asymptomatic stages C and D
      disease. RESULTS: The response rate was 68%. Of the respondents 68% reported that
      they recommend androgen deprivation at least half of the time for men whose PSA
      is newly or persistently elevated following radical prostatectomy. Most (81%)
      urologists who believe that androgen deprivation offers a survival benefit for
      stage C disease said they prescribed it but more than half (53%) who do not
      believe in the efficacy of this treatment also said they still prescribe it.
      CONCLUSIONS: Many urologists maintain an inclination to prescribe androgen
      deprivation for a rising or elevated PSA despite the absence of information about
      the benefit of this approach and their own conflicting beliefs.

PMID- 9598506
TI  - Calculating prostate cancer volume preoperatively: the D'Amico equation and some
      other observations.
AB  - PURPOSE: The primary morphological determinants of cancer progression in the
      prostate are tumor volume and the percentage of Gleason grades 4 and/or 5
      disease. To date the best estimate of cancer volume before therapy has been serum
      prostate specific antigen (PSA) with Pearson's correlation coefficient value of
      approximately 0.5. Recently it was reported that prostate cancer volume
      calculated according to the formula, cancer specific serum PSA/amount of PSA
      leaking into the serum per cm.3 of cancer, highly correlates with actual cancer
      volume (R = 0.98). Because there is a definite need for greater accuracy in
      estimating cancer volume before therapy, we attempt to confirm this proposed
      equation in our radical prostatectomy series. MATERIALS AND METHODS: We applied
      this equation to the initial 318 men with peripheral zone cancer treated only
      with radical prostatectomy at our institution who were followed for a mean and
      median of greater than 5 years. Calculated prostate cancer volume was determined
      according to the aforementioned equation with minor modifications, and correlated
      with the actual cancer volume measured in radical prostatectomy specimens.
      Pearson's correlation coefficient and the coefficient of determination were
      calculated using a linear regression model. Calculated prostate cancer volume was
      also previously used to predict pathological stage pT3. We compared calculated
      prostate cancer volume, clinical stage, Gleason grade and preoperative serum PSA
      in logistic univariate and multivariate regressions to predict stage pT3 disease.
      RESULTS: Overall correlations for calculated prostate cancer volume were R =
      0.537 and R2 = 0.289 (p <0.0001), which are much less than those previously noted
      (R = 0.98 and R2 = 0.96). As in the original report, we also divided our 318
      cases into the 4 cancer volume subgroups of 0.5 cm.3 or less, 0.5 to 2.0, 2.0 to
      4.0 and greater than 4.0 cm.3 (R = 0.251, 0.288, 0.382 and 0.462, and R2 = 0.063,
      0.083, 0.146 and 0.213 alone respectively). There was an increasing trend for
      better R and R2 values with increasing prostate cancer volume. Calculated
      prostate cancer volume was less than 0.5 cm.3 in 156 of our 318 patients (49%)
      and less than 0 in 37 (11.6%). In these cases serum PSA alone strongly correlated
      with calculated prostate cancer volume (R = 0.877 and R2 = 0.77). Univariate
      analysis demonstrated statistical significance for prediction of stage pT3
      disease, Gleason grade, clinical stage, serum PSA and calculated prostate cancer
      volume but multivariate analysis revealed statistical significance only for
      Gleason grade (p <0.0001) and clinical stage (p <0.0036). Values for PSA and
      calculated prostate cancer volume were not significant (p = 0.0640 and 0.7920,
      respectively). CONCLUSIONS: Calculated prostate cancer volume did not predict
      cancer volume in our 318 patients who underwent radical prostatectomy. While we
      are uncertain how to interpret the excellent correlation of calculated prostate
      cancer volume with PSA, we believe that this correlation strongly suggests that
      most predictive information of calculated prostate cancer volume is related to
      serum PSA. Importantly in our 318 patients serum PSA was a much stronger
      predictor of cancer volume than calculated prostate cancer volume. As expected,
      Gleason grade and clinical stage are excellent predictors of stage pT3 disease
      but not of serum PSA or calculated prostate cancer volume.

PMID- 9598507
TI  - The value of the ratio of free-to-total prostate specific antigen for staging
      purposes in previously untreated prostate cancer.
AB  - PURPOSE: We analyzed the use of the ratio of free-to-total prostate specific
      antigen (PSA), also termed percentage of free PSA, for predicting tumor stage,
      volume and grade in patients with clinically localized prostate cancer. MATERIALS
      AND METHODS: A total of 515 consecutive patients underwent further prostate
      evaluation due to elevated PSA (greater than 4.0 ng./ml.) or abnormal digital
      rectal examination. Prostate cancer was diagnosed in 307 patients (59.6%),
      including 170 (55.4%) who underwent radical retropubic prostatectomy. Data on
      pathological stage, Gleason grade, and total and Gleason grade 4 cancer volume
      were available in all patients. In the remaining 208 men (40.4%) benign prostate
      hyperplasia was diagnosed. Total and free PSA was measured in preoperative serum.
      RESULTS: Total PSA was significantly higher (p <0.0001) in the 71 men with stage
      pT3 tumors than in the 91 with pT2 disease. Eight patients had stage pT4 tumors.
      Cancer volume correlated well with advancing pathological stage (p <0.0001) and
      total PSA (p <0.0001). The free-to-total PSA ratio was not significantly
      different (p = 0.93) in stages pT2 and pT3 tumors, and it did not correlate with
      total (p = 0.71) or pure Gleason grade 4 (p = 0.94) cancer volume. However, the
      ratio of free-to-total PSA tended to decrease (p = 0.07) in tumors of increasing
      Gleason grade. CONCLUSIONS: The ratio of free-to-total PSA does not help in the
      preoperative prediction of final tumor stage and volume. However, disease grading
      may alter the free-to-total PSA ratio.

PMID- 9598508
TI  - Classification of localized untreated prostate cancer based on 791 men treated
      only with radical prostatectomy: common ground for therapeutic trials and TNM
      subgroups.
AB  - PURPOSE: We examined cancer volume, percent Gleason grade 4/5 cancer, cancer
      location (peripheral versus transition zone), capsular penetration and
      biochemical cure rates in men undergoing radical prostatectomy to determine
      differences among clinical stages T1c, T2a, T2b and T2c. MATERIALS AND METHODS:
      Detailed chart reviews confirmed the precise clinical stages assigned to 791
      consecutive men treated only with radical prostatectomy. All prostates were
      examined prospectively by the Stanford technique of 3 mm. step sections. For
      biochemical cure rates a subset of 366 men were followed for a minimum of 5
      years. Failure was defined as prostate specific antigen Tosoh 0.07 ng./ml. or
      greater and rising. T1c was defined as impalpable cancer. RESULTS: T1c and T2a
      stages had half as much cancer volume as T2b and T2c cancers, 10 versus 25%
      Gleason grade 4/5 and half as much capsular penetration (30 versus 61%).
      Biochemical cure rates were 70 and 72% for T1c and T2a compared to 37 and 27% for
      T2b and T2c, respectively. Of T1c cancers 25% were in the transition zone
      compared to 7.9 to 9.9% of T2a to c cancers. CONCLUSIONS: T1c cancers are similar
      to T2a cancers in tumor volume and percent Gleason grade 4/5, the primary
      determinants of therapeutic failure. Minimal 5-year cure rates for T1c and T2a
      cancers are similar. Transition zone cancers are 2.5 times more common in T1c
      cancers than in palpable T2 tumors. T2a cancers like T1c cancers are highly
      favorable tumors and should be retained in TNM classifications. These data
      suggest that the 4 clinical stages of T1c to T2c can serve as a valid basis for
      comparing different therapeutic strategies.

PMID- 9598509
TI  - Hormonal treatment before radical prostatectomy: a 3-year followup.
AB  - PURPOSE: Hormonal treatment administered before radical prostatectomy has been
      shown to decrease the rate of positive surgical margins. We determine whether
      preoperative hormonal treatment has any impact on the subsequent failure rate.
      MATERIALS AND METHODS: We prospectively evaluated 122 patients with stages
      T1bNxM0 to T3aNxM0, grades 1 to 3 prostate cancer, including 64 randomly assigned
      to immediate radical retropubic prostatectomy and 58 randomly assigned to radical
      retropubic prostatectomy preceded by 3 months of pretreatment with a gonadotropin
      releasing hormone agonist. We performed intention to treat analysis on the data
      with failure defined as lymph node involvement, serum prostate specific antigen
      greater than 0.5 ng./ml., or the need for postoperative hormonal or radiation
      adjuvant treatment. RESULTS: The positive margin rate was 23.6 versus 45.5% in
      the pretreatment plus prostatectomy versus prostatectomy only groups (p = 0.016).
      There were 20 failures (34.5%) in the pretreatment plus prostatectomy subgroup
      and 26 (40.6%) in the prostatectomy only group (p = 0.48). A negative surgical
      margin was associated with a significantly lower risk of progression than a
      positive surgical margin (20.8 versus 50.0%, p = 0.0016), and progression was
      delayed by approximately 1 year after hormonal pretreatment. However, at a median
      followup of 38 months there was no difference in progression-free survival (p =
      0.57). CONCLUSIONS: Although hormonal pretreatment significantly decreased the
      positive margin rate, it did not result in any difference in progression-free
      survival when followup exceeded 3 years. Thus, our current results do not support
      the routine administration of hormonal treatment before radical prostatectomy.

PMID- 9598510
TI  - Clinicopathological characteristics of prostatic adenocarcinoma in men with
      atypical prostate needle biopsies.
AB  - PURPOSE: Atypical or nondefinitive diagnoses comprise 1.5 to 10% of all prostate
      needle biopsies and many men with atypical biopsy have carcinoma on rebiopsy. We
      characterize the clinical and pathological features of these men and the tumors,
      and compare them to those of other men who had more than 1 biopsy. MATERIALS AND
      METHODS: All prostate needle biopsies done at our institution between 1989 and
      1996 on men with a followup biopsy were reviewed and the clinicopathological
      features were correlated. RESULTS: A total of 343 men had more than 1 biopsy
      during this period. Of the biopsies 64 were atypical and followup (repeat biopsy)
      was available for 59. Men with an atypical diagnosis were more likely to have
      carcinoma (34%) and to be diagnosed subsequently earlier (270 days) than those
      with an initial negative diagnosis (22%, 603 days). No significant differences
      were noted in patient age, results of digital rectal examination, initial or
      followup serum prostate specific antigen, subsequently identified tumor size or
      Gleason score on needle biopsy or at resection. Although on review as many as 38%
      of the original atypical foci could be reclassified, this reclassification did
      not significantly change the results of rebiopsy. CONCLUSIONS: Men with an
      atypical diagnosis on prostate biopsy are significantly more likely to have
      carcinoma on rebiopsy than men with an initial negative diagnosis, and the second
      biopsy should be performed at a significantly shorter interval. The tumors that
      are subsequently identified in these men are similar to those identified in men
      without an atypical biopsy.

PMID- 9598511
TI  - Systematic sextant biopsies improve preoperative prediction of pelvic lymph node
      metastases in patients with clinically localized prostatic carcinoma.
AB  - PURPOSE: An algorithm including the results of systematic sextant biopsies was
      statistically developed and evaluated to predict the probability of pelvic lymph
      node metastases in patients with clinically localized carcinoma of the prostate.
      MATERIALS AND METHODS: Clinical stage, serum prostate specific antigen
      concentration, Gleason score, number of positive biopsies, number of biopsies
      containing any Gleason grade 4 or 5 cancer and number of biopsies predominated by
      Gleason grade 4 or 5 cancer were recorded in 345 patients undergoing pelvic lymph
      node dissection and correlated with the incidence of lymph node metastases.
      Multivariate logistic regression, and classification and regression trees
      analyses were performed. RESULTS: In univariate analysis all variables had a
      statistically significant influence on lymph node status. Logistic regression
      showed that the amount and distribution of undifferentiated Gleason grade 4 and 5
      cancer in the biopsies were the best predictors of lymphatic spread followed by
      serum prostate specific antigen. Classification and regression trees analysis
      classified 79.9% of patients who had 3 or fewer biopsies with Gleason grade 4 or
      5 cancer and no biopsies predominated by undifferentiated cancer as a low risk
      group. In this group positive lymph nodes occurred in only 2.2% (95% confidence
      interval 0.8 to 4.7%). CONCLUSIONS: Including the results of systematic sextant
      biopsies substantially enhances the predictive accuracy of algorithms that define
      the probability of lymph node metastases in prostatic cancer. Patients thus
      defined as having no lymphatic spread could potentially be spared pelvic lymph
      node dissection before definitive local treatment.

PMID- 9598512
TI  - Combined orchiectomy and external radiotherapy versus radiotherapy alone for
      nonmetastatic prostate cancer with or without pelvic lymph node involvement: a
      prospective randomized study.
AB  - PURPOSE: We compare the combination of orchiectomy and radiotherapy to
      radiotherapy alone as treatment for pelvic confined prostate cancer, that is T1
      4, pN0-3, M0 (TNM classification). MATERIALS AND METHODS: In this prospective
      study 91 patients with clinically localized prostate cancer were, after surgical
      lymph node staging, randomized to receive definitive external beam radiotherapy
      (46) or combined orchiectomy and radiotherapy (45). Patients treated with
      radiotherapy alone had androgen ablation at clinical disease progression. The
      effects on progression-free, disease specific and overall survival rates were
      calculated. RESULTS: After a median followup of 9.3 years (range 6.0 to 11.4)
      clinical progression was seen in 61% of the radiotherapy only patients (group 1)
      and in 31% of the combined treatment patients (group 2) (p = 0.005). The
      mortality was 61 and 38% (p = 0.02), and cause specific mortality was 44 and 27%,
      respectively (p = 0.06), in groups 1 and 2. The differences in favor of combined
      treatment were mainly caused by lymph node positive tumors. For node negative
      tumors there was no significant difference in survival rates. CONCLUSIONS: The
      progression-free, disease specific and overall survival rates for patients with
      prostate cancer and pelvic lymph node involvement are significantly better after
      combined androgen ablation and radiotherapy than after radiotherapy alone. These
      results strongly suggest that early androgen deprivation is better than deferred
      endocrine treatment for these patients.

PMID- 9598513
TI  - Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3
      (calcitriol)
AB  - PURPOSE: Substantial experimental and epidemiological data indicate that 1,25
      dihydroxyvitamin D3 (calcitriol) has potent antiproliferative effects on human
      prostate cancer cells. We performed an open label, nonrandomized pilot trial to
      determine whether calcitriol therapy is safe and efficacious for early recurrent
      prostate cancer. Our hypothesis was that calcitriol therapy slows the rate of
      rise of prostate specific antigen (PSA) compared with the pretreatment rate.
      MATERIALS AND METHODS: After primary treatment with radiation or surgery
      recurrence was indicated by rising serum PSA levels documented on at least 3
      occasions. Seven subjects completed 6 to 15 months of calcitriol therapy,
      starting with 0.5 microg. calcitriol daily and slowly increasing to a maximum
      dose of 2.5 microg. daily depending on individual calciuric and calcemic
      responses. Each subject served as his own control, comparing the rate of PSA rise
      before and after calcitriol treatment. RESULTS: As determined by multiple
      regression analysis, the rate of PSA rise during versus before calcitriol therapy
      significantly decreased in 6 of 7 patients, while in the remaining man a
      deceleration in the rate of PSA rise did not reach statistical significance.
      Overall the decreased rate of PSA rise was statistically significant (p = 0.02
      Wilcoxon signed rank test). Dose dependent hypercalciuria limited the maximal
      calcitriol therapy given (range 1.5 to 2.5 microg. daily). CONCLUSIONS: This
      pilot study provides preliminary evidence that calcitriol effectively slows the
      rate of PSA rise in select cases, although dose dependent calciuric side effects
      limit its clinical usefulness. The development of calcitriol analogues with
      decreased calcemic side effects is promising, since such analogues may be even
      more effective for treating prostate cancer.

PMID- 9598514
TI  - 111Indium-capromab pendetide in the evaluation of patients with residual or
      recurrent prostate cancer after radical prostatectomy. The ProstaScint Study
      Group.
AB  - PURPOSE: Standard diagnostic methods are limited for detecting distant metastases
      in patients with prostate cancer in whom the only evidence of disease after
      radical prostatectomy is a detectable prostate specific antigen (PSA) level. We
      evaluated the role of immunoscintigraphy with the radiolabeled monoclonal
      antibody, 111indium ((111)In)-capromab pendetide, to differentiate between local
      and distant recurrence in this patient population. MATERIALS AND METHODS: We
      enrolled 183 men who had undergone radical prostatectomy in whom PSA later
      increased. Gamma camera images were acquired twice after infusion of a single
      dose of (111)In-capromab pendetide. RESULTS: Immunoscintigraphy revealed disease
      in 108 of 181 patients (60%) with interpretable scans. The antibody was localized
      most frequently to the prostatic fossa (34% of the cases), abdominal lymph nodes
      (23%) and pelvic lymph nodes (22%). Of the 181 men the scan localized the
      antibody outside the prostatic fossa in 42%. Half of the positive localizations
      in the fossa were confirmed by biopsy. CONCLUSIONS: These findings suggest that
      immunoscintigraphy with (111)In-capromab pendetide can assist in determining the
      extent of disease in patients who have increasing PSA after prostatectomy.

PMID- 9598515
TI  - Transurethral resection of partially obstructed ejaculatory ducts: seminal
      parameters and pregnancy outcomes according to the etiology of obstruction.
AB  - PURPOSE: We determine how transurethral resection of the ejaculatory ducts
      performed for infertility affects seminal parameters and pregnancy outcomes in
      patients with partial ejaculatory duct obstruction due to a congenital or
      acquired etiological factor. MATERIALS AND METHODS: Based on history and physical
      examination, hormonal profiles, semen analyses, transrectal ultrasonography and
      vasography findings partial ejaculatory duct obstruction was diagnosed in 14 men
      a mean of 30 years old who presented for infertility evaluation. Patients were
      grouped according to congenital or acquired cause of obstruction. Transurethral
      resection of the ejaculatory ducts was performed using the standard resectoscope
      loop technique. Clinical outcome was assessed by postoperative analyses of
      seminal parameters and pregnancy reports. RESULTS: Transurethral resection of the
      ejaculatory ducts significantly improved semen quality (ejaculate volume and
      percentage of sperm motility) in all patients in the congenital group, while all
      but 1 (83%) had an improved sperm count. Pregnancy was achieved via sexual
      intercourse by 66% of the patients an average of 5.7 months postoperatively. Of
      the acquired etiological factor group 37.5% had improved semen quality after
      transurethral resection of ejaculatory duct and 12.5% achieved pregnancy via
      sexual intercourse. Postoperative complications occurred at a similar rate in
      each group (33%). However, complications in the congenital etiology group were
      minor, while 25% of the men in the acquired group had significant impairment of
      seminal parameters after transurethral resection of the ejaculatory ducts.
      CONCLUSIONS: Semen quality improvement and pregnancy outcome after transurethral
      resection of the ejaculatory ducts for partial ejaculatory duct obstruction
      differ significantly according to the main etiological cause of obstruction. An
      equivocal diagnosis of partial obstruction and technical problems during
      transurethral resection of the ejaculatory ducts may contribute to failure.
      However, in some cases the reason for failure remains unclear.

PMID- 9598516
TI  - Strain relatedness in persistent and recurrent candiduria.
AB  - PURPOSE: We assessed the value of determining strain relatedness in
      differentiating persistent from recurrent candiduria. MATERIALS AND METHODS:
      Prospective monitoring of patients with candiduria (10(4) or greater colony
      forming units per ml.) during a 5-month period. All patients with persistent or
      recurrent infection after documented clearance were selected. Pair isolates were
      typed using restriction endonuclease analysis of genomic deoxyribonucleic acid
      with SfiI. Isolates were considered related if all deoxyribonucleic acid bands
      matched. RESULTS: We encountered 22 and 5 patients with persistent and recurrent
      infection, respectively. The isolates were recovered 1 to 140 days apart (21.56
      +/- 28.97). Most patients were women (85.2%) with a mean age of 66.41 +/- 18.11
      years. Risk factors included antibiotics (100%), indwelling catheter (88.9%) and
      diabetes mellitus (40.7%). Of 15 individuals who received antifungal therapy
      candiduria persisted in 10 and resolved but recurred within 4 to 26 days (13.00
      +/- 9.08) after treatment in 5. Candida albicans accounted for 34 of 58 isolates
      (58.6%), and it was mixed with other species in 4 cultures. Paired strains were
      genetically identical in 26 of 27 patients. Strain persistence was documented in
      21 of 22 cases with persistent infection and in all 5 patients with recurrent
      disease. CONCLUSIONS: These findings show that strain persistence is exceedingly
      frequent in candiduria. These results imply that determining strain relatedness
      of Candida urinary isolates may not be reliable in differentiating persistent
      from recurrent infection.

PMID- 9598517
TI  - Urodynamic factors influence the duration of Escherichia coli bacteriuria in
      deliberately colonized cases.
AB  - PURPOSE: We evaluated the influence of urodynamic factors on the establishment of
      bacteriuria, after deliberate intravesical inoculation with Escherichia coli.
      MATERIALS AND METHODS: Nine women and 7 men with recurrent symptomatic urinary
      tract infections underwent intravesical injection of E. coli 83972. This strain
      had documented ability to persist in the urinary tract and it lacks expressed
      virulence factors associated with urinary tract infection. RESULTS: Successful
      long-term colonization (5 months to 3 years) was achieved in 6 of 12 patients
      with neurogenic bladder disorder, including normal or high bladder capacity,
      normal or low detrusor pressure and residual urine. Short-term bacteriuria (13
      days) occurred in 1 but long-term bacteriuria was not established in the 4
      patients with normal lower urinary tract function. Occasionally urine samples
      from the colonized patients contained other bacterial strains, which cleared
      spontaneously except for a Klebsiella strain that became established in 2 and
      subsequently eliminated E. coli 83972. CONCLUSIONS: E. coli 83972 bacteriuria
      could only be established in a subset of patients with defective bladder voiding,
      suggesting that urodynamic defects permit a nonvirulent strain to establish in
      the urinary tract, but that additional host factors determine if bacteriuria will
      persist.

PMID- 9598518
TI  - Use of the harmonic scalpel for nephron sparing surgery in renal cell carcinoma.
AB  - PURPOSE: The harmonic scalpel is a new tool for excising and coagulating tissue
      with ultrasound using higher frequencies than an ultrasonic aspirator. We
      evaluated the usefulness of the harmonic scalpel in nephron sparing surgery.
      MATERIALS AND METHODS: We used the harmonic scalpel to incise the renal
      parenchyma during nephron sparing surgery in 10 patients with renal cell
      carcinoma. RESULTS: Bleeding from the renal parenchyma was minimal but hemostasis
      of the larger vessels was not obtained even when the harmonic scalpel was used at
      maximal coagulation power. The cut surface of the kidneys, especially the
      vessels, were more clearly recognized than if an ultrasonic aspirator had been
      used, enabling hemostasis by figure-of-8 suture. CONCLUSIONS: The harmonic
      scalpel is useful for obtaining a clear parenchymal stump and hemostasis during
      nephron sparing surgery, although complete hemostasis of the arcuate or larger
      vessels cannot be achieved.

PMID- 9598519
TI  - Knotted ureteral stent: a minimally invasive technique for removal.
AB  - PURPOSE: We describe a useful technique for untying a knotted ureteral catheter.
      MATERIALS AND METHODS: An Amplatz super stiff guide wire was advanced through the
      lumen of the stent and with uniform force the knot was untied. RESULTS: The knot
      was untied and the stent was removed. A nephrostomy tube or other more invasive
      techniques for removal were avoided. CONCLUSIONS: An Amplatz super stiff guide
      wire passed retrograde via the ureteral stent lumen should be considered as a
      valid alternative to percutaneous removal of a knotted ureteral stent.

PMID- 9598520
TI  - Evaluation of new resectoscope loop for transurethral resection of bladder
      tumors.
AB  - PURPOSE: We evaluate a new resectoscope loop for transurethral resection of
      bladder tumors. MATERIALS AND METHODS: Of 251 transurethral resections in 226
      patients 111 were done with a conventional loop and 140 with the Olympus
      prototype model A2186 resectoscope loop. The quality of specimens provided for
      histological analysis was compared. RESULTS: Tissue orientation was preserved and
      cautery artifact was reduced with the new loop compared to the standard
      resectoscope loop. CONCLUSIONS: Compared to a conventional resectoscope loop, the
      new loop resulted in a better tumor resection and helped facilitate histological
      evaluation of the tissue specimens.

PMID- 9598521
TI  - In vivo endoscopy of the seminal vesicle.

PMID- 9598522
TI  - Small bowel and splenic injury during percutaneous renal surgery.

PMID- 9598523
TI  - Nephrolithiasis from indinavir, a new human immunodeficiency virus drug.

PMID- 9598524
TI  - Renal botryomycosis mimicking renal cell carcinoma.

PMID- 9598525
TI  - Erythema gyratum repens in association with renal cell carcinoma.

PMID- 9598526
TI  - Renal cell carcinoma presenting with mesenteric thrombosis and anticardiolipin
      antibodies: echoes of Trousseau's syndrome?

PMID- 9598527
TI  - Ureteropelvic junction obstruction in an endothoracic kidney: successful
      treatment with retrograde balloon divulsion and stenting.

PMID- 9598528
TI  - Endourological management of a large distal ureteral calculus in a patient with
      ureterosigmoidostomy diversion.

PMID- 9598529
TI  - Treatment of a ureteroiliac artery fistula with an intraluminal endovascular
      graft.

PMID- 9598530
TI  - Retrovesical hydatid cyst.

PMID- 9598531
TI  - Retroperitoneal hematoma due to rupture of a pseudoaneurysm caused by acupuncture
      therapy.

PMID- 9598532
TI  - Spontaneous extraperitoneal bladder rupture.

PMID- 9598533
TI  - Tuberculous enteritis after intravesical bacillus Calmette-Guerin therapy: a case
      of mistaken identity.

PMID- 9598534
TI  - Factor V Leiden presenting with penile vein thrombosis.

PMID- 9598535
TI  - Penile fracture after intracavernous injection therapy.

PMID- 9598536
TI  - Development of testicular seminoma after previous negative biopsy for testicular
      intraepithelial neoplasia.

PMID- 9598537
TI  - Dermatomyositis associated with intratubular germ cell tumor and metastatic germ
      cell cancer.

PMID- 9598538
TI  - Flutamide induced lupus.

PMID- 9598539
TI  - Interstitial pneumonitis associated with neoadjuvant leuprolide and nilutamide
      for prostate cancer.

PMID- 9598540
TI  - Prolonged survival with metastatic prostate cancer to bone.

PMID- 9598541
TI  - Re: The psychosocial impact of donating a kidney: long-term followup from a
      urology based center.

PMID- 9598542
TI  - Re: Long-term results of percutaneous endopyelotomy in the treatment of children
      with failed open pyeloplasty.

PMID- 9598543
TI  - Re: Diagnosis and management of ureteroiliac artery fistula: value of provocative
      arteriography followed by common iliac artery embolization and extraanatomic
      arterial bypass grafting.

PMID- 9598544
TI  - Re: Contralateral vesicoureteral reflux after simple and tapered unilateral
      ureteroneocystostomy revisited.

PMID- 9598545
TI  - Re: Inguinal scrotal incision for penile fracture.

PMID- 9598546
TI  - Re: The relationship of sperm counts to birth rates: a population based study.

PMID- 9598547
TI  - Re: Somatosensory evoked potentials in patients with primary premature
      ejaculation.

PMID- 9598548
TI  - Re: Prognostic implications of a positive apical margin in radical prostatectomy
      specimens.

PMID- 9598549
TI  - Re: Immediate versus deferred treatment for advanced prostate cancer: initial
      results of the medical research council trial.

PMID- 9598550
TI  - Negative effect of vascular shunt on renal autotransplant in conjoined twins is
      reversible after separation.

PMID- 9598551
TI  - Renal transplantation in children with augmentation cystoplasty: long-term
      results.
AB  - PURPOSE: We assessed the long-term results of renal transplantation in children
      with augmentation cystoplasty. MATERIALS AND METHODS: We retrospectively reviewed
      the complications and followup in 14 pediatric renal transplant recipients with
      augmentation cystoplasty. The etiology of bladder dysfunction included posterior
      urethral valves in 10 cases, neurogenic bladder in 3 and vesicoureteral reflux in
      1. All transplants were cadaver donor kidneys. Mean patient age at
      transplantation was 12.1 years (range 5 to 18). Augmentation cystoplasty was
      performed before and after transplantation in 10 and 4 cases, respectively.
      Detubularized ileum was used in 5 cases, tubular ileum in 4, tubular sigmoid in 4
      and stomach in 1. RESULTS: Of the 14 transplanted kidneys 10 (71%) were
      functioning at a mean followup of 80 months (range 12 to 151). Serum creatinine
      was less than 1.4 mg./dl. in 9 patients. Four grafts were lost to chronic
      rejection. The 5 and 10-year graft survival rates were 84 and 73%, respectively.
      Two patients with a functioning kidney died of causes unrelated to augmentation
      cystoplasty. Complications included symptomatic urinary infections in 4 patients,
      hyperchloremic metabolic acidosis in 2, nephrolithiasis in the allograft in 2 and
      the hematuria-dysuria syndrome in 1. All patients were continent. CONCLUSIONS:
      Augmentation cystoplasty is a safe and effective method of restoring lower
      urinary tract function in the pediatric renal transplant population with a small
      noncompliant bladder.

PMID- 9598552
TI  - Giant hyperplastic nephrogenic rest in a solitary kidney presenting as an
      angiomyolipoma in a child.

PMID- 9598553
TI  - Outcome based comparison of surgical approaches for pediatric pyeloplasty: dorsal
      lumbar versus flank incision.
AB  - PURPOSE: Dismembered pyeloplasty for the correction of ureteropelvic junction
      obstruction can be performed through a flank or dorsal lumbar incision. We
      compared the records of children who had undergone pyeloplasty by each approach
      to determine if 1 technique was more advantageous. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 33 consecutive children undergoing simple
      dismembered pyeloplasty by a single pediatric urologist from 1992 to 1996. The
      flank approach was used exclusively in the first group of patients who underwent
      repair in 1992 to 1993 and the dorsal lumbar incision was used exclusively in the
      second group after 1993. Data were obtained from hospital and clinic records, and
      both groups were compared with the 2-tailed t test. RESULTS: Pyeloplasty was done
      by dorsal lumbar incision in 16 cases and via the flank approach in 17. One
      patient in each group had undergone simultaneous bilateral pyeloplasties.
      Although overall comparison of both groups revealed no differences in operative
      time, in children older than 1 year pyeloplasty through a dorsal lumbar incision
      (108.5 minutes) was statistically significantly faster than the flank approach
      (144.4 minutes). Hospital stay was approximately 2 days shorter in infants who
      had a dorsal lumbar (25.7 hours) versus a flank incision (73 hours), and this
      difference did reach statistical significance if the bilateral pyeloplasty
      patients were excluded. Hospital costs were less for the dorsal lumbar group but
      the difference was not statistically significant. Success and complication rates
      were similar between groups with 2 patients in each group requiring additional
      procedures. Review of other series of repair of ureteropelvic junction
      obstruction demonstrated that the dorsal lumbar repair had equivalent or shorter
      operative times and lengths of hospitalization compared to newer endoscopic
      methods, and the outcomes were superior. CONCLUSIONS: The dorsal lumbar incision
      is a safe and efficacious approach to pyeloplasty and may be more cost-effective.
      In our series it was significantly faster in patients older than 1 year and
      resulted in shorter hospital stays in those younger than 1 year old.

PMID- 9598554
TI  - Duplex kidney, Gartner's duct cyst and ipsilateral Mullerian duct obstruction.

PMID- 9598555
TI  - Epidermolysis bullosa: a review of the associated urological complications.
AB  - PURPOSE: Epidermolysis bullosa is a devastating rare disorder that rarely
      presents with urological complications. We report our experience with and review
      the literature on this disorder. MATERIALS AND METHODS: Two brothers with
      epidermolysis bullosa presented to our center with severe dysuria and urinary
      tract obstruction caused by meatal stenosis. The obstruction was temporarily
      relieved by meatotomy but recurrent obstructive skin blistering with severe
      dysuria required ureterosigmoidostomy for palliation of symptoms. RESULTS: Both
      children tolerated ureterosigmoidostomy well with 1 requiring bicarbonate
      supplementation for metabolic acidosis. Ureterosigmoidostomy greatly improved
      quality of life, and both children have complete symptom relief. CONCLUSIONS:
      Epidermolysis bullosa is usually a severe illness associated with a poor
      prognosis. Crippling urological symptoms may develop due to recurrent skin
      blistering causing severe dysuria and secondary obstruction.
      Ureterosigmoidostomy, despite its complications, provides significant palliation
      for patients with recalcitrant symptoms.

PMID- 9598556
TI  - Incidence of contralateral vesicoureteral reflux following unilateral
      extravesical detrusorrhaphy (ureteroneocystostomy).
AB  - PURPOSE: The development of contralateral vesicoureteral reflux following
      different types of unilateral antireflux surgery has been reported to be as high
      as 22%. We review our recent experience with unilateral extravesical
      detrusorrhaphy in regard to the incidence of postoperative contralateral
      vesicoureteral reflux. MATERIALS AND METHODS: Between 1990 and 1995, 72 children
      underwent unilateral extravesical detrusorrhaphy. Of 73 refluxing renal moieties
      (1 patient had reflux in both moieties of a completely duplicated kidney) reflux
      grade was II in 35 (48%), III in 25 (34%), IV in 11 (15%) and V in 2 (3%). Common
      sheath reimplantation for complete ipsilateral duplication was performed in 16
      patients. RESULTS: One patient had grade I postoperative ipsilateral
      vesicoureteral reflux resulting in a success rate of 98.6%. In 4 patients (5.6%)
      contralateral vesicoureteral reflux developed, and was grade II in 3 and grade I
      in 1. In all patients contralateral reflux resolved at 16, 17, 18 and 31 months
      of followup. No additional surgery was required in any patient. There was no
      association between the incidence of contralateral vesicoureteral reflux, and
      patient age, gender, preoperative ipsilateral reflux grade and presence of
      ipsilateral duplication. CONCLUSIONS: Unilateral extravesical detrusorrhaphy is a
      highly successful procedure with a low incidence of postoperative contralateral
      vesicoureteral reflux. Should reflux develop, it is of low grade with a
      significant rate of spontaneous resolution.

PMID- 9598557
TI  - Tubularized incised plate hypospadias repair for proximal hypospadias.
AB  - PURPOSE: We report a multicenter experience using tubularized incised plate
      urethroplasty for proximal hypospadias. MATERIALS AND METHODS: From August 1993
      to December 1996 tubularized incised plate urethroplasty was performed in 27 boys
      6 months to 3 years old with mid shaft and penoscrotal hypospadias. In 7 other
      boys complex reconstruction combined the tubularized incised plate technique for
      the glanular urethra with other repairs for the proximal urethra. RESULTS:
      Tubularized incised plate surgery created a functional neourethra even in
      penoscrotal hypospadias. Complications of the primary repair developed in only 3
      of 27 patients (11%). No complications were attributed to use of the technique
      for the glanular urethra in complex repairs. CONCLUSIONS: Tubularized incised
      plate urethroplasty is a versatile operation that corrects proximal hypospadias
      defects with few complications and superior cosmetic results.

PMID- 9598558
TI  - Laparoscopic orchiopexy: procedure of choice for the nonpalpable testis?
AB  - PURPOSE: Multiple approaches exist for the management of the nonpalpable testis.
      With the use of diagnostic laparoscopy widely accepted in the setting of the
      nonpalpable testis we have found laparoscopic orchiopexy to be an efficient and
      logical extension. To evaluate its use we report our experience with laparoscopic
      orchiopexy to treat 44 nonpalpable testes in 36 patients. MATERIALS AND METHODS:
      We retrospectively reviewed the medical records of all patients who underwent
      laparoscopic orchiopexy for a 2 1/2-year period. Modifications of the surgical
      technique are described. RESULTS: The left testis was affected in 18 boys, the
      right in 9 and both in 9. At laparoscopy 8 testes were at the internal ring or
      were peeping and the remainder were intra-abdominal. One patient underwent a
      unilateral 1-stage Fowler-Stephens orchiopexy, and 3 unilateral and 1 bilateral 2
      stage Fowler-Stephens orchiopexy. Two patients underwent laparoscopically
      assisted orchiectomy. The remaining 31 patients underwent laparoscopic orchiopexy
      without division of the spermatic vessels. At followup (mean 6 months) all testes
      are without atrophy, and 39 of 42 (93%) are in an acceptable scrotal position.
      There are 3 testes (7%) high in the scrotum. CONCLUSIONS: Laparoscopic orchiopexy
      is a logical extension of diagnostic laparoscopy for the evaluation and treatment
      of the nonpalpable testis. The low incidence of complications and 93% success
      rate underscore the feasibility of this procedure. It is our procedure of choice
      for the treatment of nonpalpable testis.

PMID- 9598559
TI  - Surfactant administration reduces testicular ischemia-reperfusion injury.
AB  - PURPOSE: The mechanism of testicular ischemia-reperfusion injury has not been
      well delineated. We determined the efficacy of a biocompatible surfactant
      (tetronic 1107) to reduce tissue injury and evaluated cell membrane integrity as
      reflected by calcium ion permeability in an in vivo animal model of testicular
      ischemia-reperfusion. MATERIALS AND METHODS: Three groups of male Sprague-Dawley
      rats (6 per group) were studied. Group 1 was the nonoperative control, and groups
      2 and 3 underwent 4 hours of unilateral testicular ischemia followed by 4 hours
      of reperfusion. Ten minutes after reperfusion 0.4 ml. saline was administered
      intravenously to group 2 and 180 mg./kg. surfactant tetronic 1107 to group 3.
      99mTechnetium pyrophosphate was used to monitor calcium ion uptake by the
      ipsilateral and contralateral testicles. Both testicles were also examined
      histologically. RESULTS: The surfactant treated animals had markedly diminished
      hemorrhagic discoloration and vascular congestion compared to saline treated
      animals. These results were confirmed microscopically with improved nuclear
      chromicity and disarray of germ cell layers of the seminiferous tubules. The
      surfactant treated group also had a statistically significant (p <0.05) reduction
      in radiotracer uptake compared to the saline treated animals, confirming a
      reduction in calcium ion permeability. CONCLUSIONS: The results of this study
      suggest that tetronic 1107 is effective in reducing tissue damage in a testicular
      ischemia-reperfusion animal model.

PMID- 9598560
TI  - Perineal reconstruction in girls with high vaginal atresia.
AB  - PURPOSE: We present a novel surgical treatment for secondary hematocolpos in
      adolescent girls with high vaginal atresia. MATERIALS AND METHODS: Vaginoplasty
      was performed in 5 girls 12 to 14 years old with high vaginal atresia. The
      operation included the perineal approach, mobilization of hematocolpos and
      plastic surgery of the distal portion of the vagina using a U-shaped mucous
      submucous vaginal flap, and introital and labial flaps. RESULTS: There were no
      complications 4 to 6 months after the operation. There were no instances of
      cosmetic defects and stenosis. CONCLUSIONS: The proposed technique reduces the
      difficulty and trauma of the operation for high vaginal atresia with hematocolpos
      and an absent distal portion of the vagina. An increase in plastic reserve
      provided by the original mobilization of hematocolpos and U-shaped vaginal flap
      makes intestinal and skin colpopoiesis unnecessary.

PMID- 9598561
TI  - Anatomy of radical prostatectomy as defined by magnetic resonance imaging.
AB  - PURPOSE: We examined and defined anatomical structures relevant to radical
      prostatectomy using magnetic resonance imaging. MATERIALS AND METHODS: Before
      radical prostatectomy, 15 men underwent high-resolution magnetic resonance
      imaging studies of their pelvic floors (fast spin echo, T2 weighting of 3- to 4
      mm. contiguous or overlapping slices) in axial, coronal, and sagittal planes.
      RESULTS: Pubovesical ligaments, rather than the commonly reported puboprostatic
      ligaments, were observed attaching the bladder-prostate unit to the pubis. We
      suggest that the part of the urethra that extends from the apex of the prostate
      to the bulb of the penis, which is surrounded by the striated sphincter, should
      be termed the sphincteric urethra rather than the membranous urethra. Further, we
      found no evidence that supports the traditional concept of a urogenital
      diaphragm. The lower part of the striated urethral sphincter was flanked on its
      sides by the anterior recesses of the ischioanal fossae. The portion of the
      levator ani, which we have termed the puboanalis sling, flanked the apex of the
      prostate. The most anteromedial portion of this sling inserts into the perineal
      body and should be termed the puboperinealis. The terminal part of the
      gastrointestinal tract (the part continued beyond the levator ani) should be
      termed the anal canal, not the rectum, as used frequently in the urologic
      literature. Therefore, the initial plane of dissection in radical perineal
      prostatectomy passes along the anterior portion of the anal canal, not the
      rectum. CONCLUSION: We used magnetic resonance imaging to study male pelvic floor
      and perineal anatomy without the artifact of dissection. This study allowed us to
      devise a more precise nomenclature with respect to radical prostatectomy and, in
      so doing, to provide a better understanding of both the retropubic and the
      perineal operations.

PMID- 9598562
TI  - Preliminary results comparing the recovery of basic fibroblast growth factor (FGF
      2) in adipose tissue and benign and malignant renal tissue.
AB  - PURPOSE: Basic fibroblast growth factor (bFGF or FGF-2) is mitogenic to numerous
      epithelial, mesodermal and endothelial cells, and thus may play a role in the
      neovascularity and progression of several tumors. Furthermore, FGF-2 is reported
      to be elevated in the serum and urine of patients with various cancers, including
      renal cancer. Obesity, with increased body fat, is a risk factor for renal cancer
      through unknown mechanisms. Since adipose tissue is a source of FGF-2, we
      determined the quantity and quality of activity of FGF-2 in omental adipose
      tissue and compared it to normal and cancerous renal tissue. MATERIALS AND
      METHODS: Using heparin-Sepharose chromatography we extracted proteins from human
      omental adipose tissue, renal cell carcinoma (RCC) and benign renal tissue (BRT).
      Using FGF-2 antisera we performed western blot analysis to confirm their homology
      to FGF-2. We also assessed recovery, mitogenicity and angiogenicity of each of
      the proteins using thymidine incorporation into human umbilical vein endothelial
      cells (HUVEC) and the chorioallantoic membrane (CAM) assay. RESULTS: Each of the
      three purified mitogenic proteins eluted with NaCl concentrations between 1.4 M.
      and 1.8 M., similar to control FGF-2. There was greater recovery of FGF-2 from
      omental adipose tissue compared with renal cell carcinoma or benign renal tissue
      (42 microg. vs. 24 microg. and 18 microg., respectively; ANOVA p <0.05).
      Moreover, FGF-2 from adipose tissue had greater mitogenic activity (96.% versus
      68% and 38%; p <0.05) and greater angiogenic activity (5.5 vessels versus 2.7 and
      1.6 vessels; p <0.05) on the CAM assay. CONCLUSIONS: We suggest that human
      omental adipose tissue FGF-2 may demonstrate greater mitogenic and angiogenic
      activity than either benign or cancerous renal tissue FGF-2. It is not known if
      FGF-2 from adipose tissue may play a role in the relationship between obesity and
      renal cancer.

PMID- 9598563
TI  - Effects of sildenafil on the relaxation of human corpus cavernosum tissue in
      vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes.
AB  - PURPOSE: Sildenafil, an inhibitor of cGMP-specific phosphodiesterase 5 (PDE5), is
      currently undergoing evaluation as an oral therapy for penile erectile
      dysfunction. The aims of this study were to investigate the mechanism of action
      of sildenafil on the neurogenic relaxation of human corpus cavernosum (HCC) in
      vitro and to determine the activity of sildenafil against a full range of PDE
      isozymes. MATERIALS AND METHODS: Strips of HCC tissue were precontracted with
      phenylephrine. Relaxation responses resulting from electrical field stimulation
      (EFS) were then determined in the presence and absence of sildenafil. The effects
      of sildenafil on PDE1 to 5 prepared from human tissues and PDE6 from bovine
      retina were determined by measuring the conversion of [3H]-cGMP or [3H]-cAMP to
      their respective [3H]-5'-mononucleotides. RESULTS: Sildenafil (0.001 to 1 microM)
      enhanced the EFS-induced, nitric oxide (NO) dependent, relaxation of HCC in a
      concentration-dependent manner to a maximum of 3 times the pretreatment level at
      1 microM sildenafil. Compared with zaprinast, an early PDE5 inhibitor, sildenafil
      was approximately 240-fold more potent, inhibiting PDE5 from HCC with a geometric
      mean IC50 of 3.5 nM. For sildenafil, IC50 values for inhibition of PDE1 to 4 were
      80 to more than 8500 times greater than that for PDE5 and the IC50 for PDE6 (33
      nM) was approximately 9-fold greater. CONCLUSIONS: The data support the proposal
      that enhancement of penile erection by sildenafil in patients with erectile
      dysfunction involves potentiation of the NO-stimulated cGMP signal mediating
      relaxation of cavernosal smooth muscle during sexual stimulation. Sildenafil is a
      potent inhibitor of PDE5 from HCC, with high selectivity for PDE5 relative to
      other PDE isozymes.

PMID- 9598564
TI  - Evidence for involvement of the subcoeruleus nucleus and nucleus raphe magnus in
      urine storage and penile erection in decerebrate rats.
AB  - PURPOSE: Micturition and male sexual activity require the lower urinary tract to
      function. During the sexual act, micturition must be inhibited and urine stored
      in the bladder. We studied the role of the brainstem in relation to both
      micturition/urine storage and penile erection in rats. MATERIALS AND METHODS:
      Wire electrodes were placed on the dorsal nerve of the penis and microelectrodes
      for stimulation were introduced into the brainstem in decerebrate male rats.
      Electrical stimulation was used to locate optimally responding sites by
      monitoring the isovolumetric intravesical pressure and intracavernous pressure.
      RESULTS: Electrical stimulation of the dorsal nerve of the penis, the
      subcoeruleus nucleus in the rostral pons, and the nucleus raphe magnus in the
      caudal pons increased intracavernous pressure, but inhibited rhythmic bladder
      contractions. Electrical stimulation of Barrington's nucleus (the pontine
      micturition center in the rat) in the rostral pons induced bladder contraction.
      Stimulation of the pontine reticular formation did not increase intracavernous
      pressure. Acute transection of the thoracic spinal cord eliminated rhythmic
      bladder contractions, but gave rise to sporadic increments of intracavernous
      pressure. CONCLUSIONS: This electrophysiological study demonstrated that the
      subcoeruleus nucleus and nucleus raphe magnus are involved in both urine storage
      and penile erection, and that their physiological functions are reciprocally
      controlled; so that erection leads to inhibition of micturition.

PMID- 9598565
TI  - The effect of (L)-cysteine and (L)-2-oxothiazolidine-4-carboxylic acid (OTZ) on
      urinary oxalate excretion: studies using a hyperoxaluric rat model.
AB  - PURPOSE: To determine the efficacy of (L)-cysteine and (L)-2-oxothiazolidine-4
      carboxylic acid (OTZ) in reducing urinary oxalate excretion under hyperoxaluric
      conditions and to determine whether by inclusion of glycolate in a standard diet,
      cysteine:glyoxylate adduct can be detected in hyperoxaluric rats given either
      compound. MATERIALS AND METHODS: Hyperoxaluria (200% above basal) was induced 2
      days prior to commencement of the studies and maintained throughout. After a 3
      days baseline, animals were randomly allocated to a control or treatment group.
      Standard diet containing either (L)-cysteine or OTZ was then fed to the treatment
      groups for 5 days while standard diet alone was fed to the control groups.
      Urinary oxalate excretion was subsequently monitored and average daily rates were
      then compared with basal values. Plasma and urine were analyzed for adduct.
      RESULTS: Both (L)-cysteine and OTZ significantly reduced urinary oxalate
      excretion relative to the basal hyperoxaluric level (28.6 +/- 1.5 micromol./day).
      While (L)-cysteine reduced oxalate excretion over the 5 day treatment period by
      only 7.82 +/- 1.39 micromol./day (27%), OTZ reduced it by 12.34 +/- 1.58
      micromol./day (43%). Adduct could not be detected in plasma or urine in this
      study. CONCLUSIONS: This study confirms that both (L)-cysteine and OTZ are
      effective in reducing urinary oxalate excretion under hyperoxaluric conditions,
      with OTZ being more effective than (L)-cysteine. These compounds were shown to be
      3- to 4-fold more effective in reducing urinary oxalate excretion under
      hyperoxaluric conditions when compared with the results from previous studies
      under normooxaluric conditions.

PMID- 9598566
TI  - Urethral graciloplasty for treatment of female intrinsic sphincter deficiency:
      rationale for the transvaginal approach: an anatomical study.
AB  - PURPOSE: To compare the retropubic and transvaginal approaches in terms of the
      length of gracilis muscle available for female urethral graciloplasty. MATERIALS
      AND METHODS: Two groups of female cadavers were submitted to bilateral gracilis
      muscle dissection, followed by urethral graciloplasty using either the standard
      retropubic approach or the transvaginal approach. The two groups were studied in
      terms of various muscle characteristics, in particular the length of muscle that
      could effectively be wrapped around the bladder neck. RESULTS: Because muscle
      transfer to the perineum was more direct, the transvaginal approach provided a
      greater functional length of gracilis for effective periurethral wrapping than
      the retropubic approach (mean: 8.4 cm. versus 5.2 cm., p = 0.0022). CONCLUSION:
      The transvaginal approach allows a more "proximal" graciloplasty and should
      therefore be evaluated clinically to provide circumferential bladder neck support
      without tension.

PMID- 9598567
TI  - Cytokine repertoire of epithelial cells lining the human urinary tract.
AB  - PURPOSE: To examine the cytokine profile of epithelial cells lining the human
      urinary tract with the aim of differentiating between the constitutive and
      disease-related cytokine production in these tissues. MATERIALS AND METHODS:
      Sections from the renal pelvis, ureter, bladder or urethra were obtained from 22
      patients undergoing urinary tract surgery and were stained with monoclonal
      antibodies to interleukin(IL)-1beta, IL-4, IL-6, IL-8, interferon gamma
      (IFNgamma) and transforming growth factor beta (TGFbeta). Sections were
      classified according to the presence or absence of disease in the tissue.
      RESULTS: Epithelial cells lining the renal pelvis, ureter, bladder or urethra all
      stained for IL-8 and TGFbeta (100%) in disease-free tissues and sections with
      cancer or interstitial cystitis (IC). In contrast, staining for IL-1beta, IL-4,
      IL-6 and IFNgamma varied with the disease state of the patient. Epithelial IL
      1beta staining was absent (0%) in sections from healthy bladder, but positive in
      tissues with IC or cancer-associated pathology (50 to 100%). IL-6 staining was
      detected in the epithelial layer of several patients with IC or cancer related
      pathology, but only in cells with non-epithelial morphology and not in disease
      free tissues. IFNgamma and IL-4 staining were only observed in patients with IC
      and only in cells with non-epithelial morphology. CONCLUSIONS: The results show
      that epithelial cells from all parts of the urinary tract constitutively produce
      IL-8 and TGFbeta and suggest that the production of other cytokines varies with
      the disease of the patient. Constitutive cytokine production provides the basis
      for a rapid host response, in the defense against mucosal attack by microbes or
      toxic agents.

PMID- 9598568
TI  - Detrusor properties in myelomeningocele patients: in vitro study.
AB  - PURPOSE: To characterize detrusor properties of myelomeningocele (MMC) bladders
      which failed conventional therapy. MATERIALS AND METHODS: Bladder strips from
      five end-stage MMC patients were compared with those from five patients with
      vesicoureteric reflux. The active and passive properties of the detrusor muscles
      and the effect of different blocking agents on the transmural nerve stimulation
      were studied. RESULTS: A significant decrease in contractility (p = 0.003) and
      increased rigidity (p = 0.019) was found in MMC group. In the control group,
      atropine blocked 77.7% of the detrusor contractility and tetrodotoxin
      demonstrated an equal blocking effect. In MMC group, atropine blocked 58.2% and
      tetrodotoxin blocked 77.4% of the detrusor contractility. CONCLUSION: MMC
      bladders showed decreased contractility and increased rigidity. In MMC group, the
      atropine-resistant component which is blocked by tetrodotoxin signifies the
      possible existence of non-adrenergic, non-cholinergic neurotransmitters (NANC).
      Further studies are needed to possibly improve the pharmacological therapy of the
      myelomeningocele detrusor.

PMID- 9598569
TI  - Expression of beta3-adrenoceptors in rat detrusor smooth muscle.
AB  - PURPOSE: To investigate the expression of beta-adrenoceptor (AR) subtypes
      responsible for detrusor smooth muscle relaxation. MATERIALS AND METHODS:
      Isolated rat detrusor smooth muscle was examined by tension measurement and
      reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Norepinephrine
      (NE), epinephrine (EP) and isoproterenol (ISO) were found to relax the detrusor
      muscle pre-contracted by 6 x 10(-7) M carbachol in the presence of 10(-6) M
      phentolamine. NE relaxed the detrusor muscle as potently as EP. This potency
      order (NE=EP) thus indicated the beta-ARs of the rat detrusor muscle to possibly
      be a beta1 subtype. However, in the presence of 10(-6) M propranolol, beta1- and
      beta2- but not beta3-AR antagonist, NE showed a more potent relaxation than EP.
      This observation indicated that the rat detrusor muscle also possesses beta3-AR.
      RT-PCR revealed all three subtypes of beta-AR mRNA, namely beta1-, beta2- and
      beta3-AR mRNA, to be expressed in rat detrusor smooth muscle cells. CONCLUSION:
      We concluded that beta3-ARs exist in rat detrusor smooth muscle based on both
      pharmacological and molecular biological studies. Based on these findings, beta
      ARs of rat detrusor smooth muscle are considered to be mixed populations
      consisting of three subtypes which play an important role in relaxing smooth
      muscle in response to catecholamines.

PMID- 9598570
TI  - Synergistic action of steroids and spermatocele fluid on in vitro proliferation
      of prostate stroma.
AB  - PURPOSE: Our goal is to understand human prostate growth phenomena potentially
      important to BPH development and growth. The objective of the present study is to
      characterize in vitro prostate stromal proliferative factors in testis epididymal
      secretions. MATERIALS AND METHODS: Human spermatocele fluids were used as a
      source of testicular epididymal plasma (STEP). Primary cultures of human prostate
      stromal cells were routinely grown in RPMI-1640 with 10% fetal bovine serum.
      During a 6-day experimental period, cells were cultured in RPMI-1640 in the
      absence of serum but supplemented with ITS. Whole STEP, ether stripped STEP, or
      heparin affinity column treated STEP was included in the culture medium with and
      without the addition of testosterone (T), dihydrotestosterone (DHT), or estradiol
      (E). Results of these treatments were assessed by cell counts. Antibodies against
      smooth muscle myosin heavy chain, smooth muscle alpha actin, and prolyl-4
      hydroxylase were utilized in immunocytochemical characterization of cultured
      cells. RESULTS: Whole STEP stimulated prostatic stromal cells derived from
      prostates of 15, 45, 70 and 72-year-old men. Treatment of STEP by ether stripping
      or heparin affinity column exposure did not result in a significant reduction in
      cell counts. With the exception of the 15-year-old specimen, addition of T or DHT
      to ether stripped STEP resulted in a significant increase in cell counts over
      that of ether stripped STEP treatment alone. Preliminary immunocytochemical
      evaluation indicated the presence of variable mixture of fibroblasts,
      myofibroblasts, and smooth muscle cells in these cultures. CONCLUSIONS: These in
      vitro observations indicate that testis epididymal secretions contain
      androgen/STEP synergistic and androgen independent STEP factors promoting
      prostate stromal growth. These factors are not heparin binding. These
      observations are consistent with the concept that, in addition to the production
      of steroids, the testis produces non-androgenic factors that act in concert with,
      as well as independently of, androgen to stimulate prostatic growth.

PMID- 9598571
TI  - The presence of Mullerian inhibiting substance binding sites in human sperm.
AB  - PURPOSE: The binding of Mullerian inhibiting substance (MIS) to human sperm was
      investigated using immunohistological techniques. MATERIALS AND METHODS: Sperm
      from 5 normal donors and 6 subfertile men were studied. Whole or thin-sectioned
      sperm were incubated without or with recombinant human MIS (0.5 microg./ml.). MIS
      binding was identified under light microscopy (LM) using rabbit anti-human MIS
      antibodies tagged with goat IgG-horseradish peroxidase and diaminobenzidine as
      substrate, or by scanning and transmission electron microscopy (SEM and TEM)
      using gold labeled goat IgG. Intracellular MIS binding in sperm sections was
      examined by TEM. Antibodies were omitted in the controls. RESULTS: Under LM, DAB
      staining was present on sperm incubated with or without MIS and absent on
      controls. Using SEM, gold particles were found primarily on the surfaces of the
      sperm head with less binding to the tail. With TEM, the clustering of gold
      particles around the head of sperm represents MIS binding, but very few or no
      gold particles could be found associated with the sperm tail. MIS binding was
      also found associated with intracellular structures, but only within the head of
      the sperm. Overall, less gold particle binding was present in subfertile compared
      with normal sperm. CONCLUSIONS: These results suggest that MIS is bound to the
      sperm surface and sperm from normally fertile men have increased MIS binding. The
      function of MIS in sperm is unknown, but the presence of MIS binding suggests a
      direct role(s) in sperm function.

PMID- 9598572
TI  - Development of fluoroquinolone resistance and mutations involving GyrA and ParC
      proteins among Neisseria gonorrhoeae isolates in Japan.
AB  - PURPOSE: To investigate the development of fluoroquinolone resistance among
      Neisseria gonorrhoeae isolates in Japan and the frequency and patterns of
      mutations involving the GyrA and ParC proteins, which confer quinolone resistance
      to the bacteria, in isolates. MATERIALS AND METHODS: Antimicrobial
      susceptibilities of 145 gonococcal isolates, including 79 isolated from February
      1992 through February 1993 and 66 isolated from February 1995 through February
      1996, to six fluoroquinolones and several other antibiotics were compared with
      those of 27 isolates obtained from 1981 through 1984. To identify mutations in
      gyrA and parC genes of the isolates, the quinolone resistance-determining regions
      of the gyrA and parC genes were PCR-amplified and the PCR products were directly
      sequenced. RESULTS: The minimum inhibitory concentration for 90% of strains
      (MIC90) values of norfloxacin for the isolates from 1992 to 93 (4 microg./ml.)
      and 1995 to 96 (8 microg./ml.) were 16- and 32-fold, respectively, higher than
      those for isolates from 1981 to 84 (0.25 microg./ml.). The MIC90 values of
      ciprofloxacin for isolates from 1992 to 93 (0.5 microg./ml.) and 1995 to 96 (1
      microg./ml.) showed increase of 8- and 16-fold, respectively, in comparison with
      those from 1981 to 84 (0.063 microg./ml.). The isolates from 1992 to 93 and 1995
      to 96 were also less susceptible to newer fluoroquinolones including
      levofloxacin, sparfloxacin, DU-6859a and AM-1155, as compared with those from
      1981 to 84. In 46 (67.6%) and 16 (23.5%) of the 68 gonococcal strains sequenced,
      GyrA and ParC mutations were identified, respectively. No ParC substitutions were
      identified in any isolates without co-existence of the GyrA mutation. A Ser-91 to
      Phe mutation, which was detected in 30 (65.2%) of the 46 isolates with GyrA
      mutations, was the most common GyrA mutation. Mutants with the single Ser-91 to
      Phe substitution in GyrA were 12-fold and at least 13-fold, respectively, less
      susceptible to norfloxacin and ciprofloxacin than the wild type. CONCLUSIONS: The
      results obtained in this study suggest that a high prevalence of gonococcal
      isolates with the Ser-91 to Phe mutation in GyrA has reduced the susceptibility
      of this organism to fluoroquinolones in Japan.

PMID- 9598573
TI  - Quantitative immunohistochemical analysis of insulin-like growth factor binding
      protein-3 in human prostatic adenocarcinoma: a prognostic study.
AB  - PURPOSE: We sought to characterize and quantitate the expression of IGFBP-3 in
      adenocarcinoma of the prostate and to test whether it correlated with tumor
      differentiation determined by Gleason grade. We also investigated the potential
      of using IGFBP-3 as a prognostic indicator of clinically localized prostate
      cancer. MATERIALS AND METHODS: Initially we evaluated the expression of IGFBP-3
      in six normal and twenty neoplastic prostates using standard immunohistochemical
      techniques (study 1). We then obtained radical prostatectomy specimens from
      twenty-four patients with a preoperative diagnosis of clinically localized
      prostate adenocarcinoma and five year follow up information, and nine normal
      prostates from organ donors or from patients undergoing cystoprostatectomy (study
      2). All specimens were immunostained with a polyclonal anti-human IGFBP-3
      antibody. A single pathologist reviewed all sections and assigned a Gleason grade
      to each cancer focus. Using computer-assisted video image analysis, we quantified
      the intensity of IGFBP-3 immunostaining of each cancer focus and of normal
      controls. RESULTS: Normal prostatic epithelium showed intense cytoplasmic IGFBP-3
      staining. The stromal compartment showed less intense staining, although there
      were occasional areas with strong immunoreactivity. The cellular distribution of
      IGFBP-3 staining in prostatic adenocarcinoma was comparable to normal tissue;
      however, the intensity of detectable staining in neoplastic epithelial cells was
      significantly decreased. Two foci of prostatic intraepithelial neoplasia (PIN)
      demonstrated IGFBP-3 immunoreactivity decreased in comparison to normal
      epithelium, but greater than prostatic adenocarcinoma. Histologically normal
      epithelium surrounding cancer foci also showed decreased immunostaining for IGFBP
      3 compared with normal prostate. The marked decrease in immunostaining intensity
      of IGFBP-3 in prostate adenocarcinoma was not associated with Gleason grade or
      with clinical outcome. CONCLUSION: Malignant transformation of prostatic
      epithelium was associated with a significant decrease in the amount of
      immunoreactive IGFBP-3 (p <0.0001); however, this parameter did not correlate
      with Gleason grade of the tumor or with patient outcome. The decrease in
      immunostaining intensity of IGFBP-3 in all Gleason grades and in PIN suggests
      that lower expression of IGFBP-3 is an early event in prostatic carcinogenesis.
      The finding that decreased IGFBP-3 immunostaining did not correlate with clinical
      outcome suggests that this parameter is not a therapy-guiding prognostic
      indicator for clinically localized prostate cancer.

PMID- 9598574
TI  - Quantitative analysis of smooth muscle fibers in corpus cavernosum of human
      fetuses.
AB  - PURPOSE: Quantify objectively the normative distribution and the percentage of
      smooth muscle fibers in the corpus cavernosum of human fetuses with 24 weeks post
      conception (WPC) of gestational age. MATERIAL AND METHODS: We studied 7 penises
      taken from 7 fresh human fetuses. We analyzed 5 randomized sections from each
      penis and in every section we analyzed 3 fields, totaling 15 fields per penis and
      105 fields for the final results. Immunohistological staining for the smooth
      muscle fibers was used to accentuate the differences between the intracavernous
      structures (smooth muscle fibers and collagen fibers). The fields studied were
      digitized with a final magnification of 450X and a computerized analysis of the
      smooth muscle fibers was performed with image analyzer software. The percentage
      of smooth muscle fibers per standard square area was estimated and the mean value
      was used for each penis. RESULTS: The distribution of smooth muscle fibers in the
      corpus cavernosum of human fetuses with 24 WPC of gestational age ranged from
      17.52% to 27.76% of the total area. The mean value was 22.72% and the standard
      deviation was 3.56. CONCLUSIONS: Our results show that the percentage of smooth
      muscle cells in corpus cavernosum of human fetuses with 24 WPC of gestational age
      is significantly smaller when compared with the data available for adult
      cadavers.

PMID- 9598575
TI  - Cavernosal expandability is an erectile tissue mechanical property which predicts
      trabecular histology in an animal model of vasculogenic erectile dysfunction.
AB  - PURPOSE: Reliable, clinically available, non-invasive measurements able to
      predict trabecular histology without the need for erectile tissue biopsy would
      improve impotence management, since the percentage of trabecular smooth muscle
      content has been shown to be associated with corporal veno-occlusive dysfunction.
      The purpose was to identify whether the erectile tissue mechanical property,
      cavernosal expandability, correlated with the percentage of trabecular smooth
      muscle content in an animal model of hypercholesterolemia and ischemic-induced
      corporal fibrosis. MATERIALS AND METHODS: New Zealand White rabbits (6 to 7
      months old, 3 to 3.5 kg.), were divided into control (n = 7),
      hypercholesterolemic (n = 5, 0.5% cholesterol diet) and atherosclerotic groups (n
      = 8, 0.5% cholesterol diet with balloon de-endothelialization). At 16 weeks, the
      corpora cavernosa were removed en bloc and submerged in physiologic salt
      solution, and volume-pressure data were plotted at 20 mm. Hg pressure intervals
      under trabecular smooth muscle relaxation. Cavernosal expandability, X, (the
      measure of the ability to achieve high corporal expansion at relatively low
      intracavernosal pressure) and tunical distensibility, V(E)/V(F), (relative volume
      of fully erect to flaccid penis) were calculated. Erectile tissue was assessed by
      computer-assisted color histomorphometry with Masson's trichrome stained sections
      (30 to 45 high power fields/animal) to assess percentage of trabecular smooth
      muscle content. RESULTS: The overall mean percentage of trabecular smooth muscle
      content and mean cavernosal expandability values were 45.4 +/- 1.6, 39.2 +/- 0.9,
      33.9 +/- 0.6 and 0.0165 +/- 3.04 x 10(-3), 0.0116 +/- 1.63 x 10(-3), 0.0118 +/-
      1.26 x 10(-3) mm. Hg(-1) for the control, hypercholesterolemic and
      atherosclerotic groups, respectively (r = 0.87). Significant differences in
      trabecular smooth muscle content were observed among all 3 groups, and in
      cavernosal expandability, between control and atherosclerotic groups, as well as
      between control and hypercholesterolemic groups but not between atherosclerotic
      and hypercholesterolemic groups. CONCLUSIONS: The erectile tissue mechanical
      property, cavernosal expandability, correlated with erectile tissue structural
      quality. Since cavernosal histology has been shown to predict corporal veno
      occlusive function, it is hypothesized that the measurement of cavernosal
      expandability may become a valuable functional clinical parameter in the
      diagnosis and treatment of men with erectile dysfunction.

PMID- 9598576
TI  - Complications during renal artery stent placement for atherosclerotic ostial
      stenosis.

PMID- 9598577
TI  - Studies of the KATP channel opening activity of the new dihydropyridine compound
      9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H, 5H)-acridinedione in bladder
      detrusor in vitro.

PMID- 9598578
TI  - The ice-water test in the diagnosis and treatment of the neurogenic bladder.

PMID- 9598579
TI  - In situ hybridization with riboprobes: an overview for veterinary pathologists.
AB  - In situ hybridization using nonradioactively-labeled RNA probes is a technique
      that combines understanding of basic molecular biology and histopathologic
      interpretation. Recombinant or PCR technology can be used to produce probes that
      hybridize with a wide variety of cellular genes and infectious agents.
      Hybridization conditions can be optimized for each probe/target combination.

PMID- 9598580
TI  - A canine model of familial mammary gland neoplasia.
AB  - Intact female Beagles from life-span studies in the Lovelace Respiratory Research
      Institute colony were examined for mammary tumor incidence. The breeding colony,
      founded in 1963, produced five generations from 28 founder females. After
      proportional hazards analysis, two maternal families were shown to have markedly
      different phenotypes, one susceptible and one resistant to mammary neoplasia, as
      compared with the entire colony. When tumors were subdivided into benign and
      malignant based on local invasiveness, familial differences in tumor incidence
      were preserved for each tumor type. Fifty-seven females in the susceptible family
      developed 149 benign and 39 malignant tumors, and 95 females in the resistant
      family developed 70 benign and 20 malignant tumors. The ratio of benign to
      malignant tumors of about 4:1 for both families was higher than expected. Using
      Kaplan-Meier and log-rank analyses, the susceptible family had a 50% malignant
      tumor incidence by age 13.6 years, whereas the resistant family did not have a
      50% incidence until 17.0 years (P = 0.0065). Because of marked censoring, Kaplan
      Meier analyses could not provide an estimate of the 50% benign tumor incidence;
      mean incidence age was calculated instead. These estimates for benign tumors for
      susceptible and resistant families were 10.8 and 13.8 years (P = 0.0001),
      respectively. Using chi(2) tests, families had no differences in the occurrence
      of the types of benign (P = 0.098) or malignant (P = 0.194) tumors or in the
      ratio of benign to malignant tumors (P = 0.778). Immunohistochemical analysis of
      malignant tumors from both families did not demonstrate differences in p53
      mutation rate or p185erbB-2 expression. These results suggest that 1) genetic
      factors produce familial differences in the age of onset of both benign and
      malignant mammary tumors; histologic types do not segregate by family; 2) the
      ratio of benign to malignant tumors is greater than formerly reported; and 3)
      neither p53 nor p185erbB-2 alterations are the basis for the familial
      predisposition.

PMID- 9598581
TI  - Pathogenicity of Mycoplasma synoviae in broiler chickens.
AB  - Six isolates of Mycoplasma synoviae, identified as WVU 1853, K1968, K1858,
      92D8034, F10-2AS, and FMT, were compared for pathogenicity in broiler chickens.
      Specific-pathogen-free chickens were inoculated, in two groups of 20, with each
      isolate by footpad or eyedrop inoculation at 1 day of age and were examined at
      necropsy 7, 14, 28, and 42 days postinoculation. Specimens were taken for
      histopathology, culture, polymerase chain reaction assay, and hemagglutination
      inhibition serology. Isolates were grouped according to pathogenicity on the
      basis of differences in lesion development and tissue distribution in the
      respiratory system, other viscera, and the skeletal system. K1968 (pathogenic)
      induced lesions in all sites examined in both the footpad and eyedrop inoculation
      groups. It was detected in all sites following footpad inoculation and in all
      sites except viscera following eyedrop inoculation. WVU 1853, K1858, and 92D8034
      (moderately pathogenic) induced lesions and were detected in all sites following
      footpad inoculation. With eyedrop inoculation, lesions were identified only in
      upper and lower respiratory sites, and organisms were detected only in upper
      respiratory sites. F10-2AS (moderately pathogenic) was similar; however, footpad
      inoculation failed to induce visceral lesions or permit organism detection in any
      site. F10-2AS was detected in upper and lower respiratory tissues following
      eyedrop inoculation. FMT (mildly pathogenic) induced only upper respiratory
      lesions when either footpad or eyedrop inoculation was used, and detection was
      restricted to upper respiratory sites following eyedrop inoculation. These
      results are useful in comparative evaluations of the virulence of other M.
      synoviae isolates and form a basis for characterization of virulence factors of
      M. synoviae.

PMID- 9598582
TI  - Biphasic thymus response by kittens inoculated with feline immunodeficiency virus
      during fetal development.
AB  - The objective of this study was to assess the response of the feline thymus to
      fetal infection with feline immunodeficiency virus (FIV), an animal model for
      human immunodeficiency virus infection. Thirteen feline embryos from four litters
      were directly inoculated with FIV during the sixth week postbreeding, a period
      corresponding to the late second trimester of pregnancy. Thymus tissue was
      collected and analyzed from randomly selected kittens at 2, 4, and 16 weeks
      postinoculation (PI) and compared to age-matched control kittens that did not
      receive fetal inoculations. Of three kittens evaluated at 2 weeks PI (week 8 of
      gestation), neither thymus:body weight ratio nor histologic structure differed
      from five age-matched control animals. However, analysis of thymocyte
      subpopulations by flow cytometry revealed a significant (P = 0.011) reduction in
      the percentage of cluster of differentiation (CD)4+/CD8+ cells from an average of
      66% in control fetuses to 45% in infected fetuses. FIV RNA transcription,
      assessed by in situ hybridization using an FIVgag RNA probe, was widely
      distributed throughout the thymus in patterns suggestive of both stromal and
      parenchymal infection. By 4 weeks PI (week 1 postpartum), the thymus:body weight
      ratio was significantly reduced (P = 0.007) from 0.36% in five control kittens to
      0.13% in four fetal inoculates. Severely atrophied thymus lobules supported
      minimal virus transcription and mean CD4+/CD8+ thymocyte percentages were lower
      (P = 0.021) in infected kittens (15%) compared to age-matched controls (66%). By
      16 weeks PI (week 12 postpartum), thymus:body weight ratios of six inoculated
      kittens were not significantly different from six age-matched controls,
      suggesting that partial postnatal thymus regeneration had occurred. However,
      despite similar size, the regenerative thymus contained reduced percentages of
      CD4+/CD8+ thymocytes (infected: 40% versus control: 76%; P = 0.009) and increased
      percentages of CD4+/CD8- (11% versus 5%; P = 0.002) and CD4-/CD8+ (16% versus 9%;
      P = 0.035) lymphocytes. These changes were associated with widespread FIV
      transcription within thymic lymphocytes. Thus, the thymus of kittens infected
      with FIV during late fetal development is characterized by two distinct changes:
      neonatal atrophy and postnatal regeneration. Despite a recovery in thymus weight,
      thymus regeneration ineffectively restores the normal phenotypic distribution of
      thymocytes and supports FIV transcription.

PMID- 9598583
TI  - Inflammatory large bowel disease in immunodeficient rats naturally and
      experimentally infected with Helicobacter bilis.
AB  - Proliferative and ulcerative typhlitis, colitis, and proctitis were found
      incidentally in a breeding colony of male athymic nude (Cr:NIH-rnu) rats. Within
      the crypts of the large intestine, modified Steiner's silver stain revealed
      spiral organisms that were identified by culture, polymerase chain reaction, and
      sequencing to be Helicobacter bilis. The large bowel disease was reproduced in H.
      bilis-free male athymic nude rats that were injected intraperitoneally with a
      culture of H. bilis from the affected colony. The organism was isolated from the
      feces and cecum of the experimentally infected rats. H. bilis should be
      considered a potential pathogen in immunocompromised rats. The infection in
      immunocompromised rats may serve as an animal model for inflammatory large bowel
      disease.

PMID- 9598584
TI  - Nested polymerase chain reaction and in situ hybridization for diagnosis of
      canine herpesvirus infection in puppies.
AB  - The usefulness of two nucleic acid detection systems in suspected cases of
      spontaneous canine herpesvirus (CHV) infection in puppies was evaluated. Formalin
      fixed, paraffin-embedded tissues from seven 1-3-week-old naturally infected
      puppies with lesions characteristic of CHV infection were investigated in a
      retrospective study. Nested polymerase chain reaction (PCR) and nonradioactive in
      situ hybridization (ISH) were used to detect nucleotide sequences of the CHV
      thymidine kinase (TK) gene. According to the original necropsy reports, CHV was
      isolated in four of the seven puppies using primary canine lung and/or kidney
      cells. In all seven puppies, gross and histologic lesions consisted of
      disseminated focal necroses and hemorrhages predominantly in kidneys, lung,
      liver, and spleen. In addition, few small amphophilic intranuclear inclusion
      bodies were detected by light microscopy mainly in epithelial cells of kidney,
      lung, and liver. ISH was performed with a 111-base-pair (bp) digoxigenin-labeled
      double-stranded DNA probe. Viral DNA was detected in the nuclei of cells near and
      within lesions. Various cell types, including bronchiolar and alveolar epithelial
      cells, hepatocytes, renal tubular epithelial cells, neurons, fibrocytes, cardiac
      myocytes, and endothelial cells, were positive for viral DNA. PCR amplification
      products of the expected length of 168 bp containing the expected cleavage site
      for the restriction enzyme EcoRI, derived from paraffin blocks containing lung,
      kidney, and liver tissues, were detected in all seven puppies. The specificity of
      the obtained amplicon was further confirmed by Southern blot analysis. ISH and
      PCR are both useful methods for diagnosing CHV infection in formalin-fixed,
      paraffin-embedded tissues and are highly specific and sensitive methods for
      further investigations of the pathogenesis of CHV-induced lesions.

PMID- 9598585
TI  - Lafora bodies associated with neurologic signs in a cat.
AB  - Lafora bodies (polyglucosan deposits) were identified in the brain of a young
      adult cat with neurologic signs characterized by intermittent but progressively
      worsening head and body tremors. The cerebellar cortex was the most severely
      affected area of brain, and the deposits were identified within Purkinje cell
      bodies and processes and throughout the neuropil. The association of Lafora
      bodies with neurologic signs, occurrence of deposits within neuronal perikarya,
      and distribution primarily within the cerebellar cortex are features distinct
      from the more commonly recognized situation in which Lafora bodies occur as
      incidental lesions in cats.

PMID- 9598586
TI  - Testicular yolk sac carcinoma in a calf.
AB  - A testicular yolk sac carcinoma (YSCA) was diagnosed in a 28-day-old male
      Japanese black calf. Macroscopically, the abdominal cavity was filled with
      reddish gelatinous masses of various sizes. There were no testes in the scrotum
      or pelvic cavity. Histologically, the masses consisted of the tissues showing a
      variety of patterns; loose reticular network, pseudopapillary arrangement,
      festoon, solid nest, and labyrinthine pattern. Tumor cells were round to oval,
      with single central or polar nuclei with sharply defined nuclear borders and
      deeply basophilic chromatin. Tumor cells sometimes had glycogen granules,
      periodic acid-Schiff (PAS)-positive inclusions, or sudanophilic droplets in their
      cytoplasm. Hyaline matrices were found in extracellular areas and were intensely
      PAS positive. Immunohistochemically, most of the tumor cells and hyaline matrices
      had positive reactivity to anti-alpha-fetoprotein and anti-placental-alkaline
      phosphatase antibodies. Positive reaction to anti-laminin antibody appeared only
      in hyaline matrices. This is the first case of a tumor in a domestic animal with
      histologic and immunohistochemical features analogous to those of human YSCA,
      endodermal sinus type.

PMID- 9598587
TI  - Canine peripheral nerve sheath tumor with eosinophilic cytoplasmic globules.
AB  - A 13-year-old male Shetland Sheepdog had a subcutaneous tumor in the left
      brachium. The tumor was removed and recurred several times at 5, 13, 16, 22, and
      31 months after the initial presentation. Histologically, the removed nodules
      from the fourth resection were composed of neoplastic proliferation of round to
      fusiform cells, which possessed eosinophilic globules in their cytoplasm. The
      globules were periodic acid-Schiff positive and diastase resistant. Positive
      reactions for acid phosphatase were observed in the cytoplasm of the tumor cells.
      Ultrastructurally, these globules consisted of membrane-bound, dense structures
      containing dense granules, lucent vacuoles, and homogeneous materials. The
      recurrent tumors removed at the fifth resection consisted of spindle cell
      proliferation arranged in interlacing fascicles with wavy nuclei and containing a
      small number of cells with cytoplasmic globules. The tumor cells were
      immunoreactive to vimentin, S-100 protein, myelin basic protein, and neuron
      specific enolase. The tumor was diagnosed as a peripheral nerve sheath tumor with
      eosinophilic cytoplasmic globules. These findings are unique for the histogenesis
      of granular cell tumors.

PMID- 9598588
TI  - Immunohistochemical localization of apolipoprotein B-100 (ApoB-100) and
      expression of glutathione peroxidase (GSH-PO) in canine atherosclerotic lesions.
AB  - We used immunohistochemistry to localize canine Apolipoprotein B-100 (CApoB-100)
      and glutathione peroxidase (GSH-PO) in canine atherosclerotic lesions. CApoB-100
      was deposited in the tunica intima and cytoplasms of infiltrating macrophages in
      early atherosclerotic lesions. In advanced atherosclerotic lesions, the cystic
      space of the lesions contained a large amount of CApoB-100 immunoreactive
      material. Expression of GSH-PO was recognized in the foamy cytoplasm of
      macrophages and smooth muscle cells in the early and advanced atherosclerotic
      lesions. These results indicate that expression of GSH-PO is closely associated
      with the deposition of CApoB-100. In addition, they suggest that, as in human
      atheromas, low-density lipoprotein (LDL) is peroxidized and changed into modified
      LDL. Deposition of modified LDL (oxidized or acetylated) may be a critical step
      in the formation of canine atherosclerotic lesions.

PMID- 9598589
TI  - Clinical and morphologic features of mucopolysaccharidosis type II in a dog:
      naturally occurring model of Hunter syndrome.
AB  - A 5-year-old male Labrador Retriever had progressive incoordination, visual
      impairment, and exercise intolerance. Coarse facial features, macrodactylia,
      unilateral corneal dystrophy, generalized osteopenia, progressive neurologic
      deterioration, and a positive urine spot test for acid mucopolysaccharides
      suggested mucopolysaccharidosis. Intracytoplasmic vacuoles were most prevalent in
      epithelial cells, endothelial cells, and histiocytes of liver, kidney, thyroid
      gland, and spleen. Ultrastructural examination disclosed electron-lucent
      floccular to lamellar membrane-bound storage material characteristic of
      mucopolysaccharides. Periodic acid-Schiff-positive intracytoplasmic material was
      identified in multiple neurons in the medulla, pontine nucleus, cerebellum, and
      spinal gray matter horns. Biochemical assays identified a deficiency in iduronate
      2-sulfatase (IDS) activity in cultured dermal fibroblasts compared with normal
      dogs. Hair root analysis for IDS showed that the dam was a carrier of X-linked
      Hunter syndrome and that a phenotypically normal male littermate of the affected
      dog was normal. This is the first report of Hunter syndrome or
      mucopolysaccharidosis type II in a dog.

PMID- 9598590
TI  - A 17mer peptide interferes with acidification-induced uncoupling of connexin43.
AB  - Structure/function analysis shows that the carboxyl terminal (CT) domain of
      connexin43 (Cx43) is essential for the chemical regulation of cell-cell
      communication. Of particular interest is the region between amino acids 260 and
      300. Structural preservation of this region is essential for acidification
      induced uncoupling (ie, pH gating). In this study, we report data showing that a
      17mer peptide of the same sequence as amino acids 271 to 287 of Cx43
      (CSSPTAPLSPMSPPGYK) can prevent pH gating of Cx43-expressing oocytes. Experiments
      were carried out in pairs of Xenopus oocytes previously injected with connexin38
      antisense and expressing wild-type Cx43. Junctional conductance was measured
      electrophysiologically. pHi was determined from the light emission of the proton
      sensitive dye dextran-seminaphthorhodafluor. Intracellular acidification was
      induced by superfusion with a bicarbonate-buffered solution gassed with a
      progressively increasing concentration of CO2. Injection of water alone into both
      oocytes of a Cx43-expressing pair or injection of a peptide from region 321 to
      337 of Cx43 did not modify pH sensitivity. However, injection of a polypeptide
      corresponding to amino acids 241 to 382 of Cx43 interfered with the ability of
      gap junctions to close on acidification. Similar results were obtained when a
      17mer peptide (region 271 to 287) was injected into both oocytes of the pair.
      Normal Cx43 pH gating was observed if (1) the amino acid sequence of the 17mer
      peptide was scrambled or (2) the N and the C ends of the 17mer peptide were not
      included in the sequence. This is the first demonstration of a molecule that can
      interfere with the chemical regulation of connexin channels in a cell pair. The
      data may lead to the development of small molecules that can be used in Cx43
      expressing multicellular preparations to study the role of gap junction
      regulation in normal as well as diseased states.

PMID- 9598591
TI  - Cardiac and extracardiac expression of Csx/Nkx2.5 homeodomain protein.
AB  - Csx/Nkx2.5 is an evolutionary conserved homeobox gene related to the Drosophila
      tinman gene, which is essential for the dorsal mesoderm formation. Expression of
      Csx/Nkx2.5 mRNA is the earliest marker for heart precursor cells in all
      vertebrates so far examined. Previous studies have demonstrated that Csx/Nkx2.5
      mRNA is highly expressed in the heart and at lower levels in the spleen, tongue,
      stomach, and thyroid in the murine embryo. Since some developmental genes are
      regulated by posttranscriptional mechanisms, we analyzed the developmental
      pattern of Csx protein expression at the single-cell level using Csx-specific
      antibodies. Immunohistochemical analysis of murine embryos at 7.8 days post
      coitum revealed that Csx protein is strongly expressed in the nucleus of
      endodermal and mesodermal cells in the cardiogenic plate. Subsequently, in the
      heart, Csx protein was detected only in the nucleus of myocytes of the atrium and
      the ventricle through the adult stage. During the fetal period, Csx protein
      expression in the nucleus was also noted in the spleen, stomach, liver, tongue,
      and anterior larynx. Unexpectedly, confocal microscopy revealed that Csx
      immunoreactivity was detected only in the cytoplasm of a subset of cranial
      skeletal muscles. Csx protein was not detected in the thyroid glands. The
      expression of Csx protein in all organs was markedly downregulated after birth
      except in the heart. These results raise the possibility that Csx/Nkx2.5 may play
      a role in the early developmental process of multiple tissues in addition to its
      role in early heart development.

PMID- 9598592
TI  - Dynamic Ca2+-induced inward rectification of K+ current during the ventricular
      action potential.
AB  - Inward rectification, an important determinant of cell excitability, can result
      from channel blockade by intracellular cations, including Ca2+. However, mostly
      on the basis of indirect arguments, Ca2+-mediated rectification of inward
      rectifier K+ current (IK1) is claimed to play no role in the mammalian heart. The
      present study investigates Ca2+-mediated IK1 rectification during the mammalian
      ventricular action potential. Guinea pig ventricular myocytes were patch-clamped
      in the whole-cell configuration. The action potential waveform was recorded and
      then applied to reproduce normal excitation under voltage-clamp conditions.
      Subtraction currents obtained during blockade of K+ currents by either 1 mmol/L
      Ba2+ (IBa) or K+-free solution (I0K) were used to estimate IK1. Similar time
      courses were observed for IBa and I0K; both currents were strongly reduced during
      depolarization (inward rectification). Blockade of L-type Ca2+ current by
      dihydropyridines (DHPs) increased systolic IBa and I0K by 50.7% and 254.5%,
      respectively. beta-Adrenergic stimulation, when tested on I0K, had an opposite
      effect; ie, it reduced this current by 66.5%. Ryanodine, an inhibitor of
      sarcoplasmic Ca2+ release, increased systolic IBa by 47.7%, with effects similar
      to those of DHPs. Intracellular Ca2+ buffering (BAPTA-AM) increased systolic IBa
      by 87.7% and blunted the effect of DHPs. Thus, IK1 may be significantly reduced
      by physiological Ca2+ transients determined by both Ca2+ influx and release.
      Although Ca2+-induced effects may represent only a small fraction of total IK1
      rectification, they are large enough to affect excitability and repolarization.
      They may also contribute to facilitation of early afterdepolarizations by
      conditions increasing Ca2+ influx.

PMID- 9598593
TI  - Source of electrocardiographic ST changes in subendocardial ischemia.
AB  - To clarify the source of electrocardiographic ST depression associated with
      ischemia, a sheep model of subendocardial ischemia was developed in which
      simultaneous epicardial and endocardial ST potentials were mapped, and a computer
      model using the bidomain technique was developed to explain the results. To
      produce ischemia in different territories of the myocardium in the same animal,
      the left anterior descending coronary artery and left circumflex coronary artery
      were partially constricted in sequence. Results from 36 sheep and the computer
      simulation are reported. The distributions of epicardial potentials from either
      ischemic source were very similar (r=0.77+/-0.14, P<0.0001), with both showing ST
      depression on the free wall of the left ventricle and no association between the
      ST depression and the ischemic region. However, endocardial potentials showed
      that ST elevation was directly associated with the region of reduced blood flow.
      Insulating the heart from the surrounding tissue with plastic increased the
      magnitude of epicardial ST potentials, which was consistent with an
      intramyocardial source. Increasing the percent stenosis of a coronary artery
      increased epicardial ST depression at the lateral boundary and resulted in ST
      elevation starting from the ischemic center as ischemia became transmural.
      Computer simulation using the bidomain model reproduced the epicardial ST
      patterns and suggested that the ST depression was generated at the lateral
      boundary between ischemic and normal territories. ST depression on the epicardium
      reflected the position of this lateral boundary. The boundaries of ischemic
      territories are shared, and only those appearing on the free wall contribute to
      external ST potential fields. These effects explain why body surface ST
      depression does not localize cardiac ischemia in humans.

PMID- 9598594
TI  - ATP-dependent activation of the atrial acetylcholine-induced K+ channel does not
      require nucleoside diphosphate kinase activity.
AB  - Prior reports by others have shown that cytoplasmically applied ATP can activate
      the acetylcholine-induced K+ channel in inside-out atrial membrane patches when
      no guanine nucleotides are present in the solution bathing the cytosolic face of
      the membrane. A nucleoside diphosphate kinase mechanism was proposed to explain
      the activation by ATP. We show in the present study that cytoplasmic
      adenylylimidodiphosphate mimics the activation by ATP. Unlike ATP, the activation
      by adenylylimidodiphosphate does not subside on washout. Although commercially
      available adenylylimidodiphosphate is contaminated by guanylylimidodiphosphate,
      the activation by adenylylimidodiphosphate still occurs after HPLC purification
      to remove guanine nucleotide contamination. Adenylylimidodiphosphate does not
      support phosphotransferase activity by nucleoside diphosphate kinase. Therefore,
      nucleoside diphosphate kinase activity cannot explain the activation of atrial
      acetylcholine-induced K+ current by ATP and adenylylimidodiphosphate. We
      hypothesize that the activation by millimolar concentrations of ATP is due to
      binding of adenine nucleotide to the guanine nucleotide binding site of the G
      protein(s) responsible for stimulating the acetylcholine-induced K+ current.

PMID- 9598596
TI  - Expression of extracellular matrix proteins accompanies lesion growth in a model
      of intimal reinjury.
AB  - Reinjury of rat arterial lesions induces an increase in lesion size that is not
      associated with an increase in cell number. In this study, matrix volume was
      examined after reinjury to preexisting lesions, and the kinetics of matrix gene
      expression and activity of proteolytic enzymes in the lesion were evaluated.
      Volume densitometry in intima showed a significant increase in matrix volume 28
      days after the reinjury, although no change was observed at 14 days. Three common
      vascular matrix molecules, alpha1(I)procollagen, tropoelastin, and fibronectin,
      were expressed highly at 7 days after the reinjury. Expression of tropoelastin
      remained upregulated for the entire 28 days after the reinjury, whereas
      alpha1(I)procollagen and fibronectin returned to the control level by 28 days.
      Protease activity was also increased after reinjury. Within days, a marked
      increase in urokinase plasminogen activator activity was observed in intima, and
      this activity decreased to control level by 14 days. The activity of tissue
      plasminogen activator did not change. The 95-kDa gelatinolytic activity was
      increased 1 to 2 days after the reinjury, but no change in other gelatinolytic
      activities was observed. These findings demonstrate that the accumulation of
      extracellular matrix is important in the increase in lesion size after reinjury
      and that a balance of matrix synthesis and degradation may explain why no change
      in matrix volume was detected until 28 days after the reinjury.

PMID- 9598595
TI  - Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation
      without causing inhibition of platelet aggregation or altering hemostatic
      parameters after angioplasty in rat.
AB  - An antibody was raised in rabbits against SFFLRNPSEDTFEQF peptide, which is an
      NH2-terminal peptide of the thrombin-cleaved rat thrombin receptor. In vitro, the
      antibody inhibited rat smooth muscle cell proliferation but had no effect on rat
      platelet aggregation or clotting time. These data indicate that the antibody is a
      specific blocker of the thrombin receptor-signaling pathway in rat smooth muscle
      cells but does not work as a blocker in rat platelets, suggesting the existence
      of a second thrombin receptor in the platelets. Using an in vivo balloon catheter
      induced injury model in rats, we examined the effect of the anti-rat thrombin
      receptor IgG on intimal smooth muscle cell accumulation 2 weeks after
      angioplasty. Analysis of the ratio of intimal to medial cross-sectional areas
      showed that injection of immune IgG resulted in 43.7% and 53.1% reduction
      (P<0.01) of neointimal smooth muscle cell accumulation compared with saline and
      nonimmune IgG treatment, respectively. Moreover, the injection of immune IgG
      caused a significant decrease of thrombin receptor mRNA expression and also 40.5%
      and 43.0% decreases (P<0.01) of the proliferating cell nuclear antigen (PCNA)
      index in the intima compared with the PCNA index after saline and nonimmune IgG
      treatment, respectively. The suppression of the PCNA index was also observed in
      the immune IgG-treated group at an early stage after angioplasty. These results
      suggest that thrombin receptor activation is involved in the proliferation and
      accumulation of neointimal smooth muscle cells induced by balloon injury.

PMID- 9598597
TI  - Sequential injury of the rabbit abdominal aorta induces intramural coagulation
      and luminal narrowing independent of intimal mass: extrinsic pathway inhibition
      eliminates luminal narrowing.
AB  - We hypothesized that activation of the coagulation cascade is involved in
      arterial remodeling in response to sequential injury. An active site-inhibited
      recombinant human factor VIIa (FVIIai) was used to inhibit tissue factor, the
      primary cofactor in the extrinsic pathway of coagulation, in a sequential balloon
      injury model of the rabbit abdominal aorta. Single balloon injury produced
      limited intimal thickening at 3 weeks (intimal area, 0.40+/-0.05 mm2) and no loss
      in luminal area (12.2+/-0.9 mm2 before injury and 12.1+/-0.9 mm2 at 6 weeks after
      injury). Sequential balloon injury, 3 weeks after the first balloon denudation,
      produced a progressive loss of lumen, with 22% and 47% loss of luminal area,
      respectively, at 3 and 6 weeks. Luminal loss could not be accounted for by
      intimal growth (at 3 weeks after sequential injury, the intimal area was 0.47+/
      0.08 mm2, <4% of the initial luminal area). Sequential injury acutely produced
      extensive mural and intramural fibrin deposition. Treatment with FVIIai inhibited
      both the fibrin deposition and the chronic loss of lumen. At 3 weeks after
      sequential injury, luminal cross-sectional areas were 9.8+/-0.6 mm2 for control
      rabbits and 14.3+/-1.4 mm2 for FVIIai-treated rabbits. Neither neointimal area
      nor cell proliferation was reduced by FVIIai treatment. The intimal cell
      proliferation index 3 days after injury was 7.6+/-1.1% in control rabbits versus
      5.8+/-1.1% in treated rabbits (P>0.05). These results indicate that tissue factor
      is an important mediator of coagulation in repeat injury and implicate the
      extrinsic coagulation cascade in a blood vessel remodeling response that is
      independent of neointimal growth but leads to extensive loss of lumen.

PMID- 9598598
TI  - Role of nitric oxide in the angiogenic response in vitro to basic fibroblast
      growth factor.
AB  - Angiogenesis is a complex process that involves the activation of quiescent
      endothelial cells (ECs) to a proliferative and migratory phenotype and,
      subsequently, their redifferentiation to form vascular tubes. We hypothesized
      that NO contributes to angiogenesis by terminating the proliferative action of
      angiogenic growth factors and initiating a genetic program of EC differentiation.
      Human umbilical vein ECs (HUVECs) and calf pulmonary artery ECs (CPAECs) were
      grown directly on plastic dishes or on three-dimensional fibrin matrices. In the
      absence of fibrin, treatment with NO-donor compounds, such as S-nitroso-N
      acetylpenicillamine (SNAP, 0.1 and 0.4 mmol/L), produced a dose-dependent
      inhibition of proliferation in both cell lines, whereas the inhibition of
      endogenous NO production using NG-nitro-L-arginine methyl ester (L-NAME, 1
      mmol/L) or NG-monomethyl-L-arginine (L-NMMA, 1 mmol/L) significantly increased
      proliferation of the CPAECs. The addition of basic fibroblast growth factor
      (bFGF, 30 ng/mL) increased the expression of endothelial NO synthase mRNA and the
      production of NO in both cell types when cultured on three-dimensional fibrin
      gels and produced profound morphological changes characterized by the appearance
      of extensive capillary-like vascular structures and the loss of EC monolayers.
      These changes were quantified by measuring total tube length per low-power field
      (x100), and a differentiation index was derived using the ratio of tube length
      over area covered by residual EC monolayer. In the absence of additional
      angiogenic factors, the differentiation index was low for both HUVECs and CPAECs
      (control, 1.16+/-0.19 and 2.07+/-0.87, respectively). Treatment with bFGF
      increased the differentiation index significantly in both cell types (10.59+/
      2.03 and 20.02+/-5.01 for HUVECs and CPAECs, respectively; P<.05 versus control),
      and the addition of SNAP (0.4 mmol/L) mimicked the angiogenic response to bFGF
      (8.57+/-1.34 and 12.20+/-3.49 for HUVECs and CPAECs, respectively; P<.05 versus
      control). Moreover, L-NAME inhibited EC tube formation in response to bFGF in a
      dose-response manner, consistent with a role of endogenous NO production in EC
      differentiation in this angiogenic model. These findings suggest that NO may act
      as a crucial signal in the angiogenic response to bFGF, terminating the
      proliferative actions of angiogenic growth factors and promoting EC
      differentiation into vascular tubes.

PMID- 9598600
TI  - Novel antioxidant action of aspirin may contribute to its beneficial
      cardiovascular actions.

PMID- 9598599
TI  - Aspirin increases ferritin synthesis in endothelial cells: a novel antioxidant
      pathway.
AB  - Aspirin has recently been shown to increase endothelial resistance to oxidative
      damage. However, the mechanism underlying aspirin-induced cytoprotection is still
      unknown. Using cultured cells, the present study investigates the effect of
      aspirin on the expression of ferritin, a cytoprotective protein that sequesters
      free cytosolic iron, the main catalyst of oxygen radical formation. In bovine
      pulmonary artery endothelial cells, aspirin at low antithrombotic concentrations
      (0.03 to 0.3 mmol/L) induced the synthesis of ferritin protein in a time- and
      concentration-dependent fashion up to 5-fold over basal levels, whereas ferritin
      H (heavy chain) mRNA remained unaltered. Aspirin-induced cytoprotection from
      hydrogen peroxide toxicity was mimicked by exogenous iron-free apoferritin but
      not iron-loaded ferritin, demonstrating the antioxidant function of newly
      synthesized ferritin under these conditions. Ferritin induction by aspirin was
      specific in that other nonsteroidal anti-inflammatory drugs such as salicylic
      acid, indomethacin, or diclofenac failed to alter ferritin protein levels.
      Aspirin-induced ferritin synthesis was abrogated in the presence of the iron
      chelator desferrioxamine, pointing to an interaction of aspirin with iron
      responsive activation of ferritin translation. Together, our results suggest
      induction of ferritin as a novel mechanism by which aspirin may prevent
      endothelial injury in cardiovascular disease, eg, during atherogenesis.

PMID- 9598601
TI  - A case for the future.

PMID- 9598602
TI  - Fantastic issue!

PMID- 9598603
TI  - On the use and misuse of statistical methods.

PMID- 9598604
TI  - A statistical artifact.

PMID- 9598605
TI  - Nonextraction treatment of unilateral Class II, Division 1 malocclusion with
      asymmetric headgear.

PMID- 9598606
TI  - Rapid palatal expansion. Part 2: Dentoskeletal changes in cats with patent versus
      synostosed midpalatal suture.
AB  - Intercanine expansion (C-C) following rapid palatal expansion is made up of
      sutural displacement (Sd-Sd), tooth tip (Tt-Tt), tooth displacement (Td-Td), and
      alveolar process tipping and bending (At+b-At+b). The involvement of these four
      components was studied on 10 rapid palatal expansion treated and two control cats
      during an active phase (25 days), a retention phase (60 days), and a relapse
      phase (60 days). The midpalatal suture was analyzed for linear measurements,
      radiopaque versus radiolucent zones and optical density from occlusal
      radiographs. Nine treated cats exhibited sutural split and one treated cat showed
      no split as a result of synostosis of the suture. The contribution of the four
      constituents [(Sd-Sd):(Tt-Tt):(Td-Td):(At+b-At+b)] to the C-C expansion changed
      from active to relapse phase from [45%:15%:25%:15%] to [50%:25%:25%:0%] in the
      animals with sutural split and from [0%:40%:60%:0%] to [0%:0%:100%:0%] in the cat
      without sutural split, implying the major role of sutural displacement in patent
      suture, and tooth displacement in synostosed suture. The latter indicates the
      potential buccal corticalis fenestration, dehiscence or perforation in synostosed
      suture undergoing RPE. In patent suture (animals with sutural split), optical
      density increased during rapid palatal expansion (soft tissue build-up) and
      decreased during retention (remineralization) and relapse phases (medial
      convergence of the palatal processes). In the animal without sutural split, a
      continuous decrease in the optical density (predetermined ossification) was
      found. The progressive six-fold surge in coefficient of variation of C-C
      expansion during the relapse phase indicates limitation in predicting rapid
      palatal expansion stability. Clinically, the use of serial occlusal radiographs
      during rapid palatal expansion is recommended to evaluate patency and extent of
      retention period.

PMID- 9598607
TI  - Alveolar and skeletal dimensions associated with lower face height.
AB  - In this study, the relationships between the lower face height and the structure
      of the frontal alveolar and basal bone were investigated. The areas and the
      dimensions of the anterior alveolar and basal midsagittal cross-sectional bone
      from the maxilla and the mandible were recorded on lateral cephalograms from 460
      untreated adults. An index was calculated dividing the sagittal by the vertical
      dimension of the midsagittal cross-sectional area. The subjects with a normal
      overbite between 0.5 and 4 mm (N=165) were divided into three groups according to
      the lower face height. A larger lower face height coincided with a larger
      maxillary alveolar and basal area and with a smaller mandibular alveolar index.
      Correlations between the lower face height and the maxillary alveolar index and
      the mandibular alveolar and basal area were low. It is concluded that long-faced
      subjects have a large mandibular alveolar height, which is more associated with a
      narrowed shape than with a large volume of the symphysis.

PMID- 9598608
TI  - Toward a perspective on orthodontic retention?
AB  - Retention is one of the most difficult challenges facing the clinician in
      orthodontics. In this article we collate current knowledge regarding the origin
      of orthodontic relapse and attempt to rationalize the necessary factors in
      planning orthodontic retention. Despite extensive research, the various elements
      leading to relapse of treated malocclusions are incompletely understood, giving
      rise to wide variation in retention protocols among clinicians. Informed consent
      with emphasis on the features of the original malocclusion and the patient's
      growth pattern, the type of treatment performed, the need for adjunctive surgical
      procedures, the type of retainer, and the duration of retention-should be
      obtained during the planning of the retention phase. True perspective on
      orthodontic retention is lacking and there is a great need for further research
      to ensure that evidence-based clinical practice is adopted in retention
      strategies.

PMID- 9598609
TI  - On the phenomenon of intraosseous migration of nonerupting teeth.
AB  - Little is know about intraosseous migration of nonerupting teeth, a rare natural
      condition of horizontal tooth movement and impaction. It occurs only in the
      mandible and involves primarily the second premolar or the canine. When the
      second premolar is the affected tooth, it always is found distal to its normal
      position. The origins of the second premolar intraosseous migration phenomenon
      are obscure and usually no treatment is recommended. Intraosseous migration
      involving the canine is commonly called transmigration because the affected
      canine moves mesially across the mandibular symphysis to the opposite side of the
      mandible. Analysis of 50 published cases of canine transmigration indicated
      higher occurrence in women and no sidedness preference. In over 80% of the
      studied cases, the canine remained nonerupted and, of the 24 cases receiving some
      treatment, all but two underwent extraction of the anomalous canine. The canine
      transmigration phenomenon appears to show signs of having some genetic
      determinants.

PMID- 9598610
TI  - Inhibition of masseteric electromyographic activity during oral respiration.
AB  - Although the effects of oral respiration on the growth and development of
      craniofacial structure have been studied previously, little is known about how
      altered respiration affects the activity of the jaw-closing muscles. Obstruction
      of the nasal airway in the cat significantly inhibited the masseteric stretch
      reflex and discharges of masseteric motor units but did not affect the
      electromyographic activity of the diaphragm. This inhibition was greater during
      inspiration than during expiration. In addition, the amplitude of the masseteric
      monosynaptic reflex elicited by electrical stimulation of the mesencephalic
      trigeminal nucleus showed no significant change in association with the altered
      respiratory mode. These findings suggest that masseteric electromyographic
      activity is inhibited during oral respiration and that the gamma-system is
      involved in this inhibition.

PMID- 9598611
TI  - Comparative study of diagnostic measures in borderline surgical cases of
      unilateral cleft lip and palate and noncleft Class III malocclusions.
AB  - Patients with complete unilateral cleft lip and palate present difficult growth
      problems. Their anteroposterior discrepancies in jaw and dentition are frequently
      so severe that some epidemiologic studies report the necessity of orthognathic
      surgery in 25% of their sample. The aims of this study were three-fold: (1) to
      delineate diagnostic measures in borderline surgical cases of unilateral cleft
      lip and palate, (2) to verify the significance of negative overjet as a measure
      of anteroposterior discrepancy, and (3) to compare these diagnostic measures with
      those of borderline surgical cases of noncleft Class III malocclusions. The
      sample consisted of 29 patients with unilateral cleft lip and palate and 25
      noncleft Class III Korean patients (mean age, 18.69 years); all had crossbites of
      all four incisors. Each of their pretreatment study casts and cephalograms were
      analyzed. The group with unilateral cleft lip and palate was divided into two
      subgroups on the basis of the method of their anterior crossbite resolution; 18
      subjects were treated with orthodontics alone (Cleft-NS) and 11 subjects with
      orthognathic surgery (Cleft-Surg). The noncleft Class III group was divided into
      two subgroups; 6 of the subjects were orthodontically treated (Cl III-NS), and 19
      were surgically treated (Cl III-Surg). The group with unilateral cleft lip and
      palate showed smaller SNA and SNB angles than the noncleft Class III group, but
      the ANB angles and the amount of anterior crossbites showed no statistical
      differences. When the Cleft-NS and the Cleft-Surg groups were compared, the ANB
      angle and the Wits measurements were significantly different. When the Cl III-NS
      and Cl III-Surg groups were compared, the SNB, ANB, L1GoGn, Wits, and the
      crossbite showed significant differences. For borderline surgical Class III
      unilateral cleft lip and palate cases, ANB angle, Wits appraisal, and ABGoGn
      angle were critical diagnostic parameters. On the other hand, the magnitude of
      anterior crossbite, the negative overjet, was shown not to be a significant
      measure of anteroposterior discrepancy.

PMID- 9598612
TI  - Determination of Class II and Class III skeletal patterns: receiver operating
      characteristic (ROC) analysis on various cephalometric measurements.
AB  - Receiver operating characteristic analysis is an excellent method for evaluating
      and comparing the performance of diagnostic tests. The purpose of this study was
      to use the receiver operating characteristic analysis to evaluate the diagnostic
      ability of several cephalometric measurements in determining the presence of
      Class II and Class III skeletal patterns. Receiver operating characteristic
      analysis was performed on 976 cases. Fifteen cephalometric measurements were
      evaluated. A computer software program ROC ANALYZER was used to tabulate the
      areas under the curves and to perform the statistical comparison between the
      curves. The results of this study indicated that the Anteroposterior Dysplasia
      Indicator had the best diagnostic ability in identifying cases with Class II and
      Class III skeletal patterns. WITS Appraisal and Overjet were highly effective in
      diagnosing cases with Class II skeletal pattern. WITS Appraisal, Convexity, AB
      Plane Angle and Overjet also performed well in diagnosing cases with Class III
      skeletal pattern.

PMID- 9598613
TI  - On the variability of cross-sectional dimensions and torsional properties of
      rectangular nickel-titanium arch wires.
AB  - Twenty-five rectangular superelastic or conventional work-hardened nickel
      titanium alloy wires, commonly used in the 0.018-inch edgewise technique,
      supplied by seven different manufacturers, along with one braided nickel-titanium
      and two beta-titanium wires, were studied with respect to wire dimensions, edge
      bevel, and mechanical properties in longitudinal torsion at 37 degrees C. The
      wires were twisted 25 degrees and studied in deactivation, simulating application
      of torque to an individual tooth. Standard Siamese brackets. with stated slot
      heights of 0.018 inches and measured slot heights of 0.0187 inches, were used.
      Most wires were within +/-0.0005 inches of the stated dimensions, but had more
      edge bevel than previously reported for stainless steel and chrome-cobalt alloy
      wires. Variations in wire dimensions and edge bevel led to variable torsional
      (third-order) clearance. The torsional stiffness varied among manufacturers
      within the various wire sizes, this being the result of differences in actual
      cross-sectional geometry and material properties. None of the tested wires
      exhibited superelastic properties under the current conditions, and only one wire
      had a superelastic tendency.

PMID- 9598614
TI  - An experimental evaluation of effects and side effects of asymmetric face-bows in
      the light of in vivo measurements of initial tooth movements.
AB  - By using a magnetic sensing system, the translational and rotational molar
      movements under the application of various asymmetric face-bows were measured two
      dimensionally in human subjects to evaluate their primary effects and side
      effects. The asymmetric face-bow designs tested were three types of power arm
      face-bows, swivel offset face-bow, and internal hinge face-bow. Although all face
      bow designs were considered to be effective in achieving asymmetric
      distalizations of the molars, they generated lateral displacements that may lead
      to an undesirable crossbite. The swivel offset face-bow may produce unexpected
      results and its fabrication is complicated. The internal hinge face-bow is
      remarkably effective for asymmetric molar distalizations. Unfortunately, it
      causes a strong crossbite tendency on the molar to be more distalized. Therefore
      the use of the power arm face-bow is thought to be relatively recommendable
      because it showed an acceptable asymmetric effect and is easily fabricated from a
      commercially available face-bow. It is concluded that all asymmetric face-bows
      generate lateral forces as side effects as long as the force delivery system with
      a combination of an asymmetric face-bow and a neck strap or head cap is applied.
      The current study suggests a method whereby the side effect of asymmetric face
      bows can be eliminated.

PMID- 9598615
TI  - Nonsurgical treatment of the patient with vertical discrepancy.
AB  - Conventional orthodontic treatment of the patient who has excessive anterior
      facial height is difficult. Many times, the patient is presented only a surgical
      orthodontic option. However, some "orthodontics only" options are available.
      These options can generally give the patient acceptable facial balance and a good
      functional occlusion. The two keys are differential diagnosis and a carefully
      monitored force system. Conventional treatment of two patients with high angle
      facial dimension will illustrate these concepts.

PMID- 9598616
TI  - Making slides for orthodontic presentations.

PMID- 9598617
TI  - Litigation, legislation, and ethics: the long arm of the law.

PMID- 9598618
TI  - British urological surgery practice: 2. Renal, bladder and testis cancer.
AB  - OBJECTIVE: To investigate the management of urological malignancies in the United
      Kingdom. METHODS: A postal survey of consultant urologists and general surgeons
      with an interest in urology was conducted to examine current clinical practice in
      urological malignancies. RESULTS: Completed questionnaires were received from 273
      consultant surgeons who saw an estimated total of 13241 new patients with renal,
      bladder or testis cancer per year; 82% had access to on-site oncology services
      and in general there was a consensus in the answers given. Most respondents
      advised active treatment of an asymptomatic primary renal cancer in the presence
      of metastases and a significant proportion of patients with metastases were not
      prescribed immunotherapy nor were offered a multidisciplinary approach for their
      condition. Forty-six per cent of patients with testis cancer received no advice
      to store sperm before chemotherapy and there were varied opinions as to the need
      for surgical resection of residual masses after completion of chemotherapy.
      CONCLUSION: This survey showed minor variations in the management of renal,
      bladder and testis tumours in the UK. Consensus management guidelines for
      urological malignancies and a change in the working relationships between
      urologists and oncologists is required, to improve the outcome of patients with
      urological malignancy.

PMID- 9598619
TI  - The results of holmium laser resection of the prostate.
AB  - OBJECTIVE: To assess the results of holmium-laser resection of the prostate
      (HOLRP) in the treatment of benign prostatic hyperplasia. PATIENTS AND METHODS:
      Between 1994 and 1997, 967 patients underwent HOLRP in Tauranga, New Zealand, and
      in Derby, United Kingdom. The patients were followed at 1, 3 and 6 months after
      treatment using measurements of symptom score and urinary flow rate. RESULTS:
      There was a large and sustained improvement in symptom scores and urinary flow
      rates, with no mortality and low morbidity. CONCLUSION: We recommend this
      technique as an alternative to transurethral resection in the surgical treatment
      of bladder outlet obstruction due to benign prostatic hypertrophy.

PMID- 9598620
TI  - Transurethral resection of the prostate in the anticoagulated patient.
AB  - OBJECTIVE: To assess the safety of transurethral prostatectomy (TURP) in patients
      on long-term full anticoagulation. PATIENTS AND METHODS: Twelve TURPs were
      performed on 11 patients with urinary retention or severe symptoms from prostatic
      obstruction who also required anticoagulation for a history of life-threatening
      thromboembolic disease (seven) or prosthetic heart valves (four). Patients
      stopped taking warfarin 3 days before surgery; on admission a day later, full
      intravenous heparinization was commenced. Heparin was stopped 4 h before TURP and
      re-commenced with an initial bolus in the recovery room, and warfarin re-started
      that evening. RESULTS: The mean weight of prostate resected was 23 g and the mean
      peri-operative decrease in haemoglobin was 1.6 g/dL. Only one patient required a
      transfusion of 3 units, but the activated partial thromboplastin time (APTT) had
      risen to >4. The mean pre- and post-operative APTT were 1.7 and 2.64,
      respectively, and the mean total length of hospital stay 6.7 days. Three patients
      were re-admitted for secondary haemorrhage at 8, 9 and 28 days after TURP, but
      all resolved with catheterization for 24 h only. There were no other major
      complications or thrombo-embolic phenomena. CONCLUSION: TURP can be conducted
      safely in this high-risk group of patients with a regimen that allows a brief but
      controlled interruption to their full anticoagulation. This protects from the
      risks of thromboembolic incidents with no major increase in haemorrhage or
      hospital stay.

PMID- 9598621
TI  - Prostate-specific membrane antigen.

PMID- 9598623
TI  - Free-to-total prostate-specific antigen (PSA) ratio improves the specificity for
      detecting prostate cancer in patients with prostatism and intermediate PSA
      levels.
AB  - OBJECTIVE: To investigate the clinical significance of the free-to-total prostate
      specific antigen (PSA) ratio in improving the specificity of PSA measurement for
      detecting prostate cancer within the diagnostic intermediate range (4-10 ng/mL
      total PSA) in patients referred for the treatment of urinary symptoms. PATIENTS
      AND METHODS: Serum samples were obtained from 333 consecutive patients with
      obstructive and irritative urinary symptoms. Of these men, 114 had total PSA
      levels of 4-10 ng/mL; 22 had prostate cancer (group 1) and 71 had benign
      prostatic hyperplasia (BPH, group 2). Group 3 consisted of 21 patients with BPH
      and a chronic indwelling catheter. The concentrations of free and total PSA
      (ProStatus, Wallac Oy, Turku, Finland) and PSA complexed to alpha-1
      antichymotrypsin were measured and the free-to-total PSA ratio calculated. All
      patients under 70 years of age or with suspicious findings on digital rectal
      examination or transrectal ultrasonography underwent ultrasound-guided sextant
      prostate biopsies. Of the 114 patients, 105 (92%) underwent transurethral
      resection of the prostate and six (5%) radical retropubic prostatectomy. RESULTS:
      Patients in group 1 had significantly lower median free PSA concentrations (0.78
      ng/mL vs 1.13 ng/mL, P < 0.001) and a lower free-to-total PSA ratio (12.1% vs
      19.9%, P < 0.001) than those in group 2. The differences were similar between
      group 1 and group 3 (median free PSA in group 3, 1.06 ng/mL, P = 0.03, and free
      to-total PSA ratio 18.7%, P = 0.007). There were no significant differences
      between patients in groups 2 and 3. The free-to-total PSA ratio had a higher
      specificity than total PSA at all sensitivity levels, e.g. a threshold free-to
      total PSA ratio of 0.20 detected 91% of cancers and spared 48% (group 2) or 46%
      (group 3) from unnecessary biopsies. The area under the receiver operating
      characteristic curve for group 1 vs group 2 was 0.56 (total PSA) and 0.78 (free
      to-total PSA ratio) and for group 1 vs group 3 was 0.56 (total PSA) and 0.81
      (free-to-total PSA ratio). CONCLUSION: In those patients with extensive symptoms
      from BPH and requiring surgical treatment, the free-to-total PSA ratio improves
      the specificity for detecting prostate cancer in the diagnostic 'grey zone' of 4
      10 ng/mL total PSA. This improvement occurred in patients with or without a
      chronic indwelling catheter for urinary retention.

PMID- 9598622
TI  - Prophylaxis for transrectal prostatic biopsies: a randomized controlled study of
      intravenous co-amoxiclav given as a single dose compared with an intravenous dose
      followed by oral co-amoxiclav for 24 h.
AB  - OBJECTIVE: To compare in a randomized prospective study the infective
      complication rates of a single intravenous dose of co-amoxiclav given alone
      before transrectal prostatic biopsy with an intravenous dose followed by oral co
      amoxiclav for 24 h. PATIENTS AND METHODS: Eighty-three patients undergoing
      prostatic biopsy were randomized to receive 1.2 g co-amoxiclav intravenously and
      then either three further doses of oral co-amoxiclav (Group 1) or no further
      antibiotics (Group 2). The evaluation included analysis of a mid-stream urine
      (MSU) sample before and 72 h after biopsy, and the recording of oral temperatures
      and symptoms in the first 44 patients. Patients with symptomatic urinary tract
      infections (UTIs), prostatitis, indwelling catheters, diabetes and those
      receiving steroid therapy were excluded. RESULTS: Eight patients, four from each
      treatment arm, were found to have asymptomatic UTIs from their MSU before biopsy.
      Excluding these patients, four patients (11%) from Group 1 and six from Group 2
      (16%) had positive MSUs at 72 h; two patients from Group 2 and one from Group 1
      required admission to hospital. Of the patients returning symptom and temperature
      charts, a further six (14%; three from each group) reported signs and symptoms
      suggestive of infection despite negative urine cultures. CONCLUSIONS: There was
      no statistically significant difference in the rate of positive MSUs between the
      groups. The incidence of infections was considerably higher than in previously
      published series where other antibiotics were used, suggesting that co-amoxiclav
      is not the drug of choice for transrectal prostatic biopsy.

PMID- 9598624
TI  - Urodynamic findings in patients with urogenital fistulae.
AB  - OBJECTIVE: To assess the feasibility of carrying out a urodynamic investigation
      in patients with a urogenital fistula and to establish the incidence of abnormal
      lower urinary tract function in such patients. PATIENTS AND METHODS: Of 38
      patients referred within the last 3 years with a diagnosis of lower urinary tract
      genital fistula, 30 were investigated by dual-channel subtracted cystometry
      before surgical treatment of their fistula; in addition, urethral pressure
      profilometry was carried out in 19 patients. Fourteen of the patients had
      fistulae into the vaginal vault; the urodynamic findings in this subgroup were
      compared with those of 12 patients with bladder neck and urethrovaginal fistulae.
      Twenty-six of the 30 patients underwent surgical treatment and 24 (92%) were
      cured anatomically by their first procedure. Ten patients complained of residual
      lower urinary tract symptoms and were re-investigated. RESULTS: Of the 38
      patients, 47% had genuine stress incontinence, 40% showed systolic detrusor
      instability and 17% impaired bladder compliance. Half had evidence of voiding
      dysfunction; most appeared to be of a hypotonic detrusor type, although four
      cases showed an obstructive pattern. Fifteen patients had more than one
      abnormality and only five (17%) had entirely normal urodynamic findings. The
      overall incidence of functional abnormality was highest in the patients with
      urethral or bladder neck fistulae, with only one showing entirely normal
      urodynamic findings. Genuine stress incontinence was found more than twice as
      often associated with urethral or bladder neck fistulae and detrusor instability
      was also more common in this group. Voiding dysfunction of both hypotonic and
      obstructive types was found equally in the two groups. After surgical treatment,
      most patients became continent and free from lower urinary tract symptoms,
      although one complained of residual stress incontinence and nine of urgency or
      urge incontinence. Of the latter, six were found to have detrusor instability,
      one after repair of vault fistula, three after urethral or bladder neck fistulae
      and the other two after mid-vaginal fistulae. CONCLUSION: There is a high
      incidence of abnormal lower urinary tract function in patients with urogenital
      fistulae. Patients with urethral or bladder neck fistulae had a higher incidence
      of both detrusor instability and genuine stress incontinence than those with
      fistulae into the vaginal vault. Many of these abnormalities appear to resolve
      after successful repair of the fistula, although detrusor instability may persist
      and require further treatment in some women. These findings are relevant to the
      counselling of patients before repair and may be of medico-legal significance.

PMID- 9598625
TI  - Urological complications of bladder-drained pancreatic allografts.
AB  - OBJECTIVE: To examine the spectrum of urological complications associated with
      bladder drainage of pancreatic allografts. PATIENTS AND METHOD: Between July 1991
      and October 1996, 140 consecutive bladder-drained pancreatic allografts were
      performed and were reviewed retrospectively to determine the spectrum of post
      operative urological complications. Ninety-five patients (68%) underwent
      simultaneous pancreas-kidney transplantation, 35 (25%) had the pancreas
      transplanted after the kidney, while 10 (7%) had a pancreas transplant alone. The
      mean follow-up was 35 months. RESULTS: Seventy patients (50%) had urological
      complications necessitating intervention: 17 (12%) had retained foreign bodies,
      bladder tumours occurred in three, 14 had bladder calculi and 15 (11%) had
      cystoscopic evidence of duodenitis. One patient developed an arteriovenous
      fistula and one had a necrotic duodenal allograft. Reflux pancreatitis occurred
      in six patients. Other complications included urethral stricture (three),
      urethral erosion (three), epididymitis (three), acute prostatitis (one) and
      prostatic abscess (one). One patient developed a urethrocutaneous fistula and
      another developed a vesicocutaneous fistula. In the series, 30 of the 140
      patients (21%) required eventual conversion to enteric drainage of their
      allograft as definitive therapy. CONCLUSIONS: Pancreatic transplantation with
      bladder drainage is associated with a wide range of significant urological
      problems. Although appropriate treatment can resolve most of the complications,
      this often entails additional operative intervention, which may increase the long
      term morbidity or jeopardize graft function. As a result of the severity of these
      urological complications, some centres use primary enteric drainage as the method
      of choice for pancreatic transplantation.

PMID- 9598626
TI  - Functional rat bladder regeneration through xenotransplantation of the bladder
      acellular matrix graft.
AB  - OBJECTIVE: To determine the decreased antigenicity of the bladder acellular
      matrix graft (BAMG) through xenotransplantation and to assess the in vivo and in
      vitro functional properties of the rat urinary bladder thus regenerated.
      MATERIALS AND METHODS: After partial cystectomy (> 50%), BAMGs prepared from
      hamster, rabbit and dog urinary bladders were grafted to male and female Sprague
      Dawley rats; 10 control rats underwent partial cystectomy only. Urinary storage
      and voiding function were monitored in 15 animals using a specially designed
      'micturition cage' and cystometry. After 4 months, organ-bath studies and
      histological techniques were used to evaluate bladder regeneration in vitro in
      the grafted animals. RESULTS: Clinically relevant antigenicity was not evident;
      no animal died from rejection and all bladder wall components regenerated in all
      BAMG xenografts. However, the degree and quality of regeneration varied.
      Muscularization, peak pressure, and bladder capacity were higher in the hamster
      BAMG-grafted animals, whereas in vitro contractility and compliance were best in
      the dog BAMG-regenerated bladders. All grafted bladders had significantly better
      capacity and compliance than the autoregenerated bladders after partial
      cystectomy alone. CONCLUSIONS: The present in vivo and in vitro studies show that
      BAMG-augmentation cystoplasty can lead to morphological and functional
      regeneration of the rat bladder, preserving its low-pressure reservoir function.
      Because BAMG-regenerated bladders show functional innervation that is similar to
      normal bladders, they can work in coordination with the host bladder components,
      thus generating adequate intravesical pressure to produce sustained voiding. The
      decreased antigenicity makes heterologous BAMG transplants feasible without
      immunosuppression.

PMID- 9598627
TI  - Transcutaneous electrical stimulation of thigh muscles in the treatment of
      detrusor overactivity.
AB  - OBJECTIVE: To investigate the clinical effects on detrusor overactivity of a new
      method of transcutaneous reciprocal electrical stimulation of the thigh muscles.
      PATIENTS AND METHODS: Nineteen patients with detrusor overactivity, comprising 14
      with detrusor hyperreflexia (DH) and five with idiopathic detrusor instability
      (IDI), were studied. Electrical stimulation was applied alternately to the
      quadriceps and hamstring muscles of one or both legs through surface electrodes
      for 20 min. The treatment was given once a day for 14 days and then the patients
      were evaluated urodynamically. RESULTS: All 19 patients tolerated the therapy
      well and none reported any adverse effects. The mean maximum cystometric capacity
      increased significantly (P < 0.05) after treatment. In 11 of the 19 patients, the
      maximum cystometric capacity was increased by > 50% of the pretreatment value;
      this occurred in eight of 14 of those with DH and in three of five of those with
      IDI. In six of the 11 who responded in this way, there was a clinical improvement
      in their urinary incontinence and frequency for several weeks to 3 months after
      the period of therapy. A second 14-day treatment was also effective in all four
      patients who underwent a repeat trial. CONCLUSION: This method of transcutaneous
      electrical stimulation can inhibit DH as well as IDI with no adverse effects. The
      suppressive effect on detrusor overactivity may persist for several months and
      repeat trials appear to be effective. Thus, we believe that this new stimulation
      technique should be tried as an alternative to other types of electrical
      stimulation and augmentation cystoplasty.

PMID- 9598628
TI  - Bowel motility after enterocystoplasty.
AB  - OBJECTIVE: To determine whether the distension of bowel-augmented bladders during
      filling and urine storage stimulates gastrointestinal peristalsis, resulting in
      diarrhoea and increased bowel frequency. PATIENTS AND METHODS: Five patients with
      symptomatic diarrhoea occurring after enterocystoplasty were studied; all had
      undergone bladder augmentation using ileum or colon at least 6 months previously.
      Using bowel frequency charts and colonic transit-time studies, their bowel
      function was assessed over 6 days while patients self-catheterized 4-hourly. This
      was repeated when the patient's bladders were decompressed with an indwelling
      catheter, and the results before and after bladder decompression compared.
      RESULTS: One patient showed a significant increase in colonic transit time, from
      44.4 to 57.6 h, a decrease in the percentage of liquid motions from 50% to 42.8%
      and a corresponding small decrease in bowel frequency with bladder decompression.
      One patient reported an increase in liquid stools, but there was a minor decrease
      in colonic transit time. The remaining three patients showed no improvement with
      bladder decompression. When data were combined and analysed using Student's
      paired t-test, there were no significant changes in colonic transit time, bowel
      frequency and diarrhoea stools with bladder decompression. CONCLUSIONS:
      Eliminating bladder distension and hence distension of the incorporated bowel
      segment in reconstructed bladders has no impact on bowel motility.

PMID- 9598629
TI  - Long-term results and complications of augmentation ileocystoplasty for
      idiopathic urge incontinence in women.
AB  - OBJECTIVE: To assess the long-term (3-9 years) results of augmentation
      ileocystoplasty for non-neurogenic female urge incontinence in terms of
      continence, the need for intermittent self-catheterization and the need for
      additional or auxiliary treatment, to define the long-term complications and to
      assess the patients' satisfaction with the outcome. PATIENTS AND METHODS: The
      study comprised 51 women who underwent augmentation ileocystoplasty for non
      neurogenic urge incontinence between November 1987 and December 1993; 27 patients
      had associated interstitial cystitis. All patients had exhausted conservative
      methods, with an unsatisfactory outcome. All patients were interviewed about the
      results of the procedure, and their charts reviewed and updated with relevant
      information. RESULTS: Within a mean (range) follow-up of 75.4 (36-109) months, 27
      patients (53%) were completely continent, 13 (25%) had occasional leaks and nine
      (18%) continued to have disabling urge incontinence frequently requiring pads.
      Regular self-catheterization was needed by 20 (39%) patients while the rest
      emptied adequately with no or minimal residual volumes. Additional
      pharmacotherapy had to be used by 12 (24%) patients. Three patients later
      developed stress urinary incontinence and were managed with fascial sling
      procedures. The patch was revised in two patients and excised from four others
      because they had high residual volumes and uncontrollable infections. Two
      patients had an ileal conduit diversion for persistent incontinence. The most
      common complication was recurrent urinary tract infections, seen in 22 patients
      using intermittent self-catheterization. Mucus retention occurred regularly in 10
      patients, six had chronic diarrhoea, four had latent bowel obstruction, one
      developed a bladder stone, one an incisional hernia and one developed patch
      necrosis and perforation. Twenty-seven patients (53%) were happy with the outcome
      of the procedure while 20 (39%) were not; four patients were unsure whether a
      change had occurred. CONCLUSION: Augmentation ileocystoplasty is a valuable
      alternative for women with intractable urge incontinence. However, these patients
      and their physicians should be aware of its limitations, specifically the
      possibility that incontinence may persist and the high probability of the need
      for self-catheterization, with potential subsequent urinary tract infection.

PMID- 9598630
TI  - Comparing neural networks in the discrimination of benign from malignant lower
      urinary tract lesions.
AB  - OBJECTIVE: To compare the performance of two different neural networks (NNs) in
      the discrimination of benign and malignant lower urinary tract lesions. MATERIALS
      AND METHODS: A group of patients was evaluated, comprising 50 cases of lithiasis,
      61 of inflammation, 99 of benign prostatic hyperplasia (BPH), five of in situ
      carcinoma, 71 of grade I transitional cell carcinoma of the bladder (TCCB), and
      184 of grade II and grade III TCCB. Images of routinely processed voided urine
      smears were stained using the Giemsa technique and analysed using an image
      analysis system, providing a dataset of 45452 cells. Two NN models of the back
      propagation (BP) and learning vector quantizer (LVQ) type were used to
      discriminate benign from malignant cells and lesions, based on morphometric and
      textural features. The data from 13636 randomly selected cells (30% of the total
      data) were used as a training set and data from the remaining 31816 cells
      comprised the test set. Similarly, in an attempt to discriminate patients, 30% of
      the cases, selected randomly, were used to train a BP and an LVQ NN, with the
      remaining 329 cases used for the test set. The data used for training and testing
      were the same for the two kinds of classifiers. RESULTS: The two NNs gave similar
      results, with an overall accuracy of discrimination of approximately 90.5% at the
      cellular level and of approximately 97% for individual patients. There were no
      statistically significant differences between the two NNs at the cellular or
      patient level. CONCLUSIONS: The use of NNs and image morphometry could increase
      the diagnostic accuracy of voided urine cytology; despite the different nature of
      the two classifiers, the results obtained were very similar.

PMID- 9598631
TI  - The vesico-ureteric junction in three cases of primary obstructive megaureter
      associated with ectopic ureteric insertion.
AB  - OBJECTIVE: To examine the histological structure and autonomic innervation of the
      vesico-ureteric junction (VUJ) in three cases of primary obstructive megaureter
      occurring in association with ectopic ureteric insertion. PATIENTS AND METHODS:
      Specimens of VUJ were obtained from one male and two females with primary
      obstructive megaureter and ectopic ureteric insertions. Serial frozen sections
      were cut and stained with either Masson's trichrome or immunostained for protein
      gene product (PGP 9.5; a general nerve marker) or dopamine beta-hydroxylase
      (DbetaH), a marker for noradrenergic nerves. RESULTS: In each case examined the
      terminal ureter was encircled by a thick collar of smooth muscle on the inside of
      which lay normal narrow-diameter longitudinally orientated ureteric muscle
      bundles. Loose connective tissue separated the surrounding detrusor muscle from
      this abnormal muscle collar, which was formed of distinctive smooth muscle cells
      arranged in a meshwork. The autonomic innervation of the ureteric and detrusor
      muscle bundles was similar to that previously reported for the normal VUJ while
      the thick muscle collar was richly innervated by DbetaH-immunoreactive
      noradrenergic nerves. CONCLUSION: The presence of an additional smooth muscle
      collar surrounding the terminal ureter may impede the normal flow of urine from
      ureter to bladder and be the cause of megaureter in these patients. We propose
      that the presence of this muscular collar arises from the developmental anomaly
      and suggest that these cases represent a subgroup that requires early surgical
      treatment.

PMID- 9598632
TI  - Microvessel density as a prognostic marker for transitional cell carcinoma of the
      bladder.
AB  - OBJECTIVE: To investigate the prognostic significance of mean vascular density
      (MVD) in a variety of transitional cell carcinomas (TCC) obtained by biopsy and
      cystectomy, and thus determine the importance of vascular density as a prognostic
      indicator for vesical TCC. PATIENTS AND METHODS: Tumour vasculature was
      visualized using factor VIII immunohistochemistry. The MVDs of tumours from 42
      cystectomy specimens were correlated with patient survival over a maximum follow
      up of 156 months. The results were also compared with those obtained from initial
      bladder biopsy in a subset of 29 patients. RESULTS: Twenty-five patients had died
      over a mean follow-up of 32 months. The MVDs from cystectomy specimens ranged
      from 29 to 229 vessels per medium-power field (0.94 mm2) while that for biopsies
      before cystectomy ranged from 51 to 155 vessels. The MVD for both cystectomy and
      biopsy specimens showed a significant association with survival, but this was
      absent in a multivariate analysis that included tumour stage and grade, and there
      was a poor correlation between the MVD of cystectomy- and biopsy-derived tumours.
      CONCLUSION: The assessment of tumour vascularity appears to be of little clinical
      importance for vesical TCC.

PMID- 9598633
TI  - The use of penile prostheses in the treatment of impotence.

PMID- 9598634
TI  - New developments in self-injection therapy for erectile dysfunction.

PMID- 9598636
TI  - Frozen-thawed epididymal sperm is effective for intracytoplasmic sperm injection:
      implications for the urologist.
AB  - OBJECTIVE: To evaluate the pregnancy potential of frozen-thawed surgically
      retrieved epididymal sperm when used with intracytoplasmic sperm injection
      (ICSI). PATIENTS AND METHODS: From August 1994 to January 1997, 20 thawed samples
      of sperm from 19 patients, surgically retrieved and frozen after percutaneous or
      open epididymal aspiration, were used for ICSI. The results were compared with
      those obtained using fresh sperm obtained at the same procedure. RESULTS: Of the
      specimens of surgically retrieved sperm which had been frozen, stored and thawed,
      15 had sufficient motile sperm for use with ICSI. The fertilization, cleavage and
      pregnancy rates in those cycles were similar to the same couples' previous cycle
      using fresh sperm from the same collection and to the overall results in the
      NURTURE ICSI programme obtained with fresh epididymal sperm. CONCLUSION: Scrotal
      exploration for diagnostic testicular biopsy and/or reconstructive surgery
      without having access to sperm-freezing and storage facilities could represent a
      lost opportunity for the patient.

PMID- 9598635
TI  - The role of colour Doppler imaging in the management of Peyronie's disease.
AB  - OBJECTIVE: To determine the role of colour Doppler imaging (CDI) in the
      investigation of erectile dysfunction in patients with Peyronie's disease.
      PATIENTS AND METHODS: Fifty consecutive patients (age 35-75 years) with
      Peyronie's disease who were considered suitable for surgical treatment were
      investigated using CDI to determine the haemodynamic variables of penile
      vasculature after an intracorporeal injection of 20 microg of alprostadil (with
      manual self-stimulation). A clinician independently recorded the quality of
      erection and the deformity. RESULTS: Twenty of 50 patients (40%) considered they
      had normal erectile function despite their penile deformity and all had normal
      responses, although they tended to exaggerate the degree of penile deformity. Of
      the 30 remaining patients, 21 who considered themselves to have erectile
      dysfunction had normal clinical and CDI haemodynamic responses to alprostadil.
      The remaining nine patients had a variety of erectile problems and whilst CDI
      showed altered haemodynamic values, in no case did CDI alter the proposed
      treatment based on the clinically apparent features of those patients.
      CONCLUSION: Colour Doppler imaging of the penis after pharmacologically induced
      erection gives anatomical and functional information in patients with Peyronie's
      disease but does not provide useful additional information to aid the selection
      of surgical treatment for the disease.

PMID- 9598637
TI  - Does incision of the tunica vaginalis during the Palomo procedure prevent post
      operative hydrocele?
AB  - OBJECTIVE: To assess whether incision of the tunica vaginalis of the ipsilateral
      testis during the Palomo procedure affects the incidence of post-operative
      hydrocele. PATIENTS AND METHODS: Forty-two patients with varicocele were treated
      between 1992 and 1996, all undergoing the Palomo procedure. In 15 patients,
      incision of the tunica vaginalis of the ipsilateral testis was performed with the
      Palomo procedure, to prevent the formation of hydrocele. All patients were
      followed at regular intervals, for 3 months to 4 years. RESULTS: Of 27 patients
      who underwent the Palomo procedure alone, four developed post-operative hydrocele
      requiring operation. None of those who underwent incision of the tunica vaginalis
      with the Palomo procedure developed a hydrocele. The duration of hospital stay
      was the same in both groups (mean 2.5 days). During the follow-up, there was no
      difference in the size of the testes, as assessed with the Prader orchidometer,
      between the two groups. CONCLUSION: Incision of the tunica vaginalis of the
      ipsilateral testis in addition to the Palomo procedure prevents the development
      of post-operative hydrocele and causes no adverse sequelae.

PMID- 9598638
TI  - Correlation between genito-urinary anomalies, semen analysis and CFTR genotype in
      patients with congenital bilateral absence of the vas deferens.
AB  - OBJECTIVE: To evaluate the incidence of renal and seminal vesicle (SV)
      abnormalities, and the presence or absence of CFTR gene mutations, in a cohort of
      patients referred for congenital bilateral absence of the vas deferens (CBAVD).
      PATIENTS AND METHOD: Forty-one patients with CBAVD, confirmed by surgical
      exploration, were evaluated by ultrasonography for renal and SV anomalies. Semen
      variables (pH, fructose level and ejaculate volume), sweat chloride levels and
      mutations of the 3, 4, 7, 9, 10, 11, 13, 14b, 17b, 19, 20 and 21 exons of the
      CFTR gene were determined. RESULT: In eight patients with renal anomalies there
      were no detectable mutations of CFTR, compared with 23 in the 33 patients with no
      renal anomalies (P < 0.02). SV anomalies were not related to the presence or
      absence of mutations (11 of 23 vs 11 of 18), or in compound heterozygote patients
      carrying two mutations (eight of 13 vs three of 10). Semen variables (pH < 7.2,
      fructose < 1 g/L and ejaculate volume < 2 mL) did not differentiate patients with
      or without anomalies of the kidney, SV or with mutations, except in patients with
      a pH < 7.2 for which renal anomalies were less frequent (two of 25 vs six of 16,
      P < 0.05) and mutations more frequent (19 of 25 vs five of 12, P < 0.01).
      CONCLUSION: Renal anomalies associated with CBAVD should be considered as
      supporting maldevelopment as a cause, but analysis of CFTR mutations in these
      cases should not be omitted. Unlike anomalies of the SV, a low ejaculate volume
      or low fructose level, a semen pH of < 7.2 is the only nonspecific variable in
      patients with CFTR mutations.

PMID- 9598639
TI  - Estimating the depth of puncture in percutaneous nephrolithotomy: an alternative
      approach.

PMID- 9598640
TI  - Removal of a detached resectoscope insulating beak from the bladder.

PMID- 9598641
TI  - Orthotopic bladder substitution by detubularized sigmoid using a new method of
      neovesico-urethral anastomosis.

PMID- 9598642
TI  - Vasovasostomy using albumisol solder with an argon laser.

PMID- 9598643
TI  - Pledgeted sutures for parenchymal compression facilitate partial nephrectomy.

PMID- 9598644
TI  - Acute-angle closure glaucoma as a side-effect of oxybutynin.

PMID- 9598645
TI  - Giant hydrocele of the canal of Nuck.

PMID- 9598646
TI  - Mesonephric carcinoma arising from a female urethral diverticulum.

PMID- 9598648
TI  - Observations on the uninhibited bladder of the common wombat.

PMID- 9598647
TI  - Upper renal tract deterioration after cyclophosphamide-induced cystitis: the case
      for monitoring after cyclophosphamide therapy.

PMID- 9598649
TI  - Extraction by extracorporeal shock wave lithotripsy of a forgotten ureteric stent
      after cystectomy.

PMID- 9598651
TI  - A double vas deferens.

PMID- 9598650
TI  - Gross calcification within the prostate gland.

PMID- 9598652
TI  - The growing teratoma syndrome: an unusual case.

PMID- 9598653
TI  - The testicular 'tumour' of adrenogenital syndrome: an unusual cause of male
      infertility.

PMID- 9598654
TI  - Leydig cell tumour of the testis: a rare cause of male infertility.

PMID- 9598655
TI  - Recurrent intravesical foreign bodies.

PMID- 9598657
TI  - Significantly increased complication risks with mass circumcisions.

PMID- 9598656
TI  - The use of salivary stimulant pastilles to improve compliance in women taking
      oxybutinin hydrochloride for detrusor instability.

PMID- 9598659
TI  - Seromuscular myotomy to help eversion of an urostomy.

PMID- 9598658
TI  - Transurethral resection or electrovaporization in the treatment of BPH.

PMID- 9598660
TI  - Irrigating fluids in endoscopic surgery: why glycine!

PMID- 9598661
TI  - Clinical uroselectivity: evidence from patients treated with slow release
      alfuzosin for symptomatic benign prostatic obstruction.

PMID- 9598662
TI  - Quality of life assessment in patients after laser prostatectomy.

PMID- 9598663
TI  - From mutilation to medication: the history of orchidectomy. Orchidectomy in
      ancient China.

PMID- 9598664
TI  - Squamous cell carcinoma arising in a paraurethral cyst.

PMID- 9598666
TI  - The penile disassembly technique in hypospadias repair.

PMID- 9598665
TI  - Primary amyloidosis of the urinary bladder and ureters.

PMID- 9598667
TI  - Neurogenic dysphagia: the role of the neurologist.

PMID- 9598668
TI  - Continuous subcutaneous waking day apomorphine in the long term treatment of
      levodopa induced interdose dyskinesias in Parkinson's disease.
AB  - OBJECTIVES: To determine whether continuous waking day dopaminergic stimulation
      with the dopamine agonist apomorphine can reduce levodopa induced dyskinesias in
      Parkinson's disease METHODS: 19 patients with severe unpredictable refractory
      motor fluctuations and functionally disabling levodopa induced dyskinesias were
      treated with continuous subcutaneous apomorphine monotherapy for a minimum
      duration of 2.7 years RESULTS: A mean 65% reduction in dyskinetic severity and a
      mean 85% reduction in frequency and duration occurred. On discontinuing levodopa
      a concomitant reduction in off period time was also seen (35% of waking day "off"
      reduced to 10%) CONCLUSION: Continuous waking day dopaminergic stimulation with
      apomorphine reset the threshold for dyskinesias and led to a pronounced reduction
      in their frequency. Apomorphine should be considered as a less invasive
      alternative to pallidotomy or deep cerebral stimulation in controlling levodopa
      induced interdose dose dyskinesias.

PMID- 9598669
TI  - Further studies using higher doses of botulinum toxin type F for torticollis
      resistant to botulinum toxin type A.
AB  - OBJECTIVE: A previous study of botulinum toxin type F (BTX-F) treatment for
      torticollis had shown a dose of 520 MU to be effective, but for a much shorter
      duration than is usual with botulinum toxin type A (BTX-A). The objective was to
      assess the effect of a higher dose of BTX-F. METHODS: Four of the previously
      treated patients, plus an additional patient, were treated with a higher dose of
      780 MU BTX-F. All were secondary nonresponders to BTX-A due to neutralising
      antibodies. A test injection of 40 MU BTX-F was also given into the extensor
      digitorum brevis muscle (EDB), to examine the time course of the biological
      effect of the toxin electrophysiologically. Patients were followed up at two,
      four, eight, and 12 weeks. RESULTS: All patients reported subjective improvement
      lasting from seven to 11 (mean 8.6) weeks accompanied by a significant reduction
      in mean clinical severity scores at two weeks. Four patients had pain which was
      substantially reduced. The electrophysiological studies confirmed biological
      sensitivity to the toxin in all patients, showing a significant change beginning
      at two weeks and returning to baseline at 12 weeks. The time course of this
      effect paralleled roughly that of the clinical response. The four patients who
      had previously received 520 MU BTX-F reported that the response was better and
      longer in duration with 780 MU. Dysphagia was more common than reported with the
      lower dose. CONCLUSION: Better results are possible with higher doses of BTX-F
      but the duration of benefit is still shorter than with BTX-A, seemingly due to a
      shorter duration of neuromuscular junction blockade.

PMID- 9598670
TI  - Supratentorial low grade astrocytoma: prognostic factors, dedifferentiation, and
      the issue of early versus late surgery.
AB  - BACKGROUND: A retrospective study of patients with low grade astrocytoma was
      carried out because the best management of such patients remains controversial.
      Prognostic factors were identified by multivariate analysis. Special attention
      was paid to the effect of extent and timing of surgery. METHODS: Ninety patients
      with low grade astrocytoma were studied. Seventy two patients had resective
      surgery, 15 had a diagnostic biopsy only, and three patients had resective
      surgery after initial biopsy. RESULTS: Significant prognostic factors for
      survival were age, preoperative neurological condition, epilepsy as the single
      sign, extent of surgery, and histology. The extent of surgery was highly
      significant on univariate analysis (p=0.002); however, after correction for age
      and preoperative symptoms this was considerably reduced (p=0.04). A subgroup of
      30 patients with epilepsy as their single presenting symptom was identified.
      Thirteen of these patients were treated immediately after diagnosis, whereas the
      other 17 patients were initially followed up and treated only after clinical or
      radiological progression. Survival in both groups was identical (63% survival
      rate after five years) and much better than survival for the whole group (27%
      survival rate after five years). Malignant dedifferentiation was observed in 25
      (70%) of 36 patients who were reoperated, after a median period of 37 months.
      This period was 41 months for the subgroup of patients with epilepsy only and 28
      months for the remaining patients. CONCLUSIONS: Due to the retrospective nature
      of the study only restricted conclusions can be drawn. Low grade glioma with
      epilepsy as the single symptom has a much better prognosis than if accompanied by
      other symptoms. This prognosis is not influenced by the timing of surgery. It
      seems, therefore, safe to defer surgery until clinical or radiological
      progression in low grade glioma with epilepsy only.

PMID- 9598671
TI  - Gregor Johann Mendel (1822-84).

PMID- 9598672
TI  - CLOX: an executive clock drawing task.
AB  - OBJECTIVE: To describe a clock drawing task (CLOX) designed to elicit executive
      impairment and discriminate it from non-executive constructional failure.
      SUBJECTS: 90 elderly subjects were studied (45 elderly and well persons from the
      independent living apartments of a continuing care retirement community and 45
      patients with probable Alzheimer's disease). The clock drawing performance of
      elderly patients was compared with that of 62 young adult controls. METHODS:
      Subjects received the CLOX, an executive test (EXIT25), and the mini mental state
      examination (MMSE). The CLOX is divided into an unprompted task that is sensitive
      to executive control (CLOX1) and a copied version that is not (CLOX2). Between
      rater reliability (27 subjects) was high for both subtests. RESULTS: In elderly
      subjects, CLOX subscores correlated strongly with cognitive severity (CLOX1: r=
      0.83 v the EXIT25; CLOX2: r=0.85 v the MMSE). EXIT25 and MMSE scores predicted
      CLOX1 scores independently of age or education (F(4,82)=50.7, p<0.001; R2=0.71).
      The EXIT25 accounted for 68% of CLOX1 variance. Only the MMSE significantly
      contributed to CLOX2 scores (F(4,72)= 57.2, p<0.001; R2=0.74). CLOX subscales
      discriminated between patients with Alzheimer's disease and elderly controls
      (83.1% of cases correctly classified; Wilkes' lambda=0.48, p<0.001), and between
      Alzheimer's disease subgroups with and without constructional impairment (91.9%
      of cases correctly classified; Wilkes' lambda=0.31, p<0.001). CONCLUSIONS: The
      CLOX is an internally consistent measure that is easy to administer and displays
      good inter-rater reliability. It is strongly associated with cognitive test
      scores. The pattern of CLOX failures may discriminate clinical dementia
      subgroups.

PMID- 9598673
TI  - The first unprovoked, untreated seizure in childhood: a hospital based study of
      the accuracy of the diagnosis, rate of recurrence, and long term outcome after
      recurrence. Dutch study of epilepsy in childhood.
AB  - OBJECTIVE: To assess the accuracy of the diagnosis of a first unprovoked seizure
      in childhood, the recurrence rate within two years, the risk factors for
      recurrence, and the long term outcome two years after recurrence. METHODS: One
      hundred and fifty six children aged 1 month to 16 years after a first seizure,
      and 51 children with a single disputable event were followed up. The diagnosis of
      a seizure was confirmed by a panel of three child neurologists on the basis of
      predescribed diagnostic criteria. None of the children was treated after the
      first episode. RESULTS: Five children with a disputable event developed epileptic
      seizures during follow up. The diagnosis did not have to be revised in any of the
      156 children with a first seizure. The overall recurrence rate after two years
      was 54%. Significant risk factors were an epileptiform EEG (recurrence rate 71%)
      and remote symptomatic aetiology and/or mental retardation (recurrence rate 74%).
      For the 85 children with one or more recurrences, terminal remission irrespective
      of treatment two years after the first recurrence was >12 months in 50 (59%),
      <six months in 22 (26%), and six to 12 months in 11 (13%) and unknown in two
      (2%). Taking the no recurrence and recurrence groups together, a terminal
      remission of at least 12 months was present in 121 out of the 156 children (78%).
      CONCLUSIONS: The diagnosis of a first seizure can be made accurately with the
      help of strict diagnostic criteria. The use of these criteria may have
      contributed to the rather high risk of recurrence in this series. However, the
      overall prognosis for a child presenting with a single seizure is excellent, even
      if treatment with antiepileptic drugs is not immediately instituted.

PMID- 9598674
TI  - A prospective study of the early postsurgical psychiatric associations of
      epilepsy surgery.
AB  - OBJECTIVES: To examine prospectively the frequency and nature of psychiatric
      symptoms seen in patients during the first three months after temporal lobe
      surgery for chronic intractable epilepsy and in addition to study the relation
      between presurgical mental state, laterality of surgery, and postsurgical seizure
      and psychiatric course. METHOD: A consecutive series of 60 patients being
      assessed for temporal lobe surgery for intractable epilepsy were studied. They
      were interviewed before surgery and at six weeks and again at three months after
      operation. RESULTS: At six weeks after surgery half of those with no
      psychopathology preoperatively had developed symptoms of anxiety or depression
      and 45% of all patients were noted to have increased emotional lability. By three
      months after surgery emotional lability and anxiety symptoms had diminished
      whereas depressive states tended to persist. Patients with a left hemispheric
      focus were more likely to experience persisting anxiety. CONCLUSION: The early
      months after surgery for epilepsy are characterised by the relatively common
      presence of psychiatric symptoms. It is proposed that presurgical and early
      postsurgical neuropsychiatric involvement in programmes of surgery for epilepsy
      will help to improve the quality of the treatment package offered to patients.

PMID- 9598675
TI  - The prevalence of multiple sclerosis in the Leeds Health Authority.
AB  - OBJECTIVES: To determine the prevalence of multiple sclerosis in the Leeds Health
      District. METHODS: Multiple sources of case ascertainment were used-namely,
      neurology departments, hospital episode statistics, general practitioners, the
      Leeds branch of the Multiple Sclerosis Society, the West Yorkshire Multiple
      Sclerosis Therapy Centre, community physiotherapists and occupational therapists,
      the Leeds Wheelchair Centre, and the Young Disabled Unit. Data collection was
      from retrospective analysis of hospital and primary care case records. A
      population based incidence register was established by prospectively registering
      all new patients with diagnoses of multiple sclerosis. RESULTS: On prevalence
      day, 30 April 1996, 712 people with multiple sclerosis were identified living in
      Leeds (population 732,061), giving a prevalence of 97/10(5). The prevalence for
      definite and probable multiple sclerosis was 84/10(5), and for suspected multiple
      sclerosis it was 13/10(5). The sex ratio of prevalent people with multiple
      sclerosis was 2.79 to 1 women to men. The mean age of prevalent cases was 51
      years, the mean age at symptom onset was 34 years, and the mean duration of
      disease was 16 years. Forty cases were prospectively reported as incident cases
      from 1 November 1995 to 1 February 1996. CONCLUSIONS: The prevalence of multiple
      sclerosis in Leeds was found to be similar to that in the south of the United
      Kingdom but lower than that in Scotland. There is no evidence of a latitudinal
      gradient of increasing prevalence of multiple sclerosis from the south to the
      north of England.

PMID- 9598677
TI  - Investigating individual subjects and screening populations for asymptomatic
      carotid stenosis can be harmful.
AB  - OBJECTIVES: Trials suggesting that carotid endarterectomy in individual subjects
      with asymptomatic carotid stenosis reduces stroke risk have led to calls for
      screening. This study aimed to determine which groups might be harmed and which
      might benefit from a screening programme, and also to identify which individual
      subjects identified as positive for severe asymptomatic stenosis by carotid
      ultrasound are appropriate to put forward for further tests or procedures.
      METHODS: A probability model was used to estimate the outcomes of three screening
      strategies: carotid ultrasound followed by catheter angiography, or by magnetic
      resonance angiography (MRA), or ultrasound alone, followed by carotid
      endarterectomy if severe stenosis is detected. Information from the current
      literature was used to estimate sensitivity and specificity of ultrasound and
      MRA, risks of angiography and endarterectomy, and risk reduction after surgery
      for severe stenosis. For each strategy over a range of possible prevalences of
      severe asymptomatic stenosis, overall benefit to harm ratio was calculated, and
      number of strokes or deaths prevented or caused per 10,000 subjects screened.
      RESULTS: At the prevalence of carotid stenosis found in the general population
      (<1%) screening will cause more strokes than it prevents, even using the most
      optimistic published figures. Only at prevalences of over 20% are significant
      benefits seen, and then only in centres with high test sensitivity and
      specificity and very low angiographic and surgical risk. Groups with such a high
      prevalence have not yet been reliably identified. Screening individual subjects
      from high prevalence groups would have limited public health impact, with at best
      about 100 strokes prevented for every 10,000 screened at 20% prevalence.
      CONCLUSIONS: Investigating asymptomatic individual subjects for carotid stenosis
      may be harmful except in high prevalence groups. There is insufficient
      information about which these groups are, and at present screening cannot be
      recommended. Acting on a positive carotid ultrasound test in individual subjects

PMID- 9598676
TI  - Cortical brain microdialysis and temperature monitoring during hypothermic
      circulatory arrest in humans.
AB  - OBJECTIVES: Critical vascular surgery of the brain or the heart occasionally
      requires total cessation of the circulatory system. Profound hypothermia is used
      to protect the brain from ischaemic injury. This study explores the use of
      microdialysis to measure metabolic indices of ischaemia: glutamate, lactate, and
      pH, and cerebral temperature during profound hypothermia and circulatory arrest.
      METHODS: Effluent from a microdialysis catheter placed in the cerebral cortex of
      three patients undergoing complete circulatory arrest was continuously sampled.
      Samples were pooled over 10 minute periods and glutamate and lactate
      concentrations were measured postoperatively. Brain temperature and pH were
      measured on line intraoperatively. Electroencephalography and monitoring of
      somatosensory evoked potentials and brainstem auditory evoked potentials were
      simultaneously carried out. RESULTS: Patient 1 had normal glutamate and lactate.
      PH was 6.75 to 6.85 and increased to 6.9 after warming ensued. Patient 2 had
      raised glutamate and lactate during most measurements. The glutamate
      concentrations peaked at 305 microM/l at the start of the measurements and fell
      below 20 microM/l after warming. The lactate concentrations peaked at 680
      microM/l before cooling, rose to 1040 microM/l during the cooling process,
      decreased to 212 microM/l during circulatory arrest, and rose again to 620
      microM/l after warming. The pH started at 7.06 and continued a downward course
      until stabilising at a pH of 6.5 after circulatory arrest. Patient 3 had a
      transient, mild increase in glutamate and lactate during the cooling and warming
      period. pH was stable throughout. CONCLUSION: Microdialysis combined with
      temperature and pH measurements of the cerebral cortex promises to be an
      important tool in detecting cerebral ischaemia. Further studies are needed to
      validate our findings and test the feasibility of modifying ischaemic changes.

PMID- 9598678
TI  - Early transoesophageal echocardiography in cryptogenic and lacunar stroke and
      transient ischaemic attack.
AB  - OBJECTIVES: To test the hypothesis that transoesophageal echocardiography (TOE)
      carried out within three days of a first stroke or transient ischaemic attack of
      cryptogenic or lacunar type may disclose more thrombi or spontaneous echo
      contrast (SEC) than previously reported. This finding may help early treatment
      decisions. METHODS: Patients aged between 40 and 80 years, admitted for transient
      ischaemic attack or ischaemic stroke during a 40 month period, were prospectively
      considered. TOE was carried out within 72 hours of symptom onset with a 5 MHz
      biplanar transducer. Subjects with recurring events, very severe strokes, large
      artery obstructions, or obvious cardiac sources of embolism were excluded.
      RESULTS: Sixty five patients were studied, 43 with a cryptogenic stroke or
      transient ischaemic attack (66.2%), and 22 with a lacunar stroke (33.8%). The
      mean (SD) interval between symptom onset and TOE was 43.4 (17.2) hours for
      cryptogenic, and 48.5 (19.5) hours for lacunar patients. Atrial thrombi were
      found in one patient with a cryptogenic stroke (2.32% of cryptogenic events; 95%
      confidence interval 0.06-12.29), whereas SEC was found in five patients (7.7%
      overall), two with a lacunar and three with a cryptogenic stroke. CONCLUSIONS: An
      early TOE does not seem to increase substantially the detection of atrial thrombi
      or SEC in patients with a first stroke or transient ischaemic attack of
      cryptogenic or lacunar nature. Therefore, this examination can be carried out
      when the patients' conditions are stable, and without overloading the
      cardiovascular laboratory daily schedule.

PMID- 9598679
TI  - Does spasticity contribute to walking dysfunction after stroke?
AB  - OBJECTIVES: Clinically, it is assumed that spasticity of the calf muscles
      interferes with walking after stroke. The aim was to examine this assumption by
      evaluating the contribution of spasticity in the gastrocnemius muscle to walking
      dysfunction in an ambulant stroke population several months after stroke.
      METHODS: Fourteen stroke patients who were able to walk independently and 15
      neurologically normal control subjects were recruited. Both resting and action
      stretch reflexes of the gastrocnemius muscle were investigated under conditions
      that simulated walking. Resting tonic stretch reflexes were measured to assess
      spasticity whereas action tonic stretch reflexes were measured to assess the
      possible contribution of spasticity to gait dysfunction. RESULTS: Two thirds of
      the stroke patients exhibited resting tonic stretch reflexes which indicate
      spasticity, whereas none of the control subjects did. However, the stroke
      patients exhibited action tonic stretch reflexes that were of similar magnitude
      to the control subjects, suggesting that their reflex activity during walking was
      not different from that of control subjects. Furthermore, there was no evidence
      that the action stretch reflex in the stroke patients contributed a higher
      resistance to stretch than the control subjects. CONCLUSIONS: Whereas most of the
      stroke patients exhibited spasticity when measured both clinically and
      physiologically, they did not exhibit an increase in resistance to dorsiflexion
      due to exaggerated action tonic stretch reflexes. It is concluded that it is
      unlikely that spasticity causes problems in walking after stroke in ambulant
      patients. Therefore, it seems inappropriate to routinely reduce or inhibit the
      reflex response to improve functional movement in stroke rehabilitation. Factors
      other than spasticity should be considered when analysing walking after stroke,
      so that appropriate treatment is provided to patients.

PMID- 9598680
TI  - Intracranial aneurysms in three patients with disseminated Lyme borreliosis:
      cause or chance association?
AB  - METHODS: Three patients with Borrelia burgdorferi infection and intracranial
      aneurysms are described. RESULTS: All three patients had neurological symptoms.
      Perivascular and vasculitic lymphocytic inflammation were detected in the brain
      biopsy specimen of one patient. The aneurysm was located in the internal carotid
      arteries in two patients and in the basilar artery in one patient. The aneurysm
      ruptured in two patients. CONCLUSIONS: Cerebral lymphocytic vasculitis and
      intracranial aneurysms may be associated with B burgdorferi infection. It is
      suggested that inflammatory changes caused by B burgdorferi in vessel walls may
      be a pathogenetic mechanism for the formation of aneurysms.

PMID- 9598681
TI  - Protein adsorption to hydrocephalus shunt catheters: CSF protein adsorption.
AB  - OBJECTIVE: To assess the quantity and nature of the proteins that adsorb to
      hydrocephalus shunt catheters after implantation, and to determine whether
      sufficient could accumulate to obstruct the catheter. DESIGN: Elution of proteins
      from 102 explanted shunt catheters, with protein assay and electrophoresis of the
      eluate, and scanning electron microscopy (SEM) of the catheters. RESULTS: The
      amount of protein elutable was extremely low, and significant protein, apart from
      a thin film, was not found on SEM. Qualitative analysis disclosed that most of
      the adsorbed protein was albumin. CONCLUSIONS: Protein deposition on
      hydrocephalus catheters does not occur in sufficient quantities to cause catheter
      obstruction.

PMID- 9598682
TI  - Factors associated with psychotic symptoms in Alzheimer's disease.
AB  - OBJECTIVES: Many clinical and biological factors have been reported to be
      associated with the presence of psychosis in patients with Alzheimer's disease,
      although the associations were variable. The aim of this study was to clarify
      factors associated with the presence of psychosis in patients with Alzheimer's
      disease. METHODS: Psychiatric functioning was studied in 228 patients with
      Alzheimer's disease based on the results of the behavioural pathology in
      Alzheimer's disease rating scale or the neuropsychiatric inventory. The effects
      of sex, education level, age, duration of illness, cognitive function, and
      apolipoprotein E genotype were investigated for dichotomous psychotic status with
      a multiple logistic regression analysis. RESULTS: Of the 228 patients with
      Alzheimer's disease, 118 (51.8%) showed evidence of delusions or hallucinations.
      Of these, 94 had delusions only, three had hallucinations only, and 21 had both.
      Older age, female sex, longer duration of illness, and more severe cognitive
      impairment were the factors independently associated with the presence of
      psychosis. The presence of psychosis was not significantly related to either
      educational level or apolipoprotein E genotype. CONCLUSIONS: Age, sex, and
      severity of illness were independent factors associated with the presence of
      psychosis in patients with Alzheimer's disease. The reason why some patients with
      Alzheimer's disease develop psychosis remains unclear. There may be distinctive
      subtypes of Alzheimer's disease or the presence of individual factors which
      affect the development of psychosis.

PMID- 9598684
TI  - Parkinsonism associated with obstructive hydrocephalus due to idiopathic
      aqueductal stenosis.
AB  - Two cases of parkinsonism after recurrent obstructive hydrocephalus due to
      idiopathic aqueductal stenosis are reported. In both patients an extrapyramidal
      syndrome was noted in the absence of contemporaneous evidence of hydrocephalus or
      shunt failure. One of the patients underwent a shunt operation, but showed no
      clinical improvement. However, both patients improved after the administration of
      dopaminergic therapy. The seven previously reported cases of this syndrome were
      reviewed and it is concluded that the prognosis of the parkinsonism is good,
      usually with total, or near total, resolution. It is recommended that if a
      patient with idiopathic aqueduct stenosis develops hydrocephalus or evidence of
      shunt malfunction in association with acute parkinsonism their shunt should be
      replaced. If there is no evidence of hydrocephalus or shunt malfunction they
      should initially be treated with domaminergic medication.

PMID- 9598683
TI  - Frontal cortical synaptophysin in Lewy body diseases: relation to Alzheimer's
      disease and dementia.
AB  - OBJECTIVES: Dementia in Alzheimer's disease correlates closely with loss of
      neocortical synapses. Similar synaptic loss has been shown in patients whose
      Alzheimer's disease is also associated with neocortical and brain stem Lewy
      bodies. The aim was to determine if dementia in Lewy body disease was associated
      with diminished concentrations of midfrontal cortex synaptophysin. METHODS: An
      immunobinding assay was used to measure synaptophysin in postmortem samples of
      midfrontal cortex from 89 patients with Alzheimer's disease (ages 59-100, mean
      79), 22 with combined Lewy body disease and Alzheimer's disease (ages 69-103,
      mean 79), 15 demented patients with "pure" Lewy body disease (ages 57-80, mean
      74), nine with neocortical and brain stem Lewy bodies who had Parkinson's disease
      but were not demented (ages 68-85, mean 79), and 20 neurologically normal
      controls (ages 58-89, mean 75). The diagnosis was confirmed in all cases by
      detailed neuropathological examination of the contralateral hemibrain. Seven of
      the patients in the pure Lewy body disease with dementia group had initially
      presented with parkinsonism and eight with dementia. RESULTS: Synaptophysin
      concentrations (arbitrary units (AU)/microg) in patients with Alzheimer's disease
      (mean 79 (SD 28)) or combined Lewy body disease and Alzheimer's disease (mean 83
      (SD 33)) were significantly lower than in controls (mean 115 (SD 29)) (p=0.002).
      Synaptophysin concentrations in demented patients with pure Lewy body disease
      (mean 106 SD 39) and patients with Lewy body disease who were not demented (mean
      101 (SD 18)) did not differ significantly from control values or from each other.
      CONCLUSION: Loss of midfrontal cortex synapses probably contributes to dementia
      in Lewy body disease when Alzheimer's disease is also present but not to the
      dementia of pure Lewy body disease.

PMID- 9598685
TI  - Line bisection in hemianopia.
AB  - The effect of hemianopia on line bisection is not known. To study this, manual
      line bisection in 30 patients with unilateral cerebral hemispheric lesions was
      examined. The mean bisection point in a group of eight patients with left
      hemineglect was biased rightward (ipsilaterally), as expected. Among the
      remaining 22 patients, eight had right hemianopic visual defects, eight had left
      hemianopic visual defects, and six had normal visual fields. Both groups of
      patients with contralateral visual field defects had mean bisection points biased
      contralaterally, compared with 68 normal subjects. This bias was less than the
      ipsilateral (opposite) bias of patients with hemineglect. Contralateral bisection
      bias was more evident in those whose field defect involved the macular region. No
      bias was seen in patients with neither field defects nor hemineglect. The
      contralateral bias in hemianopia may represent either non-veridical spatial
      representation within a visual hemifield or a consequence of the strategic
      adaptation of attention into contralateral hemispace after hemianopia.

PMID- 9598687
TI  - Severe neuropathy after high dose carboplatin in three patients receiving
      multidrug chemotherapy.
AB  - Three patients are described who developed a severe neuropathy after chemotherapy
      with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum
      (carboplatin). This toxic side effect, which is unusual at conventional doses,
      might become more frequent as increasing doses are administered to overcome drug
      resistance in cancer treatment, and might limit its use at very high doses before
      haematopoietic stem cell transplantation.

PMID- 9598686
TI  - Common variable immunodeficiency leading to spinal subacute combined degeneration
      monitored by MRI.
AB  - A patient is reported on with a common variable immunodeficiency syndrome (CVID),
      in whom chronic gastritis with antibodies against parietal cells and a
      cytomegalovirus associated enteritis led to vitamin B12 deficiency with
      consecutive subacute combined degeneration of the spinal cord. The resulting
      medullary changes, most probably representing demyelination, were visualised with
      MRI. The effects of treatment were also monitored over three years by MRI and
      clinical examination. The resolution of the MRI changes correlated with clinical
      improvement of the patient's signs. In the medical literature only five cases of
      vitamin B12 related spinal cord changes have been identified by MRI; none was
      caused by a CVID syndrome.

PMID- 9598688
TI  - Transient regression of an intracranial germ cell tumour after intravenous
      steroid administration: a case report.
AB  - Magnetic resonance imaging showed transient regression of the lesion after
      intravenous steroid administration in a patient with intracranial multifocal germ
      cell tumour. Prominent lymphocyte infiltration of the tumour was seen at
      histological examination and presumably accounts for the regression. Germ cell
      tumour must be included in the differential diagnosis of intracranial mass
      lesions sensitive to steroids.

PMID- 9598689
TI  - Post-traumatic stimulus suppressible myoclonus of peripheral origin.
AB  - A patient is described who presented with myoclonus of the first dorsal
      interosseus muscle of the right foot. This myoclonus occurred 18 months after
      trauma of the cutaneous branch of the deep peroneal nerve on the dorsal aspect of
      the foot. Tactile stimulation in the dermatome of this nerve, or an anaesthetic
      block of the deep peroneal nerve stopped the myoclonus. The different innervation
      between the efferent motor activity responsible for the movements and the sensory
      afference suppressing it points firmly towards involvement of central
      connections. However, abolition of the movement by anaesthesia suggests the
      presence of a peripheral ectopic generator. This finding confirms that focal
      myoclonus can have its origin in the peripheral nervous system and may be
      modulated by sensory inputs.

PMID- 9598690
TI  - Acute myelitis with hyperIgEaemia and mite antigen specific IgE: atopic myelitis.
AB  - An occurrence of acute localised myelitis was recently seen in four adult
      patients with atopic dermatitis who had hyperIgEaemia and mite antigen specific
      IgE. The total and mite antigen specific IgE was therefore studied in serum
      samples from 19 consecutive patients with acute localised myelitis of unknown
      aetiology, 56 patients with clinically definite multiple sclerosis, and 40
      healthy controls. The total IgE concentration was significantly higher in acute
      localised myelitis (median=360 U/ml) than in multiple sclerosis (median=52 U/ml,
      p<0.0001) and the controls (median=85 U/ml, p=0.0002). The specific IgE to
      Dermatophagoides pteronyssinus was found more often in patients with acute
      localised myelitis (95%) than in patients with multiple sclerosis (34%, p<0.0001)
      and the controls (35%, p<0.0001) and the specific IgE to Dermatophagoides farinae
      was similar (acute localised myelitis 79%, multiple sclerosis 29% (p<0.0001),
      controls 30%, (p=0.0003). Atopic dermatitis coexisted more commonly in patients
      with acute localised myelitis (37%) than in patients with multiple sclerosis (0%,
      p<0.0001) and the controls (7.5%, p=0.0089). Therefore, acute localised myelitis
      with hyperIgEaemia, in which atopy to mite antigens seems to exist, may be a
      distinct subtype of allergic myelitis-that is, atopic myelitis.

PMID- 9598691
TI  - Early accounts of epilepsy: a synopsis.

PMID- 9598693
TI  - REM sleep behaviour disorder differentiates pure autonomic failure from multiple
      system atrophy with autonomic failure.
AB  - Ten patients with primary autonomic failure, followed up in a prospective
      clinical and laboratory study, were finally diagnosed as pure autonomic failure
      or multiple system atrophy with autonomic failure. Polysomnographic studies were
      performed in all patients. Whereas all four patients with multiple system atrophy
      complained of sleep related episodes suggesting REM sleep behaviour disorder
      (RBD) confirmed by polysomnography, RBD remained absent in the remaining six
      patients with pure autonomic failure. The data indicate that RBD is an important
      clinical feature, often heralding multiple system atrophy, but which is absent
      throughout the course of pure autonomic failure; its recognition can thus be
      useful in the prognostic evaluation of early primary autonomic failure syndromes.

PMID- 9598692
TI  - Hyperammonaemic encephalopathy after initiation of valproate therapy in
      unrecognised ornithine transcarbamylase deficiency.
AB  - Ornithine transcarbamylase deficiency is an X linked disorder and the most common
      inherited cause of hyperammonaemia. Fluctuating concentrations of ammonia,
      glutamine, and other excitotoxic amino acids result in a chronic or episodically
      recurring encephalopathy. A heterozygous female patient first presented with
      protein intolerance, attacks of vomiting, and signs of mental retardation in
      early childhood. At the age of 16 complex partial seizures occurred which were
      treated with sodium valproate. Seven days after initiation of valproate therapy,
      she developed severe hyperammonaemic encephalopathy with deep somnolence. The
      maximum concentration of ammonia was 480 micromol/l. After withdrawal of
      valproate, three cycles of plasma dialysis, and initiation of a specific therapy
      for the inborn metabolic disease, ammonia concentrations fell to normal values.
      The patient remitted, returning to her premorbid state. Valproate can cause high
      concentrations of ammonia in serum in patients with normal urea cycle enzymes and
      may worsen a pre-existing hyperammonaemia caused by an enzymatic defect of the
      urea cycle. Sufficient diagnostic tests for the detection of metabolic disorders
      must be performed before prescribing valproate for patients with a history of
      encephalopathy.

PMID- 9598694
TI  - Intraventricular haemorrhage in pregnancy due to Moya-moya disease.

PMID- 9598695
TI  - Hemifacial spasm.

PMID- 9598696
TI  - Intracranial venous and dural sinus thrombosis due to protein S deficiency in a
      patient with AIDS.

PMID- 9598697
TI  - Serious neurological manifestations of ciguatera: is the delay unusually long?

PMID- 9598699
TI  - Sensory sleep starts.

PMID- 9598698
TI  - Isolated ataxia and autonomic dysfunction: a new variant of Guillain-Barre
      syndrome?

PMID- 9598700
TI  - High concentrations of PS-1 mRNA in skin fibroblasts of patients with Down's
      syndrome.

PMID- 9598701
TI  - Dysgeusia resulting from internal carotid dissection. A limited glossopharyngeal
      nerve palsy.

PMID- 9598702
TI  - Psychiatric symptoms in MELAS; a case report.

PMID- 9598703
TI  - Primary granulomatous hypophysitis not responsive to pulsed high dose
      prednisolone therapy: case report.

PMID- 9598704
TI  - Changes in liver cirrhosis death rates in different countries in relation to per
      capita alcohol consumption and Alcoholics Anonymous membership.
AB  - OBJECTIVE: This study examines how trends in liver cirrhosis relate to per capita
      alcohol consumption and Alcoholics Anonymous (AA) membership in 33 countries
      between 1965 and 1991. It was expected that reductions in liver cirrhosis deaths
      seen in many countries would be related to both decreased consumption and
      increased AA membership. METHOD: Data on liver cirrhosis death rates, alcohol
      consumption and AA membership were gathered from a variety of international
      sources. The data were analyzed with regression analyses (Ordinary Least
      Squares). RESULTS: Cirrhosis deaths and alcohol consumption levels were
      positively related in all analyses. In two of the four analyses, the negative
      relationship between cirrhosis deaths and AA group rates was marginally
      significant. CONCLUSIONS: Liver cirrhosis rates were strongly related to alcohol
      consumption and showed some relationship to AA group rates. The modest impact of
      AA may be due to the weakness of the true relationship but also to incompleteness
      in the cirrhosis and AA data in some countries.

PMID- 9598705
TI  - Alcohol and morbidity in the Lung Health Study.
AB  - OBJECTIVE: There is a well documented J-shaped relationship between alcohol
      consumption and mortality that is not fully understood. Differences between
      studies, particularly in the use of cigarette smoking as a covariate, may
      partially explain inconsistencies in findings. This study sought to clarify the
      nature of this alcohol-smoking-mortality relationship. METHOD: The Lung Health
      Study enrolled 5,887 (3,702 male; 95% white) cigarette smokers with airways
      obstruction, aged 35 to 60. Measures of smoking, drinking and body mass index
      were available annually over the 5-year duration of the study, and pattern of
      alcohol use and diastolic blood pressure were assessed at baseline. Heavy
      drinkers were excluded from the sample. Documented evidence of hospitalizations
      was used in establishing morbidity. Proportional hazards regression was used for
      analysis. RESULTS: A significant protective effect of moderate drinking was found
      among men, but not women. There was also no apparent interaction between smoking
      status and drinks per week (both time dependent) in these data on morbidity and
      mortality. A baseline pattern of drinking eight or more drinks per occasion, but
      less than once a month, among men was associated with fewer hospitalizations and
      deaths. CONCLUSIONS: This study confirmed the general relationships between use
      of alcohol and illness or death, but with a few unexpected results. Further
      investigation is needed to identify whether these unexpected findings were due to
      our somewhat unique sample, to our use of hospitalization as the primary outcome
      measure, or to other causes.

PMID- 9598706
TI  - Alcohol activates the cerebral reward system in man.
AB  - OBJECTIVE: We investigated the effect of 0.07% alcohol on regional brain activity
      at rest and during cognitive performance in order to elucidate the anatomical
      substrate for the effects of alcohol in man as well as to clarify the interaction
      between changes in cerebral activity induced by cognitive performance and alcohol
      inebriation. METHOD: Regional cerebral blood flow (3D-PET, 15O Butanol) was
      measured in 13 male, nonalcoholic volunteers. Each subject was scanned 12 times,
      three scans in each of the following four situations: sober/rest, sober/test and
      inebriated/rest, inebriated/test. We used statistical parametric mapping and a
      computerized brain atlas for localization. RESULTS: Alcohol induced a sense of
      inebriation and elation as well as a relative increase of the cerebral blood flow
      in medial parts of the temporal lobes, in the anterobasal parts of the anterior
      cingulate cortex including the septal region. In addition, there was an increase
      of blood flow in midline parts of the lower brain stem. Relative decreases of
      flow were observed in the cerebellum and in the occipital cortex bilaterally. In
      the sober state, a computerized perceptual maze test and a (silent) serial seven
      test induced two distinct neocortical activation patterns that were specific to
      the tasks. Alcohol did not change these patterns and the test performance was
      also uninfluenced. CONCLUSIONS: A moderate dose of alcohol selectively activates
      target structures that pertain to the so-called cerebral reward system and the
      ascending reticular activating system. Alcohol (approximately 0.07%) appears to
      have only minor effects in the neocortical systems that are involved in on-line
      cognitive activity. This apparent independence between the subcortical alcohol
      target and the neocortical cognitive mechanisms is a new finding that appears to
      be of importance for an understanding of the effect of moderate doses of alcohol
      on the brain.

PMID- 9598707
TI  - Evaluation of a four- versus six-week length of stay in the Navy's alcohol
      treatment program.
AB  - OBJECTIVE: Attempts to balance escalating health care costs with resource
      downsizing have prompted alcohol treatment directors in the U.S. Navy to consider
      reducing the standard length of stay in treatment. The objectives of this study
      were to (1) determine whether a 4-week inpatient treatment program is as
      effective as a 6-week program, and (2) explore the potential for matching
      patients to a 4- or 6-week program according to the severity of their condition
      at intake. METHOD: A total of 2,823 active-duty alcohol-dependent inpatients
      (2,685 men, 138 women) at 12 Navy treatment facilities participated in the
      evaluation. All facilities conducted a 6-week program until data had been
      collected for 1,380 participants; they then switched to a 4-week program (n =
      1,443). Background information and clinical profile were obtained when patients
      entered treatment; 1-year outcome data (e.g., alcohol use, behavior problems, job
      performance, quality of life) were obtained from participants, work supervisors
      and aftercare advisors. Hierarchical multiple regression analyses were used to
      assess the effect of length of stay on outcome and to examine patient-program
      interactions. RESULTS: The single best predictor of success at 1 year was months
      of aftercare attendance. Program membership failed to explain any of the observed
      differences in the criterion measures, once the effects of other predictors had
      been taken into account. Severity of condition and patient-program interactions
      were likewise nonsignificant. CONCLUSIONS: It was concluded that a reduction in
      length of stay from 6 weeks to 4 weeks in the Navy's inpatient alcohol treatment
      program would not have an adverse effect on outcome.

PMID- 9598708
TI  - Mode effects on self-reported alcohol use and problem drinking: mail
      questionnaires and personal interviewing compared.
AB  - OBJECTIVE: Much attention is paid to the influence of different data collection
      methods on the quality of self-reported drinking behavior estimates. Thus far,
      however, the findings show inconsistencies. Therefore, a comprehensive study was
      conducted to compare data on alcohol use and alcohol-related problems obtained by
      mail survey and personal interviews. METHOD: A general population survey on
      alcohol was conducted among a random sample of 8,000 Dutch inhabitants of
      Rotterdam aged 16 to 69. A small sample (n = 500) of the total sample (N = 8,000)
      was personally interviewed and the others (n = 7,500) received a mailed
      questionnaire. The response rate was 44% (N = 3,537). Respondents of the mail
      survey and personal interviews are compared on overall response rate, item
      nonresponse rate, background factors, self-reported alcohol use, alcohol-related
      problems and problem drinking. RESULTS: No notable differences in self-reported
      alcohol use, alcohol-related problems or problem drinking were found by data
      collection mode. This holds for both the total general population and for men and
      women separately. The overall response rate was somewhat higher for the personal
      interviews. No important significant differences were found in item nonresponse
      or background factors. CONCLUSIONS: The absence of notable differences in
      estimated self-reported drinking behavior by mail survey and personal interviews
      indicates that both data collection methods yield comparable results. This is
      true for both the total population and for men and women separately.

PMID- 9598709
TI  - Comparison of treatment utilization and outcome for Hispanics and non-Hispanic
      whites.
AB  - OBJECTIVE: To examine the use of formal alcohol treatment and Alcoholics
      Anonymous (AA) by Hispanics and non-Hispanic whites, and to compare ethnic groups
      on posttreatment functioning. METHOD: Data from a publicly funded substance abuse
      treatment center in New Mexico were used to investigate possible differences
      between Hispanic (n = 46) and non-Hispanic white (n = 62) men (n = 76) and women
      (n = 32) on percent days alcohol therapy and AA attendance for 6 months after
      study recruitment. RESULTS: Hispanic clients were more often male (80% vs 63%),
      had fewer years of education (mean = 11.6 vs 12.6) and were less likely to live
      alone (7% vs 29%) than were non-Hispanic white clients. The heavy drinking
      (drinks per drinking day mean = 16.7; standard drink units in prior 90 days mean
      = 941.00) and few abstinent days (mean = 0.44) that characterized both groups at
      intake improved over time with Hispanics engaging in more formal alcohol therapy
      sessions but attending fewer AA meetings than non-Hispanic whites over the course
      of 6 months of follow-up. Attendance at treatment and AA were separately
      associated with decreased intensity and quantity of alcohol use, but not
      abstinent days, for both ethnic groups. CONCLUSIONS: Hispanic and non-Hispanic
      white clients used somewhat different treatment strategies to deal with alcohol
      related problems, these paths, however, ultimately resulted in similar
      posttreatment drinking outcomes (frequency, intensity and quantity of alcohol
      consumption).

PMID- 9598710
TI  - The impact of maternal drinking during and after pregnancy on the drinking of
      adolescent offspring.
AB  - OBJECTIVE: The impact of prenatal maternal drinking on alcohol consumption in
      adolescent offspring was examined among boys and girls separately. METHOD: A
      prospective longitudinal sample of 185 mother-firstborn child dyads was used to
      examine the impact of maternal self-reported alcohol consumption during pregnancy
      on adolescent self-reported lifetime and current drinking, controlling for
      potential confounding factors. RESULTS: In this representative general population
      sample, maternal drinking during pregnancy, particularly continuous moderate to
      heavy consumption, had a significant positive effect on adolescent daughters'
      current drinking, but a slight negative effect on sons' lifetime drinking. The
      sex-specific prenatal effect on current drinking persisted with controls for
      prenatal maternal cigarette smoking, current maternal drinking, child-rearing
      practices (i.e., maternal-child closeness, monitoring and a rule against
      drinking) and the adolescent's problem behaviors in childhood. Prenatal maternal
      smoking was also associated with elevated rates of adolescent drinking,
      particularly current drinking. Of the child-rearing variables, only a rule
      against drinking decreased adolescent drinking. CONCLUSIONS: Selected prenatal
      factors may constitute risks for alcohol consumption among adolescent daughters.
      The results are discussed in light of animal models that document increased
      vulnerability among female offspring to the deleterious effects of gestational
      alcohol exposure. Implications for understanding the risk factors associated with
      adolescent alcohol use are discussed.

PMID- 9598711
TI  - Alcohol portrayal on prime-time television: manifest and latent messages.
AB  - OBJECTIVE: The research in this article is designed to improve our understanding
      of alcohol messages embedded in prime-time television, especially when adolescent
      characters are shown portraying or consuming alcohol. METHOD: Manifest and latent
      content analyses are used to assess the frequency of alcohol portrayal in prime
      time television and the personality traits (powerful, admirable, smart) of
      characters shown consuming or portraying alcohol on prime-time television. The
      sample includes 224 hours of programming across 276 programs on four major
      networks. RESULTS: Alcoholic beverages were the most frequently portrayed food or
      drink. The prominence of alcohol in prime-time television applies to all
      characters, including adolescents. The proportion of all food and drink incidents
      accounted for by alcohol equaled .14 for male and .20 for female adolescent
      television characters. Moreover, when adolescent characters are involved with
      alcohol incidents, they are more likely to be shown consuming this alcohol than
      are adults. A significant finding was that adolescents portraying alcohol in
      programming were shown to have significantly more negative personality
      characteristics than did characters in older age groups. CONCLUSIONS: Compared
      with other studies, this study finds higher rates of alcohol portrayal by
      adolescents on prime-time television. The negative character portrayal of
      adolescents involved with alcohol is encouraging. However, adult and high-income
      characters involved with alcohol, who might serve as role models for younger
      adults are, on average, shown with positive personality characteristics.

PMID- 9598712
TI  - Parental and peer influences on the onset of heavier drinking among adolescents.
AB  - OBJECTIVE: Less is known about heavier drinking in adolescents than about alcohol
      initiation. The present study examined the emergence of regular (weekly) and
      heavy episodic (five or more drinks at a time) adolescent drinking as a function
      of social influence (modeling and social control) from parents and peers. METHOD:
      A three-wave study was conducted using a representative household sample of
      families in metropolitan Buffalo, New York (N = 612). Over half (54%) of the
      adolescent respondents were female. Black families made up 30% of the sample.
      Interviews were conducted at 1-year intervals. Adolescent drinking was
      dichotomized at each wave into abstinence/light drinking versus regular drinking.
      Logistic regression including only adolescents who were abstainers/light drinkers
      at Wave 1 was performed to assess which Wave- variables could predict regular
      drinking onset by Wave 2; a similar analysis examined the onset of heavy episodic
      drinking by Wave 2. Parallel analyses using Wave-2 variables to predict the onset
      of the drinking outcomes by Wave 3 were also conducted. RESULTS: Across the
      different analyses, the strongest psychosocial predictors of advancement to
      heavier drinking were friend's drinking and low parental monitoring. Also, white
      adolescents were at greater risk than their black counterparts. CONCLUSIONS: A
      multidimensional approach to prevention that addresses different processes of
      influence (e.g., modeling and social control) involving both parental and peer
      domains is likely to be most successful in deterring the onset of heavier
      drinking in adolescents.

PMID- 9598713
TI  - The association of educational achievement and school dropout with risk of
      alcoholism: a twenty-five-year prospective study of inner-city children.
AB  - OBJECTIVE: This prospective study is focused on the characteristics leading to
      alcohol use disorders in early adulthood among a cohort of black children. The
      principal aim of this work is to examine the impact of educational attainment,
      school dropout and early school adaptation on the development of alcohol abuse
      and dependence in adulthood. METHOD: From a population that consisted of 1,242
      first graders in 1966-67, a total of 953 were interviewed at age 32-33 about
      their current alcohol and drug use, educational attainment, employment and family
      situation. RESULTS: Diagnoses of alcohol abuse and dependence were defined
      according to DSM-III-R criteria resulting in identification of 13.5% as having a
      lifetime alcohol use disorder. Early predictions of an alcohol use disorder in
      adulthood included early reports of underachievement in first grade by the
      child's teacher, dropping out of high school, whether the family set definite
      rules about school during adolescence, and how often the adolescent worked on
      homework with his/her family. CONCLUSIONS: The results suggest that educational
      achievement and some early adaptive behaviors in school are associated with risk
      for alcohol use disorders. The public health importance of the findings are
      discussed.

PMID- 9598714
TI  - Effectiveness of cognitive-behavioral therapy for smokers with histories of
      alcohol dependence and depression.
AB  - OBJECTIVE: Alcohol dependence and major depression have been associated with
      heavy cigarette use and poor smoking-treatment outcomes. This preliminary study
      examined the efficacy of a mood management intervention for smoking cessation in
      abstinent alcoholics with a history of major depression. METHOD: Participants
      were 29 (15 female, 14 male) heavy smokers (mean cigs/day = 30.2), with an
      average of 6.8 years of continuous abstinence from alcohol and drugs, randomized
      to behavioral counseling (BC) (n = 16) or behavioral counseling + cognitive
      behavioral mood management (CBT) (n = 13). A 2 x 5 repeated measures design was
      used to evaluate the effectiveness of the interventions on smoking outcome at
      baseline, posttreatment and at 1-, 3- and 12-month-follow-up. Self-reported
      smoking status was verified with biochemical (COa) and informant report. RESULTS:
      Verified self-report indicated that significantly more smokers in CBT quit by
      posttreatment (69.2%; 9 of 13) than in BC (31.3%; 5 of 16) (chi2 = 4.14, 1 df, p
      = .04). These abstinence rates remained unchanged at 1-month follow-up. At 3
      month follow-up, differences in smoking abstinence rates were nonsignificant
      between CBT (46.2%; 6 of 13) and BC (25.0%; 4 of 16) conditions. However, at 12
      month follow-up, significantly more participants in CBT were abstinent from
      smoking (46.2%; 6 of 13) than in BC (12.5%; 2 of 16) (chi2 = 4.07, 1 df, p =
      .04). CONCLUSIONS: The results suggest that interventions focused on managing
      negative mood may benefit these high-risk, comorbid smokers.

PMID- 9598715
TI  - Child sexual and physical abuse and alcoholism: a review.
AB  - OBJECTIVE: To examine possible relations between child sexual or physical abuse
      and adult alcoholism. METHOD: Studies reviewed included prospective studies,
      retrospective studies on the prevalence of child sexual or physical abuse in
      alcoholics and nonalcoholics, and retrospective studies in mental health clients
      and in population samples comparing the prevalence of alcohol use disorders in
      abused and nonabused subjects. RESULTS: Prospective studies do not indicate a
      significant association between child sexual or physical abuse and alcoholism. In
      contrast, studies among alcoholic women do suggest a relationship. Also, a
      significantly higher prevalence of alcohol problems in abused women than in
      nonabused women is found in population samples. The results of studies among
      mental health clients are inconclusive. In addition, several methodological
      limitations should be taken into consideration when evaluating results of the
      available studies. CONCLUSIONS: Current evidence is insufficient to draw
      conclusions about relationships between child sexual or physical abuse and
      alcoholism among men. Among females, however, there is a higher likelihood of
      alcohol problems if they were sexually or physically abused as children.

PMID- 9598716
TI  - A simple and efficient method for microdissection and microFISH.
AB  - A simple and efficient method for the dissection of (marker) chromosomes,
      (micro)nuclei, and chromosome regions is presented. Before microdissection,
      metaphases are overlaid with milli-Q water to rehydrate the chromosomes, which
      makes them soft and sticky. The dissected chromosome fragments are dissolved
      without proteinase-K or topoisomerase treatment and directly amplified using a
      degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR). The
      advantages of this microFISH method over previously reported methods are: (1)
      microdissection in this way is very fast; (2) a chromosome, marker,
      (micro)nucleus, or chromosome region is collected as a whole using only one
      microneedle; (3) the dissected material sticks tightly to the needle without the
      risk of getting lost; (4) no Sequenase is used in the DOP-PCR reaction which
      reduces the risk of contamination.

PMID- 9598717
TI  - Localisation of the gene for glycogen storage disease type 1c by homozygosity
      mapping to 11q.
AB  - The microsomal glucose-6-phosphatase (G6Pase) complex regulates the final step in
      glucose production from glycogenolysis and gluconeogenesis. Glycogen storage
      disease type 1c (GSD-1c) results from deficient activity of the phosphate/
      pyrophosphate transporter of this complex and is associated with neutropenia as
      well as hepatomegaly and hypoglycaemia. Using three affected subjects from a
      single highly consanguineous family, we have used homozygosity mapping to
      localise the gene responsible for GSD-1c to a 10.2 cM region on 11q23.3-24.2. The
      maximum lod score was 3.12. GSD-1c is therefore distinct from GSD-1a, which has
      been shown previously to be caused by mutations in the G6Pase gene on chromosome
      17.

PMID- 9598719
TI  - Molecular studies in Finnish patients with familial juvenile nephronophthisis
      exclude a founder effect and support a common mutation causing mechanism.
AB  - Familial juvenile nephronophthisis (NPH) is an autosomal recessive
      tubulointerstitial kidney disease associated with formation of medullary and
      corticomedullary cysts. It progresses to end stage renal failure and its
      biochemical defect is unknown. An NPH locus has been assigned to a 2 cM interval
      on chromosome 2q13 by linkage studies. Homozygous deletions of approximately 250
      kb have been detected in 80% of familial cases and 65% of sporadic cases and a
      common mutation mechanism has been suggested. We examined 14 Finnish families for
      the presence or absence of a deletion. After detecting a deletion in 12 patients
      belonging to nine families, we studied a possible founder effect by haplotype
      analysis using markers D2S340, D2S1889, and D2S1893. No common ancestral disease
      associated haplotype was found suggesting no founder effect. Results of pairwise
      linkage analyses were suggestive of linkage in the nine families with a deletion
      (lod scores of 1.39-3.89 at a recombination fraction of 0). Negative lod scores
      were obtained in the five families without a deletion suggesting that the disease
      locus in these families lies elsewhere. The end stage renal disease occurred at a
      more advanced age in patients without a deletion compared to patients with a
      deletion, indicating a phenotypic difference between these two groups.

PMID- 9598720
TI  - Genetic localisation of mental retardation with spastic diplegia to the
      pericentromeric region of the X chromosome: X inactivation in female carriers.
AB  - We report on two brothers and one maternal cousin with severe mental retardation,
      microcephaly, short stature, cryptorchidism, and spastic diplegia. The patients
      were born to normal and non-consanguineous parents. All other members of the
      family, almost exclusively females, were clinically normal, suggesting X linked
      inheritance. By multipoint linkage analysis with markers spanning the whole X
      chromosome, we have tentatively assigned the underlying genetic defect to Xp11.4
      q21, achieving a maximum lod score of 1.3. This localisation overlaps MRXS3, a
      syndromic form of mental retardation resembling that found in the family
      described here, although with a milder presentation. We discuss the possibility
      that both phenotypes might be allelic variants of the same gene localised in the
      pericentromeric region of the X chromosome. Analysis of the X inactivation
      pattern in one potential and three obligate carrier females showed non-random
      inactivation of the allele linked to the disease. This finding may be interpreted
      as: (1) a negative selection effect on cells bearing the mutation on the active X
      chromosome; (2) both the disease causing gene and the X inactivation centre are
      simultaneously affected by the same alteration, a deletion for instance; or (3)
      the skewed inactivation is the consequence of an independent event randomly
      associated with the disease. In any case, the observation of consistent X
      inactivation supports X linkage of the disease.

PMID- 9598718
TI  - Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: a
      new X linked contiguous gene deletion syndrome?
AB  - We describe a family with four members, a mother, two sons, and a daughter, who
      show clinical features consistent with X linked Alport syndrome. The two males
      presented with additional features including mental retardation, dysmorphic
      facies with marked midface hypoplasia, and elliptocytosis. The elliptocytosis was
      not associated with any detectable abnormalities in red cell membrane proteins;
      red cell membrane stability and rigidity was normal on ektacytometry. Molecular
      characterisation suggests a submicroscopic X chromosome deletion encompassing the
      entire COL4A5 gene. We propose that the additional abnormalities found in the
      affected males of this family are attributable to deletion or disruption of X
      linked recessive genes adjacent to the COL4A5 gene and that this constellation of
      findings may represent a new X linked contiguous gene deletion syndrome.

PMID- 9598721
TI  - Organisation of the human PAX4 gene and its exclusion as a candidate for the
      Wolcott-Rallison syndrome.
AB  - Neonatal diabetes mellitus is a rare condition, the causes of which are mostly
      unknown. One well defined though very rare entity is the autosomal recessive
      Wolcott-Rallison syndrome, in which permanent neonatal diabetes, osteopenia, and
      epiphyseal dysplasia occur. Only five previous families have been reported, and
      here we describe the second in which parental consanguinity was present. The
      proband was born to first cousin parents and died at 2 years from the sequelae of
      poorly controlled diabetes. To test the hypothesis that mutation of PAX4,
      required in the mouse for pancreatic islet beta cell development, might cause
      WRS, the structure of the human PAX4 gene was deduced and DNA from two unrelated
      WRS patients sequenced. No PAX4 mutation was present, though the entire coding
      region was sequenced in both patients. It therefore appears unlikely that PAX4 is
      involved in the aetiology of Wolcott-Rallison syndrome, though it remains a good
      candidate for other forms of neonatal diabetes mellitus.

PMID- 9598722
TI  - Myotonia congenita in northern Finland: an epidemiological and genetic study.
AB  - An epidemiological and genetic investigation of myotonia congenita was carried
      out in northern Finland. Altogether 58 patients were identified (of whom 54 lived
      in the study area) in 23 families, with a prevalence of 7.3 per 100000. The
      majority of the families originated from a sparsely populated area in western
      Lapland. The mean age at onset of the disease was 11 years with a range of 2 to
      45 years. The mean time that had passed before verification of the clinical
      disease was 18 (SD 14) years. The sex ratio M/F was 2.2/1.0. Forty-seven cases
      were familial and 11 were sporadic. In six families/pedigrees the inheritance was
      compatible with autosomal recessive and in two families with autosomal dominant
      inheritance. In five additional families, in which autosomal recessive
      inheritance seemed most plausible, vertical transmission was also noticed. This
      could be explained either by consanguinity of the parents or by variant
      expression of the mutation(s) involved. Our results suggest that myotonia
      congenita is unusually frequent in northern Finland, most probably as a
      consequence of an enrichment of the gene mutation(s) in the population.

PMID- 9598723
TI  - Chromosome mapping of Rett syndrome: a likely candidate region on the telomere of
      Xq.
AB  - Rett syndrome (RS) is a disease of neurological development. First reported 30
      years ago in 1966, its biological and genetic basis remains obscure. RS is
      commonly thought of as an X linked dominant disorder lethal to hemizygous males.
      The few familial cases would arise through mosaicism or because of occasional
      females failing to manifest the disorder through skewed X inactivation in
      relevant cell types. We have one family where the mother and daughter are
      affected with RS, and which can be explained according to this hypothesis. If the
      alternative proposal of Thomas (1996) is correct, that the lack of males affected
      by such disorders is the result of a high male to female ratio of germline
      mutations rather than of gestational lethality, then the RS gene should be
      located on the grandpaternal chromosome. Genomic screening with markers covering
      the whole X chromosome has been performed. Studies using multiple informative
      markers indicate that the RS locus is likely to be located close to one of the X
      chromosome telomeres. Further investigations in eight additional families suggest
      the most likely region for the RS gene to be is the distal part of Xq (Xq28).

PMID- 9598724
TI  - Population genetics of hyperphenylalaninaemia resulting from phenylalanine
      hydroxylase deficiency in Portugal.
AB  - In order to elucidate the molecular basis of phenylketonuria (PKU) in Portugal, a
      detailed study of the Portuguese mutant phenylalanine hydroxylase (PAH) genes was
      performed. A total of 222 mutant alleles from 111 PKU families were analysed for
      26 mutations and restriction fragment length polymorphismlvariable number tandem
      repeat (RFLP/VNTR) haplotypes. It was possible to characterise 55% of the mutant
      alleles, in which 14 different mutations (R261Q, V388M, IVS10nt-11, I65T, P281L,
      R252W, R158Q, L348V, Y414C, L311P, Y198fsdel22bp, R408W, R270K, and R261X) and
      three polymorphisms (Q232Q, V245V, and L385L) were identified. A total of 14
      different haplotypes were observed, with a high prevalence of haplotype 1 among
      mutant and normal alleles. The results reported in this study show considerable
      genetic heterogeneity in the Portuguese PKU population, as has also been
      described for other southern European populations.

PMID- 9598726
TI  - Contracting for clinical genetic services: the Welsh model.
AB  - In a time of increasing competition for clinical services resources, it is
      imperative that health professionals actively participate in the commissioning
      process in order to ensure that established clinical standards are not
      compromised. Introduction of the NHS reforms in the UK in the early 1990s
      highlighted the difficulties in contracting for a specialised service such as
      clinical genetics, especially in the absence of a consensus regarding the
      contract currency. An average block contract price for each new family referred
      was introduced in Wales in 1992, and data from the subsequent five years show
      that this charging system is economically feasible and has the advantages of (1)
      recognising the contribution to care of non-medical personnel on the genetics
      team, (2) covering follow up including the counselling of relatives, (3)
      protecting the service from loss of income owing to non-attendance, and (4)
      providing a basis for negotiation when new services are being proposed to
      purchasers. Activity data show that while the majority of conditions incur below
      average cost, the mean cost is influenced by a small number of autosomal dominant
      and X linked disorders. The cost risk to the provider for seeing families over an
      extended period is minimal, as the data establish that family files experience an
      exponential decrease in activation probability over the early years, but this
      becomes constant later on. The robustness of the system is dependent on accurate
      baseline data on referral patterns to the service, recording of activity, and
      staff costs.

PMID- 9598725
TI  - Evidence for anticipation in autosomal dominant limb-girdle muscular dystrophy.
AB  - Anticipation, an increase in severity or decrease in age of onset (AO) inherent
      in the transmission of the disease gene from affected parent to affected child,
      has been increasingly described in human disease. To assess anticipation in a
      large kindred in which autosomal dominant limb-girdle muscular dystrophy (LGMD1A)
      is segregating, age of disease onset was collected from patient interviews of
      affected family members. A total of 25 parent-offspring pairs, in which the
      parents are three (3R), four (4R), or five (5R) generations removed from a common
      founding ancestor, were available for analysis. Life table analyses showed
      significant decreases in age at first reported symptoms in the offspring of the
      3R (chi2=5.55, p=0.02) and 4R (chi2=7.81, p=0.005) parents. Pairwise analyses
      confirmed this decrease with a median decrease of 13 years in transmission to
      offspring from 3R parents and 18 years in transmission to offspring from 4R
      parents. The finding of anticipation in this pedigree suggests that the mutation
      in LGMD1A may be the result of the expansion of an unstable trinucleotide repeat.

PMID- 9598727
TI  - The dystonias.

PMID- 9598728
TI  - Trisomy 2q11.2-->q21.1 resulting from an unbalanced insertion in two generations.
AB  - In this communication, we describe two cases of proximal 2q trisomy (2q11.2-->
      q21.1) resulting from an interchromosomal insertion. The chromosomal origin of
      the insertion was confirmed by fluorescence in situ hybridisation. An unbalanced
      karyotype, 46,XX,der(8) ,ins(8;2) (p21.3; q21.1q11.2), was found in the proband
      and her mother, who both have mild mental retardation, short stature, dysmorphic
      features, insulin dependent diabetes mellitus, and a psychotic illness. This
      family is a rare example of direct transmission of a partial autosomal trisomy.

PMID- 9598729
TI  - Familial neurofibromatosis type 1 associated with an overgrowth syndrome
      resembling Weaver syndrome.
AB  - The simultaneous occurrence of familial neurofibromatosis type 1 (NF1) and an
      overgrowth syndrome resembling Weaver syndrome was observed in two related cases
      (a mother and her son). NF1 was confirmed by molecular genetic analysis showing a
      large deletion at 17q11.2, encompassing the entire NF1 gene. The other symptoms
      in the two cases were similar to the features reported in Weaver syndrome.
      Although the combination of NF1 and an overgrowth syndrome resembling Weaver
      syndrome in this family may be fortuitous, we favour the hypothesis that the
      deletion of the entire gene has caused this combined phenotype. Possible
      pathogenetic mechanisms are discussed. The observation suggests a relation
      between NF1 with an extraordinarily large gene deletion and a Weaver(-like)
      syndrome. This warrants investigation for deletions in the 17q11.2 region in
      Weaver(-like) syndrome patients.

PMID- 9598730
TI  - Simultaneous adrenocortical carcinoma and ganglioneuroblastoma in a child with
      Turner syndrome and germline p53 mutation.
AB  - The predisposition to malignancy that is dominantly inherited in Li-Fraumeni
      syndrome is associated with germline mutations of the tumour suppressor gene p53.
      Although second malignant neoplasms have been described in children with p53
      mutations, the synchronous occurrence of two embryologically different tumours in
      these children has not been reported. A 20 month old girl with failure to thrive
      and congenital heart defects was found to have unilateral adrenal masses which,
      at surgical removal, proved to be an adrenocortical carcinoma and a
      ganglioneuroblastoma. Further investigation showed a germline p53 mutation and
      Turner syndrome. It remains to be determined what effect the 45,X chromosomal
      complement may have on the expression of neoplasms seen in patients with p53
      germline mutations.

PMID- 9598731
TI  - Two adult females with a distinct familial mental retardation syndrome: non
      progressive neurological symptoms with ataxia and hypotonia, similar facial
      appearance, hypergonadotrophic hypogonadism, and retinal dystrophy.
AB  - We describe a familial mental retardation syndrome in a 30 year old, moderately
      mentally retarded female and her 59 year old maternal aunt. Both presented the
      distinct association of (1) a non-progressive neurological syndrome with ataxia
      and hypotonia, (2) similar craniofacial appearance with a narrow forehead,
      prominent supraorbital ridges and tendency to synophrys, deeply set eyes with
      short, upward slanting palpebral fissures, short philtrum, and large mouth, (3)
      hypergonadotrophic hypogonadism, and (4) retinal dystrophy with onset in early
      adulthood.

PMID- 9598732
TI  - Keratosis follicularis spinulosa decalvans: confirmation of linkage to Xp22.13
      p22.2.
AB  - Keratosis follicularis spinulosa decalvans (KFSD) is a rare, X linked disorder
      with skin and eye involvement (MIM 308800). We have studied a large British
      family with KFSD using polymorphic markers from Xp21-p23 and obtained a lod score
      of 2.056 at theta=0 with markers proximal and distal to the KFSD candidate region
      Xp22.13-p22.2 identified by Oosterwijk et al. Our data confirm the linkage to
      Xp22.13-p22.2 observed in the previously reported Dutch family, but fail to
      narrow the candidate interval for the KFSD locus.

PMID- 9598733
TI  - Absence of PAX2 gene mutations in patients with primary familial vesicoureteric
      reflux.
AB  - Vesicoureteric reflux (VUR) is a common childhood condition characterised by
      regurgitation of urine from the bladder to the kidney. It is the commonest cause
      of end stage renal failure in children and an important cause in adults. Primary
      VUR is often familial, suggesting that genetic factors play an important role in
      its aetiology. Recently, VUR was observed as part of a syndrome, involving optic
      nerve colobomas and renal anomalies, caused by mutations of the PAX2 gene. PAX2
      is a member of the paired box family of genes and is expressed in the ureteric
      bud and differentiating nephrogenic mesenchyme of the developing kidney. PAX2 has
      been shown to play a critical role in the development of both the kidney and the
      ureter. The occurrence of VUR in one family with the PAX2 mutation, and the
      expression pattern of PAX2 in developing ureteric bud, strongly suggested that
      PAX2 could be the cause of primary familial VUR. Single strand conformational
      polymorphism (SSCP) analysis of 23 affected subjects in eight families with
      primary familial VUR showed no alterations in exons 2-5 of the PAX2 gene. In
      addition, a polymorphic dinucleotide repeat marker located within the PAX2 gene
      segregated independently of the disease trait in one large family who primarily
      had VUR or reflux nephropathy. These results suggest that PAX2 is not a major
      cause of primary familial reflux.

PMID- 9598734
TI  - Severe testotoxicosis phenotype associated with Asp578-->Tyr mutation of the
      lutrophin/choriogonadotrophin receptor gene.
AB  - Testotoxicosis is a form of male precocious puberty caused by heterogeneous
      activating mutations in the gene for the lutrophin/choriogonadotrophin receptor
      (LHR). A patient with an unusually early and severe presentation of
      testotoxicosis, including profound Leydig cell hyperplasia, was found to have a
      sporadic mutation encoding Asp578-->Tyr. The severe testotoxicosis phenotype
      appears to be related to the strongly activating nature of the Tyr substitution.

PMID- 9598735
TI  - Oral-facial-digital syndrome type IX in a patient with Dandy-Walker malformation.
AB  - We report a girl with oral, facial, and digital anomalies including multiple
      alveolar frenula, lobulated tongue with nodules, a posterior cleft palate,
      hypertelorism, a prominent forehead with a large anterior fontanelle, and
      postaxial polydactyly in both hands and the right foot, features compatible with
      the oral-facial-digital syndrome (OFDS). In addition, she had bilateral
      microphthalmia, optic disc coloboma, and retinal degeneration with partial
      detachment, thus establishing a diagnosis of OFDS type IX. Dandy-Walker
      malformation and retrobulbar cysts were observed on MRI. These additional
      malformations have not been reported in OFDS type IX. The frequent apnoeic spells
      which occurred immediately after birth were relieved after cystoperitoneal shunt
      implantation for hydrocephalus. Considering our case and previous reports of OFDS
      type IX, including two male sibs, a boy born to consanguineous parents, and three
      females, inheritance is probably autosomal recessive.

PMID- 9598736
TI  - Craniosynostosis and chromosome 22q11 deletion.

PMID- 9598737
TI  - Spectrum of clinical features associated with interstitial chromosome 22q11
      deletions.

PMID- 9598738
TI  - Clinical features of chromosome 22q11 deletion.

PMID- 9598739
TI  - Absence of a del(22q11) in a patient with the 3C (craniocerebellocardiac)
      syndrome.

PMID- 9598740
TI  - A mother with VCFS and unilateral dysplastic kidney and her fetus with
      multicystic dysplastic kidneys: additional evidence to support the association of
      renal malformations and VCFS.

PMID- 9598742
TI  - Robinow syndrome.

PMID- 9598741
TI  - New overgrowth syndrome and FGFR3 dosage effect.

PMID- 9598743
TI  - Contact tracing for chlamydia: data on effectiveness.

PMID- 9598744
TI  - How are men with urethral discharge managed in general practice?
AB  - Chlamydia and gonorrhoea remain major causes of morbidity despite the
      availability of effective therapy. Because of the asymptomatic nature of many
      infections, particularly in women, active case finding is necessary to trace and
      offer screening and treatment to sexual contacts of those infected. Genitourinary
      medicine (GUM) clinics provide investigation and treatment for a variety of
      sexual health problems but the proportion of infections treated outside these
      clinics is unknown. A questionnaire survey of general practitioners (GPs) was
      used to examine the prevalence and management of male urethritis in Scotland.
      Responses were received from 277/347 (80%) of GPs. A median of one case/year of
      male urethritis was seen and screening for gonorrhoea and chlamydia was
      undertaken in 82% and 63% of cases not referred to a GUM clinic respectively. Six
      per cent of GPs attempted to trace sexual contacts. Twenty-nine per cent (60) of
      patients were not referred to a GUM clinic and increasing distance to the clinic
      was associated with non-referral. Eleven per cent (18) of patients objected to
      referral to a GUM clinic. There is scope to improve the management of male
      urethritis by providing greater support for GPs, encouraging clinic referral
      where possible and appropriate investigations and treatment when not.

PMID- 9598745
TI  - A new recombinant antigen latex agglutination test (Syphilis Fast) for the rapid
      serological diagnosis of syphilis.
AB  - We report an assessment of Syphilis Fast, a new latex test that uses a pool of 3
      recombinant Treponema pallidum antigens (TpN15, TpN17, and TpN47) for the
      serodiagnosis of syphilis. Specificity was evaluated by screening 1518 unselected
      blood specimens in parallel with Syphilis Fast, the Captia SelectSyph-G EIA and
      the Venereal Disease Research Laboratory (VDRL) cardiolipin antigen test while
      sensitivity was tested using a panel of 99 treponemal sera (treated and
      untreated) representing various stages of infection and 15 treponemal sera
      detected on screening. The specificity of Syphilis Fast on initial testing
      (99.8%) was significantly higher (P<0.02) than that of Captia SelectSyph-G
      (99.2%) and the VDRL (99.1%): the specificity of Syphilis Fast remained
      significantly higher (P<0.02) after repeat testing (respective values 99.9%,
      99.5% and 99.4%). There was no difference in the sensitivity of Syphilis Fast and
      Captia SelectSyph-G on initial (93% vs 92.1%) or repeat (95.6% vs 94.7%) testing:
      both were significantly more sensitive (P<0.001) than the VDRL (46.5% on initial
      and 43.9% on repeat testing). The sensitivities of the Treponema pallidum
      haemagglutination test (TPHA) and FTA-abs were 98.2% and 95.6% respectively.
      Negative reactions in Syphilis Fast and SelectSyph-G were associated with treated
      infections and correlated with low TPHA titres (< or = 80). We conclude that
      Syphilis Fast is a highly specific, simple and fast screening test with a
      sensitivity comparable to native antigen treponemal tests and that it merits
      consideration as a front-line screening test.

PMID- 9598746
TI  - Xanthomonas maltophilia: an emerging pathogen in patients with HIV disease.
AB  - Fifty-four episodes of Xanthomonas maltophilia infection were observed in 52 HIV
      infected patients out of 2062 assessed (2.52%) over a 6-year period:
      sepsis/bacteraemia in 44 cases, lower airways infection in 5 cases, urinary tract
      infection and pharyngitis in 2 cases each, and lymph node involvement in one
      patient. X. maltophilia represented the fourth most common non-mycobacterial
      bacterial pathogen responsible for bacteraemia in HIV-infected patients: 44 cases
      out of 721 diagnosed (6.1%). When compared with non-typhoid Salmonella spp.
      bacteraemia, an increased risk to develop X. maltophilia disseminated infection
      was seen according to the progression of HIV-related immunodeficiency, the
      occurrence of leukopenia-neutropenia, central venous catheterization, previous
      antibiotic and/or corticosteroid treatment, and hospitalization. In 3 patients
      suffering from concurrent AIDS-related disorders, X. maltophilia infection
      contributed to death, while a recurrence occurred in 2 cases only. Due to the
      poor antimicrobial susceptibility of this pathogen (also confirmed in our
      series), X. maltophilia bacteraemia associated with advanced HIV infection and
      concurrent risk factors, may represent a potentially severe disease.

PMID- 9598747
TI  - Examining self-justifications for unsafe sex as a technique of AIDS education:
      the importance of personal relevance.
AB  - In an earlier study, we found that sexual risk-taking in gay men was reduced by
      getting them to evaluate the self-justifications for having unsafe sex which they
      had used on a specific occasion when they 'slipped up' (broke their safe sex
      rules by having unprotected anal intercourse). This study investigated whether
      the earlier finding occurred simply because recalling vividly a specific
      encounter in which a slip-up took place brought the men's risk-taking home to
      them very strongly and whether the intervention would still work if translated
      into posters suitable for the mass media. Gay men (n=92) who had slipped up kept
      diaries of their sexual behaviour for 16 weeks. After 4 weeks, they were
      allocated to one of 3 conditions: Specific Encounter (detailed reconstruction of
      a slip-up, but without any questions about self-justifications); Posters
      (examination of posters, specially designed for the study, that focused on self
      justifications); and Control (no intervention). All 3 groups slipped up to the
      same extent in the post-intervention period. The results for the Specific
      Encounter group indicate that the earlier finding is not attributable to the
      alternative explanation above, while those for the Posters group suggest the
      importance of ensuring personal 'ownership' of the self-justifications presented.
      Implications for AIDS education are discussed.

PMID- 9598749
TI  - Reasons for HIV antibody testing: plus ca change?
AB  - Patient records in a central London genitourinary medicine (GUM) clinic relating
      to HIV testing were examined and compared for the 3 months immediately before and
      after World AIDS Day (WAD) in 1994, according to gender and sexual orientation,
      and the reasons given for testing. Additionally, patient-identified risk was
      compared with counsellor-identified risk in each case in 1994. Findings were
      compared with data from the initial HIV awareness campaign in 1986-87. In the
      1994 study period, there were no significant differences in overall numbers
      attending or gender of test-seekers before and after WAD, or proportions of
      heterosexual, bisexual and gay test-seekers across the time periods. Within each
      of these groups, gay test seekers were significantly more likely to be HIV
      positive than heterosexuals, although there were no differences in numbers found
      positive in each group before and after WAD. Thirty-five per cent (n=268)
      reported a history of safer sex only, 32% (n=247) said 'sometimes', and 33%
      (n=249) said 'no'. Overall, the main reasons given for HIV test-seeking included
      having part of a sexual health screen, having episodes of unprotected sex and/or
      casual partners, concern over partner's status/monogamy, and intravenous drug
      user (IDU) contact. Reasons for testing in 1994 reflected greater awareness of
      HIV transmission compared to 1986-87, although only one-third of those tested
      reported a history of safer sex.

PMID- 9598748
TI  - HIV, hepatitis B and sexual practices in the street-recruited injecting drug
      users of Calcutta: risk perception versus observed risks.
AB  - Injecting drug users (IDUs) were recruited from the streets of Calcutta to obtain
      a baseline biological and behavioural data on risk practices. One-fifth of them
      (mostly using buprenorphine) tested positive for hepatitis B surface antigen
      (HBsAg); 4% were reactive to serologic test for syphilis (VDRL: Venereal Disease
      Research Laboratory). Condom use was insignificant while 74% reported sex with
      female sex workers and 15% of male IDUs also reported having sex with men.
      Although, sharing of injecting equipment ('works') was perceived as dangerous by
      the IDUs, majority of them (90/103) reportedly shared it; cleaning of works
      before sharing was a concern for intravenous but not for intramuscular drug
      injecting. Half of the IDUs reported suffering ever from abscess; a proportion
      (12%) of which had had superadded attack of maggots in it. They were also found
      to be infected with HIV (1%, 95% CI 0.028-5.97%) at a low prevalence that
      prompted subsequent launching of needle syringe exchange programme, establishment
      of cleaning norms before sharing of works, cleaning of injecting site on the body
      and condom promotion.

PMID- 9598750
TI  - Measuring condom use among sex workers in the Dominican Republic.
AB  - The purpose of this paper is to assess the internal consistency of self-reported
      condom use among sex workers in Puerto Plata and Santo Domingo, Dominican
      Republic. We examined the responses to questions about condom use among 4 cross
      sectional samples of sex workers. We compared measures based on: (1) questions
      using always-to-never scales; (2) questions about use with the past 5 clients;
      and (3) questions about use in the past week obtained from a retrospective coital
      log. In each sample, more women reported 'always' using condoms with clients than
      with each of the past 5 clients. In 3 of the 4 samples, only about half of the
      women who reported 'always' using condoms used condoms with the most recent 5
      clients and with all clients in the past week. Internal consistency was
      significantly higher when the comparison was limited to use with the most recent
      5 clients and use in the past week. Self-reported measures of condom use can be
      difficult to interpret. Assessing the internal consistency of several measures of
      use provides insight into the strengths and weaknesses of each measure.

PMID- 9598751
TI  - Intravitreal sustained-release ganciclovir implantation to control
      cytomegalovirus retinitis in AIDS.
AB  - A novel form of therapy, the intravitreal ganciclovir implant (Vitrasert), was
      used to treat cytomegalovirus (CMV) retinitis in AIDS, when it was not possible
      to continue systemic therapy or disease progression was evident despite
      conventional intravenous treatment. A review of the ophthalmic and general health
      data, operative records and fundus photographs of 9 individuals who had Vitrasert
      implantation surgery in Edinburgh. Two patients received bilateral replacement
      implant procedures. Visual acuity, concomitant anti-CMV therapy, complications of
      implantation and control of retinitis were documented until final follow-up.
      Control of CMV retinitis was achieved in all individuals at one month
      postoperatively and remained controlled for a mean period of 5.8 months.
      Postoperative complications were mild and transient in all but 2 eyes of 2
      patients who developed non-progressive macula oedema. Blinding complications as a
      result of surgery were not encountered and retinal detachment was not observed in
      this series. Vitrasert implantation is an acceptable and well tolerated treatment
      for CMV retinitis when systemic therapy fails to control disease progression.

PMID- 9598753
TI  - An unusual aural presentation of Pneumocystis carinii.

PMID- 9598754
TI  - Vulval carcinoma presenting as 'recurrent herpes'.

PMID- 9598752
TI  - High occurrence of HBV among STD clinic attenders in Bombay, India.
AB  - The pattern of sexually transmitted disease (STD) is the basis for designing
      surveillance of specific STD, their trends and syndromic management protocols.
      Two hundred and fifteen consecutive first-time STD clinic attenders at a teaching
      hospital in Bombay were recruited for the study in October 1995. Thorough
      clinical examination and the following investigations were done: wet mount, Gram
      stain, Giemsa stain, modified Thayer-Martin (MTM) medium culture, Fontana stain,
      Venereal Disease Research Laboratory (VDRL), Treponema pallidium
      haemagglutination test (TPHA), HBsAg and HIV. Ulcerative STD constituted 73.5% of
      total STD while 15.8% were discharges and 10.2% were genital growths. Ulcers in
      decreasing order of frequency were chancroid (51.9%), genital herpes (29.1%) and
      syphilis (14.5). 76.5% of genital discharges were due to gonococcal infection.
      The high rate of ulcerative STD is possibly an important co-factor for the high
      HIV prevalence of 31.2% in Bombay. Of 182 patients tested for HBV, 16 (8.8%) were
      reactive for HBsAg, revealing a high prevalence among STD attenders. A high co
      relation of HBsAg positive with either HIV or VDRL requires urgent attention for
      HBV intervention strategies in this population.

PMID- 9598755
TI  - Audit of service to a minority client group: male to female transsexuals.
AB  - Male to female transsexual clients are a group of clients for whom there are few
      dedicated services in New Zealand. To examine service utilization in Wellington,
      New Zealand, 70 male to female transsexual clients were identified and their
      medical records audited for selected aspects of sexual health service delivery.
      Audit revealed that sexual health history is recorded incompletely and
      behavioural risk factors are not fully explored, sexual health examination and
      testing is incomplete. We conclude opportunities to expose relevant behavioural
      factors and to educate for sexual safety and health promotion are lost with this
      infrequently attending minority client group.

PMID- 9598756
TI  - What advice is given to patients with a new diagnosis of genital warts?

PMID- 9598757
TI  - Concurrent partnerships, ethnicity, STD and HIV.

PMID- 9598758
TI  - The value of renal biopsy in the investigation of isolated microscopic
      haematuria.

PMID- 9598759
TI  - Use and abuse of intracavernosal injections.

PMID- 9598760
TI  - Female street prostitutes in Middlesbrough, England.

PMID- 9598761
TI  - HIV-2 in pregnancy: to treat or not to treat?

PMID- 9598762
TI  - Rationale, design and methods of a study on micronutrient status among adults.
AB  - OBJECTIVE: To describe the rationale, design and methods for a nutrition
      surveillance study with special reference to vitamin B6 and other micronutrients.
      RATIONALE AND DESIGN: Several studies in the Netherlands have shown that
      differences in dietary intake and in nutritional status indicators are relatively
      small among various socio-demographic groups, so that the relevance of this
      traditional risk group identification in terms of public health and nutrition
      policy is limited. Therefore, it was decided to use the diet itself as primary
      selection criterion for a study on the adequacy of the vitamin B6 supply. The
      first Dutch national food consumption survey in 1987/88 showed, among other
      things, that mean vitamin B6 intake (per gram of protein) was substantially below
      the adequate level for all age-gender groups studied. Since the potential impact
      on public health of this observation may be relatively large, intake of vitamin
      B6 was chosen as first selection criterion. A study design that creates the
      largest possible distinction in vitamin B6 intake would be most efficient to
      study the health risks as a consequence of a low vitamin B6 intake. Several
      arguments, such as the need to estimate the prevalence of an inadequate status of
      vitamin B6 and other micronutrients, led to the decision to use a random
      population sample as a reference group for comparison with the group with low
      habitual vitamin B6 intake. Other major arguments underlying the study design and
      the selection of the nutritional status indicators, as well as the framework of
      the Dutch Nutrition Surveillance System, are discussed. Finally, the design and
      methods of the study are described in detail (except food consumption methods).

PMID- 9598763
TI  - Food consumption methods. Development, reproducibility and validation of a food
      frequency questionnaire for vitamin B6.
AB  - OBJECTIVE: The correct classification of adults with a habitual low vitamin B6
      intake by means of a food frequency questionnaire (FFQ). Assessment of
      reproducibility of the food frequency questionnaire and of the relative validity
      as compared to 3 d diet records (DR). DESIGN: A self-administered food frequency
      questionnaire (FFQ) to measure habitual vitamin B6 intake was developed using the
      data base of the first Dutch National Food Consumption Survey 1987/88 (DNFCS).
      The frequency and quantity of consumption of 92 (combinations of) food products,
      contributing to about 95% of vitamin B6 intake, were asked for. Recent food
      consumption was measured with 3 d diet records. Reproducibility of the FFQ was
      assessed after 10 months (n = 330). SUBJECTS: Randomly selected men and women
      aged 20-79 y, stratified for 10 y age classes and sex. RESULTS: A total number of
      2867 FFQs was adequately completed (response rate 46%). A low vitamin B6 group
      was selected from the lowest tertile of age-gender specific vitamin B6 intake (36
      men and 36 women, aged 20-49 and 36 men and 36 women, aged 50-79) and a so-called
      reference group (n = 300) was selected at random. The ratio of vitamin B6 intake
      according to FFQ and DR (FFQ/DR) varied between 0.77 and 0.99 for the various age
      gender-study groups; for vitamin B6/g protein the FFQ/DR ratio varied between
      1.00 and 1.10. After correction for intraindividual variance Pearson correlation
      coefficients between vitamin B6 intake according to FFQ and DR varied between
      0.27 and 0.95 for the various age-gender-study groups, for vitamin B6/g protein
      the corrected Pearson correlation coefficients varied between 0.27 and 0.65. Of
      the subjects selected in the low B6 groups, 61-81% fell in the lowest tertile of
      vitamin B6 intake according to diet records and 3-6% fell in the extreme opposite
      tertile. The percentage subjects selected in the same/opposite quartile of
      vitamin B6 intake according to FFQ and DR was 50/11 for men, and 45/18 for women.
      Pearson correlation coefficients for vitamin B6 intake according to the first and
      the second FFQ were 0.64 and 0.72 for men and women, respectively; for vitamin
      B6/g protein these values were 0.70 and 0.51 for men and women, respectively. The
      proportion of subjects classified in the same/extreme opposite tertile of vitamin
      B6 intake was 56/6 and 62/5 for men and women, respectively. CONCLUSIONS: It is
      concluded that the FFQ was adequate for the selection of subjects with a
      habitually low vitamin B6 intake.

PMID- 9598765
TI  - Dietary intake among adults with special reference to vitamin B6.
AB  - OBJECTIVE: To assess the adequacy of the dietary intake in general, and that of
      vitamin B6 intake especially. DESIGN AND SUBJECTS: Dietary intake based on 3 d
      diet-records was assessed among a random sample of the adult Dutch population
      (the reference group, n = 300) aged 20-79 y, stratified for age and gender and
      among a group with a low vitamin B6 intake, selected by means of a food frequency
      questionnaire. RESULTS: Among the reference group, absolute vitamin B6 intake on
      average amply met the RDA in all age-gender categories, whereas the adequate
      level of 20 microg vitamin B6 per gram protein, was on average met by men only.
      The prevalences of a vitamin B6 intake below the minimum requirement (absolute)
      of 1 mg/d was 1-11% and below the average minimum requirement of 15 microg/g
      protein was 5-12% for the various age-sex reference groups. Average intake of
      folate among women of childbearing age did not meet the recommendation of 400
      microg/d for those who want to become pregnant. Average intake of iron and iodine
      was also below recommended levels among women aged 20-49 y. Both absolute vitamin
      B6 intake and the vitamin B6/protein ratio calculated with the diet records was
      lower among the low vitamin B6 groups than among the reference groups, indicating
      that the preselection of groups with low vitamin B6 intakes on the basis of a
      food frequency questionnaire was successful. Intake of energy and macro- and
      micronutrients, as well as a nutrient density of the diet were lower among low
      vitamin B6 groups than among reference groups. CONCLUSIONS: It is concluded that
      a low vitamin B6 intake is the result of both the quantity (energy) and quality
      (nutrient density) of the food consumed. The effects of this are not restricted
      to vitamin B6 and therefore, the low vitamin B6 groups have a combination of
      relatively low intakes.

PMID- 9598764
TI  - The study population: general characteristics and potential confounding factors.
AB  - OBJECTIVE: To test the representativity of the study population and to identify
      potential selection bias. DESIGN: Non-response analysis and comparison with other
      representative samples from the Dutch population. Description of physical and
      clinical biochemical variables as well as health and lifestyle characteristics
      among low vitamin B6 groups and reference groups. RESULTS AND CONCLUSIONS: The
      non-response rate for the food frequency questionnaire was 54%; subsequently, non
      response for the detail study was 42%. A greater proportion of respondents to the
      FFQ and of participants in the reference group of the study followed a special
      dietary regimen or a therapeutic diet or used dietary supplements compared with
      non-respondents, indicating that we may have selected a somewhat more health
      conscious reference group. There were no differences in vitamin B6 intake
      (absolute or per g protein) between participants and the total group of non
      respondents for the detail study. Selection of a low B6 group did not result in
      important bias regarding physical, biochemical or general health and lifestyle
      characteristics. Exceptions were a difference in the proportion of dieters
      (younger women) and supplement users (older women) and a difference in creatinine
      clearance and supplement use between reference and low B6 groups. The differences
      found, however, were small. Nonetheless, these factors have to be taken into
      account when analysing and interpreting the results.

PMID- 9598766
TI  - Micronutrient status, with special reference to vitamin B6.
AB  - OBJECTIVE: To assess the adequacy of micronutrient status among the adult
      population, with special reference to vitamin B6 status. DESIGN AND SUBJECTS:
      Micronutrient status was assessed among a random sample of the adult Dutch
      population (reference group, n = 300), aged 20-79 y, stratified for age and
      gender, and among a group with a low vitamin B6 intake (n = 144). RESULTS: Low
      vitamin B6 groups had lower mean levels of erythrocyte and plasma pyridoxal (PL)
      and pyridoxal-5'-phosphate (PLP), urinary excretion of 4-pyridoxic acid, basal
      and stimulated erythrocyte aspartate aminotransferase (EAST) and erythrocyte
      alanine aminotransferase (EALT) activities and EAST stimulation coefficients but
      not of EALT stimulation coefficients, handgripstrength and 24 h homocysteine
      excretion before and after a methionin load test. Besides, plasma levels of
      vitamin C, B12 and folate were lower among low B6 than among reference groups
      indicating a combined low vitamin status. Direct biomarkers of vitamin B6 intake
      (plasma PLP and 4-pyridoxic acid excretion) were significantly related to more
      functional parameters (EAST, EALT and alpha-EAST). Among random reference groups
      the prevalence of plasma PLP values below 19 nmol/l was 3-7% for different age
      gender groups, with the highest value of 16% among men aged 50-79 years. The
      prevalence of high values of erythrocyte glutathion reductase stimulation
      coefficient (alpha-EGR) and low levels of serum vitamin B12 and C was not more
      than 5% among different age-gender reference groups. CONCLUSIONS: Direct
      biomarkers of vitamin B6 intake confirmed the preselection of a group with a low
      vitamin B6 intake. The results suggest that the sensitivity of vitamin B6 status
      parameters for low vitamin B6 intake was highest for the direct vitamin B6 status
      parameters and lowest for handgripstrength and homocysteine excretion after a
      methionin load; results for enzyme stimulation coefficients were intermediate.
      The prevalence of below adequate status parameters for vitamin B2, B6, B12 and C
      was not more than 7% among the different age-gender groups, with the exception of
      a value of 16% for plasma PLP levels below 19 nmol/l among men aged 50-79.

PMID- 9598768
TI  - Folate intake and status among adults in the Netherlands.
AB  - OBJECTIVE: To assess the adequacy of folate intake and status among adults in the
      Netherlands. DESIGN AND SUBJECTS: Dietary intake was measured by 3 d diet records
      among 444 adults, aged 20-79 y, stratified for sex and 10 y age classes, with an
      overrepresentation of people with a low habitual intake of vitamin B6. Serum
      folate and other physical, biochemical and lifestyle characteristics were
      determined, and interrelationships were evaluated by bi- and multivariate
      regression analysis. RESULTS: Mean folate intake was 325 and 308 microg/d in men
      aged 20-49 and 50-79 y, respectively. In both younger and older women mean folate
      intake was 270 microg/d. The prevalence of intakes below the lower limit of the
      recommended range (200-300 microg/d) was 10-20% among different age-gender
      groups. No intakes below the average minimum requirement of 100 microg/d were
      observed. The recommendation of 400 microg folate/d for women who wish to become
      pregnant was not met by 95% of the women aged 20-49 y. Potatoes, vegetables and
      fruit provided 36% of folate in the diet; other important sources were bread
      (18%) and dairy products (16%). Mean serum folate levels were 11.3 and 12.1
      nmol/l in younger and older men, respectively. In younger and older women these
      levels were 12.2 and 14.2 nmol/l, respectively. Serum folate levels below 5
      nmol/l (the 2.5 percentile of healthy blood donors) were present in 4% of the
      older men, but not in the other age-gender-groups. Serum folate levels were
      clearly influenced by recent folate intake. Furthermore, physiological and
      lifestyle variables, notably alcohol and tobacco use, were important determinants
      of serum folate. CONCLUSION: The folate intake among adult men and women was
      adequate in view of recommended daily intakes. However, the folate intake among
      women did not meet the recommendation for those who want to become pregnant.
      According to criteria derived from homocysteine metabolism as related to
      cardiovascular disease, folate status may not be adequate in 60-79% of adult age
      sex groups.

PMID- 9598767
TI  - Dietary and other determinants of vitamin B6 parameters.
AB  - OBJECTIVE: To assess the dietary, physical, biochemical and lifestyle
      determinants of vitamin B6 status parameters among healthy adults. DESIGN AND
      SUBJECTS: Dietary intake and status variables as well as other relevant
      characteristics were determined among 444 adults, aged 20-79 y and stratified for
      sex and 10-years age classes with a randomly selected control group (n = 300) and
      an over representation of persons with a low habitual vitamin B6 intake (n =
      144). RESULTS AND CONCLUSIONS: The direct status parameters (plasma pyridoxal-5'
      phosphate (PLP), plasma pyridoxal + PLP (PL + PLP), and 4-pyridoxic acid (4-PA)
      excretion) were clearly related to dietary variables and plasma concentrations of
      vitamin C (women only), vitamin B12 and folate. The total percentage of variance
      in p-PLP explained in multivariate regression analysis was 41 and 30% in men and
      women, respectively. The most important explaining variables besides vitamin B6
      intakes were variables closely related to PLP-metabolism: albumin and alkaline
      phosphatase. Biochemical function related status parameters showed less
      statistically significant correlations with dietary variables. Four to 24% of the
      variance in the stimulation coefficients of erythrocyte aspartate
      aminotransferase (alpha-EAST) and erythrocyte alanine aminotransferase (alpha
      EALT) and change in homocysteine excretion after a methionin load was explained
      by a combination of dietary, physiological and lifestyle related variables. The
      low percentages explained for some variables, notably alpha-EAST (women) and the
      change in homocysteine excretion after a methionin load (men), suggests that
      these parameters are not sensitive to the level of vitamin B6 intake as found in
      the present study. Alcohol contributed in many of the explaining models for
      vitamin B6 status parameters. Therefore, when assessing the vitamin B6 status of
      a population, it is important to estimate the level of alcohol intake as well.
      Furthermore, the results illustrate the importance of sex related differences in
      the metabolism of some parameters, especially homocysteine excretion. The
      variance in the clinical function related status parameter measured in the
      present study, handgripstrength, was explained for 50% by a combination of age,
      body weight and Quetelet Index (QI) with no important contribution of dietary
      variables.

PMID- 9598769
TI  - Iron intake and iron status among adults in the Netherlands.
AB  - OBJECTIVE: To assess the adequacy of iron intake and status, the prevalence of
      marginal iron status, the physiological and lifestyle factors influencing iron
      status and the role of dietary factors affecting the bioavailability of iron
      among Dutch adults. DESIGN: Food consumption was measured with 3 d diet records.
      Iron status and prevalence of iron deficiency and iron accumulation were
      evaluated using different criteria. Physical, biochemical and lifestyle
      characteristics were determined and relationships with iron status were evaluated
      by bi- and multivariate regression analysis. SUBJECTS: A sample of 444 adults,
      aged 20-79 y stratified for sex and 10 y age classes, with an overrepresentation
      of people with a low habitual intake of vitamin B6. RESULTS: Average iron intake
      was higher than the recommended daily allowance for the Netherlands in all sex
      age groups except women aged 20-49, in which group average iron intake was 23%
      below the recommendation. Early iron deficiency, as reflected in low ferritin
      levels, was not found among men aged 20-49, but was observed in 5% of women aged
      50-79, 11% of men aged 50-79, and 16% of women aged 20-49. Iron deficiency
      anaemia as reflected in low haemoglobin levels was found in 0-5% of the age-sex
      groups. Among men and women, 16% and 13% of variance in haemoglobin level,
      respectively, could be explained by physiological and dietary factors. For
      ferritin, the proportions were 36% and 34%, respectively. Iron status was
      correlated negatively with the vegetable fraction of the diet, and positively
      with factors from the animal fraction (haem iron, animal protein, meat). Further,
      haemoglobin was positively correlated with body weight among men, and with both
      age and use of oral contraceptives among women. Both among men and women, blood
      donorship in the six months prior to the study was negatively associated with
      serum ferritin levels. CONCLUSIONS: Women aged 20-49 are the adult sex-age group
      with the greatest risk of developing (an early stage of) iron depletion. The most
      important dietary factors influencing the iron status are the type of iron
      (haem/non-haem) and factors affecting the bioavailability of iron.

PMID- 9598770
TI  - Iodine intake and urinary excretion among adults in the Netherlands.
AB  - OBJECTIVE: To assess the prevalence of low and marginal iodine intake and urinary
      iodine excretion among adults in the Netherlands and to investigate determinants
      of urinary iodine excretion. DESIGN AND SUBJECTS: The study population consisted
      of 444 people aged 20-79 y, balanced for sex and 10 y age classes with an over
      representation of people with a low habitual intake of vitamin B6. Food
      consumption was measured by three day food records and 24 h urine was sampled
      twice. RESULTS AND CONCLUSIONS: On average, iodine intake (mean of three days) in
      men was in the recommended range of 150-300 microg/d, but average intake in women
      was not. Mean 24 h urinary excretion values confirmed this observation.
      Estimation of the prevalence of low iodine excretion depended on the parameter
      chosen (absolute per 24 h, per kg body weight per 24 h, as concentration or per
      creatinin). The prevalence of low iodine supply, based on intake <100 microg/d
      (mean of three days) and intake or excretion parameters per creatinin excretion
      or per kg body weight, varied from 4-14% among adult women and from 5-17% among
      adult men. The prevalence of marginal iodine intake (<50 microg/d) and excretion
      was less than 5% in all adult age-sex groups. Urinary iodine excretion was most
      strongly associated with intake of iodine as such or as bread in combination with
      urinary excretion of sodium or potassium, confirming the importance of iodized
      salt (in bread) for iodine status. Age and total energy intake had a relatively
      minor impact on urinary iodine excretion.

PMID- 9598771
TI  - An effective way to identify dietary risks among adults--general discussion and
      conclusions.
AB  - OBJECTIVE: To identify dietary risks among adults in the Netherlands, with
      special reference to micronutrient intake, more specifically vitamin B6, folate,
      iron and iodine. DESIGN AND SUBJECTS: Dietary intake, nutritional status and
      other physiological and lifestyle characteristics were measured among 444 adults,
      aged 20-79 y, stratified for 10 y age-classes and sex, with an overrepresentation
      of subjects with a habitual low intake of vitamin B6. DISCUSSION AND CONCLUSION:
      A general discussion of the study design and possible selection bias.
      Identification of groups at risk and the possible impact of low intake of several
      micronutrients. A discussion of dietary and other determinants of micronutrient
      status parameters. The results of the present survey suggest that even at vitamin
      B6 intakes in the lower tertile of the intake range there is no great effect on
      biochemical functioning. However, blood vitamin levels may not be optimal with
      regard to cardiovascular risk among a non-negligible part of the population and a
      recommendation for an adequate vitamin intake seems warranted, despite the many
      uncertainties concerning the relationship between vitamin intake and
      cardiovascular risk. Furthermore, the results of the present survey stress the
      importance of adequate dietary advice for women of childbearing age.

PMID- 9598772
TI  - The consequences of antibiotic use in horticulture.

PMID- 9598773
TI  - Clinical trials of antibacterial agents--a commentary.

PMID- 9598775
TI  - Comparative in-vitro activity of cefpirome against isolates from intensive care
      and haematology/oncology units. Belgian Multicentre Study Group.
AB  - The susceptibility of 389 Enterobacteriaceae, 231 other Gram-negative bacilli
      (including 150 Pseudomonas aeruginosa) and 233 Gram-positive organisms was
      determined by the NCCLS reference microdilution technique against cefpirome and
      other antibiotics. Cefpirome and cefepime were the most active compounds against
      Enterobacteriaceae, including potentially beta-lactamase-inducible species. The
      MIC90 of cefpirome against potentially inducible and non-inducible species of
      Enterobacteriaceae was 2 mg/L and 0.5 mg/L, respectively. Ceftazidime, cefpirome
      and cefepime had similar activity against P. aeruginosa, with MIC90s of 64 mg/L,
      64 mg/L and 32 mg/L, respectively. Cefpirome and cefepime had similar activity
      against Gram-positive cocci, with MIC90s of 1 mg/L and 2 mg/L, respectively,
      against oxacillin-susceptible Staphylococcus aureus and 64 mg/L and 128 mg/L,
      respectively, against Enterococcus spp.; both had an MIC90 of 1 mg/L against
      Streptococcus pneumoniae. This study shows that fourth-generation cephalosporins,
      such as cefpirome, could be useful in haematology/oncology units and, in
      particular, ICUs where high resistance rates are observed.

PMID- 9598774
TI  - An in-vitro study of carbapenem-induced morphological changes and endotoxin
      release in clinical isolates of gram-negative bacilli.
AB  - One hundred clinical isolates, including Escherichia coli, Serratia marcescens,
      Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris and Proteus
      mirabilis, were exposed to carbapenems (imipenem, panipenem, meropenem and
      biapenem) at 0.5 x MIC for 3 h, then their morphology was examined and endotoxin
      release determined. Ceftazidime, which induces filament formation, was used as a
      control. Scanning electron microscopy showed that these carbapenems induced
      formation of spherical or ovoid cells, except for P. aeruginosa treated with
      meropenem and biapenem; these latter cells had a 'bulge' midway along them and we
      have termed them 'oval-centred'. There was a relationship between morphology and
      the amount of endotoxin released following exposure to carbapenems or
      ceftazidime. Of all the species investigated, P. aeruginosa showed the most
      variable morphological changes. P. aeruginosa exposed to biapenem were longer
      oval-centred in shape, and released significantly more endotoxin than those
      exposed to imipenem, panipenem (spherical) or meropenem (shorter oval-centred
      cells) (P=0.030, 0.017 and 0.002, respectively). In all strains except P.
      aeruginosa, carbapenems induced significantly less endotoxin release than
      ceftazidime (P < 0.05).

PMID- 9598776
TI  - Pharmacodynamics of penicillin are unaffected by bacterial growth phases of
      Streptococcus pneumoniae in the mouse peritonitis model.
AB  - The correlation between pharmacokinetic parameters and the in-vivo effect of
      antibiotics in relation to bacterial growth phases was evaluated using the mouse
      peritonitis model with a penicillin-resistant pneumococcus. Different 8 h dosing
      regimens were applied, with different total doses and initiated at different
      times during the bacterial growth phase. The effect was measured as the decline
      in bacterial counts in the peritoneal cavity. The pharmacokinetic parameters
      showed major changes during the phases of growth, as the serum elimination of
      penicillin decreased during the infection. The same effect of dosing regimens was
      observed in the exponential and stationary phases. In two regimens where T(>MIC)
      (the time the serum concentration exceeded the MIC) was 50% of the treatment
      period, a significantly better effect was achieved with a 2 hourly regimen than
      with a regimen with treatments every 20 min. The T(>MIC) of each dose was shown
      to be a critical parameter for achieving an effect in all growth phases. The
      maximum effect of penicillin, a 5-6 x log10 decline in bacterial counts in the
      peritoneum of the mice, was achieved when T(>MIC) was >50% of the treatment time
      or longer than approximately 40 min of each dose. The 50% effective dose for
      protection after a single injection, ED50, was measured in the different phases
      of the infection and found to increase with the duration of the pneumococcal
      infection, while mice treated 24 h after challenge were beyond therapeutic range.
      The correlation between the effect of penicillin and pharmacokinetic parameters
      appears to follow the same rules during the different in-vivo growth phases of
      pneumococci.

PMID- 9598777
TI  - The efficacy of ciprofloxacin and doxycycline against experimental tularaemia.
AB  - The efficacy of doxycycline and ciprofloxacin against an experimental tularaemia
      infection was assessed by comparing the median lethal dose (MLD) of Francisella
      tularensis Schu4 biotype A strain given intraperitoneally to antibiotic-treated
      and untreated mice. In untreated Porton outbred mice this was <1 cfu.
      Ciprofloxacin and doxycycline given at 40 mg/kg bd, initiated 48 h before
      infection and continued for 5 days after infection, afforded protection against
      intraperitoneal challenges of 3.7 x 10(6) cfu and 6.0 x 10(6) cfu, respectively.
      Protection was reduced when both antibiotics were given over a similar period at
      a lower dose regimen (20 mg/kg bd) to 8.8 x 10(5) cfu and 3.5 x 10(2) cfu,
      respectively. The greater reduction in protection offered by doxycycline was a
      reflection of the higher in-vitro MIC. Protection also decreased when the
      antibiotics were initiated 24 h after challenge. The MLD was 3.2 x 10(5) cfu and
      1.6 x 10(6) cfu for ciprofloxacin and doxycycline respectively given at 40 mg/kg
      bd and was reduced further using the lower dose regimen. Overall, 90% of the
      deaths occurred following the withdrawal of antibiotic, irrespective of the
      antibiotic dose or type. It was possible to prevent this relapse by extending the
      antibiotic administration to 10 days after challenge. Ciprofloxacin and
      doxycycline may be useful for treating tularaemia, although the possibility of
      relapse should be considered.

PMID- 9598778
TI  - Clinical trials of antibacterial agents: a practical guide to design and
      analysis. Statisticians in the Pharmaceutical Industry Working Party.
AB  - Guidelines on the conduct of clinical trials of antibacterial agents produced by
      the US Food and Drug Administration, the British Society for Antimicrobial
      Chemotherapy, the Infectious Diseases Society of America and a European Working
      Party have been reviewed. Although very informative, these guidelines provide
      limited practical guidance on the design and statistical aspects of phase III
      studies of antimicrobial agents. This paper describes the differences between
      antibacterial trials and clinical studies in other therapeutic areas with regard
      to subjective endpoints, dual clinical and bacteriological endpoints, frequent
      protocol violations and difficulty of using placebo controls. The importance of a
      detailed protocol and planned analysis strategy is emphasized. The choice of
      comparator agents, practical issues with the blinding of trial materials and the
      documentation of patients excluded from study entry are discussed. The use of
      different patient groups and different endpoints in analyses are described. The
      principles of equivalence and their application to trials of antibacterial agents
      are discussed, together with an approach to calculating sample size. A variety of
      statistical analyses of results are compared for different situations indicating
      some of the problems that can arise. Different methods of presentation of study
      data are included with emphasis on regulatory submissions rather than scientific
      publications. Some graphical presentations are recommended and issues regarding
      data across different studies are discussed.

PMID- 9598779
TI  - Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and
      moxifloxacin (BAY 12-8039) MICs and mutations in grlA, grlB, gyrA and gyrB in 116
      unrelated clinical isolates of Staphylococcus aureus.
AB  - The in-vitro activities of five fluoroquinolones were tested against 70
      ciprofloxacin-resistant and 46 ciprofloxacin-susceptible unrelated isolates of
      Staphylococcus aureus. All 116 S. aureus isolates were studied for the presence
      of mutations in the grl and gyr loci. The order of efficacy of the
      fluoroquinolones tested, from least to most active, was: ciprofloxacin,
      ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039), in response
      to all characterized mutations in grlA, grlB, gyrA and gyrB. Moxifloxacin was
      active against most S. aureus isolates tested (MIC90 = 1 mg/L for ciprofloxacin
      resistant isolates) and was less influenced by known mutations.

PMID- 9598780
TI  - Serum bactericidal activity of newer oral cephalosporins in healthy volunteers.
AB  - The serum bactericidal activity of three oral cephalosporins was studied in 12
      volunteers, after administration of single doses of cefuroxime axetil 250 mg,
      cefixime 200 mg, cefixime 400 mg and cefetamet pivoxil 500 mg. Serum bactericidal
      activity against clinical isolates of Streptococcus pyogenes, Streptococcus
      pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae was measured by a
      standardized microdilution method. Cefuroxime axetil demonstrated the best
      bactericidal activity against Gram-positive organisms and cefixime was the most
      bactericidal against Gram-negative bacteria.

PMID- 9598781
TI  - Bacterial interference in the nasopharynx following antimicrobial therapy of
      acute otitis media.
AB  - The effect on the nasopharyngeal bacterial flora of therapy for 10 days with co
      amoxiclav or cefprozil was studied in 50 children with acute otitis media. Before
      therapy, potential pathogens (Streptococcus pneumoniae, Haemophilus influenzae
      and Moraxella catarrhalis) were isolated in 14 (56%) of those treated with co
      amoxiclav and 15 (60%) of those treated with cefprozil. Following therapy, the
      reduction in the number of these pathogens was the same in the two groups.
      However, differences between the groups were noted in the recovery of organisms
      with interfering capability, namely alpha-haemolytic streptococci,
      Peptostreptococcus anaerobius and Prevotella melaninogenica. Fifty interfering
      organisms were recovered from each group before therapy. After therapy with co
      amoxiclav or cefprozil their number declined to 11 and 42, respectively (P<
      0.001).

PMID- 9598782
TI  - Aztreonam-clavulanic acid synergy does not mean extended-spectrum beta-lactamase
      in Stenotrophomonas maltophilia.

PMID- 9598783
TI  - In-vitro activity of the combination of colistin and rifampicin against multidrug
      resistant strains of Acinetobacter baumannii.

PMID- 9598784
TI  - A newly recognized acetylated metabolite of arbekacin in arbekacin-resistant
      strains of methicillin-resistant Staphylococcus aureus.

PMID- 9598785
TI  - The challenge of the global elimination of iodine deficiency disorders.
AB  - Most nations of the world are well positioned for success in their pursuit of the
      virtual elimination of iodine deficiency disorders (IDD) by the year 2000. In
      1990 at the World Summit for Children, Heads of State and Government had agreed
      on this global goal and in 1992 at the International Conference on Nutrition,
      multi-sector country delegations from all over the world developed the prototype
      framework for national action. Following a special recommendation of the United
      Nations Joint Committee on Health Policy, universal salt iodization (USI) is now
      being applied in almost all countries with an IDD problem recognized as being of
      public health significance. The core components of national IDD programmes based
      on USI are presented in this paper, and examples are given of effective actions
      ongoing in a number of countries. While in principle all components such as
      communications, information management and laboratory support should integrate
      and complement with ongoing efforts for general nutritional improvement, national
      IDD programmes also have specific needs which require separate arrangements.
      Sources of support and information, available from the international public
      nutrition community are indicated. The global conquest of IDD provides an example
      for other effective public nutrition practices from the important lessons that
      are being learned. Particularly, the role of the private food sector as full
      partner in national programmes is relevant to ongoing and future attempts to
      reduce and eliminate other major global malnutrition problems.

PMID- 9598786
TI  - Prevention and control of iodine deficiency: a review of a study on the
      effectiveness of oral iodized oil in Malawi.
AB  - Unfortunately there will always be groups of people who will not have access to
      iodized salt as a measure for iodine deficiency control. Iodized oil for oral use
      may be indispensable for them. The conclusions of a study in Malawi on the
      effectiveness of oral iodized are that the type of iodized oil, goitre,
      intestinal parasites, sex, adipose tissue, cassava consumption and seasonality
      are factors which influence the duration of effectiveness of this prophylaxis
      measure. The study in Malawi used urinary iodine concentration as a measure for
      iodine status and a hyperbolic function to describe the pattern of urinary iodine
      excretion after oral dosing. Cumulative frequency distributions of individually
      assessed durations of effectiveness very conveniently describe the prevalence
      rate of iodine deficiency after oral iodized oil administration. They are very
      useful for identifying factors which influence the effectiveness of oral iodized
      oil and may thus be a tool for optimizing iodized oil programmes.

PMID- 9598787
TI  - Adequacy of the iodine supply in The Netherlands.
AB  - OBJECTIVE: To assess the adequacy of the iodine supply in the Netherlands and to
      study possible ways of increasing the iodine intake. DESIGN, SETTINGS AND
      SUBJECTS: Goitre and nutrition surveillance studies (intake and urinary excretion
      of iodine) among population groups (age: 12-85 y, n=57-1704) in the Netherlands
      in the period 1981-1993. Simulation studies, based on the Dutch Nutrition Food
      Consumption Surveys (n=6000), calculating iodine intake among population groups
      after fictively iodizing different food groups. RESULTS: Mean intake of iodine,
      measured with different food consumption methods in the period 1984-1993, met the
      recommended amount of 150-300 microg per day in males, but not in females. Median
      urinary iodine excretion levels were in the range for mild Iodine Deficiency
      Disorders in both sexes. According to dietary methods reflecting habitual intake
      and urinary iodine excretion per kg body weight or per mmol creatinin the
      prevalence of low iodine supply among adults is between 4 and 20% for women and
      between 5 and 15% for men. Iodization of different products would increase mean
      iodine intakes by up to 45% and would give a reduction of roughly 65% in the
      prevalence of low iodine intakes. CONCLUSION: The present goitre prophylaxis in
      the Netherlands is not optimally effective. The iodine supply is below cut-off
      points in 4-20% of the adult population. It is possible to decrease the
      prevalence of low iodine intakes without a clear risk of exceeding the maximum
      acceptable daily iodine intake by increasing the iodine content of baker's salt
      and/or by adding iodine to other foods.

PMID- 9598788
TI  - The challenge of improving iron nutrition: limitations and potentials of major
      intervention approaches.
AB  - Various approaches to improving iron status are discussed. Success in controlling
      iron deficiency worldwide will require the exploration and demonstration of all
      possible options. The approaches, which are not mutually exclusive, include iron
      supplementation, nutrition education, reducing intestinal parasites (particularly
      hookworm), expanding fortification of processed foods, and developing crops that
      are more iron bioavailable. Coordination with existing health and nutrition
      programs can enhance progress toward better overall nutrition. For example, in
      the development of food fortification or of crops with higher nutritional value,
      the combination of multiple micronutrients can be considered. Within the primary
      health care system, iron supplementation and deworming can be coordinated with
      other health care activities. The ultimate success in control of iron deficiency
      will depend on how well the various intervention approaches can be integrated
      within the current framework of public health, food processing, and agriculture
      development.

PMID- 9598789
TI  - Technological approaches to combatting iron deficiency.
AB  - Iron deficiency is widespread among young children and women of reproductive age,
      especially in less industrialized countries. It is partly induced by plant-based
      diets containing low levels of poorly bioavailable iron. The most effective
      technological approaches to combat iron deficiency in less industrialized
      countries include supplementation targeted to high risk groups combined with a
      national program of food fortification and dietary strategies designed to
      maximize the bioavailability of both the fortificant and the intrinsic food iron.
      Prerequisites for effective supplementation include an efficient and consistent
      supply, delivery, and consumption of a highly bioavailable iron supplement.
      Fortification relies less heavily on compliance and an organized health service
      but must be regulated by government to eliminate competition with unfortified
      products. To be effective, a combination of an iron fortificant and food vehicle
      must be selected which is safe, acceptable to and consumed by the target
      population, does not adversely effect the organoleptic qualities and shelf-life
      of the food vehicle, and provides iron in a stable, highly bioavailable form.
      Bioavailability of both the fortificant and the intrinsic food iron can be
      improved by adding enhancing factors, removing inhibitors such as phytate by
      enzymatic and non-enzymatic hydrolysis, and using 'protected' fortification
      compounds.

PMID- 9598790
TI  - A sustainable solution for dietary iron deficiency through plant biotechnology
      and breeding to increase seed ferritin control.
AB  - OBJECTIVES: To stimulate novel sustainable solutions to the problem of the
      nutritional iron deficiency, we asked: How does Nature insure proper iron
      nutrition of embryos and neonatal animals? Estimates of iron deficiency world
      wide are 30% of the population, with women and children at the greatest risk.
      Recent studies linking iron deficiency with impeded cognitive development
      emphasizes the enormity of the impact of iron deficiency. Sustainable solutions
      to the problem of dietary iron deficiency have been elusive. RESULTS: Data for
      storage iron was examined in seeds, developing plants, embryos and developing
      animals. In all cases, the common source of stored iron for development was
      ferritin. The protein component of ferritin concentrates iron billions of times
      above the solubility of the free metal ion. High conservation of ferritin
      sequences in bacteria, plants and animals and the specificity of ferritin
      bioavailability either added extrinsically or intrinsically enriched in a
      selected soybean cultivar, showed high efficacy in curing dietary iron deficiency
      in the rat model. Older data on ferritin were reevaluated in light of
      contemporary knowledge. CONCLUSIONS: Enhancement of natural seed ferritin content
      by biotechnology and breeding has the potential for a sustainable solution to the
      problem of global dietary iron deficiency.

PMID- 9598792
TI  - Agronomic problems related to provitamin A carotenoid-rich plants.
AB  - OBJECTIVES: Review how agricultural systems might be changed to increase the
      vitamin A density of diets in developing countries to provide sustainable
      solutions to vitamin A deficiency globally. DESIGN: Develop agricultural systems
      that not only assure calorie adequacy for people, but also address vitamin A
      density in diets. SETTINGS: Agricultural systems could be modified in some
      developing nations in ways that would provide adequate dietary amounts of
      provitamin A carotenoids from plant food sources. SUBJECTS: Infants and children
      of low-income families are most at risk of developing vitamin A deficiency in
      developing countries. INTERVENTIONS: Cropping systems could be modified to
      include more vegetable and fruit crops containing higher bioavailable amounts of
      provitamin A carotenoids in some countries. Additionally, cultural practices
      could be modified through education, agricultural extension and/or social
      marketing to insure that the bioavailable provitamin A carotenoid levels in food
      crops are optimized. Staple food crops could be improved as sources of provitamin
      A carotenoids by traditional plant breeding and/or by genetic engineering
      efforts. RESULTS: Currently, many techniques are available to increase the
      vitamin A content of diets through sustainable food-based approaches.
      Agricultural approaches should be examined closely to finding sustainable food
      based system solutions to vitamin A deficiency globally. CONCLUSIONS: The world
      community should strive to find food-based system approaches to eliminating
      vitamin A deficiency. Modifying agricultural systems in ways that will not only
      maximizing food production, but also insure nutritional adequacy of vitamin A is
      a desirable goal for many developing countries.

PMID- 9598791
TI  - Food systems for improved health: linking agricultural production and human
      nutrition.
AB  - OBJECTIVES: Link traditional agricultural production disciplines to the food
      sciences and the various disciplines concerned with human nutrition and health in
      order to find sustainable solutions to malnutrition. DESIGN: Develop a new
      integrated program area within a university by forging explicit linkages within a
      wide array of disciplines concerned with food systems and human health. SETTING:
      The College of Agriculture and Life Sciences, the College of Human Ecology, the
      Division of Nutrition, and the Cornell International Institute for Food,
      Agriculture, and Development at Cornell University, Ithaca, New York, USA.
      INTERVENTIONS: Use food-based, system approaches to meet human nutrition goals.
      Current focus is on the provision of micronutrients (especially iron, vitamin A
      and iodine) for people globally. RESULTS: A new program area 'Food Systems for
      Health' has been developed at Cornell University. The program fosters effective
      interdisciplinary research, teaching and extension activities directed towards
      sustainable improvements in human nutrition and health. CONCLUSIONS: The old
      paradigms of agriculture, human nutrition, and public health must be shifted from
      current linear approaches to integrated and interactive approaches if effective
      long-term, food-based solutions to micronutrient malnutrition are to be found.

PMID- 9598793
TI  - Identification and production of local carotene-rich foods to combat vitamin A
      malnutrition.
AB  - OBJECTIVES: To address, with respect to improvement of human vitamin A status by
      dietary approaches, the three theoretical postulates that: 1) the most practical
      and economical manner to increase the amount of dietary vitamin A available to
      low-income persons in low-income nations is through plant sources of provitamin A
      carotenoids; 2) there will be constraints and limitation to the efficiency of a
      given intervention approach related to behavioural, cultural, biological and
      botanical considerations; and 3) the nature of these constraints and limitations
      must be understood, and then overcome where possible, to maximize the impact of
      such interventions on the vitamin A status of developing country populations.
      CONCLUSIONS: We review how local plant sources of provitamin A that would be
      acceptable for the at-risk populations and outline six settings and scenarios for
      the processing of carotene-rich foods: 1) cooking for hygiene; 2) long-term
      preservation; 3) compacting to reduce volume; 4) formulation for specific
      consumers; 5) improving bioavailability and bioconversion; and 6) to increase
      'value added' in commerce. We describe our experiences in Guatemala (with sweet
      potato flakes), and those of others in the Caribbean, the African Sahel, and East
      Africa (with solar-drying for preservation of a variety of plants), and in Sri
      Lanka (with leaf concentrates) in promoting increased carotene-rich food intake,
      and the lessons learned from their evaluations. This overall approach to
      combatting endemic hypovitaminosis A in developing countries is evaluated within
      the constraints of: 1) the volumes of plant-based foods required to satisfy
      vitamin A requirements; and 2) the controversy over the true bioconversion
      efficiency of provitamin A from plant sources into the biologically-available
      active vitamin.

PMID- 9598794
TI  - FISH identifies inv(16)(p13q22) masked by translocations in three cases of acute
      myeloid leukemia.
AB  - The inv(16)(p13q22) masked by different translocations was detected by
      fluorescence in situ hybridization (FISH) and confirmed by molecular analysis in
      three adult patients presenting with acute myeloid leukemia (AML)-M2 (cases 1 and
      3) and M4Eo (case 2). Cytogenetic analysis revealed 47,XX,t(9;16)(p23;p13),+22
      (case 1); 46,XX,t(1;16)(p32;p13) (case 2); and 46,XY,?del(16)(q22) (case 3).
      Using a panel of probes for chromosomes 1, 9, 16, and 20 as well as probes to
      detect inv(16), i.e., two cosmid contigs hybridizing proximally and distally to
      the 16p13 breakpoint, FISH demonstrated inv(16) involving the derivative 16 as
      well as reciprocal translocations between 16q22-qter and 9p24 (case 1), 1p32
      (case 2), and 20q13 (case 3). In addition, a small interstitial del(16)(p13p13)
      proximal to the MYH11 breakpoint was detected in case 1. Reverse transcriptase
      polymerase chain reaction (RT-PCR) and Southern blot analysis showed a CBFB-MYH11
      fusion transcript and MYH11 rearrangement, respectively, in all three cases. We
      conclude that: 1) inv(16) can be masked by other structural abnormalities
      involving chromosome 16; 2) some of the so-called variant translocations not
      explored at the molecular level may in fact represent a masked inv(16); and 3)
      FISH, RT-PCR, and Southern blot analyses are reliable tools to detect masked
      inv(16) and should be applied in all AML cases with structural changes of
      chromosome 16.

PMID- 9598795
TI  - Amplification and expression of the HMGIC gene in a benign endometrial polyp.
AB  - In a totally benign endometrial polyp, double minute chromosomes were shown to
      contain an amplified and apparently nonrearranged HMGIC gene, expressed in the
      tumor cells, suggesting amplification of HMGIC through double minute chromosome
      formation as another hitherto unreported mechanism associated with the
      development of some mesenchymal tumors.

PMID- 9598796
TI  - The t(3;12)(q27;q14-q15) with underlying HMGIC-LPP fusion is not determining an
      adipocytic phenotype.
AB  - The HMGIC gene, located in chromosome band 12q15, is rearranged in many different
      benign human tumors, often resulting in its fusion to ectopic sequences from
      other genes. The t(3;12)(q27;q14-q15) fuses HMGIC with the LPP gene and has so
      far been described exclusively in lipomas. Thus, it can be hypothesized that this
      particular gene fusion determines the adipocytic differentiation. We studied five
      pulmonary chondroid hamartomas all showing a t(3;12)(q27;q14-q15) that apparently
      was identical to the one observed in lipomas. By fluorescence in situ
      hybridization we found that both HMGIC and LPP are disrupted by this
      translocation. By RT-PCR the existence of a HMGIC/LPP fusion gene was confirmed.
      These results show that the fusion is not specific for lipomas. We favor the
      hypothesis that it is an ectopic sequence fused to HMGIC that is responsible for
      a cell shift to an embryogenic stage. Following this hypothesis the phenotype of
      the tumor may be induced by extracellular signal transduction.

PMID- 9598797
TI  - Molecular cytogenetic analysis of consistent abnormalities at 8q12-q22 in breast
      cancer.
AB  - Studies using comparative genomic hybridization (CGH) indicate that portions of
      chromosome arm 8q from 8q12 to 8qter are present at an increased relative copy
      number in a broad range of solid tumors. In this study we define an approximately
      1 Mb wide region that appears to be frequently abnormal in copy number or
      structure in breast cancer cell lines and primary tumors. This was accomplished
      by fluorescence in situ hybridization (FISH) with yeast artificial chromosomes
      (YACs) mapped to 8q2-q22. Eleven breast cancer cell lines and ten primary tumors
      were analyzed. A minimal region of rearrangement was localized to the CEPH-YAC
      928F9 in three breast cancer cell lines with unbalanced translocation breakpoints
      mapping in this region. Unbalanced translocations also were detected in two
      primary tumors mapping between CEPH-YAC clones 890C4 and 936B3, flanking 928F9.
      An increased copy number in the minimal region was detected in nine cell lines
      and in multiple primary tumors. This suggests the possibility that a single gene
      mapping to 928F9 is involved in breast cancer development or progression and may
      be deregulated by copy number increases in some tumors and by translocation in
      others. Four expressed sequence tags were mapped to YAC 928F9 and analyzed for
      rearrangements by Southern analysis and for abnormal expression by Northern
      analysis.

PMID- 9598798
TI  - Chromosomal abnormalities in nodal and extranodal CD30+ anaplastic large cell
      lymphomas: infrequent detection of the t(2;5) in extranodal lymphomas.
AB  - To determine the significance of the t(2;5)(p23;q35) translocation in nodal and
      extranodal anaplastic large cell lymphoma (ALCL), we performed cytogenetic,
      molecular genetic, and immunohistochemical analyses of tumor tissues from 11
      patients with CD30+ ALCL. Three of five patients with nodal ALCL had additional
      infiltration of the skin. Six patients had extranodal ALCL, two had primary
      intestinal ALCL, three had a primary cutaneous ALCL, and one had osseous ALCL.
      Cytogenetic investigation detected the t(2;5) in all patients with nodal ALCL but
      not extranodal ALCL. Tumor cells in t(2;5)+ lesions also stained
      immunohistochemically for p80NPM/ALK, whereas no staining for p80NPM/ALK was
      detected in extranodal ALCL. Two extranodal lesions had NPM/ALK fusion
      transcripts detected by nested reverse transcriptase-polymerase chain reaction.
      Fluorescence in situ hybridization analysis of these two lymphomas showed in one
      case a significant number (4%) of cells with a split hybridization signal,
      indicative of disruption of the NPM gene. Additional recurrent breakpoints
      observed in extranodal ALCL were 1p36, 6p25, and 8q24. Loss of genetic material
      occurred at 6q in one extranodal ALCL. Our results suggest that the t(2;5) more
      frequently plays a pathogenetic role in primary nodal than in extranodal ALCL and
      that this translocation may not be the primary event in some CD30+ ALCL.

PMID- 9598799
TI  - Cytogenetic comparison of primary tumors and lymph node metastases in breast
      cancer patients.
AB  - Chromosome banding analysis of primary tumors and axillary lymph node metastases
      from 10 breast cancer patients revealed abnormal karyotypes in all samples with
      cytogenetic similarities between the primary tumor and the metastasis in all
      informative pairs. Although karyotypically unrelated clones were also found in
      the lymph node samples, they were less numerous than in the primary tumors,
      indicating that there was more genetic heterogeneity among the neoplastic cells
      in the primary than in the secondary tumors. On the other hand, some of the
      clones had become more complex in the metastases as a result of clonal evolution,
      and by and large these metastatic breast cancer cases had more karyotypic
      anomalies than do unselected primary breast carcinomas. Among the aberrations
      occurring more frequently, and that consequently may predispose to disease
      spread, were losses of chromosomes 17 and 22 and homogeneously staining regions,
      a cytogenetic sign of gene amplification.

PMID- 9598800
TI  - Deletion mapping of endocrine tumors localizes a second tumor suppressor gene on
      chromosome band 11q13.
AB  - Multiple endocrine neoplasia type 1 syndrome (MEN1, MIM 131100), an autosomal
      dominant disease, is characterized by parathyroid hyperplasia, pancreatic
      endocrine tumors, and pituitary adenomas. These tumors also occur sporadically.
      Both the familial (MEN1) and the sporadic tumors reveal loss of heterozygosity
      (LOH) for chromosome band 11q13 sequences. Based on prior linkage and LOH
      analyses, the MEN1 gene was localized between PYGM and D11S460. Recently, the
      MEN1 gene (menin) has been cloned from sequences 30-kb distal to PYGM. We
      performed deletion mapping on 25 endocrine tumors (5 MEN1 and 20 sporadic) by
      using 21 polymorphic markers on chromosome band 11q13. Of these, two (137C7A,
      137C7B) were derived from PYGM-containing BAC (bacterial artificial chromosome
      137C7) sequences, one from INT2-containing cosmid sequences and the marker
      D11S4748, a (CA)20 repeat marker that was developed by us. The LOH analysis shows
      that the markers close to the MEN1 (menin) gene were not deleted in three of the
      tumors. These tumors, however, showed LOH for distal markers. Thus, the data
      suggest the existence of a second tumor suppressor gene on chromosome band 11q13.

PMID- 9598801
TI  - Novel mutations in the polyadenine tract of the transforming growth factor beta
      type II receptor gene are found in a subpopulation of human pancreatic
      adenocarcinomas.
AB  - In this study, we determined the incidence of microsatellite instability (MIN) in
      pancreatic adenocarcinoma and determined whether MIN might target, for mutations,
      the simple nucleotide repeats of the transforming growth factor beta type II
      receptor (TGFBR2) gene. Forty-eight surgically resected pancreatic tumor tissue
      samples and two normal pancreas tissue samples were analyzed in this study.
      Microsatellite analysis was performed for six loci in 14 of the 48 tumor
      specimens for which we had matching normal genomic DNA. Only four of the 14
      tumors (29%) were MIN-positive as determined by the presence of microsatellite
      variations in more than one locus. Interestingly, eight of the 14 specimens (57%)
      showed microsatellite variations or loss of heterozygosity at D18S34, suggesting
      that this locus may be a critical region of genetic instability in pancreatic
      tumorigenesis. Of the 48 tumors, only two (4%) showed mutations in the polyA
      region, one of the MIN-targeted sites of the TGFBR2 gene. DNA sequence analysis
      of these two specimens showed the presence of a two-base deletion in one tumor
      specimen and the other tumor specimen showed a base substitution in the polyA
      tract at codon 128 of the TGFBR2 gene. The fact that these mutations occurred in
      the polyA tract of some pancreatic tumors suggests that a subpopulation of these
      tumors may be susceptible to MIN-targeted mutations. The incidence of these
      mutations are low and similar to that reported for nonhereditary, sporadic colon
      cancers.

PMID- 9598802
TI  - Cytogenetic analysis shows that carcinosarcomas of the breast are of monoclonal
      origin.
AB  - Carcinosarcoma of the breast is a rare biphasic neoplasm composed of a
      carcinomatous component contiguous or admixed with a pleomorphic spindle cell
      component. The issues of the histogenesis and clonal composition of
      carcinosarcomas have long been debated. We present the first cytogenetic
      characterization of mammary carcinosarcomas by analysis of eight tumor samples
      from two patients with this disease. In the first case, the same karyotypically
      complex clone, as well as evidence of clonal evolution, was found in samples from
      three separate areas of the primary tumor. The analysis of one intramammary and
      one axillary lymph node metastasis from the same patient, both showing only the
      sarcomatous tumor component, also revealed the common complex stemline and one of
      the two sidelines found in the primary tumor. The carcinosarcoma of the second
      patient contained six complex but karyotypically related clones unevenly
      distributed among the three samples examined. From this case, cells belonging to
      the carcinomatous and sarcomatous tumor components were separated by differential
      sedimentation and culturing in specific growth media. Analysis of both fractions
      showed largely the same karyotype, although one of the subclones was restricted
      to the epithelial component. Our findings indicate that the epithelial and
      mesenchymal components of mammary carcinosarcomas are both part of the neoplastic
      parenchyma and that they have evolved from a single common stem cell, in
      agreement with the hypothesis that the tumors are of monoclonal origin.

PMID- 9598803
TI  - Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers.
AB  - The PTEN/MMAC1/TEP1 gene has been isolated as a tumor suppressor gene that is
      altered in several types of human tumors including brain, breast, and prostate
      cancers. In the present study, we report PTEN/MMAC1/TEP1 alterations in human
      lung cancers. Intragenic homozygous deletions were detected in 6 (40%) of 15
      small cell lung carcinoma (SCLC) cell lines and in 2 (8%) of 25 non-small cell
      lung carcinoma (NSCLC) cell lines. A nonsense mutation and a missense mutation
      were detected in 2 (8%) NSCLC cell lines. An intragenic homozygous deletion, a 1
      bp frameshift mutation, and a nonsense somatic mutation were also detected in
      three (6%) of 47 surgical specimens. All the lung tumors with PTEN/MMAC1/TEP1
      mutations were homozygous for the mutant alleles. These findings suggest that
      PTEN/MMAC1/TEP1 plays a role as a tumor suppressor gene in the genesis and/or
      progression of human lung cancer.

PMID- 9598805
TI  - The calendar and acute pancreatitis.
AB  - To find out whether a seasonal pattern exists for acute pancreatitis, the weekday
      and month of admission were retrospectively checked for 263 patients admitted to
      our hospital from 1987 to 1995 with their first attack of this disease. Etiology
      was biliary in 105 (40%), alcoholic in 84 (32%), unknown in 54 (21%), and
      presumed to be other in 20 (7%) patients. Forty-two (16%) patients had
      necrotizing acute pancreatitis. There was no significant correlation between
      admission and a specific month or weekday. Furthermore, there was no significant
      correlation between the etiology or onset of symptoms and a specific weekday. In
      contrast to other gastroenterological diseases such as peptic ulcer and
      inflammatory bowel disease, there is no seasonal or weekly pattern for acute
      pancreatitis.

PMID- 9598804
TI  - Virtually 100% of melanoma cell lines harbor alterations at the DNA level within
      CDKN2A, CDKN2B, or one of their downstream targets.
AB  - The cyclin-dependent kinase inhibitor 2A (CDKN2A), or p16INK4a, gene on 9p21 is
      important in the genesis of both familial and sporadic melanoma. Homozygous
      deletions and intragenic mutations of this gene have been identified in both
      melanoma cell lines and uncultured tumors, although the frequency of these
      alterations is higher in the cell lines. A proportion of melanoma cell lines and
      tumors without deletion/mutation of CDKN2A have also been determined to harbor
      transcriptionally inactive CDKN2A alleles or carry alterations in other
      components of the pathway through which p16INK4a acts on pRb to mediate cell
      cycle arrest. We sought to determine the frequency of these alternative events
      (in relationship to those that specifically inactivate CDKN2A) in a panel of 45
      melanoma cell lines. Surprisingly, at the DNA level alone, 96% (43/45) of
      melanoma cell lines examined were found to be deleted/mutated/methylated for
      CDKN2A (34/45), homozygously deleted for CDKN2A's neighbor and homolog CDKN2B
      (6/45), and/or mutated/amplified for CDK4 (5/45). In two of these 43 cases,
      homozygous deletions of CDKN2A were detected along with a CDK4 mutation or
      amplification of the cyclin D1 (CCND1) gene. The latter discoveries were made in
      two of three cell lines which harbored extremely large (3-6 Mb) homozygous
      deletions on 9p21; all other homozygous deletions in similarly affected cell
      lines (N = 23) were confined to a region immediately surrounding the
      CDKN2A/CDKN2B loci. These results suggest that (1) only melanoma cells with
      alterations in this pathway can be propagated in culture, and (2) the homozygous
      deletions on 9p21 in the cell lines, which are also mutated/amplified for CDK4 or
      CCND1, could serve to target tumor suppressor genes other than CDKN2A.

PMID- 9598806
TI  - Expression of transforming growth factor beta1 (TGFbeta1) and its receptors in
      pancreatic duct cell carcinoma and in chronic pancreatitis.
AB  - Transforming growth factor beta1 (TGF beta1) is a multifunctional factor that
      regulates many aspects of cellular functions such as epithelial cell growth and
      synthesis of extracellular matrices. TGFbeta transduces signaling through a
      heterodimeric complex of type I and type II TGFbeta receptors (TbetaRI and
      TbetaRII). Recently, it has been shown that enhanced expression of TGFbeta1 is
      associated with the progress of pancreatic duct cell carcinoma (PDC) and chronic
      pancreatitis (CP). In this study, the expression of TGFbeta1 and its receptors,
      TbetaRI and TbetaRII, is examined in 21 cases of PDC by immunohistochemistry
      using specific antibodies, and the results are compared with those for 13 cases
      of CP. In the epithelial cells of PDC and CP, there are no significant
      differences in the expression of TGFbeta1, TbetaRI, and TbetaRII. In contrast,
      stromal expression of this cytokine and its receptors tends to be stronger in PDC
      than in CP; especially, the expression of TbetaRII is significantly stronger in
      PDC (p < 0.05). These findings suggest that there are some pathological
      differences in the properties of stromal reactions between PDC and CP, although
      the morphologies of their stroma resemble each other.

PMID- 9598807
TI  - Quantification of human lithostathine S2-5 forms using the antibody to the N
      terminal peptide region.
AB  - Lithostathine S2-5 inhibits in vitro crystal growth of CaCO3. We developed an
      antibody against the peptide region responsible for inhibitory effect to
      determine whether lithostathine S2-5 levels are different in the pancreatic juice
      of patients with and without chronic pancreatitis. The antibody against the
      synthetic peptide of the N-terminal end of lithostathine S2-5 detected
      lithostathine S2-5 but not lithostathine S1 or lithostathine extracted from
      pancreatic calculi. Lithostathine S2-5 was detected in samples of pancreatic
      juice protein by immunoblotting using the specific antibody. The concentration of
      lithostathine S2-5 was compared between control and chronic pancreatitis groups.
      The mean concentrations of lithostathine S2-5 were significantly (p=0.002) lower
      in chronic pancreatitis, 16.3 microg/mg of total protein, than in the control,
      47.1 microg/mg of total protein. A decreased concentration of lithostathine S2-5
      seems to increase the risk of stone formation in the ducts during the course of
      chronic pancreatitis because of insufficient inhibition of CaCO3 crystal growth.

PMID- 9598808
TI  - Hydrogen breath test with glucose in exocrine pancreatic insufficiency.
AB  - The present study was designed to investigate the prevalence of bacterial
      overgrowth in patients with exocrine pancreatic insufficiency by using the
      hydrogen breath test with glucose. Thus, in 30 patients with exocrine pancreatic
      insufficiency (in 15 due to chronic pancreatitis and in 15 associated to primary
      immunodeficiency), established by quantifying trypsin output before and after
      stimulation with cerulein using a duodenal perfusion technique, a glucose test
      was performed by administering 50 g of glucose and quantifying H2 in the breath
      by gas chromatography. The glucose test was positive in six of 15 patients with
      chronic pancreatitis but in only one of 15 immunodeficient patients (p < 0.05).
      Age, sex, etiology, time of evolution, associated diabetes, pancreatic
      calcifications, duodenal pH, or duodenal trypsin output did not differ between
      patients with and those without bacterial overgrowth. Previous gastroduodenal
      surgery was more common in chronic pancreatitis patients with overgrowth (six of
      six vs. four of nine; p < 0.05). Five patients with a positive glucose test were
      treated with antibiotics for 2 weeks and became negative in two of them. These
      results suggest that a positive glucose test indicating overgrowth is relatively
      common in exocrine pancreatic insufficiency due to chronic pancreatic, especially
      in patients with previous gastroduodenal surgery.

PMID- 9598809
TI  - Prolyl hydroxylase and tissue inhibitor of metalloproteinase in pure pancreatic
      juice in patients with chronic pancreatitis.
AB  - Prolyl hydroxylase is a key enzyme in collagen synthesis, and tissue inhibitor of
      metalloproteinase (TIMP) is known to suppress collagenolytic enzymes. To see
      whether the levels of these two enzymes in serum and human pure pancreatic juice
      (PPJ) are good indicators of pancreatic fibrosis in chronic pancreatitis (CP), we
      examined 15 controls, 14 alcoholics without evident pancreatic diseases (7
      current drinkers and 7 former drinkers), and 19 patients with CP. Levels of the
      two enzymes were determined by a sandwich enzyme immunoassay method. TIMP-1
      levels in PPJ were significantly higher in patients with CP than in controls and
      alcoholics, with overlap in only a few exceptional patients. A significant
      inverse correlation between TIMP-1 and bicarbonate output in PPJ was observed.
      Prolyl hydroxylase levels in PPJ, in contrast, were significantly higher in
      current drinkers than in patients with CP, controls, and former drinkers, with
      overlap in only a few exceptional patients with relapsing CP. Identical results
      were obtained even when the enzyme levels were expressed as nanograms per
      milligram of protein. Serum levels of prolyl hydroxylase and TIMP-1 showed no
      significant differences among controls, current alcoholics, former alcoholics,
      and patients with CP. These results indicate that the raised level of TIMP-1 in
      PPJ, unlike that of prolyl hydroxylase, is a good indicator of pancreatic
      fibrosis in CP.

PMID- 9598810
TI  - Enhanced Krev-1 expression inhibits the growth of pancreatic adenocarcinoma
      cells.
AB  - Pancreatic ductal adenocarcinoma is characterized by a high rate of activating
      mutations involving codon 12 of the K-ras protooncogene. As a means of ras
      targeted intervention, the effects of enhanced Krev-1 gene expression on the
      growth and tumorigenicity of the hamster pancreatic adenocarcinoma cell line PC-1
      were evaluated. Overexpression of the Krev-1 gene product resulted in morphologic
      reversion to a less transformed phenotype, as well as retarded growth kinetics
      and diminished potential for anchorage-independent growth. Among six transfected
      cell lines, the magnitude of these changes correlated with the degree of Krev-1
      overexpression as assessed by Western blot. When PC-1 cells overexpressing high
      levels of the Krev-1 gene product were assessed for tumorigenicity in syngeneic
      animals, an increased latency to tumor growth and a decreased tumor size were
      noted. The results confirm that overexpression of the Krev-1 gene may provide a
      useful strategy for ras-targeted intervention in this disease.

PMID- 9598811
TI  - Jun and MAP kinases are activated by cholecystokinin in the pancreatic carcinoma
      cell line KP-1N.
AB  - Growth of the human pancreatic carcinoma cell line KP-1N was stimulated with
      cholecystokinin (CCK)-8. A 40% increase in cell numbers was observed in the
      presence of 10(-10) MCCK-8 and this increase was inhibited by the addition of 25
      microM CCK-A receptor antagonist (CR1505). The binding affinity of CCK-8 to KP-1N
      cells was 21-fold higher than that of gastrin 17-I. No significant increase in
      intracellular Ca2+ concentration was found upon stimulation with CCK-8.
      Components of signal transduction pathways that were activated in KP-1N cells
      after stimulation with CCK-8 were studied. CCK-8 stimulated tyrosine
      phosphorylation of a mitogen-activated protein kinase (MAPK) of approximately 42
      kDa (p42map). c-Jun amino-terminal kinases (JNKs) of 46 kDa (p46jnk) and 55 kDa
      (p55jnk) were also activated by CCK-8 and increased the phosphorylation of c-Jun.
      CCK-8 at 10(-7) M induced 1.5-fold increases in the phosphorylation of MAPK and
      of c-Jun by JNKs, respectively. These results suggest that cell proliferation
      stimulated with CCK-8 in KP-1N cells may be mediated by signal transduction
      cascades leading to activation of JNKs and MAPKs.

PMID- 9598812
TI  - Proliferative effect of phospholipase A2 on rat periacinar fibroblastoid cells of
      the pancreas.
AB  - We have shown previously that rat pancreatic periacinar fibroblastoid cells
      (PFCs) can be cultured from isolated pancreatic acini. In the present study,
      immunocytochemical examination of the PFC extracellular matrix was performed
      using antibodies against prolyl hydroxylase alpha and beta subunits, types I,
      III, and IV collagen, fibronectin, and laminin. The PFC content of alpha-smooth
      muscle actin and platelet-derived growth factor (PDGF) receptor were studied by
      immunoblotting. We demonstrated that PFCs synthesized extracellular matrix and
      expressed alpha-smooth muscle actin and PDGF receptors. These results suggested
      that PFCs resemble myofibroblasts and may play a critical role in pancreatic
      fibrosis. Conversely, pancreatic-type phospholipase A2 (P-PLA2), one of the
      pancreatic digestive enzymes, has been shown to induce DNA synthesis of Swiss 3T3
      fibroblasts. To determine whether this enzyme is involved in pancreatic fibrosis,
      we studied P-PLA2's proliferative and chemotactic effects on PFCs as well as its
      digestive activity. The proliferative and chemotactic effects were investigated
      using 3H-thymidine incorporation and a chemotactic assay, respectively. P-PLA2
      had both proliferative and chemotactic effects. P-PLA2 is considered a growth
      factor for PFCs and is implicated in pancreatic fibrosis.

PMID- 9598813
TI  - Effect of 3-O-methylglucose on insulin secretion in the perfused dog and rat
      pancreas.
AB  - We recently reported that the nonmetabolizable glucose analogue, 3-O
      methylglucose, stimulates somatostatin secretion in the perfused dog pancreas. In
      this study, we report that 3-O-methylglucose also stimulates insulin secretion in
      the dog pancreas. The effect was present at 5.5 mM glucose (p < 0.001) but not at
      O or 2.7 mM glucose. The inhibitor of glucose metabolism, mannoheptulose, blocked
      the insulinotropic action of 3-O-methylglucose. In contrast, 3-O-methylglucose
      had no effect on insulin secretion in the perfused rat pancreas. We conclude that
      3-O-methylglucose stimulates insulin secretion in the dog and that the effect
      requires the presence of stimulatory concentrations of D-glucose.

PMID- 9598814
TI  - Profile and differential expression of protein tyrosine phosphatases in mouse
      pancreatic islet tumor cell lines.
AB  - Protein tyrosine phosphatases (PTPs) play important roles in cell growth and
      differentiation of normal and tumor cells. In this study, we analyzed the PTP
      profile in two pancreatic islet tumor cell lines. Transcripts were isolated from
      alphaTC-1 (glucagon-secreting) and betaTC-1 (insulin-secreting) cell lines for
      templates. A pair of degenerative primers, based on the conserved regions of
      known PTPs, was used to amplify the transcripts by polymerase chain reaction. A
      total of 1,620 clones was examined by restriction enzyme analysis and cDNA
      sequencing. Twenty-one PTPs were identified, including nine cytosolic PTPs
      (TcPTP, P19PTP, PTP1B, PTPMEG, PTP1C, SYP, PTPH1, PTPL1, and PTPD1), nine
      transmembrane PTPs (PTPdelta, PTPgamma, PTPkappa, DEP-1, IA-2, LAR, PTPalpha,
      PTPNE3, and PTPepsilon), and three new PTPs--PTPmu-like PTPkappa-like, and IA
      2beta. An RNase protection assay demonstrated that some of these PTPs were
      expressed predominantly in glucagonoma (i.e., PTPdelta and IA-2) and others in
      insulinoma (i.e., PTP1C, PTPkappa, and PTPNE3) cells. In this report, we present
      the first profile of PTPs in alpha and beta tumor cell lines.

PMID- 9598815
TI  - Up-regulation of cytochrome P450 1A2, 2C9, and 2E1 in chronic pancreatitis.
AB  - The oxidative metabolism of xenobiotics is effected mainly by cytochrome P450
      enzymes (CYP), which are expressed as a family of genetically related enzymes
      primarily in hepatocytes. The pancreas is among the extrahepatic tissues
      expressing CYP, and it has been suggested that intermediates generated by them
      might be of pathogenetic significance for diseases of the pancreas such as
      chronic pancreatitis. We studied 10 surgical resection specimens by
      immunohistochemistry with polyclonal antibodies against recombinant human CYP
      1A1, 1A2, 2C9, 2E1, and 3A and used tissues from 11 normal pancreata as controls.
      In addition, we assayed microsomal preparations for their capacity to metabolize
      verapamil. In normal pancreata weak to moderate expression of all enzymes was
      demonstrated immunohistochemically in up to 50% of duct epithelia, acinar cells,
      and islet cells. In contrast, in chronic pancreatitis an up-regulation was
      observed, with immunohistochemical positivity in some cases in up to 100% of duct
      epithelia and acinar cells. The oxidative capacity of microsomal preparations
      from chronic pancreatitis was higher than that of preparations obtained from
      control tissues; compared to liver microsomes, however, it was low. The up
      regulation of CYP may have pathogenetic significance for chronic pancreatitis.
      Yet considering the pancreas' capacity for conjugation reactions, conceivably low
      levels of reactive intermediates could effectively undergo inactivation.

PMID- 9598816
TI  - Effect of the lectins wheat germ agglutinin (WGA) and Ulex europaeus agglutinin
      (UEA-I) on the alpha-amylase secretion of rat pancreas in vitro and in vivo.
AB  - Lectins are able to bind to cholecystokinin (CCK) receptors and other
      glycosylated membrane proteins. The lectins wheat germ agglutinin (WGA) and Ulex
      europaeus agglutinin (UEA-I) are used for affinity chromatography to isolate the
      highly glycosylated CCK-A receptor of pancreatic acinar cells. According to the
      working hypothesis that lectin binding to the CCK receptor should alter the
      ligand-receptor interaction, the effect of WGA and UEA-I on CCK-8-induced enzyme
      secretion was studied on isolated rat pancreatic acini in vitro. In vitro both
      lectins showed a dosage-dependent inhibition of CCK-8-induced alpha-amylase
      secretion of acini over 60 min. WGA showed a strong inhibitory effect on amylase
      secretion, approximately 40%, in vitro. UEA-I caused a smaller, but significant
      decrease, approximately 20%, in enzyme secretion of isolated acini. Additionally,
      both lectins inhibited cerulein/secretin- or cerulein-induced pancreatic
      secretion of rats in vivo, but not after secretin alone. The results are
      discussed with respect to a possible influence of both lectins on the interaction
      of CCK or cerulein with the CCK-A receptor.

PMID- 9598817
TI  - Lipopolysaccharide-induced desensitization to pancreatic edema formation in rat
      cerulein pancreatitis.
AB  - Previously we reported that prior administration of lipopolysaccharide (LPS)
      mitigates subsequently produced cerulein (Cn) pancreatitis. To clarify the
      mechanism further, the pathological features of Cn pancreatitis were examined in
      detail after treating rats with very low doses of LPS. LPS pretreatment reduced
      the formation of pancreatic edema during Cn pancreatitis in a dose- and time
      dependent manner. In contrast, the elevation of serum amylase and the
      histological findings, including acinar cell vacuolization and infiltration of
      inflammatory cells, were not affected. The lowest dose of LPS, 500 ng/kg, was
      sufficient to inhibit pancreatic edema formation completely. LPS at a dose of 5
      microg/kg was fully effective when it was given from 30 min to 12 h before the
      induction of pancreatitis. Pretreatment with tumor necrosis factor-alpha (TNF
      alpha) inhibited the pancreatic edema in a manner similar to that of LPS.
      Moreover, the inhibitory effect of LPS was partially attenuated by the
      administration of anti-TNF-alpha antibody before the injection of LPS.
      Actinomycin D (0.5 mg/kg) abolished the effect of LPS, whereas cycloheximide (0.5
      mg/kg) given alone reduced pancreatic edema formation during pancreatitis. From
      these results, it was concluded that very low doses of LPS can induce, partially
      via TNF-alpha, a state refractory to pancreatic edema formation during Cn
      pancreatitis, and this phenomenon seems to be regulated at the transcriptional
      level.

PMID- 9598818
TI  - Calcitonin-secreting tumors of the pancreas: about six cases.
AB  - Calcitonin release has rarely been reported in patients (pts) with neuroendocrine
      pancreatic tumors (NPT). The aim of this study was to describe the
      characteristics of calcitonin-secreting tumors (CST) of the pancreas. Serum
      calcitonin determination was part of the prospective evaluation of 66 pts with
      NPT referred to our institution over a 3-year period. Six pts (9%) had elevated
      calcitonin levels [at least twice the limit of the normal value (N)]. Abdominal
      ultrasonography, computed tomography scan, and endoscopic ultrasound were
      performed to identify the primary tumor(s) and metastases. Immunostaining using
      anticalcitonin and other antibodies was performed on the surgical resection
      specimen (four pts) or biopsy of liver metastases (two pts). Three of the six pts
      (four males, two females; median age, 51.5 years) had diarrhea. Serum calcitonin
      levels (median, range) were 17.5 N (6N-40N). Slight elevations in serum
      somatostatin (1.2N-2.3N) were associated in three pts. Pancreatic tumors were
      single in five of six pts and evenly distributed in the head and in the tail.
      Five pts had metastases, mainly in the liver. Multiple endocrine neoplasia type I
      was present in one pt. Immunostaining using calcitonin and somatostatin
      antibodies was positive in four pts each, respectively, and areas that were
      positive for one peptide were negative for the other. Diarrhea disappeared in the
      two pts who responded to treatment of the tumor(s). Three of the four pts with
      liver metastases died from tumor progression after 2, 10, and 24 months,
      respectively. CST of the pancreas are often malignant and can be considered as
      functional in half of the cases, irrespective of the serum calcitonin levels.
      Somatostatin secretion is often associated. Although rare, calcitonin secretion
      should be investigated in NPT pts presenting with diarrhea that cannot be
      explained by an increase in other hormone levels or in patients with
      nonfunctioning NPT.

PMID- 9598819
TI  - Subcutaneous manifestations of severe acute pancreatitis.
AB  - Subcutaneous manifestations of severe acute pancreatitis (Grey Turner's sign,
      Cullen's sign, and disseminated fat necrosis) are often discussed but seldom
      observed. Grey Turner's sign and Cullen's sign develop in <3% of patients with
      acute pancreatitis; subcutaneous fat necrosis occurs even less frequently. Few
      younger physicians have ever seen representative cases. Only recently have
      studies begun to clarify the development of these clinical signs. Grey Turner's
      sign is produced by the spread of hemorrhagic fluid from the posterior pararenal
      space to the lateral edge of the quadratus lumborum muscle and, subsequently, to
      the subcutaneous tissues via a defect in the fascia of the flank. Cullen's sign
      arises from the diffusion of retroperitoneal blood into the falciform ligament
      and, subsequently, to the subcutaneous umbilical tissues via the connective
      tissue covering of the round ligament complex. In contrast to the ecchymotic
      signs, our review of the existing literature concerning the development of
      subcutaneous fat necrosis in patients with acute pancreatitis did not reveal a
      definitive pathogenesis. Multiple factors seem to be involved in the production
      of subcutaneous fat necrosis, and a simple cause-and-effect relationship of
      circulating lipolytic enzymes seems unlikely.

PMID- 9598820
TI  - Acetaminophen-codeine combination induced acute pancreatitis.

PMID- 9598822
TI  - Evaluation of phospholipase A2 measurement for early prediction of the severity
      of acute pancreatitis.

PMID- 9598821
TI  - Interleukin-6 and Phospholipase A2 isoenzymes during acute pancreatitis.

PMID- 9598823
TI  - Concurrent acute hepatitis and pancreatitis associated with hepatitis B virus:
      case report.

PMID- 9598824
TI  - Laminar shear stress: mechanisms by which endothelial cells transduce an
      atheroprotective force.
AB  - Mechanical forces are important modulators of cellular function in many tissues
      and are particularly important in the cardiovascular system. The endothelium, by
      virtue of its unique location in the vessel wall, responds rapidly and
      sensitively to the mechanical conditions created by blood flow and the cardiac
      cycle. In this study, we examine data which suggest that steady laminar shear
      stress stimulates cellular responses that are essential for endothelial cell
      function and are atheroprotective. We explore the ability of shear stress to
      modulate atherogenesis via its effects on endothelial-mediated alterations in
      coagulation, leukocyte and monocyte migration, smooth muscle growth, lipoprotein
      uptake and metabolism, and endothelial cell survival. We also propose a model of
      signal transduction for the endothelial cell response to shear stress including
      possible mechanotransducers (integrins, caveolae, ion channels, and G proteins),
      intermediate signaling molecules (c-Src, ras, Raf, protein kinase C) and the
      mitogen activated protein kinases (ERK1/2, JNK, p38, BMK-1), and effector
      molecules (nitric oxide). The endothelial cell response to shear stress may also
      provide a mechanism by which risk factors such as hypertension, diabetes,
      hypercholesterolemia, and sedentary lifestyle act to promote atherosclerosis.

PMID- 9598825
TI  - Influence of oscillatory and unidirectional flow environments on the expression
      of endothelin and nitric oxide synthase in cultured endothelial cells.
AB  - In vivo, endothelial cells (ECs) are subjected to a complex mechanical
      environment composed of shear stress, pressure, and circumferential stretch. The
      aim of this study was to subject bovine aortic ECs to a pulsatile pressure
      oscillating from 70 to 130 mm Hg (mean of 100 mm Hg) in combination with
      pulsatile shear stresses from 0.1 to 6 dyne/cm2 (1 dyne/cm2=0.1 N/m2) with or
      without a cyclic circumferential stretch of 4% for 1, 4, and 24 hours. The effect
      of highly reversing oscillatory shear stress (range -3 to +3 dyne/cm2, mean of
      0.3 dyne/cm2) typical of regions prone to the development of atherosclerotic
      plaques was also studied at 4 and 24 hours. Endothelin-1 (ET-1) and endothelial
      constitutive nitric oxide synthase (ecNOS) mRNA expression was time and
      mechanical force dependent. ET-1 mRNA was maximal at 4 hours and decreased to
      less than static culture expression at 24 hours, whereas ecNOS mRNA increased
      over time. Pressure combined with low shear stress upregulated ET-1 and ecNOS
      mRNA compared with static control. Additional increase in expression for both
      genes was observed under a combination of higher shear stress and pressure. A
      cyclic circumferential stretch of 4% did not induce a further increase in ET-1
      and ecNOS mRNA at either low or high shear stress. Oscillatory shear stress with
      pressure induced a higher expression of ET-1 mRNA but lower expression of ecNOS
      mRNA compared with unidirectional shear stress and pressure. We have shown that
      the combination of pressure and oscillatory shear stress can downregulate ecNOS
      levels, as well as upregulate transient expression of ET-1, compared with
      unidirectional shear stress. These results provide a new insight into the exact
      role of mechanical forces in endothelial dysfunction in regions prone to the
      development of atherosclerosis.

PMID- 9598826
TI  - Binding of human urokinase-type plasminogen activator to its receptor: residues
      involved in species specificity and binding.
AB  - Urokinase-type plasminogen activator (UPA), particularly when bound to its
      receptor (UPAR), is thought to play a major role in local proteolytic processes,
      thus facilitating cell migration as may occur during angiogenesis, neointima and
      atherosclerotic plaque formation, and tumor cell invasion. To facilitate
      understanding of the need and function of the UPA/UPAR interaction in cell
      migration and vascular remodeling, we changed several amino acid residues in UPA
      so as to interfere with its interaction with its receptor. The receptor-binding
      domain of UPA has been localized to a region in the growth factor domain between
      residues 20 and 32. Since the binding of UPA to UPAR appears to be species
      specific, we used the differences in amino acid sequences in the growth factor
      domain of UPA between various species to construct a human UPA variant that does
      not bind to the human UPAR. We substituted Asn22 for its mouse equivalent Tyr by
      site-directed mutagenesis. This mutant UPA had similar plasminogen activator
      characteristics as wild-type UPA, including its specific activity and interaction
      with plasminogen activator inhibitor-1. However, no UPA/UPAR complexes could be
      observed in cross-linking experiments using DFP-treated 125I-labeled mutant UPA
      and lysates of various cells, including U937 histiocytic lymphoma cells, phorbol
      myristate acetate-treated human ECs, and mouse LB6 cells transfected with human
      UPAR cDNA. In direct binding experiments, DFP-treated 125I-labeled mutant UPA
      could not bind to phorbol myristate acetate-treated ECs, whereas wild-type UPA
      did bind. Furthermore, a 25-fold excess of wild-type UPA completely prevented the
      binding of DFP-treated 125I-labeled wild-type UPA to the human receptor on
      transfected LB6 cells, whereas an equal amount of mutant UPA had only a very
      small effect. In ligand blotting assays, very weak binding of mutant UPA to human
      UPAR could be observed. Changing Asn22 into the other amino acid residues alanine
      or glutamine had no effect on binding to UPAR on human ECs. The functional
      integrity of the growth factor domain in the non-receptor binding Asn22Tyr mutant
      is suggested by the fact that binding of this mutant to a murine UPAR can be
      restored after additional mutations in the growth factor domain,
      Asn27,His29,Trp30 to Arg27,Arg29,Arg30. We conclude that Asn22 and
      Asn27,His29,Trp30 in human UPA are key determinants in the species-specific
      binding of the enzyme to its receptor and that changing Asn22 into Tyr results in
      a UPA mutant with strongly reduced binding to UPAR.

PMID- 9598827
TI  - The relation between de novo atherosclerosis remodeling and angioplasty-induced
      remodeling in an atherosclerotic Yucatan micropig model.
AB  - Geometric remodeling in de novo atherosclerosis and in restenosis after balloon
      angioplasty constitutes a change in total arterial circumference that, together
      with plaque growth or neointima formation, determines the lumen of the artery.
      The heterogeneous nature of arterial obstructions raises the question of whether
      early and late outcomes (restenosis) of angioplasty are affected by the degree
      and direction of de novo atherosclerotic remodeling. This study was designed to
      assess the relationship between atherosclerotic remodeling and the degree and
      mechanism of restenosis after balloon angioplasty. Atherosclerosis was induced in
      27 peripheral arteries of 18 Yucatan micropigs by a combination of denudation and
      atherogenic diet. Balloon angioplasty was performed, with serial intravascular
      ultrasound and quantitative angiography before and after intervention and at 42
      days' follow-up. We used the relative media-bounded area (MBA), defined as the
      MBA of the treated site divided by the MBA of the reference, before angioplasty
      as a measure of remodeling in de novo atherosclerosis and late MBA loss as a
      measure of remodeling after balloon angioplasty. Relative MBA before angioplasty
      was not correlated with angiographic and echographic acute gain after balloon
      angioplasty (r=.22, P=.28 and r=.14, P=.48) or with late lumen loss (r=-.05,
      P=.81 and r=.19, P=.33). No correlation was found between relative MBA and late
      MBA loss (r=.14 and P=.48). In the atherosclerotic Yucatan micropig, remodeling
      during de novo atherosclerosis has no relevance for acute gain and late lumen
      loss after balloon angioplasty. Both the direction and the extent of remodeling
      after balloon angioplasty are not related to the direction and extent of
      remodeling during de novo atherosclerosis.

PMID- 9598828
TI  - Localizing role of hemodynamics in atherosclerosis in several human
      vertebrobasilar junction geometries.
AB  - Atherosclerosis is a common finding in the vertebrobasilar junction and in the
      basilar artery. Several theories try to link the process of atherogenesis with
      the forces exerted by the flowing blood. An attractive relation has been found
      between the locations in vessels at which atherosclerotic plaques are often
      present and the locations in models where complicated flow patterns exist. Most
      of the studies provided data on bifurcations. Finding a similar relation in an
      arterial confluence would certainly add to the credibility of the (causal)
      relationship between hemodynamics and atherosclerosis. Further support can be
      provided if variations of the geometry result in changes of the location of the
      atherosclerotic lesions, corresponding to the changes of the flow force
      distribution. In our previous numerical and experimental work, the influence of
      geometric and hemodynamic parameters, such as asymmetrical inflow, confluence
      angle, and blunting of the apex, on the flow in vertebrobasilar junction models
      has been investigated in detail. Recirculation areas and distribution of the wall
      shear stress have been computed. In this anatomic study, the effect of modulation
      of these geometric and hemodynamic parameters on the flow pattern is compared
      with the size and location of plaques in human vertebrobasilar junctions and
      basilar arteries. In addition, a comparison is made between the preferential
      areas of atherosclerotic plaques in junctions and bifurcations to demonstrate the
      localizing role of hemodynamics in atherogenesis. The apex of the vertebrobasilar
      junction and the lateral walls of the basilar artery appeared to be prone to
      atherosclerosis. In 43 of 85 vertebrobasilar junctions, a plaque was found at the
      apex. Furthermore, the summed plaque thickness at both lateral walls differs
      significantly (paired t test, P=.03) from that at the walls facing the pons and
      the skull base. In contrast, several authors found that the lateral walls of the
      mother vessel and the apex in bifurcations are often spared. Modulation of the
      various parameters in the models changed the size of the regions with low wall
      shear stress and/or recirculation areas dramatically. A comparable effect was
      found in the occurrence of plaques in the human vertebrobasilar junction; eg, for
      an atherosclerotic plaque at the apex, a predicted probability larger than 0.5
      was computed for blunted apexes and for sharp-edged apexes with a confluence
      angle exceeding 90 degrees. Apparently, two geometric risk factors for an
      atherosclerotic plaque at the apex can be distinguished: a blunted apex and a
      large confluence angle.

PMID- 9598829
TI  - Vascular endothelial cell regulation of extracellular matrix collagen: role of
      nitric oxide.
AB  - Endothelium-derived products have been implicated in the regulation of vascular
      wall structure through their effects on extracellular matrix metabolism. The
      purpose of this study was to further understand the paracrine mechanisms
      underlying endothelial cell regulation of extracellular matrix metabolism by
      testing the hypothesis that endothelium-derived nitric oxide decreases the
      concentration of soluble collagens derived from vascular smooth muscle cells
      (VSMCs). Porcine coronary endothelium and VSMCs were grown under a coculture
      configuration to assess the paracrine effects of nitric oxide produced by the
      endothelium on VSMC collagen types I and III. Endogenous endothelial cell nitric
      oxide production was blocked with N(omega)-nitro-L-arginine methyl ester.
      Collagen type I and type III were quantitatively measured using an enzyme-linked
      immunosorbent assay method. The endothelium elicited a time-dependent increase in
      the concentration of soluble VSMC-derived collagen type I; in contrast, collagen
      type III was decreased. After inhibition of nitric oxide production, there was a
      marked increase in both collagen types I and III concentration. These results
      demonstrated that endothelium-derived nitric oxide differentially alters collagen
      subtypes produced by VSMCs. The data support the hypothesis that nitric oxide
      functions via a paracrine mechanism to decrease VSMC collagen types I and III
      concentration, a finding consistent with an integral role for the endothelium in
      modulating extracellular matrix metabolism.

PMID- 9598830
TI  - Soluble cell adhesion molecules in hypertriglyceridemia and potential
      significance on monocyte adhesion.
AB  - Hypertriglyceridemia may contribute to the development of atherosclerosis by
      increasing expression of cell adhesion molecules (CAMs). Although the cellular
      expression of CAMs is difficult to assess clinically, soluble forms of CAMs
      (sCAMs) are present in the circulation and may serve as markers for CAMs. In this
      study, we examined the association between sCAMs and other risk factors occurring
      with hypertriglyceridemia, the effect of triglyceride reduction on sCAM levels,
      and the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte
      adhesion in vitro. Compared with normal control subjects (n=20), patients with
      hypertriglyceridemia and low HDL (n=39) had significantly increased levels of
      soluble intercellular adhesion molecule-1 (sICAM-1) (316+/-28.8 versus 225+/-16.6
      ng/mL), sVCAM-1 (743+/-52.2 versus 522+/-43.6 ng/mL), and soluble E-selectin
      (83+/-5.9 versus 49+/-3.6 ng/mL). ANCOVA showed that the higher sCAM levels in
      patients occurred independently of diabetes mellitus and other risk factors. In
      27 patients who received purified n-3 fatty acid (Omacor) 4 g/d for > or =7
      months, triglyceride level was reduced by 47+/-4.6%, sICAM-1 level was reduced by
      9+/-3.4% (P=.02), and soluble E-selectin level was reduced by 16+/-3.2%
      (P<.0001), with the greatest reduction in diabetic patients. These results
      support previous in vitro data showing that disorders in triglyceride and HDL
      metabolism influence CAM expression and treatment with fish oils may alter
      vascular cell activation. In a parallel-plate flow chamber, recombinant sVCAM-1
      at the concentration seen in patients significantly inhibited adhesion of
      monocytes to interleukin-1-stimulated cultured endothelial cells under conditions
      of flow by 27.5+/-7.2%. Thus, elevated sCAMs may negatively regulate monocyte
      adhesion.

PMID- 9598831
TI  - Effect of thyroid function on LDL oxidation.
AB  - In this study, the effect of different levels of thyroid hormone and metabolic
      activity on low density lipoprotein (LDL) oxidation was investigated. Thus, in 16
      patients with hyperthyroidism, 16 with hypothyroidism, and 16 age- and sex
      matched healthy normolipidemic control subjects, the native LDL content in lipid
      peroxides, vitamin E, beta-carotene, and lycopene, as well as the susceptibility
      of these particles to undergo lipid peroxidation, was assessed. Hyperthyroidism
      was associated with significantly higher lipid peroxidation, as characterized by
      a higher native LDL content in lipid peroxides, a lower lag phase, and a higher
      oxidation rate than in the other two groups. This elevated lipid peroxidation was
      associated with a lower LDL antioxidant concentration. Interestingly, hypothyroid
      patients showed an intermediate behavior. In fact, in hypothyroidism, LDL
      oxidation was significantly lower than in hyperthyroidism but higher than in the
      control group. Hypothyroidism was also characterized by the highest beta-carotene
      LDL content, whereas vitamin E was significantly lower than in control subjects.
      In hyperthyroidism but not in the other two groups, LDL oxidation was strongly
      influenced by free thyroxine blood content. In fact in this group, the native LDL
      lipid peroxide content and the lag phase were directly and indirectly,
      respectively, related to free thyroxine blood levels. On the contrary, in
      hypothyroidism LDL oxidation was strongly and significantly related to serum
      lipids. In conclusion, both hypothyroidism and hyperthyroidism are characterized
      by higher levels of LDL oxidation when compared with normolipidemic control
      subjects. In hyperthyroid patients, the increased lipid peroxidation was strictly
      related to free thyroxine levels, whereas in hypothyroidism it was strongly
      influenced by serum lipids.

PMID- 9598832
TI  - Esterified cholesterol accumulation induced by aggregated LDL uptake in human
      vascular smooth muscle cells is reduced by HMG-CoA reductase inhibitors.
AB  - Vascular smooth muscle cell (VSMC) proliferation is a key event in the
      development of atherosclerotic lesions. VSMCs synthesize extracellular matrix,
      where low density lipoproteins (LDLs) are trapped and become aggregated (agLDL).
      The objective of this study was to investigate the cholesterol uptake and
      accumulation triggered by agLDL in comparison with native LDL (nLDL) on
      unstimulated and platelet-derived growth factor-stimulated human aortic VSMCs and
      the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on these
      processes. Esterified cholesterol (EC) accumulation induced by agLDL in VSMCs was
      correlated with the degree of aggregation and concentration. The EC content of
      VSMCs treated with 100 microg/mL of agLDL (80% aggregated) increased
      approximately 70-fold over that in VSMCs incubated with the same concentration of
      nLDL. Whereas nLDL-derived EC was increased approximately twofold in platelet
      derived growth factor-stimulated VSMCs, there was no effect of platelet-derived
      growth factor (10(-9) mol/L) on the uptake of agLDL. The 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitor simvastatin (5 micromol/L) reduced
      EC accumulation derived from agLDL uptake by 58% and 35% in platelet-derived
      growth factor-stimulated and unstimulated VSMCs, respectively. This inhibition
      was overcome by geranylgeraniol (10 micromol/L) and partially by farnesol (10
      micromol/L). Fluorescence microscopy of the cellular internalization of agLDL
      labeled with the fluorochrome 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine demonstrated that simvastatin reduces EC accumulation
      derived from agLDL by inhibiting its endocytosis and that the effect is
      completely reversed by geranygeraniol. These results indicate that agLDLs are
      rapidly internalized by human VSMCs and that 3-hydroxy-3-methylglutaryl coenzyme
      A reductase inhibitors modulate EC accumulation. These data suggest a possible
      mechanism by which statins could contribute to the passivation and stabilization
      of actively growing atherosclerotic lesions.

PMID- 9598833
TI  - Phenotype interaction of apobec-1 and CETP, LDLR, and apoE gene expression in
      mice: role of apoB mRNA editing in lipoprotein phenotype expression.
AB  - Apolipoprotein (apo) B mRNA editing determines the amount of apoB-100 and apoB-48
      produced. Surprisingly, apobec-1 knockout mice, which do not edit apoB, have an
      essentially normal lipoprotein phenotype. By selected cross-breeding of mice of
      different genotypes, we show in this report that inactivation of editing produces
      profound phenotypic effects in cholesteryl ester transfer protein (CETP)
      transgenic mice and in apoE and low density lipoprotein receptor (LDLR) knockout
      mice. Compared with mice with an apobec-1+/+ background, CETP expression in
      apobec-1-/- mice caused a doubling of the plasma apoB-100 concentration (from
      3.5+/-0.6 to 8.8+/-1.9 mg/dL, P<.01) and a much greater shift of plasma
      cholesterol from HDL to IDL/LDL as assayed by fast protein liquid chromatography
      analysis; the ratio of non-HDL to HDL cholesterol was 0.47, 0.46, 0.76, and 1.43
      in apobec-1(+/+)/CETP-/-, apobec-1(-/-)/CETP-/-, apobec-1(+/+)/CETP+/-, and
      apobec-1(-/-)/CETP+/- animals, respectively. Feeding of a Western-type diet
      further exaggerated the shift in this ratio. In LDLR-/- mice, inactivation of
      apobec-1 caused an approximately 200% rise in plasma apoB-100 concentration, an
      approximately 60% increase in apoE concentration, and a 70% increase in total
      plasma cholesterol, which resulted exclusively from an increase in non-HDL
      cholesterol. The exaggerated hypercholesterolemia involving the VLDL+LDL
      fractions was further enhanced by a Western-type diet. In contrast, in apoE-/-
      mice, inactivation of apobec-1 caused a massive increase (from <0.5 to 55.5+/
      16.4 mg/dL) in plasma apoB-100 concentration but an approximately 55% reduction
      in hypercholesterolemia due to partial amelioration of the marked VLDL+IDL
      elevation. However, the difference in lipid profiles between apobec-1(+/+)/apoE-/
      and apobec-1(-/-)/apoE-/- mice was abolished in a time-dependent manner as
      further increases in total plasma cholesterol were induced by a Western-type
      diet. Whereas apobec-1 inactivation in wild-type mice produced little or no
      change in lipoprotein phenotype, giving rise to speculation that apoB mRNA
      editing does not have significant effect on lipoprotein dynamics, we show herein
      that there is important gene-gene interaction between apobec-1 and the CETP,
      LDLR, and apoE loci, which is subject to further substantial modulation by
      environmental factors such as a Western-type diet in mice.

PMID- 9598834
TI  - A common functional polymorphism in the promoter region of the microsomal
      triglyceride transfer protein gene influences plasma LDL levels.
AB  - Microsomal triglyceride transfer protein (MTP) is required for the assembly and
      cellular secretion of apolipoprotein B (apoB) -containing lipoproteins from the
      liver and intestine. The secretion pattern of apoB-containing lipoproteins is
      likely to influence the VLDL and LDL levels in plasma. By initial opportunistic
      screening for polymorphic sites in the regulatory region of the MTP gene by gene
      sequencing in 20 healthy male subjects, a common functional G/T polymorphism was
      detected 493 bp upstream from the transcriptional start point. There was
      differential binding of unique nuclear proteins at this site, as shown by
      electrophoretic mobility shift assay. The G variant seemed to bind two or three
      nuclear proteins that do not bind to the T variant. Expression studies with
      minimal promoter constructs linked to the chloramphenicol acetyltransferase
      reporter and transfected into HepG2 cells revealed marked enhancement of
      transcriptional activity with the T variant. The prevalence of the MTP promoter
      genotypes was investigated in a group of 184 healthy, middle-aged white men; the
      frequency of homozygosity for the MTP -493 T variant was .06 and the allele
      frequency of MTP -493T was .25 in the population. These homozygous subjects had a
      22% lower LDL cholesterol concentration than did heterozygotes or subjects
      homozygous for the MTP -493 G variant (2.9+/-0.6 versus 3.7+/-0.8 mmol/L, P<.05).
      Analysis of apoB and triglyceride contents in VLDL subfractions revealed a
      markedly changed balance within the VLDL population. Subjects homozygous for the
      MTP -493 T variant had fewer but more lipid-rich VLDL particles, thereby arguing
      for an effect of MTP expression on the hepatic secretion of triglyceride-rich,
      apoB-containing lipoproteins. This common genetic variation of the MTP promoter
      is likely to have important implications for cardiovascular disease.

PMID- 9598835
TI  - Relationship between insulin resistance and partially oxidized LDL particles in
      healthy, nondiabetic volunteers.
AB  - This study was performed in 36 healthy volunteers to define the relationship
      between plasma concentrations of partially oxidized low density lipoprotein
      (poxLDL), plasma glucose and insulin responses to oral glucose, and steady-state
      plasma glucose (SSPG) concentrations after a 180-minute infusion of somatostatin,
      insulin, and glucose. The concentration of poxLDL was estimated by determining
      the amount of conjugated dienes formed during in vitro LDL oxidation in the
      presence or absence of alanine. Under these conditions, the greater the in vitro
      antioxidant effect of alanine, the lower the amount of poxLDL that was present in
      plasma. The results demonstrated that plasma poxLDL concentration was
      significantly correlated with plasma glucose (r=.53, P<.001) and insulin (r=.43,
      P<.01) responses, SSPG concentrations (r=.53, P<.001), and plasma triglyceride
      (r=.42, P<.01) and HDL cholesterol (r=-.50, P<.002) concentrations. Furthermore,
      these relationships persisted when the data were corrected for differences in
      age, sex, body mass index, and the ratio of waist to hip girth. Of note, there
      was no correlation between poxLDL and LDL cholesterol concentration. When SSPG
      was entered along with age, sex, body mass index, and waist-to-hip ratio in a
      multiple regression model, SSPG alone was a significant prediction of poxLDL (r
      =.37, P<.02). The addition of plasma glucose and insulin responses and
      triglyceride and HDL cholesterol concentrations increased the r2 to only .47.
      These results show that the amount of poxLDL in plasma is significantly
      correlated with insulin resistance (ie, SSPG) and its metabolic consequences.

PMID- 9598836
TI  - Plasma viscosity and the risk of coronary heart disease: results from the MONICA
      Augsburg Cohort Study, 1984 to 1992.
AB  - Plasma viscosity is determined by various macromolecules, eg, fibrinogen,
      immunoglobulins, and lipoproteins. It may therefore reflect several aspects
      involved in cardiovascular diseases, including the effects of classic risk
      factors, hemostatic disturbances, and inflammation. We examined the association
      of plasma viscosity with the incidence of a first major coronary heart disease
      event (CHD; fatal and nonfatal myocardial infarction and cardiac death; n=50) in
      933 men aged 45 to 64 years of the MONICA project of Augsburg, Germany. The
      incidence rate was 7.23 per 1000 person-years (95% confidence interval [CI], 5.37
      to 9.53), and the subjects were followed up for 8 years. All suspected cases of
      an incident CHD event were classified according to the MONICA protocol. There was
      a positive and statistically significant unadjusted relationship between plasma
      viscosity and the incidence of CHD. The relative risk of CHD events associated
      with a 1-SD increase in plasma viscosity (0.070 mPa x s) was 1.60 (95% CI, 1.25
      to 2.03). After adjustment for age, total cholesterol, high density lipoprotein
      cholesterol, smoking, blood pressure, and body mass index, the relative risk was
      reduced only moderately (1.42; 95% CI, 1.09 to 1.86). The relative risk of CHD
      events for men in the highest quintile of the plasma viscosity distribution in
      comparison with the lowest quintile was 3.31 (95% CI, 1.19 to 9.25) after
      adjustment for the aforementioned variables. A large proportion of events (40%)
      occurred among men in the highest quintile. These findings suggest that plasma
      viscosity may have considerable potential to identify subjects at risk for CHD
      events.

PMID- 9598837
TI  - Differences in the metabolism of postprandial lipoproteins after a high
      monounsaturated-fat versus a high-carbohydrate diet in patients with type 1
      diabetes mellitus.
AB  - There is little information comparing the effects of a high-monounsaturated
      (Mono)-fat versus a high-carbohydrate (CHO) diet in patients with type 1 diabetes
      mellitus. In the present study, the effects of these diets on a number of
      metabolic parameters were compared. Seventeen normolipidemic, nonobese patients
      with type 1 diabetes were provided with the diets for 4 weeks each in a
      randomized, crossover design. The percentages of Mono fat of the two diets were
      25 Mono versus 9 CHO, with a corresponding total fat content of 40% versus 24%
      and a total CHO content of 45% versus 61%. At the end of each dietary period,
      parameters of glycemic control, coagulation factors, and fasting and postprandial
      lipoproteins were assessed. There were no differences in weight, glycemia,
      insulin dose, fasting lipid profile, or coagulation factors between the two
      diets. However, the metabolism of postprandial lipoproteins after a fat load
      differed; viz, after the Mono diet compared with the CHO diet, mean plasma
      triglyceride levels over 10 hours were higher (P=.0025, by repeated-measures
      ANOVA). The levels of triglyceride (P=.0045) and retinyl esters (P=.0046) in
      chylomicrons (Sf>400) and chylomicron remnants (Sf 100 to 400) (P=.0047 and
      P=.043, respectively), and the total particle number (apolipoprotein B levels) in
      chylomicron remnants (P=.001) and small, very low density lipoprotein (Sf 20 to
      100, P=.016) were also higher. Our data suggest that in patients with type 1
      diabetes, a CHO diet might be preferable to a Mono diet, since adherence to the
      former results in a lower number of circulating postprandial lipoprotein
      particles that are potentially atherogenic.

PMID- 9598838
TI  - Effects of atorvastatin on the intracellular stability and secretion of
      apolipoprotein B in HepG2 cells.
AB  - We investigated the effects of atorvastatin, a new 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, on the biogenesis of apolipoprotein B
      (apoB) in intact and permeabilized HepG2 cells. Intact cells were pretreated
      either with single or multiple doses of atorvastatin (0.1 to 20 micromol/L) for
      periods of 6 to 20 hours and pulsed with [35S]methionine. In some cases the cells
      were permeabilized with digitonin. Experiments were performed to investigate the
      effects of atorvastatin on (1) the rates of lipid synthesis and secretion, (2)
      the synthesis and accumulation of apoB, (3) the intracellular stability of apoB,
      (4) the amount of apoB-containing lipoprotein particles assembled in HepG2
      microsomes, and (5) the secretion and accumulation of apoB into the culture
      medium. ApoB synthesis, degradation, and secretion were measured by pulse-chase
      experiments with [35S]methionine in both intact and permeabilized HepG2 cells.
      Lipid synthesis was assessed by pulse-labeling experiments with [3H]acetate or
      [3H]oleate bound to bovine serum albumin. Comparisons were made under basal
      conditions and in the presence of oleate (0.36 micromol/L). Atorvastatin acutely
      inhibited the synthesis of cholesterol and cholesterol ester but did not have a
      significant effect on triglyceride or phospholipid synthesis. Atorvastatin did
      not affect the uptake of [35S]methionine by the cells nor did it influence the
      synthesis of apoB or a control protein, albumin. However, atorvastatin reduced
      the secretion of apoB into the culture medium, apparently by enhancing the
      degradation of apoB in the cell under basal and induced conditions with oleate.
      The stability of apoB associated with the lipoprotein particles was also
      significantly lowered by atorvastatin. The stimulated degradation of apoB in
      atorvastatin-treated cells was sensitive to MG132, a proteasome inhibitor. The
      net effect of atorvastatin was a reduction in the number of apoB-containing
      lipoprotein particles of different sizes isolated from microsomes and a reduction
      in apoB secretion into the culture medium. The data suggest that atorvastatin may
      impair the translocation of apoB into the lumen of the endoplasmic reticulum,
      thus increasing the amount of apoB degraded intracellularly. It is hypothesized
      that atorvastatin alters these parameters primarily as a result of inhibiting
      cholesterol synthesis and limiting the availability of cholesterol and/or
      cholesterol ester for the normal assembly of apoB-containing lipoprotein
      particles.

PMID- 9598839
TI  - Minimally oxidized low-density lipoprotein increases expression of scavenger
      receptor A, CD36, and macrosialin in resident mouse peritoneal macrophages.
AB  - Fully oxidized LDL (OxLDL) is believed to contribute to atherogenesis in part by
      virtue of uptake into macrophages via specific scavenger receptors. This
      phenomenon results in the formation of cholesterol-loaded foam cells, a major
      component of atherosclerotic lesions. The present study is directed at examining
      the effects of OxLDL and minimally oxidized LDL (MM-LDL) on scavenger receptor
      expression and activity in mouse peritoneal resident macrophages. Macrophages
      were preincubated with MM-LDL or OxLDL at concentrations of 25 or 50 microg/mL
      for 24 to 48 hours, after which their ability to bind and take up 125I-OxLDL or
      125I-acetylated LDL (AcLDL) was determined. MM-LDL pretreatment induced a clear
      increase of cell association and degradation of 125I-OxLDL and 125I-AcLDL.
      Pretreatment with OxLDL also enhanced scavenger receptor activity, but to a
      lesser degree. Neither native LDL nor AcLDL had any effect. Scatchard analysis
      showed that preincubation with 50 microg/mL MM-LDL for 48 hours increased the
      Bmax of 125I-OxLDL and 125I-AcLDL by 139% and 154%, respectively, without
      significantly changing their affinity. Lipids extracted from MM-LDL also
      significantly induced scavenger receptor activity, but to a lesser extent than
      did intact MM-LDL. MM-LDL pretreatment increased both mRNA levels and protein
      levels of scavenger receptor A, CD36, and macrosialin. On the other hand, OxLDL
      pretreatment increased expression of macrosialin only. These results, showing
      that MM-LDL can upregulate scavenger receptor expression in mouse resident
      peritoneal macrophages, suggest that clearance of OxLDL by macrophages in lesions
      is more effective, in part because the OxLDL precursor, MM-LDL, primes the
      macrophage for foam cell generation.

PMID- 9598841
TI  - Elevated expression of urokinase-like plasminogen activator and plasminogen
      activator inhibitor type 1 during the vascular remodeling associated with
      pulmonary thromboembolism.
AB  - Information is lacking on the mechanisms involved in the organization,
      resolution, and repair of the vascular lumen after acute pulmonary
      thromboembolism. Because recent data suggest that the balance between plasminogen
      activators (PAs) and type 1 plasminogen activator inhibitor (PAI-1) plays a role
      in regulating cell migration within the extracellular matrix, we investigated the
      expression of these molecules by immunohistochemical and in situ hybridization
      analysis of pulmonary artery specimens from patients suffering fatal pulmonary
      embolism. The data were compared with the expression of these molecules in both
      patients' noninvolved pulmonary arteries and organ donor pulmonary arteries.
      Regions of initial organization and vascular remodeling were identified by a
      modified trichrome stain and by the presence of proliferating cell nuclear
      antigen (PCNA), a cell marker of proliferation. Staining for tissue-type PA
      antigen was low to undetectable in endothelial cells directly in contact with the
      fibrin-platelet thromboembolus and in areas in which the endothelial cell lining
      was replaced by cell growth into the thrombus. Urokinase-like PA (u-PA)
      expression was detected in mononuclear cells within the thrombus in the initial
      phase of thromboembolism and within cells migrating into the thrombus during the
      later stages of organization. PAI-1 expression was elevated in the monolayer of
      endothelial cells underlying the fresh platelet-fibrin thromboembolus and in a
      PCNA-positive cell population present between the pulmonary arterial intima and
      the thromboembolus that represents early organization. Increased expression of
      PAI-1 may play a role in inhibiting proteolysis and fostering the localization of
      the acute fibrin-platelet thrombus to the vascular wall, which is followed by the
      upregulation of u-PA in migrating cells during the reorganization process.

PMID- 9598840
TI  - Metalloproteinase blockade by local overexpression of TIMP-1 increases elastin
      accumulation in rat carotid artery intima.
AB  - We have recently demonstrated that the blockade of matrix metalloproteinases by
      local overexpression of the intrinsic inhibitor tissue inhibitor of matrix
      metalloproteinase-1 (TIMP-1) reduces intimal hyperplasia. We now report a major
      change in the elastin content of the intima of rat carotid arteries seeded with
      TIMP-1-overexpressing smooth muscle cells. To understand the mechanism
      responsible for elastin accumulation, synthesis and degradation of elastin in
      TIMP-1 and control cell-seeded rats were measured. There were no differences in
      elastin mRNA or elastin synthesis, as documented by 14[C]proline incorporation
      between TIMP-1 and control cell-seeded arteries. In contrast, there was an
      increase in cross-linked elastin in the TIMP-1 group. In addition, in TIMP-1 and
      control rats, an elastase activity of approximately 28 kD was detected by elastin
      zymography and was decreased in TIMP-1 cell-seeded vessels. The 28 kD elastolytic
      activity was inhibited by exogenously added TIMP-1 and EDTA but not by PMSF,
      suggesting that it was a metalloelastase. Therefore, we have demonstrated that a
      shift of the proteolytic balance toward protease inhibition by TIMP-1
      overexpression does not change elastin synthesis but rather changes
      posttranslational processing, resulting in increased elastin accumulation.

PMID- 9598842
TI  - Pretreatment of rabbits with either hirudin, ancrod, or warfarin significantly
      reduces the immediate uptake of fibrinogen and platelets by the deendothelialized
      aorta wall after balloon-catheter injury in vivo.
AB  - Fibrinogen and platelets rapidly saturate the exposed subendothelium of a freshly
      deendothelialized aorta in vivo. As thrombin generated within the site of injury
      is largely responsible for fibrin(ogen) deposition, we questioned whether various
      anticoagulant treatments would inhibit uptake of both fibrinogen and platelets in
      vivo. Rabbits were anticoagulated by pretreatment with either Warfarin, Ancrod,
      or recombinant hirudin. Each anesthetized, anticoagulated (or saline-injected
      control) rabbit was injected i.v. with rabbit 51Cr-platelets and 125I-fibrinogen
      before a balloon-catheter deendothelializing (or sham) injury of the thoracic
      aorta. At 10 minutes after injury, the rabbit was exsanguinated and the aorta
      excised. Platelet adsorption by the deendothelialized aorta surface was
      substantially reduced in anticoagulated rabbits (controls, 2.2x10(5)/mm2;
      Warfarin-treated, 1.2x10(5)/mm2; Ancrod-treated, 5.3x10(4)/mm2; r-hirudin-treated
      [5 mg/kg], 5.3x10(4)/mm2), and a significant reduction of fibrinogen associated
      with the platelet layer (from 5.3 to 1 to 2 pmol/cm2) and within the underlying
      intima-media layer (from 16.9 to 5 to 6 pmol/cm2) was observed in the r-hirudin
      and Warfarin-treated rabbits. The pattern of aorta-deposited 51Cr-platelets and
      125I-fibrin in the anticoagulated rabbits corresponded well with an assessment by
      transmission electron microscopy of aortic tissue samples. We conclude that
      approximately 70% of fibrinogen uptake is thrombin dependent and that
      approximately 80% of platelet adsorption depends on codeposited fibrin(ogen)
      during the 10-minute interval after balloon injury. Pretreatment with an agent
      that interferes with either thrombin or fibrin production will inhibit the
      immediate interaction of fibrinogen and platelets with the freshly exposed
      subendothelium.

PMID- 9598843
TI  - Differential expression of functional protease-activated receptor-2 (PAR-2) in
      human vascular smooth muscle cells.
AB  - The protease-activated family of G protein-coupled receptors includes PAR-1 and
      PAR-3, which are activated by thrombin, and PAR-2, which is activated by trypsin
      and tryptase. PAR-2 has recently been shown to be expressed in human endothelial
      cells. In the present studies, we have examined the expression of PAR-2 in other
      cells, particularly vascular smooth muscle, and tested whether the receptors are
      functional. The results show that PAR-2 is present in human aorta and coronary
      artery smooth muscle cells, as well as in arteries traversing the walls of the
      small intestine. It was also detected in human keratinocytes, sweat glands,
      intestinal smooth muscle, and intestinal epithelium, but not at all in myocardial
      smooth muscle and only inconsistently in intestinal veins and venules. Activation
      of aortic smooth muscle cells in culture with PAR-2 peptide agonists caused a
      transient increase in the cytosolic Ca2+ concentration. In contrast, PAR-2 mRNA
      could not be detected in saphenous vein smooth muscle cells, and the same cells
      placed in culture showed little, if any, response to the PAR-2 agonist peptides.
      These observations show that PAR-2 is widely distributed in human vascular smooth
      muscle, particularly in arteries. However, this is not a universal finding and at
      least some venous smooth muscle cells, including those in saphenous veins,
      apparently do not express the receptor in detectable amounts.

PMID- 9598844
TI  - No effect of consumption of green and black tea on plasma lipid and antioxidant
      levels and on LDL oxidation in smokers.
AB  - Intake of flavonoids is associated with a reduced cardiovascular risk. Oxidation
      of LDL is a major step in atherogenesis, and antioxidants may protect LDL from
      oxidation. Because tea is an important source of flavonoids, which are strong
      antioxidants, we have assessed in a randomized, placebo-controlled study the
      effect of consumption of black and green tea and of intake of isolated green tea
      polyphenols on LDL oxidation ex vivo and on plasma levels of antioxidants and
      lipids. Healthy male and female smokers (aged 34+/-12 years, 13 to 16 per group)
      consumed during a 4-week period 6 cups (900 mL) of black or green tea or water
      per day, or they received as a supplement 3.6 grams of green tea polyphenols per
      day (equivalent to the consumption of 18 cups of green tea per day). Consumption
      of black or green tea had no effect on plasma cholesterol and triglycerides, HDL
      and LDL cholesterol, plasma vitamins C and E, beta-carotene, and uric acid. No
      differences were found in parameters of LDL oxidation. Intake of green tea
      polyphenols decreased plasma vitamin E significantly in that group compared with
      the control group (-11% P=.016) but had no effect on LDL oxidation ex vivo. We
      conclude that consumption of black or green tea (6 cups per day) has no effect on
      plasma lipids and no sparing effect on plasma antioxidant vitamins and that
      intake of a high dose of isolated green tea polyphenols decreases plasma vitamin
      E. Although tea polyphenols had a potent antioxidant activity on LDL oxidation in
      vitro, no effect was found on LDL oxidation ex vivo after consumption of green or
      black tea or intake of a green tea polyphenol isolate.

PMID- 9598845
TI  - Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the
      endothelium in the ApoE-deficient mouse.
AB  - Focal recruitment of monocytes and lymphocytes is one of the earliest detectable
      cellular responses in the formation of lesions of atherosclerosis. This localized
      accumulation of leukocytes is a multistep process in which the endothelium
      remains intact and may regulate leukocyte recruitment by expressing specific
      adhesion molecules. To examine the relationship of adhesion molecule expression
      to initiation factors and the sites of lesion formation, we analyzed the
      expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion
      molecule-1 (ICAM-1), and platelet-endothelial cell adhesion molecule-1 (PECAM-1)
      en face on the aortic endothelium of control mice and homozygous apolipoprotein E
      deficient (ApoE -/-) mice that develop complex lesions of atherosclerosis similar
      to those in humans. In control mice, VCAM-1 staining was weak and limited to
      sites of altered blood flow. In contrast, in the ApoE -/- mice, VCAM-1 appeared
      to be localized over the surface of groups of endothelial cells in lesion-prone
      sites. Expression of VCAM-1 preceded lesion formation, and increased expression
      above control levels appeared to be correlated with the extent of exposure to
      plasma cholesterol. Although ICAM-1 was the most prominent adhesion molecule in
      lesion-prone sites, its expression appeared to be independent of plasma
      cholesterol levels and was upregulated in both ApoE -/- and control mice. At
      lesion-prone sites associated with altered blood flow, ICAM-1 was located over
      the surface of each endothelial cell and on microvilli, whereas VCAM-1 was
      confined to the cell periphery in non-lesion-prone sites. PECAM-1 was localized
      at the cell periphery throughout the aorta, and its expression did not appear to
      be regulated. Thus, the levels, localization, and characteristics of expression
      of VCAM-1, ICAM-1, and PECAM-1 appear to be differentially regulated.
      Upregulation of VCAM-1 and ICAM-1 is associated with sites of lesion formation.

PMID- 9598846
TI  - Child fatality review in Georgia: a young system demonstrates its potential for
      identifying preventable childhood deaths.
AB  - BACKGROUND: Child fatality review (CFR) by interagency teams can contribute to
      the prevention of childhood deaths. We investigated the potential usefulness of
      Georgia's CFR, legislated in 1990 primarily to prevent death from child
      maltreatment, for identifying preventable deaths from injury and sudden infant
      death syndrome (SIDS). METHODS: Using CFR report data and death certificate data,
      we examined reviewed and nonreviewed childhood deaths in Georgia in 1991 and
      examined data by etiology, county, risk factors, and preventability. RESULTS:
      Injury or SIDS caused 33.2% of childhood deaths in Georgia in 1991; CFR reviewed
      29.4% of these. Child fatality review was most sensitive for investigating death
      from intentional injury (40.5%) and SIDS (35.3%). Review teams reassigned the
      cause of five deaths (2.0%) to child abuse or neglect. County participation was
      low (31.4%). Overall, 29.0% of deaths were judged preventable. CONCLUSIONS:
      Georgia's CFR has potential for identifying preventable childhood deaths.
      Refinements in the system can increase the number and accuracy of death
      investigations. By participating in the system, physicians may make meaningful
      contributions to preventing childhood death in their own communities.

PMID- 9598847
TI  - Legal and ethical dilemmas in drug management for team physicians and athletic
      trainers.
AB  - Increasing violations of prescription drug regulations should alert physicians,
      trainers, and physiotherapists at collegiate and professional levels. Failure to
      adhere to state and federal requirements can have severe consequences for both
      physician and nonphysician practitioners. Training manuals that include a chapter
      on drug management will not allow disciplinary powers in themselves, but will put
      the problems in proper perspective for athletic trainers.

PMID- 9598848
TI  - Delirium tremens.
AB  - BACKGROUND: The hyperadrenergic syndrome, delirium tremens, as contrasted with
      tile milder alcohol withdrawal syndromes, is a medical emergency. The clinical
      features of delirium tremens were carefully described almost 200 years ago. Since
      then, many therapies have been suggested as superior to preceding therapeutic
      approaches. Unfortunately, morbidity and mortality remain relatively unchanged
      for the last 100 years. METHODS: Using a literature review, we review the history
      of delirium tremens, including the suggested therapeutic approaches.
      RESULTS/CONCLUSIONS: We recommend a rational approach to management and therapy,
      based on present knowledge.

PMID- 9598849
TI  - Continuous non-seasonal epidemic of respiratory syncytial virus infection in the
      southeast United States.
AB  - BACKGROUND: This study was done to define the seasonality of respiratory
      syncytial virus (RSV) epidemics in the southeastern United States. METHODS: We
      tested 5,092 fresh nasal aspirates or washings, using the Kallestad Pathfinder
      enzyme immunoassay (EIA) or the Directigen RSV membrane EIA according to
      manufacturers' directions. RESULTS: A total of 1,419 (27.9%) respiratory
      specimens, collected from pediatric patients between May 1993 and December 1996
      at two large southeastern medical centers, were positive for RSV antigen by
      enzyme immunoassay. A persistent RSV epidemic was documented between July 1993
      and December 1996. We defined an epidemic as 2 consecutive months in each of
      which > or = 10% of the specimens were positive and > or = 2 positive specimens
      detected. The highest percentages of positive specimens were detected in December
      of 1993, 1994, and 1996, to date, and November 1995. CONCLUSION: On the basis of
      our findings, we recommend health care workers consider RSV in the differential
      diagnosis of acute respiratory illness throughout the year in pediatric patients
      from the southeast United States.

PMID- 9598850
TI  - Medication and low serum thyroxine values in nursing home residents.
AB  - BACKGROUND: The nursing home clinician may encounter euthyroid residents with low
      total serum thyroxine (T4) values associated with certain medications or
      nonthyroidal illness (NTI). Hypothyroidism may be incorrectly diagnosed and
      thyroid hormone prescribed. METHODS: We reviewed all T4 determinations and
      individuals with low T4 and normal thyroid-stimulating hormone (TSH) levels were
      identified. Pharmacy and medical records were reviewed. RESULTS: We reviewed
      1,153 T4 determinations and identified 22 individuals with low T4 and normal TSH
      values. Eight of the 22 (36%) were being treated with high-dose salicylates, 4
      (18%) with phenytoin, 3 (14%) with carbamazepine, and 2 (9%) with prednisone (15
      mg/day). Three residents were on two of these medications. None was on prednisone
      as a single medication. Eight were on none of the medications, and 5 of these had
      albumin values of < or = 3.2 g/dL (a marker of NTI). After a low T4 value was
      determined in these individuals, 6 of the 22 were placed on T4 replacement with
      no documentation of hypothyroidism. In 5 of these, low T4 level could be
      attributed to a medication effect. CONCLUSIONS: Low total T4 with normal TSH
      levels are commonly associated with medications and NTI.

PMID- 9598851
TI  - Maternal mortality associated with adult respiratory distress syndrome.
AB  - BACKGROUND: Pregnancy-related adult respiratory distress syndrome (ARDS) can lead
      to maternal mortality and morbidity. METHODS: Records of all pregnant patients
      diagnosed with ARDS over a 14-year period were reviewed and the cases were
      stratified into survivors and nonsurvivors. RESULTS: Forty-one cases were
      identified and 31 survived (maternal mortality rate of 24.4%). Adult respiratory
      distress syndrome was diagnosed in the antepartum period in 23 (56.1%) of the
      patients and the majority of these cases occurred in the third trimester (73.9%).
      There was no statistically significant difference in demographic characteristics,
      preexisting diseases, or probable precipitating cause for the development of ARDS
      between the two groups. The cause of death among the nonsurvivors included
      multisystem organ failure, sepsis, cardiac arrest, and disseminated intravascular
      coagulopathy. CONCLUSION: Pregnancy-related ARDS continues to be associated with
      a high maternal mortality rate (25%). Unfortunately, the etiology for ARDS during
      pregnancy is not predictive of maternal outcome.

PMID- 9598852
TI  - Clinical experience with the Storz Modulith SL 20 lithotriptor.
AB  - BACKGROUND: A Food and Drug Administration pre-market approval study evaluated
      the safety and effectiveness of the Storz Modulith SL 20 lithotriptor. METHODS:
      Protocol was a maximum of 2,000 shock waves per treatment and no more than three
      treatments per patient. Safety and effectiveness parameters were defined and
      followed. RESULTS: The overall success rate was 74.6% with a stone-free rate of
      63.6%. No clinically or statistically significant adverse trends were noted
      acutely or in follow-up. CONCLUSIONS: The Storz Modulith SL 20 lithotriptor is a
      safe and effective device to treat renal and ureteral calculi in an outpatient
      setting using intravenous sedation/analgesia.

PMID- 9598853
TI  - Ulnar nerve entrapment at the wrist: cases from a hand surgery practice.
AB  - BACKGROUND: Eight patients with 11 instances of wrist-level ulnar nerve
      entrapment, a fairly uncommon compression syndrome, were identified in a hand
      surgery practice from 1992 through 1996. METHODS: Presentations, causes, and
      surgical outcomes were examined, and the pertinent literature was reviewed.
      RESULTS: All eight patients had extrinsic, nonidiopathic compression of the ulnar
      nerve caused by tumor, vascular disease, anomalous muscle development, or a tight
      fibrous arch at the origin of the flexor digiti minimi. In all cases, sensory
      symptoms resolved with removal of the cause of ulnar nerve compression.
      CONCLUSIONS: These cases serve to remind physicians that not every instance of
      numbness and tingling in the hand represents carpal tunnel syndrome. Careful
      clinical examination may not only localize compression of the ulnar nerve at
      wrist level but also may reveal its etiology. Some causes of ulnar compressive
      neuropathy, however, are apparent only with surgical exploration.

PMID- 9598854
TI  - DRG reimbursement: geriatric hip fractures in the community hospital trauma
      center.
AB  - BACKGROUND: The purpose of this paper was to determine whether Medicare
      reimbursement for hip fracture reaches cost in geriatric patients. METHODS: We
      conducted a retrospective review using the hospital trauma registry.
      Demographics, operations, length of stay, clinical outcome, discharge
      disposition, hospital charges, and hospital costs were reviewed and compared with
      diagnosis-related group (DRG) reimbursement. RESULTS: The study included 153
      Medicare patients. Mortality was 3.9%, 71% were discharged to a nursing home or
      rehabilitation unit, and 25% went directly home. DRG reimbursement constituted
      58% of charges. Compared with costs, the DRG amount represented a mean loss of
      nearly $1,000 per patient. CONCLUSIONS: DRG reimbursement undercompensates the
      community hospital trauma center for treating a common malady among the geriatric
      population. A population shift toward the elderly, decreasing Medicare
      remuneration, and the advance of managed care will make correct identification
      and control of costs extremely important for the hospital caring for hip
      fractures in the geriatric population.

PMID- 9598855
TI  - Carcinoma of the colon: an unusual cause of prolonged fever.
AB  - Solid tumors rarely present with fever. Among those that do, carcinoma of the
      colon has been infrequently reported as a primary cause of fever. This patient
      had carcinoma of the right colon with prolonged fever, but no evidence of
      infection or gastrointestinal symptoms. At surgical resection, a caecal
      adenocarcinoma was found with metastases to the mesentery and 10 of 40 lymph
      nodes. The patient's fever resolved after 3 days. The patient remained healthy
      during 8 years of follow-up. Right-sided colon cancer is not often considered in
      the complete evaluation of fever of undetermined cause.

PMID- 9598856
TI  - Chromobacterium violaceum infection.
AB  - Chromobacterium violaceum infection is confined to the tropical and subtropical
      areas, with almost all reported cases occurring in the Southeast. The most common
      feature of this infection is sepsis, followed by cutaneous involvement and liver
      abscesses. Treatment consists of surgical drainage of purulent collections and
      appropriate antimicrobial therapy, such as chloramphenicol, gentamicin, imipenem,
      trimethoprim-sulfamethoxazole, or ciprofloxacin. Although C violaceum infection
      is rare, it is potentially fatal and remains an important entity for clinicians
      to suspect and treat appropriately.

PMID- 9598857
TI  - Acute tumor lysis syndrome after transcatheter chemoembolization of
      hepatocellular carcinoma.
AB  - Two cases of acute tumor lysis syndrome occurring in patients with hepatocellular
      carcinoma are reported. Both patients were treated with transcatheter
      chemoembolization. Tumor lysis syndrome was not anticipated in the first case and
      was diagnosed late. However, the second patient's syndrome was detected early and
      treated appropriately. Subtle changes in electrolytes may be missed because of
      aggressive hydration that many of these patients receive because of cisplatin
      therapy. I propose that all patients with large hepatoma, particularly those with
      a short history, be monitored closely for acute tumor lysis syndrome.

PMID- 9598858
TI  - Hypersensitivity reaction to azathioprine.
AB  - Adverse drug reactions can vary from a simple rash to anaphylactic shock. While
      certain medications including the penicillins are well known to cause such
      reactions, other drugs are not as commonly recognized. Azathioprine
      hypersensitivity reactions tend to be benign and self-limiting with cessation of
      drug ingestion. We report a patient who had a hypersensitivity reaction to
      azathioprine, which manifested as distributive shock that mimicked sepsis. We
      also reviewed the English language literature for risk factors for a
      hypersensitivity reaction to azathioprine and its possible mechanism.

PMID- 9598859
TI  - Management of primary hyperparathyroidism in children.
AB  - Primary hyperparathyroidism is unusual in children. It is most commonly due to a
      solitary sporadic parathyroid adenoma, though parathyroid hyperplasia and related
      familial syndromes should be considered. In the case presented here, an 11-year
      old boy with primary hyperparathyroidism had preoperative imaging studies that
      localized to the inferior aspect of the left side of the neck anteriorly, and a
      parathyroid adenoma was successfully resected. Screening for familial syndromes
      involving hyperparathyroidism should be individually considered in children with
      primary hyperparathyroidism. Preoperative localizing studies and the role of
      unilateral surgery are controversial issues in adults with primary
      hyperparathyroidism. Although such issues have not been addressed in children,
      localization and unilateral surgery proved successful in this case.

PMID- 9598860
TI  - Serous psammocarcinoma of the ovary.
AB  - We present the case of a 59-year-old woman with an International Federation of
      Gynecology and Obstetrics stage IIIB serous psammocarcinoma. Only 12 cases of
      this rare ovarian neoplasm have been reported previously. These tumors act like
      borderline tumors and, therefore, do not usually require chemotherapy or
      radiation therapy after appropriate surgical debulking and staging.

PMID- 9598862
TI  - Hemoptysis as the sole presentation of Pasteurella multocida infection.
AB  - Pasteurella multocida has been implicated as the cause of a variety of
      respiratory conditions (eg, bronchitis, pneumonia, lung abscess, empyema), but
      hemoptysis has been noted only in conjunction with other lung conditions. We
      report a case in which hemoptysis was the sole manifestation of Pasteurella
      infection. The patient was a middle-aged man with severe obstructive lung disease
      and exposure to cats. Diagnosis was made by bronchoscopy and high-dose penicillin
      was required for resolution.

PMID- 9598861
TI  - 'Surgiceloma' manifested as cauda equina syndrome.
AB  - A 28-year-old man needed urgent decompression because of development of cauda
      equina syndrome 36 hours after an operation for disk degeneration and spinal
      stenosis. At reexploration, swollen blood-soaked Surgicel (a hemostatic agent)
      was found to be the only cause of compression. Six months after the operation,
      the patient was able to work full time.

PMID- 9598863
TI  - Fatal and near-fatal complications of liposuction.
AB  - Cosmetic liposuction is considered to be safe and effective in properly selected
      patients and is widely done as an outpatient or office procedure. When major
      complications occur, office-based practitioners may refer patients to a hospital
      emergency department, where medical personnel unfamiliar with this procedure may
      underestimate the risk of serious infection or other major complications. We
      present two cases of massive necrotizing fasciitis treated in a burn center after
      liposuction surgery. One patient died, and the second required lengthy
      hospitalization, extensive debridement, and split-thickness skin grafting of 22%
      of the total body surface area. Pain out of proportion to clinical findings is a
      hallmark of necrotizing fasciitis and should prompt consideration of this entity
      even in the absence of cutaneous signs of infection. Definitive diagnosis is made
      by biopsy and rapid section histologic analysis. Liposuction may result in major
      complications or death. Emergency department physicians or general surgeons may
      be called upon to manage such complications and should be aware of these risks.

PMID- 9598864
TI  - Chronic myelogenous leukemia and porphyria cutanea tarda in a patient with
      limited systemic sclerosis.
AB  - Systemic sclerosis is uncommonly associated with hematologic malignancies. We
      report the case of a patient who had chronic myelogenous leukemia 3 years after
      the CREST variant of systemic sclerosis was diagnosed. She also later had
      porphyria cutanea tarda. The majority of patients who had hematologic
      malignancies after the diagnosis of systemic sclerosis proved to have either
      multiple myeloma or chronic lymphocytic leukemia. Hematologic malignancies may be
      found in patients with systemic sclerosis (either limited or diffuse).

PMID- 9598865
TI  - Migration of wire mesh into the intestinal lumen causing an intestinal
      obstruction 30 years after repair of a ventral hernia.
AB  - Wire mesh repair of abdominal wall hernias was abandoned almost four decades ago.
      Recently, a woman who had a wire mesh repair of an incisional hernia in 1964 came
      to the emergency room with a complete small bowel obstruction. The obstruction
      was caused by a segment of wire mesh that broke off from the abdominal wall and
      migrated into the small bowel lumen. During the preceding 2 years, she had been
      evaluated by two different gastroenterologists for chronic anemia, but they
      failed to obtain an evaluation of the small intestine. This case report shows
      that abdominal foreign bodies may migrate into the intestinal tract. I recommend
      that an evaluation of chronic anemia in the geriatric patient include evaluation
      of the small intestine.

PMID- 9598867
TI  - The extent of surgery and prognosis of patients with phyllodes tumor of the
      breast.
AB  - In an attempt to clarify the controversial issues related to prognosis and
      therapeutic aspects of phyllodes tumors (PT), we retrospectively reviewed all
      cases of PT treated in our hospital during the last fifteen years. Re-examining
      the pathology material we found 84 cases, while thirteen more cases which had
      been initially classified as fibroadenomas with areas of phyllodes tumor were
      rejected from the analysis because they were classified as fibroadenomas. Based
      on the criteria proposed by Azzopardi and Salvadori and adopted by WHO, we found
      55 benign PT (65.14%), 14 borderline PT (16.6%), and 15 malignant PT (17.8%). The
      median age of the patients with benign PT was 34 years, compared to 46.5 years
      for those with borderline tumors and 52 years for those with malignant. The
      median size of benign tumors was 3 cm, 9.5 cm for borderline, and 7.25 cm for
      malignant. Out of 55 patients with benign PTs, 37 underwent wide local excision
      and the remaining 18, with small tumors, underwent enucleation. In this group of
      patients, there was no recurrence after a median interval of 6.65 years. Eleven
      patients with borderline PT underwent wide local excision and three mastectomy;
      one immediately after an incomplete PT excision and the remaining two 8 months
      and 2 years later due to a locally recurrent PT (the last one proven
      histologically in the permanent biopsy of the recurrence to be malignant). Twelve
      patients with malignant PT underwent mastectomy, either during the same operation
      or following the results of the permanent section biopsy. Three more patients
      with malignant PT underwent wide local excision. The size of the tumor in these
      patients was relatively small and the pathology report indicated clear margins
      with normal breast tissue surrounding the tumor. One patient with 8 cm diameter
      malignant PT, who underwent mastectomy, passed away sixteen months later from
      widely spread metastases. Applying the criteria of Azzopardi and Salvadori, each
      case of PT can be managed successfully avoiding unnecessary mastectomies.

PMID- 9598866
TI  - Effects of sulindac and its metabolites on growth and apoptosis in human mammary
      epithelial and breast carcinoma cell lines.
AB  - Nonsteriodal anti-inflammatory drugs (NSAIDs) are among the most commonly used
      medications in the United States and elsewhere, mainly for the treatment of
      arthritis. The NSAID sulindac causes regression and prevents the recurrence of
      premalignant colonic polyps in patients with familial adenomatous polyposis and
      inhibits colon carcinogenesis in rodents. Sulindac and sulindac sulfone, a
      metabolite of sulindac that lacks cyclooxygenase (cox) inhibitory activity, also
      inhibit mammary carcinogenesis in rats. To obtain insights into the relevance of
      these findings to human breast cancer, we examined the mechanism of action of
      sulindac and its sulfide and sulfone metabolites on the normal human mammary
      epithelial cell line MCF-10F and the human breast cancer cell line MCF-7. Of the
      three compounds, the sulfide was the most potent inhibitor of cell growth,
      although the sulfone and sulfoxide were also active at higher concentrations.
      Treatment of MCF-10F and MCF-7 cells with 100 microM sulindac sulfide resulted in
      accumulation of cells in the G1 phase of the cell cycle and induction of
      apoptosis. Apoptosis occurred within 24 h as determined by the TUNEL assay and
      DNA laddering was observed at 72 h. The accumulation of cells in G1 was
      associated with decreased levels of expression of cyclin D1 but no effect was
      seen on the expression of CDK4 or the immediate early response gene c-jun.
      Treatment with sulindac sulfide caused a striking induction of the CDK inhibitor
      p21WAF1 in MCF-10F cells. The MCF-7 cell line expressed a high basal level of
      p21WAF1 which did not change significantly after drug treatment. The pro
      apoptotic gene BAX was not induced in either MCF-10F or MCF-7 cells by sulindac
      sulfide. Stable overexpression of cyclin D1, which frequently occurs in breast
      cancers, did not protect mammary epithelial cells from inhibition by the sulfide.
      These studies suggest that this class of compounds warrants further study with
      respect to breast cancer prevention and treatment.

PMID- 9598868
TI  - Ultrastructural characterization and biochemical profile of human gross cystic
      breast disease.
AB  - Human gross cystic breast disease is a benign condition affecting about 7-10% of
      adult women occurring with the highest incidence in the premenopausal decade.
      Although breast cysts do not represent a preneoplastic condition per se, several
      studies indicate an increased breast cancer risk in women affected by this
      pathology. In this report we study 115 breast cystic fluid samples obtained by
      needle-aspiration from women with gross cystic breast disease. The samples were
      analysed biochemically and the cells contained therein were observed at the
      electron microscope. According to their biochemical profiles, the cysts were
      subdivided into three types: Type I, showing a Na/K ratio < 0.5 and a typical
      protein content; Type II, showing a Na/K ratio >10 and a protein content quite
      similar to plasma; Type III, showing a Na/K ratio between 1 and 7 and an
      intermediate protein content. The electron microscopic examination demonstrated
      that Type I cystic fluid cells exhibit morphological features typical of actively
      synthesising and secreting cells, while the characteristics of Type II cells
      indicate a low metabolic activity. Type III cells have characteristics typical of
      both Type I and Type II cells, thereby confirming the intermediate nature of this
      cyst type. We hypothesise that these cyst types could represent different
      developmental stages of a structural evolution pathway, during which the
      biosynthetically active 'apocrine stage' would be the key step to cell neoplastic
      transformation.

PMID- 9598869
TI  - Effects of conjugated estrogens, medroxyprogesterone acetate, and tamoxifen on
      the mammary glands of macaques.
AB  - The purpose of this work was to examine the mammary glands of adult,
      ovariectomized female cynomolgus macaques (Macaca fascicularis) in a long-term
      study of the effects of hormone treatments on chronic disease. Treatments
      included conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA),
      CEE+MPA, and tamoxifen. Doses were scaled from those given women. Treatments were
      given in the diet for three years, followed by necropsy and tissue collection.
      Endpoints evaluated included glandular histology, histomorphometry, and
      immunohistochemical detection of the proliferation marker Ki-67, estrogen
      receptor (ER), and progesterone receptor (PR) in mammary epithelial cells. Major
      findings were as follows: CEE induced PR expression and focal to diffuse
      lobuloalveolar proliferation. Proliferation was increased by the addition of MPA,
      but was not induced by MPA alone. Tamoxifen induced ER and PR but not Ki-67
      expression or glandular hyperplasia. Neoplasms were not seen. These findings
      indicate that progestogens may exacerbate, not antagonize mammary gland
      proliferation induced by estrogen replacement therapy, and that tamoxifen has
      both estrogen agonist and antagonist effects on sex steroid receptor expression
      in the normal primate breast.

PMID- 9598870
TI  - Progesterone receptor variants found in breast cells repress transcription by
      wild-type receptors.
AB  - Progesterone, through its nuclear receptors (PR), regulates the development and
      growth of breast cancers. PR also serve as markers of hormone dependence and
      prognosis in patients with this disease, and functional PR are required to
      mediate the antiproliferative effects of progestin therapies. We find that normal
      and malignant breast cells and tissues can express anomalous forms of PR
      transcripts. We have isolated four variant PR mRNAs that contain precise
      deletions of exons encoding sections of the DNA- and hormone-binding domains. The
      transcripts lack exon 2 (PRdelta2), exon 4 (PRdelta4), exon 6 (PRdelta6), or
      exons 5 and 6 (PRdelta5,6). On immunoblots, PRdelta4, delta6. and delta5, 6
      cloned into the background of the PR A-isoform comigrate with similar proteins
      present in breast tumor extracts; delta6 and delta5, 6 are dominant-negative
      transcriptional inhibitors of wild-type A- and B-receptors. We propose that
      expression of variant PR can compromise the accuracy of receptor measurements as
      markers of hormone-dependent cancers, and can modify the responses of tumors to
      progestin therapies.

PMID- 9598871
TI  - Polyamine inhibition of estrogen receptor (ER) DNA-binding and ligand-binding
      functions.
AB  - Polyamines are known to inhibit sequence specific DNA-binding activity of several
      zinc-finger transcription factors, including estrogen receptor (ER) binding to
      its cognate estrogen response element (ERE). The mechanism accounting for this
      disruption of protein-DNA interaction is unknown, although polyamine induction of
      DNA conformational changes has been suggested. To determine if polyamines can
      directly impair ER action, we compared the effects of putrescine (Putr),
      spermidine (Spd), and spermine (Spm) on ER DNA-binding (ER-ERE complex
      formation), ER ligand-binding (estradiol), ER structure (circular dichroism and
      sucrose gradient sedimentation), and the capacity of ER to transactivate an ERE
      tk-CAT reporter in transient transfection assays. Polyamine concentrations
      causing 50% inhibition of ER-ERE formation (IC50 values) were found to be 1 mM
      for Putr, 4 mM for Spd, and 3 mM for Spm. This loss of ER DNA-binding was
      associated with a direct and irreversible effect on the ER DNA-binding domain (ER
      DBD). Additionally, polyamines were observed to inhibit ER ligand-binding with
      IC50 values of 10 mM for Putr, 2 mM for Spd, and < 0.1 mM for Spm; and this
      correlated with a measureable change in higher-order ER structure (5S to 3.5S
      sedimentation) and inhibition of intracellular ER transactivation. These findings
      suggest that in ER-positive human breast tumors with increased polyamine
      (especially Spm) content, ER structure and function may be directly altered by
      tight-ion polyamine complexing that results in loss of ER-mediated gene
      regulation.

PMID- 9598872
TI  - Mutation screening of BRCA1 using PTT and LOH analysis at 17q21 in breast
      carcinomas from familial and non-familial cases.
AB  - Germline mutations in the BRCA1 gene predispose to breast and ovarian cancer. An
      estimated 45% of families with multiple breast cancer cases and more than 80% of
      breast-ovarian cancer families are linked to BRCA1. Mutation analyses by
      collaborative laboratories have revealed around 460 distinct BRCA1 sequence
      alterations, mostly germline mutations from familial cases. The majority of these
      alterations were nonsense and frame-shift mutations. In the present study, breast
      tumors of both sporadic and familial origin were investigated for allelic
      imbalance (AI) at the BRCA1 locus. AI was observed in 52% of the sporadic cases
      and in 17% of the familial cases. Furthermore, 104 breast carcinomas from
      patients with sporadic disease and 77 patients with positive family histories of
      breast and/or ovarian cancer were examined for translation-terminating mutations
      in exon 11 of the BRCA1 gene using the protein truncation test (PTT). No somatic
      mutations were detected in any of the tumors analysed, and only one BRCA1
      mutation carrier was found among the familial cases. The result of this study
      gives no indication that truncating somatic mutations in exon 11 of BRCA1 play a
      major role in the tumorigenesis of the breast. Furthermore, the frequency of such
      mutation carriers in breast cancer populations with weak family histories of
      breast and/or ovarian cancer seems to be low.

PMID- 9598873
TI  - Effect of retinoid analogues on mammary cancer in transgenic mice with c-neu
      breast cancer oncogene.
AB  - Breast cancer is one of the most common cancers and is a leading cause of
      mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast
      cancer oncogene under the control of an MMTV promoter and appears to be a useful
      animal model for evaluation of intervention strategies to delay/prevent breast
      cancer. Fiber-rich nonpurified diet (NTP-2000), as compared to a purified diet
      (AIN-76A), has previously been shown to significantly delay the development of
      mammary cancer in the TG.NK model. Four-week old hemizygous TG.NK female mice
      with MMTV/c-neu oncogene were fed NTP-2000 diet containing the retinoid analogue
      4-hydroxyphenyl retinamide (4-HPR) at 5 mM/kg or an arotinoid Ro 40-8757 at 2 and
      3 mmol/kg for 26 weeks. The 4-HPR at 5 mmol/kg diet delayed the development of
      palpable tumors up to 24 weeks, but by 26 weeks, the incidence was not
      significantly different from the NTP-2000 diet control group. However, the 4-HPR
      diet markedly decreased the average weight of the tumors at 26 weeks. The 4-HPR
      diet also caused a significant increase in body weight without an increase in
      food consumption. Arotinoid Ro-40-8757 at both doses inhibited the development of
      mammary tumors for the duration of the study. However, the Ro 40-8757 at 3
      mmol/kg appeared to be toxic as indicated by a significant depression of the
      average body weight with alopecia and skin scaling in some mice. Our observations
      with TG.NK transgenic mouse and fiber-rich diet (NTP-2000) indicate that the
      arotinoid Ro 40-8757 has a markedly higher inhibitory effect on the development
      of mammary cancer than 4-HPR. Studies to evaluate genetic changes and expression
      of hormonal receptors and growth factors associated with the inhibition of
      mammary cancer development by the retinoid analogues are in progress.

PMID- 9598874
TI  - Therapeutic potential of recombinant p53 overexpression in breast cancer cells
      expressing endogenous wild-type p53.
AB  - Reconstitution of the p53-dependent apoptotic pathway by gene transfer of a
      recombinant wild-type p53 minigene leads to rapid apoptotic cell death in breast
      and other cancer cell types expressing null or mutant p53. Tumour cells
      expressing wild-type p53 have been reported to be more resistant to this
      treatment strategy, presumably as a result of mutations in downstream regulators
      of p53-dependent apoptotic signalling. The MCF-7 breast cancer cell line is
      representative of this class of tumour cell. Our recent observation of a p53
      dependent apoptotic response following adenovirus-mediated HSV thymidine kinase
      gene transfer and gancyclovir treatment led us to reexamine recombinant p53
      cytotoxicity in MCF-7 cells. Infection with a recombinant adenovirus expressing
      wild-type p53 resulted in a dramatic increase in p53 protein levels and was
      accompanied by an increase in p21WAF/CIP1 protein levels and G1 arrest within 24
      hours post-infection. A significant decrease in MCF-7 cell viability was first
      observed at 5 days post-infection and coincided with the appearance of
      morphological and biochemical changes consistent with apoptotic cell death. By
      day 7 post-treatment, cell viability decreased to 45% and clonogenic survival was
      reduced to 12% of controls. The results demonstrate that persistent, high level
      expression of recombinant p53 can induce programmed cell death in MCF-7 cells.
      While the mechanism by which p53 overexpression overcomes the defect in
      downstream apoptotic signalling is not clear, our data suggests that this
      treatment strategy may be beneficial for the class of tumour cells represented by
      the MCF-7 cell line.

PMID- 9598875
TI  - The golem of osteoporosis genetics.

PMID- 9598876
TI  - Rheumatoid arthritis associated autoimmune systems.

PMID- 9598877
TI  - Immunoblotting detection of autoantibodies to human epidermis filaggrin: a new
      diagnostic test for rheumatoid arthritis.
AB  - OBJECTIVE: We previously reported that so-called antikeratin antibodies (AKA) and
      antiperinuclear factor (APF) recognize epitope(s) present on human epidermal
      filaggrin. In the present study, we developed a new diagnostic test for
      rheumatoid arthritis (RA) based on detection of antifilaggrin autoantibodies
      (AFA) by immunoblotting. METHODS: We tested 670 serum samples, including 190 RA.
      AFA titers were estimated by immunoblotting on filaggrin enriched human epidermis
      extracts, and AKA titers by indirect immunofluorescence (IIF) on rat esophagus
      epithelium. Diagnostic values of the tests were compared. RESULTS: Each test
      resulted in diagnosis of more than 40% of RA samples, with a specificity of 0.99.
      Although the tests were strongly correlated, their association allowed the
      diagnosis of more than 60% of RA samples, with the same specificity. CONCLUSION:
      Immunoblot detection of AFA, a simple and standardizable test, may be an
      alternative or complement to conventional IIF detection of AKA.

PMID- 9598878
TI  - Diagnostic value of antibodies to filaggrin in rheumatoid arthritis.
AB  - OBJECTIVE: To determine the prevalence of antibodies to filaggrin in a cross
      sectional sample of patients with rheumatoid arthritis (RA). METHODS: Filaggrin
      from human skin was either extracted with 0.05% Nonidet P-40 and then partially
      purified by precipitating in ethanol and resuspending in water (Nonidet
      preparation) or extracted with 9 M urea and then purified by sequential
      fractionation on a DEAE Sephadex column and on a strong cation exchange column
      (purified preparation). Antibodies to filaggrin were detected using
      immunoblotting techniques with sera diluted 1:50. Antikeratin antibodies (AKA)
      were detected using indirect immunofluorescence microscopy on sections of rat
      esophagus. RESULTS: Antibodies to filaggrin were detected in 5 of 30 sera of
      patients with RA using filaggrin from the Nonidet preparation and 6 of 49 sera
      using filaggrin from the purified preparation. AKA were detected in 13 of 40
      sera. A positive correlation existed between the presence of AKA and the presence
      of antibodies to filaggrin using the purified preparation (p=0.017). CONCLUSION:
      These data indicate that the reactivity of RA sera with filaggrin is not
      identical to the presence of AKA and is variable depending upon the preparation
      of filaggrin used. The diagnostic value of antibodies to filaggrin remains to be
      proven.

PMID- 9598879
TI  - Quantitative rheumatology: a survey of outcome measurement procedures in routine
      rheumatology outpatient practice in Canada.
AB  - OBJECTIVE: To assess the extent to which quantitative clinical measurement is
      performed by rheumatologists in the longitudinal followup of patients with
      rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and
      fibromyalgia (FM) in routine outpatient practice in Canada. METHODS: A cross
      sectional postal survey was conducted using an 18 item self-administered
      questionnaire sent to Canadian Rheumatology Association members. RESULTS:
      Rheumatologists (response rate 85%) were more likely to longitudinally follow
      patients with RA and AS than those with OA or FM. There was a high degree of
      variability in the methods used to monitor patients longitudinally. Many measures
      used in clinical research were used infrequently in routine clinical practice. In
      general, the major health status measures surveyed were not used in clinical
      monitoring. There was a high level of agreement (>80%) that the characteristics
      required of an outcome measure for use in clinical practice should include
      simplicity, brevity, ease of scoring, reliability, validity, and sensitivity to
      change. CONCLUSION: The majority of Canadian rheumatologists perform outcome
      measurement during the longitudinal followup of their outpatients with RA, AS,
      OA, and FM. However, the process lacks standardization. High performance health
      status measures, developed for clinical research, have not been widely adopted in
      rheumatology practices. There is agreement on the characteristics required by
      Canadian rheumatologists for measurement procedures used in routine clinical
      care. Quantitative measurement in clinical practice using standardized procedures
      is an attainable, but as yet, unrealized opportunity.

PMID- 9598880
TI  - Serum homocysteine and methylmalonic acid in patients with rheumatoid arthritis
      and cobalaminopenia.
AB  - OBJECTIVE: To analyze the significance of cobalaminopenia (< 200 pmol/l) in
      patients with severe rheumatoid arthritis (RA). METHODS: We studied 42 patients
      with RA and cobalaminopenia (incidence 4%). Most patients had severe and
      longstanding disease. Concentrations of homocysteine, methylmalonic acid (MMA),
      gastrin, and pepsinogen 1 were analyzed in sera that had been stored frozen. A
      capillary gas chromatographic mass spectrometric technique was used to determine
      homocysteine and MMA. RESULTS: As a group, patients had significantly higher
      levels of serum homocysteine and serum MMA than laboratory reference probands (p
      < 0.0001 and p < 0.005, respectively). Individually, 20 of 39 patients had
      elevated serum levels of homocysteine (> 15 micromol/l). In 12 of 39 patients
      serum levels of MMA were elevated (> 0.37 micromol/l). Twenty of 42 patients had
      biochemical signs of disturbed gastric function. CONCLUSION: Our findings were
      compatible with the hypothesis that cobalaminopenia is one of several biochemical
      signs of gastrointestinal dysfunction in patients with severe RA. It is suggested
      that the hyperhomocysteinemia associated with vitamin B12 deficiency, folate
      deficiency, vitamin B6 deficiency, and impaired renal function may have a role in
      promoting high cardiovascular morbidity in patients with RA.

PMID- 9598881
TI  - Effect of vitamin D receptor gene alleles on bone loss in early rheumatoid
      arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a polygenic disease characterized by
      localized joint destruction and generalized osteoporosis resulting in increased
      fracture risk. The pathogenetic mechanisms that determine the severity of
      generalized bone loss in RA are poorly understood. Polymorphisms in the vitamin D
      receptor (VDR) gene have been described as a significant determinant of bone
      turnover and mass. In this prospective study we describe VDR gene allele effects
      on bone loss in patients with early RA. METHODS: We recruited 232 patients with
      early RA. Bone mineral density measurements were repeated in 167 patients. Serial
      clinical and laboratory measures were recorded during the period of followup. DNA
      extraction, polymerase chain reaction amplification, and restriction fragment
      length polymorphism analysis of VDR alleles were performed using standard
      techniques. Presence of the Taq restriction site for both alleles was denoted
      "tt", and absence "TT". RESULTS: In women with RA the tt genotype group lost bone
      more rapidly than subjects with TT genotype at both the lumbar spine (-0.1 vs 
      4.9% p.a, respectively; p < 0.05) and femoral neck (-3.9 vs -9.6%, respectively;
      p < 0.01). The effect was independent of other disease characteristics.
      CONCLUSION: The presence of the VDR gene "t" allele in female patients with RA
      was associated with accelerated bone loss.

PMID- 9598882
TI  - Sense of coherence--a protective factor for depression in rheumatoid arthritis.
AB  - OBJECTIVE: A stress-vulnerability model of depression was investigated in
      patients with rheumatoid arthritis (RA). Antonovsky's Sense of Coherence (SOC)
      was examined as a factor protecting against depression. METHOD: Relationships
      between sociodemographic factors, disease activity, functional impairment, pain,
      depression, and SOC were assessed using multivariate methods in a cross sectional
      sample of 89 consecutive outpatients with RA. RESULTS: Increased prevalence of
      depression was associated with low SOC and high self-rated pain levels, but not
      with other factors assessed. By multiple regression analysis, independent
      contributions to depression were observed for SOC (23% of variance) and for pain
      (24% of variance), but not functional impairment or disease activity. CONCLUSION:
      Comprehensive models of adjustment in RA need to include protective factors such
      as SOC, in addition to pain and other pathological variables. SOC may be helpful
      in identifying individuals with RA who are particularly vulnerable to depression,
      who may be helped by focused psychological interventions such as cognitive
      therapy.

PMID- 9598883
TI  - Evaluation of a modified needle for small joint biopsies.
AB  - OBJECTIVE: To assess the value of a new short biopsy needle modified from the
      Parker-Pearson needle in obtaining adequate synovial tissue from small joints.
      METHODS: The short needle is 2.5 cm in length with a repositioned hooked biopsy
      notch closer to the end of the needle to allow better specimen retrieval. It can
      be used to obtain synovial biopsies from small joints of the hand using the usual
      arthrocentesis approaches. RESULTS: Ten patients underwent 12 synovial biopsies
      with a success rate of 92%. No complications from the procedure were observed.
      Samples obtained were adequate for a variety of studies including synovial
      histopathological evaluation, electron microscopy, and DNA extraction.
      CONCLUSION: The new modified short needle expands the spectrum of joints that can
      be biopsied for diagnostic and research purposes in an outpatient setting.

PMID- 9598884
TI  - The effect of a static wrist orthosis on hand function in individuals with
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine the effect of a wrist orthosis on work performance, hand
      dexterity, and pain during task performance, 40 individuals with rheumatoid
      arthritis were studied using a 2 period, crossover design. METHODS: Each patient
      was fitted with a Futuro wrist orthosis. Dexterity was measured with and without
      the orthosis using the Jebsen Hand Function Test. Work performance was assessed
      using 2 tasks (one simulating the use of shears, the other the use of a
      screwdriver) on a work simulator. All tasks were performed both with and without
      the orthosis, with the order of orthosis versus no orthosis randomly assigned.
      Pain before and after performing tasks was assessed using a 10 cm horizontal
      visual analog scale. RESULTS: While on the screwdriver task work performance was
      less with the orthosis (p = 0.0002); on the shears task there was no significant
      difference in work performance with and without the orthosis. The average pain
      after performing both tasks was significantly less with the orthosis on. A 2
      factor analysis of variance model with repeated measures suggested that taking
      into account the reduced work performance during splint wear, pain was still
      significantly reduced with splint wear. The average time to complete all 7 tasks
      on the Jebsen Hand Function Test was longer when the subjects wore the splint
      compared to when they did not (62.0 vs 57.6 s, respectively; p = 0.0086).
      CONCLUSION: The results suggest that the effect of splint wear on work
      performance is highly task specific, and thus the ergonomic demands of the
      individual's daily life must be considered if a splint is to provide maximal
      effectiveness.

PMID- 9598885
TI  - Clinical features and evolution of antinuclear antibody positive individuals in a
      rheumatology outpatient clinic.
AB  - OBJECTIVE: To identify individuals with antinuclear antibodies (ANA) not
      fulfilling criteria for systemic lupus erythematosus (SLE) or other connective
      tissue diseases (CTD); to describe their clinical and serological features, to
      identify factors indicating evolution to SLE. METHODS: A case-control study,
      based on retrospective evaluation of clinical files. The cases were ANA positive
      individuals (n = 50) examined in a medical outpatient setting, for symptoms
      compatible with SLE, but not fulfilling SLE classification criteria. Two patients
      with SLE were matched to each case in terms of age at initial symptom onset and
      sex. Thyroid autoimmunity was assessed by detecting antithyroid antibodies.
      Fisher's exact test and conditional logistic regression were used to evaluate the
      predictive ability of initial findings for SLE development. RESULTS: ANA positive
      individuals suspected of having a CTD present a wide variety of symptoms and
      findings, usually at the 4th to 5th decade of life. Antibodies to Sm and U1RNP
      were absent; anti-Ro(SSA) and anti-La(SSB) occurred in 6%, while anti-dsDNA
      occurred in less than 10% of the cases. Arthritis, butterfly and discoid rash,
      Raynaud's phenomenon, and anti-Ro/SSA antibodies are the initial findings
      indicating evolution to SLE. Hematological abnormalities such as leukopenia and
      thrombocytopenia as well as constitutional symptoms such as easy fatigue and
      arthralgias are not associated with evolution to SLE. Antithyroid antibodies were
      detected in 16% of the cases and 2.3% of controls. CONCLUSION: ANA may connote a
      form of systemic autoimmunity that is expressed as a wide variety of complaints,
      even in the absence of a definite diagnosis of CTD. Arthritis, rash, Raynaud's
      phenomenon, and anti-Ro/SSA antibodies indicate evolution to SLE. Autoimmune
      thyroid disease occurs in ANA positive individuals not fulfilling SLE
      classification criteria rather than in patients with SLE.

PMID- 9598886
TI  - Fatigue in lupus is not correlated with disease activity.
AB  - OBJECTIVE: The relationship between fatigue and disease activity in systemic
      lupus erythematosus (SLE) has been questioned. We examined whether self-reported
      fatigue in patients with SLE is correlated with disease activity. METHODS:
      Consecutive patients with SLE at the University of Toronto Lupus Clinic were
      evaluated for disease activity using the Systemic Lupus Erythematosus Disease
      Activity Index (SLEDAI). They were also evaluated for fibromyalgia (FM) by
      American College of Rheumatology criteria. One hundred patients completed the
      following health status questionnaires: the Fatigue Severity Score (FSS), Center
      for Epidemiologic Studies Depression Scale (CES-D), and Medical Outcomes Study
      Short Form Health Survey (SF-20). Disease activity was measured by the SLEDAI.
      Statistical correlations were made using the Spearman test. RESULTS: No
      significant correlation was found between FSS scores and SLEDAI (p = NS). Fatigue
      was found to be highly correlated with the presence of FM (p < 0.05) and
      depression (p < 0.01). In addition, fatigue was significantly associated with
      lower performance in all 6 domains of the SF-20 (p < 0.001); disease activity
      correlated with decreases in social function, mental health, and health
      perception areas of the SF-20. SLEDAI was not found to correlate with FM (p =
      NS). CONCLUSION: Fatigue in patients with SLE does not correlate with disease
      activity. However, fatigue is correlated with FM, depression, and lower overall
      health status in this population. Fatigue is a manifestation of these conditions,
      which are commonly co-expressed in SLE, and may reflect a decreased overall
      coping ability in these patients, rather than active disease itself.

PMID- 9598887
TI  - A double blind placebo controlled trial of azathioprine in the treatment of
      primary Sjogren's syndrome.
AB  - OBJECTIVE: To establish whether there is a place for low dose azathioprine (AZA)
      as a disease modifying agent in patients with uncomplicated primary Sjogren's
      syndrome (SS). METHODS: Twenty-five patients with primary SS were entered into a
      double blind, placebo controlled trial of AZA (1 mg/kg/day) for a period of 6
      months. RESULTS: Six patients, all receiving active drug, withdrew because of
      side effects. There was no significant change in disease activity variables when
      measured clinically, serologically, or histologically. CONCLUSION: This trial
      suggests that low dose AZA does not have a role as a disease modifying agent in
      SS.

PMID- 9598889
TI  - Oral manifestations in patients with Sjogren's syndrome.
AB  - OBJECTIVE: To investigate oral signs and symptoms in patients with Sjogren's
      syndrome (SS), and to compare results with a group of healthy individuals.
      METHODS. Each individual completed a questionnaire designed to investigate
      his/her perception of oral health and dryness, as well as a list of signs and
      symptoms associated with xerostomia. An oral clinical evaluation was performed.
      RESULTS: A total of 81 subjects were studied, 21 with primary SS, 29 with
      secondary SS, and 31 healthy individuals. Patients with SS considered that their
      oral health was poor. Oral dryness was perceived as intense. Symptoms most
      commonly expressed were: sensitivity to acids (68%), difficulty eating dry foods
      (66%), and sensitivity to spicy foods (58%). Dryness of the lips (76%) and the
      tongue (68%) were also among the most frequent complaints. Oral findings of
      patients with SS included cervical or atypical caries in 83%, fissured
      erythematous tongue in 70%, and oral candidiasis in 74%. Significant differences
      were found when results obtained from patients with SS were compared with the
      healthy group. CONCLUSION: The oral health of this group of patients with SS was
      deficient. Adequate management of dry mouth was not achieved, mainly for the
      modifiable components such as dental decay and oral candidiasis. Therefore.
      treatment and prevention plans are mandatory. These measures might help to reduce
      the discomfort associated with oral dryness and to reduce dental loss.

PMID- 9598888
TI  - Primary Sjogren's syndrome: role of the HLA-DRB1*0301-*1501 heterozygotes.
AB  - OBJECTIVE: To examine the respective role of the DRB1*, DQB1*, and DPB1* HLA
      alleles in primary Sjogren's syndrome (SS) and in the clinical and autoantibody
      profile of primary SS. METHODS: HLA-DRB1*, DQB1*, and DPB1* alleles were analyzed
      in 42 patients with primary SS and 200 controls by reverse dot blot hybridization
      for DRB1* and DPB1* and by polymerase chain reaction-restriction fragment length
      polymorphism for DQB1*. RESULTS: We found a significant increase of the HLA
      DRB1*15-*03 heterozygote genotype frequency (19% primary SS vs 3.5% controls;
      p<0.0006, OR=6.49) and especially for the HLA-DRBI*1501-*0301 genotype (16.7%
      primary SS vs 3% controls; p<0.002, OR=6.47). The DQB1*0201-*0602 genotype was
      also significantly increased in primary SS (17.1% primary SS vs 4% controls;
      p<0.006, OR=4.86). However, the higher risk to primary SS development was
      associated with the DRB1*1501-*0301 genotype (OR=6.47 vs 4.86). There were no
      differences between patients and controls in DPB1* allele frequencies. The HLA
      DRB1*15-*03 heterozygote genotype was also associated with systemic features such
      as hematologic manifestations and Raynaud's phenomenon (RP) and with autoantibody
      production such as antinuclear, anti-Ro(SSA) or La(SSB) autoantibodies and
      rheumatoid factor. CONCLUSION: Our data suggest a role of the HLA-DRB1*1501-*0301
      heterozygote genotype in susceptibility to primary SS. Moreover, the HLA
      DRB1*1501-*0301 genotype was also found to be associated with a particular form
      of the disease characterized by RP, hematologic manifestations, and autoantibody
      production.

PMID- 9598890
TI  - Oral candidiasis and Sjogren's syndrome.
AB  - OBJECTIVE: To determine the prevalence of oral candidiasis (OC) in patients with
      Sjogren's syndrome (SS), to identify oral signs and symptoms associated with OC,
      and to compare them with a healthy group. METHODS: Patients with primary SS, and
      with SS associated with autoimmune disease were identified according to
      established criteria. Each individual had: (1) a questionnaire, (2) an oral
      clinical evaluation, (3) a set of microbiological tests: tongue smear, culture of
      tongue smear, and saliva sample. Diagnosis of OC was established with 2 positive
      results and the presence of any sign or symptom. RESULTS: A total of 81 subjects
      were studied, 21 with primary SS, 29 secondary SS, and 31 healthy subjects. We
      diagnosed OC in 74% of patients with SS, which was statistically significant
      compared to the healthy group (23%) p < 0.001. Frequent symptoms associated with
      OC were increased sensitivity to spicy foods (58%) and unpleasant metallic taste
      (40%). Common signs of OC were erythematous lesion on the dorsum of the tongue
      (68%) and angular cheilitis (24%). CONCLUSION: Prevalence of OC was high in
      patients with SS. The frequency of signs and symptoms associated with OC may
      explain some of the clinical manifestations. If chronic erythematous OC is found
      in patients with SS an oral assessment at every appointment may help provide
      appropriate treatment.

PMID- 9598891
TI  - Familial Mediterranean fever clinical and genetic features in Druzes and in Iraqi
      Jews: a preliminary study.
AB  - OBJECTIVE: A number of differences have been noted in clinical familial
      Mediterranean fever (FMF) among ethnic groups. Iraqi Jews and Druzes are
      characterized by less severe disease. The differences in disease expression raise
      the possibility of background genes peculiar to specific ethnic groups. METHODS:
      We analyzed a series of FMF linked microsatellite markers and searched for gene
      mutations in these 2 populations. RESULTS: We observed a conserved haplotype in
      46% of the FMF druze chromosomes that was different from the Mediterranean
      haplotype but identical to the ARM3 haplotype. In contrast, 56% of the FMF
      chromosomes in Iraqi Jews displayed the same mutation as that found in Jews from
      North Africa. CONCLUSION: Variable expression in FMF is probably due to both
      allelic heterogeneity and/or modifier genes as well as environmental factors.

PMID- 9598892
TI  - Cutaneous vasculitis in a defined population--clinical and epidemiological
      associations.
AB  - OBJECTIVE: To examine the value of the American College of Rheumatology (ACR)
      1990 criteria for Henoch-Schonlein purpura (HSP) and hypersensitivity vasculitis
      (HSV) and the Chapel Hill Consensus Conference (CHCC) definition of cutaneous
      leukocytoclastic angiitis (CLA) in the classification of cutaneous vasculitis and
      to estimate the annual incidence of biopsy proven cutaneous vasculitis in a well
      defined population. METHODS: ACR criteria for HSP and HSV and the CHCC definition
      for CLA and HSP were applied to an unselected cohort of 84 patients with biopsy
      proven cutaneous vasculitis attending a single district hospital in the United
      Kingdom between January 1990 and December 1994. RESULTS: Thirty-seven patients
      fulfilled ACR criteria for HSV, of whom 27 also fulfilled the ACR criteria for
      HSP. Thirty-two patients met the CHCC definition for CLA and 7 the CHCC
      definition for HSP. The overall annual incidence of cutaneous vasculitis was
      38.6/million (95% CI 30.6-48.1), and for CLA 15.4/million (95% CI 10.6-21.8).
      CONCLUSION: The ACR 1990 criteria for HSP and HSV overlap; the CHCC definitions
      for CLA and HSP provide clearer distinction. Cutaneous vasculitis is as common as
      systemic vasculitis.

PMID- 9598893
TI  - Hepatitis G and hepatitis C RNA viruses coexisting in cryoglobulinemia.
AB  - OBJECTIVE: Hepatitis G virus (HGV) has been identified as a new member of the
      Flaviridae family, which includes the hepatitis C virus (HCV). There is a well
      established association between HCV and cryoglobulinemia; however, to date HGV
      has not been linked with various types of cryoglobulinemia. We investigated the
      association of HGV with cryoglobulinemia. METHODS: We studied 10 patients with
      cryoglobulinemia. The cryoglobulins were purified and identified by
      immunofixation electrophoresis. HGV and HCV RNA were studied in the serum and in
      purified cryoglobulins by reverse transcriptase polymerase chain reaction.
      RESULTS: Nine of 10 patients were women, aged 37-74 years. These patients had
      combinations of hepatitis C (6), vasculitis (7), lymphoproliferative (3), and
      autoimmune and connective tissue diseases (3). Of the 10 patients, 3 were
      positive for both HGV RNA and HCV RNA. Two of three patients with dual infection
      of HGV and HCV had malignancies (Waldenstrom's macroglobulinemia, B cell
      lymphoma). In one of these 3 patients HGV RNA was positive in the cryoglobulin
      fraction, but not in serum. Three other patients were positive for HCV RNA alone.
      CONCLUSION: HGV may be associated with cryoglobulins. Our three patients were co
      infected with HCV. Since our series is small, the pathogenetic role of hepatitis
      G and its relationship to malignancy remain to be elucidated.

PMID- 9598894
TI  - Bone mineral density and biochemical markers of bone metabolism in ankylosing
      spondylitis.
AB  - OBJECTIVE: To determine (1) bone mineral density (BMD) of the axial and
      appendicular skeleton in men with moderate and severe ankylosing spondylitis
      (AS), and (2) associations between BMD and bone metabolism variables. METHODS:
      Nineteen men with AS and 19 healthy male controls were evaluated for osteoporosis
      by dual energy x-ray absorptiometry in both the hip and the lateral and posterior
      anterior (PA) projections of the lumbar spine. Calcium homeostasis was evaluated
      by measuring minerals, calcitropic hormones, and markers of remodeling. Total
      testosterone levels were also measured. RESULTS: Osteopenia was noted in both the
      hip and spine of the subjects with AS. The lateral projection of L3 was a more
      sensitive indicator of the vertebral BMD compared to the PA projection. Calciuin
      homeostasis and testosterone levels were normal in subjects with AS. In most
      subjects, markers of bone formation and resorption were normal. CONCLUSION: BMD
      of subjects with AS is decreased, in spite of normal calcium homeostasis and bone
      remodeling indices.

PMID- 9598895
TI  - Prolonged and increasing expression of Fos related antigens in the hippocampus of
      adjuvant arthritic rats.
AB  - OBJECTIVE: To study the influence of chronic arthritis on induction of Fos
      related antigens in the brain. METHODS: We studied 3 different experimental rat
      groups: rats with adjuvant induced arthritis (AR), paraffin oil (vehicle)
      injected rats (VR), and normal control rats (NCR). At 2, 4, and 6 days after and
      2.4, 8, 12, and 18 weeks after inoculation, sections from the hippocampus were
      immunostained with antibodies against c-Fos and other Fos related antigens (FRA).
      Immunostained neurons in CA1, CA2, CA3, and dentate gyrus were counted and their
      expression pattern was studied. To relate the expression of FRA to the
      upregulation of an opioid peptide, leucine-enkephalin (Leu-enk), double
      immunohistochemistry for FRA and Leu-enk was performed. RESULTS: Brain samples of
      the NCR group exhibited very few FRA immunoreactive cells. All the 4 regions of
      AR and VR hippocampus had upregulated FRA expression in very early stages of
      arthritis induction. Hippocampus of the VR rats showed generally diminished FRA
      expression in later stages of arthritis. Hippocampus of the AR rats, in contrast,
      showed increased FRA expression in the later stages. This increased expression of
      FRA topographically and chronologically coincided with upregulation of Leu-enk.
      CONCLUSION: Longterm arthritis presumably caused prolonged and increased
      expression of FRA. Increased expression of Leu-enk, which temporally and
      spatially colocalized with FRA, may represent longterm genomic changes that occur
      in patients with rheumatoid arthritis.

PMID- 9598896
TI  - Intraarticular tissue proliferation after immobility: methods of assessment and
      preliminary results in rat knee joints.
AB  - OBJECTIVE: To develop methods to quantify intraarticular connective tissue
      proliferation after immobility and to report results in an animal model of joint
      contracture. METHODS: Six rats had their right knee joints immobilized with an
      internal fixator for 3 weeks. The joints were harvested and sectioned. We
      measured the length of synovial intima and the subintimal area with image
      analysis software. Proliferating synoviocytes were identified by
      immunohistochemistry using the "proliferating cell nuclear antigen" antibody and
      were counted under optical microscopy on whole joint sections. Two outcomes were
      analyzed: the subintimal area and a synoviocyte proliferation index (number of
      proliferating synoviocytes/synovial intima length). Both were obtained for
      posterior and anterior aspects of the knee. RESULTS: Intra and interobserver
      reliabilities over 87% were found with these measurement techniques. Subintimal
      area means were not statistically different between immobilized and contralateral
      knees. In all subjects, the synoviocyte proliferation index (SPI) posteriorly was
      higher in immobilized than in contralateral knees (p<0.05), due to an increase in
      proliferating cells (p<0.05) rather than a change in synovial intima length
      (p>0.05). The SPI anteriorly was comparable in immobilized and contralateral
      knees (p>0.05). CONCLUSION: We developed methods to measure intraarticular
      connective tissue proliferation in a contracture model in vivo. Proliferative
      changes in the posterior aspect of the knee suggest local mediation of connective
      tissue proliferation in the contracture process. These methods and preliminary
      results will benefit investigators assessing interventions in similar models.

PMID- 9598898
TI  - Prevalence of radiographic hip and knee osteoarthritis by place of residence.
AB  - OBJECTIVE: To determine the associations between place of residence and sex
      specific prevalence rates of radiographic hip and knee osteoarthritis (OA).
      METHODS: We used data from the first National Health and Nutrition Examination
      Survey (NHANES I), 1971-1975, to calculate and compare sex-specific prevalence
      rates for radiographic hip and knee OA in urban and rural areas; standard
      metropolitan statistical areas (SMSAs) and non-SMSAs; other urban-rural subtypes
      that we defined; and major geographic regions of the United States. We used
      logistic regression to estimate crude and adjusted odds ratios for the
      associations between place of residence and radiographic hip and knee OA.
      RESULTS: We found no significant differences in the prevalence rates of hip or
      knee OA by place of residence for either men or women. After adjusting for age,
      race, and body mass index, we found a nonsignificant 40-50% increase in the odds
      of radiographic hip OA among men living in rural areas and non-SMSAs; no such
      increase was seen among women. No increased odds of knee OA were noted for
      subjects of either sex living in rural areas or non-SMSAs. CONCLUSION: In the
      NHANES I population, rural and non-SMSAs residence may be modestly associated
      with radiographic hip OA for men. Place of residence does not appear to be
      associated with radiographic hip OA among women or with radiographic knee OA in
      either sex.

PMID- 9598897
TI  - The effects of tenidap on canine experimental osteoarthritis: II. Study of the
      expression of collagenase-1 and interleukin 1beta by in situ hybridization.
AB  - OBJECTIVE: To examine the effect of tenidap on the expression of collagenase- and
      interleukin 1beta (IL-1beta) genes in experimental canine osteoarthritis (OA).
      METHODS: The anterior cruciate ligaments of the right stifle joints of
      experimental dogs were sectioned by a stab wound incision and tissues samples
      were taken. Four dogs had received no treatment, 4 were treated with oral
      omeprazole (20 mg/day), and another 4 were treated with tenidap (3 mg/kg/bid) and
      omeprazole (20 mg/day). The dogs received medication for 8 weeks; all dogs were
      sacrificed at the end of this period. Tissues from 4 healthy dogs were used as
      controls. IL-1beta and collagenase-1 gene expression were measured in synovial
      membrane (synovial lining cells and mononuclear cell infiltrate) and collagenase
      1 expression in cartilage using in situ hybridization techniques. Results were
      calculated as the percentage of cells expressing the gene, and expressed as cell
      score. RESULTS: The collagenase-1 cell score in the full thickness samples was
      significantly higher in OA cartilage than in normal cartilage, both in condyles
      and plateaus (p < 0.0002). Tenidap treated dogs showed a significantly lower cell
      score in femoral condyles and tibial plateaus in the superficial (p < 0.0002),
      deep (p < 0.005, p < 0.002, respectively), and full thickness (p < 0.0002) layers
      compared to OA dogs. No staining for collagenase-1 was observed in normal
      membrane. In OA synovial membrane, the collagenase-1 cell score was high in both
      the synovial lining cells and mononuclear cell infiltrate. Tenidap treated dogs
      showed a significantly lower score compared to OA tissue in both the synovial
      lining cells (p < 0.03) and the mononuclear cell infiltrate (p < 0.03). The
      relative decrease in the collagenase-1 cell score in the tenidap treated dogs was
      more pronounced in the mononuclear cell infiltrate. Staining for IL-1beta was
      observed in only a few lining cells in normal synovial membrane from unoperated
      dogs. In OA synovial membrane from untreated dogs, staining for IL-1beta was
      intense and was found in all dog specimens. The cell score was significantly
      higher in OA lining cells (p < 0.03) and mononuclear cell infiltrate (p < 0.03)
      compared to normal. In tenidap treated dogs, the score for IL-1beta was
      significantly lower than in OA, both in synovial lining cells (p < 0.03) and
      mononuclear cell infiltrate (p < 0.03). CONCLUSION: Tenidap significantly reduced
      in vivo expression of collagenase-1 and IL-1beta in experimental OA. These data
      are an extension of our previous study and showed that tenidap exerts its
      protective effects on OA lesions, likely by reducing the catabolic pathways of
      the disease.

PMID- 9598899
TI  - The effect of thalidomide and 2 analogs on collagen induced arthritis.
AB  - OBJECTIVE: Thalidomide has been described as an inhibitor of both angiogenesis
      (which may account for its teratogenic effects on limb bud formation) and tumor
      necrosis factor-alpha (TNF-alpha) production. We evaluated its therapeutic
      potential in collagen induced arthritis (CIA), a rat model of rheumatoid
      arthritis (RA). METHODS: Rats were administered orally 200 mg/kg/day thalidomide
      (n = 10) or either of 2 analogs, EM-12 (n = 9) or supidimide (n = 9). An
      additional group was given thalidomide (n = 10) at 200 mg/kg twice daily, and a
      control group (n = 13) was given vehicle only. At completion of the protocols,
      serum levels of TNF-alpha and vascular endothelial growth factor (VEGF) were
      measured. RESULTS: Suppression of inflammatory synovitis by clinical and
      radiographic criteria was significantly lower in all experimental protocols
      except the lower dose thalidomide group. The EM-12 analog was the most
      efficacious, and twice daily thalidomide was better than once daily. The
      incidence of arthritis onset was comparable among all groups. Strong cell
      mediated and humoral responses to type II collagen, measured by a radiometric
      delayed type hypersensitivity assay and anti-type II collagen IgG ELISA,
      respectively, were similar in the experimental and control groups. TNF-alpha and
      VEGF levels were increased in all rats immunized with collagen compared to naive
      controls. CONCLUSION: Thalidomide and its analogs can suppress the clinical
      severity of rat CIA, but the mechanism of action is not a result of TNF-alpha or
      VEGF downregulation.

PMID- 9598900
TI  - Calcific tendinitis in the posterior proximal thigh as a self-limited condition:
      pathogenic role of inflammatory responses.
AB  - OBJECTIVE: Calcific tendinitis occurs rarely in the posterior proximal thigh. We
      investigated whether it is self-limited and how the natural course of the disease
      progresses. METHODS: We treated 6 patients with no surgical intervention, and
      analyzed laboratory and radiological findings in the followup period of more than
      one year (average followup, 2.5 yrs). RESULTS: Although tendinitis was severe,
      rapid relief was observed within 2 weeks (average 5 days). Radiological features
      including extraskeletal calcifications did not change within 2 weeks, and then
      improved by 6 weeks. Four of 6 cases showed abnormal laboratory variables. All
      elevated white blood cell counts and C-reactive protein levels improved within
      one week with clinical resolution. In comparison with time course of the
      symptoms, changes in the radiological findings over time appeared not to be
      parallel with the clinical course, but laboratory progression appeared to
      correspond well with clinical resolution. CONCLUSION: Inflammatory responses to
      hydroxyapatite crystals may play a role in the pathogenesis of symptoms of
      calcific tendinitis in the posterior proximal thigh, most of which are self
      limited.

PMID- 9598901
TI  - Functional sites of chemically modified tetracyclines: inhibition of the
      oxidative activation of human neutrophil and chicken osteoclast pro-matrix
      metalloproteinases.
AB  - OBJECTIVE: We studied the relative ability of 6 different chemically modified non
      antimicrobial analogs of tetracycline (CMT) to inhibit human and chicken matrix
      metalloproteinases (MMP) in vitro. The ability of tetracycline and its analogs to
      inhibit MMP appears to depend on the Ca++/Zn++ binding site at C11 (carbonyl
      oxygen) and C12 (OH group) of the molecule, which is lacking in CMT-5, the
      pyrazole derivative of tetracycline. This significant property of CMT-5 was used
      to differentiate between the effects of CMT on already active MMP versus the
      oxidative activation of latent MMP (pro-MMP). METHODS: Cultured chicken
      osteoclast conditioned medium and purified human neutrophil progelatinase (MMP-9)
      and pro-collagenase (MMP-8) were assayed for proteinase activities using gelatin
      and collagen, respectively. The pro-MMP were activated either by preincubation
      with 1 mM aminophenylmercuric acetate (APMA) or 100 microM sodium hypochlorite
      (NaOCI). CMT were added either to the preincubation mixtures together with NaOCl
      or after activation of pro-MMP with NaOCl. RESULTS: All CMT tested, except CMT-5,
      inhibited APMA or NaOCl activated pro-MMP. However, CMT-5 (like the other CMT),
      inhibited the oxidative activation of pro-MMP by NaOCl when added together by
      scavenging the reactive oxygen species. The degradation of type-I collagen by
      chicken osteoclast conditioned medium was probably due to MMP-2 and/or MMP-13.
      CONCLUSION: Oxidative activation of pro-MMP may be crucial during soft
      tissue/bone destruction in the inflammatory diseases, including the arthritides.
      Our results indicate that the Ca++/Zn++ binding site of CMT is not essential for
      inhibition of the oxidative activation of pro-MMP.

PMID- 9598902
TI  - Aspects of use of antimalarials in systemic lupus erythematosus.

PMID- 9598903
TI  - Estimates of the discriminant ability of definitions of improvement for juvenile
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the ability of various definitions of improvement to
      distinguish between patients with juvenile rheumatoid arthritis (JRA) treated
      with active drug from those given placebo in randomized trials. METHODS: A core
      set of 6 response (outcome) variables for use in JRA has been reported. These
      core variables were combined into a number of "definitions of improvement" for
      the purpose of classifying individual patients as either "clinically
      significantly improved" or "not improved." We used a large dataset from
      randomized controlled trials to test the discriminant ability (sensitivity to
      change) of the definitions. We calculated the proportion of patients classified
      as "improved" by each definition in each of the treatment and control groups.
      RESULTS: Effect sizes were weak in 4 of the treatment regimens used (D
      penicillamine, hydroxychloroquine, auranofin, and very low dose methotrexate) and
      no definition discriminated well between drug and placebo treated groups.
      Definitions that required 20 to 30% improvement in 3 to 4 of the 6 core set
      variables showed statistically significant differences in the proportions of
      patients who were classified as improved in the group treated with low dose
      methotrexate (10 mg/m2 body surface area/wk) compared to placebo. A definition
      resembling the Paulus criteria used in adult RA trials (4 of 6 core set variables
      improved by > or = 20%) performed well, as did the definition selected previously
      as the best for JRA (3 of 6 core set variables improved by > or = 30%, not more
      than one worsening by > 30%). CONCLUSION: Definitions that require 20 to 30%
      improvement in 3 to 4 core outcome variables are sensitive to change and are able
      to clearly distinguish between treated and control groups when an effective drug
      is being tested. Further testing of their validity is under way.

PMID- 9598904
TI  - Bone mineral density and turnover in children with systemic juvenile chronic
      arthritis.
AB  - OBJECTIVE: To assess bone mineral status in a group of children with systemic
      type juvenile chronic arthritis (JCA), which places them at high risk to develop
      osteoporosis. METHODS: Bone mineral density (BMD) was measured in 17 children
      aged 6-18 yrs (mean 14.9 +/- 4.5) with systemic JCA and in 18 matched controls by
      dual energy x-ray absorptiometry. Bone turnover was determined by quantitative
      bone scintigraphy, using quantitative single photon emission computed tomography
      based on skeletal uptake of methylene diphosphonates (MDP uptake). Serum
      concentrations of minerals, osteocalcin, and bone alkaline phosphatase were
      determined. Nutrient intake was assessed by a 24 hour dietary recall. RESULTS:
      Patients with systemic JCA who received corticosteroid therapy had significantly
      reduced BMD in both the lumbar spine (p < 0.05) and the femoral neck (p < 0.05)
      compared to controls, whereas BMD values of the non-steroid systemic JCA patients
      were not different from controls. Bone turnover measurement by MDP uptake showed
      no difference between patients with JCA and controls. Levels of calcium,
      phosphorus, alkaline phosphatase. and osteocalcin were within normal limits in
      all patients. CONCLUSION: Patients with systemic JCA receiving longterm steroid
      treatment may develop a significant decrease in BMD. The normal MDP uptake values
      together with normal osteocalcin levels that we observed in our patients indicate
      that their disease is not associated with enhancement of bone turnover rates.
      These observations might have therapeutic implications for prevention and
      management of osteoporosis in JCA.

PMID- 9598905
TI  - Hypercalciuria and hematuria in juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the frequency of hypercalciuria and the relationship
      between hypercalciuria and hematuria in patients with juvenile rheumatoid
      arthritis (JRA). METHODS: Twenty-eight children with JRA were studied, as well as
      10 patients with acute arthritis unrelated to JRA and 14 healthy children as
      control groups. Cases with urinary calcium excretion (UCE) >4 mg/kg/day were
      considered hypercalciuric. Urinalysis was performed for detecting hematuria in
      all cases. RESULTS: UCE was 4.19 +/- 2.9 mg/kg/day in patients with JRA, 1.94 +/-
      1.57 mg/kg/day in children with acute arthritis, and 2.0 +/- 1.45 mg/kg/day in
      healthy children. UCE was significantly higher in JRA compared with the other
      study groups. Of the 28 patients with JRA, 13 (46.4%) had hypercalciuria and 6
      (21.4%) had hematuria. UCE was significantly higher in hematuric patients with
      JRA than in those with no hematuria (p<0.05). UCE in patients with JRA without
      hematuria was also higher than the UCE values detected in the disease and healthy
      control groups (p<0.05). CONCLUSION: Hypercalciuria is a frequent finding in
      patients with JRA [13/28 (46.4%)] and should be considered during the
      investigation of hematuria in patients with JRA.

PMID- 9598906
TI  - Thermography and nailfold capillaroscopy as noninvasive measures of circulation
      in children with Raynaud's phenomenon.
AB  - OBJECTIVE: To determine in a pilot study the feasibility of noninvasive
      techniques of (a) measurement of rewarming response after a standard cold
      challenge test (using thermographic imaging) and (b) measurement of nailfold
      capillary dimensions using video capillaroscopy, in the assessment of children
      presenting with Raynaud's phenomenon (RP). METHODS: Ten children with RP and 10
      age matched healthy controls were studied. No child had definite evidence of
      underlying connective tissue disease. RESULTS: Children with RP had abnormal
      rewarming curves. The gradient of the rewarming curve was significantly lower in
      children with RP (median 1.5 vs 5.0 degrees C/min in controls; p = 0.015), and
      there was a trend for the lag time (the interval between the end of the cold
      challenge and the onset of rewarming) to be increased in children with RP (median
      4.7 vs 0.5 min in controls; p = 0.08). Capillary dimensions were measured in 7 of
      the children with RP, and were similar to those of healthy controls. CONCLUSION:
      Thermography and nailfold capillaroscopy are feasible in children and should be
      further evaluated.

PMID- 9598907
TI  - Immunogenetic studies in families of children with juvenile dermatomyositis.
AB  - OBJECTIVE: We reported an association between juvenile dermatomyositis (JDMS) and
      the HLA-DQA1*0501 allele. The purpose of this study was to determine whether
      there is evidence for linkage between JDMS and the DQA1*0501 allele in JDMS
      families. METHODS: The study population included 18 unrelated patients with JDMS,
      their parents, and 49 unaffected siblings. Using molecular genetic techniques, we
      studied the HLA genes, DRB1, DQA1, and tumor necrosis factor-alpha. RESULTS:
      Using the transmission disequilibrium test, we confirmed our earlier observations
      that the HLA-DQA1*0501 allele confers primary susceptibility to JDMS. CONCLUSION:
      DQA1*0501 confers genetic risk for JDMS; we cannot exclude the effects of alleles
      at other linked loci that were not studied or interactive effects between DQA1
      alleles and alleles at other loci.

PMID- 9598908
TI  - Hypermobility among Egyptian children: prevalence and features.
AB  - OBJECTIVE: To determine the prevalence, clinical manifestations, and possible
      associated features of hypermobility among Egyptian children in a prospective
      study. METHODS: Nine hundred ninety-seven healthy children from 4 different
      educational areas for primary and presecondary schools were screened for the
      presence of hypermobility. A hypermobility score was used to denote the degree of
      laxity. Sites and possible clinical associations of hypermobility were
      determined. RESULTS: The presence of hypermobility was 16. 1% among Egyptian
      children. Hypermobility was more frequent among girls (18%). than boys (14.4%),
      although the difference was not statistically significant. Age was inversely
      correlated with the frequency of hypermobility (r = 4).967, p < 0.001) and degree
      of joint laxity (r = -0.789, p < 0.01). Hypermobility was most prevalent in
      fingers (96.9%) and least prevalent in knee joints (3.1%). Hypermobility was
      statistically more frequent in nondominant than dominant fingers (p < 0.002).
      Arthralgia, high palate, flat feet, Raynaud's phenomenon, and easy bruising were
      more common among the hypermobility group. CONCLUSION: Our results suggest that
      hypermobility is not uncommon among Egyptian children. Increased awareness of the
      condition is needed among pediatricians and other concerned physicians.

PMID- 9598909
TI  - Exudative pleural effusion and pleural leukocytoclastic vasculitis in limited
      scleroderma.
AB  - Involvement of the lung in scleroderma is common, but pleural effusion and
      vasculitis are rarely reported in scleroderma. We describe a 43-year-old woman
      with limited scleroderma who developed an exudative pleural effusion associated
      with pleural leukocytoclastic vasculitis.

PMID- 9598910
TI  - Meningeal involvement in Wegener's granulomatosis.
AB  - We describe a rare neurological manifestation of Wegener's granulomatosis,
      meningeal involvement, which occurred despite therapy resulting in disease
      quiescence in other organs. Clinical, radiographic, and neuropathological
      features are described.

PMID- 9598911
TI  - Prolonged response of multicentric reticulohistiocytosis to low dose
      methotrexate.
AB  - We describe a case of multicentric reticulohistiocytosis complicated by central
      retinal vein thrombosis and trigeminal neuropathy. A variety of treatment
      modalities were tried in this patient. Both skin disease and arthritis responded
      to low dose methotrexate over 8 years of followup. Graduated compression gloves
      produced an excellent cosmetic improvement in the disfiguring skin lesions.

PMID- 9598912
TI  - Mycobacterium xenopi arthritis.
AB  - Osteoarticular Mycobacterium xenopi infections are very rare. We describe a
      patient with dermatomyositis and isolated shoulder arthritis due to M. xenopi.
      The diagnosis was delayed for 7 months; only 2 of 5 interval joint aspirates grew
      M. xenopi. The infection responded well to triple antituberculous therapy.

PMID- 9598913
TI  - Polyarticular blastomycotic arthritis.
AB  - Blastomycotic arthritis usually presents as acute monoarticular septic arthritis
      resembling a bacterial process. Only 2 cases in the literature have subsequently
      developed arthritis in a second joint. We describe the case of an elderly woman
      with polyarticular blastomycotic arthritis associated with lung, skin, and bone
      involvement. The organism was identified in the synovial fluid and skin biopsies.
      Our patient underwent open drainage and aspiration of the involved joints and
      received antimycotic therapy.

PMID- 9598914
TI  - The fibromyalgia problem.

PMID- 9598915
TI  - The fibromyalgia problem.

PMID- 9598916
TI  - The fibromyalgia problem.

PMID- 9598917
TI  - The fibromyalgia problem.

PMID- 9598918
TI  - The fibromyalgia problem.

PMID- 9598919
TI  - The fibromyalgia problem.

PMID- 9598920
TI  - The fibromyalgia problem.

PMID- 9598921
TI  - The fibromyalgia problem.

PMID- 9598922
TI  - The fibromyalgia problem.

PMID- 9598923
TI  - Hydroxychloroquine ocular toxicity.

PMID- 9598924
TI  - Joint hypermobility and musculoskeletal pain.

PMID- 9598925
TI  - Dramatic response to intravenous high dose gamma-globulin in refractory
      vasculitis of the skin associated with Sjogren's syndrome.

PMID- 9598926
TI  - Production of cytokines in patients infected by hepatitis C virus.
AB  - T helper type 1 (Th1) cytokines play an important role in antiviral defence. The
      purpose of this study was to quantify by ELISA IL2, soluble receptor of IL2
      (IL2Rs), IFNgamma TNFbeta, IL4, IL6 and IL10 levels in the sera of 134 HCV
      positive patients, 69 of whom were coinfected with HIV, and in 54 HIV-HCV
      negative patients. The mean IL2Rs and IFN serum levels were much higher in
      patients with anti-HCV than in the control group, whereas the mean IL4 and IL6
      levels were lower in patients infected with HCV. There were no significant
      differences in cytokine levels between patients with and without HIV. There were
      significantly less patients with HCV than controls with IFNgamma levels under cut
      off, and significantly more patients with HCV with IL4 levels under cut-off.
      Although serum level of cytokines must be interpreted with caution, the results
      suggest that Th1 response is enhanced in HCV infection.

PMID- 9598927
TI  - Evidence for high genetic diversity and long-term endemicity of hepatitis C virus
      genotypes 1 and 2 in West Africa.
AB  - During 1994 and 1995, the prevalence of hepatitis C virus (HCV) and its genotypes
      were studied in several rural and urban populations in three West African
      countries: Guinea, Burkina Faso, and Benin. The following groups were screened
      for antibodies to HCV (anti-HCV): 459 villagers in the forest region of Guinea;
      965 individuals in urban, suburban, and rural populations of the Bobo Dioulasso
      area, Burkina Faso; and 582 blood donors in Cotonou, Benin. In Benin, 60 patients
      with sickle cell anemia (30 with and 30 without history of multiple transfusion)
      and 13 hospital patients with liver disease were also tested. RT-PCR detection of
      HCV-RNA was carried out on all anti-HCV positive samples, followed by genotyping
      and sequencing of unrecognized subtypes. The prevalence rates of anti-HCV were
      1.1% in the Guinean population group, 1.4% among blood donors in Benin, and 4.9%
      in residents of Burkina Faso. In patients with sickle cell anemia, five of the 30
      polytranfused patients (17%) had anti-HCV, whereas none of the patients without a
      history of blood transfusion had anti-HCV (P < 0.05). Among the 13 patients with
      liver disease, five had anti-HCV, of whom four had history of blood transfusion.
      HCV-RNA was detected in 41 anti-HCV positive sera. All belonged to genotypes 1 or
      2, with a high genomic diversity; 18 different subtypes were identified,
      including 2c, 2d, and 16 new subtypes. Such genetic diversity poses a challenge
      for vaccine development and also implies that HCV infection is long-established
      in these West African regions.

PMID- 9598928
TI  - GBV-C/HGV infection in chronic hepatitis C patients: its effect on clinical
      features and interferon therapy.
AB  - A novel virus (GBV-C/HGV) may be associated with some liver diseases including
      fulminant hepatitis and acute and chronic hepatitis. On the other hand, many
      investigations showed that this infection does not contribute to liver disease.
      GBV-C/HGV has been found to occur in association with infection with other
      hepatitis viruses. We investigated the effect of GBV-C/HGV infection on the
      clinical features and interferon treatment in patients with chronic hepatitis C.
      A total of 262 hepatitis C virus (HCV) RNA positive patients with chronic
      hepatitis were examined in this study. The detection of serum GBV-C/HGV RNA was
      done by RT-PCR using specific primers from the NS5 regions. Interferon-alpha was
      given at a dose of 6 MU/day for 16 or 24 weeks. A responder was defined as a
      patient with ALT normalization and HCV RNA disappearance after treatment. GBV
      C/HGV RNA was detected in 28 (11%) patients. No significant difference was
      detected in clinical features (age, sex, liver-related biochemical tests, and
      histological examination) between the 28 GBV-C/HGV-positive patients and the GBV
      C/HGV-negative patients. Using interferon therapy for hepatitis C, the responder
      rates of GBV-C/HGV-positive and -negative patients were 14% and 20%,
      respectively. Of the 28 patients with GBV-C/HGV RNA, GBV-C/HGV RNA was tested
      after interferon therapy in 16 and of these GBV-C/HGV RNA was not detected in
      nine patients after therapy. These findings suggest that GBV-C/HGV infection dose
      not affect the clinical features in patients with HCV and the efficacy of
      interferon therapy for chronic hepatitis C.

PMID- 9598929
TI  - GB virus C prevalence in blood donors and high risk groups for parenterally
      transmitted agents from Gauteng, South Africa.
AB  - The prevalence of GBV-C infection in voluntary blood donors and in groups at high
      risk for parenteral exposure to infectious agents was studied. The high risk
      groups included chronic renal failure patients on haemodialysis, renal transplant
      patients and haemophiliacs from Gauteng. The presence of GBV-C RNA in these
      populations was determined using reverse transcription polymerase chain reaction
      (RT-PCR) in the 5' non-coding region (NCR) of the virus. Of the blood donors,
      11.1% (95% CI 7.6, 15.8) were positive, whereas 23.8% (95% CI 12.6, 40.2) of
      haemodialysis patients and 23.5% (95% CI 15.9, 33.3) of the haemophiliacs were
      infected with GBV-C. The highest proportion of infection was in the renal
      transplant patients, where 41.2% (95% CI 35.1, 47.7) were found to have
      circulating GBV-C RNA. Serological markers for hepatitis B (HBV) and hepatitis C
      viruses (HCV) were also measured as indicators of other hepatitis viruses with
      important parenteral transmission routes. Of the GBV-C positive blood donors,
      3.6% were also HBsAg positive and none were positive for HCV. The GBV-C positive
      patients on haemodialysis were not positive for either HBsAg or antibodies to
      HCV, but had evidence of past infection with HBV since 40% were anti-HBc
      positive. The greatest proportion of HCV positives was in the haemophiliac group,
      91.3%, none of these were HBsAg positive but 39.1% had anti-HBc. In the GBV-C
      positive renal transplant patients, 4% had HBsAg, 13.3% had anti-HBc and 2.1% had
      antibodies to HCV. This is the first report describing the prevalence of GBV-C in
      South African populations.

PMID- 9598931
TI  - Molecular analysis of GB virus C isolates in Belgian hemodialysis patients.
AB  - GB virus C (GBV-C) has been detected in Belgian hemodialysis patients. To study
      their genomic diversity and phylogenetic relationship, a 592 nucleotide fragment
      extending from the 5' non-coding region to part of the E1 gene of the GBV-C
      genome was amplified and sequenced from 12 Belgian hemodialysis patients in two
      different centers. Together with strains from different geographical origins,
      these sequences were analyzed phylogenetically using three different methods. A
      consistent tree topology was obtained with all methods. Three GBV-C genotypes
      were observed with two subtypes in type 2 and a questionable subtyping in type 1.
      Except for one isolate falling into type 1 cluster which mainly consists of
      African strains, all the other Belgian strains clustered within the type 2a
      branch. Two GBV-C isolates in two patients from the same hemodialysis center
      clustered together closely, suggesting a nosocomial transmission. In view of
      their long branch length, it seems unlikely that the other Belgian strains
      evolved recently from a common ancestor. Our results indicate that the major type
      circulating among Belgian hemodialysis patients seems to be 2a, which is usual
      for Europe and North America, but that the African type 1 also exists to a minor
      extent. Although patient to patient transmission of GBV-C in Belgian hemodialysis
      centers did occur, it may not account for the majority of infections.

PMID- 9598930
TI  - Heterogeneity in E2 region of GBV-C/hepatitis G virus and hepatitis C virus.
AB  - GB virus C/hepatitis G virus (GBV-C/HGV) is related distantly to hepatitis C
      virus (HCV). HCV has a hypervariable region (HVR), and exists as quasispecies in
      vivo. Although GBV-C/HGV also has replaceable amino acids in the presumed
      antigenic region, the existence and fluctuation of population of heterogeneous
      virus have not been evaluated. In this study, the heterogeneity of GBV-C/HGV and
      HCV was investigated by the single-strand conformation polymorphism (SSCP)
      analysis in six concomitantly infected patients. Two patients were observed for 4
      years without any treatment, and four were treated with interferon-alpha (IFN).
      By SSCP analysis, amplicons of GBV-C/HGV RNA were separated into 1-5 bands on
      gels for each patient. The amplicons had different nucleotide but the same amino
      acid sequences in the presumed antigenic region. The amplicons of HCV RNA,
      separated into 1-4 bands, had different nucleotide and amino acid sequences in
      the HVR. In the two patients without treatment, the predominant strain of GBV
      C/HGV was unchanged for the 4 years. In the four patients administered IFN, some
      strains of GBV-C/HGV disappeared after IFN therapy, whereas other strains
      persisted. The mean genetic distance among GBV-C/HGV strains represented by SSCP
      analysis was significantly lower than that of HCV (P < 0.05). The data indicate
      that: 1) GBV-C/HGV can be devoid of antigenic drift unlike HCV; 2) GBV-C/HGV has
      no HVR as seen in HCV in the presumed antigenic region; and 3) the sensitivity to
      IFN differs among GBV-C/HGV strains in the same hosts, as with HCV.

PMID- 9598932
TI  - Infection with GB virus C, hepatitis C and B viruses in 1,044 cases autopsied at
      the Medical Examiner's Office in Tokyo.
AB  - Markers of GB virus C (GBV-C), hepatitis C virus (HCV) and hepatitis B virus
      (HBV) were sought in sera from 1,044 cases autopsied at the Medical Examiner's
      Office, Tokyo Metropolitan Government. GBV-C RNA was detected in 35 (3%) cases at
      a frequency significantly higher (P < 0.05) than in blood donors in Tokyo (4 of
      448 or 1%). Three genotypes of GBV-C provisionally designated G1, G2 and G3 were
      determined by selective amplification with type-specific primers, and G3 (Asian
      type) was detected in 31 (89%), G2 (European/American type represented by the
      prototype hepatitis G virus) in three (9%) and G1 (West African type represented
      by the prototype GBV-C) in one (3%). Antibody to HCV (anti-HCV) was detected in
      116 (11%) cases and accompanied by HCV RNA in 88. HCV genotypes were I/1a in one
      (1%), II/1b in 55 (63%), III/2a in 17 (19%) and IV/2b in 13 (15%). Antibodies to
      hepatitis B virus (HBV) was detected in 335 (32%) cases and hepatitis B surface
      antigen in 14 (1%). Subtypes were determined in 12 of them, adw was found in
      seven (58%), adr in four (33%) and adyr in one (8%). GBV-C RNA was detected
      significantly more frequently (P< 0.01) in the cases with liver disease (9 of 70
      or 13%) than in those with the other causes of death (26 of 974 or 3%). Anti-HCV
      was more frequent in the cases with GBV-C RNA than in those without it (15 of 35
      or 43% vs. 101 of 1,009 or 10%, P< 0.001). These results indicate that infection
      with GBV-C as well as HCV was common, while infection with HBV was not common in
      the Medical Examiner's autopsy cases in Tokyo.

PMID- 9598933
TI  - Lack of anti-GOR antibody among subjects with GB virus C/hepatitis G virus RNA.
AB  - Homologies were sought between the putative amino acid sequences of GB virus
      C/hepatitis G virus (GBV-C/HGV) and the GOR epitope or the liver/kidney microsome
      1 (LKM-1) epitope, which share partial sequence identity with the hepatitis C
      virus (HCV) polyprotein. Anti-GOR antibody (anti-GOR) was assayed among 100
      subjects with GBV-C/HGV RNA. Twenty-one and 25 subjects were coinfected with
      hepatitis B virus (HBV) or HCV, respectively. Homologies were found between the
      NS5 or E2 polyproteins of GBV-C/HGV and the GOR epitope or the LKM-1 epitope,
      respectively. These segments of GBV-C/HGV polyproteins sharing identity with the
      GOR or the LKM-1 epitope were well conserved among three genotypes of GBV-C/HGV.
      However, only 1 of 55 subjects (1.8%) with GBV-C/HGV RNA, but not with HBV or
      HCV, was positive for anti-GOR. The positivity for anti-GOR among the group with
      GBV-C/HGV RNA alone was significantly lower than that among the groups with HCV
      RNA (P < 0.01 and P < 0.05, respectively). Only 2 of 55 subjects (3.6%) with GBV
      C/HGV RNA alone exhibited elevation of alanine aminotransferase. The incidence of
      liver dysfunction among the group with GBV-C/HGV RNA alone was significantly
      lower than the incidence among the groups with GBV-C/HGV RNA and hepatitis B
      surface antigen (HBsAg) or HCV RNA (P< 0.01 and P< 0.01, respectively). These
      data indicate that 1) there is no association between GBV-C/HGV infection and the
      presence of anti-GOR, and 2) GBV-C/HGV infection is not related to chronic liver
      dysfunction.

PMID- 9598935
TI  - Quantitative differences in the distribution of zidovudine resistance mutations
      in multiple post-mortem tissues from AIDS patients.
AB  - Replication of HIV introduces errors into the genome which are responsible for
      conferring a growth advantage over wildtype virus when drugs such as zidovudine
      (ZDV) exert a selective pressure. The molecular basis for HIV-1 resistance to ZDV
      has been mapped to codons 41, 67, 70, 215 and 219 of the reverse transcriptase
      gene both in vitro and in clinical samples of blood. This study has investigated
      the relationship between the quantitative prevalence of ZDV resistance in
      multiple organs of the same individual. Proviral HIV-1 load was measured by
      quantitative-competitive PCR in 90 samples from organs of 11 patients dying with
      AIDS. Nine of these patients had been prescribed zidovudine. The distribution of
      wildtype and mutant sequences at the positions 41, 67, 70, 215 and 219 of the
      reverse transcriptase was assessed using a point mutation assay. The results
      showed that the highest proviral loads were predominately found in lymph node,
      spleen and lung and there was a significant association between viral load and
      resistance to ZDV (P=0.008). Inter-organ distribution of wildtype and mutant
      sequences at codons 41, 67, 70, 215 and 219 was frequently not uniform and in
      some patients differed markedly between the lymphoreticular system and other
      organs. These results demonstrate that treatment of HIV-1 infection with
      zidovudine does not exert uniform selective pressures in multiple organs. These
      findings have implications for the interpretation of resistance data and design
      of treatment strategies for HIV, arguing in particular that alterations in
      therapeutic regimens should consider the likelihood of different resistance
      patterns being present in multiple sites within the same individual.

PMID- 9598934
TI  - Comparison of tests for antibody to hepatitis E virus.
AB  - The results of serologic tests for hepatitis E virus have varied widely from
      laboratory to laboratory, making interpretation of seroepidemiologic studies
      difficult. The present study compares serologic results with different antigens
      and tests developed in two laboratories for their ability to diagnose hepatitis E
      and measure antibody prevalence in a high risk population in Saudi Arabia. The
      results confirm that tests based upon open reading frame (ORF) 3 of HEV are of
      limited value for seroepidemiologic studies, whereas ORF2-based antigens have
      broad utility and yield data that are reproducible in more than one laboratory.

PMID- 9598936
TI  - A survey for 32 nucleotide deletion in the CCR-5 chemokine receptor gene
      (deltaccr-5) conferring resistance to human immunodeficiency virus type 1 in
      different ethnic groups and in chimpanzees.
AB  - The 32 nucleotide deletion in the CCR-5 chemokine receptor gene referred to as
      deltaccr-5 has been shown to confer resistance to HIV-1. Using PCR, 1,105 human
      subjects and 33 common chimpanzees were genotyped attributing them to one of the
      three possible genotypes: wild-type homozygote (w/w); deltaccr-5 homozygote
      (deltaccr-5/deltaccr-5) and deltaccr-5/wild-type heterozygotes (deltaccr-5/w).
      The ethnic groups investigated included different Middle Eastern nationalities
      (mainly Arab) and Russians. Carriers of the deltaccr-5 mutation were found among
      Arabs, Iranians and Russians. The highest frequency of the mutation was seen in
      Russians (24.4% of the deltaccr-5 heterozygotes, allele frequency-0.1221).
      Surprisingly, the only deltaccr-5 homozygote identified in our study was an
      Egyptian. The origin of the deltaccr-5 mutation in the Middle Eastern
      populations, both Arab and non-Arab, is most probably due to a gene flow from the
      Europeans. The frequency of the deltaccr-5 mutation in Russians is one of the
      highest known. It might be one of the factors contributing to a relatively slow
      pace of increase in the incidence of sexually acquired HIV infection in Russia.
      None of the chimpanzees tested was positive for deltaccr-5. Interestingly, the
      DNA sequence of the chimpanzee CCR-5 gene in the region including the site of the
      deltaccr-5 mutation, and flanking areas, was virtually identical to the
      homologous human sequence, only two mismatches (silent substitutions) were found.

PMID- 9598937
TI  - HTLV-Is in Argentina are phylogenetically similar to those of other South
      American countries, but different from HTLV-Is in Africa.
AB  - To understand the origin and past dissemination of human T-cell
      leukemia/lymphotropic virus type I (HTLV-I) in Latin America, we conducted a
      phylogenetic study of five new HTLV-I isolates from Argentina. We sequenced
      partial fragments of long terminal repeats (LTR) of the new HTLV-Is, and then the
      sequences were subjected to a phylogenetic analysis for comparison with other
      HTLV-Is of various geographical origins. Our results indicated that all the
      isolates were members of the Cosmopolitan group. Furthermore, most (four out of
      five isolates) of the new HTLV-Is belonged to the Transcontinental (A) subgroup,
      the most widespread subgroup of the four subgroups in the Cosmopolitan group. In
      this subgroup, they were closely related to HTLV-Is found in other South American
      countries including those of Amerindians, and were different from those found in
      Africa. In contrast, the remaining one HTLV-I (ARGMF) did not show any clear
      similarity to known HTLV-I isolates belonging to the Cosmopolitan group. The
      close similarity of South American HTLV-Is strongly suggests a common origin of
      the virus in this continent. Our results do not support the proposed idea of
      recent introduction of HTLV-I into South America as a consequence of the slave
      trade from Africa, where phylogenetically different HTLV-Is predominate.

PMID- 9598938
TI  - Manganese superoxide dismutase (MnSOD) and autoantibodies against MnSOD in acute
      viral infections.
AB  - Sera of 146 patients with acute EBV, HAV, HBV, CMV, HSV, and rubella virus
      infections, and sera from 35 healthy controls were tested for the antioxidant
      enzyme manganese superoxide dismutase (MnSOD). An enzyme immunoassay that detects
      all isomeres of the enzyme was developed. The mean MnSOD value of healthy
      controls was 107 ng/ml. In HAV, HBV and EBV infections characterized by viral
      replication in internal organs, there was an average 5-fold rise of serum MnSOD,
      whereas in viral infections with low direct cytopathogenity, such as rubella, CMV
      and HSV, the MnSOD levels showed only minor rises. These sera were also tested
      for autoantibodies against MnSOD using a novel sensitive indirect enzyme
      immunoassay. The average IgM anti-MnSOD concentration in sera of healthy controls
      was 112 GU. In sera of patients with acute HBV, CMV, HSV or rubella virus
      infections IgM anti-MnSOD values were only slightly raised above the cut-off
      level. In contrast, in some patients with acute EBV infections anti-MnSOD
      concentrations rose up to 20-fold of normal values. In HAV infections the same
      phenomenon was observed in patients who had reactivated EBV infections. These
      findings indicate that EBV may facilitate the B-cell response to MnSOD. These
      autoantibodies may inhibit the protective function of MnSOD and prolong the
      disease by oxygen injury. Our concept on the pathogenic effect of the
      autoantibodies against MnSOD emphasizes the importance of the antioxidant enzyme
      in viral infections.

PMID- 9598939
TI  - Serological and genomic characterization of human rotaviruses detected in China.
AB  - A total of 1,385 stool specimens were collected from children with diarrhea at
      two hospitals in Wuhan, Hubei Province, China, in 1994 and 1995, and screened for
      rotavirus by polyacrylamide gel electrophoresis of viral RNA. Group A rotavirus
      was detected with high frequency; 56.5% (87/154) and 40.8% (502/1,231) of the
      specimens collected in 1994 and 1995, respectively, were positive for rotavirus.
      Assignment of G serotype and P type (VP4 genotype) of group A rotavirus by ELISA
      with monoclonal antibodies and/or PCR, respectively, showed that strains of G2
      P[4] and G1-P[8] specificity were predominant in 1994 and in 1995, respectively.
      In contrast, a single strain was found to have a P[9] type specificity, and no G4
      strain was detected. Unusual combinations of RNA pattern-subgroup-G serotype-P
      type, such as long pattern-subgroup I-G1-P[8], short pattern-subgroup II-G3-P[4]
      and short pattern-subgroup I-G1-P[4], were detected in four specimens. Nucleotide
      sequences of the VP8* and/or NSP5 genes from two Chinese P[8] strains 470 and 582
      and one Chinese P[9] strain 512 as well as five Japanese P[9] strains (K8, AU1,
      M318, 0264, and 0265) were determined and compared with the published sequences
      of the corresponding gene. In the phylogenetic tree of VP8* sequences of P[9]
      strains, which formed two clusters each having strain K8 or AU-1 as the
      representative strain, the Chinese P[9] strain was found in the cluster
      represented by AU-1, although it was most distantly related to other strains.
      While NSP5 sequences of human strains with P[9] specificity were related to
      simian and bovine strains, that of Chinese P[8] strains was most closely related
      to those of porcine strains. A single group C rotavirus (No. 208) was detected.
      Nucleotide sequences of its VP4, VP6, VP7, and NSP4 genes were very similar to
      those of group C human rotaviruses detected worldwide.

PMID- 9598940
TI  - A comparison of PCR with virus isolation and direct antigen detection for
      diagnosis and typing of genital herpes.
AB  - Patients attending the genitourinary medicine clinic at Watford General Hospital,
      UK, were examined for clinical signs of genital herpes infection. Genital swabs
      were taken from 194 patients (126 female, 68 male) who presented with genital
      ulceration or symptoms which were suggestive of genital herpes infection. Swabs
      from these patients were tested by three methods: (i) Detection of herpes simplex
      virus (HSV) antigen by direct HSV enzyme immunoassay (EIA), (ii) HSV isolation in
      Vero cell culture and (iii) HSV polymerase chain reaction (PCR). HSV was detected
      in 76 patients (39%) by EIA, in 93 (48%) by isolation in cell culture, and in 115
      (59%) by PCR. Isolation by cell culture has been considered as the "gold
      standard" for the detection of HSV in genital lesions, but in this study HSV PCR
      was significantly more sensitive. Comparison of the three methods was as follows:
      Cell culture vs. PCR: Sensitivity 93/115 (80.9%), Specificity 79/79 (100%). HSV
      EIA vs. PCR: Sensitivity 75/115 (65.2%), Specificity 78/79 (98.7%). HSV EIA vs.
      Cell culture: Sensitivity 75/93 (80.7%), Specificity 100/101 (99%). EIA was less
      effective in detecting HSV among recurrent than among first episode infections,
      in comparison to culture or HSV PCR. This is the first comparison of HSV PCR with
      two other routine diagnostic methods for confirming genital herpes infection in a
      symptomatic population. The infecting HSV type was identified by restriction
      digestion of 108 HSV amplicons: HSV-1:37/108 (34%), HSV-2:71/108 (66%). In this
      population HSV-1 causes a significant proportion of genital herpes cases, and HSV
      1 genital infection was detected in significantly more first episode infections
      (40.3%) than among recurrent infections (22.2%).

PMID- 9598941
TI  - Assessment of women with urinary incontinence.

PMID- 9598942
TI  - The effect of vitamin C and E on placental lipid peroxidation and antioxidative
      enzymes in perfused placenta.
AB  - BACKGROUND: To investigate placental lipid peroxidation products and
      antioxidative enzymes after vitamin C and/or E infusions into the maternal
      circulation of normal and preeclamptic placentas perfused in vitro. METHODS:
      Placentas from 29 normal and six preeclamptic women delivered between 27 and 41
      weeks of gestation were used in the study. RESULTS: Neither vitamin C (500
      microM) nor vitamin E (50 microM) had any effect on placental lipid peroxidation
      or antioxidative enzymes in normal placentas. Vitamin C infused in preeclamptic
      placentas decreased peroxidation potential, as an indicator of lipid peroxidation
      to the same level it was in normal placentas (812 vs. 649 mV/mgprot; p=0.420).
      The activity of superoxide dismutase (SOD) was lower (1350 vs. 2030 ng/mgprot;
      p=0.023) in preeclamptic placentas, and the activities of glutathione peroxidase
      (0.22 vs. 0.08 micromol/min x mgprot; p=0.010) and glutathione-S-transferase
      (19.8 vs. 13.1 micromol/min x mgprot; p=0.016) were higher in preeclamptic
      compared to normal placentas. CONCLUSION: In this study, based on in vitro
      perfused normal and preeclamptic placentas, exogenous antioxidative vitamins had
      no effect on lipid peroxidation or endogenous antioxidative enzymes in normal
      placenta, but reduced placental lipid peroxidation and could potentiate the
      activity of some endogenous placental antioxidative enzymes in preeclamptic
      placenta.

PMID- 9598943
TI  - The effect of L-arginine and pentoxifylline on postoperative adhesion formation.
AB  - BACKGROUND: Postoperative intraperitoneal adhesion formation is a major cause of
      infertility, pain, intestinal obstruction, and subsequent intraoperative
      complication. We investigated the effects of L-arginine and pentoxifylline for
      preventing postoperative adhesion in rats. METHODS: Forty Sprague-Dawley rats
      were subjected to a standardized lesion by serosal trauma of the uterine horn and
      parietal peritoneal defect. The agents were administered intraperitoneally at the
      end of surgery. The rats were assigned randomly into control (saline treated), L
      arginine, pentoxifylline and L-arginine with pentoxifylline groups. Two weeks
      after surgery, a second laparotomy was performed and the extent of adhesion
      formation was determined. The data were analyzed by Mann Whitney U test. RESULTS:
      In L-arginine and pentoxifylline administered groups, adhesion formation scores
      were significantly lower than the control group (p<0.05). However, the efficacy
      of L-arginine used together with pentoxifylline is not superior to those of L
      arginine or pentoxifylline alone. CONCLUSION: This study showed that L-arginine
      and pentoxifylline administered at the end of surgery reduced adhesion formation.

PMID- 9598944
TI  - Second trimester serum free beta human chorionic gonadotrophin levels as a
      predictor of pre-eclampsia.
AB  - BACKGROUND: To prospectively assess maternal serum free beta human chorionic
      gonadotrophin (beta hCG) estimation between 15 and 18 weeks gestation, as a
      screening test for pre-eclampsia in primigravid women. METHODS: A prospective
      longitudinal study in a University Teaching Hospital. The study population was
      430 primigravid women, who had maternal serum free beta hCG levels measured as
      part of antenatal serum screening for Down's Syndrome in the second trimester,
      who booked consecutively within the unit and went on to deliver on the unit's
      labor ward. These women were followed during their subsequent pregnancy and
      categorized into those who remained normotensive and those who developed pre
      eclampsia on both clinical and biochemical grounds. The beta hCG levels were used
      to construct a receiver operator characteristics curve (ROC) to assess the
      screening potential for pre-eclampsia. RESULTS: Nineteen (4.4%) women in the
      study group developed pre-eclampsia. The median second trimester free beta hCG
      multiples of the median (MOM) was significantly elevated compared to that of the
      control group (1.52 vs 1.10, p=0.03). The ROC curve shows that for a sensitivity
      of 79%, the specificity was only 54%. CONCLUSIONS: Maternal serum free beta hCG
      alone measured in the second trimester is not clinically useful as a screening
      test for pre-eclampsia in primigravid women. It has, however, some predictive
      value.

PMID- 9598945
TI  - Resistance index of uterine artery and placental location in intrauterine growth
      retardation.
AB  - BACKGROUND: Our aim was to investigate the relationship between placental
      location and resistance index (RI) of uterine arteries in cases with intrauterine
      growth retardation (IUGR). METHODS: Placental location and flow velocity
      waveforms of uterine arteries in 86 normal and 20 IUGR cases from 33 to 38 weeks
      of gestation were examined using a combined real-time scanner and pulsed Doppler
      ultrasonography. The location of placenta was classified as lateral when most of
      it was located to either the right or the left side of the uterine midline.
      Otherwise it was called central. Cases where the placenta was located in the
      uterine fundus or in the lower segment were not included. RI values were
      calculated from the uterine arteries on the placental side, on the non-placental
      side and in case of central placentas as a mean of both uterine arteries. In
      normal cases, the calculations were done every second week from 33 to 38 weeks of
      gestation, and the difference in variance among three gestational ages in each
      artery was tested by a one-way ANOVA. In IUGR cases, a standard deviation score
      (SDS) was calculated individually in each artery as (RI - normal mean)/normal SD.
      Differences in SDS between three categories of uterine arteries were examined by
      non-parametric tests. RESULTS: In normal cases, there was no significant
      difference in variance of RIs among three gestational ages in each category of
      arteries. In IUGR cases, SDSs on the placental side were higher than those on the
      non-placental side and those in central placenta, (p<0.01, Wilcoxon's and Mann
      Whitney's tests, respectively). SDSs in five of eight cases with central
      placentas were below 1.0. Two of 12 cases with lateral placentas had higher SDSs
      on the non-placental side than on the placental side and resulted in abruptio
      placentae. CONCLUSIONS: Deviation of RIs in uterine arteries with IUGR could be
      affected by the pathologic conditions of the utero-placental blood flow on the
      placental side of lateral placenta rather than in central placenta and might be
      done by dramatic increase in resistance to flow of the myometrial vessels on the
      non-placental side.

PMID- 9598946
TI  - Risk factors and morbidity in patients with placenta previa accreta compared to
      placenta previa non-accreta.
AB  - BACKGROUND: Placenta accreta is associated with high morbidity and most cases
      occur with placenta previa. This study was carried out in an attempt to define
      risk factors for placenta accreta in cases of placenta previa and to quantify the
      increased morbidity of placenta previa accreta in comparison to placenta previa
      alone. METHODS: The records of all patients delivered by cesarean section (CS)
      for placenta previa and accreta during the seven-year period from 1990 to 1996,
      inclusive, were reviewed. Data regarding the demographic features, previous CS,
      the incidence of hysterectomy and postpartum morbidity were analyzed. RESULTS:
      Out of 23070 deliveries 110 (0.48%) had placenta previa, twelve (0.05%) of whom
      had placenta previa accreta. There was no significant difference in age and
      parity. Patients with a history of previous CS showed a significant increase in
      the incidence of placenta previa accreta (p=0.001). The percentage of accreta
      increased linearly from 4.1% in patients with no CS to 60% in patients who had
      had three or more CS. Postpartum hemorrhage and emergency hysterectomy were
      significantly higher among the previa accreta patients compared with the previa
      patients alone (p<0.001; p<0.001, respectively). CONCLUSION: In the presence of a
      previous history of CS, patients with antepartum diagnosis of placenta previa are
      considered to be at a greater risk for having placenta accreta. The risk
      increases with the increase in the number of previous CS. Patients with placenta
      previa accreta have a significantly higher incidence of PPH and are more likely
      to undergo emergency hysterectomy.

PMID- 9598947
TI  - Nutritional stress of reproduction. A cohort study over two consecutive
      pregnancies.
AB  - BACKGROUND: The evaluation of nutritional stresses of reproduction is far more
      complex than perceived in the literature so far. The use of inappropriate outcome
      measures, the lack of adjustment for the complex inter-relationships among
      confounding variables, and the poverty of analytical models, has led to
      conflicting results. Our objective was to evaluate, using a new analytical
      framework, the maternal and fetal effects of the nutritional stress imposed by
      reproduction in a cohort of 278 women followed over two consecutive pregnancies.
      METHODS: The analytical framework evaluated nutritional stress over successive
      pregnancies. The effect of birth interval on change in maternal weight, body mass
      index and hemoglobin over two consecutive pregnancies was evaluated using
      multiple linear regression accounting for the effects of maternal age, parity and
      weight or body mass index or hemoglobin in the first of the two pregnancies. For
      change in fetal birth weight correction was made for the confounding effect of
      maternal age, parity and weight, and fetal gestational age, sex and birth weight.
      RESULTS: Birth interval was associated with change in maternal weight (p=0.001);
      change in body mass index (p=0.002); and change in birth weight (p=0.048). No
      association was found between birth interval and change in hemoglobin.
      CONCLUSIONS: The nutritional stress imposed by reproduction affects maternal and
      fetal outcomes. Maternal nutrient stores can be depleted and fetal growth can be
      restricted in association with shorter birth intervals. Perinatal nutrition may
      be improved by adequate spacing of pregnancies with appropriate birth control.

PMID- 9598949
TI  - The occurrence of breech presentation in Norway 1967-1994.
AB  - BACKGROUND: To study the occurrence of breech presentation and its association
      with demographic and geographic variables. METHOD: Population based cohort study
      from the Medical Birth Registry of Norway comprising all singleton deliveries
      1967-1994, a total of 1,592,064 deliveries. Of these, 45,921 in breech
      presentation. RESULTS: From 1967 through 1994, the breech presentation proportion
      increased from 2.2% (95% CI 2.1-2.3) to 3.4% (95% CI 3.2-3.5). Breech
      presentation was associated with high maternal age and low birth order, as well
      as low gestational age and birthweight. The secular trend was mainly due to
      demographic changes in terms of increasing proportions of births with low birth
      order and high maternal age. Breech presentation was most frequent in urban
      areas. CONCLUSIONS: Strong associations were observed between breech presentation
      and low birth order as well as high maternal age. The findings are compatible
      with both intrinsic as well as environmental mechanisms. A full understanding of
      the birth order effect necessitates further studies based on sibship data.
      Prevention of premature delivery would be an effective measure for reducing the
      breech presentation proportion.

PMID- 9598950
TI  - Factors influencing delivery method in breech presentation.
AB  - BACKGROUND: To study factors influencing delivery method in breech presentation.
      METHODS: Population based cohort study from The Medical Birth Registry of Norway,
      comprising all singleton deliveries in Norway, 1967-1994, 1,592,064 deliveries of
      which 45,921 (2.9%) were in breech presentation. RESULTS: The proportion of
      cesarean section in breech presentation increased from 3.6 per 100 in 1969 to
      58.8 in 1994. The relative risk for delivery by cesarean section in breech
      presentation compared to the nonbreech population increased from 2.0 (95% CI 1.5
      2.7) in 1967 to 5.9 (95% CI 5.6-6.2) in 1994. It declined by maternal age,
      increased by gestational age and was lowest among mothers with urban residence. A
      negative association was observed between the annual number of births at the
      delivery department and the cesarean section proportion. However, during the
      observation period, the centralization of breech deliveries to the largest
      departments was reduced. CONCLUSIONS: Vaginal delivery in breech presentation was
      particularly observed in large delivery departments and among mothers with urban
      residence. Since experience and practical competence are prerequisites for
      successful vaginal delivery, this centralization seems justified. Further
      centralization of all breech presentation births should be pursued. However,
      preparedness as to vaginal delivery should be established also at the smaller
      units, e.g. by a routine providing periodical centralized training for
      obstetricians working in smaller institutions.

PMID- 9598948
TI  - Improving antenatal care for pregnant adolescents in southern Malawi.
AB  - BACKGROUND: This paper considers why antenatal care (ANC) programs for
      adolescents may need to be improved in areas where a high proportion of first
      pregnancies are to young girls. DESIGN: Descriptive data on the characteristics
      of 615 adolescents (aged 10-19 years) who attended for a first antenatal care
      visit at two rural hospitals in southern Malawi are given. For the 41.5% who came
      for a supervised delivery, details of their pregnancy care and delivery outcome
      are provided. The Chi-square test is used for determining significant differences
      between age and parity groups and logistic regression for an analysis of low
      birthweight. RESULTS: Fifty-two percent of girls were nulliparous, 24.5% were <
      or =16 years and 73.3% were illiterate. Prevalence of anemia, malaria and HIV
      infection was high. Girls who were nulliparous, illiterate, made early antenatal
      care visits or gave a history of stillbirth or abortion were less likely to
      attend for delivery. Few primiparae required an assisted vaginal delivery or
      cesarean section but primiparae had more adverse birth outcomes. Forty percent of
      primiparae <17 years gave birth to low birthweight babies as did 28.3% of
      multiparae. In a logistic regression (all adolescents) low birthweight was
      correlated with literacy (p=0.03) and number of antenatal care visits (p=0.01).
      CONCLUSIONS: Pregnancy morbidity and adverse birth outcomes were common in spite
      of antenatal care attendance. This partly reflects poor management of malaria
      during pregnancy. In areas like Malawi, where childbearing starts early, girls in
      their first pregnancy need good quality care and careful monitoring if problems
      are not to be perpetuated to a second pregnancy. Many girls start pregnancy with
      HIV and schistosomal infections which indicates the need for programs before
      girls become pregnant.

PMID- 9598951
TI  - Attitudes towards pelvic examination in a random sample of Swedish women.
AB  - BACKGROUND: A pelvic examination is the most common procedure in gynecological
      practice. A majority of women have negative experiences of such examinations. The
      aim of the present study was to explore attitudes to and experiences of pelvic
      examinations, as well as possible background factors to such attitudes and
      experiences. METHODS: A postal inquiry was sent to 788 randomly selected Swedish
      women, of fertile age. Sixty-seven per cent answered the questionnaire, which had
      56 items and covered, inter alia, attitudes to and experiences of pelvic
      examinations, as well as possible background factors. RESULTS: The women had
      positive, uniform attitudes to pelvic examinations in general, but negative
      experiences of the specific parts of the procedure. Women's attitudes to and
      experiences of pelvic examinations correlated. The experience of the first pelvic
      examination was more negative than the experience of the last. A negative
      experience in general and the experience of pain during the first pelvic
      examination correlated. The first pelvic examination emerged as a statistically
      powerful background factor for subsequent attitudes to pelvic examinations.
      CONCLUSIONS: Swedish women have positive attitudes to pelvic examination in spite
      of negative previous experiences. A powerful background factor for subsequent
      attitudes to pelvic examination was the experience of the first one. A woman's
      first pelvic examination should therefore be used as an opportunity to condition
      positive emotions and behaviors to the examination situation, as a basis for
      future positive experiences.

PMID- 9598952
TI  - Second-trimester termination of pregnancy by extra-amniotic prostaglandin F2alpha
      or endocervical misoprostol. A comparative study.
AB  - BACKGROUND: To compare the efficacy and side effects of extra-amniotic
      prostaglandin F2alpha with intracervical misoprostol for midtrimester termination
      of pregnancy METHODS: Forty women were randomized to receive either intracervical
      misoprostol or extra-amniotic prostaglandin F2alpha for termination of pregnancy
      for congenital abnormalities or intrauterine fetal death. Induction-abortion
      interval and the incidence of side effects were analyzed for both groups.
      RESULTS: All women in the PGF2alpha group; aborted within 28 hours, 16 (80%) of
      which aborted within 20 hours. Medical termination of pregnancy was complete in
      13 cases (65%). In the misoprostol group; all women aborted within 20 hours, 18
      (90%) of which aborted within 13 hours. Medical termination of pregnancy was
      complete in 17 cases (85%). The induction to abortion intervals for the extra
      amniotic PGF2alpha and intracervical misoprostol were 16+/-5.9 hours, and 10.3+/
      4 hours (mean+/-s.d.) respectively. This was statistically significant (p=0.001).
      The incidence of prostaglandin-associated pyrexia, vomiting and diarrhea were
      significantly increased in the PGF2alpha group (p<0.05). Abdominal pain was
      similar in both groups. There was no post-abortive hemorrhage or infection.
      CONCLUSIONS: Misoprostol is an effective, easy to use, safe and cheap drug for
      termination of second trimester pregnancy. Intracervical administration of
      misoprostol appears to be effective and well-tolerated with less side effects and
      no complications. Larger, randomized comparative studies should be carried out to
      assess its potential advantages.

PMID- 9598954
TI  - Follow up of hysteroscopic surgery for menorrhagia.
AB  - OBJECTIVE: A retrospective study of short and long term results of transcervical
      endomyometrial resection for menorrhagia. MATERIAL AND METHODS: Patient data were
      collected from all 104 premenopausal women who had undergone a transcervical
      endomyometrial resection due to severe menorrhagia in 1990-95. Almost 40% had
      submucous fibromas that were resected together with the endometrium. A
      questionnaire about gynecological symptoms was mailed to all 104 women. Ninety
      seven (93%) women answered the questionnaire. RESULTS: The mean follow-up period
      was 29 months. The following short-term complications were encountered: fluid
      overload in four, one uterine perforation and one major bleeding. The long-term
      complications included: three hematometra and one pregnancy ending in a
      spontaneous abortion. Glandular hyperplasia of the endometrium without atypia was
      found in two cases, and adenomyosis in 31 (29%) cases. Twenty-one women (21%)
      became amenorrhoic after the treatment, whereas forty-nine (51%) had minimal
      menstrual bleeding. Eleven women (11%) suffered from dysmenorrhea. Due to
      dysmenorrhea and/or persistent menorrhagia thirteen (12.5%) underwent a
      hysterectomy, generally within one year after the resection. The histological
      examinations showed adenomyosis in three cases, fibromas in four and fibromas and
      adenomyosis in three cases. CONCLUSIONS: In our hands hysteroscopic transcervical
      endomyometrial resection was a safe and effective treatment for menorrhagia in
      spite of the fact that amenorrhea was not always achieved. However, dysmenorrhea
      appeared in 11% of the women. The reason for this remains to be studied. Correct
      selection criteria is important to get optimal results and reduce the treatment
      failure.

PMID- 9598953
TI  - Tibolone does not have a sustained measurable thermogenic effect in
      postmenopausal women.
AB  - BACKGROUND: Our purpose was to determine if tibolone in commonly used daily
      dosage (2.5 mg/day) would have a measurable thermogenic effect in women, which
      could be attributed to its progestogenic effect. METHODS: We enrolled twelve
      postmenopausal women in this study. Subjects were instructed to take their basal
      body temperatures for fifteen days before and for another fifteen days during
      tibolone usage. Mann-Whitney U test and Wilcoxon matched-pairs signed rank test
      were used in the statistical analysis. RESULTS: Only in one subject did the basal
      body temperatures before and during tibolone usage have a significantly different
      distribution (p=0.048). Mean basal body temperatures before and during tibolone
      usage of the subjects were compared using Wilcoxon matched-pairs signed rank test
      and the p value was found to be 0.158. CONCLUSION: The results of the statistical
      analysis of the basal body temperatures which were taken before and during
      tibolone usage in our group seem to indicate that tibolone does not have a
      sustained measurable thermogenic effect in postmenopausal women.

PMID- 9598955
TI  - Objective methods cannot predict anal incontinence after primary repair of
      extensive anal tears.
AB  - BACKGROUND: An increased awareness of anal incontinence after delivery tears has
      developed during the last years. The aim of this study was to compare complaints
      with the results of physiological methods in women with complete sphincter
      ruptures primarily repaired at delivery. METHODS: Twenty-seven women, 16 with
      total rupture of the external anal sphincter and 11 who also had a ruptured
      internal anal sphincter were studied. Interviews on pelvic floor function,
      investigation with recto-anal manometry, single fiber EMG and anal endosonography
      were performed at 11.9 (2.5) months after delivery. Fifteen women vaginally
      delivered without sphincter rupture served as controls. RESULTS: Pelvic floor
      dysfunction was admitted in 74%, in particular gas incontinence (59%). Maximum
      squeeze pressure was significantly reduced (p<0.01) compared to controls, while
      resting anal pressure was unaffected. Fiber density was increased in 81% of
      patients and 91% had detectable defects on endosonography. Neither the degree of
      rupture nor the presence of complaints significantly correlated to the objective
      methods. CONCLUSIONS: A majority of women with primarily repaired anal sphincter
      ruptures at delivery were incontinent. Sphincter defects and signs of neuropathy
      could not precisely predict symptoms.

PMID- 9598956
TI  - Genital prolapse in women treated successfully and unsuccessfully by the Burch
      colposuspension.
AB  - OBJECTIVE: The aim of the study was to determine the correlation between genital
      prolapse and the outcome of the Burch colposuspension. MATERIAL AND METHODS:
      Fifty women with objectively proven recurrent incontinence after Burch
      colposuspension and 31 women, objectively continent after the colposuspension,
      were clinically examined with emphasis on genital prolapse. The preoperative
      vaginal profile of the women was estimated from the patient records. RESULTS: The
      preoperative vaginal profile demonstrated no significant differences in
      occurrence of prolapse components between the women who were continent after the
      colposuspension and those women who had recurrent incontinence. At the follow-up,
      rectocele and cystocele occurred with significantly higher frequencies among the
      women with recurrent urinary incontinence than among the women who were continent
      after the Burch colposuspension (80% and 46% vs. 42% and 10%; p<0.01). Enterocele
      and uterine/vaginal vault descent occurred in equal frequencies in the two
      groups. Independent of the outcome of the colposuspension, the women with
      rectocele were significantly younger than the women without rectocele (55 years
      vs. 63.5 years; p<0.01). CONCLUSIONS: The results imply an association between
      the occurrence of rectocele and cystocele and the outcome of the colposuspension.
      Different etiologies seem to exist for rectocele/cystocele, compared to
      enterocele or uterine/vaginal vault descent formation in women with stress
      urinary incontinence, operated upon with the Burch colposuspension.

PMID- 9598957
TI  - Management and outcome of borderline ovarian tumors incidentally discovered at or
      after laparoscopy.
AB  - BACKGROUND: To evaluate in a series of patients with borderline ovarian tumors
      the clinical findings and the outcome after laparoscopic management. METHODS:
      Retrospective study of 25 patients with borderline ovarian tumors first treated
      by laparoscopic approach. RESULTS: Thirteen patients had mucinous tumors and 12
      had serous tumors. Twenty-one patients had ultrasound examination which detected
      24 ovarian cysts including multilocular cysts in 50% of cases and unilocular
      sonolucent cysts in 25% of cases. The serum CA 125 and CA 199 levels were
      elevated in 30.7% and 23% respectively. Among the 25 patients first treated by
      laparoscopic approach, 24 had stage I disease: six of them had cystectomy, seven
      unilateral salpingo-oophorectomy, two bilateral salpingo-oophorectomy and two
      laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Seven patients
      had laparoconversion for presumption of ovarian cancer (5) and failure of
      laparoscopic procedure (2). One patient with stage III disease had laparoscopic
      biopsies and subsequent laparotomy. Among the 25 patients, 15 had conservative
      treatment and 10 had radical treatment. Three recurrences occurred after
      cystectomy. The mean follow-up was 41 months. Twenty-three patients were alive
      without evidence of disease, one died of intercurrent disease and one patient was
      lost to follow-up. CONCLUSION: Our data suggest that the laparoscopic approach to
      borderline ovarian tumors is possible in early stage disease but associated with
      a high risk of recurrence after cystectomy.

PMID- 9598958
TI  - Clinical implications of BRCA1 genetic testing.

PMID- 9598959
TI  - Pregnancy after intracytoplasmatic sperm injection (ICSI) of cryopreserved human
      oocytes.

PMID- 9598960
TI  - Heterotopic pregnancy after in vitro fertilization and embryo transfer.

PMID- 9598961
TI  - The first-trimester ultrasonographic diagnosis of dicephalus conjoined twins.

PMID- 9598962
TI  - Prenatal detection of human cytomegalovirus DNA in fetal ascites by the
      polymerase chain reaction.

PMID- 9598963
TI  - Premature ovarian failure associated with a Robertsonian translocation.

PMID- 9598964
TI  - Gastric cancer as an essential differential diagnosis of minor epigastric
      discomfort during pregnancy.

PMID- 9598965
TI  - Prolapse of Filshie clips following vaginal hysterectomy.

PMID- 9598966
TI  - Zero of nine may be 30%, and a 10% risk isn't zero.

PMID- 9598967
TI  - Differential genome analysis applied to the species-specific features of
      Helicobacter pylori.
AB  - We introduce a simple and rapid strategy to identify genes that are responsible
      for species-specific phenotypes. The genome of a species that has a specific
      phenotype is compared with at least one, closely related, species that lacks this
      phenotype. Homologous genes that are shared among the species compared are
      identified and discarded from the list of candidates for species-specific genes.
      The process is automated and rapidly yields a small subset of the genome that
      likely contains genes responsible for the species-specific features. Functions
      are assigned to the genes, and dubious annotations are filtered out. Information
      is extracted not only from the presence of genes, but also from their absence
      with respect to known phenotypes. We have applied the technique to identify a set
      of species-specific genes in Helicobacter pylori by comparing it with its closest
      relatives for which complete genome sequences are available, Haemophilus
      influenzae and Escherichia coli. Of the genes of this set for which functional
      features can be obtained, a large fraction (63%, 123 proteins) is (potentially)
      involved in H. pylori's interaction with its host. We hypothesize that a family
      of outer membrane proteins is critical for the ability of H. pylori to colonize
      host cells in highly acidic environments.

PMID- 9598968
TI  - Updated catalogue of homologues to human disease-related proteins in the yeast
      genome.
AB  - The recent availability of the full Saccharomyces cerevisiae genome offers a
      perfect opportunity for revising the number of homologues to human disease
      related proteins. We carried out automatic analysis of the complete S. cerevisiae
      genome and of the set of human disease-related proteins as identified in the
      SwissProt sequence data base. We identified 285 yeast proteins similar to 155
      human disease-related proteins, including 239 possible cases of human-yeast
      direct functional equivalence (orthology). Of these, 40 cases are suggested as
      new, previously undiscovered relationships. Four of them are particularly
      interesting, since the yeast sequence is the most phylogenetically distant member
      of the protein family, including proteins related to diseases such as
      phenylketonuria, lupus erythematosus, Norum and fish eye disease and Wiskott
      Aldrich syndrome.

PMID- 9598969
TI  - The mode of action of peptidyl prolyl cis/trans isomerases in vivo: binding vs.
      catalysis.
AB  - Polypeptides often display proline-mediated conformational substates that are
      prone to isomer-specific recognition and function. Both possibilities can be of
      biological significance. Distinct families of peptidyl prolyl cis/trans
      isomerases (PPIases) evolved proved to be highly specific for proline moieties
      arranged in a special context of subsites. Structural and chemical features of
      molecules specifically bound to the active site of PPIases served to improve
      catalysis of prolyl isomerization rather than ground state binding. For example,
      results inferred from receptor Ser/Thr or Tyr phosphorylation in the presence of
      site-directed FKBP12 mutant proteins provided evidence for the crucial role of
      the enzymatic activity in downregulating function of FKBP12.

PMID- 9598970
TI  - IncI1 plasmid R64 encodes the ArsR protein that alleviates type I restriction.
AB  - The host-controlled EcoK restriction of unmodified phage lambda was five-fold
      alleviated in the wild-type Escherichia coli strain K12 carrying the R64 plasmid
      of the incompatibility group I1. The relevant gene was mapped between the origin
      of vegetative replication (rep, oriV) and the tet(r) gene about 60 kbp downstream
      from the origin of transfer, oriT. We cloned this gene inside the 613 bp long
      EcoRI-PstI fragment and sequenced it. Only one 351 bp long open reading frame
      (ORF) starting at 124 bp from the beginning of the insert was found in the
      sequence. Computer search in the current databases revealed that the putative
      protein is identical to the ArsR protein specified by the IncFI plasmid R773.
      ArsR is a repressor of the arsenical resistance (ars) operon, arsRDABC. There are
      no arsABC genes in the R64 plasmid since plasmid R64- (or pSR8)-mediated
      resistance of E. coli K12 cells to the arsenicals arsenate and arsenite was not
      detected. The gene arsR and the antirestriction genes ard (ardA and ardB) are non
      homologous. However, comparison of the deduced amino acid sequence of ArsR with
      the ArdA and ArdB sequences revealed only one small region of similarity, a 9
      amino acid motif found in different antirestriction proteins that is hypothesized
      to be an interaction site for antirestriction proteins with restriction
      endonucleases.

PMID- 9598971
TI  - Scavenging of peroxynitrite by a phenolic/peroxidase system prevents oxidative
      damage to DNA.
AB  - We examined the ability of horseradish peroxidase (HRP), an analog of human
      myeloperoxidase, to protect DNA against oxidative damage caused by peroxynitrite
      in the presence of chlorogenic acid (CGA), a naturally occurring polyphenol.
      Chlorogenic acid inhibits the formation of single strand breaks in supercoiled
      pBR322 DNA by acting as a scavenger of peroxynitrite. Horseradish peroxidase
      markedly enhances the extent of DNA protection by catalyzing the decomposition of
      peroxynitrite in the presence of CGA. Horseradish peroxidase alone does not
      inhibit peroxynitrite-induced DNA strand breaks, indicating that CGA is required
      as an electron donor to regenerate the active enzyme. The apparent second order
      rate constant for the HRP-mediated oxidation of CGA in the presence of
      peroxynitrite at pH 6.9 is 3.4 x 10(7) M(-1) s(-1). This high rate suggests that
      CGA and other dietary polyphenols might efficiently scavenge peroxynitrite in
      peroxidase-containing systems in vivo.

PMID- 9598972
TI  - Zeatin is indispensable for the G2-M transition in tobacco BY-2 cells.
AB  - The importance of N6-isoprenoid cytokinins in the G2-M transition of Nicotiana
      tabacum BY-2 cells was investigated. Both cytokinin biosynthesis and entry in
      mitosis were partially blocked by application at early or late G2 of lovastatin
      (10 microM), an inhibitor of mevalonic acid synthesis. LC-MS/MS quantification of
      endogenous cytokinins proved that lovastatin affects cytokinin biosynthesis by
      inhibiting HMG-CoA reductase. Out of eight different aminopurines and a synthetic
      auxin tested for their ability to override lovastatin inhibition of mitosis, only
      zeatin was active. Our data point to a key role for a well-defined cytokinin
      (here, zeatin) in the G2-M transition of tobacco BY-2 cells.

PMID- 9598973
TI  - Synthesis and characterization of a specific peptide nucleic acid that inhibits
      expression of inducible NO synthase.
AB  - Inducible nitric oxide synthase (iNOS) is modulated at the transcriptional level.
      Overexpression of this protein may result in high levels of nitric oxide leading
      to tissue damage and immunosuppression. In order to reduce the pathological
      effects of NO overproduction many efforts have been devoted to the identification
      of specific inhibitors of iNOS. The discovery of peptide nucleic acids (PNA), a
      novel class of molecules able to selectively interact with nucleic acids,
      prompted us to attempt a new way for the regulation of NO production. Here we
      describe the synthesis, characterization and in vitro effects of a PNA molecule
      bearing a homopyrimidine sequence complementary to the 5' coding region of murine
      iNOS mRNA. This PNA shows specific interactions with iNOS mRNA in RNase
      protection assays and is able to block the synthesis of iNOS protein selectively
      in a rabbit reticulocyte lysate system. These results strengthen the view of a
      possible pharmacological application of PNA as a compound able to interfere with
      a specific enzymatic activity even at low concentrations.

PMID- 9598974
TI  - Trapping of conformations of the Escherichia coli F1 ATPase by disulfide bond
      formation. A state of the enzyme with all three catalytic sites of equal and low
      affinity for nucleotides.
AB  - A mutant of Escherichia coli F1F0-ATPase,
      alphaS411C/betaY331W/betaE381C/gammaC87S, has been generated. CuCl2 treatment of
      this mutant led to cross-linking between alpha and beta subunits in yields of up
      to 90%. This cross-linking across non-catalytic site interfaces inhibited ATP
      hydrolysis activity. In the absence of cross-linking, MgATP bound in catalytic
      sites of the mutant with three different affinities of 0.1 microM, 6 microM and
      60 microM, respectively, values that are comparable to wild-type. For MgADP,
      there was one tight site (0.34 microM) and two sites of lower affinity (each 27
      microM), again comparable to wild-type enzyme. After cross-linking all three
      catalytic sites bound MgATP or MgADP with the same relatively low affinity
      (approximately 60 microM). Thus cross-linking fixed all three catalytic sites in
      the same conformation. Trypsin cleavage experiments showed that cross-linking
      fixed the epsilon subunit in the ATP+EDTA conformation.

PMID- 9598975
TI  - Serpin-like properties of alpha1-antitrypsin Portland towards furin convertase.
AB  - Recent studies have demonstrated that a serpin variant, alpha1-antitrypsin
      Portland (AT-PDX), can inhibit the mammalian convertase furin. Here, we examine
      the mechanism by which this inhibition takes place. We find that furin, which
      does not belong to the trypsin-like serine protease family, the usual targets of
      serpins, forms an SDS-heat denaturation-resistant complex with AT-PDX both in
      vitro and in vivo. AT-PDX inhibited furin with an association rate constant
      (k(ass)) of 1.5 x 10(6) M(-1) s(-1) which is similar to k(ass) values reported
      for serpins with trypsin-like enzymes. These results illustrate that AT can be
      modified to act essentially as a suicide inhibitor of furin, an enzyme of the
      subtilase superfamily of serine proteases.

PMID- 9598976
TI  - Mouse sperm patch-clamp recordings reveal single Cl- channels sensitive to
      niflumic acid, a blocker of the sperm acrosome reaction.
AB  - Ion channels lie at the heart of gamete signaling. Understanding their regulation
      will improve our knowledge of sperm physiology, and may lead to novel
      contraceptive strategies. Sperm are tiny (approximately 3 microm diameter) and,
      until now, direct evidence of ion channel activity in these cells was lacking.
      Using patch-clamp recording we document here, for the first time, the presence of
      cationic and anionic channels in mouse sperm. Anion selective channels were
      blocked by niflumic acid (NA) (IC50 = 11 microM). The blocker was effective also
      in inhibiting the acrosome reaction induced by the zona pellucida, GABA or
      progesterone. These observations suggest that Cl- channels participate in the
      sperm acrosome reaction in mammals.

PMID- 9598977
TI  - Expression, purification and preliminary crystal analysis of the human low Mr
      phosphotyrosine protein phosphatase isoform 1.
AB  - The genes of the human low Mr phosphotyrosine protein phosphatase (PTPase)
      isoforms 1 (IF1) and 2 (IF2) were isolated by screening a human placenta cDNA
      library, cloned in pGEX and expressed in E. coli as fusion proteins with
      glutathione S-transferase. The recombinant proteins were purified by a rapid one
      step procedure allowing each enzyme to purify with high final yield and specific
      activity. This result is important for IF1, whose purification from natural
      sources is difficult, due to precipitation propensity, thus hindering structural
      studies. The enzymes obtained showed kinetic parameters very similar to those
      previously determined for the enzymes purified by classical procedures from both
      human erythrocytes and rat liver. These recombinant enzymes can therefore be used
      in place of those purified from natural sources for every purpose. IF1 and IF2
      crystals were also grown. IF1 crystals were X-ray-grade, diffracted to better
      than 2.4 A and were suitable for high resolution X-ray structure determination.

PMID- 9598978
TI  - Repulsive interparticle interactions in a denatured protein solution revealed by
      small angle neutron scattering.
AB  - In order to investigate the effect of concentration in biological processes such
      as protein folding, small angle neutron scattering measurements were used to
      determine the second virial coefficient of solutions of both native and strongly
      denatured phosphoglycerate kinase and the radius of gyration of the protein at
      zero concentration. The value of the second virial coefficient is a good probe of
      the non-ideality of a solution. The present results show that the unfolding of
      the protein leads to a drastic change in the repulsive intermolecular
      interactions. We conclude that these interactions are due mainly to the behaviour
      of the denatured polypeptide chain as an excluded volume polymer.

PMID- 9598979
TI  - Maize polyamine oxidase: primary structure from protein and cDNA sequencing.
AB  - The first complete amino acid sequence of a flavin-containing polyamine oxidase
      was solved by a combined approach of nucleotide and peptide sequence analysis. A
      cDNA of 1737 bp, isolated from maize seedlings by reverse transcription
      polymerase chain reaction and rapid amplification of cDNA ends strategies, was
      cloned and its sequence determined. This cDNA contains information for a
      polypeptide chain of 500 amino acids. Its amino-terminal sequence shows the
      typical features of secretion signal peptides. The primary structure of the
      mature protein was independently confirmed by extensive amino acid sequencing.
      Structural relationships with flavin-containing monoamine oxidases are also
      discussed.

PMID- 9598980
TI  - Identification and location on syndecan-1 core protein of the epitopes of B-B2
      and B-B4 monoclonal antibodies.
AB  - Using a phage display peptide library, we characterized the epitope of two
      monoclonal antibodies reacting with syndecan-1: B-B2 and B-B4. The identified
      epitopes QDIT, for B-B2, and LPEV, for B-B4, were found to align with residues 36
      39 and 90-93 of the mature protein, respectively. In contrast to B-B4, the B-B2
      epitope is close to a potential glycosaminoglycan attachment site. Since syndecan
      1 is heavily glycosylated and post-translational modifications are cell type
      specific, these results might explain the differences observed in the reactivity
      pattern of B-B2 and B-B4 and suggest that these monoclonal antibodies are useful
      probes to study cell surface exposed syndecan-1.

PMID- 9598981
TI  - Structural analysis and proteolytic processing of recombinant G domain of mouse
      laminin alpha2 chain.
AB  - Four individual LG modules from the C-terminus of the laminin alpha2 chain (LG1,
      LG2, LG4 and LG5) and combinations of these modules were prepared as recombinant
      products from transfected mammalian cells. This demonstrated that LG modules
      represent autonomously folding protein domains. Successful production depended on
      proper alignment of module borders and required a sequence correction at the C
      terminus which added an extra cysteine. The LG modules were glycosylated and
      shown by electron microscopy to have a globular shape, indicating proper folding.
      Evidence is provided for the splicing of a 12 bp exon in LG2, although this did
      not impair folding. Proteolytic cleavage at the C-terminus of a basic sequence
      was observed close to the N-terminus of LG3. A similar processing also occurs in
      tissue-derived laminin-2 and -4 which contain the alpha2 chain.

PMID- 9598983
TI  - Oct-1 promoter region contains octamer sites and TAAT motifs recognized by Oct
      proteins.
AB  - The 5'-upstream region (1.3 kb) of the gene encoding the POU domain transcription
      factor Oct-1 was cloned and sequenced. CAT reporter gene analysis of this region
      has detected a functionally active promoter. This region contains 24 TAAT-core
      sites, arranged in five clusters (four to six sites in one cluster); two octamer
      sites (ATGCAAAT) are located in the first and second clusters; in the second one
      the CCAAT-box adjacent to the octamer overlaps with the TAAT-core site. As shown
      by gel retardation assay, Oct-1, Oct-2, and some unknown proteins from myeloma
      cell line NS/0 interact with the TAAT-core sites of these clusters. The results
      suggest autoregulation of Oct-1 gene expression that may also be controlled by
      other POU proteins, homeodomain proteins and CCAAT trans-action factors.

PMID- 9598982
TI  - A high diffusion coefficient for coenzyme Q10 might be related to a folded
      structure.
AB  - We measured the lateral diffusion of different coenzyme Q homologues and
      analogues in model lipid vesicles using the fluorescence collisional quenching
      technique with pyrene derivatives and found diffusion coefficients in the range
      of 10(-6) cm2/s. Theoretical diffusion coefficients for these highly hydrophobic
      components were calculated according to the free volume theory. An important
      parameter in the free volume theory is the relative dimension between diffusant
      and solvent: a molecular dynamics computer simulation of the coenzymes yielded
      their most probable geometries and volumes and revealed surprisingly similar
      sizes of the short and long homologues, due to a folded structure of the
      isoprenoid chain in the latter, with a length for coenzyme Q10 of 21 A. Using
      this information we were able to calculate diffusion coefficients in the range of
      10(-6) cm2/s, in good agreement with those found experimentally.

PMID- 9598984
TI  - A transcription frame-based analysis of the genomic DNA sequence of a hyper
      thermophilic archaeon for the identification of genes, pseudo-genes and operon
      structures.
AB  - An algorithm for identifying transcription units, independently regulated genes
      and operons, and pseudo-genes that are not expected to be expressed, has been
      developed by combining a system for predicting transcription and translation
      signals, and a system for scoring the triplet periodicity in ORF candidates. By
      using the algorithm, the 1.09 Mb sequence that covers approximately 60% of the
      genome of Pyrococcus sp. OT3 has been analyzed. The identified ORFs show the
      expected biological and physical characteristics, while the rejected ORF
      candidates do not. Frequent use of operon structures for transcription, and gene
      duplication followed by mutation or termination of the duplicated genes, are
      discussed.

PMID- 9598985
TI  - The p38-MAPK inhibitor, SB203580, inhibits cardiac stress-activated protein
      kinases/c-Jun N-terminal kinases (SAPKs/JNKs).
AB  - SB203580 is a recognised inhibitor of p38-MAPKs. Here, we investigated the
      effects of SB203580 on cardiac SAPKs/JNKs. The IC50 for inhibition of p38-MAPK
      stimulation of MAPKAPK2 was approximately 0.07 microM, whereas that for total
      SAPK/JNK activity was 3-10 microM. SB203580 did not inhibit immunoprecipitated
      JNK1 isoforms. Three peaks of SAPK/JNK activity were separated by anion exchange
      chromatography, eluting in the isocratic wash (44 kDa), and at 0.08 M (46 and 52
      kDa) and 0.15 M NaCl (54 kDa). SB203580 (10 microM) completely inhibited the 0.15
      M NaCl activity and partially inhibited the 0.08 M NaCl activity. Since JNK1
      antibodies immunoprecipitate the 46 kDa activity, this indicates that SB203580
      selectively inhibits 52 and 54 kDa SAPKs/JNKs.

PMID- 9598986
TI  - Reconstituted adenine nucleotide translocase forms a channel for small molecules
      comparable to the mitochondrial permeability transition pore.
AB  - Highly purified adenylate translocase (ANT) from rat heart mitochondria was
      functionally reconstituted as ATP/ADP exchange carrier in asolectin/cardiolipin
      vesicles. The ANT preparations used were free of porin, cyclophilin D, and Bax as
      analysed immunologically and by activity measurements. After pre-loading the ANT
      containing proteoliposomes with ATP, malate or AMP, a gradual release of the
      trapped compounds by increasing the external Ca2+ concentrations could be
      demonstrated. N-Methyl-Val-4-cyclosporin did not inhibit the Ca2+ dependent
      release of internal substances from ANT liposomes. This inhibitor was found to be
      specific for the mitochondrial permeability transition pore (MTP) in intact
      mitochondria or reconstituted MTP-like protein complexes (e.g. hexokinase, porin,
      ANT complex). However, ADP in concentrations > 20 microM inhibited the liberation
      of internal compounds, while in contrast, atractyloside (30 microM) and HgCl2 (5
      microM) both induced permeability of the ANT-containing liposomes resulting in a
      release of trapped substances. These results strongly suggest that ANT itself is
      capable to adopt a pore-like structure under conditions known to induce the
      permeability transition in mitochondria.

PMID- 9598987
TI  - Natural ceramide is unable to escape the lysosome, in contrast to a fluorescent
      analogue.
AB  - Since the generation upon cell stimulation of the second messenger ceramide has
      been reported to occur in an endosomal/lysosomal compartment, we investigated
      whether ceramide formed in the lysosomes can escape this compartment. The
      metabolic fate of radiolabelled ceramide produced by intralysosomal hydrolysis of
      LDL-associated [ceramide-3H]sphingomyelin or [stearoyl-1-(14)C]sulfatide was
      examined in fibroblasts from control individuals and a patient with inborn
      lysosomal ceramidase deficiency (Farber disease). The behavior of this
      radioactive ceramide was compared to that of a fluorescent (lissamine-rhodaminyl)
      ceramide analogue deriving from sulfatide degradation. While in Farber cells the
      natural, radiolabelled ceramide remained completely undegraded and accumulated in
      the lysosomes, the fluorescent derivative was rapidly converted to sphingomyelin.
      These findings strongly suggest that, in contrast to fluorescent derivatives,
      endogenous long-chain ceramide is unable to exit from lysosomes, therefore making
      the lysosomal ceramide unlikely to be a biomodulatory molecule.

PMID- 9598988
TI  - Study on the interactions between protein disulfide isomerase and target
      proteins, using immobilization on solid support.
AB  - Interaction between protein disulfide isomerase, possessing not only isomerase
      but also chaperone-like activity, and olygomeric enzyme, GAPDH, has been studied
      using technique of immobilization on insoluble support. PDI dimers bound to CNBr
      activated Sepharose were shown to possess high TPOR activity as well as the
      ability to reactivate lysozyme. Immobilized PDI was not found to interact neither
      with soluble tetrameric GAPDH, nor with soluble denatured GAPDH. However, soluble
      PDI binds effectively to immobilized GAPDH monomers; Kd was found to be 3.7 x 10(
      6) M, stoichiometry 0.824 mole PDI monomers per mole GAPDH monomers. Immobilized
      GAPDH tetramers do not interact with PDI. These observations are also confirmed
      by the data on electrophoresis of proteins bound to immobilized GAPDH monomers
      and tetramers. The ability of PDI to interact with denatured protein form, but
      not with the native one, is considered to be evidence of chaperone-like activity
      of the enzyme.

PMID- 9598989
TI  - Disruption of the outer mitochondrial membrane as a result of large amplitude
      swelling: the impact of irreversible permeability transition.
AB  - Upon induction of permeability transition with different agents (Ca2+, tert-butyl
      hydroperoxide, atractyloside), mouse hepatocyte mitochondria manifest a
      disruption of outer membrane integrity leading to the release of cytochrome c and
      apoptosis-inducing factor (AIF), two proteins which are involved in programmed
      cell death (apoptosis). Chelation of Ca2+ shortly (within 2 min) after its
      addition to isolated mitochondria reestablished the mitochondrial transmembrane
      potential (deltapsi(m)), prevented induction of large amplitude swelling and
      release of both cytochrome c and AIF. In contrast, late Ca2+ chelation (10 min
      after addition of Ca2+) failed to affect these parameters. Cytochrome c appears
      to be released through a mechanically damaged outer mitochondrial membrane rather
      than via a specific release mechanism. These findings clarify the mechanisms
      through which irreversible permeability transition occurs with subsequent large
      amplitude swelling culminating in the release of intermembrane proteins from
      mitochondria. Moreover, they confirm the hypothesis formulated by Skulachev [FEBS
      Lett. 397 (1996) 7-10 and Q. Rev. Biophys. 29 (1996) 169-2021 linking
      permeability transition to activation of the apoptogenic catabolic enzymes.

PMID- 9598990
TI  - Heterologous coexpression of the blue light receptor psRII and its transducer
      pHtrII from Natronobacterium pharaonis in the Halobacterium salinarium strain
      Pho81/w restores negative phototaxis.
AB  - The photophobic receptor (psRII) and its transducer pHtrII from Natronobacterium
      pharaonis were heterologously coexpressed in the phototaxis-deficient
      Halobacterium salinarium strain Pho81/w which lacks all four bacterial
      rhodopsins, i.e. the two ion pumps bacteriorhodopsin and halorhodopsin as well as
      the two sensory pigments SRI and SRII. This genetically transformed Pho81/w
      strain showed a photophobic response upon illumination with blue light. The
      action spectrum of the psRII/pHtrII mediated phototactic behavior was determined
      in the range of 420-600 nm. The shape of the action spectrum was similar to the
      absorption spectrum of psRII, clearly indicating that the psRII-specific
      photophobic response in Pho81/w was restored. These results suggest that the
      pharaonis photoreceptor-transducer complex (psRII/pHtrII) is functionally
      competent to substitute the corresponding salinarium receptor system. Although
      the two archaea are phylogenetically quite distant from each other the two signal
      transduction chains are homologous systems which can replace each other.

PMID- 9598991
TI  - The skin-type antifreeze protein gene intron of the winter flounder is a
      ubiquitous enhancer lacking a functional C/EBPalpha binding motif.
AB  - The winter flounder antifreeze protein (AFP) intron contains a liver-specific
      enhancer (Element B) which was shown earlier to bind CCAAT/enhancer binding
      protein (C/EBP)alpha. In contrast, as demonstrated in the present studies, the
      intron of the skin-type AFP gene acted as a ubiquitous enhancer and contained a
      TA insertion at similar region to Element B (Element S) which destroyed its
      interaction with C/EBPalpha. Furthermore, a TA insertion of Element B by site
      directed mutagenesis decreased its liver enhancer activity. The presence or
      absence of C/EBPalpha binding motifs in Element B and Element S, respectively,
      may provide a mechanism for their differential expression.

PMID- 9598992
TI  - Two distinct states of the thylakoid bf complex.
AB  - Under normal physiological conditions the state of the cyt bf complex is
      characterized by rapid reoxidation kinetics of cyt b-563 following flash
      illumination. It is known that these kinetics are dramatically slowed down under
      oxidizing conditions. Here we show that this slow-down of cyt b-563 oxidation is
      the consequence of a relatively slow (half-time of several minutes)
      transformation of the cyt bf complex into a distinctly different state (termed
      state-s). Reversal to the normal state requires strong reductive treatment or
      light-induced electron transport. The results are in line with a recent model of
      functional cyt bf dimers [Cramer et al., Annu. Rev. Plant Physiol. Plant Mol.
      Biol. 47 (1996), 477-5081, if it is assumed that state-s reflects the monomeric
      state of the bf complex.

PMID- 9598993
TI  - Kunitz-type proteinase inhibitors from intact and Phytophthora-infected potato
      tubers.
AB  - Three protein proteolytic enzyme inhibitors with molecular masses 21, 22, and 23
      kDa have been isolated from intact potato tubers (Solanum tuberosum L. cv.
      Istrinskii). The 21 and 22 kDa proteins denoted as PSPI-21 and PSPI-22,
      respectively, are serine proteinase inhibitors with different specificity. The 23
      kDa protein denoted as PCPI-23 is an inhibitor of plant cysteine proteinases. The
      PSPI-21 molecule consists of two disulfide-linked polypeptide chains with
      molecular masses of 16.5 kDa and 4.5 kDa. The PSPI-22 and PCPI-23 have one
      polypeptide chain. Their amino-termini numbered 21-25 amino acid residues have
      significant homology to other plant inhibitors which are members of the soybean
      Kunitz inhibitor family. It is found that at least PSPI-21 and PSPI-22 can
      predominantly accumulate in potato tubers infected with Phytophthora infestans
      zoospores.

PMID- 9598994
TI  - Aminoacylation of tRNA gene transcripts is strongly affected by 3'-extended and
      dimeric substrate RNAs.
AB  - Kinetic parameters of aminoacylation by E. coli phenylalanyl-tRNA synthetase vary
      for phage T5 tRNA(Phe) gene transcript from 0.950 to 2.545 microM for Km and from
      550 to 400 min(-1) for kcat. To reveal the source of this variability for various
      RNA preparations, homogeneity of the transcripts has been examined. Presence of
      3' extensions and dimer formation in transcript preparations reduced the
      catalytic efficiency kcat/Km several-fold. We have shown that the proportion of
      dimers and 3'-extended transcripts in tRNA preparations is sensitive to single
      base substitutions in tRNA. While wild-type phage T5 tRNA(Phe) gene transcript
      contains about half of dimeric molecules, for some mutants this value increases
      up to 90% or drops to 0%. Phage T5 tRNA(Phe) gene with anticodon stem nucleotide
      substitutions used as a template in run-off transcription produces 5 times less
      3'-extended molecules than the wild-type gene. In view of all these results
      kinetic parameters of aminoacylation reaction for many wild-type and mutant tRNA
      gene transcripts should be reevaluated.

PMID- 9598995
TI  - Rapid and discrete isolation of oxygen-evolving His-tagged photosystem II core
      complex from Chlamydomonas reinhardtii by Ni2+ affinity column chromatography.
AB  - We have developed a simple and rapid procedure to isolate an oxygen-evolving
      photosystem II (PS II) core complex from Chlamydomonas reinhardtii. A His-tag
      made of six consecutive histidine residues was genetically attached at the
      carboxy terminus of D2 protein to create a metal binding site on the PS II
      supramolecular complex. The recombinant cells producing the His-tagged variant of
      D2 protein grew photoautotrophically as well as the wild-type cells.
      Characterization of the oxygen evolution and the thermoluminescence properties
      revealed that the His-tagging did not affect the functional integrity of the PS
      II reaction center. A PS II core complex was isolated from the detergent
      solubilized thylakoids of the recombinant cells in 4 h by a single one-step Ni2+
      affinity column chromatography. This preparation consists of D1, D2, CP43, CP47,
      33 kDa, and a few low molecular weight proteins, and retains a high rate of
      oxygen-evolving activity (= 1000 micromol/mg Chl/h).

PMID- 9598996
TI  - Diphospho-myo-inositol phosphates in Dictyostelium and Polysphondylium:
      identification of a new bisdiphospho-myo-inositol tetrakisphosphate.
AB  - The two major diphospho inositol phosphates from the axenic strain Dictyostelium
      discoideum AX2 were previously investigated and identified as 6-PP-InsP5 and 5,6
      bis-PP-InsP4. In order to examine whether these findings are representative of
      Dictyostelids in general, five non-axenic wild-type species of Dictyostelium and
      two of Polysphondylium were studied. It was found that all of the Dictyostelium
      species exhibit similar patterns of diphospho inositol phosphates. By contrast,
      both of the Polysphondylium species contain 5-PP-InsP5 as the predominant isomer.
      Besides 5,6-bis-PP-InsP4, a new bis-PP-InsP4 was detected in Polysphondylium.
      This compound is either 1,5-bis-PP-InsP4 or its corresponding enantiomer 3,5-bis
      PP-InsP5. The structures were elucidated by two-dimensional 1H-1H and 1H-31P NMR
      analysis. Additionally, they were confirmed using a specific 6-PP-InsP(5)-5
      kinase from D. discoideum AX2 as an enantio-specific tool and enantiomerically
      pure reference standards.

PMID- 9598997
TI  - Activation of caspases triggered by cytochrome c in vitro.
AB  - Previous studies have shown that Apaf-1 and caspase-9 in the presence of
      cytochrome c and dATP can form an initiating complex for an apoptotic protease
      cascade. We have developed a cytochrome c-dependent in vitro system in which
      caspases downstream of this initiation complex are activated. The activation of
      caspase-9 from zymogen form to active dimeric protease requires intrinsic
      enzymatic activity. In contrast, caspase-3 and caspase-7 zymogens are
      proteolytically processed by active caspase-9. Activation of the above caspases
      is blocked by a dominant negative form of caspase-9. The in vitro system displays
      surprising specificity in that other caspases, including 1, 2, 4, 8, 10, and 13,
      are not activated.

PMID- 9598998
TI  - Protection against apoptosis by monoamine oxidase A inhibitors.
AB  - Several lines of evidence have been accumulating indicating that an important
      role may be played by mitochondrial homeostasis in the initiation phase, the
      first stage of apoptosis. This work describes the results obtained by using
      different inhibitors of monoamine oxidases (MAO), i.e. pargyline, clorgyline and
      deprenyl, on mitochondrial integrity and apoptosis. Both pargyline and clorgyline
      are capable of protecting cells from apoptosis induced by serum starvation while
      deprenyl is ineffective. These data represent the first demonstration that MAO-A
      inhibitors may protect cells from apoptosis through a mechanism involving the
      maintenance of mitochondrial homeostasis.

PMID- 9598999
TI  - Na+-ATPase from the plasma membrane of the marine alga Tetraselmis (Platymonas)
      viridis forms a phosphorylated intermediate.
AB  - Plasma membranes isolated from the marine unicellular alga Tetraselmis
      (Platymonas) viridis were phosphorylated by [gamma-32P]ATP, and membrane proteins
      were then analyzed by PAGE in SDS, under acidic conditions. Three radioactive
      components with apparent molecular masses of 100 kDa, 76 kDa, and 26 kDa were
      detected. The phosphorylation of one of them, the 100 kDa polypeptide, was
      specifically stimulated by Na+. Vanadate almost completely inhibited the Na+
      mediated phosphorylation of the peptide. The phosphate bound to this peptide
      underwent rapid turnover and was discharged by hydroxylamine. The 100 kDa
      phosphopeptide was sensitive to ADP. The conclusion is drawn that the 100 kDa
      phosphopeptide is a phosphorylated intermediate of the Na+-transporting ATPase in
      the T. viridis plasma membrane.

PMID- 9599000
TI  - Peptide-specific antibodies localize the major lipid binding sites of talin
      dimers to oppositely arranged N-terminal 47 kDa subdomains.
AB  - Using ultrastructural analysis and labeling with polyclonal antibodies that
      recognize peptide sequences specific for phospholipid binding, we mapped the
      functional domain structure of intact platelet talin and its proteolytic
      fragments. The talin dimer, which is crucial for actin and lipid binding, is
      built of a backbone containing the 200 kDa rod portions, at both ends of which a
      47 kDa globular domain is attached. Peptide-specific polyclonal antibodies were
      raised against three potential lipid binding sequences residing within the N
      terminal 47 kDa domain (i.e. S19, amino acids 21-39; H18, amino acids 287-304;
      and H17, amino acids 385-406). Antibodies H17 and H18 localize these lipid
      binding sequences within the N-terminal 47 kDa globular talin subdomains opposed
      at the outer 200 kDa rod domains within talin dimers. Hence, we conclude that in
      its dimeric form, which is used in actin and lipid binding, talin is a dumbbell
      shaped molecule built of two antiparallel subunits.

PMID- 9599001
TI  - The GXGXG motif in the pI(Cln) protein is not important for the nucleotide
      sensitivity of the pI(Cln)-induced Cl- current in Xenopus oocytes.
AB  - It has been proposed that the pI(Cln) protein forms a nucleotide-sensitive plasma
      membrane anion channel with a GXGXG motif being an essential component of the
      extracellular nucleotide-binding site. To evaluate this hypothesis, we have
      performed voltage-clamp experiments on Xenopus laevis oocytes injected with RNA
      encoding a rat mutant pI(Cln) in which the three glycines of the putative
      nucleotide-binding site have been changed into alanines (G54A; G56A; G58A). The
      injected oocytes displayed outwardly rectifying anion currents, which were
      voltage-dependently blocked by extracellular cAMP, but which were not affected by
      removal of extracellular Ca2+. Furthermore, the mutation did not affect the
      voltage-dependent inactivation. We therefore conclude that there is no evidence
      in favour of an extracellular nucleotide-binding site in pI(Cln).

PMID- 9599003
TI  - Acceleration of virus-induced apoptosis by tumor necrosis factor.
AB  - The multiplication of vesicular stomatitis virus in HeLa cells was inhibited by
      treating the cells with tumor necrosis factor (TNF). Comparison of the kinetics
      of virus multiplication and that of virus-induced apoptosis in the TNF-treated
      cells revealed that the antiviral effect of TNF is accompanied by a rapid
      induction of apoptosis in the cells upon infection, suggesting that TNF can
      inhibit virus multiplication by accelerating an apoptotic response in the
      infected cells.

PMID- 9599002
TI  - Topological localization of cysteine 74 in the GABA transporter, GAT1, and its
      importance in ion binding and permeation.
AB  - Xenopus oocytes expressing the GABA transporter GAT1 were exposed to membrane
      impermeant sulfhydryl reagents, resulting in decreased GABA transport current,
      decreased capacitive charge movements, and increased Na+ and Li+ leakage
      currents. Mutation of cysteine 74 to alanine (C74A) eliminated these effects. The
      W68S and W68L mutations significantly increased and decreased the transporter's
      sensitivity, respectively, to sulfhydryl reagents. At each of the positions 73
      through 76, cysteine residues were accessible to external MTSET. These findings,
      together with recent evidence placing the HD2-HD3 loop on the extracellular side,
      suggest that the HD2 region does not traverse the membrane.

PMID- 9599004
TI  - Expression of Hex mRNA in early murine postimplantation embryo development.
AB  - The onset of Hex expression and its role in early murine development was analyzed
      using in situ hybridization. Hex mRNA was first detected in the chorion of the
      ectoplacental cavity and weakly at the visceral endoderm of the future yolk sac
      at embryonic age (E) 7.5. Expression in embryonic tissues was detected
      exclusively in the hepatic anlage and thyroid primordium at E 9.5. At E 12.5 and
      E 15.5, Hex expression persisted in the fetal liver and thyroid, and was also
      detected in the fetal lung. These results suggest that Hex has its role in
      differentiation and/or organogenesis of several embryonic tissues.

PMID- 9599005
TI  - Very-long-chain acyl-CoA dehydrogenase subunit assembles to the dimer form on
      mitochondrial inner membrane.
AB  - This paper describes the process of dimer assembly of mitochondrial very-long
      chain acyl-CoA dehydrogenase (VLCAD) subunit. Mature VLCAD is a homodimer of a 70
      kDa protein associated with the mitochondrial membrane. Newly synthesized VLCAD
      was present as a monomer and the major fraction was associated with the
      mitochondrial inner membrane. The association of VLCAD subunit with the
      mitochondrial membrane was observed early during dimer formation. In contrast, a
      VLCAD monomeric mutant S583W, a novel mutation identified from a patient with
      VLCAD deficiency, did not associate with the mitochondrial membrane after import
      and the major fraction remained in the mitochondrial matrix. These results
      suggest that association of VLCAD protein with mitochondrial inner membrane is
      necessary for dimer assembly and formation of mature VLCAD.

PMID- 9599006
TI  - Regulation of capsular polysialic acid biosynthesis by N-acetyl-D-mannosamine, an
      intermediate of sialic acid metabolism.
AB  - N-Acetyl-D-mannosamine (ManNAc) is a specific substrate for the synthesis of N
      acetylneuraminic acid, the essential precursor of bacterial capsular polysialic
      acid (PA). When Escherichia coli K92 used ManNAc as a carbon source, we observed
      a dramatic reduction (up to 90%) in in vivo PA production. Experiments in which
      the carbon source was changed revealed that the maximal inhibitory effect
      occurred when this sugar was present in the medium before the logarithmic phase
      of bacterial growth had started. Enzymatic analysis revealed that high
      concentrations of ManNAc-6-phosphate inhibit NeuAc lyase, the enzyme that
      synthesizes NeuAc for PA biosynthesis in E. coli. These results indicate that
      ManNAc-6-phosphate is able to regulate NeuAc lyase activity and modulate the PA
      synthesis.

PMID- 9599007
TI  - Activation of two types of brain glutamate dehydrogenase isoproteins by
      gabapentin.
AB  - The stimulatory effects of gabapentin on the activities of two types of glutamate
      dehydrogenase (GDH) isoproteins homogeneously purified from bovine brain have
      been studied at various conditions. When the effects of different gabapentin
      concentrations on GDH activities were studied in the direction of reductive
      amination of 2-oxoglutarate with NADPH as a coenzyme, a marked activation was
      observed for both isoproteins, whereas both isoproteins showed activation to a
      lesser extent with NADH as a coenzyme. Stimulatory effects of gabapentin on GDH
      activities in the direction of the oxidative deamination of glutamate were also
      observed, but to a much lesser extent than reductive amination. There were big
      differences between the two GDH isoproteins in their sensitivity to the action of
      gabapentin. The largest activation was observed with GDH II when NADPH was used
      as a coenzyme. Half-maximal stimulation was reached at around 1.5 mM. Gabapentin
      relieved the inhibition of GDH isoproteins by GTP and this resulted in an
      increase in the apparent activation by gabapentin in the presence of GTP. 2
      Oxoglutarate was found to give rise to high substrate inhibition and gabapentin
      reduced the substrate inhibition in the presence of 0.2 mM NADH. Since there are
      neurodegenerative disorders in which GDH activity is decreased, the therapeutic
      modulation of the activity of this enzyme may be clinically useful.

PMID- 9599008
TI  - HPLC determination of photosynthetic pigments during greening of etiolated barley
      leaves. Evidence for the biosynthesis of chlorophyll a'.
AB  - The temporal evolution of pigment composition during greening of etiolated barley
      leaves was investigated by reversed-phase HPLC with particular attention to
      chlorophyll (Chl) a' (C13(2) epimer of Chl a), which had been detected by
      ourselves in photosystem (PS) I particles. At early stages of greening, the Chl
      a'/Chl a molar ratio rapidly increased to a level more than twice that in mature
      leaves, then gradually leveled off, accompanied by a growth of the Chl b/Chl a
      ratio, to the mature level. After 3 h of illumination, the temporal evolution of
      the Chl a'/Chl a molar ratio nearly paralleled that of the P700/Chl a ratio with
      a stoichiometry Chl a'/P700 approximately equal to 2: this strongly suggests that
      Chl a' is biosynthesized as a constituent of the PS I reaction center complex.

PMID- 9599009
TI  - Sequence and 3D structural relationships between mammalian Ras- and Rho-specific
      GTPase-activating proteins (GAPs): the cradle fold.
AB  - An extensive study of both sequence and recent 3D structural data concerning
      GTPase interacting domains of Ras- and Rho-specific GTPase-activating proteins
      (GAPs) shows that these two subfamilies share a same 3D scaffold and are thus
      related to each other. This relationship has heretofore remained undetected
      although these domains of similar size are both totally alpha-helical and
      activate nearly structurally identical targets (Ras and Rho proteins). In this
      report, sequence similarities correlated to 3D structures of p120rasGAP and
      p50rhoGAP were detected using the sensitive two-dimensional method hydrophobic
      cluster analysis (HCA). These patterns were further extended to other members in
      each subfamily and the geometry orientation of crucial arginines R789 in p120 and
      R282 in p50 and of important stabilizing residues like p120R903 and p50N391 was
      confirmed. This overall structural relationship is centered on an invariant motif
      of three consecutive helices that we suggest to name the 'cradle fold'. This
      observation opens new perspectives to understand how small GTPases are
      specifically regulated.

PMID- 9599010
TI  - The mongoose acetylcholine receptor alpha-subunit: analysis of glycosylation and
      alpha-bungarotoxin binding.
AB  - The mongoose AChR alpha-subunit has been cloned and shown to be highly homologous
      to other AChR alpha-subunits, with only six differences in amino acid residues at
      positions that are conserved in animal species that bind alpha-bungarotoxin
      (alpha-BTX). Four of these six substitutions cluster in the ligand binding site,
      and one of them, Asn-187, forms a consensus N-glycosylation site. The mongoose
      glycosylated alpha-subunit has a higher apparent molecular mass than that of the
      rat glycosylated alpha-subunit, probably resulting from the additional
      glycosylation at Asn-187 of the mongoose subunit. The in vitro translated
      mongoose alpha-subunit, in a glycosylated or non-glycosylated form, does not bind
      alpha-BTX, indicating that lack of alpha-BTX binding can be achieved also in the
      absence of glycosylation.

PMID- 9599011
TI  - Stability and functionality of cysteine-less F(0)F1 ATP synthase from Escherichia
      coli.
AB  - All 21 native cysteines in the Escherichia coli F(0)F1 ATP synthase were replaced
      by alanines. In isolated E. coli membranes, ATP-dependent proton pumping,
      turnover of ATP hydrolysis and steady-state transition state thermodynamic
      parameters of the cysteine-less enzyme were similar to wild-type. The cysteine
      less enzyme was solubilized in n-octyl beta-D-glucopyranoside, purified by
      affinity chromatography, and reconstituted into pre-formed liposomes made from E.
      coli lipids. The properties of the reconstituted, purified enzyme were not
      significantly different from the membranous enzyme. These data demonstrate that
      cysteine-less F(0)F1 is biochemically stable and has functionality similar to
      wild-type.

PMID- 9599012
TI  - Increased cellular resistance to oxidative stress by expression of cyanobacterium
      catalase-peroxidase in animal cells.
AB  - To exploit prokaryotic antioxidant enzymes for protection of animal cells from
      oxidative damage, we expressed catalase-peroxidase of cyanobacterium
      Synechococcus PCC 7942 in 104C1 cells. The gene for this enzyme was inserted into
      the mammalian expression vector pRc/CMV. The stable transfectants obtained had
      higher specific activities of catalase and as a result became more resistant to
      H2O2 or paraquat than the parental cells. Subcellular fractionation and
      immunoblot analysis revealed that the expressed catalase-peroxidase was confined
      to the cytosol; this localization may be the basis for the effective protection
      of the transfectants from the oxidative cell damage.

PMID- 9599013
TI  - 1,25-Dihydroxyvitamin D3 inhibits tenascin-C expression in mammary epithelial
      cells.
AB  - Tenascin-C is an extracellular matrix protein with growth-, invasion- and
      angiogenesis-promoting activities. Tenascin-C is upregulated in breast carcinoma
      and stromal cells, and in many other cell types during tumorigenesis. We
      demonstrate that tenascin-C RNA expression is inhibited by 1,25-dihydroxyvitamin
      D3 (1,25-D3) in a variety of mouse and human mammary epithelial cell lines
      exhibiting normal or malignant phenotype. In EpH4 cells, the inhibition is
      maximum 24 h after 1,25-D3 treatment and correlates with a dose-dependent
      reduction in the synthesis of tenascin-C protein. Furthermore, 1,25-D3 also
      abolishes the induction of tenascin-C by serum or the tumor promoter 12-O
      tetradecanoyl phorbol 13-acetate. The inhibition of tenascin-C expression may be
      relevant for the anticancer activity of 1,25-D3.

PMID- 9599014
TI  - HAP1-huntingtin interactions do not contribute to the molecular pathology in
      Huntington's disease transgenic mice.
AB  - HAP1 (huntingtin associated protein) has previously been found to interact with
      huntingtin (htt) in a glutamine length dependent manner and has been proposed to
      play a role in the cell specific neurodegeneration observed in Huntington's
      disease (HD). We have isolated mouse HAP1 (hap1) and have shown that expression
      is not enriched in areas specifically affected in HD. We have used the yeast two
      hybrid system to demonstrate that htt amino acids 171-230 are necessary for the
      hap1-htt binding and that hapl does not interact with the transgene exon 1
      protein in a transgenic model of HD.

PMID- 9599015
TI  - Adrenomedullin production is correlated with differentiation in human leukemia
      cell lines and peripheral blood monocytes.
AB  - We demonstrated that adrenomedullin (AM) is produced and secreted from human
      leukemia cell lines (THP-1 and HL-60) as well as peripheral blood granulocytes,
      lymphocytes, monocytes and monocyte-derived macrophages. Immunoreactive AM
      accumulated in the culture media of THP-1 and HL-60 cells increased according to
      their differentiation into macrophage-like cells. Retinoic acid exerted
      synergistic effects on AM secretion from THP-1 and HL-60 cells when administered
      with tumor necrosis factor-alpha, lipopolysaccharide or 12-O-tetradecanoyl
      phorbol-13-acetate. AM was shown to increase the scavenger receptor activity on
      THP-1 cells. Thus, monocytes/macrophages should be recognized as sources of AM,
      and the secreted AM may modulate the function of macrophages.

PMID- 9599016
TI  - Genomic organization and chromosomal localization of the human peroxisomal
      membrane protein-1-like protein (PXMP1-L) gene encoding a peroxisomal ABC
      transporter.
AB  - The cDNA of the peroxisomal membrane protein-1-like protein (PXMP1-L, synonyms:
      PMP69, P70R), a novel peroxisomal ATP binding cassette transporter of yet unknown
      function, has recently been cloned. The best known peroxisomal member of this
      protein family is the adrenoleukodystrophy protein, defects of which are the
      underlying cause of X-linked adrenoleukodystrophy (X-ALD). Here we describe the
      complete exon-intron structure (19 exons and 18 introns covering 16.0 kb) of the
      human PXMP1-L gene, transcript variants, the localization on chromosome 14q24 by
      cytogenetic analysis and sequencing of the putative promoter region. PXMP1-L has
      been proposed to play a role as a modifier in determining the phenotypic
      variations observed in X-ALD. The data presented will enable sequence analysis of
      the PXMP1-L gene in X-ALD patients and facilitate the analysis of PXMP1-L
      function.

PMID- 9599017
TI  - GlcNAc-terminated glycodendrimers form defined precipitates with the soluble
      dimeric receptor of rat natural killer cells, sNKR-P1A.
AB  - Synthetic GlcNAc-terminated thiourea-bridged glycoclusters were found to be
      potent inhibitors of binding of the soluble dimeric receptor of rat natural
      killer cells, sNKR-P1A protein, to its high affinity ligand. Moreover, we have
      shown here that characteristic precipitation curves can be recorded upon mixing
      of the GlcNAc glycoclusters with sNKR-P1A. For the GlcNAc8 glycocluster the
      precipitation curve is biphasic, with high affinity and low affinity precipitates
      differing in their sensitivity towards GlcNAc-mediated inhibition of
      precipitation. Quantitative analyses of the precipitates indicate the occurrence
      of a single sugar binding site per sNKR-P1A subunit, and lead to a model of the
      most possible spatial arrangements of the glycocluster-receptor lattices. These
      results provide new tools for further studies on carbohydrate recognition by NKR
      P1A.

PMID- 9599019
TI  - Examination of temperature-induced 'gel-sol' transformation of alpha
      actinin/cross-linked actin networks by static light scattering.
AB  - We studied the gel-sol transformation of F-actin/alpha-actinin solutions. Cross
      linking of actin filaments by alpha-actinin shows a temperature-dependent
      increase in light scatter signal, (I)T. Higher F-actin/alpha-actinin molar
      ratios, r(A alpha) as well as increases in F-actin concentration, [A], and
      reduction of actin filament lengths, rAG, augment the maximal light intensity, I
      and shift the gel-sol transition point, Tg to higher temperatures. This behavior
      is interpreted in terms of the model developed by Tempel, M., Isenberg, G. and
      Sackmann, E. (1996) (Physical Review E 54, 1802-1810) based on the percolation
      theory. Using the temperature-dependent binding model of this theory allows
      instant prediction of the equilibrium constant, K for F-actin/alpha-actinin
      solutions at temperatures T < Tg.

PMID- 9599018
TI  - The regulation of phosphorylation of tau in SY5Y neuroblastoma cells: the role of
      protein phosphatases.
AB  - In Alzheimer disease brain the microtubule associated protein (MAP) tau is
      abnormally hyperphosphorylated. The role of protein phosphatases (PP) in the
      regulation of phosphorylation of tau was studied in undifferentiated SY5Y cells.
      In cells treated with 10 nM okadaic acid (OA), a PP-2A/PP-1 inhibitor, the PP-1
      and -2A activities decreased by 60% and 100% respectively and the activities of
      MAPKs, cdc2 kinase and cdk5, but not of GSK-3, increased. OA increased the
      phosphorylation of tau at Thr-231/Ser-235 and Ser-3961404, but not at Ser-262/356
      or Ser-199/202. An increase in tyrosinated/detyrosinated tubulin ratio, a
      decrease in the microtubule binding activities of tau, MAP1b and MAP2, and cell
      death were observed. Treatment with 1 microm taxol partially inhibited the cell
      death. These data suggest (1) that OA induced hyperphosphorylation of tau is
      probably the result of activated MAPK and cdks in addition to decreased PP-2A and
      PP-1 activities and (2) that in SY5Y cells the OA induced cell death is
      associated with a decrease in stable microtubules.

PMID- 9599020
TI  - Retinal dehydrogenase gene expression in stomach and small intestine of rats
      during postnatal development and in vitamin A deficiency.
AB  - Retinal dehydrogenase (RALDH) catalyzes the oxidation of retinal to all-trans and
      9-cis retinoic acid, which function as ligands controlling RAR and RXR nuclear
      receptor-signaling pathways. We have recently shown the expression of RALDH
      transcript in the stomach and small intestine by reverse transcription polymerase
      chain reaction [Bhat, P.V., Labrecque J., Dumas, F., Lacroix, A. and Yoshida, A.
      (1995) Gene 166, 303-306]. We have examined RALDH expression in the stomach and
      small intestine before and during postnatal development and in vitamin A
      deficiency by assaying for mRNA levels and protein as well as for enzyme
      activity. In -2 day fetuses, RALDH expression was high in the small intestine,
      whereas RALDH protein was not detectable in the stomach. However, expression of
      RALDH was seen in the stomach after birth, and gradually increased with age and
      reached the highest level at postnatal day 42. In the intestine, RALDH expression
      decreased postnatally. Vitamin A deficiency up-regulated RALDH expression in the
      stomach and small intestine, and administration of retinoids down-regulated the
      RALDH expression in these tissues. These results show the differential expression
      of RALDH in the stomach and small intestine during postnatal development, and
      that vitamin A status regulates the expression of RALDH gene in these tissues.

PMID- 9599021
TI  - Effects of the Kupffer cell inactivator gadolinium chloride on rat liver oxygen
      uptake and content of mitochondrial cytochromes.
AB  - The effect of gadolinium chloride (GdCl3) on the content of rat liver
      mitochondrial cytochromes was investigated in relation to the basal rate of O2
      uptake and Kupffer cell functioning, assessed in liver perfusion studies. (1) A
      single dose of GdCl3 (10 mg/kg) produced a significant diminution in Kupffer cell
      functioning, evidenced by the decreases in colloidal carbon uptake and in carbon
      induced O2 uptake observed at 6-24 h after treatment, without changes in the
      sinusoidal lactate dehydrogenase efflux as index of tissue viability; at 48 h
      after GdCl3 administration, carbon phagocytosis was recovered to control values,
      whereas carbon-induced O2 uptake remained lower than control values. (2) GdCl3
      also caused a 34% decrease in the basal rate of O2 consumption of the liver at 24
      h after treatment, which returned towards control values at 48 h. (3) The content
      of mitochondrial cytochromes c1 and c at 24 h after GdCl3 treatment was
      significantly reduced by 40 and 32%, respectively, which returned to control
      values at 48 h, without changes in that of cytochromes b and a+a3. It is
      concluded that GdCl3-induced decrease in liver O2 consumption is a reversible
      phenomenon that seems to be due to a diminution in the content of mitochondrial
      cytochromes c1 and c.

PMID- 9599022
TI  - A cosmid and cDNA fine physical map of a human chromosome 13q14 region frequently
      lost in B-cell chronic lymphocytic leukemia and identification of a new putative
      tumor suppressor gene, Leu5.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is a human hematological neoplastic
      disease often associated with the loss of a chromosome 13 region between RB1 gene
      and locus D13S25. A new tumor suppressor gene (TSG) may be located in the region.
      A cosmid contig has been constructed between the loci D13S1168 (WI9598) and
      D13S25 (H2-42), which corresponds to the minimal region shared by B-CLL
      associated deletions. The contig includes more than 200 LANL and ICRF cosmid
      clones covering 620 kb. Three cDNAs likely corresponding to three different genes
      have been found in the minimally deleted region, sequenced and mapped against the
      contigged cosmids. cDNA clone 10k4 as well as a chimeric clone 13g3, codes for a
      zinc-finger domain of the RING type and shares homology to some known genes
      involved in tumorigenesis (RET finger protein, BRCA1) and embryogenesis (MID1).
      We have termed the gene corresponding to 10k4/13g3 clones LEU5. This is the first
      gene with homology to known TSGs which has been found in the region of B-CLL
      rearrangements.

PMID- 9599023
TI  - Genomic organization and promoter characterization of human CXCR4 gene.
AB  - CXCR4 is the receptor for the CXC chemokine SDF1 that has essential functions on
      embryo organogenesis, immunological functions and T lymphocyte trafficking.
      Recently, CXCR4 has drawn unexpected attention as it was recently identified as a
      co-factor required for entry of lymphotropic HIV isolates in CD4+ T lymphocytes.
      CXCR4 is the only SDF1 receptor identified so far. This suggests that CXCR4
      expression is critical for the biological effects of SDF1. To investigate the
      mechanisms controlling both the constitutive and induced expression of CXCR4
      receptors we have isolated and characterized the promoter region and determined
      the genomic structure of the human gene. The CXCR4 gene contains two exons
      separated by an intronic sequence. A 2.6 kb 5'-flanking region located upstream
      the CXCR4 open reading frame contains a TATA box and the transcription start site
      characteristic of a functional promoter. This region also contains putative
      consensus binding sequences for different transcription factors, some of them
      associated with the hemopoiesis and lymphocyte development.

PMID- 9599024
TI  - Genomic structure and chromosomal location of the human TGFbeta-receptor
      interacting protein-1 (TRIP-1) gene to 1p34.1.
AB  - The human TRIP-1 (transforming growth factor-beta (TGBbeta)-receptor interacting
      protein-1) cDNA encodes a protein able to associate specifically with the type II
      TGFbeta receptor. It is phosphorylated on serine and threonine by this receptor
      kinase which makes it a strong candidate as part of the TGFbeta signal
      transduction pathway. We have isolated the genomic sequence of TRIP-1 and found
      that the complete coding region is organised into 11 exons ranging from 39 to 397
      bp and spanning approximately 9 kb of genomic DNA. The 5' flanking region lacks a
      TATA box but is GC-rich, suggesting that it is a constitutively expressed gene
      which is in agreement with its wide pattern of expression. Fluorescence in situ
      hybridisation mapped the TRIP-1 gene to chromosome 1p34.1 whereas a pseudogene is
      located on chromosome 7q32.

PMID- 9599025
TI  - Cloning and analysis of a novel human putative DNA methyltransferase.
AB  - DNA methylation is intricately involved in a variety of cellular processes, such
      as differentiation, cell cycle progression, X-chromosome inactivation and genomic
      imprinting. However, little is known about how specific DNA methylation patterns
      are established and maintained. Previously one mammalian DNA methyltransferase
      has been described, but there has been considerable speculation about the
      presence of a second activity capable of methylation. Here we report the
      identification and characterization of a novel human putative DNA
      methyltransferase. Using a bioinformatics screen we have identified several
      expressed sequence tags which show high sequence similarity to the
      Schizosaccharomyces pombe gene pmt1+. The cDNA for PuMet (for putative DNA
      methyltransferase) was cloned and the predicted amino acid sequence deduced. The
      gene is ubiquitously expressed, albeit at low levels. Like several other DNA
      methyltransferases, the bacterially overexpressed protein is not active in
      methylation assays.

PMID- 9599026
TI  - A novel method for surface modification to promote cell attachment to hydrophobic
      substrates.
AB  - The ability to study and regulate cell behavior at a biomaterial interface
      requires strict control over material surface chemistry. Perhaps the greatest
      challenge to researchers working in this area is preventing the fouling of a
      given surface due to uncontrolled protein adsorption. This work describes a
      method for coupling peptides to hydrophobic materials for the purpose of
      simultaneously preventing nonspecific protein adsorption and controlling cell
      adhesion. A hexapeptide containing the ubiquitous RGD cell-adhesion motif was
      coupled to polystyrene (PS) via a polyethylene oxide (PEO) tether in the form of
      a modified PEO/PPO/PEO triblock copolymer. Triblocks were adsorbed onto PS at a
      density of 3.3 +/- (5.14 x 10(-4)) mg/m2 (1.4 x 10(5) +/- 2.12 x 10(1)
      molecules/microm2), which was determined by isotope 125I labeling. The peptide,
      GRGDSY, was activated at the N terminus with N-Succinimidyl 3-(2-pyridyldithio)
      propionate and coupled to immobilized triblocks where the terminal hydroxyls had
      been converted to sulfhydryl groups. Surface peptide density was measured by
      amino acid analysis and found to be 1.4 x 10(4) +/- 0.47 x 10(4)
      molecules/microm2. PS modified with PEO/PPO/PEO copolymers alone was found to be
      inert to cell adhesion both in the presence of serum proteins and when exposed to
      activated RGD peptide. In contrast, PS conjugated with RGD via endgroup-activated
      PEO/PPO/PEO copolymers supported cell adhesion and spreading. The surface
      coupling scheme reported here should prove valuable for studying cell-ligand
      interactions under simplified and highly controlled conditions.

PMID- 9599027
TI  - Collagen/apatite coating on 3-dimensional carbon/carbon composite.
AB  - A three-dimensional carbon/carbon composite (3D C/C) was studied as potential
      bone-repairing material; its major mechanical properties were found to be closer
      to those of human bone than other common bone-repairing materials available. In
      vitro calcification tests revealed that as-received 3D C/C is almost bioinert in
      simulated body fluid (SBF) over an immersion period of 4 weeks. To improve the
      bioactivity of 3D C/C, surface modification was accomplished through two
      practical routes: (1) grafting with polyethylene glycol (PEG) and (2)
      phosphorylation and precalcification. After grafting with alpha, omega
      di(aminopropyl) polyethylene glycol 800 (NH2-PEG-NH2), a continuous layer of
      calcium phosphate was formed on the surface of 3D C/C in SBF after 4 weeks.
      Phosphorylated 3D C/C samples have the ability to induce apatite precipitation
      after precalcification in a saturated Ca(OH)2 solution for 1 week. To speed up
      the coating process, a calcification solution with collagen was developed in
      which a collagen/apatite coating layer can be formed on 3D C/C in 9 h in ambient
      conditions.

PMID- 9599028
TI  - Repassivation of titanium and surface oxide film regenerated in simulated
      bioliquid.
AB  - The change in potential during repassivation of titanium in artificial bioliquids
      was examined, and the regenerated surface oxide film on titanium was
      characterized using X-ray photoelectron spectroscopy and Auger electron
      spectroscopy to elucidate the repassivation reaction of titanium in a biological
      system. The repassivation rate in Hanks' solution was slower than that in saline
      and was not influenced by the pH of the solution. This indicates that more
      titanium ions dissolve in a biological system than hitherto was predicted when
      the surface film is destroyed. Phosphate ions are taken up preferentially in the
      surface film during regeneration, and the film consists of titanium oxide and
      titanium oxyhydroxide containing titanium phosphate. Calcium ions and phosphate
      ions are adsorbed by the film after regeneration, and calcium phosphate or
      calcium titanium phosphate is formed at the outermost surface. Ions constituting
      Hanks' solution other than calcium and phosphate were absent from the surface
      oxide.

PMID- 9599029
TI  - Viscoelastic properties of demineralized human dentin measured in water with
      atomic force microscope (AFM)-based indentation.
AB  - Using an atomic force microscope (AFM) with an attachment specifically designed
      for indentation, we measured the mechanical properties of demineralized human
      dentin under three conditions: in water, in air after desiccation, and in water
      after rehydration. The static elastic modulus (E(h)r = 134 kPa) and viscoelastic
      responses (tau(epsilon) = 5.1 s and tau(sigma) = 6.6 s) of the hydrated,
      demineralized collagen scaffolding were determined from the standard linear solid
      model of viscoelasticity. No significant variation of these properties was
      observed with location. On desiccation, the samples showed considerably larger
      elastic moduli (2 GPa), and a hardness value of 0.2 GPa was measured. Upon
      rehydration the elastic modulus decreased but did not fully recover to the value
      prior to dehydration (381 kPa).

PMID- 9599030
TI  - In vitro sister chromatid exchange induced by glass ionomer cements.
AB  - The genotoxicity of three glass ionomer cements used in dentistry, manufactured
      by American (Vitrebond), Japanese (Fuji I), and European (Ketac Cem) companies
      were examined. The cement components were mixed according to the manufacturers'
      instructions and allowed to set for two defined times: 1 h or 1 week, before
      extracting them, as established by ISO standard 10993 part 12. To highlight
      sister chromatid exchange during mitosis, the extracts then were tested with
      human peripheral lymphocytes in the presence or absence of metabolic activation
      with S9 mix. The test performed was a genotoxicity test as provided for in
      standard EN 30993 part 3. Vitrebond resulted in direct genotoxicity and was
      strongly cytotoxic both in the extracts performed at 1 h and those at 1 week if
      they were allowed to set without photoactivation. Fuji I was noncytotoxic and
      showed only uncertain indirect genotoxicity in the extracts at 1 h; genotoxicity
      was not present in the extracts at 1 week. Ketac Cem cement was not genotoxic nor
      was it cytotoxic either at 1 h or 1 week. The authors concluded that of the three
      cements tested the European cement Ketac Cem passed one of the tests suggested by
      the EEC standard for assessing genotoxicity.

PMID- 9599031
TI  - Effects of fibrin micromorphology on neurite growth from dorsal root ganglia
      cultured in three-dimensional fibrin gels.
AB  - The effect of fibrin matrix micromorphology on neurite growth was investigated by
      measuring the length of neurites growing in three-dimensional fibrin gels with
      well characterized micromorphologies. Dorsal root ganglia (DRGs) from 7-day chick
      embryos were entrapped and cultured in gels made from varying concentrations of
      fibrinogen (5-15 mg/mL) or calcium (2-10 mM). The length of growing neurites was
      measured with light videomicroscopy, and the number and diameter of fibrin fiber
      bundles were measured from scanning electron micrographs. An increase in
      fibrinogen concentration caused a decrease in the average fiber bundle thickness,
      an increase in the number of fiber bundles, and a marked decrease in neurite
      length. Gels made with different calcium concentrations had a similar range of
      variation in fibrin fiber bundle number or diameter, but these variations had
      little effect on neurite and associated nonneuronal cell outgrowth. These results
      provide insights into the process of neurite advance within fibrin and may be
      useful in the design of fibrin-based materials used for peripheral nerve
      regeneration. Furthermore, this study provides the first detailed experimental
      data on the micromorphology of fibrin matrices made from more than 5 mg/mL of
      fibrinogen and indicates that existing kinetic models of fibrin polymerization do
      not accurately predict fibrin structure at these higher concentrations.

PMID- 9599032
TI  - Growth hormone-loaded macroporous calcium phosphate ceramic: in vitro
      biopharmaceutical characterization and preliminary in vivo study.
AB  - Calcium phosphate ceramics recently have been used for administering therapeutic
      agents in bone. The present work investigated the efficacy of macroporous
      biphasic calcium phosphate (MBCP) implants as a matrix for local delivery of
      human growth hormone (hGH). An initial study showed that the release of 5 microg
      of hGH loaded onto MBCP cylinders was rapid during the first 48 h and sustained
      for a total of 11 days. The biological integrity of hGH (88.2%) was checked using
      a specific bioassay (cellular proliferation of hGH-sensitive Nb2 cells) in
      comparison with a radioimmunoassay to calculate the proportion of bioactive hGH
      released. MBCP cylinders then were loaded with 1, 10, and 100 microg of hGH and
      implanted into rabbit femurs (n = 16) to determine hGH effects on bone ingrowth
      and ceramic resorption, as evaluated by scanning electron microscopy and image
      analysis. Results indicated that hGH increased bone ingrowth and ceramic
      resorption significantly in comparison with contralateral and control implants.
      Biochemical parameters monitored in rabbit plasma showed that hGH did not produce
      detectable systemic effects. Thus the use of MBCP appears to be effective for
      local delivery of hGH and for increasing bone ingrowth.

PMID- 9599033
TI  - Fibroblast growth factor-2 alters the effect of eroding polylactide-polyglycolide
      on osteogenesis in the bone chamber.
AB  - The effects of recombinant human fibroblast growth factor-2 (rhFGF-2) in the
      presence of eroding 50:50 poly(DL-lactide-co-glycolide) (PDLLG) on acute bone
      healing were studied in the optical bone chamber (BCI). BCIs were loaded with
      disks of PDLLG surrounded by one of four rhFGF-2 doses. Fifty-two female rabbit
      right tibias were implanted. Commencing the third week post implantation (W3)
      healing in the BCI compartment was observed weekly, using intravital microscopy,
      until W8. The doses were: unloaded, loaded with polymer only, and polymer plus
      0.5, 1.0, and 10 microg rhFGF-2. Videotaped and photographed bone images were
      measured and analyzed using a frame-grabber digitizing system. Comparison with
      controls revealed that ossification rates were significantly above normal in
      rabbits loaded with polymer plus any of the rhFGF-2 doses. Comparison with
      polymer-only BCIs showed that PDLLG plus any of the three rhFGF-2 doses was
      linked with ossification rates significantly higher than baseline. The results
      indicated that FGF-2 in the dose range studied effectively can overcome the
      retarding effects of eroding polymer on ossification that has been reported by
      this laboratory. Interpretation of the retarding effects of the polymer disks,
      although consistent with previously studied washer-shaped devices of the same
      material, was complicated by a difference in erosion rate. This result supports
      the notion that erodible device geometry is a major factor in determining
      biocompatibility and must be considered in the design of carriers. Accordingly,
      programming of dose specificity for delivering a given polypeptide cytokine to a
      given host site must allow for the inhibitory effects of an eroding carrier and
      the influence of device geometry on these effects and erosion.

PMID- 9599034
TI  - Prevention of calcification of glutaraldehyde-crosslinked porcine aortic cusps by
      ethanol preincubation: mechanistic studies of protein structure and water
      biomaterial relationships.
AB  - Clinical usage of bioprosthetic heart valves (BPHVs) fabricated from
      glutaraldehyde-pretreated porcine aortic valves is restricted due to
      calcification-related failure. We previously reported a highly efficacious
      ethanol pretreatment of BPHVs for the prevention of cuspal calcification. The aim
      of the present study is to extend our understanding of the material changes
      brought about by ethanol and the relationship of these material effects to the
      ethanol pretreatment anticalcification mechanism. Glutaraldehyde-crosslinked
      porcine aortic valve cusps (control and ethanol-pretreated) were studied for the
      effects of ethanol on tissue water content and for spin-lattice relaxation times
      (T1) using solid state proton NMR. Cusp samples were studied for protein
      conformational changes due to ethanol by ATR-FTIR spectroscopy. The changes in
      cuspal tissue-cholesterol (in vitro) interactions also were studied. Cusp
      material stability was assessed in terms of residual glutaraldehyde content and
      collagenase degradation. Water content of the cusp samples was decreased
      significantly due to ethanol pretreatment. The cuspal collagen conformational
      changes (per infrared spectroscopy) brought about by ethanol pretreatment were
      persistent even after rat subdermal implantation of cusp samples for 7 days. In
      vitro cholesterol uptake by cusps was greatly reduced as a result of ethanol
      pretreatment. Ethanol pretreatment of cusps also resulted in increased resistance
      to collagenase digestion. Cuspal glutaraldehyde content was not changed by
      ethanol pretreatment. We conclude that ethanol pretreatment of bioprosthetic
      heart valve cusps causes multi-component effects on the tissue/material and
      macromolecular characteristics, which partly may explain the ethanol-pretreatment
      anticalcification mechanism.

PMID- 9599035
TI  - Engineering the tissue which encapsulates subcutaneous implants. II. Plasma
      tissue exchange properties.
AB  - This study assesses the plasma-tissue exchange characteristics of the capsular
      tissue that forms around implants and how they are affected by implant porosity.
      The number of vessels and their permeability to rhodamine were measured by
      intravascular injection of the fluorophore tracer into Sprague-Dawley rats that
      hosted for 3-4 months polyvinyl alcohol (PVA) and polytetrafluoroethylene (PTFE)
      subcutaneous implants. Rats were implanted with four pore sizes of PVA--a
      nonporous PVA (PVA-skin), and 5, 60, and 700 micron mean pore sizes (PVA-5, PVA
      60, and PVA-700, respectively)--and two pore sizes of PTFE: 0.50 (PTFE-0.5) and
      5.0 (PTFE-5) mean micron pore sizes. Photodensitometric image analysis was used
      to quantify the local tracer extravasation and, hence the permeability
      coefficients of isolated vessels around the implants. The number of functional
      vessels within 100 microm of the implants highlighted by the lissamine-rhodamine
      tracer were counted with fluorescence microscopy and with H&E stained sections
      using brightfield microscopy. The permeability of vessels did not vary
      substantially with implant pore size but generally were lower than those measured
      for surrounding subcutis. Pore size, however, had a dramatic effect on the
      vascular density of tissue-encapsulating implants: the number of microvessels
      (under 10 microm in radius) within the tissue surrounding the porous implants was
      higher than the number around nonporous implants. Pore sizes on the order of
      cellular dimensions incited optimal neovascularization; the vascular density
      around PVA-60 implants was six times higher (p < .001) and three times higher (p
      < .001) than those around PVA-0 implants in the fluorescent images and in
      brightfield, respectively. Moreover, brightfield microscopy showed the number of
      vessels around PVA-60 implants was almost double those in normal subcutis. The
      results suggest that optimal vascular density around long-term implants, such as
      sensors, biofluid cell constructs, and immunoisolated cell systems, may be
      engineered with pore size.

PMID- 9599036
TI  - Engineering the tissue which encapsulates subcutaneous implants. III. Effective
      tissue response times.
AB  - The results of two previous studies have shown that implant porosity can be used
      to increase both the measured diffusion coefficients and the vascularity within
      the tissue encapsulating long-term subcutaneous implants. This study investigates
      the hypothesis that the analyte concentrations within the tissue surrounding
      porous implants will respond more quickly to changes in plasma levels than does
      the densely packed, avascular fibrous capsule surrounding nonporous implants. The
      average concentration of lissamine-rhodamine was measured in tissue within 100
      microm of the following implants at four different times following injection of
      the tracer: PVA-skin, PVA-5, PVA-60, PVA-700 (polyvinyl alcohol nonporous, 5
      microm, 60 microm, and 700 microm mean pore sizes, respectively) and PTFE-0.5 and
      PTFE-5 (polytetrafluoroethylene 0.5 microm and 5 microm mean pore sizes,
      respectively). The results were compared to those of unimplanted subcutaneous
      tissue (SQ). In addition, the data were analyzed with a simple two-compartment
      model in which a tissue response time constant (taup) was extracted. As in the
      case of vascular density, the cellular dimension of the PVA-60 pore sizes
      produced surrounding tissue with the optimum response times to changes in plasma
      concentrations. The concentrations of rhodamine within the tissue surrounding the
      PVA-60 implant were the highest at all time points and responded to the change in
      plasma rhodamine concentration approximately three times more quickly (taup = 764
      s) than the fibrous tissue encapsulating the nonporous PVA-skin (taup = 2058 s)
      and more than twice as quickly as SQ (taup = 1627 s). The overall mass transfer
      rate between plasma and the tissue surrounding the different implants calculated
      from the permeability and density of vessels from the previous study correlated
      very well (r2 = 0.7, p < .02, slope of 0.98) with the reciprocal of the tissue
      response time constant (taup).

PMID- 9599037
TI  - In vitro influence of apatite-granule-specific area on human growth hormone
      loading and release.
AB  - Although calcium phosphate biomaterials often are used as drug delivery systems
      (DDS) at bone sites, the conditions affecting the loading of the therapeutic
      agent (TA) have not been well documented. A human growth hormone (hGH) adsorption
      method was used in this study to investigate the influence of the formulated
      apatite (AP)-specific area on loading and release. AP powders were formulated
      with a 200-500 microm granulometry and various specific areas. Two milligrams of
      hGH in solution were deposited for 24 h at 37 degrees C on 100 mg of AP with
      different specific areas. The amount of hGH loaded was determined by
      immunoradiometric assay (IRMA) and eluted stain bioassay (ESTA) using Nb2
      lymphoma rat cells. Although loading was not greatly influenced by a specific
      area between 3 and 25 m2/g, dependency was noted for higher specific areas. Human
      GH release was measured by IRMA and ESTA over a 33-day period, with half-time
      release between 25 and 79 h. Comparison of IRMA and ESTA measurements for the hGH
      amounts loaded showed that hGH biologic activity was conserved. Results indicate
      that it is feasible to control the quantity of TA loading on AP by modifying
      specific areas for in vivo applications.

PMID- 9599038
TI  - Osteogenic protein (OP-1, BMP-7) stimulates cartilage differentiation of human
      and goat perichondrium tissue in vitro.
AB  - The objective of this study was to examine in vitro the influence of recombinant
      human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7)] on
      cartilage formation by human and goat perichondrium tissue containing progenitor
      cells with chondrogenic potential. Fragments of outer ear perichondrium tissue
      were embedded in clotting autologous blood to which rhOP-1 had been added or not
      added (controls), and the resulting explant was cultured for 3 weeks without
      further addition of rhOP-1. Cartilage formation was monitored biochemically by
      measuring [35S]-sulphate incorporation into proteoglycans and histologically by
      monitoring the presence of metachromatic matrix with cells in nests. The presence
      of rhOP-1 in the explant at the beginning of culture stimulated [35S]-sulphate
      incorporation into proteoglycans in a dose-dependent manner after 3 weeks of
      culture. Maximal stimulation was reached at 40 microg/mL (human explants: +148%;
      goat explants: +116%). Histology revealed that explants treated with 20-200
      microg/mL of rhOP-1, but not untreated control explants, contained areas of
      metachromatic-staining matrix with chondrocytes in cell nests. It was concluded
      that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue.
      The direct actions of rhOP-1 on perichondrium cells in the stimulation of
      chondrocytic differentiation and production of cartilage matrix in vitro provides
      a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo.
      Thus rhOP-1 may promote early steps in the cascade of events leading to cartilage
      formation and could prove to be an interesting factor in the regeneration of
      cartilage in articular cartilage defects.

PMID- 9599039
TI  - Polymer surface chemistry and a novel attachment mechanism in corneal epithelial
      cells.
AB  - The initial attachment reaction of most cultured cell types to polymers is based
      on a linkage of integrin receptors to serum-derived fibronectin and vitronectin
      that adsorb onto the polymer surface. Recently isolated corneal epithelial cells
      have an additional attachment mechanism, known to operate on tissue culture
      polystyrene, which involves endogenous protein synthesis and an intact system of
      microtubules. Here, we determine if this novel attachment mechanism is operative
      on polymers of different surface chemistries. The attachment, growth, and
      deposition of basement membrane proteins by corneal epithelial cells was compared
      on two hydrophilic surfaces (tissue culture polystyrene and Primaria) and one
      relatively hydrophobic surface (unmodified polystyrene). Superior levels of cell
      attachment were found on the hydrophilic polymers, but cells also attached
      effectively to the hydrophobic surface. Growth rates showed that the cells were
      able to overcome the differential effects of polymer surface chemistry during a 7
      day time period. Polymer surface chemistry had subtle effects on the temporal
      pattern of biosynthesis of extracellular matrix proteins likely to be involved in
      cell adhesion. These results show that effective attachment and growth can occur
      on a hydrophobic polymer when corneal epithelial cells use the endogenous
      attachment mechanism.

PMID- 9599040
TI  - Novel thermally reversible hydrogel as detachable cell culture substrate.
AB  - A novel UV crosslinkable co-polymer of 4-(N-cinnamoylcarbamide)methylstyrene
      (CCMS) and N-isopropylacrylamide (IPAAm) was partially entrapped in traditional
      tissue-culture-treated polystyrene and crosslinked by UV light irradiation.
      Dishes modified by this method showed a change in contact angle with respect to
      temperature as compared to tissue culture polystyrene controls. Surface chemical
      analysis indicated that the crosslinked hydrogel does not detach from the surface
      after successive rinsing in ethanol and water, keeping the cells or cell
      construct free of unwanted soluble polymer after detachment. Cultures of both
      bovine endothelium and human retinal pigmented epithelium were confirmed to be
      able to attach and grow on the polymer-modified surfaces morphologically
      identical to that on control tissue culture polystyrene surfaces. Corresponding
      to a change in temperature, these cultures would detach and could be transplanted
      to another culture surface without functional and structural changes. These
      results show that the new, photo-crosslinkable hydrogel system can utilize the
      hydrophobic/hydrophilic change of the surface for cell culture detachment while
      being permanently applicable to any tissue culture geometry.

PMID- 9599041
TI  - Vibrational spectroscopic study of tetracalcium phosphate in pure polycrystalline
      form and as a constituent of a self-setting bone cement.
AB  - Polycrystalline tetracalcium phosphate (TTCP), a material of considerable
      interest for human implantation due to its similarity to hydroxyapatite, was
      studied by means of Raman and FT-IR spectroscopy. The spectra were interpreted on
      the basis of group theoretical considerations. In addition, the setting reaction
      of a calcium phosphate cement (CPC) consisting of an equimolar mixture of TTCP
      and dicalcium phosphate (DCPA) was investigated by Raman spectroscopy. The band
      of the totally symmetric phosphate mode v1 of TTCP showed marked factor group
      splittings. The splitting components arose at coincident wave numbers in the IR
      and Raman spectra. This observation was in accordance with space group P2(1)
      (factor group C2(2), Z = 4). The characteristic splitting of v1 allowed the
      setting reaction of CPC to hydroxyapatite to be followed. According to the Raman
      spectroscopic results, considerable amounts of TTCP must be present at the sample
      surface after 24 h of setting in an aqueous environment.

PMID- 9599042
TI  - Effect of surface treatment on unalloyed titanium implants: spectroscopic
      analyses.
AB  - Surgical implant finishing and sterilization procedures were investigated to
      determine surface characteristics of unalloyed titanium (Ti). All specimens
      initially were cleaned with phosphoric acid and divided into five groups for
      comparisons of different surface treatments (C = cleaned as above, no further
      treatment; CP = C and passivated in nitric acid; CPS = CP and dry-heat
      sterilized; CPSS = CPS and resterilized; CS = C and dry-heat sterilized). Auger
      (AES), X-ray photoelectron (XPS), and Raman spectroscopic methods were used to
      examine surface compositions. The surface oxides formed by all treatments
      primarily were TiO2, with some Ti2O3 and possibly TiO. Significant concentrations
      of carbonaceous substances also were observed. The cleaning procedure alone
      resulted in residual phosphorus, primarily as phosphate groups along with some
      hydrogen phosphates. A higher percentage of physisorbed water appeared to be
      associated with the phosphorus. Passivation (with HNO3) alone removed phosphorus
      from the surface; specimens sterilized without prior passivation showed the
      thickest oxide and phosphorus profiles, suggesting that passivation alters the
      oxide characteristics either directly by altering the oxide structure or
      indirectly by removing moieties that alter the oxide. Raman spectroscopy showed
      no crystalline order in the oxide. Carbon, oxygen, phosphorus, and nitrogen
      presence were found to correlate with previously determined surface energy.

PMID- 9599043
TI  - Influence of thrombus components in mediating Staphylococcus aureus adhesion to
      polyurethane surfaces.
AB  - The role of protein and cellular components of thrombi in mediating bacterial
      adhesion on artificial surfaces was investigated in this study. The attachment of
      Staphylococcus aureus on polyurethane surfaces was observed directly using an
      automated video microscopy system. Surfaces were preconditioned with components
      of platelet-fibrin thrombi, including fibrinogen, thrombin, plasma, and isolated
      platelets. Experiments were performed in a radial flow chamber, and attachment
      rate constants were compared on the preconditioned surfaces in an effort to
      understand the complex relationship that exists between bacterial infection and
      thrombosis on synthetic biomaterials. Preadsorption of fibrinogen to surfaces
      significantly increased S. aureus adhesion compared to those preadsorbed with
      albumin alone while the presence of fibrin dramatically increased bacterial
      attachment compared to plasma preadsorbed surfaces. While the presence of
      adherent platelets also increased bacterial attachment, fibrin appeared to play a
      larger role in mediating bacterial adhesion on polyurethane surfaces. Striking
      results were obtained on the zwitterionic phosphonated polyurethane for a number
      of pretreatment conditions with regard to decreased bacterial adhesion and
      fibrinogen deposition.

PMID- 9599044
TI  - Web alert. Oncogenes and cell proliferation.

PMID- 9599045
TI  - [Proceedings of the 5th Congress of Tropical Medicine of the French Languages.
      Mauritius, 18-20 November 1996].

PMID- 9599046
TI  - Improvements needed in cervical screening in England.

PMID- 9599047
TI  - Report calls for action on antibiotic resistance.

PMID- 9599048
TI  - Space mission aims to increase understanding of the nervous system.

PMID- 9599049
TI  - Flawed immunisation policies in India led to polio paralysis.

PMID- 9599050
TI  - Biodiversity loss threatens new treatments.

PMID- 9599051
TI  - Carers of patients receiving palliative care. Specialized psychosocial care may
      be needed for carers.

PMID- 9599052
TI  - New combined hepatitis A and B vaccine. Immunisation is only part of preventing
      infectious disease.

PMID- 9599053
TI  - New combined hepatitis A and B vaccine. New vaccine is an adjunct, not an
      alternative to preventive behaviours.

PMID- 9599054
TI  - Deaths related to intrapartum asphyxia. Consultant expansion in obstetrics and
      gynaecology is not fast enough.

PMID- 9599055
TI  - Deaths related to intrapartum asphyxia. Denominators are needed before
      conclusions can be drawn.

PMID- 9599056
TI  - Deaths related to intrapartum asphyxia. Intrapartum death rates in England 1993-5
      did not show consistent peaks or troughs.

PMID- 9599057
TI  - New government, same narrow vision. Medical profession must change things itself.

PMID- 9599058
TI  - New government, same narrow vision. Health authorities in New Zealand have spin
      doctors to produce good news.

PMID- 9599059
TI  - New government, same narrow vision. Most New Zealanders believe their public
      health service has deteriorated.

PMID- 9599060
TI  - Doctors should beware of asking for too high a salary. What is too high a salary?

PMID- 9599061
TI  - Is Africa near to collapse?

PMID- 9599062
TI  - Network news. Signaling a trend, Tenet-SmithKline deal links California hospital
      labs.

PMID- 9599064
TI  - 10th International Symposium on Supportive Care in Cancer. San Antonio, Texas,
      USA. 11-14 March 1998. Abstracts.

PMID- 9599063
TI  - Vestibular bibliography.

PMID- 9599065
TI  - Maximizing the utility of HIV patient observational databases. Proceedings of a
      symposium. Amsterdam, The Netherlands, August 24, 1996.

PMID- 9599066
TI  - Computer-assisted decision program for antimicrobial therapy raises quality of
      care, lowers costs.

PMID- 9599067
TI  - From Hypertension to Heart Failure. Symposium proceedings. Stockholm, Sweden,
      January 1997.

PMID- 9599068
TI  - Rethinking the evaluation and priorities in telemedicine.

PMID- 9599069
TI  - Telemicrobiology: feasibility study.
AB  - BACKGROUND: Rural hospitals generally lack staffing with infectious disease
      specialists or pathologists. Without on-site pathologists, the range of
      microbiology services offered by clinical laboratories may be limited as well.
      OBJECTIVE: To study the feasibility of using static-image telepathology to
      evaluate Gram stains of microbiologic preparations. MATERIALS AND METHODS: In
      this retrospective feasibility study, three pathologists evaluated Gram stains of
      slides from 50 cases by two viewing modalities: static-image telepathology and
      conventional light microscopy. Digital video images of slides were captured at
      two magnifications (using 40x and 100x objective lenses) at 1024 x 768 x 24-bit
      color and transmitted over standard telephone lines at 14,400 kbps. Pathology
      reports and culture results served as "truth diagnoses." Categories of
      interpretations were correct, minor discrepancy, or major discrepancy with regard
      to the implications for patient care. RESULTS: The diagnostic accuracy of video
      image readings and conventional light microscopy readings were nearly identical,
      with no statistically significant differences in the performances of specialty
      and nonspecialty pathologists (P > 0.05). The mean accuracies of readings of the
      video images and light microscopy images were 95.3% and 95.4%, respectively.
      Taking into account the time required by a referring pathologist to capture video
      digital images, telemicrobiology was somewhat less efficient than conventional
      light microscopy. CONCLUSIONS: Pathologists can accurately evaluate digital video
      images of preselected fields on Gram-stained slides. In clinical practice,
      however, a limiting factor may be the availability of local personnel qualified
      to select the microscopic fields for evaluation by telepathologists. The adequacy
      of the video images suggests that telepathology may also be used for remote
      supervision of quality assurance programs in microbiology laboratories, as well
      as for remote proficiency training of laboratory personnel.

PMID- 9599070
TI  - Applications of telemedicine in the United States space program.
AB  - Since the beginning of human space flight, NASA has been placing humans in
      extreme and remote environments. There are many challenges in maintaining humans
      in outer space, including the provision of life-support systems, radiation
      shielding, and countermeasures for minimizing the effect of microgravity. Because
      astronauts are selected for their health, among other factors, disease and
      illness are minimized. However, it is still of great importance to have
      appropriate medical care systems in place to address illness and injury should
      they occur. With the exception of the Apollo program, exploration of space has
      been limited to missions that are within several hundred miles of the surface of
      the Earth. At the drawn of the 21st century and the new millennium, human
      exploration will be focused on operation of the International Space Station (ISS)
      and preparation for human missions to Mars. These missions will present inherent
      risks to human health, and, therefore, appropriate plans must be established to
      address these challenges and risks. Crews of long-duration missions must become
      more independent from ground controllers. New systems, protocols, and procedures
      are currently being perfected. Application of emerging technologies in
      information systems and telecommunications will be critical to inflight medical
      care. Application of these technologies through telemedicine will provide crew
      members access to information, noninvasive procedures for assessing health
      status, and guidance through the integration of sensors, holography, decision
      support systems, and virtual environments. These technologies will also serve as
      a basis to enhance training and medical education. The design of medical care for
      space flight should lead to a redesign of the practice of medicine on Earth.

PMID- 9599071
TI  - A proposed framework for economic evaluation of telemedicine.
AB  - Economic evaluation of telemedicine compares the costs and other consequences of
      delivering specific services through telemedicine vs. alternative means. Cost
      effectiveness analysis, the most common method used for health issues, helps to
      assess whether the expected health benefits are worth the investment.
      Telemedicine raises particular challenges for evaluators: a telemedicine system
      may have multiple uses and joint costs that are difficult to apportion to one
      service, the existence of a system may lead to expanded indications for use, and
      technological change may rapidly make an evaluation outdated. Public and private
      regulation and payment may affect the diffusion of telemedicine. Uncertainty
      surrounds the policy of the U.S. Food and Drug Administration, which is still
      formulating its position. Changes are underway in policies on licensure and
      credentialing of clinicians, which have traditionally been done by state and by
      site, to reflect the fact that telemedicine services may cross these regional
      boundaries. Lack of insurance coverage for telemedicine services has been
      considered an impediment to adoption with fee-for-service payment. Under
      capitation payment and fixed budgets, however, providers have financial
      incentives to use the most efficient method to deliver services, and these
      arrangements would favor telemedicine if it is the less costly alternative. If
      telemedicine were most costly and the health benefits worth the cost, monitoring
      might be needed to ensure the quality of care.

PMID- 9599072
TI  - Telemedicine in border area of China.

PMID- 9599073
TI  - Telemedicine using a desktop conference system (Phoenix) in Kyushu, Japan.
AB  - OBJECTIVE: The Kyushu area of southwestern Japan has several mountains and 157
      inhabited islands. We assessed the feasibility of implementing a desktop
      conference (DTC) system to improve medical care in this area. TELECOMMUNICATIONS
      TECHNOLOGY AND EQUIPMENT: The Phoenix DTC system (NTT Corporation, Tokyo, Japan)
      for personal computers includes a microphone, speaker, color CCD camera, and
      appropriate software. We used a digital camera for still pictures and image
      analysis software for radiographs and CT and MRI films. The system was installed
      on a Pentium 133 MHz computer, which was connected by ISDN line at a 128 kbps
      data rate to a clinic on a small island where one physician cares for 1000
      residents, two small nursing offices where each nurse tends 100 residents, two
      nursing homes, a hospital in a mountainous area, and the residence of a patient
      with atopic dermatitis. Connections were made once a week for a period of 6
      months. RESULTS: The transmitted still pictures; e.g., senile nevus, atopic
      dermatitis, chickenpox, and a radiograph of a suspected fracture, were useful for
      diagnosis and clinical decision making. We received and responded to inquiries
      from residents of the participating nursing homes on nutrition, senile
      depression, nevus, decubitus ulcers, urinary tract infection, and protection
      against Legionella infection. We also used the system to deliver lectures on
      pediatrics to nurses; provided case discussions on diaphragmatic herniation and
      subtentorial tumor; and had on-line presentation of a patient with beta
      thalassemia using presentation software. CONCLUSION: The DTC system used in the
      present study seemed technically satisfactory and useful in improving medical
      care in remote sites of Japan.

PMID- 9599074
TI  - Financial analysis of savings from telemedicine in Ohio's prison system.
AB  - The Ohio Department of Rehabilitation and Corrections (ODRC) implemented a
      telemedicine pilot project in March of 1995. The project brought together the
      Southern Ohio Correctional facility in Lucasville, the Corrections Medical Center
      in Columbus, and The Ohio State University Medical Center, also located in
      Columbus. Its purpose was to evaluate the use of two-way interactive video for
      the delivery of health services. With two-way interactive video, physicians in
      one location established audio and video links with inmates hundreds of miles
      away. Data were collected on the potential savings as a result of telemedicine
      usage in the Ohio prison system. Costs associated with telemedicine and those
      incurred without telemedicine were determined on per-consult basis for
      comparison. The cost for a medical consult to be performed at the Corrections
      Medical Center averaged $263.51 per inmate. The cost for a medical consult via
      telemedicine varied from month to month, depending on the utilization volume. The
      ODRC experienced savings for telemedicine usage when 129 or more consults were
      performed each quarter. During the third quarter, 145 telemedicine consults were
      performed. The cost per consult for telemedicine usage during this quarter was
      $255.19. There was a savings of $8.48 per consult, resulting in a quarterly
      savings of $1206. As the utilization of telemedicine continued to increase in the
      fourth quarter, the amount of savings increased.

PMID- 9599075
TI  - Reliability of telemedicine in evaluating skin tumors.
AB  - OBJECTIVES: To determine the reliability of videoconferencing technology in
      evaluating skin tumors, the impact of the technology on the clinicians' degree of
      suspicion that a skin tumor is malignant, and the recommendation to do a biopsy.
      MATERIALS AND METHODS: Four skin cancer screenings were conducted at rural health
      care facilities in eastern North Carolina that were connected to East Carolina
      University School of Medicine. A dermatologist saw the patients in person at the
      local facility, and the same patient was seen by a dermatologist via a T-1
      connection to Greenville, North Carolina. RESULTS: The two physicians were in
      absolute agreement on 59% of the 107 skin tumors evaluated. There were five
      lesions identified by the on-site dermatologist as a probable or definite
      malignancy. The degree of concern about a lesion being malignant and the decision
      whether to do a biopsy were not significantly different, as shown by kappa
      analysis. CONCLUSION: The concern about the malignancy of a particular skin
      lesion and the recommendation whether to do a biopsy were not significantly
      affected by telemedicine technology.

PMID- 9599076
TI  - Telemedicine should never be a substitute for training.

PMID- 9599077
TI  - The value of bone marrow biopsy for the diagnosis of amyloidosis secondary to
      tuberculosis.

PMID- 9599078
TI  - [Breast cancer susceptibility gene BRCA1 of hereditary breast cancer/ ovarian
      cancer syndrome].

PMID- 9599079
TI  - Finding patients for clinical trials.

PMID- 9599080
TI  - Analysis of pufferfish homologues of the AT-rich human APP gene.
AB  - Mutations in the beta-amyloid precursor protein (APP) gene are associated with
      some forms of Familial Alzheimer's Disease. The human APP gene is large, the 19
      exons span approximately 300 kb, and AT-rich, at 40% GC. We have examined the
      genomic structure and cDNA sequence of the APP gene in the pufferfish Fugu
      rubripes and Tetraodon fluviatilis, respectively. In contrast to human, the Fugu
      APP gene spans less than 10 kb of DNA, with the introns compacted 48-fold on
      average. Two axons, alternatively processed in humans, are absent in both
      pufferfish. APP is the largest, most AT-rich gene examined in Fugu and is also
      the most highly compressed. The genomic sequences spanning the human and the Fugu
      APP genes were analysed with a set of exon and gene prediction programs. Results
      show that these are highly reliable for the Fugu gene with lower false positive
      and false negative rates than are seen in the analysis of the human gene.
      Comparative analysis of Fugu sequences homologous to very AT-rich regions in the
      human genome may, therefore, be advantageous in gene-finding efforts, both for
      their highly reduced sizes and their reliable gene predictions.

PMID- 9599081
TI  - Structure of a genome region of the Lactobacillus gasseri temperate phage phiadh
      covering a repressor gene and cognate promoters.
AB  - By sequencing the DNA regions which flank the intG gene encoding integrase of the
      temperate Lactobacillus (Lb.) gasseri bacteriophage phiadh, a continuous sequence
      of 6590 bp was established. It encompasses five newly identified ORFs, of which
      four are located upstream, and one (orfC) downstream of intG. Proteins
      corresponding to the expected products of the intG upstream coding regions, orfA
      (33 kDa), orf2 (14 kDa), rad (12.1 kDa), and tec (7.9 kDa), were identified by in
      vitro expression of subcloned DNA fragments. Rad shares homology with
      transcription regulators, including SinR of Bacillus species and the repressor of
      phage phi105. The gporf2 is similar to predicted products of topologically
      equivalent coding regions of the Lactococcus lactis phage TP901-1 and the B.
      subtilis phage phi105. Promoters for the divergently oriented rad and tec genes
      were mapped within the 435-bp region between them and specify overlapping
      transcripts with extended 5'-untranslated sequences. As shown with lacZ fusions,
      Rad repressed transcription from the tec and rad promoters 20- and 5-fold,
      respectively. In Lb. gasseri, weak expression of cloned rad ws sufficient to
      mediate immunity towards phiadh.

PMID- 9599082
TI  - [Labor in women with heart and great vessel diseases].
AB  - The way of termination of pregnancy was retrospectively analysed in 95 pregnant
      women with heart and/or great vessels diseases, hospitalised in years 1989-1991
      and 1995-1996 in the Department of Obstetrics and Perinatology of Pomeranian
      Medical Academy. The condition of cardiovascular system was assessed according to
      NYHA classification on admission and just before delivery with participation of
      an experienced cardiologist. Kind of heart disease, mode and period of delivery,
      perinatal cardiovascular symptoms, duration of delivery and duration of
      hospitalisation, weight and clinical condition of the newborns were taken under
      consideration. In more than half of cases (60%) cesarean sections were performed.
      Among the indications for elective cesarean section cardiological indications
      formed the dominant group (29.5%). During perinatal period deterioration of
      circulatory system sufficiency associated with increase of number of cesarean
      sections were observed.

PMID- 9599083
TI  - [The efficiency of goiter prevention due to iodine deficiency in pregnant women].
AB  - The iodine is indispensable element for life that is also fundamental substract
      for thyroid hormone synthesis which make very important influence on protein's
      lipid's, carbohydrate's and highly caloric substances metabolism and are a
      requisite of proper man development. The pregnant women are one of population
      group which is the most sensitive on iodine's deficiency. The results of
      researches indicate on insufficient iodine intake in pregnant women diet, whose
      take food even according to diet's recommendation given by physician. The wide
      iodine's prophylaxis which was provided as yet is insufficient in case of
      pregnant and nursing women. It is confirmed the necessity of additional iodine
      supplementation. A set of control tests should be done in requires cases that
      inform physician about changes in function and size of thyroid gland and make
      possible the individualization of treatment. The supplementation doses of iodine
      about 150 micrograms are safe and there was not observed any side effects during
      their taking.

PMID- 9599084
TI  - [Large-scale screening for early diagnosis of gestational diabetes mellitus
      (GDM)].
AB  - The aim of study was to evaluate incidence of GDM in Poland. All 1500 pregnant
      women between 24-28 week's gestation consulted in 4 centers were offered a 50 g
      oral glucose test (screening test). Capillary blood glucose was measured at 60
      min after glucose ingestion. When blood glucose > 140 mg/dl, 75 g OGTT according
      to WHO criteria was performed. 241 women have abnormal screening test and in 181
      cases blood glucose were at range 140-160 mg/dl, in 39 at range 160-180 and 21
      were > 180 mg/dl. Only 14 women in the first group (140-160 mg/dl) have diagnosed
      GDM (7.7%). In second group 24 pregnant women have GDM (61.5%). Overall GDM
      incidence is shown to be 3.7% (57 women). The mean age for the GDM was 28.8 +/-
      0.9 years compared with 26.4 +/- 0.4 years (p < 0.05) uncomplicated pregnancy.

PMID- 9599085
TI  - [The evaluation of the efficiency of treatment in ectopic pregnancy with the
      application of various surgical procedures].
AB  - In our study we analyzed 54 women with confirmed diagnosis of ectopic pregnancy,
      in whom two different surgical approaches were performed. There were 40
      salpingotomies and 14 salpingectomies. The dynamics of the decrease of beta hCG
      serum level were assessed. The beta hCG levels not greater than 5 mIU/ml (2nd IS)
      were the markers of the recovery. Similar therapeutic effect was obtained in both
      testing group. The normalisation of the beta hCG serum level was observed after
      19th and 21st days after salpingectomy and salpingotomy, respectively.

PMID- 9599086
TI  - [The use of color Doppler ultrasonography in the diagnosis of benign breast
      tumors].
AB  - The paper describes Color Doppler Velocity (CDV) technique with clinical
      implications in examinations of patients with benign breast lesions. Results
      suggest that CDV might be useful in differentiation of the breast lesions in
      routine clinical work.

PMID- 9599087
TI  - [The use of biodegradable valtrac-bar rings for intestinal anastomosis in
      advanced ovarian cancer patients].
AB  - Intestinal anastomoses using Valtrac-Bar biofragmentable rings were performed in
      9 advanced ovarian cancer patients presenting with symptoms of acute or subacute
      intestinal obstruction. Two ileo-transversal anastomoses, six sigmo-rectal and
      one ileo-ileal ones were performed. A part of sigmoid colon with tumour causing
      obstruction was resected in seven patients and in two patients a resection of an
      ileal loop was performed. In two patients a colostomy was necessary. The result
      of anastomosis with Valtrac-Bar was satisfactory in all patients: no cases of
      peritonitis, anastomosis leak or fistulae were observed. The treatment of
      intestinal obstruction allowed for a prolongation and improvement of quality of
      life of these patients and enabled further treatment with chemotherapy. We
      conclude that biofragmentable Valtrac-Bar ring is a safe and effective device
      enabling easy and fast intestinal anastomosis even in patients with inappropriate
      healing.

PMID- 9599088
TI  - [The role of apoptosis of granulosa cells in follicular atresia].
AB  - Apoptosis plays an important role in the process of morphogenesis and
      embryogenesis. Its increase or inhibition is an etiopathological factor in many
      different diseases. It has recently been shown that apoptosis of granulosa cells
      is one of the main mechanisms responsible for follicular atresia. There are many
      other factors influencing the process of granulosa cells apoptosis, among them
      the most important are: RnGH, FSH, LH, sex hormones (estrogens and androgens),
      growth factors and their receptors (EGF/TGF-alpha, FGF, IGF-1) and cytokines
      (e.g. TNF-alpha). The article presents data concerning the regulatory mechanisms
      of granulosa cells apoptosis in the ovary.

PMID- 9599089
TI  - [Catamenial pneumothorax during menstruation].
AB  - Recurring pneumothorax associated with menstruation was named catamenial
      pneumothorax. Proposed causes for catamenial pneumothorax include allows air to
      enter the peritoneal cavity via the genital tract, prostaglandins, diaphragmatic
      fenestrations and systemic endometriosis. In this article, we review the
      literature experience with this entity and critically assess treatment options
      based on pathophysiology mechanism.

PMID- 9599090
TI  - [Leiomyoma of small intestine in patient treated for ovarian tumor].
AB  - Small intestinal tumors are relatively rare, and notoriously difficult to
      diagnose. In our case 64 years old female was operated because suspicion of
      ovarian tumor. The complained on recurrent gastrointestinal bleeding. An
      arteriogram of superior mesenteric artery revealed arteriovenous malformation in
      the distal part of small intestine. Then the solid mass near the right ovary was
      discovered by sonographic and gynecological examination. Hence the patient was
      operated in the gynecological ward. We found female reproductive organs looking
      normally. There were solid tumor 6 x 10 cm growing up from the jejunum. The tumor
      and the part of jejunum was resected. The histological examination confirmed the
      diagnosis of leiomyoma. The healing was normal and the patient went home 12 days
      after surgery.

PMID- 9599091
TI  - [Endometrial changes in the ovaries during full-term pregnancy: a case report].
AB  - The authors described case of 27 years old female patient treated due to
      infertility of unknown etiology. The female was pregnant after series of
      intrauterine insemination. During caesarean section due to pelvic longitudinal
      lie the chocolate cyst and endometriosis of the ovary were found. The authors did
      not find any information in the literature about coincidence of endometriosis of
      female reproductive organs and full-term pregnancy.

PMID- 9599092
TI  - Syndromic management of sexually transmitted diseases in developing countries:
      what role in the control of the STD and HIV epidemics?

PMID- 9599093
TI  - Satisfaction may not suffice! A commentary on 'A patient's perspective'.

PMID- 9599094
TI  - Behavior Therapy and Research Society. Roster of Clinical Fellows-1997.

PMID- 9599095
TI  - Varicella supplement 1998 and consensus guidelines for management. United Kingdom
      Advisory Group on Chickenpox.

PMID- 9599096
TI  - [Molecular biology and molecular genetics in otorhinolaryngology-- carcinogenesis
      and tumor suppressor genes].

PMID- 9599097
TI  - Bayliss, myogenic tone and volume-regulated chloride channels in arterial smooth
      muscle.

PMID- 9599098
TI  - [Prevention of hospital transmission of tuberculosis].

PMID- 9599099
TI  - Symposium in honor of Claude Amiel. Physiology and Pathophysiology of Epithelial
      Transport. Paris, France, 12-13 September 1997.

PMID- 9599100
TI  - [Progress in surgery of stomach cancer].

PMID- 9599101
TI  - [Expression of facilitative glucose transporter mRNA in human myocardium].

PMID- 9599102
TI  - Dynamic regulation of copper uptake and detoxification genes in Saccharomyces
      cerevisiae.
AB  - The essential yet toxic nature of copper demands tight regulation of the copper
      homeostatic machinery to ensure that sufficient copper is present in the cell to
      drive essential biochemical processes yet prevent the accumulation to toxic
      levels. In Saccharomyces cerevisiae, the nutritional copper sensor Mac1p
      regulates the copper-dependent expression of the high affinity Cu(I) uptake genes
      CTR1, CTR3, and FRE1, while the toxic copper sensor Ace1p regulates the
      transcriptional activation of the detoxification genes CUP1, CRS5, and SOD1 in
      response to copper. In this study, we characterized the tandem regulation of the
      copper uptake and detoxification pathways in response to the chronic presence of
      elevated concentrations of copper ions in the growth medium. Upon addition of
      CuSO4, mRNA levels of CTR3 were rapidly reduced to eightfold the original basal
      level whereas the Ace1p-mediated transcriptional activation of CUP1 was rapid and
      potent but transient. CUP1 expression driven by an Ace1p DNA binding domain
      herpes simplex virus VP16 transactivation domain fusion was also transient,
      demonstrating that this mode of regulation occurs via modulation of the Ace1p
      copper-activated DNA binding domain. In vivo dimethyl sulfate footprinting
      analysis of the CUP1 promoter demonstrated transient occupation of the metal
      response elements by Ace1p which paralleled CUP1 mRNA expression. Analysis of a
      Mac1p mutant, refractile for copper-dependent repression of the Cu(I) transport
      genes, showed an aberrant pattern of CUP1 expression and copper sensitivity.
      These studies (i) demonstrate that the nutritional and toxic copper
      metalloregulatory transcription factors Mac1p and Ace1p must sense and respond to
      copper ions in a dynamic fashion to appropriately regulate copper ion homeostasis
      and (ii) establish the requirement for a wild-type Mac1p for survival in the
      presence of toxic copper levels.

PMID- 9599104
TI  - A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable
      angina.
AB  - BACKGROUND: Activation of platelets is central to the pathophysiology of unstable
      angina. We studied whether inhibition of the final common pathway for platelet
      aggregation with tirofiban, a nonpeptide glycoprotein IIb/IIIa receptor
      antagonist, would improve clinical outcome in this condition. METHODS: In a
      double-blind study, we randomly assigned 3232 patients who were already receiving
      aspirin to additional treatment with intravenous tirofiban for 48 hours. The
      primary end point was a composite of death, myocardial infarction, or refractory
      ischemia at 48 hours. RESULTS: The incidence of the composite end point was 32
      percent lower at 48 hours in the group that received tirofiban (3.8 percent, vs.
      5.6 percent with heparin; risk ratio, 0.67; 95 percent confidence interval, 0.48
      to 0.92; P=0.01). Percutaneous revascularization was performed in 1.9 percent of
      the patients during the first 48 hours. At 30 days, the frequency of the
      composite end point (with the addition of readmission for unstable angina) was
      similar in the two groups (15.9 percent in the tirofiban group vs. 17.1 percent
      in the heparin group, P=0.34). There was a trend toward a reduction in the rate
      of death or myocardial infarction with tirofiban (a rate of 5.8 percent, as
      compared with 7.1 percent in the heparin group; risk ratio, 0.80; 95 percent
      confidence interval, 0.61 to 1.05; P=0.11), and mortality was 2.3 percent, as
      compared with 3.6 percent in the heparin group (P=0.02). Major bleeding occurred
      in 0.4 percent of the patients in both groups. Reversible thrombocytopenia
      occurred more frequently with tirofiban than with heparin (1.1 percent vs. 0.4
      percent, P=0.04). CONCLUSIONS: Tirofiban was generally well tolerated and, as
      compared with heparin, reduced ischemic events during the 48-hour infusion
      period, during which revascularization procedures were not performed. The
      incidence of refractory ischemia and myocardial infarction was not reduced at 30
      days, but mortality was lower among the patients given tirofiban. Platelet
      inhibition with aspirin plus tirofiban may have a role in the management of
      unstable angina.

PMID- 9599103
TI  - Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in
      unstable angina and non-Q-wave myocardial infarction.
AB  - BACKGROUND: Antithrombotic therapy improves the prognosis of patients with acute
      coronary syndromes, yet the syndromes remain a therapeutic challenge. We
      evaluated tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa
      receptor, in the treatment of unstable angina and non-Q-wave myocardial
      infarction. METHODS: A total of 1915 patients were randomly assigned in a double
      blind manner to receive tirofiban, heparin, or tirofiban plus heparin. Patients
      received aspirin if its use was not contraindicated. The study drugs were infused
      for a mean (+/-SD) of 71.3+/-20 hours, during which time coronary angiography and
      angioplasty were performed when indicated after 48 hours. The composite primary
      end point consisted of death, myocardial infarction, or refractory ischemia
      within seven days after randomization. RESULTS: The study was stopped prematurely
      for the group receiving tirofiban alone because of excess mortality at seven days
      (4.6 percent, as compared with 1.1 percent for the patients treated with heparin
      alone. The frequency of the composite primary end point at seven days was lower
      among the patients who received tirofiban plus heparin than among those who
      received heparin alone (12.9 percent vs. 17.9 percent; risk ratio, 0.68; 95
      percent confidence interval, 0.53 to 0.88; P=0.004). The rates of the composite
      end point in the tirofiban-plus-heparin group were also lower than those in the
      heparin-only group at 30 days (18.5 percent vs. 22.3 percent, P=0.03) and at 6
      months (27.7 percent vs. 32.1 percent, P=0.02). At seven days, the frequency of
      death or myocardial infarction was 4.9 percent in the tirofiban-plus-heparin
      group, as compared with 8.3 percent in the heparin-only group (P=0.006). The
      comparable figures at 30 days were 8.7 percent and 11.9 percent (P=0.03),
      respectively, and those at 6 months were 12.3 percent and 15.3 percent (P=0.06).
      The benefit was consistent in the various subgroups of patients and in those
      treated medically as well as those treated with angioplasty. Major bleeding
      occurred in 3.0 percent of the patients receiving heparin alone and 4.0 percent
      of the patients receiving combination therapy (P=0.34). CONCLUSIONS: When
      administered with heparin and aspirin, the platelet glycoprotein IIb/IIIa
      receptor inhibitor tirofiban was associated with a lower incidence of ischemic
      events in patients with acute coronary syndromes than in patients who received
      only heparin and aspirin.

PMID- 9599105
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 16-1998. Pneumonia and the acute respiratory distress syndrome in
      a 24-year-old man.

PMID- 9599106
TI  - Comparison of the early outcome of acute myocardial infarction in women and men.

PMID- 9599107
TI  - Comparison of the early outcome of acute myocardial infarction in women and men.

PMID- 9599108
TI  - Clinical problem-solving: refusing HIV testing.

PMID- 9599109
TI  - Clinical problem-solving: refusing HIV testing.

PMID- 9599110
TI  - Clinical problem-solving: refusing HIV testing.

PMID- 9599111
TI  - Clinical problem-solving: refusing HIV testing.

PMID- 9599112
TI  - Clinical problem-solving: refusing HIV testing.

PMID- 9599113
TI  - Therapy for hyperthyroidism and Graves' ophthalmopathy.

PMID- 9599114
TI  - Epidemic of bilateral optic neuropathy in Dar es Salaam, Tanzania.

PMID- 9599115
TI  - Vaginitis.

PMID- 9599116
TI  - Vaginitis.

PMID- 9599117
TI  - Vaginitis.

PMID- 9599118
TI  - Case 1-1998: a boy with a seizure.

PMID- 9599119
TI  - Fiddleheads and the international normalized ratio.

PMID- 9599121
TI  - [Do-it-yourself AIDS test prohibited].

PMID- 9599120
TI  - Must good HMOs go bad? First of two parts: the commercialization of prepaid group
      health care.

PMID- 9599122
TI  - [Breakthrough in AIDS therapy does not apply to children].

PMID- 9599123
TI  - [Peer review in requests for subsidies. Zorg-onderzoek Nederland].

PMID- 9599125
TI  - Secondary sexual characteristics and menses in young girls.

PMID- 9599124
TI  - [Obituary to Professor Helena Nielubowiczowa].

PMID- 9599126
TI  - Secondary sexual characteristics and menses in young girls.

PMID- 9599127
TI  - Munchausen by proxy syndrome.

PMID- 9599128
TI  - Preventing hospital admissions for asthma.

PMID- 9599129
TI  - Errors in food intake article.

PMID- 9599130
TI  - SIDS or murder?

PMID- 9599131
TI  - Pediatric emergency medicine: legal briefs.

PMID- 9599132
TI  - Proceedings of the 6th International Symposium on Molecular Aspects of
      Chemotherapy. Gdansk, Poland, July 9-12, 1997.

PMID- 9599133
TI  - The electronic Plant Gene Register.

PMID- 9599134
TI  - Letters to Jacques: selected letters of Heinz Kohut to Jacques Palaci.

PMID- 9599135
TI  - On reintegrating dissociated theories: comment on Kirsch and Lynn (1998)
AB  - In response to I. Kirsch and S.J. Lynn's (1998) review of dissociation theories
      of hypnosis, the authors discuss the role of theory in current hypnosis research.
      In addition, they show how the 2 dissociation theories, as well as an alternative
      sociocognitive theory, can be integrated into a dual-system model of action (D.A.
      Norman & T. Shallice, 1986). Finally, they argue that the essence of dissociation
      theory does not necessarily rely on special mechanisms, such as the amnesic
      barrier and hidden observer, which Kirsch and Lynn critiqued.

PMID- 9599136
TI  - Dissociating the wheat from the chaff in theories of hypnosis: Reply to Kihlstrom
      (1998) and Woody and Sadler (1998)
AB  - Although there are noteworthy commonalities among disparate theories of hypnosis,
      they are neither as readily integrated nor as complementary as J.F. Kihlstrom
      (1998) and E. Woody and P. Sadler (1998) implied. All current theories of
      hypnosis, including our social cognitive model, are provisional and incomplete,
      and each has something of value to offer. However, the multiple streams of
      consciousness hypothesis and the hypnotic state hypothesis should be abandoned
      because they are neither well supported by data nor consistent with current
      research and theory in social and cognitive psychology. In their place, the
      authors propose theoretical formulations based on such concepts as response sets,
      hierarchical control systems, associative memory networks, automatic activation
      of behavior, motivation, intention, and response expectancy.

PMID- 9599137
TI  - Bioresources and "biopiracy" in Brazil.

PMID- 9599138
TI  - Funding themselves and others.

PMID- 9599139
TI  - Gray whales in cold water.

PMID- 9599140
TI  - Counting NIH's fiscal chickens.

PMID- 9599141
TI  - Private help for a public database?

PMID- 9599142
TI  - Genome data shake tree of life.

PMID- 9599143
TI  - Genes put mammals in age of dinosaurs.

PMID- 9599144
TI  - New clue to how anthrax kills.

PMID- 9599145
TI  - 'Monogamous' gibbons really swing.

PMID- 9599146
TI  - The patenting of DNA.

PMID- 9599147
TI  - Triplet-repeat transcripts: a role for DNA in disease.

PMID- 9599148
TI  - AIDS vaccine development.

PMID- 9599150
TI  - On "The science of substance abuse".

PMID- 9599149
TI  - AIDS vaccine development.

PMID- 9599152
TI  - Plan would link, bolster health research.

PMID- 9599151
TI  - DNA sequencers' trial by fire.

PMID- 9599153
TI  - AIDS researchers negotiate tricky slopes of science.

PMID- 9599154
TI  - Writing, speech separated in split rain.

PMID- 9599155
TI  - Beam splitter teases out phase secrets.

PMID- 9599156
TI  - Technology, experimentation, and the quality of survey data.

PMID- 9599157
TI  - The era of pathway quantification.

PMID- 9599158
TI  - Biodemographic trajectories of longevity.
AB  - Old-age survival has increased substantially since 1950. Death rates decelerate
      with age for insects, worms, and yeast, as well as humans. This evidence of
      extended postreproductive survival is puzzling. Three biodemographic insights-
      concerning the correlation of death rates across age, individual differences in
      survival chances, and induced alterations in age patterns of fertility and
      mortality--offer clues and suggest research on the failure of complicated
      systems, on new demographic equations for evolutionary theory, and on fertility
      longevity interactions. Nongenetic changes account for increases in human life
      spans to date. Explication of these causes and the genetic license for extended
      survival, as well as discovery of genes and other survival attributes affecting
      longevity, will lead to even longer lives.

PMID- 9599159
TI  - Interns versus the Minister.

PMID- 9599160
TI  - [Last remedy against hog cholera remains on the shelf].

PMID- 9599162
TI  - [Hog cholera in the news].

PMID- 9599161
TI  - [Pig farmer and veterinarian: history].

PMID- 9599163
TI  - [Swallowed and impacted carp fish-hook in a dog].

PMID- 9599164
TI  - [The recent mass killing of Dutch pigs].

PMID- 9599165
TI  - [Pioneers: veterinarians from earlier times (24). Delabere Pritchett Blaine (1770
      1845)].

PMID- 9599167
TI  - [Americans study Internal Quality Control].

PMID- 9599166
TI  - [Lateral patella luxation].

PMID- 9599168
TI  - [Annual congress 1997 - theme program. Man and animal: hale and hearty].

PMID- 9599169
TI  - [Future perspective of companion animals practice (we all want to go to heaven,
      but no one wants to die!)].

PMID- 9599171
TI  - [Disinfection of footwear in cattle farming].

PMID- 9599170
TI  - [Risk for pet birds following exposure to burn products of pans coated with PTEF
      and butter].

PMID- 9599172
TI  - [The pig in politics].

PMID- 9599173
TI  - [Reproduction in horses: contagious equine endometritis (CEM)].

PMID- 9599174
TI  - [Influenza A(H5N1): current status].

PMID- 9599175
TI  - [Good veterinary practice impossible following decision Veterinary Disciplinary
      Tribunal].

PMID- 9599176
TI  - [Broad interpretation 'mortal danger'].

PMID- 9599177
TI  - [NCI? What is it? What do they do?].

PMID- 9599178
TI  - [Disciplinary Tribunal out for legal cleverness?].

PMID- 9599179
TI  - [Cystic ovarian follicles in cattle].

PMID- 9599180
TI  - [Stimulation of estrus using prostaglandins].

PMID- 9599181
TI  - [Once more hog cholera].

PMID- 9599182
TI  - [KNMvD's viewpoint of ethical questions concerning reproduction in ruminants
      (Royal Dutch Society of Veterinarians)].

PMID- 9599183
TI  - Is the management of kidney transplantation influenced by preoperative intake of
      acetylsalicylic acid?

PMID- 9599185
TI  - Proceedings of the annual meeting of the European Academy of Nutritional Sciences
      (EANS). Potsdam, September 15-16, 1995.

PMID- 9599184
TI  - Transvaginal repair of vesicovaginal fistulae.

PMID- 9599186
TI  - [14th Annual meeting of the German Association for the Study of the Liver (GASL).
      Halle, January 30-31, 1998. Abstracts].

PMID- 9599187
TI  - [Histocytochemical study of Ca2+/calmodulin-dependent protein kinase IV].

PMID- 9599188
TI  - Simple, robust linkage tests for affected sibs.
AB  - Parametric-linkage analysis applied to large pedigrees with many affected
      individuals has helped in the identification of highly penetrant genes; but, for
      diseases lacking a clear Mendelian inheritance pattern or caused by several genes
      of low to moderate penetrance, a more robust strategy is nonparametric analysis
      applied to small sets of affected relatives, such as affected sib pairs. Here we
      show that the robustness of affected-sib-pair tests is related to the shape of
      the constraint set for the sibs' identity-by-descent (IBD) probabilities. We also
      derive a set of constraints for the IBD probabilities of affected sib triples and
      use common features of the shapes of the two constrain sets to introduce new
      nonparametric tests (called "minmax" tests) that are more robust than those in
      current use. Asymptotic-power computations support the robustness of the proposed
      minmax tests.

PMID- 9599189
TI  - Approaches for Studying Neural Circuits: Application to Alcohol Research.
      Proceedings of a satellite symposium of Society for Neuroscience 26th annual
      meeting. Washington, DC, USA. November 16, 1996.

PMID- 9599190
TI  - The association of radiographically detected vertebral fractures with back pain
      and function: a prospective study.
AB  - BACKGROUND: Vertebral fractures are a hallmark of postmenopausal osteoporosis and
      an important end point in trials of osteoporosis treatment, but the clinical
      significance of these fractures remains uncertain. OBJECTIVE: To determine the
      association of new vertebral fractures with back pain and back-related functional
      limitation in older women. DESIGN: Prospective observational study. SETTING:
      Multicenter Study of Osteoporotic Fractures. PARTICIPANTS: 7223 white women aged
      65 years and older. MEASUREMENTS: Lateral spine radiographs were obtained at
      baseline and at a follow-up examination an average of 3.7 years later. Prevalent
      and incident radiographic vertebral fractures were assessed by quantitative
      morphometry. Frequency and severity of back pain, disability in doing six
      activities involving the back, and days of bed rest and days of limited activity
      due to back pain were assessed annually by questionnaire during follow-up.
      RESULTS: Among women without a vertebral fracture at baseline, those with at
      least one incident vertebral fracture were more likely to have increased back
      pain (odds ratio [OR], 2.4 [95% CI, 1.7 to 3.3]) and back disability (OR, 2.6
      [CI, 1.9 to 3.7]) and at least 1 day of bed rest due to back pain (OR, 6.7 [CI,
      4.4 to 10.2]) and 7 days of limited activity due to back pain per year (OR, 3.8
      [CI, 2.7 to 5.0]). Among women with a fracture at baseline, those with an
      incident vertebral fracture also had a greater risk for increased back pain (OR,
      2.0 [CI, 1.4 to 2.8]) and back disability (OR, 2.2 [CI, 1.5 to 3.1]) and at least
      1 day of bed rest (OR, 7.9 [CI, 4.9 to 12.9]) and 7 days of limited activity per
      year (OR, 3.5 [CI, 2.4 to 5.0]). Women with incident fracture had about 10
      additional limited-activity days and 1 to 2 days of bed rest per year. New
      vertebral fractures that did not come to medical attention were associated with
      increased back pain and functional limitation. CONCLUSION: New vertebral
      fractures, even those not recognized clinically, are associated with substantial
      increases in back pain and functional limitation due to back pain in older white
      women. Prevention of new vertebral fractures should reduce the burden of back
      pain and functional limitation in women with vertebral osteoporosis.

PMID- 9599192
TI  - Incidence of hepatitis C in patients receiving different preparations of
      hepatitis B immunoglobulins after liver transplantation.
AB  - BACKGROUND: Recurrence of hepatitis B virus (HBV) or hepatitis C virus (HCV)
      infection after liver transplantation is a clinical problem. Polyclonal
      immunoglobulins against hepatitis B surface antigen (HBIGs) prevent the
      recurrence of HBV infection, but no effective prophylaxis is available for HCV
      infection. Before screening of blood donors was introduced in France, HBIGs may
      have contained antibody to HCV (anti-HCV). OBJECTIVE: To determine the influence
      of HBIG on the occurrence of hepatitis C after liver transplantation before and
      after 1990. DESIGN: Retrospective cohort study. SETTING: Liver transplantation
      unit of a university hospital. PATIENTS: 428 consecutive patients who had liver
      transplantation because of cirrhosis between 1984 and 1994. MEASUREMENTS:
      Detection of serum HCV RNA before and 1 year after transplantation and findings
      on liver graft biopsy. RESULTS: Among the 218 patients who had HCV infection
      before transplantation, the incidence of HCV viremia after transplantation was
      lower in those receiving HBIG than in those not receiving HBIG (25 of 46 patients
      [54%] compared with 162 of 172 patients [94%]; P < 0.001). In patients receiving
      HBIG, the incidence of HCV viremia after transplantation was lower among those
      who had transplantation before March 1990 than among those who had
      transplantation after this date (15 of 33 patients [45%] compared with 10 of 13
      patients [77%]; P = 0.05). Among the 210 patients without HCV infection before
      transplantation, acquired infection was significantly less frequent in those
      receiving HBIG than in those not receiving HBIG (18 of 68 patients [26%] compared
      with 40 of 86 patients [47%]; P < 0.001). Passively transmitted anti-HCV was
      transiently detected in patients receiving HBIG before March 1990. Multivariate
      analysis in patients with HCV infection before transplantation showed that the
      absence of HBIG and transplantation after March 1990 were independent significant
      risk factors for chronic hepatitis C after transplantation. CONCLUSIONS:
      Polyclonal immunoglobulins that are treated for viral decontamination and contain
      anti-HCV could prevent HCV infection.

PMID- 9599191
TI  - Protein supplements increase serum insulin-like growth factor-I levels and
      attenuate proximal femur bone loss in patients with recent hip fracture. A
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Elderly persons who have osteoporotic hip fracture are often
      undernourished, particularly with respect to protein. Protein malnutrition may
      contribute to the occurrence and outcome of hip fracture. OBJECTIVE: To
      investigate whether oral protein supplements benefit bone metabolism in patients
      with recent hip fracture. DESIGN: 6-month, randomized, double-blind, placebo
      controlled trial with a 6-month post-treatment follow-up. SETTING: University
      orthopedic ward. PATIENTS: 82 patients (mean age, 80.7 +/- 7.4 years) with recent
      osteoporotic hip fracture. Patients received calcium supplementation, 550 mg/d,
      and one dose of vitamin D, 200,000 IU (at baseline). INTERVENTION: Protein
      supplementation, 20 g/d, or isocaloric placebo (among controls). MEASUREMENTS:
      Bone mineral density, biochemical markers of bone remodeling, calciotropic
      hormone levels, biochemically evaluated nutritional and immunologic status, and
      muscle strength were measured every 6 months. RESULTS: Compared with controls,
      patients who received protein supplements had significantly greater increases in
      serum levels of insulin-like growth factor-I (85.6% +/- 14.8% and 34.1% +/- 7.2%
      at 6 months; difference, 51.5 percentage points [95% CI, 18.6 to 84.4 percentage
      points]; P = 0.003) and an attenuation of the decrease in proximal femur bone
      mineral density (-2.29% +/- 0.75% and -4.71% +/- 0.77% at 12 months; difference,
      2.42 percentage points [CI, 0.26 to 4.59 percentage points]; P = 0.029). Seven
      and 13 new vertebral deformities were found among patients who received protein
      supplements and controls, respectively (P > 0.2). Median stay in rehabilitation
      wards was shorter for patients who received protein supplements than for controls
      (33 days [CI, 29 to 56 days] and 54 days [CI, 44 to 62 days]; difference, 21 days
      [CI, 4 to 25 days]; P = 0.018). CONCLUSION: Protein repletion after hip fracture
      was associated with increased serum levels of insulin-like growth factor-I,
      attenuation of proximal femur bone loss, and shorter stay in rehabilitation
      hospitals.

PMID- 9599193
TI  - The effect of antilymphocyte induction therapy on renal allograft survival. A
      meta-analysis of individual patient-level data. Anti-Lymphocyte Antibody
      Induction Therapy Study Group.
AB  - PURPOSE: Randomized, controlled trials have not shown that the perioperative use
      of antilymphocyte antibodies (induction therapy) improves survival of cadaveric
      kidney allografts. This study combined individual patient-level data from
      published trials to examine the effect of induction therapy on allograft
      survival. DATA SOURCES: Randomized, controlled trials identified from MEDLINE.
      STUDY SELECTION: Published trials that compared adult recipients of cadaveric
      renal allografts who did and did not receive antilymphocyte antibodies in the
      perioperative period were selected if individual patient-level data were
      available. DATA EXTRACTION AND ANALYSIS: Individual patient-level data were
      collected for each of 628 study patients. Multivariable Cox proportional hazards
      regression was used to estimate the effect of induction therapy on allograft
      survival. RESULTS: The adjusted rate ratio for allograft failure with induction
      therapy compared with conventional therapy was 0.62 (95% CI, 0.43 to 0.90) (P =
      0.012) over 2 years and 0.82 (CI, 0.62 to 1.09) (P = 0.17) over 5 years. The
      effect of induction therapy on allograft survival diminished over time; no
      benefit overall was seen after 2 years after transplantation (rate ratio, 1.13
      [CI, 0.72 to 1.78]) (P > 0.2). Greater HLA-DR mismatch, delayed allograft
      function, diabetes mellitus in the recipient, African-American ethnicity of the
      recipient, and presensitization (panel-reactive antibody levels > or = 20%) were
      significantly associated with allograft failure at 5 years. Among high-risk
      patients, only those who were presensitized benefited from induction therapy at 2
      years (rate ratio, 0.12 [CI, 0.03 to 0.44]) (P = 0.001). Results were similar at
      5 years. CONCLUSIONS: Using individual-level data, this study showed a benefit of
      induction therapy at 2 years, particularly among presensitized patients. Although
      the benefit of this therapy subsequently waned, presensitized patients continued
      to have benefit at 5 years.

PMID- 9599194
TI  - Acute HIV syndrome after discontinuation of antiretroviral therapy in a patient
      treated before seroconversion.

PMID- 9599195
TI  - Warfarin use and risk for osteoporosis in elderly women. Study of Osteoporotic
      Fractures Research Group.
AB  - BACKGROUND: Vitamin K deficiency may be associated with osteoporosis. OBJECTIVE:
      To assess the effects of warfarin on bone. DESIGN: Prospective observational
      study. SETTING: Four centers in the United States. PARTICIPANTS: 6201 elderly,
      postmenopausal women. MEASUREMENTS: Self-reported warfarin use, bone mineral
      density at the hip and the heel, hip bone loss over 2 years, and fractures during
      3.5 years of follow-up. Analyses were adjusted for baseline differences, age,
      weight, and estrogen use. RESULTS: Compared with warfarin nonusers (n = 6052),
      warfarin users (n = 149) more frequently had poor health, involuntary weight
      loss, nonthiazide diuretic use, and frailty but had similar bone mineral density
      at the hip (difference, 1.6% [95% CI, -0.7% to 4.1%]) and heel (difference, 2.1%
      [CI, -1.6% to 5.6%]). Users and nonusers had similar rates of bone loss (1.1% and
      0.8%; P = 0.18) and fractures (relative hazard, 1.0 [CI, 0.60 to 1.71).
      CONCLUSION: In this population, warfarin use did not decrease bone mineral
      density or increase fracture rates.

PMID- 9599196
TI  - Physicians as leaders in the improvement of health care systems.
AB  - Physicians are often asked to assume leadership roles in their practices,
      hospitals, and academic departments. These positions can be excellent leverage
      points for improvement of health care quality. To make optimal use of these
      opportunities, physicians must learn how to lead. This paper is intended to be a
      primer for physicians who are asked to lead and want to learn how to lead well. A
      body of knowledge that physician-leaders should acquire is described, and case
      examples are used to address such topics as the nature of leadership, the
      relation between leadership and management, and ways in which physicians might
      approach a new leadership assignment. Guidelines for physicians who must play the
      role of followers are offered, and challenges that physicians who lead other
      physicians may face are described.

PMID- 9599197
TI  - Electron-beam computed tomography, coronary artery calcium, and evaluation of
      patients with coronary artery disease.
AB  - PURPOSE: To briefly review the role of calcium in the pathophysiology of
      atherosclerosis and to comprehensively review and analyze studies of coronary
      artery calcium detected by electron-beam computed tomography (CT). DATA SOURCES:
      The English-language literature located through MEDLINE and Current Contents.
      STUDY SELECTION: All studies of electron-beam CT in symptomatic and asymptomatic
      patients with and without known coronary artery disease were selected. DATA
      EXTRACTION: Significant findings on the association of cardiac risk factors and
      angiographically evident coronary artery disease with coronary artery calcium
      detected on electron-beam CT were compared. Prospective data on clinical outcomes
      in patients with coronary artery calcium were assessed. DATA SYNTHESIS: Coronary
      artery calcium is common in patients with known coronary artery disease or risk
      factors for coronary artery disease, and it becomes more common with increasing
      age. Coronary artery calcium detected by electron-beam CT is a sensitive but not
      a specific indicator of angiographically evident atherosclerosis; sensitivity is
      increased and specificity is decreased for angiographically significant disease.
      Test characteristics can be adjusted to improve specificity at the cost of
      sensitivity. Very limited data suggest that patients with coronary artery calcium
      are more likely to have cardiac events. CONCLUSIONS: Electron-beam CT is a
      promising new tool for the evaluation of coronary artery disease because patients
      who have coronary artery calcium are likely to have angiographically evident
      atherosclerosis. However, too few data currently exist to support the broad use
      of this tool in clinical decision making during the evaluation of patients with
      known or suspected coronary artery disease.

PMID- 9599198
TI  - The pathogenesis of mucosal inflammation in murine models of inflammatory bowel
      disease and Crohn disease.
AB  - In recent years, it has become apparent that overproduction of the Th1 cytokines
      interleukin-12 and interferon-gamma is the probable driving force behind murine
      models of intestinal inflammation resembling Crohn disease and intestinal
      inflammation in humans with Crohn disease. In addition, studies of murine models
      strongly suggest that this overproduction is associated with inadequate secretion
      of the counter-regulatory and anti-inflammatory cytokine transforming growth
      factor-beta. Thus, mucosal inflammation in models (and possibly in humans) may
      result from an imbalance between normally occurring positive (immunogenic or
      inflammatory) responses and negative (tolerogenic or anti-inflammatory) mucosal
      immune responses. These new findings and the hypotheses that arise from them are
      being used to construct new approaches to the treatment of Crohn disease that are
      based on the administration of anti-inflammatory cytokines and anti-cytokine
      antibodies.

PMID- 9599199
TI  - Internal medicine in the current health care environment: a need for
      reaffirmation.
AB  - Managed care has substantially changed the environment of health care delivery
      for general internists and internist-subspecialists. In the current system, one
      may wonder whether detailed and thoughtful workups still have a role when the
      direction of medical practice increasingly prizes a high volume of brief
      encounters. However, the very forces that drive managed care make the role of
      internist in the care of adults even more central. The internist's unique
      training and clinical approach should lead to both medically effective and cost
      effective health care for adults. This type of health care will be increasingly
      important as the U.S. population ages and an increasing number of Americans have
      chronic, multisystem disease. Over the past century, internal medicine has
      evolved from a consultative model to a discipline that encompasses total adult
      care, from prevention to diagnosis and treatment of acute and chronic illness and
      from outpatient care in the office to inpatient care in the intensive care unit.
      However, the leadership role of internists in the medical care of adults is now
      being threatened by family medicine and by fragmentation within internal medicine
      itself. Managed care organizations and the general public must be shown why
      internists are better able than family physicians to meet the health care needs
      of adults. Furthermore, as the marketplace becomes more competitive, the issue of
      when care given by a subspecialist is superior to that given by an internist has
      become more prominent. The rapidly developing "hospitalist" movement also
      threatens the traditional role of the internist as the caregiver for adults in
      health and disease. Given the historic flexibility of internal medicine and the
      assumption that appropriate roles can be defined for family physicians,
      subspecialists, and hospitalists, internists will continue to play a central role
      in providing the best care for adults in the new world of health care delivery.

PMID- 9599201
TI  - Variation in the delivery of health care: the stakes are high.

PMID- 9599200
TI  - Antilymphocyte antibodies, renal transplantation, and meta-analysis.

PMID- 9599202
TI  - Doing everything.

PMID- 9599204
TI  - Guidelines for glycemic control in type 2 diabetes.

PMID- 9599203
TI  - Update in endocrinology.

PMID- 9599205
TI  - Cost-effectiveness of echocardiography after stroke.

PMID- 9599206
TI  - Cost-effectiveness of echocardiography after stroke.

PMID- 9599207
TI  - Intracoronary stenting for postpartum coronary artery dissection.

PMID- 9599208
TI  - Erythrocyte sedimentation rate and C-reactive protein in the diagnosis of
      polymyalgia rheumatica.

PMID- 9599209
TI  - Cardiac arrest and myocardial infarction immediately after sumatriptan injection.

PMID- 9599210
TI  - Large-database research: complement to randomized trials?

PMID- 9599211
TI  - The language of case histories.

PMID- 9599212
TI  - The language of case histories.

PMID- 9599213
TI  - The language of case histories.

PMID- 9599214
TI  - The language of case histories.

PMID- 9599215
TI  - The language of case histories.

PMID- 9599216
TI  - The language of case histories.

PMID- 9599217
TI  - The language of case histories.

PMID- 9599218
TI  - Medical libraries today.

PMID- 9599219
TI  - Progress treating childhood diseases creates challenges in adult care.

PMID- 9599220
TI  - Limitations of solvent fractionation methods for urinary and faecal porphyrins.

PMID- 9599221
TI  - The beginnings of the New England Surgical Society.

PMID- 9599223
TI  - Of mice and men (and rats): caveats in defining specific roles of GTP in the
      pancreatic islet.

PMID- 9599224
TI  - Potent antagonists of the SH2 domain of Grb2: optimization of the X+1 position of
      3-amino-Z-Tyr(PO3H2)-X+1-Asn-NH2.

PMID- 9599225
TI  - Design and synthesis of cyclic inhibitors of matrix metalloproteinases and TNF
      alpha production.

PMID- 9599226
TI  - Macrocyclic amino carboxylates as selective MMP-8 inhibitors.

PMID- 9599222
TI  - Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a
      wide variety of precursor proteins.
AB  - Limited endoproteolysis of inactive precursor proteins at sites marked by paired
      or multiple basic amino acids is a widespread process by which biologically
      active peptides and proteins are produced within the secretory pathway in
      eukaryotic cells. The identification of a novel family of endoproteases
      homologous with bacterial subtilisins and yeast Kex2p has accelerated progress in
      understanding the complex mechanisms underlying the production of the bioactive
      materials. Seven distinct proprotein convertases of this family (furin, PC2,
      PC1/PC3, PC4, PACE4, PC5/PC6, LPC/PC7/PC8/SPC7) have been identified in mammalian
      species, some having isoforms generated via alternative splicing. The family has
      been shown to be responsible for conversion of precursors of peptide hormones,
      neuropeptides, and many other proteins into their biologically active forms.
      Furin, the first proprotein convertase to be identified, has been most
      extensively studied. It has been shown to be expressed in all tissues and cell
      lines examined and to be mainly localized in the trans-Golgi network, although
      some proportion of the furin molecules cycle between this compartment and the
      cell surface. This endoprotease is capable of cleaving precursors of a wide
      variety of proteins, including growth factors, serum proteins, including
      proteases of the blood-clotting and complement systems, matrix
      metalloproteinases, receptors, viral-envelope glycoproteins and bacterial
      exotoxins, typically at sites marked by the consensus Arg-Xaa-(Lys/Arg)-Arg
      sequence. The present review covers the structure and function of mammalian
      subtilisin/Kex2p-like proprotein convertases, focusing on furin (EC 3.4.21.85).

PMID- 9599227
TI  - Development of a binding model to protein tyrosine kinases for substituted
      pyrido[2,3-d]pyrimidine inhibitors.
AB  - Previously, our laboratories have reported on a new class of highly potent
      tyrosine kinase inhibitors based on the pyrido[2, 3-d]pyrimidine core template.
      To understand the structural basis for the potency and specificity, a model for
      the binding mode of this class of inhibitors to the tyrosine kinase domains of c
      Src, PDGFr, FGFr, and EGFr tyrosine kinases was developed from structural
      information (principally utilizing the catalytic domain of c-AMP-dependent
      protein kinase as template) and structure-activity relationship (SAR)
      information. In the resulting docking mode, the pyrido[2,3-d]pyrimidine template
      shows a hydrogen-bonding pattern identical to that of olomoucine. The 6-aryl
      substituent of the heterocycle is located deep in the binding cleft in a pocket
      not used by ATP, which helps to confer high-affinity binding as well as
      specificity. The 2-anilino and 2-(dialkylamino)alkylamino substituents as well as
      the 7-urea substituent of inhibitors within this class are located at the
      entrance of the binding cleft and make contact with residues in the hinge region
      between the two kinase lobes. This allows considerable variability and bulk
      tolerance for C-2 and N-7 substituents. The models presented here are consistent
      with the SAR seen for the inhibition of a number of isolated enzymes and provide
      a structural basis to explain their specificity. They have been used successfully
      to design new highly potent protein kinase inhibitors.

PMID- 9599228
TI  - 32-Ascomycinyloxyacetic acid derived immunosuppressants. Independence of
      immunophilin binding and immunosuppressive potency.
AB  - The potent immunosuppressant ascomycin (1b) was selectively alkylated at the C-32
      carbinol, thus providing esters and amides of 32-ascomycinyloxyacetic acid (4,
      AOAA). These compounds present structural variation at the FKBP/calcineurin
      interface. While the native carboxylic acid 4 shows no activity in vitro, esters
      and simple amides of 4 exhibit potent immunosuppression in the human MLR assay.
      Moreover, amides show inhibitory activity in the rat popliteal lymph node
      hyperplasia assay. Surprisingly, FKBP binding was weakened by several orders of
      magnitude when secondary hydrophobic aryl amides of 4 were tested, while
      maintaining potent immunosuppressive efficacy in vitro.

PMID- 9599229
TI  - Structure-activity relationship of 2-[[(2-pyridyl)methyl]thio]-1H- benzimidazoles
      as anti Helicobacter pylori agents in vitro and evaluation of their in vivo
      efficacy.
AB  - A relationship between the structure of 21 2-[[(2-pyridyl)methyl]thio]-1H
      benzimidazoles (6) and their anti Helicobacter pylori activity expressed as
      minimum bactericidal concentration (MBC) values is described. Observed MBCs
      ranged from 256 to 1 microg/mL. The structure-activity relationship (SAR) showed
      that larger and more lipophilic compounds, especially compounds with such
      substituents in the 4-position of the pyridyl moiety, generally had lower MBC
      values. Four new compounds that were predicted to be potent by the established
      SAR model were synthesized and tested. One such compound, i.e., 2-[[(4
      [(cyclopropylmethyl)oxy]-3-methyl-2-pyridyl)methyl]thio]-1H-be nzimidazole (18),
      was tested for in vivo efficacy in a mouse Helicobacter felismodel (125
      micromol/kg bid given orally for 4 days, n = 4). Unfortunately, antibacterial
      activity could not be clearly demonstrated in this model. Instead a potent acid
      secretion inhibition was observed. This finding was attributed to the methylthio
      compound being oxidized to the corresponding methyl sulfinyl derivative, i.e., a
      proton pump inhibitor, in vivo. Although the antibacterial activity had the
      potential of decreasing H. felis cell counts in vivo the proton pump inhibitory
      effect became dominant and actually promoted H. felis cell growth. Hence, we
      conclude that the antibacterial utility of the 2-[[(2-pyridyl)methyl]thio]-1H
      benzimidazoles (6) as a compound class is compromised by their propensity to
      become proton pump inhibitors upon metabolic oxidation in vivo.

PMID- 9599230
TI  - Hydroxyphthalocyanines as potential photodynamic agents for cancer therapy.
AB  - A series of benzyl-substituted phthalonitriles, substituted at the 3-, 4-, and
      4,5-positions, underwent varied condensations with phthalonitrile to give a
      series of protected (monohydroxy- and polyhydroxyphthalocyaninato)zinc(II)
      derivatives which were readily cleaved to give several hydroxyphthalocyanines
      (ZnPc) (phthalocyanine phenol analogues). Their efficacy as sensitizers for the
      photodynamic therapy (PDT) of cancer was evaluated on the EMT-6 mammary tumor
      cell line. In vitro, the 2-hydroxy ZnPc (32) was the most active, followed by the
      2,3- and 2,9-dihydroxy ZnPc (39 and 45), with the 2,9,16-trihydroxy ZnPc (33)
      exhibiting the least activity. In vivo, the monohydroxy derivative 32 and the 2,3
      dihydroxy derivative 39 were both efficient in inducing tumor necrosis at 1
      micromol kg-1, but complete tumor regression was poor, even at 2 micromol/kg. In
      contrast, the 2,9-dihydroxy isomer 45, at 2 micromol kg-1, induced tumor necrosis
      in all animals treated, with 75% complete regression. These results underline the
      importance of the position of the substituents on the Pc macrocycle to optimize
      tumor response and confirm the PDT potential of the unsymmetrical Pcs bearing
      functional groups on adjacent benzene rings.

PMID- 9599231
TI  - Three-dimensional models of estrogen receptor ligand binding domain complexes,
      based on related crystal structures and mutational and structure-activity
      relationship data.
AB  - On the basis of the recently determined crystal structures of the ligand binding
      domains (LBDs) of the retinoic acid nuclear receptors (NRs), we present a three
      dimensional (3D) molecular model of the human estrogen receptor alpha (hERalpha)
      LBD. A literature search for mutants affecting the binding properties has been
      performed; 45 out of 48 published mutants can be explained satisfactorily on the
      basis of the model. Estradiol has been docked into the binding pocket to probe
      its interactions with the protein. Energy minimizations and molecular dynamics
      calculations were performed for various ligand orientations. To evaluate their
      quality, the different models were scored using known structure-activity
      relationship (SAR) data for selected close estradiol homologues. The two best
      models explain largely the binding affinities of more distantly related ligands.

PMID- 9599232
TI  - Molecular modeling of phenothiazines and related drugs as multidrug resistance
      modifiers: a comparative molecular field analysis study.
AB  - A set of 40 phenothiazines, thioxanthenes, and structurally related drugs with
      multidrug resistance modulating activity in tumor cells in vitro were selected
      from literature data and subjected to three-dimensional quantitative structure
      activity relationship study using comparative molecular field analysis (CoMFA).
      More than 350 CoMFA models were derived and evaluated using steric,
      electrostatic, and hydrophobic fields alone and in combination. Four alignment
      strategies based on selected atom pairs or field fit alignment were compared.
      Several training and test sets were analyzed for both neutral and protonated drug
      forms separately. Each chemical class was trained and tested individually, and
      finally the classes were combined together into integrated models. All models
      obtained were statistically significant and most of them highly predictive. All
      fields contributed to MDR reversing activity, and hydrophobic fields improved the
      correlative and predictive power of the models in all cases. The results point to
      the role of hydrophobicity as a space-directed molecular property to explain
      differences in anti-MDR activity of the drugs studied.

PMID- 9599233
TI  - Synthesis, rotamer orientation, and calcium channel modulation activities of
      alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3- or 6-substituted-2
      pyridyl)-5-pyridinecarboxylates.
AB  - A group of racemic alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-
      or 6-substituted-2-pyridyl)-5-pyridinecarboxylates (13a-q) was prepared using a
      modified Hantzsch reaction that involved the condensation of a 3- or 6
      substituted-2-pyridinecarboxaldehyde (7a-j) with an alkyl or 2-phenethyl 3
      aminocrotonate (11a-d) and nitroacetone (12). Nuclear Overhauser (NOE) studies
      indicated there is a significant rotamer fraction in solution where the pyridyl
      nitrogen is oriented above the 1,4-dihydropyridine ring, irrespective of whether
      a substituent is located at the 3- or 6-position. A potential H-bonding
      interaction between the pyridyl nitrogen free electron pair and the suitably
      positioned 1,4-dihydropyridine NH moiety may stablize this rotamer orientation.
      In vitro calcium channel antagonist and agonist activities were determined using
      guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium
      (GPLA) assays, respectively. Compounds having an i-Pr ester substituent acted as
      dual cardioselective calcium channel agonists (GPLA)/smooth muscle-selective
      calcium channel antagonists (GPILSM), except for the C-4 3-nitro-2-pyridyl
      compound which exhibited an antagonist effect on both GPLA and GPILSM. In
      contrast, the compounds with a phenethyl ester group, which exhibited antagonist
      activity (IC50 = 10(-5)-10(-7) M range) on GPILSM, were devoid of cardiac agonist
      activity on GPLA. Structure-activity relationships showing the effect of a
      substituent (Me, CF3, Cl, NO2, Ph) at the 3- or 6-position of a C-4 2-pyridyl
      moiety and a variety of ester substituents (Me, Et, i-Pr, PhCH2CH2-) upon calcium
      channel modulation are described. Compounds possessing a 3- or 6-substituted-2
      pyridyl moiety, in conjuction with an i-Pr ester substituent, are novel 1,4
      dihydropyridine calcium channel modulators that offer a new drug design approach
      directed to the treatment of congestive heart failure and may also be useful as
      probes to study the structure-function relationships of calcium channels.

PMID- 9599234
TI  - Identification of novel ligands for the gabapentin binding site on the
      alpha2delta subunit of a calcium channel and their evaluation as anticonvulsant
      agents.
AB  - As part of a program to investigate the structure-activity relationships of
      Gabapentin (Neurontin), a number of alkylated analogues were synthesized and
      evaluated in vitro for binding to the Gabapentin binding site located on the
      alpha2delta subunit of a calcium channel. A number of other bridged and
      heterocyclic analogues are also reported along with their in vitro data. Two
      compounds showing higher affinity than Gabapentin were selected for evaluation in
      an animal model of epilepsy. One of these compounds, cis-(1S,3R)-(1-(aminomethyl)
      3-methylcyclohexyl)acetic acid hydrochloride (19), was shown to be effective in
      this model with a profile similar to that of Gabapentin itself.

PMID- 9599235
TI  - Propofol analogues. Synthesis, relationships between structure and affinity at
      GABAA receptor in rat brain, and differential electrophysiological profile at
      recombinant human GABAA receptors.
AB  - A number of propofol (2,6-diisopropylphenol) congeners and derivatives were
      synthesized and their in vitro capability to affect GABAA receptors determined by
      the inhibition of the specific [35S]-tert-butylbicyclophosphorothionate
      ([35S]TBPS) binding to rat whole brain membranes. Introduction of halogen (Cl,
      Br, and I) and benzoyl substituents in the para position of the phenyl group
      resulted in ligands with higher potency at inhibiting [35S]TBPS binding. A
      quantitative structure-affinity relationship (QSAR) study demonstrated that
      affinity is enhanced by increases in lipophilicity of the ligand whereas affinity
      is adversely affected by increases in size of the substituent para to the
      phenolic hydroxyl group. Consistent with the displacement of [35S]TBPS and with
      the activation of GABAA receptors, we demonstrate that ligands displaying high
      affinity (i.e., 2-4, and 8) are able to increase GABA-stimulated chloride
      currents in oocytes expressing human GABAA receptors and to directly activate
      chloride currents in an electrophysiological assay. Among them, compound 4 showed
      a rather peculiar profile in the electrophysiological examination with cloned
      alpha1beta2gamma2 GABAA receptors. Indeed, compared to propofol, it displayed a
      much greater efficacy at potentiating GABA-elicited chloride currents, but a much
      lower efficacy at producing a direct activation of the chloride channel in the
      absence of GABA. This behavior may give to compound 4 pharmacological properties
      that are more similar to anxiolytic and anticonvulsant drugs than to those of
      general anesthetics.

PMID- 9599236
TI  - New azole antifungals. 2. Synthesis and antifungal activity of
      heterocyclecarboxamide derivatives of 3-amino-2-aryl-1-azolyl-2-butanol.
AB  - A series of 92 azole antifungals containing an amido alcohol unit was
      synthesized. The nature and substitution of the amide portion was systematically
      modified in search of improved antifungal activity, especially against
      filamentous fungi. The compounds were tested in vitro against a variety of
      clinically important pathogens and in vivo (po) in a murine candidosis model.
      Thiazole and thiophene carboxamides carrying both a substituted phenyl ring and a
      small alkyl group were best suited for activity against filamentous fungi. In a
      subset of these compounds, the amide portion was conformationally locked by means
      of a pyrimidone ring and it was proven that only an orthogonal orientation of the
      phenyl ring yields bioactive products. A tendency to display long plasma
      elimination half-lives was observed in both series. Two compounds, 74 and 107,
      representative of the open and cyclic amides, respectively, were chosen for
      further studies, based on their excellent activity in in vivo murine models of
      candidosis and aspergillosis. This work describes the SARs found within this
      series. The next paper displays the results obtained in a related series of
      compounds, the quinazolinones.

PMID- 9599237
TI  - New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted
      4(3H)-quinazolinones.
AB  - A series of azole antifungal agents featuring a quinazolinone nucleus have been
      subjected to studies of structure-activity relationships. In general, these
      compounds displayed higher in vitro activities against filamentous fungi and
      shorter half-lives than the structures described in our preceding paper. The most
      potent products in vitro carried a halogen (or an isostere) at the 7-position of
      the quinazolinone ring. Using a murine model of systemic candidosis, oral
      activity was found to be dependent on hydrophobicity, which, in turn, modulated
      the compound's half-life. The 7-Cl derivative, (1R,2R)-7-chloro-3-[2-(2, 4
      difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2, 4-triazol-1-yl)propyl]quinazolin
      4(3H)-one (20, UR-9825), was selected for further testing due to its high in
      vitro activity, low toxicity, good pharmacokinetic profile, and ease of
      obtention. Compound 20 is the (1R,2R) isomer of four possible stereoisomers. The
      other three isomers were also prepared and tested. The enantiomer (1S,2S) and the
      (1R,2S) epimer were inactive, whereas the (1S,2R) epimer retained some activity.
      In vitro 20 was superior to fluconazole, itraconazole, SCH-42427, and TAK-187 and
      roughly similar to voriconazole and ER-30346. In vivo, 20 was only moderately
      active in a mouse model of systemic candidosis when administration was limited to
      the first day. This was attributed to its short half-life in that species (t1/2 =
      1 h po). Protection levels comparable to or higher than those of fluconazole,
      however, were observed in systemic candidosis models in rat and rabbit, where the
      half-life of the compound was found to be 6 and 9 h, respectively. Finally, 20
      showed excellent protection levels in an immunocompromised rat model of
      disseminated aspergillosis. The compound showed low toxicity signs when
      administered to rats at 250 mg/kg qd or at 100 mg/kg bid during 28 days.

PMID- 9599238
TI  - Synthesis and structure-activity relationships of bafilomycin A1 derivatives as
      inhibitors of vacuolar H+-ATPase.
AB  - The macrolide antibiotic bafilomycin A1 is a highly potent and selective
      inhibitor of all the vacuolar ATPases (V-ATPases). With the aim of obtaining
      novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31
      derivatives of bafilomycin A1 were synthesized and tested for their ability to
      inhibit differentially the V-ATPase-driven proton transport in membrane vesicles
      derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG).
      Although none of the new analogues were more potent than the parent compound, the
      obtained data provided a significant amount of information about the structural
      requirements for the inhibitory activity of bafilomycin A1. The different effects
      of a few analogues on the two enzymes could also suggest the possibility of a
      selective modulation of the V-ATPases in different tissues.

PMID- 9599239
TI  - Potent dipeptide inhibitors of the pp60c-src SH2 domain.
AB  - The design, synthesis, and evaluation of dipeptide analogues as ligands for the
      pp60c-src SH2 domain are described. The critical binding interactions between Ac
      Tyr-Glu-N(n-C5H11)2 (2) and the protein are established and form the basis for
      our structure-based drug design efforts. The effects of changes in both the C
      terminal (11-27) and N-terminal (51-69) portions of the dipeptide are explored.
      Analogues with reduced overall charge (92-95) are also investigated. We
      demonstrate the feasibility of pairing structurally diverse subunits in a modest
      dipeptide framework with the goal of increasing the druglike attributes without
      sacrificing binding affinity.

PMID- 9599240
TI  - Synthesis and activity of dipeptides, linked to targeting ligands, as specific NK
      cell enhancers.
AB  - Water soluble analogues of the lipophilic immunostimulant, octadecyl D-alanyl-L
      glutamine, BCH-527, were synthesized and evaluated for the ability to stimulate
      natural killer (NK) cells. One of these compounds in which the octadecyl chain of
      BCH-527 was replaced with a shorter chain alcohol, 6-(D-alanyl-L
      glutaminylamino)hexan-1-ol, 9, displayed an in vitro stimulation of NK cells
      comparable to that of interleukin 2 (IL 2). However, when the hydroxyl of 9 was
      linked to L-fucose to yield 1-beta-[6-(D-alanyl-L-glutaminylamino)hex-1-yl]-L-
      fucopyranose (BCH-2537, 1), the observed stimulation of NK cells was greater than
      that observed with IL 2. Further evaluation of these compounds revealed that the
      improved in vitro activity of BCH-2537 was more pronounced in vivo. That is,
      while both compounds significantly increased splenic NK cells, only BCH-2537
      significantly increased the activity of these cells in vivo. In terms of a
      structure-activity relationship, NK cell activity was sensitive to minor
      structural modifications. It was influenced by conservative substitutions within
      the dipeptide, the length of the hydrocarbon chain, and the functionality at the
      end of the chain. No other compound enhanced NK cell activity to the extent
      exhibited by BCH-2537, although a few were equipotent to 9.

PMID- 9599241
TI  - Isoxazolidine-3,5-dione and noncyclic 1,3-dicarbonyl compounds as hypoglycemic
      agents.
AB  - Isoxazolidine-3,5-dione 2 (JTT-501), one of the cyclic malonic acid derivatives,
      was found to decrease blood glucose at an oral dose of 38 mg/kg/day in KKAy mice
      and is currently undergoing evaluation in phase II clinical trials. Further
      studies on a series of malonic acids and related compounds showed that the 1,3
      dicarbonyl structure was important for insulin-sensitizing activity. Dimethyl
      malonate 10, which was selected as a successor for 2, was the optimum compound in
      a series of 1,3-dicarbonyl compounds and was more potent than the corresponding
      thiazolidine-2,4-dione 1.

PMID- 9599242
TI  - (R)-(+)-2-[[[3-(Morpholinomethyl)-2H-chromen-8-yl]oxy]methyl] morpholine
      methanesulfonate: a new selective rat 5-hydroxytryptamine1B receptor antagonist.
AB  - In the search for new 5-hydroxytryptamine (5-HT) receptor antagonists it was
      found that the compound (R)-(+)-2-[[[3-(morpholinomethyl)-2H-chromen-8-yl]oxy]
      methyl] morpholine methanesulfonate, (R)-25, is a selective rat 5
      hydroxytryptamine1B (r5-HT1B) receptor antagonist. The binding profile showed a
      13-fold preference for r5-HT1B (Ki = 47 +/- 5 nM; n = 3) vs bovine 5-HT1B (Ki =
      630 nM; n = 1) receptors. The compound had very low affinity for other
      monoaminergic receptors examined. The r5-HT1B receptor antagonism was
      demonstrated by the potentiation of the K+-stimulated release of [3H]-5-HT from
      superfused rat brain slices in vitro, an effect that was antagonized by addition
      of 5-HT to the superfusion fluid. (R)-25 at 20 mg/kg sc enhanced the 5-HT
      turnover in four rat brain regions (hypothalamus, hippocampus, striatum, and
      frontal cortex) with about 40% measured as the 5-HTP accumulation after
      decarboxylase inhibition with 3-hydroxybenzylhydrazine. At 3 mg/kg sc (R)-25
      produced a significant increase in the number of wet dog shakes in rats, a 5
      HT2A/5-HT2C response that was abolished by depletion of 5-HT after pretreatment
      with the tryptophan hydroxylase inhibitor p-chlorophenylalanine. These
      observations show that (R)-25, by inhibiting terminal r5-HT1B autoreceptors,
      increases the 5-HT turnover and the synaptic concentration of 5-HT.

PMID- 9599243
TI  - Synthesis and structure-activity relationships of potent and orally active 5-HT4
      receptor antagonists: indazole and benzimidazolone derivatives.
AB  - A series of indole-3-carboxamides, indazole-3-carboxamides, and benzimidazolone-3
      carboxamides was synthesized and evaluated for antagonist affinity at the 5-HT4
      receptor in the rat esophagus. The endo-3-tropanamine derivatives in the indazole
      and benzimidazolone series possessed greater 5-HT4 receptor affinity than the
      corresponding indole analogues. 5-HT4 receptor antagonist affinity was further
      increased by alkylation at N-1 of the aromatic heterocycle. In a series of 1
      isopropylindazole-3-carboxamides, replacement of the bicyclic tropane ring system
      with the monocyclic piperidine ring system or an acyclic aminoalkylene chain led
      to potent 5-HT4 receptor antagonists. In particular, those systems in which the
      basic amine was substituted with groups capable of forming hydrogen bonds showed
      increased 5-HT4 receptor antagonist activity. While some of these compounds
      displayed high affinity for other neurotransmitter receptors (in particular, 5
      HT3, alpha1, and 5-HT2A receptors), as the conformational flexibility of the
      amine moiety increased, the selectivity for the 5-HT4 receptor also increased.
      From this series of compounds, we identified LY353433 (1-(1-methylethyl)-N-[2-[4
      [(tricyclo[3.3.1.1(3, 7)]dec-1-ylcarbonyl)amino]-1-piperidinyl]ethyl]-1H-indazole
      3- carboxamide) as a potent and selective 5-HT4 receptor antagonist with
      clinically suitable pharmacodynamics.

PMID- 9599244
TI  - Antitumor agents. 185. Synthesis and biological evaluation of
      tridemethylthiocolchicine analogues as novel topoisomerase II inhibitors.
AB  - Several 1,2,3-tridemethyldeacetylthiocolchicine derivatives have been synthesized
      and evaluated for cytotoxic activity against various human tumor cell lines and
      for their inhibitory effects on DNA topoisomerases in vitro. Exhaustive
      demethylation of thiocolchicine analogues completely changes their biological
      profiles. Instead of displaying antitubulin activity, most target compounds
      inhibited topoisomerase II activity. Only compounds with a larger side chain,
      such as 15a, 23a, and 24a, did not interfere with topoisomerase II enzymatic
      functions. The cytotoxicity of target compounds was reduced by 3 orders of
      magnitude compared to that of colchicine in most cell lines. The hydrophilicity
      of phenolic compounds might prevent drug passage through the cell plasma membrane
      and, thus, be responsible for the relatively weak cytotoxicity. To test this
      hypothesis, 27-30 were prepared from 16a by protecting all hydroxy groups with
      esters with an aim to facilitate drug transportation. In vitro cytotoxicity
      assays indicated that 27 was more potent than its parent compound in all tested
      tumor cell lines and showed tissue selective cytotoxicity with a significant
      inhibitory effect against KB cells (IC50 = 2.7 microg/mL). Therefore, we propose
      that 27 acts as a prodrug, liberating 16a to exert its antitopoisomerase activity
      and, finally, to cause cell death.

PMID- 9599245
TI  - Chemistry and pharmacology of the piperidine-based analogues of cocaine.
      Identification of potent DAT inhibitors lacking the tropane skeleton.
AB  - To discover agents that might be useful in the treatment of cocaine abuse, we
      have chosen to re-explore a class of molecules that was first reported by Clarke
      et al. in 1973 and that was and shown to lack locomotor stimulatory activity in
      mice. These compounds are piperidine-3-carboxylic acid esters bearing a 4
      chlorophenyl group in position 4, and as such, these structures may be viewed as
      truncated versions of the WIN series compounds, i.e., they lack the two-carbon
      bridge of the tropanes. All members of this class were synthesized starting from
      arecoline hydrobromide and obtained in optically pure form through resolution
      methods using either (+)- or (-)-dibenzoyltartaric acid. Interestingly, we have
      found that these piperidines do, in fact, exhibit substantial affinity in both
      WIN 35, 428 binding at the dopamine transporter and in the inhibition of
      [3H]dopamine uptake. Of all of the compounds synthesized, the 3-n-propyl
      derivative (-)-9 was found to be the most potent with a binding affinity of 3 nM.
      This simple piperidine is thus 33-fold more potent than cocaine in binding
      affinity and 29-fold more potent in its inhibition of dopamine uptake. Although
      no efforts have presently been made to "optimize" binding affinity at the DAT,
      the substantive activity found for the n-propyl derivative (-)-9 is remarkable;
      the compound is only about 10-fold less active than the best of the high-affinity
      tropanes of the WIN series. As a further point of interest, it was found that the
      cis-disubstituted piperidine (-)-3 is only about 2-fold more potent than its
      trans isomer (+)-11. This result stands in sharp contrast to the data reported
      for the tropane series, for the epimerization of the substituent at C-2 from beta
      to alpha has been reported to result in a lowering of activity by 30-200-fold.
      This smaller spread in binding affinities for the piperidines may reflect the
      smaller size of these molecules relative to the tropanes, which allows both the
      cis and the trans isomers to adjust themselves to the binding site on the DAT.
      Our present demonstration that these piperidine structures do, in fact, possess
      significant DAT activity, taken together with their reported lack of locomotor
      activity, provides a compelling argument for exploring this class of molecules
      further in animal behavioral experiments. The present work thus broadens the
      scope of structures that may be considered as lead structures in the search for
      cocaine abuse medications.

PMID- 9599246
TI  - (+/-)-trans-2-[3-methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N-
      hydroxyureidyl)methylphenyl]-5-(3,4, 5-trimethoxyphenyl)tetrahydrofuran (CMI
      392), a potent dual 5-lipoxygenase inhibitor and platelet-activating factor
      receptor antagonist.
AB  - By incorporating an N-hydroxyurea functionality onto diaryltetrahydrofurans, a
      novel series of compounds was investigated as dual 5-lipoxygenese (5-LO)
      inhibitor and platelet-activating factor (PAF) receptor antagonist. These dual
      functional compounds were evaluated in vitro for 5-LO inhibition in RBL cell
      extracts and human whole blood, and PAF receptor antagonism in a receptor binding
      assay. PAF-induced hemoconcentration and arachidonic acid- and TPA-induced ear
      edema in mice were used to determine in vivo activities. The structure-activity
      relationship analysis to define a preclinical lead is presented. (+/-)-trans-2-[3
      methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl- N-h ydroxyureidyl)methylphenyl]
      5-(3,4, 5-trimethoxyphenyl)tetrahydrofuran (40, CMI-392) was selected for further
      study. In the arachidonic acid-induced mouse ear edema model, 40 was more potent
      than either zileuton (a 5-LO inhibitor) or BN 50739 (a PAF receptor antagonist),
      and it demonstrated the same inhibitory effect as a physical combination of the
      latter two agents. These results suggest that a single compound which both
      inhibits leukotriene synthesis and blocks PAF receptor binding may provide
      therapeutic advantages over single-acting agents. The clinical development of
      compound 40 is in progress.

PMID- 9599247
TI  - Investigation of the N-substituent conformation governing potency and mu receptor
      subtype-selectivity in (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine opioid
      antagonists.
AB  - A study of the binding site requirements associated with the N-substituent of (+)
      (3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) derivatives was undertaken
      using a set of rigid vs flexible N-substituents. The study showed that compounds
      7-9 bearing the trans-cinnamyl N-substituent most closely reproduced the potency
      at the opioid receptor of the flexible N-propylphenyl or N-propylcyclohexyl
      analogues previously reported. Neither the N-substituted cis-cinnamyl nor the cis
      phenylcyclopropylmethyl compounds 10 and 11, respectively, showed high affinity
      for the opioid receptor. However, the N-trans-phenylcyclopropylmethyl compound 12
      closely approximated the affinity of compounds 7-9. Additionally, we found that
      free rotation of the phenyl ring is necessary for high affinity binding and mu
      receptor subtype selectivity as the planar N-substituted thianaphthylmethyl and
      benzofuranylmethyl compounds 13 and 14 had significantly lower binding
      affinities. Altogether, these findings suggest that the high binding affinity,
      selectivity, and antagonist potency of N-propylphenyl or N-propylcyclohexyl
      analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) are achieved
      via a conformation wherein the connecting chain of the N-substituents is extended
      away from piperidine nitrogen with the appended ring system rotated out-of-plane
      relative to the connecting chain atoms. This conformation is quite similar to
      that observed in the solid state for 5, as determined by single crystal X-ray
      analysis. Additionally, it was found that, unlike naltrexone, N-substituents
      bearing secondary carbons attached directly to the piperidine nitrogen of 4
      suffer dramatic losses of potency vs analogues not substituted in this manner.
      Using a functional assay which measured stimulation or inhibition of [35S]GTP
      gamma-S binding, we show that the trans-cinnamyl analogues of (+)-(3R, 4R)
      dimethyl-4-(3-hydroxyphenyl)piperidine (4) retain opioid pure antagonist activity
      and possess picomolar antagonist potency at the mu receptor.

PMID- 9599248
TI  - Submicro inverse-detection gradient NMR: A powerful new way of conducting
      structure elucidation studies with <0.05 &mgr;mol samples 
AB  - Quantities of material required for structural analysis were reduced
      substantially following the introduction of 3 mm microinverse and microdual NMR
      probes in 1992. We now report the first very low-level results obtainable with a
      new 1.7 mm submicro-inverse-detection gradient or SMIDG NMR probe. Using this
      technology at 600 MHz, it was possible to fully characterize an 8% impurity
      contained in a 0. 55 &mgr;mol sample of cryptolepine (1) that had been standing
      in excess of 2 years since its initial isolation. The impurity was unequivocally
      identified as cryptolepinone (2) through the concerted interpretation of GHSQC,
      GHMBC, homonuclear TOCSY, and ROESY spectra in conjunction with APCI LC/MS and
      CID data acquired from a portion of the serial dilution solution used to prepare
      the NMR sample. Submicro-inverse-detection gradient probes offer the prospect of
      reducing still further the quantities of sample required for full
      characterization under favorable circumstances, making rare and potentially novel
      natural products amenable to structural determination. SMIDG NMR technology is
      equally applicable to a range of small samples requiring characterization such as
      isolated impurities from drug substances, isolates from drug degradation studies,
      and secondary metabolites.

PMID- 9599249
TI  - Guaianolides from tanacetum argenteum subsp. canum var. canum 
AB  - The aerial parts of Tanacetum argenteum subsp. canum var. canum (Compositae)
      afforded six guaianolides, five of them (2-6) being new: flabellin (1),
      epoxyflabellin (2), Delta3(4)-15-oxo-flabellin (3), Delta3(4)-15
      hydroxydihydroflabellin (4), 11alpha-dihydroflabellin (5), and 11beta
      dihydroflabellin (6). The structures of the compounds were elucidated by spectral
      methods including NMR (1H NMR, COSY, APT, HETCOR, NOE) and X-ray diffraction, as
      well as by some chemical reactions.

PMID- 9599250
TI  - Antiviral phenylpropanoid glycosides from the medicinal plant Markhamia lutea.
AB  - Three new phenylpropanoid glycosides, named luteoside A (3), luteoside B (4), and
      luteoside C (5), were isolated together with the known compounds verbascoside (1)
      and isoverbascoside (2) from the roots of the medicinal plant Markhamia lutea.
      The structures of the new compounds were determined to be 1-O-(3, 4
      dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)
      4-O- caffeo yl-6-acetyl-beta-d-glucopyranoside, 1-O-(3,4-dihydroxyphenyl)ethyl
      beta-d-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- caffeo yl-beta-d
      glucopyranoside, and 1-O-(3,4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)
      alpha-l-rhamnopyranosyl(1-->3)-6-O- ferulo yl-beta-d-glucopyranoside,
      respectively, on the basis of chemical and spectroscopic data. All five
      phenylpropanoid glycosides exhibited potent in vitro activity against respiratory
      syncytial virus.

PMID- 9599252
TI  - cis-monotetrahydrofuran acetogenins from the roots of annona muricata1 
AB  - Phytochemical investigation of roots of Annona muricata led to the identification
      of seven mono-tetrahydrofuran (mono-THF) acetogenins. Six new acetogenins having
      the unusual cis-configuration of the THF ring, cis-solamin (1), cis-panatellin
      (2), cis-uvariamicin IV (3), cis-uvariamicin I (4), cis-reticulatacin (5), and
      cis-reticulatacin-10-one (6) were identified, in addition to a known compound,
      solamin.

PMID- 9599251
TI  - Petrosaspongiolides M-R: new potent and selective phospholipase A2 inhibitors
      from the New Caledonian marine sponge Petrosaspongia nigra.
AB  - Five new bioactive sesterterpenes (1-5) have been isolated from the New
      Caledonian marine sponge Petrosaspongia nigra Bergquist and named
      petrosaspongiolides M-R. Their chemical structures were determined from 1D and 2D
      NMR studies and MS data. All compounds inhibited different preparations of
      phospholipase A2 (PLA2) by irreversibly blocking these enzymes (particularly
      human synovial and bee venom, see Table 3), with IC50 values in the micromolar
      range. Interestingly, these compounds displayed a much lower activity (or no
      activity at all) toward porcine pancreas and Naja naja venom PLA2 enzymes. The
      most potent compound, 1 (IC50 1.6 and 0.6 microM for human synovial and bee venom
      PLA2 enzymes, respectively), was slightly more active than manoalide (6) (IC50
      3.9 and 7.5 microM) under our experimental conditions. Compound 3 is more
      selective, inhibiting human synovial PLA2 to a greater extent than bee venom
      PLA2.

PMID- 9599253
TI  - Purpurediolin and purpurenin, two new cytotoxic adjacent bis-tetrahydrofuran
      annonaceous acetogenins from the seeds of Annona purpurea.
AB  - Two novel cytotoxic acetogenins, purpurediolin (1) and purpurenin (2), were
      isolated from the seeds of Annona purpurea. Their structures were elucidated by a
      combination of chemical and spectral methods including MS and NMR measurements.
      In addition, six known acetogenins were obtained, namely, bullatacin, squamocin
      (annonin I), motrilin (squamocin C), annoglaucin, xylomatenin, and annonacin A.
      Compounds 1 and 2 exhibited potent cytotoxic activity in vitro against six human
      solid tumor cell lines.

PMID- 9599254
TI  - Evaluation of biological activities of triterpenoid saponins from Maesa
      lanceolata.
AB  - From a bioassay-guided fractionation procedure using Herpes simplex virus type 1
      as the target model, a virucidal saponin mixture (maesasaponin mixture B) was
      isolated from the MeOH extract of leaves of Maesa lanceolata. The maesasaponin
      mixture B consisted of six homologous oleanane-type triterpenoid saponins 1-6,
      identified by 1H, 13C, and 2D NMR spectroscopy and mass spectrometry. The
      maesasaponin mixture B (1-6) showed several biological activities expected for
      saponins. It exhibited a moderate virucidal activity against enveloped viruses.
      The maesasaponin mixture B (1-6) was tested for further properties. The saponin
      mixture was found to be highly hemolytic and molluscicidal: it hemolyzed 50% of
      human erythrocytes (1% suspension) at a concentration estimated at 1.6 microg/mL
      and exerted against Biomphalaria glabrata snails a severe toxic effect with LD95
      and LD50 values of 4.1 and 2.3 ppm, respectively. In addition, the maesasaponin
      mixture B (1-6) showed moderate fungistatic and antimutagenic properties. The
      evaluation of these diverse activities is described.

PMID- 9599256
TI  - Chilocorine C: a new "dimeric" alkaloid from a coccinellid beetle, Chilocorus
      cacti.
AB  - A new hexacyclic alkaloid, chilocorine C (4), has been isolated from Chilocorus
      cacti and characterized on the basis of its IR, UV, MS, and NMR data. Although
      its structure is closely related to that of exochomine (1) (isolated from
      Exochomus quadripustulatus) and to chilocorine A (2) and B (3) (obtained
      previously from C. cacti), the presence of a hydroxymethyl substituent on the
      saturated tricyclic moiety represents an unexpected structural variation on the
      dimeric alkaloid theme.

PMID- 9599255
TI  - Total synthesis and biological activities of (+)- and (-)-boscialin and their 1'
      epimers.
AB  - Natural (-)-boscialin [(-)-1] has recently been described as one of the
      constituents of various medicinal plants. To obtain more material for
      investigations of its biological activities, we carried out the synthesis of (-)
      1 and its isomers. Starting from the chiral building block 2, the key steps of
      the synthesis involved a regioselective reduction and a nucleophilic addition.
      The enantiomer of the natural product, (+)-boscialin [(+)-1], could be obtained
      via acid-catalyzed epimerization of hydroxyketone 4 to (+)-3. Starting the
      synthesis with (-)-3 led to (-)-boscialin [(-)-1] with the natural absolute
      configuration. In addition to (+)- and (-)-boscialin, the corresponding 1'
      epimers (+)- and (-)-epiboscialin were also obtained. In vitro assays with (-)
      boscialin [(-)-1] and its three stereoisomers were carried out to test for
      activity against microbes, parasites, and human fibroblasts. The investigations
      revealed activity against various microbes and against Trypanosoma brucei
      rhodesiense and also revealed cytotoxicity against human cancer cells.

PMID- 9599257
TI  - Novel cytotoxic diterpenes, excavatolides A-E, isolated from the Formosan
      gorgonian Briareum excavatum.
AB  - The chemistry of Briareum excavatum, a Formosan gorgonian coral, was
      investigated. This study has led to the isolation of five novel marine natural
      products, excavatolides A-E (1-5), together with brianolide (6). The structures
      of the above compounds were established by spectral and chemical methods. The
      relative configuration of excavatolide B (2) was further confirmed by a single
      crystal X-ray structure analysis. Cytotoxicity of these compounds toward various
      cancer cell lines also is described.

PMID- 9599258
TI  - Synthesis of (+/-)-cassumunins A and B, new curcuminoid antioxidants having
      protective activity of the living cell against oxidative damage.
AB  - A chemical synthesis of cassumunins A (1) and B (2), natural curcuminoid
      antioxidants, was developed. The synthesis was started from o-vanillin and after
      nine reaction steps resulted in 20% and 26% overall yields of 1 and 2,
      respectively. The synthetic cassumunins showed stronger protective activity than
      curcumin against oxidative cell death induced by hydrogen peroxide in a rat
      thymocyte system.

PMID- 9599259
TI  - Novel and insecticidal isobutylamides from dinosperma erythrococca 
AB  - Through insecticidal bioassay-guided fractionation and isolation, five
      isobutylamides 1-5 were isolated from n-hexane and EtOAc extracts of the aerial
      parts of Dinosperma erythrococca (Rutaceae). The structures of compounds 1-5 were
      established through 1D and 2D NMR. Compounds 1-3 were identified as
      erythrococcamides A-C and represent two novel classes of isobutylamide. Compounds
      4-5 were identified as N-(2-hydroxy-2-methylpropyl)-6-phenyl-2(E), 4(E)
      hexadienamide (4)1,2 and N-(2-methylpropyl)-6-phenyl-2(E), 4(E)-hexadienamide
      (5),1,3 respectively. Compound 1 showed lethal activity against the housefly
      (Musca domestica) (kill EC50 = 20.2 ppm) and the tobacco budworm (Heliothis
      virescens) (kill EC50 = 74.2 ppm). Compound 4 showed lethal activity against H.
      virescens at 500 ppm, while compound 5 showed lethal activity against M.
      domestica at 500 ppm.

PMID- 9599260
TI  - Glacins A and B: two novel bioactive mono-tetrahydrofuran acetogenins from Annona
      glabra.
AB  - Two new bioactive mono-THF Annonaceous acetogenins, glacins A (1) and B (2), have
      been isolated, from the fractionated ethanolic extracts of the leaves of Annona
      glabra, directing the fractionation with the brine shrimp lethality test (BST).
      The structures of 1 and 2 were elucidated on the basis of spectroscopic and
      chemical methods, and the absolute stereochemistries were solved by preparing
      their respective per-Mosher ester derivatives. 1 and 2 showed potent and
      selective in vitro cytotoxicities among several human solid tumor cell lines.

PMID- 9599261
TI  - Nitrogen-containing furanose and pyranose analogues from Hyacinthus orientalis.
AB  - Aqueous methanol extracts from the bulbs of Hyacinthusorientalis were subjected
      to various ion-exchange column chromatographic steps to give 2(R),5(R)
      bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine (DMDP) (1), 2,5-dideoxy-2,5
      imino-dl-glycero-d-manno-heptitol (homoDMDP) (2), 2,5-imino-2,5,6-trideoxy-d
      manno-heptitol (6-deoxy-homoDMDP) (3), 2,5-imino-2,5,6-trideoxy-d-gulo-heptitol
      (4), 1-deoxynojirimycin (5), 1-deoxymannojirimycin (6), alpha-homonojirimycin
      (7), beta-homonojirimycin (8), alpha-homomannojirimycin (9), beta
      homomannojirimycin (10), and 7-O-beta-d-glucopyranosyl-alpha-homonojirimycin (MDL
      25,637) (11). The structures of the new natural products 3 and 4 were determined
      by spectroscopic analysis, including extensive 1D and 2D NMR studies. Compound 2
      was found to be a potent inhibitor of bacterial beta-glucosidase, mammalian beta
      galactosidases, and mammalian trehalases, while 3 was a potent inhibitor of rice
      alpha-glucosidase and rat intestinal maltase. Compound 4 was observed to be a
      good inhibitor of alpha-l-fucosidase.

PMID- 9599263
TI  - Enzymatic synthesis of artemisinin from natural and synthetic precursors.
AB  - To investigate the biosynthetic pathway of artemisinin, an assay system for the
      determination of activity of the enzymes involved in its synthesis has been
      developed. Results from these experiments have shown that HEPES provides a better
      buffer system than Tris-HCl. The enzyme(s) requires Mg2+ and/or Mn2+, and the
      addition of ATP and NADPH+H+ significantly enhances the enzyme activity. A new
      substrate, dihydroarteannuin B, has been synthesized that can easily be
      radiolabeled with high specific activity. It is utilized by the enzyme system and
      is converted to artemisinin with the same efficiency as the natural substrates.
      This can be conveniently used as a precursor for elucidation of the pathway for
      artemisinin biosynthesis.

PMID- 9599262
TI  - Antitumor-promoting naphthoquinones from Catalpa ovata.
AB  - Bioassay-directed fractionation of an extract of the stem-bark of Catalpa ovata
      led to the isolation of three new naphthoquinones: 8-methoxydehydroiso-alpha
      lapachone (1), 9-methoxy-4-oxo-alpha-lapachone (2), and (4S,4aR,10R,10aR)-4, 10
      dihydroxy-2,2-dimethyl-2,3,4,4alpha,10, 10alpha-hexahydrobenzo[g]chromen-5-one
      (3), which is a 1,4-reductive form of 6. The known compounds 3-hydroxydehydroiso
      alpha-lapachone (4), 4,9-dihydroxy-alpha-lapachone (5), 4-hydroxy-alpha-lapachone
      (6), and 9-methoxy-alpha-lapachone (7), and catalpalactone (8) were also
      isolated. Their structures were elucidated by spectral methods. These compounds
      all exhibited significant inhibitory activity against 12-O-tetradecanoylphorbol
      13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation in
      Raji cells.

PMID- 9599264
TI  - Antifungal amide from leaves of Piper hispidum.
AB  - Bioactivity-guided fractionation of a CH2Cl2 extract from leaves of Piper
      hispidum (Piperaceae) yielded a new pyrrolidine amide, N-[7-(3',4'
      methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine 1, in addition to two
      known amides N-[5-(3', 4'-methylenedioxyphenyl)-2(E)-pentadienoyl] pyrrolidine
      and N-[2-(3', 4'-methylenedioxy-6'-methoxyphenyl)-2(Z)-propenoyl]pyrrolidine. The
      structure of compound 1 was elucidated by interpretation of spectral data,
      including ES-MS. Compound 1 showed antifungal activity against Cladosporium
      sphaerospermum.

PMID- 9599265
TI  - Antibacterial activity of lonchocarpol A.
AB  - Lonchocarpol A, a flavanone, demonstrates in vitro inhibitory activity against
      methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus
      faecium. This activity is antagonized by mouse plasma, which may account for its
      lack of in vivo activity. This compound demonstrates no differentiation with
      respect to the inhibition of RNA, DNA, cell wall, and protein synthesis.

PMID- 9599266
TI  - Cytotoxic compounds from the roots of Juglans mandshurica.
AB  - Three new compounds, a diarylheptanone glucoside (1), 4,5, 8-trihydroxy-alpha
      tetralone 5-O-beta-d-[6'-O-(3", 5"-dimethoxy-4"-hydroxybenzoyl)]glucopyranoside
      (2), and 1,4, 8-trihydroxy-3-naphthalenecarboxylic acid 1-O-beta-d
      glucopyranoside methyl ester (3), were isolated from the roots of Juglans
      mandshurica, and their structures were elucidated on the basis of spectroscopic
      studies including 2D-NMR.

PMID- 9599267
TI  - Flexuosol A, a new tetrastilbene from vitis flexuosa 
AB  - A novel tetrastilbenoid, flexuosol A (1), was isolated from the stems of Vitis
      flexuosa together with the known gnetin A, (+)-epsilon-viniferin, vitisin A, and
      hopeaphenol. The structure of 1 was elucidated using spectral methods.

PMID- 9599268
TI  - A new cytosine glycoside from Streptomyces griseochromogenes produced by the use
      in vivo of enzyme inhibitors.
AB  - The identification of new cytosine glycosides and intermediates in the
      biosynthetic pathway of the antifungal antibiotic blasticidin S (1) was
      investigated using in vivo enzyme inhibition. Fermentations of Streptomyces
      griseochromogenes, the organism that produces 1, supplemented with the arginine
      analogue argininic acid or the argininosuccinate synthase inhibitor 2
      methylaspartic acid were found to produce a new metabolite (7).

PMID- 9599269
TI  - Two new cembranoids from croton oblongifolius 
AB  - Two new cembranoids, crotocembraneic acid (1) and neocrotocembraneic acid (2),
      were isolated from the stem bark of Croton oblongifolius. Their structures were
      established on the basis of spectroscopic analysis.

PMID- 9599270
TI  - Isolation, identification, and antioxidant activity of three stilbene glucosides
      newly extracted from vitis vinifera cell cultures 
AB  - Suspension cultures of Vitis vinifera L. (Vitaceae) produce many hydroxylated
      stilbene glucosides found in red wine. From these cells, we isolated and
      characterized glycosylated stilbenes, (Z)-piceatannol (3,5,3',4'
      tetrahydroxystilbene) -3-O-beta-d-glucopyranoside (6) and (E)- and (Z)
      resveratrol (3,5, 4'-trihydroxystilbene)-4'-O-beta-d-glucopyranoside (2 and 7,
      respectively), which have not previously reported to be constituents of Vitis
      vinifera or wine. The ability of these compounds to act as radical scavengers was
      investigated using 1,1 diphenyl-2-picryl-hydrazyl, a stable free radical.
      Antioxidant activities were assessed by their capacity to prevent Cu2+-induced
      lipid peroxidation in human low-density lipoprotein.

PMID- 9599272
TI  - Dragmacidins: new protein phosphatase inhibitors from a southern australian deep
      water marine sponge, spongosorites sp 
AB  - A Spongosorites sp. collected during trawling operations off the southern coast
      of Australia returned the new alkaloid dragmacidin E (3), the structure of which
      was secured by detailed spectroscopic analysis. Dragmacidin E (3), and its co
      metabolite dragmacidin D (1) have been identified as potent inhibitors of serine
      threonine protein phosphatases.

PMID- 9599271
TI  - Pulsatilloside C from the roots of Pulsatilla chinensis.
AB  - A new lupane-type triterpene saponin, pulsatilloside C (1), was isolated from the
      roots of Pulsatilla chinensis. Its structure was established to be 3beta,23
      dihydroxylup-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D
      glucopyranosyl-(1-->6)- beta-D-glucopyranoside.

PMID- 9599273
TI  - Thiomycalolides: new cytotoxic trisoxazole-containing macrolides isolated from a
      marine sponge Mycale sp.
AB  - Two new cytotoxic trisoxazole macrolides, thiomycalolides A (2) and B (3), have
      been isolated from a marine sponge Mycale sp. The structures were determined to
      be glutathione adducts of mycalolides A and B by interpretation of spectral data
      and chemical transformation. Thiomycalolides A and B are highly cytotoxic against
      P388 murine leukemia cells.

PMID- 9599275
TI  - Isolation of 1-carboxymethylnicotinic acid from the marine sponge anthosigmella
      cf. raromicrosclera As a cysteine protease inhibitor1 
AB  - 1-Carboxymethylnicotinic acid (1) has been isolated from a marine sponge
      Anthosigmella cf. raromicrosclera as a cysteine protease inhibitor. The structure
      was elucidated by spectral data and chemical synthesis.

PMID- 9599274
TI  - Cyclotheonamides E2 and E3, new potent serine protease inhibitors from the marine
      sponge of the genus Theonella.
AB  - Two new potent serine protease inhibitors, cyclotheonamides E2 (3) and E3 (4),
      have been isolated from a marine sponge of the genus Theonella. Their structures
      were determined by interpretation of spectral data and chemical degradation
      studies. They are closely related to the previously reported cyclotheonamide E,
      from which they differ in the N-acyl group of the alanyl side chain.
      Cyclotheonamides E, E2, and E3 were more active against thrombin than against
      trypsin.

PMID- 9599276
TI  - Synthesis of (E)-4-oxonon-2-enoic acid, a natural antibiotic produced by
      streptomyces olivaceus 
AB  - (E)-4-Oxonon-2-enoic acid (1), a natural antibiotic produced by Streptomyces
      olivaceus, has been conveniently prepared in three steps starting from furan.

PMID- 9599277
TI  - Identification of 2-methoxyhexadecanoic acid in amphimedon compressa 
AB  - The phospholipid fatty acid composition of Amphimedoncompressa was reinvestigated
      and the 2-methoxyhexadecanoic acid was identified for the first time in nature.
      Structure characterization was accomplished by means of gas chromatography-mass
      spectrometry and total synthesis from commercially available 2
      hydroxyhexadecanoic acid.

PMID- 9599279
TI  - Grenadadiene and grenadamide, cyclopropyl-containing fatty acid metabolites from
      the marine cyanobacterium Lyngbya majuscula.
AB  - Grenadadiene (1), debromogrenadiene (2), and grenadamide (3), three structurally
      unique cyclopropyl-containing metabolites, were isolated from the organic extract
      of a Grenada collection of the marine cyanobacterium Lyngbya majuscula. The
      structures and the relative stereochemistries of these compounds were determined
      using spectroscopic methods. These are the first reported cyclopropyl-containing
      fatty acid derivatives from a Lyngbya sp. Grenadadiene (1) has an interesting
      profile of cytotoxicity in the NCI 60 cell line assay, while grenadamide (2)
      exhibited modest brine shrimp toxicity (LD50 = 5 microg/mL) and cannabinoid
      receptor binding activity (Ki = 4.7 microM).

PMID- 9599280
TI  - A new ceramide with a novel branched-chain fatty acid isolated from the epiphytic
      dinoflagellate coolia monotis 
AB  - From the dinoflagellate Coolia monotis, a new ceramide (1) bearing a 2-hydroxy-15
      methyl-3-octadecenoyl moiety was isolated as a cellular constituent. The
      structure, including the partial absolute configuration, was elucidated as 1 on
      the basis of the 2D NMR of 1, and chiral HPLC and CD examinations with benzoyl
      derivatives of its degradation products. To our knowledge, this is the first
      example, from natural sources, of a C18 fatty acid with a methyl group
      substituted at a C15 carbon.

PMID- 9599278
TI  - Kalkipyrone, a toxic gamma-pyrone from an assemblage of the marine cyanobacteria
      Lyngbya majuscula and Tolypothrix sp.
AB  - Kalkipyrone, a novel alpha-methoxy-beta,beta'-dimethyl-gamma-pyrone possessing an
      alkyl side chain, was isolated from an assemblage of the marine cyanobacteria
      Lyngbyamajuscula and Tolypothrix sp. Its structure, including stereochemistry,
      was determined by NMR, UV, and IR analysis and by GC-MS of the natural product
      and key derivatives. Kalkipyrone is toxic to brine shrimp (LD50 1 microg/mL) and
      gold fish (LD50 2 microg/mL) and is structurally related to the actinopyrones
      that were previously isolated from Streptomyces spp.

PMID- 9599281
TI  - Three new manzamine congeners from amphimedon sponge 
AB  - Three new manzamine congeners (1-3) have been isolated from the Okinawan marine
      sponge Amphimedon sp., and the structures, including relative stereochemistries,
      were elucidated on the basis of spectroscopic data. Absolute configuration at C
      16 of 1 was determined by modified Mosher's method.

PMID- 9599282
TI  - Spongiacidins A-D, new bromopyrrole alkaloids from hymeniacidon sponge 
AB  - Four new bromopyrrole alkaloids, spongiacidins A-D (1-4), have been isolated from
      an Okinawan marine sponge Hymeniacidon sp. and the structures elucidated on the
      basis of spectral data and chemical means.

PMID- 9599283
TI  - Three new metabolites from the marine yeast aureobasidium pullulans 
AB  - Two new diketopiperazines (1 and 2) with a d-cis-4-hydroxyproline residue, and
      orcinotriol (3), a new 1,3-dihydroxyphenol derivative, were isolated from
      cultured broth of the yeast Aureobasidium pullulans, which was isolated from an
      Okinawan marine sponge. The structures of the compounds, including their absolute
      stereochemistries, were determined by spectroscopic data and chemical means.

PMID- 9599284
TI  - Dilemmaones A-C, unusual indole alkaloids from a mixed collection of south
      african sponges 
AB  - Three indole alkaloids, dilemmaones A-C (1-3), were isolated from a mixture of
      sponges that was collected near Cape Town, South Africa. The structures of
      dilemmaones A-C (1-3) were elucidated by interpretation of spectroscopic data.
      The dilemma caused by faulty differentiation of similar specimens in the field is
      discussed in detail.

PMID- 9599285
TI  - Arenarins A-C: new cytotoxic fungal metabolites from the sclerotia of aspergillus
      arenarius 
AB  - Three new terphenyl-type metabolites, arenarins A-C (1-3), have been isolated
      from the sclerotia of Aspergillus arenarius (NRRL 5012). The structures of these
      compounds were elucidated by analysis of 1-D and 2-D NMR data. Arenarins A-C
      exhibited mild activity in feeding assays against the dried-fruit beetle
      Carpophilus hemipterus and cytotoxicity against human tumor cell lines.

PMID- 9599286
TI  - Antioxidant flavonoid glycosides from Daphniphyllum calycinum.
AB  - A novel flavonoid diglycoside, 5,6,7,4'-tetrahydroxyflavonol 3-O-rutinoside (1),
      and a previously known compound, kaempferol 3-O-neohesperidoside (2), were
      isolated from an ethyl acetate extract of Daphniphyllum calycinum leaves that
      showed significant activity in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free
      radical assay. The structure of 1 was elucidated by a combination of
      spectroscopic methods, and compounds 1 and 2 were found to be moderately active
      as antioxidants in the DPPH assay.

PMID- 9599287
TI  - Glandular structure and gene expression. Lessons from the mammary gland.

PMID- 9599288
TI  - Multifunctional lens crystallins and corneal enzymes. More than meets the eye.
AB  - The abundant water-soluble proteins, called crystallins, of the transparent,
      refractive eye lens have been recruited from metabolic enzymes and stress
      protective proteins by a process called "gene sharing." Many crystallins are also
      present at lower concentration in nonocular tissues where they have nonrefractive
      roles. The complex expression pattern of the mouse alpha B-crystallin/small heat
      shock protein gene is developmentally controlled at the transcriptional level by
      a combinatorial use of shared and lens-specific regulatory elements. A number of
      crystallin genes, including that for alpha B-crystallin, are activated by Pax-6,
      a conserved transcription factor for eye evolution. Aldehyde dehydrogenase class
      3 and transketolase are metabolic enzymes comprising extremely high proportions
      of the water-soluble proteins of the cornea and may have structural as well as
      enzymatic roles, reminiscent of lens enzyme-crystallins. Inductive processes
      appear to be important for the corneal-preferred expression of these enzymes. The
      use of the same protein for entirely different functions by a gene-sharing
      mechanism may be a general strategy based on evolutionary tinkering at the level
      of gene regulation.

PMID- 9599289
TI  - The role of stably committed and uncommitted cells in establishing tissues of the
      somite.
AB  - Somites are blocks of embryonic mesoderm tissue that give rise to skeletal
      muscle, cartilage, and other connective tissues. The development of different
      tissues within the somite is influenced by adjacent structures, in particular,
      the neural tube and notochord. Results of experiments performed in vivo and in
      vitro suggest that somites contain populations of cells stably programmed to
      undergo either skeletal myogenesis or chondrogenesis and a population uncommitted
      to either pathway. The fate of the uncommitted cells would depend on a transfer
      of information from the committed cells. Communication between committed and
      uncommitted cells is regulated by cell and tissue interactions that either
      activate or inhibit this process.

PMID- 9599290
TI  - Regulation of the Sex combs reduced gene in Drosophila.
AB  - The Sex combs reduced gene of the Antennapedia complex specifics the identities
      of the anterior thoracic and posterior head segments, including the primordium of
      the larval salivary gland. The Sex combs reduced transcription unit spans over 30
      kb of genomic DNA, with another 40 kb of upstream cis-regulatory sequences. The
      pattern of Sex combs reduced transcription is set in the early embryo by the
      segmentation genes and is then maintained by two competing sets of proteins, the
      Polycomb group and the trithorax group. One of the trithorax group genes required
      for activation, the brahma gene, encodes an evolutionarily conserved DNA
      stimulated ATPase that is part of a large protein complex. This complex
      facilitates the action of sequence-specific, DNA-binding proteins in regulating
      target genes, possibly by altering chromatin structure.

PMID- 9599291
TI  - Integrins and development: how might these receptors regulate differentiation of
      the lens.
AB  - Integrins transduce both internal signals and signals from the matrix. These
      interactions between integrins, their extracellular matrix ligands, and their
      cytoskeletal partners play an important role in the regulation of cellular
      differentiation. We have shown them to be important in lens cell differentiation.
      In the lens capsule there is a compartmentalization of matrix components with
      fibronectin, primarily localized to the anterior capsule, and tenascin in the
      posterior capsule. Integrins are developmentally regulated in the lens. alpha 5
      beta 1 integrin, like fibronectin, is primarily associated with the lens
      epithelial cells, where together they are likely to be important in regulation of
      adhesion and proliferation. alpha 6A beta 1, the integrin laminin receptor, is
      expressed at its highest levels in the equatorial epithelium and the peripheral
      fiber cells, both migratory populations. Because laminin is uniformly distributed
      in the lens capsule, such changes in alpha 6A integrin expression are likely
      critical to the cell's ability to regulate its response to laminin in the matrix.
      The organization of cytoskeletal molecules associated with the integrin
      cytoplasmic face also changes with development. In the epithelial regions of the
      lens, where the initiation of lens cell differentiation occurs, expression of the
      cytoskeletal proteins involved in cell-substrate interactions, talin, alpha
      actinin, and the signaling proteins, are high. In the fiber cell region of the
      lens, where the cells establish stable cell-cell contacts, vinculin predominates
      and becomes highly associated with the cytoskeletal fraction. The role of
      integrins in lens development is not only regulated by changes in the expression
      of different integrin receptors but is also closely correlated with the
      expression and organization of the molecules with which they associate.

PMID- 9599292
TI  - Integrins and matrix molecules in salivary gland cell adhesion, signaling, and
      gene expression.
AB  - Integrins play crucial roles in embryonic and adult cell adhesion, migration,
      morphogenesis, growth, and differentiation in many cell systems, including human
      salivary gland cells. Integrins function by binding through their extracellular
      domain to a specific peptide recognition site in a ligand, and then transmitting
      information to the cytoplasm by way of their cytoplasmic tails. By this
      transmembrane signaling process, integrins can mediate assembly of adhesion sites
      and organization of the actin-containing cytoskeleton by forming supermolecular
      complexes of cytoskeletal and signaling molecules. The specific steps in the
      assembly of these complexes as well as novel mechanisms for synergy between
      integrin and growth factor signaling pathways are still being determined.
      integrin-mediated interactions also have major effects on gene expression. For
      example, integrin-mediated adhesion to fibronectin by the HSG salivary gland cell
      line significantly alters the pattern of proteins synthesized and genes
      expressed. In fact, at least five transcription factors are activated, and over
      30 genes (many of them novel) are found to be induced by such integrin-mediated
      interactions by salivary gland cells. The roles of integrins, in collaborative
      interactions with growth factors and signaling pathways, and in the induction of
      novel genes during salivary gland development, should provide fruitful areas of
      research for many years.

PMID- 9599293
TI  - Expression of Rhizobium chitin oligosaccharide fucosyltransferase in zebrafish
      embryos disrupts normal development.
AB  - In this report we present data about the effect of the Rhizobium NodZ enzyme on
      zebrafish development. We injected zebrafish embryos with a plasmid expressing
      NodZ protein, and we confirmed that the enzyme is active and has chitin
      oligosaccharide fucosyltransferase (NodZ) activity in vitro. In addition, the
      embryos injected with the NodZ-expressing plasmid, but not with a control
      plasmid, showed malformations or bends in the tail, and in some cases shunted
      tail structures and fused somites. These results clearly indicate that the likely
      substrates for this enzyme, chitin oligosaccharides and free N-glycans, have
      essential functions during early vertebrate embryogenesis.

PMID- 9599294
TI  - Regulation and formation of the Drosophila salivary glands.
AB  - The homeotic gene, Sex combs reduced (Scr), is a master regulator of Drosophila
      salivary gland formation. Embryos in which Scr function is missing do not form
      salivary glands, and embryos in which SCR protein is expressed everywhere form
      extra salivary glands. However, other known proteins, including the homeotic
      protein Abdominal-B, the unusual zinc finger protein Teashirt, and the secreted
      signaling molecule Decapentaplegic (a TGF-beta family member), limit the
      recruitment of SCR-expressing cells to salivary glands. To learn the molecular
      details of how salivary gland gene expression is controlled and as a first step
      toward understanding how the SCR transcription factor controls salivary gland
      morphogenesis, we screened for genes expressed in the developing salivary gland.
      Among our best candidates for potential direct downstream targets of SCR in the
      salivary gland are the genes trachealess (trh), dCREB-A, jalapeno, and Semaphorin
      II (SemaII). Our genetic studies suggest distinct and important roles for each of
      these genes in salivary gland morphogenesis. Current work includes studying the
      molecular interactions between SCR and these downstream target genes and asking
      how target genes coordinate their activities to effect the cell biological
      changes required to build functional salivary glands.

PMID- 9599296
TI  - The role of the insulin-like growth factor I receptor in transformation and
      apoptosis.

PMID- 9599295
TI  - Salivary gland nucleotide receptors. Changes in expression and activity related
      to development and tissue damage.
AB  - Experiments were performed to document the presence of G protein-coupled P2Y
      nucleotide receptors in rat salivary glands and to examine changes in receptor
      expression during development and under conditions in which gland architecture is
      altered. The results indicate that, as opposed to mature rat submandibular gland
      (SMG), immature glands express functional P2Y1 receptors. P2Y1 receptor activity
      was highest at birth and declined over the next four weeks to undetectable
      levels. P2Y1 receptor mRNA levels remained constant over this time course,
      suggesting that receptor activity is regulated at some point other than
      transcription. Conversely, short-term culture of cells from the three major
      salivary glands resulted in upregulation of functional P2Y2 receptors. Responses
      to the P2Y2-selective agonist, UTP, were obtained after 3 h in culture and were
      maximal by 72 hours. This increase was paralleled by increased steady-state P2Y2
      receptor mRNA levels. Upregulation of P2Y2 receptors also occurred in vivo
      following ligation of the main excretory duct of the SMG. These studies suggest
      that nucleotide receptors are dynamically regulated during development and as a
      result of perturbations to gland architecture.

PMID- 9599297
TI  - Apoptosis: a modulator of cellular homeostasis and disease states.
AB  - In normal epithelial tissue, a homeostatic balance is maintained between cell
      replication and apoptosis. Disruption of this balance has serious pathological
      consequences in disease states, such as Sjogren's syndrome, salivary gland
      degeneration, and cancers. Apoptosis may be modulated by cytokine endogenous
      factors and exogenous factors. A vast array of environmental compounds, such as
      differentiating agents and microconstituents found in the diet, initiate
      apoptosis through a redox signal mechanism. In addition to increasing apoptosis,
      these redox signals and transient or permanent changes in cellular redox status
      elevate detoxification enzymes known to protect against many disease states.
      Clearly a further understanding of the regulation of apoptosis and protective
      enzyme elevation by exogenous redox signals will lead to the development of
      future therapeutic strategies against disease.

PMID- 9599298
TI  - Nucleotide sugars, nucleotide sulfate, and ATP transporters of the endoplasmic
      reticulum and Golgi apparatus.
AB  - The lumina of the endoplasmic reticulum and Golgi apparatus are the subcellular
      sites where glycosylation, sulfation, and phosphorylation of secretory and
      membrane-bound proteins, proteoglycans, and lipids occur. Nucleotide sugars,
      nucleotide sulfate, and ATP are substrates in the above reactions and must first
      be translocated from the cytosol into the lumen of these organelles.
      Translocation of these nucleotide derivatives is mediated by highly specific
      transporters, which are antiporters with the corresponding nucleoside
      monophosphate, as shown by genetic and biochemical approaches in mammals and
      yeast. Studies with mammalian, yeast, and protozoa mutants have shown that a
      defect in a specific translocator results in selective impairments of
      glycosylation of proteins, lipids and proteoglycans in vivo. Several of these
      transporters have been purified, cloned, and found to encode very hydrophobic
      proteins with multitransmembrane domains. Experiments with yeast and mammalian
      cells demonstrate that these transporters play a regulatory role in
      posttranslational modifications.

PMID- 9599299
TI  - Development of salivary gland cell lines for studies of signaling and physiology.
AB  - We developed and characterized an immortalized rat parotid cell line to use in
      salivary gland studies. The cells were immortalized by retroviral transduction of
      SV40 large T antigen into isolated parotid cells. Using immunocytochemical
      techniques, we found that the immortalized epithelial cells were ductal, rather
      than acinar, in nature. Cells were grown under coculture conditions with lethally
      irradiated NIH3T3 cells. One cell line, which was designated RPG1/SV40 cells (for
      rat parotid gland 1/SV40 transformant), was selected for characterization. These
      cells formed a sheet epithelium with tight junctions and a measurable
      transepithelial resistance. RPG1/SV40 cells responded to muscarinic receptor
      (carbachol) and/or P2 purinoceptor (ATP and UTP) stimuli with increases in the
      following: (1) intracellular free-calcium concentration ([Ca2+]i); (2) the short
      circuit current (ISC) across the epithelium; (3) the tyrosine phosphorylation of
      PKC delta; and (4) MAP kinase activity. Thus, the cells appear to be useful for a
      wide range of studies involving physiology, biochemistry, and signal transduction
      approaches.

PMID- 9599300
TI  - Transcriptional regulation of salivary proline-rich protein gene expression.
AB  - Mechanisms governing gene expression and regulation in eukaryotes are remarkably
      complex. The results from in vivo transgenic and in vitro transfection studies
      designed to identify cis-element(s) and trans-factor(s) associated with the
      salivary proline-rich proteins (PRPs) gene expression are utilized as a paradigm
      to discuss the regulation of salivary-specific gene expression. Particular
      attention is given to the molecular mechanism(s) underlying the salivary PRP R15
      gene regulation. In rodents, the PRPs are selectively expressed in the acinar
      cells of salivary glands, and are inducible by the beta-agonist isoproterenol as
      well as by dietary tannins. The results from a series of experiments using
      chimeric reporter constructs containing different lengths of the R15 distal
      enhancer region, their mutations, and various expressing constructs are analyzed
      and discussed. These data suggest that the inducible nuclear orphan receptor NGFI
      B may participate in the regulation of salivary acinar cell-specific and
      inducible expression of the rat R15 gene via three distinct distal NGFI-B sites.
      Taken together, a model for the induction of R15 gene expression by isoproterenol
      is proposed. However, the exact molecular basis of this NGFI-B-mediated
      transactivation of cAMP-regulated R15 expression remains to be established.

PMID- 9599301
TI  - Protein secretion by rat parotid acinar cells. Pathways and regulation.
AB  - Protein secretion from rat parotid acinar cells occurs in both the absence and
      presence of secretory agonists. Release takes place by four pathways that are
      distinguished by combined examination of their timing following biosynthetic
      labeling, their relative composition of salivary proteins, and their sensitivity
      to secretagogue stimulation. Following pulse-labeling with a radioactive amino
      acid, two unstimulated export pathways are detected--a constitutive-like pathway
      that is coupled to maturation of secretory granules and the later unstimulated
      exocytosis of secretory granules. In both cases, protein release is insensitive
      to secretory antagonists. Two regulated secretory pathways are also detected. The
      major regulated pathway comprises stimulated exocytosis of secretory granules and
      requires application of beta-adrenergic agonists (> or = 1 microM). A newly
      discovered minor regulated pathway resembles the constitutive-like pathway in
      secretory composition but requires low-dose stimulation by either beta-adrenergic
      or cholinergic agonists. The latter pathway may provide a significant component
      of basal secretion by the parotid gland during periods between meals.

PMID- 9599302
TI  - Salivary abnormalities in Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is characterized by psychomotor and growth
      retardation, infantile hypotonia, characteristic facies, small hands and feet,
      dental abnormalities, and early onset of childhood hyperphagia with consequent
      obesity. PWS is associated with abnormalities of chromosome 15. Approximately 75%
      of patients have a deletion of 15q11q13 on the paternal homologue, whereas 20-25%
      have inherited both chromosome 15s from the mother and none from the father, a
      condition known as maternal uniparental disomy (UPD). Thus, it is a lack of
      paternal alleles in the 15q11q13 region that results in PWS. Thick, sticky saliva
      is a consistent finding in patients with PWS. We have characterized salivary flow
      and composition in individuals with PWS. Salivary flow in patients with PWS is
      approximately 20% of that in controls. In addition, the salivary ions and
      proteins are present in increased amounts, possibly reflecting a concentration
      effect relative to decreased water in the saliva. Both deletion and uniparental
      disomy patients exhibit these findings, suggesting that the gene(s) involved are
      subject to imprinting.

PMID- 9599303
TI  - Acquired salivary dysfunction. Drugs and radiation.
AB  - When considering the effects of drugs on salivary glands, a distinction should be
      drawn between the complaint of oral dryness (xerostomia), a symptom, and
      measurable secretory hypofunction, a sign. In general, the symptom of xerostomia
      is often not accompanied by objective reductions in salivary output, and
      xerostomia is not a reliable indicator of secretory hypofunction. Whereas
      therapeutic pharmaceutical side effects represent the most prominent cause of
      xerostomia, with over 500 drugs associated with this symptom, only a small number
      of drugs have been demonstrated to reduce salivary output substantially. There
      are examples in which drugs with a high prevalence of xerostomia complaints do
      not affect secretory function. The mechanisms responsible for this discrepancy
      between subjective and objective findings have not been fully identified. It is
      hypothesized that alterations in systemic or mucosal hydration may play a role.
      Of the drugs with true salivary hypofunctional actions, most have direct
      anticholinergic properties. In almost all cases, the salivary effects of
      pharmaceuticals are not permanent, and function returns to pretreatment levels
      when the medication is stopped. By contrast, the effects of irradiation on the
      salivary glands are permanent when exposures exceed 50 Gy. About 40,000
      individuals per year receive irradiation that involves the salivary glands (by
      external beam or internal sources--radon implants and 1311) for treatment of
      cancers of the head and neck region. Although these radiation effects have been
      recognized as a significant clinical problem for more than 80 years, the specific
      mechanisms responsible for radiation-induced salivary gland dysfunction are still
      not understood. With the exception of studies documenting the secretory
      functional deficits following head and neck irradiation, limited studies have
      been done in humans. The majority of experimental work has been done in rodents.
      A variety of mechanisms, including mitotic and interphase cell death, direct DNA
      damage or effects of secondary metabolites, damage to progenitor cells, or
      altered gene expression, have all been proposed to explain the salivary
      epithelial cell death observed. Recent experimental studies with models of
      radiation-induced salivary damage in rats and a human salivary cell line suggest
      that the small percentage of surviving epithelial cells are capable of performing
      functions such as signal transduction and ion transport normally. Apoptotic cell
      death following irradiation has not been a prominent feature in these model
      systems. The effects of head and neck radiation on the salivary glands and oral
      cavity continue to present multiple significant clinical problems both during and
      after radiotherapy. In recent years, there has been some progress in minimizing
      these effects through more careful shielding and pretreatment planning.
      Additionally, there are preliminary results from a clinical trial suggesting that
      the use of a secretagogue, pilocarpine HCl, given during the course of
      radiotherapy, may reduce the secretory hypofunctional effects. A multicenter
      trial is now underway to test this hypothesis. There is still a real need to
      develop more effective treatments for this condition.

PMID- 9599304
TI  - Antigen processing and autoimmunity. Evaluation of mRNA abundance and function of
      HLA-linked genes.
AB  - Quantitative defects in the density of conformationally correct human lymphocyte
      antigen (HLA) class I complexes on the surface of lymphocytes are apparent in
      patients with diverse HLA-linked autoimmune diseases, including Type I diabetes
      and Sjogren's syndrome. First, HLA class I expression was investigated in
      individuals with two rare and genetically divergent polyglandular autoimmune
      diseases. Polyglandular failure patients whose disease showed HLA linkage, but
      not those whose disease was not HLA linked, exhibited decreased HLA class I
      expression on the surface of their lymphocytes as well as a reduced abundance of
      transcripts of the HLA-linked genes Tap1 and Tap2, both of which encode proteins
      that contribute to HLA class I processing. Second, lymphocytes from patients with
      insulin-dependent diabetes mellitus (IDDM), Sjogren's syndrome, Graves' disease,
      and Hashimoto's disease showed varying degrees of decreased abundance of mRNAs
      that encode Tap1, Tap2, Lmp2, or Lmp7 (the latter two proteins also contribute to
      HLA class I processing). Third, in twins discordant for IDDM, reduced transcript
      abundance was preferential to diabetic subjects. Fourth, functional assays of
      isolated diabetic proteasomes, the peptide cutting complex containing LMP2 and
      LMP7 proteins, revealed altered peptidase activity. These data suggest that
      defective transcription of HLA class I-processing genes could contribute to the
      quantitative defect in cell-surface expression in autoimmune lymphocytes of HLA
      controlled disease.

PMID- 9599305
TI  - Clinical implications of the dry mouth. Oral mucosal diseases.
AB  - Salivary hypofunction caused by salivary gland disease, medication, or radiation
      may predispose for secondary oral mucosal diseases. In these patients the
      protective coating of saliva is reduced or absent, leaving the oral mucosa more
      vulnerable. Candidiasis, burning mouth syndrome, and white lesions of the oral
      mucosa are increased in frequency. The aim of management is to prevent oral
      pathological changes. The management procedure may include proper oral hygiene,
      saliva-stimulating agents, or saliva substitutes, depending on the severity of
      the salivary dysfunction. Treatment includes antifungal therapy if candidiasis is
      diagnosed. In severely distressed patients, local or systemic corticosteroids may
      be indicated. Precautions, like refraining from smoking and avoiding toothpastes
      containing sodium lauryl sulfate, should also be taken. In the future, agents
      combining antibacterial and antiinflammatory actions, like triclosan, may show
      promising effects in patients with oral mucosal diseases secondary to salivary
      hypofunction.

PMID- 9599306
TI  - Combination gene therapy for salivary gland cancer.
AB  - An established combination gene therapy strategy involving adenovirus vector
      delivery of the herpes thymidine kinase (tk) and murine interleukin-2 genes was
      adapted to treat salivary gland cancer in a murine model. Salivary tumors were
      generated by transcutaneous injection of 5 x 10(5) murine squamous carcinoma
      cells into the submandibular gland of syngeneic C3H/HeJ mice. After one week,
      established submandibular gland tumors were injected with a recombinant
      adenovirus containing therapeutic and control genes. Animals were subsequently
      administered ganciclovir twice daily (25 mg/kg) for six days. All animals
      receiving tk and ganciclovir demonstrated tumor regression, however a
      significantly greater response was seen in mice that were treated with both tk +
      mIL-2. Residual tumors from all treatment and control groups were harvested for
      microscopic evaluation and immunohistochemistry staining. Specific immunostaining
      revealed a predominance of CD8+ lymphocytes in the tumor beds of the animals
      treated with IL-2, suggesting a preferential immune response resulting from the
      local IL-2 expression. Although still in its infancy, the concept or using
      adenoviral gene therapy strategies to provide less invasive means of treating
      salivary tumors is promising.

PMID- 9599307
TI  - Somatic gene transfer to salivary glands.
AB  - Recent developments in gene transfer technology have expanded the range of in
      vivo experimentation and provided new insights that might be applicable to the
      treatment of human diseases. Somatic gene transfer may complement conventional
      transgenic animal experiments by allowing for more restricted gene expression.
      Salivary glands of rats are readily transduced in vivo by adenovirus vectors.
      This model has been used to demonstrate the effects of transferring a water
      channel (aquaporin) gene to glands that have been damaged by radiation.
      Submandibular glands that receive the aquaporin vector increase the stimulated
      salivary flow close to normal levels. The possible role of E2F1 in promoting cell
      regeneration in vivo was also explored. A vector expressing E2F1 was capable of
      increasing DNA synthesis in rat salivary glands, though complete mitosis was not
      observed. Future generations of vectors must overcome current limitations of
      efficiency, immunogenicity, and transient expression.

PMID- 9599308
TI  - Studying development of disease through temporally controlled gene expression in
      the salivary gland.
AB  - Multistep tumorigenesis proceeds through activation of oncogenes and inactivation
      of tumor suppressor genes. Initiating oncoproteins induce secondary changes that
      maintain transformation in the absence of original stimuli. Time-dependent
      reversal of SV40 T antigen (TAg)-induced hyperplasia was studied using temporally
      controlled gene expression. Targeting TAg expression to the submandibular
      salivary gland of transgenic mice produces focal hyperplasias at age two weeks,
      which extend through large areas of the gland by four months. At twelve months,
      fibrosis and tumor foci accompany hyperplasia. Hyperplasia reverses when TAg
      expression in discontinued at four months but not at seven months. Secondary
      changes that maintain transformation appear to be time dependent. The system can
      be used to identify genetic events resulting in phenotypic reversal at four
      months and to expose factors preventing its occurrence at seven months.
      Expression of other proteins can be targeted to the salivary gland, and
      temporally controlled gene deletions can also be made using this system.

PMID- 9599309
TI  - In vitro and in vivo models for the reconstruction of intercellular signaling.
AB  - A critical need in both tissue-engineering applications and basic cell culture
      studies is the development of synthetic extracellular matrices (ECMs) and
      experimental systems that reconstitute three-dimensional cell-cell interactions
      and control tissue formation in vitro and in vivo. We have fabricated synthetic
      ECMs in the form of fiber-based fabrics, highly porous sponges, and hydrogels
      from biodegradable polymers (e.g., polyglycolic acid) and tested their ability to
      regulate tissue formation. Both cell seeding onto these synthetic ECMs and
      subsequent culture conditions can be varied to control initial cell-cell
      interactions and subsequent cell growth and tissue development. Three-dimensional
      tissues composed of cells of interest, matrix produced by these cells, and the
      synthetic ECM (until it degrades) can be created with these systems. For example,
      smooth muscle cells can be grown on polyglycolic acid fiber-based synthetic ECMs
      to produce tissues with cell densities in excess of 10(8) cells/mL. These tissues
      contain extensive elastin and collagen, and the smooth muscle cells within the
      tissue express the contractile phenotype (e.g., alpha-actin staining). Similar
      approaches can be used to grow a number of other tissues (e.g., dental pulp) that
      resemble the native tissue. These engineered tissues may provide novel
      experimental systems to study the role of three-dimensional intercellular
      signaling in tissue development and may also find clinical application as
      replacements to lost or damaged tissues.

PMID- 9599310
TI  - Molecular dissection of the genetic targets of ALG7 in the serpentine receptor
      mediated signal transduction pathway in yeast.
AB  - These initial studies show that deregulated expression of ALG7 affects diverse
      cellular functions crucial to development, including proliferation,
      differentiation, and morphogenesis. Furthermore, the data suggest multiple
      genetic targets for ALG7 and provide the basis for future dissection of these
      developmentally relevant pathways.

PMID- 9599311
TI  - Cholecystokinin as neurotransmitter and neuromodulator in parasympathetic
      secretion in the rat submandibular gland.

PMID- 9599312
TI  - Transfection of COS cells with human cystatin cDNA and its effect on HSV-1
      replication.

PMID- 9599313
TI  - Salivary acidic proline-rich proteins in rheumatoid arthritis.
AB  - In an ongoing attempt to investigate qualitative salivary parameters in diseases
      affecting salivary glands, patients with rheumatoid arthritis (RA) were examined.
      Patients were selected from the Oslo RA register for the present study if they
      fulfilled the following criteria: age 52-74 years, disease duration 10-20 years,
      and disability score as assessed by the Modified Health Assessment Questionnaire
      < or = 2.5. From these 105 patients, two subgroups of patients were selected, one
      group with pronounced sicca symptoms from eyes and mouth, and one group without
      such symptoms. Sicca symptoms were assessed using a postal questionnaire with the
      questions on dry mouth and dry eyes of the European classification criteria for
      Sjogren's syndrome. Patients were excluded from further examinations if they used
      medication that could cause dryness in eyes or mouth. Thus, nine patients
      remained in the sicca group (having four or more sicca symptoms), and ten matched
      RA patients were selected for the nonsicca group. A healthy sex- and age-matched
      control group (n = 10) was also examined. In a preliminary report we have shown
      that differences in flow rates between sicca and nonsicca RA patients were
      limited to lower values of unstimulated whole saliva. To further evaluate
      salivary changes in RA, a disease frequently associated with secondary Sjogren's
      syndrome, we have studied qualitative salivary parameters in these patients,'
      including secretory rates of proline-rich proteins (PRPs), statherins, and
      histatins. In the present report, phenotypes of PRPs, the ratio of PRPs derived
      from the two loci (PRH1 and PRH2), and PRP concentration and output in parotid
      and submandibular saliva derived from the two loci are presented. Parotid (PS)
      and submandibular saliva (SS) were collected from all individuals using 2% citric
      acid as a saliva stimulus. PRPs in PS and SS were identified using a SMART
      microchromatographic system with a Mono Q column and a Tris-HCl/NaCl gradient
      (method adapted from ref. 5). For PRPs, the primary polypeptide products are
      coded for on two loci (PRH1 and PRH2), which have three and two commonly
      occurring gene variants, respectively. On PRH1, the proteins PIF-s, Db-s, and Pa
      are coded for, whereas PRP-1 and PRP-2 are coded for on the PRH2 locus. As each
      protein variant has a postranscriptional cleavage product, individuals will
      exhibit four, six, or eight PRPs in their saliva, depending on whether they are
      homozygous at both, one, or neither of the two loci. Accordingly, 18 possible
      phenotypes may exist, but as few as three phenotypes were found in 79% of the 127
      healthy individuals examined by Hay et al. The SMART system allows the
      determination of the different acidic PRPs present in saliva. Concentrations of
      the various phenotypes were calculated by peak integration versus pure PRP
      standards. Total PRP concentration derived from each locus was calculated as the
      sum of the concentrations of PRP variants from that locus.

PMID- 9599314
TI  - Confocal imaging of gene expression during hamster submandibular gland
      biogenesis.
AB  - The data presented here provide evidence that the abundance of the ALG7 protein
      product, GPT, correlates with high proliferative activity during the postnatal
      development of the hamster SMG development, and that it becomes downregulated
      with differentiation. Based on our previous studies with yeast, changes in the
      level of ALG7 expression may be necessary for the events directing salivary cell
      polarization, migration, differentiation, and apoptosis at distinct developmental
      stages.

PMID- 9599315
TI  - Lacrimal gland functions are differentially controlled by protein kinase C
      isoforms.
AB  - Lacrimal gland protein secretion is primarily under the control of cholinergic
      muscarinic and alpha 1-adrenergic receptors. Cholinergic agonists are coupled to
      the activation of phospholipase C (PLC), which leads to the production of two
      second messenger molecules: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol
      (DAG). IP3 increases the cytoplasmic concentration of calcium ([Ca2+]i), and DAG
      activates protein kinase C (PKC), two events that are thought to trigger protein
      secretion. Lacrimal gland alpha 1-adrenergic receptors are not coupled to the PLC
      pathway, although their activation leads to a slight increase in [Ca2+]i(3). We
      have also shown that unlike the cholinergic receptors, alpha 1-adrenergic
      receptors are not linked to the activation of phospholipase D in lacrimal gland
      acini. Thus the transduction pathway(s) used by the alpha 1-adrenergic receptors
      to trigger lacrimal gland protein secretion remains to be identified. PKC was
      originally described as a Ca2+ and phospholipid-dependent protein kinase
      activated by DAG produced by the receptor-mediated breakdown of
      phosphoinositides. Molecular cloning and biochemical techniques have shown that
      PKC is a family of closely related enzymes consisting of at least eleven
      different isoforms that has been divided into three categories: (1) conventional
      PKCs, including PKC alpha, beta I, -beta II and -gamma isoforms have a Ca2+ and
      DAG-dependent kinase activity; (2) novel PKCs, including PKC epsilon, -delta, 
      theta, -nu, and -mu isoforms, are Ca(2+)-independent and DAG-stimulated kinases;
      (3) atypical PKCs, including PKC zeta, and -iota/lambda isoforms, are Ca2+ and
      DAG-independent kinases. All PKC isoforms, except PKC mu, have a pseudosubstrate
      sequence in their N-terminal part that is thought to interact with the catalytic
      domain to keep the enzyme inactive in resting cells. In previous studies, we
      showed that lacrimal gland acini express three isoforms of PKC: PKC alpha -delta,
      and -epsilon. In the present study, we report the identification of two other PKC
      isoforms, namely PKC mu and -iota/lambda. We show that these isoforms are
      differentially located and that they translocate differentially in response to
      phorbol esters and cholinergic agonists. We also show that PKC isoforms
      differentially control lacrimal gland protein secretion and cholinergic-induced
      Ca2+ elevation. Part of these results has been recently published.

PMID- 9599317
TI  - Presidential address given at the 63rd annual meeting of the American Mosquito
      Control Association, March 1997. The AMCA--review, update, and future course.

PMID- 9599316
TI  - Autoantibodies in salivary hypofunction in the NOD mouse.
AB  - The nonobese diabetic (NOD) mouse exhibits spontaneous salivary gland
      infiltration and loss of salivary function independent of its propensity to
      develop diabetes, and thus can serve as a model for salivary hypofunction in
      Sjogren's syndrome (SS). Studies by others have indicated that this pathology
      depends on lymphocytes and thus may be autoimmune mediated. We have found that
      NOD mice four months of age and older exhibit a 90-95% reduction in pilocarpine
      stimulated salivary flow (5.8 +/- 6.6 mg/5 min) as compared to age- and sex
      matched C57B1/10 controls (98.4 +/- 52.3 mg/5 min). These mice simultaneously
      possess only sparse mononuclear cell infiltrates (averaging approximately one
      small and one large focus per whole-gland section) in the submandibular glands,
      suggesting that loss of salivary function does not require massive infiltration
      of the salivary glands. NOD serum autoantibodies to salivary gland proteins are
      demonstrable by Western blotting, and, as in a subset of SS patients, some NOD
      serum autoantibodies recognize neural antigens. Splenic T-cell reactivity to
      salivary and neural proteins can also be observed. Transfer experiments using NOD
      mouse serum suggest that loss of salivary function, evaluated as a decrease in
      pilocarpine-stimulated flow rate, can be transferred by humoral factors, possibly
      autoantibodies. These results suggest that autoimmune mechanisms dependent on
      both autoantibody and autoreactive T cells can mediate loss of salivary function,
      and that salivary and/or neural antigens may serve as a target for these
      autoimmune reactions.

PMID- 9599318
TI  - Natural habitats of Aedes Aegypti in the Caribbean--a review.
AB  - Natural breeding habitats of Aedes aegypti in the Caribbean region were reviewed
      by conducting larval surveys in Trinidad. Puerto Rico, and the U.S. Virgin
      Islands and referring to records from the Mosquitoes of Middle America project.
      Twelve types of natural habitats were recorded: rock holes (9.7%), calabashes
      (2.4%), tree holes (19.5%), leaf axils (4.8%), bamboo joints (14.9%), papaya
      stumps (7.3%), coconut shells (4.8%), bromeliads (7.3%), ground pools (14.9%),
      coral rock holes (9.7%), crab holes (2.4%), and conch shells (7.3%), of which the
      coconut shell and calabash habitats were new to the Caribbean. The countries
      having the highest prevalence of natural habitats were Trinidad. Puerto Rico, and
      Jamaica, with 9 types (22.0%), 7 types (17.0%), and 6 types (14.6%),
      respectively. The distribution of natural habitats of Ae. aegypti in the
      Caribbean region is discussed in relation to vector control measures.

PMID- 9599319
TI  - Pharmacokinetics, formulation, and safety of insect repellent N,N-diethyl-3
      methylbenzamide (deet): a review.
AB  - This review is intended to provide the reader with an overview of the all-purpose
      topical insect repellent N,N-diethyl-3-methylbenzamide (deet), with emphasis on
      its pharmacokinetics, formulation, and safety aspects. N,N-diethyl-3
      methylbenzamide is effective against a variety of mosquitoes, flies, fleas, and
      ticks, and its protection efficacy depends on factors such as type of
      formulation, application pattern, physical activity of the user, environment, and
      species and feeding behavior of the insects. It offers an inexpensive and
      practical means of preventing the attack of biting insects and, more importantly,
      the transmission of vector-borne diseases. In both humans and animals, deet skin
      penetration and biodistribution are rapid and extensive, and metabolism and
      elimination appear to be complete. As evidenced by over 4 decades of human
      experience and rigorous animal testing, deet is generally safe for topical use if
      applied as recommended, although it has occasionally been related to side effects
      such as toxic encephalopathy, seizure, acute manic psychosis, cardiovascular
      toxicity, and dermatitis, along with a few cases of death due to extensive skin
      absorption. N,N-diethyl-3-methylbenzamide may compete in metabolism with and
      alter the biodistribution properties of other compounds to which a subject is
      simultaneously exposed, resulting in an added risk of side effects. The
      appropriate use of formulation techniques and new formulation excipients not only
      offers a way to extend the duration of protection, but also reduces deet skin
      penetration. In addition to extended repellency, minimal skin penetration of deet
      should be an important consideration in the evaluation of a deet formulation
      during new product development.

PMID- 9599321
TI  - Impact of treatments with Bacillus sphaericus on Anopheles populations and the
      transmission of malaria in Maroua, a large city in a savannah region of Cameroon.
AB  - Simultaneously with a control of breeding sites primarily for Culex
      quinquefasciatus and secondarily for anophelines with Bacillus sphaericus in the
      town of Maroua (120,000 inhabitants) in North Cameroon, a survey of anopheline
      populations and of transmission rates of malaria was performed. Monthly night
      catches in 8 districts of the town emphasized the relation between the biting
      rate by Anopheles in the districts and two main factors. One factor was the
      distance of a district from the breeding sites, i.e., natural flooded areas along
      the periphery of the town or artificial breeding sites (ditches, puddles) filled
      with rain water during the rainy season and with water from the water network
      throughout the year. The second factor was the density of the habitation that
      reduced dispersal of female mosquitoes from the breeding sites and the risk for
      inhabitants to be injected because of scattered bites. The treatment with B.
      sphaericus was followed by a delay (2 months) in the beginning of the
      transmission period and a decrease in the incidence of malaria cases studied in a
      health facility of the town. It thus seems to be possible to reduce malaria
      transmission by applying B. sphaericus to the breeding sites, but this requires a
      good knowledge of the location and dynamics of breeding sites and an improved
      formulation of the pesticide.

PMID- 9599320
TI  - Man-vector contact of phlebotomine sand flies (Diptera: Psychodidae) in north
      central Venezuela as assessed by blood meal identification using dot-ELISA.
AB  - Human bait is traditionally used to assess man-vector contact, which is a key
      point in the study of the epidemiology of vector-borne diseases. However, in
      highly endemic foci, where this method should be avoided, this information could
      be obtained by blood meal analysis of engorged insects. In the village El
      Ingenio, Miranda State, Venezuela, Lutzomyia ovallesi and Lutzomyia gomezi are
      vectors of cutaneous leishmaniasis (CL). From June 1994 to March 1995, sand flies
      were collected inside houses on 974 CDC trap nights from 1900 to 0700 h. A total
      of 7,281 female sand flies were caught: 68.7% of them were identified as L.
      ovallesi, and 3.3% were identified as L. gomezi. Almost all of the blood-engorged
      flies (233 of 237) were dissected and identified, and gut contents were examined
      by dot enzyme-linked immunosorbant assay (dot-ELISA) using antisera against
      humans and common household animals including the domestic mouse. The Human Blood
      Index was 0.817 for L. ovallesi. These results suggest that intradomiciliary
      transmission may occur and account for the cases of CL frequently observed in
      newborn children in El Ingenio.

PMID- 9599322
TI  - Studies on an outbreak of Wesselsbron virus in the Free State Province, South
      Africa.
AB  - In early March 1996, Wesselsbron (WSL) virus caused mortality among lambs on a
      farm near Bultfontein in the northern Free State Province, South Africa. Mosquito
      collections were therefore undertaken from 27 March to 1 April to collect
      floodwater Aedes mosquitoes for attempts at virus isolation. In all, 4,732
      floodwater Aedes were tested; 5 WSL, 1 Middelburg (MID), and 5 unidentified
      viruses were isolated from 3,052 Aedes (Neomelaniconion) mcintoshi/luridus
      (minimum infection rate [MIR] for WSL = 1.63) and 5 WSL, 1 MID, and 3
      unidentified viruses from 1,478 Aedes (Ochlerotatus) juppi/caballus (MIR for WSL
      = 3.38). One of the authors developed WSL fever on 3 April; WSL virus was
      isolated from his serum, and he developed a titer of 1:640 in the
      hemagglutination inhibition (HI) test and became IgM positive against WSL virus.
      Among a sample of 44 sheep bled on 4-5 September, 59% were antibody positive by
      the HI test against WSL and 48% against MID viruses. Mosquito collecting was
      restricted to 2 discrete, shallow, grassy depressions that were the main
      floodwater Aedes breeding sites on the farm so they will be investigated further
      as possible foci of transovarial transmission of WSL and MID viruses.

PMID- 9599323
TI  - Chorionic morphology of eggs of the Psorophora confinnis complex in the United
      States. II. Pre- and postdeposition studies of Psorophora Columbiae (Dyar and
      Knab) eggs.
AB  - Scanning and transmission electron microscopic techniques were used to determine
      the morphology of the exochorion and endochorion of Psorophora columbiae eggs as
      found in the ovary and after deposition. In the ovary, the outer chorionic
      reticulations and tubercles of the eggs are ornately developed below the
      follicular epithelium. Expansion of the eggs after deposition causes the outer
      chorionic reticuli and sculpturing (i.e., minor and major tubercles) to form the
      characteristic spinose appearance of Psorophora eggs. Transmission electron
      microscopic micrographs of cross and sagittal sections of the chorionic layers of
      Ps. columbiae eggs indicate that the major outer chorionic tubercles have 3
      distinct regions. The 3rd region was found only on the dorsum of the tubercle.
      Elevation of major tubercles appears to be regulated, at least in part, by
      ambient moisture conditions, and one function of these tubercles seems to be
      adhesion of the egg to an oviposition surface.

PMID- 9599324
TI  - Preservation of anopheline mosquitoes for DNA probe analysis.
AB  - Anopheles (Cellia) farauti Laveran sensu stricto adults were subjected to a range
      of conditions similar to those experienced by trap-collected mosquitoes prior to
      processing. Squash blots of these specimens were then analyzed using isotopic DNA
      probes. Freezing and thawing 6 times and dry storage on silica gel in a vacuum
      desiccator for up to 180 days did not affect the quality of the DNA. Exposure to
      conditions of high humidity and high temperature for more than 2 h seriously
      reduced the quality of the DNA.

PMID- 9599325
TI  - A method for assessing the effects of runneling on salt marsh grapsid crab
      populations.
AB  - Runneling, a type of habitat modification using shallow channels, is an effective
      method for controlling mosquitoes that breed in intertidal salt marshes. Grapsid
      crab populations were studied to assess the environmental effects of runneling on
      nontarget species. Pitfall traps provided a means of monitoring crab distribution
      and relative abundance at Coomera Island in southeastern Queensland. The study
      indicated that although runneling does not have a significant effect on the total
      number of crabs, it may have a significant impact on species distribution.
      Significantly greater numbers of Parasesarma erythrodactyla were found at the
      runneled site. In contrast, Helograpsus haswellianus was more abundant at the
      unrunneled control site. Associations were also found between species abundance,
      distance from the tidal inlet, and vegetation type. Helograpsus haswellianus was
      associated with mixed vegetation, whereas Parasesarma erythrodactyla was
      associated with tall, dense salt marsh couch. No correlation was found between
      the number of crab burrows present at the study site and the number of crabs
      caught in the traps. However, the runneled site had approximately twice the
      number of crab burrows of the unrunneled control site. These results were
      consistent for 3 consecutive monthly sampling periods. The method has proven
      suitable for further studies on the long-term environmental impact of runneling.

PMID- 9599326
TI  - Laboratory bioassay to compare susceptibilities of Aedes aegypti and Anopheles
      albimanus to Bacillus thuringiensis var. israelensis as affected by their feeding
      rates.
AB  - This study presents the effect of differences in the feeding rates of Aedes
      aegypti and Anopheles albimanus on their susceptibilities to Bacillus
      thuringiensis israelensis. Aedes aegypti was more susceptible than An. albimanus
      because of its faster rate of feeding. Aedes aegypti ingested 11.5 times more
      spores than did An. albimanus, resulting in lower LT50 values. Anopheles
      albimanus larvae fed at a slower rate and required fewer spores than Ae. aegypti
      to induce 50% mortality. These findings support earlier reports of much higher
      concentrations of B. thuringiensis required to kill various anopheline species.

PMID- 9599327
TI  - Bacterial density and survey of cultivable heterotrophs in the surface water of a
      freshwater marsh habitat of Anopheles quadrimaculatus larvae (Diptera:
      Culicidae).
AB  - We examined surface water samples collected in September and October 1994 from a
      freshwater marsh habitat containing larval Anopheles quadrimaculatus mosquitoes.
      Bacterial densities in direct microscopic counts ranged from 9.7 x 10(5) to 1.3 x
      10(7) cells/ml. Densities of cultivable bacteria on trypticase soy agar medium
      ranged from 1.0 to 1.5 x 10(5) cells/ml. The majority of 888 isolates were gram
      positive rods (41%) followed by gram-negative rods (28%). Analysis of the
      cellular fatty acid profiles of 824 isolates using gas chromatography and
      Microbial Identification Systems TSBA (Rev. 3.60) library software grouped the
      bacteria into Bacillus spp. (35%), other gram-positive bacteria (16%),
      pseudomonads (15%), other gram-negative bacteria including mainly
      Enterobacteriaceae and Vibrionaceae (21%), and profiles not recognized (13%).
      Among 33 genera within these groups, the most common were Bacillus, Pseudomonas,
      Aeromonas, and Arthrobacter.

PMID- 9599328
TI  - The lethal effects of Cyperus iria on Aedes aegypti.
AB  - The sedge Cyperus iria, a common weed in rice, contains large amounts of the
      insect hormone (10R) juvenile hormone III (JH III). Given its widespread
      distribution in Asia and Africa, we examined the possibility that C. iria could
      be used as a safe, inexpensive, and readily available mosquito larvicide. Plants
      of varying ages were harvested and leaves tested for lethal effects on larvae of
      the yellow fever mosquito, Aedes aegypti. The median lethal doses (LD50s) for
      frozen leaves from 1- and 2-month-old plants were 267 and 427 mg/100 ml of water,
      respectively. Leaves from 1-month-old C. iria contained 193 micrograms JH III/g
      fresh weight, whereas leaves from 2-month-old plants contained 143 micrograms JH
      III/g fresh weight. Larval sensitivity to the plant differed with age; 4-day-old
      larvae displayed the greatest mortality followed in decreasing sensitivity by
      larvae 5, 6, 3, and 2 days old. Six Cyperus species (C. albostriatus, C.
      alternifolius, C. esculentus, C. iria, C. miliifolius, and C. papyrus) of similar
      developmental stage were assayed for JH III content. Only C. iria was found to
      contain significant levels of JH III.

PMID- 9599329
TI  - Aedes albopictus and the world trade in used tires, 1988-1995: the shape of
      things to come?
AB  - In the decade since used tires were identified as the mode of introduction of
      Aedes albopictus to the United States, similar infestations have been reported
      from 10 other countries in the Americas and 2 in Europe. Millions of used tires
      are still being traded throughout the world and although a few governments have
      implemented inspection procedures to prevent further introductions, these are
      unlikely to be effective. Further introductions of mosquitoes of potential public
      health significance are inevitable.

PMID- 9599330
TI  - Effect of marsh design on the abundance of mosquitoes in experimental constructed
      wetlands in southern California.
AB  - The species composition and abundance of larval mosquitoes were studied in the
      vegetated regions of 2 types of experimental constructed wetlands: one-phase
      marshes, which have continuous vegetation throughout the marsh, and 3-phase
      marshes, which have 2 vegetated regions separated by a region of comparatively
      deeper open water. Larvae of Culex spp. were significantly more abundant in one
      phase marshes than in 3-phase marshes. Larval populations in one-phase marshes
      also contained proportionately more older larval instars (stages III and IV) than
      did populations in 3-phase marshes. Mortality rates of larvae increased during
      the summer and were higher in 3-phase marshes than in one-phase marshes during
      the initial 6 wk of the study. Differences in mortality rates between marsh types
      were related to predator abundance during the first 6 wk of the study and
      thereafter were not strongly associated with predator populations. An infusion of
      decaying bulrush (Schoenoplectus californicus) stimulated oviposition by gravid
      Culex stigmatosoma more than by gravid Culex quinquefasciatus and Culex tarsalis.
      Culex erythrothorax was the most abundant host-seeking species collected in CO2
      baited traps; however, larvae were rarely collected during routine dip sampling
      and egg rafts were never collected in oviposition studies.

PMID- 9599331
TI  - A note on the occurrence of Culex (lophoceraomyia) peytoni and Heizmannia
      (Heizmannia) reidi (Diptera: Culicidae) in Assam, India.
AB  - Culex (Lophoceraomyia) peytoni Bram and Rattanarithikul is recorded for the first
      time from mainland India and Heizmannia (Heizmannia) reidi Mattingly for the
      first time from Assam, in northeast India.

PMID- 9599332
TI  - JC virus excreted by multiple sclerosis patients and paired controls from
      Hungary.
AB  - JC virus (JCV), a human polyomavirus, is the agent of the demyelinating disease
      progressive multifocal leukoencephalopathy (PML). JCV exists in four main
      genotypes in the USA. Type 1, including subtypes Type 1A and Type 1B, makes up
      about 64% of strains in the USA and is thought to be of European origin. Type 2
      is found in Asia, and Type 3 in Africa. A fourth type is found only in the USA.
      In general, these genotypes differ in 1-2.5% of their DNA sequence. Thirty MS
      patients and 30 paired controls from Budapest were studied. The clinical course
      of MS was mainly secondary progressive, and patients were stable at the time of
      testing. Most of the controls were relatives of the probands: a spouse, parent,
      or child. Overall, 25 of 60 (42%) of the urines tested positive for JCV by PCR.
      These included 13 of 30 MS patients, and 12 of 30 controls. Genotyping in the VPI
      gene showed all 25 JCV strains to be Type 1. Among the MS patients, seven were
      Type 1A and six were Type 1B. Among the controls, nine were Type 1A and three
      were Type 1B. In five pairs of MS patients and controls, both were positive for
      JCV by PCR. Two of these were husband/wife pairs of which one pair was matched
      for subtype (both Type 1A), and the other was not. Two of them were
      mother/daughter pairs, and both were matched for subtype (both Type 1B). These
      findings demonstrate that JCV Type 1 predominates among Hungarians, and suggest
      that parent/child pairs can be used to trace JCV transmission within the MS
      family.

PMID- 9599333
TI  - Detection of JC virus DNA in cerebrospinal fluid from multiple sclerosis
      patients.
AB  - JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy
      (PML), has been proposed as a possible aetiopathogenic factor in multiple
      sclerosis (MS). We performed a study to search the LT region of JCV genome by
      nested PCR in cerebrospinal fluid (CSF), peripheral blood mononuclear cell (PBMC)
      and urine samples collected from 121 MS patients, 24 patients with other
      neurological disorders (OND), 30 non neurological patients (NND) and in PBMCs and
      urine of 40 healthy subjects. JCV DNA has been found in the CSF of 11 MS patients
      (9%) while all the CSFs from the 24 OND and the 30 NND cases were negative. No
      significant differences have been observed as regard to the frequency of JCV DNA
      detection in PBMCs and urine between the MS patients and the control groups.
      Nucleotide sequences analysis of seven JCV CSF isolates showed that five strains
      were identical the prototypal strain, while the other two had a base mutation (T-
      >C) in 4286 nucleotide (nt). The finding of JCV DNA in the CSF of MS patients
      suggest that JCV could play a role in the triggering and/or in the maintenance of
      MS aetiopathogenic process, and therefore it should be taken in consideration
      when monitoring this disease.

PMID- 9599334
TI  - Oligodendrocyte and axon pathology in clinically silent multiple sclerosis
      lesions.
AB  - Oligodendrocyte and axon pathology was studied in 11 autopsy cases of clinically
      silent multiple sclerosis. A total of 54 lesions, either demyelinated or late
      remyelinated, were distributed through the whole brain and spinal cord with 39%
      of the lesions located in periventricular areas. Determination of axon density
      revealed an average reduction of 64% and 59% in demyelinated and remyelinated
      lesions with an extreme variation between different plaques and cases.
      Oligodendrocytes were identified by immunocytochemistry for myelin
      oligodendrocyte glycoprotein (MOG) and in situ hybridization for proteolipid
      protein (PLP) mRNA. Oligodendrocytes were almost completely lost in demyelinated
      lesions; remyelinated lesions revealed preservation of a considerable number of
      oligodendrocytes within the lesions. At the border between plaques and the
      periplaque white matter, similar oligodendrocyte numbers as in remyelinated
      lesions were found. Different factors including lesion site, axonal preservation
      and remyelination may thus contribute to the clinical nonappearance of multiple
      sclerosis lesions.

PMID- 9599335
TI  - Immunomodulating functions of recombinant ovine interferon tau: potential for
      therapy in multiple sclerosis and autoimmune disorders.
AB  - The interferons (IFN) are a family of complex proteins possessing antiviral,
      antiproliferative, and immunomodulatory activities. Two type I recombinant human
      IFN have been recently approved for the treatment of multiple sclerosis (MS).
      However, use of high dose type I IFN treatment in MS patients has been limited by
      dose-related toxicity. Ovine IFN tau is a unique type I interferon discovered for
      its role in the animal reproductive cycle. It differs from other type I IFNs in
      that it is remarkably less toxic even at high concentrations, is able to cross
      species barriers, and is not inducible by viral infection. Ovine IFN tau has been
      shown to be very effective in the treatment of animal models of MS. In this
      study, we examined the toxicity of OvIFN tau on human T-cells at high doses and
      its immunregulatory properties at equivalent doses. Our experiments confirmed the
      remarkably non-toxic nature of OvIFN tau on human cells at high concentrations as
      well as immunomodulating properties consistent with other type I IFNs including
      an antilymphoproliferative effect and inhibition of IFN gamma-induced HLA class
      II expression. These results suggest that OvIFN tau could be developed into a
      potentially less toxic therapeutic option for immune-mediated disorders including
      MS.

PMID- 9599336
TI  - Interferon beta-1b injection site reactions and necroses.
AB  - We conducted a comprehensive review of selected adverse event reports that were
      submitted to the Food and Drug Administration (FDA) for interferon beta-1b during
      the first 30 months following licensure. The adverse events reviewed were
      injection site reactions, injection site necroses, and non-injection site
      necroses. These adverse events were selected because of the relative frequency of
      injection site reactions and because of the severity and sequelae of certain
      injection site and non-injection site necroses. Our review enabled us to
      characterize the clinical presentation and the treatment received, which were not
      described in the package insert or by the IFN beta (interferon beta-1b) Multiple
      Sclerosis Study Group publication. The time of onset of the adverse events ranged
      from 1-29 months after initiation of interferon beta-1b treatment, with a mean of
      1 month. In general, the more clinically significant adverse events (i.e.,
      injection site necrosis and non-injection site necrosis) developed more slowly
      than the injection site reactions. Greater than 85% of the adverse events
      presented with one or two signs/symptoms, although the number of signs/ symptoms
      ranged from 1-8. No predominance of treatments for the adverse events was
      observed. The most striking finding was that the overall sex ratio, which could
      be due to reporting artifacts, was 8.1:1 female:male.

PMID- 9599337
TI  - Toxicity in a double-blind, placebo-controlled pilot trial with D-penicillamine
      and metacycline in secondary progressive multiple sclerosis.
AB  - The serine proteinase tissue-type plasminogen activator (t-PA) and the
      metalloproteinase gelatinase B (MMP-9) have recently been demonstrated in MS
      lesions. Both enzymes are interconnected in an enzyme cascade which contributes
      to destruction of the blood brain barrier and demyelination and both enzymes are
      inhibited by D-penicillamine. Metacycline was shown in in vitro experiments to
      inhibit gelatinase B. The combination of peroral D-penicillamine plus metacycline
      was evaluated in a double-blind placebo-controlled way in two groups of 10
      patients suffering from secondary progressive multiple sclerosis. The major
      objectives of this pilot trial were to examine the safety of this combination and
      the possibility of blinding, while the effect on disease progression was
      considered as a secondary endpoint. Over a follow-up period of 1 year and in this
      selected patient group, there was no significant improvement in the Expanded
      Disability Status Scale score (EDSS) as compared with that of the placebo-control
      group. Toxicity was too high to consider additional trials with this combination
      of metalloproteinase inhibitors. Although peroral treatment is by most MS
      patients acknowledged as a major improvement in treatment compliance, one has to
      await the development of more selective and efficacious protease inhibitors than
      those used in the combination therapy described here.

PMID- 9599339
TI  - Integrated care pathways in multiple sclerosis rehabilitation: completing the
      audit cycle.
AB  - The rehabilitation of progressive neurological disorders, such as Multiple
      Sclerosis (MS) requires comprehensive, expert management which is demanding of
      both time and resources. Mechanisms to monitor and audit both process and outcome
      are therefore essential. Integrated care pathways (ICPs) which detail the
      expected interventions during a given episode of clinical care, provide such a
      mechanism. In this study three cohorts of patients (totalling 125 episodes) with
      clinically definite progressive MS underwent a rehabilitation programme audited
      through ICPs. The cohorts were similar in relation to disability and age.
      Variations (departures from the expected pathway) were documented for both the
      rehabilitation process and goal achievement. Duration of stay reduced from 28
      days for the first cohort to 18 days for the third and there was greater
      multidisciplinary input and carer involvement over time. Goal achievement
      increased from 79% for the first cohort to 87% for the third and there was an
      increased emphasis on cognitive function and fatigue management in relation to
      goals set. ICPs provide an excellent mechanism for closing the audit loop and
      have the potential to play an important role in improving service provision in
      MS.

PMID- 9599338
TI  - Computerized color perimetry in multiple sclerosis.
AB  - Color visual field analysis has proven highly sensitive for early visual
      impairments diagnosis in MS, yet it has never attained widespread popularity
      usually because the procedure is difficult to standardize, the devices are
      costly, and the test is fatiguing. We propose a computerized procedure running on
      standard PC, cost effective, clonable, and easy handled. Two hundred and sixty
      four colored patches subtending 1 degree angle vision, with selected hues and low
      saturation levels are sequentially and randomly displayed on gray equiluminous
      background of the PC screen subtending 24 degrees x 40 degrees angle of vision.
      The subject is requested to press a switch at the perception of the stimulus. The
      output provides colored maps with quantitative information. Comparison between
      normals and a selected population of MS patients with no actual luminance visual
      field defects, showed high statistical difference.

PMID- 9599340
TI  - Reader clarifies the use of amphotericin B.

PMID- 9599341
TI  - Reader seeks clarification on the role of glucocorticoids and sodium bicarbonate.

PMID- 9599342
TI  - Nurse commends authors' research on nursing care and clinical trials.

PMID- 9599343
TI  - Aerobic activity should be part of recovery regimen.

PMID- 9599344
TI  - Case in point. Counseling about hormone replacement therapy.
AB  - Mrs. S's case demonstrates the dilemmas that many women face at menopause
      regarding HRT. No clear answer to her question exists. Oncology nurses need to
      help women understand that taking HRT is a decision that is best made after
      carefully weighing the risks and benefits of therapy. Mrs. S needs to realize
      that she has some risk factors for heart disease, osteoporosis, breast cancer,
      and uterine cancer. Depending on her motivation, Mrs. S can modify some of the
      risk factors (e.g., reducing her weight and cholesterol). Smoking cessation also
      would reduce her risk for heart disease and, to a lesser extent, osteoporosis.
      Although her risk for developing breast cancer is higher than for a woman without
      a family history of breast cancer, she only has one relative who was older when
      she developed breast cancer. This risk factor in itself probably would not be
      enough to advise her against taking HRT. Additional testing may offer some
      clarification. If her breasts are difficult to examine or her mammograms are
      difficult to interpret, Mrs. S may feel that the risk of missing breast cancer
      early is too high to justify taking HRT. An abnormal endometrial biopsy also may
      make Mrs. S decide against taking HRT. BMD testing might help to better assess
      her risk for osteoporosis. If some bone loss has occurred before menopause, she
      may want to give more consideration to taking HRT or medications such as
      alendronate sodium to reduce her risk for an osteoporotic fracture. Women need to
      understand that, often, no best answer is available to the question of whether or
      not to take HRT. With every decision comes some consequences. An understanding of
      risk factors and ways to maximize cardiovascular, breast, endometrial, and bone
      health are important factors to consider when making an informed decision.
      Clearly, this is an area where oncology nurses can provide tremendous patient
      education and support to women making decisions about HRT.

PMID- 9599345
TI  - Latex allergy awareness.

PMID- 9599346
TI  - Radioimmunotherapy: special delivery.

PMID- 9599347
TI  - Rituxan: the new kid on the block.

PMID- 9599348
TI  - Nursing care of patients receiving radioactive 131I.

PMID- 9599349
TI  - Outpatient sentinel node biopsy in melanoma.

PMID- 9599350
TI  - Internet cancer support groups: legal and ethical issues for nurse researchers.
AB  - PURPOSE/OBJECTIVES: To explore the legal and ethical issues surrounding the use
      of information obtained from Internet cancer support groups (ICSGs) in research.
      DATA SOURCES: Published articles, news broadcasts, books, government reports.
      DATA SYNTHESIS: ICSGs are a rich source of information for people with cancer,
      their families, caregivers, and nurse researchers. Because ICSGs are new in
      research, potential legal and ethical conflicts in this setting exist.
      CONCLUSIONS: ICSGs are an early prototype of patient groups empowered to seek
      health through the use of information technology. Nurses are ideally suited to
      advance this new area of healthcare technology. Honoring the trust that patients
      have always placed in nurses is essential if this technology is to be developed
      further. IMPLICATIONS FOR NURSING PRACTICE: Given the dearth of guidelines to
      direct researchers, legal and ethical conflicts may occur. Nurse researchers
      should be cognizant of the potential legal and ethical implications involved in
      conducting research via the Internet.

PMID- 9599351
TI  - The revised Piper Fatigue Scale: psychometric evaluation in women with breast
      cancer.
AB  - PURPOSE/OBJECTIVES: To confirm the multidimensionality of the Piper Fatigue Scale
      (PFS) and to reduce the total number of PFS items without compromising
      reliability and validity estimates. DESIGN: Methodologic, part of a larger, cross
      sectional, mailed survey design study. SETTING: Urban and suburban area in the
      northeast United States. SAMPLE: As part of the larger study, 2,250 surveys were
      distributed to women survivors of breast cancer who were on a mailing list for
      the educational organization Living Beyond Breast Cancer, 715 surveys (32%) were
      returned. Of these, 382 women met this methodologic study's criteria for having
      completed each of the 40 items on the PFS. The average respondent was 50 years
      old, postmenopausal, and treated with combination cancer therapy. METHODS:
      Principal axes factor analysis with oblique rotation. MAIN RESEARCH VARIABLES:
      Fatigue factors/subscales. FINDINGS: Five factors/subscales were identified
      initially. Because the fifth factor contained only two items (ability to
      bathe/wash and ability to dress), these items and the associated factor/subscale
      were dropped from the final solution. An additional nine items, not loading on
      any factor (> 0.40), also were dropped. The remaining items and factors/subscales
      were reviewed to ensure that the criteria were met: a pattern of inter-item
      correlations between 0.30-0.70; a minimum number of five or more items/subscale;
      standardized alpha for the subscales and total scale of at least 0.89; and
      absence of gender-specific items. CONCLUSIONS: The revised version of the PFS
      consists of 22 items and four subscales: behavioral/severity (6 items), affective
      meaning (5 items), sensory (5 items) and cognitive/mood (6 items). Standardized
      alpha for the entire scale (n = 22 items) is 0.97, indicating that some
      redundancy still may exist among the items. Additional revisions await further
      testing. IMPLICATIONS FOR NURSING PRACTICE: As fatigue is acknowledged to be the
      most frequent symptom experienced by patients with cancer, accurate measurement
      and assessment is essential to advance not only the science of fatigue but, most
      importantly, to evaluate the efficacy of intervention strategies on patient and
      family outcomes.

PMID- 9599352
TI  - Quality of life of patients with prostate cancer treated with surgery or
      radiation therapy.
AB  - PURPOSE/OBJECTIVES: To compare the quality-of-life (QOL) perceptions of men
      treated for prostate cancer with surgery to those of men treated for prostate
      cancer with radiation therapy. DESIGN: A two-group descriptive study. SETTING:
      Midwestern community cancer center and teaching hospital. SAMPLE: The study group
      consisted of 121 men: 68 treated by radical prostatectomy and 53 treated with
      radiation therapy. METHODS: Mailed survey using the Quality of Life Index (QLI)
      Cancer Version and the University of California at Los Angeles Prostate Cancer
      Index. MAIN RESEARCH VARIABLES: QOL; level of urinary, bowel, and sexual
      function; impact of dysfunction on patients' lives. FINDINGS: No significant
      differences were found between the groups in QLI scores, but significant
      differences were found in urinary, bowel, and sexual function. Urinary function
      was superior in the radiation therapy group (p = 0.0002). Patients who had
      undergone surgery were more likely to leak urine every day (p < 0.001). Only 6%
      of patients who had undergone radiation therapy needed to use pads or diapers as
      compared to 32% of patients who had undergone surgery. Bowel function was better
      in the surgery group (p = 0.05). Both groups reported poor sexual function,
      although it was worse in the surgery group (p = 0.009). CONCLUSIONS: The patients
      who were treated with surgery had significantly worse urinary and sexual function
      and better bowel function than those treated with radiation therapy. QOL scores
      were consistent with these findings, although they did not differ significantly
      between groups. IMPLICATIONS FOR NURSING PRACTICE: This information on the
      problems of survivors of prostate cancer after surgery and radiation therapy and
      the effects of therapy on QOL will assist nurses in providing patient education,
      emotional support, and rehabilitative interventions.

PMID- 9599353
TI  - The controversy of hormone-replacement therapy in breast cancer survivors.
AB  - PURPOSE/OBJECTIVES: To review literature about hormone-replacement therapy (HRT)
      for breast cancer survivors, including potential risks and benefits, long-term
      health outcomes, research directions, and nursing's role in counseling these
      patients. DATA SOURCES: Journal articles, abstracts, text excerpts. DATA
      SYNTHESIS: HRT after menopause delivers proven benefits, including decreased risk
      of cardiovascular disease and osteoporosis and improved quality of life (QOL). As
      more women survive breast cancer, health risks resulting from treatment-induced
      menopause must be considered. Breast cancer survivors traditionally have not been
      offered HRT out of fear of cancer reactivation. This prohibition is being
      reexamined as data accumulate about estrogen's benefits. CONCLUSION: Further
      prospective research is needed to develop criteria for the prudent use of HRT
      after breast cancer. IMPLICATIONS FOR NURSING PRACTICE: Nurses can develop
      standards for patient education about HRT options and, when they are prescribed,
      design appropriate tools to measure HRT's impact on QOL, symptom relief, and long
      term health outcomes.

PMID- 9599354
TI  - The Schwartz Cancer Fatigue Scale: testing reliability and validity.
AB  - PURPOSE/OBJECTIVES: To describe the psychometric development of the Schwartz
      Cancer Fatigue Scale (SCFS). DESIGN: A multiphase instrumentation study
      describing construct and operational definitions, informal and formal content
      validity, reliability, and validity analysis. SAMPLE: Content validity
      established with 20 subjects. Reliability and validity evaluated with 166
      subjects residing in diverse parts of the United States. FINDINGS: Eleven items
      that failed to show variance, had high interitem correlations, or failed to
      discriminate were eliminated. Factor analysis resulted in a four-factor solution
      that accounted for 70% of the variance. Cronbach's alpha for the total scale was
      estimated to be 0.96 and to be between 0.82 and 0.93 for the subscales.
      CONCLUSIONS: The 28-item SCFS has demonstrated reliability and content and
      construct validity. Factor analysis supports the four subscales (physical,
      emotional, cognitive, and temporal). Preliminary construct validity has been
      demonstrated by differences in fatigue between those people who are currently
      receiving treatment and those who have completed treatment and by scores on a
      visual analogue scale of fatigue. IMPLICATIONS FOR NURSING PRACTICE: The SCFS may
      prove to be clinically relevant in assessing the effect of interventions to treat
      and manage cancer-related fatigue.

PMID- 9599355
TI  - Hereditary nonpolyposis colon cancer: genetic basis, testing, and patient-care
      issues.
AB  - PURPOSE/OBJECTIVES: To describe the general mechanisms of cancer development and
      the specific genetic basis for hereditary nonpolyposis colon cancer (HNPCC); to
      discuss methods of genetic testing, surveillance, and management guidelines; and
      to review relevant psychosocial issues. DATA SOURCES: Published papers, research
      reports, and books. DATA SYNTHESIS: Colorectal cancer is one of the most common
      neoplasms in humans and perhaps the most frequent form of hereditary neoplasia.
      HNPCC has an autosomal dominant pattern of inheritance with variable but high
      penetrance estimated to be about 90%. HNPCC underlies 0.5%-10% of all cases of
      colorectal cancer. CONCLUSIONS: An understanding of the mechanisms behind the
      development of HNPCC is emerging, and genetic presymptomatic testing, now being
      conducted in research settings, soon will be available on a widespread basis for
      individuals identified at risk for this disease. Complex medical, nursing, legal,
      ethical, and psychosocial issues demand oncology nurses' attention and
      understanding. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses in all settings
      play an integral role assisting patients in (a) understanding their genetic risk
      status and the implications of genetic testing, (b) making decisions regarding
      HNPCC genetic predisposition testing, and (c) understanding the meaning of DNA
      test results. Nurses also may assist patients in understanding and complying with
      recommended surveillance and management issues.

PMID- 9599356
TI  - Differences in outcomes among patients experiencing different types of cancer
      related pain.
AB  - PURPOSE/OBJECTIVES: To determine differences in pain characteristics, mood
      states, and quality of life (QOL) in outpatients with different types of cancer
      related pain (i.e., somatic, visceral, or neuropathic) compared to outpatients
      who were pain-free. DESIGN: Descriptive, comparative. SETTING: Sixteen outpatient
      facilities that are part of the Oncology Nursing Research Network. SAMPLE: A
      convenience sample of 129 outpatients who experienced cancer-related pain and 169
      pain-free patients, all of whom were actively being treated for cancer. METHODS:
      All patients completed a demographic questionnaire, the Multidimensional Quality
      of Life Scale-Cancer, and the Profile of Mood States, Patients with pain
      completed a Cancer Pain Questionnaire and the McGill Pain Questionnaire.
      Patients' medical records were reviewed. MAIN RESEARCH VARIABLES: Types of cancer
      related pain (i.e., somatic visceral, or neuropathic), pain intensity, pain
      duration, quality of pain, QOL, and mood states. FINDINGS: No differences were
      found in any pain characteristics or any pain indices from the word descriptors
      of the McGill Pain Questionnaire. Patients with somatic and visceral pain had
      significantly higher fatigue scores than pain-free patients. In addition,
      patients with somatic and visceral pain had significantly lower physical well
      being, nutrition, and total QOL scores and more symptom distress than pain-free
      patients. CONCLUSIONS: The type of cancer-related pain appears to influence the
      mood states and QOL of outpatients with cancer. IMPLICATIONS FOR NURSING
      PRACTICE: Oncology nurses need fo determine the type of pain the patient is
      experiencing and the impact of the pain on the patient's mood and QOL.

PMID- 9599357
TI  - Choosing reconstruction after mastectomy: a qualitative analysis.
AB  - PURPOSE/OBJECTIVES: To describe women's perspectives on factors that influenced
      their decision to have reconstructive surgery after a breast cancer diagnosis.
      DESIGN: Exploratory, descriptive, qualitative study. SETTING: A comprehensive
      cancer center in an urban setting. SAMPLE: Eleven women who underwent mastectomy
      and reconstruction. Six participants had autologous transverse rectus abdominis
      musculocutaneous-flap reconstruction, four had saline implants, and one had a
      silicone implant. All but one reconstruction was performed at the time of
      mastectomy. METHODS: Open-ended, face-to-face interviews using an interview guide
      were conducted within one month of reconstruction. One to two follow-up
      interviews were conducted approximately six months later. MAIN RESEARCH
      VARIABLES: Decision making about reconstruction, perceptions of information needs
      and sources, sources of support, and factors important to decision making.
      FINDINGS: The main theme identified was Getting My Life Back. The participants
      described this in terms of the themes of Information Seeking, Talking It Over,
      and Seeking Normality. The interactive skills of the healthcare provider played
      an important role in the women's decision making. CONCLUSIONS: Reconstruction
      minimized the negative consequences of breast cancer and its treatment for the
      women in the study. The decision-making process was aimed at getting the person's
      life back as close to what it was before the diagnosis as possible or improving
      it. The three themes of decision making are interactive in nature, with
      participants returning to information Seeking and Talking It Over as necessary to
      increasing their understanding and clarifying their "normality goals."
      IMPLICATIONS FOR NURSING PRACTICE: Healthcare professionals should determine how
      a woman wants to participate in decision making as well as the kind, amount, and
      sources of information the individual with breast cancer wants to have to make
      her decisions. Healthcare providers are key sources of information about
      treatment options, and they are critical to patient satisfaction with the
      decision-making process and with the final results of the surgical procedure.
      Family members, friends, and other women with breast cancer play a crucial role
      in talking it over.

PMID- 9599358
TI  - Coping with a partner's cancer: adjustment at four stages of the illness
      trajectory.
AB  - PURPOSE/OBJECTIVES: To study the psychosocial adjustment of partners/spouses of
      patients with cancer at four specific stages of the illness trajectory time of
      diagnosis, period of first remission, first recurrence, and period of metastatic
      disease. DESIGN: A cross-sectional, descriptive survey. SETTINGS: A university
      cancer center, a private cancer clinic, and a clinic in a large city serving
      people who are uninsured and unable to pay for their treatment. SAMPLE: 175
      partners of patients who were in one of four specific stages of the illness
      trajectory participated in this study, Various types of cancer were represented.
      Seventy-seven participants were men, and 98 were women; their mean age was 49
      years. METHODS: A survey questionnaire was used to collect data on psychosocial
      adjustment, specific sources of social support, dyadic adjustment, coping
      strategies, emotional response, cognitive response, and personal control.
      FINDINGS: Results indicate that partners of patients who were experiencing a
      recurrence of their illness or who were in the metastatic stage of the disease
      were more vulnerable to increased distress and problems of adjustment. Women also
      reported higher levels of distress than men. Variables that had the most
      significant direct affect on adjustment were emotional response, cognitive
      response, family support, and partner cohesion. Coping strategies influenced
      emotion and cognition. CONCLUSIONS: Caring for partners is essential to promoting
      quality of life for the patient and the family. IMPLICATIONS FOR NURSING
      PRACTICE: Assessment, providing an opportunity to express concerns, and referral
      for psychosocial intervention as necessary are important to promote the highest
      possible quality of life for partners and patients.

PMID- 9599359
TI  - Physical and psychosocial outcomes of midlife and older women following surgery
      and adjuvant therapy for breast cancer.
AB  - PURPOSE/OBJECTIVES: To investigate the patterns of functioning and psychosocial
      adjustment of midlife and older women following surgery for breast cancer.
      Differences between those who received follow-up adjuvant therapy and those who
      did not also were compared. DESIGN: 2 x 3 mixed design with one between-groups
      factor (type of treatment) and one within-subjects factor (time). SETTING: Four
      midwestern hospitals. SAMPLE: 46 patients with breast cancer who are age 55 or
      older. METHODS: Baseline data about presurgical functional status and other
      variables were obtained during the first week after surgery. Follow-up data were
      obtained at six weeks, three months, and six months postsurgery. Data were
      collected via telephone interviews and mailed questionnaires. MAIN RESEARCH
      VARIABLES: Functional status, patient symptomatology, quality of life (QOL),
      demands of illness, and type of treatment (surgery only versus surgery plus
      adjuvant therapy). FINDINGS: No differences existed between the two treatment
      groups at baseline, with the exception of lower functional status reported by the
      surgery-only group. In the surgery-only group, functional status improved
      significantly from six weeks to three months postsurgery. The most frequently
      reported symptoms of both groups included fatigue and pain. CONCLUSIONS: These
      results suggest that both groups did equally well, regardless of whether they
      received adjuvant therapy (radiation or chemotherapy). Neither QOL nor demands of
      illness differed between the two groups, nor did these scores change
      significantly over time following surgery. IMPLICATIONS FOR NURSING PRACTICE:
      These findings suggest that women undergoing surgery for breast cancer, whether
      they receive adjuvant therapy or not, may have functional and psychosocial needs
      that could be effectively addressed by nursing interventions pre- and
      postsurgery.

PMID- 9599361
TI  - Pars plana vitrectomy, lensectomy, or extraction in transscleral intraocular lens
      fixation for the management of dislocated lenses in a family with Marfan's
      syndrome.
AB  - BACKGROUND AND OBJECTIVES: Congenital lens subluxation may be a difficult
      therapeutic problem. Surgical treatment options include iris manipulation or lens
      decision, aspiration, intracapsular or extracapsular extraction, and lensectomy
      through the pars plana. It is not established which kind of aphakic correction is
      the most appropriate in these cases. PATIENTS AND METHODS: A father and his two
      sons with Marfan's syndrome were operatively treated for lens dislocation in both
      eyes. Pars plana vitrectomy was done in all eyes. Dislocated lenses were removed
      by lensectomy in three eyes and with an intracapsular method in three eyes. The
      outside-in scleral fixation technique was used for primary posterior chamber
      intraocular lens (PC IOL) implantation in all cases. RESULTS: All eyes achieved
      good visual acuity (20/20-20/25). Time of observation ranged between 8 and 20
      months. There were no intraoperative or post-operative complications. CONCLUSION:
      Pars plana vitrectomy and primary scleral-fixated IOL implantation is a safe
      procedure and gives good visual rehabilitation in adult patients with Marfan's
      syndrome.

PMID- 9599360
TI  - A prospective randomized trial of topical soluble 0.1% indomethacin versus 0.1%
      diclofenac versus placebo for the control of pain following excimer laser
      photorefractive keratectomy.
AB  - BACKGROUND AND OBJECTIVE: To compare the safety and efficacy of topical
      nonsteroidal antiinflammatory drugs (NSAIDs) for the control of pain after
      excimer laser photorefractive keratectomy (PRK). PATIENTS AND METHODS: One
      hundred twenty informed patients were enrolled in a double-masked, randomized,
      comparative study and assigned to either 0.1% indomethacin, 0.1% diclofenac, or
      placebo treatment. Subjective postoperative pain, symptoms, re-epithelialization
      rate, and systemic medications were monitored for 2 days following photoablation.
      RESULTS: Compared with the placebo, 0.1% indomethacin solution significantly
      reduced pain on the day of surgery (D0) (P < .05), whereas 0.1% diclofenac did
      not reach a significant level (P = .46). At D0, analgesic intake by the oral
      route was significantly greater in the placebo group (P < .05). Severe
      photophobia was significantly less frequent in the group treated with 0.1%
      indomethacin (P < .05). Corneal wound healing was significantly delayed in the
      patients treated with 0.1% diclofenac at D2 as compared with other groups (P =
      .04). CONCLUSION: Topical 0.1% indomethacin solution helps control the pain
      induced by excimer laser photoablation of the cornea without any detrimental
      effect to the corneal epithelial wound healing.

PMID- 9599362
TI  - Reproducibility of the laser flare meter and laser cell counter in assessing
      anterior chamber inflammation following cataract surgery.
AB  - BACKGROUND AND OBJECTIVES: To determine the interobserver and intraobserver
      reproducibility of the laser flare meter and laser cell counter in assessing
      anterior chamber inflammation following cataract surgery. PATIENTS AND METHODS:
      Thirty-nine eyes with varied degrees of inflammation and 9 normal eyes were
      included in the study. Anterior chamber flare and cells were evaluated with the
      slit lamp and graded on a scale of 0 to 4+. The flare and cells were then
      measured three times each using the flare meter and cell counter by two
      different, experienced observers. The intraobserver reproducibilities were
      computed to evaluate repeatability of the instruments operated by the same
      observer. The first measurement taken by each observer was used to assess
      reproducibility between the two observers. RESULTS: The intraobserver
      reproducibility for overall flare was 0.995 for both observers. The intraobserver
      reproducibility for overall cells was 0.996 for observer 1 and 0.991 for observer
      2. The overall interobserver reproducibility was 0.994 for flare and 0.988 for
      cells. The correlation between measurements and slit-lamp ratings was 0.78 for
      flare and 0.56 for cells. CONCLUSIONS: The intraobserver and interobserver
      reproducibilities were excellent, with good correlation to slit-lamp
      measurements. Reproducible results can be obtained using the laser flare meter
      and the laser cell counter. It is not known whether these results are applicable
      to other inflammatory processes with higher grades of flare and cells and with
      different protein and cell types.

PMID- 9599363
TI  - Indocyanine green angiography patterns of zones of relative decreased choroidal
      blood flow in patients with exudative age-related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To investigate the incidence and patterns of posterior
      zones of relative decreased choroidal blood flow in patients with exudative age
      related macular degeneration. PATIENTS AND METHODS: Digital indocyanine green
      (ICG) angiograms from 100 patients with exudative age-related macular
      degeneration were reviewed for the presence of posterior zones of relative
      decreased choroidal blood flow. The patterns of these zones and their location
      relative to the choroidal neovascular process were noted. RESULTS: Ninety-five
      percent of the angiograms displayed the presence of either a complete or an
      incomplete zone of relative choroidal hypoperfusion. The zone was most apparent
      in the early frames of the angiogram. Five different patterns of relative
      decreased choroidal blood flow were identified: horizontal (32%), vertical (14%),
      bipartite (9%), tripartite (31%), and quadripartite (9%). The choroidal
      neovascular process was located within or at the edge of the zone of relative
      choroidal hypoperfusion in all cases. CONCLUSION: Most cases of choroidal
      neovascularization localize to areas of relative choroidal dye nonfilling on ICG
      angiography. These patterns of choroidal nonfilling may have implications in the
      pathogenesis and management of choroidal neovascular membranes in age-related
      macular degeneration.

PMID- 9599364
TI  - Intraocular pressure during pneumatic retinopexy.
AB  - BACKGROUND AND OBJECTIVE: A simplified method of monitoring intraocular pressure
      (IOP) during pneumatic retinopexy was devised and used clinically to decrease the
      risk of complications associated with unnecessary IOP elevation. PATIENTS AND
      METHODS: Intraoperative IOP and IOP immediately after sulfur hexafluoride (SF6)
      injection were monitored during pneumatic retinopexy in 22 eyes with
      rhegmatogenous retinal detachment. Intraoperative IOP was measured with a
      sphygmomanometer connected to the side of a gas-filled syringe. RESULTS:
      Intraoperative IOP and IOP immediately after gas injection were 97.2 +/- 28.5
      (mean +/- SD) and 46.5 +/- 19.6 mm Hg, respectively. Two eyes temporarily lost
      light perception immediately after the gas injection. The intraoperative IOP and
      the IOP immediately after the gas injection were 130 and 80 mm Hg, respectively,
      in one eye, and 180 and 90 mm Hg, respectively, in the other. CONCLUSIONS: In
      general, to ensure effective and safe results of pneumatic retinopexy, the
      authors recommend that the gas be injected either to approximately 90 mm Hg of
      intraoperative IOP or to the maximum acceptable volume (2.0 to 2.5 ml of 100%
      SF6).

PMID- 9599365
TI  - Radiation therapy for uveal malignant melanoma.
AB  - The treatment of uveal melanoma is controversial. The treatment methods include
      enucleation and other techniques designed to preserve the eye, such as local
      resection, plaque radiotherapy, charged particle radiotherapy, laser
      photocoagulation, and thermotherapy. Plaque radiotherapy and charged particle
      radiotherapy provide tumor control and patient survival comparable with
      enucleation. Plaque radiotherapy may be associated with fewer anterior segment
      complications, but the posterior segment complications appear to be similar using
      either plaque radiotherapy or charged particle radiotherapy. Thermotherapy is
      emerging as an important adjuvant treatment to maintain control of uveal melanoma
      after radiotherapy.

PMID- 9599366
TI  - Quantification of holmium: YAG and thulium: YAG laser-induced scleral shrinkage
      for buckling procedures.
AB  - BACKGROUND AND OBJECTIVE: To quantify and compare holmium:YAG (2.1 microns) and
      thulium:YAG (2.0 microns) laser-induced scleral shrinkage for retinal buckling
      procedures. MATERIALS AND METHODS: Two overlapping spots of either laser
      radiation were applied at the equatorial sclera of 50 human cadaver eyes. Scleral
      shrinkage was expressed as a relative change of length between two reference
      points on the scleral surface, and quantified as a function of energy per pulse,
      total energy, scleral thickness, and intraocular pressure (IOP). Tissue effects
      were studied histopathologically. RESULTS: Shrinkage was most dependent on total
      fluence and attained a maximum of 27% to 30% with an IOP of 4 mm Hg, regardless
      of scleral thickness or laser parameters, but decreased with increasing IOP. The
      thulium:YAG laser produced more efficient scleral shrinkage and less collagen
      damage than the holmium:YAG laser. CONCLUSION: The recommended parameters for
      laser-induced scleral shrinkage are the thulium:YAG laser, with 2.4 J/cm2 per
      pulse and 12.0 to 14.4 J/cm2 total fluence (5 to 6 pulses). IOP control (< or = 4
      mm Hg) is crucial during laser scleral buckling.

PMID- 9599368
TI  - Myopia, hypotony, and lenticular shift following strabismus surgery.
AB  - A 5-year-old girl had hypotony, myopia, and anterior displacement of the lens
      iris diaphragm following routine strabismus surgery. This constellation of
      findings suggests that surgical manipulation of the intact sclera produced a
      limited effusion involving the supraciliary space. Following cycloplegia, these
      findings resolved over several weeks, suggesting that this rare complications is
      self-limited and associated with a good prognosis for recovery.

PMID- 9599367
TI  - Presumed choroidal granuloma with vitreous hemorrhage resembling choroidal
      melanoma.
AB  - This report describes a presumed choroidal granuloma with vitreous hemorrhage
      resembling choroidal melanoma. A healthy 31-year-old man, who had progressive
      vision loss in the right eye during 1 month, was found to have a yellow-white
      juxtapapillary choroidal mass. Fluorescein angiography demonstrated a choroidal
      neovascular membrane over the lesion. There was focal persistent hypofluorescence
      in the late phase of fluorescein angiography. The thickness of the lesion
      increased from 3.0 mm to 7.1 mm during 1 month. Subretinal and vitreous
      hemorrhage developed. The patient was suspected to have a choroidal granuloma and
      choroidal neovascular membrane, and was treated with oral steroids. Ten months
      later, the vitreous blood cleared completely with an attached retina. Control of
      inflammation may have a role in the treatment of idiopathic choroidal granulomas
      and some choroidal neovascular membranes secondary to ocular inflammation.

PMID- 9599369
TI  - Trabeculectomy with the use of amniotic membrane for uncontrollable glaucoma.
AB  - Although trabeculectomy is an established surgical technique for glaucoma, in
      some cases it does not achieve a good filtering effect despite the use of
      mitomycin-C (MMC). The authors have developed a new surgical technique for
      uncontrollable glaucoma that uses amniotic membrane to prevent postoperative
      adhesion of conjunctiva and sclera. They performed trabeculectomy with a limbal
      based conjunctival flap using 0.4 mg/ml of MMC for 2 minutes. Amniotic membrane
      was then placed under the scleral flap and sutured using 10-0 nylon. Among 14
      eyes of 13 patients who underwent this procedure, intraocular pressure was
      controlled to less than 20 mm Hg after surgery in 13 eyes, including 3 eyes that
      underwent a second surgery with the same technique and 2 eyes that underwent
      laser trabeculoplasty. The authors' results suggest that this technique is
      efficacious for the reduction of intraocular pressure in high-risk glaucoma
      patients.

PMID- 9599370
TI  - Management of the Molteno silicone tube in corneal transplant surgery.
AB  - A method to prevent tube-corneal touch in patients with Molteno implants who
      require corneal transplants is presented. A double-armed 10-0 Prolene suture is
      passed from limbus to limbus so that within the anterior chamber the suture acts
      as a splint for the silicone tube of the Molteno implant, keeping it away from
      the cornea. This suture has been used in six patients, all aphakic or
      pseudophakic, requiring corneal transplants for bullous keratopathy. In all six
      patients, the silicone tube was successfully splinted away from the endothelium
      of the corneal transplant.

PMID- 9599371
TI  - Ultrasound-guided cryotherapy for retinal tears in patients with vitreous
      hemorrhage.

PMID- 9599372
TI  - Comanagement.

PMID- 9599373
TI  - Mary O'Malley, M.D.

PMID- 9599374
TI  - Josephine Jackson, M.D.

PMID- 9599375
TI  - Marie Briehl and Rosetta Hurwitz: lay analysts and American psychoanalysis.

PMID- 9599376
TI  - Lucile Dooley, M.D.

PMID- 9599377
TI  - Clara Thompson as culturalist.

PMID- 9599378
TI  - Edith B. Jackson, M.D.

PMID- 9599379
TI  - Martha Wolfenstein: toward the severance of memory from hope.

PMID- 9599380
TI  - Ruth Easser, M.D.

PMID- 9599381
TI  - Some applications of psychiatry and psychoanalysis to social issues.

PMID- 9599382
TI  - Advanced MR imaging techniques for evaluation of the heart and great vessels.
AB  - A "one-stop shop" for evaluating cardiac disease with magnetic resonance (MR)
      imaging is progressing toward clinical reality and promises to have a major
      effect on the care of patients with cardiac disease. T1-weighted conventional
      spin-echo imaging gated to the cardiac cycle yields good anatomic detail but
      requires long imaging times and provides only static images of a single cardiac
      phase. Fast MR imaging with electrocardiographically (ECG) gated, low-flip-angle,
      segmented k-space gradient-recalled-echo (GRE) sequences provides excellent image
      quality with sufficiently high temporal resolution to "freeze" cardiac motion.
      Segmented k-space sequences improve on standard ECG-gated GRE sequences by
      allowing many cardiac phases, or frames of a cine sequence, to be imaged in a
      single breath hold with prospective cardiac gating. As commercial implementations
      of segmented k-space imaging become more widely available, the applications of
      this technique are expanding from research protocols to include many clinical
      applications in the heart and great vessels. Such applications include evaluation
      of vascular anatomy (coronary angiography, aortic disease, aberrant vessels,
      vascular access), cardiac anatomy (congenital anomalies, right ventricular
      dysplasia, constrictive pericarditis, valvular function), myocardial perfusion,
      and myocardial wall motion.

PMID- 9599383
TI  - CT angiography of potential renal transplant donors.
AB  - Renal transplantation has grown rapidly over the past 30 years, resulting in an
      inadequate supply of organs to meet the ever-increasing demand. This has led to
      an increase in the number of living-related donors. Advances in imaging
      technology now allow safe, rapid, and relatively noninvasive evaluation of
      potential donors. Helical computed tomographic (CT) angiography is a fast,
      minimally invasive procedure that is quickly becoming the imaging modality of
      choice for preoperative evaluation of potential renal transplant donors. Helical
      CT, combined with low-osmolar intravenous contrast materials, has enabled CT
      angiography to depict arterial and venous anatomy accurately. Between July 1995
      and March 1997, CT angiography was performed in 205 potential renal donors.
      Correlation with surgical findings in 136 donor nephrectomies helped confirm a
      high level of accuracy for CT angiography in the assessment of the renal
      vasculature: Sensitivity and specificity for identifying specific vessels was
      99.6% and 99.6% for main renal arteries, 76.9% and 89.9% for polar arteries, and
      98.7% and 95.5% for main renal veins, respectively. CT angiography allows the
      radiologist to provide the transplant surgeon with precise preoperative anatomy
      of the renal vasculature, thus reducing the risks and complications associated
      with the harvesting procedure and improving the chances for a successful outcome.
      However, accurate radiologic interpretation depends on the radiologist's
      experience level, attention to detail, and commitment to careful image
      evaluation.

PMID- 9599384
TI  - Role of CT angiography in the preoperative evaluation for laparoscopic
      nephrectomy.
AB  - Laparoscopic nephrectomy (LN) was recently introduced as a minimally invasive
      alternative to open nephrectomy in living related renal donation. Because of the
      limited field of view available with laparoscopic techniques, the role of
      preoperative radiologic evaluation in LN has expanded to include anatomic
      definition of the renal arteries, collecting system, renal parenchyma, and renal
      venous anatomy. Computed tomographic (CT) angiography has proved to be a
      minimally invasive alternative to conventional angiography in the preoperative
      evaluation of living related renal donors. CT angiography has been shown to have
      an accuracy comparable to that of conventional angiography in predicting renal
      arterial anatomy. In addition, CT angiography provides comprehensive definition
      of the renal vascular anatomy including the location, size, and length of the
      renal, adrenal, gonadal, and lumbar veins. Dual-phase spiral CT combined with
      three-dimensional CT angiography constitute a single, minimally invasive
      procedure that can provide a complete preoperative evaluation of potential living
      related renal donors prior to LN. Comprehensive anatomic depiction of the renal
      arterial and venous supplies aids in surgical planning and helps avoid potential
      complications.

PMID- 9599385
TI  - Helical CT of potential living renal donors: toward a greater understanding.

PMID- 9599386
TI  - Complications associated with transcatheter arterial embolization for hepatic
      tumors.
AB  - Transcatheter arterial embolization (TAE) is widely used in the treatment of
      hepatic tumors. A total of 2,300 TAE procedures were performed with a 2-15-mL
      injection of a mixture or suspension of anticancer drugs and iodized oil,
      followed by administration of gelatin sponge particles. One or two
      chemotherapeutic drugs, including doxorubicin hydrochloride (10-30 mg),
      epirubicin hydrochloride (10-30 mg), mitomycin C (10-20 mg), and cisplatin (25
      100 mg), were used for each procedure. Complications were encountered in 4.4% of
      cases (n = 102) and were related to the use of chemoembolic agents or the
      manipulation of a catheter or guide wire. These complications included acute
      hepatic failure (n = 6), liver infarction (n = 4) or abscess (n = 5),
      intrahepatic biloma (n = 20), multiple intrahepatic aneurysms (n = 6),
      cholecystitis (n = 7), splenic infarction (n = 2), gastrointestinal mucosal
      lesions (n = 5), pulmonary embolism or infarction (n = 4), tumor rupture (n = 1),
      variceal bleeding (n = 3), and iatrogenic dissection (n = 35) or perforation (n =
      4) of the celiac artery and its branches. Knowledge of these complications is
      important for correct diagnosis and appropriate management.

PMID- 9599387
TI  - CT-guided interventional procedures for pain management in the lumbosacral spine.
AB  - The lumbosacral spine is the source of pain, suffering, and disability more
      frequently than any other part of the body. Pain in the lower back can be managed
      with computed tomography-guided analgesic interventional procedures, such as
      periradicular infiltration, percutaneous laser disk decompression, facet joint
      block, and percutaneous vertebroplasty. Periradicular injection of steroids
      provides short-term and sometimes even long-term relief of low back pain.
      Percutaneous laser disk decompression is used to treat radiculalgia caused by
      disk herniation. Facet joint block is useful in diagnosis and treatment of facet
      syndrome. Percutaneous vertebroplasty provides short- and long-term pain relief
      in patients with vertebral body disease. However, precise patient selection is
      essential to the success of each of these techniques. The interventional
      radiologist has an active role to play in minimally invasive management of lower
      back pain and should be part of an interdisciplinary team that determines the
      appropriate therapy.

PMID- 9599388
TI  - Diagnostic imaging of ventriculoperitoneal shunt malfunctions and complications.
AB  - Most pediatric patients with hydrocephalus are treated with ventriculoperitoneal
      (VP) shunt placement. However, shunt malfunction is common and is usually caused
      by mechanical failure. Shunt obstructions may be confirmed with radioisotope
      examination or with fluoroscopically guided injection of iodinated contrast
      material into the shunt reservoir. Disconnections or breaks are more readily
      detected at radiography in cases in which barium-impregnated shunt tubing was
      used. Migration and leakage may also occur. Cerebrospinal pseudocysts may be
      demonstrated with plain radiography and further evaluated with computed
      tomography (CT) and sonography. In increasing hydrocephalus, plain radiography
      may reveal sutural diastasis and increased cranial cavity size, and CT can be
      used to evaluate ventricle size. In cases of enlarging intracranial cysts,
      injection of iodinated contrast material followed by CT can help document a
      connection between the cyst and the ventricles. Ventriculitis and meningitis can
      be visualized at CT and magnetic resonance imaging as enhancement of the
      ventricular ependymal lining or cerebral cortical sulci. Other complications
      associated with VP shunts include surgery-related complications, shunt
      overdrainage and slit-ventricle syndrome, neoplastic metastasis, pleural
      effusion, and complications related to shunt variants. Imaging analysis is an
      essential adjunct to the clinical evaluation of patients with suspected VP shunt
      malfunctions or complications. Radiologists should be familiar with these
      potential problems and the diagnostic utility of various imaging modalities.

PMID- 9599389
TI  - The perihippocampal fissures: normal anatomy and disease states.
AB  - Understanding the three-dimensional anatomy of the perihippocampal fissures
      (PHFs) can be helpful in making the correct diagnosis of diseases of the mesial
      temporal lobe. Disorders of the parenchyma and cerebrospinal fluid spaces are
      reflected by specific changes in the PHFs. A marker for Alzheimer disease and
      mesial temporal sclerosis is atrophy of the hippocampus and associated dilatation
      of the PHFs. This finding is best visualized on coronal magnetic resonance images
      but can and should be appreciated on routine computed tomographic scans.
      Hydrocephalus is characterized by dilatation of the temporal horn of the lateral
      ventricle without dilatation of the transverse fissure and its extensions. Normal
      pressure hydrocephalus can usually be distinguished from Alzheimer disease on the
      basis of the pattern of dilatation of the PHFs. Understanding the anatomy of the
      PHFs often makes it possible to better characterize the extents of intra- and
      extraaxial tumors of the mesial temporal lobe.

PMID- 9599390
TI  - Extrinsic and intrinsic ligaments of the wrist: normal and pathologic anatomy at
      MR arthrography with three-compartment enhancement.
AB  - The ligaments of the wrist have been demonstrated with magnetic resonance (MR)
      imaging by many authors. Distinction has been made between the extrinsic, or
      radiocarpal and ulnocarpal, ligaments and the intrinsic, or intercarpal,
      ligaments. The stability of the wrist depends on numerous ligaments: The volar
      ligaments are important stabilizers of the wrist, whereas the dorsal ligaments
      are less crucial for wrist stability. An MR imaging protocol that demonstrates
      these structures with high resolution has been developed. Cadaveric wrists are
      imaged with a spoiled gradient-recalled-echo volume-acquisition technique with
      fat suppression after three-compartment enhancement with a contrast agent
      containing gadolinium. The specimens are then sectioned, and the anatomic and
      pathologic findings are correlated with the findings on the MR images. The
      extrinsic and intrinsic ligaments of the wrist are clearly demonstrated with this
      technique. This protocol was designed for anatomic study and promotes
      understanding of the anatomy and biomechanics of the wrist; it is not intended
      for clinical use.

PMID- 9599391
TI  - The Rocky liver: radiologic-pathologic correlation of calcified hepatic masses.
AB  - Although relatively uncommon in daily clinical practice, calcification may be
      found in inflammatory hepatic lesions and in benign and malignant liver
      neoplasms. The most common source of calcified hepatic lesions is inflammatory
      conditions such as granulomatous diseases (e.g., tuberculosis). The calcification
      typically involves the entire lesion and appears as a dense mass that can produce
      artifacts on computed tomographic (CT) scans. Echinococcus cysts have curvilinear
      or ring calcification. Hemangiomas, especially large ones, may contain large,
      coarse calcifications that are centrally located in areas of fibrosis; these may
      be seen at CT (20% of cases) or radiography (10%). In hepatocellular adenoma,
      calcifications may be solitary or multiple and are usually located eccentrically
      within a complex heterogeneous mass. Calcifications in fibrolamellar carcinoma
      have been reported in 15%-25% of cases at CT and occur in a wide variety of
      patterns. Calcifications in intrahepatic cholangiocarcinoma are typically
      accompanied by a desmoplastic reaction and are visible at CT in about 18% of
      cases. Calcified hepatic metastases are most frequently associated with mucin
      producing neoplasms such as colon carcinoma. Knowledge of the pathologic features
      of each entity helps radiologists to better recognize the shape, size, density,
      number, location, and distribution of hepatic calcifications seen on images and
      to narrow the differential diagnosis.

PMID- 9599392
TI  - Pulmonary angiitis and granulomatosis: radiologic-pathologic correlation.
AB  - Five distinct clinical syndromes of pulmonary angiitis and granulomatosis are
      currently recognized: Wegener granulomatosis, lymphomatoid granulomatosis,
      necrotizing sarcoid granulomatosis, bronchocentric granulomatosis, and allergic
      angiitis and granulomatosis (Churg-Strauss syndrome). Patients typically present
      in middle age with fever, cough, hemoptysis, dyspnea, or chest discomfort. Upper
      airway involvement such as sinusitis suggests Wegener granulomatosis. Medical
      renal disease is associated with Wegener granulomatosis and Churg-Strauss
      syndrome. Asthma may be present in bronchocentric granulomatosis and Churg
      Strauss syndrome. Pathologic examination of these entities demonstrates
      vasculitis, granulomatous inflammation, and parenchymal necrosis. The radiologic
      manifestations of pulmonary disease are varied, but the most typical appearance
      is that of multiple nodules or masses that may demonstrate cavitation. Diffuse
      multifocal air-space opacities with or without cavitation may also be seen.
      Pulmonary hemorrhage is a well-known presenting manifestation of Wegener
      granulomatosis and, less commonly, of Churg-Strauss syndrome. Because of the
      multifocal lung involvement in these diseases, pulmonary metastases and
      infectious causes are often considered in the differential diagnosis. Affected
      patients are treated with cytotoxic agents and corticosteroids. The prognosis is
      variable, depending on the specific syndrome, but may be favorable in the absence
      of significant complications.

PMID- 9599393
TI  - Percutaneous intervention in acute pancreatitis.
AB  - Interventional radiology has an important role to play in the management of local
      complications of acute pancreatitis, such as necrosis, pseudocyst, and abscess.
      Computed tomography (CT) is preferred for guiding pancreatic interventional
      procedures, with the most common access routes being through the left anterior
      pararenal space for pancreatic tail collections and through the gastrocolic
      ligament for pancreatic head and body collections. Pancreatic necrosis has a high
      mortality if infected, and the presence of infection must be determined with CT
      guided needle aspiration. Careful planning of the access route is important to
      avoid the colon. Catheters of 8-12 F are usually sufficient for pseudocyst
      drainage. An average of 2-3 weeks drainage is required if there is no
      communication of the pseudocyst with the pancreatic duct and many weeks to months
      for pseudocysts with pancreatic duct communication. Percutaneous drainage of
      pseudocysts is associated with success rates of 80%-90%. Pancreatic abscess
      drainage has quoted success rates varying between 32% (infected necrosis) and 90%
      (pancreatic abscess). Use of large or multiple catheters is often required for
      complete drainage. The management of patients with severe acute pancreatitis is
      time-consuming and labor intensive for interventional radiologists, and a team
      approach with close communication with surgical personnel is required.

PMID- 9599394
TI  - Clinical applications of basic x-ray physics principles.
AB  - The application of basic x-ray physics principles to clinical radiography
      requires consideration of many factors that have complex interrelationships. For
      any given radiographic examination, proper understanding and application of each
      of these factors is essential. The exposure factors--tube voltage, tube current,
      and exposure time--determine the basic characteristics of radiation exposure to
      the patient and image receptor. In addition, equipment factors (focal spot size,
      grid use, x-ray generator design) and geometry (source-object distance and source
      image receptor distance) also influence patient dose and the quality of the
      radiograph. The basis for evaluation of exposure parameter selection is the
      optimization of image quality, including contrast, density, motion unsharpness,
      and geometric unsharpness, while minimizing patient exposure. Selection of
      radiographic technique often involves consideration of trade-offs between various
      measures of image quality and exposure.

PMID- 9599395
TI  - Chest radiographic image quality: comparison of asymmetric screen-film, digital
      storage phosphor, and digital selenium drum systems--preliminary study.
AB  - Conventional screen-film radiography does not display all regions of the thorax
      satisfactorily. Three chest radiographic techniques display both the lung and the
      mediastinum with good contrast. These techniques are asymmetric screen-film
      (ASF), digital storage phosphor (DSP), and digital selenium drum (DSD) imaging.
      ASF systems use two asymmetric screen-film combinations to produce a wide
      latitude image of the thorax with good contrast in the lungs. In DSP systems,
      image data are acquired digitally with a wide dynamic range by using the optical
      output of a photostimulable phosphor plate; in DSD systems, the wide-range
      digital image data are acquired by using the electronic charge generated on a
      drum coated with a thin layer of amorphous selenium. The appearance of a DSP or
      DSD radiograph is then determined by user-selected image processing operations:
      tone scaling, spatial frequency processing, and dynamic range compensation.
      Digital chest radiographs processed with strong regional equalization provide
      both excellent contrast in the lungs and effective display of the mediastinum and
      chest wall. At visual comparison, the high lung contrast and good mediastinal,
      retrocardiac, and subdiaphragmatic detail provided by the DSD method distinguish
      it from the other two methods.

PMID- 9599396
TI  - Reproduction of radiologic images on plain paper.
AB  - Skyrocketing health care costs and pressures from managed care have combined to
      promote cost-cutting strategies in radiology and radiation oncology departments.
      A study was conducted to evaluate the use of a high-resolution laser printer for
      printing plain-paper images as substitutes for both original and duplicate
      radiologic film images. A variety of radiologic images were used to evaluate the
      image reproduction capabilities of the printer in terms of linearity, detail, and
      contrast. In many cases, printed images had a quality comparable to that of the
      original images. Six computed tomographic (CT) scans and six radiation therapy
      simulator radiographs were compared with printed reproductions by each of seven
      board-certified radiation oncologists, who rated the reproductions as acceptable
      for documentation, acceptable for diagnostic purposes (CT scans only), or
      unacceptable. Ninety-five percent of printed CT images and 90% of printed
      simulation images were rated acceptable for documentation. The quality of printed
      images of radiation therapy port films was not quantitatively measured but was
      improved by adjusting image contrast and brightness and using various image
      enhancement techniques. The use of printed images is less expensive than that of
      processed film and eliminates the environmental, time, storage, and delivery
      problems associated with film. Technologic advances in imaging, networking, and
      printing have made possible the inexpensive duplication of medical images.

PMID- 9599397
TI  - Virtual bronchoscopy for three--dimensional pulmonary image assessment: state of
      the art and future needs.
AB  - Virtual bronchoscopy is emerging as a useful approach for assessment of three
      dimensional (3D) computed tomographic (CT) pulmonary images. A protocol for
      virtual bronchoscopic assessment of a 3D CT pulmonary image would have two main
      stages: (a) preprocessing of image data, which involves extracting objects of
      interest, defining paths through major airways, and preparing the extracted
      objects for 3D rendering; and (b) interactive image assessment, which involves
      use of graphics-based software tools such as surface-rendered views, projection
      images, virtual endoscopic views, tube views, oblique section images, measurement
      data, global two-dimensional section images, and cross-sectional views. Although
      a virtual bronchoscope offers a unique opportunity for exploration and
      quantitation, it cannot replace a real bronchoscope. Limitations of current
      virtual endoscopy systems include high cost, lack of visual aids beyond simulated
      endoscopic views, difficulty in performing interactive anatomic exploration, lack
      of quantitative information, use of surface rendering instead of volume
      rendering, and need for substantial off-line display computation. Future needs
      include development of fully integrated user-friendly virtual bronchoscopes,
      development of optimal CT protocols for generating artifact-free data sets, and
      improvements in automated preprocessing of 3D CT images.

PMID- 9599398
TI  - Benign metastasizing leiomyoma in the lung.

PMID- 9599399
TI  - Breast imaging case of the day. Benign intraductal papilloma with focal atypical
      papillomatous hyperplasia.

PMID- 9599400
TI  - Pediatric case of the day. Osteosarcomatosis or metastatic osteosarcoma.

PMID- 9599401
TI  - US case of the day. Renal leiomyoma.

PMID- 9599402
TI  - Neuroradiology case of the day. Myxopapillary ependymoma of the conus medullaris
      or filum terminale resulting in superficial siderosis and dissemination of tumor
      along CSF pathways.

PMID- 9599403
TI  - General case of the day. Acute intrapericardial diaphragmatic hernia.

PMID- 9599404
TI  - Nutritional aspects of the development of cancer. Report of the Working Group on
      Diet and Cancer of the Committee on Medical Aspects of Food and Nutrition Policy.

PMID- 9599405
TI  - Extracellular degradation of agonists as an adaptive mechanism.
AB  - Many cellular responses are initiated by the binding of an extracellular ligand
      to receptors at the cell surface. The removal of these ligands, or agonists,
      would therefore be expected to contribute to the process by which cells recover
      from stimulation. While dilution in the extracellular medium reduces the
      concentration of most agonists, many cells have developed specific mechanisms for
      removing particular ligands. One of the more effective mechanisms is to degrade
      the extracellular agonist and here we review the production and action of the
      enzymes responsible for the degradation of a number of these agonists.

PMID- 9599406
TI  - G protein-coupled receptor adaptation mechanisms.
AB  - G protein-coupled receptors (GPCRs) transduce extracellular signals that modulate
      the activity of a wide variety of biological processes, such as
      neurotransmission, chemoattraction, cardiac function, olfaction, and vision.
      However, GPCR signalling desensitizes rapidly as the consequence of receptor
      phosphorylation. G protein-coupled receptor kinase-mediated receptor
      phosphorylation promotes the binding of beta-arrestin proteins, which not only
      uncouple GPCRs from their cognate heterotrimeric G protein, but also target them
      for endocytosis. The sequestration (endocytosis) of desensitized GPCRs to
      endosomes is required for their dephosphorylation and subsequent resensitization
      to their pre-ligand exposed state. This review concentrates on the mechanisms
      underlying GPCR desensitization and resensitization.

PMID- 9599407
TI  - Down regulation of yeast G protein-coupled receptors.
AB  - G protein-coupled receptors are essential components of the pheromone signaling
      pathway in Saccharomyces cerevisiae. When ligands bind to these receptors, their
      down regulation is stimulated. The sequence of events in this process is proposed
      to be the following: ligand-induced conformational change, receptor
      hyperphosphorylation and ubiquitination, internalization by an actin-dependent
      mechanism and subsequent delivery through at least two endocytic intermediates to
      the vacuole where the receptors are degraded.

PMID- 9599408
TI  - Regulation of G protein signalling in yeast.
AB  - A common property of cell signaling systems is the ability to adapt to chronic
      stimulation. A genetic analysis of receptor/G protein signaling in yeast has led
      to the identification of a new class of regulators of G protein signaling (RGS
      proteins), as well as to new insights about the regulatory role of G protein
      modifications (myristoylation, palmitoylation). Similar modes of regulation are
      now known to exist in humans. These discoveries fill some important gaps in our
      understanding of signal transduction, and provide an instructive example of how
      model organisms, like yeast, can provide new insights relevant to signal
      regulation in higher eukaryotes.

PMID- 9599409
TI  - Protein phosphatases and the regulation of MAP kinase activity.
AB  - A family of dual specificity (Thr/Tyr) MAP kinase phosphatases (MKPs) have been
      identified in mammalian cells. These enzymes are implicated in negative feedback
      control of MAP kinase activity. This idea is supported by genetic and biochemical
      evidence which implicates homologous enzymes in the regulation of MAP kinases in
      yeasts and Drosophila. However, recent work in yeasts has shown that, in addition
      to these dual specificity MKPs, 'classical' tyrosine-specific phosphatases are
      also involved in the regulated dephosphorylation of MAP kinases. A picture is
      emerging in which a complex interplay between upstream activators and multiple
      protein phosphatases is responsible for the regulation of MAP kinase activity.
      The activities, substrate specificities and subcellular localisation of these
      protein phosphatases are likely to be key determinants of the biological outcome
      of signalling through different MAP kinase pathways in mammalian cells and
      tissues.

PMID- 9599410
TI  - Phosphatidylinositol signalling reactions.
AB  - Phosphatidylinositols are important in intracellular signaling. In response to
      extracellular signals, these molecules undergo rapid turnover and generate second
      messengers including diacylglycerol, inositol 1,4,5-trisphosphate,
      phosphatidylinositol 3,4-bisphosphate (PtdIns 3,4P2) and phosphatidylinositol
      3,4,5-trisphosphate (PtdIns 3,4,5-P3). The importance of phosphoinositide
      metabolism is underscored by its link to a human genetic disorder
      oculocerebrorenal syndrome of Lowe in that the gene product (OCRL) deficient in
      this syndrome is an inositol polyphosphate 5-phosphatase. A new pathway for
      formation of PtdIns 3,4-P2 and PtdIns 3,4,5-P3 has been found recently. PtdIns
      4,5-P2-synthesizing enzymes phosphatidylinositol 4-phosphate 5-kinases (PIP5K)
      also have kinase activity towards PtdIns 3-P and PtdIns 3,4-P2 forming PtdIns 3,4
      P2 and PtdIns 3,4,5-P3 respectively. Surprisingly, they can synthesize PtdIns
      3,4,5-P3 directly from PtdIns 3-P in a concerted reaction. PIP5K isozymes may
      play pivotal roles in intracellular signaling.

PMID- 9599411
TI  - Adaptation in cyclic AMP signalling processes: a central role for cyclic AMP
      phosphodiesterases.
AB  - Cyclic AMP has provided the paradigm for the second messenger concept. Recent
      evidence has identified a complex array of isoforms of the enzymes involved in
      generation, destroying and transmitting the effects of this second messenger.
      These proteins provide a sophisticated system for organising cAMP signal
      transduction in specific intracellular compartments; for allowing integration
      with other signalling systems and for controlling the kinetics and hence reaction
      characteristics of cAMP signal transduction.

PMID- 9599412
TI  - On the relationship between the plant cell and the plant.
AB  - The mechanism by which higher plant cells divide is quite different from the
      animal system, and has implications for the way in which the processes of pattern
      formation, morphogenesis and cell differentiation are executed. The relationship
      between cell shape, cell division and differentiation and development will be
      considered from an evolutionary perspective, and the ways in which new molecular
      markers can inform our interpretation of these relationships will be considered.

PMID- 9599413
TI  - Polarity determination in Fucus: from zygote to multicellular embryo.
AB  - Zygotes of fucoid algae acquire polarity de novo. The initial polarity
      establishes the apical-basal polarity of the multicellular embryo and the adult
      plant. Acquisition of polarity involves the translation of external vectorial
      signals into spatial information within the cell via spatial photoreceptor
      activation at the level of the plasma membrane. Fixation of the polar axis
      involves interactions between the cytoskeleton, plasma membrane and the cell
      wall. Recently a central role for targeted secretion in polar axis fixation has
      been identified. In the multicellular embryo, evidence is accumulating for roles
      of cell wall and intercellular communication via diffusible signals in pattern
      formation and control of cell fate.

PMID- 9599414
TI  - Pattern formation in plant embryogenesis: a reassessment.
AB  - Pattern formation in embryogenesis generates the basic body plan of flowering
      plants by establishing the diversity of position-dependent cell fates
      characteristic of the seedling. The concept of pattern formation, which was
      originally based on the analysis of Arabidopsis pattern mutants, is re-examined
      in the light of recent data that address the origin of the axis of polarity, the
      origin of the primary meristems as elements of the apical-basal pattern and the
      formation of the radial pattern of tissue layers. The available evidence from
      genetic, molecular and experimental approaches supports the notion that embryonic
      pattern formation occurs in steps involving communication between clonally
      unrelated cells.

PMID- 9599415
TI  - Cell fate regulation in the shoot meristem.
AB  - The shoot meristem is a proliferative centre containing pluripotent stem cells
      that are the ultimate source of all cells and organs continuously added to the
      growing shoot. The progeny of the stem cells have two developmental options,
      either to renew the stem cell population or to leave the meristem and to
      differentiate, possibly according to signals from more mature tissue. The destiny
      of each cell depends on its position within the dynamic shoot meristem. Genetic
      data suggest a simple model in which graded positional information is provided by
      antagonistic gene functions and is interpreted by genes which regulate cell fate.

PMID- 9599416
TI  - Root pattern: shooting in the dark?
AB  - Root pattern formation takes place in the embryo and is propagated through
      subsequent growth and development of the seedling root meristem. Pattern is
      maintained by positional cues and in some cases by local cell interactions. Such
      interactions are involved in the balance between cell division and
      differentiation in cells neighbouring the quiescent centre. This balancing act
      also occurs in the shoot in which the genetic circuitry underpinning this
      phenomenon has been characterised. The common genetic mechanism of patterned cell
      differentiation in the epidermis between the root and shoot extends these
      parallels further. Given that these shared mechanisms exist, it is tempting to
      speculate that they reflect the fact that roots may be derived, shoot structures.
      Alternatively such mechanisms may reflect an evolutionary convergence of genetic
      mechanism.

PMID- 9599417
TI  - Early events in leaf development.
AB  - Morphological studies of early events in leaf development have been hindered by
      the lack of stereotypic patterns of cell division and markers for cell identity.
      However, molecular genetic analysis, particularly in maize, has begun to suggest
      the mechanisms which partition meristematic cells into a leaf primordium, define
      regional identities within the primordium and direct localised growth which leads
      to outgrowth and flattening of the leaf. Therefore, the leaf may provide a model
      for pattern formation applicable to other parts of the plant.

PMID- 9599418
TI  - Spatial regulation of trichome formation in Arabidopsis thaliana.
AB  - Trichomes in Arabidopsis are single-celled hairs that develop from epidermal
      cells regularly distributed on leaves, sepals and stems. Trichome formation in
      Arabidopsis is emerging as a genetic and molecular model system for the analysis
      of the spatial regulation of cell type specification in plants. In this review we
      focus on two aspects of trichome initiation: the regulation of organ and tissue
      layer specificity and the establishment of an epidermal spacing pattern.

PMID- 9599419
TI  - Patterning the floral meristem.
AB  - Flowers are reproductive structures unique to the angiosperms. Flowers, which
      develop from small mounds of cells called floral meristems, show a number of
      universal patterns such as the arrangement of organs of different type along the
      floral axis. However, other conserved patterns, such as floral asymmetry, are
      merely conserved within different subgroups. This review discusses the emerging
      picture of early operating developmental mechanisms, which pattern floral
      meristems along the radial and dorsiventral axes, and of later-acting ones, which
      pattern tissue differentiation within floral organs.

PMID- 9599420
TI  - The molecular and genetic basis of ovule and megagametophyte development.
AB  - The formation of ovules is a key step in the plant life cycle which alternates
      between a diploid and haploid generation, the sporophyte and the gametophyte. The
      transitions between the two generations in the female occur in the ovule, the
      site of meiosis, female gametogenesis and double fertilization. The intimate
      association of sporophytic and gametophytic tissues in the ovule allows an
      investigation of their cellular interactions during ovule and seed development.
      In Arabidopsis, several sporophytically acting loci which primarily affect the
      morphogenesis of the integuments have been identified. Early acting genes may
      respond to positional information leading to a region-specific initiation of
      morphogenesis, whereas later acting genes affect cellular aspects of integument
      growth. Much less is known about the mechanisms controlling the development of
      the megagametophyte. Comparative morphology and genetic analyses suggests that
      regulatory mechanisms ensure a tight coordination of independently controlled
      cellular processes with cell specification and differentiation.

PMID- 9599421
TI  - Motivational interviewing: an intervention tool for child welfare case workers
      working with substance-abusing parents.
AB  - Child welfare case workers have long known that abuse of alcohol and drugs is a
      major problem with many parents on their caseloads. This article discusses
      motivational interviewing, an intervention technique used with substance abusers.
      Motivational interviewing, which is based on the principles of motivational
      psychology, postulates that motivation is created in an interaction between the
      client and worker. Principles of motivational interviewing are discussed and
      illustrated in a case example.

PMID- 9599422
TI  - Home alone and other inadequately supervised children.
AB  - This study examined the relationship between a mother's motivation, capacities,
      and opportunities, and how much supervision her children received. Ninety-five
      mothers who adequately supervised their children were compared with a
      demographically comparable sample of 37 mothers who did not. Mothers who provided
      inadequate supervision were less motivated, had fewer problem-solving and social
      skills, and were more likely to move, be homeless, and have inadequate housing.
      No differences were found between the groups on perceived social support.
      Families with supervision problems tended to have an adult or child in the family
      with one or more problems. A discriminant analysis showed that less education and
      poorer problem-solving skills made the largest contribution to the function.

PMID- 9599423
TI  - Advances in the diagnosis and treatment of children with serious mental illness.
AB  - As a nation, we are becoming aware that a significant number of children develop
      severe neuropsychiatric disorders. Unfortunately, knowledge of DSM-IV criteria
      does not always help the child and family social worker identify children with
      these disorders. Early onset schizophrenia, bipolar disorders, and severe
      depression can cause child behaviors that differ markedly from symptoms
      manifested by adults with serious mental illness. This article provides specific
      information for screening and treating children who develop long-term
      neuropsychiatric disorders.

PMID- 9599424
TI  - Sibling incest: treatment of the family and the offender.
AB  - Sibling incest takes place in the context of a family system that does not
      provide a safe environment for its members. Treatment should encompass all
      pertinent aspects of the family system and the roles of all the family members
      within it, and intact boundaries must be created. Hierarchical realignment
      diminishes enmeshed subsystems and produces more open, honest communication in
      the family. The offender must take responsibility for his or her behavior. This
      stance should be supported by the parents. All family members should adhere to a
      safety plan throughout the treatment process.

PMID- 9599425
TI  - The ecology of endoparasitic helminth infections of brown trout (Salmo trutta)
      and rainbow trout (Oncorhynchus mykiss) in Scotland.
AB  - Two hundred and forty brown trout (Salmo trutta) and 49 rainbow trout
      (Oncorhynchus mykiss), obtained from 21 locations in Central Scotland between
      October 1990 and August 1993, were examined for endoparasitic helminth
      infections. Crepidostomum farionis (Digenea) was the most widely distributed
      helminth species, followed by Eubothrium crassum (Cestoda), Diphyllobothrium
      dendriticum and D. ditremum (Cestoda), Neoechinorhynchus rutili (Acanthocephala),
      Echinorhynchus truttae (Acanthocephala), Eustrongylides sp. (Nematoda),
      Capillaria salvelini (Nematoda), Cyathocephalus truncatus (Cestoda),
      Raphidascaris acus (Nematoda) and Cystidicola farionis (Nematoda), in that order.
      The prevalences and intensities of each helminth infection were recorded. No
      evidence was found to indicate that even fish with the highest worm burdens (e.g.
      339 plerocercoids of Diphyllobothrium spp.) were experiencing any obvious
      morbidity. An analysis of pairs of associations between species of helminths
      revealed a significantly positive association between N. rutili and C. farionis
      (P < 0.01). The results are discussed in terms of patterns in helminth
      communities in freshwater fish.

PMID- 9599426
TI  - Cenotes (sinkholes) of the Yucatan Peninsula, Mexico, as a habitat of adult
      trematodes of fish.
AB  - Examination of a total of 581 fish specimens of 15 species from 39 cenotes
      (sinkholes) in the Yucatan Peninsula, southeastern Mexico, revealed the presence
      of 10 species of adult trematodes. These were as follows: Saccocoelioides
      sogandaresi Lumsden, 1963, Saccocoelioides sp. (family Haploporidae),
      Cichlasotrema ujati Pineda et Andrade, 1989 (Angiodictyidae), Crassicutis
      cichlasomae Manter, 1936 (Homalometridae), Magnivitellinum simplex Kloss, 1966
      (Macroderoididae), Stunkardiella minima (Stunkard, 1938) (Acanthostomidae),
      Oligogonotylus manteri Watson, 1976 (Cryptogonimidae), Genarchella tropica
      (Manter, 1936), G. astyanactis (Watson, 1976), and G. isabellae (Lamothe
      Argumedo, 1977) (Derogenidae). Saccocoelioides sogandaresi is reported from
      Mexico for the first time. Poecilia velifera and P. latipunctata for S.
      sogandaresi, Cichlasoma octofasciatum for C. cichlasomae, Cichlasoma
      friedrichstahli and C. meeki for O. manteri, and C. meeki, C. octofasciatum and
      Gobiomorus dormitor for G. isabellae represent new host records. Most species
      found are described and figured and their host range and distribution are
      discussed.

PMID- 9599427
TI  - Experiments on second intermediate fish host related cercarial transmission of
      the eyefluke Diplostomum spathaceum into rainbow trout (Oncorhynchus mykiss).
AB  - The effect of host variables such as size and density, on the transmission of
      cercariae of Diplostomum spathaceum (Rudolphi, 1819) into a second intermediate
      fish host, rainbow trout, Oncorhynchus mykiss (Walbaum), was studied
      quantitatively in laboratory experiments under varying exposure conditions.
      Differences in the number of established metacercariae were noted in differently
      sized fish exposed singly to the same number of cercariae and in water volumes
      related to the body surface area of the host. When exposed (1) singly in an equal
      water volume or, (2) simultaneously in the same tank, no differences in recovery
      of metacercariae per fish were found between "small" and "large" hosts. The
      latter observation is valid for three water volumes tested using the same number
      of cercariae per host. No significant difference in metacercarial infection was
      revealed in similar sized fish exposed at different host densities. It appears
      that transmission is more influenced by cercarial density (number of cercariae
      per water volume) and fish size than by fish density. These experimental findings
      support the view that cercarial infection of fish occurs by chance, presumably
      mainly in the gill region. Accordingly, in the field, individual fish size and
      cercarial density rather than fish population density, prevail in parasite
      transmission from snail to fish. This is of interest in coastal areas heated by
      cooling water, where fish growth and fish population density are enhanced.

PMID- 9599428
TI  - Pseudocapillaria yucatanensis sp. n. (Nematoda: Capillariidae) from the bagre
      Rhamdia guatemalensis (Pisces) from cenotes in Yucatan, Mexico.
AB  - A new nematode species, Pseudocapillaria yucatanensis sp. n., is described from
      the intestine of the freshwater pimelodid catfish Rhamdia guatemalensis (Gunther)
      from cenotes (= sinkholes) in Yucatan, Mexico. It differs from other three
      related species parasitizing freshwater fishes mainly in possessing the spicule
      with a simple rim of its proximal end and a non-expanded distal end, in the
      length of the spicule (0.218-0.295 mm), and the size (0.050-0.060 x 0.025-0.030
      mm), shape and structure of eggs, and also in the host types and geographical
      distribution. Pseudocapillaria yucatanensis is the first known autochtonous
      species of Pseudocapillaria parasitizing freshwater fishes in Mexico.

PMID- 9599429
TI  - Capillaria (Hepatocapillaria) cichlasomae (Nematoda: Capillariidae) from the
      liver of the cichlid fish Cichlasoma urophthalmus from Yucatan, Mexico.
AB  - Capillaria (Hepatocapillaria) cichlasomae sp. n., parasitic in the liver of the
      cichlid Cichlasoma urophthalmus (Gunther) from a small freshwater lake ("aguada")
      Xpoc in Yucatan, Mexico, is described. The parasite is characterized mainly by
      its small body size (male 1.8 mm, female 4.5 mm), the structure of the stichosome
      (markedly short stichocytes in one row) and the male (the presence of a pair of
      small subventral postanal papillae) and female (anus distinctly subterminal)
      caudal ends, and by the size and structure of the spicule (spicule 0.068-0.085 mm
      long, with marked transverse grooves on surface) and eggs (size 0.053-0.058 x
      0.023 mm, with protruding polar plugs). This is the second known Capillaria
      species from the liver of fish and the first one from the liver of a freshwater
      fish.

PMID- 9599430
TI  - Parenteral infection in mice with Baylisascaris transfuga (Nematoda: Ascaridae)
      infective eggs.
AB  - In order to investigate the ability of infective larvae of the nematode
      Baylisascaris transfuga (Rudolphi, 1819) Sprent, 1968 to hatch from the egg
      shells and then to migrate in tissues, parenteral infections of mice with
      embryonated eggs were performed. Two groups of outbred albino mice were infected
      with approximately 3500 B. transfuga infective eggs subcutaneously (s.c.) or
      intraperitoneally (i.p.). B. transfuga larvae in the i.p. group rapidly hatched
      and migrated to the intestine, liver, lungs, brain and carcass. Subcutaneous
      inoculation of eggs was followed also by migration of hatched larvae in the
      examined organs. In the s.c. mice, extensive encapsulating reactions involving
      the subcutaneous tissues and carcass, and containing large numbers of hatched
      eggs and free motile larvae, were found at the sites of inoculation. Some
      differences in the migratory behaviour were observed between the two groups. It
      is shown that B. transfuga infective larvae are able to hatch and migrate in
      tissues of mice, and tend to settle and/or to be trapped in the intestinal wall
      and muscles, even after parenteral inoculations of embryonated eggs. These
      results could provide basic data for further investigations on the migratory
      pathways of B. transfuga larvae or to perform immunological and therapeutical
      studies.

PMID- 9599431
TI  - Seasonal variation in the role of grey squirrels as hosts of Ixodes ricinus, the
      tick vector of the Lyme disease spirochaete, in a British woodland.
AB  - Data are presented on the variable patterns of the seasonal dynamics of Ixodes
      ricinus L. ticks seen questing on the vegetation and feeding on small rodents
      (mice and voles) and squirrels within a British woodland focus of Lyme
      borreliosis. Information on tick infestation levels on pheasants is also
      presented. The results show a prolonged, unimodal pattern of tick activity, with
      ticks feeding throughout the year in this sheltered habitat. If host density is
      taken into account, squirrels are quantitatively more important than small
      mammals as hosts for larval ticks from April until July, and overwhelmingly so
      for nymphal ticks throughout the year. The observed inter- and intraspecific
      differences in tick infestation levels are related to the behaviour of both hosts
      and ticks. Squirrels, as competent hosts for Borrelia burgdorferi and frequent
      occupants of habitats closely associated with man, will contribute significantly
      to the risk of Lyme disease.

PMID- 9599432
TI  - Determination of ubiquinone-9 and 10 levels in rat tissues and blood by high
      performance liquid chromatography with ultraviolet detection.
AB  - A high-performance liquid chromatographic (HPLC) method is presented for the
      simultaneous detection of ubiquinone-9 and 10 in rat tissues such as blood,
      myocardium, and muscle. After liquid-liquid extraction, the ubiquinones are
      subsequently analyzed by HPLC with ultraviolet (UV) detection at their maximum
      absorbance (275 nm). Reference calibration curves in ethanol are used to
      determine tissular levels of ubiquinones. Because a treatment with HMG-CoA
      reductase inhibitors is expected to decrease the ubiquinone levels, reference
      calibration curves are performed to ensure that the ratios (ubiquinone/internal
      standard) observed in such an experiment could be evaluated directly on a
      calibration curve. The assay is sensitive (0.0625 microgram/mL), reproducible (4%
      coefficient of variation for ubiquinone-9 and 6% for ubiquinone-10), and linear
      up to 20 micrograms/mL (or 100 mg of tissue) for ubiquinone-9 and up to 10
      micrograms/mL (or 100 mg of tissue) for ubiquinone-10. The ubiquinone levels in
      control tissues or blood are within the ranges of those previously reported.

PMID- 9599433
TI  - Analysis of dissolved methane, ethane, and ethylene in ground water by a standard
      gas chromatographic technique.
AB  - The measurement of dissolved gases such as methane, ethane, and ethylene in
      ground water is important in determining whether intrinsic bioremediation is
      occurring in a fuel- or solvent-contaminated aquifer. A simple procedure is
      described for the collection and subsequent analysis of ground water samples for
      these analytes. A helium headspace is generated above a water-filled bottle.
      Gases that are dissolved in the water partition between the gas and liquid phases
      and equilibrate rapidly. An aliquot of this headspace is analyzed by gas
      chromatography to determine the gases concentration in this phase. The
      concentration of the gas dissolved in the water can then be calculated based on
      its partitioning properties, as indicated by its Henry's Law constant.

PMID- 9599434
TI  - A simple ultraviolet method for discriminating between polychlorobiphenyls and
      organochloride pesticides coeluting under gas chromatography with electron
      capture detection.
AB  - Certain congeners of Aroclor 1260 coelute with o,p'-or p,p'-DDT under gas
      chromatography with electron-capture detection. We describe a simple ultraviolet
      irradiation method that allows qualitative and quantitative analyses of mixtures
      of these organochlorides in complex matrices. Detection limits are 0.20 and 0.22
      microgram/kg dry mass for Aroclor 1260 and the two DDTs, respectively. The method
      is applied to six replicate pork liver samples, for which recoveries ranged from
      72 to 90%.

PMID- 9599435
TI  - Depressives' future-event schemas and the social inference process.
AB  - Two studies examined depressed and nondepressed perceivers' characterizations and
      thoughtful inferences about the behaviors of another person. In Study 1,
      depressed and nondepressed participants under a cognitive load or no load were
      asked to make either dispositional (ability) or situational (task ease)
      inferences about a target's videotaped performance. When cognitive resources were
      limited, depressed compared with nondepressed individuals made more pessimistic
      characterizations. No depression-related differences were found when sufficient
      cognitive resources were available for inferential correction. Study 2 provided
      evidence that the depressed-nondepressed differences in characterizations could
      be accounted for by schema-based future-event expectancies (S. M. Andersen, L. A.
      Spielman, & J. A. Bargh, 1992). Results are examined in light of previous
      failures to find consistent differences as a function of level of depression in
      inferences about others.

PMID- 9599436
TI  - Getting "stuck" in the past: temporal orientation and coping with trauma.
AB  - The relations between temporal orientation and long-term psychological distress
      were studied cross-sectionally and longitudinally in 3 samples of traumatized
      individuals: adult victims of childhood incest, Vietnam War veterans, and
      residents of 2 southern California communities devastated by fire. Results
      indicated that a past temporal orientation--focusing attention on prior life
      experiences--was associated with elevated levels of distress long after the
      trauma had passed, even when controlling for the degree of rumination reported.
      Temporal disintegration at the time of the trauma--whereby the present moment
      becomes isolated from the continuity of past and future time--was associated with
      a high degree of past temporal orientation over time and subsequent distress.
      Temporal disintegration was highest among individuals who had experienced the
      most severe loss, had previously experienced chronic trauma, and had had their
      identities threatened by their traumatic experience.

PMID- 9599437
TI  - Reasoned action and social reaction: willingness and intention as independent
      predictors of health risk.
AB  - Three studies are described that assess elements of a new model of adolescent
      health-risk behavior, the prototype/willingness (P/W) model (F. X. Gibbons & M.
      Gerrard, 1995, 1997). The 1st analysis examined whether a central element of the
      prototype model, behavioral willingness, adds significantly to behavioral
      expectation in predicting adolescents' smoking behavior. The 2nd set of analyses
      used structural-equation-modeling procedures to provide the 1st test of the
      complete model in predicting college students' pregnancy-risk behavior. Finally,
      the 3rd study used confirmatory factor analysis to assess the independence of
      elements of the model from similar elements in other health behavior models.
      Results of the 3 studies provided support for the prototype model and, in
      particular, for 2 of its primary contentions: (a) that much adolescent health
      risk behavior is not planned and (b) that willingness and intention are related
      but independent constructs, each of which can be an antecedent to risk behavior.

PMID- 9599438
TI  - Paradoxical self-esteem and selectivity in the processing of social information.
AB  - Paradoxical self-esteem is defined as contrasting levels of self-liking and self
      competence. Consideration of the social and motivational implications of this
      uncommon form of self-esteem suggests that heightened selectivity in the
      processing of social information may be behind its persistence. Two experiments
      were conducted to confirm the prediction of heightened selectivity in
      paradoxicals. As expected, those paradoxically low in self-liking were more
      negatively biased in their memory for personality feedback (Study 1) and
      interpretation of valuatively ambiguous phrases (Study 2) than were their
      counterparts who shared the same low self-liking but were also low in self
      competence. Symmetrical with this result, those paradoxically high in self-liking
      exhibited a heightened positive bias relative to those who were high in both self
      liking and self-competence. The findings are discussed in relation to attitudes
      and motivation.

PMID- 9599439
TI  - Interpersonal and intrapsychic adaptiveness of trait self-enhancement: a mixed
      blessing?
AB  - Reactions to trait self-enhancers were investigated in 2 longitudinal studies of
      person perception in discussion groups. Groups of 4-6 participants met 7 times
      for 20 min. After Meetings 1 and 7, group members rated their perceptions of one
      another. In Study 1, trait self-enhancement was indexed by measures of narcissism
      and self-deceptive enhancement. At the first meeting, self-enhancers made
      positive impressions. They were seen as agreeable, well adjusted, and competent.
      After 7 weeks, however, they were rated negatively and gave self-evaluations
      discrepant with peer evaluations they received. In Study 2, an independent sample
      of observers (close acquaintances) enabled a pretest index of discrepancy self
      enhancement: It predicted the same deteriorating pattern of interpersonal
      perceptions as the other three trait measures. Nonetheless, all self-enhancement
      measures correlated positively with self-esteem.

PMID- 9599440
TI  - Intimacy as an interpersonal process: the importance of self-disclosure, partner
      disclosure, and perceived partner responsiveness in interpersonal exchanges.
AB  - H. T. Reis and P. Shaver's (1988) interpersonal process model of intimacy
      suggests that both self-disclosure and partner responsiveness contribute to the
      experience of intimacy in interactions. Two studies tested this model using an
      event-contingent diary methodology in which participants provided information
      immediately after their social interactions over 1 (Study 1) or 2 (Study 2)
      weeks. For each interaction, participants reported on their self-disclosures,
      partner disclosures, perceived partner responsiveness, and degree of intimacy
      experienced in the interaction. Overall, the findings strongly supported the
      conceptualization of intimacy as a combination of self-disclosure and partner
      disclosure at the level of individual interactions with partner responsiveness as
      a partial mediator in this process. Additionally, in Study 2, self-disclosure of
      emotion emerged as a more important predictor of intimacy than did self
      disclosure of facts and information.

PMID- 9599441
TI  - Ego depletion: is the active self a limited resource?
AB  - Choice, active response, self-regulation, and other volition may all draw on a
      common inner resource. In Experiment 1, people who forced themselves to eat
      radishes instead of tempting chocolates subsequently quit faster on unsolvable
      puzzles than people who had not had to exert self-control over eating. In
      Experiment 2, making a meaningful personal choice to perform attitude-relevant
      behavior caused a similar decrement in persistence. In Experiment 3, suppressing
      emotion led to a subsequent drop in performance of solvable anagrams. In
      Experiment 4, an initial task requiring high self-regulation made people more
      passive (i.e., more prone to favor the passive-response option). These results
      suggest that the self's capacity for active volition is limited and that a range
      of seemingly different, unrelated acts share a common resource.

PMID- 9599442
TI  - Temperament, activity, and expectations for later personality development.
AB  - Temperament is assumed to be the biologically based, emotional core of
      personality. Adult personality is presumed to emerge developmentally from
      temperament. One mechanism that may link temperament to subsequent personality
      development involves caregiver expectancies. Stability in personality may be
      associated with caregiver expectancies about the meaning of temperament-based
      behavior. The expectancies, in combination with implicit theories of personality
      development, support stability and patterned change. This multimethod study
      examined the relations among motor activity differences, temperament, and
      expectations about future personality characteristics in preschool children. It
      was hypothesized that motor activity and temperament differences would be linked
      to teachers' expectations about later personality development. The hypothesis
      that expectations about such links would be moderated by the sex of the child was
      also examined. Outcomes generally corroborated hypotheses. Results are discussed
      in terms of personality development and age-related adaptations to social
      contexts.

PMID- 9599443
TI  - Childhood personality influences on social-cognitive development: a longitudinal
      study.
AB  - The relation of childhood personality to the development of friendship
      understanding and moral judgment in adolescence was considered in a longitudinal
      study. Personality at age 7, assessed with the California Child Q-Set, was
      characterized in terms of ego-resiliency and ego-control. IQ and social class
      were also measured. Friendship understanding was assessed when the participants
      were ages 7, 9, 12, 15, and 19, and moral judgment was elicited when the
      participants were 12, 15, and 19. Ego-resiliency was found to predict social
      cognitive development in adolescence, even after the effects of IQ and childhood
      measures of social-cognitive development were controlled for. Analyses indicate
      that the effects of ego-resiliency on social-cognitive development are largely
      unmediated by the ability to focus attention or by social participation.

PMID- 9599444
TI  - Calibrating the sociometer: the relationship between interpersonal appraisals and
      state self-esteem.
AB  - Four experiments examined the functional relationship between interpersonal
      appraisal and subjective feelings about oneself. Participants imagined receiving
      one of several positive or negative reactions from another person (Experiments 1,
      2, and 3) or actually received interpersonal evaluations (Experiment 4), then
      completed measures relevant to state self-esteem. All 4 studies showed that
      subjective feelings were a curvilinear, ogival function of others' appraisals.
      Although trait self-esteem correlated with state reactions as a main effect, it
      did not moderate participants' reactions to interpersonal feedback.

PMID- 9599445
TI  - Anger and frontal brain activity: EEG asymmetry consistent with approach
      motivation despite negative affective valence.
AB  - The anterior regions of the left and right cerebral hemispheres have been posited
      to be specialized for expression and experience of approach and withdrawal
      processes, respectively. Much of the evidence supporting this hypothesis has been
      obtained by use of the anterior asymmetry in electroencephalographic alpha
      activity. In most of this research, however, motivational direction has been
      confounded with affective valence such that, for instance, approach motivation
      relates positively with positive affect. In the present research, we tested the
      hypothesis that dispositional anger, an approach-related motivational tendency
      with negative valence, would be associated with greater left- than right-anterior
      activity. Results supported the hypothesis, suggesting that the anterior
      asymmetry varies as a function of motivational direction rather than affective
      valence.

PMID- 9599446
TI  - Youthful precursors of midlife social support.
AB  - Measures of family stability, sociocultural background, and emotional ties to
      parents in medical students (N = 589, mean age = 22 years) predicted their social
      support measures, assessed 23 to 39 years later (mean age = 56 years). Father's
      education and family's involvement in church were positively associated with
      group participation (number of group memberships), whereas parental loss between
      the ages of 11 and 20 was negatively associated with group participation;
      perceived emotional closeness to parents was positively associated with social
      closeness (number of close contacts providing emotional and instrumental
      support). Thus, group participation and social closeness were influenced by
      distinctly different childhood factors.

PMID- 9599447
TI  - Do people know how they behave? Self-reported act frequencies compared with on
      line codings by observers.
AB  - Behavioral acts constitute the building blocks of interpersonal perception and
      the basis for inferences about personality traits. How reliably can observers
      code the acts individuals perform in a specific situation? How valid are
      retrospective self-reports of these acts? Participants interacted in a group
      discussion task and then reported their act frequencies, which were later coded
      by observers from videotapes. For each act, observer-observer agreement, self
      observer agreement, and self-enhancement bias were examined. Findings show that
      (a) agreement varied greatly across acts; (b) much of this variation was
      predictable from properties of the acts (observability, base rate, desirability,
      Big Five domain); (c) on average, self-reports were positively distorted; and (d)
      this was particularly true for narcissistic individuals. Discussion focuses on
      implications for research on acts, traits, social perception, and the act
      frequency approach.

PMID- 9599448
TI  - The persistent use of negative affect by anxious individuals to estimate risk.
AB  - Three experiments investigated how trait anxiety would influence individuals'
      assumptions about the relevance of their experiences of state anxiety for
      judgments of risk. Experiment 1 found that attributions of state anxiety to a
      judgment-irrelevant source reduced the risk estimates of low, but not of high,
      trait-anxious individuals. The results of Experiment 2 suggest that attribution
      manipulations reduce the influence of state affect on judgment only when the
      state affect is inconsistent with participants' trait affect. Experiment 3
      revealed that these effects can be controlled by explicitly manipulating
      participants' assumptions about the relevance of their feelings. Regardless of
      the level of trait anxiety, attributions were effective at reducing mood effects
      when facts, but not feelings, were assumed to be the relevant basis for judgment.
      Overall, the results suggest that trait-consistent affect is more readily assumed
      to be informative and hence is more likely to be relied on than trait
      inconsistent affect.

PMID- 9599449
TI  - Schemas, sexuality, and romantic attachment.
AB  - One's self-views are powerful regulators of both cognitive processing and
      behavioral responding. Sexual self-schemas are cognitive generalizations about
      sexual aspects of the self. The bivariate sexual self-schema model, which posits
      independent effects of positive and negative components of women's sexual self
      views, was tested. Three hundred eighteen female undergraduates completed
      anonymous questionnaires, including the Sexual Self-Schema Scale and assessments
      of sexual responses and romantic attachment patterns. Results extended knowledge
      of positive-negative schema group contrasts and distinguished the response
      patterns of the aschematic and co-schematic groups. As predicted, aschematics
      reported low levels of sexual desire, arousal, and anxiety, and weak romantic
      attachments, whereas co-schematics endorsed conflicting positive and negative
      responses to sexual-romantic cues. In addition, path analyses supported the
      bivariate model. Finally, findings are related to theories of attachment
      representations within the cognitive hierarchy of the self.

PMID- 9599450
TI  - Attachment styles, emotion regulation, and adjustment in adolescence.
AB  - Attachment style differences in psychological symptomatology, self-concept, and
      risky or problem behaviors were examined in a community sample (N = 1,989) of
      Black and White adolescents, 13 to 19 years old. Overall, secure adolescents were
      the best-adjusted group, though not necessarily the least likely to engage in
      risky behaviors. Anxious adolescents were the worst-adjusted group, reporting the
      poorest self-concepts and the highest levels of symptomatology and risk
      behaviors. In contrast, avoidant adolescents reported generally high levels of
      symptomatology and poor self-concepts but similar levels of risk behaviors to
      those found among secures. Mediation analyses suggested that the observed
      differences in problem behaviors were at least partially accounted for by the
      differential experience of distress symptoms (primarily hostility and depression)
      and by social competence. Finally, patterns of attachment effects were similar
      across age, gender, and racial groups, with some important exceptions.

PMID- 9599452
TI  - Some logical functions of joint control.
AB  - Constructing a behavioral account of the language-related performances that
      characterize responding to logical and symbolic relations between stimuli is
      commonly viewed as a problem for the area of stimulus control. In response to
      this problem, the notion of joint control is presented here, and its ability to
      provide an interpretative account of these kinds of performances is explored.
      Joint control occurs when the currently rehearsed topography of a verbal operant,
      as evoked by one stimulus, is simultaneously evoked by another stimulus. This
      event, the onset of joint stimulus control by two stimuli over a common response
      topography, then sets the occasion for a response appropriate to this special
      relation between the stimuli. Although the mechanism described is simple, it
      seems to have broad explanatory properties. In what follows, these properties are
      applied to provide a behavioral interpretation of two sorts of fundamental,
      putatively cognitive, performances: those based on logical relations and those
      based on semantic relations. The first includes responding to generalized
      conceptual relations such as identity, order, relative size, distance, and
      orientation. The second includes responding to relations usually ascribed to word
      meaning. These include relations between words and objects, the specification of
      objects by words, name-object bidirectionality, and the recognition of objects
      from their description. Finally, as a preview of some further possibilities, the
      role of joint control in goal-oriented behavior is considered briefly.

PMID- 9599451
TI  - Food-deprivation level alters the effects of morphine on pigeons' key pecking.
AB  - Four pigeons pecked response keys under a multiple fixed-ratio 30 fixed-interval
      5-min schedule of food presentation. Components alternated separated by 15-s
      timeouts; each was presented six times. Pigeons were maintained at 70%, 85%, and
      greater than 90% of their free-feeding weights across experimental conditions.
      When response rates were stable, the effects of morphine (0.56 to 10.0 mg/kg) and
      saline were investigated. Morphine reduced response rates in a dose-dependent
      manner under the fixed-ratio schedule and at high doses under the fixed-interval
      schedule. In some cases, low doses of morphine increased rates under the fixed
      interval schedule. When pigeons were less food deprived, reductions in pecking
      rates occurred at lower doses under both schedules for 3 of 4 birds compared to
      when they were more food deprived. When pigeons were more food deprived, low
      doses of morphine increased rates of pecking in the initial portions of fixed
      intervals by a greater magnitude. Thus, food-deprivation levels altered both the
      rate-decreasing and rate-increasing effects of morphine. These effects may share
      a common mechanism with increased locomotor activity produced by drugs and with
      increased drug self-administration under conditions of more severe food
      deprivation.

PMID- 9599453
TI  - Mutagenicity and amount of chloroform after chlorination of bank filtered lake
      water.
AB  - Chlorinated drinking waters produced from humus-rich waters often have a high
      content of halogenated organic by-products which increases the mutagenicity of
      drinking water. With in vitro chlorination experiments we studied the formation
      of chloroform (CHCl3) and mutagenicity of artificially recharged ground water
      samples. The water samples where obtained from an artificial ground water plant
      which infiltrates humus-rich lake water through an esker island. The chlorination
      experiments showed that bank filtration reduced strongly the formation of
      chloroform and mutagenicity of chlorinated water. Reduction in the amount of
      chloroform and mutagenicity in chlorinated waters was strongly associated with
      the decrease in the total content of organic carbon and with the decrease in
      molecular weight of organic matter during bank filtration.

PMID- 9599454
TI  - Organochlorine pesticides and polychlorinated biphenyls in human milk of mothers
      living in northern Germany: current extent of contamination, time trend from 1986
      to 1997 and factors that influence the levels of contamination.
AB  - This study reports the concentration levels of PCB, DDT, HCB and beta-HCH in the
      human milk of women living in northern Germany over a period of 12 years and
      determines factors that may influence these levels. From 1986 to 1997 more than
      3500 milk samples were analyzed for organochlorine compounds. A questionnaire was
      used to obtain information regarding personal characteristics, life style factors
      and eating habits. Descriptive statistics of concentration levels were computed
      to characterize the current extent of contamination. To follow time trends across
      the years homogeneous subgroups were compared and multiple regression analyses
      were used to investigate associations between determining factors and specific
      contaminants. Between summer 1995 and summer 1997 the median PCB concentration
      level was 0.502 mg/kg, the median DDT level 0.202 mg/kg, the median HCB level
      0.065 mg/kg and the median beta-HCH level 0.036 mg/kg, all values expressed on a
      fat basis. The median concentration levels decreased by 80-90% during the past 12
      years and the median PCB levels by 60%. The concentration levels of all
      substances were positively correlated with maternal age and negatively associated
      to parity, to the total period of breast-feeding and to a weight increase of
      mothers before and after delivery. Post-pregnancy BMI was a significant predictor
      of the likelihood of having higher concentrations for DDT, HCB and beta-HCH and
      of having lower concentrations for PCB levels. A balanced diet for at least 3
      years was related to lower HCB and beta-HCH levels. Women who ate more than 100 g
      of fish or more than 700 g of meat per week were more likely to have higher PCB
      and beta-HCH levels or higher HCB levels, respectively. Higher HCB and beta-HCH
      concentration levels were associated with lower birth weights of female infants.

PMID- 9599455
TI  - Mutagenic activities of exhaust gas and ash from sludge incineration plants.
AB  - We have found that the exhaust gas from many incineration plants of municipal
      solid wastes (MSW) show significant mutagenic activities. The mutagenic
      activities of exhaust gas from incineration plants of the other wastes have not
      been studied in detail. Here, we analyzed the mutagenic activities and compounds
      in exhaust gas and ash from seven sludge incineration plants. Some samples of the
      exhaust gas from the sludge incineration plants showed high mutagenic activities;
      although, none of the ash residues showed mutagenic activities. There was no
      relationship between the mutagenic activities and furnace types, the plant size
      or the apparent residence time of the gas in the furnace. The mutagenic
      activities of the exhaust gas were produced during incomplete combustion at lower
      temperatures. Direct mutagenic activities without S9 mix were higher than
      indirect mutagenic activities with S9 mix which was made from rat liver
      homogenate and was used to test mutagenic activity after metabolism. These
      results are different to those of MSW incineration plants. We analyzed the
      mutagenic compounds in the exhaust gas by GC/MS after fractionation by HPLC, but
      they could not be identified. We found that the mutagenic compounds in the
      exhaust gas were different from the compounds that were produced from the MSW
      incineration plants. We believed that these mutagenic compounds might be non
      volatile and more polar than the heterocyclic amines, Trp-P-2, Trp-P-1 and Glu-P
      1, which are typical mutagenic compounds in sewage and sludge.

PMID- 9599456
TI  - A dynamic flux chamber to measure mercury emission from aquatic systems.
AB  - A floating flux chamber, built of Plexiglas, has been developed to measure vapour
      phase mercury fluxes over aquatic systems. The chamber is connected via Teflon
      tubes to a semi-automatic sampling device and to a mercury analyzer (battery
      powered) to perform the determination of mercury emission in situ. Relatively low
      chamber blanks have been observed both in laboratory and in field conditions. The
      low detection limit of the analyzer (0.5 pg of mercury) allows measurements of
      mercury concentration in a short period of time (10 min). In this way it is
      possible to follow the real-time temporal trend of mercury emission. Some data
      obtained with this flux chamber in selected areas of the Mediterranean basin are
      reported.

PMID- 9599457
TI  - Concentrations and spatial variations of cyclodienes and other organochlorines in
      herring and perch from the Baltic Sea.
AB  - Herring (Clupea harengus) and perch (Perca fluviatilis) were collected in the
      northern and southern Baltic Sea and analyzed for the presence of the cyclodiene
      pesticides chlordane (CHL), heptachlor, aldrin, dieldrin, endrin, isodrin,
      endosulfan and mirex, as well as other organochlorine contaminants,
      hexachlorocyclohexanes (HCHs), DDTs, hexachlorobenzene (HCBz) and polychlorinated
      biphenyls (PCBs) in order to investigate concentrations, accumulation and
      differences in geographical distribution. In the northern part of the Baltic Sea,
      Gulf of Bothnia, herring were collected at two pelagic stations, one in the
      Bothnian Bay (BB) and the other in the Bothnian Sea (BS), respectively; perch
      were collected at four coastal locations along the Swedish coast. All these
      locations were selected to represent background areas except one in the vicinity
      of an industrialised and contaminated area. Both specimens were also caught in
      the southern part of the Baltic Sea, in the Gulf of Gdansk (GG), Poland, a
      potentially highly polluted area. From the eight cyclodiene pesticides analyzed,
      three were detected in herring and perch samples, including 12 different CHL
      related compounds, dieldrin and mirex. To our knowledge, it is the first time
      that mirex has been detected in samples from the Baltic Sea. Neither heptachlor,
      aldrin, endrin, isodrin nor endosulfan were found. However, HCHs, DDTs, HCBz and
      PCBs were found in every sample investigated, and the concentrations ranged e.g.
      for the cyclodiene chemicals dieldrin and CHL-related compounds from 30 to 170
      ng/g lipid and for PCBs from 360 to 5400 ng/g lipid, both fish species included.
      Differences in contamination burden between the sites can be seen, e.g. for
      herring the BB and GG locals were similar, and generally lower than BS for all
      chemicals except that of DDT where GG was the highest. For the perch samples the
      industrialised location had markedly higher concentrations of HCBz and PCBs than
      the other locations. This species also identifies GG as the most DDT contaminated
      site among the three studied areas.

PMID- 9599458
TI  - Risk in cleaning: chemical and physical exposure.
AB  - Cleaning is a large enterprise involving a large fraction of the workforce
      worldwide. A broad spectrum of cleaning agents has been developed to facilitate
      dust and dirt removal, for disinfection and surface maintenance. The cleaning
      agents are used in large quantities throughout the world. Although a complex
      pattern of exposure to cleaning agents and resulting health problems, such as
      allergies and asthma, are reported among cleaners, only a few surveys of this
      type of product have been performed. This paper gives a broad introduction to
      cleaning agents and the impact of cleaning on cleaners, occupants of indoor
      environments, and the quality of cleaning. Cleaning agents are usually grouped
      into different product categories according to their technical functions and the
      purpose of their use (e.g. disinfectants and surface care products). The paper
      also indicates the adverse health and comfort effects associated with the use of
      these agents in connection with the cleaning process. The paper identifies
      disinfectants as the most hazardous group of cleaning agents. Cleaning agents
      contain evaporative and non-evaporative substances. The major toxicologically
      significant constituents of the former are volatile organic compounds (VOCs),
      defined as substances with boiling points in the range of 0 degree C to about 400
      degrees C. Although laboratory emission testing has shown many VOCs with quite
      different time-concentration profiles, few field studies have been carried out
      measuring the exposure of cleaners. However, both field studies and emission
      testing indicate that the use of cleaning agents results in a temporal increase
      in the overall VOC level. This increase may occur during the cleaning process and
      thus it can enhance the probability of increased short-term exposure of the
      cleaners. However, the increased levels can also be present after the cleaning
      and result in an overall increased VOC level that can possibly affect the indoor
      air quality (IAQ) perceived by occupants. The variety and duration of the
      emissions depend inter alia on the use of fragrances and high boiling VOCs. Some
      building materials appear to increase their VOC emission through wet cleaning and
      thus may affect the IAQ. Particles and dirt contain a great variety of both
      volatile and non-volatile substances, including allergens. While the volatile
      fraction can consist of more than 200 different VOCs including formaldehyde, the
      non-volatile fraction can contain considerable amounts (> 0.5%) of fatty acid
      salts and tensides (e.g. linear alkyl benzene sulphonates). The level of these
      substances can be high immediately after the cleaning process, but few studies
      have been conducted concerning this problem. The substances partly originate from
      the use of cleaning agents. Both types are suspected to be airway irritants.
      Cleaning activities generate dust, mostly by resuspension, but other occupant
      activities may also resuspend dust over longer periods of time. Personal sampling
      of VOCs and airborne dust gives higher results than stationary sampling.
      International bodies have proposed air sampling strategies. A variety of field
      sampling techniques for VOC and surface particle sampling is listed.

PMID- 9599459
TI  - Non-occupational exposure of adult women in Manila, the Philippines, to lead and
      cadmium.
AB  - In total, 45 adult women in Manila, the Philippines, volunteered to participate
      in the study by offering peripheral blood samples and 24-h total food duplicate
      samples. In addition, they offered raw (uncooked) rice as well as wheat flour and
      maize starch from the kitchen. Lead (Pb) and cadmium (Cd) in food duplicates and
      blood samples were measured by inductively coupled plasma mass spectrometry after
      homogenization (when necessary) and wet-ashing. The consumption of rice, wheat
      and maize was calculated by weighing each food item in the duplicates taking
      advantage of the food composition tables. The dietary exposure level of the women
      was 11 micrograms Pb/day and 14 micrograms Cd/day, and the levels of Pb and Cd in
      their blood were 37 ng Pb/ml and 0.47 ng Cd/ml. There is a subtle age-dependent
      increase in the dietary burden of Pb and Cd and also in blood levels of Pb and
      Cd. Rice accounted for 18 and 21% of dietary Pb and Cd intake, respectively and
      cereals (i.e. rice, wheat and maize in combination) accounted for 24% both for Pb
      and Cd. The calculation from the published data on air quality in Manila
      suggested that another and yet a greater source of Pb burden was Pb in
      atmospheric air which may account for 85% of total Pb uptake, whereas the amount
      of Cd in air was quite small (i.e. < 10% of the total uptake).

PMID- 9599460
TI  - The Swedish HIV epidemics seen in the rear view: small "nuclear groups" are
      responsible for the transmission in the country.

PMID- 9599461
TI  - [Strong connection between papillomavirus and cervix cancer. More precise
      cytology is needed, cancer transformation may occur rapidly].

PMID- 9599462
TI  - [Damaged cell organelle in spermatozoa prevents fetal development].

PMID- 9599463
TI  - [A controversial research project. Transplantation of seminal stem cells to mice
      will help infertile males].

PMID- 9599464
TI  - [The regions should be basis for the system of continuing education!].

PMID- 9599465
TI  - [The SFOG prioritizes continuing education. The CME is introduced!].

PMID- 9599466
TI  - [Obligatory referrals--yes, please!].

PMID- 9599467
TI  - [Acupuncture complication or unskilled professional practice?].

PMID- 9599468
TI  - ["...to escape in the world of books?].

PMID- 9599469
TI  - [No patient consults emergency department without reason].

PMID- 9599470
TI  - [A renaissance for physical therapy in the treatment of cerebral palsy.
      Therapeutic methods in cerebral palsy].

PMID- 9599471
TI  - [All children with cerebral palsy are systematically followed-up. A project on
      cooperation between pediatric orthopedics and pediatric rehabilitation in
      Southern Sweden].

PMID- 9599472
TI  - [Children in a day care center that concentrates on outdoor activities are less
      frequently sick].

PMID- 9599473
TI  - [When Marcel Proust's grandmother died of stroke the famous Parisian professor
      Dieulafoy was there].

PMID- 9599474
TI  - [How to describe the status in acute abdomen? A unified Swedish nomenclature is
      proposed].

PMID- 9599475
TI  - [No "unnecessary" care when measured by American standards. The Oregon list
      tested at a department of otorhinolaryngology in Halmstad].
AB  - It is often asserted in the health care debate that stricter priority setting
      would be one way of solving some of the economic problems. However, comparison of
      the workload at a Swedish ENT department with the Oregon list, one of the
      strictest prioritisation instruments yet devised, suggests that this is not the
      case. After adaptation of the Oregon list to the norms of Swedish practice (e.g.,
      current policy regarding tonsillectomy, as elicited from Scandinavian studies),
      very little of the remaining workload would not be approved according to the
      Oregon list. Thus the scope for economy would appear to derive from professional
      skill in the internal planning of diagnostic investigation and treatment, rather
      than from the application of prioritisation systems devised by others.

PMID- 9599476
TI  - [A HIV epidemics threatens Asia].

PMID- 9599477
TI  - [HIV in Africa is transmitted with varying intensity].

PMID- 9599478
TI  - [A 2-year study of 77 dancers. Almost 90 per cent needed help because of injury].

PMID- 9599479
TI  - [New target groups for vaccination against hepatitis A: homosexual men, addicts
      and persons with chronic liver disease].

PMID- 9599480
TI  - [Skin reactions can be now measured exactly and objectively].

PMID- 9599481
TI  - [An American idyll of family practitioner].

PMID- 9599482
TI  - [An answer to Claes Ortendahl: how is the consent to be included in the new drug
      registry].

PMID- 9599483
TI  - [Patients with autism are offended in psychotherapy].

PMID- 9599484
TI  - [Sudden severe headache may be a warning of hemorrhage. Early discovery of
      aneurysm may improve the prognosis in subarachnoid hemorrhage].

PMID- 9599485
TI  - [First study of hepatitis occurence in Sweden: low immunity is associated with
      susceptibility to infection].

PMID- 9599487
TI  - [Prevention also should be evidence-based. Prevention and public health work
      within primary health care].

PMID- 9599486
TI  - [A new model for emergency internal medicine. Good quality of care in spite of
      shorter length of stay].

PMID- 9599488
TI  - [Medical students about sexual perspective].

PMID- 9599490
TI  - [Hope's "address" is not always a physician].

PMID- 9599491
TI  - [Biological warfare].

PMID- 9599489
TI  - [Different policy on gluten-free food in child day care centers. Unified national
      guidelines are needed].

PMID- 9599493
TI  - [Women, headache and stroke].

PMID- 9599492
TI  - [Honesty, honour and history writing].

PMID- 9599494
TI  - [Hearing aids--are they used?].

PMID- 9599495
TI  - [Snowmobile accidents--a special challenge to traffic medicine].

PMID- 9599496
TI  - [Local community, crises and mental health].

PMID- 9599497
TI  - [Mental health in costal areas of Finnmark 1987-93].
AB  - Over 70% of the adult population of five rural communities in Northern Norway
      participated in a three-part epidemiological study that included identical
      questions on mental health. Data were collected in 1987/88, 1990 and 1993. Both
      repeated cross-sectional analyses and individual growth curve analyses on the
      2,486 individuals who participated in either two or three surveys were carried
      out in order to reveal the changes in mental health over time. The proportion of
      the population using sleeping pills or psychotropic drugs decreased significantly
      as time progressed. There were also a significant decrease in the proportion of
      people who reported being depressed or dissatisfied with life, or who had
      insomnia or problems in coping. A similar improvement in mental health was noted
      for both sexes and it remained statistically significant even after adjusting for
      age and level of education. There was no decrease in the proportion of
      individuals who reported loneliness. The time effect remained significant, even
      after adjusting for multiple factors in the growth curve analyses. Improvement in
      mental health has occurred despite the crisis in the region's fishing industry.

PMID- 9599498
TI  - [Coronary heart diseases among Lapps and Norwegians in Finnmark].
AB  - The Finnmark Health Survey of 1987-88 showed that there was no significant
      difference in the prevalence of coronary heart disease between a Sami population
      and a Norwegian population. Among men 40-59 years of age, a prevalence of
      myocardial infarction or angina pectoris or both, of 5.5%, was found both in
      Norwegians and in the predominantly Sami population of Inner Finnmark. Among
      women, a prevalence of 3.1% and 3.3% was found among Norwegians and Samis,
      respectively. The difference in results between males and females was less among
      Samis than Norwegians, despite Sami women having a lower risk factor level than
      Norwegian women. A clinical follow-up study done in 1992-93 showed no significant
      differences in serum lipid concentrations between the Sami and the Norwegian
      population. Samis had a lower familial occurrence of coronary heart disease than
      Norwegians. Waist to hip ratio was higher among Samis than Norwegians.

PMID- 9599499
TI  - [Acupuncture in stroke].
AB  - In 1995 we reported that acupuncture treatment of stroke patients in the subacute
      stage resulted in added therapeutic benefit. The purpose of the present study was
      to determine, one year after discharge from the rehabilitation centre, whether
      the treatment continued to have effect. Initially, 45 stroke patients were
      included in the study; median 40 days post stroke. The patients were randomized
      into two groups; one acupuncture group and one control group, taking into
      considering the patients' sex and the actual site of the lesion. All subjects
      received an individually adapted, multidisciplinary rehabilitation programme. The
      acupuncture group received additional treatment with classical acupuncture for
      six weeks. The patients were thereafter given individual treatment at the
      rehabilitation centre and then under the primary health care service. 41 of the
      patients were available for further study one year after treatment ended; 21
      patients from the acupuncture group and 20 from the control group. The results
      show that there was a significantly greater improvement in the acupuncture group
      than in the control group, both during the six-week treatment period, and even
      more so during the following year. These assessments were based on the Motor
      Assessment Scale, the Sunnaas Index of Daily Living (ADL), the Nottingham Health
      Profile and the patients' social circumstances.

PMID- 9599501
TI  - [How old can one become?].
AB  - We recorded the highest age at the time of death for both men and women in Norway
      for the years 1970 to 1995. During this period longevity increased by
      approximately one year; for women from 106 to 107 years and for men from 105 to
      106 years. Based on Gumbel's theory, we have estimated the most probable highest
      age for the next 10, 20, and 100 years. For women this was found to be 109, 110
      and 113 years, respectively; for men the corresponding ages were 108, 109 and 112
      years. Our aim must be that as many men and women as possible live to a high age,
      that their latter years are meaningful, and that they enjoy a high standard of
      living.

PMID- 9599500
TI  - [Can acupuncture prevent cystitis in women?].
AB  - 67 adult women with a history of recurrent lower urinary tract infection (UTI)
      were randomized for acupuncture treatment, sham acupuncture, or no treatment. The
      incidence rate of UTI over the following six months was noted. In the acupuncture
      group a total of 85% was free of cystitis during the six-month observational
      period, as compared to 58% in the sham group (p < 0.05), and 36% in the control
      group (p < 0.01). Compared to the acupuncture group, twice as many incidents of
      cytitis occurred in the sham group, and three times as many in the control group
      (p < 0.05). Acupuncture seems a worthwhile alternative in the prevention of
      frequently recurring cystitis in women.

PMID- 9599502
TI  - [How are the retired physicians?].
AB  - As part of an extensive cross-sectional survey of Norwegian physicians carried
      out in 1993 the 1,158 retired members of The Norwegian Medical Association were
      sent a questionnaire about their social situation, work activity, health and well
      being. The response rate was 76%. 62% of the respondents were 75 years or older,
      and 13% were women. 44% were still active, doing clinical, research, or
      consultation work. The most prevalent complaint was lower back trouble, followed
      by arthrosis and hypertension. It was relatively common to prescribe one's own
      drugs. 6-8% of physicians under 75 years and 28% of those over 84 years needed
      practical help, but the great majority rated their life quality as good or
      excellent.

PMID- 9599503
TI  - [Sherlock Holmes as amateur physician].
AB  - The medical literature contains numerous articles dealing with Sherlock Holmes
      and his companion Dr. Watson. Some of the articles are concerned with the medical
      and scientific aspects of his cases. Other articles adopt a more philosophical
      view: They compare the methods of the master detective with those of the
      physician--the ideal clinician should be as astute in his profession as the
      detective must be in his. It this article the author briefly reviews the
      abilities of Sherlock Holmes as an amateur physician. Often Holmes was brilliant,
      but sometimes he made serious mistakes. In one of his cases (The Adventure of the
      Lion's Mane) he misinterpreted common medical signs.

PMID- 9599504
TI  - [Receptor mediated effects of adenosine and caffeine].
AB  - Adenosine consists of one ribose and one purine moiety and binds to specific
      receptors on cell membranes. The receptors are coupled to G-proteins and
      additionally to various effector-systems. When a mismatch occurs between energy
      supply and energy demand, adenosine is produced by the catabolism of adenosine
      triphosphate. The metabolism of an organ is thereby coupled to the local blood
      supply (metabolic vasodilation). In addition to vasodilation, adenosine has
      several electrophysiological, cardioprotective, metabolic, and antiinflammatory
      properties. Adenosine is rapidly metabolized in blood and interstitial fluid,
      through cell absorption and degradation by adenosine deaminase. The short half
      life of adenosine limits its clinical value. However, there are several ways of
      increasing the interstitial concentration of adenosine. At present, adenosine or
      adenosine-potentiating substances are used clinically to terminate
      supraventricular tachycardias, to induce myocardial ischemia in patients who are
      unable to exercise, and to reduce myocardial ischemia or reperfusion injury.
      Caffeine and other methylxanthines are adenosine receptor antagonists, and
      several of the pharmacodynamic properties of these substances are caused by
      adenosine receptor antagonism.

PMID- 9599505
TI  - [Cerebral microembolism detected by transcranial Doppler ultrasonography].
AB  - The clinical diagnosis of brain embolism has traditionally been based on evidence
      suggesting a potential embolic source. However, it is now possible to detect
      circulating cerebral microemboli by means of transcranial Doppler ultrasound. We
      explain the theory behind microembolus detection, and discuss initial clinical
      experience of this method. During invasive cardiovascular investigations and
      surgery this method can warn the physician that microemboli are entering the
      cerebral circulation, and preventive measures can be taken. Cerebral microemboli
      are quite often detected in stroke prone patients, and their presence probably
      indicates increased risk of stroke. In the acute phase of ischemic stroke,
      microembolus detection may help to decide the etiology and the source of the
      emboli. When microemboli are detected in cases of acute embolic stroke, serial
      detections can be performed which, in future studies, might be of help when
      evaluating the effect of the treatment.

PMID- 9599506
TI  - [Is headache a women's disease?].
AB  - Headache is experienced by the majority of people in the population. The
      prevalence of migraine in women is greater than in men, and there are indications
      that this is also the case for non-migrainous headache. We reviewed available
      literature on headache epidemiology for documented knowledge on the prevalence of
      non-migrainous headache in men and women and severity of the disease. In this
      article we present a summary of 13 studies of the general population where
      prevalence of the common headache in men and women could be expressed as a gender
      ratio. The studies covered the period 1977-96, and included a total number of
      75,000 people. The review confirms that non-migrainous headache is a women's
      disease, in that a female dominated gender ratio was found consistently
      throughout the studies. However, female dominance is not as great as for
      migraine. Varying definitions of headache resulted in a great variation in
      prevalence across the studies, but this did not influence the gender ratio. From
      the literature available no conclusions can be drawn on gender differences
      related to severity or frequency of the non-migrainous headache. These areas need
      to be explored further in order to provide adequate health care for men and women
      suffering from headache.

PMID- 9599507
TI  - [Migraine and stroke].
AB  - When young patients suffer a stroke the etiology often differs from that found in
      the elderly. One of the risk factors for stroke in young people could possibly be
      migraine. The first author to describe what was probably a migrainous cerebral
      infarction was Wepfer, in 1727. In recent years, cases of stroke in migraineurs
      have been frequently reported. Extensive cohort studies and smaller, well
      conducted case-control studies seem to confirm that migraine is a risk factor for
      stroke. However, the risk is only moderately increased, perhaps doubled. Among
      women under the age of 45, the correlation is greater with a threefold increased
      risk of stroke in a migraineur; it is even greater in patients suffering attacks
      of migraine with aura. Pure migrainous infarctions are probably rare and reports
      are perhaps exaggerated in the literature. Cerebral ischaemia may lead to
      symptomatic migraine attacks. Overall, the absolute risk of stroke is small
      enough to validate the opinion that migraine is a benign condition.

PMID- 9599508
TI  - [Hearing aids among the elderly--not only in the drawer!].
AB  - The majority of hearing-aids are offered to elderly patients with presbyacusis.
      It is commonly assumed in the general population and among health professionals
      that many hearing-aids are not being used regularly on a daily basis. 83 patients
      over the age of 70 were visited unannounced and interviewed in their homes. They
      had received their first or replacement hearing-aid from six months to two years
      earlier. The main purpose of the interview was to examine to what extent the
      hearing-aids were in regular use. Nearly half of the patients said they wore
      their hearing-aid when they opened the front door and that they used it
      constantly during the day. This was also confirmed by relatives. One of five
      stated that they did not use the hearing-aid at all, or that they were not able
      to find it. The majority of users were satisfied with their hearing-aid, and
      relatives found it to be of great help. Even patients over 80 years old managed
      to fit their hearing-aid themselves, regulate the volume and change the
      batteries. There was an even distribution of all-day users regardless of the
      extent of hearing loss. Whether the hearing-aid was prescribed on the initiative
      of a third party or not made little difference to the extent of its use. A
      significant difference was found between first-time users and those with a
      replacement hearing-aid, replacement hearing-aids being used much more
      frequently. We conclude that hearing-aids are indeed being used by the majority
      of elderly people with impaired hearing and that they are of great benefit to
      them. It is difficult to predict from the medical history and audiometric data of
      the individual patient exactly how much the hearing-aid will be used later and
      how beneficial it will be. Patients should therefore be allowed to test a hearing
      aid at home for a period of time and to return it if it is found to be of little
      benefit.

PMID- 9599509
TI  - [Physicians and the medical society--between the interests and values].

PMID- 9599511
TI  - [Handicap--also an etymological challenge].

PMID- 9599510
TI  - [Public health--health of the public?].

PMID- 9599512
TI  - [Transcendental meditation, autogenous training and hypertension].

PMID- 9599513
TI  - [Osteoporosis and gravitation].

PMID- 9599514
TI  - [Problem-based learning--a demanding task].

PMID- 9599515
TI  - [What happened to the confidence intervals?].

PMID- 9599516
TI  - [Why anti-gout agents when patients with gouty arthritis are to be surgically
      treated].

PMID- 9599517
TI  - [Antibiotic treatment in threatened preterm labor].

PMID- 9599518
TI  - [Reconstructive joint surgery and rheumatoid arthritis. Status over a developing
      field].
AB  - Rheumatoid arthritis has a prevalence of between 1% and 2%. The majority of
      patients face the prospect of surgical treatment of joints, that do not respond
      to medical treatment. With respect to the extensive development in joint surgery
      during the last decade, today's recommendations for surgical treatment of the
      individual joints are surveyed.

PMID- 9599519
TI  - [Risk factors for the development of asthma in children and adolescents. Results
      of a longitudinal study].
AB  - To investigate risk factors for the development of asthma, a population sample of
      children and adolescents, aged 7 to 17 yrs at enrollment, were studied twice,
      with a six year interval; complete data was available for 408 subjects (199
      males). Obtained case history was used to assess the presence of asthma;
      pulmonary function, skin prick test reactivity, total serum IgE and bronchial
      responsiveness to inhaled histamine (BHR) were measured using standard
      techniques. The 12-month period prevalence of asthma increased significantly from
      the first to the second examination in both males (p < 0.001) and females (p <
      0.001), whereas the number of subjects with a positive histamine challenge test
      declined in both sexes. The prevalence of a positive skin prick test was higher
      at the second examination (26% and 44%, respectively, p < 0.001); the proportion
      of subjects with a positive skin reaction to house dust mite (HDMpos) increased
      from 14% to 26%. Confining the analysis to subjects without a history of asthma
      at the first examination showed that asymptomatic BHR (Odds Ratio [OR] 3.8 [95%
      Confidence Interval (CI) 2.5-5.1], p = 0.0002), HDMpos (OR 2.6 [CI 1.9-3.3], p =
      0.005), a history of wheezy bronchitis before the age of two yrs (OR 3.8 [CI 2.4
      5.2], p = 0.006) and a history of rhinitis and/or eczema (OR 2.8 [CI 1.7-3.9], p
      = 0.007) at first examination were associated with an increased risk for
      development of symptomatic asthma at some point between the two examinations. No
      significant relationship could be demonstrated between smoking (passive or
      active) and the risk for development of asthmatic symptoms. In conclusion, this
      longitudinal population study showed an increase in the 12-month period
      prevalence of asthma with sensitization to HDM and asymptomatic BHR as important
      risk factors for development of asthma.

PMID- 9599520
TI  - [Peroral drug administration to children--are there any problems?].
AB  - Children's compliance with orally administered medicine is described. Five
      hundred questionnaires were given to the parents of children at their first visit
      at the out-patient clinic with a response from 484. Three hundred and ninety
      seven children had been treated with oral medication in the form of liquid
      formulation or tablets, 257 within the previous year. Of these, 43.2% reported
      difficulties in taking the medication. Only 8.5% of the treatments had been
      interrupted. The main cause of the problems were the medications' taste and
      difficulties with swallowing tablets. The problems were more pronounced among the
      younger children. The administration of tablets was more difficult than the
      administration of liquids. There was no relationship between the problems and
      frequency of dosing, duration of treatment, severity of illness, social status of
      the parents, or the parents' age. In conclusion, prescription of better tasting
      mixtures and chewable tablets may reduce the problems associated with
      administering oral medication to children.

PMID- 9599521
TI  - [Inhaled budesonide versus intramuscular dexamethasone in the treatment of pseudo
      croup].
AB  - We randomised 59 children hospitalized for croup to treatment with either inhaled
      budesonide or injected dexamethasone. Group A were treated with two inhalations
      of 1000 micrograms budesonide and group B received dexamethasone 0.6 mg/kg
      intramuscularly. We used a modified Westley-score, based on chest-wall
      retractions, barking cough, respiratory frequency and stridor. The children was
      aged three months to six years (mean 20 months). Three hours after the first
      treatment there was significant improvement in score amongst all children (p <
      0.001), but no difference between the two groups (p < 0.20). Six and 12 hours
      after the first treatment there were significantly better clinical scores in
      group B (p = 0.001, p = 0.0004). Based on this study we recommend dexamethasone
      0.6 mg/kg intramuscularly for children to be treated for croup.

PMID- 9599522
TI  - [Spread and control of methicillin resistant Staphylococcus aureus in a
      department of dermatology].
AB  - Patients with skin diseases caused a spread of methicillin-resistant
      Staphylococcus aureus (MRSA) to 17 patients in our Department of Dermatology,
      because of their heavily scaly skin. Patients with severe dermatosis are
      regularly treated with dicloxacillin. The resistance of bacteria strain concerned
      suggests a selection because of the use of dicloxacillin in the Department. The
      strain is sensitive to gentamicin, which differentiates it from strains imported
      from abroad. Increased hygienic precautions, isolation of infected patients,
      staff and management efforts and a close contact with the microbiologists
      prevented MRSA from spreading to other hospital wards.

PMID- 9599523
TI  - [Extended spectrum beta-lactamases in Danish Klebsiella isolates].
AB  - This study presents the first two cases of infections with Klebsiella pneumoniae
      producing extended spectrum betalactamases (ESBL) that have been recorded in
      Denmark. They presented as a urinary tract infection and a generalized infection
      in a patient admitted to an intensive care unit. Both patients had been treated
      with broad spectrum antibiotics prior to infection. Presumably, one of the
      strains had been imported from Turkey. The ESBL of the two strains were
      characterized as SHV-2 and SHV-5, respectively. Patients transferred from
      hospitals abroad should be screened for Klebsiella producing ESBL, in addition to
      MRSA and other multiresistant organisms. A restrictive antibiotic policy and
      strict hygienic precautions are essential measures to control the selection and
      spread of such organisms in the hospital environment.

PMID- 9599524
TI  - [General practitioners' prescriptions of antibiotics].

PMID- 9599525
TI  - [Kaposi sarcoma-associated Herpesvirus infection of dendritic cells in bone
      marrow in patients with myelomatosis].

PMID- 9599526
TI  - [The PKU registry and biobank at the National Serum Institute. Rules and
      applications].

PMID- 9599527
TI  - [On the possible influence of traffic offenders].

PMID- 9599529
TI  - [Vaccination against occupational hepatitis B].

PMID- 9599530
TI  - [Radiology on the Internet].

PMID- 9599531
TI  - [Surgical technique in Cesarean section. Evidence or tradition?].
AB  - The literature was reviewed in order to find clinical-epidemiological and
      physiological evidence for which surgical techniques should be preferred when
      performing Caesarean section. We found reasonable evidence for the following
      procedure: spontaneous placenta detachment, uterine repair in one layer and non
      closure of the peritoneum.

PMID- 9599532
TI  - [Neonatal lupus syndrome. Association with complete congenital atrioventricular
      block].
AB  - Neonatal lupus erythematosus (NLE) is characterized by persistent congenital
      complete heart block, often without any other structural heart defects. Lupus
      like dermatitis is seen transiently, more rarely hepatitis and thrombocytopenia
      occurs. Recent investigations have shown a close relation between NLE and
      maternal anti-Ro/La antibodies. These antibodies seem responsible for the
      destruction of the bundle of His and the AV node in the foetus. Total AV block is
      seen in 1:15.-22,000 of liveborn children, 70-90% of them are caused by NLE. It
      is difficult to identify the pregnancies at risk since at delivery most of the
      mothers (up to 66%) are without symptoms. If the mother has anti-Ro/La antibodies
      the risk for having a child with NLE is probably less than 5%. However, new
      investigations have shown that mothers who in addition have anti-DNA antibodies
      have significantly lower risk of bearing a child with NLE. In most cases foetal
      complete AV block is found accidentally during pregnancy. Slow foetal heart rate
      with the demonstration of AV dissociation should not, unless the foetus shows
      sign of incompensation, lead to acute delivery, but pregnancy should be monitored
      carefully by serial echocardiography. More than half of the children with
      congenital heart block need pacemaker therapy shortly after birth. The other
      children should be followed closely for signs of incompensation and may need
      pacemaker therapy later on.

PMID- 9599533
TI  - [Hepatitis B vaccination status among Danish physicians].
AB  - As part of a nation-wide questionnaire survey among Danish doctors, the incidence
      of hepatitis B vaccination was studied. For each specialty the findings were
      related to the risk of hepatitis B exposure assessed by the incidence of
      percutaneous and mucocutaneous blood exposure (PCE and MCE). A total of 6256 of
      9375 doctors (67%) responded and 6005 (64%) questionnaires were eligible for
      analysis. Only 34.3% of the doctors had been vaccinated against hepatitis B,
      ranging from 8.9% in Psychiatry to 56.9% in Obstetrics-Gynaecology. The annual
      incidence of PCE and MCE was high in surgical as well as non-surgical specialties
      with an average of 3.0 PCE and 3.9 MCE per person. In conclusion all doctors must
      be considered at risk of exposure to hepatitis B during part of or the entire
      career. The current level of hepatitis B vaccination is insufficient. Hepatitis B
      vaccination of all doctors before entering clinical work seems to be indicated.

PMID- 9599535
TI  - [Qualitative interview study on acceptance of influenza vaccination among the
      elderly].
AB  - Nine elderly men and women were interviewed in order to discover factors of
      importance in accepting influenza vaccinations. The study demonstrated that the
      fee to be paid by the patients was a considerable barrier to an improvement of
      the vaccination rate. The elderly informants were all aware that influenza
      vaccine is available. Some informants expressed uncertainty whether they
      themselves belonged to the risk groups who should be vaccinated. Sources of
      information were the general practitioner (GP), relatives, and the mass media.
      More personal information from the GP to persons at risk was wanted. Influenza
      vaccination behaviour was found to be consistent with the Health Belief Model.
      The present organization of influenza vaccinations does not promote a sufficient
      immunization rate. The threshold for accepting influenza vaccinations appears to
      be too high for the elderly population.

PMID- 9599534
TI  - [Influenza vaccination of the elderly in the municipality of Copenhagen].
AB  - In October/November 1996 all people living in the city of Copenhagen aged 70 and
      above were invited to receive an influenza vaccination. Of a total of 62,600
      people, 35,423 were vaccinated which is a participation rate of 56%. The
      participation rate increased with increasing age and in the older age groups the
      participation rate was 80%. The vaccinations were performed by nurses and most of
      the participants were vaccinated in special clinics (74.9%). Immobile
      participants were vaccinated either in their own homes (14.3%), in nursing homes
      (9.2%), or in hospitals (1.6%). One single case of hospitalisation of a
      chronically ill patient was registered, because of a weak influenza. No other
      side effects were registered. The total cost of all vaccinations was 4 million
      dkr. which is 115 dkr. (approximately 10 Pounds sterling) for each vaccination.

PMID- 9599536
TI  - [The effect of muscle training program for home care employees].
AB  - To assess the results of general muscle training for home helpers and home nurses
      we followed 40 women who completed a six month strength training program. All
      participants were employees at the home care district Skovgarden Hjorring. The
      training program consisted of exercises for all parts of the body. It was a
      general rehabilitation program and consisted of a teeterboard, a rubberband and a
      weight bag adjustable from one to six kg. The duration of the program was one
      hour. All participants were instructed in the training program by author Ulla
      Willadsen. The period of training lasted six months and was performed twice a
      week.

PMID- 9599537
TI  - [Providing patients with their diagnostic test results. A vignette study in
      general practice].
AB  - The communication of results of HIV tests and chest-X-rays because of persistent
      coughing are of particular interest because potential life-threatening disease
      may be disclosed. For HIV tests it is recommended that the result is communicated
      to the patient in the doctor's office face to face. In this questionnaire study
      based on two simulated case-stories with a 63 year-old man referred to chest-X
      rays because of persistent coughing, and a 27 year-old man, who had been living
      in Africa for some time, now wanting a HIV test performed, we found that only
      half (53%) of the general practitioners (GP) did communicate HIV test results in
      the consultation office. X-ray test results were only communicated in the
      consultation office by 18% of the GPs. Communication of test results which might
      have serious implications to the patient should preferably not be done by
      telephone. Patients should be told of potentially serious results in person by
      their own physician.

PMID- 9599538
TI  - [Role of Danish general practitioners in the prevention of AIDS].
AB  - The study describes Danish general practitioners' perception of their own role
      and their actual behaviour in the prevention of HIV/AIDS. Data collection was
      carried out by questionnaire and prospective registration of consultations
      dealing with HIV/AIDS during a two-week period. The results showed that most of
      the GPs (94%) were of the opinion that GPs should play a central part in the
      prevention of HIV, and 90% thought that the GP should take the initiative to talk
      about HIV. The median number of consultations dealing with HIV was two during ten
      working days (range 0-18), and more than half the GPs (56%) had not themselves
      initiated a conversation concerning the problem. The conclusion of the study is
      that there was discrepancy between the GPs' vision of their role in HIV
      prevention and activities in practice. It is recommended that initiatives are
      taken to strengthen the GPs' role in AIDS prevention.

PMID- 9599539
TI  - [Gene therapy of malignant brain tumors].

PMID- 9599540
TI  - [Radiographic picture of the month. Herpes simplex encephalitis].

PMID- 9599541
TI  - [How to remove a tick].

PMID- 9599542
TI  - [Fatal cases of methadone].

PMID- 9599543
TI  - [Ear temperature measurements at home].

PMID- 9599545
TI  - [Back pain--I'm surprised!].

PMID- 9599544
TI  - [Ambulatory tonsillectomy].

PMID- 9599546
TI  - [Back training--science and practice].

PMID- 9599547
TI  - [Palliative units in Denmark].

PMID- 9599548
TI  - [Animals as organ donors for humans].

PMID- 9599549
TI  - [Epidemiology of cancer pain].
AB  - The prevalence of pain in cancer patients is influenced by several factors, for
      example the cancer disease, stage of disease, metastases present and treatment.
      However, only very few studies take all these factors in account when presenting
      the prevalence of pain in cancer patients. Pain may be caused by direct tumour
      infiltration, but may also be indirectly related to the cancer disease, caused by
      the cancer treatment or unrelated to the cancer. The most frequent pain quality
      is somatic pain followed by visceral and neuropathic pain. Pain with certain
      qualities or characteristics, such as incident pain, tenesmi in the
      gastrointestinal tract or cramps located to the bladder or rectum are more
      difficult to relieve than other pains. Other factors, such as major psychological
      distress, fast increasing doses of opioids and a past history of addictive
      behaviour may also be predictive of a poor treatment outcome. Besides pain cancer
      patients may also suffer from other troublesome symptoms such as asthenia,
      anorexia, constipation, nausea and vomiting and poor quality of sleep. These
      symptoms have great impact on the patients' well-being and should be treated
      contemporarily.

PMID- 9599550
TI  - [AIDS-related non-Hodgkin lymphomas. Clinical picture and prognosis].
AB  - Patients infected with HIV are at high risk for developing non-Hodgkin's
      lymphomas (NHL). HIV-associated NHLs seem to be increasing in number. They
      consist of two major histopathological subtypes originating from B-lymphocytes:
      Burkitt-like lymphomas and diffuse large cell lymphomas. There seems to be a
      clear association between Epstein-Barr virus (EBV) and immunoblastic lymphomas (a
      subtype of large cell lymphomas) in AIDS patients. Patients with AIDS often have
      widespread disease at presentation and frequent involvement of extranodal sites
      (CNS, liver, bone marrow, the digestive tract and skin). The treatment of NHL in
      AIDS patients is controversial due to their poor response to chemotherapy as well
      as a tendency to develop severe hematological toxicity. Factors with a negative
      influence on the prognosis are: Extranodal localisation of NHL including CNS, CD4
      count below 200 x 10(6)/l, platelet count below 130 x 10(9)/l, widespread
      symptoms of disease, presence of EBV in the lymphoma and immunoblastic histology.

PMID- 9599551
TI  - [The role of diet for development of renal cell carcinoma].
AB  - Dietary risk factors for renal cell cancer were investigated in a population
      based case-control study of incident cases. A total of 351 cases and 340 controls
      matched for age and sex were interviewed about dietary habits as well as exposure
      to other known or suspected risk factors. An association was found between risk
      of renal cell cancer and energy intake, especially fats. There was no protective
      effect of fruits but a weak protective effect of cruceferous vegetables. The
      association with diet was present after adjusting for the effect of cigarette
      smoking, socioeconomic status and body mass index, all of which have been
      identified as risk factors for renal cell cancer.

PMID- 9599552
TI  - [Patients and attitudes to a palliative unit in H:S--a questionnaire study].
AB  - A questionnaire was mailed to 42 representative in-patient departments of
      hospitals in the City of Copenhagen asking the medical staff to state what number
      of their patients could possibly be referred to a future hospital--associated
      palliative care unit. All-together 215 answers were returned from two
      questionnaire dates two weeks apart, comprising more than 1750 patients each day.
      Furthermore, 42 of 60 general practitioners answered another questionnaire on the
      same topic. From the hospital questionnaire it was concluded that approximately
      8% of all patients were admitted for palliative care reasons, 75% suffering from
      incurable cancer. More than 50% of patients admitted for palliative care reasons
      were assessed to be suitable candidates for a palliative care unit. The general
      practitioners recognised at least 50 patients treated only for palliative
      reasons. In the same month the general practitioners referred more than 20
      patients to hospital wards, but two-thirds of the practitioners would have
      preferred that these patients could have had the option of staying at home for
      terminal care. In general, more than 50% of the medical staff opted for
      establishing a palliative care unit.

PMID- 9599553
TI  - [Psychological stress, occurrence of cancer and cause-specific mortality].
AB  - Psychological stress has been claimed to contribute to the onset of cancer and to
      increase mortality from a number of nonmalignant diseases. We investigated the
      effect of a genuine psychological stressor, i.e. cancer in a child, on the
      incidence of cancer and mortality from nonmalignant diseases of 11,231 parents in
      a Danish nationwide population-based study. The children were identified from
      records in the Danish Cancer Registry for the period 1943-1985; their parents
      were identified from population registers. Overall, 1665 parental malignancies
      were diagnosed from the date the cancer of the child was reported through 1992,
      as compared with 1702 expected from national incidence rates, to yield
      standardized incidence ratios of 1.0 (95% confidence interval, 0.9-1.0) for all
      parents, 1.0 for mothers and 1.0 for fathers. No excess mortality was seen from
      causes associated with allergic illness, autoimmune conditions, chronic illness
      or changes in behaviour. Our data provide no support for the hypothesis of an
      association between psychological stress and the incidence of cancer or mortality
      from nonmalignant diseases. We conclude that the human organism is highly
      adaptable, even to extreme psychological stress.

PMID- 9599554
TI  - ["Moon-cars" are dangerous].
AB  - We investigated the number and seriousness of moon-car accidents in our region (a
      moon-car is a toy-vehicle, see Fig. 1). The study was retrospective combined with
      a telephone-interview. Forty-seven patients were seen in the emergency room after
      a moon-car accident in the period 1/1 1990-31/12 95. There were 12 fractures,
      including five fractures of the tibial shaft and one supracondylar humeral
      fracture which was operated. There were 17 wounds, 14 of which were sutured.
      Seventeen patients had distorsions/contusions, three cases of head contusions
      (observed for concussion) and two with teeth damages. We found that the number of
      moon-car accidents is increasing (13 patients the last year), and that the
      accidents are not only minor. New rules in day care centres should be able to
      especially limit the number of more serious accidents.

PMID- 9599556
TI  - [Cervical necrotizing fasciitis].
AB  - Cervical necrotizing fasciitis is a rapidly progressive infection that involves
      the superficial and deep cervical fascia. Underestimation of this severe neck
      infection can delay diagnosis and treatment of this often fatal disease process.
      Three new cases, all with mediastinitis and fatal outcome are presented. Early
      diagnosis, aggressive surgical treatment and antibiotic therapy is essential if
      the high mortality rate is to be brought down in the future.

PMID- 9599557
TI  - [Comments to the picture of the month in Ugeskrift for Laeger nr. 9, 1998].

PMID- 9599555
TI  - [Do cardioselective beta-antagonists block the cardiac beta-receptor function
      also in the long run?].
AB  - As the human cardiomyocyte expresses both beta 1 and beta 2 adrenoceptors it is
      to be expected that the inhibition of one species of receptors can be
      counteracted by the other. This hypothesis was tested in 40 middle-aged men
      scheduled for coronary artery bypass surgery. Half the patients had been treated
      with cardioselective beta 1 antagonists for more than three months while the 20
      control patients had never been beta-blocked. The haemodynamic status after
      induction of a standardized fentanyl/midazolam anaesthesia and the sensitivity of
      the cardiovascular beta-adrenoceptors to isoprenaline titration were similar in
      both groups. In conclusion, patients chronically treated with cardioselective
      beta 1-blockers compensate for the perturbation to such a degree that their
      cardiovascular function is indistinguishable from patients who have never
      received beta-blockers.

PMID- 9599558
TI  - [A clinic for cancer genetic counseling].

PMID- 9599559
TI  - [Health and disease among children in Greenland].

PMID- 9599560
TI  - [Prognosis after perinatal asphyxia in full-term infants. A literature review].
AB  - Reviewing the literature published during the last 30 years we found comparable
      systematic studies of outcome for 1042 term infants born alive after likely
      intrapartum hypoxia-ischaemia. Fifty-two percent had no sequelae, 8% had
      developmental delay without associated handicaps, 4% had a single handicap, 11%
      were multihandicapped and 14% were dead as a consequence of the intrapartum
      hypoxia-ischaemia. The frequency of single handicaps exceeded the frequency found
      among the controls and in population studies. The frequency of children with
      developmental delay did not differ from that found among the controls. Outcome is
      closely related to the severity of hypoxic-ischaemic encephalopathy in the
      newborn.

PMID- 9599562
TI  - [Diseases and health problems among children in Greenland. An epidemiological
      study based on referrals to special pediatric care in eight different districts
      of Greenland 1992-94].
AB  - Epilepsy and asthma, especially non-severe asthmatic bronchitis, were the most
      frequent genuinely paediatric diagnoses among children referred to paediatric
      specialist examination. Atopic dermatitis was a substantial problem. A number of
      patients were probably suffering from sequelae of diseases, which can be
      prevented or treated. Among potential etiological factors may be mentioned
      perinatal asphyxia, infections, and neonatal hyperbilirubinemia including
      kernicterus. Postneonatally meningitis may be mentioned. Cerebral palsy and
      epilepsy were possible sequelae. Otitis media cannot be considered as genuine
      paediatric diseases, but nevertheless this was the most frequent diagnosis among
      children referred to paediatric examination. A few cases of rare diseases were
      seen, among these some specifically Greenlandic diseases, for instance familial
      Greenlandic cholestasis and familial hypoplasia of the adrenal cortex. Other
      health problems than diseases (Z-diagnoses) represented 24% of diagnoses made,
      among these fear of disease.

PMID- 9599561
TI  - [The spread of HIV in Greenland. Heterosexual epidemic--risk or reality? A 10
      year review of HIV transmission and preventive care].
AB  - With the first report of an HIV-positive Inuit in 1985 Greenland was considered a
      high risk area for a self-sustained heterosexual HIV-epidemic, due to high
      incidences of sexually transmitted diseases. In 1986 a national HIV-intervention
      programme began with two major aims: Firstly, improved STD treatment and
      incitation to change of sexual high-risk behaviour, secondly, close monitoring of
      HIV-antibody test activity, partner notification and repeated surveys of
      knowledge and sexual behaviour in selected populations. Very early the spread of
      HIV in Greenland became heterosexually transmitted and self-sustained, with
      repeated local small-scale epidemics in a subpopulation characterized by frequent
      STD's, alcoholism, lack of education and vulnerable social and economic
      resources. From 1994 to 1997 a marked increase in new cases was reported, and in
      November 1997 the total number was 76 HIV-positives in the Greenlandic population
      of 50,000 Inuits. The successful defeat of STD's, such as gonorrhoea and syphilis
      has not been followed by a change in sexual behaviour among the youth in
      Greenland. High incidences of genital chlamydial infections, early sexual debut
      and high frequencies of excessive promiscuity render Greenland an alarming
      potential for a future HIV-epidemic. This threat calls for an intensified
      national prevention programme, with close monitoring of the known HIV-positives
      and the potentially infected persons in the population at risk, and new campaigns
      to reduce high-risk sexual behaviour among the youth.

PMID- 9599563
TI  - [Long-term course among child psychiatric patients. A registry-based study of
      psychiatric morbidity and mortality among 546 Danish children].
AB  - A total of 546 children and adolescents, aged 5 to 15 years, who were admitted as
      in-patients to psychiatric hospitals throughout Denmark between 1970 and 1973,
      were followed up regarding to later readmissions and mortality. Approximately one
      third of the sample had at least one readmission after the age of 18 years: there
      was no significant difference between male and female subjects. Probands with
      three selected diagnoses, namely childhood neurosis, conduct disorder and
      maladjustment reactions, had a significantly greater general risk of readmission
      to psychiatric hospital in adulthood than the background population. In total, 24
      probands (22 male, and 2 female subjects) died during the study period. Eight
      subjects had committed suicide. The standard mortality rate was significantly
      increased.

PMID- 9599564
TI  - [Children from ethnic minorities in hospital in Aarhus. Why there--how long-
      because of what?].
AB  - We analysed the proportion of hospitalization, duration of hospitalization and
      diagnoses for children from ethnic minorities (both parents did not come from
      Nordic countries, EU, North America, New Zealand or Australia) compared to other
      ("western") children in a follow-up study. The study included all 47,987 children
      < 15 years in the municipality of Aarhus. All hospitalizations during March and
      April 1996 were recorded. The proportion of children from ethnic minorities who
      were hospitalized was 0.012, the corresponding proportion being 0.007 for the
      other children, showing a hospitalization-proportion-rate of 1.7 for the ethnic
      minorities. The median hospitalization time was two days and independent of
      ethnic group. In the group of ethnic minorities there were more children with
      psychological problems and with thalassaemia, and there were language problems in
      a third of the hospitalizations. The study showed a need for special health
      promotion activities for children from ethnic minorities.

PMID- 9599565
TI  - [Frequency of admissions to neonatal care units of 1994 birth cohorts in Funen
      and Frederiksborg Counties].
AB  - The frequency of admission to neonatal intensive care units is higher in Denmark
      than in the UK. The organization of the paediatric departments varies from county
      to county in Denmark. To investigate possible differences due to the
      organization, the records for all hospitalized newborns in a one year period in
      two counties (FR and FU) were studied. The rate of prematurity was higher in
      county FU than in FR, but, surprisingly, the admission rate was lowest in county
      FU. For full term infants the highest admission rate was found in county FR,
      where more infants were treated with nasal continuous positive airway pressure
      compared to FU. Short admissions were more common in FR. The on-call
      paediatrician is a senior doctor in FU, whereas it is a junior doctor in FR, and
      this could be a possible explanation for the differences between the two
      counties.

PMID- 9599566
TI  - [The effectiveness of in vitro fertilization. A cohort study of 300 couples].
AB  - A cohort of 300 couples, starting their first in-vitro fertilization (IVF)
      attempt between 1990 and 1992, were followed until completion of their treatment.
      A total of 897 treatment cycles were initiated. Of these 213 (23.7%) were
      cancelled, giving a total of 684 embryo replacements. One hundred and forty-one
      (47%) couples completed their treatment with delivery of at least one healthy
      baby. Ninety-eight (31.3%) couples completed their treatment without achieving
      delivery of a living baby, and 40 (13.7%) couples cancelled their treatment due
      to varying reasons. The treatment in seven couples was cancelled before
      completion due to medical reasons. In 12 women no transfer took place. IVF
      treatment is an effective procedure giving a "baby take home rate" of 47% within
      one to three cycles. A cohort study gives a realistic view of the probability of
      childbirth.

PMID- 9599567
TI  - [Risk of cancer among patients with cutaneous basal cell carcinoma].
AB  - A population-based cohort of 37,674 patients diagnosed during the period 1978
      1991 and registered in the Danish Cancer Registry with basal cell carcinoma of
      the skin (BCC) were followed for the occurrence of new malignancies. BCC patients
      experienced significantly increased cancer incidence rates compared with the
      general Danish population. The elevated cancer risk was not restricted to new
      cutaneous malignancies. Cancers at various sites, including lip, salivary glands,
      larynx, lung, breast, kidney and non-Hodgkin lymphoma occurred in significant
      excess. Patients diagnosed with BCC before the age of 60 years were at higher
      risk of developing new malignancies than patients diagnosed with BCC at an older
      age. This age association pertained particularly to breast cancer, testicular
      cancer and non-Hodgkin lymphoma.

PMID- 9599568
TI  - [Follow-up of patients after splenectomy at a local hospital].
AB  - We have studied the records of 79 patients splenectomised between 1965-1995 and
      questioned the 39 patients still alive regarding pneumococcal immunisation and
      measures against infections. Fifty percent of patients operated before 1978 had
      still not been immunised. Twenty-four percent of the patients operated after 1978
      were neither immunised at the hospital nor recommended this, and 10% had still
      not been immunised in 1995. Eight percent of the patients did not know that they
      had lost their spleen. Eighty-three percent of the patients had not been informed
      about measures against infection. Only 17% had penicillin available at home. We
      recommend that besides pneumococcal immunisation, special splenectomy cards and
      antibiotic prescription, splenectomised patients should be given written
      guidelines about dealing with infections and recommendations that pneumococcal
      antibody levels be controlled five years after the primary immunisation.
      Extraordinarily, hospitals should also inform previously splenectomised patients.

PMID- 9599571
TI  - [Wrong citation--wrong manuscript?].

PMID- 9599572
TI  - [Pravastatin--misinformation].

PMID- 9599569
TI  - [Arthritis as first symptom of leukemia in children].
AB  - Three children out of 30 (10%) referred for juvenile chronic arthritis had
      leukaemia. The patients had complained of intermittent musculoskeletal pain and
      painful joint swelling for three weeks, nine months and eighteen months prior to
      admission. On admission two of the patients had active arthritis with soft tissue
      swelling in one and three joints respectively. The third patient had only
      arthralgias and no joint swelling. All patients had slight anaemia, normal to
      slightly reduced thrombocyte count, slight neutropenia and absence of blasts in
      the peripheral blood. The correct diagnosis was made by bone marrow aspiration.
      Two children had acute lymphoblastic leukaemia and the third acute myeloblastic
      leukaemia. Leukaemia thus remains an important differential diagnosis in children
      presenting with musculoskeletal pain and/or arthritis.

PMID- 9599573
TI  - [Do you remember Benadryl?].

PMID- 9599574
TI  - Measuring DNA synthesis rates with [1-13C]glycine.
AB  - We have devised and evaluated a stable-isotopic method for measuring DNA
      synthesis rates. The probe is [1-13C]-glycine that is incorporated into purines
      via de novo biosynthesis. The human hepatoma cell line HEP G2 was grown in medium
      containing [1-13C]glycine, the cells were harvested at various times, and the DNA
      was extracted. Following hydrolysis to the nucleosides, a reversed-phase HPLC
      separation was used to provide separate peaks for deoxythymidine (dT),
      deoxyadenosine (dA), and deoxyguanosine (dG). The HPLC effluent was continuously
      fed into a chemical reaction interface and an isotope ratio mass spectrometer
      (HPLC/CRI/IRMS). The isotope ratio of the CO2 produced in the CRI was used to
      monitor for enrichment. The cells were grown continuously for 5 days in labeled
      medium and also in a 1-day pulse labeling experiment where the washout of label
      was observed for the subsequent 9 days. As predicted from the role of glycine in
      de novo purine biosynthesis, the isotope ratio of the pyrimidine dT did not
      change. However, for the two purines, dA and dG, the characteristic log growth
      behavior of the cells was observed in their 13C/12C ratios and good agreement in
      the doubling time was obtained for each type of experiment. Parallel experiments
      that measured the HEP G2 doubling time in culture using tritiated thymidine
      incorporation and direct cell counts were carried out compare to our new method
      with established ones. We believe that the use of [1-13C]-glycine and the
      HPLC/CRI/IRMS is a highly sensitive and selective approach that forms the basis
      of a method that can measure DNA synthesis rates using a nonradioactive, nontoxic
      tracer.

PMID- 9599575
TI  - Simultaneous detection of catecholamine exocytosis and Ca2+ release from single
      bovine chromaffin cells using a dual microsensor.
AB  - A dual microsensor with a 5 microns radius was fabricated to detect
      simultaneously Ca2+ and catecholamines following their secretion from individual
      biological cells. Detection of Ca2+ was based on changes in fluorescence as a
      result of its binding with a surface-attached dye, and catecholamines were
      detected by amperometry. The fluorescent dye employed, calcium green-1 dextran,
      is a selective chelator for Ca2+. It was attached to the tip of a carbon fiber
      electrode by cross-linking with 5% glutaraldehyde. The dual microsensor has a
      subsecond response time for both Ca2+ and catecholamine concentration changes.
      Ca2+ concentrations of 100 nM can be detected, while the detection limit for
      catecholamine is in the micromolar range. The utility of the dual microsensor was
      evaluated at the surface of bovine adrenal medullary cells. Release of
      catecholamines by exocytosis was evoked by transient application of histamine.
      This was detected by amperometry, and it was found to be accompanied by Ca2+
      release, as measured by fluorescence from the same sensor.

PMID- 9599576
TI  - Thick-film electrochemical immunosensor based on stripping potentiometric
      detection of a metal ion label.
AB  - A disposable electrochemical immunosensor based on potentiometric stripping
      analysis (PSA) of a metal tracer and using an entirely on-chip assay format is
      demonstrated. Challenges associated with the adaptation of earlier stripping
      voltammetric immunoassays to an on-chip operation, and with meeting the demands
      of decentralized testing, have been addressed. These include the surface
      immobilization of the antibody, the replacement of mercury drop electrodes,
      elimination of the separation and oxygen-removal steps, and the use of quiescent
      30-microL sample droplets. Human serum albumin (HSA) and anti-HSA antibody were
      used as a model system, while bismuth ion served as the metal label. The anti-HSA
      was immobilized onto the surface of a thick-film electrode, followed by a
      competition between the Bi-labeled analyte-tracer and the analyte (HSA) for the
      antibody binding sites. Upon removal of the unbound tracer, Bi3+ was released and
      detected by PSA. The dynamic concentration range for HSA (0.3-30 micrograms/mL)
      and the detection limit (0.2 microgram/mL, i.e., 90 fmol in the 30-microL sample)
      indicate that the greatly simplified protocol does not compromise the performance
      characteristics of stripping immunoassays. Consequently, this on-chip operation
      offers great promise for decentralized (clinical and environmental) applications.

PMID- 9599577
TI  - Plastic film carbon electrodes: enzymatic modification for on-line, continuous,
      and simultaneous measurement of lactate and glucose using microdialysis sampling.
AB  - Ring and split-disk plastic film carbon electrodes (PFCEs) were fabricated for
      use in thin-layer radial flow cells which were coupled to a microdialysis
      sampling system. PFCEs, were initially coated with osmium poly(vinylpyridine)
      redox polymer horseradish peroxidase (Os-gel-HRP). Then a second coat of oxidase
      enzyme was applied to produce enzyme bilayer (oxidase/Os-gel-HRP) PFCEs which
      were subsequently over-coated with cellulose acetate for use in the determination
      of glucose or lactate at 0 mV (vs Ag/AgCl). Split-disk electrode geometry enabled
      different oxidase enzymes to be immobilized on each half of a split-disk, Os-gel
      HRP-coated, PFCE to facilitate the electrochemically independent yet continuous
      on-line determination of these two analytes from a single dialysate. In
      continuous-flow experiments, cellulose acetate overcoated oxidase/Os-gel-HRP cast
      coated PFCEs were quick to stabilize background current and displayed linear and
      sensitive responses to substrates. The effect of ascorbic acid was minimal and
      cross talk between partner split-disk electrodes was demonstrated to be
      acceptable for in vivo applications. The utility of this analytical system is
      demonstrated by the quantitative on-line continuous assay of changes in dialysate
      striatal extracellular glucose and lactate from a conscious rat during (a) local
      stimulation of neurons by perfusion with the depolarizing agent, Veratridine, and
      (b) physical restraint.

PMID- 9599578
TI  - Phantom glucose calibration models from simulated noninvasive human near-infrared
      spectra.
AB  - The validity of published reports claiming to have successfully measured in vivo
      blood glucose from noninvasive near-infrared spectra collected in a time
      dependent manner is challenged on the basis of results obtained from a phantom
      glucose spectral data set. An in vitro model is used to simulate noninvasive
      human near-IR spectra. The phantom glucose data set is created by purposely
      omitting glucose in these modeled samples. Glucose values are then assigned to
      successive phantom glucose spectra, and multivariate calibration models are
      generated for glucose based on partial-least squares regression. As expected,
      calibration models are incapable of predicting glucose values when the glucose
      assignments are made randomly. Apparently functional models are obtained,
      however, when glucose assignments are made in a nonrandom, time-dependent manner.
      Prediction errors from these nonrandom models are essentially identical to those
      published by other as evidence of successful noninvasive blood glucose
      measurements. Chance temporal correlations between assigned glucose
      concentrations and some uncontrolled experimental parameter are responsible for
      this apparent model functionality.

PMID- 9599580
TI  - On-line dual microdialysis with ESI-MS for direct analysis of complex biological
      samples and microorganism lysates.
AB  - A novel dual-microdialysis approach has been developed for fast and efficient
      fractionation and cleanup for ESI-MS and ESI MS/MS analyses of biological
      samples. A modified dynamic microdialyzer utilizing two mirror-image serpentine
      channels, which sandwich a regenerated cellulose membrane of selected molecular
      weight cutoff, serves as the first stage for the removal of high-molecular-weight
      components and cellular residue. The second stage employs a hollow microdialysis
      capillary to remove low-molecular-weight species (e.g., salts) which can degrade
      or preclude analysis ESI-MS. A protein mixture consisting of 30 microM bovine
      serum albumin (BSA), 4.0 microM cytochrome c, 2.3 microM ubiquitin, and 9.4
      microM bradykinin in 0.5 M NaCl was used to evaluate the performance of this
      system. Essentially complete removal of both BSA and NaCl was achieved, resulting
      in high-quality mass spectra containing only the lower molecular weight proteins.
      After passing through the on-line dual-microdialysis system, a crude bacteria
      cell lysate yielded clean ESI-mass spectra in approximately 20 min. MS/MS of
      selected ions demonstrated abundant fragment ions and provided a second-dimension
      "fingerprint" of the complex cellular fraction. Preliminary application of this
      technique for direct characterization of microorganism lysates is presented.

PMID- 9599579
TI  - Determination of cannabinoids in water and human saliva by solid-phase
      microextraction and quadrupole ion trap gas chromatography/mass spectrometry.
AB  - Solid-phase microextraction (SPME) is applied to the determination of
      cannabidiol, delta 8-tetrahydrocannabinol (delta 8-THC), delta 9
      tetrahydrocannabinol (delta 9-THC), and cannabinol in pure water and human
      saliva. The inherent extraction behavior of the cannabinoids in pure water is
      evaluated along with optimization of the method in human saliva. The commercially
      available poly(dimethylsiloxane) (PDMS) SPME fibers were found to be the best
      class for the cannabinoid analysis. Partition coefficients were found to be
      extremely large for all of the cannabinoids (log K > 4.0). Equilibrium times for
      the 7- and 30-micron PDMS fibers were 50 and 240 min, respectively. A shorter
      extraction time of 10 min with the 30-micron PDMS fiber may be used for multiple
      extractions from the same vial, thus conserving the sample necessary for analysis
      and speeding up the total analysis time. Recoveries for the cannabinoids in
      saliva, relative to pure water, were dramatically improved by a method developed
      in our laboratory involving addition of glacial acetic acid to the sample vial
      prior to performing SPME. Using this method, recoveries relative to SPME in pure
      water ranged from 21 to 47% depending on the cannabinoid. The linear range for
      spiked saliva samples was established at 5-500 ng/mL (r2 > 0.994) with precisions
      between 11 and 20% RSD. The ultimate level of detection by SPME for the
      cannabinoids in saliva was 1.0 ng/mL, with signal-to-noise values of > or = 12. A
      saliva sample collected 30 min after marijuana smoking was subject to SPME and
      traditional liquid-liquid extraction analysis. Internal standard quantitation
      results for delta 9-THC by both methods yielded comparable results, indicating
      that the SPME method of analysis is highly accurate and precise. The level of
      delta 9-THC by SPME was found to be 9.54 ng/mL for the saliva sample.

PMID- 9599581
TI  - Combination of peptide profiling by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry and immunodetection on single glands or cells.
AB  - The combination of two sensitive and powerful analytical techniques on the same
      biological sample was examined: (i) matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS), which gives informative peptide
      profiling on complex samples such as organs or cells; (ii) immunological tools
      such as enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry to
      probe for specific peptides in biological extracts or cells. The cellular
      expression of the two precursors of the hyperglycemic hormone (cHH) was analyzed
      in neurosecretory cells (30-micron diameter) from the crayfish Orconectes
      limosus. Neurohemal organs were used to optimize the sample preparation and to
      demonstrate that, after peptide fingerprinting by MALDI-TOF MS, the sample can be
      recovered from the MALDI plate for further immunological analysis by ELISA. It
      was also established that, after immunocytochemistry following 4%
      paraformaldehyde fixation of the organ, the stained tissue could be recovered for
      further MALDI-TOF MS analysis. This dual characterization was successfully scaled
      down to the level of a single crayfish neurosecretory cell. Direct peptide
      profiling by MALDI-TOF MS on a single cHH-producing cell previously identified by
      immunocytochemistry demonstrated that both procHH isoforms were expressed in each
      cell analyzed.

PMID- 9599582
TI  - Collision-induced signal enhancement: a method to increase product ion
      intensities in MS/MS and MSn experiments.
AB  - Collision-induced signal enhancement (CISE), a new technique to enhance the MSn
      capabilities of the quadrupole ion trap, is demonstrated. CISE is based on the
      chemistry, i.e., the dissociation pathways, of the analyte examined.
      Polysaccharides up to hexamers are used to demonstrate the capabilities of CISE
      to enhance signal in two distinct functional modes. Mode 1 CISE is designed to
      enhance the signal of an ion desired for MSn analysis. Mode 2 CISE is designed to
      enhance structurally significant product ions in an MS/MS spectrum. Two different
      approaches can be utilized to effect the two functional modes of CISE. Both
      approaches use conventional resonant excitation techniques to effect
      dissociation, which is performed nonanalytically, i.e., without isolation of the
      ions to be dissociated. The two approaches are (1) single-frequency resonance
      excitation, and (2) broad-band wave form resonant excitation. Experimental
      results for Mode 1 CISE analysis demonstrate up to a 17.3-fold signal increase
      for the single-frequency approach and 5.3-fold using broad-band excitation. Mode
      2 CISE analysis shows up to a 16.3-fold increase in signal strength with single
      frequency excitation and 3.3-fold using broad-band excitation.

PMID- 9599583
TI  - Electrospray mass spectrometry studies of non-heme iron-containing proteins.
AB  - The oligomeric state and the metal atom stoichiometry of a series of non-heme
      iron-containing, multimeric proteins have been measured using electrospray
      ionization (ESI) in a time-of-flight (TOF) mass spectrometer. The proteins were
      obtained both from natural sources and by overexpression of recombinant DNA in
      Escherichia coli. ESI-TOF mass spectra of the metalloproteins present in
      nondenaturing solutions exhibit peaks corresponding to the multimeric forms of
      the holoproteins containing the expected number of metal atoms. Capillary-skimmer
      dissociation of the holoproteins produces a series of ions, which allows an exact
      count of the number of metal atoms present in each subunit, and also provides an
      indication of the oxidation state of the metal atoms. Two recombinant proteins,
      Phascolopsis gouldii hemerythrin (Pg-Hr) and Desulfovibrio vulgaris rubrerythrin
      (Dv-Rr), have been examined as well as hemerythrin isolated from Lingula reevii
      (Lr-Hr). ESI-TOF measurements of the aqueous solution of Pg-Hr at pH 6 yields
      ions of mass 108,783 Da, in close agreement with the calculated average molecular
      mass of an intact octameric holoprotein. Capillary-skimmer dissociation of the
      ions of the holoprotein produces a mass spectrum that contains peaks
      corresponding to a low m/z monomer and a high m/z heptamer. The masses of the
      monomer ions produced in this manner are assigned to the aposubunit, [subunit +
      Fe - 3H]+, and [subunit + 2Fe - 6 H]+. Naturally occurring Lr-Hr is composed of
      two subunits with average molecular masses measured under denaturing conditions
      by ESI-TOF to be 13,877.0 Da for the alpha-subunit and 13,517.5 Da for the beta
      subunit. Under nondenaturing conditions, a multimeric species with a molecular
      weight of 110,663 Da is measured by ESI-TOF, corresponding to an alpha 4 beta 4
      octamer. Capillary-skimmer dissociation of the alpha 4 beta 4 oligomer produces
      ions corresponding to both types of monomers (alpha and beta) and the
      corresponding heptamers (alpha 3 beta 4 and alpha 4 beta 3). In ESI-TOF
      measurements of recombinant rubrerythrin Dv-Rr using nondenaturing conditions,
      the principal ion observed corresponds to a homotetramer with an average
      molecular mass of 86,844 Da. Capillary-skimmer dissociation of the rubrerythrin
      tetramer leads to formation of a series of peaks corresponding to the subunit of
      the apoprotein and to subunits containing from one to three specifically bound
      iron atoms.

PMID- 9599584
TI  - Separation and identification of peptides in single neurons by microcolumn liquid
      chromatography-matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry and postsource decay analysis.
AB  - Microcolumn liquid chromatography (LC) was interfaced with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for
      separation and identification of peptides present in single neurons from the
      brain of the snail Lymnaea stagnalis. The nanoliter microcolumn LC effluent,
      mixed off-line with nanoliter matrix solution, was deposited onto the sample
      target every 60 s, producing fractions of approximately 145 nL in volume, which,
      upon drying, produced spots of approximately 1 mm in size. At the end of the
      chromatographic separation, fractions from the sample target were scanned by
      MALDI-TOF-MS. Identification of peptide peaks was achieved on the basis of LC
      elution order and mass information. Further identification based on sequence
      information was carried out for a native peptide fractionated by microcolumn LC
      from a single neuron with the postsource decay technique.

PMID- 9599585
TI  - Direct evidence of methylglucose lipopolysaccharides/palmitoyl-CoA noncovalent
      complexes by capillary zone electrophoresis-electrospray/mass spectrometry.
AB  - Mycobacterial methylglucose lipopolysaccharides (MGLPs) play an important
      regulatory role in the biosynthesis of long-chain fatty acids by forming
      complexes with neosynthesized acyl-CoA fatty acid derivatives. The MGLPs from
      Mycobacterium smegmatis were purified by high-performance anion-exchange
      chromatography and characterized by LSIMS and CE/ESI-MS. We investigated their
      interaction with palmitoyl-CoA using capillary zone electrophoresis with both
      direct and indirect UV detection. In the latter mode, the signal of the UV
      transparent MGLPs decreased upon addition of increasing amounts of palmitoyl-CoA;
      while using direct UV detection, the addition of palmitoyl-CoA to the MGLPs
      revealed characteristic profiles. The major peak was assigned to the noncovalent
      MGLP/palmitoyl-CoA complex on the basis of its electrophoretic mobility. The
      abundance of the complex was found to increase until the MGLP/palmitoyl-CoA molar
      ratio reached a 1/1 stoichiometry. The existence of and the stoichiometry of this
      complex were assessed by CE/ESI mass spectrum analysis, showing pseudomolecular
      ions of the MGLP/palmitoyl-CoA complex. These results confirm that CE/ESI-MS is a
      powerful tool to characterize noncovalent molecular association.

PMID- 9599586
TI  - Dielectrophoretic sorting of particles and cells in a microsystem.
AB  - There are highly sensitive analytical techniques for probing cellular and
      molecular events in very small volumes. The development of microtools for
      effective sample handling and separation in such volumes remains a challenge.
      Most devices developed so far use electrophoretic and chromatographic separation
      methods. We show that forces generated by ac fields under conditions of negative
      dielectrophoresis (DEP) can also be used. Miniaturized electrode arrays are
      housed in a microchannel and driven with high-frequency ac. A laminar liquid flow
      carries particles past the electrodes. Modification of the ac drive changes the
      particle trajectories. We have handled latex particles of micrometer size and
      living mammalian cells in a device which consists of the following four elements:
      a planar funnel which concentrates particles from a 1-mm-wide stream to a beam of
      about 50-micron width, an aligner which narrows the beam further and acts to
      break up particle aggregates, a field cage which can be used to trap particles,
      and a switch which can direct particles into one of two output channels. The
      electrodes are made from platinum/titanium and indium tin oxide (ITO) on glass
      substrates. Particle concentration and switching could be achieved for linear
      flow velocities up to about 10 mm s-1. The combination of this new method with
      high-performance optical detection offers prospects for miniaturized flow
      cytometry.

PMID- 9599587
TI  - Short-column liquid chromatography with hydride generation atomic fluorescence
      detection for the speciation of arsenic.
AB  - Increasing concerns over human exposure to arsenic and more stringent
      environmental regulations require rapid determination of trace levels of
      individual arsenic species, which presents an analytical challenge. We describe a
      method that is capable of speciating nanogram-per-milliliter levels of arsenite
      (As(III)), arsenate (As(V)), monomethylarsonic acid (MMAA), and dimethylarsinic
      acid (DMAA) within 3 min. Speciation of two common inorganic species in drinking
      water, As(III) and As(V), is complete in 1.5 min. The method is based on a
      combination of fast high-performance liquid chromatography (HPLC) separation of
      arsenic species on 3-cm HPLC guard columns and the sensitive detection of arsenic
      hydride by atomic fluorescence spectrometry. Detection limits for the four
      arsenic species in urine samples are 0.4-0.8 ng/mL. This simple method allows for
      the direct speciation of arsenic present in natural water samples and in human
      urine samples from the general population, with no need of any sample
      pretreatment. Our results from the determination of arsenic species in urine and
      water standard reference materials are in good agreement with the certified
      values of total arsenic concentration. The method has been successfully applied
      to speciation studies of metabolism of arsenosugars following the consumption of
      arsenosugar-containing mussels by human volunteers. Speciation of arsenic in
      urine samples collected from four volunteers after the ingestion of musseles
      reveals significant increases of DMAA concentration, resulting from the
      metabolism of arsenosugars. These results suggest that the commonly used
      biomarkers for assessing human exposure to inorganic arsenic, which are based on
      the determination of urinary arsenite, arsenate, MMAA, and DMAA, are not reliable
      when arsenosugar-containing seafood is ingested.

PMID- 9599588
TI  - Synthesis and characterization of new zirconia-based polymeric cation-exchange
      stationary phases for high-performance liquid chromatography of proteins.
AB  - Ion-exchange chromatography is a major method used for large-scale protein
      separations. New zirconia-based polymeric cation-exchange HPLC stationary phases
      have been developed for protein separations. Two routes were employed for the
      synthesis. In one method, polyethyleneimine (PEI) was adsorbed onto porous
      zirconia particles and cross-linked with 1,4-butanediol diglycidyl ether (BUDGE).
      Succinic anhydride was then reacted with the remaining primary and secondary
      amine groups on PEI to afford anionic functionalities. The second method utilizes
      poly(acrylic acid) anhydride as both the crosslinker and the stationary phase.
      The resulting stationary phases act to separate proteins by a weak cation
      exchange mechanism with a slight contribution to retention from hydrophobic
      interactions. In the presence of 20 mM phosphate buffer, Lewis acid/base
      interactions between the zirconia support and the proteins, which can
      significantly broaden the peaks, are sufficiently suppressed. The effects of
      ionic strength, mobile phase pH, and salt type are discussed. Protein mass
      recovery and loading capacity for protein separations on these phases have been
      evaluated. These weak cation-exchange stationary phases exhibit good stability
      under normal separation conditions for months and are stable in alkaline solution
      up to pH 10. In contrast to zirconia supports modified with small anionic
      species, these new phases have no limitation on the type of salt used as the
      eluent, and they exhibit unique selectivities. Therefore, they offer interesting
      alternatives for protein separations. To our knowledge, this work represents the
      first successful example of protein separations using porous zirconia-based
      polymeric phases under normal chromatographic conditions, which will definitely
      help make zirconia-based supports more useful for bio-separation.

PMID- 9599589
TI  - Gas-phase postderivatization following solid-phase microextraction for
      determining acidic herbicides in water.
AB  - This study analyzes acidic herbicides from an aqueous sample by developing a
      methylated postderivatization on the fiber following solid-phase microextration
      (SPME) with diazomethane gas procedure combined with GC/MS. Analysis results
      indicate that a silica fiber coated with polyacrylate (PA) yields a higher
      extraction efficiency than that obtained with poly(dimethylsiloxane) (PDMS) using
      the SPME technique. Detection limits are achieved at the level of 10-30 ng/L.
      Linearity is obtained over a wide range, with precision below 12% RSD. In
      addition, the significant reduction in extraction efficiency is attributed to the
      concentration of humic acids exceeding 5 mg/L. Various degradation compounds of
      acidic herbicides in basic solution are also detected, including 2,4
      dichlorophenol, 2,4,5-trichlorophenol, 4-chloro-3-methylphenol, pentachlorinated
      biphenyl, and tetrachlorinated biphenyl. Moreover, the amount of pentachlorinated
      biphenyl and tetrachlorinated biphenyl increases over time.

PMID- 9599590
TI  - Investigation of anion-exchange and immunoaffinity particle-loaded membranes for
      the isolation of charged organic analytes from water.
AB  - Anion-exchange and immunoaffinity particle loaded membranes (PLMs) were
      investigated as a mechanism for the isolation of charged organic analytes from
      water. Kinetic properties determined theoretically included dynamic capacity,
      pressure drop (delta P), residence and diffusion times (Tr, Td), and total
      membrane porosity (epsilon T). These properties were confirmed through
      experimental evaluation, and the PLM method showed significant improvement over
      conventional solid-phase extraction (SPE) and ion-exchange formats. Recoveries of
      more than 90% were observed for a variety of test compounds at flow rates up to
      70 mL/min (equipment-limited maximum flow rate). A fast-flow immunoaffinity
      column was developed using antibodies (Abs) attached to the PLMs. Reproducible
      recoveries (88% +/- 4%) were observed at flow rates up to 70 mL/min for the
      antibody (Ab)-loaded PLMs. Findings indicate increased selectivity over anion
      exchange PLMs and conventional SPE or ion-exchange methods and rapid Ab-antigen
      binding rates given the excellent mass-transfer characteristics of the PLMs.

PMID- 9599591
TI  - Solid-phase microextraction of monocyclic aromatic amines from biological fluids.
AB  - A solid-phase microextraction (SPME) protocol was developed for the quantitative
      analysis of monocyclic aromatic amines from biological fluids. The headspace SPME
      sampling technique was optimized for extraction and concentration of five target
      analytes (aniline, o-toluidine, 2-chloroaniline, 2,6-dimethylaniline, 2,4,6
      trimethylaniline) from urine, blood, and milk. The temperature, pH, and ionic
      strength of the matrix sample were modified to allow maximum adsorption of the
      analytes onto the SPME fiber. This method is rapid yet sensitive and can be
      completed in 15 min on a 5-mL sample. SPME/GC/MS analysis yielded good
      reproducibility (RSD > 11%) for each analyte from urine, blood, and milk. Method
      detection limits for the various biological fluids were determined and ranged
      from 0.40 ppb for 2,4,6-trimethylaniline in urine to 7.7 ppb for aniline in
      blood. This SPME sampling protocol can be applied to the biomonitoring of
      monocyclic aromatic amines from occupational, environmental, and medical
      exposure.

PMID- 9599592
TI  - Real-time microchip PCR for detecting single-base differences in viral and human
      DNA.
AB  - This report describes real-time 5' nuclease PCR assays to rapidly distinguish
      single-base polymorphism using a battery-powered miniature analytical thermal
      cycling instrument (MATCI). Orthopoxviruses and the human complement component C6
      gene served as targets to demonstrate the feasibility of using the MATCI for
      diagnosis of infectious diseases and genetic disorders. In the Orthopoxvirus
      assay, consensus Orthopoxvirus PCR primers were designed to amplify 266-281 base
      pair (bp) segments of the hemagglutinin (HA) gene in camelpox, cowpox, monkeypox,
      and vaccinia viruses. A vaccinia virus-specific fluorogenic (TaqMan) probe was
      designed to detect a single-base (A/G) substitution within the HA gene. In the C6
      gene assay, a 73-bp segment of the C6 gene was PCR-amplified from human genomic
      DNA, and TaqMan probes were used to detect a single-base (A/C) polymorphism in
      the second position of codon 98. The MATCI correctly identified the nucleotide
      differences in both viral DNA and human genomic DNA. In addition, using a rapid
      DNA preparation method, it was possible to achieve sample, preparation of human
      genomic DNA, DNA amplification, and real-time detection in less than 1 h.

PMID- 9599594
TI  - Sildenafil: an oral drug for impotence.

PMID- 9599593
TI  - Mechanical ventilation beyond the intensive care unit. Report of a consensus
      conference of the American College of Chest Physicians.

PMID- 9599595
TI  - Anthrax vaccine.

PMID- 9599596
TI  - Dolasetron for prevention of nausea and vomiting due to cancer chemotherapy.

PMID- 9599597
TI  - Health care CBA and CEA from 1991 to 1996: an updated bibliography.
AB  - OBJECTIVES: This article updates, through 1996, a previously published
      bibliography of health-care cost-benefit and cost-effectiveness analysis, which
      described the literature from 1979 to 1990. METHODS: A systematic search of
      MEDLARS databases was conducted for all articles falling under the medical
      subject headings "cost-benefit analysis" (which includes cost-effectiveness
      analysis) and "costs and cost analysis," as well as any article with the term
      "cost" in the title or abstract. All titles and abstracts were scanned to
      determine whether articles pertained to personal health services and whether both
      costs and consequences were assessed. If both criteria were met, the article was
      included in the bibliography. RESULTS: This search resulted in 3,539 eligible
      cost-benefit/cost-effectiveness analysis publications from 1991 through 1996.
      Publications were subdivided into two major categories: reports of studies and
      "other" publications, including reviews, descriptions of methodology, letters,
      and editorials. Reports of studies and "other" publications were classified into
      approximately 250 different topic areas. Studies were further classified by
      parameters such as study type, publication vehicle, and medical function. This
      article describes the results of this classification and describes trends during
      1991 to 1996 as compared with 1979 to 1990. OVERVIEW OF CONTENTS: The entire
      bibliography is reproduced in Appendix A. The classification of study reports and
      "other" publications into topic areas is presented in Appendix B, with numbered
      references to all bibliography entries. Detailed tables of findings are presented
      in Appendix C, and the results are illustrated graphically in Appendix D.

PMID- 9599598
TI  - Are we ready to use cost-effectiveness analysis in health care decision-making? A
      health services research challenge for clinicians, patients, health care systems,
      and public policy.
AB  - The dominance of managed care as an organizing principle for health care delivery
      suggests that cost-effectiveness analysis (CEA) may be applied increasingly to
      decision-making at all levels. Health services researchers now need to address
      questions of how to further the underlying methods of CEA, how to make it a more
      practical tool for market-based as well as public policy decisions, and how to
      enhance CEA's ability to lead to responsible decisions that result in more
      effective and efficient care.

PMID- 9599599
TI  - [Mechanism of the primary radiobiologic action].
AB  - Basing on the well-known high sensitivity of the biological processes to
      alteration of pH of a medium it is assumed that one of the major factors of
      primary biological effect of ionizing radiation is the increase of acidity in
      charged particle's tracks. This makes possible to understand the mechanism of
      protective action of various radioprotectors and the extremal experimental
      dependence of RBE vs LET has been explained. The position of corresponding
      maximum was estimated as approximately 10 eV/A in accord with experimental data.

PMID- 9599600
TI  - [Current problems of neutron radiobiology].
AB  - A brief review of up-date problems of neutron radiobiology, related to neutron
      therapy development and setting up of radiation safety standards for neutrons, is
      present. The main attention is paid to the effects of combined gamma-neutron
      irradiation, peculiarities of reactor neutrons biological action and new
      approaches in neutron capture therapy. On the basis of own and literature data
      the results of cellular and whole-body studies as well as the applicability of
      biophysical modelling for description and interpretation of experimental data are
      discussed.

PMID- 9599601
TI  - [The concept of synergism in radiobiology].
AB  - The definitions and various quantitative estimations of synergistic effects are
      presented. Common regularities of synergistic interaction under combined action
      of different harmful environmental agents are summarized. Possible mechanisms and
      mathematical models for prognosis and optimization of the synergistic effect are
      discussed. The data related with the dependence of synergy on intensity of agents
      applied are analysed. On this basis, it is concluded the fundamental importance
      of synergistic interaction at low dose rate of ionizing radiation and/or low
      intensity of UV light.

PMID- 9599602
TI  - [Problems of radiobiology at the end of the 20th century].
AB  - The modern radiation biology is characterized by an increased interest in the
      effects of small doses. Some investigators consider the small doses of radiation
      as having the larger damaging efficacy than the higher doses, the majority of
      researchers hold the opinion of their decreased danger, while some scientist
      favor the hypothesis of hormesis the positive effect of the small doses of
      radiation exposure. The article describes new approaches to the development of
      the unified scientific strategy for resolving this problem.

PMID- 9599603
TI  - [Molecular mechanisms of autorepair of DNA double strand breaks].
AB  - The physical mechanism of interaction between nucleotides in intracellular liquid
      medium was studied. It was shown that during the contact between the thymine and
      guanine there exists a potential barrier the distance of about 10 A, which
      prevents the enzyme self-repairing in DNA after a double damage. All the
      remaining pairs of nucleotides have no such a barrier. Some processes of self
      repairing of DNA for various types of double damages are analyzed. The geometry
      of an irreversible damage of DNA was determined. It was shown that with the
      increase in the number of hydrated electrons diminishing of the viscosity and
      increase in the temperature of intracellular medium the barrier vanishes and DNA
      undergoes a complete self-repairing.

PMID- 9599604
TI  - [Free radical mechanisms of radiation modification of DNA sugar fragment].
AB  - Analysis of the DNA and modeling its certain fragments substances radiolysis data
      allows to attribute the cardinal role to the primary 2-deoxyribosyl radicals in
      the processes of the breaks (C'3, C'5) and alkali-labile sites (C'1, C'2, C'4) in
      DNA strands, of the free bases appearance (C'3, C'5). The higher yield of bases
      destruction in DNA is explained by the transferring of a damage (unpaired
      electron) from 2-deoxyribosyl to a base within one nucleotide.

PMID- 9599605
TI  - [Various biochemical determinants and radioresistance markers in the mammalian
      body].
AB  - The authors data about the relationship between the organism radioresistance
      (survival/lethality after lethal doses of irradiation) and RNA/DNA ratio, DNA
      repair activity in blood cells (that damaged with chemical mutagen, UV- and gamma
      rays) and also with oxygen radical forms generation in mononuclear and
      polymorphonuclear blood leucocytes for allogen molecules and bodies inactivation
      were resumed. Significance of considered correlation was higher after leucocyte
      mobilization by bacterial lipopolysaccharide injection. The founded relationship
      between the biochemical processes and survival (radioresistance) was confirmed on
      the animal radioresistance/radiosensitivity model, when one give to animals the
      substances in radioprotective effective or not effective doses. The chromatin
      expression level and the activity of oxygen radical forms generation systems were
      considered as the biochemical determinants of radioresistance, and their values-
      as the markers of this status.

PMID- 9599606
TI  - [Systemic radiation reaction of tumor cell populations to high dose irradiation].
AB  - The work presents the results of the experiments confirming supposition of
      existence of a protection mechanism opposing hard destruction effects and acting
      at cell population level. The experiments were carried out with cultures of
      tumour cells HeLa and DEF 4/21. By technique of hybrid selection in selective HAT
      medium it was found that radioinduced cell fusion led to formation of viable and
      clonogenic cell hybrids. By electron microscopic methods, microinjections of
      fluorescent dye-stuff into cells and autoradiography it was discovered that tight
      cell communications were formed in irradiated culture before cell fusion. After
      high dose radiation posterity of survivor cells was by far the most
      radioresistant comparing with the parent cells and had more greater ability for
      repopulation. It was supposed that the ability was based on property of rapid
      transition from mitotic reproduction to non-mitotic division.

PMID- 9599607
TI  - [Is apoptosis a "programmed cell death"?].
AB  - Many authors consider apoptosis as a programmed cell death (PCD). Their opinion
      is based usually on the dependence of cell death on the protein-opinion and RNA
      synthesis, on the intranucleosomal fragmentation of DNA and on the expression of
      genes, which can induce apoptosis. However our analysis of numerous literature
      data on the apoptotic death (judging by their morphological criteria) of
      different cell kinds induced by various agents shows: internucleosomal
      fragmentation of DNA is neither a trigger, nor a reliable proof for apoptotic
      death; protein- and RNA synthesis, as well as expression of P53 genes is also not
      a necessary condition for that and is important only in some combinations of the
      cell type and state and the nature of the damaging agent. Thus, the existence of
      immanent cell death program requires some more proofs and for present the term
      PCD may be undoubtedly attributed only to the genetically determined processes
      intended to remove such cells and organs which become unnecessary for the
      following development, in short, PCD is a term on the level of organism. We
      propose that character and sequence of destructive processes at apoptotic cell
      death are conditioned by the conformational changes in genome as result of the
      cellular environment changes caused by the action of damaging agents on the
      cellular membranes.

PMID- 9599608
TI  - [Biophysical modeling of radiation damage in DNA and chromatin induced by
      radiation of varying quality].
AB  - DNA double strand breaks in chromatin induced by high LET ionizing radiation are
      analysed on the basis of biophysical modelling and computer simulation.
      Theoretical and experimental data are presented arguing in favour of nonrandom
      clustered distribution of DNA double strand breaks in chromatin.

PMID- 9599609
TI  - [Cytogenetic damage and mutagenesis in mammalian and human cells induced by
      ionizing radiation with varying LET].
AB  - Base oneself on analysis of literature and proper data the conclusion was
      inferred about essential role of structural chromosomal (and gene) damages for
      radiation-induced mutagenesis of mammalian and human cells (for example HPRT
      loci). The evidences are adduced of their increase role in mutagenesis after
      influence of ionizing radiations with high LET. The consequences of HPRT-gene
      damages have been examined hypothetically.

PMID- 9599611
TI  - [Genetic effects of chronic irradiation of low intensity].
AB  - The report reveals the results of genetic studies of biological consequences of
      Chernobyl NPP accident and experiment with low radiation carried out in 1986-1996
      years. The report deals with the results of cytogenetics observation of
      "liqudators" and data of genetic analysis of some laboratory strains of
      Drosophila melanogaster. It supposed, that the alteration level of mutability may
      be explained in destabilization of genotype. The essential part in induction of
      genotype destabilization replies the genome instability mechanisms.

PMID- 9599610
TI  - [Relationship between transcription and repair of radioinduced DNA damage].
AB  - The DNA repair is occurred on genome level with different rates. This rates are
      depend on a transcription activity of various genome sequences. The repair rates
      are low in non-transcribed genes and DNA sequences, more higher in transcribed
      genes and the highest in actively transcribed strands of active genes. Such
      classification could be applied to the repair of UV-induced cyclobutane
      pyrimidine dimers and for other (but not for all) DNA lesions. This observation
      has become a basement of such important findings as involvement of transcription
      into repair or existence of transcription-coupling repair factors (i.e. TFIIH).
      Thymine glycoles which are appear under ionizing radiation exposure, are repaired
      preferentially in transcribed DNA. In present reviewer we observe the
      preferential repair of ionizing radiation-induced single strand breaks (SSBs) in
      transcribed DNA of human cells. Discontinuous distribution of DNA repair along
      hole genome has a grate role in biological processes. The data, obtained on cells
      from patient with rare hereditary disease Cockayne syndrome have shown that there
      is the defect of preferential repair of pyrimidine dimers and ionizing radiation
      induced thymine glycols and SSBs in transcriptionally active DNA sequences. In
      case of another rare hereditary disease-ataxia telangiectasia the defect of
      preferential repair of ionizing radiation-indiced SSBs was observed. The defect
      of preferential repair of radio-induced damages in AT and CS cells can explain
      such fishers of this diseases as high sensitivity to ionizing radiation.

PMID- 9599612
TI  - [Somatic mutagenesis as a biological dosimeter of radiation exposure].

PMID- 9599613
TI  - [Features of DNA repair during chronic exposure to mutagenic factors].
AB  - Long-time in vivo influence of chemical mutagens in low doses can decrease the
      level of unscheduled DNA synthesis (UDS) induced in human as well as in
      laboratory mammals. The phenomenon under investigation is not specific neither
      for chronically acting mutagens nor for challenging agent. A decrease in UV- and
      gamma-ray-induced UDS was registered after chronic irradiation in plant
      populations and also in Chernobyl ameliorators and inhabitants of radioactively
      contaminated regions. The observed effect seems to have general biological
      character.

PMID- 9599614
TI  - [Integral estimation of genetic effects of ionizing radiation].
AB  - A system of criteria (direct, indirect, extrapolational, integral, populational,
      evolutional) has been proposed to estimate the consequences of irradiation of
      flora, fauna and human population. This system makes it possible to obtain the
      most comprehensive estimate of genetic effects from exposure of live organisms to
      ionizing radiations. An attempt has been made to use extrapolational approaches
      for assessing the genetic risk on the basis of the results of cytogenetic
      examination of the human population in a number of regions exposed to the action
      of ionizing radiations as a result of the Chernobyl accident, in connection with
      the activity of the chemical plant Mayak in the Chelyabinsk region, nuclear
      explosions at the Semipalatinsk nuclear test site, the accident at the Three Mile
      Island nuclear power plant in the U.S.A.

PMID- 9599615
TI  - [Secondary biogenic radiation of gamma-irradiated human blood].
AB  - The samples of blood freshly taken from healthy men were gamma-irradiated with a
      dose of 10 Gy. It was shown that after the treatment the blood gained the
      capacity to emit secondary biogenic radiation. Emission lasted for some hours,
      passed through quartz-glass cuvette and was revealed by stimulating influence on
      biological detector (sprouting seeds).

PMID- 9599616
TI  - [Reaction of the hematopoietic system under long-term emotional stress developed
      after preliminary gamma-irradiation with low doses].

PMID- 9599617
TI  - [Cytokines in the aspect of pathogenesis and therapy of acute radiation
      sickness].
AB  - The statement about dominating role of stem cell failure (exhaustion) in acute
      radiation bone marrow syndrome outcome needs to be changed. Cytokine-producing
      cells lacking reactivity that prevent usage of stem cell compartment reserves can
      play important role in immunohemopoiesis radiation damage.

PMID- 9599618
TI  - [Radiation and immunity. Contemporary view of old problems].
AB  - Some key problems of radiation immunology which were formulated during last
      decades have been considered. The possibility or their decision appeared at
      recent time proceeding from the new view on the ionizing irradiation as a source
      of biologically significant signals. From that point of view some experimental
      data concerning radiation effects on the maturation and selection of lymphocytes,
      contact interaction of immune system cells and cytokine network were reviewed. It
      was concluded that the disturbances of the spatial and temporary organization and
      integrative functions of immune system were the results of the non-adequate
      radiation-induced signalling.

PMID- 9599619
TI  - [Current issues in clinical radiobiology and ways of resolving them
      experimentally].
AB  - Information being collected for some tens year in frame of clinical study of
      radiation effects in man in broad range of dose and exposure variants has been
      summarised and systematized. It has been formulated the questions which could be
      answered under only clinical observation with many difficulties: diagnostical and
      prognostical criteria for evaluation of therapy efficiency in non-bone marrow
      syndrome of acute radiation disease choice and conformity of methods of bone
      marrow syndrome therapy in overlethal range of dose; improving of preclinical
      examination of means and methods of acute radiation syndrome prophylaxis and
      treatment; comparative analysis of the role of various radiation factors in
      development of oncological and severe somatic diseases and possibility of these
      effects modification. Some limitations in extrapolation of experimental data onto
      clinical practice has been discussed and optimal forms of cooperation are shown.

PMID- 9599620
TI  - [Ionizing radiation and 5-bromo-2'-deoxyuridine as tools for analysis of the
      fundamental mechanism of aging in animals].
AB  - The influence of gamma-irradiation and 5-bromo-2'-deoxyuridine (BUDR) on the life
      span and behaviour (in photoactivity test) of D. melanogaster was studied. It was
      found that gamma-irradiation resulted in decrease of life span. However the form
      of survival curves changed only under exposure to doses higher than 500 Gy.
      Treatment with BUDR distorted the form of survival curves and caused death of
      insects immediately after exclusion. It also caused abrupt decrease in
      photoactivity of insects, while irradiation even with very high doses did not
      affect this feature. It is proposed that initiating substrat in drosophila aging
      is DNA of nerve cells. The possible relationship between aging regularities and
      evolutional extinction of eucaryotic species is discussed.

PMID- 9599621
TI  - [Molecular and cellular mechanisms of late radiation injuries].
AB  - Late radiation damages arise more often in nonproliferating or slow proliferating
      tissues after local irradiation in large (intolerable) doses of ionizing
      radiation. Obviously the late radiation effects are induced by radiation damages
      to capillaries and disturbances of microcirculation in tissues. This is a basis
      for tissue hypoxia, "oxidative stress" and loss of parenchyma cells. The direct
      radiation effect on parenchyma cells has as a rule little importance for
      production of late radiation damages. Other type of late radiation damages can be
      discovered after sublethal irradiation of whole body. This is a cause of decrease
      of life span. In this case the important factors are also damages of vessels,
      disturbances in microcirculation and loss of parenchyma cells in "target" organs
      especially in neuroendocrine and immune systems. The new data on the possibility
      to decrease the late radiation damages after local or whole body irradiation
      using postradiation treatment with pulsed electric field (PEF) are considered.
      Mechanisms of PEF effects are explained in terms of its ability to induce nitric
      oxide production which causes intensification of blood microcirculation, as well
      as increase in SOD production and activity of repair enzymes.

PMID- 9599622
TI  - [Evaluation of biological sequelae for cattle in the zone of the Chernobyl
      accident].
AB  - The influence of Chernobyl NPP outburst on cattle from farms in Russia and
      Belorussia was examined since 1988 to 1996. Changes in the level of thyroid
      hormones and imbalance in cAMP/cGMP ratio with increased cAMP concentration in
      blood were found. The content of cAMP and E, F2a prostaglandins was varied
      because of the disturbances in the rate of their metabolism. Two critical periods
      of pregnancy in cows were revealed. In the first half of pregnancy (the 4th-5th
      month) disorders in thyroid prevailed. In the second half (7th-9th month) changes
      in testosterone, progesterone, estradiol and estriol concentration were the most
      actual.

PMID- 9599623
TI  - [Radioadaptive response in lymphocytes of children living in territories polluted
      by radionuclides as a result of the accident at the Chernobyl power plant].
AB  - The radioadaptive response and antimutagenic action of lymphoblastoid interferon
      in the human blood lymphocytes of the children from polluted after Chernobyl
      accident Bryansk region were studied. Cells pretreated with tritiated thymidine
      with 2 Gy of gamma-rays at 20 h of culture after PHA-stimulation on seven of the
      ten donors result in lack of radioadaptive response. On testing some of them (4
      donors) no protective adaptive response was found, others (3 donors) pretreated
      with tritiated thymidine gave sensibilization. Significant decrease in interferon
      antimutagenic activity in lymphocytes with disturbed adaptive response was also
      found. It has been proposed that there is similarity or identity of mechanism of
      radioadaptive response and of non-repair component of interferons antimutagenic
      action.

PMID- 9599624
TI  - [Genetic disorders in house mice after the accident at Chernobyl power plant].
AB  - Genetic effects were studied in house mice caught from 1986 to 1994 in regions
      polluted by radionuclides as a result of the Chernobyl disaster. The dose rates
      of gamma-radiation on the soil surface ranged from 0.02 to 200 mR/h. The
      frequency of reciprocal translocations in mouse spermatocytes was relatively low,
      but increased with the dose rate. Embryo mortality was increased only in the
      progeny of male mice caught in 1987 in the area with maximum contamination. The
      frequency of mice heterozygous for recessive lethal mutations decreased with the
      time after the accident.

PMID- 9599625
TI  - [Fungal infection of human organs by resistant melanin-synthesizing species is
      one of the pathogenic factors and one of the real consequences of the accident at
      Chernobyl power plant].
AB  - Free radical melanin centers have been detected in the cell concentrate of
      bronchoalveolar lavage (BAL) of liquidator of Chernobyl NPP accident. To identify
      the nature of these centers the EPR technique and the fluorescent technique were
      used to study BAL of liquidators with lung chronic pathology, their blood, blood
      components as well as model melanin- and lipofuscin-containing systems: synthetic
      DOPA-melanin, human melanosome, human lipofuscin, human melanolipofuscin. I
      Besides that we have investigated the samples of fungi, extracted from lung
      phlegm of liquidators (Aspergillus niger, Aspergillus fumigatus, Aspergillus
      flavus, Penicillium Sp., Candida albicans) as well as the melanin, extracted from
      fungal conidium. It has been shown that the melanin centers found in BAL cells of
      liquidators is the melanin of melanin-synthesizing mutant fungi Aspergillus
      fumigatus and Aspergillus flavus. The prolonged gamma-irradiation at low dose
      rate and the effects of inhaled radioactive particles cause the adaptive mutation
      of micromycetes producing the chemo- and radioresistant population. We think that
      the radioactive dust and pathogenic mutant micromycetes were inhaled in lungs of
      liquidators during their work at the Chernobyl NPP. Thus, one of valid
      consequences of Chernobyl accident may be the wide fungous of human organs, in
      particularly, by Aspergillus mutant. The radiation-induced weakening of immune
      reactions of liquidators promotes the resistance of this fungus mutant infection.

PMID- 9599626
TI  - [Radioecological sequelae to the accident at Chernobyl power plant for fish].
AB  - The estimate of dynamics in concentration of radionuclides in muscles of some
      game-fish from Kiev reservoir and lakes in Bryansk region for period after
      Chernobyl accident was carried out. The concentration of 137Cs in fish has not
      exceeded the admissible concentration (600 Bq/kg ww) since 1993. The exceptions
      are the cooling-pond of Chernobyl NPP and Kozlanovskoe Lake where the
      concentration of 137Cs in fish's muscles exceeded the admissible level more than
      5-6 times even in 1995. It was concluded that chronic irradiation of game-fish in
      water bodies outside 30-km zone would not affect the volume of fishing.

PMID- 9599628
TI  - [Chemical protection from ionizing radiation of low intensity].
AB  - It was shown that natural protectors are perspective preparations under low-level
      ionizing irradiation. Natural protectors influence regulatory systems of exposed
      organisms, mobilize endogenous background of radioresistance and intensify the
      total non-specific resistance of organism. Natural protectors are low- or
      nontoxic preparations and can be used with food.

PMID- 9599627
TI  - [Consequences of radioactive pollution of forests in the zone affected by the
      accident at the Chernobyl power plant].
AB  - The effect of forests on the radionuclide primary distribution in different
      components of the contaminated ecosystems is considered by the example of
      Chernobyl accident. A basic mathematical model is developed describing 137Cs
      biogeochemical cycling under conditions of quasi-steady state radionuclide
      redistribution in the ecosystem. The radionuclide fluxes between different
      ecosystem components are estimated. Forest ecosystems are proved to diminish
      radionuclide migration in the environment, and forest should be regarded as an
      important sanitary factor. The contribution of contaminated forests and forest
      products to the total irradiation dose to local population is estimated. Special
      countermeasures are elaborated in order to diminish unfavorable consequences of
      forest radioactive contamination. A long-term dynamics of radioactive situation
      in the forest ecosystems is forecasted and further studies on the subject are
      drafted.

PMID- 9599630
TI  - [New standards for radiation safety and effective dose].
AB  - The scientific bases and the peculiarities of the new radiation safety standards
      (RSS) implemented in Russia in april 1996 are considered. A comparison is made of
      the merits and shortcomings of both conceptions of standardization--by means of
      setting dose limits for the critical organs or by means of limiting the effective
      dose as a measure of the total radiation risk of late effects. The application of
      the effective dose to practice gives unquestionable advantages for assessing the
      sufficiency of arrangements providing radiation safety of personnel or public
      protection against radiation. However the use of the effective dose for
      individual dose monitoring is often not good (especially in the case of internal
      irradiation) due to wide variation caused by oversimplifications in the applied
      models. Essential shortcomings of the RSS-96 are also the absence of the
      permissible body burden of radionuclides among the derived standards and the
      regulation of the mean annual (unmeasurable) values of their concentration in
      air. It is proposed in addition to the effective dose which limits the risk of
      stochastic effects to reserve in the RSS the limits of equivalent doses for the
      main body organs (lungs, liver). This would eliminate the deterministic effects
      and give the possibility of differential evaluation of the irradiation pattern.
      It is also proposed to replace the reglamentation of mean annual concentrations
      of radionuclides in air by the reglamentation of their permissible concentration
      in the working zone.

PMID- 9599629
TI  - [Use of a preparation of natural origin to attenuate biological effects under
      conditions of radioactive pollution and in a radiobiological experiment].
AB  - The experiments in animals exposed in the area of increased radiation level
      around the Chernobyl NPP and the observational data on laringosyndrom and
      peripheral blood pattern of the people, who worked at the Chernobyl NPP in 1986
      1987, have shown that it is possible to use some biogenic preparations (e.g. MIGI
      K) for protection under chronic exposure to natural and technogenous ionizing
      radiation. MIGI-K preparation effectively enhances radioresistance as well as
      general resistance of the organism. It has important positive characteristics: it
      is non-toxic, there are no side effects and contra-indications for its peroral
      use as a nutriceutic, it has no mutagenic properties, it has not only
      radioprophylactic but also radiotherapeutic activity and pronounced cancerostatic
      activity. It is also important that MIGI-K has long-term effects on the organism
      resistance (up to 2 weeks after the ending of its month course), enhances the
      endogenous background of radioresistance, shows hemoregulatory effects,
      intensifies radionuclide efflux from organism. It can be stored under room
      temperature for several months without the loss of its activity. The data
      mentioned above let us to conclude that MIGI-K is adaptogenous preparation with
      wide spectrum of activity.

PMID- 9599631
TI  - [Human being in an electromagnetic field (present situation, expected bioeffects
      and evaluation of danger)].
AB  - The reference of EMF sources which are affecting human-beings was produced.
      Taking into consideration scientific data on the radio biological non-ionizing
      radiation the electromagnetic danger for people was estimated.

PMID- 9599632
TI  - [Optimization of radiation protection in the agrosphere: methods of optimization
      and computer systems for decision support with respect to management of
      protective measures].
AB  - Principles and methods of radiation protection optimisation for countermeasure
      implementation on areas subjected to radioactive contamination are discussed.
      Methodological aspects of the protective measures analysis in agrosphere are
      presented. Methods of estimation of intervention levels, examples of assessment
      and comparison of countermeasure effectiveness with the use of various criteria
      are considered. The brief review of up-to-date decision support systems is
      submitted along with the description of computer system PRANA DSS for estimation
      of the consequences and countermeasures management in agrosphere in the long-term
      period of liquidating the consequences of a nuclear accident.

PMID- 9599633
TI  - [Should we screen for prostate cancer?].
AB  - The controversy concerning the justification for prostatic cancer screening is
      now about ten years old. It is the consequence of several convergent phenomena:
      the routine use of new diagnostic tools such as prostate specific antigen, ageing
      of Western populations, increased life expectancy and finally public health
      economic aspects. Is screening justified before the age of 50 years? The answer
      is no, except in high-risk families with several cases of prostatic cancer, in
      which screening should be started at the age of 40 years. Is screening justified
      after the age of 70 years? The answer is no, except in men between 70 and 75
      years whose general state and physiological age suggest that they have a life
      expectancy exceeding ten years. Is screening justified between 50 and 70 years?
      There is no global "medico-economic" answer to this question, as medical truth,
      i.e. the individual's interests, appears to be diametrically opposed to economic
      truth, i.e. the community's interests, due to the high cost of screening. How can
      screening be envisaged for the future? In families with no particular risk,
      screening should be clinical, but will probably start earlier and will continue
      later, because of the improvement of diagnostic tools and prolongation of life
      expectancy. In high-risk families, the development of genetic tests will be able
      to determine whether or not a man has inherited predisposition genes. If he has
      inherited these genes, he will then be submitted to particularly early,
      meticulous and repeated screening.

PMID- 9599634
TI  - [Prostatic specific antigen in practice in 1997].
AB  - PSA (Prostate Specific Antigen) has modified the management of prostatic disease.
      Changes of PSA levels can be observed in many clinical circumstances other than
      cancer (endoscopic procedures, prostatitis, medications, etc.). Various methods
      have been proposed to increase the specificity of PSA in prostatic cancer,
      particularly when the PSA level is between 4 and 10 ng/ml: age-related PSA, PSA
      density, PSA velocity, freePSA. These methods allow more refined indications for
      transrectal biopsies of the prostate which provide the histological evidence
      essential for the diagnosis of cancer.

PMID- 9599635
TI  - [Benign prostatic hypertrophy: mini-invasive treatments (interstitial laser
      transurethral needle ablation-thermotherapy)].
AB  - Endoscopic resection is the "gold standard" to treat benign prostatic hyperplasia
      refractory to medical treatments, because it is effective and only relatively
      aggressive. In young patients or debilitated elderly patients, there is a place
      for so-called minimally invasive surgical treatments, consisting of three
      possibilities: interstitial laser, TUNA (transurethral needle ablation), and
      thermotherapy. The results of these last two techniques are very similar o those
      obtained by endoscopic resection, with virtually no complications. These
      treatments are performed on an outpatient basis and have no consequences for
      sexuality. Thermotherapy has also been approved by the FDA in the USA. In France,
      these treatments can only be used in the context of a clinical trial.

PMID- 9599636
TI  - [Treatment for impotence].
AB  - For the treatment of erectile dysfunction, the authors recommend that prostheses
      be reserved for cases refractory to all other treatments. Local treatments by
      injection of erectogenic substances consist of paraverine and prostaglandin E1. A
      new oral treatment is also available, not with yohimbine or apomorphine, but with
      sildenafil (viagra).

PMID- 9599637
TI  - [Survival and quality of life of patients with testicular cancer].
AB  - Cisplatin has revolutionized the prognosis of testicular cancers. Stage I non
      seminomatous germ cell tumours can be cured in 98% of cases; adjuvant therapy,
      chemotherapy or lymph node dissection, is recommended in high-risk tumours, while
      surveillance is indicated in tumours with a low risk of recurrence. Good
      prognosis metastatic non-seminomatous germ cell tumours are cured in almost 80%
      of cases at the cost of well tolerated chemotherapy, 3 BEP or 4 EP. The morbidity
      of lymph node dissection has been markedly decreased by means of various
      techniques of preservation of all or part of the sympathetic and lumbar
      contingent. Resection of residual masses after chemotherapy for metastatic non
      seminomatous germ cell tumours is still recommended in the majority of cases.
      Stage I seminomatous germ cell tumours are cured in 98% of cases by 25 Grays of
      lumbo-aortic radiotherapy. Screening for carcinoma in situ in the contralateral
      testis to the primary tumour is controversial, but is recommended in the case of
      lowering of a maldesended testis after the age of puberty. Future paternity is a
      major concern in tumours of young adults, most of which are cured.

PMID- 9599638
TI  - [Female urinary incontinence. Which assessments? Which treatment?].
AB  - Urinary incontinence, corresponding to the definition of involuntary urine leaks,
      due to alteration of the physiological mechanisms of continence, experienced as
      discomfort in everyday life affects approximately 10% of the female population.
      The main predisposing factors are age, child-birth (particularly the first),
      recurrent urinary tract infections, and obesity. Pathophysiologically, urine leak
      occurs when the forces of expulsion resulting from abdominal straining or
      detrusor contraction, exceed the physiological (urethral sphincter device) and
      pathological (obstruction) continence forces. These two mechanisms correspond to
      two types of incontinence, stress and urge incontinence, which are primarily
      diagnosed on the basis of the clinical interview, which must also strive to
      evaluate the volume of urine leaks, the circumstances inducing incontinence, and
      associated urinary symptoms such as dysuria and frequency. Clinical examination,
      in women in the gynaecological position, demonstrates incontinence on coughing
      and control of incontinence by supporting the bladder neck (Bonney's manoeuvre);
      it also evaluates vulval trophicity and the quality of perineal musculature; it
      analyses the components of possible vaginal prolapse. The objective of
      complementary investigations is not to confirm the data of the clinical interview
      and clinical examination, but to complete them by providing additional elements.
      Radiological examinations have largely been replaced by urodynamic examinations,
      able to detect detrusor instability and evaluate the quality of sphincter tone,
      which largely determines the success of surgery. Surgery remains the reference
      treatment for stress incontinence with a success rate of almost 90%; the main
      mechanism consists of supporting the bladder neck, allowing it to close during
      efforts increasing the abdominal pressure. Perineo-sphincter rehabilitation must
      be tried first, although its results are less lasting. Currently, the only
      effective medical treatment is anticholinergic drugs in urge incontinence.

PMID- 9599639
TI  - [Urogenital tuberculosis. 80 cases].
AB  - Urogenital tuberculosis raises major diagnostic problems due to the frequently
      atypical and misleading clinical features. It is a serious disease as the lesions
      are often multifocal and extensive, requiring major surgical resection and
      urinary tract reconstruction. Prevention of this disease is based on
      generalization of BCG immunization and adequate treatment of pulmonary
      tuberculosis. Between 1985 and 1995, 80 patients with urogenital tuberculosis
      were treated in our department. These patients consisted of 50 males (62.5%) and
      30 females (37.5%) with a mean age of 38 years (range: 20 to 50 years). IVU
      revealed silent kidney in 26% of cases, ureterohydronephrosis in 36% of cases,
      small bladder in 17% of cases, and was normal in only 5% of cases. Renal function
      was impaired in 32% of patients. The diagnosis was confirmed by a positive test
      for AFB in the urine in 64% of cases, bladder biopsy in 20% of cases and
      pathological examination of the operative specimen in 20% of cases. Treatment
      consisted of temporary urinary diversion (32%), antituberculous chemotherapy in
      all patients, and corticosteroid therapy in 8.7% of patients. Surgical treatment
      was required in 95% of patients: partial nephrectomy (2.5%), nephrectomy (50%),
      enterocystoplasty (18%), ileoureteroplasty (5%), ureteric reimplantation (12.5%),
      ureterocaliceal anastomosis (1.2%).

PMID- 9599641
TI  - [Internal urethrotomy in the treatment of urethral stenoses (longterm results)].
AB  - The authors report their experience of a series of 100 patients undergoing
      internal urethrotomy for urethral stricture, with a follow-up ranging from 12
      months to 5 years. The morbidity was 16%. A satisfactory result was obtained in
      54% of cases. The site and aetiology of the stricture did not influence the
      results. Better results were obtained in shorter, isolated strictures. Poor
      results were reported in cases with extensive stricture or in patients with a
      history of urethral surgery. These cases underwent repeated urethrotomy with less
      favourable results.

PMID- 9599640
TI  - [Ureterosigmoidostomies. 35 cases].
AB  - 35 patients underwent ureterosigmoidostomy between 1986 and 1996, corresponding
      to 25 males (71%) and 10 females (29%) with a mean age of 48 years (range: 21 to
      81 years). 25 (71%) of these patients had invasive bladder cancer, 4 (12%) had a
      vesicovaginal fistula, 3 (9%) had bladder exstrophy and 3 (9%) had urethral
      trauma. All patients had normal renal function. In 2 patients, the ureter was
      dilated and in 3 other patients, one kidney was silent. The postoperative course
      are marked by death in 2 cases (6%) due to myocardial infarction, mechanical
      obstruction in 2 cases (6%), anastomotic dehiscence in 2 cases (6%). The mean
      follow-up was 4 years (range: 2 to 10 years). Eight patients (22%) developed
      impaired renal function, isolated hyperchloraemic acidosis was observed in 10
      cases (28%), hypokalaemia was observed in 2 cases (6%), and episodes of acute
      pyelonephritis were reported in 4 cases (11%). Radiological signs of upper
      urinary tract deterioration were observed in 6 cases (17%). A tumour of the
      sigmoid colon was observed in one case after a follow-up of 10 years. 25 patients
      (72%) remain dry throughout the night, while 8 (22%) need to empty their rectum
      during the night. The poorly tolerated Coffey diversion was replaced in 6
      patients (17%). The objective of this study is to analyse the results of
      ureterosigmoidostomy and to emphasize the advantages and disadvantages of this
      urinary diversion technique.

PMID- 9599642
TI  - [Priapism in adults. 16 cases].
AB  - Priapism is a rare disease, characterized by prolonged, painful and irreducible
      erection, not resulting in ejaculation. It is an andrological emergency with a
      poor prognosis, as the risk of impotence is 50% despite appropriate management.
      Treatment is essentially surgical. The authors report their experience of 16
      cases of priapism observed over a 15-year period. The mean age of the patients
      was 36 years (range: 21 to 56 years). The diagnosis was clinical. The mean time
      to consultation was 8 days (range: 1-28 days). Priapism was secondary to
      neuroleptics in 6 cases (37%), chronic myeloid leukaemia in 2 cases, sickle-cell
      anaemia in one case, radiotherapy in 1 case and the cause remained unknown in 6
      cases (37%). Treatment was surgical in every case and consisted of
      spongiocavernous anastomosis in 11 patients (Winter's procedure in 1 case, Al
      Ghorab's procedure in 6 cases and transperineal in 4 cases, with saphenocavernous
      anastomosis in 5 cases). The overall failure rate of surgical treatment was 37%.
      The success rate of spongiocavernous fistula was 70% and the authors preferred
      the Al-Ghorab type of spongiocavernous fistula.

PMID- 9599643
TI  - [Paratesticular rhabdomyosarcoma. A case report].
AB  - The authors report a case of paratesticular rhabdomyosarcoma in a 21-year-old
      patient. The clinical features were dominated by left loin pain, inguinoscrotal
      pain and scrotal swelling. Transillumination was negative. Laboratory markers
      (alpha-foetoprotein, beta HCG) were normal. Testicular ultrasound showed an
      enlarged testis, comprising heterogeneous nodules with infiltration of the
      spermatic cord. Abdominal ultrasonography and CT scan showed a latero-aortic
      retroperitoneal lymph node mass and a large left kidney. Chest x-ray was normal.
      Treatment consisted of radical orchidectomy. Histological examination of the
      operative specimen confirmed the diagnosis of paratesticular rhabdomyosarcoma.
      The patient was treated by chemotherapy and subsequently developed recurrence
      with metastases.

PMID- 9599644
TI  - Application of fluorescence in situ hybridization to the identification of
      different marker chromosomes.
AB  - Chromosome studies performed on lymphocyte culture of a baby with specific
      dysmorphism and congenital anomalies suggestive of trisomy 21 revealed a
      mosaicism: 46,XY,rea(21q21q) [25]/47,XY,rea(21q21q),+mar1[25]. The karyotype of
      the mother is normal, but the father's karyotype presents an supernumerary
      chromosome greater and different from the marker of his son: 47,XY,+mar2 (100%).
      The identification of the two marker chromosomes by standard cytogenetic
      techniques followed by molecular techniques is essential for the identification
      of the origin of these two chromosomes. The unusual presence of two different
      markers one in the father and one in the son, as well as the clinical features of
      the child, are presented. The possible role of the paternal marker, in the de
      novo chromosomal rearrangement in his child will be discussed.

PMID- 9599645
TI  - A gene for non-specific X-linked mental retardation (MRX55) is located in Xp11.
AB  - A new family with a non-specific X-linked mental retardation (MRX55) is
      described. An X-linked recessive inheritance is suggested by the segregation from
      two healthy transmitting females of moderate mental retardation in three males,
      without any specific clinical, radiological or biological features. Two point
      linkage analysis demonstrated significant linkage between the disorder and
      several markers in Xp11 (Zmax = 2.11, theta = 0); multipoint linkage analyses
      confirmed the significant linkage with a maximum lod score (Z = 2.11 at theta =
      0, at DXS8012). Recombination events observed with the flanking markers DXS1068
      and DXS1275 delineate a 34 centimorgan interval in the pericentromeric region.
      The interval of assignment pointed out in this family overlaps with several MRX
      loci previously reported in Xp11 which are reviewed here in.

PMID- 9599646
TI  - Interstitial deletion del(3)(p12p21) in a malformed child subsequent to paternal
      paracentric insertion (or intraarm shift) 46,XY, ins(3)(p24.1p12.1p21.31).
AB  - We report on a malformed stillborn with deletion 3p subsequent to direct
      paracentric insertion (intraarm shift) in the normal father which had been first
      mistaken for paracentric inversion. The corrected diagnosis was supported by FISH
      of mapped markers on metaphase chromosomes. In addition we looked for
      recombinants in sperm. This observation reminds similar cases that had been
      considered exceptions to the expected meiotic recombination of paracentric
      inversions and points to a cytogenetic pitfall. Published deletions and
      paracentric inversions in 3p are briefly quoted.

PMID- 9599647
TI  - Unusual de novo t(13;15)(q12.1;p13) translocation leading to complex mosaicism
      including jumping translocation.
AB  - We report on a patient with neurosensory deafness, cataract and moderate mental
      retardation showing a constitutional mosaicism with the predominant cell line
      consisting of a 45,XY,-13,-15,+t(13;15) translocation of the Robertsonian type.
      By means of fluorescence in situ hybridization (FISH) using a panel of
      acrocentric pericentromeric probes and various banding techniques, the
      breakpoints in the translocation were determined at 13q12.1 and 15p13
      respectively. Five other cell lines were present, at low percentage, one of them
      showing a t(13;15) tandem translocation. Interstitial telomeric sequences could
      be detected at the translocation fusion sites in both the Robertsonian and tandem
      translocations. The mosaicism appears therefore to be a consequence of
      chromosomal instability involving the t(13;15) fusion region of the predominant
      cell line, and related to the presence of interstitial telomeric sequences. The
      present observation suggests that in the pericentromeric 13q12 region, a gene
      involved in neurosensory deafness may be located.

PMID- 9599648
TI  - Impact of routine fetal ultrasonographic screening on the prevalence of Down
      syndrome in non aged mothers.
AB  - In many countries the introduction of screening programs based on maternal serum
      has reduced the number of Down syndrome. In France routine maternal serum
      screening was not available whereas ultrasound scanning during pregnancy is
      routine practice in private offices and in hospitals using high-resolution real
      time scanners and there are no legal upper limits on gestational age at
      termination of pregnancy for fetal abnormality. The objective of this study was
      to determine the impact of routine fetal ultrasonographic screening on birth
      prevalence of Down syndrome in non aged mothers. Total prevalence of Down
      syndrome during 1989 to 1996 was stable 1.43 per 1,000 with no upward or downward
      trend. The total number of liveborn Down syndrome during this period was higher
      than previously due to a changing pattern of risk in relation to maternal age.
      All women who delivered an infant with Down syndrome had had routine
      ultrasonography, including 88% in the second trimester. Out of the 154 Down
      syndrome fetuses examined, 38 had been found to have an anomaly. This low
      sensitivity (24.7%) is not the result of the quality of the ultrasound equipment.
      It may be explained by the inadequate routine, first level ultrasonographic
      examination. This study demonstrated that other screening methods than routine
      fetal ultrasonographic examination are needed in our region.

PMID- 9599649
TI  - An abnormal distribution of delta F508 genotypes in cystic fibrosis patient
      registries.
AB  - Delta F508 mutation of the CFTR gene is the most frequent deleterious allele
      involved in cystic fibrosis (CF). We have studied the distribution of the three
      genotypes, delta F508/delta F508, delta F508/x, x/x, in the American, Canadian
      and French data registries concerning CF; "x" represents the non-delta F508
      mutations. In the three registries the observed distribution of the three
      genotypes differs from the expected one, calculated according to the Hardy and
      Weinberg equilibrium. Three factors could explain this discrepancy: Wahlund's
      effect, misinterpretation of the molecular diagnosis, or an ascertainment bias in
      relation with the severity of the disease. This last factor is the most likely.

PMID- 9599650
TI  - Molecular genetics of von Willebrand disease.
AB  - Von Willebrand disease (vWD), the most common congenital bleeding disorder in
      man, is related to quantitative and/or qualitative abnormalities of von
      Willebrand factor (vWF). This multimeric glycoprotein serves as carrier protein
      of factor VIII, an essential cofactor of coagulation in plasma, and promotes
      platelet adhesion to the damaged vessel and platelet aggregation. Distinct
      abnormalities of vWF are responsible for the three types of vWD. Types 1 and 3
      are characterized by a quantitative defect of vWF whereas type 2, comprising
      subtypes 2A, 2B, 2M and 2N, refers to molecular variants with a qualitative
      defect of vWF. The knowledge of the structure of the vWF gene and the use of
      Polymerase Chain Reaction (PCR) have led to the identification of the molecular
      basis of vWD in a significant number of patients. Type 2A is characterized by a
      decreased platelet-dependent function of vWF associated with the absence of high
      molecular weight (HMW) multimers of vWF. Most of the type 2A mutations have been
      identified in the A2 domain of vWF which contains a proteolytic site, while a few
      others have been found within the propeptide and the C-terminal part of vWF which
      are involved in its multimerization and dimerization, respectively. In type 2B,
      defined by an increased affinity of vWF to platelet glycoprotein Ib (GPIb),
      various amino-acid (aa) substitutions or insertion have been localized within the
      A1 domain containing the GPIb binding site. In the latter domain have been also
      identified the few molecular abnormalities described in type 2M which is defined
      by a decreased platelet-dependent function not caused by the absence of HMW
      multimers. In type 2N, characterized by a defective binding of vWF to factor
      VIII, several aa substitutions have been identified within the factor VIII
      binding domain in the N-terminal part of vWF. The identification of gene defects
      remains difficult in types 1 and 3. Whereas various abnormalities (total, partial
      or point deletions, point insertions, nonsense mutations) have already been
      identified in type 3, the molecular basis of type 1 is still unresolved in most
      cases. The characterization of the molecular basis of vWD is of fundamental
      interest in providing further insight into the structure-function relationship
      and the biosynthesis of vWF.

PMID- 9599651
TI  - Study of Down syndrome in 238,942 consecutive births.
AB  - The genetics and the epidemiology of Down syndrome (DS) was studied in the area
      which is covered by our registry of congenital malformations. For each of the 398
      new DS cases which were ascertained during the period 1979 to 1996 more than 50
      factors were studied and compared to those from control infants. The prevalence
      of DS was 1.66 per 1000; 2.2% of the DS cases were stillbirths and 29.4% were
      induced abortions. Karyotypes were obtained in 391 cases of which all but 23 were
      47,+21;9 were mosaics (2.3%), and 14 had translocations (3.6%). Interchromosomal
      effect was a question in 7 cases. The most common types of associated
      malformations were cardiac anomalies (46.2%) and intestinal atresias (6.0%).
      Seasonality or time/space clusters were not observed in spite of the Chernobyl
      nuclear accident. No paternal age effect was demonstrated; 5.3% of the mothers of
      DS had 2 previous spontaneous abortions (controls 3.7% p < 0.05). At birth, the
      DS infants measured and weighted less and their head circumference was lower than
      in control infants. Weight of placenta was also lower than in control infants. In
      this material there were 4.5% of consanguineous marriages (P < 0.01). The
      pregnancies of the DS children were more often complicated by threatened
      abortions than in the controls, 3.2% of the mothers of the DS children were
      diabetic controls (1.7%), although the difference was not statistically
      significant. For all other factors studied no statistically significant
      difference with respect to controls could be demonstrated.

PMID- 9599652
TI  - Trisomy (12p) with telocentric and pseudoisodicentric chromosome formation in a
      fetus.
AB  - We report an 18-week-old fetus with at 47, XY, -12, +12q, +psu idic(12p)
      karyotype, mild dysmorphic features and absence of the brachiocephalic truncus.

PMID- 9599653
TI  - Comparative genomic hybridization: technical development and cytogenetic aspects
      for routine use in clinical laboratories.
AB  - Comparative genomic hybridization (CGH) offers a new global approach for
      detection of chromosomal material imbalances of the entire genome in a single
      experiment without cell culture. In this paper, we discuss the technical
      development and the cytogenetic aspects of CGH in a clinical laboratory. Based
      only on the visual inspection of CGH metaphase spreads, the correct
      identification of numerical and structural anomalies are reported. No commercial
      image analysis software was required in these experiments. We have demonstrated
      that this new technology can be set up easily for routine use in a clinical
      cytogenetics laboratory.

PMID- 9599654
TI  - Compound heterozygotes for a CF mutation and the 5T splice variant associated
      with variable presentations in a French family.

PMID- 9599655
TI  - The brain in evolution and involution.
AB  - This paper provides an overview of the phylogenetic evolution and structural
      organization of the basal ganglia. These large subcortical structures that form
      the core of the cerebral hemispheres directly participate in the control of
      psychomotor behavior. Neuroanatomical methods combined with transmitter
      localization procedures were used to study the chemical organization of the
      forebrain in each major group of vertebrates. The various components of the basal
      ganglia appear well developed in amniote vertebrates, but remain rudimentary in
      anamniote vertebrates. For example, a typical substantia nigra composed of
      numerous dopaminergic neurons that project to the striatum already exists in the
      brain of reptiles. Other studies in mammals show that glutamatergic cortical
      inputs establish distinct functional territories within the basal ganglia, and
      that neurons in each of these territories act upon other brain neuronal systems
      principally via a GABAergic disinhibitory output mechanism. The functional status
      of the various basal ganglia chemospecific systems was examined in animal models
      of neurodegenerative diseases, as well as in postmortem material from Parkinson's
      and Huntington's disease patients. The neurodegenerative processes at play in
      such conditions specifically target the most phylogenetically ancient components
      of the brain, including the substantia nigra and the striatum, and the marked
      involution of these brain structures is accompanied by severe motor and cognitive
      deficits. Studies of neural mechanisms involved in these akinetic and
      hyperkinetic disorders have led to a complete reevaluation of the current model
      of the functional organization of the basal ganglia in both health and disease.

PMID- 9599656
TI  - Fibroblast growth factors and their receptors.
AB  - Fibroblast growth factors (FGFs) represent a group of polypeptide mitogens
      eliciting a wide variety of responses depending upon the target cell type. The
      knowledge of the cell surface receptors mediating the effects of FGFs has
      recently expanded remarkably. The complexity of the FGF family and the FGF
      induced responses is reflected in the diversity and redundancy of the FGF
      receptors. In this review, a number of biochemical characteristics and biological
      properties of the FGF family and its receptors are described and their expression
      both in normal tissues and in tumours is discussed. Finally we speculate on the
      targetting of growth inhibition agents to tumours through FGF receptors.

PMID- 9599657
TI  - Chitosanase from Streptomyces sp. strain N174: a comparative review of its
      structure and function.
AB  - Novel information on the structure and function of chitosanase, which hydrolyzes
      the beta-1,4-glycosidic linkage of chitosan, has accumulated in recent years. The
      cloning of the chitosanase gene from Streptomyces sp. strain N174 and the
      establishment of an efficient expression system using Streptomyces lividans TK24
      have contributed to these advances. Amino acid sequence comparisons of the
      chitosanases that have been sequenced to date revealed a significant homology in
      the N-terminal module. From energy minimization based on the X-ray crystal
      structure of Streptomyces sp. strain N174 chitosanase, the substrate binding
      cleft of this enzyme was estimated to be composed of six monosaccharide binding
      subsites. The hydrolytic reaction takes place at the center of the binding cleft
      with an inverting mechanism. Site-directed mutagenesis of the carboxylic amino
      acid residues that are conserved revealed that Glu-22 and Asp-40 are the
      catalytic residues. The tryptophan residues in the chitosanase do not participate
      directly in the substrate binding but stabilize the protein structure by
      interacting with hydrophobic and carboxylic side chains of the other amino acid
      residues. Structural and functional similarities were found between chitosanase,
      barley chitinase, bacteriophage T4 lysozyme, and goose egg white lysozyme, even
      though these proteins share no sequence similarities. This information can be
      helpful for the design of new chitinolytic enzymes that can be applied to
      carbohydrate engineering, biological control of phytopathogens, and other fields
      including chitinous polysaccharide degradation.

PMID- 9599658
TI  - Markers of cell polarity during and after nitrogen starvation in
      Schizosaccharomyces pombe.
AB  - In Schizosaccharomyces pombe, nitrogen starvation induces transient acceleration
      of cell division and reduction in cell size with a final arrest in G1. The
      division size control appears to be impaired by mutations in cdr1/nim1 and cdr2,
      genes that encode protein kinases mediating nutritional control over the mitotic
      cycle. cdr- cells arrest after fewer rounds of division and are larger than the
      wild type. Recent work suggests that long-term nitrogen starvation causes S.
      pombe wild-type cells to become spherical, which suggests loss of cell polarity.
      cdr mutants retain the elongated shape, indicating a potential difference in cell
      polarity control relative to the wild type. We examined several markers related
      to maintenance of cell polarity in S. pombe following nitrogen starvation
      including cell division scar pattern and actin and microtubule cytoskeleton. Wild
      type cells as well as cdr mutants maintained a normal cell division scar pattern
      throughout nitrogen starvation but cells dividing under these conditions
      developed a wall malformation in the center of the septum. In cells arrested by
      nitrogen starvation, actin patches, normally associated with sites of cell wall
      deposition, were larger and distributed randomly along the cell surface.
      Cytoplasmic arrays of microtubules, which are thought to be involved in control
      of the polarity signal, were not visibly affected. The effects were similar in
      wild-type cells and in cdr- mutants. Upon refeeding, the new growth always
      reoccurred at the tip zones and there were only small deviations of its direction
      from the original axis. The results indicate that cell polarity is preserved both
      in wild-type cells, which arrest in G1 and appear spherical, and in cdr1/nim1 and
      cdr2 mutants, which arrest in G2 and appear polarized throughout the starvation
      period.

PMID- 9599659
TI  - Chemical modifications of Bacillus subtilis tryptophanyl-tRNA synthetase.
AB  - A concerted conformational change in Bacillus subtilis tryptophanyl-tRNA
      synthetase (TrpRS) was evident from previous fluorescence on the quenching of the
      single Trp residue Trp-92 in the 4FTrp-AMP complexed enzyme. In this study,
      chemical modifications of the B. subtilis TrpRS were employed to further
      characterize this conformational change, with the single Trp residue serving as a
      marker for monitoring the change. Modifications of the enzyme by means of the Trp
      specific agent N-bromosuccinimide (NBS) or 3-bromo-3-methyl-2-(2
      nitrophenylmercapto)-3H-indole (BNPS-skatole) inactivated the enzyme in accord
      with the essential role of Trp-92, as identified previously by site-directed
      mutagenesis. ATP sensitized TrpRS toward inactivation by NBS and BNPS-skatole,
      which suggested a conformational change that resulted in greater accessibility of
      Trp-92 toward modifications. In contrast, the cognate tRNATrp substrate exerted a
      specific protective effect against inactivation by both of the reagents,
      indicating that the TrpRS-tRNATrp interaction reduces the accessibility of Trp-92
      under our experimental conditions. By comparison, modification of sulfhydryl
      groups by means of iodoacetamide did not reduce TrpRS activity. Observations on
      Trp-specific modification and substrate protection effects are discussed in the
      context of the Bacillus stearothermophilus TrpRS crystal structure.

PMID- 9599660
TI  - Comparative protection against oxyradicals by three flavonoids on cultured
      endothelial cells.
AB  - Oxygen-derived free radicals are known to injure the endothelium of aorta in
      diverse disorders. In this study we compared the cytoprotective effects of three
      flavonoids against oxyradical damage to porcine aortic endothelial cells in
      vitro. Cultured porcine aortic endothelial cells were exposed to oxyradicals
      generated by xanthine oxidase--hypoxanthine (XO-HP). The cytoprotective
      activities of morin, quercetin, and catechin on these systems were compared using
      established morphologic criteria. The results in the XO-HP system showed that
      morin at 0.125, 0.25, and 0.5 mM delayed cell necrosis to 27.4 +/- 1.3, 46.8 +/-
      1.8, and longer than 70 min, respectively, compared with 12.0 +/- 1.3 min in the
      control group. These degrees of protection were significantly stronger than those
      provided by quercetin and catechin at corresponding concentrations (p < 0.01).
      Morin and quercetin were moderate inhibitors of xanthine oxidase on the basis of
      the oxygen consumption rate, whereas catechin at the same concentrations had
      little inhibitory effect. The data from uric acid formation and cytochrome c
      reduction were consistent with the oxygen consumption measurement for the three
      flavonoids.

PMID- 9599661
TI  - Purification of intact nuclear lamina and identification of novel laminlike
      proteins in Raji, a cell line devoid of lamins A and C.
AB  - Research on the structure of the nuclear lamina and the nuclear matrix of cells
      devoid of lamins A and C has been hampered by the fact that intact residual
      nuclear structures are difficult to isolate from such cells. In this paper, we
      show that some extraction parameters, such as buffer composition and the nature
      of the detergent used to remove nuclear membranes, are critical for achieving
      isolation of whole nuclear residual structures from the lymphoblastic cell line
      Raji, used as a model for cells without lamins A and C. Electron microscopic
      analysis shows that the nuclear lamina of Raji cells is formed by a network of
      intermediate-size filaments interrupted with circular discontinuities. Both
      lamins B1 and B2, and lamin D/E, are present in this structure. In addition, a
      group of 45-kDa proteins or intermediate filament protein--reacting proteins (IFA
      RPs), located uniquely in the lamina, were found to exhibit the same
      immunological and chemical characteristics as lamins. Although they behave like
      nuclear lamins, microsequencing analysis of the IFA-RPs has revealed no homology
      with known lamins. These IFA-RPs may contribute to the formation of the nuclear
      lamina filament network in the absence of lamins A and C.

PMID- 9599662
TI  - Molecular cloning of chicken calcyclin (S100A6) and identification of putative
      isoforms.
AB  - A full-length cDNA encoding smooth muscle calcyclin (S100A6) was cloned from
      chicken gizzard, using reverse transcription--polymerase chain reaction
      techniques. The deduced amino acid sequence contains 92 residues with 12
      substitutions and a 2 amino acid C-terminal extension when compared with human
      calcyclin. Calcyclin was purified from chicken gizzard by Ca(2+)-dependent
      hydrophobic chromatography, heat treatment, and anion-exchange chromatography, N
      terminal sequencing of two CNBr peptides confirmed its identity as calcyclin. Two
      isoforms of calcyclin (A and B), which differ with respect to the presence or
      absence of a C-terminal lysine, were identified and the native protein was shown
      to exist as noncovalently associated homodimers (AA and BB) and heterodimers
      (AB). Incubation of purified calcyclin AA with an extract of chicken gizzard did
      not result in degradation of calcyclin A or appearance of calcyclin B, suggesting
      that calcyclin B is a bona fide isoform rather than a proteolytic fragment
      generated during purification. Western blotting of chicken tissues with anti
      (gizzard calcyclin) indicated abundant expression of calcyclin in smooth muscle
      tissues, including esophagus, large intestine, and trachea, with lower levels in
      lung, heart, kidney, and brain, and none detectable in liver or skeletal muscle.

PMID- 9599663
TI  - 5'-3' interactions in regulation of translation in Xenopus early embryos.
AB  - We have investigated the effects of 3' noncoding elements in enhancing
      translation of messengers having translation-inhibiting 5' untranslated regions
      (UTRs). The translation of transcripts bearing the 5' UTRs of either human c-myc
      or a synthetic hairpin structure upstream of a chloramphenicol acetyltransferase
      (CAT) reporter sequence is greatly attenuated in early embryos of Xenopus laevis.
      Translation of transcripts bearing the human c-myc-5' UTR was markedly stimulated
      by the presence of 3' poly(A). Transcripts bearing the 5' hairpin element were
      insensitive to the presence of poly(A), but they were extremely sensitive to the
      composition of the 3' UTR. A GC-rich distal sequence repressed translation,
      whereas a proximal GGAAU sequence promoted translation of these transcripts. Our
      results support the concept that long-range interactions between the 5' and 3'
      ends of transcripts are important in regulating translation in Xenopus embryos.

PMID- 9599664
TI  - Expression of retinoid X receptors and COUP-TFI in a human salivary gland
      adenocarcinoma cell line.
AB  - The growth of the adenocarcinoma cell line derived from human salivary gland
      (HSG) is regulated by all-trans-retinoic acid (t-RA), which binds to its specific
      receptor, retinoic acid receptors (RARs), located in the nucleus, and thereby
      transactivates target genes. In this study, we examined the binding
      characteristics of the nuclear extract of HSG cells to the retinoic acid response
      element (RARE) compared with those of in vitro translated RAR alpha and retinoid
      X receptor alpha (RXR alpha), a heterodimeric partner of RAR alpha. Gel shift
      analysis using anti-RAR alpha and anti-RXR alpha antibodies revealed that the
      translated RAR alpha bound to RARE as a heterodimer with RXR alpha. In contrast,
      the binding of the nuclear extract of HSG cells to RARE showed a heterogeneous
      pattern, suggesting the existence of several species of RXRs as well as RARs in
      the nuclei of HSG cells. We therefore tried to clone these putative RXRs by the
      polymerase chain reaction using degenerated oligonucleotide primers conserved
      across the RXR family. The DNA sequencing of the recombinant clones revealed the
      expression of RXR alpha and RXR beta. In addition, chicken ovalbumin upstream
      promoter-transcription factor I (COUP-TFI), which is also an RXR family member,
      was cloned. To evaluate the transcriptional activity of RARs and RXRs
      endogenously expressed in HSG cells, we performed a transient transfection
      analysis. When HSG cells were transfected with a luciferase reporter plasmid
      containing two repeats of either the RARE of the RAR beta gene or that of
      cellular retinol-binding protein II gene, positioned upstream of a thymidine
      kinase promoter fused to the luciferase sequence, a 2-3-fold induction of
      luciferase activity was observed in both cases. These results suggest that RARs
      and RXRs endogenously expressed in HSG cells were transcriptionally active in
      vivo. Thus, our findings showed that RXR alpha, RXR beta, and COUP-TFI are
      expressed in HSG cells and suggest that these molecules function as heterodimeric
      partners of RARs and (or) competitive repressors for RAREs and are involved in
      cellular responses mediated by retinoids.

PMID- 9599665
TI  - Expression of tenascin-C by human endometrial adenocarcinoma and stroma cells:
      heterogeneity of splice variants and induction by TGF-beta.
AB  - Localization of tenascin-C in vivo and cell culture experiments in vitro have
      provided evidence for stromal production of tenascin-C in malignant tumors of a
      variety of organs. Here we raised the question of whether the mesenchymal stroma
      in the case of endometrial adenocarcinoma is the unique source of tenascin-C.
      Therefore, the expression of tenascin-C mRNA by human endometrial adenocarcinoma
      cells and endometrial stroma cells was investigated. Several preparations of
      endometrial stroma cells produced tenascin-C mRNA. Using a serum-free defined
      cell culture medium, production of tenascin-C mRNA could be increased by adding
      either serum or 20 ng TGF-beta/mL to the cell culture medium. Reverse
      transcriptase polymerase chain reaction analysis revealed that five out of six
      endometrial adenocarcinoma cell lines produced tenascin-C mRNA. Northern blot
      experiments and ribonuclease protection assays provided evidence that the number
      of copies of tenascin-C mRNA was small. Analysis of expressed splice variants by
      reverse transcriptase polymerase chain reaction analysis revealed the abundance
      of one major splice variant that lacked all potential alternatively spliced
      fibronectin type-III-like repeats. Regarding larger splice variants, all fragment
      sizes that could theoretically originate from seven alternatively spliced
      fibronectin type-III-like repeats were observed. Evaluating relative signal
      intensities, the splice variants containing a single fibronectin type-III-like
      repeat and the variant possessing all but one alternatively spliced repeats were
      most frequent. In summary, evidence is provided that tenascin-C can originate
      from both tissue compartments of the human endometrium stroma and (tumor)
      epithelium. Splice variant analysis revealed a high number of splice variants and
      a relative high proportion of variants that have so far been regarded as minor
      constituents of expressed tenascin-C.

PMID- 9599666
TI  - Molecular cloning and expression of avian smooth muscle S100A11 (calgizzarin,
      S100C).
AB  - S100A11 (calgizzarin or S100C), a member of the S100 family of Ca(2+)-binding
      proteins, was first identified in chicken gizzard smooth muscle and subsequently
      detected in several mammalian species and tissues. We now report the full-length
      coding sequence of avian smooth muscle S100A11. The cloned nucleotide sequence is
      515 bases in length, which includes in-frame start and stop codons and encodes a
      protein of 101 amino acids. The chicken S100A11 sequence differs from human
      S100A11 at 25 positions (9 conserved) and is four residues shorter (overall
      identity 72.4%, similarity 81%). The protein contains two EF hand and conserved
      hydrophobic residues involved in dimer formation. Cloned avian S100A11 expressed
      in Escherichia coli and purified by Ca(2+)-dependent hydrophobic interaction
      chromatography and ion-exchange chromatography was recognized by polyclonal
      antibodies raised against tissue-purified protein and, like tissue-purified
      S100A11, bound 45Ca2+ in a gel overlay assay.

PMID- 9599667
TI  - Effect of herbimycin A on hsp30 and hsp70 heat shock protein gene expression in
      Xenopus cultured cells.
AB  - We have examined the effect of herbimycin A, a benzoquinoid ansamycin antibiotic,
      on the pattern of gene expression in amphibians. Exposure of Xenopus laevis A6
      kidney epithelial cells to 1 microgram/mL herbimycin A induced the synthesis of
      the heat shock proteins hsp30 and hsp70 as well as 33- and 45-kDa proteins.
      Enhanced synthesis of a 34-kDa protein appears to be specific to herbimycin A
      because its synthesis did not increase after heat shock (35 degrees C). In
      addition, the synthesis of hsp30 and hsp70 induced by herbimycin A was
      accompanied by an increase in their mRNAs. Herbimycin A induced a transient
      accumulation of hsp30 and hsp70 mRNA, which peaked between 4 and 6 h. Finally,
      concurrent treatment of cells with 0.5 microgram/mL herbimycin A and a mild heat
      shock of 27 degrees C yielded a synergistic accumulation of hsp30 and hsp70 mRNA.
      These studies demonstrate that herbimycin A can induce the expression of a set of
      stress proteins in amphibians and that concurrent treatment with herbimycin A and
      mild heat shock has a synergistic effect on the accumulation of hsp30 and hsp70
      mRNA.

PMID- 9599668
TI  - UV irradiation of a B-cell hybridoma increases expression of alkaline
      phosphatase: involvement in apoptosis.
AB  - Expression of alkaline phosphatase (APase) by 7TD1 B-cell hybridoma was amplified
      by ultraviolet irradiation; cell growth was inhibited and cell death by apoptosis
      was increased. Irradiation induced high levels of APase activity in cycling as
      well as in apoptotic cells. In contrast, APase activity faded with time in
      nonirradiated cells and was no longer expressed in spontaneous apoptotic cells
      appearing after several days in culture. This was demonstrated by cell
      morphology, DNA fragmentation, and flow cytometry after simultaneous staining of
      DNA with Hoechst 33342 and APase with naphthol AS-TR phosphate--fast red RC
      fluorescent reagent. Levamisole, a specific inhibitor of APase activity, almost
      totally abrogated apoptosis induced by ultraviolet irradiation at doses that
      failed to affect 7TD1 cell survival. These data suggest that APase could play a
      role in the signalling cascade that mediates apoptosis in irradiated cells.

PMID- 9599669
TI  - Characterization of stable RNAs from the resected intestinal tissues of
      individuals with either Crohn's disease or ulcerative colitis.
AB  - Circular RNAs reminiscent of viroids and the human hepatitis delta virus have
      been proposed as possible nonconventional pathogens responsible for Crohn's
      disease and ulcerative colitis, two inflammatory bowel diseases. Consequently,
      RNA was extracted from various areas of intestinal tissues from individuals with
      either Crohn's disease or ulcerative colitis as well as several appropriate
      control diseases, and analyzed by two-dimensional gel electrophoresis. No
      circular viroid-like RNAs (< 1500 nucleotides) were detected, confirming a
      previous report that was limited to the investigation of small RNAs (< 300
      nucleotides). However, three small, unusually stable, linear RNAs were shown to
      be associated to both Crohn's disease and ulcerative colitis tissues: a specific
      28S ribosomal RNA cleavage product characterized previously; a 5.8S ribosomal RNA
      conformer; and a fragment homologous to transcripts from DNA CpG islands. The two
      last RNAs were detected prior to visible morphological tissue alterations,
      suggesting that they are produced early during the inflammation and that they
      have value as molecular diagnostic tools for the inflammatory bowel diseases. The
      potential cellular mechanisms producing these RNAs and their involvement in
      inflammatory bowel disease are discussed.

PMID- 9599670
TI  - Improved purification protocol of the HSV-1 protease catalytic domain, using
      immunoaffinity.
AB  - The catalytic domain of herpes simplex virus protease was expressed in
      baculovirus-infected cells and purified in milligram quantities by ion-exchange
      and size-exclusion chromatography. The usefulness of this material was limited by
      the presence of a contaminating proteolytic activity, which caused time-dependent
      degradation of the protease. As a result we decided to explore an alternative
      approach to purification. Specific monoclonal antibodies were produced and
      evaluated by surface plasmon resonance as ligands for immunoaffinity
      chromatography. One monoclonal antibody, 6H4, was chosen for coupling to an
      affinity support, and the resulting column allowed us to obtain a pure and stable
      enzyme. Immunoaffinity chromatography of herpes simplex virus type 1 protease
      resulted in successful elimination of the contaminating protease activity.
      Moreover the immunoaffinity column permitted the isolation of stable and pure
      enzyme in a one-column procedure.

PMID- 9599671
TI  - Purification and partial characterization of peptidase-1, a sex-linked enzyme in
      Pleurodeles waltl (urodele amphibian).
AB  - Peptidase-1 is a sex-linked enzyme, which can be purified from the liver of the
      amphibian urodele Pleurodeles waltl. We estimated its apparent molecular mass as
      170 kDa by gel filtration chromatography. The enzyme is composed of two subunits
      with apparent molecular masses of 90 and 99 kDa. It is strongly inhibited by
      ethylenediaminotetraacetic acid, ethylene glycol bis(beta-aminoethyl ether)-N,N
      tetraacetic acid, and 1,10-phenanthroline, indicating that peptidase-1 is a
      metallopeptidase. Peptidase-1 has optimal activity at 55 degrees C and pH 8.5.
      This acidic enzyme displays two apparent isoelectric points, at 4.9 and 5.2, and
      is essentially located in the cytosolic subcellular fraction.

PMID- 9599672
TI  - Congenital syndromes in paediatric anaesthesia: what is important to know.
AB  - The purpose of this review is to re-evaluate our approach to the perioperative
      management of children with congenital syndromes, as a result of recent advances
      in the understanding of the role of genetic factors in the aetiology of specific
      syndrome complexes, and in accordance with current paediatric anaesthetic
      practice. Recent information elucidating the genetic basis of these syndromes
      will be examined and made relevant to paediatric anaesthetists in their emerging
      roles as perioperative physicians. Diagnostic testing and family counseling, as
      well as alterations in reactions to drugs will be considered. Finally, the
      current year of clinical practice at this hospital will be reviewed to determine
      the frequency that congenital syndromes are encountered, the most common clinical
      challenges they present, and to provide examples of the management of anaesthesia
      in selected cases. The review aims to facilitate the anaesthetist's preoperative
      assessment of a child with a congenital syndrome, suggest approaches to clinical
      anaesthetic management, and be a basis for further study of the influence of
      genetics in anaesthesia.

PMID- 9599673
TI  - Cerebral aneurysms: current anaesthetic management and future horizons.

PMID- 9599674
TI  - Myocardial protection: is there anything better than ice?

PMID- 9599675
TI  - Epidural anatomy: new observations.

PMID- 9599677
TI  - Spinal anaesthesia for outpatients: controversies and new techniques.

PMID- 9599676
TI  - Advances in regional anaesthesia and pain management.
AB  - Advances in regional anaesthesia to date have made it one of the safest
      modalities for surgical anaesthesia and pain management. Continued refinement and
      development of new block techniques and approaches enhance the potential for
      block success, rapid postoperative recovery and patient safety. This will benefit
      both patient care and the health care economy.

PMID- 9599678
TI  - Ambulatory surgery update.

PMID- 9599679
TI  - Bypassing PACU: a cost effective measure.

PMID- 9599680
TI  - New drugs in anaesthesia: can we afford them?
AB  - The most important challenge facing physicians today is the dilemma of providing
      high quality care in a fiscally responsible fashion. Cost can no longer be
      ignored. Pharmacoeconomics is a fundamental component of medical education.
      Economic issues should be an integral part of the drug development and clinical
      trials. While anaesthetists are concerned that the use of less expensive drugs
      may compromise patient outcome and satisfaction there is little evidence to
      support such concerns. This is a fertile area for intense future research.
      Pharmacoeconomics is a dynamic. The cost of drugs is not static, patterns of drug
      use shift rapidly and clinical practice is in a state of constant change. The
      answer to cost containment is not simply to cut, cap, delist or merely hope for
      the best, but rather to manage and modify practice while accommodating changing
      needs. Educational programmes, guidelines, department policies, system changes
      and financial incentives can be implemented to ensure consistent and enduring
      adherence to the principles of pharmacoeconomics and value based care. Some
      suggest that national societies should create guidelines for cost-beneficial
      practice. Others favour physician autonomy in drug selection. Changing physician
      behaviour is difficult. This change will occur gradually and will be the topic of
      many emotionally charged philosophical debates. There will be great reluctance to
      deny patients pharmacologically superior drugs based on cost alone, especially
      since drugs are such a small portion of the total costs. We must exercise caution
      to ensure that we don't become penny wise and pound foolish. Drug acquisition
      costs are only one element in a large and complex equation. Concentrating on
      acquisition drug cost may be dangerous, even naive if we fall prey to knowing the
      cost of everything but the value of nothing.

PMID- 9599681
TI  - Neuromuscular monitoring: useless, optional or mandatory?

PMID- 9599682
TI  - Intravenous infusion techniques: how to do it and why we should do it.

PMID- 9599683
TI  - Labour analgesia: what are the (new) options?

PMID- 9599684
TI  - Advances in mechanical ventilation.

PMID- 9599685
TI  - Do not resuscitate orders--managing the dilemma.
AB  - The status of DNR orders (or equivalent declarations) in patients undergoing
      surgery will continue to present considerable challenges for both healthcare
      providers and patients, or their alternate decision makers. It is essential that
      all parties understand the specifics of each DNR order, focusing not only on the
      actual content of the order or declaration but also on the context in terms of
      location, timing and circumstance. The principle of "respect for persons" should
      guide, inform and shape the approach followed with each patient. Meaningful
      dialogue and "negotiation" will be required. Make no assumptions! The "required
      reconsideration" of pre-existing DNR orders should be the basic approach
      followed. There is no single "solution" for all DNR-related issues in the peri
      operative period. What may appear obvious to the anaesthetist may be viewed
      entirely differently by the patient, or even by other members of the care giving
      team. There is no justification for either the automatic suspension or the
      automatic continuation of DNR orders in patients undergoing surgery. A patient
      specific and situation-specific approach and "solution" is required. Similar
      principles will apply in acute care settings other than the operating room. Full
      engagement by health care workers in the processes addressing these issues should
      be a personally enriching experience.

PMID- 9599686
TI  - Introduction and summary of the 13th meeting of the Scientific Group on
      Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative
      testing methodologies.
AB  - A workshop on alternative toxicological testing methodologies was convened by the
      Scientific Group on Methodologies for the Safety Evaluation of Chemicals
      (SGOMSEC) 26-31 January 1997 in Ispra, Italy, at the European Centre for the
      Validation of Alternative Methods. The purpose of the workshop was to assess the
      current status of alternative testing methodologies available to evaluate adverse
      human health and environmental effects of chemicals. Another objective of the
      workshop was to identify and recommend research needed to fill knowledge gaps
      that would lead to new test methodologies. Four work groups were established to
      address conceptual issues, acute toxicity, organ toxicity, and ecotoxicology. A
      joint workshop report was prepared for each topic and included recommendations
      for the development and use of alternative methods. Participants concluded that
      alternative methods and approaches are available that can be incorporated into
      tiered strategies for toxicological assessments. Use of these methods will reduce
      the numbers of animals required, and in some instances reduce animal pain and
      distress. It was recommended that future efforts to develop test methods should
      emphasize mechanism-based methods that can provide improved predictions of
      toxicity. Continued international cooperation was encouraged to facilitate future
      progress in the development of alternative toxicological testing methods. These
      methods will provide for improvements in human health protection, environmental
      protection, and animal welfare.

PMID- 9599687
TI  - 13th meeting of the Scientific Group on Methodologies for the Safety Evaluation
      of Chemicals (SGOMSEC): alternative testing methodologies and conceptual issues.
AB  - Substantial world-wide resources are being committed to develop improved
      toxicological testing methods that will contribute to better protection of human
      health and the environment. The development of new methods is intrinsically
      driven by new knowledge emanating from fundamental research in toxicology,
      carcinogenesis, molecular biology, biochemistry, computer sciences, and a host of
      other disciplines. Critical evaluations and strong scientific consensus are
      essential to facilitate adoption of alternative methods for use in the safety
      assessment of drugs, chemicals, and other environmental factors. Recommendations
      to hasten the development of new alternative methods included increasing emphasis
      on the development of mechanism-based methods, increasing fundamental
      toxicological research, increasing training on the use of alternative methods,
      integrating accepted alternative methods into toxicity assessment,
      internationally harmonizating chemical toxicity classification schemes, and
      increasing international cooperation to develop, validate, and gain acceptance of
      alternative methods.

PMID- 9599688
TI  - 13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation
      of Chemicals (SGOMSEC): validation and acute toxicity testing.
AB  - Scientific principles demand that before newly developed alternative methods for
      safety testing are fully embraced by the industrial or regulatory community, they
      reliably and reproducibly predict the designated toxic end point. The process
      used to determine reliability and reproducibility is termed validation, and it
      generally culminates with a highly controlled, blinded study using multiple
      chemicals and laboratories. It is imperative that the validation study is
      designed to confirm the previously established reproducibility and predictive
      power of the assay. Much has been learned recently about the practical aspects of
      validation through investigation of alternative methods for acute toxicity
      testing, i.e., those methods that assess acute systemic toxicity, skin
      irritation, and eye irritation. Although considerable progress has been made-
      many alternative tests are now commonly used in various industrial settings-
      there have been few tests that have successfully passed a complete validation.
      Some of the barriers to successful validation have been a) lack of high-quality,
      reproducible animal data; b) insufficient knowledge of the fundamental biologic
      processes involved in acute toxicity; and c) the development of truly robust in
      vitro assays that can accurately respond to materials with a wide range of
      chemical and physical characteristics. It is recommended that to progress in the
      areas of eye and skin irritation we need to expand our knowledge of toxic markers
      in humans and the biochemical basis of irritation; progress in the area of acute
      systemic toxicity will require the development of in vitro models to determine
      gastrointestinal uptake, blood-brain barrier passage, and biotransformation.

PMID- 9599689
TI  - 13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation
      of Chemicals (SGOMSEC): alternative testing methodologies for organ toxicity.
AB  - In the past decade in vitro tests have been developed that represent a range of
      anatomic structure from perfused whole organs to subcellular fractions. To assess
      the use of in vitro tests for toxicity testing, we describe and evaluate the
      current status of organotypic cultures for the major target organs of toxic
      agents. This includes liver, kidney, neural tissue, the hematopoietic system, the
      immune system, reproductive organs, and the endocrine system. The second part of
      this report reviews the application of in vitro culture systems to organ specific
      toxicity and evaluates the application of these systems both in industry for
      safety assessment and in government for regulatory purposes. Members of the
      working group (WG) felt that access to high-quality human material is essential
      for better use of in vitro organ and tissue cultures in the risk assessment
      process. Therefore, research should focus on improving culture techniques that
      will allow better preservation of human material. The WG felt that it is also
      important to develop and make available relevant reference compounds for toxicity
      assessment in each organ system, to organize and make available via the Internet
      complete in vivo toxicity data, including human data, containing dose, end
      points, and toxicokinetics. The WG also recommended that research should be
      supported to identify and to validate biological end points for target organ
      toxicity to be used in alternative toxicity testing strategies.

PMID- 9599690
TI  - 13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation
      of Chemicals (SGOMSEC): alternative testing methodologies for ecotoxicity.
AB  - There is growing public pressure to minimize the use of vertebrates in
      ecotoxicity testing; therefore, effective alternatives to toxicity tests causing
      suffering are being sought. This report discusses alternatives and differs in
      some respects from the reports of the other three groups because the primary
      concern is with harmful effects of chemicals at the level of population and above
      rather than with harmful effects upon individuals. It is concluded that progress
      toward the objective of minimizing testing that causes suffering would be served
      by the following initiatives--a clearer definition of goals and strategies when
      undertaking testing procedures; development of alternative assays, including in
      vitro test systems, that are based on new technology; development of
      nondestructive assays for vertebrates (e.g., biomarkers) that do not cause
      suffering; selection of most appropriate species, strains, and developmental
      stages for testing procedures (but no additional species for basic testing);
      better integrated and more flexible testing procedures incorporating biomarker
      responses, ecophysiological concepts, and ecological end points (progress in this
      direction depends upon expert judgment). In general, testing procedures could be
      made more realistic, taking into account problems with mixtures, and with
      volatile or insoluble chemicals.

PMID- 9599691
TI  - Mechanistic approaches and the development of alternative toxicity test methods.
AB  - A mechanism can be defined as an explanation of an observed phenomenon that
      explains the processes underlying the phenomenon in terms of events at lower
      levels of organization. A prerequisite for new, more mechanistic, approaches,
      which would use in vitro systems rather than conventional animal analogy models,
      is a strengthening of the underlying scientific basis of toxicity testing. This
      will require greater recognition of the differences between fidelity and
      discrimination models and between analogy and correlation models. The development
      of high-fidelity, high-discrimination tests with a sound mechanistic basis will
      also require greater appreciation of the interdependence of all the components of
      test systems and the development of new alternative (i.e., nonanimal) testing
      strategies that can provide the specific knowledge needed for making relevant and
      reliable predictions about the potential effects of chemicals and products in
      human beings. The optimal use of this new knowledge will require fundamental
      changes to current practices in risk assessment.

PMID- 9599692
TI  - Integration of QSAR and in vitro toxicology.
AB  - The principles of quantitative structure-activity relationships (QSAR) are based
      on the premise that the properties of a chemical are implicit in its molecular
      structure. Therefore, if a mechanistic hypothesis can be proposed linking a group
      of related chemicals with a particular toxic end point, the hypothesis can be
      used to define relevant parameters to establish a QSAR. Ways in which QSAR and in
      vitro toxicology can complement each other in development of alternatives to live
      animal experiments are described and illustrated by examples from acute
      toxicological end points. Integration of QSAR and in vitro methods is examined in
      the context of assessing mechanistic competence and improving the design of in
      vitro assays and the development of prediction models. The nature of biological
      variability is explored together with its implications for the selection of sets
      of chemicals for test development, optimization, and validation. Methods are
      described to support the use of data from in vivo tests that do not meet today's
      stringent requirements of acceptability. Integration of QSAR and in vitro methods
      into strategic approaches for the replacement, reduction, and refinement of the
      use of animals is described with examples.

PMID- 9599693
TI  - Alternative tests: carcinogenesis as an example.
AB  - Acceptance of new tests that are alternatives to currently used toxicology tests
      is a topic of considerable importance in the field of toxicology. Carcinogenicity
      testing today normally includes 2-year studies in rats and mice of both sexes,
      following widely accepted procedures for husbandry; selection of dose levels;
      pathology and toxicity observations; and statistical interpretation of tumor
      data. These studies are usually preceded by tests for genetic toxicity and
      subchronic toxicity studies to select dose levels for the 2-year studies.
      Although these data are used for quantitative risk assessment, the mechanistic
      basis for effects is usually unknown. The series of studies is very expensive and
      requires 5 years or more to conduct. Alternative approaches are being developed
      that would provide more mechanistic information and hopefully would permit
      decisions to be made about carcinogenic potential without the need to conduct 2
      year studies in rats and mice of both sexes. Decisions could be based on a
      profile of data rather than on the result of one test. Procedures for regulatory
      acceptance of new approaches for carcinogenicity testing are critical to future
      progress.

PMID- 9599694
TI  - Evaluation and validation issues in the development of transgenic mouse
      carcinogenicity bioassays.
AB  - Transgenic mouse models have emerged as plausible alternatives to long-term
      bioassays for carcinogenicity. Three transgenic lines evaluated to date have
      shown a clear capability to discriminate between carcinogens and noncarcinogens,
      using long-term bioassay results as the standard. The data also suggest that the
      transgenic lines will not fully duplicate long-term bioassay results. It is
      proposed that these models do not respond to chemicals that have induced highly
      restricted species or strain-specific tumor responses in mice or rats. Rather,
      the value of the transgenic models is predicated on a preferential response to
      transspecies carcinogens (i.e., those positive in both rats and mice, often
      including tumors in the same tissues). Thus, although results in transgenic
      models may not be completely concordant with long-term bioassays, the data can be
      used effectively in chemical and drug safety assessments. Further, it is proposed
      that validation of the models is readily achievable via ongoing studies.
      Validation of any alternative model is best achieved by sufficient mechanistic
      understanding of the model to reasonably predict the outcome of bioassays
      conducted in the models and use all available information on the drug or
      chemical. This goal can now be met with the transgenic mouse lines.

PMID- 9599695
TI  - Validation of alternative methods for toxicity testing.
AB  - Before nonanimal toxicity tests may be officially accepted by regulatory
      agencies, it is generally agreed that the validity of the new methods must be
      demonstrated in an independent, scientifically sound validation program.
      Validation has been defined as the demonstration of the reliability and relevance
      of a test method for a particular purpose. This paper provides a brief review of
      the development of the theoretical aspects of the validation process and updates
      current thinking about objectively testing the performance of an alternative
      method in a validation study. Validation of alternative methods for eye
      irritation testing is a specific example illustrating important concepts.
      Although discussion focuses on the validation of alternative methods intended to
      replace current in vivo toxicity tests, the procedures can be used to assess the
      performance of alternative methods intended for other uses.

PMID- 9599696
TI  - In vitro alternatives for ocular irritation.
AB  - The necessity of using animals to test whether new chemicals and products are eye
      irritants has been questioned with increasing frequency and fervor over the last
      20 years. During this time many new nonanimal methods have been proposed as
      reliable alternatives to the traditional rabbit (Draize) test. To date, however,
      none of these nonanimal (in vitro) tests have become universally accepted as a
      complete replacement for the Draize test. To understand why a complete
      replacement has not been found, one has to first understand the reasonably
      complex structure of the eye, the standard Draize scoring scale--which is based
      on a qualitative evaluation of three different tissues--the differences between
      human and rabbit eyes, the intrinsic variability of the animal test, and the
      details of the different in vitro tests that have been proposed as replacements.
      The in vitro tests vary from relatively simple assays using single cells to more
      sophisticated assays that use discarded animal tissue or artificially constructed
      human tissue. It is clear that appropriately designed in vitro tests will
      eventually give more useful mechanistic information about ocular injury from
      which we can more comfortably predict the risk of human eye irritation from new
      products and ingredients.

PMID- 9599697
TI  - Dermal toxicity: alternative methods for risk assessment.
AB  - Conceptually, irritant contact dermatitis (irritation) and allergic contact
      dermatitis (ACD) in man should provide the ideal platforms to launch in vitro
      toxicology into the pantheon of in vitro testing assays. In theory, irritant
      dermatitis has been considered by most a simple area of cutaneous biology,
      whereas ACD is a complex area of biology. However, both result in responses that
      are reasonably stereotypical and well characterized. The biology of the
      underlying mechanisms is becoming characterized and will thus allow development
      of mechanistically based in vitro assays that will be scientifically validated
      and thus acceptable to regulatory agencies.

PMID- 9599698
TI  - Acute oral toxicity.
AB  - The purposes of acute toxicity testing are to obtain information on the biologic
      activity of a chemical and gain insight into its mechanism of action. The
      information on acute systemic toxicity generated by the test is used in hazard
      identification and risk management in the context of production, handling, and
      use of chemicals. The LD50 value, defined as the statistically derived dose that,
      when administered in an acute toxicity test, is expected to cause death in 50% of
      the treated animals in a given period, is currently the basis for toxicologic
      classification of chemicals. For a classical LD50 study, laboratory mice and rats
      are the species typically selected. Often both sexes must be used for regulatory
      purposes. When oral administration is combined with parenteral, information on
      the bioavailability of the tested compound is obtained. The result of the
      extensive discussions on the significance of the LD50 value and the concomitant
      development of alternative procedures is that authorities today do not usually
      demand classical LD50 tests involving a large number of animals. The limit test,
      the fixed-dose procedure, the toxic class method, and the up-and-down methods all
      represent simplified alternatives using only a few animals. Efforts have also
      been made to develop in vitro systems; e.g., it has been suggested that acute
      systemic toxicity can be broken down into a number of biokinetic, cellular, and
      molecular elements, each of which can be identified and quantified in appropriate
      models. The various elements may then be used in different combinations to model
      large numbers of toxic events to predict hazard and classify compounds.

PMID- 9599699
TI  - Neurotoxicity testing: a discussion of in vitro alternatives.
AB  - A large number of chemicals may exert adverse effects on the central and/or
      peripheral nervous system. A commonly recommended strategy for neurotoxicity
      testing is that of a tiered approach aimed at identifying and characterizing the
      neurotoxicity of a compound. Guidelines exist in the United States and other
      countries that define the tests to be utilized in tier 1 testing. To address
      problems related to the increasing cost and time required for toxicity testing,
      the increasing number of chemicals being developed, and the concern of animal
      welfare activists, attention is currently being devoted to in vitro alternatives.
      This paper addresses the use of in vitro systems in neurotoxicology, and their
      potential role in a general strategy for neurotoxicity testing. The advantages
      and disadvantages of in vitro approaches for mechanistic studies and for
      screening of neurotoxicants are discussed. Suggestions for further validation
      studies are proposed.

PMID- 9599701
TI  - Target organs and systems: methodologies to assess immune system function.
AB  - Immunotoxicity encompasses both reduced and heightened immune function. Diverse
      chemicals can impair functioning of the immune system. Both monographs and books
      have been devoted to detailed descriptions of immunotoxicity. This paper gives a
      brief overview of the methods currently used to assess the immunotoxic potential
      of chemicals. It also discusses the trend toward the use of alternative methods
      to mammalian models, such as feral species, in vitro assays, and computational
      models. The strategy of using a tier approach to screen chemicals for
      immunotoxicity is described, together with the rationale for, and limitations of,
      this approach. Interpretation of data with regard to clinical disease and human
      health is addressed. The immune system poses substantial complexities in this
      regard as the system has functional reserve and functional redundancy.

PMID- 9599704
TI  - Reproduction and development.
AB  - The currently developed and validated in vitro tests for female and male
      fertility and also for developmental toxicity are described and evaluated
      according to their potential use as screening or replacement alternatives to the
      established in vivo tests in reproductive and developmental toxicology.
      Alternative methods today can only be used to evaluate a few specific components
      of the integrated reproductive functions in both females and males. However, in
      the field of developmental toxicity testing there is a strong theoretical and
      empirical basis for the predictive power of in vitro screens using mammalian
      embryos as well as embryonic cells and tissues. Several of these assays have been
      validated or are currently undergoing validation in several laboratories and are
      > 80% concordant with in vivo results. Failure to achieve 100% accuracy reflects
      the inherent limitations of these systems, which are manageable, as the
      concordance rates are still good. The level of concordance suggests that these
      assays are adequate for screening purposes to complement traditional in vivo
      testing. The use of these assays as screens will save valuable in vivo testing
      resources for those compounds most likely to enter the market and to which people
      will be exposed.

PMID- 9599700
TI  - Liver cell models in in vitro toxicology.
AB  - In vitro liver preparations are increasingly used for the study of hepatotoxicity
      of chemicals. In recent years their actual advantages and limitations have been
      better defined. The cell models, slices, and mainly primary hepatocyte cultures,
      appear to be the most powerful in vitro systems, as liver-specific functions and
      responsiveness to inducers are retained either for a few days or several weeks
      depending on culture conditions. Maintenance of phase I and phase II xenobiotic
      metabolizing enzyme activities allows various chemical investigations to be
      performed, including determination of kinetic parameters, metabolic profile,
      interspecies comparison, inhibition and induction effects, and drug-drug
      interactions. In vitro liver cell models also have various applications in
      toxicology: screening of cytotoxic and genotoxic compounds, evaluation of
      chemoprotective agents, and determination of characteristic liver lesions and
      associated biochemical mechanisms induced by toxic compounds. Extrapolation of
      the results to the in vivo situation remains a matter of debate. Presently, the
      most convincing applications of liver cell models are the studies on different
      aspects of metabolism and mechanisms of toxicity. For the future, there is a need
      for better culture conditions and differentiated hepatocyte cell lines to
      overcome the limited availability of human liver tissues. In addition, strategies
      for in vitro analysis of potentially toxic chemicals must be better defined.

PMID- 9599703
TI  - Nephrotoxicity testing in vitro--what we know and what we need to know.
AB  - The kidney is affected by many chemicals. Some of the chemicals may even
      contribute to end-stage renal disease and thus contribute considerably to health
      care costs. Because of the large functional reserve of the kidney, which masks
      signs of dysfunction, early diagnosis of renal disease is often difficult.
      Although numerous studies aimed at understanding the mechanisms underlying
      chemicals and drugs that target various renal cell types have delivered enough
      understanding for a reasonable risk assessment, there is still an urgent need to
      better understand the mechanisms leading to renal cell injury and organ
      dysfunction. The increasing use of in vitro techniques using isolated renal
      cells, nephron fragments, or cell cultures derived from specific renal cell types
      has improved our insight into the molecular mechanisms involved in
      nephrotoxicity. A short overview is given on the various in vitro systems
      currently used to clarify mechanistic aspects leading to sublethal or lethal
      injury of the functionally most important nephron epithelial cells derived from
      various species. Whereas freshly isolated cells and nephron fragments appear to
      represent a sufficient basis to study acute effects (hours) of nephrotoxins,
      e.g., on cell metabolism, primary cultures of these cells are more appropriate to
      study long-term effects. In contrast to isolated cells and fragments, however,
      primary cultures tend to first lose several of their in vivo metabolic properties
      during culture, and second to have only a limited life span (days to weeks).
      Moreover, establishing such primary cultures is a time-consuming and laborious
      procedure. For that reason many studies have been carried out on renal cell
      lines, which are easy to cultivate in large quantities and which have an
      unlimited life span. Unfortunately, none of the lines display a state of
      differentiation comparable to that of freshly isolated cells or their primary
      cultures. Most often they lack expression of key functions (e.g., gluconeogenesis
      or organic anion transport) of their in vivo correspondents. Therefore, the use
      of cell lines for assessment of nephrotoxic mechanisms will be limited to those
      functions the lines express. Upcoming molecular biology approaches such as the
      transduction of immortalizing genes into primary cultures and the utilization of
      cells from transgenic animals may in the near future result in the availability
      of highly differentiated renal cells with markedly extended life spans and near
      in vivo characteristics that may facilitate the use of renal cell culture for
      routine screening of nephrotoxins.

PMID- 9599702
TI  - Alternative testing systems for evaluating noncarcinogenic, hematologic toxicity.
AB  - Hematopoietic tissues are the targets of numerous xenobiotics. Clinical
      hematotoxicity is either a decrease or an increase in peripheral blood cell
      counts in one or more cell lineages--a cytopenia or a cytosis, respectively--that
      carries a risk of an adverse clinical event. The purpose of in vitro
      hematotoxicology is the prediction of these adverse hematologic effects from the
      effects of the toxicants on human hematopoietic targets under controlled
      experimental conditions in the laboratory. Building on its important foundations
      in experimental hematology and the wealth of hematotoxicology data found in
      experimental oncology, this field of alternative toxicology has developed rapidly
      during the past decade. Although the colony-forming unit-granulocyte/monocyte
      neutrophil progenitor is most frequently evaluated, other defined progenitors and
      stem cells as well as cell types found in the marrow stroma can be evaluated in
      vitro. End points have been proposed for predicting toxicant exposure levels at
      the maximum tolerated dose and the no observable adverse effect level for the
      neutrophil lineage, and several clinical prediction models for neutropenia have
      developed to the point that they are ready for prospective evaluation and
      validation in both preclinical species and humans. Known predictive end points
      are the key to successful comparisons across species or across chemical
      structures when in vitro dose-response curves are nonparallel. Analytical
      chemistry support is critical for accurate interpretation of in vitro data and
      for relating the in vitro pharmacodynamics to the in vivo pharmacokinetics. In
      contrast to acute neutropenia, anemia and acute thrombocytopenia, as well as
      adverse effects from chronic toxicant exposure, are much more difficult to
      predict from in vitro data. Pharmacologic principles critical for clinical
      predictions from in vitro data very likely will apply to toxicities to other
      proliferative tissues, such as mucositis.

PMID- 9599706
TI  - Correlations of Vibrio fischeri bacteria test data with bioassay data for other
      organisms.
AB  - Linear relationships of the median lethal concentrations of several hundreds of
      chemicals for a variety of organisms with Vibrio fischeri median effective
      concentrations are investigated. Significant correlations can be developed for
      many aquatic species including the fishes fathead minnow, bluegill, catfish,
      goldfish, goldorfe, guppy, killifish, rainbow trout, sheepshead minnow, and
      zebrafish; the water flea Daphnia sp.; such crustaceans as Artemia sp. and
      Crangon sp.; the ciliate Tetrahymena pyriformis; and algae, such as Chlorella sp.
      These interspecies relationships can be used to estimate order-of-magnitude type
      toxic effects of many substances for these aquatic organisms. Highly significant
      relationships can be obtained when selecting compounds on a chemical basis, such
      as alcohols, ketones, aromatics, etc., which allow the calculation of the
      compounds' toxicities to the corresponding aquatic species with increased
      accuracy and confidence. Analogous correlations with mammalian (rat and mouse)
      oral, intraperitoneal, and intravenous median lethal dose (LD50) data are much
      weaker than those for most aquatic species. However, there are significant
      differences between these three routes of administration and the intravenous LD50
      data show the best relationship with the Vibrio data.

PMID- 9599705
TI  - Identification and assessment of endocrine disruptors: limitations of in vivo and
      in vitro assays.
AB  - It has been suggested that chemicals and complex mixtures capable of modulating
      the endocrine system may contribute to adverse health, reproduction, and
      developmental effects in humans and wildlife. These effects include increased
      incidence of hormone-dependent cancers, compromised reproductive fitness, and
      abnormal reproductive system development. In response to public concern,
      regulatory agencies in North America and Europe are formulating potential
      strategies to systematically test chemicals and complex mixtures for their
      endocrine-disrupting activities. Because of the complexity of the endocrine
      system and the number of potential endocrine disruptor targets, a tiered approach
      involving a complementary battery of short- and long-term in vivo and in vitro
      assays that assesses both receptor and nonreceptor-mediated mechanisms of action
      is being considered. However, the available established assays use a limited
      number of end points, and significant information gaps exist for other potential
      targets in the endocrine system. In addition to discussing the merits and
      limitations of the assays that may be adopted, this paper also highlights
      potential problems associated with the use of a tiered testing strategy.

PMID- 9599708
TI  - Biomarker strategies to evaluate the environmental effects of chemicals.
AB  - Environmental risk assessment of chemicals depends on the production of toxicity
      data for surrogate species of mammals, birds, and fish and on making comparisons
      between these and estimated or predicted environmental concentrations of the
      chemicals. This paper gives an overview of biomarker assays and strategies that
      might be used as alternatives, that is, to replace, reduce, or refine currently
      used ecotoxicity tests that cause suffering to vertebrates. In the present
      context a biomarker is a biologic response to an environmental chemical at the
      individual level or below which demonstrates a departure from normal status. Of
      immediate interest and relevance are nondestructive assays that provide a measure
      of toxic effect in vertebrate species and that can be used in both laboratory and
      parallel field studies. A major shortcoming of this approach is that such assays
      are currently only available for a limited number of chemicals, primarily when
      the mode of action is known. Nondestructive assays can be performed on blood,
      skin, excreta, and eggs of birds, fish, reptiles, and amphibians. An interesting
      recent development is the use of vertebrate cell cultures, including transgenic
      cell lines that have been developed specifically for toxicity testing. The
      ultimate concern in ecotoxicology is the effects of chemicals at the level of
      populations and above. Current risk assessment practices do not address this
      problem. The development of biomarker strategies could be part of a movement
      toward more ecologic end points in the safety evaluation of chemicals, which
      would effect a reduction in animal tests that cause suffering.

PMID- 9599709
TI  - Dioxins and furans: epidemiologic assessment of cancer risks and other human
      health effects.

PMID- 9599707
TI  - Invertebrates in testing of environmental chemicals: are they alternatives?
AB  - An enlarged interpretation of alternatives in toxicology testing includes the
      replacement of one animal species with another, preferably a nonmammalian
      species. This paper reviews the potential of invertebrates in testing
      environmental chemicals and provides evidence of their usefulness in alternative
      testing methodologies. The first part of this review addresses the use of
      invertebrates in laboratory toxicology testing. Problems in extrapolating results
      obtained in invertebrates to those obtained from vertebrates are noted,
      suggesting that invertebrates can essentially be used in addition to rather than
      as replacements for vertebrates in laboratory toxicity tests. However, evaluation
      of the ecologic impact of environmental chemicals must include defining end
      points that may frequently differ from those classically used in biomedical
      research. In this context, alternative approaches using invertebrates may be more
      pertinent. The second part of the review therefore focuses on the use of
      invertebrates in situ to assess the environmental impact of pollutants.
      Advantages of invertebrates in ecotoxicologic investigation are presented for
      their usefulness for seeking mechanistic links between effects occurring at the
      individual level and consequences for higher levels of biologic organization
      (e.g., population and community). In the end, it is considered that replacement
      of vertebrates by invertebrates in ecotoxicity testing is likely to become a
      reality when basic knowledge of metabolic, physiologic, and developmental
      patterns in the latter will be sufficient to assess the effect of a given
      chemical through end points that could be different between invertebrates and
      vertebrates.

PMID- 9599710
TI  - The Seveso studies on early and long-term effects of dioxin exposure: a review.
AB  - The industrial accident that occurred in the town of Seveso, Italy, in 1976
      exposed a large population to substantial amounts of relatively pure 2,3,7,8
      tetrachlorodibenzo-p-dioxin. Extensive monitoring of soil levels and measurements
      of a limited number of human blood samples allowed classification of the exposed
      population into three categories, A (highest exposure), B (median exposure), and
      R (lowest exposure). Early health investigations including liver function, immune
      function, neurologic impairment, and reproductive effects yielded inconclusive
      results. Chloracne (nearly 200 cases with a definite exposure dependence) was the
      only effect established with certainty. Long-term studies were conducted using
      the large population living in the surrounding noncontaminated territory as
      reference. An excess mortality from cardiovascular and respiratory diseases was
      uncovered, possibly related to the psychosocial consequences of the accident in
      addition to the chemical contamination. An excess of diabetes cases was also
      found. Results of cancer incidence and mortality follow-up showed an increased
      occurrence of cancer of the gastrointestinal sites and of the lymphatic and
      hematopoietic tissue. Experimental and epidemiologic data as well as mechanistic
      knowledge support the hypothesis that the observed cancer excesses are associated
      with dioxin exposure. Results cannot be viewed as conclusive. The study is
      continuing in an attempt to overcome the existing limitations (few individual
      exposure data, short latency period, and small population size for certain cancer
      types) and to explore new research paths (e.g., differences in individual
      susceptibility).

PMID- 9599711
TI  - Evaluation of cardiovascular outcomes among U.S. workers exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - Some animal studies and some human studies suggest that exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) may be associated with adverse effects on the
      cardiovascular system. As part of a cross-sectional medical study comparing
      workers employed 15 years earlier in the manufacture of 2,4,5-trichlorophenol or
      one of its derivatives at two U.S. chemical plants with an unexposed comparison
      group, we examined the association between TCDD exposure and various
      cardiovascular outcomes. A total of 281 workers and 260 unexposed referents
      participated. The workers had substantial exposure to TCDD, as demonstrated by
      significantly elevated mean serum TCDD concentration of 220 pg/g of lipid,
      compared with 7 pg/g of lipid among the referents. No significant association was
      found between TCDD exposure and any of the cardiovascular outcomes including
      myocardial infarction, angina, cardiac arrhythmias, hypertension, and abnormal
      peripheral arterial flow. Although our study had sufficient statistical power to
      detect an elevated risk for cardiac arrhythmias, hypertension, and abnormal
      peripheral arterial flow, it had low power (approximately 50%) to detect an
      elevated risk for myocardial infarction and angina. Our review of the literature
      suggests that our negative findings are consistent with those from other cross
      sectional medical studies. Although several mortality studies of TCDD-exposed
      cohorts found significantly increased risks for cardiovascular disease mortality,
      similar increased risks were not observed in other mortality studies. The data
      available do not provide definitive conclusions but indicate that further
      examination of the association between TCDD exposure and cardiovascular disease
      should be pursued.

PMID- 9599712
TI  - Exposure to dioxin and nonneoplastic mortality in the expanded IARC international
      cohort study of phenoxy herbicide and chlorophenol production workers and
      sprayers.
AB  - The authors studied noncancer mortality among phenoxyacid herbicide and
      chlorophenol production workers and sprayers included in an international study
      comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to
      2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was
      discerned from job records and company questionnaires with validation by biologic
      and environmental measures. Standard mortality ratio analyses suggested a
      moderate healthy worker effect for all circulatory diseases, especially ischemic
      heart disease, among both those exposed and those not exposed to TCDD/HCD. In
      Poisson regression analyses, exposure to TCDD/HCD was not associated with
      increased mortality from cerebrovascular disease. However, an increased risk for
      circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95%
      confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53
      9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10
      to 19 years after first exposure and for those exposed for a duration of 10 to 19
      years. Mortality from suicide was comparable to that for the general population
      for all workers exposed to herbicides or chlorophenols and was associated with
      short latency and duration of exposure. More refined investigations of the
      ischemic heart disease and TCDD/HCD exposure association are warranted.

PMID- 9599713
TI  - Estimation of the cumulated exposure to polychlorinated dibenzo-p-dioxins/furans
      and standardized mortality ratio analysis of cancer mortality by dose in an
      occupationally exposed cohort.
AB  - For a cohort of 1189 male German former herbicide and insecticide workers with
      exposure to polychlorinated dibenzo-p-dioxins and -furans (PCDD/F), we report an
      extended standardized mortality ratio (SMR) analysis based on a new quantitative
      exposure index. This index characterizes the cumulative lifetime exposure by
      integrating the estimated concentration of PCDD/F at every point in time (area
      under the curve). Production department-specific dose rates were derived from
      blood levels and working histories of 275 workers by applying a first-order
      kinetic model. These dose rates were used to estimate exposure levels for all
      cohort members. Total mortality was elevated in the cohort; 413 deaths yielded an
      SMR of 1.15 (95% confidence interval [Cl] 1.05, 1.27) compared to the mortality
      of the population of Germany. Overall cancer mortality (n = 124) was
      significantly increased (SMR = 1.41, 95% Cl 1.17, 1.68). Various cancer sites
      showed significantly increased SMRs. The exposure index was used for an SMR
      analysis of total cancer mortality by dose. For 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) a significant trend (p = 0.01) for the SMRs with increasing
      cumulative PCDD/F exposure was observed. The SMR in the first exposure quartile
      (0-125.2 ng/kg x years) was 1.24 (95% Cl 0.82, 1.79), increasing to 1.73 (95% Cl
      1.21, 2.40) in the last quartile (> or = 2503.0 ng/kg x years). For all congeners
      combined as toxic equivalencies (TEQ) using international toxic equivalency
      factors, a significant increase in cancer mortality was observed in the second
      quartile (360.9-1614.4 ng/kg x years, SMR 1.64; 95% Cl 1.13, 2.29) and the fourth
      quartile (> or = 5217.7 ng/kg x years TEQ, SMR 1.64, 95% Cl 1.13, 2.29). The
      trend test was not significant. The results justify the use of this cohort for a
      quantitative risk assessment for TCDD and to a lesser extent for TEQ.

PMID- 9599714
TI  - Quantitative cancer risk assessment for dioxins using an occupational cohort.
AB  - We consider a cohort of 1189 male German factory workers (production period 1952
      1984) who produced phenoxy herbicides and were exposed to dioxins. Follow-up
      until the end of 1992 yielded a significantly increased standardized mortality
      ratio (SMR) for total cancer (SMR 141; 95% confidence interval 117-168). 2,3,7,8
      Tetrachlorodibenzo-p-dioxin (TCDD) concentrations up to 2252 ng/kg body fat were
      measured in 275 cohort members. Other higher chlorinated dioxins and furans also
      occurred in high concentrations. For quantitative analysis, the integrated TCDD
      concentration over time was used as an exposure variable, which was calculated
      using results from half-life estimation for TCDD and workplace history data. The
      other congeners were expressed as toxic equivalency (TEQ) and compared to TCDD
      using international toxic equivalency factors. Poisson and Cox regressions were
      used to investigate dose-response relationships. Various covariables (e.g.,
      exposure to beta-hexachlorocyclohexane, employment characteristics) were
      considered. In all analyses, TCDD and TEQ exposures were related to total cancer
      mortality. The power model yielded a relative risk (RR) function RR(x) = (1 +
      0.17x)0.326 for TCDD (in microgram/kilogram blood fat x years)--only a slightly
      better fit than a linear RR function--and RR(x) = (1 + 0.023x)0.795 for TEQ.
      Investigations on latency did not show strong effects. Different methods were
      applied to investigate the robustness of the results and yielded almost identical
      results. The results were used for unit risk estimation. Taking into account
      different sources of variation, an interval of 10(-3) to 10(-2) for the
      additional lifetime cancer risk under a daily intake of 1 pg TCDD/kg body
      weight/day was estimated from the dose-response models considered. Uncertainties
      regarding the dose-response function remain. These data did not indicate the
      existence of a threshold value; however, such a value cannot be excluded with any
      certainty.

PMID- 9599715
TI  - Exposure to Agent Orange and occurrence of soft-tissue sarcomas or non-Hodgkin
      lymphomas: an ongoing study in Vietnam.
AB  - Agent Orange was the most common herbicide used in the Second Indochina War in
      the course of military operations in the former South Vietnam. Agent Orange is
      contaminated by the carcinogen 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in
      mean concentrations of 2 mg/kg. After much dispute of a causal association
      between exposure to herbicides containing TCDD and occurrence of soft-tissue
      sarcoma and non-Hodgkin lymphoma, two simultaneous case-control studies were set
      up in Vietnam to examine possible relationships. Subject recruitment is ongoing,
      with target numbers of 150 cases of soft-tissue sarcoma and 150 cases of non
      Hodgkin lymphoma and diagnoses at the Cancer Center at Ho Chi Minh City, Vietnam.
      Two hospital controls are matched to each case. As in other studies of cancer in
      persons occupationally or otherwise exposed to herbicides and their contaminants,
      evaluation of past exposure of the recruited subjects is among the most
      complicated issues. Because accurate records are usually unavailable, surrogate
      measures of likely exposure are often calculated. As a first approach in our
      studies we used the Stellman and Stellman exposure index. The index is based on
      matching subjects' history of residence and the information on times and
      locations of Agent Orange spraying recorded on HERBS tape by the U.S. Army and
      taking into account the distance from the spraying as well as environmental and
      biologic half-life of TCDD. The exposure index is calculated in two centers, New
      York and Hanoi, with slightly different assumptions. In addition, samples of body
      tissues from the subjects (20 ml blood, 2 g adipose tissue, and tumor sections in
      paraffin blocks) are taken and stored. Their future analysis will provide
      additional source of exposure assessment. Strengths and weaknesses of both
      exposure measures are discussed in this paper.

PMID- 9599717
TI  - Cancer incidence in Danish phenoxy herbicide workers, 1947-1993.
AB  - A cohort study was undertaken of 2119 workers from Denmark who were potentially
      exposed to phenoxy herbicides. The workers were from two factories that produced
      phenoxy herbicides since 1947 and 1951, respectively. They had been employed
      either in the manufacture of phenoxy herbicide or in the manual service
      functions. The main product was 4-chloro-2-methylphenoxyacetic acid (MCPA). From
      1947 to 1993 the 2119 workers had a slightly lower overall cancer incidence than
      the Danish population (observed = 204; expected [Exp] = 234.23; standardized
      incidence ratio [SIR] = 0.87; 95% confidence interval [CI] 0.8-1.0). Four soft
      tissue sarcoma cases were observed (Exp = 2.47; SIR = 1.62; 95% CI = 0.4-4.1).
      All four cases occurred among men from Kemisk Vaerk Koge (Exp = 1.68; SIR = 2.38;
      95% CI = 0.7-6.1). There were six cases of non-Hodgkin's lymphoma (Exp = 5.07;
      SIR = 1.10; 95% CI = 0.4-2.6) and no significantly elevated risk of other
      cancers. Based on small numbers, the study suggests an association between the
      exposure to MCPA and related phenoxy herbicides and the risk of soft-tissue
      sarcoma. The study does not indicate a risk of non-Hodgkin's lymphoma after
      exposure to these phenoxy herbicides or a risk of other cancer diseases.

PMID- 9599716
TI  - Some aspects of the etiology of non-Hodgkin's lymphoma.
AB  - In epidemiologic studies, non-Hodgkin's lymphoma (NHL) has been associated with
      exposure to chemicals such as phenoxyacetic acids; chlorophenols; dioxins;
      organic solvents including benzene, polychlorinated biphenyls, chlordanes; and
      immunosuppressive drugs. Experimental evidence and clinical observations indicate
      that these chemicals may impair the immune system. The risk is increased for NHL
      in persons with acquired and congenital immune deficiency as well as autoimmune
      disorders. Also, certain viruses have been suggested to be of etiologic
      significance for NHL. In some cases of NHL the common mechanism for all these
      agents and conditions may be immunosuppression, possibly in combination with
      viruses.

PMID- 9599718
TI  - Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin and its congeners.
AB  - One hundred ninety-two workers in a German pesticide factory who were exposed to
      polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for
      former and present diseases and laboratory changes of the immune system.
      Moreover, in a subgroup of 29 highly exposed and 28 control persons,
      proliferation studies were performed. In addition to assays such as blood count,
      immunoglobulins, serum electrophoresis, monoclonal bands, surface markers,
      autoantibodies, and lymphocyte proliferation, two new methods, the rise of
      tetanus antibody concentration after vaccination and the in vitro resistance of
      lymphocytes to chromate, were used to diagnose the morphologic and functional
      state of the immune system. There was no stringent correlation of actual
      PCDD/PCDF concentrations with the occurrence of infections or with one of the
      immune parameters. In addition, outcomes of the tetanus vaccination and the
      chromate resistance test were not correlated with PCDD/PCDF. However, the
      chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly
      exposed persons was significantly lower than that for the control group. These
      findings indicate that the function of lymphocytes can be stressed and possibly
      impaired by high exposure to PCDD/PCDF.

PMID- 9599719
TI  - Effects of dioxins and furans on liver enzymes, lipid parameters, and thyroid
      hormones in former thermal metal recycling workers.
AB  - A cross-sectional study was performed to examine the internal exposure of
      polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDF) in
      former workers in a nonferrous metal recycling facility. Liver enzymes, lipid
      parameters, and thyroid hormones were measured to check possible biologic
      effects. Compared to background levels, the international toxicity equivalent
      levels of exposed workers were slightly elevated (median 42 ppt, range 13-281
      ppt). The workers also had higher total PCDF concentrations (median 128 ppt,
      range 30-1138 ppt). Correlation analyses demonstrate significant associations
      with only one liver enzyme, alanine aminotransferase. There were no such
      associations with serum cholesterol levels or with serum thyroid hormones.
      Because of the cross-sectional design of the study, firm conclusions cannot be
      drawn. For further evaluation, a follow-up examination appears necessary.

PMID- 9599720
TI  - Immune cell functions in industrial workers after exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin: dissociation of antigen-specific T-cell responses in
      cultures of diluted whole blood and of isolated peripheral blood mononuclear
      cells.
AB  - A comparative analysis was performed of the phenotype and function of peripheral
      blood leukocytes of two age-matched cohorts of industrial workers in chemical
      plants, one of which was exposed occupationally to high concentrations of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Median actual TCDD burdens were 116 ng/kg and
      4 ng/kg, respectively. The phenotype analysis of peripheral blood mononuclear
      cells (PBMC) revealed no significant differences in the proportions of CD3, CD4,
      or CD8+ T lymphocytes, of CD16+ natural killer cells, and of CD19+ B lymphocytes.
      However, in PBMC of the TCDD-exposed workers; the proportion of CD8+ memory T
      cells (CD45R0+) was significantly higher, and that of lymphocytes with naive
      phenotype (CD45RA+) was significantly lower than in PBMC of the control group.
      Polyclonal and antigen-specific T-cell activation was assessed in parallel in
      isolated PBMC as well as in diluted whole blood cultures. In both culture systems
      the polyclonally stimulated cytokine release did not differ significantly between
      the two cohorts; however, we found a significantly reduced interferon gamma
      release in diluted whole blood cultures but not in isolated PBMC cultures of the
      TCDD-exposed cohort when we performed an antigen-specific T-cell stimulation with
      tetanus-toxoid. Therefore, we propose that exposure of individuals to high doses
      of TCDD can partially impair in the "blood milieu" those T-cell/monocyte
      interactions that are essential for antigen-specific T-cell responses, whereas
      isolated PBMC of the same donors appear functionally less affected.

PMID- 9599721
TI  - PCDD/PCDF indoor exposure in day-care centers and PCDD/PCDF blood concentrations
      of female employees.
AB  - We determined blood concentrations of polychlorinated dibenzo-p-dioxins (PCDDs)
      and polychlorinated dibenzofurans (PCDFs) in 41 female employees with previous
      exposure to pentachlorophenol-based wood preservatives from 10 day-care centers
      in the Hamburg, Germany, area. We compared the blood concentrations with
      estimated age-dependent reference values and analyzed the correlation between
      PCDD/PCDF indoor air exposure and blood concentrations. The analyses based on the
      PCDD congeners 1,2,3,4,7,8-, 1,2,3,6,7,8-, and 1,2,3,7,8,9-hexaCDD (hexaCDD),
      1,2,3,4,6,7,8-heptaCDD (heptaCDD), octaCDD, and the 2,3,7,8-tetrachlorodibenzo-p
      dioxin toxicity equivalents calculated according to the international NATO-CCMS
      model (I-TEQ). In comparison to the estimated reference values, the blood
      concentrations of hexaCDD and I-TEQ spread around the mean estimate. Data for
      octaCDD scattered in some cases distinctly above the upper confidence limit.
      Reference values for heptaCDD could not be estimated. The correlation between
      PCDD/PCDF indoor air exposure and PCDD/PCDF blood concentrations was examined by
      linear multiple regression analysis considering different exposure variables and
      taking confounders into account. Analyses were carried out with the total study
      group and with a restricted subgroup. Associations were shown between the
      PCDD/PCDF indoor air concentrations and blood concentrations for heptaCDD and for
      the I-TEQ, whereas hexaCDD showed no association. OctaCDD showed a negative
      association in the total study group and no association in the subgroup analysis.
      In summary, the analyses showed no clear association between PCDD/PCDF indoor air
      exposure in day-care centers and PCDD/PCDF blood levels of female employees
      previously exposed to wood preservatives. By contrast, the results consistently
      indicated a positive association between PCDD/PCDF blood concentrations and
      exposure to wood preservatives in private homes.

PMID- 9599722
TI  - Occupational exposure to dioxins by thermal oxygen cutting, welding, and
      soldering of metals.
AB  - This paper focuses on one aspect of occupational dioxin exposure that is novel
      and unexpected. Exposures in excess of the German threshold limit value of 50 pg
      international toxicity equivalent (I-TEQ)/m3 are very frequent, unpredictable,
      and sometimes very high--up to 6612 pg I-TEQ/m3--during thermal oxygen cutting at
      scrap metal and demolition sites. The same procedure involving virgin steel in
      steel trade and mass production of steel objects gave no such evidence, even
      though no final conclusions can be drawn because of the low number of samples
      analyzed. Low dioxin exposures during inert gas electric arc welding confirm
      previous literature findings, whereas soldering and thermal oxygen cutting in the
      presence of polyvinyl chloride give rise to concern. The consequences of
      occupational dioxin exposure were studied by analysis of the dioxin-blood
      concentration, the body burden, of men performing thermal oxygen cutting at scrap
      metal reclamation and demolition sites, in steel trade and producing plants as
      well as for industrial welders and white-collar workers. The results concerning
      body burdens are in excellent agreement with the dioxin exposure as characterized
      by dioxin air concentration in the workplace. The significant positive
      correlation between duration and frequency of performing thermal oxygen cutting
      at metal reclamation and demolition sites expressed in job-years and dioxin body
      burden speaks for the occupational origin of the observed overload after long
      times. The results reported here lead to consequences for occupational health,
      which are discussed and require immediate attention.

PMID- 9599723
TI  - PCDD/PCDF: human background data for Germany, a 10-year experience.
AB  - This paper gives an overview of the development of the environmental or
      background exposure of humans to polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs) in Germany. To determine the background
      exposure, adipose tissue, human milk, or blood can be used. The good
      comparability of the matrices analyzed is demonstrated. The daily consumption of
      low-level contaminated food, mainly of animal origin, leads to the accumulation
      of PCDDs/PCDFs in the human adipose reservoir. The influence of factors such as
      various eating habits, severe weight loss, age, and nursing (women only) on the
      human body burden is discussed. Because of decreasing emission of PCDDs/PCDFs
      into the environment, a decline of these components in humans could be observed
      over a time span of 10 years.

PMID- 9599724
TI  - Blood lipid concentrations of dioxins and furans in a sample of BASF employees
      included in the IARC registry of workers exposed to phenoxy acid herbicides
      and/or chlorophenols.
AB  - Depending on process conditions, polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs) may be generated as low-level byproducts of
      chlorophenol and chlorophenoxy herbicides manufacture. A stratified random sample
      of 20 active employees from a cohort of phenoxy herbicide workers was selected in
      1995 for determining PCDD and PCDF congeners in blood lipids to assess the extent
      of past PCDD and PCDF exposure in this cohort and whether that exposure might
      explain site-specific cancer findings in the total cohort. This cohort is
      included in the IARC International Registry of Persons Exposed to Phenoxyacid
      Herbicides and Their Contaminants. For the 19 persons who participated, median
      PCDD and PCDF concentrations were comparable to background concentrations in the
      general population. Median levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin, the sum
      of hexachlorodibenzo-p-dioxin, pentachlorodibenzofurans, and two dioxin toxicity
      equivalents values were statistically higher in 7 employees assigned to synthesis
      operations than for 12 employees assigned to other operations. However, the PCDD
      and PCDF concentrations were low relative to those seen in other dioxin-exposed
      cohorts. We conclude that PCDD and PCDF exposures of cohort members are unlikely
      to explain the elevated standardized mortality ratios observed in this cohort for
      several cancer sites.

PMID- 9599725
TI  - A selective historical review of congener-specific human tissue measurements as
      sensitive and specific biomarkers of exposure to dioxins and related compounds.
AB  - Estimating internal exposure or dose of dioxins and related chemicals such as
      dibenzofurans and dioxinlike polychlorinated biphenyls is relatively
      straightforward in laboratory animals because a known dose is given and the
      amount absorbed can be measured. In wildlife, direct tissue measurement and
      measurement of environmental samples have both recently been used to estimate
      exposure. Until recently, human studies used only indirect indicators such as
      skin lesions to qualitatively estimate exposure to these chlorinated organic
      compounds. Environmental measurements have also sometimes been used to estimate
      human exposure. Dioxins in human tissue were not measured until the 1970s, when
      2,3,7,8-tetrachlorodibenzo-p-dioxin was measured in mothers' milk; congener
      specific measurement of dioxins and dibenzofurans in tissues (blood, milk, and
      adipose tissue) of the general population and exposed workers was first performed
      in the United States in the 1980s. Measurement in a sensitive and specific
      fashion of the 17 toxic dioxin and dibenzofuran congeners currently found in
      human tissue from industrial countries began in the 1980s. The use of known
      chemical standards, capillary columns, high resolution gas chromatography and
      mass spectrometry (GC-MS) has now become relatively common. GC-MS analysis of
      blood is currently accepted as the gold standard for estimating human exposure to
      dioxins. However, analyses are still costly and time consuming, and worldwide
      there are few qualified laboratories. There is currently a lack of knowledge
      concerning kinetics at higher and lower exposure levels for most of the toxic
      dioxin congeners and of levels in target tissues of concern.

PMID- 9599726
TI  - Estimation of occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin using
      a minimal physiologic toxicokinetic model.
AB  - In this study we investigated estimation of occupational exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) based on a minimal physiologic toxicokinetic
      model in humans. Our purpose was to obtain a mathematical tool for dose-response
      studies based on human data. We first simplified an existing model of TCDD
      kinetics in humans and estimated its parameters (i.e., liver elimination and
      background input of TCDD) using repeated measures of serum dioxin taken in
      Vietnam veterans (Ranch Hand data and data from an unexposed reference group). We
      carried out computer simulation and estimation of the model parameters both under
      a nonlinear weighted least-squares model (naive pooled data approach) and under a
      nonlinear mixed-effects model. The best parameter estimates were obtained with
      log-transformed data under a mixed-effects model: liver elimination parameter kf
      = 0.022 days-1 (95% confidence interval [CI] = 0.020, 0.024), and background
      input rate input = 0.1251 pg/kg/day (95% CI = 0.071, 0.179). The dioxin kinetic
      model and its estimated parameters were then used to provide dose estimates for a
      cohort of workers with exposure to TCDD at chemical plants in the United States.
      First, the model was used to estimate the rate of occupational intake of TCDD in
      a subset of the cohort consisting of 253 subjects for whom one measure of serum
      TCDD was available. A model of change in body-mass index over time was also
      identified for this subsample. The occupational exposure rate was estimated by
      linear regression using the above values of kinetic parameters and assuming an
      initial condition for serum TCDD of 7 ppt, i.e., the average level found in
      unexposed workers. The estimate of the occupational exposure parameter was 232.7
      pg/kg/day (95% CI 192, 273). This value can be applied to the full cohort to
      obtain for each cohort member the time course of serum dioxin concentration from
      which exposure indices can be derived. Sensitivity coefficients to model
      parameters (background input, kf, occupational exposure, and the assumed TCDD
      concentration at hire) allow for a convenient recalculation of the serum TCDD
      curve and of the derived exposure indices for different assumed values of the
      model parameters.

PMID- 9599727
TI  - An IARC evaluation of polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans as risk factors in human carcinogenesis.
AB  - The International Agency for Research on Cancer (IARC) Monographs program
      reevaluated polychlorinated dibenzo-p-dioxins and evaluated polychlorinated
      dibenzofurans as possible carcinogenic hazards to humans in February 1997, using
      the most recent epidemiologic data on exposed human populations, experimental
      carcinogenicity bioassays in laboratory animals, and supporting evidence on
      relevant mechanisms of carcinogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
      was evaluated as carcinogenic to humans (IARC group 1 classification) on the
      basis of limited evidence of carcinogenicity to humans derived from follow-up of
      workers who had been heavily exposed in industrial accidents and sufficient
      evidence of carcinogenicity in experimental animals. The evaluation also
      considered the following supporting evidence: TCDD is a multisite carcinogen in
      experimental animals and has been shown by several lines of evidence to act
      through a mechanism involving the aryl hydrocarbon receptor; this receptor is
      highly conserved in an evolutionary sense and functions the same way in humans as
      in experimental animals; tissue concentrations of TCDD are similar in heavily
      exposed human populations in which an increased overall cancer risk was observed
      and in exposed rats that developed tumors in carcinogenicity tests. Other
      polychlorinated dibenzo-p-dioxins, the nonchlorinated dibenzo-p-dioxin, and
      polychlorinated dibenzofurans were evaluated as not classifiable as to their
      carcinogenicity to humans (group 3).

PMID- 9599729
TI  - Nocturnal enuresis.
AB  - OBJECTIVE: To clarify the pathogenesis of nocturnal enuresis. METHODS: Overnight
      simultaneous monitoring of electroencephalogram and cystometrogram, developed in
      1985, was the basic method. RESULTS: Nocturnal enuresis was classified into types
      I, IIa and IIb. In type I, activation of the arousal center functioned correctly,
      but the development of the function to switch light sleep to complete awakening
      was immature. In type IIa, activation of the arousal center failed. In type IIb,
      transmission of the urinary sensation to the upper centrum was ineffective
      because of the disturbance of bladder function. CONCLUSION: There is a
      possibility that a universal concept embracing the various theories for enuresis
      proposed in the past could be obtained from this theory.

PMID- 9599730
TI  - Brainstem neural mechanisms of sleep and wakefulness.
AB  - The three diffuse projection systems arising in the brainstem, that is,
      noradrenergic projection originating in the locus coeruleus, serotonergic
      projection from the dorsal raphe nucleus, and cholinergic projection from neurons
      gathering in the laterodorsal tegmental nucleus and scattering in the
      pedunculopontine tegmental nucleus, may function as controllers of sleep and
      wakefulness. We have investigated the functional roles of these projections by
      recording neuronal activity in these brainstem nuclei and by stimulating the
      brainstem nuclei. It is suggested that the projection from the locus coeruleus is
      an arousal system; the function of the serotonergic projection is still
      mysterious, since these neurons are active specifically during waking; activation
      of the noradrenergic projection excites the upper brain sites whereas activation
      of the serotonergic projection depressed them. It is clear that a group of
      cholinergic neurons constitute a system to induce and maintain paradoxical sleep.
      The cholinergic projection may also have the role to induce a rapid, transient
      elevation of the vigilance level by its phasic response to novel, unfamiliar
      stimuli.

PMID- 9599731
TI  - Self-esteem in children with nocturnal enuresis and urinary incontinence:
      improvement of self-esteem after treatment.
AB  - A study of self-esteem before and after medical treatment was performed in
      children with primary nocturnal enuresis (NE) and urinary incontinence (UI). The
      NEUI children and the controls were recruited from the normal population in the
      town of Umea, Sweden. In total, 66 NEUI children and 64 controls entered the
      study. Clinical examination, laboratory and psychological tests were performed
      before the start of treatment. Follow-up investigations were done 3 and 6 months
      after the start of treatment. To assess self-esteem we used the Swedish self
      esteem questionnaire 'I think I am'. Compared to controls, the NEUI children had
      significant impairment of self-esteem before the start of treatment. Within the
      NEUI group, boys had lower self-esteem than girls. After 6 months of treatment,
      the NEUI children had the same levels of self-esteem as the control group. The
      NEUI children that had become totally dry had significantly better self-esteem at
      6-month follow-up as compared to the NEUI children with persisting NEUI problems.
      In conclusion, the study shows that NEUI children have low self-esteem and that
      their self-esteem may be normalized with proper treatment.

PMID- 9599732
TI  - Comments on pediatric elimination dysfunctions: the Whorf hypothesis, the
      elimination interview, the guarding reflex and nocturnal enuresis.
AB  - AIMS OF STUDY: This paper addresses pediatric elimination disorders including
      nocturnal enuresis from the perspectives of terminology (the Whorf hypothesis),
      the elimination interview, and the guarding reflex. METHODS: The elimination
      interview and a modern model of normal voiding function, including the guarding
      reflex, are explained. RESULTS: The language of voiding dysfunction influences
      our perception of it. Nocturnal enuresis, and all other voiding dysfunctions,
      should be evaluated by a careful elimination interview. The guarding reflex may
      fit into an evolving etiologic paradigm for nocturnal enuresis. CONCLUSIONS: (1)
      Words and phrases of eliminology should aim for simplicity, clarity and accuracy.
      (2) Urologists need to perfect their eliminology skills vis-a-vis the elimination
      interview. (3) The role of the guarding reflex in nocturnal enuresis and all
      other voiding dysfunctions should be critically examined.

PMID- 9599728
TI  - Animal models of human response to dioxins.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class
      of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor
      (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable
      and as a result, human exposure is chronic and widespread. Studies of highly
      exposed human populations show that dioxins produce developmental effects,
      chloracne, and an increase in all cancers and suggest that they may also alter
      immune and endocrine function. In contrast, the health effects of low-level
      environmental exposure have not been established. Experimental animal models can
      enhance the understanding of the effects of low-level dioxin exposure,
      particularly when there is evidence that humans respond similarly to the animal
      models. Although there are species differences in pharmacokinetics, experimental
      animal models demonstrate AhR-dependent health effects that are similar to those
      found in exposed human populations. Comparisons of biochemical changes show that
      humans and animal models have similar degrees of sensitivity to dioxin-induced
      effects. The information gained from animal models is important for developing
      mechanistic models of dioxin toxicity and critical for assessing the risks to
      human populations under different circumstances of exposure.

PMID- 9599734
TI  - Current trends, diagnosis, and treatment of enuresis.
AB  - This survey describes the evolution of our concept of monosymptomatic bedwetting
      over the last decades. It takes you briefly through psychology and enuresis. The
      minor role of bladder pathology is described ending up with focusing on the
      mismatch between bladder capacity at night-time and urine production.
      Monosymptomatic bedwetting should currently be regarded as an umbrella diagnosis
      allocated to children where daytime urinary problems have been excluded. Within
      the diagnosis of monosymptomatic bedwetting we can nowadays identify at least two
      groups. One is related to children who have a large night-time urine production
      and a normal bladder capacity, and the other is related to children who have a
      large night-time production, but a bladder capacity too small for the normal
      urine production. The genetic aspects are currently investigated. The results and
      this kind of research will probably end up in a further subgrouping.

PMID- 9599733
TI  - Daytime functional bladder capacity as a predictor of response to desmopressin in
      monosymptomatic nocturnal enuresis.
AB  - OBJECTIVE: The objective of this study was to identify a cost-effective method of
      predicting a therapeutic response to desmopressin (DDAVP) by correlating daytime
      functional bladder capacity, age and urine osmolalities in patients with
      monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: Thirty-five children
      out of 51 who initially presented to our institutions were included in the study.
      The remainder was excluded for lack of complete data. Constipation was actively
      addressed and was managed by administration of evening enemas for 3 consecutive
      days and dietary adjustment prior to initiating the study. Each micturition as
      measured throughout the day and the maximal daytime functional bladder capacity
      was determined as the largest void over a 2-day period. Urine samples were
      collected at home at 08:00, 16:00 and 22:00 (times that would best reflect the
      fluctuations in plasma vasopressin levels). Intranasal DDAVP was then
      administered, titrating the dose over a 2-week period. The initial dose was 10
      micrograms and the dose was increased 10 micrograms every 3 days. RESULTS: The
      response to DDAVP was then evaluated and of the 35 children, 27 demonstrated a
      complete response to DDAVP (all at doses between 10 and 30 micrograms). These
      were then related to the possible predictive factors. There was a significant
      correlation between a high maximum daytime functional bladder capacity and
      response to DDAVP (p = 0.006). Similarly, age was also predictive of a good
      response to DDAVP treatment (p = 0.008). However, spot urine osmolalities were
      not predictive of a response to DDAVP (p > 0.1). CONCLUSIONS: Functional bladder
      capacity is a reliable predictor of response to desmopressin; children with
      larger capacities are more likely to exhibit a successful response. Older
      children have a better response rate than younger ones. Spot urine osmolality
      measured on specimens collected in the home setting is not predictive of response
      to desmopressin.

PMID- 9599735
TI  - Total genome scan analysis in a single extended family for primary nocturnal
      enuresis: evidence for a new locus (ENUR3) for primary nocturnal enuresis on
      chromosome 22q11.
AB  - OBJECTIVE: In this study we focussed on a single large family to maximize the
      possibility of recognizing a single locus. This family alone could raise a lod
      score above 3, i.e. sufficient by tradition for assignment of a locus. METHODS:
      The family consists of 11 children and 26 grandchildren in whom monosymptomatic
      primary nocturnal enuresis (PNE) is segregating in three generations. A genome
      scanning with about 800 polymorphic marker systems was used to localize a
      chromosome area for the trait and to narrow down the candidate region. RESULTS:
      Total genome scan and multipoint analysis map PNE to chromosome 22 between the
      markers D22S446 and D22S343 with a multipoint lod score of 4.51. CONCLUSION: In
      the candidate area for PNE, the gene GNAZ is mapped. GNAZ has a transducin
      function in eye and brain and is an obvious candidate gene for PNE.

PMID- 9599736
TI  - Lower urinary tract problems in patients with enuresis.
AB  - OBJECTIVE(S): Two hundred and thirty-eight children (170 males, and 68 females)
      with nocturnal enuresis were retrospectively studied for lower urinary tract
      problems. Surgical correction of subclinical organic obstruction in the lower
      urinary tract was evaluated for the improvement of bed-wetting. METHODS: One
      hundred and fifty-five micturating cystourethrography (MCU), and 89 urodynamic
      studies were performed. Optic internal urethrotomy was done in a boy, and
      meatoplasty in a girl for urethral 'ring' stenosis (URS). RESULTS: Nocturnal
      enuresis was found in 153 cases and nocturnal enuresis associated with daytime
      enuresis in 67 cases. Vesicoureteral reflux was found in 30, URS in 42, and
      posterior urethral valve in 3 cases on MCU. Detrusor instability was recognized
      in 39.4% of 38 cases of nocturnal enuresis associated with daytime enuresis and
      in 25.0% of 51 cases of nocturnal enuresis. Surgery brought 73.8% improvement of
      bed-wetting in 42 cases. CONCLUSIONS: Surgical correction of subclinical
      obstruction in the lower urinary tract might contribute to the earlier resolution
      of bed-wetting in children with nocturnal and/or diurnal enuresis.

PMID- 9599737
TI  - The arginine-vasopressin secretion profile of children with primary nocturnal
      enuresis.
AB  - OBJECTIVE: The aim of this group of studies was to determine the relationship
      between primary nocturnal enuresis and arginine-vasopressin (AVP) secretion.
      METHODS: The first study compared the 24-hour AVP secretion profiles of an
      enuretic group and a control group. Blood samples were collected every hour. In
      the second study, we compared nocturnal AVP secretion in group A, with low
      urinary osmotic pressure (UOP) and large nocturnal urinary volume (NUV), with
      that of group D, with normal UOP and small NUV. The plasma AVP level was measured
      at 30-min sampling intervals. In the third study, the change in nocturnal AVP
      secretion from before to after treatment was determined. RESULTS: The plasma AVP
      level was significantly lower in the enuretic group from 23:00 through 04:00 h.
      The mean plasma AVP level was significantly lower in group A than in group D at
      all points of measurement. The mean nocturnal AVP level in group A (0.64 +/- 0.23
      pg/ml) was lower than that in group D (1.43 +/- 0.72 pg/ml) (p < 0.0001). The
      mean nocturnal AVP level after treatment was significantly increased, from 0.47
      pg/ml before treatment to 0.78 pg/ml after treatment (p = 0.01). However, a
      significant increase was noted in only 10 cases. CONCLUSIONS: These findings
      suggest that decreased nocturnal AVP secretion is one of the causes of bed
      wetting. However, the improvement of bed-wetting was not solely due to the
      increased nocturnal AVP secretion.

PMID- 9599738
TI  - Classification based on overnight simultaneous monitoring by
      electroencephalography and cystometry.
AB  - OBJECTIVES: To evaluate the features of the clinical findings in three types
      (types I, IIa, IIb) of enuresis, classified by overnight simultaneous monitoring
      by electroencephalography (EEG) and cystometry (CM). METHODS: We performed a test
      to evaluate bladder capacity, arousal response and the pattern of nighttime
      urination in sucklings and infants. RESULTS: As for the values of enuretic
      bladder capacity (EBC), the smallest were found in enuresis type IIb. As for
      arousal response, enuresis type I showed the best, while enuresis type IIa showed
      the worst response. With regard to the pattern of nighttime urination in
      sucklings and infants, all sucklings had a stable bladder in the sleep state and
      urinated in the pattern of type IIa. The arousal response to bladder distention
      indicating type I appeared at the age of about 2 or 3. CONCLUSIONS: The smallest
      EBC in patients with enuresis type IIb represented a bladder dysfunction in the
      sleep period. It was observed that patients with enuresis type I had the best
      arousal function while those with enuresis type IIa had the worst arousal
      function. All sucklings urinated unconsciously during sleep in the pattern of
      type IIa. The arousal response to bladder distention indicating type I, which was
      not observed below the age of 1 year, was thought to appear at the age of about 2
      or 3 years. If this change has not appeared by the age of 3, bed-wetting might
      persist after the age of 5.

PMID- 9599739
TI  - Therapy concept in enuretic children.
AB  - More than 700 children aged between 5 and 15 years were treated at the University
      of Vienna Department of Urology during the last 10 years. The therapeutic
      approach was based on a complex diagnostic scheme to define the individual
      problem of each enuretic child. Generally speaking the enuresis problem turned
      out to be a symptom of delayed maturation of fine motor control [1] or sleep and
      hormone secretion rhythm during day and night hours. In a high percentage of
      enuretic children, no major physical problem or disease could be found, but the
      possibility of a physical problem, especially a neurourological problem, should
      not be ignored. Nonneurogenic discoordinated voiding in children can be treated
      by cognitive flow-triggered feedback training [2, 3] while overproduction of
      urine during sleep is reduced by antidiuretic hormone therapy with desmopressin
      (DDAVP; 1-deamino-8-D-arginine-vasopressin), a synthetic analogue of antidiuretic
      hormone.

PMID- 9599740
TI  - Nocturnal enuresis: basic facts and new horizons.
AB  - Nocturnal enuresis in children is quite seldom due to psychological factors.
      Instead, it is caused by a hereditary delay in maturation of the somatic
      mechanisms (reduction of nocturnal urine production, relaxation of the bladder
      during sleeping hours, and a normal arousal to a full bladder) which prevent the
      child from wetting the bed. Doctors treating bedwetting children have often used
      an expectant attitude because nocturnal enuresis has been looked upon as self
      limiting and innocent. According to recent research, this is not true. In
      children aged 7 years, more than 5% and in the adult population 0.5% report
      nocturnal enuresis. Thus, many enuretic children will remain bedwetters for life
      if left untreated. Furthermore, the child is ashamed and feels guilt because of
      his nocturnal enuresis which threatens to give a significant impairment of self
      esteem at an age when an intact self-image is extremely important for an optimal
      development of the child's personality. Treatment should be given when the
      enuretic child wants to sleep dry.

PMID- 9599741
TI  - Effects of systematic treatment based on overnight simultaneous monitoring of
      electroencephalography and cystometry.
AB  - OBJECTIVE: To clarify the effects of systematic treatment based on overnight
      simultaneous monitoring by electroencephalography (EEG) and cystometry (CM) on
      each type of enuresis. METHODS: For enuresis type I, the change in the awakening
      response during the conditioning treatment with a therapeutic machine was
      observed. For enuresis type IIa, the effect of imipramine on the EEG was
      observed. For enuresis type IIb, the effect of oxybutynin hydrochloride on the
      cystometrogram (CMG) was observed. RESULTS: Values, in which the awakening score
      on the second night was subtracted from the score on the last night, were
      significantly higher in the effective cases than in the unchanged cases. Out of
      the 3 patients in whom imipramine was effective, an awakening response on the EEG
      was observed in 2. Neither of the 2 unchanged cases showed an awakening response.
      Out of 4 patients in whom oxybutynin hydrochloride was effective, uninhibited
      contractions (UIC) on the CMG disappeared in 3. UIC stopped in neither of the 2
      unchanged cases. CONCLUSIONS: Improvement of the awakening response plays an
      important role in the effectiveness of conditioning treatment with our
      therapeutic machine. The generation of awakening response is thought to be the
      most important result of imipramine directly concerned with its clinical effect
      on enuresis type IIa. The main result with oxybutynin hydrochloride in enuresis
      type IIb is thought to be related to its antispasmodic effect.

PMID- 9599742
TI  - [Angiolog].

PMID- 9599743
TI  - [Endocrinology].

PMID- 9599744
TI  - [Current developments in hematology and internal medicine oncology].

PMID- 9599745
TI  - [Cardiology. Assessment of current status and prospects].

PMID- 9599746
TI  - [Nephrology. Developments in clinical nephrology since 1945].

PMID- 9599747
TI  - [Pneumology].

PMID- 9599748
TI  - [Rheumatology].

PMID- 9599749
TI  - [Success and prospects in gastroenterology].

PMID- 9599750
TI  - [Type 2 diabetes].

PMID- 9599751
TI  - [26-year-old patient with epigastric pain and cholestasis. Primary sclerosing
      cholangitis].

PMID- 9599752
TI  - [18-year-old patient with hypercalcemia, hypophosphatemia, nephrocalcinosis and
      normal iPTH values. Primary hyperparathyroidism].
AB  - We report an 18-year old woman with surgically proven primary hyperparathyroidism
      (pHPT) and normal intact parathyroid hormone (iPTH) serum levels. The reason for
      this rare biochemical presentation are possible biologically active amino
      terminal parathyroid hormone polypeptide fragments not detected by the widely
      used two-site immunoradiometric parathyroid hormone assay (PTH IRMA). Diagnosis
      and therapy of primary hyperparathyroidism therefore should not exclusively rest
      on the finding of hypercalcemia coupled with an elevated iPTH level.

PMID- 9599753
TI  - [Therapy of hepatitis C-associated extrahepatic diseases].

PMID- 9599754
TI  - [Secondary prevention of recurrent transient ischemic attacks].

PMID- 9599755
TI  - [Thalassemia minor. Drug intolerance and psychiatric manifestations].

PMID- 9599756
TI  - [Low-molecular-weight heparins].

PMID- 9599757
TI  - [Therapeutic concept of hereditary thrombophilia].

PMID- 9599758
TI  - [Combination drug therapy with anti-arrhythmia agents. Effective--superfluous-
      dangerous?].

PMID- 9599759
TI  - [Perinatal hemolytic disease. Part 1: physiopathology].
AB  - Perinatal hemolytic disease is characterized by the destruction of fetal red
      blood cells by maternal antibodies directed against membrane antigens and can
      lead to immune fetal hydrops. More than 250 blood group antigens have been
      described. After considering the particular situation of ABO incompatibility,
      this article describes the classification of red blood cells antigens, with
      particular reference to the Rhesus system. Other antigens such as Kell, Kidd,
      Duffy, MNSs, P and Lutheran are also considered.

PMID- 9599760
TI  - [Choroid plexus cysts and risks of chromosome anomalies. Review of the literature
      and proposed management].
AB  - OBJECTIVE: We propose to specify the different criteria of estimation and
      management in presence of a ultrasound discovery of a choroid plexus cyst.
      METHOD: A detailed review of the literature about this subject allowed to better
      apprehend the different attitudes taken up by the authors. RESULTS: Fetal choroid
      plexus cysts (CPC) are potentially useful markers for trisomy 18 in as much as
      they are present in about 50% of affected fetuses and they are easily seen in the
      standard biparietal diameter view which is obtained for all routine ultrasound
      scans. However, advice is contradictory as to whether karyotyping should be
      proposed for all fetuses (1-2% of the population) where fetal CPC are diagnosed.
      CONCLUSION: The review of the literature show that the majority of the authors
      advocate amniocentesis when the CPC is associated with another ultrasound
      abnormality. Isolated, it imposes regular and meticulous morphologic ultrasound
      supervision to search for another possible associated ultrasound abnormality, if
      necessary, in a prenatal diagnosis center.

PMID- 9599761
TI  - [Maternal and congenital syphilis].
AB  - Testing for syphilis during pregnancy reveals a positive serologic status in
      0.02% of cases. However, a 66% rate of stillbirths is noted in women who are
      infected and who have not benefited from any treatment. Routine screening is at
      present performed during the early stages of pregnancy but a second serologic
      test during the third trimester is useful in the diagnosis of a late infection
      especially in drug users or HIV (human immunodeficiency virus) positive patients.
      Congenital syphilis is diagnosed in utero when a positive maternal serologic
      status is associated with ultrasound images showing fetal abnormalities; these
      include hepatosplenomegaly, hyperechogenic bowel, signs of bowel obstruction or
      fetal hydrops. Maternal syphilis is treated by delayed action penicillin and is
      indicated even for patients allergic to the antibiotic which in this particular
      case is delivered after desensitization. First line therapy by intravenous
      penicillin is indicated when confronted with the following high risk factors of
      congenital syphilis: an elevated titre of VDRL (venereal disease research
      laboratory) at the time of diagnosis or delivery, unknown date of the precise
      onset of the infection, the appearance of a rash or of a chancre during
      pregnancy, ultrasound fetal abnormalities or late therapy during the third
      trimester. Treatment of the new-born child will depend on the results of
      clinical, serologic and X-ray evaluation. Long term follow-up for at least a year
      is mandatory.

PMID- 9599762
TI  - [Cytomegalovirus infection in pregnant women. Seroepidemiological prospective
      study in 1,018 women in Isere].
AB  - Cytomegalovirus (CMV) is the leading cause of viral congenital infections. In
      children, the consequences may be severe, especially in case of maternal primary
      infection during pregnancy. A prospective study was carried out in the department
      of Isere, in 1,018 pregnant women, in order to establish the seroprevalence of
      CMV, the frequency of primary infections during pregnancy and the associated risk
      factors. The overall seroprevalence was 51.5%; it increased significantly with
      age, parity, and low socioeconomic status. It was higher in women born in the
      South of France (51.6%) than in those born in the North (37.4%). Among a total of
      878 women with serological follow-up, 7 primary infection cases (0.8%) were
      observed. Seventeen women (1.9%) presented border IgM values in the first serum,
      and these values were not related to recent infection. Extrapolation of the
      results to the whole department of Isere, suggests that each year about 100
      pregnant women would be concerned by CMV primary infection, with 2 or 3 cases of
      death or severe sequelae in children. In light of these results, the interest of
      serological screening is discussed.

PMID- 9599763
TI  - [Use of ultrasonography as a first-line investigation of the uterus. Results of a
      prospective study].
AB  - OBJECTIVE: To assess the effectiveness of hysterosonography as a first line
      investigation for uterine bleeding in perimenopausal women. METHODS: 185 women
      were enrolled in a prospective study. They underwent a hysterosonography
      indicated for abnormal uterine bleeding or follow-up of a treatment with
      tamoxifene. Patients with a normal cavity or atrophia were scheduled for a
      diagnostic hysteroscopy or a hormonal therapy. Patients with uterine cavity
      abnormalities were scheduled for surgery (operative hysteroscopy or
      hysterectomy). All the patients were clinically followed after the
      hysterosonography or the surgery. Results of hysterosonography were compared to
      data issued from the clinical follow-up or to pathological results when
      available. RESULTS: Hysterosonography was achieved in 179 patients. In all but 1
      case, hysterosonography was well tolerated by the patients. We had no
      complication during or after the examination. Hysterosonography had a high
      sensitivity and specificity in the discrimination of women with normal cavity or
      atrophia from the ones with intrauterine lesions (respectively 96.4% and 98.3%).
      Hysterosonography was also accurate in the distinction of polyps from sub-mucosal
      myomas (sensitivity 88.2 a 90.3%, specificity: 98.6 a 95%). The measurement and
      localization of the lesions were accurate in an equal manner with both
      procedures. Hysterosonography had similar results in women treated with
      tamoxifene, but the failure frequency was significantly higher (13% vs 1.8%) (p <
      0.05). CONCLUSIONS: Hysterosonography appears as a reliable tool for the
      investigation of abnormal uterine bleeding in perimenopausal women. It can
      distinguish women who just need a medical therapy from the ones who will require
      a surgical exploration. It is easy to learn, and well tolerated by the women.
      Hysterosonography is more sensitive and specific than transvaginal sonography in
      the follow-up of patients treated with Tamoxifene.

PMID- 9599764
TI  - [Prospective study of the efficacity of a recent symptomatic-thermal method of
      natural family planning].
AB  - A Belgian pilot-study conducted in the framework of the prospective European
      multi-center study (University of Dusseldorf) tried to establish the use
      effectiveness (a sine qua non condition for its acceptance in Europe) of natural
      family planning. MATERIAL AND METHODS: 84 participants provided data (sympto
      thermal chart and related information) on 1,750 cycles where family planning
      intention was to avoid a pregnancy. The average age of the women was 32 years. A
      contraceptive method (mainly oral contraceptives) was employed previously by 61%
      of them. The sympto-thermal method used by the test group highlights the
      beginning and the end of the menstrual cycle's fertile period by a double check.
      As to the start of the fertile period, the criteria are: a calculation on the
      length of the previous twelve cycles and the first sign of mucus at either the
      vulva or the cervix. Indicators of the end of this phase are: the third day of
      high temperature and the fourth evening after either the peak mucus day or the
      peak cervix day. 75% of the women involved generally use the cervical auto
      palpation. RESULTS: No method failure at all has been detected. Two unplanned
      pregnancies occurred due to user failure. The total Pearl index for the study was
      1.4. When examining only those cycles (85% of the reported cycles) where no
      protected sexual intercourse occurred during the fertile phase, practical
      efficacy of the method analysed was 1.8 according to Pearl index. Furthermore,
      taking into account protected and unprotected sexual intercourse occurred during
      the fertile phase, we observed that sexual abstinence was practised during the
      "risk" period of 75% of the cycles. CONCLUSIONS: The results of this test study
      demonstrate the practical efficiency of a modern natural family planning method.
      The high level of cycles during which periodic abstinence was employed testify to
      the acceptability of the method used.

PMID- 9599765
TI  - [Mouchel transmuscular incision: a closure variant].
AB  - Low transverse incision according to Mouchel is an interesting technique in
      Gynecology-Obstetrics. Two closure methods are generally used but both inevitably
      leave a dead-space in the subaponevrotic zone. A simple technical variation,
      which is rapid and easily reproducible, allows to overcome this inconvenience.

PMID- 9599766
TI  - [Security by using a micro-optic introduced by the Veress needle in
      laparoscopies].
AB  - Blind introduction of the Veress needle or the umbilical trocar is the cause of 1
      to 4 injuries per 1,000 laparoscopies, particularly in case of abdominal
      adhesions. The aim of this experimental randomized study was to determine whether
      the needlescope can improve safety compared with the routinely used syringe test.
      Adult female rabbits were randomized into two groups of 20. Abdominal adhesions
      were created surgically in all animals. Three weeks later, a pneumoperitoneum was
      provoked under general anesthesia and five trocars were introduced into each
      animal after the needlescope test or the syringe test. The needlescope yielded
      high sensitivity. Adhesion formations were localized in 95% of the cases.
      Inversely, the syringe test localized adherences in only 50% of the cases. The
      number of organ injuries was identical for the two tests: 6.06 versus 6.25%.

PMID- 9599767
TI  - [Fetal goiter with hypothyroidism. A case report].

PMID- 9599768
TI  - [Postpartum cerebral thrombophlebitis. A case secondary to acquired antithrombin
      III deficiency].
AB  - The cerebral thrombophlebitis is a rare complication of the pregnancy and the
      postpartum. We report a case of a 21 year-woman presenting a post-partum cerebral
      thrombophlebitis, secondary to an acquired deficiency of antithrombin III. The
      clinical symptoms of cerebral thrombophlebitis can be misleading. The angiography
      and the magnetic resonance imaging permit the diagnosis. The treatment is relied
      on anticoagulating heparin therapy. This treatment will be adapted in case of
      coagulation's factors deficiency that must be searched in any thromboembolic
      accident having an unusual localization.

PMID- 9599769
TI  - [Liposarcoma of the breast. A case report].
AB  - Liposarcoma of the breast is an unfrequent tumor that can be found in 45-55-year
      old women, usually with benign clinical and radiological characteristics. We
      report the case of a 50-year-old patient treated with menopausal hormonal
      replacement therapy, for whom mammographic screening revealed a solid tumor.
      Lumpectomy was performed and histology reported liposarcoma of the breast. Two
      years after surgery alone no relapse was observed. Our case report underlines the
      possibility of discovering this type of tumor by means of mammographic
      examination performed during menopausal hormonal replacement therapy. It suggests
      good prognosis after surgery alone.

PMID- 9599771
TI  - [Using the Endo Stitch forceps via the vagina: purely by palpation?].

PMID- 9599770
TI  - [Evaluation and results of a clinical teaching method in gynecologic semeiology].
AB  - OBJECTIVE: To describe a teaching method for students in gynecological semeiology
      and evaluate the results. METHODS: Theoretical and practical aspects of the
      course were designed to meet a set of objectives. Theoretical teaching included
      one or two objectives per class. Clinical examination was initially taught on an
      anatomical mannikin, then on a patient under general anesthetic. Students were
      evaluated after four 3-hour classes by means of multiple choice questions (MCQ)
      and a clinical case report. The course was evaluated by means of a questionnaire,
      asking the students for their opinion. RESULTS: Twenty-five students out of 31
      were tested in 1995-1996. The MCQ results were good with 84% correct answers (78%
      for first cycle and 89% for second cycle students). It was not possible to assess
      the clinical case report. The students appreciated the scientific and educational
      quality of the course, but felt that the sessions were too short and too
      infrequent. CONCLUSION: This teaching method for students in gynecological
      semeiology was successful in its first year of application. This experiment may
      result in the development of a course combining university teaching and practical
      work leading to a common theory/practical examination.

PMID- 9599772
TI  - [Can a very simple test justify using a new intervention in stress urinary
      incontinence? The Ulmsten prosthetic sub-urethral support].

PMID- 9599773
TI  - Annotation: day and night wetting in children--a paediatric and child psychiatric
      perspective.

PMID- 9599774
TI  - Annotation: night wetting in children: psychological aspects.

PMID- 9599775
TI  - Developmental catch-up, and deficit, following adoption after severe global early
      privation. English and Romanian Adoptees (ERA) Study Team.
AB  - The extent of developmental deficit and catch-up following adoption after severe
      global early privation was examined at 4 years in a sample of 111 Romanian
      children who came to the U.K. before the age of 2 years, and compared with
      respect to their functioning at the same age to a sample of 52 U.K. adopted
      children placed before the age of 6 months. The measures at 4 years included
      height, head circumference, and general cognitive level (assessed on both the
      McCarthy and Denver Scales). The children from Romania were severely
      developmentally impaired at the time of U.K. entry, with about half below the
      third percentile on height, on weight, on head circumference, and on
      developmental quotient. Many were also in a poor physical state with recurrent
      intestinal and respiratory infections. The catch-up in both physical growth and
      cognitive level appeared nearly complete at 4 years for those children who came
      to the U.K. before the age of 6 months, despite the fact that their background
      prior to U.K. entry was similar to the children who came to the U.K. when older.
      The developmental catch-up was also impressive, but not complete, in those placed
      after 6 months of age. The mean McCarthy General Cognitive Index was 92 compared
      with 109 for the within-U.K. adoptees. The strongest predictor of level of
      cognitive functioning at 4 years was the children's age at entry to the U.K. It
      was concluded that the remaining cognitive deficit was likely to be a consequence
      of gross early privation, with psychological privation probably more important
      than nutritional privation. A further follow-up at age 6 years will determine
      whether there is continuing recovery after 4 years.

PMID- 9599776
TI  - The relationship between mutual family relations and child psychopathology.
AB  - The associations of the mutual mother-child, father-child, and mother-father
      relationship and various patterns of family relations with child psychopathology
      were investigated in a sample of 137 families referred to outpatient mental
      health services. Assessment of the relative association of the different family
      dyads showed that both the mother-child and the mother-father relationship were
      related to child problem behaviour. However, whereas the mother-child
      relationship was consistently more related to externalising behaviour, the mother
      father relationship was particularly related to internalising behaviour. Our
      findings gave clear support for the cumulative risk model: having more negatively
      qualified relationships was associated with more problem behaviour. Furthermore,
      our results suggested a protective influence of the parent-child relationship:
      having one or two positive parent-child relationships was associated with less
      problem behaviour. No support was found for the cross-generational coalition
      hypothesis. Implications for future research are discussed.

PMID- 9599777
TI  - The impact of family transition on the development of delinquency in adolescent
      boys: a 9-year longitudinal study.
AB  - The purpose of this study was to examine prospectively the impact of family
      transition on deviant development in a sample of 427 French-Canadian boys
      participating in a longitudinal study from kindergarten onwards. During the
      course of the study some boys experienced family transition. We grouped the boys
      by developmental period and number of marital transitions they experienced:
      divorced between ages 6 and 11; divorced between ages 12 to 15; remarried between
      ages 6 and 11; and remarried between ages 12 and 15. From ages 11 to 15 we
      assessed boys' delinquency and their family processes (parental supervision,
      punishment, and communication) annually. The results suggest that boys who
      experienced remarriage between ages 12 and 15 are at greater risk for
      delinquency. In particular, they showed evidence of comparatively more theft and
      fighting at earlier ages than their peers from families that had remained intact.
      At similar points in development, they perceived less expressive parent-child
      relationships. Finally, these boys also perceived less monitoring by their
      parents, both overall and at different points in adolescence.

PMID- 9599778
TI  - Awareness of language in children who have reading difficulties: historical
      comparisons in a longitudinal study.
AB  - We look at the awareness of grammatical distinctions in children with reading
      difficulties, and at their ability to use this awareness in order to learn about
      the conventional spellings for morphemes like "ed" at the end of past verbs.
      Using longitudinal methods we show that, initially, children who are to become
      poor readers are actually better in this aspect of spelling and also in
      grammatical awareness tasks than younger children of the same reading level: but
      they are worse than these other children in tasks that tax their knowledge of
      phonologically based letter-sound correspondences. Later on, however, the poor
      readers lose their initial advantages in the conventional spelling of morphemes.
      We conclude that poor readers are initially held back by a failure to learn about
      letter-sound correspondences, and that this deprives them of successful reading
      experience, which in turn hampers the growth of their grammatical awareness and
      their learning how to spell morphemes.

PMID- 9599779
TI  - Verbal and nonverbal abilities in the Williams syndrome phenotype: evidence for
      diverging developmental trajectories.
AB  - One commonly cited feature of Williams syndrome is a characteristic dissociation
      between relatively spared language skills and severely impaired nonverbal
      abilities. However, the actual evidence for a dissociation between verbal and
      nonverbal abilities in Williams syndrome is equivocal. In two separate studies we
      examined these abilities in 16 individuals showing the Williams syndrome
      phenotype. When considered as a whole, the group did have significantly superior
      verbal abilities, but this difference was caused by a large discrepancy in
      abilities in only a small number of individuals. In both studies there was a
      clear, linear relation between individuals' verbal ability, and the magnitude of
      their verbal-nonverbal discrepancy. We suggest that these results are best
      explained in terms of verbal ability developing at a faster rate than nonverbal
      ability in this disorder. We discuss how this model of differential rates of
      development has the potential to reconcile the apparently inconsistent findings
      in this area.

PMID- 9599780
TI  - Executive and motivational control of performance task behavior, and autonomic
      heart-rate regulation in children: physiologic validation of two-factor solution
      inhibitory control.
AB  - Forty-two (42) children (mean age 10.6 years) from mainstream public (N = 22) and
      therapeutic schools (N = 20) completed performance tasks assessing executive and
      motivational influences on motor responses. In a separate protocol, children
      underwent physiologic challenges of paced breathing and supine to standing
      postural change, while heart rate was continuously monitored. Executive control
      was associated with vagal modulation of respiratory driven, high-frequency heart
      rate variability (t = 2.20, p < .03), whereas motivational control was associated
      with sympathetic modulation of posturally driven, low-frequency heart-rate
      variability (t = -2.22, p < .03). These findings supported a two-factor solution
      of inhibitory control derived in a previous study.

PMID- 9599781
TI  - Peer problems of children with hemiplegia in mainstream primary schools.
AB  - A representative sample of 55 mainstreamed 9-10-year-olds with hemiplegia were
      compared with all classmates on sociometric measures of popularity and
      friendship, and with 55 matched controls on measures of victimization. Children
      with hemiplegia were more rejected and less popular, had fewer friends, and were
      more often victimized; they were not more likely to be bullies themselves. These
      differences were not fully accounted for by group differences in teacher
      estimated IQ and behaviour. Possible explanations range from neurologically
      determined deficits in mentalizing skills to peer prejudices about children with
      disabilities. The development of appropriate intervention strategies should be a
      high priority, particularly since peer problems not only result in current
      distress but also predict psychosocial problems in the future.

PMID- 9599782
TI  - Adolescent abortion and parental notification: evidence for the importance of
      family functioning on the perceived quality of parental involvement in U.S.
      families.
AB  - This study was an investigation of the relationship between family variables and
      the perceived quality of parental involvement following parental notification of
      an adolescent's decision to have an abortion. Demographics, family religiosity,
      and family functioning variables were examined. Pregnant adolescent clients from
      seven abortion clinics in three states completed a survey assessing their
      perception of the quality of parental involvement and the family variables. Only
      family functioning variables were significantly related to the perceived quality
      of parental involvement. Family adaptability (the family's ability to change its
      power structure, role relationships, and relationship rules in response to
      situational and developmental stress) was the most predictive. Adolescents from
      adaptable families had a more positive experience with parental involvement than
      adolescents from less adaptable families.

PMID- 9599783
TI  - Teacher ratings of externalizing behavior at school entry for boys and girls:
      similar early predictors and different correlates.
AB  - In a test of Patterson's Coercion Theory with young children, 156 children (82
      boys and 74 girls) were studied to assess the extent to which parenting and child
      variables, assessed at 18 months, would predict teacher ratings of externalizing
      child behaviors at age 5. Child playgroup behavior, parent coercion during home
      observations, and marital status each emerged as predictors, whereas child
      temperament, attachment classification, and gender did not. At age 5, the
      correlates of externalizing behaviors differed for boys and girls. Boys rated
      higher on externalizing behaviors by the teachers presented many problems in the
      home and school, whereas externalizing girls did not. In fact, girls rated higher
      on externalizing behaviors performed better on an intelligence test, yet the
      girls perceived themselves as less competent.

PMID- 9599784
TI  - Ethnic variations in children's problem behaviors: a cross-sectional,
      developmental study of Hawaii school children.
AB  - Variations in children's problem behaviors associated with ethnicity and other
      demographic variables were examined in 6-18-year-old children (N = 804) residing
      in a multicultural environment. The Child Behavior Checklist-Teacher's Report
      Form was used to compare the frequency of behavior problems among clinic-referred
      and nonreferred children of Hawaiian, Asian, and Caucasian ethnicities. Children
      who were male, clinic-referred, or of Caucasian or Hawaiian ancestry experienced
      greater levels of behavioral problems. Explanations concerning ethnic variations
      in children's problem behaviors include: teacher's perceptual bias, differences
      in teacher threshold to report problem behaviors, and/or true variations in
      children's behavior.

PMID- 9599785
TI  - Children with symptoms of depression--what do the adults see?
AB  - In order to find out whether parents and teachers report depressive symptoms in
      children with self-reported depression and which features are connected with
      sought psychiatric care, a sample of 5682 prepubertal children was assessed with
      the Children's Depression Inventory (CDI), the Rutter A2 scale (RA) and Rutter B2
      scale (RB). In stepwise regression analysis of parent report, depressed mood,
      unpopularity, social withdrawal, disobedience, inattentiveness, and stealing were
      associated with high CDI scores. The items of the teacher report associated with
      high CDI scores included poor school performance, restlessness, somatic
      complaints, unresponsiveness, being bullied, and absenteeism from school.
      Although the parents and teachers readily saw and reported depressive symptoms in
      children, only for a small minority of children with multiple depressive symptoms
      had psychiatric care been sought or even considered. The symptoms associated with
      sought psychiatric care for depressed children were somatic (soiling, asthma) and
      behavioural (disobedient, restless). The results indicate that a large number of
      children with multiple depressive symptoms are left without necessary psychiatric
      assessment and help.

PMID- 9599786
TI  - Children's judgements about pain at age 8-10 years: do extremely low birthweight
      (< or = 1000 g) children differ from full birthweight peers?
AB  - Children's judgements about pain at age 8-10 years were examined comparing two
      groups of children who had experienced different exposure to nociceptive
      procedures in the neonatal period: extremely low birthweight (ELBW) < or = 1000 g
      (N = 47) and full birthweight (FBW) > or = 2500 g (N = 37). The 24 pictures that
      comprise the Pediatric Pain Inventory, depicting events in four settings:
      medical, recreational, daily living, and psychosocial, were used as the pain
      stimuli. The subjects rated pain intensity using the Color Analog Scale and pain
      affect using the Facial Affective Scale. Child IQ and maternal education were
      statistically adjusted in group comparisons. Pain intensity and pain affect
      related to activities of daily living and recreation were significantly higher
      than psychosocial and medically related pain on both scales in both groups of
      children. Although the two groups of children did not differ overall in their
      perceptions of pain intensity or affect, the ELBW children rated medical pain
      intensity significantly higher than psychosocial pain, unlike the FBW group.
      Also, duration of neonatal intensive care unit stay for the ELBW children was
      related to increased pain affect ratings in recreational and daily living
      settings. Despite altered response to pain in the early years reported by
      parents, on the whole at 8-10 years of age ELBW children judged pain in pictures
      similarly to their term peers. However, differences were evident, which suggests
      that studies are needed of biobehavioural reactivity to pain beyond infancy, as
      well as research into beliefs, attitudes, and perceptions about pain during the
      course of childhood in formerly ELBW children.

PMID- 9599787
TI  - Debate and argument: the sex ratios of the sibs of children with psychiatric
      diagnoses.

PMID- 9599788
TI  - The gene for familial Mediterranean fever has been identified.

PMID- 9599789
TI  - Bone dysplasias due to abnormalities in type II collagen.

PMID- 9599790
TI  - Risk factors for gout: a hospital-based study in urban black South Africans.
AB  - The clinical features of 90 Black South African patients with gout seen at a
      large urban hospital were reviewed. The mean age of the patients was 54.3 and
      55.3 years for men and women, respectively. The male:female ratio was 3.3:1. All
      except one of the women were postmenopausal. Seventy-nine percent of patients
      were from the lower income groups of "blue collar" workers, old-age pensioners or
      the unemployed. Polyarticular gout was observed in 44.4% of the patients. Tophi
      were noted in 51.1% of patients but none had a history of renal calculi. Risk
      factors were assessed by comparing the gouty patients to an equal number of age-
      and sex-matched hospital controls. Case-control analysis showed a "white collar"
      occupation (odds ratio = 7.4), obesity (odds ratio = 5.3), alcohol intake (odds
      ratio = 3.5) and hypertension (odds ratio = 3.3) to be significant risk factors
      for gout in the overall group of both men and women. In the subgroup of men only,
      obesity (odds ratio = 7.8), a "white collar" occupation (odds ratio = 6.4),
      hypertension (odds ratio = 4.9) and alcohol intake (odds ratio = 3.5) were
      similarly associated with gout. In women, a history of alcohol intake was the
      only significant risk factor associated with gout (odds ratio = 5.0). These
      findings suggest that in a population where gout was previously rare, changing
      dietary habits and lifestyle, together with improving socioeconomic conditions
      are contributing significantly to the increasing prevalence of the disease.

PMID- 9599791
TI  - Nonsurgical synovectomy in the treatment of arthropathy in Von Willebrand's
      Disease.
AB  - Von Willebrand's disease is the most common inherited bleeding disorder, with an
      overall prevalence in the general population of 0.8% to 1.3%. Hemarthrosis occurs
      mainly in the severest forms of the disease (type III), with a frequency of 3.5%
      to 11%, and can cause severe arthropathy similar to that seen in hemophilia. We
      retrospectively reviewed our experience with nonsurgical synovectomy in the
      treatment of recurrent hemarthrosis with arthropathy in patients with von
      Willebrand's disease. Four of our six patients had type III disease and the
      remaining two had type II disease. The age range was 13 to 63 years. The
      frequency of hemarthrosis prior to synovectomy was one to four per month. One (n
      = 2) or both (n = 1) knees were treated in 4 cases, one (n = 1) or both (n = 1)
      ankles in 3 cases and an elbow in one case. We used yttrium 90 in a dose of 5 mCi
      for one knee, rhenium 186 in a dose of 2 mCi for two ankles and the elbow and
      osmic acid for two knees and one ankle. Clinical and radiological results were
      evaluated six months after synovectomy using the World Federation of Hemophilia
      score. Radiologic lesions remained stable and clinical manifestations improved in
      every case (p < 0.05). Five patients achieved a complete remission. Safety was
      satisfactory. The clinical efficacy of synovectomy done, using radiocolloids or
      osmic acid in arthropathy due to von Willebrand's disease, seems similar to that
      in hemophilia.

PMID- 9599792
TI  - Heterotopic ossification after total hip arthroplasty: risk factors and
      prevention.
AB  - A retrospective review of 168 consecutive total hip arthroplasty procedures done
      in 1983 at the Cochin Teaching Hospital, Paris, France, was conducted to
      determine the rate of occurrence of heterotopic paraarticular ossification and to
      look for risk factors for this complication. None of the patients received
      preventive therapy for heterotopic ossification. Mean age was 66.2 years. The
      reason for arthroplasty was hip osteoarthritis in every case. The index operation
      was the first arthroplasty procedure. Heterotopic ossification was noted in 61.3%
      of patients and was high-grade in 8.3%. The rate of occurrence of heterotopic
      ossification was not influenced by age, gender, joint destruction, preoperative
      osteophytosis, duration of the arthroplasty or the occurrence of complications
      during or after the arthroplasty. However, severe ossification was more common in
      men that in women (12.7% men versus 5.7% women had grade III ossification) and in
      patients operated on by relatively inexperienced surgeons (28/8% grade II and III
      ossifications, versus 14.7% in patients operated on by experienced surgeons). The
      rate of occurrence of heterotopic ossification in the patients who had no risk
      factors (60.9%) was not significantly different from that in the overall study
      population. These data suggest that preventive strategies targeted to specific
      patient subgroups would probably be ineffective, and that routine preventive
      therapy of all total hip arthroplasty patients is warranted.

PMID- 9599793
TI  - Prevalence of vertebral deformities according to the diagnostic method.
AB  - Vertebral deformities are a major complication of osteoporosis. Although their
      prevalence is known to increase with age, the absence of reference criteria
      complicates their radiologic diagnosis. We evaluated variations in the prevalence
      of vertebral deformities according to the diagnostic method used in 291 men and
      262 women older than 50 years included in the European Vertebral Osteoporosis
      Study. Lateral radiographs of the thoracic and lumbar spine were obtained in all
      subjects using standardized parameters. Six morphometric and quantitative methods
      were used to detect vertebral deformities. The prevalence of vertebral
      deformities, the number of vertebral deformities per 100 subjects and the
      prevalence of deformities for each vertebra varied according to the method used.
      With most methods, the percentage of subjects with vertebral deformities and the
      number of vertebral deformities were similar among the men and among the women.
      In the women, the prevalence and the number of vertebral deformities increased
      with age; beyond 70 years of age, however, the prevalence remained stable with
      advancing age, although the number of deformities per patient increased. In men,
      the prevalence of vertebral deformities remained stable with advancing age,
      suggesting that osteoporosis was not the only cause of vertebral deformity in
      this group. In conclusion, the prevalence of vertebral deformities varies
      according to the diagnostic method used. In men, none of the six methods
      evaluated in this study adequately differentiates osteoporotic deformities from
      deformities due to other causes.

PMID- 9599794
TI  - Broadband ultrasound attenuation at the calcaneus measured using a new contact
      ultrasound unit.
AB  - We evaluated a new contact ultrasound device, developed and manufactured in
      France, for measuring broadband ultrasound attenuation at the calcaneus. We first
      studied the influence on measurement results of a number of parameters including
      the nature of the coupling agent, heel position, transducer temperature, and foot
      vasodilation. We then determined the reproducibility of the measurements (2.14 +/
      1.07% in the medium-term) and established reference values in women (n = 612)
      and men (n = 106). Broadband ultrasound attenuation decreased between 25 and 85
      years of age by 34% in women and 17% in men. Sensitivity and specificity for
      detection of decreased bone mass at the calcaneus were 85.5% and 81.5%,
      respectively. Sensitivity and specificity of the measurement at the calcaneus as
      compared to the lumbar spine were 90.7% and 89.1%, respectively. This unit
      intended for screening purposes is very easy to use, and the measurements it
      provides are immediately available. It can be expected to help determine the
      optimal strategy for use of ultrasound in the management of osteoporosis.

PMID- 9599796
TI  - Risk factors for low back pain: an update.

PMID- 9599795
TI  - Lymphoproliferative disorders in rheumatoid arthritis patients on low-dose
      methotrexate.
AB  - Methotrexate is the most widely used second-line treatment in rheumatoid
      arthritis because of its excellent efficacy and safety profile. However, since
      1991, about 100 cases of lymphoproliferative disorders have been reported in
      rheumatoid arthritis patients under methotrexate therapy. Four characteristics
      similar to those in lymphomas associated with immunodeficiency were identified
      during a review of the 48 cases for which detailed information is available. (1)
      Most cases were non-Hodgkin's B-cell lymphomas of the large cell or diffuse mixed
      type. (2) Extranodal involvement (55% of cases) was unusually common. (3)
      Evidence of Epstein-Barr infection was found in 46% of tested patients. (4) Of
      the 14 patients treated by methotrexate withdrawal alone, eight achieved a full
      remission, with follow-ups ranging from one to five years. These characteristics
      suggest a role for two factors: (1) the abnormalities in cell-mediated immunity
      seen in rheumatoid arthritis may promote latent Epstein-Barr virus infection,
      which may in turn lead to proliferation of malignant lymphoid cells; (2) the
      immunomodulatory effects of methotrexate may promote the development not only of
      opportunistic infections but also of Epstein-Barr virus-related
      lymphoproliferative disorders. There is no firm evidence to date that
      methotrexate has a direct oncogenic effect and no excess in malignant diseases
      has been reported with this drug. In conclusion, the rate of occurrence of
      lymphoproliferative disorders induced by low-dose methotrexate therapy remains
      controversial, although the characteristics of the malignancies and the
      possibility of a complete remission after methotrexate withdrawal militate
      against a chance association. Epidemiologic and other studies are needed to
      clarify this issue.

PMID- 9599797
TI  - Vascular complication involving the conus medullaris or cauda equina after
      vertebral manipulation for an L4-L5 disk herniation.
AB  - A case of injury to the cauda equina or conus medullaris after lumbar vertebral
      manipulation is reported. In contrast to all other previously reported cases, no
      migrated disk fragment was demonstrated. Similar to experience at the cervical
      spine, lumbar vertebral manipulation may carry a risk of vascular injury. The
      neurological manifestations in our patient were consistent with compression of
      the Desproges-Gotteron artery by a small L4-L5 disk herniation.

PMID- 9599798
TI  - Lymphoma with regression after methotrexate withdrawal in a patient with
      rheumatoid arthritis. Role for the Epstein-Barr virus.
AB  - We report a new case of large T-cell lymphoma in a rheumatoid arthritis patient
      under low-dose methotrexate (cumulative dose: 750 mg). Serologic tests for the
      Epstein-Barr virus were positive, and the viral RNA was demonstrated in the
      lymphoma cells. As in a few other cases reported in the literature, the clinical
      and laboratory test abnormalities resolved promptly after methotrexate withdrawal
      without anticancer therapy. The patient was still in complete remission at last
      follow-up four years later.

PMID- 9599799
TI  - Extension of reflex sympathetic dystrophy syndrome to a diaphyseal tibial bone
      graft? Report of two cases.

PMID- 9599800
TI  - Acute oligoarthritis in a patient with Bornholm disease. A case-report.

PMID- 9599801
TI  - Fagopyritol B1, O-alpha-D-galactopyranosyl-(1-->2)-D-chiro-inositol, a galactosyl
      cyclitol in maturing buckwheat seeds associated with desiccation tolerance.
AB  - O-alpha-D-Galactopyranosyl-(1-->2)-D-chiro-inositol, herein named fagopyritol B1,
      was identified as a major soluble carbohydrate (40% of total) in buckwheat
      (Fagopyrum esculentum Moench, Polygonaceae) embryos. Analysis of hydrolysis
      products of purified compounds and of the crude extract led to the conclusion
      that buckwheat embryos have five alpha-galactosyl D-chiro-inositols: fagopyritol
      A1 and fagopyritol B1 (mono-galactosyl D-chiro-inositol isomers), fagopyritol A2
      and fagopyritol B2 (di-galactosyl D-chiro-inositol isomers), and fagopyritol B3
      (tri-galactosyl D-chiro-inositol). Other soluble carbohydrates analyzed by high
      resolution gas chromatography included sucrose (42% of total), D-chiro-inositol,
      myo-inositol, galactinol, raffinose and stachyose (1% of total), but no reducing
      sugars. All fagopyritols were readily hydrolyzed by alpha-galactosidase (EC
      3.2.1.22) from green coffee bean, demonstrating alpha-galactosyl linkage.
      Retention time of fagopyritol B1 was identical to the retention time of O-alpha-D
      galactopyranosyl-(1-->2)-D-chiro-inositol from soybean (Glycine max (L.) Merrill,
      Leguminosae), suggesting that the alpha-galactosyl linkage is to the 2-position
      of D-chiro-inositol. Accumulation of fagopyritol B1 was associated with
      acquisition of desiccation tolerance during seed development and maturation in
      planta, and loss of fagopyritol B1 correlated with loss of desiccation tolerance
      during germination. Embryos of seeds grown at 18 degrees C, a condition that
      favors enhanced seed vigor and storability, had a sucrose-to-fagopyritol B1 ratio
      of 0.8 compared to a ratio of 2.46 for seeds grown at 25 degrees C. We propose
      that fagopyritol B1 facilitates desiccation tolerance and storability of
      buckwheat seeds.

PMID- 9599802
TI  - Rice phloem thioredoxin h has the capacity to mediate its own cell-to-cell
      transport through plasmodesmata.
AB  - Rice (Oryza sativa L.) phloem sieve tubes contain RPP13-1, a thioredoxin h
      protein that moves around the plant via the translocation stream. Such phloem
      mobile proteins are thought to be synthesized in the companion cells prior to
      being transferred, through plasmodesmata, to the enucleate sieve-tube members. In
      this study, in-situ hybridization experiments confirmed that expression of RPP13
      1 is restricted to companion cells within the mature phloem. To test the
      hypothesis that RPP13-1 enters the sieve tube, via plasmodesmata, recombinant
      RPP13-1 was expressed in Escherichia coli, extracted, purified and fluorescently
      labeled with fluorescein isothiocyanate (FITC) for use in microinjection
      experiments into tobacco (Nicotiana tabacum L.) mesophyll cells. The FITC-RPP13-1
      moved from the injected cell into surrounding cells, whereas the E. coli
      thioredoxin, an evolutionary homolog of RPP13-1, when similarly labeled and
      injected, failed to move in this same experimental system. In addition, co
      injection of RPP13-1 and FITC-dextrans established that RPP13-1 can induce an
      increase in plasmodesmal size exclusion limit to a value greater than 9.4 but
      less than 20 kDa. Nine mutant forms of RPP13-1 were constructed and tested for
      their capacity to move from cell to cell; two such mutants were found to be
      incapable of movement. Crystal-structure prediction studies were performed on
      wild-type and mutant RPP13-1 to identify the location of structural motifs
      required for protein trafficking through plasmodesmata. These studies are
      discussed with respect to plasmodesmal-mediated transport of macromolecules
      within the companion cell-sieve tube complex.

PMID- 9599803
TI  - Distribution and dynamics of the cytoskeleton in graviresponding protonemata and
      rhizoids of characean algae: exclusion of microtubules and a convergence of actin
      filaments in the apex suggest an actin-mediated gravitropism.
AB  - The organization of the microtubule (MT) and actin microfilament (MF)
      cytoskeleton of tip-growing rhizoids and protonemata of characean green algae was
      examined by confocal laser scanning microscopy. This analysis included
      microinjection of fluorescent tubulin and phallotoxins into living cells, as well
      as immunofluorescence labeling of fixed material and fluorescent phallotoxin
      labeling of unfixed material. Although the morphologically very similar
      positively gravitropic (downward growing) rhizoids and negatively gravitropic
      (upward growing) protonemata show opposite gravitropic responses, no differences
      were detected in the extensive three-dimensional distribution of actin MFs and
      MTs in both cell types. Tubulin microinjection revealed that in contrast to
      internodal cells, fluorescent tubulin incorporated very slowly into the MT arrays
      of rhizoids, suggesting that MT dynamics are very different in tip-growing and
      diffusely expanding cells. Microtubules assembled from multiple sites at the
      plasma membrane in the basal zone, and a dense subapical array emerged from a
      diffuse nucleation centre on the basal side of the nuclear envelope.
      Immunofluorescence confirmed these distribution patterns but revealed more
      extensive MT arrays. In the basal zone, short branching clusters of MTs form two
      cortical hemicylinders. Subapical, axially oriented MTs are distributed in equal
      density throughout the peripheral and inner cytoplasm and are closely associated
      with subapical organelles. Microtubules, however, are completely absent from the
      apical zones of rhizoids and protonemata. Actin MFs were found in all zones of
      rhizoids and protonemata including the apex. Two files of axially oriented
      bundles of subcortical actin MFs and ring-like actin structures in the streaming
      endoplasm of rhizoids were detected in the basal zones by microinjection or
      rhodamine-phalloidin labeling. The subapical zone contains a dense array of
      mainly axially oriented actin MFs that co-distribute with the subapical MT array.
      In the apex, actin MFs form thicker bundles that converge into a remarkably
      distinct actin patch in the apical dome, whose position coincides with the
      position of the endoplasmic reticulum aggregate in the centre of the
      Spitzenkorper. Actin MFs radiate from the actin patch towards the apical
      membrane. Together with results from previous inhibitor studies (Braun and
      Sievers, 1994, Eur J Cell Biol 63: 289-298), these results suggest that MTs have
      a stabilizing function in maintaining the polar cytoplasmic and cytoskeletal
      organization. The motile processes, however, are mediated by actin. In
      particular, the actin cytoskeleton appears to be involved in the structural and
      functional organization of the Spitzenkorper and thus is responsible for
      controlling cell shape and growth direction. Despite the similar structural
      arrangements of the actin cytoskeleton, major differences in the function of
      actin MFs have been observed in rhizoids and protonemata. Since actin MFs are
      more directly involved in the gravitropic response of protonemata than of
      rhizoids, the opposite gravitropsim in the two cell types seems to be based
      mainly on different properties and activities of the actin cytoskeleton.

PMID- 9599804
TI  - Extracellular beta-1,3-glucanases are induced during early somatic embryogenesis
      in Cichorium.
AB  - In leaf tissues of the Cichorium hybrid clone '474' (C. intybus L. var. sativum x
      C. endivia L. var. latifolia), the acquisition and expression of embryogenic
      competence was characterised by the appearance of 15 polypeptides (Boyer et al.,
      1993, Plant Sci 93: 41-53). The 38-kDa proteins were found to be abundantly
      present in conditioned embryogenic medium after the first division of the induced
      cells. These proteins seemed to be glycosylated as indicated by general
      carbohydrate detection methods. Internal amino-acid sequences obtained after
      microsequencing tryptic peptides appeared to be 36-57% homologous with plant beta
      1,3-endoglucanases. In addition, these 38-kDa proteins were recognised by
      antibodies raised against the pathogenesis-related tobacco glucanase PR2a and
      their beta-1,3-glucanase activity was demonstrated by direct detection in
      polyacrylamide gels after electrophoresis. These results strongly suggested that
      the 38-kDa somatic-embryogenesis-related (SER) polypeptides are beta-1,3
      glucanases. Moreover, the level of glucanase activity was nearly three times
      higher in the medium of the embryogenic '474' line than in the medium of a non
      embryogenic line. The possible involvement of the extracellular 38-kDa proteins
      in callose degradation during somatic embryogenesis is discussed.

PMID- 9599805
TI  - Immunocytochemical localization of IdiA, a protein expressed under iron or
      manganese limitation in the mesophilic cyanobacterium Synechococcus PCC 6301 and
      the thermophilic cyanobacterium Synechococcus elongatus.
AB  - Iron-deficiency-induced protein A (IdiA) with a calculated molecular mass of 35
      kDa has previously been shown to be essential under manganese- and iron-limiting
      conditions in the cyanobacteria Synechococcus PCC 6301 and PCC 7942. Studies of
      mutants indicated that in the absence of IdiA mainly photosystem II becomes
      damaged, suggesting that the major function of IdiA is in Mn and not Fe
      metabolism (Michel et al. 1996, Microbiology 142: 2635-2645). To further
      elucidate the function of IdiA, the immunocytochemical localization of IdiA in
      the cell was examined. These investigations provided evidence that under mild Fe
      deficiency IdiA is intracellularly localized and is mainly associated with the
      thylakoid membrane in Synechococcus PCC 6301. The protein became distributed
      throughout the cell under severe Fe limitation when substantial morphological
      changes had already occurred. For additional verification of a preferential
      thylakoid membrane association of IdiA, these investigations were extended to the
      thermophilic Synechococcus elongatus. In this cyanobacterium Mn deficiency could
      be obtained more rapidly than in the mesophilic Synechococcus PCC 6301 and PCC
      7942, and the thylakoid membrane structure proved to be more stable under
      limiting growth conditions. The immunocytochemical investigations with this
      cyanobacterium clearly supported a thylakoid membrane association of IdiA. In
      addition, evidence was obtained for a localization of IdiA on the cytoplasmic
      side of the thylakoid membrane. All available data support a function of IdiA as
      an Mn-binding protein that facilitates transport of Mn via the thylakoid membrane
      into the lumen to provide photosystem II with Mn. A possible explanation for the
      observation that IdiA was not only expressed under Mn deficiency but also under
      Fe deficiency is given in the discussion.

PMID- 9599806
TI  - Evidence for secretion of vacuolar alpha-mannosidase, class I chitinase, and
      class I beta-1,3-glucanase in suspension cultures of tobacco cells.
AB  - We have investigated the possibility that vacuolar proteins can be secreted into
      the medium of cultured cells of Nicotiana tabacum L. Time-course and balance
      sheet experiments showed that a large fraction, up to ca. 19%, of vacuolar alpha
      mannosidase (EC 3.2.1.24) and vacuolar class I chitinase (EC 3.2.1.14) in
      suspension cultures accumulated in the medium within one week after subculturing.
      This effect was most pronounced in media containing 2,4-dichlorophenoxyacetic
      acid (2,4-D). Under comparable conditions only a small fraction, 1.8-5.1% of the
      total protein and ca. 1% of malate dehydrogenase (EC 1.1.1.37), which is
      localized primarily in the mitochondria and cytoplasm, accumulated in the medium.
      Pulse-chase experiments showed that newly synthesized vacuolar class I isoforms
      of chitinase and beta-1,3-glucanase (EC 3.2.1.39) were released into the medium.
      Post-translational processing, but not the release of these proteins, was delayed
      by the secretion inhibitor brefeldin A. Only forms of the proteins present in the
      vacuole, i.e. mature chitinase and pro-beta-1,3-glucanase and mature beta-1,3
      glucanase, were chased into the medium of tobacco cell-suspension cultures. Our
      results provide strong evidence that vacuolar alpha-mannosidase, chitinase and
      beta-1,3-glucanase can be secreted into the medium. They also suggest that
      secretion of chitinase and beta-1,3-glucanase might be via a novel pathway in
      which the proteins pass through the vacuolar compartment.

PMID- 9599807
TI  - The membrane potential of Arabidopsis thaliana guard cells; depolarizations
      induced by apoplastic acidification.
AB  - The apoplastic pH of guard cells probably acidifies in response to light, since
      light induces proton extrusion by both guard cells and epidermal leaf cells. From
      the data presented here, it is concluded that these apoplastic pH changes will
      affect K+ fluxes in guard cells of Arabidopsis thaliana (L.) Heynh. Guard cells
      of this species were impaled with double-barrelled micro-electrodes, to measure
      the membrane potential (Em) and the plasma-membrane conductance. Guard cells were
      found to exhibit two states with respect to their Em, a depolarized and a
      hyperpolarized state. Apoplastic acidification depolarized Em in both states,
      though the origin of the depolarization differed for each state. In the
      depolarized state, the change in Em was the result of a combined pH effect on
      instantaneously activating conductances and on the slow outward rectifying K+
      channel (s-ORC). At a more acidic apoplastic pH, the current through
      instantaneously activated conductances became more inwardly directed, while the
      maximum conductance of s-ORC decreased. The effect on s-ORC was accompanied by an
      acceleration of activation and deactivation of the channel. Experiments with acid
      loading of guard cells indicated that the effect on s-ORC was due to a lowered
      intracellular pH, caused by apoplastic acidification. In the hyperpolarized
      state, the pH-induced depolarization was due to a direct effect of the apoplastic
      pH on the inward rectifying K+ channel. Acidification shifted the threshold
      potential of the channel to more positive values. This effect was accompanied by
      a decrease in activation times and an increase of deactivation times, of the
      channel. From the changes in Em and membrane conductance, the expected effect of
      acidification on K+ fluxes was calculated. It was concluded that apoplastic
      acidification will increase the K(+)-efflux in the depolarized state and reduce
      the K(+)-influx in the hyperpolarized state.

PMID- 9599808
TI  - Glutamine synthetase isoenzymes, oligomers and subunits from hairy roots of Beta
      vulgaris L. var. lutea.
AB  - A cytosolic and a plastidic isoenzyme of glutamine synthetase (GS; EC 6.3.1.2)
      were separated from hairy roots of Beta vulgaris L. var. lutea. The predominant
      activity was that of cytosolic GS 1; the relative proportion of plastidic GS 2
      activity changed, however, depending on the growth conditions. Maximum activity
      of both isoenzymes was measured after growth with NO3- as the major N-source.
      Growth with NH4+ as the sole N-source or growth in constant darkness resulted in
      a significant decrease in GS 1 activity, whereas GS 2 activity was much less
      effected and thus contributed as much as 25% of total root GS activity. The
      isoenzymes GS 1 and GS 2 were active both in the octameric and tetrameric states.
      Both oligomers of GS 2 and octameric GS 1 were active under all growth conditions
      applied whereas tetrameric GS 1 was not active when the roots were grown under
      light-dark changes with NO3- as the major N-source. The molecular masses of the
      subunits were identical for both isoenzymes. Glutamine synthetase 1 was composed
      of up to four different 38-kDa subunits and two different 41-kDa subunits; GS 2
      was assembled from one type of 38-kDa subunit and one type of 41-kDa subunit. The
      GS 2 subunits were most probably identical to two of the GS 1 subunits. The
      subunit composition of GS 1, but not of GS 2, changed depending on the growth
      conditions of the roots. Changes in GS 1 subunit composition were correlated with
      changes in GS 1 activity. The different growth conditions induced the specific
      assembly of different GS 1 isoenzymes which could, however, not be separated by
      anion-exchange chromatography but became evident only after two-dimensional
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

PMID- 9599809
TI  - A maize FK506-sensitive immunophilin, mzFKBP-66, is a peptidylproline cis-trans
      isomerase that interacts with calmodulin and a 36-kDa cytoplasmic protein.
AB  - A member of a eukaryotic gene superfamily, encoding a peptidylproline cis-trans
      isomerase (rotamase) has been isolated from a maize (Zea mays L. A69Y+) endosperm
      cDNA library. The maize sequence (mzFKBP-66) encodes a 66-kDa polypeptide most
      closely related to the subclass of rotamases which bind an immunosuppressive
      drug, FK506, (termed FK506-binding proteins FKBPs), and possesses four tandem
      copies of the FKBP-like binding domain. The sequence mzFKBP-66 is expressed
      ubiquitously in the maize plant, and the protein encoded is present in both
      cytosolic and nuclear compartments within the cell. Both the native mzFKBP-66 and
      a recombinant protein overexpressed in Escherichia coli showed peptidylproline
      cis-trans-isomerase (PPIase) activity at rates comparable to those reported for
      mammalian immunophilins. This activity was also sensitive to inhibition by FK506.
      Immunoaffinity chromatography using anti-mzFKBP66 demonstrated an association of
      the protein with an unknown 36-kDa polypeptide, and affinity chromatography of
      mzFKBP-66 on calmodulin-agarose beads indicated the presence of a calmodulin
      binding site. The existence of mzFKBP-66-associated proteins suggests that plant
      immunophilins may act as part of multicomponent complexes, as has been shown for
      other representatives of this class of enzyme.

PMID- 9599810
TI  - Ethical considerations in contemporary medicine.
AB  - Numerous benefits brought along by the impressive technological progress of the
      contemporary world are also accompanied by potential hazards of dehumanization of
      life. As neither medicine has been skipped over by the technological progress,
      there is a risk for the physician to become dependent on it rather than master
      it. Therefore, there is the risk of deprivation of medical ethics norms, ever
      more frequently transforming the patient's position of the subject of medical
      activities into the position of an object. This pending risk is especially
      present in surgery, a medical discipline characterized by the highest
      technological and technical differentiation. If the surgeon is to preserve high
      ethical standards in his work, he should strictly follow the basic medical ethics
      norm, that proclaim full respect of the patient's will, forbid doing harm to the
      patient, and point to equity and compassion on providing medical aid. These
      ethical norms should be respected not only on performing surgical procedures, but
      also on making indications for the procedure. The future development of medicine
      and surgery, with a substantial impact of new, technical and technological
      advances, will open new, presently unknown ethical issues. All this will require
      through sociophilosophical and humane-ethical considerations in order to preserve
      the basic medical ethics norms warranting humaneness and ethics of medicine.

PMID- 9599811
TI  - Epidemiologic, ecologic and clinical characteristics of Lyme borrelliosis in
      northwest Croatia.
AB  - Investigated were the epidemiologic, ecologic and clinical characteristics of
      Lyme borreliosis in northwest Croatia. In a seroepidemiologic study, human sera
      were analyzed by indirect immunofluorescent assay (IFA), and ten out of 134 serum
      samples were positive for B. burgdorferi antibodies. In a seroepizootiologic
      study, wildlife and domestic animals were tested by inhibition ELISA. Antibodies
      to B. burgdorferi were found in nine out of 42 roe deer sera, and in three out of
      nine hare sera. Sera of wild boars (n = 10), cattle (n = 103), and dogs (n = 13)
      were negative for antibodies to B. burgdorferi. The presence of Borrelia
      burgdorferi sensu lato was assessed in ixodes ricinus ticks in the Lyme
      borreliosis endemic region of northwest Croatia. Ticks (n = 123) were collected
      at five-different locations and analyzed by polymerase chain reaction (PCR).
      Borrelia burgdorferi sensu lato DNA was detected in 56 out of 124 ticks (45%).
      Four genomic groups were identified by genotyping: B. afzelii (n = 26), B.
      garinii (n = 5), VS116 group (n = 5), and Borrelia burgdorferi sensu stricto (n =
      1). Mixed infections of B. afzelii with VS116 group (n = 10), and B. afzelii with
      Borrelia burgdorferi sensu stricto (n = 1) were also detected. Eight ticks
      contained B. burgdorferi sensu lato that could not be typed, indicating the
      possible existence of a specific genomic group of B. burgdorferi sensu lato in
      northwest Croatia. Sex distribution of Lyme borreliosis patients in northwest
      Croatia showed a slight preponderance of the female gender and prevalence of the
      working active age range of 20 to 50 years. The persons who periodically visit
      the landscape, are most commonly affected, whereas those with an increased risk
      of tick bites are considerably less frequently involved. The most frequent
      clinical manifestation of Lyme borreliosis in northwest Croatia is erythema
      migrans with 46%, followed by neurologic manifestations, particularly peripheral
      neuritis, with 32%. The rest of clinical manifestations in stage II and III of
      Lyme borreliosis are very rarely recorded. The presence of B. afzelii and B.
      garinii in the highest percentage is in agreement with the local occurrence of
      cutaneous and neurologic manifestations of Lyme borreliosis. The presence of
      VS116 group in ticks from northwest Croatia in this and other studies in some
      European countries may indicate that VS116 group is well established in the
      European ixodes ricinus ticks. The role of the VS116 group in the etiology of
      Lyme borreliosis remains to be clarified.

PMID- 9599812
TI  - A model of in vivo dosimetry and quality assurance analysis of total body
      irradiation in Zagreb.
AB  - The aim of the study was to develop a systemic and simple method for
      determination of midplane dose factors and lung correction factors, suitable for
      semiconductor 60-Co total body irradiation (TBI) in vivo dosimetry, based on
      input (entrance) and output (exit) dose readings. A theoretical model of
      anthropomorphic phantoms of cylindrical ellipsoid shape made it possible to
      generalize the applicability to any individual case of the real patient's data.
      Also, the quality assurance analysis of dosimetric results of 230 patients who
      had undergone TBI during a 10-year period, was performed. The ratio of the mean
      measured dose values for all locations in all patients and stated dose (12.45 Gy
      in 3 days, 3 fractions) was 0.998, SD 0.033. The upper limit of the total
      combined uncertainty of TBI midplane absorbed dose, including all locations and
      all sources of error, amounted to 9.4%.

PMID- 9599813
TI  - Infection with Helicobacter pylori and long-term use of non-steroidal
      antiinflammatory drugs.
AB  - The use of nonsteroidal anti inflammatory drugs (NSAID) is associated with an
      increased risk of peptic ulcer and of ulcer complications. However, the relation
      between Helicobacter pylori infection and gastroduodenal damage associated with
      NSAID use is unclear. This study investigated the prevalence of Helicobacter
      pylori infection in patients with arthritis (n = 85) taking NSAID, trying to find
      out whether the patients taking NSAID and infected with H. pylori were more
      likely to have dyspepsia, mucosal damage or chronic active gastritis than those
      without H. pylori infection. H. pylori was identified by biopsy, rapid urease
      test and histologic test. Dispeptic symptoms were assessed according to a
      standardized questionnaire. Gastroduodenal mucosal damage was graded
      endoscopically (using a modified Lanza scale) and the diagnosis of chronic
      gastritis was based on the histologic criteria of the Sydney system. The
      frequency of H. pylori infection was found to increase with age. No statistically
      significant difference was observed in the presence of damage to gastroduodenal
      mucosa between the patients with and without H. pylori infection. H. pylori
      infection was found to be associated with an increased frequency and severity of
      dyspeptic symptoms in patients with arthritis taking long-term NSAID. Chronic
      active gastritis was only present in patients with H. pylori infection. H. pylori
      infection was shown to be associated with an increased frequency and severity of
      dyspeptic symptoms in patients with arthritis on long-term NSAID therapy, without
      causing an increased damage to gastroduodenal mucosa.

PMID- 9599814
TI  - Anxiety in a large group.
AB  - Anxiety in a large group is a phenomenon much written about, but always as a
      subjective experience of the therapist and patients. Large group with its
      regressive situation stimulates the occurrence of archaic defense mechanisms,
      which gives the leader a special role as one who can influence, with his
      interventions, the intensity of anxiety. In order to prove the hypothesis of
      higher anxiety in a large group than in median and small groups, the authors
      measured the level of anxiety at the beginning and at the end of each of ten
      consecutive large group sessions.

PMID- 9599815
TI  - QT interval as a marker of venous reactivity in dialysis patients.
AB  - Fourteen patients (7 females and 7 males, mean age 51.9 +/- 11.6 years) were
      studied to find out whether there is a connection between the QTc interval (a
      diagnostic tool for evaluating autonomic neuropathy) and venous reactivity in
      uremics on chronic hemodialysis. The QT interval was measured using standard lead
      II as reference, corrected for heart rate, and designed QTc. Venous reactivity
      was measured by the so-called venoconstriction test. Pressure changes inside the
      vein were obtained by injection of 2 micrograms of noradrenaline, and expressed
      in venoconstrictive units (VCU). The mean QTc was 445.7 +/- 36.9 ms. The mean
      venous tone response was 2130.9 +/- 1435.5 VCU. There was a significant
      correlation between the QTc interval and venous reactivity to catecholamine (r =
      0.565, P = 0.03). It is concluded that the QTc interval may be used as a marker
      of venous tone reactivity, suitable for everyday clinical practice. Furthermore,
      the magnitude of this reactivity possibly represents either the end-organ or
      peripheral sympathetic impairment.

PMID- 9599816
TI  - Dietary fiber and retrograde starch.
AB  - The history of the recognition of the importance of dietary fiber, their current
      classification into water-soluble and water-insoluble fiber, and lignin, a single
      non-carbohydrate fiber, and the physiologic role of dietary fiber, with
      particular reference to retrograde starch resistance to small intestine
      digestion, are briefly presented. Dietary fiber are highly hygroscopic, thus they
      greatly contribute to stool voluminosity by binding water, decrease the glycemic
      index, and exert a protective action, via an as yet unknown mechanism, against
      the occurrence of colon cancer. It should be added that some dietary fiber
      decrease the concentration of cholesterol in the blood, i.e. in the human body.
      The importance of the methodology used for NSP determination is underlined, since
      some methods determine only some of the polysaccharides, other also measure some
      other substances, whereas Englyst's method determines NSP only.

PMID- 9599817
TI  - Efficacy of therapeutic plasma exchange in specific renal disease.
AB  - Therapeutic plasma exchange (TPE) is a treatment modality used in a variety of
      disease states, some of which are characterized by renal involvement (i.e.,
      primary and secondary rapidly progressive glomerulonephritis, myeloma
      nephropathy, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome). The
      aim of this review was to summarize the results of clinical studies that
      evaluated TPE efficacy in some renal diseases, and to give general guidelines for
      treatment strategies in specific renal diseases.

PMID- 9599818
TI  - Pathophysiology of venous insufficiency during pregnancy.
AB  - Pregnancy is a risk factor for venous insufficiency. Up to 30 percent of women
      will develop venous insufficiency during their first pregnancy, and with each
      next pregnancy its prevalence is higher. Several pathophysiologic mechanisms are
      involved in the pathophysiology of venous insufficiency during pregnancy. The
      role of these mechanisms in the pathophysiology of venous insufficiency during
      pregnancy is still a point of discussion. Mechanical compression of enlarged
      uterus on pelvic veins was the first considered responsible for the occurrence of
      venous insufficiency during pregnancy. Soon, it was found that hormonal changes
      in pregnancy cause reduction in venous tone, and this reduction was postulated to
      be a major factor in pathophysiology of venous insufficiency. In a large number
      of subsequent studies both hypotheses were tested, being confirmed or rejected,
      but no consensus has been reached. This paper reviews current knowledge regarding
      pathophysiology of venous insufficiency during pregnancy, and discusses the
      possible role that some as yet uninvestigated mechanisms might have in it.

PMID- 9599819
TI  - Tuberculous peritonitis--a case report.
AB  - Tuberculosis continues to be a major health problem worldwide and, due to its
      systemic nature, its clinical presentation may be highly variable. The diagnosis
      may, therefore, be unduly delayed. A 67-year old male refugee was admitted to our
      Department with a diagnosis of intra-abdominal carcinomatosis. During
      hospitalization, tuberculous peritonitis was found to be the cause of his
      symptoms. Antituberculosis therapy was administered and the patient responded
      adequately, achieving total clinical remission. The importance of considering
      this polymorphous disease is emphasized.

PMID- 9599820
TI  - Congenital elevation of the scapula (Sprengel's deformity).
AB  - A case of Sprengel's deformity (congenital elevation of the scapula) in a 4-year
      old boy, with a major cosmetic defect and compromised shoulder function,
      especially on abduction, is presented. The boy was operated on by Green's
      technique, with excellent cosmetic and functional result. Although Woorward's
      operative technique has generally been preferred in the treatment for Sprengel's
      deformity, the result obtained showed Green's procedure to be a satisfactory
      choice in this patient.

PMID- 9599821
TI  - Are percutaneous transgastric biopsies using 14-, 16- and 18-G Tru-Cut needles
      safe? An experimental study in the rabbit.
AB  - We evaluated perforation, peritonitis and bleeding after 14-, 16-, 18-G Tru-Cut
      needles were passed through the stomach in an animal model. Insertions were
      performed on seven anaesthetized rabbits with 18-, 16- and 14-G needles
      simulating the clinical technique. Diluted contrast medium with methylene blue
      (60 mL) was administered through a nasogastric tube after the biopsy. Computed
      tomography (CT) scanning of the upper abdomen was performed 10 min after the
      insertion for leakage. The abdominal contents were inspected by laparotomy. There
      was no contrast medium leakage outside the gastrointestinal tract on CT images.
      Neither methylene blue nor other stomach content leakage was identified by
      laparotomy, even with manual squeezing. A tiny spot of blood was observed on the
      serosal surface of the stomach with the 18-G needle passes (five cases), whereas
      a relatively large haematoma was present with 14-G needle (four cases). Six of
      the rabbits survived and one died due to an inadvertant aortic injury. The
      results of the study show that transgastric route with an 18-G cutting needle can
      be used without fear of peritonitis and bleeding.

PMID- 9599822
TI  - Transient bone marrow oedema: a variant pattern of sacral insufficiency
      fractures.
AB  - A 71-year-old woman presenting with severe low back pain was found to have a
      large oval area of increased sacral uptake on Tc-99m MDP scan, with corresponding
      T1-hypointense and T2-hyperintense areas on magnetic resonance (MR) images,
      highly suggestive of malignancy. Open biopsies showed only callus formation. The
      patient responded clinically to conservative measures, with twice-repeated follow
      up Tc-99m MDP and MR scans documenting resolution of transient bone marrow
      oedema. We suggest that this form of marrow oedema represents a variant pattern
      of sacral insufficiency fractures.

PMID- 9599823
TI  - Magnetic resonance imaging of the supraspinatus tendon: the significance of
      signal intensity alterations at the 'critical zone'.
AB  - A pictorial essay of normal and abnormal appearances of the supraspinatus tendon
      is presented. An increased signal intensity within the supraspinatus tendon on
      short TE sequences is not necessarily abnormal. Increased signal seen within the
      tendon on modern magnetic resonance imaging (MRI) units is often due to a
      phenomenon known as the 'magic angle' effect. Only when supraspinatus tendon
      signal intensity is greater than that of muscle on long TE (T2) sequences should
      it be considered to be abnormal. The physical basis for the magic angle effect is
      outlined and a pictorial essay demonstrating the practical implications of this
      effect is presented. A comparison is made to signal intensity changes seen with
      partial and complete tears of the supraspinatus tendon. Correlation is made with
      important morphologic features of partial or complete tears.

PMID- 9599824
TI  - Allergic reactions to oral iodinated contrast agents: reactions to oral contrast.
AB  - Allergic reactions can occur with virtually all substances used in medicine.
      Recently there has been increasing recognition that iodinated oral contrast
      agents (oral contrast) used in radiology are also capable of inducing an allergic
      response. Fortunately these are rarely life-threatening. This paper discusses
      three cases of mild reactions to oral iodinated contrast (all for computed
      tomography (CT) scans). The Australian experience of these agents is also
      reviewed.

PMID- 9599825
TI  - Assessment of pelvic stabilization devices for improved field reproducibility.
AB  - The aim of this study was to evaluate the improvement in patient comfort and
      field positional accuracy provided by a new pelvic stabilization system when
      delivering multiple field radiotherapy to the pelvis. The Pelvic Cradle (BEHTS
      Manufacturing, Brisbane, Qld, Australia) is a stabilization device that provides
      reproducible patient positioning and levelling. Ninety patients were randomized
      into three groups. The first group was treated using the Pelvic Cradle, the
      second group was treated using current stabilization practices, and the third
      group was treated using the Pron Pillo (Chattanooga Pharmacal Company, USA) and
      current stabilization practices. Port films were assessed for field displacement
      in the lateral and cranio-caudal directions. A patient survey was used to
      evaluate the patient's perception of comfort while receiving treatment. When
      compared to the control group, the pelvic cradle group demonstrated a 48%
      improvement in the mean lateral deviation from 3.8 mm to 2.0 mm (P < 0.001) and a
      36% improvement in the mean cranio-caudal deviation from 3.9 mm to 2.5 mm (P <
      0.001). The Pelvic Cradle was found to provide an improved level of field
      positional accuracy while maintaining patient comfort.

PMID- 9599826
TI  - Primary non-Hodgkin's lymphoma of the uterine cervix: case report of long-term
      survival of two patients treated with surgery and radiotherapy.
AB  - Two patients with Stage 1EA primary non-Hodgkin's lymphoma of the uterine cervix
      were treated by surgery and radiotherapy in 1986 and 1987. On follow-up, over a
      period of 10 years, both are well and remain free of recurrence.

PMID- 9599827
TI  - Magnetic resonance image detection of coincidental sphenoid sinus aspergillosis
      and pituitary microadenoma: a potential surgical disaster.
AB  - While localizing the microadenoma in a patient with Cushing's disease on magnetic
      resonance imaging (MRI), fungal granuloma of the sphenoid sinus was
      coincidentally detected. This helped in the proper management of sphenoidal
      disease before undergoing trans-sphenoidal removal of the microadenoma, thus
      averting the possible catastrophe of direct intracranial spread of aspergillus
      infection.

PMID- 9599828
TI  - Complications of epilepsy and a ruptured pyonephrosis: radiology to the rescue in
      the Brooks murder case.
AB  - A woman and her lover were accused of murdering the woman's husband. Five weeks
      after fracture/dislocations of both shoulders and a central fracture/dislocation
      of the right hip were diagnosed the woman's husband died of septicaemia
      consequent on a ruptured infected hydronephrosis. The shoulder and hip injuries
      and the ruptured hydronephrosis were attributed to a beating with a blunt
      instrument. A review of the medical records of the deceased, particularly his
      radiological examinations, led the authors to conclude that his joint injuries
      and ruptured kidney were not due to the alleged assault. The joint injuries were
      the consequence of epileptic seizures and the ruptured kidney was also due to
      natural causes. These medical opinions provided evidence that led to acquittal of
      the accused.

PMID- 9599829
TI  - Retroperitoneal ancient schwannoma: review of clinico-radiological features.
AB  - A case is reported here of an ancient schwannoma in the retroperitoneum. The
      findings of abdominal ultrasound and CT in a patient with a retroperitoneal
      ancient schwannoma are presented, and the clinical and radiological features of
      this unusual tumour are reviewed. The presence of a large, well-delineated
      complex cystic mass in the deep soft tissues should raise the possibility of an
      ancient schwannoma. It is important to recognize these tumours as benign with
      excellent prognosis so as to avoid unnecessary radical surgery.

PMID- 9599830
TI  - Spontaneous intramural haematoma of the oesophagus: CT and MRI appearances.
AB  - A 64-year-old man with history of ischaemic heart disease and coronary artery
      bypass graft surgery, but no history of peptic ulcer or liver disease, presented
      with retrosternal pain and coffee-ground vomitus. Endoscopy revealed a long
      column of bluish discolouration with normal mucosa interpreted as a grade IV
      oesophageal varix. Computed tomography showed a non-enhancing low-density
      submucosal columnar lesion in the mid- and lower oesophagus consistent with a
      submucosal haematoma. This resolved on follow-up at 10 days. The magnetic
      resonance features of intermediate signal intensity on T1-weighted images and
      hyperintense signal on T2-weighted images of this lesion are also highlighted.

PMID- 9599831
TI  - Dysphagia: a rare presentation of tuberculous mediastinal lymphadenitis.
AB  - Mediastinal lymphadenitis as the only presentation of adult tuberculosis is rare.
      Rarer still is dysphagia as the only presenting symptom of mediastinal
      tuberculous lymphadenitis. Here is the report of such a case.

PMID- 9599832
TI  - Diffuse panbronchiolitis: case report and review of the literature.
AB  - Diffuse panbronchiolitis is an uncommon disease of unknown aetiology mainly
      occurring in Asian races. Treatment with erythromycin acting through unclarified
      mechanisms is promising and may improve the poor prognosis currently associated
      with the disease. A case is presented illustrating how the imaging features of
      the disease, particularly on high-resolution computed tomography, may be used to
      support a diagnosis suggested on clinical grounds.

PMID- 9599833
TI  - Pedunculated hepatic haemangioma with arterioportal shunt: treated with angio
      embolization and surgery.
AB  - A case of symptomatic cavernous haemangioma of the liver with an unusual arterio
      portal shunting, which was treated by pre-operative angiographic embolization, is
      described. The arterio-portal shunting has been reported previously in only two
      cases.

PMID- 9599834
TI  - Inverted Y ureter anomaly and associated distal yo-yo phenomenon.
AB  - Duplication of the distal ureter is a very rare anomaly. A case is reported here
      in which the lower ectopic limb of the duplicated distal ureter presents with a
      ureterocele, and shows a different pattern of backflow.

PMID- 9599835
TI  - Endometrial adenosarcoma with adjuvant tamoxifen therapy for primary breast
      carcinoma.

PMID- 9599836
TI  - Renal metastasis from squamous cell carcinoma of the lung.
AB  - Symptomatic renal metastases from primary malignancy elsewhere in the body is an
      uncommon feature in disseminated cancer. Postmortem diagnosis is more frequent. A
      case is reported here of a patient with renal metastasis from lung carcinoma who
      presented with haematuria.

PMID- 9599837
TI  - Bilateral subacromial bursitis with macroscopic rice bodies: ultrasound, CT and
      MR appearance.
AB  - The radiological findings of ultrasound, CT and MR of a case of bilateral
      subacromial bursitis with macroscopic rice bodies is described. The previous
      literature is also reviewed.

PMID- 9599838
TI  - Incidental computed tomography diagnosis of a giant oesophageal leiomyosarcoma.
AB  - Leiomyosarcoma of the oesophagus is a very unusual tumour; only 53 cases have
      been reported in the English-language literature. A case is reported here of a
      patient with a giant leiomyosarcoma, without any symptoms of dysphagia. The
      diagnosis was made incidentally during CT examination of the chest for detection
      of possible pulmonary metastases from a coexisting carcinoma of the bladder. This
      was confirmed by a barium swallow, oesophagoscopy and tissue diagnosis. The
      literature pertaining to this most uncommon tumour is reviewed.

PMID- 9599839
TI  - Miliary tuberculosis: a complication of intravesical BCG treatment.

PMID- 9599840
TI  - A simple percutaneous inserter for radiopaque gold seeds used in radiotherapy
      treatment planning.
AB  - Percutaneous insertion of a radiopaque marker is an important technique used in
      radiotherapy planning for both external-beam and brachytherapy. It is of
      particular importance in the oral cavity. We describe the construction and use of
      a simple inserter for 'cold' gold seeds manufactured from a commercially
      available Becton Dickinson Brand 5-mL disposable syringe and a Becton Dickinson
      Brand 18 G 1 1/2 TW (1.25 x 38 mm) hypodermic needle.

PMID- 9599841
TI  - Defining involved field (IF) radiotherapy in Hodgkin's disease.

PMID- 9599842
TI  - Artificial urinary sphincters are resistant to radiotherapy.

PMID- 9599843
TI  - A postmodern public health?

PMID- 9599844
TI  - Hepatitis C, prisons, and public health.

PMID- 9599845
TI  - Is the eradication of donovanosis possible in Australia?

PMID- 9599846
TI  - Pertussis re-emerging: who is responsible?

PMID- 9599847
TI  - Poverty and health: exploring the links between financial stress and emotional
      stress in Australia.
AB  - The links between poverty and health have been investigated in a number of
      independent studies, as well as by the Poverty Commission in the 1970s and, more
      recently, the National Health Strategy. However, much of the poverty research
      suffers from the lack of detailed information on health status, while the work
      conducted in the public health sphere has used rather rudimentary poverty
      measures. The research reported here attempts to overcome these limitations by
      using unit record data from two national household surveys conducted by the
      Australian Bureau of Statistics in 1990. Together, these two data sets contain an
      enormous amount of detailed information on household incomes and the health
      status of individuals. Data from the two surveys are combined in a way which
      allows the links between poverty and health to be explored in greater detail than
      has hitherto been possible in Australia. Analysis of the integrated data set
      focuses on the links between poverty and several measures of stress-related poor
      health. The results from a variety of different methods point to the existence of
      significant differences between the reported incidence of stress of those whose
      incomes place them either side of a poverty threshold. The size of the
      statistical association between poverty and stress is of both numerical and
      statistical significance, although further work, preferably using longitudinal
      data, is needed on the important issues of causation.

PMID- 9599848
TI  - An attempt to swindle nature: press anti-immunisation reportage 1993-1997.
AB  - There is some evidence that low childhood immunisation rates in Australia may be
      attributed partly to parental antipathy toward immunisation. The anti
      immunisation movement is becoming more organised in its efforts to lobby against
      childhood immunisation, while the lessening of the public's exposure to the
      effects of vaccine-preventable disease has provided a climate ripe for such a
      lobby to have a disproportionate influence on parents. Forty months of Australian
      print media coverage of immunisation were reviewed for anti-immunisation
      arguments and their underlying ideological subtexts. Of 2440 articles about
      childhood immunisation, 115 (4.7 per cent) contained statements opposing
      immunisation. Eight subtexts that referenced wider discourses about medicine, the
      state and the body dominated anti-immunisation discourse (cover-up; excavation of
      the facts; unholy alliance for profit; towards totalitarianism; us and them;
      vaccines as poisonous chemical cocktails; vaccines as cause of idiopathic ills;
      and back to nature). Attempts to redress claims made against immunisation must
      not only address specific claims about vaccine efficacy and safety but be
      grounded in a reframing of the ideological appeals that currently frame the
      contents of anti-immunisation discourse.

PMID- 9599849
TI  - The Australian mortality decline: all-cause mortality 1788-1990.
AB  - This review describes the Australian decline in all-cause mortality, 1788-1990,
      and compares this with declines in Europe and North America. The period until the
      1870s shows characteristic 'crisis mortality', attributable to epidemics of
      infectious disease. A decline in overall mortality is evident from 1880. A
      precipitous fall occurs in infant mortality from 1900, similar to that in
      European countries. Infant mortality continues downward during this century
      (except during the 1930s), with periods of accelerated decline during the 1940s
      (antibiotics) and early 1970s. Maternal mortality remains high until a
      precipitous fall in 1937 coinciding with the arrival of sulphonamide. Excess
      mortality due to the 1919 influenza epidemic is evident. Artefactual falls in
      mortality occur in 1930, and for men during the war of 1939-1945. Stagnation in
      overall mortality decline during the 1930s and 1945-1970 is evident for adult
      males, and during 1960-1970 for adult females. A decline in mortality is
      registered in both sexes from 1970, particularly in middle and older age groups,
      with narrowing of the sex differential. The mortality decline in Australia is
      broadly similar to those of the United Kingdom and several European countries,
      although an Australian advantage during last century and the first part of this
      century may have been due to less industrialisation, lower population density and
      better nutrition. Australia shows no war-related interruptions in the mortality
      decline. Australian mortality patterns from 1970 are also similar to those
      observed in North America and European countries (including the United Kingdom,
      but excluding Eastern Europe.

PMID- 9599850
TI  - The Australian mortality decline: cause-specific mortality 1907-1990.
AB  - This review describes the changes in composition of mortality by major attributed
      cause during the Australian mortality decline this century. The principal
      categories employed were: infectious diseases, nonrheumatic cardiovascular
      disease, external causes, cancer, 'other' causes and ill-defined conditions. The
      data were age-adjusted. Besides registration problems (which also affect all
      cause mortality) artefacts due to changes in diagnostic designation and coding
      are evident. The most obvious trends over the period are the decline in
      infectious disease mortality (half the decline 1907-1990 occurs before 1949), and
      the epidemic of circulatory disease mortality which appears to commence around
      1930, peaks during the 1950s and 1960s, and declines from 1970 to 1990 (to a rate
      half that at the peak). Mortality for cancer remains static for females after
      1907, but increases steadily for males, reaching a plateau in the mid-1980s
      (owing to trends in lung cancer); trends in cancers of individual sites are
      diverse. External cause mortality declines after 1970. The decline in total
      mortality to 1930 is associated with decline in infection and 'other' causes.
      Stagnation of mortality decline in 1930-1940 and 1946-1970 for males is a
      consequence of contemporaneous movements in opposite directions of infection
      mortality (decrease) and circulatory disease and cancer mortality (increase). In
      females, declines in infections and 'other' causes of death exceed the increase
      in circulatory disease mortality until 1960, then stability in all major causes
      of death to 1970. The overall mortality decline since 1970 is a consequence of a
      reduction in circulatory disease, 'other' cause, external cause and infection
      mortality, despite the increase in cancer mortality (for males).

PMID- 9599851
TI  - Coverage of cancer patients by hospice services, South Australia, 1990 to 1993.
AB  - A population-based observational study of South Australian cancer patients was
      used to identify: the level of coverage of cancer patients by hospice services;
      the types of patients who miss out on hospice care; and the place of death of
      hospice and other cancer patients. We reviewed patients who died in 1990 and 1993
      using the Central Cancer Registry database together with an identifier of hospice
      involvement. In 1990, 56 per cent of cancer patients who died had care from a
      hospice service, and this proportion increased to 63 per cent in 1993. Elderly
      patients, rural residents and those with a haematological malignancy were less
      likely than other patients to receive care from a hospice service, while patients
      aged between 40 and 60 years, longer survivors and those born in the United
      Kingdom and Europe were more likely to receive hospice care. Hospice involvement
      increased significantly between 1990 and 1993 for patients who died at home (59
      to 73 per cent), in nursing homes (20 to 45 per cent), private hospitals (33 to
      52 per cent) and public hospitals (48 to 55 per cent), but the proportion of
      patients with hospice involvement who died in country hospitals remained at 45
      per cent. The increase in hospice coverage of terminal cancer patients reflects
      the continued integration of hospice care into the mainstream of health care
      delivery. The types of patients who miss out on hospice services should be given
      special consideration in the future planning of terminal care services.

PMID- 9599852
TI  - How common is domestic violence against women? The definition of partner abuse in
      prevalence studies.
AB  - We systematically reviewed studies of the prevalence of domestic violence.
      Selected overseas community studies were compared with all Australian prevalence
      studies found to be published. Twelve-month prevalence estimates of partner abuse
      in Australia varied from 2.1 per cent to 28.0 per cent, depending mainly on the
      definition of domestic violence used in each study. Implications of the lack of a
      precise definition result in varying operationalised definitions of partner
      abuse, from all types of violence in relationships (including a single minor
      violent incident), through to only those violent incidents that are classified as
      a crime. Recommendations for any future prevalence studies in this field include
      the need to collect frequency data which reflected the fact that partner abuse
      against women is a complex behavioural phenomenon involving emotional, physical
      and sexual abuse against a partner, not just simply physical incidents.

PMID- 9599853
TI  - Evaluation of antenatal smoking cessation programs for pregnant women.
AB  - Smoking during pregnancy has been linked to health problems, including the risk
      of low birthweight, preterm labour, spontaneous abortion and perinatal death. Two
      trials to investigate the efficacy of self-help materials were undertaken. During
      the first trial, a self-help booklet developed overseas was evaluated through a
      randomised controlled design to determine the effects of the booklet alone,
      compared with the booklet with midwife counselling for the women. We recruited
      217 women into the study and followed them up at 20 weeks' gestation to ascertain
      smoking cessation and to measure process variables. Smoking cessation rates were
      lower than expected, and process measures indicated that materials were not being
      used. A second trial was commenced after a comprehensive review of the materials
      with focus groups of pregnant women and one-to-one interviews of nurses and
      doctors. Trial 2 was based new materials, and used a magazine-style (smoking
      cessation) booklet designed by the focus groups. A total of 119 women were
      randomly allocated into the new-materials group or a usual-care group. The
      materials were well received, relevant and pertinent, and were used by the women.
      Smoking cessation rates at 20 weeks' gestation were biochemically validated and
      indicated that 9 per cent in the intervention group and none in the usual-care
      group had stopped smoking. The use of overseas programs needs to be approached
      with caution.

PMID- 9599854
TI  - Socioeconomic status and maternal cigarette smoking before, during and after a
      pregnancy.
AB  - Research suggests that cigarette use declines when women find out they are
      pregnant, increasing again after the birth. Pregnancy may provide many women with
      a substantial impetus to stopping smoking. Also, rates of smoking cessation and
      reduction may be class-related, with the highest socioeconomic-status groups
      manifesting higher rates of reduction. Using data from the Mater Hospital-
      University of Queensland Study of Pregnancy, we report family income related to
      rates of smoking before, during and after a pregnancy. Before becoming pregnant,
      45.9 per cent of women in the sample were smokers. This declined to 34.7 per cent
      of women at their first clinic visit. Rates of heavy smoking (20 or more
      cigarettes per day) had returned to earlier levels by the six-month (after birth)
      follow-up. Women in the lowest family-income group had the highest rates of
      cigarette use before, during and after their pregnancy. Of the lowest family
      income group, 8.4 per cent were heavy smokers before, during and after their
      pregnancy, compared with 2.8 per cent of women in the highest family-income
      group. Smoking cessation rates were highest in the highest family-income group
      (those who smoked least), but relapse rates after the birth were similar for all
      income groups. Arresting rates of smoking relapse by pregnant women should be
      seen as a major public health priority.

PMID- 9599855
TI  - Measuring the impact of conjugate vaccines on invasive Haemophilus influenzae
      type b infection in Western Australia.
AB  - Haemophilus influenzae type b (Hib) causes serious infections in 26-59 per
      100,000 non-Aboriginal Australian children under five years of age. Aboriginal
      children suffer much higher rates of infection (> or = 150 per 100,000), and at
      an earlier age, and have a greater risk of death and disability due to Hib
      infection. In 1992 and 1993, four conjugate Hib vaccines were introduced in
      Australia, and a nationally funded program of infant vaccination was begun in
      July 1993. This study aimed at evaluating the effectiveness of Hib vaccination in
      Aboriginal and non-Aboriginal children in Western Australia using a population
      based active surveillance system for non-Aboriginal children and a case control
      study for Aboriginal children. The incidence of invasive Hib disease in non
      Aboriginal children fell from 30.9 per 100,000 before vaccination was available
      to 6.3 per 100,000 in the second year after its introduction. The vaccine
      efficacy was estimated to be 80 per cent for Aboriginal children (odds ratio
      0.20, 95 per cent CI 0.01-2.76) and, after adjustment for confounders, 75 per
      cent (odds ratio 0.25, CI 0.02-3.66). Based on the adjusted value (75 per cent),
      and using a Bayesian approach, we estimate that the posterior probability was
      0.55 that the true vaccine efficacy is greater than 70 per cent, and 0.69 that
      the efficacy is greater than 50 per cent. We conclude that Hib vaccination is
      effective in preventing invasive Hib disease in Aboriginal and non-Aboriginal
      children in Australia.

PMID- 9599856
TI  - Weight-control practices of adults in a rural community.
AB  - Obesity is recognised as a significant public health problem, and health
      authorities are concerned with promoting a healthy weight for all adults.
      However, there is a paucity of data about community weight-control practices. We
      surveyed weight-control behaviour, strategies and goals in a population-based
      sample of 1342 adults living in rural Victoria. In addition to the 20 per cent of
      adults who were attempting to lose weight, 22 per cent were actively trying to
      maintain their present weight or to avoid weight gain. Those taking action for
      their weight most often did so for health-related reasons, and most of the
      strategies used were those recommended by health authorities. However, some
      adults, particularly women, adopted potentially unhealthy weight-control
      practices. One in four women whose weight was acceptable was trying to lose
      weight, and 14 per cent of women had a weight goal that was below the acceptable
      range. Conversely, 50 per cent of men had a weight goal higher than that
      currently considered acceptable. Additional research is required to assess more
      accurately the specific nature of community weight-control practices.

PMID- 9599857
TI  - Alcohol consumption and injury in Western Australia: a spatial correlation
      analysis using geographic information systems.
AB  - Geographic information systems technology was used to describe, in geographical
      terms, the nature and strength of the relationship in Western Australia between
      alcohol consumption and the rates of related injury: night-time assaults (10 p.m.
      to 6 a.m.); minor night-time road crashes (10 p.m. to 6 a.m.), weighted by
      traffic density; and hospital E-code (external-cause) morbidity, weighted by
      alcohol aetiologic fractions. The data were aggregated by five conventional state
      regions: northern, central, western, southern and Perth metropolitan. There was a
      general association, of equal significance for males and females, between
      estimated per capita alcohol consumption and the selected rates of injury in the
      five regions. However, the nature and strength of association between alcohol
      consumption and individual injury measures varied. Night-time assaults and
      hospital E-code morbidity were strongly, associated with consumption. Minor night
      time crashes had only a weak association. The variation in the relationship
      between alcohol consumption and injury suggests that prevention strategies need
      to take into account the particular drinking patterns and associated harm that
      occur in different regions of the state, and to develop a range of targeted
      responses. High rates of consumption and injury in most country areas support the
      need for greater regional prevention efforts.

PMID- 9599858
TI  - Clinical consultations in an aboriginal community-controlled health service: a
      comparison with general practice.
AB  - Clinical consultation at Danila Dilba, an Aboriginal community-controlled health
      service in Darwin, were compared with consultations in Australian general
      practice. We described 583 consultations, using a questionnaire based on the
      International Classification of Primary Care. The methods were similar to those
      of the Australian Morbidity and Treatment Survey (AMTS) of consultations in
      Australian general practice undertaken by the University of Sydney Family
      Medicine Research Unit. Compared with Australian general practice consultations,
      consultations with Danila Dilba were more complex: more young patients, more new
      patients, more home visits, more problems managed, more new problems and more
      consultations leading to emergency hospital admission. Skin infections, diabetes
      mellitus, chronic alcohol abuse, rheumatic heart disease (or rheumatic fever) and
      chronic suppurative otitis media were much more commonly managed at study
      consultations at Danila Dilba than at consultations with general practitioners in
      the AMTS. Nearly all patients saw an Aboriginal health worker first, and nearly
      half the consultations were with Aboriginal health workers alone. The results
      suggest possible limitations of fee-for-item Medicare funding of Aboriginal
      community-controlled health services compared with existing block grant funding.

PMID- 9599859
TI  - HIV-related discrimination: a survey of New South Wales general practitioners.
AB  - This study aimed to investigate the correlates of human immunodeficiency virus
      (HIV)-related discrimination among general practitioners. The survey, conducted
      in 1993-1994, covered a random sample of 878 general practitioners from six of
      the 12 New South Wales health areas, augmented by 44-general practitioners from
      the same areas who were antiretroviral drug prescribers. The response rate was 51
      per cent, and the final usable sample was 451. Variables examined were:
      demographic characteristics, the number of HIV-infected patients, personal
      contact with people living with HIV or AIDS, personal contact with homosexuals,
      the degree of anxiety about HIV or AIDS, and the degree of HIV-related
      discrimination. Discriminatory attitudes among general practitioners decreased as
      contact with HIV-infected patients (P < 0.001), other people living with HIV or
      AIDS (P < 0.001), and homosexuals (P < 0.001) increased. Anxiety about HIV or
      AIDS also decreased as contact increased (P < 0.001). Higher levels of anxiety
      were strongly associated with higher levels of HIV-related discrimination (P <
      0.001). The demographic correlates of discrimination among general practitioners
      were the same as those found in the wider population. The professional care of
      people living with HIV and AIDS was concentrated among a small number of general
      practitioners, many of whom were homosexual. Ten general practitioners were
      carrying extraordinarily high caseloads of over 200 HIV-infected patients each.
      Older, heterosexual and male general practitioners are an important target for
      education campaigns, and the professional care of people living with HIV or AIDS
      should be encouraged among a wider group of general practitioners.

PMID- 9599860
TI  - Older people's lives in the inner city: hazardous or rewarding?
AB  - An exploratory, qualitative study was used to investigate the social health needs
      of older residents of a low-income inner-Sydney area characterised by multiple
      social and environmental hazards. The research was conducted to inform the
      development by the South Eastern Sydney Area Health Promotion Unit of a strategy
      to promote the health, wellbeing and independence of older people. As part of a
      needs assessment process, the investigation focused on specific subgroups of the
      population believed to be highly disadvantaged and neglected. In-depth interviews
      were conducted with 40 residents aged 60 to 86 years who were recruited through
      community centres, service providers and neighbours. The interviews were
      supplemented by observational field notes. We describe key dimensions of the
      physical and social environment, the many hazards it presented to vulnerable
      elderly residents and the practices they adopted in meeting their everyday needs
      in relation to shopping, meals, mobility outside the home and social
      participation. The description is from the perspectives of residents themselves.
      Key factors discussed include the neighbourhood, housing, activities of daily
      living, safety and security, and social participation. We explore the
      implications of our findings for the development of effective public health
      practice. The environmental hazards, such as pedestrian safety and traffic
      management, affect the whole population and require interventions at government
      level. Others, such as inadequate hygiene and food storage facilities in rented
      premises, also require an approach at the level of public policy and
      environmental change, but need to be carefully targetted and implemented.

PMID- 9599861
TI  - Family health and health services utilisation in Belmont, Western Australia: a
      community case study.
AB  - This case study was designed to examine the self-defined health needs of families
      in one urban Western Australian community. We conducted 157 family interviews to
      examine the relationship between family sociodemographic variables and patterns
      of use of health services, which included services used within the previous 12
      months, and what the family needed and wanted from these services. Questions
      covered perceptions of health, family health concerns and the role of the family
      health guardian. Quantitative analysis included frequencies, cross-tabulations,
      chi-squared tests and multiple regression analysis. Open-ended responses were
      categorised and analysed for common themes. Approximately 80 per cent of
      participants had used one or more health services during the previous 12 months
      and, despite 35.9 per cent of families having at least one family member with a
      long-standing illness, disability or infirmity, most (82.1 per cent) considered
      the family healthy. The correlational analysis revealed several associations.
      Predictably, younger persons reported higher health ratings and older persons had
      more health concerns. Larger families reported better perceived levels of health.
      Higher utilisation rates were recorded for families with children, who tended to
      use the general practitioner for general care and medication, whereas one-parent
      families used hospital and specialist care more often, and 98.7 per cent reported
      satisfaction with services. What they needed and wanted from their health service
      providers was 'full disclosure' and 'not being talked down to', and for
      specialists especially to be approachable and impart information simply and
      honestly.

PMID- 9599862
TI  - Designing an evaluation for a multiple-strategy community intervention: the North
      Coast Stay on Your Feet program.
AB  - Evaluation of the North Coast Stay on Your Feet falls prevention program is
      described as a case study of a comprehensive evaluation design for multi
      strategic community interventions. Qualitative and quantitative methods were used
      to evaluate the program at formative, process and outcome levels. Formative
      evaluation used literature review, focus groups, mail-out and telephone survey
      methods to gather evidence from publications, older people, health workers, local
      business, media and government bodies. It included an analysis of demographic and
      hospital databases and identified incidence, causal pathways, knowledge,
      attitudes, behaviour, consequences and effectiveness of potential strategies.
      Process evaluation employed auditing, monitoring and telephone surveys to
      maintain an inventory of intervention activities and to track the reach of the
      program. Outcome evaluation involved a longitudinal study of intervention and
      control cohorts, surveyed before, during and after the intervention by telephone
      to monitor changes in knowledge, attitudes, risk and falls incidence. The survey
      instrument was designed for both formative and outcome evaluation, and analysis
      reflected the research design by incorporating repeat measures and adjusting for
      bias and confounding. Outcome validity was cross-checked via hospital admission
      rates. A novel, integrated framework for presenting inputs, activities and
      outcomes from all stages of the program is described. This framework facilitated
      feedback to stakeholders and enabled subsequent rapid adjustment of the
      intervention. Rigorous evaluation combined with clear presentation of findings
      helped to engender intersectoral support and obtain funding grants for extended
      implementation and evaluation. It also helped Stay on Your Feet to become a model
      for other falls prevention programs within Australia and internationally.

PMID- 9599863
TI  - Deliberate self-inflicted trauma: population demographics, the nature of injury
      and a comparison with patients who overdose.
AB  - Self-inflicted harm, whether by trauma or drug overdose, is not uncommon, and has
      important social consequences. This study was a retrospective record analysis of
      patients who presented to an emergency department after deliberate self-inflicted
      harm. Over the two-year study period, there were 175 self-inflicted trauma and
      441 overdose presentations. The self-inflicted trauma patients were a
      heterogeneous group and included patients who displayed suicide-related behaviour
      and behaviour not related to suicide. The self-inflicted traumatic injuries
      tended to be either relatively minor or potentially very serious. Lacerations to
      the upper limb were seen most frequently. The trauma and overdose groups were
      almost mutually exclusive populations and showed some significant differences.
      The trauma group was smaller, contained a significantly greater proportion of
      younger patients and males, presented more commonly in the late evening and early
      morning hours and ultimately received less psychiatric counselling. Research of
      this type has problems of underreporting and data bias. Prospective studies of
      self-inflicted trauma would improve the identification of patients after self
      harm and improve the understanding of the relationship between the patterns of
      injury psychiatric diagnosis and the long-term risk of future self-harm.

PMID- 9599864
TI  - Cost-effectiveness of measles outbreak intervention strategies.
AB  - In this study, we compared the likely cost-effectiveness of alternative
      strategies for controlling a school-based measles outbreak. The analysis involved
      assessing the expected costs and number of cases in a school-based outbreak of
      measles, with no intervention and with each of six control strategies. The
      marginal cost per case prevented ranged from $32.90 when only previously
      unvaccinated school children were offered vaccination to $6795 when vaccination
      was extended to the siblings of school children aged 6 to 12 months. This study
      provided further evidence of the cost-effectiveness of vaccination in outbreak
      control, and yielded useful information to inform control strategies in the event
      of a school-based outbreak. Decisions about which groups of children to aim at
      and whether to conduct school-based clinics will be influenced by local
      circumstances, particularly the baseline measles vaccination rate and the measles
      attack rate among infants.

PMID- 9599865
TI  - Resource requirements to develop a large, remote aboriginal health service: whose
      responsibility?
AB  - In 1994 the Commonwealth funded studies to establish and develop Aboriginal
      health services. One such study was undertaken in 1995 at Maningrida, Northern
      Territory: to identify the health-service needs of the population and consider
      community management structures; to identify Northern Territory expenditure for
      primary health care; and to provide a three- to five-year development budget.
      Approximately 2100 Aboriginal residents in the region used the service, including
      750 living on 24 outstations within 75 km. Nearly 40 per cent were aged under 15
      years. Childhood morbidity was high, with children under two averaging 1.4
      hospital admissions per year. The age pyramid reflected premature adult mortality
      from the third decade of life. Service providers identified inadequate staffing
      and infrastructure as barriers to service development. Community consultations
      emphasised the need for resident doctors, improved outstation services and aged
      and respite care, local training for Aboriginal health workers and housing for
      staff. These developments would require per capita primary health care
      expenditure ($872) to be doubled. Aboriginal people in remote areas are
      disadvantaged through Commonwealth Grants Commission funding formulae and lack of
      Medicare access. As the sole funding source, the Northern Territory spends over
      $1.83 million per year providing health services at Maningrida. Additionally, the
      study proposed that the Commonwealth spend $1.96 million a year over five years
      on staffing and infrastructure. Local Aboriginal organisations also agreed to
      allocate resources for health service development. Ineffective implementation,
      lack of clarification of government responsibilities and funding shortfalls
      remain barriers to developing remote Aboriginal health services.

PMID- 9599866
TI  - Ciguatera poisoning: an example of a public health challenge.
AB  - Ciguatera is a common form of fish poisoning, endemic in all nations of the
      Pacific region. Several thousand cases have been notified to Queensland
      authorities over a 10-year period. However, many cases remain undiagnosed and
      most go unreported. The public health implications include raising awareness of
      the condition, ensuring that ciguatera is considered in differential diagnosis
      and promoting better documentation and reporting.

PMID- 9599867
TI  - Universal hepatitis B vaccination: hospital factors influencing first-dose uptake
      for neonates in Darwin.
AB  - A universal neonatal hepatitis B vaccination program was introduced in the
      Northern Territory in 1990. We compared live births with vaccine usage to
      determine the uptake of the first dose of hepatitis B vaccine under this new
      policy and to identify hospital factors that influenced this rate. Attitudes and
      vaccine administration practices were determined through interviews, using
      standard questions with midwifery and paediatric nursing staff at both hospitals.
      Hepatitis B vaccines dispensed at Hospital A indicated a 96 per cent coverage of
      neonates in 1993 and 93 per cent in 1994. Vaccination at Hospital B indicated 71
      per cent coverage in 1993 and 77 per cent in 1994. Differences in vaccine uptake
      appeared to be influenced by the use of standing drug orders, the nursing staff's
      attitudes and knowledge, and misinformation among health professionals. Education
      programs for health professionals and parents need to be established before the
      introduction of a universal hepatitis B vaccination policy for it to be well
      accepted. Standing orders for hepatitis B vaccine in postnatal wards allow
      nursing staff to promote it and thus maximise coverage rates.

PMID- 9599868
TI  - Print material as a public health education tool.
AB  - Despite the widespread use of print materials in public health education, little
      is known about the costs and processes involved in developing these materials and
      their effectiveness in practice. We examined a sample of printed health education
      materials, using interviews and checklists. The most cost-effective processes for
      developing materials were not being used and the effectiveness of materials was
      rarely evaluated.

PMID- 9599869
TI  - New, or biased, evidence on water fluoridation?
AB  - The recent review, 'New evidence on fluoridation', by Diesendorf, Colquhoun,
      Spittle, Everingham and Clutterbuck (Aust N Z J Public Health 1997; 21: 187-90)
      claims a consistent pattern of evidence pointing to fluoride damaging bone, a
      negligible benefit in dental caries reduction from ingested fluoride, and any
      small benefit from fluoride coming from the action of fluoride at the tooth
      surface. Public health authorities are allegedly reluctant to pursue such
      evidence. In the interest of scholarly debate, invited by Diesendorf et al., this
      reaction paper examines six separate areas raised in the original paper:
      fluoridation and hip fracture; fluoridation and osteosarcomas; pre-eruptive and
      posteruptive benefits in dental caries reduction; fluoride ingestion; benefit in
      dental caries reduction for contemporary Australian children; and bias of health
      authorities and responsible science. Numerous examples of bias in the
      identification, selection and appraisal of the evidence on water fluoridation
      presented by Diesendorf et al. are developed. Further, this reaction paper puts
      forward both studies and appraisal indicating that water fluoridation should
      continue to be regarded as a safe and effective public health measure.

PMID- 9599870
TI  - Do media help or harm public health?

PMID- 9599871
TI  - Globalisation: what does 'intersectoral collaboration' mean?

PMID- 9599872
TI  - Subsidising Australian pseudoscience: is iridology complementary medicine or
      witch doctoring?

PMID- 9599873
TI  - Physical activity measurement in children.

PMID- 9599875
TI  - Gonorrhoea and syphilis in the Kimberley region.

PMID- 9599874
TI  - Fluoridation and bones: authors' response to critics.

PMID- 9599876
TI  - Specialisation makes progress.

PMID- 9599877
TI  - Who wants to be a specialist?
AB  - The UK has not developed the degree of limited practice which is common overseas
      and is now growing in Europe. However, changes in European legislation have
      brought about a recognition of these specialist disciplines within dentistry.

PMID- 9599878
TI  - Research in general dental practice.

PMID- 9599879
TI  - Prescription of methotrexate.

PMID- 9599880
TI  - Modifications of an immediate adhesive bridge using the natural tooth.

PMID- 9599881
TI  - Long-term restoration.

PMID- 9599882
TI  - Oral, cardiovascular and general health.

PMID- 9599883
TI  - Maxillofacial prosthodontics and reconstruction: a Canadian view.
AB  - A craniofacial osseointegration and maxillofacial prosthetic rehabilitation unit
      in Edmonton, Canada was visited by the author as part of a higher specialist
      training programme. The unit has an international reputation as a centre of
      excellence for the treatment of patients with head and neck abnormalities. The
      report examines the activities of the unit and how it achieves its 'patient
      centred' approach to care.

PMID- 9599884
TI  - Advances in periodontal diagnosis. 7. Proteolytic and hydrolytic enzymes link
      with periodontitis.
AB  - Biomarkers of periodontal disease activity may be obtained from potential
      proteolytic and hydrolytic enzymes of inflammatory cell origin. Studies that have
      sought to correlate these enzymes with periodontal disease activity are reviewed
      with special consideration given to collagenases, cysteine, aspartate and serine
      proteinases, beta-glucuronidase, arylsulphate, alkaline and acid phosphatases,
      myeloperoxidase, lysozyme and lactoferrin.

PMID- 9599885
TI  - The management of thermomechanically compacted gutta percha extrusion in the
      inferior dental canal.
AB  - Endodontic material inadvertently forced into the inferior dental canal during
      root-canal therapy can cause damage to the underlying nerve. The effect of toxic
      filling materials on nervous tissues has been well publicised, however, the
      thermal and pressure changes produced by chemically bland materials has not been
      adequately highlighted. In the case reported, thermoplasticised gutta percha was
      inadvertently introduced into the canal during endodontic treatment of a lower
      molar. Factors affecting the outcome are discussed and guidelines are presented
      for the management of such a case with reference to surgery against observation.

PMID- 9599886
TI  - How to avoid local anaesthetic toxicity.
AB  - Local anaesthetic overdose is not common in dental practice but can occur. In
      rare cases it can be fatal. Normally the use of good technique employing small
      amounts of solution limits toxicity. In addition, thorough medical history taking
      should forewarn the dentist of any patient who has experienced problems in the
      past and will also alert the operator to those few patients who exhibit
      idiosyncratic reactions. This article aims to offer practical advice to help
      avoid local anaesthetic toxicity.

PMID- 9599888
TI  - Integration of primary care dental and medical services: a three-year study.
AB  - OBJECTIVE: To develop and evaluate a model of integrated primary dental and
      medical care. DESIGN: 3-year prospective study. SETTING: A general dental
      practice and a general medical practice occupying the same building in Glasgow.
      INTERVENTION: Regular staff meetings, joint use of patient records systems and
      information derived from patient questionnaires. Dentistry was included in
      established screening programmes such as child health surveillance and care of
      elderly. Staff were encouraged to participate in joint work practices and joint
      consultations were carried out. MAIN OUTCOME MEASURES: Patient registration,
      avoidance of discrepancies in information, reduction of secondary referrals,
      joint work practices. RESULTS: The number of registered joint patients attending
      both medical and dental practices increased by 90%. The joint use of patient
      record systems avoided discrepancies in patient information which would have
      affected the quality of patient care. Including dentistry in child health
      surveillance and care of elderly screening programmes resulted in an increase in
      0-5 year olds registering with dentists from 36% to 68% (P < 0.001) and with > 75
      year olds from 47% to 71% (P < 0.001). Joint consultations reduced the need for
      secondary referrals. CONCLUSIONS: This model of health care demonstrated the
      potential for coordination and integration of functions between the dental team
      and the primary care team. Integrated primary dental and medical care requires
      attitudinal change in health care professionals and requires greater emphasis in
      education and training of health care professionals in the future.

PMID- 9599890
TI  - A public perception of access to NHS dentistry.
AB  - OBJECTIVE: To quantify the level of unmet dental access need which had been
      reported locally and to provide information about the perceived need for dental
      treatment with particular reference to those not registered for continuing NHS
      care. DESIGN: A postal survey of adults resident in Aylesbury Vale,
      Buckinghamshire was carried out toward the end of 1994. SUBJECTS AND METHODS:
      2000 adults aged between 35 and 54 years were randomly selected: RESULTS: A
      response rate of 68% matched well with the population under study. 16% of people
      were unable to access any regular dental care and this group had the highest
      treatment need, with more experience of broken fillings and toothache within the
      previous year. 15% thought they were registered with an NHS dentist, but were
      not. Only 28% of all respondents were confirmed registered with an NHS dentist.
      27% said they received private care, and one-third of these said it was because
      they had been unable to find an NHS dentist. In total, 74% of the population
      under study thought they were receiving regular dental care and only 6% did not
      want regular care. More than one-third of respondents volunteered comments about
      dental services. The majority were supportive of dentists but critical of the
      lack of NHS provision. CONCLUSIONS: This survey indicates a substantial unmet
      perceived need in Aylesbury Vale, with more than one-third of this population
      unable to access continuing NHS dental services which they prefer. There is also
      a need for emergency and occasional dental treatment for a small proportion of
      this population. It is likely that a similar situation exists elsewhere in
      England.

PMID- 9599889
TI  - Levels of restorative care under capitation.
AB  - OBJECTIVES: 1. To compare the prevalences of fissure sealants in similar groups
      of 14-15-year-old, regularly-attending patients treated under fee-for-service in
      1989 and capitation in 1994. 2. To calculate the effect of including sealants in
      the restorative index on estimates of interventional treatment carried out on 14
      15-year-old regularly attending patients treated by general dental practitioners
      in 1994. DESIGN: A randomised epidemiological study. SETTING: Secondary schools
      in the Wycombe, Doncaster and Hereford/Worcester areas. METHOD: Random samples of
      14-15-year-old, regularly attending patients treated by dentists practising under
      capitation in three contrasting areas of England were examined in 1994 for the
      presence of decayed, missing and filled teeth and fissure sealants. Restorative
      indices were calculated with and without the inclusion of sealants. The latter
      were compared with restorative indices calculated without the inclusion of
      sealants on regularly attending patients of the same age group when the dentists
      in the same three areas were working under fee-for-service in 1989. RESULTS: The
      prevalence of fissure sealants increased between 1989 and 1994 from 16% to 30% in
      Wycombe, from 13% to 50% in Doncaster and from 25% to 47% in Hereford/Worcester.
      Without fissure sealants the restorative indices fell between 1989 and 1994 from
      a range of 76.5-94.4 to 63.3-87.1. When sealants were included in the restorative
      indices for 1994, they ranged from 79.5-92.9. CONCLUSIONS: There were increases
      in the prevalences of fissure sealants between 1989-1994. When these sealants
      were included in the calculation of restorative indices for 1994, the level of
      restorative care provided by general dental practitioners remained relatively
      high since the introduction of capitation. Although there has been some increase
      in the level of untreated disease, if the restorative index is calculated without
      the inclusion of sealants then there is a risk of underestimating the treatment
      provided by general dental practitioners to control the carious process. Dentists
      appear to be redirecting their efforts into newer treatment/preventive items.

PMID- 9599891
TI  - Topical bupivacaine for pain control following simple dental extractions.
AB  - OBJECTIVE: This study was carried out to examine the effectiveness of topically
      applied bupivacaine 0.25% with adrenaline 1:200,000, for post-operative analgesia
      in children undergoing dental extractions under general anaesthesia. DESIGN:
      Randomised double blind study in a single centre. SETTING: An outpatient dental
      clinic in a district general hospital, in England, in 1997. SUBJECTS AND METHODS:
      Subjects were selected from children of age 7-15 years having six or less
      extractions, and randomised using the closed envelope technique. INTERVENTIONS:
      The local anaesthetic used was bupivacaine 0.25% with adrenaline 1:200,000. MAIN
      OUTCOME MEASURES: Children were asked on waking from the anaesthetic whether they
      had pain or not. Pain was reassessed five and ten minutes post application of
      swabs to determine any changes in pain. RESULTS: Forty-eight children were
      recruited, of these 18 had no pain post-operatively and 6 were withdrawn due to a
      lack of cooperation. Twelve children were randomised to each group. There were 6
      boys and 6 girls in the bupivacaine group (age 7-15 years), and 4 boys and 8
      girls in the saline group. Bupivacaine 0.25% with adrenaline soaked swabs
      resulted in a significant reduction in pain in 10 children at 10 minutes (P =
      0.01). CONCLUSION: Bupivacaine 0.25% with adrenaline 1:200,000, on application to
      exposed sockets is a simple technique that may provide useful post-operative
      analgesia.

PMID- 9599892
TI  - Infection of Capillaria philippinensis in man.

PMID- 9599893
TI  - Glutamine supplementation for low-birth-weight and very low-birth-weight infants.
AB  - Glutamine is a conditionally essential amino acid for low-birth-weight (LBW) and
      very low-birth-weight (VLBW) infants by virtue of its ability to serve as a
      primary respiratory fuel for proliferating cells, a carrier of nitrogen between
      tissues, maintain acid-base balance, promote the growth and integrity of the
      gastrointestinal tract and promote immunologic responses. While adults can
      synthesize glutamine in the muscles and brain to meet essential requirements
      under normal state of health, the LBW and VLBW infants may not be able to do so
      since the enzymes (glutamine synthetase and glutaminase) activities are low. In
      addition, these infants are under stress due to conditions like the respiratory
      distress syndrome, acid-base imbalances, infections, and inadequate immunologic
      responses. Current amino acid mixtures and formula preparations are inadequate to
      meet the needs of these infants for this amino acid. Thus supplementation of
      parenteral and enteral nutrition with glutamine would be beneficial.

PMID- 9599894
TI  - Human intestinal capillariasis (Capillaria philippinensis) in Taiwan.
AB  - A human case of intestinal capillariasis was first recognized in the Philippines
      in the mid-1960s. The parasitosis is a life threatening disease and has been
      reported from Thailand, Japan, Taiwan. Korea, Iran, and Egypt. Clinical symptoms
      include diarrhea, abdominal pain, borborygmi, marked weight loss, protein and
      electrolyte loss, and cachexia. Capillariasis may be fatal if treatment is not
      given early. We observed 7 cases living in the more rural areas of Taiwan. Two
      cases had histories of travelling to Thailand. These two cases might have been
      infected in Thailand while stayed there. The other 5 cases didn't have histories
      of going abroad. According to the route of transmission, freshwater and brackish
      water fish may act as the intermediate host of the parasite. People who like to
      eat raw fish, and have had long term diarrhea with abdominal pain and borborygmi,
      capillariasis philippinensis should be highly suspected. The most simple and
      convenient method of diagnosing capillariasis is stool examination. Treatment
      with mebendazole or albendazole for 20-30 days is known to be effective. All 7
      cases we observed were cured through adequate treatment with anthelmintics and
      general management. A case, found in Kaohsiung Medical College Hospital in 1983,
      may be the first case in Taiwan.

PMID- 9599895
TI  - Urinary endothelin-1 in children with glomerulonephritis.
AB  - Urinary endothelin-1 (ET-1) excretion was studied in 28 children with
      glomerulonephritis. Urinary ET-1 excretion was expressed as a ratio of urinary ET
      1 to urinary creatinine (ET-1/Cr). There was a positive correlation between
      urinary ET-1/Cr and daily total urinary ET-1 in patients (r = 0.65, n = 32, p <
      0.001). Urinary ET-1/Cr in children with glomerulonephritis and normal renal
      function was not different from that of normal controls. Urinary ET-1/Cr in
      glomerulonephritis children with ARF was lowest. These results showed that the
      pattern of urinary ET-1/Cr varied depending on the state of renal function in
      children with glomerulonephritis.

PMID- 9599896
TI  - A follow-up study of annular pancreas in infants and children.
AB  - Fifteen pediatric patients undergoing surgery for annular pancreas from 1984 to
      1996 were analyzed. Vomiting was the most common presenting symptom. Twelve
      patients (80%) had associated anomalies including malrotation (40%), intrinsic
      duodenal obstruction (33%), Down syndrome (27%) and duodenal bands (27%). Their
      ages at operation were between 5 hours and 8.5 years, with a median of 4 days.
      Surgical treatment included duodenojejunostomy in nine, duodenoduodenostomy in
      five and duodenotomy with duodenoplasty in one. The mean duration for
      reestablishment of bowel transit was 17.9 days, with 22.8 days for
      duodenojejunostomy and 12.3 days for duodenoduodenostomy. All cases received
      postoperative follow-up, but only 11 of them were long-term followed until April
      1997, with a duration ranging from 1 year and 2 months to 11 years, with a median
      of 7 years and 5 months. The survival was 100%, but 12 cases (80%) developed
      postoperative complications including cholestatic jaundice (53%), upper
      gastrointestinal motility disorder (47%), failure to thrive (40%) and chronic
      diarrhea (33%). Annular pancreas divisum was noted in one case with chronic
      relapsing pancreatitis. At the end of follow-up (April 1997), when final ages
      ranged from 1 year and 2 months to 18 years and 9 months with a median of 7 years
      and 5 months, there were still problems: steatorrhea in 1, diarrhea after fatty
      diet in 3, malnutrition in 4, failure to thrive in 3 and lower concentration of
      stool trypsin in 3 cases. In conclusion, close long-term follow-up is essential
      for infants treated for annular pancreas because many of them can be expected to
      develop complications, even if the initial postoperative period is uncomplicated
      and survival is excellent.

PMID- 9599897
TI  - Clinical and laboratory correlation of acute Henoch-Schonlein purpura in
      children.
AB  - The clinical and laboratory features of 72 children with Henoch-Schonlein purpura
      (HSP) were examined to determine if there were associations between the
      laboratory indices--including white blood cell (WBC) counts, serum C-reactive
      protein (CRP) levels, platelet (PLT) counts--and the clinical manifestations of
      acute HSP. Marked leukocytosis (WBC > 15,000/mm3), elevation of serum CRP levels
      (> 10 mg/L) and thrombocytosis (PLT > 400 x 10(3)/mm3) were associated with
      gastrointestinal (GI) bleeding, but not associated with abdominal pain in the
      absence of GI bleeding. None of the three parameters was associated with
      arthritis and nephritis. Elevated serum CRP levels alone was associated with
      prolonged hospital course, and may serve as an indicator of disease severity in
      patients with HSP. GI bleeding did not occur in patients with normal WBC counts,
      serum CRP levels, PLT counts (0/19), but occurred in 21.7% (5/23), 50% (8/16),
      and 85.7% (12/14) in patients with only one, two of the three and all three
      laboratory abnormalities, respectively. Patients with GI bleeding had higher mean
      WBC, PLT counts and serum CRP levels than those with abdominal pain in the
      absence of GI bleeding, and than those without abdominal pain. Routine
      measurement of these parameters is warranted to monitor children with acute HSP.

PMID- 9599898
TI  - Whey and casein specific IgE and the cow's milk challenge test for atopic
      children.
AB  - We studied 30 atopic children who suspected of milk allergy by past history (age
      ranging from 1 yr 4 mo to 9 yr 6 mo, mean age: 5.03 yr.) diagnosed as having
      asthma, atopic dermatitis and/or allergic rhinitis. These 30 atopic children had
      been screened from the patients at our outpatient clinic by the Pharmacia CAP
      system RAST FEIA. All of them showed the presence of at least Class II (greater
      than 0.7 ku/l) IgE specific to proteins in cow's milk. Further analysis found IgE
      specific to alpha-lactoalbumin (alpha-LA) elevated in 1 patient (3.3%), 1 patient
      (3.3%) to beta-lactoglobulin (beta-LG), 4 patients (13.3%) to alpha-LA and beta
      LG, 5 patients (16.7%) to casein, 8 patients (26.7%) to casein and alpha-LA, 11
      patients (36.7%) to casein, alpha-LA and beta-LG. After 3 weeks' cow-milk-free
      diet, the patient's milk challenge test was performed at our outpatient clinic.
      According to the test result, none of these 30 atopic children showed clinical
      evidence of significant allergic reaction to cow's milk in the skin, the
      gastrointestinal tract or the respiratory tract either within two hours after the
      challenge test or within 3 days after they went home. We therefore conclude that:
      (1) No single major allergen is apparent in cow's milk: casein, alpha-LA and beta
      LG all show a high proportion of positive reaction. (2) Many atopic children
      fully tolerate cow's milk, although they have high titer of IgE antibodies
      specific to cow's milk. The RAST test is only the first step to screen patients
      with suspected IgE-mediated allergies. To make sure, any positive reaction must
      be confirmed by the "golden standard" for diagnosis, i.e., the double-blind
      placebo-controlled food challenge.

PMID- 9599900
TI  - Lack of association between obesity and dental caries in three-year-old children.
AB  - To investigate whether the obese children are prone to develop dental caries, the
      cross-sectional data from a Three-year-old Children's Health Survey were
      evaluated. The body weight, height, body mass index (BMI), and decayed and filled
      teeth (dft) score were analyzed in 5,133 children. The prevalence of dental
      caries was not different significantly among different BMI groups. There were no
      significant differences in the dft score of carious children among different BMI
      groups. Little or no relationship was found between BMI and dft score. We
      conclude that there is no relationship between carious deciduous teeth and weight
      status in three-year-old children.

PMID- 9599899
TI  - Clinical experience in airway endoscopy in children: an emphasis on the
      comparison between flexible and rigid endoscopy.
AB  - Congenital and acquired lesions of the pediatric airway frequently pose
      perplexing problems in children, infants and newborns. Prompt investigation into
      the etiology and early intervention are essential to decrease the morbidity and
      to prevent some tragic events. Endoscopy grants access to the lesion sites for
      either diagnostic or therapeutic purposes. From April 1994 to May 1997, totally
      509 endoscopic procedures, including 292 flexible and 217 rigid endoscopic
      procedures were performed in 296 pediatric patients at National Taiwan University
      Hospital. For routine diagnostic procedures, the flexible fiberscope is the
      instrument of choice which should include a detailed examination of entire upper
      airway, as farther to tracheobronchi as possible. When flexible endoscopy fails
      to demonstrate the exact airway lesion or certain surgical manipulation is
      demanded, rigid endoscopy is favored. The indications for endoscopy were:
      stridor, respiratory distress, follow-up endoscopy or tracheostoma evaluation,
      feeding difficulty, hoarseness or weak voice, and suspicious airway foreign body.
      Common airway problems in serial orders were: laryngomalacia, subglottic
      stenosis, tracheo/bronchomalacia and airway foreign body. Nearly 20% of patients
      in this series had multiple synchronous airway lesions. There was no major
      complication in our 292 flexible endoscopic procedures. Two major complications
      attributed to endoscopic manipulations occurred in 217 rigid endoscopic
      procedures.

PMID- 9599901
TI  - Hereditary spastic paraplegia: report of two siblings.
AB  - Hereditary spastic paraplegia (HSP) is a degenerative disorder of the central
      nervous system, characterized by progressive weakness and spasticity of the lower
      extremities. The first symptom is usually leg stiffness, unstable gait with
      difficulty in walking. According to the clinical features, hereditary spastic
      paraplegia can be divided into pure type and complicated type. The mode of
      hereditary spastic paraplegia can be autosomal dominant, autosomal recessive or X
      linked. There have been many loci on chromosomes identified in recent years. We
      present two Chinese siblings with unstable gait, a 5-year-3-month-old brother and
      his 3-year-1-month-old sister, who belong to the pure type hereditary spastic
      paraplegia. Both of them had motor deficit on follow up.

PMID- 9599902
TI  - Fetal alcohol syndrome with Arnold-Chiari malformation: report of one case.
AB  - We report a rare case of fetal alcohol syndrome (FAS) with Arnold-Chiari
      malformation. The new-born had the typical facial abnormalities associated with
      FAS and the mother had a history of heavy drinking. CNS malformation, which is
      rarely seen in FAS, was also presented. The relationship between the
      developmental defects and maternal alcohol drinking are discussed together with a
      review of the literature.

PMID- 9599903
TI  - Vacuum extraction delivery complicated with acute subdural hematoma and cerebral
      infarction: report of one case.
AB  - We present a term, 2950 gm female neonate who was delivered by vacuum extraction
      and subsequently developed convulsions 23 hours after birth. Acute
      subduralhematoma was rapidly diagnosed by computed tomographic brain scan and
      successfully removed. The patient had a smooth postoperative recovery but
      cerebral infarction was found during follow up imaging studies. Magnetic
      resonance angiography revealed poor visualization of bilateral posterior cerebral
      arteries. After a follow-up period of 4 months, the infant had normal
      neurological development except for mild microcephalus. We report the occurrence
      of cerebral infarction in an infant following evacuation of a subdural hematoma.
      Onset of the late complication suggests the importance of serial
      neuroradiological and clinical evaluations.

PMID- 9599904
TI  - Pancarditis in an extreme premature newborn following central venous
      catheterisation: report of one case.
AB  - We report a rare complication of pancarditis in an extreme premature neonate with
      a peripheral inserted central venous catheter which was positioned in the right
      atrium. She showed a picture of sepsis, pulmonary embolism, and heart failure.
      This case emphasizes the need for careful monitoring of the neonate with a
      central venous catheter to eliminate possible sequel. Echocardiography may help
      in making an early diagnosis of endocarditis in neonates.

PMID- 9599905
TI  - Antimicrobial resistance: an ecological approach to a growing threat.

PMID- 9599906
TI  - Asymptomatic hypercalcemia in a 51-year-old woman.

PMID- 9599907
TI  - Group A streptococcal necrotizing fasciitis. Diagnosing and treating the "flesh
      eating bacteria syndrome".
AB  - Over the past decade the incidence of necrotizing fasciitis due to group A
      streptococci has increased. Appropriate management of this life-threatening
      infection requires rapid recognition, immediate antibiotic therapy, and
      expeditious surgical debridement or excision.

PMID- 9599908
TI  - Diagnosing and treating depression in primary care patients: looking beyond
      physical complaints.
AB  - Depression is common, but often overlooked because patients with depression often
      present with somatic complaints rather than psychological ones. Primary care
      physicians must learn to recognize depression and be thoroughly familiar with its
      treatment, because this disease is common and serious.

PMID- 9599909
TI  - The connection between chronic fatigue syndrome and neurally mediated
      hypotension.
AB  - Research from several groups of investigators indicates that some patients with
      chronic fatigue syndrome have abnormal vasovagal or vasodepressor responses to
      upright posture. If confirmed, these findings may explain some of the symptoms of
      chronic fatigue syndrome. There is also speculation that neurally mediated
      hypotension may be present in fibromyalgia. This article discusses the original
      research in this area, the results of follow-up studies, and the current approach
      to treating patients with chronic fatigue syndrome in whom neurally mediated
      hypotension is suspected.

PMID- 9599910
TI  - The EPILOG trial. Abciximab prevents ischemic complications during angioplasty.
      Evaluation in PTCA to improve Long-Term Outcome with Abciximab GP IIb/IIIa
      Blockade.

PMID- 9599911
TI  - Radiographic findings in Paget's disease of bone.

PMID- 9599912
TI  - Cancer information and the Internet: benefits and risks.

PMID- 9599913
TI  - Anorectic drugs and valvular heart disease.

PMID- 9599914
TI  - Anorectic drugs and valvular heart disease.

PMID- 9599915
TI  - Clusters of meningococcal disease illustrate differences in management of group B
      and C disease.

PMID- 9599916
TI  - Legionnaires' disease in long distance lorry drivers.

PMID- 9599917
TI  - An outbreak of influenza in four nursing homes in Sheffield.

PMID- 9599918
TI  - Cholera in British tourists returning from Kenya.

PMID- 9599919
TI  - Structure of mammalian orthoreovirus particles.

PMID- 9599920
TI  - Enzymatic and control functions of reovirus structural proteins.

PMID- 9599921
TI  - Assembly of the reovirus genome.

PMID- 9599922
TI  - Temperature-sensitive mutants of reovirus.

PMID- 9599923
TI  - Suppression and reversion of mutant phenotype in reovirus.

PMID- 9599924
TI  - Reovirus cell attachment protein sigma 1: structure-function relationships and
      biogenesis.

PMID- 9599925
TI  - Signal transduction and antiproliferative function of the mammalian receptor for
      type 3 reovirus.

PMID- 9599927
TI  - Reovirus sigma 3 protein: dsRNA binding and inhibition of RNA-activated protein
      kinase.

PMID- 9599926
TI  - Reovirus capsid proteins sigma 3 and mu 1: interactions that influence viral
      entry, assembly, and translational control.

PMID- 9599928
TI  - Reovirus M1 gene expression.

PMID- 9599929
TI  - Molecular mechanisms of persistent infection by reovirus.

PMID- 9599931
TI  - Pathogenesis of reovirus myocarditis.

PMID- 9599930
TI  - Apoptosis and the cytopathic effects of reovirus.

PMID- 9599932
TI  - Pathogenesis of reovirus gastrointestinal and hepatobiliary disease.

PMID- 9599933
TI  - Reovirus and endocrine cells.

PMID- 9599934
TI  - Pathogenesis of reovirus infections of the central nervous system.

PMID- 9599935
TI  - Reoviruses and the interferon system.
AB  - Reovirus induces IFN, and reovirus is sensitive to the antiviral actions of IFN.
      The characteristics of the IFN-inducing capacity of reovirus, and the antiviral
      actions of IFN exerted against reovirus, are dependent upon the specific
      combination of reovirus strain, host cell line, and IFN type. Responses, both IFN
      induction and IFN action, differ quantitatively if not qualitatively and are
      dependent upon the virus, cell, and IFN combination. Stable natural dsRNA,
      identified as the form of nucleic acid that constitutes the reovirus genome, is
      centrally involved in the function of at least three IFN-induced enzymes. Protein
      phosphorylation by PKR, RNA editing by the ADAR adenosine deaminase, and RNA
      degradation by the 2',5'-oligoA pathway all involve dsRNA either as an effector
      or as a substrate. Considerable evidence implicates PKR as a particularly
      important contributor to the IFN-induced antiviral state displayed at the level
      of the single virus-infected cell, where the translation of viral mRNA is often
      observed to be inhibited following treatment with IFN-alpha/beta. In the whole
      animal infected with reovirus, elevated cellular immune responses mediated by
      enhanced expression of MHC class I and class II antigens induced by IFN
      alpha/beta or IFN-gamma may contribute significantly to the overall antiviral
      response.

PMID- 9599936
TI  - Cellular and humoral immunity to reovirus infection.

PMID- 9599937
TI  - Mucosal immunity to reovirus infection.

PMID- 9599938
TI  - Protein and hypervariable tandem repeat diversity in eight African-derived South
      American populations: inferred relationships do not coincide.
AB  - We compared data from individuals living in 4 African Venezuelan and 4 African
      Brazilian communities for 11 protein loci (551 subjects) and 8 hypervariable
      tandem repeat polymorphisms (252 subjects). There is heterogeneity in diversity
      within and between the two sets of loci. On the other hand, African-derived
      Brazilians and Venezuelans do not present marked variability differences between
      themselves. Although the hypervariable loci show gene diversities that are about
      four times higher than those obtained from the protein data, they are not more
      discriminative at the interpopulation level (averages 6% and 4%, respectively).
      Interpopulation differences do not strictly parallel the geographic distances
      between the groups, and population relationships obtained from the protein data
      are not the same as those indicated by hypervariable tandem repeat polymorphisms.
      Caution is needed in establishing relationships considering just one level of the
      biological hierarchy.

PMID- 9599939
TI  - Climate-dependent genetic variation of alpha-2HS-glycoprotein.
AB  - We studied the possible effects of climatic factors on the world distribution of
      alleles determining alpha 2-HS-glycoprotein (AHSG) phenotypes in human
      populations. New data on AHSG polymorphism in certain ethnic groups of Russia are
      presented. All available data on the distribution of AHSG gene frequencies in the
      world (number of populations n = 51) were used to analyze possible correlations
      between AHSG*2 allele frequencies and seven climatic-geographic parameters. A
      strong positive correlation was found between AHSG*2 allele frequency and
      geographic latitude of territories inhabited by the study populations (r =
      0.814). The dependence of the AHSG*2 allele distribution in the world on the
      intensity of ultraviolet radiation (400-315 nm) was estimated at r = -0.826. Such
      climatic characteristics as the total amount of insolation and the average annual
      temperature proved to make equal contributions to variation in AHSG*2 allele
      frequency (r = -0.683 and -0.658, respectively). A computer cartographic model of
      the AHSG*2 allele distribution in the Old World populations of the Northern
      Hemisphere was constructed.

PMID- 9599940
TI  - Apolipoprotein A kringle 4 polymorphism and serum lipoprotein (a) concentrations
      in African blacks.
AB  - Several epidemiological studies have established that elevated serum lipoprotein
      (a) [Lp(a)] levels are independent risk factors for coronary heart disease,
      stroke, and restenosis of coronary lesions in white and Asian populations. Serum
      Lp(a) levels vary over a 1000-fold range among individuals and are under strict
      genetic control. Serum Lp(a) levels are significantly higher in populations with
      African ancestry than in populations of European ancestry. The APOA gene exhibits
      hypervariable length polymorphism resulting from a variable number of expressed
      kringle 4 repeats. An inverse relationship exists between the size of kringle 4
      repeats and serum Lp(a) levels. However, most studies have been conducted in
      whites, and the data are scanty in African populations. To explore this
      relationship among Africans, we determined serum Lp(a) levels and APOA Kringle 4
      size polymorphisms in 781 unrelated Africans (490 men, 291 women) from Benin
      City, Nigeria. Mean and median serum Lp(a) values were 25.6 +/- 0.6 mg/dl and
      20.9 mg/dl, respectively. Although there was no difference in mean Lp(a) values
      between men and women, median Lp(a) values were higher in women than in men (p =
      0.02). Using SDS-agarose gel electrophoresis, we detected 38 APOA isoforms, the
      highest number recorded to data. There were 10 consecutive medium-size alleles
      whose frequencies ranged between 4.2% and 10.9%, and together they accounted for
      72.8% of the alleles observed in this population. Spearman's correlation
      coefficients showed an inverse relationship between the size of the APOA isoform
      and Lp(a) levels using either single-banded (r = 0.46; p < 0.0001) or double
      banded (r = 0.42; p < 0.0001) phenotypes. Using random effects analysis of
      variance on the entire sample, the APOA size polymorphism explained about 15% of
      the phenotypic variation in Lp(a) levels. These data suggest that despite
      significant correlation between the APOA kringle 4 size polymorphism and Lp(a)
      levels, other sequence variations either in the APOA gene or closely linked genes
      may account for relatively higher Lp(a) levels found in Africans.

PMID- 9599941
TI  - Genetic characterization of APOB and D17S5 AFLP loci in a sample from the Basque
      Country (northern Spain).
AB  - VNTR polymorphism of AFLP loci D17S5 and APOB was analyzed in 100 unrelated
      individuals residing in the Basque Country by PCR amplification and
      polyacrylamide gel electrophoresis. Population parameters were estimated to
      validate these loci as routine markers in human identification. Thus, although
      both loci showed extensive polymorphism (with gene diversities of approximately
      80% for both systems) and although concordance with Hardy-Weinberg equilibrium
      and linkage equilibrium was observed, comparisons with other populations
      displayed significant differences. Moreover, further analysis of neutral
      parameters limits this validation to D17S5 because APOB displays excesses of both
      the total number of alleles and the number of rare alleles; possible reasons for
      this discrepancy (presence of deleterious alleles, bottleneck effect, admixture,
      complexity of APOB polymorphism) are discussed.

PMID- 9599942
TI  - D1S80 polymorphism in Amerindians from the Amazon region of Brazil.
AB  - The allele frequency distribution at the D1S80 locus (pMCT118) was analyzed in
      five Amerindian tribes from the Brazilian Amazon (Zoe, Awa-Guaja, Urubu-Kaapor,
      Katuena, and Xikrin of Bacaja) and was compared with distributions described for
      other worldwide populations. Nine different segregating alleles were identified
      in a sample of 139 individuals; alleles *18, *25, and *30 predominated in all
      tribes. Although the tribes are usually characterized by a low within-population
      diversity, they have a high interpopulational diversity, probably because of
      genetic drift acting on small isolated populations. Our data are similar to data
      for other Brazilian Amerindian tribes; these were combined for comparison with
      other human populations. Brazilian Amerindians are similar to the Pehuenche from
      Chile and to North American natives. However, the closest similarity was observed
      between Brazilian Amerindians and Polynesian populations (Samoans), probably
      reflecting common ancestry. Brazilian Amerindians and Asian populations have some
      similarities in terms of allele distribution (high frequencies of alleles *18 and
      *30), but the values of heterozygosity and the number of alleles are higher in
      Asians. Brazilian Amerindians are also clearly different from Europeans.

PMID- 9599943
TI  - Variability of birth-weight distributions by sex and ethnicity: analysis using
      mixture models.
AB  - Birth weight is the most important proximate determinant of the level of infant
      mortality. However, the association between birth weight and infant mortality is
      not constant among populations. For example, the mortality of African American
      infants is lower at low birth weight but higher at high birth weight compared
      with European American infants. One possible explanation is that birth cohorts
      are heterogeneous even after controlling for birth weight, ethnicity, sex, and
      multiple births. The analyses presented here use Gaussian mixture models to
      explore the interpopulation variation in the shape of the birth-weight
      distribution for evidence of intrapopulation heterogeneity. The results suggest
      that a two-component mixture model provides an excellent description of human
      birth-weight distributions. Further statistical analyses of sex and ethnic
      differences indicate (1) that the birth-weight distributions and heterogeneity
      within the distribution vary between the sexes and among ethnic groups and (2)
      that one specific component is more closely associated with the overall level of
      infant mortality. The results support the hypothesis that birth cohorts can
      consist of two or more subpopulations at differential risk of mortality.
      Differences in the subpopulation composition of birth cohorts (i.e., differences
      in the level of heterogeneity among the various ethnic groups) might partially
      explain the interethnic variation in birth-weight-specific mortality. Further
      development of these mixture models should provide important additional
      information concerning the biological, environmental, and social determinants of
      birth weight and infant mortality.

PMID- 9599944
TI  - Multiple kinship in two Spanish regions: new model relating multiple and simple
      consanguinity.
AB  - The structure of the different categories of multiple consanguineous marriages
      (MCMs) and their historical variation patterns are analyzed in the Spanish
      dioceses of Alava (Basque Country) and Siguenza-Guadalajara (Castile).
      Consanguineous marriages, up to third cousins, were taken from ecclesiastical
      dispensations, and the periods studied were 1831-1980 for Alava and 1861-1980 for
      Siguenza-Guadalajara. Significant differences exist in the MCM rates in the two
      Spanish areas. In this study a model is proposed to prove that in a general
      population there may be dependence between MCM rates for specific relationships
      and the frequencies of those types of relationships in the form of simple
      consanguineous marriages (SCMs). The effects of avoidance and preferentiality and
      of underreporting are discussed to explain the deviations between observed and
      expected consanguineous marriage frequencies. A limit to the weight of remote
      consanguinity on the population inbreeding coefficient F is determined. The
      relationship between FT/FS and ms values from our two Spanish populations are
      fitted to curvilinear regressions. FT is the total population inbreeding
      coefficient, FS is the contribution to FT from SCMs, and ms is the relative
      observed frequency of SCMs in the general population.

PMID- 9599945
TI  - Ethnohistorical evidence for inbreeding among the pre-Hispanic Mixtec royal
      caste.
AB  - Pre-Columbian Mixtec social organization was distinguished by the tight endogamy
      of the ruling class, which included many consanguineous marriages. It was also
      characterized by a vigorous historical and genealogical tradition. The historical
      documents, or codices, provide materials for the calculation of the levels of
      inbreeding present before the Spanish Conquest. A genealogical analysis of
      inbreeding was performed on the combined pedigree, which spanned the tenth
      through sixteenth centuries, of all individuals connected by ancestry, descent,
      or marriage with Lord 8 Deer Jaguar Claw of Tilantongo (A.D. 1063-1115). Sixty of
      the 217 couples (27.65%) were consanguineous. When only couples of wholly known
      grandparentage were considered (N = 39), F = 0.1051. The mean F of all couples,
      even those where one spouse was of unknown parentage, was 0.0243. Over the 550
      years of the pedigree the maximum F in any 52-year period was 0.1324. This level
      of inbreeding is sufficient to produce noticeable effects on population structure
      and affinities over time.

PMID- 9599946
TI  - Dermatoglyphic relationships among South Amerindian populations.
AB  - The biological affinities among 17 South American aboriginal populations are
      examined by means of a multivariate analysis of their dermatoglyphic finger
      patterns. Different analytical methods [cluster analysis, nonmetric
      multidimensional scaling, and multiresponse permutation procedure (based on
      distances derived from principal components analysis)] reveal interpopulation
      relationships consistent with Loukotka's language classification. The paleo
      American tribes from the Gran Chaco and Brazil share a high incidence of whorls
      as a distinctive feature. The Andean and tropical forest groups, which present a
      greater prevalence of arches and ulnar loops, appear to be closely related to
      each other, suggesting a more recent common origin and/or substantial gene flow
      between them.

PMID- 9599947
TI  - Demographic implications of socioeconomic transition among the tribal populations
      of Manipur, India.
AB  - The demographic implications of socioeconomic transition are studied among the
      three subsistence categories of the Gangte, a little known tribe from northeast
      India. Reproductive histories of 444 ever-married women and other data on the 343
      households from which these women were drawn were collected from 11 villages
      representing the 3 transitional groups. A trend of increasing household income
      and literacy of couples was observed from shifting cultivators to settled
      agriculturists to the town-dwelling Gangte. The effect of socioeconomic
      transition is also seen in the constriction at the base of the age-sex pyramid of
      the town dwellers compared with the other subsistence categories, suggesting a
      relatively lower proportion of children in the 0-5-year-old age group. Although
      exogamy is practiced among all the subsistence categories, a considerably higher
      percentage of admixture with non-Gangte is observed among the town dwellers
      compared with the others. Overall infant and child mortality among the Gangte is
      low. However, variation exists among the three subsistence groups in the sense
      that a considerable reduction is seen from the traditional shifting cultivators
      to the urbanized town dwellers, reflecting better socioeconomic conditions and
      greater awareness and accessibility of the town dwellers to public health
      amenities. No consistent or perceptible trend is evident in mean number of live
      births. The genetic implications of this demographic transition are reflected in
      Crow's indexes of selection.

PMID- 9599948
TI  - Variation in the number of FMR1 microsatellite repeats in three subgroups of the
      Hellenic population.
AB  - Microsatellites have been used for human evolution and origin studies by
      comparing their frequency, diversity, and allele size. In this study we report
      the analysis of three microsatellite loci, FMR1 CGG and flanking DXS548 and
      FRAXAC2, in three separate groups of the Hellenic population: Athens,
      representing the general Hellenic population; Epirus (northwest Greece); and
      Cyprus. Significant variations in frequency and diversity were found in the three
      groups. Compared with Athens, Epirus had a tendency for longer alleles and a
      higher heterozygosity for DXS548. Cyprus had a frequency of CGG alleles similar
      to Athens but a low heterozygosity and a limited number of alleles at DXS548 and
      FRAXAC2. Allele differences of microsatellite loci not only are present in remote
      populations but also are evident between groups belonging to the same population.
      Microsatellite analysis could be a useful tool for identifying the origin of the
      founder chromosomes in intra-population studies and the time elapsed from the
      establishment of each population subgroup.

PMID- 9599949
TI  - Preparation & standardization of the goat lung surfactant extract.
AB  - Exogenous goat lung surfactant extract (GLSE) was obtained by chloroform-methanol
      extraction of the centrifuged lung lavage. Four lungs provided around 250 mg of
      surfactant. GLSE has a phospholipid content of 50 percent, cholesterol of 1.5
      percent and protein content under 1 percent. The preparation was
      bacteriologically sterile and had a shelf life of at least one month at 4 degrees
      C. Endotracheal administration of surfactant (50 mg/kg) in a rat lung model
      rendered surfactant deficient by saline lavage, restored the compliance
      characteristics to normal, thus documenting biological activity of the
      preparation. The cost of a course of 2 doses of surfactant replacement therapy
      was estimated to be as low as Rs 500/-. The study opens up the possibility of
      surfactant replacement therapy for the management of neonatal respiratory
      distress syndrome in India by an indigenous product at an affordable cost.

PMID- 9599950
TI  - Effect of chronic ethanol feeding on intestinal alkaline phosphatase activity in
      rats.
AB  - The effect of chronic ethanol feeding has been studied on intestinal alkaline
      phosphatase (IAP) activity. The enzyme was assayed using p-nitrophenyl phosphate
      (PNPP), phenylphosphate (PhP) and beta-glycerophosphate (beta GP) as the
      substrates. Feeding of ethanol for 10 days did not effect the enzyme activity but
      it was markedly elevated in animals fed ethanol for 20 or 30 days. However,
      ethanol administration to rats, for over 6 wk exhibited a decline in IAP
      activity, both in the soluble and membrane fractions of intestine. Kinetic
      studies revealed an enhancement in Vmax with no change in apparent Km after 30
      days of ethanol feeding and a decrease in Vmax after 6 wk of ethanol ingestion.
      These results were confirmed by assaying the enzyme activity in non-denatured
      polyacrylamide gels using 5-bromo-4-chloro-3-indoly1 phosphate (BCIP) as the
      substrate. These findings suggest differential changes in IAP activity in
      response to ethanol feeding in rats.

PMID- 9599951
TI  - Interplay of matrices in cartilage synovial fluid combine under moderate & high
      loadings.
AB  - Interplay of the constituents of the articular cartilage synovial fluid combine
      and its role was examined through the biochemical and rheological studies on
      bovine joints. The results showed an inverse relationship between the changes in
      the hyaluronic acid of synovial fluid and the proteoglycans content in articular
      cartilage together with alterations in the rheological properties of synovial
      fluid. The study indicated that the inter-movement of fluid solutes across the
      cartilage and synovial fluid may have an important role in the pathophysiology of
      osteoarthritis.

PMID- 9599952
TI  - Haemorheological behaviour of erythrocytes & risk factor profile in patients
      suffering from Waldenstrom's macroglobulinaemia.
AB  - The plasma viscosity, haematocrit, and erythrocyte aggregation and deformability
      of blood samples of patients of Waldenstrom's macroglobulinaemia were measured by
      capillary viscometer, microcentrifuge, Myrenne aggregometer and filtrometer
      respectively and correlated with the serum IgM concentrations. The observed
      increase in plasma viscosity and erythrocyte aggregation and decrease in their
      deformability were attributed to the increase in the concentration of IgM.
      Haematocrit was also decreased compared to normal subjects. Based on these
      parameters a haemorheological risk factor profile was developed and an overall
      risk factor calculated. An increase in the risk factor in these patients was
      observed. The haemorheological profile and the calculated risk factors not only
      help in establishing the inter-relationship of these parameters in the disease
      state but also to evaluate the severity of the disease.

PMID- 9599953
TI  - Beta-thalassaemia mutations in northern India (Delhi).
AB  - The present study was undertaken to define beta-thalassaemia mutations prevalent
      in northern India (Delhi). Forty six children of beta-thalassaemia major and
      their families were investigated. DNA was extracted from leucocytes and screened
      for mutations prevalent in the Indian population. These mutations included 619bp
      deletion, IVS 1-1 (G-T), IVS 1-5 (G-C), frameshift mutations FS 8/9 (+G), FS
      41/42 (-CTTT), Codon 16(-C), Codon 15 (G-A), codon 30 (G-C), IVS 1-110 (G-A) and 
      88 (C-T). 619 bp deletion mutation was detected directly by amplification of DNA
      by PCR followed by agarose gel electrophoresis. Other mutations were studied by
      DNA amplification and dot blot hybridization using synthetic normal and mutant
      oligonucleotide probes labelled at 5' end with gamma-32 P-ATP. Five mutations
      accounted for all the chromosomes in 46 patients. 619 bp deletion mutation was
      found to be the commonest mutation (34.8%) followed by IVS 1-5 (G-C) in 22.8 per
      cent, IVS 1-1 (G-T) in 19.6 per cent, FS 8/9 (+G) in 13 per cent and FS 41/42 (
      CTTT) in 9.8 per cent. Nineteen (41.3%) patients were homozygous and 27 (58.7%)
      double heterozygous for different beta-thalassaemia mutations. This observation
      of limited number of mutations is significant and will be useful in planning
      strategies for prenatal diagnosis of beta-thalassaemia in northern India.

PMID- 9599954
TI  - An experimental study on evaluation of chemical antagonists induced snake venom
      neutralization.
AB  - The present investigation explored the snake venom neutralizing capacity of four
      chemical compounds (2-hydroxy-4-methoxy benzoic acid, anisic acid, salicylic acid
      and aspirin) in experimental animals. The venoms of common Indian snakes Viper
      russellii, Echis carinatus, Naja kaouthia and Ophiophagus hannah were taken to
      evaluate the lethal, haemorrhagic and defibrinogenation action neutralization.
      Lethal action of venom was maximum neutralized with 2-hydroxy-4-methoxy benzoic
      acid and anisic acid, both in in vitro and in vivo studies. Haemorrhagic activity
      of venom (Viper and Echis) was maximum neutralized with salicylic acid. Viper
      venom induced defibrination was maximally neutralized with 2-hydroxy-4-methoxy
      benzoic acid and anisic acid in vitro studies. The exact mechanisms of venom
      neutralization by the chemical compounds were not established, except for 2
      hydroxy-4-methoxy benzoic acid, where the functional groups, methoxy and hydroxy
      were partly responsible for the neutralization of the lethal effect and
      haemorrhagic activity.

PMID- 9599955
TI  - What follow-up studies say about postschool life for young men and women with
      learning disabilities: a critical look at the literature.
AB  - Follow-up studies examining the outcomes for children and youth with learning
      disabilities who attended special education have appeared in the literature for
      decades. As American society becomes more technologically advanced and
      competitive, postsecondary school opportunities and subsequent employment choices
      that are meaningful and provide a livable wage teeter out of the reach of young
      people with learning disabilities. Follow-up study investigators seek to
      understand how to better prepare youth to meet these challenges by studying their
      long-term outcomes. The authors review data from 13 frequently referenced follow
      up studies regarding postschool outcomes, postsecondary education, and
      employment, with attention to gender differences, for youth with learning
      disabilities who were served by and graduated from special education programs
      nationwide. They take a critical look at contradictions in the findings and
      discuss five methodological issues that seem to influence the conduct and
      interpretation of follow-up studies: aggregating data across disability
      categories; combining data on graduates who have been out of school for unequal
      periods of time; ignoring the issues of missing data, participant attrition, and
      incomplete data sets; combining data from different informants; and using
      nonequivalent databases to make comparisons to a population with no disabilities.
      The authors provide recommendations for conducting follow-up research on the long
      term quality of life of children and youth with disabilities and their families.

PMID- 9599956
TI  - The national learning disabilities postsecondary data bank: an overview.
AB  - A survey was developed to assess support services, procedures, policies, the
      proportion of students with learning disabilities (LD), and the factors that
      affect differences in proportion in a nationally representative sample of
      postsecondary institutions (PSIs). The factors investigated included general
      characteristics about the PSI, such as size of the student body and type of PSI.
      The specific characteristics investigated in regard to LD were admissions
      procedures, year of initiation of LD support services, type and location of
      support services, eligibility criteria for services and accommodations, the
      number of students with LD, and demographic and diagnostic information available.
      In this article, descriptive data regarding the services, practices, policies,
      procedures, and proportions are provided. The findings indicated that the
      proportion of students with LD ranged from .5% to almost 10%. The factors that
      had a significant impact on the proportion of students with LD were size of the
      student body, the type of institution, the institution's Carnegie classification,
      and whether the institution offered graduate degree programs. These findings and
      their implications are discussed.

PMID- 9599958
TI  - Job satisfaction of college graduates with learning disabilities.
AB  - Job satisfaction, as assessed via five scales that posed questions concerning
      colleagues, work, supervision, pay, and promotion, as well as overall total job
      satisfaction, was examined for 55 self-identified college graduates with learning
      disabilities (LD) and 55 control graduates matched by gender, major, degree, and
      graduation year. All participants graduated from a competitive midwestern
      university from 1987 to 1994 and represented advantaged groups when compared to
      both LD and non-LD populations. The graduates with LD required significantly more
      time to complete their degrees and showed significantly lower CPAs. Data analysis
      indicated that the graduates with LD perceived themselves as receiving
      significantly less pay and promotion opportunities, and reported less total job
      satisfaction, than graduates without LD. However, no significant salary
      differences between the groups were found. The implications of these findings are
      examined.

PMID- 9599957
TI  - Foreign language learning difficulties: an historical perspective.
AB  - For 10 years, the authors of this article have examined cognitive, affective, and
      linguistic influences on foreign language learning. They have proposed the
      Linguistic Coding Differences Hypothesis (LCDH) as a model for understanding
      foreign language learning problems. The authors review their empirical support
      for the LCDH and explain the diagnostic, pedagogical, and policy implications of
      their research.

PMID- 9599959
TI  - Longitudinal research in learning disabilities: report on an international
      symposium.
AB  - In June of 1995 an international symposium on longitudinal research in learning
      disabilities (LD) was held in Missillac, France. The purpose of the symposium was
      to bring together an international panel of experts in this area to promote
      international dialogue on longitudinal research in LD, define and develop
      guidelines for conducting such research, identify problems inherent in this type
      of research and methods to alleviate them, and establish research priorities.
      This article synthesizes and highlights the information that emerged from
      individual presentations and ensuing discussions. Generic considerations
      regarding longitudinal research are presented; however, particular emphasis is
      given to the confluence of longitudinal research and learning disabilities.

PMID- 9599960
TI  - Psychological behaviorism's reading therapy program: parents as reading
      therapists for their children's reading disability.
AB  - The study presents data on the effectiveness of a parent-administered behavioral
      reading therapy program. Ten parents administered the therapy program to their
      second- to fourth-grade children with reading disability. All 10 children
      received 70 therapy sessions (30 minutes per session), with 5 of the 10 children
      receiving approximately 51 additional sessions, for a total of 121 sessions.
      Parents were able to administer the program effectively, and the children
      participated in an enthusiastic manner. Detailed records from the therapy
      sessions showed a high degree of mastery of the reading materials, and the
      children also showed significant and clinically meaningful improvements on
      standardized reading measures. Although the results must be viewed cautiously
      given the absence of a control group, the potential of the parent-administered
      reading therapy program for the remediation of reading disability seems good.

PMID- 9599961
TI  - Interpretation of facial expressions of affect in children with learning
      disabilities with verbal or nonverbal deficits.
AB  - The ability to identify facial expressions of happiness, sadness, anger,
      surprise,fear, and disgust was studied in 48 nondisabled children and 76 children
      with learning disabilities aged 9 through 12. On the basis of their performance
      on the Rey Auditory-Verbal Learning Test and the Benton Visual Retention Test,
      the LD group was divided into three subgroups: those with verbal deficits (VD),
      nonverbal deficits (NVD), and both verbal and nonverbal (BD) deficits. The
      measure of ability to interpret facial expressions of affect was a shortened
      version of Ekman and Friesen's Pictures of Facial Affect. Overall, the
      nondisabled group had better interpretive ability than the three learning
      disabled groups and the VD group had better ability than the NVD and BD groups.
      Although the identification level of the nondisabled group differed from that of
      the VD group only for surprise, it was superior to that of the NVD and BD groups
      for four of the six emotions. Happiness was the easiest to identify, and the
      remaining emotions in ascending order of difficulty were anger, surprise,
      sadness, fear, and disgust. Older subjects did better than younger ones only for
      fear and disgust, and boys and girls did not differ in interpretive ability.
      These findings are discussed in terms of the need to take note of the
      heterogeneity of the learning disabled population and the particular
      vulnerability to social imperception of children with nonverbal deficits.

PMID- 9599962
TI  - Learning disability, attention-deficit disorder, and language impairment as
      outcomes of prematurity: a longitudinal descriptive study.
AB  - A longitudinal study of mildly preterm children and full-term comparison children
      found a higher-than-expected percentage among preterm children of learning
      disabilities, attention-deficit disorder (ADD), language impairment, mild
      neurologic impairment, and general school concerns by Grade 5. Seventy-five
      percent of the preterms fell into the above outcome diagnostic categories.
      Examination of early developmental patterns reflected differences in attention
      deployment at ages 13 months and 15 months, manifesting as increased engaged time
      on the part of the children with ADD, with a greater number of attentional
      shifts, and as decreased engaged time for the other outcome diagnostic
      categories. At 20, 24, and 30 months, mothers' perceptions of their children's
      competence revealed generally strong assessment of competence among children
      later identified as ADD, and weak competence in the other outcome diagnostic
      categories. Variability distinguished the identified groups at all ages and is
      evident in the Stanford-Binet subscale scores at age 3.

PMID- 9599963
TI  - Effects of the failure free reading program on students with severe reading
      disabilities.
AB  - Reading problems are among the most prevalent concerns for those who teach
      students with learning disabilities. In the present research, 39 students with
      severe reading problems were taught word recognition and comprehension skills
      using the failure free Reading Program. The intervention is based on principles
      identified in research on successful reading programs. Key steps in the program
      included (a) previewing the story, (b) listening to the story being read, (c)
      presenting content from the story, (d) reading the story, and (e) reviewing the
      story. Improved performance in letter-word identification, word attack,
      comprehension, and dictation was evident after intensive intervention.
      Discrepancies between intellectual ability and reading achievement decreased in
      more than half of the students. The failure free Reading Program seems to hold
      promise for improving reading in students with learning disabilities.

PMID- 9599964
TI  - Alcohol and insulin sensitivity.
AB  - Compared to heavy drinking and abstinence, a moderate consumption of alcohol is
      associated with lower mortality rates due to coronary heart disease. About half
      of the protective effect of alcohol on cardiovascular risk can be explained by
      its ability to raise HDL-cholesterol. Alcohol can influence HDL metabolism at
      more than one site. Since light-to-moderate alcohol intake is associated with
      enhanced insulin sensitivity and improvement of insulin sensitivity results in
      higher HDL-cholesterol levels, it is suggested that this is one of the routes
      taken by alcohol to act upon HDL metabolism. Whether interrelated or not, both
      the HDL-cholesterol increase and enhanced insulin sensitivity are considered to
      have a beneficial effect on the process of atherosclerosis. Because of the well
      known adverse consequences of excess alcohol use, these facts have not changed
      public health policy. On the other hand, they may have an impact on advice to
      selected patients, diabetics or non-diabetics.

PMID- 9599965
TI  - Strategy in asymptomatic and mildly symptomatic primary hyperparathyroidism, new
      arguments for the surgical option.

PMID- 9599966
TI  - Tuberculosis and pregnancy--a provincial study (1990-1996).
AB  - BACKGROUND: Several studies suggest that physiological changes in pregnancy mimic
      early symptoms of tuberculosis. If true, this could influence the diagnostic
      delay of the disease and the outcome of pregnancy. METHODS: From the register of
      the Public Health Centre, all female patients with culture-proven tuberculosis
      aged between 22 and 35 years in the Province of Zeeland in the period 1990-1996
      have been identified. Data on symptoms, delay, therapy and outcome of the
      pregnancy have been collected. Risk factors for an early diagnosis have been
      identified. RESULTS: In nearly one-third of the patients with tuberculosis (n =
      14), it has been possible to make a presumptive diagnosis on the basis of a chest
      X-ray only. Patients with tuberculosis associated with pregnancy are more likely
      than their non-pregnant counterparts to have non-specific symptoms which are, at
      most, moderate (p = 0.002). Diagnosis has also been hampered by non-cavernous,
      smear-negative presentation of the disease. In addition, women with pulmonary
      tuberculosis associated with pregnancy are more likely to postpone having a chest
      X-ray taken (p = 0.02), which contributes to the delay. CONCLUSION: As the
      clinical features of tuberculosis in pregnancy are moderate, a high index of
      clinical suspicion is necessary. Nevertheless, the favourable outcome suggests
      that (if all risk factors are taken into account) lung tuberculosis in pregnant
      women in The Netherlands can be discovered sufficiently early within the limits
      of the current screening programme to prevent harm to mother or child.

PMID- 9599967
TI  - The allopurinol hypersensitivity syndrome.
AB  - We describe a 61-year-old male patient who was treated with allopurinol and
      developed fever, a skin rash, eosinophilia and severe renal and liver
      dysfunction. We discuss the allopurinol hypersensitivity syndrome as a serious
      complication of the use of allopurinol, and briefly review the aetiology,
      prevention and treatment modalities.

PMID- 9599968
TI  - Preclinical Cushing's syndrome in patients with an adrenal incidentaloma.
AB  - BACKGROUND: Autonomous (hyper-)secretion of cortisol without classical stigmata
      of Cushing's syndrome occurs in 10-15% of patients with incidentally detected
      adrenal tumors (incidentalomas). METHODS: We present the clinical and biochemical
      data of four such patients. Two patients had hypertension and one both
      hypertension and non-insulin-dependent diabetes mellitus, but none showed
      classical stigmata of Cushing's syndrome. RESULTS: All patients showed
      insufficient suppression of plasma cortisol during a 1 mg dexamethasone screening
      test. Plasma ACTH levels were suppressed in all patients. However, in three out
      of four patients the diurnal rhythm of plasma cortisol was intact and these three
      patients also showed a response of plasma cortisol after administration of
      corticotropin-releasing hormone. All patients underwent unilateral adrenalectomy.
      A carcinoma was found in one patient and an adenoma in the remaining three.
      Postoperatively, blood pressure had normalized in 2 out of 3 hypertensive
      patients, whereas non-insulin-dependent diabetes mellitus had disappeared in 1
      patient. Postoperative endocrine evaluation showed no abnormalities anymore.
      CONCLUSIONS: We conclude that dexamethasone testing may reveal autonomous (hyper
      )secretion of cortisol in adrenal incidentalomas. Adrenalectomy should be
      considered, especially when hypertension and/or non-insulin-dependent diabetes
      mellitus are present. One should be alert to the development of adrenal
      insufficiency after unilateral adrenalectomy.

PMID- 9599969
TI  - Rapid onset pulmonary edema (flash edema) in renal artery stenosis.
AB  - Abrupt onset pulmonary edema, that rapidly resolves (flash edema) may be due to
      renal artery stenosis. We describe two patients with renal artery stenosis who
      experienced a life-threatening episode of flash edema. Relief of the stenosis
      prevented recurrence of the flash edema.

PMID- 9599970
TI  - Health implications for Papua New Guinea of chlamydial infections.

PMID- 9599971
TI  - Otitis media with effusion in children: an audiological case series study.
AB  - Otitis media with effusion (OME) was studied in detail in 100 children seen at
      the Ear, Nose and Throat (ENT) Clinic of Port Moresby General Hospital (PMGH)
      between June 1992 and June 1994. More males were examined than females. The
      majority of patients were from the National Capital District and Central
      Province. Pure-tone and impedance audiometry were performed to assess the type,
      amount and pattern of hearing loss. A characteristic audiogram for OME with
      improved air conduction (AC) and decreased bone conduction (BC) hearing at 2 KHz
      and AC loss at both low and high frequencies was established. Bilateral
      myringotomy and grommet insertion was performed in 30 of these children.
      Significant improvement in hearing threshold at all frequencies was found,
      indicating hearing success with surgery. Otitis media with effusion is a disease
      of considerable public health importance and there is a need to increase public
      and professional awareness of it in Papua New Guinea.

PMID- 9599972
TI  - The clinical diagnosis and treatment of important childhood diseases in rural
      Papua New Guinea.
AB  - This study used multiple standardized instruments to evaluate the quality of the
      clinical management of the common childhood diseases in rural Papua New Guinea.
      The findings indicate major inadequacies in the quality of history taking,
      examination, record keeping, diagnosis and treatment of the common causes of
      childhood morbidity and mortality. To improve case management by health workers
      in rural clinical situations everything possible must be done to make good
      clinical management easy and practical. This should involve provision of
      practical reinforcing tools, training and supervision which target rural health
      workers as valuable human resources, and community education which maximizes the
      contribution that community members can make to early diagnosis and good
      management.

PMID- 9599973
TI  - Eye movements and schizophrenia in Papua New Guinea: qualitative analyses with
      case histories.
AB  - Smooth pursuit eye movement dysfunction is a psychophysiological and genetic
      marker for schizophrenia seen in 50-80% of patients and in about 40% of their
      first-degree relatives. In this study, we qualitatively assessed the smooth
      pursuit eye movements of 33 psychiatric patients (including 32 diagnosed with
      schizophrenia) and 30 control subjects in the Port Moresby area of Papua New
      Guinea. Brief case histories of each patient were also reviewed. Using a
      conservative estimate of smooth pursuit dysfunction, we found that 42% of the
      psychiatric patients had the marker, compared to 10% of the controls. Specific
      eye movement abnormalities were also much more common among the patients. A
      patient who had previously 'run amok' and another who was a cargo cultist had
      smooth pursuit dysfunction; a patient whose psychotic symptoms may have been due
      to cerebral malaria did not have the marker. Highland and coastal patients were
      similar in their expression of the marker. This study, the first of its kind done
      outside of large-scale, urbanized societies, provides further evidence for a
      common biological basis for schizophrenia in biologically and culturally diverse
      populations worldwide.

PMID- 9599974
TI  - Gilles de la Tourette syndrome in Papua New Guinea.
AB  - Gilles de la Tourette syndrome is characterized by (a) onset usually in childhood
      and adolescence between 2 and 15 years of age, (b) violent facial tics and
      coprolalia, (c) increased excitability and apathy, (d) progressive increase in
      the intensity of symptoms, and (e) a chronic course. The syndrome is three times
      more common in males than in females. It is no longer considered the rarity it
      used to be, with a reported frequency of 1 to 5 per 10,000 population in western
      countries. This paper is the first report of Gilles de la Tourette syndrome in
      Papua New Guinea. The family history method and the family study method were used
      for this study after the index patient had been identified. The case report is
      presented with a diagram of the pedigree of the extended family of the index
      patient. A total of four cases of Gilles de la Tourette syndrome were reported in
      three generations of the extended family. In conclusion, further clinical and
      genetic research (including twin studies) into Gilles de la Tourette syndrome is
      recommended in Papua New Guinea.

PMID- 9599975
TI  - Primary postpartum haemorrhage: causes, aetiological risk factors, prevention and
      management.

PMID- 9599976
TI  - Bush knife multiple flexor tendon injuries in Western Province.

PMID- 9599977
TI  - Trauma in Papua New Guinea--an epidemic out of control.

PMID- 9599978
TI  - The trauma burden in Port Moresby.

PMID- 9599979
TI  - Head injuries in Papua New Guinea.
AB  - Head injuries are the commonest cause of death in the surgical wards in Port
      Moresby and the commonest cause of death in road accidents. Three prospective and
      retrospective studies performed over the last decade aimed to determine the
      pathology and outcome in 274 head injuries admitted to Goroka in 1988-1991 (4
      years) and Port Moresby in 1984-1985 and 1992-1993 (total 2.5 years). Head
      injuries were managed by general surgeons without CT scanning or intracranial
      pressure monitoring. There were 196 adults and 78 (28%) children; 195 were male
      and 79 female. Assaults (32%), motor vehicle accidents (49%) and falls (17%) were
      the commonest modes of injury. The case fatality rate was 21% (57 of 274 cases).
      Six of the deaths were avoidable. The fatality rates for admission Glasgow Coma
      Scores of 3-5, 6-8 and over 9 were 81%, 21% and 3% respectively. Two patients
      died of infection complicating open depressed fractures. The case fatality rate
      for extradural haematoma was 20% and subdural haematoma 67%. Nine patients died
      of associated abdominal injuries. Most of the deaths were unavoidable because of
      the severity of primary brain injury. The speed of diagnosis and quality of care
      could have been improved but the most important area is management of the airway.
      General surgeons properly trained in trauma care (which includes emergency airway
      management) are well able to cope with the majority of head-injured patients in
      Papua New Guinea.

PMID- 9599980
TI  - The St John Ambulance Service in Port Moresby: a ten-year review, 1984-1993.
AB  - The National Capital District (NCD) is unique within Papua New Guinea in having a
      professional ambulance service which provides emergency care during transfer to
      hospital. This service has been run by St John Ambulance, who have maintained
      records of their work during their first ten years of operation. To review the
      operation of the service and to consider its potential for other parts of Papua
      New Guinea these records were transferred to a database and analyzed. The results
      of this analysis, together with relevant background, are presented and some of
      the issues which emerge are discussed. There have been heavy demands on the
      ambulance service to provide a taxi service for transferring patients between
      health facilities. Cancelled calls have also been a heavy drain on the service.
      Pregnancy-related requests for transport, including home deliveries, constitute
      the major group of emergency calls. Requests for transfer of patients with an
      acute medical or surgical condition requiring skilled attention provide an
      important part of the nonobstetrical work of the service, though this group makes
      up only 10% of the total number of requests. Trauma contributed 26% of the
      nonobstetrical emergency work of the service. The rate of requests for the
      population of the NCD has decreased and it is suggested that this is due to
      greater access to private vehicles rather than a decrease in demand for emergency
      transport. It is apparent that a skilled ambulance service cannot be provided
      cheaply, although for 1993 at 15 kina per request, or 30 kina if only the
      emergency requests are considered, the service is clearly efficient. Providing a
      similar service to other parts of Papua New Guinea with lower population
      densities and less sealed road would be very much more expensive. It is unlikely
      that the health services could approximate a similar degree of cost-efficiency to
      that of St John.

PMID- 9599981
TI  - Burns admissions to Port Moresby General Hospital 1978-1984.
AB  - A retrospective survey of 169 burns cases admitted to Port Moresby General
      Hospital was conducted for the period 1978 to 1984. A third of the patients were
      young children. Hot-water burns were the commonest type of injury, accounting for
      43%. This was followed by accidental falls into a fire and suicidal kerosene
      burns, which accounted for 28% and 13% respectively. Post-burn contractures were
      the commonest long-term complications. Prevention of burns is theoretically very
      attractive but hard to achieve in rural and squatter populations who rely almost
      entirely on open fires for cooking and heating. Burns awareness campaigns by all
      government and community groups stressing the dangers of open fires and leaving
      children unattended would no doubt take a long time but might ultimately produce
      tangible results.

PMID- 9599982
TI  - Changing trends in tribal fights in the highlands of Papua New Guinea: a five
      year review.
AB  - Tribal warfare is a way of life in the highlands of Papua New Guinea. In earlier
      times direct confrontation with bushknives and axes, and shooting with bows and
      arrows were common. In recent years there have not been as many instances of
      direct confrontation with bushknives and axes, but the use of bows and arrows is
      on the rise. Since 1993, guns have been increasingly used, with devastating
      results. In 1993, 18 deaths were reported from tribal warfare in one area of the
      Southern Highlands Province, especially from gunshots, while in 1994, 24 deaths
      were reported from another area. A five-year review of tribal fight admissions to
      Mendi Hospital, from 1990 to 1994, showed an increase in the number and
      proportion of gunshot wounds; there were none in 1990-1992 but they constituted
      18% of tribal fight injuries in 1993 and 33% in 1994.

PMID- 9599984
TI  - Management of vascular trauma in a provincial hospital.
AB  - Three cases of major vessel injuries referred to Mendi Hospital during 1993-1994
      are reported. All three vessels were repaired successfully. The surgical
      management of these cases is described.

PMID- 9599983
TI  - Trauma in Papua New Guinea: what do we know and where do we go?
AB  - Trauma is a major health problem in Papua New Guinea. Injuries are the commonest
      cause of death in the productive age group of 15-44 years. Trauma is the leading
      cause of surgical death in Port Moresby General Hospital. The common causes of
      injury are road traffic accidents, domestic violence, criminal assault, tribal
      fights, accidents at home and at work, burns and falls. This review summarizes
      what has been published on the different causes of trauma in Papua New Guinea.
      Though much has been written little has been done to implement the
      recommendations made. Papua New Guinea needs a spinal unit and it needs burns
      units in its major hospitals. There should be better facilities for
      rehabilitation. Little has been done to curb tribal fighting and domestic
      violence. Road traffic fatalities have at least remained static in the last
      decade and wearing seat belts is now compulsory, but the law must be enforced.
      Driving after drinking alcohol must be stopped and protective roll bars or cages
      must be fitted to all open-back utility vehicles which carry passengers. Progress
      requires vision and commitment by surgeons, leaders in public health, hospital
      administrators and politicians.

PMID- 9599985
TI  - Basis of molecular biology and its applications: II. An outline of common
      laboratory techniques used in molecular biology.

PMID- 9599986
TI  - The treatment of hand injuries.
AB  - A major hand injury can completely change a person's life. The consequences of
      the injury can be reduced by proper assessment, appropriate treatment and careful
      follow-up. Whenever experienced help is available then it should always be
      sought. This article describes the management of hand injuries. In Papua New
      Guinea the worst disasters occur when injuries are missed on initial assessment
      and the patient is not referred to a surgeon. Another common cause of poor
      outcome is failure to splint the hand in the correct position.

PMID- 9599987
TI  - Conservative management of femoral shaft fractures.

PMID- 9599988
TI  - Can we continue to justify the fight fee?

PMID- 9599989
TI  - Talker-specific learning in speech perception.
AB  - The effects of perceptual learning of talker identity on the recognition of
      spoken words and sentences were investigated in three experiments. In each
      experiment, listeners were trained to learn a set of 10 talkers' voices and were
      then given an intelligibility test to assess the influence of learning the voices
      on the processing of the linguistic content of speech. In the first experiment,
      listeners learned voices from isolated words and were then tested with novel
      isolated words mixed in noise. The results showed that listeners who were given
      words produced by familiar talkers at test showed better identification
      performance than did listeners who were given words produced by unfamiliar
      talkers. In the second experiment, listeners learned novel voices from sentence
      length utterances and were then presented with isolated words. The results showed
      that learning a talker's voice from sentences did not generalize well to
      identification of novel isolated words. In the third experiment, listeners
      learned voices from sentence-length utterances and were then given sentence
      length utterances produced by familiar and unfamiliar talkers at test. We found
      that perceptual learning of novel voices from sentence-length utterances improved
      speech intelligibility for words in sentences. Generalization and transfer from
      voice learning to linguistic processing was found to be sensitive to the talker
      specific information available during learning and test. These findings
      demonstrate that increased sensitivity to talker-specific information affects the
      perception of the linguistic properties of speech in isolated words and
      sentences.

PMID- 9599990
TI  - The perception of surface curvature from optical motion.
AB  - Observers viewed the optical flow field of a rotating quadric surface patch and
      were required to match its perceived structure by adjusting the shape of a
      stereoscopically presented surface. In Experiment 1, the flow fields included
      rigid object rotations and constant flow fields with patterns of image
      acceleration that had no possible rigid interpretation. In performing their
      matches, observers had independent control of two parameters that determined the
      surface shape. One of these, called the shape characteristic, is defined as the
      ratio of the two principle curvatures and is independent of object size. The
      other, called curvedness, is defined as the sum of the squared principle
      curvatures and depends on the size of the object. Adjustments of shape
      characteristic were almost perfectly accurate for both motion conditions.
      Adjustments of curvedness, on the other hand, were systematically over-estimated
      and were not highly correlated with the simulated curvedness of the depicted
      surface patch. In Experiment 2, the same flow fields were masked with a global
      pattern of curl, divergence, or shear, which disrupted the first-order spatial
      derivatives of the image velocity field, while leaving the second-order spatial
      derivatives invariant. The addition of these masks had only negligible effects on
      observers' performance. These findings suggest that observers' judgments of three
      dimensional surface shape from motion are primarily determined by the second
      order spatial derivatives of the instantaneous field of image displacements.

PMID- 9599991
TI  - Symmetry in haptic and in visual shape perception.
AB  - Four experiments tested the hypothesis that bilateral symmetry is an incidental
      encoding property in vision, but can also be elicited as an incidental effect in
      touch, provided that sufficient spatial reference information is available
      initially for haptic inputs to be organized spatially. Experiment 1 showed that
      symmetry facilitated processing in vision, even though the task required
      judgments of stimulus closure rather than the detection of symmetry. The same
      task and stimuli failed to show symmetry effects in tactual scanning by one
      finger (Experiment 2). Experiment 3 found facilitating effects for vertically
      symmetric open stimuli, although not for closed patterns, in two-forefinger
      exploration when the forefingers had previously been aligned to the body midaxis
      to provide body-centered spatial reference. The one-finger exploration condition
      again failed to show symmetry effects. Experiment 4 replicated the facilitating
      effects of symmetry for open symmetric shapes in tactual exploration by the two
      (previously aligned) forefingers. Closed shapes again showed no effect. Spatial
      reference information, finger movements, and stimulus factors in shape perception
      by touch are discussed.

PMID- 9599992
TI  - The use of different orientation cues in vernier acuity.
AB  - The role of orientation cues in vernier acuity was investigated in five
      experiments that varied the salience of different possible reference systems: (1)
      retinal, (2) subjective (vestibular), and (3) stimulus-defined ("intrinsic"). We
      compared the eight possible combinations of presence and absence of the three
      types of information about vertical by changing the orientation of the vernier
      stimulus, by changing the angle between the two segments of the stimulus, by
      reducing the stimulus to two dots rather than two lines, and/or by tilting the
      subject's head or by having the subject lie in a supine position. The results
      show that vestibular vertical plays no important role in vernier discriminations,
      whereas retinal vertical and, to a lesser degree, the intrinsic reference do. A
      control experiment excluded the possible role of a fourth possible reference
      system, the frame of the monitor. Our results are compatible with a model of
      vernier acuity detection based on oriented receptive fields with inhibitory
      surrounds. They show further that observers can produce, in the case of two-dot
      stimuli, an internal standard for comparison and detect deviations from this
      standard with high precision.

PMID- 9599993
TI  - Mapping symbols to response modalities: interference effects on Stroop-like
      tasks.
AB  - Response compatibility effects were assessed with a Stroop-like task which
      involved arrow and word stimuli. The subjects were required to respond to one
      stimulus--an arrow (e.g.,-->) or a word (e.g., left)--and ignore the other. It
      was shown that response compatibility played a significant role in generating
      Stroop-like interference. Robust interference effects were observed when the
      subjects responded manually to word stimuli (ignoring irrelevant arrows) and when
      they responded vocally to arrow stimuli (ignoring irrelevant words). Smaller
      interference effects were observed under response-compatible conditions, namely,
      responding manually to arrows and vocally to words. In the second experiment,
      within-dimension displays (e.g., arrow-arrow or word-word displays) yielded a
      pattern of interference that did not interact with response modality. These
      findings indicate that both stimulus-response compatibility effects and target
      distractor similarity are crucial for understanding Stroop-like interference.

PMID- 9599994
TI  - The start-stop procedure: estimation of temporal intervals by human subjects.
AB  - In four experiments investigating human timing, subjects produced estimates of
      sample durations by bracketing their endpoints. On each trial, subjects
      reproduced a sample duration by pressing a button before the estimated sample
      duration elapsed (start time) and releasing it after the estimated duration
      elapsed (stop time). From these responses, middle time (start + stop/2) and
      spread time (stop - start) were calculated, representing the point of subjective
      equality and the difference limen, respectively. In all experiments, subjects
      produced middle times that varied directly with sample duration. In Experiment 2,
      middle times lengthened when feedback was withheld. Consistent with Weber timing,
      spread times, as well as the standard deviation of middle times, varied directly
      with middle time (Experiments 1, 3, and 4). On the basis of an internal clock
      model of timing (Gibbon & Church, 1990), the data permitted inferences regarding
      memory processes and response threshold. Correlations between start and stop
      times and between start and spread times agreed with earlier findings in animals
      suggesting that the variance of temporal estimates across trials is based in part
      upon the selection of a single temporal memory sample from a reference memory
      store and upon one or two threshold samples for initiating and terminating each
      estimate within a trial.

PMID- 9599995
TI  - Do the magnocellular and parvocellular visual pathways contribute differentially
      to subitizing and counting?
AB  - We investigated the neurobiological basis of visual processes involved in object
      enumeration. Subitizing, the ability to rapidly and accurately enumerate four or
      fewer objects, is thought to depend on preattentive processing of visual stimuli,
      whereas counting of more numerous objects is thought to require serial shifts of
      attention. We attempted to distinguish between the hypothesis that the
      magnocellular (M) visual pathway is the preferential route for subitizing, and
      the alternative hypothesis that there is no selectivity for the M pathway or its
      counterpart, the parvocellular (P) visual pathway, in visual object enumeration.
      Green rectangles were presented on an equiluminant red background to impair M
      pathway processing. This slowed enumeration performance relative to a control
      condition in which object/background luminance differed, especially when the
      rectangles were relatively large and widely spaced and had constant retinal
      eccentricity. When low luminance contrast was used to impair processing along the
      P pathway, enumeration performance was slowed relative to a high-contrast control
      condition, especially when the rectangles were small and closely spaced. Overall,
      our manipulations affected enumeration performance without selectivity for
      subitizing or counting ranges and without altering the slope of the functions
      relating reaction time to numerosity. Thus, our results favor the hypothesis that
      visual enumeration does not depend preferentially on either the M or the P
      pathway.

PMID- 9599996
TI  - Effects of modality on subjective frequency estimates and processing of spoken
      and printed words.
AB  - Previous research (Garber & Pisoni, 1991; Pisoni & Garber, 1990) has demonstrated
      that subjective familiarity judgments for words are not differentially affected
      by the modality (visual or auditory) in which the words are presented, suggesting
      that participants base their judgments on fairly abstract, modality-independent
      representations in memory. However, in a recent large-scale study in Japanese
      (Amano, Kondo, & Kakehi, 1995), marked modality effects on familiarity ratings
      were observed. The present research further examined possible modality
      differences in subjective ratings and their implications for word recognition.
      Specially selected words were presented to participants for frequency judgments.
      In particular, participants were asked how frequently they read, wrote, heard, or
      said a given spoken or printed word. These ratings were then regressed against
      processing times in auditory and visual lexical decision and naming tasks. Our
      results suggest modality dependence for some lexical representations.

PMID- 9599997
TI  - Delayed commitment in spoken word recognition: evidence from cross-modal priming.
AB  - Using the cross-modal priming paradigm, we attempted to determine whether
      semantic representations for word-final morphemes embedded in multisyllabic words
      (e.g.,/lak/in /hemlak/) are independently activated in memory. That is, we
      attempted to determine whether the auditory prime, /hemlak/, would facilitate
      lexical decision times to the visual target, KEY, even when the recognition point
      for /hemlak/ occurred prior to the end of the word, which should ensure
      deactivation of all lexical candidates. In the first experiment, a gating task
      was used in order to ensure that the multisyllabic words could be identified
      prior to their offsets. In the second experiment, lexical decision times for
      visually presented targets following spoken monosyllabic primes (e.g., /lak/-KEY)
      were compared with reaction times for the same visual targets following
      multisyllabic pairs (/hemlak/-KEY). Significant priming was found for both the
      monosyllabic and the multisyllabic conditions. The results support a recognition
      strategy that initiates lexical access at strong syllables (Cutler & Norris,
      1988) and operates according to a principle of delayed commitment (Marr, 1982).

PMID- 9599998
TI  - Characteristics of anisometropic suppression: simple reaction time measurements.
AB  - The characteristics of artificially induced anisometropic suppression were
      investigated in observers with normal and abnormal binocular vision
      (anisometropic amblyopia) by using a simple reaction time paradigm. Reaction time
      was measured as a function of stimulus intensity for various stimulus durations.
      For all conditions, the reaction time increased as stimulus intensity decreased
      toward threshold. We found that traditional techniques for modeling this trend
      were inadequate, so we developed a simple visuogram method for comparing these
      functions. Using this technique, reaction time versus intensity functions are
      shown to be shape-invariant for all conditions examined. This means that,
      although reaction times are longer during induced anisometropic suppression or in
      anisometropic amblyopia, they are the same if contrast is normalized to equate
      threshold. The shape-invariant nature of these functions is also consistent with
      the notion that a single mechanism mediates detection under these conditions.
      Temporal summation was investigated at both threshold (method of limits) and
      suprathreshold (criterion reaction time) levels. Again, because of shape
      invariance, the suprathreshold results mirror the threshold results. The critical
      duration (the duration at the intersection of the complete summation and zero
      summation regions) is not affected by any of the conditions. However, the
      critical intensity (the intensity for the zero summation region) is higher for
      the amblyopic eyes, as compared with the normal or nonamblyopic eyes. Induced
      anisometropic suppression always increases the critical intensity, with a smaller
      increase occurring for the amblyopic eyes. This suggests that amblyopic eyes do
      not have a need for strong suppression.

PMID- 9599999
TI  - Adaptation is automatic.
AB  - Two experiments were used to test whether selective adaptation for speech occurs
      automatically or instead requires attentional resources. A control condition
      demonstrated the usual large identification shifts caused by repeatedly
      presenting an adapting sound (/wa/, with listeners identifying members of a /ba/
      /wa/ test series). Two types of distractor tasks were used: (1) Subjects did a
      rapid series of arithmetic problems during the adaptation periods (Experiments 1
      and 2), or (2) they made a series of rhyming judgments, requiring phonetic coding
      (Experiment 2). A control experiment (Experiment 3) demonstrated that these tasks
      normally impose a heavy attentional cost on phonetic processing. Despite this,
      for both experimental conditions, the observed adaptation effect was just as
      large as in the control condition. This result indicates that adaptation is
      automatic, operating at an early, preattentive level. The implications of these
      results for current models of speech perception are discussed.

PMID- 9600000
TI  - Discriminability in length of lines in the Muller-Lyer figure.
AB  - Receiver-operating characteristics for the discriminability in the length of the
      lines of the Muller-Lyer figure were obtained by the rating method of detection
      theory. Six observers judged the shaft length of the lines of the figure with
      reference to the same standard line. Maximum-likelihood estimates of the index of
      discriminability, d', were linear function of the difference in the length of the
      lines, but the functions did not pass through the origin because of a constant
      error of judgment. Because discriminability was determined by ROC analysis, the
      constant error could not be attributed solely to changes in criterion placement;
      instead, it showed that the Muller-Lyer figure induced a change in the
      discriminability of the lines.

PMID- 9600001
TI  - The trajectory of a dot crossing a pattern of tilted lines is misperceived.
AB  - The straight trajectory of a dot crossing a pattern of tilted lines is perceived
      as being sinusoidal. Manipulation of the size of the angle between the trajectory
      and the tilted lines, the velocity of the dot, and the distance between the
      tilted lines shows that the magnitude of the illusion is inversely proportional
      to the size of the incidence angle, to velocity, and to the distance between the
      lines. The illusion is interpreted as being the result of an integration process
      of local distortions occurring at the intersections with the tilted lines.

PMID- 9600002
TI  - [Psychotherapy under evaluation].

PMID- 9600003
TI  - [Self-recognition in the mirror of another? On the significance of cognitive
      neuroscience for psychoanalysis].
AB  - Current concepts in cognitive neuroscience are presented: neuroimaging,
      connectionism, models for visual perception and memory. Encountering a
      convergence of certain concepts like the one for memory between cognitive
      neuroscience and psychoanalysis makes it necessary to compare the framework
      assumptions underlying these concepts in each discipline. As it turns out, only a
      change away from the traditional functionalist framework to a modern, externalist
      form of non-reductionism makes it possible to use the theoretical convergences in
      a coherent manner. Conceptual consequences of this change in framework
      assumptions are discussed, particularly for the role of (neuronal) causes versus
      reasons in the explanation of behaviour within a broadly psychoanalytic context.

PMID- 9600004
TI  - [Psychotherapy and psychoanalysis in patient management: results of the
      Heidelberg Catamnesis Project].
AB  - In the "Heidelberg Long Term Psychotherapy Follow-up Project", a naturalistic
      study design, all types of treatment were included that had been performed at the
      Psychosomatic Clinic of the University of Heidelberg for a certain period
      (combined inpatient and outpatient individual and group therapy, as well as
      outpatient dynamic psychotherapies and psychoanalyses). The specific value of
      this project is due to the fact that--apart from many other, for instance
      psychological, assessment evaluations--three to five individual therapy goals had
      been predetermined for each patient before starting the treatment (goal
      attainment scaling). After the end of therapy and at the time of follow-up (3.5
      years later on the average), attainment of these goals was assessed by an
      independent rater. A total of 208 patients were examined who were evaluated
      according to their diagnosis (neurotic, functional or psychosomatic disorders)
      and the kind of treatment. With regard to symptomatology, individual therapy
      goals, psychological assessment and patient satisfaction, the overall results
      were good, partly very good, and were almost invariably stable during the long
      follow-up period. Two particular results are discussed separately: 1. As far as
      symptomatology was concerned, the group of psychoanalysis patients could not
      maintain the good outcome at the end of therapy during the long follow-up period.
      2. Patients with "psychosomatic disorders" attained remarkably good results,
      particularly if the treatment had initially been an inpatient setting.

PMID- 9600005
TI  - [Determinants of high risk illness behavior in patients with bronchial asthma].
AB  - The aim of this study was to identify factors influencing high-risk illness
      behaviour in patients with bronchial asthma. High-risk illness behaviour was
      defined as 1. non-compliance with antiasthmatic medication and 2. delaying or
      avoiding medical help when facing airways deterioration or severe attacks. 150
      patients with bronchial asthma were investigated; 60 of them had participated in
      the structured Asthma Treatment and Teaching Programme (ATTP), 90 had not taken
      part in such a programme by then. Using structural equation models, lack of
      emotional support by a key figure, poor doctor-patient relationship, and a
      negative cortisone image were identified as predictors of high-risk illness
      behaviour in patients who had attended ATTP, while in patients without
      participation in a treatment and teaching programme, only a negative cortisone
      image was predictive of this criterion.

PMID- 9600006
TI  - [Narration of illness and handicap].
AB  - The article argues for a narrative approach to subjective experience of illness
      and disability. Within the epistemological framework of discursive psychology,
      narrative presentations in social contexts are regarded as interactive practices
      of identity constitution and coping in the course of autobiographical
      construction. Possible contributions of a narratological approach to research on
      illness experience and coping as well as therapeutic and didactic consequences
      are discussed.

PMID- 9600007
TI  - [Individual significance and growing complexity: contributions of Sigmund Freud
      and Rene Spitz to developmental psychology].
AB  - Contributions of Sigmund Freud and Rene Spitz to developmental psychology are
      presented in terms of today's research. The work of each of these pioneers draws
      our attention to the need for increasing our knowledge about the meaning of
      individual experience and increasing complexity in the course of development.
      Freud's contribution to today's developmental thinking is reviewed in terms of
      his observations of play, his schematic perspectives on developmental processes,
      and his innovative theoretical approaches involving nonconscious mental activity
      in the context of constructivism. Spitz's contribution to today's thinking is
      reviewed according to a similar array of topics. These include his observational
      assessments of infants, his schematic perspectives on developmental processes,
      and his innovative theoretical approaches involving affective communications in
      the context of caregiving.

PMID- 9600008
TI  - [Introduction to attachment theory and its significance for psychotherapy].
AB  - In the first part of this article we give a review of the basic concepts of
      attachment theory and summarize Bowlby's crucial thoughts about attachment. In
      the second part we introduce the traditional attachment methods with concrete
      cases. In this context we describe the transgenerational aspect of attachment and
      highlighten the bridge between infant attachment and adult attachment
      representation. Further we give a critical review about adult attachment
      measures. In the third part we consider implications of attachment theory in
      respect to psychopathology and psychotherapy.

PMID- 9600009
TI  - [Co-responsibility in suicide? Coping with grief and guilt by Johann Wolfgang von
      Goethe].
AB  - Under the presumption of having promoted some young people's suicides by
      publishing his novel "Werther", Goethe was deeply affected by the suicide of
      Christiane von Lassberg, the 28-year old daughter of a Weimarian officer. The
      subject of this essay is to investigate how Goethe worked on the mental conflict
      of guilt and grief and how he counteracted the danger of paralysing depressions
      by active intervention and which form of literary expressions he chose.

PMID- 9600010
TI  - Effects of veratridine on sodium currents and fluxes.
AB  - Veratridine causes Na+ channels to stay open during a sustained membrane
      depolarization by abolishing inactivation. The consequential Na+ influx, either
      by itself or by causing a maintained depolarization, leads to many secondary
      effects such as increasing pump activity, Ca2+ influx, and in turn exocytosis. If
      the membrane is voltage clamped in the presence of the alkaloid, a lasting
      depolarizing impulse induces, following the "normal" transient current, another
      much more slowly developing Na+ current that reaches a constant level after a few
      seconds. Repolarization then is followed by an inward tail current that slowly
      subsides. Development of these slow currents is enhanced by additional treatment
      with agents that inhibit inactivation. Most of these phenomena can be
      satisfactorily explained by assuming that Na+ channels must open before
      veratridine binds to them, and that the slow current changes reflect the kinetics
      of binding and unbinding. It is unclear, however, where the alkaloid stays when
      it is not bound. Although the effect sets in promptly, once this pool is filled,
      access to it from outside must be impeded since in most preparations veratridine
      can only partially be washed out. Cooling acts as if the available concentration
      is reduced, but this reversible "reduction" takes much longer to develop than the
      cold-induced changes in kinetics. Several authors assume that the binding site,
      site 2, is accessed from the lipid phase of the membrane. Considerations of this
      kind are often based on experiments with batrachotoxin, the widely used site-2
      ligand which has a much higher affinity and acts as a full agonist in contrast to
      the partial agonist veratridine. Batrachotoxin thus lends itself to binding
      studies using radiolabeled derivatives. Such experiments may eventually lead to
      the characterization of neurotoxin site 2; the first promising steps have been
      taken. Modern techniques of molecular biology will almost certainly be
      successful, and one hopes for point-mutated channels with distinctly different
      reactions also to veratridine. A considerable amount of research is still
      required to clarify the structural basis for the numerous allosteric interactions
      with other sites, the mechanism of the very large potential shift of activation,
      the reduced single-channel conductance and selectivity, and the chemical nature
      of the different affinities of the site-2 toxins. Note Added in Proof. A report
      on point mutations with effects on neurotoxin site 2 (see Sect. 8) has just
      appeared: Wang S-Y, Wang GK (1988) Point mutations in segment I-S6 render voltage
      gated Na+ channels resistant to batrachotoxin. Proc Natl Acad USA 95:2653-2658.
      In microliter muscle Na+ channels expressed in mammalian cells, mutation
      Asn434Lys leads to complete, Asn434Ala to partial insensitivity to 5 mM
      batrachotoxin. (Asn434 corresponds to Asn419 of Trainer et al. 1996). The mutant
      channel displays almost normal current kinetics and in the presence of
      veratridine little, if any, slow tail current. However, veratridine inhibits peak
      Na+ currents in the mutant which may point to a complex structure of site 2.

PMID- 9600011
TI  - The elucidation of somatostatin receptor functions: a current view.

PMID- 9600012
TI  - Cytokine-mediated hepatic apoptosis.

PMID- 9600013
TI  - Expanded programme on immunization (EPI). Recrudescence of measles.

PMID- 9600014
TI  - Nutrition. The Innocenti Declaration: monitoring implementation in Europe. Part
      III.

PMID- 9600015
TI  - [What is your diagnosis? Coronary heart disease after inferior infarct].

PMID- 9600016
TI  - [Cancer--a disease of the genes].

PMID- 9600017
TI  - [Fibromyalgia (generalized tendomyopathy) in expert assessment. Analysis of 158
      cases].
AB  - MEDAS-agencies are medical institutions within the Swiss Disability Insurance,
      which specialize in assessing the working capacity of candidates who apply for a
      disability pension. Degenerative and other chronic pain disorders of the
      musculoskeletal system form the majority of cases that we investigate.
      Fibromyalgia is one of our most frequent diagnoses (8.6%). We become involved in
      cases on average 8.5 years after the first onset of painful symptoms and on
      average 2.5 years after the patients have ceased to work. Our experience, tells
      us that fibromyalgia is usually associated with psychological disturbances; thus
      our psychiatrists have found important psychological problems in 86.7% of
      applicants. They found mainly neurotic and depressive syndromes. Our
      investigations have shown that psychological disturbances precede the onset of
      musculoskeletal pain in about 70% of patients. Therefore, we don't consider
      fibromyalgia syndrome as an entity of its own, but regard it as a pain syndrome
      in which there are underlying psychological problems in most cases.

PMID- 9600018
TI  - [Determining diagnosis and therapy control of hypertension by time-limited loan
      of blood pressure monitors to patients. A report of experiences with acceptance
      and practical applications of the procedure in general practice].
AB  - Data from an investigation on acceptance and practicability of a temporary self
      assessment of blood pressure values including 181 patients of a rural practise
      are presented. Cooperation of the total collective was surprisingly good although
      particularly those patients with most risk factors revealed deficits in
      fulfilling the preconceived goals. Compared to 24 hour blood pressure monitoring
      total drop out rate in the self assessment group was lower (6.6%) although the
      requirement for involvement and cooperation was increased in this group. On an
      average about 39 blood pressure measurements have been performed by each patient.
      In the protocol six measurements per day over a period of 8 days were scheduled,
      amounting to a total number of single data recorded by experience of other
      authors to be sufficient for a valid assessment of the real blood pressure
      situation of each patient. In view of this proof of a satisfying cooperation and
      the relatively low costs of this method we believe that, according to our
      personal experience, this method (temporary blood pressure monitoring with rented
      blood pressure apparatus) may be recommended to every family doctor interested in
      adequate blood pressure diagnosis. As the investigation demonstrated the efforts
      caused by this method are low and do not interfere with usual activities in the
      office of a family doctor. On the other hand the pedagogic effect on the patient
      may not be underestimated.

PMID- 9600019
TI  - [Central lung embolism in chronic interstitial pneumopathy].
AB  - An 80 year old patient with known interstitial pneumopathy of unknown etiology
      was hospitalized because of acute onset and rapid deterioration of dyspnea at
      rest within days. A foregoing neurologic investigation including CT and EEG
      because of prior syncopes and cramp attacks had not revealed pathologic findings.
      Thorax X-ray at admission showed homogenous loss of transparency on the left
      side, calcified basal plaques on both sides and prominent central pulmonary
      vessels with jumping caliber. A punctate of the leftsided pleural effusion
      revealed lymphocytic exsudate, normal pH, low glucose and an elevated LDH. The
      patient died shortly after a collapse at a bowel visit and pulmonary embolism was
      suspected in accordance to results from arterial blood gas analysis, ECG and
      chest X-ray. Neurologic symptoms could be explained by recurrent pulmonary
      embolism. Pleural plaques together with the punctate suggested a malignant
      etiology. A mesothelioma was taken into consideration, although there were no
      anamnestic reports on an exposition to asbestos. Autopsy revealed almost complete
      central embolism of the left pulmonary artery with acute cor pulmonale thus
      confirming the clinical suspicion. The embolus showed components of different
      ages of origin. Besides bronchitic and emphysematous alteration histology of the
      pulmonary tissue revealed interstitial and septal fibrosis with focal tissue
      consolidation. In one giant cell a typical asbestos body was found (in 1 out of
      10 sections). In spite of missing information on an exposition to asbestos an
      abnormally high exposition must be taken into consideration because of the
      finding of an asbestos particle in relation to the amount of tissue studied.
      Apart from interstitial fibrosis asbestos may also cause consolidation of
      pulmonary tissue. Histology of plaquelike lesions revealed mesothelioma of
      fibrous type. This finding supports the suspicion that a major part of the
      pulmonary lesions was due to exposition to asbestos.

PMID- 9600020
TI  - [Cardiovascular arrest in adrenal cortex insufficiency].
AB  - We describe the case of a 55 year old patient with acute adrenal insufficiency
      who suffered from abdominal pain, recurrent syncope and cardiac arrest. 32 hours
      after the successful cardio-pulmonal resuscitation, the patient developed a
      catecholamine resistant hyperdynamic shock. With the initiation of prednisolone
      therapy, because of suspected acute adrenal insufficiency, catecholamines became
      effective and led to a hemodynamic stabilisation and a general amelioration of
      the patient. Glucocorticoids have a permissive function for catecholamines and
      therefore are essential in these situations. After fluid replacement acute
      adrenal insufficiency may present as hyperdynamic shock which can be confounded
      with septic shock. Cardiac arrest however is an unusual complication of Addison's
      disease and the responsible pathological mechanism is unknown.

PMID- 9600021
TI  - [General practice case. Trichuris trichiura intestinal infection].

PMID- 9600022
TI  - Integrative cardiac revitalization: bypass surgery, angioplasty, and chelation.
      Benefits, risks, and limitations.
AB  - Coronary artery disease (CAD) is still the main cause of premature death in the
      industrialized world. The revascularization modalities, bypass surgery and
      angioplasty, when successful provide restored blood flow to the myocardium.
      Bypass remains the most proven means for managing more severe cases of CAD,
      namely triple vessel disease with or without complications, while angioplasty
      works best for cases of single or double vessel disease with minimal
      complications. Both types of intervention partially relieve angina as they clear
      arterial blockage. Both save lives to an extent greater than medication alone.
      However, both are limited to being palliative since they fail to treat the
      underlying atherosclerotic occlusive process. EDTA chelation therapy appears to
      achieve revitalization of the myocardium, and is a viable alternative or adjunct
      to revascularization. Fish oils are now proven to help revitalize vessel wall
      endothelia and to partially reverse atherosclerotic damage. Being safe and having
      proven benefits, chelation therapy and fish oils can be integrated together with
      nutrients, lifestyle-dietary revision, exercise, and medications as necessary,
      into a cardiovascular revitalization strategy. Cardiovascular revitalization
      would be highly cost-effective and procedurally compatible with the
      revascularization modalities, while extending beyond revascularization to halt
      atherosclerotic progression, restore cardiac functionality, extend survival, and
      improve quality of life.

PMID- 9600024
TI  - The role of glucosamine sulfate and chondroitin sulfates in the treatment of
      degenerative joint disease.
AB  - Successful treatment of osteoarthritis must effectively control pain, and should
      slow down or reverse progression of the disease. Biochemical and pharmacological
      data combined with animal and human studies demonstrate glucosamine sulfate is
      capable of satisfying these criteria. Glucosamine sulfate's primary biological
      role in halting or reversing joint degeneration appears to be directly due to its
      ability to act as an essential substrate for, and to stimulate the biosynthesis
      of, the glycosaminoglycans and the hyaluronic acid backbone needed for the
      formation of proteoglycans found in the structural matrix of joints. Chondroitin
      sulfates, whether they are absorbed intact or broken into their constituent
      components, similarly provide additional substrates for the formation of a
      healthy joint matrix. Evidence also supports the oral administration of
      chondroitin sulfates for joint disease, both as an agent to slowly reduce
      symptoms and to reduce the need for non-steroidal anti-inflammatory drugs. The
      combined use of glucosamine sulfate and chondroitin sulfates in the treatment of
      degenerative joint disease has become an extremely popular supplementation
      protocol in arthritic conditions of the joints. Although glucosamine sulfate and
      chondroitin sulfates are often administered together, there is no information
      available to demonstrate the combination produces better results than glucosamine
      sulfate alone.

PMID- 9600023
TI  - St. John's Wort (Hypericum perforatum): clinical effects on depression and other
      conditions.
AB  - St. John's Wort (Hypericum perforatum), a perennial flowering plant, has been
      used medicinally for thousands of years, and has most recently been identified as
      an effective treatment for mild to moderate depression. Clinical studies on the
      use of this plant for depression have utilized liquid tinctures and standardized
      solid extracts (0.3% hypericin--300 mg three times a day). Severe depression may
      also respond to this botanical, although it appears a larger dose is needed (600
      mg solid extract three times a day). Hypericum has been favorably compared to
      numerous antidepressant drugs, the studies having revealed equivalent results and
      a much more favorable incidence of side effects. Studies have also demonstrated
      its efficacy in treating seasonal affective disorder. In vitro investigations of
      Hypericum show antiviral activity, although there is evidence these promising
      results might not occur in vivo. Traditional actions and uses include enhancement
      of wound healing, as well as anti-inflammatory and analgesic activity.

PMID- 9600025
TI  - AIDS wasting syndrome as an enterometabolic disorder: the gut hypothesis.
AB  - There is an interesting relationship between the HIV virus, the health of the
      gastrointestinal tract, and AIDS wasting syndrome, involving Tumor Necrosis
      Factor alpha (TNF alpha), specific and non-specific immunity in the gut, gut
      permeability, and oxidative stress. It is hypothesized that the progression of
      HIV to full-blown AIDS may be impacted by maintaining a healthy gut. A
      therapeutic protocol which decreases oxidative stress, inhibits TNF alpha,
      enhances phase I and II liver detoxification, and improves specific and non
      specific immunity in the gut should be part of a therapeutic protocol for HIV
      infected individuals. Through a better understanding of the pathophysiology of
      HIV advancing to AIDS, the practitioner can develop a treatment strategy of
      nutritional and lifestyle changes which could theoretically prevent an HIV
      infection from advancing to full-blown AIDS.

PMID- 9600027
TI  - Coenzyme Q10.

PMID- 9600026
TI  - Ginkgo biloba.

PMID- 9600029
TI  - Heart disease. Therapy spurs growth of blood vessels.

PMID- 9600028
TI  - Americans and red meat: a love-hate relationship.

PMID- 9600030
TI  - High blood pressure. Lifestyle changes replace drugs for some.

PMID- 9600031
TI  - Herbal supplements. Is saw palmetto good for the prostate?

PMID- 9600032
TI  - Antioxidants. Vitamin E may cut prostate cancer risk.

PMID- 9600033
TI  - "I've heard that testosterone can boost a woman's libido. Is it safe to take male
      hormones"?

PMID- 9600034
TI  - Acetaminophen and warfarin.

PMID- 9600035
TI  - Calcium blockers questioned.

PMID- 9600036
TI  - Eight suggestions for '98.

PMID- 9600038
TI  - Weight loss: the secrets of success.

PMID- 9600037
TI  - Managing menopause: an update.

PMID- 9600039
TI  - Zooming in on zinc.

PMID- 9600040
TI  - Aerobics on wheels.

PMID- 9600041
TI  - A breath of fresh air for asthma patients.

PMID- 9600042
TI  - I read in your June 1997 publication that one of the risk factors for hip
      fracture is current use of long-acting benzodiazepines. Could you list exactly
      which medications these are? I take Xanax and doxepin for fibromyalgia. My
      pharmacist could find no evidence that either of these drugs depletes bone
      calcium. How do they place me at increased risk for osteoporosis?

PMID- 9600043
TI  - Recently, I heard on a TV show that anticholesterol drugs can cause hair loss.
      I've been taking Zocor for about 18 months now, and in the past 6 months I've
      noticed hair loss from the top and sides of my head. Is this common? Will my hair
      regrow once I stop taking the drug?

PMID- 9600045
TI  - Bouncing back from bad times.

PMID- 9600044
TI  - Folic acid fortification. Is it enough?

PMID- 9600046
TI  - Multiple sclerosis.

PMID- 9600049
TI  - Weighing in on Meridia.

PMID- 9600048
TI  - Knocking out knee pain.

PMID- 9600047
TI  - New approaches to PMS.

PMID- 9600050
TI  - Because I had a lumpectomy, chemotherapy, and radiation for breast cancer in
      1990, I am not a candidate for estrogen replacement therapy. One of my friends
      suggested that I should also avoid soy products because there is natural estrogen
      in them. This was news to me. Will the type and amount of estrogen in soy foods
      be detrimental to my future health?

PMID- 9600051
TI  - I have an embarrassing problem with earwax. My ears plug up and hurt. Is there
      some secret of personal hygiene that I missed? How can I prevent it?

PMID- 9600052
TI  - Getting the right cure for ulcers.

PMID- 9600053
TI  - Making sure you get enough calcium.

PMID- 9600055
TI  - Sidestepping foot problems, Part II.

PMID- 9600054
TI  - New solutions for urinary stress incontinence.

PMID- 9600056
TI  - How effective are Hyalgan injections for arthritis?

PMID- 9600057
TI  - Should I worry about a cough from taking an ACE inhibitor?

PMID- 9600058
TI  - Genes for sexual behavior.
AB  - The mating behavior of Drosophila melanogaster is a stereotyped sequence of fixed
      action patterns, composed of orientation, tapping, singing, licking, attempted
      copulation and copulation. Mutations that block a unique aspect of mating
      behavior were isolated and analyzed at the cellular and molecular levels. The
      wild-type counterparts of the mutated genes were shown to rescue the phenotypes
      by their ubiquitous or targeted expression in some of the mutants. This strategy
      of artificial control of fly behavior opens up an avenue for studies to identify
      the neural center for individual behavioral actions.

PMID- 9600059
TI  - Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4
      deficient mice.
AB  - The physiological role of the prostaglandin E2 receptor EP4 subtype was
      investigated by generation of EP4-deficient-mice by gene targeting. Loss of the
      EP4 receptor was not lethal in utero, but most EP4 (-/-) neonates became pale and
      lethargic approximately 24 h after birth and died within 72 h. Less than 5% of
      the EP4 (-/-) mice survived and grew normally more than a year. Histological
      examination revealed that the ductus arteriosus in dead neonates remained open,
      while it was partially closed in the survivors. In situ hybridization study
      showed that EP4 mRNA was strongly expressed in the ductus. These results suggest
      that neonatal death is at least partly due to patent ductus arteriosus and that
      the EP4 receptor plays a role in regulation of the patency of this vessel. They
      also indicate that normal function of the EP4 receptor is essential in neonatal
      adaptation of the circulatory system.

PMID- 9600060
TI  - Prompt activation of telomerase by chemical carcinogens in rats detected with a
      modified TRAP assay.
AB  - The maintenance of telomere length is crucial for survival of cells. Telomerase
      is an RNA-containing reverse transcriptase, which is responsible for elongation
      of shortened telomeres. Telomerase reactivation has been suggested to be involved
      in malignant progressions. To study on the involvement of telomerase activation
      in in vivo carcinogenesis, we first modified the original TRAP assay by changing
      the primer designs and the labeling method of PCR products to an end-labeling
      method. Second, we investigated the activation of telomerase in different organs
      after treatments of rats with various chemical carcinogens. Very early after the
      beginning of the treatment, telomerase activity in the liver, kidney, and lung
      was increased. In most cases, telomerase activation occurred in the primary or
      favorite target organs. The present results suggest that telomerase activation
      occurs promptly when animals are exposed to chemical carcinogens, which may
      contribute to in vivo chemical carcinogenesis.

PMID- 9600061
TI  - Genetic structure of the bphG gene encoding 2-hydroxymuconic semialdehyde
      dehydrogenase of Achromobacter xylosoxidans KF701.
AB  - 2-Hydroxymuconic semialdehyde dehydrogenase catalyzes the conversion of 2
      hydroxymuconic semialdehyde (HMS) to an enol form of 4-oxalocrotonate which is a
      step in the catechol meta-cleavage pathway. A bphG gene encoding HMS
      dehydrogenase of A. xylosoxidans KF701, a soil bacterium degrading biphenyl, was
      identified at between catechol 2,3-dioxygenase gene and HMS hydrolase gene, and
      its sequence was analyzed. An open reading frame (ORF) corresponding to bphG gene
      was consisted of 1461 nucleotides with ATG initiation codon and TGA termination
      codon. The ORF exhibited 66% of G + C content, and a putative ribosome-binding
      sequence, AGAGA, was identified at about 10 nucleotides upstream initiation codon
      of the bphG gene. The bphG gene can encode a polypeptide of molecular weight 52
      kDa containing 486 amino acid residues. A deduced amino acid sequence of HMS
      dehydrogenase encoded in bphG gene from A. xylosoxidans KF701 exhibited the
      highest 94% homology with that of corresponding enzyme encoded in xylG from P.
      putida mt-2, 63% to 90% homology with those of other reported HMS dehydrogenases,
      and 29% to 42% homology with those of betaine aldehyde dehydrogenase, 5-carboxy
      HMS dehydrogenase, aldehyde dehydrogenase, indole-3-acetaldehyde dehydrogenase,
      succinic semialdehyde dehydrogenase, methylmalonate semialdehyde dehydrogenase,
      and succinylglutamate 5-semialdehyde dehydrogenase. From an alignment of amino
      acid sequence of HMS dehydrogenase from A xylosoxidans KF701 with other reported
      dehydrogenases, putative cofactor NAD(+)-binding regions and catalytic residues
      were identified.

PMID- 9600062
TI  - Role of latent TGF-beta 1 binding protein in vascular remodeling.
AB  - Transforming growth factor-beta (TGF-beta) is secreted as a latent, high
      molecular weight complex, which is composed of TGF-beta, a latency associated
      peptide (LAP) and a latent TGF-beta binding protein (LTBP). In this study, we
      report on the role of LTBP in vascular remodeling. 0.01-5 ng/ml of LTBP
      stimulated the migration activities of cultured rat arterial smooth muscle cells
      (SMC) about 4-7 fold compared with control in vitro. The maximal activity of SMC
      migration by LTBP was 75% of that by 10 ng/ml of PDGF-BB. A checker board
      analysis showed that the migration by LTBP was chemotactic, not chemokinetic. By
      cross-linking experiment, LTBP associated with 80-120 kd cell surface protein of
      SMC, suggesting that a part of LTBP can bind with SMC. Furthermore, LTBP was more
      strongly expressed in the intimal layer than in the medial layer of BCI artery.
      These results suggest that LTBP plays an important role in the initial stage of
      arterial intimal thickening through the acceleration of SMC migration from the
      medial to intimal layer and is one of the essential factors influencing vascular
      remodeling.

PMID- 9600063
TI  - Occurrence of pyridoxal 5'-phosphate-dependent serine racemase in silkworm,
      Bombyx mori.
AB  - D-Serine is known to occur in the silkworm Bombyx mori as well as in the
      mammalian central nervous systems. We found that serine racemase occurs in the
      insect, catalyzing the conversion of L-serine to its antipode. The enzyme was
      partially purified from pupae of the insect, and was inactivated by treatment
      with hydroxylamine and reactivated with pyridoxal 5'-phosphate (PLP). L-Alanine
      was racemized slowly by the enzyme at a rate of only about 6% of that of L
      serine, and L-arginine and L-glutamine were inert as substrates. Therefore, the
      enzyme is a member of PLP-dependent amino acid racemases, and is distinct from
      alanine racemase (EC 5.1.1.1) and amino acid racemase with low substrate
      specificity (EC 5.1.1.10). This is the first report of the occurrence of serine
      racemase in eukaryotes producing D-serine.

PMID- 9600064
TI  - Identification of a potential substrate binding domain in the mammalian peptide
      transporters PEPT1 and PEPT2 using PEPT1-PEPT2 and PEPT2-PEPT1 chimeras.
AB  - The mammalian peptide transporters PEPT1 and PEPT2 are energized by a
      transmembrane electrochemical H+ gradient and exhibit similar broad substrate
      specificity. These transporters however differ in their affinity for substrates,
      PEPT1 being a low-affinity transporter and PEPT2 being a high-affinity
      transporter. To identify the substrate binding domain in PEPT1 and PEPT2 which is
      responsible for the differing affinities, we constructed a series of PEPT1-PEPT2
      and PEPT2-PEPT1 chimeras using an in vivo restriction site-independent procedure
      and determined their substrate affinities. A comparison of these kinetic data for
      different chimeras with those of the wild-type PEPT1 and PEPT2 in conjunction
      with the specific structural PEPT1/PEPT2 crossover regions in these chimeras has
      led to the identification of a putative substrate binding site, which is
      comprised of the transmembrane domains 7, 8 and 9 of the transporters.

PMID- 9600065
TI  - Different biochemical properties of nuclear and microsomal estrone-3-sulfatases:
      evidence for the presence of a nuclear isozyme.
AB  - In female rats, total estrone-3-sulfatase activity per liver in the nuclear
      fraction is comparable to the total activity per liver in the microsomal
      fraction. The combined estrone-3-sulfatase activity in the other fractions
      (lysosomal, mitochondrial, and cytosolic fractions) is negligible and only
      accounts for < 5% of the total nuclear or microsomal sulfatase activity. Nuclear
      and microsomal estrone-3-sulfatases have different pH optima (pH 8.0 and 7.2,
      respectively). The apparent Km values for the nuclear and microsomal estrone-3
      sulfatases are 2.5 and 10.1 microM, respectively, suggesting that the nuclear
      sulfatase has a considerably higher affinity for estrone-3-sulfate than the
      microsomal sulfatase. Moreover, the nuclear estrone-3-sulfatase is more sensitive
      to inhibition by several steroids than the microsomal sulfatase. The results
      suggest that estrone-3-sulfatase in the nuclear fraction is a different isozyme
      than that in the microsomal fraction.

PMID- 9600066
TI  - Novel CRE-binding proteins of 11-16 kDa bind to the LDH A-gene CRE in a sequence
      specific and hepatocyte-growth dependent manner in partially hepatectomized rat
      liver.
AB  - We examined cAMP response element (CRE)-binding proteins involved in lactate
      dehydrogenase A (LDHA)-gene transcription in rat liver after partial hepatectomy.
      Gel retardation and Southwestern blot assays showed that the CRE-binding activity
      of the 11-16 kDa novel proteins increased in accordance with increases in LDH A
      mRNA in regenerating liver tissues, whereas that of the 43 kDa CREB did not.
      Using CRE-oligonucleotide affinity chromatography and reverse-phase HPLC, we
      purified four CRE-binding proteins of 11.2, 15.2, 15.8, and 16.3 kDa. N-terminal
      amino acid sequences of 15.2 and 16.3 kDa proteins revealed a high sequence
      homology to but were not identical with those of rat histone H2A.1 and H2B,
      respectively. CRE-bindings of these two proteins were highly specific, while
      those of histones H2A.1 and H2B were nonspecific as shown by competition
      Southwestern blot and DNase I footprinting assays. Taking these data together, we
      suggest that the novel 11-16 kDa CRE-binding proteins are responsible for the
      cell growth-dependent inducibility of LDH A-gene transcription during liver
      regeneration.

PMID- 9600067
TI  - The role of p38 MAP kinase in TGF-beta1-induced signal transduction in human
      neutrophils.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is the strongest chemoattractant
      yet described for human neutrophils. It activates neither phospholipase C nor
      phospholipase D. It does not induce rises in intracellular calcium,
      degranulation, or superoxide production. The signaling pathways utilized by TGF
      beta 1 are largely unknown. This report demonstrates that TGF-beta 1 activates
      p38 MAP kinase. The kinase inhibitor SB203580 blocks the chemotactic responses as
      well as actin polymerization induced by TGF-beta 1. Potential cellular targets of
      the p38 MAP kinase pathway which could mediate these function are discussed.

PMID- 9600068
TI  - pICln can regulate swelling-induced Cl- currents in either layer of rabbit
      ciliary epithelium.
AB  - Swelling-induced Cl- currents were investigated in freshly prepared non-pigmented
      epithelial (NPE) and pigmented epithelial (PE) cells of the rabbit ciliary body
      using the whole-cell patch clamp technique. Exposure of both NPE and PE cells to
      hypotonic stress induced Cl- currents that exhibited outward rectification and
      were insensitive to Ca+2. We found that swelling-induced Cl- currents in PE cell
      are observed shortly after isolation. The swelling-induced Cl- current showed
      little or no inactivation at positive membrane voltages and was sensitive to 100
      microM NPPB and 100 microM DIDS. Injection of cRNA encoded rabbit pICln into
      Xenopus oocytes produced an outwardly rectifying Cl- current displaying features
      consistent with the swelling-induced Cl- current in epithelium. pICln is
      ubiquitous in the ciliary epithelium. It participates in the equilibration of
      short term tonicity alterations, a phenomenon underlying mechanisms with larger
      and slower amplitudes for aqueous secretion by these cells.

PMID- 9600069
TI  - Ultraviolet B suppresses vitamin D receptor gene expression in keratinocytes.
AB  - Keratinocytes not only produce vitamin D3 in response to ultraviolet B light
      (UVB) and convert 25-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3
      (1,25(OH)2D) but also possess the vitamin D receptor (VDR) and respond to
      1,25(OH)2D. We characterized the regulation of the expression of the VDR gene in
      primary human keratinocytes following UVB irradiation. We report a marked dose
      dependent down-regulation of the VDR mRNA and protein within a few hours after
      irradiation. This occurs independently of de novo protein synthesis and is not
      due to a change in the half-life of the VDR mRNA. Interestingly, treatment of the
      cells with sodium salicylate, caffeic acid phenethyl ester and
      tosylphenylchloromethylketone inhibited this down-regulation. Our results
      strongly suggest the existence of a feedback mechanism in that UVB initiates
      vitamin D synthesis in keratinocytes and at the same time limits VDR abundance.
      They also provide a rational explanation for the reported lack of any additive
      effect between 1,25(OH)2D and UVB phototherapy in the treatment of psoriasis.

PMID- 9600070
TI  - Bradykinin stimulates the tyrosine phosphorylation and bradykinin B2 receptor
      association of phospholipase C gamma 1 in vascular endothelial cells.
AB  - Bradykinin (BK) B2 receptor signaling involves activation of phospholipase C
      (PLC). PLC activation by other receptors consists of either allosteric activation
      of PLC beta isoforms by G-proteins or tyrosine phosphorylation of PLC gamma
      isoforms. Because the B2 receptor is a G-protein-coupled receptor, it has been
      assumed that the receptor signals through PLC beta. In the present study,
      however, we have found that BK stimulation of IP3 production and the Ca2+ signal
      in endothelial cells is dependent on tyrosine phosphorylation. Furthermore,
      stimulation of B2 receptors in these cells is accompanied by a transient tyrosine
      phosphorylation of PLC gamma 1. Phosphorylation is correlated with increased IP3
      production and association of PLC gamma 1 with the C-terminal intracellular
      domain of the B2 receptor. The B2 receptor can thus physically associate with
      intracellular proteins other than G-proteins. Activation of PLC gamma isoforms,
      rather than PLC beta isoforms, may, therefore, be primarily responsible for BK
      stimulated IP3 generation in endothelial cells.

PMID- 9600071
TI  - Polyoma middle T antigen activates the Ser/Thr kinase Akt in a PI3-kinase
      dependent manner.
AB  - Polyoma middle T antigen (PMT) was originally identified as the tumorigenic
      component of the polyomavirus genome. To investigate whether the serine/
      threonine kinase Akt/PKB, which is the proto-oncogene transduced by the
      transforming AKT8 retrovirus, is activated by PMT, 3T3-L1 fibroblasts were stably
      transfected with wild type PMT. PMT expression accelerated glucose transport and
      increased phosphorylation of p70 S6-kinase and MAPK. PMT expression also
      stimulated Akt kinase activity 7 fold as compared to untreated, mock infected
      cells. This stimulation rivaled that obtained following insulin treatment of both
      mock and PMT infected cells. Akt activation and phosphorylation were eliminated
      in a PMT mutant incapable of interacting with PI3-kinase, but not one which does
      not interact with Shc, and correlated closely to the amount of PI3-kinase
      activity in anti-phosphotyrosine immunoprecipitates. These results indicate that
      the PI3-kinase pathway is requisite, but the Shc pathway is dispensable, for Akt
      activation. The studies further suggest that Akt may participate in PMT and PI3
      kinase's regulation of cellular transformation and tumorigenesis.

PMID- 9600072
TI  - Cloning and characterization of a novel class I cytokine receptor.
AB  - The human gp130 cDNA sequence was used as a query to search an expressed sequence
      tag database (dbEST) to identify cDNA sequences with similarity to the cytokine
      class I receptor family. A novel class I cytokine receptor was identified in a
      human infant brain cDNA library and was named WSX-1. Full-length cDNA sequences
      for human and murine WSX-1 were isolated and characterized. The WSX-1 cDNA
      encodes a 636 amino acid transmembrane protein with an extracellular domain of
      482 amino acids and a cytoplasmic domain of 96 amino acids. The structure of the
      WSX-1 protein most closely resembles that of gp130. Northern blot analysis
      indicates high levels of expression in thymus, spleen, lymph node, and peripheral
      blood leukocytes, suggesting a role for WSX-1 in modulation of the immune
      response.

PMID- 9600073
TI  - The neuropeptide Y/peptide YY Y1 receptor is coupled to MAP kinase via PKC and
      Ras in CHO cells.
AB  - The neuropeptide Y/peptide YY (PYY) Y1 receptor subtype mediates proliferative
      responses. This report identifies effector molecules which mediate mitogen
      activated protein kinase (MAPK) phosphorylation by Y1 receptor activation in
      transfected CHO cells. Pertussis toxin pretreatment abolishes this effect,
      indicating involvement of Gi or G(o) proteins. Inhibition of protein kinase C
      (PKC) also blocks PYY-induced MAPK phosphorylation. Additionally in this cell
      model PYY causes an increase in GTP binding to Ras protein, and cotransfection of
      dominant negative constructs for Ras and Raf blocks PYY effects on MAPK. These
      data suggest a novel mechanism for Y1 receptor coupling to MAPK, which is at once
      pertussis toxin-sensitive as well as PKC- and Ras-dependent.

PMID- 9600074
TI  - Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2.
AB  - Vascular endothelial growth factor (VEGF) binds to its receptor tyrosine kinase
      Flt-1 and KDR/Flk-1 and stimulates their autophosphorylation. However, little is
      known about their downstream signal transduction properties. We examined the
      interactions of certain proteins with a SH2-domain with Flt-1 and KDR using the
      yeast two-hybrid system and found that Nck, SHP-2, PLC gamma, and PI3K p85 bind
      to Flt-1. Extensive site-directed mutagenesis of Flt-1 revealed their major
      binding sites. Nck, SHP-2, and PI3K bind to Y1213 of Flt-1. Nck also binds to
      Y1333 of Flt-1. These results suggest that Nck, SHP-2, PLC gamma, and PI3K play
      important roles in Flt-1 signal transduction and that Y1213 of Flt-1 is a major
      binding site of PI3K, Nck, and SHP-2.

PMID- 9600075
TI  - Detection and discrimination of PrPSc by multi-spectral ultraviolet fluorescence.
AB  - Prion diseases are progressive degenerative disorders of the central nervous
      system. The transmissibility and fatal nature of these diseases necessitate their
      rapid and accurate diagnosis. The hallmark of these diseases is the accumulation
      of PrPSc, a protease-resistant form of a host-coded glycoprotein. We have been
      evaluating the use of multi-spectral ultraviolet fluorescent spectroscopy as a
      means of detecting and distinguishing between different forms of PrPSc.
      Spectroscopic measurements of fluorescence from untreated and proteinase K (PK)
      treated PrPSc, purified from 263K scrapie strain-infected hamster brains and ME7
      scrapie strain-infected mouse brains, were performed. Spectra of untreated and PK
      treated PrPSc samples for 263K and ME7 appeared qualitatively different. The
      identification and discrimination of PrPSc were possible based on these spectral
      signatures, calculations of their fluorescence cross sections, and determination
      of the orthogonal differences. This technique has the potential not only for the
      sensitive, specific, and direct detection of PrPSc, but also for the ability to
      distinguish between different forms of the prion protein.

PMID- 9600076
TI  - Irreversible telomere shortening by 3'-azido-2',3'-dideoxythymidine (AZT)
      treatment.
AB  - Telomeres shorten by 30 to 50 bp with each cell division. Germ line, tumor and
      stem cells overcome progressive shortening by elongating their telomeres with
      telomerase. Previously we demonstrated that 3'-azido-2',3'-dideoxythymidine
      (AZT), incorporates into telomeric DNA. To determine if telomeric AZT
      incorporation was a telomerase mediated phenomenon, we subjected tumor cells to
      long-term AZT exposure. Here we report the shortening of the telomeric sequences
      of HeLa cells cultured with 800 microM AZT for 15 passages. Southern blots of
      HeLa DNA cultured with AZT and digested with SAU 3AI, Alu I, and Rsa I revealed a
      progressive shortening of the telomeric repeats when probed with a human
      biotinylated telomeric probe. The shortened telomeric repeats did not elongate
      after culturing without AZT for an additional 25 passages. No evidence of
      senescence could be detected.

PMID- 9600077
TI  - Extracellular Mg2+ inhibits both histamine-stimulated Ca(2+)-signaling and
      exocytosis in human tracheal secretory gland cells.
AB  - The effects of extracellular Mg2+ concentration have been investigated on the
      histamine-stimulated exocytotic process of human tracheal secretory gland (HTG)
      cells. The exocytosis of secretory granules (SG) was observed concomitantly with
      dynamic changes of intracellular Ca2+ ([Ca2+]i) and Mg2+ concentrations
      ([Mg2+]i). The rate of SG exocytosis was appraised by the decrease of quinacrine
      fluorescence emission. Dynamic changes of [Mg2+]i and [Ca2+]i in HTG cells were
      determined by the combined use of UV-microspectrofluorometry with Mag-Indo-1 and
      Indo-1 probes, respectively. High Mg2+ medium significantly inhibited the
      histamine-stimulated secretion. The influence of the extracellular and
      intracellular Mg2+ concentrations on [Ca2+]i was analyzed. Basal [Mg2+]i
      increased from 0.8 mM in a Mg(2+)-free medium to 1.7 mM in 10 mM Mg2+ medium.
      Histamine induced a [Mg2+]i increase which is dependent on extracellular Mg2+
      concentration. The histamine stimulated [Ca2+]i rise was reduced in the presence
      of elevated Mg2+ extracellular medium and inhibitory effects of extracellular
      Mg2+ were concomitant with changes in [Mg2+]i. Our data suggest that the
      inhibition by extracellular Mg2+ of stimulated exocytosis is dependent on both
      the increase of [Mg2+]i and the inhibition of cytosolic Ca2+ influx.

PMID- 9600078
TI  - Sequential interaction of CD4 and HIV-1 gp120 with a reconstituted membrane patch
      of ganglioside GM3: implications for the role of glycolipids as potential HIV-1
      fusion cofactors.
AB  - The fusion of HIV-1 with CD4+ cells involves, in addition to CD4, specific cell
      surface molecules acting as fusion cofactors. Recently, we reported that the V3
      loop of HIV-1 gp120 binds to GM3, a ganglioside abundantly expressed on CD4+
      lymphocytes and macrophages. In the present study, we show that CD4 interacts
      with a reconstituted patch of GM3 by measuring the surface pressure with a
      Langmuir film balance. A biphasic increase in surface pressure is observed after
      the sequential addition of CD4 and gp120 under the GM3 monolayer, indicating the
      formation of the trimolecular complex GM3-CD4-gp120. Neutralization of gp120 with
      an anti-V3 antibody inhibits the secondary interaction with GM3, suggesting that
      the CD4-induced conformational change in gp120 allows the V3 loop to interact
      with GM3. In conclusion, this study supports the concept that glycolipids can
      function as HIV-1 fusion cofactors.

PMID- 9600079
TI  - Expression of Ets-1 transcription factor in relation to angiogenesis in the
      healing process of gastric ulcer.
AB  - Ets-1 is a transcription factor known to control the expression of genes involved
      in extracellular matrix remodeling. The purpose of this study is to evaluate the
      expression of Ets-1 in the process of healing of ulceration in the rats. The time
      dependent changes and distribution of Ets-1 in the margins of ulcer were
      examined. Ets-1 did not express in the normal gastric mucosa. In the marginal
      granulation tissue, fibroblasts and endothelial cells of capillaries were
      immunopositive for Ets-1. Ets-1 expression was significantly increased at the
      early phase, and returned to normal levels at the scarred phase. Serial
      sectioning revealed that fibroblasts and endothelial cells also expressed MMP-1.
      Protein levels and mRNA expression of Ets-1 were confirmed by Western blotting
      and RT-PCR. These findings suggest that Ets-1 plays an important role in
      angiogenesis in the early phase of ulcer healing.

PMID- 9600080
TI  - Dissociation between the inhibitory and stimulatory effects of opioid peptides on
      cAMP formation in SK-N-SH neuroblastoma cells.
AB  - Opioid agonists either potentiate or suppress basal cAMP production in SK-N-SH
      cells. The inhibitory effect is mediated by PTX-sensitive GTP-binding proteins,
      while the stimulatory effect involves Ca++ entry and calmodulin activation. Both
      pathways can be activated simultaneously by opioid agonists. Low (nM)
      concentrations of either mu (DAMGO) or delta (DPDPE) selective opioids potentiate
      cAMP formation. At higher (100 nM) concentrations, however, a net suppression
      takes over; this suppression can be eliminated by PTX, and the underlying
      stimulatory effect is disclosed. Micromolar concentrations of either mu or delta
      selective agonists cross-activate the other (delta or mu) receptors, and augment
      the stimulatory pathway. The overall outcome (either stimulation or inhibition of
      cAMP production) is dependent on the balance between the two overlapping
      pathways, and can be modified by blocking either of the two opposing mechanisms.

PMID- 9600081
TI  - Thrombopoietin induces tyrosine phosphorylation of a common beta subunit of GM
      CSF receptor and its association with Stat5 in TF-1/TPO cells.
AB  - TF-1/TPO cells are derived from an erythroleukemia cell line, TF-1, and are
      absolutely dependent on either TPO or granulocyte-macrophage colony-stimulating
      factor (GM-CSF)/interleukin-3 (IL3) for their continuous growth and survival. To
      gain insight into the molecular basis of hemopoietic activities shared by TPO and
      GM-CSF/IL3 in TF-1/TPO cells, we studied the cross-talk between signal
      transduction pathways elicited by these cytokines. Stimulation of TF-1/TPO cells
      with TPO resulted in tyrosine phosphorylation of the TPO receptor (c-Mpl) as well
      as the common beta subunit (beta c) of GM-CSF/IL3 receptor complex. GM-CSF,
      however, induced tyrosine phosphorylation of beta c but not c-Mpl. TPO-induced
      tyrosine phosphorylation of beta c was time- and dose-dependent. We next examined
      whether or not TPO-induced tyrosine phosphorylation of beta c led to recruitment
      of SH2-containing molecules such as Stat5 and Shc. While GM-CSF caused
      association of Stat5 and Shc with beta c, TPO caused association of Stat5, but
      not Shc, with beta c, suggesting that TPO and GM-CSF may not induce
      phosphorylation of the same sets of tyrosine residues in beta c. These results
      suggest that activation of c-Mpl affects the signaling pathway of GM-CSF/IL3 but
      not vice versa.

PMID- 9600083
TI  - A novel isoform of rat estrogen receptor beta with 18 amino acid insertion in the
      ligand binding domain as a putative dominant negative regular of estrogen action.
AB  - A novel isoform of rat estrogen receptor (ER) beta, ER beta 2, which is a
      putative alternative splicing product of the reported ER beta (ER beta 1) has
      been identified. Rat ER beta 2 cDNA contains an additional, in-frame 54 base pair
      insertion in the ligand binding domain of ER beta 1, which generates an 18 amino
      acid residue insertion. Northern blot and RT-PCR analyses revealed that ER beta 2
      coexists with ER alpha and ER beta 1 in all tissues examined including brain,
      lung, liver, kidney, fat, bone, uterus, prostate, and ovary. The insertion caused
      loss of ligand binding activity of ER beta 2, whereas the ability to bind the
      palindromic estrogen response element (ERE) was retained. In an ERE-containing
      luciferase reporter gene assay using COS-1 cells, ER beta 2 failed to activate
      estrogen-dependent transcription. Furthermore, ER beta 2 dose dependently
      suppressed the ER alpha- and ER beta 1-mediated transcriptional activation. These
      results suggest that rat ER beta 2 functions as a negative regulator of estrogen
      action.

PMID- 9600082
TI  - Non-histone chromosomal proteins HMG1 and 2 enhance ligation reaction of DNA
      double-strand breaks.
AB  - DNA ligase IV in a complex with XRCC4 is responsible for DNA end-joining in
      repair of DNA double-strand breaks (DSB) and V(D)J recombination. We found that
      non-histone chromosomal high mobility group (HMG) proteins 1 and 2 enhanced the
      ligation of linearized pUC119 DNA with DNA ligase IV from rat liver nuclear
      extract. Intra-molecular and inter-molecular ligations of cohesive-ended and
      blunt-ended DNA were markedly stimulated by HMG1 and 2. Recombinant HMG2-domain
      A, B, and (A + B) polypeptides were similarly, but non-identically, effective for
      the stimulation of DSB ligation reaction. Ligation of single-strand breaks
      (nicks) was only slightly activated by the HMG proteins. The DNA end-binding Ku
      protein singly or in combination with the catalytic component of DNA-dependent
      protein kinase (DNA-PK) as the DNA-PK holoenzyme was ineffective for the ligation
      of linearized pUC119 DNA. Although the stimulatory effect of HMG1 and 2 on
      ligation of DSB in vitro was not specific to DNA ligase IV, these results suggest
      that HMG1 and 2 are involved in the final ligation step in DNA end-joining
      processes of DSB repair and V(D)J recombination.

PMID- 9600084
TI  - Type II domains of BSP-A1/-A2 proteins: binding properties, lipid efflux, and
      sperm capacitation potential.
AB  - Bovine seminal plasma contains a family of major proteins (collectively called
      1BSP proteins) that potentiate sperm capacitation by binding to capacitation
      factors such as heparin and by stimulating sperm membrane cholesterol efflux.
      Here, we investigated the structure-function relationship of type II domains of
      BSP proteins. We isolated from a tryptic digest of citraconylated BSP-A1/-A2
      proteins the intact second type II domain (domain b or Db). Similar to native
      protein, Db bound to heparin-Sepharose, p-aminophenylphosphorylcholine-Agarose
      and liposomes containing phosphatidylcholine. When assessed for biological
      function, Db did not stimulate cholesterol efflux from human fibroblasts, a cell
      model for lipid efflux studies, and from bovine spermatozoa, or potentiate bovine
      sperm capacitation induced by heparin and high-density lipoproteins. Therefore,
      type II motifs of BSP proteins represent binding units for sperm membrane choline
      phospholipids and heparin but the second type II domain of BSP-A1/-A2 alone is
      not sufficient to stimulate lipid efflux nor is sufficient to potentiate bovine
      sperm capacitation. Thus, the presence of both type II domains in BSP proteins is
      essential for the expression of functional properties, namely lipid efflux and
      sperm capacitation.

PMID- 9600085
TI  - Pro-neurotensin/neuromedin N expression and processing in human colon cancer cell
      lines.
AB  - The regulatory peptide neurotensin NT has been proposed to exert an autocrine
      trophic effect on human colon cancers. In the present study, pro
      neurotensin/neuromedin N (proNT/NN) expression and processing were investigated
      in 13 human colon cancer cell lines using a combination of radioimmunoassay and
      HPLC techniques. All 13 cell lines displayed low to moderate levels of proNT/NN
      ranging from 10 to 250 fmol/mg protein. However, only 6 (HCT8, LoVo, HT29, C119A,
      LS174T, and coloDM320) processed the precursor. Three of the latter (HCT8,
      LS174T, and coloDM320) were analysed in detail with regard to proNT/NN processing
      pattern and were found to produce NT and large precursor fragments ending with
      the NT or NN sequence. They had no detectable level of NN. Such a processing
      pattern resembles that generated by the prohormone convertase PC5. Northern and
      Western blot analysis of prohormone convertase expression in the 3 cell lines
      revealed that they were devoid of PC1 and PC2, whereas they all expressed PC5.
      These data indicate that proNT/NN is a good marker of human colon cancer cell
      lines while NT is found in only about half of the cell lines. They also suggest
      that, in addition to NT, several proNT/NN-derived products, possibly generated by
      PC5, might exert an autocrine positive effect on human colon cancer growth.

PMID- 9600086
TI  - The antiviral activity of a synthetic peptide derived from the envelope SU
      glycoprotein of feline immunodeficiency virus maps in correspondence of an
      amphipathic helical segment.
AB  - In a previous paper (Lombardi et al., Virology 220, 274-284, 1996), we-reported
      that a 20-amino acid synthetic peptide derived from a conserved region of the SU
      glycoprotein of feline immunodeficiency virus (FIV), i.e.,
      225EGPTLGNWAREIWATLFKKA244, bound the surface of FIV-permissive cells and
      inhibited FIV infection of CrFK and lymphoid cells. In this paper, we report, by
      the use of N- and C-terminus deleted synthetic analogs and by glycine scanning
      experiments that the minimal sequence needed for the full antiviral activity of
      the peptide maps in correspondence of amino acids 229LGNWAREIWATL240 and that
      either tryptophans residues at sequence position 232 or 237 are essential for
      such activity. Circular dichroism (CD) studies indicate that in the presence of a
      hydrophobic environment the 225E-A244 peptide adopts a structure containing an
      amphipathic alpha-helical segment of approximately 7 residues, corresponding to 2
      helical turns, likely in correspondence of the sequence 231(N)WAREIW(A)238. Such
      a helical segment of FIV SU glycoprotein may play a role in viral envelope fusion
      role with the host cell membrane, thus proving critical for cell infection.

PMID- 9600087
TI  - Protein kinase C isoform expression and function in transformed and non
      transformed pancreatic acinar cell lines.
AB  - Members of the protein kinase C (PKC) family of multifunctional serine/threonine
      phosphorylating enzymes are believed to play a role in regulating cellular
      differentiation and proliferation in many cell types. In the present study, we
      examined the expression of PKC isoforms in non-transformed (BMRPA.430) and
      transformed (TUC3) rat pancreatic acinar cell lines and compared this to PKC
      expression in freshly dispersed acini from rat pancreas. BMRPA.430 cells maintain
      characteristics of normal acini and are not tumorigenic, whereas TUC3 cells do
      not express tight junctions or polygonal morphology and are tumorigenic. As
      reported previously, PKC alpha, delta, epsilon, and zeta are expressed in freshly
      prepared acini. Likewise, these isoforms were detected in both the BMRPA.430 and
      TUC3 cell lines. In addition, PKC theta, a novel isoform, was detected in all
      three cell types at low levels. We used two PKC inhibitors to examine the role of
      PKC in acinar cell proliferation. CGP 41 251, a selective PKC inhibitor, and Go
      6976, an agent which specifically inhibits calcium-dependent PKC isoforms,
      inhibited cell proliferation of both cell lines. Translocation of PKC alpha to
      the membrane was not observed in either cell line. Hence, our data indicate that
      ras-induced transformation does not alter PKC isoform expression in pancreatic
      acinar cells and that activation of PKC alpha is involved with acinar cell
      growth.

PMID- 9600088
TI  - Phosphatidylinositol 3-kinase is required for the regulation of hepatitis B
      surface antigen production and mitogen-activated protein kinase activation by
      insulin but not by TPA.
AB  - Insulin suppresses hepatitis B surface antigen (HBsAg) gene expression and
      stimulates cell proliferation in human hepatoma Hep3B cells. 12-O-tetradecanoyl
      phorbol-13-acetate, TPA, has been demonstrated to mimic insulin actions in these
      cells. We examined the role of phosphatidylinositol 3-kinase (PI 3-kinase) in the
      signaling pathways of insulin and TPA towards these two biological phenomena in
      Hep3B cells. The pre-treatment of 5 microM of wortmannin diminished insulin
      suppressed HBsAg production and completely abolished insulin stimulated cell
      proliferation. However, wortmannin had no effect on TPA actions in both HBsAg
      suppression and cell growth stimulation. We further investigated the effect of
      wortmannin in mitogen-activated protein kinases (MAPKs) activation induced by
      insulin or TPA. After the pretreatment of wortmannin, insulin activated MAPKs was
      completely blocked, but TPA was still capable to activate MAPKs. These results
      suggest that PI 3-kinase is involved in insulin actions but not in TPA effects,
      and allow us to dissociate the signaling pathways of insulin and TPA in human
      hepatoma Hep3B cells.

PMID- 9600089
TI  - Molecular cloning and expression of Ehf, a new member of the ets transcription
      factor/oncoprotein gene family.
AB  - The ets family is a large multigene family of transcription factors that share a
      conserved DNA-binding "ETS" domain and include several oncoproteins that induce
      tumorigenesis when overexpressed. Here we report the cDNA cloning from mouse
      pituitary somatotroph tumors, sequence characterization and tissue-specific
      expression pattern in mice of a novel ets family gene, "Ehf" ("ets homologous
      factor"). The putative 300 amino acid Ehf protein is a highly divergent ets
      family member, but is most related to the recently identified oncoprotein ESX
      (36% overall and 84% ETS domain amino acid identity). Thus, Ehf and ESX comprise
      a new ets subfamily. Ehf is a single-copy gene, but produces four distinct mRNA
      transcripts. Ehf transcripts are abundant in mouse kidney and lung, less so in
      muscle and liver, and not detected in brain, spleen or testes. Because of its
      presence in somatotroph tumors and its relationship to ESX, Ehf may represent a
      new oncoprotein.

PMID- 9600090
TI  - Primary structure of ovine fibroblast growth factor-1 deduced by protein and cDNA
      analysis.
AB  - The amino acid sequence of full-length ovine fibroblast growth factor-1 (FGF-1)
      was determined by a combination of protein and cDNA sequencing. FGF-1 cDNA
      analysis indicated that ovine kidney cells express mRNAs encoding both full
      length FGF-1 and a truncated FGF-1 variant. An overall comparison of the ovine
      FGF-1 primary sequence to the eight species studied to date revealed a high
      degree of conservation, with ovine FGF-1 sharing 90 and 95% sequence identity
      with human FGF-1 and bovine FGF-1, respectively. Additionally, the FGF-1 proteins
      from the various species have conserved cysteine residues at positions 30 and 97
      and contain acetylated amino-terminal alanine residues. Mass spectrometry
      analysis confirmed that the blocking group of ovine FGF-1 is also consistent with
      that of an acetyl-moiety. In contrast to the other FGF-1 proteins, the 154
      residue primary sequence of ovine FGF-1 contains three unique amino acid
      differences: Arg9, Arg44, and Ile123. Ovine FGF-1, unlike human FGF-1, is a
      potent mitogenic factor for NIH 3T3 fibroblasts in the absence of heparin. In the
      presence of exogenous heparin, the mitogenic activity of ovine FGF-1 is
      potentiated slightly.

PMID- 9600091
TI  - Characterization of phorbolester-inducible human neuronal factors involved in
      trans-activation of the galanin gene.
AB  - The expression of the neuropeptide galanin (GAL) is elevated in vivo upon nerve
      stimulation, injury, and in vitro by phorbol 12-myristate-13-acetate (PMA),
      suggesting that a signal pathway involving protein kinase C activation may be
      involved in GAL-gene activation. When plasmids containing a different length of
      the bovine GAL-promoter fused to luciferase were transfected into the human
      neuroblastoma cell line (SK-N-SH subclone SH-SY5Y), a PMA-responsive element was
      identified in the promoter-region -68 to -46 base pairs (bp). Co-transfection
      experiments with plasmids expressing cJun and cFos revealed that they could act
      alone, as well as synergistically with PMA to induce luciferase activity.
      Electrical mobility shift assays revealed that a cAMP response element (CRE)-like
      sequence (TGACGCGG; -59 to -52 bp) bound PMA-inducible nuclear proteins present
      in SH-SY5Y cells. These proteins appear to bind mainly as CRE-binding
      protein/activating-transcription-factor (CREB/ATF) and Jun/ATF heterodimers. In
      addition, an apparent PMA-inducible protein(s) not recognized by CREB/ATF and Jun
      antibodies bound to the CRE-like containing probe.

PMID- 9600092
TI  - Osteoclast differentiation factor (ODF) induces osteoclast-like cell formation in
      human peripheral blood mononuclear cell cultures.
AB  - We have reported that osteoclast differentiation factor (ODF) expressed on the
      plasma membrane of osteoblasts/ stromal cells is a ligand for osteoclastogenesis
      inhibitory factor (OCIF). A genetically engineered soluble form of ODF (sODF)
      induced osteoclast-like multinucleated cells (OCLs) in the presence of M-CSF in
      mouse spleen cell cultures. Osteoblasts/stromal cells were not required in this
      process. To elucidate the mechanism of human osteoclastogenesis, human peripheral
      blood mononuclear cells (PBMCs) were cultured for 7 days with sODF and human M
      CSF in the presence or absence of dexamethasone. Treatment of human PBMCs with
      sODF together with M-CSF induced OCLs, which expressed tartrate-resistant acid
      phosphatase and vitronectin receptors, produced cAMP in response to calcitonin,
      and formed resorption pits on dentine slices. OCLs were also formed from the
      adherent cell population of human PBMCs. Dexamethasone was required for human OCL
      formation in culture of whole PBMCs but not in culture of the adherent cell
      population. OCL formation was strongly inhibited by OCIF simultaneously added.
      These results clearly indicate that like in mouse osteoclastogenesis, ODF is a
      critical factor for human osteoclastogenesis. The present study also indicates
      that OCIF acts as a naturally occurring decoy receptor for ODF in inhibiting
      signal transduction in human osteoclast formation.

PMID- 9600093
TI  - Identification and cloning of human G-protein gamma 7, down-regulated in
      pancreatic cancer.
AB  - Differentially expressed genes between normal and cancer tissues of the pancreas
      were investigated using differential display. Consequently, we identified a
      fragment cDNA that was expressed in the normal tissue but was rarely expressed in
      the cancer tissue. This cDNA was screened in cDNA library prepared from the
      normal pancreatic tissue by rapid amplification of cDNA ends (5'RACE). 859 bp of
      cDNA was cloned and sequenced, and the inferred amino acid sequence was found to
      encode a G protein gamma subunit with 98% homology to cow G protein gamma 7 and
      complete homology to human G protein gamma 7. The decreased expression of the G
      protein gamma 7 was confirmed by Northern blot assay in twelve pancreatic
      malignancies which included nine duct cell carcinomas, two cystoadenocarcinomas
      and one blastoma. Reverse transcriptase (RT)-polymerase chain reaction (PCR)
      assay showed no expression of G protein gamma 7 in five of six pancreatic
      carcinoma cell lines and two pancreatic cancer tissues. Immunohistochemical
      analysis also displayed positive staining in the normal tissue but no staining in
      the cancer tissue. The findings demonstrated that the reduced or suppressed
      expression of human G-protein gamma 7 may play an important role in pancreatic
      carcinogenesis.

PMID- 9600094
TI  - A new member of the amiloride-sensitive sodium channel family in Drosophila
      melanogaster peripheral nervous system.
AB  - Amiloride sensitivity is a common characteristic of structurally related cationic
      channels that are associated with a wide range of physiological functions. In
      Caenorhabditis elegans, neuronal and muscular degenerins are involved in
      mechanoperception. In animal epithelia, a Na(+)-selective channel participates in
      vectorial Na+ transport. In the snail nervous system, an ionotropic receptor for
      the peptide FMRFamide forms a Na(+)-selective channel. In mammalian brain and/or
      in sensory neurons, ASIC channels form H(+)-activated cation channels involved in
      nociception linked to acidosis. We have now cloned a new member of this family
      from Drosophila melanogaster. The corresponding protein displays low sequence
      identity with the previously cloned members of the super-family but it has the
      same structural organization. Its mRNA was detected from late embryogenesis (14
      17 hours) and was present in the dendritic arbor subtype of the Drosophila
      peripheral nervous system multiple dendritic (md) sensory neurons. While the
      origin and specification of md neurons are well documented, their roles are still
      poorly understood. They could function as stretch or touch receptors, raising the
      possibility that this Drosophila gene product, called dmdNaC1, could also be
      involved in mechanotransduction.

PMID- 9600095
TI  - Generation of a tropoelastin mRNA variant by alternative polyadenylation site
      selection in sun-damaged human skin and ultraviolet B-irradiated fibroblasts.
AB  - The goal of this research was to delineate the post-transcriptional mechanisms
      responsible for the increased elastin synthesis characteristic of sundamaged
      skin. In this study, a unique molecular variant of the tropoelastin mRNA
      transcript was identified in human sundamaged skin that was derived from the
      usage of an alternate polyadenylation site. Nonsolar exposed human skin expressed
      one tropoelastin mRNA species whereas sundamaged human skin expressed the primary
      tropoelastin mRNA and a larger, alternate tropoelastin mRNA formed from the
      utilization of a second polyadenylation site. Cultured human skin fibroblasts
      expressed both tropoelastin transcripts and in vitro UV treatment increased the
      amount of the unique tropoelastin mRNA. Hairless mouse skin (normal and UV
      treated) expressed the primary tropoelastin transcript although UV irradiation
      increased the length of its poly (A) tail two-fold. Therefore, UV radiation may
      stimulate elastin production by affecting polyadenylation site selection and the
      poly (A) tail length of tropoelastin mRNA.

PMID- 9600096
TI  - Identification of mouse ULK1, a novel protein kinase structurally related to C.
      elegans UNC-51.
AB  - A novel protein kinase related to the C. elegans serine/threonine kinase UNC-51
      was cloned from mouse. The UNC-51-Like Kinase (ULK)1 is encoded by a cDNA of 1051
      amino acids with calculated MW of 113 kDa. Comparison of the ULK1 and UNC-51
      shows the highest conservation in the amino-terminal kinase domain, which is
      followed by a proline/serine-rich (PS) domain and a conserved carboxyl-terminal
      (C) domain. ULK1 mRNA is expressed in various tissues, and is mapped to mouse
      chromosome 5F and rat chromosome 12q16.3, by fluorescent in situ hybridization.
      HA-tagged ULK1 is expressed as a protein of approximately 150 kDa in COS7 cells
      and is auto-phosphorylated in vitro in its PS domain. We propose that ULK1, UNC
      51 and a yeast protein kinase Apg1p comprise a novel subfamily of protein kinase,
      which is structurally conserved among eukaryotes.

PMID- 9600097
TI  - The electron affinities of the radicals formed by the loss of an aromatic
      hydrogen atom from adenine, guanine, cytosine, uracil, and thymine.
AB  - The major ion formed in Negative Ion Chemical Ionization Mass Spectrometry of
      Adenine, Guanine, Cytosine, Uracil and Thymine is the dehydrogenated anion. The
      CURES EC procedure for optimizing Austin Model-1 Multiconfigurational
      Configuration Interaction semi-empirical calculations is applied to the electron
      affinities of the corresponding dehydrogenated bases and N-H bond dissociation
      energies. These calculated values will be compared with literature values of the
      gas phase acidities of the purines and pyrimidines. The N-H bond dissociation
      energies are about 3.95 eV for Guanine, Adenine, and Thymine and 4.08 eV for
      Cytosine and Uracil. The electron affinities of the radicals are AMinH = 3.50 eV,
      GMinH = 3.46 eV, CMinH = 3.38 eV, UMinH = 3.48 eV, TMinH = 3.46 eV.

PMID- 9600098
TI  - Mitogenic effect of fibrinogen on hematopoietic cells: involvement of two
      distinct specific receptors, MFR and ICAM-1.
AB  - In addition to its well-known functions in blood clotting and cell adhesion,
      fibrinogen has been reported to be a mitogen for lymphoid cell lines and for
      human hematopoietic progenitors. Two specific receptors, the mitogenic fibrinogen
      receptor (MFR) and intercellular adhesion molecule-1 (ICAM-1/CD54), have been
      identified as possible candidates for the mediation of the mitogenic effect of
      fibrinogen. However, it has been questioned whether the MFR and ICAM-1 are truly
      distinct molecules. Using an antiserum specific for the MFR, we demonstrate that
      the MFR is a cell surface molecule clearly distinct from ICAM-1. Both receptors
      can be expressed separately or coexpressed on different cell types. Moreover,
      they are regulated differently: ICAM-1 is calcium-dependent whereas the MFR is
      not and the MFR is down-regulated by fibrinogen whereas ICAM-1 is not. The
      inhibition by an anti-MFR serum of the mitogenic effect of fibrinogen confirms
      the mitogenic function of the MFR.

PMID- 9600099
TI  - Multiple phosphorylation of chicken protein tyrosine phosphatase 1 and human
      protein tyrosine phosphatase 1B by casein kinase II and p60c-src in vitro.
AB  - We have cloned a soluble chicken protein tyrosine phosphatase, named CPTP1, from
      the cDNA library of chicken intestine. The CPTP1 showed 92% sequence identity to
      the corresponding 321 amino acid residues of human PTP1B (HPTP1B). CPTP1 lacked
      13 amino acids of the N-terminal region compared with HPTP1B, while the C
      terminal 48 amino acid sequence of this protein was distinct from those of other
      PTPs. In vitro phosphorylation and phosphoamino acid analysis showed that both
      CPTP1 and HPTP1B were phosphorylated on serine and threonine residues near their
      N-terminus by casein kinase II (CKII). Furthermore, phosphorylation of CPTP1 by
      CKII resulted in an inhibition of its phosphatase activity in vitro.
      Interestingly, both CPTP1 and HPTP1B were also tyrosine-phosphorylated near their
      N-terminus by p60c-src. When we examined the vanadate effect, in the absence of
      vanadate, the tyrosine-phosphorylated CPTP1 by p60c-src was autodephosphorylated
      by its own phosphatase activity. These results suggest that both CPTP1 and HPTP1B
      might play an important role in CKII- and p60c-src-induced signal transduction
      cascades.

PMID- 9600100
TI  - The proteasome is involved in angiogenesis.
AB  - The proteasome is a recently identified intracellular protease whose catalytic
      active site is a threonine residue and has been shown to play key roles in a
      variety of important intracellular events, including cell cycle progression, the
      antigen-presenting pathway, and apoptosis. However, its biological significance
      in multicellular organisms is still largely unknown because of lack of
      experimental systems for its study. Here we verified potential involvement of the
      proteasome in angiogenesis using lactacystin, a specific proteasome inhibitor.
      Lactacystin treatment resulted in almost complete prevention of in vivo
      neovascularization in the developing chick embryo chorioallantoic membrane. It
      also inhibited vascular endothelial tube formation on Matrigel, a model for in
      vitro angiogenesis, in a concentration-dependent fashion. Moreover, it prevented
      production of plasminogen activator, an important protease responsible for
      induction of angiogenesis, by endothelial cells, which correlated well with its
      suppression of intracellular proteasome activity. Our studies suggest that the
      proteasome operates in the process of angiogenesis, a phenomenon essential in
      important physiological and pathological settings.

PMID- 9600101
TI  - Insulin-induced translocation of protein kinase B to the plasma membrane in rat
      adipocytes.
AB  - Protein kinase B (PKB) has previously been shown to be activated in response to
      insulin and growth factor stimulation. The activation mechanism has been
      suggested to involve translocation of PKB to membranes, where it is
      phosphorylated and activated. Insulin-induced translocation of PKB has not been
      demonstrated in a physiological target cell. Therefore we have used the primary
      rat adipocyte to investigate insulin-induced translocation of PKB. In the
      presence of 1 nM insulin translocation of PKB was detected within 30 seconds and
      was blocked by wortmannin, a selective phosphatidylinositol 3-kinase inhibitor.
      This translocation was potentiated by the tyrosine phosphatase inhibitor
      vanadate. Subcellular localization studies revealed that PKB translocated to the
      plasma membrane.

PMID- 9600102
TI  - Increased hepatocyte growth factor production by aging human fibroblasts mainly
      due to autocrine stimulation by interleukin-1.
AB  - Hepatocyte growth factor (HGF), also known as scatter factor is a pleiotropic
      factor that is mainly produced by mesenchymal cells and acts on cells of
      epithelial origin which express the HGF receptor c-Met. Here we demonstrate that
      production of HGF by human embryonic lung fibroblasts increased sharply after
      about 70% completion of their lifespan in culture, which is regulated at the
      transcriptional level. In addition, human skin fibroblasts from old donors, over
      80 years, also produced more HGF than cells from young and middle-aged donors.
      The increased production of HGF by aging fibroblasts from human embryonic lung
      tissue is mainly due to autocrine stimulation by interleukin-1.

PMID- 9600103
TI  - Fine profile of actomyosin motility fluctuation revealed by using 40-nm probe
      beads.
AB  - The displacement of colloidal gold beads only 40 nm in diameter can be detected
      with spatial and temporal resolutions of 2.8 nm and 0.5 msec by using an optical
      setup in which two laser beams are reflected on the same field of a prism
      surface, forming interference fringes in an evanescent field adjacent to the
      prism surface, and the changes in scattering intensity that occur when the beads
      move across the fringes are measured in optical microscopic images. Results
      obtained when using this setup and actin-bound gold beads to measure the movement
      of actin filaments on myosin motor molecules revealed the fine profile of
      movement fluctuation and that the duty time of a single stroke of myosin motors
      is less than 10-20 milliseconds.

PMID- 9600104
TI  - A novel biomarker for hyperglycemia, MRX isolated from hydrolysate of glycated
      proteins.
AB  - Long-lived proteins can undergo non-enzymatic glycation to form highly
      crosslinked structures with characteristic fluorescence during aging and diabetes
      processes. In this paper, a typical fluorophore, named Maillard reaction product
      X (MRX), was isolated from the hydrolysate of glycated proteins. MRX could be
      formed by incubation of bovine serum albumin with glucose, followed by acid
      hydrolysis. The structure of MRX was determined to be 8-hydroxy-5
      methyldihydrothiazolo[3,2-alpha] pyridinium-3-carboxylate. MRX was also found to
      be formed by the incubation of cysteine and arginine with glucose, followed by
      hydrolysis. We found the formation of MRX in the recently developed genetically
      diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and compared them with
      that in the control Long-Evans Tokushima Otsuka (LETO) rats. Significantly higher
      levels of MRX were observed from the serum (p < 0.005) and urinary protein (p <
      0.001) of OLETF rats in comparison with those of LETO rats. MRX must be a
      potential candidate as a biomarker for hyperglycemia.

PMID- 9600105
TI  - A genetic and correlation analysis of liver cholesterol concentration in rat
      recombinant inbred strains fed a high cholesterol diet.
AB  - Liver cholesterol concentration in rats fed a high cholesterol diet, is under
      genetic control which is supported by significant differences observed among
      inbred strains. For instance, the Brown Norway (BN-Lx/Cub) rat developed a
      twofold higher liver cholesterol concentration than the spontaneously
      hypertensive rat (SHR/Ola). In the current study, we used 30 recombinant inbred
      (RI) strains, derived from BN-Lx and SHR progenitors, to locate quantitative
      trait loci (QTL) that are responsible for differences in liver cholesterol
      concentrations between the BN-Lx and SHR strains. The heritability of liver
      cholesterol was estimated to be 0.55 and a significant association was detected
      between concentration of liver cholesterol and the D10Cebrp1016s2 marker on
      chromosome 10 (lod score = 3.3); this putative QTL was responsible for nearly 64%
      of additive genetic variability and thus represents a major genetic determinant
      of liver cholesterol concentration. Liver cholesterol concentrations
      significantly correlated with intermediate density lipoprotein (IDL) cholesterol
      levels.

PMID- 9600106
TI  - Enhanced expression of Fas ligand is associated with aburatubolactam C-induced
      apoptosis in human Jurkat T cells.
AB  - The mechanism for apoptosis induced by aburatubolactam C was investigated in
      human Jurkat T cells. When the cells were treated with 3 micrograms/ml of
      aburatubolactam C, apoptotic DNA fragmentation was first detectable in 3 hr and
      then increased time-dependently in accordance with upregulation in the protein
      level of Fas ligand (FasL). Both the DNA fragmentation and upregulation of FasL
      expression reached a maximal level in 7-8 hr, at which time a significant
      increase in the tyrosine phosphorylation of multiple cellular proteins was
      detected, suggesting that the enhanced tyrosine phosphorylation of cellular
      proteins may result from activation of Fas-mediated death signaling. However,
      these aburatubolactam C-induced cellular changes and accompanied apoptosis were
      completely blocked in the presence of genistein, a known protein tyrosine kinase
      inhibitor. These results indicate that upregulation of FasL expression dictated
      by protein tyrosine kinase activation and subsequent mediation of Fas death
      signaling account for aburatubolactam C-induced apoptosis in Jurkat T cells.

PMID- 9600107
TI  - Separation of IRS-1 and PI3-kinase from GLUT4 vesicles in rat skeletal muscle.
AB  - In fat and muscle tissues, insulin stimulates cellular glucose uptake by
      initiating a phosphorylation cascade which ultimately results in the
      translocation of the GLUT4 glucose transporter isoform from an intracellular
      vesicular storage pool(s) to the plasma membrane in fat and to t-tubules in
      skeletal muscle. Insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3
      kinase (PI3-kinase) are known to be involved in cellular responses to insulin
      such as GLUT4 translocation, but the biochemical mechanism(s) connecting IRS-1
      and PI3-kinase to GLUT4-containing intracellular membranes remains unclear. Here,
      in control and insulin-stimulated rat skeletal muscle, the intracellular
      localization of these two proteins was compared to that of GLUT4 using
      subcellular fractionation by sucrose velocity gradients followed by
      immunoblotting. Our data show that insulin-sensitive GLUT4-containing vesicles
      are present in fractions 1 through 10, whereas IRS-1 and PI3-kinase are found in
      fractions 16 through 24. These results indicate that in intracellular fractions
      derived from skeletal muscle, IRS-1 and PI3-kinase are excluded from membranes
      harboring GLUT4.

PMID- 9600108
TI  - Transcriptional regulation of muscle-specific genes during myoblast
      differentiation.
AB  - A rapid, highly sensitive method to determine the mRNA level of muscle-specific
      markers using TaqMan PCR analysis was developed and used to study sequential gene
      regulation of myoblasts during induced differentiation of C2C12 cells. mRNA
      levels of muscle regulatory factor (MRF) myogenin, alpha-actin, thermoregulatory
      uncoupling protein UCP2 and glucose transporter isotype glut4 increased rapidly
      during early stage differentiation. In contrast, myf5, beta-actin, UCP1 and glut1
      mRNA levels gradually decreased during 8 days. However, the mRNA level of other
      genes such as MyoD, glyceraldehyde-3-phosphate dehydrogenase and hexokinase II
      changed only slightly in comparison. Muscle-specific uncoupling protein UCP3 mRNA
      was detected during differentiation and increased rapidly within 8 days. These
      data clearly show the sequential and the differential regulation of muscle
      specific genes in C2C12 cells during multinucleate myotube formation.

PMID- 9600109
TI  - The effects of iron and vitamin C co-supplementation on oxidative damage to DNA
      in healthy volunteers.
AB  - The effects of co-supplementing healthy volunteers with iron (14 mg/day ferrous
      sulphate) and vitamin C (either 60 mg/day or 260 mg/day as ascorbic acid) on
      levels of oxidative DNA damage in white blood cells were studied. The subjects
      were divided into two groups: one group of 20 volunteers with a higher mean
      initial level of plasma vitamin C (71.9 +/- 14.0 mumol/l) and a second group of
      18 volunteers with a lower mean level (50.4 +/- 25.8 mumol/l). In the first group
      there was a significant rise in several oxidative DNA base damage products and in
      total oxidative DNA damage in DNA extracted from white blood cells, but not in 8
      hydroxyguanine, after 6 weeks of supplementation. However, after 12 weeks levels
      returned approximately to normal. In the group with the lower initial level of
      plasma ascorbate, presupplemental levels of oxidative DNA damage were higher and
      decreased on supplementation with iron and ascorbate. Since oxidative DNA damage
      has been suggested as a risk factor for the development of cancer, the
      implications of increased levels in well-nourished subjects after iron/ascorbate
      supplementation are disturbing in view of the frequent use of dietary supplements
      containing both iron salts and ascorbate.

PMID- 9600110
TI  - Establishment of a novel human B-cell line (OZ) with t(14;18)(q32;q21) and
      aberrant p53 expression was associated with the homozygous deletions of p15INK4B
      and p16INK4A genes.
AB  - The novel human pre-B cell line OZ was established from a patient with an
      aggressive form of non-Hodgkin's lymphoma. Karyotypic analysis of both the
      primary tumour and OZ cells revealed several marker chromosomes, including the
      t(14;18)(q32;q21) translocation, which involves the Bcl-2 gene, and alterations
      on chromosome 17p. Southern blot analysis found identical rearrangements in the
      5' region of Bcl-2 gene in the primary tumour and OZ cells. Homozygous deletions
      of the p15INK4B and p16INK4A genes, however, were present only in OZ cells.
      Western blot analysis detected aberrant small molecular-weight p53 proteins in
      both cell types. In addition, OZ cells no longer expressed the CD20 antigen.
      These findings suggest that Bcl-2 gene rearrangement and aberrant p53 expression
      resulted in the original B-cell tumour. A subsequent transforming event involving
      the p15INK4B and p16INK4A genes may have generated more immature cells with a
      growth advantage during in vitro culture. The genetic alterations involving p53,
      p15INK4B, and p16INK4A may be implicated in the aggressive form of
      t(14;18)(q32;q21)-bearing tumours and their poor prognosis.

PMID- 9600111
TI  - Levels of proteins C and S do not decline subsequent to first line chemotherapy
      in lymphoma patients.
AB  - Thromboembolic complications and decrease in protein C and S have been observed
      in patients while receiving combination chemotherapy for breast cancer. We
      investigated whether initial cytotoxic treatment of non-Hodgkin's lymphoma (NHL)
      and Hodgkin's disease (HD) is also associated with changes in these anticoagulant
      parameters. For this purpose 25 patients with intermediate to high grade NHL and
      seven with HD, undergoing primary treatment with cytotoxic drugs were evaluated
      at three time-points: pre-therapy, mid-therapy and post-therapy. In contrast to
      the breast cancer patients, no significant changes in protein C, protein S and
      antithrombin III levels were observed in the NHL patients during the various
      stages of therapy. However in HD patients, the mean protein C values had a
      tendency to be higher at mid-therapy compared to pre-therapy and protein S levels
      had a tendency to be higher at mid-therapy compared to post-therapy. In lymphoma
      patients receiving primary cytotoxic treatment we did not find changes in
      anticoagulant parameters that can explain a chemotherapy-induced hypercoagulable
      state, as has been reported in breast cancer patients.

PMID- 9600112
TI  - Vaccination as immunotherapy for B cell lymphoma.
AB  - Current therapy does not cure the majority of patients with B cell non-Hodgkin's
      lymphoma (NHL) and further intensification does not benefit the patient.
      Therefore, new approaches are necessary. Immunotherapy has become again a major
      interest as a new treatment modality for B cell lymphoma since the discovery that
      the lymphoma specific Id can be presented to antigen-specific T cells.
      Vaccination of the tumour-bearing host is one of the major strategies to induce a
      T cell mediated anti-tumour immunity in vivo. For B cell lymphomas the lymphoma
      specific Id can be used as a tumour-specific antigen to stimulate T cells.
      Alternatively, the malignant B cells can be modified to become efficient antigen
      presenting cells (APCs) and present peptides from their own tumour-specific
      antigens to the autologous T cells. Currently explored and future vaccination
      strategies for B cell lymphoma will be discussed here.

PMID- 9600113
TI  - Clinical presentation, hematologic features and treatment outcome of childhood
      acute lymphoblastic leukemia: a review of 73 cases in Hong Kong.
AB  - Seventy-three consecutive cases of childhood acute lymphoblastic leukemia (ALL)
      diagnosed and managed in Queen Mary Hospital over a 10-year period from 1985 to
      1994 were retrospectively analysed for their presenting features and treatment
      outcome. The 48 boys and 25 girls ranged in age from 0.4 to 14.2 years (median:
      4.3 years). Bone and joint pain was a relatively common presenting feature
      besides fever, hepatosplenomegaly and lymphadenopathy. Immunophenotyping of blast
      cells showed: 51 B-cell precursor ALL, one B-ALL, 10 T-ALL and three myeloid
      antigen positive ALL. Eight cases were unclassified since immunophenotyping had
      not been performed. Out of the 73 patients, treatment outcome was analysed in 20
      cases treated with UKALL-VIII regimen and 28 cases treated with either the UKALL
      XI regimen or the Hong Kong Children Cancer Study Group (HKCCSG) protocol which
      was modelled upon UKALL-XI. Although complete remission rates were similar
      between the two groups, patients treated with the former regimen that was less
      intensified suffered more relapses than the latter (56 per cent versus 21 per
      cent, P = 0.04). There were, however, no significant differences both in event
      free survival (38.2 +/- 11.2 per cent versus 71.3 +/- 9.3 per cent, P = 0.12) and
      overall survival (70.0 +/- 10.2 per cent versus 79.6 +/- 8.3 per cent, P = 0.41)
      between the two groups at 3 years by long-rank test. With the use of risk
      directed therapy and improved supportive care, two-thirds of our patients are
      able to enjoy long-term event-free survival.

PMID- 9600114
TI  - 12-O-tetradecanoylphorbol-13-acetate (TPA) downregulates expression of CD30 in
      erythroleukemia cell line K562.
AB  - CD30, a member of the tumour necrosis factor/nerve growth factor receptor
      superfamily, has been thought to have pleiotropic functions on immune response.
      However, there has been only a little information about the mechanism of CD30
      expression. In this study, modulation of the CD30 molecule was investigated by
      the treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). When cultures
      were supplemented with TPA, CD30 transcript was downregulated in a dose- and time
      dependent manner in the erythroleukemia cell line K562. Half reduction of CD30
      transcript, precursor protein and surface protein was at 3 h, 6 h, and 40 h,
      respectively, by Northern blot and Western blot analyses. This consecutive
      reduction of both the transcript and proteins suggests that TPA directly inhibits
      the transcriptional step of CD30, and subsequently CD30 molecules would decrease
      on the cell surface. To determine whether the protein kinase C (PKC) pathway is
      involved in this reduction, a PKC inhibitor, 10 microM H-7, was added to the K562
      culture. The addition of H-7 recovered the inhibitory effect of TPA, indicating
      that PKC is involved in the transcription of CD30. When either 2 micrograms/ml
      actinomycin D or 20 micrograms/ml cycloheximide was added simultaneously with TPA
      to the culture, the repressive effect of TPA on CD30 was abolished. These results
      showed that the repression would also partly involve ongoing mRNA and protein
      synthesis under TPA treatment.

PMID- 9600115
TI  - The role of Epstein Barr virus (EBV) in Burkitt's lymphomas.

PMID- 9600116
TI  - Monitoring of solar-UV exposure among schoolchildren in five Japanese cities
      using spore dosimeter and UV-coloring labels.
AB  - To monitor personal exposure to biologically effective solar-UV radiation,
      Bacillus subtilis spores on a membrane filter and UV-coloring labels were
      incorporated into a monitoring badge. The samples were covered with one of three
      types of filter sheet, dependent on the season, to reduce the amounts of exposure
      to measurable levels. Five fifth- or sixth-grade classes of primary schools, each
      consisting of 30-40 children, were chosen in northern (Sapporo), central (Tsukuba
      and Tokyo), and southern (Miyazaki and Naha) cities in Japan. In all four season,
      each child wore a badge on an upper arm for the entire waking hours, changing it
      daily, for a week. Upon collection of the badges, the survival of spores and the
      extent of coloration of the label were determined. The results were used to
      estimate the amount of daily exposure to biologically effective UV radiation,
      expressed as the value of spore inactivation dose. Unexpectedly, the average
      amounts of exposure were not directly correlated with the outdoor UV irradiance:
      in the two southern cities, despite high outdoor irradiance from spring to
      autumn, the average amounts of exposure were less than 3.1% of the average
      irradiance. Highly concentrated exposures occurred in two central cities on three
      days when extensive outdoor exercise took place. These results contradict the
      simple notion that children's exposure is in proportion to the outdoor UV
      irradiance, and support the view that the extent of solar-UV exposure is
      primarily determined by life-style rather than living location.

PMID- 9600117
TI  - Anthropometric and other risk factors for ovarian cancer in a case-control study.
AB  - Because it has been suggested that an environmental factor may play a role in the
      etiology of ovarian cancer, a case-control study was conducted to assess some
      environmental and other risk factors for ovarian cancer from 1994 to 1996 in
      northern Kyushu, Japan. We analyzed the data of 89 cases with epithelial ovarian
      cancer and 323 controls without any cancer or ovarian disorder. After controlling
      for the effect of potential confounders, the odds ratios of ovarian cancer across
      increasing quartiles of the heaviest body weight were 1.00, 1.15, 1.71, 2.29 (P =
      0.008, test for trend). Significantly increased risks were noted for a history of
      diabetes mellitus (P < 0.05), and for a family history of ovarian cancer (P <
      0.05). Significantly decreased trends for risk were obtained for the number of
      pregnancies (P < 0.01) and the number of live births (P < 0.001). This study
      provides additional support for an association between obesity and the risk of
      ovarian cancer. This relationship may at least partly explain the recent increase
      in the incidence of ovarian cancer in Japan, although possible contributions of
      other factors can not be ruled out.

PMID- 9600118
TI  - Influence of drinking green tea on breast cancer malignancy among Japanese
      patients.
AB  - Inhibitory effects of green tea on carcinogenesis have been investigated in
      numerous laboratory studies using (-)-epigallocatechin gallate (EGCG) or crude
      green tea extract, and there is also some epidemiologic evidence. Further, EGCG
      has been reported to inhibit the growth of cancer cells, lung metastasis in an
      animal model, and urokinase activity. In this study, we first examined the
      association between consumption of green tea prior to clinical cancer onset and
      various clinical parameters assessed at surgery among 472 patients with stage I,
      II, and III breast cancer. We found that increased consumption of green tea was
      closely associated with decreased numbers of axillary lymph node metastases among
      premenopausal patients with stage I and II breast cancer and with increased
      expression of progesterone receptor (PgR) and estrogen receptor (ER) among
      postmenopausal ones. Since these are potential prognostic factors, we then
      investigated the prognosis of breast cancer with special reference to consumption
      of green tea, in a follow-up study of these patients. We found that increased
      consumption of green tea was correlated with decreased recurrence of stage I and
      II breast cancer (P < 0.05 for crude disease-free survival); the recurrence rate
      was 16.7 or 24.3% among those consuming > or = 5 cups or < or = 4 cups per day,
      respectively, in a seven-year follow-up of stage I and II breast cancer, and the
      relative risk of recurrence was 0.564 (95% confidence interval, 0.350-0.911)
      after adjustment for other lifestyle factors. However, no improvement in
      prognosis was observed in stage III breast cancer. Our results indicate that
      increased consumption of green tea prior to clinical cancer onset is
      significantly associated with improved prognosis of stage I and II breast cancer,
      and this association may be related to a modifying effect of green tea on the
      clinical characteristics of the cancer.

PMID- 9600119
TI  - Establishment of Epstein-Barr virus-positive human gastric epithelial cell lines.
AB  - We have established two Epstein-Barr virus (EBV)-positive cell lines, GT38 and
      GT39, derived from human gastric tissues of two patients bearing gastric
      carcinoma. Both cell lines were positive for cytokeratin, an epithelial marker,
      but not for lymphocyte-related markers. Unlike GT39 cell line, GT38 cells lacked
      the property of contact inhibition. EBV genome was detected in both cell lines.
      The cell lines were positive for latent membrane protein 1, and EBV-determined
      nuclear antigen 1 (EBNA1). EBNA2 was also detected in GT38. These cell lines
      should be useful for studying the interaction of EBV with gastric epithelial
      cells and its role in gastric carcinogenesis.

PMID- 9600120
TI  - p53 gene mutation and loss of heterozygosity of chromosome 11 in
      methylcholanthrene-induced mouse sarcomas.
AB  - Mutations of the p53 tumor suppressor gene are the most prevalent genetic
      alteration observed in a wide variety of human cancers. In this study we examined
      63 methylcholanthrene (MCA)-induced sarcomas from C57BL/6N x C3H/HeN F1 (BCF1) or
      C3H/HeN x C57BL/6N F1 (CBF1) mice for p53 gene mutations and loss of
      heterozygosity (LOH) of chromosome 11. Mutation analysis was done on exons 5 to 8
      of the p53 gene by polymerase chain reaction-single strand conformation
      polymorphism analysis. This identified 53 potential mutations in 45 sarcomas.
      Mutations were further confirmed by direct sequencing of the region. Forty-nine
      of the 53 cases (94%) were missense mutations, while the rest included two
      nonsense mutations, one silent mutation and one insertional mutation. Spectra of
      base substitutions were: 25 cases (47%) of G:C-->T:A transversion, 13 cases (25%)
      of G:C-->A:T transition (CpG site 15%), 13 cases (24%) of G:C-->C:G transversion,
      a case (2%) of A:T-->T:A transversion and a case (2%) of insertion. In addition,
      analysis of 5 polymorphic markers of mouse chromosome 11 revealed LOH in ten
      cases (22%) among those carrying p53 mutations. In nine of these 10 cases, the
      loss involved all 5 markers. In addition, the loss was biased toward the C57BL
      allele (9 cases). The present study establishes the pattern of mutation of the
      p53 gene in MCA-induced mouse sarcomas.

PMID- 9600121
TI  - Loss of pS2 protein expression is an early event of intestinal-type gastric
      cancer.
AB  - To investigate the prevalence of pS2 expression in gastric cancer with respect to
      tumor histopathology, intestinal metaplasia and Helicobacter pylori (H. pylori)
      infection, pathologic specimens of 91 patients with gastric cancer were
      immunostained for pS2. Such immunoreactivity was correlated with the status of H.
      pylori infection, tumor staging, histology, subtyping, and associated intestinal
      metaplasia. Positive pS2 staining was seen throughout all non-neoplastic
      epithelia, and in all 9 patients with the complete type of intestinal metaplasia.
      In contrast, 21 of 45 incomplete type of intestinal metaplasia had negative pS2
      staining (P < 0.001), and 54 out of 91 tumors (59.3%) showed loss of pS2
      expression in the cancer tissues proper. There was no correlation of pS2
      expression with age, gender, depth of invasion, duodenal involvement, lymph node
      metastasis, venous invasion or H. pylori infection. Negative pS2 staining was
      significantly higher in the intestinal (74.5%) and Borrmann type I, II, III
      (64.2%) tumors than the diffuse (43.2%, P < 0.005) and Borrmann type IV (20%, P <
      0.05) tumors. Our results indicate that loss of pS2 expression may occur as an
      early event in the malignant transformation process of intestinal-type tumors.

PMID- 9600122
TI  - CD44 variant isoform expression and breast cancer prognosis.
AB  - We examined the expression of CD44 isoforms in samples of breast cancer tissues
      from 95 patients by reverse transcription-polymerase chain reaction and
      immunohistochemistry, and tried to correlate the results with survival period. At
      the RNA level, expression of exon v2 was observed in 33 (35%) and that of v6 in
      69 (73%) of the 95 specimens. Patients with CD44v2 mRNA expression had
      significantly shorter survival times than those with v2-negative tumors (P =
      0.05), but there was only a weak correlation, if any, between v6 mRNA expression
      and overall survival (P = 0.06). Tumor tissue from 22 (23%) and 72 (76%) patients
      showed positive immunoreactivity with monoclonal antibody (mAb) M23.6.1. (CD44v2)
      and mAb 2F10 (CD44v6), respectively. Immunohistochemical evidence of CD44v2
      peptide expression correlated with overall survival (P = 0.02), but there was no
      such association with CD44v6 expression in these tumors (P = 0.67). There were
      significant correlations between v2 immunoreactivity and higher histological
      grade and lower levels of estrogen and progesterone receptor. There was no
      significant correlation between v6 immunoreactivity and such clinicopathological
      characteristics. Although the expression of v2 was significantly associated with
      reduced overall survival, it was not an independent prognostic factor because it
      also correlated with progesterone receptor status. These findings suggest that v2
      isoform expression might have more value than v6 expression for clinical use.

PMID- 9600123
TI  - Up-regulation of CD44 variant exon expression in endometrial carcinomas: analysis
      of mRNA and protein isoforms, and relation to clinicopathological factors.
AB  - In order to clarify the relation between expression of individual CD44 variant
      exons and tumor progression, 34 endometrial carcinomas (endometrioid type) were
      investigated, as well as 27 samples of normal endometrium, using a combination of
      reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot
      hybridization (SBH). Western blotting was also performed for comparison of
      protein levels with the results of the RT-PCR/SBH methods. Analysis of gross CD44
      splicing patterns demonstrated high-level expression of variant isoforms in
      endometrial carcinomas as compared with normal endometrium. Exon-specific RT
      PCR/SBH assays revealed large, abundant transcripts of individual variant exons
      in particular v3, v4, and v5, in tumors, but these isoforms were also expressed
      in normal endometria, suggesting a lack of tumor-specificity. No individual CD44
      variant transcripts were associated with any of the prognostic factors
      investigated. Parallel observations showed variant CD44 transcripts to be more
      readily detectable than protein isoforms in the same samples. These findings
      indicate that in endometrial carcinomas, expression of individual variant CD44
      exons is markedly up-regulated, but this molecule may not be useful as a
      consistent indicator of tumor progression.

PMID- 9600124
TI  - Genetic alterations of mixed hyperplastic adenomatous polyps in the colon and
      rectum.
AB  - Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or
      even carcinomas. These polyps are considered to be different from ordinary
      hyperplastic polyps and may have a preneoplastic potential. We investigated APC
      and K-ras mutations in MHAPs of the colon and rectum, and also in colorectal
      adenomas and hyperplastic polyps to identify molecular differences between MHAPs,
      adenomas and hyperplastic polyps, using direct sequencing of mutation cluster
      regions (MCR) in APC and K-ras. No APC mutations were identified in 12 MHAPs and
      8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic
      mutations. K-ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8
      (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was
      found in a carcinoma arising in an MHAP. Mutations other than APC mutations may
      play a role in the development of MHAPs.

PMID- 9600125
TI  - Early phase tumor accumulation of macromolecules: a great difference in clearance
      rate between tumor and normal tissues.
AB  - The objective of this study was to investigate the molecular weight (MW) and time
      dependence of the phenomenon termed "the enhanced permeability and retention"
      (EPR) effect in solid tumor, in particular to determine and define the early
      phase accumulation of macromolecules in tumor and normal tissues and the
      relationship between blood concentration and tissue clearance. As a model,
      radioiodinated N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers of MW ranging
      from 4.5 K to 800 K were administered i.v. to mice bearing sarcoma 180 tumor.
      Within 10 min all HPMA copolymers accumulated effectively in the tumor regardless
      of MW (1.0-1.5% of injected dose per g of tumor). However, higher MW copolymers
      (> 50 K) showed significantly increased tumor accumulation after 6 h, while the
      lower MW copolymers (< 40 K) were cleared rapidly from tumor tissue due to rapid
      diffusion back into the bloodstream. Blood clearance was also MW-dependent; the
      lower MW copolymers displayed rapid clearance, with kidney radioactivity of the
      copolymers of MW < 20 K representing 24% of injected dose per g kidney at 1 min
      after i.v. administration. Within 10 min these copolymers passed through the
      kidney and were excreted in the urine. Higher MW copolymers consistently showed
      kidney levels of 3-5% dose per g kidney in the early phase with no time-dependent
      accumulation in kidney. There was also no progressive accumulation in muscle or
      liver, regardless of polymer MW. These results suggest the "EPR effect" in solid
      tumor primarily arises from in the difference in clearance rate between the solid
      tumor and the normal tissues after initial penetration of the polymers into these
      tissues.

PMID- 9600126
TI  - Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in
      small cell lung carcinoma cells.
AB  - Previously, we demonstrated that inostamycin, an inhibitor of
      phosphatidylinositol turnover, caused cell cycle arrest at the G1 phase,
      inhibiting the expression of cyclins D1 and E in normal cells. In the present
      study, we examined the effects of inostamycin on cell cycle progression and
      apoptosis in human small cell lung carcinoma Ms-1 cells. Treatment of
      exponentially proliferating Ms-1 cells with low concentrations of inostamycin
      caused cells to accumulate in the G1 phase. We found that inostamycin decreased
      cyclin D1, and increased cyclin-dependent kinase inhibitors such as p21WAF1 and
      p27KIP1 in Ms-1 cells. On the other hand, higher concentrations of inostamycin
      induced morphological apoptosis and DNA fragmentation in Ms-1 cells without
      affecting the expression of p53, Bcl-2 and Bax. Inostamycin-induced apoptosis was
      suppressed by an inhibitor of caspase-3, and a 17 kDa fragment of activated
      caspase-3 was detected following inostamycin treatment. Therefore, caspase-3(
      like) would appear to be involved in inostamycin-induced apoptosis. On the other
      hand, an inhibitor of caspase-3(-like) proteases did not affect the inhibitory
      effect of inostamycin on cyclin D1 expression, suggesting that caspase-3(-like)
      proteases were not responsible for inostamycin-induced G1 arrest.

PMID- 9600127
TI  - Increased sensitivity to long-term 5-fluorouracil exposure of human colon cancer
      HT-29 cells resistant to short-term exposure.
AB  - A 5-fluorouracil (5-FU)-resistant subline of human colon cancer HT-29 cells was
      developed by repeated 1-h exposure in vitro to 5-FU. This subline (HT-29/5-FU/S)
      had 8-fold resistance to 5-FU in a 1-h exposure assay. However, it had rather
      increased sensitivity to 5-FU when assayed after a continuous 96-h exposure to
      it. Significantly less 5-fluorouridine-5'-triphosphate was produced in the
      resistant cells, leading to a lower level of 5-FU incorporation into the cellular
      RNA. The reduced activity of orotate phosphoribosyltransferase might explain
      these results. In contrast, the HT-29/5-FU/S cells were more sensitive to the
      inhibition of in situ thymidylate synthase (TS) by 5-FU than were the parent
      cells. The lower in situ TS activity may have made HT-29/5-FU/S cells more
      sensitive to TS inhibition by 5-FU as compared with the parent cells. The fact
      that HT-29/5-FU/S was more resistant to short-term 5-FU exposure but more
      sensitive to long-term exposure than the parent line confirmed the existence of
      different modes of action of 5-FU, depending on the exposure time.

PMID- 9600128
TI  - Intrinsic sensitivity of tumor cells to bleomycin as an indicator of tumor
      response to electrochemotherapy.
AB  - Electrochemotherapy (ECT) involves the use of locally applied electric pulses to
      increase delivery of chemotherapeutic drugs into cells in tissues. ECT with
      bleomycin (BLM) is a very effective local treatment, but different tumors have
      different response rates to ECT. The aim of our study was to compare the
      responsiveness of SA-1 and EAT tumors to BLM and ECT in vitro and in vivo, in
      order to find possible reasons for the observed difference in response rate. The
      difference in sensitivity to ECT in vitro between the SA-1 and EAT cells was 10
      fold and was the same as the difference in sensitivity to chronic BLM exposure,
      as measured by tetrazolium-based colorimetric (MTT) assay. This difference in
      sensitivity between SA-1 and EAT to ECT was also reflected in tumor cure rate. A
      six-times lower dose of BLM was needed to obtain local tumor control in SA-1 than
      in EAT tumors. Therefore, we suggest that the difference in sensitivity to BLM
      and ECT predominantly reflects the difference in intrinsic sensitivity of the
      cells to BLM.

PMID- 9600129
TI  - Effects of boron neutron capture therapy using borocaptate sodium in combination
      with a tumor-selective vasoactive agent in mice.
AB  - Boron neutron capture therapy (BNCT) destroys tumor cells by means of alpha
      particles and recoil protons emitted by 10B(n, alpha)7Li reaction. For BNCT to be
      effective, the tumor/normal tissue concentration ratio of 10B must be larger than
      1.0, because neutron distribution is not selective. We examined the combination
      of 10B-enriched borocaptate sodium (BSH) with flavone acetic acid (FAA) as a
      model compound which causes vascular collapse in squamous cell carcinoma in mice
      (SCCVII tumors) and would increase the tumor/normal tissue concentration ratio of
      10B. FAA (200 mg/kg, i.p.) was injected, and 5 min later BSH (75 mg/kg, i.v.) was
      administered, followed 15 to 180 min later by irradiation with thermal neutrons.
      The 10B concentrations were measured by prompt gamma ray spectrometry. Without
      FAA, tumor 10B concentrations were less than or equal to normal tissue
      concentrations at all time intervals, except that the concentrations were 1.7- to
      2.7-fold greater in tumor than muscle at 15 and 180 min after injection of BSH.
      With FAA, 10B concentrations 2.1- to 6.9-fold greater in tumor than in muscle
      were achieved at all intervals tested. For blood and skin, significant
      differential accumulations were found in tumors at 120 and 180 min. Tumor/liver
      ratios were less than 1 at all times. Cell survival was determined by in vivo/in
      vitro colony assay, and increasing radiosensitization correlated with increasing
      tumor 10B concentrations, whether or not they were achieved with FAA. Tumor
      control rates, determined at 180 days after BNCT, similarly appeared to depend
      only on 10B levels at the time of irradiation. Because 10B levels correlate with
      the radiation response of tissues, a therapeutic gain would be expected whenever
      the tumor levels exceed normal tissue levels, such as in tumors located in muscle
      irradiated at 15-180 min after FAA + BSH, or in those in skin irradiated at 120
      and 180 min.

PMID- 9600130
TI  - Patients' views on residual blood use for research purposes.
AB  - In order to document patients' views on residual blood use for research purposes,
      a questionnaire survey was conducted at Aichi Cancer Center Hospital in October
      1997. Subjects were patients who had undergone blood tests at a central blood
      sampling room in the morning during the week of the study enrollment. The
      questionnaire was handed out and collected at a waiting area in front of the
      blood sampling room. Of the 583 patients to whom we tried to hand out the
      questionnaire, 558 participated (258 males, 294 females, and 6 of sex unknown)
      and 25 refused. Those who regarded research to improve health care as important
      were 76.7% of those sampled. Only 28 patients (5.0%) answered that they would not
      permit the use of their residual blood for research purposes. Although logistic
      analysis did not detect significant factors influencing the giving of permission,
      the percentage who would not permit the use of their residual blood for research
      purposes was significantly higher in cancer outpatients (6.7%) than in inpatients
      (1.0%). It seems desirable for hospitals to establish an open policy concerning
      residual blood use for research purposes.

PMID- 9600131
TI  - [Urinary incontinence in patients in long-term institutional care. Results of an
      international study in 8 countries].
AB  - BACKGROUND: Urinary incontinence (UI) represents a prevalent nursing problem in
      geriatric facilities. Yet, comparison of the Czech Republic with countries using
      different chronic care system has not been conducted. METHODS AND RESULTS: Data
      from INTERRAI international database from 8 countries: Czech Republic, Denmark,
      France, Iceland, Italy, Japan, Sweden and USA have been evaluated in the sample
      of 280,271 nursing home residents. Prevalence of bladder and bowel incontinence
      and correlates with selected clinical factors have been determined and national
      samples compared with the results of 1080 patients in the Czech Republic.
      Prevalence of UI reached from 42.9% in Japan to 65.2% in France. France and CR
      belong to countries with the highest prevalence of both bladder and bowel
      incontinence. Cognitive impairment and dependency in ambulation are factors
      significantly associated with UI in all countries (p < 0.001). Immobility, age,
      gender and urinary tract infection reached the statistical significance only in
      some countries. CONCLUSIONS: High prevalence of bladder and bowel incontinence
      has been demonstrated in an extended sample of nursing home residents. Common
      protocol Resident Assessment Instrument-Minimum Data Set (RAI-MDS) and creation
      of a large cross-national database are opening up possibilities for a new level
      of clinical research in geriatrics.

PMID- 9600133
TI  - [Urinary stress incontinence in women and its conservative therapy].
AB  - Urinary incontinence is the most frequent symptom of impaired function of the
      lower urinary pathways. The most frequent cause of the development of stress
      incontinence is damage of the muscular pelvic floor and associated damage of the
      continent mechanism. In addition to surgical procedures there exist also various
      types of conservative treatment. The author submit different types of this
      treatment and the protocol used in his department.

PMID- 9600132
TI  - [Uro-gynecologic disorders in female geriatric patients].
AB  - As geriatric patients those above 60 years of age are described. Incontinence is
      not necessarily an associated symptom of old age. In women above 60 years 15-30%
      suffer from urinary incontinence. With advancing age the prevalence rises to more
      than 40%. The cause of miction trouble must not be sought only in the urogenital
      tract, where with advancing age under the influence of atrophic processes typical
      functional and anatomical changes take place, but also in the sphere of the CNS
      where in geriatric patients may be the cause of impaired continence. A
      preliminary classification of urinary incontinence may be made already on the
      basis of a detailed case-history. Data provided by the patient are usually not
      sufficient and it is necessary to obtain the required information on the
      character of incontinence by aimed questions. Furthermore it is of interest what
      sort of medication the patient is taking at the time, incl. medication she take
      spontaneously. Sometimes after mere discontinuation of certain drug groups
      complaints can be markedly reduced or completely eliminated. In the case-history
      we must always focus attention on risk factors associated with incontinence and
      questions on the abuse of alcohol are also justified. Somatic examination
      comprises gynaecological examination for evaluation of the anatomical
      characteristics at rest and during elevated intraabdominal pressure. Functional
      geriatric examination is the starting point for optimal care of old people. There
      is a number of functional geriatric tests. For clinical practice due to its
      straightforward character Barthel's test of basic everyday activities is useful.
      Urodynamic examination is not essential in geriatric patients. Information
      obtained in diagnostic processes may serve as a basis for rational therapy of
      incontinence. Different urodynamic methods are used in case therapy fails or when
      the anamnestic data are obscure.

PMID- 9600134
TI  - [When is surgery indicated for treatment of urinary stress incontinence?].
AB  - Stress incontinence is the most frequent type of urinary incontinence in women.
      Its diagnosis and therapy is a so far not quite resolved problem. In particular
      conservative treatment and the decision-taking algorithm leading, after
      conservative treatment has failed, to selection of a suitable operation has
      undergone changes during the past 10 years. Classification of different risk
      groups of patients, the decision-taking algorithm, the most frequent mistakes and
      errors during conservative treatment, indication and implementation of surgery
      incl. the most frequent complications are the subject of the submitted paper.

PMID- 9600135
TI  - [Inflammations of the lower urinary tract in women and possible treatment].
AB  - The rate of inflammations of the lower urinary pathways increases with advancing
      age. The development of inflammations depends not only on the presence of
      bacteria in the urinary pathways but also on various promoting factors. The most
      important and most frequent ones are obstructions of the urinary pathways with
      subsequent slowing down of the urinary flow or stasis. The microbe must adhere to
      the surface of the urothelium. The authors describes the specific adhesion of the
      most frequent agent Escherichia coli. On the surface of the bacteria are
      genetically defined fimbrias which react with receptors of the host cell. E. coli
      which have an affinity for the renal urothelium and cause pyelonephritis
      (fimbrias type P) differ from E. coli causing cystitis. The author indicates
      therapeutic approaches in complicated and non-complicated inflammations. "Single
      dose" treatment. Uroinfection during pregnancy. Uroinfection during
      postmenopause.

PMID- 9600136
TI  - [Urinary and fecal incontinence in geriatric facilities in the Czech Republic].
AB  - BACKGROUND: Incontinence represents one of the common problems in long-term care
      geriatric facilities and nursing homes. However, in the Czech Republic data on
      prevalence, severity and incontinence-associated factors for nursing home
      residents are not available. The aim of the study was to report the prevalence of
      urinary (UI) and bowel incontinence (BI) in different geriatric facilities and to
      identify factors positively associated with incontinence. METHODS AND RESULTS: In
      a sample of 1162 residents of 18 long-term care facilities UI has been found in
      684 residents (63.3%). Health and social care facilities did not differ
      significantly (60.7 vs 65.6%). Of the incontinent 294 residents (27.2%) suffered
      from permanent/daily incontinence, 390 (36.1%) from occasional transitory UI.
      Prevalence of BI reached 54.4%, as well as double incontinence (45.9%). Cognitive
      impairment, self-care ADL and/or mobility dependency and bed rest are factors
      significantly associated with UI (for all P < 0.001). However, age, gender and
      urinary tract infection did not reach the statistical significance (P = 0.280
      0.069). Risk adjustment/stratification for UI revealed the prevalence of 33.0% in
      the low risk group. In the high risk group (high ADL dependency and severe
      cognitive impairment) the prevalence came up to 96.0%. CONCLUSIONS: Our study
      presents the first results focused on incontinence problem in long-term care
      geriatric institutions in the Czech Republic. High prevalence of this condition
      makes incontinence an important medical, nursing and economical yet neglected
      problem.

PMID- 9600137
TI  - [Fluorides and bones].
AB  - Fluorides began to be used in the treatment of osteoporosis in the sixties when
      it was found that in areas with a high fluoride content of drinking water the
      prevalence of this disease is low. Fluorides stimulate osteoblasts to form more
      osteoid, and moreover larger crystals of bone mineral are formed which are more
      resistant to resorption by osteoclasts. Fluorides must be, however, administered
      always in combination with calcium and vitamin D. In the eighties a certain group
      of osteologists started a "campaign" against fluorides and maintained that after
      fluorides bone is of poor quality and there in a greater risk of fractures. All
      was explained by the fact that these authors administered fluorides alone in
      large doses. Recently with the introduction of monofluorophosphate into treatment
      instead of NaF there was a revival of fluorides which in combination with calcium
      and vitamin D are among the best stimulators of new formation of bone; after
      fluorides the bone density improves and they are used also in osteoporosis and
      preventively to avoid fractures.

PMID- 9600138
TI  - [Mercury in dental amalgams--a stress on the body or poisoning?].
AB  - The human organism is exposed to mercury from the environment and working
      environment. In the diet the main source of mercury are marine fish. Amalgam
      fillings participate in the mercury load of the organism as was proved by
      investigations of the mercury content of the brain, kidneys and lenses. However,
      it was not confirmed that the mercury load from amalgam fillings caused
      intoxication.

PMID- 9600139
TI  - [Biochemical markers of bone remodeling in assessment of osteoporosis].
AB  - The diagnostic significance of biochemical markers of bone remodelling is limited
      and it should always be evaluated together with results of other methods. Unlike
      bone densitometry, biochemical markers do not reflect bone mass and cannot be
      therefore used in diagnosis of osteoporosis. Markers enable for differential
      diagnostics of metabolic and neoplastic bone diseases and can be used for
      assessment of activity of bone disease and its monitoring. Different markers
      reflect aspects of bone remodelling. The sensitivity and specificity of the
      markers differ according to the type of bone disease and its treatment. The
      application of markers in monitoring treatment in individual patients requires an
      acceptable long-term biological variability of the marker (C.V. < 12%). In
      postmenopausal osteoporosis, osteocalcin measurements suffice in assessment of
      activity of the disease and for monitoring treatment. Lack of improvement in the
      marker can indicate poor compliance of the patient, a diagnostic error or an and
      organ resistance to treatment. The biochemical measurement predicts changes in
      bone mass about one year prior to bone densitometry, thus enabling for decision
      concerning urgency of therapeutic intervention. In individual patients, however,
      a single measurement of a biochemical marker cannot be used to predict long-term
      changes in bone mass. Osteokalcin is cleared from the circulation by kidney and
      cannot be used to assess bone remodelling in chronic renal failure patients. This
      is not true with bone-specific alkaline or acid phosphatase isoenzymes. Low serum
      osteocalcin concentrations have special significance in hypercortisolism.
      Considering their high cost, the markers should be clinically applied under
      specified indications and only when standardised.

PMID- 9600140
TI  - Alcohol action on liver: dose dependence and morpho-biochemical correlations.
AB  - BACKGROUND: Since the duration and the dose of alcohol administration are
      acknowledged as factors that influence the risk of liver injury, it was
      interesting to compare the character and degree of liver damage following various
      doses and methods of alcohol administration. In addition, it was assumed to
      compare the degree of liver damage histologically and on the activity of marker
      liver enzymes in blood plasma in the same animals. METHODS AND RESULTS: The
      several experiments on heterogeneous stock rats with the various daily dose,
      duration and method of alcohol administration have been carried out. It was
      found, that the 9-month intake of 15.20% (v/v) ethanol solution as the only
      source of drinking (the consumption of absolute alcohol was about 4 g/kg/day) did
      not affect the normal development of animals and did not induce any harmful
      morphological changes in liver. Moreover, the liver parenchyma looks even better
      in the context of lesser inflammatory infiltration and vacuolisation of
      hypatocytes. The activities of the marker liver injury enzymes: alanine and
      aspartate amino transferases (ALT and AST), alkaline phosphatase (AP) as well as
      alcohol dehydrogenase (ADH) in blood were also not changed. The intragastric
      administration 25% (v/v) ethanol (3.5 g/kg twice a day, during 14 days) induced
      some morphological disturbances in the liver: an extension of blood capillaries
      and veins in parenchyma and insignificant increasing of the hepatocyte
      vacuolisation degree (from 0.7 +/- 0.1 points in control to 1.2 +/- 0.2 points in
      alcohol treated animals). In blood serum, a slight elevation of ADH (from 1.2 +/-
      0.2 microM/min/l in control to 1.7 +/- 0.3) and AP (from 236 +/- 19 microM/min/l
      in control to 278 +/- 25) activities were found. The liquid alcohol diets (mean
      consumption of absolute alcohol was 14-18 g/kg/day, during a month) induced the
      more pronounced liver injury: extension of the liver blood vessels, inflammatory
      infiltration (from 1.1 +/- 0.1 points in control to 2.0 +/- 0.3; P, 0.05) and
      destruction of hepatocytes (from 0.5 +/- 0.01 points in control to 1.2 +/- 0.1; p
      < 0.05). Another liquid alcohol diet (mean consumption of absolute alcohol was 20
      24 g/kg/day, during a month) induced the expressive hepatocyte vacuolisation
      (from 0.5 +/- 0.1 points in control to 1.5 +/- 0.2; p < 0.05). In both the
      experiments, the weaker staining of hepatocyte cytoplasms, basophilia in
      particular, were found. The activity of blood plasma ADH was insignificantly
      increased by 47% and 134% and that of AP--by 15% and 38%. The activity of ALT
      insignificantly increased in the third experiment only and AST remained
      unchanged. Some correlations among the morphological and biochemical indexes were
      found in the above experiments: between the degree of hepatocytes vacuolisation
      and the blood ADH or AP activities (r = 0.62; p < 0.01 and r = 0.54; p < 0.05),
      accordingly. The oxyphilia intensity correlated with the AST activity (r = 0.64;
      p < 0.01) and the intensity of hepatocyte basophilia with the ADH activity (r =
      0.67; p < 0.01). The negative correlation was also found between the degree of
      extension of liver blood vessels and the activity of AST (r = -0.57; p < 0.05).
      CONCLUSIONS: The data obtained confirm the earlier observations concerning the
      dependence of the degree of liver injury on the dose and manner of alcohol
      administration as well as great individuality in the liver response to alcohol in
      heterogeneous stock rats. There are the significant correlations between the some
      morphological and biochemical markers of alcohol liver injury; among the
      biochemical markers studied, the ADH activity was the most sensitive.

PMID- 9600141
TI  - [Chronic dyspepsia. Basic classification based on symptoms and relation to
      gastrointestinal intolerances and diseases].
AB  - BACKGROUND: For expedient examination and treatment of chronic dyspepsias initial
      classification into groups which do not overlap in the main signs is necessary.
      Such a classification is lacking. The authors used a classification according to
      bitter or solely acid regurgitations and vomiting and their absence and according
      to the frequency and occurrence of bowel movements in the course of the day.
      METHODS AND RESULTS: In a group of 366 subjects (92 men and 274 women) aged 19 to
      76 years (mean 52.3 years) readily available data were evaluated statistically
      (chi square and agreement of two relative frequencies): symptomatology, objective
      finding, gastrointestinal intolerance (IT). 116 statistically significant
      relationships were revealed and were divided into four groups: 1, group with
      bitter manifestations in the morning on fasting and during the night with a
      relation to milk IT (less with lactose IT) and postprandial diarrhoea. 2. group
      with bitter manifestations after a meal and in daytime, related to biliary
      disease and IT of fat. 3. group with solely acid manifestations associated with
      IT of vinegar, alcohol, gastroaggressive drugs and oligosaccharides and peptic
      ulceration also in remission. 4. group without regurgitations and vomiting which
      needed further classification: relatively tolerant of fat but not milk. This
      group has a characteristic sub-group of subjects with a quiescent stage after
      cholecystectomy. This sub-group is a "negative" of the properties of group 3.
      CONCLUSIONS: In the patients four defined groups of dyspepsias were defined
      associated with manifestations of actual intolerances of foods, savouries and
      drugs. Three of them are associated with antiperistaltic phenomena in the upper
      gastrointestinal tract.

PMID- 9600142
TI  - [Development of resistance and utilization of fluoroquinolones in a university
      hospital].
AB  - The results of a retrospective study in the Faculty Hospital, Hradec Kralove
      (FHHK) show a steep increase in the consumption of fluoroquinolones in the course
      of six years. Since 1989, when 360 defined daily doses (DDD) were administered,
      the consumption increased to 2,825 DDDs in 1992 and 52,162 DDDs in 1995. At the
      same time, resistance to ofloxacine and ciprofloxacine was increased many times
      in some bacterial species isolated from patients admitted to FHHK. In the strains
      Pseudomonas aeruginosa, resistance to ofloxacine increased from 3% to 38% in
      1995, in Serratia marcescens from 13% in 1992 to 30% in 1995. A marked increase
      was observed also in Acinetobacter calcoaceticus. In the naturally highly
      sensitive species E. coli and Klebsiella pneumoniae no increase in resistance has
      been observed yet, in Enterobacter cloaceae resistance slightly increased (from
      0% in 1992 to 7% in 1995). Due to the fact that in FHHK fluoroquinolones take the
      first place in the consumption of antibiotics at present, an increase in
      resistance can be expected also in these bacteria in the future. Investigation of
      changes in resistance due to the consumption of fluoro-quinolones is a suitable
      model of a pharmacoepidemiological study (DUE-Drug Utilisation Evaluation) as the
      relationship of the consumption of a drug and its effect can be observed
      practically since the introduction of fluoroquinolones into the market.

PMID- 9600143
TI  - [Analysis of the use of medicinal teas in relation to their effects].
AB  - The paper analyzes the consumption of mass-produced preparations of teas from the
      viewpoint of the sort and the group of indication. The packed plant drugs and
      teas were classified into the groups of indication according to Wichtl's
      pharmacodynamic system and the consumption was expressed in physical and
      financial indices. It follows from the results that mass-produced teas represent
      on average 6.6% of total sales of OTC drugs and supplementary assortment per
      month. The highest average monthly consumption was achieved by packed plant drugs
      and teas from group VI, miscellaneous teas for external and internal use, group
      I, diseases of the stomach and intestines, and group II, diseases of the
      respiratory tract.

PMID- 9600144
TI  - [Use of photoactivation in the preparation of radiopharmaceuticals. III. Human
      serum albumin labelled with technetium (99mTc)].
AB  - Human serum albumin was photoactivated by UV light at 254 nm and labelled with
      technetium(99mTc) by reducing pertechnetate(99mTc) with stannous chloride.
      Radiochemical purity was evaluated using paper chromatography, columns and
      electrophoresis. The biodistribution of labelled albumin in rats was determined
      by counting the activity in isolated organs 15 and 60 minutes after
      administration. Photoactivation raises the number of free SH groups, a fact
      exerting a beneficial effect on labelling efficacy. Irradiated albumin shows a
      higher labelling efficacy (99%) compared with non-irradiated albumin (96%).
      Structural changes depend on the dose of UV radiation, on the concentration of
      irradiated substance and on metal ion content (Sn2+). The results obtained
      suggest that the elimination, from blood, of albumin whose structure has been
      altered by photoactivation can be accelerated thereby creating the preconditions
      for its application in the diagnosis of inflammatory conditions.

PMID- 9600145
TI  - [Study of 2-(2-hydroxy-3-isopropylaminopropoxy)-5-(propoxymethyl) acetophenone--a
      potential adrenoreceptor beta blocker affecting the function of myocardial
      mitochondria after administration of isoprenaline].
AB  - The present paper evaluated the effect of the potential beta-adrenoreceptor
      blocker 2-(3-isopropylamino-2-hydroxypropoxy)-5-(propoxymethyl) acetophenone
      (FoA33) on the oxidative and phosphorylating processes of the cardiac muscle
      influenced by small doses of isoprenaline (2 mg.kg-1). Under selected
      experimental conditions, the consumption of oxygen by the mitochondria of the
      cardiac muscle in states S3 and S4, rate of production of energy by mitochondria
      (OPR), coefficient of oxidative phosphorylyzation (ADP:O), respiratory control
      index (RCI) as well as the effect on the specific activity of the
      cytochromoxidase marker of mitochondria (COX) were examined. It follows from the
      obtained results that in contrast to large doses of isoprenaline (10-50 mg.kg-1)
      producing necrosis and affecting metabolic processes, small doses of isoprenaline
      (2 mg.kg-1) in many parameters activate the bioenergetic activity of the cardiac
      mitochondria, which is only minimally changed in combination with the beta
      adrenoreceptor blocker (FoA33).

PMID- 9600146
TI  - [Phytotherapeutic aspects of diseases of the circulatory system. 6. Leuzea
      carthamoides (WILLD.) DC: the status of research and possible use of the taxon].
AB  - Leuzea carthamoides (WILLD.) DC., Asteraceae, has become an important taxon
      usable in human practice and animal production in recent years. Originally an
      endemic plant of southern Siberia, now it is widely grown not only in the Union
      of Independent States, once the original region of introduction, but also in
      central and eastern Europe. The principal constituents of the whole plant are
      ecdysteroids (5 beta-cholest-6-on-7-ene derivatives) and flavonoids. In addition,
      the aerial part contains sesquiterpenic lactones of the guajanolide type, and the
      roots contain polyines (on the thiophene base). The present paper comprehensively
      discusses the occurrence, content and biological activity of these substances,
      the preparations manufactured from the plant, their use in therapeutic practice,
      food manufacture and animal production in the world and the Czech Republic. The
      plant has certainly become a taxon with prospects in the Czech Republic,
      particularly as the source of 20-hydroxyecdysone, which is getting into the
      limelight in the world.

PMID- 9600149
TI  - [The present status and prospects of therapeutic use of beta-blockers in diseases
      of the cardiovascular system].
AB  - Beta-blockers are being revived as effective, safe, reasonably priced and well
      tolerated drugs. Differences in the pharmacodynamic and pharmacokinetic
      properties of beta-blockers now make it possible to select for the therapy of the
      individual diseases from a wide range of available beta-blockers the most
      effective drug with the minimal undesirable effects. It is made possible by the
      progress in the development of this ATS group and particularly by the third
      generation of these compounds. A proof of the prospects of these drugs is
      provided by their extended indications as the first-choice drugs (myocardial
      infarction) as well as the generally extended possibilities of their therapeutic
      use (therapy of heart failure).

PMID- 9600150
TI  - [Comparison of the reactivation effects of the HI-6 oxime and obidoximeon
      cyclosin-inhibited acetylcholinesterase in the diaphragm and various parts of the
      brain in rats].
AB  - In experiments on male rats the reactivating effects of oxime HI-6 and obidoxime
      in combination with atropine on acetylcholinesterase, inhibited by the highly
      toxic organophoshate cyclosin, were compared in various parts of the brain
      (frontal cortex, pontomedullar region, hypothalamus, hippocampus, basal ganglia)
      and the diaphragm. After intramuscular administration of cyclosine in a sublethal
      dose, a medium-serious inhibition of the diaphragmatic acetylcholinesterase and a
      various inhibition of this enzyme in the brain with the maximum in the frontal
      cortex took place in the first hours of intoxication. The subsequent antidotal
      therapy resulted in variously high reactivation of cyclosin-inhibited
      acetylcholinesterase in dependence on the selection of oxime. Practically in all
      regions under study, a significantly more marked reactivation of the given enzyme
      in the therapy of intoxication with oxime HI-6 was recorded. For the therapy of
      acute intoxications with highly toxic cyclosin, oxime HI-6 seems to be a more
      suitable reactivator of acetylcholinesterase than the hitherto used obidoxime.

PMID- 9600151
TI  - [Relation between smoking in reproductive-age women and disorders in
      reproduction].
AB  - In a retrospective anamnestic study a total of 3180 women teachers from primary
      schools in seven districts of the Czech Republic with a different incidence of
      statistically recorded reproductive disorders were examined. A professionally and
      socially homogeneous group was selected on purpose to standardize to a maximum
      extent exposure to detectable and undetectable risk factors and confounding
      factors in the working environment and living conditions. The respondents were
      classified according to their statements on smoking habits up to the age of 45
      years, which was taken as the reproductive period. Although the majority of
      smokers belonged into the group of mild smokers with a mean consumption of 10
      cigarettes per day, in this group significantly more frequent heavy menstrual
      bleeding, early and spontaneous abortions, deliveries of premature infants and
      infants born in term but with a low birthweight were recorded. Smokers had
      significantly more often induced abortions of unwanted pregnancies in the case
      history as compared with non-smokers. After elimination of women who by the time
      of the survey had never been pregnant yet, heavy smokers, as compared with non
      smokers had a more than twofold risk as regards difficulty to become pregnant, of
      spontaneous abortions, deliveries of premature infants: there was an almost
      double risk of delivery of a low birthweight infant even among medium heavy
      smokers.

PMID- 9600152
TI  - [Comparative study of three alternative surgical techniques for hysterectomy].
AB  - In conjunction with the introduction of laparoscopic hysterectomy into wider
      clinical practice significant changes take place in the evaluation of medical and
      economic aspects of alternate surgical techniques. In the investigated group the
      advantages of a minimally invasive and vaginal approach in the evaluation of
      perioperative parameters and time of convalescence were confirmed.
      Laparoscopically assisted vaginal hysterectomy by the simple coagulation
      technique reduces considerably the costs of the operation. Costs can be markedly
      cut by reducing the number of days in hospital and by an earlier return to work.
      After systemic problems associated with funding of the health services will be
      resolved it will be useful to implement further extensive prospective studies.
      The results of these studies along with medical findings can participate in a
      significant way to an optimal ratio of different alternate surgical techniques of
      hysterectomy.

PMID- 9600153
TI  - [Antibiotic prophylaxis of infectious complications in gynecologic surgery].
AB  - Infections are still the most frequent postoperative complications and one of the
      limiting factors of successful gynaecological surgery. In recent years
      information on successful anti-microbial chemoprophylaxis is increasing and is
      associated with reduced postoperative inflammations, febrile morbidity and early
      complications. Views differ above all as regards indications for the use of
      antibiotic prophylaxis and the selection of a suitable antibiotic. Data in the
      literature differ also as regards achieved results. The submitted work had the
      objective to test on a representative group the success and rationality of
      medicamentous prophylaxis in gynaecological surgery and to contribute to a
      clearer view on controversial points. 203 women admitted to the Second
      Gynaecological and Obstetric Department of the First Medical Faculty Charles
      University and General Faculty Hospital Prague for elective abdominal or vaginal
      hysterectomy on account of a benign indication were divided into three groups
      which did not differ from the demographic or medical aspect. In group A (53
      women) for prophylaxis two doses of Augmentin were used (combination of
      amoxycillin with clavulanic acid) i.v., patients in group M (50 women) had three
      doses of Mandol (Cefamandol) i.m., and in control group K (100 patients) no
      antibiotics were administered prophylactically. The authors investigated the
      postoperative course and evaluated some parameters in relation to possible
      postoperative infectious complications. The results proved unequivocally that
      prophylaxis with Augmentin reduces significantly the postoperative infectious
      morbidity (11.5%), febrile morbidity (5.6%) and the incidence of early infectious
      complications (3.8%) after abdominal or vaginal hysterectomy, as compared with
      the control group (35%, 31% and 11% resp.). Prophylaxis with Cefamandol reduced
      only in few parameters postoperative complications, but in general did not lead
      to a significant improvement of the postoperative course nor to a reduction of
      postoperative inflammatory complications. Similar results were obtained when only
      complications after abdominal hysterectomy were evaluated. The results of
      bacteriological examination confirmed the expected differences in the spectrum of
      efficacy of the two antibiotics on the most common microbial flora in the given
      area, i.e. a high sensitivity of Augmention to enterococci and bacterioids and
      resistance of these bacteria to Mandol. These results can be considered one of
      the reasons of different results of the two antibiotics. Prophylaxis with
      amoxycillin/clavulanic acid was found to be safe, very effective and financially
      feasible prevention of postoperative infectious complications after abdominal and
      vaginal hysterectomy. It led to a significant increase in the number of cases
      without any complications, when compared with the control group.

PMID- 9600154
TI  - [Treatment of early stages of ovarian carcinoma. Evaluation of experience at the
      Institute of Radiation Oncology over a 10-year period (1983-1993)].
AB  - The authors evaluated in a retrospective study the therapeutic results of ovarian
      carcinoma stage FIGO I (68 patients) and FIGO II (28 patients) attained in the
      Institute of Radiation Oncology, Prague during the ten-year period from 1983
      1993. Total survival and survival without relapse within five years are 77% in
      stage I and 74% in stage II. The corresponding values of five-year survival
      without relapse were 56% and 58% resp. Despite the fact that the therapeutic
      results are comparable with data in the literature, a great shortcoming is the
      inadequate documentation of the initial laparotomy and the very general
      histopathological finding, moreover without grading, in a great proportion of the
      patients. The authors emphasize that these shortcomings make a reliable
      indication of adjuvant therapy impossible, in particular in early stages of
      ovarian carcinoma. Despite repeated references to this shortcoming these mistakes
      have persisted for several decades.

PMID- 9600155
TI  - [Intracytoplasmic injections (ICSI) with epididymal and testicular spermatozoa].
AB  - Azoospermia is no longer a clear indication for using donor sperm. Aspiration of
      epididymal sperm or extraction of testicular sperm offers the same hope of
      pregnancy as ICSI using ejaculated sperm. Not even the high effectiveness of ICSI
      should be the reason for less intensive efforts to assess the exact cause of
      azoospermia, in particular with regard to genetic aspects.

PMID- 9600156
TI  - [Ethical and psychological problems of infertile couples in genetic counseling].
AB  - Study of attitudes and psychological opinions of infertile couples by anonymous
      questionnaires (answered separately by men and women), including 8 questions an
      supplement by 2 pages of explaining text. The questionnaires were sent to 140
      couples (280 persons), 37 couples answered (74 persons). The majority of these
      couples prefer assisted reproduction to adoption and they accept all varieties of
      these techniques. When donors are used, these couples wish to keep complete
      anonymity. They are prepared to pay for these procedures, even though they would
      prefer the opposite. The opinions of men and women did not differ greatly.
      However, the majority of men prefer choice of the baby's sex. This is not allowed
      in our and other European countries by law (with exception of families with X
      linked genetic diseases).

PMID- 9600157
TI  - [Sexual behavior in married women with chronic gynecologic inflammation].
AB  - Using an interview based on a uniform examination pattern comprising 70 items,
      the authors examined the sex life of 152 women aged 21-40 years, married for at
      least one year, treated at the time for chronic gynaecological inflammations in
      Frantiskovy Lazne. It was revealed that 55 probands (36.2%) did not report any
      marked changes in the course of sex life. 58 patients (38.2%) had unpleasant or
      painful sensations during coitus to which they responded in a rational way: by
      change or adjustment of the position, care taken by the partner, sometimes by
      discontinuation of coitus. The third sub-group was formed by 39 probands (25.6%)
      who were not satisfied with their sex life.

PMID- 9600158
TI  - [Contraceptive behavior in the population of the Czech Republic: results of a
      national survey].
AB  - Using an anonymous questionnaire the authors investigated in a representative
      group of the Czech population above 15 years of age (862 men and 857 women) the
      use of the main contraceptive methods. During the first intercourse more than
      half the respondents did not use any contraception, a condom was used only by 19%
      men and 14% women. In a steady partnership the most frequent method of
      contraception is coitus interruptus, whereby experience with hormonal
      contraception was reported by cca one third and with a condom by two thirds of
      respondents. Among younger men and women there are more users of hormonal
      contraception and condoms. Only 5% of the examined men and 4% of the women
      opposed any type of contraception, almost one quarter of respondents use only so
      called "natural methods" and almost three quarters of the respondents consider
      them an essential part of sex life. The attitudes of atheists and junior and more
      educated women are more liberal.

PMID- 9600159
TI  - [Is the anti-selection initiative in reproductive medicine anti-biological?].
AB  - The human reproduction has the monotocial element of K strategy (nidifungous)
      with mature newborn mammals and also of the r strategy (nidiculous) with immature
      mammals. There are questions about "contra naturam" antiselective practice in the
      treatment of extremely premature newborns. Allometric equations were calculated
      form 93 species of mammals: Mneo = 0.03374 M0.946 and Gt = 68.536 M0.225 (Mneo is
      the body weight of newborns in kg, M is the body weight of the female in kg and
      Gt is the gestational period in days). According to these allometric equations
      the birthweight of newborns is from 1100 g to 1600 g and gestational age is from
      22.4-24.5 weeks of gestation. The data from comparative zoology are in conformity
      with requirements of neonatologists to receive prematurity without further intra
      intrauterine pathologies. The postnatal care taken after extremely premature
      newborns replaces adaptive mechanisms which are present in immature mammalian
      newborns of r strategy. The neonatological practice has decreased the viability
      level to 24 weeks of gestation during the last 20 years. Further lowering to 22
      weeks is possible in the near future.

PMID- 9600160
TI  - [Diagnosis and therapy of male sterility (ESHRE Guidelines 1996)].

PMID- 9600161
TI  - [HIV infections in gynecology and obstetrics].

PMID- 9600162
TI  - [Relation of the duration of hormone replacement therapy and risk of breast
      carcinoma].

PMID- 9600163
TI  - [Tolerance and effectiveness of propiverine hydrochloride in 752 patients with
      symptoms of detrusor hyperactivity and increased sensitivity and irritability of
      the urinary bladder: results of a study monitoring drug utilization].
AB  - In a post-marketing surveillance study of 752 patients suffering from urgent
      incontinence, mixed urgent-stress incontinence, reflex incontinence, urgency and
      enuresis were treated with propiverine hydrochloride. Clinical efficacy of
      propiverine hydrochloride was verified by the improvement of symptoms related to
      detrusor hyperactivity, hypersensitivity and hyperreflexia during a 12-week
      surveillance period: daytime and overnight urinary incontinence, as well as the
      frequency, nocturia, urgency in day time and at night decreased. These results
      are well demonstrated by decreased pad use and statistically significant decrease
      of Gaudenz urgency score during treatment, confirming the efficacy of propiverine
      hydrochloride already proved in clinical trials. The safety profile of
      propiverine hydrochloride displayed characteristic anticholinergic symptoms (dry
      mouth, accommodation disorders, constipation, tiredness, dizziness) with
      decreasing incidence during the 12-week treatment period. The residual urine
      volume decreased also. Serious adverse events were observed rarely and could be
      explained by the lack of consideration of contraindications, warnings and
      interactions with other drugs. The positive risk-benefit relationship of
      propiverine hydrochloride in the treatment of detrusor hyperactivity,
      hypersensitivity and hyperreflexia was reconfirmed in this post-marketing drug
      surveillance study.

PMID- 9600164
TI  - [Importance of embryo cryopreservation in a program of in vitro fertilization:
      experience and results of 550 transfers of thawed embryos].
AB  - Results of 550 transfers of cryopreserved and thawed embryos were analyzed. A
      total number of 47 pregnancies was achieved (8.5% per embryo transfer).
      Significantly better results were obtained when no selection of embryos before
      cryopreservation was made (i.e. pronucleate stage embryos and patients with all
      embryos frozen) compared to the "spare embryos" group-14 pregnancies per 99
      transfers (14%) vs. 33 pregnancies per 451 transfers (7%) respectively.
      Cultivation of thawed embryos before embryo transfer has a beneficial effect on
      implantation-19 pregnancies per 121 transfers (16%) in the group of cultured
      embryos vs. 28 pregnancies per 429 transfers (7%) in the group without
      cultivation. Cryopreservation significantly contributes to the effectivity of IVF
      and provides further possibilities for conception in addition to those achieved
      from the fresh cycle.

PMID- 9600165
TI  - [Andrologic and non-andrologic indications for intracytoplasmic sperm injection
      (ICSI)].
AB  - Intracytoplasmic sperm injection (ICSI) is a very valuable method which implies a
      qualitative contribution to assisted reproduction and andrologically conditioned
      sterility, in particular. However, as one of the methods of cellular surgery it
      has its defined indications which must be respected.

PMID- 9600166
TI  - [The current role of intracytoplasmic single sperm injection (ICSI) in assisted
      reproduction].
AB  - Intracytoplasmic sperm injection (ICSI) plays a unique role in the treatment of
      male infertility. ICSI results are not influenced by either sperm number,
      motility or sperm morphology. In our group we studied 90 cycles in which
      conventional IVF and ICSI were performed on sibling oocytes in couples with
      borderline semen analysis (more than 50,000 sperm/oocyte). A higher number of A
      quality embryos was found in the ICSI oocyte group (40%/32%). In 38% of IVF
      cycles no embryos were found, whereas with ICSI the absence decreased to only
      12%. In only 4% of the cycles, the IVF method was more successful than that of
      ICSI treatment. In only 7% of our combined group there were no embryos for
      transfer. The positive influence of ICSI on our centre results -32% pregnancy
      rate/ET and an 18% baby take home rate--are discussed. In our retrospective
      study, ICSI is more successful than IVF alone and a combination of IVF and ICSI
      achieves the best results in the borderline sperm analysis group. An increased
      use of the ICSI technique in assisted reproduction can be expected in future.

PMID- 9600167
TI  - [Results of a study of serum hormones and biochemical findings in seminal plasma
      in subfertile men examined at the Clinic for Gynecology and Obstetrics in Olomouc
      1995-1996].
AB  - Based on a comparative study in a group of healthy men and men suffering from
      oligospermia and azoospermia, the authors consider it useful to examine FSH, LH,
      PRL and testosterone serum levels for possible evidence of testicular
      hypofunction and for detection of stress situations associated with raised PRL
      levels. As to seminal plasma, the authors consider it useful and relevant to
      assess citric acid levels, total acid phosphatases and in particular fructose
      with alpha-glucosidase.

PMID- 9600168
TI  - [Changes in the endometrium in treatment of breast carcinoma with tamoxifen].
AB  - A group of twenty postmenopausal breast cancer patients treated with tamoxifen
      was used for examination of the endometrial morphology, role of transvaginal
      sonography, and consequences of insufficient collaboration between gynaecologist
      and oncologist. One case of endometrial carcinoma, one case of abnormal
      hyperplasia, and ten endometrial polyps in asymptomatic patients support the need
      for routine transvaginal sonography as a screening method. Any uterine bleeding
      should be evaluated by hysteroscopy.

PMID- 9600169
TI  - [Are echogenic foci in fetal heart ventricles insignificant findings?].
AB  - In a group of 7,721 foetuses with a high or low risk of cardiovascular pathology
      of the foetus, examined by complete foetal echocardiography, the authors found
      hyperechogenic ventricular structures in 211 foetuses (2.73% of the group) with a
      dominating localization in the left ventricle (97%). These structures are in the
      great majority a benign development variant which involves no risk for the
      development of the foetus. Rare localization beyond the left ventricle were not
      risk for the development of the foetus. Rare localization beyond the left
      ventricle were not associated with cardiac or other foetal pathologies. Echogenic
      ventricular focuses were not visualized by transvaginal echocardiography in the
      13th week of pregnancy, although they were revealed in the same patient during
      the 21st week. Their presence does not affect left ventricular function and the
      function of the mitral valve pre-or postnatally. In the differential diagnosis
      these structures must be always differentiated from thrombi or cardiac tumours.

PMID- 9600170
TI  - [Algopareunia].
AB  - During treatment of chronic pelvic inflammatory diseases the authors examined by
      interviews conducted by two sexuologists in Frantiskovy Lazne 152 women married
      for at least one year, aged 21 to 40 years. After analysis of the results of
      sexuological examinations the authors recommend to use the term algopareunia for
      patients who have painful sensations during coitus but react rationally and are
      satisfied with their sex life. The term dyspareunia covers women who with regard
      to pain during intercourse report that they are dissatisfied with their sex life.

PMID- 9600171
TI  - [The "seat belt" syndrome in pregnancy. Possible prevention].

PMID- 9600172
TI  - [Diagnosis of endometrial pathology in perimenopause].

PMID- 9600173
TI  - [Injuries of the pelvic and abdominal vessels during radical gynecologic
      operations].

PMID- 9600174
TI  - [The HELLP syndrome].

PMID- 9600176
TI  - [GnRH antagonists--present state of development and possible use in clinical
      practice].

PMID- 9600175
TI  - [Sacral teratoma and the postnatal course].

PMID- 9600177
TI  - [Special cases of association of hormone replacement therapy with risk of breast
      carcinoma].

PMID- 9600178
TI  - [Misoprostol--a new prostaglandin for induction of labor?].

PMID- 9600179
TI  - [Fixation of the prolapsed vagina to the sacrospinous ligament after hysterectomy
      -the Amreich II-Richter vaginal fixation operation].
AB  - Preliminary experience with vaginal vault prolapse treatment with sacrospinous
      fixation (Amreich II-Richter) is described. Anatomical considerations having
      taking into account the method used by author are presented. From 1986 at the 1st
      Dept. of Obstetrics and Gynaecology 38 patients (20 of them after abdominal, 18
      after vaginal hysterectomy) with this rare condition were treated by the
      discussed operation. Similar to other authors a high success rate, 97.4%, was
      achieved and no major bleeding or injury of adjacent nerves occurred. One injury
      of the bladder, one of the rectum was solved during the operation and an
      infection of supravaginal haematoma was treated. This operation provides
      excellent results and a good vaginal support.

PMID- 9600180
TI  - [Ultrasound imaging of the urethral sphincter].
AB  - The integrity and functional capacity of the urethral sphincter is one of the
      important prerequisites of urinary incontinence in women. Urodynamic
      investigations revealed repeatedly that the maximum closure pressure in the
      median portion of the urethra corresponds to the maximal thickness of the
      external urethral sphinctor (rhabdosphincter urethrae). This striated muscle is
      adapted to maintain a relatively steady tonus which assists the closure mechanism
      of the urethra [4]. In the submitted study the authors focused attention on the
      ultrasonic visualization of the internal urethral sphincter in order to assess
      the relationship between the size of this sphincter and the stress type of
      incontinence (genuine stress incontinence-GSI). The investigation comprised
      thirty women with confirmed GSI and a control group of thirty asymptomatic
      volunteers. During perineal ultrasonic examination of women in a supine position
      by means of an ACUSON 128 XP 10 apparatus using a convex probe with a frequency
      of 5 MHz the authors recorded statistically significant differences in the areas
      and maximal thickness of the urethral sphincter in women with stress incontinence
      and symptom-free women. From the results ensues that the size of this muscle is
      much smaller in women suffering from GSI.

PMID- 9600181
TI  - [Changes in levels of cell adhesion molecules, acute phase proteins, lipids and
      hemostasis in relation to levels of endogenous estrogens during pregnancy and
      after ovariectomy].
AB  - The protective effect of oestrogens is probably caused also by the active
      inhibition of the inflammatory reaction of the acute phase and release of
      inflammatory cytokines type IL-1 beta or TNF-alpha by this hormone. We formulated
      this hypothesis because we recorded a drop of the protein of the acute stage,
      orosomucoid, in relation to the rising oestrogen level during pregnancy (r = 
      0.511, p < 0.0001). It ensues also from the finding of a lower level of
      cytoadhesive molecules of sE-selectins in a group of 66 pregnant women (sE-sel.:
      32.95 +/- 12.5 ng/ml) with a higher level of 17-beta estradiol (17-beta E2: 9.34
      +/- 7.8 nmol/l), as compared with the sE-selectin level in a group of 14 women
      after ovariectomy (sE-sel.: 43.97 +/- 8.174 ng/ml, p < 0.016) who lacked
      oestrogen (17-beta E2 0.14 +/- 0.13 nmol/l) and in a group of pregnant women (n
      19) in the first trimester with level of 17-beta E2: 1.89 +/- 0.711 nmol/l where
      the sE-selectin concentrations at the onset pregnancy was higher (sE-sel.: 35.59
      +/- 9.5 ng/ml) than in a group of pregnant women (n 38) during the second and
      third trimester (sE-sel.: 30.58 +/- 13.3 ng/ml, p < 0.05) with 17-beta E2
      concentration 11.96 +/- 7.18 ng/ml. The finding of lower sE-selectin levels which
      is a sign that the endothelium is not exposed to the action of inflammatory
      cytokines IL-1 or TNF may thus be associated with the active "control" of
      thrombophilia in pregnancy. When during pregnancy in conjunction with oestrogen
      levels changes in the lipid concentration were investigated a compensating
      mechanism could be observed. Hypercholesterolaemia and hypertriglyceridaemia in
      pregnant women was associated with a rise of oestrogen levels as well as of
      "cardioprotective" HDL-cholesterol (the HDL level was during the first trimester
      1.31 +/- 0.26 nmol/l, in the second and third trimester 1.69 +/- 0.48 nmol/l, p <
      0.0167).

PMID- 9600182
TI  - [Sactosalpinx, one of the factors affecting the results of in vitro
      fertilization].
AB  - The tubal factor of sterility is nowadays already a classical and also the most
      frequent indication for including the patient in a programme of in vitro
      fertilization--embryo transfer (IVF-ET) [3]. Tubal sterility has a multifactorial
      etiology. The causes include unilateral or bilateral sactosalpinx, distal and
      proximal obstructions, intraluminal or extramural adhesions. In many patients
      with damaged oviducts who were included in our IVF programme we recorded
      repeatedly failures despite an adequate ovarian response to the stimulation by
      menogonadotropins, uncomplicated collection of oocytes, equal numbers of
      collected oocytes, similar fertilization and embryo transfer of high standard
      embrya. In this group of patients sactosalpinx was frequently encountered. Recent
      investigations assume that the presence of sactosalpinx reduces the implantation
      rate, pregnancy rate, increases early gestation losses and the incidence of
      extrauterine pregnancies [12, 5, 14]. In the submitted paper the authors
      evaluated the possible effect of sactosalpinx on the results of the IVF-ET
      programme.

PMID- 9600183
TI  - [Incidence of renal agenesis in the Czech Republic from 1961 to 1995].
AB  - During the period between 1961 and 1995 the incidence of renal agenesis in the
      Czech Republic was investigated. From a consecutive series of 5,137,907 births in
      the Czech Republic in 1961-1995 915 cases of renal agenesis were diagnosed, incl.
      859 in born infants and 56 cases were diagnosed prenatally and the pregnancies
      were terminated. The mean incidence of renal agenesis in born infants during the
      follow up period was 1.66 per 10,000 liveborn infants, after adding the results
      of prenatal diagnosis the mean incidence was 2.02 per 10,000 liveborn infants.
      The authors investigated also the prenatal diagnosis of renal agenesis in the
      Czech Republic. The rate of diagnosis of renal agenesis was on average in 1988-95
      in the Czech Republic more than 26% detected cases.

PMID- 9600184
TI  - [Induction of pulmonary tissue maturation in premature infants].

PMID- 9600185
TI  - [Importance of determination of activated protein C resistance (APC) in
      gynecology and obstetrics].

PMID- 9600186
TI  - [Ultrasound examination of the lower urinary tract in women].

PMID- 9600187
TI  - [Syphilis in pregnancy--a modern epidemiologic problem].

PMID- 9600188
TI  - [Hormone replacement and risk of breast carcinoma in a high-risk group of women].

PMID- 9600189
TI  - [Uterine sarcomas].

PMID- 9600190
TI  - [Reproductive health in girls and women (survey of Czech gynecologists). Final
      report by the Medicus pro Femina Society (April 1997)].

PMID- 9600191
TI  - Neuronal control of the immune response in the central nervous system: linking
      brain immunity to neurodegeneration.

PMID- 9600192
TI  - The histopathological and clinical relevance of apoptotic cell death in
      medulloblastomas.
AB  - We studied apoptosis in 40 medulloblastomas by in situ end labeling (ISEL) of DNA
      strand breaks. In situ end labeling was performed on paraffin-embedded material
      from classical and desmoplastic medulloblastomas and medulloblastomas with glial
      and combined differentiation. The number of labeled apoptotic cells varied
      considerably from tumor to tumor as well as between different areas in the same
      tumor. However, there was no significant difference in the averaged numbers or in
      the pattern of apoptotic tumor cells between the different differentiations of
      medulloblastoma. Unlabeled tumor cells displaying features of apoptosis were
      found in small numbers, indicating that tumor cells may also be able to undergo
      cell death different from classical apoptosis. A significantly higher number of
      apoptotic tumor cells in male patients could be demonstrated corresponding to the
      reported difference in survival rates between male and female patients suffering
      from medulloblastoma. A clear cut trend of a negative relation between apoptosis
      and age by operation was found.

PMID- 9600193
TI  - Factors that affect the expression of beta-amyloid precursor protein
      immunoreactivity in the rat retina.
AB  - Expression of beta-amyloid precursor protein immunoreactivity in the rat retina
      was studied after intravitreal injection of substances known to influence neural
      function in different ways. The substances were the excitatory amino acid
      glutamate, the inflammatory agent lipopolysaccharide, the depolarizing agent
      potassium chloride, and the potassium channel blocker barium chloride. In
      comparison with controls, more beta-amyloid precursor protein immunoreactivity
      was observed in the radial process of Muller glial cells 24 hours after injection
      of glutamate or lipopolysaccharide. In contrast, administration of barium
      chloride greatly reduced immunostaining in Muller cells. Further, an increase in
      immunostaining was observed in the inner and outer plexiform layers in retinas
      treated with any of the 3 chemicals, and in blood vessels after injection of
      glutamate and lipopolysaccharide. These observations suggest that multiple but
      specific signaling pathways are involved in regulating expression of beta-amyloid
      precursor protein in distinct cell types and regions in the retina.

PMID- 9600194
TI  - Altered neuronal activity rhythm and glutamate receptor expression in the
      suprachiasmatic nuclei of Trypanosoma brucei-infected rats.
AB  - The parasites Trypanosoma brucei cause African trypanosomiasis (sleeping
      sickness), a severe neuropsychiatric disease with marked disturbances of sleep
      wake alternation. The sites of brain lesions are not well characterized. The
      present experimental investigation is focused on the hypothalamic suprachiasmatic
      nuclei, which play a role of a biological clock entraining endogenous rhythms in
      the mammalian brain. The electrophysiological properties of these neurons were
      analyzed in slice preparations from trypanosome-infected rats. The neuronal
      spontaneous activity, which shows a circadian oscillation, was markedly altered
      in the infected animals, displaying a reduced firing rate and phase advance of
      its circadian peak. The direct retinal fibers, which play a pivotal role in
      entrainment of the circadian pacemaker, displayed a normal density and
      distribution in the suprachiasmatic nuclei of infected animals after intraocular
      tracer injections in vivo. At the postsynaptic level, immunohistochemistry and
      Western blotting revealed in the suprachiasmatic nuclei of infected rats a
      selective decrease of the expression of glutamate AMPA GluR2/3 and NMDAR1
      receptor subunits that gate retinal afferents. These data disclose an impairment
      of the neuronal functions in the biological clock in African trypanosomiasis, and
      may serve to unravel functional and molecular mechanisms behind endogenous rhythm
      disturbances.

PMID- 9600195
TI  - Diagnosis of intracranial vasculitis: a multi-disciplinary approach.
AB  - Intracranial vasculitis, or primary angiitis of the central nervous system
      (PACNS), is an uncommon, often fatal disorder that frequently responds to
      aggressive immunosuppressive therapy. Magnetic resonance imaging (MRI), cerebral
      angiography, and brain biopsy are diagnostic modalities that vary in invasiveness
      and diagnostic accuracy. The purpose of this study was to determine whether
      certain clinical or radiologic features were predictive of a diagnostic biopsy.
      Thirty consecutive patients undergoing brain biopsy to "rule out vasculitis" were
      studied. Nine patients demonstrated granulomatous or lymphocytic vasculitis, 1
      had lymphocytic vasculitis and encephalitis secondary to arbovirus infection, 5
      had thickened vessels consistent with hypertensive changes, 5 had amyloid
      angiopathy and/or changes of Alzheimer disease, 5 demonstrated no pathologic
      abnormalities, and 1 each had acute infarct, vascular malformation, aneurysm,
      acellular fibrinoid necrosis, and demyelination. The spectrum of MRI and
      angiographic changes associated with PACNS were nonspecific, overlapping
      extensively with changes of chronic hypertension and amyloid deposition. The
      predictive values of brain biopsy (90-100%) were significantly higher than those
      of angiography (37-50%) or MRI (43-72%). In this study, morbidity associated with
      aggressive immunosuppression was significantly greater than that associated with
      cerebral angiography or brain biopsy. Thus, wedge biopsy of cortical and
      leptomeningeal tissues is central to the multi-disciplinary approach to a patient
      with clinical suspicion of PACNS.

PMID- 9600196
TI  - Neuropathologic evidence that the Lewy body variant of Alzheimer disease
      represents coexistence of Alzheimer disease and idiopathic Parkinson disease.
AB  - We undertook this study to investigate the neuropathologic relationships among
      Alzheimer disease (AD), idiopathic Parkinson disease (PD), and the Lewy body
      variant of AD (AD/LBV). We retrieved 30 autopsy cases in which Lewy bodies (LB)
      had been identified in the substantia nigra (SN) in routine hematoxylin-eosin
      stained sections. Twenty-two of the cases had a primary clinical diagnosis of
      dementia and neuropathologic changes of AD; 12 of these demented patients also
      had clinical parkinsonism. Eight cases had clinical and neuropathologic evidence
      of PD with minimal or no AD neuropathology, though 6 had clinical dementia.
      Controls consisted of 6 cases of AD without SN LB by hematoxylin-eosin, and 5
      neurologically normal aged controls. Paraffin sections of SN, superior temporal
      gyrus, and cingulate gyrus from each case were immunostained with rabbit anti
      ubiquitin antiserum, randomized, and analyzed individually by light microscopy,
      and the density of LB-like profiles in each section were graded. None of 5
      nondemented aged controls showed any neocortical LB, even though 2 had
      significant numbers of incidental SN LB by ubiquitin immunostaining. Of 6 AD
      cases without SN LB by hematoxylin-eosin, 3 had rare SN LB on ubiquitin stain, 1
      of which showed rare neocortical Lewy-like profiles. Seven of 8 PD cases showed
      neocortical LB, including the 6 with dementia. Twenty-one of 22 AD cases with SN
      LB showed ubiquitin-immunoreactive Lewy-like bodies in the neocortex that were
      statistically significantly greater in number than in either pure PD or pure AD
      cases. The frequent occurrence of LB in the neocortex in PD alone suggests that
      AD/LBV likely represents mixed AD/PD. However, AD neuropathology may favor or
      promote the formation of neocortical LB in patients who go on to develop mixed
      AD/PD pathology.

PMID- 9600197
TI  - Induced expression of NMDAR2 proteins and differential expression of NMDAR1
      splice variants in dysplastic neurons of human epileptic neocortex.
AB  - Immunocytochemistry was used to study the expressions of glutamate receptor
      subunit proteins for NMDAR2A/B, NMDAR1 splice variants, and AMPA Glu-R2/3 in
      human brain resected for intractable epilepsy associated with cortical dysplasia.
      NMDAR2A/B intensely labeled dysplastic neurons showing staining in both the cell
      bodies and dendritic profiles. However, nondysplastic neurons were not
      immunoreactive to NMDAR2A/B. The antibody selective to NMDAR1 splice variants of
      NR1-1a. -1b, -2a, and -2b labeled dysplastic neurons, but few nondysplastic
      neurons. In contrast, the antibody to splice variants of NR1-1a, -1b, 2a, -2b, 
      3a, -3b, -4a, and -4b labeled both dysplastic and nondysplastic neurons. The
      different labeling patterns by these two antibodies indicate that variants of
      NMDAR1-3a, -3b, -4a, and -4b are present in nondysplastic neurons. Both
      dysplastic neurons and nondysplastic neurons were immunoreactive to AMPA GluR2/3,
      but denser immunoreactivity was observed in dysplastic neurons. We also found
      that the locations of dysplastic neurons labeled by NMDAR2A/B were related to
      focal epileptic EEG seizure onsets or spiking and to focal behavioral seizure
      types. Our results suggest that there is hyperexcitability of dysplastic cortical
      regions, at least in part, from the presence of NMDAR2 subunits and selectively
      expressed NMDAR1 splice variants in dysplastic neurons.

PMID- 9600198
TI  - Relationship between plaques, tangles, and loss of cortical cholinergic fibers in
      Alzheimer disease.
AB  - Recent observations in our laboratory have indicated substantial and systematic
      regional variations in the loss of cortical cholinergic fibers in Alzheimer
      disease (AD). Previous attempts to study the relationship between cortical
      cholinergic loss and the density of cortical pathological lesions have resulted
      in conflicting findings. Furthermore, most reports have correlated density of
      plaques and tangles with the residual level of cholinergic innervation rather
      than its loss. The purpose of the present study was to determine the relationship
      between loss of cholinergic axons and density of tangles and beta-amyloid (Abeta)
      deposits in various cortical areas of AD brains. Abeta deposits and tangles were
      observed throughout the cerebral cortex. Quantitative analysis revealed almost no
      correlation between loss of cholinergic fibers and the density of Abeta deposits.
      Qualitative observations revealed similar results when cored and neuritic plaques
      were considered separately. By contrast, cholinergic fiber loss displayed a
      significant correlation with the density of tangles (r = 0.52-0.79). However, in
      a few areas, such as the cingulate cortex, tangle density appeared to be
      unrelated to the loss of cholinergic fibers. These results indicate that cortical
      cholinergic denervation in AD is related to cytoskeletal pathology. However, the
      lack of a perfect relationship with cytoskeletal pathology implicates additional
      factors in the cholinergic pathology of AD.

PMID- 9600199
TI  - N-terminal heterogeneity of parenchymal and cerebrovascular Abeta deposits.
AB  - The goals of this study were twofold: to determine whether species differences in
      Abeta N-terminal heterogeneity explain the absence of neuritic plaques in the
      aged dog and aged bear in contrast to the human; and to compare Abeta N-terminal
      isoforms in parenchymal vs cerebrovascular Abeta (CVA) deposits in each of the
      species, and in individuals with Alzheimer disease (AD) vs nondemented
      individuals. N-terminal heterogeneity can affect the aggregation, toxicity, and
      stability of Abeta. The human, polar bear, and dog brain share an identical Abeta
      amino acid sequence. Tissues were immunostained using affinity-purified
      polyclonal antibodies specific for the L-aspartate residue of Abeta at position
      one (AbetaN1[D]), D-aspartate at N1 (AbetaN1[rD]), and pyroglutamate at N3
      (AbetaN3[pE]) and p3, a peptide beginning with leucine at N17 (AbetaN17[L]). The
      results demonstrate that each Abeta N-terminal isoform can be present in diffuse
      plaques and CVA deposits in AD brain, nondemented human, and the examined aged
      animal models. Though each Abeta N-terminal isoform was present in diffuse
      plaques, the average amyloid burden of each isoform was highest in AD vs polar
      bear and dog (beagle) brain. Moreover, the ratio of AbetaN3(pE) (an isoform that
      is resistant to degradation by most aminopeptidases) vs AbetaN17(L)-x (the
      potentially nonamyloidogenic p3 fragment) was greatest in the human brain when
      compared with aged dog or polar bear. Neuritic plaques in AD brain typically
      immunostained with antibodies against AbetaN1(D) and AbetaN3(pE), but not
      AbetaN17(L) or AbetaN1(rD). Neuritic deposits in nondemented individuals with
      atherosclerotic and vascular hypertensive changes could be identified with
      AbetaN1(D), AbetaN3(pE), and AbetaN1(rD). The presence of AbetaN1(rD) in neuritic
      plaques in nondemented individuals with atherosclerosis or hypertension, but not
      in AD, suggests a different evolution of the plaques in the two conditions.
      AbetaN1(rD) was usually absent in human CVA, except in AD cases with
      atherosclerotic and vascular hypertensive changes. Together, the results
      demonstrate that diffuse plaques, neuritic plaques, and CVA deposits are each
      associated with distinct profiles of Abeta N-terminal isoforms.

PMID- 9600200
TI  - Commentary to: Differences between the pathogenesis of senile plaques and
      congophilic angiopathy in Alzheimer disease. (J Neuropathol Exp Neurol 1997;
      56:751-61)

PMID- 9600201
TI  - A4 amyloid is toxic to neuronal processes.

PMID- 9600202
TI  - The neuropathology of alcohol-specific brain damage, or does alcohol damage the
      brain?
AB  - The aim of this review is to identify neuropathological changes that are directly
      related to the long-term use of excessive amounts of alcohol (ethanol). There is
      still debate as to whether alcohol per se causes brain damage. The main problem
      has been to identify those lesions caused by alcohol itself and those caused by
      other common alcohol-related factors, principally thiamin deficiency. Careful
      selection and classification of alcoholic cases into those with and without these
      complications, together with detailed quantitative neuropathological analyses,
      has provided us with useful data. There is brain shrinkage in uncomplicated
      alcoholics which can largely be accounted for by loss of white matter. Some of
      this damage appears to be reversible. However, alcohol-related neuronal loss has
      been documented in specific regions of the cerebral cortex (superior frontal
      association cortex), hypothalamus (supraoptic and paraventricular nuclei), and
      cerebellum. The data is conflicting for several regions: the hippocampus,
      amygdala and locus ceruleus. No change is found in the basal ganglia, nucleus
      basalis, or serotonergic raphe nuclei. Many of the regions that are normal in
      uncomplicated alcoholics are damaged in those with the Wernicke-Korsakoff
      syndrome. Dendritic and synaptic changes have been documented in uncomplicated
      alcoholics and these, together with receptor and transmitter changes, may explain
      functional changes and cognitive deficits that precede the more severe structural
      neuronal changes. The pattern of damage appears to be somewhat different and
      species-specific in animal models of alcohol toxicity. Pathological changes that
      have been found to correlate with alcohol intake include white matter loss and
      neuronal loss in the hypothalamus and cerebellum.

PMID- 9600203
TI  - Age-related phosphorylation and fragmentation events influence the distribution
      profiles of distinct tau isoforms in mouse brain.
AB  - Native tau isoforms were analyzed in adult mouse brain to determine whether they
      are differentially distributed and to identify molecular alterations that modify
      individual isoforms in an age-dependent manner. In general, the distribution
      profiles of 42-50 kDa tau were distinct from those of larger, hyperphosphorylated
      species of 55-69 kDa. The hippocampus and neocortex had concentrated levels of 55
      kDa tau, and moderate amounts of 62-69 kDa isoforms. The latter species were
      similarly expressed in thalamic and hindbrain tissue; however, the noncortical
      regions were uniquely enriched in high molecular weight tau (97-110 kDa). When
      assessing hippocampal tau across age, increasing levels of 69 kDa tau were found
      to correlate with a gradual reduction in 42-50 kDa isoforms. Endogenous
      phosphatase activity induced an opposite correlation, thus supporting the idea
      that certain isoform conversions that occur with age stem from
      hyperphosphorylation. Age-related increases in 69 and 97 kDa tau also
      corresponded to enhanced levels of tau29, a putative tau fragment that exhibited
      an atypical localization (concentrated in olfactory bulb and hindbrain samples).
      These findings indicate that phosphorylation and fragmentation events influence
      tau distribution patterns, and that the former modification may promote the
      latter They also raise the possibility that brain regions targeted by Alzheimer
      disease are distinguished by distinct tau profiles.

PMID- 9600204
TI  - Molecular genetic correlates of p16, cdk4, and pRb immunohistochemistry in
      glioblastomas.
AB  - The vast majority of glioblastomas have CDKN2A, CDK4, or RB gene alterations that
      perturb the p16-cdk4-pRb cell cycle regulatory cascade. To explore whether
      immunohistochemical methods provide an alternative means of assessing this
      pathway, we studied 25 glioblastomas using a combination of molecular genetic and
      immunohistochemical assays. Homozygous deletion of the CDKN2A gene was detected
      in 12 of 25 (48%) cases, CDK4 amplification in 4 of 25 (16%) tumors, and loss of
      heterozygosity at the RB gene in 8 of 22 (36%) informative cases. Five of 25
      (20%) glioblastomas had diffuse p16 immunohistochemical positivity.
      Significantly, all of these had either CDK4 amplification or RB LOH, suggesting
      that p16 immunopositivity only occurs in those tumors with alterations of another
      component in the pathway. Nineteen (76%) cases were uniformly immunonegative for
      p16, and 12 (48%) had CDKN2A homozygous deletions, but the remaining 7 cases
      lacked CDKN2A deletions, mutations and promoter methylation. All glioblastomas
      stained diffusely for cdk4, irrespective of CDK4 gene amplification status.
      Extensive pRb staining was present in most cases that maintained both RB alleles,
      and absent in most cases with RB loss, but there were notable discrepancies.
      Thus, p16 and pRb immunohistochemistry cannot replace molecular genetic analysis
      of this critical regulatory cascade; instead, the combined results hint at
      complex regulation of this cell cycle checkpoint. From a practical point of view,
      although p16 immunonegativity does not necessarily indicate CDKN2A deletion,
      diffuse positive p16 immunostaining strongly suggests either CDK4 amplification
      or RB loss and excludes CDKN2A deletion.

PMID- 9600205
TI  - Constitutive and cytokine-inducible expression of prion protein gene in human
      neural cell lines.
AB  - Prion diseases are a group of neurodegenerative disorders characterized by
      intracerebral accumulation of a protease-resistant prion protein (PrP(Sc)) that
      causes extensive neuronal degeneration and astrogliosis. The regulation of prion
      protein (PrP) gene expression by a panel of glial and neuronal cytokines (TNF
      alpha, IFN-gamma, IL-1beta, IL-10, and TGF-beta1) was investigated in human
      neural cell lines by reverse transcription-polymerase chain reaction and Northern
      blot analysis. The constitutive expression of PrP mRNA was identified in all
      human neural cell lines and tissues examined including Y79 retinoblastoma, IMR-32
      neuroblastoma, SK-N-SH neuroblastoma, U-373MG astrocytoma, KG-1-C glioma, NTera2
      teratocarcinoma, NTera2-derived differentiated neurons (NTera2-N), peripheral
      nerve, and cerebral and cerebellar tissues. In SK-N-SH cells, a 48 hour (h)
      treatment with 100 ng/ml IL-1beta, 100 ng/ml TNF-alpha, or 100 nM phorbol 12
      myristate 13-acetate induced a 2.7- to 4.2-fold increase in the level of PrP
      mRNA, while the exposure to 100 ng/ml IFN-gamma resulted in a 50% decrease. By
      contrast, none of these cytokines significantly altered the levels of PrP mRNA in
      IMR-32, NTera2-N, or U-373MG cells. These results indicate that the PrP gene
      expression is constitutive in a wide range of human neural cell lines and tissues
      where it is controlled by cell type-specific regulatory mechanisms.

PMID- 9600206
TI  - Laser microprobe mass spectrometric study of aluminum and silicon in brain emboli
      related to cardiac surgery.
AB  - Recent investigations have shown numerous fatty microemboli, which we previously
      termed small capillary and arteriolar dilatations (SCADs), in brain microvessels
      of patients who died after cardiac surgery assisted by cardiopulmonary bypass
      (CPB). The hypothesis of this study was that extraneous trace elements such as
      aluminum (Al) and silicon (Si) might be contaminating the blood and causing the
      formation of SCADs or coating the SCADs already formed in the extracorporeal
      circulation during CPB. Small capillary and arteriolar dilatations were
      identified in thick celloidin sections of the brains of 8 patients who died after
      cardiac surgery supported with a membrane oxygenator, and of 2 dogs that
      underwent CPB with a bubble oxygenator. The sections were infiltrated with
      Spurr's embedding medium for electron microscopy. Resin sections 0.5 microm thick
      were placed on 100-mesh copper grids and analyzed with laser microprobe mass
      spectrometry. Brain sections without SCADs from 3 patients (controls) whose
      deaths were not related to cardiac surgery were processed similarly. In SCADs and
      nearby neuropil sites of the 8 patients who had cardiac surgery, both Al and Si
      values were higher than in the neuropil, including vessels of the 3 controls. Si
      values were also high in the 2 dogs, in which a bubble oxygenator was used. Our
      results indicate that contamination with Al and Si continues to occur during
      cardiac surgery assisted by CPB. Our data also suggest that switching to membrane
      oxygenators from bubble oxygenators for CPB may have reduced Si contamination of
      blood. Further refinements of CPB aimed at eliminating microemboli formation and
      Al and Si entry into the circulation are warranted.

PMID- 9600207
TI  - Caprine mucopolysaccharidosis-IIID: clinical, biochemical, morphological and
      immunohistochemical characteristics.
AB  - Several animal models have been developed for the mucopolysaccharidoses (MPSs), a
      group of lysosomal storage disorders caused by lysosomal hydrolase deficiencies
      that disrupt the catabolism of glycosaminoglycans (GAG). Among the MPS, the MPS
      III (Sanfilippo) syndromes lacked an animal counterpart until recently. In this
      investigation of caprine MPS-IIID, the clinical, biochemical, morphological, and
      immunohistochemical studies revealed severe and mild phenotypes like those
      observed in human MPS III syndromes. Both forms of caprine MPS IIID result from a
      nonsense mutation and consequent deficiency of lysosomal N-acetylglucosamine 6
      sulfatase (G6S) activity and are associated with tissue storage and urinary
      excretion of heparan sulfate (HS). Using special stains, immunohistochemistry,
      and electron microscopy, secondary lysosomes filled with GAG were identified in
      most tissues from affected goats. Primary neuronal accumulation of HS and the
      secondary storage of gangliosides were observed in the central nervous system
      (CNS) of these animals. In addition, morphological changes in the CNS such as
      neuritic expansions and other neuronal alterations that may have functional
      significance were also seen. The spectrum of lesions was greater in the severe
      form of caprine MPS IIID and included mild cartilaginous, bony, and corneal
      lesions. The more pronounced neurological deficits in the severe form were partly
      related to a greater extent of CNS dysmyelination. These findings demonstrate
      that caprine MPS IIID is a suitable animal model for the investigation of
      therapeutic strategies for MPS III syndromes.

PMID- 9600208
TI  - Neurotrophin sensitivity of prevertebral and paravertebral rat sympathetic
      autonomic ganglia.
AB  - Prevertebral and paravertebral sympathetic autonomic ganglia respond differently
      to a large number of experimental and clinical insults. The selective involvement
      of subpopulations of sympathetic neurons may reflect differences in their
      response to neurotrophic substances. To test this hypothesis, we investigated the
      response of prevertebral and paravertebral rat sympathetic ganglia to selected
      neurotrophic substances in vivo and in vitro and identified the ganglionic
      distribution of neurons expressing high affinity neurotrophin receptor mRNAs.
      Dissociated cultures of embryonic prevertebral and paravertebral ganglionic
      neurons showed comparable responses to NGF deprivation and only small differences
      in their response to rescue with other trophic substances. In situ hybridization
      studies of adult rat sympathetic ganglia using probes specific for the high
      affinity neurotrophin receptor transcripts trks A, B, and C demonstrated that
      neurons in both prevertebral and paravertebral sympathetic ganglia express
      predominantly trkA receptors in vivo. In addition, increased tyrosine hydroxylase
      (TOH) activity was induced only by doses of neurotrophic substances that activate
      trkA and showed only small differences between neonatal prevertebral and
      paravertebral ganglia. Although small differences in the sensitivity of pre- and
      paravertebral sympathetic neurons to various neurotrophins have been identified
      in our studies, they are unlikely, in isolation, to explain major differences in
      the sensitivity of these ganglia to neuropathologic processes.

PMID- 9600209
TI  - Transcription factor NF-kappaB and inhibitor I kappaBalpha are localized in
      macrophages in active multiple sclerosis lesions.
AB  - NF-kappaB is a transcription factor family which on translocation to the nucleus
      regulates gene expression during cell activation. As such, NF-kappaB may play a
      role in the microglial response to myelin damage in multiple sclerosis (MS)
      lesions. Here the cellular localization of NF-kappaB and expression of the
      inhibitory I kappaBalpha were examined by immunocytochemistry on central nervous
      system (CNS) tissue from MS and control cases. In normal control white matter,
      the active form of the NF-kappaB subunit RelA (p65) was localized in microglial
      nuclei, while the c-Rel and p50 subunits and the inhibitory I kappaBalpha were
      restricted to the cytoplasm. In contrast, in actively demyelinating plaques, the
      RelA, c-Rel, and p50 subunits of NF-kappaB and I kappaBalpha were all present in
      macrophage nuclei in both parenchymal and perivascular areas. RelA was also found
      in the nuclei of a subset of hypertrophic astrocytes. Only c-Rel had a nuclear
      localization in lymphocytes in perivascular inflammatory cuffs. Our results
      suggest that constitutive activation of the RelA subunit in the nuclei of resting
      microglia may facilitate a rapid response to pathological stimuli in the CNS.
      Activation of the inducible NF-kappaB pool in macrophages in MS lesions could
      amplify the inflammatory reaction through upregulation of NF-kappaB-controlled
      adhesion molecules and cytokines.

PMID- 9600210
TI  - Primitive neuroectodermal tumors of the cerebral hemispheres in two siblings with
      TP53 germline mutation.
AB  - AWe report on two siblings (brother and sister) who developed cerebral PNETs at
      the age of 5 years and 6 months, respectively. Both children were treated by
      operation followed by polychemotherapy. The brother also received cranio-spinal
      irradiation. Nevertheless, the children died about 12 months and 24 months post
      operatively due to extensive cerebral tumor recurrences. Shortly after having
      lost both of her children, the mother developed an intra-abdominal tumor, which
      was resected and histologically diagnosed as ovarian carcinoma. Because of this
      unusual familial clustering of tumors and a positive history of brain tumors and
      other cancers in several maternal relatives, we analyzed DNA isolated from both
      PNETs and the ovarian carcinoma as well as constitutional (leukocyte) DNA from
      the whole family for mutation of the TP53 tumor suppressor gene. This analysis
      revealed that all tumors were homozygous for a missense mutation at codon 213
      (CGA => TGG) resulting in an amino acid exchange from arginine to tryptophane.
      The same mutation was present in one TP53 allele in the constitutional DNA of the
      mother and the children, indicating that the mother had transmitted a TP53
      germline mutation to both of her children. Analysis of loss of heterozygosity at
      microsatellite markers from 17p confirmed deletion of the paternal (wild-type)
      allele in both PNETs. Further investigation of the PNETs by comparative genomic
      hybridization revealed multiple chromosomal abnormalities. Interestingly, some
      genomic changes were common to both PNETs, while many others were not, a finding
      suggesting substantial genomic instability, probably as a consequence of p53
      inactivation.

PMID- 9600211
TI  - Spontaneous congenital hydrocephalus in the mutant mouse hyh. Changes in the
      ventricular system and the subcommissural organ.
AB  - The subcommissural organ is an ependymal gland located at the entrance of the
      cerebral aqueduct. It secretes glycoproteins into the cerebrospinal fluid, where
      they aggregate to form Reissner's fiber. This fiber grows along the aqueduct,
      fourth ventricle, and central canal. There is evidence that the subcommissural
      organ is involved in the pathogenesis of congenital hydrocephalus. This organ was
      investigated in the mutant mouse hyh developing a congenital hydrocephalus. The
      central nervous system of normal and hydrocephalic hyh mice, 1 to 40 days old,
      was investigated using antibodies recognizing the subcommissural organ secretory
      glycoproteins, and by transmission and scanning electron microscopy. At birth,
      the affected mice displayed open communications between all ventricles, absence
      of a central canal in the spinal cord, ependymal denudation of the ventricles,
      stenosis of the rostral end of the aqueduct, and hydrocephalus of the lateral and
      third ventricles and of the caudal end of the aqueduct. Around the 5th postnatal
      day, the communication between the caudal aqueduct and fourth ventricle sealed,
      and hydrocephalus became severe. It is postulated that the hyh mice carry a
      genetic defect affecting the ependymal cell lineage. The subcommissural organ
      showed signs of increased secretory activity; it released to the stenosed
      aqueduct a material that aggregated, but it did not form a Reissner's fiber. A
      large area of the third ventricular wall differentiated into a secretory ependyma
      synthesizing a material similar to that secreted by the subcommissural organ. It
      is concluded that the subcommissural organ changes during hydrocephalus; whether
      these changes precede hydrocephalus needs to be investigated.

PMID- 9600212
TI  - The extracellular matrix in multiple sclerosis lesions.
AB  - Receptor-mediated recognition of extracellular matrix (ECM) molecules transduces
      intracellular signals that determine many cellular behaviors under normal and
      pathological conditions. This review briefly describes the major central nervous
      system (CNS) white matter ECM molecules and their receptors, the mechanisms by
      which the ECM may be altered in multiple sclerosis (MS) lesions, and potential
      roles for inflammatory and CNS resident cell interactions with specific ECM
      molecules in these lesions. In acute lesions, ECM recognition and cell signaling
      contribute to leukocyte migration through blood vessel walls, and within the CNS,
      through leukocyte and CNS resident cell immune activation and demyelination. An
      abnormal ECM in chronic MS lesions may preclude ECM-dependent developmental
      processes that lead to remyelination and axon regeneration. Thus, the composition
      of the ECM and the cellular recognition of its individual components may be
      critical to the pathogenesis of all stages of MS. An understanding of these
      complex interactions may lead to additional strategies for intervention and the
      promotion of reparative processes in MS patients.

PMID- 9600213
TI  - Dystrophic neurites of senile plaques are defective in proteins involved in
      exocytosis and neurotransmission.
AB  - Dystrophic neurites are major components of neuritic (both immature and mature)
      senile plaques in Alzheimer disease. Previous studies have shown strong
      immunoreactivity for different neuropeptides, and chromogranin A, a protein
      associated with dense-core vesicles, in dystrophic neurites. In the present
      study, antibodies to synaptophysin, synapsin, Rab3a and synaptotagmin (synaptic
      vesicle proteins), and SNAP-25 (synaptosomal-associated protein of 25 kD) and
      syntaxin (presynaptic plasma membrane proteins) have been used to learn about the
      dystrophic neurite equipment of proteins that are necessary for the docking and
      fusion of synaptic vesicles, and then for exocytosis and neurotransmission. The
      present results have shown that, although most neuritic senile plaques have
      chromogranin A- and SNAP-25-immunoreactive dystrophic neurites, only a percentage
      of them contain synaptophysin, and a minority contain synaptotagmin and Rab3a.
      Dystrophic neurites do not contain synapsin and syntaxin. These results show that
      dystrophic neurites of senile plaques are defective in proteins that control
      exocytosis and neurotransmission.

PMID- 9600214
TI  - Overexpression of Ki-67 and cyclins A and B1 in JC virus-infected cells of
      progressive multifocal leukoencephalopathy.
AB  - Both SV40 and JC virus (JCV) appropriate the host cell replicative machinery to
      attend to their own reproductive needs. SV40 large T antigen is able to induce
      the expression of cyclins A, B1, and E (but not of cylin D1) in transfected
      diploid cells. Whether JCV infection influences cyclin expression in a similar
      fashion in the setting of progressive multifocal leukoencephalopathy (PML)
      remains unknown. Brain lesions from 7 PML cases (4 autopsies and 3 biopsies) were
      immunohistochemically investigated for the expression of Ki-67 and cyclins A, B1,
      and D1. All 7 cases showed strong positivity for Ki-67 and cyclins A and B1 in
      JCV-infected oligodendrocytes and astrocytes, the nuclear immunolocalization of
      cyclin A being in strong contrast to the cytoplasmic distribution of cyclin B1.
      No immunostaining for cyclin D1 was obtained in any of the 7 cases. These
      findings suggest that JCV infection is associated with overexpression of Ki-67
      and cyclins A and B1 in PML host glial cells. Since cyclin changes in JCV
      infected cells recapitulate SV40 T antigen-associated cyclin fluctuations, it
      appears reasonable to think that JCV T antigen shares some of the previously
      described capabilities of SV40 T antigen to alter cyclin expression for the sake
      of viral replication.

PMID- 9600215
TI  - Selective glial vulnerability following transient global ischemia in rat brain.
AB  - Global cerebral ischemia selectively damages neurons, but its contribution to
      glial cell death is uncertain. Accordingly, adult male rats were sacrificed by
      perfusion fixation at 1, 2, 3, 5, and 14 days following 10 minutes of global
      ischemia. This insult produces CA1 hippocampal neuronal death at post-ischemic
      (PI) day 3, but minor or no damage to neurons in other regions. In situ end
      labeling (ISEL) and immunohistochemistry identified fragmented DNA of dead or
      dying glia and distinguished glial subtypes. Rare ISEL-positive oligodendroglia,
      astrocytes, and microglia were present in control brain. Apoptotic bodies and
      ISEL-positive glia significantly increased at PI day 1 in cortex and thalamus (p
      < 0.05), but were similar to controls in other regions and at other PI intervals.
      Most were oligodendroglia, although ISEL-positive microglia and astrocytes were
      also observed. These results show that oligodendroglia die rapidly after brief
      global ischemia and are more sensitive than neurons in certain brain regions.
      Their selective vulnerability to ischemia may be responsible for the delayed
      white matter damage following anoxia or CO poisoning or that associated with
      white matter arteriopathies. Glial apoptosis could contribute to the DNA ladders
      of apoptotic oligonucleosomes that have been found in post-ischemic brain.

PMID- 9600216
TI  - Necrogenesis and Fas/APO-1 (CD95) expression in primary (de novo) and secondary
      glioblastomas.
AB  - Glioblastomas may develop rapidly without clinical and histopathological evidence
      of a less malignant precursor lesion (de novo or primary glioblastoma) or through
      progression from low-grade or anaplastic astrocytoma (secondary glioblastoma).
      Primary glioblastomas typically show overexpression of EGFR, but rarely p53
      mutations, while secondary glioblastomas frequently carry a p53 mutation, but
      usually lack overexpression of EGFR, suggesting that these glioblastoma subtypes
      develop through distinct genetic pathways. In the present study, we assessed the
      expression of Fas/APO-1 (CD95), an apoptosis-mediating cell membrane protein, and
      its relation to necrosis phenotype in primary and secondary glioblastomas. Large
      areas of ischemic necroses were observed in all 18 primary glioblastomas, but
      were significantly less frequent in secondary glioblastomas (10 of 19, 53%; p =
      0.0004). Fas expression was predominantly observed in glioma cells surrounding
      large areas of necrosis and was thus significantly more frequent in primary
      glioblastomas (18 of 18, 100%) than in secondary glioblastomas (4 of 19, 21%; p <
      0.0001), suggesting that these clinically and genetically defined subtypes of
      glioblastoma differ in the extent and mechanism of necrogenesis. Necrosis and
      microvascular proliferation are histologic hallmarks of the glioblastoma.
      Following incubation of glioblastoma cell lines under hypoxic/anoxic conditions
      for 24-48 hours, Fas mRNA levels remained unchanged, whereas VEGF expression was
      markedly upregulated. This suggests that in contrast to VEGF Fas expression is
      not induced by ischemia/hypoxia. Analysis of Fas mRNA levels in a glioblastoma
      cell line containing a p53 mutation and an inducible wild-type p53 gene showed
      little difference under induced and noninduced conditions, suggesting that in
      glioblastomas, Fas expression is not directly linked to the p53 status.

PMID- 9600217
TI  - Microglia and the development of spongiform change in Creutzfeldt-Jakob disease.
AB  - Recent in vitro experiments suggest that neurotoxicity of the prion protein is
      dependent on the presence of microglia. We have studied 11 cases of Creutzfeldt
      Jakob disease (CJD) using immunocytochemistry in combination with computerized
      image analysis to clarify the relationship between spongiform change and
      microglial activation. MHC class II-positive microglia were almost exclusively
      confined to cortical gray matter where the neuropil area occupied by these cells
      exceeded that of controls more than 350-fold. In cortical regions with a bimodal
      distribution of spongiform degeneration, the presence of class II-positive
      microglia correlated well with the presence of vacuolation in layer V, but
      significantly less with spongiform change in layers II and III. In areas where
      spongiform degeneration affected the entire depth of the cortex, activated
      microglia were predominantly located in the inner one-half of the cortex or were
      evenly distributed throughout all cortical laminae. Here, microglia exhibited
      atypical, tortuous cell processes and occasionally intracytoplasmic vacuoles,
      suggesting that microglia themselves may become a disease target. Taken together,
      our results provide indirect evidence against an early causative involvement of
      microglia in the development of spongiform change. At later stages, however,
      diseased microglia could produce harmful factors which mediate both astrogliosis
      and neuronal injury.

PMID- 9600218
TI  - 4-Hydroxynonenal, a product of lipid peroxidation, damages cholinergic neurons
      and impairs visuospatial memory in rats.
AB  - The mechanisms that underlie cholinergic neuronal degeneration in Alzheimer
      disease (AD) are unclear, but recent data suggest that oxidative stress plays a
      role. We report that 4-hydroxynonenal (HNE), an aldehydic product of lipid
      peroxidation, damages and kills basal forebrain cholinergic neurons when
      administered intraparenchymally. Examination of Nissl-stained brain sections
      following unilateral HNE infusion revealed widespread neuronal loss in basal
      forebrain ipsilateral to the injection, but not on the contralateral side. Levels
      of choline acetyltransferase activity and immunoreactivity in the ipsilateral
      basal forebrain and hippocampus were significantly reduced by 60-80% seven days
      following HNE administration. Performance in Morris water maze tasks of
      visuospatial memory was severely impaired in a dose-dependent manner seven days
      following bilateral administration of HNE. Bilateral infusion of FeCl2 (an
      inducer of membrane lipid peroxidation) into the basal forebrain caused neuron
      loss and decreased choline acetyltransferease immunoreactivity and deficits in
      visuospatial memory. Additionally, FeCl2 infusion increased HNE immunoreactivity,
      implicating HNE in iron-induced oxidative damage. Because recent studies have
      demonstrated HNE adducts in degenerating neurons in AD brain, the present
      findings suggest a role for HNE in damage to cholinergic neurons in AD.

PMID- 9600220
TI  - Third ventricular chordoid glioma: a distinct clinicopathologic entity.
AB  - We have encountered a series of 8 third ventricular neoplasms with a distinctive
      chordoid appearance that appear to represent a clinicopathologic entity. The
      tumors occurred in 7 females and 1 male, ranging in age from 31 to 70 years. In
      all cases, imaging studies showed a large well-circumscribed third ventricular
      mass; a cystic component was noted in 2. The tumors consisted of cords and
      clusters of cohesive, oval-to-polygonal epithelioid cells with abundant
      eosinophilic cytoplasm, relatively uniform round-to-oval nuclei, and
      inconspicuous nucleoli. Mitotic activity was absent. The stroma consisted of
      scant, coarse fibrillar processes, as well as prominent, slightly basophilic,
      extracellular mucin resembling that in chordomas. Throughout the tumor, and
      surrounding its well-defined borders, were infiltrates of mature lymphocytes and
      plasma cells. Russell bodies were prominent in the latter. Adjacent brain tissue
      showed reactive changes with gliosis and numerous Rosenthal fibers.
      Immunohistochemically, tumor cells were strongly reactive for GFAP and vimentin,
      but negative or only weakly staining for EMA. The MIB-1 labeling index was
      approximately 1%. Ultrastructural examination of 4 cases revealed focal
      microvilli, scattered "intermediate" junctions, and focal basal lamina formation.
      Neither desmosomes nor cilia were seen. Total resections were achieved in 2
      cases; only subtotal removals were achieved in 6. Subsequent tumor enlargement
      was noted in 3 of the 6 patients with incomplete resection, and of these, two
      died at post-operative intervals of 8 months and 3 years. The other patient
      survives 4 years post-operatively with stable residual disease. Of the 2 patients
      with total resection, 1 was lost to follow-up; the other, during a brief follow
      up period, did well without evidence of recurrence.

PMID- 9600219
TI  - Abnormal iron deposition associated with lipid peroxidation in transgenic mice
      expressing interleukin-6 in the brain.
AB  - Transgenic mice, named GFAP-IL6, that express interleukin-6 in astrocytes in the
      central nervous system (CNS) have a constitutive blood-brain barrier (BBB) defect
      and develop a progressive neurodegenerative disease. Based on ultrastructural
      observations showing electron-dense pigment in the brain of the GFAP-IL6 mice, we
      hypothesized that iron metabolism was altered in the brains of these animals.
      Enhanced histochemical methods revealed abnormal iron deposition in the
      cerebellum from 1 month of age that worsened with progression of the disease.
      Immunohistochemical analysis of iron-binding proteins (IBP) showed increased
      ferritin immunoreactivity and a decreased signal from the transferrin receptor in
      symptomatic animals. Atomic absorption spectroscopy revealed a 40% increase of
      total iron concentration in the cerebellum at the symptomatic stage. In order to
      obtain evidence that accumulation of this oxidizing metal was toxic, we looked
      for the presence of oxidative damage. Using the MAL-2 antibody, extensive lipid
      peroxidation (LP) was detected in the neocortex and the cerebellum in symptomatic
      animals. Ultrastructural analysis indicated lipofuscin deposition at the sites of
      neuro-axonal degeneration and abnormal iron deposition. These results suggest
      that the IL6-induced BBB defect precipitates iron accumulation in the GFAP-IL6
      mouse brain and that subsequent IBP regulation mediates protective responses. As
      these defenses become overwhelmed, the iron overload seems to promote LP, which
      may contribute to the neurodegeneration that ensues. This transgenic mouse model
      of IL6-mediated neurodegeneration provides a unique opportunity to examine
      several aspects of iron metabolism in the brain, including its entry at the site
      of the BBB, its distribution through the IBP, and its mechanisms of toxicity.

PMID- 9600221
TI  - Prevention of experimental autoimmune neuritis by nasal administration of P2
      protein peptide 57-81.
AB  - Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated inflammatory
      demyelinating disease of the peripheral nervous system (PNS) that serves as a
      model for Guillain-Barre syndrome (GBS) in humans. Both EAN and GBS are
      associated with upregulated T and B cells responses to PNS myelin proteins
      including P2 protein, and by changes of the Th1/Th2 cell balance in favor of Th1.
      Here we report that EAN can be prevented by the dominant neuritogenic peptide 57
      81 of the PNS P2 protein when given nasally before immunization of Lewis rats
      with bovine PNS myelin (BPM) + Freund's complete adjuvant (FCA). P2 peptide
      tolerized rats were also resistant to EAN relapse after challenge with BPM.
      Tolerance to EAN in rats receiving high dose (60 microg/day/rat) P2 peptide
      nasally was associated with specific T and B cell anergy. This was characterized
      by the failure of T cells to proliferate in response to PNS myelin antigens,
      while responsiveness to phytohemagglutinin was retained. Numbers of BPM- and P2
      peptide-reactive interferon-gamma mRNA expressing lymph node cells were reduced,
      while levels of P2 peptide-reactive interleukin 4 and transforming growth factor
      beta mRNA-expressing cells were markedly upregulated on day 18 post immunization
      in the rats receiving high dose P2 peptide nasally. Tolerance to EAN was also
      associated with lower CD4+ cell infiltration, low-grade inflammation, or the
      absence of histological evidence of EAN, as well as with low IL-2 receptor and
      MHC class II molecule expression within the PNS. This is the first study showing
      that mucosal tolerance is applicable to EAN and, as an extension, could be
      considered in GBS.

PMID- 9600222
TI  - Stereology: a practical primer for neuropathology.

PMID- 9600223
TI  - POP66, a paraneoplastic encephalomyelitis-related antigen, is a marker of adult
      oligodendrocytes.
AB  - Paraneoplastic neurological diseases are disorders of the central nervous system,
      associated with neuronal degeneration in patients with systemic cancer, but are
      not a direct result of the tumor mass or metastasis. The biological diagnosis of
      these syndromes is based mainly on the detection, in the patient's serum and
      cerebrospinal fluid, of autoantibodies (anti-Hu, anti-Yo, for example),
      suggesting an autoimmune origin for these disorders. Recently, we described novel
      autoantibodies (anti-CV2 autoantibodies) associated with paraneoplastic
      neurological disease, which recognize a 66 kDa brain protein. We named this
      antigen POP66, for Paraneoplastic Oligodendrocyte Protein of 66 kDa molecular
      weight, as in the adult human, rat, and mouse brain, it is specifically expressed
      by a subpopulation of oligodendrocytes. This cell type specificity was surprising
      given the fact that the cell loss in the brains of patients with anti-CV2
      autoantibodies is neuronal. POP66-expressing oligodendrocytes are distributed
      along the longitudinal axis of the brain according to an increasing rostro-caudal
      gradient, with no positive oligodendrocytes being found in the forebrain and the
      greatest number found in the spinal cord. In addition, in transverse sections of
      the spinal cord, the distribution of POP66-positive oligodendrocytes follows an
      increasing dorsal-to-ventral gradient, which may be related to different
      oligodendrocyte precursor pools. In addition, the neuronal loss without
      demyelination seen in the brains of patients with anti-CV2 autoantibodies,
      together with the exclusive oligodendroglial expression of POP66 in the adult
      brain, raises the question of the possible involvement of POP66 in neuron
      survival via neuron/oligodendrocyte interactions.

PMID- 9600224
TI  - Progressive neuronal DNA damage associated with neurofibrillary tangle formation
      in Alzheimer disease.
AB  - DNA damage, as demonstrated by in situ Tdt-mediated dUTP-X-nick end labeling
      (TUNEL), is widespread in the cerebral cortex in end-stage Alzheimer disease, but
      has not been previously correlated with stages of neurofibrillary tangle
      formation. To assess possible relationships between neurofibrillary tangle
      formation and DNA damage, we used tau immunohistochemistry and TUNEL in tangle
      rich fields of tissue sections of subiculum and parahippocampal cortex tissue
      from 12 Alzheimer and 6 control patients. Structures were classified and
      quantified as tau-/TUNEL-, tau-/TUNEL+, tau+/TUNEL-, or tau+/TUNEL+. Tau+
      structures were subclassified into 4 stages (0-3) based on neurofibrillary tangle
      morphology. The total number of TUNEL+ neurons was significantly less in control
      than in Alzheimer patients (35 +/- 7.2 vs 90 +/- 9.3/mm2; mean +/- SEM; p <
      0.05). The number of tau+/TUNEL+ neurons (40 +/- 1/mm2) was less than that of tau
      /TUNEL- neurons (68 +/- 7/mm2) or tau-/TUNEL+ neurons in the same fields (50 +/-
      4/mm2, p < 0.0001). Tau+/TUNEL- structures were fewer in number (21 +/- 1/mm2),
      with a third of these representing acellular "ghost tangles" (stage 3). Tau+
      neurons were more likely than tau- neurons to be TUNEL+ (64 +/- 6% vs 44 +/- 2%;
      mean +/- SEM; p < 0.01), although most TUNEL+ neurons were tau-, even in these
      selected, tangle-rich fields. TUNEL positivity was not uniformly distributed
      among tangle stages. TUNEL positivity was less common among early (stage 0)
      tangles than in tau neurons (21 +/- 6% vs 44 +/- 2%; p < 0.001), but this rose to
      53% among intermediate (stage 1) tangles, and to 87% among late (stage 2)
      tangles. We suggest that early stages of neurofibrillary tangle formation occur
      in a subpopulation of relatively healthy (TUNEL-) neurons, and that tangle
      progression is accompanied by increasing neuronal morbidity.

PMID- 9600225
TI  - Loss of cholinergic synapses on the spinal motor neurons of amyotrophic lateral
      sclerosis.
AB  - The expression of vesicular acetylcholine transporter (VAChT) was examined
      immunohistochemically in the cholinergic synapses on the spinal motor neuron of
      the patient with sporadic amyotrophic lateral sclerosis (SALS). VAChT
      immunoreactive synapses were depleted on surviving motor neurons in SALS, while
      synaptophysin immunoreactivity was undiminished on the same neurons. This
      discrepancy suggests that in SALS, loss of cholinergic input on lower motor
      neurons is an early event, and may be part of the cause of death of those motor
      neurons.

PMID- 9600226
TI  - Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson's
      disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity.
AB  - A mutation in the alpha-synuclein gene has recently been linked to some cases of
      familial Parkinson's disease (PD). We characterized the expression of this
      presynaptic protein in the midbrain, striatum, and temporal cortex of control,
      PD, and dementia with Lewy bodies (DLB) brain. Control brain showed punctate
      pericellular immunostaining. PD brain demonstrated alpha-synuclein
      immunoreactivity in nigral Lewy bodies, pale bodies and abnormal neurites. Rare
      neuronal soma in PD brain were immunoreactive for alpha-synuclein. DLB cases
      demonstrated these findings as well as alpha-synuclein immunoreactivity in
      cortical Lewy bodies and CA2-3 neurites. These results suggest that, even in
      sporadic cases, there is an early and direct role for alpha-synuclein in the
      pathogenesis of PD and the neuropathologically related disorder DLB.

PMID- 9600227
TI  - Protein nitration in Parkinson's disease.
AB  - Oxidative stress has been proposed as a pathogenetic mechanism in Parkinson's
      disease (PD). One mechanism of oxidative cellular injury is the nitration of
      protein tyrosine residues, mediated by peroxynitrite, a reaction product of
      nitric oxide and superoxide radicals. We demonstrate here the presence of
      nitrotyrosine immunoreactivity in Lewy bodies within melanized neurons and in
      amorphous deposits associated with intact and degenerating neurons. The core of
      the Lewy body was frequently intensely immunolabeled, while the rim was lightly
      labeled or unlabeled. This likely reflects the fact that tyrosine residues of
      neurofilament proteins are primarily localized to Lewy body cores, and suggests
      that nitrotyrosine is present in neurofilament protein itself. Although these
      observations are as yet unable to provide a definitive link between oxidative
      stress and neuronal dysfunction, they demonstrate that oxidative stress has
      occurred within the vulnerable neurons of PD, leaving a permanent marker of
      oxidative modification of neuronal proteins within the target cells of
      neurodegeneration. In addition, these observations provide a potential link
      between excitotoxicity and oxidative stress within the vulnerable neurons of PD
      and represent a pathogenetic mechanism in common with the 2 other major age
      related neurodegenerative diseases, Alzheimer disease and amyotrophic lateral
      sclerosis.

PMID- 9600228
TI  - Amyloid beta-protein (A beta) accumulation in the putamen and mammillary body
      during aging and in Alzheimer disease.
AB  - Immunocytochemical studies clearly showed that amyloid beta-protein (A beta)
      deposits are widely distributed in the subcortical regions as well as the
      cortices of normal aged and Alzheimer disease (AD) brains. To investigate the
      temporal profile of A beta accumulation in the subcortical region, we quantitated
      A beta40 and A beta42 levels, using sensitive enzyme immunoassays, in the putamen
      and mammillary bodies of normal individuals aged 24 to 87 years and of AD
      patients. In these two regions, A beta42 was the predominant species; in
      particular, A beta42 was the only A beta species detected in the putamen. In
      several cases the mammillary body contained only A beta40, but not A beta42.
      Although the extent of A beta accumulation in the 2 subcortical regions was much
      less than that in the cortex of the same subject, A beta42 appears to accumulate
      in both subcortical regions at the same time as in the cortex and leptomeninges.
      In addition, the A beta42 levels in the putamen or in the mammillary body
      correlated with those in the occipitotemporal cortex. This strongly suggests that
      the extent of A beta42 accumulation in the brain is determined not only by the
      duration of A beta accumulation but also by other unknown regional factors.
      Western blotting showed that the initial A beta species to accumulate in the
      putamen or mammillary body varied among individuals. In some cases, an A beta42
      stable dimer was the most predominant species, while in other cases a 3 or 4 kD A
      beta42 monomer was more abundant, suggesting that the clearance rates of the A
      beta42 stable dimer and monomer are different in vivo.

PMID- 9600229
TI  - Progression of cerebral amyloid angiopathy: accumulation of amyloid-beta40 in
      affected vessels.
AB  - Cerebrovascular deposits of amyloid (cerebral amyloid angiopathy, or CAA) are
      generally asymptomatic, but in advanced cases, they can lead to vessel rupture
      and hemorrhage. The process of progression in CAA was studied by comparison of
      postmortem brains with asymptomatic ("mild") CAA to brains with the form of the
      disease associated with hemorrhage ("severe CAA"). Cortical and meningeal vessels
      were immunostained for beta-amyloid and examined by confocal microscopy and by
      systematic quantitative sampling. We focused on 2 quantitative parameters: the
      proportion of vessels affected by amyloid (a measure of amyloid seeding of
      vessels) and the amount of amyloid per affected vessel (a measure of growth of
      existing lesions). Surprisingly, there was no difference between the proportion
      of affected cortical vessels in mild and severe CAA (0.29 vs 0.32, p = 0.65), but
      rather an increase in the area of the 40 amino acid form of beta-amyloid per
      affected cortical vessel (198.5 +/- 38.7 vs 455.8 +/- 100.9 microm2/vessel, p <
      0.007). Increasing doses (from 0 to 1 to 2 copies) of the apolipoprotein E
      epsilon4 allele were also associated with greater amyloid per vessel without
      change in the proportion of affected vessels within each class of CAA severity.
      These findings suggest that progression from asymptomatic to advanced CAA
      reflects progressive accumulation of amyloid in vessels previously seeded with
      amyloid, and that this process is selectively enhanced by apolipoprotein E
      epsilon4.

PMID- 9600230
TI  - Shrinkage of motor axons following systemic exposure to inorganic mercury.
AB  - Systemically-administered inorganic mercury localizes to motor neurons, but it is
      not known if mercury injures these neurons. We therefore looked for signs of
      damage to the motor and sensory neurons of mice that had been exposed to
      inorganic mercury. Young adult mice were injected intraperitoneally with either 1
      or 2 microg/g of mercuric chloride and perfused 1 or 30 weeks later. The cellular
      distribution of mercury in the spinal cord was examined with silver nitrate
      autometallography. The numbers and sizes of myelinated axons in the L5 anterior
      and posterior roots were quantitated using an image analysis program. Mercury was
      found throughout the cytoplasm of motor neuron cell bodies after 1 week and in
      paranuclear aggregations after 30 weeks. Thirty weeks after exposure to either 1
      or 2 microg/g of mercury, fewer large myelinated axons were seen in mercury
      injected groups than in controls, though total numbers of myelinated axons did
      not differ between groups. A slight increase in numbers of small axons was seen
      in the posterior roots of mice exposed to 1 microg/g of mercury. In conclusion,
      inorganic mercury remains within mouse neurons for prolonged periods and causes a
      reduction in the size of myelinated axons in the anterior root and to a lesser
      extent the posterior spinal root. Inorganic mercury within motor neurons
      therefore appears to behave as a slowly-acting neurotoxin that shrinks motor
      axons.

PMID- 9600231
TI  - Germ line mosaicism.
AB  - Mosaicism in germ cells has been recognized, over the past few years, as an
      important and relatively frequent mechanism at the origin of genetic disorders.
      There are two possibilities for the existence of such a mosaicism: one is that
      the mutation occurs in a germ cell that continues to divide. The other
      possibility is that the mutation occurs very early in a somatic cell before the
      separation to germinal cells and is therefore present both in somatic and
      germinal cells. Depending on various factors, such as the gene involved and/or
      the degree of mosaicism, the carrier of a somatic and germline mosaicism may be
      asymptomatic or may present with various symptoms of the disease. There are still
      relatively few reports in the literature in which the origin of germ-line
      mosaicism has been analyzed; nevertheless, they allow for a better insight into
      the mechanisms involved. In some diseases, such as osteogenesis imperfecta, new
      mutations are often present as asymptomatic somatic and germline mosaicism in one
      of the parents of the propositus. In other disorders, such as neurofibromatosis,
      somatic mosaicism is very rare in the parents of the propositus, perhaps since
      such mosaicism causes clinical symptoms. These differences are particularly
      important for genetic counseling in order to evaluate the risk for another
      affected child after the birth of the propositus.

PMID- 9600233
TI  - Analysis of HLA-DQ alpha sequences for prenatal diagnosis in single fetal cells
      from maternal blood.
AB  - We have extended a previously developed method that allows prenatal DNA diagnosis
      of female fetuses through the isolation of single nucleated erythrocytes from
      maternal blood by developing a method that can distinguish between maternal and
      fetal nucleated erythrocytes. Nucleated erythrocytes were separated by a density
      gradient method and then collected by micromanipulation. Sex was determined after
      primer extension preamplification (PEP) of the entire genome of a single cell,
      and human leukocyte antigen (HLA)-DQ alpha type was determined after further
      amplification of this gene. The HLA-DQ alpha genotype of fetal erythrocytes in
      maternal blood samples and their corresponding paternal and maternal lymphocytes
      were successfully determined in all cases. The accuracy of the method was
      determined by using single nucleated erythrocytes from umbilical cord blood from
      five normal deliveries. This is the first demonstration that the fetal HLA-DQ
      alpha gene sequences can be identified in a small aliquot of a single nucleated
      erythrocyte in maternal blood. We believe that this method ushers in a new era in
      which the reliability and accuracy of noninvasive prenatal DNA diagnosis from
      maternal blood is markedly improved.

PMID- 9600232
TI  - Analysis of the human Sonic Hedgehog coding and promoter regions in sacral
      agenesis, triphalangeal thumb, and mirror polydactyly.
AB  - The human Sonic Hedgehog gene (SHH) is one of the vertebrate homologs related to
      the Drosophila segment polarity gene hedgehog. The entire coding and promoter
      region of the SHH gene, including 2 kb 5' of the transcriptional start site has
      been screened for mutations in families with autosomal dominant sacral agenesis
      and autosomal dominant triphalangeal thumb, two conditions previously known to be
      linked to 7q36. We have also studied the SHH gene in five families with mirror
      polydactyly associated with tibial hemimelia and in 51 unrelated patients with
      neural tube defects. Except for two sequence variants in exon 3, no mutations
      were found in these disease categories. OFF

PMID- 9600234
TI  - Telomeric length and telomerase activity vary with age in peripheral blood cells
      obtained from normal individuals.
AB  - The telomerase activity and length of telomeres of peripheral blood mononuclear
      cells obtained from 124 healthy individuals aged 4-95 years was measured.
      Telomerase activity level was semiquantitatively assessed by a fluorescent
      telomeric repeat amplification protocol (fluorescent-TRAP) using an internal
      telomerase assay standard, fluorescent primers and an automated laser fluorescent
      DNA sequencer. Telomeric length, measured by assay of terminal restriction
      fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis
      using a (TTAGGG)4 probe. TRF length was determined in 80 individuals and age
      related progressive reduction of size was observed. TRF length in peripheral
      blood mononuclear cells obtained from normal individuals (aged 4-39 years)
      decreased by approximately 84 bp per year, while in individuals aged > or = 40
      years it decreased by 41 bp per year. In contrast, telomerase activity showed an
      apparent biphasic pattern with aging. Individuals aged 4-39 years showed a
      progressive decrease in telomerase activity, whereas 65% of those aged > or = 40
      years showed relatively stable but very low telomerase activity, and the
      remaining individuals aged > or = 40 years had no detectable telomerase activity.
      These data obtained from normal individuals might in the future be of value to
      help risk stratify and manage the care of patients with leukemia.

PMID- 9600235
TI  - Mutations of the ATM gene detected in Japanese ataxia-telangiectasia patients:
      possible preponderance of the two founder mutations 4612del165 and 7883del5.
AB  - The ATM (A-T, mutated) gene on human chromosome 11q22.3 has recently been
      identified as the gene responsible for the human recessive disease ataxia
      telangiectasia (A-T). In order to define the types of disease-causing ATM
      mutations in Japanese A-T patients as well as to look for possible mutational
      hotspots, reverse-transcribed RNA derived from ten patients belonging to eight
      unrelated Japanese A-T families was analyzed for mutations by the restriction
      endonuclease fingerprinting method. As has been reported by others, mutations
      that lead to exon skipping or premature protein truncation were also predominant
      in our mutants. Six different mutations were identified on 12 of the 16 alleles
      examined. Four were deletions involving a loss of a single exon: exon 7, exon 16,
      exon 33 or exon 35. The others were minute deletions, 4649delA in exon 33 and
      7883del5 in exon 55. The mutations 4612del165 and 7883del5 were found in more
      than two unrelated families; 44% (7 of 16) of the mutant alleles had one of the
      two mutations. The 4612del165 mutations in three different families were all
      ascribed to the same T-->A substitution at the splice donor site in intron 33.
      Microsatellite genotyping around the ATM locus also indicated that a common
      haplotype was shared by the mutant alleles in both mutations. This suggests that
      these two founder mutations may be predominant among Japanese ATM mutant alleles.

PMID- 9600236
TI  - Common fragile sites on human chromosomes represent transcriptionally active
      regions: evidence from camptothecin.
AB  - Cellular processes involved in the expression of fragile sites (FS) have been
      investigated by studying the possible modulation of their induction by
      camptothecin, a specific topoisomerase I inhibitor. Expression of FS was induced
      by aphidicolin and then camptothecin was administered to cultures during G2
      phase. Under these conditions, a very high number of chromosome aberrations were
      obtained: R-bands carrying FS were specifically involved in breakage and, in
      particular, the common FS (cFS) bands already expressed in aphidicolin-treated
      cultures were the most affected. These data show that the expressed FS are
      preferential targets of camptothecin, that is, regions where topoisomerase I
      cleavable complexes are formed. This allows us to hypothesize that cFS could
      represent the cytogenetic expression of transcriptionally active regions. These
      treatments were able to induce, besides the known FS, four new FS, namely 1p34,
      6p21, 6q25, and 15q15.

PMID- 9600237
TI  - Interplay between humans and infective agents: a population genetic study.
AB  - The genetic composition of present day human populations is determined largely by
      the interaction between the human host and infective agents. Therefore,
      theoretical analysis of the host-infective-agent system is required in order for
      us to be able to understand human evolution. Classical population genetics has
      been confined largely to analysing the interplay of various mechanisms, such as
      selection, mutation and drift, in one species at a time. Unfortunately, there
      have been few studies of such interactive systems. In the present investigation,
      these studies have been enlarged, with problems of human genetics in mind, by
      mathematical examination of a model in which a diploid host with three alleles
      interacts with a haploid infective agent with two alleles. The results are
      compared with those obtained from simpler models analysed in the past. The
      assumptions inherent in such "gene for gene" models and our results are
      discussed. An increase in the number of alleles appears to enhance the chances
      for the establishment of permanent genetic polymorphisms, improving genetic
      "elasticity" of a population for coping with changing challenges by various
      infective agents. Interaction between two haploid species leads to a loss of
      polymorphism in both of them and, hence, to a severe loss of evolutionary
      elasticity. The hypothesis that the evolution of diploidy might have been
      favoured by a selective advantage of diploid organisms interacting with
      environmental challenges, such as infective agents, is supported.

PMID- 9600238
TI  - Variability of biochemical and clinical phenotype in X-linked liver glycogenosis
      with mutations in the phosphorylase kinase PHKA2 gene.
AB  - X-linked liver glycogenosis (XLG) resulting from phosphorylase kinase (Phk)
      deficiency is one of the most common forms of glycogen storage disease. It is
      caused by mutations in the gene encoding the liver isoform of the Phk alpha
      subunit (PHKA2). In the present study, we address the issue of phenotypic and
      allelic heterogeneity in XLG. We have identified mutations in seven male
      patients. One of these patients represents the variant biochemical phenotype, XLG
      subtype 2 (XLG2), where Phk activity is low in liver but normal or even elevated
      in erythrocytes. He carries a K189E missense mutation, which adds to the emerging
      evidence that XLG2 is associated with missense mutations clustering at a few
      sites. Two patients display clinical phenotypes unusual for liver Phk deficiency,
      with dysfunction of the kidneys (proximal renal tubular acidosis) or of the
      nervous system (seizures, delayed cognitive and speech abilities, peripheral
      sensory neuropathy), respectively, in addition to liver glycogenosis. In the
      patient with kidney involvement, we have identified a missense mutation (P399S)
      and a trinucleotide deletion (2858del3) leading to the replacement of two amino
      acids by one new residue (N953/L954I), and a missense mutation has also been
      found in the patient with neurological symptoms (G1207W). These two cases
      demonstrate that PHKA2 mutations can also be associated with uncommon clinical
      phenotypes. Finally, in four typical XLG cases, we have identified three
      truncating mutations (70insT, R352X, 567del22) and an in-frame deletion of eight
      well-conserved amino acids (2452del24). Together, this study adds eight new
      mutations to the previously known complement of sixteen PHKA2 mutations. All
      known PHKA2 mutations but one are distinct, indicating pronounced allelic
      heterogeneity of X-linked liver glycogenosis with mutations in the PHKA2 gene.

PMID- 9600239
TI  - A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab
      kindred with nonketotic hyperglycinemia.
AB  - Nonketotic hyperglycinemia (NKH) is caused by a mutation in the genes encoding
      the components of the glycine cleavage multi-enzyme system. More than 80% of the
      patients have defects in the gene encoding P-protein, whereas the rest of the
      patients have defects in the gene encoding T-protein. We have found a large
      Israeli-Arab kindred with NKH. At least 14 children were affected, and all the
      patients had seizures and respiratory failure within 2 days after birth.
      Enzymatic analysis revealed that T-protein activity was deficient in the liver
      specimen from one propositus. We screened this family for a mutation in the
      protein-coding region and exon/intron boundaries of T-protein gene by direct
      sequencing analysis. A missense mutation was found in exon 2; this resulted in an
      amino acid substitution from histidine to arginine at position 42 (H42R).
      Histidine 42 is conserved in human, bovine, chicken, pea, and Escherichia coli,
      suggesting that it has an important role in catalytic functions. Genotype
      analyses of 26 family members confirmed that the homozygous H42R mutation was
      completely associated with the onset of NKH. The availability of DNA testing
      facilitates the prenatal diagnosis of NKH and the identification of carriers,
      which is necessary for genetic counseling in the affected families.

PMID- 9600240
TI  - Genomic organization and mutational analysis of HERG, a gene responsible for
      familial long QT syndrome.
AB  - Familial long QT syndrome (LQTS) is characterized by prolonged ventricular
      repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden
      death may occur as a result of ventricular tachyarrhythmias. Three genes
      responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so
      far, and mutations have been reported on the basis of partially characterized
      genomic organization. To optimize the search for HERG mutations, we have
      determined the genomic structure of HERG and investigated mutations in LQTS
      families. Human genomic clones containing the HERG gene were isolated from a
      human genomic library by using reverse-transcribed polymerase chain reaction (RT
      PCR) products from this gene as probes. We determined exon/intron boundaries and
      flanking intronic sequences by using primers synthesized on the basis of the HERG
      cDNA sequence available in the DNA database. HERG was shown to consist of 15
      exons spanning approximately 19 kb on chromosome 7q35. Subsequently, we
      synthesized oligonucleotide primers to cover the entire coding region and
      searched for mutations in 36 Japanese LQTS families. When genomic DNA from each
      proband was examined by the PCR/single-strand conformation polymorphism technique
      followed by direct DNA sequencing, five novel mutations were detected. Each
      mutation was present in affected relatives of the respective proband. This work
      should increase the efficiency of screening mutations associated with HERG.

PMID- 9600241
TI  - Mutational analysis of the FMR1 gene in 118 mentally retarded males suspected of
      fragile X syndrome: absence of prevalent mutations.
AB  - Fragile X syndrome is usually caused by expansion of a trinucleotide (CGG) repeat
      in the 5'-untranslated region of the FMR1 gene. However, both deletions and point
      mutations in FMR1 have been identified as rare causes of the fragile X syndrome.
      We have screened the FMR1 gene for mutations by single-stranded conformational
      polymorphism analysis in 118 mentally retarded males who were referred to us for
      fragile X testing, and who had a CGG repeat number in the normal size range. We
      found one patient with a 2-bp deletion in intron 1 and two unrelated patients
      with identical silent mutations in exon 1. Neither of these mutations were found
      in 83 controls. Further investigation of the exon 1 silent mutation by Western
      blot analysis showed normal expression of FMRP in lymphoblastoid cells and
      reverse-transcription-polymerase chain reaction analysis showed that intron 1 and
      2 were spliced out as in the normal control. Furthermore, we found two common
      polymorphisms, one in intron 1 and one in exon 5. However, no pathogenic FMR1
      mutation was found.

PMID- 9600242
TI  - Molecular analysis of the chromosomal equipment in spermatozoa of a 46, XY,
      t(7;8) (q11.21;cen) carrier by using fluorescence in situ hybridization.
AB  - The meiotic segregation of a balanced reciprocal translocation (7;8) (q11.21;cen)
      was analysed by interphase fluorescence in situ hybridization (FISH) on carrier
      spermatozoa. A dual interphase FISH technique was applied to 34,527 decondensed
      sperm heads with chromosome-7- and chromosome-8-specific alpha-satellite probes.
      Analysis with such probes was possible according to the cytogenetic
      characteristics of these translocation breakpoints, which implied a centromeric
      breakpoint. The majority of the analysed nuclei (56.70%) showed normal (30.40%)
      or balanced (26.30%) chromosomal equipment resulting from alternate segregation
      during meiosis. A total of 14,935 spermatozoa (43.26%) was unbalanced with a
      predominance of gametes resulting from adjacent-I (25.10%) or adjacent-II
      (11.10%) segregation; such gametes could produce partial mono- or trisomies at
      term. The frequency of analysed cells resulting from a 3:1 segregation, which
      could induce complete mono- and trisomies at term, was 7.06%; 0.04% of scored
      cells were diploid. The same dual-FISH technique was carried out either with
      chromosome-15- and chromosome-18-specific probes or with gonosome-specific
      probes, in order to detect a possible interchromosomal effect. A significant
      increase of disomic 18 spermatozoa was observed in the carrier. Such studies are
      not yet frequent. Multicolour-FISH seems a rapid and accurate tool for direct
      analyses of spermatogenetic segregation mechanisms in a carrier of balanced
      chromosomal abnormalities and provides interesting information for characterizing
      the possible risks for the offspring.

PMID- 9600243
TI  - The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and of 13
      novel mutations causing glutaric aciduria type I.
AB  - Glutaric acidemia type I (GAI) (McKusick 231670) is an autosomal recessive
      disease affecting the catabolism of the amino acids lysine, hydroxylysine and
      tryptophan, caused by a defect in the gene encoding glutaryl-coenzyme A
      dehydrogenase (GCDH) and associated with severe neurological symptoms. Several
      pathogenic mutations in GCDH have been reported to cause GAI. One mutation,
      R402W, is more common than the others, which seem to be private" mutations. Here
      we report the entire sequences of introns 1, 2, 3, 6, 7, 8 and 9, and part of
      those of introns 4, 5 and 10 as well as 21 different mutations in 20 patients
      with GAI, corresponding to 38 out of 40 alleles.

PMID- 9600244
TI  - Molecular genetic characterization of two metachromatic leukodystrophy patients
      who carry the T799G mutation and show different phenotypes; description of a
      novel null-type mutation.
AB  - Metachromatic leukodystrophy (MLD) is an autosomal recessive storage disease
      caused by deficiency of the lysosomal enzyme, arylsulfatase A. Two common
      mutations causing MLD have been characterized and correlations between phenotype
      and genotype have been established. A third common mutation, T799G, has also been
      identified in European MLD patients, and is associated with the late-onset forms
      of the disease. We report the molecular analysis of two Italian MLD patients,
      with juvenile and adult onset of the disease, respectively, who carried the T799G
      mutation in compound heterozygosity with different null mutations. A novel rapid
      mutation detection method is demonstrated for patient screening. One patient has
      a novel mutation, a T553C [corrected] transition that results in the substitution
      of Pro for Leu at codon 135, and produces no enzymatic activity in transfection
      experiments.

PMID- 9600245
TI  - Three novel KCNA1 mutations in episodic ataxia type I families.
AB  - Hereditary paroxysmal ataxia, or episodic ataxia (EA), is a rare, genetically
      heterogeneous neurological disorder characterized by attacks of generalized
      ataxia. By direct sequence analysis, a different missense mutation of the
      potassium channel gene (KCNA1) has been identified in three families with EA.

PMID- 9600246
TI  - The genetic basis of Cowden's syndrome: three novel mutations in PTEN/MMAC1/TEP1.
AB  - Cowden's syndrome (CS) is an autosomal dominant disorder associated with an
      increased risk of developing benign and malignant tumors in a variety of tissues,
      including the skin, thyroid, breast and brain. Women with CS are felt to have an
      increased risk of developing breast cancer, and virtually all women with CS
      develop bilateral fibrocystic disease of the breast. Recently, a series of
      germline mutations have been identified from CS families in a gene known as
      PTEN/MMAC1/TEP1. In this study, we used heteroduplex analysis and direct
      sequencing analysis and identified three novel germline mutations in the
      PTEN/MMAC1/TEP1 coding sequence from unrelated individuals with CS. We report a
      de novo transition (T-->C) at nucleotide 335 in exon 5. This missense mutation
      resulted in a leucine to proline (CTA to CCA) change at codon 112. We also
      describe a novel splice site mutation (801+2T-->G) in intron 7 that caused exon
      skipping in PTEN/MMAC1/TEP1 mRNA. The third mutation we report is a missense
      mutation, consisting of a transition (T-->C) at nucleotide 202 in exon 3,
      resulting in a tyrosine to histidine (TAC to CAC) change at codon 68. Finally, we
      also detected a rare polymorphism in exon 7 of the PTEN/MMAC1/TEP1 coding
      sequence. These data confirm the observation that mutations of the
      PTEN/MMAC1/TEP1 coding sequence are responsible for at least some cases of CS,
      and further define the spectrum of mutations in this autosomal dominant disorder.

PMID- 9600247
TI  - Mutational analysis of the GDNF/RET-GDNFR alpha signaling complex in a kindred
      with vesicoureteral reflux.
AB  - Glial cell line-derived neurotrophic factor (GDNF) mediates signaling across the
      cell membrane by interaction with the RET-GDNFR alpha receptor complex. We
      identified a family in which one member had medullary thyroid carcinoma (MTC) and
      four members had vesicoureteral reflux (VUR). Knowledge that mutations in the RET
      proto-oncogene cause MTC and studies documenting genitourinary abnormalities in
      RET or GDNF knockout mice led us to examine the GDNF/RET-GDNFR alpha signaling
      complex in this family. RET and GDNF were excluded as the causative VUR gene by
      haplotype and sequence analysis. The GDNFR alpha gene was mapped to chromosome
      10q25-26 by radiation hybrid techniques and was eliminated as the causative gene
      by haplotype analysis and sequencing of cDNA from an obligate carrier. Sequencing
      identified a 15-nucleotide deletion in GDNFR alpha mRNA, which was found to code
      for a single exon; analysis of several cell types revealed an identical mRNA
      form, indicating that this variant is a product of alternative RNA processing. We
      conclude that GDNFR alpha maps to 10q25-26 and that its RNA transcript is
      alternatively processed. Mutation abnormalities in the GDNF/RET-GDNFR alpha
      signaling system do not cause VUR in this family.

PMID- 9600248
TI  - High frequency of polymorphism but no mutations found in the GLUT1 glucose
      transporter gene in NIDDM and familial obesity by SSCP analysis.
AB  - To evaluate whether a structural defect in the human glucose transporter gene
      GLUT1 could be involved in the aetiology of insulin resistance, a key factor of
      non-insulin-dependent diabetes mellitus (NIDDM) and obesity, we performed single
      strand conformation polymorphism (SSCP) analysis in 40 subjects (20 NIDDM
      patients and 20 subjects with familial obesity). The GLUT1 gene, which is
      involved in basal glucose transport in most tissues, consists of ten exons and
      encodes a 492 amino acid protein. Population studies have shown a strong
      association between the X1 allele of an XbaI restriction fragment length
      polymorphism of the GLUT1 gene and NIDDM. We therefore performed SSCP analysis in
      NIDDM subjects known to carry at least one X1 allele. Variant SSCP patterns were
      detected in exons 2, 4, 5 and 9. Sequence analysis of the SSCP variants revealed
      the presence, in all exons examined, of silent mutations consisting of single
      nucleotide substitutions with no amino acid changes. Both NIDDM and obese
      patients showed a high frequency of polymorphism in the sequence (50% and 35%,
      respectively). We conclude that the GLUT1 gene is unlikely to play a role in the
      aetiology of NIDDM and obesity. However, the strong association between the GLUT1
      gene and NIDDM, together with the recent family studies showing linkage between
      chromosome 1p and NIDDM warrant further studies on this chromosomal region.

PMID- 9600249
TI  - Mutational analysis of the CCR5 and CXCR4 genes (HIV-1 co-receptors) in
      resistance to HIV-1 infection and AIDS development among intravenous drug users.
AB  - We analysed a group of Spanish intravenous drug users and controls to determine
      the role of mutations at the chemokine receptor-5/HIV-1 cofactor (CCR5),
      previously implicated in resistance to HIV-1 infection, and CXCR4 genes in
      susceptibility to HIV-1 infection. The complete coding sequence of both genes was
      amplified by the polymerase chain reaction from genomic DNA of 50 seropositive
      slow progressors and 10 long-term non-progressors, and analysed by the single
      strand conformation polymorphism technique in a search for mutations. No mutation
      in CXCR4 was found, and delta ccr5 was the only mutation identified at the CCR5
      gene. We genotyped (delta ccr5 allele) 150 HIV-1+ intravenous drug users and 250
      healthy controls from the same population (Asturias, Northern Spain). Patients
      were divided into rapid progressors, presenting an event indicating progression
      to the acquired immunodeficiency syndrome (AIDS) in the 2 years after infection
      (100 patients), and slow progressors, remaining asymptomatic for 2-10 years (50
      patients). The frequencies of the delta ccr5 allele were 0.105 and 0.040 in
      controls and HIV-1+ patients, respectively. Eighteen per cent of the controls
      (45/250) and 8% (12/150) of the patients carried the delta ccr-5 allele
      (P=0.013). The frequency of delta ccr5 carriers among rapid and slow disease
      progressors was 3 and 15%, respectively. A highly significant difference was
      found between rapid progressors and controls (P=0.0014). No patient (0/150) was
      delta ccr5 homozygous compared with 1% among controls. Thus, the delta ccr5
      allele (the only CCR5 mutation found in our HIV-1 patients) was rare among
      seropositive intravenous drug users, suggesting that the absence of this mutation
      confers an advantage to the virus when infecting cells in vivo. In addition,
      patients carrying the delta ccr5 allele tend to show a slow progression towards
      HIV-1-related disease, remaining asymptomatic for longer periods of time.

PMID- 9600250
TI  - UBE3A "mutations" in two unrelated and phenotypically different Angelman syndrome
      patients.
AB  - Angelman syndrome (AS) is a rare neurodevelopmental disorder. Recently, several
      mutations have been found in the E6-AP ubiquitin protein ligase gene (UBE3A) in a
      group of patients who are nondeleted and do not have uniparental disomy or
      imprinting defects. Most of the reported mutations cluster within exons 9 or 16
      of the UBE3A gene, and nearly all are predicted to give rise to truncated E6-AP
      ligases. Here, we describe two AS patients with dissimilar phenotypes. At the
      molecular level, they are both nondeleted, do not display uniparental disomy, and
      have normal imprint patterns. One has the typical AS phenotype and carries the
      previously reported 1344delAG de novo mutation involving a functionally
      significant region of UBE3A. The other expresses an atypical phenotype in that
      she has less severe ataxia, no inappropriate laughing, or epilepsy, and her EEG
      was normal at an early age. A 14-bp deletion in the 3' untranslated region of
      exon 16 (3'UTRdel14) adjacent to the poly(A) signal was identified. Further
      investigation revealed that the DNA change was a neutral polymorphism. Haplotype
      analysis indicated that both the AS patient and her normal sibling had inherited
      the same maternal UBE3A gene and its 5' flanking region. Although the 14-bp
      change has no functional significance, it assists with counseling to determine
      future risks of recurrence in this family.

PMID- 9600251
TI  - Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18
      reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q.
AB  - Linkage analysis was performed on a large Danish family to refine the position of
      RP18, the locus for autosomal dominant retinitis pigmentosa, mapped previously
      between D1S534 and D1S305 in chromosome 1p13-q21. We genotyped the family members
      for five microsatellite-type DNA polymorphisms and mapped RP18 between D1S422 and
      D1S2858 to a region of less than 2 cM. No obvious candidate gene has yet been
      assigned to the chromosomal interval defined here.

PMID- 9600252
TI  - Gene symbol: COL11A1. Disease: Marshall syndrome.

PMID- 9600253
TI  - Prion protein structural features indicate possible relations to signal
      peptidases.
AB  - Transmissible spongiform encephalopathies (TSEs) in mammalian species are
      believed to be caused by an oligomeric isoform, PrP(Sc), of the cellular prion
      protein, PrP(C). One of the key questions in TSE research is how the observed
      accumulation of PrP(Sc), or possibly the concomitant depletion of PrP(C) can
      cause fatal brain damage. Elucidation of the so far unknown function of PrP(C) is
      therefore of crucial importance. PrP(C) is a membrane-anchored cell surface
      protein that possesses a so far unique three-dimensional structure. While the N
      terminal segment 23-120 of PrP(C) is flexibly disordered, its C-terminal residues
      121-231 form a globular domain with three alpha-helices and a two-stranded beta
      sheet. Here we report the observation of structural similarities between the
      domain of PrP(121-231) and the soluble domains of membrane-anchored signal
      peptidases. At the level of the primary structure we find 23% identity and 41%
      similarity between residues 121-217 of the C-terminal domain of murine PrP and a
      catalytic domain of the rat signal peptidase. The invariant PrP residues Tyr-128
      and His-177 align with the two presumed active-site residues of signal peptidases
      and are in close spatial proximity in the three-dimensional structure of PrP(121
      231).

PMID- 9600255
TI  - Three-stepped rotation of subunits gamma and epsilon in single molecules of F
      ATPase as revealed by polarized, confocal fluorometry.
AB  - The proton translocating ATP synthase is conceived as a rotatory molecular
      engine. ATP hydrolysis by its headpiece, CF1, drives the rotation of subunit
      gamma relative to the hexagonally arranged large subunits, (alphabeta)3. We
      investigated transition states of the rotatory drive by polarized confocal
      fluorometry (POCOF) as applied to single molecules of engineered, immobilized and
      load-free spinach-CF1. We found that the hydrolysis of ATP caused the stepped and
      sequential progression of subunit gamma through three discrete angular positions,
      with the transition states of gamma being too shortlived for detection. We also
      observed the stepped motion of epsilon, whereas delta was immobile as
      (alphabeta)3.

PMID- 9600254
TI  - The isolated H4-H5 cytoplasmic loop of Na,K-ATPase overexpressed in Escherichia
      coli retains its ability to bind ATP.
AB  - The H4-H5 loop of the alpha-subunit of mouse brain Na,K-ATPase was expressed and
      isolated from Escherichia coli cells. Using fluorescence analogues of ATP, this
      loop was shown to retain its capability to bind ATP. Isolation of a soluble H4-H5
      loop with the native ATP binding site is a crucial step for detailed studies of
      the molecular mechanism of ATP binding and utilisation.

PMID- 9600256
TI  - Pattern of methionine adenosyltransferase isoenzyme expression during rat liver
      regeneration after partial hepatectomy.
AB  - The present report investigates the pattern of expression of liver-specific and
      extrahepatic methionine adenosyltransferase (MAT) isoenzymes in regenerating rat
      liver after partial hepatectomy. The results show that there is a switch in the
      expression of these isoenzymes that is coincident with maximal cell proliferation
      in the remaining liver lobes. Extrahepatic MAT levels increase about three times
      4 h after hepatectomy, reaching a maximum 36 h later. This is accompanied by a
      rapid and transient increase in total MAT activity and levels of related
      metabolites S-adenosyl-L-methionine and S-adenosyl-L-homocysteine. Liver-specific
      MAT levels are reversibly down-regulated within 24-48 h post surgery. Our results
      indicate that MAT isoenzyme expression is tightly regulated during liver
      regeneration after two-third hepatectomy. The implications of these observations
      for evaluation of the degree of liver regeneration are briefly discussed.

PMID- 9600257
TI  - Site-directed mutagenesis and chemical modification of the two cysteine residues
      of the UDP-N-acetylmuramoyl:L-alanine ligase of Escherichia coli.
AB  - Site-directed mutagenesis and chemical modification of the two cysteine residues
      of the MurC L-alanine-adding enzyme from Escherichia coli were undertaken to
      study their possible role in activity and stability. Their replacement by alanine
      was not critical for activity. However, C230 played a role in enzyme stability
      and substrate binding. N-Ethylmaleimide alkylation led to monoalkylated and
      dialkylated proteins. The monoalkylated protein had mostly unmodified C230
      residues. The extent of alkylation of C230 paralleled the loss of activity,
      whereas that of C426 did not. Protection against inactivation by beta,gamma
      imidoadenosine 5'-triphosphate implied the involvement of C230 in the ATP binding
      site.

PMID- 9600258
TI  - Direct formation of mixed micelles in the solubilization of phospholipid
      liposomes by Triton X-100.
AB  - The vesicle to micelle transition which results in the interaction of the Triton
      X-100 surfactant with phosphatidylcholine vesicles was studied by means of
      dynamic light scattering (at different reading angles) and by freeze-fracture
      electron microscopy techniques. Vesicle solubilization was produced by the direct
      formation of mixed micelles without the formation of complex intermediate
      aggregates. Thus, vesicle to micelle transformation was mainly governed by the
      progressive formation of mixed micelles within the bilayer. A subsequent
      separation of these micelles from the liposome surface (vesicle perforation by
      the formation of surfactant-stabilized holes on the vesicle surface) led to a
      complete solubilization of liposomes.

PMID- 9600259
TI  - Analogs of farnesylcysteine induce apoptosis in HL-60 cells.
AB  - S-Farnesyl-thioacetic acid (FTA), a competitive inhibitor of isoprenylated
      protein methyltransferase, potently suppressed the growth of HL-60 cells and
      induced apoptosis, as evidenced by the development of increased annexin-V
      binding, decreased binding of DNA dyes and internucleosomal DNA degradation. FTA
      did not impair the membrane association of ras proteins, conversely, it brought
      about a decrease in the proportion of ras present in the cytosolic fraction.
      Farnesylated molecules which are weak inhibitors of the methyltransferase also
      induced DNA laddering and reduced the proportion of cytosolic ras. These findings
      suggest that neither inhibition of isoprenylated protein methylation nor
      impairment of ras membrane association are essential for apoptosis induced by
      farnesylcysteine analogs.

PMID- 9600260
TI  - Proton exchange kinetics in [d(ACGTATACGT)]2-echinomycin and [d(ACGTTAACGT)]2
      echinomycin complexes.
AB  - Based on imino proton exchange catalysis, base-pair lifetimes and apparent
      dissociation constants are reported on the complexes formed by bisintercalation
      of echinomycin at the CpG steps of the d(ACGTATACGT)2 and d(ACGTTAACGT)2
      duplexes. The lifetimes of the four central A x T base pairs between two
      echinomycin binding sites are much shorter than in the free duplexes. The
      destabilization of base pairs adjacent to the binding sites is propagated one
      additional base pair away from the binding site.

PMID- 9600261
TI  - Quercetin is recovered in human plasma as conjugated derivatives which retain
      antioxidant properties.
AB  - Quercetin is one of the most abundant flavonoids in the human diet. This study
      aimed to determine the plasma concentrations of quercetin in 10 healthy
      volunteers after the consumption of a complex meal rich in plant products.
      Quercetin was determined in plasma (2 h before, and 3, 7 and 20 h after the
      meal), and in a duplicated portion of the meal by HPLC analysis with an
      electrochemical detection. The amount of ingested quercetin was estimated to be
      87 mg. Before the meal, quercetin concentration in hydrolyzed plasmas ranged from
      28 to 142 nM. A marked increase was observed 3 h after the meal in all subjects,
      with a mean concentration of 373 nM (S.E.M. = 61). After 7 h, quercetin
      concentration in hydrolyzed plasmas decreased and after 20 h basal levels were
      found again. The antioxidant capacities of quercetin, 3'-O-methylquercetin, and
      of some of their conjugated derivatives were compared by the measurement of the
      conjugated dienes resulting from the Cu2+-induced oxidation of human LDL. 3'-O
      Methylquercetin and conjugated derivatives of quercetin significantly prolonged
      the lag phase, but the magnitude of their effect was about half that of the
      aglycone.

PMID- 9600262
TI  - Ectopic expression of lunatic Fringe leads to downregulation of Serrate-1 in the
      developing chick neural tube; analysis using in ovo electroporation transfection
      technique.
AB  - Lunatic Fringe (l-Fng) is one of the vertebrate homologues of Drosophila Fringe,
      which interacts with the Notch signal pathway and regulates activation of the
      Notch ligands, Delta and Serrate. To elucidate the roles of l-Fng in vertebrate
      neurogenesis, we transfected chick l-Fng (C-l-Fng) to chick neural tube using the
      in ovo electroporation technique and examined the subsequent changes in
      expression of Notch-related genes. We observed downregulation of C-Serrate-1 by
      ectopic C-l-Fng expression which implied that C-l-Fng acts on the vertebrate
      Notch pathway to regulate the expression of its ligand.

PMID- 9600263
TI  - Lovastatin and sodium phenylacetate normalize the levels of very long chain fatty
      acids in skin fibroblasts of X- adrenoleukodystrophy.
AB  - The present study underlines the importance of lovastatin, an inhibitor of 3
      hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, and the sodium salt of
      phenylacetic acid (NaPA), an inhibitor of mevalonate pyrophosphate decarboxylase,
      in normalizing the pathognomonic accumulation of saturated very long chain fatty
      acids (VLCFA) in cultured skin fibroblasts of X-adrenoleukodystrophy (X-ALD) in
      which the ALD gene is either mutated or deleted. Lovastatin or NaPA alone or in
      combination stimulated the beta-oxidation of lignoceric acid (C24:0) and
      normalized the elevated levels of VLCFA in skin fibroblasts of X-ALD. Ability of
      lovastatin and NaPA to normalize the pathognomonic accumulation of VLCFA in skin
      fibroblasts of X-ALD may identify these drugs as possible therapeutics for X-ALD.

PMID- 9600264
TI  - Secondary structure and thermal stability of the extrinsic 23 kDa protein of
      photosystem II studied by Fourier transform infrared spectroscopy.
AB  - The secondary structure and thermal stability of the extrinsic 23 kDa protein
      (OEC23) of spinach photosystem II have been characterized in solution between 25
      and 75 degrees C using Fourier transform infrared spectroscopy. Quantitative
      analysis of the amide I band (1700-1600 cm(-1)) shows that OEC23 contains 5%
      alpha-helix, 37% beta-sheet, 24% turn, and 34% disorder structures at 25 degrees
      C. No appreciable conformational changes occur below 45 degrees C. At elevated
      temperatures, the beta-sheet structure is unfolded into the disorder structure
      with a major conformational transition occurring at 55 degrees C. Implications of
      these results for the functions of OEC23 in photosystem II are discussed.

PMID- 9600265
TI  - Composition of parental mitochondrial DNA in cloned bovine embryos.
AB  - We have investigated parental mitochondrial DNA (mtDNA) in cloned bovine embryos
      obtained by intraspecific cytoplast-blastomere fusion. Analysis of two-cell to
      blastocyst stage embryos revealed that in contrast to the exclusion of paternal
      (sperm) mtDNA during sexual inheritance in the cytoplast-blastomere fusion
      complexes, there was mixing and co-existence of parental mtDNA. The mixing of
      mtDNA was non-balanced with the minority deriving from the blastomere. The
      constant content of mtDNA during embryogenesis until the blastocyst stage
      suggesting an absence of mtDNA replication was shown for conventional 'in vitro
      fertilised' (IVF) embryos and for cloned embryos. The ratio of parental mtDNA was
      in accordance with the estimated quantitative participation of mtDNA from the
      fusion partners.

PMID- 9600266
TI  - Non-balanced mix of mitochondrial DNA in cloned cattle produced by cytoplast
      blastomere fusion.
AB  - We have investigated the transmission of parental mitochondrial DNA (mtDNA) in
      three clones of born cattle obtained by intraspecific cytoplast-blastomere
      fusion. Using allele-specific TaqMan PCR a low level transmission of blastomere
      mtDNA (DB mtDNA) into the cloned offspring was detected, thereby generating a
      heteroplasmic population of mtDNA. The amount of DB mtDNA was 13% and 18% in two
      animals of a clone which derived from a 24-cell morula and 0.6% and 0.4% in two
      calves of clonal origin derived from a 92-cell morula. These values are in
      accordance with the tendency expected for neutral mtDNA segregation that the
      fewer cell divisions that have occurred in the donor embryo, the higher the
      amount of DB mtDNA. We also found a strong decrease of DB mtDNA which was about
      three orders of magnitude in the third clone derived from a 52-cell morula stage.

PMID- 9600267
TI  - Retinoids, omega-hydroxyfatty acids and cytotoxic aldehydes as physiological
      substrates, and H2-receptor antagonists as pharmacological inhibitors, of human
      class IV alcohol dehydrogenase.
AB  - Kinetic constants of human class IV alcohol dehydrogenase (sigmasigma-ADH)
      support a role of the enzyme in retinoid metabolism, fatty acid omega-oxidation,
      and elimination of cytotoxic aldehydes produced by lipid peroxidation. Class IV
      is the human ADH form most efficient in the reduction of 4-hydroxynonenal
      (k(cat)/Km: 39,500 mM(-1) min(-1)). Class IV shows high activity with all-trans
      retinol and 9-cis-retinol, while 13-cis-retinol is not a substrate but an
      inhibitor. Both all-trans-retinoic and 13-cis-retinoic acids are potent
      competitive inhibitors of retinol oxidation (Ki: 3-10 microM) which can be a
      basis for the regulation of the retinoic acid generation and of the
      pharmacological actions of the 13-cis-isomer. The inhibition of class IV retinol
      oxidation by ethanol (Ki: 6-10 mM) may be the origin of toxic and teratogenic
      effects of ethanol. H2-receptor antagonists are poor inhibitors of human and rat
      classes I and IV (Ki > 0.3 mM) suggesting a small interference in ethanol
      metabolism at the pharmacological doses of these common drugs.

PMID- 9600268
TI  - Importance of the N-glycan in the V3 loop of HIV-1 envelope protein for CXCR-4-
      but not CCR-5-dependent fusion.
AB  - The V3 region of HIV-1 envelope protein possesses a single N-linked sugar chain,
      which is conserved in most HIV-1 strains. We studied its role in the life cycle
      of HIV-1 strains with different co-receptor usage. Removal of the glycan appeared
      to cause a marked reduction of CXCR-4- but not CCR-5-dependent virus entry. A
      basic amino acid substitution at the 11th position of V3 markedly compensated for
      the removal of the N-glycan. These results indicate that the N-glycan plays an
      important role for CXCR-4-dependent virus entry and that this role is exerted in
      a particular context of the peptide backbone.

PMID- 9600269
TI  - Endogenous tumour necrosis factor-alpha sensitise melanoma cells to
      glucosaminylmuramyl dipeptide.
AB  - Flow cytometry was used to demonstrate that cultured human melanoma BRO cells
      expressed membrane-bound tumour necrosis factor-alpha (TNF-alpha) and were able
      to release TNF-alpha upon treatment with glucosaminylmuramyl dipeptide (GMDP).
      The released TNF-alpha was shown to prime melanoma cells, previously unable to
      respond to GMDP by increasing expression of melanoma-associated antigens, making
      them sensitive to GMDP treatment.

PMID- 9600270
TI  - Inhibition and enhancement of odorant-induced cAMP accumulation in rat olfactory
      cilia by antibodies directed against G alpha S/olf- and G alpha i-protein
      subunits.
AB  - The odorant-induced accumulation of cAMP can be inhibited by antibodies directed
      against G alpha s/olf. In contrast, antibodies raised against G alpha i-subunits
      caused a strong enhancement of the odorant-induced cAMP accumulation. Western
      blotting and immunoelectron microscopy revealed the presence of both G alpha
      s/olf- and G alpha i-subunits in rat cilia preparations. The existence of both
      stimulatory and inhibitory odorant-induced regulation of adenylyl cyclase
      activity in olfactory cilia may indicate that an initial integration of different
      odorant stimuli begins at the level of primary reactions in the same effector
      enzyme.

PMID- 9600271
TI  - Insulin receptor-deficient cells as a new tool for dissecting complex interplay
      in insulin and insulin-like growth factors.
AB  - Cell systems derived from knockout mice for the insulin receptor (IR) or the IGF
      1 receptor (IGF-1R) represent unique tools for dissecting complex interplay in
      the actions of insulin and insulin-like growth factors through their cognate
      versus non-cognate receptor. In this study, we used a fibroblast cell line
      derived from IR-deficient mice to investigate metabolic and mitogenic effects of
      IGF-1 and insulin. IGF-1 was able to stimulate glucose uptake, glucose
      incorporation into glycogen and thymidine incorporation in such cells.
      Phosphatidylinositol 3-kinase and mitogen-activated protein kinase, two enzymes
      of major metabolic-mitogenic signaling pathways, were activated upon stimulating
      these cells with IGF-1. All these effects were also achieved when IR-deficient
      cells were stimulated with insulin. Thus, IGF-1R can represent an alternative
      receptor through which insulin might exert some of its effects.

PMID- 9600272
TI  - Association of beta 1 integrin with protein kinase activity in large detergent
      resistant complexes.
AB  - Integrins play a critical role in cell adhesion and mediate cell signaling. This
      report identifies the association of serine protein kinase activity with the beta
      1 integrin by immunoprecipitation and phosphoamino acid analysis techniques.
      Reprecipitation techniques suggested that the serine kinase activity was not a
      member of the protein kinase C family. By gel filtration, most of the protein
      kinase activity associated with beta 1 integrin as well as most of the cell
      surface beta 1 integrin was present in large detergent resistant complexes. These
      results suggest that serine protein kinase activity associated with the beta 1
      integrin may play a role in signaling via the beta 1 integrin.

PMID- 9600273
TI  - Reactivity of beta-carotene towards peroxyl radicals studied by laser flash and
      steady-state photolysis.
AB  - Peroxyl radicals, as model for peroxyl radicals formed during autoxidation of
      lipids, have been generated in three solvent systems (cyclohexane,
      tetrahydrofuran and tert-butanol/water) by steady-state and laser flash
      photolysis, and their reaction with beta-carotene studied. Steady-state
      photolysis experiments showed that alkyl, alkoxyl and alkylperoxyl radicals all
      react with beta-carotene. However, laser flash photolysis experiments indicated
      that the reaction with peroxyl radicals (second-order rate constant estimated to
      be less than 10(6) M(-1) s(-1)) is slower than with alkyl and alkoxyl radicals,
      and that beta-carotene is hence a poor direct scavenger of peroxyl radicals.
      Scavenging of peroxyl radicals by beta-carotene is suggested not to proceed via
      electron transfer but rather by adduct formation and/or hydrogen abstraction. For
      different phenoxyl radicals, differences in reactivity towards beta-carotene seem
      to be correlated with standard reduction potential.

PMID- 9600274
TI  - Xanthine oxidoreductase is asymmetrically localised on the outer surface of human
      endothelial and epithelial cells in culture.
AB  - Subcellular localisation of xanthine oxidoreductase (XOR) was determined by
      indirect immunofluorescence using confocal microscopy in human endothelial and
      epithelial cell lines and in primary cultures of human umbilical vein endothelial
      cells. XOR was diffusely distributed throughout the cytoplasm but with higher
      intensity in the perinuclear region. In non-permeabilised cells, XOR was clearly
      seen to be asymmetrically located on the outer surfaces, showing, in many cases,
      a higher intensity on those faces apposed by closely neighbouring cells. Such
      specific distribution suggests a functional role for the enzyme in cell-cell
      interactions, possibly involving signalling via reactive oxygen species.

PMID- 9600275
TI  - Outcomes analysis in 100 liver transplantation patients.
AB  - BACKGROUND: There is an increasing demand for outcomes analysis, including
      quality of life and financial analysis, following medical interventions and
      surgical procedures. We analyzed outcomes for 100 consecutive patients undergoing
      liver transplantation during a period of case management revision. METHODS:
      Patient survival was calculated by Kaplan-Meier actuarial methods. The Karnofsky
      performance status was objectively assessed for surviving patients up to 6 years
      after transplantation and was evaluated by repeated measures analysis of variance
      and covariance. Subjective evaluation of quality of life over time was obtained
      using the Psychosocial Adjustment to Illness Scale. The correlations between time
      and scale were calculated. Financial data were accumulated from billing records.
      RESULTS: Six-month, 1-year, 2-year, and 3- through 5-year survival was 86%, 84%,
      83%, and 78%, respectively. Karnofsky performance status confirmed poor
      functional status preoperatively with a mean of 53 +/- 2, but significantly
      improving to 72 +/- 2 at 3 months, 80 +/- 2 at 6 months, 90 +/- 1 at 1 year, 92
      +/- 1 at 2 years, 94 +/- 1 at 3 years, 96 +/- 1 at 4 years, and 97 +/- 1 at 5
      years (P <0.001). Psychosocial Adjustment to Illness Scale scores demonstrated
      significant improvement following transplantation overall (r = -0.33), improving
      most in sexual relationships (r = -0.41), and domestic environment (r = -0.35; P
      <0.001). Median length of stay for the first half of the patients was 19 days
      declining to 11 days for the second half. Median hospital charges declined from
      $105,000 to $90,000. CONCLUSIONS: Quality of life parameters assessed both by
      care givers (Karnofsky) and by patients (Psychosocial Adjustment to Illness
      Scale) improved dramatically following transplantation and over time,
      demonstrating that liver transplantation effectively restores a good quality of
      life. Outcomes can be improved while reducing length of stay and charges through
      modifications in case management.

PMID- 9600276
TI  - Hepatic allograft abscess with hepatic arterial thrombosis.
AB  - BACKGROUND: Intrahepatic abscess (IA) is an uncommon complication after liver
      transplantation (OLTx) usually found in the setting of hepatic arterial
      thrombosis (HAT) often with associated biliary tree necrosis and/or stricture.
      Conventional treatment of IA in this setting has required retransplantation.
      METHODS: A retrospective review of 274 patients (287 OLTx) from September 1991
      through September 1996 was performed. Median follow-up was 3.6 years. Diagnosis
      of HAT was confirmed by arteriography and IA was documented by computerized
      tomography. Percutaneous drainage of the abscess and stenting of biliary
      strictures, if present, was achieved using conventional interventional radiology
      techniques. RESULTS: The diagnosis of hepatic artery complication was made in 14
      patients (5.1%), 2 of whom required retransplantation. Hepatic artery thrombosis
      associated with solitary IA was found in 3 patients (1%) who were transplanted in
      our center and in 1 additional patient followed up at our center but transplanted
      elsewhere. All 4 patients had complete resolution of IA using this approach.
      Three of the 4 patients are alive and well, with the fourth patient succumbing to
      recurrent hepatitis B infection resulting in allograft failure. CONCLUSIONS:
      Solitary hepatic allograft abscesses associated with HAT respond to percutaneous
      drainage and antibiotics, obviating the need for retransplantation in this
      setting.

PMID- 9600277
TI  - Transanal local excision of selected low rectal cancers.
AB  - BACKGROUND: To determine if transanal local excision (TALE) of selected early low
      rectal cancer is an effective alternative to more radical resection and to
      determine the need for adjuvant radiotherapy in these patients. METHODS: A
      retrospective analysis of all 47 cases referred for consideration of radiotherapy
      after TALE for low rectal cancer. RESULTS: Indications for TALE were elective,
      32; concurrent medical problems, 11; and refusal of radical resection, 4. Median
      follow-up was 52 months. Local recurrence occurred in 7 of 27 T1 cases, 5 of 17
      T2, and 2 of 3 T3. Three of 23 irradiated patients developed local recurrence,
      compared with 11 of 24 unirradiated (P = 0.023). Of 28 cases with favorable
      histological features, 1 of 13 irradiated patients developed local recurrence,
      compared with 4 of 16 unirradiated (P = 0.22). Seven patients had salvage
      resection, and 3 of these are alive with no evidence of disease at 21, 39, and 71
      months postsalvage. Recurrence-free survival at 5 years was 81 % in the
      irradiated patients and 52% in the unirradiated (P = 0.025). CONCLUSIONS:
      Transanal local excision of selected low rectal cancers, combined with adjuvant
      radiotherapy, results in a low recurrence rate and is, therefore, an effective
      alternative to more radical resection.

PMID- 9600278
TI  - The association between telomerase, p53, and clinical staging in colorectal
      cancer.
AB  - BACKGROUND: A proposed etiology of tumor activation involves p53 mutations while
      telomerase may serve as a key enzyme for maintenance of tumor cell proliferation.
      METHODS: Telomerase activity levels were measured in colorectal adenocarcinomas
      and corresponding normal tissue using a modified telomeric repeat amplification
      protocol, and p53 mutations were identified using immunohistochemical staining.
      Results were compared with staging data using regression analysis. RESULTS:
      Telomerase activity was present in 23 of 23 (100%) of the tumors and only 2 (9%)
      of normal specimens (P <0.0001). The p53 mutations were present in 18 of 23 (78%)
      of the tumors. No significant correlation between p53 mutations, telomerase
      activity levels, and staging was found. CONCLUSIONS: Telomerase activity in 100%
      of the tumors suggests telomerase activation is a universal event in colorectal
      tumor progression; however, telomerase activity appears to be independent of p53
      mutations and clinical staging.

PMID- 9600279
TI  - Resectional gastric bypass is a new alternative in morbid obesity.
AB  - BACKGROUND: Severe obesity is a common serious health problem in the United
      States. Medical therapy is often ineffective. A variety of surgical procedures
      have been employed for treatment of morbid obesity. Surgical therapy continues to
      evolve. METHODS: Eighty-five patients have undergone subtotal gastrectomy and
      retrocolic Roux-en-Y gastrojejunostomy for weight control at our institution. We
      refer to this procedure as resectional gastric bypass (RGB). Thirty-eight
      patients have undergone RGB as conversion from failed or problematic prior
      bariatric procedures. Forty-seven patients have had RGB as their primary
      bariatric procedure. RESULTS: Twenty-six patients undergoing RGB for conversion
      of an anatomically or functionally failed prior bariatric procedure have had mean
      additional weight loss of 37% excess body weight (EBWL) in 18 months follow-up.
      Twelve patients undergoing RGB for intractable side effects of prior bariatric
      procedures have all had clinical improvement. Forty-seven patients undergoing RGB
      as a primary procedure have had EBWL of 53%, in mean follow-up of 11 months. For
      the entire series, major complications were one anastomotic leak, one
      reexploration for suspected subphrenic abscess, and one major pulmonary embolus.
      These patients recovered. There was no mortality in the series. CONCLUSIONS:
      Resectional gastric bypass is a new alternative for salvage of a failed or
      problematic prior bariatric procedure. It is also effective as a primary weight
      control operation.

PMID- 9600280
TI  - Comparison of outcomes of open versus laparoscopic Nissen fundoplication
      performed in a single practice.
AB  - BACKGROUND: We reviewed Nissen fundoplications performed in a single practice
      from January 1989 to March 1997, encompassing our transition from open to
      laparoscopic procedures. Because all operations were done by two surgeons in the
      same two hospitals, the study is well controlled for comparisons. METHODS:
      Records of 271 consecutive patients were reviewed. RESULTS: From 1989 to 1992 all
      patients underwent open fundoplication (n = 78). Thereafter, with increasing
      frequency, laparoscopic fundoplication was performed. The laparoscopic group was
      slightly younger (48 +/- 14 years) than the open group (54 +/- 13 years), but
      gender distribution and body mass index (BMI) did not differ. Mean operating time
      for laparoscopic cases was 163 +/- 58 minutes compared with 148 +/- 59 minutes
      for open cases (NS). Intraoperative complication rate was 8% for both groups.
      Length of hospitalization was shorter for patients undergoing laparoscopic
      surgery (2.4 days versus 7.2 for open procedures, P <0.05). In follow-up, 82% of
      the open Nissen group were asymptomatic compared with 84% of the laparoscopic
      Nissen group. The same proportion of patients required reoperation for dysphagia
      (3% for each group). Of patients who had the open procedure, 21% had wound
      complications. None of those treated laparoscopically had long-term morbidity
      from trocar insertion sites. CONCLUSION: Equal effectiveness in treating reflux
      combined with shorter hospitalization and absence of wound complications makes
      the laparoscopic approach the preferred method for performing fundoplication.

PMID- 9600281
TI  - Unusual abscess patterns following dropped gallstones during laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy has become the standard treatment for
      symptomatic cholelithiasis. Numerous clinical trials have deemed it a safe
      procedure, regardless of the known increased risk of bile duct injury. However,
      the consequences and incidence of less well-known complications are still being
      addressed. METHODS: Between 1993 and 1995, 1,130 laparoscopic cholecystectomies
      were performed at two major metropolitan medical centers. Of these patients, we
      know of 3 (0.3%) who subsequently developed abscesses as a consequence of dropped
      stones during the laparoscopic cholecystectomy. One additional patient who
      underwent prior laparoscopic cholecystectomy at another institution developed
      late infection as well. RESULTS: All 4 patients developed late purulent abscesses
      that ultimately required open surgical drainage, and 1 patient developed trocar
      site "tumor" masses that were secondary to inflammatory tissue around gallstone
      fragments. All patients were successfully treated by surgical drainage, stone
      removal, and antibiotics. Trocar site inflammatory masses required excision only.
      Significant costs were involved in the diagnosis, management, and duration of
      therapy for these problems. CONCLUSIONS: This experience closely resembles that
      of other centers and points out the existence of a late postoperative
      complication following laparoscopic cholecystectomy that was rarely encountered
      with open cholecystectomy. Strategies for avoiding this problem are discussed.
      Whether dropped stones are an indication for conversion to open cholecystectomy
      remains unclear. Thorough irrigation at time of laparoscopic cholecystectomy with
      or without placement of a drain in the subhepatic space does not prevent this
      complication.

PMID- 9600282
TI  - Accuracy of stereotactic core-needle breast biopsy in atypical ductal
      hyperplasia.
AB  - BACKGROUND: The histologic diagnosis of atypical ductal hyperplasia (ADH) has
      been reported as having a high rate of malignancy, either ductal carcinoma in
      situ (DCIS) or invasive ductal carcinoma (IDC). We reviewed our surgical group's
      experience with stereotactic core-needle biopsies (SCNB), specifically looking at
      the follow-up of ADH. METHODS: From November 1994 through July 1997 our group
      performed 539 SCNB. Twenty-one patients (4%) were diagnosed as ADH. Eighteen
      patients had subsequent wire-localized excisional biopsies. Three patients were
      followed up mammographically. One patient refused follow-up. RESULTS: Of the 18
      patients who underwent excisional biopsies, 2 patients were found to have DCIS
      and 1 patient had lobular carcinoma in-situ. There were no cases of IDC.
      CONCLUSION: Our results show a much lower incidence of malignancy in cases of ADH
      found on SCNB than has been previously reported. While the standard of care is
      still to follow up ADH found on SCNB with excisional biopsy, more data may
      justify following up certain subsets of patients.

PMID- 9600283
TI  - Accurate and cost-effective evaluation of breast masses in males.
AB  - BACKGROUND: Because the majority of breast masses in males are benign and need
      not be excised if asymptomatic, we studied the combination of physical
      examination (PE) and fine needle aspiration (FNA), with or without mammography,
      as a diagnostic alternative to routine surgical biopsy of these lesions. METHODS:
      A diagnostic test study and cost-effectiveness analysis was performed in three
      participating multidisciplinary breast clinics, involving a consecutive sample of
      51 males with unilateral breast masses. Each lesion was tested with both PE and
      FNA; 13 were also studied with mammography, and each test was scored as benign or
      suspicious. Lesions for which all tests were benign were followed up clinically
      (mean 19 months). Lesions for which any test was suspicious were excised.
      RESULTS: All tests were benign in 38 cases. No cancers developed at the index
      sites during follow-up of these lesions, including 8 excisional biopsies done for
      symptoms (negative predictive value and specificity 100%). Open biopsy confirmed
      malignancy in all 6 cases for which all tests were suspicious (positive
      predictive value and sensitivity 100%). In all 7 cases where the tests were not
      in agreement, open biopsy was benign. In these cases FNA (2 false positives)
      proved more accurate than PE (5 false positives). Mammography added no additional
      diagnostic information to the combination of PE and FNA. Compared with routine
      open biopsy, the combination of PE and FNA avoided surgical biopsy in 30 of the
      51 lesions, and was associated with an average decrease in charges of up to $510
      per case. CONCLUSIONS: The combination of PE and FNA for the evaluation of breast
      masses in males is diagnostically accurate and results in a reduction in patient
      charges compared with routine open biopsy.

PMID- 9600284
TI  - Predictors of outcome of forefoot surgery for ulceration and gangrene.
AB  - BACKGROUND: Surprisingly little is known about the long-term outcome of forefoot
      surgery for limb salvage. METHODS: From January 1, 1992 through December 31,
      1996, patients requiring toe amputation or forefoot surgery were prospectively
      entered into a computerized database and followed up for healing, need for repeat
      foot surgery, or major amputation (below or above knee). RESULTS: A total of 162
      patients (mean age 65 years), 72% diabetic, 10% with end-stage renal disease
      (ESRD), and 73% without palpable pulses, were entered into the study. Mean follow
      up was 25 months. Of patients without palpable pulses (n = 98), 83% underwent
      concomitant or subsequent limb revascularization. Eleven of 98 revascularization
      procedures (11%) were hemodynamically unsuccessful. Nonhealing of the initial
      forefoot procedure occurred in 14%, and late repeat foot surgery (following
      initial healing) was required in an additional 14%. Major amputation was
      eventually required in 30 (18.5%) patients. Multivariate analysis indicated that
      unsuccessful revascularization, but not diabetes or ESRD, predicted nonhealing
      and major amputation (P <0.0001). Patients presenting with palpable pulses and
      neuropathic ulcers were at risk for late, repeat foot surgery, but not major
      amputation (P = 0.0015). CONCLUSIONS: In patients requiring toe or partial
      forefoot amputation, success of revascularization is the primary predictor of
      initial healing and freedom from major amputation. Neuropathic ulceration
      predicts need for repeat foot surgery following healing.

PMID- 9600285
TI  - Operative outcomes of minimally invasive saphenous vein harvest.
AB  - BACKGROUND: The longest incision used in surgery is the standard incision for
      harvesting the greater saphenous vein for arterial grafting. This long incision
      is associated with significant pain and morbidity. We present a comparative study
      between two relatively less invasive techniques: the standard bridge technique
      (BT) and the endoscopic saphenous vein harvest (ESVH). PATIENTS AND METHODS: This
      is a prospective, nonrandomized, case-matched study of contemporaneous minimally
      invasive saphenous vein harvest in patients undergoing multiple vessel coronary
      artery bypass grafting (CABG). Data points include operative time, total wound
      length, length of vein harvested, intraoperative complications, conversions to
      open, injury to the graft, postoperative complications and hospital length of
      stay. Follow-up continued for 8 weeks postdischarge. RESULTS: Within a 10-month
      period (July 1996 to May 1997), 60 saphenous vein harvests were performed, with
      29 by BT and 31 by ESVH. Patient demographics were well matched, except for a
      larger number of patients with peripheral vascular disease in the ESVH group.
      ESVH only required 2.3 incisions versus 5 for the BT (P = 0.000001), whereas ESVH
      produced on average longer veins of 53.9 cm versus 47.7 cm for BT (P = 0.05).
      Harvest times were comparable in the two groups. However, mean vein preparation
      times, incision closure times, and total vein operative times for the BT were,
      respectively, 18.5 minutes, 35.1 minutes, and 94 minutes versus significantly
      less times of 11.3 minutes (P = 0.009), 10.6 minutes (P = 0.000001), and 73
      minutes (P = 0.0001), respectively, for ESVH. The early, minor wound complication
      rate was 32% for the ESVH group versus 3% for the BT group (P = 0.0048). However,
      excluding small wound hematomas, the wound complication rate in the ESVH group
      fell to 13%. Graft quality was acceptable in both groups. CONCLUSIONS: ESVH was
      demonstrated to be a useful procedure to harvest saphenous veins for CABG
      surgery. The ESVH technique allowed the harvesting of a longer vein, via shorter
      and fewer incisions and in less time. However, for maximum operating room
      efficiency with the new technology, staff education is essential. There was a
      greater incidence of minor wound complications in the ESVH group; however, the
      majority of these ESVH complications were small wound hematomas, which did not
      occur as surgeon experience with the technique increased.

PMID- 9600286
TI  - Surgical treatment of infected aortic aneurysm.
AB  - BACKGROUND: We report results of infected aortic aneurysms treated by a single
      group over 20 years. METHODS: Retrospective review. RESULTS: Seventeen patients
      were treated, 10 with infrarenal and 7 suprarenal infections. All had
      abdominal/back pain, 88% were febrile, 71% had leukocytosis, and 24% were
      hemodynamically unstable. The most common responsible organism was Staphylococcus
      aureus (29%) followed by Salmonella organisms (24%). All suprarenal infections
      were gram-positive organisms. Infrarenal infections were treated with preliminary
      axillofemoral bypass followed by aortic resection. Suprarenal infections were
      treated with either in situ prosthetic graft or patch repairs. Operative survival
      was 90% for infrarenal and 57% for suprarenal infections. Operative deaths
      occurred in the setting of overwhelming sepsis and/or severe preoperative
      hemodynamic instability. There was no limb loss, renal failure, or intestinal
      ischemia. Late deaths occurred in 4 patients at 1.3 to 6.3 years postoperatively
      and were unrelated to their aortic repairs. Nine patients remain alive with a
      median follow-up of 2 years. There have been no late aortic or graft infections.
      CONCLUSIONS: In the absence of hemodynamic instability and uncontrolled sepsis,
      infected aortic aneurysms can be successfully repaired with durable results.

PMID- 9600287
TI  - Incidence of abdominal wall hernia in aortic surgery.
AB  - BACKGROUND: True aneurysms of the abdominal aorta and its branches are at least
      in part due to defects in the structural integrity of the arterial wall. Whether
      the defect is isolated to the vascular wall is unclear. If the structural
      weakness involves other tissues, patients with aneurysmal disease should have a
      higher incidence of collagen and fascial defects, such as abdominal and inguinal
      hernias. METHOD: We reviewed 100 patients who underwent elective aortic
      reconstruction for aneurysmal or occlusive disease. All patients were operated on
      by the same group of vascular surgeons, through a midline incision, with fascia
      closed using running absorbable suture. Midline incisional and inguinal hernias
      were identified, and all patients were followed up for at least 1 year.
      Comparisons between groups were made for established risk factors for ventral
      hernias. RESULTS: Incisional hernias occurred in 18 of 58 (31%) aneurysm
      patients, compared with 5 of 42 (12%) occlusive disease patients (P = 0.025).
      Inguinal hernias occurred in 11 of 58 (19%) aneurysm patients versus 2 of 42 (5%)
      occlusive disease patients (P = 0.037). Risk factors were equally distributed
      between the two groups. Neither the size of the aneurysm nor the presence of an
      iliac artery aneurysm affected the incidence of abdominal wall hernias in the
      aneurysm patients. CONCLUSION: This study emphasizes the increased incidence of
      abdominal wall hernias in patients undergoing aortic surgery for aneurysm disease
      compared with aortoiliac occlusive disease. The size of the aneurysm and the
      association of an iliac artery aneurysm did not affect the incidence of hernias
      among these patients. Genetic and biochemical abnormalities are considered as
      possible explanations.

PMID- 9600288
TI  - Recent trends in diagnosis and treatment of Clostridium difficile in a tertiary
      care facility.
AB  - BACKGROUND: With the prevalence of antibiotic use, the diagnosis and management
      of Clostridium difficile disease requires assessment. METHODS: In a retrospective
      review, patients with a positive culture, toxin, or both during 1 year were
      identified. Recent literature was reviewed. Results of culture and toxin, prior
      antibiotic use, antibiotic treatment history and cost were analyzed. RESULTS: Of
      592 patients tested, 101 were positive; 96 of 101 were available for review. Of
      those positive tested for both, 45% were positive for toxin and culture. Sixty
      two of 96 were treated with antibiotics; metronidazole was used in 90%. Ten of 62
      antibiotic treatments were changed (mean 3 days). Ten days of metronidazole is
      1/200th the cost of vancomycin. CONCLUSIONS: In 55% of the positive cases in
      which culture and toxin were obtained, one test was negative. As metronidazole's
      efficacy and cost compares favorably with vancomycin, metronidazole is the drug
      of choice. Any changes made to antibiotic regimens occurred prior to the 6 days
      recommended in the literature.

PMID- 9600289
TI  - Hepatic artery chemoembolization for management of patients with advanced
      metastatic carcinoid tumors.
AB  - BACKGROUND: Patients with advanced metastatic carcinoid tumors who have disease
      progression despite conventional therapy are left with few therapeutic options.
      Hepatic artery chemoembolization (HACE) may play a role in palliating these
      patients' symptoms. METHODS: Fifteen patients with biopsy-proven advanced bilobar
      hepatic carcinoid metastases who demonstrated progression of symptoms and/or
      tumor size despite treatment with somatostatin analogues were treated with intra
      arterial chemotherapy and HACE to determine efficacy and safety. Five days of
      intra-arterial 5-fluorouracil (1 g/m2) were followed by HACE with adriamycin (60
      mg), cisplatin (100 mg), mitomycin C (30 mg), and polyvinyl alcohol (Ivalon); 200
      micron to 710 micron). Patients were continued on octreotide at the same dose
      (150 to 2000 microg subcutaneous q 8 hours) before, during, and after the
      procedure. RESULTS: Efficacy of treatment was assessed by comparing pretreatment
      and 3-month clinical, laboratory, radiographic, and quality of life parameters.
      Symptoms were improved in 8 of 12 patients who had diarrhea, 7 of 12 who had
      flushing, 9 of 12 who had abdominal pain, and in 4 of 7 who had malaise. Elevated
      tumor markers decreased in all patients. Biochemical markers (mean +/- SE) at 3
      months decreased by 60% +/- 6% for 5-HIAA, 75% +/- 10% for chromogranin A and 50%
      +/- 7% for neuron-specific enolase. Tomographic assessment revealed tumor
      liquefaction in 10 of 13 patients. The Karnofsky performance status improved from
      a mean of 66 +/- 2 to 84 +/- 2 (P <0.001). Median follow-up was 16 months, with
      13 deaths occurring from 1 week to 71 months after treatment. CONCLUSIONS:
      Hepatic artery chemoembolization improves symptoms of carcinoid syndrome, has a
      high tumor response rate, and improves short-term quality of life in this group
      of patients with advanced hepatic carcinoid disease.

PMID- 9600290
TI  - Surgical treatment of metastatic melanoma.
AB  - BACKGROUND: The survival of patients with metastatic melanoma is poor. The
      response rates for chemotherapy and immunotherapy have been low, with no real
      improvement in survival. We reviewed the results of surgical resection. METHODS:
      We performed a retrospective review of the medical records of all patients who
      underwent resection of metastases from melanoma from 1979 to 1994. RESULTS: There
      were 77 patients (44 men, 33 women, mean age 51 years). Metastases were resected
      from soft tissue (n = 28), abdominal viscera (n = 22), lung (n = 15), and brain
      (n = 12). Forty-four patients had complete resections, and 33 had incomplete
      resections. Sixty-five patients had solitary lesions and 12 had multiple lesions
      resected. The overall 5-year survival rate was 10%. Patients with solitary
      lesions had a 5-year survival rate of 12%, compared with 0% for patients with
      multiple lesions (P = 0.01). Patients with complete resection had a 5-year
      survival rate of 15%, compared with 4% for patients with incomplete resection (P
      < 0.001). Patients with complete resection of solitary lesions had a 5-year
      survival of 18%. There was no difference in survival between synchronous and
      metachronous resection. Gender, primary site, disease-free interval, and
      metastatic site had no impact on survival rates. CONCLUSIONS: We conclude that
      patients with metastatic melanoma should be resected for (1) relief of symptoms
      such as obstruction and bleeding, (2) solitary lesions that can be completely
      resected, (3) serial lesions that can be completely resected, and (4) selected
      cases that can be rendered macroscopically free of disease. Surgical resection is
      superior to any other available therapy for metastatic melanoma.

PMID- 9600291
TI  - Surgical management of adenocarcinoma of the cardia.
AB  - BACKGROUND: The incidence of adenocarcinoma of the cardia is increasing. The
      surgical management remains controversial. The present study reviews our
      experience with surgically resected adenocarcinoma of the cardia. METHODS: A
      retrospective review of 153 cases of surgically resected adenocarcinoma of the
      cardia was performed. Preoperative radiotherapy was used in 31 patients. The
      surgical approach, morbidity, mortality, impact of preoperative radiotherapy, and
      survival were determined. RESULTS: The type of resection performed was a
      transhiatal esophagogastrectomy in 78%, a transthoracic esophagogastrectomy in
      21%, and a transabdominal esophagogastrectomy in 1%. The in-hospital mortality
      rate was 4%. The frequency of complications was not associated with the use of
      preoperative radiotherapy or surgical approach. The 1-year (61%), 2-year (38%), 3
      year (23%), and 5-year (16%) survival were not affected by the use of
      preoperative radiotherapy or surgical approach. Survival was significantly
      associated with stage and the presence of lymph node metastasis. CONCLUSIONS:
      Adenocarcinoma of the cardia is associated with a poor long-term prognosis. The
      long-term survival does not appear to be affected by the use of preoperative
      radiotherapy or by surgical approach.

PMID- 9600292
TI  - Relationships between operative approaches and outcomes in esophageal cancer.
AB  - BACKGROUND: Controversy exists whether patients with esophageal carcinoma are
      best managed with Ivor-Lewis (IL) or transhiatal (TH) esophagectomy. The TH
      approach is presumed to be superior with respect to operative time, leak rates,
      morbidity/mortality, and length of stay (LOS), but may represent an inferior
      cancer operation compared with formal IL. Accordingly, we reviewed the results of
      our esophageal resections to compare these outcome parameters for each operative
      approach. METHODS: We performed a retrospective review of all esophagectomies
      performed at Oregon Health Sciences University and Portland Veterans Affairs
      Medical Center between 1987 and 1996. Survival was determined by the Kaplan-Meier
      method, and comparisons between the IL and TH groups were made with Student's t
      test, Fisher's exact test, and log-rank analysis. RESULTS: Seventy-eight patients
      were identified. Forty patients had IL and 38 had TH. Fifty-eight patients had
      adenocarcinoma, 19 had squamous cell, and 1 had an unknown histology. Mean
      operative time was 389 minutes for IL versus 275 minutes for TH (P = 0.0001).
      Leak rates were 7.5% for IL and 13% for TH (P = 0.21). There were no significant
      differences between IL and TH with respect to other types of complications,
      operative deaths, blood loss, need for transfusion, LOS, stricture rates, or need
      for dilatation. Overall mean survival was 12 months. Mean survival rates were 8
      months for IL and 12 for TH (P = NS), and were also equivalent when compared by
      histology and stage for stage. CONCLUSIONS: We conclude that IL and TH are
      comparable operations with equivalent survival rates. The TH approach did not
      decrease the incidence of complications, transfusions, leaks, strictures, or
      subsequent dilatations. Although TH requires less operating room time, this does
      not translate into a decrease in LOS. Either approach appears to be acceptable
      depending on surgeons' preferences and appropriate patient selection.

PMID- 9600293
TI  - Intraductal neoplasms of the pancreas.
AB  - BACKGROUND: Since 1980 a group of pancreatic tumors have been termed intraductal
      papillary mucinous tumors (IPMT). Because these tumors occupy an intraductal
      position they are demonstrated by pancreatography to reside in the main
      pancreatic duct (MPD) or side branch ducts (SBD). Lesions of IPMT result in
      abdominal pain or pancreatitis symptoms because mucin production or papillary
      growth results in ductal obstruction. Only 104 cases had been reported in the
      literature by 1996 but more are being presented in abstract form. We reviewed our
      own 33 cases to assist defining operative decision-making criteria. METHODS: All
      cases of IPMT between 1989 and 1997 were reviewed for clinical presentation,
      anatomy by endoscopic retrograde cholangiopancreatography and computed
      tomography, histologic findings, and long-term outcomes. RESULTS: Our cases were
      older (65 years) and presented with disease centered mainly in the head of the
      gland. Clinical presentation was epigastric pain (82%), pancreatitis (56%),
      weight loss (36%), diabetes (27%), and jaundice (9%). Operations were
      pancreatectomy in 31 (Whipple n = 15, total n = 5, distal n = 10, local n = 1),
      bypass only (n = 1), and no operation (n = 1). Malignancy was found in 14 of 33
      (42%). Factors significantly associated (P <0.05 Fisher exact test) with
      malignancy were history of alcohol abuse or death from disease. Jaundice or
      presence in both MPD and SBD approached a significant association with malignancy
      but not abdominal pain, weight loss, diabetes, preoperative serum elevations of
      amylase, SGOT, CA-19-9, or CEA; diffuse MPD dilation, gland region, gross mucus
      in ducts or filling defects, cytology, calcifications, or a pancreatic mass. In
      31 resected patients after a follow-up of 37 months (1 to 103) death had occurred
      in 6 of 13 malignant cases and 0 of 18 with benign disease. Three-year actuarial
      survival was 82% (all) and 56% (malignant). Symptom recurrence after resection
      was found in 6 of 31 at a mean of 13 months postoperatively and was associated
      with death from disease (P <0.05) or presence of pain preoperatively. CONCLUSION:
      Malignancy is common with IPMT and is more likely to be present with the clinical
      history of alcohol abuse or jaundice and if the tumor involves both the MPD and
      the SBD. The prognosis after resection is better than pancreatic cancer but the
      19% recurrence of symptoms was equally seen with benign or malignant cases owing
      to residual disease in pancreatic remnants. The amount of resection should be
      extensive in patients likely to have malignancy (alcohol, jaundice, MPD+SBD). In
      those likely to redevelop symptoms, ie, those with preoperative pain, a careful
      assessment should be made via imaging studies for extent of disease.

PMID- 9600294
TI  - Management of the neck in parotid cancer.

PMID- 9600295
TI  - Horizons in general surgery.

PMID- 9600296
TI  - History of the Health Physics Society.

PMID- 9600297
TI  - History of the International Radiation Protection Association.

PMID- 9600298
TI  - Soil ingestion by humans: a review of history, data, and etiology with
      application to risk assessment of radioactively contaminated soil.
AB  - Ingestion of soil by humans has been a documented phenomenon for centuries and
      still takes place today according to various literature. The literature reviewed
      here shows that there are two distinct soil ingestion phenomenon: inadvertent and
      purposeful (geophagia). Certain lifestyles, occupations, and living conditions
      will likely put different individuals or different groups at risk to these
      separate, but sometimes related, phenomenon. In particular, reports of geophagia
      are relatively common for the life stages of adolescence and periods of growth,
      and during pregnancy and lactation. Geophagia also appears to be relatively
      common among indigenous peoples on all continents, sometimes taking place to
      extreme degrees. Because of their high dependence on the land, indigenous peoples
      are also at highest risk for inadvertent ingestion. Inadvertent intake is more a
      function of either primitive living conditions or professions that may bring
      workers into close and continual contact with the soil. It is the purpose of this
      report to review and summarize literature related to ingestion of soil by humans
      with emphasis on the relevance of soil ingestion to radiological dose assessment,
      the etiology of geophagia and its relationship to risk assessment, qualitative
      observations and quantitative studies of direct soil ingestion by humans with
      interpretations useful for different lifestyle scenarios, the status of a number
      of current radiological assessment models in accounting for soil ingestion, and
      some unresolved issues in modeling the ingestion of soil.

PMID- 9600299
TI  - Multifractal analysis of the 137Cs fallout pattern in Austria resulting from the
      Chernobyl accident.
AB  - The cumulative deposition of the 137Cs fallout in Austria resulting from the
      passage of the Chernobyl cloud has been investigated by applying correlation
      dimension and hyperbolic frequency distribution methods. For the analysis, a
      total of 1,881 deposition values were used, which were collected by the Federal
      Environmental Agency of Austria and the Federal Ministry of Health, representing
      all available measurements of 137Cs in soil made in Austria after the Chernobyl
      accident. From these data a hyperbolic exponent for the frequency distribution of
      4.0 and a set of fractal correlation dimensions, which decrease from 1.426 +/-
      0.022 (for the whole network) to 0.706 +/- 0.047 (for 137Cs values > or = 100 kBq
      m(-2)), were derived, thus confirming that the fallout pattern can be described
      as a multifractal.

PMID- 9600300
TI  - Geographical distribution of radiation risks in The Netherlands.
AB  - Risk assessment of exposure to sources of radiation is an important tool for
      national governments in regulating radionuclide emissions and thus reducing
      radiation doses for the general public. For this reason radiation doses from
      sources throughout The Netherlands have been analyzed. For sources with well
      defined locations and doses that were thought to vary significantly throughout
      The Netherlands, radiation dose maps were produced. Average dose values were
      calculated or derived from the literature for doses considered to be evenly
      distributed throughout the country or for which no information on the
      geographical distribution of dose was available. Emission, dispersion, and
      individual dose were modeled for each source using various pathways and exposure
      routes. Indoor radon and gamma radiation from building materials generate the
      highest dose values. The highest human induced radiation doses for industries of
      which the doses showed to be geographically distributed are found in the cement
      industry, elemental phosphorus production, phosphoric acid production, and iron
      and steel production. Radiation dose from some of these sources has a very local
      peak and decreases rapidly with distance. The elemental phosphorus production
      causes relatively high radiation doses throughout a large part of The
      Netherlands. Cumulation of doses from various sources occurs, but these are often
      masked by doses from a few large industries.

PMID- 9600301
TI  - Environmental contamination and assessment of doses from radiation releases in
      the Southern Urals.
AB  - The Southern Urals in Russia was contaminated by radioactive discharges into the
      Techa River (1949-1956), the Kyshtym accident (1957), and the current releases
      and discharges from the Mayak Nuclear Materials Production Complex. In this
      paper, the consequences of radioactive contamination of the Ural region are
      analyzed. The current content of 90Sr in the components of food chains is as
      follows (Bq kg(-1) wet weight): potatoes, 0.2-6.7; grain, 0.5-12.6; milk, 0.2
      6.3; beef, 0.2-1.7; lake water, 0.12-1.0; river water, 0.2-8.5; fish, 7-480;
      mushrooms, 400-1,100; and berries, 700-16,000. The content of 137Cs is as
      follows: potatoes, 0.5-3.8; grain, 0.3-2.9; milk, 0.2-4.5; beef, 0.3-2.6; lake
      and river water, 0.002-0.019; fish, 2-32; mushrooms, 110-1,600; and berries, 150.
      A major fraction of the dose to humans comes from the consumption of local food
      products, including natural ones, which have higher contamination levels than
      agricultural products. The average annual dose rates in contaminated areas are
      (0.5-4) x 10(-4) Sv y(-1), which is lower by a factor of 10(2)-10(4) than in the
      periods of "acute" exposure (1950-1951 and 1957-1958). Natural organisms received
      very high doses up to 200-800 Gy resulting from radioactive discharges into the
      Techa River and the radiation accident in 1957. In all cases, including the
      "acute" exposure followed by the chronic irradiation, the doses to biota were by
      a factor of 10-10(3) higher than those to humans.

PMID- 9600302
TI  - Calculation of the effective dose and its variation from environmental gamma ray
      sources.
AB  - Effective dose, an indicator of the stochastic effect of radiation, has been
      widely used in dose evaluation in the environment. Though conversion factors have
      been used to obtain E from the air kerma or air absorbed dose, the variation of
      the conversion factors due to the change of exposure conditions has not been
      sufficiently investigated. This report documents an investigation of the
      variation of the effective dose per air kerma for environmental gamma rays
      depending on the exposure conditions using anthropomorphic phantoms and Monte
      Carlo calculations, taking into account the precise angular and energy
      distributions of the environmental gamma rays incident on the human body. As
      causes of the variation, posture of human bodies, biases of environmental source
      distributions, and body size were considered. The variation of effective dose in
      a prone position compared with that in a standing position was found to be within
      30%. The bias of environmental sources causes the effective dose per air kerma to
      vary by 20% at maximum, but in some cases for low-energy gamma rays the variation
      was found to be up to 40% due to the change in the energy spectrum. The effective
      dose for a new born infant was estimated to be higher than that for an adult by a
      maximum of 80-90% for low-energy gamma rays from anthropogenic sources because of
      a lower shielding effect of the smaller body. The variation of the effective dose
      equivalent shows a similar tendency to the effective dose. Consequently, this
      study made it possible to estimate the uncertainties of effective dose and
      effective dose equivalent evaluated from air kerma or absorbed dose in air using
      the standard available conversion factors.

PMID- 9600303
TI  - Dose reconstruction for residents living in 60Co-contaminated rebar buildings.
AB  - The first 60Co-contaminated rebar building was discovered in Taipei city in 1992.
      As of 18 July 1997, 144 buildings with 1,327 housing units were confirmed to
      contain 60Co-contaminated rebars. All these reinforced concrete buildings were
      constructed between 1982 and 1984. Thousands of residents have been exposed to
      ionizing radiation of various degrees. Preliminary assessments by the Atomic
      Energy Council showed that the accumulated maximal doses ranged from a few mSv to
      several Sv. The purpose of this work was to reconstruct more reliable individual
      doses for epidemiologic and medical uses. This reconstruction provided the best
      estimated doses as well as conceivable upper and lower bounds. The variation of
      residential day-life activities by individual members in a family was considered
      according to their sex, age, profession, etc. Intensive data on exposure rates
      were collected using thermoluminescent dosimeters positioned at 1 m height and 1
      m x 1 m intersections with additional measurements at special locations such as
      bed, sofa, dining table, etc. Thermoluminescent dosimeter measurements were
      performed in all 24 residences studied in this work. This showed that the Atomic
      Energy Council maximal doses were 2-6 times higher than the present best
      estimated doses. Among all family members, elders and housewives received the
      highest doses; children received the lowest doses. The difference in doses among
      all family members belonging to different cohort categories is within a factor of
      two.

PMID- 9600304
TI  - Indoor radon prediction from soil gas measurements.
AB  - This study of radon levels in southwest England investigates the correlation
      between indoor and soil gas radon concentrations and considers the influence of
      geology, meteorological variables, spatial and depth variations. This paper
      examines the value of soil gas measurements as an indicator of potential indoor
      radon concentrations and highlights a number of factors that need to be
      considered. Only a very weak correlation was obtained between the overall 222Rn
      concentration in soil gas and inside the home. However, for high soil gas
      concentrations a stronger correlation with the indoor level was observed.
      Typically, the soil gas concentration was between a factor of 10 and 1,000 times
      greater than that indoors. Levels as low as 10 kBq m(-3) in the soil could
      produce an indoor concentration above the UK action level of 200 Bq m(-3). The
      moisture content and the inhomogeneity of soil permeability were identified as
      chiefly responsible for any perturbation of a soil gas concentration associated
      with a particular geology. Alone, measured soil gas concentrations have only a
      limited use in the prediction of indoor 222Rn concentrations.

PMID- 9600305
TI  - LET dependence of dicentric yields in human lymphocytes induced by low doses of
      sparsely ionizing radiations and its implication for risk assessments.

PMID- 9600306
TI  - Comment on a review of probability of causation and its use in a compensation
      scheme for nuclear industry workers in the UK.

PMID- 9600307
TI  - Comments and corrections on the contaminated rebar incident in Taiwan.

PMID- 9600308
TI  - Issues in the dose-response analysis of the Mayak case-control study.

PMID- 9600309
TI  - Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1
      following genetic immunization with a chimeric DNA vaccine encoding the V3
      inserted into the hepatitis B surface antigen.
AB  - The gp120-derived V3 loop of HIV-1 is involved in co-receptor interaction, it
      guides cell tropism, and contains an epitope for antibody neutralization. Thus,
      HIV-1 V3 is an attractive vaccine candidate. The V3 of the MN strain (MN V3)
      contains both B- and T-cell epitopes, including a known mouse H-2d-restricted
      cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity
      of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the
      highly immunogenic middle (pre-S2 + S) surface antigen of hepatitis B virus
      (HBsAg) was constructed. Epidermal inoculation by gene gun was used for genetic
      immunization in a mouse model. Antibody and CTL responses to MN V3 and HBsAg were
      measured and compared with the immune responses obtained after vaccination with
      plasmids encoding the complete HIV-1 MN gp160 and HBsAg (pre-S2 + S),
      respectively. DNA vaccination with the HIV MN gp160 envelope plasmid induced a
      slow and low titred anti-MN V3 antibody response at 12 weeks post-inoculation
      (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In
      contrast, DNA vaccination with the HBsAg-encoding plasmid induced a rapid and
      high titred anti-HBsAg antibody response and a uniform strong anti-HBs CTL
      response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN
      V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks
      which peaked at 6-12 weeks and remained stable for at least 25 weeks. In
      addition, specific CTL responses were induced in all mice against both MN V3 and
      HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg
      acts as a 'genetic vaccine adjuvant' augmenting and accelerating the cellular and
      humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HBsAg
      plasmid constructs may be useful in DNA immunizations as a 'carrier' of protein
      regions or minimal epitopes which are less exposed or poorly immunogenic.

PMID- 9600310
TI  - Expression and function of c-Met, a receptor for hepatocyte growth factor, during
      T-cell development.
AB  - The c-Met oncoprotein is a cell-surface receptor for hepatocyte growth factor
      (HGF). Signals through HGF and c-Met have been appreciated for their crucial
      roles in the development of many cell types, including liver cells. The present
      study examined whether c-Met is expressed in the thymus and whether c-Met/HGF
      signals can regulate T-cell development in the thymus. We have found that mRNA
      transcripts encoding c-Met are expressed in mouse thymus. The c-Met transcripts
      were expressed at higher levels in fetal and neonatal thymus than in adult
      thymus, and were mostly expressed by lymphoid cells rather than by stromal cells.
      Interestingly, the addition of HGF to fetal thymus organ cultures increased the
      generation of mature T cells expressing high levels of T-cell antigen receptors.
      These results indicate that c-Met is expressed in the thymus during early
      ontogeny, and that c-Met/HGF signals can promote T-cell development.

PMID- 9600311
TI  - Contribution of plasma-derived molecules to mucosal immune defence, disease and
      repair in the airways.
AB  - This review discusses recent observations, in health and disease, on the release
      and distribution of plasma-derived molecules in the airway mucosa. Briefly, the
      new data on airway mucosal exudation mechanisms suggest that the protein systems
      of plasma contribute significantly to the mucosal biology, not only in injured
      airways but also in such mildly inflamed airways that lack oedema and exhibit no
      sign of epithelial derangement. Plasma as a source of pluripotent growth factor,
      adhesive, leucocyte-activating, etc., molecules may deserve a prominent position
      in schemes that claim to illustrate immunological and inflammatory mechanisms of
      the airway mucosa in vivo.

PMID- 9600312
TI  - Cytokine response to group B streptococcus infection in mice.
AB  - This study was undertaken to better understand the complex relationship between
      specific and non-specific host defence mechanisms and group B streptococci (GBS).
      A comprehensive kinetics analysis of cytokine mRNA expression was performed, by
      Northern blot assay, in peritoneal exudate cells (PEC) and spleen cells (SC)
      recovered from CD-1 mice at various times during the course of an intraperitoneal
      infection with a lethal dose (5 x 10(3) microorganisms/mouse) of type Ia GBS,
      reference strain 090 (GBS-Ia). Analysis of cytokines involved in the development
      of a specific TH response shows that GBS-Ia in PEC induce only a weak increase of
      IL-2 mRNA expression and in SC a cytokine pattern characterized by IL-2, IFN
      gamma and IL-12 in the absence of IL-4, IL-5 and IL-10. This selected cytokine
      pattern could provide appropriate conditions for the development of a TH1
      response. Analysis of inflammatory cytokines, which are usually induced early
      during an in vivo infection, shows that there is a significant expression of mRNA
      specific for IL-1beta, TNFalpha and IL-6, both in PEC and SC only at 24 h which
      persists at a high level until 36 h. This delayed cytokine induction, accompanied
      by the contemporary activation of splenic phagocytic cells, occurs only when the
      number of GBS-Ia is extremely high. In fact, at 24 h GBS-Ia have heavily
      colonized all organs. In vitro infection of thioglycollate-elicited peritoneal
      macrophages confirms that the ability of GBS-Ia to induce a strong inflammatory
      cytokine response depends strictly on the number of infecting microorganisms.
      Indeed, macrophages respond to GBS-Ia with a very rapid induction of IL-1beta and
      TNFalpha mRNA when infected at a ratio of 1:10, but not at 100:1. Two major
      observations emerged from this study: (1) GBS-Ia, by inducing a cytokine pattern
      which seems to favour development of a TH1 response, could evade antibody
      production essential for resistance to GBS; and (2) inflammatory cytokine
      response is induced when a heavy microbial invasion of the host has already
      occurred. These novel features of GBS-Ia could contribute to the development and
      progression of lethal infection in mice.

PMID- 9600313
TI  - Induction of human leukaemic mast cell differentiation by fibroblast
      supernatants, but not by stem cell factor.
AB  - In order to explore the potential existence of human mast cell growth factors
      other than stem cell factor (SCF), we have compared SCF to L-cell fibroblast
      supernatants (LCS) during in vitro mast cell differentiation, using human
      leukaemic mast cells (HMC-1 cells) which contain a gain-of-function mutated SCF
      receptor (c-Kit) as model. At baseline, cells exhibited an immature phenotype,
      with <25% being metachromatic or chloroacetate esterase, tryptase and
      FcepsilonRIalpha positive. Intracellular levels of histamine, tryptase, TNF-alpha
      and chymase were low, whereas 83% of cells were c-Kit positive. During a 10 day
      culture with 30% LCS, a significant, time-dependent increase of all mast cell
      markers, except for chymase and c-Kit, was observed at the protein and for
      tryptase and FcepsilonRIalpha also at the mRNA level. Cytoplasmatic granulation
      and stimulated histamine and leukotriene C4 release were increased as well. In
      contrast to LCS, rhSCF induced none of these changes in HMC-1 cells. On Sephadex
      G100 fractionation of LCS, HMC-1 cells increased tryptase activity with fractions
      between 40 and 60, and below 10 kDa, away from the SCF peak. These data show that
      HMC-1 cells fail to differentiate in response to SCF and that in addition to SCF,
      LCS contains other human mast cell growth factors.

PMID- 9600314
TI  - Phenotype of rat monocytes during acute kidney allograft rejection: increased
      expression of NKR-P1 and reduction of CD43.
AB  - Monocytes and macrophages mediate cytotoxicity after appropriate activation and
      thus represent effectors secondary to T lymphocytes and natural killer (NK)
      cells. However, very little is known about the role of activated monocytes in
      organ allograft rejection. In this study, isogeneic (LEW to LEW) and fully
      allogeneic (DA to LEW) rat kidneys were grafted to bilaterally nephrectomized
      recipients. Four days after transplantation a comprehensive sample of leucocytes
      was recovered by perfusion of the recipients' vasculature with phosphate-buffered
      saline containing EDTA (PBS/EDTA). Monocytes were enriched by density gradient
      centrifugation and their physical parameters and immunophenotype were
      investigated by flow cytometry in comparison with untreated, specified pathogen
      free (SPF) LEW rats. Isotransplantation and allotransplantation of kidneys
      dramatically increased the absolute number of intravascular monocytes in the
      recipient. Analysis of NKR-P1 (CD161), CD4, CD62L, CD43, CD11a, CD18 and MHC
      class II expression identified at least two monocyte populations in all
      experimental groups. In graft recipients it was evident that activated monocytes
      were able to express and upregulate NKR-P1 and CD8, which have not been detected
      in these cells to date. If activated monocytes utilize NKR-P1 and CD8, by analogy
      to NK cells and lymphocytes these cells may be endowed with additional pathways
      to upregulate cytolytic functions and effect allograft damage.

PMID- 9600315
TI  - Induction of apoptosis reduces immunogenicity of human T-cell lines in mice.
AB  - Apoptotic cells, e.g. postinflammatory neutrophils, were reported to be engulfed
      by phagocytes without induction of an inflammatory response. We investigated the
      humoral immune response of BALB/c mice after repeated injection of viable or
      apoptotic human T cells. Following interleukin-2 (IL-2) deprivation,
      phytohaemagglutinin (PHA)/IL-2 expanded human T-cell lines were irradiated with
      UV-B light to induce apoptosis, confirmed by propidium iodide staining of Triton
      X-100-lysed cells. Indirect immunofluorescence was used to detect antilymphocyte
      antibodies 7 days after each injection. We found high levels of antilymphocyte
      antibodies in all animals immunized with viable T cells, whereas animals injected
      with apoptotic cells showed a significantly reduced humoral immune response. We
      conclude that apoptotic cells induce poor xenoreactive T-cell responses when
      compared with viable cells.

PMID- 9600316
TI  - A glycosylated Bence Jones protein and its autologous amyloid light chain
      containing potentially amyloidogenic residues.
AB  - Amyloidosis is characterized by deposition of protein fibrils in various tissues.
      The wide variety of sequences of both amyloidogenic and non-amyloidogenic
      immunoglobulin light chains makes them a unique tool for addressing the
      importance of primary structure in the formation of insoluble fibrils. In this
      study, we have determined the primary structure of the kappa I immunoglobulin
      light chain from both the urinary Bence Jones protein and the deposited amyloid
      fibrils of a patient (MH) with primary amyloidosis. The sequence identity of
      urinary-excreted and tissue-deposited light chains excluded biclonality and
      somatic mutations and confirmed that the light chain existed in both a soluble
      and an insoluble form. Several residues have been previously reported to be
      significantly associated with amyloidogenic kappa chains. Many of these were
      found in the MH sequence, including Asp31, Asn45, Phe49, Gln55, His70, Asn/Gly93
      and ProN/Val96, thereby supporting their potential role in fibrillogenesis. In
      addition, Asn20 and Pro60 of protein MH replaced the normally conserved Thr20 and
      Ser60. Asn20 was glycosylated in both the Bence Jones and the amyloid fibril
      protein MH. Cumulative effects of amyloid-associated residues and glycosylation
      might have rendered the immunoglobulin light chain MH prone to fibril formation.

PMID- 9600317
TI  - Blockade of B7-2, not B7-1, inhibits purified protein derivative-primed T
      lymphocyte responses but fails to influence the proportion of Th1 versus Th2
      subsets.
AB  - The ability to select for a cell-mediated response rather than antibody
      production following infection with intracellular mycobacteria, would be an
      advantage in preventing the occurrence of disease. Recent work suggests that the
      two members of the B7 family of costimulatory molecules, B7-1 and B7-2, may
      differentially influence the nature of primary immune responses but little is
      known of their role in this capacity in secondary responses. We have used an in
      vitro model to investigate whether blocking B7-1 and B7-2 affects changes in the
      cytokine profiles of Th lymphocytes previously primed to purified protein
      derivative (PPD) from Mycobacterium bovis. In C57BL/6 and BALB/c mice we found
      that the proliferative responses of a component of recently activated T
      lymphocytes, and those returning to the resting state, were inhibited by B7-2
      blockade. B7-1 blockade had no distinguishable effect. However, in cultures
      containing anti-B7-2 antibody, the production of both interferon-gamma (IFN
      gamma) and interleukin-4 (IL-4), indicative of cell-mediated and antibody
      responses, respectively, were reduced. This suggests that intervention in a
      recall response to mycobacterial antigen by blocking B7-1 or B7-2 molecules, is
      unlikely to alter the nature of the immune response.

PMID- 9600318
TI  - Immunological effects of a hyperinsulinaemic euglycaemic insulin clamp in healthy
      males.
AB  - The purpose of this study was to determine the in-vivo and in-vitro effects of
      insulin, at physiological and supraphysiological concentrations, on the human
      immune system. Ten healthy young men went through a sequential two-step
      hyperinsulinaemic euglycaemic clamp. Plasma insulin concentrations were increased
      from baseline (9.0 microU/ml) to 49.1 microU/ml after 1 h of insulin infusion
      (step I) and to 1281 microU/ml (step II) after 2 h of infusion. As control
      experiments infusions of isotonic saline were performed. The unstimulated natural
      killer (NK) cell activity among blood mononuclear cells (BMNC) increased in
      response to supraphysiological plasma insulin levels (baseline versus step II:
      20.6 +/- 11.3 versus 27.8 +/- 14.4%). The percentages of the D16+ NK cells did
      not change, indicating an enhanced cytotoxic capability per individual NK cell.
      Insulin also slightly increased the activity of NK cells in vitro. A decline at
      step II in the concentrations of monocytes (0.29 +/- 0.09 versus 0.12 +/- 0.03 x
      10(9)/L), lymphocytes (1.57 +/- 0.46 versus 1.22 +/- 0.25 x 10(9)/L), and
      CD16+(24.2 +/- 17.5 versus 16.7 +/- 11.2 x 10(7)/L), CD14+ (20.9 +/- 10.8 versus
      8.6 +/- 3.9 x 10(7)/L), HLA-DR+ (37.2 +/- 22.1 versus 19.2 +/- 10.7 x 10(7)/L)
      and CD45RO+ (91.6 +/- 33.4 versus 61.7 +/- 6.4 x 10(7)/L) cells as well as in the
      percentages of CD14+ cells (11.2 +/- 4.7 versus 6.4 +/- 2.3%) and CD14+/HLA-DR+
      monocytes (9.7 +/- 3.9 versus 4.8 +/- 2.8%) were observed. No changes were found
      at step I. Hyperinsulinaemia did not change the percentages of the CD3+, CD4+,
      CD8+, CD19+, CD56+, CD11a+, CD45RO+ and CD45RA+ cells, the numbers of circulating
      immunoglobulin (Ig)G-, IgA- and IgM- secreting cells, or the proliferative
      responses of BMNC to phytohaemagglutinin, purified derivative of tuberculin or
      interleukin (IL)-2. Hyperinsulinaemia did not change the in-vitro sensibility to
      insulin. In conclusion, supraphysiological insulin levels increased the activity
      of the individual NK cells, but decreased the numbers of NK cells, lymphocytes
      and activated monocytes. The findings are presumably of minor clinical relevance
      but may indicate an insulin-induced immune activation.

PMID- 9600319
TI  - Endogenous interleukin-4 does not suppress the resistance against a primary or a
      secondary Listeria monocytogenes infection in mice.
AB  - Interleukin-4 (IL-4), a cytokine produced by T-helper 2 (Th2) cells, can inhibit
      the development of T-helper 1 (Th1) cells, which results in a decreased release
      of cytokines by the latter. As interferon-gamma (IFN-gamma), produced by Th1
      cells, is involved in the resistance against a Listeria monocytogenes infection,
      the role of endogenously formed IL-4 during a Listeria infection in mice was
      investigated. Neutralization of endogenously formed cytokines by subcutaneously
      injected alginate-encapsulated monoclonal antibody (MoAb)-forming cells results
      in high antibody titres in the circulation over a long time period. The aim of
      the present study was to reevaluate the effect of neutralization of IL-4 during a
      primary Listeria infection and to investigate the role of IL-4 during a secondary
      infection in mice using encapsulated MoAb-forming cells. During the course of a
      primary infection in mice given anti-IL-4 antibody-forming cells (anti-IL-4-FC),
      the number of Listeria found in the liver and spleen was comparable to that found
      in control mice given anti-beta-galactosidase antibody-forming cells (anti-beta
      gal-FC). Activation of macrophages measured by inhibition of Toxoplasma gondii
      proliferation and the release of reactive nitrogen intermediates (RNI) was not
      affected by anti-IL-4-FC treatment during infection. Furthermore, during a
      secondary L. monocytogenes infection the number of bacteria in the liver and
      spleen of anti-IL-4-treated immune mice was comparable to anti-beta-gal-FC
      treated, control, immune mice. The concentration of IFN-gamma in plasma of anti
      IL-4-treated immune mice was similar to that of control immune mice. Taken
      together, these findings demonstrate that neutralization of endogenously formed
      IL-4 does not affect resistance to a primary or a secondary L. monocytogenes
      infection in mice.

PMID- 9600320
TI  - Mice deficient for the complement factor B develop and reproduce normally.
AB  - Factor B is an essential component of the complement cascade which forms the C3
      and C5 convertase of the alternative pathway. Factor B cleavage products also
      function as cofactors in antibody-independent monocyte-mediated cytotoxicity,
      macrophage spreading, plasminogen activation and proliferation of B lymphocytes.
      Several healthy kindreds heterozygous for the factor B null or non-functional
      allele have been reported but the absence of homozygous factor B deficiency in
      humans or in animals has been speculated to be caused by the lethality of the
      phenotype. Here we report the generation of factor B-deficient mice by gene
      targeting in vivo. These mice were born at the expected Mendelian ratio and they
      both develop and breed normally in a conventional animal facility. These mice
      represent a model of complete alternative pathway deficiency. This model enables
      the dissection of the complement cascade in vivo and the elucidation of the
      relative contribution of this complement pathway in the various physiological and
      pathological phenomena ascribed to the complement system.

PMID- 9600321
TI  - Allospecific helper T-lymphocyte repertoire in monozygotic twins.
AB  - In the course of maturation in the thymus there is a selection of T lymphocytes
      based on the avidity between their T-cell receptors and HLA/peptide complexes
      expressed on stromal thymic cells. The repertoire of mature T lymphocytes is
      further modulated by encounters with foreign antigens. Thus, the antigen specific
      repertoire of the peripheral T-lymphocyte pool is determined by genetic and
      environmental factors. We recently reported that pairs of monozygotic twins often
      display significant differences in their allospecific cytotoxic T-cell
      repertoire, suggesting an important role of confrontation with foreign antigens
      on the CD8+ T-cell repertoire. We have now performed similar studies on the
      repertoire of allospecific CD4+ T lymphocytes. Using positively selected CD4+ T
      cells in limiting dilution analyses we compared the differences in the
      allospecific helper T-lymphocyte precursor frequencies (HTLpf) between pairs of
      genetically identical monozygotic twins and pairs of unrelated, HLA disparate
      individuals. We found that all monozygotic twin pairs and most unrelated pairs
      had similar HTLpf to the same stimulator, i.e. the 95% confidence intervals were
      overlapping. However, when studied in greater detail, the differences in HTLpf
      within monozygotic twin pairs were found to be significantly smaller than the
      differences within pairs of unrelated responders. Thus, we find evidence of an
      influence by environmental antigens also on the repertoire of allospecific CD4+ T
      cells, but polymorphic genetic factors seem to be more important here than for
      the repertoire of allospecific CD8+ T cells.

PMID- 9600322
TI  - Opsonophagocytic and bactericidal activity mediated by purified IgG subclass
      antibodies after vaccination with the Norwegian group B meningococcal vaccine.
AB  - To study how the different immunoglobulin (Ig)G subclass antibodies may confer
      protection against systemic meningococcal disease, we isolated IgG1, IgG2 and
      IgG3 antibodies from plasma from vaccinees immunized with the Norwegian
      meningococcal outer membrane vesicle vaccine. Four IgG1, one IgG2 and four IgG3
      preparations were purified. The IgG2 and IgG3 subclass preparations were free
      from contaminating subclasses, whereas the IgG1 preparations contained from 0 to
      14% of IgG2 and/or IgG3. Immunoblotting against whole-cell meningococcal antigens
      showed broad specificities of the various preparations, both within and between
      subclasses. These subclass preparations were tested for opsonophagocytic and
      bactericidal activity. As targets we used two different variants of the
      meningococcal vaccine strain, with low (44/76-SL) and high (44/76-1) expression
      of the outer membrane protein Opc. Using polymorphonuclear leucocytes as effector
      cells in the presence of human complement, all three IgG subclass preparations
      revealed high, and similar, opsonophagocytic activities against 44/76-SL, whereas
      against 44/76-1 the IgG2 preparation showed a reduced activity and most IgG3
      preparations were slightly more active than the IgG1 preparations. Regarding
      bactericidal activity, all the three subclasses were highly active against 44/76
      SL. Against 44/76-1 the bactericidal activities were somewhat more varied: all
      IgG1 and three IgG3 preparations exhibited higher activities than against 44/76
      SL. Due to the low concentration in the IgG2 preparations, only a weak activity
      was seen against 44/76-1. One IgG3 preparation that was highly opsonophagocytic
      revealed no bactericidal activity against either of the two bacterial variants
      examined. In conclusion, we have shown that the IgG subclass effector functions
      differ from person to person, but that antibodies of IgG1, IgG2 and IgG3
      subclasses, judged by their behaviour in the functional tests, may all contribute
      to protection against meningococcal disease.

PMID- 9600323
TI  - Linkage between inflammation and coagulation: an update on the molecular basis of
      the crosstalk.
AB  - Inflammation and coagulation cannot be considered as two separate processes,
      since there are several connecting points making them part of unique, defensive
      host response. The endothelium can be considered as the first link between
      inflammation and coagulation, since damaged endothelium during inflammation
      represents a surface where proteins involved in both coagulation and the
      development of inflammation are expressed. During inflammation, cytokines
      modulate the coagulation system by downregulating the expression of
      thrombomodulin and the activation of protein C pattern but, at the same time,
      they induce the expression of tissue factor, modifying, in this way, the balance
      between procoagulant and anticoagulant activities. At the same time, at the site
      of tissue injury, platelets become activated and release several mediators that
      modify tissue integrity. Thrombin, formed following activation of the coagulation
      cascade, is essential to promote haemostasis but also stimulates several cell
      functions, including chemotaxis and mitogenesis, which are responsible for the
      spreading of the lesion and the tissue repair process. Therefore, in the study of
      inflammation the involvement of the coagulation pathway has to be taken into
      account, since the interaction between coagulation and inflammation pathways is a
      critical issue.

PMID- 9600324
TI  - Comparison of D2 and D3 dopamine receptor affinity of dopaminergic compounds in
      rat brain.
AB  - This study used quantitative autoradiography to simultaneously evaluate the
      relative affinities of dopaminergic compounds for dopamine D2 and D3 receptors in
      rat brain. PD 152255, PD 128907, and l-nafadotride exhibited significantly higher
      affinity for cerebellar dopamine D3 sites than [3H]quinpirole-labeled sites in
      caudate/putamen (6.3-, 6.0-, and 2.3-fold, respectively). In contrast,
      chlorpromazine, risperidone, and domperidone were more potent at striatal
      dopamine D2 receptors (3.8-, 31-, and 40-fold, respectively). Dopamine,
      quinelorane, (+)-UH 232, and RS-trans-7-OH-PIPAT exhibited relatively little
      D2/D3 selectivity.

PMID- 9600325
TI  - Effects of uroguanylin and guanylin against antigen-induced bronchoconstriction
      and airway microvascular leakage in sensitized guinea-pigs.
AB  - Uroguanylin and guanylin are isolated mainly from the gastrointestinal tract and
      are activators of guanylyl cyclase C receptor (GC-C), which mediates the
      production of intracellular cyclic guanosine 3',5'-monophosphate (cyclic GMP).
      The bronchodilator effects of agents that raise cyclic GMP levels, such as atrial
      natriuretic peptide, have been reported, and uroguanylin mRNA has recently been
      detected in extra-gastrointestinal tissues, including the lung, suggesting their
      role in pulmonary activity. In the first step of this study, we examined the
      relaxant effects of uroguanylin and guanylin on isolated tracheal smooth muscle
      of guinea-pigs, and measured tissue cyclic GMP levels by means of
      enzymeimmunoassay. Uroguanylin produced concentration-dependent relaxant effects
      on resting tone and significant elevated cyclic GMP levels. Guanylin produced the
      same, but less potent, effects. In this study, we first investigated the effects
      of uroguanylin and guanylin on antigen-induced bronchoconstriction and airway
      microvascular leakage in actively sensitized guinea-pigs. Anesthetized male
      guinea-pigs, ventilated via a tracheal cannula, were placed in a plethysmograph
      to measure pulmonary mechanics for 10 min after challenging with 1 mg/kg of
      ovalbumin. Evans blue dye was then extravasated into their airway tissues to
      measure microvascular leakage. Intravenous pretreatment with uroguanylin
      significantly inhibited ovalbumin-induced bronchoconstriction and microvascular
      leakage in a dose-dependent manner. These inhibitory effects were mimicked by 8
      bromoguanosine 3', 5'-cyclic monophosphate. This study is the first to show that
      uroguanylin not only had a potent bronchodilatory effect but also inhibited
      microvascular leakage. These results encouraged us to continue the above
      experimental and clinical studies in bronchial asthma.

PMID- 9600326
TI  - Interactions between ouabain, atrial natriuretic peptide, angiotensin-II and
      potassium: effects on rat zona glomerulosa aldosterone production.
AB  - The effects of ouabain, atrial natriuretic peptide, angiotensin-II and potassium
      on aldosterone production by collagenase dispersed rat zona glomerulosa cells
      were studied. A-II and 10(-4) M ouabain-induced increases in aldosterone
      production was inhibited by 10(-9) M ANP at all potassium concentrations
      examined. 10(-4) M ouabain inhibited the A-II induced increase in aldosterone
      production at all potassium concentrations. The degree of this inhibition was
      smaller at higher potassium levels. Ouabain enhanced the inhibitory effect of ANP
      on A-II-induced aldosterone synthesis at all potassium concentrations.
      Interactions between A-II, ANP, ouabain and potassium may be of physiological
      significance in the regulation of aldosterone secretion.

PMID- 9600327
TI  - Proteasome is a carrier to translocate doxorubicin from cytoplasm into nucleus.
AB  - When an effective concentration of doxorubicin (DXR) was added into L1210 of a
      mouse leukemia cell line, DXR was rapidly distributed much more in the nuclei
      than in the other organelle within a few minutes. A [14C]DXR-binding fraction was
      obtained from the cytosol prepared from L1210 cells. The fraction was adsorbed to
      hydroxylapatite matrix and eluted from the matrix by 50-150 mM potassium
      phosphate buffer. The fraction showed high DXR-binding and Suc-Leu-Leu-Val-Tyr
      MCA-degrading activity. The binding of [14C]DXR was inhibited by unlabeled DXR.
      Gel chromatography of the fraction with Sephacryl S-300 separated two fractions
      of high molecular weight (Peak I, approx. 750 kDa) and low molecular weight (Peak
      II). Peak I showed proteolytic activity. [14C]DXR-binding Peak I had much higher
      affinity to DNA-cellulose than [14C]DXR-binding Peak II. [14C]DXR-Peak I complex
      also was retained into the nuclei isolated from L1210 cells, temperature
      dependently. These results suggest that a specific carrier to translocate DXR
      from cytoplasm into nucleus exists in L1210 cell and the carrier is proteasome.

PMID- 9600328
TI  - Metabolism of the anticancer drug flavopiridol, a new inhibitor of cyclin
      dependent kinases, in rat liver.
AB  - Flavopiridol (FLAP) is a promising novel chemotherapeutic agent currently
      undergoing clinical phase I trials. To examine hepatic metabolism and biliary
      disposition of FLAP we applied the isolated perfused rat liver system. Besides
      FLAP two metabolites were detected by high performance liquid chromatography in
      bile and perfusate. Twenty-five min after FLAP (30 microM) addition to the
      perfusion medium, biliary secretion of metabolite 1 and 2 reached a maximum of
      1.04 +/- 0.52 and 11.34 +/- 4.72 nmol/g.liver.min, respectively. Biliary
      excretion of parent FLAP, however, continuously increased for 60 min up to 406 +/
      134 pmol/g liver.min. In the perfusate, metabolite 1 was below detection limit
      and release of metabolite 2 was low (2.8 +/- 0.7 pmol/g liver.min after 60 min).
      Enzymatic hydrolysis with beta-glucuronidase, mass spectroscopy and electron
      absorption spectroscopy revealed that both metabolites are monoglucuronides with
      the glucuronide in position 5 and 7 of the flavonoid core, respectively. The
      amount of FLAP, metabolite 1 and metabolite 2 excreted into bile during the 60
      min of perfusion was 1.94 +/- 0.91, 5.15 +/- 1.95 and 57.29 +/- 23.60% of FLAP
      cleared from the perfusate during 60 min, respectively. In contrast to the
      structurally similar flavonoids genistein and daidzein, no inhibition of UDP
      glucuronyltransferase with methylumbelliferone as a substrate was observed
      indicating that different UDP-glucuronyltransferase isoforms are involved in FLAP
      metabolism. In conclusion, we find that glucuronidation is the major mechanism of
      hepatic FLAP biotransformation. Metabolites are mainly excreted into bile but
      also released into systemic circulation. The pharmacological and toxicological
      effects of these metabolites remain to be elucidated.

PMID- 9600329
TI  - Histamine and spontaneous motor activity: biphasic changes, receptors involved
      and participation of the striatal dopamine system.
AB  - The time- and dose-related effects of exogenous histamine on spontaneous motor
      activity and receptors involved were evaluated in male rats.
      Intracerebroventricular administration of histamine (5.4 and 54.3 nmol) produced
      a biphasic effect with initial transitory hypoactivity and later hyperactivity
      expressed by locomotion frequency in an open-field. The rearing frequencies were
      only reduced by all doses of histamine used. The histamine-induced hypoactivity
      was inhibited by the H3-antagonist thioperamide and was also induced by the H3
      agonist N-alpha-methylhistamine. The histamine-induced hyperactivity phase was
      blocked by the H1-antagonist mepyramine. The H2-antagonist ranitidine increased
      locomotion and rearing frequencies. The participation of other neurotransmitters
      in the persistent hypokinetic effect induced by 135.8 nmol of histamine was
      determined by HPLC in the striatum and hypothalamus as counter-proof. A decreased
      DOPAC/DA ratio was observed only in the striatum. In the hypothalamus, low levels
      of 5HT were detected, probably not correlated with motor activity. In conclusion,
      the present results suggest that the exogenous histamine-induced hypoactivity
      response is probably due to activation of H3-receptors as heteroreceptors
      reducing the activity of the striatal dopaminergic system. This effect can
      partially overlap with the expression of the hyperactivity induced by H1-receptor
      activation. The participation of H2-receptors requires further investigation.

PMID- 9600330
TI  - Effect of 12, 24 and 72 hours fasting in thermogenic parameters of rat brown
      adipose tissue mitochondrial subpopulations.
AB  - The aim of the present work was to study the effects of various durations of
      fasting (12, 24 and 72 hours) on brown adipose tissue (BAT) thermogenic
      parameters--cytrochrome-c-oxidase (COX) activity, GDP-binding activity and
      uncoupling protein (UCP1) content--and also on morphological features of
      different mitochondrial subpopulations, obtained by differential centrifugation-
      M1 (1000 g), M3 (3000 g) and M15 (15,000 g) fractions. The mitochondrial
      subpopulations showed morphological differences and a different distribution of
      UCP1 levels and of GDP-binding in all experimental groups. Starvation induced a
      decrease in the average size for all mitochondrial subtypes. The main changes
      induced by fasting in thermogenic parameters were observed in the M15 subtype.
      After the first 24h of starvation, there was a significant decrease of UCP1
      levels only in the lightest mitochondrial subpopulation. However, the 72h fasted
      situation reflected a tendency to increase UCP1 content and UCP1/COX ratio
      together with a significant decrease of GDP-binding/UCP1 ratio, thus indicating
      more masked GDP-binding sites. Important fasting-induced changes in both
      morphological and biochemical parameters in BAT mitochondrial subtypes reflect
      their role in the physiological response of BAT to starvation.

PMID- 9600331
TI  - Thermal properties of adamantanol derivatives and their beta-cyclodextrin
      complexes in phosphatidylcholine bilayers.
AB  - Differential Scanning Calorimetry (DSC) has been applied to study the thermal
      properties of the membrane perturbing antibacterial octyl- and dodecyl-bromide
      salts of quaternary dimethylamino adamantanol (ADM-8 and ADM-12 correspondingly)
      incorporated in free or complexed form with beta-cyclodextrin (beta-CD) into
      dipalmitoylphosphatidylcholine (DPPC) containing bilayers. The DSC results showed
      that the studied compounds exert pronounced thermotropic changes in DPPC bilayers
      when inserted as free molecules. These effects are reduced when are present in a
      complex form with beta-CD. Since the studied compounds exert destructive effects
      in membrane bilayers their insertion in membrane bilayers as complexes with
      cyclodextrin may result in differentiation of their activity. The obtained
      results suggest that their complexation with beta-CD may improve their biological
      profile. It also increases their aqueous solubility, a limited factor for their
      use as drugs.

PMID- 9600332
TI  - Inhibition of tumor necrosis factor-alpha production by SK&F 98625, a CoA
      independent transacylase inhibitor, in cultured rat peritoneal macrophages.
AB  - When rat peritoneal macrophages were incubated in medium containing thapsigargin,
      tumor necrosis factor-alpha (TNF-alpha) production was increased time
      dependently. In the presence of SK&F 98625, a CoA-independent transacylase
      inhibitor, the thapsigargin-induced TNF-alpha production was inhibited dose
      dependently. Platelet-activating factor (PAF) and prostaglandin E2 (PGE2)
      production were also inhibited by SK&F 98625. The SK&F 98625-induced inhibition
      of TNF-alpha production was not prevented by addition of PGE2. PAF antagonists
      such as E6123, L-652,731 and CV-6209 partially inhibited the thapsigargin-induced
      TNF-alpha production, suggesting that concurrently produced PAF in thapsigargin
      stimulated macrophages up-regulates TNF-alpha production. The inhibition by SK&F
      98625 of thapsigargin-induced TNF-alpha production might be partly due to the
      inhibition of PAF production.

PMID- 9600333
TI  - Flufenamic and tolfenamic acids and lemakalim relax guinea-pig isolated trachea
      by different mechanisms.
AB  - The effects of K+ channel inhibitors on the relaxations induced by flufenamic and
      tolfenamic acids and lemakalim were examined in guinea-pig isolated trachea
      precontracted with prostaglandin F2alpha (PGF2alpha, 1 microM). Flufenamic and
      tolfenamic acids (0.1-33 microM) and lemakalim (0.01-33 microM) relaxed guinea
      pig trachea in a concentration-dependent manner. Tetraethylammonium (0.5-2 mM), a
      nonspecific inhibitor of K+ channels, inhibited the relaxations induced by
      flufenamic and tolfenamic acids without affecting lemakalim-induced relaxation.
      Charybdotoxin (ChTX, 33-100 nM), an inhibitor of the large Ca2+-activated K+
      channels (BK(Ca)), also inhibited the relaxations induced by flufenamic and
      tolfenamic acids without affecting lemakalim-induced relaxation. Glipizide (3.3
      33 microM), an inhibitor of the ATP-sensitive K+ channels (K(ATP)) inhibited
      lemakalim-induced relaxation without affecting those induced by flufenamic and
      tolfenamic acids. Our results indicate that the relaxations of guinea-pig
      isolated trachea by flufenamic and tolfenamic acids are due to activation of
      BK(Ca). The relaxant mechanism of flufenamic and tolfenamic acids thus differs
      from that of lemakalim, an activator of K(ATP).

PMID- 9600334
TI  - Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus
      cavernosum smooth muscle cells.
AB  - In human corpus cavernosum, release of nitric oxide from the non-adrenergic, non
      cholinergic nerves and/or the endothelium activates guanylyl cyclase and
      increases intracellular cGMP levels. The increase in intracellular cGMP modulates
      intracellular calcium and in turn regulates smooth muscle contractility and
      erectile function. Phosphodiesterases play an important physiological role by
      regulating the intracellular levels of cyclic nucleotides. In this study, we
      investigated the kinetic parameters of inhibition of phosphodiesterase (PDE) type
      5 (E.C. 3.1.4.35 3',5'-cyclic GMP phosphodiesterase) by a novel, high affinity,
      selective PDE type 5 inhibitor, sildenafil, in soluble extracts of human corpus
      cavernosum smooth muscle cells. Sildenafil inhibited PDE type 5 cGMP-hydrolytic
      activity, in the crude extract (Ki=4-6 nM) and in partially purified preparations
      (Ki=2 nM) in a competitive manner, as determined by Dixon plots. Sildenafil (Ki=2
      4 nM) was a more effective PDE type 5 inhibitor than zaprinast (Ki=250 nM).
      Stimulation of intracellular cGMP synthesis by the nitric oxide donor, sodium
      nitroprusside, resulted in less than a 5% increase in cGMP levels in the absence
      of sildenafil and a 35% increase in cGMP levels in the presence of sildenafil, in
      intact cells at physiological temperatures. These results are in accord with the
      clinical observations that sildenafil, taken orally, promotes penile erection
      through increased intracellular cGMP in response to sexual stimulation,
      potentiating smooth muscle relaxation.

PMID- 9600335
TI  - Dithiocarbamates as potential confounders in butadiene epidemiology.
AB  - Hematopoietic neoplasms associated with occupational exposure to 1,3-butadiene
      (BD) have been the subject of controversy. This has largely been due to the
      inconsistent results of epidemiology studies that have reported alternatively no
      or weak associations between exposure to BD and hematopoietic neoplasms.
      Moreover, the specificity of association of BD exposure with individual leukemia
      types remains unclear. In addition, a distinct difference in the pattern of
      leukemia risk has been observed between workers employed in BD monomer production
      and those involved in styrene-butadiene rubber (SBR) production: with no increase
      in leukemia risk observed for exposure to BD monomer alone. These observations
      are consistent with an increase in leukemia risk associated with the SBR process
      but not BD monomer and suggest the possibility that the increase may be the
      result of exposure to confounding factors previously not considered. In this
      regard, evidence is accumulating to suggest that SBR studies may be confounded by
      the presence of an important class of biologically active chemicals employed in
      the rubber industry, dithiocarbamates. The hematotoxicity and immunotoxicity of
      dithiocarbamates have been implicated in a wide range of clinical, animal and
      molecular studies, and an extremely high concordance exists between the risk of
      developing leukemia in SBR production and opportunity for exposure to this class
      of agents. Based on these findings additional studies on the epidemiology,
      carcinogenesis and molecular biology of dithiocarbamates are clearly warranted.

PMID- 9600336
TI  - Nuclear translocation of beta-catenin in hereditary and carcinogen-induced
      intestinal adenomas.
AB  - The physical interaction between beta-catenin and the adenomatous polyposis coli
      (APC) gene, and the ability of APC to regulate cytoplasmic levels of beta-catenin
      suggest a role for beta-catenin in colorectal carcinogenesis. In this study, we
      found that beta-catenin immunoreactivity was detected exclusively in the cell
      membrane and cytoplasm of morphologically normal intestinal epithelial cells with
      predominant distribution in the differentiated nonproliferative cell population.
      In contrast, beta-catenin was localized predominantly in the nucleus of adenomas
      from Min/+ mice and transgenic mice expressing a mutant truncated form of the APC
      gene (Apc(delta716) mice). Beta-catenin was expressed predominantly at the cell
      membrane and cytoplasm of the nontransformed rat intestinal epithelial (RIE-1)
      cells in culture, whereas predominantly nuclear localization of beta-catenin was
      observed in the human colon cancer cell line SW480. In the azoxymethane (AOM)
      treated rats, overexpression and nuclear localization of beta-catenin was
      observed in all adenomas. Previous studies have indicated the incidence of APC
      mutations amongst AOM-induced tumors to be 15% or less. These results demonstrate
      that nuclear localization of beta-catenin is a common event in colorectal
      tumorigenesis.

PMID- 9600337
TI  - Signalling pathways involved in nicotine regulation of apoptosis of human lung
      cancer cells.
AB  - Although nicotine has been implicated as a potential factor in the pathogenesis
      of human lung cancer, its mechanism of action in the development of this cancer
      remains largely unknown. The present study provides evidence that nicotine (a)
      activates the mitogen-activated protein (MAP) kinase signalling pathway in lung
      cancer cells, specifically extracellular signal-regulated kinase (ERK2),
      resulting in increased expression of the bcl-2 protein and inhibition of
      apoptosis in these cells; and (b) blocks the inhibition of protein kinase C (PKC)
      and ERK2 activity in lung cancer cells by anti-cancer agents, such as therapeutic
      opioid drugs, and thus can adversely affect cancer therapy. Nicotine appears to
      have no effect on the activities of c-jun NH2-terminal protein kinase (JNK) and
      p38 MAP kinases, which have also been shown to be involved in apoptosis. While
      exposure to nicotine can result in the activation of the two major signalling
      pathways (MAP kinase and PKC) that are known to inhibit apoptosis, nicotine
      regulation of MAP (ERK2) kinase activity is not dependent on PKC. These effects
      of nicotine occur at concentrations of 1 microM or less, that are generally found
      in the blood of smokers, and could lead to disruption of the critical balance
      between cell death and proliferation, resulting in the unregulated growth of
      cells. The findings suggest caution in the use of smokeless tobacco products to
      treat smoking addiction, as they could have a potentially deleterious effect in
      patients with undetectable early tumour development.

PMID- 9600338
TI  - Spectrum of point mutations in the coding region of the hypoxanthine-guanine
      phosphoribosyltransferase (hprt) gene in human T-lymphocytes in vivo.
AB  - The hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in 6-thioguanine
      (TG) resistant T-lymphocytes is a useful target for the study of somatic in vivo
      mutagenesis, since it provides information about a broad spectrum of mutation.
      Mutations in the hprt coding region were studied in 124 TG-resistant T-cell
      clones from 38 healthy, non-smoking male donors from a previously studied
      population of bus maintenance workers, fine-mechanics and laboratory personnel.
      Their mean age was 43 years (range 23-64) and their hprt mutant frequency was 9.3
      +/- 5.2 x 10(-6) (mean +/- SD, range 1.4-22.6 x 10(-6)). Sequence analysis of
      hprt cDNA identified 115 unique mutations; 76% were simple base substitutions,
      10% were +/-1 bp frameshifts, and 10% were small deletions within exons (3-52
      bp). In addition, two tandem base substitutions and one complex mutation were
      observed. Simple base substitutions were observed at 55 (20%) of 281 sites known
      to be mutable in the hprt coding sequence. The distribution of these mutations
      was significantly different than would be expected based upon a Poisson
      distribution (P < 0.0001), suggesting the existence of 'hotspots'. All of the 87
      simple base substitutions occurred at known mutable sites, but eight were
      substitutions of a kind that have not previously been reported at these sites.
      The most frequently mutated sites were cDNA positions 197 and 146, with six and
      five independent mutations respectively. Four mutations were observed at position
      131, and three each at positions 143, 208, 508 and 617. Transitions (52%) were
      slightly more frequent than tranversions (48%), and mutations at GC base pairs
      (56%) more common than mutations at AT base pairs (44%). GC > AT was the most
      common type of base pair substitution (37%). The majority of the mutations at GC
      base pairs (78%) occurred at sites with G in the non-transcribed strand. All but
      one of eight mutations at CpG-sites were of the kind expected from deamination of
      methylated cytosine. Deletion of a single base pair (-1 frameshift) was three
      times more frequent than insertion of a single bp (+1 frameshift). Almost half
      (6/13) of the small (3-52 bp) deletions within the coding sequence clustered in
      the 5' end of exon 2. Short repeats and other sequence motifs that have been
      associated with replication error were found in the flanking regions of most of
      the frameshifts and small deletions. However, several differences in the local
      sequence context between +/-1 frameshift and deletion mutations were also
      noticed. The present results identify positions 197, 146 and possibly 131 as
      hotspots for base substitution mutations, and confirm previously reported
      hotspots at positions 197, 508 and 617. In addition, the earlier notion of a
      deletion hotspot in the 5'end of exon 2 was confirmed. The observations of these
      mutational cluster regions in different human populations suggest that they are
      due to endogeneous mechanisms of mutagenesis, or to ubiquitous environmental
      influences. The emerging background spectrum of somatic in vivo mutation in the
      human hprt gene provides a useful basis for comparisons with radiation or
      chemically induced mutational spectra, as well as with gene mutations in human
      tumors.

PMID- 9600339
TI  - Mismatch G-T binding activity and MSH2 expression is quantitatively related to
      sensitivity of cells to methylating agents.
AB  - To elucidate mechanisms involved in alkylating drug resistance, Chinese hamster
      cells resistant to methylating agents have been generated upon transfection with
      human DNA. Here it is shown that these Chinese hamster ovary (CHO) variants
      exhibit the tolerance phenotype: they are alkyltransferase deficient (Mex-),
      cross-resistant to 6-thioguanine, exhibit reduced G-T binding (MutS alpha)
      activity and express the mismatch repair protein MSH2 at a significantly lower
      level than the corresponding control. By comparing wild-type cells with different
      tolerant strains that show gradual differences in resistance to methylating
      agents, it was shown that both the G-T binding activity and the amount of MSH2
      protein inversely correlates with the level of methylating drug resistance.
      Although the tolerant cell variants analysed express MSH2 at a significantly
      lower level than the wild-type, MSH2 mRNA expression was not impaired.
      Furthermore, MSH2 promoter activity was not reduced upon transient transfection
      into tolerant cells. The results indicate that quantitative differences in
      expression of components of mismatch repair do exist in mammalian cells that
      affect cell survival upon methylation. It appears that post-transcriptional
      mechanisms are involved in regulation of MSH2 expression.

PMID- 9600340
TI  - Absence of regular alpha2(I) collagen chains in colon carcinoma biopsy fragments.
AB  - The extracellular matrix (ECM) is known to play an active role in numerous
      biological processes such as differentiation, apoptosis and cancer. Extensive
      alterations of epithelial basement membranes and of interstitial ECM are known to
      occur during the progression of most invasive carcinomas. Collagen, which
      represents the major component of the interstitial ECM, is primarily involved in
      the stromal changes at the site of tumor cell invasion. We have previously
      described the occurrence in breast and colon cancer ECM of an oncofetal form of
      collagen, characterized by an acidic chain distinct from those of type I and III
      collagen. In the present paper, we bring evidence that alpha2(I) collagen chains
      in colon cancer tissues expressing the acidic chains, are either overmodified or
      absent, both as protein and as regular mRNA transcripts. The results obtained
      strongly suggest that: i) the disorganisation of the collagen architecture and
      the phenomenon of fibril dispersion, which accompanies the lysis of basement
      membrane, is not only due to the enzymatic degradation of the collagen fibres,
      but presumably also to changes of the collagen molecules deposited in the stroma;
      ii) the neosynthesis of collagen occurring at tumor-host interface is deeply
      deregulated, and therefore to be considered the result of altered collagen gene
      expression correlated with the tumor progression, rather than as a mere defensive
      reaction of the host cells.

PMID- 9600341
TI  - Isolation and characterization of propagable cell lines (HUNC) from the androgen
      sensitive Dunning R3327H rat prostatic adenocarcinoma.
AB  - The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of
      human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized
      as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen
      and prostatic acid phosphatase (PAP) positive. To date, the tumor has been
      maintained by serial passage in vivo because of the lack of an in vitro cell line
      that retains the characteristics of the in vivo tumor. The objective of the
      present study was to establish a propagable cell line from R3327H adenocarcinoma
      that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue
      harvested from an in vivo R3327H tumor was dissociated with collagenase and
      placed into Richter's improved media (with supplements). A cytokeratin-positive
      epithelial cell line (HUNC-E) and a vimentin-positive stromal cell line (HUNC-S)
      were generated from the primary culture, subcultured continuously for >300 days,
      and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on
      several media supplements, including nicotinamide, insulin, transferrin, selenium
      and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and
      PAP throughout the culture period, as confirmed by immunocytochemistry and
      Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone
      (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent
      growth and PSA production, which demonstrated the androgen-sensitive nature of
      the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and
      introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals
      with an average latency of 7 months. RT-PCR and immunocytochemical
      characterization of the HUNC cell lines revealed that the cells expressed several
      growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF
      betas, indicating the establishment of potential autocrine loops in the
      neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the
      characteristics of the epithelial and stromal components of the in vivo R3327H
      tumor, will allow a more thorough and informative molecular and biological
      analysis of prostatic adenocarcinoma.

PMID- 9600342
TI  - Involvement of the proliferating cell nuclear antigen (PCNA) in DNA repair
      induced by alkylating agents and oxidative damage in human fibroblasts.
AB  - The involvement of the proliferating cell nuclear antigen (PCNA) in the process
      of DNA repair induced by alkylating agents or by oxidative damage was
      investigated in human quiescent fibroblasts by immunofluorescence and flow
      cytometry. Transition from soluble to the DNA-bound form of PCNA, was taken as
      the parameter to determine its involvement in repair DNA synthesis. Treatment
      with the alkylating agents methylmethane sulfonate and N-methyl-N'-nitro-N
      nitrosoguanidine resulted in the rapid and dose-dependent increase in the nuclear
      binding of PCNA. Similar results were obtained with compounds such as hydrogen
      peroxide or tert-butyl hydroperoxide, which are known to induce oxidative DNA
      damage. Tert-butyl hydroperoxide may also generate malondialdehyde through a
      reaction of lipid peroxidation. This mutagenic and carcinogenic product has been
      previously shown to form adducts with DNA. Therefore, the possibility that tert
      butyl hydroperoxide could induce DNA damage through this pathway was investigated
      by incubating cells directly in the presence of malondialdehyde. Such treatment
      resulted in an increase in immunofluorescence associated with nuclear-bound PCNA.
      The ability of oxidative and alkylating agents to induce the nuclear binding of
      PCNA was also assessed in proliferating cells. In these conditions, treatment
      with hydrogen peroxide or methylmethane sulfonate, resulted in an increase in
      nuclear-bound PCNA in the G1 and in the G2 + M compartments, but not in S phase.
      At longer times after treatment, PCNA immunostaining was reduced to basal levels,
      while an increase in nuclear binding of p21(waf1/cip1) protein was found in
      concomitance with cell-cycle arrest. These results indicate that agents inducing
      DNA base alterations in vivo, promote the nuclear binding of PCNA. These lines of
      evidence support the role of a PCNA-dependent reaction in the base excision
      repair system.

PMID- 9600343
TI  - Inhibition of DNA cytosine methyltransferase by chemopreventive selenium
      compounds, determined by an improved assay for DNA cytosine methyltransferase and
      DNA cytosine methylation.
AB  - The organoselenium compounds benzyl selenocyanate (BSC) and 1,4
      phenylenebis(methylene)selenocyanate (p-XSC), as well as sodium selenite, are
      effective chemopreventive agents for various chemically induced tumors in animal
      models at both the initiation and postinitiation stages. The mechanisms involved
      at the postinitiation stage are not clear. Because several lines of evidence
      indicate that inhibition of excess DNA (cytosine-5)-methyltransferase (Mtase) may
      be a sufficient factor for the suppression or reversion of carcinogenesis, we
      examined the effects of sodium selenite, BSC, p-XSC and benzyl thiocyanate (BTC),
      the sulfur analog of BSC, on Mtase activity in nuclear extracts of human colon
      carcinomas, and of p-XSC on the Mtase activity of HCT116 human colon carcinoma
      cells in culture. For this purpose, we developed an improved Mtase assay, in
      which the incorporation of the methyl-[3H] group from S-adenosyl[methyl
      3H]methionine into deoxycytidine of poly(dI-dC)-poly(dI-dC), is specifically
      determined by HPLC with radioflow detection after enzymatic hydrolysis, enhancing
      specificity and reliability. In a variation, using SssI methyltransferase and
      labeled S-adenosylmethionine, the overall methylation status of DNA in various
      tissues can also be compared. Selenite, BSC and p-XSC inhibited Mtase extracted
      from a human colon carcinoma with IC50s of 3.8, 8.1 and 5.2 microM, respectively;
      BTC had no effect. p-XSC also inhibited the Mtase activity and growth of human
      colon carcinoma HCT116 cells, with an IC50 of approximately 20 microM. The
      improved Mtase assay should prove to be a reliable method for screening potential
      Mtase inhibitors, especially using cells in culture. We suggest that inhibition
      of Mtase may be a major mechanism of chemoprevention by selenium compounds at the
      postinitiation stage of carcinogenesis.

PMID- 9600344
TI  - Selective increase of the potential anticarcinogen 4-methylsulphinylbutyl
      glucosinolate in broccoli.
AB  - The putative anticarcinogenic activity of Brassica vegetables has been associated
      with the presence of certain glucosinolates. 4-Methylsulphinylbutyl
      isothiocyanate (sulphoraphane), derived from the corresponding glucosinolate
      found in broccoli, has previously been identified as a potent inducer of the
      anticarcinogenic marker enzyme quinone reductase [NADP(H):quinone-acceptor
      oxidoreductase] in murine hepatoma Hepa 1c1c7 cells. We have therefore produced a
      broccoli hybrid with increased levels of this anticarcinogenic glucosinolate and
      tested the ability of extracts to induce quinone reductase. A 10-fold increase in
      the level of 4-methylsulphinylbutyl glucosinolate was obtained by crossing
      broccoli cultivars with selected wild taxa of the Brassica oleracea (chromosome
      number, n = 9) complex. Tissue from these hybrids exhibited a >100-fold increase
      in the ability to induce quinone reductase in Hepa 1c1c7 cells over broccoli
      cultivars, due to both an increase in 4-methylsulphinylbutyl glucosinolate
      content and increased percentage conversion to sulphoraphane.

PMID- 9600345
TI  - Inhibition of growth and induction of apoptosis in human cancer cell lines by tea
      polyphenols.
AB  - In order to study the biological activities of tea preparations and purified tea
      polyphenols, their growth inhibitory effects were investigated using four human
      cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation
      after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate
      (EGCG) and (-)-epigallocatechin (EGC) displayed strong growth inhibitory effects
      against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22
      microM, but were less effective against lung cancer cell line H441 and colon
      cancer cell line HT-29 with IC50 values 2- to 3-fold higher. (-)-Epicatechin-3
      gallate, had lower activities, and (-)-epicatechin was even less effective.
      Preparations of green tea polyphenols and theaflavins had higher activities than
      extracts of green tea and decaffeinated green tea. The results suggest that the
      growth inhibitory activity of tea extracts is caused by the activities of
      different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or
      theaflavins for 24 h led to the induction of apoptosis as determined by an
      annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%,
      respectively; with 100 microM of these compounds, the apoptosis indices were 82,
      76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose
      dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a
      manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells
      was completely inhibited by exogenously added catalase (50 units/ml). These
      results suggest that tea polyphenol-induced production of H2O2 may mediate
      apoptosis and that this may contribute to the growth inhibitory activities of tea
      polyphenols in vitro.

PMID- 9600346
TI  - Disturbance of DNA damage recognition after UV-irradiation by nickel(II) and
      cadmium(II) in mammalian cells.
AB  - Nickel(II) and cadmium(II) have been shown previously to inhibit the incision
      step of nucleotide excision repair. By applying a gel-mobility-shift assay and
      HeLa nuclear extracts the effect of both metals on the damage recognition step of
      the repair process was investigated. Two proteins of 34 and 40 kDa were
      identified that bind with high affinity to a UV-irradiated synthetic
      oligonucleotide. When applying nuclear extracts from HeLa cells treated with 50
      microM nickel(II) and higher, there was a dose-dependent decrease in protein
      binding; this effect was largely reversible by the addition of magnesium(II) to
      the binding reaction. In the case of cadmium(II), a dose-dependent inhibition of
      DNA-protein interactions was detected at 0.5 microM and higher, which was almost
      completely reversible by the addition of zinc(II). Therefore, compounds of both
      metals disturb DNA-protein interactions essential for the initiation of
      nucleotide excision repair most likely by the displacement of essential metal
      ions.

PMID- 9600347
TI  - Genotoxicity of propoxur and its N-nitroso derivative in mammalian cells.
AB  - N-Nitroso propoxur (NP) can be synthesized from a widely used N-methylcarbamate
      insecticide, propoxur, in vitro in the laboratory. Because of the extensive use
      of aerosol propoxur, the adverse effect on cells of respiratory origin is worth
      elucidating. In this report, two mammalian cell cultures from respiratory tissues
      [a hamster lung fibroblast, V79, and a primary rat tracheal epithelial cell
      (RTE)], were used to investigate the genotoxicity of propoxur and NP. NP was more
      cytotoxic than propoxur, with LC50s (20 and six times smaller, respectively in
      V79 and RTE cells. NP significantly induced sister chromatid exchange (> or =
      0.01 microg/ml), chromosome aberration (> or = 2.5 microg/ml) and hprt gene
      mutation (> or = 0.5 microg/ml) in V79 cells, and cell transformation (> or = 0.2
      microg/ml) in RTE cells. Results of chromosome aberration and hprt gene mutation
      indicated that the major pre-mutagenic lesion induced by NP must be the O6
      methylguanine adduct, which frequently mispairs with thymine and thus gives rise
      to a GC-->AT transition. Propoxur was not mutagenic to either type of cells.
      However, it inhibited gap-junctional intercellular communication in V79 cells,
      which indicates that propoxur could act through some epigenetic mechanisms, such
      as tumor promotion or cell proliferation, in the multiple process of chemical
      carcinogenesis.

PMID- 9600348
TI  - Liver-specific catalase expression in transgenic mice inhibits NF-kappaB
      activation and DNA synthesis induced by the peroxisome proliferator ciprofibrate.
AB  - Peroxisome proliferators are a group of non-genotoxic hepatic carcinogens that
      have been proposed to act by increasing oxidative damage in the liver. To test
      this hypothesis, we have examined if hepatic catalase overexpression in
      peroxisome proliferator-treated mice influences the induction of cell
      proliferation or the activation of transcription factors involved in cell
      proliferation. Transgenic mice or non-transgenic littermates were fed either
      0.01% ciprofibrate or a control diet for 21 days. Fatty acyl CoA oxidase activity
      was not significantly affected by catalase overexpression, although the ratio of
      fatty acyl CoA oxidase to catalase was significantly decreased in transgenic
      animals. The labeling index in hepatocytes was significantly increased by
      ciprofibrate in non-transgenic mice, but catalase overexpression significantly
      inhibited this increase. Ciprofibrate increased the activation of nuclear factor
      (NF)-kappaB in non-transgenic mice, but this increase was inhibited by catalase
      overexpression. Ciprofibrate also increased AP-1 activation, but catalase
      overexpression did not significantly inhibit this increase, although AP-1
      activation was 40% lower in transgenic mice. These results support the hypothesis
      that active oxygen plays a role in the induction of cell proliferation by the
      peroxisome proliferator ciprofibrate and therefore may be important in the
      carcinogenicity of these agents.

PMID- 9600349
TI  - Synthesis of fjord region tetraols and their use in hepatic biotransformation
      studies of dihydrodiols of benzo[c]chrysene, benzo[g]chrysene and
      dibenzo[a,l]pyrene.
AB  - Metabolic activation of the racemic benzo[c]chrysene-trans-9,10-,
      benzo[g]chrysene-trans-11,12- and dibenzo[a,l]pyrene-trans-11,12-dihydrodiols to
      fjord region syn- and anti-dihydrodiol epoxides by microsomes of Aroclor 1254
      treated Sprague-Dawley rats has been examined. Since the fjord region dihydrodiol
      epoxides were hydrolytically unstable under the experimental conditions, their
      enzymatic formation was determined by analyzing the tetraols as their products of
      acidic hydrolysis upon addition of perchloric acid. The various stereoisomeric
      tetraols formed were separated by HPLC and identified by co-chromatography with
      authentic tetraols, which had been prepared by acidic hydrolysis of synthetically
      available syn- and anti-dihydrodiol epoxides and characterized by NMR and UV
      spectroscopy. Under standardized conditions the acidic hydrolysis of syn
      dihydrodiol epoxides of benzo[c]chrysene, benzo[g]chrysene and dibenzo[a,l]pyrene
      resulted in the formation of two tetraols with cis/trans ratios of 81:19, 77:23
      and 80:20, respectively, whereas the anti-dihydrodiol epoxides underwent almost
      exclusively trans hydrolysis. The proportion of the stereoisomeric tetraols
      obtained from microsomal incubations indicates that all three dihydrodiols are
      predominantly oxidized at the adjacent olefinic double bond to the anti
      diastereomers of the corresponding fjord region dihydrodiol epoxides accounting
      for 4-35% of the ethyl acetate-extractable metabolites. To allow quantitative
      assessment of the metabolites 3H-labeled trans-dihydrodiols were synthesized by
      reduction of the corresponding o-quinones with sodium borotritide. Metabolic
      conversion of benzo[c]chrysene-trans-9,10- and dibenzo[a,l]pyrene-trans-11,12
      dihydrodiol by rat liver microsomes were in a similar low range during the first
      10 min of incubation (6.2 +/- 1.2 and 3.4 +/- 1.0 nmol substrate/nmol cytochrome
      P450/10 min, respectively), whereas the conversion of benzo[g]chrysene-trans
      11,12-dihydrodiol was much higher (20.6 +/- 2.2 nmol substrate/nmol cytochrome
      P450/10 min). Given the strong intrinsic mutagenic and carcinogenic activity of
      the fjord region dihydrodiol epoxides, our data indicate that their formation,
      even at a relatively low level, may contribute significantly to the biological
      activity of the parent hydrocarbons.

PMID- 9600350
TI  - Inhibition of ultraviolet B (UVB)-induced c-fos and c-jun expression in vivo by a
      tyrosine kinase inhibitor genistein.
AB  - We reported the inhibitory effects of genistein, an inhibitor of tyrosine protein
      kinase (TPK), on ultraviolet B (UVB)-induced expression of c-fos and c-jun in
      SENCAR mouse skin. UVB irradiation substantially increased transcript levels of c
      fos and c-jun mRNA in mouse skin. Topical application of genistein 60 min before
      UVB radiation reduced c-fos and c-jun expression in the mouse skin in dose
      dependent manner. Inhibition was more pronounced in skin exposed to the low dose
      (5 kJ/m2) than to the high dose (15 kJ/m2) of UVB radiation. In addition,
      genistein exhibited more inhibition of c-fos than that of c-jun. Post-application
      of genistein after UVB exposure down-regulated the expressions of c-fos and c
      jun, but to a lesser extent compared with pre-application. A431 human epidermoid
      carcinoma cells, which excessively express epidermal growth factor receptors (EGF
      R), were used to investigate the possible mechanism of genistein's action. The
      results showed that genistein down-regulated the UVB-mediated phosphorylation of
      TPK-dependent EGF-R in a dose-dependent manner. We concluded that inhibition of
      UVB-induced c-fos and c-jun expression in mouse skin by genistein may, at least
      in part, result from the inhibition of TPK activities and down-regulation of EGF
      R phosphorylation. Suppression of UVB-induced proto-oncogene expression in mouse
      skin suggests that genistein may serve as a potential preventative agent against
      photodamage and photocarcinogenesis.

PMID- 9600351
TI  - Effect of cigarette smoke on CYP1A1, CYP1A2 and CYP2B1/2 of nasal mucosae in F344
      rats.
AB  - Enzymes of the nasal tissue, one of the first tissues to contact inhaled
      toxicants, are relatively resistant to induction by traditional inducers. Because
      tobacco smoke has been shown to induce cytochrome P450 1A1 (CYP1A1) in rat and
      human lung tissue, we hypothesized that it would also alter levels of xenobiotic
      metabolizing enzymes in nasal mucosae. In the present study, the effect of
      mainstream cigarette smoke (MCS) on nasal CYP1A1, CYP1A2 and CYP2B1/2 was
      explored. Four groups of 30 F344 rats were exposed to MCS (100 mg total
      particulate matter/m3) or filtered air for 2 or 8 weeks. Western analysis of
      microsomes from nasal tissue of MCS-exposed rats showed an induction of CYP1A1 in
      respiratory and olfactory mucosae, as well as liver, kidney and lung. Relative to
      controls, CYP1A2 levels increased slightly in the liver and olfactory mucosa.
      CYP2B1/2, which increased in the liver, appeared to decrease in upper and lower
      respiratory tissues. Little to no immunoreactivity with CYP1A1 antibody was
      observed in fixed nasal sections of control rats, yet intense immunoreactivity
      was seen in epithelia throughout the nasal cavity of MCS-exposed rats.
      Ethoxyresorufin O-deethylase activity (associated with CYP1A1/2) decreased
      approximately 2-fold in olfactory mucosa, but increased in non-nasal tissues of
      rats exposed to MCS. Methoxy- and pentoxyresorufin O-dealkylase activities
      (associated with CYP1A2 and CYP2B1/2, respectively) decreased in olfactory and
      respiratory mucosae, as well as lung (CYP2B1/2), yet increased in liver. These
      data suggest that xenobiotic-metabolizing enzymines of the nasal mucosae may be
      regulated differently than other tissues.

PMID- 9600352
TI  - Potentiating effect of dietary vitamin A on photocarcinogenesis in hairless mice.
AB  - Vitamin A and its derivatives (retinoids) exert modulatory effects on epithelial
      differentiation and are used therapeutically against skin cancers, but the role
      of dietary vitamin A in ultraviolet (UV)-induced carcinogenesis is far from
      clear. To study this process, 220 hairless mice were given diets containing low
      (0.3-0.6 mg/kg; A-) or high (4-6 mg/kg; A+) amounts of retinol, which resulted
      after 2 months in an approximately 4-fold difference in liver and skin vitamin A
      levels as determined by HPLC. Commencing after 1 month of diet, daily
      irradiations with UVB (280-320 nm) or UVAB (280-380 nm) were given to 176 of the
      animals for 18 weeks (cumulative doses of UVB and UVA: 26 J/cm2 and 168 J/cm2,
      respectively). The first skin tumours, known to be squamous cell carcinomas,
      appeared after 35 weeks in the UVAB-irradiated A+ animals and 5-6 weeks later in
      the other groups. After one year the frequency of tumour-bearing animals was 49
      63% in the A+ groups and 28-39% in the A- groups (P = 0.003). Two months later
      the corresponding figures were 66-72% and 50-53%, respectively (P = 0.014).
      Disregarding the effect of dietary vitamin A, there was no difference in the
      final tumour incidence between UVB- and UVAB-irradiated animals. The epidermal
      vitamin A content at 72 h post-irradiation was approximately 60% lower in A+
      animals and approximately 10% lower in A- animals compared with the non
      irradiated controls. Rather than protecting against skin cancer, a diet rich in
      vitamin A seems to facilitate UV carcinogenesis in hairless mice. A possible
      explanation is that photodecomposition of excessive vitamin A generates short
      lived intermediates that may act as photosensitizers during cutaneous
      carcinogenesis.

PMID- 9600353
TI  - Characterization of xenobiotic-metabolizing enzymes and nitrosamine metabolism in
      the human esophagus.
AB  - Esophageal cancer has been associated with tobacco smoking, and nitrosamines are
      possible causative agents for this cancer. The present study investigated the
      metabolism of the tobacco carcinogens N'-nitrosonornicotine (NNN), 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosodimethylamine
      (NDMA), as well as the presence of xenobiotic-metabolizing enzymes in human
      esophageal tissues from individuals in the United States and Huixian, Henan
      Province, China (a high-risk area for esophageal cancer). All esophageal
      microsomal samples activated NNN and the metabolic rate was 2-fold higher in the
      esophageal samples from China than the USA. All microsomal samples activated
      NDMA. However, most of the microsomal samples did not activate NNK.
      Troleandomycin (an inhibitor of cytochrome P450 3A) decreased the formation of
      NNN-derived keto acid by 20-26% in the esophageal microsomes. The activities for
      NADPH: cytochrome c reductase, ethoxycoumarin O-deethylase, NAD(P)H: quinone
      oxidoreductase and glutathione S-transferase were present in the esophageal
      samples. Coumarin 7-hydroxylase (a representative activity for P450 2A6) activity
      was not detected in the esophageal microsomal samples. The activities for
      nitrosamine metabolism and xenobiotic-metabolizing enzymes were decreased (by 30
      50%) in the squamous cell carcinomas compared with their corresponding non
      cancerous mucosa. The presence of activation and detoxification enzymes in the
      esophagus may play an important role in determining the susceptibility of the
      esophagus to the carcinogenic effect of nitrosamines. Our results suggest that
      P450s 3A4 and 2E1 are involved in the activation of NNN and NDMA, respectively,
      in the human esophagus.

PMID- 9600354
TI  - A human vascular endothelial cell model to study angiogenesis and tumorigenesis.
AB  - Endothelial cell biology has recently been the subject of considerable interest
      in thrombosis and cancer research. However, the successful establishment of
      immortalized human endothelial cells which retain differentiated cell
      characteristics has been rare. We have successfully established immortalized
      human umbilical vein endothelial cells (HUVECs) by human papilloma virus (HPV)-16
      E6-E7. HPV-16 E6, E7 and E6-E7 were successfully introduced into HUVEC cells.
      Both E6 and E7 cultures had an extended lifespan but eventually underwent
      senescence. E6-E7 cultures 4-5-2G, however, acquired an indefinite lifespan in
      culture but did not undergo malignant conversion. Telomerase activity was not
      detected in either E6 or E7 cultures; however, telomerase was detected in E6-E7 4
      5-2G cells. The cells exhibited a 'cobblestone' morphology and developed a
      capillary-like tube structure upon reaching confluence. The 4-5-2G line expressed
      Factor VIII related antigen and took up DiI-Ac-LDL as markers of endothelial
      origin. The line expressed integrin subunits (alpha(v)beta3, alph(v)beta5, beta1,
      alpha2, alpha3, beta4 and alpha6) consistent with an endothelial origin. The
      higher passage of 4-5-2G line showed a similar intensity of integrin
      immunostaining to that of primary HUVECS. Subsequent infection of these immortal
      cells with the Kirsten murine sarcoma virus which contains an activated K-ras
      oncogene induced morphological transformation that led to the acquisition of
      invasion capability and neoplastic properties. Telomerase was also detected in
      the tumorigenic v-Ki-ras transformed cell line. These cell lines should be useful
      for studies of the molecular mechanisms underlying normal and neoplastic
      endothelial cell proliferation and migration, and might also provide an in vitro
      model for development of pharmacologic and gene therapy for cardiovascular
      thrombosis and cancer.

PMID- 9600355
TI  - Altered gene expression in a clonal epidermal cell model of carcinogenesis
      identified by RNA differential display.
AB  - We have developed a multistage model system in which a normal mouse keratinocyte
      clone has been initiated with 7,12-dimethylbenz[a]anthracene and variant clones
      derived with benign or malignant phenotypes. To identify specific genes altered
      during mouse skin carcinogenesis, the gene expression patterns of the normal
      parental epidermal cell, an initiated cell, a benign papilloma, and a poorly
      differentiated squamous cell carcinoma were compared using RNA differential
      display. Most alterations in gene expression were observed at malignant
      conversion, that is, in the poorly differentiated squamous cell carcinoma that is
      known to have deregulated expression of p53. The sequence of a cloned cDNA
      fragment lost in the poorly differentiated squamous cell carcinoma was nearly
      identical to the 3' region of an adhesion-related kinase which is involved in
      homophilic cell aggregation. It is found in normal epidermal progenitor cells as
      well as tumorigenic cells with differentiation potential, but not in tumorigenic
      cells with a poorly differentiated phenotype, suggesting that this adhesion
      related kinase may be involved in epidermal cell differentiation. Differential
      display within the cloned epidermal cell model appears to be useful in detecting
      and identifying malignant conversion-associated genes which then can be tested
      directly for their potential role in epithelial carcinogenesis.

PMID- 9600356
TI  - Inhibition of vinyl carbamate-induced hepatotoxicity, mutagenicity, and
      tumorigenicity by isopropyl-2-(1,3-dithietane-2-ylidene)-2-[N-(4-methylthiazol-2-
      yl)carbamoyl]acetate (YH439).
AB  - Isopropyl-2-(1,3-dithietane-2-ylidene)-2-[N-(4-methylthiazol -2
      yl)carbamoyl]acetate (YH439) is a novel dithioylidene malonate derivative
      developed for the treatment of hepatic injury. The compound has been found to
      down-regulate the expression of hepatic cytochrome P-450 2E1 (CYP2E1) at the
      transcriptional level (8). Certain organosulfur compounds present in garlic
      elicit protective effects on chemically induced carcinogenesis and mutagenesis
      and their chemopreventive activities are associated in part with inhibition of
      CYP2E1. As part of a program to determine the likely chemopreventive potential of
      YH439, we initially examined its effects on hepatotoxicity induced by vinyl
      carbamate (VC), a proximate carcinogen that is preferentially bioactivated by
      CYP2E1. A single i.p. injection of VC (125 mg/kg body wt) to male Sprague-Dawley
      rats resulted in severe hepatic lesions as demonstrated by elevated levels of
      serum enzymes such as alanine aminotransferase and aspartate aminotransferase.
      Histopathological evaluation of liver sections from VC-treated animals revealed
      that the hepatic damage mainly consisted of centrilobular necrosis with
      sinusoidal congestion. Oral administration of YH439 (200 mg/kg body wt) to male
      Sprague-Dawley rats 2 days, 1 day and 4 h prior to VC completely prevented the
      hepatic damage caused by this carcinogen. In another experiment, rat hepatic
      microsome-mediated bacterial mutagenicity of VC was suppressed by YH439 in a dose
      related manner. Furthermore, pretreatment of female CD-1 mice with YH439 by
      gastric intubation resulted in diminution of VC-induced skin carcinogenesis.

PMID- 9600358
TI  - Effects of smoking and aging on oxidative DNA damage of human lymphocytes.
AB  - The effects of H2O2-induced oxidative DNA damage in 80 healthy individuals with
      relation to age (20-25 and 55-60 years old) and smoking has been investigated
      with the comet assay technique. Both factors have shown a significant effect upon
      basal DNA damage with smoking appearing to have the most impact. A
      differentiation of the four groups response to induced oxidative damage was also
      observed. A distinctly separate behavior of the younger non-smokers group, when
      compared with the rest of the categories, was found. This is attributed to the
      lower degree of initial basal damage that occurs in their lymphocytes.

PMID- 9600357
TI  - hMLH1 and hMSH2 expression and BAX frameshift mutations in ovarian cancer cell
      lines and tumors.
AB  - The expression of mismatch repair proteins hMSH2 and hMLH1 was investigated in
      human ovarian cancer cell lines and in biopsies of ovarian carcinomas obtained
      from 20 patients undergoing surgical operation. By Western blotting analysis
      hMSH2 protein was detected in all the tumor samples analyzed and in eight out of
      nine human ovarian cancer cell lines, while hMLH1 was undetectable in four out of
      20 ovarian tumors and in five out of nine human ovarian cancer cell lines
      analyzed. The possible presence of frameshift mutations in the BAX gene, which
      contains a sequence of eight contiguous guanines in its third exon, was tested in
      all the samples. All the cell lines presented the normal alleles for the BAX gene
      while only in one of the tumor samples a heterozygous frameshift mutation was
      found. The frameshift mutation was associated to a low, almost undetectable,
      level of BAX protein which was instead present at much higher levels in all the
      other samples investigated. The results indicate that frameshift mutations in the
      BAX gene, possibly arising as a consequence of microsatellite instability
      (detectable in these tumors), is detectable in human ovarian cancer although
      quantitatively it does not appear to be a major determinant of the low apoptotic
      response to chemotherapy observed in ovarian cancer cells.

PMID- 9600359
TI  - Insulin does not promote rat mammary carcinogenesis.
AB  - Indirect evidence from both epidemiological studies and animal experiments
      suggests that insulin may promote breast cancer development. In this study, we
      directly tested for a promoting effect of insulin on mammary carcinogenesis in
      Sprague-Dawley rats. Fifty day-old female rats received an i.p. injection of 37.5
      mg/kg methylnitrosourea (MNU). Five days later, the animals were randomized into
      two groups. One group received insulin injections five times/week until the time
      of death, while the other control group received similar injections of normal
      saline. Over the course of 26 weeks following MNU treatment, the mammary tumour
      incidence in the insulin-treated group did not differ significantly from the
      saline-treated controls. Furthermore, the number of tumours per tumour-bearing
      rat did not differ between groups. Our results demonstrate that insulin is not a
      promoter of mammary carcinogenesis in this model.

PMID- 9600360
TI  - Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung
      tumorigenesis by dietary olive oil and squalene.
AB  - Epidemiological studies have suggested that frequent olive oil consumption may be
      a protective factor against lung cancer formation. Squalene, a characteristic
      compound in olive oil, is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase activity and has been proposed to inhibit the farnesylation of ras
      oncoproteins. The present study investigated the effect of dietary olive oil and
      squalene in a mouse lung tumorigenesis model. Female A/J mice were fed AIN-76A
      diets containing 5% corn oil (control), 19.6% olive oil, or 2% squalene starting
      at 3 weeks before a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) (103 mg/kg, i.p.). Animals were maintained on their respective diets
      throughout the study. At 16 weeks after NNK administration, 100% of the mice in
      the control group had lung tumors with a tumor multiplicity of 16 tumors per
      mouse. The olive oil and squalene diets significantly (P < 0.05) decreased the
      lung tumor multiplicity by 46 and 58%, respectively. The squalene diet
      significantly (P < 0.05) decreased lung hyperplasia by 70%. In mice fed a diet
      containing 2% squalene for 3 weeks, the activation of NNK was increased by 1.4-
      and 2.0-fold in lung and liver microsomes, respectively, but its relationship to
      the inhibition of carcinogenesis is not clear. These results demonstrate that
      dietary olive oil and squalene can effectively inhibit NNK-induced lung
      tumorigenesis.

PMID- 9600361
TI  - Celiac sprue presenting during the puerperium: a report of three cases and a
      review of the literature.
AB  - We present three patients in whom there was an acute presentation of
      malabsorption in the puerperium and in whom the final diagnosis was celiac sprue.
      The reason for the dramatic increase in the symptoms after delivery, as well as
      the absence of symptoms before this, is unclear but may be related to immunologic
      changes that occur during pregnancy.

PMID- 9600362
TI  - Melanosis coli in inflammatory bowel disease.
AB  - Melanosis coli is a relatively common condition in which pigment is deposited in
      macrophages in the colonic lamina propria. The association with anthraquinone
      laxatives is well described, but melanosis coli has also been described in
      patients not using these agents. We report 25 patients with inflammatory bowel
      disease and melanosis coli, 5 (20%) of whom had documented laxative use. Most
      patients had ulcerative colitis (72%) or Crohn's colitis (24%), and the mean
      duration of inflammatory bowel disease was more than 7 years. These data raise
      the possibility that chronic colitis could cause melanosis coli even in the
      absence of laxative use.

PMID- 9600363
TI  - Development of flat adenoma and superficial rectal cancer after pelvic radiation.
AB  - Little is known about the early development of rectal cancer in patients with
      radiation-induced colitis. We describe two patients with a history of radiation
      colitis who developed rectal cancer. The macroscopic appearance of these lesions
      suggested that they arose de novo, but the histologic findings were more
      consistent with progression along the adenoma-to-carcinoma sequence, a hybrid of
      de novo lesion and adenoma. Early rectal cancer associated with chronic
      inflammation should be considered if a nonpolypoid adenomatous lesion is detected
      in a patient who has received pelvic radiation.

PMID- 9600364
TI  - Anorectal manometric characteristics in men and women with idiopathic fecal
      incontinence.
AB  - To characterize and compare the anorectal manometric findings of men and women
      with idiopathic fecal incontinence referred to a tertiary care center for pelvic
      floor disorders, we reviewed 86 consecutive patients who underwent anorectal
      manometry during a 13-month period. We determined the etiologies of all patients
      and analyzed men and women with no obvious cause (idiopathic). The manometric
      parameters included resting and squeeze anal canal pressures, duration of squeeze
      pressures, threshold of external anal sphincter contraction, threshold of rectal
      sensation, and rectal compliance. Thirty-one of 86 patients were classified as
      having idiopathic fecal incontinence. The mean age of the 7 male patients with
      idiopathic fecal incontinence was 65 years, (range, 45-78 years) and 63 years
      (range, 38-83 years) in the 24 women. Compared with male patients, female
      patients had lower sphincteric pressures and shorter squeeze durations. Both men
      and women frequently exhibited poor phasic response of the external anal
      sphincter to rectal distention. We conclude that, compared with men, women with
      idiopathic fecal incontinence more often exhibit abnormalities of anal
      sphincteric motor function. The sex-related differences in muscle mass and past
      traumatic events related to childbirth may partly account for these findings.

PMID- 9600365
TI  - Distribution of lymph node metastasis and level of inferior mesenteric artery
      ligation in colorectal cancer.
AB  - To investigate the distribution of lymph node metastasis along the inferior
      mesenteric artery (IMA) and clarify whether high ligation of the IMA is important
      or not, we examined the surgical results of 172 patients with cancer of the
      sigmoid colon and rectum. Histologically, lymph node metastasis was absent in 108
      (63%) patients and present in 64 (37%) patients. The distribution was adjacent to
      the wall of the rectum (35.5%) and sigmoid colon (10.5%), along the IMA (7.7%)
      and sigmoid colic artery (6.3%), and at the root of the IMA (0.7%, 1 of 135
      patients). The presence of lymph node metastasis was predicted by the operative
      findings of lymph node metastasis (p < 0.01) and serosal invasion (p < 0.05) and
      by the histologic type of tumor (p < 0.05). These results indicate that lymph
      node metastasis at the root of the IMA is rare, and complete removal of the
      pericolic and intermediate nodes (D2 dissection) without high ligation of the IMA
      is feasible for cancer of the sigmoid colon and rectum.

PMID- 9600366
TI  - Ischemic hepatitis: clinical and laboratory observations of 34 patients.
AB  - Ischemic hepatitis, a relatively infrequent disorder occurring in 0.16% to 0.50%
      of patients admitted to medical intensive care units, often follows episodes of
      hypotension or acute heart failure. Investigating the clinical characteristics of
      patients with ischemic hepatitis may add to our understanding of the pathogenesis
      and significance of this syndrome. We therefore conducted a retrospective
      analysis of 34 patients to examine the possible contribution of the various
      baseline characteristics to the severity of the hepatic damage. In all patients
      liver disease was unexpected and in some, liver dysfunction dominated the
      clinical picture. All patients had high serum glutamic pyruvic transaminase
      (SGPT) and lactic dehydrogenase (LDH) levels (mean +/- SE, 2073 +/- 255
      international units and 6085 +/- 748 international units, respectively). The mean
      SGPT/LDH ratio was 0.34. Most patients had coagulopathy with a prolonged
      prothrombin time (mean +/- SE, 5.86 +/- 1.37 international normalized ratio
      [INR]). The most common diagnosis on admission was respiratory distress secondary
      to various causes. Before the development of the hepatic dysfunction, respiratory
      failure and hypoxemia were observed in 68% of the patients, whereas hypotension
      was observed in only 38%. More than 90% of the patients had three or more
      associated comorbid conditions. The most frequent of these were left heart
      failure (88.2%), right heart failure (67.6%), chronic obstructive lung disease
      (58.8%), and chronic renal failure (55.9%). During the acute episode, more than
      90% of the patients had transient deterioration of their renal functions.
      Hypoglycemia was noted in 11 patients (32.4%), and the glucose level was
      inversely correlated with the SGPT level (r = -0.43, p = 0.01). Stepwise multiple
      regression analysis showed that left heart failure, systolic blood pressure lower
      than 90 mm Hg, and female gender, together, accounted for 34% of the variance of
      the peak SGPT levels (p = 0.002). Fourteen (41.2%) patients died during the 3
      month follow-up period, but none from the hepatic injury. None of the clinical or
      laboratory parameters measured predicted mortality. Clearly, ischemic hepatitis
      is associated with a high risk of death. The characteristic patients are those
      with multiple underlying systemic diseases and conditions, especially those with
      left heart failure. Liver function test results and levels of liver enzymes
      should be monitored in these patients, particularly when they are admitted for
      respiratory deterioration and episodes of hypotension.

PMID- 9600367
TI  - Chronic unexplained liver disease in children with primary immunodeficiency
      syndromes.
AB  - Liver disease may be found in patients with primary immunodeficiency syndromes
      because of the high risk of infection with hepatotropic viruses related to the
      treatment with blood derivatives. The prevalence of liver disease in these
      patients and its etiology, however, is still not completely understood. We have
      evaluated the prevalence and the etiology of liver disease in children with
      different forms of primary immunodeficiencies. Thirty patients included in the
      study underwent molecular studies to detect common hepatotropic viruses,
      including hepatitis C and G viruses. Liver involvement was found in 11 of 30
      (36.6%) patients. All patients with liver disease had deficiencies of specific
      immunity, with a prevalence in this subgroup of 47.8%. Liver disease was more
      severe in patients with T and B cell combined immune disorders than in those with
      a selective T cell immunodeficiency. Moreover, the severity of the disease
      correlated with an overall more rapid fatal outcome. A viral etiology was found
      in only six of these patients, whereas in the remaining five patients, no cause
      of liver injury was identified. In the virally infected patients, hepatitis C
      virus was the most common viral agent. In patients with immunodeficiencies, there
      is a high prevalence of liver disease not fully explained on the basis of the
      common viral infections.

PMID- 9600368
TI  - Hepatitis C viral RNA status at two weeks of therapy predicts the eventual
      response.
AB  - We investigated the timing of the disappearance and reappearance of serum
      hepatitis C viral (HCV) RNA in patients with chronic hepatitis C during
      interferon treatment and follow-up. Serum samples were tested for HCV RNA by
      polymerase chain reaction in 62 patients with chronic hepatitis C treated with
      interferon-alpha for 24 weeks. We found that 17 patients obtained complete
      response, with absence of serum HCV RNA for 6 months after the treatment. Twenty
      nine patients had a partial response, with reappearance of serum HCV RNA within 6
      months of follow-up, and 16 patients were nonresponders who were positive for
      serum HCV RNA throughout the observation period. HCV RNA disappeared within 2
      weeks of treatment in 31 patients, including all 17 (100%) complete responders
      and 14 (48.3%) of the 29 partial responders. The patients remaining positive for
      HCV RNA at the second week were 15 (51.7%) of the 29 partial responders and the
      16 nonresponders. In all of the 29 partial responders, viremia recurred within 1
      month after the treatment. These results indicate that the status of HCV RNA at
      the second week of treatment is a useful predictor of effective treatment,
      whereas status at the first month after cessation of treatment is useful for
      assessing the effectiveness of interferon itself.

PMID- 9600369
TI  - Tamoxifen does not improve survival of patients with advanced hepatocellular
      carcinoma.
AB  - To discover whether tamoxifen is able to extend the survival of patients with
      advanced hepatocellular carcinoma, we included 80 patients with cirrhosis and
      advanced hepatocellular carcinoma in a multicenter, double-blind, placebo
      controlled trial in order to analyze the influence of treatment with tamoxifen on
      survival. The patients were randomized to receive tamoxifen, 40 mg/day (group 1),
      or placebo (group 2). Both groups were similar in age, sex, etiology of
      cirrhosis, biochemical, hematologic and hormonal parameters, morphology of the
      tumor (nodular vs multinodular or massive), Child-Pugh's score, and Okuda's
      stage. The 1-year survival rate was similar in both groups (30% in group 1 vs
      37.8% in group 2; p = 0.31). Tamoxifen treatment was well tolerated by the
      patients. We conclude that tamoxifen does not extend the survival of patients
      with cirrhosis and advanced hepatocellular carcinoma.

PMID- 9600370
TI  - Alcoholic recidivism after liver transplantation for alcoholic cirrhosis.
AB  - Liver transplantation (LT) for alcoholic cirrhosis remains controversial. This
      controversy surrounding LT in alcoholics focuses on the risk of alcohol
      recidivism and on potential noncompliance with the immunosuppressive regimen,
      both of which result in graft failure. Our study examined alcohol recidivism
      after LT by measuring alcohol in urine and its repercussion on the allograft.
      Forty-four consecutive alcoholic patients and a comparison group of 17 patients
      receiving LT were included in this study and followed up for a mean of 39.5 +/-
      19.6 months. Seven percent (3 of 44) of patients with alcoholic liver disease and
      0% of patients in the comparison group admitted to having used alcohol after LT.
      Alcohol in urine, however, was detected in 18% (8 of 44) of the alcoholic group;
      therefore the true recidivism rate was higher than the rate admitted. All
      patients in both groups were compliant with the medications, because the
      cyclosporine levels were within the therapeutic range in all. On histologic
      examination the only alcohol-induced lesion found in three of the eight
      recidivistic patients was steatosis. Therefore, although alcoholic recidivism
      occurs, it does not seem to affect compliance to treatment profoundly or to
      compromise graft function. Therefore, LT seems justified for end-stage alcoholic
      cirrhosis.

PMID- 9600371
TI  - A-beta-lipoproteinemia: clinical and laboratory features, therapeutic
      manipulations, and follow-up study of three members of a Greek family.
AB  - We describe the clinicoepidemiologic features, natural history, and therapeutic
      manipulations in three Greek patients with A-beta-lipoproteinemia (two brothers
      aged 15 and 29 years, respectively, and one sister aged 30 years). Diarrhea
      started in infancy in the two brothers and from the age of 13 in the sister.
      During the second decade of life, central nervous system symptoms became
      prominent, with fatigue and disturbance in gait and balance. Night blindness
      developed at a later phase of the disease in the brothers, whereas cavus
      developed in both legs in the sister. Apolipoprotein B was absent in all
      patients, and each had more than 50% of acanthocytes present on peripheral smear.
      The diagnosis of A-beta-lipoproteinemia was established on the basis of small
      bowel histology and serum lipid estimations. Family studies revealed normal lipid
      profiles in all healthy members. The human leukocyte antigen (HLA) pattern in the
      two most severely affected patients was identical. The only detectable difference
      between the severely ill patients and other members of the family, however, was
      homozygosity for the HLA B18 antigen, whereas the third patient had no alleles
      for the HLA B18 antigen. Treatment consisted of a low-fat diet and high doses of
      vitamins A and E. A modified diet substituting medium-chain triglycerides for
      dietary fat was also given, with significant improvement in the nutritional
      status of patients but not in symptoms related to advanced disease, such as
      retinal and cardiac manifestations. We conclude that the course of the disease in
      untreated patients is characterized by continuous symptoms. Some of the symptoms,
      however, especially those related to malabsorption, as well as some
      anthropometric parameters can be improved by the application of a modified diet
      including medium-chain triglycerides. We suggest the routine measurement of
      plasma lipids and apoproteins not only in children with failure to thrive, with
      unexplained malabsorption, or with neurologic symptoms, but also in adults with
      chronic diarrhea accompanied by neurologic symptoms or clinical and laboratory
      signs of malabsorption.

PMID- 9600372
TI  - Colonic ulcers in a patient with hepatitis C virus-associated polyarteritis
      nodosa.
AB  - An elderly woman presented with abdominal discomfort, pulmonary infiltrates,
      acute renal failure, purpura, and massive hematochezia. Numerous colonic ulcers
      with underlying fibrinoid necrotizing arteritis were found in the colectomy
      specimen. Anti-hepatitis C virus (HCV) antibodies and HCV RNA were present in the
      serum. The diagnosis of HCV-associated polyarteritis nodosa was clear. This
      clinical presentation differs from the more commonly occurring vasculitis
      complicating HCV infection, which is of the leukocytoclastic type, and is
      associated with overt liver disease and cryoglobulinemia. In our patient, results
      of liver tests were normal, there was no cryoglobulinemia, and the vasculitis was
      of the fibrinoid necrotizing arteritis type. HCV-associated polyarteritis nodosa
      should be considered in the differential diagnosis of necrotizing fibrinoid
      arteritis even in a patient with normal liver function test results and in the
      absence of cryoglobulinemia.

PMID- 9600373
TI  - Cricopharyngeal dysfunction in a patient with achalasia.
AB  - A 64-year-old man had intense dysphagia and aspiration of 1 month's duration. The
      patient had lower esophageal sphincter (LES) achalasia and cricopharyngeal
      dysfunction, with generalized muscle weakness discovered by neurologic
      examination. Endoscopy showed no lesions of the mouth, pharynx, larynx, or
      esophagus. The diagnosis of achalasia was made by manometry. The LES did not
      relax with deglutition; the contractions in the esophageal body were
      nonperistaltic and of low amplitude; and the upper esophageal sphincter pressure
      did not decrease after deglutition. A scintigraphic study of the oral and
      pharyngeal phases of swallowing showed a mouth and pharyngeal retention of 90% of
      the volume swallowed.

PMID- 9600374
TI  - Failure to detect early recurrence of gastric cancer.
AB  - Early gastric cancer recurrence is sometimes difficult to diagnose even by
      protocols using imaging techniques and tumor markers. We report a gastric cancer
      recurrence diagnosed by the appearance of a Sister Mary Joseph's nodule that
      illustrates the lack of sensitivity of these methods. We also discuss the
      protocol we currently follow for these patients.

PMID- 9600375
TI  - Colonic disease in cirrhotic patients with portal hypertension: an endoscopic and
      clinical evaluation.
AB  - Fifty cirrhotic patients with portal hypertension but without colonic or systemic
      disease underwent lower gastrointestinal endoscopy in order to investigate the
      effects, if any, of portal hypertension on the colon. Fifty patients without
      liver or systemic disease, examined by colonoscopy because of irritable bowel
      syndrome in the same period served as controls. Rectosigmoid varices were
      observed in 34% of the cirrhotic patients and 2% of the controls. Hemorrhoids
      were observed in 70% of the cirrhotic patients and 48% of the controls. Multiple
      vascular-appearing lesions were found in 16% of the cirrhotic patients and 6% of
      the controls. Nonspecific inflammatory changes were noted in 10% of the cirrhotic
      patients and 4% of the controls. Simultaneous presence, in the same patient, of
      rectosigmoid varices, hemorrhoids, multiple vascular-appearing lesions, and
      nonspecific inflammatory changes, was observed in only five (10%) of the
      cirrhotic patients. We found polyps in 12% of the cirrhotic patients and 14% of
      the controls, and a malignant tumor in 4% of the cirrhotic patients. The patients
      with normal colonoscopic findings were 8% of the cirrhotic patients and 36% of
      the controls. All patients and controls were followed up for 1 year; there was no
      gastrointestinal hemorrhage among controls, whereas 34% of the cirrhotic patients
      had an upper gastrointestinal hemorrhage (88% from esophageal varices, 12% from
      the stomach) and 4% had a lower gastrointestinal hemorrhage (one from
      rectosigmoid varices and one from nonspecific inflammatory lesions). Colonic
      lesions were significantly more frequent in the cirrhotic patients (92%) than in
      the control group (64%); however, such lesions did not seem specific to the
      disease and were not statistically correlated with the degree of esophageal
      varices by Child's grading, the etiology of cirrhosis, or the bleeding risk from
      the lower gastrointestinal tract.

PMID- 9600376
TI  - Pseudomembranous colitis induced by diclofenac.

PMID- 9600377
TI  - Abdominal tuberculosis involving hepatic hilar lymph nodes.

PMID- 9600378
TI  - Improved culture methods to expand Schwann cells with altered growth behaviour
      from CMT1A patients.
AB  - A duplication of the gene for myelin protein PMP22 is by far the most common
      cause of the hereditary demyelinating neuropathy CMT1A. A role for PMP22 in cell
      growth in addition to its function as a myelin protein has been suggested because
      PMP22 is homologous to a gene specifically upregulated during growth arrest.
      Furthermore, transfected rat Schwann cells overexpressing PMP22 show reduced
      growth. In addition, abnormal Schwann cell differentiation has been described in
      nerve biopsies from CMT1A patients. To analyse whether the duplication of the
      PMP22 gene in CMT1A neuropathy primarily alters Schwann cell differentiation and
      to exclude nonspecific secondary responses, we improved human Schwann cell
      culturing. This allowed us long-term passaging of human Schwann cells with
      unchanged phenotype, assessed by expression of different Schwann cell markers.
      Subsequently we established Schwann cell cultures from CMT1A nerve biopsies. We
      find decreased proliferation of Schwann cells from different CMT1A patients in
      all passages. We also demonstrate PMP22 mRNA overexpression in cultured CMT1A
      Schwann cells. We conclude that decreased proliferation in cultured Schwann cells
      that carry the CMT1A duplication indicates abnormal differentiation of CMT1A
      Schwann cells. The identification of an abnormal phenotype of CMT1A Schwann cells
      in culture could possibly lead to an in vitro disease model.

PMID- 9600379
TI  - Expression of DSD-1-PG in primary neural and glial-derived cell line cultures,
      upregulation by TGF-beta, and implications for cell-substrate interactions of the
      glial cell line Oli-neu.
AB  - DSD-1-PG is a chondroitin sulfate proteoglycan with neurite-outgrowth promoting
      properties expressed during development and upon lesion of neural tissues which
      has been defined with the specific monoclonal antibody 473HD. Double
      immunofluorescence studies performed on primary cerebellar cultures document that
      the proteoglycan is expressed on the surface of immature glial cells and the
      neural cell line Oli-neu, a model of mouse oligodendrocyte progenitors.
      Biochemical and immunoprecipitation studies performed with biosynthetically
      labelled Oli-neu and primary neural cells demonstrated that DSD-1-PG is expressed
      in vitro as a proteoglycan of 1000 kD apparent Mr with two core glycoproteins of
      250 kD and 400 kD. In order to study the regulation of DSD-1-PG expression, an in
      vitro enzyme-linked immunosorbent assay based on Oli-neu and mAb 473HD was
      established. TGF-beta1-3 induced up-regulation of the proteoglycan, while various
      growth factors and cytokines did not significantly affect DSD-1-PG expression in
      both the supernatant and the extract of the culture monolayer. FACSCAN analysis
      suggested that the proteoglycan is upregulated on the surface of Oli-neu. Cell
      substrate adhesion assays revealed that this enhanced expression correlates with
      a selective reduction of adhesion to laminin, but not fibronectin or merosin,
      which could specifically be neutralized by antibodies to DSD-1-PG. We conclude
      that the proteoglycan contributes to the regulation of glial precursor
      interactions with the extracellular matrix.

PMID- 9600380
TI  - Epidermal growth factor receptor in proliferating reactive glia following
      transient focal ischemia in the rat brain.
AB  - Severe transient focal cerebral ischemia causes brain infarction with a strong
      glial reaction. We have studied whether postischemic reactive glial cells express
      epidermal growth factor receptor (EGFR) following middle cerebral artery
      occlusion in the rat. We have also looked for signs of proliferating activity, as
      EGFR is known to be involved in cell growth and proliferation in certain non
      neural cells. EGFR was studied using three different antibodies which were found
      to stain for a tyrosine-phosphorylated protein (p170) corresponding to the
      membrane-anchored EGFR. Neurons of the control brain were strongly immunoreactive
      to EGFR, but a decrease of EGFR-immunoreactivity was seen in the ipsilateral
      brain side from 24 h postischemia due to neuronal loss. However, the presence of
      abundant glial cells strongly immunoreactive to EGFR became apparent in this area
      from 4 days postischemia onward. The use of microglial (lectin or OX-42) and
      astroglial (GFAP) markers showed that these postischemic EGFR-stained cells were
      reactive microglia/macrophages and astroglia. The subcellular localization of
      EGFR in reactive microglia/macrophages was compatible with the network of the
      Golgi apparatus, as revealed with an antibody against a peripheral membrane-bound
      protein of the Golgi. The presence of abundant proliferating cells in the
      ischemic brain was detected from 4 days postischemia with an antibody against
      proliferating cell nuclear antigen. Proliferating reactive microglia/macrophages
      were abundant within the infarcted brain side, whereas proliferating astrocytes
      were found mainly in the immediate periphery of the infarct limiting the necrotic
      area from the undamaged tissue. These proliferating cells were immunoreactive to
      EGFR. The results show the presence of EGFR in postischemic reactive glial cells
      and suggest that EGFR-dependent pathways mediate signal transduction in reactive
      glia following transient focal cerebral ischemia.

PMID- 9600381
TI  - Genomic difference analysis by two-dimensional DNA fingerprinting reveals typical
      changes in human low-grade gliomas.
AB  - Cytogenetic and molecular analyses such as allelotyping studies have revealed
      several genetic changes typical for human glial neoplasms. However, most studies
      to date have involved malignant gliomas and thus are likely to reflect late
      events of tumor progression. To elucidate the initial events of glial tumor
      growth, we performed a genome-wide search for genetic alterations in the DNA of
      43 low-grade gliomas as compared to the constitutional DNA of the patients'
      peripheral blood leucocytes using the two-dimensional (2D) DNA fingerprint
      approach. Reliable results were obtained for 28 blood/tumor sample pairs (13
      astrocytomas, 9 pilocytic astrocytomas, 1 oligodendroglioma, 3 oligoastrocytomas,
      and 2 ependymomas). DNA was digested with the restriction enzyme HaeIII and the
      resulting fragments were separated on 2D gels according to size and sequence in
      the first and second dimensions, respectively. Patterns of hundreds of spots were
      generated by hybridization with four different mini- and microsatellite core
      probes. A total of 655 to 1,122 spots could be visualized per sample. Comparison
      of blood and tumor spot patterns revealed two to 11 reproducible changes per
      patient. Most of the differences were spot losses (77.1%), while the others
      appeared to be gains or amplifications. Exactly the same changes were found in
      tumor recurrences which lacked histological signs of progression. When comparing
      different patients, many of the affected spots tended to cluster in particular
      areas of the gel as revealed by computer-aided comparison of all spot patterns.
      Eleven different spot clusters were identified which may correspond to several
      major deletion targets. This study provides the basis for the future molecular
      cloning of the candidate tumor suppressor genes affected by the common spot
      losses and will allow new insights into the genetic mechanisms of glial
      tumorigenesis.

PMID- 9600382
TI  - Rapid clearance of tertiary butyl hydroperoxide by cultured astroglial cells via
      oxidation of glutathione.
AB  - The ability of astroglial cells to detoxify exogenously applied tertiary butyl
      hydroperoxide (tBHP) was tested using astroglia-rich primary cultures derived
      from the brains of newborn rats. If 200 microM tBHP was applied, this compound
      disappeared from the incubation buffer with an apparent half-life of about 5 min.
      After 20 min incubation tBHP was not detectable any more. A decay of tBHP was
      found even in the absence of cells. Therefore, half-times for the cell-dependent
      tBHP clearance were corrected for the cell-independent decay of tBHP. The cell
      dependent half-time of tBHP in the incubation buffer was found strongly elevated
      i) with increasing concentration of tBHP, ii) after decrease of the glutathione
      content of the cells by a preincubation with buthionine sulfoximine, an inhibitor
      of glutathione synthesis, iii) in the presence of mercaptosuccinate, an inhibitor
      of glutathione peroxidase, and iv) in the absence of glucose, the precursor for
      the generation of NADPH. Incubation of astroglial cells with 200 microM tBHP in
      the absence of glucose led to a 46% oxidation of the cellular glutathione within
      30 s. Under these conditions the cells were unable to restore the original high
      ratio of the concentrations of GSH to GSSG within 30 min of incubation. In
      contrast, if glucose was present the level of GSSG encountered on incubation with
      tBHP was lower (32% of total glutathione after 30 s) and the original ratio of
      the levels of GSH to GSSG was essentially reestablished within 10 min. In the
      presence of 3 mM mercaptosuccinate oxidation of glutathione was almost completely
      inhibited. These results demonstrate that an exogenous hydroperoxide is
      detoxified rapidly by astroglial cells via the glutathione system.

PMID- 9600383
TI  - Excitotoxic damage of retinal glial cells depends upon normal neuron-glial
      interactions.
AB  - Glutamate, the principal retinal neurotransmitter, can also act as a toxin when
      present in excessive concentrations as may occur in pathologies such as retinal
      ischemia or more generally in cerebral neuronal degenerative disease. As glial
      cells play pivotal roles in transfer of blood-borne molecules and in glutamate
      clearance, we investigated the effects of the excitatory amino acids glutamic and
      kainic acid on different in vitro preparations of retinal Muller glial cells.
      Glial viability or morphology were not influenced by excitatory amino acid
      exposure in either pure glial cultures or in monolayer cultures of mixed neonatal
      neurons and glia, whereas kainic acid specifically lysed amacrine cells in mixed
      or pure neuronal cultures. When retinal fragments were pre-incubated in
      excitatory amino acids prior to dissociation and seeding into culture, under
      these conditions Muller glial cells exhibited a dramatic loss of their normal
      epithelioid form to a retracted morphology. However, glial cell viability was not
      compromised, and rapid restoration of epithelioid in vitro glial morphology could
      be achieved by addition of exogenous epidermal and basic fibroblast growth factor
      to the culture medium. This study demonstrates that glial cells are structurally
      perturbed by excitotoxic conditions and that such effects are dependent on normal
      glial-neuronal interactions.

PMID- 9600384
TI  - Control of glial number: purification from mammalian brain extracts of an
      inhibitor of astrocyte division.
AB  - Inhibitors of astrocyte cell division, immunologically related to the sugar
      moiety of epidermal growth factor receptor and to blood group antigens, have been
      purified from mammalian brain extracts. Mass spectra, high resolution proton
      magnetic resonance spectra, and chemical and enzymic analysis of the purified
      fraction indicated that the compounds isolated were glycosphingolipids, although
      signals compatible with the presence of aminoacid residues were also observed.
      Lectin binding indicated the presence of NAc-Neuraminic acid, NAc-glucosamine,
      fucose, galactose, and glucose. The inhibitor was cytostatic for astrocytes, C6
      glioma cells, and endothelial cells, with approximate ID50 of 250 nM. Primary
      cultures of fibroblasts or 3T3 cells were not affected up to concentrations of
      800 nM. Concentrations of the inhibitor of 800 nM or higher, caused non-specific
      cytotoxicity. The biological and immunological properties of this brain inhibitor
      were identical to those of the EGF receptor-related inhibitor previously
      described with the acronym ERI. Because of its source and cytostatic action, the
      glial inhibitor has been renamed neurostatin. Rabbit antibodies to neurostatin
      immunostained astrocytes and neurons, both in culture and in tissue sections.

PMID- 9600385
TI  - HPC-7: a novel oligodendrocyte lineage protein which appears prior to
      galactocerebroside.
AB  - The identification of cell type-specific molecules expressed at different
      developmental stages can help to elucidate the regulatory mechanisms governing
      the survival, differentiation, and development of cells in the central nervous
      system (CNS). A cell surface protein, HPC-7, was detected on rat oligodendrocytes
      (OL) in culture by a monoclonal antibody generated against adult rat hippocampal
      membranes. Adult rat brain and sciatic nerve sections showed selective labeling
      of white matter and other myelinated fibers in both the CNS and peripheral
      nervous system (PNS). Double-labeling of secondary cultures of OL, O-2A, and type
      2 astrocytes and primary cultures of type-1 astrocytes with independent cell type
      specific antibodies confirmed that HPC-7 was expressed only by the OL lineage. By
      using a series of OL stage-specific antigenic markers (A2B5, 04, OL-1,
      galactocerebroside, myelin basic protein) HPC-7 was found to appear at the time
      when OL precursors became A2B5 negative and began their terminal differentiation
      in OL. On immunoblots, anti-HPC-7 antibody recognized a single 66 kDa band in rat
      OL and a single band at 100 kDa in adult myelin. N-glycosidase treatment showed
      that the HPC-7 protein did not contain substantial amounts of N-linked
      carbohydrate. Thus, HPC-7 appears to be a cell surface protein of the OL lineage
      that marks the important transition from proliferative precursor to postmitotic
      OL.

PMID- 9600386
TI  - Dopamine and N-methyl-D-aspartate receptor interactions in the neostriatum.
AB  - This review examines dopamine (DA) and glutamate receptor interactions in the
      neostriatum (NS) primarily from a neurophysiological perspective. Historically, a
      clear understanding of the function of DA in the NS has been difficult because it
      was considered a classical neurotransmitter with either excitatory or inhibitory
      actions and because many of the data were obtained by use of varying
      methodologies. When DA is considered a neuromodulator whose role is to alter how
      NS cells respond to glutamatergic inputs, many of its actions can be accounted
      for and predicted with great accuracy within a model of receptor subtype. In this
      model, DA via activation of D1 receptors potentiates responses mediated by
      activation of N-methyl-D-aspartate (NMDA) receptors. DA via activation of D2
      receptors attenuates responses mediated by activation of non-NMDA receptors.
      Outcomes of combinations of NMDA and D2 and non-NMDA and D1 receptors are not as
      predictable. The mechanisms underlying the D1-NMDA receptor interactions appear
      to involve alterations in cell excitability mediated by activation of Ca2+
      conductances and/or phosphorylation of NMDA receptors. Less is known about
      mechanisms underlying the D2-non-NMDA receptor interaction. The functional
      implications of this model in setting membrane potentials, signal-to-noise ratio,
      plasticity and excitotoxicity are discussed.

PMID- 9600387
TI  - The postnatal development of AMPA receptor subunits in the basal ganglia of the
      rat.
AB  - In situ hybridization and immunohistochemistry were used to characterize the
      expression pattern of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptors during postnatal development in the rat basal ganglia. All
      subunit transcripts showed some degree of developmental regulation. GluR1 and
      GluR2 are expressed at high levels in the neonate with reduced expression in the
      adult. GluR3 and GluR4 are expressed at significantly lower levels in both
      neonates and adults and have much more modest degrees of reduced expression in
      adults as compared with GluR1 and GluR2. Analysis of the flip and flop transcript
      isoforms indicates that GluR1 flip and flop and GluR2 flip are the predominately
      expressed splice variants in adults. Observed changes in the expression of the
      AMPA receptor transcripts indicate that there are fundamental differences in the
      expression of these receptor subunits in adults and neonates. This phenomenon may
      play a significant role in the establishment of proper synaptic circuitry within
      the developing basal ganglia in early postnatal life as well as contributing to
      differences in susceptibility to injury and disease in the aging brain.

PMID- 9600388
TI  - Prenatal exposure to neurotoxicants dieldrin or lindane alters tert
      butylbicyclophosphorothionate binding to GABA(A) receptors in fetal rat
      brainstem.
AB  - GABA acts as a trophic signal for cultured embryonic rat monoamine neurons by
      activating GABA(A) receptors. These effects are blocked by the organochlorine
      insecticide dieldrin and the classic GABA(A) antagonist bicuculline. Both
      dieldrin and another organochlorine insecticide, lindane, block the effects of
      GABA on the GABA(A) receptor by binding directly to the Cl- channel. Therefore,
      prenatal exposure to these chemicals could lead to disturbances in the trophic
      actions of GABA on monoamine neurotransmitter systems in the embryonic brain and
      produce alterations in GABA(A) receptor expression and function. Effects of daily
      prenatal exposure to organochlorine insecticide (dieldrin or lindane) or
      bicuculline from embryonic day (E)12-17 were determined in brains of E17 fetal
      rats using t-[35S]butyl-bicyclophosphorothionate ([35S]TBPS) binding. This
      radioligand was chosen because, like organochlorine insecticides, it binds
      directly to GABA(A) receptor/Cl- channels. [35S]TBPS binding was analyzed in
      extensively washed membranes from E17 brainstem and whole brain with the
      brainstem removed ('rest of brain') at a TBPS concentration that approximated the
      KD determined in [35S]TBPS saturation binding experiments performed on normal E17
      rat brainstem. In utero exposure to dieldrin, lindane, or bicuculline from E12
      E17 caused a significant reduction in the amount of [35S]TBPS binding in E17
      brainstem compared to vehicle-injected controls, but had no significant effect on
      'rest of brain'. These data suggest that in utero exposure to organochlorine
      insecticides that act as GABA(A) antagonists negatively regulate expression of
      GABAA receptors in fetal brainstem. If these effects persist, they could lead to
      disturbances in postnatal functions of the ascending GABAergic system, possibly
      with behavioral consequences.

PMID- 9600389
TI  - Temporospatial relationships between macroglia and microglia during in vitro
      differentiation of murine stem cells.
AB  - Embryonic stem (ES) cells of the permanent line BLC6 derived from a 129/Sv Gat
      mouse blastocyst were differentiated as spheroid aggregates (embryoid bodies,
      EBs) in the presence of retionic acid. After 2 days in suspension, EBs were
      plated on gelatine-coated glass coverslips and cultivated for 5, 9, and 16 days
      post plating (DPP) in normal medium. In this study we investigated whether the
      well-known retinoic acid-induced differentiation of ES cells into neurons
      (identified by immunostaining for neuron-specific enolase and synaptophysin) was
      accompanied by cells expressing astroglial (GFAP), oligodendroglial (O4), and
      microglial (5C6, galectin-3) markers. Whereas differentiation of neurons was
      closely related to their centrifugal migration towards the periphery of the EBs,
      the maturation of neuroglia followed a strict time-dependent manner. At 5 DPP,
      only neurons but no cells expressing glia-specific markers, were observed. At 9
      DPP, GFAP-positive and O4-positive macroglial cells appeared. At 16 DPP,
      microglial cells (5C6-positive and galectin-3-positive) occurred. The established
      dynamic of relationships between neuronal and nonneuronal cells shows that the
      model of EBs is similar to the sequence differentiation of the nervous tissue.
      Thus, enabling in vivo observation of neurons, astrocytes, oligodendrocytes, and
      microglia, the model of EBs provides a basis for further investigations on the
      relationships between neurons and neuroglia under various experimental
      conditions.

PMID- 9600390
TI  - Relation between cerebral blood flow and extracellular glucose in rat striatum
      during mild hypoxia and hyperoxia.
AB  - Rats were exposed to mild hyperoxia and hypoxia by the administration of
      oxygen/air and nitrogen/air mixtures through plastic tubing held close to their
      snouts for periods of 3 min. Changes in tissue oxygen were monitored at an
      implanted carbon paste electrode; local cerebral blood flow (rCBF) at an
      implanted platinum electrode using the hydrogen clearance technique;
      extracellular brain glucose at an implanted glucose oxidase-based biosensor and
      changes in lactate were measured using microdialysis. The nitrogen/air mixture
      led to a decrease in tissue oxygen, an increase in rCBF, a decrease in
      extracellular glucose, and an increase in lactate. The oxygen/air mixture led to
      an increase in tissue oxygen and extracellular glucose but no change in lactate
      or rCBF. The effects in unanaesthetised rats were compared with those in rats
      given 350 mg/kg chloral hydrate. The increase in lactate was greater in
      unanaesthetised than anaesthetised rats. The results show a dissociation between
      changes in rCBF and extracellular glucose and suggest that changes in oxygen
      affect utilisation rather than supply of glucose to the extracellular
      compartment.

PMID- 9600391
TI  - Relationship between dye coupling and spontaneous activity in developing ferret
      visual cortex.
AB  - Neuronal coupling by gap junctions is common during early development of the
      brain. Coupling is thought to create functional cell assemblies which may be
      involved in the functional specification of brain areas and the formation of
      synaptic circuits. In the present study we used slices from the visual cortex of
      postnatal ferrets to investigate the temporal relationship of gap junction
      coupling and formation of functional synapses. Individual neurons were filled
      with the gap-junction-permeable dye biotin ethylenediamine while spontaneous
      synaptic currents were recorded using whole-cell patch clamp recording
      techniques. We found that dye coupling increased during the first 2 postnatal
      weeks resulting at a peak around P14, after which coupling steadily decreased
      until adult levels were reached in animals older than P30. Spontaneous synaptic
      activity increased 30-fold between birth and maturity (from 10.8 +/- 2.4 to 318
      +/- 54 events/min). The sharpest rise in synaptic activity, an over 5-fold
      increase, occurred between P15 and P19, shortly after the invasion of
      thalamocortical fibers.

PMID- 9600392
TI  - Effect of sympathetic innervation on isoproterenol-induced cystatin S gene
      expression in rat submandibular glands during early development.
AB  - The rat submandibular gland is innervated by both sympathetic and parasympathetic
      branches of the autonomic nervous system which, in turn, regulate the secretory
      function of the gland. Parasympathetic innervation of rat submandibular glands is
      present at birth; in contrast, sympathetic innervation reaches the glands by
      postnatal day 5. Isoproterenol (IPR), a beta-adrenoreceptor agonist, induces
      hypertrophic and hyperplastic enlargement of rat salivary glands, and induces the
      expression of a number of genes, including cystatin S (Cys S), a member of family
      2 of the cysteine proteinase inhibitor superfamily. Cys S gene expression is
      tissue specific, cell type specific, occurs temporally during normal development
      and is not observed in adult animals unless stimulated by IPR. In addition,
      sympathectomy of adult rat submandibular glands reduced IPR-induced expression of
      the Cys S gene. This paper reports experiments analyzing the participation of the
      sympathetic branch of the autonomic nervous system in IPR-induced expression of
      the cystatin S gene during early development of the submandibular gland. The rat
      Cys S gene could be induced by IPR by day 3, and the level of Cys S mRNA remained
      constant until 8 days at which time a dramatic IPR induction of Cys S mRNA was
      observed. This statistically significant increase in Cys S mRNA at 8 days was
      diminished, but not completely suppressed, upon sympathectomy of 1-day-old
      animals. These data indicate that an intact sympathetic innervation is not a
      requisite for IPR-induced Cys S gene expression in developing submandibular
      glands; however, sympathetic innervation is required for the full IPR response of
      the Cys S gene in developing submandibular glands. The developmental experiments
      presented in this paper indicate that factor(s) coming from the sympathetic
      nervous system participate in IPR-induced expression of the Cys S gene in rat
      submandibular glands.

PMID- 9600393
TI  - Transient increase in cerebellar transcriptional activity precedes the expression
      of GABA(A) receptor alpha6 subunit mRNA during postnatal maturation.
AB  - The purpose of this study was to investigate the postnatal expression of GABA(A)
      receptor alpha6 subunit genes in the context of cerebellar differentiation. We
      examined steady-state levels of GABA(A) receptor alpha1 and alpha6 subunit mRNAs,
      polyadenylated (polyA+) mRNA and beta-actin mRNA in7-, 14-, 21-, 28-, 35-, 49-
      and 120-day-old rats. Messenger RNA expression and splicing were evaluated in
      parallel using Northern blot analysis and in situ hybridization histochemistry.
      The expression of mature GABA(A) receptor alpha6 subunit mRNA species (2.7 kb)
      was found 1 week after birth in cerebellar granule cells. Prior to stable
      expression of the mature alpha6 subunit gene, we detected large alpha6 subunit
      premessengers (3.8 and 3.5 kb) by Northern blot analysis. These premessenger
      species were detected in prenatal day (PND) 15 and neonatal rat cerebellum, when
      the mature alpha6 subunit mRNAs (2.7 kb) were not yet expressed. The maximal
      expression of mature alpha6 subunit mRNA species was observed at PND 21 when the
      peak level of cerebellar transcriptional activity was measured by polyA+ RNA
      levels. In contrast, beta-actin mRNA expression was decreased at PND 21 compared
      to birth levels. These major transcriptional events take place during a period of
      about 1 week (between PND 14 and 21), immediately following the most active phase
      of cell division in the external granule layer and migration of granule cells to
      the internal granule cell layer. Comparison between the relative abundance of
      these genes shows that differential regulation of each gene occurs during
      postnatal development. The induction of GABA(A) receptor alpha6 subunit gene
      expression is preceded by a reduction in beta-actin mRNA levels and a transient
      increase in total transcriptional activity. The expression of alpha6 subunit mRNA
      is maintained at the PND 21 level through adulthood, but the alpha1 subunit mRNA
      levels decrease drastically within the following week (from PND 21 to 28). These
      results suggest that tissue-specific expression of the GABA(A) receptor alpha6
      subunit gene is correlated with a series of developmentally regulated morphologic
      and transcriptional events.

PMID- 9600395
TI  - Towards global consensus and cooperation in health informatics and telematics
      standardisation. 1st IMIA WG16 meeting. Bermuda, 11-13 September 1997.

PMID- 9600394
TI  - Prenatal exposure to the pesticide dieldrin or the GABA(A) receptor antagonist
      bicuculline differentially alters expression of GABA(A) receptor subunit mRNAs in
      fetal rat brainstem.
AB  - We have previously shown that GABA acts as a trophic signal for monoamine neurons
      in embryonic day 14 (E14) rat brainstem cultures [Liu et al., J Neurosci 1997a;
      17:2420-2428]. The organochlorine pesticide dieldrin and the classical GABA(A)
      receptor antagonist bicuculline interfere with the trophic actions of GABA and
      alter expression of several GABA(A) receptor subunit mRNA transcripts in these
      cultures [Liu et al., J Neurosci Res 1997b;49:645-653]. In the present study, we
      investigated whether prenatal exposure to dieldrin or bicuculline from E12-17
      would alter mRNA expression of alpha1, beta3, gamma1, gamma2S and gamma2L GABA(A)
      receptor subunits in fetal (E17) rat brainstem using competitive RT-PCR to
      absolutely quantify these transcripts. The effects of dieldrin and bicuculline on
      expression of GABA(A) receptor subunit transcripts were similar across subunits.
      Dieldrin and bicuculline decreased expression of alpha1, beta3 and gamma1
      transcripts compared to vehicle-injected controls, but did not significantly
      alter expression of gamma2S and gamma2L transcripts. Taken together, these
      studies indicate that in utero exposure to organochlorine pesticides acting as
      GABA(A) receptor antagonists may alter the expression and subunit composition of
      developing GABA(A) receptors. If these changes persist, they could have long
      lasting effects on developing GABAergic neural circuitry, GABA(A) receptor
      function and GABA-mediated behaviors.

PMID- 9600396
TI  - What is done, what is needed and what is realistic to expect from medical
      informatics standards.
AB  - Medical informatic experts have made considerable progress in the development of
      standards for orders and clinical results (CEN, HL7, ASTM), EKG tracings (CEN),
      diagnostic images (DICOM), claims processing (X12 and EDIFAC) and in vocabulary
      and codes (SNOMED, Read Codes, the MED, LOINC). Considerable work still remains
      to be carried out. Abstract models of health care information have to be created,
      to cover the necessary domain, and yet be simple enough to assimilate, implement,
      and manage. This requires a high degree of abstraction. Enormous amounts to
      develop standardized vocabulary are still required to complement such a model,
      and to define the subsets that apply to given contexts.

PMID- 9600397
TI  - Standardization in health informatics in Canada.
AB  - Around the world, informatics has been cited as a key enabler of health sector
      reform. Recent reform programs in Canada, reflecting this global consensus, have
      emphasized the importance of quality information and information technology in
      meeting their goals. Standards are an important building block for achieving the
      required comprehensive and integrated health information infrastructure. This
      paper describes the current status of, and future plans for, health informatics
      and related standards in Canada.

PMID- 9600398
TI  - A new twist in US health care data standards development: adoption of electronic
      health care transactions standards for administrative simplification.
AB  - To reduce the costs of common administrative transactions, health plans, payers
      and providers encouraged the US Congress to legislate administrative
      simplification of specific electronic health data transactions. The Health
      Insurance Portability and Accountability Act (HIPAA) of 1996 created incentives
      for a public-private partnership to develop and implement standards for the
      uniformity of health care data used in electronic administrative health
      transactions and standards for the privacy and security of individually
      identifiable health information. The standards' requirements of HIPAA and how
      they have been met by the US government hold promise for accelerating the uniform
      adoption of standards developed by accredited standards developing organizations.
      The transactions designated by Congress, the process of choosing the standards in
      the Department of Health and Human Services, the principles that guided these
      choices, and the actual choices, are presented here. A successful partnership for
      administrative health data standards can pave the way for success in clinical
      health data standards and their application in computer-based patient record
      systems.

PMID- 9600399
TI  - Towards developing a national health information standards framework for South
      Africa.
AB  - An outline is given of the development of a health information standards
      framework for South Africa. The main emphasis has been in the development of data
      standards including coding schemes. Choices for diagnostic, procedure, and reason
      for encounter codes are given as well as options for personal identifiers,
      telemedicine, and pharmaceutical codes and messaging standards.

PMID- 9600400
TI  - Overcoming the barriers: national to European to G7.
AB  - An information revolution is underway which will have an impact on all sectors of
      society. It will fundamentally change national and international health systems.
      The global Internet is a key influence and will change the balance of power
      within and between healthcare professions, and between them and the general
      public. This revolution offers enormous potential benefits to global health but
      there is also potential for harm. There are a wide range of barriers to realising
      the potential benefits. They lie in areas such as the protection of personal
      information; ownership and legal accountability; data meanings: structures and
      database navigation; deficiencies in the global Internet and lack of access by
      many communities. This paper considers the nature of those barriers. In 1994, the
      Group of Seven Nations launched an initiative to stimulate a global information
      society. Theme 8 deals with healthcare and therein Sub-project 5 'Enabling
      Mechanisms', which the author leads, is seeking to identify barriers and the
      authoritative international sources of advise and good practice. It is conducting
      an international survey, the results of which should be published by the end of
      1997. This paper describes the aims of this Sub-project.

PMID- 9600401
TI  - The common principles of health informatics standardisation that require exchange
      of information between the standardisation bodies of different countries.

PMID- 9600402
TI  - The BC health information standards council.
AB  - The establishment of a British Columbia (BC) Health Information Standards Council
      is one of the strategies that is helping to develop and implement BCs vision for
      health information management. This vision is of effectively and efficiently
      managed information that enables informed decision making to achieve the results
      desired in our health system. The Council focuses on the identification of
      standards and guidelines that will enable, facilitate and promote effective
      health information sharing. This focus has resulted in approved and mandated
      informatics standards for use across the health system in the areas of data,
      applications, technology, security, confidentiality and privacy.

PMID- 9600403
TI  - How to create awareness and ensure broad dissemination of health informatics
      standards.
AB  - There is a range of organisations with responsibility for information standards
      development within Australia. These include Standards Australia, which is
      formally linked to the International Organisation for Standards (ISO), the
      National Health Information Management Group, which deals with the government
      sector and several statutory organisations such as the Australian Institute of
      Health and Welfare and the National Centre for Classification in Health. The
      different constituencies involved with each of these organisations, the scope of
      healthcare informatics and the rate of organisational and technological change in
      the industry present a significant challenge in ensuring that the standard
      setting process is highly visible, responsive and capable of demonstrating its
      value through effective implementation. Creating awareness and ensuring broad
      dissemination of healthcare informatics standards is a key component in meeting
      this challenge. This can operate at a number of levels from strategic to
      operational. At the strategic level, it requires active engagement and commitment
      of the key decision-makers, both political and professional. This may require
      directly lobbying and promoting the benefits of standardisation to those decision
      makers but can be achieved even more effectively by creating industry awareness
      and demand through carefully targeted presentations on the impact of standards to
      broader health industry forums. At the tactical level, the standards development
      medium itself can be used to engage and gain commitment from government,
      professionals, vendors and the health industry by operating as an inclusive, open
      and effective process. At the operational level, there is the opportunity for
      much more efficient use of technology to create awareness of both these processes
      and their outcomes. The establishment in Australia of a web enabled National
      Health Information Knowledge base built around ISO standards is one example of
      the type of development which will assist in the acceleration of awareness of
      standards and standardisation, which is needed to cope with the increasing
      demand.

PMID- 9600404
TI  - Standardization and security for the EMR.
AB  - The Ministry of Health and Welfare of Japan announced 'Healthcare Information
      Strategy 21' in 1994. This report shows that the Healthcare Information System is
      the key to improving the quality and efficiency of healthcare. One of the
      elements for realizing the new Healthcare Information System is the Electronic
      Medical Record (EMR). Following the publication of this report, work began with
      the aim of discovering a way to recognize the EMR as formal documentation and
      four national projects of research and development have been started. The themes
      of these projects are: 'Interoperability of EMR', 'Standardization of EMR',
      'Modeling of the Clinical Process' and 'Security for EMR'. The Japanese
      Association of the Healthcare Information Systems Industry (JAHIS) is in charge
      of 'Security for EMR'. There are many discussions in relation to the security for
      EMR. However, many of these discussions relate to information technology, while
      there are few discussions regarding definitions of security. Therefore, there are
      many different theories about security itself, which will be an obstacle to
      standardization. To design the security system for EMR, JAHIS has defined
      'Security for EMR' as the first step. The present study was conducted with
      medical informatics and security specialists. It has designed 'Requirement
      Definitions', 'Goals of Security', 'Estimation of threats to security',
      'Necessity conditions' and a 'Security Model'. This paper covers these
      definitions and our security design concept.

PMID- 9600405
TI  - Who will standardise the standardisers: an analysis of the evolution of the
      standards-making process.
AB  - For many years, there have been a number of different bodies producing standards-
      formal standards bodies, collaborative organisations and industrial consortia.
      Each process has its own advantages and disadvantages. More recently, there have
      been considerable efforts made to bring these processes together and to optimise
      the standards-making process for the benefit of standards-makers, industry and
      the end-user. This paper describes the various means by which standards are
      currently produced, examines their advantages and disadvantages and discusses how
      they are converging. It also indicates the likely results of this convergence.

PMID- 9600406
TI  - Standardization strategy from a European perspective.

PMID- 9600407
TI  - Practical development of re-usable terminologies: GALEN-IN-USE and the GALEN
      Organisation.
AB  - Medical terminology is now playing a key role in medical software. This requires
      new techniques with which many clinical users, classification experts and
      applications developers are unfamiliar. There is a conflict in that the more re
      usable techniques for terminology needed to support sharing of information among
      many different applications are more difficult to use for any one application. A
      layered approach to re-use is described which combines techniques from first
      generation systems and relatively easily understood second generation systems
      with the formal rigour of third generation systems to resolve this conflict. The
      methodology also provides a potentially rigorous approach to defining the
      relationship between terminology and structure in the electronic healthcare
      record architecture. It provides a natural migration pathway from existing
      systems to powerful re-usable multilingual terminologies.

PMID- 9600408
TI  - From a time standard for medical informatics to a controlled language for health.
AB  - CEN ENV 12381 is a European Prestandard focusing on formal representation and
      explicit reference of temporal information in healthcare informatics and
      telematics. One of its merits is not just the possibility to represent natural
      language expressions containing time-related information in a structured way, but
      also to give some mechanisms on how clinical language itself can be used to
      convey meaning unambiguously. As such, CEN ENV 12381 introduces the notion of
      'controlled language use' in the domain of healthcare. In this paper the
      principles behind controlled language design and use are explained. Through a
      detailed study of the inconsistencies and ambiguities that arise when
      interpreting Snomed procedure terms in the framework of the Galen-In-Use project,
      it is shown that most of them can be explained as a violation of sound term
      formation principles. A proposal is made to develop a controlled language for
      health and to use it in subsequent versions of coding and classification systems.
      It is expected that such an endeavour will lead to a more effective application
      of linguistic engineering in areas such as automatic knowledge acquisition,
      automatic translation, and terminology validation in the domain of healthcare
      informatics.

PMID- 9600409
TI  - Coding systems and classifications in healthcare: the link to the record.

PMID- 9600410
TI  - Exploiting the terminological approach from CEN/TC251 and GALEN to support
      semantic interoperability of healthcare record systems.
AB  - We apply the principles included in two CEN standards (ENV 12265, ENV 12264) to
      the analysis of the semantic structure of health record systems, to support their
      semantic interoperability. This result was made possible by dramatic
      methodological progress in the field of terminological systems--due to a
      worldwide evolution towards a new generation--and by the experience we acquired
      in the GALEN-IN-USE (formerly GALEN) project. The meaning behind names, content
      and context of record items and record item complexes can be considered as a
      'semantic continuum'. This continuum is made explicit, by building a suitable
      paraphrase in a controlled language. We can then apply the principles we
      previously elaborated for the second generation of terminological system.
      Methodology and tools for generating a controlled language and a second
      generation terminological system were developed and successfully used in the
      GALEN-IN-USE project and promising experiments were performed on elements of
      record structure listed in LOINC and SDM. In this way, the semantic structures of
      different record systems can be expressed by the resulting common formalism and
      thus, information units can be faithfully exchanged among different structures.

PMID- 9600411
TI  - Critical assessment of healthcare informatics standards.

PMID- 9600412
TI  - Why industry is not embracing standards.

PMID- 9600413
TI  - The Andover Working Group--accelerating the implementation of standards.
AB  - The Andover Working Group was formed with the objective to accelerate and broadly
      deliver standards-based solutions for healthcare which feature plug and play
      interoperability across the continuum of care. In this paper, organization and
      processes used by the Andover Working Group are discussed. A description of how
      multilateral message profiles, combined with object-oriented component middleware
      supporting application developments, systems integration and systems operation
      remove many of the barriers to deployment of systems of standards based
      applications is also given.

PMID- 9600414
TI  - Improving acute care through use of medical device data.
AB  - The Medical Information Bus (MIB) is a data communications standard for bedside
      patient connected medical devices. It is formally titled IEEE 1073 Standard for
      Medical Device Communications. MIB defines a complete seven layer communications
      stack for devices in acute care settings. All of the design trade-offs in writing
      the standard were taken to optimize performance in acute care settings. The key
      clinician based constraints on network performance are: (1) the network must be
      able to withstand multiple daily reconfigurations due to patient movement and
      condition changes; (2) the network must be 'plug-and-play' to allow clinicians to
      set up the network by simply plugging in a connector, taking no other actions;
      (3) the network must allow for unambiguous associations of devices with specific
      patients. A network of this type will be used by clinicians, thus giving
      complete, accurate, real time data from patient connected devices. This
      capability leads to many possible improvements in patient care and hospital cost
      reduction. The possible uses for comprehensive automatic data capture are only
      limited by imagination and creativity of clinicians adapting to the new hospital
      business paradigm.

PMID- 9600415
TI  - HL7 version 3--an object-oriented methodology for collaborative standards
      development.
AB  - In January of 1997, Health Level Seven (HL7) began developing Version 3.0 of its
      standard. The Version 3 effort represents a transformation of the way that HL7
      and its Technical Committees will develop future HL7 information interchange
      standards. This transformation involves applying object-oriented modelling to the
      development and specification of information interchange standards. This paper
      discusses the rationale that led HL7 to undertake this change and provides an
      overview of the Version 3 Message Development Framework which is HL7's new
      methodology. It also considers the features of the Version 3 methodology that can
      facilitate the development of international collaboration and consensus in health
      informatics standards.

PMID- 9600416
TI  - Aspects of implementing and harmonizing healthcare communication standards.
AB  - A variety of healthcare communication standards (HCS) have been developed during
      the last decade. They have improved the interoperability and the connectivity in
      open hospital information systems to a large extent. They have also reduced time
      and efforts during the implementation of standard interfaces. However, the
      implementation of communication standards is still far from the expected plug and
      play. The two reasons which are the main cause the current drawbacks are
      identified--the lack of a standardized terminology and the restricted flexibility
      of the currently used interchange formats. On the one hand the standardization of
      the terminology can not be solved by the standards development organizations. It
      is a general challenge for the medical informatics community. On the other hand
      the movement to a new interchange format can be initiated by standards
      development organizations. The application of SGML/XML as an interchange format
      for communication standards offers a much greater flexibility and adaptability to
      user needs than the currently used interchange formats. Concepts for a smooth
      change to a new direction are discussed.

PMID- 9600417
TI  - The CEN healthcare information systems architecture standard and the DHE
      middleware. A practical support to the integration and evolution of healthcare
      systems.

PMID- 9600418
TI  - Active X based standards for healthcare integration.
AB  - With cost pressures brought to the forefront by the growth of managed care, the
      integration of healthcare information systems is more important than ever.
      Providers of healthcare information are under increasing pressure to provide
      timely information to end users in a cost effective manner. Organizations have
      had to decide between the strong functionality that a multi-vendor 'best of
      breed' architecture provides and the strong integration provided by a single
      vendor solution. As connectivity between systems increased, these interfaces were
      migrated to work across serial and eventually, network, connections. In addition,
      the content of the information became standardized through efforts like HL7 and
      ANSI X12 and Edifact. Although content-based standards go a long way towards
      facilitating interoperability, there is also quite a bit of work required to
      connect two systems even when they both adhere to the standard. A key to
      accomplishing this goal is increasing the connectivity between disparate systems
      in the healthcare environment. Microsoft is working with healthcare organizations
      and independent software vendors to bring Microsoft's powerful enterprise object
      technology, ActiveX, to the healthcare industry. Whilst object orientation has
      been heralded as the 'next big thing' in computer applications development,
      Microsoft believe that, in fact, component software is the technology which will
      provide the greatest benefit to end users.

PMID- 9600419
TI  - Patient health record on a smart card.
AB  - A validated health questionnaire has been used for the documentation of a
      patient's history (826 items) and of the findings from physical examination (591
      items) in our clinical ward for 25 years. This computerized patient record has
      been completed in EUCLIDES code (CEN TC/251) for laboratory tests and an ATC and
      EAN code listing for the names of the drugs permanently required by the patient.
      In addition, emergency data were also included on an EEPROM chipcard with a 24 kb
      capacity. The program is written in FOX-PRO language. A group of 5000 chronically
      ill in-patients received these cards which contain their health data. For
      security reasons the contents of the smart card is only accessible by a doctor's
      PIN coded key card. The personalization of each card was carried out in our
      health center and the depersonalized alphanumeric data were collected for further
      statistical evaluation. This information served as a basis for a real need
      assessment of health care and for the calculation of its cost. Code-combined with
      an optical card, a completely paperless electronic patient record system has been
      developed containing all three information carriers in medicine: Texts, Curves
      and Pictures.

PMID- 9600420
TI  - SCP-ECG and Vital Signs Information Representation--two examples of successful
      transcontinental cooperation in medical informatics standardization.
AB  - During the past 2-3 decades, development work on Medical Devices focused on
      improving their functionality (device control, signal analysis, pattern
      recognition and classification). At present, the dominant user requirement is
      information integration. This requires interconnectivity and interoperability of
      devices and device systems. Today, due to all major manufacturers operating
      globally, this requirement can only be met if standards with global relevance are
      developed. The first standard discussed is the Standard Communications Protocol
      for Computerized Electrocardiography (SCP ECG). The rapid finalization of the
      standards document itself was possible due to some of the experts being involved
      on basic problems for greater than 10 years. Their knowledge and long standing
      cooperation contributed significantly to a fast consensus finding process as well
      as quick implementation. The second standard discussed in this paper deals with
      Vital Signs Information Representation. Before starting to write the document, an
      International inventory workshop was held to document the state of the technology
      and of user requirements. This common base of problem understanding makes
      consensus finding less difficult. Continuous cooperation between the IEEE P1073
      group and the CEN/TC251 WG5 project team also ensures early harmonization of the
      related standards. Finally, early implementation projects in Europe and the US
      allow verification and modifications based on feed-back from practical
      experience.

PMID- 9600421
TI  - Structured reporting in gastrointestinal endoscopy: integration with DICOM and
      minimal standard terminology.
AB  - The interest of the international gastrointestinal endoscopy community in
      developing standards for endoscopic reporting resulted in a standard lexicon for
      describing endoscopic findings. It became clear that in order to facilitate the
      widespread use of this lexicon, a messaging standard which could link images to
      text had to be adopted. The DICOM 3.0 Standard (digital imaging and communication
      in medicine) was extended by the introduction of the Visible Light Supplement and
      the SNOMED-DICOM microglossary. These two standards should expand the ability of
      DICOM to accommodate endoscopic images and the clinical description of these
      images.

PMID- 9600423
TI  - The minimal standard terminology for digestive endoscopy: introduction to
      structured reporting.
AB  - The wider use of computers for the management of endoscopic data and the use of
      electronic endoscopes for the production of high quality endoscopic images has
      made the standardization of terminology and images formats necessary in digestive
      endoscopy reports. The European Society for Gastrointestinal Endoscopy and the
      American Society for Gastrointestinal Endoscopy have combined their efforts to
      propose a Minimal Standard Terminology for Computerized Databases in Endoscopy.
      This terminology is based on the following principles: no term describing
      findings less frequent than 1%, of the daily practice, and no term based on
      subjective impressions. The Minimal Standard Terminology has been developed
      according to the natural process of constructing an endoscopic report in natural
      language and deals with the following: reasons for performing the examination,
      endoscopic findings, endoscopic diagnosis, additional therapeutic and diagnosis
      procedures (biopsies, etc.). It is subdivided according to the main organs
      examined with an endoscopy. Until now, the Minimal Standard Terminology was
      tested in many centers and was shown to accurately cover 95% of routine
      examinations for the upper gastrointestinal tract, colonoscopy and cholangio
      pancreatography. It is currently being tested in an a prospective way in several
      centers in Europe (with a grant from the European Commission DGXIII-C4) and in
      the USA (with grant from the AHDHF).

PMID- 9600424
TI  - Standardisation in medical image management.
AB  - A medical image without the relevant associated data is of no value. What is
      relevant depends on the use which is to be made of the image. The associated data
      may be divided into groups associated with the patient, the image data (array
      size, data type), the image itself (e.g. acquisition method), the requested
      imaging procedure to which it belongs, graphical, numerical and time information
      associated with the images, relevant results of other medical procedures, etc.
      Images, digital images and the associated data must be managed in an efficient
      manner in order to deliver appropriate patient care. In order to realise fully
      the potential of digital imaging, digital image data must be transmitted from
      acquisition units and stored in such a way as to allow appropriate access to
      health care practitioners in the imaging department, hospital and community.
      Standards exist for the formatting and transmission of image and related data
      (Digital Imaging and Communications in Medicine (DICOM). NEMA PS 3.1-PS3.12, The
      National Electrical Manufacturers Association, Rosslyn, VA, 1992, 1993, 1995;
      Health Level Seven, An Application Protocol for Electronic Data Exchange In
      Healthcare Environment, version 2.2, Health Level Seven Inc., Ann Arbor, MI,
      1994; Comite European de Normalisation, Technical Committee 251: Medical
      Informatics) although further work is required in order to improve
      interoperability. There is some overlap in current standards, thus an important
      area is the agreement on the scope of the work to be done by different bodies.
      Standards are lacking in the areas of image management and presentation.
      Strategies for the efficient use of a memory hierarchy to achieve satisfactory
      archiving and access must be developed and this depends on the existence of
      appropriate descriptive data fields. Specific issues exist regarding security of
      image data. Key areas requiring immediate work are the profiling of descriptive
      data elements according to different clinical application needs in order to
      improve interoperability and the development of strategies for evolution from
      legacy systems to modern networked systems. The best way forward is to
      consolidate and refine existing specifications.

PMID- 9600422
TI  - A European de facto standard for image folders applied to telepathology and
      teaching.
AB  - Since 1980, French pathologists at ADICAP (Association pour le Developpement de
      l'Informatique en Cytologie et en Anatomie Pathologique) have created a common
      language code allowing the use of computers for routine applications. This code
      permitted the production of an associated exhaustive image bank of approximately
      30,000 images. This task involved many specialists necessitating the definition
      of specific processes for security and simplicity of data handling. In
      particular, it has been necessary to develop image communication. To achieve that
      goal, it was necessary to define a folder, associating textual information to
      images. That was done through several industrial software providers contribution.
      Consequently, this folder, using a common packaging standard, allowed any
      pathologist access to images, codified data and clinical information. Accessing
      folders has been made easy by launching a Web server at CRIHAN under the
      supervision of ADICAP. An ADICAP software user may not only browse through the
      folder but may also import them into their own system and produce new folders.
      Today more than a hundred users in France and in foreign countries are able to
      provide diagnostic advice and also referential products useful for further
      education and quality control. The next challenge is the development of this
      preliminary de facto approach toward an internationally admitted standard suited
      for morphological image exchange.

PMID- 9600425
TI  - Standardizations of clinical laboratory examinations in Japan.
AB  - In this paper we introduce Japanese activities concerning laboratory examinations
      by illustrating three major categories. The first is the contribution of JCCLS to
      ISO/TC212 clinical laboratory testing and in vitro diagnostic test systems, with
      NCCLS and CEN TC140. The second is the establishment and promotion of JLAC
      Classification and Coding for Clinical Laboratory Tests by The Japan Society of
      Clinical Pathology. The third is a clinical data exchange format between
      healthcare facilities using MML/MERIT-9 standard, started as a Ministry research
      project.

PMID- 9600426
TI  - Negative-pressure dressings as a bolster for skin grafts.
AB  - Contoured wounds needing closure with skin grafts are often located in complex
      anatomic regions or are in unusual positions, which make conventional skin graft
      stabilization techniques cumbersome and ineffective. Often after 72 hours, a skin
      graft covered with a bolstered dressing has poor take secondary to shear
      stresses, as well as hematoma formation or serum collection, negating the
      effectiveness of the stabilizing dressing. The Food and Drug Administration has
      recently approved vacuum-assisted closure (V.A.C.), an innovative technique using
      negative pressure, for closure of chronic wounds. This reportedly leads to
      enhanced granulation tissue formation and consequently more rapid
      reepithelialization of wounds compared with conventional packing with saline
      moistened gauze. Experimental studies have demonstrated increased oxygen tension,
      decreased bacterial counts, and increased granulation formation occurring under
      negative-pressure systems. Extending the use of this concept, we have coupled
      skin grafting with negative-pressure dressings for closure of large, complex open
      wounds. Our results indicate greater than 95% graft take in all patients in this
      study. This technique is extremely efficacious, with increased graft take due to
      total immobilization of the graft, thereby limiting shear forces, elimination of
      fluid collections, bridging of the graft, and decreased bacterial contamination.
      Moreover we have noted decreased edema in rotated muscle flaps, improved contour
      conformity, and shortened hospitalizations.

PMID- 9600427
TI  - Paraspinous muscle flaps.
AB  - Coverage of midline posterior wounds presents a challenge to the reconstructive
      surgeon, especially when spinal stabilization hardware has been present and
      exposed in the wound. Most commonly those wounds that involve the mid to upper
      thoracic spine have been covered by latissimus dorsi muscle or musculocutaneous
      flaps. Lower midline wounds, especially in the thoracolumbar region, have needed
      more complex means of coverage. These have included reversed latissimus dorsi
      flaps, free flaps, extended intercostal flaps, or fasciocutaneous rotation flaps.
      We have utilized a far simpler and effective muscle flap: the paraspinous muscle
      flap. We have raised paraspinous muscle flaps bilaterally and have been able to
      cover a number of difficult wounds. The wounds were presented by 8 patients with
      exposed Harrington rods, 3 patients with cerebrospinal fluid leaks, and 1 patient
      with exposed spinous processes. The wounds in 5 of these 12 patients were in the
      upper thoracic region, where a latissimus flap was utilized as an additional
      layer of muscle coverage. The other seven patients had wounds in the lower
      midline region below the potential reach of the latissimus dorsi. In the latter
      patients the only flaps employed were paraspinous muscle flaps. We had only one
      failure in all patients, which involved a recurrent cerebrospinal fluid leak in
      which there was no decompression of the cerebrospinal fluid pressure utilized in
      the immediate postoperative period to protect the dural repair. In that instance,
      a leak recurred. This paper presents the method of flap elevation and the results
      of our series.

PMID- 9600428
TI  - Humorally mediated thrombocytosis in major lower extremity trauma.
AB  - Thrombocytosis in patients undergoing free tissue transfer for coverage of
      posttraumatic lower extremity defects may be associated with an increased
      incidence of microvascular thrombosis. Patients with isolated lower extremity
      trauma have an elevated platelet count that peaks approximately 2 weeks after
      injury. It is our theory that a humoral component of trauma sera is responsible
      for the induction of this thrombocytosis. Eight patients with isolated soft
      tissue and bony trauma were included in the study. Serum was collected at
      baseline and throughout the study period. Platelet count, leukocyte count,
      hemoglobin concentration, and hematocrit were determined. Immunoassay for human
      interleukin-3 (IL-3), IL-6, and IL-11 as well as granulocyte macrophage colony
      stimulating factor (GM-CSF) were performed by solid-phase enzyme-linked
      immunosorbent assay. Balb-C mice were then injected intraperitoneally with the
      human trauma sera from all time points. Blood was collected at baseline and
      throughout the study period for determination of platelet count, hemoglobin, and
      hematocrit. Mean initial platelet count in the 8 human subjects was 152,000 per
      cubic millimeter with an average peak to 642,000 per cubic millimeter. IL-3, IL
      11, and GM-CSF were not detectable in the serum of any patient. Elevated levels
      of IL-6 were detected in all patients in a nonspecific pattern. In the murine
      model, an early and late thrombocytosis was elicited. The early peak averaged
      78.6% over baseline whereas the late peak average 81.0% over baseline. The
      induction by human trauma sera of an early and late thrombocytosis in this mouse
      bioassay supports the theory of humoral mediators. The humoral mediators are yet
      to be determined but may include IL-6.

PMID- 9600429
TI  - Keratoacanthoma: is it a real entity?
AB  - Keratoacanthoma of the skin and well-differentiated squamous cell carcinoma are
      two cutaneous neoplasms that most often occur in sun-exposed sites of light
      skinned persons. It is often difficult to distinguish these two from each other
      either clinically or histologically. The view that these two cutaneous neoplasms
      are part of the same disease entity is not new. We reviewed 150 patients with
      these two diseases in an effort to see whether any specific criteria for
      diagnosis and treatment could be achieved. It is our hypothesis that they are not
      separate diseases but within the spectrum of the same disease. Keratoacanthoma
      may be some sort of aborted malignancy or hyperplastic premalignant lesion within
      the squamous cell carcinoma spectrum. The incidence of metastases from squamous
      cell carcinoma of the skin may be as high as 3%. We do not have the courage to
      wait 3 months to see if a potentially invasive and metastatic neoplasm is indeed
      involutional. Incision biopsy may be wrought with significant histopathological
      inconsistencies. We believe that early, complete excision is the treatment of
      choice for all skin neoplasms thought to be keratoacanthoma.

PMID- 9600430
TI  - The axillary tree as a source of musculocutaneous and fasciocutaneous flaps in a
      fixed-skin porcine model.
AB  - Our understanding of muscle, fascia, and skin flap physiology is based largely on
      data obtained from rodent, rabbit, or canine models. The presence of a well
      developed panniculus carnosus confounds the extrapolation of data from these
      animals to humans. This study attempted to define microsurgically applicable
      musculocutaneous and fasciocutaneous flaps in the pig that would be comparable to
      flaps commonly used in humans. Lead oxide was injected into each axillary artery
      of three standard white domestic swine. Gross dissection and radiographic studies
      were used to define the specific anatomic fasciocutaneous territory served by the
      branches of the circumflex scapular artery. Eight musculocutaneous flaps based on
      the thoracodorsal artery and eight fasciocutaneous flaps based on the circumflex
      scapular artery were elevated. Although all flaps survived in their entirety, the
      fasciocutaneous flaps did not, as in man, have an easily dissectable axial blood
      supply. This finding suggests that the porcine scapular fasciocutaneous flap,
      although reliable as a pedicled flap, is difficult to employ as a free tissue
      transfer.

PMID- 9600431
TI  - Improved axon diameter and myelin sheath thickness in facial nerve cable grafts
      wrapped in temporoparietal fascial flaps.
AB  - Injury to the facial nerve in the temporal bone presents a challenge to the
      recovery of nerve function, in that the fallopian canal in which it lies is
      poorly vascularized. This study was designed to determine if wrapping an
      intratemporal facial nerve defect repaired with a cable graft with a well
      vascularized temporoparietal fascial (TPF) flap would improve facial nerve
      regeneration. To evaluate this question, a defect was created in the
      intratemporal left facial nerve of 10 rabbits. All nerves were repaired using
      cable grafts. In 5 animals, the nerve graft was wrapped with temporoparietal
      fascia, whereas in the other 5 rabbits it was not. Three additional animals
      underwent exposure only. The contralateral nerve served as a control in all
      animals. Quantitative analysis of the nerve graft 12 weeks after repair revealed
      greater recovery of original fiber diameter and myelin sheath thickness in TPF
      flap-wrapped repairs. Histological evidence of improved neural regeneration and
      functional nerve recovery was also seen in the repairs where the TPF flap was
      utilized. Nerve conduction and electromyographic studies of the cable-grafted
      nerve at 6 and 12 weeks were equivocal, however.

PMID- 9600432
TI  - A nerve distraction model in the rat.
AB  - Segmental loss of a peripheral nerve has been a challenging reconstructive
      problem. Management of the nerve gap has been accomplished classically with nerve
      grafting. However, autogenous nerve grafts are not always available for bridging
      large nerve gaps, and clinical results of large nerve cable grafts have been
      disappointing. Newer techniques concentrate on nerve lengthening with different
      methods. Tissue expansion of peripheral nerves has been producing promising
      results. Since the introduction of the Ilizarov external fixator, much attention
      has turned to limb-lengthening techniques and studies investigating the results
      of nerve and soft tissues lengthened during the course of this procedure. Primary
      nerve distraction may be an alternative to nerve elongation, by expansion or
      nerve grafting to repair the peripheral nerve gap. This study describes a device
      and a model for peripheral nerve distraction in a rat. Primary nerve distraction
      will need to be subjected to vigorous studies before clinical application.

PMID- 9600433
TI  - Tamoxifen downregulates TGF-beta production in keloid fibroblasts.
AB  - Keloids occur only in humans and are characterized by fibroblast overproduction
      of collagen types I and III. Keloid fibroblasts have been shown to make elevated
      levels of transforming growth factor beta (TGF-beta), a growth factor known to
      promote extracellular matrix production and fibrosis. Thus, the pathophysiology
      underlying keloid formation may be driven by the biological activity of TGF-beta.
      Tamoxifen, a synthetic, nonsteroidal antiestrogen has been shown to inhibit
      keloid fibroblast proliferation and decrease collagen production. The purpose of
      this study was to determine if a mechanism by which tamoxifen decreases keloid
      collagen production is through a downregulation of TGF-beta. Through a luciferase
      TGF-beta bioassay we found that 4 microM of tamoxifen generated a 49% reduction
      in total TGF-beta activity and 8 microM generated an 85% reduction compared with
      controls. Thus we propose that one of the mechanisms by which tamoxifen decreases
      keloid fibroblast collagen synthesis is by decreasing TGF-beta production.

PMID- 9600434
TI  - Thrombospondin-1 and its CSVTCG-specific receptor in wound healing and cancer.
AB  - Growth factors play a crucial role in the regulation of cellular proliferation
      and matrix degradation in wound healing and cancer. We have shown that
      thrombospondin 1 (TSP-1) and its cysteine-serine-valine-threonine-cysteine
      glycine (CSVTCG)-specific receptor play a key role in cell invasion and matrix
      degradation in different carcinomas. The present study was done to determine
      whether TSP-1 and its receptor show a similar pattern of expression in wound
      healing and cancer. Expression and localization of TSP-1 and its receptor were
      determined in fetal wounds, adult burn wounds, and different human malignancies
      by immunohistochemical staining and computerized image analysis. In healing
      wounds, TSP-1 was expressed in the stroma early in the process, followed by a
      steep decline. The TSP-1 receptor localized to neovessels and highly
      proliferating cells (i.e., fibroblasts, basal cells), its levels remaining
      relatively constant. Cancer cells and tumor-associated microvessels expressed the
      TSP-1 receptor, whereas TSP-1 localized predominantly to the tumor-associated
      stroma. These data suggest a critical role for TSP-1 and its CSVTCG-specific
      receptor in wound healing and cancer.

PMID- 9600435
TI  - Polyester as a bioimplantable material.
AB  - In response to the recent controversy over silicone gel implants, alternative
      substances are being sought to offer new options in bioimplantable materials.
      Polyester is a Food and Drug Administration-approved prosthetic material utilized
      in vascular grafts for decades without significant problems in body tolerance.
      Working with textile scientists, polyester (both in its woven and fibrous forms)
      was engineered to influence differential fibrous ingrowth. Implants of medical
      grade polyester were constructed in a 3-cm2 diskette configuration. Four
      combinations of material with varying layers of weave and fiber were created to
      influence tissue ingrowth differentially. Four implants were placed in separate
      dorsal pockets beneath the panniculus carnosus of each of 12 adult female New
      Zealand White rabbits. Care was taken to sort the implant types equally among the
      four quadrants such that a similar distribution of implants existed between
      animals. Implants with intact capsules were harvested at 1, 3, and 6 months, and
      were analyzed for histology, capsular thickness, and tissue ingrowth. A phantom
      mammogram was taken through the implant material that did not obscure
      interpretation. The materials were further tested to determine fiber fill-to-wet
      implant weight ratios to determine postimplantation weight predictably. Tensile
      strength was also determined.

PMID- 9600436
TI  - Sentinel lymph node mapping in melanoma of the ear.
AB  - Primary nodal drainage basins in melanoma of the head and neck are often
      unpredictable. The ear is a notorious example of an anatomic site with ambiguous
      patterns of lymphatic drainage. Preoperative lymphoscintigraphy has recently
      emerged as one modality to assist in identifying clinically relevant nodes. We
      propose that the addition of intraoperative lymph node mapping techniques that
      utilize radioactive tracers ("intraoperative lymphoscintigraphy") can increase
      the accuracy of identifying sentinel nodes and help to determine which patients
      may benefit from a complete neck dissection. This report demonstrates the
      ambiguity in identifying drainage patterns in melanoma of the ear and offers a
      reliable method of sentinel lymph node mapping. This report also addresses
      current issues regarding treatment protocols of patients with micrometastatic
      disease in the periauricular region.

PMID- 9600437
TI  - The combined use of the TRAM and expanders/implants in breast reconstruction.
AB  - The transverse rectus abdominis musculocutaneous (TRAM) flap has replaced the
      prosthetic implant as the first choice for breast reconstruction. However, we
      have found several incidences when the volume of autogenous tissue cannot fulfill
      the requirements for symmetry, especially in those patients with limited
      abdominal tissue and large ptotic breasts. The TRAM flap can be combined with
      tissue expanders and implants to obtain symmetry in these difficult
      reconstructive situations. Here we present our experience with the use of the
      TRAM flap in conjunction with expanders and saline implants. Between June 1993
      and November 1996, 4 patients underwent immediate TRAM reconstruction in
      conjunction with saline implants or tissue expanders. In 3 patients a tissue
      expander was placed beneath the pectoralis muscle following the microanastomoses
      and prior to insetting the flap. Expansion was initiated 2 to 6 weeks
      postoperatively and continued over a period of 1 to 3 months. Permanent implants
      were placed at 3 to 4 months following the initial procedure. The final patient
      underwent a bilateral free TRAM with the placement of bilateral saline implants
      at the time of the initial reconstruction. One implant was placed beneath the
      pectoralis whereas the other was placed beneath the TRAM flap. Saline implants
      were used in all patients. The decision to use the combination of implants and
      TRAM flap was multifactorial and included position of donor scar in all patients,
      large ptotic breasts in 2 patients, request for contralateral augmentation in 2
      patients, and an absence of adequate abdominal tissue in all patients. In
      addition, large skin deficits were present in 3 patients following mastectomy
      requiring the skin coverage provided by the TRAM flap. The average age of the
      patients was 41 years. Expanders were left in place for an average of 16 weeks.
      Average final implant volume was 210 cc. The average follow-up was 24 months,
      during which time there were no episodes of flap compromise, partial flap loss,
      or fat necrosis. The TRAM flap in combination with tissue expansion and implants
      provides an additional alternative in postmastectomy reconstruction. This
      technique is particularly useful in those patients in whom the need for TRAM skin
      coverage is combined with inadequate autogenous tissue and the patient request
      for large ptotic breasts.

PMID- 9600438
TI  - Plantar verrucous carcinoma following transmetatarsal amputation and renal
      transplantation.
AB  - Verrucous carcinoma is a rare, low-grade, well-differentiated squamous cell
      carcinoma that may occur anywhere on the skin. It is slow growing, enlarges
      relentlessly, and invades locally. Most cutaneous verrucous carcinomas are found
      on the plantar surface of the foot, and share many gross and histological
      characteristics common to the ubiquitous verruca vulgaris. It is not uncommon for
      verrucous carcinoma of the sole to be mistaken for the more common verruca
      plantaris. The case of a 53-year-old white male with plantar verrucous carcinoma
      following cadaveric renal transplantation, right popliteal-tibial bypass, and a
      right transmetatarsal amputation is presented. Treatment included reamputation
      followed by reconstruction with a free radial forearm fasciocutaneous flap.
      Verrucous carcinoma is a slow-growing but relentlessly invading tumor that is
      easily misdiagnosed. The extent of early resection is often inadequate. We must
      be aware that certain persistent "warts" may represent a form of cancer that is
      treated differently from common verrucae or other squamous carcinomas.

PMID- 9600439
TI  - The superficial sural artery flap in distal lower third extremity reconstruction.
AB  - Defects in the distal third of the lower leg and ankle are difficult problems to
      solve. Many partially successful solutions have been found. Even such elegant and
      successful approaches as free muscle transfer have downsides, including operative
      time, sacrificed muscle, and a small complete failure rate. An ideal solution to
      these lower extremity problems would be a flap that replaced the lost tissue with
      like tissue, that was reliable and rapid, and that handled contamination well.
      There have been a small cohort of recent reports on the use of a reverse sural
      artery flap for reconstruction of the distal lower extremity and heel. With its
      theoretical advantages in mind, the distally based sural artery flap was used in
      2 patients with significant distal lower extremity wounds and exposed bone or
      hardware. Both flaps were successful and went on to complete healing. One of the
      flaps that had been taken quite proximal showed a very small area of flap tip
      (proximal in this reverse flap) necrosis. This flap necrosis gives some
      indication of the proximal extent of the flap.

PMID- 9600441
TI  - Pediatric peripheral neuropathy in proteus syndrome.
AB  - Proteus syndrome is a rare congenital disorder comprised of subcutaneous and
      internal hamartomas, pigmented skin nevi, skull exostoses, hemihypertrophy, and
      macrodactyly of the hands and feet. A 5-year-old girl diagnosed with Proteus
      syndrome presented with distal median compression neuropathy with the primary
      complaint of severe pain involving the left hand. Surgical exploration of the
      hand revealed a lipofibromatous hamartoma of the median nerve. The transverse
      carpal ligament was released and epineurectomy of the median nerve was performed.
      The patient remains symptom free at the 9-month follow-up. This report is the
      first description of a hamartoma directly involving a peripheral nerve in Proteus
      syndrome. Decompression of the nerve with the removal of the fibrofatty neural
      sheath resulted in the resolution of the symptoms in this patient. The surgeon
      should consider this approach as a potential first line of treatment before a
      more radical resection of the nerve is contemplated.

PMID- 9600440
TI  - Vascularized muscle flaps and reoperative approach for complicated, dehisced
      sternal wounds in children.
AB  - Vascularized muscle flaps for treatment of mediastinitis and sternal wound
      dehiscence have become standard treatment practice, but triple-muscle flap
      reconstruction is reserved for the more complex wounds. The incisional approach
      for reoperation in such patients is controversial. We report an extremely ill
      infant, born at 38 weeks gestational age, who underwent an arterial switch
      procedure for transposition of the great arteries at 12 days of age. Sternal
      wound infection, dehiscence, mediastinitis, and extensive wound necrosis
      complicated the postoperative course. The cultured organism Enterobacter is a
      relatively rare cause for median sternotomy wound infection and was associated
      with massive postoperative hemorrhage. The infant underwent multiple debridements
      and at 2 months of age had reconstructive surgery with bilateral pectoralis major
      muscle advancement flaps combined with a rectus abdominis muscle flap. Three
      months postreconstruction the infant required reoperation to correct a stenosis
      at the site of the pulmonary artery anastomosis. This surgery was carried out
      through the previous median sternotomy scar because it was the safest, most
      direct approach and would also limit additional scarring. Long-term follow-up at
      2 years of age shows a well-developed young boy with no limitations in growth and
      activity.

PMID- 9600442
TI  - Hypertrophy and asymmetry of the facial muscles: a previously unrecognized
      association.
AB  - We present 6 patients who do not satisfy the criteria for inclusion into any
      known diagnostic group, although they share similar physical findings. All had
      facial findings suggestive of either mild deformational plagiocephaly or
      craniofacial microsomia; however, hypertrophic and occasionally hyperactive
      muscles of the face appear to be the unifying and distinctive feature of the
      group. Contraction of hypertrophic postauricular muscles on the affected side
      resulted in movement and contraction of the pinna. Hypertrophy of the mentalis
      and masseter muscles was also frequently observed. Additionally, anomalous neck
      musculature was seen in 4 of the 6 patients. In 2 patients, the hypertrophy of
      certain of these muscles produced enough deformity to warrant excision. This is
      the first report of such an association in the literature. Possible explanations
      are discussed.

PMID- 9600443
TI  - Late digital replantation failure: pathophysiology and risk factors.
AB  - It is generally accepted that replanted digits surviving at least 1 week
      following surgery rarely succumb to ischemic necrosis. Presented here are 2
      patients who experienced late digital replantation failure. The first patient is
      an 8-year-old boy who had his index finger replanted at the proximal phalangeal
      level. After 16 days of viability, the replanted digit became swollen and
      subsequently necrosed. The second patient is a 35-year-old man with a history of
      smoking and intravenous drug use who underwent replantation of his avulsed thumb
      at the metacarpophalangeal joint. The replanted thumb was viable at the 2-week
      follow-up, but began to show ischemic changes at 3 weeks and eventually required
      revision amputation at the interphalangeal level. Both of these patients
      demonstrate late digital replantation failure--an unusual and poorly understood
      phenomenon. A discussion of possible risk factors and potential pathophysiology
      is presented.

PMID- 9600444
TI  - Two-portal endoscopic carpal tunnel release: an outcome analysis of 333 hands.
AB  - Outcome data were collected on 239 patients who underwent endoscopic release of
      the transverse carpal ligament. The procedure was performed on 333 hands in 239
      patients. All patients had failed to respond to nonoperative management for
      carpal tunnel syndrome and had confirmatory electrodiagnostic studies. Patients
      underwent follow-up evaluations at 21, 28, and 42 days. Numbness and paresthesias
      were relieved in 98% of the operated hands, and pain was relieved in 90% of the
      hands. A satisfactory result was achieved in 325 hands, which resulted in a 98%
      overall satisfaction rate. Eighty-eight percent of the patients required only two
      or less doses of oral analgesic during the postoperative period. Only 50 hands
      undergoing endoscopic release exhibited scar tenderness or pillar pain beyond 28
      days. Excluding workers' compensation patients, 83% of the patients returned to
      work in less than 28 days (average, 14.6 days). No operative complications were
      encountered, although 1 patient experienced postoperative reflex sympathetic
      dystrophy, which responded to conservative outpatient treatment.

PMID- 9600445
TI  - A modified method of continuous venous anastomosis in microsurgery.
AB  - The continuous suture technique for end-to-end vascular anastomosis is cautioned
      against because of the risk of vessel constriction. A modified method of
      continuous suture for end-to-end venous microanastomosis is presented in which
      vessel constriction does not occur. This technique was compared with the
      conventional interrupted suture technique in the rat femoral vein, with each rat
      serving as its own control. Forty-eight Long-Evans rats were used. The mean time
      taken to complete the anastomosis was 9.8 minutes (range, 8-14 minutes) for the
      modified continuous technique and 17.7 minutes (range, 14-24 minutes) for the
      conventional interrupted technique (p < 0.05, independent t-test). In addition,
      the veins were examined under the microscope for patency and the milk test was
      performed on each anastomosis 30 minutes postanastomosis, and 1 week and 1 month
      postoperatively. Two groups of rats were sacrificed, one at 1 week and one at 1
      month, and the two different anastomoses were compared using vessel morphometry
      in 40 rats and corrosion casts in 8 rats. All veins were patent postoperatively,
      as well as at 1 week and 1 month postoperatively. Vessel morphometry confirmed a
      similar luminal surface area in all veins examined at 1 week and 1 month. A two
      way analysis of variance of vessel morphometry indicated no significant
      interaction between the methods used and the postoperative time (p = 0.60). The
      modified continuous technique is twice as quick as the conventional interrupted
      technique for end-to-end microvenous anastomosis and does not lead to vessel
      constriction.

PMID- 9600446
TI  - Gradual cranial vault expansion for the treatment of craniofacial synostosis: a
      preliminary report.
AB  - To treat craniosynostosis, skull reshaping (such as fronto-orbital advancement)
      is widely performed. Surgical techniques have improved, however several problems
      still remain, such as postoperative relapse, late resorption, and infection. The
      main reason for this is probably (1) that the "craniotomized" bone for changing
      skull contour is used as free bone grafts and (2) that dead space between the
      reshaped bone and dura is created. We have developed a new method in which
      cranial bone is expanded gradually, together with the dura, using expansion
      devices. With this approach there is no extradural dead space postoperatively and
      the cranial bone segment remains vascularized. We have performed this procedure
      in 2 patients with Crouzon's disease and in 1 patient with sagittal synostosis.
      In the Crouzon's patients, osteotomies were performed to form a one-piece fronto
      orbital bony complex without detaching the bone from the dura, and three
      expansion devices were applied. In the patient with sagittal synostosis,
      bilateral temporoparietal osteotomies were done in the same fashion and two
      expansion devices were applied. Expansion was started on the fourth postoperative
      day at a rate of about 1 mm per day. After obtaining the proper expansion, the
      devices were removed and the bone segments were fixed with miniplates and screws.
      All patients showed good results without any complications.

PMID- 9600447
TI  - Right and left.

PMID- 9600448
TI  - Re: Computer-aided preoperative planning of tissue expansion.

PMID- 9600449
TI  - Unilaterally ruptured depressor labii inferioris muscle.

PMID- 9600450
TI  - Treatment of temporomandibular dislocation.

PMID- 9600451
TI  - Immediate debridement of burn eschar and semiocclusive dressing coverage.

PMID- 9600452
TI  - Chemical cleavage of mismatch: a new look at an established method.
AB  - Chemical cleavage of mismatch (CCM), also known as chemical mismatch cleavage
      (CMC) or the HOT (hydroxylamine/osmium tetroxide) chemical method, has been used
      for detection of sequence variability with many systems since it was first
      described. Recently, adaptation to fluorescence-based detection systems has
      fundamentally changed both the execution and analysis of CCM. This review will
      outline major advances in the methodology of CCM, from the advent of PCR through
      fluorescent analysis, and includes applications and modifications of CCM.

PMID- 9600453
TI  - Molecular basis of phenylketonuria in Venezuela: presence of two novel null
      mutations.
AB  - This report describes the mutational spectrum and linked haplotypes of the
      phenylalanine hydroxylase gene in Venezuela. In this study, we have detected
      European mutations such as IVS10nt-11, R243Q, and R408W on the same haplotype
      background (6.7, 1.8, and 2.3, respectively) as in Europe. In this sample, we
      have found two novel mutations: S349L detected in two homozygous siblings on the
      background of haplotype 6.7, and a small deletion, P314fsdelC, that results in a
      frameshift and a premature stop codon detected on the background of haplotype
      4.3. The definite demonstration that mutation S349L results in a nonfunctional
      protein was shown by expression analysis in prokaryotic and eukaryotic systems.
      This mutation results in an unstable phenylalanine hydroxylase (PAH) protein
      completely devoid of enzymatic activity well correlated with the severe form of
      the disease exhibited by the homozygous patients.

PMID- 9600454
TI  - Differential occurrence of mutations in mitochondrial DNA of human skeletal
      muscle during aging.
AB  - Seven mtDNA mutations (five base substitutions and two deletions) were studied in
      skeletal muscle samples of 18 human subjects aged 1 hr to 90 years. Quantitative
      PCR procedures were applied to determine the incidence (frequency of occurrence)
      and abundance (percentage of mutant mtDNA out of total mtDNA). The base
      substitutions, in general, showed a very early onset, three such mutations being
      detectable in the muscles of infants aged 1 hr and 5 weeks. Of two disease
      associated point mutations studied, 3243 A-->G showed significant accumulation
      with age (P < 0.05), while 8993 T-->G showed no significant age accumulation (P >
      0.1). Moreover, three arbitrarily chosen mutations (not disease-associated)
      showed no age-associated accumulation: two (7029 C-->T and 7920 A-->G) showed
      little change over the years (P > 0.1), while the other (13167 A-->G) showed a
      significant decrease (P < 0.05). both the 4,977-bp and 7,436-bp deletions showed
      a significant age-associated occurrence (P < 0.01 and P < 0.05, respectively).
      The age of onset of detectable deletions is about 20-40 years; thereafter, the
      incidence and abundance of deletions tend to increase as a function of advancing
      age. The seven specific mutations were found to occur independent of each other,
      indicating the random nature of mtDNA mutations in skeletal muscle. Moreover, the
      age-associated accumulation of multiple deletions was observed in the same set of
      muscle tissues, each extract displaying a unique set of multiple PCR products.
      Thus, mutations in mtDNA occur differentially in human skeletal muscle during
      aging.

PMID- 9600455
TI  - Germline mutations in Peruvian patients with hemophilia B: pattern of mutation in
      AmerIndians is similar to the putative endogenous germline pattern.
AB  - Exogenous (e.g., environmental) mutagens produce characteristic patterns of
      mutation. In contrast, endogenous mutation processes likely are associated with
      an invariant pattern of mutation. Analysis of factor IX gene mutations among
      large samples of hemophilia B patients from multiple, widely divergent geographic
      and ethnic populations reveals a remarkably constant mutational pattern,
      suggesting that the primary germline mutational process results from endogenous
      processes rather than environmental mutagens. To test this hypothesis further, we
      have initiated a study of hemophilia B patients from Peru because relatively
      large populations of AmerIndians can be found with low admixtures of other races.
      To determine if the factor IX (FIX) germline mutational pattern in AmerIndians
      differs from the common and putative endogenous pattern, FIX gene mutations were
      characterized in an initial sample of 10 AmerIndian Peruvian patients with
      hemophilia B. A minimum of 2.2 kb of the FIX gene was examined by PCR and direct
      sequencing of all eight exons, the splice junctions, and the promoter region. The
      pattern of germline mutation in AmerIndians was similar to the pattern of FIX
      germline mutations from larger U. S. Caucasian or Mexican Hispanic samples
      (P=0.55 and 0.63, respectively). The similar pattern in this initial sample of
      the Peru AmerIndian population provides additional support for the inference that
      the FIX germline mutational pattern results from predominantly endogenous
      processes rather than exogenous mutagens.

PMID- 9600456
TI  - Two CPT2 mutations in three Japanese patients with carnitine palmitoyltransferase
      II deficiency: functional analysis and association with polymorphic haplotypes
      and two clinical phenotypes.
AB  - Carnitine palmitoyltransferase II (CPT II) deficiency manifests as two different
      clinical phenotypes: a muscular form and a hepatic form. We have investigated
      three nonconsanguineous Japanese patients with CPT II deficiency. Molecular
      analysis revealed two missense mutations, a glutamate (174)-to-lysine
      substitution (E174K) and a phenylalanine (383)-to-tyrosine substitution (F383Y)
      in the CPT II cDNA. Transfection experiments in COS-1 cells demonstrated that the
      two mutations markedly decreased the catalytic activity of mutant CPT II. Case 1
      (hepatic form) was homozygous for the F383Y mutation, whereas case 3 (muscular
      form) was homozygous for the E174K mutation. Case 2 and her brother, who were
      compound heterozygotes for E174K and F383Y, exhibited the hepatic phenotype. We
      also identified a novel polymorphism in the CPT2 gene, a phenylalanine (352)-to
      cysteine substitution (F352C), which did not alter CPT II activity in transfected
      cells. It was present in 21 out of 100 normal alleles in the Japanese population,
      but absent in Caucasian populations. Genotyping with the F352C polymorphism and
      the two previously reported polymorphisms, V368I and M647V, allowed normal
      Japanese alleles to be classified into five haplotypes. In all three families
      with CPT II deficiency, the E174K mutation resided only on the F1V1M1 allele,
      whereas the F383Y mutation was observed on the F2V2M1 allele, suggesting a single
      origin for each mutation.

PMID- 9600457
TI  - Identification of mutations in the connexin 26 gene that cause autosomal
      recessive nonsyndromic hearing loss.
AB  - Mutations in the Cx26 gene have been shown to cause autosomal recessive
      nonsyndromic hearing loss (ARNSHL) at the DFNB1 locus on chromosome 13q12. Using
      direct sequencing, we screened the Cx26 coding region of affected and nonaffected
      members from seven ARNSHL families either linked to the DFNB1 locus or in which
      the ARNSHL phenotype cosegregated with markers from chromosome 13q12. Cx26
      mutations were found in six of the seven families and included two previously
      described mutations (W24X and W77X) and two novel Cx26 mutations: a single base
      pair deletion of nucleotide 35 resulting in a frameshift and a C-to-T
      substitution at nucleotide 370 resulting in a premature stop codon (Q124X). We
      have developed and optimized allele-specific PCR primers for each of the four
      mutations to rapidly determine carrier and noncarrier status within families. We
      also have developed a single stranded conformational polymorphism (SSCP) assay
      which covers the entire Cx26 coding region. This assay can be used to screen
      individuals with nonsyndromic hearing loss for mutations in the CX26 gene.

PMID- 9600458
TI  - Three novel type I collagen mutations in osteogenesis imperfecta type IV probands
      are associated with discrepancies between electrophoretic migration of osteoblast
      and fibroblast collagen.
AB  - In three cases of type IV osteogenesis imperfecta (OI), we identified unique
      point mutations in type I collagen alpha1(I) cDNA. In two cases, the appearance
      of dimers indicated the presence of cysteine substitutions in the alpha1(I)
      protein chain. Cyanogen bromide digestion localized these cross-links to CB8 and
      3, respectively. In the third case, the overmodification pattern of the CNBr
      peptides was compatible with a substitution in the aa 123-402 region of either
      type I collagen chain. We identified a unique point mutation in each proband,
      which resulted in substitutions for glycine residues in a 300-aa region of the
      alpha1(I) helix, specifically, Gly to Ala at codon 220 (GGT-->GCT), Gly to Cys at
      codon 349 (GGT-->TGT) and Gly to Cys at codon 523 (GGT-->TGT). We compared each
      proband's fibroblast and osteoblast collagen directly, as well as with fibroblast
      and osteoblast controls. For all cases, the OI osteoblast collagen was more
      electrophoretically delayed than OI fibroblast collagen. In the patient with
      G349C, OI fibroblast and osteoblast collagen synthesized in the presence of
      alpha,alpha'-dipyridyl co-migrated on gels, demonstrating that the
      electrophoretic discrepancy resulted from differences in post-translational
      modification. Melting temperature curves for stability of the collagen helix
      yielded an identical Tm for control fibroblast and osteoblast collagen (41.2
      degrees C). By contrast, for collagen with the gly349-->cys substitution, the Tm
      of the fibroblast collagen was 1 degree C lower than the Tm of the osteoblast
      collagen. These data indicate that the metabolism of mutant collagen might be
      cell-specific and has significant implications for understanding the
      phenotype/genotype correlations and the pathophysiology of OI.

PMID- 9600459
TI  - Rapid, efficient method for multiplex amplification from filter paper.
AB  - Guthrie cards derived from the New York State Newborn Screening Program were
      utilized to develop a rapid, economical method for amplifying multiple genes to
      detect mutations that impact public health. These specimens are untraceable to
      the donor because identifiers are removed and discarded; therefore, these pilot
      studies were carried out anonymously. The sample preparation requires minimal
      manipulation, is amenable to automation, and is useful in laboratories which
      routinely process large numbers of samples, such as those in typical newborn
      screening laboratories. Multiple gene fragments may be amplified from a 1 mm
      punch which contains less than 1 microl of whole blood. The blood spots used in
      these studies contain sufficient material for up to 25 amplification reactions
      which multiplex at least four different gene fragments each. Since sufficient
      material remains on the card after the routine testing is complete, this simple
      assay can greatly expand the efficacy of current newborn screening programs by
      permitting DNA diagnosis of some disorders when indicated, particularly those in
      which genotype-phenotype correlations are useful. In addition to newborn
      screening specimens, this method is also applicable to whole blood from adults
      after phlebotomy and from lymphoblastoid cell lines. Use of filter paper for DNA
      analysis is particularly useful for shipped specimens or for population studies
      whose subjects are refractory to phlebotomy.

PMID- 9600460
TI  - A piece of my mind. Regaining compassion.

PMID- 9600461
TI  - Volunteers in typhoid infection study will aid future vaccine development.

PMID- 9600462
TI  - Bioethics group considers transnational research.

PMID- 9600463
TI  - Dermatologists call for massive cover-up.

PMID- 9600464
TI  - Diet may affect skin cancer prevention.

PMID- 9600465
TI  - From the Centers for Disease Control and Prevention. Use of folic acid-containing
      supplements among women of childbearing age--United States, 1997.

PMID- 9600466
TI  - From the Centers for Disease Control and Prevention. Suicide among black youths-
      United States, 1980-1995.

PMID- 9600467
TI  - New developments in family medicine.

PMID- 9600468
TI  - Detection of early prostate cancer: serendipitous or systematic?

PMID- 9600469
TI  - Detection of early prostate cancer: serendipitous or systematic?

PMID- 9600470
TI  - Detection of early prostate cancer: serendipitous or systematic?

PMID- 9600471
TI  - Detection of early prostate cancer: serendipitous or systematic?

PMID- 9600472
TI  - The positive aspect of tragedy: a matter of perspective.

PMID- 9600473
TI  - Hypoglycemia from glipizide and glyburide.

PMID- 9600474
TI  - Hypoglycemia from glipizide and glyburide.

PMID- 9600478
TI  - Effects of raloxifene on serum lipids and coagulation factors in healthy
      postmenopausal women.
AB  - CONTEXT: Raloxifene is a selective estrogen receptor modulator that has estrogen
      agonistic effects on bone and estrogen-antagonistic effects on breast and uterus.
      OBJECTIVE: To identify the effects of raloxifene on markers of cardiovascular
      risk in postmenopausal women, and to compare them with those induced by hormone
      replacement therapy (HRT). DESIGN: Double-blind, randomized, parallel trial.
      SETTING: Eight sites in the United States. PARTICIPANTS: 390 healthy
      postmenopausal women recruited by advertisement. INTERVENTION: Participants were
      randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120
      mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone
      acetate, 2.5 mg/d); or placebo. MAIN OUTCOME MEASURES: Change and percent change
      from baseline of lipid levels and coagulation parameters after 3 months and 6
      months of treatment. RESULTS: At the last visit completed, compared with placebo,
      both dosages of raloxifene significantly lowered low-density lipoprotein
      cholesterol (LDL-C) by 12% (P < .001), similar to the 14% reduction with HRT (P <
      .001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to
      8% (P < .001), less than the 19% decrease with HRT (P<.001). Raloxifene increased
      high-density lipoprotein-2 cholesterol (HDL2-C) by 15% to 17% (P < .05), less
      than the 33% increase with HRT (P < .001). Raloxifene did not significantly
      change high-density lipoprotein cholesterol (HDL-C), triglycerides, or
      plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and
      triglycerides by 20%, and decreased PAI-1 by 29% (for all, P < .001). Raloxifene
      significantly lowered fibrinogen by 12% to 14% (P < .001), unlike HRT, which had
      no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1
      and 2. CONCLUSIONS: Raloxifene favorably alters biochemical markers of
      cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by
      increasing HDL2-C without raising triglycerides. In contrast to HRT, raloxifene
      had no effect on HDL-C and PAI-1, and a lesser effect on HDL2-C and
      lipoprotein(a). Further clinical trials are necessary to determine whether these
      favorable biochemical effects are associated with protection against
      cardiovascular disease.

PMID- 9600479
TI  - Time to clinical stability in patients hospitalized with community-acquired
      pneumonia: implications for practice guidelines.
AB  - CONTEXT: Many groups have developed guidelines to shorten hospital length of stay
      in pneumonia in order to decrease costs, but the length of time until a patient
      hospitalized with pneumonia becomes clinically stable has not been established.
      OBJECTIVE: To describe the time to resolution of abnormalities in vital signs,
      ability to eat, and mental status in patients with community-acquired pneumonia
      and assess clinical outcomes after achieving stability. DESIGN: Prospective,
      multicenter, observational cohort study. SETTING: Three university and 1
      community teaching hospital in Boston, Mass, Pittsburgh, Pa, and Halifax, Nova
      Scotia. PATIENTS: Six hundred eighty-six adults hospitalized with community
      acquired pneumonia. MAIN OUTCOME MEASURES: Time to resolution of vital signs,
      ability to eat, mental status, hospital length of stay, and admission to an
      intensive care, coronary care, or telemetry unit. RESULTS: The median time to
      stability was 2 days for heart rate (< or =100 beats/min) and systolic blood
      pressure (> or =90 mm Hg), and 3 days for respiratory rate (< or =24
      breaths/min), oxygen saturation (> or =90%), and temperature (< or =37.2 degrees
      C [99 degrees F]). The median time to overall clinical stability was 3 days for
      the most lenient definition of stability and 7 days for the most conservative
      definition. Patients with more severe cases of pneumonia at presentation took
      longer to reach stability. Once stability was achieved, clinical deterioration
      requiring intensive care, coronary care, or telemetry monitoring occurred in 1%
      of cases or fewer. Between 65% to 86% of patients stayed in the hospital more
      than 1 day after reaching stability, and fewer than 29% to 46% were converted to
      oral antibiotics within 1 day of stability, depending on the definition of
      stability. CONCLUSIONS: Our estimates of time to stability in pneumonia and
      explicit criteria for defining stability can provide an evidence-based estimate
      of optimal length of stay, and outline a clinically sensible approach to
      improving the efficiency of inpatient management.

PMID- 9600480
TI  - Persistence of use of lipid-lowering medications: a cross-national study.
AB  - CONTEXT: Although clinical trials have demonstrated the benefits of lipid
      lowering therapy, little is known about how these drugs are prescribed or used in
      the general population. OBJECTIVE: To estimate predictors of persistence with
      therapy for lipid-lowering drug regimens in typical populations of patients in
      the United States and Canada. DESIGN: A cohort study defining all prescriptions
      filled for lipid-lowering drugs during 1 year, as well as patients' demographic
      and clinical characteristics. SETTING: New Jersey's Medicaid and Pharmacy
      Assistance for the Aged and Disabled programs and Quebec's provincial medical
      care program. PATIENTS: All continuously enrolled patients older than 65 years
      who filled 1 or more prescriptions for lipid-lowering drugs (N = 5611 in the US
      programs, and N = 1676 drawn from a 10% sample in Quebec). MAIN OUTCOME MEASURES:
      Proportion of days during the study year for which patients had filled
      prescriptions for lipid-lowering drugs; predictors of good vs poor persistence
      with therapy. RESULTS: In both populations, patients failed to fill prescriptions
      for lipid-lowering drugs for about 40% of the study year. Persistence rates with
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were significantly
      higher than those seen with cholestyramine (64.3% vs 36.6% of days with drug
      available, respectively). Patients with hypertension, diabetes, or coronary
      artery disease had significantly higher rates of persistence with lipid-lowering
      regimens. In New Jersey, multivariable analysis indicated that the poorest
      patients (those enrolled in Medicaid) had lower rates of drug use than less
      indigent patients (those enrolled in Pharmacy Assistance for the Aged and
      Disabled) after adjusting for possible confounders, despite virtually complete
      drug coverage in both programs. When rates of use were measured in the US
      population for the 5 years following the study year, only 52% of surviving
      patients who were initially prescribed lipid-lowering drugs were still filling
      prescriptions for this drug class. CONCLUSION: In all populations studied,
      patients who were prescribed lipid-lowering drug regimens remained without filled
      prescriptions for over a third of the study year on average. Rates of persistence
      varied substantially with choice of agent prescribed, comorbidity, and
      socioeconomic status, despite universal coverage of prescription drug costs.
      After 5 years, about half of the surviving original cohort in the United States
      had stopped using lipid-lowering therapy altogether.

PMID- 9600481
TI  - Medical care delivery at the 1996 Olympic Games. Centers for Disease Control and
      Prevention Olympics Surveillance Unit.
AB  - CONTEXT: Mass gatherings like the 1996 Olympic Games require medical services for
      large populations assembled under unusual circumstances. OBJECTIVE: To examine
      delivery of medical services and to provide data for planning future events.
      DESIGN: Observational cohort study, with review of medical records at Olympics
      medical facilities. SETTING: One large multipurpose clinic and 128 medical aid
      stations operating at Olympics-sponsored sites in the vicinity of Atlanta, Ga.
      PARTICIPANTS: A total of 10715 patients, including 1804 athletes, 890 officials,
      480 Olympic dignitaries, 3280 volunteers, 3482 spectators, and 779 others who
      received medical care from a physician at an Olympic medical station. MAIN
      OUTCOME MEASURES: Number of injuries and cases of heat-related illness among
      participant categories, medical use rates among participants with official Games
      credentials, and use rates per 10000 persons attending athletic competitions.
      RESULTS: Injuries, accounting for 35% of all medical visits, were more common
      among athletes (51.9% of their visits, P < .001) than among other groups.
      Injuries accounted for 31.4% of all other groups combined. Spectators and
      volunteers accounted for most (88.9%, P < .001) of the 1059 visits for heat
      related illness. The rates for number of medical encounters treated by a
      physician were highest for athletes (16.2 per 100 persons, P < .001) and lowest
      for volunteers (2.0 per 100). Overall physician treatment rate was 4.2 per 10000
      in attendance (range, 1.6-30.1 per 10000). A total of 432 patients were
      transferred to hospitals. CONCLUSIONS: Organizers used these data during the
      Games to monitor the health of participants and to redirect medical and other
      resources to areas of increased need. These data should be useful for planning
      medical services for future mass gatherings.

PMID- 9600482
TI  - Public health response for the 1996 Olympic Games.
AB  - Extensive planning and preparation by public health agencies were required for
      the provision of public health services during the 1996 Centennial Olympic Games,
      which brought together more than 10000 athletes from 197 countries and more than
      2 million visitors. Public health activities included the development and use of
      an augmented surveillance system to monitor health conditions and detect disease
      outbreaks; creation and implementation of 6 environmental health regulations;
      establishment of a central Public Health Command Center and response teams to
      coordinate response to public health emergencies; planning for potential mass
      casualties and the provision of emergency medical services; implementation of
      strategies for the prevention of heat-related illness; and distribution of health
      promotion and disease prevention information. Public health agencies should take
      the lead in organizing and implementing a system for preventing and managing
      public health issues at future large-scale public events such as the Olympics.

PMID- 9600483
TI  - Influence of a child's sex on medulloblastoma outcome.
AB  - CONTEXT: Aggressive treatment of medulloblastoma, the most common pediatric brain
      tumor, has not improved survival. Identifying better prognostic indicators may
      warrant less morbid therapy. OBJECTIVE: To investigate the role of sex on outcome
      of medulloblastoma. DESIGN: Retrospective study of significant factors for
      survival with a median follow-up of 82 months. SETTING: University medical
      center. PATIENTS: A total of 109 consecutive, pediatric patients treated for
      primary medulloblastoma from 1970 to 1995 with surgery and postoperative
      radiotherapy and, after 1979, chemotherapy. MAIN OUTCOME MEASURES: Factors
      independently associated with survival. RESULTS: The final multivariate model
      predicting improved survival included sex (hazard ratio, 0.52; 95% confidence
      interval [CI], 0.29-0.92; P=.03; favoring female), metastases at presentation
      (hazard ratio, 2.01; 95% CI, 1.14-3.52; P=.02), and extent of surgical resection
      (hazard ratio, 0.60; 95% CI, 0.34-1.04; P=.07; favoring greater resection). The
      overall, 5-year freedom from progression was 40% and survival was 49%.
      Radiotherapy dose (P=.72), and chemotherapy (P=.90) did not significantly affect
      a disease outcome. CONCLUSIONS: The sex of the child was an important predictor
      for survival of medulloblastoma; girls had a much better outcome. The difference
      in survival between sexes should be evaluated in prospective, clinical trials.

PMID- 9600484
TI  - Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with
      coronary heart disease: meta-analyses of prospective studies.
AB  - CONTEXT: A large number of epidemiologic studies have reported on associations
      between various "inflammatory" factors and coronary heart disease (CHD).
      OBJECTIVE: To assess the associations of blood levels of fibrinogen, C-reactive
      protein (CRP), and albumin and leukocyte count with the subsequent risk of CHD.
      DATA SOURCES: Meta-analyses of any long-term prospective studies of CHD published
      before 1998 on any of these 4 factors. Studies were identified by MEDLINE
      searches, scanning of relevant reference lists, hand searching of cardiology,
      epidemiology, and other relevant journals, and discussions with authors of
      relevant reports. STUDY SELECTION: All relevant studies identified were included.
      DATA EXTRACTION: The following information was abstracted from published reports
      (supplemented, in several cases, by the authors): size and type of cohort, mean
      age, mean duration of follow-up, assay methods, degree of adjustment for
      confounders, and relationship of CHD risk to the baseline assay results. DATA
      SYNTHESIS: For fibrinogen, with 4018 CHD cases in 18 studies, comparison of
      individuals in the top third with those in the bottom third of the baseline
      measurements yielded a combined risk ratio of 1.8 (95% confidence interval [CI],
      1.6-2.0) associated with a difference in long-term usual mean fibrinogen levels
      of 2.9 pmol/L (0.1 g/dL) between the top and bottom thirds (10.3 vs 7.4 pmol/L
      [0.35 vs 0.25 g/dL]). For CRP, with 1053 CHD cases in 7 studies, the combined
      risk ratio of 1.7 (95% CI, 1.4-2.1) was associated with a difference of 1.4 mg/L
      (2.4 vs 1.0 mg/L). For albumin, with 3770 CHD cases in 8 studies, the combined
      risk ratio of 1.5 (95% CI, 1.3-1.7) was associated with a difference of 4 g/L (38
      vs 42 g/L, ie, an inverse association). For leukocyte count, with 5337 CHD cases
      in the 7 largest studies, the combined risk ratio of 1.4 (95% CI, 1.3-1.5) was
      associated with a difference of 2.8 x 10(9)/L (8.4 vs 5.6 x 10(9)/L). Each of
      these overall results was highly significant (P<.0001). CONCLUSIONS: The
      published results from these prospective studies are remarkably consistent for
      each factor, indicating moderate but highly statistically significant
      associations with CHD. Hence, even though mechanisms that might account for these
      associations are not clear, further study of the relevance of these factors to
      the causation of CHD is warranted.

PMID- 9600485
TI  - Of designer drugs, magic bullets, and gold standards.

PMID- 9600486
TI  - Health care at mass gatherings.

PMID- 9600487
TI  - Beyond CONSORT: need for improved reporting standards for clinical trials.
      Consolidated Standards of Reporting Trials.

PMID- 9600488
TI  - CONSORT: an evolving tool to help improve the quality of reports of randomized
      controlled trials. Consolidated Standards of Reporting Trials.

PMID- 9600489
TI  - Effect of opportunistic illness on risk of death in HIV disease: abstract and
      commentary.

PMID- 9600490
TI  - The discontinuation of Hymenoptera venom immunotherapy.

PMID- 9600491
TI  - Correlation between alcohol-induced asthma and acetaldehyde dehydrogenase-2
      genotype.
AB  - BACKGROUND: Alcohol-induced asthma, a phenomenon characteristic of Asians, is due
      to differences in alcohol metabolism, particularly acetaldehyde metabolism. We
      investigated the effect of polymorphism in acetylaldehyde dehydrogenase 2 (ALDH2)
      gene on the response to alcohol challenge testing in a group of Japanese
      asthmatic subjects and normal subjects. METHODS: Subjects were 32 asthmatic
      subjects and 30 healthy individuals. We measured the change in FEV1 after
      ingestion of 30 gm of ethanol. Blood ethanol, acetylaldehyde, and histamine
      concentrations were determined. ALDH2 gene type was established by polymerase
      chain reaction. RESULTS: Ethanol provocation test results were positive in 15
      (47% responders) asthmatic subjects. The blood ethanol concentration was similar
      in responders and nonresponders. The fall in FEV1 was associated with a rise in
      blood acetaldehyde and histamine concentrations. The response to oral ethanol
      challenge was positive in three (19%) of 16 patients with normal homozygote ALDH2
      genotype, 10 (71%) of 14 patients with type mutant heterozygote, and two (100%)
      of two patients with type mutant homozygote ALDH2 genotype. CONCLUSIONS: Alcohol
      induced asthma is probably caused by increased blood acetaldehyde concentration
      resulting from abnormalities of ALDH2 enzyme activity based on ALDH2 genotype
      differences.

PMID- 9600492
TI  - Nasal provocation test with lysine-aspirin for diagnosis of aspirin-sensitive
      asthma.
AB  - Nasal provocation tests (NPTs) with lysine-aspirin (L-ASA) have been recently
      introduced for assessment of aspirin-induced asthma (AIA). They differ in dose
      and means of aspirin instillation, duration of observation period, and criteria
      for positivity. Thus far they have not become a routine part of clinical
      diagnosis. Fifty-one patients with AIA, confirmed by oral challenge test, were
      recruited to undergo diagnostic NPTs with L-ASA. In 10 of these patients (19.6%),
      NPTs could not be performed because of total obstruction of at least one nostril
      or marked fluctuations in nasal flows, leaving 41 patients with AIA for the
      study. Control groups consisted of 13 aspirin-tolerant asthmatic patients and 10
      healthy subjects. L-ASA at a total dose of 16 mg of acetylsalicylic acid applied
      bilaterally into the inferior nasal conchae caused significant fall in
      inspiratory nasal flow in at least one nostril (>40%), which was measured by
      anterior rhinomanometry, and clinical symptoms of watery discharge and nasal
      blockage in 35 of 41 patients with AIA, one of 10 healthy subjects, and none of
      13 aspirin-tolerant asthmatic patients. No relationship was found between the
      baseline nasal flow values and the intensity of response to L-ASA. No systemic
      reactions, including bronchospasm, were noticed, even in patients whose initial
      FEV1 was lower than 70% of predicted value. This test is highly specific (95.7%)
      and sensitive (86.7%), but negative results do not exclude possible intolerance
      to aspirin (predictive value of a negative result 78.6%). In conclusion, the NPT
      described is a simple, safe, and quick test for diagnosis of AIA. It can be used
      in patients with unstable asthma. It may be a method of choice to confirm
      hypersensitivity to aspirin manifested only by symptoms from the upper
      respiratory tract. Patients suspected of aspirin intolerance who have negative
      NPT results should undergo bronchial or oral challenge tests with aspirin.

PMID- 9600493
TI  - The prevalence of and risk factors for atopy in early childhood: a whole
      population birth cohort study.
AB  - OBJECTIVES: A birth cohort was followed-up to age 4 years to record the
      development of allergic disorders and to study the influence of genetic and
      environmental factors. METHODS: Information on family history and environmental
      factors was obtained at birth, and serum cord IgE was measured. At age 4 years,
      1218 children were reviewed. RESULTS: By age 4 years, 27% of the children had
      symptoms of allergic disease. Period prevalence of asthma increased from 8.7% in
      infancy to 14.9% at 4 years. Family history of atopy was the single most
      important risk factor for atopy in children. Sibling atopy was a stronger
      predictor of clinical disease than maternal or paternal atopy, whereas paternal
      atopy, male sex, and high cord IgE were significant for the development of
      allergen sensitization. Children of asthmatic mothers were three times more
      likely to have asthma (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.6
      5.8) and rhinitis (OR: 2.9, CI: 1.1-7.4). Formula feeding before 3 months of age
      predisposed to asthma at age 4 years (OR: 1.8, CI: 1.2-2.6). The effect of
      maternal smoking on childhood wheeze seen at 1 and 2 years was lost by age 4,
      except for a subgroup with negative skin test responses (nonatopic asthma). Less
      than half (46%) of the infantile wheezers were still wheezing at 4 years of age.
      CONCLUSION: Family history of atopy remains the most important risk factor for
      atopy in children, but other markers can be identified with a potential for
      intervention at an early age.

PMID- 9600494
TI  - Difficult-to-control asthma: clinical characteristics of steroid-insensitive
      asthma.
AB  - BACKGROUND: Although widely used, little is known regarding the patterns of
      response that subjects with severe asthma exhibit to oral glucocorticoid (GC)
      therapy. METHODS: We retrospectively reviewed the charts of 164 consecutive
      adolescents admitted to the National Jewish Medical and Research Center for
      difficult-to-control asthma. Data collected included medical history, pulmonary
      function measures by plethysmography, methacholine challenge results, AM cortisol
      levels, serum IgE, total eosinophil counts (TEC), serum eosinophil cationic
      protein (ECP), soluble IL-2 receptor (sIL-2R), and spirometry. RESULTS: Eighty
      seven patients (53%) required a GC burst during the hospitalization secondary to
      poor asthma control. Those requiring a GC burst had a significantly longer
      history of asthma, a greater degree of bronchial hyperresponsiveness, and lower
      pulmonary function. Twenty-one patients (24%) failed to respond with a greater
      than 15% improvement in their AM prebronchodilator FEV1 after the GC burst and
      were termed steroid insensitive (SI). Although those with SI asthma had a similar
      duration of asthma, they required oral GC therapy at a younger age, required a
      larger maintenance oral GC dose on admission, and were more likely to be African
      American, compared with those with steroid-sensitive asthma. Furthermore, two
      distinct spirometry patterns were noted among the SI asthmatic subjects:
      "chaotic" and "nonchaotic." Patients with the chaotic pattern were characterized
      by a significant degree of variability (greater than 30%) in daily pulmonary
      function, whereas those with nonchaotic, SI asthma were characterized by less
      than 15% variability in daily lung function. Those with nonchaotic SI were
      diagnosed with asthma and treated with oral GCs at a later age. CONCLUSIONS: This
      retrospective study suggests that SI asthma is quite common (25%) among
      adolescents with severe asthma evaluated at a national referral center. In
      addition, two distinct patterns of SI asthma have been identified that may
      constitute different pathophysiologic processes. Finally, the overrepresentation
      of African-Americans in the SI group supports the need for further epidemiologic
      studies investigating the prevalence of SI asthma and the impact early asthma
      intervention may have on this severe form of asthma.

PMID- 9600495
TI  - Treatment with hypertonic saline versus normal saline nasal wash of pediatric
      chronic sinusitis.
AB  - BACKGROUND: Chronic sinusitis (CS) is a common disease in children, especially
      those with allergies, that is caused by impaired drainage from the sinuses.
      Hypertonic NaCl solution has been shown to increase mucociliary clearance and
      ciliary beat frequency. OBJECTIVE: We performed a randomized double blind study
      to compare the effect of nasal wash with hypertonic saline (HS) (3.5%) versus
      normal saline (NS) (0.9%) on CS. METHODS: Thirty patients with CS aged 3 to 16
      years were studied. They were randomly divided into two treatment groups matched
      by age and severity of the disease. Each individual was treated with either HS or
      NS for 4 weeks. All patients were evaluated by two clinical scores (cough and
      nasal secretions/postnasal drip [PND]) and by a radiology score at the beginning
      of the study and after 4 weeks. RESULTS: The HS group improved significantly in
      all scores (average +/- SD): cough score, from 3.6 +/- 0.51 to 1.6 +/- 0.74;
      nasal secretion/PND score, from 2.86 +/- 0.35 to 1.6 +/- 0.74; and radiology
      score, from 8.06 +/- 1.28 to 2.66 +/- 1.04. The NS treatment group showed
      significant improvement only in the PND score (from 2.66 +/- 0.49 to 1.53 +/-
      0.83) but no significant change in both the cough score (from 3.53 +/- 0.52 to
      3.33 +/- 0.49) and the radiology score (from 8.13 +/- 1.25 to 7.86 +/- 0.91).
      Clinical observation 1 month after the end of the study showed no change compared
      with the end of the study in both groups. CONCLUSION: HS nasal wash is an
      efficient treatment of CS.

PMID- 9600496
TI  - Long-term protection after stopping venom immunotherapy: results of re-stings in
      200 patients.
AB  - BACKGROUND: Venom immunotherapy (VIT) protects most patients allergic to
      Hymenoptera stings while booster injections are continued. Few data on long-term
      protection after discontinuation of treatment are available. OBJECTIVE: We sought
      to investigate protection from re-stings over a prolonged period after stopping
      VIT. METHODS: Re-sting data were obtained from 200 of 322 patients in whom VIT
      had been stopped between 1988 and 1992 after a duration of at least 3 years. The
      25 (12.5%) patients who again developed systemic allergic reactions were compared
      with 50 matched patients without re-sting reactions. Clinical data and diagnostic
      parameters (i.e., skin sensitivity and specific IgE and IgG) were studied.
      RESULTS: Of the 25 patients who had re-sting reactions, 19 had been treated with
      bee venom (relapse rate, 15.8%), and six had been treated with Vespula venom
      (relapse rate, 7.5%). About half of the re-sting reactions occurred on the first
      resting after stopping VIT. Most of these reactions were mild, whereas the
      majority of reactions occurring after repeated re-stings were severe. When re
      sting reactions were related to the total re-stings per year, an accumulation of
      sting reactions was observed in years 3 to 5 after stopping VIT. Patients with re
      sting reactions had been receiving VIT for a significantly shorter duration
      (43.35 months) than those with continued protection (54.65 months) (p < 0.01). Of
      the diagnostic parameters, only a negative intracutaneous skin test at 10(-3)
      gm/L predicted long-term protection reliably. CONCLUSION: Venom immunotherapy of
      3 to 5 years duration induces long-term protection in most patients. In rare
      occasions severe re-sting reactions may, however, occur, especially after
      repeated re-stings.

PMID- 9600497
TI  - Eosinophilia and gastrointestinal symptoms after ingestion of shiitake mushrooms.
AB  - BACKGROUND: Shiitake mushrooms are a dietary staple in Asia and are increasingly
      popular worldwide. A cholesterol-lowering study with shiitake showed that 17 of
      49 participants withdrew because of rash or abdominal discomfort, and two had
      marked eosinophilia. One of these latter participants was subsequently challenged
      for 14 days with shiitake powder and again had eosinophilia. OBJECTIVE: We
      investigated whether ingestion of shiitake mushroom powder induces eosinophilia
      or symptoms. METHODS: We studied 10 normal persons. Each participant ingested 4
      gm shiitake powder (open label) daily for 10 weeks (trial 1), and the protocol
      was repeated in these same subjects after 3 to 6 months (trial 2). Blood counts
      and serum samples were obtained biweekly (trial 1) or weekly along with stool
      specimens (trial 2). Eosinophil major basic protein and IL-5, IgE, and IgG
      antishiitake antibodies were measured in sera. Eosinophil-derived neurotoxin was
      measured in stool extracts. We defined responders as subjects having peak
      eosinophil counts four or more times their average baseline counts. RESULTS: Each
      trial had four responders, and trial 2 had one new and three repeat responders.
      Eosinophilia ranged from 400 to 3900/mm3. Responders had increased blood
      eosinophils, serum major basic protein, stool eosinophil-derived neurotoxin, and
      factors that enhanced eosinophil viability. Antishiitake IgE was not detected,
      and antishiitake IgG increased in two responders. Gastrointestinal symptoms
      coincided with eosinophilia in two subjects. Symptoms and eosinophilia resolved
      after discontinuing shiitake ingestion. CONCLUSIONS: Daily ingestion of shiitake
      mushroom powder in five of 10 healthy persons provoked blood eosinophilia,
      increased eosinophil granule proteins in serum and stool, and increased
      gastrointestinal symptoms. Shiitake ingestion suggests a model to study the
      eosinophil's role in the blood and gastrointestinal tract. Finally, our report
      raises concerns of possible adverse systemic reactions to this increasingly
      popular food.

PMID- 9600498
TI  - Prevalence and risk factors of latex sensitization in an unselected pediatric
      population.
AB  - BACKGROUND: The prevalence of latex sensitization has been investigated in
      population groups considered at high risk, but it has not been systematically
      surveyed among the general population. OBJECTIVE: We sought to determine the
      prevalence of and the risk factors associated with latex sensitization in a
      general pediatric population. METHODS: We investigated 1175 children (mean age +/
      SD, 105 +/- 17.5 months) in 11 elementary schools in Tuscany (Italy). All
      parents answered a questionnaire, and children underwent skin prick tests (SPTs)
      with latex, six aeroallergens (Dermatophagoides pteronyssinus, D. farinae, cat,
      grass pollen, Alternaria tenuis, and Parietaria judaica), three food allergens
      (milk, egg white, and wheat), and three insect venoms (honeybee, wasp, and
      Polistes). RESULTS: Eight subjects (0.7%; mean age +/- SD, 123 +/- 9.28 months)
      had positive SPT responses to latex. No children showed allergic reactions to
      latex. One or more positive SPT responses to aeroallergens were present in 340
      children (28.9%); one or more positive SPT responses to food allergens were
      present in 26 (2.2%); one or more positive SPT responses to aeroallergens, food
      allergens, or both were present in 353 (30.0%); and one or more positive SPT
      responses to one or more insect venoms were present in 43 subjects (3.7%).
      Significant (p < 0.05) risk factors associated with latex sensitization included:
      positive SPT responses to aeroallergens, food allergens, or both; a positive
      response to one or more insect venoms; a positive response to mite, milk, egg
      white, wheat, honeybee venom, wasp venom, Polistes venom, or a combination
      thereof; and increased age. CONCLUSION: This report shows a very low prevalence
      of latex sensitization with an absence of clinical symptoms to latex. This study
      demonstrates a significant association between latex sensitization and the
      presence of one or more positive SPT responses to aeroallergens, food allergens,
      or both; one or more positive SPT responses to one or more insect venoms; and
      increased age.

PMID- 9600499
TI  - Association of sensitization to Alternaria allergens with asthma among school-age
      children.
AB  - BACKGROUND: Molds in the Alternaria genus, normally found on outdoor vegetation,
      produce some of the most common fungal allergens to elicit a skin test response.
      OBJECTIVES: The objectives of this study were to evaluate a serum assay for IgE
      antibodies to Alternaria allergens and to establish the prevalence of
      sensitization to Alternaria allergens among children and adults enrolled in
      epidemiologic studies of asthma. In addition, the significance of sensitization
      to Alternaria allergens as a risk factor for asthma was compared with that of
      sensitization to indoor allergens or pollens. METHODS: Using the Pharmacia
      Capsulated Hydrophobic Carrier Polymer (CAP) system, we have evaluated the
      significance of Alternaria allergens by using sera from several epidemiologic
      studies of asthma. RESULTS: Comparisons between serum assays and skin test
      results suggest that this in vitro assay yields results similar to those for
      traditional RASTs and is as sensitive as skin prick testing. In each of the
      groups studied, sensitization to Alternaria allergens was more common among
      asthmatic than control subjects, and in two studies the relationship was highly
      significant. Alternaria allergens were significantly associated with asthma in
      middle schools in Charlottesville, Virginia and Los Alamos, New Mexico but not in
      Albemarle County, Virginia. Logistic regression analysis of the results for the
      three schools identified an association between sensitization to Alternaria
      allergens and asthma independent of, but not as strong as, that found between
      sensitization to indoor allergens and asthma (p < 0.001). CONCLUSIONS: The
      Pharmacia CAP system is a useful tool for measuring specific IgE to Alternaria
      allergens. Although not as important as sensitization to dominant local indoor
      allergens, sensitization to Alternaria allergens appears to be a significant
      independent risk factor for asthma in children in some locations of the United
      States.

PMID- 9600500
TI  - Nasal congestion secondary to allergic rhinitis as a cause of sleep disturbance
      and daytime fatigue and the response to topical nasal corticosteroids.
AB  - BACKGROUND: Allergic rhinitis (AR) is a frequent disease affecting up to 20% of
      the population. AR causes a hypersensitivity reaction, which results in inflamed
      nasal mucosa and nasal congestion. Negative pressure generated during inspiration
      in the nasal airway secondary to nasal congestion may lead to nasal collapse,
      airway obstruction, and an increased number of sleep microarousals. Sleep
      disturbances and microarousals can detrimentally affect daytime energy levels,
      mood, and daytime function. It is unknown whether treatment directed to reduce
      congestion may reduce these microarousals, sleep problems, and, consequently,
      associated daytime fatigue. OBJECTIVE: We sought to determine whether reducing
      nasal congestion with nasal steroids will reduce sleep complaints and daytime
      sleepiness. METHOD: We enrolled 20 subjects in a double-blind, placebo-controlled
      study using Balaam's Design. Patients were treated with topical nasal
      corticosteroids or placebo. Subjective data were collected by use of a daily
      diary, which focused on nasal symptoms, sleep, and daytime sleepiness. RESULTS:
      The results demonstrated that nasal congestion and subjective sleep improved
      significantly in the topical corticosteroid-treated subjects but not in the
      placebo group. Sleepiness improved, but not significantly (p = 0.08). CONCLUSION:
      Often, people with perennial allergies may attribute their daytime fatigue to
      causes such as the side effects of medications, when in fact, the fatigue may be
      a result of nasal congestion and associated sleep fragmentation. Decreasing nasal
      congestion with nasal steroids may improve sleep, daytime fatigue, and the
      quality of life of patients with AR.

PMID- 9600501
TI  - Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis:
      effects after controlled ragweed pollen challenge in an environmental exposure
      unit.
AB  - BACKGROUND: Allergic rhinitis affects nearly one in 10 Americans. Cetirizine is a
      newer once-daily selective H1-antagonist. In traditional clinical trials,
      cetirizine has been shown to be safe and effective for the treatment of seasonal
      and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: To
      better characterize the efficacy and onset of action of cetirizine in a more
      controlled but clinically relevant setting, this agent was compared with
      loratadine and placebo in patients with symptomatic seasonal allergic rhinitis
      undergoing controlled pollen challenge in an environmental exposure unit (EEU).
      METHODS: This was a double-blind, randomized, parallel-group study. After
      screening, patients were exposed to ragweed pollen (primed) in the EEU (up to six
      exposures), and those with qualifying symptom scores were randomized to
      controlled pollen exposure (two periods of 5.5 to 6.5 hours over 2 days) and once
      daily treatment with 10 mg cetirizine (n = 67), 10 mg loratadine (n = 67), or
      placebo (n = 68). The mean ragweed pollen level was 3480 +/- 350 grains/m3
      (standard deviation). The primary efficacy variables were the total symptom
      complex (TSC) and the major symptom complex (MSC) scores. Symptoms were evaluated
      every half hour in the EEU throughout the study. RESULTS: Cetirizine produced a
      36.7% mean reduction in TSC scores overall versus 15.4% with loratadine and 12.0%
      with placebo (p < or = 0.01). Cetirizine also produced a 37.4% mean reduction in
      MSC scores overall versus 14.7% with loratadine and 6.7% with placebo (p < or =
      0.01). Onset of action as assessed by reductions in TSC and MSC scores versus
      placebo was evident within 1 hour with cetirizine (p < or = 0.02) and 3 hours
      with loratadine (p < or = 0.03). The incidence of treatment-related side effects
      was similar among groups, with headache reported most commonly in each group.
      CONCLUSION: Cetirizine is well tolerated and effective in reducing symptoms of
      seasonal allergic rhinitis in patients undergoing controlled pollen challenge.

PMID- 9600502
TI  - Asthma and increased bronchial responsiveness in elite athletes: atopy and sport
      event as risk factors.
AB  - BACKGROUND: High prevalence of bronchial hyperresponsiveness and asthma has been
      found in cross-country skiers. There is limited evidence that asthma and
      bronchial responsiveness would be common also in athletes with summer events.
      OBJECTIVES: The objective of this study was to investigate occurrence of and risk
      factors for increased bronchial responsiveness and asthma in elite athletes with
      summer events and to compare their results with those of control subjects.
      METHODS: Forty-nine speed and power athletes (mean age 21.1 years, range 16 to
      31), 71 long-distance runners (mean age 26.6 years, range 16 to 39), 42 swimmers
      (mean age 18.6 years, range 14 to 25), and 45 control subjects (mean age 26.7
      years, range 21 to 37) were studied. The subjects answered questionnaires and
      were given a resting spirometric examination, a skin prick test, and a histamine
      challenge test. RESULTS: Current asthma (current asthmatic symptoms and increased
      bronchial responsiveness) was observed in 14% (22 of 162) of the athletes and in
      2% (1 of 45) of the control subjects (p = 0.041). Total asthma (current asthmatic
      symptoms and increased bronchial responsiveness or physician-diagnosed asthma)
      occurred in 23% (37 of 162) of the athletes and in 4% (2 of 45) of the control
      subjects (p = 0.0048). Atopy according to skin prick test results was found in
      48% (77 of 162) of the athletes and in 36% (16 of 45) of the control subjects
      (not significant). Clinical pollen allergy (positive skin test reaction to pollen
      and symptoms of rhinoconjunctivitis) was significantly (p = 0.037) more common in
      athletes than in control subjects. Atopic athletes showed significantly more
      often increased bronchial responsiveness, current asthma, and total asthma than
      nonatopic athletes (p = 0.011, p = 0.0049, and p < 0.0001, respectively), and the
      odds ratios of increased bronchial responsiveness and asthma increased with the
      number of positive skin test reactions. After adjustment for confounding factors,
      the odds ratio for the occurrence of current asthma was 5.49 (95% confidence
      interval 0.56 to 53.7) in speed and power athletes, 2.88 (0.30 to 27.7) in long
      distance runners, and 10.8 (1.10 to 106.0) in swimmers compared with control
      subjects. The adjusted odds ratios for the occurrence of total asthma were 3.56
      (0.62 to 20.5) in speed and power athletes, 6.01 (1.19 to 30.2) in long-distance
      runners, and 5.89 (1.00 to 34.5) in swimmers. CONCLUSIONS: Asthma is more common
      in highly trained athletes than in control subjects. Asthma is especially common
      in elite swimmers, but the risk of asthma is increased also in long-distance
      runners. Increased bronchial responsiveness and asthma are strongly associated
      with atopic disposition and its severity in elite athletes.

PMID- 9600503
TI  - A dose-response relationship between exposure to cockroach allergens and
      induction of sensitization in an experimental asthma in Hartley guinea pigs.
AB  - OBJECTIVE: An indoor allergen, cockroach allergen (CRa) has been partly
      implicated in the rising prevalence of inner-city asthma. This study investigates
      a dose-response relationship of exposure to CRa with the degree of sensitization
      and with airway inflammation through the use of our established guinea pig asthma
      model. METHODS: Four groups of Hartley guinea pigs were exposed to aerosolized
      saline (control) and three dose levels of CRa: low-dose, 0.5 mg (LD); medium
      dose, 5 mg (MD); or high-dose, 25 mg (HD), nebulized twice a day, 5 days per
      week, for 4 weeks. The development of anaphylactic antibodies was measured by
      both allergy skin test and passive cutaneous anaphylaxis assay. Animals were
      challenged with CRa 5 days after the last sensitization, and specific airway
      resistance was measured continuously by a double-chamber plethysmograph while
      animals were in the conscious state. The inflammatory cells in bronchoalveolar
      lavage fluid (BALF) and the contractile responses of tracheal rings were analyzed
      in vitro at 24 hours after CRa challenge. RESULTS: The anaphylactic antibodies to
      CRa were detected in the CRa-sensitized animals by allergy skin test. Passive
      cutaneous anaphylaxis titers of IgG1a-like antibody were zero in control, 1:2 in
      LD, 1:40 in MD, and 1:160 in HD. Total leukocytes in BALF were increased by CRa
      challenge in all three CRa-sensitized groups compared with control (p < 0.0001).
      The tracheal rings from CRa-sensitized guinea pigs constricted upon addition of
      incremental doses of CRa challenge in vitro in a dose-responsive manner (p <
      0.0001). The leukocytosis in BALF and the anaphylactic contractile responses of
      the tracheal rings in CRa-sensitized groups were correlated to the levels of CRa
      to which the groups had been exposed during sensitization (p < 0.001). CRa
      provoked increase in SRaw was noted in all three groups of the CRa-sensitized
      guinea pigs compared with control (p < 0.01). Yet, among CRa-sensitized groups, a
      greater increase in specific airway resistance was noted in the LD group but not
      in the HD CRa group. CONCLUSIONS: The development of anaphylactic cockroach
      sensitivity in guinea pigs was dependent on the levels of CRa exposure during
      sensitization, and the CRa-sensitized animals showed antigen-specific airway
      inflammation along with airway smooth muscle contractions. However, the severity
      of bronchospasm in conscious animals was not in agreement with the degree of CRa
      sensitivity.

PMID- 9600504
TI  - Determinant analysis of IgE and IgG4 antibodies and T cells specific for bovine
      alpha(s)1-casein from the same patients allergic to cow's milk: existence of
      alpha(s)1-casein-specific B cells and T cells characteristic in cow's-milk
      allergy.
AB  - In an effort to clarify the etiology of milk allergy from the standpoint of
      allergen-specific immune reactions, we investigated the determinants of IgE,
      IgG4, and T cells specific for bovine alpha(s)1-casein from the same individual
      patients by using its synthetic peptides and cyanogen bromide-digested fragments.
      Alpha(s)1-casein is a major allergen in cow's milk, and its unique conformation
      enabled us to investigate the determinants of antibodies without consideration
      about missing the reactivities because of conformational changes. Nine patients
      were selected as subjects from among 129 milk-sensitive infants screened by ELISA
      to assess the anti-alpha(s)1-casein IgE levels in their sera. By using ELISA for
      epitope mapping, a C-terminal region of alpha(s)1-casein was identified as a
      common binding site for IgE from all of these patients, whereas those for anti
      alpha(s)1-casein IgG4 were located in multiple regions of alpha(s)1-casein. We
      determined the specificities of seven alpha(s)1-casein-specific T-cell lines
      established from peripheral blood mononuclear cells of two of the patients. These
      T cells have been shown to secrete IL-4. All of the T-cell lines had different
      specificities to alpha(s)1-casein. However, a common amino acid residue use was
      found among the determinants of various T-cell lines from each patient. The
      results suggest that patients allergic to cow's milk have characteristic B cells
      recognizing a limited region of alpha(s)1-casein and secreting alpha(s)1-casein
      specific IgE. These B cells may interact particularly with T cells recognizing
      determinants with a common structure.

PMID- 9600505
TI  - Comparative studies of functional and binding assays for IgG anti
      Fc(epsilon)RIalpha (alpha-subunit) in chronic urticaria.
AB  - BACKGROUND: Recent data suggest that a subpopulation of patients with chronic
      urticaria have an autoimmune disorder that is caused by the presence of
      antibodies to the IgE receptor. The actual incidence of these antibodies is
      uncertain. OBJECTIVE: We sought to assess the incidence of autoimmunity to the
      IgE receptor in patients with chronic urticaria and to compare functional and
      binding assays. METHODS: We isolated skin mast cells and studied a large number
      of patient sera (68) for their ability to activate these cells and isolated
      basophils. We then compared the results with those obtained by immunoblotting
      using cloned alpha-subunit of the IgE receptor. RESULTS: Sera from patients with
      chronic urticaria released significant histamine (> 15% of basal) on incubation
      with basophils (48%) and mast cells (46%). By immunoblotting we obtained positive
      results in 64% of subjects tested and also identified a small subpopulation that
      is active on cells but does not bind Fc(epsilon)RIalpha. CONCLUSION: Our data
      suggest that approximately 45% to 50% of patients with chronic urticaria have a
      cutaneous autoimmune disorder. Immunoblotting may provide a rapid screening
      method for anti-Fc(epsilon)RIalpha detection in such patients.

PMID- 9600506
TI  - IL-3, IL-5, granulocyte-macrophage colony-stimulating factor receptor alpha
      subunit, and common beta-subunit expression by peripheral leukocytes and blood
      dendritic cells.
AB  - BACKGROUND: IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM
      CSF) receptors consist of cytokine-specific alpha-subunits, which associate with
      a shared signalling common beta-subunit (beta(c)) to form a high-affinity
      complex. The expression of IL-3, IL-5, and GM-CSF is upregulated in atopic
      inflammation, and these cytokines are thought to contribute to pathology through
      mechanisms that include eosinophil activation. OBJECTIVE: We sought to examine
      the distribution of receptor expression between cells relevant to allergic
      inflammation from individual subjects and to compare atopic and nonatopic
      individuals. METHODS: Peripheral blood was obtained from atopic and nonatopic
      volunteers. Cytokine-receptor expression was examined by flow cytometry with
      monoclonal antibodies specific for alpha-subunits and beta(c) in combination with
      phenotypic markers for eosinophils, basophils, neutrophils, dendritic cells,
      monocytes, and T cells. RESULTS: Using a ligand-independent system, we confirmed
      the cellular distribution of IL-5Ralpha, IL-3Ralpha, and GM-CSFRalpha. IL-3Ralpha
      and GM-CSFRalpha were detected on high-affinity IgE receptor blood dendritic
      cells. Beta(c) expression was detected on basophils, eosinophils, neutrophils,
      and, at low levels, on monocytes and dendritic cells. There was intense staining
      of basophils for IL-3Ralpha relative to IL-5Ralpha, GM-CSFRalpha, and beta(c),
      whereas eosinophil-staining intensity was similar for IL-3Ralpha, IL-5Ralpha, GM
      CSFRalpha, and beta(c). There were no significant differences between atopic and
      nonatopic subjects in cytokine-receptor staining. CONCLUSION: IL-3Ralpha and GM
      CSRalpha are shown on a newly defined population of Fc(epsilon)RI-high dendritic
      cells. The intense staining of basophils for IL-3Ralpha, relative to that of IL
      5Ralpha and GM-CSFRalpha, is in contrast to eosinophils from the same subjects
      and may explain the higher sensitivity of basophils to IL-3 compared with IL-5
      and GM-CSF. We found no evidence for downregulation of receptor expression in
      atopic compared with nonatopic subjects, suggesting that these receptors remain
      accessible as potential targets for therapeutic intervention in atopic allergic
      disease.

PMID- 9600507
TI  - Degranulation of human basophils by picomolar concentrations of IL-3, IL-5, or
      granulocyte-macrophage colony-stimulating factor.
AB  - In most secretory cells, an increase in the cytosolic free Ca2+ concentration
      ([Ca2+]i) is associated with the exocytosis response. In this study we have
      evaluated the effect of thapsigargin on histamine release from purified (70% to
      97% pure) human basophils of nonallergic donors. Thapsigargin (2 micromol/L), by
      inhibiting the uptake of Ca2+ in the stores of the endoplasmic reticulum, leads
      within 1 minute to a gradual increase in [Ca2+]i in human basophils. Incubation
      of basophils with thapsigargin by itself induced only a very small release of
      histamine (5.6% +/- 1.8%). However, under suboptimal conditions of stimulation
      with other agonists, preincubation of basophils with thapsigargin significantly
      enhanced histamine release. Most strikingly, addition of thapsigargin made
      basophils extremely sensitive for histamine release induced by IL-3 (maximum
      histamine release, 71% +/- 7%), IL-5 (maximum histamine release, 43% +/- 8%), or
      granulocyte-macrophage colony-stimulating factor (GM-CSF) (maximum histamine
      release, 57% +/- 10%). These cytokines by themselves did not induce histamine
      release in purified basophils. The effect of thapsigargin was mimicked to a
      limited extent by addition of platelet-activating factor. We conclude that
      depletion of the Ca2+ stores may be a critical event in the activation of
      receptor-mediated histamine release in human basophils.

PMID- 9600508
TI  - Superior biologic activity of the recombinant bee venom allergen hyaluronidase
      expressed in baculovirus-infected insect cells as compared with Escherichia coli.
AB  - BACKGROUND: Hyaluronidase (Hya) is one of several allergens in honeybee venom.
      Its cDNA sequence was recently described. OBJECTIVE: We sought to express
      recombinant Hya in prokaryotic and eukaryotic systems and to compare it with
      natural (n)Hya for biologic activity. METHODS: In Escherichia coli Hya was
      produced as inclusion body 6 x His-fusion protein. In baculovirus-infected insect
      cells expression was obtained by cotransfection of linearized Bac-N-Blue DNA and
      pMelBac transfer vector into Spodoptera frugiperda cells. RESULTS: Enzymatic
      activity of Hya from the baculovirus system was equal to nHya, and that of the
      enzyme expressed in E. coli was only 20% to 30% of nHya. In vitro IgE binding was
      similar in nHya and the enzyme from baculovirus but markedly lower in Hya
      expressed in E. coli. CONCLUSIONS: Biologic activity of Hya expressed in
      baculovirus-infected insect cells was comparable with that of the natural enzyme,
      indicating a native-like conformation of the recombinant protein. In contrast,
      the enzyme expressed in E. coli as an inclusion-body protein and reconstituted in
      vitro reached only 20% to 30% of the activity of nHya.

PMID- 9600509
TI  - Analysis of T-cell activation after bronchial allergen challenge in patients with
      atopic asthma.
AB  - BACKGROUND: T helper cells are a heterogeneous group of cells that have
      phenotypic and functional differences. Activated T helper cells have been found
      in peripheral blood after allergen challenge of subjects with atopic asthma, but
      the phenotypes of specific T helper subpopulation involved remains to be
      identified. OBJECTIVE: To characterize the T cell activation markers that may be
      regulated by allergens, we analyzed peripheral blood lymphocytes obtained before
      and after allergen challenge from subjects with atopic asthma. METHODS: We
      analyzed the distribution of the cell surface activation markers, interleukin 2
      receptor (IL-2R) and major histocompatibility complex class II antigens (MHC II)
      among T helper subpopulations classified as naive (CD45RA) or memory (CD45RO)
      phenotypes. Nine adult subjects with atopic asthma underwent bronchoprovacative
      allergen inhalation and isocapnic cold air hyperventilation (ISH) challenge
      followed by serial spirometry. Peripheral blood mononuclear cells (PBMC) were
      isolated at baseline and 2 and 24 hours after challenge. Four-color flow
      cytometry was used to analyze the expression and distribution in vivo of IL-2R
      and MHC II activation markers on naive and memory T cell subsets after challenge.
      RESULTS: At 2 and 24 hours after allergen challenge, there was a significant
      increase in the CD45RO+IL-2R+ T helper cells compared with baseline (mean +/- SE,
      baseline, 12.5% +/- 1% versus 2 hours, 18.1% +/- 1% and 24 hours, 17.8% +/- 2%, p
      < 0.025). MHC II expression was not significantly increased after challenge on
      naive and memory T helper cells and coexpression of IL-2R and MHC II was only
      found in a small proportion of CD45RO+ T helper cells (2.7% +/- 1%). No changes
      of IL-2R or MHC II expression on T helper subsets were observed after ISH
      challenge in the same patients. We also found that 31% to 46% of T helper cells
      coexpress CD45RA and CD45RO simultaneously, and upregulation of IL-2-R and MHC II
      expression occurs only on those T helper cells that express CD45RO. CONCLUSIONS:
      We have found that T helper cells express both CD45RA and CD45RO isoforms, which
      suggests the existence of a transitional phenotype among naive and memory T
      helper cells in peripheral blood. In subjects with atopic asthma, our in vivo
      analysis characterizes two populations of activated memory T helper cells based
      on the expression of IL-2R or MHC II surface molecules after allergen challenge.

PMID- 9600510
TI  - Specific IgE to isocyanates: a useful diagnostic role in occupational asthma.
AB  - BACKGROUND: Isocyanates are the most frequent cause of occupational asthma in
      industrialized countries. OBJECTIVE: We sought to investigate the utility of
      specific IgE measurement in the diagnosis of isocyanate-induced asthma. METHODS:
      Fifty-eight of 101 patients referred for investigation were diagnosed as having
      isocyanate-induced occupational asthma by means of history, serial peak flow
      records, and bronchial provocation tests. Specific IgE antibodies to toluene
      diisocyanate:human serum albumin (HSA), diphenylmethane diisocyanate:HSA, and
      hexamethylene diisocyanate: HSA were measured in all patients by Phadebas RAST.
      RESULTS: Twenty patients had a RAST ratio of 2 or greater to at least one
      isocyanate. Thirteen (28%) of the 46 patients with a positive provocation test
      response had a RAST ratio of 2 or greater, and nine (20%) had a RAST ratio of 3
      or greater. Raising the RAST cut-off from 2 or greater to 3 or greater reduced
      its sensitivity but increased the specificity of the test to 100%. RAST
      measurement was most likely to be positive within 30 days of exposure. Serial
      measurements suggested that the half-life of the IgE antibodies was approximately
      6 months. Evidence of cross-reactivity between isocyanate RAST responses was
      found in eight subjects. CONCLUSION: Specific IgE to isocyanates is a more
      specific than sensitive index of occupational asthma. With a RAST score of 3 or
      greater, it is wholly specific and therefore diagnostic of isocyanate-induced
      asthma. The sensitivity of specific IgE measurement is highest when blood is
      taken less than 30 days from last exposure, which is consistent with the observed
      half-life.

PMID- 9600511
TI  - Bronchial challenge tests in baker's asthma.

PMID- 9600512
TI  - Current global status of carotid artery stent placement.
AB  - Our purpose was to review the current status of carotid artery stent placement
      throughout the world. Surveys were sent to major interventional centers in
      Europe, North and South America, and Asia. Information from peer-reviewed
      journals was also included and supplemented the survey. The survey asked various
      questions regarding the patients enrolled, procedure techniques, and results of
      carotid stenting, including complications and restenosis. Of the centers which
      were sent surveys, 24 responded. The total number of endovascular carotid stent
      procedures that have been performed worldwide to date included 2,048 cases, with
      a technical success of 98.6%. Complications that occurred during carotid stent
      placement or within a 30-day period following placement were recorded. Overall,
      there were 63 minor strokes, with a rate of occurrence of 3.08%. The total number
      of major strokes was 27, for a rate of 1.32%. There were 28 deaths within a 30
      day postprocedure period, resulting in a mortality rate of 1.37%. Restenosis
      rates of carotid stenting have been 4.80% at 6 mo. Endovascular stent treatment
      of carotid artery atherosclerotic disease is growing as an alternative to
      vascular surgery, especially for patients that are at high risk for standard
      carotid endarterectomy. The periprocedural risks for major and minor strokes and
      death are generally acceptable at this early stage of development.

PMID- 9600513
TI  - Success with carotid stenting: a stroke of good luck or the wave of the future?

PMID- 9600514
TI  - Calculation of the aortic valve gradient from the left ventricular-femoral and
      aortic-femoral pairs of pressure waveforms.
AB  - Accurate measurement of the transaortic gradient is important in the invasive
      assessment of the significance of aortic stenosis. The mean gradient obtained
      from simultaneous left ventricular and aortic pressure recordings is the gold
      standard, but requires two central catheters. We hypothesized that a gradient
      calculated by subtracting the aortofemoral from the ventriculofemoral gradient
      would reproduce the ventriculoaortic gradient. In 24 patients sequential
      recordings of the aortofemoral, ventriculofemoral, and ventriculoaortic pressures
      pairs were obtained. The calculated ventriculoaortic gradient was obtained by
      subtracting the aortofemoral gradient from the ventriculofemoral gradient. Both
      of these gradients were measured by computer, using a systolic ejection period
      between the crossovers of the upslope and downslope of the left ventricular
      waveform with the femoral waveform. The ventriculoaortic gradient calculated
      using this technique correlated closely with the gradient measured by two central
      catheters (R = 0.99). This technique is accurate and does not require two central
      catheters.

PMID- 9600515
TI  - Alchemy in the cath lab: creating a gold standard.

PMID- 9600516
TI  - Accuracy of computer-based quantification of aortic valve stenosis.
AB  - In patients with aortic valve stenosis, the quantification of stenosis is usually
      performed using fluid-filled catheters and a computerized calculation program.
      The aim of this study was to determine the accuracy of this technique in
      comparison to the manual planimetry of the area between the curves of a
      simultaneous registration, using a multitip micromanometer catheter. The study
      was performed in 19 patients, in whom left and right heart catheterization was
      warranted. Systolic left ventricular and aortic peak pressures were significantly
      overestimated using a fluid-filled catheter (206 +/- 35 vs. 199 +/- 37 mm Hg, P =
      0.0003, and 148 +/- 18 vs. 143 +/- 21 mm Hg, P = 0.0052). However, peak-to-peak
      pressure gradients were identical comparing both techniques (58 +/- 31 vs. 56 +/-
      32 mm Hg, r = 0.983). The mean pressure gradients and aortic valve areas based on
      simultaneous measurements of left ventricular and aortic pressures by
      micromanometer catheters were identical to the values determined by a computer
      based program using fluid-filled catheters (54 +/- 21 vs. 52 +/- 21 mm Hg, r =
      0.923, P < 0.05, and 0.75 +/- 0.25 vs. 0.77 +/- 0.25 cm2, r = 0.935). Thus, the
      conventional use of fluid-filled catheters and of a computerized calculation of
      aortic valve area is valid for quantification of aortic stenosis in patients with
      sinus rhythm and without significant aortic regurgitation.

PMID- 9600517
TI  - Balloon mitral valvuloplasty: our experience with a modified technique of
      crossing the mitral valve in difficult cases.
AB  - The efficacy and safety of percutaneous transvenous mitral commissurotomy
      performed by the Inoue technique is well known. In cases with critical mitral
      stenosis and when there is abnormal bulge of the interatrial septum, the usual
      direct method of crossing the mitral valve may not be successful. In such cases
      alternative over-the-wire techniques to cross the mitral valve have been
      advocated by various authors. In this report of 32 cases, we present our
      experience with the modified and simplified version of over-the-wire technique of
      crossing the mitral valve in technically difficult cases. This technique involves
      direct positioning of a pigtail Inoue wire into the left ventricle through the
      Mullin sheath followed by introduction of an Inoue catheter over the wire. The
      mitral valve could be crossed in 30 cases (93.75%). There were no major
      complications attributable to this technique. Frequent ventricular premature
      beats (100%) and episodes of nonsustained ventricular tachycardia (90%) were seen
      in most of the cases. We conclude that our modification of the over-the-wire
      technique is safe, effective, and does not require any additional accessories.
      Using this technique, percutaneous transvenous mitral commissurotomy could be
      performed, even in difficult cases wherein the conventional method of crossing
      the mitral valve has failed.

PMID- 9600518
TI  - Another how-to pointer for Inoue balloon mitral valvuloplasty.

PMID- 9600519
TI  - Position control of intravascular Doppler guidewire: concept of a tracking
      indicator and its clinical implications.
AB  - Intracoronary Doppler ultrasound guidewires (DGW) utilize a wide ultrasound beam
      combined with a measurement of the spectral peak velocity to estimate the spatial
      peak velocity within a blood vessel. However, the spectral peak velocity may
      underestimate the true spatial peak velocity if the DGW is not properly
      positioned. The purpose of this study was to find a Doppler-derived parameter
      that would aid in the optimal positioning of the DGW within the vessel lumen. We
      studied the relationship between the time-averaged, spectral-peak velocity (APV)
      and the normalized first Doppler moment (M1/M0) to develop a DGW position
      indicator and demonstrate its clinical utility. In vitro, heparinized, human
      whole blood with a hematocrit of 45% was directed from a reservoir via a roller
      pump into four serially connected straight silicone tubes of known diameter (2.5,
      3.0, 3.5, 4.0 mm). A DGW was inserted into the tubes where simultaneous APV and
      M1/M0 measurements were obtained for flow rates ranging from 49 to 316 ml/min.
      Optimal positioning of the DGW was identified at the position where maximum APV
      and M1/M0 were obtained. With optimal positioning the correlation between APV and
      M1/M0 was good (APV = 1.62 M1/M0 + 5.0; R2 = 0.98). Importantly, this correlation
      showed no dependence on the tube diameter. In vivo, in four patients APV and
      M1/M0 measurements were obtained in 16 coronary artery segments in one left
      anterior descending, two circumflex, and two right coronary arteries. In 10
      vessel segments, there was no discrepancy between the measured and expected M1/M0
      after positioning the DGW with help of the Doppler signal quality only. In six
      vessel segments, repeat DGW positioning using M1/M0 was necessary, yielding an
      average increase of APV of 20% (7-38%). We conclude that DGW positioning can be
      optimized using the correlation between APV and M1/M0 as a reference. For any
      given APV value, there is a corresponding expected value for M1/M0 under the
      condition of optimal positioning. Any discrepancy between the measured and
      expected values for M1/M0 then indicates suboptimal positioning.

PMID- 9600520
TI  - Coronary artery injection technique: a quantitative in vivo investigation using
      modern catheters.
AB  - To date, there have been no quantitative in vivo assessments of contrast volumes
      and injection rates using modern high flow catheters during coronary angiography.
      Contrast volumes (n = 554), injection durations (n = 563), and injection rates (n
      = 498) were collected during 88 cardiac catheterizations. With increasing
      cathetersize (6, 7, and 8 French), injection volume increased (P < 0.0001),
      duration decreased (P < 0.0001), and rate increased (P < 0.0001). Compared with
      injections into the right coronary artery, left coronary artery injections were
      larger (7.1 +/- 0.1 cc vs. 4.8 +/- 0.1 cc, p < 0.0001), longer (3.6 +/- 0.05 sec
      vs 3.0 +/- 0.07 sec, P < 0.0001) and faster (2.1 +/- 0.04 cc/sec vs. 1.7 +/- 0.06
      cc/sec, P < 0.0001). Patients with a significant stenosis in the left main or
      proximal right coronary artery received less contrast (P < 0.0001) more slowly (P
      < 0.0001) over a similar duration of injection (P = NS). When collaterals arose
      from the injected artery, angiographers injected more contrast (P < 0.001) over a
      longer period (P < 0.0001) more slowly (P < 0.0001). Catheter size and the
      injected vessel's location and anatomy significantly affect coronary
      catheterization injection technique.

PMID- 9600521
TI  - Aortic aneurysm following primary balloon angioplasty and secondary endovascular
      stent placement in the treatment of native coarctation of the aorta.

PMID- 9600522
TI  - Stenting coarctation of the aorta: forget ye not--better is the evil of good.

PMID- 9600523
TI  - Fluoroscopy and selective angiography of left ventricular assist system inflow
      cannula as a method of detecting cannula entrapment.
AB  - Left ventricular assist systems have become an important tool as a bridge to
      cardiac transplantation. Malfunction of these devices often leads to clinical and
      hemodynamic deterioration. One potential complication is the obstruction of the
      inflow cannula secondary to remodeling of the left ventricular cavity. We report
      two cases where fluoroscopy and selective angiography were used to visualize the
      orientation and obstruction of the inflow cannula when echocardiographic findings
      were indeterminant.

PMID- 9600524
TI  - Successful redeployment of an unexpanded coronary stent.
AB  - We report on treatment of a patient in whom failure to deploy the distal portion
      of a Palmaz-Schatz stent occurred but was not recognized. After an unstable
      course, the patient underwent repeat coronary angiography, at which time the
      stent was rewired and redilated. Full deployment of the stent with restoration of
      TIMI grade 3 flow was achieved. The putative cause of the problem, incomplete
      deployment of the stent because of inadvertent advancement of the stent delivery
      sheath, should be avoided, and needs to be recognized if it occurs. Crossing and
      redilating the stent is possible, although technically difficult.

PMID- 9600525
TI  - Focal stent collapse in a patient with systemic sclerosis.
AB  - We report a patient with systemic sclerosis having implantation of a 35 mm
      beStent with immediate success but developing angina at follow-up. A focal stent
      collapse with focal hyperplasia in and outside the stent was documented by
      ultrasound after 2 mos. A 14mm Palmaz-Schatz stent was successfully deployed into
      the collapsed beStent, with good 6-mo angiographic result. The stent collapse was
      probably due to unequal distribution of radial forces and possibly reactive
      hyperplasia in this unique patient with systemic sclerosis.

PMID- 9600526
TI  - Characteristics of coronary flow velocity in constrictive pericarditis.
AB  - A 50-yr-old man developed constrictive pericarditis following an episode of acute
      pericarditis. Cardiac catheterization revealed a typical early diastolic dip and
      plateau configuration in both the right and left ventricular pressure curves. The
      coronary flow velocity pattern determined using an intracoronary Doppler
      guidewire showed an abrupt decrease in peak velocity at early diastole and
      followed by plateau until late diastole, the so-called dip and plateau
      configuration. After a successful pericardiectomy, cardiac catheterization no
      longer showed the dip and plateau configuration, but the early diastolic dip in
      the coronary flow velocity persisted probably because of infiltration of the
      organic involvement into the myocardium.

PMID- 9600527
TI  - Simultaneous percutaneous treatment in hypertrophic obstructive cardiomyopathy
      and coronary artery disease: a case report.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) is an established therapy
      for coronary artery disease (CAD), whereas percutaneous transluminal septal
      myocardial ablation (PTSMA) is becoming increasingly significant in the therapy
      of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). We
      report the first ever simultaneous treatment, in a 62-yr-old patient, of
      significant HOCM and a 75% LAD stenosis from which the septal branch to be
      occluded stemmed. Using a double wire technique, first the septal branch was
      occluded through a fractional injection of 4 ml absolute alcohol, thus ablating
      the hypertrophied septal myocardium with reduction of the left ventricular
      outflow tract (LVOT) gradient at rest from 80 to 9 mmHg. Following this, the LAD
      stenosis was dilated and stented. Complications, in particular a trifascicular
      block or ventricular dysrhythmia, did not occur during the hospital stay. To
      conclude, combined PTSMA and PTCA may be considered as a therapeutic alternative
      to a combined surgical intervention in individual cases of symptomatic HOCM and
      CAD, provided that the potential complications are taken into account.

PMID- 9600528
TI  - Hemodynamic rounds series II: the LVEDP.

PMID- 9600529
TI  - Entrapment of angiographic catheter in the right coronary artery: a trap for the
      nonexperienced operator.
AB  - A case of angiographic catheter entrapment in the right coronary artery during
      coronary angiography in a patient with excessive tortuosity of the right iliac
      artery is described. Alternative manipulations in order to avoid this problem are
      presented.

PMID- 9600530
TI  - Treatment of in-stent restenosis with high speed rotational atherectomy and IVUS
      guidance in small <3.0 mm vessels.
AB  - The management of in-stent restenosis remains a subject for debate because no one
      revascularization option is considered the most appropriate. Since a high
      restenosis rate still occurs after repeat balloon angioplasty, new techniques are
      attempted in order to reduce this rate. A combination of high speed rotational
      atherectomy (HSRA) and adjunctive balloon angioplasty is likely to achieve good
      results. In small (<3.0 mm diameter) vessels, the risk of interaction between the
      burr and the stent increases. We thus used intravascular ultrasound (IVUS)
      guidance in the treatment of in-stent restenosis with HSRA in small <3.0 mm small
      diameter vessels. Nine patients with in-stent restenosis in small vessels were
      referred for repeat angioplasty. Initial IVUS examination was used to assess the
      minimal stent struts diameter and to guide the burr size selection. A combination
      of HSRA and additional balloon angioplasty was performed under IVUS and
      angiographic guidance. Mean angiographic reference diameter was 2.25 +/- 0.35 mm
      and mean stent struts diameter was 2.38 +/- 0.20 mm. Burr size was selected
      approximately 0.5 mm smaller than stent struts diameter and ranged from 1.75 to
      2.5 mm, with a 0.88 +/- 0.12 mean burr/artery ratio (range 0.71, 1.08). In two
      patients, a second larger burr was used. In 4/9 patients, the burr size chosen
      under IVUS guidance was close to angiographic MLD at stent implantation and thus
      larger than what would be used without IVUS guidance. Additional balloon
      angioplasty was decided in all cases, using a 1.1 +/- 0.15 balloon/artery ratio.
      No complication occurred. Mean relative gain in minimal lumen diameter (MLD) was
      94 +/- 90% after HSRA and 54 +/- 34% after balloon angioplasty (total relative
      gain 180 +/- 100%). IVUS guidance allowed safe management of in-stent restenosis
      in small vessels using combination of HSRA and balloon angioplasty. Long-term
      follow-up and comparison with other techniques are necessary to assess whether
      this technique should be used routinely.

PMID- 9600532
TI  - The hydrophilic guidewire: the poor man's laser for chronic total coronary
      occlusions for the good and for the bad.

PMID- 9600531
TI  - Recanalization of chronic coronary occlusions using a new hydrophilic guidewire.
AB  - Chronic total occlusion remains a relative contraindication and the main cause of
      failure of coronary angioplasty. Previously available hydrophilic guidewires had
      numerous limitations. The Crosswire is a new 0.014" hydrophilic nitinol guidewire
      which can be accommodated by very-low-profile balloon catheters and has a
      shapeable and highly radiopaque platinum-iridium coiled tip. This guidewire was
      used in 55 patients with 56 chronic coronary occlusions in which recanalization
      by conventional guidewires had failed. Clinical success was 79%. Coronary
      perforation occurred in two cases, one of them requiring pericardiocentesis for
      tamponade. These results illustrate the usefulness of this new guidewire in the
      treatment of chronic total occlusions.

PMID- 9600533
TI  - Distal coronary artery perforation resulting from the use of hydrophilic coated
      guidewire in tortuous vessels.
AB  - We describe our experience with the ChoiCE PT (Boston Scientific Corporation, MN)
      guidewire, which resulted in perforation of the distal coronary artery in two
      instances. This newly introduced guidewire differs from earlier guidewires in its
      ability to cross lesions in tortuous arteries. However, when it buckles deep in
      the coronary artery, perforation can easily result. While the ChoiCE PT guidewire
      is a useful addition to our armamentarium in interventional procedures, it should
      be treated with care.

PMID- 9600534
TI  - Ticlopidine after stenting: "Render unto Caesar that which belongs to Caesar".

PMID- 9600535
TI  - Re Grodman et al.

PMID- 9600536
TI  - Re Erenberg et al.

PMID- 9600537
TI  - Left coronary artery to left ventricular fistula can result in a coronary steal.

PMID- 9600538
TI  - Choice of contrast in left main coronary disease.

PMID- 9600539
TI  - Dressler-like syndrome after percutaneous mitral balloon valvuloplasty
      pericarditis?

PMID- 9600540
TI  - 6F TECHSTAR application as a bailout for partially deployed 8F PROSTAR.

PMID- 9600541
TI  - Myoclonus and epilepsy in childhood: 1996 Royaumont meeting.
AB  - Sudden and brief involuntary movements of central nervous system (CNS) origin
      called myoclonus may be cortical (motor strip), thalamocortical (thalamocortical
      loop) or reticular (caudal reticular formation). Epileptic, cortical and
      thalamocortical myoclonus are combined with a spike which, when it is focal,
      needs back-averaging to be demonstrated. Negative myoclonus due to lapse of tone
      can only be demonstrated during antigravidic posture and may be combined with
      either a slow wave or the second, positive component of a polyspike-wave.
      Epileptic myoclonus must be distinguished from epileptic spasms and tonic
      seizures, and from non-epileptic myoclonus, tics, tremor and chorea. Myoclonus
      may occur in partial symptomatic (mainly Rasmussen and dysplasia), cryptogenic
      (frontal) or idiopathic (negative myoclonus in CSWS) epilepsy. Generalized
      myoclonus is part of inborn errors of metabolism, non-progressive encephalopathy
      (mainly Angelman) and idiopathic epilepsy (juvenile and infantile benign and
      severe forms, and myoclonic-astatic epilepsy). Carbamazepine, vigabatrin and
      eventually lamotrigine may worsen myoclonus whereas it may be improved by
      benzodiazepines, valproate, lamotrigine, zonisamide and piracetam according to
      etiology. Pathophysiology must take in account maturation processes, lesions and
      genetic predisposition. However, precise mechanisms remain unknown and only
      hypotheses can be proposed, that could clarify the age-related EEG and clinical
      expression of the various syndromes.

PMID- 9600542
TI  - Regional and age specific effects of zolpidem microinfusions in the substantia
      nigra on seizures.
AB  - GABAergic (gamma-aminobutyric acid) transmission in the substantia nigra pars
      reticulata (SNR) is critical for seizure control. The SNR effects on seizures are
      site-specific within the SNR and developmentally regulated. These age- and site
      specific effects may be due to differential regional distribution and
      functionality of SNR GABA(A) receptor sites. We investigated the role of
      GABA/benzodiazepine (BZD) receptors in the SNR in the control of seizures as a
      function of age. In adult rats, we determined the effects of bilateral zolpidem
      (an agonist of the BZD1 receptor site) microinfusions in the anterior or in the
      posterior SNR (SNRanterior or SNRposterior, respectively) on flurothyl-induced
      clonic and tonic-clonic seizures. In SNRanterior, zolpidem microinfusions were
      anticonvulsant but ineffective in SNRposterior against clonic seizures.
      Microinfusions of zolpidem in SNRposterior or above SNR, did not alter the
      threshold to clonic seizures. SNR microinfusions of zolpidem did not alter the
      threshold to tonic-clonic flurothyl-induced seizures. In 15 day old (PN 15) rats,
      the SNR microinfusions of zolpidem had anticonvulsant effects on clonic and tonic
      clonic seizures. There was no regional specificity. Microinfusions of zolpidem
      above the SNR, did not alter the threshold to clonic or tonic-clonic seizures.
      Our data demonstrate that the BZD1 binding sites are involved in the SNR control
      of flurothyl seizures in adult and PN 15 male rats.

PMID- 9600543
TI  - Induction of convulsive seizures by acoustic priming in a new genetically defined
      model of epilepsy (Noda epileptic rat: NER).
AB  - Noda epileptic rat (NER) is a mutant rat, found in a Crj: Wistar colony, which
      exhibits a tonic clonic convulsion spontaneously about once per 30 h from 14
      weeks of age. We performed modified acoustic priming, that is, repeated weekly
      sound stimulations from 3 weeks of age. In addition, characteristics of
      audiogenic seizure (AGS), and ictal/interictal electroencephalograms (EEGs) were
      examined. We also studied the effect of repeated weekly stimulations from 14
      weeks of age on AGS susceptibility in another NER. From 9 weeks of age, the NER
      primed from 3 weeks of age had a high incidence (100%) of AGS: a typical seizure
      was composed of sudden wild running and/or jumping (WRJ) followed by clonic or
      tonic-clonic convulsion. The severity and the duration of the AGS were
      intensified and prolonged with an increase in age, respectively. By contrast, the
      NER repeatedly stimulated from the age of 14 weeks, rarely showed AGS (20-40(%).
      The majority of the seizures in this NER were WRJ. The cortical and hippocampal
      EEG during the tonic convulsion showed a low-voltage spike-wave (5-7 Hz). This
      evolved into a high-amplitude spike- or polyspike-waves associated with the
      clonic convulsion. Immediately after cessation of the seizures, the EEG showed a
      flattening or diffuse slowing. In interictal EEG analysis, sporadic spikes
      predominantly in the hippocampus and spike-wave bursts in both the cortex and
      hippocampus occurred from 11 and 20 weeks of age, respectively. These results
      indicate that AGS susceptibility in NER can be induced consistently by modified
      acoustic priming and this rat strain is a new genetic model useful for
      experimental studies of human epilepsy.

PMID- 9600544
TI  - Effect of physical exercise on kindling development.
AB  - The relationship between epilepsy and exercise is a subject of controversy and
      needs more investigation. We report a study of the effect of physical activity on
      the development of amygdala kindling in rats. To analyze the acute and chronic
      effects of exercise on kindling development, 45 rats were divided randomly into
      three groups. The first group (acute group, n=15) was submitted to a daily bout
      of aerobic exercise (40 min running on the treadmill at 20 m/min) and kindling
      stimulated 1 min post-exercise; the second group (chronic group, n=15) was
      submitted to an aerobic training program (40 min running on the treadmill at 20
      m/min, 7 days per week, for 45 days) and then submitted to the same procedure as
      the first group (daily bout of aerobic exercise -- 40 min running on the
      treadmill at 20 m/min and kindling stimulated 1 min post-exercise); and the third
      group (n=15) served as control. All groups were kindling stimulated until they
      reached stage 5 of kindling. The number of stimulations required to reach stage 5
      was statistically higher for the chronic exercise group when compared to the
      acute exercise group and the control group. A longer time spent in stage 1 and a
      shorter after-discharge duration in stage 1 was observed in the acute and chronic
      exercise groups in relation to the control group. This finding suggests that
      chronic physical exercise inhibits development of amygdala kindling in rats.

PMID- 9600545
TI  - Anoxia during kainate status epilepticus shortens behavioral convulsions but
      generates hippocampal neuron loss and supragranular mossy fiber sprouting.
AB  - In rats, this study determined the impact of systemic hypoxia during late kainate
      induced status epilepticus on hippocampal neuron loss and mossy fiber sprouting.
      Non-fasted Sprague Dawley rats were prepared as follows: Naive controls (n=5);
      rats placed 2 min in a hypoxia chamber (hypoxia only; n=6); rats that seized for
      more than 6 h from kainic acid (KA-status; 12 mg/kg; i.p.; n=7); and another KA
      status group placed into the hypoxia chamber 75 min after the convulsions started
      (KA-status/hypoxia; n=16). All rats, except for half of the KA-status/hypoxia
      animals, were perfused 2 weeks later (short-term). The other 8 KA-status/hypoxia
      rats were perfused after 2 months (long-term). Hippocampal sections were studied
      for neuron densities and aberrant mossy fiber sprouting at three ventral to
      dorsal levels. Fascia dentata (FD) mossy fiber sprouting was quantified as an
      increase in the inner minus outer molecular layer (IML-OML) gray value (GV)
      difference. Behaviorally, KA-status/hypoxia rats had a shorter duration of
      convulsive status epilepticus than KA-status animals without anoxia. Hippocampal
      sections showed that compared to controls: (1) hypoxia-only rats showed no
      differences in ventral neuron densities and neo-Timm's stained IML-OML GVs; (2)
      KA-status rats had decreased CA3 densities and a non-significant increase in
      ventral IML-OML GV differences; and (3) KA-status/hypoxia short-term animals
      showed decreased hilar, CA3 and CA1 densities and increased ventral IML-OML GV
      differences. Compared to KA-status/hypoxia short-term rats, long-term animals
      showed no differences in ventral hippocampal neuron densities, but middle and
      dorsal sections demonstrated increased IML-OML GV differences and animals were
      observed to have spontaneous limbic epilepsy. These results indicate that rats
      exposed to kainate-induced status epilepticus for over 1 h and then a hypoxic
      insult had a shorter duration of convulsive status, decreased hippocampal neuron
      densities and greater FD mossy fiber sprouting than controls and the amount of
      neuronal damage and sprouting was slightly more than animals subjected to 6 h of
      kainate-induced status. This supports the hypothesis that a physiologic insult
      during status can shorten the convulsive episode, but still produce hippocampal
      pathology with a number of clinical and pathologic similarities to human mesial
      temporal lobe epilepsy (MTLE).

PMID- 9600546
TI  - The anticonvulsant zonisamide scavenges free radicals.
AB  - Zonisamide (ZNS) is effective in animal models of epilepsy and epileptic
      patients. The free radical scavenging activities of ZNS were analyzed by using
      electron spin resonance. ZNS, in the mmolar range, scavenged hydroxyl and nitric
      oxide radicals in a dose-dependent manner. This suggests that the mechanism of
      antiepileptic effect of ZNS may involve protection of neurons from free radical
      damage and stabilization of neuronal membranes.

PMID- 9600547
TI  - Electrocorticographic changes during generalized convulsive status epilepticus in
      soman intoxicated rats.
AB  - Generalized convulsive status epilepticus (GCSE) is the most common and
      potentially most damaging form of status epilepticus (SE). It has been previously
      reported, in both human GCSE and animal models of GCSE, that the
      electroencephalographs (EEGs) and electrocorticographs (ECoGs) recorded during
      GCSE contain an ordered sequence of five identifiable patterns: discrete seizures
      (phase 1), waxing and waning ictal discharges (phase 2), continuous ictal
      discharges (phase 3), continuous activity with flat periods (phase 4), and
      periodic epileptiform discharge on a flat background (phase 5). In this paper, we
      report the same pattern of ECoG changes in 15 rats exposed to soman, an
      acetylcholinesterase (AChE) inhibitor. Phase 1 was observed in 12 of 15 animals,
      but phases 2-5 were recorded in all the animals. Taken together, these findings
      suggest that the sequence of EEG changes is independent of the initiating cause,
      represent a common electrical response to GCSE, and reflect a common underlying
      neurochemical mechanism.

PMID- 9600548
TI  - The child's foot: principles of management.

PMID- 9600549
TI  - Resection for symptomatic talocalcaneal coalition.
AB  - Over a 10-year period, 20 persistently symptomatic talocalcaneal tarsal
      coalitions were treated with resection. These cases were reviewed at an average
      of 29 months after treatment. Preoperative computed tomography (CT) scans were
      obtained in 17 of 20 feet. Good or excellent clinical results were obtained in
      77% of patients with resection of coalitions involving one third or less of the
      total joint surface. Increasing age in this group was not a contraindication to
      surgery. Four patients had an uncommon varus deformity and were treated with
      resection. Overall this subgroup had a poorer prognosis.

PMID- 9600550
TI  - Idiopathic toe walking: a comparison of treatment methods.
AB  - Eighty children with idiopathic toe walking (ITW) were examined 2-8 years
      (average, 34 months) after initial presentation to compare outcomes [passive
      ankle dorsiflexion (DF) and parental satisfaction] after three treatment
      modalities: observation, cast/brace treatment, or surgical triceps surae
      lengthening. Overall, 32% had a family history of ITW, 28% were born prematurely,
      and 16% had psychomotor delay. Forty-eight untreated patients showed little
      change in passive ankle DF at final follow-up, and only 25% of parents were
      satisfied with the child's gait. Compared with untreated children,
      casting/bracing appeared to offer no significant improvement in ankle DF or
      parental satisfaction. Surgical treatment was performed in 15 children with more
      severe equinus contractures. Triceps surae lengthening resulted in significantly
      improved ankle DF and 67% parental satisfaction (p < 0.05). Toe walking may
      persist after all standard treatment methods, even in the absence of significant
      Achilles contracture.

PMID- 9600551
TI  - Subtalar arthroereisis for the correction of planovalgus foot in children with
      neuromuscular disorders.
AB  - We studied the results of 140 STA-peg arthroereisis procedures performed for the
      treatment of planovalgus foot deformity in 78 ambulatory children with
      neuromuscular disease. Patient age at surgery ranged from 2 + 2 to 14 + 11 years,
      with a mean of 7 + 9 years. Patients were followed up for an average of 4 + 6
      years. The ultrahigh-molecular-weight polyethylene (UHMWPE) STA-peg implant is
      inserted laterally into the subtalar joint such that its stem extends inferiorly
      into the calcaneus and its collar abuts the inferior surface of the lateral
      process of the talus, thereby blocking excessive valgus tilt of the calcaneus.
      All but five patients (nine feet) had concomitant soft-tissue procedures to
      balance the foot. The talocalcaneal angle and the talar declination angle were
      measured on lateral radiographs preoperatively, postoperatively, and at the
      latest follow-up visit. Patients were evaluated for the presence of pain and
      hindfoot valgus deformity. Satisfactory results were achieved in 135 (96.4%)
      feet. Results were unsatisfactory in one foot of each of five patients who had
      bilateral procedures; one was painful, and four developed varus. The STA-peg was
      removed in these five patients. No infections or adverse tissue reactions to the
      STA-peg implant were observed. STA-peg arthroereisis, combined with satisfactory
      muscle-balancing procedures, can predictably achieve control of planovalgus foot
      deformity in children with neuromuscular disorders and may obviate the need for
      long-term orthotic wear.

PMID- 9600552
TI  - Duration of immobilization after percutaneous sliding heel-cord lengthening.
AB  - Heel-cord lengthening is commonly performed for contractures in neuromuscular
      disease. Immobilization after this procedure has ranged from 3 to 8 weeks. A
      three-part study was performed to determine adequate length of immobilization.
      Sixteen rabbits had surgical transection of the right gastrocsoleus tendon in
      phase 1. Healing was allowed for 1, 3, 5, or 7 weeks. Tendons were then studied
      by magnetic resonance imaging (MRI), mechanical testing, or histologic section. A
      marker for healing was determined by MRI. Seven children underwent percutaneous
      sliding heel-cord lengthening (PSHCL) in phase 2. Healing was studied by MRI.
      Based on the marker from phase 1, adequate healing occurred at 3 weeks. Thirty
      one children underwent PSHCL for neuromuscular contracture in phase 3. Cast
      immobilization was maintained for 3 weeks (group 1) and for >3 weeks (group 2).
      There was no evidence of rupture or progressive lengthening after cast removal in
      either group.

PMID- 9600553
TI  - Botulinum toxin A compared with stretching casts in the treatment of spastic
      equinus: a randomised prospective trial.
AB  - Conservative therapies for equinus in cerebral palsy may help to postpone calf
      surgery in younger children. This study reports a prospective randomised trial of
      intramuscular botulinum toxin A (BtA) as an alternative to serial casting in 20
      children with a dynamic component to calf equinus. Outcome was assessed in the
      short term to show the effect of one treatment cycle. Assessments were by
      clinical examination, video gait analysis, and three-dimensional gait analysis.
      BtA was of efficacy similar to that of serial casting. Tone reduction in the BtA
      group allowed a more prolonged improvement in passive dorsiflexion, which may
      allow more opportunity for increase in muscle length. Gait analysis showed an
      improved mean ankle kinematic pattern in a subsection of both groups, which was
      maintained at 12 weeks in the BtA group, whereas the cast group relapsed. There
      were fewer side effects in the BtA group. Median time to reintervention was
      similar.

PMID- 9600554
TI  - Incidence and type of hindfoot deformities in patients with low-level spina
      bifida.
AB  - In a consecutive series of 174 children with low-level spina bifida, there was
      hindfoot deformity in 263 of the 348 feet; 86 were in equinus, 108 were in
      calcaneus, 41 were in valgus, 20 were in varus, and eight had convex pes valgus.
      Surgery was performed on 222 (64%) feet. The deformities were symmetric in 114
      children. Spasticity causing deformity necessitated surgery in only 44 feet.
      Calcaneus deformity in the foot is considerably more common in patients with L4
      lesions, and in these circumstances, muscle imbalance is clearly a major factor.
      However, many patients with calcaneus deformity had L5 or sacral lesions. This
      suggests that muscle imbalance is not so important a factor as has been thought
      in the causation of deformity in the lower limb in myelomeningocele.

PMID- 9600555
TI  - Muscle and tendon size relationships in a paralyzed chick embryo model of
      clubfoot.
AB  - Clubfoot is a birth defect that may be related to muscle weakness or imbalance.
      The purpose of this study was to examine the relationships among muscle and
      tendon size and embryonic motility in a paralyzed chick embryo model of clubfoot
      and arthrogryposis. Decamethonium bromide, a neuromuscular blocking agent, was
      administered to a series of embryos in five dosage groups, producing a cohort of
      embryos with various degrees of paralysis and atrophy of tendons and muscle.
      Embryonic movement frequency was monitored, and after death in late gestation,
      the cross-sectional areas of the calf musculature and the gastrocnemius tendon
      proximal to the ankle were measured histologically. Significant correlations were
      found between embryonic motility and both muscle (r2 = 0.52) and tendon (r2 =
      0.77) areas. In addition, a significant correlation (r2 = 0.74) was found between
      muscle and tendon areas, suggesting that a measurement of one may be used to
      predict the other.

PMID- 9600556
TI  - Rotation fasciocutaneous flap for neglected clubfoot: a new technique.
AB  - Skin necrosis and wound problems complicate surgical release of severe neglected
      clubfoot. This is primarily the result of excessive tension on the skin edges and
      a poor understanding of the abnormal vascular anatomy in clubfoot. We report a
      technique of primary skin closure by using a local-rotation fasciocutaneous flap.
      Posteromedial skin incision is taken. Posterior tibial artery perforators
      supplying the medial flap and saphenous vein are preserved. After soft-tissue
      release and correction of deformity, a defect appears in the posteromedial part
      of wound. Horizontal backcut is taken at proximal part of the incision and entire
      medial fasciocutaneous flap is rotated inferiorly to cover the defect. Triangular
      defect appearing proximally is sutured primarily or covered with skin graft.
      Primary uncomplicated wound healing was achieved within 2 weeks in all 20 rigid
      and neglected clubfeet (1-7 years) operated on with this technique. This flap is
      scientifically logical, technically easy, and ensures primary wound healing.

PMID- 9600557
TI  - An independent assessment of two clubfoot-classification systems.
AB  - We conducted an independent assessment of two clubfoot-classification systems. In
      a blinded trial, two orthopaedists scored 55 feet by using the classification
      systems developed by Pirani et al. and by Dimeglio et al. Thirty-seven of the
      feet were also scored by a physical therapist. By using the 10-point
      classification described by Pirani, the two physician examiners tallied total
      scores that were within one point of one another 89% of the time. The mean
      difference between the scores assigned by the two examiners was 0.6 points. For
      the 20-point classification described by Dimeglio et al., total scores tallied by
      the two physician examiners were within two points of one another 91% of the
      time. The mean difference between the scores assigned by the two physician
      examiners was 1.4 points. Correlation coefficients were 0.90 (p = 0.0001) for the
      Pirani classification, and 0.83 (p = 0.0001) for the Dimeglio classification.
      Correlation coefficients were much lower for the first 15 feet scored and were
      also lower when the therapist's scores were included. Overall, both
      classification systems had very good interobserver reliability after the initial
      learning phase.

PMID- 9600558
TI  - Osteochondritis dissecans of the talus during childhood and adolescence.
AB  - Between 1985 and 1996, our Service treated 18 cases of osteochondritis dissecans
      of the talus in children and adolescents. The lesion is more frequent during
      childhood than previously thought. Different theories about the etiology of the
      lesion and the various treatments used are discussed. The outcome was
      satisfactory in most cases. We consider that, with the exception of type IV
      Berndt and Harty lesions, preliminary treatment should be conservative, which
      gave good results in our study. Surgical treatment should be reserved for
      patients with an unsatisfactory evolution with orthopaedic treatment, with
      lesions with thick sclerotic edges, or for patients with loose intraarticular
      fragments.

PMID- 9600559
TI  - The too-long anterior process calcaneus: a report of 39 cases in 25 children and
      adolescents.
AB  - We observed 39 feet with a "too-long" anteromedial process of the calcaneus
      (TLAP) in 25 children and adolescents. The abnormality was diagnosed from
      symptoms (ankle sprains or persistent ankle or foot pain) in 33 cases. Six cases
      of TLAP were noted on radiographs taken of the patient's opposite, asymptomatic
      foot. Initial treatment by 3 weeks of strapping failed in seven of seven cases,
      and 3-6 weeks of primary plaster immobilization failed in 10 of 25 feet. Primary
      immobilization treatment failed in 17 of 33 symptomatic feet. Resection of the
      TLAP provided good results in 14 of 15 feet when used as a secondary procedure
      after failure of immobilization treatment and in one foot in which it was used as
      primary treatment. We believe that this abnormality is an anatomic variant that
      becomes symptomatic because of inversion stress with impingement of the
      abnormally long process between talus and cuboid.

PMID- 9600560
TI  - Gigantism of the foot: our experience in seven cases.
AB  - We report our experience in seven patients with congenital gigantism of the foot
      with the following diagnoses: neurofibromatosis (two), fibrolipomatosis (two),
      Proteus syndrome (two), and idiopathic localized gigantism (one). Our purpose is
      to introduce a new classification of foot gigantism, based on the concept of
      "neuroinduction." In our experience, intraoperative examination and subsequent
      histologic examination show consistently pathologic findings in the plantar nerve
      and its terminal branches in the foot affected by gigantism. Limited surgical
      treatment was used in five patients. To prevent forefoot enlargement and
      recurrence of deformity, we suggest complete ray resection. We evaluated our
      results using radiographs, functional status, and cosmetic considerations.

PMID- 9600561
TI  - Psychosocial development and corrective shoewear use in childhood.
AB  - To assess the short- and long-term psychosocial effects of wearing modified shoes
      during childhood, we compared measures of self-esteem and self-image of 46 adults
      who wore shoe modifications during childhood with 92 adult controls. The treated
      cases characterized their remembrance of the experience through a subjective
      report questionnaire. Those who wore shoe modifications during childhood showed
      lower self-esteem than controls (p < 0.05). In addition, the treated recalled a
      decrease in their self-image (41%), the experience as negative (57%), being
      teased about their footwear (47%), and having their activities limited (41%).
      These findings show that wearing shoe modifications during childhood, in addition
      to being ineffective and unnecessary as demonstrated in prior studies, is a
      negative experience in childhood and is associated with lower self-esteem in
      adult life. Such data suggest that children who wore modified footwear may fall
      into the spectrum of the vulnerable child syndrome.

PMID- 9600563
TI  - Total body irradiation-induced osteochondromata.
AB  - Nine patients developed osteochondromata, a mean of 6 years after total body
      irradiation (TBI) given before bone marrow transplantation for childhood
      leukaemia. This represents 23% of patients receiving TBI during the period from
      1981 to 1989 surviving > or =5 years after bone marrow transplantation. The
      patients were followed up for a mean of 12.5 years from diagnosis of leukaemia
      and a mean of 2.5 years from diagnosis of osteochondromata. No osteochondroma,
      including three lesions removed surgically, showed evidence of malignant change.
      Six patients received growth hormone for irradiation-induced growth hormone
      deficiency, but this did not appear to influence the natural history of the
      osteochondromata. Radiation-induced osteochondromata (RIO) are often multiple and
      are indistinguishable from the more common idiopathic type. The incidence of RIO
      after TBI was higher than that reported after local irradiation.

PMID- 9600562
TI  - Treatment outcome of pelvic sarcomas in young children: orthopaedic and oncologic
      analysis.
AB  - Five children with pelvic Ewing's sarcoma whose age was 6-10 years underwent
      reconstruction after resection of the tumor. One child with a tumor of the ilium
      underwent an iliosacral arthrodesis with allograft. Three patients underwent a
      hip transposition after the resection of the ilium and the upper part of the
      acetabulum. One patient underwent no skeletal reconstruction after the resection
      of the acetabulum and the ilium. Two children are alive 96 and 60 months after
      surgery; however, two died 12 and 21 months after surgery of metastasis, and one
      is alive with metastasis 15 months after surgery. Functional evaluation was
      possible in four patients: one is excellent, and three are fair. After resection
      of the ilium, including the upper part of the acetabulum, a hip transposition can
      be selected. If all the acetabulum is resected, it will be optimal not to do a
      bony reconstruction.

PMID- 9600564
TI  - Infantile hemangiopericytoma of the musculoskeletal system: case report and
      literature review.
AB  - Infantile hemangiopericytoma is an uncommon cause of a soft-tissue mass in the
      neonatal period. Only 86 of these tumors have been reported in the literature.
      Thirty of these were located in the extremities. This review presents a case of
      infantile hemangiopericytoma localized to the knee in an 8-month-old infant.
      Current literature suggests that the majority of these lesions are benign, and
      surgical excision is curative. Recurrence and metastatic disease rarely occur.
      Because 30-50% of infantile hemangiopericytomas occur in the extremities,
      orthopaedic surgeons should be aware of and familiar with this tumor.

PMID- 9600566
TI  - Differential lengthening of the radius and ulna using the Ilizarov method.
AB  - Three patients with relative length discrepancy between the radius and ulna and
      with wrist angular deformity are reported. The Ilizarov apparatus was used for
      correction of the deformity by differential lengthening of the radius and ulna.
      The total lengthening percentages ranged from 21 to 52%. All patients obtained a
      good functional result after surgery with full range of motion of fingers and
      moderate loss of wrist range of motion in two patients. All patients were able to
      achieve primary bone healing.

PMID- 9600565
TI  - Percutaneous epiphysiodesis using transphyseal screws (PETS).
AB  - We describe a new technique of percutaneous epiphysiodesis using transphyseal
      screws (PETS) and our experience with it in 32 cases of limb-length inequality
      and nine angular knee deformities. A subgroup of 18 patients with postfracture
      limb overgrowth formed a clinical model for study of the real efficacy of PETS.
      It proved a reliable method with few complications and many advantages such as
      simplicity of technique, short operating time, rapid postoperative
      rehabilitation, and reversibility. Bone-length inequality decreased from a
      preepiphysiodesis average of 2.47 cm (range, 1.5-4.6) to 0.51 cm at skeletal
      maturity. The tibiofemoral angle reduced from a preoperative average of 7.66
      degrees to 0.86 degrees at maturity. The screws began to exert significant growth
      inhibition within 6 months of insertion, slowing down the distal femoral and
      upper tibial physes by 68 and 56%, respectively. They achieved maximum growth
      retardation over the ensuing 12 months, slowing down the distal femoral physis by
      89% and the proximal tibial physis by 95%. At skeletal maturity, total femoral
      growth was 45% and total tibial growth was 52% that of the normal side. Key

PMID- 9600567
TI  - Effectiveness of brace treatment in early infantile Blount's disease.
AB  - In an effort to determine whether bracing is effective in reversing early
      infantile Blount's disease, 27 patients with Langenskiold stage II disease were
      studied. Ten patients had bilateral disease (two of these patients had stage III
      disease affecting one side). Age at brace initiation averaged 2.1 years (range,
      1.5-3.2). The duration of bracing averaged 9.7 months. Follow-up averaged 5.9
      years. Successful outcomes (improved alignment without the need for osteotomy)
      were achieved in 19 (70%) patients, the majority of them having unilateral
      disease. Of the 37 affected extremities, 24 (65%) had successful outcomes. Eight
      patients (13 extremities) required tibial osteotomies and were classified as
      bracing failures. Of the 10 patients with bilateral involvement, seven (70%)
      required osteotomies for one or both extremities, whereas only one (6%) of 17
      patients with unilateral involvement required osteotomy. Bracing appears to be
      effective in stage II infantile Blount's disease, particularly in those with
      unilateral involvement. Children with bilateral disease are most at risk for
      requiring subsequent corrective osteotomy.

PMID- 9600569
TI  - Can we predict body height from segmental bone length measurements? A study of
      3,647 children.
AB  - It is well known that significant differences exist in the anthropometric data of
      different races and ethnic groups. This is a cross-sectional study on segmental
      bone length based on 3,647 Chinese children of equal sex distribution aged 3-18
      years. The measurements included standing height, weight, arm span, foot length,
      and segmental bone length of the humerus, radius, ulna, and tibia. A normality
      growth chart of all the measured parameters was constructed. Statistical analysis
      of the results showed a very high linear correlation of height with arm span,
      foot length, and segmental bone lengths with a correlation coefficient of 0.96
      0.99 for both sexes. No differences were found between the right and left side of
      all the segmental bone lengths. These Chinese children were found to have a
      proportional limb segmental length relative to the trunk.

PMID- 9600568
TI  - Gait analysis and muscle strength in children with congenital pseudarthrosis of
      the tibia: the effect of treatment.
AB  - Twelve patients with healed congenital pseudarthrosis of the tibia underwent gait
      analysis and muscle strength testing to determine the functional result of
      treatment. Six children younger than 4 years of age presented with pseudarthroses
      (early onset), and six children first fractured at older than 4 years of age
      (delayed onset). Four children with amputations as final treatment for congenital
      pseudarthrosis were studied for comparison. The early-onset group had undergone
      an average of 4.2 surgeries and all required transankle fixation. The delayed
      onset group had undergone an average of 1.5 surgeries, with one child requiring
      fixation across the ankle. Lack of ankle push-off and foot drop occurred in the
      early-onset group. Terminal stance phase ankle power generation was greatly
      diminished in the early-onset group. Total mechanical work performed by the
      affected limb, when compared to the uninvolved contralateral limb, was symmetric
      in delayed-onset patients and reduced by 68% in early-onset patients and by 85%
      in amputees. Gastrocsoleus strength was reduced by 40%. Gait and muscle strength
      of patients with "healed" congenital pseudarthrosis of the tibia are markedly
      disturbed. Early onset of disease, early surgery, and transankle fixation lead to
      an inefficient gait comparable to that of amputees.

PMID- 9600570
TI  - Stature and severity in multiple epiphyseal dysplasia.
AB  - We investigated the stature and radiological findings in 15 patients with
      multiple epiphyseal dysplasia (MED). They were divided into normal-stature and
      short-stature groups according to their body height after 4 or 5 years of age.
      Their stature was not related to the involvement of the spine or epiphyses of
      long tubular bones except for the distal radius. Proximal phalanges and metacarpi
      were shorter in the short-stature group than in the normal-stature group,
      indicating that stature in MED had some relationship to the involvement of the
      wrist and hand. However, some patients in the normal-stature group showed
      involvement of distal radial epiphyses, and some patients in the short-stature
      group did not have stubby fingers. There are thus no clear-cut criteria to
      differentiate between the severe Fairbank type and the milder Ribbing type of
      MED.

PMID- 9600571
TI  - Postnatal development of the human sternum.
AB  - Postnatal development and maturation of the human sternum are highly variable.
      Endochondral ossification centers (sternebrae) form within each cartilaginous
      segment of the sternum, with each center enveloped by a spherical growth plate.
      Within a cartilaginous center there may be either one or two ossification
      centers, those with two centers retaining and reflecting features of their
      bilateral embryonic origin. Malaligned bifid centers are clearly associated with
      rib articulation asymmetry as well. Expansion of individual ossification centers
      progresses within the peripheral cartilaginous domains of the sternum. With
      respect to the rostrocaudal axis, sternebrae form between the costosternal
      articulations. Consistent with the biology of endochondral transition, cartilage
      canals are evident throughout unossified regions of the hyaline matrix. Expanding
      ossification of adjacent sternebrae results in depletion of the common area of
      cartilage between the two sternebrae, and eventually in physiologic
      epiphysiodesis. Fusion of the mesosternebrae reciprocates the initial pattern of
      sternebral ossification site appearance, proceeding in a caudal-to-cranial
      direction. Union of adjacent sternebrae, initiated through a central osseous
      bridge, progresses through anterior, lateral, cephalocaudal, and posterior
      domains to achieve synostosis. Accessory and bifid centers of ossification within
      the same intercostal space coalesce prior to adjoining adjacent sternebrae.
      Manubriosternal fusion is rare due to the presence of a fibrocartilaginous joint
      restricting ossification. The xiphoid process remains connected to the most
      caudal mesosternum via a common zone of hyaline cartilage that ossifies by middle
      to late adulthood. A single pattern of development does not appear fundamental to
      successful growth of the sternum, as morphological variants were common.

PMID- 9600572
TI  - The effect of surgery on the iliac apophysis: an experimental study.
AB  - The effect of surgery on the subsequent growth of the iliac apophysis was studied
      in 30 immature New Zealand White rabbits. Groups of animals were subjected to
      splitting of the iliac apophysis or excision of part of or the whole apophysis.
      These animals were compared to a group with a sham operation. Results showed that
      splitting with subsequent resuturing of the iliac apophysis resulted in normal
      growth in height but increased growth in width and thickness of the iliac bone.
      Excision of one third of the iliac apophysis did not interfere with subsequent
      growth, but excision of two thirds or more of the iliac apophysis resulted in
      retarded growth of the iliac bone. These experimental studies suggest that the
      iliac apophysis can be safely split in the surgical approach to a child's hip.
      Also one third of the iliac apophysis can be safely sacrificed for use as a
      physeal graft or for chondrocyte cultures.

PMID- 9600573
TI  - Use of a modified Bell Tawse procedure for chronic acquired dislocation of the
      radial head.
AB  - We retrospectively reviewed five patients with chronic acquired dislocation of
      the radial head, treated with open reduction and ligament reconstruction with a
      slip of the triceps tendon. Three of the cases were posttraumatic, one was a
      dislocation resulting from a mass-occupying lesion, and one case was caused by
      recurrent radial head subluxation occurring after an initial traumatic episode.
      An ulnar osteotomy was used in one case to allow reduction of the radial head.
      All patients had a good postoperative functional and radiographic outcome,
      without postoperative complications. In two cases, there was slight loss of
      motion in relation to the contralateral extremity. Reconstruction of the annular
      ligament by using a strip of the triceps fascia is a safe and effective treatment
      in the treatment of chronic acquired radial head dislocation.

PMID- 9600574
TI  - Torticollis secondary to posterior fossa tumors.

PMID- 9600575
TI  - Adenosine A1 receptors modulate anxiety in CD1 mice.
AB  - The effect of the selective adenosine A1 receptor agonist 2-chloro-N6
      cyclopentyladenosine (CCPA) was investigated in CD1 mice by the elevated plus
      maze and the light/dark test, two models for measuring anxiety in rodents. CCPA,
      administered i.p., had an anxiolytic effect at 0.3 nmol/kg in the elevated plus
      maze and at 1 nmol/kg in the light/dark test. Brain levels of 22 nM were found
      after administration of 100 nmol/kg CCPA, as measured by ex vivo binding
      experiments. These values are consistent with the occupancy of adenosine A1 but
      not A2 receptors by CCPA, and suggest that the anxiolytic-like action of CCPA may
      be mediated by centrally located adenosine A1 receptors. Both CPT, a selective
      adenosine A1 receptor antagonist, and IBMX, a non-selective adenosine antagonist,
      had an anxiogenic effect in the two tests. It is thus possible that purinergic
      neurons may be involved in the tonic modulation of affective state in mice.

PMID- 9600576
TI  - Selective alpha7-nicotinic agonists normalize inhibition of auditory response in
      DBA mice.
AB  - Abnormal sensory inhibition is a measurable indicator of a sensory processing
      deficit which is observed in schizophrenia, and other disorders, and which may be
      heritable. This deficit has also been observed in certain inbred mouse strains
      where the intensity of the deficit has been correlated with reduction in the
      number of hippocampal alpha-bungarotoxin-sensitive nicotinic receptors. Nicotine
      and certain nicotinic agonists produce brief periods of normal sensory inhibition
      in these mice. Similarly, nicotine also transiently normalizes sensory inhibition
      in schizophrenics. The present study assessed the effects of a novel nicotinic
      partial agonist (GTS-21), selective for the alpha-bungarotoxin site, on sensory
      inhibition in DBA mice, a strain with no sensory inhibition under routine
      experimental conditions. GTS-21 produced a dose-dependent normalization of
      sensory inhibition which was blocked by alpha-bungarotoxin but not mecamylamine.
      In contrast to other nicotinic agonists, normalization of sensory inhibition by
      GTS-21 and two related anabaseine compounds, DMAB-anabaseine and DMAC-anabaseine,
      was observed when administered a second time to the animal, after a 40-min delay.
      Our results indicated that the anabaseine compounds increase sensory inhibition
      through alpha7 nicotinic receptors, and that their ability to act repeatedly on
      these receptors may be less affected by desensitization.

PMID- 9600577
TI  - Effect of pertussis toxin on baclofen- and diphenhydramine-induced amnesia.
AB  - The effect of pretreatment with pertussis toxin at the doses of 0.25 and 0.50
      microg per mouse ICV on the amnesic effect produced by baclofen (0.1 4 mg kg(-1)
      i.p.), diphenhydramine (15-30 mg kg(-1) i.p.) and scopolamine (0.5-5 mg kg(-1)
      i.p.) was investigated in the mouse passive avoidance test. Ten days after a
      single injection of pertussis toxin, baclofen (2 4 mg kg(-1) i.p.) amnesia was
      prevented. By contrast, pertussis toxin had no effect on diphenhydramine- and
      scopolamine-induced amnesia. Pretreatment with pertussis toxin at both doses used
      did not impair motor coordination of the mice, as revealed by the rota-rod test.
      The present results indicate that the activation of pertussis toxin-sensitive G
      proteins represents an important transduction step in memory impairment induced
      by GABA(B) (gamma-aminobutyric acid B) agonists, but not by antihistaminic and
      antimuscarinic drugs.

PMID- 9600578
TI  - Isradipine prevents global and regional cocaine-induced changes in brain blood
      flow: a preliminary study.
AB  - The L-type calcium channel antagonist, isradipine, reduces brain ischemia in
      animal models of ischemic stroke. These effects of isradipine appear more
      pronounced in dopamine (DA) rich brain regions. These same DA-rich brain regions
      have also been shown to be the areas most affected by cocaine-induced ischemic
      changes. Using a novel quantified approach to single photon emission computerized
      tomography, we demonstrated that isradipine pre-treatment prevented cocaine
      induced ischemic changes, especially in these DA-rich brain regions. This is the
      first demonstration that any medication, including isradipine, can prevent the
      ischemic effects of cocaine on brain blood flow. Isradipine may, therefore, be a
      useful therapeutic agent for the prevention of brain ischemia in cocaine addicts.

PMID- 9600579
TI  - Gender-dependent dissociation between oxytocin but not ACTH, cortisol or TSH
      responses to m-chlorophenylpiperazine in healthy subjects.
AB  - m-Chlorophenylpiperazine (m-CPP), a serotonin (5-HT) agonist with some
      selectivity for the 5-HT2C receptor subtype, which is widely used to examine 5-HT
      receptor function in human subjects, has been found to induce oxytocin and
      thyrotropin (TSH) responses in rodents. This study examined whether m-CPP had any
      effect on plasma oxytocin, TSH and aldosterone concentration in healthy
      volunteers using a double-blind, placebo-controlled crossover design. Plasma
      adrenocorticorticotropic hormone (ACTH) and cortisol responses, two generally
      accepted markers of m-CPP-induced 5-HT receptor activation, were measured in
      parallel. Male subjects (n=7) received placebo, 0.25 and 0.5 mg/kg oral m-CPP. In
      female subjects (n=5), the effects of placebo and 0.25 mg/kg m-CPP were studied.
      After placebo, given in the morning, ACTH, cortisol, TSH and aldosterone
      concentrations decreased over time. m-CPP 0.25 mg/kg avoided decreases in ACTH,
      cortisol and TSH concentrations; these responses were significant. At the dose of
      0.5 mg/kg, m-CPP caused increase in ACTH, cortisol, TSH and aldosterone
      concentrations. Significant plasma oxytocin responses were found in female
      subjects only; thus this effect of m-CPP was statistically significantly gender
      dependent. Other responses to m-CPP were similar in male and female subjects. The
      present results suggest that there are clear differences, including dose and
      gender-dependent dissociations, among the 5-HT receptor agonist m-CPP-induced
      neuroendocrine responses.

PMID- 9600580
TI  - Fuels for memory: the role of oxygen and glucose in memory enhancement.
AB  - Recent studies indicate that some aspects of memory can be enhanced by the
      administration of oxygen or glucose. Considering the dependency of glucose
      metabolism upon oxygen supply, the present study predicted that administering a
      combination of 100% oxygen with glucose would have greater memory-enhancing
      effects than when either substance was administered alone. In a placebo
      controlled study, 104 healthy adults were given a glucose or placebo drink, and
      inhaled 100% oxygen or air for 1 min, before carrying out a number of everyday
      memory tasks designed to measure short-term and long-term memory. Results showed
      support for the enhancing effects of oxygen (but not for glucose) on delayed
      recall. These findings are discussed in relation to the possible cholinergic
      properties of oxygen and glucose and the implications for their clinical use.

PMID- 9600581
TI  - Buspirone and lorazepam in the treatment of generalized anxiety disorder in
      outpatients.
AB  - In this double-blind, placebo-controlled 10-week trial, the anxiolytic properties
      of the nonbenzodiazepine buspirone were compared with the benzodiazepine
      lorazepam and placebo in 125 outpatients with generalized anxiety disorder
      according to DSM-III. After a 3- to 7-day wash-out period, patients were
      allocated at random to receive orally 3 x 5 mg buspirone (n=58), 3 x 1 mg
      lorazepam (n=57), or placebo (n=10) over a 4-week period. The study also
      comprised a 2-week taper period and a 4-week placebo-control period to assess the
      stability of clinical improvement. The patient's clinical state was estimated on
      entry and at weekly intervals by general practitioners using the Hamilton Rating
      Scale for Anxiety (HAM-A) and Clinical Global Impression (CGI) assessment and by
      a self-rating scale (State Trait Anxiety Inventory X2=STAI-X2). Lorazepam
      treatment resulted in descriptively, but not significantly, greater improvement
      on the Hamilton Rating Scale for Anxiety during the whole treatment (week 0-4)
      and taper period (week 5, 6) than did buspirone. After treatment with active
      drugs had been discontinued, the 4-week placebo control period showed buspirone
      treated patients to display a stability of clinical improvement, while the
      symptoms of lorazepam-treated patients worsened at week 7-10. Both buspirone and
      lorazepam were more efficacious in reducing anxiety symptoms than placebo during
      the treatment and taper period; however, in contrast to the active drugs
      (buspirone, lorazepam), patients of the placebo group showed further clinical
      improvement during the control period, especially in the HAM-A score, so
      differences between placebo and active drugs became smaller at the end of the
      study.

PMID- 9600582
TI  - Sertindole and dopamine D2 receptor occupancy in comparison to risperidone,
      clozapine and haloperidol - a 123I-IBZM SPECT study.
AB  - The striatal D2 dopamine binding was studied in schizophrenic patients treated
      with the novel atypical antipsychotic drug sertindole (n=10). Comparisons were
      obtained with haloperidol (n=8), clozapine (n=6), risperidone (n=11) and
      untreated healthy controls (n=8) of a dataset which has partly been reported
      previously. 123I-Iodobenzamide (IBZM) single photon emission computerized
      tomography (SPECT) was used for estimation of striatal dopamine D2 receptor
      binding. Sertindole-treated patients exhibited significantly (P < 0.001) lower
      levels of striatal D2 binding (BG/FC ratio:1.28) compared with those treated with
      haloperidol (BG/FC ratio:1.09) and risperidone (8 mg:1.18) but significantly (P <
      0.005) higher levels compared with clozapine (BG/FC ratio: 1.49). However, if
      patients were pretreated with a depot neuroleptic, significantly (P < 0.05)
      higher striatal D2 binding (BG/FC ratio:1.12) has been obtained. Since sertindole
      has been shown to exert distinct clinical efficacy for treatment of positive and
      negative symptoms, our data are indicative that antipsychotic efficacy is not
      associated with a high degree of striatal D2 receptor occupancy in schizophrenic
      patients.

PMID- 9600583
TI  - Nullification of a positive correlation between urinary contents of alpha1
      microglobulin and ulinastatin with intracerebroventricularly administered 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium
      (MPP+) in mice.
AB  - Striatal dopamine contents in C57BL/6J mice were reduced at 24 h after
      intracerebroventricular (ICV) administration of 1-methyl-4-phenyl-1,2, 3,6
      tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) in a dose
      dependent manner. A dose of 1.8 microg MPP+ significantly (P < 0.05) suppressed
      the dopamine contents, whereas a similar dose of MPTP did not. A definite
      positive correlation between urinary contents of alpha1-microglobulin (alpha1M)
      and ulinastatin (UT) existed in normal mice. However, this correlation was
      nullified by ICV administration of 18 and 36 microg MPTP or 1.8 and 18 microg
      MPP+. With 1.8 microg MPTP, a positive correlation between urinary contents of
      alpha1M and UT was displayed. The urine volume, creatinine content, glomerular
      filtration rate, alpha1M and UT contents, and alpha1M/UT ratio of urine collected
      for 24 h post-ICV administration of MPTP or MPP+, were not statistically
      different from those of control mice. Our findings suggest that the central
      effects of MPP+, a neurotoxic metabolite of MPTP, nullify the positive
      correlation between urinary contents of alpha1M and UT without affecting renal
      functions.

PMID- 9600584
TI  - Discriminative stimulus properties of low doses of ethanol in humans.
AB  - Discriminative stimulus properties of low doses of ethanol were evaluated in
      humans using established behavioural drug discrimination procedures. Twenty-five
      moderate drinkers (12 females and 13 males) were trained to discriminate placebo
      from 0.2 g/kg ethanol in 200 ml tonic water mixed with Tabasco sauce and drunk in
      portions of 50 ml every 15 s. Seventeen of the subjects (ten females and seven
      males) were able to reach criterion performance (at least 80% correct responses).
      Generalisation responding across ethanol doses of 0 (placebo), 0.025, 0.05, 0.1
      and 0.2 g/kg was examined the day after training using a procedure in which
      subjects reported the extent to which the test stimulus resembled the training
      dose. At the end of each generalisation session, self ratings of mood changes,
      physiological responses and performance in a working memory and a time estimation
      task were evaluated. Subjects were able to distinguish the three higher doses of
      ethanol from placebo. Self ratings indicated that subjects' ability to
      distinguish ethanol from placebo was related, at the highest dose, to change of
      taste, but to feelings of light-headedness at the lower doses. Ethanol
      administration influenced skin conductance measurements but there was no
      relationship found between changes in skin conductance and the ethanol
      discriminative stimulus. These data suggest a difference in the nature of the
      discriminative stimulus of ethanol between high (training) and low (generalising)
      doses as indicated in the subjective reports.

PMID- 9600585
TI  - Cardiovascular autonomic dysregulation in users of MDMA ("Ecstasy").
AB  - The present study examined resting heart rate variability (HRV; an index of
      parasympathetic tone) and heart rate response to the Valsalva maneuver (Valsalva
      ratio; an index of overall autonomic responsiveness) in 12 repeat users of 3.4
      methylenedioxymethamphetamine (MDMA, "Ecstasy"), and a matched comparison group
      of presumed nonusers. HRV and Valsalva ratio were smaller in users than in
      controls. Three out of 12 MDMA users but no controls had Valsalva ratios below
      1.50, the cut-off for autonomic dysfunction. In several users, there was a total
      absence of post-Valsalva release bradycardia. All MDMA users were polydrug users.
      Parasympathetic cardiovascular tone appears impaired in repeat MDMA users,
      although the ubiquitous problems in such epidemiologic designs (including lack of
      testing before the first use of the drug and confounding with use of other drugs)
      preclude definitive causal interpretations.

PMID- 9600586
TI  - The effect of venlafaxine treatment on the behavioural and neurochemical changes
      in the olfactory bulbectomised rat.
AB  - In the present study, the effect of chronic treatment with venlafaxine on beta1
      and 5-HT2 receptor populations was examined in the frontal cortex of olfactory
      bulbectomised (OB) and sham operated (SO) animals. The effect of these drugs on
      the behaviour of the animals on the elevated plus maze and the "open field" was
      also assessed. Removal of the bulbs resulted in a characteristic increase in
      locomotor activity in the OB animals in the "open field" which was reversed by
      chronic venlafaxine treatment. Venlafaxine produced a slight reduction in the
      number of open arm entries made by the OB animals although this failed to reach
      significance. Maximum change in temperature from baseline, following a single
      dose of 8-OH-DPAT (1.5 mg kg(-1) SC), was used to assess the function of the 5
      HT1A receptors. Chronic venlafaxine treatment had no effect on the hypothermic
      response to 8-OH-DPAT in the present study. A decrease in the affinity of beta1
      adrenoceptors was found following olfactory bulbectomy and this was normalised by
      treatment with venlafaxine. No bulbectomy-induced changes were evident 32 days
      post surgery in beta1-adrenoceptor density; however, chronic treatment with
      venlafaxine significantly reduced the density of these receptors in the OB
      animals. Olfactory bulbectomy did not produce any changes in 5-HT2 receptor
      populations but venlafaxine administration significantly reduced the density of
      these receptors in both SO and OB animals. The findings of the present study
      further validate the usefulness of the OB as an animal model, for the detection
      of antidepressants from a wide variety of classes.

PMID- 9600587
TI  - Withdrawal from a self-administered or non-contingent cocaine binge: differences
      in ultrasonic distress vocalizations in rats.
AB  - After termination of a self-administered cocaine "binge," rats emit ultrasonic
      vocalizations (USVs) and these calls may represent affective distress. The
      present study investigated whether the rates of USVs as indices of withdrawal
      from a period of continuous access, depends on cocaine being self-administered
      versus given non-contingently. Five days after implantation of a jugular
      catheter, triads of rats that were matched for housing, food-training and surgery
      were placed into experimental chambers. The active rats were allowed to acquire
      self-administration of cocaine (0.5 mg) while the two yoked animals passively
      received either cocaine (0.5 mg) or saline according to the active animal's
      pattern of administration. Once the active animal responded at a stable rate over
      3 days, with every third lever press being reinforced by cocaine (FR3), it was
      allowed free access to cocaine (0.5 mg) for 16 h. Subsequently, all animals were
      exposed to 18 air puffs (10 psi) at 0, or 1, 3, 5, 7 and 14 days after the
      "binge". Immediately following the binge, there was no significant difference in
      the rate of startle-induced USVs between the active cocaine group and the yoked
      saline group. However, the yoked or non-contingent cocaine rats emitted
      significantly higher rates of USVs immediately after the last cocaine infusion.
      At the time of the peak increase in USVs, the active and yoked cocaine groups
      were significantly different. For up to 5 days after unlimited cocaine access,
      the active and passive-cocaine groups showed an increase in USVs response when
      compared to the yoked saline group. The emerging increase in USVs and their
      gradual decline observed after termination of a cocaine "binge" can be
      interpreted as an abstinence phenomenon. The non-contingent cocaine appears to be
      highly aversive, as indicated by the immediate significant increase in the rate
      of USVs after termination of a cocaine "binge".

PMID- 9600588
TI  - Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors.
AB  - Evidence from studies with phenylisopropylamine hallucinogens indicates that the
      5HT2A receptor is the likely target for the initiation of events leading to
      hallucinogenic activity associated with LSD and related drugs. Recently, lisuride
      (a purported non-hallucinogenic congener of LSD) was reported to be a potent
      antagonist at the 5HT2C receptor and an agonist at the 5HT2A receptor. LSD
      exhibited agonist activity at both receptors. These data were interpreted as
      indicating that the 5HT2C receptor might be the initiating site of action for
      hallucinogens. To test this hypothesis, recombinant cells expressing 5HT2A and
      5HT2C receptors were used to determine the actions of LSD and lisuride. LSD and
      lisuride were potent partial agonists at 5HT2A receptors with EC50 values of 7.2
      nM and 17 nM, respectively. Also, LSD and lisuride were partial agonists at 5HT2C
      receptors with EC50 values of 27 nM and 94 nM, respectively. We conclude that
      lisuride and LSD have similar actions at 5HT2A and 5HT2C receptors in recombinant
      cells. As agonist activity at brain 5HT2A receptors has been associated with
      hallucinogenic activity, these results indicate that lisuride may possess
      hallucinogenic activity, although the psychopharmacological effects of lisuride
      appear to be different from the hallucinogenic effects of LSD.

PMID- 9600589
TI  - X-linked dominant Charcot-Marie-Tooth disease: nerve biopsies allow morphological
      evaluation and detection of connexin32 mutations (Arg15Trp, Arg22Gln).
AB  - X-linked Charcot-Marie-Tooth neuropathy (CMTX) is caused by mutations in the
      connexin32 gene on Xq13. Because of overlapping morphological and clinical data,
      CMTX patients often meet the criteria of autosomal-dominant CMT2, the neuronal
      type of CMT. Hence, it might be useful to analyse the connexin32 gene in
      suspected CMT2 patients when there is no male-to-male transmission. We selected a
      cohort of 30 patients who were considered having CMT2 on the basis of previous
      clinical and histopathological evaluation. DNA was extracted from paraffin
      embedded sural nerve biopsy samples and screened for connexin32 mutations to
      verify the possible diagnosis of CMTX. In 2 patients mutations were found
      corresponding to amino acid substitutions of arginine for tryptophan in codon 15
      and arginine for glutamine in codon 22 of connexin32. This study illustrates that
      archival material allows genetic classification of suspected CMT cases.
      Furthermore, there is additional proof that connexin32 mutations represent the
      underlying genetic defect in some cases of predominantly neuronal CMT.

PMID- 9600591
TI  - Beta-amyloid(1-40)-induced neurodegeneration in the rat hippocampal neurons of
      the CA1 subfield.
AB  - Small volumes of solutions injected into the hippocampus produce dramatic
      degeneration in dentate gyrus neurons, but not in neurons of the CA1 subfield.
      The aim of the present study was to ascertain whether solutions with different
      fragments of the beta-amyloid protein (Abeta) could produce further degeneration
      in areas beyond the dentate gyrus. It was found that 5 days after injection of an
      aqueous solution containing the Abeta 1-40 fragment into the hippocampus, long
      stretches of the CA1 subfield were either deprived of neurons or most of the
      neurons were degenerating. By contrast, in animals with deposits containing Abeta
      1-28, Abeta 1-42 or water, neuronal degeneration or depletion only occurred in a
      reduced area around the place where the implant needle penetrated the CA1
      subfield. In animals injected with Abeta 1-40, many profiles in the CA1 subfield
      and dentate gyrus were undergoing apoptosis, as seen using preparations processed
      by routine histology or the TUNEL technique for detection of fragmented DNA. In
      addition, there was higher infiltration by ED1-positive, activated microglia
      macrophagic cells in Abeta 1-42 deposits than in deposits of Abeta 1-40. The
      present results suggest that the intrahippocampal injection of toxic Abeta
      fragments produces neuronal degeneration in the rat CA1 subfield when using the
      appropriate protocol, and, thus, can provide an in vivo model to investigate the
      neurotoxic effects of Abeta and for the evaluation of drugs with potential anti
      neurodegenerative activity.

PMID- 9600590
TI  - Apolipoprotein E epsilon4 allele and progression of cortical Lewy body pathology
      in Parkinson's disease.
AB  - To elucidate whether the apolipoprotein E epsilon4 allele (APOE4) affects
      cortical neuropathology in Parkinson's disease (PD), we determined APOE genotypes
      and quantified the densities of cortical Lewy bodies (LBs), amyloid plaques and
      neurofibrillary tangles in 22 autopsy-proven PD cases (12 with dementia; 10
      without dementia) that were not accompanied by Alzheimer's disease. The APOE4
      frequency in the demented patient group was 0.21, which was significantly higher
      than that in Japanese controls (P < 0.04). LB densities in demented PD patients
      were significantly higher than those in non-demented PD patients, despite the
      shorter disease duration in the former. Moreover, plaque density in the temporal
      cortex and LB density in the cingulate cortex were significantly higher in the
      group with APOE4 than in that without the allele. There was no difference in
      tangle density between these two groups. These results suggest that APOE4 may
      influence the increase in the number of cortical LBs and amyloid plaques in PD.
      It is possible that when PD occurs in individuals with APOE4, concomitantly
      evolving cortical LB pathology in a proportion of cases results in limbic
      (transitional) or neocortical-type LB disease.

PMID- 9600592
TI  - Early forms of microtubule-associated protein are strongly expressed in cortical
      dysplasia.
AB  - We report the enhanced expression of early forms of microtubule-associated
      proteins (MAPs) in cortical dysplasia in surgical resections from 17 children
      with intractable epilepsy. Large neurons, which represent one of the
      characteristic cellular features of cortical dysplasia, showed strong
      immunoreactivity for MAP1B, as well as the low-molecular-weight isoform of MAP2
      (MAP2c). In situ hybridization with MAP1B antisense riboprobe showed markedly
      increased hybridization signal intensities in the large neurons, whereas neurons
      in the normal-appearing cortex and most of the normal-sized neurons in the
      dysplastic cortex had faint signals. Because MAP2c and MAP1B are early forms of
      MAPs, which are abundantly expressed in the developing brain and down-regulated
      in the adult, and are thought to be involved in neuronal outgrowth and
      plasticity, our results suggest that the structural remodeling of neuronal
      processes is activated in cortical dysplasia.

PMID- 9600593
TI  - Expression of platelet-derived growth factor after transient forebrain ischemia
      in the gerbil hippocampus.
AB  - The present study was conducted to clarify the role of platelet-derived growth
      factor-B chain (PDGF-B) in neuronal death after ischemia. Transient forebrain
      ischemia was induced in Mongolian gerbils by occluding the bilateral carotid
      arteries for 5 min. We investigated PDGF-B expression in the hippocampus after
      ischemia by immunohistochemistry, Northern blotting and in situ hybridization
      histochemistry. The results showed that PDGF-B is expressed in control CAI and
      CA3 neurons. In CA1, the amount of the PDGF-B transcript immediately increased,
      then disappeared 2 days after ischemia. Delayed neuronal death followed 1 day
      later. However, PDGF-B immunoreactivity in CA1 rapidly decreased and disappeared
      12 h after transient forebrain ischemia, proceeding to delayed neuronal death. In
      contrast, the expression of both PDGF-B protein and the transcript was well
      preserved throughout the study in CA3, which remained viable even after ischemia.
      Accordingly, the selective neuronal susceptibility in the CA1 to ischemia
      corresponded with rapid disappearance of PDGF-B. PDGF-B expression may contribute
      to neuroprotective effect after ischemia.

PMID- 9600594
TI  - Hereditary dentatorubral-pallidoluysian atrophy: ubiquitinated filamentous
      inclusions in the cerebellar dentate nucleus neurons.
AB  - We examined the cerebellar dentate nucleus (CDN) in 16 patients with hereditary
      dentatorubral-pallidoluysian atrophy (DRPLA), one of the neurodegenerative
      diseases caused by expansion of a CAG repeat encoding a polyglutamine tract in
      the disease protein. In all patients, some CDN neurons were found to contain
      ubiquitinated filamentous inclusions in their cytoplasm. On hematoxylin and eosin
      preparations, these filamentous inclusions were eosinophilic, basophilic or
      amphophilic, and were often found in areas of pale cytoplasm. Electron microscopy
      revealed that they consisted of bundles of filaments that were somewhat thicker
      than neurofilaments. These features of the present inclusions were
      indistinguishable from those of skein-like inclusions (SLI) previously described
      in the lower motor neurons in sporadic amyotrophic lateral sclerosis. We conclude
      that SLI can also occur in the CDN in DRPLA and believe that they reflect a
      characteristic pathological process in this disease.

PMID- 9600595
TI  - Accumulation of argyrophilic substances in neuronal cytoplasm of aging groggy
      mutant rat.
AB  - A groggy rat is a single autosomal recessive mutant displaying a movement
      disorder. Using Gallyas-Braak (G-B) staining of sections of brain and spinal cord
      from groggy and Slc:Wistar rats, argyrophilic neurons were seen in some regions
      of the 180-day-old groggy rats. The numbers of these neurons and of the regions
      exhibiting these neurons in groggy rats increased with age. In 730-day-old groggy
      rats, these neurons were especially numerous in the red nucleus,
      reticulotegmental nucleus of pons, intertrigeminal nucleus, facial nucleus, all
      the reticular nuclei of medulla, hypoglossal nucleus, and spinal cord layers 7-9.
      Using electron microscopy, silver grains after G-B staining and immunodeposits
      after staining with an anti-phosphorylated tau antibody, AT8, showed the same
      localization in the lipofuscin granules in the neurons of facial and hypoglossal
      nuclei of 730-day-old groggy rats. However, AT8 immunoreactivity was found not
      only in the lipofuscin granules of the facial and hypoglossal nuclei of the aged
      matched Slc:Wistar rat, but also in those of the G- B-negative cerebellar nuclei
      of groggy and Slc:Wistar rats. These facts suggest that the AT8-immunopositive
      tau in the argyrophilic neurons of aged groggy rats is modified to react with the
      G-B staining.

PMID- 9600596
TI  - Prognostic implication of histopathological, immunohistochemical and clinical
      features of oligodendrogliomas: a study of 89 cases.
AB  - Histopathological, immunohistochemical and clinical parameters were correlated
      with survival in 89 cases of oligodendroglioma (65 patients with grade II and 24
      patients with grade III of the WHO classification). Median survival time and 5
      year survival rate were 3.5 years and 76% for patients with oligodendroglioma
      grade II and 0.875 years and 23% for patients with oligodendroglioma grade III.
      The tumor biopsy specimens were immunohistochemically analyzed for Ki 67 (MIB-1),
      vimentin, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE)
      and synaptophysin. MIB-1 nuclear labeling index ranged from 0.0% to 33.4%;
      vimentin-immunoreactive tumor cells were found in 25 cases. MIB-1 nuclear
      labeling index and vimentin immunoreaction showed a significant statistical
      correlation to the 5-year survival rate of the patients. Tumors with vimentin
      expression (n=25) and/or high MIB-1 labeling index (n=26) had a poorer prognosis
      than tumors lacking vimentin expression (n=57) and/or displaying a low MIB-1
      labeling index (n=56). The expression of immunoreactivity for GFAP (n=53), NSE
      (n=23) and synaptophysin (n=15) appeared to be of no prognostic relevance.
      Patients with gross total tumor resection (n=47) had a median survival time and 5
      year survival rate of 3.3 years and 84% compared to 1.2 years and 42% for
      patients with subtotal resection (n=41). The comparison between patients who
      underwent surgery alone (n=53) and those who had surgery plus postoperative
      radiation therapy showed no significant survival benefit from postoperative
      radiation therapy. In conclusion, tumor grade, MIB-1 labeling index, expression
      of vimentin and the extent of surgery are shown to be of prognostic relevance for
      patients with oligodendroglioma.

PMID- 9600597
TI  - Expression of oncogenic molecules in primary central nervous system lymphomas in
      immunocompetent patients.
AB  - We studied overexpression of p53, Bcl-2, Bcl-6, c-Myc and Mdm2 proteins by
      immunohistochemistry for a total of 27 primary central nervous system B cell
      lymphomas (CNS lymphomas) in immunocompetent patients and one CNS lymphoma in an
      AIDS patient. The expression of Epstein-Barr (EB) virus-encoded small RNA-1 (EBER
      1) was also analysed using in situ hybridisation. Overexpression (more than 20%
      of cells stained) of p53 protein was detected in 8 of 27 immunocompetent cases
      (30%); 6 cases showed a nuclear stain and 2 cases showed cytoplasmic stain
      (nuclear exclusion). Strong Bcl-2 or Bcl-6 immunoreactivity suggestive of
      overexpression was seen, respectively, in 5 (19%) and 6 (22%) cases; 2 cases were
      positive for both immunoreactivities. Interestingly, overexpression of Bcl-2 or
      Bcl-6 was not seen in the cases which showed p53 overexpression (P < 0.03; chi
      square test). EBER-1 expression was not detected in any of the 27 immunocompetent
      cases, but was found in the AIDS-related CNS lymphoma, which also showed an
      overexpression of Bcl-6, but not Bcl-2. None of the cases showed c-Myc or Mdm2
      overexpression. Taken together, it is suggested that CNS lymphoma in
      immunocompetent hosts is a distinct disease that has a different molecular
      profile from those of systemic lymphoma and/or AIDS-related CNS lymphoma.

PMID- 9600598
TI  - Sequential analysis of subacute and chronic neuronal, astrocytic and microglial
      alterations after transient global ischemia in rats.
AB  - Recent experimental investigations have emphasized the importance of assessing
      both acute and chronic histopathological changes occurring after cerebral
      ischemia. The purpose of this study was to evaluate the temporal profile of
      neuronal, astrocytic and microglial alterations within vulnerable regions
      (striatum and CA1 sector of hippocampus) following transient global ischemia.
      Anesthetized Wistar rats underwent 10 min of normothermic (37 degrees C) ischemia
      induced by bilateral carotid ligations plus hypotension (45-50 mm Hg) and were
      allowed to survive for periods ranging from 1 to 10 weeks (n=4-6/group) prior to
      quantitative histopathological analysis. Adjacent sections were examined by
      hematoxylin-and-eosin histopathology, immunostaining for glial fibrillary acidic
      protein, and B4-isolectin immunochemistry for microglia. In the striatum, normal
      neuron counts were first decreased significantly at 2 weeks after the ischemic
      insult. Neuronal loss was associated with the proliferation of reactive
      microglia, which peaked at 1 week. By contrast, reactive astrocytosis displayed a
      more protracted pattern, with peak activation at 2 weeks. In the CA1 hippocampus,
      a decreased number of normal neurons was seen at 1 week post ischemia, together
      with a significant increase in immunoreactive microglia at that time; the latter
      normalized after 2 weeks. Reactive astrocytes in the CA1 hippocampus were
      significantly increased at 1-2 weeks after ischemia. In a subgroup of severely
      injured animals, foci of frank striatal infarction were associated with early and
      severe microglial and astrocytic proliferation at week 4 or later. Finally,
      cerebrovascular changes included endothelial disruption within affected areas.
      These observations document a subacute and chronic sequence of cellular responses
      following brief periods of global ischemia, involving both neurons, glia and
      vascular endothelium.

PMID- 9600599
TI  - White matter alterations following thromboembolic stroke: a beta-amyloid
      precursor protein immunocytochemical study in rats.
AB  - Thromboembolic stroke in rats leads to a well-described pattern of
      histopathological and behavioral abnormalities. However, limited data are
      available in animal models concerning the response of the white matter to embolic
      events. The purpose of this study was to document patterns of white matter
      abnormalities using beta-amyloid precursor protein (betaAPP) immunocytochemistry
      as a marker of axonal damage. Twelve male Wistar rats underwent photochemically
      induced right common carotid artery thrombosis (CCAT) or sham procedures. At 3
      days after CCAT, rats were perfusion-fixed and sections immunostained for the
      visualization of betaAPP or stained with hematoxylin and eosin for routine
      histopathological analysis. As previously described, CCAT produced small
      ipsilateral embolic infarcts and ischemic cell change within gray matter
      structures including the medial cerebral cortex, striatum, hippocampus and
      thalamus. In areas of frank infarction, numerous reactive profiles were observed
      within borderzones of the damaged site. However, betaAPP immunocytochemistry also
      revealed reactive axonal profiles within various white matter tracts including
      the corpus callosum, external capsule and fimbria of the hippocampus. In many
      cases, the presence of axonal damage could not be appreciated with routine
      hematoxylin and eosin staining. These data indicate that CCAT leading to platelet
      embolization to the brain not only produces embolic infarcts but also produces
      more subtle white matter abnormalities. Previously undetected white matter damage
      would be expected to participate in the sensorimotor and cognitive behavioral
      deficits following embolic stroke.

PMID- 9600600
TI  - Immunohistochemical, ultrastructural, biochemical and in vitro studies of a
      pineocytoma.
AB  - Using both tumor specimen and cultured tumor cells, we have studied the
      differentiation of a pineocytoma by light and electron microscopy (EM) and
      immunohistochemical demonstration of glial, neuronal and neuroendocrine markers.
      Only interstitial cells were labeled with anti-glial fibrillary acidic protein
      and anti-S100 protein antibodies. Synaptophysin, neurofilaments and tau labeling
      was found in cells forming the pineocytomatous rosettes. Some cells also bound
      the anti-tryptophan hydroxylase antibody (TPOH), but no staining was seen after
      application of anti-chromogranin A or S-antigen antibodies. EM provided evidence
      for neurosensory differentiation demonstrating the presence of vesicle-crowned
      rodlets, cilia (9+0) and fibrous filaments. In culture, tumor cells proliferated
      slowly and showed positive immunolabeling for vimentin and TPOH. Expression of
      mRNA coding for TPOH, serotonin N-acetyltransferase, hydroxyindole-O-methyl
      transferase and c-myc was found in the tumor using reverse transcriptase
      polymerase chain reaction. These results demonstrate neuronal differentiation of
      this pineocytoma and suggest that the neoplastic pineal cells are capable of
      synthesizing serotonin and melatonin.

PMID- 9600601
TI  - Confocal microscopic localization of anti-myelin-associated glycoprotein
      autoantibodies in a patient with peripheral neuropathy initially lacking a
      detectable IgM gammopathy.
AB  - We report here on a patient with anti-myelin-associated glycoprotein (MAG)
      neuropathy in whom examination of a sural nerve biopsy by multichannel confocal
      microscopy showed a partly overlapping distribution of MAG and IgM deposits in
      myelinated fibers. Our data demonstrate that MAG in Schmidt-Lanterman incisures
      and paranodal loops, as well as some additional HNK-1-positive components of the
      basal lamina, are the major targets of the anti-MAG monoclonal IgM autoantibodies
      in this neuropathy in vivo. Perforation of the basal lamina can allow the
      penetration and binding of anti-MAG IgM inside myelinated fibers. Our results
      support and extend the notion that the production of monoclonal anti-MAG IgM may
      be antigenically driven by MAG molecules and that this process may occur in the
      immunologically privileged environment of the nerve prior to the appearance of a
      genuine gammopathy in serum.

PMID- 9600602
TI  - Abundant minute myotubes in a patient who later developed centronuclear myopathy.
AB  - Centronuclear myopathy (CNM) is a congenital myopathy which manifests itself as a
      severe neonatal (also termed myotubular myopathy), early-onset, or adult form.
      The histological pattern of each is marked by a considerable number of nuclei of
      muscle fibers being internally placed. Owing to their remote resemblance to
      myotubes, and their expression of developmentally regulated proteins, most
      authors now favor the concept that myogenesis is arrested or delayed in this
      disease. We here present two muscle biopsy specimens of a patient with early
      onset CNM, taken at the age of 5 months and 14 years, respectively. The first
      biopsy sample contained internally placed nuclei in 7% of the muscle fibers,
      abundant minute myotubes, and hypertrophic muscle fibers. The second biopsy
      sample showed internally placed nuclei in 40% of the muscle fibers, and
      hypotrophic fibers. We suggest that the histological findings in early-onset CNM
      are the result of a complex dynamic process, which includes a delay in
      maturation.

PMID- 9600603
TI  - Does the observation of immunopositive cells after application of cell cycle
      markers always indicate that these cells proliferate?

PMID- 9600604
TI  - Prevalence of Salmonella in poultry carcasses and their products in Belgium.
AB  - During four subsequent years (1993 until 1996), a study was conducted to isolate
      and characterize Salmonella in poultry carcasses and their products sold in
      Belgium. This was a semiquantitative approach (absence per 100 cm2 or 25 cm2 or
      25 g and absence per cm2 or g) to elucidate the degree of Salmonella
      contamination of the poultry. Serotyping was performed during the last two and a
      half years. Samples were frozen and kept at -20 degrees C before analysis. This
      may have influenced the number of Salmonella recovered. No improvement in the
      rate of contamination was noted during these four years, with rates being 19.4%
      for 1993, 24.1% for 1994, 21.9% for 1995 and 36.7% for 1996. A 100% increase of
      Salmonella-positive samples resulted from cutting up the carcasses into
      individual parts. Chicken parts were more often contaminated with Salmonella than
      turkey parts. Boiling hen carcasses showed the highest Salmonella contamination.
      Prepared poultry, chicken parts and boiling hen carcasses are sometimes
      associated with Salmonella contamination levels of > 1 cfu/cm2 or g. In 1996,
      respectively 15.1%, 4.2% and 4.2% of highly contaminated samples (> 1 cfu/cm2 or
      g) were found for these product groups. The predominant three serotypes were S.
      enteritidis (16.3%), S. hadar (15.5%) and S. virchow (14.1%). S. newport was
      frequently isolated from turkey products.

PMID- 9600605
TI  - Biological control of major postharvest pathogens on apple with Candida sake.
AB  - Epiphytic microorganisms isolated from apples, pears and the surfaces of apple
      leaves were screened for antagonistic activity against Penicillium expansum (blue
      mold), Botrytis cinerea (gray-mold) and Rhizopus nigricans (Rhizopus rot) on
      apple (Malus domestica). A total of 933 bacteria and yeasts were tested in
      primary screening against P. expansum. Ninety-two strains reduced the lesion size
      on apples by more than 50%, 72 of which were isolated from the surface of apples.
      For secondary screening against P. expansum, B. cinerea and R. nigricans, 31
      strains were selected. The most promising isolate, CPA-1, was identified as
      Candida sake. This yeast, isolated from apples in storage season was very
      effective against all three diseases. Wounded Golden Delicious apples protected
      with the yeast suspension at a concentration of 2.6 x 10(6) CFU/ml and inoculated
      with conidia of B. cinerea and R. nigricans of 10(5) and 10(4) conidia/ml,
      respectively, did not develop rot. Complete control of P. expansum was obtained
      at the same concentration of the antagonist with a pathogen inoculum
      concentration of 10(3) conidia/ml. This strain, also provided excellent control
      of rot development under cold storage conditions. The strain of Candida sake can
      grow actively in aerobic conditions. In drop-inoculated wounds of apples, the
      populations of C. sake increased by more than 50-fold during the first 24 h at 20
      degrees C. The maximum population of C. sake on apple wounds was the same at 20
      as at 1 degrees C and was recovered after three and twenty days, respectively.

PMID- 9600606
TI  - Plantaricin LP84, a broad spectrum heat-stable bacteriocin of Lactobacillus
      plantarum NCIM 2084 produced in a simple glucose broth medium.
AB  - Lactobacillus plantarum NCIM 2084 produced an antibacterial substance when grown
      at 40 degrees C for 36 h in a laboratory medium. The antibacterial substance was
      active against a wide range of bacteria comprising Gram positive and negative
      foodborne pathogenic and spoilage bacteria. However, related mesophilic
      lactobacilli were not inhibited, except for L. amylovorus DSM 20531. The
      antimicrobial activity was observed between late log and stationary growth
      phases. The antibacterial substance was partially purified through concentration
      under vacuum, followed by extraction with methanol and acetone (M-A extract). On
      fractionation of the M-A extract through Sephadex G-25, the activity was present
      in an eluant volume of 85 to 100 ml (peak I), indicating an apparent molecular
      mass of between 1 and 5 kDa and the purification attained was 80-fold. The
      antimicrobial principle was stable to heat (121 degrees C for 20 min) and
      catalase, but sensitive to trypsin and chymotrypsin, indicating it to be a
      bacteriocin. The M-A extract exhibited a bactericidal and lytic effect against
      Bacillus cereus F 4810 and Escherichia coli D 21. The ability of L. plantarum
      NCIM 2084 to produce an effective bacteriocin in a simple growth medium is of
      potential interest in its application as a biopreservative in traditional
      fermented foods.

PMID- 9600607
TI  - Phage typing combined with pulsed-field gel electrophoresis and random amplified
      polymorphic DNA increases discrimination in the epidemiological analysis of
      Salmonella enteritidis strains.
AB  - Phage typing (PT) combined with pulsed-field gel electrophoresis (PFGE) and a
      random amplified polymorphic DNA (RAPD) fingerprinting method was used to
      characterize Salmonella enteritidis strains. Twenty-four epidemiologically
      unrelated isolates, sampled from diverse ecological niches and fifteen isolates
      from four well-defined outbreaks of foodborne gastroenteritis, were studied.
      Seven phage types, with a predominance of PT 4 (63% of isolates), were observed
      when analysing the epidemiologically unrelated group. PT 4 was detected in all of
      the ecological niches studied, including food and fecally polluted river and
      beach water. The discriminatory power for phage typing, the average probability
      that the typing system will assign a different type to two unrelated strains
      randomly sampled in the microbial population, was 0.62. Ten PFGE pattern types
      were obtained with Xba I restriction endonuclease enzyme among the unrelated
      isolates; thirteen isolates belonged to PFGE pattern type 1 and the rest of the
      PFGE types were assigned to one or two isolates. The Dice coefficient clustered
      the similarities of the PFGE patterns between 80-100%. PFGE showed a
      discriminatory power of 0.72. Five clearly distinct RAPD patterns were observed
      with the OPS-19 oligonucleotide, but the discrimination obtained was low (0.46).
      The combination of the three typing methods increased the number of types to
      seventeen, giving high discrimination (0.92). Seven of the isolates recovered
      from various ecological niches belonged to the combination PT 4/PFGE 1/RAPD A and
      other combinations were unique or included only two strains. The four
      epidemiologically well-defined foodborne outbreaks were associated with the PT 4
      phage type. In two of the outbreaks, other phage types (PT 7a and RDNC) were also
      observed in two isolates. Most of the isolates belonging to the foodborne
      outbreaks had an identical PFGE pattern (PFGE pattern type 1), but a difference
      in a restriction band was observed in an isolate belonging to an outbreak. Two
      RAPD patterns were observed in the outbreaks; RAPD pattern type A was detected in
      three of the four outbreaks. When the combined typing method was applied to the
      study, high concordance was observed and most of the outbreak strains belonged to
      the combination PT 4/PFGE 1/RAPD A. It is concluded that the combination of phage
      type with PFGE and RAPD provides a powerful discriminatory tool for the
      epidemiological analysis of unrelated and related strains of S. enteritidis.

PMID- 9600608
TI  - Synergistic effect of nisin and the lactoperoxidase system on Listeria
      monocytogenes in skim milk.
AB  - Nisin added at 10 or 100 IU/ml to ultra-high temperature processed (UHT) skim
      milk had no effect on counts of Listeria monocytogenes after 24 h at 30 degrees
      C, whereas addition of the lactoperoxidase system (LPS) resulted in counts of
      viable cells three log units lower than those of control milk after 24 h at 30
      degrees C. Addition of nisin and LPS showed a synergistic effect and resulted in
      counts up to 5.6 log units lower than the control milk. When the two
      preservatives were added to actively growing cells of L. monocytogenes in two
      steps with a 2 h interval, their synergistic effect was enhanced. Counts of L.
      monocytogenes Ohio after 24 h at 30 degrees C in milk with nisin and LPS added
      together after 3 h of growth were 5.7 log units lower than the control milk. The
      difference in counts increased to 7.4 log units if LPS was added after 3 h and
      nisin after 5 h of growth. Similar but less pronounced effects were observed for
      the more resistant strain L. monocytogenes Scott A.

PMID- 9600609
TI  - Improvement of garri quality by the inoculation of microorganisms into cassava
      mash.
AB  - Lactobacillus delbruckii, Lactobacillus coryneformis, and a Saccharomyces sp.,
      previously found among 214 isolates to be the highest producers of linamarase,
      amylase, and lysine were inoculated separately or mixed into cassava mash and
      fermented with, or without dewatering, for 24, 48, 72, 96 and 120 h. At the end
      of the fermentation period, the mash was converted to garri by heating over a gas
      burner. The mash and the garri resulting from it were assessed for lysine and
      residual cyanide, while the garri was also studied for its organoleptic
      properties. The inoculation of the microorganisms into cassava mash produced a
      sharp drop in the cyanide content of the mash, particularly when the mixture of
      organisms was inoculated into undewatered cassava mash rather the single
      organisms. After 24 h, while the cyanide content of the control (uninoculated
      mash) mash was 3.06 microg/g in the dewatered mash, and 4.24 microg/g in the
      undewatered mash, the inoculation of a mixture of the three organisms caused the
      cyanide content in the inoculated mashes to drop by 150% to 1.96 microg/g
      (dewatered mash) and by 300% to 1.43 microg/g (undewatered mash). It also appears
      that the process of producing the garri from the mash by heating, caused a
      further reduction of the cyanide content: thus the garri always contained less
      cyanide than the mash from which it was made. The lysine content of the mash was
      also highest when all three organisms were mixed; it also tended to increase with
      increasing length of fermentation of the mash. Whereas the single organism most
      effective in reducing the cyanide content of mash was Lactobacillus delbruckii,
      in the case of lysine production, it was the yeast. The organoleptic properties
      of the garri which were assessed were flavour, texture, colour and general
      acceptability. In general these properties were superior at the P < 0.01 level in
      garri made from the undewatered mash in comparison with that from dewatered mash,
      especially when the mixture of organisms was used. The inoculation of the mixture
      of the three organisms produced a dramatic reduction in the time (24 h) taken for
      the highest 'general acceptability' score to be given by the tasters when
      compared with the singly inoculated organisms and the control, which attained
      this characteristic after about 96 h of incubation in mash.

PMID- 9600610
TI  - Application of reverse transcriptase-nested-PCR for detection of poliovirus in
      mussels.
AB  - In order to identify polioviruses in molluscs, we hereby propose a method based
      on precipitation with PEG 6000 followed by the use of a commercial kit (RNAfast
      II-Molecular System-San Diego) for the extraction and purification of viral RNA.
      The RT-PCR phase is followed by a second amplification using nested primers to
      increase the sensitivity and specificity of the method. Tests were carried out on
      mollusc samples spiked with Poliovirus 1. Results showed that in samples
      subjected only to one round of PCR it was possible to detect Poliovirus
      concentrations as small as 10(3)TCID50/ml. The use of nested-PCR makes the system
      more sensitive and specific enabling the identification of Poliovirus
      concentrations as small as 1 TCID50/ml.

PMID- 9600611
TI  - An interlaboratory study to find an alternative to the MPN technique for
      enumerating Escherichia coli in shellfish.
AB  - Nine laboratories in eight countries tested 16 batches of common mussels (Mytilus
      edulis) over a 32 week period in order to find an alternative to the Most
      Probable Number (MPN) technique to enumerate E. coli. The alternatives
      investigated included the 3M Petrifilm system, the Merck Chromocult agar method
      and a Malthus conductance technique. The Petrifilm was found to be unsuitable and
      was subsequently dropped from the trial. After 669 analyses, a correlation of
      0.83 was observed for log E. coli counts between the MPN and Chromocult methods
      and there was no significant evidence that either method tended to give higher
      readings than the other. The MPN was slightly better than the Chromocult method
      for repeatability but the Chromocult was slightly better for reproducibility.
      However, the observed differences are probably too small to be of practical
      importance. On the basis of these data therefore, the two methods appear equally
      suitable for E. coli enumeration in shellfish. There were poor correlations
      between these methods and the Malthus technique. A small but significant number
      of samples tested positive on the Malthus instrument but were recorded negative
      on the MPN and Chromocult tests. Subsequent analysis positively identified E.
      coli from these Malthus assays. After statistical analysis, errors were noted in
      both the MPN and Chromocult methods but it was found that there would be no
      statistical differences if the Chromocult agar were used as an alternative to the
      MPN technique.

PMID- 9600612
TI  - The combined effect of nisin, leucocin F10, pH, NaCl and EDTA on the survival of
      Listeria monocytogenes in broth.
AB  - The combined effect of the bacteriocins nisin (1-2100 IU/ml) and leucocin F10 (1
      2100 AU/ml), pH (4.7-6.5), NaCl (0.7-4.5% w/l), ethylene diaminetetraacetic acid
      disodium salt (EDTA, 0.08-4.72 mmol/l) and inoculum level (10(3)-10(8) cfu/ml) on
      the survival of a pool of three strains of Listeria monocytogenes in broth was
      evaluated in three factorial experiments. Several factor combinations were found
      to prevent growth. Logistic regression analysis of the categorical data
      (survival/no survival) was used to generate predictive models for the probability
      of survival in 0.01 ml (P0.01) or 1 ml (P1). Predicted and observed probabilities
      of survival were not significantly different in 72% and 68.9% of treatments for
      P0.01 and P1, respectively. Unsafe predictions were obtained in 9.4% and 14.8% of
      treatments for P0.01 and P1, respectively. Nisin had a major effect on the
      probability of survival but the addition of leucocin F10 was necessary to prevent
      the survival of L. monocytogenes. Lower pH values significantly decreased the
      probability of survival, while NaCl and EDTA had only a minor effect. Doses of
      bacteriocins > 250 AU/ml, pH < 5.6 and EDTA > 0.2 mmol/l (0.074 g/l) were needed
      to reliably prevent survival of Listeria monocytogenes.

PMID- 9600613
TI  - Enhanced detection and enumeration of Listeria monocytogenes from foodstuffs and
      food-processing environments.
AB  - Listeria monocytogenes blood agar (LMBA) was compared to Listeria selective agar
      based on lithium chloride and ceftazidime (LA) and to the Oxford and Palcam media
      recommended by ISO and IDF for the detection and enumeration of L. monocytogenes
      from foodstuffs and food-processing environments. LMBA is based on trypticase soy
      agar with the following additions: sheep blood (5%) and as selective agents
      lithium chloride (10 g/l), polymyxin B sulphate (10 mg/l) and ceftazidime (20
      mg/l), whereas the selectivity of LA is based on lithium chloride (15 g/l) and
      ceftazidime (15 g/l). The media were compared in the detection of L.
      monocytogenes after enrichment from naturally contaminated foodstuffs (n = 423)
      and from food-processing environments (n = 93), and in the enumeration of the
      species from naturally contaminated foodstuffs (n = 287). LMBA was superior both
      to the standard media and to LA in detection after enrichment and also in
      enumeration, except in the case of fresh broiler cut samples. The overall
      sensitivities of the Palcam, Oxford, LA and LMBA media were 68%, 67%, 74% and 96%
      in detection after enrichment and 64%, 73%, 76% and 80% in the enumeration of the
      species from ready to eat foods. The superiority of LMBA is based on
      distinguishing L. monocytogenes from other Listeria species by detection of beta
      hemolysis, whereas the other media gave false-negative results because of the
      overgrowth of Listeria spp. other than L. monocytogenes, especially in detection
      after enrichment. A more selective medium than LMBA would have been required for
      the enumeration of the species from samples with high levels of competitive
      bacteria other than Listeria spp. The results indicate the need for a more
      specific isolation medium for L. monocytogenes in addition to those recommended
      by ISO and IDF for both detection and enumeration. LMBA offers an alternative to
      be used in combination with either Palcam or Oxford as well as with LA.

PMID- 9600614
TI  - Development of a growth medium suitable for exopolysaccharide production by
      Lactobacillus delbrueckii ssp. bulgaricus RR.
AB  - Complex media are commonly used in studies examining exopolysaccharide production
      by Lactobacillus delbrueckii ssp. bulgaricus. However, quantification of
      exopolysaccharide in complex medium can be complicated by interference due to
      carbohydrate polymers contained in media components. This study was undertaken to
      identify components of MRS, a common medium for cultivation of L. delbrueckii
      ssp. bulgaricus, that interfere with exopolysaccharide quantification, to develop
      a medium for production of exopolysaccharide that provides for growth of L.
      delbrueckii ssp. bulgaricus strain RR similar to MRS, and to demonstrate
      exopolysaccharide production by L. delbrueckii ssp. bulgaricus RR grown in the
      newly developed medium. Phenol-sulfuric acid determinations were conducted on
      uninoculated MRS broth with and without yeast extract, beef extract and proteose
      peptone #3. These three ingredients accounted for 94% of the total background
      exopolysaccharide-equivalent in MRS broth. Based on these results, a semi-defined
      medium (SDM) providing minimal interference was developed using yeast nitrogen
      base and Bacto casitone. Growth of L. delbrueckii ssp. bulgaricus RR at 42
      degrees C in semi-defined medium and MRS was evaluated, and generation times did
      not differ significantly (0.94 h in MRS and 0.85 h in SDM). Exopolysaccharide
      production by L. delbrueckii ssp. bulgaricus RR during growth in semi-defined
      medium was evaluated at 30 and 40 degrees C. The rate of exopolysaccharide
      production was lower at 30 degrees C (8.04 (mg/l-h) than at 40 degrees C (11.95
      (mg/l-h), but the maximal concentration of exopolysaccharide produced was similar
      at both temperatures.

PMID- 9600615
TI  - Characterisation and selection of probiotic lactobacilli for a preliminary
      minipig feeding trial and their effect on serum cholesterol levels, faeces pH and
      faeces moisture content.
AB  - Three out of 297 Lactobacillus strains isolated from pig faeces were selected for
      a feeding trial on account of their high bile-salt hydrolase (BSH) activity, bile
      salt resistance, low pH tolerance and the production of antimicrobial substances.
      Two strains were identified as Lactobacillus johnsonii and one as Lactobacillus
      reuteri by DNA-DNA hybridisation. L. johnsoniii BFE 1061 produced a bacteriocin
      active against a range of lactic acid bacteria (LAB) and nonrelated bacteria
      including Clostridium perfringens. Six minipigs were maintained on a high-fat,
      high-cholesterol ('Western Style') diet for 17 weeks after which the diet was
      supplemented with the 'probiotic mixture' containing the above mentioned three
      Lactobacillus strains at 2 x 10(12) CFU per pig per day for five weeks. The
      mixture was given as a resuspended lyophilisate. During a two week follow-up
      period the minipigs received only the 'Western-style' diet without probiotic
      supplementation. A lowering effect on serum cholesterol levels was indicated
      after three weeks probiotic feeding, concomitant with an increase in the moisture
      content of the faeces and Lactobacillus cell numbers. Triglycerides, pH and
      number of lactic acid bacteria in faeces were not significantly influenced by
      probiotic supplementation.

PMID- 9600616
TI  - Predicted and observed growth of Listeria monocytogenes in seafood challenge
      tests and in naturally contaminated cold-smoked salmon.
AB  - The performance of the Pathogen Modelling Program, the Food MicroModel, the
      Murphy-model and the Ross-model for growth of L. monocytogenes was evaluated by
      comparison with data from 100 seafood challenge tests and data from 13 storage
      trials with naturally contaminated sliced vacuum-packed cold-smoked salmon.
      Challenge tests with both cured and noncured products were studied, and graphs as
      well as the bias- and the accuracy factors were used for comparison of the
      observed and predicted growth. The Pathogen Modelling Program could not be
      successfully validated in seafood challenge tests. Growth rates were markedly
      overestimated and the mu(max)-bias factor was as high as 3.9 in challenge tests
      with cured products. On the basis of the effect of temperature, NaCl/a(w) and pH,
      the mu(max)-bias factor of the other three models studied, varied between 1.0 and
      2.3 in the challenge tests with cured and noncured seafoods. None of the models
      accurately predicted the growth in both cured and noncured seafoods. However, the
      results indicated that a new expanded model, including the additional effect of
      lactate and phenol, may provide accurate predictions of the growth of L.
      monocytogenes in challenge tests with various types of seafoods. Storage trials
      clearly showed the growth of L. monocytogenes in naturally contaminated cold
      smoked salmon to be markedly slower than growth in inoculated challenge tests.
      Consequently, all four models substantially overestimated growth in the naturally
      contaminated products. Temperature, pH, NaCl/a(w) and lactate were measured in
      the storage trials and on the basis of these parameters, the Food MicroModel
      mu(max)-bias factor was 5.2. Clearly, the model could not be successfully
      validated with naturally contaminated cold-smoked salmon. To improve the
      applicability of predictive models to fish products, it is suggested to include
      studies with naturally contaminated products in the development and validation of
      models with seafood pathogens.

PMID- 9600617
TI  - Behavior of Salmonella typhimurium DT104 during the manufacture and storage of
      pepperoni.
AB  - Pepperoni batter (ca. 70% pork:30% beef) was prepared and subsequently inoculated
      with a six-strain cocktail (ca. 4.4 x 10(7) per gram batter) of Salmonella
      typhimurium DT104. After fermentation at 36 degrees C and 92% relative humidity
      (RH) to < or = pH 4.8, counts of the pathogen decreased by about 1.3 log10 units.
      An additional 1.6 log10 unit decrease was observed following drying at 13 degrees
      C and 65% RH to a moisture protein ratio (M/Pr) of 1.6:1. After storage of
      pepperoni sticks for 56 days under vacuum at 4 or 21 degrees C, counts of the
      pathogen were about 4.6 and 6.6 log10 units lower, respectively, compared with
      starting levels in the batter. These data establish that fermentation and drying
      result in about a 3.0 log10 reduction in numbers of S typhimurium DT104 in
      pepperoni sticks and that storage of pepperoni sticks under vacuum at ambient
      temperature is more severe on the pathogen than refrigerated storage.

PMID- 9600618
TI  - Protection of young chicks against Salmonella kedougou by administration of
      intestinal microflora.
AB  - One-day old chickens were treated with a faecal suspension and faecal samples
      were cultivated either in non-selective broth (Viande Levure broth) or in broths
      selective for Lactobacillus spp., Bacteroides spp., faecal enterococci and
      coliforms. The chickens were infected 48 h later with 10(4) colony-forming units
      of nalidixic-acid resistant Salmonella kedougou and examined seven days later.
      Faecal suspensions and faecal samples cultivated in non-selective broth exerted a
      protection against Salmonella infection; no protection was obtained with faecal
      samples cultivated in selective broths, administered either alone or in
      combination.

PMID- 9600619
TI  - Effect of gamma irradiation on the production of cell wall degrading enzymes by
      Aspergillus niger.
AB  - Fungi occurring in Egyptian fruits in the City of Qena were studied. Results from
      the examination of 25 replicated samples of plums, pears and apples are reported.
      Examinations were carried out by direct plating after surface disinfection in a
      0.5% (w/v) calcium hypochlorite solution on Czapek's-Dox agar. The dominant
      fungus found in the three types of fruit was Aspergillus niger, which was present
      in 88% of plum samples, 80% of pear samples and all of the apple samples. The
      lowest dose of gamma irradiation (1 MCi for 10 min) enhanced the three isolates
      of A. niger investigated to produce more biomass and polygalactronase,
      pectinmethylglacturonase, cellulase and protease. The higher doses (1 MCi for 20
      and 30 min) were inhibitory to the growth of A. niger.

PMID- 9600620
TI  - Production of bacteriocin-like-substance by Listeria innocua against Listeria
      monocytogenes.
AB  - Cultures and culture filtrates of 129 Listeria innocua strains were examined for
      inhibitory activity against 18 strains of Listeria monocytogenes. Of the strains
      examined, 114 (88.4%) cultures and 126 (97.7%) culture filtrates had an
      inhibitory activity against strains of L. monocytogenes and most filtrates were
      sensitive to trypsin treatment. The authors concluded that most L. innocua
      strains produce a trypsin sensitive bacteriocin-like substance against L.
      monocytogenes.

PMID- 9600621
TI  - Is interferon-alpha a neuromodulator?
AB  - Interferons were initially characterized for their ability to 'interfere' with
      viral replication, slow cell proliferation, and profoundly alter immunity. They
      are a group of hormone-like molecules synthesized and secreted by macrophages,
      monocytes, T lymphocytes, glia, and neurons. These cytokines have been shown to
      have several regulatory roles and diverse biological activities, including
      control of cellular and humoral immune responses, inflammation, and tumor
      regression. In addition, there are many reports indicating that interferon-alpha
      (IFN-alpha) participates in the regulation of various cellular and humoral
      processes such as the endocrine system modulates behavior, brain activity,
      temperature, glucose sensitive neurons, feeding pattern and opiate activity.
      Therefore, IFN-alpha can be considered as a physiological modulator, with only
      one of its functions being the ability to hinder viral replication
      intracellularly.

PMID- 9600622
TI  - Sodium channels as molecular targets for antiepileptic drugs.
AB  - Voltage-gated sodium channels mediate regenerative inward currents that are
      responsible for the initial depolarization of action potentials in brain neurons.
      Many of the most widely used antiepileptic drugs, as well as a number of
      promising new compounds suppress the abnormal neuronal excitability associated
      with seizures by means of complex voltage- and frequency-dependent inhibition of
      ionic currents through sodium channels. Over the past decade, advances in
      molecular biology have led to important new insights into the molecular structure
      of the sodium channel and have shed light on the relationship between channel
      structure and channel function. In this review, we examine how our current
      knowledge of sodium channel structure-function relationships contributes to our
      understanding of the action of anticonvulsant sodium channel blockers.

PMID- 9600623
TI  - Understanding glial abnormalities associated with myelin deficiency in the jimpy
      mutant mouse.
AB  - Jimpy is a shortened life-span murine mutant showing recessive sex-linked
      inheritance. The genetic defect consists of a point mutation in the PLP gene and
      produces a severe CNS myelin deficiency that is associated with a variety of
      complex abnormalities affecting all glial populations. The myelin deficiency is
      primarily due to a failure to produce the normal amount of myelin during
      development. However, myelin destruction and oligodendrocyte death also account
      for the drastic myelin deficit observed in jimpy. The oligodendroglial cell line
      shows complex abnormalities in its differentiation pattern, including the
      degeneration of oligodendrocytes through an apoptotic mechanism. Oligodendrocytes
      seem to be the most likely candidate to be primarily altered in a disorder
      affecting myelination, but disturbances affecting astrocytes and microglia are
      also remarkable and may have a crucial significance in the development of the
      jimpy disorder. In fact, the jimpy phenotype may not be attributed to a defect in
      a single cell but rather to a deficiency in the normal relations between glial
      cells. Evidences from a variety of sources indicate that the jimpy mutant could
      be a model for disturbed glial development in the CNS. The accurate knowledge of
      the significance of PLP and its regulation during development must be of vital
      importance in order to understand glial abnormalities in jimpy.

PMID- 9600624
TI  - Manipulation of gene expression in the mammalian nervous system: application in
      the study of neurite outgrowth and neuroregeneration-related proteins.
AB  - A fundamental issue in neurobiology entails the study of the formation of
      neuronal connections and their potential to regenerate following injury. In
      recent years, an expanding number of gene families has been identified involved
      in different aspects of neurite outgrowth and regeneration. These include
      neurotrophic factors, cell-adhesion molecules, growth-associated proteins,
      cytoskeletal proteins and chemorepulsive proteins. Genetic manipulation
      technology (transgenic mice, knockout mice, viral vectors and antisense
      oligonucleotides) has been instrumental in defining the function of these neurite
      outgrowth-related proteins. The aim of this paper is to provide an overview of
      the above-mentioned four approaches to manipulate gene expression in vivo and to
      discuss the progress that has been made using this technology in helping to
      understand the molecular mechanisms that regulate neurite outgrowth. We will show
      that work with transgenic mice and knockout mice has contributed significantly to
      the dissection of the function of several proteins with a key role in neurite
      outgrowth and neuronal survival. Recently developed viral vectors for gene
      transfer in postmitotic neurons have opened up new avenues to analyze the
      function of a protein following local expression in naive adult rodents. The
      initial results with viral vector-based gene transfer provide a conceptual
      framework for further studies on genetic therapy of neuroregeneration and
      neurodegenerative diseases.

PMID- 9600625
TI  - Role of mitochondrial Ca2+ regulation in neuronal and glial cell signalling.
AB  - It is becoming increasingly clear that mitochondrial Ca2+ uptake from and release
      into the cytosol has important consequences for neuronal and glial activity. Ca2+
      regulates mitochondrial metabolism, and mitochondrial Ca2+ uptake and release
      modulate physiological and pathophysiological cytosolic responses. In glial
      cells, inositol 1,4,5-trisphosphate-dependent Ca2+ responses are faithfully
      translated into elevations in mitochondrial Ca2+ levels, which modifies cytosolic
      Ca2+ wave propagation and may activate mitochondrial enzymes. The location of
      mitochondria within neurones may partially determine their role in Ca2+
      signalling. Neuronal death due to NMDA-evoked Ca2+ entry can be delayed by an
      inhibitor of the mitochondrial permeability transition pore, and mitochondrial
      dysfunction is being increasingly implicated in a number of neurodegenerative
      conditions. These findings are illustrative of an emerging realization by
      neuroscientists of the importance of mitochondrial Ca2+ regulation as a modulator
      of cellular energetics, endoplasmic reticulum Ca2+ release and neurotoxicity.

PMID- 9600626
TI  - Diurnal differences in rat's motor response to amphetamine.
AB  - The dose-response characteristics and time-course of amphetamine's effect on
      motor activity after a single injection given to rats at four different times of
      the light/dark cycle was investigated using a computerized infrared motor
      activity recording system. After 7 days of acclimation and 2 days of baseline
      activity recording, rats received a single subcutaneous injection of vehicle
      (saline) or 0.6, 1.25 or 10 mg/kg amphetamine at 08.00, 14.00, 20.00 or 02.00.
      Recording was then resumed for an additional 36 to 48 h. The locomotor indices
      analyzed were horizontal activity, total distance, vertical activity, stereotypic
      activity and number of stereotypic movements. All doses (0.6. 1.25 and 10 mg/kg)
      significantly elevated (P < 0.01) locomotor activity compared to baseline at all
      times of administration. At all injection times, the maximum increase over
      baseline generally occurred following the 1.25 mg/kg dose of amphetamine (P <
      0.001). The effect of the lower doses (0.6 and 1.25 mg/kg) on forward locomotion
      remained the same throughout the light/dark cycle regardless of the large
      difference in baseline motor activity between the light and dark phases. However,
      the effects of 10 mg/kg amphetamine on general stereotypic behavior, as well as
      the ability to cause subsequent depression of nocturnal forward ambulation, were
      dependent on the time of drug administration. These results showed that the
      circadian rhythms of locomotor and stereotypic effects of amphetamine are
      different.

PMID- 9600627
TI  - The dopamine D4 receptor antagonist L-745,870: effects in rats discriminating
      cocaine from saline.
AB  - The contribution of dopamine D4 receptors to the discriminative stimulus effects
      of cocaine was evaluated by testing the selective dopamine D4 receptor
      antagonist, L-745,870 (3-([4-(4-chlororphenyl) piperazin-1-yl] methyl)-1 H
      pyrrolo[2,3-b] pyridine), alone and in combination with cocaine, in rats trained
      to discriminate cocaine (10 mg/kg) from saline. The antagonist (1-10 mg/kg)
      failed to engender cocaine-appropriate responding when injected alone, and failed
      to modify the cocaine dose-response curve when injected as a pre-treatment;
      however, it reduced response rates dose-dependently. Conversely, the dopamine 'D1
      like' receptor antagonist, SCH 39166 ((-)-trans-6,7,7a,8,9, 13b-hexahydro-3
      chloro-2hydroxy-N-methyl-5H-benzo[d]napth o-?2,1-b?azepine, produced surmountable
      antagonism. Results suggest that dopamine D4 receptors play a negligible role in
      cocaine's discriminative stimulus effects, and further support a critical
      involvement of dopamine D1-like receptors.

PMID- 9600628
TI  - Antidepressant-like effects of alnespirone (S 20499) in the learned helplessness
      test in rats.
AB  - The effects of the new chroman derivative, alnespirone (S 20499), which is a
      selective 5-HT1A receptor agonist, were investigated in an animal model of
      depression, the learned helplessness test. Rats previously submitted to a session
      of 60 inescapable electric foot shocks (learned helpless controls) exhibited a
      deficit in escape performance in three subsequent shuttle-box sessions.
      Alnespirone was administered twice daily via the oral route (2.5, 5, 10, 20 mg
      kg(-1) day(-1)). It was shown to protect against the elevation in escape failures
      caused by exposure to the uncontrollable aversive situation at 5 and 10 mg kg(-1)
      day(-1) p.o. (13+/-2 and 10+/-3 escape failures, respectively, vs. 9+/-2 escape
      failures in control rats). In addition, alnespirone had a tendency to elevate the
      number of intertrial crossings during the resting periods, depending on the dose
      and day on which the avoidance task was performed (15+/-2 intertrial crossings at
      the dose of 5 mg kg(-1) day(-1), vs. 5+/-2 intertrial crossings for the helpless
      control rats, on the second day). In comparison, imipramine (64 mg kg(-1) day(-1)
      p.o.) provided marked protection on all three days of the avoidance task and
      tended to increase the number of intertrial crossings during the resting periods
      on the second and the third days. It is concluded that alnespirone exerts
      antidepressant-like properties in the learned helplessness test in rats, in a
      manner similar to 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), buspirone
      and ipsapirone, other 5-HT1A receptor agonists.

PMID- 9600629
TI  - The effects of beta-carbolines in rats trained with ibogaine as a discriminative
      stimulus.
AB  - The structural features and hallucinogenic properties shared by ibogaine and
      certain beta-carbolines prompted the evaluation of several representative beta
      carbolines in rats trained with ibogaine as a discriminative stimulus. In a
      previous report from our laboratory harmaline completely substituted for ibogaine
      (83.5%). In the present study, only 6-methoxyharmalan completely substituted
      (86.3%). However, partial substitution was observed with harmine, harmane,
      harmalol, and tetrahydro-beta-carboline (THBC). Norharmane and 6,7-dimethoxy-4
      ethyl-carboline-3-carboxylate (DMCM) failed to produce appreciable substitution.
      These results provide evidence for an ibogaine-like ether this extends to the
      previously reported anti-addictive effects of ibogaine remains to be established.

PMID- 9600630
TI  - Antihyperalgesic effects of spinal cannabinoids.
AB  - Cannabinoids have been widely reported to produce antinociception in models such
      as tail flick and hot plate. However, their role in modulating thermal
      hyperalgesia is unknown. The potency of some drugs, such as the opioids,
      increases during hyperalgesia. Thus, we evaluated whether there is a change in
      the effectiveness of intrathecal cannabinoids with hyperalgesia. Additionally, we
      evaluated whether cannabinoids could inhibit capsaicin-evoked neurosecretion from
      isolated rat spinal cord. Our results indicate that 1 fmol anandamide (i.t.)
      completely blocked carrageenan-induced thermal hyperalgesia. However, anandamide
      at doses as high as 100 pmol had no effect on thermal latencies in normal
      animals. Additionally, anandamide inhibited K+- as well as capsaicin-evoked
      immunoreactive calcitonin gene-related peptide release. Finally, cannabinoid
      receptors were identified in sensory neurons. Collectively, these results
      indicate that there is an increased effectiveness of modulation of thermal
      nociceptive thresholds by spinal cannabinoids during hyperalgesia. This
      antihyperalgesic effect may be the result of cannabinoid-induced inhibition of
      neurosecretion from certain primary afferent fibers.

PMID- 9600631
TI  - Responses to neuropeptide Y in adult hamster suprachiasmatic nucleus neurones in
      vitro.
AB  - We investigated the effects of neuropeptide Y and related analogues on the
      extracellularly recorded spontaneous firing rate activity of adult Syrian hamster
      suprachiasmatic nucleus neurones in vitro. Sixty-seven neurones were tested with
      neuropeptide Y: 45% were suppressed, 4% were activated, and the remaining 51%
      were unresponsive. These responses were not blocked by the GABA receptor
      antagonist bicuculline, indicating that neuropeptide Y-evoked responses did not
      appear to be dependent on GABA(A) receptor activation. We tested the effects of
      the neuropeptide Y Y1 receptor agonist [Leu31, Pro34]neuropeptide Y and the
      neuropeptide Y Y2 receptor agonist neuropeptide Y-(13-36) on nine cells
      suppressed by neuropeptide Y in order to determine the receptor subtype(s)
      mediating the effects of neuropeptide Y. Four of nine cells were suppressed by
      [Leu31, Pro34]neuropeptide Y only, one of nine was suppressed by neuropeptide Y
      (13-36) only, two of nine were suppressed by both compounds, while the remaining
      two cells did not respond to either compound. These data suggest that
      neuropeptide Y can modulate suprachiasmatic nucleus function directly, without
      recruitment of GABA(A) interneurones. Further, our results indicate that
      neuropeptide Y may act on more than one receptor subtype within the adult hamster
      suprachiasmatic nucleus.

PMID- 9600632
TI  - Preferential blockade of cholecystokinin-8S-induced increases in aspartate and
      glutamate levels by the CCK(B) receptor antagonist, L-365,260, in rat brain.
AB  - In the present studies, the ability of a locally delivered cholecystokinin (CCK)
      receptor agonist and systemically delivered antagonists to modulate extracellular
      levels of aspartate and glutamate in the frontal cortex of anaesthetised rats and
      frontal cortex and caudate-putamen of freely moving rats was investigated using
      an in vivo microdialysis technique. In the anaesthetised rats, local application
      of sulphated CCK octapeptide (CCK-8S, 10 microM) into the frontal cortex enhanced
      extracellular aspartate levels to a maximum of 265+/-16% of the basal levels,
      whereas glutamate levels were increased to a maximum of 168+/-7% of the basal
      levels. Given 40 min prior to the cortical perfusion of 10 microM of CCK-8S, the
      CCK(B) receptor antagonist, L-365,260 (20 mg/kg, s.c.), limited the rise in
      cortical aspartate by over half to 170+/-10% of the basal levels. However, this
      same dose of L-365,260 still allowed CCK-8S to increase glutamate by 44+/-15%
      above the basal levels. Whereas the enhanced glutamate levels were totally
      unaffected by systemic administration of the CCK(A) receptor antagonist, L
      364,718 (20 mg/kg, -40 min, s.c.), this treatment was able to limit the elevation
      in aspartate to 220+/-4% of the basal levels. In the freely moving rats, local
      perfusion of CCK-8S (10 microM) increased aspartate and glutamate levels to
      maxima of 275+/-12% and 225+/-14% of the basal levels, respectively, in the
      frontal cortex. In the caudate-putamen, aspartate and glutamate levels were also
      elevated by CCK-8S (10 microM) to 248+/-15% and 185+/-12% of the basal levels,
      respectively. The respective increase in aspartate and glutamate induced by CCK
      8S (10 microM) were limited to 140+/-10% and 124+/-6% (frontal cortex), of the
      basal levels, and 162+/-15% and 143+/-8% (caudate-putamen), by 40 min
      pretreatment with L-365,260 (20 mg/kg, s.c.). In conclusion, CCK-8S was able to
      enhance both aspartate and glutamate overflow in the frontal cortex of
      anaesthetised rats, and frontal cortex and caudate-putamen of freely moving rats.
      These increases were preferentially offset by the selective CCK(B) receptor
      antagonist, L-365,260, since no influence could be discerned using the selective
      CCK(A) receptor antagonist, L-364,718.

PMID- 9600633
TI  - Intraventricular insulin reduces the antinociceptive effect of [D-Ala2, NMePhe4,
      Gly-ol5]enkephalin in mice.
AB  - The effects of pretreatment with insulin on the antinociception induced by
      intracerebroventricular (i.c.v.) administration of the mu-opioid receptor agonist
      [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAMGO) were studied in mice.
      Intracerebroventricular pretreatment with insulin (1 and 3 mU) for 60 min dose
      dependently attenuated the antinociception induced by i.c.v. DAMGO (5.6 ng) in
      mice. Intracerebroventricular pretreatment with a highly selective tyrosine
      kinase inhibitor, lavendustin A, at doses of 100 and 300 ng for 10 min, dose
      dependently reversed the antinociceptive effect of DAMGO (5.6 ng) in insulin
      treated mice. The antinociceptive effect of DAMGO (5.6 ng, i.c.v.) was
      significantly reduced in C57BL/KsJ-db/db diabetic mice compared with that in age
      matched control (C57BL/KsJ-db/ + + ) mice. When C57BL/KsJ-db/db diabetic mice
      were pretreated with lavendustin A (300 ng), the antinociceptive effect of DAMGO
      was significantly increased. These results indicate that tyrosine kinase may be
      involved in the reduction of DAMGO-induced antinociception by insulin in mice.
      Furthermore, the attenuation of DAMGO-induced antinociception in C57BL/KsJ-db/db
      diabetic mice may be due in part to increased tyrosine kinase activity as a
      result of hyperinsulinemia.

PMID- 9600634
TI  - Maternal cocaine exposure alters mesolimbic dopaminergic function in rat
      offspring.
AB  - Hooded Lister female rats were treated with either saline or cocaine (20 mg/kg
      s.c.) from gestational day 10 every other day until weaning (postnatal day 25).
      In vivo microdialysis has shown that maternal cocaine exposure significantly
      decreases basal extracellular concentrations of dopamine in the nucleus accumbens
      of young-adult offspring (4 weeks after cessation of cocaine treatment).
      Moreover, the increase in extracellular dopamine levels induced by a challenge
      dose of K+ (intracerebral 60 mM K+ artificial cerebrospinal fluid (aCSF)
      infusion) or cocaine (15 mg/kg i.p.) was significantly attenuated in rats exposed
      to cocaine during perinatal life with respect to controls. The alterations in
      mesolimbic dopamine transmission observed in these experiments might underlie
      behavioral abnormalities induced in rat offspring by maternal exposure to cocaine
      at dose levels which do not produce gross malformations and/or overt neurotoxic
      effects.

PMID- 9600635
TI  - Nerve growth factor improves evoked potentials and long-term potentiation in the
      dentate gyrus of presenile rats.
AB  - Chronic infusion of nerve growth factor (NGF, 1.2 microg/day) for 14 days to
      presenile rats (17 months at the beginning of treatment) that showed an initial
      cognitive impairment led to an improved long-term potentiation in the dentate
      gyrus. Both the relative increase of the slope of the population excitatory
      postsynaptic potential and that of the population spike were enhanced by NGF
      pretreatment after long-term potentiation induction at 400 Hz. The treatment was
      also able to increase the diminished baseline amplitude of the population spike,
      an effect not seen when the treatment was applied to older animals [Bergado, J.,
      Fernandez, C.I., Gomez-Soria, A., Gonzalez, O., 1997a. Chronic intraventricular
      infusion with NGF improves LTP in old cognitively-impaired rats. Brain Res. 770,
      1-9] stressing the importance of an early start of trophic therapy to achieve
      better results.

PMID- 9600636
TI  - Evaluation of a GPIIb/IIIa antagonist YM337 in a primate model of middle cerebral
      artery thrombosis.
AB  - We compared the antithrombotic effect of anti-GPIIb/IIIa antibody Fab fragment
      YM337 with that of a thromboxane A2 synthetase inhibitor, sodium ozagrel. With
      the monkeys under halothane anesthesia, the right middle cerebral artery was
      observed via a transorbital approach without cutting the dura mater.
      Photoillumination (wavelength 540 nm) was applied to the middle cerebral artery,
      and then rose bengal (20 mg kg(-1)) was administered intravenously. The
      experimental drugs were intravenously injected 15 min before rose bengal
      injection and followed by continuous infusion for 3 h after dye injection. The
      thrombotic occlusion induced by this photochemical reaction in monkey middle
      cerebral artery was reproducible. YM337 significantly prolonged the time to first
      occlusion and the total time of arterial patency during the 3-h observation
      period after dye injection. In contrast, sodium ozagrel had no significant
      effect. YM337 but not sodium ozagrel significantly inhibited ex vivo ADP-induced
      platelet aggregation. However, while sodium ozagrel significantly inhibited the
      thromboxane B2 generation accompanying arachidonic acid-induced platelet
      aggregation, YM337 had no effect on this variable. Neurological deficit in the
      YM337-treated animals was significantly milder than that in the control group.
      The area of infarct in the YM337 treatment animals was smaller than that in the
      control group. The novel selective GPIIb/IIIa antagonist YM337 was effective in
      ameliorating the decrease in patency of the middle cerebral artery and reducing
      the area of cerebral infarction in monkeys.

PMID- 9600637
TI  - Ecabet sodium, a locally acting antiulcer drug, inhibits urease activity of
      Helicobacter pylori.
AB  - In order to clarify the mechanism of the anti-Helicobacter pylori action of
      ecabet sodium (ecabet), a locally acting antiulcer drug, we evaluated the effects
      of ecabet on H. pylori urease activity in vitro. H. pylori was cultured and a
      crude preparation of urease was made. Urea-dependent survival of H. pylori at
      acid pH was significantly inhibited by ecabet. The urease activity of intact
      cells and a crude enzyme preparation from H. pylori had two pH optima: pH 4.5-5.0
      and 8.0. Ecabet (1-4 mg/ml) concentration dependently inhibited the urease
      activity of both preparations at pH 5.0, but there was no inhibition at pH 8.0.
      The enzyme activity was inhibited by ecabet gradually and was not restored by
      dilution, in contrast to the inhibition elicited by benzohydroxamic acid, a
      specific and reversible urease inhibitor. These results suggest that irreversible
      inhibition of H. pylori urease activity contributes to the anti-H. pylori action
      of ecabet.

PMID- 9600638
TI  - Analysis of the expression of intercellular adhesion molecule-1 in cells of the
      human bronchial epithelial cell line NCI-H292.
AB  - The mechanism of the expression of intercellular adhesion molecule-1 (ICAM-1) on
      epithelial cells was analyzed using NCI-H292 cells, a human bronchial epithelial
      cell line. Treatment with interferon-gamma (100 U/ml) or the protein kinase C
      activator 12-O-tetradecanoylphorbol 13-acetate (TPA) (16.2 nM) induced ICAM-1
      expression. The interferon-gamma-induced ICAM-1 expression was reduced by the
      tyrosine kinase inhibitor genistein (4',5,7-trihydroxyisoflavone) (37 to 185
      microM), but not by the protein kinase C inhibitor Ro 31-8425 ((3-[8
      (aminomethyl)-6,7,8,9-tetrahydropyrido [1.2-a]indol-10-yl]-4-(1-methyl-1 H
      pyrrole-2,3-dione) (10 microM). The TPA-induced ICAM-1 expression was reduced by
      the protein kinase C inhibitor Ro 31-8425 (1 to 10 microM), but not by the
      tyrosine kinase inhibitor genistein (185 microM). The protein kinase A inhibitor
      H-89 (N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide) did not
      affect the ICAM-1 expression induced by interferon-gamma or TPA. Pyrrolidine
      dithiocarbamate (1-pyrrolidinecarbodithioic acid) (100 microM), an inhibitor of
      nuclear factor kappaB (NF-kappaB) activation. enhanced the ICAM-1 expression
      induced by interferon-y, but reduced that induced by TPA. The changes in ICAM-1
      expression on the cell surface were correlated with the changes in ICAM-1 mRNA
      levels. Combined treatment with interferon-gamma and TPA induced more than
      additive ICAM-1 expression. These findings suggest that interferon-gamma induces
      ICAM-1 expression by a tyrosine kinase-dependent mechanism, but that TPA induces
      it by a protein kinase C- and NF-kappaB-dependent mechanism.

PMID- 9600639
TI  - Inhibition of striatal dopamine transporter activity by 17beta-estradiol.
AB  - Striatal synaptosomes from ovariectomized rats were prepared to examine the
      effect of 17beta-estradiol on [3H]dopamine uptake. Estradiol inhibited
      [3H]dopamine uptake in a dose-dependent manner, with an IC50 of 7.2 microM. Use
      of identical concentrations of progesterone had no effect on [3H]dopamine uptake.
      The effects of estradiol were exerted by decreasing the affinity of the
      transporter for dopamine, as revealed by a dose-dependent increase in the Km. The
      Km values for 0 (control), 10, and 100 microM estradiol were 108+/-11 258+/-44
      and 415+/-40 nM, respectively, with each of the three concentrations tested being
      significantly different among each other. No statistically significant
      differences were obtained for the Vmax, with values for the three increasing
      doses being 9.2+/-0.8, 8.3+/-0.5 and 7.3+/-0.8 pmol/min per mg protein. These
      results demonstrate that estradiol, but not progesterone, inhibits striatal
      dopamine uptake by decreasing the affinity of the transporter for dopamine. Such
      a mechanism may serve as one of the bases for the modulatory effects of estradiol
      upon the nigrostriatal dopaminergic system.

PMID- 9600640
TI  - Tolerance development to antimitogenic actions of prostacyclin but not of
      prostaglandin E1 in coronary artery smooth muscle cells.
AB  - This study compares the antimitogenic effects of iloprost and prostaglandin E1 on
      platelet-derived growth factor-BB stimulated DNA synthesis ([3H]thymidine
      incorporation) in bovine coronary artery smooth muscle cells. When added 20-24 h
      after stimulation with platelet-derived growth factor-BB (20 ng/ml), both
      iloprost and prostaglandin E1, concentration-dependently (IC50 3-5 nM) inhibited
      DNA synthesis. However, when added together with the growth factor (0-24 h), the
      inhibition of DNA synthesis by iloprost was markedly attenuated, indicating
      tolerance development. In contrast, no tolerance to antimitogenic effects of
      prostaglandin E1 or forskolin were observed. When added to iloprost-tolerant
      cells, both prostaglandin E1 and forskolin, still inhibited DNA synthesis. There
      was no evidence for transcriptional down-regulation of prostacyclin receptor gene
      by iloprost. The data demonstrate a tolerance development to antimitogenic
      actions of prostacyclin but not of prostaglandin E1 and suggest that the
      receptors, mediating the antiproliferative actions of these prostaglandins, may
      be different.

PMID- 9600641
TI  - Adaptations to chronic agonist exposure of mu-opioid receptor-expressing Chinese
      hamster ovary cells.
AB  - To investigate cellular adaptation responses induced by chronic agonist treatment
      of the mu-opioid receptor, Chinese hamster ovary (CHO) cells were stably
      transfected with the rat mu-opioid receptor cDNA. Chronic treatment with agonists
      selective for the mu-opioid receptor, [D-Ala2, N-MePhe4, Gy-ol5]enkephalin
      (DAMGO), morphine and fentanyl, time- and dose-dependently induced down
      regulation of the mu-opioid receptor. The down-regulation was not significantly
      affected by pretreatment with pertussis toxin, but was completely blocked by
      treatment with hypertonic sucrose, suggesting that receptor internalization
      mediated by clathrin-coated vesicles is an essential step in the mu-opioid
      receptor down-regulation. On the other hand, forskolin-stimulated cyclic AMP
      formation was increased by chronic DAMGO treatment, which was inhibited by
      pertussis toxin pretreatment. These results indicate that two adaptation
      responses induced by chronic agonist treatment of the mu-opioid receptor
      expressing CHO cells, down-regulation of the mu-opioid receptor and
      supersensitization of adenylate cyclase, are mediated by distinct mechanisms.

PMID- 9600642
TI  - [125I]endothelin-1 binding to renal brush border and basolateral membranes.
AB  - [125I]Endothelin-1 bound with high affinity to a single site on both brush border
      membranes (Kd=192+/-26 pM. Bmax=314+/-49 fmol/mg) and basolateral membranes
      (Kd=94.7+/-3.4 pM, Bmax=612+/-107 fmol/mg) isolated from rat renal cortex.
      Competition binding experiments using subtype selective ligands revealed that the
      proportion of ET(B) to ET(A) receptors was 80:20 and 60:40 in the brush border
      membrane and the basolateral membrane, respectively. The results demonstrate that
      endothelin-1 binds to brush border membranes, and that endothelin ET(B) receptors
      may be involved in the previously described effects of endothelin-1 on brush
      border membrane Na+ transport.

PMID- 9600643
TI  - Nitric oxide mediates mecamylamine- and naloxone-precipitated nicotine
      withdrawal.
AB  - A nitric oxide synthase inhibitor blocked nicotine abstinence signs and increased
      weight loss in male, nicotine-dependent rats during withdrawal precipitated by
      the nicotinic receptor antagonist mecamylamine or the opioid receptor antagonist
      naloxone. These results indicate that nitric oxide systems mediate important
      aspects of the expression of nicotine physical dependence and suggest the
      potential use of nitric oxide synthase inhibitors as aids in tobacco smoking
      cessation.

PMID- 9600644
TI  - Evaluation of PD 154075, a tachykinin NK1 receptor antagonist, in a rat model of
      postoperative pain.
AB  - PD 154075 ([(2-benzofuran)-CH2OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH3) Ph) is a
      selective tachykinin NK1 receptor antagonist. Its effect on development and
      maintenance of thermal and mechanical hypersensitivity was examined in a rat
      model of surgical pain. When administered 30 min before surgery, PD 154075 dose
      dependently (3-100 mg/kg, s.c.) prevented the development of thermal and
      mechanical hypersensitivity with respective minimum effective doses of 10 and 30
      mg/kg. These antihypersensitivity effects lasted for 72 h. In contrast, the
      administration of PD 154075 (30 mg/kg, s.c.) after surgery had little or no
      effect on these nociceptive responses. PD 154075 antagonised thermal
      hypersensitivity induced by intrathecal administration of substance P, over the
      same dose range that blocked surgical hypersensitivity. However, it only
      partially blocked the thermal hypersensitivity induced by the selective NK2
      receptor agonist [betaAla8]neurokinin A-(4-10). Morphine dose-dependently (1-6
      mg/kg, s.c.) lengthened isoflurane and pentobarbitone-induced sleeping time in
      the rat. In contrast, PD 154075 (3-100 mg/kg, s.c.) did not interact with these
      anaesthetics. It is suggested that tachykinin NK1 receptor antagonists, such as
      PD 154075, may possess therapeutic potential as pre-emptive antihypersensitive
      agents.

PMID- 9600645
TI  - Co-administration of adenosine kinase and deaminase inhibitors produces supra
      additive potentiation of N-methyl-D-aspartate-evoked adenosine formation in
      cortex.
AB  - Activation of glutamate receptors triggers the release of adenosine, which exerts
      important inhibitory actions in the brain. Evoked adenosine release is
      potentiated when either adenosine kinase or adenosine deaminase are inhibited. We
      studied the effects of concurrent inhibition of adenosine kinase and adenosine
      deaminase on N-methyl-D-aspartate (NMDA)-evoked formation of extracellular
      adenosine in slices of rat parietal cortex, to determine if combinations of
      inhibitors of adenosine kinase and adenosine deaminase can produce supra-additive
      potentiation of this adenosine formation. Combinations of low concentrations of
      the adenosine kinase inhibitors 5'-amino-5'-deoxyadenosine (0.2 microM) or 5'
      iodotubercidin (0.01 microM) with a low concentration of the adenosine deaminase
      inhibitor 2'-deoxycoformycin (0.2 microM) produced additive potentiations of NMDA
      evoked adenosine release from slices of rat parietal cortex. However,
      combinations of low concentrations of 5'-amino-5'-deoxyadenosine (0.2 microM) or
      5'-iodotubercidin (0.01 microM) with a maximal concentration of 2'
      deoxycoformycin (200 microM) produced supra-additive potentiation of NMDA-evoked
      adenosine release. These findings suggest that such combinations of adenosine
      kinase inhibitors with adenosine deaminase inhibitors may provide useful
      strategies for developing therapies to treat disorders associated with excessive
      NMDA receptor activation, such as seizures, ischemic damage and neurodegenerative
      diseases.

PMID- 9600646
TI  - Preclinical pharmacology of B-20991, a 5-HT1A receptor agonist with anxiolytic
      activity.
AB  - The purpose of this study was to characterize the pharmacological effects of 2
      [[4-(o-methoxyphenyl)piperazin-1-yl]methyl]-1,3-dioxoperhydro imidazo[1,5
      a]pyridine (B-20991) by using several biochemical and behavioral assays. Results
      of binding studies showed that B-20991 binds with high affinity to the 5-HT1A
      receptor (Ki = 31.7 +/- 1.7 nM), moderate affinity to 5-HT3 receptor (Ki = 269.4
      +/- 23.2 nM) and low affinity (Ki > 1000) to 5-HT2A receptor, dopamine D2
      receptor, benzodiazepine receptors and alpha1-adrenoceptor. The administration of
      B-20991 produced a dose and time related decrease in mouse rectal temperature,
      increased both lower lip retraction and flat body posture behavioral scores in
      rat, decreased 5-hydroxytryptamine (5-HT, serotonin) neuronal activity in mouse
      hypothalamus, and did not alter dopamine neuronal activity nor locomotor
      activity. The anxiolytic activity of B-20991 was assessed by using both the
      social interaction and light/dark box tests. The results of these tests indicated
      that B-20991 caused a dose-related increase in the social interaction and
      light/dark box behavioral scores. Taken together, these results suggest that B
      20991 is a 5-HT1A receptor agonist that exhibits anxiolytic activity.

PMID- 9600647
TI  - Immunohistochemical evidence of down-regulation of mu-opioid receptor after
      chronic PL-017 in rats.
AB  - In a previous study, mu-opioid receptor binding was decreased by chronic
      treatment of rats with a mu-opioid receptor-selective agonist [CH3Phe3, D
      Pro4]morphiceptin (PL-017) [Tao, P.L., Lee, H.Y., Chang, L.R., Loh, H.H., 1990.
      Decrease in mu-opioid receptor binding capacity in rat brain after chronic PL-017
      treatment. Brain Res. 526, 270-275]. However, there was a lack of correlation
      between the time course of receptor down-regulation and the loss of
      pharmacological effects of the drug. In the current study, we used
      immunohistochemistry to reinvestigate this issue. Male Sprague-Dawley rats were
      chronically treated with PL-017 i.c.v. for 1, 3 or 5 days, using an escalating
      dosage paradigm (0.75-6.0 microg), which resulted in a 1.4 to 32-fold increase in
      the AD50. Rat brains were removed, frozen, coronally sectioned (14 microm) and
      processed for mu-, delta- or kappa-opioid receptor immunohistochemistry by the
      avidin-biotin complex (ABC) method. Significant decreases in OP3 immunodensity
      were found in many brain regions which are enriched with OP3 after chronic
      treatment of PL-017. Time-dependent decreases in OP3 were detected and reached a
      plateau around 3 days of PL-017 treatment. No significant change in OP1 or OP2
      immunodensity after chronic treatment with PL-017 was found. Our conclusion is
      that chronic treatment with PL-017 of rats selectively down-regulates mu-opioid
      receptors in the brain. This may be an important mechanism for PL-017 tolerance.

PMID- 9600648
TI  - Dopamine receptors in the striatum of rats exposed to repeated restraint stress
      and alprazolam treatment.
AB  - Stress-related behaviors are accompanied by modification of a large number of
      neurotransmitters in the brain. Moreover, the binding to GABA(A) receptors does
      not account for all the effects of benzodiazepines. In this study we investigated
      the effect of repeated restraint stress and alprazolam treatment (1 mg/day os) on
      dopamine receptors (Bmax and Kd) in the striatum of adult rats by means of
      quantitative receptor autoradiography. After chronic restraint stress dopamine D1
      receptors (Bmax value) decreased in the accumbens nucleus, whereas dopamine D2
      receptors were not modified in any investigated area. After alprazolam treatment,
      a considerable increase in both dopamine D1 and D2 receptors in the striatum was
      observed. Chronic immobilization stress together with alprazolam treatment re
      established dopamine D1 receptor density to control values in the accumbens
      nucleus and olfactory tubercle, whereas it resulted in an increase in dopamine D2
      receptors comparable to that elicited by alprazolam treatment alone.

PMID- 9600649
TI  - Effects of CDP-choline administration on brain striatum platelet-activating
      factor in aging rats.
AB  - Cytidine 5'-diphosphocholine (CDP-choline) is a precursor in platelet-activating
      factor (PAF) biosynthesis and it is used in the treatment of diseases of the
      central nervous system. PAF levels in the striatum of aged (19 months) rats were
      67% lower than those found in young (2 months) animals. Chronic treatment of aged
      rats with CDP-choline (500 mg/kg per day) reduced these PAF levels by more than
      65% with respect to those of untreated aged rats after 8 days of treatment. PAF
      subsequently stabilized at these low levels as treatment continued. These results
      suggest that some effects of CDP-choline could be mediated by changes in brain
      PAF levels.

PMID- 9600650
TI  - Synergistic effect of calcitonin gene-related peptide on adenosine-induced
      vasodepression in rats.
AB  - The action of calcitonin gene-related peptide (CGRP) on the vasodepressor
      response to adenosine was investigated in anesthetized rats. I.v. bolus
      injections of adenosine (1-100 microg/kg), acetylcholine (0.05-0.4 microg/kg),
      isoproterenol (1-30 ng/kg), nitroglycerin (0.3-10 microg/kg) and diltiazem (10
      300 microg/kg) produced dose-dependent decreases in blood pressure, accompanied
      by changes in heart rate. Only the vasodepressor response elicited by adenosine,
      among the agents tested, was significantly enhanced by i.v. infusion of either
      CGRP (1 ng/kg per min) or cromakalim (0.1 microg/kg per min), which possesses
      glibenclamide-sensitive K+ channel opening activity. After i.v. treatment with
      glibenclamide (20 mg/kg), the vasodepressor responses not only to adenosine but
      also to CGRP (0.5 microg/kg) and cromakalim (30 microg/kg) were significantly
      reduced, while those to acetylcholine and isoproterenol remained unchanged. The
      result indicates that the enhancement of the adenosine-induced vasodepression by
      CGRP, like that elicited by cromakalim, seems to be mediated at least partly
      through ATP-sensitive K+ channel activation.

PMID- 9600651
TI  - Membrane potential of mesenteric artery from carvedilol-treated spontaneously
      hypertensive rats.
AB  - The effects of chronic treatment of stroke-prone spontaneously hypertensive rats
      (SHRSP) with carvedilol, an antihypertensive agent which has both alpha- and beta
      adrenoceptor-blocking actions, on membrane potential and relaxation of mesenteric
      resistant artery were studied. Five-week old SHRSP were treated with carvedilol
      for three months. At 16 weeks, the resting membrane potential of arteries from
      carvedilol-treated SHRSP was more negative than that of arteries from untreated
      SHRSP. The magnitude of acetylcholine-induced hyperpolarization in arteries from
      carvedilol-treated SHRSP was not different from that of arteries from untreated
      SHRSP. In the presence of noradrenaline, the membrane potential of arteries from
      carvedilol-treated SHRSP was more negative than that of arteries from untreated
      SHRSP. The membrane potential of arteries from carvedilol-treated SHRSP in the
      presence of noradrenaline and acetylcholine was more negative than that of
      arteries from untreated SHRSP. The acetylcholine-induced relaxation in
      noradrenaline-precontracted preparations from carvedilol-treated SHRSP was
      greater than that in preparations from untreated SHRSP and was smaller than that
      in preparations from Wistar Kyoto rats. Scanning electronmicroscopy showed that
      carvedilol-treatment decreased the structural abnormalities of the endothelium of
      arteries from SHRSP. These results indicate that chronic carvedilol treatment
      made the membrane potential of smooth muscle more negative and improved
      endothelial function in the mesenteric artery of SHRSP, which may contribute to
      the antihypertensive effect of carvedilol.

PMID- 9600652
TI  - Mechanisms of hydrogen peroxide-induced contraction of rat aorta.
AB  - It has been suggested that reactive oxygen species may be involved in the
      regulation of vascular tone. However, the underlying mechanisms remain to be
      elucidated. The present studies were designed to investigate the contractile
      effects of hydrogen peroxide (H2O2), one of the reactive oxygen species, on
      isolated ring segments of rat aorta with and without endothelium. H2O2 induced an
      endothelium-independent contraction in isolated rat aorta ring segments in a
      concentration-dependent manner at concentrations from 5 x 10(-6) to 5 x 10(-3) M.
      H2O2-induced contractions of denuded rat aorta rings were stronger than those on
      intact rat aorta segments. The contractile effects of H2O2 were inhibited
      completely by 1200 u/ml catalase. The presence of 1.0 microM Fe2+ or 10 microM
      proadifen, a cytochrome P450 monooxygenase inhibitor, potentiated the contractile
      effect of H2O2 on isolated rat aorta segments. 1 mM deferoxamine (a Fe2+
      chelator) or 100 microM dimethyl sulfoxide (a hydroxyl radical scavenger)
      significantly attenuated the vessel contractions induced by hydrogen peroxide
      plus Fe2+ or hydrogen peroxide itself. Removal of extracellular Ca2+ ([Ca2+]0),
      addition of 5 microM verapamil, administration of a protein kinase C inhibitor
      (staurosporine), treatment with an inhibitor of protein tyrosine phosphorylation
      (genistein) or employment of 5.0 microM indomethacin resulted in a significant
      attenuation of the contractile responses of the vessels to H2O2. Pharmacological
      antagonists (e.g. a muscarinic acetylcholine receptor antagonist (atropine), an
      antagonist of histamine H1 receptors (diphenhydramine), an antagonist of
      histamine H2 receptors (cimetidine), an alpha-adrenoceptor antagonist
      (phentolamine), a beta-adrenoceptor antagonist (propranolol) and an antagonist of
      serotonin receptor (methysergide)) did not inhibit or attenuate the contractions
      induced by H2O2. Exposure of primary aortic smooth muscle cells to H2O2 (5 x 10(
      6) to 5 x 10(-3) M) produced significant rises of intracellular Ca2+ ([Ca2+]i)
      within 20 s. Employment of 1.0 microM Fe2+ markedly enhanced the increment in
      [Ca2+]i in the smooth muscle cells. 10 microM proadifen treatment failed to alter
      the hydrogen peroxide-induced increment in [Ca2+]i of the smooth muscle cells.
      However, the presence of 5 microM indomethacin significantly attenuated the rise
      in [Ca2+]i in smooth muscle cells. The present results suggest that H2O2 can
      induce contractions of rat aorta segments, at pathophysiological concentrations,
      which are Ca2+-dependent. Hydroxyl radicals (.OH), cyclooxygenase products,
      protein kinase C and products of protein tyrosine phosphorylation appear to play
      some role in hydrogen peroxide-induced contractions. Metabolites catalyzed by
      cytochrome P450-dependent enzymes (upon treatment with hydrogen peroxide) appear
      to exert a vasodilator effect on rat aorta segments. Lastly, some unidentified
      mediators, produced by a cytochrome P450 inhibitor (proadifen), during hydrogen
      peroxide treatment, appear to play some role in contraction of vascular smooth
      muscle of rat aorta segments in vitro.

PMID- 9600653
TI  - Interaction between peroxynitrite and L-cysteine: effects on rat aorta.
AB  - In rings of rat aorta previously exposed to peroxynitrite (1 mM), L-cysteine and
      its analogues containing, but not those lacking, a thiol group produced a
      powerful transient relaxation. This relaxation is likely to result from the
      release of nitric oxide from a nitrated/nitrosated compound formed following
      reaction of peroxynitrite with a component of the tissue or bathing medium.
      Furthermore, when peroxynitrite was pre-mixed with L-cysteine a new relaxant
      species was formed. Analogues of L-cysteine with a free thiol reacted with
      peroxynitrite to form species with similar relaxant potencies. Analogues lacking
      a thiol formed products with relaxant activity, but less than with L-cysteine.
      Analogues with a free amino but no thiol or carboxylic functions formed products
      with potencies similar to those lacking only the thiol. If the amino is
      substituted and the thiol removed, no relaxant activity was generated. Thus,
      peroxynitrite reacts with L-cysteine to form a novel relaxant whose activity
      derives mainly from formation of its S-nitrosothiol, with a lesser component
      perhaps from an N-nitroso derivative.

PMID- 9600654
TI  - Role of nitric oxide and platelet-activating factor in the initiation of
      indomethacin-provoked intestinal inflammation in rats.
AB  - The effect of indomethacin following the concurrent administration of the nitric
      oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on acute
      intestinal microvascular permeability has been investigated in the rat.
      Administration of indomethacin (10 mg/kg, s.c.) or L-NAME (10 mg/kg, s.c.) alone
      did not affect jejunal and ileal vascular permeability over a 12 h period, as
      determined by the leakage of radiolabelled serum albumin. By contrast, when
      indomethacin (10 mg/kg, s.c.) was injected concurrently with L-NAME (2-10 mg/kg,
      s.c.) significant time-dependent plasma leakage occurred in intestinal tissues
      over 12 h, being apparent within 1 h. Pretreatment with L-arginine (300 mg/kg,
      s.c.) 15 min prior L-NAME prevented these changes in microvascular permeability.
      Likewise, pretreatment with the platelet-activating factor receptor antagonist,
      WEB 2086 ((3-[4-(2-chlorophenyl)-9-methyl-6H-thienol[3,2-f][1,2,4]triazolo- [4,3
      a][1,4]diazepine-2-yl]-1-(4-morpholynil)-1-propanone), 0.1-1 mg/kg, s.c.) dose
      dependently attenuated such damage. These findings suggest that following
      indomethacin administration, the early inhibition of NO synthase leads to acute
      microvascular injury involving platelet-activating factor in the rat jejunum and
      ileum, indicating a protective role of NO, formed by constitutive NO synthase.

PMID- 9600655
TI  - Desmopressin-induced dog ciliary artery relaxation.
AB  - In isolated dog posterior ciliary arteries contracted with prostaglandin F2alpha,
      desmopressin (10(-10) to 10(-8) M), a vasopressin V2 receptor agonist, produced a
      concentration-related relaxation, which was reversed to a contraction by removal
      of the endothelium. Desmopressin was approximately 1/100 as potent as arginine
      vasopressin. Treatment with NG-nitro-L-arginine, a nitric oxide (NO) synthase
      inhibitor, reversed the desmopressin-induced relaxation to a contraction and the
      addition of L-arginine restored the relaxation. SR49059 ((2S)1-[(2 R3S)-(5-chloro
      3-(2-chlorophenyl)-1-(3,4-methoxybenzene-s ulfony)-3-hydroxy-2,3-dihydro-1H
      indole-2-carbonyl]-pyrrolidine-2-car boxamide), a selective vasopressin V1
      receptor antagonist, suppressed the relaxation. In endothelium-denuded arteries,
      desmopressin-induced contractions were also inhibited by SR49059. It is concluded
      that desmopressin, although much less potent than vasopressin, relaxes ciliary
      arteries via a mediation of NO synthesized from L-arginine in the endothelium.
      Vasopressin V1-receptor Subtypes appear to be involved in the desmopressin
      induced relaxation and contraction.

PMID- 9600656
TI  - The dopamine receptor agonist Z1046 reduces ischaemia severity in a canine model
      of coronary artery occlusion.
AB  - Z1046, (S)-6[[6-[[2-(2-methoxyphenoxy)ethyl]amino]propyl]amino]-5,6,7,8-tetra-h
      ydro-1,2-naphtalenediol dihydrochloride, is an agonist at both dopamine D1 and D2
      receptors. Since stimulation of dopamine D2 receptors inhibits noradrenaline
      release, and because cardiac noradrenaline release has been implicated in the
      genesis of early ischaemia-induced, life-threatening ventricular arrhythmias, the
      effect of Z1046 has been examined for its effects on coronary artery occlusion in
      chloralose urethane anaesthetised mongrel dogs. Z1046 (10 microg kg(-1)
      intravenously or 1 microg kg(-1) by local intracoronary injection) decreased
      heart rate and reduced arterial blood pressure and coronary blood flow, effects
      prevented by the prior administration of domperidone (40 microg kg(-1) i.v.). The
      ischaemic changes induced by a 25-min occlusion of the left anterior descending
      coronary artery (including ST-segment elevation and ventricular ectopic activity)
      were much less marked in those dogs administered Z1046 and survival from the
      combined ischaemia reperfusion insult was increased from 7% to 36% (P < 0.05).
      These effects of Z1046 were partly attenuated by domperidone. We conclude that
      the anti-ischaemic effects of Z1046 are due to inhibition of cardiac sympathetic
      responses. Studies using rat isolated perfused mesenteric vascular bed
      preparations subjected to sympathetic nerve stimulation confirmed that Z1046
      inhibits synaptic transmission without modifying vascular responses to
      noradrenaline.

PMID- 9600657
TI  - Action of polygodial, a sesquiterpene isolated from Drymis winteri, in the guinea
      pig ileum and trachea 'in vitro'.
AB  - This study describes the action of the sesquiterpene polygodial, the major
      constituent isolated from the bark of Drymis winteri in the guinea pig ileum and
      trachea in vitro. Polygodial (5 to 128 microM), added for 20 min, did not affect
      the resting tone of the preparations, but caused graded inhibition, associated in
      some cases with rightward displacement of the acetylcholine, histamine (1 nM to
      10 microM), bradykinin (0.1 nM to 1 microM) and KCl (1 to 100 mM)-contraction
      response curves. When assessed in the guinea-pig trachea, polygodial (5 to 342
      microM) caused significant inhibition of bradykinin (10 pM to 1 microM), 9,11
      dideoxy-9alpha,11alpha-methano-epoxy prostaglandin F2alpha (0.1 to 1000 nM) and
      KCl (1 to 100 mM)-induced contractions, although the action against bradykinin
      was not concentration-dependent. Polygodial (5 to 80 microM) caused a small but
      significant shift to the right of substance P and also the selective agonist of
      tachykinin NK2 receptor [beta-Ala8]neurokinin A-(4-10)-induced contractions in
      guinea pig trachea. This action of polygodial seems to be quite selective towards
      tachykinin NK2 receptors since up to 432 microM, polygodial had no effect against
      contraction caused by tachykinin NK1 receptor agonist, substance P methyl ester.
      When tested in the guinea-pig trachea from animals which had been actively
      sensitised to ovalbumin, polygodial (30 to 40 microM) caused time and
      concentration-dependent inhibition of ovalbumin-mediated contraction. In
      addition, polygodial (85 to 342 microM) inhibited contraction induced by compound
      48/80 (1 to 1000 microg/ml), in the guinea-pig trachea from non-sensitised
      animals. These findings and those from our previous study are consistent with the
      notion that the main sesquiterpene polygodial isolated from the bark of D.
      winteri is responsible for most, if not all, of the relevant pharmacological
      action reported previously for the extract of this plant. Thus, polygodial could
      be of potential value in the development of a new drug for the treatment of
      asthma, allergy and other inflammatory processes.

PMID- 9600658
TI  - Existence of postsynaptic dopamine D2 receptor as an enhancer of contractile
      response in vas deferens.
AB  - Effects of dopamine and (+/-)-2-(N-phenylethyl-N-propyl)amino-5-hydroxy-tetralin
      hydrochloride (N-0434), a dopamine D2 receptor agonist, in the presence of
      prazosin on the ATP- and acetylcholine-induced contraction were investigated in
      the guinea-pig vas deferens in order to test for the existence of postsynaptic
      dopamine receptors. The contraction induced by ATP was potentiated by dopamine
      and N-0434. This potentiation was antagonized by spiperone, a dopamine D2
      receptor antagonist, but not by a dopamine D1 receptor antagonist and an alpha2
      adrenoceptor antagonist. Similar results were also observed by acetylcholine as
      well as ATP. The contraction induced by transmural nerve stimulation in the
      presence of alpha-adrenoceptor antagonists was also potentiated by N-0434, and
      this potentiation was antagonized by spiperone. The results suggest that dopamine
      D2 receptors are located on the postsynaptic site of guinea-pig vas deferens and
      that the contractile responses to ATP and acetylcholine are potentiated via
      activation of dopamine D2 receptor.

PMID- 9600659
TI  - Lecithinized superoxide dismutase attenuates phorbol myristate acetate-induced
      injury in isolated dog lung.
AB  - Lecithinized superoxide dismutase, a lecithin derivative bound to recombinant
      human CuZn superoxide dismutase, has a higher affinity for cells such as
      polymorphonuclear leukocytes and endothelial cells than recombinant human CuZn
      superoxide dismutase has. We determined the protective effects of lecithinized
      superoxide dismutase on the increased microvascular permeability induced by
      phorbol myristate acetate (PMA) in isolated dog lungs. Microvascular permeability
      was assessed by the capillary filtration coefficient (Kf,c) and solvent drag
      reflection coefficient (sigma(f)). PMA (13.3 microg) increased microvascular
      permeability, as evidenced by an increase in Kf,c and the small sigma(f) value.
      Lecithinized superoxide dismutase at both low (4800 U) and high doses (48,000 U)
      inhibited the PMA-induced increase in Kf,c, but only the high dose of
      lecithinized superoxide dismutase attenuated the decrease in sigma(f).
      Recombinant human CuZn superoxide dismutase did not affect the PMA-induced
      increase in vascular permeability at either a low (4800 U) or a high dose (48,000
      U). These findings suggest that lecithinized superoxide dismutase has a
      protective effect against oxygen radical-induced lung injury in isolated dog
      lungs.

PMID- 9600660
TI  - Immunosuppressants enhance superoxide radical/nitric oxide-dependent
      dexamethasone suppression of ischemic paw edema in mice.
AB  - A possible new common action of immunosuppressants, besides suppression of the
      genes for cytokines like interleukin-2, was investigated in in vivo models.
      Dexamethasone (0.1 mg/kg, s.c.) failed to suppress ischemic paw edema in mice 1 h
      after its injection, but maximal suppression was achieved at 3 h (20%) whereafter
      the suppression decreased at 6 and 18 h (11% and 10%). Pretreatment with oral
      FK506 (chemical name is recently donated as tacrolimus, 0.1 mg/kg) resulted in
      38%, 52%, 23% and 17% suppression at 1, 3, 6 and 18 h, respectively. Cyclosporin
      A (1 mg/kg), rapamycin (0.1 mg/kg) and deoxyspergualin (1 mg/kg) showed a similar
      pattern of suppressions after dexamethasone. Transforming growth factor-beta1
      (TGF-beta1, 0.3 microg/kg, i.p.) maintained the suppression elicited by an
      immunosuppressant (42-58%) at 6 h after dexamethasone, whereas transforming
      growth factor-beta1 and/or an immunosuppressant were not suppressive.
      Suppression, irrespective of the agent that elicited it, was blocked by nitric
      oxide (NO) synthase inhibitor, anti-oxidant enzymes and cycloheximide. Endogenous
      nitric oxide or oxyradicals are essential for the action of dexamethasone in
      vivo. The four immunosuppressants bound to specific heat-hock proteins (hsp) in
      the glucocorticoid receptor complex and might enhance the synthesis of anti
      inflammatory protein(s).

PMID- 9600661
TI  - Increased pulmonary vascular permeability and oedema induced by intrathecally
      injected endothelins in rat.
AB  - The intrathecal (i.t.) injection of endothelins to conscious rats was found to
      cause respiratory arrest. To gain some insights into this central phenomenon,
      peripheral vascular permeability and lung oedema were measured after i.t. and
      i.v. injections of these peptides. When injected at T-8 spinal cord level,
      endothelin-1 (65 and 650 pmol) and endothelin-3 (650 pmol) enhanced vascular
      permeability in the lungs by 22-fold and 7-fold, respectively, and caused sudden
      death at the highest dose. Less prominent increases (between 1.4- and 2.2-fold)
      of vascular permeability were observed in other tissues (trachea, kidney, ears,
      skin of hind paws and back skin) with endothelin-1. Endothelin-1 (650 pmol)
      caused a similar increase (27-fold) in lung vascular permeability when injected
      at T-2, although the response was significantly less (P < 0.05) if injected at
      the L-4 (15-fold) spinal cord level. Only endothelin-1 produced lung oedema when
      injected at the T-2 or T-8 level. In contrast, intravenous injection of
      endothelins-1 and -3 (650 pmol) did not produce lung oedema and the lung vascular
      permeability was increased by only 1.4-1.6-fold and all rats survived. The prior
      i.t. injection of 6.5 nmol BQ-123 (cyclo[D-Trp, D-Asp, L-Pro, D-Val, L-Leu]), a
      selective endothelin ET(A) receptor antagonist, prevented the increases of lung
      vascular permeability and oedema and the mortality induced by i.t. endothelin-1
      (650 pmol). Whereas i.v. treatment with phentolamine (2 mg/kg) or pentolinium (25
      mg/kg + 50 mg/kg per h x 15 min) abolished the lung vascular permeability changes
      evoked by endothelin-1 (650) pmol), atropine (1 mg/kg), NG-nitro-L-arginine (50
      mg/kg) or indomethacin (5 mg/kg) had no effect. Moreover, the effects of
      endothelin-1 were attenuated in capsaicin pretreated rats (125 mg/kg, 10 days
      earlier) and almost abolished in rats subjected to sympathectomy with 6
      hydroxydopamine (100 mg/kg, 24-48 h earlier). All these treatments except
      atropine and NG-nitro-L-arginine prevented the endothelin-1-induced lung oedema
      and reduced the lethality by around 50%. These results suggest that the increases
      of pulmonary vascular permeability and oedema induced by i.t. endothelin-1 are
      due to an intense pulmonary vasoconstriction mediated by alpha-adrenoceptors
      following the release of catecholamines in response to the activation of
      endothelin ET(A) receptor in the spinal cord. This central phenomenon seems to be
      reflexogenic, including the involvement of primary afferent C-fibers and spinal
      cord ascending fibers to the brain. Thus, endothelin-1 could play a role in
      neurogenic pulmonary oedema through a central mechanism.

PMID- 9600662
TI  - Effects of JTE-522, a specific inhibitor of cyclooxygenase-2, on the recurrence
      of allergic inflammation in rats.
AB  - JTE-522, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide , is a
      selective inhibitor of cyclooxygenase-2 at the enzyme level (IC50 is 6.4 x 10(-7)
      M for sheep cyclooxygenase-2, but it does not inhibit sheep cyclooxygenase-1 at
      concentrations up to 10(-4) M). In rat peritoneal macrophages in culture, it
      markedly inhibited cyclooxygenase-2-dependent prostaglandin E2 production and
      weakly inhibited cyclooxygenase-1-dependent prostaglandin E2 production, as did
      the selective cyclooxygenase-2 inhibitor NS-398 ([N-2(cyclohexyloxy-4
      nitrophenyl)]-methanesulfonamide). In addition, the anti-inflammatory activity of
      JTE-522 was evaluated, using a model of recurrent air pouch-type allergic
      inflammation in rats. JTE-522, injected into the pouch just after a second
      antigen challenge, suppressed the accumulation of pouch fluid, the infiltration
      of leukocytes and the prostaglandin E2 content in the pouch fluid, as did NS-398
      and indomethacin. These findings indicated that JTE-522 is a selective
      cyclooxygenase-2 inhibitor in cell culture systems and that the suppression by
      JTE-522 of the recurrence of allergic inflammation is due to the inhibition of
      cyclooxygenase-2.

PMID- 9600663
TI  - Structure-activity relationship of furosemide-derived compounds as antagonists of
      cerebellum-specific GABA(A) receptors.
AB  - The Na+-K+-2Cl- cotransporter blocker furosemide inhibits gamma-aminobutyric acid
      (GABA)-gated chloride currents and reverses GABA-mediated inhibition of [35S]-t
      butylbicyclophosphorothionate ([35S]TBPS) binding of the cerebellar alpha6
      subunit-containing GABA(A) receptors much more potently than the cerebrocortical
      non-alpha6 subunit-containing receptors. Of the 44 compounds studied, all
      precursors or derivatives of diuretics, one compound [hydrazinosulfonyl
      furosemide (PF 1885)] reversed 5-microM GABA-induced inhibition of [35S]TBPS
      binding to cerebellar and cerebrocortical receptors. Three other compounds, all
      of which are structurally closely related to furosemide, were selective
      antagonists for the cerebellar receptors comparable to the lead compound. Still,
      the diuretic and GABAergic structure-activity relationships differ, since we
      found potent diuretic structures lacking GABA antagonistic activity. Further
      development of the GABAergic potency of furosemide derivatives can now focus on
      the modification of the carboxyl group, replaceable by tetrazole but not by
      sulfonic or phosphinic acids and the furanyl moiety which could be substituted by
      thienyl and benzyl groups.

PMID- 9600664
TI  - Breast cancer cell response to calcitonin: modulation by growth-regulating
      agents.
AB  - Calcitonin may induce cyclic AMP production by breast cancer cells and inhibit
      their growth. The molecular complex leading to cyclic AMP production in response
      to calcitonin is made of the calcitonin receptor coupled to the adenylate cyclase
      by at least one guanine nucleotide-binding protein (G-protein, of the Gs type).
      Our aim was to determine whether and how the responses of cells to calcitonin
      were modulated by growth-regulating agents not directly acting through the cyclic
      AMP pathway. We found that the cyclic AMP response to calcitonin was reduced
      after preincubation of cells with the mitogens 17beta-estradiol and epidermal
      growth factor (EGF), while it was enhanced after preincubation with the growth
      inhibitors tamoxifen and 1,25(OH)2D3, as well as with an antisense
      oligonucleotide to the proto-oncogene c-myc. Scatchard-plots revealed no
      significant change in the calcitonin receptor number or affinity. On the other
      hand, the cyclic AMP production of cells in response to activators unrelated to
      calcitonin, such as forskolin, a direct adenylate cyclase effector, and
      isoproterenol, a beta-adrenergic receptor agonist, was modulated only weakly or
      not at all by the growth-regulating agents. This suggested that the effects
      observed were essentially calcitonin-specific and associated with events located
      between the calcitonin receptor and the adenylate cyclase. Since a Go- or Gi
      protein has been previously implicated in the calcitonin signal transduction, we
      tested the action of pertussis toxin, a specific inhibitor of these G-proteins.
      Pertussis toxin produced a general increase in the cyclic AMP response of cells
      to calcitonin; moreover, the toxin almost abolished the effect of mitogens and
      antimitogens on that parameter. We conclude that in breast cancer cells, the
      calcitonin receptor and the adenylate cyclase are coupled by at least one Go/Gi
      protein sensitive to growth-regulating agents; this results in a modulation of
      the cyclic AMP response to calcitonin by these agents. On the other hand, the
      growth-inhibitory effect of calcitonin on breast cancer cells was reduced by
      17beta-estradiol and enhanced by tamoxifen. We suggest that this could be a
      consequence of changes in cyclic AMP levels and deserves further investigation.

PMID- 9600665
TI  - Effects of pirmenol on action potentials and membrane currents in single atrial
      myocytes.
AB  - Electrophysiological effects of pirmenol hydrochloride (pirmenol) were
      investigated in single atrial myocytes obtained from rabbit and guinea-pig hearts
      by using a whole-cell clamp technique. Under current clamp conditions, pirmenol
      (2-30 microM) prolonged action potential duration in a concentration-dependent
      manner without affecting resting membrane potential in rabbit atrial myocytes.
      However, in the presence of 4-aminopyridine (4 mM), pirmenol (10 microM) failed
      to prolong the action potential duration further. Pirmenol also suppressed
      acetylcholine-induced hyperpolarization and action potential duration shortening,
      resulting in a significant prolongation of the action potential duration in the
      presence of acetylcholine. Under voltage clamp conditions, pirmenol (1-1000
      microM) inhibited transient outward current (I(to)) in a concentration-dependent
      manner. The concentration for half-maximal inhibition (IC50) of pirmenol on I(to)
      was about 18 microM. Pirmenol did not show the use and frequency dependent
      inhibition of I(to). The voltage dependence of the steady-state inactivation of
      I(to) and the recovery from inactivation were not significantly affected by
      pirmenol. Pirmenol accelerated the inactivation of I(to) and blocked I(to) as an
      exponential function of time, consistent with a time-dependent open channel
      blockade. Pirmenol (30 microM) did not affect the inwardly rectifying K+ current
      significantly, but it decreased the voltage-dependent L-type Ca2+ current by
      about 20%. In guinea-pig atrial myocytes, both acetylcholine and adenosine
      induced a specific K+ current activated by GTP-binding proteins. Pirmenol
      suppressed both the acetylcholine- and adenosine-induced K+ current effectively.
      The IC50 of pirmenol for acetylcholine- and adenosine-induced current was about 1
      and 8 microM, respectively. The present results suggest that pirmenol prolongs
      the action potential duration by primarily inhibiting the transient outward
      current in atrial myocytes. In addition, since pirmenol inhibits acetylcholine-
      and adenosine-induced K+ current, pirmenol may effectively prolong the action
      potential duration in atrial myocytes under various physiological conditions as
      in the whole heart or ischemia.

PMID- 9600666
TI  - Exogenous nitric oxide reduces oxygen consumption of isolated ventricular
      myocytes less than other forms of guanylate cyclase stimulation.
AB  - We tested the hypothesis that increasing cyclic GMP with nitric oxide (NO) would
      reduce cardiac myocyte metabolism less than other forms of guanylate cyclase
      stimulation. The steady state O2 consumption (VO2) of a suspension of ventricular
      myocytes in 2.0 mM Ca2+ isolated from hearts of New Zealand white rabbits was
      measured in a glass chamber using Clark-type oxygen electrode. The cellular
      cyclic GMP levels, determined by radioimmunoassay, were increased by (1) adding 3
      morpholinosydnonimine (SIN-1, 10(-8)-10(-5) M) and nitroprusside (10(-8)-10(-5)
      M), NO donors-soluble guanylate cyclase stimulators; (2) carbon monoxide (CO, 1.5
      x 10(-8)-1.5 x 10(-6) M), soluble guanylate cyclase stimulator and (3) guanylin
      (10(-8)-10(-5) M), particulate guanylate cyclase stimulator. The baseline myocyte
      cyclic GMP level was 86 +/- 13 fmol/10(5) myocytes with a corresponding VO2 of
      268 +/- 21 nl O2/min per 10(5) myocytes. An inverse relationship between cellular
      cyclic GMP levels and VO2 existed in these myocytes. The regression equations for
      the four treatments were: VO2 = -0.45 x [cyclic GMP] + 294.4, r = 0.94 for SIN-1;
      VO2 = -1.46 x [cyclic GMP] + 444.7, r = 0.96 for CO; VO2 = -1.25 x [cyclic GMP] +
      389.1, r = 0.84 for guanylin and VO2 = -0.55 x [cyclic GMP] + 322.8. r = 0.79 for
      nitroprusside. The regression lines of the two NO donors were parallel. A similar
      result was also evident for the regressions of CO and guanylin. However, the
      slopes of both the SIN-1 and nitroprusside regression line were significantly
      less steep than that of either the CO or guanylin lines. Therefore, VO2 is
      reduced less for a similar increase in cyclic GMP with NO donors compared to
      direct stimulation with CO or guanylin. These results suggest that NO has
      metabolic effects on myocytes in addition to its stimulatory effects on cellular
      cyclic GMP.

PMID- 9600667
TI  - Change of endothelin receptor subtype in the MEG-01 human megakaryoblastic cell
      line.
AB  - The aim of this investigation was to determine whether the endothelin receptor
      subtype of a megakaryoblastic cell line (MEG-01) changes during culture passages
      as cells undergo maturation and differentiation. On early-passage cells, binding
      of [125I]endothelin-1 was completely inhibited by 1 microM BQ 123 (cyclo-[D
      tryptophanyl-D-aspartyl-prolyl-D-valyl-leucyl]), but not by sarafotoxin 6C. Also
      the endothelin-1-enhancing effect on [Ca2+]i was prevented by BQ 123, whereas
      sarafotoxin 6C had no effect on [Ca2+]i. In late-passage cells, endothelin ET(B)
      analogs, unlike endothelin ET(A) analogs, competed with binding of
      [125I]endothelin-1. Endothelin ET(B) receptor agonists increased [Ca2+]i while
      the endothelin-1-induced response was inhibited by BQ 788 ([N-[(2R,6S)-2,6
      dimethyl-piperidinocarbonyl]-4-methyl-D-leucyl]-[ N(omega)-(methoxycarbonyl)-D
      tryptophanyl]-D-norleucine), but not by BQ 123, although both endothelin ET(A)
      and ET(B) receptor mRNAs were expressed, as shown by reverse transcriptase
      polymerase chain reaction. These results demonstrate that in MEG-01 cells switch
      from expression of endothelin ET(A) to expression of ET(B) receptors during
      culture. The data also suggest that late-passage MEG-01 cells look like
      platelets, in terms of endothelin receptor subtype.

PMID- 9600668
TI  - Cross-tolerance between endogenous nitric oxide and exogenous nitric oxide
      donors.
AB  - It is still unclear whether cross-tolerance develops between endogenously
      produced nitric oxide and exogenous nitric oxide donors. Thus, cGMP accumulation
      was determined in cultured aortic smooth muscle cells exposed to a nitric oxide
      source. Exposure of human, rat, rabbit, porcine or bovine smooth muscle cells to
      sodium nitroprusside led to a time- and concentration-dependent development of
      tolerance. In rat aortic smooth muscle cells, cross-tolerance developed between
      the sodium nitroprusside and S-nitroso-N-acetylpenicillamine, but not between
      sodium nitroprusside and atriopeptin. In addition, when rat aortic smooth muscle
      cells were treated with endotoxin or interleukin-1beta, they displayed lower
      sodium nitroprusside-induced cGMP accumulation as compared to control cells. When
      rat aortic smooth muscle cells were exposed to sodium nitroprusside for 12 h they
      displayed a decreased ability to accumulate cGMP in response to endothelium
      derived nitric oxide released from bovine aortic endothelial cells. In addition,
      co-cultures of rat aortic smooth muscle cells with bovine aortic endothelial
      cells showed an L-nitroarginine methylester-sensitive decrease in sodium
      nitroprusside-induced cGMP accumulation compared to single rat aortic smooth
      muscle cell cultures. We conclude that cross-tolerance between endothelium
      derived nitric oxide and exogenously applied nitric oxide donors occurs in vitro.

PMID- 9600669
TI  - Differential effects of Ca2+ channel blockers on Ca2+ transients and cell cycle
      progression in vascular smooth muscle cells.
AB  - We examined the differential effects of Ca2+ channel blockers on the elevation of
      the cytosolic Ca2+ concentration ([Ca2+]i) and G0/G1 transition induced by
      platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells in
      primary culture. The phase of the cell cycle was determined by an
      immunocytochemical analysis of cell cycle-specific nuclear antigens. [Ca2+]i was
      monitored by fura-2 microfluorometry. The efficacy of Ca2+ channel blockers for
      the inhibition of [Ca2+]i elevation induced by PDGF (NiCl2 > isradipine >
      verapamil = diltiazem) did not parallel that for the inhibition of cell cycle
      progression induced by PDGF (verapamil = diltiazem > NiCl2 > isradipine). In
      addition, no significant correlation was observed between the extent of [Ca2+]i
      elevation and the extent of G0/G1 transition. We thus conclude that the
      inhibitory effects of Ca2+ channel blockers on the G0)/G1 transition induced by
      PDGF are not simply due to their inhibitory action on the [Ca2+]i elevations but
      instead are due to more complex unknown factors.

PMID- 9600670
TI  - Immune regulation within the central nervous system.
AB  - The brain constitutes an environment that is specifically designed to
      accommodate, regulate and shape immune responses. On one hand, the central
      nervous system (CNS) has traditionally been regarded as an immunologically
      privileged organ, owing to local tissue barrier and immunosuppressive
      microenvironment. On the other hand, activated microglia and astrocytes express
      MHC and adhesion/costimulatory molecules, release reactive oxygen intermediates
      and cytokines, and participate in local immune regulation. Bidirectional
      interactions between immune and neuroglial components occur in response to
      infectious and traumatic lesions. Glial cells may facilitate and amplify immune
      effector mechanisms within the CNS. Cytokines and chemokines within the CNS
      constitute a specialized CNS-cytokine network, and regulate the development and
      recovery from autoimmune diseases within the CNS. The interactions between glial
      cells and lymphoid cells are constituents of a complex immune regulatory system
      within the CNS. New data on the cross-talk between the CNS and the immune systems
      are envisaged, and followed by an attempt to create a synthesis of current
      knowledge.

PMID- 9600671
TI  - Effect of entorhinal cortex lesion on hippocampal cholinergic system in rat in
      operant learning task as studied by in vivo brain microdialysis.
AB  - An in vivo microdialysis method was used to study the cholinergic alteration of
      the hippocampus in entorhinal cortex-lesioned rats performing a positive
      reinforcement operant learning task. Rats with bilateral entorhinal cortex
      lesions were implanted with a dialysis probe into the hippocampal CA3 after ten
      learning sessions. After 7 days, the bilateral entorhinal cortex-lesioned rats
      showed impaired acquisition of positive reinforcement operant learning. The basal
      level of the acetylcholine efflux decreased within 30 min before the beginning of
      a learning session. The hippocampal acetylcholine efflux showed a significantly
      diminished increase and rapidly returned to the basal level during the 60 min
      after the beginning of a learning session. These results suggested that enorhinal
      cortex lesion may cause damage to the hippocampal cholinergic system with
      disruption of the entorhinal cortex-hippocampus relay passage.

PMID- 9600672
TI  - Early complete recanalization in internal carotid artery embolism treated with
      high-dose t-PA: a sequential angiographic study in a novel model of embolism in
      rats.
AB  - Complete early recanalization rate of human internal carotid artery embolic
      occlusion treated with thrombolytic drugs is low. To study factors related with
      this difficulty to recanalize we have developed a novel model of rat ica embolism
      using a fragment of human embolus. In 50 male Wistar rats the ica was embolized
      through the external carotid artery with a fragment of an embolus obtained from a
      human embolectomy passed through a catheter of 0.8 mm diameter. Recanalization
      was assessed by sequential angiograms from 15 to 120 min after embolization.
      Reperfusion was classified according to TIMI grades. Emboli of either 1 (group 1)
      or 2 mm (group 2) in length were cut. In group 1, four groups of nine animals
      each were treated, 15 min after embolization, with i.v. t-PA at doses of 1 mg/kg,
      10 mg/kg and 20 mg/kg or saline. In group 2 there was one control group of seven
      animals treated with saline and another of seven animals treated with 10 mg/kg t
      PA. Complete recanalization (TIMI grade 3) within the first 30 min was present in
      two animals treated with 10 and 20 mg/kg. Complete recanalization within the
      first 60 min was present in 0% of controls and animals treated with 1 mg/kg and
      in 44% of the 10 and 20 mg/kg groups (P<0.05 in chi-square test). Incomplete
      recanalization (TIMI grades 0, 1 and 2) occurred in 33%. In group 2 total
      recanalization occurred in 1/7 controls and in 3/7 animals receiving 10 mg/kg of
      t-PA. Early (60 min) complete i.v. t-PA induced internal carotid artery embolic
      recanalization is low with standard doses and increases moderately when high
      doses are used. Further increases in the dose do not improve recanalization rate,
      which is not clearly influenced by embolus size. Complete recanalization within
      30 min, the period after which infarction develops in the rat, is uncommon in our
      model.

PMID- 9600673
TI  - Changes in brain organic osmolytes in experimental cerebral ischemia.
AB  - The cell volume is regulated not only by inorganic ions, but also by organic
      osmolytes, such as amino acids, methylamines, and polyhydric alcohols (polyols).
      Using proton nuclear magnetic resonance spectroscopy (1H-NMR), we measured the
      tissue concentrations of amino acids (alanine, aspartate, gamma-aminobutyric acid
      (GABA), glutamate, glutamine, N-acetyl-aspartate (NAA), taurine), methylamines
      (glycerophosphorylcholine (GPC), creatine+phosphocreatine (total creatine, tCr)),
      and polyols (myo-inositol) in the rat brain after middle cerebral artery
      occlusion (incomplete focal ischemia) or after decapitation (complete global
      ischemia). The total osmolytes expressed as a sum of total amino acids, total
      methylamines, and total polyols were significantly decreased at 24 h of focal
      ischemia (58.7% of control value, P=0.0025) whereas they were not changed
      following decapitation. The water content was increased from control value of
      77.9%-84.1% after focal ischemia (P<0.0001) but not after decapitation. These
      results suggest that the brain organic osmolytes are involved in the process of
      edema formation following focal cerebral ischemia. Further elucidation of the
      cellular mechanisms regulating these organic osmolytes in cerebral ischemia may
      promote greater understanding of the pathophysiology involved in the evolution of
      brain edema.

PMID- 9600674
TI  - Spinal cord GLT-1 glutamate transporter and blood glutamic acid alterations in
      motor neuron degeneration (Mnd) mice.
AB  - This study characterizes for the first time neurochemical mechanisms in Mnd mice,
      initially described as a model of motor neuron disease and more recently proposed
      as a model for neuronal ceroid lipofuscinosis. A selective decrease (-30%) of
      [3H]glutamate uptake was found in spinal cord but not cortical synaptosomes of
      Mnd mice aged 28 weeks, when they show histopathological alterations, complete
      blindness and moderate neurological deficits. In spite of the widespread presence
      of stored material in neurons in many brain regions and spinal cord, the active
      transport of [3H]serotonin, [3H]dopamine and depolarization-induced [3H]serotonin
      release were not affected. Spinal EAAC1 glutamate transporter protein was
      significantly decreased in some but not all aged mice by 36% on average, possibly
      due to the loss of motor neurons. GLT-1 immunoreactivity was reduced by 34% in 28
      week-old Mnd mice, while GLAST immunoreactivity was not affected. In Mnd mice
      aged 14 weeks, when there was no apparent alteration of motor function, the
      defect in the glial transporter protein GLT-1 was similar to that in 28-week-old
      mice (25%). Blood glutamic acid concentration was increased in Mnd mice aged 14
      22 weeks. We suggest that the early decrease of GLT-1 protein might raise the
      extrasynaptic glutamic acid concentration, and contribute to the loss of motor
      neurons in affected mice, resulting in low [3H]glutamate uptake, low EAAC1
      immunoreactivity and neurological deficits.

PMID- 9600675
TI  - Aluminum decreases the magnesium concentration of spinal cord and trabecular bone
      in rats fed a low calcium, high aluminum diet.
AB  - Current epidemiological surveys in the Western Pacific (Guam, and Kii Peninsula
      and West New Guinea) have suggested that low calcium (Ca), magnesium (Mg) and
      high aluminum (Al) and manganese (Mn) in river, soil and drinking water may be
      implicated in the pathogenetic process of foci of amyotrophic lateral sclerosis
      (ALS) and parkinsonism-dementia (PD). The condition of unbalanced minerals was
      experimentally mimicked in this study using rats. Male Wistar rats, weighing 200
      g, were maintained for 60 days on the following diets: (A) standard diet, (B) low
      Ca diet, (C) low Ca diet plus high Al. Magnesium concentrations were determined
      in spinal cord and trabecular bone using inductively coupled plasma emission
      spectrometry (ICP). In the experimental group maintained on a low Ca, high Al
      diet, magnesium concentration of the spinal cord was lower than the group fed a
      standard diet. Also, magnesium concentration of lumbar vertebra showed lower
      values in the experimental group fed a low Ca, high Al diet than did those on a
      standard diet or low Ca diet without supplemental aluminum. Our data indicate
      that low Ca, high Al diet influences Mg concentration in bone and central nervous
      system (CNS) tissues and that a low Ca, high Al diet diminishes Mg in bone and
      CNS tissues, thereby inducing loss of calcification in bone and degeneration of
      CNS tissue due to alteration of the normal biological effects of Mg.

PMID- 9600676
TI  - Shift from hypermetria to hypometria in an aberrant recovery following cerebellar
      infarction.
AB  - Cerebellar hypermetria, a classical sign designating the overshoot when the
      patient attempts to reach rapidly an aimed target, is associated with an
      imbalance between timing and/or intensity of agonist and antagonist EMG
      activities. Recovery of hypermetria following a cerebellar ischemia or hemorrhage
      has been demonstrated to take place in a multistage process, but aberrant
      recovery following a cerebellar stroke has not been described previously. We
      report an 85-year-old woman presenting an abnormal recovery following a
      cerebellar infarction. We identified three successive stages. At stage 1, fast
      wrist flexion movements were severely hypermetric and associated with three EMG
      defects: a delayed onset latency of antagonist EMG activity, a reduction of
      intensity of the agonist EMG activity and a depression of intensity of antagonist
      EMG activity. At stage 2, movements were characterized by terminal oscillations
      around the target and the onset latency of the antagonist activity had returned
      to normal. At stage 3, movements were markedly hypometric, the intensity of the
      antagonist EMG activity had returned to normal, while the intensity of the
      agonist EMG activity remained abnormally low. This case illustrates an abnormal
      reprogramming of the EMG triphasic pattern, resulting in the shift from severe
      hypermetria to severe hypometria.

PMID- 9600677
TI  - Clinical and molecular genetic study in seven Japanese families with
      spinocerebellar ataxia type 6.
AB  - We report on seven Japanese families with spinocerebellar ataxia type 6 (SCA6)
      carrying small CAG repeat expansions in the calcium channel alpha1A subunit gene.
      The number of the expanded CAG repeat, ranged from 22 to 25, showed no
      intergenerational instability and had a significant inverse correlation with the
      age of onset. The clinical features of these patients were late onset progressive
      pure cerebellar ataxia with dysarthria and nystagmus, and are consistent with
      autosomal dominant cerebellar ataxia type III (ADCA type III). Magnetic resonance
      imaging scan of the brain demonstrated cerebellar atrophy with no evidence of
      brainstem involvement. We propose that clinical phenotype of SCA6 is compatible
      with ADCA type III and SCA6 is one of the most common types of ADCA in Japan.

PMID- 9600678
TI  - Clinical and laboratory features of myelitis patients with anti-neutrophil
      cytoplasmic antibodies.
AB  - Although perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) are
      associated with vasculitic neuropathy, their association with central nervous
      system (CNS) disorders has not been studied except for one report on optic-spinal
      type of multiple sclerosis associated with serum pANCA. We examined pANCA in sera
      from 98 patients with various CNS disorders, such as 58 MS, 17 myelitis, 12 HTLV
      1 associated myelopathy, and 11 other CNS diseases using indirect
      immunofluorescence methods. The results showed serum pANCA to be positive in five
      patients with a peculiar type of myelitis, including two with MS and three with
      etiology unknown myelitis. All of these ANCA-positive patients were women and had
      acute or subacute myelopathy with various severities. MRI revealed segmental
      swelling of the spinal cord with T2 hyperintensity in the acute stage of the
      disease. Marked pleocytosis (227.8+/-101/mm3) and elevated protein level (128.8+/
      52 mg/dl) in CSF were noted. Four of the patients had anti-nuclear antibodies and
      two had previous histories of symptoms suggesting autoimmune disorders. In a
      search for target antigens of pANCA, myeloperoxidase reactivity was found in the
      sera from two myelitis patients. Clinical and laboratory features of myelitis
      patients with pANCA in the present study are different from those of typical MS
      patients. Further study will be needed to delineate the role of pANCA in the
      pathogenesis of a specific type of myelitis.

PMID- 9600679
TI  - Effects of thalamic hemorrhage on cortical hemodynamic parameters assessed by
      perfusion MR imaging: preliminary report.
AB  - Thalamic lesions may induce a diffuse hypometabolism and subsequent decrease of
      cortical cerebral blood flow (rCBF) and cerebral blood volume (rCBV). Up to now
      PET was used to assess these changes. However this latter method cannot be
      applied routinely to stroke patients because it is expensive and not currently
      available. The purpose of this preliminary study was to evaluate the effects of
      'pure metabolic depression' induced by thalamic stroke on rCBV and rCBF by using
      a non invasive method perfusion-MRI. Two patients experienced aphasia, with motor
      and sensory impairment related to thalamic hemorrhage. Four weeks later, dynamic
      T2*-weighted echo planar imaging was used to produce perfusion-MR images during
      an intravenous bolus injection of gadopentetate dimeglumine. A decrease of
      cortical rCBV and rCBF mainly confined to sensorimotor cortex was observed in
      both cases ipsilateral to the lesion. Although a sequential assessment of this
      abnormalities is needed in a larger series of patients in order to establish
      relevant correlations with neurological status, this preliminary study indicates
      that perfusion-MRI might be a practical and promising tool in the assessment of
      cortical rCBV and rCBF changes.

PMID- 9600681
TI  - Time course of chemokines in the cerebrospinal fluid and serum during herpes
      simplex type 1 encephalitis.
AB  - Chemokines (chemoattractant cytokines) attract and activate specific leukocyte
      subsets. With regard to their expression by brain parenchymal cells, they may
      represent the key molecules that control leukocyte entry into the subarachnoid
      space. In order to evaluate the contribution of chemokines in vivo, we determined
      the levels of MCP-1, MIP-1alpha, RANTES, IL-8, as well as of the sIL-2R in three
      patients with proven herpes simplex encephalitis type 1 (HSE-1). CSF samples were
      drawn by a subarachnoid catheter system throughout the time course of
      hospitalisation. Results were compared to chemokine levels in serum drawn in
      parallel. The clinical status was documented by the Modified Barthel Index and
      correlated with chemokine levels in the CSF. The results were compared with the
      chemokine levels in the CSF of 17 control patients with normal CSF routine
      parameters. High chemokine levels were detectable in the CSF of all HSE-patients.
      MCP-1 peak levels were found at the time of admission, while maximal IL-8 levels
      occurred 4 to 8 h later. The levels of MIP-1alpha and RANTES were lower than
      those of MCP-1 with a maximum at the time of admission. In all patients the
      levels of the sIL-2R increased later in the time course, at 14 to 20 h after
      admission. When the levels of MCP-1 were compared with the clinical status by
      Modified Barthel Index, we found a high reciprocal correlation (r=-0.82). Routine
      CSF parameters, such as leukocytes, albumin and immunoglobulins did not correlate
      with the clinical status. Chemokine levels in serum were found to be close to the
      detection limits of the ELISA systems. Our data suggest that chemokines play an
      important role in the pathogenesis of HSE. They may be useful parameters to
      monitor the stage and severity of the disease. The late increase of sIL2-R levels
      may indicate the beginning of the reconstitution phase.

PMID- 9600680
TI  - An immunohistochemical study of centenarian brains: a comparison.
AB  - To evaluate the pathology of centenarian brains, which would reflect the ultimate
      stage of the aging process, 13 centenarians (M:F=1:12; mean+/-SD, 101.5+/-1.5
      years) from the consecutive autopsy series were studied. None had severe dementia
      compatible with Alzheimer's disease (AD). As younger controls, 20 nondemented
      (ND) individuals (79.8+/-3.2 years) and 20 AD patients (80.8+/-3.0 years) were
      selected. In addition to the routine examination including methenamine-Bodian
      staining, an immunohistochemical study was performed, using antibodies to amyloid
      beta protein, tau, ubiquitin, glial fibrillary acidic protein (GFAP),
      synaptophysin, and Ki-MIP (a marker of the microglial and perivascular cells). No
      centenarian subjects satisfied the neuropathological criteria for definite AD.
      The densities of senile plaques and neurofibrillary tangles (NFTs) were
      significantly lower in almost all examined subdivisions than the AD patients, and
      tended to be higher than the ND subjects. Cerebral amyloid angiopathy of the
      centenarian was less severe than the AD patients, as well as the proliterations
      of GFAP-positive astrocytes and Ki-MIP-positive microglial cells, and the loss of
      synaptic terminal density. The relative mildness of the age-related morphological
      changes in the centenarians compared with the AD patients supports the idea that
      AD would not be the ultimate condition of the aging process, but would develop
      through the switching to the pathological process.

PMID- 9600682
TI  - Ability to remove immunoglobulins and anti-ganglioside antibodies by plasma
      exchange, double-filtration plasmapheresis and immunoadsorption.
AB  - In Japan, patients with Guillain-Barre (GBS) and Fisher's (FS) syndromes often
      receive plasma exchange (PE), double-filtration plasmapheresis (DFPP), or
      immunoadsorption (IA). To determine whether DFPP and IA are as effective as PE,
      we compared their abilities to remove immunoglobulins and anti-ganglioside
      antibodies. Plasma samples were obtained from 55 GBS patients and 53 FS patients,
      before and after each session of the treatments. PE decreased the IgG
      concentration more than DFPP did, its abilities to remove anti-ganglioside IgG
      antibodies in PE markedly being superior to the abilities of the other
      plasmaphereses. IA on a tryptophan-immobilized column adsorbed anti-ganglioside
      IgG antibodies more effectively than IA on other affinity columns.

PMID- 9600683
TI  - Perfusion and thallium single photon emission computed tomography in herpes
      simplex encephalitis.
AB  - This is the first report on 201thallium-single photon emission computed
      tomography (201Tl-SPECT) brain scan of a patient with herpes simplex encephalitis
      (HSE). The presented 201Tl-SPECT observations are correlated with 99mtechnetium
      hexamethylpropylene amine oxime (99mTc-HMPAO) perfusion SPECT and magnetic
      resonance imaging (MRI) findings. Brain 99mTc-HMPAO perfusion SPECT reveals a
      hyperperfusion in the right temporal lobe with extension to the parietal lobe and
      a hypoperfusion in the ipsilateral occipital lobe. 201Tl-SPECT shows a fixation
      in the right temporal lobe coinciding with the gadolinium enhancement on MRI. The
      right occipital lesion shown by gadolinium captation on MRI and hypoperfusion on
      99mTc-HMPAO perfusion SPECT was not evident on the 201Tl SPECT. These findings
      could illustrate that the lesions might be different pathophysiologically.

PMID- 9600684
TI  - An atypical case of adult Moyamoya disease with initial onset of brain stem
      ischemia.
AB  - We present an atypical case of adult moyamoya disease whose clinical onset
      consisted of ischemic symptoms of the brain stem. She initially presented with
      left hemisensory disturbance caused by a pontine lesion, followed by a myelopathy
      of the upper cervical spinal cord. Eight months later, she presented with left
      hemiplegia and disturbed consciousness. Magnetic resonance angiography showed
      significant narrowing of both horizontal portions of the middle cerebral arteries
      (M1). Conventional angiography revealed bilateral occlusion of the internal
      carotid arteries. Her anterior circulation was supplied from the vertebro-basilar
      system through Moyamoya vessels and leptomeningeal collaterals. The intracranial
      steal phenomenon was thought to be the reason for the preceding events in the
      brain stem and upper cervical spinal cord. In addition, transcranial color-coded
      duplex sonography (TCCS) showed identical findings to conventional angiography
      with antegrade flow in the proximal M1 and retrograde flow in the distal M1.
      Thus, TCCS was useful for diagnosing the M1 occlusion in this case of Moyamoya
      disease.

PMID- 9600685
TI  - The high alkaline fraction on isoelectric focusing of cerebrospinal fluid is
      cystatin C.
AB  - A high alkaline fraction with a pI of 9.2 is sometimes seen on isoelectric
      focusing patterns of cerebrospinal fluid. The appearance of this fraction mainly
      depends on the type of concentrators used to prepare the cerebrospinal fluid
      samples, prior to isoelectric focusing. The amino acid sequence of the high
      alkaline fraction showed sequence identity to cystatin C, a cysteine protease
      inhibitor with a pI of 9.2-9.3 and a molecular mass of 13.4 kDa. In addition, on
      Western blot the high alkaline fraction was recognized by an antibody, directed
      against cystatin C. Taken together, the present findings demonstrate that the
      high alkaline fraction is cystatin C.

PMID- 9600686
TI  - HTLV-I-associated myelopathy associated with multi-organ inflammatory disease: a
      case report.
AB  - We report a 73-year-old man with human T-lymphotropic virus type I (HTLV-I)
      associated myelopathy (HAM) complicated with multi-organ inflammatory disease,
      including Sjogren's syndrome, interstitial cystitis, and uveitis. The presence of
      HTLV-I proviral DNA in peripheral blood mononuclear cells (PBMC), cerebrospinal
      fluid, salivary gland, mucosa of urinary bladder, and aqueous humor was confirmed
      by polymerase chain reaction using HTLV-I pX region primer. Western blot analysis
      revealed the presence of anti-HTLV-I antibodies in serum, CSF, saliva, and urine,
      suggesting replication of HTLV-I in each tissue. A high load of HTLV-I proviral
      DNA (20 copies out of 100 PBMC) was present, associated with increased
      spontaneous proliferation of peripheral blood lymphocytes (24,747 cpm). Our
      results suggest that the high load of HTLV-I in patients with HAM may potentially
      induce systemic inflammation in several organs.

PMID- 9600687
TI  - Middle cerebral artery occlusion after recent Mycoplasma pneumoniae infection.
AB  - Stroke is a rare complication of Mycoplasma pneumoniae infection although recent
      studies suggest that infection may be a risk factor of acute ischemic stroke. We
      report a 5-year-old girl who had a stroke 10 days after M. pneumoniae infection.
      This is the first case of documented middle cerebral artery occlusion after
      Mycoplasma infection in children. In this article, we review other published
      reports on this topic and discuss the possible underlying mechanisms of the
      middle cerebral artery occlusion.

PMID- 9600688
TI  - Suppression of arsenic-induced chromosome mutagenicity by antimony.
AB  - Arsenic and antimony are two semimetals sharing some chemical as well as
      toxicological properties. Both elements are clastogenic but not point mutagenic
      in their trivalent state of valency. Environmental exposure to arsenic was proven
      to be associated with increased rates of various types of cancers. Antimony is
      suspected to be carcinogenic to humans. Arsenic and antimony can be found as
      environmental co-contaminants resulting in co-exposure to man. However, in most
      regions where arsenic was found in elevated environmental amounts, it was not
      investigated whether an additional exposure to antimony was predominating. In
      this study, the chromosome mutagenicity induced by arsenic(III) was significantly
      suppressed by antimony(III) in the micronucleus test with V79 cells. The results
      demonstrate the necessity to identify putative environmental co-contaminations of
      antimony in the regions contaminated with arsenic and to determine the impact of
      antimony co-exposure on arsenic genotoxicity and carcinogenicity in man in vivo.

PMID- 9600689
TI  - Micronuclei and fluctuating asymmetry in brown trout (Salmo trutta):
      complementary methods to biomonitor freshwater ecosystems.
AB  - In this work we measured both micronuclei number in kidney erythrocytes and
      fluctuating asymmetry in wild brown trout (Salmo trutta), caught in different
      fluvial ecosystems of Asturias (northern Spain) characterized by different levels
      of anthropic influence. Brown trout samples from rivers with high anthropic
      influence possessed significantly higher averages of both micronuclei and
      fluctuating asymmetry than brown trout samples from less anthropic-influenced
      rivers. These findings demonstrated the sensitivity of the micronucleus test in
      kidney erythrocytes to biomonitor freshwater ecosystems. The positive association
      found between micronuclei average and fluctuating asymmetry at the populational
      level suggests that fluctuating asymmetry tests could be potential indicators of
      environmental threat. Variation of fish asymmetry with ageing indicates that
      fluctuating asymmetry surveys of wild populations should be carried out in trouts
      of the same age class.

PMID- 9600690
TI  - Aneuploidy and diploidy rates in sperm of five men after three-colour
      hybridization: indication of X chromosome-associated autosome 2 aneuploidy.
AB  - The frequencies of aneuploidy and diploidy for chromosomes 2, X and Y in sperm
      nuclei of five nonsmoking normal donors were assessed by three-colour
      fluorescence in situ hybridization. We detected neither significant
      interindividual variability nor age effect (age range of the study group: 26-38
      yr) on the mean frequencies of aneuploid and diploid sperm. Nullisomic sperm were
      observed more frequently than disomic sperm. In addition, sex chromosomal meiotic
      nondisjunction occurred at a higher rate than autosomal nondisjunction, and
      disomic sperm for the sex chromosomes were formed mainly by errors in the second
      meiotic division. Our data indicate that diploidy occurs at a very low frequency
      in comparison with aneuploidy. Furthermore, the overall proportion of X-bearing
      sperm nuclei aneuploid for chromosome 2 is significantly higher than that of Y
      bearing sperm (0.14% vs. 0.05%, respectively; p < 0.001). This finding adds
      further evidence that autosomal aneuploidy can be preferentially associated with
      the presence of one of the two gonosomes.

PMID- 9600691
TI  - In situ assessment of pesticide genotoxicity in an integrated pest management
      program I--Tradescantia micronucleus assay.
AB  - The genotoxicity induced by pesticides applied in an integrated pest management
      (IPM) program was evaluated with the Tradescantia micronucleus assay (Trad-MCN).
      Three pesticide application rates were prescribed as follows: (a) Low, no field
      pesticide spray; (b) Medium, IPM test rate: banded cyanazine plus metolachlor
      (2.7 kg a.i. and 2.3 l a.i./ha of herbicides, respectively); and (c) High, a
      preventative pesticide application program: broadcast cyanazine plus metolachlor
      (same application rates as above) plus chlorpyrifos (1 kg a.i./ha of
      insecticide). The Trad-MCN was employed for the assessment of (a) the formulated
      compounds, singly and in combinations; (b) pesticide residues extracted from
      soils sampled before and after application, and (c) in situ exposures (14-h
      exposure to pesticide-sprayed field). All pesticides showed clastogenic potency
      at doses between 10 and 50 ppm. Aqueous extracts of the two pesticide-sprayed
      soils were clastogenic, but the unsprayed soil extracts were not. Plants exposed
      in situ to pesticide-sprayed soils (inside a chamber receiving vapors from the
      soil) also showed significant increases in micronuclei frequency in relation to
      controls exposed to unsprayed soil. In general, there was no significant
      reduction in the genotoxic effects from the High to the Medium treatment levels
      of the IPM program. This suggests that the reduction in pesticide application
      rates attained with the implementation of the proposed IPM program was not
      sufficient to abate the genotoxicity of the pesticides, as perceived with the
      sensitive assays employed. The results indicate that replacing genotoxic
      compounds may be the only effective remediation measure to eliminate the risks
      imposed by mutagenic compounds in the agricultural environment.

PMID- 9600692
TI  - In situ assessment of pesticide genotoxicity in an integrated pest management
      program: II. Maize waxy mutation assay.
AB  - The mutagenicity induced by pesticides applied in an integrated pest management
      (IPM) program was evaluated in situ with the maize forward waxy mutation
      bioassay. Three pesticide application rates were prescribed as follows: (1) Low-
      no field pesticide spray; (2) Medium--IPM test rate: banded cyanazine plus
      metolachlor (2.7 kg a.i. and 2.3 l a.i./ha of herbicides, respectively); and (3)
      High--a preventative pesticide application program: broadcast cyanazine plus
      metolachlor (same application rates as above) plus chlorpyrifos (1 kg a.i./ha of
      insecticide). In general, there was no significant reduction in the genotoxic
      effects from the high to the medium treatment levels of the IPM program. This
      suggests that the reduction in pesticide application rates attained with the
      implementation of the proposed IPM program was not sufficient to abate the
      genotoxicity of the pesticides. The results indicate that replacing genotoxic
      compounds may be the only effective remediation measure if concern about
      environmental mutagenesis were to result in changes in agricultural management.

PMID- 9600693
TI  - Chemicals mutagenic in Salmonella typhimurium strain TA1535 but not in TA100.
AB  - The standard Salmonella mutagenicity test uses two strains of Salmonella
      typhimurium (TA1535 and TA100) containing the same base pair substitution
      mutation (hisG46). These strains differ only in that strain TA100 contains the
      plasmid pKM101, whose mucAB gene products enhance SOS mutagenesis. This makes
      strain TA100, in general, the more sensitive of the two for mutagen detection,
      raising the question as to whether or not to include strain TA1535 in the core
      battery of strains in routine testing. Out of 659 chemicals judged as mutagens in
      the S. typhimurium assay when subjected to the National Toxicology Program's
      screening protocol, 36 (5%) were evaluated as positive in strain TA1535 but not
      in strain TA100. Of these, 23 were judged as negative and 13 as equivocal in
      strain TA100, and 5 were positive or equivocal in at least one other strain (TA97
      or TA98). In general, the data on these chemicals indicate that the absolute
      increases in revertants per plate induced in strain TA1535 were too small to have
      been judged as positive if similar increases occurred in strain TA100, which has
      a much higher spontaneous background. For three chemicals (acetaldehyde oxime, 6
      mercaptopurine, and 1,3-butadiene) the absolute increases in revertants in strain
      TA1535 greatly exceeded those in strain TA100. Evaluation of the reproducibility
      of these findings and of the mechanisms and relevance of unique TA1535 positives
      should be useful when decisions are made as to whether this strain should be kept
      as a part of the core battery of strains in the S. typhimurium assay.

PMID- 9600695
TI  - Mutagenesis of a single AT basepair in mice transgenic for PhiX174 am3 cs70 I.
      Spleen and testis.
AB  - Mutations induced in a single AT base pair were studied in spleen and testis by
      using mice transgenic for PhiX174 am3, cs70 and ethylnitrosourea (ENU) as the
      mutagen. The transgenic mice were produced on the C57BL6/J background. The line
      (am54), which carries 50 copies of PhiX per haploid genome integrated in a tandem
      array, was selected for experimental use and was maintained by random breeding.
      The animals for mutagenesis studies were produced by mating homozygous am54 males
      to wildtype C57BL6/J females. Hemizygous male offspring (8 to 10 weeks old) from
      this cross were injected i.p. with 150 mg ENU per kg and were euthanized 3, 10 or
      110 days after treatment. The spontaneous revertant frequency in the spleen was
      1.42 x 10(-6) per plaque forming unit (pfu) and in the testis it was 1.41 x 10(
      6) per pfu. There was no significant difference between the two tissues. In
      spleen, it was not until 110 days after ENU treatment that the average revertant
      frequency among treated animals was significantly higher than the revertant
      frequency among the control animals. In spleen, the induced frequency of basepair
      substitutions in the center AT basepair in the am3 nonsense codon was 2 x 10(-6).
      Also at this post-injection interval the variance of revertant frequencies in the
      spleen was not different from control variance. In testis, the average revertant
      frequency 110 days post ENU injection was not significantly different from the
      control. However, two important observations were made regarding the testis data.
      First, one animal had a significantly increased revertant frequency 110 days
      after ENU treatment in comparison to the other four animals in the group that had
      revertant frequencies equal to or lower than the average control frequency.
      Second, the variance of revertant frequencies in the testis among the treated
      animals increased as the post injection period increased. Taken together, these
      observations may indicate that the revertants formed large clusters in one testis
      sample.

PMID- 9600694
TI  - Biological monitoring of young workers exposed to polycyclic aromatic
      hydrocarbons in engine repair workshops.
AB  - Several polycyclic aromatic hydrocarbons (PAHs) are carcinogenic in rodents,
      while exposure to these compounds has been associated with various types of human
      cancer. Engine exhaust and used engine oils are major PAH sources in engine
      repair workshops. Urinary 1-hydroxypyrene (1-OHP) levels and some genotoxicity
      parameters (sister-chromatid exchange, SCE; micronucleus, MN) have been compared
      among engine repair workers (n = 61, age: between 13 and 18) and workers not
      occupationally exposed to PAH (n = 30, age: between 13 and 19). The mean value
      (+/- S.E.) of urinary 1-OHP excretions of workers was 4.71 +/- 0.53 micromol/mol
      creatinine and also mean urinary 1-OHP for controls was found to be as 1.55 +/-
      0.28 micromol/mol creatinine. The mean values (+/- S.E.) of SCE frequency per
      cell in peripheral lymphocytes from the workers and controls were 4.47 +/- 0.09
      and 4.06 +/- 0.16, respectively (p < 0.05). The mean (+/- S.E.) MN (per thousand)
      frequencies in peripheral lymphocytes from the workers and controls were 1.87 +/-
      0.04 and 1.56 +/- 0.06, respectively (p < 0.0001). The effect of smoking for the
      above parameters were also evaluated.

PMID- 9600696
TI  - In vitro and in vivo transformation in rat tracheal epithelial cells exposed to
      diesel emission particles and related compounds.
AB  - The rat tracheal epithelial (RTE) cell transformation assay was performed to
      determine the transforming activity of diesel emission particles (DEPs) and two
      related compounds, 1-nitropyrene (1-NP) and dibenzo(a,i)pyrene (DBP). RTE cells
      were treated with these agents in vitro and in vivo. Transformed cells from foci
      induced by these agents were passaged over 20 times to establish immortal cell
      lines. Results show that (1) DEPs- and 1-NP-induced cell transformation only with
      the in vivo exposure (30-75 mg/kg bw DEPs and 15-60 mg/kg bw 1-NP); (2) positive
      dose-related responses to DBP were found with both in vitro (0.05-0.50 microg/ml)
      and in vivo (7.5-30 mg/kg bw) exposures; (3) the fraction of transformed foci
      becoming cell lines was in the order of 1-NP(25/48) > DBP(8/28) > DEPs(0/30).
      These results indicate that (1) DEPs, 1-NP and DBP are capable of transforming
      rat tracheal epithelial cells, however, the transforming activity of DEPs and -NP
      may be dependent on metabolic activation, and (2) transformed cells induced by
      DEPs have a very low probability, if any, of becoming cell lines.

PMID- 9600697
TI  - Cytogenetic analysis of peripheral lymphocytes in medical personnel by means of
      FISH.
AB  - Genotoxic effects of occupational exposure to cytostatics were investigated in 20
      nurses and physicians working in various departments of one hospital. The group
      was divided into two equal subgroups one of which was involved in the
      administration of cytostatics (exposed subgroup) and the other was not (unexposed
      subgroup). The whole group and the two subgroups were compared with a control
      group of 11 healthy blood donors. Two differently labeled whole chromosome
      painting (WCP) probes specific for the chromosomes 1 and 4 were used
      simultaneously. Chromosome aberrations were classified in terms of the Protocol
      for Aberration Identification and Nomenclature (PAINT) nomenclature. The results
      obtained by the painting method were compared with findings of conventional
      unbanded chromosome analysis. Significant differences in the numbers of
      translocations (FG/100 = 2.25 +/- 1.50 vs. 0.66 +/- 0.21, p < 0.01) and unstable
      chromosome aberrations determined by the conventional method (AB.C/100 = 2.70 +/-
      2.31 vs. 1.63 +/- 1.59, p < 0.05) were found between the exposed subgroup and
      controls. The unexposed subgroup differed from the controls only in the number of
      translocations (FG/100 = 2.93 +/- 2.79 vs. 0.66 +/- 0.51, p < 0.05). No
      significant differences in the number of stable and unstable aberrations were
      found between the exposed and the unexposed subgroups. On the other hand, highly
      significant differences (p < 0.01) were demonstrated by the two methods between
      the whole group (all medical personnel) and the controls. All differences which
      were found to be significant when translocations were compared were also found to
      be significant when total stable chromosome exchanges, i.e., the sum of
      translocations and insertions, were considered. Multicolour chromosome painting
      is apparently a more sensitive method than the conventional metaphase-based
      analysis.

PMID- 9600698
TI  - Genotoxicity evaluation of trimethylbenzenes.
AB  - The three trimethyl isomers of benzene (hemimellitene, 1,2,3-TMB; pseudocumene,
      1,2,4-TMB and mesitylene, 1,3,5-TMB) were investigated for different genotoxicity
      endpoints: in vitro, in the Ames test with Salmonella typhimurium TA97a, TA98,
      TA100 and TA102 strains in the presence and absence of rat liver S9 metabolic
      activation; in vivo, in the micronucleus and sister chromatid exchange (SCE)
      tests with bone marrow cells of Imp:Balb/c mice. Only the isomer of benzene with
      the methyl-group at position 1, 2, 3 was found to have mutagenic effect on S.
      typhimurium cells. Increase in bacterial reversions was observed in four
      conventional strains used in this study, but most clearly in TA97a. The mutagenic
      responses of 1,2,3-TMB with the SalmonellaL tester strains were observed in the
      experiments performed in the absence of enzymatic activation. None of the
      compounds had an influence on the frequency of micronucleated polychromatic
      erythrocytes in bone marrow cells of mice. However, all the three compounds were
      observed to have a cytogenetic potential of increasing the SCE level in these
      cells. Significant responses in SCE induction, compared with the level of those
      changes in corresponding solvent-administered controls, were obtained at three
      test doses of 1,2,3-TMB (730, 1470, 2200 mg/kg) and 1,2,4-TMB (900, 1800, 2700
      mg/kg) and at two doses of 1,3,5-TMB (1800, 2700 mg/kg). These data provided a
      limited evidence for the genotoxic activity of 1,2,3-TMB and inadequate evidence
      for genotoxic activity of 1,2,4-TMB and 1,3,5-TMB.

PMID- 9600699
TI  - Effect of cancer chemopreventive agents on microsome-mediated DNA adduction of
      the breast carcinogen dibenzo[a,l]pyrene.
AB  - Due to the large and expanding number of potential cancer chemopreventive agents,
      there is an increasing need for short term tests to study the efficacy and
      mechanisms of these agents. In this study, we have employed a microsome-mediated
      test system to study the effect of several suspected chemopreventive agents on
      the DNA adduct formation capacity of the potent mammary carcinogen,
      dibenzo[a,l]pyrene (DBP). Bioactivation of DBP by Aroclor 1254-induced rat liver
      microsomes in the presence of calf thymus DNA (300 microg/ml) resulted in the
      formation of one major and six other prominent DNA adducts (324 adducts/10(7)
      nucleotides). These adducts were previously determined to be deoxyadenosine (dA)
      and deoxyanosine (dG)-derivatives of both anti- and syn-DBP-11,12-diol-13,14
      epoxides (DBPDE). Intervention with ellagic acid, chlorophyllin, benzyl
      isocyanate (BIC), oltipraz or genistein (150 microM) strongly diminished DBP-DNA
      adduction by > or = 75%. Linoleic acid, curcumin and butylated hydroxytoluene
      (BHT) also significantly inhibited DBP DNA adduction (26-46%) while N
      acetylcysteine (NAC) had no effect. Moreover, nonenzymatic studies with anti- and
      syn-DBPDE isomers revealed that chlorophyllin, ellagic acid, BIC and BHT may be
      inhibiting DBP-DNA adduction in an enzymatic-independent manner since these
      agents diminished DBPDE-DNA adduction by 30-75%. Genistein, oltipraz and curcumin
      did not diminish DBPDE-DNA adduction and therefore most likely require the
      presence of the microsomal subcellular fraction to inhibit DBP-DNA adduction.

PMID- 9600700
TI  - Pharmacokinetic parameters determined from the clastogenic activity of
      ethylnitrosourea and dimethylnitrosamine in mice in vivo.
AB  - The latency period (LP) and the time of effective activity (TEA) of
      ethylnitrosourea (ENU) and dimethylnitrosamine (DMN) were inferred by comparing
      their kinetics of micronucleated polychromatic erythrocytes (MN-PCE) formation
      with the kinetics induced by radiation. The results indicate that LP and TEA vary
      between ENU and DMN. For ENU, these parameters are very similar to radiation
      indicating a rapid distribution, reaction and elimination. DMN presents a very
      long LP which agrees with the requirement of mutagen activation. The kinetics of
      MN-PCE production caused by DMN showed two peaks; this could be due to the
      presence of two different metabolites, two types of lesions in DNA or two
      mechanisms of MN-PCE formation. These hypotheses do not exclude each other. The
      data presented here support the conclusion that the comparison of MN-PCE
      formation kinetics induced by chemical agents with that caused by radiation
      permits one to estimate the LP and the TEA, and provide information on the
      possible mechanism of action of chemical mutagens.

PMID- 9600701
TI  - Adsorption of a hydrophobic mutagen to cereal brans and cereal bran dietary
      fibres.
AB  - The abilities of brans from the cereals barley, oats, maize, rice, and wheat to
      adsorb in vitro the hydrophobic, environmental mutagen 1,8-dinitropyrene (DNP)
      were investigated using a mutagenicity assay. These brans were obtained from
      known cultivars using defined milling conditions and were chemically
      characterised. The abilities of total and insoluble dietary fibre preparations
      obtained from these brans to adsorb DNP were also investigated. The predicted
      weight of each bran required to adsorb 50% of the added DNP was used to compare
      the adsorptive abilities of the different brans. The brans were ranked in the
      order (most effective to least effective): rice, wheat, maize, barley, and oats.
      The adsorptive abilities of the dietary fibre preparations were not significantly
      different from the bran from which they were prepared. However, if the dietary
      fibres (cell walls) were the only components adsorbing the DNP, we would have
      expected the dietary fibre preparations to have adsorbed more DNP than the
      equivalent unextracted bran. This suggests that other components, probably
      starch, also adsorb DNP in the unextracted brans. It is not known why brans from
      different cereal species differ in adsorptive ability but the lignified cell
      walls in wheat bran may be important in conferring good adsorptive properties to
      this bran. The possible relationship between adsorptive ability and ability of
      the bran from a particular species to protect against colorectal cancer is
      discussed.

PMID- 9600702
TI  - Corticosteroids induce expression of transforming-growth-factor-beta1 mRNA in
      peripheral blood mononuclear cells of patients with multiple sclerosis.
AB  - The mechanisms by which corticosteroids act in the treatment of an acute relapse
      in multiple sclerosis (MS) are not completely known. We investigated the mRNA and
      protein expression of transforming-growth-factor-beta1 (TGFbeta1), a cytokine
      with anti-inflammatory and immunosuppressive potentials, in peripheral blood
      mononuclear cells (PBMC) and serum of 10 patients with an acute relapse of MS
      before, during and after the treatment with 500 mg prednisolone daily over 5
      days. The expression of TGFbeta1-mRNA increased at day 3-5 and declined at day 8
      10. Serum levels of TGFbeta1 demonstrated a comparable course. The present data
      suggest that corticosteroids induce the expression of TGFbeta1 in vivo. This is
      might be an other mechanism by which corticosteroids mediate immunosuppression.

PMID- 9600703
TI  - Lack of over-expression of T cell receptor Vbeta5.2 in myelin basic protein
      specific T cell lines derived from HLA-DR2 positive multiple sclerosis patients
      and controls.
AB  - Based on studies reporting an overexpression of certain V genes in myelin basic
      protein (MBP)-specific T cells from MS patients, immunotherapies targeting single
      TCR (Vbeta5.2, Vbeta6.1) are currently under way. In order to assess the basic
      assumption for one of these therapeutic strategies, i.e. the overexpression of
      Vbeta5.2 by MBP-specific T cells, we analyzed 100 MBP-specific T cell lines (TCL)
      for Vbeta5.2 expression. Only 4 out of 100 TCL expressed Vbeta5.2, and expression
      of this TCR gene is therefore not more frequent than expected from the normal
      peripheral blood distribution.

PMID- 9600704
TI  - Discontinuation of treatment with IFN-beta leads to exacerbation of experimental
      autoimmune encephalomyelitis in Lewis rats. Rapid reversal of the
      antiproliferative activity of IFN-beta and excessive expansion of autoreactive T
      cells as disease promoting mechanisms.
AB  - IFN-beta has recently been shown to exert remarkable beneficial effects on
      disease development in patients with early stage relapsing-remitting MS. The
      specific immune mechanism(s) by which IFN-beta ameliorates this human
      demyelinating disease is at present undefined. One potential mechanism may reside
      in the antiproliferative activity of IFN-beta which may inhibit the expansion of
      autoaggressive T cells thereby limiting disease progression. In the present study
      we investigated whether the administration of recombinant rat IFN-beta (rrIFN
      beta) to Lewis rats with actively induced experimental autoimmune
      encephalomyelitis (EAE) inhibits the expansion of encephalitogenic T cells in
      lymphoid organs and as such may contribute to suppression of disease activity in
      this widely used animal model for MS. Our data show that daily administrations of
      > or = 3 x 10(5) u rrIFN-beta to EAE rats, starting two days before MBP
      sensitization and continued for 10 days led to a dramatic and dose-dependent
      reduction in encephalitogenic T cells in both spleen and inguinal lymph nodes at
      day 8 post-immunization (p.i.). However, the rrIFN-beta-mediated reduction in
      effector T cells did not ameliorate paralytic disease as expected but
      significantly enhanced the severity of EAE. Analyses of lymphoid organs in the
      remission phase of EAE revealed strongly elevated numbers of encephalitogenic T
      cells in rrIFN-beta-treated versus control rats suggesting a rapid reversal of
      the antiproliferative action of rrIFN-beta followed by an overshoot in the
      subsequent expansion of these effector T cells. In conformity with higher numbers
      of encephalitogenic T cells and worsening of disease, animals also showed
      significantly greater perivascular inflammation in the CNS. The relevance of our
      findings in relation to the beneficial effects of IFN-beta in MS is discussed.

PMID- 9600705
TI  - Gangliosides do not elicit experimental autoimmune encephalomyelitis in Lewis
      rats and SJL mice.
AB  - We have studied the ability of gangliosides to induce or ameliorate experimental
      autoimmune encephalomyelitis (EAE) in Lewis rat and SJL mice. None of the animals
      immunized with gangliosides with or without methylated bovine serum albumin
      (MBSA) developed EAE. Gangliosides were also administered simultaneously with
      PLP, but they did not alter the incidence or severity of EAE. However, high doses
      of MBSA could ameliorate or prevent EAE in a dose-dependent manner. T-cell
      responses towards gangliosides and antiganglioside antibodies were also studied.
      In conclusion, in these experimental models gangliosides have no encephalitogenic
      activity and do not alter the course of EAE.

PMID- 9600706
TI  - Interleukin-1 receptor deficiency in the hippocampal formation of (NZB x NZW)F2
      mice: genetic and molecular studies relating to autoimmunity.
AB  - Interleukin-1 receptor (IL-1R) deficiency has been previously described in the
      dentate gyrus of autoimmune NZB and (NZB x NZW) F1 (or BWF1) mice. In this study,
      the genetic and molecular characterization of this defect were investigated in
      BWF2 mice in relation to anti-DNA antibody production and microsatellite D1Nds4
      (near the IL1r1 gene) polymorphism. IL-1R density was quantified in the brain,
      spleen and pancreas, using in vitro quantitative autoradiography with recombinant
      human [125I]-IL-1alpha as the ligand. This study of the dentate gyrus of F2 mice
      revealed three phenotypes: NZW-like, NZB-like and F1-like, which occurred in a
      ratio of 1:1:2, with IL-1R densities of 100%, 17% and 59%, respectively as
      compared to control NZW mice (100%). In contrast, IL-1R densities observed in the
      choroid plexus and peripheral organs were similar. Moreover a high production of
      IgG2a anti-DNA antibodies was observed in F2 mice, as in their parents,
      particularly those with the NZB-like phenotype. Microsatellite mapping of D1Nds4
      revealed polymorphism in both parents and BWF2 mice in relation to the level of
      IL-1R density in the dentate gyrus. In spite of the acute defect in IL-1 binding
      in the dentate gyrus of NZB mice, molecular analysis of IL-1R mRNA (type I, II
      and accessory protein) showed similar amounts of mRNA, measured following RT-PCR
      amplification, in the hippocampal formation of both NZB and control C3H/He mice.
      In conclusion, the transmission of the IL-1R defect in the dentate gyrus of NZB
      mice is monofactorial and the defect appears to be at the post-transcriptional
      level of IL-1R synthesis. The lack of IL-1R in the dentate gyrus seems to
      correlate with some autoimmune characteristics. Correlation of D1Nds4
      polymorphism with the level of IL-1R density suggests that it could be a
      predisposing gene to disease or a marker for other closely linked predisposing
      genes.

PMID- 9600707
TI  - Cytokine production and the pathogenesis of experimental autoimmune neuritis and
      Guillain-Barre syndrome.
AB  - Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barre syndrome,
      GBS) and its animal model experimental autoimmune neuritis (EAN) are prototypes
      of T cell-mediated autoimmune diseases affecting the peripheral nervous system
      (PNS). Perivascular accumulation of macrophages and T lymphocytes in the PNS, and
      high levels systemically of PNS myelin antigen-reactive T cells are
      characteristic features of both diseases, thereby suggesting a pathogenic role
      for immunoregulatory cytokines. Here we summarise recent studies that have
      clearly documented that Th1/Th2/Th3 cytokines are differently upregulated during
      various clinical phases of EAN and GBS. The observations indicate that the role
      of cytokines in immune regulation and autoimmune disease is more complex than a
      simple Th1-Th2 dichotomy would suggest. New treatments may be searched for that
      counteract this complex cytokine imbalance. Treatments with antibodies that
      selectively target certain pro-inflammatory cytokines, as well as with
      immunomodulatory preparations that promote cytokines that beneficially influence
      the disease course should be in focus of future therapeutic trials.

PMID- 9600708
TI  - Role of endogenous pro-enkephalin A-derived peptides in human T cell
      proliferation and monocyte IL-6 production.
AB  - In this paper, we describe that met-enkephalin and/or enkephalin-containing
      intermediary peptides of the prohormone pro-enkephalin A are produced and
      secreted by human peripheral blood T cells and monocytes. The peptides are
      produced after stimulation with the mitogenic monoclonal antibodies anti
      CD2.1/2.2 and anti-CD28. In monocytes, enkephalin synthesis was induced by
      stimulation with lipopolysaccharide. We demonstrate here that these immune cell
      derived enkephalins play an important regulatory role in the immune response. By
      using an anti-sense oligonucleotide strategy we could block the production of
      enkephalins. Blockade of the production of met-enkephalin and enkephalin
      containing intermediary peptides resulted in enhancement of the proliferative T
      cell response and inhibition of monocyte IL-6 secretion. In vitro reconstitution
      of the anti-sense treated cultures with synthetic met-enkephalin or the delta
      type specific opioid receptor agonist deltorphin could reverse inhibition of
      monocyte IL-6 production, suggesting that endogenous enkephalins act via membrane
      opioid receptors. In contrast, addition of met-enkephalin or deltorphin to the
      anti-sense treated T cell cultures did not have any effect on T cell
      proliferation.

PMID- 9600709
TI  - Endocrine regulation of murine macrophage function: effects of
      dehydroepiandrosterone, androstenediol, and androstenetriol.
AB  - In these studies, the in vitro influences of dehydroepiandrosterone (DHEA),
      androstenediol (AED), and androstenetriol (AET) on proinflammatory cytokine
      production from macrophages was examined. From physiologic to pharmacologic
      doses, DHEA suppressed secretion of each pro-inflammatory cytokine while AED had
      little influence on the responses. In sharp contrast, AET augmented TNF-alpha and
      IL-1 secretion while not influencing IL-6 production. Furthermore, the
      antiglucocorticoid activity of DHEA, AED, and AET was also investigated. Co
      culture with AET counteracted the down-regulatory effect of hydrocortisone on LPS
      induced TNF-alpha and IL-1 secretion. These data imply that AET is capable of
      regulating cytokine secretion from macrophages and may function to counterbalance
      glucocorticoid function.

PMID- 9600710
TI  - The expression of complement regulatory proteins by adult human oligodendrocytes.
AB  - In multiple sclerosis, infiltrating T lymphocytes and perivascular microglia may
      initiate demyelinating lesions, but a role for antibody and complement in the
      ensuing inflammatory damage to myelin and oligodendrocytes is likely. In most
      tissues, ubiquitously expressed complement regulatory proteins prevent autologous
      destruction, protecting host cells from the powerful cytolytic activity of
      activated complement. We have studied the surface expression of a comprehensive
      range of complement regulatory proteins by live adult human oligodendrocytes in
      vitro. Only DAF of the activation pathway regulators was expressed, not CR1 or
      MCP. Of the membrane attack pathway regulatory proteins, HRF was not expressed,
      while substantial heterogeneity of CD59 expression by oligodendrocytes was found.
      Clusterin expression was not found. A relative deficiency of protective
      complement regulatory proteins on human oligodendrocytes may contribute to their
      selective damage in multiple sclerosis.

PMID- 9600711
TI  - Enhanced secretion of substance P by cytokine-stimulated rat brain endothelium
      cultures.
AB  - Substance P (SP) was analyzed in rat brain endothelium cultures after cytokine
      stimulation. SP secretion was found after stimulation with high doses of
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). High
      doses of interferon-gamma (INF-gamma) had no effect on this secretion. Elevated
      SP release was found to be associated with mRNA expression of beta
      preprotachykinin (beta-PPT), precursor of SP, in the cells. Under cytokine
      stimulation, part of SP was bound to brain endothelial cell surface, suggesting
      the existence of an autocrine network for this neuropeptide. These findings
      suggest that SP may have an immunomodulatory action at the blood-brain barrier
      during inflammatory and autoimmune processes in the central nervous system.

PMID- 9600712
TI  - T-cell heterogeneity in muscle lesions of inclusion body myositis.
AB  - In the muscle lesions of inclusion body myositis (IBM), two populations of T
      cells can morphologically be distinguished, T cells that invade muscle fibers and
      T cells that remain in interstitial areas. Using combined immunohistochemistry
      and RT-PCR, we analysed the TCR expressed by these distinct T cell populations.
      In three of eight IBM muscle specimens, the autoinvasive T cells were stained
      with one of the available mAbs: anti-Vbeta5.3 in patient 1, anti-Vbeta5.2 in
      patient 2, and anti-Vbeta3 in patient 3. The corresponding TCR Vbeta mRNAs were
      amplified by RT-PCR and the PCR products were cloned and sequenced. In all three
      specimens, the TCRs expressed by the autoinvasive T cells were clonally
      restricted. Furthermore, in patient 1 two different mAbs labelled two distinct
      populations of T cells: an autoaggressive population of CD8 + Vbeta5.3 + cells
      that invaded muscle fibers and a noninvasive interstitial population of CD8 -
      Vbeta5.1 + cells. TCR sequence analysis revealed that the noninvasive Vbeta5.1 +
      T cells were clonally diverse, whereas the autoinvasive Vbeta5.3 + T cells were
      clonally restricted.

PMID- 9600713
TI  - Adhesion molecule phenotype of T lymphocytes in inflamed CNS.
AB  - The phenotype of T cells in the central nervous system (CNS) in two models of
      chronic inflammation (experimental allergic encephalomyelitis and Corynebacterium
      parvum-induced inflammation) was compared to that of T cells in gut and
      chronically inflamed subcutaneous tissue and lung. CNS T cells display a similar
      phenotype in both inflammatory models, and are phenotypically unique compared to
      T cells from the other inflamed tissues. T cells from inflamed CNS are mainly
      CD4+ and are the only population examined that express a typical activated/memory
      phenotype: CD44high/LFA-1high/ICAM-1high/CD45RBlow. The CNS T cells are
      alpha4beta7-integrin(negative), but express alpha4-integrin and activated beta1
      integrin, suggesting expression of the alpha4beta1-heterodimer in an activated
      state. In contrast, most T cells in gut express low levels of activated beta1
      integrin. The CNS T cells lack expression of alpha6 and alphaE integrin chains
      and L-selectin. In inflamed CNS and inflamed subcutaneous tissue, approximately
      50% of T cells express high affinity ligands for P-selectin while fewer than 10%
      express high affinity ligands for E-selectin. In summary, our data show that,
      independent of the inflammatory stimulus, T cells recruited into the inflamed CNS
      are phenotypically distinct from T cells in other inflamed tissues. This finding
      leads us to hypothesize the existence of a phenotypically distinct 'CNS-seeking'
      T lymphocyte population.

PMID- 9600714
TI  - Autoimmunity in paraneoplastic neurological disorders.
AB  - Antibodies to neuronal antigens are found in a range of different neurological
      disorders, both central and peripheral, and often indicate the presence of
      particular underlying tumours. This conference and workshop was an opportunity to
      discuss the clinical associations of these antibodies, the relevance of new
      antibody specificities, and to establish protocols for their detection.

PMID- 9600715
TI  - Variability of mitomycin C adsorption by activated charcoal.
AB  - A saline suspension of mitomycin C adsorbed on activated charcoal and
      administered intraperitoneally has been reported to be safe and effective in the
      treatment of gastric carcinoma. Activated charcoal specifically targets tumour
      and lymph-node tissues and the sustained higher local drug concentration is
      thought to be beneficial. The charcoal particles used in these suspensions have
      varied in size from > 147 microm to < 20 nm in diameter, but no data have been
      published to show how this might affect drug adsorption and delivery. Any
      variability in drug adsorption could pose a serious clinical risk for drugs with
      a narrow therapeutic index. We have, therefore, investigated the adsorption of
      mitomycin C on activated charcoal in-vitro. Activated charcoal was ground and
      sieved to yield four size-fractions between 180 and 53 microm. Adsorption
      isotherms (n > or = 3) were constructed and applied to the Freundlich model with
      0-l00 microg mL(-1) mitomycin C measured by HPLC with detection at 365 nm.
      Adsorption of mitomycin C by activated charcoal varied by a factor of three under
      identical conditions at room temperature (21 degrees C) and at 37 degrees C. The
      specific adsorption (microg mitomycin C (mg activated charcoal)(-1)) was
      generally higher at 37 degrees C than at room temperature. The variability of
      mitomycin C adsorption was greatly reduced by addition of the surface-active
      agent polyvinylpyrollidone, used to determine that adsorption of mitomycin C was
      independent of activated charcoal particle size. The characteristics of
      adsorption of mitomycin C by activated charcoal are complex and should be
      thoroughly investigated to discover the critical controlling factors before
      submitting the suspensions for further clinical evaluation.

PMID- 9600716
TI  - Study of the interaction of dithranol with heptakis(2,3,6-tri-O-methyl)-beta
      cyclodextrin in solution and in the solid state.
AB  - The interaction between dithranol and heptakis(2,3,6-tri-O-methyl)-beta
      cyclodextrin (TMBCyD) has been investigated in aqueous solution containing
      isoascorbic acid (0.2% w/v) as antioxidant and in the solid state. The
      interaction in the solid state was studied by differential scanning calorimetry
      (DSC), infrared spectroscopy (IR), X-ray powder diffractometry (XPD) and a
      dissolution-rate method. The extent of complexation between the two substances
      was poor, as indicated by the low value of the slope of the linear part of the
      solubility curve. A phase diagram was constructed by measuring the thermal
      behaviour of various re-solidified physical mixtures of dithranol and of TMBCyD
      previously subjected to heating until melting of the TMBCyD. The loss of
      dithranol, owing to sublimation and degradation caused by the thermal treatment
      used, was less than 10%. In keeping with XPD and IR data, the phase diagram
      indicated that a complex was formed containing 13.7% dithranol (molar ratio 1:1)
      which had a congruent melting point at 164 degrees C. The drug dissolution rate
      from the 1:1 complex was measurable, unlike that of the corresponding physical
      mixture, and was significantly increased when the complex was dispersed in the
      glassy matrix of TMBCyD, as it was in re-solidified mixtures containing 2-7%
      dithranol. The results show that the solubility of dithranol is increased
      significantly as a consequence of its interaction with TMBCyD, despite the low
      extent of complexation between the two substances.

PMID- 9600717
TI  - Kinetic characterization and identification of the enzymes responsible for the
      hepatic biotransformation of adinazolam and N-desmethyladinazolam in man.
AB  - The kinetics of the N-demethylation of adinazolam to N-desmethyladinazolam
      (NDMAD), and of NDMAD to didesmethyladinazolam (DDMAD), were studied with human
      liver microsomes using substrate concentrations in the range 10-1000 microM. The
      specific cytochrome P450 (CYP) isoforms mediating the biotransformations were
      identified using microsomes containing specific recombinant CYP isozymes
      expressed in human lymphoblastoid cells, and by the use of CYP isoform-selective
      chemical inhibitors. Adinazolam was demethylated by human liver microsomes to
      NDMAD, and NDMAD was demethylated to DDMAD; the substrate concentrations, Km, at
      which the reaction velocities were 50% of the maximum were 92 and 259 microM,
      respectively. Another metabolite of yet undetermined identity (U) was also formed
      from NDMAD (Km 498 microM). Adinazolam was demethylated by cDNA-expressed CYP
      2C19 (Km 39 microM) and CYP 3A4 (Km 83 microM); no detectable activity was
      observed for CYPs 1A2, 2C9, 2D6 and 2E1. Ketoconazole, a relatively specific CYP
      3A4 inhibitor, inhibited the reaction; the concentration resulting in 50% of
      maximum inhibition, IC50, was 0.15 microM and the inhibition constant, Ki, was <
      0.04 microM in five of six livers tested. Troleandomycin, a specific inhibitor of
      CYP 3A4, inhibited adinazolam N-demethylation with an IC50 of 1.96 microM. The
      CYP 2C19-inhibitor omeprazole resulted in only partial inhibition (IC50 21
      microM) and sulphaphenazole, alpha-naphthoflavone, quinidine and
      diethyldithiocarbamate did not inhibit the reaction. NDMAD was demethylated by
      cDNA-expressed CYP 3A4 (Km 220 microM, Hill number A 1.21), CYP 2C19 (Km 187
      microM, Hill number A 1.29) and CYP 2C9 (Km 1068 microM). Formation of U was
      catalysed by CYP 3A4 alone. Ketoconazole strongly inhibited NDMAD demethylation
      (IC50 0.14 microM) and formation of U (IC50 < 0.1 microM) whereas omeprazole and
      sulphaphenazole had no effect on reaction rates. These results show that CYP 3A4
      is the primary hepatic CYP isoform mediating the N-demethylation of adinazolam
      and NDMAD. Co-administration of adinazolam with CYP 3A4 inhibitors such as
      ketoconazole or erythromycin might lead to reduced efficacy, since adinazolam by
      itself has relatively weak benzodiazepine agonist activity, with much of the
      pharmacological activity of adinazolam being attributable to its active
      metabolite NDMAD.

PMID- 9600718
TI  - Pharmacokinetic assessment of the sites of first-pass metabolism of BMS-181101,
      an antidepressant agent, in rats.
AB  - The relative contribution of the gut and the liver to the first-pass metabolism
      of BMS-181101 (3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-5-fluoro
      1H-ind ole dihydrochloride), a potential antidepressant agent, has been evaluated
      in rats. Nine male Sprague-Dawley rats were divided into three groups of three
      and each rat received a single 20 mg kg(-1) dose of [14C]BMS-181101 via a 30 min
      constant-rate intravenous infusion, a 30-min constant-rate intraportal infusion
      or oral gavage. Serial blood samples were collected for 8 h after dosing and
      plasma was analysed for unchanged BMS-181101 and total radioactivity. Extraction
      ratios for BMS-181101 by the gut and liver were calculated on the basis of ratios
      of the area under the plasma BMS-181101 concentration-time curve. The gut had a
      high intrinsic capacity for metabolizing BMS-181101-extraction ratios were 93%
      and 10% for the gut and liver, respectively. After oral administration BMS-181101
      is sequentially exposed to the gut then the liver. As a result, the contribution
      of the gut to the overall first-pass effect (ca. 93%) was significantly greater
      than that of the liver (ca. 0.7%). The estimated total first-pass effect of 94%
      for BMS-181101 in rats is in excellent agreement with the observed absolute oral
      bioavailability of 6%. These results clearly illustrate the importance of
      metabolic activity in the gut for orally administered BMS-181101.

PMID- 9600719
TI  - Distribution of bismuth in the rat after oral dosing with ranitidine bismuth
      citrate and bismuth subcitrate.
AB  - Bismuth preparations are used world-wide for the management of peptic ulcer
      disease, for eradication of Helicobacter pylori, and in the prevention and
      treatment of diarrhoea. However neurological toxicity of bismuth has always been
      a major concern and evidence has been found of the absorption of bismuth. Recent
      studies have suggested that the absorption of bismuth increases when bismuth
      salts are used with ranitidine hydrochloride. The absorption and deposition of
      bismuth as a result of the use of the new drug ranitidine bismuth citrate have
      not been yet clarified. After 15 days of twice daily oral gavage with bismuth
      subcitrate, 13.7 mg kg(-1) day(-1) to eight rats, deposition of bismuth was found
      in all the tissues studied, especially the kidney (30.81 +/- 8.59 microg g(-1)
      dry weight). A similar pattern of distribution and tissue concentrations was
      found when bismuth subcitrate was given with ranitidine hydrochloride 8.6 mg kg(
      1) day(-1) to another eight rats, although this combination resulted in lower
      brain levels (3.12 + 1.31 microg g(-1) dry weight) than after administration of
      bismuth subcitrate alone (4.77 +/- 0.97 microg g(-1) dry weight). When six rats
      were given ranitidine bismuth citrate by gavage at 22.8 mg kg(-1) day(-1) for 15
      days, kidney levels were lower (4.24 +/- 1.75 microg g(-1) dry weight) and brain
      levels were below detection limits; the bismuth concentrations in the faeces from
      this group were also significantly lower (1603 +/- 104.0 microg g(-1) dry weight)
      than for the two other groups. After dosing with bismuth alone or in association
      with ranitidine hydrochloride, bismuth was detected in several organs and
      deposition was not influenced by gastric pH. Blood levels correlate poorly with
      organ deposition and brain deposition was not always associated with
      encephalopathy. After administration of ranitidine bismuth citrate, significantly
      lower concentrations of bismuth were found in the kidney and bismuth was not
      detectable in the brain, suggesting lower bismuth absorption. This was confirmed
      by higher levels in the faeces after dosing with ranitidine bismuth citrate.
      Thirty days after dosing with ranitidine bismuth citrate or bismuth subcitrate,
      bismuth could not be detected in any of the organs examined but could be found in
      the urine. In conclusion, bismuth was deposited in the kidney, brain, lung and
      liver of rats after oral dosing with bismuth subcitrate. After oral dosing with
      an equivalent amount of bismuth in the form of ranitidine bismuth citrate,
      significantly lower concentrations of bismuth were deposited in the kidney; in
      the brain bismuth was not detectable.

PMID- 9600720
TI  - Study of the effects of dispase in the chemotherapy of multicellular tumour
      spheroids of small-cell lung carcinoma in man.
AB  - Multicellular tumour spheroids (MTS), diameter 650 microm, from PC-6, SBC-1 and
      NCL-H60 small-cell lung carcinoma cell-lines in man were prepared by the liquid
      overlay culture method and used to study the influence of treatment with dispase
      (bacterial neutral protease from Bacillus polymyxa, 1000 units mL(-1)) on the
      effectiveness of carboplatin, as determined by colony-forming assay. When
      carboplatin alone was used on monolayers the curve of survival fraction against
      concentration was exponential in shape, indicating that the drug was active
      against the monolayer. When MTS were treated with medium concentrations (10(-5)
      and 10(-4) M) of carboplatin alone the survival fraction-concentration curve
      showed that the effectiveness of the treatment was less than that against the
      monolayer. On treatment of MTS with carboplatin and dispase the survival fraction
      concentration curve was similar to that obtained for the monolayer and the
      survival fraction of the core of the MTS was also less than when carboplatin
      alone was used. These results imply that dispase dissolves the intercellular
      matrix of the MTS enabling enhanced infiltration of carboplatin into the core of
      the MTS. Dispase thus indirectly increases the effectiveness of carboplatin.

PMID- 9600721
TI  - HPLC on Chiralcel OJ-R for enantiomer separation and analysis of ketoprofen, from
      horse plasma, as the 9-aminophenanthrene derivative.
AB  - Racemic ketoprofen is a non-steroidal anti-inflammatory drug used to treat
      musculoskeletal and colic conditions in horses. The enantioselective chiral
      inversion of ketoprofen administered to horses has been studied by use of
      cellulose tris(4-methylbenzoate), also known as Chiralcel OJ-R, as chiral
      stationary phase; acetonitrile - 0.02 M perchlorate buffer (pH 2.0)-methanol,
      60:15:25 (v/v/v) was used as mobile phase. Before chromatography, to effect
      adequate chiral interaction with the chiral stationary phase ketoprofen was
      derivatized with 9-aminophenanthrene, under acid conditions, after solid-phase
      (C18) extraction and then liquid-liquid extraction, to ensure effective removal
      of endogenous plasma materials. The 9-aminophenanthrene derivative of S-ibuprofen
      was used as internal standard. The enantiomers of ketoprofen were separated to
      baseline (Rs = 6.44, alpha = 1.76) within a short analysis time. The results
      indicate that the bio-inversion of R-ketoprofen to the S isomer is significant in
      equine species. However, considerable differences in pharmacokinetic parameters
      were observed, indicating large inter-animal variation.

PMID- 9600722
TI  - Influence of new fenpropimorph fungicides on the growth and sterol composition in
      Saccharomyces cerevisiae: relationship between structure and activity.
AB  - The toxicity of fenpropimorph and seven newly synthesized analogues against
      Saccharomyces cerevisiae has been determined in liquid media. The inhibitory
      effect of the most efficient derivative is 120 times more than that of standard
      fenpropimorph. The non-linear relationship between hydrophobicity and toxicity
      indicates that the binding of the compounds to the receptors does not differ and
      so the differences in toxicity reflect changes in the rate of metabolism. The
      presence of inhibitors in the fermentation medium resulted in a reduction in
      harvested biomass and lipid yield, and changes in sterol composition -- the
      amount of ergosterol decreased whereas the amounts of lanosterol,
      dihydroergosterol and squalene increased. The toxicity of the compounds was most
      influenced by their lipophilicity. Use of this information could lead to
      development of more potent ergosterol inhibitors.

PMID- 9600723
TI  - Importance of initial environments in the development of ambulatory sensitization
      to methamphetamine and cocaine in mice.
AB  - Repeated administration of CNS stimulants such as amphetamines and cocaine
      induces behavioural sensitization which can be influenced by the animal's
      environment. This study has evaluated the effect of restraint on the development
      and maintenance of ambulatory sensitization to methamphetamine and cocaine in
      mice. Subcutaneous administration of the CNS stimulants methamphetamine (2 mg kg(
      1)) and cocaine (20 mg kg(-1)) seven times at three-day intervals resulted in
      ambulatory sensitization when the mice were placed in 20-cm diameter activity
      cages after each dose of the drug. However, if methamphetamine or cocaine was
      administered when the mice were in small jars (6-cm diameter) in which expression
      of ambulation, but not of circling and rearing, was completely restricted, the
      development of ambulatory sensitization was retarded or inhibited, with circling
      behaviour concurrently increased, when subsequent repeated doses of the drug were
      administered in the activity cage. Subsequent repeated treatment of ambulatory
      sensitized mice with the drug or saline when the mice were in the jars did not
      change the levels of the ambulatory sensitization or the circling behaviour.
      These results suggest that the mice are sensitized to the behavioural effect of
      CNS stimulants which can be expressed in the environment in which the drug is
      administered. It is also considered that the established sensitization is
      strongly retained and is responsible for retardation or suppression of the
      development of sensitization to other behavioural stimulant effects.

PMID- 9600724
TI  - Effect of Mn2+ on the development of tension induced in guinea-pig taenia coli by
      Bay K 8644.
AB  - We have studied the effects of Mn2+ on the contractile response induced by Bay K
      8644, a dihydropyridine Ca2+ agonist, on guinea-pig taenia coli. Mn2+ (5 mM)
      completely inhibited Bay K 8644 (10(-6) M)-induced rhythmic contraction and
      contracture to baseline values in normal Ca2+ medium; thereafter, the contraction
      progressively increased to about 90% of the K+ (60 mM)-induced tonic response. In
      Ca2+-free medium in the presence of Bay K 8644 Mn2+ also evoked contraction and a
      concomitant increase in Mn2+ influx into the cytoplasm. These results suggest
      that during the opening of voltage-dependent Ca2+ channels activated by Bay K
      8644, Mn2+ can enter cytoplasm through the channels and induce contraction in
      taenia coli.

PMID- 9600726
TI  - The non-peptide neuroprotective agents SR 57746A interacts with neurotrophin 3 to
      induce differentiation in the PC12 cell-line.
AB  - SR 57746A (1-(2beta-naphthylethyl)-4-(3-trifluoromethylphenyl)-1,2,5,6 
      tetrahydropyridine hydrochloride) is a neuroprotective compound which potentiates
      nerve-growth factor (NGF)-induced differentiation in PC12 cells. We have
      evaluated the interaction of SR 57746A with the other members of the neurotrophin
      family in this cell-line. In contrast with NGF, neurotrophin-3 did not increase
      the differentiation of PC12 cells. However, the association of SR 57746A with
      neurotrophin-3 significantly increased neurite outgrowth. No significant activity
      on neurite outgrowth was observed with brain-derived neurotrophic factor or
      neurotrophin-4, either alone or combined with SR 57746A. These results indicate
      that as well as potentiating the effect of NGF SR 57746A enables neurotrophin-3,
      which alone is inactive, to increase the differentiation of these cells.

PMID- 9600725
TI  - The 5-HT and alpha-adrenoceptor antagonist effect of four benzylisoquinoline
      alkaloids on rat aorta.
AB  - The action of four benzylisoquinoline alkaloids (two aporphines-glaucine and
      apomorphine, a benzylisoquinoline-papaverine and a
      bisbenzyltetrahydroisoquinoline-antioquine) on 5-HT-induced contraction in rat
      thoracic aorta has been examined and compared with that of the control drugs:
      ketanserin, nifedipine, prazosin and phentolamine. The relaxant action on 5-HT
      induced contraction was contrasted with that on the contraction induced by
      noradrenaline and KCl. The results obtained with control drugs show that
      ketanserin has clear selectivity for 5-HT receptors, whereas prazosin and
      phentolamine have high selectivity for the alpha1-adrenoceptor and nifedipine
      seems to have a more potent effect on KCl-induced contraction than on that
      induced by 5-HT or noradrenaline. The contraction evoked by 5-HT (10 microM) was
      inhibited in a concentration-dependent manner by all the alkaloids. The order of
      potency was: papaverine = glaucine > apomorphine > antioquine. Papaverine had a
      non-specific relaxant action on 5-HT-, noradrenaline- and KCl-induced
      contraction, antioquine had a weak relaxant action on the agonist assays, and
      glaucine and apomorphine inhibited noradrenaline- and 5-HT-induced contraction
      more potently than they inhibited the K+-depolarized response. These results
      indicate that the aporphines assayed, S-glaucine and R-aporphine, had selective
      action against agonist (noradrenaline or 5-HT)-induced contraction rather than
      against KCl-depolarization of rat aorta. In contrast papaverine, a
      benzylisoquinoline alkaloid, relaxes all agents used non-selectively as could be
      expected from the lack of specificity that characterizes this alkaloid.

PMID- 9600727
TI  - In-vitro negative chronotropic and inotropic effects of a novel dihydropyridine
      derivative, CD-832, in the guinea-pig: comparison with calcium-channel
      antagonists.
AB  - The effects of CD-832 (4R-(-)-2-(nicotinoylamino)ethyl-3-nitroxypropyl-1,4
      dihydro -2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate) , a novel
      dihydropyridine derivative, on guinea-pig isolated myocardial preparations have
      been compared with those of Ca2+-channel antagonists. All ten compounds induced
      concentration-dependent negative chronotropic effects on preparations of isolated
      right atria and negative inotropic effects on isolated right ventricular
      papillary muscles. The order of potency for the negative chronotropic effect was
      CD-832 > nicardipine = gallopamil > clentiazem > nifedipine = efonidipine >
      amlodipine = semotiadil > verapamil > diltiazem; that for the negative inotropic
      effect was nicardipine = gallopamil > nifedipine > verapamil > CD-832 > diltiazem
      > clentiazem > efonidipine = semotiadil > amlodipine. The ratio of the EC50 (the
      concentration of Ca2+ antagonist having 50% of the maximum effect) for the
      negative inotropic effect divided by the EC50 for the negative chronotropic
      effect, considered to be an index of selectivity for negative chronotropic
      effect, was higher for CD-832, amlodipine, efonidipine and semotiadil than for
      the other Ca2+ antagonists. The ratio for CD-832, nifedipine, nicardipine,
      efonidipine, amlodipine, verapamil, gallopamil, diltiazem, clentiazem and
      semotiadil was 11.4, 0.29, 0.87, 35.4, 37.1, 0.65, 0.87, 0.92, 7.11 and 30.0,
      respectively. These findings indicate that CD-832 and the newly developed Ca2+
      antagonists including amlodipine, efonidipine, semotiadil and clentiazem were
      selective for a negative chronotropic effect rather than for a negative inotropic
      effect. This 'chrono-selective' effect of these drugs might be of benefit in the
      treatment of cardiovascular disorders.

PMID- 9600728
TI  - Interaction between substance P and beta-adrenergic agonists in the modulation of
      the secretion of fluid and protein by the rat submandibular gland.
AB  - The interactions between substance P and beta-adrenergic agonists such as
      isoprenaline, dobutamine and terbutaline in the control of the secretion of fluid
      and protein from the rat submandibular gland have been examined. Substance P
      elicited large volumes of saliva whereas isoprenaline, dobutamine and terbutaline
      elicited small volumes only. The secretion of fluid in response to substance P
      was markedly enhanced when substance P was administered in combination with
      isoprenaline or dobutamine but not when it was administered in combination with
      terbutaline. Isoprenaline elicited large amounts of protein, whereas substance P
      elicited small amounts. The secretion of protein in response to isoprenaline did
      not change when isoprenaline was administered in combination with substance P.
      The secretion of fluid and protein induced by substance P in combination with
      isoprenaline was antagonized by metoprolol and by spantide, but it was unaffected
      by pretreatment with ICI118551. These results suggest that in the rat
      submandibular gland stimulation of beta1-adrenoceptors but not of beta2
      adrenoceptors potentiates the secretion of fluid that is induced by stimulation
      of tachykinin receptors, whereas stimulation of tachykinin receptors does not
      enhance the secretion of protein that is induced by stimulation of beta1
      adrenoceptors.

PMID- 9600729
TI  - Effect of the number of samples on Bayesian and non-linear least-squares
      individualization: a study of cyclosporin treatment of haematological patients
      with multidrug resistance.
AB  - We have studied whether the prediction of drug concentrations improves as the
      number of samples used for individualization is increased, and whether the
      Bayesian method of individualization is superior to the non-linear least-squares
      method. Data were obtained from ten adult haematological patients with multidrug
      resistance who were treated with cyclosporin. The predictions of blood
      cyclosporin concentrations were made using the Abbott PKS program. The number of
      samples used for individualization was increased from 1 to 30 for the Bayesian
      method and from 4 to 30 for the non-linear least-squares method. Linear
      regression, percentage prediction error, and absolute and relative predictive
      performance were used to evaluate the predictions. The results show that the
      Bayesian method affords greater precision than the non-linear least-squares
      method, but that the non-linear least-squares method is more accurate and results
      in less bias. Whereas for linear regression predictions improve as the number of
      samples is increased, other evaluations show improvement in the range from 5 to
      11 samples; linear regression, percentage prediction errors and prediction bias
      support the opinion that the Bayesian method progressively becomes the non-linear
      least-squares method as the number of samples used for individualization is
      increased, but the accuracy and precision of prediction do not support this
      opinion. The study supports the statement that Bayes' law requires parameters
      from an infinite population, otherwise the advantage of the Bayesian method might
      be marginal.

PMID- 9600730
TI  - Shenjincao (Palhinhaea cernua) injection for treatment of experimental silicosis
      of rats.
AB  - Shenjincao injection is a traditional Chinese medicine prepared from Palhinhaea
      cernua (L.) A. Franco et Vasc. by ultrafiltration. Its anti-silicosis action has
      been investigated both as a prophylactic and for treatment of the disease. Wistar
      rats were injected intra-tracheally with quartz dust and then divided randomly
      into groups-treatment and control prophylactic groups and treatment and control
      disease groups. After five days or eight weeks, respectively, the silica-exposed
      rats of the two treatment groups were injected intraperitoneally three times a
      week with shenjincao injection, dose 2.0 mL, for five weeks or 11 weeks,
      respectively. The rats were then dissected, and the ceruloplasmin content of the
      serum and the fresh weight, dry weight, collagen content and pathological grade
      of the lungs were measured. Compared with the corresponding exposed control
      groups for the same treatment periods the values of these parameters were reduced
      by 62.8% to 30.7% for rats in the prophylactic treatment group (P < 0.01 for all)
      and by 50.8% to 30.2% for the diseased group (P < 0.01 for all). The values for
      the disease-treatment group were also reduced by 37.9% to 25.9% compared with
      values for the exposed control group before treatment (P < 0.01 or P < 0.05). The
      effective coefficients for prophylactic treatment were 82.6% to 56.0%; for
      disease treatment they were 68.8% to 39.8%. These results show that shenjincao
      injection is efficacious against experimental silicosis not only when used
      prophylactically but also when used to treat the disease.

PMID- 9600731
TI  - Partial trisomy 1q with growth hormone deficiency and normal intelligence.
AB  - We present two sibs with partial trisomy 1 (q31.1-q32.1) due to a familial
      insertion. Patient 1 is a girl who presented at age 9 months with minor
      anomalies, short stature, and normal psychomotor development. Karyotype was
      46,XX,der(4)ins(4;1) (p14;q31.1q32.1)pat. The father had a balanced inverted
      insertion of 1q into 4p, with karyotype 46,XY,ins(4;1)(p14;q31.1q32.1). At age 5
      years, patient 1 was found to have short stature with documented growth hormone
      deficiency and ectopic pituitary. Her growth velocity responded well to treatment
      with growth hormone. Cognitive testing at 5 9/12 years showed normal intelligence
      with an IQ of 90. Patient 2, the brother of patient 1, presented with
      intrauterine growth retardation. He has the same chromosomal insertion as his
      sister, with partial trisomy 1q. We suggest that there is a recognizable
      phenotype of trisomy 1(q31.1-q32.1) which includes prenatal and postnatal growth
      retardation, narrow palpebral fissures, microphthalmia, microstomia, pituitary
      abnormalities, and normal intelligence in some individuals.

PMID- 9600732
TI  - Pseudohypoparathyroidism type Ia from maternal but not paternal transmission of a
      Gsalpha gene mutation.
AB  - While loss-of-function mutations in Gsalpha are invariably associated with the
      short stature and brachydactyly of Albright hereditary osteodystrophy (AHO), the
      association with hormone resistance (to parathyroid hormone and thyrotropin)
      typical of pseudohypoparathyroidism type Ia (PHP-Ia) is much more variable.
      Observational studies and DNA polymorphism analysis suggest that maternal
      transmission of the Gsalpha mutation may be required for full expression of
      clinical hormone resistance. To test this hypothesis, we studied transmission of
      a frameshift mutation in Gsalpha through three generations of a pedigree affected
      by AHO and PHP-Ia. While all family members carrying this loss-of-function
      mutation in one Gsalpha allele had AHO, neither the presence of the mutation nor
      the degree of reduction of erythrocyte Gsalpha bioactivity allowed prediction of
      phenotype (AHO alone versus AHO and PHP-Ia). Paternal transmission of the
      mutation (from the patriarch of the first generation to three members of the
      second generation) was not associated with concurrent PHP-Ia, but maternal
      transmission (from two women in the second generation to four children in the
      third generation) was invariably associated with PHP-Ia. No expansion of an
      upstream short CCG nucleotide repeat region was detected, nor was there evidence
      of uniparental disomy by polymorphism analysis. This report, the first to
      document the effects across three generations of both paternal and maternal
      transmission of a specific Gsalpha mutation, strongly supports the hypothesis
      that a maternal factor determines full expression of Gsalpha dysfunction as PHP
      Ia.

PMID- 9600733
TI  - Direct duplication of 9p22-->p24 in a child with duplication 9p syndrome.
AB  - A de novo direct duplication of 9p22-->p24 was shown in a child with a
      duplication 9p phenotype by GTG banding and fluorescence in situ hybridization
      (FISH) using a chromosome-9 specific painting probe as well as 6 YAC DNA probes
      localized to the 9p13-9p23 region. The breakpoints in this patient and previously
      reported patients suggest that 9p22 may be the critical region for duplication 9p
      syndrome.

PMID- 9600734
TI  - Pacman dysplasia: report of two affected sibs.
AB  - We report on two sib fetuses with radiological and morphological findings similar
      to those of the recently described lethal skeletal dysplasia termed Pacman
      dysplasia (McKusick, 167220, Am J Med Genet 1993, 45:558-561). The first fetus, a
      male, was electively terminated after a routine ultrasound study at 20 weeks
      showed short-limb dwarfism. The second fetus, a female sib, was also electively
      terminated after similar, abnormal ultrasound findings were noted at 16 weeks of
      gestation. Similar to Pacman dysplasia, the radiographic appearance was
      characterized by under-mineralized bone, stippling, rhizomelic and mesomelic
      shortness, platyspondyly, and a short, broad pelvis. The metaphyses were dense,
      but the diaphyseal cortices were thin with undermodeled long bones, and there was
      a deficient trabecular pattern suggesting marrow replacement. Chondro-osseous
      structure was characterized by deficient trabecular bone formation, a fibrous
      marrow, and numerous, large, multinucleated osteoclasts lining the endosteal
      surfaces of the metaphyseal bone. The occurrence of this dysplasia in sibs of
      differing sex suggests autosomal recessive inheritance.

PMID- 9600735
TI  - Familial laryngeal paralysis.
AB  - Vocal fold paralysis (VFP) is the second most frequent cause of congenital
      stridor. Although often due to birth trauma, infection, and brainstem
      abnormalities, most cases are idiopathic. Infrequently, a family history of VFP
      is elicited, identifying a role for genetic factors in laryngeal function. This
      study describes a family in which an autosomal dominant form of familial
      laryngeal abductor paralysis segregates. The typical physical findings,
      diagnostic and therapeutic considerations, and possible molecular mechanisms of
      this disorder are discussed in detail.

PMID- 9600736
TI  - Renal cell carcinoma with X;1 translocation in a child with Klinefelter syndrome.
AB  - Klinefelter syndrome (KS) is a sex chromosome abnormality occurring in 1 in 1,000
      males. An association with leukemia, germ cell tumor, and male breast cancer has
      been suggested in KS. Such information is important for professionals caring for
      KS patients as the condition is frequently not clinically recognizable until
      after puberty. We report on a renal cell carcinoma (RCC) in a 10-year-old boy
      with KS. He developed intermittent hematuria at age 10 years and was diagnosed
      with a right kidney mass, which on pathology was identified as RCC. In addition,
      he was known to have learning disabilities and language delays. Analysis of
      peripheral blood chromosomes showed a 47,XXY karyotype while analysis of tumor
      cells demonstrated clonal abnormalities including a translocation between
      chromosomes X and 1, designated
      47,XXYc,t(X;1)(p11.2;q21)[6]/47,XXYc,t(X;1),r(Xp)[2]/46,X XYc,-X,t(X;1)[7]. Renal
      cell carcinoma is rare in childhood and is not previously reported in KS. The
      oncogenetic significance of the chromosomal regions involved in this
      translocation is discussed in relation to the congenital abnormality of the
      patient.

PMID- 9600737
TI  - Retinoblastoma and Hirschsprung disease in a patient with interstitial deletion
      of chromosome 13.
AB  - Retinoblastoma is a rare pediatric malignancy (1/20,000) while Hirschsprung
      disease is a relatively common pediatric disorder (1/5,000). We describe a boy
      with bilateral retinoblastoma, Hirschsprung disease, multiple minor anomalies,
      and an interstitial deletion 13q (q13 --> q22). This child and a similar
      previously reported girl with retinoblastoma and Hirschsprung disease may
      represent a previously unrecognized contiguous gene syndrome.

PMID- 9600738
TI  - Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to
      chromosome 9.
AB  - The neuronal ceroid lipofuscinoses (NCLs) comprise a set of at least 6 distinct
      human and an unknown number of animal diseases characterized by storage of
      proteolipids in lysosomes of many cell types. By unknown mechanisms, this
      accumulation leads to or is associated with severe neuronal and retinal
      degeneration. The genes for 3 human NCLs, infantile, late infantile, and
      juvenile, have been cloned. The first murine form of NCL, the motor neuron
      degeneration (mnd) mouse, has been described and mapped to proximal Chromosome 8.
      Here we describe a second genetic variant of NCL in the mouse, neuronal ceroid
      lipofuscinosis, nclf. These mice exhibited a phenotype that was almost exactly
      the same as that observed in mnd/mnd mice. Homozygous nclf mice developed
      progressive retinal atrophy early in life and become paralyzed at around 9 months
      of age. They accumulated luxol fast blue staining material in cytoplasm of
      neurons and many other cell types. Ultrastructurally, affected lysosomes had a
      "finger print pattern" with membranous material arranged in "pentalaminar"
      patterns. Affected mice developed severe cerebral gliosis in late stages of their
      disease. They also had severe Wallerian degeneration of long tracts in spinal
      cord and brain stem, lesions that accounted for the distinctive upper motor
      neuron signs displayed by both nclf/nclf and mnd/mnd mice. By crossing nclf/nclf
      mice with CAST/Ei mice, linkage analysis of nclf with respect to SSLP markers was
      performed, showing that nclf is located on Chromosome 9 between D9Mit164 and
      D9Mit165, in a region that is homologous with human Ch 15q21, where the gene for
      one variant of late infantile NCL, CLN6, recently has been mapped. The genes for
      two proteolipids known to be stored in lysosomes of animals and people with NCL
      were also mapped in this study and found not to map to the mnd or nclf loci nor
      to any mouse locus homologous to any known human NCL disease locus.

PMID- 9600740
TI  - A 5-year-old girl with interstitial deletion of 3p14: clinical, psychologic,
      cytogenetic, and molecular studies.
AB  - An interstitial deletion of segment 3p14 (breakpoints 3p21.1 and 3p13) was found
      in a 5-year-old short, microcephalic, and mentally retarded girl with a pattern
      of anomalies comprising a wide forehead, short up-slanting palpebral fissures,
      small nose and ears, hypoplasia of larynx, trachea, and bronchi, clino- and
      camptodactyly of little fingers, and sacral vertebral fusion. Determination of
      microsatellites mapping to the deleted segment demonstrated that the deletion had
      occurred in the paternal germ line. This is the seventh patient with a deletion
      of 3p14, and comparison with the six previously reported cases does not yet allow
      definition of a specific pattern of minor and major anomalies.

PMID- 9600739
TI  - De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia.
AB  - With the recent report of mutations in the calcium channel gene CACNA1A in two
      families with episodic ataxia type 2, we investigated a patient with nonfamilial
      episodic vertigo and ataxia responsive to acetazolamide for similar mutations.
      Single-strand conformation polymorphism (SSCP) analysis of exon 23 identified an
      extra band in the patient that was not present in other relatives or in normal
      controls. Exon 23 of the patient showed a spontaneous C to T substitution at
      position 4410 resulting in an early stop codon. Patients with nonfamilial
      episodic ataxia may respond to acetazolamide and may have mutations in CACNA1A.

PMID- 9600741
TI  - Multiple congenital anomalies in a fetus with 45,X/46,X,r(X)(p11.22q12)
      mosaicism.
AB  - Ring X chromosomes that do not undergo inactivation may cause malformations and
      mental retardation. We report on a fetus with anencephaly, total dorsal
      rachischisis, and diaphragmatic hernia that was found to have a mosaic
      45,X/46,X,r(X)(p11.22q12) karyotype. Fluorescent in situ hybridization (FISH)
      confirmed that the ring chromosome was X-derived. This report expands the
      phenotypic spectrum of mosaic monosomy X and small ring X chromosomes.

PMID- 9600742
TI  - Prenatal diagnosis of Fukuyama type congenital muscular dystrophy in eight
      Japanese families by haplotype analysis using new markers closest to the gene.
AB  - We conducted prenatal diagnosis by haplotype analysis, using newly developed
      microsatellite markers, in eight Fukuyama type congenital muscular dystrophy
      (FCMD) families. In addition to six new families, two previously reported
      families were reexamined by haplotype analysis including detection of an
      ancestral founder haplotype (138-183-301) for 3 microsatellite markers closest to
      the FCMD gene, designated D9S2105-D9S2107-D9S172, the distances of which from the
      FCMD gene are presumed to be approximately 140, approximately 20, and
      approximately 280 kb, respectively. Five fetuses from five families were
      diagnosed as nonaffected, and were subsequently confirmed to be healthy. Three
      fetuses of the other three families were diagnosed as having a high probability
      of being affected by FCMD. In the prenatal diagnosis conducted for these eight
      families, the ancestral founder allele was observed in 13 of 16 (81%) FCMD
      bearing chromosomes. Detection of the ancestral haplotype facilitated achieving
      accurate prenatal diagnosis of FCMD. The brains of all three fetuses prenatally
      diagnosed as FCMD-affected showed the initial stage of cortical dysplasia, strong
      evidence of FCMD.

PMID- 9600743
TI  - Prenatally diagnosed neural tube defects: ultrasound, chromosome, and autopsy or
      postnatal findings in 212 cases.
AB  - From January 1990 until December 1996, 212 cases of neural tube defect (NTD) were
      seen through the Prenatal Diagnosis Program of the University of Toronto. Of the
      212 cases, 200 were karyotyped successfully and of these, 13 (6.5%) had
      chromosome abnormalities. When classified according to the site of the NTD, 2.3%
      (2/88) of anencephalics, 7.1% (1/14) of encephaloceles, and 10.2% (10/98) of
      meningomyeloceles had abnormal karyotypes. The absence of associated ultrasound
      abnormalities was not necessarily predictive of a chromosomally normal fetus;
      4/167 (2.4%) of fetuses with isolated NTDs had chromosome abnormalities.
      Conversely, 24/33 (72%) of fetuses with additional findings on ultrasound had
      normal chromosomes. The diagnosis of a chromosome abnormality associated with NTD
      has important implications for recurrence risk and prenatal diagnosis, not only
      for the parents but potentially for other relatives. Based on our finding that
      6.5% of prenatally detected NTDs are associated with chromosome abnormalities, we
      recommend karyotyping of all fetuses and/or newborns with NTD.

PMID- 9600744
TI  - Syndrome of coronal craniosynostosis with brachydactyly and carpal/tarsal
      coalition due to Pro250Arg mutation in FGFR3 gene.
AB  - Recently, a unique Pro250Arg point mutation in fibroblast growth factor receptor
      3 (FGFR3) was reported in 61 individuals with coronal craniosynostosis from 20
      unrelated families [Muenke et al. (1997): Am J Hum Genet 60:555-564]. The
      discovery of this apparently common mutation has resulted in the definition of a
      recognizable syndrome, through analysis of subtle clinical findings in families
      who were previously thought to have a variety of other craniosynostosis
      syndromes. Previous diagnoses in some of these families have included Jackson
      Weiss, Saethre-Chotzen, and Pfeiffer syndromes, as well as Adelaide-type
      craniosynostosis and brachydactyly-craniosynostosis syndrome [Ades et al. (1994):
      Am J Med Genet 51:121-130; von Gernet et al. (1996): Am J Med Genet 63:177-184;
      Reardon et al. (1997): J Med Genet 34:632-636; Bellus et al. (1996): Nat Genet
      14:174-176; Hollaway et al. (1995): Hum Mol Genet 4:681-683; Glass et al. (1994):
      Clin Dysmorphol 3:215-223]. There appears to be a need to further delineate the
      phenotype associated with this common mutation in FGFR3. We compare the clinical
      characteristics of previously reported cases of this unique Pro250Arg mutation
      with those of two additional families and suggest that this syndrome with a
      unique mutational basis be designated coronal craniosynostosis with brachydactyly
      and carpal/tarsal coalition due to Pro250Arg mutation in FGFR3 gene, to emphasize
      the distinctive findings which may be present even in the absence of coronal
      craniosynostosis.

PMID- 9600745
TI  - Townes-Brocks and Pendred syndrome in the same patient.

PMID- 9600746
TI  - Congenital heart disease in Robinow syndrome.

PMID- 9600747
TI  - Diastrophic dysplasia diagnosed in a case published 100 years ago.

PMID- 9600748
TI  - Renal and retinal involvement in the Sensenbrenner syndrome.

PMID- 9600757
TI  - Lessons from the space experiment SL-J/FMPT/L7: the effect of microgravity on
      chicken embryogenesis and bone formation.
AB  - Thirty fertilized chicken eggs preincubated for 0, 7, and 10 days on earth (10
      eggs each) were flown in the space shuttle "Endeavour" and further incubated for
      7 days under microgravity. Twenty out of 30 eggs (nine out of ten 10-day-old
      eggs; 10 out of ten 7-day-old eggs; 1 out of ten 0-day-old eggs) were recovered
      alive after landing. The only living embryo of the 0-day-old egg died 24 days
      after launch, and was comparable to a 16-day-old embryo when it died. The high
      mortality of the 0-day-old eggs appeared to be related to the specific inner
      structure of the egg. The yolk (specific gravity, 1.029) would not have separated
      from the albumen (1.040) during space flight. The subtle difference in specific
      gravity between the yolk and the albumen appeared to play a critical role in
      early chick embryogenesis. All the tissues, including cartilage and bone, were
      formed normally in 7- and 10-day-old chicken embryos during space flight. When
      the 7- and 10-day-old embryos recovered at Kennedy Space Center (KSC) were
      further incubated on earth, they hatched normally. No appreciable changes were
      recognized in these chicks. The reason for these unexpected results is not known.
      Further space experiments are needed to explain the failure of the effects of
      microgravity on chicken embryogenesis.

PMID- 9600758
TI  - Medical baseline data collection on bone and muscle change with space flight.
AB  - It has been documented that astronauts suffer from a progressive and continuous
      negative calcium balance in space flight. The National Space Development Agency
      of Japan (NASDA) discussed the experimental protocols with the National
      Aeronautics and Space Agency's (NASA's) Johnson Space Center (JSC) and has
      started a medical baseline collection on bone and calcium metabolism, and muscle
      changes with space flight. The subjects were two astronauts, a 42-year-old female
      and a 32-year-old male, who experienced real space flights. Fractional excretion
      of calcium (FECa) increased in both subjects just after the space flight. There
      was a negative calcium balance with urinary calcium leak even after a short
      flight. We also noticed a decrease (-3.0%) of bone mineral density (BMD) of the
      lumbar spine (L2-4), a weight bearing bone. These bone changes may be due to a
      negative calcium balance. However, the BMD of the skull, a nonweight bearing
      bone, increased after the flight. This indicates that the effect of
      weightlessness on bone is different in respective bones, depending on the weight
      loading. Our data of the bone metabolic marker clearly indicate that bone
      resorption is stimulated, shown by an elevation of urinary pyridinolinks and
      plasma tartrate-resistant acid phosphate (TRACP) activity. Bone specific alkaline
      phosphatase, a bone formation marker, was elevated in both subjects, but not
      intact osteocalcin. Whether this pathophysiological phenomenon is due to an
      accelerated bone resorption or suppressed bone formation is still obscure. In
      addition, the physiological cross-sectional area (PCSA) of muscle in the legs
      greatly decreased (from - 10% to -15%) after the flight, and it took over a month
      to be recovered in both subjects. However, the muscle volume loss in the legs
      seemed to be reversible. To examine bone and muscle metabolism with space flight,
      further investigations and international standardization of experimental
      protocols are necessary.

PMID- 9600759
TI  - Hindlimb unloading of growing rats: a model for predicting skeletal changes
      during space flight.
AB  - A model that uses hindlimb unloading of rats was developed to study the
      consequences of skeletal unloading and reloading as occurs during and following
      space flight. Studies using the model were initiated two decades ago and further
      developed at National Aeronautics and Space Administration (NASA)-Ames Research
      Center. The model mimics some aspects of exposure to microgravity by removing
      weightbearing loads from the hindquarters and producing a cephalic fluid shift.
      Unlike space flight, the forelimbs remain loaded in the model, providing a useful
      internal control to distinguish between the local and systemic effects of
      hindlimb unloading. Rats that are hindlimb unloaded by tail traction gain weight
      at the same rate as pairfed controls, and glucocorticoid levels are not different
      from controls, suggesting that systemic stress is minimal. Unloaded bones display
      reductions in cancellous osteoblast number, cancellous mineral apposition rate,
      trabecular bone volume, cortical periosteal mineralization rate, total bone mass,
      calcium content, and maturation of bone mineral relative to controls. Subsequent
      studies reveal that these changes also occur in rats exposed to space flight. In
      hindlimb unloaded rats, bone formation rates and masses of unloaded bones decline
      relative to controls, while loaded bones do not change despite a transient
      reduction in serum 1,25-dihydroxyvitamin D (1,25D) concentrations. Studies using
      the model to evaluate potential countermeasures show that 1,25D, growth hormone,
      dietary calcium, alendronate, and muscle stimulation modify, but do not
      completely correct, the suppression of bone growth caused by unloading, whereas
      continuous infusion of transforming growth factor-beta2 or insulin-like growth
      factor-1 appears to protect against some of the bone changes caused by unloading.
      These results emphasize the importance of local as opposed to systemic factors in
      the skeletal response to unloading, and reveal the pivotal role that osteoblasts
      play in the response to gravitational loading. The hindlimb unloading model
      provides a unique opportunity to evaluate in detail the physiological and
      cellular mechanisms of the skeletal response to weightbearing loads, and has
      proven to be an effective model for space flight.

PMID- 9600761
TI  - Effects of gravitational changes on the bone system in vitro and in vivo.
AB  - Spaceflight data obtained on bone cells, rodents, and humans are beginning to
      shed light on the importance of gravitational loading on the skeletal system. The
      space environment is a relevant model to explore the bone cell response to
      minimal strains. However, whether there is a direct effect of gravity on the cell
      rather than changes related to lack of convection forces in cell cultures
      performed in microgravity is unknown. In vitro studies carried out using
      osteoblastic cell cultures in space show changes in cell shape, suggesting that
      cell attachment structures as well as cytoskeleton reorganization might be
      involved. Valuable information is expected from in vitro models of an increase or
      decrease in mechanical stress in order to identify the different pathways of
      mechanoreception and mechanotransduction in the osteoblastic lineage. Results
      obtained from both humans and rodents after spaceflights indicated that bone mass
      changes are site specific rather than evenly distributed throughout the skeleton,
      thus emphasizing the need to perform measurements at different bone sites: weight
      and non-weight-bearing bones, and cancellous and cortical envelopes. Bone mass
      measurements and biochemical parameters of bone remodeling are currently under
      evaluation in cosmonauts. Histomorphometric studies of bones from rats after
      space missions of various periods provided the time course of the cancellous bone
      cellular events: transient increase in resorption and sustained decrease in bone
      formation. The underlying bone loss occurred first in weight-bearing bones and
      later in less weight-bearing bones. During the postflight period, time required
      to recover the lost bone was greater than the mission length. Thus, the
      postflight period deserves more attention than it is currently receiving. On
      earth, the rat tail-suspension model is currently used to mimic spaceflight
      induced bone loss. Data from the model confirmed the impairment of osteoblastic
      activity and showed an alteration in osteoblast recruitment with skeletal
      unloading. However, this model needs to be further validated.

PMID- 9600760
TI  - Effect of mechanical unloading and reloading on periosteal bone formation and
      gene expression in tail-suspended rapidly growing rats.
AB  - In order to delineate the influence of mechanical unloading on the formation and
      resorption of trabecular and cortical bone, the effects of mechanical unloading
      on the volume, structure, and turnover of hindlimbs were examined using tail
      suspended rapidly growing rats. In addition, to clarify the mechanism of how
      mechanical stimulation affects bone formation, the influence of reloading on the
      messenger ribonucleic acid (mRNA) expression of genes related to differentiation
      or proliferation of bone cells was examined. Tail suspension of 5-week-old rats
      for 14 days caused a suppression of the increase in the diameter, subperiosteal
      area, and bone mineral density (BMD) of the femur. The suppression of the
      increase in femoral BMD was composed of an early impairment in the gain of BMD at
      the femoral metaphysis, which is rich in trabecular bone, and a sustained
      reduction in the gain of BMD at the femoral diaphysis, which is rich in cortical
      bone. The early reduction in the increase of BMD at the metaphysis was due to an
      enhancement of bone resorption, whereas a sustained reduction of periosteal bone
      formation appeared to play an important role in the suppression of gain in
      cortical bone mass and size by mechanical unloading. Mechanical reloading of the
      hind limbs after 14 days of tail suspension caused a transient increase within 2
      h of the expression of cyclooxygenase (COX)-2 in intraosseous cells, composed
      mainly of osteocytes, and in the expression of c-fos in periosteal cells.
      However, because the COX-2 expression in osteocytes was not enhanced after 20 min
      of reloading when the c-fos expression was already increased in periosteal cells,
      the enhancement of c-fos expression does not appear to be mediated by an
      increased production of prostaglandins in the osteocytes. It is suggested that
      mechanical unloading causes an impairment of periosteal bone formation by
      impairing the expression of c-fos in periosteal cells. The intercellular
      signaling cascade that mediates the enhancement of c-fos expression in periosteal
      cells in response to mechanical stimulation remains to be elucidated.

PMID- 9600762
TI  - Summary of research issues in the animal model.

PMID- 9600763
TI  - Use of calcium tracers and biomarkers to determine calcium kinetics and bone
      turnover.
AB  - The purpose of this article is to review approaches to measuring calcium
      metabolism and bone turnover, which can be used to assess bone loss during
      spaceflight and to evaluate the effectiveness of interventions aimed at reducing
      bone loss. Isotopic tracers of calcium can be used to determine absorption,
      excretion, retention, body pool sizes, and turnover rates. Because 99% of the
      body's calcium is in the bone, calcium tracer kinetics can provide an accurate
      assessment of bone turnover rates. Biomarkers can be used to assess qualitative
      changes in bone formation and bone resorption, but they do not predict bone
      density or quantitate net calcium retention. The usefulness of biomarkers has
      been validated against calcium tracer kinetics and bone histomorphometry. Calcium
      kinetics and biomarkers of bone turnover can assess changes in calcium metabolism
      and bone turnover long before changes in bone density can be detected.

PMID- 9600764
TI  - Perspective on the impact of weightlessness on calcium and bone metabolism.
AB  - As humans venture into space to colonize the moon and travel to distant planets
      in the 21st century, they will be confronted with a bone disease that could
      potentially limit their space exploration activities or put them at risk for
      fracture when they return to earth. It is now recognized that an unloading of the
      skeleton, either due to strict bed rest or in zero gravity, leads on average to a
      1%-2% reduction in bone mineral density at selected skeletal sites each month.
      The mechanism by which unloading of the skeleton results in rapid mobilization of
      calcium stores from the skeleton is not fully understood, but it is thought to be
      related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone
      modeling and mineralization in chick embryos is not affected by microgravity,
      suggesting that bone cells adapt and ultimately become addicted to gravity in
      order to maintain a structurally sound skeleton. Strategies need to be developed
      to decrease microgravity-induced bone resorption by either mimicking gravity's
      effect on bone metabolism, or enhancing physically or pharmacologically bone
      formation in order to preserve astronauts' bone health.

PMID- 9600765
TI  - Future human bone research in space.
AB  - Skylab crewmembers demonstrated negative calcium (Ca) balance reaching about -300
      mg/day by flight day 84. Limited bone density (BMD) measurements documented that
      bone was not lost equally from all parts of the skeleton. Subsequent BMD studies
      during long duration Russian flights documented the regional extent of bone loss.
      These studies demonstrated mean losses in the spine, femur neck, trochanter, and
      pelvis of about 1%-1.6% with large differences between individuals as well as
      between bone sites in a given individual. Limited available data indicate
      postflight bone recovery occurred in some individuals, but may require several
      years for complete restoration. Long duration bedrest studies showed a similar
      pattern of bone loss and calcium balance (-180 mg/day) as spaceflight. During
      long duration bedrest, resorption markers were elevated, formation markers were
      unchanged, 1,25 vitamin D (VitD) and calcium absorption were decreased, and serum
      ionized Ca was increased. Although this information is a good beginning,
      additional spaceflight research is needed to assess architectural and subregional
      bone changes, elucidate mechanisms, and develop efficient as well as effective
      countermeasures. Space research poses a number of unique problems not encountered
      in ground-based laboratory research. Therefore, researchers contemplating human
      spaceflight research need to consider a number of unique problems related to
      spaceflight in their experimental design.

PMID- 9600766
TI  - Summary of research issues in human studies.

PMID- 9600767
TI  - On mechanosensation in bone under microgravity.
AB  - Recent research has illuminated the biological response of bone to mechanical
      loading at the cellular level, but the precise mechanosensory system that signals
      bone cells to deposit or resorb tissue has not been identified. The purpose of
      this paper is to describe the current status of this research and to suggest some
      possible mechanosensory systems by which bone cells might sense environmental
      loads. The question of whether the mechanosensory system in bone tissue is at the
      level of the cell or whether it is at the tissue level and involving the cells is
      considered here. More precisely, the following question is addressed: can an
      osteocyte or an osteoblast read the gravitational field changes directly (and
      independent of changes in its environment), or does it detect those changes
      indirectly from its environment by contact stresses as it must detect other
      changes in mechanical loading on the surface of the earth? Our strategies for
      coping with the decay of the musculoskeletal system in long term space flight are
      somewhat dependent upon the answer to this question.

PMID- 9600768
TI  - Microgravity and bone cell mechanosensitivity.
AB  - Bone cells, in particular osteocytes, are extremely sensitive to mechanical
      stress, a quality that is probably linked to the process of mechanical adaptation
      (Wolff's law). The in vivo operating cell stress derived from bone loading is
      likely a flow of an interstitial fluid along the surface of the osteocytes and
      lining cells. The response of bone cells in culture to fluid flow includes
      prostaglandin synthesis and expression of inducible prostaglandin G/H synthase
      (PGHS-2 or inducible cyclooxygenase, COX-2), an enzyme that mediates the
      induction of bone formation by mechanical loading in vivo. Disruption of the
      actin-cytoskeleton abolishes the response to stress, suggesting that the
      cytoskeleton is involved in cellular mechanotransduction. Microgravity has
      catabolic effects on the skeleton of astronauts, as well as on mineral metabolism
      in bone organ cultures. This might be explained simply as resulting from an
      exceptional form of disuse under weightlessness conditions. However, under
      microgravity conditions, the assembly of cytoskeletal elements may be altered, as
      gravity has been shown to determine the pattern of microtubular orientation
      assembled in vitro. Therefore, it is possible that the mechanosensitivity of bone
      cells is altered under microgravity conditions, and that this abnormal
      mechanosensation contributes to the disturbed bone metabolism observed in
      astronauts. In vitro experiments on the International Space Station should test
      this hypothesis experimentally.

PMID- 9600769
TI  - A nude mouse model for human bone formation in unloaded conditions.
AB  - We describe an experimental model for human bone formation in unloaded
      conditions. Bone formation has been assessed by implanting in vivo human bone
      marrow stromal cells (BMSC) on porous hydroxyapatite (HA) bioceramics
      subcutaneously in nude mice. In this system, human bone formation and remodeling
      occurs and can be studied in unloaded conditions, i.e., with no influence of
      muscle tension. Using this model system, we have been also studying the effects
      of dexamethasone (Dex) in combination with fibroblast growth factor-2 (FGF-2) on
      the osteogenic potential of human BMSC. A colony-forming unit-fibroblastoid (CFU
      F) formed in clonal conditions were significantly larger when Dex/FGF-2 was
      present in the culture medium. The cell proliferation rate was also increased by
      the combination Dex/FGF-2 at a higher extent than Dex or FGF-2 alone. BMSC
      expanded with Dex/FGF-2 displayed alkaline phosphatase levels lower (56%) than
      Dex expanded cells, but significantly higher than FGF-2 expanded cells. Our
      results suggest that Dex/FGF-2 expanded BMSC are able to form more bone than BMSC
      expanded in the presence of FGF-2 alone.

PMID- 9600770
TI  - Summary of research issues in biomechanics and mechanical sensing.

PMID- 9600771
TI  - Gene expression related to the differentiation of osteoblastic cells is altered
      by microgravity.
AB  - Bone loss is observed after exposure to weightlessness in both astronauts and
      inflight animals. Histological and biochemical studies on rats have shown a
      decrease in bone formation, probably as a result of altered osteoblast function.
      To investigate whether microgravity alters osteoblast differentiation in vitro,
      the human osteosarcoma cell line MG-63 was used as a model. MG-63 cells can be
      induced to differentiate by treating the cells with 1,25(OH)2D3 (10(-7) mol/L)
      and transforming growth factor-beta 2 (TGFbeta2) (10 ng/mL). The message level of
      differentiation-related genes was quantitated via competitive reverse
      transcription-polymerase chain reaction (RT-PCR), both in untreated and hormone
      treated cells cultured under microgravity for 9 days aboard the unmanned Foton 10
      spaceflight, and compared to ground and inflight unit-gravity cultures. At
      microgravity, gene expression for collagen Ialpha1 following treatment was
      reduced to 51% of unit-gravity levels (p < 0.05). The amount of alkaline
      phosphatase messenger ribonucleic acid (mRNA) following treatment at microgravity
      increased by only a factor of 5 compared to the tenfold increase at unit gravity
      (p < 0.02). The osteocalcin message level in treated cells cultured at
      microgravity was only 19% of the level found in cells grown at unit gravity (p <
      0.02). In conclusion, microgravity reduces the differentiation of osteoblastic MG
      63 cells in response to systemic hormones and growth factors.

PMID- 9600772
TI  - Potential role of rhIGF-I/IGFBP-3 in maintaining skeletal mass in space.
AB  - Bone loss during space flight may be induced by decreased activity of bone
      formation. To explore a new method for the bone loss in microgravity, the effects
      of insulin-like growth factor I (IGF-I), a potent stimulator for osteoblast
      activities, were studied in in vitro and in vivo system. The complex of IGF-I and
      its specific binding protein, IGFBP-3, may stimulate the osteoblastic activities
      via prolonged serum half life and increased cellular association of IGF-I. In an
      ovariectomy combined with neurectomy model, this complex stimulated bone
      turnover. IGF-I/IGFBP-3 may be a candidate for the treatment of bone loss induced
      by the microgravity.

PMID- 9600773
TI  - Noninvasive assessment of bone density and structure using computed tomography
      and magnetic resonance.
AB  - For several reasons, including low cost and radiation dose, simplicity, and the
      ability to image several skeletal sites, dual X-ray absoptiometry (DXA) is the
      most widely employed technique for diagnostic and serial assessment of integral
      bone mass in osteoporosis and other metabolic bone diseases. However, three
      dimensional imaging modalities such as quantitative computed tomography (QCT) and
      magnetic resonance (MR) imaging offer the ability to separately examine different
      factors that may play independent and important roles in osteoporosis. These
      factors include the density of the trabecular and cortical compartments as well
      as the pattern of trabecular microarchitecture. New developments in QCT include
      volumetric approaches for precise compartmental assessment of the spine and
      proximal femur as well as thin-slice tomography of the vertebral body for
      assessment of trabecular texture. In addition, ultrahigh resolution CT scanners
      (spatial resolution e50-150(i)i) have been developed for imaging of trabecular
      structure in specimens and in some cases for the peripheral skeleton (distal
      radius and phalanges). High resolution MR measurements may be employed for
      assessment of the trabecular texture at a range of peripheral sites, including
      the calcaneus, distal radius, and phalanges.

PMID- 9600774
TI  - Calcaneus as a site for the assessment of bone mass.
AB  - The calcaneus is a skeletal site frequently used for monitoring bone loss after
      spaceflight, because it is sensitive to microgravity-induced bone mineral loss
      and reflects the degree of demineralization in the vertebra and the femoral neck.
      In this article, methods for assessing the calcaneus are reviewed, and their
      potential applications and limitations as the monitoring site for bone loss in
      weightlessness are discussed. Currently, single or dual energy X-ray
      absorptiometry appears to be most sensitive for monitoring bone mineral loss in
      weightlessness. The results of recent studies suggest two- to threefold longer
      follow-up times required for ultrasound techniques. However, ultrasound devices
      can be designed to be portable, making them attractive for inflight use, and
      ultrasound techniques are expected to provide information related to bone
      quality. Additional investigations that assess new ultrasound techniques would be
      important to determine and utilize the full potential of this technology for
      monitoring bone loss in weightlessness.

PMID- 9600775
TI  - Summary of research issues in imaging and noninvasive bone measurement.

PMID- 9600776
TI  - Impact of spatial resolution on the prediction of trabecular architecture
      parameters.
AB  - Although the efficacy of various measures for the assessment of trabecular bone
      architecture has been widely studied, the impact of spatial resolution on the
      estimation of these measures has remained relatively unexplored. In this study,
      ten cubes each of human trabecular bone from the femur and vertebral bodies were
      obtained from nine cadavers (four males and five females), aged 23-67 years (mean
      42.3 years). These specimens were serially milled and imaged at a resolution of
      40 microm to produce three-dimensional digitizations from which traditional
      morphometric and structural anisotropy measures could be computed based on a
      three-dimensional approach. The cubes were then artificially degraded to an in
      plane resolution of 100 microm and an out-of-plane (slice) resolution of 100-1000
      microm. These resolutions mimicked in vivo resolutions as seen using magnetic
      resonance (MR) imaging. All images, original and degraded, were individually
      segmented using a thresholding algorithm, and both the traditional morphometric
      and structural anisotropy measures were recomputed. The choice of slice direction
      was varied along the superior-inferior (axial), anterior-posterior (coronal), and
      medial-lateral (sagittal) directions to minimize the impact of the lower slice
      resolution on the architectural measures. It was found that traditional
      morphometric measures such as trabecular spacing and trabecular number showed
      weak resolution dependency; measures such as trabecular thickness, however,
      showed strong resolution dependency and required very high resolutions for
      precise measurement. In the case of the femur specimens, both structural
      anisotropy as well as the preferred orientation showed a strong resolution
      dependency. The resolution dependency of these parameters could be minimized for
      the femur and the vertebral body specimens if the slice direction was taken along
      the superior-inferior direction.

PMID- 9600777
TI  - High-resolution magnetic resonance imaging: three-dimensional trabecular bone
      architecture and biomechanical properties.
AB  - The purpose of this study was to use high-resolution magnetic resonance (MR)
      imaging combined with image analysis to investigate the three-dimensional (3D)
      trabecular structure, anisotropy, and connectivity of human vertebral, femoral,
      and calcaneal specimens. The goal was to determine whether: (a) MR-derived
      measures depict known skeletal-site-specific differences in architecture and
      orientation of trabeculae; (b) 3D architectural parameters combined with bone
      mineral density (BMD) improve the prediction of the elastic modulus using a
      fabric tensor formulation; (c) MR-derived 3D architectural parameters combined
      with BMD improve the prediction of strength using a multiple regression model,
      and whether these results corresponded to the results obtained using higher
      resolution depictions of trabecular architecture. A total of 94 specimens (12 x
      12 x 12 mm cubes) consisting of trabecular bone only were obtained, of which
      there were 7 from the calcaneus, 15 from distal femur, 47 from the proximal
      femur, and 25 from the vertebral bodies. MR images were obtained using a 1.5
      Tesla MR scanner at a spatial resolution of 117 x 117 x 300 microm. Additionally,
      BMD was determined using quantitative computed tomography (QCT), and the
      specimens were nondestructively tested and the elastic modulus (YM) was measured
      along three orthogonal axes corresponding to the anatomic superior-inferior
      (axial), medial-lateral (sagittal), and anterior-posterior (coronal) directions.
      A subset of the specimens (n=67) was then destructively tested in the superior
      inferior (axial) direction to measure the ultimate compressive strength. The MR
      images were segmented into bone and marrow phases and then analyzed in 3D.
      Ellipsoids were fitted to the mean intercept lengths, using single value
      decomposition and the primary orientation of the trabeculae and used to calculate
      the anisotropy of trabecular architecture. Stereological measures were derived
      using a previously developed model and measures such as mean trabecular width,
      spacing, and number were derived. Because the spatial resolution of MR images is
      comparable to trabecular bone dimensions, these measures may be subject to
      partial volume effects and were thus treated as apparent measures, such as BV/TV,
      Tb.Sp, Tb.N, and Tb.Th rather than absolute measures, as would be derived from
      histomorphometry. In addition, in a subset of specimens, the Euler number per
      unit volume was determined to characterize the connectivity of the trabecular
      network. There were significant differences in the BMD, trabecular architectural
      measures, elastic modulus, and strength at the different skeletal sites. The
      primary orientation axes for most of the specimens was the anatomic superior
      inferior (axial) direction. Using the fabric tensor formulation, in addition to
      BMD, improved the prediction of YM (SI), while including some of the
      architectural parameters significantly improved the prediction of strength. In
      comparing MR-derived 3D measures with those obtained from 20 microm optical
      images (n=18; 9 vertebrae, 9 femur specimens), good correlations were found for
      the apparent Tb.Sp and Tb.N, moderate correlation was seen for the apparent
      BV/TV, and poor correlation was found for the apparent Tb.Th. Using these higher
      resolution images, the fabric tensor formulation for predicting the elastic
      modulus also showed improved correlation between the measured and calculated
      modulus in the axial (SI) direction. In summary, high-resolution MR images may be
      used to assess 3D architecture of trabecular bone, and the inclusion of some of
      the 3D architectural measures provides an improved assessment of biomechanical
      properties. Further studies are clearly warranted to establish the role of
      architecture in predicting overall bone quality, and the role of trabecular
      architecture measures in clinical practice. (ABSTRACT TRUNCATED)

PMID- 9600778
TI  - Bisphosphonates stimulate formation of osteoblast precursors and mineralized
      nodules in murine and human bone marrow cultures in vitro and promote early
      osteoblastogenesis in young and aged mice in vivo.
AB  - Recent in vitro findings suggest that bisphosphonates, potent inhibitors of
      osteoclastic bone resorption, may also have a direct action on osteoblasts. The
      purpose of this study was to search for potential effects of etidronate and
      alendronate on the formation of early and late osteoblastic cell precursors by
      measuring the number of colony-forming units for fibroblasts (CFU-F) and colony
      forming units for osteoblasts (CFU-OB) in murine and human bone marrow cultures.
      In murine marrow cultures, etidronate (10(-5) to 10(-9) mol/L) significantly
      stimulated the formation of CFU-F with a maximal effect at 10(-5) mol/L (mean
      increase over control values+/-SD: 106+/-17%;p < 0.001), whereas alendronate had
      a biphasic effect, being stimulatory at concentrations below 10(-7) mol/L (78+/
      5%; p < 0.001), and inhibitory at higher doses. The formation of CFU-OB was also
      inhibited by both bisphosphonates at the highest concentrations (10(-5) mol/L and
      10(-6) mol/L), but it was significantly stimulated at lower concentrations (from
      10(-7) to 10(-9) mol/L for etidronate and 10(-7) to 10(-10) mol/I, for
      alendronate; p < 0.001). In human bone marrow cultures, alendronate (10(-8) to 10
      (12) mol/L) increased CFU-F formation with a maximal effect at 10(-10) mol/L
      (161+/-12 %; p < 0.01). CFU-OB formation, observed only in the presence of
      dexamethasone (10(-8) mol/L), was markedly stimulated by alendronate at the above
      concentrations with a maximal increase at 10(-10) mol/L (133+/-34%; p < 0.001).
      The in vivo short-term effects of bisphosphonates on the formation of early
      osteoblast precursors were also studied in bone marrow cultures from young female
      mice treated with weekly subcutaneous injections of etidronate (0.3, 3, and 30
      mg/kg) or alendronate (0.3, 3, and 30 microg/kg) and from aging female mice
      treated with the two lowest doses of both drugs. After 1 month of treatment,
      etidronate (0.3 and 3 mg/kg) and alendronate (0.3 and 3 microg/kg) significantly
      increased the number of CFU-F colonies in the bone marrow from young and old
      animals, whereas the highest dose of both drugs had no effect in young mice. Our
      results, together with previously reported observations of bone-forming effects
      in osteoporosis, suggest that bisphosphonates may have, in vivo, a potentially
      relevant influence on cells of the osteoblastic lineage, distinct from their
      inhibitory action on osteoclasts.

PMID- 9600779
TI  - Recruitment and proliferative responses of osteoblasts after mechanical loading
      in vivo determined using sustained-release bromodeoxyuridine.
AB  - Mechanical bending of a rat's tibia in vivo can increase endocortical bone
      formation by over sixfold. It has been proposed that mechanical loading increases
      bone formation by driving osteoprogenitor cells in the marrow stroma to progress
      through the cell cycle and subsequently differentiate into osteoblasts at the
      cortical bone surfaces. We used a sustained-release preparation of 5-bromo-2'
      deoxyuridine (SR-BrdUrd) to determine the origin of endocortical osteoblasts in
      rat tibiae after mechanical loading. SR-BrdUrd was bioavailable for the entire 96
      h duration of the experiments, so all cells that progressed through a cell cycle
      were labeled with BrdUrd. Although the endocortical osteoblast surface was
      significantly increased (p < 0.05) at 48 h after loading, the percentage of
      BrdUrd-labeled osteoblasts did not increase, suggesting that the newly
      differentiated osteoblasts on the endocortical surface did not originate from
      proliferating cells. At 96 h after loading, 30-40% of the endocortical
      osteoblasts were BrdUrd labeled. The majority of BrdUrd-labeled osteoblasts
      appeared on the endocortical bone surface within the third day after loading,
      indicating that proliferation and differentiation of precursors into endocortical
      osteoblasts required 72 h after the loading stimulus. These results indicate that
      mechanical loading can cause two distinct osteoblastic responses: an immediate
      response within 48 h in which osteoblasts are recruited from nondividing
      preosteoblasts and/or bone-lining cells, and a delayed response involving
      proliferation and differentiation of preosteoblasts that requires > or =3 days.

PMID- 9600780
TI  - Formoterol and isoproterenol induce c-fos gene expression in osteoblast-like
      cells by activating beta2-adrenergic receptors.
AB  - Formoterol, a beta2-adrenergic agonist has been shown in ovariectomized rat
      models to have anabolic effects on bone. However, those studies did not determine
      whether the effect of formoterol was by a direct action on bone cells themselves
      or indirectly via anabolic action on muscle. To address the question of whether
      formoterol could directly affect osteoblast function we investigated the
      expression patterns of beta3-adrenergic receptors (betaARs) in human osteoblast
      like cells and functional coupling to gene expression. Northern blot analysis
      showed that betaAR subtypes are expressed at different levels in the osteoblast
      like cell lines TE-85, SaOS-2, MG-63, and OHS-4. beta1AR expression was found in
      SaOS-2, OHS-4, and TE-85, but not MG-63 cells. beta2ARs are expressed at higher
      levels in MG-63 cells than in TE-85 and SaOS-2 cells, but were not detected in
      OHS-4 cells. PCR analysis paralleled the northern blot analysis except that
      beta3AR expression was found in one of three human primary osteoblast cDNAs
      tested. beta3AR expression was not found in any of the osteoblast-like cell
      lines. The nonspecific betaAR agonist, isoproterenol, and the beta2AR-specific
      agonist, formoterol, induced c-fos gene expression in cultured SaOS-2 cells in an
      immediate early fashion. This effect was inhibited by the beta2AR-specific
      antagonist, ICI 118551, but not by the beta1AR-specific antagonist, CGP 20712,
      indicating that induction of c-fos gene expression is specifically mediated by
      beta2ARs. c-fos gene expression was induced by both isoproterenol and formoterol
      via increases in cAMP, which in turn activated the cAMP/PKA pathway; the PKA
      inhibitor, H89, inhibited c-fos gene expression. Thus, betaARs are expressed in
      osteoblast-like cells and are coupled to c-fos gene expression via the beta2AR,
      increases in cAMP levels and activation of a PKA-dependent pathway.

PMID- 9600781
TI  - Changes in osteoblast phenotype during differentiation of enzymatically isolated
      rat calvaria cells.
AB  - Osteoblasts enzymatically isolated from newborn rat calvariae show various
      phenotypes including formation of mineralized bone nodules in culture. We
      investigated the temporal changes in osteoblast phenotype in these cells up to
      day 20 in culture. These cells formed unmineralized nodules by day 5.
      Mineralization was observed at the center of nodules by day 10, and nodules
      became larger on day 15. The nodules were surrounded by numerous alkaline
      phosphatase (ALP)-positive cells. ALP activity gradually increased by day 20.
      Parathyroid hormone (PTH) responsiveness increased with time in culture.
      Osteoblasts produced no osteocalcin by day 10, but its synthesis was detected
      from day 15. These cells expressed substantial levels of ALP and PTH/PTHrP
      receptor mRNAs as early as day 5 in culture, but very weak expression of
      osteocalcin mRNA on day 5. The levels of expression of these transcripts
      increased with time in culture. In situ hybridization demonstrated that PTH/PTHrP
      receptor and osteocalcin mRNAs were strongly expressed in nodules, but the former
      appeared much earlier than the latter. BMP-2 and BMP-4 mRNAs also appeared in the
      cells forming nodules. Immunohistochemical analysis demonstrated that cells
      expressing either BMP-2/4 or their receptors (BMPR-IA, BMPR-IB, and BMPR-II)
      preferentially appeared in nodules. These observations suggested that BMPs play
      an important role in the formation of mineralized bone nodules in an autocrine
      and/or paracrine fashion in these cells. The present study confirmed that
      osteoblasts enzymatically isolated from newborn rat calvariae are a useful tool
      for studying the differentiation process of osteoblasts.

PMID- 9600782
TI  - Expression of IL-6 receptor and GP130 in mouse bone marrow cells during
      osteoclast differentiation.
AB  - Interleukin-6 (IL-6) has been postulated as a possible mediator of bone loss
      after estrogen deficiency, and its signal is transduced via glycoprotein 130
      (gp130) after binding IL-6 receptor (IL-6R) in the membrane of target cells. In
      this study, the expression of IL-6R and gp130 in bone marrow cells during
      osteoclast differentiation was investigated. Mouse bone marrow cells were
      isolated and cultured with or without 1alpha,25-dihydroxyvitamin D3
      [1,25(OH)2D3]. During the formation of tartrate-resistant acid phosphatase (TRAP)
      positive multinucleated cells (MNCs), IL-6R and gp130 expression in the
      mononuclear cells, stromal cells, and TRAP-positive MNCs were quantitated, using
      a laser cytometer with a fluorescence confocal microscopy. With 1,25(OH)2D3
      stimulus, the level of gp130 significantly increased, but that of IL-6R did not
      in the stromal cells. In contrast, the levels of both gp130 and IL-6R
      significantly increased in the mononuclear cells by the treatment with
      1,25(OH)2D3. The high expression of both gp130 and IL-6R was observed in the TRAP
      positive mononuclear cells. Moreover, both IL-6R and gp130 were expressed in the
      TRAP-positive MNCs and isolated murine osteoclasts. The treatment of TRAP
      positive MNCs with IL-6 caused enhancement of the resorbing activity in a dose
      dependent manner, and the effect was prevented by a neutralizing antibody against
      IL-6R. These data suggest that gp130 and IL-6R, as well as IL-6, are involved in
      the formation and activation of osteoclasts.

PMID- 9600783
TI  - High extracellular Ca2+ and Ca2+-sensing receptor agonists activate nonselective
      cation conductance in freshly isolated rat osteoclasts.
AB  - The effects of an increase of extracellular and intracellular Ca2+ on the
      membrane properties were examined in freshly isolated rat osteoclasts using the
      perforated patch-clamp method. Spread-type osteoclasts plated on a cover glass
      predominantly displayed an inwardly rectifying K+ current in a normal saline
      solution. Application of an extracellular high-Ca2+ solution transiently
      increased the membrane conductance in 15 (71%) of 21 osteoclasts. The external
      high Ca2+-induced current reversed at the membrane potential of -4.8+/-2.4 mV
      (n=8). The change of intracellular Cl-concentration did not affect the reversal
      potential, suggesting that the response was due to a nonselective cation
      conductance. Application of a calcium ionophore, ionomycin (3 micromol/L),
      continuously increased the membrane conductance, and the reversal potential was 
      12.5+/-5.0 mV (n=5). Extracellularly applied neomycin (100 micromol/L) and Gd3+
      (100 micromol/L), which are agonists of Ca2+-sensing receptor (CaR), also
      increased the membrane conductance. These results suggest that rat osteoclasts
      detect high extracellular Ca2+ by an extracellular Ca2+-sensing mechanism
      functionally similar to the CaR in the cell surface, release Ca2+ from the
      internal stores, and display the activation of Ca2+-dependent cation channels in
      the cell membrane.

PMID- 9600784
TI  - Effects of estrogen on the concentration of insulin-like growth factor-I in rat
      bone matrix.
AB  - Insulin-like growth factor-I (IGF-I) plays an important role in bone metabolism,
      but data on the regulation of IGF-I in bone tissue in vivo are still limited. In
      the present study, we examined the effects of ovariectomy (ovx) and estrogen
      replacement on the skeletal concentration of IGF-I in the femur shaft of 6-10
      week-old female rats. Ovx had no consistent effect on bone matrix IGF-I
      concentration regardless of animal age at ovx. In contrast, administration of
      estradiol in doses that exceeded physiological replacement (50 and 150 nmol/kg
      per day, subcutaneously) significantly increased the bone matrix IGF-I
      concentration. These are the first in vivo data which demonstrate that estrogens
      are capable of increasing the concentration of IGF-I in bone tissue. However,
      this stimulatory effect appears to be limited to supraphysiological estrogen
      concentrations.

PMID- 9600785
TI  - Bone mineral density and biomechanical properties of spine and femur of
      ovariectomized rats treated with naproxen.
AB  - Prostaglandins have been reported to mediate the effects of ovariectomy on bone
      loss. We studied the effect of naproxen, an inhibitor of production of
      prostaglandins, on ovariectomy-induced bone loss. One hundred forty female Wistar
      rats 4.5 months of age were divided into groups of baseline, sham operation
      (sham), sham treated with naproxen at 10 mg/kg per day (in food), and ovariectomy
      treated with naproxen or estrogen as intramuscular injection of estradiol at 0.2
      mg/kg body weight per week. They were killed 3, 6, and 9 months postsurgery. Bone
      mineral density (BMD) of the lumbar spine (L1-4), femoral neck, midshaft, and
      distal metaphysis was determined using dual-energy X-ray absorptiometry (DXA) in
      vitro. The compressive test of the L1 vertebral body and torsional test of the
      left femur were performed. The right femoral neck and femoral midshaft were
      processed undecalcified for determining cross-sectional moments of inertia.
      Naproxen treatment partially prevented ovariectomy-induced loss or less gain in
      BMD, in a significant manner, in the femoral neck cortical area, and also in L1
      compressive strength and stiffness. Estrogen fully prevented these ovariectomy
      induced effects. Naproxen showed no effect on ovariectomy-induced improvement in
      femoral torsional strength and stiffness and cross-sectional moments of inertia.
      No statistically significant difference was found between naproxen-treated sham
      rats and untreated sham rats. The data suggest that naproxen partially prevents
      ovariectomy-induced osteopenia.

PMID- 9600786
TI  - Bone responses at various skeletal sites to human parathyroid hormone in
      ovariectomized rats: effects of long-term administration, withdrawal, and
      readministration.
AB  - This study was undertaken to examine bone responses to human parathyroid hormone
      (hPTH) at various skeletal sites. Forty 6-month-old female Wistar rats were
      divided into four groups, and bilateral ovariectomy (ovx) was performed in three
      of the four groups (n=30). The other group (n=10) received sham surgery (sham).
      Four weeks after the ovx, hPTH(1-34) administration was started. The ovx rats
      received 5 microg/kg per day of PTH (PTH-5; n=10), 10 microg/kg per day of PTH
      (PTH-10; n=10), or vehicle (PTH-v; n=10), three times a week for 24 weeks.
      Thereafter, PTH was withdrawn for 16 weeks followed by readministration at the
      same dosage for 8 weeks. The bone mineral content (BMC) at the whole skeleton and
      the bone mineral density (BMD) at the lumbar vertebrae, caudal vertebrae, distal
      femur, diaphysis of the femur, proximal tibia, and skull were longitudinally
      measured by dual-energy x-ray absorptiometry (DXA) at 4-week intervals during the
      experimental period. Thirteen rats that died during the experimental period were
      excluded from the analysis. As a result, the whole skeleton showed an increase in
      BMC during the PTH administration, whereas no withdrawal or readministration
      effects were observed. The metaphysis showed a highly sensitive bone response,
      while the lumbar vertebrae and diaphysis showed a moderate magnitude of changes
      in bone mass during the PTH administration. The skull and the caudal vertebrae
      did not show sensitive responses to PTH. After withdrawal, the BMD was markedly
      decreased at the sites that showed marked increases in BMD after PTH
      administration. The PTH readministration increased the BMD again at the sites
      that showed sensitive responses after the initial administration. Strength tests
      were also performed when the readministration was completed. The ultimate loads
      for the femur and vertebral body in the PTH-treated groups were significantly
      higher than those in the vehicle-treated group. In conclusion, the response to
      PTH in ovx rats varied among skeletal sites; withdrawal-related decreases were
      marked at the sites showing marked increases in bone mass related to PTH
      administration, and PTH readministration may be sufficiently effective.

PMID- 9600787
TI  - Effects of a weekly injection of human parathyroid hormone (1-34) and withdrawal
      on bone mass, strength, and turnover in mature ovariectomized rats.
AB  - One hundred fifteen Wistar rats, 7 months of age, were ovariectomized (ovx) or
      sham-operated to evaluate the effects of a weekly injection of human parathyroid
      hormone (hPTH) and withdrawal on the bone mass, strength, and turnover in mature
      ovariectomized rats. At 3 months, ovx rats were given a weekly injection of
      hPTH(1-34) at the respective doses of 0 (vehicle), 10, and 90 microg/kg body
      weight (BW) for 3 months. Then, hPTH-treated rats were divided into two groups
      each: continuously treated groups, and the groups treated with vehicle only for
      another 3 months. Weekly hPTH injections at doses of 10 or 90 microg/kg BW
      maintained the lumbar BMD values and increased the values of the femoral cortical
      bone, increasing the bone formation rates in the trabecular, endocortical, and
      periosteal envelopes. Trabecular osteoclasts were increased in the 90 microg/kg
      dose group. Trabecular bone surface relative to the volume was decreased by hPTH.
      The compressive load of the lumbar bone and the bending moment of the midfemur
      were increased. The lumbar compressive load values, corrected for BMD and volume,
      and the moment of inertia of the midfemur were also increased. The intracortical
      porosity values were not increased by the treatment. After withdrawal of hPTH
      treatment, the BMD values in both the lumbar and the midfemur were reduced to ovx
      control levels. The bone mass stimulated by the 90 microg/kg dose was reduced
      faster than that by the 10 microg/kg dose. However, the parameters of bone
      strength were still larger than those of the ovx controls after cessation of the
      hPTH treatment. Thus, a weekly hPTH injection effectively stimulated the bone
      formation in both the trabecular and cortical bone, leading to positive effects
      on mass and structure of the bone. These data suggest the possibility of benefits
      of both a lower frequency of hPTH injections as well as high-frequency injections
      for human osteoporotics.

PMID- 9600788
TI  - Effects of progestins on the metabolism of cancellous bone in aged
      oophorectomized rats.
AB  - The effects of progestins on bone loss in female oophorectomized (ovx) rats were
      evaluated. One-year-old Sprague-Dawley rats were divided into eight groups: (1)
      beginning controls (control); (2) sham-operated controls (sham); (3) ovx; (4) ovx
      treated with estrogen (ovx + E); (5) ovx treated with progesterone (ovx + P); (6)
      ovx treated with estrogen and progesterone (ovx + E + P); (7) sham group treated
      with estrogen (sham + E); and (8) sham group treated with progesterone (sham +
      P). Immediately after surgery, the rats in the hormone injected groups were
      subcutaneously (s.c.) injected daily for 15 weeks with estrogen (17-beta
      estradiol, 0.01 mg/kg in ethanol), or progesterone (4-pregnene-3,20-dione, 0.1
      mg/kg in ethanol), or both. At the end of 15 weeks, the bone mineral density
      (BMD) and bone histomorphometry of the rats' lumbar vertebrae and serological
      parameters were measured. In the sham, ovx, and ovx + P groups, treatment with
      progesterone alone did not maintain the BMD in the lumbar vertebrae, but in the
      ovx + E and ovx + E + P, sham + E, and sham + P groups, progesterone did not
      inhibit the action of estrogen in the aged ovx rat model. BMD in the sham + P
      group was significantly higher than in the sham group (270.8+/-10.8 mg/cm2 versus
      253.6+/-10.2 mg/cm2; p < 0.01). Bone histomorphometry revealed that bone volume
      (BV/TV) increased more in the ovx + E + P group than in the ovx + E group and
      more in the sham + P group than in the sham group, but not significantly. The ovx
      + E, ovx + E + P, sham + E, and sham + P groups showed no significant differences
      in the bone formation and resorption parameters, but the bone formation variables
      tended to increase in the ovx + E + P and sham + P groups. We concluded that
      progesterone alone cannot prevent bone loss or the increase in turnover after ovx
      and that estrogen, not progesterone, accounted for all of the bone activity in
      this study. It seems doubtful that progesterone inhibits the action of estrogen,
      and in fact may have a beneficial effect on bone metabolism.

PMID- 9600789
TI  - Morphometric skeletal traits, femoral measurements, and bone mineral deposition
      in mice with agonistic selection for body conformation.
AB  - Morphometric skeletal traits, femoral histomorphometry, and bone mineral
      deposition were investigated in two lines of mice (CBi+ and CBi-) divergently
      selected for body conformation (CBi+: high body weight, long tail; CBi-: low body
      weight, short tail) and in the unselected control line CBi. Linear morphometric
      measurements, absolute and relative skeletal weights, absolute and relative
      femoral weights, and total biomass sustained per unit of total or tail-less
      skeletal weight were increased in CBi+ mice in comparison with controls. This
      greater biomass implies a greater mechanical demand that is satisfied by a
      heavier skeleton. Looking specifically to the femur, CBi+ mice had heavier bones,
      both absolute and relative, with a greater diameter and a greater cortical
      thickness, resulting in a greater cortex/diameter ratio than controls. Although
      morphometric measurement and absolute skeletal weight were lower in CBi- than in
      CBi mice, the relative skeleton weight and the biomass sustained per unit of
      skeletal weight were not modified in the downward selection line when compared
      with controls. Therefore, CBi- mice did not exhibit a greater mechanical demand
      as CBi+ mice did. These results led us to consider at least three main aspects:
      bone length growth; cortical thickness/bone diameter ratio; and bone
      calcification. The long bones appeared to have a genetically determined
      predisposition to achieve a given length, which, however, could be modified by
      artificial selection. Cortical thickness would be directly related to the biomass
      sustained. This variable increased in CBi+ mice, a genotype that supports a
      greater biomass than controls, and did not change in CBi- mice, which sustained
      the same biomass as CBi. The pattern of mineral deposition did not accompany the
      functional demand because it was higher in CBi- than in CBi+; however, as
      artificial selection separately affected bone material quality and bone
      architectural design, these genotypes could express architectural modifications
      that override any change in bone material quality.

PMID- 9600790
TI  - Effects of pregnancy and lactation on bone in cynomolgus macaques:
      histomorphometric analysis of iliac biopsies.
AB  - The effects of pregnancy and lactation on bone histomorphometry have been studied
      extensively in rats and dogs. However, these models differ greatly in
      reproductive physiology compared with women. The purpose of this study was to
      evaluate histomorphometric changes in iliac crest bone biopsies taken from
      cynomolgus monkeys (Macaca fascicularis), animals similar to women both
      skeletally and reproductively. After fluorochrome labeling, paired iliac crest
      bone biopsies were collected and subjected to structural and dynamic
      histomorphometric analyses during the third trimester and 3 months postpartum in
      one group (n=16), at 3 and 9 months postpartum in the second group (n=14), and at
      4 month intervals in a nonpregnant control group (n=6). Serum was collected at
      the time of surgery to measure total alkaline phosphatase (ALP), bone gla-protein
      (BGP), calcium, and estradiol. Trabecular thickness increased significantly
      between 3 and 9 months postpartum. Bone formation rates did not differ between
      control and pregnant monkeys, but were significantly increased during lactation
      (3 months postpartum) and remained elevated at 9 months postpartum. ALP and BGP
      levels were elevated at 3 months postpartum, compared with levels during
      pregnancy, and remained elevated at 9 months postpartum. Estradiol concentrations
      were greatly elevated during pregnancy, dropped below normal nonpregnant levels
      by 3 months postpartum, and remained suppressed at 9 months postpartum. These
      results suggest that, during the third trimester, the rate of bone turnover was
      not altered, but lactational demands for calcium were met in part by increased
      bone turnover.

PMID- 9600791
TI  - Dual-energy X-ray absorptiometry in predicting mechanical characteristics of rat
      femur.
AB  - Dual-energy X-ray absorptiometry (DXA), geometrical measurements, and mechanical
      testing of the rat femoral shaft and neck were performed on both femora of 51
      Sprague-Dawley rats to: (i) determine the reproducibility of the DXA,
      geometrical, and biomechanical measurements of rat femora; (ii) determine linear
      and power-law (y=ax(b)) associations between the site-specific bone mineral
      variables and the actual mechanical characteristics of the given sites; (iii)
      develop, if sufficiently strong associations were found, appropriate prediction
      equations for the breaking load (F) and flexural rigidity (EI) of the femoral
      shaft and neck (only for F); and (iv) validate these equations in terms of
      accuracy of prediction. In the majority of the DXA measurements, the
      repeatability of the measurements was good, the CVrms varying between 1.2% and
      3.9% in the bone mineral density (BMD) measurements and between 1.6% and 13.8% in
      the bone mineral content (BMC) measurements. DXA also proved accurate in length
      measurements of the rat femur (measurement error <1%). The manual (digimatic
      caliper-obtained) geometrical measurements of the rat femora were equally
      precise, the CVrms values varying between 0.2% and 5.0%. The repeatability of the
      biomechanical testings of these femora varied between 5.0% and 14.7%. Virtually
      all of the power-law and linear models explained more than 80% (at best 97%) of
      the variation in the F of the femoral shaft and neck, and the EI of the femoral
      shaft. Despite the high group-level correlations between the DXA-based
      predictions of bone strength and the actual breaking loads of the rat femora, and
      good precision of DXA, the ability of any DXA-based estimate to predict
      accurately the actual biomechanical characteristics of an individual bone
      remained relatively poor. In extreme cases, the prediction error could be tens of
      percent. Despite this we feel that bone strength-estimating equations can be used
      in the group-level analyses of experimental and clinical studies. Care must be
      taken, however, when choosing the most appropriate prediction method for a
      particular study.

PMID- 9600792
TI  - Changes in biochemical markers and bone mass after withdrawal of ibandronate
      treatment: prediction of bone mass changes during treatment.
AB  - The study was a 1 year randomized, double-blind, placebo-controlled study of
      ibandronate treatment in postmenopausal, osteopenic women. Participants were
      followed for 1 year after withdrawal of treatment. All women were at least 10
      years past menopause and had a baseline bone mineral density (BMD) at the distal
      forearm at least 1.5 standard deviations below the premenopausal mean peak value.
      A total of 141 women (78%) completed the first year, and 119 women (66%) the
      second year of the study. The dose-response data of the first year have been
      published previously (Ravn et al. Bone 19:527-533;1996). In this study, we
      analyzed the biochemical markers as predictors of response in bone mass during
      ibandronate treatment, and report withdrawal data from the last year of the
      study, when ibandronate was discontinued. The relative change in the biochemical
      markers was significantly correlated to the response in BMD. At 12 months, the r
      values ranged from -0.29 to -0.47 (p < 0.01) and were highest for CrossLaps (uCL)
      and osteocalcin (OC(N-MID)). The quartiles of women with the most reduced
      concentrations of uCL and OC(N-MID) during treatment showed a 360-430% higher
      response in BMD compared to quartiles with less reduced concentrations (p <
      0.01). During the withdrawal period, uCL and alkaline phosphatase (AP) returned
      to baseline values 12 months after discontinuation of treatment in all groups,
      whereas OC(N-MID) and bone-specific AP were still reduced 10%-25% in the groups
      previously treated with the highest doses of ibandronate (1.0-5.0 mg) (p < 0.01).
      In the withdrawal period, BMD decreased equally in all groups (analysis of
      variance; not significant); with a linear rate of 2%/year on average (p < 0.05 to
      < 0.001) at the spine and femur. In conclusion, uCL and OC(N-MID) can be used to
      predict the response in bone mass during ibandronate treatment. The bone loss
      that resumes after withdrawal of ibandronate treatment is of a magnitude similar
      to that of normal postmenopausal bone loss.

PMID- 9600793
TI  - Bone measurements in asymptomatic primary hyperparathyroidism.
AB  - A large proportion of patients with asymptomatic primary hyperparathyroidism
      (PHPT) have some degree of bone involvement which appears to be relatively
      greater for cortical than trabecular bone. However, the clinical meaning and
      pathophysiologic basis of this observation are unknown. In 77 postmenopausal
      women with asymptomatic PHPT, bone mineral density (BMD) was measured at the
      proximal and ultradistal forearm, the lumbar spine, the femoral neck, and Ward's
      triangle by dual-energy X-ray absorptiometry. The digitalized X-ray pictures of
      the nondominant hand were obtained from all patients and from 680 healthy
      postmenopausal women, to measure the outer (D) and inner (d) diameter of the
      second metacarpus. The cortical area per total area (CA/TA) and a bending
      breaking resistance index (D4-d4/D) were then calculated. In 29 of the patients
      not operated on and in 30 healthy pair-matched women, a second X-ray of the hand
      was obtained 5-12 years afterward. In patients with PHPT, the z score of CA/TA
      was significantly lower than zero [-0.97+/-0.99, standard deviation (SD)]. This
      is due to an enlargement of the inner diameter, despite a significant increase in
      the z score for the outer diameter. The z score of the DXA measurements was
      significantly lower than zero for the lumbar spine (-0.59+/-1.26), ultradistal
      radius (-1.03+/-0.91), proximal radius (-1.91+/-1.80), and Ward triangle (-1.81+/
      1.07), but not for the femoral neck (-0.36+/-1.03). In subjects in whom two X
      rays were obtained, per-decade endosteal resorption and periosteal apposition
      were statistically significant only in the PHPT patients. Both endosteal
      resorption and periosteal apposition were significantly greater in PHPT patients
      compared to healthy controls. The mean BBRI in PHPT patients was not different
      from that in controls, but the longitudinal changes were significantly greater
      than those observed in control subjects. Our radiogrammetry data may provide an
      original clue for understanding preferential cortical bone loss in PHPT patients.
      In cross-sectional and longitudinal studies, we have shown that in PHPT, both
      endosteal bone resorption and periosteal apposition are augmented. The former
      effect is predominant, which leads to significant diminution of cortical
      thickness. As a consequence of the enlargement of long bones, the areal BMD is
      somewhat underestimated, since the same amount of cortical bone is divided by a
      greater diameter. Furthermore, in term of mechanical properties, the increases in
      the cross-sectional area of appendicular bone segments might compensate in part
      for both the diminution of cortical thickness and a greater porosity of cortical
      bone.

PMID- 9600794
TI  - Vitamin D receptor alleles do not predict bone mineral density or bone loss in
      Danish perimenopausal women.
AB  - A BsmI restriction enzyme polymorphism in the vitamin D receptor (VDR) gene has
      been reported to be associated with bone mineral density (BMD) and bone turnover.
      However, findings in other studies suggest the presence of considerable
      interaction by race, body size, and environmental factors. Therefore, we VDR BsmI
      genotyped 200 healthy perimenopausal Danish white women (mean age 50.8 years,
      mean calcium intake 900 mg/day) in a comprehensive, longitudinal, community-based
      population study. Bone loss was assessed by dual-energy X-ray absorptiometry
      (DXA) using cross-calibrated Hologic QDR-1000W and QDR-2000 densitometers, with a
      mean follow-up period of 4 years (range 1-5 years). Despite a distribution of
      genotypes similar to that of other white populations (28% bb, 49% Bb, 23% BB),
      VDR genotypes were not associated with lumbar or femoral baseline BMD, subsequent
      bone loss rates, or biochemical markers of bone metabolism (bone-specific
      alkaline phosphatase, urinary hydroxyproline, and serum osteocalcin). Controlling
      for body size, calcium intake, and serum levels of 25-hydroxyvitamin D3
      [25(OH)D3] did not alter this finding. The possible existence of a threshold
      effect was subsequently investigated by restricting analysis to women with low
      serum 25(OH)D3 levels or low calcium intake. VDR BsmI genotypes showed no
      significant impact on bone density or bone loss in healthy Danish early
      postmenopausal women, even when allowance was made for calcium intake, serum
      25(OH)D3, and body size.

PMID- 9600795
TI  - Clodronate is effective in preventing corticosteroid-induced bone loss among
      asthmatic patients.
AB  - Clodronate is a novel drug used for inhibiting osteoclastic activity. The aim of
      the present double-blind study was to evaluate the efficacy and tolerability of
      clodronate (Leiras, Finland) in corticosteroid-induced bone loss among asthmatic
      patients. Seventy-four adult patients (41 women and 33 men, mean age 57.3 years)
      having a long history (mean 8.1 years) of oral and inhaled corticosteroid therapy
      were randomized to four parallel treatment groups: clodronate 800, 1600, or 2400
      mg/day, or an identical placebo. The bone mineral density (BMD) of the lumbar
      spine (L2-4), femoral neck, and trochanter were assessed using dual-energy X-ray
      absortiometry at entry, 6 months, and 12 months. The baseline BMDs did not differ
      significantly between the study groups. In the lumbar spine, the mean BMD
      increased significantly between the baseline and 12-month visit in the clodronate
      groups of 1600 and 2400 mg/day, 2.6% (0.02 g/cm2, p < 0.02) and 3.0% (0.03 g/cm2,
      p < 0.01), respectively, but not in the placebo and clodronate 800 mg/day groups.
      The test for a linear trend (BMD percent change for L2-4) at 12 months was
      significant (p < 0.02), indicating a dose response to clodronate. The mean BMD
      values of the femoral neck increased significantly in the 2400 mg/day group, 4.3%
      (0.03 g/cm2, p < 0.0001), as well as in the trochanter region 2.8% (0.02 g/cm2, p
      < 0.02). Gastric irritation was the most common adverse effect noted on a
      clodronate dose of 2400 mg/day. We conclude that oral clodronate is effective in
      preventing bone loss or increasing bone mass in asthmatic patients having a long
      history of continuous peroral and inhaled corticosteroid administration.

PMID- 9600796
TI  - Proceedings of the International Conference on Human Health Effects of Mercury
      Exposure. Torshavn, Faroe Islands, 24-27 June 1997.

PMID- 9600797
TI  - Mercury levels along the food chain and risk for exposed populations.
AB  - Mercury was not regarded as a pollutant of primary importance until many deaths
      due to mercury poisoning occurred in the 1950s. More recently, adverse health
      effects have been documented at relatively low exposure levels, and monitoring
      data must now be interpreted in this light. The Mediterranean basin has been
      studied in great detail over the past 20 years because of the anomalous natural
      presence of mercury. Marine animals of this basin have higher mercury body
      burdens than the same (or similar) species in the Atlantic. The mercury found in
      marine organisms is mainly in the form of methyl mercury. Long-term and frequent
      intake of seafood with high mercury levels by populations living in coastal
      fishing villages is associated with a toxic risk, especially in pregnant women.
      High blood and hair concentrations of mercury have repeatedly been found in
      fishermen of Tyrrhenian coastal villages. In some cases these concentrations have
      been associated with an increase in DNA damage in blood cells. High mercury
      levels in hair and blood of people from a fishing village of Madeira have also
      been found. This information deserves renewed scrutiny with regard to preventive
      efforts needed.

PMID- 9600798
TI  - Gold mining as a source of mercury exposure in the Brazilian Amazon.
AB  - Amalgamation has been used for more than 4500 years in mining processes. Mercury
      has been extensively used in South America by Spanish colonizers for precious
      metal recovery. It is estimated that between 1550 and 1880, nearly 200,000 metric
      tonnes of mercury was released to the environment. During the present gold rush,
      Brazil is first in South America and second in the world in gold production (with
      90% coming from informal mining or garimpos). At least 2000 tonnes of mercury has
      been released to the environment in the present gold rush. From the mid 1980s,
      environmental research has been carried out in impacted Amazon rivers, later
      followed by human exposure studies. The river basins studied were the Tapajos,
      Madeira, and Negro, but also some man-made reservoirs and areas in central
      Brazil. The analyses mainly involved sediments, soil, air, fish, human hair, and
      urine. The results show high variability, perhaps related to biological
      diversity, biogeochemical differences in the river basins, and seasonal changes.
      High mercury values also occur in some areas with no known history of gold
      mining. The results available document a considerable impact on environmental
      mercury concentrations and frequent occurrence of human exposure levels that may
      lead to adverse health effects.

PMID- 9600799
TI  - Longitudinal hair mercury concentration in riverside mothers along the Upper
      Madeira river (Brazil).
AB  - Mercury releases from gold mining occurred during the 1980s in the Upper Madeira
      river, a Southern tributary of the Amazon. Downstream from these areas, riverside
      residents rely on fish consumption for subsistence. In July of 1993, hair samples
      were collected for mercury analysis from a group of mothers and their infants and
      one pregnant woman. By assuming a constant rate of hair growth (1.1 cm per
      month), a temporal profile of the methylmercury exposure was determined for the
      previous 2 to 3 years. The length of hair segments corresponded to hair growth
      during pregnancy and the subsequent breastfeeding periods. During all periods,
      hair mercury concentrations in six mothers were in the range of 4.5-26.8 ppm,
      slightly lower than those of their infants (8.2-28.4 ppm). Further segmental
      analyses of hair mercury from another six mothers showed concentrations in the
      range of 12.2-41.0 ppm during the three trimesters of pregnancy and 4.0-33.5 ppm
      during breast feeding-slightly lower than their infants (11.6-50.4 ppm). Another
      four mothers showed hair mercury concentrations in the range of 21. 3-84.4 ppm.

PMID- 9600800
TI  - Methylmercury in fish and hair samples from the Balbina Feservoir, Brazilian
      Amazon.
AB  - The present study aimed to evaluate methylmercury in fish and human hair samples
      from an important hydroelectrical reservoir, Balbina (Brazil, Amazon). It
      presents a quite intense fishing activity and there is no known goldmining
      activity in its watershed. Fish and human hair were analyzed with a new
      extraction technique and measured by GC-ECD. Analytical quality was checked
      through intercomparisons between two laboratories with local samples and
      certified standards from IAEA. Methylmercury in hair ranged from 2.0 to 21.6
      microg . g-1 with a mean of 8.76+/-5.20 microg . g-1 (N=20), while the
      methylmercury percentages were above 90. Fish presented methylmercury levels
      ranging from 0.03 to 0.9 microg small middle dot g-1 wet wt with a mean of 0.24+/
      0.18 microg small middle dot g-1 wet wt (N=32), which is below the limit
      established for food by Brazilian legislation (0.5 microg small middle dot g-1
      wet wt) and methylmercury mean percentages were above 95%. The total mean daily
      methylmercury intake ranged from 11 to 55 microg for 70% of the sampled
      population from the village based on a daily consumption of about 110 g of fish
      with methylmercury concentrations in the range of 0.1 to 0.5 microg . g-1. This
      calculation is consistent with methylmercury concentrations in hair samples in
      the range of 2.6 to 13.1 microg . g-1.

PMID- 9600801
TI  - Mercury exposure of maroon workers in the small scale gold mining in Suriname.
AB  - Suriname is experiencing a revival of small scale gold mining activities, with
      about 10,000 to 15,000 workers involved in 1996. The estimated production in 1995
      is at least 10,000 kg crude gold. Gold is extracted with mercury and methods used
      are comparable with those described for gold mining in the Amazon Basin. Since no
      data exist on the internal mercury exposure of workers in Suriname a study was
      performed. A group of mercury-exposed Maroons, who are principally involved in
      the mining located in the tropical rainforest, is compared with nonexposed
      Maroons living in a non-gold mining area. Blood and urine samples of both groups
      were analyzed for total mercury using an atomic absorption spectrometer with an
      FIAS hydride system. In the study 28 exposed and 17 controls with a comparable
      mean age (P=0.544; exposed 27+/-7.2 years, n=26; controls 26+/-7.7 years, n=17),
      all males, participated. The urine levels for both groups differ statistically
      significantly from each other (P<0.001; exposed mean 27.5+/-21.1 microg/g
      creatinine; controls mean 5. 2+/-2.9 microg/g creatinine). This is, however, not
      the case with the blood levels (P=0.036: exposed mean 18.1+/-11.0 microg/L, n=25;
      controls mean 26.8+/-14.6 microg/L, n=16). In contrast with blood the urine total
      mercury levels in this study confirm, on a group basis, exposure to mercury as
      described for individuals working in the gold mining in the Amazon Basin.

PMID- 9600802
TI  - Methylmercury dose estimation from umbilical cord concentrations in patients with
      Minamata disease.
AB  - The methylmercury exposure of patients with congenital or infantile Minamata
      disease is known only from a small number of analyses of umbilical cords. Four
      laboratories in Japan have analyzed a total of 176 samples of umbilical cord
      tissue obtained from Minamata. The highest concentrations were seen in cord
      tissue from children born during 1950-1965, i.e., the peak period of acetaldehyde
      production in Minamata before installation of waste water treatment. Twenty-four
      samples from patients diagnosed with Minamata disease showed a median mercury
      concentration of 1.63 microg/g and differed significantly from levels seen in
      cord tissue from control children. However, children diagnosed with mental
      retardation had mercury concentrations in cord that were intermediate between the
      two other groups. Using regression coefficients obtained at a study conducted at
      the Faroe Islands, the median cord mercury concentration from the children with
      Minamata disease is estimated to correspond to about 216 microg/L cord blood and
      41 microg/g in maternal hair. Based on correlations reported in the literature,
      the median daily mercury intake of the women whose children developed Minamata
      disease can then be estimated at about 225 microg. Although these children had
      fully developed Minamata disease, the estimates of median mercury levels are only
      four to five times higher than current mercury exposure limits.

PMID- 9600803
TI  - Blood levels of total and organic mercury in residents of the upper St. Lawrence
      River basin, Quebec: association with age, gender, and fish consumption.
AB  - Increased consumption of lake fish was associated with higher blood mercury
      concentrations among 289 residents of Southwest Quebec living on the southern
      bank of the Upper St. Lawrence River System. This increase in blood mercury was
      reflected in the organic fraction and to a lesser extent with total blood
      mercury. Repeat analyses on a small subpopulation showed a correlation
      coefficient between time 1 and time 2 of approximately 0.7 for total mercury and
      for organic mercury. With one exception, blood total mercury concentrations were
      less than 5 ppb. Blood mercury concentrations were higher among men than women.
      One individual had much higher total mercury concentrations in blood (i.e., 70
      ppb) which were attributed to fish consumption based on medical and dietary
      history. The values for these subjects are compared with other North American
      data on blood mercury levels.

PMID- 9600804
TI  - Systemic transfer of mercury from amalgam fillings before and after cessation of
      emission.
AB  - In 29 volunteers with a low amalgam load, the number of amalgam-covered tooth
      surfaces and the occlusal area of the fillings were determined. Concentrations of
      total mercury were measured in plasma and erythrocytes as well as in urine
      together with the excretion rate. Absorbed daily doses were estimated from
      intraoral Hg emission by two separate methods. The transfer of Hg from the
      fillings via the oral cavity and blood to urinary excretion was evaluated
      according to the most representative combination of parameters. This consisted of
      urinary excretion (1), Hg concentration in plasma (2), absorbed dose (3), and
      occlusal area (4). Pairwise correlation coefficients were 0.75 for parameters 1
      vs 2 and 2 vs 3 and 0.49 for parameters 3 vs 4. Within 9 days after removal of
      the fillings, a transient increase was observed in plasma Hg levels only. This
      was reduced in those volunteers to whom a rubber dam had been applied during
      removal. Peak plasma Hg was 0.6 ng/ml on average and decreased with halftimes
      between 5 and 13 days. A significant decrease in Hg excretion was noted not
      before 100 days after removal. Being relatively insensitive to dietary mercury,
      the determination of total mercury in plasma and of its urinary excretion rate
      appears, under practical aspects, most suitable for the investigation of Hg
      uptake from amalgam.

PMID- 9600805
TI  - The mercury concentration in breast milk resulting from amalgam fillings and
      dietary habits.
AB  - Health risks from amalgam fillings are a subject of controversy. In Germany it is
      not advised to use amalgam fillings during breast feeding. Objectives of this
      study were to examine the concentration of mercury in human breast milk and the
      confounders which may modify the mercury levels. Women who gave birth between
      August 1995 and May 1996 in a district hospital were asked to participate in the
      study. The examination included a standardized anamnesis and an inspection of the
      teeth by an dentist. Blood and urine samples of 147 women and breast milk samples
      of 118 women were collected in the first week after birth. After 2 months of
      breast feeding a second breast milk sample was collected from 85 of women.
      Mercury was measured by cold-vapor atomic absorption spectrometry. The
      concentration of mercury in the breast milk collected immediately after birth
      showed a significant association with the number of amalgam fillings as well as
      with the frequency of meals. Urine mercury concentrations correlated with the
      number of amalgam fillings and amalgam surfaces. In the breast milk after 2
      months of lactation, the concentrations were lower (mean: <0.25 microg/L; range
      <0.25-11.7 microg/L) compared with the first sample (mean: 0.90 microg/L; range
      <0.25-20. 3 microg/L) and were positively associated with the fish consumption
      but no longer with the number of the amalgam fillings. Accordingly, the
      additional exposure to mercury of breast-fed babies from maternal amalgam
      fillings is of minor importance compared to maternal fish consumption.

PMID- 9600806
TI  - Uptake of inorganic mercury in the olfactory bulbs via olfactory pathways in
      rats.
AB  - Uptake and transport in the olfactory neurons may be an important means by which
      some heavy metals gain access to the brain. In the present study we explored
      whether inorganic mercury (203Hg2+) may be taken up in the CNS via the olfactory
      pathway. Autoradiography and gamma spectrometry showed that intranasal
      instillation of 203Hg2+ in the right nostrils of rats resulted in much higher
      levels of the metal in the right olfactory bulbs than in the left ones. At the
      side of the application of the 203Hg2+ there was also a labeling of the olfactory
      nerve bundles projecting to the olfactory bulbs as well as in the olfactory nerve
      fibres constituting the olfactory nerve layer of the bulbs, which was not seen on
      the opposite side. The results also showed that the 203Hg2+ accumulated in the
      glomerular layer of the bulbs. These data indicate that our results can be
      ascribed to a movement of the mercury along the olfactory axons to their terminal
      parts in the glomeruli and not to circulatory uptake from the mucosal
      vasculature. At late survival intervals a low labeling was also discernable in
      the external plexiform layer, indicating that a low level of 203Hg2+ leaves the
      terminal arborizations of the axons in the glomeruli. An uptake of 203Hg2+ in the
      glomerular layer of the olfactory bulbs was also seen in rats given the metal
      intraperitoneally. This uptake was similar in the right and left bulbs and always
      much lower than in the right bulbs of the rats given 203Hg2+ in the right
      nostrils. The intraperitoneal injections in addition resulted in an uptake of the
      203Hg2+ in the olfactory epithelium. We propose that in these rats the mercury is
      taken up from the blood into the olfactory neurons and then moves along the axons
      to their terminations in the olfactory bulbs. In humans a continuous exposure of
      the nasal cavity to mercury vapor (Hg0), released from amalgam fillings and
      oxidized to Hg2+ in the olfactory mucosa, as well as a potential uptake of Hg2+
      in the olfactory neurons from the blood, may lead to considerable concentrations
      of the metal in the olfactory bulbs.

PMID- 9600807
TI  - The effect of toxicokinetics on murine mercury-induced autoimmunity.
AB  - Mercury induces autoantibodies to the nucleolar protein fibrillarin (ANoA) in
      genetically susceptible (H-2AS) mouse strains. This study examines the importance
      of mercury toxicokinetics for the induction and strength (titer) of these
      autoantibodies. Female mice of the inbred strains A.SW and B10.S (H-2AS on the A
      and C57BL/10 genetic background, respectively) and A.TL and B10.TL (H-2Ak on the
      A and C57BL/10 background) were treated with 203HgCl2 in a dose of 1, 5, or 16 mg
      Hg/L drinking water for 56-70 days. Whole-body retention of 203Hg was monitored
      throughout the experimental period. Mercury accumulation in kidney, liver, heart,
      spleen, and brain was determined at end of the experiment when blood samples were
      also obtained for determination of ANoA. The drinking water consumption showed a
      limited variation between the strains and the dose groups. Therefore, intake of
      mercury did not vary much between the strains at a given dose level. The whole
      body retention of mercury reached steady state after 4-5 weeks. In general, the
      B10.S and B10.TL strains showed a lower whole-body retention and deposition of
      mercury in the kidney and the liver, compared with the A.SW and A.TL strains
      given the same dose of mercury. The B10.S strain showed a threshold for induction
      of ANoA at 5 mg Hg/L, whereas ANoA were still seen in A.SW mice given 1 mg Hg/L.
      Taken together, this is compatible with a less efficient elimination of mercury
      in the A.SW and A.TL strains, which was also supported by the higher ratio
      between whole-body retention and intake of mercury in these strains. These
      findings indicate that genes residing outside the H-2 (MHC) complex play an
      important role for regulating mercury toxicokinetics, the A genes conferring
      higher accumulation of mercury in the body than the B10 genes. In mice congenic
      with regard to the susceptible H-2AS haplotype, a highly significant correlation
      (P<0.01) existed between on the one hand the whole-body retention and organ
      accumulation of mercury and on the other hand the titer of ANoA. We conclude that
      mercury toxicokinetics differs significantly among inbred mouse strains. The
      differences in toxicokinetics are regulated by non-H-2 genes and correlate with
      the autoimmune response in the genetically susceptible strains: quantitatively as
      the titer of the ANoA and qualitatively as different threshold doses for
      induction of ANoA by mercury.

PMID- 9600808
TI  - Low-level methylmercury exposure causes human T-cells to undergo apoptosis:
      evidence of mitochondrial dysfunction.
AB  - There is growing evidence that heavy metals, in general, and mercurial compounds,
      in particular, are immunotoxic to the human immune system. The major focus of our
      study is to demonstrate that methylmercuric chloride (MeHgCl) kills human
      lymphocytes by inducing apoptosis. T-cells exposed to 0.6-5 microM MeHgCl for 24
      h were analyzed by flow cytometry. Methylmercury-treated cells exhibited
      increased Hoechst 33258 fluorescence while maintaining their ability to exclude
      the vital stain 7-aminoactinomycin. Furthermore, T-cells exposed to methylmercury
      exhibited changes in light scatter patterns that included decreased forward light
      scatter and increased side light scatter. The light scatter and fluorescent
      changes were consistent with morphological alterations displayed by cells during
      apoptosis. Cell death was further evaluated by assessing annexin V binding to the
      plasma membrane. Methylmercury-treated cells exhibited increased annexin V
      binding indicative of phosphatidylserine translocation to the outer leaflet of
      the plasma membrane. Using the fluorescent probe DiOC6(3), we noted that
      methylmercury exposure resulted in a decrease in mitochondrial transmembrane
      potential (Psim). Since a low Psim is associated with altered mitochondrial
      function, we also determined if exposure to methylmercury potentiated reactive
      oxygen species (ROS) generation. We noted that treated cells generated ROS, as
      evidenced by oxidation of hydroethidine and the generation of the fluorescent
      product, ethidium. Finally, we evaluated the effect of methylmercury on T-cell
      GSH content utilizing the fluorescent probe monochlorobimane; in the presence of
      MeHgCl, there is a marked loss in reduced cell thiols. The results of the study
      indicate that a key event in the induction of T-cell apoptosis by mercuric
      compounds is depletion in the thiol reserve which predisposes cells to ROS damage
      and at the same time activates death signaling pathways.

PMID- 9600809
TI  - The present mercury contents of scalp hair and clinical symptoms in inhabitants
      of the Minamata area.
AB  - A total of 191 fishermen and their family (32-82 years) living in some mercury
      polluted areas along the Shiranui Sea volunteered for the present study. They
      made a living by fishery and had formerly eaten the methyl mercury-contaminated
      fish and shellfish caught there. The questionnaire on subjective symptoms, fish
      eating habits, and past living history was conducted on the subjects. In
      addition, they were clinically examined in detail by several neurologists and
      scalp hair was collected. With six exceptions, all the 185 subjects showed a
      normal total mercury level in hair (<10 ppm). The ratio of methyl mercury to
      total mercury was 79-94% on the average for each group examined, suggesting
      indirect contamination (perhaps through the food chain). Despite their low
      mercury level in scalp hair, however, the subjects showed various neurological
      symptoms, particularly, sensory disturbance (such as the glove and stocking
      type), at a very high rate. Thus, it seems fair to state that, in addition to
      officially recognized Minamata disease patients, there still exist many people
      with atypical, slight Minamata disease on the coast of the Shiranui Sea. The
      current hair mercury level is not necessarily useful as a criterion for
      diagnosing chronic Minamata disease because of the long lapse of time.

PMID- 9600810
TI  - Cognitive performance of children prenatally exposed to "safe" levels of
      methylmercury.
AB  - Within a cohort of 1022 consecutive singleton births in the Faroe Islands, we
      assessed prenatal methylmercury exposure from the maternal hair mercury
      concentration. At approximately 7 years of age, 917 of the children underwent
      detailed neurobehavioral examination. Little risk is thought to occur as long as
      the hair mercury concentration in pregnant women is kept below 10-20 microg/g (50
      100 nmol/l). A case group of 112 children whose mothers had a hair mercury
      concentration of 10-20 microg/g was therefore matched to children with exposure
      below 3 microg/g, using age, sex, time of examination, and the mother's score on
      Raven's Progressive Matrices as matching criteria. The two groups were almost
      identical with regard to other factors that might affect neurobehavioral
      performance in this community. On six neuropsychological test measures, the case
      group showed mild decrements, relative to controls, especially in the domains of
      motor function, language, and memory. Subtle effects on brain function therefore
      seem to be detectable at prenatal methylmercury exposure levels currently
      considered to be safe.

PMID- 9600811
TI  - Reversible color vision loss in occupational exposure to metallic mercury.
AB  - Color vision was evaluated in twenty-one mercury exposed workers and referents
      matched for sex, age, tobacco smoking, and alcohol habits. The Lanthony 15 Hue
      desaturated panel (D-15 d) was applied. In the workers, mean urinary Hg (HgU) was
      115+/-61.5 microg/g creatinine; in all but one the values exceeded the biological
      limit (BEI) proposed by the American Conference of Governmental Industrial
      Hygienists. A dose-related subclinical color vision impairment was observed in Hg
      exposed workers compared to the referents. Just after the survey, working
      conditions were improved. Twelve months later the workers were reexamined. Mean
      HgU was 10.0 microg/g creatinine and in no subjects was the BEI exceeded. Color
      perception was significantly improved compared to the first examination and,
      furthermore, no differences were observed between exposed workers and referents.
      The results add evidence that the color vision loss observed during the first
      part of the study was related to Hg exposure and, moreover, show that this effect
      is reversible. These data indicate that metallic Hg can induce a reversible
      impairment in color perception. This suggests that color vision testing should be
      included in studies on the early effects of Hg. The possibility of applying the D
      15 d as an early effect index in the biological monitoring of Hg exposed workers
      should also be entertained.

PMID- 9600812
TI  - "Recurrence within 6 months of platinum therapy": an adequate definition of
      "platinum-refractory" ovarian cancer?

PMID- 9600813
TI  - The role of operative laparoscopy to evaluate candidates for pelvic exenteration.

PMID- 9600814
TI  - Operative laparoscopy prior to a pelvic exenteration in patients with recurrent
      cervical cancer.
AB  - INTRODUCTION: Selecting out the true candidates for a pelvic exenteration
      frequently poses a difficult clinical dilemma in patients with recurrent cervical
      cancer after radiation therapy. Despite very thorough preoperative investigation,
      inoperable disease is discovered at the time of laparotomy in up to 60% of cases.
      SUBJECTS AND METHODS: In this retrospective analysis, we report the use of
      operative laparoscopy in 13 patients with either biopsy proven locally recurrent
      cervical cancer (N = 9) or with clinically suspected tumor recurrence (N = 4).
      All have previously received radical radiation therapy. RESULTS: Patients' ages
      ranged from 36 to 79 years (median, 43). The median duration of the procedure was
      150 min (range,50-200) and median blood loss was 50 cc (range, 50-200). The
      procedure was well tolerated in all patients. There was no intraoperative
      complication. One deep thrombophlebitis occurred postoperatively. The
      laparoscopic evaluation could not be completed in one case because of a large
      nonmobile uterine fibroid filling the whole pelvis. At laparoscopy, metastatic
      tumor was identified in 9 of 12 patients (75%). An unnecessary laparotomy was
      avoided in 8 of those 9 cases (one had a palliative exenteration). The most
      common site of metastasis was in the previously radiated pelvis (7/9). Three
      patients had a negative laparoscopy. Two had an exenteration and one had a
      transureteroureterostomy. At the time of laparotomy, none were found to have
      disease that would have been missed at laparoscopy. CONCLUSION: We conclude that
      operative laparoscopy may be a valuable additional step in the work-up and
      management of patients with locally recurrent cervical cancer. With experience in
      retroperitoneal surgery, the procedure can be carried out safely in previously
      radiated patients. We believe this approach can lower the number of unnecessary
      laparotomies, reduce the morbidity, and shorten the length of the postoperative
      recovery.

PMID- 9600815
TI  - Complete cytoreductive surgery is feasible and maximizes survival in patients
      with advanced epithelial ovarian cancer: a prospective study.
AB  - OBJECTIVE: Despite correlation between the completeness of surgical cytoreduction
      and survival for patients with advanced ovarian cancer, relatively few undergo
      complete cytoreduction. This study was initiated to prospectively determine the
      ability to surgically eliminate all visible disease in patients with stage IIIC
      and IV epithelial ovarian cancer and the associated impact on survival. METHODS:
      Between 1990 and 1996, 163 consecutive patients underwent primary cytoreduction.
      The goal was the excision or ablation of all visible disease prior to initiation
      of systemic platinum-based combination chemotherapy. A multivariate analysis
      determined which clinical and pathologic variables influenced the probability of
      achieving complete cytoreduction (logistic regression) and survival (Cox
      proportional hazards model). RESULTS: One hundred thirty-nine patients (85.3%)
      underwent removal of all visible tumor, 22 (13.5%) had cytoreduction to </=1 cm
      residual disease, and 2 (1.2%) had unresected bulky disease. The median and
      estimated 5-year survival for the entire cohort was 54 months and 48%,
      respectively. The probability of achieving complete cytoreduction was influenced
      independently by the preoperative Gynecologic Oncology Group performance status
      (0-1 vs 2-3, P = 0.04), the number of mesenteric and intestinal serosal implants
      (</=75 vs >75 implants, P = 0.005), and stage (IIIC vs IV, P = 0.006). The
      probability of survival was independently influenced by age (</=61 vs >61 years,
      P = 0.003), volume of ascites (</=1 vs >1 liter, P = 0.01), stage (IIIC vs IV, P
      = 0.04), histology (clear cell and mucinous vs all other, P = 0.03), and the
      completeness of cytoreductive operation (complete vs incomplete cytoreduction, P
      = 0.02). CONCLUSIONS: Complete cytoreduction is possible for the majority of
      patients and improves survival, even compared to operations with minimal (</=1
      cm) residual disease. Unless their medical condition prohibits anesthesia and
      surgery, patients with advanced epithelial ovarian cancer should undergo primary
      cytoreductive surgery with the intention of complete tumor removal.

PMID- 9600816
TI  - Adequacy of screening cervical cytology among human immunodeficiency virus
      seropositive women.
AB  - OBJECTIVE: To evaluate the adequacy of cytology in detecting cervical
      intraepithelial neoplasia (CIN) among human immunodeficiency virus (HIV)
      seropositive women compared to controls. METHODS: A cross-sectional study was
      carried out evaluating 241 HIV-seropositive women and 991 controls (404 HIV
      seronegative and 587 of unknown HIV status) at risk for CIN attending a vaginitis
      clinic. All patients had a Pap smear and a standard colposcopic examination of
      the lower genital tract. Cervical biopsies were taken as indicated by colposcopy.
      Cytology and histology slides were read by a cytopathologist blinded to patients'
      serostatus. False-negative cytologic cases were reviewed by three independent
      cytopathologists to estimate sampling and screening error rates. Sensitivity,
      specificity, and false-negative rate of cytologic smears were compared between
      HIV seropositives and controls. We estimated the sampling and screening error
      rates among cases with false-negative cytology. RESULTS: Among seropositives, the
      sensitivity, specificity, and the false-negative smear rate for CIN were 73.4%
      (47/64), 97.1% (134/138), and 26.6% (17/64), respectively. The corresponding
      figures in controls were 83.8% (83/99), 99.04% (825/833), and 16.2% (16/99),
      respectively, and did not differ significantly from those of seropositives. The
      negative predictive value of cytology was lower among seropositives (134/151)
      than in controls (825/841, chi2 = 34.8, P < .001). The agreement between
      cytologic readings and combined colposcopy and histology was stronger among
      controls (kappa = 0.789, 95% CI 0.723 to 0.856) than among seropositives (kappa =
      0. 593, 95% CI 0.475 to 0.712). Three independent cytopathologists were unable to
      detect atypical cells in 52.9% (9/17) of false-negative smears taken from
      seropositive women as opposed to 37.5% (6/16) of controls. CONCLUSIONS: The
      sensitivity, specificity, and false negative rate of screening cytology for CIN
      among HIV seropositive women are comparable with those in the general population.
      Since almost 50% of false-negative results could be attributed to sampling
      errors, more frequent cytological screening may prove to be beneficial to this
      high-risk group.

PMID- 9600817
TI  - Detection of human papillomavirus type 16 E6/E7 oncogene transcripts in
      dysplastic and nondysplastic cervical scrapes by nested RT-PCR.
AB  - Infections with high-risk human papillomaviruses (e.g., HPV-16) play an important
      role in the development of cervical intraepithelial neoplasia (CIN) and invasive
      cervical cancer (IC). Continued expression of the viral E6 and E7 genes is
      believed to be a key factor for oncogenic transformation of infected cells. Two
      spliced transcripts of the E6/E7 oncogenes, termed E6*I and E6*II, can be
      detected by reverse transcriptase polymerase chain reaction (RT-PCR). To increase
      the sensitivity of detecting E6/E7 transcripts in cervical scrapes we took
      advantage of a nested RT-PCR (nRT-PCR) protocol. In a series of 30 HPV-16
      positive patients with histologic diagnoses ranging from nondysplastic epithelium
      to IC, the application of nRT-PCR significantly improved the detection of E6/E7
      transcripts compared to conventional RT-PCR. The prevalence of E6/E7 spliced
      transcripts correlated with lesion severity and the nRT-PCR protocol allowed
      detection of these transcripts even in nondysplastic epithelium and CIN I
      lesions. Therefore, in epidemiologic follow-up studies, detection of E6/E7
      transcripts by nRT-PCR should prove to be a useful diagnostic tool for risk
      evaluations regarding the development of CIN and its progression to cervical
      cancer, especially in high-risk HPV-type-infected patients with CIN 0 and CIN I.

PMID- 9600818
TI  - Single-dose dexamethasone paclitaxel premedication.
AB  - Paclitaxel is one of the most active chemotherapy agents for the treatment of
      ovarian and other gynecologic cancers. Hypersensitivity reactions (HSR) remain
      one of the major clinical concerns in the use of paclitaxel. This report deals
      with 183 consecutive patients treated with paclitaxel chemotherapy. A total of
      1010 cycles were administered. Premedication consisted of single-dose intravenous
      decadron, benadryl, and cimetidine administered immediately prior to
      chemotherapy. Four hypersensitivity reactions occurred. All patients recovered
      uneventfully from these reactions. Two of these patients received additional oral
      decadron followed by the standard premedication and were successfully retreated
      with multiple courses of paclitaxel therapy without reaction. Our findings
      confirm other reports that paclitaxel chemotherapy hypersensitivity reactions can
      be decreased with a single-dose intravenous decadron premedication regimen and
      that patients who do have paclitaxel HSRs may be safely retreated with
      paclitaxel.

PMID- 9600819
TI  - Treatment of late recurrent vaginal malignancy after initial radiotherapy for
      carcinoma of the cervix: an analysis of 73 cases.
AB  - PURPOSE: To evaluate the reirradiation therapy in late recurrent vaginal
      malignancy after initial radiotherapy for carcinoma of the cervix. METHODS: From
      July 1972 to July 1992, 73 cases of late recurrent (over 5 years) vaginal
      malignancy after initial radiotherapy for cervical cancer were treated in our
      hospital. Both the original and recurrent cancers were biopsy-proven squamous
      cell carcinoma. All of these patients received reirradiation therapy;
      chemotherapy or operation was combined when necessary. The reirradiation was
      planned according to the site and volume of the recurrent tumor, previous
      radiation dose, and radiation side effects. Brachytherapy was mainly used. Before
      1981, radium therapy was delivered at 30-40 Gy in 3-5 fractions to tumor base
      within 3-4 weeks. High-dose-rate (100 cGy/min) cobalt-60 afterloading therapy
      (Ralstron therapy) has been used instead of radium since 1981; the dose to the
      tumor base was 20-35 Gy/3-5 fractions/3-4 weeks. Then, vaginal mold was
      supplemented with a dose to a point 0.5 cm below the surface of the vaginal
      mucosa at 20-30 Gy/4-6 fractions/2-3 weeks. When the vulva or groin was involved,
      cobalt-60 or high-energy electron beam radiation was added with a dose at 30-40
      Gy. Among these, 61 patients received irradiation therapy alone. Eleven patients
      received irradiation combined with chemotherapy. One patient received
      hysterectomy after reirradiation. RESULTS: The 2-, 3-, and 5-year survival rates
      in this series were 54.7% (40/73), 46. 6% (28/60), and 40.3% (21/52),
      respectively. The 5-year survival rates for upper, upper-middle, and upper-lower
      vaginal tumor were 81. 8% (9/11), 33.3% (5/15), and 25.0% (3/12), respectively.
      The effect for upper vaginal recurrent malignancy was remarkably better than that
      for the upper-lower rate (P < 0.05). The local control rates for tumor >4 and <4
      cm were 26.6% (4/15) and 86.5% (32/37), respectively (P < 0.01). The side effects
      of reirradiation in this series were serious: both moderate and severe radiation
      reactions were rectum 13.6% (10/73), hematuria 12.3% (9/73), vesicovaginal
      fistula 1.4% (1/73), and rectum-vaginal fistula 11.0% (8/73). CONCLUSIONS: We
      conclude that reirradiation for late recurrence in the vagina after previous
      radiotherapy for cervical cancer is valuable. Early detection and treatment could
      achieve better results. The smaller the recurrent tumor volume, the better the
      treatment effects. Reirradiation therapy should be carefully managed in order to
      reduce the complications as much as possible.

PMID- 9600821
TI  - A randomized trial of standard versus partially hyperfractionated radiation with
      or without concurrent 5-fluorouracil in locally advanced cervical cancer.
AB  - The objective of this study was to determine whether the addition of concurrent 5
      fluorouracil (5-FU) and/or a change in radiation fractionation improves pelvic
      control and survival or decreases complications in advanced cervical cancer, FIGO
      stages IB/IIA (>=5 cm) to IVA inclusive. After stratification by pelvic disease
      extent, 234 of a planned 292 patients were randomized to receive one of four
      possible treatments: (a) standard external beam pelvic irradiation (RT) 5000 cGy
      in 25 fractions versus (b) RT as in arm (a) with infusional IV 5-FU 1g/m2 daily
      in the first and last 4 days of RT, (c) partially hyperfractionated RT, 5280 cGy
      in 33 fractions, two fractions per day on the first and last 4 days of RT, or (d)
      arm (c) with the same FU. All were followed with a linear source of intracavitary
      RT to deliver 40 Gy. The median duration of follow-up for the 221 evaluable
      patients was 59 months. The 5-year Kaplan-Meier disease-free survival (DFS) in
      arm (a), (c), (d), and (b), respectively, were 45, 53, 58, and 61%. The
      differences in survival and pelvic control were not statistically significant. An
      exploratory subset analysis was performed within stratum 1 and stratum 2 to
      generate hypotheses for future studies. Only for the 99 patients in stratum 1
      (IB/IIA or medial parametrial IIB disease) was the 5-year DFS significantly
      better (long rank P = 0.05) for standard RT and 5-FU. The DFS was 39% for arm
      (a), 76% for arm (b), 58% for arm (c), and 65% for arm (d). A multivariate
      analysis of patient, tumor, and treatment related prognostic factors identified
      only the use of 5-FU to account for the observed difference. The crude serious
      late bowel or bladder complication rate was 5.9%. Overall concurrent infusional 5
      FU was not beneficial when added to standard RT in this study. The possible
      benefit for patients in stratum 1 requires exploration in a further randomized
      trial with appropriate accrual.

PMID- 9600820
TI  - Neoadjuvant intraarterial chemotherapy followed by radical hysterectomy and/or
      radiotherapy for locally advanced cervical cancer.
AB  - OBJECTIVES: We assessed neoadjuvant intraarterial chemotherapy (NAC) followed by
      radical hysterectomy and/or radiotherapy in patients with locally advanced
      cervical cancer. METHODS: Over 5 years, 48 consecutive women with International
      Federation of Gynecology and Obstetrics stage IIb-IVa cervical cancer were
      enrolled. Treatment consisted of bilateral internal iliac artery infusion of
      cisplatin (100 mg/m2, day 1) or carboplatin (400 mg/m2, day 1) and peplomycin (20
      mg/m2, day 1) for two courses separated by 3 weeks. Doxorubicin (30 mg/m2, day 1)
      was added for patients with adenocarcinoma. Stage III patients who responded to
      NAC and Stage IIb patients underwent radical hysterectomy with pelvic
      lymphadenectomy. Stage III patients not responding to NAC and all stage IVa
      patients were treated with pelvic radiotherapy. RESULTS: Complete response was
      achieved in 5 (10.4%) of 48 patients, while a partial response was noted in 32
      (66. 7%) and stable disease in 11 (22.9%). Of 25 patients with stage IIIb
      disease, 16 (64.0%) were able to undergo surgery. The 4-year disease-free
      survival (DFS) was 80.0% in patients with stage IIb and 62.3% in patients with
      stage III. In stage IIIb, the 4-year DFS in patients receiving surgery (75.2%)
      was higher than the DFS for those receiving radiotherapy (44.4%) (P < 0.05).
      Grade 3 or 4 leukopenia developed in 17 (35.4%) patients. Nausea and vomiting of
      grade 2 or higher occurred in 34 (70.8%). Creatinine clearance transiently
      decreased (>/= grade 2) in 16.6%. Patients negative for serum squamous cell
      carcinoma-associated antigen (SCC) responded better to NAC than to SCC-positive
      cases, and SCC-negative survival was significantly better than SCC-positive
      survival (P < 0.05). CONCLUSIONS: Neoadjuvant intraarterial chemotherapy with
      platinum was safely performed, and a survival benefit followed radical surgery
      with or without radiotherapy after response to NAC.

PMID- 9600822
TI  - Using a logistic model to predict malignancy of adnexal masses based on
      menopausal status, ultrasound morphology, and color Doppler findings.
AB  - In the present study we aimed to develop a formula for predicting adnexal
      malignancy based on menopausal status, ultrasound morphology, and color Doppler
      findings. Logistic regression analysis was performed retrospectively in 79
      adnexal masses (59 benign and 20 malignant) in 73 unselected and consecutive
      patients. All these masses had been preoperatively evaluated using transvaginal
      color Doppler ultrasonography. In logistic analysis menopausal status
      (premenopausal vs postmenopausal), color Doppler findings (no flow or lowest
      resistance index >0.45 vs lowest resistance index </=0.45) and ultrasound
      morphology (nonsuspicious vs suspicious) were entered as categorical variables.
      Morphology and color Doppler were found to be independent predictors, whereas
      menopausal status was not. To assess the validity of the developed mathematical
      formula, this was applied prospectively in a second series of 58 consecutive and
      unselected patients diagnosed of adnexal mass and scheduled for surgery. The
      probability of malignancy was estimated in each case. Overall, 56 of 58 (96.5%)
      adnexal masses were correctly classified. We conclude that the formula developed
      in this study is easy to apply and could be useful to predict malignancy or
      benignity of adnexal masses.

PMID- 9600823
TI  - Systematic pelvic and paraaortic lymphadenectomy at second-look laparotomy for
      ovarian cancer.
AB  - A retrospective review of the medical records of all ovarian cancer patients
      admitted to our institution from January 1974 to December 1993 was performed. A
      total of 58 consecutive patients who underwent systematic pelvic and paraaortic
      lymphadenectomy during second-look surgery was found. Node metastases were found
      in 15 of 58 patients (25.8%). No significant correlation was found between the
      variables of disease (e.g., stage of the disease at diagnosis, histology, grade,
      residual tumor after the first cytoreductive surgery, and the type of
      chemotherapy administered) and node status at second-look. Node metastases were
      found in 8 of 45 (17.7%) patients with absence of intraperitoneal disease,
      compared with 7 of 11 (63.6%) patients with intraabdominal residual disease (P <
      0.02). There was no difference in 5-year survival for patients with absence of
      residual tumor in the peritoneal cavity as well as in the retroperitoneum (5-year
      survival 80%) and for patients with retroperitoneal disease only (5-year survival
      77%). On the contrary, a highly significant difference in survival (P < 0.001)
      was observed between these two groups of patients and those who had
      intraabdominal residual tumor. Twelve of 45 (26.6%) patients have recurred. FIGO
      stage, grade, and residual disease after primary surgery were determinant in
      predicting recurrence. Notably, no relation emerged between relapse rate and the
      node status at second-look.

PMID- 9600824
TI  - Prognostic factors of primary adenocarcinoma of the uterine cervix.
AB  - OBJECTIVE: To determine which clinicopathological factors influence the prognosis
      of cervical adenocarcinoma. METHODS: Three hundred and two cases of primary
      adenocarcinoma of the uterine cervix, treated between 1977 and 1994, were studied
      retrospectively. Clinical data and pathological findings with respect to primary
      therapy were reviewed and evaluated. RESULTS: The 5-year survival rates for
      stages I, II, and III/IV were 75.9, 62.9, and 25.1%, respectively. International
      Federation of Gynecology and Obstetrics stage (P < 0. 0001), cell type (P =
      0.0176), tumor grade (P = 0.023), lymph node status (P = 0.018), and bulky tumor
      (P = 0.007) were found to be independent factors using the stepwise Cox
      proportional hazards model. Old age (P = 0.0581), presence of hypertension (P =
      0.46), diabetes mellitus (P = 0.18), obesity (P = 0.15), and oral contraceptive
      use (P = 0.42) were not found to adversely influence survival rates for cervical
      adenocarcinoma after adjusting for other covariates. Adenosquamous adenocarcinoma
      had a better prognosis than endocervical columnar cell adenocarcinoma in stages I
      and II (P = 0. 0235). Also, in cervical adenocarcinoma's early stages,
      multivariate modeling revealed that chances of survival were significantly better
      for patients treated by radical surgery than for patients treated by radiation
      therapy (P < 0.001). CONCLUSIONS: Survival rates for cervical adenocarcinoma were
      significantly influenced by stage, histologic subtype, tumor grade, the presence
      of a positive lymph node, and tumor size. Although a randomized prospective study
      is needed, our data imply that radical surgery may be considered a better primary
      modality of treatment than radiation therapy for the early stages of cervical
      adenocarcinoma. Further, the presence of hypertension, diabetes mellitus, or
      obesity may not adversely influence survival rates.

PMID- 9600825
TI  - Malignant melanoma metastatic to the ovary: presentation and radiological
      characteristics.
AB  - Cutaneous melanomas rarely metastasize to the ovary; however, we have recently
      encountered three cases which have proved a diagnostic dilemma. All presented
      with a pelvic mass and a past history of cutaneous melanoma but both ultrasound
      examination and CT scanning proved inconclusive and neither was able to
      accurately characterize the lesions. Magnetic resonance imaging (MRI) was able to
      demonstrate the presence of melanin in one of the ovarian lesions as peripheral
      high signal change on T1-weighted images. The two lesions without melanin failed
      to show this feature. MRI may therefore be useful in the diagnosis of ovarian
      melanoma but only if melanin is present.

PMID- 9600826
TI  - Leiomyosarcoma of the uterine cervix.
AB  - The clinicopathologic features of a patient with uterine leiomyosarcoma arising
      in the cervix are presented. A 47-year-old Japanese woman was admitted with
      complaints of hypermenorrhea and abdominal distention. A hysterectomy with
      bilateral salpingo-oophorectomy revealed a tumor weighing 10.5 kg, which was the
      largest cervical leiomyosarcoma reported in the literature. She was given eight
      courses of combination chemotherapy (VADIC and Hydroxyurea, DTIC, Etoposide) and
      is alive without evidence of recurrence 35 months after the initial therapy.

PMID- 9600827
TI  - Vaginal glomus tumor presented as a painless cystic mass.
AB  - OBJECTIVE: To present clinical and pathological findings of extremely rare
      vaginal glomus tumor. METHODS: Clinical details were obtained from patient
      records. Histopathological examination included immunohistochemistry. RESULTS: A
      45-year-old menopausal woman had a 4-year history of painless cystic mass, 1.0 cm
      in diameter, on the anterior vaginal wall. Surgical excision of mass was
      uneventful. Histological examination revealed glomus tumor, primarily solid but
      also containing a clearly identifiable angiomatous component. Tumor cells showed
      prominent cytoplasmic immunostaining for vimentin and actin and negative staining
      for desmin, epithelial membrane antigen, pancytokeratin, Factor VIII, S-100, HMB
      45, chromogranin, and estrogen, progesterone, and androgen receptors. CONCLUSION:
      Vaginal glomus tumor may be painless and, when the angiomatous component is
      evident, may appear as cystic mass.

PMID- 9600828
TI  - Profound thrombocytopenia in previously treated patients with recurrent ovarian
      carcinoma receiving topotecan.

PMID- 9600830
TI  - Reply 
AB  - Copyright

PMID- 9600829
TI  - Profound thrombocytopenia in previously treated patients with recurrent ovarian
      carcinoma receiving topotecan.

PMID- 9600831
TI  - Access to quality cancer care. Consensus statement of the American Federation of
      Clinical Oncologic Societies.

PMID- 9600833
TI  - A non-hypervariable human minisatellite strongly stimulates in vitro
      intramolecular homologous recombination.
AB  - Several features indicate that the low polymorphic human minisatellite MsH42
      region could be involved in recombination. It contains different well-known
      recombination motifs, is able to generate single-stranded loops and is
      specifically recognized by nuclear proteins. These characteristics led us to
      investigate the possible recombinogenic activity of the MsH42 region in terms of
      intramolecular recombination. We constructed two plasmids, one of them carrying
      two copies of the minisatellite region and the other one containing sequences
      upstream of this repetitive region. We showed that MsH42 strongly stimulates
      intramolecular in vitro recombination, approximately 22 times more than the
      control sequence, solely when the source of biological extract is mouse testes,
      suggesting that MsH42 could be a hotspot involved in meiotic recombination.
      Furthermore, there is a direct relationship between the frequency of equal
      crossovers and the enhancement of recombination. Interestingly, the third repeat
      of the minisatellite array is always involved in the resolution of unequal
      crossovers leading to minisatellite shortening. As far as we know, our results
      provide the first evidence that a non-hypervariable minisatellite can enhance
      homologous recombination.

PMID- 9600834
TI  - The N terminus of the flagellar switch protein, FliM, is the binding domain for
      the chemotactic response regulator, CheY.
AB  - A key event in signal transduction during chemotaxis of Salmonella typhimurium
      and related bacterial species is the interaction between the phosphorylated form
      of the response regulator CheY (CheY approximately P) and the switch of the
      flagellar motor, located at its base. The consequence of this interaction is a
      shift in the direction of flagellar rotation from the default, counterclockwise,
      to clockwise. The docking site of CheY approximately P at the switch is the
      protein FliM. The purpose of this study was to identify the CheY-binding domain
      of FliM. We cloned 17 fliM mutants, each defective in switching and having a
      point mutation at a different location, and then overexpressed and purified their
      products. The CheY-binding ability of each of the FliM mutant proteins was
      determined by chemical crosslinking. All the mutant proteins with an amino acid
      substitution at the N terminus, FliM6LI, FliM7SY and FliM10EG, bound CheY
      approximately P to a much lesser extent than did wild-type FliM. CheY
      approximately P-binding of the other mutant proteins was similar to wild-type
      FliM. To investigate whether the FliM domain that includes these three mutations
      is indeed the CheY-binding domain, we synthesized a peptide composed of the first
      16 amino acid residues of FliM, including a highly conserved region of FliM
      (residues 6 to 15). The peptide bound CheY and, to a larger extent, CheY
      approximately P. It also competed with full-length FliM on CheY approximately P.
      These results indicate that the CheY-binding domain of FliM is located at the N
      terminus, within residues 1 to 16, and suggest that FliM monomers can form a
      complete site for CheY binding.

PMID- 9600835
TI  - Two distinct pathways can control expression of the gene encoding the Drosophila
      antimicrobial peptide metchnikowin.
AB  - Metchnikowin is a recently discovered proline-rich peptide from Drosophila with
      antibacterial and antifungal properties. Like most other antimicrobial peptides
      from insects, its expression is immune-inducible. Here we present evidence that
      induction of metchnikowin gene expression can be mediated either by the TOLL
      pathway or by the imd gene product. We show that the gene remains inducible in
      Toll-deficient mutants, in which the antifungal response is blocked, as well as
      in imd mutants, which fail to mount an antibacterial response. However, in Toll
      deficient;imd double mutants, metchnikowin gene expression can no longer be
      detected after immune challenge. Our results suggest that expression of this
      peptide with dual activity can be triggered by signals generated by either
      bacterial or fungal infection. Cloning of the metchnikowin gene revealed the
      presence in the 5' flanking region of several putative cis-regulatory motifs
      characterized in the promoters of insect immune genes: namely, Rel sites, GATA
      motifs, interferon consensus response elements and NF-IL6 response elements.
      Establishment of transgenic fly lines in which the GFP reporter gene was placed
      under the control of 1.5 kb of metchnikowin gene upstream sequences indicates
      that this fragment is able to confer full immune inducibility and tissue
      specificity of expression on the transgene.

PMID- 9600836
TI  - Apo-AraC actively seeks to loop.
AB  - In the absence of arabinose and interactions with other proteins, AraC, the
      activator-repressor that regulates the araBAD operon in Escherichia coli, was
      found to prefer participating in DNA looping interactions between the two well
      separated DNA half-sites, araI1 and araO2 at their normal separation of 211 base
      pairs rather than binding to these same two half-sites when they are adjacent to
      one another. On the addition of arabinose, AraC preferred to bind to the
      adjacently located half-sites. Inverting the distally located araO2 half-site
      eliminated the looping preference. These results demonstrate that apo-AraC
      possesses an intrinsic looping preference that is eliminated by the presence of
      arabinose. We developed a method for the accurate determination of the relative
      affinities of AraC for the DNA half-sites araI1, araI2, and araO2 and non
      specific DNA. These affinities allowed accurate calculation of basal level and
      induced levels of expression from pBAD under a wide variety of natural and mutant
      conditions. The calculations independently predicted the looping preference of
      apo-AraC.

PMID- 9600837
TI  - Arm-domain interactions in AraC.
AB  - N-terminal deletions extending beyond the sixth amino acid of the Escherichia
      coli regulator of the l-arabinose operon, AraC, were found to generate
      constitutive regulatory behavior of the promoter pBAD. Mutagenesis of the DNA
      coding for the first 20 amino acids of the protein and screening for
      constitutives yielded mutants across the region whereas screening for mutants
      that cannot induce pBAD, even in the presence of arabinose, yielded none. These
      results indicate that the N-terminal arm is not essential for transcription
      activation, but that it plays an important and active role in holding the system
      in a non-activating state. Despite the fact that arabinose binds to the N
      terminal domain of AraC, mutations were found in the C-terminal domain that
      weaken the binding of arabinose to the protein. The effects of the mutations
      could be suppressed by specific mutation in the N-terminal arm or by deletion of
      the arm. These results, in conjunction with the crystal structures of the N
      terminal domain determined in the presence and absence of arabinose, indicate
      that in the absence of arabinose, the N-terminal arms of the protein bind to the
      C-terminal DNA binding domains to hold them in a state where the protein prefers
      to loop. When arabinose is added, the arms are pulled off the C-terminal domains,
      thereby releasing them to bind to adjacently located DNA half-sites and activate
      transcription.

PMID- 9600838
TI  - Operator search by mutant Lac repressors.
AB  - The Escherichia coli Lac and Gal repressors are two members of a large family of
      bacterial repressor proteins that share significant sequence and structural
      homology. Efficient repression by all family members requires specific binding to
      a site or sites close to the transcriptional start of the genes regulated. Both
      LacR and GalR have to bind to at least two sites for efficient repression, yet
      they differ in one important respect: LacR is a homotetramer whereas GalR is a
      homodimer. In an attempt to understand this difference, we studied the operator
      binding activity of a LacR variant that has the DNA-binding specificity of GalR
      (LacR-V17A18). A tetrameric version of this protein shows a 30-fold decrease in
      association rate to operator located on a long (lambda) DNA molecule, in
      comparison to wild-type LacR, while a dimeric version of this protein shows an
      unaltered association rate in comparison to dimeric LacR. This reduction in
      association rate correlates with a broadened DNA-binding specificity for base
      pairs 4 and 5 of the operator: examination of an additional LacR variant with an
      even broader DNA-binding specificity indicates that a tetrameric version also
      shows a 30-fold decrease in association rate in comparison to wild-type LacR,
      while a dimeric version again shows an unaltered association rate in comparison
      to dimeric LacR. This difference in association rate in vitro correlates with
      whether a tetrameric or dimeric variant of LacR of a given DNA-binding
      specificity will repress lacZ under control of a single operator more efficiently
      in vivo. We therefore propose that the formation of stable homotetramers becomes
      a distinct disadvantage unless a high degree of DNA-binding specificity is also
      present, and demonstrate that this in indeed the case for GalR-mediated
      repression of the gal operon. This functional constraint seems to have influenced
      the evolution of the LacI-GalR family of repressors, most of which have a
      relatively broad specificity of DNA-binding and most of which form only stable
      homodimers.

PMID- 9600839
TI  - Properties of strand displacement synthesis by Moloney murine leukemia virus
      reverse transcriptase: mechanistic implications.
AB  - Previous results indicated that Moloney murine leukemia virus reverse
      transcriptase is capable of extensive synthesis under conditions where it must
      simultaneously displace a downstream non-template DNA strand. To investigate more
      fully the mechanistic basis for displacement synthesis and to characterize the
      activity with natural viral templates, displacement and non-displacement
      synthesis were compared under a variety of conditions using the viral long
      terminal repeat plus strand as the template. Although the rates of both
      displacement and non-displacement synthesis varied regionally over the template,
      on the average, displacement synthesis was slower by a factor of approximately 3
      to 4. Surprisingly, with one particular primer situated downstream of the tRNA
      primer binding site, displacement synthesis was found to be at least tenfold more
      processive than non-displacement synthesis, approaching a value of 500
      nucleotides. The sequence features associated with pausing during the two modes
      of synthesis are different in both nucleotide preference and position relative to
      the enzyme, suggesting that the enzyme contacts the DNA differently under the two
      modes of synthesis. It was found that pausing during displacement synthesis did
      not reflect those local regions of DNA with a predicted high degree of thermal
      stability. Moreover, the very similar effects of temperature on the rates of
      displacement and non-displacement synthesis make unlikely a strictly passive
      mechanism of displacement synthesis whereby breathing of the downstream duplex is
      sufficient for advancement of the polymerase. Together, these results suggest a
      mechanism of displacement synthesis in which reverse transcriptase actively
      participates in the process of strand separation in front of the translocating
      polymerase.

PMID- 9600840
TI  - The mathematics of SELEX against complex targets.
AB  - We have developed a computer model for the simulation of simultaneous SELEX
      against multiple targets. The model assumes equilibrium behavior for the
      formation of binary ligand:target complexes, and that there is no ligand:ligand
      or target:target interaction. Target concentrations, ligand concentrations, and
      affinity distributions of the initial ligand pool for each individual target may
      be set by the user. We have used this program to gain an understanding of how the
      presence of multiple targets affects the selection process. In most cases, we
      find that SELEX is capable of generating different ligands for the different
      targets in a heterogeneous mixture, regardless of large variations in target
      concentrations and ligand:target affinities. A low relative partitioning
      efficiency (the efficiency with which ligands complexed with a target are
      separated from free ligands) for a target in a mixture gives a greatly reduced
      rate of selection of high-affinity ligands to that target. The ratio of each high
      affinity ligand to its individual target within a pool of ligands selected for
      binding against a mixture of targets is approximately proportional to the
      concentration of the target multiplied by the ligand:target partitioning
      efficiency.

PMID- 9600841
TI  - Protein identification with N and C-terminal sequence tags in proteome projects.
AB  - Genome sequences are available for increasing numbers of organisms. The proteomes
      (protein complement expressed by the genome) of many such organisms are being
      studied with two-dimensional (2D) gel electrophoresis. Here we have investigated
      the application of short N-terminal and C-terminal sequence tags to the
      identification of proteins separated on 2D gels. The theoretical N and C termini
      of 15, 519 proteins, representing all SWISS-PROT entries for the organisms
      Mycoplasma genitalium, Bacillus subtilis, Escherichia coli, Saccharomyces
      cerevisiae and human, were analysed. Sequence tags were found to be surprisingly
      specific, with N-terminal tags of four amino acid residues found to be unique for
      between 43% and 83% of proteins, and C-terminal tags of four amino acid residues
      unique for between 74% and 97% of proteins, depending on the species studied.
      Sequence tags of five amino acid residues were found to be even more specific. To
      utilise this specificity of sequence tags for protein identification, we created
      a world-wide web-accessible protein identification program, TagIdent
      (http://www.expasy.ch/www/tools.html), which matches sequence tags of up to six
      amino acid residues as well as estimated protein pI and mass against proteins in
      the SWISS-PROT database. We demonstrate the utility of this identification
      approach with sequence tags generated from 91 different E. coli proteins purified
      by 2D gel electrophoresis. Fifty-one proteins were unambiguously identified by
      virtue of their sequence tags and estimated pI and mass, and a further 11
      proteins identified when sequence tags were combined with protein amino acid
      composition data. We conlcude that the TagIdent identification approach is best
      suited to the identification of proteins from prokaryotes whose complete genome
      sequences are available. The approach is less well suited to proteins from
      eukaryotes, as many eukaryotic proteins are not amenable to sequencing via Edman
      degradation, and tag protein identification cannot be unambiguous unless an
      organism's complete sequence is available.

PMID- 9600842
TI  - Multiple-step method for making exceptionally well-oriented liquid-crystalline
      sols of macromolecular assemblies.
AB  - X-ray fiber diffraction is potentially powerful in solving the atomic structure
      of filamentous assemblies of macromolecules, as demonstrated for tobacco mosaic
      virus. However, it requires extremely well-oriented sols to allow for extraction
      of intensities on closely located layer-lines. A high degree of orientation
      requires a high filament concentration to restrain the orientational freedom, but
      orienting concentrated sols is hampered by their high viscosity. Here, we report
      a systematic method that reproducibly produces extremely good orientation, which
      involves three steps; liquid crystallization, centrifugation and magnetic
      orientation. We found that a slow centrifugation can trigger a dynamic self
      orientation process to form perfectly homogeneous liquid-crystalline sols, and
      further centrifugation to concentrate sols followed by magnetic orientation
      produces exceptionally well-oriented sols. The best-oriented flagellar sol showed
      a disorientation angle of 0.6 degrees as 1sigma of its Gaussian distribution. The
      new method has been successfully applied to many other systems, such as tobacco
      mosaic virus and F-actin.

PMID- 9600843
TI  - Crystal structure of yellow meal worm alpha-amylase at 1.64 A resolution.
AB  - The three-dimensional structure of the alpha-amylase from Tenebrio molitor larvae
      (TMA) has been determined by molecular replacement techniques using diffraction
      data of a crystal of space group P212121 (a=51.24 A; b=93.46 A; c=96.95 A). The
      structure has been refined to a crystallographic R-factor of 17.7% for 58,219
      independent reflections in the 7.0 to 1.64 A resolution range, with root-mean
      square deviations of 0.008 A for bond lengths and 1.482 degrees for bond angles.
      The final model comprises all 471 residues of TMA, 261 water molecules, one
      calcium cation and one chloride anion. The electron density confirms that the N
      terminal glutamine residue has undergone a post-transitional modification
      resulting in a stable 5-oxo-proline residue. The X-ray structure of TMA provides
      the first three-dimensional model of an insect alpha-amylase. The monomeric
      enzyme exhibits an elongated shape approximately 75 Ax46 Ax40 A and consists of
      three distinct domains, in line with models for alpha-amylases from microbial,
      plant and mammalian origin. However, the structure of TMA reflects in the
      substrate and inhibitor binding region a remarkable difference from mammalian
      alpha-amylases: the lack of a highly flexible, glycine-rich loop, which has been
      proposed to be involved in a "trap-release" mechanism of substrate hydrolysis by
      mammalian alpha-amylases. The structural differences between alpha-amylases of
      various origins might explain the specificity of inhibitors directed exclusively
      against insect alpha-amylases.

PMID- 9600844
TI  - Structure of Azotobacter vinelandii 7Fe ferredoxin at 1.35 A resolution and
      determination of the [Fe-S] bonds with 0.01 A accuracy.
AB  - The crystal structure of Azotobacter vinelandii ferredoxin I (FdI) at 100 K has
      been refined at 1.35 A resolution by full matrix block diagonal least-squares
      methods with anisotropic temperature factors for all non-hydrogen atoms and with
      hydrogen atoms included in the model. Fe-S bonds within the [3Fe-4S]+ and [4Fe
      4S]2+ clusters of the protein are determined with an accuracy of at least 0.01 A.
      Analysis of metric parameters reveals greater variation in bonds and angles
      within the [3Fe-4S]+ cluster than in the [4Fe-4S]2+ cluster, whereas the opposite
      is true regarding the cysteine Sgamma atoms ligating to the two [Fe-S] cores. The
      [3Fe-4S]+ core is asymmetrically distorted by the protein matrix but relatively
      uniformly ligated by its three Cys ligands; in contrast the tetrahedral [4Fe
      4S]2+ core is relatively symmetric but non-uniformily ligated by its four Cys
      ligands, three of which occur in a conserved CysxxCysxxCys residue motif.
      Comparison of the [3Fe-4S]+ clusters in FdI and Desulfovibrio gigas ferredoxin
      II, refined at 1.7 A resolution, indicates that within the limit of accuracy of
      the two refinements the cuboidal core is differently distorted in the two
      proteins. Comparison of the [3Fe-4S]+ core in FdI with the structure of a reduced
      [Fe3S4]o synthetic analog indicates that the protein-bound cluster displays
      distortions not intrinsic to the core itself. Nevertheless, both [3Fe-4S]+ and
      [Fe3S4]o cores have metric features consistent with expected trends due to net
      charge on Fe and valency of S, and both exhibit a splayed configuration with
      respect to their three mu2S atoms in the absence of a fourth Fe. Comparison of
      the [4Fe-4S]2+ cluster in FdI with the structures of [Fe4S4]2+ synthetic analogs
      shows that the protein bound and synthetic cubanes are very similar in geometric
      parameters, including the presence of tetragonal distortion in the FdI cluster
      common to this oxidation state.

PMID- 9600845
TI  - Crystal structure of apo-cellular retinoic acid-binding protein type II (R111M)
      suggests a mechanism of ligand entry.
AB  - The crystal structure of unliganded mutant R111M of human cellular retinoic acid
      binding protein type II (apo-CRABPII (R111M)) has been determined at 2.3 A and
      refined to a crystallographic R-factor of 0. 18. Although the mutant protein has
      lower affinity for all-trans-retinoic acid (RA) than the wild-type, it is
      properly folded, and its conformation is very similar to the wild-type. apo
      CRABPII (R111M) crystallizes in space group P1 with two molecules in the unit
      cell. The two molecules have high structural similarity except that their alpha2
      helices differ strikingly. Analyses of the molecular conformation and crystal
      packing environment suggest that one of the two molecules assumes a conformation
      compatible with RA entry. Three structural elements encompassing the opening of
      the binding pocket exhibit large conformational changes, when compared with holo
      CRABPII, which include the alpha2 helix and the betaC-betaD and betaE-betaF
      hairpin loops. The alpha2 helix is unwound at its N terminus, which appears to be
      essential for the opening of the RA-binding pocket. Three arginine side-chains
      (29, 59, and 132) are found with their guanidino groups pointing into the RA
      binding pocket. A three-step mechanism of RA entry has been proposed, addressing
      the opening of the RA entrance, the electrostatic potential that directs entry of
      RA into the binding pocket, and the intramolecular interactions that stabilize
      the RA.CRABPII complex via locking the three flexible structural elements when RA
      is bound.

PMID- 9600846
TI  - Protein folding and protein evolution: common folding nucleus in different
      subfamilies of c-type cytochromes?
AB  - Amino acid sequences of seven subfamilies of cytochromes c (mitochondrial
      cytochromes c, c1; chloroplast cytochromes c6, cf; bacterial cytochromes c2,
      c550, c551; in total 164 sequences) have been compared. Despite extensive
      homology within eukaryotic subfamilies, homology between different subfamilies is
      very weak. Other than the three heme-binding residues (Cys13, Cys14, His18, in
      numeration of horse cytochrome c) there are only four positions which are
      conserved in all subfamilies: Gly/Ala6, Phe/Tyr10, Leu/Val/Phe94 and
      Tyr/Trp/Phe97. In all 17 cytochromes c with known 3D-structures, these residues
      form a network of conserved contacts (6-94, 6-97, 10-94, 10-97 and 94-97).
      Especially strong is the contact between aromatic groups in positions 10 and 97,
      which corresponds to 13 interatomic contacts. As residues 6, 10 and residues 94,
      97 are in (i, i+4) and (i, i+3) positions in the N and C-terminal helices,
      respectively, the above mentioned system of conserved contacts consists mainly of
      contacts between one turn of N-terminal helix and one turn of C-terminal helix.
      The importance of the contacts between interfaces of these helices has been
      confirmed by the existence of these contacts in both equilibrium and kinetic
      molten globule-like folding intermediates, as well as by mutational evidence that
      these contacts are involved in tight packing between the N and C-helices. Since
      these four residues are not involved in heme binding and have no other apparent
      functional role, their conservation in highly diverged cytochromes c suggests
      that they are of a critical importance for protein folding. The author assumes
      that they are involved in a common folding nucleus of all subfamilies of c-type
      cytochromes.

PMID- 9600847
TI  - Backbone and methyl dynamics of the regulatory domain of troponin C: anisotropic
      rotational diffusion and contribution of conformational entropy to calcium
      affinity.
AB  - The N-terminal domain (residues 1 to 90) of chicken skeletal troponin C (NTnC)
      regulates muscle contraction upon the binding of a calcium ion to each of its two
      calcium binding loops. In order to characterize the backbone dynamics of NTnC in
      the apo state (NTnC-apo), we measured and carefully analyzed 15N NMR relaxation
      parameters T1, T2 and NOE at 1H NMR frequencies of 500 and 600 MHz. The overall
      rotational correlation time of NTnC-apo at 29.6 degrees C is 4.86 (+/-0.15) ns.
      The experimental data indicate that the rotational diffusion of NTnC-apo is
      anisotropic with a diffusion anisotropy, D parallel/D perpendicular, of 1.10.
      Additionally, the dynamic properties of side-chains having a methyl group were
      derived from 2H relaxation data of CH2D groups of a partially deuterated sample.
      Based on the dynamic characteristics of TnC, two different levels of "fine
      tuning" of the calcium affinity are presented. Significantly lower backbone order
      parameters (S2), were observed for calcium binding site I relative to site II and
      the contribution of the bond vector fluctuations to the conformational entropy of
      sites I and II was calculated. The conformational entropy loss due to calcium
      binding (DeltaDeltaSp) differs by 1 kcal/mol between sites I and II. This is
      consistent with the different dissociation constants previously measured for
      sites I and II of 16 microM and 1. 7 microM, respectively. In addition to the
      direct role of binding loop dynamics, the side-chain methyl group dynamics play
      an indirect role through the energetics of the calcium-induced structural change
      from a closed to an open state. Our results show that the side-chains which will
      be exposed upon calcium binding have reduced motion in the apo state, suggesting
      that conformational entropic contributions can be used to offset the free energy
      cost of exposing hydrophobic groups. It is clear from this work that a complete
      determination of their dynamic characteristics is necessary in order to fully
      understand how TnC and other proteins are fine tuned to appropriately carry out
      their function.

PMID- 9600848
TI  - Structure-activity relationships and thermal stability of human glutathione
      transferase P1-1 governed by the H-site residue 105.
AB  - Human glutathione transferase P1-1 (GSTP1-1) is polymorphic in amino acid residue
      105, positioned in the substrate binding H-site. To elucidate the role of this
      residue an extensive characterization of GSTP1-1/Ile105 and GSTP1-1/Val105 was
      performed. Mutant enzymes with altered volume and hydrophobicity of residue 105,
      GSTP1-1/Ala105 and GSTP1-1/Trp105, were constructed and included in the study.
      Steady-state kinetic parameters and specific activities were determined using a
      panel of electrophilic substrates, with the aim of covering different types of
      reaction mechanisms. Analysis of the steady-state kinetic parameters indicates
      that the effect of the substitution of the amino acid in position 105 is highly
      dependent on substrate used. When 1-chloro-2,4-dinitrobenzene was used as
      substrate a change in the side-chain of residue 105 seemed primarily to cause
      changes in the KM value, while the kcat value was not distinctively affected.
      With other substrates, such as 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole and
      ethacrynic acid both kcat and KM values were altered by the substitution of amino
      acid 105. The constant for formation of the sigma-complex between 1,3, 5
      trinitrobenzene and glutathione was shown to be dependent upon the volume of the
      amino acid in position 105. The nature of the amino acid in position 105 was also
      shown to affect the thermal stability of the enzyme at 50 degrees C, indicating
      an important role for this residue in the stabilization of the enzyme. The GSTP1
      1/Ile105 variant was approximately two to three times more stable than the Val105
      variant as judged by their half-lives. The presence of glutathione in the
      incubation buffer afforded a threefold increase in the half-lives of the enzymes.
      Thus, the thermal stability of the enzyme and depending on substrate, both KM
      values and turnover numbers are influenced by substitutions in position 105 of
      GSTP1-1.

PMID- 9600849
TI  - Assembly of physalis mottle virus capsid protein in escherichia coli and the role
      of amino acid carboxy termini in the formation of icosahedral particles 

PMID- 9600850
TI  - Announcement 

PMID- 9600851
TI  - The phenylalanyl-tRNA synthetase specifically binds DNA.
AB  - The phenylalanyl-tRNA synthetase (FRS) from Thermus thermophilus is modularly
      composed of several different domains, some of which are not required for
      aminoacylation. In particular, the enzyme has the structural prerequisites for a
      DNA-binding protein. We demonstrate by gel retardation and competition
      experiments that the FRS specifically binds certain DNA sequences of the T.
      thermophilus genomic DNA. Although the implication of this finding is not yet
      understood, increasing evidence indicates an alternative function of this enzyme
      not related to aminoacylation. This might be a fundamental cellular process
      involved in cell proliferation which is related in bacteria and in humans.

PMID- 9600852
TI  - Translational activation by an NtrC enhancer-binding protein.
AB  - The Rhodobacter capsulatus NtrC protein is a bacterial enhancer-binding protein
      that activates the transcription of at least five genes by a mechanism that does
      not require the RpoN RNA polymerase sigma factor. The nifR3-ntrB-ntrC operon in
      R. capsulatus codes for the nitrogen-sensing two component regulators NtrB and
      NtrC, as well as for NifR3, a protein of unknown function that is highly
      conserved in both prokaryotes and eukaryotes. Evidence of a unique translational
      control of NifR3 mediated directly by the NtrC enhancer-binding protein is
      reported. The nifR3-ntrB-ntrC operon is expressed from a single promoter upstream
      of nifR3 with the levels of transcript equivalent in wild-type and ntrC mutants
      under nitrogen-limited or nitrogen-sufficient conditions. LacZ reporter analyses
      of this operon and immunological quantitation of NifR3 and NtrC demonstrate that,
      unlike NtrC levels which remain constant, production of NifR3 is at least ten to
      40-fold reduced in NtrC- strains. NifR3 is increased at least fivefold upon
      nitrogen limitation whereas NtrC production is constitutive. Surprisingly, the
      purified NtrC protein binds cooperatively to the nifR3 promoter region in vitro
      at two sets of tandem binding sites centered at +1 and -81 nucleotides relative
      to the transcriptional start site. Deletion analysis demonstrates that the
      upstream tandem sites are essential for nitrogen and NtrC-dependent production of
      NifR3 in vivo , but are not necessary for nifR3 transcription. These experiments
      indicate that NtrC stimulates the translation of the NifR3 messenger RNA while
      tethered to the promoter DNA. This is in contrast to five other promoters (nifA1,
      nifA2, glnB, mopA and anfA) in R. capsulatus which are transcriptionally
      activated by NtrC bound to one set of tandem binding sites that are centered
      greater than 100 bp upstream of the transcriptional start site.

PMID- 9600853
TI  - Association states of the transcription activator protein NtrC from E. coli
      determined by analytical ultracentrifugation.
AB  - The transcription activator protein NtrC (nitrogen regulatory protein C) can
      catalyze the transition of E. coli RNA polymerase complexed with the sigma54
      factor (RNAP.sigma54) from the closed complex (RNAP.sigma54 bound at the
      promoter) to the open complex (melting of the promoter DNA). This process
      involves phosphorylation of NtrC, assembly of a multimeric NtrC complex at the
      enhancer DNA sequence, interaction of this complex with promoter bound RNAP.
      sigma54 via DNA looping, and hydrolysis of ATP. We have used analytical
      ultracentrifugation to study the different NtrC association states and to derive
      hydrodynamic models for the conformation of the various NtrC species. The
      following results were obtained. (i) The unphosphorylated wild-type protein
      formed a dimer with a measured molecular weight of 102(+/-3) kDa, which compares
      to a calculated molecular weight of 54 kDa for a monomer (concentration range
      studied 2 to 8 microM NtrC monomer). (ii) In the unphosphorylated state one NtrC
      dimer was bound to one binding site as determined with DNA oligonucleotide
      duplexes containing one or two binding sites (concentration range studied 50 to
      1000 nM NtrC dimer). (iii) The data obtained at protein concentrations that were
      below the concentration of binding sites indicate that binding to the DNA duplex
      with two binding sites occurred with essentially no cooperativity. The
      experiments were conducted in the absence of ATP. (iv) The phosphorylated protein
      formed a specific complex at the DNA duplex with the enhancer sequence (two NtrC
      binding sites) that consisted of four dimers (concentration range studied 100 to
      1000 nM NtrC dimer). (v) The formation of this octameric complex was highly
      cooperative, and the data suggest that two DNA strands could bind simultaneously
      to this complex. (vi) From the sedimentation data a model was derived in which
      the NtrC dimer adopts a V shaped structure with the DNA binding domains being
      located at the bottom and the two receiver domains at the top of the V. In this
      conformation higher order NtrC complexes can be stabilized by interaction between
      the phosphorylated receiver domain and the central activation domain of different
      NtrC dimers.

PMID- 9600854
TI  - Simultaneous expression of leukocyte-type 12-lipoxygenase and reticulocyte-type
      15-lipoxygenase in rabbits.
AB  - In rabbit reticulocytes an arachidonic acid 15-lipoxygenase (15-LOX) is expressed
      at high yield. Rescreening a rabbit reticulocyte cDNA library for alternative 15
      LOX transcripts, a full length cDNA which encodes a novel lipoxygenase was
      isolated. The predicted amino acid sequence of this enzyme shared a high degree
      (99%) of identity with the reticulocyte-type 15-lipoxygenase. Among the six amino
      acid residues different in both enzymes a Phe-Leu exchange was detected at
      position 353. Recently, site-directed mutagenesis studies have revealed that this
      amino acid exchange converts a 15-lipoxygenase to a 12-lipoxygenase. In fact,
      when the novel enzyme was expressed in Escherichia coli, mainly 12-lipoxygenation
      of arachidonic acid was observed. The recombinant enzyme exhibited a rather broad
      substrate specificity. Various C-18 and C-20 polyenoic fatty acids and even
      complex substrates such as biomembranes were effectively oxygenated. Thus, the
      novel enzyme may be classified as leukocyte-type 12-lipoxygenase. Genomic
      polymerase chain reaction of the 3' region of the leukocyte-type 12-lipoxygenase
      gene indicated that introns 10 to 13 differed to about 10% from the corresponding
      sequences of the 15-lipoxygenase gene although their size and the intron-exon
      organization were very similar. In the 3'-untranslated region of the novel mRNA a
      C+U-rich, 20-fold repetitive element was found which appears to be highly related
      to the differentiation control element of the 15-lipoxygenase mRNA. Activity
      assays with a variety of cells and tissues prepared from normal rabbits suggested
      that only peripheral monocytes abundantly express the enzyme, suggesting a tissue
      specific regulation of gene expression. These data indicate for the first time
      the co-expression of two separate genes for a reticulocyte-type 15-lipoxygenase
      and for a leukocyte-type 12-lipoxygenase in one species. This is of importance
      for the implication of both enzymes in red blood cell development and
      atherogenesis.

PMID- 9600855
TI  - An intramolecular i-motif: the solution structure and base-pair opening kinetics
      of d(5mCCT3CCT3ACCT3CC).
AB  - We present a high-definition structure of d(5mCCT3CCT3ACCT3CC), a DNA sequence
      which resembles a four-times repeat of the C-rich strand of telomeres and
      centromeres. The structure is monomeric. The CC stretches form four hemi
      protonated C.C base-pairs, belonging to two parallel-stranded duplexes which
      intercalate head-to-tail into an i-motif core. The four grooves of the core are
      similar to those observed previously in i-motif tetramers, with P-P distances
      around 0.9 nm and 1.4 nm for the narrow and wide grooves, respectively. At 0
      degrees C, the structure is formed even at pH 7, despite the required protonation
      of cytidine pairs, suggesting that it may be biologically relevant.The
      intercalation topology of the i-motif core is read off the pattern of inter
      residue cross-peaks along each groove: between H1' protons across the narrow
      grooves, and between amino and H2' protons across the wide grooves. In the hemi
      protonated C.C pairs, the imino proton is shared equally between the two bases,
      as shown by the equal intensities of the NOESY cross-peaks between the imino
      proton and the two cis amino protons of the pair. Short inter-sugar distances and
      the direction of CH1' bonds are consistent with CH1'...O4' hydrogen bonds across
      the narrow grooves, as suggested by Berger et al. (1996). Proc. Natl. Acad. Sci.
      USA, 93, 12116-12121. At one extremity of the i-motif core, the T3A linker loops
      across one of the two wide grooves. It extends the core by stacking of A11, which
      also forms a strongly propeller-twisted reverse-Hoogsteen pair with T8. At the
      other extremity, the two T3 linkers loop side by side across the two narrow
      grooves, extending the core by stacking of a T5.T16 pair which connects the two
      linkers. In this T.T pair between parallel strands, the hydrogen bonds are from
      imino proton to O4, and the base-pair lifetime is 6 ms at 0 degrees C. The
      structures of segments 1 to 7 and 12 to 18, which form the i-motif core and the
      T3 loops, are related by a 2-fold pseudo-symmetry: the geometries and environment
      are so similar that the NOESY spectra are barely resolved. These various
      interactions illustrate how linker sequences may affect the stability,
      intercalation topology and folding pattern of the intramolecular i-motif.

PMID- 9600856
TI  - The three-dimensional structure of shikimate kinase.
AB  - The three-dimensional structure of shikimate kinase from Erwinia chrysanthemi has
      been determined by multiple isomorphous replacement. Two models are presented: a
      high resolution 1.9 A model and a 2.6 A model which contains bound Mg-ADP. The
      enzyme is an alpha/beta protein consisting of a central sheet of five parallel
      beta-strands flanked by alpha-helices with overall topology similar to adenylate
      kinase. Evidence is presented that shikimate kinase undergoes major
      conformational changes on ligand binding. It resembles adenylate kinase in having
      a P-loop containing core structure and two flexible domains which undergo induced
      fit movement on substrate binding. The binding of Mg2+ in the active site of
      shikimate kinase involves direct interaction with two protein side-chains which
      is different from the situation found in adenylate kinase. Shikimate kinase has a
      readily identifiable Walker A-motif and a recognisable but modified Walker B
      motif. Comparison of shikimate kinase to adenylate kinase has led to the
      identification of an adenine-binding motif (I/VDAXQ/NXP). Difference Fourier
      calculations have revealed the shikimate binding site which corresponds to the
      location of the AMP-binding site in adenylate kinase. A model for shikimate
      binding is presented.

PMID- 9600857
TI  - Calorimetric studies of E. coli SSB protein-single-stranded DNA interactions.
      Effects of monovalent salts on binding enthalpy.
AB  - Isothermal titration calorimetry (ITC) was used to examine the effects of
      monovalent salts (NaCl, NaBr, NaF and ChCl) on the binding enthalpy (DeltaHobs)
      for E. coli SSB tetramer binding to the single-stranded oligodeoxythymidylates,
      dT(pT)69 and dT(pT)34 over a wide range of salt concentrations from 10 mM to 2.0
      M (25 degrees C, pH 8.1), and when possible, the binding free energy and entropy
      (DeltaG degrees obs, DeltaS degrees obs). At low monovalent salt concentrations
      (<0.1 M), the total DeltaHobs for saturating all sites on the SSB tetramer with
      ssDNA shows little dependence on salt concentration, but is extremely large and
      exothermic (DeltaHobs=-150(+/-5) kcal/mol). This is much larger than any
      DeltaHobs previously reported for a protein-nucleic acid interaction. However, at
      salt concentrations above 0.1 M, DeltaHobs is quite sensitive to NaCl and NaBr
      concentration, becoming less negative with increasing salt concentration
      (DeltaHobs=-70(+/-1)-kcal/mol in 2 M NaBr). These salt effects on DeltaHobs were
      mainly a function of anion type and concentration, with the largest effects
      observed in NaBr, and then NaCl, with little effect of [NaF]. These large effects
      of salt on DeltaHobs appear to be coupled to a net release of weakly bound anions
      (Br- and Cl-) from the SSB protein upon DNA binding. However, at lower salt
      concentrations (</=0.1 M), specific cation effects on DeltaHobs also are
      observed. Under conditions where we can determine DeltaG degrees obs, DeltaS
      degrees obs, and DeltaHobs (25 degrees C, pH 8.1, 0.17 to 2 M NaBr), SSB binding
      to dT(pT)69 is enthalpically driven with a large unfavorable entropic
      contribution, both of which are dependent upon [NaBr]. These studies show that
      weak anion binding to a protein can result in large effects of salt concentration
      on DeltaHobs (as well as DeltaG degrees obs and DeltaS degrees obs) for a protein
      ssDNA interaction. The possibility of such effects needs to be considered in any
      interpretation of the thermodynamics of this and other protein-nucleic acid
      interactions.

PMID- 9600858
TI  - Electrostatic enhancement of diffusion-controlled protein-protein association:
      comparison of theory and experiment on barnase and barstar.
AB  - The electrostatic enhancement of the association rate of barnase and barstar is
      calculated using a transition-state theory like expression and atomic-detail
      modeling of the protein molecules. This expression predicts that the rate
      enhancement is simply the average Boltzmann factor in the region of
      configurational space where association occurs instantaneously in the diffusion
      controlled limit. Based on experimental evidence, this "transition state" is
      defined by configurations in which, relative to the stereospecifically bound
      complex, the two proteins are shifted apart by approximately 8 A (so a layer of
      water can be accommodated in the interface) and the two binding surfaces are
      rotated away by 0 degrees to 3 degrees. The values of the average Boltzmann
      factor, calculated by solving the Poisson-Boltzmann equation, for the wild-type
      complex and 16 complexes with single mutations are found to correlate well with
      experimental results for the electrostatic rate enhancement. The predicted rate
      enhancement is found to be somewhat insensitive to the precise definition of the
      transition state, due to the long-range nature of electrostatic interactions. The
      experimental ionic strength dependence of the rate enhancement is also reasonably
      reproduced.

PMID- 9600859
TI  - BALB/c and C57Bl/6 mice infected with virulent Burkholderia pseudomallei provide
      contrasting animal models for the acute and chronic forms of human melioidosis.
AB  - Burkholderia pseudomallei is the aetiological agent of melioidosis, a life
      threatening bacterial disease occurring in many species of animals, including
      man. Infection in humans commonly manifests as one of three clinical
      presentations: acute, subacute or chronic disease. Investigations were undertaken
      to assess the suitability of BALB/c and C57Bl/6 mice as animal models for the
      different forms of human melioidosis. The course of infection in BALB/c mice was
      similar to that which occurs in acute human infection. By contrast, infection of
      C57Bl/6 mice appeared to mimic chronic human melioidosis. While BALB/c mice
      suffered a rapidly-progressive bacteraemia which resulted in host death by 96 h,
      C57Bl/6 mice were able to prevent this, and typically remained asymptomatic for
      up to 6 weeks. LD50 values of 4 cells and 2.5 x 10(4) cells for BALB/c and
      C57Bl/6 mice, respectively, reflect these observations. The heightened level of
      resistance to B. pseudomallei observed in C57Bl/6 mice was suggested to have a
      genetic basis, when the susceptibilities of first filial and reciprocal backcross
      generations were examined. Growth kinetics of B. pseudomallei within BALB/c and
      C57Bl/6 peritoneal exudate cell (PEC) cultures were examined to investigate PEC
      microbicidal efficiency as a determinant of host susceptibility. C57Bl/6 PEC
      cultures exhibited greater microbicidal efficiency towards B. pseudomallei when
      compared to BALB/c cells, indicating that susceptibility may be determined by non
      specific, cellular mechanisms. Collectively, these results suggest that the
      BALB/c and C57Bl/6 strains of mice may provide excellent models for acute and
      chronic human melioidosis, respectively.

PMID- 9600860
TI  - Binding characteristics of Escherichia coli enterotoxin b (STb) to the pig
      jejunum and partial characterization of the molecule involved.
AB  - Escherichia coli heat-stable enterotoxin b (STb) causes severe diarrhoea in
      weaning piglets. STb most probably has to bind to intestinal epithelial cells in
      order to achieve its effect. Using biotinylated biologically active STb, we
      developed a semi-quantitative binding assay using indirect fluorescence
      microscopy. We demonstrated the attachment of the biotinylated toxin to
      microvilli of the pig jejunum. However, binding was abolished when biotinylated
      STb was either boiled or treated with 2-mercaptoethanol, treatments known to
      abolish biological activity. Different characteristics of STb attachment to the
      pig small intestine were determined. The reaction was rapid and reached maximum
      intensity after approximately 10 min. The binding was pH dependent showing an
      optimum at pH 5.8. Incubation at either 4 degrees C, 25 degrees C or 37 degrees C
      did not affect the binding. No competition was observed with non-biotinylated
      STb. However, preincubation of biotinylated STb with streptavidin conjugated to
      horseradish peroxidase completely abolished the binding. Pig tissues other than
      jejunum demonstrated binding towards STb including duodenum, ileum, caecum,
      colon, liver, lung, spleen and kidney. The molecule involved was then partially
      characterized. Metaperiodate treatment of the jejunum sections abrogated binding
      but protease treatment had no effect. Enzymatic treatments of jejunal sections
      demonstrated that N- and O-glycosidases, and several exoglycosidases did not
      affect binding, whereas reduced binding was observed with ceramide glycanase and
      alpha-glucosidase, and was completely abolished following neuraminidase
      treatment. Overall, our results suggest that in vitro STb binding was rapid, pH
      dependent, temperature independent, not restricted to jejunum and involves a
      molecule that seems to be composed of a ceramide moiety, terminal neuraminic acid
      and/or alpha-linked terminal glucose residue(s).

PMID- 9600861
TI  - rOmpA is a critical protein for the adhesion of Rickettsia rickettsii to host
      cells.
AB  - rOmpA and rOmpB are immunodominant, surface-exposed proteins of Rickettsia
      rickettsii. Prior evidence suggests that adhesion of R. rickettsii to the host
      cell is mediated by a rickettsial protein. Five monoclonal antibodies to rOmpA,
      five to rOmpB, and one to the rickettsial lipopolysaccharide (LPS) were tested
      for inhibition of rickettsial attachment. All the monoclonal antibodies to rOmpA
      inhibited adhesion of rickettsiae to the L-929 cells with some inhibition rates
      as high as 90%. In contrast, monoclonal antibodies to rOmpB and LPS did not block
      attachment. When Fab fragments of monoclonal antibodies against rOmpA and rOmpB
      were used, similar results were observed as for the intact monoclonals, non
      adhesion and adhesion, respectively. Purified rOmpA showed a competitive
      inhibitive effect on the attachment of R. rickettsii to host cells. Trypsin
      completely digested rOmpA but not rOmpB from the surface of intact R. rickettsii,
      resulting in loss of the ability of the rickettsiae to attach to the host cell.
      rOmpA appears to play an important role in the initial adhesion of R. rickettsii
      to the host cell.

PMID- 9600862
TI  - Monoclonal antibodies to the epitope alpha-Gal-(1-4)-beta-Gal-(1- of Moraxella
      catarrhalis LPS react with a similar epitope in type IV pili of Neisseria
      meningitidis.
AB  - Murine monoclonal antibodies (MAbs) against the A, B and C LPS serotypes of M.
      catarrhalis were generated and their binding specificity was examined in an
      enzyme-linked immunosorbent assay (ELISA). Two broadly cross-reactive monoclonal
      antibodies (MCA1 and MCC2) against the outer core region of LPS were further
      characterized. A panel of synthetic glycoproteins and glycolipids was used to
      determine the binding specificity of the MAbs. MCA1 and MCC2 bound specifically
      to alpha-Gal-(1-4)-beta-Gal of galabiose and globotriose glycoconjugates. The
      reactivity of the MAbs with galabiose was higher than that with globotriose. The
      MAbs could recognize the alpha-Gal-(1-4)-beta-Gal epitope only when it was in a
      terminal position. MCA1 was further shown to react with a similar epitope in the
      glycosylated type IV pili of N. meningitidis, which has been shown to contain a 1
      4 linked digalactose at the terminal part of the saccharide present in the pili.
      MCA1 could efficiently recognize this epitope indicating that it was exposed on
      the surface of the pili.

PMID- 9600863
TI  - Roles of calcium and annexins in phagocytosis and elimination of an attenuated
      strain of Mycobacterium tuberculosis in human neutrophils.
AB  - The phagocytic function of neutrophils is a crucial element in the host defence
      against invading microorganisms. We investigated phagocytosis and intracellular
      killing of an attenuated strain of Mycobacterium tuberculosis(H37Ra) by human
      neutrophils focusing on the role of the cytosolic free calcium concentration
      [Ca2+]i and certain cytosolic calcium-dependent membrane-binding proteins
      annexins. Phagocytic uptake did not trigger a calcium rise and occurred
      independently of different calcium conditions, and in a serum-dependent manner.
      Changes in the viability of H37Ra were determined by agar plate colony count and
      a radiometric assay. Neutrophils showed a capacity to kill ingested mycobacteria
      and this occurred without a rise in [Ca2+]i. The ability to kill H37Ra decreased
      in the absence of extracellular calcium and when intra-extracellular calcium was
      reduced. Immunofluorescence staining revealed that during phagocytosis of H37Ra,
      annexins III, IV and VI translocated from cytoplasm to the proximity of the H37Ra
      containing phagosomes, whereas the localization of annexin I and V remained
      unchanged. The translocation of annexin IV occurred even when Ca2+-depleted
      neutrophils ingested H37Ra in the absence of extracellular calcium. We concluded
      that neutrophil-mediated killing of mycobacteria is a Ca2+-dependent process. The
      fact that the association of certain annexins to the membrane vesicle containing
      H37Ra differ from other phagosomes suggests a selective regulatory mechanism
      during phagocytosis of mycobacteria by neutrophils.

PMID- 9600864
TI  - Endogenous nitric oxide in MDCK-I cells modulates the Vibrio cholerae
      haemagglutinin/protease (HA/P)-mediated cytotoxicity.
AB  - Previously, we have shown that the Vibrio cholerae haemagglutinin/protease (HA/P)
      accounts for significant remaining toxicity of CVD110, an attenuated V. cholerae
      01 El Tor live oral vaccine-strain. The present report demonstrates that
      endogenous nitric oxide (NO) production modulates HA/P-mediated cytotoxicity in
      Madin-Darby canine kidney cell strain I (MDCK-I) epithelial cells. The basal
      levels of endogenous NO suppressed the cytotoxicity of HA/P, whereas inhibition
      of NO production with nitro-L-arginine methyl-ester (L-NAME) made the MDCK-I
      cells susceptible even to low concentrations of the cytotoxin. The inhibition of
      NO production caused a reinforcement of the HA/P- mediated distortion of a tight
      junction-associated protein ZO-1 and increment of filamentous actin at the apical
      and the lateral membrane domains. The mechanism by which NO exerts its modulatory
      action is not likely to be from its direct interaction with the zinc-containing
      catalytic domain of HA/P, since two NO donors, sodium nitroprusside (SNP) and S
      nitroso-N-acetyl-D, L-penicillamine (SNAP), did not affect the proteolytic
      activity of HA/P. In conclusion, the endogenous NO in the MDCK-I cells has a
      modulating effect on the cytotoxicity of HA/P and thus protects the cells against
      the cytotoxin.

PMID- 9600866
TI  - Chemical Index for Volume 149
AB  - Copyright

PMID- 9600867
TI  - Cry1Ac, a bacillus thuringiensis toxin, triggers extracellular Ca2+ influx and
      Ca2+ release from intracellular stores in Cf1 cells
AB  - Intracellular Ca2+ concentration was measured in single Cf1 cells (Choristoneura
      fumiferana, spruce budworm) loaded with Fura-2, a Ca2+-sensitive fluorescent
      probe. Cf1 cells displayed Ca2+ surges in response to Cry1Ac and Cry1C proteins,
      two Cf1-toxic Bacillus thuringiensis products, but not to Cry1Aa and Cry3A, which
      are not toxic to Cf1 cells. In the presence of extracellular Ca2+, the toxin
      induced Ca2+ response was insensitive to methoxyverapamil, a voltage-dependent
      Ca2+ channel blocker, but was abolished by lanthanum, a general inhibitor of Ca2+
      transport. In the absence of external Ca2+, Cry1Ac induced a small intracellular
      Ca2+ transient which was inhibited by TMB-8, a blocker of Ca2+ release from
      inositol-1,4,5-trisphosphate-sensitive pools. Under these conditions,
      thapsigargin, which inhibits intracellular Ca2+-ATPases, elicited a Ca2+ surge
      when applied alone. However, subsequent addition of Cry1Ac failed to induce a
      Ca2+ signal, indicating a depletion of intracellular Ca2+ pools. In Cf1 cells,
      therefore, bioactive B. thuringiensis toxins triggered intracellular Ca2+ surges
      which were mainly due to the influx of extracellular Ca2+ through toxin-made
      pores, as confirmed by planar lipid bilayer experiments. Furthermore, TMB-8- and
      thapsigargin-sensitive Ca2+ stores contributed to the Cry1Ac-induced Ca2+ signal.

PMID- 9600868
TI  - Orientation of snow buntings (Plectrophenax nivalis) close to the magnetic north
      pole
AB  - Orientation experiments were performed with first-year snow buntings
      (Plectrophenax nivalis) during their autumn migration in a natural near-vertical
      geomagnetic field approximately 400 km away from the magnetic north pole.
      Migratory orientation of snow buntings was recorded using two different
      techniques: orientation cage tests and free-flight release experiments.
      Experiments were performed under clear skies, as well as under natural and
      simulated complete overcast. Several experimental manipulations were performed
      including an artificial shift of the E-vector direction of polarized light,
      depolarization of incoming light and a 4 h slow clock-shift experiment. The
      amount of stored fat proved to be decisive for the directional selections of the
      buntings. Fat individuals generally chose southerly mean directions, whereas lean
      birds selected northerly headings. These directional selections seemed to be
      independent of experimental manipulations of the buntings' access to visual cues
      even in the local near-vertical magnetic field. Under clear skies, the buntings
      failed to respond to either a deflection of the E-vector direction of polarized
      light or an experimental depolarization of incoming skylight. When tested under
      natural as well as simulated overcast, the buntings were still able to select a
      meaningful mean direction according to their fat status. Similarly, the free
      flight release test under complete overcast resulted in a well-defined
      southsoutheast direction, possibly influenced by the prevailing light northwest
      wind. Clock-shift experiments did not yield a conclusive result, but the failure
      of these birds to take off during the subsequent free-flight release test may
      indicate some unspecified confusion effect of the treatment.

PMID- 9600869
TI  - Ontogenetic scaling of hydrostatic skeletons: geometric, static stress and
      dynamic stress scaling of the earthworm lumbricus terrestris
AB  - Soft-bodied organisms with hydrostatic skeletons range enormously in body size,
      both during the growth of individuals and in the comparison of species.
      Therefore, body size is an important consideration in an examination of the
      mechanical function of hydrostatic skeletons. The scaling of hydrostatic
      skeletons cannot be inferred from existing studies of the lever-like skeletons of
      vertebrates and arthropods because the two skeleton types function by different
      mechanisms. Hydrostats are constructed of an extensible body wall in tension
      surrounding a fluid or deformable tissue under compression. It is the pressurized
      internal fluid (rather than the rigid levers of vertebrates and arthropods) that
      enables the maintenance of posture, antagonism of muscles and transfer of muscle
      forces to the environment. The objectives of the present study were (1) to define
      the geometric, static stress and dynamic stress similarity scaling hypotheses for
      hydrostatic skeletons on the basis of their generalized form and function, and
      (2) to apply these similarity hypotheses in a study of the ontogenetic scaling of
      earthworms, Lumbricus terrestris, to determine which parameters of skeletal
      function are conserved or changed as a function of body mass during growth (from
      0.01 to 8 g). Morphometric measurements on anesthetized earthworms revealed that
      the earthworms grew isometrically; the external proportions and number of
      segments were constant as a function of body size. Calculations of static
      stresses (forces per cross-sectional area in the body wall) during rest and
      dynamic stresses during peristaltic crawling (calculated from measurements of
      internal pressure and body wall geometry) revealed that the earthworms also
      maintained static and dynamic stress similarity, despite a slight increase in
      body wall thickness in segment 50 (but not in segment 15). In summary, the
      hydrostatic skeletons of earthworms differ fundamentally from the rigid, lever
      like skeletons of their terrestrial counterparts in their ability to grow
      isometrically while maintaining similarity in both static and dynamic stresses.

PMID- 9600870
TI  - Innervation pattern of a pool of nine excitatory motor neurons in the flexor
      tibiae muscle of a locust hind leg
AB  - The flexor tibiae muscle of a locust hind leg consists of 10-11 pairs of fibre
      bundles in the main body of the muscle and a distal pair of bundles that form the
      accessory flexor muscle, all of which insert onto a common tendon. It is much
      smaller than the antagonistic extensor tibiae muscle and yet it is innervated by
      nine excitatory motor neurons, compared with only two for the extensor. To
      determine the pattern of innervation within the muscle by individual motor
      neurons, branches of the nerve (N5B2) that supplies the different muscle bundles
      were backfilled to reveal somata in the metathoracic ganglion. This showed that
      different muscle bundles are innervated by different numbers of excitatory motor
      neurons. Physiological mapping of the innervation was then carried out by
      intracellular recordings from the somata of flexor motor neurons in the
      metathoracic ganglion using microelectrodes. Spikes were evoked in these neurons
      by the injection of current, and matching junctional potentials were sought in
      fibres throughout the muscle using a second intracellular electrode. Each motor
      neuron innervates only a restricted array of muscle fibres and, although some
      innervate a larger array than others, none innervates fibres throughout the
      muscle. Some motor neurons innervate only proximal fibres and others only more
      distal fibres, so that the most proximal and most distal bundles of muscle fibres
      are innervated by non-overlapping sets of motor neurons. More motor neurons
      innervate proximal bundles than distal ones, and there are some asymmetries in
      the number of motor neurons innervating corresponding bundles on either side of
      the tendon. Individual motor neurons cause slow, fast or intermediate movements
      of the tibia, but their patterns of innervation overlap in the different muscle
      bundles. Furthermore, individual muscle fibres may also be innervated by motor
      neurons with different properties.

PMID- 9600871
TI  - Long-lasting depolarization of leech neurons mediated by receptors with a
      nicotinic binding site
AB  - The serotonergic Retzius neurons of the leech midbody ganglia respond in a
      complex manner to pressure pulses of acetylcholine (ACh) applied onto their soma
      with a fast depolarization followed by a slower hyperpolarization and an
      additional delayed long-lasting depolarization. The delayed depolarization is the
      subject of the present study. The delayed depolarization could be elicited by
      long (>1 s) ACh pressure pulses or by short pulses (10 ms) of carbachol, nicotine
      and DMPP, but not by muscarinic agonists. It was inhibited by bath application of
      nicotine (10-100 micromol l-1), strychnine (100 micromol l-1) and atropine (10
      100 micromol l-1). Nicotinic antagonists that blocked the fast depolarization and
      the slow hyperpolarization (100 micromol l-1 mecamylamine and d-tubocurarine) did
      not affect the delayed depolarization induced by carbachol. Partial replacement
      of the extracellular Na+ by glucamine caused a decrease in the amplitude of the
      response and a shift of its reversal potential to more negative values. Carbachol
      pulses applied to Retzius neurons of the ganglia innervating the reproductive
      segments elicited delayed depolarizations of much smaller amplitude than the ones
      recorded in Retzius neurons from standard segments. The delayed depolarization
      could be elicited by the application of short agonist pulses onto different loci
      over the surface of the ganglion, at a distance from the soma. Isolated cultured
      Retzius neurons did not exhibit the delayed depolarization although they readily
      expressed the earlier phases of the complex cholinergic response. Carbachol
      pulses applied to the soma of other neurons in the leech ganglion produced a
      variety of specific responses.The results suggest that the delayed depolarization
      was produced by the activation of a cationic conductance mediated by receptors
      with a pharmacological profile similar to that of the <IMG
      src="/images/symbols/&agr ;.gif" WIDTH="9" HEIGHT= "12" ALIGN="BOTTOM"
      NATURALSIZEFLAG="3">9 nicotinic receptors and was not a byproduct of the early
      phases of the cholinergic response. The response seemed to be initiated in the
      extensive neuropilar processes of the Retzius cell, enabling a persistent
      excitatory signal.

PMID- 9600872
TI  - Basal acetylcholine release in leech ganglia depolarizes neurons through
      receptors with a nicotinic binding site
AB  - The response of Retzius neurons, the main neuronal source of serotonin in the
      leech nervous system, to cholinergic agonists has been extensively investigated.
      In this study, we analyzed the effects of inhibiting the acetylcholinesterase
      (AChE) activity in the leech midbody ganglion on the electrophysiological
      activity of the Retzius neurons. Bath application of neostigmine and
      physostigmine (0.1-100 &mgr;mol l-1) produced, after a delay, a strong
      depolarization of the Retzius neurons with a dose-dependent amplitude and
      latency. The amplitude of this depolarization increased as the extracellular
      level of Ca2+ increased and decreased as the extracellular level of Ca2+
      decreased. The response to neostigmine and physostigmine was inhibited by curare
      (100 &mgr;mol l-1), nicotine (10 &mgr;mol l-1), atropine (100 &mgr;mol l-1) and
      strychnine (100 &mgr;mol l-1), but was not affected by mecamylamine (100 &mgr;mol
      l-1) or hexamethonium (100 &mgr;mol l-1). Superfusion with solutions containing
      100 &mgr;mol l-1 strychnine or atropine produced a progressive hyperpolarization
      of the Retzius neurons, while superfusion with 100 &mgr;mol l-1 curare did not.
      The hyperpolarization induced by atropine was inhibited in the presence of
      curare. Other neurons in the ganglion showed distinctive responses to the AChE
      inhibitors that were coincident with their responses to cholinergic agonists. The
      results suggest the existence of a basal level of acetylcholine (ACh) release in
      the leech ganglion that is powerfully counteracted by endogenous AChE activity.
      Under control conditions, this basal release appears to be sufficient to generate
      an ACh tonus that regulates the membrane potential of Retzius neurons. Since
      these neurons can support a sustained firing rate, which is dependent on the
      membrane potential, the results presented in this report suggest that the basal
      ACh tonus regulates the output of these neuromodulatory serotonergic neurons.

PMID- 9600873
TI  - Swimming kinematics and respiratory behaviour of xenopus laevis larvae raised in
      altered gravity
AB  - We examined the respiratory behaviours and swimming kinematics of Xenopus laevis
      tadpoles hatched in microgravity (Space Shuttle), simulated microgravity
      (clinostat) and hypergravity (3 g centrifuge). All observations were made in the
      normal 1 g environment. Previous research has shown that X. laevis raised in
      microgravity exhibit abnormalities in their lungs and vestibular system upon
      return to 1 g. The tadpoles raised in true microgravity exhibited a significantly
      lower tailbeat frequency than onboard 1 g centrifuge controls on the day of
      landing (day0), but this behaviour normalized within 9 days. The two groups did
      not differ significantly in buccal pumping rates. Altered buoyancy in the space
      flight microgravity tadpoles was indicated by an increased swimming angle on the
      day after landing (day1). Tadpoles raised in simulated microgravity differed to a
      greater extent in swimming behaviours from their 1 g controls. The tadpoles
      raised in hypergravity showed no substantive effects on the development of
      swimming or respiratory behaviours, except swimming angle. Together, these
      results show that microgravity has a transient effect on the development of
      locomotion in X. laevis tadpoles, most notably on swimming angle, indicative of
      stunted lung development. On the basis of the behaviours we studied, there is no
      indication of neuromuscular retardation in amphibians associated with
      embryogenesis in microgravity.

PMID- 9600874
TI  - Regulation of ion transport across lamprey (Lampetra fluviatilis) erythrocyte
      membrane by oxygen tension
AB  - We have measured the effects of oxygen tension on the transport of Na+, K+ and Cl
      across the erythrocyte membrane of the lamprey Lampetra fluviatilis. The
      transport of each ion was affected by the oxygen tension of the medium. Hypoxic
      conditions (PO2 2 kPa) caused an increase in the acidification-induced influx of
      Na+ via Na+/H+ exchange. The influx of K+ was only slightly affected by the
      oxygenation of the medium. In contrast, the basal K+ efflux, measured using the
      radioactive isotope 43K, was markedly reduced by decreasing the oxygen tension of
      the medium, whereas the K+ flux in hypotonic medium was not affected. Only minor
      effects of hypoxic conditions on the influx of Cl- were observed in either
      isotonic or hypotonic conditions (there was a tendency for the isotonic influx to
      increase) or on the efflux in isotonic conditions. However, deoxygenation caused
      a marked reduction in the Cl- efflux in hypotonic conditions. The results show
      that oxygen tension has a marked effect on the pH and volume regulatory transport
      pathways of lamprey erythrocytes. For K+ and Cl-, the regulation appears to be
      asymmetric, i.e. influx and efflux are affected differently.

PMID- 9600875
TI  - Hypertrehalosaemic neuropeptides decrease levels of the glycolytic signal
      fructose 2,6-bisphosphate in cockroach fat body
AB  - In cockroach fat body, trehalogenesis and glycolysis compete for glucose
      phosphates as common substrates. During trehalogenesis, glycolysis is inhibited,
      although the mechanism responsible for this is not known. Incubation of the
      isolated fat body from the Argentine cockroach Blaptica dubia with an extract of
      the corpora cardiaca containing as little as 0.005 gland equivalents ml-1 of
      incubation medium increased the release of trehalose (anthrone-positive material)
      from the tissue by more than 100 %. The content of the glycolytic activator
      fructose 2,6-bisphosphate was decreased by up to 50 %. A decapeptide was isolated
      from the corpora cardiaca of B. dubia and shown to be identical to the naturally
      occurring Blaberus discoidalis hypertrehalosaemic peptide (Bld HrTH), which was
      also found in the corpora cardiaca. Synthetic Bld HrTH at 2 nmol l-1 and above
      increased trehalose production and decreased the content of fructose 2,6
      bisphosphate to the same extent as did corpus cardiacum extract. The octapeptides
      Periplaneta americana cardioacceleratory hormones I and II (Pea CAH-I and Pea CAH
      II) also had a significant effect on both parameters. Fructose 2,6-bisphosphate
      is a potent activator of phosphofructokinase from cockroach fat body if the
      enzyme is assayed at near-physiological concentrations of substrates and
      effectors. It is suggested that, because of the decrease in fructose 2,6
      bisphosphate levels in the fat body, the activity of the key glycolytic enzyme
      phosphofructokinase is diminished. This can explain the inhibition of glycolytic
      flux by hypertrehalosaemic peptides which alters the balance of glucose
      metabolism in favour of trehalose formation.

PMID- 9600876
TI  - An analysis of the relationship between the response characteristics and
      topography of directional- and non-directional auditory neurons in the torus
      semicircularis of the rainbow trout
AB  - The response characteristics of auditory neurons in the multimodal midbrain torus
      semicircularis of rainbow trout were analyzed to examine their topography and
      functional differences. This analysis included the localization of recording
      sites, the measurement of spontaneous activity, the ratio of transient/sustained
      activity, and the synchronization, latency, preferred direction and directional
      range of the response. On average, units with a directionally selective (DS)
      response are positioned 60 microm more dorsally than other auditory units.
      Directionally selective units usually have a higher response rate, a higher
      transient/sustained activity ratio and are better synchronized. Auditory units
      encountered within the same electrode track tend to be either all DS or all non
      DS. Within a track, there is no uniformity of the response characteristics
      observed except that the preferred direction of DS units appears to be the same.
      The anatomical stratification of the torus, containing 66 000 somata (5-10 microm
      in diameter), does not match the electrophysiologically observed vertical
      distribution of functionally distinct units. On the basis of the topographical
      distribution of response characteristics, two types of well-synchronized DS units
      can be distinguished, hypothetically representing separate channels for the
      processing of acoustic motion and (mainly) pressure information. A third type of
      DS unit which receives input from both these channels and actually encodes the
      source direction uniquely for all directions is postulated.

PMID- 9600877
TI  - Neural modulation of salt secretion in teleostopercular epithelium by 2
      adrenergic receptors and inositol 1,4,5-trisphosphate
AB  - Opercular epithelia from seawater-adapted killifish (Fundulus heteroclitus) were
      dissected with the nerve intact, mounted in Ussing-style membrane chambers and
      bathed in symmetrical saline solutions. Nerve stimulation rapidly inhibited
      transepithelial current (a measure of Cl- secretion rate) by 27.3+/-3.3 % (N=22),
      and the effect could be sustained for more than 10 min using intermittent pulse
      trains at 10 Hz. The effect was blocked in a dose-dependent manner by yohimbine,
      but not by propranolol, atropine or tubocurarine, indicating mediation by <IMG
      src="/images/symbols/&agr ;.gif" WIDTH= "9" HEIGHT="12" ALIGN="BOTTOM"
      NATURALSIZEFLAG="3">2-adrenergic receptors. The effect was also present, but
      significantly diminished, in opercular membranes from animals that had been
      transferred to sea water for 48 h (18+/-8.6 % inhibition, N=14). The resting
      current and the effect were absent in membranes from freshwater-adapted animals.
      The addition of clonidine (1.0 micromol l-1 serosal side) started to inhibit Cl-
      current after 40-60 s; immediately before this, at 30 s, there was a significant
      rise (P<0.05, N=14) in tissue inositol 1,4,5, -trisphosphate (InsP3) level, but
      no change at later times, compared with LiCl-treated control membranes and
      measured by radiolabeled receptor assay. The results indicate that seawater
      adapted killifish can decrease their Cl- secretion rate through the action of the
      sympathetic nervous system, a response appropriate for the entry of estuarine
      fish to fresh water, and that the effect is mediated by <IMG
      src="/images/symbols/&agr ;.gif" WIDTH="9" HEIGHT="12" ALIGN="BOTTOM"
      NATURALSIZEFLAG="3">2-adrenoceptors via InsP3. The results imply that euryhaline
      fish entering fresh water can undergo an autonomic reflex reduction in salt
      secretion that does not require a stress response.

PMID- 9600878
TI  - Hearing in mole crickets (Orthoptera: gryllotalpidae) at sonic and ultrasonic
      frequencies
AB  - We have studied auditory responses in two species of mole cricket (Scapteriscus
      borellii and S. abbreviatus) to determine (1) whether they show sensitivity to
      ultrasound, (2) whether their hearing (at both low and high frequencies) is based
      on the same neural circuitry as that of true crickets, and (3) whether ultrasound
      sensitivity in different mole cricket species varies with their ability to fly.
      S. borellii are sensitive to ultrasonic frequencies. There is evidence of a
      segregation of frequency bands in prothoracic auditory neurons. There are two
      pairs of &ohgr ; neurons (ONs) with similar morphology to ON1 of true crickets.
      The two pairs of ONs differ in tuning. One pair has two sensitivity peaks: at the
      frequency of the calling song of this species (3 kHz), and in the ultrasonic
      range (25 kHz). The other pair lacks the high-frequency sensitivity and responds
      exclusively to frequencies in the range of the species song. These two types are
      not morphologically distinguishable. In S. abbreviatus, only one class of ON was
      found. S. abbreviatus ONs are narrowly tuned to the frequency of the species'
      calls. A T-neuron had the best ultrasonic frequency sensitivity in S. borellii.
      This cell showed a broad tuning to ultrasonic frequencies and was inhibited by
      low-frequency stimuli. A morphologically similar neuron was also recorded in S.
      abbreviatus, but lacked the high-frequency sensitivity peak of that in S.
      borellii. We also assessed the responses of flying S. borellii to ultrasound
      using field playbacks to free-flying animals. The attractiveness of broadcast
      calling song was diminished by the addition of an ultrasound signal, indicating
      that S. borellii avoid high-frequency sound. The results indicate that mole
      crickets process low-frequency auditory stimuli using mechanisms similar to those
      of true crickets. They show a negative behavioural response to high-frequency
      stimuli, as do true crickets, but the organization of ultrasound-sensitive
      auditory circuitry in mole crickets differs from that of true crickets.

PMID- 9600879
TI  - The keratinocyte growth-differentiation switch.
AB  - Growth/differentiation control of normal epithelial cells has been relatively
      understudied, because of the complexities involved in their cultivation and
      characterization. The present review is focused on progress in this area using
      the mouse primary keratinocyte system. This system reproduces under well defined
      culture conditions the switch between epithelial cell growth and differentiation
      which occurs in vivo, and enables the study of cells derived from wild type mice
      as well as mice with specific genetic alterations.

PMID- 9600880
TI  - A new approach to fighting cancer?

PMID- 9600881
TI  - Nucleic acid enzymes: playing with a fuller deck.

PMID- 9600882
TI  - Computational biomolecular science.

PMID- 9600883
TI  - Measuring genome evolution.
AB  - The determination of complete genome sequences provides us with an opportunity to
      describe and analyze evolution at the comprehensive level of genomes. Here we
      compare nine genomes with respect to their protein coding genes at two levels:
      (i) we compare genomes as "bags of genes" and measure the fraction of orthologs
      shared between genomes and (ii) we quantify correlations between genes with
      respect to their relative positions in genomes. Distances between the genomes are
      related to their divergence times, measured as the number of amino acid
      substitutions per site in a set of 34 orthologous genes that are shared among all
      the genomes compared. We establish a hierarchy of rates at which genomes have
      changed during evolution. Protein sequence identity is the most conserved,
      followed by the complement of genes within the genome. Next is the degree of
      conservation of the order of genes, whereas gene regulation appears to evolve at
      the highest rate. Finally, we show that some genomes are more highly organized
      than others: they show a higher degree of the clustering of genes that have
      orthologs in other genomes.

PMID- 9600884
TI  - SMART, a simple modular architecture research tool: identification of signaling
      domains.
AB  - Accurate multiple alignments of 86 domains that occur in signaling proteins have
      been constructed and used to provide a Web-based tool (SMART: simple modular
      architecture research tool) that allows rapid identification and annotation of
      signaling domain sequences. The majority of signaling proteins are multidomain in
      character with a considerable variety of domain combinations known. Comparison
      with established databases showed that 25% of our domain set could not be deduced
      from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine
      the modular architectures of single sequences or genomes; application to the
      entire yeast genome revealed that at least 6.7% of its genes contain one or more
      signaling domains, approximately 350 greater than previously annotated. The
      process of constructing SMART predicted (i) novel domain homologues in unexpected
      locations such as band 4.1-homologous domains in focal adhesion kinases; (ii)
      previously unknown domain families, including a citron-homology domain; (iii)
      putative functions of domain families after identification of additional family
      members, for example, a ubiquitin-binding role for ubiquitin-associated domains
      (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin
      receptors further implicating these molecules in axonal guidance; (v) signaling
      domains in known disease genes such as SPRY domains in both marenostrin/pyrin and
      Midline 1; (vi) domains in unexpected phylogenetic contexts such as
      diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein
      misclassifications exemplified by a predicted pleckstrin homology domain in a
      Candida albicans protein, previously described as an integrin.

PMID- 9600885
TI  - Highly specific protein sequence motifs for genome analysis.
AB  - We present a method for discovering conserved sequence motifs from families of
      aligned protein sequences. The method has been implemented as a computer program
      called EMOTIF (http://motif. stanford.edu/emotif). Given an aligned set of
      protein sequences, EMOTIF generates a set of motifs with a wide range of
      specificities and sensitivities. EMOTIF also can generate motifs that describe
      possible subfamilies of a protein superfamily. A disjunction of such motifs often
      can represent the entire superfamily with high specificity and sensitivity. We
      have used EMOTIF to generate sets of motifs from all 7,000 protein alignments in
      the BLOCKS and PRINTS databases. The resulting database, called IDENTIFY
      (http://motif. stanford.edu/identify), contains more than 50,000 motifs. For each
      alignment, the database contains several motifs having a probability of matching
      a false positive that range from 10(-10) to 10(-5). Highly specific motifs are
      well suited for searching entire proteomes, while generating very few false
      predictions. IDENTIFY assigns biological functions to 25-30% of all proteins
      encoded by the Saccharomyces cerevisiae genome and by several bacterial genomes.
      In particular, IDENTIFY assigned functions to 172 of proteins of unknown function
      in the yeast genome.

PMID- 9600886
TI  - A statistical mechanical model for beta-hairpin kinetics.
AB  - Understanding the mechanism of protein secondary structure formation is an
      essential part of the protein-folding puzzle. Here, we describe a simple
      statistical mechanical model for the formation of a beta-hairpin, the minimal
      structural element of the antiparallel beta-pleated sheet. The model accurately
      describes the thermodynamic and kinetic behavior of a 16-residue, beta-hairpin
      forming peptide, successfully explaining its two-state behavior and apparent
      negative activation energy for folding. The model classifies structures according
      to their backbone conformation, defined by 15 pairs of dihedral angles, and is
      further simplified by considering only the 120 structures with contiguous
      stretches of native pairs of backbone dihedral angles. This single sequence
      approximation is tested by comparison with a more complete model that includes
      the 2(15) possible conformations and 15 x 2(15) possible kinetic transitions.
      Finally, we use the model to predict the equilibrium unfolding curves and
      kinetics for several variants of the beta-hairpin peptide.

PMID- 9600887
TI  - Coupling the folding of homologous proteins.
AB  - The empirical observation that homologous proteins fold to similar structures is
      used to enhance the capabilities of an ab initio algorithm to predict protein
      conformations. A penalty function that forces homologous proteins to look alike
      is added to the potential and is employed in the coupled energy optimization of
      several homologous proteins. Significant improvement in the quality of the
      computed structures (as compared with the computational folding of a single
      protein) is demonstrated and discussed.

PMID- 9600888
TI  - Photoactive yellow protein: a structural prototype for the three-dimensional fold
      of the PAS domain superfamily.
AB  - PAS domains are found in diverse proteins throughout all three kingdoms of life,
      where they apparently function in sensing and signal transduction. Although a
      wealth of useful sequence and functional information has become recently
      available, these data have not been integrated into a three-dimensional (3D)
      framework. The very early evolutionary development and diverse functions of PAS
      domains have made sequence analysis and modeling of this protein superfamily
      challenging. Limited sequence similarities between the approximately 50-residue
      PAS repeats and one region of the bacterial blue-light photosensor photoactive
      yellow protein (PYP), for which ground-state and light-activated crystallographic
      structures have been determined to high resolution, originally were identified in
      sequence searches using consensus sequence probes from PAS-containing proteins.
      Here, we found that by changing a few residues particular to PYP function, the
      modified PYP sequence probe also could select PAS protein sequences. By mapping a
      typical approximately 150-residue PAS domain sequence onto the entire
      crystallographic structure of PYP, we show that the PAS sequence similarities and
      differences are consistent with a shared 3D fold (the PAS/PYP module) with
      obvious potential for a ligand-binding cavity. Thus, PYP appears to
      prototypically exhibit all the major structural and functional features
      characteristic of the PAS domain superfamily: the shared PAS/PYP modular domain
      fold of approximately 125-150 residues, a sensor function often linked to ligand
      or cofactor (chromophore) binding, and signal transduction capability governed by
      heterodimeric assembly (to the downstream partner of PYP). This 3D PAS/PYP module
      provides a structural model to guide experimental testing of hypotheses regarding
      ligand-binding, dimerization, and signal transduction.

PMID- 9600889
TI  - New methods of structure refinement for macromolecular structure determination by
      NMR.
AB  - Recent advances in multidimensional NMR methodology have permitted solution
      structures of proteins in excess of 250 residues to be solved. In this paper, we
      discuss several methods of structure refinement that promise to increase the
      accuracy of macromolecular structures determined by NMR. These methods include
      the use of a conformational database potential and direct refinement against
      three-bond coupling constants, secondary 13C shifts, 1H shifts, T1/T2 ratios, and
      residual dipolar couplings. The latter two measurements provide long range
      restraints that are not accessible by other solution NMR parameters.

PMID- 9600891
TI  - Precise sequence complementarity between yeast chromosome ends and two classes of
      just-subtelomeric sequences.
AB  - The terminal regions (last 20 kb) of Saccharomyces cerevisiae chromosomes
      universally contain blocks of precise sequence similarity to other chromosome
      terminal regions. The left and right terminal regions are distinct in the sense
      that the sequence similarities between them are reverse complements. Direct
      sequence similarity occurs between the left terminal regions and also between the
      right terminal regions, but not between any left ends and right ends. With minor
      exceptions the relationships range from 80% to 100% match within blocks. The
      regions of similarity are composites of familiar and unfamiliar repeated
      sequences as well as what could be considered "single-copy" (or better "two
      copy") sequences. All terminal regions were compared with all other chromosomes,
      forward and reverse complement, and 768 comparisons are diagrammed. It appears
      there has been an extensive history of sequence exchange or copying between
      terminal regions. The subtelomeric sequences fall into two classes. Seventeen of
      the chromosome ends terminate with the Y' repeat, while 15 end with the 800-nt
      "X2" repeats just adjacent to the telomerase simple repeats. The just-subterminal
      repeats are very similar to each other except that chromosome 1 right end is more
      divergent.

PMID- 9600890
TI  - Estimation of evolutionary distances under stationary and nonstationary models of
      nucleotide substitution.
AB  - Estimation of evolutionary distances has always been a major issue in the study
      of molecular evolution because evolutionary distances are required for estimating
      the rate of evolution in a gene, the divergence dates between genes or organisms,
      and the relationships among genes or organisms. Other closely related issues are
      the estimation of the pattern of nucleotide substitution, the estimation of the
      degree of rate variation among sites in a DNA sequence, and statistical testing
      of the molecular clock hypothesis. Mathematical treatments of these problems are
      considerably simplified by the assumption of a stationary process in which the
      nucleotide compositions of the sequences under study have remained approximately
      constant over time, and there now exist fairly extensive studies of stationary
      models of nucleotide substitution, although some problems remain to be solved.
      Nonstationary models are much more complex, but significant progress has been
      recently made by the development of the paralinear and LogDet distances. This
      paper reviews recent studies on the above issues and reports results on
      correcting the estimation bias of evolutionary distances, the estimation of the
      pattern of nucleotide substitution, and the estimation of rate variation among
      the sites in a sequence.

PMID- 9600892
TI  - A unified statistical framework for sequence comparison and structure comparison.
AB  - We present an approach for assessing the significance of sequence and structure
      comparisons by using nearly identical statistical formalisms for both sequence
      and structure. Doing so involves an all-vs.-all comparison of protein domains
      [taken here from the Structural Classification of Proteins (scop) database] and
      then fitting a simple distribution function to the observed scores. By using this
      distribution, we can attach a statistical significance to each comparison score
      in the form of a P value, the probability that a better score would occur by
      chance. As expected, we find that the scores for sequence matching follow an
      extreme-value distribution. The agreement, moreover, between the P values that we
      derive from this distribution and those reported by standard programs (e.g.,
      BLAST and FASTA validates our approach. Structure comparison scores also follow
      an extreme-value distribution when the statistics are expressed in terms of a
      structural alignment score (essentially the sum of reciprocated distances between
      aligned atoms minus gap penalties). We find that the traditional metric of
      structural similarity, the rms deviation in atom positions after fitting aligned
      atoms, follows a different distribution of scores and does not perform as well as
      the structural alignment score. Comparison of the sequence and structure
      statistics for pairs of proteins known to be related distantly shows that
      structural comparison is able to detect approximately twice as many distant
      relationships as sequence comparison at the same error rate. The comparison also
      indicates that there are very few pairs with significant similarity in terms of
      sequence but not structure whereas many pairs have significant similarity in
      terms of structure but not sequence.

PMID- 9600893
TI  - Folding funnels and frustration in off-lattice minimalist protein landscapes.
AB  - A full quantitative understanding of the protein folding problem is now becoming
      possible with the help of the energy landscape theory and the protein folding
      funnel concept. Good folding sequences have a landscape that resembles a rough
      funnel where the energy bias towards the native state is larger than its
      ruggedness. Such a landscape leads not only to fast folding and stable native
      conformations but, more importantly, to sequences that are robust to variations
      in the protein environment and to sequence mutations. In this paper, an off
      lattice model of sequences that fold into a beta-barrel native structure is used
      to describe a framework that can quantitatively distinguish good and bad folders.
      The two sequences analyzed have the same native structure, but one of them is
      minimally frustrated whereas the other one exhibits a high degree of frustration.

PMID- 9600894
TI  - Optimizing the stability of single-chain proteins by linker length and
      composition mutagenesis.
AB  - Linker length and composition were varied in libraries of single-chain Arc
      repressor, resulting in proteins with effective concentrations ranging over six
      orders of magnitude (10 microM-10 M). Linkers of 11 residues or more were
      required for biological activity. Equilibrium stability varied substantially with
      linker length, reaching a maximum for glycine-rich linkers containing 19
      residues. The effects of linker length on equilibrium stability arise from
      significant and sometimes opposing changes in folding and unfolding kinetics. By
      fixing the linker length at 19 residues and varying the ratio of Ala/Gly or
      Ser/Gly in a 16-residue-randomized region, the effects of linker flexibility were
      examined. In these libraries, composition rather than sequence appears to
      determine stability. Maximum stability in the Ala/Gly library was observed for a
      protein containing 11 alanines and five glycines in the randomized region of the
      linker. In the Ser/Gly library, the most stable protein had seven serines and
      nine glycines in this region. Analysis of folding and unfolding rates suggests
      that alanine acts largely by accelerating folding, whereas serine acts
      predominantly to slow unfolding. These results demonstrate an important role for
      linker design in determining the stability and folding kinetics of single-chain
      proteins and suggest strategies for optimizing these parameters.

PMID- 9600895
TI  - Architecture and mechanism of the light-harvesting apparatus of purple bacteria.
AB  - Photosynthetic organisms fuel their metabolism with light energy and have
      developed for this purpose an efficient apparatus for harvesting sunlight. The
      atomic structure of the apparatus, as it evolved in purple bacteria, has been
      constructed through a combination of x-ray crystallography, electron microscopy,
      and modeling. The detailed structure and overall architecture reveals a
      hierarchical aggregate of pigments that utilizes, as shown through femtosecond
      spectroscopy and quantum physics, elegant and efficient mechanisms for primary
      light absorption and transfer of electronic excitation toward the photosynthetic
      reaction center.

PMID- 9600896
TI  - Electrostatic steering and ionic tethering in enzyme-ligand binding: insights
      from simulations.
AB  - To bind at an enzyme's active site, a ligand must diffuse or be transported to
      the enzyme's surface, and, if the binding site is buried, the ligand must diffuse
      through the protein to reach it. Although the driving force for ligand binding is
      often ascribed to the hydrophobic effect, electrostatic interactions also
      influence the binding process of both charged and nonpolar ligands. First,
      electrostatic steering of charged substrates into enzyme active sites is
      discussed. This is of particular relevance for diffusion-influenced enzymes. By
      comparing the results of Brownian dynamics simulations and electrostatic
      potential similarity analysis for triose-phosphate isomerases, superoxide
      dismutases, and beta-lactamases from different species, we identify the conserved
      features responsible for the electrostatic substrate-steering fields. The
      conserved potentials are localized at the active sites and are the primary
      determinants of the bimolecular association rates. Then we focus on a more subtle
      effect, which we will refer to as "ionic tethering." We explore, by means of
      molecular and Brownian dynamics simulations and electrostatic continuum
      calculations, how salt links can act as tethers between structural elements of an
      enzyme that undergo conformational change upon substrate binding, and thereby
      regulate or modulate substrate binding. This is illustrated for the lipase and
      cytochrome P450 enzymes. Ionic tethering can provide a control mechanism for
      substrate binding that is sensitive to the electrostatic properties of the
      enzyme's surroundings even when the substrate is nonpolar.

PMID- 9600898
TI  - A lightweight universe?
AB  - How much matter is there in the universe? Does the universe have the critical
      density needed to stop its expansion, or is the universe underweight and destined
      to expand forever? We show that several independent measures, especially those
      utilizing the largest bound systems known-clusters of galaxies-all indicate that
      the mass-density of the universe is insufficient to halt the expansion. A
      promising new method, the evolution of the number density of clusters with time,
      provides the most powerful indication so far that the universe has a subcritical
      density. We show that different techniques reveal a consistent picture of a
      lightweight universe with only approximately 20-30% of the critical density.
      Thus, the universe may expand forever.

PMID- 9600897
TI  - Computer simulations of enzyme catalysis: finding out what has been optimized by
      evolution.
AB  - The origin of the catalytic power of enzymes is discussed, paying attention to
      evolutionary constraints. It is pointed out that enzyme catalysis reflects energy
      contributions that cannot be determined uniquely by current experimental
      approaches without augmenting the analysis by computer simulation studies. The
      use of energy considerations and computer simulations allows one to exclude many
      of the popular proposals for the way enzymes work. It appears that the standard
      approaches used by organic chemists to catalyze reactions in solutions are not
      used by enzymes. This point is illustrated by considering the desolvation
      hypothesis and showing that it cannot account for a large increase in kcat
      relative to the corresponding kcage for the reference reaction in a solvent cage.
      The problems associated with other frequently invoked mechanisms also are
      outlined. Furthermore, it is pointed out that mutation studies are inconsistent
      with ground state destabilization mechanisms. After considering factors that were
      not optimized by evolution, we review computer simulation studies that reproduced
      the overall catalytic effect of different enzymes. These studies pointed toward
      electrostatic effects as the most important catalytic contributions. The nature
      of this electrostatic stabilization mechanism is far from being obvious because
      the electrostatic interaction between the reacting system and the surrounding
      area is similar in enzymes and in solution. However, the difference is that
      enzymes have a preorganized dipolar environment that does not have to pay the
      reorganization energy for stabilizing the relevant transition states. Apparently,
      the catalytic power of enzymes is stored in their folding energy in the form of
      the preorganized polar environment.

PMID- 9600899
TI  - The vibrational energy flow transition in organic molecules: theory meets
      experiment.
AB  - Most large dynamical systems are thought to have ergodic dynamics, whereas small
      systems may not have free interchange of energy between degrees of freedom. This
      assumption is made in many areas of chemistry and physics, ranging from nuclei to
      reacting molecules and on to quantum dots. We examine the transition to facile
      vibrational energy flow in a large set of organic molecules as molecular size is
      increased. Both analytical and computational results based on local random matrix
      models describe the transition to unrestricted vibrational energy flow in these
      molecules. In particular, the models connect the number of states participating
      in intramolecular energy flow to simple molecular properties such as the
      molecular size and the distribution of vibrational frequencies. The transition
      itself is governed by a local anharmonic coupling strength and a local state
      density. The theoretical results for the transition characteristics compare well
      with those implied by experimental measurements using IR fluorescence
      spectroscopy of dilution factors reported by Stewart and McDonald [Stewart, G. M.
      & McDonald, J. D. (1983) J. Chem. Phys. 78, 3907-3915].

PMID- 9600900
TI  - Intramolecular vibrational dephasing obeys a power law at intermediate times.
AB  - Experimental intramolecular vibrational dephasing transients for several large
      organic molecules are reanalyzed. Fits to the experimental data, as well as full
      numerical quantum calculations with a factorized potential surface for all active
      degrees of freedom of fluorene indicate that power law decays, not exponentials,
      occur at intermediate times. The results support a proposal that power law decays
      describe vibrational dephasing dynamics in large molecules at intermediate times
      because of the local nature of energy flow.

PMID- 9600901
TI  - A bait and switch hapten strategy generates catalytic antibodies for
      phosphodiester hydrolysis.
AB  - General base catalysis supplied by the histidine-12 (H-12) residue of
      ribonuclease (RNase) A has long been appreciated as a major component of the
      catalytic power of the enzyme. In an attempt to harness the catalytic power of a
      general base into antibody catalysis of phosphodiester bond hydrolysis, the
      quaternary ammonium phosphate 1 was used as a bait and switch hapten. Based on
      precedence, it was rationalized that this positively charged hapten could induce
      a counter-charged residue in the antibody binding site at a locus suitable for it
      to deprotonate the 2'-hydroxyl group of the anhydroribitol phosphodiester
      substrate 2. After murine immunization with hapten 1, mAb production yielded a
      library of 35 antibodies that bound to a BSA-1 conjugate. From this panel, two
      were found to catalyze the cyclization-cleavage of phosphodiester 2. Kinetic
      studies at pH 7.49 (Hepes, 20 mM) and 25 degreesC showed that the most active
      antibody, MATT.F-1, obeyed classical Michaelis-Menten kinetics with a Km = 104
      microM, a kcat = 0.44 min-1, and a kcat/kuncat = 1.7 x 10(3). Hapten 1
      stoichiometrically inhibits the catalytic activity of the antibody. MATT.F-1 is
      the most proficient antibody-catalyst (1.6 x 10(7) M-1) yet generated for the
      function of phosphodiester hydrolysis and emphasizes the utility of the bait and
      switch hapten paradigm when generating antibody catalysts for processes for which
      general-base catalysis can be exploited.

PMID- 9600902
TI  - Is polarization important in cation-pi interactions?
AB  - The importance of cation->aromatic polarization effects on cation-pi interactions
      has been explored. Theoretical calculations demonstrate that polarization is a
      large contribution to cation-aromatic interactions, and particularly to cation-pi
      interactions. For a series of compounds with a similar aromatic core,
      polarization is constant and makes small influence in the relative cation-binding
      energies. However, when the aromatic core changes polarization contributions
      might be very different. We found that the generalized molecular interaction
      potential with polarization is a very fast and powerful tool for the prediction
      of cation binding of aromatic compounds.

PMID- 9600903
TI  - Submillimolar levels of calcium regulates DNA structure at the dinucleotide
      repeat (TG/AC)n.
AB  - Submillimolar levels of calcium, similar to the physiological total (bound +
      free) intranuclear concentration (0.01-1 mM), induced a conformational change
      within d(TG/AC)n, one of the frequent dinucleotide repeats of the mammalian
      genome. This change is calcium-specific, because no other tested cation induced
      it and it was detected as a concentration-dependent transition from B- to a non-B
      DNA conformation expanding from 3' end toward the 5' of the repeat. Genomic
      footprinting of various rat brain regions revealed the existence of similar non-B
      DNA conformation within a d(TG/AC)28 repeat of the endogenous enkephalin gene
      only in enkephalin-expressing caudate nucleus and not in the nonexpressing
      thalamus. Binding assays demonstrated that DNA could bind calcium and can compete
      with calmodulin for calcium.

PMID- 9600904
TI  - Regulation of sterol regulatory element binding proteins in livers of fasted and
      refed mice.
AB  - Hepatic lipid synthesis is known to be regulated by food consumption. In rodents
      fasting decreases the synthesis of cholesterol as well as fatty acids. Refeeding
      a high carbohydrate/low fat diet enhances fatty acid synthesis by 5- to 20-fold
      above the fed state, whereas cholesterol synthesis returns only to the prefasted
      level. Sterol regulatory element binding proteins (SREBPs) are transcription
      factors that regulate genes involved in cholesterol and fatty acid synthesis.
      Here, we show that fasting markedly reduces the amounts of SREBP-1 and -2 in
      mouse liver nuclei, with corresponding decreases in the mRNAs for SREBP-activated
      target genes. Refeeding a high carbohydrate/low fat diet resulted in a 4- to 5
      fold increase of nuclear SREBP-1 above nonfasted levels, whereas nuclear SREBP-2
      protein returned only to the nonfasted level. The hepatic mRNAs for fatty acid
      biosynthetic enzymes increased 5- to 10-fold above nonfasted levels, a pattern
      that paralleled the changes in nuclear SREBP-1. The hepatic mRNAs for enzymes
      involved in cholesterol synthesis returned to the nonfasted level, closely
      following the pattern of nuclear SREBP-2 regulation. Transgenic mice that
      overproduce nuclear SREBP-1c failed to show the normal decrease in hepatic mRNA
      levels for cholesterol and fatty acid synthetic enzymes upon fasting. We conclude
      that SREBPs are regulated by food consumption in the mouse liver and that the
      decline in nuclear SREBP-1c upon fasting may explain in part the decrease in
      mRNAs encoding enzymes of the fatty acid biosynthetic pathway.

PMID- 9600905
TI  - Two amino acid substitutions convert a guanylyl cyclase, RetGC-1, into an
      adenylyl cyclase.
AB  - Guanylyl cyclases (GCs) and adenylyl cyclases (ACs) have fundamental roles in a
      wide range of cellular processes. Whereas GCs use GTP as a substrate to form
      cGMP, ACs catalyze the analogous conversion of ATP to cAMP. Previously, a model
      based on the structure of adenylate cyclase was used to predict the structure of
      the nucleotide-binding pocket of a membrane guanylyl cyclase, RetGC-1. Based on
      this model, we replaced specific amino acids in the guanine-binding pocket of GC
      with their counterparts from AC. A change of two amino acids, E925K together with
      C995D, is sufficient to completely alter the nucleotide specificity from GTP to
      ATP. These experiments strongly validate the AC-derived RetGC-1 structural model
      and functionally confirm the role of these residues in nucleotide discrimination.

PMID- 9600906
TI  - Crystallographic comparison of the estrogen and progesterone receptor's ligand
      binding domains.
AB  - The 2.8-A crystal structure of the complex formed by estradiol and the human
      estrogen receptor-alpha ligand binding domain (hERalphaLBD) is described and
      compared with the recently reported structure of the progesterone complex of the
      human progesterone receptor ligand binding domain, as well as with similar
      structures of steroid/nuclear receptor LBDs solved elsewhere. The hormone-bound
      hERalphaLBD forms a distinctly different and probably more physiologically
      important dimer interface than its progesterone counterpart. A comparison of the
      specificity determinants of hormone binding reveals a common structural theme of
      mutually supported van der Waals and hydrogen-bonded interactions involving
      highly conserved residues. The previously suggested mechanism by which the
      estrogen receptor distinguishes estradiol's unique 3-hydroxy group from the 3
      keto function of most other steroids is now described in atomic detail. Mapping
      of mutagenesis results points to a coactivator-binding surface that includes the
      region around the "signature sequence" as well as helix 12, where the ligand
      dependent conformation of the activation function 2 core is similar in all
      previously solved steroid/nuclear receptor LBDs. A peculiar crystal packing event
      displaces helix 12 in the hERalphaLBD reported here, suggesting a higher degree
      of dynamic variability than expected for this critical substructure.

PMID- 9600907
TI  - Localization of the Wilson's disease protein product to mitochondria.
AB  - Wilson's disease (WND) is an inherited disorder of copper homeostasis
      characterized by abnormal accumulation of copper in several tissues, particularly
      in the liver, brain, and kidney. The disease-associated gene encodes a copper
      transporting P-type ATPase, the WND protein, the subcellular location of which
      could be regulated by copper. We demonstrate that the WND protein is present in
      cells in two forms, the 160-kDa and the 140-kDa products. The 160-kDa product was
      earlier shown to be targeted to trans-Golgi network. The 140-kDa product
      identified herein is located in mitochondria as evidenced by the
      immunofluorescent staining of HepG2 cells with specific mitochondria markers and
      polyclonal antibody directed against the C terminus of the WND molecule. The
      mitochondrial location for the 140-kDa WND product was confirmed by membrane
      fractionation and by analysis of purified human mitochondria. The antibody raised
      against a repetitive sequence in the N-terminal portion of the WND molecule
      detects an additional 16-kDa protein, suggesting that the 140-kDa product was
      formed after proteolytic cleavage of the full-length WND protein at the N
      terminus. Thus, the WND protein is a P-type ATPase with an unusual subcellular
      localization. The mitochondria targeting of the WND protein suggests its
      important role for copper-dependent processes taking place in this organelle.

PMID- 9600908
TI  - A scrapie-like unfolding intermediate of the prion protein domain PrP(121-231)
      induced by acidic pH.
AB  - The infectious agent of transmissible spongiform encephalopathies is believed to
      consist of an oligomeric isoform, PrPSc, of the monomeric cellular prion protein,
      PrPC. The conversion of PrPC to PrPSc is characterized by a decrease in alpha
      helical structure, an increase in beta-sheet content, and the formation of PrPSc
      amyloid. Whereas the N-terminal part of PrPC comprising residues 23-120 is
      flexibly disordered, its C-terminal part, PrP(121-231), forms a globular domain
      with three alpha-helices and a small beta-sheet. Because the segment of residues
      90-231 is protease-resistant in PrPSc, it is most likely structured in the PrPSc
      form. The conformational change of the segment containing residues 90-120 thus
      constitutes the minimal structural difference between PrPC and a PrPSc monomer.
      To test whether PrP(121-231) is also capable to undergo conformational
      transitions, we analyzed its urea-dependent unfolding transitions at neutral and
      acidic pH. We identified an equilibrium unfolding intermediate of PrP(121-231)
      that is exclusively populated at acidic pH and shows spectral characteristics of
      a beta-sheet protein. The intermediate is in rapid equilibrium with native
      PrP(121-231), significantly populated in the absence of urea at pH 4.0, and may
      have important implications for the presumed formation of PrPSc during
      endocytosis.

PMID- 9600909
TI  - Selective activation of JNK1 is necessary for the anti-apoptotic activity of
      hILP.
AB  - The balance between the inductive signals and endogenous anti-apoptotic
      mechanisms determines whether or not programmed cell death occurs. The widely
      expressed inhibitor of apoptosis gene family includes three closely related
      mammalian proteins: c-IAP1, c-IAP2, and hILP. The anti-apoptotic properties of
      these proteins have been linked to caspase inhibition. Here we show that one
      member of this group, hILP, inhibits interleukin-1beta-converting enzyme-induced
      apoptosis via a mechanism dependent on the selective activation of c-Jun N
      terminal kinase 1. These data demonstrate that apoptosis can be inhibited by an
      endogenous cellular protein by a mechanism that requires the activation of a
      single member of the mitogen-activating protein kinase family.

PMID- 9600910
TI  - Mapping the sigma70 subunit contact sites on Escherichia coli RNA polymerase with
      a sigma70-conjugated chemical protease.
AB  - The core enzyme of Escherichia coli RNA polymerase acquires essential promoter
      recognition and transcription initiation activities by binding one of several
      sigma subunits. To characterize the proximity between sigma70, the major sigma
      for transcription of the growth-related genes, and the core enzyme subunits
      (alpha2 beta beta'), we analyzed the protein-cutting patterns produced by a set
      of covalently tethered FeEDTA probes [FeBABE: Fe (S)-1-(p
      bromoacetamidobenzyl)EDTA]. The probes were positioned in or near conserved
      regions of sigma70 by using seven mutants, each carrying a single cysteine
      residue at position 132, 376, 396, 422, 496, 517, or 581. Each FeBABE-conjugated
      sigma70 was bound to the core enzyme, which led to cleavage of nearby sites on
      the beta and beta' subunits (but not alpha). Unlike the results of random
      cleavage [Greiner, D. P., Hughes, K. A., Gunasekera, A. H. & Meares, C. F. (1996)
      Proc. Natl. Acad. Sci. USA 93, 71-75], the cut sites from different probe
      modified sigma70 proteins are clustered in distinct regions of the subunits. On
      the beta subunit, cleavage is observed in two regions, one between residues 383
      and 554, including the conserved C and Rif regions; and the other between 854 and
      1022, including conserved region G, regions of ppGpp sensitivity, and one of the
      segments forming the catalytic center of RNA polymerase. On the beta' subunit,
      the cleavage was identified within the sequence 228-461, including beta'
      conserved regions C and D (which comprise part of the catalytic center).

PMID- 9600911
TI  - An amino acid as a cofactor for a catalytic polynucleotide.
AB  - Natural ribozymes require metal ion cofactors that aid both in structural folding
      and in chemical catalysis. In contrast, many protein enzymes produce dramatic
      rate enhancements using only the chemical groups that are supplied by their
      constituent amino acids. This fact is widely viewed as the most important feature
      that makes protein a superior polymer for the construction of biological
      catalysts. Herein we report the in vitro selection of a catalytic DNA that uses
      histidine as an active component for an RNA cleavage reaction. An optimized
      deoxyribozyme from this selection requires L-histidine or a closely related
      analog to catalyze RNA phosphoester cleavage, producing a rate enhancement of
      approximately 1-million-fold over the rate of substrate cleavage in the absence
      of enzyme. Kinetic analysis indicates that a DNA-histidine complex may perform a
      reaction that is analogous to the first step of the proposed catalytic mechanism
      of RNase A, in which the imidazole group of histidine serves as a general base
      catalyst. Similarly, ribozymes of the "RNA world" may have used amino acids and
      other small organic cofactors to expand their otherwise limited catalytic
      potential.

PMID- 9600912
TI  - The central structural feature of the membrane fusion protein subunit from the
      Ebola virus glycoprotein is a long triple-stranded coiled coil.
AB  - The ectodomain of the Ebola virus Gp2 glycoprotein was solubilized with a
      trimeric, isoleucine zipper derived from GCN4 (pIIGCN4) in place of the
      hydrophobic fusion peptide at the N terminus. This chimeric molecule forms a
      trimeric, highly alpha-helical, and very thermostable molecule, as determined by
      chemical crosslinking and circular dichroism. Electron microscopy indicates that
      Gp2 folds into a rod-like structure like influenza HA2 and HIV-1 gp41, providing
      further evidence that viral fusion proteins from diverse families such as
      Orthomyxoviridae (Influenza), Retroviridae (HIV-1), and Filoviridae (Ebola) share
      common structural features, and suggesting a common membrane fusion mechanism.

PMID- 9600913
TI  - Stepwise in vitro affinity maturation of Vitaxin, an alphav beta3-specific
      humanized mAb.
AB  - A protein engineering strategy based on efficient and focused mutagenesis
      implemented by codon-based mutagenesis was developed. Vitaxin, a humanized
      version of the antiangiogenic antibody LM609 directed against a conformational
      epitope of the alphav beta3 integrin complex, was used as a model system.
      Specifically, focused mutagenesis was used in a stepwise fashion to rapidly
      improve the affinity of the antigen binding fragment by greater than 90-fold. In
      the complete absence of structural information about the Vitaxin-alphav beta3
      interaction, phage-expressed antibody libraries for all six Ig heavy and light
      chain complementarity-determining regions were expressed and screened by a
      quantitative assay to identify variants with improved binding to alphav beta3.
      The Vitaxin variants in these libraries each contained a single mutation, and all
      20 amino acids were introduced at each complementarity-determining region
      residue, resulting in the expression of 2,336 unique clones. Multiple clones
      displaying 2- to 13-fold improved affinity were identified. Subsequent expression
      and screening of a library of 256 combinatorial variants of the optimal mutations
      identified from the primary libraries resulted in the identification of multiple
      clones displaying greater than 50-fold enhanced affinity. These variants
      inhibited ligand binding to receptor more potently as demonstrated by inhibition
      of cell adhesion and ligand competition assays. Because of the limited
      mutagenesis and combinatorial approach, Vitaxin variants with enhanced affinity
      were identified rapidly and required the synthesis of only 2,592 unique variants.
      The use of such small focused libraries obviates the need for phage affinity
      selection approaches typically used, permitting the use of functional assays and
      the engineering of proteins expressed in mammalian cell culture.

PMID- 9600914
TI  - Intranuclear diffusion and hybridization state of oligonucleotides measured by
      fluorescence correlation spectroscopy in living cells.
AB  - Fluorescein-labeled oligodeoxynucleotides (oligos) were introduced into cultured
      rat myoblasts, and their molecular movements inside the nucleus were studied by
      fluorescence correlation spectroscopy (FCS) and fluorescence recovery after
      photobleaching (FRAP). FCS revealed that a large fraction of both intranuclear
      oligo(dT) (43%) and oligo(dA) (77%) moves rapidly with a diffusion coefficient of
      4 x 10(-7) cm2/s. Interestingly, this rate of intranuclear oligo movement is
      similar to their diffusion rates measured in aqueous solution. In addition, we
      detected a large fraction (45%) of the intranuclear oligo(dT), but not oligo(dA),
      diffusing at slower rates (</=1 x 10(-7) cm2/s). The amount of this slower-moving
      oligo(dT) was greatly reduced if the oligo(dT) was prehybridized in solution with
      (unlabeled) oligo(dA) prior to introduction to cells, presumably because the
      oligo(dT) was then unavailable for subsequent hybridization to endogenous poly(A)
      RNA. The FCS-measured diffusion rate for much of the slower oligo(dT) population
      approximated the diffusion rate in aqueous solution of oligo(dT) hybridized to a
      large polyadenylated RNA (1.0 x 10(-7) cm2/s). Moreover, this intranuclear
      movement rate falls within the range of calculated diffusion rates for an average
      sized heterogeneous nuclear ribonucleoprotein particle in aqueous solution. A
      subfraction of oligo(dT) (15%) moved over 10-fold more slowly, suggesting it was
      bound to very large macromolecular complexes. Average diffusion coefficients
      obtained from FRAP experiments were in agreement with the FCS data. These results
      demonstrate that oligos can move about within the nucleus at rates comparable to
      those in aqueous solution and further suggest that this is true for large
      ribonucleoprotein complexes as well.

PMID- 9600915
TI  - DNA annealing by RAD52 protein is stimulated by specific interaction with the
      complex of replication protein A and single-stranded DNA.
AB  - Homologous recombination in Saccharomyces cerevisiae depends critically on RAD52
      function. In vitro, Rad52 protein preferentially binds single-stranded DNA
      (ssDNA), mediates annealing of complementary ssDNA, and stimulates Rad51 protein
      mediated DNA strand exchange. Replication protein A (RPA) is a ssDNA-binding
      protein that is also crucial to the recombination process. Herein we report that
      Rad52 protein effects the annealing of RPA-ssDNA complexes, complexes that are
      otherwise unable to anneal. The ability of Rad52 protein to promote annealing
      depends on both the type of ssDNA substrate and ssDNA binding protein. RPA
      allows, but slows, Rad52 protein-mediated annealing of oligonucleotides. In
      contrast, RPA is almost essential for annealing of longer plasmid-sized DNA but
      has little effect on the annealing of poly(dT) and poly(dA), which are relatively
      long DNA molecules free of secondary structure. These results suggest that one
      role of RPA in Rad52 protein-mediated annealing is the elimination of DNA
      secondary structure. However, neither Escherichia coli ssDNA binding protein nor
      human RPA can substitute in this reaction, indicating that RPA has a second role
      in this process, a role that requires specific RPA-Rad52 protein interactions.
      This idea is confirmed by the finding that RPA, which is complexed with
      nonhomologous ssDNA, inhibits annealing but the human RPA-ssDNA complex does not.
      Finally, we present a model for the early steps of the repair of double-strand
      DNA breaks in yeast.

PMID- 9600916
TI  - Nonneuronal isoforms of STOP protein are responsible for microtubule cold
      stability in mammalian fibroblasts.
AB  - A number of cycling mammalian cells, such as NIH 3T3, contain abundant subsets of
      cold-stable microtubules. The origin of such microtubule stabilization in
      nonneuronal cells is unknown. We have previously described a neuronal protein,
      stable tubule-only polypeptide (STOP), that binds to microtubules and induces
      cold stability. We find that NIH 3T3 fibroblasts contain a major 42-kDa isoform
      of STOP (fibroblastic STOP, F-STOP). F-STOP contains the central repeats
      characteristic of brain STOP but shows extensive deletions of N- and C-terminal
      protein domains that are present in brain STOP. These deletions arise from
      differences in STOP RNA splicing. Despite such deletions, F-STOP has full
      microtubule stabilizing activity. F-STOP accumulates on cold-stable microtubules
      of interphase arrays and is present on stable microtubules within the mitotic
      spindle of NIH 3T3 cells. STOP inhibition by microinjection of affinity-purified
      STOP central repeat antibodies into NIH 3T3 cells abolishes both interphase and
      spindle microtubule cold stability. Similar results were obtained with Rat2
      cells. These results show that STOP proteins have nonneuronal isoforms that are
      responsible for the microtubule cold stability observed in mammalian fibroblasts.

PMID- 9600917
TI  - Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction
      with Ob receptor.
AB  - Leptin is an adipocyte-derived cytokine that regulates food intake and body
      weight via interaction with its Ob receptor (ObR). Serum leptin levels are
      chronically elevated in obese humans, suggesting that obesity may be associated
      with leptin resistance and the inability to generate an adequate ObR response.
      Evidence suggests that transcriptional activation of target genes by STAT3
      (signal transducer and activator of transcription) in the hypothalamus is a
      critical pathway that mediates leptin's action. Herein we report that activation
      of ObR induces the tyrosine phosphorylation of the tyrosine phosphatase SH2
      containing phosphatase 2 (SHP-2) and demonstrate that Tyr986 within the ObR
      cytoplasmic domain is essential to mediate phosphorylation of SHP-2 and binding
      of SHP-2 to ObR. Surprisingly, mutation of Tyr986 to Phe, which abrogates SHP-2
      phosphorylation and binding to the receptor, dramatically increases gene
      induction mediated by STAT3. Our findings indicate that SHP-2 is a negative
      regulator of STAT3-mediated gene induction after activation of ObR and raise the
      possibility that blocking the interaction of SHP-2 with ObR could overcome leptin
      resistance by boosting leptin's weight-reducing effects in obese individuals.

PMID- 9600918
TI  - Translation inhibitors stabilize Escherichia coli mRNAs independently of ribosome
      protection.
AB  - Translation inhibitors such as chloramphenicol in prokaryotes or cycloheximide in
      eukaryotes stabilize many or most cellular mRNAs. In Escherichia coli, this
      stabilization is ascribed generally to the shielding of mRNAs by stalled
      ribosomes. To evaluate this interpretation, we examine here how inhibitors affect
      the stabilities of two untranslated RNAs, i.e., an engineered lacZ mRNA lacking a
      ribosome binding site, and a small regulatory RNA, RNAI. Whether they block
      elongation or initiation, all translation inhibitors tested stabilized these
      RNAs, indicating that stabilization does not necessarily reflect changes in
      packing or activity of translating ribosomes. Moreover, both the initial RNase E
      dependent cleavage of RNAI and lacZ mRNA and the subsequent attack of RNAI by
      polynucleotide phosphorylase and poly(A)-polymerase were slowed. Among various
      possible mechanisms for this stabilization, we discuss in particular a passive
      model. When translation is blocked, rRNA synthesis is known to increase
      severalfold and rRNA becomes unstable. Meanwhile, the pools of RNase E and
      polynucleotide phosphorylase, which, in growing cells, are limited because these
      RNases autoregulate their own synthesis, cannot expand. The
      processing/degradation of newly synthesized rRNA would then titrate these RNases,
      causing bulk mRNA stabilization.

PMID- 9600919
TI  - Assessing sequence comparison methods with reliable structurally identified
      distant evolutionary relationships.
AB  - Pairwise sequence comparison methods have been assessed using proteins whose
      relationships are known reliably from their structures and functions, as
      described in the SCOP database [Murzin, A. G., Brenner, S. E., Hubbard, T. &
      Chothia C. (1995) J. Mol. Biol. 247, 536-540]. The evaluation tested the programs
      BLAST [Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J.
      (1990). J. Mol. Biol. 215, 403-410], WU-BLAST2 [Altschul, S. F. & Gish, W. (1996)
      Methods Enzymol. 266, 460-480], FASTA [Pearson, W. R. & Lipman, D. J. (1988)
      Proc. Natl. Acad. Sci. USA 85, 2444-2448], and SSEARCH [Smith, T. F. & Waterman,
      M. S. (1981) J. Mol. Biol. 147, 195-197] and their scoring schemes. The error
      rate of all algorithms is greatly reduced by using statistical scores to evaluate
      matches rather than percentage identity or raw scores. The E-value statistical
      scores of SSEARCH and FASTA are reliable: the number of false positives found in
      our tests agrees well with the scores reported. However, the P-values reported by
      BLAST and WU-BLAST2 exaggerate significance by orders of magnitude. SSEARCH,
      FASTA ktup = 1, and WU-BLAST2 perform best, and they are capable of detecting
      almost all relationships between proteins whose sequence identities are >30%. For
      more distantly related proteins, they do much less well; only one-half of the
      relationships between proteins with 20-30% identity are found. Because many
      homologs have low sequence similarity, most distant relationships cannot be
      detected by any pairwise comparison method; however, those which are identified
      may be used with confidence.

PMID- 9600920
TI  - Identification of an additional negative regulatory region for p53 sequence
      specific DNA binding.
AB  - The DNA binding activity of p53 is crucial for its tumor suppressor function and
      is subject to tight regulation. Previous studies revealed that the inhibitory
      function of the p53 C terminus is implicated in the latent, low affinity sequence
      specific DNA binding activity of p53 in the uninduced state. Sequence-specific
      DNA binding of p53 has been shown to be activated by several posttranslational
      modifications and interacting proteins that target predominantly the C terminus.
      Moreover, several authors have shown that synthetic peptides corresponding to p53
      C-terminal sequences activate p53 sequence-specific DNA binding. In an effort to
      identify the interaction site of p53 with these activating peptides we assessed
      complex formation between p53 deletion constructs and C-terminal activating
      peptides by peptide affinity precipitation. This study revealed that two distal
      regions of the p53 molecule contribute synergistically to the interaction with
      activating C-terminal peptides: amino acids 80-93 and 364-393. The C-terminal
      residues 364-393 are already well characterized as having negative regulatory
      function. DNA binding analyses with these deletion constructs reveal a comparable
      negative regulatory activity for residues 80-93, defining this region as a
      previously unidentified negative regulatory domain of p53. Furthermore, synthetic
      peptides spanning this newly identified proline-rich negative regulatory region
      (residues 80-93) are able to activate p53 sequence-specific DNA binding in vitro.
      We suggest that both negative regulatory regions, residues 80-93 and 364-393,
      contribute cooperatively to the maintenance of the latent, low-affinity DNA
      binding conformation of p53.

PMID- 9600921
TI  - PU.1 as an essential activator for the expression of gp91(phox) gene in human
      peripheral neutrophils, monocytes, and B lymphocytes.
AB  - We have reported a deficiency of a 91-kDa glycoprotein component of the phagocyte
      NADPH oxidase (gp91(phox)) in neutrophils, monocytes, and B lymphocytes of a
      patient with X chromosome-linked chronic granulomatous disease. Sequence analysis
      of his gp91(phox) gene revealed a single-base mutation (C --> T) at position -53.
      Electrophoresis mobility-shift assays showed that both PU.1 and hematopoietic
      associated factor 1 (HAF-1) bound to the inverted PU.1 consensus sequence
      centered at position -53 of the gp91(phox) promoter, and the mutation at position
      -53 strongly inhibited the binding of both factors. It was also indicated that a
      mutation at position -50 strongly inhibited PU.1 binding but hardly inhibited HAF
      1 binding, and a mutation at position -56 had an opposite binding specificity for
      these factors. In transient expression assay using HEL cells, which express PU.1
      and HAF-1, the mutations at positions -53 and -50 significantly reduced the
      gp91(phox) promoter activity; however, the mutation at position -56 did not
      affect the promoter activity. In transient cotransfection study, PU.1
      dramatically activated the gp91(phox) promoter in Jurkat T cells, which
      originally contained HAF-1 but not PU.1. In addition, the single-base mutation (C
      --> T) at position -52 that was identified in a patient with chronic
      granulomatous disease inhibited the binding of PU.1 to the promoter. We therefore
      conclude that PU.1 is an essential activator for the expression of gp91(phox)
      gene in human neutrophils, monocytes, and B lymphocytes.

PMID- 9600922
TI  - Structural basis for heterogeneous kinetics: reengineering the hairpin ribozyme.
AB  - The RNA cleavage reaction catalyzed by the hairpin ribozyme shows biphasic
      kinetics, and chase experiments show that the slow phase of the reaction results
      from reversible substrate binding to an inactive conformational isomer. To
      investigate the structural basis for the heterogeneous kinetics, we have
      developed an enzymatic RNA modification method that selectively traps substrate
      bound to the inactive conformer and allows the two forms of the ribozyme
      substrate complex to be separated and analyzed by using both physical and kinetic
      strategies. The inactive form of the complex was trapped by the addition of T4
      RNA ligase to a cleavage reaction, resulting in covalent linkage of the 5' end of
      the substrate to the 3' end of the ribozyme and in selective and quantitative
      ablation of the slow kinetic phase of the reaction. This result indicates that
      the inactive form of the ribozyme-substrate complex can adopt a conformation in
      which helices 2 and 3 are coaxially stacked, whereas the active form does not
      have access to this conformation, because of a sharp bend at the helical junction
      that presumably is stabilized by inter-domain tertiary contacts required for
      catalytic activity. These results were used to improve the activity of the
      hairpin ribozyme by designing new interfaces between the two domains, one
      containing a non-nucleotidic orthobenzene linkage and the other replacing the two
      way junction with a three-way junction. Each of these modified ribozymes
      preferentially adopts the active conformation and displays improved catalytic
      efficiency.

PMID- 9600923
TI  - Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the
      photoactive pigments for setting the circadian clock in mammals.
AB  - In mammals the retina contains photoactive molecules responsible for both vision
      and circadian photoresponse systems. Opsins, which are located in rods and cones,
      are the pigments for vision but it is not known whether they play a role in
      circadian regulation. A subset of retinal ganglion cells with direct projections
      to the suprachiasmatic nucleus (SCN) are at the origin of the retinohypothalamic
      tract that transmits the light signal to the master circadian clock in the SCN.
      However, the ganglion cells are not known to contain rhodopsin or other opsins
      that may function as photoreceptors. We have found that the two blue-light
      photoreceptors, cryptochromes 1 and 2 (CRY1 and CRY2), recently discovered in
      mammals are specifically expressed in the ganglion cell and inner nuclear layers
      of the mouse retina. In addition, CRY1 is expressed at high level in the SCN and
      oscillates in this tissue in a circadian manner. These data, in conjunction with
      the established role of CRY2 in photoperiodism in plants, lead us to propose that
      mammals have a vitamin A-based photopigment (opsin) for vision and a vitamin B2
      based pigment (cryptochrome) for entrainment of the circadian clock.

PMID- 9600924
TI  - Free energy of burying hydrophobic residues in the interface between protein
      subunits.
AB  - We have obtained an experimental estimate of the free energy change associated
      with variations at the interface between protein subunits, a subject that has
      raised considerable interest since the concept of accessible surface area was
      introduced by Lee and Richards [Lee, B. & Richards, F. M. (1971) J. Mol. Biol.
      55, 379-400]. We determined by analytical ultracentrifugation the dimer-tetramer
      equilibrium constant of five single and three double mutants of human Hb. One
      mutation is at the stationary alpha1 beta1 interface, and all of the others are
      at the sliding alpha1 beta2 interface where cleavage of the tetramer into dimers
      and ligand-linked allosteric changes are known to occur. A surprisingly good
      linear correlation between the change in the free energy of association of the
      mutants and the change in buried hydrophobic surface area was obtained, after
      corrections for the energetic cost of losing steric complementarity at the
      alphabeta dimer interface. The slope yields an interface stabilization free
      energy of -15 +/- 1.2 cal/mol upon burial of 1 A2 of hydrophobic surface, in very
      good agreement with the theoretical estimate given by Eisenberg and McLachlan
      [Eisenberg, D. & McLachlan, A. D. (1986) Nature (London) 319, 199-203].

PMID- 9600925
TI  - Role of the J-domain in the cooperation of Hsp40 with Hsp70.
AB  - The Escherichia coli Hsp40 DnaJ and Hsp70 DnaK cooperate in the binding of
      proteins at intermediate stages of folding, assembly, and translocation across
      membranes. Binding of protein substrates to the DnaK C-terminal domain is
      controlled by ATP binding and hydrolysis in the N-terminal ATPase domain. The
      interaction of DnaJ with DnaK is mediated at least in part by the highly
      conserved N-terminal J-domain of DnaJ that includes residues 2-75. Heteronuclear
      NMR experiments with uniformly 15N-enriched DnaJ2-75 indicate that the chemical
      environment of residues located in helix II and the flanking loops is perturbed
      on interaction with DnaK or a truncated DnaK molecule, DnaK2-388. NMR signals
      corresponding to these residues broaden and exhibit changes in chemical shifts in
      the presence of DnaK(MgADP). Addition of MgATP largely reversed the broadening,
      indicating that NMR signals of DnaJ2-75 respond to ATP-dependent changes in DnaK.
      The J-domain interaction is localized to the ATPase domain of DnaK and is likely
      to be dominated by electrostatic interactions. The results suggest that the J
      domain tethers DnaK to DnaJ-bound substrates, which DnaK then binds with its C
      terminal peptide-binding domain.

PMID- 9600926
TI  - Fourier transform infrared spectroscopy reveals a rigid alpha-helical assembly
      for the tetrameric Streptomyces lividans K+ channel.
AB  - The structure of the tetrameric K+ channel from Streptomyces lividans in a lipid
      bilayer environment was studied by polarized attenuated total reflection Fourier
      transform infrared spectroscopy. The channel displays approximately 43% alpha
      helical and 25% beta-sheet content. In addition, H/D exchange experiments show
      that only 43% of the backbone amide protons are exchangeable with solvent. On
      average, the alpha-helices are tilted 33 degrees normal to the membrane surface.
      The results are discussed in relationship to the lactose permease of Escherichia
      coli, a membrane transport protein.

PMID- 9600927
TI  - Huntingtin aggregation monitored by dynamic light scattering.
AB  - An initial stage of fibrillogenesis in solutions of glutathione S-transferase
      huntingtin (GST-HD) fusion proteins has been studied by using dynamic light
      scattering. Two GST-HD systems with poly-L-glutamine (polyGln) extensions of
      different lengths (20 and 51 residues) have been examined. For both systems,
      kinetics of z-average translation diffusion coefficients (Dapp) and their angular
      dependence have been obtained. Our data reveal that aggregation does occur in
      both GST-HD51 and GST-HD20 solutions, but that it is much more pronounced in the
      former. Thus, our approach provides a powerful tool for the quantitative assay of
      GST-HD fibrillogenesis in vitro.

PMID- 9600928
TI  - Sulfur K-edge x-ray absorption spectroscopy: a spectroscopic tool to examine the
      redox state of S-containing metabolites in vivo.
AB  - The sulfur K-edge x-ray absorption spectra for the amino acids cysteine and
      methionine and their corresponding oxidized forms cystine and methionine
      sulfoxide are presented. Distinct differences in the shape of the edge and the
      inflection point energy for cysteine and cystine are observed. For methionine
      sulfoxide the inflection point energy is 2.8 eV higher compared with methionine.
      Glutathione, the most abundant thiol in animal cells, also has been investigated.
      The x-ray absorption near-edge structure spectrum of reduced glutathione
      resembles that of cysteine, whereas the spectrum of oxidized glutathione
      resembles that of cystine. The characteristic differences between the thiol and
      disulfide spectra enable one to determine the redox status (thiol to disulfide
      ratio) in intact biological systems, such as unbroken cells, where glutathione
      and cyst(e)ine are the two major sulfur-containing components. The sulfur K-edge
      spectra for whole human blood, plasma, and erythrocytes are shown. The
      erythrocyte sulfur K-edge spectrum is similar to that of fully reduced
      glutathione. Simulation of the plasma spectrum indicated 32% thiol and 68%
      disulfide sulfur. The whole blood spectrum can be simulated by a combination of
      46% disulfide and 54% thiol sulfur.

PMID- 9600929
TI  - The nature of the excited state of the reaction center of photosystem II of green
      plants: a high-resolution fluorescence spectroscopy study.
AB  - We studied the electronically excited state of the isolated reaction center of
      photosystem II with high-resolution fluorescence spectroscopy at 5 K and compared
      the obtained spectral features with those obtained earlier for the primary
      electron donor. The results show that there is a striking resemblance between the
      emitting and charge-separating states in the photosystem II reaction center, such
      as a very similar shape of the phonon wing with characteristic features at 19 and
      80 cm-1, almost identical frequencies of a number of vibrational modes, a very
      similar double-Gaussian shape of the inhomogeneous distribution function, and
      relatively strong electron-phonon coupling for both states. We suggest that the
      emission at 5 K originates either from an exciton state delocalized over the
      inactive branch of the photosystem or from a fraction of the primary electron
      donor that is long-lived at 5 K. The latter possibility can be explained by a
      distribution of the free energy difference of the primary charge separation
      reaction around zero. Both possibilities are in line with the idea that the state
      that drives primary charge separation in the reaction center of photosystem II is
      a collective state, with contributions from all chlorophyll molecules in the
      central part of the complex.

PMID- 9600930
TI  - Visualization of elongation factor G on the Escherichia coli 70S ribosome: the
      mechanism of translocation.
AB  - During protein synthesis, elongation factor G (EF-G) binds to the ribosome and
      promotes the step of translocation, a process in which tRNA moves from the A to
      the P site of the ribosome and the mRNA is advanced by one codon. By using three
      dimensional cryo-electron microscopy, we have visualized EF-G in a ribosome-EF-G
      GDP-fusidic acid complex. Fitting the crystal structure of EF-G-GDP into the cryo
      density map reveals a large conformational change mainly associated with domain
      IV, the domain that mimics the shape of the anticodon arm of the tRNA in the
      structurally homologous ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog.
      The tip portion of this domain is found in a position that overlaps the anticodon
      arm of the A-site tRNA, whose position in the ribosome is known from a study of
      the pretranslocational complex, implying that EF-G displaces the A-site tRNA to
      the P site by physical interaction with the anticodon arm.

PMID- 9600931
TI  - Differential expression of dystrophin isoforms and utrophin during dibutyryl-cAMP
      induced morphological differentiation of rat brain astrocytes.
AB  - We have identified isoforms of dystrophin and utrophin, a dystrophin homologue,
      expressed in astrocytes and examined their expression patterns during dibutyryl
      cAMP (dBcAMP)-induced morphological differentiation of astrocytes. Immunoblot and
      immunocytochemical analyses showed that full-length-type dystrophin (427 kDa),
      utrophin (395 kDa), and Dp71 (75 kDa), a small-type dystrophin isoform, were
      coexpressed in cultured nondifferentiated rat brain astrocytes and were found to
      be located in the cell membrane. During morphological differentiation of the
      astrocytes induced by 1 mM dBcAMP, the amount of Dp71 markedly increased, whereas
      that of dystrophin and utrophin decreased. Northern blot analyses revealed that
      dBcAMP regulates the mRNA levels of Dp71 and dystrophin but not that of utrophin.
      dBcAMP slightly increased the amount of the beta-dystroglycan responsible for
      anchoring dystrophin isoforms and utrophin to the cell membrane.
      Immunocytochemical analyses showed that most utrophin was observed in the
      cytoplasmic area during astrocyte differentiation, whereas Dp71 was found along
      the cell membrane of the differentiated astrocytes. These findings suggest that
      most of the dystrophin/utrophin-dystroglycan complex on cell membrane in cultured
      astrocytes was replaced by the Dp71-dystroglycan complex during morphological
      differentiation. The cell biological roles of Dp71 are discussed.

PMID- 9600932
TI  - In situ activation of the type 2 ryanodine receptor in pancreatic beta cells
      requires cAMP-dependent phosphorylation.
AB  - Molecular mechanisms that regulate in situ activation of ryanodine receptors (RY)
      in different cells are poorly understood. Here we demonstrate that caffeine (10
      mM) released Ca2+ from the endoplasmic reticulum (ER) in the form of small spikes
      in only 14% of cultured fura-2 loaded beta cells from ob/ob mice. Surprisingly,
      when forskolin, an activator of adenylyl cyclase was present, caffeine induced
      larger Ca2+ spikes in as many as 60% of the cells. Forskolin or the
      phosphodiesterase-resistant PKA activator Sp-cAMPS alone did not release Ca2+
      from ER. 4-Chloro-3-ethylphenol (4-CEP), an agent that activates RYs in other
      cell systems, released Ca2+ from ER, giving rise to a slow and small increase in
      [Ca2+]i in beta cells. Prior exposure of cells to forskolin or caffeine (5 mM)
      qualitatively altered Ca2+ release by 4-CEP, giving rise to Ca2+ spikes. In
      glucose-stimulated beta cells forskolin induced Ca2+ spikes that were enhanced by
      3,9-dimethylxanthine, an activator of RYs. Analysis of RNA from islets and
      insulin-secreting betaTC-3-cells by RNase protection assay, using type-specific
      RY probes, revealed low-level expression of mRNA for the type 2 isoform of the
      receptor (RY2). We conclude that in situ activation of RY2 in beta cells requires
      cAMP-dependent phosphorylation, a process that recruits the receptor in a
      functionally operative form.

PMID- 9600933
TI  - A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates
      multiple cellular responses to lysophosphatidic acid.
AB  - Extracellular lysophosphatidic acid (LPA) produces diverse cellular responses in
      many cell types. Recent reports of several molecularly distinct G protein-coupled
      receptors have raised the possibility that the responses to LPA stimulation could
      be mediated by the combination of several uni-functional receptors. To address
      this issue, we analyzed one receptor encoded by ventricular zone gene-1 (vzg-1)
      (also referred to as lpA1/edg-2) by using heterologous expression in a neuronal
      and nonneuronal cell line. VZG-1 expression was necessary and sufficient in
      mediating multiple effects of LPA: [3H]-LPA binding, G protein activation, stress
      fiber formation, neurite retraction, serum response element activation, and
      increased DNA synthesis. These results demonstrate that a single receptor,
      encoded by vzg-1, can activate multiple LPA-dependent responses in cells from
      distinct tissue lineages.

PMID- 9600934
TI  - Efficient construction of a large nonimmune phage antibody library: the
      production of high-affinity human single-chain antibodies to protein antigens.
AB  - A large library of phage-displayed human single-chain Fv antibodies (scFv),
      containing 6.7 x 10(9) members, was generated by improving the steps of library
      construction. Fourteen different protein antigens were used to affinity select
      antibodies from this library. A panel of specific antibodies was isolated with
      each antigen, and each panel contained an average of 8.7 different scFv.
      Measurements of antibody-antigen interactions revealed several affinities below 1
      nM, comparable to affinities observed during the secondary murine immune
      response. In particular, four different scFv recognizing the ErbB2 protein had
      affinities ranging from 220 pM to 4 nM. Antibodies derived from the library
      proved to be useful reagents for immunoassays. For example, antibodies generated
      to the Chlamydia trachomatis elementary bodies stained Chlamydia-infected cells,
      but not uninfected cells. These results demonstrate that phage antibody libraries
      are ideally suited for the rapid production of panels of high-affinity mAbs to a
      wide variety of protein antigens. Such libraries should prove especially useful
      for generating reagents to study the function of gene products identified by
      genome projects.

PMID- 9600936
TI  - Tyrosine kinase-dependent activation of a chloride channel in CD95-induced
      apoptosis in T lymphocytes.
AB  - CD95/Fas/APO-1 mediated apoptosis is an important mechanism in the regulation of
      the immune response. Here, we show that CD95 receptor triggering activates an
      outwardly rectifying chloride channel (ORCC) in Jurkat T lymphocytes. Ceramide, a
      lipid metabolite synthesized upon CD95 receptor triggering, also induces
      activation of ORCC in cell-attached patch clamp experiments. Activation is
      mediated by Src-like tyrosine kinases, because it is abolished by the tyrosine
      kinase inhibitor herbimycin A or by genetic deficiency of p56lck. In vitro
      incubation of excised patches with purified p56lck results in activation of ORCC,
      which is partially reversed upon addition of anti-phosphotyrosine antibody.
      Inhibition of ORCC by four different drugs correlates with a 30-65% inhibition of
      apoptosis. Intracellular acidification observed upon CD95 triggering is abolished
      by inhibition of either ORCC or p56lck. The results suggest that tyrosine kinase
      mediated activation of ORCC may play a role in CD95-induced cell death in T
      lymphocytes.

PMID- 9600935
TI  - p53-Dependent and -independent responses to cisplatin in mouse testicular
      teratocarcinoma cells.
AB  - Testicular cancers respond favorably to chemotherapy with the platinum-containing
      drug cis-diamminedichloroplatinum(II) (cisplatin). One factor that could explain
      the efficacy of cisplatin is the low frequency of p53 mutations observed in this
      tumor type. The present study examines the p53-mediated responses in murine
      testicular teratocarcinoma cells exposed to the drug. Cisplatin treatment of
      teratocarcinoma cells with a wild-type p53 gene resulted in accumulation of the
      p53 protein through posttranscriptional mechanisms; induction of p53-target genes
      was also observed. Drug treatment resulted in rapid apoptosis in p53-wild-type
      cells but not in p53(-/-) teratocarcinoma cells. In the latter cells, cisplatin
      exposure caused prolonged cell cycle arrest accompanied by induction of the p21
      gene. Clonogenic assays demonstrated that the p53 mutation did not confer
      resistance to cisplatin. These experiments suggest that cisplatin inhibits
      cellular proliferation of testicular teratocarcinoma cells by two possible
      mechanisms, p53-dependent apoptosis and p53-independent cell cycle arrest.

PMID- 9600937
TI  - Transcytosis of alpha1-acidic glycoprotein in the continuous microvascular
      endothelium.
AB  - By using perfusions and bolus administration, coupled with postembedding
      immunocytochemical procedures, we have identified the structures involved in the
      transport of derivatized orosomucoid (alpha1-acidic glycoprotein) across the
      continuous microvascular endothelium of the murine myocardium. Our findings
      indicate that: (i) monomeric orosomucoid binds to the luminal surface of the
      endothelium; (ii) it is restricted to caveolae during its transport across the
      endothelium; (iii) it is detected in the perivascular spaces at early time points
      (by 1 min) and in larger quantities at later time points (>5 min) from the
      beginning of its perfusion or its intravascular administration; (iv) no
      orosomucoid molecules are found in the intercellular junctions or at the
      abluminal exits of interendothelial spaces; and (v) the vesicular transport of
      orosomucoid is strongly inhibited by N-ethylmaleimide (>80%). Because, by size
      and shape, the orosomucoid qualifies as a preferential probe for the postulated
      small pore system, our results are discussed in relation to the pore theory of
      capillary permeability.

PMID- 9600938
TI  - The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed
      end capping, and formation of branching networks of filaments.
AB  - The Arp2/3 complex is a stable assembly of seven protein subunits including two
      actin-related proteins (Arp2 and Arp3) and five novel proteins. Previous work
      showed that this complex binds to the sides of actin filaments and is
      concentrated at the leading edges of motile cells. Here, we show that Arp2/3
      complex purified from Acanthamoeba caps the pointed ends of actin filaments with
      high affinity. Arp2/3 complex inhibits both monomer addition and dissociation at
      the pointed ends of actin filaments with apparent nanomolar affinity and
      increases the critical concentration for polymerization at the pointed end from
      0.6 to 1.0 microM. The high affinity of Arp2/3 complex for pointed ends and its
      abundance in amoebae suggest that in vivo all actin filament pointed ends are
      capped by Arp2/3 complex. Arp2/3 complex also nucleates formation of actin
      filaments that elongate only from their barbed ends. From kinetic analysis, the
      nucleation mechanism appears to involve stabilization of polymerization
      intermediates (probably actin dimers). In electron micrographs of quick-frozen,
      deep-etched samples, we see Arp2/3 bound to sides and pointed ends of actin
      filaments and examples of Arp2/3 complex attaching pointed ends of filaments to
      sides of other filaments. In these cases, the angle of attachment is a remarkably
      constant 70 +/- 7 degrees. From these in vitro biochemical properties, we propose
      a model for how Arp2/3 complex controls the assembly of a branching network of
      actin filaments at the leading edge of motile cells.

PMID- 9600939
TI  - Hydrolysis of GTP on rab11 is required for the direct delivery of transferrin
      from the pericentriolar recycling compartment to the cell surface but not from
      sorting endosomes.
AB  - Rab11 is a small GTP-binding protein that in cultured mammalian cells has been
      shown to be concentrated in the pericentriolar endosomal recycling compartment
      and to play a key role in passage of the recycling transferrin receptor through
      that compartment [Ullrich, O., Reinsch, S., Urbe, S., Zerial, M. & Parton, R. G.
      (1996) J. Cell Biol. 135, 913-924]. To obtain insights into the site(s) of action
      of rab11 within the recycling pathway, we have now compared the effects on
      recycling at 37 degreesC of overexpression of wild-type rab11 and various mutant
      forms of this protein in cells that had been loaded with transferrin at either 37
      degreesC or 16 degreesC. We show that incubation at 16 degreesC blocks passage of
      endocytosed transferrin into the recycling compartment and that, whereas the
      rab11 dominant negative mutant form (S25N) inhibits transferrin recycling after
      interiorization at either temperature, the wild-type rab11 and constitutively
      active mutant (Q70L) have no inhibitory effect on the recycling of molecules that
      were interiorized at 16 degreesC. This differential inhibitory effect shows that
      two distinct pathways for recycling are followed by the bulk of the transferrin
      molecules interiorized at the two different temperatures. The incapacity of the
      constitutively active form of rab11 (Q70L) to inhibit recycling of molecules
      interiorized at 16 degreesC is consistent with their recycling taking place
      directly from sorting endosomes, in a process that does not require hydrolysis of
      GTP on rab11. The fact that the dominant negative (S25N) form of rab11 inhibits
      recycling of molecules interiorized at both temperatures indicates that
      activation of rab11 by GTP is required for exit of transferrin from sorting
      endosomes, regardless of whether this exit is toward the recycling compartment or
      directly to the plasma membrane.

PMID- 9600940
TI  - Inactivation of the mouse sperm receptor, mZP3, by site-directed mutagenesis of
      individual serine residues located at the combining site for sperm.
AB  - To initiate fertilization, mouse sperm bind to Ser- (O-) linked oligosaccharides
      located at the sperm combining site of zona pellucida glycoprotein mZP3.
      Apparently, the oligosaccharides are present on one or more of five Ser residues
      clustered in the carboxyl-terminal region of the mZP3 polypeptide. Here, each of
      the Ser residues, as well as an intervening Asn residue, was converted to a
      small, nonhydroxy amino acid by site-directed mutagenesis. Mouse embryonal
      carcinoma (EC) cells were then stably transfected with the wild-type and mutated
      mZP3 genes. In each case, transfected cells synthesized and secreted recombinant
      EC-mZP3 into the culture medium. The glycoproteins were partially purified and
      assayed for their ability to inhibit binding of sperm to ovulated eggs in vitro.
      As compared with wild-type EC-mZP3, mutations of Ser-329, Ser-331, or Ser-333 had
      no effect on sperm receptor activity. Mutation of Asn-330, a potential N-linked
      glycosylation site, also had no effect on sperm receptor activity. On the other
      hand, mutation of either Ser-332 or Ser-334, or mutation of Ser-332, Ser-333, and
      Ser-334, resulted in complete inactivation of EC-mZP3 as a sperm receptor. These
      results suggest that Ser-332 and Ser-334, residues conserved in mouse, hamster,
      and human ZP3, are essential for sperm receptor activity.

PMID- 9600942
TI  - Directed seed dispersal by bellbirds in a tropical cloud forest.
AB  - A fundamental goal of plant population ecology is to understand the consequences
      for plant fitness of seed dispersal by animals. Theories of seed dispersal and
      tropical forest regeneration suggest that the advantages of seed dispersal for
      most plants are escape from seed predation near the parent tree and colonization
      of vacant sites, the locations of which are unpredictable in space and time. Some
      plants may gain in fitness as a fortuitous consequence of disperser behavior if
      certain species of dispersers nonrandomly place seeds in sites predictably
      favorable for seedling establishment. Such patterns of directed dispersal by
      vertebrates long have been suggested but never demonstrated for tropical forest
      trees. Here we report the pattern of seed distribution and 1-year seedling
      survival generated by five species of birds for a neotropical, shade-tolerant
      tree. Four of the species dispersed seeds to sites near the parent trees with
      microhabitat characteristics similar to those at random locations, whereas the
      fifth species, a bellbird, predictably dispersed seeds under song perches in
      canopy gaps. The pattern of seedling recruitment was bimodal, with a peak near
      parent trees and a second peak, corresponding to bellbird song perches, far (>40
      m) from parent trees. Seedling survival was higher for seeds dispersed by
      bellbirds than by the other species, because of a reduction in seedling mortality
      by fungal pathogens in gaps. Thus, bellbirds play a significant role in seed
      dispersal by providing directed dispersal to favorable sites and therefore may
      influence plant recruitment patterns and species diversity in Neotropical
      forests.

PMID- 9600941
TI  - Expression of the mouse cerberus-related gene, Cerr1, suggests a role in anterior
      neural induction and somitogenesis.
AB  - The Xenopus cerberus gene encodes a secreted factor that is expressed in the
      anterior endomesoderm of gastrula stage embryos and can induce the formation of
      ectopic heads when its mRNA is injected into Xenopus embryos [Bouwmeester, T.,
      Kim, S., Lu, B. & De Robertis, E. M. (1996) Nature (London) 382, 595-601]. Here
      we describe the existence of a cerberus-related gene, Cerr1, in the mouse. Cerr1
      encodes a putative secreted protein that is 48% identical to cerberus over a 110
      amino acid region. Analysis of a mouse interspecific backcross panel demonstrated
      that Cerr1 mapped to the central portion of mouse chromosome 4. In early gastrula
      stage mouse embryos, Cerr1 is expressed in the anterior visceral endoderm and in
      the anterior definitive endoderm. In somite stage embryos, Cerr1 expression is
      restricted to the most recently formed somites and in the anterior presomitic
      mesoderm. Germ layer explant recombination assays demonstrated that Cerr1
      expressing somitic-presomitic mesoderm, but not older Cerr1-nonexpressing somitic
      mesoderm, was able to mimic the anterior neuralizing ability of anterior
      mesendoderm and maintain Otx2 expression in competent ectoderm. In most Lim1-/-
      headless embryos, Cerr1 expression in the anterior endoderm was weak or absent.
      These results suggest that Cerr1 may play a role in anterior neural induction and
      somite formation during mouse development.

PMID- 9600943
TI  - A resource range invariance rule for optimal offspring size predicts patterns of
      variability in parental phenotypes.
AB  - Previous analysis of the rules regarding how much more a female should invest in
      a litter of size C rather than producing a litter with one more offspring
      revealed an invariance relationship between litter size and the range of
      resources per offspring in any litter size. The rule is that the range of
      resources per offspring should be inversely proportional to litter size. Here we
      present a modification of this rule that relates litter size to the total
      resources devoted to reproduction at that litter size. The result is that the
      range of resources devoted to reproduction should be the same for all litter
      sizes. When parental phenotypes covary linearly with resources devoted to
      reproduction, then those traits should also show equal ranges within each litter
      size category (except for litters of one). We tested this prediction by examining
      the range in body size (=total length) of female mosquito fish (Gambusia hubbsi)
      at different litter sizes. Because resources devoted to reproduction may take
      many forms (e.g., nest defense), this prediction may have broad applicability.

PMID- 9600944
TI  - Unexpected homology between inducible cell wall protein QID74 of filamentous
      fungi and BR3 salivary protein of the insect Chironomus.
AB  - A gene, qid74, of mycoparasitic filamentous fungus Trichoderma harzianum and its
      allies encodes a cell wall protein that is induced by replacing glucose in the
      culture medium with chitin (simulated mycoparasitism conditions). Because no
      trace of this gene can be detected in related species such as Gibberella
      fujikuroi and Saccharomyces cerevisiae, the qid74 gene appears to have arisen de
      novo within the genus Trichoderma. Qid74 protein, 687 residues long, is now seen
      as highly conserved tandem repeats of the 59-residue-long unit. This unit itself,
      however, may have arisen as tandem repeats of the shorter 13-residue-long basic
      unit. Within the genus Trichoderma, the amino acid sequence of Qid74 proteins has
      been conserved in toto. The most striking is the fact that Qid74 shares 25.3%
      sequence identity with the carboxyl-terminal half of the 1,572-residue-long BR3
      protein of the dipteran insect Chironomus tentans. BR3 protein is secreted by the
      salivary gland of each aquatic larva of Chironomus to form a tube to house
      itself. Furthermore, the consensus sequence derived from these 59-residue-long
      repeating units resembles those of epidermal growth factor-like domains found in
      divergent invertebrate and vertebrate proteins as to the positions of critical
      cysteine residues and homology of residues surrounding these cysteines.

PMID- 9600945
TI  - Male fitness increases when females are eliminated from gene pool: implications
      for the Y chromosome.
AB  - Because the two sexes share a common gene pool while performing many different
      biological functions, mutations benefiting one sex may not accumulate due to
      counter selection in the other sex. In these experiments 99% of a haploid genome
      of Drosophila melanogaster was constrained to segregate like a male-limited Y
      chromosome for 41 generations, thereby eliminating potential counter selection in
      females. The synthetic Y chromosomes rapidly accumulated genetic variation that
      increased male fitness and decreased female fitness. The survival and fertility
      of females declined when they were mated to males expressing the synthetic Y
      chromosomes. These results suggests that opposing selection between the sexes may
      substantially interfere with sex-specific adaptation. They also demonstrate how
      intersexual evolutionary conflict can lead to perpetual degeneration of the Y via
      genetic hitchhiking of deleterious mutations.

PMID- 9600946
TI  - Characterization of MADS homeotic genes in the fern Ceratopteris richardii.
AB  - The MADS genes encode a family of transcription factors, some of which control
      the identities of floral organs in flowering plants. To understand the role of
      MADS genes in the evolution of floral organs, five MADS genes (CMADS1, 2, 3, 4,
      and 6) were cloned from the fern Ceratopteris richardii, a nonflowering plant. A
      gene tree of partial amino acid sequences of seed plant and fern MADS genes
      showed that the fern genes form three subfamilies. All members of one of the fern
      MADS subfamilies have additional amino-terminal amino acids, which is a
      synapomorphic character of the AGAMOUS subfamily of the flowering plant MADS
      genes. Their structural similarity indicates a sister relationship between the
      two subfamilies. The temporal and spatial patterns of expression of the five fern
      MADS genes were assessed by Northern blot analyses and in situ hybridizations.
      CMADS1, 2, 3, and 4 are expressed similarly in the meristematic regions and
      primordia of sporophyte shoots and roots, as well as in reproductive structures,
      including sporophylls and sporangial initials, although the amount of expression
      in each tissue is different in each gene. CMADS6 is expressed in gametophytic
      tissues but not in sporophytic tissues. The lack of organ-specific expression of
      MADS genes in the reproductive structures of the fern sporophyte may indicate
      that the restriction of MADS gene expression to specific reproductive organs and
      the specialization of MADS gene functions as homeotic selector genes in the
      flowering plant lineage were important in floral organ evolution.

PMID- 9600947
TI  - A role for heterodimerization in nuclear localization of a homeodomain protein.
AB  - The A mating type genes of the mushroom Coprinus cinereus encode two families of
      dissimilar homeodomain proteins (HD1 and HD2). The proteins heterodimerize when
      mating cells fuse to generate a transcriptional regulator that promotes
      expression of genes required for early steps in sexual development. In previous
      work we showed that heterodimerization brings together different functional
      domains of the HD1 and HD2 proteins; a potential activation domain at the C
      terminus of the HD1 protein and an essential HD2 DNA-binding motif. Two predicted
      nuclear localization signals (NLS) are present in the HD1 protein but none are in
      the HD2 protein. We deleted each NLS separately from an HD1 protein and showed
      that one (NLS1) is essential for normal heterodimer function. Fusion of the NLS
      sequences to the C terminus of an HD2 protein compensated for their deletion from
      the HD1 protein partner and permitted the two modified proteins to form a
      functional transcriptional regulator. The nuclear targeting properties of the A
      protein NLS sequences were demonstrated by fusing the region that encodes them to
      the bacterial uidA (beta-glucuronidase) gene and showing that beta-glucuronidase
      expression localized to the nuclei of onion epidermal cells. These observations
      lead to the proposal that heterodimerization regulates entry of the active
      transcription factor complex to the nucleus.

PMID- 9600948
TI  - Silicatein alpha: cathepsin L-like protein in sponge biosilica.
AB  - Earth's biota produces vast quantities of polymerized silica at ambient
      temperatures and pressures by mechanisms that are not understood. Silica spicules
      constitute 75% of the dry weight of the sponge Tethya aurantia, making this
      organism uniquely tractable for analyses of the proteins intimately associated
      with the biosilica. Each spicule contains a central protein filament, shown by x
      ray diffraction to exhibit a highly regular, repeating structure. The protein
      filaments can be dissociated to yield three similar subunits, named silicatein
      alpha, beta, and gamma. The molecular weights and amino acid compositions of the
      three silicateins are similar, suggesting that they are members of a single
      protein family. The cDNA sequence of silicatein alpha, the most abundant of these
      subunits, reveals that this protein is highly similar to members of the cathepsin
      L and papain family of proteases. The cysteine at the active site in the
      proteases is replaced by serine in silicatein alpha, although the six cysteines
      that form disulfide bridges in the proteases are conserved. Silicatein alpha also
      contains unique tandem arrays of multiple hydroxyls. These structural features
      may help explain the mechanism of biosilicification and the recently discovered
      activity of the silicateins in promoting the condensation of silica and
      organically modified siloxane polymers (silicones) from the corresponding silicon
      alkoxides. They suggest the possibility of a dynamic role of the silicateins in
      silicification of the sponge spicule and offer the prospect of a new synthetic
      route to silica and siloxane polymers at low temperature and pressure and neutral
      pH.

PMID- 9600949
TI  - Genomic evidence for two functionally distinct gene classes.
AB  - Analyses of complete genomes indicate that a massive prokaryotic gene transfer
      (or transfers) preceded the formation of the eukaryotic cell. In comparisons of
      the entire set of Methanococcus jannaschii genes with their orthologs from
      Escherichia coli, Synechocystis 6803, and the yeast Saccharomyces cerevisiae, it
      is shown that prokaryotic genomes consist of two different groups of genes. The
      deeper, diverging informational lineage codes for genes which function in
      translation, transcription, and replication, and also includes GTPases, vacuolar
      ATPase homologs, and most tRNA synthetases. The more recently diverging
      operational lineage codes for amino acid synthesis, the biosynthesis of
      cofactors, the cell envelope, energy metabolism, intermediary metabolism, fatty
      acid and phospholipid biosynthesis, nucleotide biosynthesis, and regulatory
      functions. In eukaryotes, the informational genes are most closely related to
      those of Methanococcus, whereas the majority of operational genes are most
      closely related to those of Escherichia, but some are closest to Methanococcus or
      to Synechocystis.

PMID- 9600950
TI  - Glucose-regulated interaction of a regulatory subunit of protein phosphatase 1
      with the Snf1 protein kinase in Saccharomyces cerevisiae.
AB  - The Snf1 protein kinase family has been conserved in eukaryotes. In the yeast
      Saccharomyces cerevisiae, Snf1 is essential for transcription of glucose
      repressed genes in response to glucose starvation. The direct interaction between
      Snf1 and its activating subunit, Snf4, within the kinase complex is regulated by
      the glucose signal. Glucose inhibition of the Snf1-Snf4 interaction depends on
      protein phosphatase 1 and its targeting subunit, Reg1. Here we show that Reg1
      interacts with the Snf1 catalytic domain in the two-hybrid system. This
      interaction increases in response to glucose limitation and requires the
      conserved threonine in the activation loop of the kinase, a putative
      phosphorylation site. The inhibitory effect of Reg1 appears to require the Snf1
      regulatory domain because a reg1Delta mutation no longer relieves glucose
      repression of transcription when Snf1 function is provided by the isolated
      catalytic domain. Finally, we show that abolishing the Snf1 catalytic activity by
      mutation of the ATP-binding site causes elevated, constitutive interaction with
      Reg1, indicating that Snf1 negatively regulates its own interaction with Reg1. We
      propose a model in which protein phosphatase 1, targeted by Reg1, facilitates the
      conformational change of the kinase complex from its active state to the
      autoinhibited state.

PMID- 9600951
TI  - Stage specificity, dose response, and doubling dose for mouse minisatellite germ
      line mutation induced by acute radiation.
AB  - Germ-line mutation induction at mouse minisatellite loci by acute irradiation
      with x-rays was studied at premeiotic and postmeiotic stages of spermatogenesis.
      An elevated paternal mutation rate was found after irradiation of premeiotic
      spermatogonia and stem cells, whereas the frequency of minisatellite mutation
      after postmeiotic irradiation of spermatids was similar to that in control
      litters. In contrast, paternal irradiation did not affect the maternal mutation
      rate. A linear dose-response curve for paternal mutation induced at premeiotic
      stages was found, with a doubling dose of 0.33 Gy, a value close to those
      obtained in mice after acute spermatogonia irradiation using other systems for
      mutation detection. High frequencies of spontaneous and induced mutations at
      minisatellite loci allow mutation induction to be evaluated at low doses of
      exposure in very small population samples, which currently makes minisatellite
      DNA the most powerful tool for monitoring radiation-induced germ-line mutation.

PMID- 9600952
TI  - Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and
      behavioral abnormalities.
AB  - A mouse model for Down syndrome, Ts1Cje, has been developed. This model has made
      possible a step in the genetic dissection of the learning, behavioral, and
      neurological abnormalities associated with segmental trisomy for the region of
      mouse chromosome 16 homologous with the so-called "Down syndrome region" of human
      chromosome segment 21q22. Tests of learning in the Morris water maze and
      assessment of spontaneous locomotor activity reveal distinct learning and
      behavioral abnormalities, some of which are indicative of hippocampal
      dysfunction. The triplicated region in Ts1Cje, from Sod1 to Mx1, is smaller than
      that in Ts65Dn, another segmental trisomy 16 mouse, and the learning deficits in
      Ts1Cje are less severe than those in Ts65Dn. In addition, degeneration of basal
      forebrain cholinergic neurons, which was observed in Ts65Dn, was absent in
      Ts1Cje.

PMID- 9600953
TI  - Wheat grain hardness results from highly conserved mutations in the friabilin
      components puroindoline a and b.
AB  - "Soft" and "hard" are the two main market classes of wheat (Triticum aestivum L.)
      and are distinguished by expression of the Hardness gene. Friabilin, a marker
      protein for grain softness (Ha), consists of two proteins, puroindoline a and b
      (pinA and pinB, respectively). We previously demonstrated that a glycine to
      serine mutation in pinB is linked inseparably to grain hardness. Here, we report
      that the pinB serine mutation is present in 9 of 13 additional randomly selected
      hard wheats and in none of 10 soft wheats. The four exceptional hard wheats not
      containing the serine mutation in pinB express no pinA, the remaining component
      of the marker protein friabilin. The absence of pinA protein was linked
      inseparably to grain hardness among 44 near-isogenic lines created between the
      soft variety Heron and the hard variety Falcon. Both pinA and pinB apparently are
      required for the expression of grain softness. The absence of pinA protein and
      transcript and a glycine-to-serine mutation in pinB are two highly conserved
      mutations associated with grain hardness, and these friabilin genes are the
      suggested tightly linked components of the Hardness gene. A previously described
      grain hardness related gene termed "GSP-1" (grain softness protein) is not
      controlled by chromosome 5D and is apparently not involved in grain hardness. The
      association of grain hardness with mutations in both pinA or pinB indicates that
      these two proteins alone may function together to effect grain softness.
      Elucidation of the molecular basis for grain hardness opens the way to
      understanding and eventually manipulating this wheat endosperm property.

PMID- 9600954
TI  - CIITA stimulation of transcription factor binding to major histocompatibility
      complex class II and associated promoters in vivo.
AB  - CIITA is a master transactivator of the major histocompatibility complex class II
      genes, which are involved in antigen presentation. Defects in CIITA result in
      fatal immunodeficiencies. CIITA activation is also the control point for the
      induction of major histocompatibility complex class II and associated genes by
      interferon-gamma, but CIITA does not bind directly to DNA. Expression of CIITA in
      G3A cells, which lack endogenous CIITA, followed by in vivo genomic footprinting,
      now reveals that CIITA is required for the assembly of transcription factor
      complexes on the promoters of this gene family, including DRA, Ii, and DMB. CIITA
      dependent promoter assembly occurs in interferon-gamma-inducible cell types, but
      not in B lymphocytes. Dissection of the CIITA protein indicates that
      transactivation and promoter loading are inseparable and reveal a requirement for
      a GTP binding motif. These findings suggest that CIITA may be a new class of
      transactivator.

PMID- 9600955
TI  - Eotaxin is required for the baseline level of tissue eosinophils.
AB  - Eotaxin is an eosinophil-selective chemokine that is constitutively expressed in
      a variety of organs such as the intestine. Previous studies have demonstrated
      that the recruitment of eosinophils during inflammation is partially dependent on
      eotaxin, but the function of constitutive eotaxin during homeostasis has not been
      examined. To elucidate the biological role of this molecule, we now examine
      tissue levels of eosinophils in healthy states in wild-type and eotaxin-deficient
      mice. The lamina propria of the jejunum of wild-type mice is demonstrated to
      express eotaxin mRNA, but not mRNA for the related monocyte chemoattractant
      proteins. Wild-type mice contained readily detectable eosinophils in the lamina
      propria of the jejunum. In contrast, mice genetically deficient in eotaxin had a
      large selective reduction in the number of eosinophils residing in the jejunum.
      The reduction of tissue eosinophils was not limited to the jejunum, because a
      loss of thymic eosinophils was also observed in eotaxin-deficient mice. These
      studies demonstrate that eotaxin is a fundamental regulator of the physiological
      trafficking of eosinophils during healthy states. Because a variety of chemokines
      are constitutively expressed, their involvement in the baseline trafficking of
      leukocytes into nonhematopoietic tissue should now be considered.

PMID- 9600956
TI  - Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized
      with fusions of dendritic and carcinoma cells.
AB  - Immunological unresponsiveness established by the elimination or anergy of self
      reactive lymphocyte clones is of importance to immunization against tumor
      associated antigens. In this study, we have investigated induction of immunity
      against the human MUC1 carcinoma-associated antigen in MUC1 transgenic mice
      unresponsive to MUC1 antigen. Immunization of adult MUC1 transgenic mice with
      irradiated MUC1-positive tumor cells was unsuccessful in reversing
      unresponsiveness to MUC1. By contrast, fusions of dendritic cells with MUC1
      positive tumor cells induced cellular and humoral immunity against MUC1.
      Immunization with the dendritic cell fusions that express MUC1 resulted in the
      rejection of established metastases and no apparent autoimmunity against normal
      tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor
      associated antigen is reversible by immunization with heterokaryons of dendritic
      cells and MUC1-positive carcinoma cells.

PMID- 9600957
TI  - B7-CTLA4 interaction enhances both production of antitumor cytotoxic T
      lymphocytes and resistance to tumor challenge.
AB  - Expression of B7-family costimulatory molecules CD80 (B7-1) and CD86 (B7-2) on
      tumor cells enhances host immunity. However, the role of the two B7 receptors,
      CD28 and CTLA4 (CD152), on T cells in antitumor immune response has not been
      clearly elucidated. Based on the effects of anti-CD28 and anti-CTLA4 mAbs on T
      cell response, it was proposed that CD28-B7 interaction promotes antitumor
      immunity, whereas B7-CTLA4 interaction down-regulates it. A critical test for the
      hypothesis is whether selective engagement of CTLA4 receptors by their natural
      ligands CD80 and CD86 enhances or reduces antitumor immunity. Here we used tumors
      expressing wild-type and mutant CD80, as well as mice with targeted mutation of
      CD28, to address this issue. We report that in syngeneic wild-type mice, B7W
      (W88>A), a CD80 mutant that has lost binding to CD28 but retained binding to
      CTLA4, can enhance the induction of antitumor cytotoxic T lymphocytes (CTL); B7Y
      (Y201>A), which binds neither CD28 nor CTLA4, fails to do so. Consistent with
      these observations, B7W-transfected J558 plasmocytoma and EL4 thymoma grow
      significantly more slowly than those transfected with either vector alone or with
      B7Y. Optimal tumor rejection requires wild-type CD80. Moreover, expression of a
      high level of CD80 on thymoma EL4 cells conveys immunity in mice with a targeted
      mutation of CD28 gene. Taken together, our results demonstrate that B7-CTLA4
      interaction enhances production of antitumor CTL and resistance to tumor
      challenge and that optimal enhancement of antitumor immunity by CD80 requires its
      engagement of both CD28 and CTLA4.

PMID- 9600958
TI  - A cell surface receptor defined by a mAb mediates a unique type of cell death
      similar to oncosis.
AB  - Cell death is mediated by distinct pathways including apoptosis and oncosis in
      response to various death signals. To characterize molecules involved in cell
      death, a panel of mAbs was raised by immunizing mice with apoptotic cells. One of
      these antibodies, designated anti-Porimin (for pro-oncosis receptor inducing
      membrane injury), was found to directly induce a unique type of cell death in
      Jurkat cells. Anti-Porimin defines a 110-kDa cell surface receptor on Jurkat
      cells. Functionally, anti-Porimin alone rapidly mediates pore formation on the
      plasma membrane and induces cell death without participation of complement. Both
      the cellular expression and functional characteristics of the Porimin antigen
      indicate that it is distinct from the CD95 (Fas/Apo-1) and other cell receptors
      known to induce apoptosis. Anti-Porimin-mediated cell death was preceded by cell
      aggregation, formation of plasma membrane pores, and the appearance of membrane
      blebs. More important, these cells show neither DNA fragmentation nor apoptotic
      bodies, but display lethal damage of the cell membrane. Cell death by anti
      Porimin is distinct from complement-dependent cytolysis or complement-independent
      apoptosis but is similar to that described for oncosis, a form of cell death
      accompanied by the membrane damage followed by karyolysis. The induction of cell
      death by anti-Porimin may represent a unique cell surface receptor-mediated
      pathway of cell death in the human lymphoid system.

PMID- 9600959
TI  - Posttranscriptional regulation of urokinase plasminogen activator receptor
      messenger RNA levels by leukocyte integrin engagement.
AB  - As an adhesion receptor, the beta2 integrin lymphocyte function-associated
      antigen-1 (LFA-1) contributes a strong adhesive force to promote T lymphocyte
      recirculation and interaction with antigen-presenting cells. As a signaling
      molecule, LFA-1-mediates transmembrane signaling, which leads to the generation
      of second messengers and costimulation resulting in T cell activation. We
      recently have demonstrated that, in costimulatory fashion, LFA-1 activation
      promotes the induction of T cell membrane urokinase plasminogen activator
      receptor (uPAR) and that this induced uPAR is functional. To investigate the
      mechanism(s) of this induction, we used the RNA polymerase II inhibitor 5, 6
      dichloro-1-beta-D-ribobenzimidazole and determined that uPAR mRNA degradation is
      delayed by LFA-1 activation. Cloning of the wild-type, deleted and mutated 3'
      untranslated region of the uPAR cDNA into a serum-inducible rabbit beta-globin
      cDNA reporter construct revealed that the AU-rich elements and, in particular the
      nonameric UUAUUUAUU sequence, are crucial cis-acting elements in uPAR mRNA
      degradation. Experiments in which Jurkat T cells were transfected with reporter
      constructs demonstrated that LFA-1 engagement was able to stabilize the unstable
      reporter mRNA containing the uPAR 3'-untranslated region. Our study reveals a
      consequence of adhesion receptor-mediated signaling in T cells, which is
      potentially important in the regulation of T cell activation, including
      production of cytokines and expression of proto-oncogenes, many of which are
      controlled through 3' AU-rich elements.

PMID- 9600960
TI  - Visualizing the dynamics of T cell activation: intracellular adhesion molecule 1
      migrates rapidly to the T cell/B cell interface and acts to sustain calcium
      levels.
AB  - T cell recognition typically involves both the engagement of a specific T cell
      receptor with a peptide/major histocompatibility complex (MHC) and a number of
      accessory interactions. One of the most important interactions is between the
      integrin lymphocyte function-associated antigen 1 (LFA-1) on the T cell and
      intracellular adhesion molecule 1 (ICAM-1) on an antigen-presenting cell. By
      using fluorescence video microscopy and an ICAM-1 fused to a green fluorescent
      protein, we find that the elevation of intracellular calcium in the T cell that
      is characteristic of activation is followed almost immediately by the rapid
      accumulation of ICAM-1 on a B cell at a tight interface between the two cells.
      This increased density of ICAM-1 correlates with the sustained elevation of
      intracellular calcium in the T cell, known to be critical for activation. The use
      of peptide/MHC complexes and ICAM-1 on a supported lipid bilayer to stimulate T
      cells also indicates a major role for ICAM-1/LFA-1 in T cell activation but,
      surprisingly, not for adhesion, as even in the absence of ICAM-1 the
      morphological changes and adhesive characteristics of an activated T cell are
      seen in this system. We suggest that T cell antigen receptor-mediated recognition
      of a very small number of MHC/peptide complexes could trigger LFA-1/ICAM-1
      clustering and avidity regulation, thus amplifying and stabilizing the production
      of second messengers.

PMID- 9600961
TI  - HCC-2, a human chemokine: gene structure, expression pattern, and biological
      activity.
AB  - Cloning and sequencing of the upstream region of the gene of the CC chemokine HCC
      1 led to the discovery of an adjacent gene coding for a CC chemokine that was
      named "HCC-2." The two genes are separated by 12-kbp and reside in a head-to-tail
      orientation on chromosome 17. At variance with the genes for HCC-1 and other
      human CC chemokines, which have a three-exon-two-intron structure, the HCC-2 gene
      consists of four exons and three introns. Expression of HCC-2 and HCC-1 as
      studied by Northern analysis revealed, in addition to the regular, monocistronic
      mRNAs, a common, bicistronic transcript. In contrast to HCC-1, which is expressed
      constitutively in numerous human tissues, HCC-2 is expressed only in the gut and
      the liver. HCC-2 shares significant sequence homology with CKbeta8 and the murine
      chemokines C10, CCF18/MRP-2, and macrophage inflammatory protein 1gamma, which
      all contain six instead of four conserved cysteines. The two additional cysteines
      of HCC-2 form a third disulfide bond, which anchors the COOH-terminal domain to
      the core of the molecule. Highly purified recombinant HCC-2 was tested on
      neutrophils, eosinophils, monocytes, and lymphocytes and was found to exhibit
      marked functional similarities to macrophage inflammatory protein 1alpha. It is a
      potent chemoattractant and inducer of enzyme release in monocytes and a
      moderately active attractant for eosinophils. Desensitization studies indicate
      that HCC-2 acts mainly via CC chemokine receptor CCR1.

PMID- 9600962
TI  - Multiple modes of cellular activation and virus transmission in HIV infection: a
      role for chronically and latently infected cells in sustaining viral replication.
AB  - CD4(+) T cell activation, required for virus replication in these cells, occurs
      in local microenvironmental domains in transient bursts. Thus, although most HIV
      originates from short-lived virus-producing cells, it is unlikely that chronic
      infection is generally sustained in rapid continuous cycles of productive
      infection as has been proposed. Such continuity of productive infection cycles
      would depend on efficient long-range transmission of HIV from one set of domains
      to another, in turn requiring the maintenance of sufficiently high concentrations
      of cell-free virus across lymphoid tissues at all times. By contrast, long-lived
      cellular sources of HIV maintain the capacity to infect newly activated cells at
      close range despite the temporal and spatial discontinuities of activation
      events. Such proximal activation and transmission (PAT) involving chronically and
      latently infected cells may be responsible for sustained infection, particularly
      when viral loads are low. Once CD4 cells are productively infected through PAT,
      they can infect other activated cells in their immediate vicinity. Such events
      propagate locally but generally do not spread systemically, unlike in the acute
      phase of the infection, because of the early establishment of protective anergy.
      Importantly, antiretroviral drug treatment is likely to differentially impact
      long-range transmission and PAT.

PMID- 9600963
TI  - Murine Nkg2d and Cd94 are clustered within the natural killer complex and are
      expressed independently in natural killer cells.
AB  - Natural killer (NK) cells express C-type lectin-like receptors, encoded in the NK
      gene complex, that interact with major histocompatibility complex class I and
      either inhibit or activate functional activity. Human NK cells express
      heterodimers consisting of CD94 and NKG2 family molecules, whereas murine NK
      cells express homodimers belonging to the Ly-49 family. The corresponding
      orthologues for other species, however, have not been described. In this report,
      we used probes derived from the expressed sequence tag database to clone C57BL/6
      derived cDNAs homologous to human NKG2-D and CD94. Among normal tissues, murine
      NKG2-D and CD94 transcripts are highly expressed only in activated NK cells,
      including both Ly-49A+ and Ly-49A- subpopulations. Additionally, mNKG2-D is
      expressed in murine NK cell clones KY-1 and KY-2, whereas mCD94 expression is
      observed only in KY-1 cells but not KY-2. Last, we have finely mapped the
      physical location of the Cd94 (centromeric) and Nkg2d (telomeric) genes between
      Cd69 and the Ly49 cluster in the NK complex. Thus, these data indicate the
      expanding complexity of the NK complex and the corresponding repertoire of C-type
      lectin-like receptors on murine NK cells.

PMID- 9600964
TI  - Abolition of morphine-immunosuppression in mice lacking the mu-opioid receptor
      gene.
AB  - Opiates are potent analgesic and addictive compounds. They also act on immune
      responses, and morphine, the prototypic opiate, has been repeatedly described as
      an immunosuppressive drug. Pharmacological studies have suggested that the
      inhibitory action of opiates on immunity is mediated by multiple opioid receptor
      sites but molecular evidence has remained elusive. Recently, three genes encoding
      mu- (MOR), delta-, and kappa-opioid receptors have been cloned. To investigate
      whether the mu-opioid receptor is functionally implicated in morphine
      immunosuppression in vivo, we have examined immune responses of mice with a
      genetic disruption of the MOR gene. In the absence of drug, there was no
      difference between wild-type and mutant mice with regard to a large number of
      immunological endpoints, suggesting that the lack of MOR-encoded protein has
      little consequence on immune status. Chronic morphine administration induced
      lymphoid organ atrophy, diminished the ratio of CD4(+)CD8(+) cells in the thymus
      and strongly reduced natural killer activity in wild-type mice. None of these
      effects was observed in MOR-deficient mice after morphine treatment. This
      demonstrates that the MOR gene product represents a major molecular target for
      morphine action on the immune system. Because our previous studies of MOR
      deficient mice have shown that this receptor protein is also responsible for
      morphine analgesia, reward, and physical dependence, the present results imply
      that MOR-targeted therapeutic drugs that are developed for the treatment of pain
      or opiate addiction may concomitantly influence immune responses.

PMID- 9600966
TI  - Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant
      but not autosomal recessive distal renal tubular acidosis.
AB  - Primary distal renal tubular acidosis (dRTA) is characterized by reduced ability
      to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis,
      nephrocalcinosis, and nephrolithiasis. Kindreds showing either autosomal dominant
      or recessive transmission are described. Mutations in the chloride-bicarbonate
      exchanger AE1 have recently been reported in four autosomal dominant dRTA
      kindreds, three of these altering codon Arg589. We have screened 26 kindreds with
      primary dRTA for mutations in AE1. Inheritance was autosomal recessive in
      seventeen kindreds, autosomal dominant in one, and uncertain due to unknown
      parental phenotype or sporadic disease in eight kindreds. No mutations in AE1
      were detected in any of the autosomal recessive kindreds, and analysis of linkage
      showed no evidence of linkage of recessive dRTA to AE1. In contrast, heterozygous
      mutations in AE1 were identified in the one known dominant dRTA kindred, in one
      sporadic case, and one kindred with two affected brothers. In the dominant
      kindred, the mutation Arg-589/Ser cosegregated with dRTA in the extended
      pedigree. An Arg-589/His mutation in the sporadic case proved to be a de novo
      mutation. In the third kindred, affected brothers both have an intragenic 13-bp
      duplication resulting in deletion of the last 11 amino acids of AE1. These
      mutations were not detected in 80 alleles from unrelated normal individuals.
      These findings underscore the key role of Arg-589 and the C terminus in normal
      AE1 function, and indicate that while mutations in AE1 cause autosomal dominant
      dRTA, defects in this gene are not responsible for recessive disease.

PMID- 9600965
TI  - Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1alpha
      (SDF-1alpha) and SDF-1beta are abolished by CD26/dipeptidyl peptidase IV-mediated
      cleavage.
AB  - CD26 is a leukocyte-activation antigen that is expressed on T lymphocytes and
      macrophages and possesses dipeptidyl peptidase IV (DPPIV) activity, whose natural
      substrates have not been identified yet. CXC chemokines, stromal cell-derived
      factor 1alpha (SDF-1alpha) and 1beta (SDF-1beta), sharing the receptor CXCR-4,
      are highly efficacious chemoattractants for resting lymphocytes and CD34(+)
      progenitor cells, and they efficiently block the CXCR-4-mediated entry into cells
      of T cell line tropic strains of HIV type 1 (HIV-1). Here we show that both the
      chemotactic and antiviral activities of these chemokines are abrogated by DPPIV
      mediated specific removal of the N-terminal dipeptide, not only when the
      chemokines are produced in transformed mouse L cell line to express human CD26
      but also when they were exposed to a human T cell line (H9) physiologically
      expressing CD26. Mutagenesis of SDF-1alpha confirmed the critical requirement of
      the N-terminal dipeptide for its chemotactic and antiviral activities. These data
      suggest that CD26-mediated cleavage of SDF-1alpha and SDF-1beta likely occurs in
      human bodies and promotes HIV-1 replication and disease progression. They may
      also explain why memory function of CD4(+) cells is preferentially lost in HIV-1
      infection. Furthermore, CD26 would modulate various other biological processes in
      which SDF-1alpha and SDF-1beta are involved.

PMID- 9600967
TI  - A human fibrosarcoma inhibits systemic angiogenesis and the growth of
      experimental metastases via thrombospondin-1.
AB  - Concomitant tumor resistance refers to the ability of some large primary tumors
      to hold smaller tumors in check, preventing their progressive growth. Here, we
      demonstrate this phenomenon with a human tumor growing in a nude mouse and show
      that it is caused by secretion by the tumor of the inhibitor of angiogenesis,
      thrombospondin-1. When growing subcutaneously, the human fibrosarcoma line HT1080
      induced concomitant tumor resistance, preventing the growth of experimental
      B16/F10 melanoma metastases in the lung. Resistance was due to the production by
      the tumor cells themselves of high levels of thrombospondin-1, which was present
      at inhibitory levels in the plasma of tumor-bearing animals who become unable to
      mount an angiogenic response in their corneas. Animals carrying tumors formed by
      antisense-derived subclones of HT1080 that secreted low or no thrombospondin had
      weak or no ability to control the growth of lung metastases. Although purified
      human platelet thrombospondin-1 had no effect on the growth of melanoma cells in
      vitro, when injected into mice it was able to halt the growth of their
      experimental metastases, providing clear evidence of the efficacy of
      thrombospondin-1 as an anti-tumor agent.

PMID- 9600968
TI  - In vivo detection and imaging of phosphatidylserine expression during programmed
      cell death.
AB  - One of the earliest events in programmed cell death is the externalization of
      phosphatidylserine, a membrane phospholipid normally restricted to the inner
      leaflet of the lipid bilayer. Annexin V, an endogenous human protein with a high
      affinity for membrane bound phosphatidylserine, can be used in vitro to detect
      apoptosis before other well described morphologic or nuclear changes associated
      with programmed cell death. We tested the ability of exogenously administered
      radiolabeled annexin V to concentrate at sites of apoptotic cell death in vivo.
      After derivatization with hydrazinonicotinamide, annexin V was radiolabeled with
      technetium 99m. In vivo localization of technetium 99m hydrazinonicotinamide
      annexin V was tested in three models: fuminant hepatic apoptosis induced by anti
      Fas antibody injection in BALB/c mice; acute rejection in ACI rats with
      transplanted heterotopic PVG cardiac allografts; and cyclophosphamide treatment
      of transplanted 38C13 murine B cell lymphomas. External radionuclide imaging
      showed a two- to sixfold increase in the uptake of radiolabeled annexin V at
      sites of apoptosis in all three models. Immunohistochemical staining of cardiac
      allografts for exogenously administered annexin V revealed intense staining of
      numerous myocytes at the periphery of mononuclear infiltrates of which only a few
      demonstrated positive apoptotic nuclei by the terminal
      deoxynucleotidyltransferase-mediated UTP end labeling method. These results
      suggest that radiolabeled annexin V can be used in vivo as a noninvasive means to
      detect and serially image tissues and organs undergoing programmed cell death.

PMID- 9600969
TI  - CYR61, a product of a growth factor-inducible immediate early gene, promotes
      angiogenesis and tumor growth.
AB  - CYR61 is a secreted, cysteine-rich, heparin-binding protein encoded by a growth
      factor-inducible immediate-early gene. Acting as an extracellular, matrix
      associated signaling molecule, CYR61 promotes the adhesion of endothelial cells
      through interaction with the integrin alphaVbeta3 and augments growth factor
      induced DNA synthesis in the same cell type. In this study, we show that purified
      CYR61 stimulates directed migration of human microvascular endothelial cells in
      culture through an alphaV beta3-dependent pathway and induces neovascularization
      in rat corneas. Both the chemotactic and angiogenic activities of CYR61 can be
      blocked by specific anti-CYR61 antibodies. Whereas most human tumor-derived cell
      lines tested express CYR61, the gastric adenocarcinoma cell line RF-1 does not.
      Expression of the CYR61 cDNA under the regulation of a constitutive promoter in
      RF-1 cells significantly enhances the tumorigenicity of these cells as measured
      by growth in immunodeficient mice, resulting in tumors that are larger and more
      vascularized than those produced by control RF-1 cells. Taken together, these
      results identify CYR61 as an angiogenic inducer that can promote tumor growth and
      vascularization; the results also suggest potential roles for CYR61 in
      physiologic and pathologic neovascularization.

PMID- 9600970
TI  - Chaperone-facilitated copper binding is a property common to several classes of
      familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants.
AB  - Mutations in Cu, Zn superoxide dismutase (SOD1) cause the neurodegenerative
      disease familial amyotrophic lateral sclerosis from an as-yet-unidentified toxic
      property(ies). Analysis in Saccharomyces cerevisiae of a broad range of human
      familial amyotrophic lateral sclerosis-linked SOD1 mutants (A4V, G37R, G41D,
      H46R, H48Q, G85R, G93C, and I113T) reveals one property common to these mutants
      (including two at residues that coordinate the catalytic copper): Each does
      indeed bind copper and scavenge oxygen-free radicals in vivo. Neither decreased
      copper binding nor decreased superoxide scavenging activity is a property shared
      by all mutants. The demonstration that shows that all mutants tested do bind
      copper under physiologic conditions supports a mechanism of SOD1 mutant-mediated
      disease arising from aberrant copper-mediated chemistry catalyzed by less tightly
      folded (and hence less constrained) mutant enzymes. The mutant enzymes also are
      shown to acquire the catalytic copper in vivo through the action of CCS, a
      specific copper chaperone for SOD1, which in turn suggests that a search for
      inhibitors of this SOD1 copper chaperone may represent a therapeutic avenue.

PMID- 9600971
TI  - Angiostatin gene transfer: inhibition of tumor growth in vivo by blockage of
      endothelial cell proliferation associated with a mitosis arrest.
AB  - The antitumoral effects that follow the local delivery of the N-terminal fragment
      of human plasminogen (angiostatin K3) have been studied in two xenograft murine
      models. Angiostatin delivery was achieved by a defective adenovirus expressing a
      secretable angiostatin K3 molecule from the cytomegalovirus promoter (AdK3). In
      in vitro studies, AdK3 selectively inhibited endothelial cell proliferation and
      disrupted the G2/M transition induced by M-phase-promoting factors. AdK3-infected
      endothelial cells showed a marked mitosis arrest that correlated with the down
      regulation of the M-phase phosphoproteins. A single intratumoral injection of
      AdK3 into preestablished rat C6 glioma or human MDA-MB-231 breast carcinoma grown
      in athymic mice was followed by a significant arrest of tumor growth, which was
      associated with a suppression of neovascularization within and at the vicinity of
      the tumors. AdK3 therapy also induced a 10-fold increase in apoptotic tumor cells
      as compared with a control adenovirus. Furthermore, we showed that systemic
      injection of AdK3 delayed C6 tumor establishment and growth, confirming that
      angiostatin can function in a paracrin manner. Our data support the concept that
      targeted antiangiogenesis, using adenovirus-mediated gene transfer, represents a
      promising alternative strategy for delivering antiangiogenic factors as their
      bolus injections present unsolved pharmacological problems.

PMID- 9600972
TI  - Abnormal transport along the lysosomal pathway in mucolipidosis, type IV disease.
AB  - Mucolipidosis, type IV (ML-IV) is an autosomal recessive storage disease that is
      characterized by lysosomal accumulation of sphingolipids, phospholipids, and acid
      mucopolysaccharides. Unlike most other storage diseases, the lysosomal hydrolases
      participating in the catabolism of the stored molecules appear to be normal. In
      the present study, we examined the hypothesis that the ML-IV phenotype might
      arise from abnormal transport along the lysosomal pathway. By using various
      markers for endocytosis, we found that plasma membrane internalization and
      recycling were nearly identical in ML-IV and normal fibroblasts. A fluorescent
      analog of lactosylceramide (LacCer) was used to study plasma membrane lipid
      internalization and subsequent transport. Lipid internalization at 19 degreesC
      was similar in both cell types; however, 40-60 min after raising the temperature
      to 37 degreesC, the fluorescent lipid accumulated in the lysosomes of ML-IV cells
      but was mainly concentrated at the Golgi complex of normal fibroblasts.
      Biochemical studies demonstrated that at these time points, hydrolysis of the
      lipid analog was minimal ( approximately 7%) in both cell types. A fluorescence
      ratio imaging assay was developed to monitor accumulation of fluorescent LacCer
      in the lysosomes and showed that the apparent concentration of the lipid
      increased more rapidly and to a greater extent in ML-IV cells than in normal
      fibroblasts. By 60 min, LacCer apparently decreased in the lysosomes of normal
      fibroblasts but not in ML-IV cells, suggesting that lipid efflux from the
      lysosomes was also impaired. These results demonstrate that there is a defect in
      ML-IV fibroblasts that affects membrane sorting and/or late steps of endocytosis.

PMID- 9600973
TI  - Continuous amperometric monitoring of glucose in a brittle diabetic chimpanzee
      with a miniature subcutaneous electrode.
AB  - The performance of an amperometric biosensor, consisting of a subcutaneously
      implanted miniature (0.29 mm diameter, 5 x 10(-4) cm2 mass transporting area), 90
      s 10-90% rise/decay time glucose electrode, and an on-the-skin electrocardiogram
      Ag/AgCl electrode was tested in an unconstrained, naturally diabetic, brittle,
      type I, insulin-dependent chimpanzee. The chimpanzee was trained to wear on her
      wrist a small electronic package and to present her heel for capillary blood
      samples. In five sets of measurements, averaging 5 h each, 82 capillary blood
      samples were assayed, their concentrations ranging from 35 to 400 mg/dl. The
      current readings were translated to blood glucose concentration by assaying, at t
      = 1 h, one blood sample for each implanted sensor. The rms error in the
      correlation between the sensor-measured glucose concentration and that in
      capillary blood was 17.2%, 4.9% above the intrinsic 12.3% rms error of the Accu
      Chek II reference, through which the illness of the chimpanzee was routinely
      managed. Linear regression analysis of the data points taken at t>1 h yielded the
      relationship (Accu-Chek) = 0. 98 x (implanted sensor) + 4.2 mg/dl, r2 = 0.94. The
      capillary blood and the subcutaneous glucose concentrations were statistically
      indistinguishable when the rate of change was less than 1 mg/(dl. min). However,
      when the rate of decline exceeded 1.8 mg/(dl.min) after insulin injection, the
      subcutaneous glucose concentration was transiently higher.

PMID- 9600974
TI  - Identification of rat susceptibility loci for adjuvant-oil-induced arthritis.
AB  - One intradermal injection of incomplete Freund's adjuvant-oil induces a T cell
      mediated inflammatory joint disease in DA rats. Susceptibility genes for oil
      induced arthritis (OIA) are located both within and outside the major
      histocompatibility complex (MHC, Oia1). We have searched for disease-linked non
      MHC loci in an F2 intercross between DA rats and MHC-identical but arthritis
      resistant LEW.1AV1 rats. A genome-wide scan with microsatellite markers revealed
      two major chromosome regions that control disease incidence and severity: Oia2 on
      chromosome 4 (P = 4 x 10(-13)) and Oia3 on chromosome 10 (P = 1 x 10(-6)). All
      animals homozygous for DA alleles at both loci developed severe arthritis,
      whereas all those homozygous for LEW.1AV1 alleles were resistant. These results
      have general implications for situations where nonspecific activation of the
      immune system (e.g., incomplete Freund's adjuvant-oil) causes inflammation and
      disease, either alone or in conjunction with specific antigens. They may also
      provide clues to the etiology of inflammatory diseases in humans, including
      rheumatoid arthritis.

PMID- 9600975
TI  - Increased rates of CD4(+) and CD8(+) T lymphocyte turnover in simian
      immunodeficiency virus-infected macaques.
AB  - Defining the rate at which T cells turn over has important implications for our
      understanding of T lymphocyte homeostasis and AIDS pathogenesis, yet little
      information on T cell turnover is available. We used the nucleoside analogue
      bromodeoxyuridine (BrdUrd) in combination with five-color flow cytometric
      analysis to evaluate T lymphocyte turnover rates in normal and simian
      immunodeficiency virus (SIV)-infected rhesus macaques. T cells in normal animals
      turned over at relatively rapid rates, with memory cells turning over more
      quickly than naive cells. In SIV-infected animals, the labeling and elimination
      rates of both CD4(+) and CD8(+) BrdUrd-labeled cells were increased by 2- to 3
      fold as compared with normal controls. In normal and SIV-infected animals, the
      rates of CD4(+) T cell BrdUrd-labeling and decay were closely correlated with
      those of CD8(+) T cells. The elimination rate of BrdUrd-labeled cells was
      accelerated in both naive and memory T lymphocytes in SIV-infected animals. Our
      results provide direct evidence for increased rates of both CD4(+) and CD8(+) T
      cell turnover in AIDS virus infection and have important implications for our
      understanding of T cell homeostasis and the mechanisms responsible for CD4(+) T
      cell depletion in AIDS.

PMID- 9600976
TI  - Human sulfite oxidase R160Q: identification of the mutation in a sulfite oxidase
      deficient patient and expression and characterization of the mutant enzyme.
AB  - Sulfite oxidase catalyzes the terminal reaction in the degradation of sulfur
      amino acids. Genetic deficiency of sulfite oxidase results in neurological
      abnormalities and often leads to death at an early age. The mutation in the
      sulfite oxidase gene responsible for sulfite oxidase deficiency in a 5-year-old
      girl was identified by sequence analysis of cDNA obtained from fibroblast mRNA to
      be a guanine to adenine transition at nucleotide 479 resulting in the amino acid
      substitution of Arg-160 to Gln. Recombinant protein containing the R160Q mutation
      was expressed in Escherichia coli, purified, and characterized. The mutant
      protein contained its full complement of molybdenum and heme, but exhibited 2% of
      native activity under standard assay conditions. Absorption spectroscopy of the
      isolated molybdenum domains of native sulfite oxidase and of the R160Q mutant
      showed significant differences in the 480- and 350-nm absorption bands,
      suggestive of altered geometry at the molybdenum center. Kinetic analysis of the
      R160Q protein showed an increase in Km for sulfite combined with a decrease in
      kcat resulting in a decrease of nearly 1,000-fold in the apparent second-order
      rate constant kcat/Km. Kinetic parameters for the in vitro generated R160K mutant
      were found to be intermediate in value between those of the native protein and
      the R160Q mutant. Native sulfite oxidase was rapidly inactivated by
      phenylglyoxal, yielding a modified protein with kinetic parameters mimicking
      those of the R160Q mutant. It is proposed that Arg-160 attracts the anionic
      substrate sulfite to the binding site near the molybdenum.

PMID- 9600977
TI  - Ultraviolet radiation, but not gamma radiation or etoposide-induced DNA damage,
      results in the phosphorylation of the murine p53 protein at serine-389.
AB  - Polyclonal antibodies were produced and purified that selectively react with a
      p53 epitope containing the murine phosphoserine-389 or the human phosphoserine
      392 residue, but not the unphosphorylated epitope. These antibodies, termed alpha
      392, were employed to demonstrate that the phosphorylation of this serine-389
      residue in the p53 protein occurs in vivo in response to ultraviolet radiation of
      cells containing the p53 protein. After ultraviolet radiation of cells in
      culture, p53 levels increase and concomitantly serine-389 is phosphorylated in
      these cells. By contrast, the serine-389 phosphorylation of the p53 protein was
      not detected by these antibodies in the increased levels of p53 protein made in
      response to gamma radiation or the treatment of cells with etoposide. These
      results demonstrate an ultraviolet responsive and specific phosphorylation site
      at serine-389 of the mouse or serine-392 of the human p53 protein. Previous
      studies have demonstrated that this phosphorylation of p53 activates the protein
      for specific DNA binding. This study demonstrates in vivo a unique
      phosphorylation site in the p53 protein that responds to a specific type of DNA
      damage.

PMID- 9600978
TI  - Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine
      homolog.
AB  - A secreted CC chemokine homolog, encoded by the MC148 gene of molluscum
      contagiosum virus, potently interfered with the chemotaxis of human monocytes,
      lymphocytes, and neutrophils in response to a large number of CC and CXC
      chemokines with diverse receptor specificities. Evidence that the viral protein
      binds to human chemokine receptors was obtained by competition binding and
      calcium mobilization experiments. The broad spectrum chemokine antagonistic
      activity of MC148 can explain the prolonged absence of an inflammatory response
      in skin tumors that harbor replicating molluscum contagiosum virus.

PMID- 9600979
TI  - Lineage commitment in the progeny of murine hematopoietic preprogenitor cells:
      influence of thrombopoietin and interleukin 5.
AB  - Normal mouse marrow cells were stimulated by stem cell factor (SCF) to form
      dispersed or multicentric blast colonies containing progenitor cells committed to
      various hematopoietic lineages. Combination of the eosinophil-specific regulator
      interleukin 5 with SCF increased the frequency of colonies containing eosinophil
      committed progenitor cells with multicentric but not dispersed blast colonies.
      Combination of thrombopoietin with SCF increased the frequency of colonies
      containing megakaryocyte-committed progenitor cells with both types of blast
      colony. Neither interleukin 5 nor thrombopoietin significantly altered the number
      or total cell content of blast colonies or progenitor cell numbers in blast
      colonies from those stimulated by SCF alone. No correlation was observed between
      total progenitor cell content and the presence or absence of either eosinophil or
      megakaryocyte progenitors in either type of blast colony. The data argue against
      a random process as being responsible for the formation of particular committed
      progenitor cells or the possibility that lineage-specific regulators merely
      enhance survival of such committed progenitor cells formed in developing blast
      colonies.

PMID- 9600980
TI  - t(11;22)(q23;q11.2) In acute myeloid leukemia of infant twins fuses MLL with
      hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge
      and velocardiofacial syndromes.
AB  - We examined the MLL genomic translocation breakpoint in acute myeloid leukemia of
      infant twins. Southern blot analysis in both cases showed two identical MLL gene
      rearrangements indicating chromosomal translocation. The rearrangements were
      detectable in the second twin before signs of clinical disease and the intensity
      relative to the normal fragment indicated that the translocation was not
      constitutional. Fluorescence in situ hybridization with an MLL-specific probe and
      karyotype analyses suggested t(11;22)(q23;q11. 2) disrupting MLL. Known 5'
      sequence from MLL but unknown 3' sequence from chromosome band 22q11.2 formed the
      breakpoint junction on the der(11) chromosome. We used panhandle variant PCR to
      clone the translocation breakpoint. By ligating a single-stranded oligonucleotide
      that was homologous to known 5' MLL genomic sequence to the 5' ends of BamHI
      digested DNA through a bridging oligonucleotide, we formed the stem-loop template
      for panhandle variant PCR which yielded products of 3.9 kb. The MLL genomic
      breakpoint was in intron 7. The sequence of the partner DNA from band 22q11.2 was
      identical to the hCDCrel (human cell division cycle related) gene that maps to
      the region commonly deleted in DiGeorge and velocardiofacial syndromes. Both MLL
      and hCDCrel contained homologous CT, TTTGTG, and GAA sequences within a few base
      pairs of their respective breakpoints, which may have been important in uniting
      these two genes by translocation. Reverse transcriptase-PCR amplified an in-frame
      fusion of MLL exon 7 to hCDCrel exon 3, indicating that an MLL-hCDCrel chimeric
      mRNA had been transcribed. Panhandle variant PCR is a powerful strategy for
      cloning translocation breakpoints where the partner gene is undetermined. This
      application of the method identified a region of chromosome band 22q11.2 involved
      in both leukemia and a constitutional disorder.

PMID- 9600981
TI  - Molecular characterization of the phenylacetic acid catabolic pathway in
      Pseudomonas putida U: the phenylacetyl-CoA catabolon.
AB  - Fourteen different genes included in a DNA fragment of 18 kb are involved in the
      aerobic degradation of phenylacetic acid by Pseudomonas putida U. This catabolic
      pathway appears to be organized in three contiguous operons that contain the
      following functional units: (i) a transport system, (ii) a phenylacetic acid
      activating enzyme, (iii) a ring-hydroxylation complex, (iv) a ring-opening
      protein, (v) a beta-oxidation-like system, and (vi) two regulatory genes. This
      pathway constitutes the common part (core) of a complex functional unit
      (catabolon) integrated by several routes that catalyze the transformation of
      structurally related molecules into a common intermediate (phenylacetyl-CoA).

PMID- 9600982
TI  - A double-stranded RNA element from a hypovirulent strain of Rhizoctonia solani
      occurs in DNA form and is genetically related to the pentafunctional AROM protein
      of the shikimate pathway.
AB  - M2 is a double-stranded RNA (dsRNA) element occurring in the hypovirulent isolate
      Rhs 1A1 of the plant pathogenic basidiomycete Rhizoctonia solani. Rhs 1A1
      originated as a sector of the virulent field isolate Rhs 1AP, which contains no
      detectable amount of the M2 dsRNA. The complete sequence (3,570 bp) of the M2
      dsRNA has been determined. A 6.9-kbp segment of total DNA from either Rhs 1A1 or
      Rhs 1AP hybridizes with an M2-specific cDNA probe. The sequences of M2 dsRNA and
      of PCR products generated from Rhs 1A1 total DNA were found to be identical. Thus
      this report describes a fungal host containing full-length DNA copies of a dsRNA
      element. A major portion of the M2 dsRNA is located in the cytoplasm, whereas a
      smaller amount is found in mitochondria. Based on either the universal or the
      mitochondrial genetic code of filamentous fungi, one strand of M2 encodes a
      putative protein of 754 amino acids. The resulting polypeptide has all four
      motifs of a dsRNA viral RNA-dependent RNA polymerase (RDRP) and is
      phylogenetically related to the RDRP of a mitochondrial dsRNA associated with
      hypovirulence in strain NB631 of Cryphonectria parasitica, incitant of chestnut
      blight. This polypeptide also has significant sequence similarity with two
      domains of a pentafunctional polypeptide, which catalyzes the five central steps
      of the shikimate pathway in yeast and filamentous fungi.

PMID- 9600983
TI  - Regulation of the pAD1 sex pheromone response of Enterococcus faecalis by direct
      interaction between the cAD1 peptide mating signal and the negatively regulating,
      DNA-binding TraA protein.
AB  - The Enterococcus faecalis conjugative plasmid pAD1 (60 kb) encodes a mating
      response to the recipient-produced peptide sex pheromone cAD1. The response
      involves two key plasmid-encoded regulatory proteins: TraE1, which positively
      regulates all or most structural genes relating to conjugation, and TraA, which
      binds DNA and negatively regulates expression of traE1. In vitro studies that
      included development of a DNA-associated protein-tag affinity chromatography
      technique showed that TraA (37.9 kDa) binds directly to cAD1 near its carboxyl
      terminal end and, as a consequence, loses its affinity for DNA. Analyses of
      genetically modified TraA proteins indicated that truncations within the carboxyl
      terminal 9 residues significantly affected the specificity of peptide-directed
      association/dissociation of DNA. The data support earlier observations that
      transposon insertions near the 3' end of traA eliminated the ability of cells to
      respond to cAD1.

PMID- 9600984
TI  - Electrostatic interactions between rotor and stator in the bacterial flagellar
      motor.
AB  - Bacterial flagellar motors rotate, obtaining power from the membrane gradient of
      protons or, in some species, sodium ions. Torque generation in the flagellar
      motor must involve interactions between components of the rotor and components of
      the stator. Sites of interaction between the rotor and stator have not been
      identified. Mutational studies of the rotor protein FliG and the stator protein
      MotA showed that both proteins contain charged residues essential for motor
      rotation. This suggests that functionally important electrostatic interactions
      might occur between the rotor and stator. To test this proposal, we examined
      double mutants with charged-residue substitutions in both the rotor protein FliG
      and the stator protein MotA. Several combinations of FliG mutations with MotA
      mutations exhibited strong synergism, whereas others showed strong suppression,
      in a pattern that indicates that the functionally important charged residues of
      FliG interact with those of MotA. These results identify a functionally important
      site of interaction between the rotor and stator and suggest a hypothesis for
      electrostatic interactions at the rotor-stator interface.

PMID- 9600985
TI  - Restriction-modification gene complexes as selfish gene entities: roles of a
      regulatory system in their establishment, maintenance, and apoptotic mutual
      exclusion.
AB  - We have reported some type II restriction-modification (RM) gene complexes on
      plasmids resist displacement by an incompatible plasmid through postsegregational
      host killing. Such selfish behavior may have contributed to the spread and
      maintenance of RM systems. Here we analyze the role of regulatory genes (C),
      often found linked to RM gene complexes, in their interaction with the host and
      the other RM gene complexes. We identified the C gene of EcoRV as a positive
      regulator of restriction. A C mutation eliminated postsegregational killing by
      EcoRV. The C system has been proposed to allow establishment of RM systems in new
      hosts by delaying the appearance of restriction activity. Consistent with this
      proposal, bacteria preexpressing ecoRVC were transformed at a reduced efficiency
      by plasmids carrying the EcoRV RM gene complex. Cells carrying the BamHI RM gene
      complex were transformed at a reduced efficiency by a plasmid carrying a PvuII RM
      gene complex, which shares the same C specificity. The reduction most likely was
      caused by chromosome cleavage at unmodified PvuII sites by prematurely expressed
      PvuII restriction enzyme. Therefore, association of the C genes of the same
      specificity with RM gene complexes of different sequence specificities can confer
      on a resident RM gene complex the capacity to abort establishment of a second,
      incoming RM gene complex. This phenomenon, termed "apoptotic mutual exclusion,"
      is reminiscent of suicidal defense against virus infection programmed by other
      selfish elements. pvuIIC and bamHIC genes define one incompatibility group of
      exclusion whereas ecoRVC gene defines another.

PMID- 9600986
TI  - Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central
      nervous system neurotoxins.
AB  - Abeta1-42 is a self-associating peptide whose neurotoxic derivatives are thought
      to play a role in Alzheimer's pathogenesis. Neurotoxicity of amyloid beta protein
      (Abeta) has been attributed to its fibrillar forms, but experiments presented
      here characterize neurotoxins that assemble when fibril formation is inhibited.
      These neurotoxins comprise small diffusible Abeta oligomers (referred to as
      ADDLs, for Abeta-derived diffusible ligands), which were found to kill mature
      neurons in organotypic central nervous system cultures at nanomolar
      concentrations. At cell surfaces, ADDLs bound to trypsin-sensitive sites and
      surface-derived tryptic peptides blocked binding and afforded neuroprotection.
      Germ-line knockout of Fyn, a protein tyrosine kinase linked to apoptosis and
      elevated in Alzheimer's disease, also was neuroprotective. Remarkably,
      neurological dysfunction evoked by ADDLs occurred well in advance of cellular
      degeneration. Without lag, and despite retention of evoked action potentials,
      ADDLs inhibited hippocampal long-term potentiation, indicating an immediate
      impact on signal transduction. We hypothesize that impaired synaptic plasticity
      and associated memory dysfunction during early stage Alzheimer's disease and
      severe cellular degeneration and dementia during end stage could be caused by the
      biphasic impact of Abeta-derived diffusible ligands acting upon particular neural
      signal transduction pathways.

PMID- 9600987
TI  - Cerebral cortical hyperactivation in response to mental stress in patients with
      coronary artery disease.
AB  - The central nervous system (CNS) effects of mental stress in patients with
      coronary artery disease (CAD) are unexplored. The present study used positron
      emission tomography (PET) to measure brain correlates of mental stress induced by
      an arithmetic serial subtraction task in CAD and healthy subjects. Mental stress
      resulted in hyperactivation in CAD patients compared with healthy subjects in
      several brain areas including the left parietal cortex [angular gyrus/parallel
      sulcus (area 39)], left anterior cingulate (area 32), right visual association
      cortex (area 18), left fusiform gyrus, and cerebellum. These same regions were
      activated within the CAD patient group during mental stress versus control
      conditions. In the group of healthy subjects, activation was significant only in
      the left inferior frontal gyrus during mental stress compared with counting
      control. Decreases in blood flow also were produced by mental stress in CAD
      versus healthy subjects in right thalamus (lateral dorsal, lateral posterior),
      right superior frontal gyrus (areas 32, 24, and 10), and right middle temporal
      gyrus (area 21) (in the region of the auditory association cortex). Of particular
      interest, a subgroup of CAD patients that developed painless myocardial ischemia
      during mental stress had hyperactivation in the left hippocampus and inferior
      parietal lobule (area 40), left middle (area 10) and superior frontal gyrus (area
      8), temporal pole, and visual association cortex (area 18), and a concomitant
      decrease in activation observed in the anterior cingulate bilaterally, right
      middle and superior frontal gyri, and right visual association cortex (area 18)
      compared with CAD patients without myocardial ischemia. These findings
      demonstrate an exaggerated cerebral cortical response and exaggerated asymmetry
      to mental stress in individuals with CAD.

PMID- 9600988
TI  - Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal
      neurons.
AB  - The amyloid precursor protein (APP) plays a crucial role in the pathogenesis of
      Alzheimer's disease. During intracellular transport APP undergoes a series of
      proteolytic cleavages that lead to the release either of an amyloidogenic
      fragment called beta-amyloid (Abeta) or of a nonamyloidogenic secreted form
      consisting of the ectodomain of APP (APPsec). It is Abeta that accumulates in the
      brain lesions that are thought to cause the disease. By reducing the cellular
      cholesterol level of living hippocampal neurons by 70% with lovastatin and methyl
      beta-cyclodextrin, we show that the formation of Abeta is completely inhibited
      while the generation of APPsec is unperturbed. This inhibition of Abeta formation
      is accompanied by increased solubility in the detergent Triton X-100 and is fully
      reversible by the readdition of cholesterol to previously depleted cells. Our
      results show that cholesterol is required for Abeta formation to occur and imply
      a link between cholesterol, Abeta, and Alzheimer's disease.

PMID- 9600989
TI  - How do owls localize interaurally phase-ambiguous signals?
AB  - Owls and other animals, including humans, use the difference in arrival time of
      sounds between the ears to determine the direction of a sound source in the
      horizontal plane. When an interaural time difference (ITD) is conveyed by a
      narrowband signal such as a tone, human beings may fail to derive the direction
      represented by that ITD. This is because they cannot distinguish the true ITD
      contained in the signal from its phase equivalents that are ITD +/- nT, where T
      is the period of the stimulus tone and n is an integer. This uncertainty is
      called phase-ambiguity. All ITD-sensitive neurons in birds and mammals respond to
      an ITD and its phase equivalents when the ITD is contained in narrowband signals.
      It is not known, however, if these animals show phase-ambiguity in the
      localization of narrowband signals. The present work shows that barn owls (Tyto
      alba) experience phase-ambiguity in the localization of tones delivered by
      earphones. We used sound-induced head-turning responses to measure the sound
      source directions perceived by two owls. In both owls, head-turning angles varied
      as a sinusoidal function of ITD. One owl always pointed to the direction
      represented by the smaller of the two ITDs, whereas a second owl always chose the
      direction represented by the larger ITD (i.e., ITD - T).

PMID- 9600990
TI  - alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease
      and dementia with lewy bodies.
AB  - Lewy bodies and Lewy neurites are the defining neuropathological characteristics
      of Parkinson's disease and dementia with Lewy bodies. They are made of abnormal
      filamentous assemblies of unknown composition. We show here that Lewy bodies and
      Lewy neurites from Parkinson's disease and dementia with Lewy bodies are stained
      strongly by antibodies directed against amino-terminal and carboxyl-terminal
      sequences of alpha-synuclein, showing the presence of full-length or close to
      full-length alpha-synuclein. The number of alpha-synuclein-stained structures
      exceeded that immunoreactive for ubiquitin, which is currently the most sensitive
      marker of Lewy bodies and Lewy neurites. Staining for alpha-synuclein thus will
      replace staining for ubiquitin as the preferred method for detecting Lewy bodies
      and Lewy neurites. We have isolated Lewy body filaments by a method used for the
      extraction of paired helical filaments from Alzheimer's disease brain. By
      immunoelectron microscopy, extracted filaments were labeled strongly by anti
      alpha-synuclein antibodies. The morphologies of the 5- to 10-nm filaments and
      their staining characteristics suggest that extended alpha-synuclein molecules
      run parallel to the filament axis and that the filaments are polar structures.
      These findings indicate that alpha-synuclein forms the major filamentous
      component of Lewy bodies and Lewy neurites.

PMID- 9600991
TI  - The effect of recombinant recoverin on the photoresponse of truncated rod
      photoreceptors.
AB  - Recoverin is a heterogeneously acylated calcium-binding protein thought to
      regulate visual transduction. Its effect on the photoresponse was investigated by
      dialyzing the recombinant protein into truncated salamander rod outer segments.
      At high Ca2+ (Ca), myristoylated recoverin (Ca-recoverin) prolonged the recovery
      phase of the bright flash response but had less effect on the dim flash response.
      The prolongation of recovery had an apparent Kd for Ca of 13 microM and a Hill
      coefficient of 2. The prolongation was shown to be mediated by inhibition of
      rhodopsin deactivation. After a sudden imposed drop in Ca concentration, the
      effect of recoverin switched off with little lag. The myristoyl (C14:0)
      modification of recoverin increased its activity 12-fold, and the C12:0 or C14:2
      acyl group gave similar effects. These experiments support the notion that
      recoverin mediates Ca-dependent inhibition of rhodopsin phosphorylation and
      thereby controls light-triggered phosphodiesterase activity, particularly at high
      light levels.

PMID- 9600992
TI  - Altered brain neurotransmitter receptors in transgenic mice expressing a portion
      of an abnormal human huntington disease gene.
AB  - Loss of neurotransmitter receptors, especially glutamate and dopamine receptors,
      is one of the pathologic hallmarks of brains of patients with Huntington disease
      (HD). Transgenic mice that express exon 1 of an abnormal human HD gene (line
      R6/2) develop neurologic symptoms at 9-11 weeks of age through an unknown
      mechanism. Analysis of glutamate receptors (GluRs) in symptomatic 12-week-old
      R6/2 mice revealed decreases compared with age-matched littermate controls in the
      type 1 metabotropic GluR (mGluR1), mGluR2, mGluR3, but not the mGluR5 subtype of
      G protein-linked mGluR, as determined by [3H]glutamate receptor binding, protein
      immunoblotting, and in situ hybridization. Ionotropic alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid and kainate receptors were also decreased, while
      N-methyl-D-aspartic acid receptors were not different compared with controls.
      Other neurotransmitter receptors known to be affected in HD were also decreased
      in R6/2 mice, including dopamine and muscarinic cholinergic, but not gamma
      aminobutyric acid receptors. D1-like and D2-like dopamine receptor binding was
      drastically reduced to one-third of control in the brains of 8- and 12-week-old
      R6/2 mice. In situ hybridization indicated that mGluR and D1 dopamine receptor
      mRNA were altered as early as 4 weeks of age, long prior to the onset of clinical
      symptoms. Thus, altered expression of neurotransmitter receptors precedes
      clinical symptoms in R6/2 mice and may contribute to subsequent pathology.

PMID- 9600993
TI  - Preferential localization of self-stimulation sites in striosomes/patches in the
      rat striatum.
AB  - Histological sections of the mammalian striatum reveal a "matrix" that is
      histochemically distinguishable from patches, or "striosomes". The latter are
      cross sections of a compartment that consists primarily of tube-shaped structures
      radiating through the matrix. As a test of the hypothesis that the function of
      the striosome/patch compartment includes the mediation of behaviors related to
      reward, the present study examined electrical self-stimulation of the
      caudoputamen in rats with electrodes in either of the two compartments. Rats
      acquired and maintained bar-pressing responses that were contingent on
      stimulation through electrodes making contact with striosomes/patches more
      reliably than animals with electrodes terminating exclusively in the matrix. The
      results provide in vivo evidence that the striosome/patch compartment is
      functionally differentiated from the matrix compartment: Stimulation centered in
      or around the striosome/patch compartment but not in the matrix led to rapid
      acquisition of a new behavior.

PMID- 9600994
TI  - Heterogeneity of subcellular localization and electrophoretic mobility of
      survival motor neuron (SMN) protein in mammalian neural cells and tissues.
AB  - Spinal muscular atrophy is caused by defects in the survival motor neuron (SMN)
      gene. To better understand the patterns of expression of SMN in neuronal cells
      and tissues, we raised a polyclonal antibody (abSMN) against a synthetic
      oligopeptide from SMN exon 2. AbSMN immunostaining in neuroblastoma cells and
      mouse and human central nervous system (CNS) showed intense labeling of nuclear
      "gems," along with prominent nucleolar immunoreactivity in mouse and human CNS
      tissues. Strong cytoplasmic labeling was observed in the perikarya and proximal
      dendrites of human spinal motor neurons but not in their axons. Immunoblot
      analysis revealed a 34-kDa species in the insoluble protein fractions from human
      SY5Y neuroblastoma cells, embryonic mouse spinal cord cultures, and human CNS
      tissue. By contrast, a 38-kDa species was detected in the cytosolic fraction of
      SY5Y cells. We conclude that SMN protein is expressed prominently in both the
      cytoplasm and nucleus in multiple types of neurons in brain and spinal cord, a
      finding consistent with a role for SMN as a determinant of neuronal viability.

PMID- 9600995
TI  - Temporal dynamics of verbal object comprehension.
AB  - Knowledge of the stage composition and the temporal dynamics of human cognitive
      operations is critical for building theories of higher mental activity. This
      information has been difficult to acquire, even with different combinations of
      techniques such as refined behavioral testing, electrical recording/interference,
      and metabolic imaging studies. Verbal object comprehension was studied herein in
      a single individual, by using three tasks (object naming, auditory word
      comprehension, and visual word comprehension), two languages (English and Farsi),
      and four techniques (stimulus manipulation, direct cortical electrical
      interference, electrocorticography, and a variation of the technique of direct
      cortical electrical interference to produce time-delimited effects, called
      timeslicing), in a subject in whom indwelling subdural electrode arrays had been
      placed for clinical purposes. Electrical interference at a pair of electrodes on
      the left lateral occipitotemporal gyrus interfered with naming in both languages
      and with comprehension in the language tested (English). The naming and
      comprehension deficit resulted from interference with processing of verbal object
      meaning. Electrocorticography indices of cortical activation at this site during
      naming started 250-300 msec after visual stimulus presentation. By using the
      timeslicing technique, which varies the onset of electrical interference relative
      to the behavioral task, we found that completion of processing for verbal object
      meaning varied from 450 to 750 msec after current onset. This variability was
      found to be a function of the subject's familiarity with the objects.

PMID- 9600996
TI  - Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff:
      evidence for an alcohol receptor?
AB  - Alcohols in the homologous series of n-alcohols increase in central nervous
      system depressant potency with increasing chain length until a "cutoff" is
      reached, after which further increases in molecular size no longer increase
      alcohol potency. A similar phenomenon has been observed in the regulation of
      ligand-gated ion channels by alcohols. Different ligand-gated ion channels
      exhibit radically different cutoff points, suggesting the existence of discrete
      alcohol binding pockets of variable size on these membrane proteins. The
      identification of amino acid residues that determine the alcohol cutoff may,
      therefore, provide information about the location of alcohol binding sites.
      Alcohol regulation of the glycine receptor is critically dependent on specific
      amino acid residues in transmembrane domains 2 and 3 of the alpha subunit. We now
      demonstrate that these residues in the glycine alpha1 and the gamma-aminobutyric
      acid rho1 receptors also control alcohol cutoff. By mutation of Ser-267 to Gln,
      it was possible to decrease the cutoff in the glycine alpha1 receptor, whereas
      mutation of Ile-307 and/or Trp-328 in the gamma-aminobutyric acid rho1 receptor
      to smaller residues increased the cutoff. These results support the existence of
      alcohol binding pockets in these membrane proteins and suggest that the amino
      acid residues present at these positions can control the size of the alcohol
      binding cavity.

PMID- 9600997
TI  - Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with
      targeted disruption of endothelial nitric oxide synthase.
AB  - Cardiac myocytes have been shown to express constitutively endothelial nitric
      oxide synthase (eNOS) (nitric oxide synthase 3), the activation of which has been
      implicated in the regulation of myocyte L-type voltage-sensitive calcium channel
      current (ICa-L) and myocyte contractile responsiveness to parasympathetic nervous
      system signaling, although this implication remains controversial. Therefore, we
      examined the effect of the muscarinic cholinergic agonist carbachol (CCh) on ICa
      L and contractile amplitude in isoproterenol (ISO)-prestimulated ventricular
      myocytes isolated from adult mice, designated eNOSnull mice, with targeted
      disruption of the eNOS gene. Although both eNOSnull and wild-type (WT)
      ventricular myocytes exhibited similar increases in ICa-L in response to ISO,
      there was no measurable suppression of ICa-L by CCh in cells from eNOSnull mice,
      in contrast to cells from WT mice. These results were reflected in the absence of
      an effect of CCh on the positive inotropic effect of ISO in eNOSnull myocytes.
      Also, unlike myocytes from WT animals, eNOSnull myocytes failed to exhibit an
      increase in cGMP content in response to CCh. Nevertheless, the pharmacologic
      nitric oxide donors 3-morpholino-sydnonimine and S-nitroso-acetyl-cystein
      increased cGMP generation and suppressed ISO-augmented ICa-L in eNOSnull cells,
      suggesting that the signal transduction pathway(s) downstream of eNOS remained
      intact. Of importance, activation of the acetylcholine-activated K+ channel by
      CCh was unaffected in atrial and ventricular eNOSnull myocytes. These results
      confirm the obligatory role of eNOS in coupling muscarinic receptor activation to
      cGMP-dependent control of ICa-L in cardiac myocytes.

PMID- 9600998
TI  - Does the colonic H,K-ATPase also act as an Na,K-ATPase?
AB  - We previously have demonstrated that the colonic P-ATPase alpha subunit cDNA
      encodes an H,K-ATPase when expressed in Xenopus laevis oocytes. Besides its high
      level of amino acid homology (75%) with the Na,K-ATPase, the colonic H,K-ATPase
      also shares a common pharmacological profile with Na,K-ATPase, because both are
      ouabain-sensitive and Sch 28080-insensitive. These features raise the possibility
      that an unrecognized property of the colonic H, K-ATPase would be Na+
      translocation. To test this hypothesis, ion-selective microelectrodes were used
      to measure the intracellular Na+ activity of X. laevis oocytes expressing various
      combinations of P-ATPase subunits. The results show that expression in oocytes of
      the colonic H,K-ATPase affects intracellular Na+ homeostasis in a way similar to
      the expression of the Bufo marinus Na,K-ATPase; intracellular Na+ activity is
      lower in oocytes expressing the colonic H,K-ATPase or the B. marinus Na,K-ATPase
      than in oocytes expressing the gastric H,K-ATPase or a beta subunit alone. In
      oocytes expressing the colonic H,K-ATPase, the decrease in intracellular Na+
      activity persists when diffusive Na+ influx is enhanced by functional expression
      of the amiloride-sensitive epithelial Na+ channel, suggesting that the decrease
      is related to increased active Na+ efflux. The Na+ decrease depends on the
      presence of K+ in the external medium and is inhibited by 2 mM ouabain, a
      concentration that inhibits the colonic H,K-ATPase. These data are consistent
      with the hypothesis that the colonic H,K-ATPase may transport Na+, acting as an
      (Na,H),K-ATPase. Despite its molecular and functional characterization, the
      physiological role of the colonic (Na,H),K-ATPase in colonic and renal ion
      homeostasis remains to be elucidated.

PMID- 9600999
TI  - The gamma subunit of the Na,K-ATPase induces cation channel activity.
AB  - The gamma subunit of the Na,K-ATPase is a hydrophobic protein of approximately 10
      kDa. The gamma subunit was expressed in Sf-9 insect cells and Xenopus oocytes to
      ascertain its role in Na,K-ATPase function. Immunoblotting has shown that the
      gamma subunit is expressed in Sf-9 cells infected with recombinant baculovirus
      containing the cDNA for the human gamma subunit. Confocal microscopy demonstrates
      that the gamma subunit can be delivered to the plasma membrane of Sf-9 cells
      independently of the other Na,K-ATPase subunits and that gamma colocalizes with
      alpha1 when these proteins are coexpressed. When Sf-9 cells were coinfected with
      alpha1 and gamma, antibodies to the gamma subunit were able to
      coimmunoprecipitate the alpha1 subunit, suggesting that gamma is able to
      associate with alpha1. The gamma subunit is a member of a family of single-pass
      transmembrane proteins that induces ion fluxes in Xenopus oocytes. Evidence that
      the gamma subunit is a functional component was supported by experiments showing
      gamma-induced cation channel activity when expressed in oocytes and increases in
      Na+ and K+ uptake when expressed in Sf-9 cells.

PMID- 9601000
TI  - Water does not flow across the tight junctions of MDCK cell epithelium.
AB  - Although it has been known for decades that the tight junctions of fluid
      transporting epithelia are leaky to ions, it has not been possible to determine
      directly whether significant transjunctional water movement also occurs. An
      optical microscopic technique was developed for the direct visualization of the
      flow velocity profiles within the lateral intercellular spaces of a fluid
      absorptive, cultured renal epithelium (MDCK) and used to determine the velocity
      of the fluid flow across the tight junction. The flow velocity within the lateral
      intercellular spaces fell to near zero adjacent to the tight junction, showing
      that significant transjunctional flow did not occur, even when transepithelial
      fluid movement was augmented by imposition of osmotic gradients.

PMID- 9601001
TI  - Generation of broad-spectrum disease resistance by overexpression of an essential
      regulatory gene in systemic acquired resistance.
AB  - The recently cloned NPR1 gene of Arabidopsis thaliana is a key regulator of
      acquired resistance responses. Upon induction, NPR1 expression is elevated and
      the NPR1 protein is activated, in turn inducing expression of a battery of
      downstream pathogenesis-related genes. In this study, we found that NPR1 confers
      resistance to the pathogens Pseudomonas syringae and Peronospora parasitica in a
      dosage-dependent fashion. Overexpression of NPR1 leads to enhanced resistance
      with no obvious detrimental effect on the plants. Thus, for the first time, a
      single gene is shown to be a workable target for genetic engineering of
      nonspecific resistance in plants.

PMID- 9601002
TI  - NEEDLY, a Pinus radiata ortholog of FLORICAULA/LEAFY genes, expressed in both
      reproductive and vegetative meristems.
AB  - The LEAFY/FLORICAULA genes from Arabidopsis and Antirrhinum are necessary for
      normal flower development and play a key role in diverse angiosperm species. A
      homologue of these flower meristem-identity genes, NEEDLY (NLY), has been
      identified in Pinus radiata. Although the NLY protein shares extensive sequence
      similarity with its angiosperm counterparts, it is lacking the proline-rich and
      acidic motifs thought to function as transcriptional activation domains. NLY
      already is expressed during vegetative development at least 5 years before the
      transition to the reproductive phase. Expression of NLY in transgenic Arabidopsis
      promotes floral fate, demonstrating that, despite its sequence divergence, NLY
      encodes a functional ortholog of the FLORICAULA/LEAFY genes of angiosperms.
      Expression of the LFY::NLY transgene can largely complement the defects in flower
      development caused by a severe lfy allele.

PMID- 9601003
TI  - The 3' untranslated region of a rice alpha-amylase gene functions as a sugar
      dependent mRNA stability determinant.
AB  - In plants, sugar feedback regulation provides a mechanism for control of
      carbohydrate allocation and utilization among tissues and organs. The sugar
      repression of alpha-amylase gene expression in rice provides an ideal model for
      studying the mechanism of sugar feedback regulation. We have shown previously
      that sugar repression of alpha-amylase gene expression in rice suspension cells
      involves control of both transcription rate and mRNA stability. The alpha-amylase
      mRNA is significantly more stable in sucrose-starved cells than in sucrose
      provided cells. To elucidate the mechanism of sugar-dependent mRNA turnover, we
      have examined the effect of alphaAmy3 3' untranslated region (UTR) on mRNA
      stability by functional analyses in transformed rice suspension cells. We found
      that the entire alphaAmy3 3' UTR and two of its subdomains can independently
      mediate sugar-dependent repression of reporter mRNA accumulation. Analysis of
      reporter mRNA half-lives demonstrated that the entire alphaAmy3 3' UTR and the
      two subdomains each functioned as a sugar-dependent destabilizing determinant in
      the turnover of mRNA. Nuclear run-on transcription analysis further confirmed
      that the alphaAmy3 3' UTR and the two subdomains did not affect the transcription
      rate of promoter. The identification of sequence elements in the alpha-amylase
      mRNA that dictate the differential stability has very important implications for
      the study of sugar-dependent mRNA decay mechanisms.

PMID- 9601005
TI  - The incompatible interaction between Phytophthora parasitica var. nicotianae race
      0 and tobacco is suppressed in transgenic plants expressing antisense
      lipoxygenase sequences.
AB  - Nicotiana tabacum 46-8 cultivar displays an incompatible interaction with race 0
      of Phytophthora parasitica var. nicotianae (Ppn), a fungal pathogen of most
      tobacco cultivars. At the plant level, incompatibility is characterized by the
      induction of lipoxygenase (LOX, EC = 1.13.11.12) activity and localized
      hypersensitive cell death before defense gene activation. To evaluate the
      involvement of LOX in the onset of plant defense, tobacco 46-8 plants were
      genetically engineered using full-length or partial-length antisense (AS) tobacco
      LOX cDNA constructs. AS expression strongly reduced elicitor- and pathogen
      induced LOX activity. Eight independent AS-LOX lines were selected and assayed
      for their response to Ppn. After root or stem inoculation with race 0, all AS-LOX
      lines but one displayed a compatible phenotype whereas control transformed
      plants, not containing the AS-LOX cassette, showed the typical incompatible
      reaction. The presence of the fungus in transgenic lines was demonstrated by PCR
      amplification of a Ppn-specific genomic sequence. A linear relationship was found
      between the extent of LOX suppression and the size of the lesion caused by the
      fungus. The AS-LOX plants also showed enhanced susceptibility toward the
      compatible fungus Rhizoctonia solani. The results demonstrate the strong
      involvement of LOX in the establishment of incompatibility in plant-microorganism
      interactions, consistent with its role in the defense of host plants.

PMID- 9601004
TI  - A transient outward-rectifying K+ channel current down-regulated by cytosolic
      Ca2+ in Arabidopsis thaliana guard cells.
AB  - Sustained (noninactivating) outward-rectifying K+ channel currents have been
      identified in a variety of plant cell types and species. Here, in Arabidopsis
      thaliana guard cells, in addition to these sustained K+ currents, an inactivating
      outward-rectifying K+ current was characterized (plant A-type current: IAP). IAP
      activated rapidly with a time constant of 165 ms and inactivated slowly with a
      time constant of 7.2 sec at +40 mV. IAP was enhanced by increasing the duration
      (from 0 to 20 sec) and degree (from +20 to -100 mV) of prepulse
      hyperpolarization. Ionic substitution and relaxation (tail) current recordings
      showed that outward IAP was mainly carried by K+ ions. In contrast to the
      sustained outward-rectifying K+ currents, cytosolic alkaline pH was found to
      inhibit IAP and extracellular K+ was required for IAP activity. Furthermore,
      increasing cytosolic free Ca2+ in the physiological range strongly inhibited IAP
      activity with a half inhibitory concentration of approximately 94 nM. We present
      a detailed characterization of an inactivating K+ current in a higher plant cell.
      Regulation of IAP by diverse factors including membrane potential, cytosolic Ca2+
      and pH, and extracellular K+ and Ca2+ implies that the inactivating IAP described
      here may have important functions during transient depolarizations found in guard
      cells, and in integrated signal transduction processes during stomatal movements.

PMID- 9601006
TI  - Precisely full length, circularizable, complementary RNA: an infectious form of
      potato spindle tuber viroid.
AB  - The replication of many viral and subviral pathogens as well as the amplification
      of certain cellular genes proceeds via a rolling circle mechanism. For potato
      spindle tuber (PSTVd) and related viroids, the possible role of a circular (
      )strand RNA as a template for synthesis of (+)strand progeny is unclear. Infected
      plants appear to contain only multimeric linear (-)strand RNAs, and attempts to
      initiate infection with multimeric (-)PSTVd RNAs generally have failed. To
      examine critically the infectivity of monomeric (-)strand viroid RNAs, we have
      developed a ribozyme-based expression system for the production of precisely full
      length (-)strand RNAs whose termini are capable of undergoing facile
      circularization in vitro. Mechanical inoculation of tomato seedlings with
      electrophoretically purified (-)PSTVd RNA led to a small fraction of plants
      becoming infected whereas parallel assays with an analogous tomato planta macho
      viroid (-)RNA resulted in a much larger fraction of infected plants. Ribozyme
      mediated production of (-)PSTVd RNA in transgenic plants led to the appearance of
      monomeric circular (-)PSTVd RNA and large amounts of (+)PSTVd progeny. No
      monomeric circular (-)PSTVd RNA could be detected in naturally infected plants by
      using either ribonuclease protection or electrophoresis under partially
      denaturing conditions. Although not a component of the normal replicative
      pathway, precisely full length (-)PSTVd RNA appears to contain all of the
      structural and regulatory elements necessary for initiation of viroid
      replication.

PMID- 9601007
TI  - Anomalies in coral reef community metabolism and their potential importance in
      the reef CO2 source-sink debate.
AB  - It is not certain whether coral reefs are sources of or sinks for atmospheric
      CO2. Air-sea exchange of CO2 over reefs has been measured directly and inferred
      from changes in the seawater carbonate equilibrium. Such measurements have
      provided conflicting results. We provide community metabolic data that indicate
      that large changes in CO2 concentration can occur in coral reef waters via
      biogeochemical processes not directly associated with photosynthesis,
      respiration, calcification, and CaCO3 dissolution. These processes can
      significantly distort estimates of reef calcification and net productivity and
      obscure the contribution of coral reefs to global air-sea exchange of CO2. They
      may, nonetheless, explain apparent anomalies in the metabolic performance of
      reefs close to land and reconcile the differing experimental findings that have
      given rise to the CO2 debate.

PMID- 9601008
TI  - Epigenetics. Introduction.

PMID- 9601009
TI  - Gene silencing by methyl-CpG-binding proteins.
AB  - An important consequence of CpG methylation is the local silencing of gene
      expression. In part this can be mediated by direct interference of methylation
      with the binding of transcription factors. The major component of silencing,
      however, appears to be the binding of repressors that have an affinity for methyl
      CpG. We have studied two proteins that bind to methylated DNA, methyl-CpG-binding
      protein 1 (MeCP1) and MeCP2. MeCP2 is a relatively abundant chromosomal protein
      whose localization in the nucleus is primarily dependent on CpG methylation. We
      find that MeCP2 is a potent transcriptional repressor with a genome-wide
      distribution. MeCP1 requires multiple methylated CpGs for binding and has
      previously been implicated as a methyl-CpG-dependent transcriptional repressor.
      Recent cloning of a candidate gene for a component of MeCP1 may provide clues to
      its mechanism of action.

PMID- 9601010
TI  - DNA methylation, nucleosomes and the inheritance of chromatin structure and
      function.
AB  - The replication of the genome during S phase is a crucial period for the
      establishment and maintenance of programmes of differential gene activity.
      Existing chromosomal structures are disrupted during replication and reassembled
      on both daughter chromatids. The capacity to reassemble a particular chromatin
      structure with defined functional properties reflects the commitment of a cell
      type to a particular state of determination. The core and linker histones and
      their modifications, enzymes that modify the histones, DNA methylation and
      proteins that recognize methylated DNA within chromatin may all play independent
      or interrelated roles in defining the functional properties of chromatin. Pre
      existing protein-DNA interactions and DNA methylation in a parental chromosome
      will influence the structure and function of daughter chromosomes generating an
      epigenetic imprint. In this chapter we consider the events occurring at the
      eukaryotic replication fork, their consequences for pre-existing chromosomal
      structures and how an epigenetic imprint might be maintained.

PMID- 9601011
TI  - Heritable chromatin states induced by the Polycomb and trithorax group genes.
AB  - In Drosophila the Polycomb group (PcG) and trithorax group (trxG) genes are
      required to maintain differential expression patterns of many important
      developmental regulatory genes. The PcG is responsible for heritable silencing
      throughout development. At target genes PcG response elements (PREs) attract PcG
      protein complexes and induce the formation of higher-order chromatin structures.
      We have mapped the distribution of Polycomb and other PcG members at various
      target genes by using an improved formaldehyde cross-linking and chromatin
      immunoprecipitation technique. We find that Polycomb spreads locally from PREs
      over several kilobases, thereby probably stabilizing the silencing complexes.
      Members of the trxG co-localize at PREs. GAGA factor was found to be
      constitutively bound to PREs independently of gene activity. PREs associated with
      active genes appear to have increased amounts of bound GAGA. We have developed a
      system capable of switching a PRE between the on/off modes. PREs and trxG
      regulated elements are common chromosomal elements through which the proteins of
      the PcG/trxG exert their maintenance function on adjacent chromatin structures.

PMID- 9601012
TI  - The dynamics of globin gene expression and position effects.
AB  - We have used gene competition to study the regulation of the human beta-globin
      locus in transgenic mice as a model system of a multigene locus. The locus is
      regulated by the locus control region (LCR), which is required for the expression
      of all the genes. Analysis of the locus at the single-cell level shows that the
      LCR appears to interact directly with the genes via a looping mechanism. This
      interaction is monogenic, and the level of transcription is determined by the
      frequency and stability of LCR/gene complex formation. These parameters are
      dependent both on the distance between the LCR and gene(s), and the concentration
      of transcription factors in the nucleus. Disturbance of complex formation leads
      to position effects, particularly when the locus is integrated in a
      heterochromatic environment.

PMID- 9601013
TI  - Multiple epigenetic events regulate mating-type switching of fission yeast.
AB  - Two epigenetic events at mat1, one of which is DNA strand specific, are required
      to initiate recombination during mating-type switching. The third, a
      chromosomally borne imprinted event at the mat2/3 interval regulates silencing
      and directionality of switching, and prohibits interchromosomal recombination. We
      speculate that the unit of inheritance in the mat2/3 interval is both DNA plus
      its associated chromatin structure. Such a control is likely to be essential in
      maintaining particular states of gene expression during development.

PMID- 9601014
TI  - Nuclear organization and silencing: trafficking of Sir proteins.
AB  - In budding yeast genes integrated near telomeres succumb to a variegated pattern
      of gene repression that requires the silent information regulatory proteins
      Sir2p, Sir3p and Sir4p, which form a nucleosome-binding complex.
      Immunolocalization shows that the Sir proteins co-localize with the telomeric
      repeat binding protein Rap1p and with telomeric DNA in a limited number of foci
      near the periphery of interphase nuclei. All conditions tested so far that
      disrupt telomere proximal repression result in a dispersed staining pattern for
      Sir2p, Sir3p and Sir4p. Although the focal organization is clearly not sufficient
      for establishing repression, genetic studies suggest that the high local
      concentration of Sir proteins at telomeric foci facilitates the formation of
      repressed chromatin. In addition to its telomeric localization, Sir2p is shown by
      immunostaining and cross-linking to bind a subdomain of the nucleolus. In strains
      lacking an intact Sir4p, Sir3p also becomes concentrated in the nucleolus by a
      pathway requiring SIR2 and UTH4. This unexpected localization correlates with
      observed effects of sir mutations on rDNA stability and longevity, defining a new
      site of action for silent information regulatory factors. We report a novel WD40
      repeat-containing factor, Sif2p, that binds specifically to the Sir4p N-terminus.
      Like Sir1p and Uth4p, Sif2p antagonizes telomeric silencing by regulating an
      equilibrium between alternative assembly pathways at different subnuclear loci.

PMID- 9601015
TI  - Epigenetic mechanisms in the regulation of the maize Suppressor-mutator
      transposon.
AB  - Transcription and transposition of the maize Suppressor-mutator (Spm) transposon
      are epigenetically controlled. Methylation of specific element sequences prevents
      transcription and transposition in a heritable manner. Reactivation and
      demethylation occur in the presence of an active element, implying the existence
      of an element-encoded epigenetic activator. The methylation target sequences are
      the 0.2 kb promoter and an 0.35 kb GC-rich downstream sequence. Two Spm-encoded
      proteins, TnpA and TnpD, participate in transposition. In addition, TnpA has
      positive and negative regulatory activities. TnpA represses and activates the
      unmethylated and methylated Spm promoters, respectively, and it participates in
      the transient and heritable demethylation of the promoter and GC-rich region.
      There is evidence that TnpA-mediated repressor and epigenetic activator functions
      occur by different molecular mechanisms.

PMID- 9601016
TI  - Transgene-promoted epigenetic switches of chalcone synthase activity in petunia
      plants.
AB  - Epigenetic variation affecting pigment pattern formation in petunia flowers due
      to the insertion of transgenes encoding chalcone synthase is described. The loss
      of pigment formation in petals or parts of petals is due to the post
      transcriptional degradation of chalcone synthase RNA, from both the endogenous
      petunia chalcone synthase genes and from the chalcone synthase transgenes. The
      RNA cleavage pathway and its control are described. Different epigenetic states
      of RNA breakdown are correlated with specific cytosine methylation changes in the
      coding sequences of the genes. The probability, extent and developmental location
      of chalcone synthase RNA breakdown are related to the number and organization of
      transgenes in the genome but epigenetic switches that affect RNA turnover
      probably occur in meristems and between sexual generations. Hypotheses to explain
      how the transgenes influence the levels of chalcone synthase RNA breakdown and
      how different epigenetic states are created are discussed.

PMID- 9601017
TI  - Gene silencing in plants: relevance for genome evolution and the acquisition of
      genomic methylation patterns.
AB  - Transgenes often become silenced in plants because of repressive influences
      exerted by flanking plant DNA and/or because of interactions among multiple
      copies of closely linked transgenes. Repeated transgenes on different chromosomes
      can also interact in a way that leads to silencing and methylation, suggesting a
      previously unrecognized ability of unlinked homologous sequences to cross-talk in
      complex genomes. Non-Mendelian inheritance is a frequent consequence of these
      interactions because the silenced genes do not fully reactivate or lose
      methylation after segregating in progeny. Several examples of gene silencing in
      plants appear to reflect the action of genome defence system that methylates and
      inactivates foreign or invasive sequences such as transgenes and transposable
      elements. Because certain types of transposable elements are embedded in
      regulatory regions of plant genes and have become greatly amplified in plant
      genomes, they could contribute substantially to normal gene expression and to the
      generation of genomic methylation patterns. Polyploidy, which has been a major
      force in plant and vertebrate evolution, might encourage proliferation of
      transposable elements because genes in polyploids are duplicated and hence less
      susceptible to the consequences of insertional mutagenesis. Accordingly, the
      appearance of genome-wide methylation has often coincided with episodes of
      polyploidization.

PMID- 9601018
TI  - The host defence function of genomic methylation patterns.
AB  - It has long been held that reversible promoter methylation allows genes to be
      expressed in the appropriate cell types during development. However, no
      endogenous gene has been proven to be regulated in this way, and it does not
      appear that significant numbers of promoters are methylated in non-expressing
      tissues. It has recently become clear that the large majority of genomic 5
      methylcytosine is actually in parasitic sequence elements (transposons and
      endogenous retroviruses), and the primary function of DNA methylation now appears
      to be defence against the large burden of parasitic sequence elements, which
      constitute more than 35% of the human genome. Direct transcriptional repression
      provides short-term control, and the tendency of 5-methylcytosine to deaminate to
      thymidine drives irreversible inactivation. It is suggested that intragenomic
      parasites are recognized by virtue of their high copy number, and that the
      disturbances of methylation patterns commonly seen in human cancer cells activate
      a host of parasitic sequence elements, which destabilize the genome and tip the
      cell towards the transformed state.

PMID- 9601019
TI  - Mammalian X chromosome inactivation.
AB  - X chromosome inactivation in mammals requires expression of the gene Xist, which
      maps to the X chromosome inactivation centre (Xic) and encodes an untranslated
      RNA. Truncation of Xist RNA by gene targeting is lethal for female embryos and
      prevents the inactivation of the X chromosome carrying the deletion. This
      indicates that Xist RNA is necessary for initiation and propagation of the
      inactivation process. Xist is transcribed from the inactive X and its expression
      is silenced by DNA methylation, suggesting that methylation is crucial for
      shielding the active X chromosome against the inactivation process. Gene transfer
      experiments using transgenes the size of yeast artificial chromosomes have
      determined that a 450 kb fragment of DNA carrying Xist acts as an inactivation
      centre and is sufficient for initiation, propagation and maintenance of the
      inactive state. The elements for counting and choosing X chromosomes are part of
      the transgene. We have shown that X inactivation is mediated by a post
      translational mechanism, i.e. the stabilization of Xist RNA, rather than by the
      regulation of the Xist promoter.

PMID- 9601020
TI  - Methylation dynamics, epigenetic fidelity and X chromosome structure.
AB  - DNA methylation of the X chromosome is reviewed and discussed, with emphasis on
      the partial methylation seen in the mouse X-linked Pgk1 promoter region. A new
      study of partial methylation is presented in which the methylation of CpG site H3
      in the mouse Igf2 upstream region was quantitatively measured during growth of
      subcloned cells in tissue culture. Before subcloning the average methylation
      level was 50%. After subcloning, methylation was highly variable in early stage
      clones. With continued passage, clones initially having high methylation lost
      methylation, whereas clones initially having low methylation gained methylation.
      By about the 25th generation, all clones had returned to a steady-state
      methylation level of 50%. These findings are discussed in the context of
      epigenetic mechanisms and epigenetic fidelity. Interpretation of the results is
      made according to a model that assumes stochastic methylation and demethylation,
      with rate parameters influenced by local chromatin structure. A second type of
      study is reported in which we have measured chromatin accessibility differences
      between the active X chromosome (Xa) and the inactive X chromosome (Xi). We found
      that Xa/Xi differences in accessibility to DNase I are surprisingly labile.
      Relatively infrequent DNA nicks rapidly eliminate differential accessibility.

PMID- 9601021
TI  - Imprinting and gene silencing in mice and Drosophila.
AB  - H19 and Igf2 are located within a large imprinting domain that confers
      monoallelic silencing of parental alleles. The silent paternal allele of H19 is
      hypermethylated and relatively resistant to nucleases. Using a 130 kb yeast
      artificial chromosome clone, appropriate imprinting of both H19 and Igf2 was
      observed at single insert loci in transgenic mice. Imprinting was also observed
      for H19-lacZ transgenes containing 4 kb of upstream sequence, but only at
      multicopy loci. The H19 RNA is therefore not essential for imprinting. When the
      H19-lacZ transgene was introduced into Drosophila, a 1.2 kb region was identified
      within the 4 kb upstream flank that functioned as a bi-directional silencer. This
      cis element is located within a region that is apparently necessary for
      imprinting in mice. These studies suggest an evolutionarily conserved mechanism
      for gene silencing in Drosophila and imprinting in mice. We propose a new model
      for imprinting of H19 and Igf2 in mice in which silencing of H19 is the default
      state, and activation of the maternal allele requires a specific activator
      element.

PMID- 9601022
TI  - Making sense of imprinting the mouse and human IGF2R loci.
AB  - The mouse and human IGF2R genes are similar in terms of expression pattern, gene
      structure and organization. Both genes have features that are common to imprinted
      genes. These common features are allele-specific methylation and replication
      asynchrony, plus the ability to restrict expression to one parental allele in
      diploid cells despite the presence of two functional parental alleles. In inbred
      laboratory mice Igf2r is initially expressed from both parental chromosomes in
      preimplantation embryos, it then shows maternal-specific monoallelic expression
      in all tissues of the postimplantation embryo and adult. The human gene is
      similarly monoallelically expressed in preterm postimplantation embryonic tissues
      (preimplantation embryos have not been examined). The behaviour of the human gene
      then diverges from that observed in inbred mice because it shows biallelic
      expression in term embryonic tissues and in the adult. An extra difference
      displayed by the human gene is that monoallelic expression is polymorphic and
      only occurs in 50% of individuals. The mechanism of IGF2R imprinting will be
      discussed with relevance to these similarities and differences between the mouse
      and human genes.

PMID- 9601023
TI  - Imprinted genes in the Prader-Willi deletion.
AB  - Parent-of-origin-specific deletions of proximal chromosome 15q cause either the
      Prader-Willi syndrome (paternal deletion) or the Angelman syndrome (maternal
      deletion), two distinct neurodevelopmental disorders. In contrast to the Angelman
      syndrome, which can also be caused by mutations in a single gene (UBE3A, encoding
      a ubiquitin ligase), the Prader-Willi syndrome is caused by deletions in about
      two-thirds of cases and by maternal uniparental disomy in the remaining third.
      The consequence of both mechanisms, in addition to rare microdeletions or so
      called 'imprinting mutations', is lack of the products of multiple genes in the
      region that are normally expressed only from the paternal chromosome. One gene
      that is consistently silent in the Prader-Willi syndrome is SNRPN, which encodes
      the small nuclear ribonucleoprotein particle-associated polypeptide N that forms
      part of the spliceosomes in the brain. A systematic search for other imprinted
      genes in the Prader-Willi syndrome region revealed a paternally expressed
      transcript (IPW, for imprinted in the Prader-Willi region) and a similarly
      imprinted mouse homologue (Ipw) in the conserved syntenic region on mouse
      chromosome 7. Ipw is highly expressed in the brain and alternatively spliced to
      generate different transcripts. Since there is no open reading frame that is
      conserved in the human and mouse IPW genes, they are postulated to function as
      untranslated RNAs, possibly regulating transcription in cis in the region.

PMID- 9601024
TI  - Energetic roles of hydrogen bonds at the ureido oxygen binding pocket in the
      streptavidin-biotin complex.
AB  - The high-affinity streptavidin-biotin complex is characterized by an extensive
      hydrogen-bonding network. A study of hydrogen-bonding energetics at the ureido
      oxygen of biotin has been conducted with site-directed mutations at Asn 23, Ser
      27, and Tyr 43. A new competitive biotin binding assay was developed to provide
      direct equilibrium measurements of the alterations in Kd. S27A, Y43F, Y43A, N23A,
      and N23E mutants display DeltaDeltaG degrees at 37 degrees C relative to wild
      type streptavidin of 2.9, 1.2, 2.6, 3.5, and 2.6 kcal/mol, respectively. The
      equilibrium-binding enthalpies for all of the mutants were measured by isothermal
      titration calorimetry, and the Y43A and N23A mutants display large decreases in
      the equilibrium binding enthalpy at 25 degrees C of 8.9 and 6.9 kcal/mol,
      respectively. The S27A and N23E mutants displayed small decreases in binding
      enthalpy of 1.6 and 0.9 kcal/mol relative to wild-type, while the Y43F mutant
      displayed a -2.6 kcal/mol increase in the binding enthalpy at 25 degrees C. At 37
      degrees C, the Y43A and N23A mutants display decreases of 7.8 and 7.9 kcal/mol,
      respectively, while the S27A, N23E, and Y43F mutants displayed decreases of 4.9,
      3.7, and 1.2 kcal/mol relative to wild-type. Kinetic analyses were also conducted
      to probe the contributions of the hydrogen bonds to the activation barrier. Wild
      type streptavidin at 37 degrees C displays a koff of (4.1 +/- 0.3) x 10(-5) s-1,
      and the conservative Y43F, S27A, and N23A mutants displayed increases in koff to
      (20 +/- 1) x 10(-5) s-1, (660 +/- 40) x 10(-5) s-1, and (1030 +/- 220) x 10(-)5 s
      1, respectively. The Y43A and N23E mutants displayed 93-fold and 188-fold
      increases in koff, respectively. Activation energies and enthalpies for each of
      the mutants were determined by transition-state analysis of the dissociation rate
      temperature dependence. All of the mutants except Y43F display large reductions
      in the activation enthalpy. The Y43F mutant has a more positive activation
      enthalpy, and thus a more favorable activation entropy that underlies the overall
      reduction in the activation barrier. For the most conservative mutant at each
      ureido oxygen hydrogen-bonding position, bound-state alterations account for most
      of the energetic changes in a single transition-state model, suggesting that the
      ureido oxygen hydrogen-bonding interactions are broken in the dissociation
      transition state.

PMID- 9601025
TI  - Pre-steady state kinetic analysis of an enzymatic reaction monitored by time
      resolved electrospray ionization mass spectrometry.
AB  - For the first time, the new technique of time-resolved electrospray ionization
      mass spectrometry (ESI-MS) has been used to accurately measure the pre-steady
      state kinetics of an enzymatic reaction by monitoring a transient enzyme
      intermediate. The enzyme used to illustrate this approach, Bacillus circulans
      xylanase, is a retaining glycosidase that hydrolyzes xylan or beta-xylobiosides
      through a double-displacement mechanism involving a covalent xylobiosyl-enzyme
      intermediate. A low steady state level of this intermediate formed during the
      hydrolysis of 2,5-dinitrophenyl beta-d-xylobioside was detected by time-resolved
      ESI-MS. The low concentration of this intermediate and its rate of formation did
      not permit pre-steady state kinetic analysis. By contrast, the covalent
      intermediate accumulates fully when the Tyr80Phe mutant hydrolyzes the same
      substrate. Using time-resolved ESI-MS, the pre-steady state kinetic parameters
      for the formation of the covalent intermediate in the mutant xylanase have been
      determined. The kinetic data are in agreement with those determined by monitoring
      the release of 2, 5-dinitrophenol with stopped-flow UV-vis spectroscopy. This
      demonstrates that time-resolved ESI-MS can be used to accurately monitor the pre
      steady state kinetics of enzymatic reactions, with the advantage of identifying
      transient enzyme intermediates by their mass.

PMID- 9601026
TI  - Mapping the promoter DNA sites proximal to conserved regions of sigma 70 in an
      Escherichia coli RNA polymerase-lacUV5 open promoter complex.
AB  - Base-specific interactions between promoter DNA and Escherichia coli RNA
      polymerase are regulated by a sigma (sigma) protein during transcription
      initiation. To map spatial relations between evolutionarily conserved regions of
      the primary sigma (sigma 70) and each DNA strand along the lacUV5 promoter in the
      transcriptionally active "open" complex, we have used a cysteine-tethered cutting
      reagent to cleave DNA strands. The chemical nuclease FeBABE [iron (S)-1-(p
      bromoacetamidobenzyl)ethylenediaminetetraacetate] was conjugated to single
      cysteine mutants of sigma 70 at sites 132C, 376C, 396C, 422C, 496C, 517C, or
      581C. After formation of open promoter complexes between lacUV5 DNA and RNA
      polymerase holoenzymes carrying conjugated sigma 70 subunits, we observed
      promoter DNA cleavage spanning at least 60 bases, between positions -48 and +12.
      The results show that sigma 70 region 2.1, otherwise implicated in core enzyme
      binding, is proximal to the nontemplate strand of lacUV5 DNA between the -10
      promoter element and positions as far downstream of the transcription start site
      as +12. Conserved region 3.2 of sigma 70 is proximal to the template strand near
      the +1 transcription start site, and region 3.1 is positioned between the lacUV5
      10 and -35 promoter elements. We propose a model for the orientation of sigma 70
      and DNA in the open complex.

PMID- 9601027
TI  - Phosphorylation changes the spatial relationship between Glu124-Arg143 and Cys18
      and Cys165 of the regulatory light chain in smooth muscle myosin.
AB  - Regulatory light chain (RLC) mutants, RLC-C18 and RLC-C165, containing a single
      cysteine at positions 18 and 165 near the N and C terminus, respectively, were
      each labeled with benzophenone 4-iodoacetamide and exchanged into myosin in their
      phosphorylated or unphosphorylated forms and then photolyzed. SDS-PAGE showed
      that, for RLC-C18, the intrachain photo-cross-linking in myosin was inhibited by
      phosphorylation. For myosin containing RLC-C165, the yield of one intrachain
      cross-linked band decreased significantly whereas the other was unaffected by
      phosphorylation. Peptide mapping in conjunction with mass spectrometry showed
      that Cys165 was cross-linked to site(s) within Ala17-Lys34 independent of the
      phosphorylation of Ser19. This clearly demonstrates that the proximity between
      the N- and C-terminal regions of RLC is not affected by phosphorylation. In
      addition, Cys165 could also be cross-linked to the region of Phe133-Arg143;
      however, this type of cross-linking was inhibited in the phosphorylated state.
      For RLC-C18, the cross-linking took place with the region of Glu124-Arg132 or
      Phe133-Arg143, also only in the unphosphorylated state. Thus, phosphorylation
      changes the spatial relationship between the region of Glu124-Arg143 and Cys18
      and Cys165. In scallop myosin, the region corresponding to Glu124-Arg143 is
      located at the interfaces between RLC and the essential light chain as well as
      the heavy chain [Xie, X. , et al. (1994) Nature 368, 306-312]. In light of that
      work, our results suggest that the region of Glu124-Arg143 is involved in the
      phosphorylation-dependent signaling and the change in its spatial relationship
      with respect to the N and C termini of RLC may underlie the activation of the
      smooth muscle myosin.

PMID- 9601028
TI  - Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide
      phosphate guanylyltransferase from Salmonella typhimurium determined to 2.3 A
      resolution,.
AB  - The X-ray structure of adenosylcobinamide kinase/adenosylcobinamide phosphate
      guanylyltransferase (CobU) from Salmonella typhimurium has been determined to 2.3
      A resolution. This enzyme of subunit molecular weight 19 770 plays a central role
      in the assembly of the nucleotide loop for adenosylcobalamin where it catalyzes
      both the phosphorylation of the 1-amino-2-propanol side chain of the corrin ring
      and the subsequent attachment of GMP to form the product adenosylcobinamide-GDP.
      The kinase activity is believed to be associated with a P-loop motif, whereas the
      transferase activity proceeds at a different site on the enzyme via a guanylyl
      intermediate. The enzyme was crystallized in the space group C2221 with unit cell
      dimensions of a = 96.4 A, b = 114.4 A, and c = 106.7 A, with three subunits per
      asymmetric unit. The structure reveals that the enzyme is a molecular trimer and
      appears somewhat like a propeller with overall molecular dimensions of
      approximately 64 A x 77 A x 131 A. Each subunit consists of a single domain that
      is dominated by a seven-stranded mixed beta-sheet flanked on either side by a
      total of five alpha-helices and one helical turn. Six of the seven beta-strands
      run parallel. The C-terminal strand lies at the edge of the sheet and runs
      antiparallel to the others. Interestingly, CobU displays a remarkable structural
      and topological similarity to the central domain of the RecA protein, although
      the reason for this observation is unclear. The structure contains a P-loop motif
      located at the base of a prominent cleft formed by the association of two
      subunits and is most likely the kinase active site. Each subunit of CobU contains
      a cis peptide bond between Glu80 and Cys81 where Glu80 faces the P-loop and might
      serve to coordinate the magnesium ion of the triphosphate substrate.
      Interestingly, His46, which is the putative site for guanylylation, lies
      approximately 21 A from the P-loop and is solvent-exposed. This suggests that the
      enzyme undergoes a conformational change when the substrates bind to bring these
      two active sites into closer proximity.

PMID- 9601029
TI  - Relationship between enzyme specificity and the backbone dynamics of free and
      inhibited alpha-lytic protease.
AB  - To better understand the structural basis for the observed patterns in substrate
      specificity, the backbone dynamics of alpha-lytic protease have been investigated
      using 15N relaxation measurements. The enzyme was inhibited with the peptide
      boronic acid N-tert-butyloxycarbonyl-Ala-Pro-boroVal [Kettner, C. A., et al.
      (1988) Biochemistry 27, 7682], which mimics interactions occurring in the
      tetrahedral transition state or nearby intermediates, and the dynamics of the
      unbound and inhibited enzyme were compared. Arrayed 2-D NMR spectra were acquired
      to measure T1, T2, and steady-state ?1H?-15N NOE of >95% of the backbone amides
      in both protein samples. The overall rotational correlation time tauc was found
      to be 8.1 ns. Values of the spectral density function J(omega) at omega = 0,
      omegaN, and approximately omegaH were derived from the relaxation results using
      reduced spectral density mapping [Ishima, R., & Nagayama, K. (1995) Biochemistry
      34, 3162]. The resultant spectral densities were interpreted to indicate regions
      of fast motion (nanosecond to picosecond) and of intermediate chemical exchange
      (millisecond to microsecond). The protein has 13 regions with increased motion on
      the fast time scale; these generally fall on exterior turns and loops and most
      correlate with regions of higher crystallographic B-factors. Several stretches of
      backbone undergo intermediate chemical exchange, indicating motion or other
      processes that cause temporal chemical shift changes. A comparison of spectral
      densities for both the free and inhibited enzymes revealed that inhibitor binding
      preferentially stabilizes regions undergoing chemical exchange (which predominate
      around the active site) and only minimally affect regions of rapid motion. Slow
      motions, suggestive of backbone plasticity, are observed in most of the binding
      pocket residues. This may point to a mechanism for the observed broad specificity
      of the enzyme. The significance of the observed dynamics for substrate binding
      and specificity is discussed.

PMID- 9601030
TI  - Kinetic analyses of mutations in the glycine-rich loop of cAMP-dependent protein
      kinase.
AB  - The conserved glycines in the glycine-rich loop (Leu-Gly50-Thr-Gly52-Ser-Phe
      Gly55-Arg-Val) of the catalytic (C) subunit of cAMP-dependent protein kinase were
      each mutated to Ser (G50S, G52S, and G55S). The effects of these mutations were
      assessed here using both steady-state and pre-steady-state kinetic methods. While
      G50S and G52S reduced the apparent affinity for ATP by approximately 10-fold,
      substitution at Gly55 had no effect on nucleotide binding. In contrast to ATP,
      only mutation at position 50 interfered with ADP binding. These three mutations
      lowered the rate of phosphoryl transfer by 7-300-fold. The combined data indicate
      that G50 and G52 are the most critical residues in the loop for catalysis, with
      replacement at position 52 being the most extreme owing to a larger decrease in
      the rate of phosphoryl transfer (29 vs 1.6 s-1 in contrast to 500 s-1 for wild
      type C). Surprisingly, all three mutations lowered the affinity for Kemptide by
      approximately 10-fold, although none of the loop glycines makes direct contact
      with the substrate. The inability to correlate the rate constant for net product
      release with the dissociation constant for ADP implies that other steps may limit
      the decomposition of the ternary product complex. The observations that G52S (a)
      selectively affects ATP binding and (b) significantly lowers the rate of
      phosphoryl transfer without making direct contact with either the nucleotide or
      the peptide imply that this residue serves a structural role in the loop, most
      likely by positioning the backbone amide of Ser53 for contacting the gamma
      phosphate of ATP. Energy-minimized models of the mutant proteins are consistent
      with the observed kinetic consequences of each mutation. The models predict that
      only mutation of Gly52 will interfere with the observed hydrogen bonding between
      the backbone and ATP.

PMID- 9601031
TI  - rRNA chemical groups required for aminoglycoside binding.
AB  - Through an affinity chromatography based modification-interference assay, we have
      identified chemical groups within Escherichia coli 16S ribosomal RNA sequence
      that are required for binding the aminoglycoside antibiotic paromomycin.
      Paromomycin was covalently linked to solid support via a nine atom spacer from
      the 6"'-amine of ring IV, and chemical modifications to an A-site oligonucleotide
      that disrupted binding were identified. Positions in the RNA oligonucleotide that
      correspond to G1405(N7), G1491(N7), G1494(N7), A1408(N7), A1493(N7), A1408(N1),
      A1492(N1), and A1493(N1), as well as the pro-R phosphate oxygens of A1492 and
      A1493 in 16S rRNA are chemical groups that are essential for a high-affinity RNA
      paromomycin interaction. These data are consistent with genetic, biochemical, and
      structural studies related to neomycin-class antibiotics and provide additional
      information for establishing an exact model for their interaction with the
      ribosome.

PMID- 9601032
TI  - A source of response regulator autophosphatase activity: the critical role of a
      residue adjacent to the Spo0F autophosphorylation active site.
AB  - Two-component signaling systems are used by bacteria, plants, and lower
      eukaryotes to adapt to environmental changes. The first component, a protein
      kinase, responds to a signal by phosphorylating the second component; a response
      regulator protein that often acts by inducing the expression of specific genes.
      Response regulators also have an autophosphatase activity that ensures that the
      proteins are not permanently activated by phosphorylation. The magnitude of this
      activity varies by at least 1000-fold between various response regulators, and
      the molecular features responsible for this varied autophosphatase activity have
      not been clearly defined. Using wild-type and mutant derivatives of the
      sporulation response regulator Spo0F, it has been demonstrated that a key residue
      in determining the magnitude of this activity is that at position 56 of Spo0F
      approximately P; this residue is adjacent to the site of phosphorylation, Asp 54.
      For example, Spo0F approximately P K56N has a 23-fold greater autophosphatase
      activity (t1/2 = 8 min) than wild-type Spo0F approximately P (t1/2 = 180 min). It
      is suggested that, by analogy to the GTPase activity of p21(ras) and by examining
      the crystallographic structure of Spo0F, that the carboxyamide of the mutant Asn
      56 may favorably position a catalytic water near the protein acyl phosphate to
      promote Spo0F approximately P K56N hydrolysis. It is also deduced that Lys 56 in
      the wild-type protein is critical for the efficient interaction and phosphoryl
      transfer between Spo0F and it's cognate protein kinase, KinA. Comparison of the
      known response regulators shows that inefficient autophosphatases (t1/2 on the
      order of hours) typically contain an amino acid residue with a long side chain at
      the position equivalent to 56 in Spo0F, whereas efficient autophosphatases (t1/2
      on the order of minutes) frequently contain a residue with a carboxyamide or
      carboxylate side chain at this position. It appears that, by altering residues
      adjacent to the active site, the autophosphatase activity of response regulator
      proteins has been attenuated to match the diverse biological roles played by
      these proteins.

PMID- 9601033
TI  - Dissection of the sequence specificity of the Holliday junction endonuclease
      CCE1.
AB  - CCE1 is a Holliday (four-way DNA) junction-specific endonuclease which resolves
      mitochondrial DNA recombination intermediates in Saccharomycescerevisiae. The
      junction-resolving enzymes are a diverse class, widely distributed in nature from
      viruses to higher eukaryotes. In common with most other junction-resolving
      enzymes, the cleavage activity of CCE1 is nucleotide sequence-dependent. We have
      undertaken a systematic study of the sequence specificity of CCE1, using a single
      turnover kinetic assay and a panel of synthetic four-way DNA junction substrates.
      A tetranucleotide consensus cleavage sequence 5'-ACT downward arrowA has been
      identified, with specificity residing mainly at the central CT dinucleotide.
      Equilibrium constants for CCE1 binding to four-way junctions are unaffected by
      sequence variations, suggesting that substrate discrimination occurs
      predominantly in the transition state complex. CCE1 cuts most efficiently at the
      junction center, but can also cleave the DNA backbone at positions one nucleotide
      3' or 5' of the point of strand exchange, suggesting a significant degree of
      conformational flexibility in the CCE1:junction complex. Introduction of base
      analogues at single sites in four-way junctions has allowed investigation of the
      sequence specificity of CCE1 in finer detail. In particular, the N7 moiety of the
      guanine base-pairing with the cytosine of the consensus sequence appears to be
      crucial for catalysis. The functional significance of sequence specificity in
      junction-resolving enzymes is discussed.

PMID- 9601034
TI  - Absence of pyridoxine-5'-phosphate oxidase (PNPO) activity in neoplastic cells:
      isolation, characterization, and expression of PNPO cDNA.
AB  - Major differences in the metabolism of vitamin B6 in various cancers compared to
      their normal cellular counterparts have been documented. In particular,
      pyridoxine- 5'-phosphate oxidase (PNPO), the rate-limiting enzyme in pyridoxal 5'
      phosphate (PLP) biosynthesis, is absent in liver and neurally-derived tumors. We
      show that the expression of PNPO is developmentally regulated not only in liver
      but also in brain. Specifically, PNPO activity in fetal brain tissue is 7.5-fold
      lower than that found in adult brain tissue. Furthermore, the isolation and
      characterization of a PNPO cDNA are described. The isolated cDNA was verified to
      be the authentic PNPO cDNA on the basis of two criteria. First, the translated
      product from the PNPO cDNA is immunologically reactive to a polyclonal PNPO
      antibody. Second, PNPO negative hepatoma cell lines stably transfected with the
      PNPO cDNA express enzymatically active PNPO protein. The availability of these
      biological reagents will not only facilitate in depth investigations of the
      reasons for the absence of PNPO in liver and brain malignancies but also aid in
      an understanding of the biochemical regulation of B6 metabolism in development.

PMID- 9601035
TI  - Dissecting the order of bacteriophage T4 DNA polymerase holoenzyme assembly.
AB  - Most biological organisms rely upon a DNA polymerase holoenzyme for processive
      DNA replication. The bacteriophage T4 DNA polymerase holoenzyme is composed of
      the polymerase enzyme and a clamp protein (the 45 protein), which functions as a
      processivity factor by strengthening the interaction between DNA and the
      holoenzyme. The 45 protein must be loaded onto DNA by a clamp loader ATPase
      complex (the 44/62 complex). In this paper, the order of events leading to
      holoenzyme formation is investigated using a combination of rapid-quench and
      stopped-flow fluorescence spectroscopy kinetic methods. A rapid-quench strand
      displacement assay in which the order of holoenzyme component addition is varied
      provided data indicating that the rate-limiting step in holoenzyme assembly is
      associated with the clamp loading process. Pre-steady-state analysis of the clamp
      loader ATPase activity demonstrated that the four bound ATP molecules are
      hydrolyzed stepwise during the clamp loading process in groups of two. Clamp
      loading was examined with stopped-flow fluorescence spectroscopy from the
      perspective of the clamp itself, using a site-specific, fluorescently labeled 45
      protein. A mechanism for T4 DNA polymerase holoenzyme assembly is proposed in
      which the 45 protein interacts with the 44/62 complex leading to the hydrolysis
      of 2 equiv of ATP, and upon contacting DNA, the remaining two ATP molecules bound
      to the 44/62 complex are hydrolyzed. Once all four ATP molecules are hydrolyzed,
      the 45 protein is poised on DNA for association with the polymerase to form the
      holoenzyme.

PMID- 9601036
TI  - The ring fragmentation product of thymidine C5-hydrate when present in DNA is
      repaired by the Escherichia coli Fpg and Nth proteins.
AB  - Various forms of oxidative stress, including gamma-radiolysis and UV irradiation,
      result in the formation of damaged bases. (5R)-Thymidine C5-hydrate is one of
      several modified nucleosides produced from thymidine under these conditions. N-(2
      Deoxy-beta-D-erythro-pentofuranosyl)-N-3-[(2R)-hydroxyisobutyric acid]urea or
      alphaRT is the respective fragmentation product formed from (5R)-thymidine C5
      hydrate upon hydrolysis. This modified nucleoside has potential mutagenic or
      lethal properties. No enzymatic activity responsible for the removal of alphaRT
      has been identified. We report here that when present in DNA, alphaRT is a
      substrate for two purified enzymes from Escherichia coli involved in the repair
      of oxidized bases: the Nth and the Fpg proteins. The Fpg protein removes the
      alphaRT lesion more efficiently than the Nth protein. This is the first example
      of efficient excision of a ring-opened form of a pyrimidine by the Fpg protein.
      The high efficacy of the Fpg protein suggests that it is likely to be involved in
      vivo in the excision of alphaRT. The kinetics of the reaction of the Fpg protein
      with DNA containing alphaRT suggest substrate inhibition. Duplex
      oligodeoxynucleotides containing alphaRT positioned opposite T, dG, dC, and dA
      were cleaved efficiently by both enzymes, although the profiles of activity of
      the two enzymes were different. The Nth enzyme preferentially excises alphaRT
      when opposite a dG, followed by alphaRT.dA, alphaRT. T, and alphaRT.dC. For the
      Fpg protein, the order is alphaRT.dC >/= alphaRT.dG approximately alphaRT.T >
      alphaRT.dA. Moreover, we show that human cell extract exhibits an activity that
      excises alphaRT from an oligonucleotide, suggesting that human homologues of the
      Nth and/or Fpg proteins could be involved in repair of this lesion in human
      cells.

PMID- 9601037
TI  - Evidence of interlipidic ion-pairing in anion-induced DNA release from cationic
      amphiphile-DNA complexes. Mechanistic implications in transfection.
AB  - Complex formation of DNA with a number of cationic amphiphiles has been examined
      using fluorescence, gel electrophoresis, and chemical nuclease digestion. Here we
      have addressed the status of both DNA and lipid upon complexation with each
      other. DNA upon binding with cationic amphiphiles changes its structure in such a
      way that it loses the ability to intercalate and becomes resistant to nuclease
      digestion. Fluorescence anisotropy measurements due to 1, 6-diphenylhexatriene
      (DPH) doped in cationic liposomes demonstrated that upon complexation with DNA,
      the resulting complexes still retain lamellar organizations with modest
      enhancement in thermal stabilities. The lipid-DNA complexation is most effective
      only when the complexation was carried out at or around the phase transition
      temperatures of the cationic lipid employed in the complexation with DNA. The
      release of DNA from cationic lipid-DNA complexes could be induced by several
      anionic additives. Determination of fluorescence anisotropies (due to DPH) as a
      function of temperature clearly demonstrates that the addition of equivalent
      amounts of anionic amphiphile into cationic lipid-DNA complexes leads to the ion
      pairing of the amphiphiles, the melting profiles of which are virtually the same
      as those obtained in the absence of DNA. In this process DNA gets released from
      its complexes with cationic lipids and regains its natural intercalation ability,
      movement, and staining ability on agarose gel and also the sensitivities toward
      nuclease digestion. This clearly suggests that combination of ion-pairing and
      hydrophobic interactions between cationic and anionic amphiphiles is stronger
      than the electrostatic forces involved in the cationic lipid-DNA complexation. It
      is further revealed that the DNA release by anions is most efficient from the
      cationic lipid-DNA complexes at or around the Tm of the cationic lipid used in
      DNA complexation. This explains why more effective DNA delivery is achieved with
      cationic lipids that bear unsaturated hydrocarbon chains than with their
      saturated hydrocarbon counterparts.

PMID- 9601038
TI  - Molecular properties of ClpAP protease of Escherichia coli: ATP-dependent
      association of ClpA and clpP.
AB  - The ClpAP protease from Escherichia coli consists of the ATP-binding regulatory
      component, ClpA (subunit Mr 84 165), and the proteolytic component, ClpP (subunit
      Mr 21 563). Our hydrodynamic studies demonstrate that the predominant forms of
      these proteins in solution correspond to those observed by electron microscopy.
      ClpP and proClpP(SA), which in electron micrographs appear to have subunits
      arranged in rings of seven subunits, were found by ultracentrifugation to have
      s20,w values of 12.2 and 13.2 S and molecular weights of 300 000 and 324 000 +/-
      3000, respectively, indicating that the native form of each consists of two such
      rings. The two intact rings of ClpP were separated in the presence of >/= 0.1 M
      sulfate at low temperatures, suggesting that ring-ring contacts are polar in
      nature and more easily disrupted than subunit contacts within individual rings.
      Sedimentation equilibrium analysis indicated that ClpA purified without
      nucleotide exists as an equilibrium mixture of monomers and dimers with Ka = (1.0
      +/- 0.2) x 10(5) M-1 and that, upon addition of MgATP or adenosine 5'-O-(3
      thiotriphosphate), ClpA subunits associated to a form with Mr 505 000 +/- 5000,
      consistent with the hexameric structure seen by electron microscopy.
      Sedimentation velocity and gel-filtration analysis showed that the nucleotide
      promoted hexamer of ClpA (s20,w = 17.2 S) binds tightly to ClpP producing species
      with s20,w values of 21 and 27 S (f/f0 = 1.5 and 1.8, respectively), consistent
      with electron micrographs of ClpAP that show a single tetradecamer of ClpP
      associated with either one or two ClpA hexamers [Kessel et al. (1995) J. Mol.
      Biol. 250, 587-594]. Under assay conditions in the presence of ATP and Mg2+, the
      apparent dissociation constant of hexameric ClpA and tetradecameric ClpP was
      approximately 4 +/- 2 nM. By the method of continuous variation, the optimal
      ratio of ClpA to ClpP in the active complex was 2:1. The specific activities of
      limiting ClpA and ClpP determined in the presence of an excess of the other
      component indicated that the second molecule of ClpA provides very little
      additional activation of ClpP.

PMID- 9601039
TI  - Formation of a tyrosyl radical in xanthine oxidase.
AB  - Treatment of xanthine oxidase with ferricenium at high pH gives rise to an EPR
      signal not previously seen with this enzyme. The signal is apparently isotropic
      at 9 GHz with a gavg of approximately 2 and once generated is stable to pH 6.0,
      so long as the sample is kept in the dark. Treatment of the signal-giving species
      with hydroxyurea results in complete loss of the signal, indicating that the
      signal is radical-based. Pretreatment of the enzyme with iodoacetate has no
      effect on signal formation with ferricenium. The ferricenium-generated EPR signal
      shows proton hyperfine coupling that is not lost upon exchange into D2O and bears
      considerable resemblance to the tyrosyl radical of the photosynthetic reaction
      center and other systems. These observations lead us to interpret the new
      ferricenium-generated EPR signal of xanthine oxidase as arising from a tyrosyl
      radical, the result of one-electron oxidation of a protein tyrosinate residue.
      Kinetic parameters for the reductive half-reaction of ferricenium-treated
      xanthine oxidase with xanthine were determined by stopped-flow spectrophotometry;
      kred and KDxanthine (15 s-1 and 12 microM, respectively) were essentially
      unchanged. Addition of 2-hydroxy-6-methylpurine (in the presence of 2 mg/mL
      catalase and superoxide dismutase) generated the "very rapid" MoV EPR signal
      while preserving the ferricenium-derived EPR signal, providing a further
      indication that the modified enzyme remains fully functional and the presence of
      the tyrosyl radical does not impact turnover by the enzyme. Coupling of the two
      signals was not evident, nor was coupling to the two 2Fe-2S centers or the flavin
      semiquinone evident. The implications of covalent modifications of proteins
      mediated by ferricenium are discussed.

PMID- 9601040
TI  - Kinetic studies of the branched chain amino acid preferring peptidase activity of
      the 20S proteasome: development of a continuous assay and inhibition by
      tripeptide aldehydes and clasto-lactacystin beta-lactone.
AB  - We have developed an assay to continuously monitor the branched amino acid
      preferring peptidase (BrAAP) activity of the proteasome. This assay is based on
      the hydrolysis of the fluorogenic peptide, Abz-Gly-Pro-Ala-Leu-Ala-Nba (Abz is 2
      aminobenzoyl and Nba is 4-nitrobenzylamide) which is cleaved exclusively at the
      Leu-Ala bond by the 20S proteasome with a kc/Km value of 13 000 M-1 s-1.
      Hydrolysis of this peptide is accompanied by an increase in fluorescence
      intensity (lambda ex = 340 nm, lambda em = 415 nm) due to release of the
      internally quenched 2-aminobenzoyl fluorescence that accompanies diffusion apart
      of the hydrolysis products, Abz-Gly-Pro-Ala-Leu and Ala-Nba. Using this assay, we
      examined inhibition of the BrAAP activity of the proteasome by a series of
      tripeptide aldehydes, Z-Leu-Leu-Xaa-H. When Xaa = Phe, (p-Cl)Phe, and Trp we
      observe biphasic or partial inhibition of the BrAAP activity. In contrast, when
      Xaa = Nva and Leu, simple inhibition kinetics are observed and allow us to
      calculate Ki values of 120 nM and 12 nM, respectively. The inhibitors that
      exhibit simple inhibition kinetics for BrAAP activity are also approximately
      equipotent for inhibition of the chymotrypsin-like (ChT-L) and peptidyl-glutamyl
      peptide hydrolyzing (PGPH) activities, dissociation constants varying by less
      than 25-fold, whereas the inhibitors that exhibit biphasic inhibition kinetics
      for BrAAP activity are >300-fold more potent for inhibiting ChT-L activity than
      for PGPH activity. Inactivation of the BrAAP activity of the proteasome by clasto
      lactacystin beta-lactone is also biphasic. beta-Lactone inactivates approximately
      60% of the BrAAP activity rapidly, with kinetics indistinguishable from its
      inactivation of the chymotrypsin-like activity. The remaining 40% of the BrAAP
      activity is inactivated by beta-lactone at a 50-fold slower rate, with kinetics
      indistinguishable from its inactivation of the PGPH activity. These results
      suggest a mechanism in which hydrolysis of Abz-Gly-Pro-Ala-Leu-Ala-Nba (i.e.,
      BrAAP activity) occurs at two different active sites in the 20S proteasome, and
      that these two active sites are the same ones that catalyze the previously
      described ChT-L and PGPH activities.

PMID- 9601041
TI  - Syntheses of photoactive analogues of adenosine diphosphate
      (hydroxymethyl)pyrrolidinediol and photoaffinity labeling of poly(ADP-ribose)
      glycohydrolase.
AB  - Two isomeric azidoadenosyl analogues of adenosine diphosphate
      (hydroxymethyl)pyrrolidinediol [ADP-HPD; Slama, J. T., et al. (1995) J. Med.
      Chem. 38, 389-393] were synthesized as photoaffinity labels for poly(ADP-ribose)
      glycohydrolase. 8-Azidoadenosine diphosphate (hydroxymethyl)pyrrolidinediol (8-N3
      ADP-HPD) inhibited the enzyme activity by 50% at ca. 1 microM, a concentration 80
      fold lower than that where the isomeric 2-azidoadenosine diphosphate
      (hydroxymethyl)pyrrolidinediol did. [alpha-32P]-8-N3-ADP-HPD was therefore
      synthesized and used to photoderivatize poly(ADP-ribose) glycohydrolase.
      Irradiation of recombinant poly(ADP-ribose) glycohydrolase and low concentrations
      of [alpha-32P]-8-N3-ADP-HPD with short-wave UV light resulted in the covalent
      incorporation of the photoprobe into the protein, as demonstrated by gel
      electrophoresis followed by autoradiography or acid precipitation of the protein
      followed by scintillation counting. No photoincorporation occurred in the absence
      of UV light. The photoincorporation saturated at low concentrations of the
      photoprobe and photoprotection was observed in the presence of low concentrations
      of ADP-HPD, an indication of the specificity of the photoinsertion reaction.
      These results demonstrate that [alpha-32P]-8-N3-ADP-HPD can be used to
      specifically covalently photoderivatize the enzyme to characterize the
      polypetides that constitute the ADP-HPD binding site of poly(ADP-ribose)
      glycohydrolase. The photoincorporation reaction was further used to determine the
      ability of ADP-ribose polymers of varying size to compete with [alpha-32P]-8-N3
      ADP-HPD for binding to the enzyme. Photoincorporation of [alpha-32P]-8-N3-ADP-HPD
      was inhibited by 80% in the presence of low concentrations of short, unbranched
      ADP-ribose oligomers (5-15 ADP-ribose units in length). No similar
      photoprotection was afforded by the addition of a high-molecular weight highly
      branched polymer. These results indicate that the photolabel shares a binding
      site with the short, linear polymer, but not with the long, highly branched
      polymer.

PMID- 9601042
TI  - Extended X-ray absorption fine structure studies of the anion complexes of FeZn
      uteroferrin.
AB  - Molybdate and tungstate are strong inhibitors of the purple acid phosphatases.
      The binding modes of these anions to the FeZn derivative of uteroferrin, the
      purple acid phosphatase from porcine uterus (FeZnUf), have been characterized by
      X-ray absorption spectroscopy at both the iron and zinc K-edges. Pre-edge data
      show that both FeZnUf.MoO4 and FeZnUf.WO4 have six-coordinate iron sites.
      Analysis of the EXAFS regions shows that the iron sites of both molybdate and
      tungstate complexes are best simulated by a shell of three O or N atoms at 2.08
      2.09 A and a shell of two O or N atoms at 1.93-1.95 A. On the other hand, the
      zinc sites have shells of five O or N atoms at approximately 2.1 A and one O or N
      atom at approximately 2.5 A. Because of the higher resolution of the FeZnUf. MoO4
      data, the main shell at approximately 2.1 A can be further split into shells of
      four O or N at 2.04 A and one O or N at 2.22 A, the latter being associated with
      a molybdate oxygen. Outer-sphere EXAFS analysis indicates an Fe-Zn separation of
      approximately 3.4 A for both FeZnUf.MoO4 and FeZnUf.WO4, Fe-Mo/W distances of 3.2
      A, and Zn-Mo/W distances of 3.6-3.7 A. Thus, molybdate and tungstate bridge the
      FeZn active site like phosphate, but do so unsymmetrically. The asymmetric
      bidentate bridging mode of molybdate and tungstate helps explain the effect of
      these anions on the redox properties of the diiron uteroferrin.

PMID- 9601043
TI  - Dynamics of the conformational ensemble of partially folded bovine pancreatic
      trypsin inhibitor.
AB  - A single-disulfide variant of bovine pancreatic trypsin inhibitor (BPTI), [14
      38]Abu, is a partially folded ensemble which includes two, and in one case three,
      conformations that interconvert slowly enough to exhibit separate cross-peaks in
      the amide region of homonuclear and heteronuclear NMR spectra. Each conformation
      is itself composed of many subconformations in rapid equilibrium. Partially
      folded BPTI undergoes local motions that are slow, noncooperative, independent
      fluctuations of short segments within the chain. Cooperative global unfolding of
      the ensemble is also observed. Heteronuclear NMR has been used to measure
      interconversion rate constants of partially folded conformational substates; the
      rate constants differ for each residue and vary over an order of magnitude. For
      local fluctuation, the forward rate constants for amide protons of the
      antiparallel beta-sheet are significantly smaller than the rest of the molecule,
      consistent with other indications that this is the most stable part of the
      partially folded protein. The reverse rate constants also vary; they are the
      highest for Ala 27 in the turn between the strands in the sheet and for Phe 33 in
      the antiparallel beta-sheet. Global unfolding interconversion rate constants vary
      over a 3-fold range, consistent with previously observed deviations from two
      state behavior. Fast backbone dynamics, from T1, T2, and NOE relaxation
      parameters, are obtained for the slowly interchanging conformations in the
      partially folded ensemble. Clear differences are observed between the two
      conformations; one is more flexible and less compact than the other. In the more
      flexible and disordered partially folded conformation, intermediate exchange is
      detected for some backbone amides, namely, those in the central beta-sheet and
      the turn. These same sheet and turn residues are more ordered in the globally
      denatured ensemble as well. Our results suggest that the turn initiates formation
      of a partially folded ensemble in which the slow-exchange core is the most stable
      region and in which segmental fluctuations reflect multiple nuclei for folding of
      the rest of the molecule.

PMID- 9601044
TI  - The structure of the N-terminus of striated muscle alpha-tropomyosin in a
      chimeric peptide: nuclear magnetic resonance structure and circular dichroism
      studies.
AB  - Tropomyosins (TMs) are highly conserved, coiled-coil, actin binding regulatory
      proteins found in most eukaryotic cells. The amino-terminal domain of 284-residue
      TMs is among the most conserved and functionally important regions. The first
      nine residues are proposed to bind to the carboxyl-terminal nine residues to form
      the "overlap" region between successive TMs, which bind along the actin filament.
      Here, the structure of the N-terminus of muscle alpha-TM, in a chimeric peptide,
      TMZip, has been solved using circular dichroism (CD) and two-dimensional proton
      nuclear magnetic resonance (2D 1H NMR) spectroscopy. Residues 1-14 of TMZip are
      the first 14 N-terminal residues of rabbit striated alpha-TM, and residues 15-32
      of TMZip are the last 18 C-terminal residues of the yeast GCN4 transcription
      factor. CD measurements show that TMZip forms a two-stranded coiled-coil alpha
      helix with an enthalpy of folding of -34 +/- 2 kcal/mol. In 2D1H NMR studies at
      15 degrees C, pH 6.4, the peptide exhibits 123 sequential and medium range
      intrachain NOE cross peaks per chain, characteristic of alpha-helices extending
      from residue 1 to residue 29, together with 85 long-range NOE cross peaks arising
      from interchain interactions. The three-dimensional structure of TMZip has been
      determined using these data plus an additional 509 intrachain constraints per
      chain. The coiled-coil domain extends to the N-terminus. Amide hydrogen exchange
      studies, however, suggest that the TM region is less stable than the GCN4 region.
      The work reported here is the first atomic-resolution structure of any region of
      TM and it allows insight into the mechanism of the function of the highly
      conserved N-terminal domain.

PMID- 9601045
TI  - Tyr254 hydroxyl group acts as a two-way switch mechanism in the coupling of
      heterotropic and homotropic effects in Escherichia coli glucosamine-6-phosphate
      deaminase.
AB  - The involvement of tyrosine residues in the allosteric function of the enzyme
      glucosamine 6-phosphate deaminase from Escherichia coli was first proposed on the
      basis of a theoretical analysis of the sequence and demonstrated by
      spectrophotometric experiments. Two tyrosine residues, Tyr121 and Tyr254, were
      indicated as involved in the mechanism of cooperativity and in the allosteric
      regulation of the enzyme [Altamirano et al. (1994) Eur. J. Biochem. 220, 409
      413]. Tyr121 replacement by threonine or tryptophan altered the symmetric
      character of the T --> R transition [Altamirano et al. (1995) Biochemistry 34,
      6074-6082]. From crystallographic data of the R allosteric conformer, Tyr254 has
      been shown to be part of the allosteric pocket [Oliva et al. (1995) Structure 3,
      1323-1332]. Although it is not directly involved in binding the allosteric
      activator, N-acetylglucosamine 6-phosphate, Tyr 254 is hydrogen bonded through
      its phenolic hydroxyl to the backbone carbonyl from residue 161 in the
      neighboring polypeptide chain. Kinetic and binding experiments with the mutant
      form Tyr254-Phe of the enzyme reveal that this replacement caused an uncoupling
      of the homotropic and heterotropic effects. Homotropic cooperativity diminished
      and the allosteric activation pattern changed from one of the K-type in the wild
      type deaminase to a mixed K-V pattern. On the other hand, Tyr254-Trp deaminase is
      kinetically closer to a K-type enzyme and it has a higher catalytic efficiency
      than the wild-type protein. These results show that the interactions of Tyr254
      are fundamental in coupling binding in the active site to events occurring in the
      allosteric pocket of E. coli glucosamine 6-P deaminase.

PMID- 9601046
TI  - Single-tryptophan mutants of monomeric tryptophan repressor: optical spectroscopy
      reveals nonnative structure in a model for an early folding intermediate.
AB  - A monomeric version of the dimeric tryptophan repressor from Escherichia coli,
      L39E TR, has previously been shown to resemble a transient intermediate that
      appears in the first few milliseconds of folding [Shao, X., Hensley, P., and
      Matthews, C. R. (1997) Biochemistry 36, 9941-9949]. In the present study, the
      optical properties of the two intrinsic tryptophans were used to compare the
      structure and dynamics of the monomeric form with those of the native, dimeric
      form. The urea-induced unfolding equilibria of Trp19/L39E TR (Trp99 replaced with
      Phe) and Trp99/L39E TR (Trp19 replaced with Phe) mutants were monitored by
      circular dichroism and fluorescence spectroscopies at pH 7.6 and 25 degrees C.
      Coincident normalized transitions show that the urea denaturation process for
      each single-tryptophan mutant follows a two-state model involving monomeric
      native and unfolded forms. The free energies at standard state in the absence of
      denaturant for Trp19/L39E TR and Trp99/L39E TR are less than that for L39E TR,
      indicating that both tryptophans are involved in stabilizing the monomer.
      Fluorescence and near-UV circular dichroism spectroscopies indicate that the
      tryptophan side chains in monomeric Trp19/L39E TR and Trp99/L39E TR occupy
      hydrophobic, well-structured environments that are distinctively different from
      those found in their dimeric counterparts. Acrylamide quenching experiments show
      that both Trp19 and Trp99 are partially exposed to solvent in the native state,
      with Trp99 having a slightly greater degree of exposure. Measurements of the
      steady-state anisotropies of Trp19/L39E and Trp99/L39E TR demonstrate that the
      motions of both tryptophan side chains are restricted in the folded conformation.
      On the basis of these data, it can be concluded that this monomeric form of the
      tryptophan repressor adopts a well-folded, stable conformation with nonnative
      tertiary structure. When combined with previous results, the current findings
      demonstrate that the development of higher order structure during the folding of
      this intertwined dimer does not follow a simple hierarchical model.

PMID- 9601047
TI  - Alternative models for describing the acid unfolding of the apomyoglobin folding
      intermediate.
AB  - The acid-induced unfolding of the pH 4 intermediate of apomyoglobin (I) is
      described by either of two models: (1) a Monod-Wyman-Changeux-based model (MWC)
      where salt bridges perturb the pKa values of specific ionizable side chains,
      causing unfolding of I as these salt bridges are broken at low pH, and (2) the
      Linderstrom-Lang smeared charge model (L-L), which attributes acid unfolding of I
      to charge repulsion caused by the accumulation of positive charge on the surface
      of the protein. Both models fit earlier acid unfolding data well, but they make
      differing predictions about the effects of electrostatic mutants, which have been
      made and tested. Deletions of positive charge within I are found to stabilize I,
      but disruptions of potential salt bridges have little effect. These results show
      that the acid unfolding of I (I<-->U) is largely caused by generalized charge
      effects rather than by the loss of specific salt bridges. Acid unfolding of the
      native form, which is caused largely by a single histidine with a severely
      depressed pKa, is a sensitive indicator of changes in stability produced by
      mutations. In contrast, the I <--> U transition is caused by a number of groups
      with smaller pKa perturbations and both models predict that the pH midpoint of
      the I right harpoon over left harpoon U transition is an insensitive indicator of
      stability. This result reconciles previous conflicting results, in urea and acid
      unfolding studies of hydrophobic contact mutants, by showing that changes in the
      stability of I are poorly detected by acid unfolding.

PMID- 9601048
TI  - Phosphorylation-induced structural change in phospholamban and its mutants,
      detected by intrinsic fluorescence.
AB  - We have used intrinsic fluorescence to test the hypothesis that phosphorylation
      induces a conformational change in phospholamban (PLB), a regulatory protein in
      cardiac sarcoplasmic reticulum (SR). Phosphorylation of PLB, which relieves
      inhibition of the cardiac Ca-ATPase, has been shown to decrease the mobility of
      PLB in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In
      the present study, we found that this mobility shift depends on the acrylamide
      concentration in the gel, suggesting that phosphorylation increases the effective
      Stokes radius. To further characterize this structural change, we performed
      spectroscopic experiments under the conditions of SDS-PAGE. CD indicated that
      phosphorylation at Ser-16 does not change PLB's secondary structure
      significantly. However, the fluorescence of Tyr-6 in the cytoplasmic domain of
      PLB changed significantly upon PLB phosphorylation: phosphorylation increased the
      fluorescence quantum yield and decreased the quenching efficiency by acrylamide,
      suggesting a local structural change that decreases the solvent accessibility of
      Tyr-6. A point mutation (L37A) in the transmembrane domain, which disrupts PLB
      pentamers and produces monomers in SDS-PAGE and in lipid bilayers, showed similar
      phosphorylation effects on fluorescence, indicating that subunit interactions
      within PLB are not crucial for the observed conformational change in SDS. When
      PLB was reconstituted into dioleoylphosphatidylcholine (DOPC) lipid bilayers,
      similar phosphorylation effects in fluorescence were observed, suggesting that
      PLB behaves similarly in response to phosphorylation in both detergent and lipid
      environments. We conclude that phosphorylation induces a structural change within
      the PLB protomer that decreases the solvent accessibility of Tyr-6. The
      similarity of this structural change in monomers and pentamers is consistent with
      models in which the PLB monomer is sufficient for the phosphorylation-dependent
      regulation of the Ca-ATPase.

PMID- 9601049
TI  - Structural features of the UCCG and UGCG tetraloops in very short hairpins as
      evidenced by optical spectroscopy.
AB  - Structures of the UCCG and UGCG tetraloops formed in octamer ribonucleotidic
      hairpin sequences, i.e., 5'-r[GC(UCCG)GC]-3' and 5'-r[GC(UGCG)GC]-3', have been
      studied in aqueous solution by methods of optical spectroscopy. UV absorption
      melting profiles of these short hairpins, containing only two closing GC base
      pairs in the stem, are consistent with a monophasic, completely reversible order
      to-disorder transition and clearly confirm their unusual structural stability
      (with Tm congruent with 50 degrees C). To establish structural characteristics of
      these tetraloops, Raman and FTIR spectroscopies have been used and vibrational
      conformation markers arising from the phosphate backbone and various nucleosides
      have been analyzed. They have been assigned on the basis of known unambiguous
      vibrational markers established for DNA and RNA chains. Surprisingly, they are
      easily transferable to short oligonucleotidic sequences. Intensities and
      wavenumbers of these conformation markers have been monitored in the 0-70 degrees
      C temperature range, i.e., in going from an ordered to a disordered structure.
      The main structural features of the UCCG and UGCG tetraloops are similar to those
      previously found in the UUCG and UACG tetraloops by means of NMR and vibrational
      spectroscopies, except those of the second nucleosides of the tetraloops (rC and
      rG, respectively) which adopt a 3'-endo/anti rather than a 2'-endo/anti
      conformation.

PMID- 9601050
TI  - Delineation of the Cdc42/Rac-binding domain of p21-activated kinase.
AB  - p21-activated kinases (PAKs) serve as effector proteins for the GTP-binding
      proteins Cdc42 and Rac. They are serine/threonine kinases containing the
      Cdc42/Rac interactive binding (CRIB) motif. The main aim of this study was to
      define the minimal domain of alphaPAK required for Cdc42/Rac binding. Eight
      stable PAK fragments of varying lengths, each containing the CRIB motif (residues
      75-88), were expressed in Escherichia coli, and their ability to interact with
      Cdc42 and Rac was assessed using scintillation proximity assays, isothermal
      titration calorimetry, and fluorescence techniques. The shortest fragments
      examined (residues 70-94 and 75-94) bound only weakly to either Cdc42 or Rac. A
      longer fragment starting at residue 75 and ending at residue 105 showed binding
      to Q61L Rac.GTP with Kd = 1.9 microM. Highest affinity binding (Kd approximately
      0.05 microM) was seen with longer fragments ending at residue 118 or 132. A small
      increase in affinity was seen with those fragments starting at residue 70 rather
      than residue 75. PAK fragments bound with approximately 3-10-fold higher affinity
      to Cdc42 than to Rac and bound Q61L variants with 5-10-fold higher affinity than
      wild type. The dissociation rates of Q61L Rac.mant-GTP and of Q61L Cdc42. mant
      GTP from PAK fragment residues 70-132 were measured to be 0.66 and 0.25 min-1,
      respectively, which are 100-fold lower than dissociation rates for Ras:Ras
      effector domains, although their affinities are similar. Calorimetric
      measurements revealed that binding was associated with a relatively slow heat
      change. It is suggested that these PAK fragments (in the absence of Cdc42 or Rac)
      might exist predominantly in an inactive conformation that slowly interconverts
      with an active conformation and/or a slow conformational change may occur upon
      binding to Cdc42/Rac. In conclusion, the PAK CRIB motif itself is insufficient
      for high-affinity binding to Cdc42/Rac, but a 30 amino acid region of PAK
      (residues 75-105), containing this motif, is sufficient.

PMID- 9601051
TI  - Sequences within apolipoprotein(a) kringle IV types 6-8 bind directly to low
      density lipoprotein and mediate noncovalent association of apolipoprotein(a) with
      apolipoprotein B-100.
AB  - Lipoprotein(a) [Lp(a)] particle formation is a two-step process in which initial
      noncovalent interactions between apolipoprotein(a) [apo(a)] and the
      apolipoprotein B-100 (apoB-100) component of low-density lipoprotein (LDL)
      precede disulfide bond formation. To identify kringle (K) domains in apo(a) that
      bind noncovalently to apoB-100, the binding of a battery of purified recombinant
      apo(a) [r-apo(a)] species to immobilized human LDL has been assessed. The 17K
      form of r-apo(a) (containing all 10 types of kringle IV sequences) as well as
      other truncated r-apo(a) derivatives exhibited specific binding to a single class
      of sites on immobilized LDL, with Kd values ranging from approximately 340 nM
      (12K) to approximately 7900 nM (KIV5-8). The contribution of kringle IV types 6-8
      to the noncovalent interaction of r-apo(a) with LDL was demonstrated by the
      decrease in binding affinity observed upon sequential removal of these kringle
      domains (Kd approximately 700 nM for KIV6-P, Kd approximately 2000 nM for KIV7-P,
      Kd approximately 5100 nM for KIV8-P, and no detectable specific binding of KIV9
      P). Interestingly, KIV9 also appears to participate in the noncovalent binding of
      apo(a) to LDL since the binding of KIV5-8 (Kd approximately 7900 nM) was
      considerably weaker than that of KIV5-9 (Kd approximately 2000 nM). Finally, it
      is demonstrated that inhibition of Lp(a) assembly by proline, lysine, and lysine
      analogues, as well as by arginine and phenylalanine, is due to their ability to
      inhibit noncovalent association of apo(a) and apoB-100 and that these compounds
      directly exert their effects primarily through interactions with sequences
      contained within apo(a) kringle IV types 6-8. On the basis of the obtained data,
      a model is proposed for the interaction of apo(a) and LDL in which apo(a)
      contacts the single high-affinity binding site on apoB-100 through multiple,
      discrete interactions mediated primarily by kringle IV types 6-8.

PMID- 9601052
TI  - Stabilization of charge separation and photochemical misses in photosystem II.
AB  - Illumination of photosystem II by a saturating short flash results in a
      stabilized charge separation in only about 90% of the reaction centers. During a
      series of flashes, the 10% fraction of "photochemical misses" is randomly
      redistributed among the centers. This phenomenon is investigated in DCMU
      inhibited material, eliminating the contribution to misses due to electron
      transfer equilibrium on the quinone acceptors. Under such conditions, the miss
      coefficient is about 5% and is enhanced to about 40% in the presence of
      hydroxylamine at low pH. When a second flash is fired, its efficiency increases
      as a function of the time delay after the first flash (turnover experiments).
      This process involves three distinct time domains: <10 micros, 100 micros, and 10
      ms. From a study of the 515-nm field-indicating change, it appears that the
      increased inefficiency caused by hydroxylamine is not due to a lesser amount of
      initial charge separation but to a recombination process concomitant with the 100
      micros phase of the turnover. The slow turnover phase (10 ms) is not associated
      with a recombination or any other electron transfer event but reflects a
      modification of open centers during which their probability to achieve charge
      stabilization rather than recombination is progressively increased. These results
      are interpreted in terms of an equilibrium between two conformational states of
      the centers endowed with different stabilization yield ("good" and "bad "
      stabilizers). The 100 micros turnover phase is due to the reopening of the bad
      stabilizers by recombination, and the 10 ms phase accompanies the redistribution
      of these centers among the two conformational states.

PMID- 9601054
TI  - Control of androgen biosynthesis in the human through the interaction of Arg347
      and Arg358 of CYP17 with cytochrome b5.
AB  - The lyase activity of human CYP17 (17alpha-hydroxylase-17,20-lyase also P-450c17
      or P-45017alpha) is greatly dependent on the presence of cytochrome b5, and this
      effect has been ascribed an important regulatory role [Lee-Robichaud, Wright,
      Akhtar and Akhtar (1995) Biochem. J. 308, 901-908]. This facet was further
      investigated by site-directed mutagenesis of selected basic residues of human
      CYP17. The purified mutant proteins were subjected to detailed kinetic analysis.
      It was found that the mutation of Lys83, Arg347 and Arg358 produced proteins that
      were deficient in their responsiveness to cytochrome b5, and the effect was most
      pronounced for the two arginine mutants (Arg347-->His and Arg358-->Gln) which
      have been found in male patients suffering from genital ambiguity. These residues
      are invoked to mediate protein-protein interaction between cytochrome b5 and
      CYP17, which 'awakens' the lyase activity of the enzyme required for androgen
      formation.

PMID- 9601053
TI  - The extended protein kinase C superfamily.
AB  - Members of the mammalian protein kinase C (PKC) superfamily play key regulatory
      roles in a multitude of cellular processes, ranging from control of fundamental
      cell autonomous activities, such as proliferation, to more organismal functions,
      such as memory. However, understanding of mammalian PKC signalling systems is
      complicated by the large number of family members. Significant progress has been
      made through studies based on comparative analysis, which have defined a number
      of regulatory elements in PKCs which confer specific location and activation
      signals to each isotype. Further studies on simple organisms have shown that PKC
      signalling paradigms are conserved through evolution from yeast to humans,
      underscoring the importance of this family in cellular signalling and giving
      novel insights into PKC function in complex mammalian systems.

PMID- 9601055
TI  - A novel transforming growth factor beta2 antisense transcript in mammalian lung.
AB  - Transforming growth factor (TGF) beta2 gene expression was examined in murine,
      rat and human lung by in situ hybridization with riboprobes. Hybridization signal
      was observed in a variety of cells with the sense probe, and Northern-blot
      analysis with this probe demonstrated the presence of a novel 3.5 kb transcript.
      This first report suggesting the existance of a natural TGFbeta2 antisense
      transcript raises the possibility that such a transcript may play a role in
      regulating TGFbeta2 production.

PMID- 9601056
TI  - cDNA cloning, genomic organization and chromosomal localization of human heparan
      glucosaminyl N-deacetylase/N-sulphotransferase-2.
AB  - The cDNA and gene encoding human heparan glucosaminyl N-deacetylase/N
      sulphotransferase-2 have been cloned. The cDNA encoded a protein of 883 amino
      acids that was 94% similar to heparan N-sulphotransferase-2 from mouse mast
      cells. Comparison of the deduced amino acid sequences of human heparan N
      sulphotransferase-1 and -2 showed that the enzymes were 70% similar; greater than
      90% of the amino acids between residues 418 and 543 were identical. The least
      conserved amino acids were found in the N-terminus/putative transmembrane regions
      of the two enzymes. The human heparan N-sulphotransferase-2 gene was localized to
      chromosome arm 10q (band 10q22) by in situ fluorescent hybridization. The gene
      contains 13 exons spanning 6.5 kb, ranging in size from 88 bp (exon 2) to >1 kb
      (exon 1), and 12 introns, which were found to occur at similar sites within the
      coding sequence of the human heparan N-sulphotransferase-1 gene. The structure of
      the two genes differed in that the heparan N-sulphotransferase-1 gene contained
      one additional intron. The similarity of the heparan N-sulphotransferase-1 and -2
      proteins and their similar exon-intron organization suggest that they derive from
      a common ancestral gene.

PMID- 9601057
TI  - Mapping the epitope of a functional P-selectin monoclonal antibody (LYP20) to a
      short complement-like repeat (SCR 4) domain: use of human-mouse chimaera and
      homologue-replacement mutagenesis.
AB  - P-selectin (CD62P), an adhesion molecule localized in platelet alpha-granules and
      endothelial cell Weibel-Palade bodies, is rapidly expressed on the surface of
      activated cells. This adhesion molecule, a member of the selectin family,
      mediates leucocyte interactions with activated platelets or endothelial cells.
      The aim of this study was to identify and characterize the epitope of a
      functional blocking P-selectin monoclonal antibody (mAb), LYP20. LYP20 recognizes
      human or rat, but not mouse, P-selectin. Human/mouse chimaeras and wild-type
      constructs, modified by homologue replacement mutagenesis, were expressed in COS
      cells. Blocking anti-(P-selectin) mAbs (G1, G3 or CLB-thromb/6) were observed, by
      flow cytometry, to bind to the lectin-like domain. In contrast, LYP20 was found
      to bind to one of the P-selectin short complement-like repeats (SCR domain 4).
      Homologue replacement mutagenesis of SCR domain 4 (region delineated by amino
      acid residues 359-457) identified three amino acids (Cys412-->Ser, Cys416-->Ser
      or Arg415-->Lys) as being implicated in the LYP20 epitope. Deleting the region
      bearing the LYP20 epitope, from a wild-type CD62P construct, showed a decrease in
      polymorphonuclear leucocyte (PMNL) binding to transfected COS cells. In addition,
      mutation of one of the three amino acids, implicated in the LYP20 epitope,
      markedly affected PMNL binding to transfected COS cells but did not affect the
      binding of mAbs G1 and CLB-thromb/6. These results are the first to indicate (1)
      that a functional blocking anti-P-selectin mAb binds to SCR 4, a site other than
      the lectin-like/epidermal growth factor-like domain, and (2) that SCR domain 4
      has a functional role in P-selectin-leucocyte interactions.

PMID- 9601058
TI  - Proteasome activities decrease during dexamethasone-induced apoptosis of
      thymocytes.
AB  - The induction of apoptosis in thymocytes by the glucocorticoid dexamethasone was
      used as a model system to investigate whether there are changes in 20 S and 26 S
      proteasome activities during apoptosis. We observed that thymocytes contain high
      concentrations of proteasomes and that following treatment with dexamethasone,
      cell extracts showed a decrease in proteasome chymotrypsin-like activity which
      correlated with the degree of apoptosis observed. The decrease in chymotrypsin
      like activity of 20 S and 26S proteasomes was still apparent after these
      complexes had been partially purified from apoptotic thymocyte extracts and was
      therefore not due to competition resulting from a general increase in protein
      turnover. The trypsin-like and peptidylglutamylpeptide hydrolase activities of
      proteasome complexes were also observed to decrease during apoptosis, but these
      decreases were reversed by the inhibition of apoptosis by the caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone. However, the chymotrypsin
      like activity of proteasomes decreased further in the presence of the apoptosis
      inhibitor. Val-Ala-Asp-fluoromethylketone was found to inhibit the chymotrypsin-
      and trypsin-like activity of 26 S proteasomes in vitro. The decrease in
      proteasome activities in apoptosis did not appear to be due to a decrease in the
      concentration of total cellular proteasomes. Thus, the early decreases in 20 S
      and 26 S proteasome activities during apoptosis appear to be due to a down
      regulation of their proteolytic activities and not to a decrease in their protein
      concentration. These data suggest that proteasomes may be responsible, in
      thymocytes, for the turnover of a protein that functions as a positive regulator
      of apoptosis.

PMID- 9601060
TI  - Purification and characterization of a novel chitinase-lysozyme, of another
      chitinase, both hydrolysing Rhizobium meliloti Nod factors, and of a pathogenesis
      related protein from Medicago sativa roots.
AB  - The symbiosis between Rhizobium meliloti and Medicago sativa (Leguminosae)
      involves the interaction of lipochito-oligosaccharides (Nod factors) excreted by
      bacteria with specific proteins of the host plant. The cleavage of Nod factors
      can be used as an enzymic assay to identify novel hydrolytic enzymes. Here a
      soluble extract of 3-day-old roots was fractionated by anion exchange, affinity
      chromatography, gel filtration and native electrophoresis. Two acidic chitinases
      (pI 4.6-5.4), CHIT24 and CHIT36, designated in accordance with their molecular
      mass in kDa, were separated. CHIT24 cleaves all tested Nod factors to produce
      lipotrisaccharides with the preference NodRm-V(S)>NodRm-IV >NodRm-IV(S)>=NodRm
      IV(Ac,S); it also hydrolyses colloidal 3H-chitin and has lysozyme activity. The
      kinetics of Nod factor degradation by CHIT24 depends on substrate structural
      parameters, namely the length of the oligosaccharide chain and sulphation (S) at
      the reducing end, but not much on acetylation (Ac) at the non-reducing end. The
      25-residue N-terminal sequence of CHIT24 has no similarity with known chitinases
      or lysozymes, indicating that it is a novel type of hydrolase. CHIT36 also
      hydrolyses NodRm-V(S) into NodRm-III, but it is inactive towards NodRm-IV(S) and
      NodRm-IV(Ac,S) formed by R. meliloti. Finally, a 17 kDa protein, P17, was co
      purified with CHIT24. It neither degrades Nod factors nor exhibits lysozyme
      activity and shows complete identity, at the 15-residue N-terminal sequence, with
      a class 10 pathogenesis-related protein, PR-10.

PMID- 9601059
TI  - Overexpression of myristoylated alanine-rich C-kinase substrate enhances
      activation of phospholipase D by protein kinase C in SK-N-MC human neuroblastoma
      cells.
AB  - Signal transduction can involve the activation of protein kinase C (PKC) and the
      subsequent phosphorylation of protein substrates, including myristoylated alanine
      rich C kinase substrate (MARCKS). Previously we showed that stimulation of
      phosphatidylcholine (PtdCho) synthesis by PMA in SK-N-MC human neuroblastoma
      cells required overexpression of MARCKS, whereas PKCalpha alone was insufficient.
      We have now investigated the role of MARCKS in PMA-stimulated PtdCho hydrolysis
      by phospholipase D (PLD). Overexpression of MARCKS enhanced PLD activity 1.3-2.5
      fold compared with vector controls in unstimulated cells, and 3-4-fold in cells
      stimulated with 100 nM PMA. PMA-stimulated PLD activity was blocked by the PKC
      inhibitor bisindolylmaleimide. Activation of PLD by PMA was linear with time to
      60 min, whereas stimulation of PtdCho synthesis by PMA in clones overexpressing
      MARCKS was observed after a 15 min time lag, suggesting that the hydrolysis of
      PtdCho by PLD preceded synthesis. The formation of phosphatidylbutanol by PLD was
      greatest when PtdCho was the predominantly labelled phospholipid, indicating that
      PtdCho was the preferred, but not the only, phospholipid substrate for PLD. Cells
      overexpressing MARCKS had 2-fold higher levels of PKCalpha than in vector control
      cells analysed by Western blot analysis; levels of PKCbeta and PLD were similar
      in all clones. The loss of both MARCKS and PKCalpha expression at higher
      subcultures of the clones was paralleled by the loss of stimulation of PLD
      activity and PtdCho synthesis by PMA. Our results show that MARCKS is an
      essential link in the PKC-mediated activation of PtdCho-specific PLD in these
      cells and that the stimulation of PtdCho synthesis by PMA is a secondary
      response.

PMID- 9601061
TI  - Haem insertion, dimerization and reactivation of haem-free rat neuronal nitric
      oxide synthase.
AB  - The nitric oxide synthases are dimeric enzymes in which the intersubunit contacts
      are formed by the P-450-haem-containing, tetrahydrobiopterin-dependent oxygenase
      domain. The dimerization of the neuronal isoenzyme was shown previously to be
      triggered by Fe-protoporphyrin IX (haemin). We report for the first time the
      reactivation of the haem-deficient neuronal isoenzyme (from rat, expressed in a
      baculovirus/insect cell system) after haem reconstitution. We further examined
      the reconstitution of the enzyme with protoporphyrin IX (PPIX) and its Mn and Co
      complexes. All of these porphyrins inserted into the haem pocket, as assessed by
      quenching of intrinsic protein fluorescence. In addition to haemin, MnPPIX
      stimulated dimerization, as measured by gel filtration and by cross-linking with
      glutaraldehyde. In contrast, neither CoPPIX nor PPIX stimulated dimerization. The
      absorbance spectra of the reconstituted enzymes were measured and compared with
      published results on P-450 enzymes reconstituted with the same metals. The
      results suggest that those metalloporphyrins which caused dimerization were able
      to acquire a thiolate ligand from the protein, and we propose that this ligation
      is the trigger for dimerization. Substrate and tetrahydrobiopterin binding sites
      only emerged with the metalloporphyrins that caused dimerization.

PMID- 9601062
TI  - Quantitative assessment of comparative potencies of cholesterol-crystal-promoting
      factors: relation to mechanistic characterization.
AB  - The crystallization of cholesterol is affected by various factors in bile. The
      present study evaluated the relative importance of cholesterol-nucleation
      promoting factors and partially characterized the mechanisms of their action.
      Model biles with an identical relative composition of cholesterol, egg-yolk
      phosphatidylcholine and taurocholate, except for replacing phosphatidylcholine (5
      20%) with dilinoleoyl-phosphatidylcholine or taurocholate (10-30%) with
      taurodeoxycholate. Cholesterol crystallization was quantitatively assessed
      spectrophotometrically and morphologically estimated by the laser-scattering
      diffraction analyser and video-enhanced microscopy in the absence and presence of
      concanavalin A-binding glycoprotein isolated from human bile. In a series of
      experiments, lipid distribution among particulate species was determined after
      isolation by FPLC. In all experiments, cholesterol crystallization was dose
      dependently enhanced with a rank order of: concanavalin A-binding glycoprotein >
      dilinoleoyl - phosphatidyl choline> taurodeoxycholate. No morphological
      alteration was evident for vesicles and crystals, but the
      cholesterol/phospholipid ratio in vesicles was increased significantly by
      replacement with dilinoleoyl-phosphatidylcholine and excess cholesterol. A high
      proportion of relatively hydrophilic phosphatidylcholine species such as
      dilinoleoyl-phosphatidylcholine and excess cholesterol in bile cause a
      redistribution of cholesterol to increase a vesicular cholesterol/phospholipid
      ratio, eventually promoting cholesterol crystallization, whereas concanavalin A
      binding glycoprotein acts via differing mechanisms.

PMID- 9601063
TI  - Rabbit cardiac and skeletal myocytes differ in constitutive and inducible
      expression of the glucose-regulated protein GRP94.
AB  - The glucose-regulated protein GRP94 is a stress-inducible glycoprotein that is
      known to be constitutively and ubiquitously expressed in the endoplasmic
      reticulum of mammalian cells. From a rabbit heart cDNA library we isolated four
      overlapping clones coding for the rabbit homologue of GRP94 mRNA. Northern blot
      analysis shows that a 3200 nt mRNA species corresponding to GRP94 mRNA is
      detectable in several tissues and it is 5-fold more abundant in the heart than in
      the skeletal muscle. Hybridization analysis in situ shows that GRP94 mRNA
      accumulates in cardiac myocytes, whereas in skeletal muscles it is not detectable
      in myofibres. A monoclonal antibody raised by using a 35 kDa recombinant GRP94
      polypeptide as immunogen detects a single reactive polypeptide of 94 kDa in a
      Western blot of liver and heart homogenates and does not react with skeletal
      muscle homogenates. Conversely, GRP94 mRNA and protein are detectable in both
      cardiac and skeletal muscle myocytes of fetal and neonatal rabbits. After 24 h of
      endotoxin administration to adult rabbits, GRP94 mRNA accumulation increases 3
      fold in both heart and skeletal muscle and it is followed by a comparable
      increase in protein accumulation. However, hybridization and immunohistochemistry
      in situ do not reveal any change in the expression of GRP94 mRNA and protein in
      skeletal muscle myocytes after endotoxin treatment. Thus skeletal muscle fibres
      display a unique regulation of the GRP94 gene, which is up-regulated during
      perinatal development, whereas in the adult animal it is apparently silent and
      not responsive to endotoxin treatment.

PMID- 9601064
TI  - Effect of tri-iodothyronine on leptin release and leptin mRNA accumulation in rat
      adipose tissue.
AB  - Leptin, the product of the obese gene, is produced by white adipocytes. The
      release of leptin, as well as leptin mRNA content, was enhanced in adipocytes
      isolated from hypothyroid rats. The administration of tri-iodothyronine (T3) 8 h
      before death inhibited leptin release by adipocytes incubated for 6 or 24 h.
      Direct addition of T3 to pieces of adipose tissue enhanced the loss of leptin
      mRNA seen over 24 h in the presence of dexamethasone plus the beta3-adrenergic
      agonist Cl 316,243. In contrast, if pieces of adipose tissue were incubated with
      dexamethasone plus insulin, enhanced the T3 accumulation of leptin mRNA. These
      results indicate that T3 enhances net adipocyte leptin mRNA accumulation in a
      condition that approximates the fed state (presence of insulin) but inhibits
      leptin mRNA accumulation in a condition that approximates the fasted state
      (absence of insulin).

PMID- 9601065
TI  - Salicortin: a repeat-attack new-mechanism-based Agrobacterium faecalis beta
      glucosidase inhibitor.
AB  - Salicortin, a natural product abundant in most members of the Salicaceae family,
      is a mechanism-based inactivator of Agrobacterium faecalis beta-glucosidase.
      Inactivation is delayed in the presence of competitive inhibitors, thereby
      demonstrating the requirement for an enzyme-bound salicortin before inactivation.
      Product studies suggest that inactivation proceeds via a quinone methide
      intermediate formed by the fragmentation of the aglycone of salicortin while it
      is bound to the enzyme. Tryptic digest and HPLC/MS studies confirm the role of
      quinone methide attack and also show that the enzyme undergoes multiple
      modifications. In addition, when the inactivation was run in the presence of a
      mutant inactive form of the enzyme, HPLC/MS analyses clearly showed no
      modification of the mutant enzyme, demonstrating that the quinone methide does
      not exist in free solution and suggesting that inactivation is active-site
      directed.

PMID- 9601066
TI  - Overlapping antioxidant response element and PMA response element sequences
      mediate basal and beta-naphthoflavone-induced expression of the human gamma
      glutamylcysteine synthetase catalytic subunit gene.
AB  - gamma-Glutamylcysteine synthetase (GCS), the rate-limiting enzyme in the de novo
      synthesis of GSH, is a heterodimer, consisting of a catalytic (GCSh) and a
      regulatory subunit (GCSl). We previously demonstrated that the constitutive and
      beta-naphthoflavone (beta-NF)-induced expression of the GCSh gene is mediated by
      a distal antioxidant response element (ARE), ARE4, located 3.1 kb upstream of the
      transcriptional start site [Mulcahy, Wartman, Bailey and Gipp (1997) J. Biol.
      Chem. 272, 7445-7454]. ARE4 consists of a consensus ARE sequence (5'-GTGACTCAGCG
      3') containing an embedded PMA-responsive element (TRE, underlined). The relative
      significance of the two overlapping response elements to constitutive and beta-NF
      induced expression of the GCSh gene was determined by mutational analyses. The
      internal activator protein-1 (AP-1)-binding sequence mediated constitutive
      expression of promoter/reporter transgenes, but was not required for beta-NF
      responsiveness. In gel-shift experiments, the TRE was necessary for binding of
      proteins from nuclear extracts prepared from untreated HepG2 cells. In contrast,
      induction by beta-NF was dependent on an intact ARE sequence, particularly the
      terminal GC box of ARE4. The GC box of ARE4 was shown to be essential for both
      basal and beta-NF-induced expression of reporter constructs. This element also
      influenced binding of nuclear proteins to ARE4, specifically in extracts isolated
      from beta-NF-treated HepG2 cells. Because previous studies indicated that ARE4
      may co-operate with a separate putative ARE, the role of the neighbouring
      sequence (ARE3), located 34 bases downstream of ARE4, was also evaluated.
      Mutation of this element within a GCSh promoter/reporter did not modify the basal
      or beta-NF-induced expression of the transgene, demonstrating that ARE3 does not
      influence the constitutive or beta-NF-induced expression of the GCSh gene.

PMID- 9601067
TI  - Isolation and characterization of the human aldehyde oxidase gene: conservation
      of intron/exon boundaries with the xanthine oxidoreductase gene indicates a
      common origin.
AB  - Aldehyde oxidase (AO) is a molybdo-flavo enzyme involved in the metabolism of
      various endogenous and exogenous N-heterocyclic compounds of pharmacological and
      toxicological importance. The enzyme is the product of a gene which is implicated
      in the aetio-pathogenesis of familial recessive amyotrophic lateral sclerosis.
      Here, we report the cloning and structural characterization of the human AO gene.
      AO is a single copy gene approximately 85 kb long with 35 transcribed exons. The
      transcription-initiation site and the sequence of the 5'-flanking region,
      containing several putative regulatory elements, were determined. The 5'-flanking
      region contains a functional promoter, as assessed by appropriate reporter
      constructs in transient transfection experiments. Comparison of the AO gene
      structure shows conservation of the position and type of exon/intron junctions
      relative to those observed in the gene coding for another molybdo-flavoprotein,
      i.e. xanthine oxidoreductase (XOR). As the two genes code for proteins with a
      high level of amino acid identity, our results strongly suggest that the AO and
      XOR genetic loci arose as the consequence of a duplication event. Southern blot
      analysis conducted on genomic DNA from various animal species with specific cDNA
      probes indicates that the AO gene is less conserved than the XOR gene during
      evolution.

PMID- 9601068
TI  - Characterization of the functional properties of smooth muscle caldesmon domain
      4a: evidence for an independent inhibitory actin-tropomyosin binding domain.
AB  - Recent analysis has shown the presence of three sequences in the C-terminal 170
      amino acids of human caldesmon (domain 4) which are involved in actin binding and
      tropomyosin-dependent inhibition of actomyosin ATPase. Two are in domain 4b
      (amino acids 715-793) and one is in domain 4a (amino acids 636-714). In the
      present work we have compared recombinant peptides containing either domain 4a or
      domain 4b to address the question as to whether domain 4a alone has any
      inhibitory activity. We have produced three new recombinant fragments containing
      domain 4a: H10 [622-708], H12 [506-708] and H13 [622-726] and we have
      characterized their functional properties. All three fragments bound to actin and
      tropomyosin. Caldesmon, but not domain 4b, was able to displace the fragments
      H10, H12 and H13 from actin. Thus the isolated caldesmon domain 4a peptides bind
      to the same region on actin as in the whole molecule while domains 4a and 4b
      occupy different sites on the actin molecule. Unlike domain 4b, none of the
      domain 4a fragments inhibited the actomyosin ATPase in the absence of
      tropomyosin. However both domain 4a and 4b fragments displayed an inhibitory
      activity in the presence of tropomyosin. H13 and H12 were more potent inhibitors
      than H10. Ca2+-calmodulin bound to H13 and reversed the inhibitory activity of
      this fragment but did not bind to H10 and H12. We conclude that domain 4a can act
      as an independent inhibitory actin-tropomyosin binding domain, but its properties
      are very different from the extreme C-terminal domain 4b.

PMID- 9601069
TI  - Three different prohormones yield a variety of Hydra-RFamide (Arg-Phe-NH2)
      neuropeptides in Hydra magnipapillata.
AB  - The freshwater polyp Hydra is the most frequently used model for the study of
      development in cnidarians. Recently we isolated four novel Arg-Phe-NH2 (RFamide)
      neuropeptides, the Hydra-RFamides I-IV, from Hydra magnipapillata. Here we
      describe the molecular cloning of three different preprohormones from H.
      magnipapillata, each of which gives rise to a variety of RFamide neuropeptides.
      Preprohormone A contains one copy of unprocessed Hydra-RFamide I (QWLGGRFG), II
      (QWFNGRFG), III/IV [(KP)HLRGRFG] and two putative neuropeptide sequences
      (QLMSGRFG and QLMRGRFG). Preprohormone B has the same general organization as
      preprohormone A, but instead of unprocessed Hydra-RFamide III/IV it contains a
      slightly different neuropeptide sequence [(KP)HYRGRFG]. Preprohormone C contains
      one copy of unprocessed Hydra-RFamide I and seven additional putative
      neuropeptide sequences (with the common N-terminal sequence QWF/LSGRFGL). The two
      Hydra-RFamide II copies (in preprohormones A and B) are preceded by Thr residues,
      and the single Hydra-RFamide III/IV copy (in preprohormone A) is preceded by an
      Asn residue, confirming that cnidarians use unconventional processing signals to
      generate neuropeptides from their precursor proteins. Southern blot analyses
      suggest that preprohormones A and B are each coded for by a single gene, whereas
      one or possibly two closely related genes code for preprohormone C. Northern blot
      analyses and in situ hybridizations show that the gene coding for preprohormone A
      is expressed in neurons of both the head and foot regions of Hydra, whereas the
      genes coding for preprohormones B and C are specifically expressed in neurons of
      different regions of the head. All of this shows that neuropeptide biosynthesis
      in the primitive metazoan Hydra is already rather complex.

PMID- 9601070
TI  - Electron donation to the flavoprotein NifL, a redox-sensing transcriptional
      regulator.
AB  - Transcriptional control of the nitrogen fixation (nif) genes in response to
      oxygen in Azotobacter vinelandii is mediated by nitrogen fixation regulatory
      protein L (NifL), a regulatory flavoprotein that modulates the activity of the
      transcriptional activator nitrogen fixation regulatory protein A (NifA). CD
      spectra of purified NifL indicate that FAD is bound to NifL in an asymmetric
      environment and the protein is predominantly alpha-helical. The redox potential
      of NifL is -226 mV at pH 8 as determined by the enzymic reduction of NifL by
      xanthine oxidase/xanthine in the presence of appropriate mediators. The reduction
      of NifL by xanthine oxidase prevented NifL from acting as an inhibitor of NifA.
      In the absence of electron mediators NifL could also be reduced by Escherichia
      coli flavohaemoprotein (Hmp) with NADH as reductant. Hmp contains a globin-like
      domain with haem B as prosthetic group and an FAD-containing oxidoreductase
      module. The carboxyferrohaem form of Hmp was competent to reduce NifL, suggesting
      that electron donation to NifL originates from the flavin in Hmp rather than by
      direct electron transfer from the haem. Spinach ferredoxin:NAD(P) oxidoreductase,
      which adopts a folding similar to the FAD- and NAD-binding domains of Hmp, also
      reduced NifL with NADH as reductant. Re-oxidation of NifL occurs rapidly in the
      presence of air, raising the possibility that NifL might sense intracellular
      oxygen. We propose a physiological redox cycle in which the oxidation of NifL by
      oxygen and hence the activation of its inhibitory properties occurs rapidly, in
      contrast with the switch from the active to the reduced form of NifL, which
      occurs more slowly.

PMID- 9601071
TI  - Uptake and metabolic fate of [HisA8,HisB4,GluB10,HisB27]insulin in rat liver in
      vivo.
AB  - Receptor-mediated endocytosis and subsequent endosomal proteolysis of
      [125I]TyrA14-[HisA8,HisB4,GluB10,HisB27]in sulin ([125I]TyrA14-H2 analogue), an
      insulin analogue exhibiting a high affinity for the insulin receptor, has been
      studied in liver parenchymal cells by quantitative subcellular fractionation and
      compared with that of wild-type [125I]TyrA14-insulin. Whereas the kinetics of
      uptake of the H2 analogue by liver was not different from that of insulin, the H2
      analogue radioactivity after the 2 min peak declined significantly more slowly. A
      significant retention of the H2 analogue compared with insulin in both plasma
      membrane and endosomal fractions was observed and corresponded to decreased
      processing and dissociation of the H2 analogue. Cell-free endosomes preloaded in
      vivo with radiolabelled ligands and incubated in vitro processed insulin and
      extraluminally released insulin intermediates at a 2-3-fold higher rate than the
      H2 analogue. In vitro proteolysis of both non-radiolabelled and monoiodinated
      molecules by endosomal lysates showed a decreased response to the endosomal
      proteolytic machinery for the H2 analogue. However, in cross-linking and
      competition studies the H2 analogue exhibited an affinity for insulin-degrading
      enzyme identical with that of wild-type insulin. Brij-35-permeabilized endosomes
      revealed a 2-fold higher rate of dissociation of insulin from internalized
      receptors compared with the H2 analogue. After the administration of a saturating
      dose of both ligands, a rapid and reversible ligand-induced translocation of
      insulin receptor was observed, but without receptor loss. The H2 analogue induced
      a higher receptor concentration and tyrosine autophosphorylation of the receptor
      beta subunit in endosomes. Moreover, a prolonged temporal interaction of the in
      vivo injected H2 analogue with receptor was observed by direct binding assays
      performed on freshly prepared subcellular fractions. These results indicate that
      endosomal proteolysis for the H2 analogue is slowed as a result of an increased
      residence time of the analogue on the insulin receptor and a low affinity of
      endosomal acidic insulinase for the dissociated H2 molecule.

PMID- 9601072
TI  - Intermediates in the catalytic cycle of lentil (Lens esculenta) seedling copper
      containing amine oxidase.
AB  - Spectrophotometry and rapid-scanning stopped-flow spectroscopy have been used to
      investigate the visible absorbance changes that occur in the course of the
      reduction of lentil (Lens esculenta) seedling amine oxidase by substrate. The
      catalytic cycle of the enzyme employs several intermediates but, owing to kinetic
      limitations, some of them were not identified in previous studies. In this study
      we have examined several substrates, either rapidly reacting (e.g. putrescine) or
      slowly reacting (e.g. gamma-aminobutanoic acid). Two forms of the enzyme, namely
      the Cu(I)-aminoresorcinol and quinone ketimine derivatives, whose
      characterization was elusive in previous studies, have been identified and
      assigned an optical spectrum. Moreover the reduced form of the enzyme is shown to
      be an equilibrium mixture of two species, the Cu(I)-semiquinolamine radical and
      Cu(II)-aminoresorcinol; these have been resolved by pH dependence and assigned
      spectra as well as a second-order rate constant for the reaction with oxygen.
      Thus the results presented here identify all the catalytic intermediates
      suggested by the chemical nature of the coenzyme and define their spectroscopic
      and reactivity properties.

PMID- 9601073
TI  - N epsilon,N epsilon-dimethyl-lysine cytochrome c as an NMR probe for lysine
      involvement in protein-protein complex formation.
AB  - The reductively dimethylated derivatives of horse and yeast iso-1
      ferricytochromes c have been prepared and characterized for use as NMR probes of
      the complexes formed by cytochrome c with bovine liver cytochrome b5 and yeast
      cytochrome c peroxidase. The electrostatic properties and structures of the
      derivatized cytochromes are not significantly perturbed by the modifications;
      neither are the electrostatics of protein-protein complex formation or rates of
      interprotein electron transfer. Two-dimensional 1H-13C NMR spectroscopy of the
      complexes formed by the derivatized cytochromes with cytochrome b5 and cytochrome
      c peroxidase has been used to investigate the number and identity of lysine
      residues of cytochrome c that are involved in interprotein interactions of
      cytochrome c. The NMR data are incompatible with simple static models proposed
      previously for the complexes formed by these proteins, but are consistent with
      the presence of multiple, interconverting complexes of comparable stability,
      consistent with studies employing Brownian dynamics to model the complexes. The
      NMR characteristics of the Nepsilon,Nepsilon-dimethyl-lysine groups, their
      chemical shift dispersion, oxidation state and temperature dependences and the
      possibility of chemical exchange phenomena are discussed with relevance to the
      utility of Nepsilon, Nepsilon-dimethyl-lysine's being a generally useful
      derivative for characterizing protein-protein complexes.

PMID- 9601074
TI  - Direct observation of lipoprotein cholesterol ester degradation in lysosomes.
AB  - We have investigated whether pyrene-labelled cholesterol esters (PyrnCEs) (n
      indicates the number of aliphatic carbons in the pyrene-chain) can be used to
      observe the degradation of low-density lipoprotein (LDL)-derived cholesterol
      esters (CEs) in the lysosomes of living cells. To select the optimal substrates,
      hydrolysis of the PyrnCE species by lysosomal acid lipase (LAL) in
      detergent/phospholipid micelles was compared. The rate of hydrolysis varied
      markedly depending on the length of the pyrenyl chain. Pyr10CE was clearly the
      best substrate, while Pyr4CE was practically unhydrolysed. Pyr10CE and
      [3H]cholesteryl linoleate, the major CE species in LDL, were hydrolysed equally
      by LAL when incorporated together into reconstituted LDL (rLDL) particles, thus
      indicating that Pyr10CE is a reliable reporter of the lysosomal degradation of
      native CEs. When rLDL particles containing Pyr4CE or Pyr10CE were incubated with
      fibroblasts, the accumulation of bright intracellular vesicular fluorescence was
      observed with the former fluorescent derivative, but not with the latter.
      However, when the cells were treated with chloroquine, an inhibitor of lysosomal
      hydrolysis, or when cells with defective LAL were employed, Pyr10CE also
      accumulated in vesicular structures. HPLC analysis of cellular lipid extracts
      fully supported these imaging results. It is concluded that PyrnCEs can be used
      to observe degradation of CEs directly in living cells. This should be
      particularly useful when exploring the mechanisms responsible for the
      accumulation of lipoprotein-derived CEs in complex systems such as the arterial
      intima.

PMID- 9601075
TI  - Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs)
      by the G-protein-coupled receptor agonist phenylephrine in the perfused rat
      heart.
AB  - We investigated the ability of phenylephrine (PE), an alpha-adrenergic agonist
      and promoter of hypertrophic growth in the ventricular myocyte, to activate the
      three best-characterized mitogen-activated protein kinase (MAPK) subfamilies,
      namely p38-MAPKs, SAPKs/JNKs (i.e. stress-activated protein kinases/c-Jun N
      terminal kinases) and ERKs (extracellularly responsive kinases), in perfused
      contracting rat hearts. Perfusion of hearts with 100 microM PE caused a rapid
      (maximal at 10 min) 12-fold activation of two p38-MAPK isoforms, as measured by
      subsequent phosphorylation of a p38-MAPK substrate, recombinant MAPK-activated
      protein kinase 2 (MAPKAPK2). This activation coincided with phosphorylation of
      p38-MAPK. Endogenous MAPKAPK2 was activated 4-5-fold in these perfusions and this
      was inhibited completely by the p38-MAPK inhibitor, SB203580 (10 microM).
      Activation of p38-MAPK and MAPKAPK2 was also detected in non-contracting hearts
      perfused with PE, indicating that the effects were not dependent on the positive
      inotropic/chronotropic properties of the agonist. Although SAPKs/JNKs were also
      rapidly activated, the activation (2-3-fold) was less than that of p38-MAPK. The
      ERKs were activated by perfusion with PE and the activation was at least 50% of
      that seen with 1 microM PMA, the most powerful activator of the ERKs yet
      identified in cardiac myocytes. These results indicate that, in addition to the
      ERKs, two MAPK subfamilies, whose activation is more usually associated with
      cellular stresses, are activated by the Gq/11-protein-coupled receptor (Gq/11PCR)
      agonist, PE, in whole hearts. These data indicate that Gq/11PCR agonists activate
      multiple MAPK signalling pathways in the heart, all of which may contribute to
      the overall response (e.g. the development of the hypertrophic phenotype).

PMID- 9601076
TI  - Identification of glycinin in vivo as a polyamine-conjugated protein via a gamma
      glutamyl linkage.
AB  - To identify a polyamine-conjugated protein by the action of transglutaminase in
      the absence of radiolabelled polyamine, extracts prepared from the leaves and
      developing soybean seeds were investigated for the specific activity of
      transglutaminase and the content of free polyamines. We identified the major
      storage protein, glycinin, as a polyamine-conjugated protein. This was
      established by the following procedures: (1) immunolocalization with antibody
      against putrescine prepared in rabbit against putrescine-BSA conjugate; (2)
      immunocross-reactivity on nitrocellulose transblot of the purified glycinin
      subunits by using antibody against putrescine; (3) identification of polyamines
      in acid hydrolysates of purified glycinin; (4) release of polyamines in
      proteolytic digests through the catalytic action of gamma-glutamylamine
      cyclotransferase, an enzyme specific for the disassembly of gamma-glutamylamines.
      The activity of gamma-glutamylamine cyclotransferase was also identified in
      soybean seeds.

PMID- 9601077
TI  - Cadmium-induced differential accumulation of metallothionein isoforms in the
      Antarctic icefish, which exhibits no basal metallothionein protein but high
      endogenous mRNA levels.
AB  - Reverse transcriptase-mediated PCR has been used to isolate two distinct
      metallothionein (MT) cDNA species from RNA extracted from icefish liver, namely
      MT-I and MT-II. Northern blot analysis with these cDNA species revealed that
      significant endogenous levels of MT mRNA were present in liver tissues of normal
      animals despite the fact that no MT protein could be found accumulating in the
      same tissue. However, multiple injections of CdCl2 induced high levels of both MT
      mRNA and MT protein. Sequence analysis of the cDNA species that were present
      after cadmium injection revealed the presence of both isoforms. Quantification of
      the MT-I and MT-II transcripts from normal and heavy-metal-treated fish showed an
      alteration in the ratio of the MT isoform transcripts. Endogenous transcripts
      consisted mostly of MT-II, whereas the MT-I transcript was preferentially
      accumulated only in response to the cadmium salt. The protein encoded by each
      cDNA isoform was isolated from the heavy-metal-treated fish and the availability
      of the specific MT mRNA for translation was demonstrated by translation in vitro.
      These results show that: (1) there is a discrepancy between the significant
      endogenous levels of MT mRNA and the absence of MT protein; (2) the accumulation
      of MT in icefish liver can be triggered by heavy metals; (3) genes encoding
      distinct MT isoforms are differentially regulated by heavy metals.

PMID- 9601078
TI  - Translated anti-sense product of the Na/phosphate co-transporter (NaPi-II).
AB  - The homeostasis of Pi in marine teleosts is maintained by renal Pi secretion as
      well as by Pi reabsorption. A Na/Pi co-transport system belonging to the NaPi-II
      protein family is instrumental in tightly controlled renal Pi handling in mammals
      and fish. We have isolated an NaPi-II related cDNA from winter flounder. It was
      cloned from a female gonad cDNA library and is 624 bp long. The transcript is
      expressed in female and male flounder gonads as well as in kidney and intestine,
      although at very low levels. RNase H digestion experiments revealed an opposite
      orientation of the transcript with regard to NaPi-II-related mRNA. The anti-sense
      orientation was confirmed by genomic sequence analysis and Southern blotting.
      Alluding to the sense transcript, the anti-sense transcript was denoted IPAN. The
      open reading frame of IPAN encodes a basic protein of 68 amino acid residues.
      Immunohistochemistry confined the anti-sense related protein, Ipan, to a
      submembranous compartment of immature oocytes, suggesting a role in oocyte
      development. In kidney and intestine Ipan is partly co-localized with the Na/Pi
      co-transporter, implying a regulatory function for the anti-sense protein.
      However, direct protein-protein interaction could not be established. The
      existence of a putative open reading frame in other species extends the
      biological significance of the novel protein.

PMID- 9601079
TI  - BeWo choriocarcinoma cells produce laminin 10.
AB  - BeWo is a choriocarcinoma cell line that generates an extracellular matrix (ECM)
      rich in laminin and is a useful model for human trophoblast. Immunofluorescence
      with monoclonal antibodies demonstrates that BeWo ECM contains laminin subunits
      beta1 and gamma1. Immunoprecipitation from conditioned medium shows that the
      cells secrete two distinct laminin trimers both containing beta1 and gamma1 but
      with alpha subunits of approx. 400 and 450 kDa. The culture medium also contains
      a species thought to be beta1 gamma1 dimer. Immunoprecipitation with monoclonal
      antibody 4C7, previously thought to recognize the alpha1 subunit, isolates
      complexes containing only the smaller alpha subunit. A second complex containing
      the larger alpha subunit along with beta1, gamma1 and a 150 kDa polypeptide is
      precipitated from 4C7-depleted medium with an anti-(laminin 1) polyclonal
      antibody. Peptide sequencing demonstrates that the 4C7-reactive species is
      alpha5, which is present as two similarly sized polypeptides. mRNA species
      encoding laminin subunits alpha1, alpha5, beta1, beta2 and gamma1 are all present
      in the cells. These results demonstrate the secretion of a novel laminin isoform,
      laminin 10, the subunit composition of which is alpha5 beta1 gamma1. Laminin 1 is
      also produced. No evidence for the secretion of beta2-containing laminin isoforms
      could be derived despite the presence of beta2 mRNA. Analysis with reverse
      transcriptase-mediated PCR also showed the presence of laminin alpha5 in first
      trimester placenta and decidua.

PMID- 9601080
TI  - Quantification of cathepsins B and L in cells.
AB  - A method for quantifying active cysteine proteinases in mammalian cells has been
      developed using an active-site-directed inhibitor. Fluoren-9-ylmethoxycarbonyl(di
      iodotyrosylalanyl)-diaz omethane (Fmoc-[I2]Tyr-Ala-CHN2) was prepared and shown
      to react irreversibly with cathepsins B and L, but not with cathepsin S. The non-
      and mono-iodo forms of the inhibitor reacted with all three enzymes. These
      results demonstrate that, unlike cathepsins B and L, cathepsin S has a restricted
      S2-binding site that cannot accommodate the bulky di-iodotyrosine. Fmoc-[I2]Tyr
      Ala-CHN2 was able to penetrate cells and react with active enzymes within the
      cells. A radiolabelled form of the inhibitor was synthesized and the
      concentration of functional inhibitor was established by titration with papain.
      This inhibitor was used to quantify active cysteine proteinases in cultured
      cells. Active cathepsin B was found to be expressed by all of the cells studied,
      consistently with a housekeeping role for this enzyme. Active forms of cathepsin
      L were also expressed by all of the cells, but in different quantities. Two
      additional proteins were labelled in some of the cells, and these may represent
      other non-characterized proteinases. Higher levels of active cathepsins B and L,
      and an unidentified protein of Mr 39000, were found in breast tumour cells that
      are invasive, compared with those that are not invasive. From the data obtained,
      it can be calculated that the concentrations of both active cathepsins B and L in
      lysosomes can be as high as 1 mM, each constituting up to 20% of total protein in
      the organelle. This new technique provides a more direct procedure for
      determining the proteolytic potential of cellular lysosomes.

PMID- 9601081
TI  - Oxidative scission of plant cell wall polysaccharides by ascorbate-induced
      hydroxyl radicals.
AB  - Scission of plant cell wall polysaccharides in vivo has generally been assumed to
      be enzymic. However, in the presence of l-ascorbate, such polysaccharides are
      shown to undergo non-enzymic scission under physiologically relevant conditions.
      Scission of xyloglucan by 1 mM ascorbate had a pH optimum of 4.5, and the maximum
      scission rate was reached after a 10-25-min delay. Catalase prevented the
      scission, whereas added H2O2 (0.1-10 mM) increased the scission rate and
      shortened the delay. Ascorbate caused detectable xyloglucan scission above
      approx. 5 microM. Dehydroascorbate was much less effective. Added Cu2+ (>0.3
      microM) also increased the rate of ascorbate-induced scission; EDTA was
      inhibitory. The rate of scission in the absence of added metals appeared to be
      attributable to the traces of Cu (2.8 mg.kg-1) present in the xyloglucan.
      Ascorbate-induced scission of xyloglucan was inhibited by radical scavengers;
      their effectiveness was proportional to their rate constants for reaction with
      hydroxyl radicals (.OH). It is proposed that ascorbate non-enzymically reduces O2
      to H2O2, and Cu2+ to Cu+, and that H2O2 and Cu+ react to form .OH, which causes
      oxidative scission of polysaccharide chains. Evidence is reviewed to suggest
      that, in the wall of a living plant cell, Cu+ and H2O2 are formed by reactions
      involving ascorbate and its products, dehydroascorbate and oxalate. Systems may
      thus be in place to produce apoplastic .OH radicals in vivo. Although .OH
      radicals are often regarded as detrimental, they are so short-lived that they
      could act as site-specific oxidants targeted to play a useful role in loosening
      the cell wall, e.g. during cell expansion, fruit ripening and organ abscission.

PMID- 9601082
TI  - Resistance to the apoptotic effect of aggregated amyloid-beta peptide in several
      different cell types including neuronal- and hepatoma-derived cell lines.
AB  - There is a large body of literature indicating that aggregated amyloid-beta
      peptide (Abeta) is toxic to neurons and suggesting that this neurotoxicity
      represents the final common pathway for neuronal degeneration in Alzheimer's
      disease. Previous studies have shown the outgrowth of a subclone of the rat
      neuronal cell line PC12 that is resistant to the toxic effect of aggregated Abeta
      peptide if the parent cell line is grown in the presence of aggregated Abeta
      peptide for a number of passages [Behl, Davis, Lesley and Schubert (1994) Cell
      77, 817-827; Boland, Behrens, Choi, Manias and Perlmutter (1996) J. Biol. Chem.
      271, 18032-18044]. To begin to characterize the mechanism by which PC12 cells
      become resistant to the apoptotic effect of Abeta peptide, in the present study
      we examined whether the resistance was specific to aggregated peptides, specific
      to an apoptotic form of cell death, and specific in cell type or was a general
      resistance to cell death that could be elicited in diverse cell types. The
      results show that the resistance is specific to compounds that have apoptotic
      effects through the generation of hydroxyl radical or H2O2, including aggregated
      Abeta-(25-35), Abeta-(1-40), Abeta-(1-42), Abeta-(1-43), amylin, 6
      hydroxydopamine and H2O2 itself. The resistant subclones of PC12 were not
      resistant to other forms of apoptotic cell death or to necrotic cell death. The
      resistant state was also identified in a human hepatoma cell line, HepG2, when it
      was grown in the presence of aggregated Abeta-(25-35) for several passages,
      indicating that the mechanism(s) or molecule(s) responsible for this resistance
      are not restricted to neuronal cells and may be relevant to the pathobiology of
      oxidative injury in other cell types.

PMID- 9601083
TI  - Characterization of sphingosine kinase (SK) activity in Saccharomyces cerevisiae
      and isolation of SK-deficient mutants.
AB  - Sphingosine kinase (SK) catalyses the phosphorylation of sphingosine to generate
      sphingosine 1-phosphate, which is a second messenger involved in the
      proliferative responses of mammalian cells. Although the yeast Saccharomyces
      cerevisiae has similar phosphorylated sphingoid bases which appear to be involved
      in growth regulation and the response to stress, SK activity had not been
      previously demonstrated in yeast. In this study, an in vitro system was set up to
      characterize yeast SK activity. Activity was detected in the cytosol at neutral
      pH and 37 degreesC. Yeast SK phosphorylated the sphingoid bases sphingosine,
      dihydrosphingosine and phytosphingosine. (d,l)-threo-dihydrosphingosine, an
      inhibitor of mammalian SK, did not inhibit the yeast enzyme. Unique properties of
      yeast SK were an optimal temperature of 43 degreesC, and in vivo activation
      during nutrient deprivation. Spontaneous mutants with diminished SK activity were
      isolated utilizing a screen for resistance to sphingosine in a sphingosine
      phosphate-lyase deletion background. Abnormal growth and heat sensitivity were
      observed in these mutants. These findings suggest that SK may function as a
      stress-response protein in yeast.

PMID- 9601084
TI  - Hormonal regulation of focal adhesions in bovine adrenocortical cells: induction
      of paxillin dephosphorylation by adrenocorticotropic hormone.
AB  - A study of bovine adrenocortical cell shape on adrenocorticotropic hormone (ACTH)
      challenge showed that the cells round up and develop arborized processes. This
      effect was found to be (1) specific for ACTH because angiotensin II and basic
      fibroblast growth factor have no effect; (2) mediated by a cAMP-dependent pathway
      because forskolin reproduces the effect of the hormone; (3) inhibited by sodium
      orthovanadate, a phosphotyrosine phosphatase inhibitor, but unchanged by okadaic
      acid, a serine/threonine phosphatase inhibitor; and (4) correlated with a
      complete loss of focal adhesions. Biochemical studies of the focal-adhesion
      associated proteins showed that pp125fak, vinculin (110 kDa) and paxillin (70
      kDa) were detected in the Triton X-100-insoluble fraction from adrenocortical
      cells. During cell adhesion on fibronectin as substratum, two major
      phosphotyrosine-containing proteins of molecular masses 125 and 68 kDa were
      immunodetected in the same fraction. A dramatic decrease in the extent of
      tyrosine phosphorylation of these proteins was observed within 60 min after
      treatment with ACTH. No change in pp125fak tyrosine phosphorylation nor in Src
      activity was detected. In contrast, paxillin was found to be tyrosine
      dephosphorylated in a time-dependent manner in ACTH-treated cells. Sodium
      orthovanadate completely prevented the effect of ACTH. These observations suggest
      a possible role for phosphotyrosine phosphatases in hormone-dependent cellular
      regulatory processes.

PMID- 9601085
TI  - Fatty acids induce release of Ca2+ from acidosomal stores and activate
      capacitative Ca2+ entry in Dictyostelium discoideum.
AB  - cAMP-induced Ca2+ fluxes in Dictyostelium discoideum largely depend on
      phospholipase A2 activity generating non-esterified fatty acids [Schaloske and
      Malchow (1997) Biochem. J. 327, 233-238]. In the present study the effect of
      fatty acids on Ca2+ homoeostasis in D. discoideum was investigated. Cytosolic
      free Ca2+ concentration ([Ca2+]i) was analysed by digital imaging of single fura2
      dextran-loaded cells. Arachidonic acid and linoleic acid induced a transient
      increase in [Ca2+]i. The concentration of arachidonic acid determined the
      percentage of responding cells, with the mean height of the increase being dose
      independent. In nominally Ca2+-free medium or in the presence of bis-(o
      aminophenoxy)ethane-N, N,N',N'-tetra-acetic acid (BAPTA), no [Ca2+]i transient
      was detectable. In spite of this, we found that (1) arachidonic acid induced Ca2+
      release from permeabilized cells and from vesicular fractions at concentrations
      that elicited Ca2+ influx in intact cells and (2) Ca2+ entry was inhibited by
      inhibitors of Ca2+-transport ATPases and V-type H+-ATPase, indicating that
      intracellular Ca2+ release precedes Ca2+ entry. Inhibition studies and mutant
      analysis point to the acidosomal Ca2+ stores as a target of fatty acids. Although
      fatty acids can substitute fully for cAMP with respect to Ca2+ influx in wild
      type cells, experiments with a mutant strain revealed that cAMP also sensitizes
      the Ca2+-entry mechanism: cAMP-induced Ca2+ influx was normal in a phospholipase
      C knockout mutant but influx was fairly insensitive to arachidonic acid in this
      strain. This defect could be overcome by higher doses of arachidonic acid which
      cause sufficient Ca2+ to be released from the stores to trigger extracellular
      Ca2+ entry.

PMID- 9601086
TI  - Structure and topography of the membrane-binding C2 domain of factor VIII in the
      presence of dodecylphosphocholine micelles.
AB  - A 21 residue peptide from the C2 domain of the antihaemophilic factor VIII
      competes with factor VIII for membrane-binding sites in vitro. Here, we provide
      the structure and topography of the peptide in solution, on dodecylphosphocholine
      (DPC) micelles, determined using 1H-NMR spectroscopy. The peptide assumes an
      amphipathic structure comprising an extended N-terminal region and a C-terminal
      helix. The average root-mean-square deviation is 0.7+/-0.2 A for the
      superimposition of the backbone atoms of Ile6 to Arg18 on the lowest energy
      structure. Whereas the backbone conformation is similar to that in SDS micelles,
      the Trp11 side-chain orientation is dramatically changed. The indole ring is
      nearly parallel to the peptide backbone in SDS micelles but perpendicular in DPC
      micelles. Further, pKa values of the two histidines change by more than 1 pH unit
      in SDS relative to DPC, which localizes the imidazole rings to the interfacial
      region. Line-broadening induced by spin-labelled phosphatidylcholine shows that
      most of the amino acid side-chains that penetrate the DPC micelle are
      hydrophobic. Thus, the long axis of the peptide lies parallel to the micelle
      surface and the hydrophobic face of the alpha-helix provides hydrophobic membrane
      interaction. The large chemical shift changes shown by Trp11 and N-terminal amino
      acid residues in SDS relative to DPC indicate that this region may be involved in
      membrane phospholipid recognition. 1H-NMR assignments, CD spectra, one
      dimensional 1H-NMR spectra, chemical-shift analysis and nuclear Overhauser effect
      information are reported in Supplementary Publication SUP 50184 (11 pages), which
      has been deposited at the British Library Document Supply Centre, Boston Spa,
      Wetherby, West Yorkshire LS23 7BQ, U.K, from whom copies can be obtained
      according to the terms indicated in Biochem. J. (1997) 321, 8.

PMID- 9601087
TI  - Purification and characterization of a 100 kDa DNA polymerase from cauliflower
      inflorescence.
AB  - A DNA polymerase from cauliflower (Brassica oleracea var. botrytis) inflorescence
      has been purified to near homogeneity through five successive column
      chromatographies, and temporally designated cauliflower polymerase 1. Cauliflower
      polymerase 1 is a monopolypeptide with a molecular mass of 100 kDa. The enzyme
      efficiently uses synthetic DNA homopolymers and moderately activated DNA and a
      synthetic RNA homopolymer as template-primers. The enzyme is strongly sensitive
      to dideoxythymidine triphosphate and N-ethylmaleimide, but it is insensitive to
      aphidicolin. It was stimulated with 250 mM KCl. Its mode of DNA synthesis is high
      processive with or without proliferating-cell nuclear antigen. A 3'-->5'
      exonuclease activity is associated with cauliflower polymerase 1. The enzyme is
      clearly different from cauliflower mitochondrial polymerase and does not resemble
      the four different types of wheat DNA polymerase, designated wheat DNA
      polymerases A, B, CI and CII. In the present paper the role of the enzyme in
      plant DNA synthesis is discussed.

PMID- 9601088
TI  - Two oligopeptide transporters from Caenorhabditis elegans: molecular cloning and
      functional expression.
AB  - Two novel oligopeptide transporter cDNA clones, CPTA and CPTB, were identified by
      screening a Caenorhabditis elegans cDNA library using homology hybridization. The
      transporter proteins deduced from the cDNAs possess multiple transmembrane
      domains and reveal a moderate similarity to their mammalian counterparts in amino
      acid sequences. CPTA and CPTB, when expressed in Xenopus laevis oocytes and
      studied by both radiotracer flux and microelectrode voltage-clamp protocol,
      displayed a saturable electrogenic transport activity driven by a proton gradient
      with an overlapping broad spectrum of substrate specificity. Both transporters
      recognize di-, tri- and tetra-peptides including
      phenylalanylmethionylarginylphenylalaninamide (FMRFamide) and N
      acetylaspartylglutamate, members of a large neuropeptide family commonly found
      throughout the animal kingdom. Kinetic analysis, however, revealed that CPTA and
      CPTB differed in their affinity for the peptide substrates, the former being a
      high-affinity type and the latter a low-affinity type. CPTA and CPTB are encoded
      by two distinct genes localized on separate chromosomes and are expressed during
      the whole life span of the organism.

PMID- 9601091
TI  - The fission yeast microtubule cytoskeleton.
AB  - The Schizosaccharomyces pombe genome sequencing project (http://www.
      sanger.ac.uk/Projects/S_pombe/) is nearly complete, and this is likely to
      generate interest in fission yeast as a model system beyond its traditional
      strongholds in the study of the cell cycle and sexual differentiation. In many
      fields S. pombe will offer a useful complement to the more widely studied
      Saccharomyces cerevisiae, but in some areas the impact of S. pombe may well rival
      or exceed that of this budding yeast in terms of relevance to higher systems.
      Because of the considerable differences from the S. cerevisiae microtubule
      cytoskeleton, studying microtubules in S. pombe is likely to enhance the
      contribution of model systems to our understanding of the principles and
      practices of microtubule organisation in eukaryotes in general.

PMID- 9601090
TI  - Functional expression in yeast and characterization of a clofibrate-inducible
      plant cytochrome P-450 (CYP94A1) involved in cutin monomers synthesis.
AB  - The chemical tagging of a cytochrome P-450-dependent lauric acid omega
      hydroxylase from clofibrate-treated Vicia sativa seedlings with [1-14C]11
      dodecynoic acid allowed the isolation of a full-length cDNA designated CYP94A1.
      We describe here the functional expression of this novel P-450 in two
      Saccharomyces cerevisiae strains overproducing their own NADPH-cytochrome P-450
      reductase or a reductase from Arabidopsis thaliana. The results show a much
      higher efficiency of the yeast strain overproducing the plant reductase compared
      with the yeast strain overproducing its own reductase for expressing CYP94A1. The
      methyl end of saturated (from C-10 to C-16) and unsaturated (C18:1, C18:2 and
      C18:3) fatty acids was mainly oxidized by CYP94A1. Both E/Z and Z/E
      configurations of 9, 12-octadecadienoic acids were omega-hydroxylated. Lauric,
      myristic and linolenic acids were oxidized with the highest turnover rate (24 min
      1). The strong regioselectivity of CYP94A1 was clearly shifted with sulphur
      containing substrates, since both 9- and 11-thia laurate analogues were
      sulphoxidized. Similar to animal omega-hydroxylases, this plant enzyme was
      strongly induced by clofibrate treatment. Rapid CYP94A1 transcript accumulation
      was detected less than 20 min after exposure of seedlings to the hypolipidaemic
      drug. The involvement of CYP94A1 in the synthesis of cutin monomers and fatty
      acid detoxification is discussed.

PMID- 9601089
TI  - Regulation of the human protein C inhibitor gene expression in HepG2 cells: role
      of Sp1 and AP2.
AB  - Protein C inhibitor (PCI) is the plasma inhibitor of activated protein C, which
      is the main protease of the anticoagulant protein C pathway. In this study the
      transcriptional regulation of human PCI gene in the human hepatoma cell line,
      HepG2, was characterized by evaluating the transient expression of a luciferase
      reporter gene. The 5' flanking region (residues -1587 to +2) of the PCI gene
      showed an adequate transcriptional activity, the maximum transcriptional activity
      being in a region between residues -452 and -94, which contains an Sp1-binding
      site, two AP2-binding sites and an inverted AP2-binding site. Transient
      expression assays with various deletion mutants and site-directed mutants showed
      that the Sp1-binding site (residues -302 to -294) has a potent promoter activity
      and that the upstream AP2-binding site (residues -350 to -343) has a potent
      enhancer activity; no activity was detected in the inverted (residues -413 to 
      404) and downstream (residues -136 to -127) AP2-binding sites. In addition, a
      region of the PCI gene (residues -452 to -414) containing the STATx-binding site,
      the A-activator (AA)-binding site, and the interferon alpha (IFN-alpha) response
      element, and another region of the PCI gene (residues -176 to -147) containing
      the GATA-1 and the IFN-gamma response element showed potent silencer activities.
      Gel mobility-shift assays with various DNA fragments indicated that the Sp1
      binding site, the upstream AP2-binding site, the AA-binding site and the IFN
      gamma response element interact with nuclear protein(s) of HepG2 cells. These
      findings suggest that the Sp1-binding site is the promoter, the AP2-binding site
      (residues -350 to -343) the enhancer, and both the AA-binding site and the IFN
      gamma response element are the silencers of human PCI gene expression in HepG2
      cells.

PMID- 9601092
TI  - Patterns of free calcium in zebrafish embryos.
AB  - Direct knowledge of Ca2+ patterns in vertebrate development is largely restricted
      to early stages, in which they control fertilization, ooplasmic segregation and
      cleavage. To explore new roles of Ca2+ in vertebrate development, we injected the
      Ca2+ indicator aequorin into zebrafish eggs and imaged Ca2+ throughout the first
      day of development. During early cleavages, a high Ca2+ zone is seen in the
      cleavage furrows. The high Ca2+ zone during first cleavage spreads as a slow wave
      (0.5 microm/second) and is preceded by three Ca2+ pulses within the animal pole
      region of the egg. When Ca2+ concentrations are clamped at the resting level by
      BAPTA buffer injection into the zygote, all signs of development are blocked. In
      later development, Ca2+ patterns are associated with cell movements during
      gastrulation, with neural induction, with brain regionalization, with formation
      of the somites and neural keel, with otic placode formation, with muscle
      movements and with formation of the heart. Particularly remarkable is a sharp
      boundary between high Ca2+ in the presumptive forebrain and midbrain versus low
      Ca2+ in the presumptive hindbrain starting at 10 hours of development. When Ca2+
      changes are damped by injection of low concentrations of BAPTA, fish form with
      greatly reduced eyes and hearts. The present study provides a first overview of
      Ca2+ patterns during prolonged periods of vertebrate development and points to
      new roles of Ca2+ in cellular differentiation and pattern formation.

PMID- 9601093
TI  - Direct cloning and analysis of DNA sequences from a region of the Chinese hamster
      genome associated with aphidicolin-sensitive fragility.
AB  - Fragile sites are reproducibly expressed and chemically induced decondensations
      on mitotic chromosomes observed under cytological conditions. They are classified
      both on the basis of the frequency with which they occur (rare and common) and in
      terms of the chemical agent used to induce expression in tissue culture cells.
      Aphidicolin-sensitive common fragile sites appear to be ubiquitous in humans and
      other mammals and have been considered as candidates of pathological importance.
      Recently DNA from FRA3B, the most highly expressed constitutive fragile site in
      the human genome, has been cloned although as yet the cause of the underlying
      fragility has not been identified. In this study we describe the isolation, using
      a direct cloning approach, of DNA from a region of the Chinese hamster genome
      associated with aphidicolin-inducible fragility. Cells of a human-hamster somatic
      cell hybrid were transfected with a pSV2HPRT vector while exposed to aphidicolin,
      an inhibitor of DNA polymerases alpha, delta and epsilon. FISH analysis of stable
      transfectant clones revealed that the ingoing plasmid DNA had preferentially
      integrated into fragile site-containing chromosomal bands. Plasmid rescue was
      used to recover DNA sequences flanking one such integration site in the hamster
      genome. We demonstrate by FISH analysis of metaphase cells induced with
      aphidicolin that the rescued DNA is from a region of fragility on Chinese hamster
      chromosome 2, distal to the DHFR locus. Analysis of the DNA sequences flanking
      the integration site revealed the overall A+T content of the 3,725 bp region
      sequenced to be 63.3%, with a highly [A].[T]-rich 156 bp region (86.5%) almost
      adjacent to the integration site. Computational analyses have identified strong
      homologies to Saccharomyces cerevisiae autonomous replicating sequences (ARS),
      polypyrimidine tracts, scaffold attachment site consensus sequences and a 24 bp
      consensus sequence highly conserved in eukaryotic replication origins, all of
      which appear to cluster around the [A].[T]-rich sequences. This domain also
      possesses structural characteristics which are common to both prokaryotic and
      eukaryotic origins of replications, in particular an unusually straight
      conformation of low thermal stability flanked either side by highly bent DNA
      segments. Further isolation and characterisation of DNA sequences from common
      fragile sites will facilitate studies into the underlying nature of these
      enigmatic regions of the mammalian genome, leading to a greater understanding of
      chromatin structure.

PMID- 9601094
TI  - Mph1, a member of the Mps1-like family of dual specificity protein kinases, is
      required for the spindle checkpoint in S. pombe.
AB  - The spindle assembly checkpoint pathway is not essential for normal mitosis but
      ensures accurate nuclear division by blocking the metaphase to anaphase
      transition in response to a defective spindle. Here, we report the isolation of a
      new spindle checkpoint gene, mph1 (Mps1p-like pombe homolog), in the fission
      yeast Schizosaccharomyces pombe, that is required for checkpoint activation in
      response to spindle defects. mph1 functions upstream of mad2, a previously
      characterized component of the spindle checkpoint. Overexpression of mph1, like
      overexpression of mad2, mimics activation of the checkpoint and imposes a
      metaphase arrest. mph1 protein shares sequence similarity with Mps1p, a dual
      specificity kinase that functions in the spindle checkpoint of the budding yeast
      Saccharomyces cerevisiae. Complementation analysis demonstrates that mph1 and
      Mps1p are functionally related. They differ in that Mps1p, but not mph1, has an
      additional essential role in spindle pole body duplication. We propose that mph1
      is the MPS1 equivalent in the spindle checkpoint pathway but not in the SPB
      duplication pathway. Overexpression of mad2 does not require mph1 to impose a
      metaphase arrest, which indicates a mechanism of spindle checkpoint activation
      other than mph1/Mps1p kinase-dependent phosphorylation. In the same screen which
      led to the isolation of mad2 and mph1, we also isolated dph1, a cDNA that encodes
      a protein 46% identical to an S. cerevisiae SPB duplication protein, Dsk2p. Our
      initial characterization indicates that S.p. dph1 and S.c. DSK2 are functionally
      similar. Together these results suggest that the budding and fission yeasts share
      common elements for SPB duplication, despite differences in SPB structure and the
      timing of SPB duplication relative to mitotic entry.

PMID- 9601095
TI  - Actin dynamics in living mammalian cells.
AB  - The actin cytoskeleton maintains the cellular architecture and mediates cell
      movements. To explore actin cytoskeletal dynamics, the enhanced green fluorescent
      protein (EGFP) was fused to human &bgr ;-actin. The fusion protein was
      incorporated into actin fibers which became depolymerized upon cytochalasin B
      treatment. This functional EGFP-actin construct enabled observation of the actin
      cytoskeleton in living cells by time lapse fluorescence microscopy. Stable
      expression of the construct was obtained in mammalian cell lines of different
      tissue origins. In stationary cells, actin rich, ring-like structured 'actin
      clouds' were observed in addition to stress fibers. These ruffle-like structures
      were found to be involved in the reorganization of the actin cytoskeleton. In
      migratory cells, EGFP-actin was found in the advancing lamellipodium. Immobile
      actin spots developed in the lamellipodium and thin actin fibers formed parallel
      to the leading edge. Thus EGFP-actin expressed in living cells unveiled
      structures involved in the dynamics of the actin cytoskeleton.

PMID- 9601096
TI  - Ligand-independent role of the beta 4 integrin subunit in the formation of
      hemidesmosomes.
AB  - Recently, we have shown that a region within the beta4 cytoplasmic domain,
      encompassing the second fibronectin type III (FNIII) repeat and the first 27
      amino acids of the connecting segment, is critical for the localization of alpha6
      beta4 in hemidesmosomes. In addition, this region was shown to regulate the
      distribution of HD1/plectin in transfected cells. In order to investigate the
      function of the beta4 extracellular and cytoplasmic domains in the assembly and
      integrity of hemidesmosomes, we have constructed chimeric receptors consisting of
      the extracellular and transmembrane domains of the interleukin 2 receptor (IL2R),
      fused to different parts of the beta4 cytoplasmic domain. These chimeras are
      expressed as single subunits at the plasma membrane. The results show that the
      first and the second FNIII repeat, together with the first part of the connecting
      segment (in total a stretch of 241 amino acids spanning amino acids 1,115 to
      1,356) are both essential and sufficient for the localization of beta4 in pre
      existing hemidesmosomes. Moreover, expression of the IL2R/beta4 chimeric
      constructs in COS-7 and CHO cells, which do not express alpha6 beta4 or the
      bullous pemphigoid (BP) antigens but do express HD1/plectin, revealed that the
      stretch of 241 amino acids is sufficient for inducing the formation of type II
      hemidesmosomes. Expression of the IL2R/beta4 chimeras in a keratinocyte cell line
      derived from a patient lacking beta4 expression, showed that amino acids 1,115 to
      1,356 can also induce the formation of type I hemidesmosomes. We further
      demonstrate that type I and II hemidesmosomes can also be formed upon adhesion of
      alpha6 beta4-expressing cells to fibronectin. These findings establish that the
      beta4 extracellular domain is not essential for the induction of hemidesmosome
      assembly. Moreover, they demonstrate that binding of alpha6 beta4 to ligand, and
      heterodimerization of alpha6 with beta4, are not required for hemidesmosome
      formation. This indicates that the assembly of hemidesmosomes can be regulated
      from within the cell.

PMID- 9601097
TI  - Identification of IHABP, a 95 kDa intracellular hyaluronate binding protein.
AB  - The extracellular matrix component hyaluronan is believed to play important roles
      in various processes of organogenesis, cell migration and cancer. Recognition of
      and binding to hyaluronan is mediated by cell surface receptors. Three of them,
      CD44, ICAM-1 and RHAMM (receptor for hyaluronic acid mediated motility), have
      been identified. A cDNA clone designated RHAMM turned out to possess transforming
      capacity. Based on this published sequence, we isolated the complete cDNA of the
      murine gene. The cDNA comprises an open reading frame of 2.3 kb and encodes a 95
      kDa protein. The protein carries a hyaluronan binding motif which binds to
      hyaluronan in vitro but not to heparin or chondroitin sulphate. It is
      ubiquitously expressed in normal cells and in all tumour cell lines irrespective
      of their metastatic properties. One tumour cell line, the metastatic Lewis lung
      carcinoma, expresses a larger 105 kDa variant form of the protein due to a
      genomic rearrangement. Antibodies raised against the 95 kDa protein were used for
      subcellular localization studies. The hyaluronan binding protein is not
      detectable at the cell surface but is rather localized exclusively
      intracellularly. Clearly, the sequence we have identified encodes a protein with
      properties substantially different to the RHAMM protein. We tentatively name the
      protein intracellular hyaluronic acid binding protein, IHABP.

PMID- 9601098
TI  - The human hyaluronan receptor RHAMM is expressed as an intracellular protein in
      breast cancer cells.
AB  - The receptor for hyaluronan mediated motility (RHAMM) has been reported to
      mediate migration, transformation, and metastatic spread of murine fibroblasts.
      Here we describe the expression of two human RHAMM isoforms, which are generated
      by alternative splicing of the primary gene transcript, by a series of human
      breast carcinoma cell lines. A polyclonal antibody, raised against a bacterially
      expressed RHAMM fusion protein, detected an 85-90 kDa protein by western blot
      analysis. No correlation between the level of RHAMM mRNA and protein expression
      with known metastatic/malignant potential of the tumour cell lines was observed.
      Interestingly, we found that the antibody did not stain the cell surface but the
      cytoplasm of breast cancer cells. The intracellular localisation of RHAMM was
      confirmed by subcellular fractionation studies. RHAMM proteins were capable of
      binding to hyaluronan, but not to heparin or chondroitin sulphate, in an vitro
      binding assay. We also provide evidence that a potential hyaluronan-binding motif
      in the N terminus of the protein is not involved in the interaction of RHAMM with
      hyaluronan. Our findings lead us to conclude that RHAMM does not function as a
      conventional motility receptor for HA in human breast cancer cells and we suggest
      the term RHAMM be substituted by 'intracellular hyaluronic acid binding protein'
      (IHABP).

PMID- 9601099
TI  - Disruption of the actin cytoskeleton of mammalian cells by the capping complex
      actin-fragmin is inhibited by actin phosphorylation and regulated by Ca2+ ions.
AB  - Fragmin from Physarum polycephalum is a gelsolin-like actin-binding protein and
      interferes with the growth of actin filaments in vitro by severing actin
      filaments and capping their barbed ends through formation of an actin-fragmin
      dimer in a Ca2+-dependent manner. The actin-fragmin dimer is phosphorylated in
      vivo and in vitro on the actin subunit by the actin-fragmin kinase. We have
      studied the properties of these capping proteins and their regulation by actin
      phosphorylation and Ca2+ ions in living PtK2, CV1 and NIH3T3 cultured cells by
      microinjection or by expression in conjunction with immunostaining and
      fluorescence microscopy. Microinjection of the actin-fragmin dimer disintegrated
      the actin cytoskeleton and altered cell morphology. This in vivo effect could be
      blocked by phosphorylation of the actin subunit by the actin-fragmin kinase in
      low Ca2+ conditions, and the capping activity could be recovered by high Ca2+
      concentration, probably through activation of the second actin-binding site in
      fragmin. This suggests that in Physarum microplasmodia, actin polymerization can
      be controlled in a Ca2+-dependent manner through the phosphorylation of actin.
      Microinjected or overexpressed recombinant fragmin did not affect the actin-based
      cytoskeleton or cell morphology of resting cells, unless the cytosolic free Ca2+
      concentration was increased by microinjection of a Ca2+-containing buffer. The
      cells were able to revert to their normal phenotype which indicates that
      endogenous regulatory mechanisms counteracted fragmin activity, probably by
      uncapping fragmin from the barbed ends of filaments. Fragmin also antagonized
      formation of stress fibers induced by lysophosphatidic acid. Our findings
      demonstrate that the interactions between actin and fragmin are tightly regulated
      by the cytosolic Ca2+ concentration and this provides a basis for a more general
      mechanism in higher organisms to regulate microfilament organization.

PMID- 9601100
TI  - Partial denaturation of small chromatin fragments: direct evidence for the radial
      distribution of nucleosomes in folded chromatin fibers.
AB  - To examine the internal structure of chromatin fibers, we have developed
      procedures for partial denaturation of small chromatin fragments (8-30
      nucleosomes) from chicken erythrocytes. Electron micrographs of samples prepared
      under conditions that cause nucleosome dissociation show rods and loops
      projecting from short compact fibers fixed by glutaraldehyde in 1.7 mM Mg2+.
      According to previous studies in our laboratory, these images correspond to the
      top view of partially denatured fibers. Our results indicate that rods and loops
      consist of extended duplex DNA of different lengths. DNA in loops is nicked, as
      demonstrated by experiments performed in the presence of high concentrations of
      ethidium bromide. Length measurements indicate that the radial projections of DNA
      are produced by unfolding of nucleosomal units. Loops are formed by DNA from
      denatured nucleosomes in internal positions of the fiber; DNA from denatured
      nucleosomes in terminal positions form rods. Our micrographs show clearly a
      radial distribution of DNA loops and rods projecting from fibers. Rods are
      orthogonal to the surface of the chromatin fragments. Considering that the high
      ionic strength used in this study (0.8-2.0 M NaCl) neutralizes the electrostatic
      repulsions between rods and fiber, this observation suggests that rods are
      extensions of nucleosomes radially organized inside the fiber. The position of
      the entry points of DNA loops into the fiber could be influenced by constraint on
      loops, but our results showing that the arc that separates these points in
      dinucleosome loops is relatively short suggest that consecutive nucleosomes are
      relatively close to each other in the folded fiber.

PMID- 9601101
TI  - The S. cerevisiae CLU1 and D. discoideum cluA genes are functional homologues
      that influence mitochondrial morphology and distribution.
AB  - The cluA gene, encoding a novel 150 kDa protein, was recently characterized in
      Dictyostelium discoideum; disruption of cluA impaired cytokinesis and caused
      mitochondria to cluster at the cell center. The genome of Saccharomyces
      cerevisiae contains an open reading frame (CLU1) that encodes a protein that is
      27% identical, 50% similar, to this Dictyostelium protein. Deletion of CLU1 from
      S. cerevisiae did not affect cell viability, growth properties, sporulation
      efficiency, or frequency of occurrence of cells lacking functional mitochondria.
      However, in clu1Delta cells the mitochondrial reticulum, which is normally highly
      branched, was condensed to one side of the cell. Transformation of cluA-
      Dictyostelium mutants with the yeast CLU1 gene yielded amoebae that divided
      normally and had dispersed mitochondria. The mitochondria in cluA- Dictyostelium
      cells complemented with CLU1 were not as widely scattered as in cluA+
      Dictyostelium cells, but formed loose clusters throughout the cytoplasm. These
      results indicate that the products of the CLU1 and cluA genes, in spite of their
      limited homology, are functional homologues.

PMID- 9601102
TI  - The small GTP-binding protein RacG regulates uroid formation in the protozoan
      parasite Entamoeba histolytica.
AB  - Entamoeba histolytica is a protozoan parasite that invades human intestine
      leading to ulceration and destruction of tissue. Amoebic movement and
      phagocytosis of human cells is accompanied by characteristic changes in cell
      morphology. Amoebae become polarized, developing a frontal pseudopod and a well
      defined rear zone of membrane accumulation designated the uroid. In motile
      eukaryotic cells, a phenomenon that contributes to movement is the capping of
      receptors at the cell surface. During the capping process, E. histolytica
      concentrates ligand-receptor complexes in the uroid. Interestingly, some of these
      surface receptors are involved in the survival of the parasite. While looking for
      regulators of capping and uroid formation, we identified RacG, an E. histolytica
      protein that is homologous to human Rac1. This protein belongs to the Rac
      subfamily of small GTPases implicated in interactions between the actin
      cytoskeleton and the membrane of mammalian cells. Cloning of the EhracG gene and
      analysis of the protein activity either in murine fibroblasts or in E.
      histolytica revealed that EhRacG induces a characteristic Rac phenotype. When
      expressed in amoebae, an EhRacG-V12 mutant protein not only deregulated cell
      polarity, but also caused a defect in cytokinesis. Analysis of the cytoskeleton
      in amoebae bearing this mutant revealed that F-actin concentrated at the
      periphery of the cell. In addition, the number and localization of uroids were
      modified. These results suggest a role for EhRacG in amoebic morphogenesis and
      cytokinesis.

PMID- 9601103
TI  - Identification of connexin43 as a functional target for Wnt signalling.
AB  - Wnt mediated signal transduction is considered to regulate activity of target
      genes. In Xenopus embryos, ectopic Wnt1 and Wnt8 expression induces gap
      junctional communication. During murine brain formation, Wnt1 and the gap
      junctional protein connexin43 (Cx43) are co-expressed at the mid/hindbrain
      border, while interference with Wnt1 or Cx43 expression during embryogenesis
      leads to severe brain defects in the mid/hindbrain region. In PC12 cells, Wnt1
      expression leads to an apparent increase in cell-cell adhesion. We investigated
      the effects of Wnt1 overexpression on gap-junctional communication in PC12 cells.
      Wnt1 expressing clones displayed an increased electrical and chemical coupling.
      This coincides with an increased expression of Cx43 mRNA and protein, while other
      connexins, Cx26, Cx32, Cx37, Cx40 and Cx45, were not up-regulated. Also,
      induction of Wnt1 expression in a mammary epithelial cell line leads to an
      increase in gap-junctional communication and Cx43 protein expression. In
      transient transactivation assays in P19 EC cells we found that Wnt1 and Li+, an
      ion that mimics Wnt signalling, increased transcription from the rat Cx43
      promoter, potentially via TCF/LEF binding elements, in a pathway separate from
      cAMP-induced Cx43 transactivation. The results demonstrate that Cx43 acts as a
      functional target of Wnt1 signalling, and Cx43 expression can be regulated by
      Wnt1 at the transcriptional level. Our data suggest that Wnt1-induced cell fate
      determination is likely to involve regulation of gap-junctional communication.

PMID- 9601104
TI  - The Polo-like kinase Plx1 is a component of the MPF amplification loop at the
      G2/M-phase transition of the cell cycle in Xenopus eggs.
AB  - We have investigated whether Plx1, a kinase recently shown to phosphorylate
      cdc25c in vitro, is required for activation of cdc25c at the G2/M-phase
      transition of the cell cycle in Xenopus. Using immunodepletion or the mere
      addition of an antibody against the C terminus of Plx1, which suppressed its
      activation (not its activity) at G2/M, we show that Plx1 activity is required for
      activation of cyclin B-cdc2 kinase in both interphase egg extracts receiving
      recombinant cyclin B, and cycling extracts that spontaneously oscillate between
      interphase and mitosis. Furthermore, a positive feedback loop allows cyclin B
      cdc2 kinase to activate Plx1 at the G2/M-phase transition. In contrast,
      activation of cyclin A-cdc2 kinase does not require Plx1 activity, and cyclin A
      cdc2 kinase fails to activate Plx1 and its consequence, cdc25c activation in
      cycling extracts.

PMID- 9601105
TI  - The 'ligand-induced conformational change' of alpha 5 beta 1 integrin. Relocation
      of alpha 5 subunit to uncover the beta 1 stalk region.
AB  - Integrin heterodimers undergo a conformational change upon the binding of ligand
      to their extracellular domains. An anti-beta1 integrin monoclonal antibody AG89
      can detect such a conformational change since it recognizes a ligand-inducible
      epitope in the stalk-like region of beta1 subunits. The binding of a 125I-labeled
      AG89 Fab fragment to alpha5 beta1 integrins on K562 cells was assessed and
      analyzed by the Scatchard method. High affinity binding sites for AG89 are
      present on cells treated with ligand peptide. In addition, results revealed that
      cells treated with EDTA also express AG89 binding sites with the same affinity
      although the number of binding sites is 4-fold lower. AG89 immunoprecipitated
      alpha5 beta1 complexes from surface-labeled K562 cells treated with ligand
      peptide. By contrast, it immunoprecipitated only beta1 chains when the ligand
      peptide was absent, suggesting that high affinity binding sites on EDTA-treated
      cells are associated with non-functional beta1 monomer. Additional studies show
      that the epitope for AG89 is constitutively exposed on mutant beta1 that cannot
      complex with alpha5. These data suggest that the AG89 epitope is masked by the
      alpha5 subunit. Ligand binding and integrin activation may uncover the beta1
      stalk region by triggering a conformational shift of alpha5 relative to beta1.

PMID- 9601106
TI  - Natural selection and the evolutionary history of major histocompatibility
      complex loci.
AB  - The major histocompatibility complex (MHC) is a multi-gene family unique to the
      vertebrates, whose products function to present peptides to T cells. Certain MHC
      loci are highly polymorphic, and this polymorphism is maintained by a form of
      balancing selection, probably overdominant selection. This selection has several
      consequences for MHC biology that make these genes different from neutrally
      evolving genes: an enhanced rate of nonsynonymous nucleotide substitution in
      codons encoding the peptide-binding region; long-lasting ("trans-species")
      polymorphism; and homogenization of introns relative to exons as a result of
      recombination and subsequent genetic drift. The MHC also reveals evidence of
      processes shared with other multi-gene families, including gene duplication and
      deletion and a low level of inter-locus recombination.

PMID- 9601107
TI  - Prostate cancer: a hazard also to be considered in the ageing male patient with
      spinal cord injury.

PMID- 9601108
TI  - Selecting candidates for a lower limb stimulator implant programme: a patient
      centred method.
AB  - OBJECTIVE: To develop an effective selection procedure for lower limb functional
      neurostimulation (LLFNS) for standing in paraplegia. DESIGN: The selection
      procedure and exclusion criteria were based on the previous experience for two
      clinical centres with experience of LLFNS. SETTING: Two Regional Spinal Injuries
      units in southern England. SUBJECTS: 254 fully rehabilitated paraplegics living
      in the community. INTERVENTION: Patients were invited to participate in the
      programme, and if suitable to subject themselves to a rigorous staged selection
      procedure from which they could withdraw at any time. OUTCOME MEASURE:
      Functionally successful home standing using closed-loop surface electrical
      stimulation. RESULTS: 57/254 patients were suitable on paper and were accessible.
      19 of these (CI = 10-28) were interested in the project and attended one of the
      spinal centres for details. Twelve (CI = 5-19) of these fulfilled the selection
      criteria and started on the training programme; and 10 of them completed the
      muscle training programme successfully. Seven patients (CI = 2-12) achieved
      closed-loop standing in the laboratory and four patients (CI = 1-8) did so at
      home.

PMID- 9601109
TI  - Treatment of chronic ventilatory failure using a diaphragmatic pacemaker.
AB  - We present our series of patients with chronic ventilatory failure treated with
      electrophrenic respiration: 13 males and nine females with a mean age of 12 +/-
      11.5 years. The etiology was, 13 tetraplegia, five sequelae of surgical treatment
      of intracranial lesions, and four central alveolar hypoventilation. The mean
      duration of the conditioning period were 3-4 months. Eighteen patients (81.8%)
      achieved permanent, diaphragmatically-paced breathing with bilateral stimulation
      and in four (18.2%) patients, pacing was only during sleep. Five patients died
      (22.7%): two during the hospital stay and three at home; two deaths had unknown
      cause and three were due respectively to, lack of at-home care, recurrence of an
      epidermoid tumor, and sequelae of accidental disconnection of the mechanical
      ventilation before beginning the conditioning period. Two cases were considered
      failures: One patient had transitory neurapraxia lasting 80 days, and the other
      had an ischemic spinal cord syndrome with progressive deterioration of the left
      side response to stimulation. One patient had right phrenic nerve entrapment by
      scar tissue and four suffered infections. The follow-up periods since pacemaker
      implantation are currently: 1, 11 years; 4, 10 years, and 17, less than 5 years.
      The results of our experience demonstrate that complete stable ventilation can be
      achieved using diaphragmatic pacing and that it improves the prognosis and life
      quality of patients with severe chronic respiratory failure.

PMID- 9601110
TI  - Tendon transfers in tetraplegic patients: the Cleveland experience.
AB  - The author has taken care of patients with spinal cord injury for over 30 years.
      A major part of these years was spent doing tendon transfers on the patients with
      tetraplegia. Thirteen were not better, but not worse out of the 285 patients who
      had an operation. All of the patients have had a period of rehabilitation, waited
      1 year following spinal injury, and had a stable neurological examination. The
      goals of the surgery were wrist extension, elbow extension, thumb pinch, and
      finger grasp. This was based on the author's classification of the characteristic
      muscle strengths that are present in the completely paralysed tetraplegic
      patient. One group of patients had weak or no wrist extension. These patients
      needed a transfer of the brachioradialis to the extensor carpi radialis brevis.
      Some of these patients required a posterior deltoid transfer to act as an
      obstacle to the brachioradialis. The next group of patients had no elbow
      extension, but had brachioradialis and two radial wrist extensors. They required
      a posterior deltoid transfer, and an opponens transfer and a transfer to give
      finger flexion. The next group had elbow extension, brachioradialis, two radial
      wrist extensors and a pronator teres, and needed an opponens transfer, and a
      transfer to give finger flexion. The last group of patients had poor or no
      opposition, and required an opponens transfer.

PMID- 9601111
TI  - Aging and life adjustment after spinal cord injury.
AB  - STUDY DESIGN: A field study of aging after spinal cord injury (SCI) was conducted
      by surveying the life adjustment of a large sample of participants with SCI.
      OBJECTIVES: The purpose of the current study was to compare life adjustment
      scores between cohorts of participants based on chronologic age, age at injury
      onset, time since injury and percentage of life with SCI. SUMMARY OF BACKGROUND
      DATA: Existing cross-sectional research suggests that age is negatively
      correlated and time since injury is positively correlated with life adjustment.
      However, few studies had investigated aging among people who have lived 30 or
      more years with SCI. METHODS: A total of 435 participants, 55 of whom were
      injured for 30 or more years, completed the Life Situation Questionnaire-Revised
      (LSQ-R), a measure of multiple SCI outcomes. RESULTS: Results indicated that
      being injured later in life is associated with a lower overall level of
      subjective well-being, poorer health, and a less active lifestyle. However,
      subjective well-being appears to improve throughout the life-cycle, even beyond
      30 years post-injury, thus neutralizing the adverse impact of age at onset on
      subjective well-being, but not on health or activities. CONCLUSIONS: The results
      suggest that rehabilitation professionals need to pay special attention to
      problems presented by being injured after the age of 40, particularly as it
      relates to activities. Living 30 or more years with SCI does not appear to
      present overwhelming barriers to adjustment.

PMID- 9601112
TI  - Mortality following spinal cord injury.
AB  - This study analyzed the mortality in 1453 spinal cord injured patients admitted
      early after injury to a specialised Spinal Injuries Unit within a University
      teaching hospital over a 40-year period. The cohort comprised 55.3% patients with
      cervical lesions and 44.7% patients with thoracic/lumbar lesions. Those patients
      who died within 18 months of the spinal injury (132) were excluded from the final
      analysis. Standardised Mortality Ratios, survival rates and life expectancy
      ratios were calculated for specific ranges of current attained age and duration
      since injury with reference to level and degree of spinal cord injury. The
      projected mean life expectancy of spinal cord injured people compared to that of
      the whole population was then estimated to approach 70% of normal for individuals
      with complete tetraplegia and 84% of normal for complete paraplegia (Frankel
      grade A). Patients with an incomplete lesion and motor functional capabilities
      (Frankel grade D) are projected to have a life expectancy of at least 92% of the
      normal population.

PMID- 9601113
TI  - A comparison of women and men with spinal cord injury.
AB  - While research on spinal cord injury (SCI) is abundant, few studies focus on
      women. This population-based study investigates differences in the prevalence of
      secondary conditions between 128 women and 522 men. Case managers retrospectively
      interviewed 650 persons regarding medical and psychological conditions secondary
      to SCI, as well as other life issues. Overall, males and females show more
      similarities than differences in the ways in which they manage life with SCI.
      Differences were found, though, regarding etiology of initial injury, insurance
      coverage, caregiver use, transportation use, medication use, and in other medical
      and behavioral areas. Females are significantly involved in more automobile
      crashes than males, while males are involved in more galls than females. Females
      are more reliant on Medicaid, while males report more Medicare and Worker's
      Compensation coverage. Females are more likely to have a paid attendant as a
      caregiver while males are more likely to have their spouse or parents assist.
      Males report more independence in their use of transportation than females. Males
      and females also report significant differences in the use of medication. Females
      are more likely to use medication any time it is a treatment option. Males are
      more active, use tobacco more and have more arm fractures postinjury than
      females.

PMID- 9601114
TI  - Cervical and breast cancer screening in wheelchair dependent females.
AB  - The aim of this study was to compare the attendance rates for cervical and breast
      cancer screening in wheelchair dependent spinal cord injured (SCI) women with
      those in the general female population in England. The study was conducted as a
      postal questionnaire survey with an effective response rate of 79%. The
      attendance rates of the eligible SCI groups were 84% for cervical screening and
      72% for mammography, both figures being well within the national average
      attendance rates in the general female population. Difficulties with cervical
      screening were reported in 58% and with mammography in 43% of the cases,
      including restricted access to clinics, examining rooms and examining couches and
      positioning during the procedure. These were also the main reasons given for non
      attendance. The article points out ways to enable even more wheelchair dependent
      women to benefit from the preventative screening programmes.

PMID- 9601115
TI  - Audit of bladder neck resection in spinal cord injured patients.
AB  - An audit was carried out at Ibn Al-Kuff Spinal Injuries Hospital, Baghdad, Iraq,
      to try to establish the value of bladder neck resection in the neuropathic
      bladder of spinal injured patients. Spinal cord injured men who underwent bladder
      neck resection and/or external sphincterotomy were identified and their bladder
      management and post-operative outcome was reviewed. Some patients were available
      for objective assessment with urodynamics. Results of this procedure are
      discussed. Blind bladder neck resection, ie without prior urodynamic appraisal,
      was found to be useless in achieving bladder management goals.

PMID- 9601116
TI  - Traumatic spinal cord injury complicating ankylosing spondylitis.
AB  - The aim of this paper is to review the incidence and characteristics found in
      traumatic spinal cord injury (SCI) occurring in patients with long-standing
      ankylosing spondylitis (AS). The incidence of patients with traumatic SCI
      admitted to our unit from January 1984 to February 1996 was 2% (15 out of 893).
      They were all men with a mean age of 56 years. Most frequently the etiology of
      the lesion was a motor vehicle accident and the injury was mainly due to a
      hyperextension mechanism. Acute spinal fracture occurred in 13 patients, all
      involving the cervical region. No fracture was observed in two patients with
      thoracic neurological level. Three patients presented with an interval free
      period of neurological symptoms in whom a spinal epidural hematoma was visualized
      with magnetic resonance imaging. On admission eight patients were diagnosed as
      having complete SCI and the other seven an incomplete SCI. In the acute phase,
      respiratory complications were most frequent, causing six patients to die.
      Treatment was conservative in 14 patients. Multidisciplinary management of these
      patients should be implemented in an institution equipped with both a Spinal
      Injury Unit and an Intensive Care Unit.

PMID- 9601117
TI  - The neurological outcome of acute spinal cord injury in a neurosurgical hospital
      of a developing country.
AB  - The neurological outcome of 146 patients who survived spinal cord injury in a
      neurosurgical hospital of a developing country, were compared to those reported
      from Stoke Mandeville, UK. The average recuperation in the two groups was
      similar.

PMID- 9601118
TI  - Shepherd Center.

PMID- 9601119
TI  - Primary intraparenchymatous spinal cord melanoma.
AB  - A case of primary melanoma arising from the spinal cord parenchyma at the Th 10
      11 level, in a 50-year old female, is presented. In this patient, Magnetic
      Resonance Imaging (MRI) showed an intraparenchymatous lesion, with rounded
      borders, and an associated intramedullary cyst. On the basis of these findings
      and the long duration of symptoms, an erroneous preoperative diagnosis of
      intramedullary ependymoma was made.

PMID- 9601120
TI  - Metastatic choriocarcinoma in the thoracic extradural space: case report.
AB  - A case is reported of a 44-year old woman with metastatic choriocarcinoma of the
      thoracic extradural space causing paraplegia. Spinal cord compression due to an
      extradural deposit is an emergency in neurosurgical practice. The majority of
      these lesions are metastatic. To our knowledge choriocarcinoma metastases and
      extradural cord compression in the spinal canal is the first case reported in the
      neurosurgical literature.

PMID- 9601121
TI  - Re: The importance of osmolality in hydrophilic urethral catheters: a crossover
      study, Waller et al. Spinal Cord (1997) 35: 229-233.

PMID- 9601122
TI  - Memorial. Roger Olaf Egeberg 1904-1997.

PMID- 9601123
TI  - Academic medicine's changes and challenges.

PMID- 9601124
TI  - Chiaroscuro hematopoietic stem cell.
AB  - These observations suggest several immediate clinical strategies. In gene
      therapy, approaches could be targeted to obtain cycling of hematopoietic stem
      cells and gene-carrying retrovirus vector integration followed by engraftment at
      an appropriate time interval which favors engraftment. The same type of approach
      can be utilized for stem cell expansion approaches. Alternatively marrow or
      peripheral stem cell engraftment can be obtained with minimal to no toxicity in
      allochimeric strategies in such diseases as sickle cell anemia or thalassemia. A
      similar approach could be useful in obtaining cell engraftment with minimal
      toxicity in therapies employing cellular immune (T-cell and NK-cell) attack
      against cancer. These areas of clinical application are outline in Table 3.

PMID- 9601125
TI  - The discovery, development and clinical applications of granulocyte colony
      stimulating factor.
AB  - The story of the discovery, development and applications of G-CSF illustrates
      many of the best features of modern laboratory and clinical investigation. The
      initial discovery of the CSFs was somewhat serendipitous. The pathway to
      understanding the cellular and molecular base for the action of these substances
      was long, but fruitful and exciting for those who pursued it tirelessly. The
      power of modern molecular biology is illustrated by the rapid advances which
      followed the cloning of the G-CSF gene. Major advances in our understanding of
      the regulation of neutrophil production and deployment have followed, together
      with many important clinical observations. To date hundreds of thousands of
      patients have been treated with G-CSF and some individuals with severe chronic
      neutropenia have received daily therapy for more than ten years. Results of
      recent studies suggest that there will be many more interesting and important
      clinical applications for G-CSF.

PMID- 9601126
TI  - Immune modulation of cardiac cell function.

PMID- 9601127
TI  - To dig or not to dig.

PMID- 9601128
TI  - Peripheral bone densitometry: an old friend revisited.
AB  - The earliest assessments of bone "mass" involved metacarpal morphometry that
      provided insight into age-related changes, the effects of low habitual dietary
      calcium intake, and the effects of estrogen deficiency and replacement. Single
      photon absorptiometry (SPA) made quantitative mass measurement possible but this
      was intellectually unsatisfactory since osteoporotic fractures are more of a
      concern at the spine and hip than at the wrist. Necessity forced the development
      of axial bone mass measurement (dual photon absorptiometry--DPA, dual energy xray
      absorptiometry--DXA, quantitative computed tomography--QCT). Hip measurements
      provide a better prediction of hip fracture risk than measurements at any other
      skeletal site. For every standard deviation decrement of bone mass at the hip,
      relative risk of fracture is 3.0. At non-hip sites the relative risk is only 2.0
      for each standard deviation decrement in bone mass. However measurement at non
      hip sites provide a fracture risk prediction that is at least the equal of blood
      pressure measurement for predicting risk of CVA, and substantially better than
      the risk assessment of acute MI afforded by cholesterol measurement. An important
      caveat of the superiority of hip measurement is that the data are derived from
      short-term studies in older women (> 70 years). The relative risk data from
      phalangeal, forearm, and heel measurements have all been obtained from longer
      term studies in younger women. From a community health perspective, bone density
      measurements, no matter how accurate, precise, and meaningful, have limited value
      if access to the technology is limited. Peripheral measurements can be obtained
      on existing radiographic equipment (phalanges), or small, portable, inexpensive
      dedicated equipment (forearm, heel). This technology is more likely to make it to
      the office of the primary care physician than the larger, more expensive,
      dedicated equipment needed for hip measurements. The peripheral measurement
      technology is also suitable for high traffic areas, just as blood pressure and
      cholesterol measurements are widely available. This presentation reviewed the
      scientific validity of peripheral bone mass measurement and explored the
      potential for making this technology available at non-traditional facilities such
      as pharmacies, shopping malls, health clubs, etc.

PMID- 9601129
TI  - Fish stories: 100 years at Mount Desert Island Biological Laboratory.

PMID- 9601130
TI  - The Gordon Wilson Lecture. Growth hormone replacement in adults and other uses.
AB  - The modern era of growth hormone research began in 1981 with the characterization
      and synthesis of the primary stimulator of GH synthesis and secretion, growth
      hormone releasing hormone. Discovery of this peptide and studies in human adults
      and children resulted in unraveling the complex nature of the regulation of GH
      secretion. Discovery of regulatory mechanisms has permitted a greater
      understanding of normal and abnormal growth hormone physiology. The use of growth
      hormone therapeutically as replacement in GH deficient adults is in its medical
      infancy, but preliminary studies indicate a beneficial effect on body
      composition, serum lipid concentrations, bone mineral density, muscle strength,
      and exercise endurance. These studies over the past decade resulted in Food and
      Drug Administration approval of GH for replacement in adults with hypothalamic or
      pituitary disease. It remains to be determined whether or not chronic GH
      replacement will have beneficial effects on morbidity and mortality. The use of
      growth hormone in other areas such as aging, catabolic illness, obesity,
      diabetes, and muscular disorders is under active investigation and risks and
      benefits remain to be determined.

PMID- 9601131
TI  - Involvement of heme in the antimalarial action of chloroquine.
AB  - When malaria parasites digest hemoglobin, they release FP intracellularly. FP is
      an oxidized form of heme which is toxic for biological membranes. The parasites
      are not poisoned when they digest hemoglobin, however, because they sequester FP
      in hemozoin. In fact, the refractile, dark brown substance in hemozoin is
      sequestered FP. Chloroquine binds tightly to nonhemozoin FP and, under certain
      circumstances, enhances its toxicity. In addition, chloroquine interferes with FP
      sequestration and causes toxic nonhemozoin FP to accumulate to lethal levels in
      erythrocytes parasitized with malaria parasites. Evidently, this is how
      chloroquine kills malaria parasites. It is desirable, therefore, to know more
      about FP sequestration and how it is affected by chloroquine. Malaria parasites
      possess a catalyst for FP sequestration which is modulated by treatment with
      quinoline antimalarial drugs such as chloroquine and quinine. Chloroquine
      treatment causes the activity of the catalyst to decrease by 80 to 90 percent.
      Quinine treatment has no obvious direct effect on the catalyst for FP
      sequestration. Nevertheless, quinine treatment antagonizes and reverses the
      chloroquine-induced loss of ability to sequester FP. The effect of chloroquine
      treatment also is antagonized by various metabolic inhibitors, including
      inhibitors of protein biosynthesis such as cycloheximide. These findings indicate
      that chloroquine, like quinine, does not interact directly with the catalyst for
      FP sequestration. Instead, they are evidence that chloroquine acts by increasing
      the amount, accessibility, or reactivity of a regulator of the catalyst for FP
      sequestration. I propose that chloroquine increases the amount of the regulator,
      which inactivates the catalyst for FP sequestration, which leads to accumulation
      of nonhemozoin FP, which binds with high-affinity to chloroquine and which
      ultimately kills the malaria parasite.

PMID- 9601133
TI  - Atherosclerosis as disease of redox-sensitive genes.
AB  - Accumulating evidence provides a compelling case that one of the major
      pathophysiologic mechanisms involved in the pathogenesis of atherosclerosis is
      enhanced oxidative stress and that the most important manifestation of this
      altered redox state is the modulation of a set(s) of proinflammatory genes that
      are regulated directly or indirectly by reactive oxygen species. Viewed in this
      perspective the oxidation of LDL is but one important consequence of a
      generalized metabolic abnormality of the arterial wall in atherosclerosis rather
      than being the core pathophysiological feature. The fact that
      hypercholesterolemia, hypertension, and AGEs related to diabetes mellitus all
      activate similar redox-sensitive proinflammatory genes associated with the
      pathogenesis of atherosclerosis provides the potential for the development of
      unifying concepts concerning the etiology of the disease. These concepts also
      provide additional evidence that antioxidants may be potentially attractive
      therapeutic agents.

PMID- 9601132
TI  - Colon cancer: polyps, prevention, and politics.

PMID- 9601134
TI  - Analgesic nephropathy.
AB  - At least two distinct forms of analgesic nephropathy are presently recognized.
      One form is classical analgesic nephropathy that is associated with habitual
      consumption of predominantly combination analgesic products. This disease takes
      many years to develop and is characterized by a dense interstitial fibrosis and
      the insidious development of renal failure. Renal papillary necrosis had been
      classically associated with this illness. New diagnostic tests to make an early
      diagnosis of the lesion may be on the horizon with the recognition that the non
      contrasted CT scan may be useful. Further studies will be necessary to confirm
      this in the U.S. population of analgesic users. The second form of analgesic
      nephropathy is typically an acute renal failure associated with the use of
      nonsteroidal anti-inflammatory drugs. In part this disease has been predictable
      based on the fact that there is an at-risk population of patients who are more
      vulnerable to developing it. Other features of nonsteroidal induced toxicity are
      also recognized (see Table 3). It is hoped that the increased recognition that
      chronic and acute analgesic use may lead to renal failure will result in
      strategies that will apprise consumers and physicians of this risk, and thereby
      lead to reduction in the prevalence of these two forms of analgesic-related
      kidney disease.

PMID- 9601135
TI  - Listeria and Shigella actin-based motility in host cells.

PMID- 9601136
TI  - The old eugenics and the new science.

PMID- 9601137
TI  - The Jeremiah Metzger Lecture. Vaccine prophylaxis today: its science, application
      and politics.
AB  - In summary, I have addressed 5 key issues concerning vaccines today. First is the
      essentially empiric nature of vaccinology. Vaccinology is not a rational science.
      Each idea must be tested by experiment. This need for trial and error
      experimentation is a substantial barrier to new vaccines. The proven track record
      of existing vaccines to eradicate disease, to reduce occurrence of disease,
      reduce human suffering and contain health care spending--when coupled with the
      potential for new discoveries against significant disease targets--is
      unparalleled by other therapeutic areas. The complexity of vaccine delivery today
      in clinical practice with 15-17 injections in the first two years of life
      emphasizes the need for development of combination pediatric vaccines, for
      example, putting DTaP, HBV, HIB, and IPV together. This has proved to be far more
      difficult than previously believed due to unpredicted immune interference and
      incompatibilities on mixing of different components, demonstrating again the
      inadequacy of our understanding of how vaccines work and the empiric nature of
      the science. Similar complexity will face adult vaccines in the future, as new
      adult vaccines are developed. Next, vaccines remain undervalued by people, by
      government, and by society. Government-controlled prices in many areas of the
      world prohibit a return on investment that supports innovative R&D. New vaccines
      may be unavailable in certain markets because of pricing restraints. Prices of
      new vaccines in the developed world will rise as will prices in the developing
      world for products currently available only in the developed world. Reluctance to
      use vaccines is an especially disturbing symptom of the undervaluation issue. In
      the U.S., school entry requirements have kept childhood immunization rates high
      by five years of age. But this is a new phenomenon, driven in part by the measles
      outbreaks. The risk is that history will repeat itself. In the absence of disease
      and lack of public knowledge of these diseases, complacency sets in, immunization
      rates fall, with the expected result on occurrence of disease. For adults, we may
      hope that managed care with its interest in cost saving and disease prevention
      may actually help in achieving the goals of the Year 2000. Finally, I have talked
      about the anti-vaccine attitudes and forces that impede control of disease by
      vaccines. It is important that new initiatives be undertaken that will be
      successful in providing a balanced view of vaccine safety, efficacy and benefits
      to the public, to the provider and to the payers.

PMID- 9601138
TI  - The Theodore E. Woodward Award. Mycobacterium avium and slender women: an
      unrequited affair.

PMID- 9601139
TI  - New and emerging infectious diseases.

PMID- 9601140
TI  - Professional and moral development in medical students: the ethics of caring for
      patients.

PMID- 9601141
TI  - Teaching medical students in an office setting. The apprentice system revisited;
      a cardiologist's perspective.

PMID- 9601142
TI  - Peter's Medicine--lessons from the 13th century.

PMID- 9601143
TI  - The pharmacokinetics of moxidectin after oral and subcutaneous administration to
      sheep.
AB  - The pharmacokinetic parameters of moxidectin were determined in ten sheep
      following a single subcutaneous or oral drench at a dose of 0.2 mg.kg-1. The
      plasma kinetics were best fitted by a two-compartment model. Moxidectin was
      detected in the plasma at the first sampling time (1 h) and thereafter for at
      least 60 d. The AUC were similar after both treatments indicating the same
      bioavailability for the two routes of administration. The oral route was
      characterized by a higher Cmax value (28.07 ng.mL-1 than after subcutaneous
      injection (8.29 ng.mL-1 and by significantly faster absorption as indicated by
      Tmax of 0.22 d and 0.88 d for oral and subcutaneous administrations,
      respectively. The most striking result of this experiment was the longer mean
      residence time reported for the subcutaneous route, i.e. 16.80 d as compared to
      12.55 d for the oral drench. This differences is in agreement with previous
      studies demonstrating the longer anthelmintic efficacy of the subcutaneous route
      in comparison with oral administration.

PMID- 9601144
TI  - Urinary excretion of catecholamines, cortisol and their metabolites in Meishan
      and large white sows: validation as a non-invasive and integrative assessment of
      adrenocortical and sympathoadrenal axis activity.
AB  - Urinary free corticoids (cortisol and cortisone), catecholamines (norepinephrine
      or NE, epinephrine or E, dopamine or DA, and their O-methoxylated metabolites) as
      well as creatinine (Cr) were analysed in 42 spontaneously voided urine samples
      from Large White (LW, n = 20), Meishan (MS, n = 6), and LW x MS (F1, n = 16)
      lactating sows. The cortisol concentration in the urine of MS (28.1 pg/micrograms
      Cr) was five-fold greater than that of LW sows (6.2 pg/micrograms Cr, P < 10(
      4)). F1 were intermediate (12.0 pg/micrograms Cr). Mean cortisone concentration
      was also larger in MS (13.5 pg/micrograms Cr) compared to LW (7.1 pg/micrograms
      Cr, P < 0.01). Although the differences were less pronounced, the concentrations
      of the catecholamines were also greater in MS than in LW sows (norepinephrine:
      25.4 versus 5.9 pg/micrograms Cr, epinephrine: 8.7 versus 2.8 pg/micrograms Cr
      and dopamine: 59.2 versus 17.8 pg/micrograms Cr, P < 10(-4)). These results
      confirmed the hypercortisolism state of MS pigs previously shown by plasma
      cortisol assay and supported the hypothesis that the sympathetic nervous system
      is hyperactive in this breed. These urinary investigations may offer possible
      applications for the assessment of chronic stress.

PMID- 9601145
TI  - [Assessing the accuracy of the practice of a method of scoring the body condition
      of ewes within a professional framework].
AB  - The accuracy of the body condition scoring for ewes using lumbar palpation was
      assessed by mean of an experiment conducted under conditions close to those
      occurring everyday on the farms. Thirteen operators evaluated the body condition
      score twice in a sample of 48 Lacaune breed dairy ewes, using a semi-quantitative
      grid (from 0 to 5 points, with a 0.25 point precision). Under the experimental
      conditions, the repeatability of the method, i.e. the comparison between the
      scores given by the same operator to the same animals for the two successive
      scoring notations, was good and even very good (Kappa test), if a 0.25 point
      precision is tolerated. On the other hand, the reproducibility, i.e. the
      comparison between the scores given to the same animals by differents operators
      was poor. Therefore, this method is easy to master for the management of a given
      flock by a single person. However in order to make comparisons between flocks, in
      reference to body condition standards set up for different farming systems, this
      method needs greater precision. Some of the application conditions required for
      this are discussed.

PMID- 9601146
TI  - Nematode genera diversity in cattle: similarity of between-sire progenies.
AB  - Breeding cattle for resistance to nematode infection is mostly based on egg
      excretion. This, however, does not allow for generic identification of the
      nematodes involved. Unless we know whether the selected resistance is directed
      against one or several particular genera, a strong bias could be introduced in
      the selection programs. In order to estimate the likelihood of this potential
      bias we investigated nematode genera diversity in the progeny of four sires in
      1992 and seven sires in 1994. Three of the four Aberdeen Angus sires used in 1992
      were related while the seven sires in 1994 were unrelated. Diversity was assessed
      using at least ten individual faecal cultures for each progeny group during each
      of the two sampling periods (beginning and end of grazing period, April and
      September). It was estimated by the relative proportion of each genera
      (Ostertagia, Cooperia, Haemonchus, Trichostrongylus and Oesophagostomum) or by
      either the Shannon (genera diversity) or Pielou (genera evenness) index. The
      Shannon index was repeatable when measured at 2-week intervals within the same
      progeny group on ten random faecal samples. No significant difference was
      recorded between sire genera diversity over the two sampling periods. This
      indicated that hosts have a limited effect on the nematode genera diversity as
      assessed by faecal cultures, and that the selection of resistant hosts could
      probably be achieved using faecal egg counts.

PMID- 9601147
TI  - Ribotyping of Staphylococcus caprae isolated from goat milk.
AB  - The usefulness of the API-STAPH system and a method based on ribosomal
      fingerprinting was evaluated by studying 89 coagulase-negative staphylococci
      isolated from goat milk. The bacteria were supposed to belong to the species
      Staphylococcus caprae. The results obtained from the API-STAPH system showed
      variations in their phenotypic features. DNA cleavage with EcoRI yielded six
      ribotypes and three distinct patterns were generated when the DNA of the strains
      was digested with HindIII. Forty-six strains were correctly characterized as S.
      caprae by the two methods. In addition, 37 isolates having atypical biochemical
      profiles with the API-STAPH system were confirmed as being S. caprae by the
      ribotyping. Three strains remained unclassified by both methods. Ribotypes
      generated by HindIII were found to be the most informative for species
      determination, whereas the number of bands generated by EcoRI indicated the
      usefulness of this enzyme in S. caprae typing.

PMID- 9601148
TI  - Factors associated with clinical mastitis incidence in French dairy herds during
      late gestation and early lactation.
AB  - A prospective epidemiological survey was conducted in dairy herds in Brittany
      (France), concerning 139 herd-years. The data were divided into ten 14 herd-year
      groups (deciles) and three of these were compared using discrimination by
      barycentric analysis to study herd late gestation and early lactation variables
      associated with the annual incidence of herd clinical mastitis in the first 60
      days of gestation (CMAI). The first decile included herd-years with low CMAI (o
      to 4.6%), the second decile, herd-years with medium CMAI (11.6 to 14.3%) and the
      last decile, herd-years with high CMAI (26.3 to 45.5%). Herd data included diet
      components, milk yield and reproduction parameters, clinical diseases, body
      condition score, body dirtiness score and circulating biochemical and
      hematological markers. The high CMAI group had the following characteristics: 1)
      lower percentages of dried cows supplemented with vitamins 'ADE'; 2) higher
      levels of plasma ceruloplasmin and higher gamma glutamyl transferase activities
      (GGT) in the late gestation period; 3) higher percentages of winter calvings
      (December, January, February). Clinical mastitis risk could be controlled by
      supplementations with vitamins A, D and E in the late gestation period, because
      of the potential relationship between oxidative stress and mastitis. Higher GGT
      activities would be associated with Fasciolasis via common climatic risk factors
      (rainfall, humidity) for both mastitis and liver flukes. Winter calving and
      clinical mastitis would be associated with unfavourable hygiene conditions and
      stress at calving related to high animal density and bad weather conditions.
      Ceruloplasmin could be a specific predictor for mastitis risk through
      nutritional, immune and genetic interrelated factors.

PMID- 9601149
TI  - Peculiarities of vitamin D and of the calcium and phosphate homeostatic system in
      horses.
AB  - The aim of the present study was to investigate the importance of putative
      regulatory factors of the calcium (Ca) and inorganic phosphate (P(i)) homeostatic
      system in the horse. The concentrations of Ca, P(i), vitamin D metabolites,
      parathyroid hormone (PTH), the activity of the alkaline phosphatase (AP) and the
      concentration and binding properties of vitamin D binding protein (DBP) were
      measured in the plasma. In addition, the ability of the renal cortex to
      hydroxylate calcidiol into 24,25(OH)2D3 and 1,25(OH)2D3 was evaluated in vitro.
      The plasma concentration of Ca (3.2 +/- 0.15 mmol.L-1, N = 100) showed no
      significant differences between different horse breeds and was not influenced by
      Ca intake, exercise or by indoor maintenance. The concentration of plasma P(i)
      which ranged from 0.58 to 1.99 mmol.L-1 was negatively correlated with age and
      positively correlated with the P content of the feed. AP activities in plasma
      ranging from 131 to 852 U.L-1 were also negatively correlated with age tended to
      be higher in horses than in other domestic animals. Plasma concentrations of
      calcidiol and 24,25(OH)2D were much lower than in most other mammals and birds.
      The concentration and binding properties of DBP to calcidiol were not markedly
      different from those of other mammals. The mean plasma concentration of
      calcitriol (55 +/- 24 pmol.L-1, N = 19) was much lower than in other mammals. The
      plasma concentration of PTH was 218 +/- 181 ng.L-1. In renal cortex homogenates,
      only 25-hydroxycholecalciferol-24-hydroxylase activity could be detected (Vmax:
      0.42 +/- 0.11 pmol.min-1.mg-1 protein; Km: 373 +/- 263 nmol.L-1). In conclusion,
      this study provided evidence that in contrast to other species, vitamin D does
      not appear to play a key role in regulating Ca and P(i) homeostasis in horses.

PMID- 9601150
TI  - Experimental transmission of Cryptosporidium oocyst isolates from mammals, birds
      and reptiles to captive snakes.
AB  - Groups of four to five, 3-month-old rat snakes (Elaphe obsoleta) were separately
      gastrically inoculated with 2.0 x 10(6) viable oocysts of Cryptosporidium muris
      (mice and calves), C. muris-like (Bactrian camels), C. wrairi (guinea pigs), C.
      baileyi (chickens), C. meleagridis (turkeys), Cryptosporidium sp. (turtles,
      tortoises, chameleons and lizards) and C. serpentis from clinically (fatal case)
      and subclinically infected snakes. None of the snakes inoculated with oocysts
      originating from homothermous vertebrates developed infection as determined by
      histology and serology, whereas all snakes challenged with reptilian oocyst
      isolates were infected with Cryptosporidium on weeks 6 and 10 post-inoculation
      (PI). One week 10 PI, the snakes displayed mild to serve, multifocal to
      widespread, thinning and disorganization of gastric epithelium and nine out of
      twelve snakes infected by oocysts originating from reptiles other than snakes
      displayed severe gastric hyperplasia. Three out of ten snakes infected oocysts
      originating from snakes had ELISA-detectable Cryptosporidium-specific antibody
      (Ab) titers on week 6 PI; all snakes were Cryptosporidium-seroconverted on week
      10 PI and their serum Ab titer significantly increased. The study demonstrated
      that Cryptosporidium infections in snakes maintained on the diet of rodents or
      birds cannot be initiated via ingestion of an infected food item; however, snakes
      can void ingested oocysts. Lack of host specificity among reptiles to this
      pathogen, demonstrated for the first time in the present study, indicates that
      snake-attributed C. serpentis is not distinct from Cryptosporidium sp. infecting
      reptiles other than snakes, and that clinical manifestations and virulence of
      Cryptosporidium in snakes in modulated by the species of the host. Housing of
      snakes with other reptiles can enhance transmission of Cryptosporidium to snakes,
      and therefore should be avoided.

PMID- 9601151
TI  - Plasma lipid changes in the female mule duck (Cairina moschata x Anas
      platyrhynchos) experimentally infected with Eimeria mulardi.
AB  - Plasma levels of phospholipids, triglycerides, high density lipoproteins (HDL)
      cholesterol and HDL-phospholipids were studied in 48 11-d-old female mule ducks
      infected per os with 5 x 10(3) x 10(4) x 5 x 10(5) sporulated oocysts of Eimeria
      mulardi (D0), or kept as an uninfected control group. Data were recorded from D-1
      to D17. Mortality and weight loss were only observed with the 5 x 10(5) oocyst
      dose. Plasma phospholipids were significantly reduced with the two highest
      infecting doses on D3, and returned to normal values by D9 with the highest
      infecting dose. The minimum level attained was no lower than 74% of the control
      group. Triglyceride levels were reduced early but only slightly and irregularly
      in the three infected groups. HDL-cholesterol was significantly reduced from D5
      and HDL-phospholipids from D3. These reduced levels depended on the infecting
      dose and were lowest on D5, respectively 34 and 35% of the control group with the
      highest infecting dose. In this group, the levels remained lower than in the
      uninfected group on D17. These perturbations in blood lipid classes have been
      described in avian coccidiosis.

PMID- 9601152
TI  - Isolation of Mycobacterium bovis from baboons, leopards and a sea-lion.
AB  - This study reports on two series of cases of Mycobacterium bovis infection in zoo
      animals. The first was in a captive population of baboons (Papio hamadryas) and
      the second in a mixed group of wild mammals, including four leopards (Panthera
      uncia and Panthera pardus) and a sea-lion (Otaria byrona). The isolation and
      identification of strains of M. bovis confirmed the presence of M. bovis
      infections in both zoos. The epidemiological study using genetic markers such as
      the IS6110-based DNA fingerprinting system made it possible to differentiate
      between M. bovis strains. The M. bovis strains isolated from baboons were shown
      to contain a single IS6110 copy, as usually do cattle isolates, whereas the M.
      bovis strains isolated from the other exotic animals presented multiple copies.
      This finding suggests that the origin of the contamination for the baboons in zoo
      A could be related to cattle. The origin of the contamination for the leopards
      and sea-lion in zoo B is more difficult to determine. In conclusion, the authors
      suggest some recommendations for avoiding outbreaks of tuberculosis infections in
      zoos.

PMID- 9601153
TI  - A survey of transdermal fentanyl use in a major cancer center.

PMID- 9601154
TI  - Hyoscine in opioid-induced sweating.

PMID- 9601155
TI  - Proctoclysis for hydration of terminally ill cancer patients.
AB  - In a prospective, open study, 78 patients with terminal cancer received
      proctoclysis (rectal hydration) in four different centers. In all cases, a #22
      French nasogastric catheter was inserted approximately 40 cm into the rectum and
      an infusion of normal saline (2 cases) or tap water (76 cases) was administered
      at a rate of 250 +/- 63 cc/hr. Hydration was maintained for 15 +/- 8 days. The
      main reason for discontinuation of hydration was death (60 cases). The mean
      visual analogue score for discomfort after infusion (0 = no discomfort, 100 =
      worst possible discomfort) was 19 +/- 14. The costs of proctoclysis was estimated
      at Can$0.08 compared with Can$4.56 per day for hypodermoclysis, and Can$2.78 per
      day for intravenous hydration. Our results suggest that proctoclysis is a safe,
      effective, and low-cost technique for the delivery of hydration in terminally ill
      cancer patients.

PMID- 9601156
TI  - Pain medication during terminal care of children with cancer.
AB  - The purpose of this study was to evaluate the need for pain medication and the
      adequacy or inadequacy of the analgesia achieved, in children with cancer who
      died while in terminal care. Of the 100 pediatric patients with cancer treated at
      the Children's Hospital, University of Helsinki, Finland, who died during 1987
      1992, 70 died while in terminal care. The underlying diseases were leukemia (N =
      25), solid tumors (N =24), and brain tumors (N = 21). Of these children, 60% were
      treated at home, 29% at hospital, and 11% at both. The assessment of pain during
      terminal care was retrospective and included analysis of the patients' records
      and a structured interview of the two parents separately. In total 62 children
      (89%) received regular pain medication, with a mean duration of 17 days in
      children with leukemia, 58 days in those with solid tumors, and 66 days in those
      with brain tumors. Medication was usually started with anti-inflammatory drugs,
      then changed to oral opioids when deemed necessary, and finally to parenteral
      opioids. Parenteral morphine was administered to 40 children, to 30 as a
      continuous infusion through a central venous line. The dose of morphine was 0.8
      mg/kg/day at the start and was increased to 4.9 (range, 0.2-55) mg/kg/day. Of the
      62 children who received regular pain medication, the majority (81%) had adequate
      analgesia. In 19%, analgesia had been suboptimal. In conclusion, the vast
      majority of children with cancer need regular pain medication while in terminal
      care. This can be administered adequately at home, even if continuous intravenous
      infusions are required.

PMID- 9601157
TI  - Oral Morphine Consumption in Italy and Sicily.
AB  - The trend in morphine consumption in Italy and in Sicily was investigated, using
      sales of sustained-release formulations as an indicator. A slight increase in
      morphine consumption has been observed in the last few years. This trend was more
      evident in Sicily. Formulations with the lowest dose (10-30 mg) were more
      frequently used. Italian laws and restrictions concerning the medical use of
      opioids are the most sever in Europe. Although some countries have a high level
      of opioid consumption, the assertion that morphine consumption is an indicator of
      progress in cancer pain management is only valid in countries in which opioids
      are not generally used for other purposes, like in Italy. Continual medical
      education, postgraduate training courses, and the development of pilot programs
      of pain relief and palliative care may improve the knowledge of cancer pain.

PMID- 9601158
TI  - Experiences with the prescription of opioids: a patient questionnaire.
AB  - Forty-three German patients who had been treated with strong opioids were
      questioned about their experiences during therapy. The prescription of opioids
      was well accepted by most patients. Some, however, felt stigmatized by taking
      opioids. Fourteen patients (33%) were asked by their relatives, friends, or other
      patients about the special prescription form. Six patients (14%) had difficulties
      in redeeming the prescription at the pharmacy, seven patients (16%) were warned
      against taking the medication by the pharmacist, 21 patients observed that their
      general practitioner (GP) was mistrustful about the treatment, and 16 patients
      (37%) reported that the GP terminated the therapy. Despite the beneficial effect
      for the patient, opioid treatment started and supervised in a pain clinic is not
      always continued by the GP. In Germany, it may not be possible to administer
      opioid therapy outside of a specialized pain clinic. In those few cases in which
      an opioid therapy is successfully instituted, difficulties continue due to
      prejudices, insufficient education, and complicated prescription laws.

PMID- 9601159
TI  - Suggestion/placebo effects on pain: negative as well as positive.
AB  - This study explores the effect of positive and negative placebo suggestions on
      pain induced by hand exposures to ice water. Thirty-six participants were
      randomly assigned to one of the following interventions: (a) positive placebo
      suggestion, (b) negative placebo suggestion, and (c) control. The positive
      placebo-suggestion participants were given favorable messages about the
      beneficial effects of ice-water hand immersion. The negative placebo-suggestion
      group was given messages depicting the negative effects of exposure to ice water.
      The control groups were given neutral messages about exposure to ice water.
      Participants rehearsed the messages and focused on them during their second hand
      exposures. Results indicate that both the positive and negative placebo
      suggestion interventions significantly altered participants' pain threshold, pain
      tolerance, and pain endurance. Participants exposed to a positive placebo
      condition tolerated pain better than a neutral condition. Participants exposed to
      a negative placebo did not tolerate pain as well as participants with a neutral
      condition.

PMID- 9601160
TI  - Efficacy of analgesics in chronic pain: a series of N-of-1 studies.
AB  - Rational drug treatment of chronic musculoskeletal pain remains a challenge.
      Although commonly prescribed, the true efficacy of opioid analgesics or of
      nonsteroidal antiinflammatory drugs remains to be established. Using an N-of 1
      design, eight patients with regional cervicobrachial pain received ibuprofen 800
      mg/day, codeine 120 mg/day, or placebo during six 2 week periods. Clinical
      outcomes were assessed by pain diary, VAS of pain and change in pain, and
      uptime/downtime estimates. In none of the five subjects who completed the 12-week
      trial was analgesic efficacy of either drug shown. Major psychosocial and other
      medical influences on the subjects' status were encountered. The N-of 1
      methodology is appropriated for evaluating true efficacy of pharmacotherapy in
      patients with regional musculoskeletal pain.

PMID- 9601161
TI  - Comparison of the analgesic and intestinal effects of fentanyl and morphine in
      rats.
AB  - Clinical studies report a low incidence of intestinal side effects with
      transdermally administered fentanyl (TTS-fentanyl) in comparison with oral
      morphine. To support these clinical data, analgesic and intestinal effects of
      both opioids were compared in rats. After subcutaneous injection, analgesia in
      the tail withdrawal reaction test was obtained at a peak effect dose of 0.032
      mg/kg with fentanyl and 8.0 mg/kg with morphine. This analgesic dose exceeded the
      ED50 for inhibition of castor oil-induced diarrhea only slightly (1.1 x) in the
      case of fentanyl (0.028 mg/kg) but markedly (36 x) in the case of morphine (0.22
      mg/kg). To reverse completely the antidiarrheal effect of equivalent analgesic
      doses of the opioids (their ED50S for analgesia lasting 2 hours), much more
      naloxone was required in the case of morphine (5.4 mg/kg) than in the case of
      fentanyl (0.19 mg/kg). After oral administration, the difference between both
      opioids was less pronounced. Analgesia was obtained at 0.85 mg/kg with fentanyl
      and 32 mg/kg with morphine. This analgesic dose only slightly (1.7 x) exceeded
      the antidiarrheal dose in the case of fentanyl (0.49 mg/kg) but significantly
      (6.2 x) in the case of morphine (5.2 mg/ kg). To reverse completely the
      antidiarrheal effect of equivalent analgesic oral doses of the opioids (their
      ED50S for analgesia lasting 2 hours), more naloxone was required in the case of
      morphine (11 mg/kg) than in the case of fentanyl (2.0 mg/kg). Rapid penetration
      of fentanyl into the brain is thought to be responsible for small dissociation
      between the analgesic and intestinal effect of this lipophilic opioid. The
      present data provide preclinical evidence to support the relatively low incidence
      of intestinal side effects observed clinically with the use of TTS-fentanyl in
      comparison with orally administered morphine.

PMID- 9601163
TI  - Commentary: symptom management in children at the end of life.

PMID- 9601162
TI  - Case presentation: terminal sedation in a pediatric patient.

PMID- 9601164
TI  - Commentary: ethical issues in pediatric pain management and terminal sedation.

PMID- 9601165
TI  - Proceed with caution.

PMID- 9601166
TI  - Focal infection.

PMID- 9601167
TI  - Mouth and body.

PMID- 9601168
TI  - Hard as rocks.

PMID- 9601169
TI  - A characterization of first-generation flowable composites.
AB  - A plethora of new low-viscosity composite resin materials, or flowable
      composites, have been marketed during the last two years, but little has been
      published about them. The authors describe research in which they compared the
      properties--filler, depth or cure, flow, wear, compressive strength, diametral
      tensile strength, indented biaxial flexure strength and toughness--of flowable
      and hybrid composites. Mechanical property tests (ISO 4049, ISO/DIS 6872) of
      eight flowable composites and two hybrid composites were conducted. The flowable
      composite with the least flow was similar to traditional composites. Mechanical
      properties were generally about 60 to 90 percent of those of conventional
      composites. The authors conclude that flowable materials should be used with
      caution in high-stress applications for restorative dentistry.

PMID- 9601170
TI  - Knowledge, opinions and practices of general dentists regarding oral cancer: a
      pilot survey.
AB  - The authors mailed a pilot survey to 500 randomly selected general dentists.
      Although most dentists reported their knowledge of oral cancer to be current,
      their actual knowledge of oral cancer risk factors and signs and symptoms was
      inconsistent. Conflicting data were also found between their level of knowledge
      and their provision of oral cancer examinations. Most respondents agreed that
      patients should undergo an oral cancer examination annually, yet many do not
      provide this service.

PMID- 9601171
TI  - Caries prevention by CO2 laser treatment: dependency on the number of pulses
      used.
AB  - The aim of this study was to assess the caries-preventive potential of various
      carbon dioxide laser conditions and to explore the effect of the number of laser
      pulses used. The authors irradiated unerupted human molars at two wavelengths-
      10.6 or 9.6 micrometers--and at 1, 5, 25 or 100 pulses. All teeth were then
      subjected to pH cycling simulating the conditions for caries progression. Pulsed
      CO2 laser-preventive treatment inhibited caries-like lesion progression by up to
      87 percent. This effect was dependent on the number of pulses used, but there was
      no correlation between caries resistance and enamel surface morphological
      changes.

PMID- 9601172
TI  - Clinical success of class V composite resin restorations without mechanical
      retention.
AB  - The authors describe a study in which they placed 126 Class V composite resin
      restorations without mechanical retention, divided into three groups of 42, in 23
      patients. They followed the performance of the restorations over a three-year
      period. For all three groups, restorations were placed using All-Bond 2 dental
      adhesive and Z100 composite resin; A.R.T. Bond and Brilliant Dentin composite;
      and Prisma Universal Bond 3 and Variglass VLC polyacid-modified composite resin.
      The authors evaluated retention as well as color stability, wear resistance,
      sensitivity, sulcular depth, loss of attachment, bleeding on probing and
      crevicular fluid flow. Based on their results, the authors propose that
      restoration of Class V lesions without using mechanical retention could be
      expected to succeed in seven of 10 restorations over a three-year period using
      these restorative systems.

PMID- 9601173
TI  - Synthetic hair braid extension artifacts in panoramic radiographs.
AB  - The authors present two case reports that illustrate synthetic hair braid
      extension artifacts in panoramic radiographs. They found that hairstyles using
      synthetic hair braid extensions created radiopaque patterns that varied according
      to hairstyles. They discuss how these hair extensions may affect panoramic
      radiographs and the importance of determining whether patients are wearing
      synthetic hair braid extensions.

PMID- 9601174
TI  - The image of dentistry in contemporary culture.
AB  - The multimedia portrayals of dentists and dentistry have expanded in scope.
      Prevention and esthetics have replaced drilling and extraction in the public
      perception of dental practice. According to the author, dentists themselves are
      no longer treated exclusively as buffoons or sadists. Instead, he writes, they
      are more apt to be seen as solid citizens, occasionally as romantic figures and
      even as complex, realistic human beings.

PMID- 9601175
TI  - Dry brushing lingual surfaces first.

PMID- 9601176
TI  - Work force trends that influence dental service capacity.
AB  - Although the total number of active private dentists increased by 21.7 percent
      between 1982 and 1995, the number of active private part-time dentists increased
      by 104 percent, while the number of active private full-time dentists increased
      by 8 percent. Thus, the total number of hours active private dentists spent in
      the office has not increased to the same extent as the number of active private
      dentists. During the same period, however, the average number of hours spent
      treating patients increased, indicating that dentists are becoming more efficient
      in directing their office hours toward clinical dentistry. The distribution of
      active private part-and full-time dentists and the actual number of hours they
      spent in the dental office and spent treating patients provide a more complete
      picture of the capacity of the dental care delivery system than only looking at
      the increase in the total number of dentists.

PMID- 9601177
TI  - Latex case yields $1 million verdict.

PMID- 9601178
TI  - And we all lived happily ever after: understanding the biological controls of
      aging.

PMID- 9601179
TI  - Nosebleeds may mean something much more serious: an introduction to HHT.

PMID- 9601180
TI  - Advanced cancer.

PMID- 9601181
TI  - Chronic arsenic toxicity in west Bengal--the worst calamity in the world.
AB  - Since 1983 large number of people are being encountered with arsenic toxicity due
      to drinking of arsenic contaminated water (0.05-3.2 mg/l) in 6 districts of West
      Bengal. Clinical and various laboratory investigations were carried out on 156
      patients to ascertain the nature and degree of morbidity and mortality that
      occurred due to chronic arsenic toxicity. All the patients studied had typical
      rain drop like skin pigmentation (being inclusion criteria) while thickening of
      palm and sole were found in 65.5% patients. Other features included weakness
      (70%), gastro-intestinal symptoms (58.6%), involvement of respiratory system
      (57.08%) and nervous system (50.6%). Lung function tests showed restrictive lung
      disease in 53% (9/17) and combined obstructive and restrictive lung disease in
      41% (7/17) of patients. Abnormal electromyography was found in 34.8% (10/29) and
      altered nerve conduction velocity in 34.8% (10/29) of cases. Enlargement of liver
      was found in 120 cases (76.9%) while splenomegaly in 31.4% cases. Liver function
      test showed elevated globulin level in 15.8% and alkaline phosphatase in 51.3%,
      alanine amino transferase (ALT) in 11.8% and aspartate amino transferase (AST) in
      27.6% of cases. Evidence of portal hypertension was found in 33.3% patients.
      Liver biopsy reports of 45 patients showed non-cirrhotic portal fibrosis in 41,
      cirrhosis in 2 and normal histology in 2 cases. There was no correlation between
      the quantity of arsenic taken through water and the level of arsenic in hair,
      nail, liver tissues and the degree of fibrosis. There were 5 deaths of which one
      had skin cancer. The various non-cancer manifestations which were observed in
      these patients were much severe than those reported in similar cases in other
      parts of the world.

PMID- 9601182
TI  - Review of carcinoma cervix cases--epidemiological considerations.
AB  - One thousand six hundred ninety-four (1694) cases of carcinoma cervix have been
      reviewed out of a total of 11919 malignancies, over a period of 4 years (1992
      1995), in the department of radiotherapy, Safdarjung Hospital, New Delhi. The
      epidemiological features studied showed that there was a gradual decline in the
      total number of cases, age at presentation and parity. There has been a definite
      increase in the proportion of adenocarcinoma cases. Adenocarcinoma of cervix
      showed statistically significant preponderance in comparatively younger age group
      viz, 40-60 years (p < 0.005); 76% of overall cases were illiterate; 77% of cases
      belonged to rural/urban slum settings compared to 23% which were purely urban in
      origin. About 65% cases had haemoglobin levels below 10 g/dl at the time of
      presentation.

PMID- 9601183
TI  - A study of 70 cases of cutaneous metastases from internal carcinoma.
AB  - A retrospective analysis of 70 patients with metastatic cutaneous nodules, was
      conducted in the department of pathology, Kasturba Medical College, Mangalore.
      The available clinical records and histologic material of these cases were
      reviewed. In last few years fine needle aspiration cytology (FNAC) was being used
      as the main diagnostic tool. The commonest primary site of cutaneous metastasis
      in this study was gastro-intestinal tract (46.7%) in males and breast (32%) in
      females. Abdomen (including umbilical nodules) was found to be the most frequent
      site for metastatic cutaneous nodule.

PMID- 9601184
TI  - Evaluation of computed tomograms in paediatric head trauma.
AB  - Computed tomograms of 107 patients of head trauma in the paediatric age group
      were evaluated. Generalised brain swelling (44%) and falx sign (44%) were the
      commonest findings observed in the computed tomograms. The overall mortality was
      16.8% of which all except one were those with Glasgow coma scale between 3 and 7.

PMID- 9601185
TI  - Cryohaemorrhoidectomy for primary haemorrhoids: an evaluation of the procedure in
      the Indian population.
AB  - Cryotherapy is one of the available modalities for the management of primary
      haemorrhoids. It is a simple non-invasive procedure conducted without
      anaesthesia, ideal for surgery outpatients' department. Though practically given
      up in the west due to a distressing side-effect in the local population, it was
      evaluated for its efficacy and acceptability in the Indian population. The study
      of 174 patients revealed the procedure to be well accepted, extremely cost
      effective and with a low complication rate in the Indian population, in contrast
      to the western experience.

PMID- 9601186
TI  - Cutaneous malignant melanoma--clinical epidemiology and survival.
AB  - Melanoma of the skin is rare in the Asian population. However, this malignancy
      results in a high mortality due to the inadequacies in the referral pattern and
      management. India is one of the low incidence regions of the world. Cancer
      registries in India report that the age specific incidence rates for cutaneous
      malignant melanoma (CMM) are less than 0.5 per 1,000,000. There are only few
      reports in the literature on CMM in the Asian population. The Regional Cancer
      Centre at Trivandrum registers about 6000 new cancer cases per year and CMM forms
      0.5% of them. This paper presents the clinical epidemiology and survival of 79
      cases of CMM registered in the hospital cancer registry during the period 1985
      90. The peak age frequency was in the 7th decade. The male:female ratio was
      1.6:1. All cases had undergone a surgical manipulation in a peripheral centre,
      before being referred to this centre. This has posed limitation in staging and in
      deciding the extends of surgical excision. The overall 5-year survival rate was
      25.2% (95% confidence intervals, or, CI, 14%-38%). CMM in the low incidence
      regions may have a different aetiology and needs to be addressed in
      epidemiological studies.

PMID- 9601187
TI  - Familial tendency in hypersensitivity reactions to co-trimoxazole.

PMID- 9601188
TI  - Antiphospholipid syndrome--a distinct clinical entity.

PMID- 9601190
TI  - Diaphragmatic injuries in civilian practice.

PMID- 9601189
TI  - Primary carcinoma of fallopian tube after prolonged retention of Lippes loop.

PMID- 9601191
TI  - Is general surgery going the way of the dinosaur.

PMID- 9601192
TI  - What ails IMA?

PMID- 9601193
TI  - Pfiesteria!? An introduction.

PMID- 9601194
TI  - Fish lesions in the Chesapeake Bay: Pfiesteria-like dinoflagellates and other
      etiologies.
AB  - Ulcerative lesions and mass mortalities of Atlantic estuarine fish, particularly
      menhaden (Brevoortia tyrannus), have been associated with exposure to Pfiesteria
      like dinoflagellates and their toxins. We collected fish from the Chicamacomico
      River, Maryland, and observed solitary ulcerative lesions on the majority of
      menhaden sampled. One striped bass (Morone saxatilis) had an area of reddening
      around the base of the dorsal fin. Bluegill (Lepomis machrochirus), channel
      catfish (Ictalurus punctatus), yellow perch (Perca flavescens), and carp
      (Cyprinus carpio) were externally nonremarkable. Histologically ulcerative
      menhaden lesions demonstrated marked chronic inflammatory infiltrate in large
      areas of exposed necrotic muscle. The ulcers contained granulomata with fungal
      hyphae in the necrotic tissue. Gram negative rod-shaped bacteria were also
      observed in the lesions, a common finding in ulcers of aquatic organisms. Our
      data suggest that typical ulcerative lesions observed on fish from areas of
      Pfiesteria-like dinoflagellate blooms are reflective of dermatosis, which may be
      related to a variety of individual or combined environmental stressors. Exposure
      to dinoflagellate toxin)s) potentially represents one such stressor. The role of
      Pfiesteria-like dinoflagellate toxin in fish primary lesion development is
      currently under investigation.

PMID- 9601195
TI  - Strategies for environmental monitoring of toxin producing phantom
      dinoflagellates in the Chesapeake.
AB  - Toxin-producing estuarine dinoflagellates have been linked with the occurrence of
      fish kills and the development of a novel clinical illness syndrome among persons
      exposed to waters during fish kill events. The prototype organism of this group,
      Pfiesteria piscicida, has an extremely complex life cycle, making traditional
      methods used for environmental monitoring of harmful algal blooms less reliable.
      The response to fish kill events and the occurrence of human illness in Maryland
      in 1997 is reviewed, with particular emphasis on problems in organism detection.
      Current and anticipated classical and molecular methodologies for the detection
      of Pfiesteria and Pfiesteria-like organisms are reviewed. Development of these
      capabilities will be of critical importance in defining the epidemiology of human
      illness related to environmental exposure to Pfiesteria, and in developing public
      health strategies to predict and prevent such illness.

PMID- 9601197
TI  - Pfiesteria and the skin: a practical update for the clinician.
AB  - Skin complaints, including an episodic burning sensation on contact with river
      water, were common among 13 persons with exposure to Maryland's Pocomoke River in
      the summer of 1997. While the majority of findings on dermatologic examination
      were unrelated to toxic dinoflagellate exposure, a subset of patients
      demonstrated otherwise unexplained erythematous, edematous papules on the trunk
      or extremities. Histopathologic findings were suggestive of an inflammatory,
      toxic, or allergic process. It may be speculated that these otherwise unexplained
      cutaneous findings represent a cutaneous reaction to Pfiesteria or Pfiesteria
      like toxin; however, further evaluation of future affected persons will be
      warranted.

PMID- 9601196
TI  - Neurologic symptoms following Pfiesteria exposure: case report and literature
      review.
AB  - Although the recently identified dinoflagellate, Pfiesteria piscicida, may have
      neurotoxic effects on humans, the precise nature of the neurologic symptoms
      associated with varying levels of exposure is unknown. Toward this end, we review
      the neurologic symptoms of three Pfiesteria-exposed laboratory workers reported
      to data and compare them to the evaluation of an exposed waterman from Maryland.
      The occupational exposure of a Maryland waterman appears to produce a mild,
      reversible encephalopathy which predominantly affects functions associated with
      the frontal and temporal lobes. A comprehensive neurologic examination is
      recommended for all Pfiesteria piscicida and morphologically related organism
      exposed, symptomatic persons.

PMID- 9601198
TI  - Neurobehavioral complaints of symptomatic persons exposed to Pfiesteria piscicida
      or morphologically related organisms.
AB  - Over the next year, additional persons in Maryland may be at risk for exposure of
      toxic Pfiesteria or morphologically related organisms. These persons may present
      with a variety of memory and other behavioral complaints. This paper examines the
      kinds of complaints that persons with a documented Pfiesteria-related syndrome
      have compared to a nonexposed control group. The exposed group was more likely to
      report difficulties with concentration, forgetfulness, prospective memory, and
      information overload as well as feelings of confusion, bewilderment, and
      uncertainty as direct effects of toxin exposure. The exposed group was also more
      likely to report feeling uneasy, on edge, nervous, and shaky, which is probably a
      reaction to their newly acquired cognitive deficits and uncertainty about their
      recovery. In contrast, retrograde memory loss, disturbances of language or social
      behavior, depression, anger, hostility, or diminished activity levels are not
      symptoms that exposed persons are likely to report.

PMID- 9601199
TI  - Psychologic adjustment of watermen with exposure of Pfiesteria piscicida.
AB  - Preliminary study of the psychologic adjustment of watermen with exposure to
      Pfiesteria piscicida was conducted on watermen with the most severe exposures and
      their occupationally matched controls. Participants in the exposed group were
      seven symptomatic recreational and commercial fishermen who had direct exposure
      to the Pocomoke River or other estuarial waters on Maryland's Eastern Shore
      before, during, and/or after periods of documented fish kills and Pfiesteria
      activity. The control group included eight commercial fishermen who worked on the
      ocean side of the Eastern Shore and had no reported exposure to estuaries with
      documented Pfiesteria activity. Both exposed symptomatic and nonexposed watermen
      completed the Profile of Mood States to assess depression, anxiety, and other
      relevant mood states as part of their participation in the larger investigation
      of the human health effects of Pfiesteria piscicida. Preliminary results suggest
      that both exposed symptomatic and nonexposed watermen are psychologically healthy
      and exhibit what psychologists refer to as the classic Iceberg Mood Profile. The
      Iceberg Profile is characterized by endorsement of symptoms suggestive of high
      energy, enthusiasm and positive mood (e.g., lively, active, energetic, cheerful,
      vigorous, etc.) and relative minimization of symptoms suggestive of negative or
      depressed mood (e.g., tense, anxious, restless, grouchy, forgetful). Therefore,
      the Pfiesteria-related symptom complex documented in the exposed watermen cannot
      be explained by functional or psychiatric factors and is probably due to
      exposure.

PMID- 9601200
TI  - A critical review of the Pfiesteria hysteria hypothesis.
AB  - Mass hysteria or mass psychogenic illness is the spread of the belief of an
      illness (symptoms and the origins of the symptoms) through a population. The
      characteristics of mass psychogenic illness were reviewed and compared to the
      recent outbreak of human illness in the Pocomoke region in Maryland in the summer
      of 1997. The findings suggest that the nature of the symptoms complex--the onset
      and recovery course; the absence of secondary gain or job-related stress for most
      of the symptomatic persons; the predominance of males in the symptomatic group;
      and the baseline emotional stability of all persons examined--are inconsistent
      with the reported features of psychogenic illness in response to unknown
      environmental or chemical toxins. Although there may be individuals who exhibited
      hypochondriacal, hysterical, or other functionally based reactions, the recent
      outbreak of Pfiesteria-related illness probably does not represent an episode of
      mass psychogenic illness.

PMID- 9601202
TI  - Toxic-Pfiesteria--surveillance for human disease in Maryland.
AB  - The presence of toxic stages of the dinoflagellate Pfiesteria piscicida and other
      morphologically related organisms was documented in three estuarine waterways on
      the lower Eastern Shore of Maryland in 1997. The Maryland Department of Health
      and Mental Hygiene, working closely with the local health departments,
      established a surveillance system to collect reports of human illnesses.
      Maryland's experience has formed the base on which national surveillance criteria
      for Estuary Associated Syndrome have been developed and regional surveillance
      protocols have been built. The cooperation of practicing physicians is essential
      to continued surveillance efforts to further delineate the extent and nature of
      human health effects following exposures to waters where toxic forms of these
      dinoflagellates are active. Physicians wishing to report persons who may have
      Estuary Associated Syndrome should contact their local health department. Persons
      wanting information or wishing to report finding lesioned fish or a fish kill in
      progress should call the Maryland Pfiesteria Hotline at 1- 888-584-3110.

PMID- 9601201
TI  - Pfiesteria in Maryland: preliminary epidemiologic findings.
AB  - In the fall of 1996, fish kills in Maryland rivers were attributed to the
      dinoflagellate, Pfiesteria piscicida. After a group of researchers established a
      potential link between exposure to Pfiesteria and an illness causing memory
      problems, state health authorities closed a portion of the Pocomoke River. To
      determine the extent of illness, the range of symptoms, potential risk factors
      for disease, and to provide information to concerned citizens, a toll-free
      hotline was created. All symptomatic persons who called the toll-free number were
      administered a standardized questionnaire. Persons who had been exposed to
      Pfiesteria or Pfiesteria-laden waters were more likely to have respiratory,
      neurologic, dermatologic, and gastrointestinal problems than those persons
      without exposure. Among the persons calling the hotline, many had extensive
      neuropsychologic testing. Of the neuropsychologic test battery, low scores on the
      Rey Auditory Verbal Learning Test (RAVLT), a standardized measure of learning and
      memory, best characterized illness related to Pfiesteria exposure. Patients with
      low RAVLT scores were more likely to have neurologic symptoms and skin lesions
      than control subjects. Low RAVLT scores were associated with fishing (OR, 9.00,
      95% CI, 106, 409.87), catching fish with lesions (OR, 6.17, 95% CI 1.27, 32.10),
      and handling fish with lesions (OR, 5.34, 95% CI, 1.05, 29.92), but not with
      consumption of seafood. While preliminary, these results do suggest that some
      risk factors for Pfiesteria-related illness may be easy to modify and used to
      prevent unnecessary human exposure.

PMID- 9601203
TI  - Current status and future directions for the investigation and management of the
      human health effects of exposure to Pfiesteria piscicida or Pfiesteria-like
      dinoflagellates.

PMID- 9601204
TI  - Free-standing ambulatory surgical clinics.

PMID- 9601205
TI  - Release of patient records.

PMID- 9601206
TI  - Implementing advance directives.
AB  - Advance directives have an important place in medical practice. They promote
      planning for patients' medical care in unforeseen circumstances like
      unconsciousness from stroke or accident, when thinking and reasoning are impaired
      such as during a critical illness, and for patients facing death from conditions
      like terminal cancer or Alzheimer's Disease.

PMID- 9601207
TI  - Is there a union in your future?

PMID- 9601208
TI  - Patient-debtor collection practices.

PMID- 9601209
TI  - Michigan AIDS fund. A helping hand for patients.

PMID- 9601210
TI  - Easing cancer pain. New CD-ROM program provides help, answers for patients.

PMID- 9601211
TI  - Understanding and embracing multiculturalism in the health care arena.

PMID- 9601212
TI  - The future of managed care. Federal Patients' Bill of Rights.

PMID- 9601213
TI  - Births, marriages, divorces, and deaths for September 1997.

PMID- 9601214
TI  - Can a knowledge of anatomy save the NHS?

PMID- 9601215
TI  - Diagnostic tests for periodontal disease activity.
AB  - Destructive periodontal disease is found in a significant number of adult
      patients. At present there is no reliable method of determining the presence of
      active periodontal disease, other than retrospectively. Tests are being developed
      that rely on various markers of periodontal disease activity but all of those
      produced to date have limitations. It is to be hoped that reliable tests that can
      be used at the chairside will help the general dental practitioner to combat
      periodontal disease before it progresses too far.

PMID- 9601216
TI  - Ectopic teeth in the maxillary sinus: diagnosis and treatment.
AB  - Several types of developmental anomaly of the teeth have been identified. In this
      article the authors describe three patients who presented with impacted teeth in
      the maxillary sinuses.

PMID- 9601217
TI  - Should second molars be extracted?
AB  - The effect of removal of the first premolar on the facial profile is
      controversial, and some orthodontists prefer to extract the second permanent
      molar as an alternative. However, this procedure is not widely practised in spite
      of the many advantages claimed for it. The arguments for and against the
      technique are described here. Practising orthodontists should take all these
      arguments into account when planning treatment.

PMID- 9601218
TI  - Guidelines for taking radiographs of children.
AB  - Dental radiographs are required for monitoring many aspects of the dental care of
      children. This article reviews the current guidelines for taking dental
      radiographs of children, with particular reference to diagnosing caries,
      monitoring growth and development and managing trauma. There are a number of
      practical difficulties in taking radiographs of this age group, which are also
      discussed. The use of selection criteria to assist the clinician in choosing the
      optimal radiograph examination is recommended.

PMID- 9601219
TI  - The assessment and treatment of anterior open bite.
AB  - There is no single management strategy for dealing with open bites, which vary
      greatly in presentation and severity. The general dental practitioner is
      recommended to assess treatment need on whether the open bite is a problem to the
      patient: if it is not, then no remedial treatment may be required. To aid the
      practitioner in the often difficult decision-making process, in this paper the
      possible causes of open bite malocclusion are reviewed, together with the methods
      currently available for treatment of this condition and the uncertainties
      inherent in the prognosis. The need for treatment is also discussed, to assist
      the general dental practitioner in deciding as to whether referral is necessary.

PMID- 9601220
TI  - Letter from America.

PMID- 9601221
TI  - A study of the availability of emergency dental services in Birmingham.
AB  - The study reported here was undertaken to ascertain the efficiency and adequacy
      of the Emergency Dental Services in Birmingham. Even after the inception of the
      new contract in 1990, too many registered patients appeared to be attending the
      Birmingham hospitals or contacting their doctors for dental treatment which could
      and should have been provided by their own dentist. Overall, the results showed
      that the service provided by Birmingham dentists before 10.30 p.m. is more than
      adequate, and that most dentists are acting in accordance with the FHSA
      guidelines relating to the new contract.

PMID- 9601223
TI  - Dental CAD/CAM: a millstone or a milestone?
AB  - The number of dental computer-aided design/computer-aided manufacture (CAD/CAM)
      systems commercially available is growing. These systems range in complexity and
      application, from manual copy milling of inlays to full computer-controlled
      systems with a complex library of tooth forms enabling the automated production
      of crowns and bridges. All CAD/CAM systems permit the production of restorations
      at the chairside and, at least in theory, eliminate potential inaccuracies
      associated with the traditional, multistage production of indirect restorations.
      Their use also minimizes cross-infection. However, the capital costs of these
      systems are great and a high throughput of restorations is required in order to
      achieve financial viability. Long-term clinical studies are required before a
      final judgement may be made of the use of these relatively new systems.

PMID- 9601222
TI  - The use of cantilever bridges.
AB  - Replacement of missing teeth with fixed bridgework often involves producing full
      crown retainers on teeth on both sides of an edentulous space. Unfortunately,
      this approach can result in the destruction of much healthy tooth tissue, and the
      clinician must balance the benefits of replacing missing teeth with the amount of
      tooth preparation required. Current thinking in restorative dentistry places the
      preservation of tooth tissue at a premium, and most practitioners are happy to
      use techniques that embrace this philosophy. Because of this, cantilever bridges
      have an increasing role in dental practice, where the replacement for a missing
      tooth or teeth has one or more abutments on only one side of the edentulous
      space, being unsupported at the other. Cantilever bridges fall into several
      types, depending on the number of abutments and types of retainers. This article
      describes the various cantilever bridge designs, considers the biomechanics of
      these restorations, and provides guidelines for their clinical use.

PMID- 9601224
TI  - Surgical access to an impacted lower third molar by sagittal splitting of the
      mandible: a case report.
AB  - It is well documented that surgical removal of an impacted mandibular third molar
      may damage the inferior alveolar nerve. Assessing the likelihood of injury
      depends to a great extent on preoperative radiographic examination, to determine
      the proximity of the tooth to the nerve. If the nerve and tooth are closely
      related the roots should be divided and removed separately. In the case reported
      here, elective sagittal splitting of the mandible was used to gain access to an
      impacted lower third molar, which was intimately involved with the inferior
      alveolar nerve.

PMID- 9601225
TI  - Anxious children: coping in dental practice.
AB  - Treating anxious children is a challenge that many dentists face. Not only do
      anxious children find it difficult to cope with dental treatment but dentists
      also find it difficult to cope with anxious children. This article is intended to
      simplify the management of anxious children in general dental practice.
      Behavioural management, the coordination of the whole dental team, treatment
      planning and the use of inhalation sedation will be discussed.

PMID- 9601226
TI  - Speech-language pathologists' knowledge of, exposure to, and attitudes toward
      oral myofunctional phenomena.
AB  - A questionnaire developed by the authors was completed by 75 experienced speech
      language pathologists from varied work settings. Questions dealt with knowledge,
      attitudes and experience in the area of oral myofunctional disorders. Only 18
      respondents listed their classroom instruction in this area as adequate; only six
      related their practicum experience as adequate. In spite of the limited training
      reported by the clinicians, 32% were actively providing treatment for clients
      with oral myofunctional disorders. There was general agreement concerning the
      importance of training in this area.

PMID- 9601227
TI  - Treating orofacial dyskinesia with functional physiotherapy in the case of
      frontal open bite.
AB  - Oral myofunctional therapy was found to be successful, in a group of 75 patients,
      ages six to 22 all with anterior open bites. Seventeen of 19 who lisped before
      therapy eliminated the lisp. Upper respiratory system allergies were eliminated
      in nine of 11 patients. A combination of myofunctional therapy and orthodontic
      treatment was more successful in correcting lip resting posture than was therapy
      alone. Lip and tongue resting postures, along with swallowing patterns, were
      corrected to a highly significant degree.

PMID- 9601228
TI  - Orthodontic changes in oral dyskinesia and malocclusion under the influence of
      myofunctional therapy.
AB  - 28 patients in an orthodontic practice who demonstrated both characteristic
      malocclusion forms with deficiency in the sagittal, transverse and vertical
      dimensions and orofacial dyskinesia of the inner and outer circles were divided
      according to clinical criteria into two therapy groups within the framework of a
      pilot study. One group was treated exclusively with myofunctional therapy, the
      other with myofunctional therapy and orthodontic appliances (for example
      activators). Specific examination and goal parameters were documented at the
      commencement and the conclusion of therapy.

PMID- 9601229
TI  - Open mouth posture and cross-sectional nasal area in young children.
AB  - A biracial sample of two-hundred ninety-six children were assessed for open-mouth
      posture (OMP) in the natural environment. In addition, rhinometry was performed
      on 288 of the youngsters. Means were computed for percent OMP and cross-sectional
      nasal airway. Results indicated that in general these children exhibited
      relatively high rates of OMP. Boys displayed significantly greater OMP than
      girls. However, children exhibiting OMP on 80% of the observation intervals had
      significantly smaller cross-sectional nasal areas than the youngsters who
      displayed OMP on fewer than 20% of observation intervals. The implications of the
      findings were discussed.

PMID- 9601230
TI  - Oral myofunctional therapy in Argentina.

PMID- 9601231
TI  - The Castillo-Morales approach to orofacial pathology in Down syndrome.
AB  - Infants with Down syndrome often present with a familiar orofacial disorder which
      exists at birth or becomes more pronounced by the end of the first year. The
      primary pathology includes hypotonicity of the perioral muscles, lips, and
      masticatory muscles and a protruding tongue, later followed by active tongue
      protrusion. This results in problems with sucking, swallowing, drooling and
      dentition. Early intervention methods employing the combination of Castillo
      Morales Manual Orofacial Therapy and his specially designed palatal plate, can
      improve orofacial function, facial appearance and prevent secondary conditions
      like pseudoprognathism, dental diseases, malocclusions, open mouth habit and
      pseudomacroglossia. This retrospective study examines the outcome of therapy, as
      prescribed by Castillo-Morales, in 39 children with Down syndrome. Normally, the
      average age to begin oral therapy is between six to eight months. The children
      were treated with the Castillo-Morales Manual Orofacial Therapy and his palatal
      plate for an average of 17.9 months. In this study, clinical evaluations at the
      beginning and the end of therapy focused only on open mouth posture and tongue
      protrusion. In addition, the direct stimulating effect of the palatal plate on
      tongue protrusion was evaluated. Significant positive results were observed in
      all three areas.

PMID- 9601232
TI  - Tooth movement associated with orofacial myology from a dental hygiene
      clinician's perspective.

PMID- 9601233
TI  - Mixed dentition analysis: a review of methods and their accuracy.
AB  - Methods that have been proposed for mixed dentition analysis are reviewed.
      Prediction of the space required in the dental arch for unerupted permanent
      canines and premolars has been based either on the correlation between the mesio
      distal widths of these teeth and of erupted mandibular incisors, or on
      measurements of the unerupted teeth on radiographs. Studies comparing the
      different methods have shown that the method of Hixon & Oldfather (1958), as
      refined by Staley & Kerber (1980), is the most accurate.

PMID- 9601234
TI  - Dental caries, tooth trauma, malocclusion, fluoride usage, toothbrushing and
      dietary habits in 4-year-old Swedish children: changes between 1967 and 1992.
AB  - The dental health of 4-year-old children in the city of Umea, northern Sweden,
      has been followed in cross-sectional studies conducted in 1967, 1971, 1976, 1980,
      1987 and 1992. Similar methods and criteria were used. Dental caries and
      background factors (fluoride usage, toothbrushing frequency and diet) were
      recorded. In 1971, 1987 and 1992 signs of tooth trauma and presence of
      malocclusion were also recorded, the latter also in 1976. The present paper
      summarizes the results of these studies. Between 1967 and 1992 the mean dmfs
      values declined from 7-8 to 1-8. The decline was greatest between 1967 and 1980
      and then levelled off. Toothbrushing frequency was similar over the years, but
      parental help with brushing was more common in the more recent studies. The use
      of fluoride toothpaste increased. About 30% of the children had experienced tooth
      trauma. A unilateral crossbite was recorded in 18% and 16% of the children in
      1971 and 1992, respectively, and an anterior open bite in about 35% and 41%,
      respectively; both types of malocclusion were related to a dummy- or finger
      sucking habit.

PMID- 9601235
TI  - Dental caries and prolonged breast-feeding in 18-month-old Swedish children.
AB  - Three thousand children aged 18 months were screened for dental caries and
      ongoing breast-feeding at 46 child welfare centres in different parts of Sweden.
      Of these, 200 children were selected for a more comprehensive examination,
      involving investigation of dietary, toothbrushing and sucking habits, use of
      fluoride, and determination of salivary levels of mutans streptococci and
      lactobacilli. The children were divided into four groups: group 1: children with
      caries not being breast-fed; group 2: children with caries being breast-fed;
      group 3: caries-free children being breast-fed; group 4: caries-free gender- and
      age-matched reference children not being breast-fed. The results showed that 63
      of the children (2.1%) had caries and 61 (2.0%) were still being breast-fed.
      Twelve (19.7%) of the 61 children still being breast-fed had caries compared with
      51 (1.7%) of the 2939 children not being breast-fed; the difference was
      statistically significant. Children with caries and still being breast-fed had a
      mean defs of 5.3, and those with caries not being breast-fed 4.9; the difference
      was not statistically significant. Children with caries, irrespective of whether
      they were being breast-fed or not, had significantly higher numbers of cariogenic
      food intakes per day than caries-free children. Mutans streptococci were detected
      in 67% of the children and lactobacilli in 13%. Children with detectable mutans
      streptococci and lactobacilli had significantly more caries than those without.
      The results indicate that Swedish children with prolonged breast-feeding have a
      tendency to establish unsuitable dietary habits which constitutes a risk
      situation for developing caries at an early age.

PMID- 9601236
TI  - High-volume aspiration as a supplemental scavenging method for reducing ambient
      nitrous oxide levels in the operatory: a laboratory study.
AB  - Occupational exposure to low levels of nitrous oxide (N2O) have been associated
      with adverse health effects. The National Institute for Occupational Safety and
      Health has established a threshold guideline of 25 ppm N2O. The purpose of this
      laboratory study was to determine the effectiveness of a high-volume dental
      aspirator as a supplemental device to reduce ambient N2O levels in the operatory.
      The investigation evaluated four experimental groups that were assigned based on
      whether or not the aspirator was used and on the rate at which operatory
      ventilation was established (5 or 10 room air exchanges per hour). Ambient N2O
      levels were monitored at 30 cm from the nasal hood using an infrared
      spectrophotometer. The room air exchange rate was measured with a flow hood and
      then manipulated to the desired ventilation rate. N2O levels were detected with a
      spectrophotometer and data were recorded with a microprocessor that continuously
      collected data. The results demonstrated that both utilization of supplemental
      oral aspiration and increased operatory ventilation significantly reduced ambient
      N2O levels. It was concluded that a high-volume aspirator, when used in
      conjunction with the normal scavenging system, can significantly reduce ambient
      N2O levels to within the guidelines established by the National Institute for
      Occupational Safety and Health.

PMID- 9601238
TI  - Dental caries experience of children in remission from acute lymphoblastic
      leukaemia in relation to the duration of treatment and the period of time in
      remission.
AB  - The dental condition of 54 children aged 3-19 years who were in remission from
      acute lymphoblastic leukaemia was examined in relation to the duration of their
      chemotherapy and their period of time in remission. There were no significant
      differences in the number of early ('white spot') lesions or in the total dental
      caries experience in relation to the duration of chemotherapy. Children who were
      longest in remission had significantly more white spot lesions in permanent teeth
      but not in primary teeth, and there was no significant difference in dental
      caries experience. Children who had received nystatin treatment for more than a
      year had significantly more white spot lesions in permanent teeth than those who
      had received nystatin for shorter periods.

PMID- 9601237
TI  - The prevalence of clinically significant anaemia and haemoglobinopathy in
      children requiring dental treatment under general anaesthesia: a retrospective
      study of 1000 patients.
AB  - There is little information on the possible value of screening children who are
      liable to haemoglobinopathies as part of pre-operative assessment for dental
      treatment under general anaesthesia. The present retrospective investigation
      examined, first, the number of patients having low haemoglobin levels among 1000
      patients who had undergone haematological investigation prior to general
      anaesthesia in a dental outpatient unit, and, secondly, the subsequent clinical
      management of these patients. Haemoglobin levels of 10.0 g/dl or less were found
      in 31 children: 13 Asian, 7 Afro-Caribbean, 5 Mediterranean, 3 Arabic, 1 white
      Caucasian and 2 Oriental children. In addition, 17 patients had sickle-cell trait
      and 2 had beta-thalassaemia trait, but there was no relationship between the
      presence of haemoglobinopathy and low levels of haemoglobin. The planned general
      anaesthesia was undertaken for 22 of the 31 children who had low levels of
      haemoglobin and for the 19 children with haemoglobinopathy. Only 6 children
      ultimately did not undergo general anaesthesia, all failing to return. It is
      concluded that pre-anaesthetic haematological assessment of children needing
      minor dental surgery is rarely of any significant clinical value.

PMID- 9601239
TI  - Primary Sjogren's syndrome and rampant dental caries in a 5-year-old child.
AB  - A 5-year-old boy of Pakistani parents first presented with rampant dental caries
      and later developed bilateral parotid gland enlargement accompanied by
      intermittent nocturnal fever, anorexia, lethargy and weight loss. Investigations
      revealed anaemia, hypergammaglobulinaemia, elevated non-specific indices of
      inflammation, a reduced Schirmer's test value, lymphocytic infiltration and some
      atrophy of the parotid gland. The parotid gland enlargement, low Schirmer's test
      value and salivary gland biopsy showing non-focal lymphocytic infiltration led to
      the diagnosis of primary Sjogren's syndrome. The present case report highlights
      the need for health professionals to be aware that Sjogren's syndrome is a
      possible, if rare, predisposing cause of rampant dental caries in children.

PMID- 9601240
TI  - Oral myiasis: report of two cases.
AB  - Case reports are presented of two patients from Oman who developed myiasis in the
      palate. Both suffered from cerebral palsy and had incompetent lips, anterior open
      bite and very poor oral hygiene. Both patients had denuded areas of hard palate
      anteriorly. In both cases large numbers of maggots were found under the
      surrounding mucoperiosteam. Removal of the maggots and debridement resulted in
      resolution of the condition.

PMID- 9601241
TI  - Ameloblastic fibroma: report of two cases.
AB  - The ameloblastic fibroma is an odontogenic tumour with an unusual presentation.
      It is considered to have both epithelial and mesenchymal elements, but it lacks
      any calcified dental structures. Two new cases are presented. The first of these
      began as a mandibular tumour whereas the second was discovered by chance. The
      radiographic finding in each case was a unilocular cystic radiolucency. Treatment
      consisted of excisional biopsy by enucleation in both patients. Histopathological
      findings were consistent with ameloblastic fibroma.

PMID- 9601242
TI  - Oral-health-related knowledge and behaviour of a group of 15-year-old school
      children from Damascus, Syria.

PMID- 9601243
TI  - Fixed bonded prosthodontics: a 10-year follow-up report. Part I: Analytical
      overview.
AB  - Developments in biomaterials in the field of adhesion have made possible a less
      invasive dentistry. Improvements in adhesive polymers along with the analysis of
      certain failures in resin-bonded prostheses have suggested the micropreparation
      of abutment teeth. A long-term study of resin-bonded prostheses and splints was
      undertaken. The success rate of this protocol is presented for a study period of
      10 years (1984 to 1993). These results indicated that the resin-bonded prosthesis
      is a viable option in patients who are missing one or two teeth. Of 145
      prostheses, 11 failed, resulting in an overall survival rate of 83% (Kaplan-Meier
      test). Furthermore, the study confirmed that, for splints, preparation is
      important to counter the major stresses related to tooth mobility in patients
      with periodontal disease.

PMID- 9601244
TI  - Bone augmentation at single-tooth implants using mandibular grafts: a one-stage
      surgical procedure.
AB  - The surgical procedure of using a titanium implant in combination with a
      mandibular bone graft for a single-tooth reconstruction is presented. The donor
      bone was taken from the vestibular base, close to the symphysis of the mandible.
      Patients who were missing a maxillary incisor or canine tooth, and exhibiting a
      loss of supporting bone in the area, were found suitable for the technique.

PMID- 9601245
TI  - Guided tissue regeneration using a biodegradable barrier membrane for new
      attachment: a clinical, histologic, and histometric study in dogs.
AB  - Although nonbiodegradable barrier membranes have proven partially successful in
      achieving regeneration of lost periodontium through the principles of guided
      tissue regeneration, their use requires a second surgical procedure for their
      removal. The results of a study, in which a biodegradable collagen membrane was
      used to treat dehiscence defects in dogs, are presented. The membrane was an
      effective barrier to the downgrowth of gingival epithelium during the early
      stages of healing and tended to increase the regeneration of new cementum and
      connective tissue attachment. It was also biocompatible and biodegradable.

PMID- 9601246
TI  - Modified coronally positioned flap for obtaining new attachment in Class 2 and 3
      furcation defects. Part I: Rationale and surgical technique.
AB  - A new technique, the modified coronally positioned flap procedure, is described
      for treatment of Class 2 and Class 3 molar furcation defects in conjunction with
      barrier membranes. This technique is designed to minimize barrier exposure during
      the healing phase and to cover and protect the newly formed granulation tissue
      following barrier removal. Examples are presented and discussed, and
      modifications for varying situations are described. The modified coronally
      positioned flap technique is applicable for use with nonresorbable and resorbable
      membranes.

PMID- 9601247
TI  - Inferior alveolar nerve repositioning in implant dentistry: a preliminary report.
AB  - The surgical repositioning of the inferior alveolar nerve facilitates the
      placement of implants in the posterior mandible. The entire height of the
      posterior mandible is made available and enables implants to be anchored in two
      cortical plates, improving the primary fixation and increasing the area of the
      bone-implant interface. The posterior mandible can thus be predictably treated
      with implants in those cases where posterior support is considered important for
      occlusal stability and masticatory efficiency. The rapid and total recovery of
      sensation to the lip following nerve repositioning renders the procedure more
      acceptable to both the patient and the clinician.

PMID- 9601248
TI  - A new copolymerized composite resin system: a multiphased evaluation.
AB  - Most microfilled composite resins are relatively resistant to generalized wear;
      however, they commonly exhibit poor resistance to localized wear because of
      debonding of prepolymerized particles from the resin matrix. A copolymerized new
      composite resin, in which the filler particle trimethylolpropane-trimethacrylate
      is chemically bonded to the resin matrix, is evaluated. Epic-TMPT was subjected
      to both generalized and localized wear tests that revealed that its wear
      resistance was higher than that of other composite resin systems. Epic-TMPT in
      posterior occlusal cavities showed less than 8 microns of wear for each
      restoration, 1 year after placement. Placement of Epic-TMPT into large anterior
      abfraction lesions without mechanical retention, with surface etching, and
      subject to severe traumatic occlusion resulted in 87% retention 1 year after
      placement. In vivo usage biocompatibility tests demonstrated no pulpal irritation
      or inflammation when Epic-TMPT was placed on vital dentin of crown preparations
      with complete enamel removal.

PMID- 9601249
TI  - Histologic evaluation of alveolar bone following CO2 laser removal of connective
      tissue from periodontal defects.
AB  - This study was undertaken to examine histologically the healing response of
      alveolar bone following removal of granulation and/or connective tissues from
      interproximal craters by manual curettage or ablation by carbon dioxide laser.
      The time required to complete each type of degranulation procedure was also
      compared. Four interproximal treatment sites in each quadrant of two dogs were
      randomly assigned to each treatment modality. Neither treatment modality was
      totally effective in removing all suprabony connective tissue. Healing was
      clinically uneventful and histologically similar for both treatment groups at all
      time intervals. Laser-treated specimens exhibited little or no inflammatory cell
      infiltrate, areas of heat-induced tissue necrosis, accumulations of carbonized
      debris that initially was surrounded by macrophages and eventually phagocytized
      by multi-nucleated giant cells, and spicules of nonvital bone that exhibited a
      surface layer of osteoid. Although manual curettage was found to be statistically
      significantly faster, the difference between mean times was roughly 55 seconds
      and therefore unlikely to be clinically significant.

PMID- 9601250
TI  - The new In-Ceram Spinell system--a case report.
AB  - The final color of all-ceramic restorations is mainly dependent on the light
      transmission characteristics of the different components of the ceramic material.
      This article is a report on the improvement in light reflection and light
      transmission possible with the new In-Ceram Spinell crown system, which provides
      a natural-looking appearance.

PMID- 9601251
TI  - "Collagen adhesion" revisited.
AB  - Histologic studies of periodontal reconstructive therapies have repeatedly shown
      a zone of nondescript connective tissue adaptation, or collagen adhesion, to the
      root surface between the apical extension of the junctional epithelium and the
      coronal extension of identifiable regenerated cementum. To clarify the nature of
      this zone, supra-alveolar periodontal defects were created bilaterally in the
      mandibular premolar region in three beagle dogs, and exposed roots were
      instrumented to remove the cementum. Flaps were then coronally advanced and
      sutured. Histologic analysis after 12 weeks of healing showed instrumented root
      dentin not associated with junctional epithelium, new cementum, root resorption,
      or ankylosis in 27 of 60 root surfaces. In 10 of these specimens subsequently
      examined by transmission electron microscopy, collagen fibrils were generally
      oriented parallel to and in close proximity to the root. A mechanism of collagen
      attachment was, in fact, functioning at sites of collagen adhesion; these areas
      may validly be included in the histologic attachment level reported in studies of
      periodontal reconstructive therapy.

PMID- 9601252
TI  - Transplantation of a preosseointegrated implant from the mental area to a
      maxillary sinus graft.
AB  - When maxillary sinus grafting is performed to allow placement of fixed
      restoration in edentulous posterior sites, standard procedures involve placement
      of the sinus graft and then, after a graft-maturing time, placement of implants,
      which must osseointegrate before they can be used to support a restoration.
      Transplantation of a preosseointegrated implant from the mental area to the graft
      site may be preferable to standard two-step procedures. Advantages of the
      transplant procedure include reduction in total treatment time, a more
      predictable therapeutic outcome, and, it appears, improved bone quality,
      configuration, and retention around the implant.

PMID- 9601253
TI  - Postoperative healing complications associated with Gore-Tex Periodontal
      Material. Part II. Effect of complications on regeneration.
AB  - The gain in open probing attachment level as a result of a guided tissue
      regeneration procedure with Gore-Tex Periodontal Material was measured in 62
      sites. The incidence of complications was evaluated. When sites with a
      complication were compared to those without the complication, there was no
      statistically different gain or loss of newly regenerated tissue. However, the
      occurrence of sloughing of the gingival flap decreased the amount of gain in open
      probing attachment level. Analysis of the data also revealed that the combined
      use of allografts and a delay in the removal of the Gore-Tex Periodontal Material
      had a synergistic positive effect on the gain in open probing attachment level.
      No association between these treatment variables and the incidence of the
      complications was found.

PMID- 9601254
TI  - Histologic evaluation of osseointegrated implants restored in nonaxial functional
      occlusion with preangled abutments.
AB  - Of concern with the use of preangled abutments on implants is the transmission of
      masticatory forces and the angle at which they occur. Nineteen endosseous
      implants were placed in two subhuman primates. After 6 months, to allow for
      osseointegration, the implants were fitted with preangled abutments of various
      degrees and restored with type IV alloy castings. Straight abutments were used as
      control. Histologic evaluation revealed that, after 1 year of service, the
      implants exhibited complete osseointegration. Implants, whether restored with
      straight or preangled abutments, had no adverse effect on the surrounding bone.
      Soft tissue pockets measured, on average, from 2.2 to 2.6 mm; acute and chronic
      inflammatory cells were present. When crown loss was observed, it was caused by
      mechanical failure of components, such as gold screws and the screws used to
      secure the preangled abutments to the implants. Preangled abutments appear to be
      a valuable adjunct in implant dentistry, although long-term studies are needed
      for confirmation.

PMID- 9601255
TI  - Periodontal healing after guided tissue regeneration with Atrisorb barriers in
      beagle dogs.
AB  - Periodontal healing after use of Atrisorb barrier material (polylactic acid) for
      guided tissue regeneration was studied in the premolar and molar teeth of six
      beagle dogs. Defects studied were surgically induced or were caused by naturally
      occurring periodontitis. Barriers fragmented and became displaced in 2 to 5 weeks
      after application. Granulation tissue was sometimes present between the barrier
      and root surface at 10 days to 4 weeks. Several sites were surgically reentered
      at 4 months, and new bone covered 60% to 100% of the formerly exposed furcations
      and root surfaces. Sites obtained for histologic evaluation 9 to 12 months after
      the baseline surgery showed new connective tissue attachment, cementum, and
      alveolar bone. Histomorphometric analyses quantitated these tissue changes, and
      new connective tissue attachment covered 72% of surgically exposed root surfaces
      and 77% of periodontitis-exposed root surfaces. It was concluded that new
      periodontal supporting tissues became reconstituted on root and furcation
      surfaces after use of the Atrisorb barrier material for GTR.

PMID- 9601256
TI  - Gingival recession and exposure of barrier membrane: effect on guided tissue
      regeneration of Class II furcation defects.
AB  - The purpose of the present study was to evaluate the effect of barrier membrane
      exposure on the success of guided tissue regeneration in Class II furcation
      defects. Twenty-six subjects with mandibular Class II furcation defects received
      initial periodontal therapy followed by guided tissue regeneration surgery. The
      membrane was placed and the flaps were repositioned so that the membrane was
      totally submerged. Membranes were removed 4 to 6 weeks later, at which time the
      extent of their exposure was recorded. An overall improvement in all clinical
      parameters was observed for all subjects 1 year after surgery. Half of the
      patients had experienced no membrane exposure, while the other 13 subjects had
      experienced mild to pronounced exposure; both groups showed similar improvement
      in all clinical and surgical parameters. In light of the comparable results
      obtained in exposed sites, and the anatomic difficulties sometimes encountered in
      covering a membrane completely, in some of these cases the membrane may be left
      only partially submerged. This approach will allow for tighter occlusal "seal" of
      the tooth-membrane interface and preservation of the keratinized gingiva.

PMID- 9601257
TI  - Obstructive sleep apnea, the dentist and two case reports.

PMID- 9601258
TI  - Every patient deserves a good fit.

PMID- 9601259
TI  - The Dental Patient Assurance Act. TDA Council on Governmental Affairs.

PMID- 9601260
TI  - Keep your patients for life!

PMID- 9601261
TI  - Age of debts affects their collectible value.

PMID- 9601263
TI  - Practice sale handled by office manager.

PMID- 9601262
TI  - Windows for telescopes and implant abutments.

PMID- 9601264
TI  - Are your instruments sterile?

PMID- 9601265
TI  - Options in major medical coverage for Texas dentists and their employees.

PMID- 9601266
TI  - A view of the profession: from dental student to practitioner--a 10-year
      perspective.

PMID- 9601268
TI  - Outgoing president's message.

PMID- 9601267
TI  - Panama. Dentists and dental students volunteer in Panama.

PMID- 9601269
TI  - Periodontal treatment alternatives.

PMID- 9601270
TI  - Finding a financial coach.

PMID- 9601271
TI  - Incoming president's message.

PMID- 9601272
TI  - Highlights of updated recommendations by the American Heart Association (AHA) for
      the prevention of bacterial endocarditis.

PMID- 9601273
TI  - Results of the Texas Dental Association's dental hygiene needs survey.

PMID- 9601274
TI  - Helpful hints for getting paid at time of treatment.

PMID- 9601275
TI  - Children, changes and challenges.

PMID- 9601276
TI  - Why do 20% of our children experience 80% of the decay? An update on the status
      of childhood caries.

PMID- 9601277
TI  - First dental visit, first birthday: a rationale and protocol for infant oral
      health care.

PMID- 9601278
TI  - For a limited time only! Or treatment of temporary teeth in tots.

PMID- 9601279
TI  - Soothing the savage small-fry: a sampler of behavior management techniques.

PMID- 9601280
TI  - Dental treatment for the medically compromised pediatric patient: just the facts.

PMID- 9601281
TI  - A summary of facts about child abuse/neglect.

PMID- 9601283
TI  - Internet: the basics.

PMID- 9601282
TI  - DIY guide to primary tooth trauma repair.

PMID- 9601284
TI  - A dentist navigates "the net".

PMID- 9601285
TI  - List of interesting dental sites on the Internet.

PMID- 9601286
TI  - The power of E-mail takes author's voice across the globe.

PMID- 9601287
TI  - TDA Web site in words and pictures.

PMID- 9601289
TI  - Seller financing of practice sale.

PMID- 9601288
TI  - Enteral and parenteral conscious sedation to control pain and anxiety in
      periodontics.

PMID- 9601290
TI  - Treating needlestick injuries from HIV-positive patients always imperative.

PMID- 9601291
TI  - Guided tissue regeneration in surgical endodontics: improving the prognosis of
      periradicular surgery.

PMID- 9601292
TI  - Restoring endodontically treated teeth.

PMID- 9601293
TI  - Management of pain in endodontic patients.

PMID- 9601294
TI  - Achieving profound anesthesia using the intraosseous technique.
AB  - The intraosseous technique has been described as a useful adjunct to primary
      anesthetic administration. It has several advantages (Table 3) over other
      supplemental techniques in that it is relatively simple to implement into routine
      practice, it affords fast, predictable results, and it is relatively painless.
      The technique has been shown to be very successful in achieving profound pulpal
      anesthesia when administered as a supplement to the inferior alveolar nerve block
      and is effective in achieving profound anesthesia in irreversibly inflamed teeth,
      especially mandibular molars.

PMID- 9601295
TI  - Endodontic retreatment.

PMID- 9601296
TI  - Advances in endodontic surgery.

PMID- 9601297
TI  - Root canal preparation.

PMID- 9601298
TI  - New drugs and drug products approved in 1996.

PMID- 9601299
TI  - In-house peer review: the writing support group.

PMID- 9601300
TI  - A diminishing of self: women's experiences of unwanted sexual attention.
AB  - The health effects of everyday occurrences of unwanted sexual attention (such as
      looks, whistles, and comments) were explored in semistructured interviews with 8
      women in Seattle, WA. Participants described the strategies they used for
      avoiding and dealing with unwanted sexual attention, as well as the effects the
      attention had on their health and sense of self. Grounded theory techniques were
      used to code the data and identify themes. The women in this study were affected
      both physically and emotionally by their experiences and their perceived
      ineffectiveness in dealing with them. On a phenomenological level, these
      experiences contributed to a "diminishing of self," which included feeling
      dehumanized and lacking agency. This project begins to describe the complexities
      of this seemingly simple everyday occurrence and relates the experience to social
      science and psychological theory.

PMID- 9601301
TI  - Lesbians and cancer support: clinical issues for cancer patients.
AB  - In this article, I discuss clinical issues addressed while conducting support
      groups for lesbians with cancer. For group participants, issues relating to
      sexual orientation affected comfort levels with treatment interventions,
      communication with health care providers, ability to obtain emotional support,
      and coping. For example, assistance in information processing, decision making,
      and emotional support during treatment are typically provided by spouses of
      individuals with cancer. However, many women reported experiencing additional
      anxiety because of their decision to reveal their sexual orientation to medical
      providers. Fear of stigmatization and the possibility of compromised care
      contributed to anxiety about disclosure of sexual orientation. Whenever possible,
      differences in women's experiences based on race are also highlighted. The
      findings can begin to inform our assessment, problem conceptualization, and
      treatment approaches for lesbians with cancer.

PMID- 9601302
TI  - Living in two worlds: Native American women and prenatal care.
AB  - The purpose of this qualitative study was to explore traditional beliefs and
      practices related to pregnancy and childbirth among Native American women and
      examine the relationship of these beliefs and practices to current use of
      prenatal care. Focus groups of elders and young women were held and the data
      analyzed with the Ethnograph software. The central theme was the breakdown in
      transmission of cultural wisdom among Native American women. The major causes
      described by women were federal assimilation policies and deaths of elders. Major
      factors influencing young women's nonutilization of prenatal care were this
      breakdown, the "Western model" of prenatal care, substance abuse, and domestic
      violence. Recommendations for improving the use of prenatal care are grounded in
      the reality that Native American women live in two different worlds. Prenatal
      care should be reconceptualized as traditional cultural wisdom, with the majority
      of care provided by natural helpers in the Native American community, including
      tribal elders, grandmothers, and aunts in collaboration with licensed providers.

PMID- 9601303
TI  - Quality of life in women with heart failure.
AB  - Persons with heart failure (HF) experience impaired quality of life (QOL).
      However, the majority of research conducted on QOL in persons with HF has been
      with men. The purpose of this descriptive pilot study was to describe the impact
      of symptoms of HF and examine the relationships among symptom impact, perceived
      health status, perceived social support, and overall QOL in 30 women who had
      recently been hospitalized for HF. The women reported high physical symptom
      impact, poor perceived physical health status, and impaired QOL. Physical symptom
      impact, perceived physical health status, and QOL were moderately to highly
      correlated with one another. Perceived social support was significantly, though
      not strongly, correlated with physical symptom impact. Emotional symptom impact
      and mental health status were significantly and negatively correlated with each
      other but were not significantly correlated with QOL. In this group of 30
      chronically ill women, QOL was lower in those women who reported greater physical
      symptom impact and poorer perceptions of their physical health status.

PMID- 9601304
TI  - Maternal-child health in Zimbabwe.
AB  - In this paper I describe maternal and child health needs in Zimbabwe, as well as
      existing health care delivery services designed to meet these needs. The
      information presented is based on a project sponsored by Earthwatch (a worldwide
      volunteer organization) that addressed the needs of women and infants, as well as
      the author's contribution to this effort. Because of a long-standing drought,
      many women and children in Zimbabwe are malnourished. Poor nutrition affects the
      woman herself, pregnancy outcomes, and the developing child, and has far-reaching
      repercussions. The major problems that contribute to maternal child morbidity and
      mortality include nutritional deficiencies, lack of safe water, and family
      planning needs. Earlier surveys conducted on maternal nutrition consistently
      showed iron deficiency, goiters, underweight, and inadequate nutrient intake to
      be quite prevalent. On the basis of previous assessments, this project focused on
      educating community health workers on ways to assist families with nutritional
      deficiencies, family planning, and hygiene needs.

PMID- 9601306
TI  - Is science a dangerous Golem?

PMID- 9601307
TI  - Borderline personality disorder: gender stereotypes, stigma, and limited system
      of care.
AB  - In North America, there may be no other psychiatric diagnosis more laden with
      stereotypes and stigma than borderline personality disorder. People who live with
      this label--the majority being female--are often marginalized or denied access to
      mental health services. In this article, the author reviews the theoretical
      underpinnings of the diagnosis, as well as the stigmatizing practices and limited
      services for seriously ill persons with borderline personality disorder
      diagnoses. In light of this review, new directions for mental health practice,
      education, and research are proposed.

PMID- 9601305
TI  - The impact of media attention, family history, politics and maturation on women's
      decisions regarding hormone replacement therapy.
AB  - A purposeful sample of 21 well-educated European American women (42-53 years)
      were interviewed to explore how women make decisions about hormone replacement
      therapy (HRT) for natural menopause. Menopausal status included women who were
      premenopausal (n = 1), perimenopausal (n = 11), menopausal (n = 4), and
      postmenopausal (n = 5). Participants were grouped into 3 categories: taking or in
      favor of taking HRT (n = 6), undecided (n = 10) and stopped taking or opposed to
      taking HRT (n = 5). The impact of media attention was an important influence on
      women's thoughts and decisions-whether in favor, undecided, or opposed-
      particularly in conjunction with risk factors based on family history and what
      other family members were doing. Women in favor of taking HRT were interested in
      short-term symptomatic relief as well as prevention of disease in old age. Women
      who were undecided cited the scientific confusion in the media as contributing to
      their reticence about making a decision. The unprecedented number of magazine,
      book, and newspaper coverage of HRT during the study undoubtably influenced
      women's thoughts and decisions.

PMID- 9601308
TI  - Recommendations for health care professionals to improve compliance and treatment
      outcome among patients with cognitive deficits.
AB  - A significant body of research demonstrates that alcoholics and drug addicts
      presenting for treatment have poor attention and concentration, memory,
      abstraction, and problem-solving skills even after a significant detoxification
      period. Such deficits result in poor understanding of medical and psychological
      treatment recommendations, which is likely to decrease treatment compliance.
      Although psychological test results are frequently available, many health care
      professionals are unfamiliar with the implications of deficits signaled by test
      scores. Even when such testing is available, reports often fail to recommend
      interventions for improving treatment understanding and compliance. The present
      study reviewed the cognitive testing of 206 male veterans admitted to the
      Substance Abuse Treatment Center. Descriptive data, along with implications for
      real-world tasks, are presented. Specific recommendations for providing treatment
      to patients with vocabulary, abstraction, and memory difficulties are made. With
      this information, health care professionals who receive testing reports will be
      better able to relate testing information to patient behavior and to provide
      efficacious treatment.

PMID- 9601309
TI  - Mexican American clients' perceptions of services in an outpatient mental health
      facility in a border city.
AB  - This descriptive-exploratory pilot study analyzed the perceptions of services in
      an outpatient mental health facility located in a border city in southwest Texas
      among Mexican American clientele with chronic mental illness. Face-to-face
      interviews using structured questionnaires were conducted with high functioning
      mentally ill clients. The questionnaire, with both English and Spanish versions,
      consisted of items on sociodemographics, support networks, illness experiences,
      reasons for seeking health services, reactions to being visited in the home
      setting for follow-up care, receiving care from a mental health professional with
      a similar cultural background, satisfactions, problems encountered in the mental
      health delivery system, and suggestions for improving health services. Data from
      56 respondents yielded generally highly favorable and positive ratings of
      services received in the facility. Overall, these baseline data present
      challenges and implications for delivering culturally competent mental health
      care to Mexican American clients with chronic mental illness.

PMID- 9601310
TI  - Feminism: a perspective for the 21st century.
AB  - This article details some of the key elements related to feminism in American
      society. It suggests that the meaning and significance of a feminist perspective
      need to be reexamined for their importance and utility in this dynamic and
      rapidly changing society. A discussion of the meaning of feminism provides a
      framework for the article. Issues related to cultural diversity and the need for
      competent health care delivery for all people are some major themes. The other
      emphasis is related to research and women. Numerous challenges are outlined. A
      feminist perspective is recommended as a conceptual model through which health
      care reform can be enhanced. If feminism were embraced, the health status of
      people would be improved.

PMID- 9601311
TI  - Unexpected outcomes of childhood psychiatric hospitalization.
AB  - This article describes an aspect of a larger study of the experiences, outcomes,
      and consequences of hospitalization during the years that constitute the "for
      profit psychiatric hospital scandal" in Texas. Specifically, this article is
      concerned with patients who were children during 1985-1991. The author presents a
      case study of one such patient, followed by discussion of perceived outcomes as
      well as the long-term professional, economic, and policy sequelae of questionable
      psychiatric hospitalization. Questions are also raised as to the implications of
      applying a purely marketplace orientation to the care of society's most
      vulnerable individuals.

PMID- 9601312
TI  - Emotional distress in women with symptomatic HIV disease.
AB  - This article describes emotional distress in 44 women with Human Immunodeficiency
      Virus (HIV) symptomatic disease. Measures of self-reported symptoms of anxiety
      and depression revealed that emotional distress was prevalent in this group and
      may be sufficiently robust to warrant clinical diagnoses. Limits to functioning
      and disruptions in physical well-being were found to be associated with both
      anxiety and depression. Additionally, level of optimism was inversely related to
      anxiety and depression, and social support was inversely related to anxiety.
      These findings indicate that emotional distress in women with HIV disease is
      associated with, and could be ameliorated by, interventions targeted at
      functional status, social support, and level of optimism.

PMID- 9601313
TI  - Use and morbidity of venous access devices in patients with hemophilia.
AB  - To obtain information on venous access devices (VADs) used for the treatment of
      patients with hemophilia and infections associated with the use of VADs, a
      questionnaire was sent to 153 hemophilia treatment centers in the United States
      and Puerto Rico. Information regarding the treatment of 10,421 patients and 568
      VADs was obtained. Infections were reported with 159 (45%) of 353 internal
      devices and 126 (71%) of 178 external devices. These results indicate that VADs
      used for the treatment of hemophilia are associated with significantly higher
      infection rates than are those used in oncology or mixed patient populations.

PMID- 9601314
TI  - Complications related to intravenous midline catheter usage. A 2-year study.
AB  - The introduction of the Landmark midline catheter (Menlo, Co., CA) brought an
      alternative to central line catheter placement for prolonged intravenous access.
      The study was initiated in 1993 to observe for complications, including
      hypersensitivity-like reactions. The authors hypothesized this i.v. modality
      would decrease the need for central i.v. lines and accompanying complications. At
      the time of catheter insertion, the i.v. team nurses completed a survey form that
      included demographics, underlying disease, and risk factors for infection. The
      catheter tip was cultured at the time of removal. In the second phase of the
      study, the authors focused specifically on hypersensitivity-like reactions.
      During a 2-year period, 248 patients had 334 midline catheters. Patient ages
      ranged from 23 to 98 years (mean age, 65 years). The bacteremia rate was 0.3%;
      the colonization rate was 0.9%. Factors associated with infection/ colonization
      included: length of time in place, chemotherapy, and lack of antibiotic
      administration. In the second phase of the study, during which an additional 170
      catheters were placed in 131 patients, no hypersensitivity-like reactions were
      noted. The midline catheter appears to be a safe method of i.v. fluid
      administration for patients with limited peripheral vein access who need extended
      i.v. therapy.

PMID- 9601315
TI  - Home intravenous antibiotics. The safety factor.
AB  - Home intravenous antibiotic infusion now is a safe and effective alternative to
      patient hospital admittance. With careful guidelines to provide appropriate
      patient selection, education, care planning and device selection, home antibiotic
      infusion can reap impressive results. Patients are more satisfied when they
      receive i.v. antibiotic therapy in the comfort of their homes. Intravenous nurses
      provide the skill and expertise necessary for quality home i.v. antibiotic
      infusions. Home health agencies venturing into the world of home infusion will
      benefit from this article. These guidelines are appropriate for most types of
      home i.v. therapy, not merely antibiotic therapy.

PMID- 9601316
TI  - Thrombotic complications in intravenous access.
AB  - Thrombotic complications of intravenous access represent an entire spectrum of
      disorders. This article addresses the incidence and occurrence of these
      complications. The symptoms of thrombotic disorders of the veins are presented
      along with their natural history. Treatment options are discussed, and the
      applications of preventative measures are covered, relevant to applications in
      i.v. nursing.

PMID- 9601317
TI  - The effects of cumulative grief in the nurse.
AB  - This article describes some of the major causes of stress for nurses and other
      professional care givers who work with the dying, their families, and the
      bereaved. It specifically addresses the stress of cumulative grief in the work
      situation and its effects on the care giver. It also describes some of the
      strategies for the institution and the individual nurse that can be used to
      minimize the effects of stress and cumulative grief and can contribute to
      emotional health in this type of work.

PMID- 9601318
TI  - Downsizing. Use intravenous clinicians to maintain quality venous access care.
AB  - Many authors demonstrate the cost effectiveness of using intravenous teams to
      provide quality venous access care. Despite this evidence, many hospitals are
      dissolving their i.v. teams as a way of cutting costs. This article provides a
      guide for downsizing while maintaining quality i.v. therapy. The article
      chronicles events before and after the disbanding of the i.v. team of the San
      Francisco Veteran's Administration Medical Center. The focus of the article
      demonstrates how creating two advanced practice positions is instrumental to
      maintaining quality i.v. care. Quality is defined as line-associated bacteriemia
      rates and compliance rates to i.v. care standards, remaining unchanged or better
      after the downsizing of the i.v. team. Line-associated bacteriemia rates are
      presented in terms of infections per 1000 line days when possible. Compliance
      percentages are obtained by auditing compliance to site changes, central line
      policy. The data are provided in chart form, and definitely show a sharp decline
      in line-associated bacteremias after the advent of the i.v. clinician role. These
      data provide clear evidence to support the Intravenous Nurses Society position on
      the role of the intravenous nurse specialist. Conclusions emphasize the need for
      i.v. nurse clinicians to provide critical care coverage, ongoing educational
      programs, outcome auditing, and nursing research in vascular access and i.v.
      therapy.

PMID- 9601319
TI  - Hand care. Review in practice.
AB  - Hand care practices have been looked at critically by a number of researchers
      over recent years, and it has become clear that many practitioners do not have
      access to the latest information. This problem is compounded by difficulties in
      self-assessment: the differences between individuals' perceptions of their
      practices and the observations of independent assessors have been noted. Before
      attempting to go forward and take any necessary action, though, the practitioner
      has to know where he or she is at the moment.

PMID- 9601320
TI  - Management of a breast wound with complications.

PMID- 9601322
TI  - Nutrition and pressure damage.

PMID- 9601321
TI  - Ultrasound therapy and wound healing.

PMID- 9601323
TI  - Marjolin's ulcer and chronic burn scarring.
AB  - Marjolin's ulcer is a term used to describe squamous cell carcinomas which
      develop in chronic wounds. These carcinomas may also develop at the site of long
      standing irritation, such as unstable burn scars. Development times for burn scar
      carcinomas of more than 30 years have been noted. This evaluation describes the
      treatment of 10 patients with burn scar carcinomas who have been treated using
      wide excision and closure of the defect with skin grafts or flaps, plus regional
      lymph node dissection if required. Results indicate a mean carcinoma development
      time of 26 years. Local recurrence occurred in only one patient.

PMID- 9601324
TI  - Construction and calibration of a low-cost bandage pressure monitor.
AB  - This study describes the construction and calibration of a three-channel bandage
      pressure monitor and evaluates its in-service use. The monitor was constructed
      from a range of commercially available, relatively inexpensive components
      consisting of a pressure sensor, piezoresistive transducer, differential
      amplifier and liquid crystal display. The pressure sensors show a good ratio of
      thickness to surface area (< 10%) and are sufficiently robust and flexible to
      conform to most anatomical profiles. The transducers are internally calibrated
      and temperature-compensated to provide an accurate and stable measurement of
      gauge pressure relative to atmospheric pressure. During laboratory assessment and
      in-service use, the system has proved to be reliable, accurate (typically < +/-
      0.5 mmHg) and reproducible over repeated calibration.

PMID- 9601325
TI  - Using a bandage pressure monitor as an aid in improving bandaging skills.
AB  - This prospective study used a bandage pressure monitor to assess the bandaging
      skills of 16 nurses caring for patients with venous leg ulcers. Baseline
      measurements showed that only 50% of the nurses demonstrated bandaging skills
      that were adequate to good. However, by the end of the feedback/post-training
      session, 81% of those examined had reached this standard and this figure rose to
      86% on recall. These data seem to support the view that the use of a pressure
      monitor is a useful adjunct in the teaching of bandaging skills.

PMID- 9601326
TI  - Lower-limb amputation: wound care and rehabilitation.

PMID- 9601327
TI  - The investigation and assessment of venous disease.

PMID- 9601328
TI  - The evidence in support of compression bandaging.

PMID- 9601329
TI  - Innovations in leg ulcer care.

PMID- 9601330
TI  - The use of pressure support equipment in nursing homes.

PMID- 9601331
TI  - [Hygienic measures in infectious hepatitis and HIV infection--a summary].

PMID- 9601332
TI  - [Incontinence--what is it?].

PMID- 9601333
TI  - [Urinary incontinence in the elderly].

PMID- 9601334
TI  - [How many incontinent patients are there today and how many will there be
      tomorrow?].

PMID- 9601335
TI  - [Care of patients with stomas].

PMID- 9601337
TI  - [Role of the professional nurse in home therapy].

PMID- 9601336
TI  - [Patient safety with lower costs. Precise blood sugar determination: an important
      element in the diagnosis and therapy of diabetes].

PMID- 9601338
TI  - [Sandimmun Optoral now approved in Germany. Treatment of rheumatoid arthritis].

PMID- 9601339
TI  - [Home care makes it possible. Well nourished and fit onto old age].

PMID- 9601340
TI  - [Glaxo reduces the price for Retrovir in developing countries. Program to stem
      further spread of HIV].

PMID- 9601341
TI  - [Cutinova bandages tested: other bandages, other costs].

PMID- 9601342
TI  - [Henkel is doing without animal experiments for mucosal antiseptic. Skinsept
      mucosa: a new in vitro procedure proves excellent tolerance].

PMID- 9601343
TI  - [Psychologists who created a school (II). Carl Gustav Jung (1875-1961)].

PMID- 9601345
TI  - Acyanotic cardiac lesions with normal pulmonary blood flow.
AB  - This article, the second in a series discussing acyanotic cardiac defects,
      examines acyanotic cardiac defects with normal pulmonary blood flow: pulmonary
      stenosis, peripheral pulmonary stenosis, coarctation of the aorta, and valvular
      aortic stenosis. A similar defect, interrupted aortic arch, is also discussed.
      The hemodynamics, clinical presentation, differential diagnosis, surgical repair,
      and medical management of each defect are presented. Parental teaching needs are
      identified and discussed.

PMID- 9601346
TI  - Congenital infantile fibrosarcoma: a case study.
AB  - Congenital infantile fibrosarcoma (CIFS) is a rare soft-tissue malignancy most
      commonly involving the extremities. Metastases are rare; however, local
      recurrence is common. Because the tumor is so rare and clinical experience is
      lacking, both diagnosis and treatment are difficult. The complex planning and
      implementation of neonatal and oncologic care require ongoing collaboration
      between both nursing specialties. This case study discusses the pathophysiology,
      diagnosis, and management of an infant with CIFS, with emphasis on the nursing
      care of the patient and family.

PMID- 9601347
TI  - A comparison of temperature in VLBW infants swaddled versus unswaddled in a
      double-walled incubator in skin control mode.
AB  - PURPOSE: To determine differences in temperature for very low birth weight (VLBW)
      infants when swaddled and unswaddled in heated, double-walled incubators. DESIGN:
      A crossover design was used with infants receiving both the swaddled and
      unswaddled conditions. SAMPLE: 15 very low birth weight infants (< 1,500 gms)
      with postconceptional ages of 29.1 +/- 1.5 weeks. MAIN OUTCOME VARIABLE: Infant
      temperature in swaddled and unswaddled conditions. RESULTS: Abdominal
      temperatures during swaddling were 0.2 degree C higher than the unswaddled
      condition. In the swaddled condition, infants required a lower incubator
      temperature (mean = 26.9 +/- 0.4) than when unswaddled (mean = 29.8 +/- 0.5).

PMID- 9601348
TI  - Initiation and maintenance of a hospital-based parent group for parents of
      premature infants: key factors for success.
AB  - The impact of a premature birth can be very traumatic for parents. They are
      usually not prepared for this event, and their sense of grief and loss is so
      intense that they often have difficulty coping with the situation. A parent group
      can help parents adapt to the crisis of prematurity by providing information and
      family support. This article describes the development of a parent group at a
      regional perinatal center in Ontario and identifies key factors for its
      successful initiation and maintenance.

PMID- 9601349
TI  - HCFA support may affect all APNs.

PMID- 9601351
TI  - The use of erythropoietin in treatment of anemia of prematurity.

PMID- 9601352
TI  - Newborn genetic screening.

PMID- 9601353
TI  - RSV-IG (respigam).

PMID- 9601354
TI  - Tearing and embolization of percutaneous central venous catheters.

PMID- 9601355
TI  - Swimming with the fishes.

PMID- 9601356
TI  - CAPD and a journey to Israel.

PMID- 9601357
TI  - 1998 camps for patients with ESRD.

PMID- 9601358
TI  - CVVH: a kinder, gentler approach to acute renal failure interview by Mark E
      Neumann.

PMID- 9601359
TI  - Flying high on daily hemodialysis.

PMID- 9601361
TI  - Negotiations and socialized medicine.

PMID- 9601360
TI  - Empowering patients.

PMID- 9601362
TI  - Dialyzer reuse in Europe: current status and perspectives.

PMID- 9601363
TI  - NRAA responds to proposed $1 cut in EPO reimbursement.

PMID- 9601364
TI  - Manpower issues outside the U.S. Canada looks at its supply of nephrologists.

PMID- 9601365
TI  - Balancing the budget: what does it mean for the renal community?

PMID- 9601366
TI  - RPA: the year in review.

PMID- 9601367
TI  - Roots & uprisings of the RPA.

PMID- 9601369
TI  - Helping patients, renal staff gain access to information.

PMID- 9601368
TI  - Nephrology in the future.

PMID- 9601370
TI  - Number of centers reporting VRE cases in 1996 doubled. CDC survey also shows
      tuberculosis reappearing.

PMID- 9601371
TI  - NKF embraces broad concept of rehabilitation with RISE program.

PMID- 9601372
TI  - Cost savings, nutritional status, improved solutions help secure the future role
      of PD.

PMID- 9601373
TI  - Myths & facts ... about poison ivy.

PMID- 9601374
TI  - When a child needs peripheral i.v. therapy.

PMID- 9601375
TI  - Safeguarding cardiac guide wires.

PMID- 9601376
TI  - Understanding sexually transmitted diseases, Part II.

PMID- 9601377
TI  - Actionstat. Aspirin overdose.

PMID- 9601378
TI  - Answers to your questions about domestic violence. "Why don't you just leave
      him?".

PMID- 9601379
TI  - Chemotherapy complications.

PMID- 9601381
TI  - Respiratory assessment revisited.

PMID- 9601380
TI  - In a crisis, small gestures can make a big difference. 3 warm blankets.

PMID- 9601382
TI  - Getting comfortable with alternative & complementary therapies.

PMID- 9601383
TI  - Going with the flow. How to prevent feeding tubes from clogging.

PMID- 9601384
TI  - Setting your boundaries.

PMID- 9601385
TI  - Code blue. Defibrillate.

PMID- 9601386
TI  - Liberate yourself from a triangle of conflict.

PMID- 9601387
TI  - Keeping your balance.

PMID- 9601388
TI  - Correcting charting errors.

PMID- 9601389
TI  - Preventing transient increases in intracranial pressure.

PMID- 9601390
TI  - Misoprostol and diarrhea.

PMID- 9601391
TI  - Better than medicine.

PMID- 9601392
TI  - In the eye of the beholder.

PMID- 9601393
TI  - Listen: a life may depend on it.

PMID- 9601394
TI  - Athletic physeal injury in children and adolescents.
AB  - Physeal injuries occur in 15% of children with fractures, and 10% of all physeal
      injuries are sport related. Soccer, alpine skiing, gymnastics, weight lifting and
      baseball are sports commonly associated with physeal injury. Swelling, hyperemia,
      and deformity in the physeal area are the classical signs of physeal injury. Pain
      may be less intense than with other fractures. Treatment usually includes
      immobilization. Growth disturbance depends on extent of the injury and the amount
      of remaining growth potential. Prevention should focus on sport participation
      within the parameters of ability, maturation, and use of proper equipment.

PMID- 9601395
TI  - Multiple sclerosis update.
AB  - Multiple sclerosis (MS) is the most common central nervous system disease among
      young adults and the third leading cause of disability in the United States. It
      is estimated that 400,000 Americans have this disorder of the brain and spinal
      cord, which causes disruption in the smooth flow of electrical messages from the
      brain to nerves throughout the body. The clinical manifestations vary more in MS
      than any other neurologic disease. Because of the complexity of MS, a
      collaborative approach to care of these clients and their family is ideal. This
      article provides an update on the diagnosis, pharmacologic management, and
      collaborative care for patients and families.

PMID- 9601396
TI  - Transitioning yourself into the new health care business.
AB  - This article discusses the impact of the evolving health care industry on the
      individual staff nurse. It identifies future trends that affect nursing's role
      within the acute care setting, as well as the skills and characteristics of the
      successful nurse of the future. Ideas and suggestions for success in this new
      environment are presented in a nonintimidating way. Methods to obtain information
      on future nursing roles are discussed, and implications for current nursing roles
      are presented in an informal and easily understood way. Ideas on ways for staff
      nurses to assess their career options, as well as plan for any potential
      downsizing in their existing facilities, are also discussed. The idea that each
      nurse must take an active role in their own career development and not wait for
      someone else to do it or assume they will be taken care of runs throughout the
      article.

PMID- 9601397
TI  - Violence against women: the role of orthopaedic nurses in the identification,
      assessment, treatment, and care for the abused woman.
AB  - Violence against women is a significant public health problem that affects women
      of all age groups across the life span. This article presents a review of
      domestic violence against women and outlines the role of orthopaedic nurses in
      the identification, assessment, treatment, and care of women patients with
      injuries or medical problems sustained as a result of domestic abuse from an
      intimate other. Key interventions for the treatment and care of abused women
      include (a) acknowledging the abuse, (b) discussing safety planning, (c)
      discussing the pattern of abuse, (d) anticipating and respecting the partial
      denial, (e) reassuring the woman that abuse is not her fault; (f) informing the
      woman that no one deserves to be abused, (g) telling the woman gently that help
      is available, (h) reminding the woman that domestic violence is a crime, (i)
      referring to community resources, and (j) allowing the woman to decide which
      support services and options are safe for her situation.

PMID- 9601398
TI  - Fat embolism syndrome: a complication of orthopaedic trauma.
AB  - Fat embolism syndrome is a potentially serious, life-threatening complication of
      long bone fractures, blunt trauma, and intramedullary manipulation. The
      orthopaedic nurse needs to have an understanding of fat embolism syndrome (FES),
      its pathophysiology, the varied aspects of its clinical presentation, and an
      understanding of treatment protocols and rationale.

PMID- 9601399
TI  - The inadvertent breach of confidentiality.
AB  - Patients believe that personal information that they share with their health care
      providers will be kept strictly confidential. Safeguarding a confidence has been
      and continues to be an expected professional behavior. Yet, a common ethical
      problem that nurses face in their everyday practice is the inadvertent disclosure
      of private information about particular patients to individuals who have no need
      for this information. This article discusses the inadvertent breach of
      confidentiality and its related ethical concepts: privacy, respect for persons,
      trust and fidelity, and the potential for harm or injury. Recommendations are
      provided to enable nurses to avoid and manage situations that involve an
      inadvertent breach of confidentiality.

PMID- 9601400
TI  - Orthopaedic nursing research priorities: a replication and extension.
AB  - PURPOSE: This study identified current orthopaedic nursing research priorities
      that should be investigated to advance the practice of orthopaedic nursing. The
      study was accomplished by the National Association of Orthopaedic Nurses' (NAON)
      Research Committee via a national survey of selected NAON members. DESIGN: A
      descriptive design was used to determine research priorities. SAMPLE: The sample
      consisted of a random sample of 133 NAON members. The sample was stratified for
      either graduate degrees (> or = master's), other than a graduate degree (< or =
      bachelor's) (to insure representation from "frontline" practicing nurses), and
      registrants in the NAON Researcher Database and recipients of NAON Foundation or
      American Academy of Orthopaedic Surgeons (AAOS)/NAON grants. METHOD: A three
      round Delphi survey technique was used to build consensus by systematically
      generating, synthesizing, and analyzing opinions of a group of experts while
      maintaining confidentiality of the individuals. MAIN RESEARCH CLASSIFICATIONS:
      Nursing research priorities, Delphi method, Orthopaedic nursing. FINDINGS: The
      nine target research questions for orthopaedic nursing identified as high
      priority were grouped into the following categories: patient acuity, care
      delivery models, staffing issues, patient complications, pain management (in the
      elderly and those with altered mental status), and patient mobility. These
      research priority items are intended to direct the orthopaedic nurse researcher
      to study specific questions within these categories. CONCLUSION: Results reflect
      the dramatic changes occurring in orthopaedic nursing practice. Research
      priorities reveal the need for more research on pain and patient complications
      (e.g., deep vein thrombosis (DVT)) despite a preponderance of existing, published
      research on these topics. IMPLICATIONS FOR NURSING RESEARCH: This study
      identified target research questions for orthopaedic nursing. These questions may
      be used by orthopaedic nurses to develop nursing research proposals as well as
      collaborative research endeavors with other members of the orthopaedic health
      care team. An ongoing and wider dissemination of results of existing research to
      the NAON membership needs to be implemented.

PMID- 9601401
TI  - Open book (AP compression) pelvis fracture.
AB  - A simple pelvic fracture classification is presented based on the metaphor of a
      pelvis as a book. Resuscitative fluid and blood requirements can be estimated by
      knowledge of the pelvic fracture pattern. Open book (AP compression) pelvis
      fractures generally have the largest amounts of blood loss.

PMID- 9601403
TI  - Learning about bone mass measurement.

PMID- 9601402
TI  - Osteoporosis independent study.

PMID- 9601404
TI  - Introducing... Sandy Cahill.

PMID- 9601405
TI  - Case management: unraveling the confusion.
AB  - I'm going to close with some of my ideas about the characteristics that case
      managers exhibit. I have a great deal of professional respect for case managers.
      I think that you are a tenacious lot. One of the major things that case managers
      do is help create new alternatives to problems. You open doors; no ... you first
      build the door and then you open it. You're creative, persistent, and
      resourceful. You are sometimes asked to solve all of an organization's problems.
      I think that is a tremendous burden, and that you can get confused because of
      that role conflict and confusion. What model is best for my organization? Within
      that is my patient population. What is it that they need? What are the current
      issues that you are seeing? How is my case management role different from other
      roles? How large a scope of practice can I handle and be reasonably successful
      with the patients with whom I'm dealing? How many different kinds of approaches
      and models are needed within my organization? Look toward the future; think about
      the future in terms of your crystal balls. What trends do you see building in
      either the demographics or the health and social environments that are going to
      influence health care in the future? What effect will the aging of our population
      have on you and your case management practice? What issues are going to be
      related to those trends? How many more people do we have living in fragmented
      families? What's going to happens in terms of resources available for patients?
      How can case management influence those changes? I don't think we're going to see
      the pace of change in the health care industry slow down. We will continue to
      have health care organizations address social issues in addition to
      pathophysiologic ones. No matter what the role and how it evolves, case
      management will always be at the junction of change in health care. This will be
      difficult at times to deal with. It will also be a source of satisfaction for
      those in the role because of the tremendously positive effect case managers have
      on the lives of patients and their families.

PMID- 9601406
TI  - Outcomes management: who, what, where, why, how.

PMID- 9601407
TI  - Work injuries: circumstances for orthopaedic case management.

PMID- 9601408
TI  - Reducing lengths of stays in the total joint replacement population.

PMID- 9601409
TI  - Parish nursing: a community-based outreach program of care.

PMID- 9601410
TI  - Total joint replacement preadmission programs.
AB  - Patients begin to formulate their expectations of the postoperative
      hospitalization during the preadmission program. The challenge is to better
      understand the factors patients consider when formulating judgments about the
      quality of preadmission education. For example, it may be that perceptions of the
      preadmission program are influenced by what patients believe about their
      postoperative pain and functional abilities. Specific attention needs to be given
      both preoperatively and postoperatively to instructing patients on realistic
      expectations for recovery. One other method of measuring patient outcomes is with
      the Health Status Profile (SF-36) (Response Healthcare Information Management,
      1995). The SF-36 approach emphasizes the outcome of medical care as the patient
      sees it, in addition to a clinical evaluation of successful health care. This
      form is currently initiated in the physician's office and returned for scanning
      at the preadmission class. The patient then completes another SF-36 at 6 months
      and every year thereafter to compare measurable outcomes. Patients intending to
      have elective total joint replacements experience anxiety and require much
      support and education. An effective preadmission program is a major investment in
      a patient's recovery, as well as a unique marketing tool to customers.
      Preadmission programs can be viewed as an opportunity to enhance customer
      satisfaction. Preadmission clinics are an excellent means for nurses to improve
      the quality of patient care through patient education. the overall goal of
      preadmission testing programs is to ensure patient preparedness while increasing
      quality health care and overall customer satisfaction. To enhance program
      effectiveness, health care providers must lead collaborative efforts to improve
      the efficiency of systems.

PMID- 9601411
TI  - Patient population management: taking the leap from variance analysis to outcomes
      measurement.
AB  - Case managers today at BCHS have a somewhat different role than at the onset of
      the Collaborative Practice Model. They are seen throughout the organization as:
      Leaders/participants on cross-functional teams. Systems change agents.
      Integrating/merging with quality services and utilization management. Outcomes
      managers. One of the major cross-functional teams is in the process of designing
      a Care Coordinator role. These individuals will, as one of their functions,
      assume responsibility for daily patient care management activities. A variance
      tracking program has come into the Utilization Management (UM) department as part
      of a software package purchased to automate UM work activities. This variance
      program could potentially be used by the new care coordinators as the role
      develops. The case managers are beginning to use a Decision Support software,
      (Transition Systems Inc.) in the collection of data that is based on a cost
      accounting system and linked to clinical events. Other clinical outcomes data
      bases are now being used by the case manager to help with the collection and
      measurement of outcomes information. Hoshin planning will continue to be a
      framework for defining and setting the targets for clinical and financial
      improvements throughout the organization. Case managers will continue to be
      involved in many of these system-wide initiatives. In the words of Galileo, 1579,
      "You need to count what's countable, measure what's measurable, and what's not
      measurable, make measurable."

PMID- 9601412
TI  - Being competitive in a managed care marketplace.

PMID- 9601413
TI  - Care coordination for children with special health care needs.

PMID- 9601414
TI  - A glimpse over the horizon: choosing our future.
AB  - There are three things this presentation sought to accomplish. First, it's not
      the health care system you grew up with any longer. Even if you wanted to keep
      it, it's already gone. And we need to join hands and mourn the loss. We nurses
      don't mourn well--we just mourn long. So we need to join hands and mourn the loss
      and cry deeply for 5 to 15 minutes. Or else we need to laugh until it's out. Then
      we can get on with the work of constructing our future. Second, I wanted to give
      you a picture of the different context in which we live ... from the industrial
      age to the new age ... so you have an idea of the different elements that make up
      the age into which we're going that no longer looks like the age that we're
      leaving. Third, I wanted you know what was in the winds: subscriber-based
      management of life health care, fixing the price for that health care in advance
      of providing it, and inexorably and painfully building that continuum of
      services, that will necessarily have to be in place in order to provide the
      service that we will need to provide in order to sustain health care in the
      country. That's the road that we are on, and it's a noisy road, but it's also an
      exciting road. There are not going to be major successes. There is going to be a
      whole series of small successes, and you're going to have to celebrate your
      successes as you go. We don't celebrate very well either. We celebrate small
      successes. You have to celebrate the journey. Remember that in the systems
      definition of success, success is as sufficient appropriate aggregation of
      sufficient error. Only when you've aggregated sufficient error do you have the
      measure of success. Honor error, honor the pain, take moments to celebrate the
      journey for whatever reason you have so that the journey has meaning. You are
      going to be a leader and on your shoulders is going to be the expectation of
      providing leadership. Something in the course of our time together or your time
      here at the conference, resonated with your own consciousness, your own thinking,
      your own journey, your own experience, and your own leadership. Margaret Wheatly
      said in her book, Leadership in the New Science, talking about quantum mechanics
      applied to leadership: "The change is like a ripple; it doesn't matter where you
      make change, it doesn't matter how large the ripple, it doesn't matter how
      isolated you may feel, if you make the change it creates a ripple that ultimately
      changes everything".

PMID- 9601415
TI  - [Nursing in a dispensary in the bush].

PMID- 9601416
TI  - [When art rescues health].

PMID- 9601417
TI  - [Surgical rehabilitation of the upper extremities in tetraplegic patients].

PMID- 9601418
TI  - [Cataract excision in 3 hours. My eye! and yet...].

PMID- 9601419
TI  - [AIDS, a change in values].

PMID- 9601420
TI  - [AIDS in 1998: the most important work still has to be done].

PMID- 9601422
TI  - [A painful revival].

PMID- 9601421
TI  - [The antiretroviral agents].

PMID- 9601423
TI  - [Diary of infection].

PMID- 9601424
TI  - [From mourning over life to mourning over death].

PMID- 9601425
TI  - [AIDS: everybodies business].

PMID- 9601426
TI  - [Prevention a la carte].

PMID- 9601427
TI  - [Should the nursing profession be organized into associations?].

PMID- 9601428
TI  - [At the end of the line...].

PMID- 9601429
TI  - Ready, set, transport!

PMID- 9601430
TI  - Assess for HIV, too.

PMID- 9601431
TI  - Meeting special learning needs.

PMID- 9601432
TI  - Save those old journals.

PMID- 9601433
TI  - Low molecular weight heparin.

PMID- 9601434
TI  - Left ventricular assist devices.

PMID- 9601435
TI  - Pediatric liquid ventilation.

PMID- 9601436
TI  - Can these compounds curb arthritis?

PMID- 9601437
TI  - Getting informed consent.

PMID- 9601438
TI  - What's causing this arrhythmia?

PMID- 9601439
TI  - Equal care--could it be a reality?

PMID- 9601440
TI  - A concept analysis of energy. Its meaning in the lives of three individuals with
      chronic illness.
AB  - Energy is an essential concept in nursing which seems to be a key concept in the
      daily life of three individuals with chronic illness. Much has been done within
      the natural sciences to investigate and explain the concept, but studies on the
      meaning of energy and how it is experienced are difficult to find. A review of
      the existing literature reflects that energy has been an important term for
      nursing theorists, both in empirical studies and in nursing theories. In this
      study the principles of the hybrid model developed by Schwartz-Barcot & Kim of
      concept development were used to examine: (a) how the concept has been outlined
      in the literature within different disciplines, (b) how energy is experienced in
      the daily lives of three individuals with chronic illness, and finally, (c) the
      existing literature compared and contrasted with the empirical findings. The
      experience of having energy was very important for all three individuals. Energy
      was a familiar term which each individual linked most directly with his or her
      feeling states and the ability to perform daily activities. It demanded attention
      every day. Energy was defined as the individual's potential to perform physical
      and mental activity. The study indicates that this concept has potential for
      theory development and for clinical practice.

PMID- 9601441
TI  - The use of and need for patient classification systems in Swedish neonatal care.
AB  - Patient Classification Systems (PCSs) comprise a large group of instruments which
      describe the condition of a patient regarding severity of disease, severity of
      illness, risk factors, intensity of nursing care, costs, and so on. They are
      advocated as an essential ingredient in outcome assessment, but the application
      of PCSs extends beyond research activities. The aim of this study was to
      investigate the use of and need for PCSs in Swedish neonatal care units as well
      as the need for evaluation and improvement of the systems already in use. A
      survey of 44 units revealed a low level of experience in the use of these
      systems. Among the 20 units using PCSs, only a few applied standard systems and
      11 units pointed out the need for improving these systems. In addition, a second
      study, based on participant observation and interviews, indicated some potential
      applications of PCS in a specific unit, such as standard criteria for referring
      mothers and newborns, staff allocation, staff education and training, standard
      criteria for parent information, and prognostic systems for medical decision
      support. Evaluation and adaptation of the existing systems, which are generally
      developed outside the country, are necessary before they can become a tool for
      quality assurance, if a national programme for quality of neonatal care is to be
      established in Sweden.

PMID- 9601442
TI  - Assessment Instrument for Problem-focused Coping. Reliability test of APC. Part
      1.
AB  - A new self-report instrument, the Assessment Instrument of Problem-focused Coping
      (APC) developed from qualitative interviews, is described. This instrument
      provides knowledge of the patients' own competence in coping with activities of
      daily living (ADL), the patients' own assessment of what they experience as
      problems, and the extent to which they are satisfied with their ADL. The purpose
      of the study was to test the reliability of the instrument with regard to intra
      rater reliability and internal consistency. The study group comprised 40 patients
      with muscular weakness and other symptoms relating to the postpolio syndrome. The
      result showed an acceptable internal consistency (alpha 0.70), which confirms the
      construct validity of the instrument. The test-retest showed that the stability
      over a period of time varied from low to high for a total of 28 items. At the
      same time, it is evident that the instrument does not achieve the aim of being a
      good evaluation instrument, because the stability over a period of time was
      unsatisfactory. The test-retest should be repeated with a larger test group in
      future research projects.

PMID- 9601443
TI  - Psychological patterns in patients with coronary heart disease, chronic pain and
      respiratory disorder.
AB  - Patients with coronary heart disease (CHD), chronic pain and respiratory disorder
      were investigated for different patterns of psychological factors. Several
      psychological factors were measured: depression (using Beck's 'BDI'), anxiety
      (using Spielberger's 'STAI'), anger (Spielberger's 'AX'), and cynicism
      (Greenglass & Julkunen's 'CD'). The special psychological pattern in patients
      with CHD was characterized by an increase in suppressed anger, overall
      experienced anger, and cynicism. Patients with chronic pain did not show any
      comparable pattern of elevated psychological factors. The pattern in patients
      with respiratory disorder was characterized by increased cynicism and, in women,
      also clinical depression.

PMID- 9601444
TI  - The view of caring among patients and personnel.
AB  - All patients in hospital care and primary health care in the country of
      Vasterbotten, Sweden (n = 5158) were asked to express their level of satisfaction
      with the quality of care. The study was carried out on one specific day. All
      personnel on duty that day (n = 2824) were also included and asked to give their
      interpretations of their patients' experiences. A questionnaire containing
      positive and negative statements concerning both the relationship and the task
      aspects of care was used. The results showed that the youngest and oldest
      patients expressed the highest degree of satisfaction, while young and middle
      aged patients expressed a more restrained view. The least satisfactory aspects
      concerned the opportunities to express criticism and the possibilities of
      receiving information about access to help outside the health care organization.
      The personnel's responses agreed with those of the patients, but fewer personnel
      thought that their patients were satisfied than was in fact the case.

PMID- 9601445
TI  - Social activities in elderly patients with severe mental illness. Lessons from a
      mental hospital in Sweden.
AB  - Mental hospitals offer their patients many different kinds of social
      activities/facilities. One-hundred-and-twenty-seven patients in the long-term
      care unit at a mental hospital were included in the study. They were divided into
      three subgroups on the basis of diagnosis: dementia disorder (n = 65), chronic
      psychotic disorder (n = 38), and chronic non-psychotic disorder (n = 24). An
      inventory was made of all possible activities/facilities offered to the patients
      by the mental hospital, with the objective of ascertaining whether participation
      in social activities/facilities discriminated between the three diagnostic
      groups. Sixteen activities/facilities were obtained from an inventory by nurses.
      Stepwise discriminant analysis identified length of stay in hospital, age and the
      social activities/facilities that separated the three diagnostic groups. The
      discriminant function analysis showed that participation in social activities,
      together with length of stay and age, discriminated very well between the
      demented and the chronic psychotic groups. The discriminant analysis also
      indicated that patients with chronic psychotic. disorder were distinguishable by
      their frequent participation in social activities, long stay in hospital, and low
      age. The results obtained can be used when the social activities/facilities in a
      community care setting are being planned for the various diagnostic groups.

PMID- 9601446
TI  - Physical restraints in geriatric care. Knowledge, attitudes and use.
AB  - The aim of the present study was to investigate the use of physical restraints in
      institutional elder care and staff knowledge about and attitudes toward the use
      of these restraints. Poor knowledge and negative attitudes toward the use of
      restraints were found among staff. Significant differences between various staff
      categories were found concerning knowledge about the use of restraints; nurse
      aids had the lowest and physicians the highest scores on the knowledge test.
      Nurse aids demonstrated the least negative attitudes (were most prone to use
      restraints) and physicians the most negative. Furthermore, there was a
      significant relation between attitudes and knowledge, i.e. staff with poor
      knowledge also demonstrated the least negative attitudes toward the use of
      restraints. Despite these negative attitudes among staff, we found a large
      proportion of restrained patients in the institutions investigated. Twenty-nine
      percent of the patients at the investigated clinics were physically restrained.
      The most common reason given was that restraints were used to prevent falls. No
      documentation of the observed use of restraints was found in any of the
      restrained patients' hospital records.

PMID- 9601447
TI  - Review of Finnish nursing research from 1958 to 1995.
AB  - This article provides a review of Finnish nursing research between 1958 and 1995.
      It is based on an analysis of the articles published in the Finnish Yearbook of
      Nursing from 1958-1988, in Nursing Science (Hoitotiede) from 1989-1995 as well as
      all licentiate and doctoral theses in nursing. The overview describes the
      content, sources of information and level of analysis in the works concerned.

PMID- 9601448
TI  - [Decontamination. Treatment of instruments before disinfection or sterilization].

PMID- 9601449
TI  - [Methods of sterilization].

PMID- 9601450
TI  - [Sterilization in the operating room. How to create confidence?].

PMID- 9601451
TI  - [Quality assurance of central sterilization. Safety in the hospital].

PMID- 9601452
TI  - [Circular DGS/VS2-DH/EM1/E01/97-627 from 20 October 1997 relating to
      sterilization of medical instruments in health facilities].

PMID- 9601453
TI  - [Resuscitation. The nursing personnel facing an emergency. What approach? What
      are the solutions?].

PMID- 9601454
TI  - [A method of evaluation for health services].

PMID- 9601455
TI  - [Priorities in accreditation according to health professionals].

PMID- 9601456
TI  - [The nurse and her grief. Strategies for intervention].

PMID- 9601457
TI  - [Carrying out medical prescriptions. Difficulties of a daily practice].

PMID- 9601458
TI  - [Absorption, resorption].

PMID- 9601459
TI  - [For a general mobilization of the nursing profession].

PMID- 9601460
TI  - [Suicide and unemployment].

PMID- 9601461
TI  - [At last a solution to the status of psychiatric nurses].

PMID- 9601462
TI  - [Paget's disease of bone].

PMID- 9601463
TI  - [Hygiene is health but it is not necessarily bathing].

PMID- 9601464
TI  - [Washing, a history of water, mind and soul].

PMID- 9601465
TI  - [Washing in psychiatry. From a banal act to individual care].

PMID- 9601466
TI  - [Washing and autonomy].

PMID- 9601467
TI  - [Where there is hygiene there is pleasure].

PMID- 9601468
TI  - [The last bath].

PMID- 9601469
TI  - [Schizophrenia. Incapacity of attending to one's own hygiene. Utilization of a
      nursing diagnosis].

PMID- 9601470
TI  - [Psychologic suffering, social context and exclusion].

PMID- 9601471
TI  - [Fred helps Eric].

PMID- 9601472
TI  - [AIDS: anthropological perspectives].

PMID- 9601473
TI  - [Photodynamic diagnosis of gastrointestinal precancerous lesions after
      sensitization with 5-aminolevulinic acid. A pilot study].
AB  - BASIC PROBLEM AND OBJECTIVE: Endoscopic diagnosis of gastrointestinal
      precancerous and cancerous lesions is difficult, often even impossible. This
      study was undertaken to find out whether premalignant or suspected malignant
      tumors can be diagnosed by preceding sensitization with 5-aminolaevulinic acid
      (ALA), which in tumors is transformed in increased amounts into photosensitizing
      protoporphyrin IX, the latter being recognized by its characteristic red
      fluorescence on exposure to blue light. PATIENTS AND METHODS: 20 patients with
      known mild or moderately severe dysplasias (Barrett's esophagus, n = 8;
      colorectal adenoma, n = 3; ulcerative colitis n = 2, and gastric polyps or
      mucosal changes suspicious of malignancy, n = 5. Two patients with squamous-cell
      carcinoma, who after radio- and chemotherapy were endoscopically free of tumor,
      were sensitized with different concentrations of ALA (orally: 5-30 mg/kg; or
      locally: 3 g in 100 ml 0.9% NaCl). Photodynamic diagnosis (PDD) took place 4-8 h
      after oral and ca. 1-2 h after local sensitization with blue light (D-light,
      Storz, Tuttlingen, Germany). RESULTS: Definite red fluorescence with
      demonstration of dysplasia was found in three of four patients with Barrett's
      esophagus. Biopies from nonfluorescent areas were free of dysplasia. Two gastric
      adenomas (10 mg/kg ALA with high-grade dysplasia were definitively endoscopically
      by their red fluorescence. In one patient mild dysplasia was found in a non
      fluorescent area after radio- and chemotherapy of an esophageal carcinoma.
      Dysplasias were also seen in the rectal biopsy after local applications.
      CONCLUSIONS: PDD makes it possible for the first time to visualize precancerous
      lesions of the gastrointestinal tract after preceding ALA sensitization. PDD is a
      highly promising method for monitoring patients with gastrointestinal disease and
      an increased risk of cancer, and for clarifying the diagnosis of mucosal changes
      suspicious of malignancy.

PMID- 9601474
TI  - [Secondary obstructive sleep apnea syndrome in a patient with tracheal stenosis
      and bilateral recurrent paresis. Successful treatment with nasal continuous
      positive airway pressure therapy].
AB  - HISTORY AND ADMISSION FINDINGS: A 67-year-old woman complained of marked daytime
      sleepiness, as well as loud snoring and apnoeas during sleep. She was known to
      have had 3 thyroidectomies for goitre 41, 23 and 12 years ago, with known
      tracheal stenosis and recurrent nerve palsy for 11 years. Physical examination
      revealed marked stridor, hoarse voice and slightly enlarged and palpable
      recurrent right thyroid. INVESTIGATIONS: Polysomnography demonstrated a clearly
      elevated obstructive sleep apnoea activity (apnoea index: 34/h, apnoea-hypopnea
      index: 40/h, desaturation index: 31/h, minimal saturation: 63%). Selective
      tracheal imaging showed subglottic tracheal stenosis with an inspiratory luminal
      diameter of 4 mm and an expiratory luminal diameter of 8 mm. Lung function
      analysis revealed marked flattening of the flow-volume curve as sign of a
      functionally effective tracheal stenosis. These findings indicated a secondary
      obstructive sleep apnoea (OSA) due to tracheal stenosis and bilateral recurrent
      nerve palsy. The patient declined further studies, such as bronchoscopy.
      TREATMENT AND COURSE: As the patient did not want any surgical treatment, nasal
      continuous positive airway pressure therapy (CPAP) was instituted as a trial. No
      apnoea occurred at a pressure of 12 mm H2O and this was well tolerated. She has
      now continued CPAP at home for 12 months and her vigilance was markedly improved.
      CONCLUSIONS: Tracheal stenosis or recurrent nerve palsy is a rare cause of OSA
      which can be effectively treated by nasal CPAP.

PMID- 9601475
TI  - [Acne comedonica following radiation therapy].
AB  - HISTORY AND CLINICAL FINDINGS: A 50-year-old female patient underwent extirpation
      of a moderately differentiated, partially tubular ductal carcinoma of the left
      mamma and dissection of the left axilla followed by postoperative radiation
      therapy (total dose 58/48 gy). 2 weeks after the radiation therapy was stopped,
      treatment with goserelin subcutaneously was started. 6 weeks later numerous open
      and closed comedons appeared which were sharply confined to the radiation areas
      of left mamma and sternum. DIAGNOSIS, TREATMENT AND COURSE: Because of the
      clinical diagnosis of acne comedonica following radiation therapy a local
      treatment with benzoyl-peroxide gel 5% and erythromycin cream 2% was performed,
      which led to improvement of the skin lesions within a few weeks and total
      restitution within 3 months. During one year no comedons have occurred although
      the local therapeutics are not applied constantly anymore. CONCLUSION: Acne
      comedonica in the radiation area is a rarely known side effect of radiation
      therapy. Although the skin lesions cause no pain or itching they can affect the
      patient due to cosmetic changes. Local treatment with comedolytic acne
      therapeutics is effective.

PMID- 9601476
TI  - [Traveller's diarrhea].

PMID- 9601477
TI  - [Diagnosis of the function of the anorectum and pelvic floor].

PMID- 9601478
TI  - [Help for lactose intolerance: lactose-free food?].

PMID- 9601479
TI  - [Induction of bradycardia by mibefradil in antihypertensive combination therapy].

PMID- 9601481
TI  - Compliant vs non-compliant balloons. A prospective randomized study.
AB  - In this prospective randomized trial we explored the possibility of different
      procedural outcomes with regard to compliant (polyolefin copolymer (POC)), and
      non-compliant (polyethylene terapthelate (PET)) balloon materials commonly used
      during percutaneous transluminal coronary angioplasty (PTCA). For this purpose,
      51 female and 149 male (total 200) patients were randomized to 100 compliant and
      100 non-compliant balloons. Only single lesions were included in the study and
      patients who had PTCA for more than one lesion in different segments at different
      sessions were each entered separately (there were actually 49 female and 143 male
      patients). PTCA procedures were performed in conjunction with quantitative
      coronary angiographic techniques and the films were reviewed by two investigators
      in a blinded fashion. Statistical analysis for various procedural end-points were
      performed by non-paired Student t test with statistical significance being p <
      0.05. There were no differences in demographic and clinical characteristics
      between groups. Lesion characteristics of both groups were exactly matching for
      vessel size, balloon size, balloon vessel ratio, minimal luminal diameter and
      percent stenosis of the index lesion. Similarly, minimal residual diameter,
      percent residual stenosis, net gain, densitometric net area gain, and maximum
      pressure (2.2 +/- 5 mm vs 2.1 +/- 0.6 mm, 18 +/- 17% vs 23 +/- 15%, 0.8 +/- 0.5
      mm vs 0.8 +/- 0.6 mm, 48 +/- 25% vs 48 +/- 26%, 7.3 +/- 2 atm. vs 6.8 +/- 3 atm.,
      respectively) values were not statistically different between compliant and non
      compliant balloon groups. Major in-hospital complications, dissections caused by
      the study balloon (mostly type A and B), crossover and bail-out procedures (5 vs
      3, 34 vs 32, 4 vs 3, 13 vs 14, respectively) were similar for both compliant and
      non-compliant balloon groups. Study balloon success rate (defined as < 50%
      residual stenosis or > 20% net gain in the absence of major in-hospital
      complications, crossovers and bail-outs) and overall procedural success rate (80%
      vs 74%, 90% vs 85%) were not statistically different for compliant and non
      compliant balloons. In conclusion, we did not observe any statistically
      significant difference between compliant and non-compliant balloons in terms of
      immediate procedural results.

PMID- 9601480
TI  - Changes in intracellular Ca2+ mobilization and Ca2+ sensitization as mechanisms
      of action of physiological interventions and inotropic agents in intact
      myocardial cells.
AB  - Physiological and pharmacological interventions are used to regulate cardiac
      contractile functions via modulation of Ca2+ signaling. The relevant regulatory
      mechanisms have recently been assessed in detail by use of novel experimental
      procedures, which include simultaneous measurements of intracellular levels of
      Ca2+ ions and contractile force in intact myocardial preparations loaded with the
      intracellular Ca2+ indicator aequorin and fluorescent dyes, namely, fura-2, indo
      1 and fluo-3. Association with or dissociation from intracellular Ca2+ transients
      of contractile activity is taken as evidence that reflects the primary mechanism
      of action of individual inotropic interventions. In addition, motility assays of
      actin-myosin interactions in vitro have made it possible to define the site of
      action of Ca2+ sensitizers as troponin C and the interaction of the troponin
      tropomyosin complex with actin or the actin-myosin interface at crossbridges.
      Frank-Starling mechanism operates at the level of the binding of Ca2+ ions to
      troponin C and subsequent regulatory processes, while the force-frequency
      relationship is mainly ascribed to an alteration in the intracellular
      mobilization of Ca2+ ions. Cardiotonic agents can be classified as follows: 1)
      agents that act via a cyclic AMP-dependent or a cyclic AMP-independent mechanism;
      and 2) agents that facilitate the intracellular mobilization of Ca2+ ions or
      increase in myofibrillar sensitivity to Ca2+ ions. Regulatory mechanisms mediated
      via the phosphorylation of functional proteins induced by cyclic AMP, which is
      responsible for the actions of novel cardiotonic agents, beta 1-adrenoceptor
      partial agonist and selective inhibitors of phosphodiesterase (PDE) III, have
      currently been clarified in more detail. Ca2+ sensitizers are of extreme
      therapeutic interest because of their ability to increase myocardial
      contractility without an increase in activation energy; they are devoid of risks
      of arrhythmogenicity and myocardial cell death from intracellular Ca2+ overload;
      and they effectively reverse contractile dysfunction under pathophysiological
      situations, such as acidosis or myocardial stunning.

PMID- 9601482
TI  - Directional coronary atherectomy versus coronary angioplasty in vessels larger
      than 3 mm in diameter.
AB  - It has been proposed that directional coronary atherectomy (DCA) should be an
      intervention of choice in larger vessels as one can achieve a greater minimal
      luminal diameter with DCA than with percutaneous transluminal coronary
      angioplasty (PTCA). This in turn should translate into a higher success rate and
      may even reduce the restenosis rate. The aim of this study was to compare DCA
      versus PTCA in vessels > 3 mm in diameter. One hundred fifty consecutive patients
      who met the inclusion criteria and had DCA were compared to 150 similarly
      selected PTCA patients. PTCA patients were selected from the era immediately
      preceding the advent of DCA so that selections bias could be excluded. All
      patients with ostial lesions, restenosis, vessels < 3 mm in diameter, and vessels
      with more than two significant lesions were excluded. Distal segments and
      circumflex cases were excluded as they formed a small subsegment. Both groups
      were similar in terms of demographic, clinical and angiographic variables.
      Quantitative analysis showed that the initial net gain was significantly greater
      in the DCA group than in the PTCA group (2.36 +/- 0.8 mm vs. 1.78 +/- 0.7 mm; p <
      0.05). Residual stenosis was 11% with DCA compared to 33% with PTCA (p < 0.05).
      Despite these improved anatomical results the procedural success rates were
      similar (91.5% vs 84%). Major in hospital complications (death, acute occlusion,
      MI, emergency CABG, re-do) were higher in the DCA group than in the PTCA group
      (12% vs 6%). Clinical follow-up on 276 patients (150 DCA vs 126 PTCA) showed a 6
      month clinical restenosis rate of 18% vs 28%, respectively. The incidence of re
      do in 24 hours for acute occlusion was 6% for DCA and 1% for PTCA. In large-sized
      vessels DCA results in a lower restenosis rate. However, despite a lower
      incidence of residual stenosis, the complication rate tends to be higher with DCA
      (p < 0.05).

PMID- 9601483
TI  - Long-term outcome in triple-vessel coronary artery disease in medically treated
      Japanese patients.
AB  - The long-term outcome in 198 patients with triple-vessel disease (TVD) treated
      medically was investigated. The patients, who underwent coronary angiography
      between September 1973 and February 1984, had significant (75% or more) stenotic
      lesions in all three major coronary arteries. The mean follow-up period was 8.4
      years. The 5- and 10-year survival rates were 80.7% and 64.2%, respectively.
      Cardiac death occurred in 73 patients (36.9%) and nonfatal cardiac events
      developed in 60 patients (30.9%) during follow-up. When cardiac death and
      nonfatal myocardial infarction (MI) were defined as cardiac events, the annual
      attrition rate was 4.7%. There was no difference in survival with regard to the
      presence or absence of MI, the site of infarction, or the presence of total
      occlusion. In the AP group, however, the survival rate decreased as the number of
      totally-occluded arteries increased. In the MI group, the survival rate was not
      altered by the number of totally-occluded arteries, but was affected by the
      ejection fraction (EF). The 5-year survival rate was better in patients with good
      left ventricular function (EF > or = 60%) than in those with impaired left
      ventricular function (EF < 60%), although the 10-year survival rate was similarly
      low in both groups. Revascularization such as PTCA or CABG might improve the long
      term outcome in patients with TVD.

PMID- 9601484
TI  - Comparison of class II and class III activity of dl-sotalol in healthy
      volunteers.
AB  - Racemic sotalol has demonstrated anti-arrhythmic properties which include Class
      II (beta blockade) and Class III (potassium channel blockade) activity. The Class
      II activity is demonstrated primarily in l-sotalol, and Class III activity is
      almost equipotent in each isomer. Class II and Class III activity of dl-sotalol
      was investigated following repeated oral administration (80 mg b.i.d.) for 7
      days. Class II activity was evaluated according to the low frequency spectral
      power obtained by fast Fourier analysis of the R-R interval variation. Class III
      activity was evaluated according to the change in the QTc interval of the surface
      electrocardiogram. The low frequency spectral power decreased after
      administration of the first dose on day 1 and this trend continued throughout the
      duration of the study. The QTc interval did not change with dl-sotalol
      administration. These findings may suggest that Class II activity is more potent
      than Class III activity.

PMID- 9601485
TI  - Angiotensin II type 1 receptor gene polymorphisms in patients with cardiac
      hypertrophy.
AB  - Chronic mechanical stress of the heart secondary to arterial hypertension is a
      primary cause of left ventricular hypertrophy (LVH). The renin-angiotensin system
      (RAS) plays an important role in the cardiovascular system, regulating the
      expression of cardiac hypertrophy, in part, independent of the effects of
      systemic hypertension. A major component of RAS is angiotensin converting enzyme
      (ACE), which is upregulated in pressure overload-induced cardiac hypertrophy as
      well as heart failure. In a recent study, we found that the T allele of the M235T
      polymorphism of the angiotensinogen gene in sporadic hypertrophic cardiomyopathy
      (HCM) patients is associated with LVH. The present study was designed to assess
      the contribution of the polymorphisms of the angiotensin II type 1 receptor
      (AGT1R A1166C) genes on development of left ventricular hypertrophy. Patients
      with hypertensive LVH and relatives of HCM without manifesting the disease,
      showed higher C allele frequency compared to patients with HCM (11.3% vs 4.2%,
      chi 2 = 5.3, p < 0.05 and 10.5% vs 4.2%, chi 2 = 5.3, p < 0.05, respectively),
      but healthy controls did not (11.3% vs 7.5%, chi 2 = 1.42, NS and 10.5% vs 7.5%,
      chi 2 = 1.2, NS). The strong interaction between ACE I/D and AGT1R A1166C gene
      polymorphisms has been found in groups of relatives of HCM patients; odds ratio
      associated with ACE D allele was significant in subjects carrying the AGT1R C
      allele (OR = 7.3, 95% CI 1.6-33.1; chi 2 = 7.9, p < 0.02) compared with healthy
      subjects. We conclude that the molecular variant of the AGT1R A1166C gene is not
      contributing to the development of cardiac hypertrophy in hypertensive LVH and
      HCM patients, whereas carriers of both C and D alleles had a four-fold increase
      in the odds ratio for family history of HCM without manifesting the disease.

PMID- 9601486
TI  - Collagen synthesis by cultured cardiac fibroblasts obtained from cardiomyopathic
      hamsters.
AB  - The aim of the present study was to clarify myocardial collagen metabolism in
      cardiomyopathic hamsters and the effects of the angiotensin converting enzyme
      inhibitor, captopril, on collagen synthesis. Cardiac fibroblasts from Bio 14.6
      cardiomyopathic hamsters and from non-cardiomyopathic Flb hamsters were cultured
      and used in the 4th passage. The synthetic activity of collagenous protein from
      the two types of hamsters was determined by measuring 3H-proline uptake, and the
      collagen type was subsequently analyzed by SDS-PAGE in cultured cardiac
      fibroblasts. Also studied were the effects of the angiotensin converting enzyme
      inhibitor captopril (1 microM) on collagen synthesis by cardiac fibroblasts from
      cardiomyopathic hamsters. Twenty five-week-old Bio 14.6 hamsters had
      significantly higher synthetic activity of collagenous protein and rate of
      collagen synthesis compared with 13-week-old Bio 14.6 hamsters or 25-week-old Flb
      hamsters [Bio 14.6(25-week); 12.4 +/- 1.6, Bio 14.6(13-week); 4.8 +/- 0.4, Flb
      (25-week); 8.7 +/- 0.9 cpm/cell, Bio 14.6(25-week); 11.0 +/- 0.9, Bio 14.6(13
      week); 3.9 +/- 0.4, F1b (25-week); 4.8 +/- 0.4%, p < 0.05]. Qualitatively, 25
      week-old Bio 14.6 hamsters had significantly higher synthetic activity of type I,
      III, IV and V collagens compared with 25-week-old F1b hamsters. The synthetic
      activity of type III collagen was increased the most in the cardiomyopathic
      group. Captopril (1 microM) caused a significant decrease in synthetic activity
      of collagenous protein in 25-week-old Bio 14.6 hamsters (12.4 +/- 1.6 cpm/cell-
      >10.9 +/- 1.1 cpm/cell, p < 0.05). Qualitatively, the synthetic activity of type
      III collagen was decreased to about half. Our study revealed enhanced collagen
      synthetic activity in cardiac fibroblasts from Bio 14.6 hamsters. Captopril
      improved collagen metabolism in cultured cardiac fibroblasts from Bio 14.6
      hamsters not only quantitatively but also qualitatively. The mechanism of this
      improvement may be related to the cardiac renin angiotensin system.

PMID- 9601487
TI  - Renal, intestinal, and adrenal responses to sodium loading in Dahl-Iwai salt
      sensitive and salt-resistant rats.
AB  - This study compared renal and intestinal handling of sodium in Dahl-Iwai salt
      sensitive (S) and salt-resistant (R) rats given a normal-salt diet (0.3% NaCl)
      and a high-salt diet (4.0% NaCl). Six-week-old female S and R rats (n = 7 each)
      were given a normal-salt diet for 14 days followed by a high-salt diet for 3
      weeks. Systolic blood pressure was significantly higher in the S rats than in the
      R rats only at the end of the high-salt diet period (170 +/- 5, mean +/- SEM, vs
      152 +/- 1 mmHg, p < 0.01). Daily sodium intake, water intake, urine volume, and
      urinary and fecal excretions did not significantly differ between the R and the S
      rats during the normal- and high-salt diets, except for a slight, although
      significant, decrease in fecal sodium excretion in the S rats as compared with
      the R rats in the 2nd week of the high-salt diet period. After switching from the
      normal-salt diet to the high-salt diet, urinary sodium excretion increased by 17-
      to 18-fold and fecal sodium excretion increased by about 5-fold in the 1st week
      of salt loading. The changes in urinary and fecal sodium excretions did not
      differ significantly between the groups. Cumulative sodium retention was similar
      in the two groups. The aldosterone/creatinine ratio in 24-hr urine, which was
      significantly lower in the S than in the R rats during the normal-salt diet,
      decreased to similar levels in both groups after salt loading, indicating a
      blunted response of aldosterone in the S rats. Thus, there were no discernible
      differences in renal and intestinal handling of sodium between the S and the R
      rats, except for a slight, but significant, difference in fecal sodium excretion
      in the 2nd week of the high-salt period. The results indicate that inappropriate
      suppression of aldosterone or some other mechanism induced by salt loading may be
      involved in blood pressure elevation in Dahl-Iwai S rats.

PMID- 9601488
TI  - Nursing administration research priorities. A national Delphi study.

PMID- 9601489
TI  - A typology of women nurse executives on the managed care battlefield.

PMID- 9601490
TI  - Facilitating change in dementia care. Staff perceptions.
AB  - OBJECTIVES: The authors describe factors that facilitate positive changes in
      dementia care as perceived by long-term care employees. BACKGROUND: Creating
      positive changes in dementia care is a complex undertaking involving multiple
      variables. The perspectives of long-term care employees may provide important
      insight and direction for a successful change process. METHODS: A convenience
      sample of 181 long-term care employees utilized a q-sort methodology to provide
      data for this descriptive study. Results were analyzed using rankings and
      Spearman's rho correlation coefficient. RESULTS: The facility factors most often
      cited as important for making positive changes in dementia care involved
      teamwork, administrative support, staff attitude, and knowledge. There was little
      congruence between facility factors identified as ideal for providing dementia
      care and those identified as actually evident at the subjects place of
      employment. Personal characteristics that were identified as most important for
      facilitating positive changes in dementia care include genuinely liking people
      with dementia, being flexible, kindness, calmness, and having a positive
      attitude. The correlations between ideal and real personal factors were higher
      than for the facility factors. CONCLUSIONS: This study supports the idea that the
      fundamental tenets of good leadership--communication, involvement, and
      empowerment--are foundational for real change in dementia care to be attained and
      sustained.

PMID- 9601492
TI  - The relationship of job satisfaction with organizational variables in public
      health nursing.
AB  - OBJECTIVE: This study examined the relationship of the organizational variables
      of structure, technology, and environment with job satisfaction among public
      health nurses in a southeastern state. BACKGROUND: There is little research on
      the characteristics of the work environment that influence nurses to remain in
      the public health work setting. Prior research in this setting has focused on the
      negative aspects of the nursing positions. These aspects of least desirability
      for the public health nurse provide only a partial view of job satisfaction. To
      decide and plan specific strategies, the nurse administrator must have valid and
      useful information about the positive aspects of job satisfaction of public
      health nurses. METHODS: The researchers distributed a questionnaire to all
      licensed nursing personnel employed by a state public health department. Data
      collection consisted of four tools: 1) structure instrument; 2) technology
      instrument; 3) environmental uncertainty instrument; and 4) McCloskey-Mueller Job
      Satisfaction Scale (MMSS). The sample of 838 public health nurses (response rate
      of 50.6%) included representation from all 13 districts and the central office of
      the public health department. RESULTS: Significant relationships were found
      between job satisfaction and the demographic variables of nurse category
      (registered nurse and licensed practical nurse) and years of experience with the
      public health department. The critical variable for predicting job satisfaction
      in this group of public health nurses was organizational structure (vertical
      participation, horizontal participation, and formalization). Dimensions of
      structure accounted for 41% of the variance in job satisfaction. Structure
      remained the critical predictor of job satisfaction, although the findings do not
      suggest a conclusive model. The three dimensions of technology (instability,
      variability, and uncertainty) and environmental uncertainty assumed significance
      only in concert with each other or with the dimensions of structure. CONCLUSIONS:
      This study contributes to nursing management theory by examining the relationship
      of organizational structure, technology, and environmental uncertainty with job
      satisfaction in public health nurses. This research also has implications for
      nurse administrators in public health for creating more flexible work
      environments and facilitating staff involvement in decision making.

PMID- 9601491
TI  - Implementing the differentiated pay structure model. Process and outcomes.
AB  - OBJECTIVE: A salaried Differentiated Pay Structure (DPS) model based on the work
      of Dr. Virginia Cleland was tested on two units. The project objectives were to:
      1) create a budget-neutral compensation distinction for different competencies
      and educational levels; 2) evaluate the effect of the new salaried model on unit
      costs and pay; 3) determine the effect of the DPS model on job satisfaction,
      organizational commitment, and anticipated turnover; and 4) assess the impact of
      professional commitment, professional practice climate, perception of staffing
      adequacy, and dispositional optimism on job satisfaction, organizational
      commitment, and anticipated turnover. BACKGROUND: Although there has been long
      standing interest in salaried models and reward methodologies, there is a dearth
      of systematic research associated with specific compensation models. METHODS: A
      quasi-experimental, non-equivalent control group design was used to examine the
      effects of the DPS model. RESULTS: Findings demonstrated that nurses were paid
      more under the DPS model, and that they were paid for more hours than they
      actually worked (N = 68). No difference in job satisfaction was found between
      experimental and control groups. For all nurses (N = 232) dispositional optimism
      was associated with all job satisfaction subscales except pay. Organizational
      commitment, professional commitment, professional practice climate, and staffing
      adequacy were also correlated with job satisfaction, perceptions of care quality
      and anticipated turnover. Older nurses who had worked longer in nursing, and who
      had more tenure were less satisfied with their coworkers and care quality.
      CONCLUSION: Further longitudinal research with larger experimental samples is
      required in order to fully understand the effects of the DPS model in nursing.

PMID- 9601493
TI  - Sources of satisfaction in hospital nursing practice. A guide to effective job
      design.
AB  - OBJECTIVE: As the healthcare system restructures, changes are being made that
      appear to influence nurses' jobs and satisfaction, yet little is known about
      effects on job characteristics and related outcomes. The authors present findings
      from a research project designed to identify links between specific aspects of
      hospital staff nurse (SN) practice and perceived job characteristics and
      psychological states, thought to have motivational consequences. BACKGROUND: The
      Job Characteristics Model (JCM) is the dominant paradigm in contemporary job
      design theory and research. Although generally well-supported, the JCM has
      limitations that constrain its usefulness: first, the Job Diagnostic Survey used
      to assess perceived characteristics does not indicate the specific aspects of
      activities that lead to these perceptions, and second, the JCM, based primarily
      on manufacturing research, does not include interpersonal job characteristics
      that seem important in human service jobs. METHODS: Two studies were conducted
      using a similar methodology. Focus groups of SNs were held to identify links
      between specific activities and characteristics and sources of satisfaction in
      SNs' job content. The Staff Nurse Job Characteristics Index (SNJCI) was developed
      to assess the presence of certain elements and activities in a nurse's job. An
      initial sample of 63 and a second sample of 146 SNs from Medical/Surgical and
      Coronary Care units completed the SNJCI, the JDS, and a demographic form through
      a mail survey. RESULTS: Internal consistency reliabilities (Cronbach's alpha) for
      eight of the nine SNJCI scales were acceptable. Correlation analysis indicates
      that job characteristics are meaningfully related to psychological states and job
      satisfaction. Findings support the hypothesis that specific aspects of SNs' jobs
      are reliably related to characteristics. CONCLUSIONS: Aspects of SNs' jobs
      important to their satisfaction include continuity in nurse-patient
      relationships, authority to initiate independent nursing actions, individual
      accountability for clinical outcomes, and regular performance feedback from
      managers.

PMID- 9601494
TI  - Adverse patient occurrences as a measure of nursing care quality.
AB  - OBJECTIVE: The purpose of this study was to describe relationships among adverse
      patient occurrences aggregated at the unit level of measurement. Relationships
      between adverse occurrences and a patient acuity measure were also described.
      BACKGROUND: Adverse patient occurrence data have been traditionally a major
      indicator of quality care in hospitals; however, few studies have examined
      relationships among these indicators or the usefulness of these indicators for
      assessing the quality of nursing care. METHODS: A correlational design was used
      to examine and describe patterns of relationships among in-patient units in a
      tertiary care hospital. The results demonstrated positive correlations between
      medication error rates and patient falls; these adverse occurrences correlated
      negatively with pressure ulcers, infections, patient complaints, and death.
      Pressure ulcers, infections, patient complaints and death intercorrelated
      positively and also related positively to patient acuity levels. RESULTS: An
      examination of these same rates for a subset of units with similar patient acuity
      levels revealed that most of the interrelationships among the entire set of
      adverse occurrence indicators were positive. When patient acuity was taken into
      account, these adverse outcomes appeared to indicate some common underlying
      characteristic of the units, such as quality of nursing care. CONCLUSIONS: This
      study suggests a relationship between the adverse occurrences that were
      correlated (pressure ulcers, patient complaints, infection, and death) and the
      severity of patient illness. Medication error rates and patient fall rates were
      not correlated with patient acuity and are more likely to indicate quality of
      nursing care across all types of units.

PMID- 9601495
TI  - The first strand transfer during HIV-1 reverse transcription can occur either
      intramolecularly or intermolecularly.
AB  - Reverse transcription is a complicated process that involves at least two cDNA
      transfer reactions to produce a full-length copy DNA of the retroviral RNA
      genome. Because one retrovirus particle contains two identical genomic RNA
      molecules, the transfers can occur in an intramolecular or intermolecular manner.
      The mechanism of the first transfer step (minus-strand strong-stop cDNA transfer)
      has been studied previously in detail in transduction experiments with spleen
      necrosis virus vectors containing genetic markers. Different results have been
      reported with respect to the type of strand transfer mechanism. In this study, we
      analyzed the first strand transfer for human immunodeficiency virus type 1 (HIV
      1). Two genetically marked genomes were copackaged into virions and reverse
      transcription was initiated within these particles upon permeabilization by NP-40
      and addition of dNTPs. To test whether intrastrand or interstrand transfer had
      occurred, the cDNA products of this endogenous reverse transcription reaction
      were extracted from the virions and analyzed for the presence of restriction
      enzyme recognition sites provided by the genetic markers. The results of this
      analysis demonstrated that the first DNA transfer reaction occurs in a random
      manner, with approximately the same contribution of intrastrand and interstrand
      transfers. The ability to perform intermolecular strand transfer was lost upon
      extraction of the dimeric RNA template from the virion particle.

PMID- 9601496
TI  - Oral delivery of homologous and heterologous strains of rotavirus to BALB/c mice
      induces the same profile of cytokine production by spleen cells.
AB  - In this work, we wanted to clarify if differences in antibody (Ab) and
      particularly in secretory immunoglobulin A (IgA) responses following homologous
      or heterologous rotavirus infection could be explained by different priming of
      specific T helper (Th) cells. We compared the Ab responses from suckling BALB/c
      mice orally inoculated with either a heterologous simian (SA11) or bovine (RF)
      rotavirus or a homologous murine rotavirus (EHPw), as well as the profile of
      cytokines produced by spleen cells after in vitro restimulation. Oral inoculation
      of EHPw and SA11 induced a similar pattern of Ab with mucosal and serum IgA
      associated with serum IgG with equal levels of IgG1 and IgG2a, whereas RF
      elicited a weak humoral response. We found that these strains induced the same
      mixed Th1/Th2 pattern of cytokine production by spleen cells with IFN-gamma and
      IL-5 as well as IL-10, but not IL-2 or IL-4. These findings suggest that the
      induction of immune response is probably not different between these strains.
      Other factors such as the amount of antigen, strain immunogenicity, and other
      cytokines, particularly produced in effector sites, remain to be considered in
      order to better explain the differences in secretory IgA following homologous or
      heterologous rotavirus infection.

PMID- 9601497
TI  - The tyrosine-17 residue of Nef in SIVsmmPBj14 is required for acute pathogenesis
      and contributes to replication in macrophages.
AB  - The variant simian immunodeficiency virus termed SIVsmmPBj14 induces a rapidly
      fatal disease in pig-tailed macaques. The acute pathogenic effects of this virus
      appear to be associated with at least two in vitro characteristics: the ability
      to induce lymphocyte proliferation; and the ability to replicate in unstimulated
      PBMC. Two of the amino acids in Nef of PBj14 (the No. 17 residue, tyrosine, and
      the No. 18 residue, glutamic acid) appear to be linked to the virus' ability to
      induce lymphocyte activation. To further study the effects of these amino acids
      on PBj14-induced pathogenesis, we generated two mutant viruses from our molecular
      clone, PBj6.6, containing either changes in both the No. 17 and No. 18 residues
      (termed PBj6.6YE-RQ), or a single change in the No. 17 residue (termed PBj6.6Y
      R). In vitro analyses of these viruses showed that while their replicative
      abilities in stimulated peripheral blood mononuclear cells (PBMC) were altered,
      they still maintained the ability to replicate in unstimulated PBMC. Replication
      of these viruses in macrophage populations was impaired relative to the wild-type
      virus. Both mutant viruses were unable to induce proliferation of macaque PBMC in
      vitro. Virus derived from PBj6.6Y-R was unable to induce acute disease in
      macaques, but did maintain the ability to induce lymphopenia and intestinal
      lymphoid hyperplasia. These results show that the tyrosine-17 residue of Nef is
      linked to lymphocyte proliferation and disease development, but also suggest that
      the pathogenic characteristics of SIVsmmPBj14 are dependent upon multiple genetic
      determinants.

PMID- 9601499
TI  - Establishment of MAIDS-defective virus-infected B cell lines and their
      characterization.
AB  - Mice inoculated with the murine AIDS (MAIDS)-defective virus develop severe B and
      T cell dysfunctions. The primary event in the development of this disease is the
      infection and polyclonal expansion of the target cells of this defective virus,
      which have been reported to belong to the B cell lineage. To further study the
      central role that these cells play in the development of MAIDS, we attempted to
      establish MAIDS-defective virus-infected B cell lines in vitro. We succeeded in
      establishing two cell lines, SD1 and CSTB5, from the enlarged organs of C57BL/6
      mice inoculated with helper-free stocks of the MAIDS-defective virus. Both cell
      lines are not transplantable in syngeneic C57BL/6 mice or in nude or CD8-/- mice
      and are apparently not malignant. They both belong to the B lineage, as their
      immunoglobulin (Ig) genes, but not the T cell receptor (TcR) beta locus, are
      rearranged, suggesting that they are relatively mature B cells. However, analysis
      of cell surface marker expression by FACS revealed a surface phenotype similar to
      that of pre-B cells (MHC I+, MHC II+, B7.2+, sIgM-, sIgG-, kappa-, B220-, CD5-,
      Thy1.2-, TcR-, CD3-, CD4-, CD8-, Mac-1-, 33D1-). Additionally, the CSTB5 cells
      express CD40 and the SD1 cells express CD43. Both cell lines contain the MAIDS
      defective provirus and express the expected 4.2-kb viral RNA and the
      corresponding Pr60gag protein. The CSTB5 cells are nonproducer, while the SD1
      cell line produces what appears to be an endogenous MuLV. The phenotype of these
      cell lines is very similar to what is known about the target B cells of this
      virus in vivo. These new established cell lines are likely to be useful in
      elucidating the mechanism(s) by which the MAIDS-defective virus causes its target
      B cells to proliferate and induce T cell anergy in infected animals.

PMID- 9601498
TI  - Characterization of age- and dose-related outcomes of duck hepatitis B virus
      infection.
AB  - Experimental inoculation of naive ducks with duck hepatitis B virus (DHBV) can
      lead to one of three outcomes, namely, persistent viremia, transient infection
      with or without viremia, or no evidence of infection. The ability of individual
      ducks to resolve DHBV infection was found to be linked to the age of the duck at
      the time of inoculation and the dose of inoculated virus. (1) In recently hatched
      ducks inoculated intravenously (i.v.) with 4 x 10(4) DHBV DNA genomes, a switch
      from persistent viremia to transient antibody appearance was seen at an age of
      inoculation between 7 and 14 days. A 25-fold increase in the dose of virus (1 x
      10(6) DHBV genomes) delayed this switch by 7 days. (2) When 4-month-old ducks
      were inoculated i.v. with different doses of virus, only those receiving the
      highest dose (2 x 10(11) DHBV genomes) showed viremia and extensive viral
      replication and histological changes in the liver; 2/3 ducks in this group had a
      transient infection, while the third duck had viral replication and histological
      changes in the liver that were still present at day 120 postinoculation (p.i.).
      In all ducks receiving lower doses (1 x 10(3), 1 x 10(6), 1 x 10(9) DHBV genomes)
      antibodies to viral surface and core antigens developed without detectable viral
      replication in the liver on days 6, 9, or 12 p.i. (3) When 10- to 16-month-old
      ducks were inoculated i.v. with 2 x 10(11) DHBV genomes, all showed extensive
      viral replication in hepatocytes and mild to moderate histological changes in the
      liver on days 4 or 6 p.i. In 4/5 ducks viremia was not detected, anti-surface
      antibodies were first detected on day 8 p.i., and viral DNA and antigen were
      cleared from the liver by days 35-47 p.i. The remaining duck became viremic with
      persistence of virus in the liver until at least day 46 p.i. The findings of the
      study are consistent with a model for noncytopathic viruses (R. M. Zinkernagel
      (1996) Science 271, 173-178).

PMID- 9601500
TI  - De novo reverse transcription of HTLV-1 following cell-to-cell transmission of
      infection.
AB  - Analogous to transmission of human T-cell leukemia virus type 1 (HTLV-1) in vivo,
      an in vitro cell-to-cell infection model was established by coculturing MT-2
      cells as virus donors and HUT78 cells as recipients. At a donor:recipient ratio
      of 1:2, cell fusion occurred and a new round of HTLV-1 genome replication was
      initiated in the cocultured cells. Newly synthesized unintegrated viral DNA was
      detected by Southern blot within 4-8 h and then increased between 8 and 48 h
      following cell mixing. The most dominant species of unintegrated viral DNA was
      3.7 kb in size which hybridized to a full-length HTLV-1 DNA probe but not to a
      Kpnl viral DNA fragment that is absent from a defective proviral genome that has
      been previously identified in MT-2 cells. Northern blot analysis showed large
      amounts of viral RNA in the virus donor cells and in the cocultured cells, with a
      3.4-kb species being the most abundant. This 3.4-kb RNA gave a pattern identical
      to that of the 3.7-kb unintegrated viral DNA in hybridization studies using the
      two probes. It seems likely that the unspliced RNA transcript from the defective
      proviral genome in MT-2 cells was effectively reverse transcribed upon initiation
      of cell-to-cell viral transmission to susceptible HUT78 cells. Despite active de
      novo reverse transcription, however, viral RNA levels remained unchanged
      following cell-to-cell transmission of HTLV-1 infection and no viral antigen
      production could be attributed to the newly initiated round of viral genome
      replication. As an abortive infection model this simple cell-to-cell infection
      system warrants more detailed study as it has the potential to provide reliable
      information regarding the early events in HTLV-1 transmission and infection.

PMID- 9601501
TI  - Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55)
      receptor.
AB  - Group B coxsackieviruses are etiologically linked with many human diseases
      including acute myocarditis and associated chronic dilated cardiomyopathy. Well
      established CVB3 cardiovirulent strains (CVB3c(s)) with known phenotypic
      difference have been used to study the pathogenesis of virus-induced heart
      disease. The receptor-binding characteristics of cardiovirulent CVB3 are not
      known, but may represent one mechanism accounting for differences in disease
      virulence. In this study, interactions between CVB3c(s) and the decay
      accelerating factor (DAF or CD55) cell surface receptor were examined. Anti-DAF
      monoclonal antibodies (MAbs) blocked virus binding and infection of susceptible
      HeLa cells. Virus binding was significantly reduced by treatment of these cells
      with phosphatidylinositol phospholipase C enzyme, which rendered them DAF
      deficient CVB3c(s) exhibited a differential propensity for the DAF receptor, as
      several cardiovirulent strains interacted more strongly than others. However,
      virus binding and infection was always most effectively blocked by MAbs directed
      against the SCR 2 and 3 domains of DAF, suggesting that binding occurs at a
      similar site(s) on the molecule for all strains. Virus binding and
      internalization were associated with DAF down-regulation at the cell surface, as
      monitored by flow cytometry analysis. Cardiovirulent CVB3 did not interact with
      molecules functionally and/or structurally related to DAF, including CD35, CD46,
      Factor H, or C4-binding protein. Adenovirus type 2 (Ad2) does not use the DAF
      receptor. However, competitive binding assays between Ad2 and CVB1-6, CVB3c(s),
      anti-DAF MAbs, or DAF-reduced cells indicated that DAF is associated with Ad2
      receptors on the HeLa cell membrane. In summary, this study indicates that DAF is
      an attachment receptor for cardiovirulent CVB3 and that DAF interaction may be
      important in the pathogenesis of CVB-mediated heart disease.

PMID- 9601502
TI  - Postreassortment changes in influenza A virus hemagglutinin restoring HA-NA
      functional match.
AB  - An important function of influenza virus neuraminidase (NA) is the removal of
      sialic acid residues from virion components in order to prevent the aggregation
      of virus particles. In previous communications we have reported that reassortant
      viruses containing the NA gene of A/USSR/90/77 (H1N1) virus and HA genes of H3,
      H4, H10, or H13 subtypes had a tendency to virion aggregation at 4 degrees C and
      that the virion clusters irreversibly dissociated after the treatment with
      bacterial neuraminidase. It was concluded that in such reassortants the removal
      of sialic acid residues is inefficient. Nonaggregating variants of the
      reassortants were selected in the course of serial passages in embryonated
      chicken eggs. In the present paper a reassortant virus, R2, having the HA gene of
      A/Duck/Ukraine/1/63 (H3N8) virus and the other genes of A/USSR/90/77 (H1N1)
      virus, as well as its non-aggregating passage variants and both parent viruses,
      have been studied in order to reveal the presence of unremoved sialic acid
      residues in the virions. An assay of sialic acid content by high-performance
      liquid chromatography with fluorescent detection has revealed the presence of
      sialic acid in the purified virus preparations of A/USSR/90/77 (H1N1) virus and
      the R2 reassortant and its nonaggregating variants, whereas only trace amounts of
      sialic acid have been detected in the A/Duck/Ukraine/1/63 (H3N8) parent virus.
      The data obtained with the use of the labeled "indicator" virus suggest that the
      unremoved sialic acid residues are present at the virion surface. The
      nonaggregating variants have been shown to possess a lower affinity toward high
      molecular-weight sialic acid-containing substrates compared to the initial
      reassortant R2. Sequencing of HA genes has revealed amino acid changes in the
      nonaggregating variants compared to the initial reassortant. One substitution,
      N248D in HA1, is the same in two independently selected nonaggregating variants.
      The presented data suggest that the complete removal of sialic acid residues by
      viral NA from the virion components is not obligatory for the absence of virus
      particle aggregation: the latter may be achieved (in the reassortants and,
      presumably, in the wild-type virus) through a balance between the degree of HA
      affinity toward the sialic acid-containing receptors and the extent of the
      removal of sialic acid residues by NA.

PMID- 9601503
TI  - The movement protein and coat protein of alfalfa mosaic virus accumulate in
      structurally modified plasmodesmata.
AB  - In systemically infected tissues of Nicotiana benthamiana, alfalfa mosaic virus
      (AMV) coat protein (CP) and movement protein (MP) are detected in plasmodesmata
      in a layer of three to four cells at the progressing front of infection. Besides
      the presence of these viral proteins, the plasmodesmata are structurally modified
      in that the desmotubule is absent and the diameter has increased drastically
      (almost twofold) when compared to plasmodesmata in uninfected cells or cells in
      which AMV infection had been fully established. Previously reported observations
      on virion-containing tubule formation at the surface of AMV-infected protoplasts
      suggest that AMV employs a tubule-guided mechanism for intercellular movement.
      Although CP and MP localization to plasmodesmata is consistent with such a
      mechanism, no tubules were found in plasmodesmata of AMV-infected tissues. The
      significance of these observations is discussed.

PMID- 9601504
TI  - Human cells arrest in S phase in response to adenovirus 12 E1A.
AB  - It has previously been shown that following viral infection, Ad5 E1A induces cell
      cycle progression of quiescent rodent cells, leading to DNA synthesis and
      mitosis. Here we have examined the effect of Ad12 E1A on the cell cycle
      characteristics of human cells. Human tumor (A549, KB, and HeLa) cells were
      infected with Ad12 d/620, a mutant virus which has a lesion in the E1B gene and
      essentially expresses only E1A. These infected cells progressed from being
      largely in G1 into S phase, where they arrested. Even up to 96 h postinfection
      (p.i.) the cells remained blocked in S phase. DNA synthesis did, however, proceed
      in Ad12 d/620-infected cells, giving rise to multiple copies of cellular DNA.
      Similar results were obtained when primary human skin fibroblasts were infected,
      although the polyploidy was less marked. The expression of cyclins A, B1, and E
      in the tumor cells increased appreciably in response to E1A. In contrast, there
      was a dramatic reduction in the levels of cyclin D1 and D3. Increases in cyclin
      D1 expression could be detected at very late times p.i. In those cell lines
      expressing low levels of cdc2 and cdk2 an appreciable increase in expression was
      seen soon after Ad12 E1A could be detected. The elevated levels of cyclins A, B1,
      and E were associated with increased protein kinase activity directed against
      histone H1. An increase in cyclin D1-associated kinase activity against Rb1 was
      also observed at late times. This deregulation of the cell cycle was not solely
      dependent on E1A inactivation of Rb, since similar effects were seen in Ad12
      d/620-infected retinoblastoma (Y-79) cells, implicating p107 and p130 in E1A
      mediated changes in cell cycle progression. We propose that the E1A-induced
      levels of cyclins A, B1, and E by Ad12 E1A in human cells may lead to an
      uncoupling of S phase from cell cycle progression.

PMID- 9601505
TI  - Adenovirus death protein, a transmembrane protein encoded in the E3 region, is
      palmitoylated at the cytoplasmic tail.
AB  - The 11.6-K protein of human adenovirus 2 (Ad2), which was recently renamed as
      adenovirus death protein (ADP), is a type III membrane glycoprotein that
      ultimately localizes to the nuclear membrane. ADP is encoded in the E3
      transcription unit of Ad2 and migrates as a set of multiple bands in SDS-PAGE
      with three major forms. The corresponding gene product of adenovirus 5 (Ad5) has
      a slightly lower molecular weight and shows the same pattern in SDS-PAGE. We
      report here the covalent attachment of fatty acids to cysteine residues of ADP.
      In the case of Ad5-ADP all three major forms of this protein can be labeled by
      [3H]palmitic acid, but not by [3H]myristic acid, whereas only two [3H]palmitic
      acid-labeled Ad2-ADP species could be detected. The label is sensitive to
      treatment with 1 M hydroxylamine at pH 7 and with 20% beta-mercaptoethanol
      indicating that the fatty acids are linked via a thioester bond. By thin layer
      chromatography, the vast majority of the incorporated label was identified as
      palmitic acid. Two cysteine residues at the boundary between transmembrane domain
      and cytoplasmic tail which could serve as acceptor sites were mutated to alanine
      residues by site-directed mutagenesis of the cloned Ad5-ADP gene. Expression of
      wild-type Ad5-ADP and the resulting mutants was performed in HeLa cells using the
      vaccinia virus T7 expression system. As demonstrated by labeling with
      [3H]palmitic acid, only the mutants with one remaining cysteine residue in the
      cytoplasmic tail were able to incorporate [3H]palmitic acid, indicating that
      either could serve as acceptor site. In contrast the double cysteine mutant could
      not be labeled by [3H]palmitic acid, clearly demonstrating that cysteines 53 and
      54 are required for palmitoylation and probably represent the palmitoylation
      sites in Ad5-ADP.

PMID- 9601506
TI  - Mice expressing the E7 oncogene of HPV16 in epithelium show central tolerance,
      and evidence of peripheral anergising tolerance, to E7-encoded cytotoxic T
      lymphocyte epitopes.
AB  - In order to derive mice which expressed both the E7 open reading frame transgene
      of human papillomavirus type 16 in skin and MHC class 1 restriction elements for
      several E7-encoded cytotoxic T-lymphocyte (CTL) epitopes, K14.HPV16E7 mice which
      express E7 in basal keratinocytes were crossed to the F1 generation with A2.1 Kb
      transgenic mice which express the MHC binding cleft domains of human HLA A*0201,
      and murine H-2b. F1 mice (denoted K14E7 x A2.1) expressed E7 in the thymus at
      least as early as 2-5 days before birth. Immunisation of FVB x A2.1 control mice
      (transgenic for HLA A*0201 and H-2b but not for E7), with two HLA A*0201
      restricted epitopes of E7 and one H-2b-restricted CTL epitope of E7, gave strong
      primary CTL responses recognising epitope-pulsed or constitutively E7-expressing
      syngeneic target cells. In contrast, in immunised K14E7 x A2.1 mice, the CTL
      responses to the H-2b epitope and one of the HLA A*0201 CTL epitopes were
      strongly down-regulated, and to the other HLA A*0201 epitope, completely
      abolished, as demonstrated by percentage specific killing by bulk splenocyte
      cultures in cytotoxicity assays, and by CTL precursor frequency analysis. In
      thymus-transplanted bone marrow radiation chimeras in which the immune system of
      K14E7 x A2.1 mice was replaced by a FVB x A2.1 immune system, specific
      immunisation did not result in reemergence of strong E7-directed CTL responses.
      In agreement with these in vitro findings, specific immunisation failed to
      significantly alter the course of E7-associated tumour development in K14E7 x
      A2.1 mice. These data are consistent with a model of central deletional CTL
      tolerance to E7-encoded epitopes recognised in the context of two distinct MHC
      class 1 restriction elements, and with the possibility of peripheral T-cell
      anergy maintained by expression of E7 in the skin.

PMID- 9601507
TI  - The complete genomic sequence of the modified vaccinia Ankara strain: comparison
      with other orthopoxviruses.
AB  - The complete genomic DNA sequence of the highly attenuated vaccinia strain
      modified vaccinia Ankara (MVA) was determined. The genome of MVA is 178 kb in
      length, significantly smaller than that of the vaccinia Copenhagen genome, which
      is 192 kb. The 193 open reading frames (ORFs) mapped in the MVA genome probably
      correspond to 177 genes, 25 of which are split and/or have suffered mutations
      resulting in truncated proteins. The left terminal genomic region of MVA contains
      four large deletions and one large insertion relative to the Copenhagen strain.
      In addition, many ORFs in this region are fragmented, leaving only eight genes
      structurally intact and therefore presumably functional. The inserted DNA codes
      for a cluster of genes that is also found in the vaccinia WR strain and in cowpox
      virus and includes a highly fragmented gene homologous to the cowpox virus host
      range gene, providing further evidence that a cowpox-like virus was the ancestor
      of vaccinia. Surprisingly, the central conserved region of the genome also
      contains some fragmented genes, including ORF F5L, encoding a major membrane
      protein, and ORFs F11L and O1L, encoding proteins of 39.7 and 77.6 kDa,
      respectively. The right terminal genomic region carries three large deletions all
      classical poxviral immune evasion genes and all ankyrin-like genes located in
      this region are fragmented except for those encoding the interleukin-1 beta
      receptor and the 68-kDa ankyrin-like protein B18R. Thus, the attenuated phenotype
      of MVA is the result of numerous mutations, particularly affecting the host
      interactive proteins, including the ankyrin-like genes, but also involving some
      structural proteins.

PMID- 9601508
TI  - Adaptation of Theiler's virus to L929 cells: mutations in the putative receptor
      binding site on the capsid map to neutralization sites and modulate viral
      persistence.
AB  - Persistent strains of Theiler's virus, a murine picornavirus, produce a life-long
      infection of the central nervous system of the mouse and induce a chronic
      demyelinating disease. Strain DA1, a molecular clone of such a persistent strain,
      produces a prominent cytopathic effect in BHK-21 cells but is less efficient at
      infecting L929 cells. We cloned the cDNA of a derivative of virus DA1, adapted to
      promote a rapid cytopathic effect in L929 cells. Adaptation of the new variant
      (named KJ6) to L929 cells correlated with an enhanced viral entry rather than
      with an increased replication rate of the genome. Mutations responsible for L929
      cells adaptation occurred in amino acids exposed at the surface of the capsid, in
      the CD loop of VP1 (100-102) and in the EF loop of VP2 (162-171-173), suggesting
      that these residues could be involved in receptor recognition. These two clusters
      of amino acids are precisely known to be part of neutralization epitopes. They
      also differentiate persistent from neurovirulent strains of Theiler's virus.
      Adaptation of the virus to L929 cells was accompanied by attenuation of its
      virulence for the mouse. Taken together, these data suggest a close relationship
      between receptor binding, virus neutralization, and virus phenotype.

PMID- 9601509
TI  - Cell-to-cell movement of turnip crinkle virus is controlled by two small open
      reading frames that function in trans.
AB  - Previous studies on turnip crinkle virus (TCV) have suggested that the two small,
      centrally located ORFs, conserved in all Carmoviruses, are both required for cell
      to-cell movement (Hacker et al., 1992). We now demonstrate that the cell-to-cell
      movement of TCV is mediated by in trans complementation of the two proteins.
      First, both of the putative movement proteins (MPs p8 and p9) were shown to be
      translated in vitro from transcripts representing the 1.7-kb subgenomic RNA.
      Western blot analysis, using antisera prepared against GST fusion proteins of
      both genes, was then used to show that the p8 but not the p9 protein accumulated
      to detectable levels in particulate fractions of infected cells. Cell-to-cell
      movement of various MP mutants in Arabidopsis was evaluated by in situ
      hybridization of inoculated leaves. Changes in either of the two MP genes
      resulted in failure of the mutants to move cell-to-cell. Coat protein was found
      to be unnecessary for cell-to-cell movement. Complementation of cell-to-cell
      movement by co-inoculating p8-defective mutants with a p9-defective mutant
      resulted in delayed systemic infection. In contrast, efficient cell-to-cell
      movement was achieved when the MP mutants were inoculated into transgenic plants
      expressing the corresponding functional gene(s). These experiments provide
      further evidence that both MP genes encoded by Carmoviruses must function in
      trans in the same cell in order to mediate cell-to-cell movement.

PMID- 9601510
TI  - Detection of subgenomic cDNAs and mapping of feline foamy virus mRNAs reveals
      complex patterns of transcription.
AB  - Feline foamy virus (FeFV) belongs to the group of spumaretroviruses that contain
      in addition to gag, pol, and env accessory genes collectively called bel genes.
      Primate FVs have been shown to utilize internal promoters in addition to the 5'
      LTR promoters. In contrast to other known retroviruses, the FV pol genes are
      expressed via spliced transcripts. Northern blot analysis and reverse
      transcription-coupled polymerase chain reactions (RT-PCR) were used to amplify,
      clone, and characterize cDNAs generated from subgenomic viral transcripts.
      Sequencing of the splice site junctions of the different FeFV mRNAs showed that
      singly and multiply spliced subgenomic transcripts were expressed in virus
      infected cells. The relative amount of the spliced pol-specific transcripts was
      quantitated and FeFV pol mRNA found to be expressed at about one-half of that of
      the genomic mRNA. The major FeFV internal start site of transcription was
      identified at RNA position 7925. Comparison of the FeFV transcriptional patterns
      to those of the human foamy virus revealed that the FeFV bel 1 mRNA was expressed
      exclusively from the internal promoter in contrast to primate foamy viruses that
      use both the LTR and the internal promoter for Bel 1 expression. Unexpectedly, an
      env-bel 2 mRNA was identified in FeFV-infected cells. In addition, cDNAs from
      FeFV-infected cells were directly amplified by PCR without RT reactions and found
      to correspond to genomic and to a subset of different subgenomic FeFV mRNAs.

PMID- 9601511
TI  - Role of a subdominant H-2Kd-restricted SV40 tumor antigen cytotoxic T lymphocyte
      epitope in tumor rejection.
AB  - SV40-transformed mKSA cells (H-2d) readily induce progressively growing tumors in
      adult syngeneic BALB/c mice while expressing the full complement of H-2d MHC
      class I antigens. BALB/c mice previously immunized with SV40, soluble SV40 T
      antigen, or irradiated SV40-transformed syngeneic, allogeneic, or xenogeneic
      cells reject an mKSA tumor challenge even though these mice have been considered
      low- or nonresponders to T antigen due to difficulty in demonstrating SV40 T
      antigen-specific CTL. We have investigated the role of H-2d-restricted CTL in the
      rejection of SV40 tumors in BALB/c mice. Immunization of BALB/c mice with SV40
      induced T antigen-specific CTL which were largely. H-2Ld-restricted. However,
      following repeated in vitro restimulation with mKSA cells, CTL emerged which
      recognized a subdominant H-2Kd-restricted epitope corresponding to T antigen
      residues 499-507. Immunization of BALB/c mice with a recombinant vaccinia virus
      expressing the T499-507 epitope provided partial protection against a challenge
      of syngeneic mKSA tumor cells and induced the generation of T499-507-specific
      CTL. These results indicate that a subdominant H-2Kd-restricted CTL epitope can
      participate in the rejection of SV40 tumors in BALB/c mice.

PMID- 9601512
TI  - The exonuclease activity of HSV-1 UL12 is required for in vivo function.
AB  - The herpes simplex virus type 1 (HSV-1) UL12 gene encodes an alkaline pH
      dependent deoxyribonuclease termed alkaline nuclease. A recombinant UL12 knockout
      mutant, AN-1, is severely compromised for growth, and analysis of this mutant
      suggests that UL12 plays a role in processing complex DNA replication
      intermediates (R. Martinez, R. T. Sarisky, P. C. Weber, and S. K. Weller, (1996)
      J. Virol. 70, 2075-2085). This processing step may be required for the generation
      of capsids that are competent for egress from the nucleus to the cytoplasm. In
      this report, we address the question of whether the AN-1 growth phenotype is due
      to the loss of UL12 catalytic activity. We constructed two point mutations in a
      highly conserved region (motif II) of UL12 and purified wild-type and mutant
      enzymes from a baculovirus expression system. Both mutant proteins are stable,
      soluble, and competent for correct nuclear localization, suggesting that they
      have retained an intact global conformation. Neither mutant protein, however,
      exhibits exonuclease activity. In order to examine the in vivo effects of these
      mutations, we determined whether expression of mutant proteins from amplicon
      plasmids could complement AN-1. While the wild-type plasmid complements the
      growth of the null mutant, neither UL12 mutant can do so. Loss of exonuclease
      activity therefore correlates with loss of in vivo function.

PMID- 9601513
TI  - Molecular and in vitro analysis of eight dengue type 2 viruses isolated from
      patients exhibiting different disease severities.
AB  - Potential genetic determinants of dengue virulence were studied by sequencing the
      entire genomes of eight dengue 2 virus strains isolated from patients exhibiting
      different disease severities during an epidemic season in northeastern Thailand
      in 1993. The isolates came from one dengue shock syndrome (ThNH-7/93), three
      dengue hemorrhagic fever, and four dengue fever patients. Phylogenetic analysis
      showed that the isolates belonged to the Southeast Asian genotype. The 3'
      noncoding regions showed distinctive secondary structures, with one specific
      structure for the isolate ThNH-7/93. Analysis of the predicted polyprotein showed
      several amino acid (aa) changes scattered mostly in the nonstructural region. Of
      30 positions with aa changes, 7 were unique to the isolate ThNH-7/93 and 3 of
      those led to radical alterations in aa character. Several aa changes coincided
      with previous studies relating genome sequence and virulence. Minimal changes in
      computer-predicted protein secondary structures were observed. Infective
      particles in the inoculum for all isolates were approximately equal as measured
      by focus formation on BHK-21 cells, but this did not correlate with the number of
      plaques formed on LLC-MK2 cells. Isolates from patients that experienced
      secondary infection were shown to have significantly larger plaques than the
      isolates from primary infection patients.

PMID- 9601514
TI  - High SDF-1 expression in HIV-1 carriers does not correlate with CD8+ T-cell
      mediated suppression of viral replication.
AB  - Stromal cell-derived factor 1 (SDF-1) inhibits T-cell tropic (T-tropic) HIV-1
      infection in vitro. In this study, we examined the regulatory role of SDF-1 on
      HIV-1 replication in peripheral blood mononuclear cells (PBMC) of HIV-infected
      individuals. We found that the amount of SDF-1 mRNA in freshly isolated PBMC of
      HIV-1 carriers was higher than in healthy donors. Moreover, PBMC from some
      asymptomatic carriers (ACs) exhibited high levels of SDF-1 mRNA expression. The
      level of SDF-1 expression in PBMC did not correlate with the magnitude of CD8+ T
      cell-mediated suppression of HIV-1 among ACs SDF-1 inhibited HIV-1 replication at
      the viral entry step, whereas a single-cycle HIV-1 infection system showed that
      the major part of the CD8+ T-cell-mediated suppression occurs after intracellular
      penetration of the virus. Our results suggest that SDF-1 acts as a suppressor of
      virus replication in a CD8+ T-cell-independent mechanism in HIV-infected
      individuals.

PMID- 9601515
TI  - Subcellular localization of human immunodeficiency virus type 1 RNAs, Rev, and
      the splicing factor SC-35.
AB  - The HIV-1 protein Rev regulates the cytoplasmic levels of incompletely spliced
      HIV-1 mRNAs. The plasmid pSVc21, which contains a HIV-1 provirus, was introduced
      into COS cells by transient transfection. Simultaneous detection of HIV-1 RNAs
      and Rev proteins produced in transfected cells was then performed in order to
      determine the relative distribution of these two components. HIV-1 RNAs and the
      Rev protein localized to the same areas of the nucleoplasm, implying that these
      locations represent sites where Rev interacts with its target RNAs. Using a
      monoclonal antibody targeted to the splicing factor SC-35 it was demonstrated
      that the sites where HIV-1 mRNAs and Rev were detected often contained weak anti
      SC-35 staining, whereas little RNA and Rev were found in strongly labeled SC-35
      containing speckles. The same distribution of HIV-1 RNAs relative to SC-35 was
      also seen in transfected HeLa cells and in primary human lymphocytes infected
      with HIV-1 primary isolates. In addition, transiently expressed intron-containing
      beta-globin RNAs were shown to distribute to weak anti-SC-35 staining in a manner
      similar to that of HIV-1 RNAs. The findings suggest that Rev and HIV-1 RNAs
      interact at putative sites of mRNA transcription and splicing.

PMID- 9601516
TI  - Roles in cell-to-cell fusion of two conserved hydrophobic regions in the murine
      coronavirus spike protein.
AB  - The spike (S) protein of coronavirus mouse hepatitis virus (MHV), mediates
      attachment and fusion during viral entry and cell-to-cell fusion later in
      infection. By analogy with other viral proteins that induce cell fusion the MHV S
      protein would be expected to have a hydrophobic stretch of amino acids that
      serves as a fusion peptide. Sequence analysis suggests that the S protein falls
      within the group of fusion proteins having internal rather than N-terminal fusion
      peptides. Based on the features of known viral fusion peptides, we identified two
      regions (PEP1 and PEP2) of MHV-A59 S2 as possible fusion peptides. Site-directed
      mutagenesis and an in viro cell-to-cell fusion assay were used to evaluate the
      roles of PEP1 and PEP2, as well as a third previously identified putative fusion
      domain (PEP3) in membrane fusion. Substitution of bulky hydrophobic residues with
      charged residues within PEP1 affects the fusion activity of the S protein without
      affecting processing and surface expression. Similar substitutions within PEP2
      result in a fusion-negative phenotype; however, these mutant S proteins also
      exhibit defects in protein processing and surface expression which likely explain
      the loss of the ability to induce fusion. Thus PEP1 remains a candidate fusion
      peptide, while PEP2 may play a significant role in the overall structure or
      oligomerization of the S protein. PEP3 is an unlikely putative fusion peptide
      since it is not conserved among coronaviruses and nonconservative amino acid
      substitutions in PEP3 have minimal effects on cell-to-cell fusion.

PMID- 9601517
TI  - Mapping of ORF121, a factor that activates baculovirus early gene expression.
AB  - The protein product of the 39k gene of Autographa californica nuclear
      polyhedrosis virus is thought to be important for viral replication because of
      its association with the virogenic stroma and its role in activation of late gene
      expression Transient expression assays showed that addition of a DNA fragment
      encoding a 58-amino-acid polypeptide increased expression of a 39k reporter
      plasmid. This stimulation was dependent on cotransfection of a plasmid encoding
      IE1. Cotransfection of this gene, orf121, also stimulated ie1 expression, and the
      activation of ie1 was even more dramatic in the presence of IE1. These data
      suggested that ORF-121 stimulated 39k expression by upregulation of IE1
      expression. Activation of 39k by ORF121 and the viral transcription factor IE2
      was additive, while activation by ORF-121 and the apoptotic suppressor P35 was
      synergistic. Cotransfection of p39cat and pIE1 with plasmids encoding ORF121,
      IE2, and P35 stimulated 39cat expression more than 100-fold compared to cells
      transfected with only p39cat and pIE1. These data suggest that IE2 and ORF121
      work by similar mechanisms and indirectly activate p39cat by increasing IE1
      expression, while P35 increases 39cat expression by a different mechanism.

PMID- 9601518
TI  - Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication
      among HCV seroconverters.
AB  - The objective of this retrospective cohort study is to assess the mechanism by
      which human immunodeficiency virus type 1 (HIV) influences hepatitis C virus
      (HCV) replication in injecting drug users. Virological (HCV and HIV RNA levels)
      and immunological (CD4+, CD8+ cell counts, and anti-CD3 reactivity) parameters
      were determined in 19 HCV seroconverters in sequential samples over a period of 1
      to 9 years. Among these subjects, 10 were HIV-seronegative (HIVneg), 4 were HIV
      seropositive (HIVpos), and 5 seroconverted for HIV (HIVsc) during the observation
      period. HCV RNA levels were higher in HIVpos subjects than in HIVneg subjects. In
      subjects seroconverting for HIV, HCV, RNA levels increased significantly
      immediately after HIV seroconversion (P < 0.0001), while they remained stable
      over time in HIVpos and HIVneg subjects. HCV RNA correlated inversely with CD4+
      cell counts in both the HIVpos population (R = -0.22, P < 0.05) and the HIVneg
      population (R = -0.45, P < 0.0001). In addition, when subjects were stratified
      according to CD4+ cell counts a significant difference was found in HCV RNA
      levels between HIVpos and HIVneg subjects with CD4+ cell counts > 500
      cells/microliter (P = 0.001), but not in the population with CD4+ cell counts <
      500 cells/microliter. In no population was a correlation found between HCV RNA
      levels and CD8+ cell counts or anti-CD3 reactivity. Both HIV infection and CD4+
      cell counts are apparently associated with HCV RNA levels. The direct
      association, independent of CD4+ cell counts, between HIV infection and HCV
      replication appears to be stronger than the association between HIV-induced CD4+
      cell decline and HCV replication. We conclude that (i) HCV replication is in some
      way directly influenced by the presence of HIV; (ii) HCV-specific host immunity
      controls, in part, HCV replication; and (iii) HCV replication increases when the
      immune system is impaired by HIV.

PMID- 9601519
TI  - Transmission of hepatitis C virus infection to tree shrews.
AB  - Although hepatitis C virus (HCV) infection can be reproduced in chimpanzees,
      these animals are rare and expensive. Tree shrews (tupaias) are small animals,
      closely related to primates, which adapt easily to a laboratory environment. In
      this work we have investigated the susceptibility of Tupaia belangeri chinensis
      to HCV infection. Tupaias caught in the wild in Yunnan (China) were inoculated in
      China with HCV genotype 1b (study A) and in Spain with a mixture of genotypes 1b,
      1a, and 3 (study B). In study B tupaias were divided into three groups: group I
      was inoculated without previous manipulation, group II received 750 cGy of X-ray
      whole-body irradiation before inoculation, and group III was used as control.
      Transient or intermittent viremia occurred in 34.8% (8/23) and anti-HCV in 30.4%
      (7/23) of tupaias in study A. In study B a transient viremia was detected in 20%
      (2/10) in group I and in 50% (2/4) in group II. Anti-HCV was found in 1 tupaia
      from group I and in 3 from group II: Viremia lasted for longer and anti-HCV
      tended to reach higher titers in animals which received total body irradiation.
      ALT elevations and nonspecific pathological changes occurred in inoculated
      tupaias; however, the wild nature of the animals precludes the interpretation of
      these changes as solely due to HCV infection. In summary our results show that
      T.b. chinensis are susceptible to HCV and that whole-body irradiation may
      possibly increase the efficiency of the infection. These animals may serve as an
      in vivo system for culturing HCV and addressing pathophysiological and
      therapeutic issues of HCV infection.

PMID- 9601520
TI  - The induction of apoptosis by SV40 T antigen correlates with c-jun
      overexpression.
AB  - Simian virus (SV40) T antigen shares many characteristics with adenovirus E1A
      which is known to induce apoptosis. To verify the potential of SV40 T antigen
      mediated apoptosis, we stably expressed T antigen in immortalized human
      epithelial cells (Z172 and HaCaT). We found that SV40 T antigen could directly
      cause apoptosis in 22-27% of these cells under normal growth condition as
      measured by chromatin condensation and nucleosomal fragmentation. The apoptosis
      of HaCaT cells which contain mutant p53 suggests the p53-independent nature of T
      antigen-mediated apoptosis. T antigen-induced apoptosis was associated with
      increased expression of c-Jun protein. Moreover, the overexpression of c-jun
      alone in these cells also induced apoptosis, indicating that c-jun might play an
      important role in T antigen-induced apoptosis.

PMID- 9601521
TI  - The bis-azo compound FP-21399 inhibits HIV-1 replication by preventing viral
      entry.
AB  - The bis-azo compound FP-21399 inhibits HIV-1 infection. We now show that FP-21399
      acts on the HIV-1 envelope glycoprotein to prevent viral replication. This
      compound targets the entry step of the HIV-1 replication cycle as demonstrated by
      time-of-addition and single cycle viral entry assays. The entry of SIVmac239,
      which uses the same coreceptors (CD4/CCR5) as HIV-1, was not inhibited by FP
      21399, indicating that the antiviral effect of FP-21399 is specific for the HIV-1
      envelope glycoprotein and is not dependent upon the cellular receptors CD4 and
      CCR5. FP-21399 inhibits neither the activity of HIV-1 reverse transcriptase nor
      the expression of HIV-1 early mRNA. Finally, this compound inhibits gp120
      shedding of the T-tropic virus. Our results suggest that the anti-HIV activity of
      FP-21399 is due to its interaction with HIV-1 gp120/41 complex during viral
      entry.

PMID- 9601522
TI  - Production of HIV-1 by human B cells infected in vitro: characterization of an
      EBV genome-negative B cell line chronically synthetizing a low level of HIV-1
      after infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) has tropism for helper T lymphocytes
      and cells of the monocyte/ macrophage lineages. HIV-1 can also infect other cell
      types, including B cells. We show here that 10% of fresh circulating B cells from
      HIV-1-seronegative donors (i) express the CD4 receptor and CCR5 and CXCR4, two
      recently described coreceptors for HIV-1 and (ii) are permissive to HIV-1 with de
      novo proviral DNA integration following ex vivo infection by either SI (syncytium
      inducing) or NSI (non-syncytium-inducing) isolates. To get further information on
      the interaction between HIV and B cells, the susceptibility of several EBV
      positive or -negative B cell lines to infection by SI and NSI isolates was
      checked. Following infection of an EBV- CD4+ CXCR4+ CCR5- B cell line (DG75) by
      an SI HIV-1 isolate, we obtained a cell line which chronically produced low-level
      infectious HIV-1 for 2 years (HIV-DG75). Immunocytochemical data, combined with
      in situ PCR data, established that HIV-DG75 cells consist of at least three
      populations uninfected cells, infected virus-producing cells, and infected but
      nonproducing cells. Moreover, HIV-DG75 cells which express p24 antigen do not go
      into apoptosis, contrary to T lymphocytes. We infer from these results that B
      cells could constitute a reservoir of infectious virus in infected patients.

PMID- 9601523
TI  - Improved envelope function selected by long-term cultivation of a translation
      impaired HIV-1 mutant.
AB  - The untranslated leader region of the human immunodeficiency virus (HIV) RNA
      genome contains multiple regulatory elements that fold into stable hairpin
      structures. Because extensive secondary structure can block the scanning of
      ribosomes, an alternative mechanism for HIV translation seems feasible. To study
      the mechanism of HIV-1 mRNA translation, a start codon was introduced in the
      leader region that will usurp scanning ribosomes. This upstream AUG mutation
      (uAUG) inhibited HIV gene expression, indicating that HIV-1 mRNA translation
      occurs via the regular scanning mechanism. Revertant viruses with increased
      replication capacity were obtained upon prolonged culturing of the mutant virus.
      To our surprise, the introduced start codon had not been inactivated in these
      phenotypic revertants. Instead, these revertants contain additional mutations in
      the envelope (Env) protein that stimulated HIV-1 replication. These second-site
      Env mutations did not specifically overcome the gene expression defect of the
      uAUG mutant, as the replication capacity of other HIV-1 mutants with an unrelated
      defect could also be improved. The uAUG construct appears to be a unique tool in
      forced HIV-1 adaptation studies because the deleterious uAUG mutation is stably
      maintained in the progeny, yielding phenotypic revertants with second-site
      mutations elsewhere in the viral genome.

PMID- 9601524
TI  - Variability of persisting MHV RNA sequences constituting immune and replication
      relevant domains.
AB  - Survivors of acute infection with the neurotropic JHM strain of mouse hepatitis
      virus develop a persistent infection of the central nervous system associated
      with chronic ongoing demyelination. Persistence is characterized by viral RNA in
      the absence of infectious virus. To associate persistence with possible immune
      evasion and/or replication defects, viral RNA from brains of acutely and
      persistently infected mice was examined for mutations by reverse transcriptase
      PCR. Sequences analyzed included the encapsidation sequence (ECS), the
      transmembrane domains of the matrix (M) protein, and a cytotoxic T cell (CTL)
      epitope within the nucleocapsid (N) protein. The ECS, present only on genomic
      RNA, revealed minimal variability and was detected out to 120 days postinfection,
      suggesting low levels of replication. The M gene sequence also remained stable
      during persistence despite random mutations during the acute phase. Although the
      N gene sequence exhibited the greatest diversity, mutations were random and not
      selected for during persistence. A single exception was detected comprising a
      prominent Pro to Ser substitution in a region of N not associated with any known
      regulatory or immune function. Of the N gene mutations found within the CTL
      epitope in responder mice (H-2d), one resulted in reduced CTL recognition with no
      evidence of antagonist activity. However, this mutation was also detected in
      nonresponder mice (H-2b), suggesting that escape variants arising from CTL
      pressure play no role in establishing persistence in immunocompetent hosts
      infected as adults.

PMID- 9601525
TI  - Preparation of plasmid DNA in transfection complexes for fluorescence and
      electron spectroscopic imaging.
AB  - The aim of this project was to develop procedures necessary to study mechanisms
      of receptor mediated gene transfer by means of integrated microscopy. Plasmid DNA
      was incorporated into a transfection complex consisting of poly(L)lysine and
      transferrin to which the nuclear localization signal was conjugated. This complex
      was presented to cultured glioma cells. Preparation of the transfected DNA for
      imaging was pursued by two methods. In the first method tetramethylrhodamine,
      nanogold, and ferritin were linked through streptavidin to the biotinylated
      plasmid DNA. Trafficking of the fluorescent derivatives was studied in living
      cells with fluorescence microscopy. Then, selected cells were rapidly cryo
      immobilized. Ultra-structural distribution of the transfected DNA was imaged with
      energy filtering transmission electron microscopy. In the second method, the
      unmodified transfected DNA was detected in cryo-immobilized cells by in situ
      polymerase chain reaction and in situ hybridization. For laser scanning
      fluorescence microscopy probes were labeled with tetramethylrhodamine. For
      ultrastructural analysis by electron spectroscopic imaging, probes containing
      incorporated digoxigenin were labeled with anti-digoxigenin boronated antibodies.
      Based upon the developed procedures, it has been demonstrated that the presence
      of the nuclear localization signal in the transfection complex resulted in rapid
      nuclear import of the transfected DNA.

PMID- 9601526
TI  - Simultaneous identification of a specific gene protein product and transcript
      using combined immunocytochemistry and in situ hybridization with non-radioactive
      probes.
AB  - Simultaneous identification of messenger RNA (mRNA) and proteins in the same
      cells or tissues is a valuable tool to help the cell biologist evaluate the cell
      secretory cycle. Some cells may produce the mRNA and delay the production of the
      proteins. Alternatively, the proteins may be rapidly secreted. Other cells may
      produce both in sequence within the same time frame. Because of this difference,
      some cells can only be identified by their mRNA product. Others may have both
      products. This presentation describes a non-radioactive approach to the detection
      of both products with dual-peroxidase labeling protocols in use in this
      laboratory since 1983. The first detection system uses biotinylated cRNA probes
      or oligoprobes in in situ hybridization along with antisera to biotin to detect
      the hybrid. The detection system is amplified by 2-3 layers of anti-biotin,
      second antibody (made against the anti-biotin) and streptavidin conjugated to
      horseradish peroxidase. After the mRNA is detected with a blue-black substrate
      (nickel intensified diaminobenzidine), the antigens are detected with
      immunoperoxidase techniques and orange-amber substrate. The in situ hybridization
      protocol can also be used at the electron microscopic level. Trouble shooting and
      control protocols are also described. This approach has been shown to be valuable
      for detection of pituitary hormones, growth factors mRNAs and antigens.

PMID- 9601527
TI  - In situ hybridization, in situ transcription, and in situ polymerase chain
      reaction.
AB  - In situ hybridization, in situ transcription, and in situ polymerase chain
      reaction (PCR) are techniques used to detect DNA and RNA sequences within a cell
      or tissue structure. These three in situ methodologies employ the principles of
      recombinant DNA to form double-stranded hybrids of DNA-DNA, DNA-RNA, or RNA-RNA.
      The essence of in situ hybridization (ISH) is the hybridization of a labeled
      probe to a complementary target sequence, whereas in situ transcription (IST) is
      the synthesis of complementary DNA incorporating a label directly on the target
      DNA or RNA within a cell or tissue. In the case of in situ PCR (ISPCR), it is the
      repeated in situ duplication of both the sense and antisense strands of DNA to
      increase the number of copies of the target sequence. ISH, IST, and ISPCR each
      have their advantages and disadvantages. The purpose of this chapter is to
      address in situ considerations required of these techniques, emphasizing tissue
      fixation, pre-hybridization steps, DNA probes, RNA probes, oligoprobes, and probe
      labeling. Five successfully used protocols are presented as examples. Any given
      nucleotide target sequence may have its own unique set of optimum conditions,
      thus requiring some adjustment in the hands of the user.

PMID- 9601528
TI  - Preparation of samples for polymerase chain reaction in situ.
AB  - The purpose of this paper is to describe the key variables in sample and reagent
      preparation needed for successful polymerase chain reaction (PCR) in situ. Tissue
      or cell preparations should be fixed in a cross linking fixative, such as 10%
      buffered formalin, preferably from 15 to 48 hours. Tissues should be embedded in
      paraffin; cell preparations can be fixed when near confluence, then physically
      removed and processed. When possible three samples (4 microM tissue sections or 1
      5000 cells) should be placed on silane coated glass slides. Digestion in pepsin
      (2 mg/ml) for 30 min is adequate for DNA detection by PCR in situ hybridization
      whereas optimal protease digestion time is variable and related to formalin
      fixation time for reverse transcriptase (RT) in situ PCR. RT in situ PCR requires
      an overnight digestion with DNase. The amplifying solution should contain 4.5 mM
      MgCl2, 0.05% bovine serum albumin, and, for RNA analysis, the reporter
      nucleotide. A false positive signal would be evident with incorporation of the
      reporter nucleotide for DNA targets due to DNA repair; this can be avoided with
      frozen, fixed tissues and the hot start maneuver. Otherwise, one needs to use a
      labeled probe and a hybridization step to detect amplified DNA targets in
      paraffin embedded tissues.

PMID- 9601529
TI  - Generation of high efficiency ssDNA hybridization probes by linear polymerase
      chain reaction (LPCR).
AB  - The polymerase chain reaction (PCR) methodology can be employed to produce DNA
      hybridization probes. The major advantages of this paradigm over other techniques
      include superior specific activity of the probes, the versatility of sequence
      selection, the ability to produce short probes, and the simplicity of the
      procedure. We have further improved the efficiency of PCR probes by generating
      single stranded (ssDNA) probes that do not reanneal with themselves in solution,
      and hence, their availability for the interaction with the complementary
      sequences of the target is profoundly increased. Protocols for 32P-dCTP labeled
      and digoxigenin-dUTP labeled probes have been elaborated to maximize the
      incorporation rate of the label as well as to provide for the production of full
      length probes. The ssDNA probes may be particularly suitable for nucleic acid
      detection in tissues by in situ hybridization.

PMID- 9601530
TI  - Nucleic acid detection by in situ molecular immunogold labeling procedures.
AB  - We have recently combined immunogold labeling procedures with molecular biology
      methods to pinpoint the precise locations of nucleic acids in biological material
      at the ultrastructural level. These new immunocytological approaches involve the
      incorporation of labeled nucleotides in the nucleic acids present at the surface
      of ultrathin sections prior to immunogold labeling. The antibodies used recognize
      a nucleoside analogue (bromodeoxyuridine) or a hapten (biotin) employed to label
      nucleotides. Examples of high-resolution detection include DNA or RNA present in
      different substructures of cell nuclei, and in particular, in adenovirus-induced
      intranuclear regions of HeLa cells. In addition to being highly sensitive and
      specific, these new methods offer the possibility of studying the spatial
      distribution of nucleic acids in very well preserved, readily recognizable
      structures.

PMID- 9601531
TI  - Hydration-scanning tunneling microscopy as a reliable method for imaging
      biological specimens and hydrophilic insulators.
AB  - The recently discovered high lateral conductivity of molecularly thin adsorbed
      water films enables investigation of biological specimens, and even of surfaces
      of hydrophilic insulators by scanning tunneling microscopy (STM). Here we
      demonstrate the capabilities of this method, which we call hydration-STM (HSTM),
      with images of various specimens taken in humid atmosphere: We obtained images of
      a glass coverslip, collagen molecules, tobacco mosaic virus, lipid bilayers and
      cryosectioned bovine achilles tendon on mica. To elucidate the physical mechanism
      of this conduction phenomenon we recorded current-voltage curves on hydrated
      mica. This revealed a basically ohmic behavior of the I-V curves without a
      threshold voltage to activate the current transport and indicates that
      electrochemistry probably does not dominate the surface conductivity. We assume
      that the conduction mechanism is due to structuring of water at the surface.

PMID- 9601532
TI  - Imaging molecular structure of channels and receptors with an atomic force
      microscope.
AB  - Biological membranes contain specialized protein macromolecules such as channels,
      pumps and receptors. Physiologically, membranes and their constituent
      macromolecules are the interface surfaces toward which most of the regulatory
      biochemical and other signals are directed. Yet very little is known about these
      surfaces. The structure of biological membranes has been analyzed primarily using
      imaging techniques that are limited in their resolution of surface topology. An
      atomic force microscope (AFM) developed by Binnig, Quate and Gerber, can image
      molecular structures on specimen surfaces with subnanometer resolution, under
      diverse environmental conditions. Also, AFM can manipulate surfaces with
      molecular precision: it can nanodissect, translocate, and reorganize molecules on
      surface. The surface topology has been imaged for several hydrated channels,
      pumps and receptors which were a) present in isolated native membranes, b)
      reconstituted in artificial membrane or, c) expressed in an appropriate
      expression system. These images, at molecular resolution, reveal exciting new
      findings about their architecture. AFM induced "force dissection" reveals
      surfaces which are commonly inaccessible. In whole cell studies, in addition to
      the molecular structure of membrane receptors and channels, correlative
      electrical and biochemical activities have been examined. Such study suggests a
      "single cell" experiment where the structure-function correlation of many cloned
      channels and receptors can be understood.

PMID- 9601533
TI  - Atomic force microscopy of DNA, nucleoproteins and cellular complexes: the use of
      functionalized substrates.
AB  - Progress towards rapid and simple characterization of biomolecular samples by
      scanning probe microscopy is impeded mainly by limitations of the current
      approach to sample preparation. We are working on approaches based on chemical
      functionalization of mica. Treatment of mica with aminopropyltriethoxy silane
      (APTES) makes the surface positively charged (AP-mica) and able to hold DNA in
      place for imaging, even in water. We have shown that AP-mica is an appropriate
      substrate for numerous nucleoprotein complexes as well. The AFM images of the
      complex of DNA with RecA protein are stable and indicate a structural periodicity
      for this filament. AP-mica holds strongly such large DNA complexes as kinetoplast
      DNA (kDNA) and is an appropriate substrate for their imaging with AFM. We have
      further develop this approach for making hydrophobic substrates. Silylation of
      mica surface with hexamethyldisilazane (Me-mica) allowed us to get AFM images of
      chlorosomes, an antenna complex isolated from green photosynthetic bacteria. Me
      mica may be converted into a positively charged substrate after treatment with
      water solutions of tetraethylammonium bromide or cetyltrimethylammonium bromide.
      These activated surfaces show high activity towards binding the DNA molecules.

PMID- 9601534
TI  - Microscopic analysis of DNA and DNA-protein assembly by transmission electron
      microscopy, scanning tunneling microscopy and scanning force microscopy.
AB  - To investigate DNA and DNA-protein assembly, nucleic acids were adsorbed to
      freshly cleaved mica in the presence of magnesium ions. The efficiency of DNA
      adhesion and the distribution of the molecules on the mica surface were checked
      by transmission electron microscopy. In addition, various kinds of DNA-protein
      interactions including DNA wrapping and DNA supercoiling were analyzed using
      electron microscopy. In parallel, this Mg2+/mica method can be applied (1) to
      analyze embedded DNA by scanning tunneling microscopy, (2) to visualize freeze
      dried, metal coated DNA-protein complexes by tunneling microscopy, and (3) to
      image DNA or DNA-protein interaction in air or in liquid by scanning force
      microscopy. An advantage of such a correlative approach is that parallel imaging
      can reveal complementary information. The benefit of such a combined approach in
      analysis of protein-induced DNA bending is discussed.

PMID- 9601535
TI  - Imaging soft materials with scanning tunneling microscopy.
AB  - By modifying freeze-fracture replication, a standard electron microscopy fixation
      technique, for use with the scanning tunneling microscope (STM), a variety of
      soft, non-conductive biomaterials can be imaged at high resolution in three
      dimensions. Metal replicas make near ideal samples for STM in comparison to the
      original biological materials. Modifications include a 0.1 micron backing layer
      of silver and mounting the replicas on a fine-mesh silver filters to enhance the
      rigidity of the metal replica. This is required unless STM imaging is carried out
      in vacuum; otherwise, a liquid film of contamination physically connects the STM
      tip with the sample. This mechanical coupling leads to exaggerated height
      measurements; the enhanced rigidity of the thicker replica eliminates much of the
      height amplification. Further improvement was obtained by imaging in a dry
      nitrogen atmosphere. Calibration and reproducibility were tested with replicas of
      well characterized bilayers of cadmium arachidate on mica that provide regular
      5.5 nm steps. We have used the STM/replica technique to examine the ripple shape
      and amplitude in the P beta phase of dimyristoylphosphatidyl-choline (DMPC) in
      water. STM images were analyzed using a cross-correlation averaging program to
      eliminate the effects of noise and the finite size and shapes of the metal grains
      that make up the replica. The correlation averaging allowed us to develop a
      composite ripple profile averaged over hundreds of individual ripples and
      different samples. The STM/replica technique is sufficiently general that it can
      be used to examine a variety of hydrated lipid and protein samples at a lateral
      resolution of about 1 nm and a vertical resolution of about 0.3 nm.

PMID- 9601536
TI  - Accessing nuclear structure for field emission, in lens, scanning electron
      microscopy (FEISEM).
AB  - Scanning electron microscopy (SEM) has had a shorter time course in biology than
      conventional transmission electron microscopy (TEM) but has nevertheless produced
      a wealth of images that have significantly complemented our perception of
      biological structure and function from TEM information. By its nature, SEM is a
      surface imaging technology, and its impact at the subcellular level has been
      restricted by the considerably reduced resolution in conventional SEM in
      comparison to TEM. This restriction has been removed by the recent advent of high
      brightness sources used in lensfield emission instruments (FEISEM) which have
      produced resolution of around 1 nanometre, which is not usually a limiting figure
      for biological material. This communication reviews our findings in the use of
      FEISEM in the imaging of nuclear surfaces, then associated structures, such as
      nuclear pore complexes, and the relationships of these structures with
      cytoplasmic and nucleoplasmic elements. High resolution SEM allows the
      structurally orientated cell biologist to visualise, directly and in three
      dimensions, subcellular structure and its modulation with a view to
      understanding, its functional significance. Clearly, intracellular surfaces
      require separation from surrounding structural elements in vivo to allow surface
      imaging, and we review a combination of biochemical and mechanical isolation
      methods for nuclear surfaces.

PMID- 9601537
TI  - Problems in preparation of chromosomes for scanning electron microscopy to reveal
      morphology and to permit immunocytochemistry of sensitive antigens.
AB  - Although much information about chromosome structure and behaviour has been
      obtained using light microscopy, greater resolution is needed for a thorough
      understanding of chromosome organisation. Scanning electron microscopy (SEM) can
      provide valuable data about these three-dimensional organelles. The introduction
      of methods using osmium impregnation of methanol-acetic acid-fixed chromosome
      spreads revolutionised matters, producing life-like images of chromosomes.
      Nevertheless, it became clear that osmium impregnation introduced various
      artefacts, although the resulting images were still useful. Methanol-acetic acid
      fixed chromosomes are, in fact, flattened on the glass substratum, and the 3
      dimensional appearance obtained after osmium impregnation is the result of
      swelling during this process. At the same time, the fibrous substructure of the
      chromosomes becomes much coarser. More recently a number of alternative methods
      have become available for studying chromosomes by SEM. Isolated chromosomes, that
      have not been allowed to dry during preparation, retain a 3-dimensional
      appearance without osmium impregnation, and the same is true of methanol-acetic
      acid-fixed chromosomes that have been treated with 45% acetic acid and processed
      without drying; however, these methods do not permit the routine production of
      intact metaphase spreads. Use of cytocentrifuge preparations obviates the use of
      acetic acid fixation and osmium impregnation, produces intact metaphase spreads,
      and permits the immunocytochemical detection of antigens that are easily
      destroyed by routine fixation procedures.

PMID- 9601538
TI  - Electro-optical imaging of F-actin and endoplasmic reticulum in living and fixed
      plant cells.
AB  - Confocal and video micrographs of living and fixed alfalfa roots, onion
      epithelial and pear pollen cells illustrate the architecture of the cytoskeleton
      and endoplasmic reticulum in plant cells. Fixation of plant tissues to preserve
      cytoplasmic structure poses special problems. When possible, emphasis should be
      placed on the imaging of structures in stained living cells over time. The early
      events that occur when Nod factors or bacteria elicit nodule formation in alfalfa
      roots will illustrate several approaches to plant cell fixation, staining and
      imaging. The first observable events after Nod factor stimulation occur in root
      hairs and are changes in rates of cytoplasmic streaming, nuclear movements, and
      changes in the shape of the vacuole. Within ten minutes, the endoplasmic
      reticulum shifts position towards the tip of the root hair. For comparison, the
      endoplasmic reticulum localization in pollen tubes and onion epithelial cells
      will be illustrated. The actin cytoskeleton undergoes a series of changes over a
      twelve hour period. These changes in the cytoskeleton are spatially and
      temporally correlated with the observed growth changes of the root hairs. This
      dynamic change of the actin filament and endoplasmic reticulum and associated
      secretory vesicles in these root hairs suggests a mechanism for the observed root
      hair growth changes.

PMID- 9601540
TI  - Video rate confocal laser scanning reflection microscopy in the investigation of
      normal and neoplastic living cell dynamics.
AB  - The introduction of video rate confocal laser scanning microscopes (VRCLSM) used
      in reflection mode with high magnification, high aperture objective lenses and
      with further magnification by a zoom facility allowed the first detailed
      observations of the activity of living cytoplasm and offered a new tool for
      investigation of the structural transition from the living state to the specimen
      fixed for electron microscopy (EM). We used a Noran Odyssey VRCLSM in reflection
      (backscattered) mode. A greater degree of oversampling and more comfortable
      viewing of the liver or taped video image was achieved at zoom factor 5, giving a
      display monitor field width of 10 microns. A series of mesenchyme derived cell
      lines--from normal cells to sarcoma cells of different malignancy--was used to
      compare behaviour of the observed intracellular structures and results of
      fixation. We contrasted the dynamic behaviour of fine features in the cytoplasm
      of normal and neoplastic living cells and changes induced by various treatments.
      The tubulomembraneous 3D structure of cytoplasm in living cells is dynamic with
      motion observable at the new limits of resolution provided by VRCLSM. All
      organelles appear integrated into one functional compartment supporting the
      continuous 3D trafficking of small particles (vesicles). This integrated dynamic
      spatial network (IDSN) was found to be largest in neoplastic cells.

PMID- 9601539
TI  - Neural transplant staining with DiI and vital imaging by 2-photon laser-scanning
      microscopy.
AB  - We are developing a multielectrode silicon "neuroprobe" for maintaining a long
      term, specific, two-way electrical interface with nervous tissue. Our approach
      involves trapping a neuron (from an embryonic rat hippocampus) in a small well
      with a stimulation/recording electrode at its base. The well is covered with a
      grillwork through which the neuron's processes are allowed to grow, making
      synaptic contact with the host tissue, in our case a cultured slice from a rat
      hippocampus. Each neuroprobe can accommodate 15 neurons, one per well. As a first
      step in studying neurite outgrowth from the neuroprobe, it was necessary to
      develop new staining techniques so that neurites from the probe neurons can be
      distinguished from those belonging to the host, without interference from non
      specific background staining. We virtually eliminated background staining through
      a number of innovations involving dye solubility, cell washing, and debris
      removal. We also reduced photobleaching and phototoxicity, and enhanced imaging
      depth by using a 2-photon laser-scanning microscope. We focused on using the
      popular membrane dye, DiI, however a number of other membrane dyes were shown to
      provide clear images of neural processes using pulsed illumination at 900 nm.
      These techniques will be useful to others wishing to follow over time the growth
      of neurons in culture of after transplantation in vivo, in a non-destructive way.

PMID- 9601541
TI  - Emerging applications of fluorescence spectroscopy to cellular imaging: lifetime
      imaging, metal-ligand probes, multi-photon excitation and light quenching.
AB  - Advances in time-resolved fluorescence spectroscopy can be applied to cellular
      imaging. Fluorescence lifetime imaging microscopy (FLIM) creates image contrast
      based on the decay time of sensing probes at each point in a two-dimensional
      image. FLIM allows imaging of Ca2+ and other ions without the need for wavelength
      ratiometric probes. Ca2+ imaging can be performed by FLIM with visible wavelength
      excitation. Instrumentation for FLIM is potentially simple enough to be present
      in most research laboratories. Applications of fluorescence are often limited by
      the lack of suitable fluorophores. New, highly photostable probes allow off
      gating of the prompt autofluorescence, and measurement of rotational motion of
      large macromolecules. These luminescent metal-ligand complexes will become widely
      utilized. Modern pulse lasers allow new experiments based on non-linear
      phenomena. With picosecond and femtosecond lasers fluorophores can be excited by
      simultaneous absorption of two or three photons. Hence, Ca2+ probes, membrane
      probes, and even intrinsic protein fluorescence can be excited with red or near
      infrared wavelengths, without ultraviolet lasers or optics. Finally, light itself
      can be used to control the excited state population. By using light pulses whose
      wavelength overlaps the emission spectrum of a fluorophore one can modify the
      excited state population and orientation. This use of non-absorbed light to
      modify emission can have wide reaching applications in cellular imaging.

PMID- 9601542
TI  - Comparative scanning, transmission and atomic force microscopy of the
      microtubular cytoskeleton in fenestrated liver endothelial cells.
AB  - Endothelial fenestrae control the exchange of fluids, solutes and particles
      between the sinusoidal lumen and the microvillous surface of the parenchymal
      cells. Fenestrae have a critical dimension in the order of 150-200 nm, making it
      necessary to use microscopes with a resolution better than the light microscope.
      Comparative whole-mount preparations of isolated, purified and cultured rat liver
      sinusoidal endothelial cells (LEC) were studied by scanning electron microscopy
      (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM).
      Examination of detergent-extracted LEC by SEM and TEM shows an integral
      cytoskeleton: sieve plates are delineated by a sieve plate-associated
      cytoskeleton ring and fenestrae by a fenestrae-associated cytoskeleton ring. By
      using microtubule altering agents we could demonstrate: (1) the architectural
      role of microtubules in arranging fenestrae, (2) the existence of a population of
      microtubules resistant against low temperature and colchicine, (3) the ability of
      LEC to shift the microtubule assembly-disassembly steady state under various
      conditions, (4) and the necessity of an intact microtubular cytoskeleton to
      support the increase in the number of fenestrae after cytochalasin B.
      Topographical examinations of AFM images revealed that sieve plates are
      delineated by elevated borders, probably projections of the underlying tubular
      cytoskeleton.

PMID- 9601543
TI  - Correlated confocal and intermediate voltage electron microscopy imaging of the
      same cells using sequential fluorescence labeling, fixation, and critical point
      dehydration.
AB  - Confocal laser scanning microscopy (CLSM) and intermediate voltage transmission
      electron microscopy (IVEM) each has its own particular advantages. CLSM can
      examine living cells, but is particularly useful when applied to cells that have
      been lightly fixed, permeabilized, and stained with fluorescent-labeled
      antibodies for localization of specific molecular species at the resolution of
      the light microscope while still in the hydrated state. IVEM provides much higher
      resolution images, but requires more drastic preparation procedures, including
      dehydration. This paper presents methods for combining these complementary
      approaches to examine exactly the same cells sequentially by CLSM and IVEM. Cells
      are grown in culture on sterile formvar films spread over gold index grids on
      cover glasses, which are mounted on larger cover glasses or microscope slides
      with spacers to prevent compression of the cells. Light and epifluorescence
      microscopy, and CLSM are performed concentrating on cells in grid openings. Then
      the grids are fixed with aldehydes followed by OsO4, dehydrated and critical
      point dried (CPD) from liquid CO2. Immediately following CPD, the grids are ready
      for examination in the IVEM. Low magnification (300-600x) survey images allow
      correlation of the IVEM images with the light microscopic images. In higher power
      images, structures that are fluorescent labeled can be related to corresponding
      regions in the IVEM images.

PMID- 9601544
TI  - Pre-embedding staining of single muscle fibers for light and electron microscopy
      studies of subcellular organization.
AB  - Skeletal muscle fibers are large, multinucleated cells which pose a challenge to
      the morphologist. In the course of studies of the distribution of the glucose
      transporter GLUT4, in muscle, we have compared different preparative procedures,
      for both light (LM) and electron microscopy (EM) immunocytochemistry. Here we
      show that pre-embedding staining of single teased fibers, or of single
      enzymatically dissociated fibers, has several advantages over the use of sections
      for observing discrete patterns that extend over long distances in the cells. We
      report on an optimization study carried out to establish fixation and
      permeabilization conditions for EM immunogold labeling of the fibers. We find
      that a simple fixation with depolymerized paraformaldehyde alone, followed by
      permeabilization with 0.01% saponin, offers the best compromise between the
      conflicting demands of unhindered tissue penetration and morphology preservation.

PMID- 9601545
TI  - Multiple labeling in electron microscopy: its application in cardiovascular
      research.
AB  - The heart is a muscular pump kept together by a network of extracellular matrix
      components. An increase in collagens, as in chronic congestive heart failure
      (CHF), is thought to have a negative effect on cardiac compliance and, thus, on
      the clinical condition. Conventional electron microscopy allows for the study of
      cellular and extracellular components and scanning electron microscopy (SEM) can
      put these structures in three-dimensional perspective. However, in order to study
      extracellular matrix components in relation to cells, immunoelectron microscopy
      is superior. We have used this technique in our studies on heart failure. Heart
      specimens were fixed in 4% paraformaldehyde and 0.1% glutaraldehyde in sodium
      cacodylate buffer, dehydrated by the method of progressive lowering of
      temperature and embedded in LR Gold plastic. Immunolabeling could be achieved
      with different sized gold-conjugated secondary antibodies or protein-A gold
      conjugates. Depending on the objective, ultra small gold (USG) conjugates or a
      regular probe size can be used. Labeling efficiency could be increased by
      bridging antibodies. The double and triple staining procedures were based on
      single staining methods using one- and two-face labeling. The choice of
      antibodies and gold conjugates depended on the objectives. Immunoelectron
      microscopy, using multiple labeling, allowed a detailed study of the organization
      of the extracellular matrix and its relationship with cardiac myocytes. This may
      prove to be a useful tool for the study of chronic heart failure.

PMID- 9601546
TI  - Covalent labeling of proteins with fluorescent compounds for imaging
      applications.
AB  - The labeling of proteins with fluorescent compounds for microscopy has allowed a
      greater understanding of biological processes. The preparation of fluorescent
      proteins is the first step in development of their use in microscopy. Methods are
      described to label and characterize a protein as an example of the general
      approach for other proteins. Skeletal muscle alpha-actinin was labeled with
      either fluorescein-5-maleimide or 5-iodoaceamidofluorescein and the reaction
      characterized. The maleimide reaction was much more rapid and efficient than the
      iodoacetamide reaction giving a coupling efficiency of 65% under the given ration
      conditions. The fluorescein-5-maleimide alpha-actinin was functionally
      characterized and there was essentially no influence on the fluorescein label on
      the F-actin binding properties of alpha-actinin. The fluorescein alpha-actinin
      was also shown to specifically bind to the Z-line of isolated myofibrils. A
      general outline and discussion are presented on how to label and characterize
      proteins for use in microscopy.

PMID- 9601548
TI  - Freeze-dried human leukocytes stabilized with uranyl acetate during low
      temperature embedding or with OsO4 vapor after embedding.
AB  - Two new simple stabilization procedures for freeze-dried biological material are
      introduced which are compatible with low temperature embedding (LTE) in Lowicryl.
      The first method uses a Lowicryl K11M/HM20 mixture supplemented with 0.3% uranyl
      acetate for LTE. For the second method polymerized Lowicryl blocks containing the
      freeze-dried material are exposed to OsO4 vapor which penetrates into the
      Lowicryl block and stabilizes the embedded specimen. The quality of structural
      preservation is demonstrated with human leukocytes.

PMID- 9601547
TI  - Cytoskeleton architecture of C6 rat glioma cell subclones whole mount electron
      microscopy and immunogold labeling.
AB  - Whole mount electron microscopy of extracted cells combined with immunogold
      labeling techniques can be used to characterize the cytoskeletal architecture of
      cultured cells. As shown with subclones of the C6 rat glioma cell line, heavy
      metal shadowing was suitable for getting basic information concerning the
      arrangement of the various filament types within the networks. Pure carbon
      shadowing combined with immunogold double labeling proved to be optimal to
      identify linkages between filaments, to localize filament associated proteins and
      to follow the arrangement of filaments in dense arrays such as lamellipodiae and
      cell margins. Thin connecting filaments which interact with actin as well as with
      vimentin filaments and can be labeled with antibodies to the intermediate
      filament associated protein plectin may play a major role in the structural
      organization of the cytoskeleton of these cells.

PMID- 9601549
TI  - Labeling with nanogold and undecagold: techniques and results.
AB  - A significant new development in gold labeling for microscopy has been achieved
      through the use of gold cluster compounds that are covalently attached to
      antibodies or other probe molecules. These unique gold probes are smaller than
      most colloidal gold conjugates and exhibit improved penetration into tissues,
      higher labeling densities, and allow many new probes to be made with peptides,
      nucleic acids, lipids, drugs, and other molecules. A new fluorescent-gold
      conjugate is useful for examining localization by fluorescence microscopy, then
      visualizing the same label at the ultrastructural level in the electron
      microscope.

PMID- 9601550
TI  - Immunocytochemistry by electron spectroscopic imaging using well defined
      boronated monovalent antibody fragments.
AB  - Contributing to the rapidly developing field of immunoelectron microscopy a new
      kind of markers has been created. The element boron, incorporated as very stable
      carborane clusters into different kinds of peptides, served as a marker
      detectable by electron spectroscopic imaging (ESI)--an electron microscopic
      technique with high-resolution potential. Covalently linked immunoreagents
      conspicuous by the small size of both antigen recognizing part and marker moiety
      are accessible by using peptide concepts for label construction and their
      conjugation with Fab' fragments. Due to a specific labeling of the free thiol
      groups of the Fab' fragments, the antigen binding capacity was not affected by
      the attachment of the markers and the resulting immunoprobes exhibited an
      elongated shape with the antigen combining site and the label located at opposite
      ends. The labeling densities observed with these reagents were found to be
      significantly higher than those obtained by using conventional colloidal gold
      methods. Combined with digital image processing and analysis systems, boron-based
      ESI proved to be a powerful approach in ultrastructural immunocytochemistry
      employing pre- and post-embedding methods.

PMID- 9601551
TI  - Specimen preparation of the human cerebellar cortex for scanning electron
      microscopy using a t-butyl alcohol freeze-drying device.
AB  - A freeze-drying device was applied to t-butyl alcohol substituted nerve cells,
      fibers and synaptic terminals. Ten percent formalin-fixed human cerebellar cortex
      specimens were postfixed in 2.5% glutaraldehyde in 0.1 M cacodylate buffer
      solution and were rinsed three times in 5% sucrose solution in the same buffer.
      After the postfixed specimens were dehydrated using a graded series of ethanols
      and then transferred into a graded series of t-butyl alcohols (freezing point
      25.4 degrees C), the t-butyl alcohol substituted specimens were freeze-dried at
      15 degrees C and at high vacuum (5 x 10(-2) Torr). The freeze-dried specimens
      were sputter coated with gold. Scanning electron microscopy revealed synaptic
      terminals on the surfaces of a Golgi cell and a small flat polygonal cell. Rough
      somatic surfaces of granule cells were also observed.

PMID- 9601552
TI  - X-ray microscopy: preparations for studies of frozen hydrated specimens.
AB  - X-ray microscopes provide higher resolution than visible light microscopes. Wet,
      biological materials with a water thickness of up to about 10 microns can be
      imaged with good contrast using soft X-rays with wavelengths between the oxygen
      and carbon absorption edges (at 24 and 43 A). The Stony Brook group has developed
      and operates a scanning transmission X-ray microscope (STXM) at the National
      Synchrotron Light Source (NSLS) at Brookhaven National Laboratory. The microscope
      is used for imaging with a current resolution of 50 nm, and for elemental and
      chemical state mapping. Radiation damage imposes a significant limitation upon
      high resolution X-ray microscopy of room temperature wet specimens. Experience
      from electron microscopy suggests that cryo techniques allow vitrified specimens
      to be imaged repeatedly. This is due to the increased radiation stability of
      biological specimens in the frozen hydrated state. Better radiation stability has
      been shown recently with a cryo transmission X-ray microscope developed by the
      University of Gottingen, operating at the BESSY storage ring in Berlin, Germany.
      At Stony Brook, we are developing a cryo scanning transmission X-ray microscope
      (CryoSTXM) to carry out imaging and spectro-microscopy experiments on frozen
      hydrated specimens. This article will give an outlook onto the research projects
      that we plan to perform using the CryoSTXM.

PMID- 9601553
TI  - In vitro systems and cultured cells as specimens for X-ray microanalysis.
AB  - In vitro systems and cultured cells are recognized as useful systems in many
      areas of biomedical research, including X-ray microanalysis. To be reliable, in
      an vitro system should have an elemental composition close to that of the tissue
      in situ, react in the same way to stimuli, and retain the in situ regulation of
      ion transport. In the present paper, four of the most commonly used in vitro
      systems will be reviewed: incubated tissue slices (liver and pancreas), isolated
      glands (submandibular gland acini, sweat glands), primary cell cultures (sweat
      glands, endometrium), and cell lines (the colon cancer cell line T84,
      immortalized sweat gland cells). Incubation of tissue slices of liver in Krebs
      Ringers buffer caused a significant increase in Na and Cl and a decrease in K.
      Initially, these changes were also observed in the pancreas, but here the values
      gradually returned to normal. Isolated submandibular gland acini, and isolated
      sweat gland ducts and coils react in a similar way to stimulation as their in
      situ counterparts. In primary cultures of coil cells, however, part of the cell
      population acquires different ion transport characteristics. Technically simplest
      is the use of cell lines originating from cancer cells (e.g., the T84 cell line)
      and immortalized cell lines. X-ray microanalysis not only confirms data on ion
      transport obtained with other techniques, but adds the possibility to investigate
      the presence of subpopulations within a culture.

PMID- 9601554
TI  - Aspects of cryofixation and cryosectioning for the observation of bulk biological
      samples in the hydrated state by cryoelectron microscopy.
AB  - Cryoelectron microscopy allows the observation of hydrated samples at high
      spatial resolution, and it would be of great interest in biology to apply this
      method to cells and tissues. However, because of technical problems, the cryo
      observation of frozen hydrated ultrathin sections of bulk material has not become
      an established method. The major limitations are due to the difficulty of
      achieving the vitrification of such material, and the structural deformation
      caused by ultrathin sectioning: 1. The vitrification of cells in a physiological
      environment requires high-pressure freezing. However, new results suggest that
      the pressure may alter the ultrastructure of the sample. 2. Cryosectioning
      compresses structures in the cutting direction about 40%. This deformation does
      not necessarily destroy the character of macromolecular assemblies, but since it
      depends on the properties of the material, internal standards cannot be used to
      correct for the deformation of all the structures in a cell.

PMID- 9601555
TI  - Advanced instrumentation and methodology related to cryoultramicrotomy: a review.
AB  - This review is concerned with the considerable progress in the field of cryo
      ultramicrotomy (cryofixation, cryosectioning, investigation and analysis of
      cryosections) during recent years. This progress includes both more efficient
      instrumentation and methodology. The article is mainly directed to the
      investigation and analysis of frozen-hydrated sections in the low dose cryo
      transmission electron microscopy (TEM) and cryo-energy filtered TEM (EFTEM). A
      general survey is followed by an evaluation of the different relevant procedures.
      Both cryo-ultramicrotomy for macromolecular cytochemistry (Tokuyasu technique)
      and cryo-ultramicrotomy for element analysis are only shortly mentioned without
      discussion of the chemical and analytical approach. Because of lack of first hand
      experience, cryo-sectioning for X-ray microanalysis in the frozen-hydrated state
      according to Hall and Gupta is not included into this review. The methods and
      instruments required for ultrathin sectioning at low temperatures are described
      and discussed in detail. This concerns the preceding cryofixation, the
      cryosectioning itself with special emphasis to the required stability and
      precision of the cryo-ultramicrotome, the characteristics of the knives, the
      charging phenomena due to sectioning and the subsequent TEM investigation
      including EFTEM with electron spectroscopic imaging (ESI) and the available
      accessories for digital low dose registration of signals.

PMID- 9601557
TI  - 44th Annual conference of the American Society for Artificial Internal Organs.
      New York, New York, USA. April 23-25, 1998. Abstracts.

PMID- 9601558
TI  - XIXth Congress of the European Society of Cardiology together with the 32nd
      Annual General meeting of the Association of European Paediatric Cardiologists.
      Stockholm, Sweden, August 24-28, 1997. Abstracts.

PMID- 9601556
TI  - International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports
      Medicine 1st Biennial Congress. Buenos Aires, Argentina, May 11-16, 1997.
      Abstract.

PMID- 9601559
TI  - XIIIth Congress of the European Association of Urology. Barcelona, Spain, March
      21-25, 1998. Abstracts.

PMID- 9601561
TI  - Index of titles and authors 1969-1996.

PMID- 9601560
TI  - 42nd Symposium of the German Society of Endocrinology, Freiburg, Germany, March 4
      7, 1998. Abstracts.

PMID- 9601562
TI  - The Proceedings of the 74th annual meeting of the Physiological Society of Japan.
      Hamamatsu, Japan, March 26-28, 1997. Abstracts.

PMID- 9601564
TI  - The Physiological Society proceedings of the scientific meeting held at
      University of Cambridge, 15-17 December 1997.

PMID- 9601563
TI  - 23rd Annual meeting of the American Society of Andrology. Long Beach, California,
      USA. March 26-29, 1998. Abstracts.

PMID- 9601565
TI  - 6th Annual meeting of the Israel Society for Neurosciences. Eilat, Israel,
      December 7-10, 1997. Abstracts.

PMID- 9601566
TI  - Oncology Nursing Society 23rd annual congress. San Francisco, California, USA.
      May 7-10, 1998. Abstracts.

PMID- 9601567
TI  - Oncology Nursing Society directory.

PMID- 9601568
TI  - The American Pediatric Society and The Society for Pediatric Research. New
      Orleans, Louisiana, USA. May 1-5, 1998. Abstracts.

PMID- 9601569
TI  - 18th Annual Conference on Peritoneal Dialysis, 4th International Symposium on
      Home Hemodialysis, 9th Annual Symposium on Pediatric Peritoneal Dialysis.
      Nashville, Tennessee, USA. February 23-25, 1998. Abstracts.

PMID- 9601571
TI  - Cumulative index volumes 1-199.

PMID- 9601570
TI  - 1998 AAHPERD National Convention. Reno, Nevada, USA. April 1998. Abstracts.

PMID- 9601572
TI  - Contribution of myocyte apoptosis to myocardial infarction?

PMID- 9601573
TI  - Cardiomyocyte apoptosis in acute and chronic conditions.
AB  - Myocytes can die by necrosis or by apoptosis and the characteristics of both
      kinds of cell death are so typical that a differentiation can be made by
      histological and molecular-biological methods using electron microscopy, dUTP
      labeling with fluorescence or peroxidase staining (TUNEL) and the DNA laddering
      method. However, the problem of quantification of apoptotic cells has not been
      completely solved because of lack of standardization as well as uncritical use
      and interpretation of the TUNEL method. Equally, quantification of apoptotic
      cells is not optimal until now because of three reasons: methodological
      (overinterpretation of results, no differentiation between myocytes and non
      myocytes), experimental (global or regional acute ischemia, chronic conditions
      such as heart failure or hibernating myocardium), and interpretation (unknown
      time period for the completion of apoptosis). This problem is reflected in the
      large differences in incidence of apoptosis reported. Our own data show that in
      dog myocardium made globally ischemic for 90 min, 8% of the myocytes showed a
      positive staining for apoptosis (TUNEL method) after 6 h of reperfusion. Despite
      these results the question of reperfusion injury and the influence of apoptosis
      still remains open, because it can not be excluded until now that the apoptotic
      process is initiated during the ischemic period. Studies in hibernating
      myocardium and chronic heart failure show a similar situation, because of a wide
      variation of numbers of apoptotic cells and the limited possibility to
      investigate human tissue. There is no doubt that apoptosis plays an important
      role in chronic pathophysiological situations such as heart failure and
      hibernating myocardium but the importance of apoptosis in the acute situation of
      ischemia/reperfusion still has to be clarified.

PMID- 9601574
TI  - Accelerated apoptosis in reperfused myocardium: friend of foe?

PMID- 9601575
TI  - Apoptosis is prevented by administration of superoxide dismutase in dogs with
      reperfused myocardial infarction.

PMID- 9601576
TI  - Tumor necrosis factor-alpha is expressed by monocytes/macrophages following
      cardiac microembolization and is antagonized by cyclosporine.
AB  - The time course of expression of TNF-alpha in myocardial wound healing following
      ischemic injury was investigated in the porcine heart. Microembolization was used
      to induce focal ischemia and necrosis in hearts of 39 adult pigs. The animals
      were sacrificed after 3, 6, 12, 24 h, 3 and 7 days, and after 4 weeks, and the
      myocardial tissue was studied by immunofluorescence using specific antibodies.
      TNF-alpha containing cells were identified as monocytes/macrophages by double
      staining with a muramidase antibody. Monocytes/macrophages were the only source
      of TNF-alpha. Microembolization caused multiple necrotic foci with loss of
      myocytes in the left ventricular myocardium. These foci contained numerous
      monocytes/macrophages and showed an inflammatory reaction typical of wound
      healing followed by replacement with scar tissue. The number of TNF-alpha
      positive cells increased after 24 h, peaked between 3-7 days and slowly decreased
      thereafter. Expression of TNF-alpha in monocytes/macrophages was significantly
      reduced after pretreatment of pigs with cyclosporine or dexamethasone. It is
      concluded that 1.) in myocardial tissue monocytes/macrophages are the only cell
      type expressing TNF-alpha, 2.) TNF-alpha is involved in wound healing after
      ischemia, and 3.) synthesis of TNF-alpha and inflammatory angiogenesis can be
      inhibited be treatment with either cyclosporine or dexamethasone.

PMID- 9601577
TI  - Vascular remodeling in balloon injured rabbit iliac arteries.
AB  - To characterize long-term vascular remodeling associated with neointimal
      formation in vivo, we established a model of balloon injury in normal chow fed
      rabbits. The iliac artery was injured by denudation using a 2F embolectomy
      catheter. Injured vessels were removed after perfusion fixation (90 mm Hg) in
      situ at 2, 4, 6, and 12 weeks post-injury; control vessels were obtained from 2-
      and 12-week age-matched, uninjured animals. Intimal growth was observed in all
      animals post-injury. Intimal area averaged 0.13 +/- 0.02 mm2 2 weeks post-injury
      and continued to increase at 4 and 6 weeks post-injury; +38% and +77% relative to
      the 2-week time point, respectively. Medical areas were similar among the 2-, 4-,
      and 6-week injury groups and the 2- and 12-week control groups. From 6 to 12
      weeks post-injury, both intimal and medial areas decreased significantly (30% and
      34%, respectively); while lumen area increased 53% from 4 to 12 weeks and overall
      vessel size (area enclosed by the external elastic lamina) remained the same.
      These data demonstrate that intimal and medial thinning contribute to long term
      maintenance of lumen area in response to neointimal formation.

PMID- 9601578
TI  - Cardiac and coronary vascular effects of chronically administered estrogen in the
      dog.
AB  - The acute administration of conjugated equine estrogen (CEE) to dogs
      significantly attenuated the severity and incidence of ventricular arrhythmias
      during ischemia and reperfusion. We hypothesized that one of the cardioprotective
      mechanisms of estrogen might be the ability to maintain electrical stability of
      the heart during ischemia. The current study was conducted to determine the
      effect of chronic administration of estrogen, simulating hormone replacement
      therapy, on the ventricular arrhythmias of ischemia and reperfusion. Chronically
      treated (100 micrograms/kg/week CEE, or vehicle) male beagles were anesthetized
      and subjected to regional ischemia (20 min) and reperfusion. Although there was a
      trend towards a lower incidence of arrhythmias during ischemia in estrogen
      treated dogs, values did not achieve significance at P < 0.05. Baseline coronary
      vascular resistance was significantly higher in estrogen-treated dogs (2.3 vs 1.5
      mmHg/ml/min/100 g, P < 0.05) indicating an increase in vasomotor tone. There was
      also an increase in the time it took hyperemic coronary blood flow to reach a
      peak value upon reperfusion (71 sec in estrogen-treated dogs vs 12 sec in vehicle
      treated dogs, P < 0.05). This slower reflow is consistent with increased coronary
      vascular resistance upon reflow in estrogen-treated dogs. We conclude that the
      chronic administration of CEE to male dogs increased coronary vascular tone, and
      impaired the rate of reperfusion, but did not decrease the incidence of
      ventricular arrhythmias caused by ischemia.

PMID- 9601579
TI  - Temporal changes in the subcellular distribution of protein kinase C in rabbit
      heart during global ischemia.
AB  - Our recent studies utilizing an in vivo regional ischemia model revealed no
      changes in the subcellular distribution of protein kinase C (PKC) in dog and
      rabbit hearts after repeated 5 min episodes of preconditioning
      ischemia/reperfusion. However, 10 min of sustained ischemia resulted in an
      increase in PKC activity in the membrane fraction. These findings indicate that
      prolonged ischemia may cause changes in the subcellular distribution of PKC.
      However, the detailed time course of these changes during sustained severe
      ischemia is poorly resolved. Thus, our objective was to study temporal changes in
      PKC distribution in the cytosolic, nuclear, and membrane fractions isolated from
      globally ischemic rabbit heart. Hearts were removed under deep anesthesia, placed
      into normal saline at 37 degrees C, and repeatedly sampled from apex to base at
      baseline, 2, 5, and 10 min into global ischemia, with matched samples obtained in
      every heart. PKC activity was increased at 2 min into global ischemia in both the
      nuclear fraction (1069 +/- 75 vs. 893 +/- 49 pmol/min/g at baseline; p = 0.05)
      and the membrane fraction (1374 +/- 95 vs 1187 +/- 59 pmol/min/g at baseline; p <
      0.05) with persistent translocation observed at 5 and 10 min into the protocol.
      Thus, direct biochemical determination of PKC activity in the isolated rabbit
      heart revealed increased activity in the nuclear and the membrane fractions as
      early as 2 min into global ischemia.

PMID- 9601580
TI  - Clofilium in the isolated perfused rabbit heart: a new model to study
      proarrhythmia induced by class III antiarrhythmic drugs.
AB  - OBJECTIVE: The clinical usefulness of class III antiarrhythmic drugs for the
      treatment of tachyarrhythmias is limited by their potential proarrhythmic
      effects, mainly torsades-depointes (TdP). The goal of this experimental study was
      to develop an isolated whole-heart model exhibiting typical characteristics of
      class III drug-induced ventricular arrhythmias. METHODS: Isolated rabbit hearts
      were perfused with a Krebs-Henseleit buffer containing 10 microM clofilium and
      then exposed to a modified Krebs-Henseleit buffer with 2.0 mM K+ and 0.5 mM Mg2+.
      Hearts subjected to either clofilium alone or modified buffer alone were used as
      controls. RESULTS: Under clofilium the QT interval increased from 187 +/- 16 to
      282 +/- 33 ms. Within 8 to 25 s after the change of the perfusate, ventricular
      arrhythmias developed in all hearts associated with a further QT prolongation to
      380 +/- 73 ms when the first ventricular extrasystole occurred. Simultaneously,
      the monophasic action potential durations increased relatively more during late
      repolarization; from 99 +/- 21 to 110 +/- 25 ms (+11%) at 50% repolarization,
      from 143 +/- 24 to 178 +/- 40 ms (+24%) at 70%, and from 200 +/- 30 to 275 +/- 53
      ms (+38%) at 90%. The predominant rhythm was polymorphic with either two
      alternating or multiple QRS morphologies exhibiting the characteristic features
      of torsades-depointes. All control hearts stayed in normal sinus rhythm.
      CONCLUSION: Under the conditions selected, the isolated perfused rabbit heart
      represents a useful experimental approach to study the proarrhythmic effects of
      class III agents. This model provides a convenient way to manipulate the ionic
      and pharmacologic milieu in a preparation conserving the functional anatomy of
      the whole organ without interference by cardiovascular reflexes. It might be
      useful for analyzing the conditions favoring and preventing drug-induced torsades
      depointes.

PMID- 9601581
TI  - Collateral response to activation of potassium channels in vivo.
AB  - Activation of ATP-sensitive K+ channels is involved in the coronary vascular
      response to decreases in perfusion pressure and ischemia. Since activation of ATP
      sensitive K+ channels in collateral vessels may be important in determining flow
      to collateral-dependent myocardium, the ability of collaterals to respond to
      activation of the channel was tested. In the beating heart of dogs, we compared
      responses of non-collaterals less than 100 microns in diameter to collaterals of
      similar size using computer-controlled stroboscopic epi-illumination of the left
      ventricle coupled to a microscope-video system. Aprikalim, a selective activator
      of ATP-sensitive K+ channels (0.1-10 microM) produced similar dose-dependent
      dilation of non-collaterals and collaterals. Relaxation was decreased by
      inhibition of ATP-sensitive K+ channels with glibenclamide, but not by inhibition
      of nitric oxide synthase with nitro-L-arginine. Bradykinin (10-100 microM)
      produced similar dilation of non-collaterals and collaterals which was decreased
      by nitro-L-arginine but not glibenclamide. Thus, in microvascular collaterals,
      relaxation to both nitric oxide and activation of ATP-sensitive K+ channels is
      similar to non-collaterals.

PMID- 9601582
TI  - The information technology revolution and burns.

PMID- 9601583
TI  - Long-term functional sequelae after paediatric burns.
AB  - Ninety-one patients with at least 5 per cent (median 10 per cent, maximum 50 per
      cent) total body surface area (TBSA) burns were clinically re-examined on average
      17.3 yr after primary injury. The patients had sustained mostly superficial
      dermal scalds. The most common long-term functional sequelae were impaired
      tanning (n = 67; 77.7 per cent), diminished tactile sensibility (n = 50; 56.2 per
      cent) and increased reddening (n = 14; 15.6 per cent) either in the sun or the
      Finnish sauna. Five patients (6.3 per cent) had limited joint mobility and one
      patient experienced constrictive scars on her trunk during pregnancy. Scar
      appearance was significantly associated with impaired tactile sense (chi 2 =
      11.87, DF = 2, p < 0.01; Spearman's R = 0.27, p = 0.03). Surprisingly, better
      scar appearance showed more disturbed touch sensation. The primary operative
      treatment (early excision and split skin grafting) was not associated with
      diminished sense of touch (chi 2 = 1.24, DF = 1, p = 0.27). Neither were scar
      appearance and poor tanning significantly associated (chi 2 = 1.63, DF = 1, p =
      0.4). Only three patients suffered no functional detriments. In this series the
      harmful functional consequences were generally slight. The aetiological
      background (scalds) and the relatively small, superficially burned skin area
      probably explains the good late outcome. However, since nearly every burn-injured
      child will have some signs of the injury in adulthood, children present a
      constant challenge in the effort for better burn care and prevention.

PMID- 9601584
TI  - Alternative delivery of keratinocytes using a polyurethane membrane and the
      implications for its use in the treatment of full-thickness burn injury.
AB  - The Epicel ASAProgram service generates autologous keratinocyte grafts used for
      the closure of full-thickness wounds in moderately and severely burned patients.
      The manufacturing process used to generate Epicel service autografts (ESA) is
      based upon the keratinocyte co-culture technique described by Rheinwald and Green
      which employs murine Swiss 3T3/J2 fibroblasts as feeder cells. Recently, a
      technique has been described that employs a polyurethane wound dressing,
      HydroDerm (HD, Innovative Technologies, Ltd), as a delivery vehicle for cultured
      keratinocytes intended for autologous grafting. We have examined the practical
      feasibility of this technique and report on testing the ability of HD to support
      keratinocyte growth and epithelium formation in vitro, at the air-liquid
      interface (ALI), and in vivo, after grafting to full-thickness wounds created on
      the backs of athymic (Swiss Nu/Nu) mice. The results demonstrate that
      keratinocytes grow on the HD dressing in Gibco SFM at a rate that is
      approximately 15 per cent of that observed when cells are cultivated on tissue
      culture (TC) plastic using standard techniques, yet the cells retain their
      proliferative capacity and form an epithelium in vitro when cultivated at the ALI
      on a dermal substrate. Keratinocyte-seeded HD membranes were also transferred to
      full-thickness wounds in athymic mice. Animals grafted with cells seeded to HD
      developed human epithelium, as revealed by species-specific detection of
      involucrin and evolved a normal attachment to the wound substratum, as
      demonstrated through the expression of dermally opposed laminin and alpha 6 beta
      4 integrin. The ability of keratinocytes to maintain proliferative potential
      after seeding onto HD and their ability to form a properly oriented epithelium in
      vitro and in vivo suggests that this wound dressing may be useful as a vehicle
      for autologous keratinocyte grafting and help to provide earlier epithelial
      coverage to the burned patient. However, because of the slow proliferation rate
      of keratinocytes on HydroDerm, timely graft delivery would be best achieved by
      combining cell expansion via the Rheinwald and Green culture system, followed by
      the seeding of cells onto HydroDerm in a reduced calcium medium for subsequent
      autologous grafting.

PMID- 9601585
TI  - Skin banking in the UK: the need for proper organization.
AB  - Skin banking was set up in Sheffield in 1991 to provide a readily available
      source of allograft material to be used both for research purposes and also as a
      means of providing immediate wound cover for major burns patients. Once skin was
      available, however, clinical demand for it both within and outside Sheffield,
      outstripped the resources to run the bank. Logistical difficulties were
      encountered in the day to day running of the bank. These revolved around shortage
      of staff available for harvesting, the relative lack of public awareness of skin
      donation, shortage of banked skin as the bank became more widely known and lack
      of space and finance to expand. The decision was made to transfer the now
      established skin bank to the National Blood Service where it now operates with
      staff and resources dedicated specifically to this purpose. Experience leads to
      the suggestion that there is a clinical need for allograft skin in the UK which
      is not being met at the present time. There is a need for dedicated properly
      resourced skin banks and for the Department of Health to introduce regulation,
      monitoring and inspection of skin bank facilities in order to safeguard
      standards.

PMID- 9601586
TI  - The European Directory of Burns Research.
AB  - The European Directory of Burns Research is a database of research activity in
      Europe. This ongoing database, established under the auspices of the Research
      Committee of the European Burns Association (EBA), provides basic information on
      research studies in progress or completed. The first issue, for the period
      1995/1996, present information received after return of 118 questionnaires from
      researchers working in 27 countries in Europe and its close neighbours. This is
      not a large number of responses and may reflect problems with access to groups
      working in burns, but ignorant of the request for information on research
      activities. The aim is to maintain and update the database annually through
      distribution and return of a simple questionnaire. Information will be available
      to EBA members on request but the accuracy and detail of the database will
      ultimately be influenced by the co-operation of the burns research community.

PMID- 9601587
TI  - Is there an evidence-based practice for burns?
AB  - Doubts and questions about clinical decision making need to be answered. Evidence
      based medicine aims to provide answers by systematically finding information from
      the vast assortment of research papers in the literature and bringing it together
      to use in everyday practice and in the best interests of the patient. Although
      clinical (and experimental) studies have a variety of methodologies, ranging from
      small descriptive studies to large multi-centre trials all are vital in
      describing or posing questions about the array of responses elicited when human
      beings are burned and subsequently treated. When it comes to treatment (be it a
      drug, a dressing, an enteral feed for example) the 'gold standard' for
      establishing whether it is effective is the randomized controlled trial (RCT).
      Using contemporary information retrieval systems and the numerous establishments
      set up to help track down information of research in medicine relevant to health
      practice and policy the numbers of RCTs, systematic reviews and meta-analyses of
      burn care have been established. Whilst the numbers of RCTs are increasing there
      is little evidence that burn care is an evidence-based practice.

PMID- 9601588
TI  - The usefulness of combined high-frequency percussive ventilation during acute
      respiratory failure after smoke inhalation.
AB  - Inhalation injury and bacterial pneumonia represent some of the most important
      causes of mortality in burn patients. We describe 11 severely burned patients
      with acute respiratory failure due to inhalation injury who did not respond
      adequately to conventional respiratory support. High-frequency percussive
      ventilation (HFPV) is a recent ventilatory mode, which combines the advantages of
      conventional ventilation with some of those of high-frequency ventilation. Seven
      patients developed pulmonary infection during the acute phase; one patient died
      of multiple organ failure on day 25. All the other patients survived; two
      developed bronchiolitis obliterans symptoms before discharge. No side-effects
      were noted and haemodynamic tolerance of HFPV was excellent. Our findings suggest
      that HFPV can improve pulmonary function and gas exchange in these catastrophic
      pulmonary failures following inhalation injury.

PMID- 9601590
TI  - Autologous skin banking.
AB  - Small amounts of excess autograft are commonly harvested during burn procedures,
      and typically these are discarded. However, the resources of a local skin bank
      may be used to preserve this tissue for a later autologous use. This has been a
      routine practice in our institution and we feel that it has impacted favorably on
      patient care. In this paper we report 42 consecutive applications of autologous
      frozen skin and illustrate the technique with a case report.

PMID- 9601589
TI  - Effect of cutaneous burn injury and resuscitation on the cerebral circulation in
      an ovine model.
AB  - The aim of our study was to evaluate the effects of a large cutaneous burn injury
      on the cerebral circulation. Anesthetized sheep (n = 8) were prepared with
      vascular catheters, a urinary catheter and a Richmond bolt for intracranial
      pressure monitoring. A scald injury was inflicted on 70 percent of total body
      surface area with hot water. Resuscitation was started 30 min after scald with
      Ringer's lactate to restore and maintain baseline oxygen delivery. Resuscitation
      maintained blood pressure, cardiac output and urine output at normal levels.
      Brain blood flow was measured with colored microspheres. During resuscitation
      intracranial pressure rose slowly from 10.6 +/- 1.5 to 17.0 +/- 4.0 mmHg (P <
      0.05) and cerebral perfusion pressure was reduced from 86.4 +/- 6.8 to 64.1 +/-
      2.8 mmHg (P < 0.05). During early resuscitation cerebrovascular resistance
      declined to maintain brain blood flow and oxygen delivery at baseline or better.
      After 6 h, mean cerebrovascular resistance was inappropriately increased during a
      period of reduced cerebral perfusion pressure which resulted in brain blood flow
      reductions of half the baseline levels. These data suggest that autoregulation
      maintains brain blood flow immediately after burn shock and early resuscitation,
      but the autoregulation may be less effective as burn resuscitation proceeds.

PMID- 9601591
TI  - Use of Biobrane in pediatric scald burns--experience in 106 children.
AB  - This report describes 141 scalded children admitted from January 1993 to June
      1995. The mean age of patients was 2 yr 11 months. The average burn size was 11.4
      percent TBSA. The male to female ratio was 1.6:1 (87:54). One hundred and six of
      the children were initially diagnosed as suffering from superficial or medium
      partial-thickness burns. After proper evaluation and resuscitation, all of them
      received immediate debridement and Biobrane coverage. This biosynthetic dressing
      was fixed with adhesive tape and compressive dressing. No splints were used. Pain
      tolerance was good and these children were able to resume their daily activities
      as early as possible. If vital signs were stable and Biobrane adherence occurred,
      the patients were discharged. The dressings were easily changed on an out-patient
      basis; therefore, the hospital stay and ultimate cost of burn care both
      decreased. This experience confirmed that Biobrane is quite suitable for
      consideration in treating pediatric scalds. Accurate diagnosis of depth is very
      important. The best results can be obtained only on superficial partial-thickness
      burns. A high wound infection rate occurred in the medium partial-thickness burn
      wounds (7.8 vs. 62.1 percent).

PMID- 9601592
TI  - The safety of topical anaesthetic and analgesic agents in a gel when used to
      provide pain relief at split skin donor sites.
AB  - Post operative pain from split skin donor sites is a recognised problem. This
      study was carried out to assess the safety of a 'depot' preparation of
      bupivacaine and ketoprofen when applied to denuded dermis of a split donor site.
      Two groups of six patients each received either bupivacaine gel (2.5 mg/ml) or
      ketoprofen gel (1.6 mg/ml). One patient from each group was excluded as protocol
      was not followed. The mean surface area for bupivacaine was 106 cm2 (range 64
      160) and the mean for ketoprofen was 130 cm2 (range 64-180). Blood samples were
      obtained before application and at 10, 20, 30, 60, 120, 240 and 480 min after
      application. Serum levels were assayed using Gas Liquid Chromatography and High
      Pressure Liquid Chromatography. Bupivacaine levels peaked at 120 min, mean level
      obtained was 0.07 microgram/ml (range 0.03-0.1). Ketoprofen levels also peaked at
      120 min and the mean level obtained was 0.20 microgram/ml (range 0.12-0.27). The
      reported toxic serum level for bupivacaine was 4 micrograms/ml and for ketoprofen
      is 1128 micrograms/ml. In conclusion, these preparations, when applied to denuded
      dermis of a split skin donor site, are unlikely to result in toxic levels.

PMID- 9601593
TI  - Major burns in Cape Town: a modified burns score for patient triage.
AB  - Major burns equal to, or greater than, 30 per cent total body surface area (TBSA)
      constitute 23 per cent of the admissions to the adult burns unit in Cape Town. A
      retrospective review over a 28-month period identified 87 cases of major burns.
      This paper summarizes the epidemiology and mortality amongst this patient group
      over this period. Demand for treatment can exceed bed availability in the unit.
      The difficult issue, this raises, of patient triage in relation to the relatively
      limited resources is addressed and a simple modified burns score proposed for
      this unit. The effect this score would have in optimizing the use of our
      resources is demonstrated.

PMID- 9601594
TI  - Cicatricial, postburn ectropion and exposure keratitis.
AB  - Exposure keratitis can lead to infectious keratitis, corneal perforation,
      blindness and disfigurement. Chronic exposure of the cornea can occur following
      facial burns that cause eyelid ectropion. This complication can be difficult to
      diagnose in the unconscious patient. Five patients have undergone lid ectropion
      release to 11 eyelids in the early postburn period over the past 5 years. One
      patient required repeat release. Full-thickness skin grafts were used for the
      lower eyelid and no graft failure occurred. Operations were performed between 30
      50 days postburn. Plastic wrap was used in one patient as a temporary dressing to
      maintain corneal hydration until surgery could be performed. All the patients
      were noted to have exposure keratitis on ophthalmological review. Patients most
      at risk are those with large area burns that include the face, who require
      prolonged intensive care support. It is important to look out for the development
      of eyelid ectropion, which should be corrected when first diagnosed to prevent
      disabling, sight-threatening eye injury.

PMID- 9601595
TI  - Sarcoma developing in a burn scar: case report and review of the literature.
AB  - The development of malignancy in burn scars is a well known entity. However, burn
      scar sarcomas are rarely seen. This report presents the first case of a
      leiomyosarcoma arising in a burn scar of scalp in the English literature.

PMID- 9601596
TI  - Successful cure of an extensive burn injury complicated with mucor wound sepsis.
AB  - Mucormycosis is an opportunistic infection occurring in the severely
      immunocompromised patient. A case of mucormycosis occurring in a patient who
      sustained an 85 per cent TBSA burn injury is reported. Diagnosis and management
      is reported in the paper.

PMID- 9601598
TI  - The revolutionary dual cyclone vacuum cleaner--a new cause of digital friction
      burns in children.
AB  - Household domestic appliances are often sources of potential hazard for young
      children. This case report illustrates this with reference to a revolutionary
      dual cyclone vacuum cleaner causing a full thickness burn in a young child.

PMID- 9601597
TI  - Severe heat stroke associated with high plasma levels of plasminogen activator
      inhibitor 1.
AB  - In a 38-year-old man, severe heat stroke caused disseminated intravascular
      coagulation (DIC) associated with significantly elevated plasma plasminogen
      activator inhibitor 1 levels. Investigation of the effects of hyperthermia on
      coagulation and fibrinolysis showed, in apparent conflict with previous reports,
      a time lag between the initial hypercoagulable and hyperfibrinolytic response
      (within 24 hr) and hypofibrinolysis shown by a disproportionate increase of PAI-1
      (after 24 h), which possibly occurs in correspondence with the recovery of
      vascular endothelial integrity. The patient was discharged without sequelae
      although computed tomography (CT) scans indicated the likelihood of venous
      infarction or posterior inferior cerebellar artery area infarction secondary to
      DIC.

PMID- 9601599
TI  - Burnaid.

PMID- 9601600
TI  - Dangers of the intake of psoralens and subsequent UV exposure producing
      significant burns.

PMID- 9601601
TI  - Hot water injury to a child's airway which spared the mouth and tongue.

PMID- 9601602
TI  - Current evidence suggests independent regulation of nuclear calcium.
AB  - We review and present current evidence supporting independent regulation of
      nuclear Ca2+ ([Ca2+]n). The nucleus and nuclear envelope contain proteins to both
      regulate and respond to changes in [Ca2+]n. However, this does not prove that
      [Ca2+]n is independently regulated from cytosolic Ca2+ ([Ca2+]c). Studies using
      fluorescent dyes suggested that changes in [Ca2+]n differed in magnitude from
      changes in [Ca2+]c. These studies have been criticised as the nuclear environment
      alters the fluorescent characteristics of these dyes. We have evaluated this
      question with aequorin targeted to the nucleus and cytoplasm and shown that the
      characteristics of the indicators are not altered in their respective
      environments. We have demonstrated that different stimuli induce changes in
      [Ca2+]n and [Ca2+]c that vary both temporally and in magnitude. The nucleus
      appeared to be shielded from increases in [Ca2+]c, either through a mechanism
      involving the nuclear envelope or by cytosolic buffering of localised increases
      in Ca2+. In addition, agonist stimulation resulted in an increase in [Ca2+]n,
      consistent with release from the perinuclear Ca2+ store. There was a stimulus
      dependence of the relation between [Ca2+]n and [Ca2+]c suggesting differential
      regulation of [Ca2+]n. These results have important implications for the role of
      Ca2+ as a specific regulator of nuclear events through Ca2+ binding proteins. In
      addition, they highlight the advantages of using targeted aequorin in intact
      cells to monitor changes in organelle [Ca2+].

PMID- 9601603
TI  - The calcium store in the nuclear envelope.
AB  - The nuclear envelope has a relatively small volume, but is connected up to the
      vastly larger endoplasmic reticulum. The Ca2+ concentration in the lumen of the
      interconnected nuclear envelope and endoplasmic reticulum network is in the
      resting state maintained at a level of more than 100 microM. There are specific
      Ca2+ release channels present in the inner nuclear membrane that can be activated
      by inositol trisphosphate or cADP ribose. The system, therefore, allows selective
      release of Ca2+ into the nucleoplasm which could be important for the control of
      specific types of gene expression.

PMID- 9601604
TI  - Calcium regulation of nuclear pore permeability.
AB  - The nuclear envelope is an integral part of the structural framework of the
      nucleus, and is involved in organizing intranuclear events. It serves as a
      selective barrier, actively transporting proteins required for normal nuclear
      function and exporting RNA. The movement of molecules across the nuclear envelope
      is critical for cellular homeostasis, and it allows cells to respond to external
      events. The only known pathway for direct communication between the cytoplasm and
      the nucleoplasm of a cell is through the nuclear pore complex. In the past
      decade, rapid advances have been made in elucidating the structure and function
      of the nuclear pore complex. Yet, researchers are just beginning to identify some
      of the regulatory mechanisms controlling transport through the pore complex. The
      nucleus is surrounded by a Ca2+ storage compartment, which sequesters and
      releases Ca2+ in response to intracellular second messengers, Recent evidence
      suggests that the nuclear Ca2+ store may indirectly regulate passive diffusion
      through the nuclear pore complex. The evidence for Ca2+ regulation of the nuclear
      pore complex will be discussed, along with the introduction of the simplest,
      testable model to describe the observations.

PMID- 9601605
TI  - The role of Ca2+/calmodulin-dependent protein kinases within the nucleus.
AB  - Stimulation of cells by Ca(2+)-linked signaling agents increases Ca2+ levels
      within both the cell cytosol and nucleus. The multifunctional Ca2+/calmodulin
      dependent protein kinase (CaM kinase) family, consisting of CaM kinases I, II and
      IV, have all been detected within the nucleus and each may serve as a mediator of
      nuclear Ca2+ signals. Certain isoforms of the large multimeric CaM kinase II are
      targeted to the nucleus as a result of an alternatively spliced nuclear
      localization signal. By contrast, CaM kinases I and IV are monomeric and likely
      gain nuclear access by passive diffusion through nuclear pores. These kinases
      have activation properties which may allow them to discriminate between Ca2+
      signals which differ in their spike frequency, amplitude and duration. In
      addition, these kinases have the ability to control gene expression through the
      phosphorylation of key regulatory sites on nuclear transcription factors. CaM
      kinases may thus serve to decode Ca2+ signals to the nucleus in order to produce
      a multitude of cellular responses including control of cell cycle, apoptosis and
      synaptic efficacy.

PMID- 9601606
TI  - New nuclear functions for calmodulin.
AB  - The data reported here summarize a series of results which reveal new functions
      for nuclear calmodulin (CaM). The addition of CaM inhibitors to cultures of
      proliferating NRK cells blocked the activity of the cyclin-dependent protein
      kinases 4 (cdk4) and 2 (cdk2), which are enzymes implicated in the progression of
      G1 and in the onset of DNA replication, respectively. CaM modulates the activity
      of cdk4 by regulating the nuclear location of both cdk4 and cyclin D, its
      associated regulatory subunit. By using CaM-affinity chromatography, we have
      recently identified two new nuclear CaM-binding proteins: (i) the protein La/SSB,
      which is an autoantigen implicated in several autoimmune diseases such as lupus
      erythematosus and Sjogren's syndrome (since La/SSB participates in the process of
      transcription mediated by RNA polymerase III, CaM could be involved in the
      regulation of this process); and (ii) the protein SAP145, a member of the
      spliceosome-associated proteins (SAPs) which is a subunit of the splicing factor
      SF3(b). This finding suggests the involvement of CaM in pre-mRNA splicing.
      Finally, a screening for new CaM-binding proteins in the fission yeast performed
      by using the phage display analysis, revealed that several nucleolar-ribosomal
      proteins associate to CaM, suggesting that CaM modulates ribosomal assembly
      and/or function.

PMID- 9601607
TI  - Calcium, protease action, and the regulation of the cell cycle.
AB  - Proteolysis is a key event in the control of the cell cycle. Most of the proteins
      which are degraded at specific cycle points, e.g. cyclins A, B, and E, are
      substrates of the ubiquitin/proteasome pathway. The Ca2+ dependent neutral
      protease calpain also cleaves cell cycle proteins, among them cyclin D1 and the c
      mos proto-oncogene product which is a component of the CSF. The proteasome
      itself, however, may be under Ca2+ control through the binding of Ca2+ to its 29
      kDa regulatory subunit. Calpain undergoes relocation among cell compartments
      during the various steps of the mitotic and meitotic cycles. It promotes the
      initiation and the progression of mitosis when injected into the perinuclear
      space of synchronized PtK1 cells, and the resumption of meiosis when directly
      injected into the nuclei of prophase-arrested starfish oocytes. Apart from the
      proteins mentioned above, most of the substrates of calpain which become cleaved
      during mitosis and meiosis are still unknown. Microtubule-associated proteins are
      likely candidates.

PMID- 9601608
TI  - Mechanisms controlling gene expression by nuclear calcium signals.
AB  - Nuclear calcium is an important regulator of gene expression following membrane
      depolarisation of electrically excitable cells. Here we describe nuclear calcium
      transients in hippocampal neurons following activation of calcium influx through
      L-type voltage-sensitive calcium channels and N-methyl-D-aspartate (NMDA)
      receptors, as well as following calcium release from intracellular caffeine
      sensitive stores. Increases in nuclear calcium activate gene transcription by a
      mechanism that is distinct from gene regulation by cytoplasmic calcium signals
      and involves the cAMP response element (CRE) and the CRE binding protein, CREB.
      The nuclear calcium/calmodulin dependent (CaM) protein kinase IV, which is
      expressed in cultured hippocampal neurons and in the mouse pituitary cell line
      AtT20, may function as a mediator of nuclear calcium-induced transcription.

PMID- 9601609
TI  - Calcium regulation of basic helix-loop-helix transcription factors.
AB  - The basic helix-loop-helix (bHLH) family of transcription factors is essential
      for numerous developmental and growth control processes. The regulation of bHLH
      proteins occurs at many levels, including tissue specific expression,
      differential oligomerization and DNA binding specificities, interaction with
      negatively acting HLH proteins and post-translational modifications. This review
      focuses on what is emerging as another level of bHLH protein regulation, calcium
      regulation through interaction with Ca2+ loaded calmodulin and S-100 proteins.
      The mechanism and implications of these Ca2+ regulated interactions are
      discussed.

PMID- 9601610
TI  - The role of calcium in activity-dependent neuronal gene regulation.
AB  - Synaptic transmission is a key signaling event, whereby an action potential
      induced release of chemical neurotransmitters again generates a positive or
      negative electrical activity via opening of postsynaptic channels. Thereafter,
      information spreads through space, from the postsynaptic membranes to the
      dendrites, to the soma, to the nucleus, to the presynaptic terminals and, in some
      cases, back to the originally stimulated synapses. Furthermore, information is
      also often converted in time, either by shifting the phase of electrical activity
      during the integration of EPSPs and IPSPs into the generation of an action
      potential, or by triggering a long-lasting cascade of enzymatic or protein
      protein interaction-mediated events in the cytoplasm and in the nucleus. Recent
      studies of the signaling from the synapse to the nucleus now allow us to consider
      how various patterns of synaptic activity could couple with activation of
      specific nuclear transcription factors and thus regulate neuronal gene
      expression. The critical importance of Ca(2+)-dependent signaling processes in
      such regulatory events will be discussed below.

PMID- 9601611
TI  - TPEN, a Zn2+/Fe2+ chelator with low affinity for Ca2+, inhibits lamin assembly,
      destabilizes nuclear architecture and may independently protect nuclei from
      apoptosis in vitro.
AB  - We used Xenopus egg extracts to examine the effects of TPEN, a chelator with
      strong affinities for Zn2+, Fe2+, and Mn2+, on nuclear assembly in vitro. At
      concentrations above 1 mM, TPEN blocked the assembly of the nuclear lamina and
      produced nuclei that were profoundly sensitive to stress-induced balloon-like
      'shedding' of nuclear membranes away from chromatin-associated membranes. TPEN
      arrested nuclei were also defective for DNA replication, which could be explained
      as secondary to the lack of a lamina. Imaging of TPEN-arrested nuclei by field
      emission in-lens scanning electron microscopy (FEISEM) revealed clustered,
      structurally-perturbed nuclear pore complexes. TPEN-arrested nuclei were
      defective in the accumulation of fluorescent karyophilic proteins. All detectable
      effects caused by TPEN were downstream of the effects of BAPTA, a Ca2+/Zn2+
      chelator that blocks pore complex assembly at two distinct early stages.
      Surprisingly, TPEN-arrested nuclei, but not control nuclei, remained active for
      replication in apoptotic extracts, as assayed by [32P]-dCTP incorporation into
      high molecular weight DNA, suggesting that TPEN blocks a metal-binding protein(s)
      required for nuclear destruction during programmed cell death.

PMID- 9601612
TI  - Calcium, free radicals and excitotoxins in neuronal apoptosis.
AB  - Apoptosis is an active process of cell destruction, characterized by cell
      shrinkage, chromatin aggregation with extensive genomic fragmentation, and
      nuclear pyknosis. In contrast, necrosis is characterized by passive cell
      swelling, intense mitochondrial damage with rapid energy loss, and generalized
      disruption of internal homeostasis. This swiftly leads to membrane lysis, release
      of intracellular constituents that evoke a local inflammatory reaction, edema,
      and injury to the surrounding tissue. In collaboration, our two research
      laboratories have been defining excitotoxic signals that lead to apoptosis versus
      necrosis via, among other pathways, Ca2+ signaling mechanisms; this is the
      subject of this brief review.

PMID- 9601613
TI  - The role of calcium in apoptosis.
AB  - One general signalling mechanism used to transfer the information delivered by
      agonists into appropriate intracellular compartments involves the rapid
      redistribution of ionised calcium throughout the cell, which results in transient
      elevations of the cytosolic free Ca2+ concentration. Various physiological
      stimuli increase [Ca2+]i transiently and, thereby, induce cellular responses.
      However, under pathological conditions, changes of [Ca2+]i are generally more
      pronounced and sustained. Marked elevations of [Ca2+]i activate hydrolytic
      enzymes, lead to exaggerated energy expenditure, impair energy production,
      initiate cytoskeletal degradation, and ultimately result in cell death. Such
      Ca(2+)-induced cytotoxicity may play a major role in several diseases, including
      neuropathological conditions such as chronic neurodegenerative diseases and acute
      neuronal losses (e.g. in stroke).

PMID- 9601614
TI  - Lithium vs placebo in cluster headache.

PMID- 9601615
TI  - Regional cerebral blood flow and oxygen metabolism during migraine with and
      without aura.

PMID- 9601617
TI  - Neurogenic vs vascular mechanisms of sumatriptan and ergot alkaloids in migraine.

PMID- 9601618
TI  - Flumazenil-responsive stupor.

PMID- 9601619
TI  - Guidelines for the management of headache. Danish Neurological Society and the
      Danish Headache Society.

PMID- 9601620
TI  - Altered allelic distributions of the serotonin transporter gene in migraine
      without aura and migraine with aura.
AB  - Allelic variation of the human serotonin transporter gene (HSERT), a highly
      plausible candidate gene for susceptibility to migraine, was investigated in 266
      individuals with migraine, including 173 having migraine without aura (MO), 94
      having migraine with aura (MA), 18 with co-occurrence of MO and MA, plus 133
      unaffected controls. The distribution of a polymorphism with different forms of a
      variable tandem number repeat (VNTR) in intron 2 were compared. The MO group had
      an over-representation of genotypes with two twelve repeat alleles (STin2.12) and
      a reduction of genotypes containing one ten repeat (STin2.10) compared to
      controls. The MA group showed a similar pattern, but also a trend towards an
      increase in genotypes containing the nine repeat allele of the VNTR (STin2.9).
      Genotypes containing this allele were found in 6.4% of the MA group compared to
      2.3% of controls. The group with co-occurrence of MO and MA had a significantly
      different pattern of overall allele frequency distribution from controls,
      reflecting a reduction in genotypes containing the STin2.10 allele and a shift
      both to STin2.9 carriers and to STin2.12 homozygosity. These results support the
      view that susceptibility to MO and MA has a genetic component, that these
      disorders are distinct, and that genetic susceptibility may in some cases be
      associated with a locus at or near the serotonin transporter gene.

PMID- 9601621
TI  - Nitric oxide synthase inhibition: a new principle in the treatment of migraine
      attacks.
AB  - Glyceryl trinitrate, an exogenous nitric oxide (NO) donor, and histamine, which
      causes NO formation in vascular endothelium, have been shown to trigger migraine
      attacks. However, it remains uncertain whether NO is involved in the subsequent
      phase of migraine attacks. To answer this question we studied the effect of L
      NGmethylarginine hydrochloride (546C88), a NO-synthase inhibitor, on spontaneous
      migraine attacks. In a double-blind study design, 18 patients with migraine
      without aura randomly received 546C88 (6 mg/kg) or placebo (5% dextrose) i.v.
      given over 15 min for a single migraine attack (546C88:placebo, 15:3).
      Furthermore, 11 placebo-treated patients from previous double-blind trials with
      almost identical design were added to the placebo group in the statistical
      evaluation. Two hours after the infusion, 10 of 15 L-NGmethylarginine
      hydrochloride-treated patients experienced headache relief compared to 2 of 14
      placebo-treated patients (p = 0.01). Symptoms such as phono- and photophobia were
      also significantly improved. A similar trend for nausea was not significant. We
      conclude that NO may be involved in the pain mechanisms throughout the course of
      spontaneous migraine attacks.

PMID- 9601622
TI  - Tolerability and efficacy of naratriptan tablets with long-term treatment (6
      months). Naratriptan Long-term Study Group.
AB  - This open-label study was conducted to examine the long-term tolerability and
      efficacy of the novel 5HT1 agonist naratriptan tablets 2.5 mg used to treat all
      migraine attacks for 6 months. Patients could reduce the dose to 1 mg in the
      event of intolerable adverse events. The results demonstrate that the majority
      (median 83%) of attacks treated with naratriptan tablets 2.5 mg were not
      associated with an adverse event. Among attacks treated with naratriptan tablets
      2.5 mg (+ optional 2.5 mg for headache recurrence), the most frequently reported
      adverse event was nausea (4% of attacks after a single naratriptan dose). Both
      the overall incidence of adverse events and the incidences of specific adverse
      events were no higher during months 4-6 of treatment compared with months 1-3.
      Only 5 of 414 patients elected to reduce their naratriptan dose to 1 mg. Headache
      relief 4 h postdose was reported in a mean of 68% of 6770 moderate or severe
      migraine attacks treated with naratriptan tablets 2.5 mg. The median number of
      naratriptan tablets used per attack was 1.0 (mean 1.25); patients treated only a
      median 7% of attacks (mean 13%) with a 2nd naratriptan tablet for headache
      recurrence. Patients rated naratriptan tablets as good or excellent in 61% of
      7566 treated attacks. In summary, the data from this study demonstrate that
      naratriptan tablets 2.5 mg were very well tolerated and effective for the acute
      treatment of migraine for 6 months in a situation closely resembling actual
      clinical use.

PMID- 9601623
TI  - Ketoprofen (25 mg) in the symptomatic treatment of episodic tension-type
      headache: double-blind placebo-controlled comparison with acetaminophen (1000
      mg).
AB  - Therapies in current use for episodic tension-type headache (ETTH) are often
      unsatisfactory. Few trials have been conducted to demonstrate efficacy of any of
      them. This multicenter placebo-controlled randomized parallel-groups study
      compared the analgesic efficacy of single oral doses of ketoprofen 25 mg and
      acetaminophen 1000 mg as outpatient treatment of 1 attack of ETTH. Efficacy was
      assessed by patients as pain relief on a diary-entered 7-point categorical scale.
      A total of 457 patients treated 348 attacks, 330 of which were evaluable. There
      were no serious adverse events (AEs); gastrointestinal AEs were most common on
      all treatments. Total relief from pain after 2 h was recorded by 16% of patients
      on placebo, 28% on ketoprofen, and 22% on acetaminophen. Worthwhile effect or
      total relief (all other responses were regarded as treatment failures) were
      recorded by 36% on placebo, 70% on ketoprofen (p < 0.001), 61% on acetaminophen
      (p < 0.001). The difference between ketoprofen and acetaminophen was not
      significant (p = 0.24). Various secondary efficacy measures confirmed superiority
      of both active treatments over placebo, with some trends for slightly better
      outcome on ketoprofen that on acetaminophen. This study demonstrates that
      ketoprofen is an effective alternative to standard therapy in ETTH.

PMID- 9601624
TI  - Reliability of an illness severity measure for headache in a population sample of
      migraine sufferers.
AB  - OBJECTIVES: To examine the reliability and related measurement properties of an
      illness severity measure for headache derived from responses to a 16-item self
      administered questionnaire, the Headache Impact Questionnaire (HImQ), and to
      determine if there is support for combining measures of pain and disability into
      a single scaled measure of severity. METHODS: A population-based sample of
      migraine headache sufferers completed the HImQ twice, an average of 38 days
      apart. The HImQ included questions about number of headaches in the last 3
      months, headache duration, last headache, pain intensity (two questions), need
      for bedrest (two questions), disability in specific domains of activity (seven
      questions about interference with ability to work, do household chores, and
      engage in non-work activity), and symptoms (two questions). RESULTS: Test-retest
      correlations of individual questions ranged from 0.65 to 0.93. In principal
      components analysis, a single factor with significant loading emerged. One
      measure of pain intensity (average pain score from 0 to 10) and items related to
      disability (i.e., missed days due to headache, and reduced effectiveness because
      of headache) in defined activity domains (work for pay, housework, nonwork
      activities) had the greatest weights on this single factor, supporting prior work
      on combining measures of pain and disability into a single scale. The HImQ score
      was derived as the sum of average pain intensity and total lost time in each of
      the three domains of activity, expressed as lost days. The latter was derived as
      the sum of actual missed days in each activity domain and reduced effectiveness
      day equivalents in each activity with a headache. The test-retest correlation was
      0.77 for all eligible subjects and 0.85 when one influential outlier was removed.
      Cronbach's alpha was 0.83. CONCLUSIONS: The HImQ score, based on eight items, is
      a highly reliable and internally consistent measure of headache severity.

PMID- 9601626
TI  - An interregional comparative study of headache clinic populations.
AB  - We present a comparative study between headache clinic populations from 2
      inherently different regions of the United States. Using standardized methods, 1
      of us (JFR) prospectively evaluated 578 new patients attending the headache
      clinic at the University of California in San Diego. In a similar manner, we
      subsequently evaluated 115 new patients presenting to the headache clinic at the
      University of South Alabama in Mobile, Alabama. We found few differences between
      the 2 populations. These differences more likely reflect regional variations in
      healthcare delivery or methodologic artifact than intrinsic dissimilarities.

PMID- 9601625
TI  - Noncompliance may render migraine prophylaxis useless, but once-daily regimens
      are better.
AB  - Medicines work better if taken, which must be true of migraine prophylaxis. There
      is evidence that compliance with regular medication can be badly deficient. To
      assess how serious the problem might be in routine migraine management, we
      undertook a covert observational 2-month survey in a specialist headache clinic
      using objective measures of compliance. Subjects were 38 patients needing
      prophylaxis with medication prescribed once (od), twice (bd), or three times
      daily (tds). Medication was dispensed, unknown to them, in Medication Event
      Monitoring Systems (MEMS) to record openings in real time. Number, timing, and
      pattern of actual openings were compared with what was expected. Compliance rates
      averaged 66%, although returned pill counts indicated 91%. A substantial and
      significant difference was shown between od and bd or tds regimens. Measures of
      dosing interval--used-on-schedule rate and therapeutic coverage--averaged between
      44% and 71%. Once-daily treatment was associated with a used-on-schedule rate
      more than double those of multiple daily dosing, but still only 66%. We conclude
      that routine use of drug prophylaxis in migraine may be so seriously undermined
      by poor compliance that it has little chance of efficacy. Returned-pill counting
      is inadequate for compliance assessment.

PMID- 9601627
TI  - Subdural hematoma following disappearance of orthostatic headache and pressure
      normalization in two patients with spontaneous intracranial hypotension.

PMID- 9601628
TI  - The right to a fair trial.

PMID- 9601629
TI  - Svante Paabo: pushing ancient DNA to the limit.

PMID- 9601630
TI  - Protein NMR spectroscopy.

PMID- 9601631
TI  - Developmental neurobiology: notch is tops in the developing brain.
AB  - Signalling through the cell-surface receptor molecule Notch may regulate
      oligodendrocyte differentiation, and consequently help determine the timing, and
      perhaps the pattern, of myelination in the developing vertebrate central nervous
      system.

PMID- 9601632
TI  - Cytoskeletal proteins: the evolution of cell division.
AB  - The prokaryotic cell division protein FtsZ and eukaryotic tubulin have been shown
      to have very similar structures and are most likely homologs. The evolutionary
      transition from FtsZ to tubulin could provide a window into the transition from
      prokaryotic cells to eukaryotic cells.

PMID- 9601633
TI  - Visual development: making maps in the dark.

PMID- 9601634
TI  - Malaria: dissecting chloroquine resistance.
AB  - The malaria parasite's development of resistance to the drug chloroquine is a
      major threat to world health. A protein likely to be involved in chloroquine
      resistance has recently been identified; this discovery is important, but raises
      as many questions as it answers.

PMID- 9601635
TI  - Synaptic plasticity: going through phases with LTP.
AB  - Early and late expressing components of synaptic plasticity may underlie the
      temporal phases of behavioral memory. New studies argue that a balance between
      kinase and phosphatase activity regulates the transition between different phases
      of synaptic plasticity and memory.

PMID- 9601636
TI  - Leukemogenesis: small differences in Myb have large effects.
AB  - The avian retroviruses E26 and AMV carry mutated versions of the gene encoding
      the cellular transcription factor c-Myb. Surprisingly, these two mutant forms of
      Myb differ in the subsets of myeloid cells that they transform, the target genes
      that they activate, and the way in which they are regulated.

PMID- 9601637
TI  - Muscle development: a transcriptional pathway in myogenesis.
AB  - Recent studies have substantially advanced our understanding of the
      transcriptional program regulating development of the different muscle types in
      Drosophila. For body wall muscle, a pathway can now be drawn that links the
      transcription factor Dorsal, inherited from the egg, with the differentiated
      muscle protein tropomyosin.

PMID- 9601638
TI  - Defective negative regulation of antigen receptor signaling in Lyn-deficient B
      lymphocytes.
AB  - BACKGROUND: To elucidate the role of the Src family kinase Lyn in B cell receptor
      (BCR) signaling, we and others previously generated lyn-/- mice and analyzed
      their B cell responses. Although the initiation of BCR signaling in lyn-/- B
      cells is delayed, BCR-induced ERK2 activation and proliferation are enhanced. As
      the co-receptors Fc gamma RIIb1 and CD22 have been shown to be negative
      regulators of BCR signaling, we have now examined their functional roles in lyn-/
      B cells. RESULTS: B cells from lyn-/- mice have increased expression of the
      protein product of the early response gene egr-1, enhanced activation of Jun N
      terminal kinase (JNK), and elevated calcium responses upon BCR cross-linking.
      Tyrosine phosphorylation of Fc gamma RIIb1 in lyn-/- B cells was reduced but
      negative regulation of the BCR signal by Fc gamma RIIb1 was only modestly
      impaired. In contrast, tyrosine phosphorylation of CD22 was greatly decreased in
      lyn-/- B cells, correlating with the inability of CD22 to downregulate the BCR
      induced calcium response in these cells. Surprisingly, CD22 remains capable of
      regulating the ERK2 and JNK pathways in lyn-/- B cells, which may relate to the
      small residual increase in BCR-induced CD22 phosphorylation. CONCLUSIONS: BCR
      signal initiation and negative regulation by Fc gamma RIIb1 is not critically
      dependent on Lyn. In contrast, Lyn plays a particularly important role in the
      tyrosine phosphorylation of CD22 and in the consequent inhibition of BCR-induced
      calcium influx. The net result of the Lyn deficiency in B cells is
      hyperresponsiveness to antigen stimulation, which may explain the autoimmunity
      observed in lyn-/- mice.

PMID- 9601639
TI  - Vav is a regulator of cytoskeletal reorganization mediated by the T-cell
      receptor.
AB  - BACKGROUND: Vav is a guanine-nucleotide exchange factor for the Rho-like small
      GTPases RhoA, Rac1 and Cdc42, which regulate cytoskeletal reorganization and
      activation of stress-activated protein kinases (SAPK/JNKs). Vav is expressed in
      hematopoietic cells and is phosphorylated in T and B cells following activation
      of various growth factor or antigen receptors. Vav interacts with several
      signaling molecules in T cells, but the functional relevance of these
      interactions is established only for Slp76: they cooperate to induce activity of
      the transcription factor NF-AT and interleukin-2 expression. We have investigated
      the role of Vav in T cells by generating vav-/- mice. RESULTS: Mice deficient for
      vav were viable and healthy, but had impaired T-cell development. In vav-/- T
      cells, in response to activation of the T-cell receptor (TCR), cell cycle
      progression, induction of NF-ATc1 activity, downregulation of the cell-cycle
      inhibitor p27Kip1, interleukin-2 production, actin polymerization and the
      clustering of TCRs into patches and caps--a cytoskeletal reorganization process-
      were defective. TCR-mediated activation of mitogen-activated protein kinase and
      SAPK/JNK was unaffected. Ca2+ mobilization was impaired in vav-/- thymocytes and
      T cells. In wild-type cells, Vav constitutively associated with the cytoskeletal
      membrane anchors talin and vinculin. In the absence of Vav, phosphorylation of
      Slp76, Slp76-talin interactions, and recruitment of the actin cytoskeleton to the
      CD3 zeta chain of the TCR co-receptor were impaired. CONCLUSIONS: Vav is a
      crucial regulator of TCR-mediated Ca2+ flux, cytoskeletal reorganization and TCR
      clustering, and these are required for T-cell maturation, interleukin-2
      production and cell cycle progression.

PMID- 9601640
TI  - Defects in actin-cap formation in Vav-deficient mice implicate an actin
      requirement for lymphocyte signal transduction.
AB  - BACKGROUND: Antigen-receptor interactions on lymphocytes result in local
      clustering of actin, receptors and signaling molecules into an asymmetric
      membrane structure termed a cap. Although actin polymerization is known to be
      required, the mechanisms underlying cap formation are unclear. We have studied
      the events underlying cap formation using mice bearing a null mutation in vav
      (vav-/-), a gene that encodes a guanine-nucleotide exchange factor for the GTPase
      Rac. RESULTS: Lymphocytes from vav-/- mice failed to form T-cell receptor caps
      following activation and had a defective actin cytoskeleton. The vav-/- T cells
      were deficient in interleukin-2 (IL-2) production and proliferation, and the peak
      of Ca2+ mobilization was reduced although of normal duration. Activation of Jun N
      terminal kinase or stress-activated kinase (JNK or SAPK) and mitogen-activated
      protein kinase (MAPK) and the induction of the transcription factor NF-ATc1 and
      egr-1 genes was normal. Despite the reduced Ca2+ mobilization, translocation of
      cytoplasmic NF-ATc to the nucleus was normal, reflecting that the lower levels of
      Ca2+ in vav-/- cells were still sufficient to activate calcineurin. Treatment of
      lymphocytes with cytochalasin D, which blocks actin polymerization, inhibited cap
      formation and produced defects in signaling and IL-2 transcriptional induction in
      response to antigen-receptor signaling that were nearly identical to those seen
      in vav-/- cells. In transfection studies, either constitutively active Vav or Rac
      could complement constitutively active calcineurin to activate NF-AT-dependent
      transcription. CONCLUSIONS: These results indicate that Vav is required for cap
      formation in lymphocytes. Furthermore, the correlation between cap formation, IL
      2 production and proliferation supports the hypothesis that an actin-dependent
      pathway is a source of specialized growth regulatory signals.

PMID- 9601641
TI  - Downregulation of beta-catenin by human Axin and its association with the APC
      tumor suppressor, beta-catenin and GSK3 beta.
AB  - BACKGROUND: Inactivation of the adenomatous polyposis coli (APC) tumor suppressor
      protein is responsible for both inherited and sporadic forms of colon cancer.
      Growth control by APC may relate to its ability to downregulate beta-catenin post
      translationally. In cancer, mutations in APC ablate its ability to regulate beta
      catenin, and mutations in beta-catenin prevent its downregulation by wild-type
      APC. Moreover, signaling by the protein product of the wnt-1 proto-oncogene
      upregulates beta-catenin and promotes tumorigenesis in mice. In a Xenopus
      developmental system, Wnt-1 signaling was inhibited by Axin, the product of the
      murine fused gene. This suggests a possible link between Axin, the Wnt-1
      signaling components beta-catenin and glycogen synthase kinase 3 beta (GSK3
      beta), and APC. RESULTS: Human Axin (hAxin) binds directly to beta-catenin, GSK3
      beta, and APC in vitro, and the endogenous proteins are found in a complex in
      cells. Binding sites for Axin were mapped to a region of APC that is typically
      deleted due to cancer-associated mutations in the APC gene. Overexpression of
      hAxin strongly promoted the downregulation of wild-type beta-catenin in colon
      cancer cells, whereas mutant oncogenic beta-catenin was unaffected. The
      downregulation was increased by deletion of the APC-binding domain from Axin,
      suggesting that APC may function to derepress Axin activity. In addition, hAxin
      dramatically facilitated the phosphorylation of APC and beta-catenin by GSK3 beta
      in vitro. CONCLUSIONS: Axin acts as a scaffold upon which APC, beta-catenin and
      GSK3 beta assemble to coordinate the regulation of beta-catenin signaling.

PMID- 9601642
TI  - Suppressor of fused links fused and Cubitus interruptus on the hedgehog
      signalling pathway.
AB  - The Hedgehog (Hh) family of signalling proteins [1] mediate inductive
      interactions either directly or by controlling the transcription of other
      secreted proteins through the action of Gli transcription factors, such as
      Cubitus interruptus (Ci) [2]. In Drosophila, the transcription of Hh targets
      requires the activation of the protein kinase Fused (Fu) and the inactivation of
      both Suppressor of fused (Su(fu)) and Costal-2 (Cos-2) [3]. Fu is required for Hh
      signalling in the embryo and in the wing imaginal disc and acts also as an
      antitumorigen in ovaries [4]. All fu- phenotypes are suppressed by the loss of
      function of Su(fu) [5]. Fu, Cos-2 and Ci are co-associated in vivo in large
      complexes that are bound to microtubules in a Hh-dependent manner [6,7]. Here we
      investigate the role of Su(fu) in the intracellular part of the Hh signalling
      pathway. Using the yeast two-hybrid method and an in vitro binding assay, we show
      that Su(fu), Ci and Fu can interact directly to form a trimolecular complex, with
      Su(fu) binding to both its partners simultaneously. Su(fu) and Ci also co
      immunoprecipitate from embryo extracts. We propose that, in the absence of Hh
      signalling, Su(fu) inhibits Ci by binding to it and that, upon reception of the
      Hh signal, Fu is activated and counteracts Su(fu), leading to the activation of
      Ci.

PMID- 9601643
TI  - Evolution of the interaction between Hox genes and a downstream target.
AB  - Segmental identities along the insect body depend on the activities of Hox genes
      [1,2]. In Drosophila melanogaster, one well-studied Hox regulatory target is
      Distal-less (Dll), which is required for the development of distal limb
      structures [3]. In abdominal segments, Dll transcription is prevented when Hox
      proteins of the Bithorax Complex (BX-C) bind to cis-regulatory elements upstream
      of the Dll transcription start site [4,5]. Previous evolutionary comparisons of
      gene expression patterns suggest that this direct repression is conserved between
      Diptera and Lepidoptera, but is absent in the Crustacea [6,7]. We examined gene
      expression patterns in three orders of hexapods, all of which develop abdominal
      appendages, in order to determine when the strong repressive interaction between
      BX-C proteins and Dll appeared during evolution. In each of the species examined,
      Dll expression was initiated in abdominal cells despite the presence of high
      levels of BX-C proteins. It appears that the strong repressive effects of BX-C
      proteins on Dll expression arose relatively late in insect evolution. We suggest
      that the regulatory interaction between the BX-C genes and Dll has evolved within
      the hexapods in a complex, segment-specific manner.

PMID- 9601644
TI  - Axis determination in Xenopus involves biochemical interactions of axin, glycogen
      synthase kinase 3 and beta-catenin.
AB  - Signaling by the Wnt family of extracellular proteins is critical in a variety of
      developmental processes in which cell and tissue polarity are established [1-5].
      Wnt signal transduction has been studied mostly by the genetic approach in
      Drosophila and Caenorhabditis elegans [1,2,5], but the biochemical mechanisms
      involved remain to be elucidated. The Wnt pathway also operates during axis
      determination in vertebrates [3,5]. Frizzled receptors transduce a signal to
      Dishevelled, leading to inactivation of glycogen synthase kinase 3 (GSK3) and
      regulation of gene expression by the complex of beta-catenin with LEF/TCF
      (lymphocyte enhancer factor/T-cell factor) transcription factors [3,5]. Axin is a
      negative regulator of Wnt signaling and dorsal axial development in vertebrates
      [6]. Here, we demonstrate that axin is associated with GSK3 in the Xenopus embryo
      and we localize the GSK3-binding domain to a short region of axin. Binding of
      GSK3 correlates with the ability of axin to inhibit axial development and with
      the axis-inducing activity of its dominant-negative form (delta RGS). We also
      find that wild-type axin, but not delta RGS, forms a complex with beta-catenin.
      Thus, axin may act as a docking station mediating negative regulation of beta
      catenin by GSK3 during dorsoventral axis determination in vertebrate embryos.

PMID- 9601645
TI  - Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is
      mediated by the chemokine receptor CXCR4.
AB  - CXCR4, a seven transmembrane domain G-protein-coupled receptor for the Cys-X-Cys
      class of chemokines, is one of several chemokine receptors that can act as a co
      receptor with CD4 for the human immunodeficiency virus (HIV-1) glycoprotein gp120
      [1-3]. CXCR4 can mediate the entry of HIV-1 strains that specifically infect T
      cells, such as the IIB strain (see [4] for review). Recent reports indicate that
      gp120 can signal through CXCR4 [5] and it has been suggested that signal
      transduction, mediated by the viral envelope, might influence viral-associated
      cytopathicity or apoptosis [6]. Neuronal apoptosis is a feature of HIV-1
      infection in the brain [7,8], although the exact mechanism is unknown. Here, we
      address the possible role of CXCR4 in inducing apoptosis using cells of the hNT
      human neuronal cell line; these cells resemble immature post-mitotic cholinergic
      neurons and have a number of neuronal characteristics [9-15]. We have previously
      shown that gp120 from the HIV-1 IIIB strain binds with high affinity to CXCR4
      expressed on hNT neurons [15]. We now find that both IIIB gp120 and the Cys-X-Cys
      chemokine SDF-1 alpha can directly induce apoptosis in hNT neurons in the absence
      of CD4 and in a dose-dependent manner. To our knowledge, this is the first report
      of a chemokine and an HIV-1 envelope glycoprotein eliciting apoptotic responses
      through a chemokine receptor.

PMID- 9601646
TI  - Genetic analysis of protein kinase B (AKT) in Drosophila.
AB  - The decision between survival and death is an important aspect of cellular
      regulation during development and malignancy. Central to this regulation is the
      process of apoptosis, which is conserved in multicellular organisms [1]. A
      variety of signalling cascades have been implicated in modulation of apoptosis,
      including the phosphatidylinositol (Pl) 3-kinase pathway. Activation of Pl 3
      kinase is protective, and inhibition of this lipid kinase enhances cell death
      under several conditions including deregulated expression of c-Myc, neurotrophin
      withdrawal and anoikis [2-7]. Recently, the protective effects of Pl 3-kinase
      have been linked to its activation of the pleckstrin homology (PH)-domain
      containing protein kinase B (PKB or AKT) [8]. PKB/AKT was identified from an
      oncogene, v-akt, found in a rodent T-cell lymphoma [9]. To initiate a genetic
      analysis of PKB, we have isolated and characterized a Drosophila PKB/AKT mutant
      (termed Dakt1) that exhibits ectopic apoptosis during embryogenesis as judged by
      induction of membrane blebbing, DNA fragmentation and macrophage infiltration.
      Apoptosis caused by loss of Dakt function is rescued by caspase suppression but
      is distinct from the previously described reaper/grim/hid functions. These data
      implicate Dakt1 as a cell survival gene in Drosophila, consistent with cell
      protection studies in mammals.

PMID- 9601647
TI  - The lissencephaly gene product Lis1, a protein involved in neuronal migration,
      interacts with a nuclear movement protein, NudC.
AB  - Important clues to how the mammalian cerebral cortex develops are provided by the
      analysis of genetic diseases that cause cortical malformations [1-5]. People with
      Miller-Dieker syndrome (MDS) or isolated lissencephaly sequence (ILS) have a
      hemizygous deletion or mutation in the LIS1 gene [3,6]; both conditions are
      characterized by a smooth cerebral surface, a thickened cortex with four abnormal
      layers, and misplaced neurons [7,8]. LIS1 is highly expressed in the ventricular
      zone and the cortical plate [9,10], and its product, Lis1, has seven WD repeats
      [3]; several proteins with such repeats have been shown to interact with other
      polypeptides, giving rise to multiprotein complexes [11]. Lis1 copurifies with
      platelet-activating factor acetylhydrolase subunits alpha 1 and alpha 2 [12], and
      with tubulin; it also reduces microtubule catastrophe events in vitro [13]. We
      used a yeast two-hybrid screen to isolate new Lis1-interacting proteins and found
      a mammalian ortholog of NudC, a protein required for nuclear movement in
      Aspergillus nidulans [14]. The specificity of the mammalian NudC-Lis1 interaction
      was demonstrated by protein-protein interaction assays in vitro and by co
      immunoprecipitation from mouse brain extracts. In addition, the murine mNudC and
      mLis1 genes are coexpressed in the ventricular zone of the forebrain and in the
      cortical plate. The interaction of Lis1 with NudC, in conjunction with the MDS
      and ILS phenotypes, raises the possibility that nuclear movement in the
      ventricular zone is tied to the specification of neuronal fates and thus to
      cortical architecture.

PMID- 9601648
TI  - The helC gene encodes a putative DEAD-box RNA helicase required for development
      in Dictyostelium discoideum.
AB  - DEAD-box RNA helicases, defined by the sequence Asp-Glu-Ala-Asp (DEAD, in single
      letter amino-acid code), regulate RNA unwinding and secondary structure in an ATP
      dependent manner in vitro [1] and control mRNA stability and protein translation.
      Both yeast and mammals have large families of DEAD-box proteins, many of unknown
      function. We have disrupted a Dictyostelium discoideum gene, helC, which encodes
      helicase C, a member of the DEAD-box family of RNA helicases that shows strong
      homology to the product of the essential Saccharomyces cerevisiae gene dbp5 [2]
      and to related helicases in mouse and Schizosaccharomyces pombe. The HelC protein
      also shows weaker homology to the translation initiation factor elF-4a. Other
      DEAD-box-containing proteins, which are less closely related to HelC, have been
      implicated in developmental roles in Drosophila [3] and Xenopus laevis; one
      example is the Xenopus Vasa-like protein (XVLP) [4-6]. In Drosophila and Xenopus,
      Vasa and XVLP, respectively, are required for the establishment of tissue
      polarity during development. In yeast, DEAD-box helicases such as Prp8 [7] are
      components of the spliceosome and connect pre-mRNA splicing with the cell cycle.
      Disruption of the helC gene in D. discoideum led to developmental asynchrony,
      failure to differentiate and aberrant morphogenesis. We postulate that one reason
      for the existence of large families of homologous DEAD-box proteins in yeast,
      mammals and Dictyostelium could be that some DEAD-box proteins have
      developmentally specific roles regulating protein translation or mRNA stability.

PMID- 9601649
TI  - Apoptosis and expression of DNA repair proteins in ischaemic brain injury in man.
AB  - We examined the timing of apoptosis and the expression of the DNA repair proteins
      poly(ADP-ribose) polymerase (PARP) and Ku80 in sections of frontal and temporal
      lobes from patients who had suffered severe brain ischaemia due to a cardiac
      arrent. In situ end-labelling (ISEL) was used to detect apoptotic cells, and
      immunohistochemistry to assess PARP and Ku80. ISEL of scattered neurons and glia
      was demonstrable predominantly during the first 24 h after ischaemia. PARP and
      Ku80 immunoreactivity increased markedly after cerebral ischaemia, PARP
      particularly in the regions of greatest susceptibility to hypoxic injury: the CA1
      field of the hippocampus and the depths of neocortical sulci. The up-regulation
      of PARP is in keeping with experimental observations concerning the key role of
      this enzyme in mediating ischaemic cell death.

PMID- 9601650
TI  - Genetic mapping and haplotype analysis of oculopharyngeal muscular dystrophy.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant muscular
      dystrophy characterized by late onset ptosis, proximal muscle weakness and
      swallowing difficulties. This disease has been recently linked to chromosome
      14q11.2-q13 in French-Canadian pedigrees. We studied three unrelated American
      families with OPMD of Hispanic descent and our results indicate that in this
      ethnic group, this disease also maps to chromosome 14q11.2-q13 (marker MYH7.24;
      Zmax = 3.98; theta max = 0). These results represent an independent demonstration
      of disease linkage in a second distinct ethnic group. Furthermore, our analysis
      demonstrates a unique haplotype that is shared by affected individuals from all
      three families suggesting a founder effect for OPMD in this population. Meiotic
      recombinants and radiation hybrid mapping permit the narrowing of the critical
      region to 1 Mb which will facilitate positional cloning of the OPMD disease gene.

PMID- 9601651
TI  - SNS Na+ channel expression increases in dorsal root ganglion neurons in the
      carrageenan inflammatory pain model.
AB  - It has been suggested that hyperexcitability in dorsal root ganglion (DRG)
      neurons due to altered sodium channel expression contributes to some chronic pain
      syndromes. To understand the role of the voltage-gated sodium channel alpha-SNS
      in inflammatory pain, we investigated the expression of alpha-SNS mRNA and
      tetrodotoxin-resistant (TTX-R) sodium current in small DRG neurons, which include
      nociceptive cells, following injection of carrageenan into the hind paw of the
      rat using in situ hybridization and patch-clamp recording. alpha-SNS mRNA
      expression in DRG neurons projecting to the inflamed limb was significantly
      increased 4 days following carrageenan injection, compared with DRG neurons from
      the contralateral side or naive (uninjected) rats (mean +/- s.d. optical density
      ratio: ipsilateral/contralateral, 1.77 +/- 0.17; ipsilateral/naive, 1.88 +/-
      0.36). The amplitude of the TTX-R sodium current in small DRG neurons projecting
      to the inflamed limb was significantly larger than on the contralateral side 4
      days post-injection (31.7 +/- 3.3 vs 20.0 +/- 2.1 nA). The TTX-R current density
      was also significantly increased. These results demonstrate the increased
      expression of alpha-SNS sodium channels in small DRG neurons following injection
      of carrageenan into their projection field, and suggest that alpha-SNS is
      involved in the development of hyperexcitability associated with inflammation.

PMID- 9601652
TI  - Developmental regulation of neuroligand-induced responses in cultured
      oligodendroglia.
AB  - Using whole-cell patch-clamp techniques, we show that oligosphere-derived
      oligodendrocyte progenitor cells (OP) display GABA-, glutamate-, 5-HT-, glycine-
      and acetylcholine-gated inward currents. When OP differentiate into
      oligodendrocytes (ODC), the amplitude of peak currents elicited by saturating
      concentrations of these transmitters decreases except for 5-HT. Intracellular
      Ca2+ concentration changes induced by microperfusion of glutamate, 5-HT, TRH, met
      enkephalin and substance P were monitored using a fluo-3-based calcium imaging
      system. When OP cells differentiate into ODC, a global decrease of the proportion
      of responding cells is observed. During type-2 astrocytes commitment, this
      proportion decreases for 5-HT, TRH- and metenkephalin stimulations whereas it
      remains constant for substance P and glutamate. These data demonstrate a
      development regulation of neurotransmitter- and neuropeptide-induced responses
      within the oligodendroglial lineage.

PMID- 9601654
TI  - The mGlu receptor ligand (S)-4C3HPG protects neurons after global ischaemia in
      gerbils.
AB  - (S)-4-Carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG] is a potent competitive
      antagonist at the metabotropic glutamate receptor 1 subtype (mGlu1 receptor) and
      an agonist at mGlu2/3 receptor. We evaluated histologically the effect of this
      compound on transient global ischaemia in gerbils and observed pronounced
      neuroprotection in the CA1 layer of the hippocampus. When (S)-4C3HPG (1 microM)
      was administered intra-cerebroventricularly (i.c.v.) 20 min before clamping both
      common carotid arteries neuronal density was comparable with that in sham
      operated animals. A single injection (1 microM) 65 min after ischaemia also
      significantly reduced neuronal damage. The results suggest that metabotropic
      glutamate receptors play a role in the deleterious cascade which leads to
      neuronal damage of pyramidal cells in the CA1 layer of the hippocampus after
      transient global ischaemia.

PMID- 9601653
TI  - Schizophrenic psychoses and the CNTF null mutation.
AB  - Genetic susceptibility plays an important role in the development of
      schizophrenic psychoses, and the neural maldevelopment hypothesis is suggested by
      neuropathological and neuroimaging findings. We investigated the association
      between a null mutation in the ciliary neurotrophic factor (CNTF) gene and
      functional psychoses including schizophrenia and schizoaffective disorder. The
      frequency of mutant allele was significantly increased in patients with
      schizoaffective disorder, but not in those with schizophrenia in comparison with
      controls. The CNTF null mutation resulting in CNTF deficiency may confer
      potential susceptibility to schizoaffective disorder.

PMID- 9601655
TI  - Temporal profile of the directional tuning of the discharge of dorsal premotor
      cortical cells.
AB  - This study examined the directional modulation of dorsal premotor (PMd) cells as
      a function of time in an instructed delay, reaching task that systematically
      varied direction and accuracy constraints. In two monkeys, the activity of 150
      PMd cells was recorded and the preferred direction (PD) of the firing as a
      function of time, the PD trajectory, was calculated. Forty-one cells had nearly
      continuous significant directional tuning of at least 1 s duration (mean duration
      1694 +/- 754 ms) that began in the instructed delay period and continued into the
      movement period. The PD gradually changed in time (mean change of 47.7 +/- 40.8
      degrees), a change best described as a rotation. The change in the directional
      tuning as a function of time is consistent with the hypothesis that the PMd plays
      a role in the non-standard mapping of sensory stimuli into motor commands.

PMID- 9601656
TI  - Effects of suramin on neuroendocrine and behavioural responses to conditioned
      fear stimuli.
AB  - Conditioned fear stimuli suppress motor activity. The fear stimuli suppress
      vasopressin and facilitate oxytocin and prolactin release. These fear responses
      are impaired by selective destruction of noradrenergic neurones. Adenosine 5'
      triphosphate is co-released from noradrenergic nerve terminals with
      noradrenaline. Thus the possibility arises that the behavioural and
      neuroendocrine responses may be mediated by purinergic rather than noradrenergic
      synapses. We examined whether suramin, an inhibitor of P2 and NMDA receptors,
      blocks conditioned fear responses. Suramin injected i.c.v. 30 min before testing
      stimuli impaired conditioned fear responses. The role of purinergic P2 receptors
      in expression of the behavioural and neuroendocrine responses to conditioned fear
      stimuli is discussed.

PMID- 9601657
TI  - The tau mutation affects temperature compensation of hamster retinal circadian
      oscillators.
AB  - Neural retinas of the golden hamster (Mesocricetus auratus) express circadian
      rhythms of melatonin synthesis when cultured in constant darkness. Retinas from
      wild-type hamsters synthesize melatonin with a period close to 24 h, while
      retinas obtained from hamsters homozygous for the circadian mutation tau, which
      shortens the free-running period of the circadian activity rhythm by 4 h,
      synthesize melatonin with a period close to 20 h. The retinal circadian
      oscillators of both wild-type and tau mutant hamsters are temperature
      compensated; however, temperature compensation is adversely affected by the
      mutation.

PMID- 9601658
TI  - Auditory attention in the congenitally blind: where, when and what gets
      reorganized?
AB  - Functional reorganization of auditory attention was studied in 12 congenitally
      blind subjects and 12 controls using high-density event-related potentials during
      a highly focused dichotic listening task. Reaction times for the attend-ear
      intensity-deviant targets were markedly faster for the blind. Brain activity
      associated with sustained attention (N1 effect, Nd), and with the automatic
      detection of deviants in an unattended channel (MMN), did not exhibit
      reorganization. In contrast, marked plasticity changes were reflected in late
      auditory attentional processing (attend-ear targets), in the form of a prolonged
      negativity (200-450 ms post-stimulus) that was absent in the sighted subjects.
      The plasticity changes in the blind had a time course indicating progressive
      recruitment of parietal and then occipital regions, providing new evidence for
      cross-modal sensory reorganization in the blind.

PMID- 9601659
TI  - Acute plasticity in the human somatosensory cortex following amputation.
AB  - We studied a patient after amputation of an arm and found that in less than 24 h
      stimuli applied on the ipsilateral face were referred in a precise,
      topographically organized, modality-specific manner to distinct points on the
      phantom. Functional magnetic resonance imaging (fMRI) performed one month later
      showed that brush-evoked activity in the brain demonstrates objective signal
      changes which correlate with perceptual changes in the phantom hand. This finding
      in humans corresponds to the observations of immediate plasticity in cortical
      pathways described in animals, including primates. The results suggest that
      reorganization of sensory pathways occurs very soon after amputation in humans,
      potentially due to the unmasking of ordinarily silent inputs rather than
      sprouting of new axon terminals.

PMID- 9601660
TI  - The functional anatomy of imagining and perceiving colour.
AB  - We report two functional magnetic resonance imaging experiments which reveal
      similarities and differences between perceptual and imaginal networks within the
      single visual submodality of colour. The first experiment contrasted viewing of a
      coloured and grey-scale Mondrian display, while the second contrasted a relative
      colour judgement with a spatial task and required the generation of mental
      images. Our results show that colour perception activates the posterior fusiform
      gyrus bilaterally (area V4), plus right-sided anterior fusiform and lingual gyri,
      striate cortex (area V1), and the left and right insula. Colour imagery activated
      right anterior fusiform gyrus, left insula, right hippocampus and parahippocampal
      gyrus, but not V4 or V1. The findings reconcile neurological case studies
      suggesting a double dissociation between deficits in colour imagery and
      perception and point to anterior fusiform, parahippocampal gyri and hippocampus
      as the location for stored representations of coloured objects.

PMID- 9601661
TI  - Relationship between anxiety and serotonin in the ventral striatum.
AB  - Rats were tested in an elevated plus-maze on two consecutive days. Based on the
      percentage of time spent in the open arms on the 1st day, they were divided into
      two subgroups with either low or high anxiety levels. A post-mortem neurochemical
      analysis showed that animals with high anxiety had lower ventral striatal tissue
      levels of 5-HT. No such differences were found for 5-HT in other brain areas or
      in dopamine and norepinephrine levels. The ventral striatal 5-HT levels
      correlated with plus-maze behavior on the 2nd but not 1st day. These data suggest
      that individual differences in ventral striatal 5-HT interact with plus-maze
      behavior, which may help to explain why serotonergic drugs can have inconsistent
      effects in this paradigm.

PMID- 9601662
TI  - Immunofluorescent identification of endomorphin-2-containing nerve fibers and
      terminals in the rat brain and spinal cord.
AB  - Endomorphin-1 and -2 are potent and selective agonists for the mu-opioid receptor
      which have recently been isolated from bovine brain extracts. In the present
      study we used polyclonal antibodies specific for endomorphin-2 to determine its
      immunocytochemical distribution in the rat brain and spinal cord Endomorphin-2
      like immunoreactivity was confined to varicose fibers with an overall discrete
      distribution within the central nervous system. The immunostaining was completely
      abolished by preincubation of the antiserum with endomorphin-2 but not with
      endomorphin-1. Endomorphin-2-like immunoreactivity was enriched in many but not
      all brain regions known to contain dense mu-opioid receptors, including nucleus
      accumbens, septum, midline thalamic nuclei, hypothalamic and amygdala nuclei,
      locus coeruleus, periaqueductal gray and spinal cord dorsal horn. In contrast,
      endomorphin-2 was absent from the cortex, striatum, hippocampus, nucleus of the
      solitary tract and dorsal root ganglia. Dual-labeling experiments revealed that
      endomorphin-2-immunoreactive nerve fibers did not co-contain any other opioid
      peptide. Thus, the present findings strongly suggest that endomorphin-2 may be a
      natural ligand for the mu-opioid receptor likely to be involved in the modulation
      of nociceptive transmission and reward-seeking behavior.

PMID- 9601663
TI  - Differential interactions of MAP2, tau and MAP5 during axogenesis in culture.
AB  - The subcellular interactions of the neuronal microtubule-associated proteins tau,
      MAP2 and MAP5 were determined in cultured rat hippocampal neurons using
      differential detergent extraction and laser scanning microscopy. Axon development
      correlated with a transition from a MAP2-actin filament interaction to a MAP2
      microtubule association and binding of tau to the distal axon. Tau and MAP2
      binding specifically increased in the axon and the minor neurites, respectively.
      No compartment-specific association of MAP5 was observed. Tau binding preceded
      the accumulation of microtubules at the distal axon which represented a
      characteristic event during axogenesis. The data provide evidence for a role of
      MAP2 in regulating microfilament-microtubule interactions during neurite
      formation and of tau in organizing microtubules at the distal axon.

PMID- 9601664
TI  - Human hippocampal long-term sustained response during word memory processing.
AB  - Temporal behavior of activation associated with the neural substrate of human
      memory function was investigated during and after an auditorily instructed word
      memory task using multislice functional magnetic resonance imaging. The
      hippocampal formation, which is involved in human memory function, displayed a
      long-term sustained response that persisted significantly (approximately 90 s)
      beyond the duration of the memory task. This sustained period was approximately
      two-fold longer than the duration of the post-task activation observed in
      auditory areas and Broca's area, which are involved in the phonological loop of
      the verbal working memory. These observations suggest that the hippocampal memory
      processing involves sustained activation in the transitional function for the
      long-term memory over the working memory period.

PMID- 9601665
TI  - Bcl-2 and Bax protein expression in neurofibrillary tangles in progressive
      supranuclear palsy.
AB  - Double-labeling immunohistochemistry to Bcl-2 and Bax and to tau protein was
      examined in the brains of patients with progressive supranuclear palsy (PSP) to
      study the possible relationship between the expression of Bax and Bcl-2 proteins
      and neurofibrillary tangle formation. No differences between Bcl-2 and Bax
      immunoreactivity in neurons of the brain stem were observed in PSP patients and
      controls. Moreover, the intensity of Bcl-2 and Bax immunoreactivity was similar
      in tangle-bearing and non-tangle-bearing neurons in PSP patients. These results
      suggest that Bcl-2 and Bax are probably not implicated in neurofibrillary tangle
      formation in PSP.

PMID- 9601666
TI  - The medical nucleus of the solitary tract mediates the trigeminally evoked
      pressor response.
AB  - The present study examined whether the nucleus of the solitary tract (NTS) plays
      a role in mediating the trigeminally evoked pressor response which occurs after
      noxious perturbation of the nasal mucosa or electrical stimulation of the
      ethmoidal nerve (EN5). We recorded arterial blood pressure responses to EN5
      stimulations before and after injections of the calcium channel blocker CoCl2
      into the NTS. Unilateral and bilateral injections of CoCl2 into the medial NTS
      resulted in significant blockade (p < 0.05 and p < 0.01, respectively) of the EN5
      evoked pressor responses. Recovery of the pressor responses was observed 15-25
      min after the CoCl2 injections. CoCl2 injections into the caudal commissural NTS
      remained largely ineffective with respect to blocking the EN5-evoked pressor
      responses. These findings strongly suggest that the medial NTS is a crucial link
      for the trigeminally induced pressor response.

PMID- 9601667
TI  - Expression of an oscillating interferon-gamma receptor in the suprachiasmatic
      nuclei.
AB  - The suprachiasmatic nuclei serve as the dominant circadian pacemaker in the
      mammalian brain, regulating daily behavioral, physiological and hormonal rhythms.
      In the ventrolateral parts of these nuclei, the receptor for the key
      immunoregulatory molecule interferon-gamma (IFN-gamma) was detected in the rat
      brain. The cellular localization of the IFN-gamma receptor corresponded to
      neuronal elements. Expression of the receptor followed a diurnal rhythm with a
      peak at zeitgeber time 15. This peak coincided with an enhanced expression of
      janus kinase 1 and 2 as well as the signal transducer and activator of
      transcription 1, which constitute the main intracellular signaling pathway of IFN
      gamma. This is the first study to show expression of the receptor of an immune
      modulatory molecule in the pacemaker of the biological clock, which, thus, may be
      influenced by immune system signal molecules.

PMID- 9601668
TI  - GABAA receptor blockade inhibits A beta fibre evoked wind-up in the arthritic
      rat.
AB  - To clarify the mechanisms of allodynia we have examined whether 'wind-up' of
      nociceptive withdrawal reflexes (NWR), a phenomenon characteristic of nociceptive
      C fiber spinal processing, can be mimicked by stimulation of tactile A beta
      fibers in monoarthritic decerebrate spinal rats. Knee joint monoarthritis was
      induced by carrageenan/kaolin under halothane anaesthesia 5 h before recordings.
      In arthritic, but not in control rats, wind-up of NWR of the semitendinosus
      muscle could be evoked by repeated stimulation of A beta fibres. By contrast,
      peroneus longus reflexes did not exhibit marked wind-up. Bicuculline (0.03-0.3
      mg/kg, i.v.) dose-dependently inhibited this wind-up. Hence, reflex wind-up can
      be elicited by tactile A beta fibers in arthritis rats through a GABAA dependent
      mechanism.

PMID- 9601669
TI  - Dextromethorphan potentiates the effect of morphine in rats with peripheral
      neuropathy.
AB  - Neuropathic pain responds poorly to opioids. We now report that combination of
      systemic morphine (2 mg/kg) and dextromethorphan (45 mg/kg), a clinically
      available antitussive with NMDA-antagonist properties, markedly alleviated
      mechanical and cold allodynia-like behavior in a rat model of peripheral
      mononeuropathy. Neither drug produced a significant effect on its own at these
      doses. The anti-allodynic effect of morphine plus dextromethorphan was reversed
      by naloxone. The present results suggest that a combination of NMDA-antagonist
      and opiates might be effective in treating neuropathic pain. Furthermore, the
      effect of this drug combination is mainly mediated via opioid receptors.

PMID- 9601670
TI  - Intraspinal grafting of fibroblasts genetically modified by recombinant
      adenoviruses.
AB  - Intracerebral or intraspinal grafting of genetically modified primary fibroblasts
      has been shown to enhance functional recovery in several models of CNS disease,
      including spinal cord injury. Most of these studies utilized retrovirus vectors.
      In this report, we describe in vitro conditions for genetically modifying primary
      fibroblasts with recombinant adenovirus vectors carrying the lacZ or green
      fluorescent protein (GFP) genes. As intraspinal allografts in animals
      immunosuppressed by cyclosporin A, the genetically modified cells survived and
      expressed the transgenes for at least 2 months. We conclude that recombinant
      adenovirus vectors are efficient and convenient tools for ex vivo gene therapy in
      the CNS.

PMID- 9601671
TI  - Profound inhibition of cardiomotor neurons in the rat rostral ventrolateral
      medulla by nociceptin (orphanin FQ).
AB  - Nociceptin (orphanin FQ), the newly discovered endogenous ligand for the opioid
      receptor like-1 receptor, profoundly inhibited spontaneous discharges of neurons
      in the rostral ventrolateral medulla (RVLM) in rat brain slices. This inhibition
      was concentration-dependent (0.3, 1, 3 and 10 nM) and insensitive to
      pharmacological blockade of traditional opioid receptors by naloxone. Moreover,
      nociceptin injected into the RVLM (10 nM, 0.1 microliter) in anesthetized rats
      decreased arterial blood pressure and heart rate by 31% and 15%, respectively.
      The data obtained in vitro and in vivo suggest that nociceptin has powerful
      effects on the RVLM neurons involving central control of cardiovascular activity.
      The negative regulation of cardiovascular activity by nociceptin is not mediated
      through typical naloxone-sensitive opioid receptors.

PMID- 9601672
TI  - Organization of common peroneal nerve motoneurones in the rat and monkey: a
      comparative study.
AB  - The motoneurones with axons in the common peroneal nerve (CPN) of the rat and
      monkey were examined using retrograde labelling with horseradish peroxidase
      (HRP). In both species, the CPN motoneurone pool was localized in the
      dorsolateral part of the ventral horn of the spinal cord. In the rat, the
      labelled motoneurones were located between the L3 and L6 spinal segments whereas
      in the monkey, they extended from the caudal end of L4 to the L6 spinal segments.
      In both species the majority of the labelled neurones were located within the L5
      segment. The mean number of the CPN motoneurones in the rat and monkey was 458
      and 1148, respectively. A bimodal size distribution of motoneurones was found in
      both species.

PMID- 9601673
TI  - Gamma subunit dependent modulation by nitric oxide (NO) in recombinant GABAA
      receptor.
AB  - The effect of nitric oxide (NO) on GABA induced Cl- current of recombinant GABAA
      receptors was studied. Either alpha 1 beta 2 gamma 2s or alpha 1 beta 2 subunit
      mRNAs synthesized from cDNA of mouse brain were injected into Xenopus oocytes and
      functional GABAA receptors were expressed. GABA-induced Cl- current was measured
      with the two electrode voltage clamp technique. The NO donor NOC-18 reduced the
      GABA-induced Cl- current in the alpha 1 beta 2 gamma 2s subunit receptor in a
      dose-dependent manner. In alpha 1,beta 2 subunit receptor, NOC-18 had no effects
      on GABA-induced currents at low concentrations but showed potentiation at high
      concentration. These effects were antagonized by the NO extinguisher, carboxy
      PTIO. The cGMP analogue 8-Br-cGMP failed to induce NO-like effects. NO directly
      acts at the GABAA receptor and the gamma 2s subunit is involved in its action.

PMID- 9601674
TI  - Effects of combined BDNF and GDNF treatment on cultured dopaminergic midbrain
      neurons.
AB  - Neural transplantation is an experimental therapy for Parkinson's disease.
      Pretreatment of fetal donor tissue with neurotrophic factors may improve survival
      of grafted dopaminergic neurons. Free-floating roller tube cultures of fetal rat
      ventral mesencephalon were treated with brain-derived neurotrophic factor (BDNF),
      glial cell line-derived neurotrophic factor (GDNF), or a combination of both.
      Dopamine content of the culture medium, the number of tyrosine hydroxylase
      immunoreactive neurons, and culture volumes were moderately increased in the BDNF
      and GDNF-treated cultures but significantly increased by 6.8-, 3.2- and 2.4
      fold, respectively after treatment with the combination of both factors. We
      conclude that pretreatment of dopaminergic tissue in culture with a combination
      of BDNF and GDNF may be an effective means to improve the quality of tissue prior
      to grafting.

PMID- 9601675
TI  - BMPR-II expression and OP-1 effects in developing chicken retinal explants.
AB  - Low-stringency PCR was used to isolate the chicken homologue of the human bone
      morphogenetic protein receptor type II (BMPR-II). In situ hybridization localized
      mRNA expression for this serine/threonine kinase receptor. It was weakly
      expressed in the vitreal side of the neural retina at E6. In the E7 chicken,
      fairly strong labelling was found in cells of the internal part of the neural
      retina. At E9, strong labelling was found in the region of the retinal ganglion
      cells. Explants of E6 retina exposed to osteogenic protein-1 (OP-1/BMP-7),
      exhibited dense retinal fibre outgrowth. This suggests that BMPR-II may form a
      signalling receptor complex important for retinal development. OP-1 and related
      ligands may serve functions supplementary to those of neurotrophins.

PMID- 9601676
TI  - Over-expression of NGF in skin causes formation of novel sympathetic projections
      to trkA-positive sensory neurons.
AB  - Previous studies have shown that transgenic mice over-expressing NGF in the skin
      have novel sympathetic 'basket-like' projections to sensory neurons similar to
      that seen in models of chronic pain. Since only a subset of sensory neurons in
      the NGF-transgenic mice received the sympathetic projections, we hypothesized
      that sympathetic sprouting was targeted to those neurons affected by increased
      levels of NGF. To test this, double-label immunohistochemistry for the NGF
      receptor (trkA) and sympathetic baskets was performed. Thirty-nine percent of all
      neurons in transgenic trigeminal ganglia were trkA-positive. Moreover, of the
      population of sensory neurons that received sympathetic input, 84% were trkA
      positive. These results indicate that retrogradely transported NGF can induce and
      direct growth of sympathetic axons in vivo.

PMID- 9601677
TI  - An acid sensing ion channel (ASIC) localizes to small primary afferent neurons in
      rats.
AB  - The acid sensing ion channel (ASIC) identified in rat brain and spinal cord is
      potentially involved in the transmission of acid-induced nociception. We have
      developed polyclonal antisera against ASIC, and used them to screen rat brain and
      spinal cord using immunocytochemistry. ASIC-immunoreactivity (-ir) is present in
      but not limited to the superficial dorsal horn, the dorsal root ganglia (DRG) and
      the spinal trigeminal nucleus, as well as peripheral nerve fibers. These
      observations, combined with the disappearance of ASIC-ir following dorsal
      rhizotomy, suggest localization of ASIC to primary afferents. DRG ASIC-ir co
      localizes with substance P (SP) and calcitonin gene-related peptide (CGRP)-ir in
      small capsaicin-sensitive cell bodies, suggesting that ASIC is poised to play a
      role in the transduction of noxious stimuli.

PMID- 9601678
TI  - Human cortical responses evoked by dichotically presented tones of different
      frequencies.
AB  - Behavioral and patient studies have suggested that during dichotic listening the
      ipsilateral auditory pathways are strongly inhibited, so that each hemisphere is
      treats the sound coming to the contralateral ear. We analysed the auditory N100m
      neuromagnetic evoked response following passive listening of dichotic tones of
      different frequencies. We found that the N100m in each hemisphere depended on
      both ipsilateral and contralateral stimuli, revealing no strong inhibition of
      ipsilateral pathways. The N100m increased with the interaural frequency disparity
      and was reduced as both ears received identical stimuli. The results can be
      explained by the existence of a frequency-dependent excitatory/inhibitory
      organization of the auditory cortex, as has been described in the cat. We suggest
      that the N100m might also reflect automatic processes involved in multiple-stream
      perception.

PMID- 9601679
TI  - Changes in mitochondrial Ca2+ homeostasis in primary sensory neurons of diabetic
      mice.
AB  - Changes in neuronal Ca2+ homeostasis were studied on freshly isolated dorsal root
      ganglion neurons of adult control mice and mice with streptozotocin (STZ)-induced
      diabetes. The cytoplasmic free Ca2+ concentration ([Ca2+]in) was measured using
      indo-1 based microfluorimetry. The participation of mitochondria in [Ca2+]in
      homeostasis was determined by investigation of changes which occurred after
      addition of mitochondrial protonophore (CCCP) to the extracellular solution. In
      control cells 10 microM CCCP applied before membrane depolarization induced an
      increase of the amplitude of depolarization-induced [Ca2+]in transients and
      disappearance of their delayed recovery, indicating the participation of
      mitochondria in fast uptake of Ca2+ ions from the cytosol during the peak of the
      transient and subsequent slow release them back during its decay. In diabetic
      animals the increase of the peak transient amplitude under the action of CCCP
      became diminished in small (nociceptive) neurons and the delayed elevation of
      [Ca2+]in disappeared in both large and small neurons. It is concluded that in
      diabetic conditions substantial changes occur in the Ca2+ homeostatic functions
      of mitochondria, manifested by decreased Ca2+ uptake in small neurons and
      depressed Ca2+ release into the cytosol in all types of neurons.

PMID- 9601680
TI  - Temporal structure of implicit motor imagery in visual hand-shape discrimination
      as revealed by MEG.
AB  - We investigated the spatio-temporal brain activity on the time scale of several
      milliseconds related to the mental rotation task requiring judgements of hand
      orientation, using a whole-cortex MEG (magnetoencephalography) system. Neuronal
      activity in the visual cortex was observed approximately 100-200 ms from stimulus
      onset, and that in inferior parietal lobe followed (after 200 ms). Both of these
      activities showed a contralateral dominance to visual stimulus hemifield.
      Premotor activity started later than the inferior parietal lobe activity, and
      these activities partially overlapped. Activity in primary motor and/or
      motosensory areas was observed in some subjects. The whole-cortex neuromagnetic
      measurements provided the time course of activity in the human brain associated
      with the implicit motor imagery: visual cortex-->inferior parietal lobe<-
      >premotor cortex. This process is considered to be the transformation process of
      retinotopic locations into a body-centered reference frame necessary for the
      mental rotation task.

PMID- 9601681
TI  - Astrocytes protect against X-ray-induced neuronal toxicity in vitro.
AB  - The role of neuronal damage in the radiation-induced CNS injury resulting from
      brain tumor therapy remains poorly understood. To begin to define the
      radioresponse of neurons, the survival of rat cortical neuron cultures was
      investigated. Neuronal survival was reduced by approximately 40% 24-48 h after
      irradiation with 3.5 Gy. The addition of the free radical scavenger NAC after
      irradiation increased neuronal survival. Neurons were also significantly less
      sensitive to radiation in co-cultures with astrocytes or in the presence of
      astrocyte-conditioned medium. Medium conditioned on astrocytes was found to
      acquire significant free radical scavenging capability. However, this antioxidant
      property does not appear to be responsible for neuronal radioprotection. The
      ability of astrocytes to reduce radiation-induced neuronal toxicity appears to be
      mediated by a soluble protein(s) of mol. wt > 10 kDa.

PMID- 9601682
TI  - 5-HT2A receptor gene promoter polymorphism--1438G/A and mood disorders.
AB  - A 5-HT2A receptor promoter polymorphism, -1438G/A, was reported to be
      significantly increased in patients with anorexia nervosa when compared with
      controls. In practice, many patients with anorexia nervosa suffer from mood
      disorders. Furthermore, 5-HT2A receptors are thought to play a role in the
      etiologies of mood disorders. Thus, we studied the polymorphism in 95 Japanese
      patients with mood disorders and 106 healthy Japanese controls. The allele
      frequency for the -1438G/A polymorphism did not differ between the patients and
      controls. In addition, the genotype frequencies did not differ according to the
      subdiagnosis, age of onset, family history of psychiatric illness or suicide
      attempts.

PMID- 9601683
TI  - Immunomagnetic isolation of human developing motor neurons.
AB  - Human motor neuron (MN) isolation provides a critical tool to study
      neurophysiological properties and the effects of molecules of clinical relevance
      on isolated neurons. We developed an immunomagnetic separation technique based on
      specific MN antigen recognition for nerve growth factor receptor (p75-NGFR). We
      cultured an average of 250,000 cells from the anterior horns of a single cord
      (four specimens at postconception Weeks 6.0, 7.2, 8.0, and 8.3). At day 7 in
      vitro (DIV), choline acetyltransferase (ChAT) and/or p75-NGFR-expressing cells
      (MNs) represented 72 +/- 2% of the total growing cells. MNs survived for at least
      4 weeks in biochemically defined medium. The immunomagnetic separation method has
      been demonstrated to be effective, reproducible, and quantitative for separation
      of MNs.

PMID- 9601684
TI  - Specific binding of L-triiodothyronine modulates Na(+)-K(+)-ATPase activity in
      adult rat cerebrocortical synaptosomes.
AB  - Interactions of L-triiodothyronine (T3) in adult rat cerebrocortical synaptosomes
      were studied in vitro. Scatchard plot analysis revealed two sets of T3 binding
      sites. The degree of saturation of T3 binding sites (putative receptor)
      correlated well with the dose-dependent inhibition of Na(+)-K(+)-ATPase activity
      in synaptosomes. The relative binding affinities and relative inhibition of
      enzyme activities for different TH analogues were L-T3 > T3-amine > TRIAC = L-T4
      > r-T3 > T2 and L-T3 > T3-amine > TRIAC > L-T4 > r-T3 > T2, respectively. The
      present study demonstrates the nature of inhibition of synaptosomal Na(+)-K(+)
      ATPase activity may be as a function of T3 occupancy of synaptosomal receptor
      sites in adult mammalian brain.

PMID- 9601685
TI  - Impaired associative learning in chronic fatigue syndrome.
AB  - Patients with chronic fatigue syndrome (CFS) report cognitive difficulties
      (impaired attention, memory and reasoning). Neuropsychological tests have failed
      to consistently find cognitive impairments to the degree reported by CFS
      patients. We tested patients with CFS and sedentary controls in protocols
      designed to measure sensory reactivity and acquisition of the classically
      conditioned eyeblink response. Patients with CFS exhibited normal sensitivity and
      responsivity to acoustic stimuli. However, CFS patients displayed impaired
      acquisition of the eyeblink response using a delayed-type conditioning paradigm.
      Sensitivity and responsivity to the airpuff stimulus were normal. In the absence
      of sensory/motor abnormalities, impaired acquisition of the classically
      conditioned eyeblink response indicates an associative deficit. These data
      suggest organic brain dysfunction within a defined neural substrate in CFS
      patients.

PMID- 9601686
TI  - Expression of mRNAs encoding BDNF and its receptor in adult rat hypothalamus.
AB  - We used a digoxigenin-UTP-labeled cRNA probe with in situ hybridization and
      Northern blot analysis to investigate the localization of brain derived
      neurotrophic factor (BDNF) mRNA and expression of its different transcripts in
      adult rat hypothalamus. As the BDNF gene is under the control of alternative
      multiple promoters, which provide tissue-specific gene expression, we studied
      whether these transcripts were expressed in adult hypothalamus. Our data revealed
      two novel sources of hypothalamic BDNF mRNA: the supraoptic and periventricular
      nuclei. In addition, we observed the expression of transcripts from exons, I, II
      and III as well as the presence of 1.6 and 4.2 kb BDNF mRNAs. Finally, our
      findings confirmed expression of mRNA encoding neurotrophins receptors in the
      hypothalamus.

PMID- 9601687
TI  - Analgesic activity of orphanin FQ2, murine prepro-orphanin FQ141-157 in mice.
AB  - Orphanin FQ/nociceptin (OFQ/N) is generated from a larger precursor peptide,
      prepro-orphanin FQ (ppOFQ). Within the sequence of murine ppOFQ is another
      putative heptadecapeptide, orphanin FQ2 (OFQ2), corresponding to murine ppOFQ141
      157. OFQ2 was a potent analgesic given either supraspinally (ED50 0.5 microgram,
      i.c.v.) or spinally (ED50 0.7 microgram, i.t.). As with opioids and OFQ/N, OFQ2
      analgesia was enhanced by blockade of sigma receptors with haloperidol, which
      increased the potency of the peptide over 10-fold. Supraspinal OFQ2 analgesia was
      readily reversed by naloxone, implying that it activated opioid systems. Spinal
      OFQ2 analgesia was insensitive to naloxone. OFQ2 also inhibited gastrointestinal
      transit. Together, these studies suggest that OFQ2 may be a relevant neuropeptide
      with important physiological actions.

PMID- 9601688
TI  - Hyperalgesia and allodynia induced by intrathecal (RS)-dihydroxyphenylglycine in
      rats.
AB  - To investigate the role of Group I mGluRs in allodynia and hyperalgesia, we
      examined the behavioural responses of rats to noxious and non-noxious mechanical
      and thermal stimuli following intrathecal (i.t.) treatment (25 nmol) with the
      selective mGluR1/5 agonist, (RS)-dihydroxyphenylglycine ((RS)-DHPG). (RS)-DHPG
      administration produced a persistent decrease in response latency on a 48 degrees
      C hotplate, a reduction in the 50% response threshold to von Frey hairs, and an
      increase in responses to a tail pinch. These data suggest that activation of
      spinal mGluR1/5 receptors plays a role in the development of persistent allodynia
      and hyperalgesia associated with tissue or nerve injury.

PMID- 9601689
TI  - Neuronal apoptosis is associated with a decrease in tau mRNA expression.
AB  - Apoptosis is a programmed cell death that occurs during the development of the
      nervous system and in neurodegenerative disorders. Tau protein is a microtubule
      associated protein which promotes microtubule polymerization and stabilization.
      Apoptosis was induced in primary neuronal cultures by glutamate exposure (200
      microM, 15 min) or by serum deprivation, and tau mRNA levels were studied by
      quantitative in situ hybridization in apoptotic and non apoptotic neurons.
      Compared to controls, tau mRNA expression was decreased in apoptotic neurons
      produced by excitotoxicity or trophic support withdrawal. Under these conditions,
      resistant neurons to apoptosis display either increased tau mRNA levels after
      glutamate exposure or a stable tau mRNA expression after serum deprivation. In
      conclusion, in this in vitro model, neurons which are resistant and sensitive to
      apoptosis can be differentiated according to tau mRNA expression.

PMID- 9601690
TI  - Adrenalectomy-induced apoptosis and glial responsiveness during ageing.
AB  - Cell death by apoptosis occurs in mature neurones of adult rat dentate gyrus
      following adrenalectomy. In these studies, apoptosis in the dentate gyrus was
      induced 3 days after adrenalectomy in male Fischer 344 rats ranging in age from 2
      3 to 24-26 months. Glial fibrillary acidic protein and transforming growth factor
      beta 1 mRNAs were increased in dentate gyrus of all age groups after
      adrenalectomy, but there was no effect of age on these responses. Furthermore,
      corticosterone treatment in the drinking water of adrenalectomized rats prevented
      both cell death and increases in glial mRNAs in all age groups that were tested
      (up to 16-18 months). Therefore, adrenalectomy-induced apoptosis can be used to
      study mechanisms of cell death and survival in aged brain.

PMID- 9601691
TI  - AMPA and NMDA receptor-dependent spinal LTP after nociceptive tetanic
      stimulation.
AB  - LTP is often studied as a model of synaptic plasticity. Plasticity in pain
      control systems may involve mechanisms similar to those involved in learning. We
      recently reported LTP of both the A beta and C-fibre evoked responses of single
      dorsal horn neurons after a tetanic stimulation of the sciatic nerve, lasting for
      at least 6 h. In the present paper we show that identical stimulation induced LTP
      only of the C-fibre evoked response after blockade of muscular contractions
      during the tetanus. The C-fibre evoked response increased significantly less
      after pretreatment with either the AMPA antagonist NBQX or the NMDA antagonist D
      AP5 (mean increase 33%) than in untreated animals (105%, p < 0.001), indicating
      that both AMPA and NMDA receptor stimulation are involved in the induction of
      LTP.

PMID- 9601692
TI  - Neuroprotective effects of a systemically active group II metabotropic glutamate
      receptor agonist LY354740 in a gerbil model of global ischaemia.
AB  - The neuroprotective effects of a novel Group II metabotropic glutamate receptor
      (mGluR) agonist, LY354740, have been evaluated in a gerbil model of global
      ischaemia. When administered at 50 mg/kg, i.p., 30 min and 6 h after a 3 min
      period of bilateral carotid artery occlusion (BCAO), the compound reduced the
      damage to CA1 hippocampal neurones to a significant level. However, when the
      ischaemic insult was made more severe, by increasing the period of occlusion to 4
      and 5 min, the neuroprotective effects of LY354740 were reduced. From these
      findings, it would appear that Group II mGluRs may play a role in ischaemic
      damage in the gerbil hippocampus and that agonists at these receptors are
      potential neuroprotective agents.

PMID- 9601693
TI  - Neuropsychological evidence of the functional integration of visual, auditory and
      proprioceptive spatial maps.
AB  - We infer the functional integration of the visual, auditory and proprioceptive
      spatial maps from the behaviour of a patient (G.A.) with left visual neglect,
      i.e. a derangement of visual space representation. G.A. was required to point
      manually to left, centre or right acoustic stimuli, under visual control or
      blindfolded, with the responding hand (left or right) located either on the left,
      centre or right space. G.A.'s manual pointing responses to left auditory stimuli
      were strongly influenced by the visual spatial information and by the
      proprioceptive spatial information related to the position of the responding
      effector. In the visual control condition, when the patient performed the task
      with the left effector located on the left, pointing responses to left auditory
      stimuli were shifted towards the right intact visual space. In contrast, when the
      visual spatial information was rendered less salient, i.e. in the blindfolded
      condition, and the effector was again located on the left, manual pointing
      responses were confined to the previously ignored left space. These findings are
      consistent with the view that the acoustic representation is modulated by the
      impaired visual representation and by the proprioceptive spatial map related to
      the position of the responding effector.

PMID- 9601694
TI  - mGluR activation reveals a tonic NMDA component in inflammatory hyperalgesia.
AB  - Metabotropic glutamate receptors (mGluRs) have been shown to contribute to
      nociceptive processing in the spinal cord. We have investigated the pharmacology
      of the mGluR agonist (1S,3R)-ACPD during inflammatory hyperalgesia in an in vitro
      preparation of the juvenile rat hemisected spinal cord. Superfusion of (1S,3R)
      ACPD produced a concentration-dependent ventral root depolarization in naive and
      hyperalgesic animals with no significant difference in EC50 values (55.5 +/- 6.36
      microM and 51.0 +/- 5.76 microM, respectively, n = 4). However, the amplitude of
      the maximum response was significantly enhanced by 23% in hyperalgesic compared
      with naive animals. The NMDA receptor antagonist D-AP5 reversed this effect,
      leaving the (1S,3R)-ACPD dose-response curve unchanged in naive animals. These
      results suggest a tonic NMDA component in the spinal cord during inflammatory
      hyperalgesia.

PMID- 9601695
TI  - Evidence for an endogenous clock in the retina of rainbow trout: I. Retinomotor
      movements, dopamine and melatonin.
AB  - The purpose of the present study was to investigate patterns of circadian
      rhythmicity in the retina of a salmonid fish, the rainbow trout (Oncorhynchus
      mykiss). In a first attempt to show both morphological and neurochemical
      variations during light/dark conditions (LD) and during continuous darkness (DD),
      we investigated retinomotor movements and the associated regulatory transmitters,
      dopamine and melatonin. All parameters studied showed patterns of rhythmicity in
      LD and DD, clearly indicating the presence of an endogenous clock in the rainbow
      trout eye. The most salient variations of all parameters studied were found at
      the transitions from light to dark and vice versa in LD and from subjective day
      to subjective night and vice versa in DD. The amplitudes of rhythms compared
      between LD and DD were similar in pigment index, whereas a clear reduction was
      found for cone index, dopamine and melatonin.

PMID- 9601696
TI  - Membrane properties of giant neurons in the caudal pontine reticular formation in
      vitro.
AB  - The intrinsic membrane properties of giant neurons of the caudal pontine
      reticular nucleus (PnC) were evaluated in a rat brain slice preparation. These
      neurons show low RP levels, long membrane time constants, low membrane
      resistance, tonic AP firing, and a lack of rectification behavior. The results
      are compared to those measured in adjacent areas of the reticular formation and
      discussed for their impact on triggering and modulating the acoustic startle
      response.

PMID- 9601697
TI  - Serotonin-1B agonists induce compartmentally organized striatal Fos expression in
      rats.
AB  - The 5HT1B agonist RU24969 (2.5-5.0 mg/kg) and anpirtoline (2.0 mg/kg) induced a
      striking increase in striatal Fos-like immunoreactivity in rats. In the rostral
      and dorsal regions of the striatum staining was dense and relatively homogeneous.
      In the ventral region of the striatum at more caudal levels, however, both drugs
      induced staining in patches which were in register with the opiate receptor rich
      striosomes. The effects of RU24969 could not be antagonized by the selective
      5HT1A antagonist p-MPPI and little or no striatal Fos expression could be
      observed after injections of the selective 5HT1A agonist 8-OHDPAT or the
      selective 5HT3 antagonist MDL-72222.

PMID- 9601698
TI  - fMRI reveals amygdala activation to human faces in social phobics.
AB  - Functional magnetic resonance imaging was used to determine the activation of the
      amygdala while seven social phobics and five healthy controls were exposed to
      slides of neutral faces as well as aversive odor stimuli. The amygdala was
      selectively activated in the social phobics during presentation of the face
      stimuli. The data show for the first time that the amygdala is active in human
      phobics when they are exposed to potentially fear-relevant stimuli. Further
      research is needed to determine the extent to which overactivation of the
      amygdala precedes or is a consequence of phobia.

PMID- 9601699
TI  - Intraneuronal Ca2+ stores act mainly as a 'Ca2+ sink' in cerebellar granule
      neurones.
AB  - The role of intracellular Ca2+ stores during depolarization-evoked Ca2+ signals
      in cultured cerebellar granule neurones was assessed by depletion of the stores
      with a specific inhibitor of the endoplasmic reticulum Ca2+ pump: thapsigargin
      (TG, 0.7 microM). The maximal rate of [Ca2+]i increase, measured as the first
      order differential of the [Ca2+]i trace, increased directly in proportion to the
      increasing KCl concentration (in the range 20-90 mM) or, for a given KCl
      concentration (50 mM), to the levels of pre-stimulation [Ca2+i (range 25-100 nM
      Ca2+). Both these relationships were unaffected by TG. In contrast, the amplitude
      of the KCl-evoked response for KCl concentrations > 30 mM (inducing an increase
      in [Ca2+]i > 400 nM) was increased in the presence of TG.

PMID- 9601700
TI  - Stereoscopic depth perception in the owl.
AB  - It is unclear whether the neural algorithm that underlies stereoscopic vision in
      birds incorporates both low level (camouflage breaking) and high level (depth
      ordering) comparisons of information available to each of the eyes. Both visual
      functions were successfully tested by examining transitive inference performance
      in two barn owls trained to discriminate static Julesz random dot stereograms,
      thus demonstrating a capacity to detect relative depth using fine retinal
      disparity as the sole cue for discrimination. Our behavioral tests provide strong
      evidence that the barn owl possesses global stereopsis comparable to that found
      in the macaque monkey--the owl's best stereoacuity was 2 min of arc.

PMID- 9601701
TI  - The cDNA cloning and ontogeny of mouse alpha-synuclein.
AB  - Alpha-synuclein has been implicated in the pathogenesis of Parkinson's disease.
      To investigate the role of alpha-synuclein in the brain, the cDNA clone encoding
      the mouse cognate of the human alpha-synuclein was isolated from a mouse brain
      cDNA library. The open reading frame coded for 140 amino acids that share 95%
      identity with human alpha-synuclein. Northern blot analysis showed that alpha
      synuclein mRNA was primarily expressed in brain and spleen of adult mouse. In
      situ hybridization histochemistry revealed the highest expression of alpha
      synuclein mRNA in the hippocampal formation and neocortex of the adult mouse.
      alpha-Synuclein mRNA expression in the brain was first observed in the
      hippocampus and neocortex on postnatal day 1. Levels of alpha-synuclein mRNA in
      these forebrain areas were nearly maximal at postnatal day 7 and remained
      relatively high until the adult stage. alpha-Synuclein mRNA was expressed in the
      liver transiently during embryogenesis.

PMID- 9601702
TI  - Beta-amyloid induced reduction in synaptic transmission is reversed by inhibitors
      of nitric oxide synthase.
AB  - beta-Amyloid has been shown to be neurotoxic in vivo and in vitro. Free radical
      production and subsequent lipid oxidation after beta-amyloid application have
      been observed in vitro and are considered to be factors that contribute to the
      neurotoxicity. Field recordings in the area CA1 for 3 weeks showed a dose
      dependent effect on amplitude after intracerebroventricular (i.c.v.) injections
      of 1, 5 or 10 nmol beta-amyloid (25-35). The nitric oxide synthase inhibitors 7
      nitro indazole (30 mg/kg, i.p.) and 1-(2-trifluoromethylphenyl)imidazole (150
      nmol, i.c.v.) which preferentially inhibit the neuronal isoform prevented this
      beta-amyloid-induced decay of synaptic transmission. The protective effect of
      these inhibitors was reversed by L-arginine (200 mg/kg, i.p.). The results
      support the theory that nitric oxide production contributes to beta-amyloid
      induced neuronal degeneration or reduction of neurotransmission.

PMID- 9601703
TI  - Effects of a traumatic neocortical lesion on cerebral metabolism and gene
      expression of rats.
AB  - The effects of a traumatic neocortical lesions, induced by transcranial cold
      injury, on brain metabolism and gene expression were examined. The surrounding of
      the lesions was characterized by increased glucose and lactate levels without
      major disturbances of protein synthesis or energy state. A transient pH decrease
      by 0.4 units was noticed 1 h post-injury, which shifted towards alkaline values
      by 3 h. The metabolic disturbances did not differ between injured animals with
      spontaneous spreading depressions (SD, n = 14) and those without SD (n = 7). In
      SD animals, c-fos mRNA was strongly elevated in the injury-remote cortex, but
      hsp72 mRNA was not enhanced. Thus, in contrast to focal ischemia, the metabolic
      dysfunction around traumatic cortical lesions is not aggravated by SD.

PMID- 9601704
TI  - Afferent innervation influences HVA Ca2+ current expression in cultured
      neocortical neurones.
AB  - Voltage-activated Ca2+ channels represent a major pathway of Ca2+ entry into
      neurones. The regulation of the expression of functional Ca2+ channels thus plays
      a central role in neuronal differentiation. To study the influence of afferent
      innervation on Ca2+ current expression, we compared HVA Ca2+ currents in two
      categories of cultured neocortical neurones that showed pronounced differences in
      synaptic innervation density. Neurones strongly innervated by a presynaptic
      explant had a two-fold greater HVA Ca2+ current density than neurones not
      innervated by explant fibres. Chronic blockade of synaptic activity did not
      affect HVA Ca2+ current density in innervated neurones. Our results thus suggest
      an activity-independent regulation of HVA Ca2+ current expression by afferent
      innervation.

PMID- 9601705
TI  - [Development of obstetrical analgesia and anesthesia in the Czech Republic].

PMID- 9601706
TI  - [Development of epidural analgesia in obstetrics, a decreased number of
      complications and adverse effects in the mother and child].

PMID- 9601707
TI  - [Overview of methods of obstetrical analgesia used abroad--present status].

PMID- 9601708
TI  - [Errors and omissions in pediatric gynecology].

PMID- 9601709
TI  - [Problems in the diagnosis of congenital developmental defects and disorders of
      the urogenital tract].

PMID- 9601710
TI  - [Problems of young people calling the contraception advice line].

PMID- 9601711
TI  - [Minisiston as a contraceptive for adolescents].

PMID- 9601712
TI  - [Results of contraception counseling in adolescents].

PMID- 9601713
TI  - [Precancerous conditions of the cervix in adolescents and very young women].

PMID- 9601714
TI  - [Perinatology at the crossroads--where to now?].

PMID- 9601715
TI  - [Perinatal care in the Czech Republic from the aspect of care in Sweden].

PMID- 9601716
TI  - [Debatable and negative trends in Czech perinatal medicine].

PMID- 9601717
TI  - [Infection as a cause of premature labor].

PMID- 9601718
TI  - [Fetal hypoxia--an indication for cesarean section].

PMID- 9601719
TI  - [Risk factors in pregnancy].

PMID- 9601720
TI  - [An expectant versus an active approach in post-term pregnancy].

PMID- 9601721
TI  - [Risk in labor induction with prostaglandin E2 administered intracervically].

PMID- 9601722
TI  - [Summary of the thematic section on perinatology].

PMID- 9601723
TI  - [Current trends in prenatal diagnosis and fetal therapy of congenital
      developmental defects and genetic diseases].

PMID- 9601724
TI  - [Screening for congenital defects in pregnancy].

PMID- 9601725
TI  - [Invasive methods of prenatal diagnosis].

PMID- 9601726
TI  - [Ethical aspects of prenatal diagnosis].

PMID- 9601727
TI  - [Diagnosis and therapy of androgenic sterility].

PMID- 9601728
TI  - [New laboratory approaches in fertilization in vitro].

PMID- 9601729
TI  - [Pregnancy after assisted reproduction].

PMID- 9601730
TI  - [The role of the gynecologist in the diagnosis and therapy of breast diseases].

PMID- 9601731
TI  - [Basics of mammography screening in the Czech Republic. Role of breast
      ultrasonography].

PMID- 9601732
TI  - [The Center for Breast Diseases and private practice].

PMID- 9601733
TI  - [The senology program--advantages and pitfalls of team practice].

PMID- 9601734
TI  - [Complications in surgical therapy of breast carcinoma].

PMID- 9601735
TI  - [Early detection, exhaustive diagnosis and initial treatment of breast
      carcinoma].

PMID- 9601736
TI  - [The role of the basal ganglia in control of motor activity].
AB  - Morphological, histochemical and functional analysis of the role of basal ganglia
      in the motor control is presented. The inhibiting effect of basal ganglia on the
      motor activity, their role in programming the slow and stereotyped movements, and
      the presentation of emotional and memory centres to the motor mechanisms of
      behaviour is emphasised.

PMID- 9601737
TI  - [An NMDA glutamate receptor subtype].
AB  - Glutamate is the main excitatory synaptic transmitter between neurones in the
      central nervous system. The excitatory effect of glutamate is due to activation
      of two distinct types of receptor ion channels-AMPA/kainate and NMDA type. This
      article reviews recent discoveries concerning molecular structure of NMDA
      receptor channels, its pharmacology and biophysics including excitatory
      postsynaptic currents mediated by activation of this subtype of glutamate
      receptor.

PMID- 9601738
TI  - [Classification of physico-mechanical mechanisms in primary hypertension].
AB  - Arterial hypertension (AH) is a serious disease with high prevalence in the
      developed countries. In majority of the AH cases, their origin stays unknown
      (primary AH). There is a great number of variants in primary AH illustrating the
      complexity of the disease pathogenesis. We tried out to define a classification
      of primary AH based on the biomechanical mechanisms of elevated blood pressure,
      though we accept that the pathogenesis of AH includes also malfunction of one (or
      more) control mechanism for the initiation of compensation. We have brought some
      examples of unhomologated data in the literature dealing with flow conditions in
      the vascular system. This may explain the underestimation of the role of the
      rheological properties of the blood and the function of precapillary sphincters
      in the ethiopathogenesis of AH.

PMID- 9601739
TI  - [Use of personal computers for simulation experiments in the teaching of
      physiology--methods].
AB  - The paper describes the use of PC in laboratory courses in physiology for the
      simulation of animal experiments or for simulation of behaviour of some
      functional systems of an organism in various experimental situation. It presents
      simple and non expensive system enabling to a large group of students (up to 24)
      to follow simultaneously on their monitors the course and results of the computer
      simulation.

PMID- 9601740
TI  - [Why and how should we teach molecular biology at medical and pharmacy schools].
AB  - Molecular biology becomes an increasingly important topic in the medical and
      pharmaceutical academic education. For many reasons the basic education in
      molecular biology is necessary irrespective of a future orientation of physicians
      and pharmacists. The article seeks to define the limits of molecular biology in
      terms of both the scientific discipline and the teaching topic, and pinpoints the
      main factors and aspects, as well as pitfalls of molecular biological education
      as an integral part of medical and pharmaceutical study.

PMID- 9601741
TI  - [NO-synthase inhibitors and endocrine gland function].
AB  - Nitric oxide is a reactive gas with multiple important physiological and
      pathophysiological effects in the human body. Beside the accepted fact that NO is
      identical with endothelium derived relaxing factor, which mediates the
      acetylcholine induced relaxation of blood vessel wall, important roles of NO in
      the functional modulation of endocrine glands, and in the outbreak and progress
      of experimental diabetes in rats have been proved. The article summarises the
      current knowledge about the action of NO in some endocrine glands with respect to
      the possibility of treatment by means of NO-synthase inhibitors administration.

PMID- 9601742
TI  - [Leptin].
AB  - Leptin (ob-protein), a previously unknown protein signal, is secreted from
      adipose tissue, circulates in the blood, probably bound to a family of binding
      proteins, and acts on central neural networks, that regulate weight and energy
      homeostasis. Leptin provides a communication link between fat tissue and the
      brain. Ob protein appears to play a major role in the control of body fat stores
      through coordinated regulation of feeding behavior, metabolism, autonomic nervous
      system and body energy balance in rodents, primates and humans. Leptin levels
      have pulsative and diurnal character. In lean subjects with relatively low
      adipose tissue, the majority of circulating leptin is in the bound form. On other
      hand, in obese individuals the majority of leptin circulates in free form
      presumably bioactive protein, and thus obese subjects are resistant to free
      leptin. Leptin's resistance is often coupled with insuline resistance
      postreceptor type. Leptin receptor is product of db genes. Ob-protein receptor
      belongs to the cytokine superfamily of receptors and has several variants. Leptin
      receptor gene is expressed in abundant degree in ovary, uterus, testes, less in
      hypothalamus, hypophysis, and little in kidney. Leptin stimulates the
      reproductive endocrine system and may serve as a permissive signal to the
      reproductive system of normal animals. Ob-gene product, leptin is regulated by
      feedings patterns and hormones, such as insulin and glucocorticoids. There is
      assumed that neuropeptide Y (NPY) and melanocyte-stimulating hormone (MSH) and
      its receptor (MCR) are a critical components of the biological response to leptin
      levels. MCR in contrast to leptin receptors are coupled with G-transduction
      system.

PMID- 9601743
TI  - [XXIII National Congress of the Spanish Society for the study of the Liver.
      Madrid, Spain, February 26-28, 1998. Abstracts].

PMID- 9601744
TI  - [Telematics in medicine--developmental perspectives in Bosnia-Herzegovina].

PMID- 9601745
TI  - [Effect of lead acetate on qualitative and quantitative characteristics of
      mammary mast cells in lactating rats].
AB  - The mammary mast cells number, distribution, type and some other structural
      characteristics was studied at 7., 14. and 21. postpartum date in lactating
      Wistar rats receiving deionized water of lead acetate via drinking water during
      the first lactation. Toluidine blue or alcian blue and safranine staining of the
      material from left abdominal mammary glands were used for histological,
      histochemical and morphometry evaluation. Thirty random immersion fields of three
      distant tissue section in the stromal compartment of each gland's areas were
      counted. The fluctuation of mammary mast cells number with peak at 14th
      postpartum date and dominance of granulated and with epithelium unassociated mast
      cells was estimated in normal lactating animals. The parallel progress of
      safranine-positive granules and secretory activity of mammary mast cells with the
      length of lactation was observed in the same group of animals. The fluctuation of
      mammary mast cells number during the lactational period with significant
      increased at 14th postpartum date and dominance with epithelium associated cells
      at the same time was estimated in lead acetate treated lactating animals.
      Safranine-stained positive material was dominant in mammary mast cells under the
      influence of lead. In the same group of animals the progression of release the
      secretory granules from mast cells and partial to total degranulation of cells
      was observed. During the lactation and under the influence of lead the mammary
      mast cells are associated with the gland changes in morphology and function.

PMID- 9601746
TI  - [The effect of duration of endemic nephropathy on serum angiotensin converting
      enzyme activity].
AB  - The effects of duration of disease on serum angiotensin converting enzyme (ACE)
      was measured in 60 patients with endemic nephropathy (30 men and 30 women) of age
      between 30 and 60 years. There were formed three groups: patients with endemic
      nephropathy and duration of disease less than 5 years (n = 23), patients with
      endemic nephropathy and duration of disease between 5-10 years (n = 17); and
      patients with endemic nephropathy and duration of disease 10 years and more (n =
      20). The serum ACE activity was determined by the spectrophotometric method using
      Hip-Gly-Gly as a substrate. The activity of enzyme were expressed in units
      corresponding to 1 nmol of the hippuric acid that was released by the hydrolysis
      of Hip-Gly-Gly per minute and ml of serum. The results showed that serum ACE
      activity decreased in group of patients with endemic nephropathy and duration of
      disease 10 years and more (29.21 +/- 2.25; X +/- SEM) in comparison with group of
      patients with endemic nephropathy and the duration of disease less than 5 years
      (35.57 +/- 1.75), which was statistically significant (p < 0.03).

PMID- 9601747
TI  - [Detection of glomerular basement membrane antibodies using the ELISA enzyme
      assay].
AB  - The intention of this work is to show the usefulness of use of enzymatic essay in
      the anti-body detection against GBM in the serum of the Patient with linear
      deposits of IgG. Full success was obtained. Maximal sensibility of test
      sensibility and reproduction, as well as the advantage that tests are simply
      enough for the empiric application in everyday clinical practice was achieved
      through multiplied vibration of anti-bodies. Test were done 30 patients in the
      Immunology Laboratory of the Institute for Nephrology in Sarajevo.

PMID- 9601748
TI  - [The effect of organization of treatment of injuries on the occurrence of late
      complications of fractures caused by gunshots and explosions in war].
AB  - In this paper we present two approaches we have applied in organization of
      treatment of the wounded persons during the war in Bosnia and Herzegovina, as
      well as later complications. We have analysed 300 wounded persons--150 in group A
      and 150 in group B. They were treated in stage and non-stage form in an urban
      condition. These complications were expected and there were no significant
      difference between these two groups.

PMID- 9601749
TI  - [Aerobic wound infections during the war].
AB  - We presented the results of causative agents of wounds aerobic infections
      obtained during the first three months of third war year in Bosnia. We isolated
      mostly Staphylococcus aureus (54%), Pseudomonas aeruginosa (25%) and Serratia
      marcensens (20%). Other aerobic causative agents of wounds were established in
      less percent. The most frequent infections were detected in swaba specimens
      received from Orthopaedic, Traumathological, Plastical, Vasculary and Clinic for
      Pulmonary Diseases. In discussion we compared our results to data from 1st and
      2nd world war and wars in Algeria, Corea, Vietnam and Israel.

PMID- 9601750
TI  - [Hypertrophic idiopathic subaortic stenosis].
AB  - In 1990 at the Pediatric Clinic in Sarajevo, based upon physical examination EKG,
      RTG and complete ECHO examinations, HISS was diagnosed with a five years-old boy.
      The diagnosis: Stenosis aorte valvularis gr. majoris, Aorta bivelaris, and
      Stenosis r. sinistri ar. pulmonalis have been confirmed by the invasive method.
      The surgical intervention was proposed. Due to war circumstances surgery
      operation was done in Cambridge, in 1993. The child is well now.

PMID- 9601751
TI  - [Occurrence and etiology of tooth caries in wearers of fixed dentures during the
      war].
AB  - Concerning the destruction, war and caries are complemental. They don't have the
      same final causes, but on the microplan, both of them have destruction as a
      consequence. War causes complete destruction of organism, and the crude killing
      of human being. The people who do not get killed are faced to all negative
      etiological factors which disturb general health of organism. We have been
      following the parameter for the need of intervention in the field of dental
      protetic, frequent erosive changes of dental tissues sediments of caries and
      etiological factors which facilitate commencement and development lesions of
      caries on the tooth-carier of fixed protectical work. During this work we have
      been analyzing the patients who have been treated at The Clinic for Dental Health
      during the war in Bosnia and Herzegovina. Etiological factors, that caused
      commencement and development lesions of caries on the tooth-carier of fixed
      protetical work, are identical to those that are described in accessible
      literature, but also there have been some specific features which have been seen
      during the war conditions, as follows: *inadequate nutriment-patients were
      usually eating adhesive food, noodis, *impossibility of maintaining and providing
      the extents of oral hygiene, difficult or impossible access to a hygiene knot,
      *the lack of equipment for maintaining the oral hygiene, toothpaste, toothbrush,
      water, *Fight for the bare life, war is time for survival and it cites patient to
      seiftuiage in care for their own health, patient fights for existence and treats
      the acute states. In this relation brushing the teeth comes to the last place,
      *war conditions unable patients in approaching to therapeuts, and they can not
      use stomatological equipment due to the lack of electric power and water. *time
      as a factor--war circumstances delayed the intervention in the mouth of patient
      at the right time. Percent of sediments of caries inclinical study on the tooth
      carier fixed protetical work is at the high level of 65%. This percentage could
      be justified by a fact that all patients came with already developed lesions of
      caries. War is enemy of human health in every segment, so increasing number of
      lesions of caries is one of the logical consequences. War in BiH has presented
      that stomatological science and practice during war are just curative. Esthetic
      stomatology and right-time interventions, preventions don't exist. There is only
      necessary stomatology.

PMID- 9601752
TI  - [Computer-supported radiologic diagnosis in stomatology].
AB  - In contemporary stomatology practice except routine of using X-rays methods in
      diagnostics of jaws and teeth, the newer methods as computerized tomography,
      magnetotheraphy and radiovisiotheraphy etc. are used. These methods provides the
      physicians doctors easier, faster and cheaper diagnostics of inflammation and
      other processes, and on the other hand, they provide less damages to patients
      [symbol: see text] organism, the basic characteristics and principles of work of
      some of these already mentioned diagnostic methods have been shown in the paper.

PMID- 9601753
TI  - [Medical expert systems].
AB  - Expert systems are software systems that can successfully compare to human
      experts. Their purpose is mostly advisory. Besides, they give explanation and
      advice to human experts when performing certain tasks. They are intelligent
      information systems, and are capable to explain and justify their conclusions.
      Knowledge systems are smaller software systems, and are usually less successful
      than human experts. Main reasons for expert systems development in medicine are:
      need for justification of decisions, need for enhancing performances in many
      uncertain relations; need for explaining of decision making process etc. One of
      the reasons of developing knowledge-based systems was that conventional statistic
      formalisms have not provided satisfactory solutions in medical decision making
      (MDM). Also, today, the relations between cases and conclusions are not
      universally valid. So, few causes can provide the same conclusion. Besides, data
      are not necessarily absolutely accurate. The area of applying expert systems is
      very wide: diagnosis, prognosis, self-education, directing etc. Basic structure
      of expert system consists of: knowledge, data base, inferring mechanism,
      explaining mechanism and user-interface. Though, expert systems also have certain
      bad features: primarily, they are not physicians i.e. they can not examine a
      patient. Furthermore, expert system that is good for one certain area is often
      not good for another one. There are some cases, when these systems can confuse a
      physician and make him to make a wrong decision. This occurs very often in two
      specific cases: when the clinical situation is urgent; and when accuracy of
      clinical information is not definite.

PMID- 9601754
TI  - [95 years' of radiology in Sarajevo].
AB  - The development of the radiology in Sarajevo from its beginning in "Zemaljska
      bolnica", 3-4 years after Rontgen's epochal finding of X-rays, till now has been
      reviewed in this paper. Equal and parallel development of the diagnostic
      radiology, as well as radiotherapy is given chronologically, regarding the stuff,
      equipment and premises. This is referred to the period before and after The
      Second World War till 1973, when--after stagnation--radiology started developing
      relatively quickly. With the integration of the service within the Sarajevo
      Region, building the annex, modernizing the equipment, especially by providing
      digital radiological techniques, current organisation of the work and necessary,
      adequately educated medical stuff, the development of radiology in Sarajevo was
      on its way up, in professional, educational and scientific aspect. At the end,
      present condition and the needs of premise, equipment and stuff, as well as some
      points of the possible further development of the radiology in Sarajevo have been
      summarized in this paper.

PMID- 9601755
TI  - [History of the neuropsychiatric health service in Bosnia-Herzegovina].
AB  - During the Turkish rule, there was no organized medical protection of population,
      and the mentally ill people have been in especially difficult circumstances,
      since not a single institution has existed before 1640, when in Sinan [symbol:
      see text]s Tekija in Sarajevo some kind of haven for mental patients was
      established. More severe cases were sent to the uncertainty of Hospital for
      Mentally ill in Jedren, deep in the heart of Turkish Empire. Mental patients of
      Christian religion were treated in churches, monasteries. The Francistiens Order,
      that has been active in the region since 13th century, was especially involved.
      After occupying Bosnia and Herzegovina, Austro-Hungarian Monarchy found only
      "Vakuf Hospital" and Turkish Military Hospital, in 1866. After establishing state
      Hospital, ex "Vakuf Hospital" was turned into the first Psychiatric institution,
      which was conducted by Health Counselor, dr Carly Bayer. In 1908, he became the
      first Head of newly-built Department for mentally ill persons within the State
      Hospital. By the end of the First World War, there was 113 beds and one doctor in
      change, Chief of staff dr Egon Zahratka, who was succeeded by dr Salvator
      Karabaji. In 1947, Neuro-Psychiatric Clinic within the Medical Department of
      Sarajevo University was established, and its founder and the first Head was prof.
      dr Nedo Zec. One year later, a Psychiatric Hospital was opened in Jagomir, in
      vicinity of Sarajevo. Since then neuropsychiatric health services have been
      constantly expanding, and that is shown in the tables within the paper.
      Independent development of neurology, psychiatry, psycho-therapy, pharmacological
      biological psychiatry and other branches enabled foundation of independent
      specialized psychiatric and neurological institutions. The expansion of
      scientific research and educational activities was direct consequence of that.
      This expansion has been extremely successful during last several decades, that
      the experts from our Republic were very highly appreciated within the former
      Yugoslavia, as well as abroad.

PMID- 9601756
TI  - [The future of medical education in Bosnia-Herzegovina].

PMID- 9601757
TI  - [Culture of endothelial cells as an in vitro model for experimental and clinical
      research].
AB  - Culture of endothelial cell is gotten from human umbilical cord by enzymatic
      digestion. For the growth of cells in culture, medial RPMI 1640 with 20% mixed
      human serum (NHS) or 20% fetal calf serum (FCS), endothelial cell growth factor
      (ECGF) and heparin have been used. Plastic, 0.1% gelatin and fibronectin have
      been used as a fundament. Immune identification of endothelial cells was culture
      is performed by monoclonal antibodies on vWF:Ag. Homogeneous cell line in culture
      might be used as in vitro model in both experimental and practice work.

PMID- 9601758
TI  - [Serum angiotensin converting enzyme activity in patients with untreated
      essential arterial hypertension].
AB  - The serum angiotensin converting enzyme (ACE) in 30 patients with untreated
      essential arterial hypertension, 30 patients with chronic renal failure
      accompanied with arterial hypertension and 30 healthy individuals was measured.
      The subjects of both sexes have been old 35-60 years. The serum ACE activity was
      determined by the spectrophotometric method, using Hip-Gly-Gly as a substrate.
      The serum ACE activity significantly increased in patients with arterial
      hypertension (32.48 +/- 2.02; X +/- SEM) and patients with chronical renal
      failure accompanied with arterial hypertension (37.10 +/- 1.45) when compared to
      the healthy individuals (20.83 +/- 1.33). Possible mechanisms of increasing ACE
      activity with the patients suffering of arterial hypertension are discussed.

PMID- 9601759
TI  - [A controlled clinical trial of methylprednisolone in patients with the
      cholestatic form of alcoholic liver cirrhosis].
AB  - Fourty patients with alcoholic liver cirrhosis and refractory hyperbilirubinaemia
      were included in a prospective, double blind, comparative trial. Twenty of them
      were randomized to methylprednisolone (1 mg/kg/day i.m. over 3 days), and 20 to
      placebo (saline) of identical shape. In the active group a significant decrease
      in the bilirubin level (from 248 to 191 mumol/l, a drop by 23%; p < 0.05) was
      observed, which was not the case in the control group (from 292 to 300 mumol/l,
      an increase by 2.7%; p > 0.05). A decrease in the alkaline phosphatase activity
      was observed in both groups (by 11% in the active and by 20% in the control
      group: p < 0.05) while the encephalopathic indices did not improve in either. It
      is concluded that a short course of corticosteroid could speed-up the hospital
      stay and possibly slow down the progression of alcoholic cirrhosis.

PMID- 9601760
TI  - [Clinical and histologic findings in patients with renal amyloidosis].
AB  - Renal amyloidosis is a rare disease when compared to other kidney diseases.
      During the period of last fifteen years, at the Institute of Nephrology and
      Immunology in Sarajevo renal amyloidosis was diagnosed with 15 patients. The
      disease occurred more often with men than with women. Only during 1988, renal
      amyloidosis was revealed and followed up with five patients. The most common
      clinical manifestations of renal amyloidosis are nephrotic syndrome and chronic
      renal failure, with respective laboratory findings. Using immunofluorescent
      analysis of the kidney biopsy material, we discovered deposits of immunoglobulins
      of different intensity and deposits of lambda and kappa light chains of
      immunoglobulins. The intensity of lambda light chains is greater than that of
      kappa chains. The analysis of light microscopy showed nodular mesangial deposits
      and deposits along GBM without proliferation. The diagnosis of amyloidosis was
      confirmed by staining of amyloid. Application of therapy for amyloidosis was
      without any effect. Although renal amyloidosis is a rare disease, we want to
      point out disease as being an etiologic factor in nephrotic syndrome.

PMID- 9601761
TI  - [Serologic verification of epidemic hemorrhagic fever during the lifting of the
      blockade in Sarajevo].
AB  - OBJECTIVES: After four years of Sarajevo siege, the deblocade started on July
      1995. Many soldiers involved in the deblocade developed a clinical symptoms of
      hemorrhagic fever indicating a possible epidemic. METHODS: Suspected patients
      were treated in the war hospital Igman-Fojnica. Blood samples of all the patients
      were processed on IgM and IgG antibodies with ELISA test, using "the double
      sandwich" technique. RESULTS: IgM and IgG were performed on Puumala (PVV),
      Hantaan (HTN) and Dobrava antigens. 38 out of 45 treated serums had high antibody
      titres. Sera of 28 patients had high titres of specific IgM antibodies on Hantaan
      antigen (12,800). A ten patients had a same titre level for specific antibodies
      of Puumala antigen. A 20 patients had specific IgG antibodies on Dobrava antigen
      with the titre 400. Our results confirmed the epidemic for which were responsible
      two serotypes of HFRS-PVV and HTN. They also proved the existence of a new
      serotypes appearing for the first time in Sarajevo region. This epidemic confirms
      that BiH especially Sarajevo region are among the biggest epidemic areas of HFRS
      in Europa.

PMID- 9601762
TI  - [Comparison of the major cardio-rheumatologic diseases at the Pediatric Clinic
      before and during the war].
AB  - This article presented the analysis of structure of morbidity of
      cardiorheumatological diseases at Pediatric's Clinic Sarajevo, before and during
      the war. The results showed that number of acquired heart diseases has not
      decreased, with permanent presence of streptococci.

PMID- 9601763
TI  - [Diagnosis of duplicate superior vena cava].
AB  - Anomalies of the system vein entrance into the right atrium are rarity,
      particularly in the double superior vena cava. As an isolated anomaly it is
      asymptomatic. Throughout eight years period we have been making computed
      tomography checks of 4045 patients, and with five of them, meaning 1.2 promil we
      have discovered double superior vena cava as a random finding. The diagnosis was
      confirmed by means of a bi-cubital intravenous digital subtraction angiography.
      The diagnosis of these anomaly is significant for the differential diagnostics
      from tumor syndrome, as well as for prevention of surprises in studies of the
      mediastinum.

PMID- 9601764
TI  - [Canine teeth as an experimental model for fixed stomatologic prosthesis].
AB  - Clinical researches, especially pathological-histological experimental researches
      in mouth of patient reach the level of impossible, from the ethical and law
      aspect. Trying to define particular state concerning relation of fixed protetical
      work in the mouth of patient to tooth caries and surrounding belonging tissues,
      there is a question whether it is necessary to establish milieu-in vivo--which
      follows scientifically established principles. These principles are necessary for
      converting results which would become valid in scientific defining of state in
      the mouth of patient, as well as on the tissues which we want to research
      clinically and experimentally. Experimental animals are the second choice for
      researching tissues of human beings. Dogs have many conveniences that classify
      them into most usually experimental animal.

PMID- 9601765
TI  - [The relaxed mucoperiosteal flap in treatment of alveolar extension cyst].
AB  - Justification of the relaxed mucoperiosteous flap application is proved by
      clinical investigation. Faster creation of a somewhat more significant layer of
      the newly created bone as well as the shortening of the post-operational clinical
      in relation to the open and closed operational method are due to the fact that
      this method was carried out by the principle of closed operations which ensure
      the healing of the wound per primam intentionem. Equally distributed, not too
      voluminous blood clot, enabled its faster resorption and organization, acting
      stimulatively on quickened osteogens, regenerational and reparational post
      operation processes.

PMID- 9601766
TI  - Medical informatics--an interdisciplinary approach.
AB  - Medical informatics is the first science that has incorporated all traditional
      medical disciplines. That progress is possible due to fast development of new
      technologies, particularly in informatics, as well as due to common needs of all
      medical disciplines. Information is crucial component of all investigations, and
      that is why the main goal should be incorporation of information technologies
      into medical practice. Due to its complexity, medical informatics is
      interdisciplinary. That is evident through incorporation of different methods,
      principles, techniques etc., that are used while carrying out the tasks in the
      field of medical informatics. Implementation of modern technologies, particularly
      information technologies in medicine, will enable faster data processing; it will
      reduce expenditures in all branches of medicine (statistics, documentation or
      documentary etc.). Thus, medical staff will have much more time to devote
      themselves to primary tasks.

PMID- 9601767
TI  - [Philosophy of life and human health].
AB  - In order for people to survive on the Earth, they have to learn to live one with
      others again. The time when our future was simply given to us has already passed.
      We have to reach our future again, and to become "the farmers of the time".
      Appropriate life style is without any doubt the crucial factor in people [symbol:
      see text] s health protection. Beside high-quality medicine and its movement to
      health prevention, (and not just taking care of illness) human beings need to
      know how to live. This is important because it is in the range of our own
      possibilities and willings. Sooner or later, we will have to be aware of that.

PMID- 9601768
TI  - [50 years' of continuing medical education in Sarajevo].
AB  - This year it has been 50 years since the Medical Faculty in Sarajevo was founded.
      Half a century in existence of a scientific and educational institution
      represents a period which is sufficient to make a serious retrospective, but also
      to make a serious analysis and projections for the future. Medical Faculty in
      Sarajevo was therefore been opened in 1944. There were students in the first
      generation, who completed the educational process from the first year program of
      studies. Due to circumstances of war this process at the Faculty was interrupted.
      On November 16, 1946. Medical Faculty in Sarajevo was reopened and since then it
      has been continuously working for 50 years, maintaining its educational,
      scientific and health activities. Former departments of the General Hospital in
      Sarajevo have grown into its clinical departments and during the period between
      1947 until 1952, the majority of its institutes have been already constructed.
      The development of some of the clinics was however a little bit slower. Within
      the educational process we can separate four stages in the development of the
      Faculty; period from 1954 which has been characterized by a classical middle
      european educational plan and program; from 1954-1956, the so-called "block
      system" of monocourse educational process; in the period 1956-1990, a five years
      study curriculum has been promoted with attempts to reform the educational
      process; from 1990 until today, the six-years study curriculum has been
      introduced, being in accordance with the plans and programs of European
      educational institutions. There were 14,000 students who have throughout this
      period been enrolled in Medical Faculty in Sarajevo, and 6575 have successfully
      completed their academic curriculum and obtained the title doctor of medicine.
      The Faculty has also preserved the continuity of its work under the circumstances
      of aggression and blockade of Sarajevo. Educational process was maintained
      without interruptions applying the methods adapted for the circumstances of war,
      which nevertheless assume full study plans and programs. The results of this work
      were 164 graduated doctors of medicine, 21 masters of medical sciences, and 17
      successfully defended doctoral theses. The Faculty is presently involved in
      reralization of 15 scientific-research projects with a dominant war-related
      issues investigates. The Faculty organized or sponsored 9 scientific meetings.
      The contribution of its professors and assistants, but also of its students was
      invaluable in this war, some of whom have sacrificed their lives, and some of
      whom were seriously wounded and remained disabled in their strive to maintain the
      principles and ethics of their profession.

PMID- 9601769
TI  - [Emergency medicine in Bosnia-Herzegovina].

PMID- 9601770
TI  - [Emergency medical care--an important factor in prehospital emergency medicine].
AB  - When looking at Emergency Medical Service as an example of emergency medicine in
      BiH, the authors present the following concept: that the management of medical
      emergencies in the prehospital phase of medical emergencies is the responsibility
      of EMS. The modern conception of EMS is examined in a comprehensive fashion,
      exploring the evolution of the discipline from its inception to the present, the
      conditions necessary for the EMS to function effectively (equipment, education
      and organisation), and examples are cited from foreign countries demonstrating
      the best results in the field of emergency medicine. The recommendations for EMS
      in BiH are made based upon the original conception of emergency service, with
      significant influence from US and German systems respectively. The article makes
      the case for EMS to be the only provider of prehospital medical care, and
      examines possibilities for further improvements in organisational structures, and
      the conclusions drawn reflect the fact that EMS is the institution capable (and
      responsible) for health care in prehospital phase of medical emergencies. This is
      found to be a rational assessment of the countries needs within the context of
      actual capacities.

PMID- 9601771
TI  - [Activity, organization and experience of the emergency service in Gorazde from
      May 1992 until the signing of the Dayton Peace Agreement].
AB  - Good organisation of health protection wards is an essential precondition for a
      quick and efficient health service. The beginning of the aggression in Bosnia and
      Herzegovina and Gorazde itself in May 1992 brings Gorazde under siege preventing
      supply of any movement of people as well as medical material, equipment and
      staff, especially surgeons. Under such conditions the whole activity is carried
      out in the Emergency Ward and it becomes reception, triage and reanimation ward
      of the War Hospital with an organised part for operations of the patients (4-6
      beds). The work is organised in teams of two doctors; two nurses and one
      assistant with constant engagement of lab, X-ray diagnostics, transfusion service
      and when the conditions for it were fulfilled also the consultancy of surgeons.
      According to data from the doctor's protocol in this ward from 4, May 1992 to 31,
      December 1992 there were 49,285 patients among which 4,771 or 9.67% were wounded.
      Also from the protocol of operations it is clear that from 21 September, 1992 the
      number of 712 wounded were operated or 14.9% of the total number of wounded
      people. From these informations we see that among 16 wounded that came to this
      ward on daily basis 15 of them were treated in this ward and 1 was sent to the
      operation theatre. Except from normal activities the doctors in this ward were
      engaged as court experts, visited the prison, teachers in first aid training and
      self-aid of civilians and members of the Army and at the periods of aggressors
      offensives they were treating all sick people because other wards were not
      working. Thanks to well organised activity and professionalism of the workers a
      great number of patients were treated, a great number of the badly wounded were
      prepared for the operation theatre. In that manner the work of surgeons was much
      easier and better results of the treatment were achieved.

PMID- 9601772
TI  - [Care of the injured in the prehospital phase--experience of the emergency
      medical service in Tesanj from May 1992 to the time of the Dayton Agreement].
AB  - In the introduction are given the basic remarks about the significance of the
      phased medical treatment of the injured persons. Developing the problems, the
      focus is intended on the first phase-pre hospitalised treatment. In the first
      years of the war the percentage of 19% of the injured persons medically treated,
      18% treated by co-fighters and neighbours as well as 9.3% of those who were
      treated by themselves is not encouraging. This relation was being changed during
      the war, but in a total depiction, taking into consideration the war years in
      global, there had always been a lot of the "self-picked up". Most of the wounded
      people would have been alive, if they had been offered by the adequate medical
      care on time in the pre-hospitalised phase.

PMID- 9601773
TI  - [Importance of beginning prompt cardiopulmonary resuscitation as a factor in
      survival in emergency medical care].
AB  - The article presents an overview of 14 months of operational experience in
      prehospital cardiopulmonary resuscitation and the data collected during this
      period from the RMS Centre, Sarajevo. Between June 1996 and August 1997, the EMS
      teams dispatched from EMS Centre resuscitated 106 cases of non-traumatic
      respiratory and cardiac arrest. The data includes analyses of the reasons for
      this vital stoppage, employing standard measures for classifying each case. From
      the total number of cases studied, 18 patients were successfully resuscitated
      (16.98%), and with spontaneous respiration and circulation, were transported to
      the emergency room, but only six patients were released from the hospital after
      definite treatment (5.66%). The conclusions drawn from the study indicate that
      CPR is the most critical factor in the successful prehospital resuscitation of
      cardiac arrest victims, and that educated non-professionals can play an important
      role in life-saving during the critical period prior to the arrival of EMS
      providers. More work on this topic (i.e. Community education and information) is
      clearly needed in order to better understand the practical implications of this
      assertion.

PMID- 9601774
TI  - [Personal experience in the organization of mass admission of traumatized
      refugees].
AB  - Here is showed experience and importance of Emergency Medical Service during mass
      reception of traumatised displaced persons from Srebrenica in July 1995. During
      organisation of reception a good willingness and experience of this service with
      repard a to fast action, examination and selection of more than 15,000 displaced
      persons. In short time, whole coming persons were examined; medicine treated and
      in other way cared. There were arranged, 234 doctor teams, 22 stomatologist
      teams, 42 laboratory teams, 42 hygiene-epidemiologist teams and 18 teams for
      vaccination of children. In the various pathology of coming displaced persons
      there were dominated: respiratory disease case and uncared skin infections in
      children, chronical cardiovascular disease and malnutrition in adults. For
      successful realisation of this complex tasks, like the organising of reception
      and medical care of huge number of traumatised displaced persons, it is needed to
      have well organised, qualified and technical equipped Emergency medical Service.

PMID- 9601775
TI  - [Financial expenditures in emergency medical services and its funding].
AB  - The experience gives us a suggestion of how to solve the problem: the urgent
      medical care is an obligatory aspect of the health protection, it is being
      offered to everybody, the expenses of medical treatments are delivered in favour
      of the injured-taken ill persons, medical personnel cannot have the authority to
      determine the offenders in the accidents and fights, after offering the urgent
      medical care there should be a written report about medical expenses along with
      the police finding through the service of institution, the expenses for the
      unsecured person should be paid from the municipal funds, the expenses of the
      medical treatments for the foreigners with a security number should be
      compensated from the beneficiaries or from the cantonal or federal budgets.

PMID- 9601776
TI  - [Experience of the Center for Emergency Medicine of the University Medical Center
      in Sarajevo and principles of the emergency medical care system].
AB  - In siege and blocked Sarajevo, in 40 months, in primary care unit and than in
      Emergency Department 42,075 injured and ill persons have got the first aid. Out
      of that, 37% were injures 16% acute surgical conditions, 23% internal urgent
      conditions (since October 1994). There were 24% non-urgent cases from the
      surgical field. In this period of time 107,453 patients were treated hospitably,
      with an average of 2.108 hospital beds. In 1996, the primary care was given in
      21,708 urgent cases, or 60% of 36,312 hospitably treated persons in total. There
      were 29% injuries, 24% of acute surgical cases, and 47% of internal medicine
      cases. Urgent centre received 53% individual paints who came by themselves
      without any medical aid; 25% from health centres where they have bog a primary
      care, and 22% came after received first aid of primary care in the Emergency
      department. By applying war surgical doctrine and general medical doctrine, with
      appropriate services for prompt diagnostics and treatment, with qualified
      specialists and consultancy services, a good quality of adequate treatment and
      care has been achieved, the mortality has been reduced, the hospitalisation has
      been rationalised, and treatment length has been reduced. Analysis demonstrates
      the reasons for existence of such medical centres in large hospitals. We have
      recognised the problems we are facing with, and which have to be solved
      progressively, as well as those concerning the functioning health services in
      Sarajevo Canton, and Federation of B&H. On the basis of all these knowledge's we
      believe that a well organised urgent medicine implemented in practice has great
      importance in the overall treatment. Basic objectives for establishing the urgent
      medicine as a system are: The first priority is to organise a modern system of
      urgent medicine, based on the principles of general medical doctrine and
      complementing with health care system. Urgent medicine programme should be
      incorporated in the process of medical education of the medical staff, giving a
      priority to the activities in practice. Provide modern equipment and adequate
      working space. Develop already developed co-operation with institutions and
      professionals from Europe and USA. Improve the low level of the first aid
      training of the population through the first aid courses.

PMID- 9601777
TI  - [Organization of emergency medicine in hospital health care].
AB  - Emergency Department of Zenica Canton Hospital, from its beginning of the
      existence dated on February 1, 1994, is trying to implement within its work the
      following basic issues of urgent medicine: continued education in a field of
      treatment life threatening diseases and injures; co-operation with different
      medical specialists; human and unselfish care of patients; widely open readiness
      for perception of new knowledge's and giving support in the education of other
      people. Thanks to the supervision of doctors from USA, Australia and Canada,
      which lasted from February 1, 1994 until September 30, 1997, Emergency Department
      stuff members, managed to go over beginning birth difficulties of this
      Department, followed by continued education and implementation of basic
      organisation issues. Work organisation is based on receiving of the patients,
      treatment of life threatening diseases. Triage of patients depending on the
      cause, co-ordination with different medical specialists with the purpose of final
      treatment, as well as the education of stuff members in particular separated
      spaces such as: reanimation room, surgery room, paediatric room, receiving room,
      observation room and education room at the end (slides). During the wartime ED
      affectedly infected on other departments in a field of primary treatment of the
      patients, adequate triage, preparation of the patient for the surgery, as well as
      in the observation of cold and unclear cases. Statistics of treated patients
      during six months time period in 1995 and 1996 shows the increase of the number
      of patients with final treatment ED and almost equal number of surgery and
      internal cases (graphic presentation). Problematic of ED has its own specifics,
      which needs to be presented in special way (graphic presentation).

PMID- 9601778
TI  - [Emergency medicine in hospital practice--personal experience and suggestions].
AB  - In this work are presented experiences concerning the surgical services of
      General hospital in Konjic and ill people during the conditions of war. There
      have been described organizing principles and ways of connecting urgent service
      with hospital services.

PMID- 9601779
TI  - [Treatment of emergency conditions in the aged--suggestions for solutions].
AB  - If it is true that we are living in the era of sure surgery and dangerous
      medications, then this fact is particularly relevant in the treatment of elderly
      patients from third age-group. The uncontrollable growth of the number of such
      people (demographic signs point to an increase of population by 100%), demands
      complete changes in the medical approach to patients from the third age-group,
      especially considering the peculiarities of the geriatric medicine: intermingling
      of involute molecular ageing changes; multimorbidity; especially chronic
      development of decease; changes in the selection of selection of appropriate
      medications and medical treatment. Problem of chronic illness is the most
      outstanding problem of old age, and therefore, within the total health-care
      system nothing can be right, nor in its place, until major questions of the
      health protection for elderly in the third age-group are resolved. One of the
      most important phenomenon associated with these problems is in hospitalisation
      where, because of a limited hospital capacity, there is usually not enough space
      for patients from middle age-group, and even more so for elderly from the third
      age-group. According to presented data, the fact that third-age group constitutes
      23.11% of examined patients, points to an obvious urgency and the actuality of
      these matters. The health problems of patients from third age-group demand
      special training of physicians and their assistants of all profiles, and a
      special scientific research in this area.

PMID- 9601780
TI  - [Importance of emergency protocols in reconstruction of the foot after injury by
      land mines].
AB  - In this paper the author gives his first experience after using pre-hospital
      protocol for treatment of wounds after step on land mines. There were 20 patients
      with isolated injured foot. After hospital (surgical) treatment it was seen low
      incidence of complications.

PMID- 9601781
TI  - [Acute states in poisoning with corrosive substances].
AB  - Caustics are products which produces necrosis on contact place with chemical
      affinity to organic substance. Destroying intensity depend of types,
      concentration and quantity of product ingested. Poisons could be accidental and
      suicidal. Concentrated caustics rapidly produces necrosis, strong pain and severe
      general reaction on acute trauma, shock. Except the fact that acute burns with
      caustics products require an immediate diagnostic and therapeutic approach, this
      problem remains controversial. A retrospective analysis of 97 cases in last five
      years, including the war, in our ENT clinic done. Sex, age types and frequency of
      product ingested. Accidental, suicidal and the most often month it is happened
      analyzed. The acute diagnostic procedure in caustics ingestion are primarily
      directed toward the recognition of life-threatening complication such as shock,
      airway obstruction, perforation of inner organs and in severe acid ingestion,
      metabolic acidosis. esophagoscopy and endoscopy is accurate in predicting degree
      of esophageal injury. The aim of therapeutic procedures is to preserve
      homeostatic balance, to prevent shock and complication of acute hemorrhage or
      perforations as well as in the development of scar tissue and nepotistic
      strictures over time. The aim is to preserve the patients own esophagus. During
      long time experience treatment with diet, cortisone, antibiotics was successful
      in the prevention in the development of scar tissue and neoplastic strictures
      over time from esophageal II and III grade lesions.

PMID- 9601782
TI  - [First aid and initial medical care in injuries of the large blood vessels].
AB  - Nowhere as in emergency medicine results of a well done first aid can be more
      obvious as in the cases of big blood vessels injuries. Properly done first aid
      and first medical aid at big blood vessels injuries save the life of the patient.
      The following example is the case of MM patient The patient was received in the
      Emergency ward after an explosive injury of the big artery vessels and badly done
      first aid and be was without any signs of life. The patient was treated with:
      Adrenalin hydrochloride 1 ml intracardial Hydrocortisone amp a 1000 mg i.v. Sol
      Haemaccel 3 x 500, o ml i.v. Sol Hartman 3 x 500 ml i.v. Na-bicarbonate amp a 40
      mg i.v. (2 x 20 mg) 9 bottles of fresh blood (300 ml each) After the intensive
      cardiopulmonal reanimation the patient after 3 hours he was in a stable general
      condition and sent to the operation theatre. For proper first aid the methods and
      activities are very simple but they should be known and implemented. In the
      opposite case a patient can lose all the blood and die in a hemorrhagic state.

PMID- 9601783
TI  - [Legal regulation of emergency medicine in Bosnia-Herzegovina and practice of
      emergency medical care in Sarajevo].
AB  - In preface chapter is signified necessity of doctrinaire stations changes
      considering the position and the role of emergency medicine in the health care
      system and especially in emergency medicine practice. Principles and determinants
      of emergency medicine organisation in out legal regulation that are described,
      with emphasised positive experiences reached throughout consolidation and
      modernization of organisation and practice of the Emergency Medical Service
      Centre Sarajevo, are given according to the real needs of the human society. Some
      of the characteristics of the medical staff potential, educative qualifications
      and medical-technical potential of the ambulance vehicles are also propound.
      Finally are proposed measures and procedures for improvement of health care
      system regarding emergency service as framework for effective application of
      contemporary scientific achievements in this field.

PMID- 9601784
TI  - [Health care reform in Bosnia-Herzegovina and reorganization of emergency medical
      services].
AB  - The reform of the constitution of Bosnia and Hercegovina would be incomplete if
      it did not have the reform of the emergency conditions. The Ministry of health of
      Bosnia and Hercegovina is determined to complete reorganization of the emergency
      health services. The principles and models of this reorganization are based upon
      the experiences before and during the war, but they are also based upon the
      experiences we shared with another countries in Europe and in the world.
      Reorganization is to be done with the degree of responsibility considering the
      importance of the matter. In this work there principles and factors which are
      determinators for the quality and efficiency of these services. The definition of
      standards and instruments of evaluation are suggested so that the higher
      institutions could watch over the efficiency of these services.

PMID- 9601785
TI  - [Organization of emergency medicine based on the frequency and severity of
      emergency conditions].
AB  - The spontaneous development of the organization and practice of emergency
      medicine created a number of types of emergency medicine units. Long time, these
      units were developed in out-hospital institutions such as health centres.
      Together with these services, all acute hospitals have had full day,s emergency
      services for definite care of urgent conditions. The authors give principles of
      this activity organization in the light of expected incidence and severity of
      urgent conditions related to the number of population which gravitate to
      particular hospital or other health services. Starting from the assumption that
      expected frequency of urgent conditions per 100 persons in 24 hours is between
      0.50-0.75, the authors present the model of health care organization of such
      cases including family doctor, health station, health centre, hospital.

PMID- 9601787
TI  - [Organization of emergency medical care in the United States of America].
AB  - Organised emergency medical services in the United States are a relatively recent
      development. Prior to 1967, emergency medicine was uncoordinated, inefficient and
      frequently of poor overall quality. Patients were transported to the hospital by
      ambulances that in a many cases were owned by funeral homes. Funeral homes had
      vehicles that were able to accommodate a stretcher but were not configured for
      ongoing patient care. Ambulance attendants had little training beyond basic first
      aid. Hospital care was not much better. Patients were usually taken to the
      closest facility regardless of the capabilities of the hospital. The doctor on
      duty usually had no formal training in emergency medicine. In many cases, the
      doctor was assigned as the "on-call" doctor for the day and did not work full
      time in the department. One day might find practitioner on duty, the next a
      psychiatrist or pathologist providing care during the critical early hours of a
      serious illness or injury.

PMID- 9601786
TI  - German rescue system--an overview.
AB  - Aim of the report is to show the structure, organisation and legal aspects of the
      rescue system of the Federal Republic of Germany. The laws are the basis of the
      rescue system in each of the sixteen federal countries. The governments of the
      countries delegate their tasks to the administrative districts. Several
      organisations like German Red Cross, the Fire Brigades; societies like Arbaite
      Samariter-Bund, Johanniter-Unfall-Hilfe, Malteser-Hilfsdienst take part in the
      rescue system with a great number of paid professional people and volunteers with
      a more or less professional education. Who is Who in the rescue system? Who is
      responsible for medical education and what is the difference between the rescue
      system and the "doctor on emergency call"? Both systems exist side by side, but
      they are very different from one another. The "doctor on emergency call" is
      private organised by the board of general practitioners and is responsible for
      "all day" emergency cases on weekends and during the night. The task of the
      countries and districts is to care for the rescue services, and they should only
      be used for severe injuries and illness. Most of the physicians taking part in
      the rescue services belong to hospitals and have no financial interests in their
      duty.

PMID- 9601788
TI  - Development of education emergency medical staff in Sarajevo during period 1996.
      1997.
AB  - The author gives out his experiences in EMS training in Sarajevo under the
      leadership of Johanniter-Unfall Hilfe, Hannover, Germany and also gives his
      suggestions for corporation of all Emergency Wards in Bosnia and Hercegovina.
      During the work there was a comparison for the experiences of the organisation of
      EM in North and Middle America.

PMID- 9601789
TI  - [Medicinski Arhiv--MEDLINE--Internet].

PMID- 9601790
TI  - [Morphometric aspects of ultrastructural details of rat thyrocytes which have
      been irradiated and pretreated with melatonin].
AB  - In this work the authors investigated by qualitative and quantitative analysis of
      ultrastructural details of thyreocytes in irradiated rats with and without of
      melatonin treatment. On the basis histological qualitative and stereological
      analysis of materials and by the comparison of results in the animals who
      received and who didn't receive melatonin before irradiation it can conclude that
      melatonin modifies behaviour the thyroid glands in irradiation stress.

PMID- 9601791
TI  - [Cardiovascular response to the treadmill exercise test in young women in
      Sarajevo during chronic stress due to the war].
AB  - This study is unique in its approach because it was carried out under extremely
      hard conditions during intensive war activities. Specific characteristic of this
      aggressive war was that civilian population was forced to live in war zone for a
      very long period without enough food, water and energy supplies. It was really
      stressful to live with cognitiori that anyone at any moment and place could
      become victim of sudden shelling and shooting of civil targets. The aim of this
      study was to assess how the war caused stress influenced the function of
      cardiovascular system and its response on stress exercise in young women. The
      subjects were selected among the students of Sarajevo University. All of them
      lived in Sarajevo during whole war period. Nine young women (age 18-21) performed
      multistage incremental exercise treadmill testing under Bruce protocol. It was
      planned for each subject to complete two exercise sessions in three months
      interval, but only five persons completed second session. It was a period of
      intensive attack on the city so that some of our subjects left Sarajevo and some
      were wounded. The results of two exercise sessions showed that resting values of
      cardiovascular variables, were within physiological range but with great
      individual variations. The mean maximal exercise capacity expressed as metabolic
      units (METS) was 13.67 +/- 1.00 for the first exercise session and 13.40 +/- 0.89
      for the second. Heart rate in response to exercise increased rapidly. It was
      achieved about 95% of predicted max. There were no significant differences in the
      results of two exercise sessions. Hyperreactive physiological responses as
      consequences of war caused stress could not be changed in so short period and
      under unchanged war conditions.

PMID- 9601792
TI  - [Diagnosis of post-traumatic aortic pseudoaneurysm].
AB  - We can say that with the traffic's development, more and more, we become faced
      with aorta's posttraumatic pseudoaneurysm. We diagnosed it, accidentally, in the
      medical findings, with five patient, by computed tomography, and intravenous
      digital subtraction angiography, within the thirteen years period. These methods
      are presented as complementary ones in the matters of diagnose. Diagnose is of
      the great importance for this disease, considering its unpredictable evolution
      and a possibility of death outcome.

PMID- 9601793
TI  - [Gluten enteropathy].
AB  - In this case report has been shown 32-old women patient. She was received on
      Department of Internal medicine of State Hospital "Sarajevo" because of
      prostration, weight loss (more than 20 kg) and frequently, abundant diarrheas.
      Clinical treatment, including biopsy of small intestine, referred on gluten
      enteropathy. In war-stricken Sarajevo, when major part of food were bread,
      macaroni and pies, obviously there was perception of sensibility on gluten in
      this women who hadn't got any similar problem for her life. After adequate diet
      without gluten, on the control examination two month later, we can hardly
      recognize our patient. She can get more than 20 kg, without mental depression and
      would be married soon.

PMID- 9601794
TI  - [Wilm's tumor in a 3-year-old boy].
AB  - We report a case of 3,5 year-old boy with tumor of the left kidney which
      presented metastatica changes in upper stomach and in the lungs. After performed
      nephrecomy and confirmed P-H diagnosis: Tu-Wilms, intensive chemo and
      radiotherapy was started according brand new protocol UKW3. Therapy was performed
      partially in Liverpool (UK) and final part at our hospital. Now, there are no
      signs of disease in patient and according prognostic criteria he has a good
      chance of cure.

PMID- 9601795
TI  - [The value of horizontal discrepancy on the subgingival position of the tooth
      crown].
AB  - Marginal adaptation of the crown edge has been considered as primary and
      significant factor of prevention of secondary caries and periodontal disease on
      carryig tooth. There has been a clear dependence between hunting the periodontal
      tissue and the quality of edge closing of the crown. If we position subgingivaly
      the crown which clinically shows a good adoptiveness marginally and at the same
      time we position marginal crease in the ginguival sucus that should rush the
      accumulation of the plaque. The bacteries in the plaque would cause the
      inflammation of ginguive. The end of the crown edge in gingival sucus would cause
      chronic inflammation at ginguival tissue. The existence of transit zone that
      includes the crown edge, prepared tooth and dental cement became important if the
      crown edge has been positioned subgingivaly. If the crown edge ends in the
      ginguival sucus, the tooth meat is constantly being irritated that results with
      different degrees of inflammations. In many cases it causes ginguival
      dislocation. The possibility of clinical control of marginal positioning of
      subgingivaly positioned crown edge on demarcation line does not exist in terminal
      phase of cementing. The crown cement can be substratum of bacterial receptiveness
      and the plaque accumulation in the ginguival sucus. The procedure of cementing is
      an important cause of incomplete edge closing of the crown on the demarcation
      line. The form of demarcation line determine the form and the width of crown.
      They are favorising and degrading the level of marginal adaptations. The existing
      of horizontal discrepancy at the relation of based tooth--the crown edge is
      unavoidable. The question is if the amount of this discrepancy fits the assumed
      biological optimum.

PMID- 9601796
TI  - [Telepathology and present experience based on use of the SHARED
      telecommunication project].
AB  - Telemedicine is rather new activity covering various approaches in order to
      fulfill the main task which can be expressed in more comprehensive words such as
      "remote medicine" or "medicine on distance". One of definitions of telemedicine
      given by the European Commission for Telemedicine says that "telemedicine is fast
      access to distributed medical expert knowledge using telemedicine and information
      technologies regardless of actual location of a patient or relevant information".
      The first connection has been established with Zagreb, Croatia in September by
      means of PHAROS. In October 1996 the Institute of Pathology with the Radiology
      and Ophthalmology Clinics of University hospital of Sarajevo has joined the
      experimental project "SHARED" (a telemedicine initiative to support remote health
      care structure, proposed by the San Raffaele International Biomedical Science
      Park with Stato Maggiore della diffesa and European Space Agency). Due to
      problems in infrastructure and lack of experts, small country like Bosnia and
      Herzegovina (BiH) sees telemedicine as future in its health care organizing.

PMID- 9601797
TI  - [Electronic medical records in Bosnia-Herzegovina. The electronic card--the
      medical record of the future in Boznia-Herzegovina].
AB  - The biggest problem in organisation of the effective and rational health care of
      good quality in Bosnia quality and Herzegovina is a functional and updated Health
      Information System. In this system, important role play Health Statistic System
      in which documentation and evidence are very important segment. Developed
      countries proceeded from the manual and semiautomatic method of medical data
      processing and system management to the new methods of entering, storage,
      transfer, searching and protection of data using electronic equipment. Recently,
      the competition between manufacturers of the Smart Card and Laser Card is
      reality. Also scientific and professional debate exists about the standard card
      for storage of medical information in Health Care System. First option is
      supported by West European countries that developing Smart Card called Eurocard
      and second by USA and Far East countries. Because the Health Care System and
      other segments of Society of Bosnia and Herzegovina innovate intensively similar
      systems, the authors of this article intend to open discussion, and to show
      advantages and failures of each technological medium.

PMID- 9601798
TI  - [Radiovisiography--a modern method of diagnosis in stomatology].
AB  - Radiovisiography is a modern diagnostic method based on use of digital rentgen.
      Principle is use of so called CCD chip in sensor that is put in patient's mouth.
      Information are stored and, after processing, are reproduced as rentgen picture
      on screen or photo on printer. Appropriate software that support rentgen picture
      processing in several dimensions is used. Advantages comparing to classical
      rentgen are great. Principle machine works, hardware and software performances,
      advantages and disadvantages comparing to classical method are described in the
      paper.

PMID- 9601800
TI  - [Dr. Mehmed Sami Serbic (1847-1918)--founder of organized health care in the
      Tuzla region].

PMID- 9601799
TI  - Evaluation of data in cardiology by new software tools.
AB  - We describe an analysis of cardiology data using new software tools. First we use
      data of 1417 men aged 40 to 50 years living in the center of Prague gathered in
      the twenty years lasting longitudinal study. We show some results of application
      of the programs E.T. (Epidemiology Tools) and CORE (COnstitution and REduction of
      data). Second we show the way of application of the program HYPERTENSION, that
      supports decision making in therapy of arterial hypertension.

PMID- 9601801
TI  - Detection of metals in tissues, cells and subcellular organelles.
AB  - The current state of art in the detection of metals in tissues, cells and their
      subcellular fractions has been reviewed. Both classic chemical techniques
      (including titration, spectrophotometric, electrochemical and isotope methods,
      neutron activation analysis, mass spectrometry, inductively coupled plasma) and
      cell biology techniques (i.e. conventional histochemical methods,
      autometallography, autoradiography and microanalytical techniques using beam of
      electrons or protons, laser, X-ray or ion beam) were discussed. This survey of
      analytical techniques is, wherever possible, illustrated by examples documenting
      how our knowledge on metals in pigment cells and their subcellular fractions has
      been growing.

PMID- 9601802
TI  - The invasive prenatal diagnosis in perinatal centre.
AB  - Three main methods of prenatal diagnosis (Amniocentesis AMC, Chorionic villi
      sampling CVS and Cordocentesis FBS) have been used in Perinatal Centre of Central
      Bohemia. The chromosomal abnormalities in a group of 3,098 patients have been
      detected in 1.4% of fetuses. The inherited disorders were diagnosed using DNA
      analysis and biochemical examination of amniotic fluid. X-linked diseases in a
      group of 68 patients in 30.8% of fetuses have been diagnosed and inborn error of
      metabolism in a group of 29 indicated patients in 17.2% of fetuses were
      diagnosed. The incidence of fetal losses before 28th week of gestation was 0.4%.

PMID- 9601803
TI  - Assessment of metals and metalloids in skin derivatives of volunteers from
      capital city of Prague, Czech Republic.
AB  - Instrumental neutron activation was employed to determine 12 elements (Al, As,
      Co, Cr, Cu, Fe, Hg, Mn, Mo, Sb, V, Zn) in derivatives of the epidermis (human
      scalp hair, public hairs and toenails) from 188 women and 74 men of the
      population of the Capital City of Prague. Statistically significant differences
      are discussed, occurring during the comparison of groups arranged in terms of
      various factors (type of material analyzed, age, sex, environmental exposure of
      the dwelling and/or occupation locality, type of occupation--mental or manual,
      smoking, alcohol consumption, allergy, hysterectomy and selected diseases).
      Statistically significantly increased levels of elements in materials coming from
      Prague areas with higher environmental burden are considered as the most valuable
      result.

PMID- 9601804
TI  - West syndrome model: seek and you will find.
AB  - West syndrome is an age-specific epileptic syndrome with onset in infancy. It
      comprises infantile spasms (usually flexion convulsions), EEG pattern of
      hypsarrhythmia and mental retardation. Current therapy involves ACTH,
      corticosteroids, valproic acid, pyridoxine and vigabatrine. The treatment is
      difficult and more effective antiepileptic drugs are required. Unfortunately,
      there is no animal model of West syndrome that would accurately depict the
      situation found in humans. N-methyl-D-asparate (NMDA)-induced seizures in infant
      rats have certain features of the West syndrome model. These seizures are age
      specific (they occur before 25 days of age), include hyperflection
      (emprosthotonus), their EEG is not specific and they somewhat respond to
      treatment with the benzodiazepine clonazepam. In 12 and 18 day old rats, we
      tested the effects of hydrocortisone, pyridoxine and sodium valproate against the
      seizures induced by 15 and 45 mg/kg of NMDA i.p., respectively. There were weak
      effects of sodium valproate against the NMDA-induced emprosthotonus. In contrast,
      high doses of pyridoxine were proconvulsant and hydrocortisone worsened the
      damage of nerve cells induced by NMDA. The data show that NMDA-induced seizures
      although similar to West syndrome are extremely resistant to therapy and may not
      be a good model of the West syndrome. However, the search for an adequate model
      that would allow for determination of possible mechanisms and testing of putative
      antiepileptic drugs will continue.

PMID- 9601805
TI  - [Effect of treatment with recombinant erythropoietin in patients with multiple
      myeloma and kidney failure].
AB  - The efficacy of recombinant human erythropoietin (r-HuEPO) in patients with
      multiple myeloma (MM) has been confirmed in several clinical trials. We report
      our experience of r-HuEPO treatment in 5 myeloma patients with renal failure. The
      therapy with r-HuEPO (Eprex, Janssen-Cilag or Recormon, Boehringer, Mannheim) was
      started after 4-8 months from diagnosis, the drug was administered intravenously
      (in one patient subcutaneously after cessation of hemodialysis treatment), two or
      three times weekly. The initial doses were 4-12,000 units/week (mean 8,400). In
      all patients good response during the first month of therapy was observed. Median
      Hb and hematocrit increased from 70 g/l and 20.8% to 87 g/l and 26% after 1 month
      and to 105 g/l and 30.3% after 4-6 months, respectively. The need for blood
      transfusion decreased significantly--from 2.72 TU/month to 0.13 TU/month. WHO
      performance status and patients self-assessment of quality of live improved
      substantially after r-HuEPO. No serious adverse events, including hypertension
      and/or thromboembolic events were observed. In accordance with some previous
      reports we conclude r-HuEPO is effective and safe treatment in patients with MM
      and renal failure. Moreover, lower doses of growth factor could be effective in
      this particular group of patients.

PMID- 9601806
TI  - [DHEA: another hormonal modulator of bone blood flow in rats].
AB  - Dehydroepiandrosterone (DHEA) is a steroid with important effects on the bone
      tissue. We tried to check up if it influenced also the bone blood flow (similarly
      as estradiol and testosterone). We administered DHEA (Sigma) dissolved in
      dimethylsulphoxide s.c. three times weekly for four weeks in the doses of 15-20
      mg per rat on 125 mg/kg body weight to female rats--sham-operated or
      oophorectomized (OOX). In two experiments (A and B) we ascertained the uptake of
      85Sr-microspheres, local blood flow, cardiac output, density and ash weight of
      the burned tibia, in the third experiment (C) 24 hour incorporation of 45Ca and
      3H-proline into the bone. The 85Sr-microsphere uptake in the tibia was elevated
      after OOX in both experiments A and B; this increase was inhibited completely
      (and statistically significantly versus the OOX group) by the administration of
      DHEA. Similar and also significant reactions were found in the microsphere uptake
      values in the distal end of femur. No significant changes could be demonstrated
      in the diaphysis of femur and calvaria as well as in the cardiac output, output,
      blood pressure and heart rate. The incorporation of 45Ca and 3H-proline into the
      tibia (experiment C) was significantly increased after OOX. The administration of
      DHEA inhibited this increase significantly in the values of 3H-proline. The
      density of tibia in both experiments A and B and ash weight of tibia in
      experiment A, suppressed after OOX, were significantly increased after the
      administration of DHEA to OOX females. The results show that also DHEA--in the
      experimental conditions used--has similar effect on the bone blood flow as
      estradiol and testosterone.

PMID- 9601807
TI  - [Use of multivariate analysis in medical chemistry].
AB  - Alternations in trace elements concentrations are intensively studied because of
      their possible role in pathogenesis and progress of diseases. Three groups of
      patients were investigated: haemodialysis patients (HD) (n = 17), continual
      ambulatory peritoneal dialysis patients (CAPD) (n = 11), and control group of
      blood donors (n = 12). They were analyzed for Se, Zn and Cu concentration in
      plasma and erythrocytes by inductively--coupled plasma mass spectroscopy.
      Distribution of analyzed elements between these blood compartments was found
      different in all groups of studied patients. Erythrocytes were enriched by Se
      (twofold higher concentration compared to plasma) and by Zn (10-20 fold higher
      concentrations compared to plasma). On the other hand, human plasma was enriched
      by Cu (approximately twofold higher concentration then in erythrocytes). Results
      of analyses were processed by multivariate analysis of variance (MANOVA). When
      only results of plasma analysis were involved into MANOVA, differences between HD
      patients and other two groups were found whereas CAPD and control group were not
      distinguished each other. However, these two groups were mutually differenced
      when MANOVA comprised all trace elements concentrations: both plasma and
      erythrocytes. Methods of multivariate statistic are able to study not only the
      individual variables but even their mutual relations and their medical
      applications are very useful.

PMID- 9601808
TI  - [Experimental animals--present status and future perspectives].

PMID- 9601809
TI  - [Review--evaluation--peer review. Suggestions for beginning reviewers].

PMID- 9601810
TI  - The enzymatic characters of papain from melony tree fruits growing in Uzbekistan.

PMID- 9601811
TI  - Embryonic development of spontaneous motility in chick embryos. Identification of
      participation of NMDA-mechanism by magnesium ions.
AB  - The influence of magnesium ions on the spontaneous motility and its development
      was studied in chick embryos aged from day 4 to day 19 of incubation. 1-An acute
      application of MgCl2 (80 mg/kg e.w.) evoked from day 13 of incubation a
      significant depression of spontaneous motility together with decreased
      synchronization of embryonic spontaneous movements. 2-The resting spontaneous
      motility in 17-day-old embryos after chronic continual application of MgCl2 (11.5
      +/- 1.21 mg/kg e.w./24 h.) from day 4 to day 12 (Mg2+/ser.C) was reduced and
      exhibited smaller synchronization of spontaneous movements by the preponderance
      of movements with moderate amplitude. 3-The chronic application of MgCl2
      expressed itself also by the changed reactivity of spontaneous motility to the
      factors influencing NMDA- and NO-ergic mechanisms. The decrease of NMDA
      activatory effect, the weakened depressory effect of ketamine, the reduction of
      periodic depressive effect of arcaine and the reduction of activatory effect of
      cocktail (NMDA + L-arginine) took place. 4-The investigated effects of Mg2+
      confirm the participation of NMDA-ergic mechanism and simultaneously point out
      the possible role of NO-ergic mechanism in the genesis and the development of
      spontaneous motility in chick embryos.

PMID- 9601812
TI  - Methods for determination of vitamins A and E our simple HPLC assay.
AB  - Biological effects of reactive oxygen species and other radicals which are
      controlled by antioxidant mechanism are exerted on the basis of enzymes and
      substrates. Antioxidant substrates are divided into lipophilic and hydrophilic
      groups. Main representants of lipophilic antioxidants are retinol and tocopherol
      which are closely related to ascorbate in the hydrophilic compartment. Described
      methods for detection of retinol and alpha-tocopherol are simple, sensitive,
      specific and precise. They are reliable, economic and fast. Only small amounts of
      serum are used for one analysis which is convenient for patients, too. Our
      methods can be recommended for routine use in laboratories of clinical
      biochemistry. Haemodialyzed patients, retinol serum level was higher than that in
      blood donors while alpha-tocopherol serum level did not differ. Both vitamin A
      and E serum levels were similar in alcoholics compared to controls.

PMID- 9601813
TI  - Chymocell--a new wound cleansing agent.
AB  - A new wound cleansing agent consisting of bead cellulose with covalently, firmly
      bound proteolytic enzyme, chymotrypsin, was prepared. It was found that this
      preparation can be applied in the treatment of suppurating wounds of all types
      with very good results.

PMID- 9601814
TI  - [Effect of fish oils on plasma lipid risk factors and esterified fatty acids in
      primary hyperlipoproteinemia].
AB  - BACKGROUND: Some epidemiological, clinical and experimental studies have shown
      that intake of n-3 fatty acids (FA) lowers the incidence of coronary heart
      disease (CHD). The effects of fish oil and n-3 FA on the development of
      atherosclerosis include several factors such as the platelet-vascular wall
      interaction, modulation of eicosanoid metabolism as well as platelet aggregation
      and its survival time. There were also changes in the fibrinolytic system and
      cardiovascular reactivity observed. Effects of n-3 FA on lipid and lipoprotein
      metabolism exert antiatheromatous action as well. The aim of the study was to
      evaluate changes in plasma lipid risk factors for CHD in subjects with primary
      hyperlipoproteinemia (HLP) after the administration of fish oil rich in n-3 FA.
      METHODS AND RESULTS: A total of 82 patients (61 men and 21 women) were
      administered fish oil (3.5 g n-3 FA daily) for a period of 3 weeks. The group of
      hyperlipidemics included 9 patients with HLP IIA, 29 with HLP IIB, and 35 with
      HLP IV. Seven patients had HLP type V while two had HLP type III. Intake of fish
      oil led to a mild decrease in total plasma cholesterol which was significant in
      the whole group and in HLP type V. Triglyceride levels declined significantly in
      all HLP phenotypes, with the changes being most marked in HLP types IIB, IV, and
      V. We also observed a significant increase in cholesterol concentration in HDL
      and in the both HDL2 and HDL3 subfractions in the whole group and all HLP
      phenotypes as well. On the other hand no statistical significant changes were
      observed in LDL-cholesterol levels. The levels of apo B rose significantly only
      in HLP type V. A statistically significant increase was found in apo A-1 levels
      in the whole group and in the HLP IIB subgroup. Fish oil administration led to a
      mild reduction in diastolic pressure and uricemia. In part of patients fish oil
      induced decrease in lipoprotein(a) concentration was observed.

PMID- 9601815
TI  - Business ethics as a novel issue in health care economics.
AB  - The problems of health care providing and solutions suggested to solve them
      should be discussed publicly at all appropriate levels in all developed
      countries. In this contribution, new approaches to understanding the problems of
      business ethics in health care are mentioned and recommended for discussion. An
      application of such principles of business ethics as trust, accountability,
      solidarity, transparency and social responsibility is considered in the four
      following areas. First, it is the allocation of limited resources in health care.
      This is the world-wide problem of the end of 20th century, as the development of
      medical technologies offers a wide range of new diagnostic and therapeutic
      procedures. In our country this coincides with the on-going, and still
      incompleted reform of health care. Second, the other area is that of connecting
      health-care and social problems, important namely for vulnerable groups such as
      children, the elderly and chronically ill. The third area is concerned with the
      privatization of health care, the newly emanating structure and function of the
      health care system and the role of health care provides in society. The last
      group contains issues concerning attempts to facilitate communication between
      health care specialists and general public, as well as attempts to support those
      institutions of the civic democratic society that are oriented toward health,
      sickness and health care providing.

PMID- 9601816
TI  - Are there limitations of VATS surgery?

PMID- 9601817
TI  - The Ethics Committee of the General Faculty Hospital and First Medical Faculty,
      Charles University.
AB  - The purpose of this contribution is to inform about the activities of the local
      ethics commission established at one of our largest teaching (University)
      hospitals. In 1995 the following priorities were recognized: studying
      international ethical standards of research involving human subjects and strictly
      adhering to them; bilingual administrative agenda in Czech and English; enforcing
      the patients' rights in health care and emphasizing them in education of medics
      and other students of health related disciplines; stimulating effective
      communication between doctors, other health care workers and lay persons in the
      commission as well as between the members of the commission and authors of
      research projects applying for ethical evaluation. Since 1993 the commission has
      been revising and storing in the archives more than 600 research projects. In
      1996, 181 new research projects were reviewed, which is 35% more than in 1995.
      Approval was granted in 154 cases (85.08%), 3 cases (1.66%) were rejected, 15
      cases (8.29%) approved on condition of complying with the recommendations of the
      commission, 6 cases (3.31%) recommended for another commission, and in 3 cases
      reviewing the project was postponed for lack of necessary data. The members of
      the commission agree that the future activities should lead to forming a broader
      group of consultants of the commission and other professional and lay people
      interested in clinical ethics. According to their meaning, legislation concerning
      ethical commissions in the Czech Republic, including material and financial
      support and administrative help, is urgently needed.

PMID- 9601818
TI  - [Science Citation Index and Current Contents. Basic information for users].

PMID- 9601819
TI  - [Impact factors?!].

PMID- 9601820
TI  - [Thoughts on the impact factor].

PMID- 9601821
TI  - [Visits are permitted 24-hours-a-day 365-days-a-year...].

PMID- 9601822
TI  - [Progress and current trends in oral implantology].

PMID- 9601823
TI  - [Methods for the diagnosis and follow-up of caries. When to drill?].

PMID- 9601824
TI  - Post-transplant lymphoproliferative disorders.

PMID- 9601825
TI  - D. J. du Plessis Lecture. Surgical research--reflections and a vision. Delivered
      at the University of Stellenbosch, 17 July 1997.

PMID- 9601826
TI  - Laparoscopic cholecystectomy--an audit from Durban.

PMID- 9601827
TI  - Plasma volume expansion with Haemaccel does not impair haemostasis during
      reduction mammaplasty.
AB  - OBJECTIVES: An in vivo study under well-controlled conditions was undertaken to
      determine the effect of Haemaccel, a colloidal plasma volume expander, on normal
      haemostasis. METHODOLOGY: Twenty patients, who were admitted for reduction
      mammaplasty, were included in this study. A standardised anaesthesia protocol was
      followed with all patients. Ten patients received 500 ml Haemaccel and 10
      controls received 1,500 ml Ringer's lactate, a crystalloid solution. The
      solutions were administered intravenously during surgery over a period of 30-40
      minutes. Standardised clinical observations and haematological tests were done at
      the following time intervals: after anaesthesia but before infusion of the plasma
      substitute, immediately after infusion was completed, and 20, 40 and 60 minutes
      after infusion. RESULTS: The blood pressure, pulse rate and O2 saturation levels
      were not influenced by the treatment given. Haemodilution was similar for the two
      patient groups. The platelet count and plasma levels of fibrinogen decreased in
      parallel with haemodilution. Thereafter the platelet count gradually increased to
      pre-infusion counts at 60 minutes. The prothrombin time (PT), activated partial
      thromboplastin time (aPTT), thrombin time (TT) and platelet aggregation in
      response to adenosine diphosphate (ADP) and collagen were not affected by the
      plasma volume expander given. Arachidonic acid-induced aggregation decreased
      significantly after Ringer's lactate was given but did not change when Haemaccel
      was given. The bleeding time was prolonged slightly, but not significantly, from
      7.4 +/- 1.6 minutes to 8.8 +/- 1.6 minutes with Ringer's lactate and from 6.9 +/-
      2.0 to 9.7 +/- 3.7 minutes with Haemaccel. CONCLUSIONS: We could not find any
      scientific evidence that Haemaccel affects haemostasis; neither does it increase
      bleeding relative to Ringer's lactate.

PMID- 9601828
TI  - Sequelae of cholecystojejunostomy for benign intrapancreatic biliary strictures.
AB  - The case histories of 5 patients who presented with recurrent jaundice following
      cholecystojejunostomy for biliary decompression of benign intrapancreatic
      strictures were studied. Four developed episodes of severe cholangitis 2-9 years
      after their initial operation. A subsequent surgical intervention was undertaken
      in 3 patients, 2 of whom died from cholangitis. The fourth patient experienced 3
      episodes of cholangitis, declined surgical intervention and died. The fifth
      patient presented 4 months after the first procedure with a transient
      cholangitis. Cholelithiasis and cholangitis may take several years to develop but
      seem inevitable when cholecystojejunostomy is used to decompress benign biliary
      obstruction. Its use in suspected benign biliary obstruction should be abandoned.

PMID- 9601829
TI  - Diffuse leiomyomatosis of the oesophagus--a case report.
AB  - A case of diffuse leiomyomatosis of the oesophagus is described. The patient
      presented with progressive dysphagia and severe loss of weight. Barium swallow
      revealed a massively dilated oesophagus. The patient was treated by oesophageal
      resection, but died 12 hours after the operation.

PMID- 9601830
TI  - Synovial sarcoma of the parotid gland. A case report with clinicopathological
      analysis and review of the literature.
AB  - Primary sarcomas of the major salivary glands are exceptionally uncommon.
      Synovial sarcoma is a distinctive neoplasm which usually arises in the
      extremities in the region of joints. Although synovial sarcomas arising in the
      head and neck region are well described, tumours actually originating in and
      around the major salivary glands are exceedingly rare, with few cases reported in
      the literature. We report a synovial sarcoma in the right parotid gland of a 67
      year-old man. The literature pertaining to salivary gland sarcomas and synovial
      sarcoma of the head and neck region is reviewed.

PMID- 9601831
TI  - Transcutaneous electrical nerve stimulation in the treatment of myofascial pain
      dysfunction.
AB  - The effect of transcutaneous electrical nerve stimulation (TENS) plus
      conservative therapy (ibuprofen, bite plate, self-physiotherapy) on myofascial
      pain dysfunction (MPD) was determined. A single-blind trial as done in 10
      patients with MPD with subthreshold TENS (frequency 35 Hz, pulse width 100
      milliseconds, modulation 50%) compared with sham TENS at 8 visits over 14 weeks.
      Pain was assessed on a visual analogue scale before and after TENS at each visit
      and the data were analysed with the analysis of variance (ANOVA) for repeated
      measures. A highly significant effect was seen for time (F = 4.80, P = 0.0003)
      but not for TENS. Subthreshold TENS did not increase the symptom relief produced
      by conservative treatment with the protocol used.

PMID- 9601833
TI  - [Relation between serum amino acids and insulin sensitivity (results of a clamp
      study in offspring of hypertensive patients].
AB  - Hypertension which is part of the metabolic syndrome has frequently a family
      background. The authors investigated therefore indicators of insulin sensitivity
      by the method of a hyperinsulinaemic euglycaemic clamp in the offspring of
      hypertensive probands. In conjunction with the increased interest in the role of
      muscles in influencing insulin sensitivity the authors were also interested in
      serum amino acid levels. They examined a group of 15 healthy offspring of
      hypertonic subjects (PHT) and compared them with a group of 18 healthy volunteers
      without a family-history of hypertension. PHT had as compared with controls a
      higher systolic pressure (117 +/- 7.2 mm Hg vs. 106.1 +/- 11.7 mm Hg p < 0.01).
      In the clamp examination in PHT significantly lower indexes of tissue insulin
      sensitivity were recorded, SI (46.51 +/- 11.8% vs. 54.3 +/- 7.79%, p = 0.02) and
      ISI (6.6 +/- 3.99 vs. 9.88 +/- 5.05, p < 0.01). In the PHT group were, in
      addition to the different ratio of some branched chain amino acids and tyrosine,
      also relations between indicators of insulin sensitivity and arginine. It is thus
      obvious that signs of reduced insulin sensitivity are present in PHT already in
      the preclinical stage. Relations between the altered insulin sensitivity and
      arginine, the precursor of nitrogen oxide, apparent only in PHT could be a
      stimulus for seeking associations with endothelial damage described in insulin
      resistant conditions.

PMID- 9601832
TI  - [Use of drug therapy in hyperlipidemia in patients after myocardial infarct in
      the Czech Republic].
AB  - The use of hypolipidemic drugs has been analyzed in 1,113 patients after
      myocardial infarction using a questionnaire with data entered from the medical
      records by spa physicians. 80.1% of patients had total cholesterol values > 5.2
      mmol/l; mean value being 6.16 +/- 1.08 mmol/l. Mean values of LDL-cholesterol
      were 4.05 +/- 0.1 mmol/l, of triglycerides 2.01 +/- 1.14 and of HDL-cholesterol
      1.26 +/- 0.61 mmol/l. Hypolipidemic drugs were used only in 16.5% patients with
      total cholesterol values above 7.0 mmol/l, in 14.4% patients with total
      cholesterol values 6.2-7.0 mmol/l and in 11.4% of patients with cholesterol
      values 5.2-6.2 mmol/l. Even some patients with cholesterol more than 8.0 mmol/l
      were not treated by hypolipidemic drugs. The most frequently used drugs were
      fibrates (phenofibrate, gemfibrozil)--in 89.5% patients. Statins were used only
      in 7.5% patients receiving hypolipidemic drugs. Our results show that in contrast
      to the US and European Recommendations for hypolipidemic drug therapy in patients
      with CHD, this treatment is still infrequently used by Czech cardiologists and
      internists. This discrepancy is even more apparent when comparing it with other
      life prognosis improving drug therapies in this group of patients. Antiplatelet
      drugs, mainly ASA were used in 85.5% patients, beta-blocking drugs in 59.3%
      patients and ACE inhibitors in 55.9% patients with left ventricular systolic
      dysfunction. Thus hypolipidemic therapy in CHD is the key problem of drug therapy
      in patients after myocardial infarction in the Czech Republic.

PMID- 9601834
TI  - [Nutritional status in patients with chronic obstructive pulmonary disease].
AB  - The authors examined the nutritional status of 50 patients admitted on account of
      exacerbation of chronic obstructive lung disease. The mean height of patients was
      168 +/- 8.8 cm, the body weight 72.2 +/- 16.2 kg, BMI 25.5 +/- 5.5 kg/m2. The
      mean albumin concentration was 33.1 +/- 4.6 g/l, transferrin 2.3 +/- 0.6 g/l, the
      skinfold thickness 17.3 +/- 9.9 mm, arm circumference 28.6 +/- 7.2 cm. The mean
      energy expenditure at rest (REE) was 122.1 +/- 12.3%. The total number of
      undernourished patients was 7 (14%), there were 27 obese patients (54%). The
      authors did not find a relationship between respiratory parameters and values of
      blood gases on the one hand and body weight, skinfold thickness, BMI, REE, arm
      circumference, albumin, transferrin and the number of lymphocytes on the other
      hand. This is obviously due to the fact that the group comprised more obese than
      undernourished patients. Obese and undernourished patients were found in all
      three stages of the disease.

PMID- 9601835
TI  - [Percutaneous endoscopic gastrostomy in nutritional therapy--personal
      experience].
AB  - The authors have described the indications, contraindications of percutaneous
      endoscopic gastrostomy (PEG) and its consecutive nutritional possibilities. They
      have described their own experience with 11 patients. Most common indications for
      the placement of a gastrostomy tube were neurological, and only in one case,
      esophageal diverticle. The average duration of PEG was 102 days (2-732). Besides
      PEG, not only polymeric diet, such as Nutrison standard sol, Fresubin,
      Salvimulsin, was administered, but also home-made diet, for example, mixed soup,
      mashed potatoes, yoghurt, juice and cocoa. The diet prepared at home was
      tolerated well, except for subjective data about meteorism given by one female
      patient. PEG complications were minimal, in one case a dry fistula was detected
      after the extraction of PEG; it was closed spontaneously a week later. Another
      female-patient showed leukocytosis and hyperpyrexia, the etiology of which could
      not be proved. The patient was treated symptomatically, and three days later,
      leukocytosis and hyperpyrexia were normalized. A patient who has had the
      gastrostomy tube placed for two years, showed secretion which was treated
      symptomatically; now the patient is without any complications. In the last
      patient, there was detected an inflammation around the fixation base. Although
      she was treated with H2 blockers, the condition has not been improved. The
      authors have recommended this method in correct indications as a considerate
      alternative application of enteral nutrition.

PMID- 9601836
TI  - [Famotidine in the treatment of gastropathy induced by non-steroidal
      antirheumatic agents].
AB  - In an open clinical endoscopically controlled study in 30 consecutive patients
      with rheumatic diseases complicated by the ulcerative and erosive form of
      gastroduodenopathy induced by non-steroidal antiinflammatory drugs and
      oesophagitis, after four weeks treatment with oral famotidine (one dose of 40
      mg/day) confirmed a significant improvement of the mean oesophageal (0.67 +/-
      1.06 vs. 0.03 +/- 0.18, p rrr 0.01) gastric 2.10 +/- 1.49 vs. 0.63 +/- 0.85, p
      rrr 0.001) and duodenal mucosal score (1.80 +/- 1.52 vs. 0.43 +/- 0.82, p rrr
      0.001). After four weeks treatment 71% lesions (5/7) in the oesophagus were
      cured, 77% gastric lesions (10/13) and 75% duodenal lesions (9/12). Treatment
      with non-steroid antirheumatics proceeded.

PMID- 9601837
TI  - [Esophageal echocardiography in patients with cerebrovascular stroke and atrial
      fibrillation].
AB  - Atrial fibrillation is an important risk factor of embolization into the CNS.
      Thus affected patients should receive permanent anticoagulant therapy.
      Oesophageal echocardiography (TEE) can help our decision in patients with
      relative contraindications of anticoagulant therapy. TEE was performed in 52
      patients with atrial fibrillation and cerebrovascular attack (CMP) with an
      ischaemic aetiology. Transthoracic echocardiography did not reveal the source of
      embolization. In 10% patients a thrombus was found in the appendage of the left
      atrium, in another 9% patients a spontaneous echocontrast was found in the left
      atrium (prethrombotic condition) and in 5% patients an open foramen ovale. The
      results indicate the highly probable etiology of embolization in patients with
      cerebrovascular attacks and atrial fibrillation. This supports the recommendation
      of absolute indication of anticoagulant treatment in patients with
      cerebrovascular attacks and atrial fibrillation.

PMID- 9601838
TI  - [Bone changes in ulcerative colitis].
AB  - One of the complications of ulcerative colitis with frequent relapses is mineral
      deficiency (potassium, calcium, magnesium and phosphorus). The objective of the
      present work is to examine the bone density and laboratory parameters of bone
      metabolism in 25 patients with a medium severe and severe form of ulcerative
      colitis. In patients with ulcerative colitis a significantly reduced bone density
      was found in the era of neck of the femur (p < 0.05), a a non-significantly
      reduction of the bone density in the era of the lumbar vertebrae and an elevated
      level of osteocalcin (p < 0.05). These findings indicate a higher prevalence of
      bone changes in patients with ulcerative colitis. Early detection of bone changes
      makes adequate prevention and treatment of bone complications possible.

PMID- 9601839
TI  - [Is quinidine an outmoded drug?].
AB  - In a group of 273 patients with a recently developed atrial fibrillation the
      authors compared the success of cardioversion in a group of 141 patients using
      quinidine and a group of 132 patients where for cardioversion different
      preparations were used. The results of the investigation confirmed the advantages
      of quinidine as an antiarrhythmic drug used for pharmacological cardioversion of
      atrial fibrillation.

PMID- 9601840
TI  - [Clinical aspects of use of beta-blockers in the treatment of arterial
      hypertension].
AB  - The author presents a brief account on the mechanisms of action of beta-blockers
      in arterial hypertension. He mentions mainly clinical aspects of treatment with
      beta-blockers. A basic classification is presented with an account on different
      substances. Indications of beta-blockers are discussed as well as their
      combinations with other hypotensive drugs not only in the treatment of arterial
      hypertension but also in concomitant diseases such as ischaemic heart disease and
      other pathological conditions. In the conclusion the author mentions the most
      frequent side-effects of beta-blockers and their contraindications.

PMID- 9601841
TI  - [Principles of monitoring patients with exacerbation of chronic obstructive
      pulmonary disease].
AB  - In patient treated on account of exacerbations of chronic obstructive pulmonary
      disease the authors monitor the peak expiration frequency (PEF) or spirometry,
      blood gases, pulse and respiration rate, grade of dyspnoea, ECG, blood count,
      blood sugar level, serum lactate concentration theophyllinaemia. It is necessary
      also to make an X-ray examination of the chest and bacteriological examination of
      sputum. The authors describe the method of different examinations and the
      relationship of the monitored parameters to the pathophysiology of the disease.

PMID- 9601842
TI  - [Mushroom poisoning--classification, symptoms and therapy].
AB  - The most serious poisonings are the hepatotoxic ones which are caused above all
      by Amanita phalloides, virosa, verna, Lepiota helveola, Galerina marginata,
      Gyromitra esculenta, Hypholoma fasciculare, and nephroptoxic intoxications which
      are caused above all by Cortinarius orrelanus and Paxillus involutus. Neurotoxic
      and psychotropic intoxications develop after ingestion of Inocybe, Clitocybe,
      Amanita-panterina, muscaria and Psilocybe. Most frequently the gastroenteric type
      of mushroom poisoning is encountered which is caused by many species e.g. Boletus
      satanas, Entoloma sinuatum and others. In the diagnosis anamnestic data are used,
      the clinical picture, mycological and toxicological examinations of residues of
      mushrooms, their spores and toxins. Therapeutic strategy comprises elimination
      methods gastric lavage, intestinal lavage and administration of large amounts of
      animal charcoal, forced diuresis, haemoperfusion, haemodialysis or peritoneal
      dialysis, administration of antidotes and symptomatic treatment, i.e. mainly
      rehydration and restoration of the mineral balance. Early and comprehensive
      treatment are important.

PMID- 9601843
TI  - [Bisphosphonates, their mechanism of action and properties useful in the therapy
      of metabolic bone diseases].
AB  - Bisphosphonates are a group of chemical substances which have been used in
      medicine for thirty years in the treatment of skeletal diseases and disorders of
      calcium metabolism. Bisphosphonates are derived from pyrophosphate by
      substitution of an O atom for a C atom. This structure makes possible a number of
      variants by changing the side-chains of the C atom. The basic P-C-P bond is very
      thermostabile and completely resistant to enzymatic hydrolysis. The basic
      biological property of bisphosphonates is inhibition of bone resorption but has
      not been completely elucidated so far. The prerequisite is the inhibitory action
      of bisphosphonates on osteoclast activity. The latter are inhibited only when
      they are in contact with bone surfaces which contain bisphosphonates. Another
      possible mechanism of action of bisphosphonates is their action on osteoblasts:
      osteoblasts produce local growth factors which inhibit osteoclasts and thus
      osteoresorption is inhibited. So far it is not exactly known whether the direct
      effect on osteoclasts, the indirect effect via osteoblasts or a combination of
      both are the most important effect of bisphosphonates on the resorption of bone.

PMID- 9601845
TI  - [Combined disorders of the acid-base equilibrium. Clinical comments].
AB  - The submitted paper contains comments on the evaluation of combined disorders of
      the acid-base balance. Some different definitions of the acid-base balance are
      given as well as their importance for the evaluation of combined conditions. The
      author discusses parallel and opposite deviations which develop inside and
      outside the cell, disorders associated with the mere accumulation of some ions
      and disorders associated with an impaired energy balance. On several examples
      clinical manifestations of impaired acid-base balance are illustrated where the
      laboratory finding may be atypical.

PMID- 9601844
TI  - [Pancreatic diabetes].
AB  - A review of recent data from the literature on the pathophysiology and clinical
      aspects of pancreatogenic diabetes, carcinoma of the pancreas and conditions
      after pancreatectomy. It deals with the secretion of insular hormones, insulin
      sensitivity and contraregulatory mechanisms. On these findings, not always
      complete, adequate treatment should be based.

PMID- 9601846
TI  - [Current views on use of megestrol acetate in oncology practice].
AB  - Anorexia of tumourous origin associated with cachexia is a frequent clinical
      problem which has a substantial impact on the therapeutic results and patient
      survival. It is encountered in as many as 90% patients in the stage of palliative
      care. Tumourous cachexia is thus a difficult problem in oncological practice.
      Hormonal therapy of malignant breast disease is an integral part of adjuvant as
      well as palliative treatment in postmenopausal as well as premenopausal patients.
      Both oncological problems, tumourous cachexia and hormonal therapy interfere by
      their consequences with the quality of life of oncological patients, i.e. a
      situation which is becoming the pillar of care of oncological patients. The
      author reviewed the contemporary available literature pertaining to tumourous
      cachexia and hormonal therapy of breast cancer. He emphasizes the mechanism which
      participates in tumourous cachexia and discusses possibilities to influence it by
      therapy. Megestrol acetate (Megace, Bristol-Myers Squibb Co.) proves so far the
      most effective pharmacological preparation which improves anorexia and cachexia
      in severely ill patients. In the review of the literature the author presents
      examples of the use of megestrol acetate in the hormonal strategy of treatment of
      breast cancer and mentions some problems which deserve further study. The
      objective of the submitted review is to draw attention of the medical community
      to a drug which is a stimulant in the comprehensive, pretentions strategy of
      treatment of malignant diseases and which leads by its basic action also to
      improvement of the quality of life of these patients.

PMID- 9601847
TI  - [Hemoglobin Hana or alpha 2 beta 2 63 (E7) His-Asn: a new unstable hemoglobin
      variant with a paradoxically different clinical manifestations in smokers and non
      smokers in the same family].
AB  - The authors describe the identification and the clinical manifestations of a new
      structural variant of haemoglobin found in three subjects from two generations of
      a Moravian family. It is manifested by mild haemolytic anaemia with Heinz bodies
      in the proband and a slightly elevated value of methaemoglobin. The sequential
      analysis of the beta-globin gene provided evidence that the cause is mutation CAT
      AAT in codon 63 which leads to the exchange of distal histidine /E7/ for
      asparagine. The ratio of beta X:beta A is 38:62. The mother with the same
      mutation is asymptomatic. The relative amount of beta X:beta A mRNA transcripts
      in mother and daughter are equal. This indicates that the clinical differences
      are not due to a different gene expression. The mother is a heavy smoker with an
      elevated CO-Hb level that probably protect the mutant against oxidative
      denaturation and increases thus the stability of Hb-Hana. The authors discuss
      also the finding of two abnormal stripes assessed by three electrophoretic
      methods.

PMID- 9601848
TI  - [A fully implantable port system for venous access. Personal experience with 91
      patients].
AB  - A fully implantable venous port system with a cannula inserted into the central
      venous system was implanted to 91 patients. The system was used for the
      administration of different types of intravenous preparations, incl. transfusions
      of erythrocyte mass and parenteral nutrition. With in the framework of autologous
      transplantation via the port system haematopoietic progenitor cells from the
      peripheral blood stream were administered. Part of the introduced systems was
      used for monitoring of the central venous overpressure and for collecting blood
      samples. The system was introduced on an average for 289 days, with a median of
      245 days, range 82-872 days. During the implantation seven complications
      developed, in three instances the port was removed prematurely. During treatment
      16 complications were observed, which in six instances led to early explantation
      of the venous port. The number of complications in total amounted to 0.87 per
      1000 treatment days. The system was well tolerated by the patients because of its
      functional effectiveness and minimal cosmetic changes, and because it is not
      demanding it was also accepted well by the nursing staff.

PMID- 9601849
TI  - [External quality control of hematologic tests in the Czech Republic 1994-1996].
AB  - In 1994 in the Czech Republic external quality evaluation of haemograms was
      started. Quality was evaluated by sending control samples to laboratories and by
      comparing the results of their assessment with the correct value. A permitted
      range to results was assessed: for platelets 24%, for leucocyte 20% and for
      erythrocytes, haemoglobin, haematocrit and the mean corpuscular volume (MCV) 10%.
      The relative error of blood cell count was expressed by means of a coefficient of
      variance. The error declined during the period of evaluation, during the last
      cycle it was 4% for erythrocytes 8% for leucocytes and 10% for platelets.
      Assessment of haemoglobin was of all components of the haemorgram associated with
      the least error, assessment of the haematocrit was less successful. Least
      accurate were laboratories which use manual methods (success rate cca 70%), more
      successful were assessments made by semi-automatic analyzers for blood counts
      (85%), automatic analyzers were successful in 95%. The participating laboratories
      obtained certificates for well assessed parameters.

PMID- 9601850
TI  - [Clinical characteristics of mycosis fungoides and Sezary syndrome].
AB  - Mycosis fungoides and Sezary syndrome are typical representatives of malignant
      lymphomas of the T-series affecting the skin. Both affections have a varied
      clinical picture, a different spectrum of histological and laboratory findings
      and lack a uniform prognosis. In the submitted review the authors discuss in more
      detail all mentioned aspects of the disease and draw attention to new therapeutic
      possibilities.

PMID- 9601851
TI  - [Diagnosis of mycotic infections in oncology patients using the polymerase chain
      reaction].
AB  - Diagnosis of mycotic infections is despite the immense effort devoted to this
      problem still very inaccurate. A new and promising method is the polymerase chain
      reaction, PCR, which theoretically can detect a single cell. In their original
      study the authors decided to develop a new method for the detection of fungi by
      PCR and to compare this examination with post-mortem findings. Thus it was
      possible to determine sufficiently reliably the sensitivity and specificity of
      the method. For the detection of fungi the authors selected the sequence coding
      for a small subunit of ribosomal RNA (18S rDNA). The method is able to detect the
      amount of DNA from some 10-100 cells. The sensitivity was 90% and the specificity
      92%. The method is so far too laborious for common practice, its simplification
      would be however very useful.

PMID- 9601852
TI  - [Clinical findings in individuals with the factor V Leiden mutation].
AB  - Leiden mutation of the coagulation factor V is the most frequent known congenital
      risk factor of thrombophilia. The authors examined a group of 440 subjects with
      thrombosis in the case- or family-history. The mutation was found in 146. In 94
      thrombotic manifestations were recorded in the case-history, five women were
      examined because of repeated abortions. 52.74% carriers of FVL had venous
      thrombosis of the lower extremities and pelvis in their case-history, 19.18% had
      pulmonary embolism in the case-history. In 27.40% during the initial
      manifestations of thrombosis no other risk factor of thrombosis was detected. In
      10.27% the first thrombosis developed after an injury or operation. In 22.22%
      women the thrombosis was manifested during pregnancy or the puerperal period. Due
      to the high incidence of this defect screening of the resistance to activated
      protein C should be an integral part of examination of thrombophil conditions.

PMID- 9601853
TI  - [Treatment of MALT lymphoma of the digestive tract].
AB  - Mucosa-associated lymphoid tissue (MALT) is an autonomous part of the immune
      system with a specific function, histological structure and circulation of cells.
      As a result of malignant transformation of this tissue maltomas develop,
      peripheral extranodal non-Hodgkin lymphomas of B-origin more than two-thirds of
      which are found in the digestive system. The authors investigated in a
      retrospective study the effectiveness of different types of treatment of maltomas
      of the digestive tract with a low and high grade of malignity in 16 patients. It
      appears that splenectomy is not necessary in these patients and that the
      effectiveness of primary chemotherapy with a view of inducing complete remission
      of the disease is comparable with surgical treatment and subsequent adjuvant
      treatment without deterioration of the patient s life by mutilating surgery. An
      integral part of treatment of gastric maltomas is eradication of infection caused
      by Helicobacter pylori.

PMID- 9601854
TI  - [Vascular intercellular adhesive molecule-1 (VCAM-1)--a new indicator of activity
      in systemic lupus erythematosus?].
AB  - The objective of the submitted study was to evaluate the role of the serum level
      of the soluble form of the vascular adhesive molecule-1(VCAM-1) in systemic lupus
      erythematosus (SLE) and to evaluate the possible relation to selected clinical
      and laboratory indicators of activity of the disease and cytokine serum levels.
      The analyzed group comprised 20 women, median age 37 years (range 18-65 years).
      Elevated VACM-1 serum levels were detected in 18 subjects (90%). Statistical
      analysis (Pearson's test, p < 0.05) revealed a significant relationship between
      serum levels of VCAM-1 and the index of clinical activity of SLE evaluated by the
      ECLAM system (European Consensus Lupus Activity Measurement), values of the C3
      complement component, the level of antibodies against dsDNA and serum levels of
      IL-10. No significant correlation was found with levels of the soluble receptor
      IL-2 (sIL-2R) and the C4 complement component in serum. From the investigation
      ensues that investigation of serum levels of the adhesive molecule of the VCAM-1
      type is a promising method which makes early diagnosis of exacerbation of the
      disease possible. However, for evaluation of its real asset in clinical practice
      a more widely conceived longitudinal investigation is needed.

PMID- 9601855
TI  - [IgD plasmacytoma--observations in 5 patients].
AB  - The authors describe five cases of plasmocytoma IgD--two men aged 37 and 49 years
      and three women aged 52, 62 and 80 years. In four instances light lambda chains
      were involved, in one instance kappa chains. In all patients there was a massive
      finding of Bence Jones protein in urine. The diagnosis was assessed after bone
      marrow puncture, immunochemical examination of serum and urine and X-ray of the
      skeleton. In zone electrophoresis of serum a marked gradient was found only in
      three patients. In two instances, where the disease was considered at first
      chronic as glomerulonephritis in the final stage of renal failure, renal biopsy
      helped with the diagnosis. In all patients in the skeleton multiple osteolytic
      foci were found and histological examination revealed a myeloma kidney. In three
      patients affection of organs beyond bone marrow was found and in one patient an
      amyloid. In four patients the progression of the disease was very rapid. The
      patients died within 3-8 months after establishment of the diagnosis. In the
      discussion the authors mention some special features of the clinical course and
      laboratory finding in plasmocytoma IgD.

PMID- 9601856
TI  - [Heparin cofactor II and thrombophilic conditions].
AB  - Heparin co-factor II is in addition to antithrombin III another heparin dependent
      thrombin inhibitor. This glycoprotein blocks thrombin action not only in
      haemostasis but also in its other effects. Congenital deficiency of heparin co
      factor II was found equally frequently among asymptomatic subjects and patients
      with thrombotic complications. Although its deficiency probably is not a serious
      risk factor of thromboembolic disease, it can promote its development in a
      significant way. The authors describe the case of a child with thrombotic
      complications and a congenital deficiency of heparin co-factor II.

PMID- 9601857
TI  - [Therapeutic possibilities in non-Hodgkin's lymphoma].
AB  - The author presents a review of optimal therapeutic procedures in the treatment
      of non-Hodgkin lymphomas (NHL) with a low and high grade malignity. He emphasizes
      that the prerequisite of successful treatment is detailed assessment of the type
      of NHL, the extent of the disease and prognostic signs. Therefore a brief account
      of diagnostic procedures is presented, incl.molecular biological diagnosis.

PMID- 9601858
TI  - [Nucleoli in leukemic cells (overview and personal results)].
AB  - The investigation of nucleoli is a simple but useful complementary approach for
      the evaluation of individual leukemic cells in addition to other hematological
      laboratory procedures. Since main nucleolar types represent the morphological
      expression of nucleolar biosynthetic activities, i.e. RNA transcription, the
      incidence of functionally dominant nucleolar types in leukemic cells reflects the
      state of these cells which is related to that transcription. Similarly, the
      investigation of AgNORs in individual leukemic cells may provide a complementary
      useful information on their proliferation activity.

PMID- 9601859
TI  - [New findings in the diagnosis of minimal residual disease in acute leukemia with
      emphasis on flow cytometry].
AB  - The authors present a review of contemporary findings of investigations of
      minimal residual disease in patients with acute leukaemia. They present brief
      information on different monitoring techniques and on their practical
      application. Attention is paid above all to multiparameter flow cytometry as this
      method is used in their laboratory work.

PMID- 9601860
TI  - [Activation of blood coagulation in oncology patients].
AB  - Thromboembolic complications are a very important part of neoplastic diseases. In
      these complications specific processes participate which are the result of the
      action of substances produced by the tumour or they are formed as a consequences
      of the reaction to the neoplastic disease, its complications or treatment. A
      special role in this respect is played by the tissue factor and cancer
      procoagulant which are very important procoagulant proteins. Post-mortem
      evaluation reveals thromboembolic manifestations in as many as 50% of all
      oncological patients. Considerable attention is paid to the prevention of
      thromboembolic episodes or their progression and patterns for their prevention
      and treatment were elaborated. One of these provisions is the use of anti
      thrombotic drugs, their introduction being motivated by an attempt to check
      coagulation and eliminate its tendency towards hypercoagulation. In this respect
      the importance of heparin is beyond doubt, i.e. of non-fractionated as well as
      low-molecular heparin.

PMID- 9601861
TI  - [The role of the atrium and optimal values of AV intervals in sequentially paced
      patients].
AB  - In 1995, 2249 dual chamber pacemakers were implanted in the Czech Republic. These
      pacemakers make it possible to set an optimal AV delay between the atrial and
      ventricular impulse. Although the optimization of the AV interval has its well
      defined physiologic advantages, it does not seem to be necessary in otherwise
      healthy individuals with a good atrial and ventricular function. In these
      patients the default value, usually about 170 ms, is acceptable. However, AV
      interval optimization--i.e. finding the interval at which the atrial contribution
      to ventricular filling is maximal--should be done in all patients with left
      ventricular dysfunction, indicated for pacing because of bradyarrhthmia. In this
      subset of patients, even a small improvement in ventricular filling is believed
      to be clinically useful. Moreover, it has been documented, that in some types of
      ventricular dysfunction the so-called "primary optimization" (i.e. optimization
      of the AV interval in patients, in whom the pacemaker is not indicated for
      bradyarrhthmia but for ventricular dysfunction that might be improved by AV
      interval optimization) may be clinically useful. It is the case in patients with
      hypertrophic obstructive cardiomyopathy, dilated cardiomyopathy with presystolic
      regurgitation and AV interval prolongation, and perhaps even in some patients
      with impairment of ventricular systolic function and substantial prolongation of
      the AV interval. Despite all that, optimization of the AV interval is not
      routinely performed because even the best available optimization procedures
      (stroke volume measurements at different AV intervals by aortic Doppler
      echography) is observer dependent, time-consuming and costly.

PMID- 9601862
TI  - [High-dose therapy of multiple myeloma with autologous hematopoietic stem cell
      transplantation and subsequent maintenance therapy with interferon alfa versus
      interferon alfa and dexamethasone--a randomized clinical study "4W"].

PMID- 9601863
TI  - [A Czech and Slovak interventional study of spirapril (the CASSIS study). A
      randomized, double-blind, multicenter, placebo-controlled study in chronic heart
      failure].
AB  - Spirapril, an ACE-inhibitor without the SH group was tested in a randomized
      double-blind multicentric study in patients with chronic symptomatic heart
      failure (NYHA II-IV). After a 1-4-week initial stage with placebo the patients
      were randomized into five groups: the first was given placebo, the second one
      spirapril 1.5 mg, the third one spirapril 3 mg, the fourth one spirapril 6 mg and
      the fifth one 5 and later 10 mg for a period of 12 weeks. The number of patients
      in different groups was in the following order: 48, 48, 53, 51 and 48. The
      condition for admission into the study was chronic heart failure not responding
      adequately to treatment with digoxin and diuretics, IHD or dilatation
      cardiomyopathy with the left ventricular ejection fraction (% tolerating a basic
      ergometric load for two minutes. The primary criterium was an increment during
      the period of the load, secondary criteria comprised objective and subjective
      cardiac symptoms, changes in the left ventricular ejection fraction,
      cardiothoracic index/heart size and quality of life. The load tolerance increased
      in all groups, however, no significant differences between groups were found. The
      authors also found regression of signs of pulmonary congestion during active
      spirapril treatment and diminution of the cardiac shadow. Moreover the authors
      proved a significant reduction of the mortality in the actively treated patients
      as compared with those receiving placebo, a lower frequency of hospital
      admissions and reduction of serious undesirable cardiovascular symptoms during
      active treatment. In patients with medium severe and severe cardiac failure with
      IHD, combination with short acting calcium channel blockers had an unfavourable
      effect on the load tolerance and clinical parameters. Sprirapril, combined with
      diuretics and digoxin is a suitable drug also in chronic cardiac failure.
      Questionable remains the importance of loading tests when verifying the
      effectiveness of ACE-inhibitors. Treatment with short-time acting calcium
      antagonists cannot be recommended in symptomatic chronic cardiac failure.

PMID- 9601864
TI  - [Therapy of heart failure with spirapril--the open phase of the CASSIS study.
      Analysis of the 2nd year extension of the CASSIS study].
AB  - The CASSIS study was a double-blind multicentric controlled Czech and Slovak
      study focused on treatment of chronic heart failure with the ACE inhibitor
      spirapril; it was conducted for 12 weeks. The present work analyzes the second
      year of the extended open part of the study when all patients (n = 168) were
      treated with 3 mg or 6 mg spirapril. A small proportion of the patients was
      treated with 12 mg spirapril. The objective of the study was to test the long
      term effectiveness and tolerance of spirapril. The general mortality was analyzed
      throughout the whole two-year period. The results revealed an unchanging total
      mortality, analyzed after three-month intervals, during the whole two-year
      period. Also the functional improvement of the patients according to NYHA which
      occurred after the first three months of treatment was preserved during the
      second year. Spirapril proved to be a well tolerated ACE-inhibitor. The authors
      did not observe angioneurotic oedema in any of the patients. Hypotension and
      cough were recorded in 0.6% of the patients. The incidence of undesirable
      laboratory effects was also low and the majority was due to the basic disease.
      Creatinine did not rise significantly and a rise of urea was observed only in a
      small number of patients. Liver functions and haemogram did not change during
      treatment. The results of the second year of erxtension indicate that spirapril
      is a very effective and safe ACE-inhibitor which will extend in a significant way
      therapeutic means in patients with chronic heart failure.

PMID- 9601865
TI  - [An invasive approach in patients with non-Q myocardial infarct. Yes or no?].
AB  - The objective of the presented retrospective work was to evaluate the expedience
      of general indication of an invasive procedure in patients with non-Q myocardial
      infarction (non-Q IM). The group is formed by 40 patients with non-Q IM, after a
      first coronary attack. The authors investigated the premorbid condition, the
      clinical course, early and late mortality, they evaluated the coronarographic
      findings of those who were subjected to angiographic examination and compared
      conservatively treated patients with those who had a revascularization operation.
      The results are in favour of an invasive procedure in all patients with a non
      transmural IM, in particular when the lesions are in the anterolateral area.

PMID- 9601866
TI  - [Cardiogenic shock in acute myocardial infarct].
AB  - Based on clinical records (three years) the authors assessed the characteristics
      of patients with cardiogenic shock during myocardial infarction (48 of 270
      patients with infarctions, i.e. 18%). The mortality of these patients was 77%.
      The incidence of cardiogenic shock evidently rose with age in both sexes and
      amounted to as much as 35% in the most advanced age groups. Other "risk factors"
      for the development of shock were arterial hypertension and diabetes. By dividing
      patients with myocardial infarction and cardiogenic shock into first infarctions
      (55%) and re-infarctions (45%) it was found that other risk factors for the
      development of cardiogenic shock are anterior localization of the infarction in
      first infarctions, and in re-infarctions it is in particular the number of
      previous infarctions (as they increase the size of the infarction focus). The
      authors point out that it is essential to pay increased attention to patients
      with acute infarction to prevent the development of cardiogenic shock (attempt
      thrombolytic treatment, treatment focused on prevention of ischaemia and
      arrhythmias). Apply also during its treatment thrombolysis or possibly PTCA.

PMID- 9601867
TI  - [The role of D-dimer determination in clinical evaluation with pulmonary
      perfusion scintigraphy].
AB  - The diagnosis of pulmonary embolism is even in contemporary clinical practice
      problematical. Pulmonary angiography is used in our departments very little due
      to its invasive character. The method of choice for diagnosis remains therefore
      perfusion scintigraphy of the lungs, in this country frequently without
      ventilation scintigraphy as it is not available in the majority of our
      departments of nuclear medicine. In recent years in the diagnostic algorithms
      also assessment of D-dimers was started, i.e. assessment of products of
      fibrinolysis assessed by monoclonal antibodies. The authors tried to find out how
      many patients admitted to the medical department for diagnosis of pulmonary
      embolization may have a false positive diagnosis on the basis of pulmonary
      scintigraphy. During the period III/96 to V/96 a total of 18 patients from the
      medical clinic with suspected pulmonary embolism were examined where the value of
      D-dimers(latex test) was assessed and at the same time perfusion scintigraphy was
      performed. With regard to the highly negative predictive value of D-dimer
      assessment the authors focused their attention on patients with a suspect or
      positive lung scan (i.e. treated on account of pulmonary embolism) while D-dimers
      were negative. Of 13 patients with suspect or possible pulmonary embolism, as
      assessed by scintigraphy, four had negative dimers(30%). With regard to the 90%
      reported negative predictive value, based on the literature, thus three of these
      patients were unnecessarily admitted to hospital and treated. The authors assume
      that assessment of D-dimers should be part of the examination protocol due to its
      non-pretentious character and low price as compared with costs of
      hospitalization.

PMID- 9601868
TI  - [The insulin resistance syndrome and fibrinolysis disorders].
AB  - The high atherogenic potential of the insulin resistance syndrome can be only
      partly explained by the association of "classical" risk factors of
      atherosclerosis which are considered part of it, i.e. impaired carbohydrate
      tolerance/diabetes mellitus type II, dyslipidaemia, hypertension and obesity.
      Impaired fibrinolysis due to excessive production of the plasminogen activator
      inhibitor-1 (PAI-1) are further risk factors which participate in the process of
      atherogenesis from the beginning of formation of the atheromatous plaque to the
      thrombotic occlusion of the vascular lumen. The authors present a group of 25
      patients with different grades of glucose resistance, evaluated by theinsulin
      response to a glucose load. The insulin resistant group (n = 15) differed
      significantly from the non-resistant one (n = 10) as regards body weight and the
      central type of obesity (< 0.01 and 0.001 resp.) insulin level on fasting and
      after a load (< 0.0001 and 0.001 resp.), triglyceride levels (< 0.01), the
      incidence of diabetes or impaired carbohydrate tolerance (66.7 vs. 20%) and
      hypertension (53.3 vs. 20%), but also as regards the PAI-1 activity (.0001). As
      regards blood sugar levels, total and HDL cholesterol the groups did not differ.
      The authors investigated also the relationship between PAI-1 activity and
      different components of the insulin resistance syndrome in the whole group. The
      closest correlation was found between the PAI-1 activity and the general
      insulinaemic response to a glucose load (< 0.001) and between PAI-1 and
      triglycerides (< 0.001). Based on the presented results it may be stated that
      hypofibnrinolysis as a result of excessive production of PAI.1 is part of the
      insulin resistance syndrome and potentiates its high atherogenic risk.

PMID- 9601869
TI  - [Kinetic analysis in the evaluation of glucose tolerance disorders. Evaluation
      and use of a new method in the diagnosis of glucose tolerance in clinical
      practice].
AB  - A kinetic model of oGTT has been used. This model is characterized by 7 glycaemia
      collections (0, 30, 45, 60, 120, 180 min). In some cases this is supplemented by
      determination of C-peptide and insulin values (0, 60, 120 min). This method is
      very simple and highly useful in clinical practice because it gives information
      about physiological stimulation by enterohormones, the first glucose passage
      through liver and next glucose utilization. The first part of the study deals
      with random error of the kinetic model of oGTT found by repeated calculations (>
      10,000 repeatings) of identical initial glycaemias in individual groups (DM, PGT,
      N). Random error of glucose clearance (the most suitable parameter) ranged within
      0.2 -2.1% in individual deviations. Then the identical calculations were made but
      loaded with glycaemia and with certain error in individual collection intervals
      (glycaemia 0.1, 0.2, 0.5 mmol/l; collection with 30, 60, 300 s). Random error of
      the method increased significantly with dispersion variance of glycaemias
      (maximum 17% with glucose clearance at glycaemia dispersion variance of 0.5
      mmol/l); changed time intervals less affected random error quantity. As
      acceptable and frequent deviation in practice was determined glycaemia dispersion
      variance of 0.2 mmol/l (corresponding to a total analytical error of glycaemia
      measurement) and dispersion variance of time intervals of 60 s. At these values,
      random error of the method increased maximally to 10.3%. Glucose has also a
      biological variability (not published yet for individual time intervals), the
      value of random error may be higher but will not achieve half of values of random
      error obtained at the classical oGTT. The second part of the study deals with
      comparison of both the tests (classical oGTT, kinetic curve of oGTT) in 126
      probands examined at metabolic and diabetologic out-patient department of the
      Hospital in Sternberk. It can be concluded that using a classical oGTT, 60% of
      patients were classified into incorrect groups as defined by dynamic results
      obtained by analysis of the kinetic model. Interesting enough is the fact that
      almost half of persons who cannot be classified by the classical oGTT had
      impaired glucose tolerance. Out of them, 15.6% had diabetes mellitus; almost 20%
      of normal patients also had impaired glucose tolerance. Over 1/5 of persons with
      impaired tolerance for glucose according to the classical oGTT was found by the
      kinetic model to have diabetes mellitus. On the contrary, 1/10 of diabetic
      patients diagnosed by oGTT had normal glucose clearance, over 1/2 of patients had
      only impaired glucose tolerance. Then in 126 persons random error of the method
      was again calculated (> 2,000 repeated calculations for each proband) amounting
      6.6%.

PMID- 9601870
TI  - [The effect of antioxidant therapy on indicators of activity of free radicals in
      workers exposed to risks of styrene].
AB  - To 30 workers exposed to the risk of styrene for a period of 30 days a mixture of
      antioxidants was administered: vitamin C 200 mg, vitamin E 300 mg, selenium 20
      mg, troxerutin 600 mg and beta-carotene 6 mg. Before the onset of supplementation
      and immediately afterwards laboratory indicators of antioxidant protection and
      lipid peroxidation were investigated. Before treatment workers exposed to the
      risk of styrene had a significantly higher malondialdehyde concentration (p <
      0.01) and antioxidant capacity (p < 0.01) as compared with the control group. Due
      to the established positive correlation between these parameters (r = 0.42, p <
      0.05) the findings can be evaluated as the result of increased exposure to free
      radicals. After supplementation a marked decline of the malondialdehyde
      concentration occurred p < 0.001) and a further rise of the antioxidant capacity
      (p < 0.001). The selenium concentration increased also markedly, the rise being
      more marked in subjects who had originally a lower concentration. There was a
      significant rise of uric acid which has an antioxidant effect (p < 0.01). The
      antioxidant enzymes superoxide dismutase and gluathione peroxidase did not change
      significantly. The results indicate the favourable effect of antioxidant
      treatment in subjects exposed to the risk of styrene.

PMID- 9601871
TI  - [A rheumatologic syndrome (paraneoplastic?) in benign tumors].
AB  - The authors discuss the possible development of rheumatoid paraneoplastic
      syndrome in patients with benign tumours. They present three observations they
      made (cardiac myxoma, subpleural lipoma and pulmonary fibrosclerotic
      pseudotumour). Paraneoplasias in these cases are interesting from the
      pathogenetic aspect as regards their development, possibly malignant
      transformation of benign intrathoracic tumours.

PMID- 9601872
TI  - [Disappearance of the sleep apnea syndrome in a female patient after surgery of a
      hypophyseal adenoma with acromegaly].
AB  - The association of the syndrome of sleep apnoea and acromegaly was described in
      the literature. However, so far no satisfactory explanation was given of the more
      frequent concomitant incidence of these diseases. The authors describe the
      disappearance of the sleep apnoea syndrome in a female patient after removal of
      an intrasellar microadenoma of the pituitary with overproduction of growth
      hormone.

PMID- 9601873
TI  - [Standards of diagnosis and therapy in arterial hypertension].

PMID- 9601874
TI  - [Oncopterin in clinical diagnosis].
AB  - In the submitted review the author presents hitherto published data on the new
      tumour marker oncopterin which was assessed in urine of patients with different
      types of tumours. Oncopterin is a derivative of endogenous pterins and
      trimethylene amine needed for the synthesis of polyamines which are synthetized
      specially in proliferating cells. Urinary oncopterin excretion can be assessed by
      high resolution liquid chromatography (HPLC). As test for the presence of
      malignant growth it seems to have a relatively high specificity.

PMID- 9601875
TI  - [Favorable effect of splenectomy on anemia in 3 siblings with type II congenital
      dyserythropoietic anemia (HEMPAS). (Ultrastructural changes in erythrocytes after
      splenectomy)].
AB  - Congenital dyserythropoietic anemia type II (CDA-type II) (HEMPAS) was reported
      in three siblings. CDA-type II was associated with marked hepatosplenomegaly and
      siderosis of both organs. All three sibling developed cholelithiasis with
      choledocholithiasis and obstructive jaundice in two of them. Anemia showing
      hemolytic component with sequestration of erythrocytes in the spleen was
      corrected after splenectomy without the need of blood transfusions during the
      follow up period of 20, 11 and 11 years. Ultrastructural investigation of the
      erythrocytes after splenectomy revealed increased number of erythrocytes showing
      the double membrane phenomenon.

PMID- 9601876
TI  - [The autoantibody profile and disease activity in patients with systemic lupus
      erythematosus].
AB  - Antinuclear antibodies are a group of autoantibodies which are typical for
      collagenous diseases. By means of the autoantibody profile different sub-groups
      of systemic lupus erythematosus (SLE) can be identified. This can serve as a
      certain prognostic factor of the affection. Patients with a negative antibody
      profile have fewer clinical and laboratory manifestations of SLE. Profile A (anti
      dsDNA and/or anti-Sm has, as compared with patients with a negative antibody
      profile, more frequent organ manifestations. Patients with profile B (anti-RNP)
      have a higher frequency of Raynaud's phenomenon. Profile C (anti-Ro, anti-La) is
      characterized in particular by photosensitivity of the skin and secondary
      Sjogren's syndrome. Profile D (antibodies against centromeres and/or Scl-70) are
      found in subjects with SLE with traits of scleroderma. Finally profile E
      (antibodies against histones) are found in SLE induced by drugs. In the submitted
      study in 28 patients with SLE autoantibodies anti-dsDNA, anti-DNP, extracted
      nuclear antibodies (ENA-Sm,Ro,La, histones, Sm/RNP, Scl-70) were evaluated and
      different subgroups of SLE were assessed. Attention was paid to their common
      characteristics and the activity of the disease. Associations of clinical
      activity of the disease expressed by the ECLAM index (European Consensus Lupus
      Activity Measurement) were tested as well as anti-dsDNA levels and also the
      association of the disease activity with C3 and C4 constituents of complement,
      CRP and circulating immunocomplexes in serum. Positivity of the antinuclear
      factor (ANF) was found in 21 patients, while in 7 subjects who were in clinical
      and laboratory remission, ANF was negative. A negative antibody profile was
      recorded in 9 patients, profile A was found in 13, 1 patient had profile B, and 4
      patients had profile C. Antibody profile D was not found in the group. When using
      regression analysis and Pearson s correlation coefficient, correlations were
      found between anti-dsDNA values and the system ECLAM (r = 0.72, p < 0.01), anti
      dsDNA and C3 levels (r = -0.59, p < 0.01), C4 (r = -0.50,, p < 0.01), and between
      the ECLAM system and C3 (r = -0.60, p 0.01) and C4 (r = -0.52, p < 0.01) and also
      between C3 and C4 mutually (r = 0.72, p < 0.01). From the submitted investigation
      ensues that investigation of antinuclear antibody levels in SLE is important not
      only for assessment of the diagnosis of the disease and its activity but also for
      assessment of the subgroups of the disease and for prediction of its development.
      As to other indicators of activity, assessment of the C3 and C4 constituents of
      complement is still important.

PMID- 9601877
TI  - [Antithrombin III in various conditions in internal medicine].
AB  - In a group of 993 patients with serious medical diseases an important deficiency
      of antithrombin III was found in patients with hepatic insufficiency, pulmonary
      embolism and with disseminated intravascular coagulation. Acquired antithrombin
      III deficiency in these conditions develops when the antithrombin production in
      the liver is low and also in patients with shock syndrome and disseminated
      intravascular coagulation. Assessment of antithrombin III is of diagnostic and
      prognostic value in thrombotic and prethrombotic conditions and its results is
      decisive for adequate substitution. Adequate AT III substitution without
      concurrent heparin administration in patients with septicaemia and manifestations
      of DIC improves the prognosis of patients with an increased endothelial
      resistance.

PMID- 9601878
TI  - [Endogenous erythropoietin in patients on regular dialysis therapy].
AB  - In a group of 66 patients with chronic renal failure having regular dialyzation
      treatment the serum concentration of endogenous erythropoietin (EPO), haemoglobin
      levels (Hb), haematocrit (Ht) and serum creatinine (Cr) were assessed. The
      examined subjects were never treated with recombinant erythropoietin and
      deficiency of iron, folic acid and vitamin B12 was ruled out. Endogenous EPO was
      assessed by the authors own RIA method, normal values being 24-42 mU/ml. The mean
      EPO concentration in the whole group of patients was 37.4 +/- 15.3 mU/ml, whereby
      12 patients had an EPO serum concentration higher than the upper range of normal
      values. Between EPO concentrations and Hb values a certain positive correlation
      was found (r = 0.42). A similar relationship was revealed also between EPO
      concentrations and Ht values (r = 0.41). Patients with EPO values higher than 42
      mU/ml had, as compared with the other patients, significantly higher values of
      erythrocytes (p .001). Statistical analysis did not reveal any relationship
      between EPO and Cr concentrations (r = -0.04). A low negative correlation was
      found between Cr and Hb values (r = -0.31) and between Cr and Ht values (r = 
      0.25). In the discussion the authors analyze the contemporary state of the
      problem of anaemia in chronic renal failure. Based on hitherto assembled
      knowledge they formulated the hypothesis ascribing considerable pathogenetic
      importance in the development of anemia to reduced sensitivity of bone marrow to
      EPO, probably as a result of retention of uraemic toxins and inhibitors of
      erythropoiesis. Inadequate EPO formation could be only a factor which makes it
      impossible for the developing anaemia to compensate and is due to an animpaired
      feedback at the level of recognition of the hypoxic signal.

PMID- 9601879
TI  - [Renal excretion of sodium in individuals with stabilized renal graft function].
AB  - In subjects with a transplanted kidney frequently tubular functions are impaired
      even when the glomerular filtration is within the normal range. In the present
      work the authors are dealing in more detail with the problem of tubular sodium
      reabsorption in the transplanted kidney. The purpose of the investigation was to
      assess to what extent these changes can be explained as the consequence of
      adaptational changes due to reduction of the number of nephrons and whether these
      changes have to be taken into consideration in the differential diagnosis of
      acute changes of graft function. The glomerular filtration rate (GF) was assessed
      on the basis of polyfructosan clearance, fractional sodium and potassium
      excretion (FENa and FEK) in a group of 12 subjects with a stabilized function of
      a transplanted kidney (group A), in 11 subjects after nephrectomy in healthy
      donors for transplantation (group B) and in 27 subjects after nephrectomy
      indicated for a pathological process in one kidney (group C). The mean values of
      GFR were as follows: Group A: 1.21 (+/- 0.19)ml/s/1.73 sq.m Group B: 1.19 (+/-
      0.17)ml/s/1.73 sq.m Group C: 1.24 (+/- 0.21)ml/s/1.73 sq.m The mean values of GFR
      in different groups did not differ significantly. The mean values of FENa in
      different groups were as follows: Group A: 3.02 (+/- 1.59)% Group B: 2.05 (+/-
      0.77)% Group C: 2.01 (+/- 1.17)% The mean value of FENa in group A was
      significantly higher than the mean value in group B (p < 0.01) and in group C (p
      < 0.01). The assembled findings support the idea that reduced tubular sodium
      reabsorption in the transplanted kidney (with a stabilized value of GFR) cannot
      be explained only as a manifestation of adaptation of tubular function as a
      result of the reduced number of functioning nephrons. The persisting osmotic
      sodium diuresis in the transplanted kidney must be viewed from the aspect of
      possibly impaired water preservation and the development of dehydration
      associated with a drop of GFR and must be differentiated from rejection.

PMID- 9601880
TI  - [The ergometry stress test in patients with stenosis of the left main coronary
      artery].
AB  - In 168 patients with ischaemic heart disease an ergometric loading test on a
      bicycle ergometer was made before coronarography. A total of 19 patients had on
      coronarography a finding of significant stenosis of the lumen of the trunk of the
      left coronary artery--group A. These patients were compared with a control group
      of 20 patients with confirmed coronary heart disease (narrowing of the diameter
      of the lumen by 50 or more percent) without affection of the trunk of the left
      coronary artery-group B. As to the investigated parameters of the ergometric test
      the two groups differed significantly in the total time of the load (group A:
      6.21 minutes, group B: 7.94 minutes, p < 0.05), while in all other parameters-
      total amount of performed work, sum of depressions of the ST segments during a
      maximum load, time of onset of stenocardias, time since development of 1 mm
      depressions of the ST segment, maximal depression of the ST segment in lead V5
      and number of leads with ST depressions above 1 mm--no significant difference was
      found. From the work ensues that from the ergometric loading test the finding of
      stenosis of the left coronary artery on coronarography cannot be predicted.

PMID- 9601881
TI  - [Accessory atrioventricular pathways with decremental conduction (Mahaim
      connections). 2 case reports].
AB  - The so called Mahaim connections form a relatively scarce variant of the
      preexcitation syndrome. Antidromic atrioventricular reentry tachycardia with wide
      QRS complex of LBBB morphology represents a typical clinical manifestation of the
      condition. Nodofascicular and nodoventricular fibres in all the probability do
      exist, but only rarely. Most of these accessory pathways are located on the firht
      free wall and conduct only antegradely and decrementally. Majority of these
      pathways are formed by long bundles inserting in the terminal part of the right
      bundle branch or in the myocardium near the right ventricular apex. In this
      setting traditional mapping strategy is of little use and different approaches
      must be employed. Only minority of these right-sided accessory pathways are short
      inserting in the ventricular myocardium under the tricuspid annulus. We present
      two case reports of patients with accessory connections exhibiting the so called
      Mahaim electrophysiology. In the first case, the pathway was merely an innocent
      bystander that, however, masked serious low intrahissian conduction disturbance.
      In the second case, the patient had a long-standing characteristic symptomatology
      due to the right anterolateral short accessory pathway which was successfully
      mapped and ablated.

PMID- 9601882
TI  - [Retrograde intravenous perfusion--a therapeutic method in trophic defects of the
      lower extremities. Experience in patients with primary thrombocythemia].
AB  - Retrograde intravenous perfusion (RIP), so-called Bier's blockade is a relatively
      new method of treatment of critical ischaemia of the extremities. It is based on
      the principle of retrograde, i.e. transvenous perfusion of the capillary
      circulation during which at the time of artificially discontinued circulation in
      the extremities a high concentration of effective substances in the target
      tissues is achieved. In addition to the mentioned critical ischaemia Bier's
      blockade can be successfully used in the treatment of so-called "diabetic foot".
      It is also possible to implement by this method a local medicamentously induced
      block of the sympathetic nerves by administration of Guanethidine. In patients
      with contraindications of systemic fibrinolytic treatment local thrombolysis can
      be made in phlebothromboses and acral vascular occlusions. In the treatment of
      tumours on the extremities, e.g. melanoblastome, it is possible to achieve by
      local administration of cytostatics comparable results, while the incidence of
      undesirable effects is smaller. The objective of the present work was to make the
      professional public familiar with this method. On the example of four patients
      with trophic defects of the lower extremities which developed as a result of
      primary thrombocythemia the application of Bier's method was demonstrated.

PMID- 9601883
TI  - [Detection of the Ki-ras mutation as a specific and sensitive marker of
      pancreatic carcinoma].
AB  - The authors describe the procedure used for assessment of a Ki-ras mutation as a
      specific and sensitive marker of carcinoma of the pancreas. The reliability of
      the method was tested in five patients with carcinoma of the pancreas.

PMID- 9601885
TI  - [Amanita poisoning and the importance of sorption hemoperfusion in its therapy].
AB  - Intoxications with poisonous mushrooms, in particular toadstools, are still a
      serious medical problem. The author presents contemporary views on the
      etiopathogenesis of intoxications with Amanita phalloides, the clinical picture
      of the phalloid syndrome and its prognosis. He emphasizes the importance of a
      comprehensive therapeutic approach, incl. the administration of antidotes
      (penicillin G and silibinin) and extracorporeal haemoelimination treatment. Early
      sorption haemoperfusion, either alone or combined with haemodialysis or
      plasmapheresis, prevent the development of hepatic and renal failure and
      significantly reduce the mortality from mushroom poisoning. The results of
      amanitine sorption in in vitro experiments and in the treatment of human
      intoxications justify the use of biocompatible synthetic resin sorbents
      (Amberlite XAD-2) in the treatment of mushroom poisoning rather than active
      charcoal.

PMID- 9601884
TI  - [Survival after accidental poisoning with a triple lethal dose of paraquat
      (Gramoxon)].
AB  - A case of a 22-year old man who accidentally poisoned himself with a triple
      lethal dose of organophosphate paraquat (commercially produced as Gramoxon).
      Owing to the quantity consumed and belated medical treatment, toxicologists
      initially considered the condition incurable but a complex therapy during a 52
      day hospitalization eventually saved the patients's life. Following is an
      analysis of the case a treatment survey and a discussion of mechanisms that
      possibly led to the successful result.

PMID- 9601886
TI  - [Fibrillary glomerulopathy].
AB  - The authors present an account on contemporary knowledge of the diagnosis and
      differential diagnosis of fibrillar glomerulopathies. The latter are
      characterized by extracellular localized microfibrils and microtubules resp. in
      the glomeruli of the kidneys, their diameter being 8-60 nm. They are divided into
      amyloid and non-amyloid types. The others are classified according to the
      immunofluorescent finding into immunoglobulin positive and negative ones. The
      differential diagnosis is important in particular in immunoglobulin positive ones
      as they are present in serious diseases such as cryoglobulinaemia, monoclonal
      gammapathy, systemic lupus erythematosus and immunotactoid glomerulopathy.

PMID- 9601887
TI  - [Bisphosphonates in the treatment of osteoporosis].
AB  - Bisphosphonates are chemical substances which are used in medicine for the
      diagnosis of bone diseases, for the treatment of bone metastases of various
      tumours and in recent years also for the treatment of osteoporosis, in particular
      postmenopausal or corticoid induced osteoporosis. The administration of
      biphosphonates is based on the idea that ideal treatment of an enhanced bone
      turnover is creation of a greater bone mass by de novo bone formation with
      concurrent inhibition of bone absorption (possibility of dismantling the
      remodelling cycle). This idea of the action of biphosphonates is based on the
      finding that they reduce the absorption activity of osteoclasts or enhance the
      osteoforming activity of osteoblasts. Biphosphonates thus create a positive
      balance of the remodelling cycle, i.e. they increase the density of bone mass and
      reduce the frequency of fractures. In the submitted paper the authors present a
      summary of results and possible use of these biphosphonate groups which were used
      in the treatment of involutional or corticoid induced osteoporosis.

PMID- 9601888
TI  - [Percutaneous transluminal angioplasty of the renal artery in transplanted
      kidneys].
AB  - The objective of the work was to evaluate the contribution of percutaneous
      transluminal angioplasty (PTA) to treatment of hypertension and the graft
      function of a transplanted kidney. Angioplasty of the graft artery was performed
      in 39 patients. Technical success rate: 85%. COMPLICATIONS: 13%--in particular
      during the first years after introduction of the method. Twenty seven patients
      were followed up on a long-term basis. Changes of the median arterial pressure
      (MAP) were evaluated as well as glomerular filtration (GF) assessed by creatinine
      clearance. Mean values: [table: see text] A statistically significant (p < 0.01)
      reduction of the median arterial pressure (drop by > 10 mm Hg) along with
      reduction of the number of antihypertensive drugs was recorded in 70% of the
      patients during the first year and in 80% kidney recipients in investigations
      extending beyond one year. A significant increase of glomerular filtration (by >
      20%) was found in 40% of the patients, on average the rise was insignificant.
      During the follow up period 13 kidney recipients were transferred to a
      dialyzation programme due to failure of the grafts as a result of rejection.
      CONCLUSION: Percutaneous transluminal angioplasty of a stenosis of the graft
      artery is the method of first choice in the treatment of hypertension. It is of
      fundamental importance also in rare cases in order to preserve or improve graft
      function and thus delay dialyzation treatment.

PMID- 9601889
TI  - [Personal experience in the diagnosis and monitoring of therapy in metabolic
      disorders with risk of crystallization in patients with recurrent urolithiasis].
AB  - A ten-year experience with diagnosis and therapy of metabolic abnormalities and
      crystallization risks in patients with recurrent urolithiasis is presented. Since
      1985, more than 900 persons with recurrent urolithiasis have been examined at the
      Metabolic Centre of the Hospital in Sternberk. The patients were examined
      routinely at ambulance or during hospitalization; the examination consisted of
      repeated urine and blood collections after the diet with various content of
      calcium and salt. All initial data (case history, physical finding, biochemistry,
      radiodiagnostics) were processed by a semi-expert computing program SOFT which
      was also used for monitoring of the therapy. Then the patients were divided into
      individual risk groups (Pak). Of all probands, the group of 130 patients
      (satisfying the strict criteria of the study) was selected and the data obtained
      was processed statistically. The group of 130 patients with recurrent
      urolithiasis (all of them were drug-treated) was compared to the group of 50
      individuals with urolithiasis treated by diet and regimen measures. The patients
      given drugs showed a significantly increased crystallization inhibitors
      concentration in urine and reduced crystallization promotors, or relative
      saturation of some lithiatic substances. The paper analyzes the effect of the
      mostly administered drugs on crystallization risks and some less known
      "metabolic" indications of application of some drugs are recommended. It is
      concluded that the dietary, drinking and regime measures are basic for a good
      therapy of patients with urolithiasis, but patients with recurrent urolithiasis
      should be applied a selective metaphylaxis of drugs after routine metabolic
      examination. This finding is supported by a low number of recurrent urolithiasis.

PMID- 9601890
TI  - [Thoracoscopic diagnosis of mediastinal lymphoma].
AB  - The possibilities of invasive diagnostic procedures and their place in
      examination schedule are evaluated in a group of 36 patients. Authors point out
      the need of close inter-discipline cooperation. They highly appreciate accuracy
      and reliability of mediastinoscopy and videothoracoscopy, on the other side they
      show possible complications and contraindications of these procedures.

PMID- 9601891
TI  - [Thallium perfusion scintigraphy and bicycle ergometry in the diagnosis of
      ischemic heart disease. Comparison with coronarography findings].
AB  - In 76 patients (66 men and 10 women, age 20-71 years) with stable angina pectoris
      planar thallium myocardial perfusion scintigraphy, bicycle ergometry and coronary
      angiography were performed. Thallium scintigraphy was highly sensitive (97%) for
      detection of ischaemic heart disease, the sensitivity of ergometry was 75%. When
      comparing patients with affected 1, 2 and 3 coronary arteries perfusion
      scintigraphy had a sensitivity of 100%, 90% and 100% resp., while bicycle
      ergometry 62%, 90% and 82% resp. The specificity of perfusion scintigraphy was
      low (47%), compared with ergometry (60%). The finding of s reversible perfusion
      defect during scintigraphy indicated significant affection of coronary arteries.
      The scintigraphic finding of diffuse myocardial ischaemic affection was not
      significant for assessment of the severity of the coronary artery disease.

PMID- 9601892
TI  - [Magnetic resonance in cardiology--a new alternative in noninvasive diagnosis].
AB  - The authors describe their initial experience with examination of the heart by
      magnetic resonance (MR) and discuss its position in the diagnostic algorithm of
      cardiac examinations:. They made 31 MR examinations of the heart in 30 patients.
      Echocardiography preceded 29 examinations. MR proved to be particularly useful
      where echocardiography did not lead to a decisive conclusion and called for
      confirmation by another method, or where it could not be carried out or its
      result was not consistent with the patient's clinical condition or the results of
      other examinations. The quality of the MR image was influenced most by the
      possibility of ECG gating. The latter was not possible in 16 patients (51.6%). In
      three of these (18.8%) the images were of such poor quality that they did not
      provide adequate diagnostic information. Images suitable for evaluation were
      obtained in 28 examinations (90.3%)--in these patients the MR information was
      valuable for establishment of the diagnosis. Magnetic resonance is a new possible
      method in the non-invasive diagnosis of heart disease. In the majority of cases
      it follows after echocardiographic examination which remains due to its
      accessibility the basic non-invasive method for examination of the heart.

PMID- 9601893
TI  - [Ischemic heart disease and bilirubin levels in a group of hospitalized
      patients].
AB  - During the last three years several papers were published, which found in large
      groups an inverse relationship between the bilirubin level and ischaemic heart
      disease. This relationship is typically U-shaped which means that with the rising
      bilirubin level the incidence of IHD declines but when the values are close to
      the upper normal range, the incidence of IHD rises again. This protective effect
      of bilirubin on the development of IHD is explained by the experimentally tested
      antioxidative action of bilirubin acting on LDL-cholesterol and thus inhibiting
      foam cell formation in the arterial wall. The authors decided to test this
      relationship in a group of their own 370 patients. They found that the
      relationship between the bilirubin level and IHD is U-shaped, however, that when
      the bilirubin levels are close to zero, the incidence of IHD is also low. The
      mean cholesterol levels did not correlate with the bilirubin level nor with the
      incidence of IHD. This phenomenon is interesting because it may in future open
      more comprehensive and more effective approaches to the prevention and treatment
      of atherosclerosis.

PMID- 9601894
TI  - [Plasminogen activator inhibitor (PAI-1) and diabetes mellitus. I. Regulation of
      PAI-1 levels].
AB  - Elevated PAI-1 levels were described in different insulin resistant conditions,
      incl. diabetes mellitus type II. In its formation probably several stimulating
      factors participate. Hitherto accomplished studies suggest not only the important
      effect of insulin acting synergically with very low density. lipoproteins (VLDL)
      on hepatocytes but also the importance of the endothelial pool where the action
      of proinsulin, VLDL and cytokines in synergy with Cai-dependent stimuli
      (oxidation stress, thrombin) is involved. Under certain circumstances also
      another adipocyte compartment may play a role, and a significant role of
      thrombocytes in raising the PAI-1 level cannot be ruled out either. A more
      detailed analysis of the raised PAI-1 level in different patients could extend
      the possibilities of therapeutic reduction of levels of this important risk
      factor of atherosclerosis.

PMID- 9601895
TI  - [High-dose chemotherapy--a new hope for some patients with malignant tumors?].
AB  - High-dosage chemotherapy is at present a very intensively investigated
      therapeutic procedure which rises great expectations. Administration of large
      doses of cytostatics is made possible by subsequent transplantation of autologous
      or allogenic haematopoietic progenitor cells (transplantation of peripheral stem
      cells or bone marrow). This reduces markedly the haematological toxicity of
      chemotherapy and it is possible to administer cytostatics in amounts at the non
      haematological toxicity borderline. In the first part of the paper theoretical
      principles of high-dosage chemotherapy are analyzed, the relationship between the
      dosage of the drug and its effect. The author describes also cytostatics used in
      regimens of high dosage chemotherapy and discusses general toxic effects of this
      treatment.

PMID- 9601896
TI  - [Prokinetic agents in the treatment of ulcer disease].

PMID- 9601897
TI  - Do barrier creams and gloves prevent or provoke contact dermatitis?
AB  - Barrier creams and gloves play an important role in the prevention of contact
      dermatitis, and various in vivo and in vitro methods have been developed to
      investigate their efficacy. However, their actual benefit in the workplace is
      still being debated. This article reviews both the benefits and adverse effects
      of barrier creams and gloves.

PMID- 9601898
TI  - Immunologic reactions triggered during irritant contact dermatitis.
AB  - This article discusses a novel approach to the understanding of human skin
      barrier function with particular emphasis on the immunologic consequences of
      barrier perturbation. Clearly, the most important homeostatic function of the
      skin is to restrict the ebb and flow of water molecules to maintain a
      physiological balance with respect to hydration between the inside of the body
      and the external environment. The early investigators of barrier function
      initially focused on defining the biophysical properties of the stratum corneum
      and integrating the concepts of Singer and Nicholson1 into various models such as
      the brick and mortar concept by Elias2 and the domain mosaic model by Forslind.3
      Rather than examining lipids, cholesterol, and free fatty acids in the stratum
      corneum, the authors have been interested in characterizing the types of
      specialized proteins termed cytokines that are intimately linked to the barrier
      structure and function of human and rodent skin.4 Cytokines are key mediators of
      inflammatory and immunologic reactions throughout the body; how these cytokines
      are modulated in response to changes in barrier function provides new insights
      that pass beyond the physical/mechanical protective nature of skin into the
      immunologic sphere of influence for barrier function and cutaneous homeostasis.

PMID- 9601899
TI  - In vitro and in vivo testing techniques for allergic contact dermatitis.
AB  - A variety of preclinical and clinical models have been developed for assessing
      the skin sensitization potential of chemicals. These models have been invaluable
      in identifying potential allergens and providing the information needed to
      conduct sound skin sensitization risk assessments. Of course, all models have
      inherent strengths and limitations. In the area of skin sensitization,
      significant advances have been made in understanding the underlying mechanisms of
      allergic contact dermatitis. This knowledge has been critical in the development
      of new in vitro and in vivo approaches for assessing the skin sensitization
      potential of chemicals. This article presents basic immunologic information that
      is being used to aid in the identification of cellular markers for
      differentiating irritant and allergic reactions in animals and humans. In
      addition, data are reviewed on the evaluation of skin equivalent cultures for the
      identification of skin allergens in vitro.

PMID- 9601900
TI  - Chemistry of contact allergens and irritants.
AB  - Understanding the nature and causes of contact dermatitis is as much a problem of
      chemistry as it is of biology. Many of the characteristics of an individual's
      reaction to a particular chemical, whether it be an irritant or allergen or both,
      depend very much on that person. From a more general perspective, however, the
      ability of a chemical to irritate and/or sensitize is a primary function of its
      chemical properties. The human biological system simply responds to the nature of
      the chemical perturbation it perceives; thus within the human population there is
      normal distribution in terms of the intensity of a reaction to a defined
      stimulus. This article reviews the present state of knowledge regarding the
      relationships between the ability of a chemical to cause contact dermatitis and
      its physicochemical properties, with close attention paid to how this knowledge
      may be used in a predictive sense to assist in risk assessment.

PMID- 9601901
TI  - Contact urticaria from xylene.
AB  - Xylene is widely used in medical technology, but there are many concerns about
      its safety. A 52-year-old woman, employed as a histotechnician, presented with
      burning, swollen hands. Patch testing and a visit to her place of work confirmed
      exposure and sensitivity, in the form of contact urticaria, to xylene. The use of
      xylene-resistant gloves resulted in clearing of the dermatitis. Establishing the
      diagnosis of contact urticaria from xylene allowed the patient to be cured of her
      dermatitis and continue working.

PMID- 9601902
TI  - Chloroxylenol causing hand dermatitis in a plumber.
AB  - Chloroxylenol use has increased and is found in many over-the-counter
      preparations. Although not a common sensitizer, chloroxylenol's role as a contact
      allergen and relevance, when positive patch tests are found, is often high. Pre
      patch test assessment generally does not identify chloroxylenol as a causative
      agent. It is increasingly found in liquid soaps particularly in industry and
      specifically in the health care environment. Even as a wash-off product, this
      allergen can be a hidden cause of allergic contact dermatitis.

PMID- 9601903
TI  - Newer cosmetic ingredients--new patch testing problems?

PMID- 9601904
TI  - Contact allergy to hydrocortisone and systemic contact dermatitis from
      prednisolone with tolerance of betamethasone.
AB  - BACKGROUND: Contact allergy to corticosteroids is not uncommon. As the clinical
      pattern that the patients exhibit may be misleading, the discovery at patch
      testing may be unexpected and solely a result of the fact that marker molecules
      for corticosteroid contact allergy are incorporated into standard series and that
      tests are read twice, on D3/4 and D7. OBJECTIVE: We describe a patient allergic
      to hydrocortisone who was given a cross-reacting corticosteroid, prednisolone,
      that led to a systemic contact dermatitis. The patient cleared when
      betamethasone, a non?Ncross-reacting corticosteroid, was administered. METHODS:
      The patient was patch tested to a standard series including tixocortol pivalate,
      and an extended corticosteroid series including betamethasone. RESULTS: Patch
      testing with tixocortol pivalate provoked an allergic patch test reaction (+? D3,
      +D7), whereas betamethasone did not. CONCLUSION: Our patient's allergy was
      undiagnosed for 5 years, and it was not until she was given a cross-reacting
      corticosteroid, which led to exacerbation of her dermatitis, that her physician
      suspected corticosteroid allergy. The incorporation of marker molecules for the
      detection of corticosteroid contact allergy into standard series with two reading
      occasions, 3 to 4 days apart, is advocated.

PMID- 9601905
TI  - Ethylenediamine hydrochloride versus amines in cutting oils.

PMID- 9601906
TI  - Contact dermatitis to foods and spices.
AB  - Cutaneous reactions to foods and spices occur in both the workplace and at home
      in those who grow, handle, prepare, or cook food. As spices are also used in
      cosmetics and perfumes other exposures are found. Several patterns have been
      described upon contact with food including irritant contact dermatitis, allergic
      contact dermatitis, contact urticaria, phototoxic contact dermatitis, and protein
      contact dermatitis. The purpose of this article is to review the approach to a
      patient suspected of having a cutaneous reaction to food or spices, as well as
      discuss these reactions and the allergens that cause them.

PMID- 9601907
TI  - Identification of risk products for fragrance contact allergy: a case-referent
      study based on patients' histories.
AB  - BACKGROUND: Fragrances are the first or second most common cause of contact
      allergy in dermatitis patients. OBJECTIVE: The aim of this study was to identify
      risk products for fragrance contact allergy. METHODS: The design was a case
      control study with a case group of 78 fragrance-mix-positive eczema patients and
      two control groups, one consisting of 1,279 subjects selected as a random sample
      of the general population and the other consisting of 806 fragrance-mix-negative
      eczema patients. The identification of risk products was based on the patients'
      histories of rash to scented products. Analysis of the associations between first
      time rash caused by different specified product categories and fragrance mix
      sensitivity was performed using logistic regression. RESULTS: It was found that
      first-time rash caused by deodorant sprays and/or perfumes were related to
      fragrance contact allergy in a comparison with both control groups. The risk
      (odds ratio) of being diagnosed as fragrance allergic was 2.3 to 2.9 greater in
      cases of a history of first-time rash to deodorant sprays and 3.3 to 3.4 greater
      in cases of a history of rash to perfumes than if no such history were present.
      First-time rash to cleansing agents, deodorant sticks, or hand lotions was also
      statistically significant but only in comparison with one of the control groups.
      CONCLUSION: Safety evaluation of fragrance materials used in perfumes and
      deodorant sprays should be performed with special attention.

PMID- 9601908
TI  - Corticosteroid contact hypersensitivity screening in Singapore.
AB  - BACKGROUND: Topical corticosteroids have been in use since 1957. Two percent to
      5% of patients attending patch test (PT) clinics have problems with
      corticosteroid contact hypersensitivity. Controversies abound with regard to the
      choice of steroids in the standard battery, the method of patch testing and
      reading, and the ideal concentration and vehicle. OBJECTIVE: To assess
      betamethasone 17-valerate (1% pet.), fluocinolone acetonide (0.25% petrolatum
      [pet.]), and tixocortol pivalate (1% pet.) used in the authors' standard battery.
      METHODS: Data were analyzed for patients seen between January 1994 and December
      1996 who had positive PT reactions to one or more of these steroids. RESULTS:
      3,603 patients had standard PTs, of which 20 had positive reactions to one or
      more of these steroids. There were three positive reactions to betamethasone 17
      valerate, 17 to tixocortol, and none to fluocinolone. On further patch testing to
      the authors' steroid battery, only one tixocortol-positive patient had a positive
      reaction to hydrocortisone (1% ethanol/ dimethyl sulfoxide [DMSO]). CONCLUSIONS:
      Corticosteroid allergy is found to be relatively uncommon in Singapore on the
      basis of this screening series. The frequency of negative reactions to
      fluocinolone acetonide is sufficiently low for this corticosteroid to be excluded
      from the authors standard series. The significance of positive tixocortol
      reactions remains unknown. From the review of other relevant literature, the
      authors recommend that budesonide be added to their present series. Testing
      betamethasone 17-valerate in 1% ethanol may yield more positive allergic
      reactions. Individuals with a positive allergic PT reaction to one corticosteroid
      should subsequently be tested to a full corticosteroid series.

PMID- 9601909
TI  - Six-hour versus 48-hour patch testing with varying concentrations of potassium
      dichromate.
AB  - This study examines the possibility of using patch contact times shorter in
      duration than the standard 48 hours. Using varying concentrations of potassium
      dichromate (K2Cr2O7), this study analyzed results from two sets of patches
      applied to the backs of 11 subjects for durations of 6 and 48 hours,
      respectively. Results showed that after the 48-hour application period, all
      subjects reacted to K2Cr2O7 at some concentration. For the patches applied for 6
      hours, 7 of the 11 subjects (64%) reacted to K2Cr2O7 at some concentration.
      Minimum elicitation thresholds (METs), the lowest concentration at which a
      reaction was observed, were established for both the 6-hour and 48-hour
      application times. The ratio of an individual's 6-hour MET to their 48-hour MET
      was calculated to evaluate the feasibility of patch testing with a higher
      concentration of an allergen for a shorter time period. Although the results
      clearly indicated that a higher concentration of allergen is required in order to
      elicit a reaction at 6 versus 48 hours, a fair amount of interindividual
      variability is exhibited by these 6-hour to 48-hour MET ratios. This observed
      variability would seem to preclude the use of 6-hour duration patch contact times
      for routine patch testing with K2Cr2O7.

PMID- 9601910
TI  - The incidence of allergic contact dermatitis in patients with psoriasis vulgaris.
AB  - BACKGROUND: Contact dermatitis is said to be rare in psoriasis patients, possibly
      because of accelerated epidermal turnover, the isomorphic (Koebner) response, and
      lymphocyte functional alterations. OBJECTIVE: To identify contact allergy in
      patients with psoriasis. METHODS: A written questionnaire was completed by 100
      patients with psoriasis about contact history, flare factors for psoriasis,
      topical skin care, medications, and occupational/hobby exposures. Of these
      patients, 20 agreed to be patch tested with a standard screening series (Hermal)
      and a 20-item psoriasis patch-test series that included ingredients that might be
      found in topical psoriasis products. RESULTS: Of the 100 patients, eight
      suspected a topical medication caused a reaction that worsened their psoriasis,
      29 gave a history of atopy, 11 reported reactions to metal jewelry, and 29
      reported an allergy to poison ivy. Patch-test results identified four of the 20
      patients with six positive patch tests to the materials tested: three of the six
      positive tests were interpreted as relevant to the patient's psoriasis (coal tar,
      ethylenediamine and dithranol), two patients tested positive to nickel and one to
      thimerosal. Five patients had irritant reactions to dithranol. CONCLUSIONS: In
      this small study, 20% of self-selected psoriasis patients had positive allergic
      reactions on patch testing. A screening contact and atopic history in psoriasis
      patients may help to identify a subset of patients who could benefit from a
      search for more relevant contact allergens with patch test evaluation. This could
      improve treatment strategies and possibly reduce disability.

PMID- 9601911
TI  - Rapid SPME/LC/MS/MS analysis of N-methylcarbamate pesticides in water.
AB  - Solid-phase microextraction combined with fast short-column liquid
      chromatography/electrospray ionization tandem mass spectrometry (SPME/LC/MS/MS)
      was used for isolating and analyzing nine N-methylcarbamate pesticides from water
      samples. Several SPME parameters, such as polarity of fibers, extraction time,
      and effect of ionic strength, were investigated and their impact on the
      SPME/LC/MS/MS technique was studied. The method was shown to be sensitive with
      detection limits between 0.3 and 1.9 microg/L and reproducible with precision
      between 4.5 and 12.7% RSD. The versatility of the method was exhibited by its
      excellent linearity in the concentration range of 2-2,000 microg/L in drinking
      water. A comparison of the SPME/LC/MS/MS method with LC/MS/MS methods utilizing
      traditional sample preparation techniques shows that the former offers similar
      performance in terms of precision and linearity, but is clearly easier to use and
      faster to perform.

PMID- 9601912
TI  - The influence of extraction procedure on ion concentrations in sediment pore
      water 
AB  - Sediment pore water has the potential to yield important information on sediment
      quality, but the influence of isolation procedures on the chemistry and toxicity
      are not completely known and consensus on methods used for the isolation from
      sediment has not been reached. To provide additional insight into the influence
      of collection procedures on pore water chemistry, anion (filtered only) and
      cation concentrations were measured in filtered and unfiltered pore water
      isolated from four sediments using three different procedures: dialysis,
      centrifugation, and vacuum. Peepers were constructed using 24-cell culture plates
      and cellulose membranes and vacuum extractors consisted of fused-glass air stones
      attached with airline tubing to 60-cc syringes. Centrifugation was accomplished
      at two speeds (2,500 and 10,000 g) for 30 min in a refrigerated centrifuge
      maintained at 4 degreesC. Only minor differences in chemical characteristics and
      cation and anion concentrations were found among the different collecting methods
      with differences being sediment-specific. Filtering of the pore water did not
      appreciably reduce major cation concentrations, but trace metals (Cu and Pb) were
      markedly reduced. Although the extraction methods evaluated produced pore waters
      of similar chemistries, the vacuum extractor provided the following advantages
      over the other methods: ease of extraction, volumes of pore water isolated,
      minimal preparation time, and least time required for extraction of pore water
      from multiple samples at one time.

PMID- 9601913
TI  - Effects of soil copper on black bindweed (Fallopia convolvulus) in the laboratory
      and in the field 
AB  - The present study aims to identify factors of importance to the extrapolation
      from laboratory toxicity test to field effects using copper and black bindweed as
      a model. In the laboratory the influence of Cu on seed germination and seedling
      survival was studied in both soil spiked with Cu in the laboratory and soil
      collected at a Cu-polluted site. Maternal effects were also studied. We found
      that seeds from Cu-stressed plants germinated more readily after a short, cold
      storage than control seeds, but no differences were found after a longer storage.
      The low germination of control seeds compared to maternal treated seeds could not
      be attributed to differences in thickness of the seed coat. Germination was
      slightly stimulated at 232 mg Cu kg-1. At the highest Cu level (i.e. 1,330 mg Cu
      kg-1) only 5% of the seeds germinated. Mortality of the seedlings increased with
      increasing Cu concentration reaching 40% at 391 mg Cu kg-1. At higher
      concentrations mortality decreased. Germination was not affected in laboratory
      tests with soil from a Cu-polluted site, but the biomass of the plants decreased
      with increasing Cu concentration. The distribution of the plants on a Cu-polluted
      site was registered in relation to soil Cu concentration. Cu was analyzed using
      three different extractors, i.e. HNO3, CaCl2, and DTPA. The distribution of the
      plant in the field was predicted from calculated lifetime effect of a given Cu
      soil concentration based on the laboratory tests. The results revealed that
      growth is more sensitive in the field than should be expected from laboratory
      tests due to several stressors in the former situation. Bioavailability was lower
      in the field soil but this was counteracted by the increased effect.
      Incorporating bioavailability in the prediction of field effects thus reduced the
      fit of the model and bioavailability measures could not be further evaluated.

PMID- 9601914
TI  - A laboratory assay to assess avoidance of contaminated sediments by the
      freshwater oligochaete lumbriculus variegatus 
AB  - Responses of benthic organisms to contaminated sediments in the laboratory
      historically have been assessed as survival, growth, and reproduction. However,
      these responses do not include behavioral aspects of organisms, which also can
      influence species distribution and abundance in benthic communities. This study
      documents avoidance behavior of the freshwater oligochaete Lumbriculus variegatus
      to contaminated sediments in the laboratory, utilizing a chamber specifically
      built to facilitate the measurement of this response. A number of field-collected
      sediments from sites with known contamination, several of which exhibited little
      or no toxicity in standard tests examining growth and/or survival, were
      evaluated. The oligochaetes exhibited marked avoidance to many of the sediments,
      indicating the potential utility of this assay in identifying effects of
      contaminated sediments on benthic community structure.

PMID- 9601915
TI  - Effects of copper and zinc on embryos and larvae of the horseshoe crab, limulus
      polyphemus 
AB  - We investigated the short-term and long-term effects of copper and zinc on
      horseshoe crab (Limulus polyphemus) embryos and first instar larvae from two
      estuaries in New Jersey, Delaware Bay and Sandy Hook Bay. Animals were exposed to
      nominal metal concentrations from 0.01 to 1,000 mg/L for 24 h, 48 h, 72 h, or
      continuously until the endpoint for the study (successful molting or death) was
      reached. Larvae showed greater tolerance of Cu and Zn than embryos. Under most
      treatment regimes, embryos and larvae were able to survive and molt in the
      presence of up to 100 mg/L Cu or Zn. Unexpectedly, horseshoe crabs from the more
      heavily polluted site (Sandy Hook Bay) were more susceptible to heavy metals than
      animals from a less polluted site (lower Delaware Bay). Horseshoe crab embryos
      and larvae were highly resistant to heavy metals in comparison to marine
      crustacea. The ability of Limulus embryos and larvae to survive in the presence
      of heavy metals implies the potential for these contaminants to be passed on to
      shorebirds and other predators.

PMID- 9601916
TI  - Developmental abnormalities in horseshoe crab embryos caused by exposure to heavy
      metals 
AB  - We examined the effects of heavy metals on the development of horseshoe crabs
      using bioassays in which embryos at different stages were exposed either
      continuously or for 24 h. Abnormalities included segment-defective embryos,
      double embryos, embryos with abnormal eye areas, and no-posterior embryos. In
      terms of their ability to affect normal development, the pollutants are ranked as
      follows: Hg >== organotin > Cr falling dots Cd > Cu > Pb > Zn. Organotin
      treatment was associated with a high frequency of abnormal eye embryos and Hg
      with segment-defective embryos. The specific cause of segment-defective
      malformations by Hg was investigated by using SH inhibitors and cytochalasin B,
      an inhibitor of microfilaments. These inhibitors induced Hg-type segment
      defective embryos; thus, Hg may also act by inhibiting SH-SS exchange and
      blocking morphogenetic movements. Horseshoe crab embryos from Delaware Bay and
      Sandy Hook Bay, New Jersey, were examined for developmental abnormalities.
      Malformed embryos were extremely rare (<0.6%) at five beaches along Delaware Bay
      as well as Sandy Hook Bay, suggesting that these horseshoe crab spawning areas
      are relatively unpolluted by heavy metals.

PMID- 9601917
TI  - Accumulation of tributyl- and triphenyltin compounds in Pacific oyster,
      Crassostrea gigas, from the Chinhae Bay System, Korea.
AB  - Butyl- and phenyltin residues were quantified in seawater and Pacific oyster
      (Crassostrea gigas) from the Chinhae Bay System, Korea. Butyltin compounds were
      detected in all the seawater and C. gigas samples, whereas phenyltin compounds
      were not detected in any seawater samples. Tributyltin (TBT) concentrations in
      seawater ranged <8-35 ng Sn L-1. TBT and triphenyltin (TPhT) concentrations in
      oysters ranged 95-885 and 155-678 ng Sn g-1, respectively. Spatial distribution
      of TBT was closely related to boating and dry-docking activities. However,
      spatial distribution of TPhT was not consistent with that of TBT. The estimated
      biological concentration factor (BCF) for TBT in C. gigas was about 25,000.
      Furthermore, 19 and 28% of total body burdens of TBT and TPhT were found in
      gonadal mass of C. gigas just prior to the spawning period, indicating that a
      proportional amount of TBT and TPhT would be released with a following
      reproductive process.

PMID- 9601918
TI  - Impact of guthion on survival and growth of the frog Pseudacris regilla and the
      salamanders Ambystoma gracile and Ambystoma maculatum.
AB  - The effects of the insecticides Guthion (technical grade) and Guthion 2S
      (commercial formulation) on survival and growth of tadpoles of the Pacific
      treefrog Pseudacris regilla, and larvae of the Northwestern salamander Ambystoma
      gracile and the spotted salamander Ambystoma maculatum were determined in
      continuous-flow exposures in the laboratory. Ninety-six-hour LC50 values were
      >3.6 mg/L for P. regilla with technical grade Guthion and 1.47 mg/L with the
      formulation Guthion 2S (measured as active ingredient Guthion). Ten-day LOAEL and
      NOAEL values based on length and weight for P. regilla with Guthion were 3.60 and
      0.98 mg/L. LOAEL and NOAEL values based on length and weight for P. regilla with
      Guthion 2S were 0.17 and 0.07 mg/L. The 96-h LC50 for Guthion 2S was 1.67 and
      1.90 mg/L for A. gracile and A. maculatum, respectively. LOAEL and NOAEL values
      based on length and weight for A. gracile with Guthion 2S were 0.22 and 0.10
      mg/L; they were 0.11 and 0.03 mg/L for A. maculatum based on weight. These
      species are as similar in sensitivity as some fish species but are more tolerant
      to Guthion than most invertebrates.

PMID- 9601919
TI  - The impact on reproduction of an orally administered mixture of selected PCBs in
      zebrafish (Danio rerio).
AB  - Zebrafish (Danio rerio) were orally exposed to a mixture of 20 PCBs in three
      different dose levels (0.008, 0.08, and 0.4 microg of each congener per gram of
      freeze-dried chironomids). Generally, the PCBs accumulated in a dose-related
      manner. After 13 weeks of exposure body, liver, and ovary weights, as well as the
      liver and ovary somatic index, were significantly lower in exposed groups. In
      addition, the PCB mixture was an effective inducer of hepatic EROD activity. The
      reproduction study performed with exposed females and unexposed males after 9
      weeks revealed that median survival time for larvae was only 7.7 days in the high
      dose group as compared with 14 days in controls. Furthermore, egg production was
      reduced in all three groups exposed. No differences in hatching frequency or
      median hatching time were recorded. Histologically, females in both the
      intermediate and high-dose groups contained a reduced number of mature oocytes.
      The present study demonstrates that the potency of the mixture of selected PCBs
      induces hepatic EROD activity and has a clearly negative effect on zebrafish
      reproduction.

PMID- 9601920
TI  - Biochemical composition, growth, and survival of the guppy, poecilia reticulata,
      during chronic sublethal exposure to cadmium 
AB  - The survival, growth, and biochemical composition (protein, total lipid, total
      carbohydrate, free reducing sugars, RNA, DNA) of the guppy, Poecilia reticulata,
      exposed to low sublethal concentrations of cadmium throughout its life cycle
      (beginning with 5-day-old juveniles) was studied. The purpose was to get some
      insight on the cause of metal toxic effects and evaluate the utility of
      monitoring levels of biomolecules as bioindicators of chronic toxicant effects on
      fish. The LC50 (48 h) of cadmium for 5-day-old Poecilia was 56.77 mg/L. The
      median lethal times (LT50) of Poecilia exposed to low cadmium concentrations (0.5
      5 mg/L) ranged from 7.65 to 72.51 days, and could be accurately predicted by the
      mortality observed after 20 days of exposure. The whole-body dry weight increase
      of cadmium-exposed guppies presented a decline from that of the controls. These
      declines were statistically significant after 20 days of exposure to
      concentrations higher than 1 mg/L and after 30 days to concentrations higher than
      0.5 mg/L. The percentage content in RNA was the only variable from the studied
      macrobiomolecules that significantly decreased when guppies were exposed to Cd
      concentrations higher than 0.5 mg/L for 30 days. The same trend was apparent in
      the ratio RNA/DNA. However, the ratio protein/RNA/DNA significantly increased
      after 10 days of growth to 1.5 mg/L and after 20 days to concentrations higher
      than 0.5 mg/L, thus having a predictive value for early-life history stages of
      Poecilia exposed to Cd.

PMID- 9601921
TI  - Occurrence of butyltin compounds in tissues of water birds and seaducks from the
      united states and canada 
AB  - Tributyltin and its breakdown products, mono- and di-butyltin, were determined in
      water birds collected from Lake Huron (the Great Lakes), marine coastal United
      States, and the west coast of British Columbia, Canada. Concentrations of
      butyltins in the liver of birds collected from Lake Huron were </= 27 ng/g, wet
      wt, whereas those from marine coastal areas contained up to 90 ng/g. Relatively
      higher concentrations were found in seaducks collected from coastal British
      Columbia, with concentrations as great as 1,100 ng/g. Mollusk-feeding seaducks
      seemed to accumulate greater concentrations of butyltins than predatory birds
      feeding on fish, other birds and small mammals. Hepatic concentration ranges of
      butyltins in birds from the United States and Canada were compared with those
      reported for the UK, Netherlands, Japan, and Poland. Exposure of birds to
      butyltin compounds continues to occur in harbors and marinas where TBT is used on
      vessels greater than 25 m in length.

PMID- 9601922
TI  - Lead concentration in the bones of the feral pigeons (Columba livia): sources of
      variation relating to body condition and death.
AB  - This paper reports on lead concentrations in the tarsometatarsi of 84 individuals
      of adult feral pigeons Columba livia found dead or experimentally captured in
      Bratislava, Slovakia. The interrelationships between lead concentrations and time
      of death, place of death, body measurements, sex, condition, and plumage
      phenotype were investigated. Size and shape of pigeons was not correlated with
      bone lead contamination. Sex and plumage color and pattern were slightly
      associated with variation in bone lead levels, females and melanic (urban)
      phenotypes tending to have higher bone lead concentrations than males and blue
      bar (wild) individuals. Birds with antibodies to chlamydiae did not contain
      significantly higher lead concentrations in the tarsometatarsi than birds without
      antibodies. Concentration of lead in tarsi was significantly higher in birds
      dying in winter, compared to birds dying at the end of summer. Chronic lead
      poisoning probably causes mortality in pigeons in winter. The natural stressor,
      cold weather, has the capability of exacerbating the effects of lead poisoning,
      and the mortality is due to lead exposure coupled with cold stress.

PMID- 9601923
TI  - Elemental profiles in feather samples from a mercury-contaminated lake in central
      california 
AB  - Flight feathers from six bird species at Clear Lake, CA were analyzed to
      determine the extent and distribution of mercury contamination from an abandoned
      mercury mine and associated levels of 14 other elements. Feather samples were
      collected from adult and juvenile osprey (Pandion haliaetus), including juvenile
      osprey from three additional comparison sites; adult western grebes (Aechmophorus
      occidentalis); adult great blue herons (Ardea herodias); adult mallards (Anas
      platyrhynchos); adult turkey vultures (Cathartes aura); and juvenile double
      crested cormorants (Phalacrocorax auritus). Samples were analyzed by a
      multielemental x-ray fluorescence method. The osprey from Clear Lake showed
      significantly elevated mercury concentrations relative to the comparison sites.
      Different species at Clear Lake had different mercury concentrations based on
      trophic status; osprey exhibited the highest mercury concentrations and the
      mallards showed the lowest. Lastly, we quantified differences in elemental
      concentrations, including mercury, between adult and juvenile osprey from Clear
      Lake. Elements known to be nutrients, such as sulfur and zinc, did not vary
      significantly among species or sites. Reproductive success of osprey at Clear
      Lake was monitored from 1992 to 1996 to determine if osprey reproduction was
      depressed. During this five-year period, the breeding population grew from 10 to
      20 nesting pairs and the average reproductive rate was 1.4 fledglings per nesting
      attempt. Although the osprey showed the highest mercury levels of any species
      sampled, their reproduction does not appear to be depressed.

PMID- 9601924
TI  - Aluminum and acid effects on calcium and phosphorus metabolism in young growing
      chickens (Gallus gallus domesticus) and mallard ducks (Anas platyrhynchos).
AB  - Acidification is associated with increased mortality, reduced growth, and bone
      abnormalities in birds. Associated with acid deposition is an increase in
      aluminum availability due to solubilization from soil and other sources.
      (Conversely, experimental diets containing aluminum sulfate have much reduced
      pHs.) The present studies compare the effects of two levels of dietary acid
      (sulfuric acid) (0.122 and 0.56 mol H+ per kg feed; 0.056 and 0.277 mol sulfate
      per kg feed) and dietary aluminum (aluminum sulfate at 0.1 and 0.5%; sulfate at
      0. 056 and 0.277 mol sulfate per kg feed) on bone growth, mineralization, and
      phosphorous/calcium homeostasis in growing birds (chickens and mallard ducks).
      Growth was reduced by the high acid (chicken) and aluminum (ducks and chickens)
      diets. A reduction in bone mineralization was observed in birds receiving
      aluminum-containing diets [low aluminum diet: decreased tibia ash, calcium, and
      phosphorus (chickens); high aluminum diet: decreased tibia dry weight, % of ash
      and mg; ash, calcium (chickens, ducks as % of ash), and phosphorus (chickens
      mg/duck, % of ash)]. Moreover, plasma concentrations of inorganic phosphate were
      reduced in chicks on the high aluminum diet. There were also marked decreases in
      bone growth and mineralization [tibia weight, ash (mg), calcium (mg), phosphorus
      (mg)] and plasma concentrations of 1,25-dihydroxy vitamin D3 in chicks on the
      high acid diet compared to those on a control diet. These changes were probably
      due to reduced feed intake; changes in bone indices being of a greater or similar
      magnitude in pairfed control. There was little change in bone indices, growth
      rate or feed consumption in ducklings receiving either the low or high acid
      diets. It is concluded that aluminum directly adversely affected bone
      mineralization whereas acid effects are mediated in part by changes in feed
      consumption.

PMID- 9601925
TI  - Metabolism and cytotoxicity of chlorpropham (CIPC) and its essential metabolites
      in isolated rat hepatocytes during a partial inhibition of sulphation and
      glucuronidation reactions: a comparative study.
AB  - The changes in metabolism and cytotoxicity of chlorpropham (CIPC) and its major
      metabolites, 4-hydroxychlorpropham (4-OH CIPC), 3-chloroaniline, and 3
      chloroacetanilide were investigated in isolated rat hepatocyte suspensions after
      a partial inhibition of sulphation and glucuronidation and the two reactions
      combined in an attempt to assess the part of each of them in the enhanced CIPC
      toxicity observed in vivo after D-galactosamine treatment. With sulphation and
      glucuronidation effective, CIPC has a cytolytic effect and reduces intracellular
      ATP and K+ level while 4-OH CIPC has a weak cytolytic effect but modifies ATP and
      K+ level in a greater extent than CIPC. Inhibition of sulphation does not affect
      the cytotoxicity of CIPC or 4-OH CIPC because there is a compensatory increase in
      the amount of 4-OH CIPC glucuronide formed and the level of free 4-OH CIPC always
      remain low. In contrast, when incubations are carried out with either CIPC or 4
      OH CIPC, the presence of D-galactosamine leads to a decrease of glucuronide and
      sulphate conjugates accompanied, respectively, by a 3.6-fold and 6. 9-fold
      increase of the free 4-OH CIPC level in the culture medium. This alteration of
      the metabolism is followed by a marked reduction of ATP synthesis with a
      concomitant modification of cell permeability. The cytolytic effect is due to
      CIPC itself, whereas the effect on energy supply was attributed to free 4-OH
      CIPC. The results demonstrate a combined effect of free 4-OH CIPC and D
      galactosamine on intracellular ATP level that could account for the partial
      inhibition of sulphation. This change in the CIPC metabolism could explain the
      increased CIPC toxicity observed in vivo after D-galactosamine pretreatment.

PMID- 9601926
TI  - Hepatic enzyme induction and acute endocrine effects of 2,3,3',4',6
      pentachlorobiphenyl in prepubertal female rats.
AB  - Polychlorinated biphenyls (PCBs) with the labile 2,3,6-substitution are important
      components of atmospheric and certain food chain exposures, but little is known
      about their biological activities. Chlorobiphenyl 110 (2,3,3',4',6-pentaCB) was
      investigated in weanling female rats dosed ip on days 21 and 22 and killed on day
      23 of age. The initial preparation of CB 110 markedly induced 7-ethoxyresorufin O
      dealkylase (EROD) activity and was found to be contaminated with coplanar
      3,3',4,4',5-pentaCB (CB 126). The contaminated preparation (CB 110C) was purified
      with activated charcoal (CB 110P). The CB 110P induced pentoxyresorufin O
      dealkylase (PROD), was weakly uterotropic and a modest depleter of serum
      thyroxine (T4). CB 110C caused increased liver weight, induced EROD, PROD, and
      UDP glucuronyl transferase activities and caused a greater depletion of serum T4;
      on the other hand, it suppressed the PROD induction and the uterotropic effect of
      CB 110P. Hepatic residues of CB 110 were a constant 2-3% of the dose while those
      of CB 126 (from CB 110C) increased with increasing dose to as much as 50% of the
      dose.

PMID- 9601927
TI  - Metabolic conversion of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) to 1,1
      dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) in the male F344/NCr Rat.
AB  - 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) and 1,1-dichloro-2, 2-bis(p
      chlorophenyl)ethylene (DDE) levels were measured by capillary gas chromatography
      with electron capture detection in liver and blood serum of male F344/NCr rats
      exposed for 2 weeks to DDD at dietary concentrations ranging from 8.51 ppm to
      2,000 ppm. DDD burdens in serum ranged from <0.006 microM (limit of detection) in
      control rats to 1.1 microM in the rats fed DDD at 2,000 ppm. The corresponding
      liver burdens in these animals ranged from <0.006 micromol/kg liver (controls) to
      11 micromol/kg liver in rats fed DDD at 2,000 ppm. Levels of DDE in serum or
      liver were undetectable (<0. 006 microM in serum; <0.006 micromol/kg liver) in
      rats fed control diet or diet containing 8.51 or 25.5 ppm DDD. The liver and
      serum burdens of DDE increased with dietary DDD concentration, reaching a maximum
      of 0.53 microM in serum and 4.7 micromol/kg liver in rats fed 2,000 ppm DDD. As a
      percentage of total DDD equivalents detected in liver or serum, the DDE burdens
      increased to a maximum of 36% and 31% in the serum and liver, respectively, of
      rats fed 689 ppm DDD. The possibility that the DDE might have been generated
      artifactually in the diet prior to administration to the rats was ruled out by
      analysis with capillary gas chromatography of the diet containing 2, 000 ppm DDD.
      The identification of DDE as a metabolite in liver extracts of rats fed 2,000 ppm
      DDD was confirmed with GC-MS. The results confirmed the presence of DDE as a
      metabolite of DDD.

PMID- 9601928
TI  - Radiation exposure and dose to small mammals in radon-rich soils.
AB  - Protection of the environment from radionuclide releases requires knowledge of
      the normal background levels of radiation exposure in the exposed biotic
      community and an estimate of the detriment caused by additional exposure. This
      study modeled the background exposure and dose to the lungs of small burrowing
      mammals from 222Rn in artificial burrows in radon-rich soils at a site in
      southeastern Manitoba. E-PERM chambers used to measure 222Rn in soil showed good
      reproducibility of measurement, with an average coefficient of variance (CV) of
      about 10%. Geometric mean (GM) 222Rn concentrations at nine randomly selected
      sites ranged from 5,490 Bq/m3 (GSD = 1.57, n = 7) to 41,000 Bq/m3 (GSD = 1.02, n
      = 5). Long-term monitoring of 222Rn concentrations in artificial burrows showed
      large variation within and between burrows and did not show consistent variation
      with season, orientation of the burrow opening, or levels of 226Ra in the soil.
      Annual GM concentrations in individual burrows ranged from 7,480 Bq/m3 (GSD =
      1.60) to 18,930 Bq/m3 (GSD = 1.81) in burrows several meters apart. A grand GM of
      9,990 Bq/m3 (GSD = 1.81, n = 214) was measured over the site for the year. An
      exposure model was constructed for five small mammal species based on their
      respiration rates and the number of hours spent in the burrow, active or
      hibernating, exposed to soil gas 222Rn, and the time spent out of the burrow
      exposed to atmospheric 222Rn. A background dose of 0.9 mGy/a from atmospheric
      222Rn (40 Bq/m3) was estimated for a large-bodied (80 kg), nonburrowing animal
      living on the soil surface. The highest exposures (mJ/a) in burrowing mammals
      occurred in those species with the highest respiration rates. Hibernation
      accounted for a small fraction of total annual exposure (<5%) because of very low
      respiration rates during this period. Absorbed dose to lung (mGy/a) was highest
      in the pocket gopher and decreased in the larger animals because of larger lung
      mass. Using mean 222Rn concentrations from the field studies and an equilibrium
      factor (F) of 0.5, doses to lung ranged from 90 mGy/a in the badger to 700 mGy/a
      in the pocket gopher. These doses closely correspond to those estimated from
      published dose conversion factors (DCFs) of 1.4 mGy per mJ . h/m3 for whole lung.
      For the ground squirrel, the DCF approach gives an estimated dose of 300 mGy/a
      versus 270 using the respiratory flow rate method. Based on these results, doses
      exceeding 500 mGy/a may be common in mammals and birds (i.e. the burrowing owl)
      living in radon-rich soils. Published risk coefficients for small mammals suggest
      that about 17 cancers would occur in 1,000 animals at these exposure rates.
      Although the potential effects from these exposures were not examined in this
      study, the study raises questions about how the animals may respond
      physiologically to this largely natural stress.

PMID- 9601929
TI  - Methyl sulphone metabolites of polychlorinated biphenyls (PCBs) in cetaceans from
      the Irish and the Aegean Seas.
AB  - The levels of PCBs and PCB methyl sulphone metabolites were determined in the
      blubber of six species of cetaceans that originated from the Irish Sea and the
      Aegean Sea (Mediterranean). Burdens ranging from 2.80 to 27.80 microg g-1 (lipid
      weight) total PCBs and 0.03 to 0.58 microg g-1 (lipid weight) total methyl
      sulphones were recorded. The highest cetacean methyl sulphone burden (0.58 microg
      g-1) was in an Irish Sea harbor porpoise (Phocoena phocoena). Methyl sulphone
      isomer formation capacity, as determined by PCB:MSF ratios, varied considerably
      between species as follows: harbour porpoise (1:10) > pilot whale (Globicephalus
      melas), white-sided dolphin (Lagenorhyncus acutus) (1:50) > common dolphin
      (Delphinus delphis), Risso's dolphin (Grampus griseus), and striped dolphin
      (Stenella coerueoalba), (1:100), and was related to interspecific variation in
      PCB methyl sulphone formation capacity.

PMID- 9601930
TI  - Reduction in human exposure to pesticide using traditional work clothing fabrics
      with chemical finishing: carboxymethylation and starch.
AB  - Franz diffusion experiments with human skin combined with work-clothing fabric
      have shown that skin exposure to pesticides is reduced by the presence of
      traditional nonbarrier textiles. This study was undertaken to obtain further
      information about the reduction in exposure using traditional work-clothing
      fabrics that had chemical finishing to increase the sorption properties. The
      effects of a renewable starch finish and chemical modification by
      carboxymethylation on cotton fabrics on the pesticide (methyl parathion)
      retention, transfer, and decontamination by laundering were investigated. Two
      weights of work clothing fabrics made of 100% cotton were used, one appropriate
      for shirts and the other for pants. The amount of pesticide observed on human
      skin was reduced by the presence of clothing fabric. Carboxymethylation of the
      shirt fabric reduced the amount of pesticide observed on the human skin. This
      treatment also resulted in less pesticide being transferred to a second fabric
      layer within a clothing system. No pesticide penetrated to the second fabric
      layer when the heavier pant fabric was used as the outer layer. The lighter
      weight shirt fabric did not retain as much pesticide as the pant fabric. The
      pesticide retained on the shirt fabric was increased by the application of a
      renewable starch finish and by carboxymethylation; both of these finishes were
      found to be effective in enhancing the decontamination of cotton fabrics by
      laundering.

PMID- 9601931
TI  - Determinants of polychlorinated biphenyl levels in plasma from 42-month-old
      children.
AB  - We report on the PCB levels in plasma from 42-month-old children and the factors
      that determine these levels. We measured the levels of the PCB congeners 118
      (2,4,5-3'4' pentachlorobiphenyl (CB)), 138 (2, 3,4-2'4'5'hexaCB), 153 (2,4,5
      2'4'5'hexaCB), and 180 (2,3,4, 5-2'4'5'heptaCB) in cord plasma, breast milk, and
      plasma from 42-month-old children (n = 126) living in the Groningen area, The
      Netherlands. The sum of the levels of these four congeners was calculated for
      cord plasma (SigmaPCBcord), breast milk (SigmaPCBmilk), and 42-month plasma
      (SigmaPCB42mo). SigmaPCBcord was used as a measure of prenatal exposure.
      Postnatal exposure was assessed in terms of the SigmaPCBmilk and the duration of
      lactation. In addition, maternal factors including age, body weight and height,
      parity, and formal education were recorded. In 42-month-old children who have
      been fully breast-fed for at least six weeks as babies, the median SigmaPCB42mo
      was 4.5 times as high as that in formula-fed children (0.81 microg/L vs. 0.18
      microg/L). The PCB levels in cord blood and human milk and the duration of breast
      feeding predict the plasma PCB level at 42 months. Each additional week of full
      breast-feeding is estimated to result in an increase of 0.3% of the milk PCB
      level. We concluded that lactation is a major source for the child's PCB body
      burden at 42 months.

PMID- 9601932
TI  - Chlororganic pesticides and polychlorinated biphenyls in breast tissue of women
      with benign and malignant breast disease.
AB  - Persistent chlorinated hydrocarbons assimilated through the diet may, as a result
      of their carcinogenic, immunotoxic, and, at least in regard to certain of these
      substances, estrogenic properties, play a role in the etiology of human breast
      cancer. As a consequence, increased concentrations of these ubiquitous
      environmental contaminants may be found in breast tissue of women suffering from
      malignant breast disease. To examine this possibility, surgically removed breast
      tissue samples from 65 women in Hesse, Germany were examined by capillary gas
      chromatography for p, p'-dichloro(diphenyl)trichloroethane (p,p'-DDT), p, p'
      dichloro(diphenyl)-dichloroethane (p,p'-DDD), p, p'
      dichloro(diphenyl)dichloroethene (p,p'-DDE), hexachlorobenzine (HCB), alpha-,
      beta-, and gamma-hexachlorocyclohexane (HCH) as well as the polychlorinated
      biphenyls (PCB) no. 28, 31, 49, 52, 101, 105, 118, 138, 153, 156, 170, and 180.
      Of the 65 patients, 45 were diagnosed with breast cancer. The control group of 20
      women suffered from benign breast disease such as mastopathy. After statistical
      adjustment for age differences, higher concentrations of p,p'-DDT, p, p'-DDE, HCB
      as well as PCB-congeners no. 118, 138, 153, and 180 were detected in tissue from
      women with breast cancer than in tissue from control persons. These differences
      were weakly significant for p, p'-DDE (p = 0.017), for PCB 118 (p = 0.042) and
      for PCB no. 153 barely not significant (p = 0.083). On an average, a 62% higher
      concentration of p,p'-DDE was found in cancer tissue (cancer patients: 805
      microg/kg fat; controls: 496 microg/kg fat) and 25% higher concentration of PCB
      no. 118 (81 microg/kg fat; 65 microg/kg fat). The concentrations of beta-HCH, PCB
      no. 156 and 170 were lower (not significant) in cancer tissue than in tissue from
      women with benign disease. PCB-congeners no. 105 and 149 as well as gamma-HCH
      could only be detected in individual tissue samples; congeners no. 28, 31, 49,
      52, and 101 as well as alpha-HCH and p,p'-DDD were not detected in any of the
      samples. To rule out the possibility that the concentrations of chlorinated
      hydrocarbons measured were influenced by the surgical procedure, 20 samples of
      tissue that were at a distance (minimum 1 cm and maximum 3 cm) from the tumor,
      tissue that was in direct proximity to the tumor (no more than 5 mm from the
      tumor), and tumor tissue itself (center of tumor) were separately prepared and
      analyzed. The average concentrations of chlorinated hydrocarbons varied to
      differing degrees and only minimally in tumor and surrounding breast tissue,
      indicating that the surgical procedure did not influence the results.

PMID- 9601933
TI  - Colon cancer mortality and total hardness levels in Taiwan's drinking water.
AB  - The possible association between the risk of colon cancer and hardness levels in
      drinking water from municipal supplies was investigated in a matched case-control
      study in Taiwan. All eligible colon cancer deaths (1,714 cases) of Taiwan
      residents from 1989 through 1993 were compared with deaths from other causes
      (1,714 controls) and the hardness levels of the drinking water used by these
      residents were determined. Data on water hardness throughout Taiwan have been
      collected from Taiwan Water Supply Corporation (TWSC). The control group
      consisted of people who died from other causes and the controls were pair matched
      to the cases by sex, year of birth, and year of death. The results show a
      significant negative relationship between drinking water hardness and colon
      cancer mortality. Odds ratio and 95% confidence intervals were 1.22 (1.04-1. 43)
      and 1.46 (1.22-1.75), respectively, for exposure to moderately hard water and
      soft water compared with the use of hard water. Trend analyses showed an
      increasing odds ratio for colon cancer with decreasing levels of hardness in
      drinking water. This is an important finding for the Taiwan water industry and
      human health.

PMID- 9601934
TI  - Atherosclerotic risks from chemicals: part I. Toxicological observations and
      mechanisms of atherosclerosis.
AB  - Atherosclerosis is a common disease, primarily of the large arteries, that begins
      in childhood and progresses with advancing age. Atherosclerosis leads to coronary
      heart disease, the major cause of death in the United States. Several risk
      factors affect atherosclerosis, but high LDL cholesterol is the most important
      risk factor. In addition, high levels of lipoprotein (a) appear to be associated
      with increased atherosclerosis and myocardial infarction. The level of
      lipoprotein (a) is genetically determined and is not affected by diet or
      exercise. Studies on the pathogenesis of atherosclerosis suggest that several
      steps are involved, including endothelial injury, increased arterial permeability
      to plasma lipoproteins, smooth muscle cell proliferation, and platelet
      aggregation. Atherosclerotic plaques are benign neoplasms of the arterial wall
      that result from the monoclonal proliferation of a single mutated smooth muscle
      cell. Abnormal proliferation of smooth muscle cells is the key event in the
      initiation and progression of atherosclerosis. Endothelial injury is another
      major contributory factor. Many factors associated with an increased risk of
      cancer are also associated with atherosclerosis. Cancer and atherosclerosis go
      through the same stages of initiation, promotion, and complication. Both
      inflammatory and immune reactions play important roles in the progressions of the
      two diseases. Smooth muscle cells and endothelial cells produce and respond to
      several cytokines and growth factors, which may influence the initiation,
      progression, and complication of the atherosclerotic lesions. Many studies have
      shown that the production of nitric oxide is decreased in atherosclerosis
      reduction in the bioavailability of nitric oxide in the arterial wall may lead to
      leukocyte adhesion and platelet aggregation. It should be noted additionally,
      nitric oxide is a mutagenic agent involved in the origin of neoplastic diseases.
      Atherosclerotic plaques express genes for products not found in the normal
      arterial wall. As with carcinogenesis, there may be more than one mechanism that
      promotes atherosclerotic lesions and there may be common mechanistic similarities
      between the two diseases. The purpose of this study is to establish an
      exploratory scientific hypothesis that will permit the use of standardized
      toxicological test data to evaluate different chemicals. The companion paper that
      follows will use a method of relative toxicological potencies to develop
      tentative risk coefficients based on relative potency. These papers, in
      combination, provide both a conceptual and a quantitative hypothesis that can be
      tested with data from forthcoming epidemiological studies or animal test models.

PMID- 9601935
TI  - Atherosclerotic risks from chemicals: part II. A RASH analysis of in vitro and in
      vivo bioassay data to evaluate 45 potentially hazardous compounds.
AB  - As reviewed in the Part I companion manuscript by Basavaraju and Jones (Arch
      Environ Contam Toxicol), atherosclerosis and carcinogenesis may share some common
      mechanisms of toxicological action. On that hypothesis, standardized test data
      taken from the Registry of Toxic Effects of Chemical Substances (RTECS) were used
      to compute relative potency factors for chemical compounds associated with
      increased risk of atherosclerosis to humans. Potencies of the different compounds
      were computed relative to each of six reference compounds comprised of
      benzo(a)pyrene, nicotine, cisplatin, adriamycin, estrogen, and 2,3,7,8
      tetrachlorodibenzo-p-dioxin. Reference-specific potencies were all converted to a
      common numerical scale adjusted to unit potency for B(a)P. Because the list of
      compounds contained several antibiotics, amino acids, hormones, chemotherapeutic
      agents, polynuclear aromatics, alkaloids, metals, and vitamins, the standardized
      estimates of potency varied significantly depending on which of the six reference
      compounds are considered as standards of comparison. For the n - 1 other
      substances. Estimates of relative potency, risk coefficients, and generalized
      risk equations are estimated for cigarette smoke condensate, dietary cholesterol,
      ethanol, and carbon disulfide. From data on atherosclerosis as a result of
      cigarette smoking, a tentative risk was estimated as Increased Relative Risk = S
      (mg/kg-day)-1 x dose (mg/kg-day) x RP, where the dose is chronic intake per
      kilogram of body weight per day, RP is the potency of the compound of interest
      relative to that of benzo(a)pyrene, and S is 0.83, 0.25, 0.20, or 13 depending on
      whether cigarette smoke, cholesterol, ethanol, or carbon disulfide
      epidemiological data were used as a standard of comparison.

PMID- 9601937
TI  - The NF-kappaB binding site is essential for transcriptional activation of the IL
      15 gene.
AB  - We cloned the 5' upstream region of IL-15 genomic DNA and examined promoter
      activity in macrophages stimulated with lipopolysaccharide(LPS). The 1.2 kilobase
      (kb) fragment of the 5' upstream region contained binding elements for LPS
      inducible transcription factors such as NFIL-6 or NF-kappaB. Determined by
      luciferase assay following transient transfection in the J774A.1 macrophage cell
      line, the 1.2 kb of the 5' upstream region exhibited high promoter activity in
      response to LPS, while promoter activity was significantly reduced by the 5'
      deletion of 313 base pairs containing the NF-kappaB binding motif. Nuclear
      protein prepared from LPS-stimulated macrophages formed a complex with the NF
      kappaB binding sequence of the IL-15 promoter. Taken together, the binding of
      nuclear protein to the NF-kappaB binding site is required for transcriptional
      activation of the IL-15 gene in LPS-stimulated macrophages.

PMID- 9601938
TI  - The natural history of an HLA haplotype and its recombinants.
AB  - The presence of haplotype-specific recombination sites can be determined by
      analyzing the conservation of extended haplotypes in the population. This
      approach considers all meioses in the history of the population and requires the
      presence of characteristic markers that easily allow the identification of the
      haplotype or of its recombined segments. The recombination breakpoint can then be
      mapped by looking for shared alleles between haplotypes selected through the
      specific marker/s. We identified a rare perfect tandem duplication of a 145 base
      pair segment in the LTA promoter, which tags a B60 (B60D) haplotype. The
      duplication was detected in 16/90 B60+ Europeans, while absent in 101 B60+
      Orientals. The conservation of the class I end and the extreme variability of the
      class II end suggested that the present-day B60D haplotypes originated from an
      ancestral haplotype by recombination events centromeric to the duplicated
      sequence. Through a fine mapping using markers of the HLA central region a
      preferential recombination site was localized in the 60 kilobase interval between
      TNFd,e, and D6S273/K11 Amicrosatellite loci (i.e., between LST1 and BAT3 genes).
      This site behaves as a potent recombination enhancer leading to fragmentation in
      most of the extant B60D haplotypes and can be considered responsible for their
      "instability". In the relatively recently founded Finnish population, where the
      LST1/BAT3 interval recombination has probably not yet had the chance to occur, a
      founder effect can explain the presence of a rare DP (DPB1(*)1601) allele in most
      B60D haplotypes in this population.

PMID- 9601939
TI  - Transcription and weak expression of HLA-DRB6: a gene with anomalies in exon 1
      and other regions.
AB  - HLA-DRB6 is one of the human major histocompatibility complex (MHC) genes present
      in DR1, DR2, and DR10 haplotypes (approximately 26% of individuals). It shows
      several anomalies in human and non-human primates, including exon 2 stop codons
      (non-randomly grouped between codons 74 and 94) and a promoter region, and an
      exon 1 coming from an inserted retrovirus. It has been shown that not only
      chimpanzee but also human Mhc-DRB6 lack the usual 3' untranslated (UT)
      polyadenylation signal, and in the present work it was found that the human DRB6
      gene coming from an HLA-DR2 haplotype is effectively transcribed after
      transfection in mouse L cells, and that HLA-DRB6 molecules may be expressed on
      the cell surface. DRB6 transcription level is remarkably lower in human than in
      chimpanzee. Moreover, their exons 1 (both taken from the 3'LTR region of a
      mammary tumor retrovirus) are also different; this shows that these viral
      insertions may be an important mechanism for different evolutionary changes in
      orthologous genes of different species. The pathways by which DRB6 molecules may
      be expressed on the membrane are unclear but other examples of truncated protein
      expression have also been described, even within the human major
      histocompatibility complex (i. e., in HLA-G). Finally, the presence of mature HLA
      DRB6 mRNA molecules supports the notion that splicing may take place even in the
      absence of a canonical 3'UT polyadenylation signal.

PMID- 9601940
TI  - Structural organization of rat CD1 typifies evolutionarily conserved CD1D class
      genes.
AB  - The non-major histocompatibility complex (MHC)-encoded CD1 family has recently
      emerged as a new antigen-presenting system that is distinct from either MHC class
      I or class II molecules. In the present study, we determined the genomic
      structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes,
      especially to CD1D1. The 5' flanking region of the CD1 gene contained the binding
      motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6.
      Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and
      the IFN response element) were absent. It is of interest that a tyrosine-based
      motif for endosomal localization found in the human CD1b cytoplasmic tail was
      encoded by a single short exon which was conserved in all CD1 molecules except
      for CD1a. Southern blot and direct sequencing analyses of inbred rat strains
      suggested very limited polymorphism in the 5' region where a hydrophobic ligand
      binding groove is encoded; a single base substitution resulted in amino acid
      alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the
      overall exon-intron organization of CD1 genes revealed that the length of the
      intron was also characteristic to each of the two classes of CD1 genes, classic
      CD1 and CD1D; such categorization has hitherto been made according to the
      sequence similarity of the coding region. This finding provides further support
      for the hypothesis that the two classes have different evolutionary histories. In
      contrast to the complete absence of the classic CD1 in rats and mice, the entire
      region of nonpolymorphic CD1D has been conserved through mammalian evolution.
      Similar functional properties of rodent CD1 and human CD1d are implied.

PMID- 9601941
TI  - KRC transcripts: identification of an unusual alternative splicing event.
AB  - Mouse KRC is a large zinc finger protein that binds to the kappaB motif of gene
      transcription and to the recognition signal sequences for the somatic
      recombination of the immunoglobulin and T-cell receptor gene segments. The mouse
      KRC gene is more than 70 kilobases (kb) in size, and contains at least seven
      exons, with the largest transcript being approximately 9.5 kb. Multiple
      differentially spliced transcripts of KRC were identified in thymus and brain,
      which would result in the production of multiple KRC protein isoforms with
      different N-termini and number of DNA binding domains. Alternative splicing
      events leading to the production of these multiple transcripts have been
      elucidated. Of particular interest are the exclusions in some transcripts of
      sequences from a gigantic exon of 5487 base pairs (bp), or from an exon of 176
      bp. Both potentially deleted exons code for zinc finger motifs that are essential
      components of the N-terminal and C-terminal DNA binding domains, respectively.
      Another intriguing phenomenon found in some KRC transcripts is the skipping of a
      459 bp fragment within the gigantic exon that would code for the N-terminal DNA
      binding domain. Bacterial fusion proteins derived from this fragment bind
      specifically to KRC target DNAs. Apparently, distinct alternative splicing events
      could eliminate the N-terminal DNA binding domain of KRC.

PMID- 9601942
TI  - A new apparently functional IGVK gene (VkLa) present in some individuals only.
AB  - We describe a hitherto unknown functional IGKV gene, VkLa, belonging to the IGKV1
      subgroup with exon 2 having only 94% similarity to the closest known IGKV gene, 1
      13/1D-13 (L4/L18a). Genomic DNA sequences spanning from 5' of the decanucleotide
      box to 3' of the heptamer (649 bp) were cloned and sequenced from four
      individuals. The new gene encodes the conserved amino acids in the exons and
      contains no apparent defects in known regulatory intron sequences such as pd-box,
      dc-box, TATA-box, CCCT-elements, splice-sequences, initiation codon, and heptamer
      sequence. VkLa is therefore potentially functional and, correspondingly, we found
      transcripts of properly rearranged VkLa with somatical hypermutations. VkLa was
      found in 12 of 57 (21%) healthy Caucasians by a nested polymerase chain reaction
      and subsequent sequencing of exon 2. This finding shows that there is more inter
      individual variation in the available IGKV gene repertoire than was hitherto
      assumed. Finally, we describe a minor correction in the IGKV1D-43 (L23) gene
      sequence.

PMID- 9601943
TI  - Intrachromosomal gene conversion frequency in the H2 differs between haplotypes.
AB  - We examined two intrachromosomal gene conversion events with a polymerase chain
      reaction assay at the DNA level between the two major histocompatibility complex
      class II genes Eb and Ab in mice sperm before selection has occurred. The
      frequency of the intrachromosomal gene conversion event between Ebd and Abd was
      found to be at least one order of magnitude higher than between Ebk and Abk in
      the same mice. Parental imprinting of the genes appears not to have an effect on
      gene conversion, as both (dxk)F1 and (kxd)F1 mice have indistinguishable
      frequencies in both haplotypes. The number of DNA copies of the donor and
      acceptor genes present in the cell at the time of mutation does not seem to
      influence the frequency of the intrachromosomal gene conversion in the k
      haplotype, whereas the frequency in the d haplotype is increased when double the
      number of donor and acceptor genes is present. The DNA fragment transferred
      between Ebd and Abd is invariably short, and need not comprise more than six
      nucleotides. The fragment transferred within the k haplotype varies in length,
      and can attain at least 100 nucleotides. The difference between the haplotypes
      both in length and frequency might be attributed to a six-nucleotide deletion in
      the Abk gene, which might make base-pairing between the genes less efficient and
      less precise.

PMID- 9601944
TI  - The Bw4/Bw6 difference between HLA-B*0802 and HLA-B*0801 changes the peptides
      endogenously bound and the stimulation of alloreactive T cells.
AB  - HLA-B*0801 is unique among HLA-B allotypes in having dominant amino acid anchors
      at positions 3 and 5 of the peptide-binding motif. HLA-B*0802 is a variant of HLA
      B*0801 in which the Bw6 sequence motif is replaced by a Bw4 sequence motif. This
      change, involving substitutions at positions 77, 80, 81, 82, and 83 of the B*08
      heavy chain, is probably the result of a single evolutionary event of
      interallelic conversion. Moreover, the difference between B*0802 and B*0801 is
      sufficient to stimulate a cytotoxic T-cell response. To assess further the
      functional impact of the Bw4 motif on a B8 background, we compared the peptide
      binding specificity of the B*0801 and B*0802 allotypes by sequencing the mixture
      of peptides endogenously bound to B*0802 and 12 individual peptides purified from
      that mixture. The HLA-B*0802 allotype, while able to bind some peptides bound by
      B*0801, has a broader repertoire of endogenously bound peptides than B*0801: the
      peptides bound by B*0802 are more variable in length and exhibit greater
      diversity in the carboxyl-terminal amino acid which interacts with the F pocket.

PMID- 9601945
TI  - New polymorphism of the human T-cell receptor AV28S1 gene segment.

PMID- 9601946
TI  - A new polymorphism in the promoter of the interleukin 5 receptor alpha subunit
      (IL-5RA) gene.

PMID- 9601947
TI  - Genomic organization and cDNA sequence of the rat RT1-DOb gene.

PMID- 9601948
TI  - Human IgM antibodies to tumor-associated gangliosides share VHIII (V3-23) and
      VKIV family subgroups.

PMID- 9601949
TI  - Structural organization, sequence analysis, and physical mapping of the Grc
      linked class Ib gene RT1.S3 in the rat.

PMID- 9601950
TI  - DNA sequence and structure of the mouse RING3 gene: identification of variant
      RING3 transcripts.

PMID- 9601951
TI  - An alternatively spliced form of the human CD94 gene.

PMID- 9601952
TI  - CT in vascular pathologies.
AB  - Since the introduction of helical scanners, CT angiography (CTA) has achieved an
      essential role in many vascular applications that were previously managed with
      conventional angiography. The performance of CTA is based on the accurate
      selection of collimation width, pitch, reconstruction spacing and scan delay,
      which must be modulated on the basis of the clinical issue. However, the major
      improvement of CT has been provided by the recent implementation of many post
      processing techniques, such as multiplanar reformatting, shaded surface display,
      maximum intensity projections, 3D perspectives of surface and volume rendering,
      which simulate virtual intravascular endoscopy. The integration of the
      potentialities of the scanner and of the image processing techniques permitted
      improvement of: (a) the evaluation of aneurysms, dissection and vascular
      anomalies involving the thoracic aorta; (b) carotid artery stenosis; (c)
      aneurysms of abdominal aorta; (d) renal artery stenosis; (e) follow-up of renal
      artery stenting; and (f) acute or chronic pulmonary embolism. Our experience has
      shown that the assessment of arterial pathologies with CTA requires the
      integration of 3D post-processing techniques in most applications.

PMID- 9601953
TI  - Intracranial vascular malformations.
AB  - Many efforts and much research have been dedicated to the field of non-invasive
      angiographic techniques in the past few years. Thanks first to magnetic resonance
      angiography (MRA) and subsequently to computed tomographic angiography (CTA),
      very interesting results have been obtained in the diagnosis of cerebrovascular
      diseases. Neck vessels are most successfully evaluated by both MRA and CTA, and
      the need for digital subtraction angiography (DSA) examinations in patients at
      risk for vascular occlusions has significantly decreased. The role and the
      diagnostic accuracy of these non-invasive modalities in intracranial vascular
      pathology is still under investigation, and several studies have been and are
      being performed. Both techniques have a better spatial resolution and sensitivity
      in detecting cerebrovascular malformations than DSA. In the diagnosis of cerebral
      aneurysms, both MRA and CTA - due to their high sensitivity - have become
      screening techniques in the population at risk for subarachnoid hemorrhage, these
      techniques may become basic diagnostic modalities in treatment planning. The
      results are less satisfying in the evaluation of brain arteriovenous
      malformations and in the different steps of pre- and post-therapeutic evaluation.

PMID- 9601954
TI  - Non-invasive assessment of neck-vessel pathology.
AB  - Clinical trials (NASCET, ECTS) have shown that carotid endarterectomy is
      protective against stroke in patients with symptomatic severe carotid stenosis.
      To decrease costs and risks, new diagnostic tools have been developed, such as
      duplex ultrasound (DUS), magnetic resonance angiography (MRA), and more recently
      computed tomography angiography (CTA). CTA and MRA provide excellent 3D
      angiography images of the extracranial vessels, using a volume-rendering
      technique. Digitally subtracted MRA (DSA-MRA) obtained with high-speed
      acquisitions during gadolinium injection has also recently become available.
      These techniques are changing the role of non-invasive assessment of carotid
      stenosis. Although it is probably too early to assess a definite diagnostic
      algorithm, the use of DSA as a pre-surgical tool for defining carotid stenosis is
      rapidly decreasing.

PMID- 9601955
TI  - Pulmonary circulation.
AB  - Evaluation of the pulmonary vasculature is mainly indicated in patients with
      suspected pulmonary thromboembolism. The routine procedure so far is ventilation
      perfusion scintigraphy alone or in combination with diagnostic assessment of the
      legs to rule out deep venous thrombosis. The results are still not reliable for
      the majority of patients. In the case of equivocal diagnosis, invasive
      conventional angiography is considered the gold standard. With steady
      improvements in tomographic imaging techniques, such as computed tomography (CT)
      or magnetic resonance imaging (MRI), non-invasive alternatives to the routine
      diagnostic work-up are given. Helical CT and CTA techniques are already in
      clinical use and estimated to sufficiently serve the demands for
      detection/exclusion of pulmonary thromboembolism. The disadvantages mainly
      concern peripheral disease and reconstruction artifacts. MRI and MR angiography
      have been implemented in the diagnosis of pulmonary vascular disease since the
      introduction of contrast-enhanced MRA. In breath-hold techniques, the entire lung
      vascularization can be delineated and thromboemboli can be detected. The clinical
      experience in this field is limited, but MRI has the potential to demonstrate its
      superiority over CT due to its improved delineation of the vascular periphery and
      the more comprehensive three-dimensional reconstruction.

PMID- 9601956
TI  - MRI of the breast: state of the art.
AB  - Contrast-enhanced MRI of the breast is probably the most sensitive method to
      detect breast pathology. It is best used to improve the sensitivity of
      mammography and sonography in selected patient groups with high breast cancer
      prevalence, where conventional methods are known to be less sensitive. Despite
      the high sensitivity of MRI, 5-12 % of invasive carcinomas are not recognized
      during MRI, because of lack of the typical criteria of carcinoma. MRI is probably
      inferior to mammography in detecting ductal in-situ carcinoma or very small
      carcinomas (< 3 mm), because the neo-angiogenesis induced by these small
      carcinomas is too faint to be detected by contrast-enhanced MRI. These tumours
      cannot be excluded by a normal MRI examination. MRI is non-specific as the
      distinction of benign and malignant breast lesions is unreliable. Only in
      selected cases (fat- or blood-containing lesions) may it improve the specificity
      of mammography and sonography. Mostly image-guided core biopsy is by far the most
      specific and least expensive method to establish a definitive diagnosis. For
      lesions exclusively detected by contrast-enhanced MRI, simple and reliable
      localisation devices are urgently needed. Presently accepted indications for MRI
      of the breast are: patients with silicone implants after mastectomy or
      augmentation mammoplasty (detection of recurrence/prosthesis rupture/silicon
      leakage); patients whose breasts are difficult to evaluate by combined
      mammography and sonography, who have had breast conservation therapy (local
      recurrence), or who have proven carcinoma in one breast (multifocality/
      centricity or contralateral breast carcinoma) or proven axillary lymph node
      metastases from an unknown primary tumor, especially when these are hormone
      receptor positive; patients with extensive postoperative scarring. In the future,
      genetically defined high breast cancer risk may become an indication.

PMID- 9601957
TI  - Multifunctional magnetic resonance imaging of cerebrovascular disease.
AB  - Over the last few years magnetic resonance imaging (MRI) has developed into a
      multipurpose imaging technique. In addition to anatomical information, data can
      be obtained on perfusion, metabolism and imaging of the vascular anatomy.
      Especially in the field of neuroradiology the possibilities for obtaining
      multifunctional information from combined MR examinations are promising. In
      particular, stroke or stroke-related research benefits from these developments.
      This article reviews the current status and the potential of newly developed MR
      techniques with regard to the intracranial hemodynamic changes in patients with
      severe stenosis or occlusion of the internal carotid artery. The combination of
      MR angiography, perfusion-weighted MRI and MR spectroscopic imaging seems
      especially useful in the management of the individual patient.

PMID- 9601958
TI  - Spiral CT angiography and surgical correlations in the evaluation of intracranial
      aneurysms.
AB  - We investigated the accuracy of spiral computed tomography angiography (CTA) in
      the detection and study of intracranial aneurysms by comparing CTA with selective
      angiograms and surgical findings. Twenty-six patients (9 men and 17 women; mean
      age 53.1 +/- 1.8 years) with suspected intracranial aneurysms were submitted to
      CTA (1- to 2-mm slices, pitch 1:1, 24 s, RI = 1) after a conventional CT
      examination showing subarachnoid hemorrhage (SAH) in 19 cases and during
      neuroradiological investigations performed for other reasons in 7 cases. One
      hundred twenty to 150 ml iodate contrast agent (0.3-0.4 gI/ml) were injected
      intravenously at 5 ml/s rate and with 12- to 25-s delay calculated with a
      preliminary test bolus. Three-dimensional shaded surface display (3D SSD) and
      maximum intensity projection (MIP) reconstructions were obtained from axial
      images. Then, within 48 h, all patients were submitted to digital subtraction
      angiography (DSA), with separate assessment of CTA and DSA findings. Twenty-two
      aneurysms shown by CTA were confirmed at DSA and surgery (true positives),
      whereas the vascular lesion was not confirmed at DSA in 2 cases (false
      positives). The presence of intracranial aneurysms was excluded at both CTA and
      subsequent DSA in 7 cases (true negatives) and there were no false negatives;
      sensitivity was 100 %, specificity 77.8 %, and diagnostic accuracy 93.5 %.
      Computed tomography angiography aneurysm location was confirmed at surgery in all
      cases, with very high accuracy in assessing the presence of an aneurysm neck (100
      %). Computed tomography angiography accurately depicted the aneurysm shape in 20
      of 22 cases, but failed to depict its multilobed nature in 2 cases. The mean
      aneurysm diameter calculated at CTA was 0.99 +/- 0.12 cm vs 1.09 +/- 0.11 cm at
      surgery (p < 0.01). The present results suggest that the high sensitivity of CTA,
      if confirmed by further studies, might help in avoiding having to resort to
      arteriography after negative CTA in SAH patients.

PMID- 9601959
TI  - Dural invasion of meningiomas adjacent to the tumor margin on Gd-DTPA-enhanced MR
      images: histopathologic correlation.
AB  - In intracranial meningiomas a flat, contrast-enhancing, dural structure adjacent
      to the tumor can occasionally be observed on gadolinium-DTPA-enhanced MR images.
      We wished to evaluate whether there is a correlation between MR images and
      meningeal invasion of intracranial meningiomas. The study included 54 patients
      with intracranial meningioma and the meningeal sign. MR studies included T2
      weighted and gadolinium-DTPA-enhanced T1-weighted images in axial, coronal, and
      sagittal planes. Histopathologic examinations were done on the meningiomas
      adjacent to the dura mater. The meningeal sign on MRI was observed from 2 up to
      35 mm from the main tumor mass in 31 (57 %) of the 54 patients. In 20 of these 31
      the histopathologic examination showed tumor invasion, while 11 patients had no
      tumor invasion but tissue proliferation, hypervascularity, and vascular
      dilatation. Seven of the 23 meningiomas without the meningeal sign had
      histologically proven infiltration of the adjacent dura. MR imaging is not able
      to determine definitive whether or not there is dural infiltration of the
      meningiomas. In conclusion, resection of the tumor with a wide margin is
      necessary to achieve complete excision of meningioma and to avoid recurrence.

PMID- 9601960
TI  - Toxic spongiform leucoencephalopathy after inhaling heroin vapour.
AB  - This is a report of clinical, CT and MRI findings in a patient with toxic
      spongiform leucoencephalopathy after heroin ingestion. The disease is observed in
      drug addicts who inhale pre-heated heroin. The clinical onset, which usually
      occurs some days or even longer after the last heroin consumption, is
      characterized by a cerebellar syndrome. The cerebellar hemispheres, the
      cerebellar and cerebral peduncles and the pyramidal tract may be affected.
      Spongiform demyelination is the morphological substrate of the lesions, which are
      not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The
      frequently perfect symmetry of the affection of functional systems points to a
      toxic and/or metabolic pathophysiological mechanism.

PMID- 9601961
TI  - Postoperative follow-up of juvenile nasopharyngeal angiofibromas: assessment by
      CT scan and MR imaging.
AB  - The purpose of this study was to assess the radiological findings after surgical
      removal of juvenile nasopharyngeal angiofibromas (JNA). The postoperative CT and
      MRI scans of ten patients were reviewed. The cured group included six patients.
      The non-controlled group included six patients with eight recurrences. Two
      patients belonged to both groups as they were also followed and cured after
      surgery for relapse. Four recurrences were asymptomatic and diagnosed by imaging.
      The imaging patterns were matched to the patients clinical status and endoscopic
      findings. In the cured group, non-enhanced residual soft tissue masses were seen
      in all cases. In the non-controlled group, recurrence was always demonstrated on
      early postoperative CT or MR as a dramatically enhanced mass. The recurrence was
      located in the lateral or superior aspect of the nasopharynx (n = 3), deep to the
      fossa of Rosenmuller (n = 4) or out of the nasopharynx (n = 1). In two cases a
      remaining enhanced mass disappeared spontaneously on iterated examinations.
      Because of numerous asymptomatic relapses, a radiological workup is recommended
      four months after surgery, even in patients with normal endoscopy, to rule out
      posterolateral or extranasopharyngeal recurrences. Spontaneous evolution of
      residual masses must be appreciated on iterated imaging examinations.

PMID- 9601962
TI  - Duplex Doppler analysis of interlobular arteries in transplanted kidneys.
AB  - The aim of our study was to analyze changes in spectral Doppler waveforms between
      interlobar and interlobular arteries in renal transplants and to determine
      whether sampling location at interlobular level can be suitable for intrarenal
      resistive index (RI) measurements. Paired series of spectral tracings from
      interlobar arteries and respective interlobular branches were obtained in 62
      consecutive renal transplants at 6.5-MHz Doppler frequency. The values of peak
      systolic velocity (PSV), end diastolic velocity (EDV) and RI were significantly
      (P < 0.01) reduced when calculated at interlobular level. In 38 % of cases, an
      interlobar RI higher than 0.70 corresponded to a normal interlobular RI. The
      values of PSV, EDV, and RI did not differ significantly at interlobular level
      between allograft subsets with normal and elevated serum creatinine level. Both
      intra- and interobserver variation were higher at interlobular than at interlobar
      level when performing the RI. During a conventional study of renal vasculature,
      an underestimation of abnormal RI findings can be expected from the incidental
      evaluation of interlobular tracings. We recommend sonologists to pay attention in
      accurately locating the sample volume at interlobar-arcuate level when evaluating
      intrarenal RI.

PMID- 9601963
TI  - Perineurioma (storiform perineurial fibroma) of the kidney in a child.
AB  - Perineurioma is an extremely rare benign tumor of the peripheral nervous system
      composed exclusively of perineurial cells. Imaging findings of this tumor are non
      specific and the diagnosis is based on histologic studies. We report a case of
      perineurioma of the kidney in a 7-year-old girl discovered incidentally during
      the evaluation of a urinary tract infection. This is the first case of renal
      perineurioma reported in a child. We present the ultrasound and computed
      tomography findings of this histologically confirmed neoplasm.

PMID- 9601964
TI  - Blunt abdominal trauma in adults: role of CT in the diagnosis and management of
      visceral injuries. Part 2: Gastrointestinal tract and retroperitoneal organs.
AB  - Computed tomography plays an important role in the detection and management of
      blunt visceral injuries in adults. Current standard examination techniques enable
      detection of the majority of perforating or devascularizing bowel injuries,
      although diagnostic findings are often subtle and meticulous inspection is
      required. Computed tomography may demonstrate pancreatic contusions and
      lacerations and help in distinguishing minor traumatic lesions without
      involvement of the pancreatic duct (organ injury scale, grades I and II) from
      deep lacerations with ductal involvement (grades III and V). Computed tomography
      enables distinguishing renal contusions and minor cortical lacerations that can
      usually be managed conservatively (injuries of grades I-III) from
      corticomedullary lacerations and injuries of the major renal vessels (grades IV
      and V) that have a less favorable prognosis and more commonly require surgical
      repair. In addition, CT is well suited for the detection of active renal
      hemorrhage and guidance of transcatheter embolization treatment and delineation
      of preexisting benign or malignant pathologies that may predispose to
      posttraumatic hemorrhage. The radiologist's awareness of the diagnostic CT
      findings of abdominal visceral injuries as well as their clinical and surgical
      implications are important prerequisites for optimal patient management.

PMID- 9601965
TI  - The pelvis after surgery and radio-chemotherapy for rectal cancer studied with Gd
      DTPA-enhanced fast dynamic MR imaging.
AB  - The aim of this work was to study the gadolinium-enhancement of malignant and
      benign pathology in the pelvis after surgery for rectal cancer. Thirty patients
      with either local recurrence (n = 17) or benign changes related to treatment for
      rectal cancer (n = 13) were studied with pelvic MR imaging. T2-weighted fast spin
      echo as well as T1-weighted spin- or gradient-echo imaging before and after
      intravenous contrast was performed and referred to as contrast-enhanced MRI
      (CEMRI). In addition, between the pre- and postcontrast images, dynamic contrast
      enhanced MRI (DCEMRI) was performed using a single-slice, multi-phase, contrast
      enhanced T1-weighted fast spoiled gradient-echo sequence. The time between the
      start of contrast injection to the beginning of enhancement, the duration and
      rate of enhancement as well as enhancement amplitude were recorded. The data were
      compared with the clinical diagnosis according to biopsy in 8 patients and
      surgery in 6 patients. In the remaining 16 patients, the clinical diagnosis was
      obtained by clinical or radiological follow-up. DCEMRI did not improve the
      diagnostic information compared with CEMRI. None of the examined parameters were
      found to help discriminating malignant from benign changes. Characterisation of
      lesions in the pelvis after rectal cancer surgery was not improved by a dynamic
      gadolinium-enhanced sequence.

PMID- 9601966
TI  - Biliary ascariasis associated with cholangiocarcinoma: ultrasonographic and
      percutaneous transhepatic cholangiographic findings.
AB  - The combination of biliary ascariasis and cholangiocarcinoma is rare. A 56-year
      old female presented with progressive jaundice. Ultrasonography revealed a
      curvilinear structure with anechoic center consistent with ascariasis within the
      dilated common bile duct. Ultrasonography also demonstrated that a slightly
      echogenic soft tissue mass projecting into the mid segment of the common bile
      duct proved to be coexistent cholangiocarcinoma. Percutaneous transhepatic
      cholangiography did not confirm the presence of worm. In this report
      ultrasonographic and percutaneous transhepatic cholangiographic findings of the
      case are described and the relative merits of these two techniques are discussed.

PMID- 9601967
TI  - Follow-up of musculoskeletal tumors. I. Local recurrence.
AB  - The prognosis for a patient with a musculoskeletal sarcoma has improved
      considerably over the past two decades largely due to the use of adjuvant
      chemotherapy. Surgical techniques have become more sophisticated with limb
      salvage, the preferred management in the majority of cases. Imaging plays an
      important role in the assessment of suspected local recurrence of tumor. This
      pictorial essay reviews the different imaging options and highlights various
      pitfalls in the detection and diagnosis of recurrence. The role of magnetic
      resonance imaging in this respect is stressed.

PMID- 9601968
TI  - The SAPHO syndrome: defining the radiologic spectrum of diseases comprising the
      syndrome.
AB  - The objective of our study was to clarify the radiologic spectrum of disease
      entities belonging to the SAPHO syndrome (SAPHO being an acronym for synovitis,
      acne, pustulosis, hyperostosis, and osteitis). A retrospective analysis of
      radiologic data was undertaken to determine the relationship of the
      osteoarthritic changes seen in palmoplantar pustulosis (PPP, n = 179), acne (n =
      3), psoriasis vulgaris (PsV, n = 355), generalized pustular psoriasis (GPP, n =
      25), and chronic recurrent multifocal osteomyelitis (CRMO, n = 4). Osseous
      changes of PPP, acne, and CRMO overlap each other; 7 PPP, 2 acne, and 3 CRMO
      patients manifested stenocostoclavicular hyperostosis as well as hyperostosis of
      the spine, pelvis, and/or femur. These findings were not seen in either PsV or
      GPP patients. Thirteen PsV and 4 GPP patients had peripheral arthritis and/or
      symmetrical sacroiliitis, which were not observed in the PPP, acne, and CRMO
      patients. The PPP, acne, and CRMO patients may be grouped as belonging to the
      single disease entity, namely SAPHO syndrome. Our findings do not support the
      inclusion of PsV and GPP in the spectrum of this syndrome.

PMID- 9601969
TI  - The bullhead sign: scintigraphic pattern of sternocostoclavicular hyperostosis
      and pustulotic arthroosteitis.
AB  - OBJECTIVE: The purpose of this retrospective study was to examine the value of
      whole-body nuclear medicine imaging and to evaluate the typical scintigraphic
      pattern of sternocostoclavicular hyperostosis (SCCH) and/or pustulotic
      arthroosteitis (PAO). In this entity the correct diagnosis is frequently missed
      because of uncharacteristic changes in other imaging modalities. MATERIALS AND
      METHODS: Forty-nine patients (age range 15-65 years old, mean age 36 years) with
      sternocostoclavicular hyperostosis (SCCH) and/or pustulotic arthroosteitis (PAO)
      were examined with whole-body scintigraphy and conventional radiography. RESULTS:
      Forty-three of 49 patients with SCCH/PAO showed a characteristic "bullhead"-like
      high tracer uptake of the sternocostoclavicular region with the manubrium sterni
      representing the upper skull and the inflamed sternoclavicular joints
      corresponding to the horns (= bullhead sign). Scintigraphy revealed additional
      skeletal manifestations (spondylitis, sacroiliitis, osteitis) in 33 of 49
      patients with SCCH and/or PAO. CONCLUSIONS: Bone scintigraphy is the imaging
      modality of choice for the diagnosis of skeletal involvement in PAO. Nuclear
      medicine reveals unexpected locations and shows the typical pattern of focal hot
      spots of the spine, sacroiliac joints and/or appendicular skeleton in the large
      majority of cases in combination with a bullhead-like tracer uptake of the
      sternocostoclavicular region. The bullhead sign is the typical and highly
      specific scintigraphic manifestation of SCCH and PAO in radionuclide bone scans
      and helps to avoid unnecessary biopsies.

PMID- 9601970
TI  - Alveolar soft part sarcoma.
AB  - We report a case of alveolar soft part sarcoma (ASPS) of the thigh with lung
      metastases in a 22-year-old woman. The findings of digital subtraction
      angiography (DSA) and MRI contributed to the diagnosis of ASPS. Especially
      dynamic contrast-enhanced MRI was useful for evaluating the effect of
      chemoembolotherapy.

PMID- 9601971
TI  - Imaging of the rotator cuff: an arthrographic pitfall.
AB  - We present a case where MRI and arthrography of the shoulder reports provided
      seemingly conflicting data. The subsequent findings at arthroscopy revealed a
      potential pitfall in arthrographic interpretation.

PMID- 9601972
TI  - MRI using hyperpolarized noble gases.
AB  - The aim of this study was to review the physical basis of MRI using
      hyperpolarized noble gases as well as the present status of preclinical and
      clinical applications. Non-radioactive noble gases with a nuclear spin 1/2 (He-3,
      Xe-129) can be hyperpolarized by optical pumping. Polarization is transferred
      from circularly polarized laser light to the noble-gas atoms via alkali-metal
      vapors (spin exchange) or metastable atoms (metastability exchange).
      Hyperpolarization results in a non-equilibrium polarization five orders of
      magnitude higher than the Boltzmann equilibrium compensating for the several 1000
      times lower density of noble gases as compared with liquid state hydrogen
      concentrations in tissue and allows for short imaging times. Hyperpolarization
      can be stored sufficiently long (3 h to 6 days) to allow for transport and
      application. Magnetic resonance systems require a broadband radio-frequency
      system - which is generally available for MR spectroscopy - and dedicated coils.
      The hyperpolarized gases are administered as inhalative "contrast agents"
      allowing for imaging of the airways and airspaces. Besides the known anesthetic
      effect of xenon, no adverse effects are observed in volunteers or patients. Pulse
      sequences are optimized to effectively use the non-renewable hyperpolarization
      before it decays or is destroyed, using fast low-flip-angles strategies to allow
      for dynamic/breath-hold imaging of highly diffusible (He) or soluble (Xe) gases
      with in vivo T1-times well below 1 min. Since helium is not absorbed in
      considerable amounts, its application is restricted to the lung. Xe-129 is also
      under investigation for imaging of white matter disease and functional studies of
      cerebral perfusion. Magnetic resonance imaging using hyperpolarized gases is
      emerging as a technical challenge and opportunity for the MR community.
      Preliminary experience suggests potential for functional imaging of pulmonary
      ventilation and cerebral perfusion.

PMID- 9601973
TI  - Spiral CT aortography: an efficient technique for the diagnosis of traumatic
      aortic injury.
AB  - The objective of this study was to assess the efficiency of spiral CT (SCT)
      aortography for diagnosing acute aortic lesions in blunt thoracic trauma
      patients. Between October 1992 and June 1997, 487 SCT scans of the chest were
      performed on blunt thoracic trauma patients. To assess aortic injury, the
      following SCT criteria were considered: hemomediastinum, peri-aortic hematoma,
      irregular aspect of the aortic wall, aortic pseudodiverticulum, intimal flap and
      traumatic dissection. Aortic injury was diagnosed on 14 SCT examinations (2.9 %),
      five of the patients having had an additional digital aortography that confirmed
      the aortic trauma. Twelve subjects underwent surgical repair of the thoracic
      aorta, which in all but one case confirmed the aortic injury. Two patients died
      before surgery from severe brain lesions. The aortic blunt lesions were confirmed
      at autopsy. According to the follow-up of the other 473 patients, we are aware of
      no false-negative SCT examination. Our limited series shows a sensitivity of 100
      % and specificity of 99.8 % of SCT aortography in the diagnosis of aortic injury.
      It is concluded that SCT aortagraphy is an accurate diagnostic method for the
      assessment of aortic injury in blunt thoracic trauma patients.

PMID- 9601974
TI  - Study of susceptibility-induced artefacts in GRASE with different echo train
      length.
AB  - The aim of this study was to evaluate the sensitivity of gradient-and-spin-echo
      (GRASE) sequences to susceptibility effects. GRASE sequences with 21 and 33
      echoes per echo train were compared with a T2-weighted FSE sequence with an echo
      train length of 5 by means of MRI in phantoms, volunteers (n = 10), and patients
      (n = 19) with old hemorrhagic brain lesions. All experiments were performed on a
      1.0-T clinical MR system (Impact Expert, Siemens AG, Erlangen, Germany) with
      constant imaging parameters. Contrast-to-noise ratios (CNRs) of tubes doped with
      iron oxides at different concentrations, of brain areas with physiological iron
      deposition (red nucleus, substantia nigra), and of areas of old brain hemorrhage
      were calculated for FSE and GRASE pulse sequences. Areas of old brain hemorrhage
      were also qualitatively analyzed for the degree of visible susceptibility effects
      by blinded reading. The CNR of iron oxide tubes and iron-containing brain areas
      decreased with increasing echo trains of GRASE sequences. The CNR of GRASE
      sequences decreased when compared with CNR of their FSE counterparts (GRASE 21
      echo trains 23.8 +/- 0.8, FSE 5 echo trains 26.7 +/- 0.9; p </= 0.01).
      Qualitative analysis confirmed these measurements. FSE with an ETL of 5
      demonstrated significantly stronger susceptibility effects than their GRASE
      counterpart with an ETL of 21. The results demonstrate that GRASE sequences do
      not necessarily compensate for the reduced sensitivity of FSE to susceptibility
      effects. The complex signal behavior of GRASE makes conventional SE, gradient
      echo, or FSE sequences containing shorter echo trains preferable when patients
      with intracranial hemorrhage are clinically evaluated.

PMID- 9601975
TI  - Comparative gene assignment in Ateles paniscus chamek (Platyrrhini, Primates) and
      man: association of three separate human syntenic groups and evolutionary
      considerations.
AB  - Regional assignment of eight markers to chromosome 2 of Ateles paniscus chamek
      (APC) confirmed a syntenic association similar to human (HSA) 12q + 14q + 15q.
      Three HSA 12q markers (RAP1B, PAH and ALDH2) were allocated to a shortest region
      of overlap (SRO) in APC 2p and found to be syntenic to other HSA 12q markers
      (PEPB and TCF1). Five HSA 14q markers (CTLA, PAX9, NSP, FOS and CHGA) were
      allocated to APC 2q and found to be syntenic to other HSA 14q markers (NP, TGM1,
      and CALM1) and to four HSA 15q markers (THBS1, B2M, HEXA and MPI) but dissociated
      from markers close to HSA 14qter (CKB) and HSA 15qter (FES-IDH2). Karyotypic
      comparisons showed an evident homoeology between APC 2p and HSA 12q while APC 2q
      was similar to an HSA 14qter::HSA 15qter fusion product. Comparative gene mapping
      data show that the HSA 14q + HSA 15q syntenic association is an ancestral
      mammalian gene cluster that has been maintained in several primate taxa.
      Conversely, in Ateles, it has been further associated with HSA 12q while, in
      Hominoids and Cebus, it has been independently dissociated into two separate
      syntenic groups, similar to HSA 14q and HSA 15q.

PMID- 9601976
TI  - Characterisation of the nucleolar organising regions during the cell cycle in two
      varieties of Petunia hybrida as visualised by fluorescence in situ hybridisation
      and silver staining.
AB  - The cell cycle-dependent spatial position, morphology and activity of the four
      nucleolar organising regions (NORs) of the Petunia hybrida cultivar Mitchell and
      the inbred line V26 have been analysed. Application of the silver staining
      technique and fluorescence in situ hybridisation on fixed root-tip material
      revealed that these interspecific hybrids possess four NORs of which only those
      of chromosome 2 are active during interphase, which implies that the NOR activity
      is not of parental origin. However, at the end of mitosis, activity of all NOR
      regions could be detected, suggesting that the high demand for ribosomes at this
      stage of the cell cycle requires temporal activity of all NORs. Using actin DNA
      probes as markers in fluorescence in situ hybridisation experiments enabled the
      identification of the individual petunia chromosomes.

PMID- 9601977
TI  - A specific conformation of the territory of chromosome 17 locates ERBB-2
      sequences to a DNase-hypersensitive domain at the nuclear periphery.
AB  - Chromatin in interphase nuclei exhibits a topology that is associated with the
      transcriptional state of cells. We examined the spatial, intranuclear
      distribution of chromosome 17 and the ERBB-2 (HER2/neu) sequence thereon,
      relative to that of DNase-hypersensitive chromatin (DHC), in breast tumour cells
      exhibiting different levels of expression of ERBB-2. These sequences were
      specifically associated with the nuclear periphery, within a band of DHC. The
      remainder of the chromosome 17 mass showed no preferential position within the
      nucleus. The peripheral placement of ERBB-2 sequences is associated with a
      specific conformation of chromosome 17. We propose that the conformational
      organization of chromosome territories might represent a fundamental control
      mechanism in gene expression.

PMID- 9601978
TI  - Repetitive arrays containing a housekeeping gene have altered polytene chromosome
      morphology in Drosophila.
AB  - Much of our understanding of gene and chromatin organization has been developed
      from observation of polytene chromosomes. We describe an experimental approach
      using transgenes that has allowed us to observe local changes in polytene
      morphology. A composite P transposon that contains a fusion between the
      regulatory region of Prat, a purine synthesis gene, and brown (bw), an eye
      pigment reporter, was transformed into the 65A10 polytene band and subjected to P
      transposase mutagenesis. Arrays of up to 320 kb at 65A10 were recovered by
      selection for increased pigment, and pigment levels were found to be proportional
      to numbers of copies. In polytene chromosomes, the original transformant was
      found to split 65A10 into two thin bands separated by an interband. With
      increases in copy number, the interband became progressively denser, eventually
      forming a dark, amorphous, deformable structure unlike any previously reported.
      The persistence of Prat expression in development, together with the cytological
      appearance of these large arrays, suggest that the state of the Prat promoter is
      affecting polytene structure. Because this unique structure is distinct from
      bands, interbands, puffs, and the chromocenter, which comprise polytene
      chromosomes, we suggest that it is composed of an altered form of chromatin.

PMID- 9601979
TI  - Replication timing properties across the pseudoautosomal region boundary and
      cytogenetic band boundaries on human distal Xp.
AB  - The establishment of human chromosomal regions as distinct and characteristic
      domains has been demonstrated by the reproducible banding patterns observed on
      metaphase chromosomes as a result of various staining techniques. Although the
      exact molecular properties responsible for the patterns are not well understood,
      a general correlation has been established between the time of replication of a
      particular region of DNA and its banding characteristics. Using a replication
      timing assay based on fluorescence in situ hybridization patterns, we
      investigated replication timing properties across chromosomal regions with
      potentially distinct chromatin properties. Relative replication timing values
      were determined using cosmid DNA probes around the pseudoautosomal region
      boundary in Xp22.3 and the cytogenetic band boundary regions surrounding Xp22.2.
      Although we observed replication timing domains that were generally consistent
      with cytogenetic banding patterns, we did not find sharp replication timing
      boundaries at either the pseudoautosomal region boundary or at the cytogenetic
      band boundaries.

PMID- 9601980
TI  - Ultrastructure of regions containing homologous loci in polytene chromosomes of
      Drosophila melanogaster and Drosophila subobscura.
AB  - We have used a new approach involving in situ hybridisation and electron
      microscopy to establish ultrastructural homologies between polytene chromosome
      regions of Drosophila melanogaster and Drosophila subobscura. Twelve probes were
      chosen to cover all the chromosomal elements: the myospheroid gene, the collagen
      type IV gene, the collagen-like gene, the w26 homeobox gene, the beta3 tubulin
      gene, the kinesin heavy chain gene, the tryptophan hydrolase gene, the Hsp82,
      Hsp22-26 and Hsp23-28, Hsp68, Hsp70 genes and the beta unit of the F0-F1 ATPase
      gene. Most of these loci were previously undescribed in D. subobscura and
      imprecisely located in D. melanogaster. We have demonstrated here, by an
      ultrastructural analysis of each chromosomal region, that homologous genetic loci
      tend to show a similar ultrastructure in the two species. With a few exceptions,
      the structural homology extends to the chromosomal regions surrounding the loci.
      In some cases, however, no structurally recognisable homology can be seen either
      in the locus or in its flanking regions.

PMID- 9601981
TI  - Genetic mapping of the amide response element(s) of the hsr omega locus of
      Drosophila melanogaster.
AB  - Small chromosomal deletions [Df(3R)eR-1 and Df(3R)eP] with intact hsromega
      transcription units but with variable deletions of the upstream region were used
      to map the upstream regions that regulate heat shock and amide responsivity of
      the 93D puff (hsromega locus) in salivary glands of late third instar larvae of
      Drosophila melanogaster. The Df(3R)eP deletion, generated by a P-element
      mobilization screen, removed the 93B6-7 to 93D3-5 cytogenetic region. [3H]uridine
      labeled transcription autoradiograms revealed that normal developmental and heat
      shock-induced expression of the 93D puff remained unaffected in both the
      deficiency chromosomes. However, the amide responsivity of the 93D site was lost
      on the Df(3R)eP homolog while the Df(3R)eR-1 homolog responded normally to
      amides. Southern hybridizations with a series of upstream probes mapped the
      distal breakpoint of the Df(3R)eP deletion between -22 kb and -23 kb of the
      hsromega transcription unit. Since the distal breakpoint of Df(3R)eR-1 is at
      about -45 kb upstream of the hsromega gene it is inferred that the amide response
      element(s) that modulate the specific transcriptional activation of the 93D puff
      following treatment of salivary glands with a variety of amides is/are located in
      the -22 kb to about -45 kb upstream interval. The Df(3R)eP and Df(3R)eR-1
      deletions also abolished dosage compensation at the 93D locus as well as the
      effect of beta-alanine levels on its heat shock inducibility.

PMID- 9601982
TI  - Telomeres and mechanisms of Robertsonian fusion.
AB  - The Robertsonian (Rb) fusion, a chromosome rearrangement involving centric fusion
      of two acro-(telo)centric chromosomes to form a single metacentric, is one of the
      most frequent events in mammalian karyotype evolution. Since one of the functions
      of telomeres is to preserve chromosome integrity, a prerequisite for the
      formation of Rb fusions should be either telomere loss or telomere inactivation.
      Possible mechanisms underlying the formation of various types of Rb fusion are
      discussed here. For example, Rb fusion in wild mice involves complete loss of p
      arm telomeres by chromosome breakage within minor satellite sequences. By
      contrast, interstitial telomeric sites are found in the pericentromeric regions
      of chromosomes originating from a number of vertebrate species, suggesting the
      occurrence of Rb-like fusion without loss of telomeres, a possibility consistent
      with some form of telomere inactivation. Finally, a recent study suggests that
      telomere shortening induced by the deletion of the telomerase RNA gene in the
      mouse germ-line leads to telomere loss and high frequencies of Rb fusion in mouse
      somatic cells. Thus, at least three mechanisms in mammalian cells lead to the
      formation of Rb fusions.

PMID- 9601984
TI  - Movements and stepwise fusion of endodermal precursor cells in leech.
AB  - At the four-cell stage, embryos of glossiphoniid leeches comprise identified
      blastomeres A, B, C and D. Subsequent cleavages of the A, B and C quadrants yield
      three large, yolk-rich endodermal precursor cells, macromeres A"', B"' and C"'.
      Eventually, these cells generate the epithelial lining of the gut via
      cellularization of a multinucleate syncytium. Meanwhile, cleavage in the D
      quadrant generates ten teloblasts that give rise to segmental mesoderm and
      ectoderm via stem cell divisions. Here we show that, during cleavage, macromeres
      A"', B"' and C"' shift clockwise relative to the D quadrant, while C"' comes to
      envelop the nascent teloblasts. During gastrulation, derivatives of the
      teloblasts undergo epibolic movements over the surface of the A"', B"' and C"'
      macromeres to form the germinal plate, from which segmental tissues arise. We
      find that the three macromeres fuse in a stepwise manner to initiate formation of
      the multinucleate syncytium; cell C"' fuses about 25 h after the fusion of A"'
      and B"', and the teloblasts fuse with the macromere-derived syncytium later
      still. When macromeres are biochemically arrested by microinjecting them with the
      A chain of ricin, a further difference among the macromeres is revealed.
      Biochemical arrest of A"' or B"' slightly retards the rate of germinal plate
      formation, but arrest of C"' frequently accelerates this process.

PMID- 9601985
TI  - Reduced expression of pax-3 is associated with overexpression of cdc46 in the
      mouse embryo.
AB  - CDC46/MCM5 encodes a protein that is highly conserved among yeast, plants, and
      animals. It is found in a complex which exhibits DNA replication licensing
      activity, which is proposed to regulate the synthesis of DNA once and only once
      per cell cycle. In yeast, loss of function mutations of CDC46/MCM5 decrease DNA
      synthesis. Very little is known about the regulation of CDC46/MCM5 in any
      species. We report here that, in the mouse embryo, expression of cdc46 is
      increased in unfused portions of the neural tube when the gene encoding the
      transcription factor, Pax-3, is either nonfunctional or underexpressed. These
      results were observed both in embryos of diabetic mice, which we have previously
      shown express significantly reduced levels of Pax-3 mRNA, and in Splotch embryos,
      which carry loss of function Pax-3 alleles. This indicates that expression of
      cdc46 is negatively regulated as part of a Pax-3-dependent pathway. Since cdc46
      appears to regulate DNA synthesis and cell cycle progression, it is possible that
      its overexpression is involved in defective embryonic development that is
      associated with loss of Pax-3 function.

PMID- 9601986
TI  - Shell differentiation and engrailed expression in the Ilyanassa embryo.
AB  - We have used in situ hybridization and immunocytochemistry to study the
      expression of the engrailed-related gene, Ily-en in embryos of the marine mud
      snail Ilyanassa obsoleta. We find that Ily-en is only expressed in shell gland
      cells. Only mRNAs localized in the shell gland hybridize to an antisense probe of
      the Ily-en homeobox. Similarly, only shell gland cells or shell-forming cells are
      stained by the monoclonal antibody 4D9, which was raised to the engrailed-class
      protein from Drosophila. Ilyanassa embryos made deficient in vegetal cytoplasm by
      removing the third polar lobe fail to differentiate an organized external shell.
      They do however make some randomly oriented internal shell fragments in which Ily
      en is expressed. Because Ily-en is expressed in shell gland cells of both normal
      and lobeless embryos, we conclude that the determinant(s) required for Ily-en
      expression are not exclusively localized in the polar lobe.

PMID- 9601987
TI  - Molecular evidence for the gnathobasic derivation of arthropod mandibles and for
      the appendicular origin of the labrum and other structures.
AB  - Mandibles are feeding appendages functioning as "jaws" in the arthropod groups in
      which they occur. Which part of this appendage is involved in food manipulation
      (limb tip versus limb base), has been used to suggest phylogenetic relationships
      among some of the major taxa of arthropods (myriapods, crustaceans, and insects).
      As a way to independently verify the conclusions drawn from previous
      morphological analyses, we have studied the expression pattern of the gene Distal
      less (Dll), which specifies the distal part of appendages. Our results show, in
      contrast to the traditional view, that both insect and crustacean adult mandibles
      are gnathobasic, handling food with the basal portion of the appendage.
      Furthermore, as is evident by the reduction in the number of Dll-expressing cells
      in the later developmental stages, adult diplopod jaws are also gnathobasic.
      Thus, jaws of all mandibulates (myriapods, crustaceans, and insects) seem to have
      a similar gnathobasic structure. We have also found that Dll is expressed in the
      labra of all arthropod taxa examined, suggesting that this structure is of
      appendicular derivation. Additionally, the spinnerets and book lungs of spiders,
      long considered on other grounds to be modified appendages, express Dll,
      confirming this interpretation. This study shows that, in addition to their use
      in phylogenetic and population genetic studies, molecular markers can be very
      useful for inferring the origins of a particular morphological feature.

PMID- 9601988
TI  - Quantity of prelocalized maternal factor is associated with the timing of
      initiation of an epidermis-specific gene expression of the ascidian embryo.
AB  - We produced half-egg-volume ascidian embryos by dividing the unfertilized egg of
      Halocynthia roretzi at the equatorial plane, and investigated the timing of the
      initiation of the expression of three tissue-specific genes, a muscle-specific
      actin gene HrMA4, a notochord-specific gene As-T and an epidermis-specific gene
      HrEpiC in the half-egg-volume embryos of the animal side and those of the vegetal
      side. The timing of the onset of HrMA4 and As-T expression in both the animal-
      and vegetal-half embryos and that of HrEpiC expression in the animal-half embryos
      were essentially the same as that of normal embryos. In contrast, the timing of
      HrEpiC expression in the vegetal-half embryos was delayed by one division cycle
      compared with the normal embryos. This delay was partially recovered by
      increasing the amount of unfertilized egg cytoplasm of the animal hemisphere,
      suggesting that the timing of HrEpiC expression is regulated by the amount of a
      maternal factor which is distributed abundantly in the animal hemisphere of the
      unfertilized egg.

PMID- 9601989
TI  - Inhibition of mesoderm formation by follistatin.
AB  - Mesoderm induction requires interaction between cells of the animal and vegetal
      hemispheres of the embryo. Several molecules have been proposed as candidates for
      mesoderm-inducing signals, with activin a particularly strong candidate. However,
      it has not been possible to inhibit mesoderm formation in vivo by specifically
      blocking activin action. Follistatin is able to inhibit the action of activin but
      not that of the mature region of Vg1, a member of the transforming growth factor
      beta family. Follistatin therefore provides a useful tool for distinguishing
      between signalling by these two factors. We have overexpressed Xenopus
      follistatin mRNA and analysed the expression of several mesodermal markers. Our
      results show an inhibition of mesodermal formation by follistatin in a
      concentration-dependent manner, showing the requirement of activin for mesodermal
      induction.

PMID- 9601990
TI  - Analysis of Peg1/Mest imprinting in the mouse.
AB  - In the mouse, Peg1/Mest is widely expressed in mesoderm-derived tissues. In
      separate studies, it has been shown to be maternally imprinted, that is, only the
      paternally inherited allele is active in mice and in humans. Here, we provide
      evidence that Peg1/Mest is expressed at very low levels in all tissues of adult
      mice as assessed by RT-PCR. Moreover, by using species-specific polymorphisms in
      the Peg1/Mest sequence we can demonstrate that in adult mice the gene remains
      imprinted in all of these tissues.

PMID- 9601991
TI  - Expression of an ascidian gene in the tip of the tail of tail-bud-stage embryos.
AB  - The occurrence of tadpole-type larvae is one of the key events used to understand
      the origin and evolution of chordates, and the tail bud of chordate embryos is
      thought to be associated with formation of the tip of the tail. Although some
      transcriptional factor genes including Brachyury are expressed in the tail bud,
      no structural genes have been reported to be expressed there. We report here that
      an ascidian gene HrTT-1 is expressed exclusively in the tip of elongating tail of
      the tail-bud embryo. This gene encodes a possible secreted protein of 415 amino
      acids with the SCP/TPX family consensus sequences.

PMID- 9601992
TI  - Demarcation of ventral territories by the homeobox gene NKX2.1 during early chick
      development.
AB  - Members of the NK-2 homeobox gene family are expressed in distinct parts of the
      central nervous system and in other non-neural territories not only in the
      fruitfly Drosophila melanogaster, but also in vertebrates. The murine Nkx2.1 (TTF
      1, T/ebp) gene was previously shown to be active and indispensable in the
      developing forebrain, hypophysis, thyroid and lung. Here we report the early
      transcript distribution of the chick NKX2.1 gene. By whole-mount in situ
      hybridization we detect a novel transient expression domain in the early
      epiblast. Further expression occurs in the ventral medial endoderm, which becomes
      restricted to the anlage fields of the thyroid and lung, in the ventral
      diencephalon and telencephalon. These findings suggest that NKX2.1 is part of a
      Nkx code which specifies ventral territories in the vertebrate embryo.

PMID- 9601993
TI  - Cloning and expression of az2, a putative zinc finger transcription factor from
      Drosophila melanogaster.
AB  - A Drosophila gene (az2), mapping to a cluster of embryonic lethals at 43BC on the
      polytene chromosomes, has been sequenced and found to encode a predicted protein
      with six consecutive C2H2 zinc finger domains. The carboxy-terminus of az2 is
      related to a number of Drosophila and mammalian transcription factors. The 5' end
      of the gene is unrelated to genes in the databases. The gene is expressed in the
      adult female, in both the carcass and ovary, but is most abundant in the ovary.
      It is expressed in the nurse cells and transported to the oocyte.

PMID- 9601994
TI  - An ergonomic comparison of in-line vs pistol-grip handle configuration in a
      laparoscopic grasper.
AB  - BACKGROUND: Laparoscopic instruments incorporate both in-line and pistol-grip
      handle configurations, yet it is unclear which design is most advantageous for
      surgeons, particularly when operating at angles perpendicular to the surgeon's
      position. We present a detailed electromyographic (EMG) comparison of these
      handle configurations under different force and angle conditions. METHODS: Nine
      general surgeons used a Microsurge grasper with the handle in an in-line (MS-IL)
      and pistol (MS-PS) configuration, as well as a standard hemostat (HE), to grasp
      and close two spring-loaded metal plates. The task was performed randomly by each
      subject with the three instrument configurations at two forces levels (0.7 N, 4.2
      N) and at three angles to the surgeons' body (0, 45, and 90 degrees). Surface EMG
      was measured from the flexor carpi ulnaris (FCU), flexor digitorum profundus
      (FDP), flexor digitorum superficialis (FDS), extensor carpi ulnaris (ECU),
      extensor digitorum comunis (EDC), and thenar compartment (TH). The peak root mean
      squared (RMS) EMG voltage was calculated for each instrument, force, and angle
      condition. Statistical comparison was carried out by ANOVA. RESULTS: Both
      laparoscopic handle configurations required significantly higher contractions of
      all muscle groups compared to the hemostat at the high force level. TH was not
      affected by laparoscopic handle configuration. MS-IL required higher FCU, ECU,
      and EDC contractions at 45 degrees compared to MS-PS. However, MS-IL decreased
      the flexor compartment muscle contractions (FDP, FDS, FCU) at 90 degrees compared
      to MS-PS. CONCLUSIONS: Laparoscopic grasping requires higher forearm and thumb
      muscle contractions compared to the use of a hemostat. The in-line handle
      configuration is no better than the pistol configuration except when grasping at
      90 degrees to the surgeon, where rotation of the handle and wrist back toward the
      surgeon significantly decreases forearm flexor compartment muscle contractions.

PMID- 9601995
TI  - Influence of acute hemorrhage and pneumoperitoneum on hemodynamic and respiratory
      parameters.
AB  - BACKGROUND: We examined the questions of whether resuscitated (compensated) acute
      hemorrhage enhances the negative effects of carbopneumoperitoneum on hemodynamic
      and respiratory parameters and whether pneumoperitoneum with helium has any
      advantages under these circumstances. Our investigation focused on the influence
      of acute hemorrhage with different gases on the cardiovascular and respiratory
      system as well as on hepatic and renal blood flow in a porcine model. METHODS:
      Cardiac and hemodynamic function were monitored via implantation of catheters in
      pulmonary artery, femoral vein, and artery. Renal and hepatic blood flow were
      recorded using a transonic volume flow meter placed at the renal and hepatic
      artery and portal vein. Twelve animals were randomly assigned to one insufflation
      gas (carbon dioxide [CO2] or helium [He]). Following baseline recordings, acute
      hemorrhage (20 ml/kg) was induced by continuous bleeding over 30 min. Animals
      then received a colloidal solution (20 ml/kg 6% hydroxyethylstarch solution) over
      30 min. Pneumoperitoneum of 12 mmHg was established, and all parameters were
      measured after 30 min of adaptation. The major endpoints of the study were
      cardiac output (CO), arterial pressure (MAP), systemic vascular resistance (SVR),
      and central venous pressure (CVP), as well as blood flow in hepatic and renal
      artery and portal vein. RESULTS: While CO and hemodynamic parameter as well as
      hepatic and renal blood flow were markedly reduced after hemorrhage, they
      returned nearly to their previous levels after resuscitation. Pneumoperitoneum
      with 12 mmHg did not further depress the cardiovascular system or reduce hepatic
      and renal blood flow. Pneumoperitoneum did not alter hepatic or renal blood flow.
      Pneumoperitoneum with helium did not substantially change the reaction of the
      cardiovascular system after resuscitated hemorrhage. CONCLUSIONS: If hemorrhage
      is compensated by proper resuscitation and hypovolemia is avoided, laparoscopic
      surgery with pneumoperitoneum of 12 mmHg appears to be not harmful. Using helium
      as the insufflating gas had no clear advantage over the carbon dioxide model.

PMID- 9601996
TI  - Is laparoscopic pyloromyotomy superior to open surgery?
AB  - BACKGROUND: We set out to determine whether laparoscopic pyloromyotomy (LPM) is
      superior to open pyloromyotomy (OPM) in babies with hypertrophic pyloric stenosis
      (HPS). METHODS: We performed a retrospective study of 36 LPM and 36 OPM. Both
      groups were comparable in terms of sex, age and weight on admission, and blood pH
      on admission and prior to surgery. In the LPM group, three trocars were used; in
      the OPM group, a small right upper quadrant transverse muscle-cutting laparotomy
      was carried out. RESULTS: LPM produces a better cosmetic result, seems to produce
      less postoperative discomfort, and results in the absence of conversion in a
      shorter hospital stay. However, the duration of the operation was significantly
      longer (32 versus 18 min). Moreover, LPM clearly entailed more complications
      (three mucosal perforations against two, and two reoperations against none in the
      open group). CONCLUSIONS: The actual series does not favor the laparoscopic
      approach over the open one, in view of the relatively high complication rate.
      Babies who are operated laparoscopically, however, seem to have less
      postoperative discomfort, a shorter hospital stay, and a better cosmetic result.
      As we are confident that the complication rate and duration of the operation will
      drop with further experience, we will continue to do LPM. LPM is not easy and
      should only be carried out when substantial experience has been gained in the
      field of pediatric laparoscopic surgery.

PMID- 9601997
TI  - Endothoracic sonography with color Doppler availability during video assisted
      thoracic surgery (videothoracoscopic operative staging with ultrasound color
      Doppler) for lung cancer staging.
AB  - BACKGROUND: The preoperative staging of lung cancer can be problematical when we
      attempt to evaluate T factor (T2-T3 versus T4) and N factor (N0 versus N1-N2). In
      some cases, radiology tests (CT scan, magnetic resonance imaging) cannot entirely
      dispel the possibility that the mediastinal structures have been infiltrated. N
      factor is evaluated mainly by dimensional criteria. However, mediastinoscopy and
      mediastinotomy do not allow the full exploration of all mediastinal mode
      stations. METHOD: Starting in 1995, we submitted 10 consecutive patients to
      videothoracoscopic operative staging with ultrasound color Doppler (VOS-USCD). In
      five cases, preoperative staging showed possible infiltration of the pulmonary
      artery (T4). In nine cases, we found involvement of the mediastinal nodes, seven
      patients were N2, and two were N3. Videothoracoscopy was performed under general
      anesthesia using a double-lumen endotracheal tube. The videothoracoscope and
      sonographic probe were inserted via three thoracoports placed in the axillary
      triangle. RESULTS: Following the results of VOS-USCD, the staging and
      subsequently the therapeutic program were modified in seven of 10 cases (70%).
      CONCLUSIONS: Our preliminary experience indicates that VOS-USCD should be applied
      to the diagnosis of patients in stage IIIA (N2) and that it is particularly
      valuable for patients in stage IIIB.

PMID- 9601998
TI  - Surgical closure of atrial septal defect. Minimally invasive cardiac surgery or
      median sternotomy?
AB  - BACKGROUND: Closure of ostium secundum atrial septal defect (ASD) vis median
      sternotomy (MS) is a simple procedure for most cardiac surgeons. Minimally
      invasive cardiac surgery (MICS) has recently been applied in the management of
      intracardiac lesions. METHODS: We report our experience in surgical closure of
      isolated ASD via MICS in 60 patients and via MS in 58 patients. There was no
      difference between these two groups in gender, age, body weight, ratio of
      systemic to pulmonary blood flow, and pulmonary arterial pressure. RESULTS: The
      duration of cardiopulmonary bypass was significantly longer in the MICS group
      than in the MS group [27 to 126 min (42 +/- 12) and 14 to 158 min (27 +/- 11),
      respectively; (p < 0.001]. However, the length of incision, incidence of
      temporary pacemaker wire insertion rate, duration of endotracheal intubation,
      timing of oral intake, postoperative day drainage amount, incidence of parenteral
      analgesic injection, postoperative length of stay, and return to normal activity
      interval were significant shorter and lower in patients of the MICS group than in
      those of the MS group. All the patients recovered rapidly from the surgery.
      Follow-up was complete in all patients, with no late complications and no
      residual shunt. CONCLUSION: Our results suggest that MICS is a good option for
      surgical closure of ASD.

PMID- 9601999
TI  - Laparoscopic cholecystectomy. Risk of missed pathology of other organs.
AB  - BACKGROUND: The wide acceptance of laparoscopic cholecystectomy (LC) has resulted
      in increased rates of cholecystectomy. However, the increased rate of LC bears
      the possibility of concomitantly missing other intra-abdominal pathologic states
      that exist concurrently with this procedure. The purpose of this report was to
      evaluate data on LC with regard to missed pathologies of other organs in a
      clinical prospective follow-up. METHODS: The clinical prospective follow-up of
      676 patients treated laparoscopically for gallstone disease at our unit since
      January 1993, was studied. Converted procedures were excluded from the follow-up
      study. RESULTS: Among 676 patients who underwent LC, 4 patients (0.6%) required
      readmission for missed pathology of another organ. The diagnostic delay ranged
      from 2 weeks to 7 months. The readmissions were due to colonic cancer (2 cases),
      carcinoma of the stomach (1 case), and fibrosis of the mesenterium of small bowel
      causing ileus (1 case), which are demonstrated in detail. According to
      retrospective analysis of the symptoms, none of the patients had typical biliary
      pain at the time of laparoscopic procedure. CONCLUSIONS: The demand for LC from
      patients and practitioners is becoming increasingly more frequent, as all become
      aware of its benefits. However, on the basis of data from the literature and this
      study, the authors would like to emphasize the need for careful history-taking,
      thorough investigation, and comparison with gallstone symptoms before LC is
      performed. It is emphasized, however, that surgeons using laparoscopic approaches
      should learn techniques of full diagnostic laparoscopy, which should be performed
      at the beginning of every procedure.

PMID- 9602000
TI  - Traumatic handling of the tumor independent of pneumoperitoneum increases port
      site implantation rate of colon cancer in a murine model.
AB  - BACKGROUND: Reports of port site tumor recurrences after laparoscopic-assisted
      resection of colon tumors have raised concerns about the safety of laparoscopic
      cancer surgery. Tumor cell suspension studies in animals have implicated the CO2
      pneumoperitoneum (pneumo) in the etiology of port tumors. Unfortunately, in
      several ways, the cell suspension model is unrealistic and does not permit
      assessment of how tumor cells become liberated from the primary tumor. The
      purpose of this study was to establish a more realistic splenic tumor model and
      to determine the relative importance of the CO2 pneumo and excessive surgical
      manipulation in the development of port site and incisional tumor recurrences.
      METHODS: Splenic tumors were established in female Balb/C mice (n = 134) via a
      subcapsular injection of 10(5) C-26 colon adenocarcinoma cells (0.1 ml volume)
      via a left-flank incision at the initial procedure. Ten days later, the animals
      were reexplored via a 1-cm left subcostal incision. Those with isolated splenic
      tumors (95%) were randomized into one of four groups: (a) control, (b) CO2
      pneumo, (c) crushed tumor, or (d) crushed tumor with pneumo. Ports were placed in
      the left lower, right lower, and right upper quadrants of each mouse. In groups 1
      and 2, the mice underwent a meticulously performed splenectomy; in groups 3 and
      4, the tumor capsule was crushed intraabdominally prior to splenectomy. In groups
      1 and 3, the subcostal incision was closed and the ports were removed after 15
      min of anesthesia. Following splenectomy, group 2 and group 4 mice underwent
      closure of the subcostal incision and a 15-min CO2 pneumo (4-6 mm Hg) after which
      the ports were removed. Twelve days later, the mice were killed and examined for
      abdominal wall tumor implants. RESULTS: Significantly more animals in group 3
      (crushed tumor) developed port site and incisional tumors than those in group 1
      (control) (p < 0.002 for both comparisons). The same results were found when
      group 4 (crush plus pneumo) was compared to group 2 (pneumo) (p < 0.002 for both
      comparisons). Regarding the port wounds, when the ports are considered
      individually (number of ports with tumors/total number of ports for each group),
      there were significantly more port tumors in the two crush groups than in the
      noncrush groups. No significant differences were noted when the port site and
      incisional tumor rates for group 1 (control) and group 2 (pneumo) were compared
      or when the results for group 2 (crush) and group 4 (crush pneumo) were compared.
      CONCLUSIONS: A splenic tumor model was successfully established. When compared to
      meticulous technique, purposefully traumatic handling of the splenic tumor before
      resection resulted in significantly more port wound and incisional tumors. In
      contrast, the addition of a pneumo after splenectomy did not significantly
      influence the incidence of port tumors in either the "good" or the "poor"
      technique groups. These results suggest that surgical technique plays a larger
      role in the development of port site tumors than the CO2 pneumoperitoneum.

PMID- 9602001
TI  - Benefit of prophylactic endoscopic sclerotherapy of esophageal varices. A
      retrospective analysis.
AB  - BACKGROUND: The therapeutic schedule in bleeding esophageal varices is today
      established: emergency endoscopy with sclerotherapy or ligation combined with
      somatostatin and decreasing portal pressure drug followed by repetitive
      sclerotherapy or ligation. But the approach to varices that do not bleed is not
      clear. METHODS: The authors submit the results of a 6-year sclerotherapeutic
      program. Since January 1989 they have treated 421 patients with varices and have
      together performed 4,115 endoscopic sclerotherapeutic procedures. Among the 421
      patients 95 were treated during acute bleeding and 254 were treated after first
      bleeding; in 72 patients prophylactic sclerotherapy (PSG) was performed. RESULTS:
      The procedure was indicated, when grade III or IV varices or high-risk signs
      and/or hepatic venous pressure gradient (HVPG) > 15 in grade II varices were
      observed. Prophylactic therapy (not-treated group-NTG) refused next 31 selected
      patients. The mean follow-up time was 32 months in the PS group and 28 months in
      NTG (n.s.). Fifteen PSG patients died (21%), while the mortality among the NTG
      patients (13 = 42% patients) was significantly higher (P < 0.02). CONCLUSIONS: We
      recommend prophylactic sclerotherapy with 1% polidocanol in patients with
      advanced varices in liver cirrhosis of varied etiology. We emphasize the need to
      perform these procedures in a department with adequate experience, where at least
      100-200 sclerotherapies per year are performed.

PMID- 9602002
TI  - How useful is colonoscopy in locating colorectal lesions?
AB  - BACKGROUND: It is important to establish the precise location of a colorectal
      lesion preoperatively. We used a model based on colorectal cancer to assess the
      efficacy of colonoscopy in locating these lesions. METHODS: We retrospectively
      analyzed all consecutive new colorectal cancer cases at the Department of
      Surgery, United Christian Hospital, Hong Kong, in 1995. RESULTS: Of the 123 cases
      reviewed by us, 84 cases satisfied the analysis criteria. The overall accuracy
      was 81%. It was especially high in the rectosigmoid region (93%) and descending
      colon (100%). The overall predictive power was 83%. It was especially high in the
      right-sided colon (100%) and the rectosigmoid region (93%). CONCLUSIONS: We
      conclude that colonoscopy is an accurate means for locating lesions in the upper
      rectum and sigmoid colon. It is also very predictive of lesions in the upper
      rectum, sigmoid colon, and right-sided colon.

PMID- 9602003
TI  - Thoracoscopic techniques for the management of intrathoracic metastases. Results.
AB  - BACKGROUND: The authors reviewed a series of 74 patients with cancer metastatic
      to the chest cavity undergoing thoracoscopic procedures. Indications,
      feasibility, and outcome of thoracoscopy were analyzed. METHODS: Perioperative
      and survival data on patients undergoing 89 operative thoracoscopic procedures
      between January 1991 and August 1993 were retrieved from a prospective database.
      These procedures included pulmonary wedge resection (n = 61), lobectomy (n = 2),
      pleurodesis (n = 11), pleural biopsy (n = 7), decortication (n = 1), and
      mediastinal mass resection (n = 2). In 13 cases, combined procedures were
      performed. Five thoracoscopies were converted to open thoracotomies to facilitate
      resection. RESULTS: Thoracoscopic pulmonary resections were performed for either
      diagnostic (n = 45) or curative (n = 18) intent. Diagnostic thoracoscopies were
      done for lesions in which less invasive biopsy attempts had failed to provide
      tissue, or that were considered too small for successful percutaneous biopsy.
      Thoracoscopic diagnostic accuracy was 100%. For the 18 patients undergoing
      potentially curative resection, mean follow-up is 15.4 months. Sixteen of these
      patients are currently alive, and eight are free of disease. Five complications
      related to the procedure included persistent air leak (n = 2), atrial
      fibrillation (n = 2), and urinary retention (n = 1). Overall hospital stay for
      thoracoscopic lung resection was 4.6 +/- 2.2 days, for converted open thoracotomy
      6.8 +/- 1.9 days, and for patients undergoing pleurodesis 8.9 +/- 5.3 days. Mean
      chest tube duration after thoracoscopic resection was 2.6 +/- 1.6 days.
      CONCLUSIONS: Thoracoscopic procedures are safe, well tolerated, and useful for
      diagnosis and treatment of selected patients with suitable intrathoracic
      metastatic disease.

PMID- 9602004
TI  - Laparoscopic vs open inguinal hernia repair. A randomized, controlled trial.
AB  - BACKGROUND: The role of laparoscopic inguinal hernia repair is controversial. The
      aim of this study was to find out whether it is justified to switch from the
      predominantly modified Bassini repair which the authors had been using to
      laparoscopic repair. METHODS: Randomized controlled trial in 120 eligible
      patients admitted for elective hernia repair in a university hospital. RESULTS:
      Sixty patients underwent laparoscopic transabdominal preperitoneal mesh repair;
      the other 60 patients had an open repair, mostly with the modified Bassini
      technique. Operative time for laparoscopic repair was significantly longer, mean
      (s.d.) 95 (28) min vs 67 (27) min (p < 0.001). The mean analogue pain score
      during the first 24 h after surgery was 36.2 (20.2) in the laparoscopic group and
      49.3 (24.9) in the open group (p = 0.006). The requirement for narcotic
      injections and postoperative disability in walking 10 m and getting out of bed
      were also significantly less following laparoscopic repair. The postoperative
      hospital stay was not significantly different, mean 2.6 (1.2) days for
      laparoscopic repair and 3.0 (1.5) days for open repair (p = 0.1). Patients were
      able to perform light activities without pain or discomfort sooner after
      laparoscopic repair, median interquartile range 8 (5-14) days vs 14 (8-19) days
      (p = 0.013). Patients also resumed heavy activities sooner, but not
      significantly, after laparoscopic repair, median 28 (17-60) days vs 35 (20-56)
      days (p = 0.25). The return to work was not significantly different, median 14 (8
      25) days after laparoscopic repair and 15 (11-21) days after open repair (p =
      0.14). After a mean follow-up of 32 months one patient developed a recurrent
      hernia 3 months after a laparoscopic repair. Laparoscopic repair was more costly
      than open repair by approximately $400. CONCLUSIONS: Laparoscopic inguinal hernia
      repair was associated with less early postoperative pain and disability and
      earlier return to full activities than open repair, but there were no benefits
      regarding postoperative hospital stay and return to work; laparoscopic repair was
      also more costly.

PMID- 9602005
TI  - A population-based survey of biliary surgery in Norway. Relationship between
      patient volume and quality of surgical treatment.
AB  - BACKGROUND: A registry was initiated in order to establish national standards for
      the quality of surgical treatment of gallstones, and to provide feedback to all
      hospitals about serious complications, in order to reduce their future incidence.
      METHODS: Prospective registration of complications was performed at all hospitals
      and collected in the National Norwegian Cholecystectomy Registry (NNCR) over a
      period of 33 months. RESULTS: Open cholecystectomy (OC) was performed in 1011
      patients, and laparoscopic cholecystectomy (LC) in 4332 patients. These figures
      represent 68% of all procedures performed nationally. The frequency of bile duct
      (BD) injury was 0. 8% for LC versus 0.7% for OC (ns); mortality was 0.1% versus
      2.1%, respectively (p < 0.05). The frequency of BD injury and mortality were
      added; the sum comprised the Severe Complication Index (SCI). A linear
      relationship was found between SCI and patient volume (correlation coefficient,
      r22 = 0.78). CONCLUSIONS: SCI was found to be the best indicator of surgical
      success. We have proposed its use as a parameter for a future prospective quality
      assurance program, along with patient volume.

PMID- 9602006
TI  - Diagnosis and treatment of common bile duct stones (CBDS). Results of a consensus
      development conference.
AB  - BACKGROUND: Common bile duct stones (CBDS) are a frequent problem (10-15%) in
      patients with symptomatic cholecystolithiasis. Over the last decade, new
      diagnostic and surgical techniques have expanded the options for their
      management. This report of the Consensus Development Conference is intended to
      summarize the current state of the art, including principal guidelines and an
      extensive review of the literature. METHODS: An international panel of 12 experts
      met under the auspices of the European Association of Endoscopic Surgery (EAES)
      to investigate the diagnostic and therapeutic alternatives for gallstone disease.
      Prior to the conference, all the experts were asked to submit their arguments in
      the form of published results. All papers received were weighted according to
      their scientific quality and relevance. The preconsensus document compiled out of
      this correspondence was altered following a discussion of the external evidence
      made available by the panel members and presented at the public conference
      session. The personal experiences of the participants and other aspects of
      individualized therapy were also considered. RESULTS: Our panel of experts agreed
      that the presence of common bile duct stones should be investigated in all
      patients with symptomatic cholecystolithiasis. Based on preoperative noninvasive
      diagnostics, either endoscopic retrograde cholangiopancreaticography (ERCP) or
      intraoperative cholangiography should be employed for detecting CBDS. Eight of
      the 12 panelists recommended treating any diagnosed CBDS. For patients with no
      other extenuating circumstances, several treatment options exist. Stones can be
      extracted during ERCP, or either before or (in exceptional cases) after
      laparoscopic or open surgery. Bile duct clearance should always be combined with
      cholecystectomy. Evidence for further special aspects of CBDS treatment is
      equivocal and drawn from nonrandomized trials only. CONCLUSIONS: The management
      of common bile duct stones is currently undergoing some major changes. Many
      diagnostic and therapeutic strategies need further study.

PMID- 9602007
TI  - Laparoscopic cholecystectomy after pancreatic debridement.
AB  - BACKGROUND: Pancreatic debridement is a lifesaving operation in patients with
      severe acute pancreatitis and pancreatic or peripancreatic necrosis. Even in the
      presence of gallstones, cholecystectomy may be avoided during the procedure, but
      definitive treatment of the stones is needed at a later stage. METHODS: Five
      patients (median age 58 years) underwent laparoscopic cholecystectomy, at a
      median time interval of 15 months, after pancreatic debridement via a dome-shaped
      upper abdominal incision for severe acute pancreatitis. The use of alternative
      methods for primary access, additional cannulae to enable division of adhesions,
      the harmonic scalpel, and the fundus first technique made the laparoscopic
      approach possible and safe. RESULTS: The median operating time was 130 min. Four
      patients were discharged home the first or second postoperative day. One patient
      required a "mini-laparotomy" for drainage of a periumbilical hematoma and was
      discharged on the 13th day. CONCLUSIONS: Laparoscopic cholecystectomy can be
      considered an effective and safe approach for the treatment of gallstones in
      patients who have undergone pancreatic debridement.

PMID- 9602008
TI  - Pancreatic carcinoma. Diagnostic and prognostic implications of a normal
      pancreatogram.
AB  - BACKGROUND: The aim of this study was to establish the implications of a normal
      pancreatogram in patients with pancreatic cancer. METHODS: We reviewed all ERCP
      done at our institution for the period 1983-92 and studied 62 of 727 patients who
      had a diagnosis of pancreatic (n = 416) or biliary (n = 311) cancer but a normal
      pancreatic duct. RESULTS: Thirty of the 62 patients had pancreatic cancer. In 15
      cases, the ERCP diagnosis was incorrect, and in 19 cases, Santorini's duct was
      not visualized. Other imaging revealed a pancreatic head mass in 25 patients (2.5
      >7 cm). Only three patients had resectable tumors; another eight underwent
      laparotomy. Five had bypass surgery, 10 required biliary stenting, and nine had
      no treatment. Four patients died in hospital, and eight were lost to follow-up.
      In the remaining 18 patients, median survival was 7 months (range, 1-30 months).
      CONCLUSION: A normal pancreatogram does not exclude the diagnosis of pancreatic
      cancer, nor does it confer a better prognosis.

PMID- 9602009
TI  - Splenic artery embolization before laparoscopic splenectomy. An update.
AB  - BACKGROUND: This study assessed preoperative splenic artery embolization before
      laparoscopic splenectomy. METHODS: Preoperative splenic artery embolization was
      used in 26 of 54 patients (48%) undergoing laparoscopic splenectomy. Between 1992
      and 1994, this procedure was used in all patients with spleens shorter than 20 cm
      (group I), except the first two (18/20). An anterior surgical approach was used.
      After 1994 (group II), embolization was not used for these patients (0/26), and a
      lateral surgical approach was used. Throughout the study period, all patients
      with spleens longer than 20 cm had embolization (8/8). RESULTS: Five
      complications occurred, three related to the use of small-particle embolic
      material (microspheres, gelatin foam powder). In group I, the conversion rate was
      lower than that of most current series, largely because of embolization. In group
      II, similar results were obtained because of experience and a better surgical
      approach (i.e., lateral). CONCLUSIONS: Preoperative splenic artery embolization
      is not necessary for spleens shorter than 20 cm. Increased experience and mostly
      the lateral surgical approach have permitted a shorter operation and a low
      conversion rate (4%) similar to the rate achieved with embolization and the
      anterior approach in the initial stages of the study. Embolization is used for 20
      to 30-cm spleens. The conversion rate is higher (17%), and blood replacement is
      required frequently (83%). Despite embolization, laparoscopic splenectomy for
      spleens longer than 30 cm is futile at this time (100% conversion).

PMID- 9602010
TI  - High-burst-strength, feedback-controlled bipolar vessel sealing.
AB  - BACKGROUND: The inherent tedium of intracorporeal knot tying has stimulated
      greater interest in energy-based and mechanical alternatives for hemostasis.
      METHODS: Three hundred thirty-one arteries and veins were sealed by application
      of precisely controlled electrothermal energy and physical pressure, allowing for
      brief cooling in compression, in experimental animals and fresh abattoir vessels.
      These seals were compared for bursting strength with occlusions by ultrasonic and
      bipolar coagulation, surgical clips, and ligatures. RESULTS: Ultrasonic and
      bipolar occlusions were significantly less likely to have burst strengths greater
      than 400 mmHg as compared with seals, clips, and ligatures (p < 0.001). Seal
      competence could be visually assessed by its translucence. CONCLUSIONS: Precise
      energy control with physical compression, including a brief cooldown, produces a
      distinctive, translucent seal of partially denatured protein that can typically
      be transected after a single application. These seals have bursting strengths
      comparable to those of clips and ligatures and resist dislodgement because they
      are intrinsic to the vessel wall structure.

PMID- 9602011
TI  - Misleading symptoms after a minor blunt chest trauma. Thoracoscopic treatment of
      diaphragmatic rupture.
AB  - We present a case of missed diaphragmatic rupture which was treated
      thoracoscopically. Rupture of the diaphragm is a serious complication of blunt
      trauma. The diaphragmatic injury can easily be overlooked. This report
      illustrates the diagnostic dilemma in a patient where the injury was missed at
      the time of initial presentation. The role of thoracoscopy both for diagnosis and
      therapy is discussed.

PMID- 9602012
TI  - Laparoscopic clipping of the median sacral artery in huge sacrococcygeal
      teratomas.
AB  - Huge sacrococcygeal teratomas in the newborn can cause significant morbidity and
      even death due to cardiac failure, hemorrhage, or both. Surgical removal is the
      treatment of choice, but can indicate these events. Ligation of the median sacral
      artery, which always supplies the tumor, prior to its removal has been advocated,
      but in the past this procedure required a formal laparotomy. Nowadays, it can be
      easily accomplished laparoscopically, as this case report demonstrates.

PMID- 9602013
TI  - Two-trocar technique for terminal sigmoid colostomy in a patient with complex
      pelvic fracture.
AB  - We report a multiple trauma case with complex pelvic fractures and perineal
      wounds. The patient had a laparoscopic abdominal exploration with a simultaneous
      laparoscopic colostomy using the same wounds. Only two trocars were needed to
      perform both procedures. The technique is detailed here. The procedures were
      performed in less than an hour, with excellent postoperative recovery, achieving
      complete diversion of the rectal fecal contents.

PMID- 9602014
TI  - EndoScope: world literature reviews 

PMID- 9602015
TI  - Laparoscopic management of Tenchkoff catheters in continuous ambulatory
      peritoneal dialysis. A one-port technique.
AB  - We describe a one-port laparoscopic technique for assisting in Tenchkoff catheter
      placement and salvaging obstructed ones in patients requiring continuous
      ambulatory peritoneal dialysis (CAPD). This unique technique enables diagnostic
      laparoscopy, adhesiolysis, repositioning of catheters, and omentectomy to be
      performed without laparotomy. Six patients were treated. Only one 10-mm port was
      required, using an operating laparoscope and an instrument introduced through the
      working channel of the laparoscope. Adhesiolysis was performed under laparoscopic
      vision; omentectomy and flushing of blocked catheters were carried out
      extracorporeally. The catheters were then repositioned to the pelvic cavity under
      laparoscopic vision. All patients were followed up for 6-10 months. No mechanical
      problem was noticed. Our one-port laparoscopic technique is a simple and
      effective method for treating patients who have mechanical problems with their
      peritoneal dialysis catheters.

PMID- 9602016
TI  - Laparoscopic gastrostomy according to Janeway.
AB  - Percutaneous endoscopic gastrostomy is not suitable for all patients requiring
      gastrostomies. Patients with endoscopically impassable tumors require a safe and
      effective alternative procedure for paraesophageal alimentation. We present the
      surgical technique and results of the laparoscopic gastrostomy according to
      Janeway. Using an endoscopic stapling device a gastric tube is created from a
      stomach fold, led out through the trocar site, and fixed to the skin in the left
      upper quadrant. Via an inserted catheter enteral alimentation can be performed
      intermittently since the gastrostoma is continent. Between July 1995 and November
      1996 laparoscopic gastrostomy was performed in 15 patients (10 male, five female)
      with tumors in the pharynx or esophagus. Mean operation time was 35 min. One
      stoma necrosis developed; the other postoperative courses were complication-free.
      All gastrostomies were continent. Laparoscopic gastrostomy is easy to perform and
      involves minimal discomfort and complications for the patient.

PMID- 9602018
TI  - News and notices 

PMID- 9602017
TI  - Posterolateral approach. An alternative strategy in laparoscopic splenectomy.
AB  - Laparoscopic splenectomy (LS) is effective and technically feasible for treating
      various hematological diseases, especially idiopathic thrombocytopenic purpura
      (ITP). An anterior approach to the vascular pedicle is usually described.
      However, in this approach to the splenic hilum, the dissection of the splenic
      artery is often difficult. A total of 13 patients with ITP underwent elective
      laparoscopic splenectomy. We utilized a laparoscopic posterolateral approach
      involving dissection of the suspensory ligaments at the lower pole, then
      dissection and division of the posterolateral attachments, followed by the
      dissection and ligation of all splenic branches near the splenic parenchyma. This
      procedure was completed in 11 of our 13 patients and converted to open surgery in
      the other two patients. Mean operative time was 3 h; mean postoperative stay was
      3 days. No blood transfusion was required, and no complications were noted in the
      postoperative period. The posterolateral approach provides better visualization
      and control of branches of the splenic vein and artery in the splenic hilum. It
      also permits visualization and control of surgical hemorrhage through the
      operating ports.

PMID- 9602019
TI  - Structural and functional analysis of the 5'-transcription control region for the
      human alpha2-HS glycoprotein gene.
AB  - The human alpha2-HS glycoprotein (A2HS) and rat phosphoprotein of Mr 63000 (pp63)
      are homologous plasma proteins and members of the fetuin superfamily. A2HS is
      involved in important functions such as inhibition of the tyrosine kinase
      activity of the insulin receptor, regulation of calcium metabolism and
      osteogenesis as well as protease inhibitory activity. We report an analysis of
      the 5' transcription control region (4 kb) of the A2HS gene. Its most proximal
      300 nt display a very potent transcriptional activity. The latter is likely
      accounted for by C/EBP and NF1 binding sites that are conserved from the human
      A2HS gene to the rat pp63 gene. In contrast, these human and rat genes appear to
      largely diverge beyond their proximal promoter.

PMID- 9602020
TI  - Involvement of medial septal glutamate and GABAA receptors in behaviour-induced
      acetylcholine release in the hippocampus: a dual probe microdialysis study.
AB  - In the present study, the role of medial septal receptors in behaviour-induced
      increase in acetylcholine (ACh) release in hippocampus was investigated using
      dual-probe microdialysis in combination with a simple behavioural procedure.
      gamma-Aminobutyric acid (GABA) and glutamate receptor agonists and antagonists
      were administered by retrograde dialysis into the medial septal area, while ACh
      was measured in the ventral hippocampus. Rats were behaviourally activated by
      immobilization or handling, but only handling was performed during drug
      treatment. The GABAA receptor agonist muscimol did not affect ACh release, but
      blocked the handling-induced increase in ACh release completely. In addition,
      muscimol administration induced behavioural activity. Administration of the GABAA
      receptor antagonist bicuculline increased ACh release more than 2-fold. However,
      handling-induced increase in ACh release, expressed as percentage of drug-induced
      release, was similar to that of controls. Administration of the glutamate
      receptor agonists N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) in the septal area increased hippocampal
      ACh levels, but reduced the handling-induced increase in ACh release. The NMDA
      antagonist, 3-((R)-2-carboxypiperazin-4-yl) (CPP) increased ACh levels
      moderately, and reduced handling-induced increase in ACh release. However,
      similarly to muscimol, CPP administration induced behavioural activity. The
      AMPA/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) did not
      affect behaviour or basal ACh levels, but attenuated the handling-evoked ACh
      release. We conclude that the handling-induced increase in hippocampal ACh levels
      is mediated via stimulation of septal non-NMDA, and possibly NMDA receptors,
      whereas GABAA receptors are probably not involved. The feasibility of the
      experimental design is further discussed.

PMID- 9602021
TI  - Isolation and sequence analysis of metalloprotease gene from Vibrio mimicus.
AB  - The vmc gene encoding a metalloprotease of Vibrio mimicus (ATCC 33653) was cloned
      in Escherichia coli and sequenced. The vmc gene contained 1884 nt sequence which
      codes a polypeptide of 628 amino acids with a predicted molecular mass of 71,275
      Da. The deduced amino acid sequence had the similarity of 68.5% with V.
      parahaemolyticus metalloprotease. The consensus sequence of a zinc binding motif
      (HEXXH) was identified to be HEYTH. The zymography analysis showed a
      gelatinolytic protein band around molecular mass of 61 kDa, and this result
      suggested that the cloned metalloprotease may undergo processing during
      secretion.

PMID- 9602022
TI  - The expressions of epidermal growth factor receptor mRNA and protein gene product
      9.5 in developing rat brain.
AB  - To clarify the role of epidermal growth factor receptor (EGFR) in brain
      development, especially with regard to neuron differentiation, EGFR mRNA
      expression was studied by in situ hybridization in embryonic day (E)12, E16,
      postnatal day (P)1, P4, P15, P29 and adult rat, using protein gene product (PGP)
      9.5 as a neuron marker. The primary germinal zone (neuroepithelium) expressed
      neither PGP 9.5 immunoreactivity (IR) nor EGFR mRNA. In the developing brain,
      cells expressing EGFR mRNA but not PGP 9.5 IR were found in the secondary
      germinal zone such as the subventricular zone and cerebellar external germinal
      layer, the cortical plate and, in later stage animals, the fiber tracts. Cells
      expressing both EGFR mRNA and PGP 9.5 IR appeared in a differentiating field. In
      the adult brain, strong EGFR mRNA expression was observed in Purkinje cells,
      Golgi cells, some hippocampal cells and neurons of the diencephalon, pontine and
      medullary nuclei, and weak expression was seen in neurons of the cerebral cortex.
      These results suggest that EGFR is related to the process of differentiation and
      maturation of neurons and the maintenance of some types of adult neurons.

PMID- 9602024
TI  - Distribution of the 5-HT5A serotonin receptor mRNA in the human brain.
AB  - The 5-HT5A receptor is a member of a new subfamily of serotonin [5
      hydroxytryptamine (5-HT)] receptors recently cloned from the human and rodent
      brain. The role of this receptor in normal brain functions as well as its
      possible involvement in pathological states is still to be determined. We
      therefore studied the regional distribution and cellular localization of 5-HT5A
      receptor mRNA in human brain sections from autopsy samples by in situ
      hybridization histochemistry, in order to obtain anatomical information which
      might be useful in formulating hypotheses on possible functions subserved by this
      receptor in the central nervous system (CNS). Our results showed that the main
      sites of 5-HT5A mRNA expression were the cerebral cortex, hippocampus and
      cerebellum. In the neocortical regions, the 5-HT5A receptor mRNA was mainly
      distributed in the layers II-III and V-VI. In the hippocampus, the dentate gyrus
      and the pyramidal cell layer of the CA1 and CA3 fields expressed 5-HT5A mRNA at
      high levels. The broad distribution in the neocortex and hippocampus supports the
      view that the 5-HT5A receptor in these areas might be implicated in high cortical
      and limbic functions. The 5-HT5A mRNA was widely distributed in the cerebellum
      where it was highly expressed in the Purkinje cells, in the dentate nucleus and,
      at a lower level, in the granule cells. Since the cerebellum receives diffuse
      serotonergic afferents, this finding suggests that the 5-HT5A receptor may have
      an important role in mediating the effects of 5-HT on cerebellar functions.

PMID- 9602025
TI  - Stability of the C-terminal peptide of CETP mediated through an (i, i + 4) array.
AB  - Based on circular dichroism (CD), we have found an essential (i, i + 4) alpha
      helix stabilizing array in the C-terminus region for the cholesteryl ester
      transfer protein (CETP) between histidine 466 and aspartic acid 470. This region
      apparently corresponds to an amphipathic alpha-helix. The behavior of this
      peptide in solution in comparison with a mutant peptide (D470N) was also analyzed
      by dynamic light scattering (DLS). The results showed that alpha-helix
      stabilization is not due to peptide aggregation. The thermodynamic estimation of
      stability supports the idea that the phenomenon is carried out through an (i, i +
      4) array. The representation of the C-terminal region as an amphipathic alpha
      helical peptide shows that lipid-binding activity might be in part due to both
      the asymmetric polar/non-polar residue distribution and to the presence of an (i,
      i + 4) array important for helix stability.

PMID- 9602026
TI  - Genomic structure of Unp, a murine gene encoding a ubiquitin-specific protease.
AB  - The murine Unp gene encodes a ubiquitin-specific protease, a member of a family
      of enzymes that includes the product of the human tre-2 oncogene. The Unp gene
      has previously been mapped to chromosome 9. We have cloned in bacteriophage a 50
      kilobase region of chromosome 9 containing the Unp gene, and have determined the
      nucleotide sequence of the gene. The gene has 22 exons, distributed over 47.4 kb.
      A processed ribosomal S2 pseudogene was identified in the third intron of the Unp
      gene. Expression of Unp is driven by a GC-rich, 'housekeeping' type promoter.

PMID- 9602027
TI  - Identification and characterization of RPTP rho, a novel RPTP mu/kappa-like
      receptor protein tyrosine phosphatase whose expression is restricted to the
      central nervous system.
AB  - We describe the cloning, chromosomal localization and characterization of
      RPTPrho, a new member of the RPTPmu/kappa phosphatase subfamily. Receptor
      tyrosine phosphatases in this subfamily are comprised of a MAM domain near the N
      terminal, an immunoglobulin-like domain, four fibronectin type III repeats, a
      single transmembrane domain, and a large juxtamembrane segment followed by two
      intracellular phosphatase domains. An alternatively spliced mini-exon was
      identified in the extracellular segment of RPTPrho, between the fourth
      fibronectin type III repeat and the transmembrane domain. The RPTPrho gene was
      mapped to human chromosome 20 and mouse chromosome 2. Northern blot analysis
      demonstrated that RPTPrho expression was restricted to the central nervous
      system, and in situ hybridization studies showed that the RPTPrho transcript was
      distributed throughout the murine brain and spinal cord. Exceptionally high
      levels of the transcript were present in the cortex and olfactory bulbs during
      perinatal development, but were down-regulated during postnatal week two. The
      motifs found in the extracellular segment of type II receptor protein tyrosine
      phosphatases are commonly found in neural cell adhesion molecules, suggesting
      that RPTPrho may be involved in both signal transduction and cellular adhesion in
      the central nervous system.

PMID- 9602028
TI  - Topographical distribution of [125I]-glial cell line-derived neurotrophic factor
      in unlesioned and MPTP-lesioned rhesus monkey brain following a bolus
      intraventricular injection.
AB  - The present study determined the topographical distribution profile for [125I]
      glial cell line-derived neurotrophic factor in unlesioned and MPTP-lesioned
      (unilateral intracarotid injection) rhesus monkeys following an intraventricular
      injection. Autoradiographic analysis showed that following a bolus
      intraventricular injection, there was widespread distribution of [125I]-glial
      cell line-derived neurotrophic factor throughout the ventricular system (walls of
      lateral, third, and fourth ventricles and aqueduct), with some accumulation at
      the lateral ventricle injection site, possibly associated with the ependymal cell
      layer. In both unlesioned and MPTP-lesioned monkeys, there was labelling of the
      cerebral cortex, substantia nigra/ventral tegmental area and sequestration of
      [125I]-glial cell line-derived neurotrophic factor adjacent to the hippocampal
      formation, globus pallidus, ventral to and in the substantia nigra. However,
      [125I]-glial cell line-derived neurotrophic factor did not appear to diffuse
      readily or accumulate in the caudate-putamen even though there was some
      penetration away from the ventricular walls. Throughout the brain, there was also
      substantial non-parenchymal labelling of [125I]-glial cell line-derived
      neurotrophic factor, possibly associated with extracellular matrix components,
      meninges and vasculature due to the heparin binding properties of glial cell line
      derived neurotrophic factor. In addition to the extensive loss of tyrosine
      hydroxylase immunoreactivity within the substantia nigra, there was also
      decreased accumulation of [125I]-glial cell line-derived neurotrophic factor and
      reduced glial cell line-derived neurotrophic factor immunoreactivity ipsilateral
      to the lesion. Microscopic analysis showed that glial cell line-derived
      neurotrophic factor immunoreactivity was associated with upper cortical layers
      including a high density of immunoreactivity at the surface of the cortex
      (meningeal, pial layer, vasculature) and around the ventricular walls (with some
      cellular labelling and labelling of vasculature). Moderate staining was observed
      in nigral cells contralateral to the MPTP-lesion, whereas only minimal levels of
      that glial cell line-derived neurotrophic factor immunoreactivity were detected
      ipsilateral to the lesion. This study shows that intraventricularly injected
      glial cell line-derived neurotrophic factor accumulates not only around the
      ventricular walls, but also in specific brain regions in which sub-populations of
      cells are more readily accessible than others. The presence of cells labelled
      with [125I] and immunopositive for glial cell line-derived neurotrophic factor in
      the substantia nigra indicates that these cells are a target for the trophic
      factor following intraventricular administration. Thus, the behavioral
      improvement observed in MPTP-lesioned monkeys following an intraventricular
      injection of glial cell line-derived neurotrophic factor is likely the result of
      activation of nigral cells.

PMID- 9602029
TI  - Behavioral and heart rate effects of infusing kainic acid into the dorsal
      midbrain during early development in the rat.
AB  - The dorsal midbrain including the periaqueductal gray (PAG) is involved in the
      control of threat-induced vocalizations and other behavioral and autonomic
      defensive responses in adult animals. Little is known of its function early in
      life. The present study examined the ability of kainate receptor stimulation in
      these midbrain areas to trigger behavioral and physiological responses during the
      first three postnatal weeks in the rat. Kainate (0.03-0.3 nmol) was infused into
      the dorsal midbrain of postnatal day 7 (P7), P14 and P21 rat pups. At P7,
      subjects exhibited only a brief period of locomotor activation immediately
      following infusion of kainate. There were no changes in the heart rate or in any
      other behavioral measures, including their production of ultrasonic
      vocalizations. At P14, kainate induced adult-typical escape behaviors consisting
      of running and jumping, increases in the duration of time spent immobile, and
      increases in heart rate. At P21, subjects given kainate exhibited escape behavior
      coupled with elevated heart rate and immobility coupled with decreased heart
      rate. P14 and P21 subjects produced only small, non-significant increases in
      their production of ultrasonic vocalizations. These results indicate that kainate
      receptor stimulation in the dorsal midbrain does not mediate most adult-typical,
      threat-induced responses until sometime during the second postnatal week in the
      rat.

PMID- 9602031
TI  - Electrostatic interaction between NADH-cytochrome b5 reductase and cytochrome b5
      studied by site-directed mutagenesis.
AB  - Electrostatic interaction between NADH-cytochrome b5 reductase and cytochrome b5
      was studied by site-directed mutagenesis. The target residues for mutagenesis
      were selected on the basis of the previously reported chemical cross-linking
      study of these two proteins, which implicated possible charge-pair interactions
      between Lys-41, Lys-125, Lys-162, and Lys-163 of the enzyme, and Glu-47, Glu-48,
      Glu-52, Glu-60, Asp-64 (group A), and heme propionate of cytochrome b5. Mutant
      reductases that lost one of the above-listed Lys residues showed higher K(m)
      values for cytochrome b5 and lower kcat values than those of the wild type,
      suggesting that all of the examined Lys residues participate in binding with
      cytochrome b5 as reported previously. In contrast, a removal of one of (or even
      all of) the group A residues from cytochrome b5 by mutagenesis caused no
      significant effect on the catalytic properties of cytochrome b5. Additional
      elimination of another set of negative residues (Glu-41, Glu-42, Asp-57, and Glu
      63 (Group B)), which are also located close to heme, elevated the K(m) value by
      more than five folds. These results suggest that there should be other acidic
      residue(s) than group A in cytochrome b5 which participate in binding with NADH
      cytochrome b5 reductase.

PMID- 9602032
TI  - Cloning and sequence analysis of Hsp89alpha DeltaN, a new member of theHsp90 gene
      family.
AB  - We have identified a novel member of the Hsp90 gene family. This new gene,
      Hsp89alpha DeltaN, is remarkable in that it appears to represent a recent
      evolutionary event. Hsp89alpha DeltaN is identical in nucleotide sequence to
      Hsp89alpha for codons 224 to 732 (end). However, Hsp89alpha DeltaN cDNA lacks the
      ATP/geldanamycin binding domain (codons 1-220), instead containing 544
      nucleotides of unique DNA at its 5' end including 30 novel codons.

PMID- 9602033
TI  - Effects of diverse developmental environments on neuronal morphology in domestic
      pigs (Sus scrofa).
AB  - Potential effects of environmental rearing conditions on the brains of farm
      animals have not been examined experimentally, with the exception of one report
      for pig somatosensory cortex. The goal of the present experiment was to determine
      whether different developmental environments in use in agricultural production
      units affect neuronal morphology in the pig cerebral cortex. Littermate female
      pigs (gilts) were cross-fostered at birth and reared in either an indoor (n = 6)
      or outdoor (n = 6) production unit for 8 weeks. Additional littermates (n = 6)
      were sacrificed at 3 days of age to provide a developmental reference point.
      Brains were fixed by perfusion and stained by the Golgi-Cox method. The primary
      somatosensory, auditory and visual cortices were sectioned at 170 microns, and
      layer IV stellate neurons (n = 492) were digitized and 3-dimensionally
      reconstructed. Measurements of dendritic length, membrane surface area, total
      number of segments, number of 1st- through 7th-order dendrites, spine density,
      soma area, and soma form factor were taken. In auditory cortex neurons, outdoor
      pigs compared to indoor pigs had (a) significantly more primary dendrites, (b)
      significantly greater spine density, and (c) trends of increases both in number
      of 2nd- and 3rd-order dendrites and in total dendritic length. In visual cortex
      neurons, indoor pigs had significantly more 7th-order dendrites, whereas in all
      three cortical areas, the indoor animals had more 5th-order dendrites. Multiple
      morphological differences occurred in stellate cell populations between the three
      sensory areas of the Week 8 pigs. Also, within different cortical areas,
      dendritic morphology changed substantially from 3 days to 8 weeks of age. Further
      investigations are needed to determine which environmental factors are critical
      in producing the observed changes in brain morphology and whether other brain
      effects may be produced by varying developmental environments.

PMID- 9602035
TI  - Changes in IP3R1 and SERCA2b mRNA levels in the gerbil brain after chronic
      ethanol administration and transient cerebral ischemia-reperfusion.
AB  - Despite epidemiological studies indicating a positive relationship between
      alcohol and stroke, little is known with regard to effect of chronic alcohol on
      neuronal injury after stroke. In this study, we examined the effect of chronic
      ethanol on mRNA levels of sarcoplasmic or endoplasmic Ca2+-ATPase (SERCA2b) and
      inositol 1,4, 5-triphosphate receptor (IP3R1) in gerbils subjected to global
      cerebral ischemia induced by ligation of both common carotid arteries. Gerbils
      were given daily by intragastric intubation either a liquid diet containing
      ethanol (4 g/kg) or the same diet with an isocaloric amount of sucrose for 35
      days. They were subsequently subjected to a 5 min ischemic insult followed by
      reperfusion for 48 h. In agreement with other studies, ischemic insult caused
      significant decreases (P<0.05) in mRNA levels of both IP3R1 and SERCA2b in the
      hippocampal CA1 region but not in the dentate gyrus. Nevertheless, despite a
      significant (P<0.05) decrease in SERCA2b mRNA in the Purkinje neurons, chronic
      ethanol did not alter the expression of this mRNA species in the hippocampal CA1
      neurons nor did it alter the decrease in SERCA2b mRNA due to cerebral ischemic
      insult. Since IP3R1 and SERCA2b are key mediators for regulation of intracellular
      Ca2+ stores, the decrease in SERCA2b mRNA but not IP3R1 mRNA in cerebellar
      neurons may be an important mechanism underlying alteration of calcium
      homeostasis and cerebellar degeneration upon chronic ethanol consumption.

PMID- 9602036
TI  - Structural analysis of mutant hen egg-white lysozyme preferring a minor binding
      mode.
AB  - Trp62 in hen egg-white lysozyme has general features observed in protein
      carbohydrate interactions, a stacking interaction toward nonpolar surface of the
      substrate sugar residue B and a hydrogen bonding network with the residue C. Our
      previous report (I. Kumagai, K. Maenaka, F. Sunada, S. Takeda, K. Miura, Eur. J.
      Biochem. 212 (1993) 151-156.) showed that the substitution of Trp62 changed the
      substrate binding modes; especially, the Trp62His mutant exhibited the drastic
      change of the binding mode and preferred to a minor binding mode of the wild-type
      enzyme. In order to clarify the relationship between functional and structural
      changes of the Trp62His mutant, we analyzed the structure of the Trp62His mutant
      hen lysozyme complexed with the substrate analogue, (GlcNAc)3, by X-ray
      crystallography. The overall protein structure in the mutant lysozyme complex was
      almost identical to that in the wild-type. His62 shared almost the same plane as
      the indole ring of Trp62 of the wild-type. Although the (GlcNAc)3 molecule which
      is an inhibitor against the wild-type lysozyme was cocrystallized, the Trp62His
      mutant did not put it in the sites A-B-C but hydrolyzed it as a substrate. One of
      the products, (GlcNAc)2, whose reducing end is alpha-anomer, was bound in another
      binding mode sticking out from the active-site cleft. The hydrolytic activity
      against the synthetic substrate showed that the mutant was a beta-anomer
      retaining enzyme, so the alpha-anomer product was converted from the beta-anomer
      product. Therefore, the Trp62His mutant showed the remarkable change of the
      substrate binding modes not by alteration of the catalytic system but possibly by
      subtle rearrangement of general features of protein-carbohydrate interactions
      between His62 and the sugar residues B and C.

PMID- 9602037
TI  - Evidence for involvement of the lateral parabrachial nucleus in mediation of
      cholinergic inputs to neurons in the rostral ventrolateral medulla of the rat.
AB  - We examined whether sites in the lateral parabrachial nucleus (PBN) where L
      glutamate produced increases in arterial pressure were involved in mediation of
      cholinergic inputs to neurons in the rostral ventrolateral medulla (RVLM). Male
      Wistar rats were anesthetized, paralyzed and artificially ventilated. Unilateral
      microinjection of L-glutamate into the lateral PBN produced a pressor response.
      Microinjection of the muscarinic receptor antagonist scopolamine into the
      unilateral RVLM inhibited the pressor response to L-glutamate injected
      ipsilaterally into the lateral PBN, whereas microinjection of the cholinesterase
      inhibitor physostigmine into the RVLM enhanced it. PBN microinjection of L
      glutamate also enhanced the firing rate of RVLM sympathoexcitatory neurons and
      the enhancement of the firing rate was inhibited by scopolamine iontophoretically
      applied on neurons. PBN injection of L-glutamate produced a tetrodotoxin (TTX)
      sensitive release of ACh in the RVLM. Unilateral microinjection of TTX into the
      lateral PBN inhibited the pressor response induced by RVLM microinjection of
      physostigmine. These results provide evidence that neurons in the pressor sites
      of the lateral PBN are involved in mediation of cholinergic inputs responsible
      for pressor responses in the RVLM.

PMID- 9602038
TI  - Molecular cloning and expression of an avian rab5 homolog.
AB  - A chicken rab5 cDNA was isolated that contains the complete open reading frame
      for a protein of 216 amino acids, which, by comparison with available rab5
      sequences from other species, is most closely related to the rab5c isoform. Two
      rab5 transcripts of 1.3 and 1.8 kb were detectable in various chicken tissues;
      they are abundant in tissues with high endocytic activity, such as brain, ovary,
      and testis. Similarly, high levels of rab5 protein expression were found in
      endocytotically active tissues and were increased upon estrogen treatment of
      roosters.

PMID- 9602039
TI  - Cell death and associated c-jun induction in perinatal hypoxia-ischemia. Effect
      of the neuroprotective drug dexamethasone.
AB  - Previous studies in a model of unilateral hypoxia-ischemia in the developing rat
      brain have shown induction of the mRNAs of c-fos and c-jun and presence of
      apoptotic DNA fragmentation. In this same model, dexamethasone confers
      neuroprotection if given before the insult. Since c-fos and c-jun have been
      involved in several models of cell death, we investigated whether the
      neuroprotective effect of dexamethasone could be associated with changes in
      expression of these genes. Rat pups, pre-treated with either 0.5 mg/kg
      dexamethasone or vehicle 48 h, 24 h and immediately before the injury, were
      subjected to ligation of the left common carotid artery followed by 3 h hypoxia.
      Analysis of c-fos and c-jun expression at 2 h, by means of in situ hybridization,
      revealed diminished induction in dexamethasone-treated animals. Jun
      immunoreactivity, but not Fos, and DNA fragmentation, assessed by in situ end
      labeling of fragmented DNA, were present at 24 h only in vehicle-injected
      animals. Electrophoresis of brain extracted DNA revealed a ladder pattern in all
      the animals. Our results show a relationship between Jun overexpression and cell
      death in the hypoxic-ischemic developing brain and suggest that dexamethasone
      exerts its protective effect anteceding immediate early gene induction, at some
      early point in post-ischemic signal transduction.

PMID- 9602041
TI  - 1H NMR studies of azide binding to cytochrome c.
AB  - The binding of azide ion to the heme iron of ferricytochrome c in D2O is studied
      using 1H NMR methods at pH 7.0 and 300 K or 315 K. Some hyperfine shifted
      resonances arising from heme peripheral protons and resonances of side-chain
      protons of some amino acid residues in N3-cyt c have been assigned using 2D EXSY
      and DQF-COSY methods. The majority of the heme pocket side-chain proton signals
      have been identified. The 1D nuclear overhauser effect (NOE) difference spectra
      and 2D NOESY spectrum are presented and changes in NOE patterns between the heme
      and certain residues, and several residues around the axial ligand are
      interpreted in terms of changes in the pocket structure. Interpretation of NOE
      data indicates that conformation changes are obvious on the Met80 side of the
      heme cavity in the environment of the axial ligand in N3-cyt c. In addition,
      kinetics analysis of azide binding to cyt c is studied using 2D EXSY method.

PMID- 9602042
TI  - Identification of mouse itih-4 encoding a glycoprotein with two EF-hand motifs
      from early embryonic liver.
AB  - An essential feature of cell differentiation is the specificity of signal
      transduction events from extracellular cues, which are considered to be conferred
      by scaffold, anchoring and adaptor proteins. Our aim was to identify important
      scaffolding proteins required for liver development. Utilizing subtraction
      hybridization of embryonic liver cDNA libraries, here we report the full length
      cDNA sequence for mouse itih-4 (Inter-alpha-trypsin inhibitor H4). Itih-4 encodes
      a 942 amino acid protein containing two EF-hand (helix-loop-helix) motifs with an
      unique short loop, with a potential calcium-binding function. Itih-4 is expressed
      as a strong 3.1-kb transcript in liver, to a lesser extent in lung and heart
      tissue. RT-PCR demonstrates itih-4 mRNAs abundantly in liver, less in heart and
      brain, during mid-embryonic gestation. These results suggest that itih-4 is a
      potential regulator for extracellular matrix proteins and plays a role during
      early embryonic liver development.

PMID- 9602043
TI  - Effects of over- and under-expression of Cu,Zn-superoxide dismutase on the
      toxicity of glutamate analogs in transgenic mouse striatum.
AB  - Considerable evidence suggests that reactive oxygen species mediate the
      neurotoxic effects of ionotropic glutamate receptor activation. Accordingly, we
      have examined neuronal degeneration resulting from intrastriatal injection of
      quinolinic acid, an NMDA receptor agonist, and kainic acid in gene targeted and
      transgenic mice that under- or over-express copper, zinc superoxide dismutase
      (Cu,Zn-SOD; SOD-1). Elevated SOD-1 activity significantly protects against
      quinolinic acid and kainic acid neurotoxicity in the mouse striatum whereas
      reduced activity appears to potentiate neurotoxicity. Thus a 'gene-dose' effect
      of SOD-1 has been demonstrated with regard to excitotoxic mechanisms.

PMID- 9602044
TI  - The ontogeny of GABA- and glutamate-like immunoreactivity in the embryonic
      Australian freshwater crayfish, Cherax destructor.
AB  - The distribution and ontogeny of GABA- and glutamate-like immunoreactivity in
      embryos of the Australian freshwater crayfish Cherax destructor were investigated
      over the period from 30% development until hatching. GABA-like immunoreactive
      cells and fibres appeared first in the brain at 40-45% development. By 70%
      development, GABA-like immunoreactive cells were present in almost all ganglia,
      and GABA-like immunoreactive fibres were distributed extensively throughout the
      neuropil, commissures and connectives of the central nervous system, and were
      also found in peripheral nerve roots supplying the appendages and the abdominal
      musculature. In contrast, glutamate-like immunoreactivity did not appear in the
      central nervous system until 60-65% development. By the time of hatching, the
      distribution of glutamate-like immunoreactivity was restricted to discrete
      regions of neuropil and fibre staining in the thoracic and abdominal nerve cord,
      the abdominal musculature and the appendages. The precocious establishment of the
      extensive distribution of GABA-like immunoreactive neurons in the developing
      crayfish embryo is consistent with the possibility that these neurons play a
      trophic role in controlling or modulating the development of the nervous system.

PMID- 9602045
TI  - Structure and expression of a novel isoform of mouse FGF homologous factor (FHF)
      4.

PMID- 9602046
TI  - Increased expression of dendritic mRNA following the induction of long-term
      potentiation.
AB  - A small number of mRNAs, including Ca2+/calmodulin-dependent protein kinase II
      alpha-subunit (CamKIIalpha) mRNA and microtubule-associated protein 2 (MAP2)
      mRNA, are present in the dendrites of neurones as well as in the cell bodies. We
      show here that the induction of long-term potentiation (LTP) in the hippocampal
      perforant path/granule cell synapses in anaesthetised rats is associated with
      increased levels of CamKIIalpha mRNA and MAP2 mRNA in the granule cell dendrites
      after 2 h. Similarly, induction of LTP in the Schaffer collateral/CA1 pyramidal
      cell synapses in hippocampal slices maintained in vitro also results in elevated
      dendritic levels of CamKIIalpha mRNA and MAP2 mRNA 2 h later. In both models, the
      levels of various other mRNA species restricted to the cell body region were
      unaffected by the induction of LTP. Increased expression of dendritic CamKIIalpha
      mRNA and MAP2 mRNA appears to be a general feature of hippocampal plasticity,
      since it occurs following LTP induction in both the dentate gyrus and the CA1
      region. The elevation of mRNA levels in a restricted region close to the afferent
      synapses would allow a highly-localised enhancement of the synthesis of the
      corresponding proteins, providing an elegant mechanism for protein-synthesis
      dependent synaptic plasticity to maintain a high degree of anatomical
      specificity.

PMID- 9602048
TI  - Regional localization of specific [125I]leptin binding sites in rat forebrain.
AB  - Specific [125I]leptin receptor binding sites have been identified in choroid
      plexus (CP), but have eluded regional localization within the brain parenchyma.
      To optimize specific [125I]leptin binding in brain loci, we ran experiments
      varying the pH of incubation buffers. We found that specific [125I]leptin binding
      in CP was strikingly pH dependent with the most acidic buffer, pH 5.5, resulting
      in a greater than 100% increase over the amount of specific binding measured at
      pH 7.5. While low pH permitted detection of specific binding in parenchymal loci,
      clear pH dependency was only observed in the CP. In the caudate putamen (CauP), a
      locus with low specific binding, values for specific binding did not differ
      significantly across the range of pH conditions tested. Using incubation buffers
      at pH 6.0 in subsequent binding experiments, we localized specific [125I]leptin
      binding in several brain loci including thalamus and hypothalamus. In CP and
      thalamus, where the range of OD permitted analysis of binding parameters,
      [125I]leptin binding was saturable with increasing concentrations of unlabelled
      leptin. In all loci, specific [125I]leptin binding was insensitive to competition
      by high concentrations of other unlabelled compounds. Our results varying pH
      conditions of the incubation buffer suggest leptin receptors may be divided into
      subclassifications based on pH sensitivity of the specific binding. Furthermore,
      our results suggest that although densities are low, high affinity leptin
      receptors are present in neural loci implicated in food intake and energy
      balance, and are more widespread in the forebrain than previously determined.

PMID- 9602049
TI  - A chromo box gene from carrot (Daucus carota l.): its cDNA structure and
      expression during somatic and zygotic embryogenesis.
AB  - A cDNA clone, designated DcDB1, was isolated from a cDNA library prepared from
      embryogenic cell clusters of carrot (Daucus carota L.) and characterized. The
      cDNA (1416 bp) encoded for a protein of 392 amino acid residues that contained a
      conserved chromo domain. The chromo domain is a 37 aa region found in both the
      Polycomo gene product, which is a repressor of homeotic genes, and a
      heterochromatin protein 1 of Drosophila. This domain is postulated to function in
      the binding of proteins to chromatin. Genomic blot hybridization experiments
      suggested that the number of DcCB1 genes in the carrot genome is low. The level
      of DcCB1 mRNAs was high in somatic embryos at globular and heart-shaped stages
      but low in torpedo-shaped somatic embryos. The level of DcCB1 transcripts
      decreased during the formation of seeds. The existence of both homeo and chromo
      box genes in plants suggests that regulatory mechanisms of developmental genes in
      plants may resemble those in Drosophila.

PMID- 9602050
TI  - Extracellular potassium concentration regulates proliferation of immature
      cerebellar granule cells.
AB  - The present study examines the effect of depolarizing potassium concentrations on
      the proliferation of immature rat cerebellar neurons. Cells inoculated in serum
      free medium and 5 mM KCl (5 K) showed a high degree of 3H-thymidine incorporation
      that decreased 24-48 h after plating as differentiation began. During the first
      24 h after inoculation, cells grown in high potassium (25 K), showed a 34 +/- 3%
      increase (mean +/- S.E.M., n = 12) in 3H-thymidine incorporation as compared with
      the values observed in 5 K. After 24 h in vitro, cells grown in 25 K showed 23 +/
      3% (mean +/- S.E.M., n = 3) less DNA synthesis than those inoculated in 5 K. The
      increase in DNA synthesis due to 25 K was blocked by MgCl2 and nifedipine, but
      not by omega-conotoxin GVIA, suggesting that it is mediated by a Ca2+ influx via
      voltage-gated calcium channels (VGCC) of the L-subtype. High potassium-induced
      cell proliferation was blocked by the mitogen-activated protein kinase kinase
      (MEK1) inhibitor (PD98059, 75 microM). The number of neurons counted after 48 h
      in vitro in 25 K was 35-100% above of the number obtained with 5 K and this
      increase also was blocked by MgCl2 and nifedipine. These data support the
      hypothesis that depolarizing activity during neurogenesis plays a role in the
      modulation of cerebellar granule cells proliferation.

PMID- 9602051
TI  - Construction and analysis of a semi-quantitative energy profile for the reaction
      catalyzed by the radical enzyme galactose oxidase.
AB  - Galactose oxidase (GOase) is a mononuclear type 2 copper enzyme which oxidizes
      primary alcohols to aldehydes using molecular oxygen (RCH2OH + O2 = RCHO + H2O2).
      An unusual crosslink between tyrosine 272 and cysteine 228 provides a modified
      tyrosine radical site which acts as a ligand for the active site copper and is
      believed to act as a one-electron redox center. The single active site copper is
      believed to act as a second one-electron redox center. The use of the tyrosine
      one-electron redox center and the copper one-electron redox center allows removal
      of two electrons from alcohol substrate for subsequent transfer to molecular
      oxygen. Previously, we and others have proposed a detailed step-by-step radical
      mechanism for the reaction catalyzed by galactose oxidase. The catalytic cycle
      can be divided into two half reactions. The first half reaction entails transfer
      of two electrons and two protons from the alcohol substrate to the enzyme to form
      aldehyde product and two-electron-reduced enzyme (one electron at the tyrosine
      center and one at the copper center). The second half reaction entails transfer
      of two electrons and two protons from the two-electron-reduced enzyme to O2 to
      form H2O2 product and regenerate fully oxidized catalytically active enzyme ready
      for another catalytic cycle. In this paper, we describe the construction of a
      semi-quantitative energy profile for this radical mechanism. Several significant
      points emerge from this analysis. One point is the prediction that galactose
      oxidase should have an unusually low redox potential for copper, to our knowledge
      lower than any other redox active copper protein. Another point is that the
      distorted or entatic copper site causes the unusually low redox potential. A
      final point is that crosslinking of tyrosine 272 and cysteine 228 alters the
      redox properties of the tyrosine center to enhance catalysis compared to what
      would be expected for a normal tyrosine.

PMID- 9602052
TI  - Cyclooxygenase-2 is induced in brain blood vessels during fever evoked by
      peripheral or central administration of tumor necrosis factor.
AB  - Cyclooxygenase-2 (COX-2) is an inducible type of enzyme that is involved in
      prostaglandin biosynthesis. In the present study, we examined whether or not COX
      2 is involved in fever that is induced by tumor necrosis factor-alpha (TNF-alpha)
      and, if so, where in the brain COX-2 is induced by this factor. Intraperitoneal
      (i.p.) injection of TNF-alpha into rats evoked a fever that started 1 h after the
      TNF injection, peaked 3 h after the injection, and then gradually declined. The
      fever was suppressed by pretreatment with a COX-2-specific inhibitor. With a time
      course similar to that of fever, COX-2 mRNA was induced in brain blood vessels.
      On the other hand, in some of the telencephalic neurons, COX-2 mRNA was
      constitutively expressed under the normal condition; but its level gradually
      decreased during the course of fever. Fever was also evoked by an
      intracerebroventricular (i.c.v.) injection of TNF-alpha. This febrile response
      was also suppressed by a COX-2 specific inhibitor and was associated with the
      induction of COX-2 mRNA in the brain blood vessels. On the other hand, the
      telencephalic neurons did not show consistent change in COX-2 mRNA level after
      i.c.v. injection of TNF-alpha or saline. COX-2-like immunoreactivity was found in
      some cells of the brain blood vessels 3 h after the TNF-alpha injection by either
      i.p. or i.c.v. route. Most of the COX-2-like immunoreactive cells were
      endothelial cells since COX-2-like immunoreactivity was colocalized with von
      Willebrand factor, an endothelial cell marker, in the same cells. These results
      suggest that the brain blood vessels are the major sites where TNF-alpha enhances
      PG biosynthesis after peripheral as well as after central injection, and provides
      further evidence supporting the hypothesis that COX-2 induced in the brain blood
      vessels is involved in fever.

PMID- 9602053
TI  - Structure and expression of a cyst specific protein of Acanthamoeba castellanii.
AB  - The life cycle of Acanthamoeba is divided into a growth-division phase and two
      distinctive processes of cellular differentiation, termed encystment and
      excystment. Polyacrylamide gel electrophoresis revealed that a specific protein
      of 21 kDa in molecular weight occurs in the cyst, but not in the trophozoite
      stages of A. castellanii Neff strain. This cyst-specific protein, designated as
      CSP21, was purified from guanidine-HCl extract of cyst wall and anti-CSP21
      antibody was produced. Immunoblotting of proteins extracted from a variety of
      species of Acanthamoeba genus suggested that the antibody is specific for group
      II amoebae, therefore, providing a useful tool for Acanthamoebae taxonomy. A cDNA
      clone for A. castellanii CSP21 was isolated by immunoscreening of a cDNA
      expression library constructed from mRNA of amoebae at encysting stage. The
      deduced primary structure indicated that CSP21 is a hydrophilic protein showing
      no significant homology with peptides thus far published. RNA blot analysis
      showed that the expression of CSP21 mRNA was restricted within early stages of
      encystment, suggesting that the biosynthesis of CSP21 is regulated at mRNA level.

PMID- 9602054
TI  - Lateral ventricle injection of the protein synthesis inhibitor anisomycin impairs
      long-term memory in a spatial memory task.
AB  - Although protein synthesis inhibition has been shown to affect long-term memory
      in a wide variety of animal species, cases have been reported in which protein
      synthesis inhibition failed to affect memory consolidation [S. Wittstock, R.
      Menzel, Color learning and memory in honey bees are not affected by protein
      synthesis inhibition, Behav. Neural Biol., 62 (1994) 224-229.]. Most findings
      argue that the critical time for protein synthesis is during or immediately after
      training. However, other reports show a second time window, hours after training,
      where protein synthesis inhibition can cause amnesia [F.M. Freeman, S.P.R. Rose,
      A.B. Scholey, Two time windows of anisomycin-induced amnesia for passive
      avoidance training in the day-old chick, Neurobiol. Learn. Mem., 63 (1995) 291
      295.][G. Grecksch, H. Matthies, Two sensitive periods for the amnesic effect of
      anisomycin, Pharmacol. Biochem. Behav., 12 (1980) 663-665.]. In this study, we
      addressed two questions: (1) Is protein synthesis essential for spatial memory?
      and (2) At what injection time window(s) will protein synthesis inhibition cause
      spatial memory amnesia? We report that bilateral intraventricular microinjection
      of anisomycin (Ani) impairs consolidation of long-term memory, in the hippocampal
      dependent Morris water maze spatial memory task. Memory was impaired in a dose
      dependent manner without affecting short-term memory. Spatial memory was affected
      only if Ani was injected 20 min before performing the task and not in any other
      time window before or after the behavioral test. The inhibition did not affect
      pre-existing memories or the capability to memorize once the effect of the
      inhibition diminished.

PMID- 9602055
TI  - Ovulatory delay alters postnatal growth, behavior, and brain structure in rats.
AB  - To investigate the effect of a delay in ovulation on postnatal growth and
      development in resultant rat offspring, a 1-day ovulatory delay was induced by
      sodium pentobarbital, animals mated, and the offspring monitored. There were no
      differences between control and 1-day delayed offspring in the number of live or
      dead births, number of males or females, nor in the ratio of sexes. Delayed pups
      had a slightly lower birth weight, but then recovered to weigh more than controls
      by day 12. In the first two weeks post-parturition, delayed pups displayed an
      earlier ability to reorient themselves in a negative geotaxis test, but no
      differences by the righting reflex and reflex suspension tests. At postnatal day
      (pnd) 28, delayed pups exhibited decreased activity in a continuous corridor
      test, but no alterations in gait. At this time, the brains of delayed animals
      revealed thickening of cortical layers V plus VI. There were significant
      correlations between various developmental endpoints (body weight, negative
      geotaxis, continuous corridor activity, and gait) and the cortical layer
      thicknesses. The results indicate that ovulatory delay produces changes in brain
      cortical thickness, with correlative changes in growth and behavior. Although the
      mechanisms by which ovulatory delay alters postnatal development and brain
      structure are unknown, ovulatory delay may alter the uterine environment during
      early pregnancy.

PMID- 9602056
TI  - Ribonucleases from rat and bovine liver: purification, specificity and structural
      characterization.
AB  - The presence of four members of the pyrimidine-specific ribonuclease superfamily
      was demonstrated in rat liver. Three of them (RL1, RL2 and RL3) were purified and
      showed ribonuclease activity at pH 7.5 with yeast RNA as substrate. RL1 is
      identical to rat pancreatic ribonuclease (ribonuclease 1). N-terminal sequence
      analysis showed the presence of the native protein and several N-terminally
      degraded components. RL2 and RL3 were N-terminally blocked proteins. After acidic
      cleavage or CNBr digestion, several parts of their sequences were determined. RL2
      has high sequence similarity with neurotoxin-type ribonucleases (ribonucleases 2,
      3 and 6). The amino acid sequence of rat liver-type ribonuclease (ribonuclease 4)
      was determined from a liver cDNA library. It differs at about 20% of the amino
      acid positions from other mammalian liver-type ribonucleases. The sequence of a
      peptide of RL3 was identical to that derived from the cDNA sequence of the liver
      type ribonuclease. A contaminant of the RL3 fraction had a high sequence
      similarity with mouse and other mammalian angiogenins. Bovine, porcine and rat
      liver-type ribonucleases showed a strong preference for poly(U) over poly(C).
      This preference is a unique property of the liver-type enzymes of the
      ribonuclease superfamily.

PMID- 9602057
TI  - Role of central opioid receptor subtypes in morphine-induced alterations in
      peripheral lymphocyte activity.
AB  - Morphine has been shown to decrease proliferative responses of rat T-lymphocytes
      via central opioid receptors, however, the specific receptor subtype(s) mediating
      this effect have not been established. To determine the potential role of central
      mu opioid receptors in morphine-mediated suppression of T-lymphocyte
      proliferation, 20 nmol/2 microliters of either morphine sulfate or DAMGO (mu
      selective agonist) were administered into the lateral ventricle of freely moving
      Sprague-Dawley rats. Lymphocyte proliferative response to the polyclonal T cell
      mitogen concanavalin A (ConA), changes in splenic natural killer cell (NK)
      cytolytic activity, activation of the hypothalamic-pituitary-adrenal (HPA) axis
      and antinociception (tail-flick latency) were examined. Results indicated that
      like morphine, DAMGO decreased blood lymphocyte proliferative responses by 80%
      and elevated both tail-flick latency and plasma corticosterone when compared to
      saline-treated animals. The proliferation response of lymphocytes from the spleen
      or thymus and splenic NK cell activity were not significantly altered by either
      morphine or DAMGO treatment. The effects of DAMGO were determined to be dose
      dependent and completely antagonized by naltrexone pretreatment. Central
      administration of DPDPE (delta-selective agonist) and U-50488 (kappa-selective
      agonist) produced between 40-50% suppression of blood lymphocyte proliferation
      responses only at a dose five times greater (100 nmol) than DAMGO treatment,
      without altering antinociception or activation of the HPA axis. To determine the
      central opioid receptor subtype(s) involved in the effects of morphine, selective
      opioid antagonists were microinjected into the lateral ventricle prior to
      morphine treatment (6 mg/kg, s.c.). CTOP (mu-selective antagonist, 5 micrograms/2
      microliters) completely blocked the effects of morphine on all parameters
      measured, however, naltrindole (delta-selective antagonist, 2 micrograms/2
      microliters) or nor-binaltorphimine (kappa-selective antagonist, 73.5
      micrograms/2 microliters) failed to block the effects of morphine. Collectively,
      these results provide evidence that morphine acts primarily through central mu
      receptors to modulate peripheral blood lymphocyte proliferation responses.
      Further, the antinociception and blood lymphocyte effects show greater
      sensitivity to opioids than either natural killer cell cytolytic activity or
      activation of the HPA axis.

PMID- 9602058
TI  - Mouse procathepsin E gene: molecular organisation and chromosomal localisation.
AB  - A 15.6 kb genomic clone encompassing the mouse procathepsin E gene was isolated
      and mapped. Sequencing revealed that the gene consists of nine exons followed by
      a polyadenylation signal at the 3'-end. The 5'-flanking region appears to be a
      TATA-less promoter but contains a nucleotide sequence that matches perfectly with
      the consensus motif of an initiator element [S.T. Smale, Biochim. Biophys. Acta
      1351 (1997) 73-88.] to direct accurate initiation of transcription by RNA
      polymerase. This overlaps the site that was determined for the start of
      transcription. The absence of features considered typical of TATA-box regulated
      or housekeeping types of genes is consistent with the low levels of procathepsin
      E gene expression that are normally observed and might imply a unique sensitivity
      to or requirement for tissue-specific transcription factors that would account
      for the sporadic distribution of this aspartic proteinase in cells and tissues.
      The single copy of the procathepsin E gene was located on chromosome 1, near to
      that of mouse prorenin, a closely related aspartic proteinase involved in blood
      pressure regulation.

PMID- 9602059
TI  - RPE secreted proteins and antibody influence photoreceptor cell survival and
      maturation.
AB  - Proteins in media conditioned by retinal pigment epithelial cells (RPE-CM) and an
      antibody against these proteins (RPE-SP) were tested for their respective effects
      on rat retinal development in vitro and in vivo. Proteins of RPE-CM were
      separated in denaturing gels and evaluated by Western blot analysis. Retinal
      explants from postnatal day 2 (P2) rats were cultured in RPE-CM only or CM
      diluted with the RPE-SP antibody and, after 7 days, the explants were dissociated
      into single cells that were immunostained for opsin. RPE-CM or antibody was also
      injected into the vitreous of postnatal day 7 (P7) Long-Evans rats and analyzed 7
      and 21 days later. Electrophoretic analysis of RPE-CM predominantly showed 60-70
      kDa proteins; when these proteins were probed with RPE-SP antibody by Western
      blot, immunoreactive proteins were restricted to this narrow molecular weight
      range. In P2 retinal explant cultures supplemented with RPE-CM, long ganglion
      cell-like neurites were detected in 3 days. This activity was nullified in
      explant cultures grown in RPE-CM titrated with antibody, and these explants
      appeared to degenerate within 5 days. Over 80% of dissociated retinal cells from
      explants 7 days after treatment with RPE-CM expressed opsin, compared to only 20%
      of cells from explants grown in defined medium or serum. Retinas of P14 rats
      injected intravitreally with RPE-CM at P7 had increased numbers of ectopic
      photoreceptor cells within the inner nuclear layer when compared to retinas of
      sham-injected eyes. In contrast, retinas of eyes injected intravitreally with RPE
      SP antibody exhibited shorter outer (OS) and inner (IS) segments and thinner
      outer nuclear (ONL) and outer plexiform (OPL) layers than retinas of sham
      injected eyes. In conclusion, proteins in RPE-CM appeared to accelerate and
      maximize the development of rat photoreceptor cells in vitro, while intravitreal
      injections of its antibody caused an apparent retardation of outer segment
      maturation. These results suggest that a protein(s) secreted by RPE plays a key
      role in normal retinal development, particularly in photoreceptor cell survival
      and outer segment maturation.

PMID- 9602061
TI  - Cloning and characterization of the presenilin-2 gene promoter.
AB  - Mutations in the presenilin-2 (PS-2) have been shown to cause early onset
      Alzheimer's disease (AD) in a series of families known as the Volga Germans and
      in an unrelated Italian kindred. Expression of the PS-2 gene is regulated during
      AD, aging, development and brain injury. Although expressed primarily in neurons,
      enhanced levels of PS-2 have been reported in astrocytes activated by neuronal
      damage. Understanding the regulation of the PS-2 gene may thus provide an insight
      into its role in AD. We have isolated a 3635 bp DNA fragment that contains 2934
      bp of DNA sequence upstream from the PS-2 gene. Primer extension analysis was
      used to map three major transcriptional start sites within the PS-2 gene. The
      promoter sequence, upstream of each transcriptional start site, does not contain
      TATA or CAAT boxes but does contain several GC rich sites (Sp-1 and AP-2). A
      reporter gene construct containing the PS-2 promoter (PS2P, -2934 to +702)
      transfected into M17 cells drives basal transcription to 20% of the levels of the
      SV-40 viral promoter. Addition of NGF to PC-12 cells was found to upregulate the
      PS2P promoter and an NGF-responsive element was localized by deletional analysis
      between -403 and +13 within the promoter. Since the PS-2 gene has multiple start
      sites and the upstream sequence is GC rich with no TATA box, the PS-2 promoter is
      consistent with the GC class of 'housekeeping' genes.

PMID- 9602062
TI  - Necrogenic and regenerative responses of liver of newly weaned rats against a
      sublethal dose of thioacetamide.
AB  - The hepatocellular necrogenic and regenerative responses of newly weaned rats (21
      days old) to a sublethal dose of thioacetamide (6.6 mmol kg-1) were studied in
      comparison to adult (6-month old rats), in terms of liver injury, antioxidant
      defense systems and cell proliferation. Hepatocellular necrosis, detected by
      serum aspartate aminotransferase, was less severe in newly weaned rats than in
      adult animals and was parallel to previous changes in the activity of microsomal
      FAD monooxygenase system responsible for thioacetamide biotransformation. Liver
      damage in hepatocytes from newly weaned rats was also detected by the decreased
      levels of glutathione and protein thiol groups (47%, p < 0.001 and 52%, p < 0.001
      vs. untreated, respectively) and by the enhanced malondialdehyde production
      (334%, p < 0.001) and glutathione S-transferase activity (384%, p < 0.001). No
      significant differences were detected in these values when compared to adults.
      Changes in cytosolic and mitochondrial superoxide dismutase and catalase
      activities in hepatocytes from newly weaned rats at 24 h, following thioacetamide
      (49%, p < 0.001; 50% and 53%, p < 0.001 vs. untreated, respectively), were less
      severe against those in adult hepatocytes at 48 h of intoxication, and the
      increases in glutathione peroxidase and glutathione reductase activities were
      significantly lowered: 25% (p < 0.001) and 41% (p < 0.001), respectively. Post
      necrotic DNA synthesis in hepatocytes from newly weaned rats peaked at 48 h of
      intoxication, while in adults a more intense peak appeared at 72 h preceded by a
      sharp decrease in tetraploid population. These differences indicate that the
      lower necrogenic response against the same dose of thioacetamide in newly weaned
      rats may be due to the lower rate of thioacetamide biotransformation and to the
      earlier onset of cell division. Accordingly, the growing liver from newly weaned
      rats presents advantages against the necrogenic aggression of thioacetamide,
      first, because the diminished activity of its specific microsomal detoxification
      system, and second because the earlier increase in the proliferative response
      prevents the progression of injury permitting an earlier restoration of liver
      function.

PMID- 9602063
TI  - Expression of an ADP-ribosylation factor like gene, ARF4L, is induced after
      transient forebrain ischemia in the gerbil.
AB  - To elucidate the molecular mechanisms underlying post-ischemic phenomena
      including delayed neuronal death, we screened for genes which were induced in the
      hippocampus after transient global ischemia in the Mongolian gerbil by a
      differential display method, and cloned a gerbil homologue of human ADP
      ribosylation factor 4L (ARF4L). Although the physiological roles of ARF4L are
      unknown, it is likely that ARF4L participates in vesicle transport between the
      endoplasmic reticulum (ER) and Golgi complex as it contains a GTP binding site,
      myristoylation site and coatmer binding motif (KKXX). In situ hybridization
      analysis indicated that the expression of ARF4L mRNA was elevated in neurons of
      the dentate gyrus (DG) and CA1 regions. In DG, the signals were detected 3 h
      after ischemia and peaked at 6 h with subsequent gradual reduction. On the other
      hand, in the CA1 region where cell death occurs in this model, ARF4L mRNA was
      slightly detected from 1 to 2 days after ischemia but was absent after 3 days.
      Other vesicle transport-related genes such as ARF1, ARL4 and beta-COP were also
      induced after 5-min ischemia, suggesting that vesicle transport was activated in
      hippocampal neurons after ischemic stress. To determine the cause of the
      induction of ARF4L gene expression after transient ischemia, we examined the
      changes in ARF4L mRNA expression in HEK 293 cells under hypoxic conditions
      compared with HSP70. The expression of ARF4L mRNA was elevated at 12 h after
      hypoxia exposure, similarly to HSP70. These results will help to elucidate the
      association of upregulation of vesicle transport systems including ARF4L and
      stress responses of neurons after transient ischemia.

PMID- 9602064
TI  - The A/G polymorphism in the -78 position of the apolipoprotein A-I promoter does
      not have a direct effect on transcriptional efficiency.
AB  - A promoter polymorphism A/G at position 78 bp upstream of the transcription
      initiation site characterizes the human apolipoprotein A-I gene. Some studies
      correlated the higher Apo A-I levels or increased Apo A-I transcription
      efficiency with the A allele, while other studies did not confirm these results.
      We have investigated the in vitro effects of this transition on the
      transcriptional efficiency of ApoAI gene by creating two sets of identical
      constructs with the whole Apo A-I promoter, carrying the A or the G, linked to
      the complete ApoAI gene. The relative activity of the two promoter alleles was
      determined through a quantitative RT-PCR system after transient tranfections of
      human HepG2 cell line in basal state and after stimulation with retinoic acid or
      17beta-estradiol. Our results exclude differences in promoter activity linked to
      the A or G promoter alleles either in basal or in stimulated conditions. The data
      suggest that the A/G polymorphism does not directly affect the transcriptional
      efficiency of ApoAI gene, although it may be in linkage disequilibrium with other
      regulatory sequences and the combination of these elements may explain the
      contradictory results of the ApoAI gene expression.

PMID- 9602065
TI  - Mild hypothermia disturbs regional cerebrovascular autoregulation in awake rats.
AB  - The effects of mild hypothermia on regional CBF (rCBF) and autoregulation were
      investigated in 60 awake and spontaneously breathing Wistar rats. They were
      divided into normothermic (rectal and brain temperatures: 37.0 +/- 0.5 degrees C)
      and mildly hypothermic (33.0 +/- 0.5 degrees C) groups the temperature of the
      latter group was controlled by cooling a lead cast around each rat with ice-cold
      water. rCBF was measured by means of an autoradiographic technique with 14C
      iodoantipyrine. In normothermia, rCBF in most of the supratentorial cortical
      regions was maintained down to a mean arterial blood pressure (MABP) of 50 mmHg,
      produced by exsanguination, while rCBF in most of the brain stem regions showed a
      tendency to increase despite this reduction of MABP (predysautoregulatory
      overshoot of CBF). In the mildly hypothermic group, pre-exsanguination rCBF
      values were lower than those in normothermia, and rCBF in all brain regions
      declined significantly in proportion to decreasing MABP, produced by
      exsanguination. It is, therefore, concluded that mild hypothermia disturbs
      cerebrovascular autoregulation in awake rats.

PMID- 9602066
TI  - Effects of glucose deprivation in area CA1 of hippocampal slices from adult and
      juvenile rats.
AB  - The effects of glucose deprivation were studied in area CA1 of rat hippocampal
      slices obtained from adult and juvenile rats (postnatal days (PN) 6-8; 13-15; 20
      22). Ion-sensitive microelectrodes were employed to monitor baseline and stimulus
      induced changes in [Ca2+]0, [K+]0 and field potentials. In slices from juvenile
      animals, the decline of baseline [Ca2+]0 during glucose deprivation was delayed
      in comparison to adult slices. The minimum in [Ca2+]0 was reached in slices from
      adult rats after 50 +/- 8.5 min, in slices from PN 20-22 after 69 +/- 9 min, and
      in slices from PN 13-15 after 111 +/- 11 min. In slices from PN 6-8, [Ca2+]0 did
      not decrease significantly even during prolonged exposure of up to 4 h. Alvear
      stimulation failed to evoke any stimulus-induced responses in field potentials,
      rises in [K+]0 and decreases in [Ca2+]0 after the minimum in [Ca2+]0 was reached
      in slices from all age groups except for slices from PN 6-8. In the older age
      groups, afferent fibre stimulation still induced afferent volleys and small
      decreases in [Ca2+]0, which were about 20-30% of those under control conditions,
      suggesting that presynaptic fibres and endings maintained some of their
      functional properties even after prolonged glucose deprivation. In contrast,
      stimulation of the stratum radiatum failed to evoke synaptic responses in slices
      from PN 6-8, presumably due to a failure in synaptic transmission. These findings
      confirm that similar to hypoxia during the early postnatal stage, hippocampal
      neurons are much more resistant to glucose deprivation. The findings also show
      that during early postnatal development, glucose deprivation may result in a
      block of synaptic transmission independent of postsynaptic excitability.

PMID- 9602067
TI  - Acoustic transmission in the dentate nucleus. I. Patterns of activity to click
      and hiss; II. Changes in activity and excitability after conditioning.
AB  - Recordings were made from 95 units of the dentate nucleus of naive cats to
      determine if patterns of response to 70 dB clicks could be distinguished from
      those to another acoustic stimulus (a hiss) of approximately equal sound pressure
      level. Further studies of an additional 309 units were conducted to determine if
      unit excitability and the response to clicks changed after Pavlovian conditioning
      in which blink responses were elicited by the clicks as conditioned stimuli. Over
      50% of units tested before conditioning responded to click or hiss with increased
      activity, and 8% responded in the first 4-8 ms after the onset of the rapidly
      rising click. Cross-correlation of the respective 160 ms poststimulus histogram
      averages of mean activity showed dissimilar patterns of response to clicks and
      hisses (Pearson product-moment correlation coefficient + 0.02). Thus the averaged
      population responses distinguished these stimuli. In addition, individual cells
      were found in each behavioral state that responded selectively to either click or
      hiss. After conditioning with click as the conditioned stimulus, the number of
      units responding in the first 4-8 ms to click increased to 23%. The mean
      magnitude of activity 4-8 ms after presenting the click increased after
      conditioning but not after sensitization produced by backward pairing of the
      stimuli used for conditioning. After backward pairing only 6% of the units
      responded in the first 4-8 ms to click. The changes in activity after
      conditioning were accompanied by increases in neural excitability to
      intracellularly applied depolarizing current. In contrast with the changes in
      activity, the increases in neural excitability were also found after backward
      pairing. We conclude that short as well as long latency acoustic transmissions to
      click change in the dentate nucleus after conditioning, that changes in response
      to click are expressed in 4-8 ms responsive cells, and that many of these cells
      have different patterns of spike activity in response to click and hiss. The
      findings support the hypothesis that the dentate nucleus can play a significant
      role in short as well as long latency, adaptive acoustic transmission that can
      enhance the response to an acoustic signal used as a Pavlovian conditioned
      stimulus.

PMID- 9602068
TI  - Characterisation of the mouse homologue of CD151 (PETA-3/SFA-1); genomic
      structure, chromosomal localisation and identification of 2 novel splice forms.
AB  - CD151 (PETA-3/SFA-1) is a member of the Transmembrane 4 Superfamily (TM4SF) of
      cell-surface proteins and, like other TM4SF members CD9 and CD63, is expressed by
      platelets, megakaryocytes and endothelial cells. The precise function of CD151 is
      unknown however complexes containing CD151 and beta1 integrins have been isolated
      from a number of cell systems and studies using anti-CD151 monoclonal antibodies
      have suggested a role in transmembrane signalling and cell adhesion. To further
      investigate the function of CD151 we have determined the genomic organisation of
      mouse CD151 (Cd151). Cd151 spans 4 kb and contains six coding region exons. Using
      5' RACE and reverse transcriptase-polymerase chain reaction (RT-PCR) we have
      identified three 5' UTR splice variants which arise through alternate splicing of
      three exons. Splice variants were detected in a number of mouse tissues by RT
      PCR. Analysis of the Cd151 genomic structure reveals a high degree of structural
      conservation with other TM4SF molecules supporting the theory that family members
      have arisen from gene duplication of a common ancestral gene. Cd151 maps to
      chromosome 7, in close linkage to the p gene (OCA2 in humans), and helps define a
      boundary in the human/mouse homology relationships.

PMID- 9602069
TI  - The modulatory role of nitric oxide in the regulation of proenkephalin and
      prodynorphin gene expressions induced by kainic acid in rat hippocampus.
AB  - The effect of L-arginine (L-ARG), a nitric oxide donor, or Nomega-nitro-L
      arginine (L-NAME), a nitric oxide synthase inhibitor, on the regulation of kainic
      acid (KA)-induced proenkephalin (proENK) and prodynorphin (proDYN) mRNA
      expressions in rat hippocampus was studied. The proENK and proDYN mRNA levels
      were markedly increased 6 h after KA (10 mg/kg, i.p.) administration. The
      elevations of both proENK and proDYN mRNA levels induced by KA was effectively
      inhibited by pre-administration of L-ARG (400 mg/kg, i.p.), but was not affected
      by pre-treatment with L-NAME (200 mg/kg, i.p.). The blockade of KA-induced proENK
      and proDYN mRNA levels by the pre-treatment with L-ARG was well correlated with
      proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, JunD, JunB, and c-Jun, as
      well as AP-1 and ENKCRE-2 DNA binding activities. The pre-administration with L
      NAME further increased KA-induced c-jun and c-fos mRNA levels in addition to
      their protein product levels, although the pre-treatment with L-NAME did not
      affect KA-induced FosB, Fra-2, JunB, and JunD protein levels at 6 h after
      treatment. In addition, the pre-administration with L-NAME further increased the
      KA-induced AP-1 and ENKCRE-2 DNA binding activities. Our results suggest that L
      ARG plays an important role in inhibiting KA-induced proENK or proDYN mRNA
      expression, and its inhibitory action may be mediated through reducing the proto
      oncoprotein levels, such as c-Fos, Fra-2, FosB, c-Jun, JunD, and JunB. In
      addition, L-NAME potentiated the c-Fos or c-Jun gene expression, as well as AP-1
      or ENKCRE-2 DNA binding activity. However, these increases did not show the
      potentiative effect on KA-induced increases of proENK and proDYN mRNA level.

PMID- 9602070
TI  - Analysis of human serum albumin variants by mass spectrometric procedures.
AB  - A new strategy for the structural characterisation of human albumin variants has
      been developed which makes extensive use of mass spectrometric methodologies. The
      rationale behind the method is to provide a rapid and effective screening of the
      entire albumin structure. The first step in this strategy consists in the attempt
      to determine the accurate molecular mass of the intact variant by electrospray
      mass spectrometry often providing a first indication on the presence of the
      variant. An HPLC procedure has been developed io isolate all the seven fragments
      generated by CNBr hydrolysis of HSA in a single chromatographic step. A rapid
      screening of the entire albumin structure is achieved by the ESMS analysis of the
      peptide fragments and the protein region(s) carrying the structural abnormality
      is identified by its anomalous mass value(s). Mass mapping of the corresponding
      CNBr peptide, either by Fast Atom Bombardment Mass Spectrometry (FABMS) or by
      Matrix Assisted Laser Desorption Ionisation Mass Spectrometry (MALDIMS), leads to
      the definition of the site and the nature of the variation. This combined
      strategy was applied to the structural characterisation of three HSA genetic
      variants and provided to be an effective procedure for the rapid assessment of
      their structural modifications showing considerable advantages over the classical
      approach.

PMID- 9602071
TI  - The developmental profile of the corticotropin releasing factor receptor (CRF2)
      in rat brain predicts distinct age-specific functions.
AB  - Corticotropin releasing factor (CRF) activates two known receptor types, CRF1,
      and CRF2. In the adult rat brain, CRF2 has a distinct distribution pattern,
      suggesting that it may mediate functions exclusive of CRF1. The goal of this
      study was to determine the age-dependent distribution of CRF2-messenger RNA (CRF2
      mRNA) in the rat brain. Brains from rats sacrificed under stress-free conditions
      on fetal days (F) 15, 16, 17 and 19, and postnatal days 1, 3, 5, 7, 9, 12, 15,
      25, 49, and 90 (adult) were analyzed using semiquantitative in situ hybridization
      histochemistry. The onset and distribution of CRF2-mRNA in the developing rat
      brain revealed important differences from the adult expression pattern: earliest
      expression of CRF2-mRNA was observed in the ventromedial hypothalamus (VMH) on
      F16. High levels of CRF2-mRNA were present in the fronto-parietal cortex in the
      fetal and early postnatal brain but not later. Conversely, no CRF2-mRNA was
      detectable in the ventroposterior (lateral and medial) thalamic nuclei prior to
      postnatal day 7. Distinct developmental profiles of CRF2-mRNA were also observed
      in the lateral septum, medial, basal and cortical amygdala nuclei, and in several
      hippocampal fields. In conclusion, CRF2 is expressed in the hypothalamus on F16,
      prior to the detection of CRF itself in the paraventricular nucleus. The
      differential levels and distributions of CRF2-mRNA in hypothalamic and limbic
      brain regions indicate a precise regulation of this receptor's expression during
      development, as shown for CRF1. Regulation of the levels of CRF2 may modulate the
      effects of CRF (and related ligands) on target neurons, consistent with
      differential maturation of the functions mediated by this receptor.

PMID- 9602072
TI  - Tyrosine-533 of rat dopamine transporter: involvement in interactions with 1
      methyl-4-phenylpyridinium and cocaine.
AB  - To improve our understanding of structure-function relationships for
      neurotransmitter transporters, we performed site-directed mutagenesis of the rat
      dopamine transporter (DAT) and assessed the functions of the mutants in
      transiently-expressing COS cells. Tyrosine-533 of rat DAT lies in the 11th
      transmembrane region, where the corresponding amino acid of human DAT is
      phenylalanine. Alanine substitution of tyrosine-533 (Y533A) conferred an
      increased affinity for 1-methyl-4-phenylpyridinium (MPP+). Phenylalanine
      substitution of tyrosine-533 (Y533F) increased the velocity of MPP+ uptake but
      decreased DAT's affinity for MPP+. Cocaine's potency in inhibiting dopamine
      uptake was unchanged with Y533A, but increased with Y533F. Differences in the
      uptake kinetics and inhibitory potency of cocaine between rat and human DATs were
      similar to the differences observed between the wild-type and Y533F mutants DATs.
      Tyrosine-533 may be important for the DAT function and for species differences in
      transporter functions, including differential sensitivities to cocaine and 1
      methyl-1,2,3,6-tetrahydropyridine (MPTP) in humans and rats.

PMID- 9602073
TI  - Measurement of receptor-mediated functional activation of G proteins in
      postmortem human brain membranes.
AB  - Guanine nucleotide-binding regulatory proteins (G proteins) play a pivotal role
      in receptor-mediated transmembrane signal transduction, and have been implicated
      in modes of action of psychotropic drugs as well as in pathogenesis of
      psychiatric disorders. In the present investigation, functional activation of G
      proteins coupled with several receptors, in particular with GABAB receptors, was
      assessed by agonist-induced stimulation of high-affinity GTPase, an enzyme that
      is intrinsic to alpha subunit of G protein, in postmortem human frontal cortical
      membranes. High-affinity GTPase activity was stimulated by GABA as well as (+/-)
      baclofen, a selective GABAB receptor agonist, with EC50 values of 60-150 and 10
      40 microM, respectively, in a Mg(2+)-dependent manner. The (+/-)-baclofen
      stimulated response was antagonized by the selective GABAB receptor antagonist, 2
      hydroxy-saclofen, in a competitive manner with a KB value of 59 microM. Although
      the maximal percent increase above basal value (% Emax) for GABAB receptor
      mediated high-affinity GTPase activity was varied from subject to subject, % Emax
      values for both agonists were highly correlated with each other, and replicable
      and stable in a given subject, indicating that this measure is trustworthy as an
      index of functional coupling between receptors and G proteins in future studies
      at the aim of elucidating possible alteration of receptor/G protein interaction
      in psychiatric disorders. The % Emax values for GABAB receptor-mediated responses
      were correlated inversely with brain storage duration, which should be critically
      considered in postmortem studies. The increases in high-affinity GTPase activity
      stimulated by several agonists other than GABAB receptor agonists seemed too low
      to quantify for making a comparison in future studies.

PMID- 9602074
TI  - The Streptococcus agalactiae hylB gene encoding hyaluronate lyase: completion of
      the sequence and expression analysis.
AB  - We report the cloning, sequencing and expression analysis of the Streptococcus
      agalactiae strain 4755 hylB4755 allele, the first chromosomally-encoded
      streptococcal hyaluronate lyase gene to be cloned and sequenced completely. This
      gene lies in a region homologous to that found in S. mutans, between the mutX and
      rmlB genes, a region involved in the synthesis of the serotype c-specific
      polysaccharide antigen of this organism. Sequencing of hylB4755 revealed a 3216
      bp open reading frame that encodes a 121.2-kDa polypeptide possessing a 30-amino
      acid signal sequence which was theoretically predicted and experimentally
      confirmed. A recombinant plasmid, pHYB100, containing hylB4755 together with its
      promoter and terminator was constructed and used to analyze the expression of the
      gene in Escherichia coli. In Northern hybridization experiments, hylB4755 was
      found to be transcribed as 3.3-kb monocistronic mRNA from its own promoter which
      exhibits an extended, sigma70-like 10 consensus sequence. Transcript mapping by
      primer extension analysis placed the major transcription initiation site leading
      to the longest transcript 38 bp upstream of the translational initiation codon,
      ATG. E. coli TG1(pHYB100) efficiently synthesized hyaluronan-cleaving enzyme
      activity at approximately 7000 working units/109 cells, with lyase activity
      detectable in all principle cellular locations. Zymography and Western analysis
      identified functional activity in TG1(pHYB100) to be associated with
      approximately 118, 110 and 94-kDa polypeptides, with the two low molecular weight
      species constituting the major components of the enzyme purified from the culture
      supernatant fluid of S. agalactiae 4755. The 118-kDa form was shown to represent
      the undegraded mature enzyme, whereas the smaller species are likely to arise
      from proteolytic cleavage in the N-terminal part of the mature protein. The
      HylB4755 protein showed extensive sequence identity to the homologous enzymes
      from S. agalactiae 3502 and S. pneumoniae characterized by others but sequence
      comparisons clearly show that incomplete genes truncated at their 5' ends had
      been isolated from these two organisms.

PMID- 9602075
TI  - Specific vanilloid responses in C6 rat glioma cells.
AB  - Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific
      vanilloid receptors on sensory neurons. Here, we describe specific vanilloid
      responses in rat C6 glioma cells. Capsaicin and RTX stimulated 45Ca uptake in a
      similar fashion to that found for cultured rat dorsal root ganglion neurons
      (DRGs); this response was antagonized by the antagonists capsazepine and
      ruthenium red. As in DRGs, pretreatment of C6 cells with capsaicin or RTX
      produced desensitization to subsequent stimulation of 45Ca uptake. The potency
      for desensitization by RTX in the C6 cells corresponded to that for 45Ca uptake,
      whereas in DRGs it occurred at significantly lower concentrations corresponding
      to that for the high affinity [3H]RTX binding site. Consistent with this
      difference, in C6 cells we were unable to detect [3H]RTX binding. These
      characteristics suggest the presence of C-type but not R-type vanilloid receptors
      on C6 cells. After 2 day treatment, capsaicin but not RTX inhibited the
      proliferation and altered the differentiation of the cells and produced
      apoptosis. In the long term experiments, capsazepine, instead of antagonizing the
      effect of capsaicin, acted as an agonist. Moreover, capsazepine displayed these
      effects with higher potency than that of capsaicin. The different potencies and
      structure activity relations suggest a distinct mechanism for these long-term
      vanilloid effects. Our finding that C6 cells can respond directly to capsaicin
      necessitates a reevaluation of the in vivo pathway of response to vanilloids, and
      highlights the importance of the neuron-glial network.

PMID- 9602076
TI  - Chronic exposure to either somatostatin (SS) or octreotide, a long-lasting SS
      analogue, affects SS expression in the postnatal visual cortex of the rat.
AB  - The peptide somatostatin (SS) is widely distributed in the mammalian brain where
      it modulates neuronal activity through interactions with specific membrane-bound
      receptor subtypes (ssts). Five different ssts were characterized so far (sst1-5)
      and their selective agonists were developed on the basis of their binding
      specificity. SS and ssts are transiently expressed in the developing brain,
      suggesting a functional role of somatostatinergic systems in neuronal maturation.
      In the present study, we investigated the effects of chronic exposure to either
      the SS synthetic analogue, SS-14 or octreotide (a long-acting sst2-preferring
      analogue) on the maturation of SS-immunoreactivity (-ir) in the primary visual
      cortex of the rat. SS-ir maturation was investigated both by an evaluation of the
      number of SS-immunoreactive cells and by radioimmunoassay (RIA) to measure the
      levels of SS in the postnatal visual cortex. In the visual cortex of normal rats,
      the number of SS-positive cells markedly increased during the second postnatal
      week and then significantly decreased until the adult value was reached at the
      third week. Early and repeated intracerebroventricular (i.c.v.) injections of
      either SS-14 or octreotide prevented the increase in the number of SS-positive
      cells, with adult values reached at the end of the first postnatal week.
      Similarly, administration of either SS-14 or octreotide significantly decreased
      the SS content of the visual cortex, measured at the end of the second postnatal
      week. These results show that high local concentrations of either SS-14 or
      octreotide interfere with SS expression in developing cortical neurons in a
      restricted postnatal period.

PMID- 9602077
TI  - Autoradiographic mapping of cerebral blood flow responses to cholinergic
      stimulation of the rat substantia innominata: modulatory effect of galanin.
AB  - In order to analyze the precise cerebrovascular effects of a specific cholinergic
      stimulation of the rat substantia innominata and their modulation by galanin,
      cerebral blood flow was measured by the [14C]-iodoantipyrine autoradiographic
      method in anesthetized (urethane and alpha-chloralose), artificially ventilated
      male Sprague-Dawley rats that received a microinjection into the substantia
      innominata of saline (n = 7), or 63 pmol of galanin (n = 8), or 50 nmoles of
      carbachol (n = 6) or a coinjection of carbachol and galanin (n = 8). Significant
      carbachol-induced cerebral blood flow increases were noted in ipsilateral
      cortices (+36%, p < 0.01 in the cingulate to +82%, p < 0.01 in the parietal
      somatosensory cortices), but also in ipsilateral hippocampus and ipsilateral
      thalamus. These cerebral blood flow increases were abolished by the coinjection
      of carbachol and galanin, while infusions of galanin alone failed to affect
      cerebral blood flow. Cholinergic stimulation of the substantia innominata
      represents thus a good model for the analysis of the detailed pharmacological
      properties of the cholinergic vasodilatatory basalocortical system. The existence
      of an inhibitory galaninergic modulation of this system could be of particular
      interest, in terms of cerebrovascular reactivity, in various neurodegenerative
      states.

PMID- 9602078
TI  - Identification of heparin-binding stretches of a naturally occurring deleted
      variant of hepatocyte growth factor (dHGF).
AB  - A deleted variant of hepatocyte growth factor (dHGF) is a naturally occurring
      major variant of HGF, which lacks five consecutive amino acid residues in the
      first kringle domain. While both HGF and dHGF bind to heparin, the residues
      involved in the binding to heparin have not been identified in either protein. To
      identify the residues involved in the binding, we made a series of dHGF mutants
      in which basic residues in the N-terminal and the first kringle domains were
      replaced with alanine residue. The analysis of heparin-binding ability revealed
      that three stretches, 42RCTRNK in the hairpin loop structure, and 2RKRR and
      27KIKTKK in the N-terminal basic region, are involved in the binding. Alanine
      substitution of each basic residue except 3K and 27K in the stretches reduced the
      heparin-binding ability of dHGF, and the decrease was additive. Conversely,
      lysine substitution of 37D, 38Q or 64Q in the N-terminal domain increased heparin
      binding ability. These results suggest that stretches distant from each other in
      the primary structure come into close proximity when the polypeptide folds into
      protein, and form a heparin-binding site with clusters of basic residues.

PMID- 9602079
TI  - Gene expression in activated brain microglia: identification of a proteinase
      inhibitor that increases microglial cell number.
AB  - Microglia, the intrinsic immune cells of the central nervous system, are
      activated in a variety of inflammatory brain diseases in which they play a
      pathogenetic role. However, mechanisms underlying activation are largely unknown.
      To begin elucidating molecular mechanisms associated with activation, we
      characterized the pattern of gene expression in virtually pure dissociated
      microglial cultures, using RT-PCR differential display. Microglia were activated
      with bacterial lipopolysaccharide (LPS), a traditional stimulant, and the profile
      of gene expression was compared to that in basal, control cultures. Activation
      resulted in altered expression of six genes. The cDNAs were isolated, sequenced
      and characterized. Homology searches identified three novel genes, and two that
      exhibited very high sequence similarity to the gene encoding squamous cell
      carcinoma antigen (SCCA). SCCA (1 and 2) are tandemly arranged genes that encode
      two serine proteinase inhibitors (serpins). SCCA has been detected exclusively in
      cancer cells, and is a plasma marker for squamous cell carcinoma. Immunoblot
      analysis indicated that gene expression was accompanied by a 5-fold increase in
      the synthesis of SCCA protein in LPS-activated microglia. To assess potential
      biological actions of the SCCA serpins, SCCA1 protein was added to cultures.
      SCCA1 altered microglial morphology, and elicited a dramatic, 5-fold increase in
      cell number within 72 h. The effects appeared to be cell-specific, since the
      protein had no effect on other cell types: cortical astrocytes and neurons from
      cortex or basal forebrain were unaffected. We tentatively conclude that SCCA1 may
      play a cell-specific role in increasing cell number, a critical early step in
      microglial activation and brain inflammation. More generally, differential
      display of genes in the microglial model system may help define patterns of
      expression associated with CNS disease, thereby identifying pathogenetic
      mechanisms and new therapeutic targets.

PMID- 9602080
TI  - Calretinin immunoreactivity in the anterior olfactory nucleus of the rat.
AB  - Calretinin-immunoreactive structures in the anterior olfactory nucleus of the rat
      were studied using a polyclonal antibody, which does not cross-react with the
      highly homologous calcium-binding protein calbindin-D28k, and the avidin-biotin
      peroxidase technique. Calretinin-immunopositive neurons were found in all regions
      of the anterior olfactory nucleus, with the highest number in the medial
      subdivision and dorsal transition area. The immunostained neurons, although
      morphologically heterogeneous, demonstrated typically small size. In addition to
      neuronal somata, calretinin-immunopositive fibres and terminals, some of them
      forming basket-like arrangements surrounding immunonegative neurons, were
      observed. Although calretinin and calbindin-D28k colocalize in several brain
      regions, and both proteins showed an extensive overlap in the anterior olfactory
      nucleus, immunostained semithin sections demonstrated that calretinin does not co
      localize with calbindin-D28k in this nucleus.

PMID- 9602081
TI  - The effects of heme modification on reactivity, ligand binding properties and
      iron-coordination structures of cytochrome P450nor.
AB  - Artificial cytochrome P450nors (nitric oxide reductase) were prepared by
      replacing the native protoheme with various 2,4-substituted hemes: meso-, deutero
      , and diacetyldeutero-hemes. For these samples, the ratio of low spin/high spin
      states of the ferric resting enzyme were varied, indicating that the coordination
      of the water molecule at the iron sixth site was affected by the electron
      withdrawing capacities of the heme 2,4-substituents. The binding of the water
      molecule reduces the rate of binding of nitric oxide (NO) to the ferric iron. In
      addition, the reduction reaction of the ferric-NO complex with NADH, which
      constitutes the second step in the NO reduction, was facilitated by the electron
      withdrawing capacity of 2,4-substituents. Consequently, proto- (native-) P450nor
      exhibited the highest overall enzymatic activity (NO reduction activity), while
      the enzymes containing diacetyl-, deutero-, and meso-hemes had considerably lower
      activities, since the NO reduction activity is determined by a balance of the
      reaction rates of the above two steps. The optical absorption spectra of the
      ferric-NO and the ferrous-CO complexes of the reconstituted enzymes show that the
      electron density on the heme in both states was modulated by the substituent
      groups. However, the resonance Raman spectral measurements showed that the Fe-NO
      and N-O stretching frequencies in the ferric-NO complex were insensitive to the
      electron density of the heme while the Fe-CO and C-O stretching frequencies in
      the ferrous-CO complex were sensitively varied by the electron withdrawing
      capacity of the 2,4-substituent. The differences are discussed in terms of the
      difference in the iron-ligand bond characters between the ferric-NO and the
      ferrous-CO complexes.

PMID- 9602082
TI  - A novel assay for retinoic acid catabolic enzymes shows high expression in the
      developing hindbrain.
AB  - We have employed a novel technique that determines the relative capacity of
      tissues to catabolize all-trans retinoic acid (RA) to a metabolite incapable of
      activating a RA reporter cell line. This assay uses the microsomal fraction of
      tissues from the developing mouse and detects a pathway which requires NADPH and
      is inhibitable by ketoconazole, suggesting that a cytochrome P450-dependent
      enzyme may be required. High catabolic activity was detected transiently in the
      developing cerebellum which peaked at postnatal day 2. The medulla oblongata was
      the only other CNS region with high catabolic capacity, its earlier expression
      peak, between embryonic days 16 and 17, likely reflecting its earlier maturation.
      In the CNS, the hindbrain is exceptional in its high expression of RA catabolic
      enzymes, suggesting a unique function for regulated RA levels in this region.

PMID- 9602083
TI  - Differential role of specific PKC isoforms in the proliferation of glial cells
      and the expression of the astrocytic markers GFAP and glutamine synthetase.
AB  - In this study, we explored the role of specific protein kinase C (PKC) isoforms
      in glial cell proliferation and on the expression of the astrocytic markers GFAP
      and glutamine synthetase using C6 cells as a model. Analysis of the expression of
      the various PKC isoforms in control and differentiated C6 cells revealed
      differences in the expression of specific PKC isoforms. Undifferentiated C6
      cells, which express low levels of GFAP and glutamine synthetase (GS), have high
      levels of PKCalpha and delta, whereas differentiated C6 cells, which express
      higher levels of both GFAP and GS have lower levels of PKCalpha and delta and
      higher levels of PKCgamma, theta and eta. Using C6 cells overexpressing specific
      PKC isoforms, we examined the role of these isoforms on the proliferation and
      differentiation of C6 cells. Cells overexpressing PKCalpha displayed a reduced
      level of GFAP, whereas GS expression was not affected. On the other hand, cells
      overexpressing PKCdelta showed reduced GS expression but little effect on GFAP.
      Finally, cells expressing PKCgamma displayed a marked increase in the levels of
      both GFAP and GS. The proliferation of C6 cells was increased in cells
      overexpressing PKCalpha and epsilon and decreased in cells overexpressing
      PKCgamma, delta and eta. The results of this study suggest that glial cell
      proliferation and astrocytic differentiation can be regulated by specific PKC
      isoforms that selectively affect cell proliferation and the expression of the two
      astrocytic markers GFAP and GS.

PMID- 9602084
TI  - Epileptogenesis induced by rapidly recurring seizures in genetically fast- but
      not slow-kindling rats.
AB  - A brief period of rapidly recurring hippocampal seizures can lead to the
      progressive development of a permanent increase of seizure susceptibility over
      several weeks, so-called 'delayed kindling'. We have analyzed seizure parameters
      critical for the induction of delayed kindling in two strains of rats
      characterized by fast and slow rates of traditional kindling, respectively. Forty
      seizures were produced during about 3 h by electrical kindling stimulations every
      5 min in the ventral hippocampus. The fast rats displayed several generalized
      convulsions and had long periods of epileptiform activity, whereas the slow
      animals only exhibited brief, focal seizures. Changes in excitability were
      determined after 4 weeks using five test stimulations, and 2 weeks later by
      subjecting all animals to traditional hippocampal kindling. The fast rats showed
      clearly enhanced responsiveness at these time points, whereas no evidence of
      permanently increased seizure susceptibility was obtained in the slow rats. Our
      data indicate that the long-lasting stimulus-evoked seizures are mainly
      responsible for inducing delayed kindling, whereas the number of seizure events
      or generalized convulsions, and the total duration of epileptiform activity are
      less important. We hypothesize that long seizure episodes may be necessary to
      trigger the cascade of gene changes regulating the development of epilepsy.

PMID- 9602086
TI  - Circular dichroism analysis of the glucan binding domain of Streptococcus mutans
      glucan binding protein-A.
AB  - The glucan binding domain (GBD) of the glucan binding protein-A (GBP-A) from the
      cariogenic bacterium Streptococcus mutans was studied using circular dichroism
      (CD) analysis, Chou-Fasman-Rose secondary structure prediction, and absorption
      and fluorescence spectroscopy. Our data show that the binding domain undergoes a
      conformational shift upon binding to the ligand dextran. The CD spectrum shows
      two positive bands at 280 nm and 230 nm which were assigned to aromatic residues.
      The 230-nm band was seen at 20 degrees C and 30 degrees C, lost intensity at 40
      degrees C, and was eliminated at 45 degrees C coinciding with complete
      denaturation. The protein was stable at physiological pH, but precipitated at pH
      5. A pH of 10 changed the secondary structure but had no effect on the 230-nm
      band. Analysis of the CD data in the far UV using the SELCON computer program
      revealed a high content of beta-sheets and a lack of alpha-helical structures.
      Secondary structure prediction based on the amino acid sequence of GBD agreed
      with the CD analysis. The fluorescence emission maximum at 339 nm suggested that
      the majority of the tryptophans were located in the interior of the protein. This
      maximum shifted to higher energy upon binding to the ligand dextran.

PMID- 9602087
TI  - Differences in D2 dopamine receptor binding in the neostriatum between cats
      hemidecorticated neonatally or in adulthood.
AB  - In order to study differences in response to neocortical injury sustained at
      different ages at the neurotransmitter level, we examined the density in D2
      dopamine receptors in the neostriatum of cats hemidecorticated neonatally (N = 4)
      or in adulthood (N = 4), as well as in intact brains (N = 6). Receptor densities
      were measured using quantitative autoradiography and [3H]-spiperone binding in 12
      regions of the neostriatum and nucleus accumbens septi. We found that the
      anterior lateral caudate nucleus on both sides of the brain contained a higher D2
      receptor density in neonatal-lesioned as compared to adult-lesioned brains.
      Ipsilateral to the lesion, the increase was 101% (P < 0.05) and contralaterally
      it amounted to 77% (P < 0.05). Moreover, this region of the ipsilateral caudate
      nucleus of neonatal-lesioned cats tended to be more densely labeled than that of
      intact brain by 58% (P < 0.1). D2 receptor densities in adult-lesioned cats did
      not differ from that of intact controls. Comparison of these data with those of a
      former morphological study using the same animals suggested that this bilateral
      elevation of D2 receptor density in neonatally lesioned brains represents a
      higher mean density of binding sites per neuron. The elevation in the neonatal
      lesioned cats might be a response of the striatum to neuroplastic changes in the
      striatal neuropil, including the corticostriatal afferents, since such changes
      are different in neonatal- as compared to adult-lesioned cats.

PMID- 9602088
TI  - Corticocortical connections between frontal periarcuate regions and visual areas
      of the superior temporal sulcus and the adjoining inferior parietal lobule in the
      macaque monkey.
AB  - In macaque monkeys, corticocortical connections between distinct parietotemporal
      visual areas (areas MST-FST, DP, and 7a) and frontal periarcuate areas are
      studied using tritiated aminoacids and WGA-HRP. While labeling within the banks
      of the principal sulcus, the dorsal part of the arcuate concavity, and the banks
      of the upper arcuate limb were present in both 7a and MST-FST injected animals;
      in the latter cases, additional projections were found towards frontal regions
      including the dorsomedial frontal cortex and the posterior bank of the arcuate
      ventral limb. Our results point to widespread frontal connections of the MST-FST
      complex, involving both prefrontal and premotor cortical regions.

PMID- 9602089
TI  - Activation of the MAP kinase cascade by histone deacetylase inhibitors is
      required for the stimulation of choline acetyltransferase gene promoter.
AB  - We previously described that the major promoter (M) of human choline
      acetyltransferase (ChAT) gene is activated by three inhibitors of histone
      deacetylase, butyrate, trichostatin and trapoxin, in transfected CHP126
      neuroepithelioma cells. We now show that trapoxin and butyrate triggered a rapid
      and transient phosphorylation of ERK1/2 kinases, that was suppressed by PD98059,
      a highly specific inhibitor of MAP kinase kinase MEK1. The stimulation of ChAT
      promoter activity by trapoxin or butyrate did not require ongoing protein
      synthesis, and was suppressed by PD98059. The overexpression of dominant negative
      mutants of H-ras or ERK2 proteins depressed ChAT promoter activation by trapoxin
      in transient transfection assays. Conversely, the overexpression of
      constitutively active mutants of H-ras or MEK1 proteins had little or no effect
      on ChAT promoter activity, but strongly synergized with trapoxin. These data thus
      suggest that the activation of the MEK/ERK kinase cascade plays a necessary, but
      not sufficient, role in the regulation of ChAT promoter by inhibitors of histone
      deacetylase.

PMID- 9602090
TI  - Functional implications of the 21-24 loop in recombinant prochymosin.
AB  - To investigate the role of the 21-24 (pepsin numbering) loop in prochymosin, the
      amino acid residues GTPP at positions 21 through 24 were replaced with GG, the
      equivalent loop residues from its homologous protein, penicillopepsin, or SG, GS
      by site-directed mutagenesis. The mutants except GTPP(21-24)GS could be expressed
      in Escherichia coli. Activation studies indicated that the refolded prochymosin
      mutants were capable of undergoing autocatalytic activation to produce
      pseudochymosin by cleaving its N-terminal 27 amino acid residues at pH 2. The
      resulting pseudochymosin mutants were able to convert into chymosin at pH 5.5 by
      further autocatalytic cleavage to remove additional 15 amino acid residues. These
      results demonstrate that the prochymosin analogs can fold into an active state
      from an unfolded state and that the pseudochymosin analogs can proceed in the
      transformation from one active form into another active form. Spectroscopic
      analyses revealed that after mutation the far UV CD spectrum of prochymosin was
      considerably modified, showing less negative ellipticity values, and the
      fluorescence emission intensities of prochymosin and pseudochymosin were
      remarkably reduced. The stabilities of prochymosin and pseudochymosin,
      especially, were dramatically decreased. The stabilization energy of prochymosin
      was reduced by 7-8 kJ/mol. The inactivation temperature of pseudochymosin was
      decreased by 15-20 degrees C. The wild-type pseudochymosin was stable at pH 1.5
      and 6.5, whereas the mutants were completely inactivated at the same pH values.
      Taken together, it is reasonable to conclude that the 21-24 loop (GTPP) plays an
      important role in determining the stability of prochymosin and pseudochymosin,
      although the mutants with mutated loop (GG or SG) still can refold into an active
      conformation.

PMID- 9602091
TI  - Dynamic changes in glucocorticoid and mineralocorticoid receptor mRNA in the
      developing guinea pig brain.
AB  - The guinea pig has a high degree of neurological maturity at birth. Since
      glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) are central to
      several aspects of brain and neuroendocrine development, we examined the
      hypothesis that development of central GR and MR systems takes place during fetal
      life, in species which give birth to mature young. Fetal guinea pigs were
      retrieved on gestational days (gd) 40-45, 50-55, 60-65. A group of 7-day old
      neonates was also euthanized. Levels of GR and MR mRNA were determined by in situ
      hybridization followed by computerized image analysis. MR mRNA was confined to
      limbic structures, and was present at high levels in the hippocampus and dentate
      gyrus by gd40. Hippocampal MR mRNA levels decreased with the progression of
      gestation. GR mRNA was more widely distributed, with highest levels being
      expressed in the cingulate cortex, hippocampus, amygdala and hypothalamic
      paraventricular nucleus (PVN). In the hippocampus, GR mRNA levels increased with
      progression of gestation, attaining highest levels near term. In contrast to the
      hippocampus, GR mRNA levels were highest in the PVN at gd40-45, but decreased
      dramatically in the last 25 days of gestation. In conclusion, there are dynamic
      site-specific changes in the expression of corticosteroid receptors in the brain
      of the fetal guinea pig, at the time of most rapid brain growth. The decreases in
      GR mRNA levels in the PVN in late gestation likely facilitate the simultaneous
      increases in ACTH and cortisol that occur near term, and which are critical for
      the delivery of viable young.

PMID- 9602092
TI  - Amyloid precursor protein modulates the interaction of nerve growth factor with
      p75 receptor and potentiates its activation of trkA phosphorylation.
AB  - We have recently shown that the secreted form of amyloid precursor protein (APPs)
      potentiates the neurotrophic actions of nerve growth factor (NGF). The combined
      presence of NGF and APPs in low concentrations resulted in a synergistic
      potentiation of NGF neuritogenic activity on PC12 cells. Therefore, the effect of
      APPs on NGF receptor-binding has been examined. In the presence of APPs, the
      apparent affinity of NGF's low affinity binding site increased by a factor of
      2.5. In addition, a 2- to 2.5-fold decrease in the number of sites was observed,
      although APPs did not compete with NGF for the same binding sites. These effects
      of APPs were not caused by direct interaction with NGF itself. In addition, APPs
      synergistically potentiated the tyrosine phosphorylation of trkA due to NGF.
      These results suggest that an increased affinity of p75 for NGF may underlie the
      potentiation of neurotrophic actions of NGF by APPs, and that increase may be
      caused by an indirect interaction between APPs and p75.

PMID- 9602093
TI  - Effects of chronic systemic theophylline injections on recovery of
      hemidiaphragmatic function after cervical spinal cord injury in adult rats.
AB  - Based on a previous demonstration that acutely administered theophylline induces
      respiratory-related recovery in an animal model of spinal cord injury, the
      influence of chronically administered theophylline on maintaining recovery was
      assessed. The absence of respiratory-related activity in the left phrenic nerve
      and hemidiaphragm of rats subjected to an ipsilateral C2 spinal cord hemisection
      was confirmed electrophysiologically 24 h after injury. Theophylline was then
      injected i.p. for 3-30 consecutive days. Recovery of respiratory-related activity
      was observed in the majority (29 out of 32) of the experimental animals. We
      conclude that theophylline not only induces, but also maintains recovery for
      prolonged periods after cervical spinal cord injury.

PMID- 9602094
TI  - Inhibition of acetyl CoA carboxylase by GTP gamma S.
AB  - The effect of nonhydrolyzable guanine nucleotides on mammalian acetyl CoA
      carboxylase (ACC) activity was examined. Using porous rat adipocytes and crude
      fat cell homogenates to study metabolic pathway flux, GMPPNP and/or GTP gamma S
      inhibited [14C]fatty acid formation by up to 95% when either [6-14C]glucose-6
      phosphate or [1-14C]acetyl CoA was used as substrate. If [2-14C]malonyl CoA
      initiated flux, however, no inhibition was apparent. These pathway flux studies
      suggested that ACC was the locus of inhibition, and that the mechanism might
      involve a disruption of guanine nucleotide hydrolysis by the nonhydrolyzable
      analogues. Using partially and avidin-sepharose-purified ACC preparations from
      rat fat, liver and mammary tissue, citrate-stimulated ACC activity was inhibited
      by 25-75% with 50 microM GTP gamma S. Related compounds and nucleotides had
      absent-to-minimal effects on ACC. ATP gamma S was inhibitory (10-30% at 5-15
      microM), but always to a lesser degree than equimolar GTP gamma S. Filter binding
      assays with [alpha-32P]GTP or [35S]GTP gamma S were negative, but low-level
      GTPase activity was detected. Using photoaffinity labelling techniques, [alpha
      32P]GTP was found to bind ACC and not pyruvate carboxylase. The hypothesis that
      citrate-responsive ACC activity may be modulated by an intrinsic or associated
      GTP binding site is explored. Since ACC forms polymers, as does the cytoskeletal
      protein beta-tubulin, amino acid sequence comparisons between ACC and atypical
      GTP binding domain of beta tubulin are presented.

PMID- 9602095
TI  - Attention affects the organization of auditory input associated with the mismatch
      negativity system.
AB  - The mismatch negativity (MMN), a component of event-related potentials (ERP), was
      used to investigate the effect of attention on auditory stream segregation.
      Subjects were presented with sequences of alternating high and low tones that
      occurred at a constant rate, which they ignored. When subjects ignored the
      stimuli, the three-tone standard and deviant sequences contained within the high-
      and low-pitched tones did not emerge and no MMNs were obtained. Subjects were
      then instructed to attend to the high-pitched tones of the stimulus sequences and
      detect the within-stream deviants. When subjects selectively attended the high
      pitched tones, MMNs were obtained to the deviants within both the attended and
      unattended streams. These results indicate that attention can produce segregation
      such that the sequences of low- and high-pitched tones are available to the
      automatic deviance detection system that underlies the generation of the MMN.
      Selective attention can alter the organization of sensory input in the early
      stages of acoustic processing.

PMID- 9602096
TI  - The effects of central administration of neurotrophins or transplants of fetal
      tectal tissue on retinal ganglion cell survival following removal of the superior
      colliculus in neonatal rats.
AB  - In neonatal rats, intraocular injections of brain-derived neurotrophic factor
      (BDNF) or neurotrophin 4/5 (NT-4/5) enhance the survival of retinal ganglion
      cells (RGCs) following superior colliculus (SC) ablation [Q. Cui, A.R. Harvey, At
      least two mechanisms are involved in the death of retinal ganglion cells
      following target ablation in neonatal rats, J. Neurosci., 15, 1995, pp. 8143
      8155.]. The aim of the present study was to determine if: (i) fetal tectal tissue
      grafted into the lesion site, or (ii) neurotrophins applied centrally to the
      injured SC, also decreased lesion-induced RGC death. Nuclei of tectally
      projecting RGCs were identified by injecting diamidino yellow (DY) into the left
      SC of 2-day-old (P2) Wistar rats. Injected SCs were lesioned at P4. In some
      animals, embryonic (E16) tectal tissue was then implanted into the lesion cavity;
      host rats were perfused 24 h or 20 days later. In short-term (24-h) studies, the
      number of DY-labelled pyknotic profiles was compared to the number of normal DY
      labelled RGCs in retinal wholemounts (right eyes). The proportion of dying RGCs
      in animals with grafts (10.7%, n = 17) was not significantly different from
      lesion-only rats (13.2%, n = 26). Nonetheless, the long-term (20-day) study
      showed that, in most rats, fetal tectal tissue survived in the lesion cavity and
      in some cases, the grafts received host retinal input. In another group,
      different doses of BDNF or NT-4/5 were applied to the SC after P4 tectal lesions.
      Rats were perfused 24 h later and the number of pyknotic vs. normal DY-labelled
      RGCs was determined. Initial trials in which SC lesions were filled with gelfoam
      soaked in BDNF or NT-4/5 were unsuccessful; however, RGC death was reduced (p <
      0.05, Dunnett's test) in rats that received gelfoam implants as well as focal
      neurotrophin injections into SC rostral to the lesion. The lowest pyknotic rate
      in individual animals from the BDNF and NT-4/5 groups was 2.41% and 2.01%,
      respectively. Overall, the proportion of dying RGCs was 7.0% (n = 8) for BDNF and
      7.4% (n = 17) for NT-4/5 treated rats. Normal RGC densities were also
      significantly higher in these animals. NT-4/5 topically applied to the posterior
      surface of the eye did not reduce RGC death. The data show that the viability of
      injured neonatal RGCs is increased by specific retrograde neurotrophin-mediated
      survival signals which can be activated from the SC.

PMID- 9602097
TI  - Hippocampal Myc and p53 expression following transient global ischemia.
AB  - The proto-oncogene c-myc, and the tumor suppressor gene p53, encode proteins
      which function as transcriptional regulating factors governing cell
      proliferation, differentiation, and apoptosis. Recent evidence suggests that the
      delayed neuronal death which follows an episode of transient forebrain ischemia
      may involve apoptotic processes. We have therefore utilized immunohistochemistry
      to investigate the effects of transient global ischemia on neuronal expression of
      p53- and Myc-like immunoreactivities in the rodent forebrain 2, 12, 24, 48, and
      72 h following reperfusion. Transient global ischemia (20 min), produced by four
      vessel occlusion (4-VO), initially elevated p53-like immunoreactivity in both CA1
      and CA3 hippocampal subfields at 24 h of recirculation. However, distinct
      patterns of gene expression became evident in these regions at later time points.
      A pivotal difference was the persistence of ischemia-induced increases of p53-
      and Myc-like immunoreactivity in the CA1 region of the hippocampus. Unlike CA3
      neurons where p53-like immunoreactivity subsided to basal levels by 48 h of
      survival, CA1 neurons continued to display increased p53-immunoreactivity 48 h
      post-ischemia, while Myc-like immunoreactivity was selectively elevated in CA1
      neurons at this time point. Ischemia-induced increases in p53-like
      immunoreactivity were also detected in vulnerable regions of the amygdala,
      thalamus, and cortex 12 to 48 h after recirculation. Given that both p53 and Myc
      have been implicated in gene signalling pathways which mediate programmed cell
      death, our findings which demonstrate that 4-VO produces persistent elevations of
      p53- and Myc-like immunoreactivities in vulnerable neurons suggest that these
      proteins may also contribute to delayed neuronal death following an episode of
      transient forebrain ischemia.

PMID- 9602098
TI  - Chronic lead exposure accelerates decay of long-term potentiation in rat dentate
      gyrus in vivo.
AB  - Long-term potentiation (LTP) is a model of synaptic plasticity believed to
      encompass the underlying neurobiological mechanisms that support memory function.
      Chronic developmental lead (Pb) exposure is known to be associated with cognitive
      dysfunction in children and animals. Disruption of the induction of long-term
      potentiation (LTP) has been reported in the hippocampus following chronic
      exposure to environmentally relevant levels of Pb in rats. Under urethane
      anesthesia, we have previously observed Pb-induced increases in the threshold for
      LTP induction. With higher train intensities, LTP was induced and no declines in
      the amplitude of responses within a 60-min posttrain period were evident. The
      present study was designed to assess the effects of Pb on the more enduring forms
      of LTP in the dentate gyrus of the conscious rat. Beginning in the late
      gestational period, rats were chronically exposed to 0.2% Pb(2+)-acetate through
      the drinking water of the pregnant dam, and directly through their own water
      supply at weaning. As adults, electrodes were permanently implanted in male
      offspring and field potentials evoked by perforant path stimulation were recorded
      from the dentate gyrus over several weeks. LTP was induced by delivering theta
      burst patterned stimulation at a maximal stimulus intensity through the perforant
      path electrode, and input/output (I/O) functions were monitored for 1 month.
      Population spike (PS) amplitude was increased maximally 1 h after train delivery.
      The time constant of decay (tau) calculated from pooled data for each group
      yielded declines in PS amplitude by 63% in 17.4 days in controls and 13.4 days in
      Pb-exposed animals. Quantitative estimates of decay in individual animals were
      achieved in two ways: (1) by calculating difference scores in I/O functions from
      the maximal LTP at 1 h, and (2) by interpolating day to decay by 63% from
      declines from maximal LTP. The interpolated values were used to compare the
      incidence of animals showing decay of 63% within 1 week posttrain. Both analyses
      revealed a more accelerated rate of decay of LTP in animals developmentally
      exposed to Pb relative to controls. Endurance of potentiated responses for days
      to weeks is believed to be supported by structural modifications and synaptic
      growth. The reported effects of Pb on growth-related processes may thus
      contribute to a reduced persistence of LTP and the resulting cognitive deficits
      engendered by developmental Pb exposure.

PMID- 9602099
TI  - Reversible unfolding of sheep liver tetrameric serine hydroxymethyltransferase.
AB  - Equilibrium unfolding studies of the tetrameric serine hydroxymethyltransferase
      from sheep liver (SHMT, E.C.2.1.2.1) revealed that the holoenzyme, apoenzyme and
      the sodium borohydride-reduced holoenzyme had random coil structures in 8 M urea.
      In the presence of a non-ionic detergent, Brij-35, and polyethylene glycol, the 8
      M urea unfolded protein could be completely (> 95%) refolded by a 20-fold
      dilution. The refolded enzyme was completely active and kinetically similar to
      the native enzyme. The midpoint of inactivation of the enzyme occurred at a urea
      concentration that was much below the urea concentration required to bring about
      a substantial loss of secondary structure. This observation suggested the
      occurrence of a 'predenaturation transition' in the unfolding pathway. The
      equilibrium urea-induced denaturation curve of holoSHMT showed two transitions.
      The midpoint of the first transition was 1.2 M, which was comparable to that
      required for 50% decrease in enzyme activity. Further, 50% release of the
      pyridoxal-5'-phosphate (PLP) from the active site, as monitored by decrease in
      absorbance at 425 nm, also occurred at about 1.2 M urea. Size exclusion
      chromatography showed that the tetrameric SHMT unfolds via the intermediate
      formation of dimers. This dissociation occurred at a much lower urea
      concentration (0.15 M) in the unfolding of the apoenzyme, and at a higher urea
      concentration (1.2 M) in the unfolding of holoenzyme, thereby demonstrating the
      involvement of PLP in stabilizing the quaternary structure of the enzyme. Size
      exclusion chromatography of the refolding intermediates demonstrated that the
      cofactor shifts the equilibrium towards the formation of the active tetramer. The
      reduced holoenzyme could also be refolded to its native structure, as observed by
      fluorescence and CD measurements, indicating that the presence of covalently
      linked PLP does not affect refolding. The results demonstrate clearly that the
      dimer is an intermediate in the urea-induced equilibrium unfolding/refolding of
      sheep liver SHMT; and PLP, in addition to its role in catalysis, is required for
      the stabilization of the tetrameric structure of the enzyme.

PMID- 9602100
TI  - Developmental regulation and PKC dependence of Alzheimer's-type tau
      phosphorylations in cultured fetal rat hippocampal neurons.
AB  - Attempts to describe a mechanism of neurofibrillary tangle formation often focus
      on site specific phosphorylations of tau protein. These have typically been
      described in both Alzheimer's disease and developing brains. Therefore, study of
      the developmental regulation of Alzheimer epitope tau phosphorylations may help
      explain their persistence or recurrence during Alzheimer's disease. Using fetal
      rat hippocampal cultures, we report a spatial and temporal expression of tau
      phosphorylation during neuronal differentiation. We have examined phosphorylation
      at the epitopes recognized by monoclonal antibodies, PHF-1 and Tau 1. Tau was
      highly phosphorylated at the PHF-1 epitope at all culture ages examined using
      both immunohistochemical staining and Western blots. Tau was heavily
      phosphorylated at the Tau 1 epitope only in older cultures. The populations of
      tau recognized by the two antibodies also exhibited different solubilities,
      suggesting different microtubule binding behaviors: tau phosphorylated at PHF-1
      was retained in axons following solubilization whereas Tau 1 immunoreactive tau
      was not retained in any cell compartment. Finally, in this culture system,
      maintenance of phosphorylation at the PHF-1 epitope, but not the Tau 1 epitope,
      required protein kinase C activity. These results indicate unique regulatory
      mechanisms and roles for each of these phosphorylated tau epitopes.

PMID- 9602101
TI  - Ischemia-induced CA1 neuronal death is preceded by elevated FosB and Jun
      expression and reduced NGFI-A and JunB levels.
AB  - Alterations in levels of the immediate-early gene (IEG) proteins Fos, FosB,
      DeltaFosB, Jun, JunB, JunD, and NGFI-A were investigated in rat hippocampus by
      immunohistochemistry 2, 12, 24, and 48 h after forebrain ischemia. Transient
      global ischemia of 20 min, produced by four vessel occlusion (4-VO), elicited
      different patterns of IEG expression in vulnerable CA1 and more resilient CA3
      neurons. Cell counts revealed that except for JunD and NGFI-A, immunoreactivity
      for all examined IEGs was initially elevated by forebrain ischemia in both CA1
      and CA3 hippocampal subfields. However, distinct patterns of IEG expression
      became evident in these regions at later time points. The pivotal difference was
      the persistence of ischemia-induced elevations of FosB and Jun expression in the
      CA1 region of the hippocampus. Unlike CA3 neurons, where IEG immunoreactivity had
      subsided to basal levels by 24-48 h, CA1 neurons continued to display increased
      FosB- and Jun-like immunoreactivity 48 h post-ischemia. Western blot analysis
      revealed that elevated expression of both FosB and DeltaFosB-like proteins were
      responsible for the immunohistochemical detection of enhanced FosB-like
      immunoreactivity in CA1 neurons at 48 h. These findings are consistent with
      recent in vitro studies that implicate FosB and Jun in gene signalling pathways
      responsible for programmed cell death. In contrast to FosB and Jun, JunB
      expression declined significantly below basal levels in CA1 neurons at 48 h, yet
      remained unaltered in CA3 neurons. Given that JunB can inhibit the
      transactivating properties of Jun, decreased JunB levels may contribute to the
      apoptotic death of CA1 neurons by enhancing the transcriptional regulating
      activity of Jun. Also notable at 48 h was the complete loss of constitutive NGFI
      A expression from CA1 neurons of ischemic animals. These findings suggest that
      persistent elevations in FosB and Jun expression, concurrent with reductions in
      JunB and NGFI-A levels, contribute to the apoptotic death of CA1 neurons after
      forebrain ischemia.

PMID- 9602103
TI  - Veratridine-treated brain slices: a cellular model for epileptiform activity.
AB  - This study introduces veratridine-treated brain slices as a new in vitro synaptic
      independent model for epileptiform discharge. Studies were performed on the
      hippocampus in rat brain slices using conventional electrophysiological
      intracellular recording techniques. Veratridine (0.3 microM) produced a time
      dependent blockade of synaptic transmission as indicated by inhibition of the
      evoked population spike in the region CA1 of the hippocampus. However, in the
      same slices, intracellularly-evoked single action potentials were converted to
      epileptiform bursting shortly after exposure to veratridine. Additionally, in the
      veratridine model, spontaneous epileptiform activity developed after prolonged
      (more than 45 min) superfusion. The model was utilized to examine the action of
      two antiepileptic drugs: a sodium channel dependent and a synaptic dependent
      antiepileptic agents. Therapeutic concentrations of valproic acid (VPA, 10-100
      microM) inhibited both evoked and spontaneous bursting induced by veratridine.
      However, therapeutic concentrations of the synaptic-dependent antiepileptic drug
      phenobarbital (20-40 microM) failed to inhibit veratridine-induced bursting.
      These results demonstrate that the veratridine-treated brain slice is a simple
      and reliable model for studying mechanisms of action and for screening of
      potential sodium channel-dependent antiepileptic drugs.

PMID- 9602104
TI  - Interaction of cisplatin with human serum albumin. Drug binding mode and protein
      secondary structure.
AB  - Cis-diamminedichloroplatinum(II) (cisplatin) is an antitumor drug, which forms
      intrastrand cross-links DNA adducts. Protein interaction with cisplatin-DNA
      complexes induces DNA bending and biopolymer structural changes. This study is
      designed to examined the interaction of cisplatin with human serum albumin (HSA)
      in aqueous solution at physiological pH with drug concentrations of 0.0001 mM to
      0.1 mM, and HSA (fatty acid free) concentration of 2% w/v. Absorption spectra and
      Fourier transform infrared (FTIR) spectroscopy with its self-deconvolution and
      second derivative resolution enhancement, as well as curve-fitting procedures,
      were used to determine the drug binding mode, drug binding constant and the
      protein secondary structure in aqueous solution. Spectroscopic evidence showed
      that at low drug concentration (0.0001 mM), minor cisplatin-protein interaction
      occurs, while at higher drug content (0.001 mM), major Pt-HSA complexation takes
      place via protein C=O, C-N and S-H donor groups with overall binding constant K =
      8.52 x 10(2) M-1. At high drug concentration, cisplatin binding results in major
      protein secondary structural changes from that of the alpha-helix 55% (free HSA)
      to 45% and beta-sheet 22% (free HSA) to 32%, in the cisplatin-HSA complexes. The
      observed spectral changes indicate a partial unfolding of the protein structure,
      in the presence of cisplatin at high drug concentrations.

PMID- 9602105
TI  - Abdominal vagotomy attenuates interleukin-1 beta-induced nitric oxide release in
      the paraventricular nucleus region in conscious rats.
AB  - Nitric oxide (NO) has recently been shown to modulate the hypothalamic-pituitary
      adrenal axis response to interleukin-1 beta (IL-1 beta). We measured levels of
      nitrite (NO2-) and nitrate (NO3-) in the hypothalamic paraventricular nucleus
      (PVN) region using an in vivo brain microdialysis technique in conscious rats.
      Intraperitoneally administered IL-1 beta produced a significant increase in both
      NO2- and NO3- levels in the PVN region. We also examined the possible involvement
      of the abdominal vagal afferent nerves in this effect. In abdominal-vagotomized
      rats, the increase was significantly attenuated compared to that in sham-operated
      rats. Our results suggest that the abdominal vagal afferent nerves are involved
      in intraperitoneally administered IL-1 beta-induced NO release in the PVN region.

PMID- 9602106
TI  - Quantified distribution of serotonin transporter and receptors during the
      postnatal development of the rat barrel field cortex.
AB  - Serotonin membrane transporter and 5-HT1B and 5-HT2A receptors were visualized
      and measured by autoradiography in the rat barrel field cortex at postnatal days
      4, 8, 12, 16 and in adult (> P60). [3H]citalopram binding, reflecting the
      presence of 5-HT transporter on thalamocortical fibers, produced a clearcut
      barrel pattern from P4 to P16 (peak at P8), and decreased to a dispersed, low
      density in the adult. The patterning and temporal profile of 5-HT1B receptor
      binding ([125I]cyanopindolol) followed a parallel course. The 5-HT2A receptor
      binding ([125I]DOI) also conformed transiently to a barrel pattern; it increased
      in density from P8 to P16 and returned to a level as low as at P4 in the adult.
      These data suggest that 5-HT exerts a dual role in the developing somatosensory
      cortex: a local regulation of the peripherally-induced activity of
      thalamocortical axons via 5-HT1B receptors, and a trophic-like influence mediated
      by 5-HT2A receptors and possibly involving BDNF.

PMID- 9602107
TI  - Magnetic studies of the trinuclear center in laccase and ascorbate oxidase
      approached by EPR spectroscopy and magnetic susceptibility measurements.
AB  - The trinuclear centers in Rhus vernicifera laccase and Cucumis sativus ascorbate
      oxidase have been studied by EPR spectroscopy and magnetic susceptibility
      measurements over the wide range of 5 K to 300 K. The EPR spectra showed that
      type II copper receives increasing tetrahedral distortion with raising
      temperature. Magnetic susceptibilities of laccase showed that both of type I and
      type II coppers are almost fully paramagnetic since the antiferromagnetic
      interaction between type III coppers is extremely strong from 5 K to 300 K. On
      the other hand, the effective magnetic moment of ascorbate oxidase is contributed
      by ca. 1.7 Cu2+ even below ca. 100 K, since type II Cu is partly in the reduced
      form. The effective magnetic moment continuously increased with raising
      temperature because the antiferromagnetic interaction between type III coppers is
      not as strong as in the case of laccase. The simulation of the SQUID measurement
      results suggested that the conformational change of the ascorbate oxidase
      molecule caused the temperature dependence of the antiferromagnetic interaction.
      The type II Cu EPR signals in laccase and ascorbate oxidase were conspicuously
      broadened with raising temperature because of the increasing contribution of the
      triplet state by type III Cu's and/or of the rapid relaxation which finally led
      to only ca. 30% detection of the type II Cu signals at room temperature. The
      stepwise binding of azide to the trinuclear center made one of type III Cu's to
      be EPR detectable. SQUID measurements indicated that only one Cu in the
      trinuclear center is paramagnetic and other two Cu's are antiferromagnetically
      coupled for both of the one- and two-azide bound forms. The binding mode of azide
      to the trinuclear center was discussed based on some models.

PMID- 9602108
TI  - Arachidonic acid-sensitive A-currents and multiple Kv4 transcripts are expressed
      in chick ciliary ganglion neurons.
AB  - A-currents (IA) of chick ciliary ganglion (CG) neurons were blocked reversibly by
      arachidonic acid and a non-metabolizable analog of arachidonic acid, 5,8,11,14
      eicosatetraynoic acid. Inhibition of IA by both lipids was observed in whole-cell
      recordings and in excised inside-out patches, suggesting that Kv4 (Shal) subunits
      contribute to functional IA channels in CG neurons. Consistent with this, Kv4.2
      and Kv4.3 cDNAs were isolated by RT-PCR from chick CG neurons.

PMID- 9602109
TI  - Specific reductions of striatal prodynorphin and D1 dopamine receptor messenger
      RNAs during cocaine abstinence.
AB  - It is well established that the opioid neuropeptide and dopamine systems are
      altered following the use of cocaine. However very little information is
      available about their possible involvement during cocaine abstinence. In the
      present study, the mRNA expression of the dopamine receptors, D1 and D2, and the
      opioid peptides, prodynorphin and proenkephalin, were analyzed in the rat
      striatum using in situ hybridization histochemistry. Saline or cocaine (30 mg/kg,
      i.p.) were administered to rats once daily for 1 or 10 days. To examine cocaine
      abstinence, animals were treated for 10 days as described followed by a 10-day
      drug free period. Acute and intermittent cocaine administration elevated the
      prodynorphin mRNA expression in the dorsal striatum, consistent with previous
      reports, while the abstinent phase resulted in a significant reduction of
      prodynorphin mRNA levels in the ventrorostral striatum. The D1-receptor mRNA was
      decreased in the caudorostral striatum during cocaine withdrawal, a finding
      opposite to the increase observed following a single injection of the drug.
      Proenkephalin and the D2-receptor mRNAs were not altered during cocaine
      abstinence, though proenkephalin was elevated following acute but not repeated
      cocaine administration. These results show long-term suppression on prodynorphin
      and D1-receptor systems in specific striatal populations localized mainly in
      rostral areas during withdrawal from cocaine.

PMID- 9602110
TI  - Morphological consequences of altered calcium-dependent transmembrane signaling
      on the development of cultured cerebellar Purkinje neurons.
AB  - Morphometric analyses of cultured rat Purkinje neurons, visualized with anti
      calbindin, demonstrated that elevated KCl (10 mM) significantly increased
      dendritic outgrowth and branching. The response was blocked by NiCl2 (50 microM;
      R-type Ca2+ channel antagonist). Cells grown in low external Ca2+ (100 nM) showed
      no loss of responsiveness to elevated potassium. However, thapsigargin (1 microM;
      Ca(2+)-ATPase blocker) inhibited dendrite outgrowth, suggesting that
      intracellular calcium stores may be important in governing development.

PMID- 9602111
TI  - Cholinergic structures and neuropathologic alterations in the olfactory bulb of
      Alzheimer's disease brain samples.
AB  - This report describes the laminar distribution of acetylcholinesterase-positive
      structures and the neuropathologic alterations in the human olfactory bulb of
      control and Alzheimer's disease brain samples. The results suggests that no
      correlation exists between the distribution of cholinergic axons and the
      neuropathological alterations in the different layers in Alzheimer's disease.

PMID- 9602112
TI  - Increased expression of amyloid precursor protein and amyloid precursor-like
      protein 2 during trophic factor withdrawal-induced death of neuronal PC12 cells.
AB  - Programmed cell death (PCD) (apoptosis) is implicated in the neuronal cell death
      of Alzheimer's disease (AD). We investigated expression of amyloid precursor
      protein (APP) and amyloid precursor-like protein 2 (APLP2) during trophic factor
      deprivation-induced PCD of neuronally differentiated PC12 cells. Neuronal PC12
      cells underwent PCD within two days following withdrawal of nerve growth factor
      (NGF) from the culture medium. Total APP mRNA levels increased gradually after 24
      h, reaching levels 250% higher than those in control cells at 48 h after NGF
      withdrawal, and total APLP2 mRNA levels also increased similarly at 48 h.
      Analysis of the three major APP mRNA isoforms APP695, APP751, and APP770 by
      reverse transcription polymerase chain reaction showed a substantial increase in
      the proportion of APP770 at 48 h after NGF withdrawal. Basic fibroblast growth
      factor, which prevented the appearance of PCD after NGF withdrawal, inhibited the
      increases in APP and APLP2 mRNA levels as well as the increase in the proportion
      of APP770. Cellular holoprotein levels of total APP, APP containing the Kunitz
      protease inhibitor domain, and APLP2 also increased by approximately 60%, 100%,
      and 30%, respectively, at 48 h after NGF withdrawal. These data indicate that in
      neuronal PC12 cells undergoing PCD following trophic factor withdrawal, the
      syntheses of both APP and APLP2 are upregulated, and the alternative splicing of
      the APP gene is modified. This implies a linkage between APP and APLP2 expression
      and neuronal PCD.

PMID- 9602113
TI  - Role of metal-ligand coordination in the folding pathway of zinc finger peptides.
AB  - In the zinc fingers of TFIIIA family, two cysteines near the N-terminus and two
      histidines near the C-terminus are conserved for each finger unit. A cooperative
      binding of these residues to a Zn(II) ion is essential for the formation of the
      finger structure consisting of an anti-parallel beta-sheet and an alpha-helix. In
      order to reveal the folding pathway of the zinc finger, we have investigated, by
      Raman spectroscopy, the relationship between Zn(II)-ligand binding and
      conformational change of a 27-mer peptide representing the third finger of mouse
      transcription factor Zif268. In the absence of Zn(II), the peptide assumes a beta
      sheet-rich structure. Upon addition of Zn(II), cysteines preferentially bind to
      Zn(II) prior to the metal coordination of histidines. Both the Zn(II)-cysteine
      and Zn(II)-histidine binding induce a partial secondary structure transition from
      beta-sheet to alpha-helix. Exchange of the ligand amino acid residues, i.e.,
      cysteines to histidines and vice versa, produces a striking effect on the folding
      of the peptide. The beta-sheet-->alpha-helix transition is induced only by the
      Zn(II)-cysteine binding and the ligand exchanged peptide is not capable of
      folding into the finger structure. The present results demonstrate the importance
      of the ligand arrangement in the folding of zinc finger.

PMID- 9602114
TI  - Naloxone does not alter amphetamine-induced rotational behavior or striatal
      dopamine levels of nigrally-lesioned rats.
AB  - Previous studies on rats have shown that the opioid antagonist naloxone
      attenuates amphetamine-induced stimulation of locomotor activity and increases in
      extracellular dopamine in the brain. However, in this study, naloxone did not
      attenuate amphetamine-induced rotational behavior or increases of extracellular
      dopamine in the intact striatum of nigrally-lesioned rats. These results suggests
      differences in the way in which endogenous opioids contribute to the behavioral
      and neurochemical effects of amphetamine in nigrally-lesioned compared to intact
      rats.

PMID- 9602116
TI  - Structural determination of lipid-bound human blood coagulation factor IX.
AB  - Human coagulation factor IX (FIX) is a serine protease which binds to a
      negatively charged phospholipid surface in the presence of Ca ions (Ca2+). FIX
      two-dimensional (2-D) crystals were obtained by the lipid layer crystallisation
      technique under near physiological conditions. The 2-D projection map of the
      protein was calculated to a resolution of 3 nm using electron crystallographic
      analysis. The structural organisation of membrane-bound FIX is discussed and
      compared with the known X-ray crystallographic data.

PMID- 9602115
TI  - Nitric oxide-mediated cGMP production in the islands of Calleja in the rat.
AB  - cGMP-immunostaining in the islands of Calleja (ICj) in slices incubated in vitro
      partially co-localized with nitric oxide synthase (NOS) inside the ICj. No cGMP
      immunostaining was found outside the ICj in unstimulated slices, whereas the NO
      donor sodium nitroprusside (SNP) stimulated cGMP in cells and fibers bordering on
      the ICj. These findings show an ongoing NO synthesis in in vitro slices and
      suggest a relatively restricted diffusion range for endogenously synthesized NO.

PMID- 9602117
TI  - Amyloid-beta-protein isoforms in brain of subjects with PS1-linked, beta APP
      linked and sporadic Alzheimer disease.
AB  - To determine whether similar abnormalities of various soluble full-length and N
      terminal truncated Abeta peptides occur in postmortem cerebral cortex of affected
      PS1 mutation carriers, we examined the amounts of two amyloid species ending at
      residue 40 or at residues 42(43) using sandwich ELISA systems. Our results
      indicate that PS1 mutations effect a dramatic accumulation in brain of the highly
      insoluble potentially neurotoxic long-tailed isoforms of the Abeta peptide such
      as Abeta1-42(43) and Abetax-42(43). This enhancing effect of PS1 mutation on
      Abetax-42(43) deposition was highly similar to that of a betaAPP mutation
      (Val717Ile) but the effects on Abetax-40 production were significantly different
      between these two causal genes. In contrast to previous studies of soluble Abeta
      in plasma and in supernatants from cultured fibroblasts of subjects with PS1
      mutations, our studies also show that there is an increase in insoluble Abetax-40
      peptides in brain of subjects with PS1 mutations.

PMID- 9602118
TI  - Nucleotide sequence and deduced amino acid sequence of a putative asparagine
      synthetase in the mosquito Aedes aegypti (L.).
AB  - A cDNA was cloned from a Aedes aegypti head cDNA library, containing the complete
      coding sequence for an asparagine synthetase homolog. The predicted polypeptide
      sequence exhibits high homology with different proteins of the 'purF' glutamine
      amidotransferase enzyme family. The aminoterminal region, containing Cys-1 which
      is crucial to perform the glutaminase reaction, was highly conserved among the
      asparagine synthetase family. Subsequent expression of the cDNA yielded a 54,000
      Da protein corresponding to the molecular weight of other asparagine synthetases.

PMID- 9602119
TI  - Isothermal titration calorimetric studies on the associations of putidaredoxin to
      NADH-putidaredoxin reductase and P450cam.
AB  - Putidaredoxin (Pdx), an iron-sulfur protein containing a 2Fe-2S cluster, serves
      as a physiological electron mediator from NADH-putidaredoxin reductase (PdR) to
      P450cam in the P450cam monooxygenation reaction cycle. Previous studies have
      revealed that the associations of Pdx with P450cam and PdR are not strongly
      dominated by electrostatic interactions, although such interactions stabilize
      most electron-transfer complexes [A.R. De Pascalis, I. Jelesarov, F. Ackermann,
      W.H. Koppenol, M. Hiroasawa, D.B. Knaff, H.R. Bosshard, Protein Sci. 2 (1993)
      1126-1135]. In the present study, to elucidate the interactions dominating the
      specific associations in the electron-transfer reaction mediated by Pdx, the
      thermodynamic properties--entropy (delta S), enthalpy (delta H), and heat
      capacity changes (delta Cp)--for PdR/Pdx and P450cam/Pdx association reactions
      have been examined by isothermal titration calorimetry (ITC). Although the
      binding enthalpy change, delta Hbind, for the PdR/Pdx association is positive at
      10 degrees C, it declines linearly with temperature in the range 10-22 degrees C
      and becomes negative above 11 degrees C. On the other hand, the binding entropy
      change, delta Sbind, is positive at all temperatures examined in this study,
      indicating that the association of Pdx to PdR is entropically driven. On the
      basis of the temperature dependence of delta Hbind, delta Cpbind for the
      association of Pdx to PdR was estimated as -1.24 kJ mol-1 K-1. This value is
      larger than those reported for other electron-transfer protein systems (e.g., 
      0.68 kJ mol-1 K-1 for ferredoxin/ferredoxin: NADP+ reductase), suggesting that
      the PdR/Pdx association may be dominated by hydrophobic rather than electrostatic
      components. For the P450cam/Pdx association, the negative delta Sbind and highly
      favorable delta Hbind were observed, behavior that stands in sharp contrast to
      the association reactions in other electron-transfer proteins. The energetics of
      the P450cam/Pdx association are similar to those of binding reaction of antibody
      to antigen in which van der Waals and hydrogen bonding interactions are dominant,
      resulting in high specificity in the association of Pdx with P450cam.

PMID- 9602120
TI  - A P-type ATPase from the aquatic fungus Blastocladiella emersonii similar to
      animal Na,K-ATPases.
AB  - We have cloned a P-type ATPase gene from the aquatic fungus Blastocladiella
      emersonii (BePAT1) using a probe obtained with degenerate oligonucleotides,
      corresponding to two amino acid sequences highly conserved among all P-type
      ATPase isoforms, and the polymerase chain reaction technique. Nucleotide sequence
      analysis revealed a 3.4 kb open reading frame encoding a putative peptide of 1080
      amino acid residues with a calculated molecular mass of 119 kDa, which presents
      all diagnostic features of P-type transporting ATPases. Comparison to other
      members of the family and phylogenetic analyses have shown that the BePAT1
      protein belongs to the subfamily of Na,K- and H,K-ATPases, indicating that the
      divergence between the alpha-subunit of the Na,K-ATPase and other members of the
      P-type ATPase family has occurred before the divergence between the animal and
      fungal lineages in evolution.

PMID- 9602121
TI  - Nuclear factor-kappa B activation during cerebral reperfusion: effect of
      attenuation with N-acetylcysteine treatment.
AB  - We examined activation of the transcription factor, nuclear factor-kappaB (NF
      kappaB), which participates in the upregulation of endothelial cell adhesion
      proteins, during reperfusion after temporary middle cerebral artery occlusion
      (TMCAO). We hypothesized that N-acetylcysteine (NAC), an antioxidant which
      inhibits NF-kappaB activation, would alter events in brain reperfusion injury. We
      used a rat model of TMCAO. The left sides of the brains were rendered ischemic
      for 2 h, and then the area was allowed to reperfuse. The animals were treated
      with NAC (150 mg/kg) or saline placebo, sacrificed, and activated NF-kappaB was
      assessed in both the left and right hemispheres, all at varying intervals.
      Cerebral infarction volume was also measured in each of the hemispheres collected
      from a separate group of animals. Activated NF-kappaB, consisting of p65 and p50
      Rel proteins, was significantly increased 15 min after reperfusion in the
      affected hemisphere. The activation at 15 min was completely abolished with NAC
      treatment. NAC treatment 1 h prior to the end of occlusion and at 24 h reduced
      the percentage infarction volume of the affected hemispheres from 35.5+/-2.8%
      (S.E.) to 18. 1+/-2.1% (p<0.01). NAC treatment at 1 h after the occlusion (after
      the NF-kappaB peak) and again at 24 h also significantly reduced the percentage
      infarction volume from 34.8+/-3.8% to 24.6+/-3.8% (p<0. 05). Thus, while NAC
      inhibited activation of NF-kappaB at 15 min after reperfusion, the drug acted to
      reduce cerebral infarction by additional, undefined mechanisms. These results
      bring into question the various roles of NF-kappaB in cerebral infarction
      followed by reperfusion.

PMID- 9602122
TI  - Molecular cloning and characterization of a rabbit eIF2C protein.
AB  - Rabbit eIF2C (94kDa) has been shown to play important roles in the eukaryotic
      peptide chain initiation process. In this study, the primary structure of rabbit
      eIF2C is determined by cDNA cloning. Based on the partial amino acid sequences of
      Endolys C cleaved fragments, degenerate oligonucleotides were synthesized and
      used as primers for the polymerase chain reaction to amplify the corresponding
      cDNA fragment from a rabbit liver cDNA library. This fragment was subsequently
      used to screen for larger cDNAs. Marathon cDNA amplification and 5'-rapid
      amplification of cDNA ends were used to confirm the translation start site.
      Sequences from the overlapping clones were assembled into a 3599-bp composite
      sequence, which contains a single open reading frame that translates into a 813
      deduced amino acid sequence. Northern blot analysis of rabbit liver ploy(A)+ RNA
      yielded a single message species at approximately 4.6kb. Western blot analysis of
      rabbit reticulocyte lysate using polyclonal antibody against the 94kDa eIF2C
      detected a higher-molecular-weight polypeptide (140kDa). No 94kDa polypeptide was
      detected. The cloned cDNA was further characterized by in-vitro transcription
      coupled translation in reticulocyte lysate. The translated product was
      precipitated with antibodies against eIF2C. Genomic Southern blot analysis
      indicates that the rabbit eIF2C is a single copy gene. Sequence analysis reveals
      that rabbit eIF2C has strong homology with a hypothetical protein in
      Caenorhabditis elegans.

PMID- 9602123
TI  - Biochemical characterization of the pectate lyase PelZ of Erwinia chrysanthemi
      3937.
AB  - To degrade the plant pectin, the phytopathogenic bacterium Erwinia chrysanthemi
      produces a set of at least seven endo-pectate lyases (Pels). Five major (PelA,
      PelB, PelC, PelD and PelE) and two minor isoenzymes (PelL and PelZ) have been
      identified. PelZ is an extracellular enzyme secreted by the Out system. According
      to its amino acid sequence, the PelZ protein belongs to a new family. The PelZ
      protein was overproduced in E. coli and purified to compare its enzymatic
      properties to that of the other Pels of E. chrysanthemi. PelZ exhibits a low
      specific activity but good affinity for the substrates including partially
      methylated pectins (up to 45% methylation). The main characteristic of PelZ is
      the requirement for both Ca2+ and Mn2+ as cofactors while the other Pels require
      only Ca2+. The cooperative effect of these two cations suggests the presence of
      distinct binding sites. The PelZ activity is sensitive to inhibition by excess of
      substrate, by oligogalacturonides, by the ionic strength and by different plant
      compounds. PelZ was shown to act in synergy with the major isoenzyme PelE, while
      competition was observed between PelZ and the minor pectate lyase PelL. No
      synergistic action was observed between PelZ and PelA, PelB, PelC or PelD.

PMID- 9602124
TI  - The cell cycle gene SKP1 is regulated by light in postnatal rat brain.
AB  - During the early postnatal phase of high neuronal plasticity, an altered visual
      input leads to great modifications of visual cortex organization [Y. Fregnac, M.
      Imbert, Development of neuronal selectivity in primary visual cortex of cat,
      Physiol. Rev., 64 (1984) 375-434; D.H. Hubel, T.N. Wiesel, S. LeVay, Plasticity
      of ocular dominance columns in monkey striate cortex, Philos. Trans. R. Soc.
      London, Ser. B, 278 (1977) 377-409.]. We used refined differential screening of
      an organized cDNA library to identify the genes that may participate in this
      plasticity. We isolated a candidate plasticity gene encoding for a 163 aa protein
      that is closely related to the human and yeast Skp1p, a key factor in cell cycle
      progression [C. Bai, K. Hofman, L. Ma, M. Goebl, J.W. Harper, S.J. Elledge, SKP1
      connects cell cycle regulators to the ubiquitin proteolysis machinery through a
      novel motif, the F-box, Cell, 86 (1996) 263-274; C. Connelly, P. Hieter, Budding
      yeast SKP1 encodes an evolutionary conserved kinetochore protein required for
      cell cycle progression, Cell, 86 (1996) 275-285; H. Zhang, R. Kobayashi, K.
      Galaktionov, D. Beach, p19Skp1 and p45Skp2 are essential elements of the cyclin A
      CDK2 S phase kinase, Cell, 82 (1995) 915-925.]. Northern blot analysis showed
      that the expression of SKP1 (Skp1p gene) dramatically decreased after 2 h of
      light stimulation in the visual cortex of young dark-reared rats. This down
      regulation lasted at least 72 h. It was specific for the critical period as we
      did not observe any significant regulation of SKP1 mRNA by light in adult dark
      reared rat brain. The down regulation was observed in the superior colliculus but
      also in the frontal cortex and in the hippocampus. The fact that this down
      regulation was not restricted to the visual system, suggested that it could be
      produced by dark rearing-induced hormonal changes. The significance of SKP1
      expression in the brain and its regulation are discussed.

PMID- 9602125
TI  - Structure of the Drosophila DNA topoisomerase I gene and expression of messages
      with different lengths in the 3' untranslated region.
AB  - The nucleotide sequence of the Drosophila DNA topoisomerase I gene (top1) has
      been determined. Structurally, top1 consists of eight exons and seven introns.
      The top1 coding region contains a new class of opa repeats, encoding clusters of
      serine residues instead of glutamine repeats usually seen in Drosophila genes of
      the neurogenic loci. A unique feature of top1 is the developmental switch of its
      transcripts: a heterogeneous population of transcripts ranging from 3.8 to 4.2kb
      seen maximally at 0-2h of embryogenesis and a 5.2-kb transcript maximal at 6-12h
      of embryonic development. The transcripts expressed in the 0-2-h embryo have been
      shown as maternal storage products specific to ovarian tissues. RACE analysis
      shows that whereas the 6-12-h transcripts have a single site for polyadenylation,
      there are at least 12 different sites for poly(A) addition to the 0-2-h
      transcripts. An additional intron specific for the maternal storage transcripts
      appears in some of the 0-2-h transcripts. No significant heterogeneity at the 5'
      end of the top1 transcripts is seen. Sequence searches have revealed a number of
      regulatory sequences for potential translational control in the 3' untranslated
      region.

PMID- 9602126
TI  - Binding of monovalent anions to human serum transferrin.
AB  - Serum transferrin is the protein whose primary function is to bind iron and
      transport it through the blood. Apotransferrin has two specific metal-binding
      sites that bind a variety of metal ions in addition to the ferric ion. The
      distinguishing feature of the transferrins is that a "synergistic" bicarbonate
      anion is bound along with the metal ion to form a stable Fe(3+)-CO3-Tf ternary
      complex. Previous research has shown that apotransferrin will also bind divalent
      anions such as phosphate and sulfate. Difference UV spectroscopy has now been
      used to show that a series of monovalent anions bind weakly to apotransferrin.
      Equilibrium constants for the binding of chloride, perchlorate, bromide, fluoride
      and Hepes have been calculated. A reaction scheme for the binding of anions is
      proposed which predicts that the binding of the nonsynergistic anions to
      apotransferrin will interfere with metal binding by competing directly with the
      binding of the synergistic bicarbonate anion. Difference UV data are presented
      which demonstrate this type of competition between nonsynergistic anions and
      Tb3+. Competition from the nonsynergistic anions follows the order HPO4(2-) >
      SO4(2-) approximately F- > ClO4- approximately Cl- approximately Br-. Speciation
      calculations have been performed to determine the concentrations of anion
      apotransferrin complexes in Hepes and Tris buffers and in human serum and to
      estimate the extent to which competition from anions in the buffer will interfere
      with metal-binding to apotransferrin.

PMID- 9602127
TI  - Increased expression of voltage-activated calcium channels in cultured
      hippocampal neurons from mouse trisomy 16, a model for Down syndrome.
AB  - Calcium is an important second messenger that affects metabolic and physiological
      activities of developing and mature neurons. It has been reported that electrical
      activity is abnormal in cultured hippocampal and DRG neurons from the trisomy 16
      (Ts16) mouse, a model for Down syndrome (trisomy 21-Ts21 in human). Whole-cell
      voltage-clamp, radiolabeled ligand binding techniques and mRNA measurements were
      used to study the effect of Ts16 on voltage-dependent calcium currents in
      cultured fetal hippocampal neurons from the Ts16 mouse. In neither Ts16 nor
      control diploid neurons were low-voltage-activated calcium currents detected.
      However, a high-voltage-activated (HVA) calcium current was identified and shown
      to be dihydropyridine sensitive. The density of this HVA calcium current was 80%
      greater in Ts16 neurons than in control. This difference correlated with a 70%
      increase in binding of radiolabeled dihydropyridine, PN200-110, a marker of L
      type calcium channels. However, mRNA levels encoding the alpha1C and alpha1D
      subunits were unchanged in the Ts16 neurons. In contrast, mRNA level of the myo
      inositol transporter, the gene for which is located on mouse chromosome 16, was
      elevated in Ts16 neurons due to a gene-dosage effect. Therefore, it is likely
      that posttranscriptional regulation of dihydropyridine-sensitive voltage
      dependent calcium channels is abnormal in Ts16. As dihydropyridine sensitive HVA
      Ca channels are implicated in heterosynaptic long-term depression and long-term
      potentiation, the differences reported here, if also present in the Down syndrome
      brain, may contribute to mental retardation in that disorder.

PMID- 9602128
TI  - Molecular cloning, structural organization, sequence, chromosomal assignment, and
      expression of the mouse alpha-N-acetylgalactosaminidase gene.
AB  - Alpha-N-acetylgalactosaminidase (2-acetamido-2-deoxy-alpha-d-galactoside
      acetamidodeoxy-galactohydrolase, NAGA; EC 3.2.1.49) deficiency is a recently
      recognized autosomal recessive lysosomal disease. As a prerequisite for the
      generation of an animal model, the mouse NAGA gene was cloned and characterized.
      The NAGA gene was assigned to mouse chromosome 15 band E3, syntenic to the region
      encompassing the human gene, and NAGA-deficient mutant human cells transfected
      with the cosmid clone containing the mouse NAGA gene expressed NAGA activity.
      Comparison of the mouse NAGA nucleotide sequence with the human NAGA sequence
      predicted that the mouse NAGA gene contains an open reading frame of 1245bp,
      comprising nine coding exons and spanning a genomic region of 8258bp, and a 3'
      untranslated region of 0.5kb. The 5' untranslated region was determined in primer
      extension studies to be 235bp in length. Nucleotide identity between the human
      and mouse NAGA exons ranged from 67.4 to 89.5%, with better matches for exons 1-7
      than for 8 and 9. The overall amino acid identity between the mouse and human
      deduced NAGA polypeptides was 82.0%, between those of mouse and chicken 72.9%.
      Homology was found to only one other mouse gene, i.e. the alpha-galactosidase A
      (GALA; EC 3.2.1. 22) gene. The amino acid identity ranged from 51.6 to 62.1% in
      the polypeptide regions corresponding to NAGA exons 2-7 and GALA exons 1-6, but
      little, if any, in the remainder. These analyses gave emphasis to the strong
      conservation of the NAGA gene and its origin from an ancestor common with the
      GALA gene, with NAGA exons 8 and 9 and GALA exon 7 being the most divergent
      regions in the evolution of the two genes.

PMID- 9602129
TI  - Expression of the human excitatory amino acid transporter 2 and metabotropic
      glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and
      patients with schizophrenia.
AB  - A disturbance of glutamatergic transmission has been suggested to contribute to
      the development of schizophrenic pathophysiology based primarily on the ability
      of glutamate receptor antagonists to induce schizophrenic-like symptoms, and
      recent studies suggesting reduced glutamatergic function in the prefrontal cortex
      (PFC) of individuals with a diagnosis of schizophrenia. In order to investigate
      this hypothesis further, the expression of several 'glutamatergic' markers, the
      metabotropic glutamate receptors (mGluRs; mGluR3, 5) and the human excitatory
      amino acid transporter (EAAT2) were compared in the PFC of normal individuals and
      schizophrenics. The present results showed that glial cells in the pyramidal
      layers of the PFC from schizophrenics had decreased EAAT2 mRNA content relative
      to controls in Brodmann areas 9 and 10. The cellular levels of expression of the
      two mGluR signals investigated (mGluR3, and 5) were not significantly changed
      relative to controls except for an increase in the neuronal mGluR5 in the
      pyramidal cell layers of area 11. Comparing the ratio of cellular mGluR
      expression to that of EAAT2, the mGluR/EAAT2 ratio showed that schizophrenics had
      a significantly increased mGluR/EAAT2 ratios in the pyramidal cell layers of all
      three PFC regions examined. The glutamate content of consecutive sections
      analyzed by high pressure liquid chromatography (HPLC), although decreased in
      schizophrenics did not reach significance and did not correlate with either EAAT2
      or mGluR mRNA content. These results are discussed in the light of current
      results on the neurochemistry and pharmacology of schizophrenia.

PMID- 9602130
TI  - Refolding of recombinant sulphonated procathepsin S and of reduced chicken
      cystatin; implications for renaturation experiments.
AB  - Kinetic stopped-flow measurements of refolding of the recombinant sulphonated
      procathepsin S from 6 M urea are presented. The experiments were performed using
      intrinsic tryptophan fluorescence and fluorescence of the hydrophobic probe 1
      anilino-naphthalene-8-sulfonate (ANS). Initially, (t1/2 = 3 +/- 1 ms) an
      intermediate with increased ANS fluorescence and protected tryptophan environment
      is formed. Much later, a slow increase in ANS fluorescence occurs with no
      accompanying changes in tryptophan fluorescence. The reaction of the slow ANS
      fluorescence increase correlates with the rate of aggregation as shown by the
      size exclusion chromatography (SEC). For comparison, the folding reactions of the
      reduced chicken cystatin were measured, both, by intrinsic tryptophan and
      extrinsic ANS fluorescence. An early intermediate forms very fast in the
      refolding of reduced chicken cystatin on 6-fold dilution from 5.7 M GuHCl (t1/2 =
      5 +/- 2 ms), similarly to that observed for the sulphonated procathepsin S. ANS
      fluorescence and tryptophan fluorescence decrease further (t1/2 = 100 +/- 50 ms)
      leading to a late, 'more structured' intermediate which is prone to dimerization.

PMID- 9602131
TI  - cDNA cloning and developmental expression of the porcine homologue of WT1.
AB  - Wilms' tumors occur most frequently in swines as sporadic tumors. To clarify the
      role of WT1 gene in the genesis of Wilms' tumors and genitourinary development,
      we have isolated the porcine homologue of the human WT1 gene (pWT1) and analyzed
      its expression in various organs including the kidney. The open reading frame of
      pWT1 cDNA was extremely homologous to the human counterpart: 94% identical at the
      nucleotide level and 98% at the polypeptide level. In particular, the zinc finger
      region was more than 97% similar to human WT1 gene at the nucleotide level and
      100% at the polypeptide level. pWT1 mRNA was found to be expressed in new-born
      kidney, spleen, testis, and embryonic kidneys, suggesting a possible association
      of pWT1 with the development of the genitourinary system. In conclusion, the
      nucleotide sequence and expression patterns in organs of pWT1 were similar to
      those of human WT1. Therefore, swines could provide good models for analyzing the
      contributions of WT1 gene to genitourinary development and genesis of Wilms'
      tumors.

PMID- 9602132
TI  - Attenuation of cell death mediated by membrane depolarization different from that
      by exogenous BDNF in cultured mouse cerebellar granule cells.
AB  - Membrane depolarization accompanying calcium (Ca2+) influx into neurons is
      thought to play an essential role in controlling the survival and death of
      cultured mouse cerebellar granule cells (CGCs). In this study, we sequentially
      controlled the survival and death of CGCs in culture and monitored the expression
      of several kinds of genes including brain-derived neurotrophic factor (BDNF)
      gene. Deprivation and subsequent induction of membrane depolarization by lowering
      and re-elevating the extracellular concentration of potassium chloride,
      respectively, led to death of CGCs and then to an attenuation of the death
      process depending upon the Ca2+ influx into CGCs through voltage-dependent
      calcium channels (VDCCs). De novo protein synthesis was critical for attenuating
      the death of non-depolarized CGCs. Accompanying this attenuation was an
      activation of c-fos and BDNF genes and an inactivation of c-jun and neurotrophin
      3 (NT-3) genes. The attenuation of cell death mediated by exogenous BDNF was only
      partial compared to that by membrane depolarization, suggesting that not only
      BDNF but also other factors could be involved in the membrane depolarization
      mediated attenuation of death of CGCs. In good agreement with this observation,
      the mode of activation of c-fos, c-jun, BDNF and NT-3 genes induced by exogenous
      BDNF was different from that induced by membrane depolarization. Thus, membrane
      depolarization effectively attenuates the death of non-depolarized CGCs, the mode
      of which seems to be different from that mediated by BDNF alone.

PMID- 9602133
TI  - Functional characteristics and the complete primary structure of ascidian
      gelsolin.
AB  - The body wall of the ascidian is composed of unusual multi-nucleated smooth
      muscle cells enriched with thin actin filaments containing troponin-tropomyosin
      which run along the longitudinal cell axis without being organized into striated
      structures. We purified an actin-binding protein of 80 kDa, tentatively termed
      80K protein, from the body wall muscle of ascidian, Halocynthia roretzi, and
      characterized the functional properties and molecular structures. In the presence
      of Ca2+, the 80K protein accelerated the initial phase of actin polymerization,
      namely the nucleation process, decreased the level of polymerization at the
      steady state, caused marked reduction in viscosity of an F-actin solution, and
      fragmented F-actin filaments, while in the absence of Ca2+, it remained
      associated with F-actin without severing the filaments. The interaction of the
      80K protein with actin was inhibited by phosphatidylinositol 4,5-bisphosphate
      (PIP2). When actin was polymerized in the presence of acrosome actin bundles from
      horseshoe crab sperm, the 80K protein inhibited the growth of actin filaments at
      the barbed end but not at the pointed end, indicating that the 80K protein
      functions as a barbed-end capping protein. In order to characterize the molecular
      structure of the 80K protein, cDNAs encoding this protein were isolated from the
      lambda gt11 cDNA library of the ascidian muscle by using a monoclonal antibody
      (AS23) specific for this protein and the entire sequence was determined. The
      deduced peptide sequence showed about 44% homology in amino acid residues with
      the human gelsolin sequence, and in addition, 6 repeating segments were observed
      in the sequence of the 80K protein as has been described in the gelsolin
      sequence. These results indicate strongly that the 80K protein belongs to the
      gelsolin family.

PMID- 9602134
TI  - Characterization of gene repertoires at mature stage of citrus fruits through
      random sequencing and analysis of redundant metallothionein-like genes expressed
      during fruit development.
AB  - We carried out a random sequencing of cDNA library derived from mature citrus
      fruit (Citrus unshiu Marc.) for identifying the gene repertoires expressed at the
      mature stage. Among 297 clones analyzed, 195 cDNA clones (65.7%) were putatively
      identified to previously characterized genes with optimized (OPT) scores of
      >/=200 through a homology search to DNA database, whereas 102 clones (34.3%)
      resulted in low OPT scores (<200) and did not show any significant sequence
      identity with previously published genes. Among them, clones homologous to
      metallothionein (MT)-like genes appeared 62 times, being mostly redundant, and
      accounting for about 20.9% of the total 297 clones. To gain a better
      understanding of the MT-like genes, two types of cDNA clones were isolated. One
      clone (CitMT36) resembled the type 2 MT gene containing Cys-X-Cys motifs in both
      N- and C-terminal, but the consensus sequence in the N-terminal domain, Cys-Cys
      and Cys-X-X-Cys was modified in CitMT36 to X-Cys and Cys-X-X-X, respectively. We
      suggest that these form a 'novel type 2' group of MT-like clones. The other clone
      (CitMT45) showed homology to type 3 MT-like genes, which have been found in
      mostly fruit tissues so far. By Southern blot analysis, both clones showed one or
      two bands, suggesting that both CitMT36 and CitMT45 are present in single or a
      few copies in the citrus genome. Transcripts of CitMT36 were evenly detected in
      all tissues examined, whereas those of CitMT45 were detected primarily in fruit
      during the developmental phase. Neither of the MT-like genes was induced in
      leaves by Zn and Cu. Collectively, MT-like genes from citrus would be regulated
      differentially depending on the fruit developmental stage and organs, indicating
      a change in their expression under the different physiological and molecular
      environment of fruit cells.

PMID- 9602135
TI  - Winged helix hepatocyte nuclear factor 3 and POU-domain protein brn-2/N-oct-3
      bind overlapping sites on the neuronal promoter of human aromatic L-amino acid
      decarboxylase gene.
AB  - The neuronal promoter of human aromatic l-amino acid decarboxylase gene has been
      analysed to elucidate the mechanisms of neuron type-specific expression. The (
      560/+92) promoter segment was sufficient to direct luciferase expression at a
      higher level in SK-N-BE neuroblastoma cells, than in CHP126 neuroepithelia, HepG2
      hepatoma or SK-Hep1 epithelioma cells. Deletions experiments showed that this
      segment contained a neuronal-specific (element T1) and a SK-N-BE-specific
      (element N1) cis-activating sequences. Element T1 (-72/-36) bound Sp1 and NF-Y
      proteins, and unidentified neuronal-specific factors. Element N1 (-102/-72) bound
      cell-specific factors, identified as HNF-3, N-Oct-3/Brn-2 and N-Oct-2. HNF-3
      proteins recognized the sequence TCAGTAAATA that matches the consensus motif. Oct
      1, N-Oct-2 and N-Oct-3 bound the AAATAATGC sequence that overlaps the HNF-3
      binding site. In addition, we show that the HNF-3 binding sites from aldolase C
      and HNF-3beta gene promoters also bind N-Oct-2 and N-Oct-3 proteins. These data
      suggest a functional interplay of winged helix/forkhead and POU-domain
      transcription factors on a variety of neuronal gene promoters.

PMID- 9602136
TI  - pZ402, an improved SV40-based shuttle vector containing a T-antigen mutant unable
      to interact with wild-type p53.
AB  - Shuttle vectors are useful tools for studying DNA replication and mutagenesis.
      SV40-based shuttle vectors are popular because of their ease of use and quick
      results. However, one complication with the use of SV40-based shuttle vectors is
      the interaction of cellular p53 protein with the T-antigen of SV40. Wild-type,
      but not mutant p53 has been shown to be involved in DNA replication and DNA
      repair. To address this concern, we have modified an SV40-based shuttle vector,
      pZ189, by exchanging the wt T-antigen for a mutant SV40 T-antigen, which is
      unable to bind with p53. This shuttle vector, pZ402, provides us with a tool to
      study DNA replication and genomic instability in cells with varying genetic
      backgrounds without interference from the interaction of T-antigen with p53.

PMID- 9602137
TI  - Acquisition of a new type of fructose-1,6-bisphosphatase with resistance to
      hydrogen peroxide in cyanobacteria: molecular characterization of the enzyme from
      Synechocystis PCC 6803.
AB  - We have previously described that Synechococcus PCC 7942 cells contain two
      fructose-1,6-bisphosphatase isozymes, designated F-I and F-II the former belongs
      to a new type of fructose-1,6-bisphosphatase, while the latter is a typical
      enzyme similar to the cytosolic and chloroplastic forms from eukaryotic cells
      [Tamoi et al., Arch. Biochem. Biophys., 334, 1996, 27-36]. The genes of F-I and F
      II were found in three species of cyanobacteria, Synechocystis PCC 6803, Anabaena
      7120, and Plectonema boryanum according to the results of Southern hybridization
      with a probe from the S. 7942 F-I and F-II genes. In Western blotting, antibody
      raised against the S. 7942 F-I cross-reacted with a protein band corresponding to
      the F-I in each crude extract from cyanobacterial cells, whereas the antibody
      against F-II failed to cross-react with any protein band corresponding to the F
      II. In cyanobacterial cells, only one form of F-I has been resolved by ion
      exchange chromatography at same concentration of NaCl as shown in the F-I of S.
      7942. The F-I from Synechocystis 6803 has been purified to electrophoretic
      homogeneity. The enzyme hydrolyzed both fructose 1,6-bisphosphate and
      sedoheptulose 1,7-bisphosphate. The apparent K(m) values of the enzyme for
      fructose 1,6-bisphosphate and sedoheptulose 1,7-bisphosphate were 57 +/- 2.4 and
      180 +/- 6.3 microM, respectively. The enzyme activity was inhibited by AMP with a
      Ki value of 0.57 +/- 0.03 mM for fructose 1,6-bisphosphate and 0.35 +/- 0.02 mM
      for sedoheptulose 1,7-bisphosphate. The enzyme showed a molecular mass of 168 kDa
      which was composed of four identical subunits. The activities of FBPase and
      SBPase from the F-I were resistant to hydrogen peroxide up to 1 mM. The
      nucleotide sequence of the S. 6803 F-I gene showed an open reading frame of 1164
      bp that encoded a protein of 388 amino acid residues (approx. molecular mass of
      41.6 kDa). The deduced amino acid sequences had homologous sequences with the S.
      7942 F-I.

PMID- 9602138
TI  - Promoter sequence and expression of the leucine-rich repeat gene LRR47: evidence
      for cytoplasmic and nuclear localization in Drosophila embryos and cells.
AB  - In Drosophila, proteins containing leucine-rich repeats (LRR) play diverse roles
      during embryonic development. In particular, they function in cell adhesion and
      cellular signalling and have in common the ability to mediate reversible protein
      protein interactions. The sequence and chromosomal location of Drosophila LRR47,
      which encodes a protein with eight LRR repeats, were reported previously. In this
      paper the 5' flanking region of the LRR47 gene is described and the initiation
      point for the maternal transcription unit is defined. LRR47 belongs to a
      subfamily of LRR proteins that have in common the ability to interact with ras
      GTPase. Whole-mount in situ hybridization studies show that the LRR47 transcript
      is uniformly distributed in early cleavage embryos but becomes depleted at the
      termini by the blastoderm stage. There is a specific requirement for ras function
      in the embryonic termini at this developmental stage. The distribution of LRR47
      protein in embryos and tissue culture cells was also studied. The protein is
      present in both the cytoplasm and nuclei of embryos until gastrulation and is
      seen to persist in the nuclei of the amnioserosa until later stages of
      development. The protein is also constitutively present in growing SL2 culture
      cells and again is present in both cytoplasm and nuclei. These results suggest
      that LRR47 function may be modulated in the cell or nuclear division cycle.

PMID- 9602139
TI  - Multiple pathways regulate the expression of genes encoding sodium channel
      subunits in developing neurons.
AB  - In primary cultures of fetal neurons, activation of sodium channels with either
      alpha-scorpion toxin or veratridine caused a rapid and persistent decrease of
      mRNAs encoding beta2 and different sodium channel alpha mRNAs. In contrast, beta1
      subunit mRNA was up-regulated by sodium channel activation. This phenomenon was
      calcium-independent. The effects of activating toxins on mRNAs of different
      sodium channel subunits were mimicked by membrane depolarization. An important
      aspect of this study was the demonstration that cAMP also caused rapid reduction
      of alphaI, alphaII and alphaIII mRNA levels whereas beta1 subunit mRNA was up
      regulated and beta2 subunit mRNA was not affected. Sodium channel activation by
      veratridine was shown to increase cAMP immunoreactivity in cultured neurons, but
      alphaII mRNA down-regulation induced by activating toxins was not reversed by
      protein kinase A antagonists, indicating that this phenomenon is not protein
      kinase A dependent. The effects of cAMP and membrane depolarisation were
      antagonized by the PKA inhibitor H89. These results are indicative of the
      existence of multiple and independent regulatory pathways modulating the
      expression of sodium channel genes in the developing central nervous system.

PMID- 9602140
TI  - Factors affecting the oligomeric state of NADP-malic enzyme from maize and wheat
      tissues: a chemical crosslinking study.
AB  - The different aggregational states of maize and wheat NADP-malic enzyme as
      affected by pH, temperature and various metabolites have been studied by the
      combined use of intersubunit crosslinking and denaturing polyacrylamide gel
      electrophoresis. The association/dissociation equilibrium is a pH-dependent
      process: pH values above 8.0 promote the tetramer formation, while lowering the
      pH shifts the equilibria towards dimers and monomers. Below pH 6.0, most
      molecules exist as monomers. In the same way, the temperature governs the
      equilibria between the different oligomeric states. As the temperature is lowered
      from 42 to 0 degrees C, a progressive dissociation into dimers and monomers is
      observed. Excess enthalpies are negative in all cases, but the overall process
      demands an input of Gibb's free energy. Consequently, the protein dissociation is
      an entropy-driven process. The presence of Mg2+ or glycerol induces aggregation
      in both enzymes, while increasing the ionic strength produces the opposite
      effect. The results suggest that changes in the equilibria between monomer, dimer
      and tetramer of NADP-malic enzyme could be the molecular basis for an effective
      regulation of the enzyme activity in vivo.

PMID- 9602141
TI  - XCIRP (Xenopus homolog of cold-inducible RNA-binding protein) is expressed
      transiently in developing pronephros and neural tissue.
AB  - The pronephros functions in the amphibian larval stage. It differentiates in
      certain presumptive regions of the amphibian embryo. The study of molecules
      functioning during pronephrogenesis is important for understanding the mechanism
      of kidney formation. Herein, we report a gene expressed during differentiation of
      the pronephros and neural tissues that we isolated by differential hybridization
      using our pronephros in-vitro induction system. The gene, XCIRP, is 887bp in
      length, and encodes a putative protein composed of 163 amino acid residues. The
      deduced protein contains two CS-RBDs (consensus sequence RNA-binding domain) and
      a glycine-rich domain, and is 74% identical to homologs from other species
      (mouse, rat and human). The expression of XCIRP increased rapidly during
      gastrulation, and XCIRP localization was seen in the presumptive pronephros and
      neural tissues. These findings suggest that XCIRP may play important roles in
      pronephrogenesis and neurogenesis.

PMID- 9602142
TI  - Rainbow trout Sox24, a novel member of the Sox family, is a transcriptional
      regulator during oogenesis.
AB  - We isolated a cDNA clone encoding a novel SRY-type HMG box (Sox) protein,
      designated Sox24, from a rainbow trout ovary cDNA library. On the basis of the
      HMG box amino acid sequence, Sox24 can be categorized into the same subgroup of
      Sox proteins as SOX4, SOX11, and SOX22. The proteins in this group also share a
      highly conserved sequence at the C-terminus. The Sox24 mRNA is expressed at high
      levels in the ovary, and in-situ hybridization localized its expression to
      oocytes. The recombinant protein containing the Sox24 HMG box region bound to an
      AACAAT sequence strongly in a gel retardation assay. Upon co-transfection into
      CHO cells, the full-length Sox24 transactivated transcription from a reporter
      plasmid through the AACAAT binding motif. We used GAL4/Sox24 chimeras with the
      DNA binding domain of yeast GAL4 at the N-terminus to map the transactivation
      function to the C-terminal region, which included the conserved sequence. These
      results suggest that Sox24 plays a role as a transcriptional regulator during
      oogenesis.

PMID- 9602143
TI  - Identification and characterization of the cell-associated binding protein for
      urinary trypsin inhibitor.
AB  - Urinary trypsin inhibitor (UTI) inhibits not only tumor cell invasion but also
      production of experimental and spontaneous metastasis. Cell-binding experiments
      indicated that human choriocarcinoma SMT-cc1 cells have specific binding sites
      for UTI on their cell surface. [Kobayashi et al., J. Biol. Chem. 269, 1994,
      20,642-20,647]. UTI binding protein (UTIBP) was purified to homogeneity by a
      combination of UTI-coupled affinity beads, preparative polyacrylamide gel
      electrophoresis and reverse phase HPLC. This protein is very similar to a
      truncated form of human cartilage link protein (LP). LP was identified
      structurally by its apparent molecular mass with and without deglycosylation
      treatment: Immunologically by the reactivity with anti-UTIBP antibody, and
      functionally by its ability to bind the NH2-terminal domain of UTI. UTI and UTIBP
      are distributed uniformly in the cytoplasm and/or over the cell surface of tumor
      cells and fibroblasts. The level of staining for hyaluronic acid, UTIBP and UTI
      is much lower in sections digested with hyaluronidase. These results suggest that
      the cell membrane-derived UTI-associated binding protein is the LP of
      proteoglycan-hyaluronic acid aggregates, which interacts with hyaluronic acid.
      Cell-associated LP may play a role in modulating protease activity to the
      environment close to tumor and fibroblast cell surface.

PMID- 9602144
TI  - MAP kinase phosphatase-1 mRNA is expressed in embryonic sympathetic neurons and
      is upregulated after NGF stimulation.
AB  - The family of Tyr/Thr protein phosphatases, called dual-specificity phosphatases,
      have been implicated in the feedback regulation of the MAP kinase cascade by
      dephosphorylating the MAP kinases. Using low stringent cDNA screening we have
      isolated a chicken homologue of the CL100 phosphatase also called MAP kinase
      phosphatase 1 (MKP-1). The chicken MKP-1 has 84% and 85.5% identity to the rat
      and human amino acid sequence, respectively. Using RNase protection assay and in
      situ hybridization we have found that MKP-1 mRNA is expressed at low levels in
      most tissues during development. In embryonic dorsal root and sympathetic ganglia
      MKP-1 mRNA expression increases with age. The expression in large cells in dorsal
      root ganglia suggests that it is neurons which express MKP-1 mRNA. We also show
      that MKP-1 mRNA is induced in dissociated embryonic sympathetic neurons after
      nerve growth factor stimulation. In addition, our results show that MKP-1 mRNA is
      induced after NGF stimulation of fibroblasts expressing the NGF receptor TrkA,
      suggesting that MKP-1 is upregulated after activation of the TrkA receptor. These
      data show that the MKP-1 gene is regulated in a tissue and temporal specific
      fashion with strong expression in the developing peripheral ganglia, and suggest
      that the activation of MKP-1 mRNA expression by NGF is a ubiquitously induced
      response to TrkA activation, independent of the cellular origin or type on which
      the TrkA receptor is active.

PMID- 9602145
TI  - Cloning, sequence analysis and expression of the basidiomycete Lentinus edodes
      gene uck1, encoding UMP-CMP kinase, the homologue of Saccharomyces cerevisae URA6
      gene.
AB  - Sequence analysis of the downstream region of the basidiomycete Lentinus edodes
      priB gene encoding a protein with a 'Zn(II)2Cys6 zinc cluster' DNA-binding motif
      (Endo, H., Kajiwara, S., Tunoka, O., Shishido, K., 1994. A novel cDNA, priBc,
      encoding a protein with a Zn(II)2Cys6 zinc cluster DNA-binding motif, derived
      from the basidiomycete Lentinus edodes. Gene 139, 117-121) suggested the presence
      of a Saccharomyces cerevisiae URA6 gene homologue encoding UMP kinase. We
      isolated a corresponding cDNA from a mature fruiting-body cDNA library of L.
      edodes. The nucleotide sequence of this was determined and compared with that of
      the genomic DNA, revealing that the URA6 gene homologue encodes 227 amino acids
      (aa) and is interrupted by four small introns. The deduced aa sequence showed an
      overall identity of 51.1% to that of the S. cerevisiae URA6 gene product. The
      URA6 homologue protein produced in Escherichia coli using the glutathione S
      transferase gene fusion system was found to catalyze the phosphoryl transfer from
      ATP to UMP and CMP efficiently and also to AMP and dCMP with lower efficiencies.
      Thus, the URA6 gene homologue was designated uck1 and its product UMP-CMP kinase.
      Northern-blot analysis showed that the uck1 is actively transcribed in the gill
      tissue of mature fruiting bodies of L. edodes, implying that uck1 may play a role
      during the formation of basidiospores occurs in the gill tissue.

PMID- 9602146
TI  - Characterization and expression of a heptaubiquitin gene from tomato.
AB  - Ubiquitin is highly conserved 76 amino acid protein involved, among other
      functions, in the selective degradation of proteins in the cell. From a tomato
      (Lycopersicon esculentum Mill. cv. Craigella) genomic library, we have isolated a
      clone encoding a polyubiquitin gene, designated ubq1-1 comprising seven repeats
      of ubiquitin and two C-terminal extension amino acids. The ubq1-1 gene contains
      an intron of 1128bp immediately upstream of the translation start codon. DNA
      sequence comparison revealed that the 5' and 3' non-coding regions of the tomato
      ubq1-1 gene are nearly identical to the sequence of a polyubiquitin cDNA clone
      isolated from potato (Garbarino et al., 1992; Plant Mol. Biol. 20, 235-244). The
      ubq1-1 gene is expressed in leaves to rather low levels in tomato, and the
      abundance of ubq1-1 transcripts is increased under heat shock conditions. For
      functional analyses, a chimeric gene construct containing the intron and 1.6kb of
      ubq1-1 sequence 5' to the intron fused to the gus reporter gene was introduced
      into the tobacco genome. In leaves of transgenic tobacco plants, reporter gene
      expression was generally lower from the ubq1-1 promoter than from the cauliflower
      mosaic virus 35S RNA promoter. In addition, the tomato ubq1-1 promoter was not
      found to respond to heat shock in transgenic tobacco plants. Histochemical
      analysis of the plants demonstrated localization of gus reporter gene activity in
      the vascular systems of the leaves and the roots. Deletion of the intron from the
      reporter gene construct markedly reduced reporter gene expression in transformed
      tobacco plants, thus suggesting that the intron may influence transcript levels
      deriving from the ubq1-1 promoter.

PMID- 9602147
TI  - GABAA receptor beta 2 and beta 3 subunits mRNA in the hippocampal formation of
      aged human brain with Alzheimer-related neuropathology.
AB  - Our work on the role of glutamate in Alzheimer's disease (AD)-related neuronal
      vulnerability and death provided significant insight into the potential
      contribution of the gamma-aminobutyric acid (GABA) neurotransmitter system as it
      participates in countering the neurotoxic effects of excessive glutamate receptor
      stimulation. Our previous studies demonstrate that beta2/3 GABAA receptor subunit
      immunoreactivity is relatively well preserved in hippocampi with AD pathology. To
      further elucidate the molecular basis for this observation, we employed in situ
      hybridization histochemistry to examine the levels of beta2 and beta3 receptor
      subunit mRNAs in the hippocampus of 19 elderly subjects presenting with a broad
      range of pathologic severity (i.e., Braak stage I-VI). Semi-quantitative analysis
      with film autoradiograms revealed that beta2 mRNA signal was highest in the
      granule cell layer, CA2 and CA1 subfields, while beta3 mRNA hybridization was
      highest in the granule cell layer, followed by CA2>/=CA3>/=CA1 regions. No
      significant difference in beta2 mRNA expression was detected among the
      pathologically mild, moderate or severe groups. In contrast, levels of beta3 mRNA
      in the pathologically severe group was significantly decreased compared to the
      mild group within all subregions examined except CA4. Our data suggest that
      alterations in the expression of GABAA receptor subunits in the AD hippocampus
      differ between specific receptor subunits with the amount of beta2 mRNA being
      relatively well-preserved, while beta3 mRNA levels were decreased.

PMID- 9602148
TI  - Structural basis for the electron transfer across the chromaffin vesicle
      membranes catalyzed by cytochrome b561: analyses of cDNA nucleotide sequences and
      visible absorption spectra.
AB  - We isolated cDNA clones for cytochromes b561 from sheep and porcine adrenal
      medullae using the RT-PCR technique. Comparison of the deduced amino acid
      sequences of various species showed that there are two fully-conserved regions in
      this cytochrome. In addition, one methionyl and six histidyl residues (potential
      heme ligands) are fully-conserved. Based on a plausible structural model in which
      a polypeptide spans the vesicle membranes six times and holds two heme B
      molecules, the first conserved sequence (69ALLVYRVFR77) is located on the
      extravesicular side of an alpha-helical segment and the second one (120SLHSW124)
      is located in an intravesicular loop connecting two alpha-helical segments,
      respectively. Consideration of the relative locations of the fully-conserved
      sequences, and the methionyl and histidyl residues in the model led to a proposal
      that the first and second conserved sequences are likely to form the binding
      sites for extravesicular ascorbic acid and intravesicular semidehydroascorbic
      acid, respectively. A mild alkaline-treatment of purified bovine cytochrome b561
      in oxidized state led to a specific loss of an electron-accepting ability from
      ascorbic acid for a half of the heme center, suggesting a distinct role for each
      of the two hemes.

PMID- 9602149
TI  - TrkA receptors delay C6-2B glioma cell growth in rat striatum.
AB  - Nerve growth factor (NGF) acts as an anti-mitogenic factor in C6-2B glioma cells
      stably expressing TrkA (C6trk+). To study the effect of TrkA on cell growth in
      vivo, we grafted mock and C6trk+ cells into the striatum of ACI nude rats. Thy
      1.1 and p75NTR immunohistochemistry revealed that wild type C6-2B cells formed a
      tumor mass in the striatum by 14 days. In contrast, C6trk+ transplanted rats did
      not show the presence of a significant tumor mass until 71 days. Analysis of this
      tumor showed that expression of TrkA was retained, but the synthesis of NGF was
      abolished. Our data encourage the speculation that expression of TrkA in
      glioblastoma in vivo will attenuate tumor progression.

PMID- 9602150
TI  - Preprotachykinin-A gene expression in the forebrain of Sardinian alcohol
      preferring and -nonpreferring rats.
AB  - Increasing evidence suggests that TKergic mechanisms might play a role in ethanol
      intake control. Preprotachykinin-A (PPT-A) mRNA brain levels were measured in
      Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats.
      PPT-A mRNAs were about 50% lower in sP than in sNP rats in the bed nucleus of the
      stria terminalis (BNST), whereas levels in the olfactory tubercle (Tu) were about
      30% higher in sP than in sNP rats. Our findings suggest that altered PPT-A gene
      expression might contribute to the different ethanol preference and intake of sP
      opposite to sNP rats.

PMID- 9602151
TI  - Amplification of target-specific, ligation-dependent circular probe.
AB  - We describe a novel polymerase chain reaction (PCR)-based gene amplification
      method utilizing a circularizable oligodeoxyribonucleotide probe (C-probe). The C
      probe contains two target complementary regions located at each terminus and an
      interposed generic PCR primer binding region. The hybridization of C-probe to a
      target brings two termini in direct apposition as the complementary regions of C
      probe wind around the target to form a double helix. Subsequent ligation of the
      two termini results in a covalently linked C-probe that becomes 'locked on to'
      the target. The circular nature of the C-probe allows for the generation of a
      multimeric single-stranded DNA (ssDNA) via extension of the antisense primer by
      Taq DNA polymerase along the C-probe and displacement of downstream strand,
      analogous to 'rolling circle' replication of bacteriophage in vivo. This
      multimeric ssDNA then serves as a template for multiple sense primers to
      hybridize, extend, and displace downstream DNA, generating a large ramified
      (branching) DNA complex. Subsequent thermocycling denatures the dsDNA and
      initiates the next round of primer extension and ramification. This model results
      in significantly improved amplification kinetics (super-exponential) as compared
      to conventional PCR. Our results show that the C-probe was 1000 times more
      sensitive than the corresponding linear hemiprobes for detecting Epstein-Barr
      virus early RNA. The C-probe not only increases the power of amplification but
      also offers a means for decontaminating carryover amplicons. As the ligated C
      probes possess no free termini, they are resistant to exonuclease digestion,
      whereas contaminated linear amplicons are susceptible to digestion. Treatment of
      the ligation reaction mixture with exonuclease prior to amplification eliminated
      the amplicon contaminant, which could also have been co-amplified with the same
      PCR primers; only the ligated C-probes were amplified. The combined advantages of
      the C-probe and thermocycling have a broad applicability for the detection of
      both DNA and RNA. Finally, we described a novel isothermal amplification method,
      ramification extension amplification, utilizing circular nature of C-probe and
      displacement activity of DNA polymerase.

PMID- 9602152
TI  - Porcine natural-killer-enhancing factor-B: oligomerisation and identification as
      a calpain substrate in vitro.
AB  - Natural-killer-enhancing factor-B (NKEF-B) (monomeric mass = 21.82 kDa) was
      purified from the cytosol of porcine red blood cells and its identity was
      established by microsequencing. NKEF-B oligomerisation was investigated by gel
      filtration and small-angle X-ray scattering (SAXS). Native NKEF-B readily forms
      disulphide-linked dimers, but when fully reduced, the protein forms discrete
      oligomers containing 16 +/- 1 monomers. A total of 40% of the purified enzyme was
      deduced to be cysteinylated, which is consistent with the modification of one or
      both of two putative active site cysteine residues. In vitro, NKEF-B was found to
      be a specific substrate of mu- and m-calpains, the calcium-dependent cysteine
      proteases. The cleavage events were followed by SDS-PAGE and the cleavage sites
      pinpointed by N-terminally sequencing the resulting digestion fragments. This in
      vitro cleavage data provides support to the hypothesis that calpromotin (NKEF-B),
      an erythron peroxiredoxin involved in the regulation of calcium-dependent
      potassium transport across the plasma membrane, is cleaved by calpain in vivo.

PMID- 9602153
TI  - mu-Opioid receptor-knockout mice: the role of mu-opioid receptor in
      gastrointestinal transit.
AB  - The role of mu-opioid receptor in gastrointestinal transit was investigated using
      mu-opioid receptor knockout mice (MOR-KO). Our result establishes unequivocally
      that inhibition of GI transit by morphine is a mu-opioid receptor mediated
      function. In addition, we show that neither delta nor kappa receptor agonist
      given supraspinally or peripherally are able to inhibit GI transit in MOR-KO
      animals. It was interesting to observe that basal GI motility was lower in MOR-KO
      (-/-) compared to heterozygous (+/-) and wild type (+/+) animals.

PMID- 9602154
TI  - Search for mutations near the alternatively spliced 8-amino-acid exon in the
      GABAA receptor gamma 2 subunit gene and lack of allelic association with
      alcoholism among four aboriginal groups and Han Chinese in Taiwan.
AB  - The alternatively spliced 8-amino-acid exon for the GABAA receptor gamma2 subunit
      gene (GABRC2) has been postulated to mediate behavioral actions of alcohol. A
      rapid search for splice-junction mutations near the 8-amino-acid exon using
      restriction enzymes which normally recognize sequences near or in the exon gave
      negative results among 217 alcoholics in four aboriginal groups (Ami, Atayal,
      Bunun and Paiwan) and Han Chinese in Taiwan. The role of the GABRC2 gene in
      alcoholism was further assessed by a comparison of allelic frequencies revealed
      by a NciI RFLP between case and control groups. No significant association of
      alcohol dependence with GABRC2 alleles was observed. These results suggest that
      the GABRC2 gene probably does not play an essential role in predisposition to
      alcoholism in the sample population.

PMID- 9602155
TI  - Differential expression of the alpha 9 nicotinic acetylcholine receptor subunit
      in neonatal and adult cochlear hair cells.
AB  - The expression of the alpha9 nicotinic acetylcholine receptor (nAChR) subunit was
      investigated in perinatal and adult rat cochleae using [35S] labeled cRNA in situ
      hybridization techniques. In the adult, alpha9 expression showed both
      longitudinal and radial gradients. The highest expression occurs over outer hair
      cells (OHCs) in basal regions, and particularly, OHCs in row 1. In contrast,
      expression over IHCs is lowest in basal regions and highest in apical regions.
      During embryonic and postnatal ages, the pattern of alpha9 expression differs.
      Expression of alpha9 was nearly equivalent over IHCs and OHCs. Additionally, the
      greater epithelial ridge, which is adjacent to IHCs before birth, shows a high
      level of alpha9 expression. These data are consistent with current models of
      efferent synaptogenesis and suggest that the expression of the alpha9 nAChR may
      be influenced by the arrival of efferent axons.

PMID- 9602156
TI  - Isolation, structural analysis and mapping of the functional gene of human
      ribosomal protein S26.
AB  - The nucleotide sequence of the gene of human ribosomal protein S26 has been
      assembled from cDNA and genomic PCR-amplified DNA fragments, and its
      transcription start site has been determined by primer extension. The gene is
      composed of four exons and three introns spanning 2027bp. Like other ribosomal
      protein genes of vertebrates, this gene contains a short first exon corresponding
      exactly to the short untranslated 5'- UTR. Its transcription start site is
      embedded in a polypyrimidine tract. Using PCR on DNAs from hybrid cell lines with
      a different set of human chromosomes, the intron-containing gene of ribosomal
      protein S26 was mapped to human chromosome 12.

PMID- 9602157
TI  - Analysis of the secondary structure of the catalytic domain of mouse Ras exchange
      factor CDC25Mm.
AB  - The minimal active domain (GEF domain) of the mouse Ras exchange factor CDC25Mm
      was purified to homogeneity from recombinant Escherichia coli culture. The 256
      amino acids polypeptide shows high activity in vitro and forms a stable complex
      with H-ras p21 in absence of guanine nucleotides. Circular dichroism (CD) spectra
      in the far UV region indicate that this domain is highly structured with a high
      content of alpha-helix (42%). Near UV CD spectra evidenced good signal due to
      phenylalanine and tyrosine while a poor contribution was elicited by the three
      tryptophan residues contained in this domain. The tryptophan fluorescence signal
      was scarcely affected by denaturation of the protein or by formation of the
      binary complex with H-ras p21, suggesting that the Trp residues, which are well
      conserved in the GEF domain of several Ras-exchange factors, were exposed to the
      surface of the protein and they are not most probably directly involved in the
      interaction with Ras proteins.

PMID- 9602158
TI  - Cloning and sequencing of three new putative toxin genes from Clostridium
      bifermentans CH18.
AB  - Three new open reading frames were found downstream from cbm71, a toxin gene from
      Clostridium bifermentans malaysia (Cbm) strain CH18. The first one (91bp
      downstream) called cbm72, is 1857bp long and encodes a 71727-Da protein (Cbm72)
      with a sequence similar to that of Bacillus thuringiensis delta-endotoxins. This
      protein shows no significant toxicity to mosquito larvae. The two others, cbm17.1
      (462bp) and cbm17.2 (459bp), are copies of the same gene encoding Cbm P18 and P16
      polypeptides and located 426bp and 1022bp downstream from cbm72, respectively.
      They encode 17189-Da and 17451-Da proteins with sequences 44.6% similar to that
      of Aspergillus fumigatus hemolysin; however, they were not hemolytic in the
      conditions tested.

PMID- 9602159
TI  - Differences in gene expression between sleep and waking as revealed by mRNA
      differential display.
AB  - In order to systematically investigate differences in gene expression between
      sleep and waking, mRNA differential display was used to examine mRNAs from the
      cerebral cortex of rats who had been spontaneously asleep, spontaneously awake,
      or sleep deprived for a period of 3 h. It was found that, while the vast majority
      of transcripts were expressed at the same level among these three conditions, the
      expression of a subset of mRNAs was modulated by sleep and waking. Half of these
      transcripts had known sequences in databases. RNAs expressed at higher levels
      during waking included those for the transcription factors c-fos, NGFI-A, and
      rlf, as well as three transcripts encoded by the mitochondrial genome, those for
      subunit I of cytochrome c oxidase, subunit 2 of NADH dehydrogenase, and 12S rRNA.
      As shown by in situ hybridization, the level of RNAs encoded by the mitochondrial
      genome was uniformly higher during waking in many cortical regions and in several
      extracortical structures. By contrast, mRNA levels corresponding to two
      mitochondrial protein subunits encoded by the nuclear genome were unchanged. This
      finding suggests the hypothesis that an increase in the level of mitochondrial
      RNAs may represent a rapid regulatory response of neural tissue to adapt to the
      increased metabolic demand of waking with respect to sleep.

PMID- 9602160
TI  - Cloning and functional expression of the rabbit transferrin gene promoter.
AB  - The transferrin gene is expressed in all mammals, mainly in the liver. A rabbit
      genomic library was screened using cDNA probes, and 8kb of 5' flanking sequence
      of the rabbit transferrin gene was cloned upstream of the cat reporter gene. The
      first 200 nucleotides of this promoter were sequenced. The rabbit transferrin
      promoter is highly homologous to the human and murine ones. Its functional
      activity was tested in the human hepatic cell line HepG2. Using transitory
      transfections in these cells, a proximal positive region, a negative region and a
      distal positive region located between -3.6 and -4.0kb were identified. This
      distal positive region sequence is highly conserved with the the human gene
      enhancer sequence, and contains an HNF3alpha binding site, the mutation of which
      totally abolished its effect in HepG2 and HuH7 cell lines. The rabbit transferrin
      5' flanking sequence thus shows a promoter organization very similar to that of
      the human gene, and the HNF3alpha binding site in the distal positive region
      presents the same functional importance in both genes.

PMID- 9602161
TI  - Characterization of aminopeptidase N from the brush border membrane of the larvae
      midgut of silkworm, Bombyx mori as a zinc enzyme.
AB  - Three GPI-anchored proteins, aminopeptidase N, alkaline phosphatase and alkaline
      phosphodiesterase I were released from the midgut brush border membrane of Bombyx
      mori by phosphatidylinositol-specific phopholipase C and the aminopeptidase N was
      purified to a homogeneous state. N-terminus and 6 internal sequences, one of
      which possessed part of zinc-binding motif, showed homology with those from other
      species. The zinc content in purified aminopeptidase N was estimated as
      approximately 0.72 mol/mol of the protein and 1,10-phenanthroline completely
      inhibited the enzyme activity, suggesting zinc requirement for the activity. The
      aminopeptidase N activity was inhibited not only by probestin and actinonin, but
      also strongly depressed by amastatin, while leuhistin and bestatin were less
      inhibitory. These suggest that the active site of aminopeptidase N might be
      structurally different from those of mammals. Calcium and magnesium ions
      stimulated the aminopeptidase N activity, but copper ion was rather inhibitory.
      Zinc ion showed bi-modal effect on the activity, i.e., stimulatory at low
      concentration, but inhibitory at higher than 100 microM. This inhibition was
      completely restored by EDTA. These results suggest that the aminopeptidase N
      possesses two zinc ion-binding sites with high and low affinity as essential and
      inhibitory one, as well as some regulatory metal-binding sites.

PMID- 9602163
TI  - Self-diffusion and self-association of lysozyme molecules in solution.
AB  - Self-diffusion of lysozyme molecules at the process of their self-association
      were studied by pulsed-field gradient nuclear magnetic resonance (NMR) at
      different lysozyme concentrations in solution. It was shown that in the intervals
      of pH from 1.8 to 4.0 and from 6.5 to 9.0, lysozyme self-diffusion coefficients
      were independent of pH value. In the interval of pH from 4.0 to 6.5, they
      decreased with increasing pH. Using self-diffusion data, estimations of the
      equilibrium constant k of the self-association reaction were made. For the model
      of indefinite self-association, k was found to be 264.5 +/- 0.5 l/M, and for its
      particular case-dimerization, 143 +/- 0.5 l/M. The dependence of the
      concentration of monomers and different associates on the total protein
      concentration was calculated.

PMID- 9602162
TI  - The claR gene of Streptomyces clavuligerus, encoding a LysR-type regulatory
      protein controlling clavulanic acid biosynthesis, is linked to the clavulanate-9
      aldehyde reductase (car) gene.
AB  - Two genes, claR and car, encoding proteins involved in clavulanic acid
      biosynthesis, have been found in a 2.8-kb BglII-EcoRI DNA fragment of
      Streptomyces clavuligerus adjacent to the region containing the cephamycin and
      clavulanic acid biosynthesis gene cluster. claR encoded a protein of 431 amino
      acids (deduced Mr 47080), that showed a significant degree of homology with
      several transcriptional activators of the LysR family. The ClaR protein contained
      two helix-turn-helix (HTH) motifs in the amino and carboxyl terminal regions. The
      second gene, car, encoded a protein of 247 amino acids (Mr 26629) that showed a
      strong similarity to oxydoreductases of the SDR family. Twelve amino acids of the
      amino-terminal region were identical to those previously obtained by Edman
      degradation of the purified clavulanic-9-aldehyde reductase of S. clavuligerus.
      Amplification of the claR gene in multicopy plasmids resulted in a threefold
      increase in clavulanic acid production and in a five- to sixfold increase of
      alanylclavam biosynthesis, whereas cephamycin production was significantly
      reduced both in defined and in complex media. By contrast, amplification of the
      car gene had no significant effect on clavulanic acid and alanylclavam or
      cephamycin production. Both claR and car are expressed as monocistronic
      transcripts; the level of transcript declined rapidly after 48h in complex media,
      but low sustained levels of both transcripts were observed in defined GSPG medium
      until 96h. claR and car were not significantly expressed in mutants disrupted in
      the ccaR gene, a regulatory gene that controls positively clavulanic acid and
      cephamycin biosynthesis. These results indicate that clavulanic acid and
      cephamycin biosynthesis in S. clavuligerus is controlled by a cascade of
      regulatory proteins that include CcaR and ClaR.

PMID- 9602164
TI  - New stable folding of beta-lactoglobulin induced by 2-propanol.
AB  - beta-lactoglobulin A has been studied in 2-propanol-water mixtures by means of
      circular dichroism, fluorescence and small angle X-ray scattering. At a low ionic
      strength, 2-propanol induces an increase in alpha-helix structure followed by a
      further transformation which gives rise to a new feature, rich of beta-sheet
      fragments. The second step of the secondary structure transformation is time
      dependent and depressed at high ionic strength. As a consequence, the tertiary
      structure is completely modified and a new stable protein folding may be
      hypothesized. Small angle X-ray scattering measurements reveal that 2-propanol
      induces a diffuse protein aggregation, but the complex equilibria among intra-
      and inter-molecular hydrophobic and electrostatic interactions may be modulated
      by balancing the ionic strength and/or alcohol percentage.

PMID- 9602165
TI  - Isolation of the Aspergillus nidulans sudD gene and its human homologue.
AB  - We have been studying the heat-sensitive bimD6 mutation of Aspergillus nidulans.
      At a restrictive temperature, the chromosomes of bimD6 mutant strains fail to
      attach properly to the spindle microtubules, and the mutant also displays a high
      rate of chromosome loss. We previously cloned the sudA gene, an extragenic
      suppressor of the heat-sensitive bimD6 mutation and showed that it coded for a DA
      box or SMC protein. SMC proteins have been demonstrated to function in chromosome
      condensation, segregation and global gene regulation. We have now cloned the sudD
      gene, another of the extragenic suppressor genes of the bimD6 mutation. The
      predicted SUDD protein is the founding member of a widely expressed protein
      family. Similar proteins are found in sequence databases for Saccharomyces
      cerevisiae, Caenorhabditis elegans, mammals and four species of archaebacteria.
      We have also cloned and sequenced a human cDNA that encodes the human homologue
      of SUDD and mapped the gene to 18q11.2. The predicted SUDD proteins from A.
      nidulans, Homo sapiens and S. cerevisiae all share a variety of features. The
      predicted proteins are approximately 60000Da in mass and have a serine-plus
      threonine content of about 11%. The evolutionary conservation of the proteins
      suggests an ancient origin and conserved function for these proteins.

PMID- 9602166
TI  - On the stability of the 24-meric hemocyanin from Eurypelma californicum.
AB  - The stability of the 24-meric hemocyanin from Eurypelma californicum towards
      various denaturants (GdnHCl, urea, urea derivatives and salts of the Hofmeister
      series) indicates that the quaternary structure is stabilized by hydrophilic and
      polar forces. Thus, the interaction between the seven different subunit types of
      this cheliceratan hemocyanin is comparable with that of the closely related
      crustacean hemocyanins. In contrast, no significant influence of divalent ions
      such as Ca2+ and Mg2+ on the stability is observed at pH 8.0 and pH 8.5 but not
      at pH 7.0. Studies, both in the presence of urea and GdnHCl indicate that the
      denaturation process consists of a dissociation of the oligomeric structure into
      intact subunits at lower concentrations of denaturants followed by denaturation
      of the subunits at higher concentrations of denaturants. No intermediates such as
      hexamers or dodecamers were detected after 24 h of incubation. This study also
      reveals that oligomerization has a stabilizing effect on the heterogeneous
      subunits. In addition, differences in the primary structures result in different
      stabilities of the seven different subunit types.

PMID- 9602167
TI  - Structural analysis of the human RFC-1 gene encoding a folate transporter reveals
      multiple promoters and alternatively spliced transcripts with 5' end
      heterogeneity.
AB  - The organization and structure of the human RFC-1 gene encoding a folate
      transporter were determined. The RFC-1 gene spans 22.5kb and was found to be
      distributed in eight exons, including five primary exons and three alternatives
      of exon 1. Most splice junctions conform to consensus sequences for such
      junctions. The human RFC-1 gene differs from the mouse and hamster genes both in
      terms of the total number of exons and in regard to alternatives of exon 1 which
      encode 5' end heterogeneity. Previously described cDNA variants (GenBank/EMBL
      accession no. U19720) are now shown to incorporate one of two alternatives (exons
      1a and 1b) to exon 1 and exons 2-6 as a result of RNA splicing. Another variant
      also described may not be full length in that it incorporates a probable
      alternative (exon 1c) to exon 1 along with exon 2 and a truncated exon 3. A
      relatively GC- rich region of the genome 5' of the alternatives to exon 1 appears
      to be distinctly promoter like and incorporates a number of putative cis-acting
      elements, including multiple SP1 sites, involved in the regulation of
      transcription. Primer extension analysis of this upstream region in two human
      cell types revealed a similar pattern of multiple transcription start sites (tsp)
      proximal to the 5' end of exon 1. However, there was a greater number of
      potential tsp within the region immediately upstream of exon 1b than within the
      regions upstream of exons 1a and 1c. The existence of true alternatives to exon 1
      in this gene incorporating different 5' ends indicates that its transcription is
      under the control of multiple promoters. The identity of two such promoters was
      obtained by functional deletion analysis, showing that expression of a luciferase
      reporter gene was directed separately by discrete stretches of nucleotide
      sequence proximal to exon 1a (promoter 1) or exon 1b (promoter 2) in transient
      transfection experiments. Promoter 1 appeared to have a three-fold lower basal
      activity than promoter 2, but was enhanced up to nine-fold in fusion constructs
      containing an SV40 enhancer element. Also, promoter 2 partly consists of a highly
      GC-rich direct repeat element containing at least three putative SP-1 and 3
      putative MZF1 sites. Finally, the activity of these promoters relative to each
      other was consistent with the results of primer extension analysis showing a
      greater multiple and usage of tsp within promoter 2 (exon 1b) than within
      promoter 1 (exons 1a and 1c), suggesting that the variant incorporating exon 1b
      was the most abundant.

PMID- 9602168
TI  - 8-Cysteine TGF-BP structural motifs are the site of covalent binding between
      mouse LTBP-3, LTBP-2, and latent TGF-beta 1.
AB  - The small latent TGF-beta complex often is associated with the latent TGF-beta
      binding protein (LTBP). Three LTBPs (LTBP-1, -2, and -3) have been isolated to
      date. Previous studies have shown that LTBP-1 binds the small latent TGF-beta 1
      complex through a disulfide bond between an 8-cysteine structural motif of LTBP-1
      (TGF-bp repeat) and the propeptide dimer of latent TGF-beta 1 (TGF-beta 1 latency
      associated peptide). There is indirect evidence that LTBP-2 and LTBP-3 also bind
      the latent TGF-beta complex, but the nature and location of the binding
      interaction are unknown. We have used immunoprecipitation, SDS-PAGE, and
      autoradiography to characterize the association between mouse LTBP-3 and the
      small latent TGF-beta 1 complex. We report that the second and third TGF-bp
      repeats of LTBP-3 covalently bind the latent complex, and we show a similar
      capability for the homologous TGF-bp repeats of mouse LTBP-2. The second TGF-bp
      repeat of LTBP-3 is unusual in that it has 9 cysteine residues instead of 8, and
      our results provide the first evidence that a TGF-bp repeat with an odd number of
      cysteine residues can covalently bind latent TGF-beta 1. Altogether, these
      results have important implications for TGF-beta biosynthesis and the regulation
      of TGF-beta activity.

PMID- 9602169
TI  - Arginine kinase is highly expressed in the compound eye of the honey bee, Apis
      mellifera.
AB  - We have cloned and sequenced a 1.68-kb cDNA encoding arginine kinase in the honey
      bee, Apis mellifera. The predicted protein shows a high level of identity to
      known arginine kinases in invertebrates and to other proteins belonging to the
      conserved family of ATP: guanidino phospho-transferases. The pattern of
      expression of arginine kinase has been investigated for the first time in various
      tissues including the brain, antennae and compound eye. Our results show that
      three isoforms of arginine kinase, transcribed from a single gene, are expressed
      in a characteristic pattern in major tissues of the honey bee. Arginine kinase
      mRNA is relatively abundant in the central nervous system and in the antennae.
      However, the highest level of expression, that is at least two to three times
      higher than in the brain, is found in the compound eye of the bee. By contrast,
      the levels of mRNAs encoding another metabolically important enzyme, alpha
      glycerolphosphate dehydrogenase (alpha-GPDH), are low in the eye. These findings
      suggest that arginine kinase is an important component of the energy releasing
      mechanism in the visual system that has high and fluctuating energy demands.
      Furthermore, our results support the role of phosphagen kinases in energy
      transport in polarised cells and are consistent with the role of arginine kinase
      as an energy shuttle that delivers ATP generated by mitochondria to high energy
      requiring processes, such as massive membrane turnover and pigment regeneration
      in the retina.

PMID- 9602170
TI  - Significance of the enzymatic properties of yeast S39A enolase to the catalytic
      mechanism.
AB  - The S39A mutant of yeast enolase (isozyme 1), prepared by site-directed
      mutagenesis, has a relative Vmax of 0.01% and an activation constant for Mg2+ ca.
      10-fold higher, compared with native enzyme. It is correctly folded. There is
      little effect of solvent viscosity on activity. We think that the loop Ser36
      His43 fails to move to the 'closed' position upon catalytic Mg2+ binding,
      weakening several electrostatic interactions involved in the mechanism.

PMID- 9602171
TI  - Characterization of two new cuticular genes specifically expressed during the
      post-ecdysial molting period in Tenebrio molitor.
AB  - In a previous study, we have isolated a cDNA, TM-ACP17, coding for a post
      ecdysial adult protein of Tenebrio molitor. After screening of a genomic library
      with TM-ACP17, we report isolation and sequencing of TM-ACP17 gene and a new
      gene, TM-LPCP29, coding for a larval-pupal protein. These two genes exhibit a
      common sequence of 15 nucleotides and a characteristic of most cuticular protein
      genes so far described: an intron interrupting the signal peptide. The deduced aa
      sequence of TM-LPCP29 exhibits a high percentage of Ala (26.5%) and Val (17.5%)
      and is highly hydrophobic. In the N-terminal part, the motif VAAPV is repeated
      ten times. Numerous histidine residues are present in the C- and N-terminal
      regions. A comparison is made with other cuticle protein sequences. Northern
      hybridization analysis showed that TM-LPCP29 is present during larval and mainly
      pupal post-ecdysial cuticle secretion. In-situ hybridization revealed that TM
      LPCP29 mRNA is expressed in epidermis and not in muscles or fat body.

PMID- 9602172
TI  - Analysis of eight cDNAs and six genes for intermediate filament (IF) proteins in
      the cephalochordate Branchiostoma reveals differences in the IF multigene
      families of lower chordates and the vertebrates.
AB  - We report the sequences of seven new cytoplasmic intermediate filament (IF)
      proteins of the cephalochordate Branchiostoma. The eight sequences currently
      known describe four subfamilies (A, B, C and D). All eight IF proteins show the
      short-length version of the coil 1b subdomain found in vertebrates and lack the
      additional 42 residues present in all nuclear lamins and the protostomic IF
      proteins. Although the lancelet is considered to be the closest relative of the
      vertebrates, it is difficult to relate its IF subfamilies unambiguously to a
      particular type I-IV subfamily of vertebrates. C1 and C2 have tail domains with
      two 64 residue repeats of coiled coil-forming ability, a structural feature
      unknown for IF proteins from vertebrates or protostomia. The epidermal protein D1
      shows only a slightly better identity score with vertebrate type II keratins than
      with type III proteins, but the D1 gene organization is that of type III
      proteins. The same holds for A1, A2, B1, B2 and C2 genes, although the latter has
      an additional and uniquely positioned intron. Antibodies (Ab) raised against
      recombinant C2 and D1 proteins reveal these proteins in epidermis, some internal
      epithelia and parts of the spinal cord. The results on exonic sequences, gene
      organization and expression suggest that Branchiostoma IF proteins may retain a
      largely archetypal condition, whereas the vertebrates have established the well
      known type I-IV IF system.

PMID- 9602173
TI  - c-Fos antagonizes the junD gene positive autoregulatory loop; a novel c-Fos role
      in promoter switching.
AB  - In contrast to c-jun and junB, the junD gene is constitutively expressed in
      quiescent cells. The junD promoter, therefore, may provide a paradigm for
      promoters mostly active in growth arrested cells. We report here that the human
      junD promoter is repressed by serum and TPA. Also, the ability of JunD to
      positively autoregulate its promoter is abolished under these conditions. The
      obtained promoter repression depends on the junD promoter TRE, suggesting the
      involvement of bZip proteins in this process. We found that c-Fos, a bZip protein
      known to be induced by serum and TPA, is sufficient to antagonize the JunD
      function. Furthermore, selective activation of the junD promoter by JunD is
      abolished by c-Fos with concomitant activation of the collagenase promoter. The
      latter contains a TRE that is transcriptionally activated in proliferating cells.
      We propose that c-Fos plays a novel role in intergenic promoter switching,
      downregulating quiescent-state related genes while simultaneously upregulating
      proliferation-state specific genes.

PMID- 9602175
TI  - Existence of a bovine LINE repetitive insert that appears in the cDNA of bovine
      protein BCNT in ruminant, but not in human, genomes.
AB  - A novel protein, BCNT, originally isolated from bovine brain and named after
      Bucentaur, contains an internal portion that is translated from part of bovine
      LINE repetitive sequence (Bov-B LINE). Human cDNA highly homologous to the bovine
      bcnt (bbcnt) cDNA has been isolated but does not contain a sequence similar to
      the Bov-B LINE insert (Nobukuni, T., Kobayashi, M., Omori, A., Ichinose, S.,
      Iwanaga, T., Takahashi, I., Hashimoto, K., Hattori, S., Kaibuchi, K., Miyata, Y.,
      Masui, T., Iwashita, S., 1997. An Alu-linked repetitive sequence corresponding to
      280 amino acids is expressed in a novel bovine protein, but not in its human
      homologue. J. Biol. Chem. 272, 2801-2807). In this study, we conducted a
      polymerase chain reaction analysis to investigate whether such a Bov-B LINE
      insert is present in bcnt orthologs in other animals and in the genomic sequence
      of the human BCNT (hBCNT) gene. The results indicate that the Bov-B LINE insert
      is present in the genomic sequences of bcnt orthologs from sheep, goats, axis
      deer, and mouse deer (chevrotain), that is in Ruminantia, but not in pigs or
      human. Analysis of the bbcnt genomic sequence around the Bov-B LINE insert
      revealed a large part of the inserted Bov-B LINE sequence to be included in an
      exon; this is followed by a 54-nucleotide sequence that is highly homologous to
      Bov-B LINE in the 3'-side intron. The hBCNT gene was isolated and found to
      consist of seven exons and six introns, among which the intron corresponding to
      the Bov-B LINE insertion site in the bbcnt genome is 16.5kb in length with no
      sequence similar to Bov-B LINE. Based on these results, it seems likely that the
      Bov-B LINE insert is derived from a long Bov-B LINE repetitive sequence
      transposed to an ancestral bcnt gene in Ruminantia and reformed as a new exon
      through new splicing sites in the transposed sequence.

PMID- 9602174
TI  - A dynein light chain of sea urchin sperm flagella is a homolog of mouse Tctex 1,
      which is encoded by a gene of the t complex sterility locus.
AB  - The outer-arm dynein of sea urchin sperm flagella contains six light chains with
      molecular masses of 23.2, 20.8, 12.3, 11.5, 10.4 and 9. 3kDa. We have cloned a
      cDNA for the 12.3kDa polypeptide (light chain 3) and found that this protein is
      highly homologous to mouse Tctex1, a protein encoded by a member of the multigene
      family in the t complex region that is involved in male sterility and the
      development of the germ cells. Tctex1 has recently been shown to be homologous to
      a light chain of cytoplasmic dynein. Therefore, the cytoplasmic dynein light
      chain has been implicated in the mechanism for the transmission ratio distortion
      (meiotic drive) that is characteristic of t haplotypes in mice. Our present
      finding, however, indicates that axonemal light chain 3 must be considered
      equally important.

PMID- 9602176
TI  - A high-copy-number ADE2-bearing plasmid for transformation of Candida glabrata.
AB  - The Candida glabrata ADE2 gene encoding aminoimidazole ribonucleotide (AIR)
      carboxylase (EC 4.1.1.21) was isolated by complementation of the ade2-1 mutation
      in Saccharomyces cerevisiae. The predicted amino acid (aa) sequence is 75%
      identical to that of S. cerevisiae. Integrative transformation was used to
      produce a C. glabrata strain bearing a deletion of ADE2 coding sequences. A high
      copy-number shuttle vector bearing the ADE2 gene was constructed and contains a
      fragment of S. cerevisiae mitochondrial (mt) DNA that confers the ability to
      replicate autonomously in C. glabrata.

PMID- 9602177
TI  - America: where kids are getting killed.

PMID- 9602178
TI  - Escherichia coli O157:H7: assessing and minimizing the risk from farm to fork.

PMID- 9602179
TI  - Neonatal apnea, bradycardia, or desaturation: does it matter?

PMID- 9602180
TI  - Screening for diabetic retinopathy in childhood: do the ayes have it?

PMID- 9602181
TI  - FRAXA and FRAXE: to test or not to test?

PMID- 9602182
TI  - Making a "dent" in hereditary hypercalciuric nephrolithiasis.

PMID- 9602183
TI  - Hemoglobin E beta-thalassemia: an increasingly common disease with some
      diagnostic pitfalls.

PMID- 9602184
TI  - Role of the prenatal environment in the development of obesity.
AB  - Establishing that prenatal life is a critical or sensitive period for the
      development of obesity may focus basic research and clinical prevention efforts
      on this period. This review summarizes evidence that the intrauterine environment
      influences the risk of later obesity and considers the mechanisms by which this
      may occur. The association between birth weight and adult weight suggests that
      there are enduring effects of the intrauterine environment on later obesity risk.
      We examine whether the maternal factors of diabetes, obesity, and pregnancy
      weight gain alter the intrauterine environment and thereby increase the risk of
      later obesity in the offspring. Of these maternal factors, evidence is strongest
      for the role of maternal diabetes. No single mechanism explains how these
      maternal factors could change the intrauterine environment to increase obesity
      risk. However, all potential mechanisms involve an altered transfer of metabolic
      substrates between mother and fetus, which may influence the developing structure
      or function of the organs involved in energy metabolism.

PMID- 9602185
TI  - Risk of hemolytic uremic syndrome after sporadic Escherichia coli O157:H7
      infection: results of a Canadian collaborative study. Investigators of the
      Canadian Pediatric Kidney Disease Research Center.
AB  - OBJECTIVES: The objectives of this study were to better estimate the age-specific
      risks of hemolytic uremic syndrome (HUS) and hemolytic anemia after Escherichia
      coli O157:H7 infection among a representative cohort of both referred and
      nonreferred children with documented illness from the province of Alberta and to
      compare this with the rates in children evaluated at referral centers in the rest
      of Canada. STUDY DESIGN: Children with HUS or E. coli O157:H7 gastroenteritis
      were eligible if they were < 15 years of age. Hemoglobin, blood smear,
      urinalysis, and serum creatinine were obtained 8 to 10 days after the onset of
      diarrhea to ascertain for hemolysis, anemia, thrombocytopenia, and renal injury.
      Subjects were monitored for 1 month. RESULTS: From June 1991 to March 1994, HUS
      was diagnosed in 205 children. Of these 77% had evidence of E. coli O157:H7
      infection. A further 582 children had E. coli O157:H7 gastroenteritis, of whom 18
      had hemolytic anemia. The risk of HUS after E. coli O157:H7 infection in Alberta
      was 8.1% (95% confidence interval, 5.3 to 11.6) compared with 31.4% in referral
      centers in the rest of Canada. In Alberta the highest age-specific risk of
      HUS/hemolytic anemia was 12.9% in those < 5 years of age. CONCLUSIONS: These data
      will help guide clinical care and provide a basis for estimating the sample sizes
      required in future treatment trials for the secondary prevention of HUS.

PMID- 9602186
TI  - Frequency and timing of recurrent events in infants using home cardiorespiratory
      monitors.
AB  - OBJECTIVE: To determine the incidence, type, timing, and factors predictive of
      recurrent significant events in infants with home cardiorespiratory monitors.
      STUDY DESIGN: We reviewed data accumulated for 147 patients with an event
      recorder type of monitor. The infants were allocated to one of four diagnostic
      categories: apparent life-threatening events (ALTE, n = 73), former premature
      infants with persistent apnea and bradycardia (n = 29), siblings of victims of
      sudden infant death syndrome (SIDS) (n = 24), and parental anxiety after a
      nonsignificant event (n = 21). RESULTS: Compliance with monitoring was excellent;
      the monitors were used on 94% of the prescribed days. Fifty-three (36%) of 147
      infants had significant events; of those, 46 (87%) experienced their first event
      during the first month of monitoring, and 69% of the events occurred during that
      first month. The most prevalent event type was a bradycardic event. Among infants
      in the ALTE group, events during the initial investigation period predicted the
      likelihood of events at home; 2 of the 47 infants (4%) with negative results for
      an investigation and no events recorded in hospital had apnea, and 4 had a
      bradycardic event (9%). In contrast, when significant events were recorded in
      hospital, the events were likely to recur at home (69% and 35% of the infants had
      apnea or bradycardia, respectively; p < 0.001). CONCLUSION: Because most apnea,
      bradycardia, and recurrent clinical events began during the first month of
      monitoring, we emphasize the need for vigilant follow-up care of infants
      immediately after institution of home monitoring. Readmission for investigation
      is warranted in infants with severe or multiple recurrent events.

PMID- 9602187
TI  - Diabetic retinopathy in pediatric patients with type-1 diabetes: effect of
      diabetes duration, prepubertal and pubertal onset of diabetes, and metabolic
      control.
AB  - OBJECTIVE: The objective of this study was to determine the contribution of
      prepubertal and pubertal onset and duration of diabetes to the development of
      diabetic retinopathy. STUDY DESIGN: A total of 1391 standardized fundus
      examinations (stereo fundus-photography) were performed in 441 children or
      adolescents with type-1 diabetes (median age 15.5 years, median duration of
      diabetes 6.3 years). RESULTS: Mild nonproliferative retinopathy was present in 72
      patients (median age 19.9 years). Life table analysis revealed a median duration
      of diabetes until retinopathy was first diagnosed at 16.6 years (95% confidence
      interval: 15.3 to 18.3). Patients were stratified according to diabetes onset
      before or in puberty (> or = 10.4 years in girls, > or = 12.2 years in boys). In
      children with a prepubertal onset of diabetes, retinopathy occurred after a
      pubertal duration of 10.9 years compared with 15.1 years in children with onset
      of diabetes in puberty (p < 0.01), demonstrating the additional risk conveyed by
      the prepubertal years of diabetes. Long-term metabolic control had a significant
      influence on the prevalence of retinopathy: patients with a median HbA1c > or =
      7.5% had development of retinopathy on average after 15.5 years compared with
      18.3 years in patients with lower HbA1c values (p < 0.05). CONCLUSION: Both
      prepubertal and pubertal duration of diabetes are relevant for the development of
      background retinopathy. Good metabolic control should be attempted irrespective
      of age.

PMID- 9602188
TI  - The prevalence of the FMR1 and FMR2 mutations among preschool children with
      language delay.
AB  - We examined the prevalence of the fragile X mental retardation (FMR1) full
      mutation and fragile X E mutation (FMR2) among preschoolers evaluated for
      language delay. A total of 534 preschoolers recruited from a Developmental
      Pediatric or Speech and Language Disorders clinic were tested with Southern blot
      and polymerase chain reaction DNA analyses; 3 were found to have the FMR1 full
      mutation. None of the 534 children tested positive for the FMR2 full mutation;
      however, 3 children had unusually small FMR2 alleles suggestive of FMR2
      deletions. Screening for fragile X among language-delayed preschoolers is
      warranted, particularly when there is a family history of mental retardation, but
      regardless of sex or the presence of behavioral or physical features associated
      with the fragile X phenotype. The potential benefit of screening for FMR2
      alterations is an unexpected implication of the study and is worthy of continued
      exploration.

PMID- 9602189
TI  - An outbreak of salmonellosis among children attending a reptile exhibit at a zoo.
AB  - OBJECTIVE: In January 1996, an outbreak of diarrhea caused by Salmonella
      Enteritidis occurred in children attending a Komodo dragon exhibit at a
      metropolitan zoo. We sought to determine the extent of the outbreak and mode of
      transmission. STUDY DESIGN: A case-control study was conducted. Controls were
      randomly selected from zoo membership lists and matched to patients by age group
      and date of exhibit visit. RESULTS: Of 65 patients identified, 39 had confirmed
      and 26 had suspected cases. The median age was 7 years (range, 3 months to 48
      years); 55% were enrolled in the case-control study. No patients and two (4%)
      controls reported touching a dragon; however, 83% of patients but only 52% of
      controls touched the wooden barrier that surrounded the dragon pen (odds ratio =
      4.0, 95% CI 1.2 to 13.9). Washing hands at the zoo after visiting the dragons was
      highly protective (OR = 0.14, 95% CI 0.03 to 0.7). Cultures from the patients,
      one dragon, and the exhibit barriers yielded Salmonella Enteritidis, phage type
      8. On the basis of an attack rate of 4.3% among exhibit attendees under 13 years
      old on whom data were collected, we estimate that 315 additional cases of
      salmonellosis occurred among visitors in this age group. CONCLUSION: This large
      outbreak demonstrates the importance of environmental contamination in the
      transmission of Salmonella from reptiles, and the protective value of hand
      washing. Recommendations regarding reptile exhibits and reptilian pets should
      emphasize this indirect route.

PMID- 9602190
TI  - Encephalopathy and progression of human immunodeficiency virus disease in a
      cohort of children with perinatally acquired human immunodeficiency virus
      infection. Women and Infants Transmission Study Group.
AB  - OBJECTIVE: To describe the incidence, predictors, and survival of children with
      human immunodeficiency virus (HIV) encephalopathy followed in the Women and
      Infants Transmission Study cohort. STUDY DESIGN: Retrospective review of clinical
      and immunologic staging of perinatally HIV-infected infants, based on the 1994
      Centers for Disease Control and Prevention Classification System. RESULTS: Data
      were available for 128 HIV-infected children, with a median follow-up of 24
      months. HIV encephalopathy was diagnosed in 27 (21%) of children. Median survival
      after diagnosis was 14 months. Of children with encephalopathy, 74% had at least
      moderate immunosuppression by the time of diagnosis. Encephalopathy represented
      the first acquired immunodeficiency syndrome-defining condition in 67%, and the
      only one in 26% of children. Hepatosplenomegaly or lymphadenopathy during the
      first 3 months of life was diagnosed in 63%, in contrast to 29% of those without
      encephalopathy (p value = 0.001). Cardiomyopathy was present in 30% of the
      children with encephalopathy versus 2% of those without encephalopathy. High
      viral load in infancy was associated with increased risk of encephalopathy but
      was not predictive of age at onset. CONCLUSIONS: Encephalopathy in children with
      HIV is common and is associated with high viral load, immunodeficiency, and
      shortened survival. Encephalopathy was more likely to develop in infants with
      early signs and symptoms of HIV, although age at onset could not be predicted.

PMID- 9602191
TI  - The early diagnosis of periventricular leukomalacia in premature infants with
      positive rolandic sharp waves on serial electroencephalography.
AB  - OBJECTIVE: The objective of this study was to determine the specificity and the
      sensitivity of electroencephalography's positive rolandic sharp waves (PRSW) for
      the diagnosis of cystic and noncystic periventricular leukomalacia (PVL).
      METHODS: A retrospective study was performed on a population of 765 premature
      infants alive after 5 days who were divided into two groups; 166 infants born
      before 28 weeks (group 1) and 599 born between 28 and 32 completed weeks'
      gestation (group 2). Each infants underwent repeated ultrasound scanning and
      electroencephalography recordings during the first weeks of life. Magnetic
      resonance imaging was performed in infants with persisting hyperechoic
      periventricular densities on ultrasonography. RESULTS: A total of 83 (10.8%)
      newborns had PVL; 65 (8.5%) had cystic PVL PRSW, observed in 55 (7.2%) infants,
      always preceded the ultrasonic detection of cysts. PRSW were very specific
      markers of PVL in both groups (100% in group 1, 99.8% in group 2). PRSW
      sensitivity was found dependent on gestational age: 32.4% in group 1 in contrast
      to 87.8% in group 2. CONCLUSION: PRSW are an early and very specific marker of
      PVL in premature infants.

PMID- 9602192
TI  - Short interpregnancy interval and the risk of disabling cerebral palsy in a low
      birth weight population.
AB  - OBJECTIVE: The objective of this study was to investigate the relation of short
      interpregnancy interval and cerebral palsy (CP) in a low birth weight population
      in whom neonatal brain injury was systematically ascertained in the newborn
      period. STUDY DESIGN: We used data from a prospective cohort study of 1105
      infants born < or = 2000 gm, designed to study the cause and consequences of
      neonatal brain injury. Of the 777 children with data on brain injury and CP, 382
      were born to multiparous women, and 375 had information available to calculate
      interpregnancy interval, defined as the number of days from the end of the last
      pregnancy to conception of the index pregnancy. RESULTS: In the presence of the
      strong explanatory power of neonatal brain injury, short interpregnancy interval
      maintains an independent risk for disabling CP. CONCLUSION: In this cohort of low
      birth weight infants, short interpregnancy interval appears to represent a
      significant risk for the development of disabling CP.

PMID- 9602193
TI  - The application of a risk-approach model to reduce mortality in infancy.
AB  - OBJECTIVES: To examine the utility of a risk-approach model in identifying
      infants at greater risk of postneonatal mortality (PNM) and to determine whether
      there is a relationship between PNM and linkage of at-risk infants to primary
      health care. METHODS: The Sheffield Birth Score instrument was applied to 90,846
      newborn infants to determine high-score (HS) and low-score (LS) infant risk
      groups. Health care visit data were collected on all HS infants who were referred
      for primary pediatric care. Mortality rates were calculated for both HS and LS
      infant groups and for HS infants who were linked and not linked to care. RESULTS:
      The HS infant group was at significantly greater risk of PNM (p < 0.0001). The
      linked group had a lower PNM rate (p < 0.05), and linked/not-linked group
      differences were noted for 11 of 20 variables. When these 11 variables and the
      linked/not-linked variable were entered into a logistic regression analysis,
      linkage was the only significant variable (p < 0.01) in predicting PNM.
      CONCLUSIONS: The Sheffield Birth Score differentiated at birth those infants who
      were at greater risk of PNM. The lower incidence of PNM among linked HS infants
      suggests a promising argument for early pediatric intervention. Further research
      to clarify specific factors that influence health care participation decisions is
      suggested.

PMID- 9602194
TI  - Pulmonary toxicity associated with nitric oxide in term infants with severe
      respiratory failure.
AB  - We prospectively analyzed airway specimens from 24 newborn infants. Inhaled
      nitric oxide (< or = 20 ppm for 1 to 4 days to 12 infants) did not affect the
      concentrations of the lipid peroxidation product, the surface activity, or the
      cytokines (interleukin-1, granulocyte-macrophage colony-stimulating factor,
      interleukin-1 receptor antagonist). Nitrotyrosine was detected after 10 days of
      life in the two infants requiring prolonged ventilation, suggesting toxicity of
      endogenous nitric oxide.

PMID- 9602195
TI  - Methotrexate in patients with Crohn's disease after 6-mercaptopurine.
AB  - OBJECTIVE: The objective of this study was to describe the clinical outcome of
      children with Crohn's disease treated with subcutaneous methotrexate.
      SUBJECTS/METHODS: Fourteen patients (10 boys) with extensive Crohn's disease
      diagnosed at a mean age of 10.6 +/- 3.6 years had previously received various
      medical therapies for 4.3 +/- 4.0 years. Because of the severity of their
      disease, 6-mercaptopurine had been introduced but discontinued because of the
      patients' failure to respond (n = 11) or the development of pancreatitis (n = 3).
      Subsequently, low-dose, weekly, subcutaneous methotrexate was initiated.
      Pediatric Crohn's Disease Activity Index scores and prednisone requirement were
      followed as outcome measures. RESULTS: Overall, 9 (64%) of the 14 patients showed
      improvement, including 6 (55%) of 11 patients who had previously received an
      adequate trial of 6-mercaptopurine and all three patients who were intolerant of
      6-mercaptopurine. Improvement in clinical and laboratory measures occurred by 4
      weeks and were similar whether (n = 8) or not (n = 6) the dose of corticosteroids
      was increased before the start of subcutaneous methotrexate. Three patients were
      tapered from their initial methotrexate dose after the minimization of
      corticosteroids and remain well. One patient receiving daily corticosteroids died
      suddenly after acute onset of illness. Among patients responding, methotrexate
      was discontinued because of side effects (n = 2) or electively (n = 2). Of the
      latter two patients, one has resumed methotrexate after disease relapse, whereas
      the other patient has had a sustained remission. CONCLUSIONS: Low-dose, weekly,
      subcutaneous methotrexate can induce remission in some pediatric patients with
      Crohn's disease who fail to adequately respond to other immunomodulator
      medications.

PMID- 9602196
TI  - Ultrasonographic and clinical predictors of intussusception.
AB  - OBJECTIVE: The objective of this study was to determine the positive and negative
      clinical predictors of intussusception and the correlation of ultrasonography and
      air enema in establishing this diagnosis. STUDY DESIGN: This was a prospective
      descriptive cohort study. SETTING: This study was performed in a tertiary care
      pediatric emergency department. PARTICIPANTS: Eighty-eight of 245 candidates were
      assessed for clinical predictors of intussusception. All 245 cases were examined
      for correlation between ultrasonography and air enema. INTERVENTIONS: A
      questionnaire, ultrasonography, and air enema were used. RESULTS: Thirty-five of
      the 88 patients assessed for clinical predictors were positive for
      intussusception. Significant positive predictors were right upper quadrant
      abdominal mass (positive predictive value [PPV] 94%), gross blood in stool (PPV
      80%), blood on rectal examination (PPV 78%), the triad of intermittent abdominal
      pain, vomiting, and right upper quadrant abdominal mass (PPV 93%, p = 0.0001),
      and the triad with occult or gross blood per rectum (PPV 100%, p = not
      significant). Significant negative predictors were a combination of > or = 3 of
      10 clinically significant negative features (negative predictive value 77%, p =
      0.035). Of the total 245 cases, intussusception (as confirmed by doughnut,
      target, or pseudokidney sign) was ruled out by ultrasonography in 97.4%.
      Alternate ultrasound findings comprised 27% of negative cases. CONCLUSIONS:
      Excellent positive predictors of intussusception were identified prospectively.
      Although no reliable negative predictors were found, patients at low risk may be
      screened by ultrasonography.

PMID- 9602197
TI  - A controlled trial of health promotion programs in 11-year-olds using physical
      activity "enrichment" for higher risk children.
AB  - OBJECTIVE: To evaluate the short and long term benefits of a school and home
      based physical activity "enrichment" program for children at higher risk of
      cardiovascular disease as identified by cluster analysis. STUDY DESIGN: During
      two 10-week school terms, 800 11-year-olds took part in a randomized controlled
      trial with the standard physical activity and nutrition program in six schools,
      the standard program in a further seven schools but with the addition of physical
      activity enrichment for higher risk children in those schools, and no program in
      five control schools. Cluster analysis identifying the 29% or so highest risk
      children used systolic blood pressure, percent body fat, physical fitness, and
      blood cholesterol. RESULTS: Fitness improved significantly in program schools,
      particularly with enrichment in higher risk boys. Substantial improvements
      persisted 6 months later in girls from program schools. At "Enrichment" schools,
      cholesterol showed significant benefits in higher risk girls and, 6 months later,
      in both boys and higher risk girls. Sodium intake and, in girls, subscapular
      skinfolds were lower in "Enrichment" schools when the program ended, but not 6
      months later. CONCLUSION: Two-semester health programs with physical activity
      enrichment for higher risk children can produce benefits sustained for at least 6
      months. Improvements extend to lower risk children exposed indirectly to the
      enrichment. Attenuation of effects on diet and body composition in the longer
      term suggest the need for on-going programs.

PMID- 9602198
TI  - Early nebulized budesonide in the treatment of bronchiolitis and the prevention
      of postbronchiolitic wheezing.
AB  - OBJECTIVE: To determine the effectiveness of nebulized budesonide in the
      treatment of acute bronchiolitis and in the prevention of postbronchiolitic
      wheezing. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial was
      performed. PATIENTS: Forty infants with bronchiolitis (83% RSV), mean age 13.5
      weeks (range 4 to 41 weeks), were admitted to the Royal Alexandra Children's
      Hospital, Brighton, UK. METHODS: Twenty-one infants received nebulized budesonide
      1 mg every 12 hours for 5 days, then 500 micrograms every 12 hours continuing to
      a total of 6 weeks. Nineteen received nebulized placebo (0.9% saline) for 6
      weeks. A clinical scoring system was used to rate acute symptoms, and diary cards
      were used to assess persistent respiratory symptoms over a 6-month follow-up
      period. RESULTS: No significant differences were found between the budesonide and
      placebo groups in change in clinical score 48 hours after trial entry, mean
      oxygen requirements, or length of hospital stay during the acute illness. At 6
      month follow-up, the two groups did not differ significantly in prevalence of
      wheeze, respiratory symptom scores, or proportion requiring bronchodilators or
      steroids. CONCLUSION: This study did not demonstrate that a 6-week course of
      nebulized budesonide reduced the symptoms of acute bronchiolitis or prevented
      postbronchiolitic wheezing.

PMID- 9602199
TI  - Children with asthma have improved pulmonary functions after massage therapy.
AB  - Thirty-two children with asthma (16 4- to 8-year-olds and 16 9- to 14-year-olds)
      were randomly assigned to receive either massage therapy or relaxation therapy.
      The children's parents were taught to provide one therapy or the other for 20
      minutes before bedtime each night for 30 days. The younger children who received
      massage therapy showed an immediate decrease in behavioral anxiety and cortisol
      levels after massage. Also, their attitude toward asthma and their peak air flow
      and other pulmonary functions improved over the course of the study. The older
      children who received massage therapy reported lower anxiety after the massage.
      Their attitude toward asthma also improved over the study, but only one measure
      of pulmonary function (forced expiratory flow 25% to 75%) improved. The reason
      for the smaller therapeutic benefit in the older children is unknown; however, it
      appears that daily massage improves airway caliber and control of asthma.

PMID- 9602200
TI  - X-linked recessive nephrolithiasis: presentation and diagnosis in children.
AB  - We report a new X-linked recessive nephrolithiasis kindred. X-linked recessive
      nephrolithiasis is a recently described disease characterized by recurrent
      nephrolithiasis, nephrocalcinosis, and progressive renal failure, associated with
      mutations in a renal chloride channel gene, chloride channel number 5. Screening
      individuals at risk with renal ultrasonography and measurement of urinary
      excretion of low molecular weight proteins and calcium will exclude boys without
      X-linked recessive nephrolithiasis kindred and identify boys likely to have the
      disease.

PMID- 9602201
TI  - Coinheritance of alpha-thalassemia-1 and hemoglobin E/beta zero-thalassemia:
      practical implications for neonatal screening and genetic counseling.
AB  - Hemoglobin E (HbE), alpha-thalassemia, and beta-thalassemia are common among
      Southeast Asians and often occur in compound heterozygous states that complicate
      neonatal screening. We describe a kindred with alpha-thalassemia-1, HbE, and beta
      zero-thalassemia. The proband had HbE/beta zero-thalassemia, with severe anemia
      and failure to thrive. His father also had HbE/beta zero-thalassemia but had
      coinherited alpha-thalassemia-1 and was free of symptoms.

PMID- 9602202
TI  - High-versus low-dose erythropoietin in extremely low birth weight infants. The
      European Multicenter rhEPO Study Group.
AB  - OBJECTIVE: To investigate whether a weekly 1500 IU/kg dose of recombinant human
      erythropoietin (rhEPO) is more effective than a dose of 750 IU/kg/week in
      preventing anemia and reducing the transfusion need in infants with birth weights
      less than 1000 gm. STUDY DESIGN: In a randomized, double-blind, multicenter
      trial, 184 infants with birth weights between 500 and 999 gm were treated with
      either rhEPO 750 (low-dose group) or 1500 IU/kg/week (high-dose group) from day 3
      of life until 37 weeks' corrected age. RESULTS: Thirty-two percent of the infants
      in each group did not receive any transfusion during the treatment period. The
      total volume of erythrocytes received was similar in each group. The success
      rate, defined as no transfusion needed and hematocrit value 0.30 L/L or greater,
      was 27.6% in the low-dose and 29.5% in the high-dose group (p = 0.96).
      CONCLUSION: Doubling the rhEPO dose of 750 IU/kg/week is not indicated in infants
      with birth weights less than 1000 gm.

PMID- 9602203
TI  - Correction of the anemia of epidermolysis bullosa with intravenous iron and
      erythropoietin.
AB  - Severe forms of epidermolysis bullosa result in a transfusion-dependent chronic
      anemia and are fatal. The cause of the anemia is unknown. We evaluated five
      children whose anemia failed to respond to oral iron but who became transfusion
      independent after treatment with intravenous iron and human recombinant
      erythropoietin.

PMID- 9602204
TI  - Abdominal aortic aneurysm 18 years after apparent resolution of an umbilical
      catheter-associated aortic thrombosis.
AB  - A young man was found to have an abdominal aortic aneurysm 18 years after the
      apparent resolution of an umbilical artery catheter-associated aortic thrombosis.
      This report underlines the need for long-term follow-up studies of infants with
      catheter-related vascular thrombosis.

PMID- 9602205
TI  - Effect of pasteurization on long chain polyunsaturated fatty acid levels and
      enzyme activities of human milk.
AB  - Milk fatty acids, including the polyunsaturated long chain fatty acids essential
      for retinal function and brain development, are not affected by pasteurization
      (62.5 degrees C for 30 min). Milk lipases are completely destroyed by
      pasteurization, whereas amylase lost only 15% of initial activity. Thus, certain
      bioactive components are stable to pasteurization of donor milk and can benefit
      the recipient infants.

PMID- 9602206
TI  - The clinical manifestation of the kwashiorkor syndrome is related to increased
      lipid peroxidation.
AB  - Along with the onset of severe kwashiorkor symptoms, a 20-month-old child showed
      biochemical signs of markedly increased lipid peroxidation, with a decrease of
      plasma antioxidants and decreased proportions of polyunsaturated fatty acids in
      plasma and red cell phospholipids. Additionally, plasma concentrations of the
      lipid peroxidation products malondialdehyde and hexanal, as well as the urinary
      excretion of leukotriene E4, were found to be increased. All biochemical
      alterations normalized along with subsequent clinical improvement. These findings
      suggest that the extent of lipid peroxidation is strongly related to the severity
      of the kwashiorkor syndrome.

PMID- 9602207
TI  - A novel presentation of Addison disease: hypoglycemia unawareness in an
      adolescent with insulin-dependent diabetes mellitus.
AB  - A 16-year-old boy with insulin-dependent diabetes mellitus (IDDM) and a history
      of marginal glycemic control had severe hypoglycemia unawareness and a marked
      decrease in insulin requirement. His counterregulatory hormone response at the
      time of hypoglycemia suggested adrenocortical and adrenomedullary dysfunction.
      Further testing confirmed Addison disease. The patient's hypoglycemia unawareness
      was reversed by glucocorticoid replacement, although the plasma epinephrine
      response to hypoglycemia remained undetectable.

PMID- 9602208
TI  - Legg-Perthes disease in three siblings, two heterozygous and one homozygous for
      the factor V Leiden mutation.
AB  - A family is described with three-generation transmission of factor V Leiden (a
      thrombophilic mutation that causes resistance to activated protein C). Legg
      Perthes disease developed in three siblings in this family. The male proband and
      his sister were heterozygous for the mutation and had unilateral hip disease at
      age 2 years. The brother, who had bilateral hip disease, was homozygous. This
      novel family provides compelling evidence for the pathoetiologic role of familial
      thrombophilia in Legg-Perthes disease.

PMID- 9602209
TI  - House staff supervision, workload, and experience in the neonatal intensive care
      unit: results of a national survey.
AB  - One hundred fifty-nine pediatric chief residents were surveyed regarding
      characteristics of the neonatal intensive care unit rotation for house staff at
      their institution. We documented substantial interinstitution variability in
      house staff NICU rotations in terms of number of rotations, and the workload and
      supervision of house staff.

PMID- 9602210
TI  - Parathyroid adenoma after radiation in an 8-year-old boy.
AB  - We describe an 8-year-old boy who had asymptomatic hypercalcemia 4 years after
      radiotherapy involving the left orbit and lungs. A right parathyroid adenoma was
      diagnosed, and normocalcemia was achieved after its removal. Routine monitoring
      of serum calcium and phosphate levels is recommended for children after head and
      neck irradiation.

PMID- 9602211
TI  - Pemoline hepatotoxicity in children.
AB  - Pemoline hepatotoxicity ranges from asymptomatic elevations in levels of serum
      aminotransferases to fulminant liver failure. We report five cases of pemoline
      hepatotoxicity in children (four boys, one girl), including the only reported
      case resulting in orthotopic liver transplantation. We conclude that pemoline
      causes toxic liver damage in children. The severity of the damage is highly
      variable, and its onset may be late in the course of treatment. Pemoline and
      methylphenidate may act synergistically to cause liver damage. The levels of
      serum aminotransferases should be monitored throughout treatment with these
      agents.

PMID- 9602212
TI  - Isoniazid-induced pure red cell aplasia in two siblings.
AB  - Pure red cell aplasia (PRCA) is a rare complication of treatment with isoniazid
      mainly observed in adults. We report two siblings who had anemia caused by PRCA
      during administration of isoniazid. On discontinuation of isoniazid, the anemia
      resolved rapidly. PRCA should be considered as a possible cause of unexplained
      anemia during isoniazid therapy in children.

PMID- 9602213
TI  - Methotrexate-induced hypersensitivity pneumonitis in a child with juvenile
      rheumatoid arthritis.
AB  - Low-dose methotrexate, widely used for juvenile rheumatoid arthritis, has been
      reported to cause pneumonitis in adults. We report on methotrexate-induced
      hypersensitivity pneumonitis in a child with juvenile rheumatoid arthritis.
      Physicians should be aware of this rare complication.

PMID- 9602214
TI  - Successful treatment of massive acute thyroid hormone poisoning with iopanoic
      acid.
AB  - We report a toddler with massive thyroid hormone poisoning in whom the addition
      of iopanoic acid to the treatment regimen (propylthiouracil and propranolol)
      resulted in a dramatic clinical and biochemical improvement. Iopanoic acid is a
      safe and effective drug in the treatment of massive thyroid hormone poisoning in
      children.

PMID- 9602215
TI  - Pediatric imaging perspective: acute limp.

PMID- 9602216
TI  - Predictive value of neonatal brain-stem auditory evoked potential for hearing
      loss in survivors of extracorporeal membrane oxygenation.

PMID- 9602217
TI  - Restricted usage of the T-cell receptor V beta repertoire in tonsillitis in
      association with palmoplantar pustulosis.
AB  - Focal infections such as chronic tonsillitis or dental caries occasionally play a
      role in the induction or exacerbation of palmoplantar pustulosis (PPP). Arthro
      osteitis is sometimes a complication in severe cases of PPP. To study the effects
      of bacterial infection on the exacerbation of cutaneous lesions and arthralgia,
      we investigated the T-cell receptor V beta repertoire in peripheral blood
      mononuclear cells (PBMC) and tonsil tissue after tonsillectomy in 4 cases, who
      had chronic tonsillitis and a history of exacerbation of cutaneous lesions
      following a sore throat. First, serum levels of interleukin-6 (IL-6) and IL-8
      were measured before and after tonsillectomy by enzyme-linked immunosorbent assay
      (ELISA). Second, 3H-TdR incorporation was used to examine the effects of the
      culture supernatant on the PBMC of the autologous patients, other PPP patients
      without tonsillitis and normal controls. T-cell receptor V beta repertoire was
      examined by the reverse transcriptase-polymerase chain reaction method. Results
      showed that IL-8 was significantly high in the serum and abundantly released from
      tonsillar lymphocytes, which may play a role in the accumulation of neutrophils
      in lesional skin. T-cell receptors V beta 6 and 12 were preferentially expressed
      on tonsillar lymphocytes, and V beta 4, 7, 9, 17 and 18 were detected relatively
      frequently. These data suggest that restricted usage of T-cell receptor V beta
      subsets may play a crucial role in the induction of tonsillitis associated with
      PPP.

PMID- 9602218
TI  - Disruption of the vertical calcium gradient in murine epidermis by a potent
      vitamin D3 analogue, KH 1060.
AB  - The hormonal forms of vitamin D3 (1,25-dihydroxyvitamin D3 and synthetic vitamin
      D3 analogues) are potent regulators of keratinocyte growth and stimulators of
      keratinocyte differentiation. Recent experiments in vitro on cultured
      keratinocytes indicate that Ca2+ may be a second messenger mediating the effects
      related to the induction of keratinocyte differentiation by the hormonal forms of
      vitamin D3. In this study we employed the technique of ion capture cytochemistry
      to investigate the effects of a potent vitamin D3 analogue, KH 1060 (20-epi-22
      oxa-24 alpha-homo-26,27-dimethyl-1,25-dihydroxyvitamin D3), on the distribution
      of bound intracellular and extracellular calcium in murine epidermis in vitro.
      Topical treatment of the skin with KH 1060 (0.4 mmol/l) resulted in the
      development of epidermal hyperplasia and hyperkeratosis. We observed that
      epidermis treated with KH 1060 contained fewer calcium deposits in the upper
      epidermal strata (both intra- and extracellularly) than the control skin. This
      phenomenon was rapid and occurred after only a single application of KH 1060.
      Calcium distribution in the basal cell layer was not affected. We propose that
      observed reduction in the quantity of calcium deposits was caused by the release
      of sequestered calcium from the intracellular stores and cellular Ca2+ uptake,
      leading eventually to the increase in the intra-cellular concentration of ionized
      calcium. The ability of the active vitamin D3 compounds to release Ca2+ may be
      important for their activity in psoriasis.

PMID- 9602219
TI  - Comparative study of the in vitro inflammatory activity of three nickel salts on
      keratinocytes.
AB  - Nickel, the allergen of contact dermatitis, induces the in vitro production of
      inflammation markers such as intracellular adhesion molecule-1, interleukin-1 and
      tumour necrosis factor-alpha by keratinocytes. The purpose of our study was to
      compare the effect in vitro of different nickel salts on keratinocyte activation
      in order to determine whether this process depends on the nature of the salt
      used. Cultured keratinocytes were incubated with three nickel salts for 24 h in
      MCDB153 medium without hydrocortisone. Nickel gluconate, nickel sulphate and
      nickel chloride were each used at four concentrations: 5.10(-5) M, 1.10(-4) M and
      1.10 (-3) M. Keratinocyte activation was studied through the production of three
      inflammation markers: intracellular adhesion molecule-1, tumour necrosis factor
      alpha and very late antigen-3 (an integrin with increased expression during
      contact dermatitis). Marker production was detected by immunocytochemistry and
      flow cytometry. Tumour necrosis factor-alpha production and intracellular
      adhesion molecule-1 and very late antigen-3 expression increased with addition of
      the three nickel salts, becoming maximal for nickel gluconate 1.10(-4) M. In a
      subsequent experiment, zinc gluconate (an anti-inflammatory molecule) at 9
      micrograms/ml reduced the very late antigen-3 expression induced by nickel
      gluconate 1.10(-4) M. Therefore, this study enabled us to determine the
      concentration of a nickel salt (nickel gluconate) inducing optimal keratinocyte
      activation in our culture conditions and also indicated the potential interest of
      very late antigen-3 as an inflammation marker.

PMID- 9602220
TI  - Thomsen-Friedenreich and its precursor (Tn) antigen expression in normal skin and
      in benign cutaneous tumours: a marker for sebaceous differentiation.
AB  - The Thomsen-Friedenreich (T) antigen is the core disaccharide of cancer
      associated carbohydrates, whose expression allegedly correlates with the
      prognosis of some carcinomas. We studied the expression of the T antigen and its
      precursor (Tn) with monoclonal antibodies in formalin-fixed specimens of normal
      skin and various benign cutaneous tumours and inflammatory lesions (n: 105). In
      normal skin, both antigens were consistently expressed within the cytoplasm of
      mature sebocytes and rarely over the luminal surface of secretory sweat gland
      cells. All (21/21) sebaceous tumours showed strong T/Tn positivity; several
      (9/16) sweat-gland tumours were also immunoreactive, although more weakly. Pilar
      (n = 11), non-adnexal tumours (n = 45) and inflammatory lesions (n = 12) were as
      a rule unreactive. These results suggest that the T antigen is a sensitive marker
      of sebaceous differentiation that can be used for the study of adnexal skin
      tumours in routinely processed tissue specimens.

PMID- 9602221
TI  - Early detection of epidermal dust-like particles in experimentally UV-induced
      lesions in patients with photosensitivity and lupus erythematosus.
AB  - Dust-like particles, producing a specific fine-speckled, epidermo-subepidermal
      direct immunofluorescence staining pattern, have been associated mainly with
      subacute cutaneous lupus erythematosus (LE). Under experimental conditions the
      appearance of immunoglobulins along the basement membrane in ultraviolet (UV)
      light-induced lesions has been reported as a late phenomenon. In this study,
      photoprovocations with UVA and UVB light were carried out in 16 photosensitive
      patients with discoid (n = 13), subacute cutaneous (n = 2) or systemic LE (n = 1)
      and serial biopsies from UV-induced lesions were processed for direct
      immunofluorescence. A specific, fine-speckled epidermal staining was detected
      within 7 to 14 days after UV provocation in 7/16 of the patients; in the majority
      of those patients associated with anti-SSA antibodies adn discoid LE without
      systemic manifestations of their disease.

PMID- 9602222
TI  - A clinical and flow cytometric model to study remission and relapse in psoriasis.
AB  - The aim of the present study has been to analyse remission and relapse
      characteristics in psoriasis vulgaris. In 15 patients, two different psoriatic
      lesions (clinical and flow cytometric study) were treated with clobetasol
      propionate until clearance for maximally 23 days. In the clinical study only
      cleared lesions were divided into three test sectors with different post
      clearance treatment: (1) alcoholic solution under occlusion, (2) occlusion only,
      and (3) no treatment. In the flow cytometric study, biopsies were taken from the
      test lesion before clobetasol therapy (i), at clearance (ii), and at relapse from
      both visibly affected and unaffected skin (iii, iv). Epidermal proliferation,
      differentiation and inflammation were quantified by multiparameter flow
      cytometry. The clinical evaluation worked well and could discriminate between the
      different therapy modalities. After 28 days, 80% of untreated sectors showed a
      relapse. Occlusion decreased this percentage to 50%. Application of the alcoholic
      solution further decreased this percentage to 30%. The flow cytometric analysis
      demonstrated a very low proliferative activity of the basal compartment at
      clearance. This activity was higher in the visibly unaffected skin at relapse,
      whereas highest values were assessed in the affected skin at relapse.
      Interestingly, at relapse the proliferative activity in the suprabasal
      compartment of the visibly unaffected skin had increased to values identical to
      the affected skin. The present model allows standardized comparison of different
      approaches for maintenance therapy in psoriasis vulgaris. We demonstrate that
      occlusion has an inhibitory effect on the tendency to relapse after successful
      treatment with clobetasol propionate. Quantitative information on remission and
      relapse of psoriasis can be obtained by multiparameter flow cytometry.

PMID- 9602223
TI  - Colorimetric method for quantifying human Stratum corneum removed by adhesive
      tape stripping.
AB  - Tape-stripping of the skin is a useful method for removing the stratum corneum
      and obtaining more information about the function of this skill layer as the main
      barrier for skin penetration. The amount of stratum corneum removed is of
      relevance in establishing the concentration profile of chemicals within the
      stratum corneum after topical application. Weighing is the preferred method for
      measuring the amount stripped, but because it is often subject to artifacts,
      alternative methods are sought. We present a simple, colorimetric method for
      determining the amount stratum corneum removed by sequential adhesive-tape
      stripping of human skin in vivo. The method is based on quantification of the
      sodium hydroxide soluble protein fraction using a commercially available protein
      assay similar to the Lowry assay. The method is shown to be an accurate and
      reproducible alternative to weighing, also demonstrating uniform removal of
      stratum corneum layers following the very initial strips.

PMID- 9602224
TI  - Studies on mast cells and histamine release in psoriasis: the effect of
      ranitidine.
AB  - The purpose of this study was to investigate histamine and skin mast cells in
      psoriasis before and during 6 months of treatment with high-dose ranitidine.
      Sixteen psoriasis patients, presenting a mean PASI score of 15.4, were compared
      with 13 age- and sex-matched healthy controls. Resting extracellular skin levels
      of histamine and histamine release to mast cell secretagogues, as measured by the
      microdialysis technique, were increased in involved psoriasis skin compared to
      normal skin in the controls. Plasma histamine, but not basophil histamine
      release, was significantly increased in the patients. Mast cells and lymphocytes
      were significantly increased in numbers in involved versus non-involved skin in
      the patients, the lymphocytes being predominantly T-lymphocytes expressing HLA-DR
      activation. During 6 months of ranitidine treatment, mean PASI score of 15.4
      decreased to 5.8. The lymphocyte infiltration, but not mast cell numbers, was
      significantly reduced during treatment, and histamine release to mast cell
      secretagogues was normalized. These observations suggest that skin mast cells in
      active psoriasis are functionally hyperreactive. The biochemical findings
      together with the clinical effect of ranitidine indicate that histamine may be
      involved in the pathophysiology of psoriasis.

PMID- 9602225
TI  - Antiinflammatory properties of cetirizine in a human contact dermatitis model.
      Clinical evaluation of patch tests is not hampered by antihistamines.
AB  - The aim of this double-blind, placebo-controlled, randomized, cross-over pilot
      study was to assess the antiinflammatory properties of cetirizine. A group of 27
      patients with a positive patch test to an allergen consecutively received
      cetirizine 10 mg o.d. or placebo during a 14-day period, respectively. At day 11
      of each period, patch testing was performed with the allergen. The image analysis
      showed a skin reaction significantly reduced under cetirizine (p = 0.03), but the
      clinical recording and the standardized chromatometry did not show any difference
      between groups. In the cross-over analysis the results of image analysis were
      influenced by the period, but this effect disappeared after adjustment of the
      ambient temperature during the 3 days of the test. These results demonstrate that
      cetirizine has an impact on the inflammatory process in a clinical model of cell
      mediated allergic reaction, although this effect is only detected with a very
      sensitive technique. They also show that it is useless to stop antihistamines
      before patch testing, since clinical evaluation of tests is not hampered by a
      potent antihistamine. Additionally this study suggests that ambient temperature
      has an influence on the results of tests.

PMID- 9602226
TI  - Cutaneous involvement as the first manifestation in a case of T-cell
      prolymphocytic leukaemia.
AB  - Mature T-cell malignancies of extracutaneous origin are rare disorders. T-cell
      prolymphocytic leukaemia (T-PLL) is the most common form of all mature T-cell
      leukaemias in adults. Secondary skill involvement by T-PLL has been reported in
      25% of patients. A case of T-PLL which presented with cutaneous infiltration
      mimicking a cellulitis-like lesion resistant to antibiotic therapy is described.
      The diagnosis of T-PLL was subsequently fully supported by the clinical,
      laboratory and cytological findings, as well as by the immunophenotypic study of
      the skin biopsy. The present case stresses the importance of accurate evaluation
      of skin lesions in the diagnosis of some haematological conditions and gives
      additional information about T-PLL such as a previously non-reported cytogenetic
      abnormality [t(6;6)] and lack of cutaneous lymphocytic-associated antigen
      expression.

PMID- 9602227
TI  - Subbandage pressure measurements comparing a long-stretch with a short-stretch
      compression bandage.
AB  - Forty-three patients with venous leg ulcers were randomized into treatment with
      either a long- or a short-stretch compression bandage. Subbandage pressure was
      regularly measured during rest and walking for a period of up to 1 year. The long
      stretch bandage was kept on as long as possible, often up to 1 week. It
      maintained a significantly higher subbandage pressure in the upright position and
      during passive dependency as well as during walking than the short-stretch
      bandage after both 2 and 24 h. The difference between maximum and minimum
      subbandage pressures during walking did not differ between the two groups. Thus,
      in contrast to general opinion, the short-stretch bandage did not produce a
      higher peak working pressure than the long-stretch bandage. The pressure
      decreased in the supine position in both groups.

PMID- 9602228
TI  - Herpes virus-like DNA (HHV-8) in immunosuppressive therapy-related, HIV-related
      and classical Kaposi's sarcoma in Norwegian patients.
AB  - The recently discovered human herpes virus 8 (Kaposi's sarcoma-associated herpes
      virus) has been implicated in the pathogenesis of Kaposi's sarcoma. Using
      polymerase chain reaction we detected DNA sequences of this herpes virus in 11 of
      14 biopsy specimens from Kaposi's sarcoma in Norwegian patients, including the
      immunosuppressive therapy-related type (3 of 3), the HIV-related type (4 of 5),
      and the classical type (4 of 6). The results support the hypothesis of a role for
      human herpes virus 8 in all types of Kaposi's sarcoma independent of geographical
      area.

PMID- 9602229
TI  - Acrodermatitis chronica atrophicans: histopathologic findings and clinical
      correlations in 111 cases.
AB  - We studied 111 consecutive, untreated and serologically confirmed patients with
      acrodermatitis chronica atrophicans. Emphasis was on the histopathologic patterns
      of erythematous and fibrous lesions, and on an assay used to correlate
      histopathologic findings with such clinical features as fibrous nodules, ulnar
      bands and the pain reaction allodynia. There was a significant correlation
      between allodynia and signs of marked inflammation, but not between allodynia and
      neural and perineural cell infiltrates or fibrosis. Moreover, there was no
      significant correlation between serum IgG titers to Borrelia and the density of
      inflammatory cell infiltrates or the proportion of plasma cells in tissue.
      Histopathologic examination did not reveal any important differences between
      fibrous nodules, ulnar bands and sclerodermatous lesions. The histopathologic
      pattern is not diagnostic per se, but characteristic enough to alert the
      experienced pathologist.

PMID- 9602230
TI  - Interdependence of eye and hair colour, skin type and skin pigmentation in a
      Caucasian population.
AB  - Eye colour, hair colour and skin colour are important risk factors for malignant
      melanoma and non-melanoma skin cancers. There are few studies in which the
      distribution of these pigmentary factors in risk populations has been assessed.
      The purpose of this study was to investigate the prevalence of the major eye and
      hair colours and the distribution of skin types and skin pigmentation in a
      Caucasian population. In 892 Danish Caucasians, eye colour, hair colour and skin
      type were assessed and facultative and constitutive skin pigmentation were
      measured objectively using skin reflectance spectroscopy. Blue eye colour and
      blond hair colour and skin type II were the most frequent (60%, 67% and 33% of
      subjects, respectively). All four major eye colours and four major hair colours
      (with the exception of red hair colour) were found within skin types I-IV and we
      could not predict the skin type or the constitutive skin pigmentation. Skin type
      could not be taken to classify individuals reliably according to their
      facultative or constitutive skin pigmentation.

PMID- 9602231
TI  - Juvenile generalized pustular psoriasis.

PMID- 9602232
TI  - Eosinophilic pustular folliculitis induced after prolonged treatment with
      systemic corticosteroids in a patient with pustulosis palmoplantaris.

PMID- 9602233
TI  - Acute generalized exanthematous pustulosis associated with paracetamol.

PMID- 9602234
TI  - Acute generalized exanthematous pustulosis induced by amoxapine.

PMID- 9602235
TI  - Pitted keratolysis: a discussion of two cases in non-weight-bearing areas.

PMID- 9602236
TI  - Somatostatin and psoriasis.

PMID- 9602237
TI  - Pemphigus foliaceus associated with cilazapril.

PMID- 9602238
TI  - Eruptive multiple keratoacanthomas of the extremities.

PMID- 9602239
TI  - Scleroderma renal crisis in association with essential oils.

PMID- 9602240
TI  - Chronic cutaneous leishmaniasis mimicking sebopsoriasis.

PMID- 9602241
TI  - Antipruritic effect of oral cyclosporin A in essential senile pruritus.

PMID- 9602242
TI  - Dermatofibrosarcoma protuberans and basal cell carcinoma.

PMID- 9602243
TI  - Herpes zoster.

PMID- 9602244
TI  - Focal dermal hypoplasia: a case with minor clinical manifestations.

PMID- 9602245
TI  - Verrucous-crusted herpes zoster in an immunocompetent patient.

PMID- 9602246
TI  - Erythema annulare centrifugum associated with pregnancy.

PMID- 9602247
TI  - Becker's naevus of the lower limb.

PMID- 9602248
TI  - Effect of antiphospholipid antibodies on beta(2) glycoprotein I-phospholipid
      Interaction.
AB  - PROBLEM: Beta(2)glycoprotein I (beta(2)GPI) physiologically binds to negatively
      charged phospholipids (PLs) and is a natural regulator of the coagulation
      cascade. Thrombotic clinical complications and recurrent fetal loss associated
      with autoimmune antiphospholipid (aPL) antibodies are thought to be related to
      their binding to Beta(2)GPI-PL complex and interference with the physiological
      function of Beta(2)GPI. METHOD OF STUDY: To investigate the effect of aPL on
      beta(2)GPI-PL interaction, we studied the binding of biotinylated Beta(2)GPI to
      cardiolipin (CL) by enzyme-linked immunosorbent assay (ELISA) in the presence and
      absence of purified aPL immunoglobulin G (IgG) antibodies. RESULTS: Adding five
      different aPL IgG antibodies with different levels of aPL activity isolated from
      the sera of five patients with aPL-associated recurrent fetal death greatly
      increased the binding of biotinylated beta(2)GPI to CL-coated plates. The optical
      densities (ODs) were 0.635, 0.890, and 1.265 in the presence of three aPL IgG
      antibodies, compared to 0.425 in the absence of aPL IgG. In contrast, normal
      human IgG had no enhancing effect. The OD was 0.480 and 0.425, respectively. The
      enhancement of beta(2)GPI binding to CL by aPL IgG correlated with the titers of
      aPL antibodies. The use of phosphate-buffered saline with increasing salt
      concentrations as a washing buffer for the ELISA resulted in more stable binding
      of beta(2)GPI to PL in the presence of aPL IgG. CONCLUSIONS: These findings
      suggest that the binding of autoimmune aPL antibodies to beta(2)GPI-PL complex
      results in abnormally tighter interaction between beta(2)GPI and PLs, which may
      lead to physiological dysfunction of beta(2)GPI as a regulator of coagulation.

PMID- 9602249
TI  - Expression of a progelatinase activator (MT1-MMP) in human fetal membranes.
AB  - PROBLEM: The finding of MMP-2 (which degrades type IV collagen) and TIMP-2 (the
      tissue inhibitor of MMP) in fetal membranes suggests the possibility of membrane
      self-destruction as an etiology of premature rupture of fetal membranes. MMP-2 is
      activated by a membrane-bound MMP (MT1-MMP). This study was undertaken to detect
      the presence of MT1-MMP in human fetal membranes. METHOD OF STUDY: Fetal
      membranes were placed in an organ explant system and stimulated with
      lipopolysaccaride (LPS). MT1-MMP expression was studied in frozen tissues by
      reverse transcriptase (RT)-polymerase chain reaction (PCR) using primers designed
      in our laboratory. DNA sequence analysis was performed to verify the specificity
      of PCR products. In situ hybridization and immunocytochemistry were used to
      localize MT1-MMP mRNA and peptide, respectively. RESULTS: RT-PCR data indicated
      the presence of mRNA for MT1-MMP in fetal membranes. Although PCR is not
      quantitative, no differences in mRNA band intensities were noticed after LPS
      stimulation. MT1-MMP expression was constitutive throughout the culture period.
      In situ hybridization demonstrated amnion, chorionic laeve, cytotrophoblast
      cells, and the cells in the reticular and spongy layer of the extracellular
      matrix as the origin of MT1-MMP mRNA and peptide. CONCLUSIONS: This is the first
      study documenting the amniochorionic membrane as a source of MT1-MMP mRNA and
      peptide. Activation of progelatinase A requires the presence of this membrane
      associated MMP. The finding of MT1-MMP in a tissue already known to produce MMP-2
      and TIMP-2 documents the full system for activation and inhibition of this
      gelatinase. During infection, an imbalance in the expression of MT1-MMP, MMP-2
      and TIMP-2 may constitute an endogenous pathway of membrane degradation.

PMID- 9602250
TI  - Placental transport of maternal immunoglobulin G in pregnancies at risk of Rh (D)
      hemolytic disease of the newborn.
AB  - PROBLEM: The following questions were addressed: Is the placental transport of
      immunoglobulin (Ig)G, IgG1, and IgG3 diminished in pregnancies at risk of
      hemolytic disease of the newborn? Is the placental transport of IgG, IgG1, and
      IgG3 correlated with the hemoglobin concentration in the fetus and AutoAnalyzer
      (AA) quantitations of maternal anti-D? METHOD OF STUDY: IgG concentrations were
      determined retrospectively in 41 paired fetal/maternal (f/m) samples in 31 Rh (D)
      alloimmunized pregnancies. IgG1 and IgG3 concentrations were determined in those
      23 cases in which the results of fetal hemoglobin concentration and quantitations
      of maternal anti-D were available. The results were compared with values found in
      normal pregnancy and correlated with maternal anti-D AA quantitations and fetal
      hemoglobin concentrations. RESULTS: Fetal IgG, IgG1, and IgG3 concentrations, and
      the corresponding fetomaternal ratios in Rh (D) alloimmunized pregnancies,
      increased with gestational age according to the following formulas (obtained by
      simple regression): Fetal IgG = -8.846 + 0.491.gestational age (GA), (R2 =
      0.544); fetal IgG = 10.021 + 0.46.GA (R2 = 0.463); fetal IgG3 = -0.865 +
      0.039.GA, (R2 = 0.327); f/m IgG = -1.006 + 0.054.GA, (R2 = 0.557); f/m IgG1 = 
      1.876 + 0.085.GA, (R2 = 0.654); f/m IgG3 = -0.199 + 0.026.GA, (R2 = 0.146).
      CONCLUSIONS: The placental transport of IgG, IgG1, and IgG3 in women with Rh (D)
      immunizations is not diminished compared with normal pregnancy. However, AA
      quantitations of anti-D are inversely correlated with f/m IgG ratio, f/m IgG1
      ratio, and fetal IgG and IgG1 concentrations (P = 0.002, P = 0.004, P = 0.02, and
      P = 0.02 respectively). The placental transport of IgG3 is significantly higher
      in pregnancies at risk of hemolytic disease of the newborn compared with IgG3
      concentrations in normal pregnancy.

PMID- 9602251
TI  - Elevated IL-6 in midtrimester amniotic fluid is involved with the onset of
      preeclampsia.
AB  - PROBLEM: The primary defect of placental development in preeclampsia is
      speculated to occur at midtrimester gestation. Abnormal feto-maternal immune
      reactions have been considered as factors in such defective placentation. METHOD
      OF STUDY: Midtrimester amniotic fluid specimens were retrospectively identified
      as coming from gestations that later had severe preeclampsia develop, gestations
      with normal outcomes, and gestations measured for cytokines tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL-1 beta, IL-6, and IL-8). The effect of each
      cytokine on thrombomodulin levels was tested in cultured trophoblast cells.
      RESULTS: Among the measured cytokines, IL-6 and IL-8 were significantly elevated
      in the midtrimester amniotic fluid of the future preeclamptic group. Trophoblasts
      stimulated with TNF-alpha plus IL-6 had significantly decreased levels of
      cellular thrombomodulin compared to those without cytokine addition. CONCLUSIONS:
      Elevated cytokines in midtrimester amniotic fluid suggest an abnormal
      fetomaternal immune response occurring before the clinical manifestation of
      preeclampsia. Cytokine-induced suppression of thrombomodulin in trophoblasts may
      be directly involved in the pathogenesis of preeclampsia.

PMID- 9602252
TI  - Congenital toxoplasmosis: efficacy of maternal treatment with spiramycin alone.
AB  - PROBLEM: The evidence supporting an additional benefit of a combined regimen of
      pyrimethamine-sulfonamides compared with spiramycin alone in the secondary
      prevention of congenital toxoplasmosis was critically evaluated. METHOD OF STUDY:
      We reviewed the series of cases published in the English literature on
      antiparasitic treatment of acute toxoplasmosis infection in pregnancy, using
      spiramycin until fetal infection is documented, then using cycles of spiramycin
      alternated with combined pyrimethamine-sulfonamide therapy. We then compared the
      occurrence of overt disease among infected offspring (both severe, represented by
      ophthalmologic or cerebral abnormalities, and mild occurrences, represented by
      asymptomatic intracranial calcifications and retinal scars without visual
      impairment) between the published case series and our consecutive series of cases
      treated during a 10-year period (January 1986-December 1995) with spiramycin
      alone. RESULTS: The prevalence of fetal infection in our series was 7.8%
      (12/154), similar to that reported after alternated regimens (7.0%). The rate of
      overt disease among infected fetuses is not different after treatment with
      alternated regimens than after continuous antibiotic spiramycin therapy [23%
      (19/82) vs. 10% (1/10); relative risk, 2.3; 95% confidence interval, 0.4, 47.0].
      The pharmacokinetics of the drugs used may account for this finding. CONCLUSION:
      The treatment of acute toxoplasmosis in pregnancy with an alternated antibiotic
      regimen of pyrimethamine-sulfonamide is not more efficacious at preventing overt
      neonatal disease than treatment with continuous spiramycin alone.

PMID- 9602253
TI  - Altered modulation of the in vitro antibody synthesis by placental factors from
      the CBA/J x DBA/2 abortion-prone mating combination.
AB  - PROBLEM: The in vitro immunomodulating effect of placental culture supernatants
      (PSs) obtained from two H-2k x H-2d allogeneic crossbreedings, the CBA/J x DBA/2
      abortion-prone mating combination, and the reproductively normal pregnancy CBA/J
      x BALB/c crossbreeding were compared, and the influence of previous deliveries
      was evaluated. The behavior of placentae obtained from CBA/J females with two
      previous pregnancies by BALB/c males was also investigated. METHOD OF STUDY:
      Supernatants of cultures of murine placentae were added to a mouse immunoglobulin
      (Ig) G1 hybridoma culture which produced anti-dinitrophenol (anti-DNP)
      antibodies. The quantity of monoclonal antibody produced, the nature of these
      antibodies, and the proliferation of the hybridoma cells were studied. RESULTS:
      CBA/J x DBA/2 placental factors obtained from multiparous females induced a
      diminished asymmetric IgG antibody production without varying the quantity of
      antibody produced. In contrast, PSs obtained from the nonresorption-prone CBA/J x
      BALB/c mating combination with the same number of previous deliveries enhanced
      the production of both symmetric and asymmetric anti-DNP molecules and also
      increased the proportion of asymmetric blocking monoclonal antibodies (mAbs)
      synthesized by the hybridoma. Both of the PSs analyzed had induced similar
      inhibition of 3H-thymidine uptake. PSs obtained from the abortion-prone mating
      combination whose CBA/J females had two previous pregnancies by BALB/c males
      showed similar immunomodulating effects to those observed using multiparous CBA/J
      x BALB/c placentae. CONCLUSIONS: We propose that the placenta produces soluble
      factors that participate in the regulation of antibody synthesis by the mother
      during gestation. Such a placental immunomodulating effect appears to be altered
      in the CBA/J x DBA/2 abortion-prone mating combination and could be corrected by
      previous pregnancies by BALB/c males. These observations suggest that placental
      factors would be relevant to the protection of the fetus and might play an
      important role in the immune equilibrium between mother and fetus. Asymmetric
      antibody production as a Th2 responsiveness was also discussed.

PMID- 9602254
TI  - What is the role of erythropoietin in patients with solid tumours?

PMID- 9602255
TI  - The current state of the art in treating stage IIIA (N2) lung cancer.

PMID- 9602256
TI  - Does bone marrow involvement affect prognosis in small-cell lung cancer?

PMID- 9602257
TI  - One community. The B. Chevalier Lecture, held at the EORTC New Drugs Meeting,
      Lugano, Switzerland, 19-21 June 1997.

PMID- 9602258
TI  - Recombinant human erythropoietin in the treatment of chemotherapy-induced anemia
      and prevention of transfusion requirement associated with solid tumors: a
      randomized, controlled study.
AB  - BACKGROUND: Anemia is a common side effect of anticancer chemotherapy. Blood
      transfusion, previously the only available treatment for chemotherapy-induced
      anemia, may result in some clinical or subclinical adverse effects in the
      recipients. Recombinant human erythropoietin (rhEPO) provides a new treatment
      modality for chemotherapy-induced anemia. PATIENTS AND METHODS: To evaluate the
      effect of rhEPO on the need for blood transfusions and on hemoglobin (Hb)
      concentrations, 227 patients with solid tumors and chemotherapy-induced anemia
      were enrolled in a randomized, controlled, clinical trial. Of 189 patients
      evaluable for efficacy, 101 received 5000 IU rhEPO daily s.c., while 88 patients
      received no treatment during the 12-week controlled phase of the study. RESULTS:
      The results demonstrate a statistically significant reduction in the need for
      blood transfusions (28% vs. 42%, P = 0.028) and in the mean volume of packed red
      blood cells transfused (152 ml vs. 190 ml, P = 0.044) in patients treated with
      rhEPO compared to untreated controls. This effect was even more pronounced in
      patients receiving platinum-based chemotherapy (26% vs. 45%, P = 0.038). During
      the controlled treatment phase, the median Hb values increased in the rhEPO
      patients while remaining unchanged in the control group. The response was seen in
      all tumor types. CONCLUSIONS: RhEPO administration at a dose of 5000 IU daily
      s.c. increases hemoglobin levels and reduces transfusion requirements in
      chemotherapy-induced anemia, especially during platinum-based chemotherapy.

PMID- 9602259
TI  - Vindesine-ifosfamide-platinum (VIP) induction chemotherapy in surgically staged
      IIIA-N2 non-small-cell lung cancer: a prospective study. Leuven Lung Cancer
      Group.
AB  - PURPOSE: In the pioneer data from the Memorial-Sloan-Kettering group,
      preoperative mitomycin-C-vindesine-platinum (MVP) induction chemotherapy in N2
      NSCLC was accompanied with substantial pulmonary toxicity. In this study, the
      efficacy and toxicity of three-drug VIP induction chemotherapy, the pathologic
      response in resection specimens, the early survival and relapse patterns are
      examined. PATIENTS AND METHODS: Between June 1995 and March 1997, 39 consecutive
      patients with pathology proven N2-NSCLC were treated with three cycles of VIP
      induction, followed by definitive locoregional treatment (resection and
      mediastinal dissection or radical radiotherapy). Several patients had unfavorable
      prognostic characteristics with respect to clinical and biological findings,
      tumor location and bulk of disease. RESULTS: The response rate to chemotherapy
      was 59% (95% Confidence Interval 34-75). Twenty-three responding patients had
      radical locoregional treatment: radical radiotherapy in four, resection in 19.
      Downstaging was present in nine of the 19 resection specimens, with two
      pathologic complete responses. The median survival time (MST) of all patients is
      19 months, with a projected two-year survival of 49%. In patients responsive to
      chemotherapy who received definitive local treatment, the MST is not yet reached,
      and the projected two-year survival is 57%. Relapses were mainly distant, with
      isolated brain relapse as a disturbing finding. The main toxicity's were
      leukopenia and vomiting, but they were manageable. In contrast with MVP, no
      severe pulmonary toxicity occurred. CONCLUSIONS: VIP is a suitable induction
      regimen for N2-NSCLC, demonstrating a good activity and very acceptable toxicity.

PMID- 9602260
TI  - Good symptom relief with palliative MVP (mitomycin-C, vinblastine and cisplatin)
      chemotherapy in malignant mesothelioma.
AB  - PURPOSE: To evaluate the therapeutic impact of a simple combination chemotherapy
      regimen on symptoms related to malignant mesothelioma. MATERIALS AND METHODS:
      Between October 1986 and June 1997, 39 patients with advanced inoperable
      malignant mesothelioma were treated with palliative MVP (mitomycin-C 8 mg/m2 q.
      six weeks, vinblastine 6 mg/m2 q. three weeks and cisplatin 50 mg/m2 q. three
      weeks) chemotherapy and assessed for objective response and relief of symptoms.
      RESULTS: Eight of 39 patients (20%) achieved an objective partial response with a
      median duration of nine months: only five patients had progression of disease
      during chemotherapy. Twenty-four of 39 (62%) had an overall improvement in their
      symptomology with particularly good responses for pain (79%). These benefits were
      independent of performance status. Resolution of symptoms was achieved in all
      responding patients within two treatment cycles. There was no statistically
      significant difference in duration and incidence of symptom response in those
      patients achieving radiological PR compared with those with no change and more
      than 60% of patients with radiological no change obtained useful symptom control.
      The treatment was well tolerated with only four patients developing grade 3
      leucopenia and three with grade 3 nausea. CONCLUSIONS: MVP is a well tolerated
      regimen and its use in malignant mesothelioma provides useful symptomatic
      benefit. These results should be the basis for further trials of MVP in the
      management of mesothelioma with symptom control as a principal endpoint.

PMID- 9602261
TI  - Primary metastatic (stage IV) Ewing tumor: survival analysis of 171 patients from
      the EICESS studies. European Intergroup Cooperative Ewing Sarcoma Studies.
AB  - BACKGROUND: In the multicenter European Intergroup Cooperative Ewing's Sarcoma
      Studies, localized Ewing tumors of bone were treated by combination chemotherapy
      with surgery and/or radiotherapy. Patients with primary metastases (pm-pts) were
      treated in high risk protocols. PATIENTS AND METHODS: One hundred seventy-seven
      pm-pts were registered from January 1990 to December 1995, 171 were evaluable for
      survival analyses. Thirty-six pm-pts received myeloablative megatherapy with stem
      cell rescue following conventional treatment. Bilateral whole lung irradiation
      (WLI) was administered in 57 pm-pts with pulmonary involvement. Event-free
      survival (EFS) rates were estimated by Kaplan-Meier analysis. Prognostic factors
      were identified by log-rank statistics, Cox procedures and logistic regression.
      RESULTS: Eighty-nine deaths were recorded by 1 February 1997, EFS four years
      after diagnosis for all 171 pm-pts was 0.27. EFS for isolated lung metastases was
      0.34, for bone/bone marrow (BM) metastases, 0.28, and for combined lung plus
      bone/BM metastases, 0.14 (P < 0.005). WLI improved outcome in case of isolated
      pulmonary involvement (0.40 vs. 0.19, P < 0.05). In pm-pts with combined
      pulmonary/skeletal metastases, intensification by megatherapy and/or WLI improved
      EFS from 0.00 to 0.27 (P = 0.0001). CONCLUSIONS: EFS four years after diagnosis
      in patients with disseminated Ewing tumors is 0.27. Whole lung irradiation and
      megatherapy improve outcome in subgroups of patients with disseminated Ewing
      tumors is 0.27. Whole lung irradiation and megatherapy improve outcome in
      subgroups of patients with disseminated Ewing disease.

PMID- 9602262
TI  - Detection of identical Hodgkin-Reed Sternberg cell specific immunoglobulin gene
      rearrangements in a patient with Hodgkin's disease of mixed cellularity subtype
      at primary diagnosis and in relapse two and a half years later.
AB  - BACKGROUND: The malignant nature of Hodgkin-Reed Sternberg (H-RS) cells has been
      questioned due to their scarcity in lymphoma tissues. Recently, using
      micromanipulation of H-RS cells and single cell PCR evidence was obtained that H
      RS cells represent a clonal B-cell population. In these studies H-RS cells were
      isolated from each one lymph node for a given case. In classical Hodgkin's
      disease (HD) it thus could not be ruled out that H-RS cell clonality reflected a
      locally restricted clonal proliferation. We analysed biopsy specimens from a
      patient suffering from HD for the presence of clonally related H-RS cells at
      primary diagnosis and during relapse of the disease. MATERIALS AND METHODS: In
      1994 the H-RS cell line L1236 was generated from the peripheral blood of a
      patient suffering from a disseminating relapse of HD of mixed cellularity
      subtype. The patient had relapsed despite intensive treatment including high dose
      chemotherapy and autologous bone marrow transplantation. The clonal identity of
      this cell line with H-RS cells in situ was proven by amplifying identical Ig gene
      rearrangements of the cell line as well as of single H-RS cells picked from the
      patients bone marrow. Primers covering the CDR3 region were chosen from the H-RS
      cell specific VH1 gene rearrangement to detect H-RS cells of the identical clone
      by amplifying the rearranged VH1 genes in tissue samples obtained during
      disseminating relapsing disease and at primary diagnosis of HD in 1991. RESULTS:
      The H-RS cell specific DNA sequence was detected in all affected tissues analysed
      including the cervical lymph node which has been exstirpated at primary
      diagnosis. CONCLUSION: This finding indicates the existence of a clonal H-RS cell
      population during the first manifestation of HD and persistence and dissemination
      of this clone despite aggressive treatment. Thus, in the described case the
      malignant nature of H-RS cells defined by dissemination and recurrence of the
      identical H-RS cell clone in relapsing disease is proven.

PMID- 9602263
TI  - Favorable outcome of patients with relapsed or refractory Hodgkin's disease
      treated with high-dose chemotherapy and stem cell rescue at the time of maximal
      response to conventional salvage therapy (Dex-BEAM).
AB  - BACKGROUND: Disease status before high-dose chemotherapy with autologous bone
      marrow transplantation (ABMT) or peripheral blood stem cell transplantation
      (PBSCT) is an important predictor of transplantation-related toxicity and event
      free survival (EFS) for patients with relapsed or refractory Hodgkin's disease
      (HD). We performed a phase II study in patients with relapsed or refractory HD to
      evaluate the feasibility of four cycles of Dexa-BEAM followed by high-dose
      chemotherapy with ABMT or PBSCT. PATIENTS AND METHODS: Twenty-six patients
      (median age 30, range 20-40 years) were treated with 2-4 courses of
      dexamethasone, carmustine, etoposide, cytarabine and melphalan (Dexa-BEAM) as
      salvage chemotherapy in order to attain maximal response. Patients achieving
      complete response (CR) or partial response (PR) received high-dose chemotherapy
      with ABMT or PBSCT. The conditioning regimen used was CVB (cyclophosphamide,
      carmustine, etoposide). RESULTS: Eighteen patients responded to Dexa-BEAM,
      resulting in a response rate of 69%. At the time of transplant 16 patients were
      in CR two patients in PR. At present 14 patients transplanted are in continuous
      CR (median follow-up 40 months, range 14-60 months). Two patients with PR after
      four courses of Dexa-BEAM relapsed and died three months posttransplantation. Two
      patients with CR at the time of transplant relapsed after nine and 13 months
      respectively. Eight patients had rapid progressive disease after 2-4 cycles of
      Dexa-BEAM. One patient with progressive disease died in gram-negative sepsis
      after four cycles of Dexa-BEAM. There was no transplantation-related death.
      CONCLUSION: These data suggests the use of high-dose chemotherapy followed by
      stem cell transplantation at the time of maximal response.

PMID- 9602264
TI  - Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and
      acute leukemia survivors. Cancer and Leukemia Group B.
AB  - BACKGROUND: The purpose of this study was to compare the long-term psychosocial
      adaptation of Hodgkin's disease and adult acute leukemia survivors. PATIENTS AND
      METHODS: Two hundred seventy-three Hodgkin's disease (HD) and 206 adult acute
      leukemia (AL) survivors were interviewed by telephone concerning their
      psychosocial adjustment and problems they attributed to having been treated for
      cancer, using identical research procedures and a common set of instruments. The
      following measures were used: Psychosocial Adjustment to Illness Scale (PAIS);
      Brief Symptom Inventory (BSI); current Conditioned Nausea and Vomiting triggered
      by treatment-related stimuli (CNVI); Indices of Employment, Insurance and Sexual
      Problems Attributed to Cancer; Negative Socioeconomic Impact of Cancer Index
      (NSI). All participants had been treated on one of nine Hodgkin's disease or 13
      acute leukemia Cancer and Leukemia Group B (CALGB) clinical trials from 1966
      1988, and had been off treatment for one year or more (mean years: HD = 5.9; AL =
      5.6). RESULTS: HD survivors' risk of having a high distress score on the BSI was
      almost twice that found for AL survivors (odds ratio = 1.90), with 21% of HD vs.
      14% of AL survivors (P < 0.05) having scores that were 1.5 standard deviations
      above the norm, suggestive of a possible psychiatric disorder. HD survivors
      reported greater fatigue (POMS Fatigue, P = 0.01; Vigor Subscales, P = 0.001),
      greater conditioned nausea (CNVI, P < 0.05), greater impact of cancer on their
      family life (PAIS Domestic Environment, P = 0.004) and poorer sexual functioning
      (PAIS Sexual Relationships, P = 0.0001), than AL survivors. CONCLUSIONS:
      Treatment-related issues may have placed HD survivors at a greater risk for
      problems in long-term adaptation than AL survivors.

PMID- 9602265
TI  - Determination and validation of a predictive model for Clostridium difficile
      diarrhea in hospitalized oncology patients.
AB  - BACKGROUND: Clostridium difficile colitis in the cancer patient receiving
      chemotherapy is a frequent cause of morbidity which may prolong hospitalization.
      Techniques for identifying infection often delay the initiation of therapy.
      PATIENTS AND METHODS: In this retrospective case-control analysis, we identified
      predictors for C. difficile-associated diarrhea in 29 patients hospitalized from
      1988 to 1993 on a hematologic malignancy/bone marrow transplant unit (hospital
      A). We then validated our model with 58 C. difficile cases and 74 controls
      admitted to an oncology unit from a different institution (hospital B). RESULTS:
      We found that low intensity of chemotherapy (P < 0.001), lack of parenteral
      vancomycin use (P = 0.03) and hospitalization within the past two months (P =
      0.05) were independently predictive of C. difficile colitis by multivariate
      analysis. These variables were weighted for predictive capability using a
      receiver operator characteristic score; low intensity chemotherapy was assigned
      two points, lack of parenteral vancomycin received one point and prior
      hospitalization one point (P < 0.001 by chi 2 for trend). The receiver operating
      characteristic (ROC) curve areas were 0.78 for patients at hospital A and 0.70 at
      hospital B indicating moderate drop off in discrimination. Compared to hospital A
      patients, hospital B patients hospitalized between 1989 and 1994 were more often
      women (P = 0.04), received less systemic vancomycin (P = 0.01), were less
      frequently neutropenic (P < 0.05), and received less intense chemotherapy
      regimens (P < 0.05). Despite these differences in demographics in patients
      between these institutions, our predictive model was validated in hospital B
      patients (P = 0.02 by chi 2 for trend). CONCLUSIONS: The results of this study
      may help clinicians predict the risk of C. difficile disease in the hospitalized
      immunocompromised oncology patient and may help guide empiric therapy while
      awaiting results of stool toxin assays.

PMID- 9602266
TI  - DNA-topoisomerase I activity and content in epithelial ovarian cancer.
AB  - BACKGROUND: The levels and activity of topoisomerase I were determined in 35
      biopsies from patients with ovarian cancer. PATIENTS AND METHODS: The activity
      was defined by the ability to relax supercoiled DNA plasmid, and levels were
      determined by Western blotting and immunohistochemistry. RESULTS: We detected
      topoisomerase I activity in all samples, although at different levels. Enzymatic
      activity was the same in fresh and frozen tissues. Western blotting analysis
      detected topoisomerase I in 29 of 35 tumor samples but in the remaining six the
      levels were below the detection limit. We analyzed the distribution of
      topoisomerase I in tumor cells and normal infiltrating cells by
      immunohistochemistry. The enzyme was mainly associated with tumor cells although
      there were four samples in which tumor cells were negative but in which normal
      cells, mainly lymphocytes, yielded a positive result. CONCLUSIONS: The results
      indicate that topoisomerase I enzymatic activity is detectable in human ovarian
      tumors, varying among patients. No correlations were found between the levels of
      the enzyme and its activity. Because of the high heterogeneity observed,
      enzymatic activity assays should be combined with immunohistochemical evaluation
      of Topo I in the tumor and normal cells present in the tissue.

PMID- 9602267
TI  - Coincidence of seminoma and sarcoidosis: a myth or fact?
AB  - A patient with a stage II seminoma of the testis was treated with a routine
      orchidectomy and irradiation. One and a half years later enlarged mediastinal
      lymph nodes were noted. Additional staging showed no other abnormalities and a
      mediastinoscopy was performed. The initial histologic examination confirmed the
      clinically suspected diagnosis of sarcoidosis. However, additional
      immunohistochemical analysis unexpectedly demonstrated that there was also a
      microscopic relapse of the testis tumor. The literature concerning the co
      incidence of non-caseating granulomas and testis tumors is reviewed. It is not
      clear, whether the granulomas indicate the presence of genuine idiopathic
      sarcoidosis or whether they reflect a sarcoid-like reaction against tumor
      antigens. The immunopathogenesis of sarcoid formation and its possible biologic
      significance in obtaining a spontaneous tumor remission is discussed.

PMID- 9602268
TI  - Activity of paclitaxel by three-hour infusion in Asian patients with metastatic
      undifferentiated nasopharyngeal cancer.
AB  - BACKGROUND: Despite its moderate anti-tumour activity in head and neck cancers
      there have been no reports on the activity of paclitaxel in patients with
      nasopharyngeal cancer, a highly chemosensitive tumour. A phase II study was thus
      initiated to determine the objective response rate and toxicity of paclitaxel in
      patients with previously untreated metastatic nasopharyngeal cancer. PATIENTS AND
      METHODS: Twenty-four patients with previously untreated measurable metastatic
      nasopharyngeal carcinoma were accrued, one of them ineligible because of
      concomitant beta-blocker usage. Male:female ratio was 19:5, with a median age of
      46 years. All had previously received radiotherapy but were chemotherapy-naive.
      The great majority (20 of 24) had undifferentiated carcinoma. Paclitaxel
      (Anzatax, Faulding Pharmaceuticals) 175 mg/m2 was given intravenously over three
      hours every 21 days after premedication with oral dexamethasone and intravenous
      diphenhydramine and cimetidine. RESULTS: There were five (21.7%) partial
      responses while eight patients remained stable. Median response duration was 7.5
      months and median survival was 12 months. The main toxicity was haematological,
      with grade 1-2 neutropenia in 19% and grade 3-4 neutropenia in 4.5% of cycles.
      Three cycles were complicated by grade 3-4 anaemia and one patient required a
      blood transfusion. No thrombocytopenia was seen. Peripheral neuropathy was
      frequent (20 of 23 patients) but mild. Alopecia was complete in 14 patients.
      There were no cardiac toxicity or hypersensitivity reactions. CONCLUSIONS:
      Paclitaxel is well tolerated even in previously irradiated patients with
      metastatic nasopharyngeal cancer. Single-agent activity was 22% and its inclusion
      into combination chemotherapy regimens should be studied.

PMID- 9602269
TI  - First-line treatment of advanced non-small-cell lung cancer with docetaxel and
      cisplatin: a multicenter phase II study.
AB  - PURPOSE: To evaluate the efficacy and safety of the docetaxel-cisplatin
      combination in patients with advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed,
      measurable stage IIIB or IV NSCLC, a World Health Organization (WHO) performance
      status of 0-2 and adequate bone marrow, renal, hepatic and cardiac function were
      eligible for the study. Patients received docetaxel (100 mg/m2) as an one-hour
      infusion on day 1 and cisplatin (80 mg/m2) as a 30-min infusion with appropriate
      hydration on day 2. Granulocyte colony-stimulating factor (G-CSF; 150
      micrograms/m2, SC) was given on days 3 to 13. Treatment was repeated every three
      weeks. RESULTS: Fifty-three patients were enrolled (28 with stage IIIB and 25
      with stage IV). One complete and 23 partial responses were observed (overall
      response rate (OR): 45%; 95% CI: 34.1%-61.8%). The response rate was 57% and 32%
      in patients with stages IIIB and IV disease (P = NS). The median time to
      progression was 36 weeks and the median survival 48 weeks; the one-year survival
      was 48%. Grade 3-4 neutropenia occurred in 23 patients, 15 of whom were
      hospitalized for neutropenic fever; two patients died of sepsis. Grade 2
      neurotoxicity was observed in six patients and grade 3 in five patients; grade 3
      fatigue occurred in seven patients, grade 3-4 mucositis in four patients and
      grade 3-4 diarrhea in six patients. Mild allergic reactions and oedema were
      observed in five and four patients, respectively. The median dose intensity was
      30 mg/m2/week for docetaxel and 24 mg/m2/week for cisplatin, corresponding to 91%
      and 89% of the specified protocol doses, respectively. CONCLUSIONS: The docetaxel
      cisplatin combination is an active regimen in advanced NSCLC, but hematologic
      toxicity remains high despite the prophylactic use of G-CSF.

PMID- 9602270
TI  - Clinical phase II evaluation of paclitaxel in combination with cisplatin in
      metastatic or recurrent squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Paclitaxel as single agent has shown marked activity in several
      malignancies. The aim of the present phase II trial was to determine the activity
      of paclitaxel/cisplatin in patients with metastatic or recurrent squamous cell
      carcinoma of the head and neck. PATIENTS AND METHODS: 200 mg/m2 paclitaxel was
      administered over three hours followed by cisplatin (100 mg/m2), repeated every
      22 days. Twenty-eight patients were entered and received a total of 99 cycles
      (median 2, range 1-6). All patients were evaluable for toxicity, and 25 for
      response. RESULTS: Hematologic toxicities included leukopenia CTC grade 3 in 13
      patients, and grade 4 in five patients, neutropenia grade 3 in nine patients, and
      grade 4 in eight patients, grade 3 anemia and grade 2 thrombocytopenia in one
      patient each. Non-hematologic toxicities included hypotension grade 2 (six
      patients), grade 3 (four patients), and grade 4 (two patients). A decline in
      renal function was observed in 15 courses and 10 patients, leading to a median
      delay of 2.5 days. Neurosensory and neuromotor toxicity grade 1 were observed in
      13 patients (grade 2: 12 patients; grade 3: one patient), myalgia grade 3 in one
      patient, asthenia grade 3 in two and grade 4 in one patient. Partial responses
      were observed in 12 patients for an overall response rate of 48% (95% CI: 28%
      68%) with a median response duration of 6.5 months (range 1-10 months). Stable
      disease was observed in seven patients, of who two also had clinical benefit.
      CONCLUSIONS: Paclitaxel 200 mg/m2 administered over three hours combined with
      cisplatin 100 mg/m2 is an active regimen warranting further evaluation.

PMID- 9602272
TI  - Proceedings of the 5th Symposium on Bacterial Genetics and Ecology (BAGECO 5).
      Nafplion, Greece, 25-29 May 1996.

PMID- 9602271
TI  - Treatment of post-transplant lymphoproliferative disease (PTLD) following solid
      organ transplantation with low-dose chemotherapy.

PMID- 9602273
TI  - Influence of plant genotype on the selection of nodulating Sinorhizobium meliloti
      strains by Medicago sativa.
AB  - We analysed the genetic diversity of 270 Sinorhizobium meliloti strains isolated
      from nodules of three different Medicago sativa varieties, planted in three
      different Italian soils, combining the Analysis of Molecular Variance (AMOVA)
      with the Random Amplified Polymorphic DNA (RAPD) technique to estimate variance
      among RAPD patterns with the aim to draw an objective description of the
      population genetic structure. Results indicated that a general intraspecific
      genetic diversity was globally distributed among all the population, however a
      very high level of diversity was found among strains nodulating different
      Medicago sativa varieties. Moreover the distribution of the RAPD haplotypes among
      the plant varieties also showed to be non-random. The overall data indicated that
      the plant genotype is a major factor in shaping the genetic structure of this
      natural Rhizobium population.

PMID- 9602274
TI  - Broad-scale analysis of soil microbial community DNA from Upland grasslands.
AB  - We have applied a broad-scale approach to the analysis of DNA extracted from
      soils which support characteristic grasslands at an upland site in the UK. To
      test for the degree of coherence between microbial and vascular communities,
      grasslands were characterised as 'improved', 'semi-improved', or 'unimproved',
      according to the degree of management they had received and consequent botanical
      composition. Microbial DNA was extracted directly from the grassland soils and
      analysed by three techniques: (i) thermal denaturation, which profiles the
      guanine and cytosine (G + C) base distribution within the community; (ii) cross
      hybridisation of the DNA which measures the degree of similarity between the
      samples; (iii) measurement of reassociation kinetics of denatured DNA, which
      provides a measure of the complexity of the DNA. Thermal denaturation revealed
      significant differences in the %G + C composition of the communities. DNA from
      the improved soil had the highest median %G + C value, whilst that from the
      unimproved soil had the lowest. The relative distribution of G + C bases also
      differed significantly between the samples from the three grasslands. Cross
      hybridisation of DNA from the different soils also indicated significant
      differences in the degree of similarity between the DNA from the grasslands, with
      unimproved showing 59% similarity to improved. Indices from the cross
      hybridisation assay suggested that, in terms of complexity, the samples ranked
      unimproved > semi-improved > improved. Reassociation kinetics supported this
      conclusion, but the rates of reassociation were such that less than 40%
      reassociation occurred over a 31-day period, thus preventing calculation of
      C(o)t1/2.

PMID- 9602275
TI  - A review of available systems to investigate transfer of DNA to indigenous soil
      bacteria.
AB  - The deliberate or accidental release of genetically engineered microorganisms
      (GEMs) in the environment has led to some questions concerning microbial
      survival, transfer of DNA to the indigenous microflora and environmental
      consequences. Amongst horizontal gene transfer mechanisms, conjugation is
      probably the most frequent in the environment. With the aim of evaluating risks
      associated with environmental release of GEMs and their engineered DNA, studies
      of conjugative gene transfer between a donor strain and indigenous microflora
      have been conducted. Such studies required the development of a donor
      counterselection system to prevent growth of donor cells on transconjugant
      selective plates. This review summarizes the known and potential donor
      counterselection systems.

PMID- 9602276
TI  - Santa Rosalia revisited: why are there so many species of bacteria?
AB  - The diversity of bacteria in the world is very poorly known. Usually less than
      one percent of the bacteria from natural communities can be grown in the
      laboratory. This has caused us to underestimate bacterial diversity and biased
      our view of bacterial communities. The tools are now available to estimate the
      number of bacterial species in a community and to estimate the difference between
      communities. Using what data are available, I have estimated that thirty grams of
      forest soil contains over half a million species. The species difference between
      related communities suggests that the number of species of bacteria may be more
      than a thousand million. I suppose that the explanation for such a large number
      of bacterial species is simply that speciation in bacteria is easy and extinction
      difficult, giving a rate of speciation higher than the rate of extinction,
      leading to an ever increasing number of species over time. The idea that
      speciation is easy is justified from the results of recent experimental work in
      bacterial evolution.

PMID- 9602277
TI  - Evolution of competitive fitness in experimental populations of E. coli: what
      makes one genotype a better competitor than another?
AB  - An important problem in microbial ecology is to identify those phenotypic
      attributes that are responsible for competitive fitness in a particular
      environment. Thousands of papers have been published on the physiology,
      biochemistry, and molecular genetics of Escherichia coli and other bacterial
      models. Nonetheless, little is known about what makes one genotype a better
      competitor than another even in such well studied systems. Here, we review
      experiments to identify the phenotypic bases of improved competitive fitness in
      twelve E. coli populations that evolved for thousands of generations in a defined
      environment, in which glucose was the limiting substrate. After 10,000
      generations, the average fitness of the derived genotypes had increased by
      approximately 50% relative to the ancestor, based on competition experiments
      using marked strains in the same environment. The growth kinetics of the
      ancestral and derived genotypes showed that the latter have a shorter lag phase
      upon transfer into fresh medium and a higher maximum growth rate. Competition
      experiments were also performed in environments where other substrates were
      substituted for glucose. The derived genotypes are generally more fit in
      competition for those substrates that use the same mechanism of transport as
      glucose, which suggests that enhanced transport was an important target of
      natural selection in the evolutionary environment. All of the derived genotypes
      produce much larger cells than does the ancestor, even when both types are forced
      to grow at the same rate. Some but not all, of the derived genotypes also have
      greatly elevated mutation rates. Efforts are now underway to identify the genetic
      changes that underlie those phenotypic changes, especially substrate specificity
      and elevated mutation rate for which there are good candidate loci.
      Identification and subsequent manipulation of these genes may provide new
      insights into the reproducibility of adaptive evolution, the importance of co
      adapted gene complexes, and the extent to which distinct phenotypes (e.g.,
      substrate specificity and cell size) are affected by the same mutations.

PMID- 9602278
TI  - A comparative study on the frequency of prophages among natural isolates of
      Salmonella and Escherichia coli with emphasis on generalized transducers.
AB  - Several collections of natural isolates of the genus Salmonella and of the
      species Escherichia coli were studied for the release of viable temperate phages.
      The results indicated that functional prophage genomes may be a common
      constituent of all bacterial genomes of the investigated strains. About 99% of
      the Salmonella phages are capable of generalized transduction of chromosomal host
      markers and plasmids. The ratio of transducing E. coli phages is significantly
      lower.

PMID- 9602279
TI  - Sequences around the fragmentation sites of the large subunit ribosomal RNA in
      the family Rhizobiaceae. 23S-like rRNAs in Rhizobiaceae.
AB  - We demonstrated that the representatives of the family Rhizobiaceae possess,
      instead of one single 23S rRNA molecule, three different sets of 23S-like rRNA
      fragments with sizes of about: 135 b and 2.6 kb (set 1); 135 b, 400 b, and 2.2 kb
      (set 2); 135 b and two molecules of about 1.3 kb (set 3). In two of the
      fragmentations, intervening sequences--IVS I and IVS II--are involved. The IVS I
      is connected to a cleavage of the 23S rRNA primary transcript into two modules
      (135 b and 2.6 kb large). The IVS II is located at position 543 of the gene, and
      it leads to an additional processing of the 2.6 kb rRNA species into two
      molecules with sizes of about 400 b and 2.2 kb. In contrast to the IVS I, which
      is a common feature of all rhizobia, the IVS II is present in a limited number of
      strains only. The primary and secondary structures of the regions of the
      unmatured 23S rRNA transcript possessing IVS I (helix 9) and IVS II (helix 25)
      were analysed. On the basis of our analyses we propose secondary structure models
      of the parts of the matured 23S rRNA-like molecules of rhizobia corresponding to
      the helices 9 and 25. The third fragmentation of the rhizobial 23S rRNA
      represents a break in the central part of the 2.6 kb-large rRNA and it leads to
      an occurrence of two fragments with approximately equal size of about 1.3 kb. We
      have demonstrated that the central fragmentation is not connected to the presence
      of IVSs but probably to a minor change in the nucleotide sequence in the central
      part of the 2.6 rRNA.

PMID- 9602280
TI  - Transfer of plasmid RP4 in the spermosphere and rhizosphere of barley seedling.
AB  - Transfer of plasmid RP4 to indigenous bacteria in bulk soil could only be
      detected in soil with nutrient amendment. Lack of physiological active donor and
      recipient cells was apparently one of the limiting factors in un-amended bulk
      soil. Plasmid transfer was detected both in the spermosphere and rhizosphere of
      barley seedlings. Transfer occurred from seed coated donor bacteria (i) to
      introduced recipient bacteria and (ii) to indigenous bacteria present in soil.
      Plasmid transfer was also detected from donor bacteria introduced to the soil to
      seed coated recipient bacteria. Transfer efficiencies in the rhizosphere were
      significantly below the transfer efficiencies obtained in the spermosphere. The
      transfer efficiencies detected in the barley spermosphere were among the highest
      reported from any natural environment.

PMID- 9602281
TI  - Carbon dioxide as a regulator of gene expression in microorganisms.
AB  - CO2 regulates gene expression across a diverse group of microorganisms including
      fungi, and both photosynthetic and non photosynthetic bacteria. The processes
      that CO2 regulates are diverse. Several CO2-responsive random promoter lacZ
      fusions of unknown function have been isolated from a marine Synechococcus and a
      Pseudoalteromonas sp., highlighting the wide effect of CO2 control in these
      organisms. Regulatory proteins have been described that mediate the CO2 response
      at transcription level in Bacillus anthracis, the group A streptococci and two
      Rhodobacter spp. These regulatory proteins include: AcpA and AtxA that are
      involved in CO2 control of B. anthracis capsule and toxin production; Mga that
      regulates surface associated virulence factors in the group A streptococci; and
      RegB/A, a two component signal transduction system that responds to environmental
      stimuli including CO2, to regulate photosynthetic apparatus and CO2 fixation
      enzyme synthesis in Rhodobacter spp.

PMID- 9602282
TI  - Enhancement of 2,4-dichlorophenoxyacetic acid (2,4-D) degradation in soil by
      dissemination of catabolic plasmids.
AB  - Few studies have been done to evaluate the transfer of catabolic plasmids from an
      introduced donor strain to indigenous microbial populations as a means to
      remediate contaminated soils. In this work we determined the effect of the
      conjugative transfer of two 2,4-D degradative plasmids to indigenous soil
      bacterial populations on the rate of 2,4-D degradation in soil. We also assessed
      the influence of the presence of 2,4-D on the number of transconjugants formed.
      The two plasmids used, pEMT1k and pEMT3k, encode 2,4-D degradative genes (tfd)
      that differ in DNA sequence as well as gene organisation, and confer different
      growth rates to Ralstonia eutropha JMP228 when grown with 2,4-D as a sole carbon
      source. In an agricultural soil (Ardoyen) treated with 2,4-D (100 ppm) there were
      ca. 10(7) CFU of transconjugants per gram bearing pEMT1k as well as a high number
      of pEMT3k bearing transconjugants (ca 10(6) CFU/g). In this soil the formation of
      a high number of 2,4-D degrading transconjugants resulted in faster degradation
      of 2,4-D as compared to the uninoculated control soil. In contrast, only
      transconjugants with pEMT1k were detected (at a level of ca. 10(3) CFU/g soil) in
      the untreated Ardoyen soil. High numbers of transconjugants that carried pEMT1k
      were also found in a second experiment done using forest soil (Lembeke) treated
      with 100 ppm 2,4-D. However, unlike in the Ardoyen soil, no transconjugants with
      pEMT3k were detected and the transfer of plasmid pEMT1k to indigenous bacteria
      did not result in a higher rate of decrease of 2,4-D. This may be because 2,4-D
      was readily metabolised by indigenous bacteria in this soil. The results indicate
      that bioaugmentation with catabolic plasmids may be a viable means to enhance the
      bioremediation of soils which lack an adequate intrinsic ability to degrade a
      given xenobiotic.

PMID- 9602283
TI  - Effect of fermented milk intake on plasmid transfer and on the persistence of
      transconjugants in the digestive tract of gnotobiotic mice.
AB  - Plasmid transfer occurs in the digestive tract and the transconjugants may become
      durably established. The aim of the present work is to investigate the effect of
      probiotics of plasmid transfer and on establishment of transconjugants in the
      gut. Plasmid transfers were carried out in the digestive tract of germ free mice
      associated with an E. coli K12 donor strain harboring three plasmids (R388, self
      transmissible, pCE325 and pUB2380, mobilisable,) and an E. coli recipient strain,
      PG1, of human origin (Duval-Iflah et al., 1994). Milks fermented with either
      Lactobacillus bulgaricus or Streptococcus thermophilus or symbiosis, S85, of both
      strains were given daily as 1/3 of food diet. Fermented milks have no effect on
      the transfer of R388 and pUB2380 except a slight increase of TC(R388) with milk
      fermented with S85. Long term ingestion of milk fermented with S85 inhibited the
      formation and the establishment of transconjugants TC(pCE325). Milk fermented
      with L. bulgaricus lowered the population density of TC(pCE325) in animals where
      they were already established. This phenomenon was reversible, since the density
      of TC(pCE325) increased in the same animals after cessation of supplementation.
      Bacterial cultures obtained in MRS broth and given in state of drinking water
      were compared with fermented milks. Bacterial cultures with L. bulgaricus and
      with S85 favoured the establishment of TC(pCE325). There results indicate for the
      first time that probiotics have various effects on the formation and/or
      establishment of transconjugants in the gut of axenic mice. The effects depend on
      whether the probiotics were cultivated in milk or in MRS, indicating that
      bacterial metabolites and viable bacteria can be involved.

PMID- 9602284
TI  - Survival, metabolic activity and conjugative interactions of indigenous and
      introduced streptomycete strains in soil microcosms.
AB  - The growth and activity of introduced (S. lividans TK24 pIJ673 and S. lividans
      TK23) and indigenous (S. griseus CAG17) streptomycete strains in soil was
      studied, under controlled conditions. The effect of environmental parameters such
      as temperature, soil water content and nutrient availability on the growth and
      activity of these strains, was studied using a highly dynamic fed-batch soil
      microcosm system. Using this new system, repeated cycles of active streptomycete
      growth were achieved, allowing long-term investigation of metabolic activity,
      plasmid stability and conjugative plasmid transfer. In long-term experiments,
      respiration rates and enzyme activity patterns matched the pattern of
      germination/sporulation cycles of the inoculants. In situ hybridisation, using
      fluorescently labelled oligonucleotides, also proved the presence of
      metabolically active streptomycete mycelia in sterile soil. Plasmid stability
      under varying temperatures and selective pressure was studied using the above
      system. In both sterile and non sterile amended antibiotic containing soil, no
      intraspecific transfer of plasmid pIJ673 from S. lividans TK24 to S. griseus
      CAG17 was detected. The soil microcosm system used, though, permitted detection
      of intraspecific conjugative transfer of this plasmid from S. lividans TK24 to S.
      lividans TK23 in soil.

PMID- 9602285
TI  - Origin and evolution of plasmids.
AB  - Studies on the origin and evolution of plasmids may provide valuable insights on
      the promiscuous nature of DNA. The first examples of the selfish nature of
      nucleic acids are exemplified by primordial oligoribonucleotides which evolved
      into primitive replicons. The propagation of these molecules were likely
      patterned after the current viral RNA ribozymes, which have been recently shown
      to possess RNA synthesizing and template mediated polymerizing capabilities in
      the absence of proteins. The parasitic nature of nucleic acids is depicted by
      satellite nucleic acid molecules associated with viruses. The satellite of
      adenovirus and tobacco ringspot virus serve as established examples: they contain
      no open reading frames. Comparative analysis of the replication origins of
      virions and plasmids show them to be conserved, originating from the simplest
      autocatalytic replicon to highly complex and evolved plasmids, replicating by a
      rolling circle mechanism. The eventual association of proteins with nucleic acids
      provided added efficiency and protective advantages for molecular perpetuation.
      The promiscuous and selfish nature of plasmids is demonstrated by their ability
      to genetically engineer their host so that the host cell is best able to cope and
      survive in hostile environments. Survival of the host ensures survival of the
      plasmid. Sequestering of genes by plasmids occurs when the environmental
      conditions negatively affect the host. The sequestering mechanism is fundamental
      and forms the outreach mechanisms to generate and propagate macromolecules of
      increasing size when necessary for survival. The level of sophistication of
      plasmids increases with the addition of new genes such as those that allow the
      host to occupy a specific environment normally inhospitable to the host cell. The
      vast range of plasmid types which have obtained genes interchangeably reflect the
      levels of sophistication achieved by these macromolecules. The Ti plasmid in
      Agrobacterium tumefaciens and the pSym and accessory plasmids in Rhizobium
      illustrate the level of complexity attained by replicons.

PMID- 9602286
TI  - Application of denaturing gradient gel electrophoresis (DGGE) and temperature
      gradient gel electrophoresis (TGGE) in microbial ecology.
AB  - Here, the state of the art of the application of denaturing gradient gel
      electrophoresis (DGGE) and temperature gradient gel electrophoresis (TGGE) in
      microbial ecology will be presented. Furthermore, the potentials and limitations
      of these techniques will be discussed, and it will be indicated why their use in
      ecological studies has become so important.

PMID- 9602288
TI  - Binding properties of streptococcal glucosyltransferases for hydroxyapatite,
      saliva-coated hydroxyapatite, and bacterial surfaces.
AB  - The binding specificities of Streptococcus glucosyltransferase (Gtf) B, C and D
      for hydroxyapatite (HA), saliva-coated hydroxyapatite (SHA), and bacterial
      surfaces were examined. For HA beads the following values were obtained: (K =
      affinity; N = number of binding sites) GtfB, K = 46 x 10(5) ml/mumol, N = 0.65 x
      10(-6) mumol/m2; GtfC, K = 86 x 10(5) ml/mumol, N = 4.42 x 10(-6) mumol/m2.;
      GtfD, K = 100 x 10(5) ml/mumol, N = 0.83 x 10(-6) mumol/m2. For SHA beads, the
      following values were obtained: GtfB, K = 14.7 x 10(5) ml/mumol, N = 1.03 x 10(
      6) mumol/m2; GtfC, K = 21.3 x 10(5) ml/mumol, N = 3.66 x 10(-6) mumol/m2; GtfD, K
      = 1.73 x 10(5) ml/mumol, N = 8.88 x 10(-6) mumol/m2. The binding of GtfB to SHA
      beads was reduced in the presence of parotid saliva, but the binding of GtfC and
      D was unaffected. The binding of GtfB to SHA in the presence of parotid saliva
      supplemented with GtfC and D was reduced when compared with its binding to SHA in
      the presence of parotid saliva alone. In contrast, te binding of GtfC and SHA was
      unaffected when parotid saliva was supplemented with the other Gtf enzymes. GtfB
      bound to several bacterial strains (Strep, mutans GS-5, Actinomyces viscosus
      OMZ105E and Lactobacillus casei 4646) in an active form, while GtfC and D did not
      bind to bacterial surfaces. It is concluded that of the three Gtf enzymes, GtfC
      has the highest affinity for HA and SHA surfaces and can adsorb on the the SHA
      surface in the presence of the other two enzymes. GtfD also binds to SHA in the
      presence of the other enzymes but has a very low affinity for the surface. GtfB
      does not bind to SHA in the presence of the other Gtf enzymes but binds avidly to
      bacterial surfaces in an active form. Therefore, GtfC most probably binds to
      apatitic surfaces, while GtfB binds to bacterial surfaces.

PMID- 9602287
TI  - Factors affecting the resting pH of in vitro human microcosm dental plaque and
      Streptococcus mutans biofilms.
AB  - The aim was to examine factors that potentially control the resting pH, defined
      as the pH unaffected by meals, of microcosm dental plaques and Streptococcus
      mutans biofilms under standard conditions, and to examine the effect of supplying
      urea at concentrations found intraorally. Microcosm plaques were cultured from
      plaque bacteria-enriched saliva in an 'artificial mouth' with a continuous supply
      of a medium including 0.25% mucin [Basal Medium Mucin, (BMM), 3.6 ml/hr per
      plaque] and a periodic supply of sucrose. The steady-state resting pH was 6.4
      (range +/- 0.1) in BMM containing no urea and supplied at the standard flowrate.
      This is a robust property of the ecosystem. In one experiment with a replicated
      (n = 9) set of measurements, the resting pH was approx. pH 6.3, 6.4, 6.7 and 7.3
      with 0, 1, 5 and 20 mmol/l urea in the BMM. The magnitude of sucrose- and urea
      induced pH responses was unaffected by elevating the resting pH to produce
      parallel pH curves. The sucrose-induced pH curves were analogous to those
      classically reported by Stephan that showed an association between caries
      activity and increasingly acidic plaque pH responses to glucose. Stopping the BMM
      flow caused a pH rise, indicating continuing net alkali generation from BMM
      components in the absence of a fluid flow. Step. mutans monoculture biofilms had
      an acidic resting pH of 5.0 to 5.3, which increased to 6.8 following an
      adventitious superinfection by Bacillus cereus. It was concluded that the resting
      pH in plaque results from a delicate balance between alkali and acid generation,
      which is in turn dependent both on the bacterial composition of the plaque and on
      the supply of substrates and buffers from, and metabolite clearance into, flowing
      oral fluid. In vivo the resting pH will vary with site-specific changing saliva
      flows. Urea continuously supplied at concentrations normal for saliva and
      gingival crevicular fluid can raise the resting pH of microcosm plaque by an
      amount tat in vivo would probably be significant in reducing dental caries.

PMID- 9602289
TI  - A scanning electron-microscopic study of developing human deciduous enamel on the
      dependence of the outline of surface pits on the angle of observation.
AB  - On the developing enamel surfaces of fetal human deciduous teeth, many of the
      surface pits were arcade-shaped with the arcade preferentially pointing in a
      cervical direction. The configuration of the interprism ridges between the pits
      contributed to this appearance. Surface cracks allowed verification of an incisal
      inclination of the subsurface prisms. This apparent paradox was solved when the
      specimens were tilted so that the pits were viewed in the directions of the
      prisms, giving the pits a compressed arcade-shape with the arcades pointing
      incisally. It is recommended that care should be exercised and due attention paid
      to the angle of observation when determining the orientation of pit arcades. Pit
      entry direction seems to be a more reliable feature for inferring the direction
      of tangential ameloblast movement.

PMID- 9602290
TI  - Immunocytochemical expression of type I and type II collagens by rat Meckel's
      chondrocytes in culture during phenotypic transformation.
AB  - In culture, chondrocytes of Meckel's cartilage can differentiate further to
      become bone-type collagen-synthesizing cells. Here, the replacement of type II
      collagen by type I collagen, accompanying expression of the osteocytic phenotype,
      was analysed by double immunofluorescence staining, histochemistry and electron
      microscopy. After 1 week in culture, formation of a toluidine blue-positive
      matrix, demonstrating the synthesis of cartilaginous proteoglycans, and the
      expression of type II collagen were detected. After 2 weeks, immunoreactivity
      specific for type II collagen was detected along the cartilaginous areas of the
      nodules, and type I collagen appeared in association with the immunopositive
      extracellular matrix around spindle-shaped cells. Electron microscopy revealed
      that the extracellular matrix at this stage was composed of homogeneous fine
      fibrils of type II collagen and thick cross-banded bundles of type I collagen:
      there was also continuity between the type I and II collagens. Double
      immunofluorescence staining of 3 week-old cultures revealed that type II collagen
      had been replaced by type I which was synthesized by small round cells that
      appeared at the top of the nodules. With further passage of time in culture, the
      distribution of type I collagen expanded further towards the peripheral areas
      from the central areas of the nodules. The present combination of ultrastructural
      analysis and double immunofluorescence staining shows that the transition from
      synthesis of cartilage-specific type II collagen to expression of type I collagen
      occurred sequentially in spindle-shaped cells located at the top of nodules in
      conjunction with the further differentiation of Meckel's cartilage cells.

PMID- 9602291
TI  - The effects of thermal and mechanical stimulation on blood flow in healthy and
      inflamed gingiva in man.
AB  - The purpose of this study was to compare the state of the microcirculation in
      healthy gingiva with that in untreated, inflamed gingiva in humans. Reflection
      photoplethysmography (RP) was used to record blood flow from 13 clinically
      healthy, attached gingival sites in seven adults and 11 inflamed sites in seven
      patients. Changes in the pulse amplitude of the RP signal were measured before
      and after application of thermal (cold and hot water) and mechanical (brushing)
      stimuli to the gingiva. Hot water and brushing, but not cold water, produced a
      significant increase in the pulse amplitude in healthy gingiva (p < 0.05,
      Friedman analysis and Student-Newman Keuls test). None of the stimuli produced a
      significant change in inflamed gingiva. In neither group of participants was
      there a significant correlation (Spearman rank correlation coefficient) between
      vascular responsiveness and age. The results indicated that vasomotor control may
      be impaired in inflamed gingiva.

PMID- 9602292
TI  - Effects on non-human primate mastication of reversible inactivation by cooling of
      the face primary somatosensory cortex.
AB  - Rhythmical jaw movements can be evoked by intracortical microstimulation within
      four physiologically defined regions, one of which is the primary face
      somatosensory cortex (face SI). It has been proposed that these regions may be
      involved in the selection and/or control of masticatory patterns generated at the
      brainstem level. The aim here was to determine if mastication is affected by
      reversible, cooling-induced inactivation of the face SI. Two cranial chambers
      were chronically implanted in two monkeys (Macaca fascicularis) to allow access
      bilaterally to the face SI. A thermode was placed on the dura or pia overlying
      each SI that had been shown with micro-electrode recordings to receive intraoral
      inputs. A hot or cold alcohol-water solution was pumped through the thermodes
      while the monkey chewed a small piece of apple or a sultana during precool
      (thermode temperature, 37 degree C), cool (2-4 degrees C), and postcool (37
      degrees C) conditions. Electromyographic (EMG) activity was recorded
      intramuscularly from the masseter, genioglossus, and anterior digastric. Cooling
      of SI impaired rhythmical jaw and tongue movements and EMG activity associated
      with mastication in one monkey (H5), and modified the pattern of EMG activity in
      the other (H6). The total masticatory time (i.e., time taken for chewing and
      manipulation of the bolus before swallowing) was increased. This was due
      principally to an increase in the oral transport time (i.e., time taken for
      manipulation of bolus after chewing and before swallowing: monkey H6, control,
      2.7 sec; cool, 5.2 sec, p < 0.05); the bolus was manipulated by the tongue during
      this period before swallowing. Within the chewing time (i.e., time during which
      chewing occurred), cooling resulted in a significant increase in anterior
      digastric muscle duration, a significant delay in the onset of masseter EMG
      activity, and a significant increase in the variance of genioglossus EMG
      duration. The data support the view that the face SI plays a part in modulating
      the central pattern generator for mastication.

PMID- 9602293
TI  - Induction of apoptotic cell death by photodynamic therapy in human keratinocytes.
AB  - The use of photodynamic therapy (PDT) for the treatment of skin and oral cancer
      has been the subject of several clinical studies but there has been little
      scientific evaluation of its mechanism of action. Evidence to date suggests that
      whilst epithelial cell death may be secondary to vascular damage, direct cell
      killing may occur and may involve an apoptosis-like mechanism. To investigate the
      mechanism of epithelial cell death following PDT, two cell lines, human epidermal
      keratinocytes (UP) and oral squamous cell carcinoma-derived cells (H376) were
      subjected to PDT with aluminium disulphonated phthalocyanine (AlS2Pc) as the
      photosensitizer and red laser light at 675 nm. Control groups received red laser
      light, photosensitizer or neither. The effects of PDT were assessed using an MTS
      cell-proliferation assay, which showed a significant reduction in viability (p <
      0.01) for PDT-treated cells compared to controls. For morphological analysis,
      cells were stained with haemotoxylin and eosin and the numbers showing typical
      apoptotic features counted. The treated cultures showed significantly increased
      numbers of apoptotic cells. Moreover, the H376 control cultures showed a baseline
      level of apoptosis of approx. 15%. Apoptosis was confirmed by ultrastructural
      analysis and by in situ end-labeling of DNA fragments. The results show that PDT
      using AlS2Pc as a photosensitizer promotes apoptotic cell death in UP and H376
      cells in vitro and suggest that direct killing of epithelial cells may contribute
      to tumour necrosis in vivo.

PMID- 9602294
TI  - Stimulated salivary flow rate and composition in asthmatic and non-asthmatic
      adults.
AB  - The number of decayed, missed and filled permanent teeth (DMFT), the degree of
      periodontal inflammation (Periodontal Status Index, PSI), stimulated salivary
      flow rate and the concentrations of total protein, lactoferrin, lysozyme,
      myeloperoxidase, salivary peroxidase, calcium, potassium, sodium and thiocyanate
      in whole saliva of 26 adult asthma patients were compared with those of 33 non
      asthmatic controls. The saliva was also analysed for mutans streptococci,
      lactobacilli, total anaerobic flora and Candida spp. The mean PSI (p < 0.05; 95%
      confidence interval for the difference between means (95% CI) 2.47-25.30) was
      higher and the mean stimulated salivary flow rate (p < or = 0.05; 95% CI 0.57
      0.55) was lower in the asthmatic group than in the control group. No differences
      were found between the groups in non-immune defense factors, except for
      myeloperoxidase. The myeloperoxidase concentrations were higher in asthmatics
      than in non-asthmatics (p < 0.05; 95% CI 4.4-134.0 ng/ml). No differences in
      microbial counts were found. It was concluded that stimulated salivary flow rates
      decrease while myeloperoxidase concentrations increase in adult asthmatic
      patients compared with non-asthmatic adults. The higher concentrations of
      myeloperoxidase are explained by a higher PSI in asthmatics.

PMID- 9602295
TI  - The influence of xylitol and fluoride on dental erosion in vitro.
AB  - The aim was to determine the effect of xylitol, fluoride and xylitol/fluoride
      combined on the erosion of dental enamel by pure orange juice in vitro. Freshly
      extracted bovine incisors were sectioned vertically into four equal portions.
      Each portion was then coated with an acid-resistant nail varnish except for an
      enamel window on the labial surface of the tooth. These were then divided into
      four groups with each group containing one portion of each tooth selected
      randomly. Four erosive agents were prepared as follows: (A) pure orange juice
      only; pure orange juice plus either (B) xylitol (25% w/v) or (C) fluoride (0.5
      parts/10(6)) or D) xylitol/fluoride (25% and 0.5 parts/10(6) respectively). Each
      group was assigned to one of the erosive agents and immersed six times daily for
      a period of 5 min on each occasion and stored in artificial saliva between
      exposures and for 12 hr overnight, for 24 days making a total of 12 hr of
      exposure to the assigned erosive agent. Sections were cut from each enamel
      specimen ground to a thickness of 80 microns and microradiographed. Mineral loss
      was quantified by a two-step image analysis. Mineral loss was significantly lower
      (p < 0.05) in group D (xylitol/fluoride) only when compared with group A (pure
      orange juice only). The numerical values of mineral loss could be ranked as
      follows: group D < group C < group B < group A. It was concluded that xylitol and
      fluoride have an additive effect in the reduction of dental erosion by pure
      orange juice in vitro.

PMID- 9602296
TI  - In vivo effect of interleukin-1 alpha on colony-stimulating factor-1 gene
      expression in the dental follicle of the rat molar.
AB  - Interleukin-1 alpha (IL-1 alpha) acts in vitro to enhance the gene expression of
      colony-stimulating factor-1 (CSF-1) of dental follicle cells. Because the dental
      follicle is required for tooth eruption and because CSF-1 appears to be a key
      molecule in initiating eruption, it was the aim of this study to determine if IL
      1 alpha could enhance the expression of the CSF-1 gene in the dental follicle in
      vivo. To determine this, rats were injected with IL-1 alpha at different ages
      postnatally and the total RNA was isolated from the dental follicles of the first
      mandibular molars. Reverse transcription-polymerase chain reaction showed that IL
      1 alpha enhanced the expression of CSF-1 in the follicle. Thus, IL-1 alpha may
      play a part in the cascade of molecular signals that initiate eruption by its
      effect upon the CSF-1 gene.

PMID- 9602298
TI  - Immunological techniques. Lymphocyte development.

PMID- 9602297
TI  - NADPH-diaphorase activity in nerves and Schwann cells in the periodontal ligament
      of rat incisor teeth.
AB  - The lingual portion of the incisor periodontal ligament demonstrated activity for
      nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase. Schwann cells
      surrounding Ruffini-like endings coexpressed NADPH-diaphorase activity and
      immunoreactivity for inducible nitric oxide synthase. NADPH-diaphorase-positive
      nerve fibres which coexpressed immunoreactivity for neuronal nitric oxide
      synthase were in contact with Schwann cells surrounding Ruffini-like endings or
      terminated as free nerve endings. Neural NADPH-diaphorase activity could not be
      found in the tissues covering the labial portion of incisor tooth root. It is
      possible that nitric oxide in Schwann cells and nerves has functions specific to
      the incisor periodontal ligament.

PMID- 9602299
TI  - Application of differential cDNA screening techniques to the identification of
      unique gene expression in tumours and lymphocytes.
AB  - Development, differentiation and cell death in all organisms are mediated by
      tightly regulated programs of differential gene expression. Furthermore, changes
      in gene expression profiles are responsible for tumour formation and tumour
      progression, as well as for many other human diseases. Thus, the definition of
      distinct patterns of gene expression is not only essential for understanding
      complex biological processes but also leads to the identification of novel
      targets for therapy of various diseases.

PMID- 9602300
TI  - The yeast two-hybrid screening technique and its use in the study of protein
      protein interactions in apoptosis.
AB  - The yeast two-hybrid technique provides a general approach for cloning cDNAs
      merely by exploiting the ability of their encoded proteins to bind to a protein
      of interest. The technique therefore offered a useful access to the analysis of
      the mechanisms of cell death at the initial stage of their study, when only a few
      of the proteins involved and very little about their mode of action were known.
      Conversely, the knowledge of cell death mechanisms gained by this technique
      provided a useful insight into both the potential and the limitations of this
      technique.

PMID- 9602301
TI  - Reading within the lines: naturally processed peptides displayed by MHC class I
      molecules.
AB  - A typical mammalian cell contains tens of thousands of different gene products.
      Snippets of this genetic information are displayed on the cell surface by MHC
      class I molecules as short peptides for immune surveillance by CD8+ T
      lymphocytes. Genetic and biochemical analysis of these peptides is revealing
      novel sources and mechanisms by which these peptide/MHC class I complexes arise.

PMID- 9602302
TI  - Exploring the mechanisms of antigen processing by cell fractionation.
AB  - It is becoming increasingly clear that most of the intracellular compartments
      that contain MHC class II products in antigen-presenting cells simply represent
      the conventional endosomes and lysosomes that are expressed in all cell types.
      Data from recent cell fractionation studies, however, predominantly those using
      electrophoresis techniques, show that a population of class-II-containing
      vesicles exists that may comprise a class of endosomes that are specialized for
      antigen processing. Strong support for this possibility comes from the
      observation that such specialized structures, designated class II vesicles
      (CIIV), are particularly abundant in mature dendritic cells.

PMID- 9602303
TI  - Lymphocyte development. The (knock-) ins and outs of lymphoid development.

PMID- 9602304
TI  - Transcriptional regulation of B-cell differentiation.
AB  - Transcription factors influence B cell differentiation by regulating the
      expression of numerous lineage-specific genes. Recent studies have identified
      factors that regulate differentiation of hematopoietic stem cells into B cell
      progenitors (PU.1 and lkaros), and further differentiation of these progenitors
      into mature B cells (NF kappa B, E2A, early B cell factor [EBF] and B cell
      specific activator protein [BSAP]). In addition, these studies demonstrate that
      complex interactions and redundancies among transcription factors safeguard the
      precise patterns of gene expression required for normal B cell differentiation.

PMID- 9602305
TI  - Transcriptional control during T-cell development.
AB  - During the past few years, the essential role of distinct transcription factors
      in specifying cell-fate decisions in a stepwise fashion during T-cell
      differentiation has been revealed. One striking feature is that a single factor
      can act at several sites throughout T-cell development, possibly through
      interactions with different partners. The challenge is now to understand how
      these interactions can account for the co-ordination of complex extracellular
      signals and gene expression programs, such as those involved in T-cell receptor
      gene recombination and expression.

PMID- 9602306
TI  - Antigen receptor gene rearrangement.
AB  - Two specialized forms of site-directed double-strand (ds) DNA breakage and
      rejoining are part of the physiologic program of lymphocytes. One is
      recombination of the V, D and J gene sequences, termed V(D)J recombination,
      occurring during early B- and T-cell development, and the other is class-switch
      recombination occurring exclusively in mature B cells. For V(D)J recombination
      significant progress has been made recently elucidating the biochemistry of the
      reaction. In particular our understanding of how DNA ds breaks are both generated
      and rejoined has increased. For class-switch recombination no definitive
      information is known about the nucleases required for making the ds breaks, but
      recent evidence suggests that the joining phase shares activities also required
      for V(D)J recombination and general DNA ds break repair.

PMID- 9602307
TI  - The alpha beta versus gamma delta T-cell lineage choice.
AB  - During thymic development, immature T cells rearrange and express the genes
      encoding the T-cell antigen receptor and mature as either alpha beta or gamma
      delta lineage T cells. In the past year, advances have been made in understanding
      the role of individual components of the T-cell antigen receptor complex in the
      development of alpha beta and gamma delta lineage T cells. In addition, the
      transmembrane receptor Notch has recently been implicated as a new player in
      alpha beta versus gamma delta lineage determination.

PMID- 9602308
TI  - B-cell lymphopoiesis in mouse and man.
AB  - Functional immunoglobulin gene rearrangement is a sine qua non for successful B
      cell development in mammalian bone marrow, but other factors are also important.
      Studies reported during the past year have contributed new insight into the
      surface receptor complexes and signaling outcomes that influence the fate of B
      cell precursors. Identification and characterization of secreted and membrane
      associated stromal cell products, and their actions on B-cell precursors, was a
      parallel area of ongoing investigation.

PMID- 9602310
TI  - Receptor editing and commitment in B lymphocytes.
AB  - B cells that fail to pass a developmental checkpoint, either as immature or
      mature B cells, can be rescued by creating a new B cell antigen receptor through
      nested secondary immunoglobulin gene rearrangements, a process termed receptor
      editing. Tolerance-mediated receptor editing occurs in self-reactive immature
      bone marrow B cells, while peripheral receptor editing probably occurs in low
      affinity B cells competing for antigen and for survival signals within the
      germinal center response.

PMID- 9602309
TI  - In vivo roles of receptor tyrosine kinases and cytokine receptors in early
      thymocyte development.
AB  - The early phases of T-cell development require both cell-cell interactions and
      soluble factors provided by stromal cells within the thymic microenvironment.
      Still, the precise nature of the signals delivered in vivo by cytokines
      (resulting in survival, proliferation or differentiation) remains unclear. Recent
      studies using mice deficient in cytokines or in their receptors have helped to
      identify essential signaling pathways required for the development of intrathymic
      precursors to mature alpha beta and gamma delta T cells. In addition, cytokine
      requirements for the development of natural killer cells were revealed in such
      mutants. The results obtained demonstrate that the development of all classes of
      lymphocytes (natural killer, gamma delta T cells and alpha beta T cells) is
      cytokine dependent, but the specific requirements differ for each lineage.

PMID- 9602311
TI  - T-cell selection.
AB  - Major histocompatibility complex (MHC) molecules in the thymus select from the
      repertoire of germline receptors those that will be most useful in mounting
      responses to antigen in the periphery. Recent data has shed light on the
      involvement of self peptides presented by the MHC in this process, and has
      indicated that a requirement for the constant recognition of 'self' may be
      essential for T-cell longevity in the periphery.

PMID- 9602312
TI  - B-cell receptor regulation of peripheral B cells.
AB  - Recent studies indicate that immature B cells compete with recirculating B cells
      for survival signals. The signals, delivered through the B-cell receptor for
      antigen, induce immature cells to differentiate into recirculating cells and
      maintain the survival of recirculating cells. They do not induce proliferation or
      differentiation to antibody-producing cells.

PMID- 9602313
TI  - T lymphocyte differentiation in the periphery.
AB  - The development of immune responses is significantly influenced by emerging
      patterns of cytokine expression in activated CD4+ T cells. Recent efforts have
      clarified both cellular and molecular mechanisms, and within the past year
      include significant observations on potential sources of IL-4 leading to Th2
      development against certain pathogens, and insights into early responses and
      genetic susceptibility to experimental murine Leishmaniasis and transcriptional
      regulation of the IL-4 locus. Advances in Th1 development have included greater
      understanding of IL-12 receptors in Th1 development, data regarding IFN-gamma
      gene expression and clarification of the action of the new cytokine IL-18.

PMID- 9602314
TI  - A randomized controlled clinical trial on the efficacy of radiation therapy in
      the control of subfoveal choroidal neovascularization in age-related macular
      degeneration: radiation versus observation.
AB  - BACKGROUND: The results of several pilot studies concerning radiation therapy for
      age-related subfoveal choroidal neovascularization (CNV) have been published
      recently. Although positive treatment results have been described, it is not
      known whether this therapy alters the natural course of eyes with neovascular age
      related macular degeneration (AMD). A randomized controlled clinical trial was
      conducted in which radiation therapy was compared with observation in patients
      with subfoveal neovascular AMD. METHODS: Seventy-four patients with a recent drop
      in central vision due to subfoveal age-related CNV were randomized to either
      radiation treatment or observation. Patients with either classic, occult or mixed
      type CNV were included. Eyes in the treatment group received a radiation dose of
      24 Gy in four fractions of 6 Gy. Evaluation of data concerning visual acuity (VA)
      and fluorescein angiography occurred at 3, 6 and 12 months after inclusion.
      RESULTS: At 12 months of follow-up 52.2% of the observation group versus 32.0% of
      the irradiation group had lost 3 or more lines of VA (P = 0.03, log rank test).
      More severe visual decline, 6 lines or more, was observed in 40.9% of the
      observation versus 8.8% in the irradiation group (P = 0.002 using log rank test).
      At 12 months 39.6% of the observation group and 20.0% of the treatment group had
      VA of less than 0.1 (P = 0.08, log rank test). The size of the CNV membrane
      doubled in 25.2% of eyes in the observation group versus 20.0% in the treatment
      group at least 12 months (P = 0.5, log rank test). No side effects were observed.
      CONCLUSION: Preservation of VA was significantly better in the treatment group
      compared with the control group at 12 months. Nevertheless we noted a drop in
      central vision of 3 or more lines in a substantial proportion of the treatment
      group. Radiation therapy does not prevent visual loss in all patients with age
      related subfoveal CNV, and whether the treatment benefit at 12 months will
      persist has to be awaited.

PMID- 9602315
TI  - Anomaloscope examination in macular gliosis, macular holes and central serous
      choroidopathy.
AB  - BACKGROUND: Surgery for macular gliosis and macular holes has become increasingly
      successful with regard to anatomical outcome. Assessment of the damage to the
      receptors by these processes is still difficult, but is important in predicting
      functional outcome. METHODS: Examination with the Nagel II or the Neitz OT
      anomaloscope was performed in 36 patients with macular gliosis, 23 patients with
      full-thickness macular holes and 47 patients with central serous choroidopathy.
      The anomaloscope matches were expressed as the quotient of anomaly. RESULTS: In
      macular gliosis the mid-matching point is usually 1.0; there is no
      pseudoprotanomaly. In macular holes the mid-matching point is 1.0 when visual
      acuity is 0.3 or greater; in eyes with lower visual acuity there may be signs of
      diminished red sensitivity, but anomaloscope examination becomes difficult. In
      central serous choroidopathy the mid-matching point is shifted towards red, and
      pseudoprotanomaly is present, even when visual acuity is normal. CONCLUSIONS:
      Diseases of the inner retina, in early stages, do not alter colour vision
      substantially, whereas diseases of the outer retina give rise to early colour
      vision deficiency. In macular gliosis and macular holes, anomaloscope examination
      enables estimation of macular receptor misalignment.

PMID- 9602316
TI  - Pleomorphic fibroma of the eyelid.
AB  - BACKGROUND: This report describes the pathology of an unusual variant of fibroma
      of the eyelid. The soft ovoid tumour was excised from the centre of the left
      lower lid in an 84-year-old patient had been growing slowly for several years.
      METHODS: The tumour was studied by conventional histology, immunohistochemistry
      and electron microscopy. RESULTS: The tumor was formed by fibroblasts of spindle
      and multinucleate type, and the collagenous stroma contained mast cells and blood
      vessels which exhibited minor inflammatory changes. With the immunohistochemical
      methods the only positive marker was for vimentin. CONCLUSION: On morphological
      grounds it was possible to distinguish this extremely rare tumour from other
      mesenchymal tumours. The presence of distinctive multinucleate giant cells makes
      the term pleomorphic fibroma an appropriate name for this type of lesion.

PMID- 9602317
TI  - Hemifield association between blue-on-yellow visual field and optic nerve head
      topographic measurements.
AB  - BACKGROUND: Blue-on-yellow (B/Y) perimetry can reveal visual field defects
      earlier and larger in extent than white-on-white (W/W) perimetry. The Heidelberg
      Retina Tomograph (HRT) produces a three-dimensional image of the optic disc. The
      aim of this study was to compare the strength of the association of the B/Y and
      W/W visual hemifield mean deviation (HMD) variables with the optic nerve head
      (ONH) morphological variables of the respective area. METHODS: We evaluated one
      randomly chosen eye of 40 normal subjects and 37 patients with ocular
      hypertension and different stages of glaucoma. The B/Y and W/W visual fields
      (program 30-2) were obtained with a Humphrey perimeter. Results of both visual
      fields were adjusted for the patient's age and lens transmission index measured
      with a lens fluorometer. HMD was calculated as the difference between the
      measured and expected hemifield mean sensitivity values, predicted by the
      regression model fitted in our nonglaucomatous subject data. The HRT with the
      software version 1.11 was used to acquire and evaluate the topographic
      measurements of the optic disc. RESULTS: The B/Y and W/W visual field HMDs showed
      statistically significant correlation with ONH parameters such as cup shape
      measure (CSM), rim volume, rim area, mean retinal nerve fiber layer (RNFL)
      thickness and RNFL cross-sectional area. With forward stepwise logistic
      regression analysis using B/Y hemifield data 38% of the glaucoma patient's normal
      W/W hemifields were classified abnormal. With the CSM alone in the model 52% of
      the cases were classified abnormal. CONCLUSIONS: B/Y visual field hemifield mean
      deviation values correlate well with ONH parameters examined with the HRT.

PMID- 9602318
TI  - Comparison of fluorescein and indocyanine green angiography in angioid streaks.
AB  - BACKGROUND: The main cause of vision loss in patients with angioid streaks is
      choroidal neovascularization and subsequent macular degeneration. Indocyanine
      green angiography allows visualization of the choroidal circulation and may be
      superior to fluorescein angiography in the evaluation of patients with angioid
      streaks. METHODS: The ophthalmoscopic, fluorescein and indocyanine green
      angiographic characteristics of angioid streaks were studied in 34 patients with
      such streaks. Nineteen patients had pseudoxanthoma elasticum and 15 patients had
      isolated angioid streaks. The fluorescence characteristics of the 'peau d'orange'
      and of choroidal neovascularization, when present, were also analyzed. RESULTS:
      Angioid streaks may be hyperfluorescent, hypofluorescent or invisible on
      indocyanine green angiography. Hyperfluorescent streaks were found in 88% of
      eyes, hypofluorescent streaks in 11%; in 18% of eyes some streaks were not
      visualized by indocyanine green angiography. The peau d'orange stained as a
      speckled pattern in the midperiphery; the flecks were concentrated temporal to
      the macula. Eighteen eyes presented classic and 6 occult choroidal
      neovascularization. In several eyes a plaque-like lesion was seen on indocyanine
      angiography that did not correspond to occult choroidal neovascularization on
      fluorescein angiography. CONCLUSION: Indocyanine angiography outlines angioid
      streaks as well as the peau d'orange appearance better than fluorescein
      angiography in the majority of cases. In some cases, however, funduscopically
      visible streaks can not be visualized. Sometimes classic choroidal neovascular
      membranes are not visualized by conventional indocyanine green angiography.
      Occult choroidal neovascularization is better defined by indocyanine green
      angiography. The fluorescence of angioid streaks and of plaque-like lesions makes
      the interpretation of indocyanine green angiography difficult.

PMID- 9602319
TI  - Forecasting of hydrophilic contact lens tolerance by means of tear ferning test.
AB  - BACKGROUND: The ability of the tear ferning test to predict future hydrophilic
      contact lens tolerance was studied. METHODS: The tear ferning test (TFT) was
      performed on one randomly chosen eye of each of the 116 subjects who came to our
      contact lens clinic for hydrophilic contact lens application. The TFT was
      performed at the time of enrollment (TO) and then 1 month (T1), 3 months (T2) and
      6 months (T3) after contact lens fitting. The specificity and the sensitivity of
      the TFT in identifying future contact lens tolerance was then studied. The
      statistical significance of the differences in behavior through the study period
      among the subjects with different pre-fitting TFT results was evaluated by means
      of survival curves. RESULTS: When only type I ferning was considered as a marker
      of good tear film conditions, the ability of the TFT to forecast contact lens
      tolerance had 78.95% sensitivity, 78.35% specificity and 78.45% diagnostic
      precision. The TFT showed sensitivity of 100%, specificity of 86.6% and
      diagnostic precision of 97.4% when performed after 1 month of contact lens
      wearing (T1). Survival curve analysis showed a statistically significant
      difference in behavior between the group of subjects with pre-fitting ferning
      type I and the other three groups (P < 0.001). CONCLUSION: The TFT appears to
      have good sensitivity and specific for prediction of contact lens tolerance in a
      clinical setting.

PMID- 9602320
TI  - Prophylactic argon laser coagulation for rhegmatogenous retinal detachment in
      AIDS patients with cytomegalovirus retinitis.
AB  - BACKGROUND: The incidence of cytomegalovirus (CMV) retinitis in patients with
      acquired immunodeficiency syndrome (AIDS) reaches 20-45%. Despite aggressive
      medical treatment, rhegmatogenous retinal detachments develop in up to 30% of the
      affected eyes. Surgical repair is often difficult due to multiple large and
      hardly visible retinal holes with vitreal traction. Pars plana vitrectomy with
      instillation of silicone oil is the procedure of choice, giving limited
      functional results with anatomical reattachment. METHODS: We performed
      prophylactic laser coagulation in AIDS patients with medically treated CMV
      retinitis to prevent a progressive retinal detachment. Twenty-two quiescent CMV
      lesions in 22 eyes of 20 patients were treated with argon green laser
      coagulation. Each CMV lesion was completely surrounded with a double or triple
      row of laser spots (500-600 mumols; 0.2 s; gray-white lesions). RESULTS: The
      duration of follow-up was 2-24 months. Histopathologic evaluation was possible in
      two eyes of one patient. Reactivated or smoldering CMV retinitis crossed the
      laser scars in 11 eyes, making additional laser coagulation necessary. In four
      eyes retinal holes in the CMV scar tissue led to retinal detachment, which
      stopped at the laser scar. In three eyes the detachment is still controlled by
      the laser scar. In one eye, the detachment stopped at the laser scar for 6.5
      months and then slowly progressed across it. There were no complications
      associated with our laser treatment. CONCLUSION: Prophylactic argon laser
      coagulation in quiescent CMV retinitis seems to reduce the rate of progressive
      retinal detachment with no need for vitrectomy and silicone oil tamponade.

PMID- 9602322
TI  - Equator ring efficacy in maintaining capsular bag integrity and transparency
      after cataract removal in monkey eyes.
AB  - BACKGROUND: The purpose of the study was to evaluate the efficacy of the equator
      ring in maintaining capsular bag integrity at the equator and transparency of the
      posterior capsule after cataract surgery. using cynomolgus monkeys. METHODS:
      After lens removal using an infusion-aspiration method, a flexible silicone ring
      with a groove on its inner surface was inserted in the bag through a window made
      by continuous circular capsulorhexis in six eyes. Of these, four monkey eyes
      underwent posterior chamber intraocular lens (IOL) implantation and two monkey
      eyes did not receive IOLs. Lensectomy without ring insertion was performed as a
      control in the six fellow eyes. Of these, four eyes received an IOL and two did
      not. The eyes were followed for an average of 5.9 +/- 1.1 months before
      enucleation. The effects were evaluated by stereo and light microscopy. RESULTS:
      The ring effectively maintained the circular contour of the capsular bag (ratio
      of the short and long axes, 0.97 +/- 0.01) and posterior capsule transparency (P
      = 0.017). CONCLUSIONS: This study demonstrated that the equator ring is a
      promising device for maintaining capsular bag integrity and minimizing posterior
      capsule opacification after cataract surgery.

PMID- 9602321
TI  - Photodynamic therapy of subfoveal choroidal neovascularization: clinical and
      angiographic examples.
AB  - BACKGROUND: Conventional photocoagulation of subfoveal choroidal
      neovascularization (CNV) is often accompanied by visual loss due to thermal
      damage to adjacent retinal structures. Photodynamic therapy (PDT) allows vascular
      occlusion by selective photochemical destruction of vascular endothelial cells
      only. In a pilot study we evaluated the use of PDT in CNV. METHODS: In a clinical
      phase I/II trial, patients with subfoveal CNV were treated with PDT.
      Benzoporphyrin derivative monoacid ring A (BPD) was used as sensitizer at a drug
      dose of 6 mg/m2 or 12 mg/m2. Irradiation was performed via a diode laser emitting
      at 690 nm coupled into a slit lamp. Safe and maximum tolerated light doses were
      defined by dose escalation from 25 to 150 J/cm2. Photodynamic effects were
      documented ophthalmoscopically and angiographically. RESULTS: Sixty-one patients
      received a single course of BPD-PDT. Preliminary results suggest no damage to
      retinal structures within the treated area clinically. Retinal perfusion was not
      altered, while CNV demonstrated immediate absence of fluorescein leakage in the
      majority of lesions subsequent to PDT. At optimized parameters (6 mg/m2 and 50
      J/cm2) complete cessation of leakage from classic CNV occurred in 100% of cases
      at 1 week and in 50% at week 4. In 70-80% of classic CNV, leakage reappeared at
      week 12, but markedly less than before treatment. CONCLUSION: PDT allows
      temporary absence of leakage from CNV with preservation of visual acuity. The
      long-term prognosis of CNV secondary to age-related macular degeneration treated
      with repeated courses of PDT is being evaluated in a phase III trial.

PMID- 9602323
TI  - Effects of the pharmaceutical cosolvent hydroxypropyl-beta-cyclodextrin on
      porcine corneal endothelium.
AB  - BACKGROUND: The influence of the pharmaceutical cosolvent hydroxypropyl-beta
      cyclodextrin (HPBCD) on porcine corneal endothelium was investigated. The purpose
      was to find out if this substance causes severe damage to the cornea. METHODS;
      One hundred and ninety-five pig corneas were preserved in Eagle's minimal
      essential medium with dextran and HPBCD. They were stained with trypan blue,
      examined using a light microscope and then reincubated. Changes in cell density
      and cell morphology as a function of the duration of preservation and the HPBCD
      concentration were evaluated. We developed a morphological classification
      combining the morphological aspects observed using the light microscope and the
      scanning electron microscope. The vitality of the endothelium was analyzed by
      cell separation and monolayer cultivation. RESULTS: The cell density stayed
      stable without significant alterations in 0.1% HPBCD, 1% HPBDC and control
      solutions. In 10% HPBDC, however, the endothelium showed significant loss of
      cells. The morphological classification revealed high-grade endothelial damage in
      10% HPBDC and low-grade damage in 1% HPBCD. The changes observed in 0.1% HPBCD
      and control medium were comparable. The degree of alteration conformed to the
      results of monolayer cultivation: endothelial cells of damaged corneoscleral
      buttons were limited in their ability to proliferate. CONCLUSION: Severe
      endothelial destruction in 10% HPBCD and changes in membrane integrity at lower
      concentrations limit the use of HPBCD in ophthalmic solutions.

PMID- 9602324
TI  - In vivo fluorescence microscopy of corneal neovascularization.
AB  - PURPOSE: The purpose of our study establish an animal model to study the
      microcirculation in corneal neovascularization in the living animal
      atraumatically. METHODS: Corneal neovascularization was induced in New Zealand
      white rabbits by a standard micropocket assay utilizing pellets with 250 ng basic
      fibroblast growth factor. Anesthesia consisted of intramuscular injections of
      ketamine and xylazine. Intravital microscopy was performed without preparation of
      the cornea. Rhodamine 6G was used as fluorescent dye to stain leukocytes.
      Fluorescein-isothiocyanate-dextran served as plasma marker. Microcirculation
      analysis was done off-line by digital video imaging with special analysis
      software and included the following parameters: vessel diameters, blood velocity,
      and differentiation of leukocytes according to their interaction with endothelium
      into free-floating. rolling and sticking leukocytes. RESULTS: Vessel diameters in
      venular trunk vessels showed diameters of 54.0 +/- 13.3 microns with 1.1 +/- 0.5
      mm/s flow; 29.4 +/- 16.3% of all leukocytes were attached to the vascular wall.
      The number of sticking leukocytes was found to be 17.8 +/- 36.0 cells/mm
      endothelial surface. Values are given for arteriolar trunk and branch as well as
      venular branch vessels. CONCLUSIONS: This method for in vivo microscopic
      observation and quantification of the vasculature of the ocular surface seems to
      be suitable for evaluation of microhemodynamic and leukocyte measurements in
      mature neovascular vessels. It allows atraumatic experiments without corneal
      preparation procedures which disturb the microcirculation. The results concerning
      microhemodynamics and adherence of leukocytes are in a range comparable to other
      microcirculation studies. This new model could provide insight into the
      pathophysiology of microcirculatory disorders of the anterior eye segment, e.g.
      during angiogenesis.

PMID- 9602325
TI  - Renal tumours of childhood.

PMID- 9602326
TI  - Autopsy findings in 27 children with haemophagocytic lymphohistiocytosis.
AB  - AIMS: Primary haemophagocytic lymphohistiocytosis (HLH) is a fatal childhood
      disorder. The diagnosis is difficult to establish, clinically as well as
      histopathologically, and it is markedly underdiagnosed. Because of these
      difficulties, we wanted to elucidate the histopathological findings in population
      based patient material. METHODS AND RESULTS: The post-mortem findings in 27
      children with primary HLH diagnosed in Sweden between 1971 and 1986 was reviewed.
      Twelve of these patients had an affected sibling and three additional children
      had parental consanguinity. Some of the children showed generalized disease,
      whereas in others only one or a few organs were affected. The major histological
      alteration was an accumulation of primarily lymphocytes, but also of histiocytes,
      some of which exhibited evidence of haemophagocytosis. The haemophagocytic
      activity may be difficult to detect if there are pronounced post-mortem changes,
      particularly in the spleen, and it is therefore preferable to perform the autopsy
      as soon as possible after death in order to minimize autolysis. Haemophagocytosis
      was most commonly observed in the spleen (17/24), the lymph nodes (17/23) and the
      bone marrow (9/23), indicating that a negative bone marrow examination does not
      rule out this diagnosis. Three additional patients had discrete signs of
      haemophagocytosis in the bone marrow. In the spleen, the lymph nodes and the bone
      marrow, lymphocytic depletion, pronounced in some cases, could be observed, even
      without prior treatment with steroids or cytostatics. In the liver, most of the
      patients demonstrated an infiltration of lymphocytes into the portal tracts
      similar to that seen in chronic persistent hepatitis (22/27), a finding which is
      uncommon in infancy and therefore suggestive of the diagnosis HLH. Other organs
      involved included the thymus, lungs intestine, pancreas, kidney, heart and
      striated muscle. CONCLUSIONS: The diagnosis of HLH must be based on clinical,
      histological and additional laboratory findings. A negative bone marrow
      examination is common. Previous treatment with steroids and/or cytostatic drugs
      may attenuate or even eliminate the typical histological findings. Liver findings
      similar to those in chronic persistent hepatitis are common.

PMID- 9602327
TI  - CD44 variant expression in inflammatory colonic mucosa is not disease specific
      but associated with increased crypt cell proliferation.
AB  - AIMS: A recent study reported increased epithelial expression of CD44 variants in
      ulcerative colitis (UC) compared with Crohn's disease (CD). However, the use of
      CD44 expression for diagnostic purposes in inflammatory bowel disease has been
      controversial, and the meaning of the appearance of CD44 variants in epithelial
      colonic cells remains unknown. We investigated the relationship between CD44
      isoform expression and crypt cell proliferation in paediatric colitis. METHODS
      AND RESULTS: The expression of CD44v3, CD44v6, and MIB1 (proliferation marker)
      was studied by immunohistochemistry on surgical colonic samples of UC (n = 13),
      CD (n = 10), colostomy resections with non-specific mucosal inflammation (NSMI)
      (n = 3), and normal controls (N = 5). The proliferation index (% of MIB1 positive
      cells) was assessed in both v6 positive and v6 negative crypts. Epithelial
      expression of CD44v3 and v6, negative in normal controls, was variable and focal
      in colitis. No preferential expression of CD44 variants was found in UC. The
      proliferation index was dramatically increased in v6 positive crypts compared
      with v6 negative crypts in UC, CD and NSMI. CONCLUSIONS: These data suggest that
      CD44 variant staining is not a useful marker for distinguishing paediatric UC
      from CD, and that CD44v6 expression in the inflamed colonic mucosa is not disease
      specific but is related to crypt cell proliferation.

PMID- 9602328
TI  - Loss of CD44 variant 6 expression differentiates small cell carcinoma of urinary
      bladder from urothelial (transitional cell) carcinoma.
AB  - AIMS: Small cell carcinoma of the urinary bladder has a more aggressive
      biological potential than urothelial carcinoma, but its morphology may overlap
      with poorly differentiated urothelial carcinoma. The CD44 family of glycoproteins
      mediates cell-cell and cell-matrix adhesion. Aberrant regulation of expression of
      CD44, and particularly its v6 variant exon, has been correlated with aggressive
      or metastatic phenotype of some cancers. We measured the degree of protein
      expression of CD44v6 in small cell and urothelial bladder carcinoma. METHOD AND
      RESULTS: Immunohistochemical staining was performed with monoclonal antibodies
      against CD44v6. Immunoreactivity was absent in 25 of 27 cases of small cell
      carcinoma, with two showing only weak staining of fewer than 10% of cells. In
      contrast, all 12 cases of moderately or poorly differentiated urothelial
      carcinoma displayed moderately intense reactivity in 50% to 100% of cells.
      CONCLUSIONS: CD44v6 immunostaining discriminates cases of poorly differentiated
      urothelial carcinoma from small cell carcinoma. It also highlights the presence
      of mixed small cell urothelial differentiation when present.

PMID- 9602329
TI  - Detection of P-glycoprotein in frozen and paraffin-embedded gastric
      adenocarcinoma tissues using a panel of monoclonal antibodies.
AB  - AIMS: Most chemotherapeutic regimens used against gastric carcinoma include
      anthracyclines whose effectiveness can be impaired by the presence of P
      glycoprotein. In order to obtain a reliable pattern of P-glycoprotein expression
      in these tumours an immunohistochemical study using a panel of anti-P
      glycoprotein antibodies was performed in frozen and paraffinized tissues. METHODS
      AND RESULTS: Frozen and paraffinized samples from 25 gastric carcinomas were
      immunohistochemically analysed using a panel of four anti-P-glycoprotein
      monoclonal antibodies including C219, MRK16, JSB-1 and C494. Semiquantitative
      analysis indicated that moderate or high P-glycoprotein levels were detected in
      40% to 76% of gastric adenocarcinomas, depending on the anti-P-glycoprotein
      antibody used. The antibody C494 was the most sensitive in detecting P
      glycoprotein in both frozen and paraffinized gastric carcinoma samples. Moreover,
      C494 showed a pattern of staining exclusively associated with the plasma
      membrane, in contrast to the cytoplasmic with reinforcement of plasma membrane
      pattern displayed by the other three antibodies. Significant differences in P
      glycoprotein levels were obtained when C494 and MRK16 were used in frozen
      tissues. Finally, detection of P-glycoprotein in frozen samples did not improve
      when compared to paraffinized ones. CONCLUSIONS: It appears that P-glycoprotein
      is frequently expressed in gastric adenocarcinomas, and the use of C494
      complemented by JSB-1 is recommended for reliable detection of P-glycoprotein in
      this neoplasm.

PMID- 9602330
TI  - No evidence for c-erbB-2 overexpression in gastric carcinogenesis.
AB  - AIMS: Conflicting data on c-erbB-2 overexpression in gastric carcinomas can be
      found in the literature with regard to overall prevalence, prognostic
      significance and the histological type according to Lauren. The majority of these
      studies have focused on advanced gastric carcinomas whereas data on c-erbB-2
      overexpression in early gastric carcinomas, especially of Caucasian origin, are
      relatively sparse. We therefore examined a series of Caucasian early gastric
      carcinomas to assess overall c-erbB-2 overexpression and to correlate c-erbB-2
      overexpression, if any, with the type of growth pattern and the Lauren type.
      METHODS AND RESULTS: Forty-five paraffin-embedded gastrectomy specimens from
      early carcinomas were examined for the presence of chronic active gastritis,
      chronic atrophic gastritis, subtypes of intestinal metaplasia and dysplasia. The
      Lauren type and the type of growth pattern were reassessed for all early
      carcinomas. c-erbB-2 overexpression was assessed with monoclonal antibody 3B5 and
      polyclonal antibody A485. Complete absence of c-erbB-2 overexpression was
      observed in chronic active gastritis, chronic atrophic gastritis, subtypes of
      intestinal metaplasia, and dysplasia. Moreover, c-erbB-2 overexpression was found
      absent in both intestinal-type (n = 20) and diffuse-type early gastric carcinomas
      (n = 25), irrespective of growth type. CONCLUSIONS: c-erbB-2 overexpression does
      not play a role in the progression from normal to neoplastic gastric mucosa and
      should be considered as a late event in gastric carcinogenesis. Moreover, c-erbB
      2 overexpression does not discriminate between intestinal and diffuse type early
      gastric carcinomas of Caucasian origin. Finally, it appears that mechanisms other
      than c-erbB-2 overexpression underlie the reported differences in biological
      behaviour of early gastric carcinomas with different types of growth pattern.

PMID- 9602331
TI  - Metallothionein and apoptosis in primary human hepatocellular carcinoma and
      metastatic adenocarcinoma.
AB  - AIMS: Differences in expression of metallothionein (MT) have been reported in
      various human tumours. MT is mainly expressed in proliferating epithelial tumour
      cells but in human hepatocellular carcinoma (HCC) there is only a minimal
      expression of MT. Since MT is a zinc binding protein and certain inducers of MT
      including zinc play a role in apoptosis, studies were undertaken to compare the
      expression of MT and the presence of apoptotic cells (APPC) in both primary HCC
      and metastatic adenocarcinoma. METHODS AND RESULTS: Histological sections of 13
      cases of primary HCC and eight cases of metastatic adenocarcinoma were obtained
      from archival samples. They were stained for MT using a polyclonal antibody which
      crossreacts readily with human MT and for APPC by the TUNEL technique. Normal
      human liver had consistent MT staining with no detectable APPC. The primary HCC
      showed moderate MT staining with a small number of APPC while metastatic
      adenocarcinoma showed no MT staining with a large number of APPC. CONCLUSIONS:
      These results suggest a relationship between absence of MT and appearance of APPC
      in human liver tumours, especially in metastatic adenocarcinomas.

PMID- 9602332
TI  - Localized amyloidosis and gastrointestinal lymphoma: a rare association.
AB  - AIMS: Five cases of primary gastrointestinal (GI) lymphoma (three in the stomach,
      one in the ileum (IPSID) and one in the colon) associated with localized AL
      amyloidosis were studied to identify morphological or immunohistochemical
      features which could explain the amyloid deposition. METHODS AND RESULTS: All the
      cases were low-grade marginal zone B-cell lymphomas; one case of gastric lymphoma
      and the IPSID also had a high-grade component. The lymphomas had a monoclonal
      plasma cell population, with different light and heavy-chain type expression in
      the five cases. Plasma cell differentiation was closely associated with the
      amyloid deposits. The latter were an incidental microscopic finding in one case,
      but produced tumoral masses in the other. CONCLUSIONS: The presence of amyloid in
      primary GI lymphoma is rare, but can have diagnostic value. In the present study,
      neither particular features of the lymphomatous proliferation nor specific agents
      are identified. Therefore, the factors predisposing to amyloid deposition require
      elucidation.

PMID- 9602333
TI  - Solitary plasmacytoma of the lung with light chain extracellular deposits: a case
      report and review of the literature.
AB  - AIMS: We present the clinical and histopathological findings of an unusual
      pulmonary plasmacytoma associated with light chain deposits. METHODS AND RESULTS:
      The tumour was located in the main left stem bronchus 40 mm from the carina.
      Histologically, it was composed of sheets of well differentiated plasma cells.
      Large extracellular deposits of amorphous material were observed in the tumour.
      These deposits were Congo red negative and contained kappa light chains. They
      were electron dense granular and non-filamentous. No plasmacytosis was identified
      by bone marrow biopsy and no monoclonal spike was shown by serum and urine
      electrophoresis. CONCLUSIONS: Our case is unusual in being endobronchial and
      showing light chain deposition.

PMID- 9602334
TI  - Malignant melanoma re-excision specimens--how many blocks?
AB  - AIMS: Wide local excision is commonly undertaken as part of the further
      management of cutaneous melanoma. Although the original excision is usually
      complete, pathologists vary considerably in their macroscopic handling and
      sampling of the wide excision specimens. This study evaluates the sampling of
      reexcision specimens and the information gained from histological examination of
      tissue blocks in order to develop guidelines for the handling of these specimens.
      METHODS AND RESULTS: The study group comprises 219 cases of melanoma which
      underwent initial biopsy followed by wider excision. The macroscopic appearance,
      number of blocks taken and presence of residual melanoma in the wide excision
      specimen was assessed. Residual melanoma was detected in the wide excision
      specimen in only four cases out of the 167 in which the original melanoma had
      been described as completely excised and in these cases the detection of a
      residual lesion reflected either advanced local disease at the time of the
      original excision, or an incompletely excised extensive radial growth phase. The
      sampling of wide excision specimens varied (range of blocks 1-12, average 3.1)
      but statistical analysis showed no undersampling of the wide excision specimens
      in which no residual lesion was found. CONCLUSIONS: These results show that
      detection of a residual lesion in wide excision specimens of melanomas previously
      completely excised is unusual and offers no additional clinically useful
      information. Random block taking in the absence of a macroscopic abnormality is
      therefore unlikely to be clinically useful. Guidelines for the gross handling of
      these wide excision specimens are proposed which are likely to save resources in
      most histopathology departments by reducing block numbers.

PMID- 9602335
TI  - Scalloped cell xanthogranuloma.
AB  - AIMS: We describe nine cases of scalloped cell xanthogranuloma, a distinct
      solitary variant of non-Langerhans cell histiocytoses. METHODS AND RESULTS: In
      this retrospective clinicopathological study scalloped cell xanthogranuloma
      mostly occurred on the back or head and neck of young adult males diagnosed as a
      xanthogranuloma, naevus, or basal cell carcinoma. Histology characteristically
      revealed a sheet-like infiltrate of predominantly scalloped histiocytes (> 79% of
      all cell types) in the upper dermis. Other mononuclear (vacuolated,
      xanthomatized, spindle-shaped, oncocytic) and multinucleate (foreign body, ground
      glass and Touton) histiocytes were also regularly seen. Immunohistochemically,
      all cases exhibited a macrophage/dendritic cell lineage positive with KP1 (CD68),
      KiM1p, HAM 56 and factor XIIIa. Ultrastructurally, numerous intracytoplasmic
      dense, occasionally also myeloid bodies were present. No associated systemic
      disease, hyperlipidaemia or recurrence were seen during follow-up. CONCLUSIONS:
      These findings are similar to those of early lesions of xanthoma disseminatum:
      thus, scalloped cell xanthogranuloma could be regarded as a solitary counterpart
      of xanthoma disseminatum, and, moreover, fits neatly into a unifying concept of
      non-Langerhans cell histiocytoses.

PMID- 9602336
TI  - Fatal pleomorphic xanthoastrocytoma with meningeal gliomatosis.
AB  - AIMS: To report the previously undescribed phenomenon of extensive meningeal
      gliomatosis in a pleomorphic xanthoastrocytoma (PXA) and to examine possible
      prognostic features. CASE DETAILS: An 11-year-old girl underwent excision of a
      left temporoparietal pleomorphic xanthoastrocytoma and 8 months later underwent
      re-excision of a local tumour recurrence. Although mitoses were not present in
      any of the resection specimens, the development of necrosis and increased
      immunoreactivity for proliferating cell nuclear antigen (PCNA) indicated
      anaplastic transformation in the recurrent tumour. Three months later extensive
      meningeal gliomatosis with minimal local recurrence resulted in death.
      CONCLUSIONS: Subarachnoid dissemination of a locally recurrent PXA in the absence
      of mitotic activity is an extremely unusual occurrence. PCNA expression in the
      initial excision specimens did not predict subsequent anaplastic transformation.

PMID- 9602337
TI  - Oncocytic lesions of salivary glands by antimitochondrial immunohistochemistry.

PMID- 9602338
TI  - Tumour angiogenesis and prognosis.

PMID- 9602339
TI  - Is extensive histological examination of wide excision specimens necessary
      following a diagnosis of melanoma.

PMID- 9602340
TI  - Pathogenetic role of the stromal cells in endometriosis and adenomyosis.

PMID- 9602341
TI  - Pathogenetic role of the stromal cells in endometriosis and adenomyosis.

PMID- 9602342
TI  - Demonstration of urate crystals after formalin fixation.

PMID- 9602343
TI  - Amyloid colitis mimicking collagenous colitis.

PMID- 9602344
TI  - Epithelial component of lymphoid stroma-rich Warthin's tumour expresses
      interleukin (IL)-7.

PMID- 9602345
TI  - Transformation of recurrent dermatofibrosarcoma protuberans to its pigmented
      variant (Bednar tumour)

PMID- 9602346
TI  - Carcinosarcoma of the liver.

PMID- 9602347
TI  - Progress in understanding the mechanism and consequences of somatic
      hypermutation.

PMID- 9602348
TI  - Evolution of somatic hypermutation and gene conversion in adaptive immunity.
AB  - Examples of somatic hypermutation of antigen receptor genes can be seen in most
      lineages of vertebrates, including the cartilaginous fish. Analysis of the
      phylogenetic data reveals that two distinctive features of the mechanism are
      shared by most species studied: the mutation hot spot sequence AGY, and a
      preponderance of point mutations. These data suggest that some of the components
      of the machinery are shared between ectotherms and mammals. However, unique
      characters in particular species may have occurred by independent recruitment of
      novel factors onto the mechanism. A spotty phylogenetic distribution of gene
      conversion has also been revealed and can be explained if the two mechanisms
      share some characteristics. Both mutation and conversion require transcription
      related sequences and/or factors. We theorized that targeting to V genes can be
      attained by a paused replication fork that has collided with a transcription
      complex stalled by a defective Ig transcription activator; the paused replication
      fork results in recruitment of an error-prone translesion synthesis DNA
      polymerase (somatic hypermutation) or of DNA repair mechanisms with homologous
      recombination (gene conversion). In addition, the pathway recruited in different
      species may be directed by the degree of homology among V genes.

PMID- 9602349
TI  - Mutation, selection, and memory in B lymphocytes of exothermic vertebrates.
AB  - Unlike mammals, cold-blooded vertebrates produce antibodies of low heterogeneity
      that show little increase in binding affinity with time after immunization. In
      secondary responses, antibody titers and affinities are often little, if any,
      higher than in primary responses. That is, specificity, diversity, and memory-
      the hallmarks of the immune system--are rather meager in the humoral immune
      responses of exothermic vertebrates. As the genetic components of the
      immunoglobulin (Ig) gene systems in fishes, amphibians or reptiles are not
      deficient in number or diversity, their responses probably do not stem from
      restrictions in the primary antibody repertoire. Somatic hypermutation at the Ig
      locus, which generates diversity and higher affinity antibodies in mammals, is
      not lacking in the South African frog Xenopus or in the shark. However, the Ig
      mutants recovered are strongly biased toward alterations at GC pairs, an
      indication that they have not undergone effective selection. While cells
      resembling follicular dendritic cells are present in cold-blooded vertebrates,
      germinal centers do not form. It is suggested that this absence of germinal
      centers, the site of selection for the mutants with higher affinity receptors and
      of differentiation into memory B cells in mammals, may explain the principal
      differences between cold and warm-blooded vertebrates.

PMID- 9602350
TI  - Somatic diversification of IgH genes in rabbit.
AB  - Rabbits have helped elucidate one of the major immunologic puzzles, namely the
      genetic control of antibody diversity. The primary IgH antibody repertoire in
      rabbits is dominated by B cells that use the same germline VH-gene segment in VDJ
      gene rearrangements. The VDJ genes of essentially all B lymphocytes undergo
      somatic diversification within the first few weeks of the rabbit's life. Such
      diversification occurs both by a somatic gene conversion-like mechanism as well
      as by somatic hyperpointmutation. The diversification that occurs early in
      ontogeny takes place in gut-associated lymphoid tissues and potentially depends
      on external factors such as microbial antigens. Few, if any, new B lymphocytes
      develop in adult rabbits and we discuss how the antibody repertoire is maintained
      throughout life. Finally, we discuss the molecular mechanism of somatic gene
      conversion of Ig genes, including the possibility that this involves the use of
      RAD51, an enzyme required for gene conversion-mediated mating type switch in
      yeast.

PMID- 9602351
TI  - Diversification of rabbit VH genes by gene-conversion-like and hypermutation
      mechanisms.
AB  - Where, when and how does VH diversification occur in the rabbit? Early
      diversification by gene-conversion and somatic hypermutation in rabbit appendix
      and chicken bursa of Fabricius are similar processes; the chicken bursa and the
      rabbit appendix have homologous functions. However, diversification in bursa
      starts during embryonic development whereas it starts in rabbit appendix about 2
      weeks after birth in the presence of antigens and superantigens that may
      contribute to positive and negative selection, affect B-cell expansion and mold
      the repertoire. The biochemical steps leading to diversification by gene
      conversion are unknown. However elevated levels of RAD51 mRNA in both chicken
      bursa and young rabbit appendix suggest that repair of double strand breaks may
      be involved. The base changes found in expressed rabbit VH sequences derived from
      rearrangement of known germline VH genes followed by one or more gene conversions
      occur with frequencies similar to those found in analyses of somatic
      hypermutation. The Ser codons in CDR1 and CDR2 of rabbit VH1 genes are all AGY
      rather than TCN, suggesting that they may represent intrinsic hotspots for
      hypermutation comparable to those described in human and mouse VH. Somatic
      hypermutation may further refine antibody affinities in rabbit germinal centers.

PMID- 9602352
TI  - A single VH family and long CDR3s are the targets for hypermutation in bovine
      immunoglobulin heavy chains.
AB  - Bovine immunoglobulins are made from genes belonging to a small family of closely
      related VH genes. In this respect cattle resemble all species of domesticated
      mammals, which also use one VH family. The family, named BoVH1, is homologous to
      the mouse Q52 family, and there are no more than 20 genes of this family in the
      bovine genome. Another feature of bovine heavy chains is the use of long CDR3s,
      which have an average of 21 codons. It seems that there are several families of
      long, closely related D genes rich in glycine and tyrosine responsible for this
      length. Sequences described as targets for mutations in other species can be
      found in CDR1, CDR2, and the putative D genes. The mutation mechanism starts at
      some point between late fetal stage and birth and seems to be antigen
      independent. Diversity seems to be generated by hypermutation, although other
      mechanisms cannot be discounted at this time. Contrary to humans and mice, which
      have several VH gene families comprising more than 100 genes, cattle use only a
      few genes and long CDR3s followed by somatic mutation to generate the necessary
      diversity to recognize the universe of antigens they will encounter during their
      life.

PMID- 9602353
TI  - Recombination-based mechanisms for somatic hypermutation.
AB  - We review some experiments designed to test recombination-based mechanisms for
      somatic hypermutation in mice, particularly mechanisms involving templated
      mutation or gene conversion. As recombination and repair functions are highly
      conserved among prokaryotes and eukaryotes, pathways of mutation in
      microorganisms may prove relevant to the mechanism of somatic hypermutation.
      Escherichia coli initiates a recombination-based pathway of mutation in response
      to environmental stimuli, and this "adaptive" pathway of mutation has striking
      similarities with somatic hypermutation, as does a process of mutagenic repair
      that occurs at double-strand breaks in Saccharomyces cerevisiae. We present a
      model for recombination-based hypermutation of the immunoglobulin loci which
      could result in either templated or non-templated mutation.

PMID- 9602354
TI  - Immunoglobulin hypermutation in cultured cells.
AB  - Studies of endogenous and engineered Ig genes in mice have begun to reveal some
      of the cis-acting regions that are involved in the somatic hypermutation of
      variable regions in vivo. These studies suggest that the initiation of
      transcription plays a role in this process. However, it will be difficult to
      identify and manipulate the individual genetic elements and the trans-acting
      proteins that regulate and target the mutational events using solely in vivo
      assays. These studies would be greatly facilitated if constructs containing the
      genetic elements that are essential for V-region mutation could be transfected
      into cultured cells and undergo high rates of V-region mutation in vitro, and if
      permissive and non-permissive cell lines could be identified. Such in vitro
      systems would also allow a detailed molecular and biochemical analysis of this
      process. Here, we discuss some of the in vitro systems that have been developed
      and use data from our own studies in cultured cells to illustrate the potential
      benefits of studying V-region hypermutation in model in vitro systems.

PMID- 9602355
TI  - Dual enigma of somatic hypermutation of immunoglobulin variable genes: targeting
      and mechanism.
AB  - The immunoglobulin loci are uniquely unstable regions of the genome which undergo
      as much mutation and selection in a matter of days as a species can undergo in
      generations of evolution. We have studied the mutational pattern and targeting of
      this unusual hypermutation process over the past 16 years. The pattern of somatic
      mutations in rearranged variable (V) genes differs from the pattern of meiotic
      mutations, indicating that a different mechanism generates hypermutation than
      generates spontaneous mutation. Hypermutations begin on the 5' end of rearranged
      V genes downstream of the transcription initiation site and continue through the
      V exon and into the 3'-flanking region before tapering off. Mutations are located
      randomly throughout the DNA sequence and exhibit strand bias. The targeting of
      mutations to the region in and around the rearranged V gene appears to require
      interactions between the promoter and downstream intronic DNA sequences. The same
      mechanism that initiates hypermutation around V genes may also produce double
      strand breaks that catalyze homologous recombination between rearranged V genes
      on two chromosomal alleles. With this data we have built a model of hypermutation
      which predicts that V-region DNA is destabilized at the nuclear matrix during
      transcription and undergoes strand breaks.

PMID- 9602356
TI  - Somatic hypermutation in mouse lambda chains.
AB  - The frequency and distribution of somatic hypermutation in immunoglobulin genes
      and the effect of amino acid substitution on the structure/function of antibodies
      were studied using hybridomas that secrete anti-(4-hydroxy-3-nitrophenyl)acetyl
      (NP) monoclonal antibodies bearing lambda 1 chains. A high frequency of mutation
      was observed in V-J exons and J-C introns of rearranged and active lambda 1
      chains but not in the 5'-non-coding regions of these chains. Since a similar
      distribution was observed in inactive lambda 2 chain genes, 5'-non-coding regions
      containing a promoter were considered to be protected from mutation in view of
      their apparent importance. Using transgenic mice carrying chloramphenicol acetyl
      transferase transgenes driven by the VH promoter and heavy-chain intron enhancer,
      it was also revealed that these cis-acting elements are important in the
      induction of somatic hypermutation and are capable of inducing mutation even in
      non-immunoglobulin genes. Affinity of anti-NP Abs to NP increased with time after
      immunization to approximately 8,000-fold (affinity maturation); however, fine
      specificity, such as heteroclicity, remained unchanged. Memory B cells, which are
      responsible for affinity maturation, were analyzed in terms of the mutation from
      Trp to Leu at position 33, a change known to raise affinity about 10-fold and
      considered to be a memory B-cell marker. These cells were found predominantly in
      the early stage (2-3-week) hybridomas but rarely in late stage (> 12-week) ones,
      suggesting that a dynamic change in the memory B-cell population occurs during
      the immunization process.

PMID- 9602357
TI  - Monitoring and interpreting the intrinsic features of somatic hypermutation.
AB  - We have used both normal and transgenic mice to analyse the recruitment and
      targeting of somatic hypermutation to the immunoglobulin loci. We compare methods
      for analysing hypermutation and discuss how large databases of mutations can be
      assembled by PCR amplification of the rearranged V-gene flanks from the germinal
      centre B cells of normal mice as well as by transgene-specific amplification from
      transgenic B cells. Such studies confirm that hypermutation is preferentially
      targeted to the immunoglobulin V gene with the bcl6 gene, for example, escaping
      this intense mutational targeting in germinal centre B cells. We review our data
      concerning the nature of the hypermutation domain and the targeting of hotspots
      within that domain. We consider how enhancer-mediated recruitment of
      hypermutation to the immunoglobulin loci operates in a clonally maintained
      fashion and illustrate how both the degree of expression and demethylation of the
      transgene broadly correlate with its mutability.

PMID- 9602358
TI  - The signature of somatic hypermutation appears to be written into the germline
      IgV segment repertoire.
AB  - We present here a unifying hypothesis for the molecular mechanism of somatic
      hypermutation and somatic gene conversion in IgV genes involving reverse
      transcription using RNA templates from the V-gene loci to produce cDNA which
      undergoes homologous recombination with chromosomal V(D)J DNA. Experimental
      evidence produced over the last 20 years is essentially consistent with this
      hypothesis. We also review evidence suggesting that somatically generated IgV
      sequences from B lymphocytes have been fed back to germline DNA over evolutionary
      time.

PMID- 9602359
TI  - Immunoglobulin gene hypermutation in germinal centers is independent of the RAG-1
      V(D)J recombinase.
AB  - Antigen-driven somatic hypermutation in immunoglobulin genes coupled with
      stringent selection leads to affinity maturation in the B-lymphocyte populations
      present in germinal centers. To date, no gene(s) has been identified that drives
      the hypermutation process. The site-specific recombination of antigen-receptor
      gene segments in T and B lymphocytes is dependent on the expression of two
      recombination activating genes, RAG-1 and RAG-2. The RAG-1 and RAG-2 proteins are
      essential for the cleavage of DNA at highly conserved recombination signals to
      make double-strand breaks and their expression is sufficient to confer V(D)J
      recombination activity to non-lymphoid cells. Until very recently, expression of
      the V(D)J recombinase in adults was believed to be restricted to sites of primary
      lymphogenesis. However, several laboratories have now demonstrated expression of
      RAG-1 and RAG-2 and active V-to-(D)J recombination in germinal center B cells.
      This observation of active recombinase in germinal centers raises the issue of
      RAG-mediated nuclease activity as a component of V(D)J hypermutation. Here, we
      show that a transgenic kappa-light chain gene in a RAG-1-/- genetic background
      can acquire high frequencies of mutations. Thus, the RAG-1 protein is not
      essential for the machinery of immunoglobulin hypermutation. The genetic
      approaches to identifying the genes necessary for somatic hypermutation will
      require further studies on DNA-repair and immunodeficient models.

PMID- 9602360
TI  - Amino acid insertions and deletions contribute to diversify the human Ig
      repertoire.
AB  - The sequence analysis of Ig variable region genes transcribed within different B
      cell subpopulations from human tonsil led us to identify a rare DNA sequence
      modification event consisting of bp insertions and/or deletions (I/D). Although
      these events were previously reported, they had never been formally associated
      with the somatic hypermutation process. I/D events share with more conventional
      somatic hypermutation events their localization within hypervariable regions and,
      most particularly, within DNA motifs known to be mutational hot spots. Repetitive
      DNA tracts or DNA elements capable of forming DNA loop intermediates seem to be
      the preferred substrate for I/D to occur. These characteristics suggest a model
      for somatic hypermutation reminiscent of the "polymerase slippage" model involved
      in replication and repair mutations in prokaryotes, yeast, and mammals.

PMID- 9602361
TI  - Cis-acting sequences that affect somatic hypermutation of Ig genes.
AB  - We review our studies on the mechanism of somatic hypermutation of immunoglobulin
      genes. Most experiments were carried out using Ig transgenes. We showed in these
      experiments that all required cis-acting elements are present within the 10-16 kb
      of a transgene. Only the Ig variable region and its proximate flanks are mutated,
      not the constant region. Several Ig gene enhancers are permissive for somatic
      mutation. Association of the enhancer with its natural Ig promoter is not
      necessary. However, the mutation process seems specific for Ig genes. No
      mutations were found in housekeeping genes from cells with high levels of somatic
      hypermutation of their Ig genes. The Ig enhancers may provide the Ig gene
      specificity. An exception may be the BCL6 gene, which was mutated in human but
      not in mouse B cells. Transcription of a region is required for its mutability.
      When the transcriptional promoter located upstream of the variable region is
      duplicated upstream of the constant region, this region also becomes mutable.
      This suggests a model in which a mutator factor associates with the RNA
      polymerase at the promoter, travels with the polymerase during elongation, and
      causes mutations during polymerase pausing. The DNA repair systems, nucleotide
      excision repair and DNA mismatch repair, are not required. Our recent data with
      an artificial substrate of somatic mutation suggest that pausing may be due to
      secondary structure of the DNA or nascent RNA, and the specific mutations to
      preferences of the mutator factor.

PMID- 9602362
TI  - Analysis of the targeting of the hypermutational machinery and the impact of
      subsequent selection on the distribution of nucleotide changes in human VHDJH
      rearrangements.
AB  - B cells are unique in that they generate and tolerate a high rate of mutations in
      their antigen receptor genes and employ these mutations as a basis of avidity
      maturation. The precise role of the mutational machinery versus subsequent
      selection in determining the frequency and distribution of mutations has not been
      fully analyzed. To address these issues, the influence of the intrinsic
      mutational machinery and subsequent selection on the frequency and distribution
      of mutations in the expressed human immunoglobulin repertoire was analyzed.
      Analysis of non-productively rearranged VH genes from individual human B cells
      provided an opportunity to examine the immediate impact of somatic hypermutation
      without superimposed selective influences. Comparison with the frequency and
      distribution of mutations in the productively rearranged human VH genes permitted
      an estimate of the influences of subsequent selection.

PMID- 9602363
TI  - Affinity selection and repertoire shift: paradoxes as a consequence of somatic
      mutation?
AB  - Affinity selection of antibodies during immune responses relies on two
      mechanisms, one molecular that involves the targeted introduction of somatic
      mutations into rearranged immunoglobulin genes and one cellular that involves the
      clonal expansion of B cells expressing a surface immunoglobulin with a higher
      affinity for antigen compared to their competitors. In this review we focus on
      the conditions for affinity selection during the establishment, expansion and
      memory phases of the immune response. We postulate that somatic mutation evolved
      prior to affinity selection and we present a model for selection of B cells in
      germinal centres. We also discuss the possibility that antibody repertoire shift
      occurs during the memory maintenance phase. Finally, we argue that a significant
      affinity selection and a selection for polyclonality of immune responses occur
      during this stage of the immune response.

PMID- 9602364
TI  - The roles of antibody variable region hypermutation and selection in the
      development of the memory B-cell compartment.
AB  - Somatic hypermutation and selection of immunoglobulin (Ig) variable (V)-region
      genes, working in concert, appear to be essential for memory B-cell development
      in mammals. There has been substantial progress on the nature of the cis-acting
      DNA elements that regulate hypermutation. The data obtained suggest that the
      mechanisms of Ig gene hypermutation and transcription are intimately intertwined.
      While it has long been appreciated that stringent phenotypic selection forces are
      imposed on the somatically mutated Ig V regions generated during a T-cell
      dependent B-cell response, the mechanisms involved in this selection have
      remained enigmatic. Our studies have questioned the role of foreign antigen
      deposited on follicular dendritic cells in affinity-based positive selection of V
      regions, and have shown that this selection takes place in a "clone-autonomous"
      fashion. In addition, our data strongly suggest that affinity for antigen alone
      is not the driving force for selection of B-cell clones into the memory
      compartment. In contrast, we suggest that a combination of positive selection for
      increased foreign antigen binding, and negative selection of antibody V regions
      that are autoreactive at the onset of the response, or have acquired
      autoreactivity via hypermutation, results in the "specificity maturation" of the
      memory B-cell response.

PMID- 9602365
TI  - Harmful somatic mutations: lessons from the dark side.
AB  - The ability of somatic mutation to modify the course of an immune response is
      well documented. However, emphasis has been placed almost exclusively on the
      ability of somatic mutation to improve the functional characteristics of
      representative antibodies. The harmful effects of somatic mutation, its dark
      side, have been far less well characterized. Yet evidence suggests that the
      number of B cells directed to wastage pathways as a result of harmful somatic
      mutation probably far exceeds the number of cells whose antibodies have been
      improved. Here we review our recent findings in understanding the structural and
      functional consequences of V-region mutation.

PMID- 9602366
TI  - Antibody feedback and somatic mutation in B cells: regulation of mutation by
      immune complexes with IgG antibody.
AB  - In response to an appropriate antigenic stimulus, and with help from T
      lymphocytes, naive B cells differentiate into plasmacytes which produce the
      primary (germline-encoded) IgM and IgG antibody with low affinity for the
      antigen. The isotype switch from IgM to IgG coincides with the burst of germinal
      center reaction and the onset of somatic hypermutation. Here we propose that
      formation of immune complexes between the residual antigen and the primary IgG
      antibody, which activate complement and localize specifically in the network of
      follicular dendritic cells, provides an important signal for triggering the
      mutation mechanism in germinal center B cells. This hypothesis has been supported
      by studies on immunogenicity of immune complexes in vivo. The experiments have
      included an immunization with pre-formed antigen/IgG antibody complex and/or an
      administration of IgG antibody shortly after the antigen injection. Either of
      these strategies, which are known to augment the germinal center formation,
      resulted in earlier onset of somatic mutation and increased mutation frequency in
      VDJ rearrangements in antigen-reactive B cells, provided that help from T cells
      was also present. It is presumed that the antigen/antibody/complement complex is
      able to deliver this important signal by cross-linking of antigen receptor with
      the CD21/CD19/CD81 molecules on B cells. As a corollary, the signaling by immune
      complexes may lower the threshold of cell activation determined by receptor
      affinity for antigen and stimulate diverse V-gene repertoire of B-cell clones in
      germinal centers.

PMID- 9602367
TI  - Somatic hypermutation in autoimmune thyroid disease.
AB  - Autoimmune thyroid disease is one of the most common autoimmune diseases. There
      is typically patient antibody (Ab) reactivity to one or more of the antigens
      thyroglobulin (Tg), thyroid peroxidase (TPO) and the thyroid simulating hormone
      receptor (TSHr). With the advent of combinatorial library technology, there has
      been an enormous increase in the number of sequences from Ab to Tg and TPO. The
      repertoire of both Tg and TPO Ab is restricted and indicates the importance of
      somatic hypermutation in the development of the high affinity Ab response.
      However, there are still too few sequences to determine patterns in which the
      mutation occurs, which residues are introduced during substitution and how
      individual substitutions affect the affinity of the Ab. Ab to the TSHr are of far
      greater pathological significance than those to Tg and TPO, but the current
      repertoire of Ab to the TSHr has yet to include the high affinity IgG Ab
      characteristic of patient serum Ab. Instructive analysis of the role of somatic
      hypermutation in the development of TSHr Ab therefore still awaits the isolation
      of the pathologically active repertoire. Despite this, the Ab response in thyroid
      autoimmunity remains one of the best characterised of human autoimmune diseases.

PMID- 9602368
TI  - Somatic origin of T-cell epitopes within antibody variable regions: significance
      to monoclonal therapy and genesis of systemic autoimmune disease.
AB  - During an immune response, specific antibody variable region genes are
      diversified by a somatic point mutation process that generates de novo "foreign"
      V-region sequences. This creates an interesting problem in immune regulation
      because B cells are highly proficient at self-presenting V-region peptides in the
      context of class II MHC. Though our studies indicate that the corresponding T
      cell repertoire attains a state of tolerance to germline-encoded antibody V
      region diversity, it is presently unknown whether the same is true of
      mutationally generated diversity. On the basis of immunoregulatory
      considerations, we hypothesize that contact exclusion or tolerance normally
      precludes T cells from helping B cells via self-presented mutant V-region
      peptides. The lack of recurrent somatic mutations that create known T-cell
      epitopes in antibody V regions lends some support to this idea. In contrast, our
      studies of spontaneously autoreactive B cells in systemic autoimmune disease
      strongly suggest that precursors of such cells are recruited by T-cell help
      directed to self-presented mutant idiopeptides. Failures in tolerance or contact
      exclusion mechanisms may be responsible for this apparently abnormal event. In
      addition to their importance in immune regulation, somatic mutations or other
      differences from germline-encoded V-region sequence may be largely responsible
      for undesirable patient responses to therapeutic monoclonal antibodies. These
      reactions might be averted or diminished by inducing tolerance in the T-cell
      repertoire with synthetic peptide correlates of non-germline-encoded V-region
      sequences in humanized antibodies.

PMID- 9602369
TI  - Insight into the origin and clonal history of B-cell tumors as revealed by
      analysis of immunoglobulin variable region genes.
AB  - Recombination of VH, DH and JH genes is a unique first step in normal B-cell
      development. Subsequent differentiation to a mature plasma cell is accompanied by
      further events in the Ig genes, including VL-JL joining, somatic hypermutation
      and isotype switching. Chromosomal changes leading to B-cell tumors can occur at
      many points in this sequence, and may be partly a consequence of the genetic
      mobility and mutability permitted in order to generate a diverse antibody
      repertoire. V genes of neoplastic B cells may reflect the point of maturation
      reached by the B cell of origin, prior to transformation. Analysis of tumors
      therefore provides useful information on V-gene patterns in normal B cells, and
      may add another dimension to classification of B-cell tumors. Transformation may
      also preserve cell populations normally destined to die by apoptosis. Tumor cells
      arrested in the site where somatic hypermutation and isotype switch are occurring
      can still be subject to these processes, and could be influenced by persisting
      antigen. However, mutation is silenced at the point of exit to the periphery,
      leading to fixed mutational patterns in tumors of mature B cells. V-gene analysis
      provides an invaluable tool for understanding the genesis of neoplastic change.
      It also has a clear clinical relevance in tracking tumor cells, measuring
      residual disease, and finally in offering the opportunity of developing vaccines
      for treatment.

PMID- 9602370
TI  - Somatic hypermutation in normal and transformed human B cells.
AB  - In the human, most IgM+IgD+ as well as CD5+ peripheral blood B cells express
      unmutated V genes and thus can be assigned to a pre-germinal centre (GC) stage of
      development. The memory B-cell compartment generated in the GC reaction and
      characterized by cells bearing somatically mutated V-region genes consists not
      only of class-switched cells, but also of IgM-only B cells and perhaps a subset
      of IgM+IgD+B cells expressing the CD27 antigen. Comparison of the rearranged V
      region genes of human B-cell lymphomas with those of the normal B-cell subsets
      allows the identification of the progenitor cells of these tumours in terms of
      their stage of maturation. On this basis, most B-cell non-Hodgkin lymphomas, and
      in addition Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin's disease (HD), are
      derived from B cells at a GC or post-GC stage of development. The mutation
      pattern indicates that the precursors of the tumour clones have been stringently
      selected for expression of a functional antigen receptor with one notable
      exception: HRS cells in classical (but not lymphocyte-predominant) HD appear to
      be derived from "crippled" GC B cells. Sequence analysis of rearranged V genes
      amplified from single tonsillar GC B cells revealed that the somatic
      hypermutation process introduces deletions and/or insertions into V-region genes
      more frequently than indicated by previous investigations. Presumably, this
      feature of the hypermutation mechanism is often responsible for the generation of
      heavy chain disease, and also several types of chromosomal translocations of
      oncogenes into immunoglobulin loci in human B-cell lymphomas.

PMID- 9602371
TI  - Somatic hypermutation of immunoglobulin variable region genes: focus on
      follicular lymphoma and multiple myeloma.
AB  - Analysis of the rearranged immunoglobulin variable region gene hypermutation has
      provided important information concerning the clonal history and ontogenetic
      origin of various B-cell lymphoproliferative disorders. Under the selective
      pressure of antigen, mutational events in immunoglobulin genes will fine tune
      survival of B-cell clones bearing immunoglobulin with high affinity for antigen.
      Our studies aimed at analyzing neoplastic disorders originating from germinal and
      post-germinal center B-cells: follicular lymphoma and multiple myeloma,
      respectively. Despite the already acknowledged evidence for a selectable
      distribution of mutations within the clonal immunoglobulin variable heavy chain
      genes, very little is known about the contribution of light chains in the process
      of antigen selection. In follicular lymphoma, a more limited pattern of somatic
      mutation with less evidence of antigen selection was observed in variable kappa
      light chain genes (40%) than in their partner heavy chain genes (80%). In
      myeloma, hypermutation of variable light chain genes, with a distribution
      suggestive of antigen selection, was frequently observed. Based on these data and
      recent reports it appears that the light chain expressed by the clonogenic
      myeloma B-cells plays a pivotal role in the antigen selection process.
      Additionally, abortive kappa light chain variable region genes in lambda
      expressing myelomas carried a significant number of somatic mutations indicating
      that the cell of origin is open to the hypermutation machinery at that particular
      developmental stage irrespective of antigen selection.

PMID- 9602372
TI  - The immunology of AIDS-associated lymphomas.
AB  - Lymphomas that occur in patients with human immunodeficiency virus (HIV)
      infection are predominantly of B-cell origin and subsets show evidence for
      Epstein-Barr virus (EBV) infection or chromosomal translocations in the c-myc
      locus. The only subset of lymphoma clearly related to the immunodeficiency caused
      by HIV infection (similar to transplantation-associated lymphomas) is the EBV+
      primary central nervous system lymphoma. The systemic AIDS-related lymphomas
      (ARLs) represent a complex set of disease processes histologically categorized as
      large cell or small non-cleaved (Burkitt's-like) lymphomas. Molecular analyses of
      the ARLs have demonstrated polyclonal lymphomas as likely early representatives
      of monoclonal immunoglobulin (Ig)-expressing B-cell lymphomas. Variable region
      analysis of lymphoma-associated Ig has shown evidence for extensive somatic
      mutation with little evidence for appropriate affinity maturation. These
      observations suggest that abnormal control of B-cell maturation in response to
      polyclonal antigenic stimulation may play a central role in the pathogenesis of
      ARL. The recent finding of clonal HIV integrated within macrophages in a subset
      of early lymphomas also provides evidence for abnormalities outside the B-cell
      compartment playing roles in this disease. Overall, ARLs generally appear to be
      outgrowths of antigen-driven B-cells with significant growth control influence
      provided by abnormal T-cell and antigen-presenting cell processes.

PMID- 9602373
TI  - HLA class II antigens are associated with resistance or susceptibility to
      hepatosplenic disease in a Chinese population infected with Schistosoma
      japonicum.
AB  - The major histocompatibility Class II alleles of 108 individuals living in an
      area endemic for schistosomiasis japonica in China were determined to identify
      possible immunogenetic associations with advanced schistosomiasis. Two alleles,
      HLA-DRB1*1202 (P = 0.002) and HLA-DQA*0601 (P = 0.001) were strongly associated
      with resistance to advanced disease. In contrast, HLA-DQB1*05031 (P = 0.02) was
      associated with susceptibility to advanced schistosomiasis. The remaining alleles
      showed no association with advanced disease. Allele DRB1*1202 co-occurred with
      allele DQA1*0601; therefore, their independent protective effects could not be
      ascertained. In contrast, alleles DQA1*0601 and DQB1*05031 never co-occurred and
      had opposite and significant effects on the occurrence of disease.

PMID- 9602374
TI  - Nestedness in assemblages of metazoan ecto- and endoparasites of marine fish.
AB  - Assemblages of metazoan ectoparasites of 79 species and gastrointestinal
      helminths of eight species of marine fishes were analysed to examine whether
      nestedness is related to sample size, abundance, species richness, and prevalence
      of infection, and whether the use of z-scores or Monte Carlo simulations yields
      different results. No significant differences in the number of nested assemblages
      were found with the two methods, and neither sample size nor abundance, but
      prevalence of infection of ectoparasites was correlated with nestedness. Species
      richness was significantly correlated with nestedness only when fish species with
      fewer than three parasite species were not excluded. Differential colonisation
      probabilities are the most likely cause of nestedness.

PMID- 9602375
TI  - Complex dynamic behaviours in the interaction between parasite population and the
      host's immune system.
AB  - The paper describes recent progress in the development of a mathematical
      framework for the study of epidemiology, evolution, within-host parasite
      population growth and the control of parasitic infections. A major emphasis is
      placed on dynamic models of the interaction between the parasite population and
      the host's immune system that capture the effects of antigenic variation,
      parasite evolution in response of immunological attack and the control of
      population growth by chemotherapeutic agents.

PMID- 9602376
TI  - Mitochondrial function in Babesia microti and Babesia rodhaini.
AB  - The role of mitochondria in the energy metabolism of Babesia microti and Babesia
      rodhaini was investigated. A variety of mitochondrial inhibitors showed greater
      sensitivity to B. microti than to B. rodhaini. Additionally, alpha
      glycerophosphate- and succinate-cytochrome c reductase activities in the crude
      mitochondrial fraction from B. microti were substantially higher than those from
      B. rodhaini. Our results suggest that the mitochondria of these parasites possess
      a series of "classical" apparati for energy production and their relative
      functional role may be quantitatively greater in B. microti when compared with B.
      rodhaini.

PMID- 9602377
TI  - Population dynamics of the monogenean Anoplodiscus cirrusspiralis on the snapper,
      Pagrus auratus.
AB  - Populations of Anoplodiscus cirrusspiralis were monitored for 1 year on tagged
      individual snapper in experimental cages kept in a large on-shore pond with flow
      through filtered sea water. The cages were stocked with small and large fish at
      either low or high initial density. Irrespective of size and density, snapper
      with light initial infections maintained light infections, whereas fish with
      heavy initial infections showed fluctuations in parasite population size
      throughout the year. These data indicate that some snapper have an innate
      resistance to infection by A. cirrusspiralis, with little evidence for acquired
      immunity induced by heavy infection. Parasite longevity was greater on the
      pectoral fin than caudal fin, and greater on large than small fish irrespective
      of fish density; longevity was greater on susceptible fish than on resistant
      fish. Recruitment and mortality rates were greater on the pectoral fin and in low
      density cages, but were influenced by fork length.

PMID- 9602378
TI  - Immunosuppressive and antiparasitic effects of cyclosporin A on Hymenolepis nana
      infection in mice.
AB  - The effect of cyclosporin A, which is known to act both as immunosuppressant and
      as an antiparasitic drug in many host-parasite systems, was examined in a mouse
      Hymenolepis nana system. When BDF1 mice were injected s.c. with cyclosporin A
      (100 mg kg-1 day-1) every 48 h from 11 days p.i. with eggs, expulsion of the
      adult worms from the intestines of mice was prevented completely until at least
      30 days p.i. Worm burden, dry weight and the number of gravid proglottids were
      not significantly reduced. By contrast, in untreated mice most of the worms were
      eliminated by 19 days p.i. The drug also completely abolished acquired resistance
      to a challenge infection with eggs when mice were injected s.c. with cyclosporin
      A (100 mg kg-1 day-1) around the time of challenge infection (Days -2, -1, 0, 1
      and 2 relative to challenge). Such immunosuppressive effects of cyclosporin A on
      worm expulsion and protective immunity to reinfection were similar to those of
      another immunosuppressant, cyclophosphamide. As for the antiparasitic action of
      cyclosporin A against H. nana, a smaller number of cysticercoids developed from
      eggs in mice given cyclosporin A (100 mg kg-1 day-1) for 5 days beginning 1 day
      before infection, than in untreated controls.

PMID- 9602379
TI  - Presence of IgM antibodies to Trypanosoma cruzi urinary antigen in sera from
      patients with acute Chagas' disease.
AB  - An 80-kilodalton Trypanosoma cruzi antigen is eliminated in the urine of infected
      hosts during the acute stage of Chagas' disease. We show that affinity-purified
      urinary antigen is recognised by IgM antibodies in the sera from acute chagasic
      patients. Comparing our urinary antigen assay with that using a whole T. cruzi
      lysate antigen for IgM antibody detection, we demonstrated that ELISA with
      urinary antigen increases the diagnostic sensitivity and specificity of IgM
      serology in recent chagasic infection. Twenty-six of 30 patients with acute T.
      cruzi infection had serum IgM antibodies that reacted with urinary antigen by
      ELISA, while lysate antigen IgM was detected in 24 sera. When sera from patients
      suffering other parasitoses were tested, strong cross-reactions occurred in ELISA
      with T. cruzi lysate antigen, whereas ELISA with urinary antigen proved to better
      discriminate acute chagasic patients. Human antibodies to urinary antigen
      immunoprecipitated this T. cruzi urinary antigen and also inhibited the binding
      of monoclonal antibody to urinary antigen in an inhibition assay. These findings
      suggest that urinary antigen may be useful for the development of serodiagnostic
      procedures for acute T. cruzi infection.

PMID- 9602380
TI  - Single-species infections of Echinostoma caproni cercariae in pulmonate snails
      and concurrent infections of E. caproni and Echinostoma trivolvis cercariae in
      Biomphalaria glabrata.
AB  - Single-species infections of Echinostoma caproni cercariae in various pulmonate
      snails showed that a higher percentage of cercariae encysted successfully in
      Biomphalaria glabrata than in other snail species and that the percentage
      encystment was significantly greater in B. glabrata than in either Helisoma
      trivolvis or Lymnaea elodes. There were significant differences in cyst diameter,
      thickness of outer and inner cysts, and diameter of excretory concretions between
      E. caproni and Echinostoma trivolvis metacercariae. These morphological
      differences helped to distinguish each species of cyst in concurrent cercarial
      infections of E. caproni and E. trivolvis in B. glabrata. Moreover, in concurrent
      infections E. trivolvis localised only in the saccular kidney, whereas E. caproni
      occurred in both the saccular kidney and the pericardium.

PMID- 9602381
TI  - Influence of trematode parasitism on the growth of a bivalve host in the field.
AB  - Trematode-induced gigantism of molluscs, enhanced growth of trematode-parasitised
      individuals, has been observed in many laboratory studies. This study reports the
      effect of the sterilising trematode, Rhipidicotyle fennica, on the growth of the
      freshwater clam Anodonta piscinalis under field conditions. In addition to single
      infections (prevalence 44%), a few clams (3%) were infected with both R. fennica
      and Rhipidicotyle campanula. Parasite-induced gigantism was not found; parasites
      lowered host growth. The decreased in growth was correlated with the quantity of
      parasite material. Clams with double infections grew the least, although they did
      not differ significantly from hosts with a heavy single species infection. The
      growth of the experimental clams was lower than that of undisturbed control
      clams. Trematode-induced gigantism of molluscs in the field, in general, remains
      undemonstrated.

PMID- 9602382
TI  - Viability of metacercariae of Clonorchis sinensis in frozen or salted freshwater
      fish.
AB  - Metacercariae of Clonorchis sinensis were collected from freshwater fish
      (Pseudorasbora parva) after storage in a freezer at -12 degrees C for 10-20 days,
      in a freezer at -20 degrees for 3-7 days, or treating with heavy salt (fish/salt
      = 10 gm/3 gm) at 26 degrees for 5-15 days. The metacercariae from the frozen fish
      were inoculated into 30 rats and eight rabbits, and those from the salted fish
      into 33 rats. Metacercariae from freshwater fish stored at -12 degrees for 10-18
      days or -20 degrees for 3-7 remained viable and infective. Moreover, those kept
      at the heavy salt concentration for 5-7 days remained viable and infective. These
      findings indicate that freezing or storing infected freshwater fish in heavy salt
      may not be effective in the prevention of clonorchiasis. However, it appears that
      refrigeration, or keeping the fish in salt for longer periods, may be suitable
      for prevention of the infection.

PMID- 9602383
TI  - First report of the isolation of an adult worm of the genus Brachylaima (Digenea:
      Brachylaimidae), from the gastrointestinal tract of a human.
AB  - A 78-year-old woman presented with an 18-month history of intermittent diarrhoea.
      Examination of her stools revealed brachylaimid eggs, which were present in three
      separate specimens over a week. After treatment with praziquantel a degenerate
      adult Brachylaima species was recovered from her faeces. She lived in a rural
      area of South Australia and ate vegetables grown in her own garden which had been
      infested with helicid snails. In south Australia these introduced European
      helicid snails are commonly infected with brachylaimid intermediate larval stages
      and are considered to be the source of the human infection.

PMID- 9602385
TI  - Differences in the 5.8S rDNA sequences among ascarid nematodes.
AB  - Sequences of the 5.8S rDNA were obtained for 14 species of nematode from
      different superfamilies and families within the order Ascaridida. All sequences
      were 157 bp in length. Sequence differences among species ranged from 0 to 18 bp
      (0-11.5%). A phenetic analysis of the sequence data groups the 14 taxa into their
      respective superfamilies and families, but does not discriminate fully at the
      subfamily level. A phylogenetic analysis of the sequence data failed to resolve
      the evolutionary relationships at the superfamily level. The 5.8S gene may be
      useful for phylogenetic studies of the phylum Nematoda at the ordinal level.

PMID- 9602384
TI  - Necator americanus (Nematoda: Ancylostomatidae) from Africa and Malaysia have
      different ITS-2 rDNA sequences.
AB  - The nucleotide sequences of the second internal transcribed spacer of rDNA were
      determined for adult worms of Necator americanus originating from Togo (Africa)
      and Sarawak (Malaysia). The length of the sequences of specimens from Togo (325
      bp) were shorter than those from Sarawak (327 bp). There were six fixed genetic
      differences in the aligned sequences of N. americanus from Sarawak and Togo,
      excluding one or two polymorphic sites within the sequence of N. americanus from
      each geographical region. These findings suggest that there is either population
      variation in the sequence of N. americanus, or that N. americanus from the two
      countries may represent genetically distinct but morphologically similar (i.e.
      cryptic) species, however, comparison of the sequence differences among other
      hookworm species supports the latter conclusion.

PMID- 9602386
TI  - A direct competitive ELISA for the simple, sensitive and accurate determination
      of diethylcarbamazine concentration in serum.
AB  - Improved methods for measurement of the anti-filariasis drug diethylcarbamazine
      in serum would assist in the design of effective therapy. The method evaluated in
      the present paper is a direct competitive ELISA which is sensitive, specific and
      accurate. Horseradish peroxidase-labelled diethylcarbamazine conjugate was
      incubated with diethylcarbamazine and anti-diethylcarbamazine antiserum over a
      bound second antibody. The enzyme activity of the remaining diethylcarbamazine
      horseradish peroxidase conjugate was measured. The intra- and inter-assay
      coefficient of variation was < 10% in the range of 1.0-30 ng ml-1 and the limit
      of detection was 0.3 ng ml-1. The cross reactivities of anti-diethylcarbamazine
      antibodies with diethylcarbamazine metabolites and ivermectin were < 0.09%. Using
      the ELISA, the serum levels of diethylcarbamazine were successfully determined in
      mongolian jirds (Meriones unguiculantus) up to 4h following a single dose of 50
      mg kg-1 of body weight. The values of pharmacokinetic parameters of
      diethylcarbamazine in jirds were determined.

PMID- 9602387
TI  - An in-vitro test for assessing the viability of Ascaris suum eggs exposed to
      various sewage treatment processes.
AB  - A simple procedure using Ascaris suum as a model for Ascaris lumbricoides in
      testing the ability of sludge treatment processes to kill the eggs of parasitic
      roundworms was developed. Unembryonated and embryonated A. suum eggs were placed
      in a mesophilic anaerobic sludge digester or a sludge lagoon, or stored at 4
      degrees C. Unembryonated eggs were recovered and incubated at 32.5 degree C and
      90-95% r.h. for 48 h and viable eggs developed embryos consisting of two or more
      clearly defined cells. This viability was confirmed by further incubation for 30
      days, when motile first-stage larvae were seen. Infectivity was demonstrated by
      administering larvated eggs to worm-fee pigs and recovering adult worms from the
      small intestine at necropsy. After 1 week in a mesophilic anaerobic digester, 95%
      of A. suum eggs produced two-cell larvae into vitro, with 86% progressing to
      motile larvae. After 5 weeks in the digester 51% progressed to motile larvae.
      Between 42% and 49% of eggs stored in a sludge lagoon for 29 weeks were viable
      and able to develop motile larvae. In the case of eggs that were embryonated
      before treatment, > 98% survived up to 5 weeks in the digester and were able to
      develop motile larvae. More than 90% of embryonated eggs survived for 29 weeks in
      the sludge lagoon and were able to develop motile larvae.

PMID- 9602388
TI  - Antimalarial and cytotoxic potential of four quassinoids from Hannoa chlorantha
      and Hannoa klaineana, and their structure-activity relationships.
AB  - Hannoa chlorantha and Hannoa klaineana (Simaroubaceae) are used in traditional
      medicine of Central African countries against fevers and malaria. Four stem bark
      extracts from H. klaineana and four quassinoids from H. chlorantha were examined
      in vitro against Plasmodium falciparum NF 54. The extracts displayed good
      activities, while the quassinoids were highly active, with IC50 values well below
      1 microgram ml-1, those of chaparrinone and 15-desacetylundulatone being much
      lower than 0.1 microgram ml-1 (0.037 and 0.047 microgram ml-1, respectively).
      Chaparrinone is five times more active than 14-hydroxychaparrinone against P.
      falciparum, indicating that the hydroxyl function at C-14 is unfavourable for
      antiplasmodial activity. As 14-hydroxychaparrinone has a seven-times higher
      cytotoxic activity against P-388 cells than chaparrinone, the latter compound has
      the better antiplasmodial therapeutic index. All four quassinoids were evaluated
      in vivo in a standard 4-day test as well. 15-Desacetylundulatone was proven to be
      the most active compound, almost totally suppressing the parasitaemias of OF1
      mice for at least 7 days, while both chaparrinone and 14-hydroxychaparrinone were
      active for at least 4 days. Quassinoids have ED50 values much lower than 50 mg kg
      1 body weight day-1 and none of them caused obvious side effects. The keto
      function at C-2 in 15-desacetylundulatone is apparently of crucial importance for
      its high activity. 6-alpha-Tigloyloxyglaucarubol was not active at all.
      Chaparrinone is considered the most interesting of the investigated quassinoids
      and its in-vivo antimalarial potential will be examined further.

PMID- 9602389
TI  - High-level chloroquine resistance of Plasmodium berghei is associated with
      multiple drug resistance and loss of reversal by calcium antagonists.
AB  - The chloroquine resistance of Plasmodium falciparum is reversed in vitro by
      numerous compounds, including calcium antagonists, which could enhance the
      accumulation of the drug in the parasite food vacuole. However, this mechanism of
      resistance could be insufficient when the resistance level increases. Using in
      vitro drug trials on strains of Plasmodium berghei displaying various chloroquine
      resistance levels, we confirmed previous results obtained in vivo in the
      chloroquine-resistant strains of P. berghei are cross-resistant to related drugs
      (amodiaquine, quinine and mefloquine), the resistance levels to these drugs being
      related to their analogy to chloroquine. Furthermore, we showed that high-level
      resistant lines were associated with a loss of drug potentiation by verapamil and
      nicardipine in vivo, but that the reversal rates obtained in vitro are of low
      significance. We conclude that the parasite is able to escape the activity of
      these reversing agents.

PMID- 9602390
TI  - Glands associated with the anterior adhesive areas of the monogeneans, Entobdella
      sp. and Entobdella australis (Capsalidae) from the skin of Himantura fai and
      Taeniura lymma (Dasyatididae).
AB  - Using scanning and transmission electron microscopy, investigations were carried
      out on the anterior adhesive areas of Entobdella sp. from the skin of Himantura
      fai and Entobdella australis from the skin of Taeniura lymma at Heron Island,
      Australia. All studies were of parasites detached from either host tissue or a
      substrate. Both species of monogeneans have two characteristic anteroventral
      adhesive pads, one on either side of the head, subdivided to a "diadem". Two
      types of gland cells are associated with the anterior adhesive areas in both
      species and each cell type produces a different secretion: a rod-shaped secretion
      and a smaller, roughly spherical secretion. Each secretion type differs in
      electron-density, with those putatively in the process of formation being less
      electron-dense. Both types of secretory bodies are membrane-bound. Microtubules
      are evident around forming rod-shaped bodies. The bounding membranes of the rods
      of both species show a periodic banding of approximately 12 nm. Both types of
      secretion are present at the surface of the adhesive pads in specimens of
      Entobdella sp. fixed when detached from the host. The secretory bodies observed
      in Entobdella sp. and E. australis from rays show some differences to those
      reported from Entobdella soleae, a parasite of a flatfish teleost. Other
      ultrastructural differences also exist. We conclude that the types of adhesive
      secretory bodies may remain constant within genera providing the hosts are
      similar.

PMID- 9602391
TI  - Ultrastructure of presumed sensory receptors in the scolex of adult
      Proteocephalus exiguus (Cestoda, Proteocephalidea).
AB  - The ultrastructure of six type of putative sense receptors including three
      nonciliate (Types I-III) and three ciliate (Types IV-VI) types found in the
      tegument of the scolex of adult Proteocephalus exiguus has been described for the
      first time. Type I has a simple tegumental sensory ending, containing one
      electron-dense collar, circular septate desmosome, electron-lucent vesicles and
      microtubules. Type II is represented by a receptor with a large rootlet. Type III
      is a receptor with a very long cross-striated rootlet, with two electron-dense
      collars and septate junction. The ciliated receptors differ in the length of the
      cilium, in the number of electron-dense collars and in the shape of sensory bulb.
      A comparison of structural features of receptors in different systematic group
      within Platyhelminthes is made.

PMID- 9602392
TI  - Molecular and immunodiagnostic investigations on bovine neosporosis in
      Switzerland.
AB  - Neospora caninum has gained considerable attention through its role in the
      aetiology of bovine abortion. Due to its close phylogenetic relationship with
      Toxoplasma gondii, respective unequivocal differential diagnosis deserves special
      consideration. In order to evaluate the diagnostic performance of molecular and
      immunodiagnostic techniques and to provide insights into the epidemiological
      significance of bovine neosporosis in Switzerland, we conducted a study on 83
      cases of bovine abortion: of these, 24 (29%) foetal brains were positive by
      Neospora-PCR, six of these foetuses were simultaneously seropositive in Neospora
      IFAT and/or somatic antigen-ELISA. Conversely, four (5%) foetal brains were
      considered positive by Toxoplasma-PCR, two of which were also seropositive in the
      Toxoplasma-P30-ELISA and/or direct agglutination test. The seroprevalence in 1689
      cattle sera obtained from 113 diary farms was 11.5% (95% confidence interval: 9.2
      13.8) by Neospora-somatic antigen-ELISA were and 10.7% (95% confidence interval:
      8.3-12.6) by Toxoplasma-P30-ELISA. From the same samples, 1.1%, less than
      statistically expected, were positive in both ELISA. Within selected groups of
      cow-calf farms, the seroprevalence determined using the Neospora-somatic antigen
      ELISA was 14% (95% confidence interval 5.0-23.0) for dams and 15% (95% confidence
      interval: 3.0-28.0) for offspring calves. Seroprevalences determined by
      Toxoplasma-P30-ELISA were 8% (95% confidence interval: 4.0-12.0) for dams and 3%
      (95% confidence interval: 0.3-6.0) for calves. None of the sera gave a positive
      reaction in both ELISA. Our data indicated that prenatal neosporosis appears as
      an important cause of bovine abortion in Switzerland.

PMID- 9602393
TI  - Lung cancer deaths in the United States from 1979 to 1992: an analysis using
      multiple-cause mortality data.
AB  - BACKGROUND: We sought to describe trends in the presence of lung cancer at the
      time of death in the United States from 1979 to 1992. METHODS: We analysed death
      certificate reports in the Multiple-Cause Mortality Files compiled by the
      National Center for Health Statistics, searching for any mention of lung cancer,
      lung cancer as the underlying cause of death, and comorbid conditions. RESULTS:
      Of the 29,042,213 decedents in the study period, 1,892,129 (6.5%) had a diagnosis
      of lung cancer listed on their death certificates; of these 1,892,129 decedents,
      1,734,767 (91.7%) had lung cancer listed as the underlying cause of death.
      Decedents with lung cancer listed as being present but not the underlying cause
      of death were more likely to be male (relative risk [RR] 1.16, 95% confidence
      interval [CI]: 1.15-1.17), and older (RR 4.61, 95% CI: 4.35-4.88 for decedents
      older than 85 compared to those aged less than 44), but less likely to be black
      than white (RR 0.88, 95% CI: 0.87-0.90). The mortality rate, age-adjusted to the
      1980 population, increased 23.0%, from 47.9 per 100,000 in 1979 to 58.9 per
      100,000 in 1992. Over the study period, black men had the highest mortality rates
      (117.3-125.2 per 100,000), followed by white men (81.7-88.7 per 100,000), men of
      other races (37.4-46.7 per 100,000), white women (22.1-39.1 per 100,000), black
      women (21.4-38.2 per 100,000), and women of other races (12.6-18.1 per 100,000).
      Age-adjusted, state specific rates varied threefold, from 30.4 per 100,000 in
      Utah to 93.9 per 100,000 in Nevada. CONCLUSIONS: We conclude that the underlying
      cause of death data base, which captures almost 92% of decedents with lung cancer
      present, accurately tracks lung cancer mortality trends in the US. Mortality
      rates of lung cancer, which are decreasing among men, continue to increase among
      women.

PMID- 9602394
TI  - Lung cancer among Chinese females in Singapore 1968-1992: time trends, dialect
      group differences and implications for aetiology.
AB  - BACKGROUND: Chinese females are distinguished internationally as having
      relatively high lung cancer incidence rates despite a low prevalence of cigarette
      smoking. In Singapore, this population comprises several dialect groups which
      have origins in different regions in China, each with its own traditional
      cultural practices. METHODS: An analysis of 4029 incident cases of the disease
      notified to the Singapore Cancer Registry for 1968-1992 was undertaken to provide
      some insight into important aetiologic factors among these women. RESULTS: The
      age-standardized incidence rate of lung cancer rose from 17.3 per 100,000 woman
      years in 1968-1972 to 23.0 in 1978-1982 before falling off in more recent years.
      Age-period-cohort analysis indicated significant period and birth cohort effects,
      with the risk being highest for women born around 1908. Between the major dialect
      groups, Cantonese women had a significantly high rate compared with Hokkiens
      (relative risk [RR] = 2.6, 95% CI: 2.4-2.8). Histologically, there appears to be
      an increase in the proportion of adenocarcinomas diagnosed over this period
      (25.8% in 1968-1972 to 51.3% in 1988-1992). CONCLUSION: Our results suggest that
      traditional practices which have decreased over the years, and are more prominent
      among Southern Chinese, may play a part in the aetiology of lung cancer locally.

PMID- 9602395
TI  - Intakes of selected foods and beverages and the incidence of gastric cancer among
      the Japanese residents of Hawaii: a prospective study.
AB  - BACKGROUND: We report on the associations between the intake of certain foods and
      beverages and the incidence of gastric cancer in a cohort of 11,907 randomly
      selected Japanese residents of Hawaii (6297 women and 5610 men). METHODS: The
      daily intake of six beverages, cigarettes and alcohol and the weekly frequency of
      intake of 13 foods and food groups was estimated with a short food frequency
      questionnaire. Over an average follow-up period of 14.8 years, 108 cases of
      gastric cancer (44 women, 64 men) were identified via linkage to the Hawaii Tumor
      Registry. RESULTS: In gender-combined proportional hazards analyses, the
      consumption of fresh fruit seven or more times per week was associated with a
      significantly reduced risk of gastric cancer, compared to lower levels of
      consumption (relative hazard (RH): 0.6, 95% confidence interval (CI): 0.4-1.0, P
      = 0.03). The combined intake of fresh fruit and raw vegetables was inversely
      associated with the risk of gastric cancer in the total cohort, and among the men
      (P < 0.05). No significant relationships were found between gastric cancer
      incidence and the intake of pickled vegetables, miso soup, dried or salted fish,
      or processed meats among either gender. Compared to non-drinkers, men who drank
      one cup of coffee per day had a significantly elevated risk of gastric cancer
      (RH: 2.5, 95% CI: 1.0-6.1, P = 0.05), but there was no evidence of a dose
      response relationship. Cigarette smoking and consumption of alcohol were not
      related to gastric cancer, in analyses restricted to the men. CONCLUSIONS: The
      results related to fruit and vegetable intake are consistent with an anti
      nitrosating effect of these foods, while the unexpected association between
      coffee consumption and gastric cancer is difficult to explain and may represent a
      chance finding.

PMID- 9602396
TI  - The prevalence of hypertension in rural and urban Cameroon.
AB  - BACKGROUND: The quickening pace of change and adoption of western lifestyles by
      people in developing countries has led to a sharp rise in the incidence of
      hypertension. Yet epidemiological studies using validated methods are rare
      especially in Central Africa. METHODS: The prevalence of hypertension, according
      to the World Health Organization definition (systolic blood pressure [SBP] > or =
      160, diastolic [DBP] > or = 95 mmHg), was estimated by a population-based survey
      in 1798 Cameroonian subjects aged 25-74 years. There were 746 individuals from a
      rural area (308 men, 438 women) and 1052 (461 men, 591 women) from an urban area.
      RESULTS: The response rate was 95% and 91% for the rural and urban populations
      respectively. The age-standardized prevalence of hypertension was significantly
      higher in the urban than in the rural area. It was 16.4% (95% CI: 11.6-21.2) in
      urban men and 12.1% (95% CI: 7.9-16.2) in urban women, while it was 5.4% (95% CI:
      2.9-8.0) in rural men and 5.9% (95% CI: 3.8-8.0) in women. Borderline
      hypertension (SBP 140-160, DBP 90-95 mmHg) was detected in 7.4% (95% CI: 4.4
      10.4) and 6.6% (3.1-10.2) of urban, and 7.3% (95% CI: 4.7-9.9) and 2.9% (95% CI:
      1.5-4.4) of rural men and women respectively. CONCLUSIONS: These results indicate
      that hypertension is still uncommon in rural Cameroon but occurs frequently in
      the urban community, reaching a proportion comparable with industrialized urban
      communities.

PMID- 9602397
TI  - Underreporting of energy, protein and potassium intake in relation to body mass
      index.
AB  - BACKGROUND: Differential underreporting of dietary intake by subgroups of body
      mass index (BMI) will confound associations between dietary intake and BMI
      related diseases. We estimated the magnitude of BMI-related underreporting for
      energy, protein, and potassium intake for the Dutch cohorts of the European
      Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: The study
      population consisted of 134 Dutch men and women, aged 21-71 years, who
      participated in a pilot of EPIC. Ratios of reported dietary intakes to biomarkers
      were used as measures for underreporting. Dietary intake was assessed by a food
      frequency questionnaire (FFQ) and repeated 24-hour dietary recalls. Biomarker for
      energy intake was calculated basal metabolic rate; for protein and potassium
      intake the biomarker was 24-hour urinary nitrogen and potassium excretion,
      respectively. The measures of underreporting were linearly regressed on BMI (in
      kg/m2). RESULTS: Significant negative regression coefficients were observed when
      regressing energy ratio on BMI with adjustment for physical activity (FFQ: beta =
      -0.04 for men, beta = -0.02 for women; 24-hour recalls: beta = -0.03 for men,
      beta = -0.04 for women). In men, a significant negative regression coefficient
      (beta = -0.03) was observed when regressing protein ratio on BMI; for the recalls
      however only after adjustment for age and education (beta = -0.02). In women,
      negative regression coefficients were also obtained, but for the FFQ only after
      exclusion of dieting women (both FFQ and 24-hour recalls: beta = -0.02).
      According to the recalls, but not the FFQ, a significant negative regression
      coefficient (beta = -0.02) was observed among women when regressing potassium
      ratio on BMI. CONCLUSIONS: In this Dutch population, BMI-dependent underreporting
      of 20-25% over the observed range of BMI is present for protein and energy,
      Further study on BMI-dependent underreporting of dietary intake in EPIC cohorts
      is warranted.

PMID- 9602398
TI  - Effects of an assessment of needs for medical and social services on long-term
      mortality: a randomized controlled study.
AB  - BACKGROUND: The aim of this study was to investigate the long-term effects of one
      general health screening on mortality. METHOD: After stratification and
      randomization of a population of 450,000 inhabitants, two groups were formed, an
      intervention group of 3064 people and a control group of 29,122 people. From the
      National Cause of Death Register, data were collected as regards death and causes
      of deaths for 1970-1990. RESULTS: Multivariate analysis was used to correct for
      known confounders. We then found no differences between the groups regarding
      deaths from all causes, cardiovascular diseases, cancer or accidents and
      poisoning. CONCLUSIONS: One general health screening seems to have little, if any
      value in preventing fatal diseases.

PMID- 9602399
TI  - The stability of lifestyle behaviour.
AB  - BACKGROUND: The stability of lifestyle behaviour has been studied over a 4-year
      period in a sample of 1400 men in The Netherlands. The influence of both
      socioeconomic status and age was studied in relation to lifestyle behaviour
      change. METHODS: Lifestyle behaviour was analysed by means of index scores, each
      covering one of four domains: smoking, alcohol consumption, physical activity and
      dietary habits. Changes in lifestyle behaviour were analysed at individual and
      group level, using different statistical methods. RESULTS: Smoking behaviour
      remained highly constant, whereas alcohol consumption had only moderate
      stability. Physical activity and dietary habits had greater variability over this
      time period. Age and socioeconomic status are related to the prevalence of
      lifestyle behaviour, whereas only age is related to the stability of lifestyle
      behaviour. Socioeconomic status did not relate to changes in lifestyle behaviour.
      CONCLUSIONS: The four lifestyle behaviours differed in the degree of variation
      over a 4-year period. Only a small group (11%) changed two or more lifestyle
      behaviours. This implies that lifestyle behaviour is not a unified concept and
      should not be treated in that way in public health campaigns.

PMID- 9602400
TI  - Examining the continuity of self-rated health.
AB  - BACKGROUND: The study examines whether self-rated health forms a continuum from
      poor through average to good health in terms of two groups of health-related
      variables. METHODS: The data come from the 1994 Finnish Survey on Living
      Conditions, a representative sample of Finnish men and women aged 25 years or
      older (n = 7290). Logistic regression analysis was used with two dependent
      variables: (1) average versus good/excellent self-rated health and (2) poor
      versus good/excellent self-rated health. Two groups of independent variables were
      used: (1) risk factors and (2) ill-health indicators. Separate analyses were made
      for men and women controlling for sociodemographic background variables. RESULTS:
      Of the risk factors, BMI and physical exercise were associated both with average
      and poor self-rated health whereas frequency of drinking was only associated with
      poor health. All used indicators of ill health were strongly associated with
      average as well as poor self-rated health. With the exception of BMI, the
      associations of both risk factors and ill health were stronger with poor than
      with average health. CONCLUSIONS: The study suggests that self-rated health forms
      a continuum from poor to good health when risk factors and indicators of ill
      health are considered, and that there are only minor differences in the
      continuity of self-rated health between men and women.

PMID- 9602401
TI  - Firearm-related deaths in the United States and 35 other high- and upper-middle
      income countries.
AB  - BACKGROUND: The Forty-Ninth World Health Assembly recently declared violence a
      worldwide public health problem. Improved understanding of cross-national
      differences is useful for identifying risk factors and may facilitate prevention
      efforts. Few cross-national studies, however, have explored firearm-related
      deaths. We compared the incidence of firearm-related deaths among 36 countries.
      METHODS: Health officials in high-income (HI) and upper-middle-income countries
      (UMI) with populations greater than one million were asked to provide data using
      ICD-9 codes on firearm-related homicides, suicides, unintentional deaths and
      deaths of undetermined intent, as well as homicides and suicides for all methods
      combined. Thirty-six (78%) of the 46 countries provided complete data. We
      compared age-adjusted rates per 100,000 for each country and pooled rates by
      income group and geographical location. RESULTS: During the one-year study
      period, 88,649 firearm deaths were reported. Overall firearm mortality rates are
      five to six times higher in HI and UMI countries in the Americas (12.72) than in
      Europe (2.17), or Oceania (2.57) and 95 times higher than in Asia (0.13). The
      rate of firearm deaths in the United States (14.24 per 100,000) exceeds that of
      its economic counterparts (1.76) eightfold and that of UMI countries (9.69) by a
      factor of 1.5. Suicide and homicide contribute equally to total firearm deaths in
      the US, but most firearm deaths are suicides (71%) in HI countries and homicides
      (72%) in UMI countries. CONCLUSIONS: Firearm death rates vary markedly throughout
      the industrialized world. Further research to identify risk factors associated
      with these variations may help improve prevention efforts.

PMID- 9602402
TI  - Morbidity differences by occupational class among men in seven European
      countries: an application of the Erikson-Goldthorpe social class scheme.
AB  - BACKGROUND: This paper describes morbidity differences according to occupational
      class among men from France, Switzerland, (West) Germany, Great Britain, the
      Netherlands, Denmark, and Sweden. METHODS: Data were obtained from national
      health interview surveys or similar surveys between 1986 and 1992. Four morbidity
      indicators were included. For each country, individual-level data on occupation
      were recorded according to one standard occupational class scheme: the Erikson
      Goldthorpe social class scheme. To describe the pattern of morbidity by
      occupational class, odds ratios (OR) were calculated for each class using the
      average of the population as a reference. The size of morbidity differences was
      summarized by the OR of two broad hierarchical classes. All OR were age-adjusted.
      RESULTS: For all countries, a lower than average prevalence of morbidity was
      found for higher and lower administrators and professionals as well as for
      routine nonmanual workers, whereas a higher than average prevalence was found for
      skilled and unskilled manual workers and agricultural workers. Self-employed men
      were in general healthier than the average population. The relative health of
      farmers differed between countries. The morbidity difference between manual
      workers and the class of administrators and professionals was approximately
      equally large in all countries. Consistently larger inequality estimates, with no
      or slightly overlapping confidence intervals, were only found for Sweden in
      comparison with Germany. CONCLUSIONS: Thanks to the use of a common social class
      scheme in each country, a high degree of comparability was achieved. The results
      suggest that morbidity differences according to occupational class among men are
      very similar between different European countries.

PMID- 9602403
TI  - Night blindness of pregnancy in rural Nepal--nutritional and health risks.
AB  - BACKGROUND: Night blindness (XN) is the most common clinical symptom of vitamin A
      deficiency among children in developing countries. Yet little is known about the
      aetiology or associated risks of maternal XN. Emerging evidence from South East
      Asia suggests that it may be more frequent than previously thought in women of
      reproductive age, especially during pregnancy. METHODS: A population-based, case
      control study was conducted to reveal the epidemiology of XN among pregnant
      Nepali women. Night blind cases were identified by history through a weekly
      community surveillance system. Controls were randomly selected from a pool of
      pregnant women without XN and pair-matched for gestational age of the cases. A
      home-based assessment was done within a week of selection, at which 7-day food
      frequency and morbidity histories were collected, anthropometry measured, and
      capillary blood drawn for serum retinol, beta-carotene and haemoglobin (Hb)
      estimation. RESULTS: Cases and controls did not differ by age or number of
      previous pregnancies. However, cases were more likely to be from the lower
      castes, be illiterate, live in poorer quality homes, and own no land. The mean
      serum retinol level of cases was approximately 0.30 mumol/l lower than controls
      (P < 0.001), indicating a low vitamin A status of night blind pregnant women.
      Mean Hb level was significantly lower (by 0.7 g/dl, P < 0.004), and the risk of
      severe anaemia (Hb < 7.0 g/dl) higher among cases than controls (odds ratio =
      3.0, 95% CI: 1.25-7.23). Cases were more under-nourished than controls reflected
      by lower mean weight (-2.6 kg), body mass index (-0.8), arm circumference (-0.9
      cm) and triceps skinfold (-0.8 mm). Night blindness was associated with less
      frequent consumption of preformed vitamin A (milk products, fish and meat) and
      provitamin A (dark green leafy vegetables and mangoes) foods, especially in
      summer. Night blind women were 2-3 times more likely to report symptoms of
      urinary/reproductive tract infections such as lower abdominal pain, painful and
      burning urination, or vaginal discharge, symptoms of diarrhoea/dysentery, of pre
      eclampsia or eclampsia, and of nausea, vomiting or poor appetite throughout
      pregnancy than controls. CONCLUSION: Women who experience XN during pregnancy
      have a low vitamin A status, although several other risk factors appear to
      cluster among these women as well. Night blind women are also more likely to be
      anaemic, ill, and acutely under-nourished, and to be consuming a nutritionally
      poorer diet in pregnancy than non-night blind pregnant women. A simple history of
      XN can identify women at high risk during pregnancy who may require special
      nutritional support, antenatal care and counselling.

PMID- 9602404
TI  - Smoking, intra-uterine growth retardation and sudden infant death syndrome.
AB  - BACKGROUND: Sudden infant death syndrome (SIDS) is associated with factors such
      as maternal smoking and low birthweight, which may be linked causally. Recent
      pathological studies have shown evidence for growth retardation at organ level in
      SIDS infants whose weights at birth were above the tenth centile, and were not
      therefore recognized as growth retarded clinically. It might be of value to
      identify such hidden growth retardation at birth, and to have an estimate of how
      much of it may be associated with maternal cigarette smoking. METHODS: 104 SIDS
      victims who died between 1987 and 1992 and who were brought to a single
      children's hospital, were compared to 206 controls, matched for place and date of
      birth. Birthweight, occipitofrontal head circumference, maternal age, and smoking
      habit, and height and weight at booking were recorded. Birthweight ratio (BWR),
      head circumference ratio (OFCR), and a growth retardation ratio (GRR = OFCR/BWR)
      were computed for each infant. RESULTS: No significant differences were seen
      between SIDS and control groups for BWR. OFCR or GRR. Separating smoking mothers
      from non-smokers in both groups showed significant growth retardation in smokers'
      children. SIDS infants of non-smokers as a group were not growth retarded, but
      had a lower gestational age at birth. Logistic regression analysis showed SIDS to
      be significantly related to gestation (OR 0.86/week) and smoking (OR 4.8), but
      not independently to BWR, maternal age or maternal body mass index (MBMI).
      CONCLUSION: Most of the risk of SIDS associated with growth retardation may be
      accounted for by maternal smoking.

PMID- 9602405
TI  - Length and ponderal index at birth: associations with mortality,
      hospitalizations, development and post-natal growth in Brazilian infants.
AB  - BACKGROUND: Low birthweight infants suffer greater mortality and neonatal
      morbidity, grow less well in infancy and show poorer psycho-motor development.
      However, this simple categorization may obscure important differences in
      aetiology and prognosis between infants born stunted, thin, or both. METHODS: In
      1993, all births in Pelotas, Brazil, were enrolled into a prospective study of
      health and development in infancy. Of 5249 live births, 5160 had length and
      weight measures at birth, and were classified into tertiles of length and
      ponderal index. All deaths and hospitalizations were monitored, and suspected
      developmental delay and attained growth at 12 months were assessed on a subsample
      of 1364 infants. Logistic regression was used to control for gestational age and
      socioeconomic status. RESULTS: There was no association between birth length and
      ponderal index tertiles. After adjusting for gestational age, infants in the
      lower tertiles of both length and ponderal index presented a 3.8-times higher
      risk of mortality from day 8 to day 365, and a 2.5-times higher risk of
      hospitalization compared to infants with greater birth lengths and/or ponderal
      indices. Suspected developmental delay was associated with length and, less
      strongly, with ponderal index, but there was no synergism between the two.
      Infants in the middle and upper tertiles of ponderal index at birth became
      thinner. CONCLUSIONS: Birth length was strongly associated with development at 12
      months, but only infants born both short and thin were at increased risk of
      mortality and hospitalizations. The combination of the two measures provides a
      useful classification of the anthropometric status of the newborn.

PMID- 9602406
TI  - Familial patterns in birth characteristics: impact on individual and population
      risks.
AB  - BACKGROUND: Familial patterns in reproductive outcome have been suggested
      previously, but few studies have comprehensively evaluated both length of
      gestation and types of growth retardation. METHODS: Information on intrauterine
      period and birth characteristics for a cohort of Swedish women born 1955-1972 was
      linked with information on these women's own reproductive experiences during 1973
      1990. Familial trends in preterm deliveries, small-for-gestational age (SGA)
      births and two types of growth retardation were evaluated for mothers relative to
      their own birth characteristics (n = 4746), relative to their older sisters'
      deliveries (n = 2931) and among consecutive deliveries of the mothers (n =
      14,209). Adjusted relative risks (RR) were calculated from logistic regression
      analyses. RESULTS: Mothers who had themselves been preterm at birth were not at
      increased risk of any of the outcomes studied. Mothers who had themselves been
      SGA at birth had an almost 50% higher risk (NS) of giving birth to either a
      preterm or an SGA infant than had mothers who had not been SGA at birth. Mothers
      tended to repeat the same patterns in subsequent deliveries: RR was 3.7 for a
      second preterm delivery given a previous one and 7.8 for a second SGA delivery
      given a previous one. Among SGA siblings, chronic growth retardation was more
      often repeated than was acute growth retardation. Mothers with an older sister
      who had given birth to a preterm infant had an 80% higher risk of giving birth to
      a preterm infant. CONCLUSIONS: Familial trends in gestational age and body
      proportions at birth were demonstrated; however, the relatively small population
      attributable risk per cents in Sweden are discussed.

PMID- 9602407
TI  - A longitudinal study of prolonged breastfeeding in relation to child
      undernutrition.
AB  - BACKGROUND: In a number of studies prolonged breastfeeding was associated with a
      higher risk of undernutrition, although most of these studies are limited by
      their cross-sectional design which does not allow examination of temporal
      relationships between full weaning and undernutrition. METHODS: The relationship
      between prolonged breastfeeding and child growth was examined prospectively among
      children under 36 months old who participated in a large cohort study. At
      baseline and at each of three 6-monthly follow-up visits breastfeeding status was
      assessed and all subjects were weighed and measured. RESULTS: Undernourished
      children were more likely to be breastfed for a longer period of time compared
      with normal children. We found a small difference between breastfed and fully
      weaned children in the gain in height over the following 6-month period; however,
      breastfed children were likely to gain significantly less weight, particularly
      among children who were aged 6-12 months. Similar findings were noted when these
      associations were examined among children who were normally nourished at the time
      of breastfeeding assessment. The inverse association between breastfeeding status
      and weight gain was significantly larger among children of poor or illiterate
      mothers compared with children of relatively more affluent or literate mothers,
      respectively. CONCLUSIONS: Our findings suggest that the inverse association is
      not causal, and may be explained by poorer complementary feeding among breastfed
      compared with weaned children. Children from poorer households and whose parents
      are illiterate are more likely to have less than adequate complementary feeding.
      The importance of adequate complementary feeding in the second half of infancy
      needs to be stressed in nutrition education programmes.

PMID- 9602408
TI  - Associations between diagnoses, impairments, disability and handicap in a
      population of elderly people.
AB  - BACKGROUND: 'Handicap' is the disadvantage for an individual that results from
      ill-health. It represents an important outcome in chronic disabling disease, but
      has proved difficult to measure until recently. The strength of association
      between handicap and other health status measures, and the relative contributions
      of health and socioeconomic variables to handicap have not been studied
      previously. METHODS: We undertook a cross-sectional survey of all people > 65
      years old in a defined geographical area of North London. The interview was based
      on the short-CARE psychiatric survey tool, and in addition included measures of
      physical health and disability, the London Handicap Scale, income, social support
      and housing. In all, 654 residents (74%) from a register of 889 were interviewed.
      A random sample of 225 had additional data collected which are reported in this
      analysis. RESULTS: Strength of association with handicap scores increased
      progressively from diagnosis to impairment to disability. Variation in handicap
      with diagnosis was explained by impairment, and variation with impairment was
      mostly explained by disability. Age, housing quality, social support and income
      were associated with handicap score, but confounding by these did not explain the
      association between handicap and other aspects of disablement. Disease-associated
      variables explained quantitatively much more variation in handicap than
      socioeconomic variables. CONCLUSIONS: The most potent influences on handicap are
      disease and disability, justifying the high priority given by health services to
      detection, treatment and rehabilitation. Where this is not possible handicap may
      be reduced to some extent through socioeconomic intervention.

PMID- 9602409
TI  - Intra- and inter-rater agreement in the assessment of occupational exposure to
      metals.
AB  - BACKGROUND: Among the methods of retrospective occupational exposure assessment,
      expert review is considered the most accurate. Although expert review provides a
      more objective measure of exposure, depending on the exposure of interest it may
      still result in a significant degree of misclassification. METHODS: To evaluate
      the reliability in occupational metal exposure assessment by expert review, we
      analysed job history data from a case-control study of a neurological disease.
      First, one industrial hygienist (IH) did an initial exposure assessment of the
      metals copper, iron and lead, blinded to case-control status, for 608 subjects
      who had 3033 total jobs. We then compared exposure assessments from the original
      review with a second blinded review of 60 job histories (306 jobs) by the same IH
      (intra-rater) and of 64 job histories (361 jobs) by a different IH (inter-rater).
      RESULTS: The per cent agreements for the intra-IH comparisons were 89.6 for
      copper, 87.9 for iron and 94.6 for lead, whereas the inter-IH per cent agreements
      were 86.4 for copper, 81.1 for iron and 76.2 for lead. Based on the assumption
      that reliability is related to validity, we calculated an estimate of
      misclassification of metal exposure by one IH. Our exposure misclassification
      estimates show a sizable attenuation of the odds ratio, with the expected bias
      similar for copper and iron when using either intra- or inter-reliability results
      to estimate misclassification. CONCLUSION: Our results suggest that variation in
      the expert assessment of metal exposure is due mainly to the difficulties
      involved in transforming an occupational history into an estimate of exposure.

PMID- 9602410
TI  - End-stage renal disease projections for Canada to 2005 using Poisson and Markov
      models.
AB  - BACKGROUND: End-stage renal disease (ESRD) incidence and prevalence are
      increasing in many countries worldwide. Due to the high cost of therapy,
      predicting future numbers of patients requiring dialysis and transplantation is
      necessary for health care planners. Projecting therapy-specific chronic disease
      prevalence is inherently problematic, and examples of suitable models and their
      application are sparse. When applied, rarely was the adequacy of such models
      evaluated. METHODS: We describe and illustrate a method for projecting therapy
      specific ESRD prevalence in Canada for 1995-2005 using data obtained from the
      Canadian Organ Replacement Register. The projections combine the Poisson model
      for incidence rates and a Markov model for patient follow-up. Model adequacy is
      empirically validated by data-splitting. RESULTS: Large increases in ESRD
      prevalence are expected in Canada, with an average annual increase of 6.9%
      projected for 1995-2005. Upon validation, the projection model based on 1981-1987
      data was able to predict 1994 prevalence within 1%, while projected therapy
      specific prevalences closely approximated those observed. CONCLUSIONS: Therapy
      specific ESRD prevalence was successfully projected using Poisson and Markov
      models. Where multistate prevalence forecasts are required, the method could be
      augmented for application to various other chronic diseases.

PMID- 9602411
TI  - Multivariate time series analysis in nosocomial infection surveillance: a case
      study.
AB  - BACKGROUND: The present study describes the use of time series analysis in the
      evaluation of the incidence of nosocomial infection. The main hypothesis analysed
      was that monthly occurrence of nosocomial infection in a hospital may be related
      to work-related factors such as the control and training of personnel imposed by
      a surveillance system, strikes supported by medical personnel and movement of
      personnel. Time series analysis was used to quantify, model and statistically
      evaluate these interventions. METHODS: The data employed (March 1982-December
      1990) were supplied by the nosocomial infection surveillance system of a primary
      care general hospital. The monthly time series incidence of nosocomial infections
      (measured as percentage cumulative incidence) was analysed by curve fitting,
      autoregressive, integrated and moving average (ARIMA) modelling (Box-Jenkins) and
      intervention and dynamic regression analysis. RESULTS: The imposed control and
      training of personnel by the surveillance system was associated with a 3.63%
      decrease in the accumulated monthly incidence of nosocomial infection from 7.82%
      to a baseline level of 4.19%. There was a strong indication that an increase of
      infection incidence of 4.34% corresponded to a medical strike. This increase was
      maintained over the following months raising the baseline level to 4.84%. An
      increase of 0.18% was associated with each new nursing contract. Evidence was
      obtained for the possible relationship between incidence of nosocomial infection
      and vacation periods. CONCLUSIONS: The results suggest the need for strict
      control of the activities of hospital personnel and for the adoption of certain
      preventative measures during vacation periods to avoid an undesirable increase in
      the incidence of nosocomial infections.

PMID- 9602413
TI  - Is there an interaction between human immunodeficiency virus and Plasmodium
      falciparum?
AB  - BACKGROUND: There is a potential for interaction between malaria and human
      immunodeficiency virus (HIV) infection. HIV infection might reduce immunity to
      malaria resulting in more frequent and severe infections; conversely malaria
      might enhance the progression of HIV infection to AIDS. In this paper we have
      reviewed some of the studies that have addressed this topic. METHODS: Studies
      identified by a MEDLINE search were systematically reviewed and the measures of
      association between the two infections were either abstracted or recalculated
      from the reported data. Inferences drawn from these studies and the biological
      plausibility of an interaction are discussed. RESULTS: The prevalence ratio (PR)
      of peripheral parasitaemia among HIV seropositive (HIVSP) individuals compared to
      HIV seronegative (HIVSN) individuals ranged from 0.72 to 0.94 in children and
      from 3.3 to 0.69 in adults. However, only one study showed a statistically
      significant difference between HIVSP and HIVSN groups (PR 3.3, 95% CI: 2.7-4.2).
      The rate ratio of non-severe malaria among HIVSP children compared to HIVSN
      children was 1.4 (95% CI: 0.99-2.0). Data from a trial of chemoprophylaxis during
      pregnancy suggested that placental malaria may predispose to perinatal
      transmission of HIV. Studies that have investigated the immune response to P.
      falciparum among HIVSP subjects have given variable results. CONCLUSION: There is
      no convincing evidence for an interaction between malaria and HIV with the
      possible exception of an interaction between placental malaria and HIV infection.
      Several studies, however, had potentials for bias and/or an inadequate sample
      size. There is a need for carefully designed studies to resolve whether mortality
      from severe malaria, in particular cerebral malaria, is increased in HIVSP
      subjects, whether malaria infection of the placenta increases the risk of
      vertical transmission of HIV, and whether malaria infection increases the
      progression of HIV infection to AIDS.

PMID- 9602412
TI  - Clinical and immunological features of human immunodeficiency virus infection in
      patients from Bangkok, Thailand.
AB  - BACKGROUND: To assess the association between the CD4 count and clinical diseases
      in a cohort of Thai patients. METHODS: In all, 1902 patients who presented with
      human immunodeficiency virus (HIV) infection at the Chulalongkorn University
      Hospital in Bangkok were investigated. RESULTS: At the time of presentation 295
      (15.5%) patients had acquired immunodeficiency syndrome (AIDS) and there was a
      highly significant tendency for lower CD4 counts in this group (median 67/mm3)
      than in patients free of AIDS (median 369/mm3). A total of 757 patients had data
      available on follow-up and were free of AIDS at the first visit. During a median
      follow-up of 0.9 years, 110 developed AIDS or AIDS-related death (12.2/100 person
      years). Subjects with CD4 count < 200/mm3 at initial visit showed over a ninefold
      increase in risk of developing AIDS compared to subjects with levels > or =
      500/mm3 (relative risk [RR] = 9.1; 95% CI: 5.4-16.0). The rate/100 person years
      was 47.1 compared with 6.0 in subjects with levels > or = 500/mm3. After
      adjusting for initial CD4 count, homosexual men showed over a twofold increase in
      risk of developing AIDS compared to heterosexuals (RR = 2.4; 95% CI: 1.6-4.4) and
      intravenous drug users (IVDU) showed nearly a twofold increase (RR = 1.8; 95% CI:
      0.9-3.9). The increased risk in homosexual men persisted even after further
      adjustment for clinical stage (RR = 2.2; 95% CI: 1.3-3.7) but the increased risk
      in IVDU was attenuated (RR = 1.5; 95% CI: 0.7-3.2) although it remained increased
      albeit non-significantly. Men tended to progress faster to AIDS than women but
      the difference was not significant. However, the faster progression in homosexual
      men was seen even when compared to heterosexual men only. CONCLUSION: The rate of
      progression of AIDS according to CD4 count group at baseline in this Thai cohort
      is broadly comparable with Western cohorts. It appears that heterosexuals in
      Thailand show slower progression to AIDS than homosexual men.

PMID- 9602414
TI  - New needle and syringe use, and use of needle exchange programmes by street
      recruited injection drug users in 1993.
AB  - BACKGROUND: Needle exchange programmes (NEP) provide injection drug users (IDU)
      with sterile injection equipment and receive used needles in exchange. In this
      paper we describe the use of new syringes and NEP by IDU and characteristics
      associated with using NEP in 1993. METHODS: Street-recruited IDU were interviewed
      in five US locations: Atlanta, Philadelphia, Chicago, New York City, and Los
      Angeles (LA) county. RESULTS: Most (75-95%) reported it was easy to get a new
      syringe and for their last injection, 45-77% used a new syringe and 2-18% used a
      syringe previously used by another IDU. Use of NEP ranged from 8% to 16% in
      Chicago, Philadelphia, and LA County. In LA County not having injected
      'speedball' in the last 30 days, last injection with a new syringe, and reporting
      it was very easy to get a new syringe were associated with NEP use. In
      Philadelphia, NEP use was associated with 'speedball' injection in the last 30
      days, and in Chicago, not injecting with 'speedball' and injecting with cocaine
      were associated with NEP use. CONCLUSIONS: In 1993, most street-recruited IDU in
      Chicago, Philadelphia, and LA County had not used NEP. Factors associated with
      NEP use were not consistent across sites. Dispersion of NEP and removal of legal
      barriers restricting access to sterile syringes may be more important in
      increasing the use of sterile syringes and NEP than client characteristics.

PMID- 9602415
TI  - Risk of gastroenteritis among triathletes in relation to faecal pollution of
      fresh waters.
AB  - BACKGROUND: We conducted a prospective cohort study among endurance athletes to
      investigate the effects of microbiological water quality on the risk of
      gastroenteritis after bathing in fresh waters that meet current water quality
      standards. We aimed to establish quantitative relationships, in order to evaluate
      current bathing water standards. METHODS: The study was spread over two summers,
      during which 827 triathletes (swimmers) in seven Olympic distance triathlons and
      773 participants in 15 run-bike-runs (non-swimming controls) participated.
      Intensive water quality monitoring was used to assess exposure to faecal
      indicator organisms and detailed questionnaires were used to collect data on the
      occurrence of health complaints and potential confounding factors. RESULTS: The
      microbiological water quality at the time of the triathlons met current Dutch and
      European bathing water standards. Dependent on the case definition studied,
      gastroenteritis developed in 0.4-5.2% of swimmers and 0.1-2.1% of non-swimmers in
      the week following exposure (odds ratio [OR] = 1.6-2.3). Attack rates and burden
      of disease varied with the case definition used. Among swimmers, the attack rate
      of gastroenteritis was significantly increased when the geometric mean
      concentration of thermotolerant coliforms in the water at the time of exposure
      was > or = 220/100 ml or the geometric mean concentration of Escherichia coli was
      > or = 355/100 ml (OR comparing high versus low exposure 2.9-4.7 dependent on the
      case definition studied). Thermotolerant coliform concentrations at these
      triathlons ranged from 100/100 ml (the EU guide level) to 960/100 ml (the EU
      imperative level is 2000/100 ml). Below the threshold levels attack rates were
      comparable with attack rates among non-swimmers. A relation with other indicators
      of faecal pollution was not observed. CONCLUSIONS: We observed that swimming in
      fresh waters that met the European imperative level for thermotolerant coliforms
      but failed the European guide level was associated with a significant risk of
      gastroenteritis among triathletes. This means that the current European
      imperative level for thermotolerant coliforms provides insufficient protection to
      gastrointestinal illness for those who are comparable with triathletes.

PMID- 9602416
TI  - Hepatitis B vaccination and reduced risk of primary liver cancer among male
      adults: a cohort study in Korea.
AB  - BACKGROUND: Primary liver cancer is an important health problem in Korea, where
      hepatitis B virus (HBV) infection is prevalent. The authors conducted a
      prospective cohort study to evaluate the protective effect of HBV vaccination
      against liver cancer in adults. METHODS: A total of 370,285 males aged > or = 30
      comprised the study population. They were clinically free of liver diseases, and
      had not been vaccinated against HBV at enrolment. The results of HBV surface
      antigen (HBsAg) and antibody to HBsAg (anti-HBs) marker positivity and those of
      the vaccination programme which took place during 1985 were used for the
      construction of the cohort. About 5% (n = 18,914) were HBsAg positive, 78,094
      were anti-HBs positive, and 273,277 were negative for both. Among the candidates
      for HBV vaccination (n = 273,277), 35,934 (13.2%) people had been vaccinated
      against HBV during 1985. Cases of liver cancer were ascertained by record linkage
      and from medical records covering 1986-1989. A multivariate log-linear model was
      used to test statistical significance and to estimate relative risks (RR).
      RESULTS: The total follow-up period was 1,404,566 person-years, with an average
      of 3 years and 10 months. A total of 302 incident cases were ascertained. The
      overall incidence rate of liver cancer was 21.7 per 100,000 person-years. With
      reference to the incidence level among the unvaccinated and uninfected, the RR of
      primary liver cancer among the chronically infected and that of the unvaccinated
      and infected was 18.1 (95% CI: 14.2-22.9) and 0.34 (95% CI: 0.19-0.60),
      respectively. The RR among the vaccinated group was 0.58 (95% CI: 0.31-1.09).
      CONCLUSIONS: This study suggested that artificial immunization through HBV
      vaccination, even in adulthood, reduces the risk of liver cancer. It might also
      offer a practicable means of primary prevention, especially in areas with
      hyperendemicity of HBV infection.

PMID- 9602417
TI  - Assessing hepatitis A virus epidemic stochastic process in eight cities in China
      in 1990.
AB  - BACKGROUND: In The People's Republic of China in 1990, the age-specific
      seroprevalence of hepatitis A was investigated in eight large cities. METHODS: A
      stochastic model, the two-state Markov chain, was applied to hepatitis A virus
      seroprevalence data by age group. An age-specific risk rate, Markov Risk Rate
      (MRR), and its weighted sum, Total MRR, are defined and used as novel measure
      indices to prioritize age groups for allocating vaccine or to decide in which
      cities vaccine should be used to prevent hepatitis A. RESULTS: In 1990, the MRR1-
      in Xi'an, Jinan, Ha'erbin and Huhehaote, and the MRR10- in Chongqing were over
      40. The MRR10- in Xi'an, Nanjing, Jinan and Ha'erbin and the MRR20- in Chongqing
      and Nanjing were over 20. The Total MRR in Chongqing and Ha'erbin were over 160,
      which was higher than the warning value. CONCLUSIONS: All age groups whose MRR
      was over 20 are strongly recommended to be vaccinated first. Chongqing and
      Ha'erbin are cities at high risk of a hepatitis A virus epidemic in the 1990s and
      therefore should be under close surveillance.

PMID- 9602418
TI  - An analysis of the geographical distribution of severe malaria in children in
      Kilifi District, Kenya.
AB  - BACKGROUND: Although malaria is known to be a major cause of child mortality and
      morbidity throughout sub-Saharan Africa there are few detailed studies of malaria
      mortality rates and incidence of severe malarial disease in defined communities.
      We have studied the geographical pattern of admissions to hospital with severe
      malaria and the stability of this pattern over time in Kilifi District on the
      Kenyan Coast. METHODS: Over a 2-year period all children under 5 years of age
      with severe malaria admitted to the district hospital and living in a rural study
      population of about 50,000 people were identified. Annual censuses were carried
      out in the study area, and all households were mapped using a hand-held satellite
      navigation system. The resulting databases were linked using a geographical
      information system (GIS). RESULTS: Using methods originally developed for the
      study of the geographical distribution of childhood leukaemia we assessed the
      spatial pattern of hospital admission rates for severe malaria. As expected,
      admission rates were significantly higher in children with easier access to the
      hospital. For example, those living more than 25 km from the hospital had
      admission rates which were about one-fifth of those for children living within 5
      km of the hospital. Those living more than 2.5 km from the nearest road had
      admission rates that were about half of those for children living within 0.5 km
      of a road. We also investigated short-term local fluctuations in severe malaria
      and found evidence of space-time clustering of severe malaria. CONCLUSIONS:
      Hospital admission rates for severe malaria are higher in households with better
      access to hospital than in those further away. The finding of space-time clusters
      of severe malaria suggests that it would be of value to conduct case-control
      studies of environmental, genetic and human behavioural factors involved in the
      aetiology of the disease.

PMID- 9602419
TI  - Are there national risk factors for epidemic cholera? The correlation between
      socioeconomic and demographic indices and cholera incidence in Latin America.
AB  - BACKGROUND: From 1991 through 1995, all Latin American countries maintained
      cholera surveillance systems to track the epidemic that entered the region
      through Peru in January 1991. These data were used to assess correlations between
      socioeconomic and demographic indices that might serve as national risk
      predictors for epidemic cholera in Latin America. METHODS: Correlations between
      country-specific cumulative cholera incidence rates from 1991 through 1995 and
      infant mortality, the Human Development Index [HDI] a numerical value based on
      life expectancy, education, and income), gross national product (GNP) per capita,
      and female literacy were tested using the Pearson correlation coefficient.
      RESULTS: A total of 1,339,834 cholera cases with a cumulative incidence rate of
      183 per 100,000 population were reported from affected Western Hemisphere
      countries from 1991 through 1995. Infant mortality rates were the most strongly
      correlated with cumulative cholera incidence based on the Pearson correlation
      coefficient. The HDI had a less strong negative correlation with cumulative
      cholera incidence. The GNP per capita and female literacy rates were weakly and
      negatively correlated with cholera cumulative incidence rates. CONCLUSIONS:
      Infant mortality and possibly the HDI may be useful indirect indices of the risk
      of sustained transmission of cholera within a Latin American country. Cumulative
      cholera incidence is decreased particularly in countries with infant mortality
      below 40 per 1000 live births. The lack of reported cholera cases in Uruguay and
      the Caribbean may reflect a low risk for ongoing transmission, consistent with
      socioeconomic and demographic indices. Cholera surveillance remains an important
      instrument for determining cholera trends within individual countries and
      regions.

PMID- 9602420
TI  - Measurement of physical activity exposure.

PMID- 9602421
TI  - The statistics of synergism.
AB  - Biological scientists often want to determine whether two agents or events, for
      example, extracellular stimuli and/or intracellular signaling pathways, act
      synergistically when eliciting a biological response. When setting out to study
      whether two experimental treatments act synergistically, most biologists design
      the correct experiment--they administer four treatment combinations consisting of
      (1) the first treatment alone, (2) the second treatment alone, (3) both
      treatments together, and (4) neither treatment (i.e. the control). Many
      biologists are less clear about the correct statistical approach to determining
      whether the data collected in such an experimental design support a conclusion
      regarding synergism, or lack thereof. The non-additivity of two experimental
      treatments that is central to the definition of synergism leads to an algebraic
      formulation corresponding to the statistical null hypothesis appropriate for
      testing whether or not there is synergism. The resulting complex contrast among
      the four treatment group means is identical to the interaction effect tested in a
      two-way analysis of variance (ANOVA). This should not be surprising, because
      synergism, by definition, occurs when two treatments interact, rather than act
      independently, to influence a biological response. Hence, in the most readily
      implemented approach, the correct statistical analysis of a question of synergism
      is based on testing the interaction effect in a two-way ANOVA. This review
      presents the rationale for this correct approach to analysing data when the
      question is of synergism, and applies this approach to a recent published
      example. In addition, a common incorrect approach to analysing data with regards
      to synergism is presented. Finally, several associated statistical issues with
      regard to correctly implementing a two-way ANOVA are discussed.

PMID- 9602422
TI  - Co-localization of the cysteine protease caspase-3 with apoptotic myocytes after
      in vivo myocardial ischemia and reperfusion in the rat.
AB  - The aim of our study was to characterize the temporal relationship of apoptosis
      to regional myocardial ischemia and reperfusion and we aimed to determine the
      effect of ischemia and reperfusion on the distribution of the pro-apoptotic
      cysteine protease caspase-3 (CPP 32, apopain, Yama) in an in vivo rat model. Male
      Sprague-Dawley rats (250-400 g) were anesthetized with sodium pentobarbital (65
      mg/kg, i.p.), the left external carotid artery was isolated to monitor arterial
      pressure and a left thoracotomy was performed. Regional myocardial ischemia was
      induced by occluding the left main coronary artery for 45 min. The heart was
      reperfused for 0, 60, 120 or 180 min. TUNEL staining of formalin-fixed, paraffin
      embedded left ventricle, and DNA fragmentation analysis, showed that apoptosis
      occurred during 45 min of ischemia alone, but further developed during the 3-h
      reperfusion period. Immunohistochemical analysis of ischemic/reperfused left
      ventricle showed caspase-3 levels were substantially elevated and localized in
      the ischemic/reperfused region, and that caspase-3 co-localized to TUNEL positive
      myocytes. Therefore, regional myocardial ischemia serves as a stimulus for
      myocyte apoptosis, and this form of cell death progresses time-dependently after
      the onset of reperfusion. Our studies implicate caspase-3 to be involved in
      apoptotic cell death in ischemic/reperfused rat heart.

PMID- 9602423
TI  - Calcium content of the sarcoplasmic reticulum in isolated ventricular myocytes
      from patients with terminal heart failure.
AB  - Systolic [Ca2+]i-transients have been shown to be depressed in isolated
      ventricular myocytes from patients with terminal heart failure compared to
      controls. Experiments were performed in human ventricular cells to investigate
      whether this reduced systolic [Ca2+]i-transient may be due to a decreased Ca(2+)
      content of the sarcoplasmic reticulum (SR). Single myocytes were isolated from
      left ventricular myocardium of patients with terminal heart failure undergoing
      cardiac transplantation. These results were compared to those obtained from cells
      of healthy donor hearts that were not suitable for transplantation for technical
      reasons. [Ca2+]i-transients were recorded from isolated cells under voltage clamp
      perfused internally with the Ca(2+)-indicator fura-2. The Ca(2+)-content of the
      SR was estimated by rapid extracellular application of caffeine (10 mM) to open
      the Ca(2+)-release channel of the SR and comparison of the caffeine-induced
      [Ca2+]i-transients in cells from patients with heart failure and from controls
      without heart failure. Upon steady-state depolarizations to +10 mV (maximum of
      the Ca(2+)-current), [Ca2+]i-transients in cells from patients with heart failure
      were significantly smaller than in myocytes from undiseased hearts (333 +/- 26 v
      596 +/- 80 nM, P < 0.05). Application of caffeine caused a [Ca2+]i-transient that
      was always larger than during depolarization. Caffeine-induced [Ca2+]i-transients
      were significantly smaller in cells from diseased hearts compared with controls
      (970 +/- 129 v 2586 +/- 288 nM, P < 0.01). A positive correlation was found
      between left ventricular ejection fraction and caffeine-induced [Ca2+]i
      transients in these cells. It is concluded, that depressed [Ca2+]i-transients in
      myocytes from patients with heart failure may be caused by a decreased Ca(2+)
      content of the SR possibly due to an altered Ca(2+)-ATPase activity in these
      hearts. It is not necessary to postulate an additional defect of the Ca(2+)
      release function of the SR to account for the alterations of intracellular
      (Ca2+]i-handling.

PMID- 9602424
TI  - Angiotensin II activates Stat5 through Jak2 kinase in cardiac myocytes.
AB  - Angiotensin II (Ang II) treatment was recently shown to activate Jak2, Stat1, and
      Stat3 proteins in cardiac myocytes. Angiotensin-converting enzyme (ACE)
      inhibitors have been shown to be an effective clinical treatment following
      myocardial infarction, implying that inhibition of Ang II production is
      beneficial in this pathological condition. Some of the effects of Ang II in
      cardiac myocytes may be mediated by the JAK-STAT signaling pathway. The AT1
      receptor was the first G-protein-coupled-receptor reported to activate the JAK
      STAT pathway. Recently, however, another G-protein-coupled-receptor (i.e.
      serotonin) was also shown to signal through the JaK2 and STAT proteins in
      myoblasts. We hypothesized that Ang II treatment might also activate Stat5
      transcription factors in cardiac myocytes. In this study, we provide evidence
      that the G-protein-coupled, Ang II type I (AT1) receptor couples to activation of
      Stat5 through Jak2 kinase in neonatal rat ventricular myocytes. Angiotensin II
      induces a 1.5- to 10-fold increase in a Stat5 transcription complex, which binds
      to the prolactin-inducing element (PIE). By Western analysis, Stat5 protein
      levels were shown to be tyrosine phosphorylated two- to three-fold over control,
      following. Ang II treatment of cardiac myocytes. Phosphorylation of Stat5a and
      Stat5b proteins was rapid and sustained (30-60 min), and Jak2 kinase co
      immunoprecipitated with activated Stat5 proteins. In cardiac myocytes, Stat5
      proteins co-immunoprecipitated with the AT1 receptor. Selective inhibition of
      Jak2 kinase with AG-490 blocked formation of prolactin-inducing factor (PIF)
      complexes by Ang II, suggesting that Jak2 kinase was required for the tyrosine
      phosphorylation of Stat5 in cardiac myocytes.

PMID- 9602425
TI  - Influence of pHi and creatine phosphate on alpha-adrenoceptor-mediated cardiac
      hypertrophy.
AB  - Stimulation of alpha-adrenoceptors on ventricular cardiomyocytes isolated from
      adult rat hearts leads to cellular alkalization, increases of creatine phosphate
      concentration, RNA mass, and protein synthesis. This study investigated whether
      the increase of creatine phosphate concentrations is causally linked to the
      hypertrophic response of cardiomyocytes under alpha-adrenoceptor stimulation.
      Cellular alkalization achieved with phenylephrine (10 microM), an alpha
      adrenoceptor agonist, was abolished in the presence of the sodium-proton-exchange
      (NHE)-inhibitor HOE 694 (1 microM). HOE 694 inhibited also the alpha-adrenoceptor
      mediated increase in cellular creatine phosphate and the increase in cellular RNA
      mass. The phenylephrine-induced stimulation of protein synthesis (determined by
      incorporation of 14C-phenylalanine) was reduced by one-third when HOE 694 was
      present. beta-Guanidinopropionic acid was added to cardiomyocytes to reduce
      cellular creatine phosphate concentrations. In these cultures, alpha-adrenoceptor
      stimulation activated NHE, but creatine phosphate concentrations were not
      increased. Protein synthesis was augmented to the same extent as in control
      cultures, but total RNA mass did not increase. From these results we conclude
      that alpha-adrenoceptor stimulation causes the increase in protein synthesis via
      activation of NHE, but independent of the concomitant increase in creatine
      phosphate contents. The effect of alpha-adrenoceptor stimulation on total RNA
      mass (translational capacity) is also caused by NHE activation, but depends on
      the changes in creatine phosphate contents as well.

PMID- 9602427
TI  - Propafenone inhibition of human atrial myocyte repolarizing currents.
AB  - This study was aimed at defining cellular electropharmacologic effects of
      propafenone on repolarizing currents in human atrial myocytes. Whole-cell patch
      clamp of enzymatically isolated atrial myocytes from 11 cardiac surgical patients
      aged between 29 days and 74 years revealed potent time- and concentration
      dependent (IC50 = 4.8 +/- 0.4 mumol/l), but age-, voltage-, and frequency
      independent propafenone inhibition of transient outward current. Time course of
      apparent transient outward current inactivation was best described by a single
      exponential process in the absence of propafenone and by a double exponential
      model in its presence, with drug-concentration-dependent acceleration of the fast
      exponential component. Neither voltage dependence of steady-state transient
      outward current inactivation nor time course of recovery from inactivation was
      affected by propafenone. Significant inhibition (P < 0.05) of the ultra-rapidly
      activating delayed rectifier and inwardly rectifying currents was observed only
      in the presence of > or = 10 mumol/l propafenone. These actions of propafenone
      could explain its repolarization prolonging effect and might contribute to
      clinical electrophysiologic responses which have been documented in patients of
      all ages.

PMID- 9602426
TI  - Characteristics of cardiac hypertrophy in the juvenile visceral steatosis mouse
      with systemic carnitine deficiency.
AB  - The juvenile visceral steatosis (JVS) mouse exhibits hereditary systemic
      carnitine deficiency and develops cardiac hypertrophy. The aim of this study was
      to clarify the characteristics of cardiac hypertrophy in the JVS mouse. Total
      carnitine content in IVS mouse heart was about 10% of that of control mouse heart
      at 4 and 8 weeks of age. The heart weight/body weight ratio was bigger in JVS
      mice than that in control mice at 2 weeks of age, and this difference in ratio
      increased with age. The wall areas of both ventricles and septum in JVS mice were
      larger than those of the control mice at 2 and 8 weeks. The myocyte diameter in
      both ventricular walls and septum in JVS mice was longer than that of the control
      mice. On electron microscopy, the percent of mitochondria in the myocyte was 66%
      in JVS mice, and 37% in control mice. The percent of lipid fraction in JVS mice
      was six-fold higher than that in control mice. Total content of adenine
      nucleotides in JVS mouse heart was about 60% of that in control mouse heart.
      Adenylate energy charge in JVS mouse heart was 63 and 45% of that in the control
      mouse heart at 4 and 8 weeks, respectively. Overall, the cardiac enlargement
      observed in this animal model could be accounted for by a proportional increase
      in the myocyte diameter in the ventricles and septum, accompanied by an increase
      in mitochondria. Furthermore, this cellular growth is associated with decreases
      in the levels of ATP and ADP, and adenylate energy charge.

PMID- 9602428
TI  - Time-dependent protection by Na+/H+ exchange inhibition in a regionally ischemic,
      reperfused porcine heart preparation with low residual blood flow.
AB  - Inhibition of Na+/H+ exchange has been shown to protect the ischemic reperfused
      myocardium. This study investigated the time-dependent beneficial effect of the
      Na+/H+ exchange inhibitor HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanedine
      methanesulphonite, cariporide). The left anterior descending coronary artery was
      ligated in 21 pigs (seven control animals) for 60 min and then reperfused for 24
      h. An extracorporeal bypass system was used to achieve a constant residual blood
      flow of 3 ml/min within the ischemic myocardium. Cariporide (1 mg/kg) was
      injected intravenously in seven pigs after 15 min of ischemia (group A), and in
      another seven animals after 45 min of ischemia (group B). Histochemical
      (tetrazolium stain) and histologic infarct sizes were determined at the end of
      the experiments. Regional systolic shortening was determined by sonomicrometry.
      Mean calculated residual blood flows (ml/min/g of ischemic myocardium) amounted
      to 0.106 (group A), 0.093 (group B), and 0.117 (control group). Histochemical
      (32.9 +/- 21%) and histologic infarct sizes (36.7 +/- 17.7%) were significantly
      reduced in group A compared to both the control group (histochemical infarct
      size, 62.5 +/- 16.1%, P < 0.01; histologic infarct size. 67.8 +/- 16.3%, P =
      0.013) and group B (histochemical infarct size 64.8 +/- 12.2%, P < 0.01;
      histologic infarct size 67.1 +/- 15.6%, P < 0.01). Infarct sizes of group B did
      not differ from control values. Recovery of regional systolic shortening after 24
      h of reperfusion was insignificantly improved in group A compared to both other
      groups. In conclusion, inhibition of Na+/H+ exchange during early ischemia
      reduced cell death in an ischemic reperfused preparation with low residual blood
      flow.

PMID- 9602429
TI  - Changes of creatine kinase gene expression in rat heart post-myocardial
      infarction.
AB  - Creatine kinase (CK) plays a crucial role in cardiac energy transduction. During
      chronic cardiac stress conditions leading to hypertrophy and/or heart failure,
      the profile of CK isoenzyme activities changes towards a fetal pattern with
      increases of BB- and MB-CK and decreases of MM-CK and mito-CK. Changes of
      myocardial CK gene expression are only indirectly reflected by measurements of CK
      activities. The purpose of this work was, therefore, to determine myocardial
      expression of B-, M- and sarcomeric mito-CK genes in an animal model of heart
      failure where hemodynamic alterations and CK system changes are well defined,
      that is, in the rat heart post-myocardial infarction. Intact residual left
      ventricular myocardium was harvested 2 months following infarction (MI; n = 7) or
      sham operation (sham; n = 6) after in vivo left-ventricular end-diastolic
      pressure (LVEDP) was recorded. Total CK activity was measured
      spectrophotometrically, CK isoenzyme distribution with agarose gel
      electrophoresis. Steady state mRNA levels coding for B-, M- and mito-CK genes
      were measured with quantitative PCR and were normalized for GAPDH expression.
      Total CK activity tended to be reduced in MI (5.51 +/- 0.62 IU/mg protein)
      compared to sham (6.77 +/- 0.24; P = 0.55). CK isoenzyme distribution showed an
      increase of fetal BB- + MB-CK (MI 22.0 +/- 3.1%, sham 15.1 +/- 1.0%; P < 0.05),
      no change of MM-CK and a decrease of mito-CK (27.0 +/- 1.5% sham, 20.8 +/- 2.0%
      MI: P < 0.05). Relative B-CK mRNA levels increased (sham 0.46 +/- 0.06, MI 1.03
      +/- 0.09; P < 0.05) and M-CK mRNA levels decreased (sham 1.06 +/- 0.08. MI 0.66
      +/- 0.09; P < 0.05) significantly post-MI. The increase of B-CK mRNA (r = 0.72; P
      = 0.009) and the decrease of M-CK mRNA (r = 0.76; P = 0.003) correlated
      significantly with in vivo LVEDP. Mito-CK mRNA levels remained unchanged after MI
      (sham 0.94 +/- 0.16, MI 0.98 +/- 0.09). Intact residual left-ventricular
      myocardium post-MI is characterized by increased B-CK-mRNA and reduced M-CK-mRNA
      expression.

PMID- 9602430
TI  - Differential expression of heat shock proteins in normal and failing human
      hearts.
AB  - BACKGROUND: Heat shock proteins (hsp) constitute an endogenous stress response
      that protects cells from injury. Most work on these important proteins has
      focused on the immediate response to acute stress in cell culture systems and
      mammalian models of heart disease. Little is known about the expression of the
      hsps in human hearts. We were interested in whether there was increased
      expression of the hsps in heart failure, a setting of chronic, sustained stress.
      Five different hsps were examined: hsp27, hsp60, hsp72, hsc70 and hsp90. METHODS
      AND RESULTS: Three groups of explanted hearts were studied: dilated
      cardiomyopathy (DCM), ischemic cardiomyopathy (IHD), and normal controls. Western
      blotting with a standard curve of purified protein on each blot was used to
      quantify the expression of the hsps. Hsp27 was increased almost two-fold in DCM
      compared to normal hearts, and was significantly greater than in IHD hearts.
      Levels of hsp60 were doubled in both DCM and IHD hearts (P < 0.05). Hsp72, hsc70
      and hsp90 were not significantly changed. CONCLUSIONS: This study shows for the
      first time that differential changes in hsp levels occur in end-stage heart
      failure. Since hsps can render cells resistant to apoptosis, and are associated
      with the mitochondria and the cytoskeleton, which are known to be abnormal in
      heart failure, these studies may lead to new insights into the pathogenesis of
      cardiac decompensation.

PMID- 9602431
TI  - Effects of L-glutamine on post-ischaemic cardiac function: protection and rescue.
AB  - We investigated the effects of L-glutamine (0-20 mM) on cardiac function. The
      isolated perfused working rat heart (left atrial and aortic pressures of 5 and 70
      cm H2O, respectively) was subjected to 20 min of normothermic low-flow ischaemia
      followed by reperfusion for 35 min. In the absence of glutamine, ischaemia
      reperfusion caused an immediate significant (P < 0.01) fall in cardiac output
      from 46 to 20 ml/min, with a further deterioration to 17 ml/min at 35 min
      reperfusion. Ischaemia also caused a significant (P < 0.05) fall in myocardial
      glutamate from 2.6 to 1.8 mumol/g wet weight; and ischaemia-reperfusion caused
      significant (each P < 0.05) diminutions of myocardial ATP from 3.5 to 1.0 mumol/g
      wet weight and phosphocreatine from 4.8 to 1.5 mumol/g wet weight and resulted in
      significant (P < 0.05) accumulation of myocardial lactate from 0.9 to 4.3 mumol/g
      wet weight. Glutamine, present throughout the perfusion protocol (i.e. prior to
      ischaemia), at or above 1.25 mM, prevented the post-ischaemic diminution of
      cardiac output and the deleterious changes in myocardial metabolites. Post
      ischaemic treatment with glutamine at 2.5 mM completely prevented the post
      ischaemic diminution of cardiac output and restored the myocardial metabolites to
      normal. CONCLUSIONS: Glutamine may be suitable as a cardioprotective and rescue
      agent. These effects may be mediated by maintenance of myocardial glutamate, ATP
      and phosphocreatine: and prevention of lactate accumulation.

PMID- 9602432
TI  - Protection against myocardial ischemic/reperfusion injury by inhibitors of two
      separate pathways of Na+ entry.
AB  - Previous work has demonstrated that drugs which inhibit Na+ entry through voltage
      sensitive Na+ channels, or via Na(+)-H+ exchange protect the heart from ischemic
      reperfusion damage. The purpose of our study was to determine whether these drugs
      in combination will have an additive protective effect in Langendorff-perfused
      hearts. During reperfusion following 30 min of ischemia, developed tension and
      resting tension were 24 +/- 3 and 162 +/- 5%, respectively, of pre-ischemic
      values in non-treated ischemic hearts. The administration of HOE-642 to inhibit
      Na+/H+ exchange increased active developed tension (DT) to 58 +/- 2% of pre
      ischemic levels and decreased resting tension (RT) to 111 +/- 3% of pre-ischemic
      levels. The administration of tetrodotoxin (TTX) to block the Na+ channel
      increased DT to 56 +/- 3% of the pre-ischemic level and reduced the RT to 126 +/-
      12% of the pre-ischemic level. Together, HOE-642 and TTX increased recovery of DT
      to 63 +/- 2% of pre-ischemic levels and improved RT to 116 +/- 4% of pre-ischemic
      levels after 30 min of reperfusion. All drug treatment protocols significantly
      lowered the creatine phosphokinase activity measured in the coronary effluent in
      comparison to that observed in the non-treated hearts. These data demonstrate
      that inhibition of Na+ entry through either Na(+)-H+ exchange or the Na+ channel
      protects the heart from ischemic injury, but there is no additional benefit of
      blocking both routes of Na+ entry simultaneously. This suggests that a threshold
      level of Na+i may be a critical factor in ischemic cardioprotection.

PMID- 9602433
TI  - Manganese reduces myocardial reperfusion injury on isolated rat heart.
AB  - It has been shown that reactive oxygen species produced during the early phase of
      myocardial post-ischemic reperfusion are one of the main causes of reperfusion
      injury. This observation has led to various antioxidant strategies using many
      reactive oxygen species scavengers, including manganese complexes. The aim of the
      present work was to provide a reference study of the effects of manganese itself
      (MnCl2) on isolated rat hearts submitted to global total normothermic ischemia
      (30 min) and reperfusion (60 min). McCl2 was administered either during the first
      10 min reperfusion (10(-5)M and 10(-4)M) or throughout reperfusion (10(-4)M).
      After 10 min reperfusion, no functional difference was evidenced between control
      and manganese-treated groups, whereas high energy phosphate contents were
      significantly higher in treated groups. MnCl2 10(-4)M enhanced the recovery of
      developed pressure between 40 and 55 min reperfusion. At the end of reperfusion,
      hearts treated during the first 10 min reperfusion showed a better metabolic
      recovery. The group treated throughout reperfusion showed a better metabolic
      recovery, but a reduced coronary flow and a weak recovery of developed pressure.
      These results suggest that MnCl2, administered during the early phase of
      reperfusion, protects against myocardial reperfusion injury. This effect might be
      mediated by manganese antioxidant properties.

PMID- 9602434
TI  - Cardiotrophin-1 induces heat shock protein accumulation in cultured cardiac cells
      and protects them from stressful stimuli.
AB  - Cardiotrophin-1 (CT-1) was originally identified as a molecule capable of
      inducing cardiac hypertrophy. We show here that treatment of cultured neonatal
      cardiocytes with CT-1 induces enhanced synthesis of the heat shock proteins hsp70
      and hsp90, with hsp70 levels being enhanced three-fold and hsp90 levels being
      enhanced seven-fold. Such CT-1-treated cells are protected against subsequent
      exposure to severe thermal or ischaemic stress, as assayed both by measures of
      total cell death, such as trypan blue exclusion and LDH release, and by measures
      of apoptosis, such as propidium-iodide-staining and TUNEL-labelling. Hence, CT-1
      can induce the protective hsps and protect cardiac cells from diverse stresses.

PMID- 9602435
TI  - Tolerance to ischaemia and ischaemic preconditioning in neonatal rat heart.
AB  - Although there is much information on ischaemic preconditioning in the adult
      myocardium, this phenomenon has not yet been investigated in neonatal hearts. To
      examine the early development of cardiac tolerance to ischaemia and the possible
      protective effects of preconditioning, rat hearts isolated on days 1, 4 and 7 of
      postnatal life were perfused (Langendorff) with Krebs-Henseleit solution at
      constant pressure, temperature (37 degrees C) and rate (200 beats/min). Developed
      force (DF) of contraction was measured by an isometric force transducer, and
      analysed using an on-line computer. Hearts were exposed to 40 or 60 min of global
      ischaemia followed by 30 min of reperfusion. Preconditioning was induced by three
      3-min periods of global ischaemia, each separated by 5-min periods of
      reperfusion. Developmental changes in expression of protein kinase C (PKC)
      isoforms, and their activation following preconditioning, were estimated using
      Western blot analysis. Recovery of contractile function during reperfusion
      decreased from day 1 (48 +/- 2%) to day 4 (42 +/- 1%) and day 7 (33 +/- 2%).
      Preconditioning failed to improve ischaemic tolerance on day 1 (46 +/- 2%) and on
      day 4 (43 +/- 3%), but pronounced effect was observed on day 7 (40 +/- 2%).
      Prolonging the period of sustained ischaemia from 40 to 60 min on day 1 did not
      lead to a better recovery of contractile function in preconditioned hearts. PKC
      isoforms alpha, delta, epsilon and zeta were expressed in the ventricular
      myocardium during the first week of life, but there was no evidence of
      translocation following preconditioning on day 7. It may be assumed that the
      decreasing tolerance of the heart to ischaemia during early postnatal life is
      counteracted by the development of an endogenous protection.

PMID- 9602436
TI  - Intramyocardial infusion of FGF-1 mimics ischemic preconditioning in pig
      myocardium.
AB  - Previous studies on the mRNA and protein level suggested a cardioprotective role
      of FGF-1. These presumed actions of FGF-1 and FGF-2, as well as the underlying
      mechanisms, were investigated in this study. Human recombinant FGF-1 (0.5
      microgram/ml, 20 microliters/min) and FGF-2 (2 micrograms/ml) were applied by
      means of direct intramyocardial infusion (IM) for 60 min prior to a 60 min LAD
      occlusion and 120 min reperfusion. Myocardial infarction compared to the region
      at risk was significantly decreased by FGF-1 and FGF-2 treatment (FGF-1: 51.8 +/-
      7.7%, respectively. FGF-2: 57.3 +/- 6.5% v control 83.4 +/- 2.8%, P < 0.05). The
      increase in survival time was about 33 min, and equalled that of ischemic
      preconditioning. This effect was caused by the mitogenic part of the molecule,
      since infusion of a truncated version of FGF-1 (0.5-1 microgram/ml), lacking
      mitogenicity but maintaining hemodynamic activity, did not induce
      cardioprotection (78.3 +/- 0.73% v control 83.4 +/- 2.8%). Suramin (0.5
      microgram/ml) prevented the observed cardioprotection (77.0 +/- 1.2% v control
      83.4 +/- 2.8%) proving that the cardioprotective effect is receptor-mediated.
      Genistein (0.5 microgram/ml), an inhibitor of tyrosine kinases, abolished the
      cardioprotection as well (77.2 +/- 2.4% v control: 83.4 +/- 2.8%).
      Immunohistochemical staining revealed an uptake and translocation of exogenous
      FGF-1 to a (peri-)nuclear localization in myocytes and into non-myocytes for FGF
      2. We conclude that both FGF-1 and FGF-2 are cardioprotective (FGF-1 being more
      active on a molar basis), and mimic ischemic preconditioning. Their actions are
      receptor-mediated and receptor activation is involved. Uptake and transport to a
      (peri-)nuclear localization, seems to be a pathway of minor relevance, since it
      could not be blocked by tyrosine kinase receptor inhibition. Tyrosine kinase
      coupled receptor occupation in general is not protective as demonstrated by the
      lack of effect with VEGF-infusion.

PMID- 9602437
TI  - Ribose-enhanced synthesis of UTP, CTP, and GTP from parent nucleosides in cardiac
      myocytes.
AB  - The participation of ribose and its metabolites in some nucleoside salvage
      reactions is well established. Isolated adult rat cardiac myocytes were used as a
      model system to determine whether ribose acts as a general stimulant of salvage
      reactions in cardiac muscle, or whether only certain classes of nucleosides are
      affected by ribose. Myocytes were incubated with [3H]-adenosine, [3H]-cytidine,
      [3H]-guanosine, [3H]-thymidine, or [3H]-uridine for 30 or 60 min in the presence
      or absence of 5 mM ribose. The cells were extracted and the extracts assayed for
      [3H]-nucleoside and [3H]-nucleotide products. Salvage synthesis of cytosine,
      guanine and uracil nucleotides from the parent nucleosides was stimulated by
      ribose. Guanosine and uridine salvage appeared saturated at 50 microM external
      nucleoside (the dose response of cytidine salvage was not examined). Adenosine
      salvage was unaffected by ribose addition; the response to increasing external
      adenosine concentration was non-Michaelis-Menten, showing a peak of activity at
      25 microM external nucleoside. Thymidine salvage was also unaffected by ribose,
      and was saturated at 50 microM external thymidine. These data suggest that
      adenosine and thymidine are metabolized to their respective nucleotide
      monophosphates by kinase activity. Cytidine, guanosine, and uridine salvage are
      stimulated by ribose, and must therefore be metabolized in part by nucleoside
      phosphorylase and phosphoribosyltransferase activity.

PMID- 9602438
TI  - Interleukin-10 inhibits human vascular smooth muscle proliferation.
AB  - Arterial injury results in the elaboration of pro-inflammatory substances
      including cytokines and peptide growth factors which act to modify vascular
      smooth muscle (VSMC) proliferation and migration with resultant vessel stenosis.
      Produced by T-lymphocytes and macrophages, interleukin-10 (IL-10) is an anti
      inflammatory cytokine in several cell lines. We hypothesized that IL-10 may
      participate in vascular remodeling by inhibiting VSMC proliferation. Human aortic
      VSMCs were isolated and cultured. Proliferation assays were performed to
      determine the effect of the effect of IL-10 on (1) unstimulated, (2) cytokine
      (tumor necrosis factor-alpha: TNF alpha)-stimulated, and (3) growth factor (basic
      fibroblast growth factor: bFGF)-stimulated VSMC proliferation. Compared to
      control, both TNF alpha and bFGF-stimulated VSMC proliferation (P < 0.002). IL-10
      alone had no effect on cell growth. However, with TNF alpha or bFGF-stimulation,
      physiologic doses of IL-10 inhibited both VSMC DNA synthesis and VSMC growth (P <
      0.001). Furthermore, IL-10 was effective in inhibiting TNF alpha-induced
      proliferation at a dose as low as 10 fg/ml (P < 0.001) and bFGF-induced
      proliferation at a dose as low as 1 pg/ml (P < 0.001). In conclusion, TNF alpha
      and bFGF stimulate human VSMC growth. IL-10 potently abrogates the proliferative
      response to these atherogenic mitogens. IL-10 might represent an endogenous
      source of immune-mediated atherprotection and when given exogenously, may prove
      to be a novel therapeutic agent in regulating vessel wall remodeling following
      vascular injury.

PMID- 9602439
TI  - Public health and the private finance initiative.

PMID- 9602440
TI  - Health care systems in transition. II: East Asia--the roaring tigers.

PMID- 9602441
TI  - Health care systems in transition. II. Taiwan, Part I. A general overview of the
      health care system in Taiwan.

PMID- 9602442
TI  - Health care systems in transition. II. Taiwan, Part II. The current status of HIV
      AIDS in Taiwan.

PMID- 9602443
TI  - Health care systems in transition. II. Singapore, Part I. An overview of health
      care systems in Singapore.

PMID- 9602444
TI  - Health care systems in transition. II. Singapore, Part II. The current status of
      HIV-AIDS.

PMID- 9602445
TI  - Health care systems in transition. II. Japan, Part I. An overview of the Japanese
      health care systems.

PMID- 9602446
TI  - Health care systems in transition. II. Japan, Part II. The current status of AIDS
      HIV in Japan.

PMID- 9602447
TI  - Health care systems in transition. II. Korea, Part I. An overview of health care
      systems in Korea.

PMID- 9602448
TI  - Health care systems in transition. II. Korea, Part II. The current status of HIV
      AIDS in Korea.

PMID- 9602449
TI  - For debate. Local health and lifestyle surveys--do the results justify the costs?

PMID- 9602450
TI  - Population screening in the NHS: a systematic pathway from evidence to policy
      formulation.
AB  - In 1994 the Chief Medical Officer of England set out a framework for the
      evaluation and implementation of national screening programmes in the National
      Health Services (NHS). The framework highlighted the importance of the link
      between research evidence and the formulation of national policy. It also
      stressed the necessity for monitoring, evaluation and quality control as integral
      components for all new screening programmes. There is now an established link
      between the Health Technology Assessment programme of the NHS Research and
      Development Directorate and the NHS's new policy advisory group, the National
      Screening Committee. The objective of this systematic approach is to ensure that
      screening programmes are not introduced into the NHS unless there is robust
      evidence that benefit outweighs harm. The Population Screening Panel, an advisory
      panel of the NHS Health Technology Assessment programme, has the responsibility
      for determining priorities in research on proposed or existing population
      screening programmes. The National Screening Committee has a remit to consider
      this research evidence and to advise government ministers and the NHS on the
      appropriateness of the implementation, development and modification of national
      screening programmes. The example of prostatic cancer screening is presented as
      an illustration of how the NHS is developing a systematic approach to the
      implementation of screening policy based upon the strategic commissioning of
      research evidence.

PMID- 9602451
TI  - Assessment of the reproducibility of clinical coding in routinely collected
      hospital activity data: a study in two hospitals.
AB  - BACKGROUND: The aim of the study was to assess the reproducibility of clinical
      coding in two National Health Service hospitals within North West Thames region.
      METHODS: A retrospective audit was carried out, of clinical coding in hospital
      episode statistics, involving comparison of the codes assigned by local staff
      with those assigned by members of an external team unaware of the locally
      assigned codes. Where local and external coders disagreed, the records were
      reviewed for a third time by a further independent coder. The subjects were a
      random sample of 1607 non-maternity, non-psychiatric admissions occurring between
      1991 and 1993, stratified for year and type of disease (asthma, diabetes,
      appendicitis, fractured femur and 'general'--a random selection of any
      diagnoses). The main outcome measures were the levels of exact agreement between
      local and external teams over codes for main diagnosis and procedure, and the
      level of approximate agreement (over the first three characters of the ICD-9 code
      for diagnosis and the letter and first two digits of the OPCS-4 code for
      procedure). For disagreements, the outcome measure was the level of agreement
      between the 'third' coder and the local and external coders. RESULTS: For the
      main diagnosis in the 'general' group at hospital A, internal and external coders
      agreed exactly in 43 per cent of the admissions examined and agreed
      'approximately' in 55 per cent (kappa = 0.54). For hospital B the corresponding
      figures were 60 per cent and 72 per cent (kappa = 0.72). Approximate agreement
      was higher for the specific diseases considered, particularly for asthma (A: 86
      per cent; B: 91 per cent) and fractured femur (A: 84 per cent; B: 89 per cent).
      For the main procedure at hospital A, there was exact agreement for 58 per cent
      and approximate agreement for 70 per cent (kappa = 0.66). For hospital B, the
      corresponding figures were 76 per cent and 83 per cent (kappa = 0.80). In cases
      of disagreement over the first three digits of the ICD-9 code for main diagnosis,
      the third coder disagreed with both local and external coders in 53 per cent at
      hospital A and 38 per cent at hospital B. Agreement was slightly better for
      discharges in 1992-1993 than in 1991-1992. CONCLUSIONS: The full clinical codes
      in NHS hospital episode statistics (HES) data should be treated with caution. The
      first three characters of ICD-9 codes for diagnoses and the OPCS-4 codes for
      procedures were more reliable. For some specific conditions such as asthma and
      fractured femur, reliability of the first three characters is much higher (for
      example, 86 per cent and 91 per cent for asthma in the two hospitals), but for
      the full codes can be worse. Secondary diagnoses or comorbidities may be
      significantly undercoded. A higher level of agreement in 1992-1993 than in 1991
      1992 suggests that coding may be improving.

PMID- 9602452
TI  - Cycle helmet ownership and wearing; results of a survey in South Staffordshire.
AB  - BACKGROUND: Despite increasing evidence indicating that wearing cycle helmets can
      reduce the severity of head injuries, particularly in children, there is a
      paucity of local data on cycle helmet ownership and wearing rates. These data
      together with an understanding of the factors which influence these rates are
      important in developing appropriate health promotion programmes. METHOD: The
      objectives were to (1) establish patterns of cycle helmet ownership and wearing
      rates, and (2) determine factors influencing these rates. A descriptive survey
      involving a self-completed questionnaire was undertaken and a series of focus
      groups were also established. The setting was two high schools and four primary
      schools in each of the six boroughs or district councils within South
      Staffordshire involving 932 Year 6 and 2005 Year 10 children. RESULTS: The
      response ratio was 70.9 per cent from Year 6 and 80.9 per cent from Year 10,
      giving an overall response rate of 77.8 per cent. Most children (86.6 per cent)
      rode a bicycle and of these 42.8 per cent owned a cycle helmet. Just over a third
      (36.8 per cent) of Year 6 cyclists wore a helmet always or nearly always,
      compared with 13.7 per cent of Year 10 cyclists. Although the protective effect
      of cycle helmets was appreciated, many children did not see themselves as being
      personally at risk, particularly on short journeys. The appearance and comfort of
      the helmet appeared to be stronger factors influencing the uptake of helmets
      compared with cost. Both year groups were similarly concerned with comfort, but
      Year 10 children appeared more concerned with appearance than Year 6 children.
      CONCLUSIONS: Cycle helmet ownership and wearing is still disappointingly low,
      especially amongst older children. The factors influencing patterns of ownership
      and wearing are numerous and the interrelationships between them are complex,
      requiring a co-ordinated approach from a range of agencies. Cycle helmet
      legislation should be considered by the Government.

PMID- 9602453
TI  - The heart of darkness--does public health medicine offer any solutions for the
      next millennium in Africa?

PMID- 9602454
TI  - Influencing national policy; public health medicine and coronary heart disease
      prevention by general practitioners.
AB  - BACKGROUND: Public health medicine has a potentially important role to play in
      influencing national health policy. This study examines the role of public health
      medicine in the development of the policy on coronary heart disease prevention in
      general practice, exemplified by the 1990 and 1993 general practitioner (GP)
      contracts. METHODS: The methods of the study were qualitative. There were two
      sources of data: interviews with 33 key informants and analysis of documents
      relating to the policy process. RESULTS: Public health medicine as an organized
      medical specialty had little involvement with the development of the policy. The
      reasons for this include a closed policy process which tended to exclude those
      not from a primary care background, the role of political factors, the
      predominance of secondary care concerns by public health medicine in the early
      1990s, and differences in perspective between primary care and public health
      medicine. Public health medicine structures did not have systematic links with
      the policy process. Public health physicians working in research had more
      influence, but this was also limited by the absence of any systematic scientific
      advisory links. CONCLUSIONS: To influence national policy it is necessary to have
      formal and informal systematic links with the policy-making machinery at all
      levels of the specialty.

PMID- 9602455
TI  - Views of doctors in the United Kingdom about their own professional position and
      the National Health Service reforms.
AB  - BACKGROUND: In the course of national studies of doctors' career choices and
      progression, we received spontaneous comments from respondents about job
      satisfaction and the National Health Service reforms. To assess whether such
      comments were representative, or whether they reflected minority views, we added
      questions to subsequent questionnaires to gauge systematically how doctors view
      their own professional position and the wider NHS. METHOD: Self-administered
      questionnaire were sent to all 10,504 qualifiers of 1977, 1988 and 1993 from UK
      medical schools. RESULTS: A total of 7391 responded (70 per cent). Most doctors
      in UK medicine were positive about the career opportunities they have had (66 per
      cent of relevant respondents), their future prospects (68 per cent) and their
      present position (80 per cent). Few were positive about the NHS reforms (9 per
      cent) and the effects of the reforms on their own professional work (9 per cent).
      Only 0.2 per cent of the 1993 qualifiers scored their impression of the internal
      market as 'strongly favourable'. CONCLUSIONS: In recent years the NHS shifted
      from a collaborative to a competitive model of management of health care with the
      establishment of an internal market. The great majority of respondents viewed
      recent changes and the internal market unfavourably. This is not, however, a
      reflection of more widespread discontent with their work. The majority viewed
      their own professional opportunities and present position favourably.

PMID- 9602456
TI  - Public health debacle in South Asia: a reflection of the crisis in welfarism.
      South Asian regional meeting on health effects of structural adjustment policies,
      New Delhi, September 1997.

PMID- 9602457
TI  - Emergency admissions of older people to hospital: a link with material
      deprivation.
AB  - BACKGROUND: The aim was to investigate whether variations in emergency admission
      to hospital amongst older people in Leicestershire vary with the level of
      material deprivation of the area in which they live. METHODS: Data were extracted
      from the Trent Patient Information System for patients aged 65 and over, admitted
      as an emergency medical admission to Leicestershire's acute and community
      hospitals on at least one occasion during the period October 1993-September 1994.
      The 1991 Census was used to examine the nature of the areas from which these
      emergency admissions were drawn and variations in emergency admission rates
      across Leicestershire. The relationship between emergency medical admissions and
      age, sex and material deprivation as measured by the Townsend deprivation score
      was examined. RESULTS: There were 13,305 people aged 65 or over with at least one
      emergency medical admission out of an estimated population (65 and over) in 1994
      of 134,608 (9.9 per cent). Unconditional logistic regression showed that the risk
      of emergency admission increased with age and was also higher for men than for
      women. Emergency admissions increased significantly with increasing deprivation
      for each age group. This was most notable in the 65-74 years age group, yielding
      an odds ratio of 2.06 [95 per cent confidence interval (1.86, 2.29)], when
      comparing those from the most deprived areas with those from the least deprived
      areas. CONCLUSIONS: The increased risk of emergency medical admission to
      hospital, which is associated with residence in areas characterized as deprived
      by Census-based indicators, suggests there are enduring inequalities in health or
      health care amongst older people. Inequalities noted for all ages persist into
      old age, although in the 'oldest' age groups, the effect is weaker. Material
      deprivation may also be a proxy for other factors, such as differences in social
      support and the type of care received.

PMID- 9602458
TI  - Does the Child Health Computing System adequately identify children with cerebral
      palsy?
AB  - BACKGROUND: This paper assesses the usefulness of the Child Health Computing
      System as a source of information about children with cerebral palsy. METHODS: A
      comparative survey of information held on the Child Health Computing System
      (CHCS) and the Northern Ireland Cerebral Palsy Register (NICPR) in one Health and
      Social Services Board in Northern Ireland was carried out. The sample comprised
      children with cerebral palsy aged 5-9 years. RESULTS: Of the 135 cases recorded
      on the NICPR, 47 per cent were not found on the CHCS; the majority of these
      children had no computer record of any medical diagnosis. Of the 82 cases
      recorded on the CHCS, 10 (12 per cent) were not found on the NICPR; five of these
      cases (6 per cent) were found on follow-up not to have CP. CONCLUSIONS: Unless
      improvements are made in case ascertainment, case validation and recording
      activities, the evidence suggests that the CHCS will not be able to provide the
      same quality of information for needs assessment and surveillance of very low
      birthweight infants in relation to cerebral palsy as is provided by a specialist
      case register.

PMID- 9602460
TI  - Journals, BUMPH and all such things: famine amidst plenty.

PMID- 9602459
TI  - Quarterly Communicable Disease Review July to September 1997. From the PHLS
      Communicable Disease Surveillance Center.

PMID- 9602461
TI  - Research and the Internet.

PMID- 9602462
TI  - A case of invasive serogroup C meningococcal disease after a community
      vaccination programme in Rotherham, South Yorkshire.

PMID- 9602463
TI  - Sex and blood-brain barrier.

PMID- 9602464
TI  - Purinoceptor-mediated modulation of purine and neurotransmitter release from
      nervous tissue.
AB  - The purpose of this review is to analyse critically our present knowledge on
      purine release, and in particular the role of these substances as modulators of
      the nervous transmission. Multiple purine receptor subtypes have been identified,
      cloned and functionally characterised. Neurons and glial cells are considered to
      be important sources of extracellular adenine-based purines. The released
      nucleotides and nucleosides, by interacting with their specific neuronal and
      glial receptors, activate a complex autocrine and/or paracrine system for the
      modulation of the release either of neurotransmitters or the purine ones. Guanine
      based purines which are released from astrocytes co-operate with adenine-based
      compounds in this modulation.

PMID- 9602465
TI  - The effect of chronic benzodiazepines exposure on body weight in rats.
AB  - Changes in body weight (BW) in female rats treated for 5 weeks (wk) with weekly
      subcutaneous implantation of silastic capsules containing different
      benzodiazepines (BZs): diazepam (DZ) 90, 180, 360 and 540 mg wk-1; nordiazepam
      (ND) 600 mg wk-1; oxazepam (OX) 600 mg wk-1 and flunitrazepam (FN) 540 mg wk-1
      and in male rats exposed to DZ (540 mg wk-1) were evaluated herein. Rats (female
      and male) implanted with empty capsules served as controls. The BW gain was
      significantly higher in male than in female rats (both DZ-treated and controls).
      The BW gain increased with increasing doses of DZ but slowed with time of
      exposure. In comparison to control rats, the BW gain was significantly higher in
      DZ-(540 mg wk-1) and OX- but not in ND- and FN-treated female rats. However, the
      differences between BZs were not of statistical significance. In rats exposed to
      empty capsules (male, female); DZ (male); ND and OX (female) the BW gain
      increased with time (1-4 wk) while in rats exposed to DZ and FN (female) the BW
      stabilised within 2 wk. Acute injection of the central BZ receptor antagonist,
      flumazenil (40 mg kg-1, i.v., 5th wk of chronic exposure), tended to inhibit the
      time-related BW gain in rats exposed to empty capsules (male, female), DZ (male),
      ND and OX (female) but did not affect the BW in DZ- (540 mg wk-1) and FN-exposed
      rats (female) where BW stabilised prior to FLU injection. Repeated administration
      of flumazenil (30 mg kg-1 wk-1, i.p.) did not affect the BW gain in DZ- and ND
      treated female rats. The present data indicate that different BZs have different
      effects on BW gain in the rat suggesting that different subtypes of BZ receptors
      are involved.

PMID- 9602466
TI  - Effect of triterpenes from Crataeva nurvala stem bark on lipid peroxidation in
      adjuvant induced arthritis in rats.
AB  - Lupeol, a pentacyclic triterpene was isolated from C. nurvala stem bark and its
      ester lupeol linoleate was synthesised. These triterpenes were tested for their
      anti-inflammatory activity in complete Freund's adjuvant induced arthritis rats.
      For some time free radicals have been implicated in damage to connective tissues
      during inflammatory conditions and arthritis. Lupeol and lupeol linoleate were
      administered orally at the dose level of 50 mg kg-1 body weight daily for 8 days,
      from the 11th to 18th day postadjuvantly. There was a significant increase in
      lipid peroxide level in plasma of arthritic rats but it was found to be decreased
      in the liver. The antioxidant enzymes superoxide dismutase, glutathione
      peroxidase and catalase were elevated in both the liver and haemolysate in
      adjuvant-induced rats. Blood glutathione was decreased in arthritis. The
      triterpenes reduced the above alterations produced in arthritic animals. The
      effect of lupeol linoleate was found to be better in this respect when compared
      with lupeol.

PMID- 9602467
TI  - In vitro interaction between spiramycin and polymorphonuclear neutrophils
      oxidative metabolism.
AB  - PMNs are a major component of body defense against microbial invasion, involving
      reactive oxygen species in great quantity, which could benefit from antibiotic
      therapy. Recently, possible antibiotic effects on phagocyte functions (impairment
      or stimulation of reactive oxygen species production) were studied. In our study,
      an in vitro evaluation was made on macrolide activity on phagocyte respiratory
      burst functions, using assay of superoxide anion (O2.-) in response to four
      stimuli systems: N-formyl Met-Leu-Phe (fMLP), an analogue of bacterial
      chemotactic factors; 4 beta-phorbol 12-myristate 13-acetate (PMA), a direct
      activator of protein kinase C (PKC); calcium ionophore (A23187), which acts
      directly on calcium influx; and a bacterial strain, Staphylococcus aureus. We
      have shown that spiramycin, at therapeutic plasma concentrations, increased O2.-
      generation by bacteria and fMLP-stimulated PMNs, with rate of 26% for 1 microgram
      ml-1 and 34% for 5 micrograms ml-1, respectively. This pro-oxidant effect,
      however, weaker, was observed when PMNs were stimulated by PMA. A weak anti
      oxidant effect was observed with A23187. For higher concentrations, spiramycin
      decreased strongly O2.- production, with IC50 values of 74 micrograms ml-1, 154
      micrograms ml-1, 296 micrograms ml-1 and 400 micrograms ml-1 when PMNs were
      stimulated with bacteria, A23187, fMLP and PMA, respectively. The effect of
      spiramycin seemed to result from an intracellular mechanism by intervention of
      PMN oxidative metabolism (NADPH-oxidase activation), rather than a simple
      chemical interaction, because no effect has been observed in acellular models.
      For higher spiramycin concentrations, the decrease of O2.- production observed
      could not be taken into consideration because this concentration was not used in
      therapy. The enhanced of O2.- production observed could be used in therapy, so as
      to increase PMNs bactericidal activity.

PMID- 9602468
TI  - S-adenosyl-L-methionine: role in phosphatidylcholine synthesis and in vitro
      effects on the ethanol-induced alterations of lipid metabolism.
AB  - Hepatic lipid metabolism is extremely modified by excessive ethanol consumption,
      but the cellular mechanisms of such alterations are still largely unexplored. S
      Adenosyl-L-methionine (SAMe) is known as an important methylating agent and as a
      precursor of glutathione and it has been shown to prevent some of the toxic
      effects of ethanol in the liver. We therefore studied the effects of ethanol on
      cholesterol synthesis in a human hepatomal cell line (HepG2), the kinetics of
      SAMe, and its putative protective effects on the alterations of lipid metabolism
      induced by toxic concentrations of alcohol. Incubation of HepG2 cells with
      [3H]SAMe resulted in a progressive increase in the labelling of
      phosphatidylcholine and of its two intermediates during synthesis starting from
      phosphatidylethanolamine. This process is enzymatic, since it does not take place
      in heat-inactivated cells. Also, ethanol induced an increase in cholesterol and
      triglycerides syntheses and a decrease in phospholipid labelling. These
      alterations were not prevented by SAMe 10(-4) M, indicating that the protective
      effects of the drug are related to other mechanisms of action such as reduced
      formation of collagen, restoration of glutathione levels, and normalization of
      membrane functions.

PMID- 9602469
TI  - Changes of blood pressure and aortic strip contractile responses to ET-1 of
      heterozygous female transgenic rats, TGR(mRen2)27.
AB  - We studied the contractile responses to endothelin-1 (ET-1) of aortic strips from
      female transgenic rats, TGR(mRen2)27, heterozygous for the Ren-2 mouse gene,
      during the phases of developing (blood pressure in rats aged 5 weeks; 156 +/- 8
      mmHg), steady (blood pressure in rats aged 11 weeks: 206 +/- 27 mmHg), and
      reversed (blood pressure in rats aged 35 weeks: 151 +/- 17 mmHg) hypertension.
      These responses were compared with those of aortae from sex- and age-matched,
      genetically homogeneous, normotensive Sprague-Dawley (SD) rats. Aortic strips
      from both transgenic and SD rats were deprived of endothelium before
      isometrically recording developed tension to cumulatively added ET-1. Aortic
      strips from 5- and 11-week-old female transgenic TGR(mRen2)27 (hfTG) rats
      responded to ET-1 with higher Emax values and lower EC50 values than those of age
      matched SD rats. Conversely, aortic strips from 35-week-old hfTG rats exhibited
      lower Emax and higher EC50 values than aortic strips from SD rats. Within the
      hfTG rats, aortic strips from 11-week-old rats showed increased Emax and
      decreased EC50 of ET-1 as compared with either 5- or 35-week-old hfTG rats. These
      data are in keeping with the hypothesis that ET-1 contributes to the hypertension
      of hfTG rats and suggest that an altered vascular responsiveness to the peptide
      may be implicated in the changes of their systolic blood pressure occurring with
      ageing in this animal model.

PMID- 9602470
TI  - Within-patient variability of hormone and cytokine concentrations in heart
      failure.
AB  - Several studies on disease and treatment effects on neurohormones have been
      conducted with small numbers of patients, using one blood sample as
      representative of their states. The aim of this study was to assess the within
      patient variability of plasma concentrations of several hormones and cytokines of
      recent interest, in patients with moderate heart failure and controlled stable
      background therapy over 3 weeks. Blood for neurohormone and cytokine assays was
      sampled in duplicate from 18 patients with moderate heart failure. After an
      initial visit, the patients were kept on stable therapy until the second blood
      sampling 21 +/- 3 days later. The plasma concentrations of several neurohormones
      (endothelin, renin, angiotensin II, aldosterone, norepinephrine) and cytokines
      (interleukin-6 (IL-6), interleukin-13 (IL-13), ciliary neurotrophic factor
      (CNTF), leukemia inhibitory factor (LIF) and soluble receptor type I of tumour
      necrosis factor-alpha, (sTNF-RI) were measured with immunochemical methods. Some
      cytokines (IL-13, CNTF and LIF) were not detected. Despite clinically
      satisfactory ACE inhibition, circulating angiotensin II and aldosterone levels
      were still elevated in some patients, suggesting aldosterone escape. The between
      visit agreement of plasma concentrations measured in duplicate was less than 35%
      for all circulating factors, except renin which showed a higher variability
      throughout the 3-week study period.

PMID- 9602471
TI  - Comparison of nitric oxide production by monocyte/macrophages in healthy subjects
      and patients with active pulmonary tuberculosis.
AB  - The aim of the present study was to determine the NO production by human cultured
      macrophages (m phi) and to compare the NO production between healthy subjects and
      patients with active pulmonary tuberculosis. The bioassay method was used for
      assessment of validation. Lipopolysaccharide (125 ng ml-1)-activated m phi from
      healthy and diseased subjects released a substantial amount of NO. NO synthase
      inhibitor, NG-nitro-L-arginine methyl ester, (0.1 mmol l-1) suppressed NO
      synthesis significantly in m phi of healthy subjects. Nitrite formation measured
      by the diazotization method in the supernatants taken from cultured m phi of
      tuberculous patients were significantly lower than the healthy subjects. The
      supernatants obtained in both subjects caused relaxation of guinea-pig aorta
      reversed by methylene blue (10 mumol l-1). There was a significant difference
      between relaxations of healthy and diseased supernatants. Nitrite formation
      measured by the bioassay method in the supernatants taken from cultured m phi of
      tuberculous patients was significantly higher than the healthy subjects. It was
      concluded that NO production appeared to be decreased in tuberculosis. The reason
      for decreased production of NO in tuberculosis may be related to the interaction
      of several cytokines and/or eicosanoids by means of the disease related induction
      of immune reactions.

PMID- 9602472
TI  - Effect of additional testosterone on purinergic responses in isolated rabbit
      corpus cavernosum strips.
AB  - Recently, it has been demonstrated that the endothelium of corpus cavernosum (CC)
      plays an important role on smooth muscle relaxation, which is crucial to initiate
      and maintain erection. We investigated the effect of long-lasting additional
      testosterone propionate (TP) therapy on endothelium-dependent and -independent
      relaxations of isolated rabbit CC. Isolated CC strips were mounted in organ baths
      and isometric tension was recorded. Addition of a specific inhibitor of nitric
      oxide synthesis, NG-nitro-L-arginin methyl ester (L-NAME), into the organ bath
      had no effect on the relaxation responses to adenosine (ADO), adenosine 5'
      triphosphate (ATP) and sodium nitroprusside (SNP) in isolated CC strips
      precontracted with phenylepherine, but completely inhibited relaxation responses
      produced by ADP. Adenosine and adenine nucleotides relaxed the phenylepherine
      induced contractile response in control strips with the potency order: ADO (62.8
      +/- 3.2%) > ATP (37.1 +/- 5.2%) > ADP (25.8 +/- 2.5%). The relaxation responses
      to ADO, ATP and SNP in isolated rabbit CC strips were not significantly altered
      by additional TP therapy. The relaxation responses produced by ADP were
      significantly enhanced following 1 and 2 months TP therapy as compared with
      controls. However, in the group treated with TP for 2 months followed by a 2
      months drug-free period, relaxation responses were significantly reduced compared
      to 1 and 2 months treatment groups, and approached control values. Increased
      relaxation responses to ADP following 1 and 2 months additional TP therapy may be
      a result of increased endothelial purinergic receptor density, or it may be due
      to stimulation and/or release of endothelial nitric oxide (NO) by TP.

PMID- 9602473
TI  - Changes in diastolic function and collagen content in normotensive and
      hypertensive rats with long-term streptozotocin-induced diabetes.
AB  - We investigated the relationship between left ventricular diastolic function and
      interstitial collagen content in the endocardium, mesocardium and epicardium of
      transverse sections of the heart, using an image analysis system in normotensive
      and hypertensive long-term streptozotocin (STZ) diabetic rats. STZ-induced
      diabetes was characterised by elevated blood glucose, polyuria, polydypsia and
      loss of body weight. In vivo systolic blood pressure was 165 +/- 4, 136 +/- 3 and
      129 +/- 7 mmHg in hypertensive and normotensive diabetic rats and age-matched
      controls, respectively. Heart rate was significantly lower (P < 0.01) in diabetic
      rats (283 +/- 8 and 280 +/- 10 beats min-1 in normotensive and hypertensive rats,
      respectively) than controls (393 +/- 18 beats min-1). Pressure-volume (P-V)
      curves were studied in isolated Langendorff perfused hearts at rest and after 20
      min global ischaemia and 30 min reperfusion 6 months after induction of diabetes.
      Left ventricular volumes were significantly smaller in diabetic rats than age
      matched controls, but volumes normalised for heart weight were higher in
      normotensive (by 28%) and hypertensive (by 10%) diabetic rats. Slopes of end
      diastolic P-V curves were similar between groups in basal conditions, but left
      ventricular systolic P-V curves were steeper in normotensive and flatter in
      hypertensive diabetic hearts. Post-ischaemic left ventricular end-diastolic
      pressure was significantly higher than the pre-ischaemic value at comparable
      increments of volume in each group. Collagen content significantly increased in
      the heart of rats with STZ-diabetes both in the free left ventricular wall and
      septum, and suggested this may play a role in the cardiac defects in
      contractility and relaxation in our experimental conditions. These results
      indicate that diabetes, irrespective of associated hypertension, can cause major
      changes in cardiac performance and susceptibility to ischaemia and reperfusion.

PMID- 9602474
TI  - The economic costs of alcohol abuse in Ontario.
AB  - The abuse of alcohol causes health and social problems, such as sickness, death,
      injury, pain, suffering and crime. These harms impose an economic burden on
      society. Resources are used or foregone as a consequence of alcohol abuse. This
      article provides an estimate of the economic cost of alcohol abuse in Ontario in
      1992. It uses the cost-of-illness method, in particular, the human-capital
      approach to estimate the prevalence-based economic costs of alcohol abuse. This
      methodology is consistent with international guidelines formulated at the 1994
      International Symposium on Economic and Social Costs of Substance Abuse. The
      direct and indirect economic costs of alcohol abuse are identified and estimated.
      The total economic cost of alcohol abuse, from a societal perspective, is
      estimated to be US$2261.10 million in Ontario in 1992.

PMID- 9602475
TI  - An evaluation of the Factor V Leiden mutation in a cohort of African-American
      pregnant women.
AB  - The objective of this work was to study the prevalence of the Factor V Leiden
      mutation in an obstetrical clinic largely comprised of African-American women. A
      cross-sectional study was performed evaluating a total of 231 consecutive women
      of African-American origin. Of these patients, 21 were considered at high risk
      for thrombosis, but none was found to carry the mutation. One patient (0.4 per
      cent) of the total was heterozygous for the Factor V Leiden mutation. African
      American women do not appear to be at an increased risk of being heterozygous or
      homozygous for the Leiden mutation. This low prevalence may be confounded by
      ascertainment bias in a population of pregnant women.

PMID- 9602476
TI  - Preliminary evidence for associations between second-trimester human chorionic
      gonadotropin and unconjugated oestriol levels with pregnancy outcome in Down
      syndrome pregnancies.
AB  - Fifty-six cases of Down syndrome were identified in a population of women who had
      undergone maternal serum triple marker screening [alpha-fetoprotein (AFP), human
      chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) analyses]. These
      affected pregnancies represented all known cases present in the population of
      34,368 women screened. Using a 1:270 mid-trimester Down syndrome risk to define
      the screen-positive group, 42 affected pregnancies were screen-positive (medians:
      AFP = 0.79 MOM, hCG = 2.13 MOM, uE3 = 0.62 MOM, age 34.6 years) and 14
      pregnancies were screen-negative (medians: AFP = 0.82 MOM, hCG = 1.57 MOM, uE3 =
      0.92 MOM, age 24.2 years). Four affected pregnancies were associated with in
      utero death and each of these cases was associated with relatively extreme values
      of AFP, hCG, and uE3, including the three highest levels of hCG in the entire
      series of Down syndrome pregnancies. Twenty-nine (15 screen-positive and 14
      screen-negative) affected pregnancies resulted in liveborns. Down syndrome
      pregnancies had a significantly shorter gestational term than controls, and Down
      syndrome babies were also lighter than controls, even after adjustment for sex
      and gestational age. In affected pregnancies, a low uE3 level appeared to be
      associated with a greater chance of a small-for-gestational age baby. No
      correlations could be demonstrated between AFP or hCG levels and gestational age
      adjusted term weight. Based on this small series, it would appear that uE3 may be
      particularly useful in detecting those Down syndrome cases associated with small
      for-gestational age fetuses. A very high hCG value may indicate a higher
      probability of fetal death.

PMID- 9602477
TI  - Intrauterine transfusions influence fetal leukocyte counts and subsets.
AB  - The objective of this study was to determine the effect of intravascular
      intrauterine transfusion (IUT) on fetal leukocyte counts and subsets. For this
      purpose, pre- and post-transfusion blood samples of 81 fetuses, receiving a total
      of 253 IUTs, were compared. Immediately after the IUT procedure an average
      decrease in fetal leukocyte count of 4 per cent was observed. When corrected for
      the dilutional effect of IUT, the average increase in leukocyte count was 41 per
      cent (n = 180), indicating that IUT resulted in a relative leukocytosis. This was
      in contrast to the statistically significant average decrease in platelet count
      of 62 per cent (P < 0.0001) immediately after IUT, suggesting that the relative
      increase in leukocyte count was lineage-specific. Differential leukocyte counts
      revealed that the changes in fetal leukocyte count, in terms of percentage, after
      IUT were the results of an increase in monocytes and basophils and a decrease in
      lymphocytes. Flow cytometric analysis demonstrated that the decrease in
      lymphocytes was evenly distributed among the different subpopulations and not the
      result of a specific down-regulation of one or more lymphocyte subsets. We
      observed only a modest relation between the duration of the transfusion and the
      degree of relative leukocytosis, suggesting that the onset of the leukocytosis
      probably occurred within minutes after the start of the transfusion. The observed
      effects appeared transient since the pre-transfusion leukocyte count between each
      consecutive IUT did not reveal significant alterations during the course of IUT
      treatment.

PMID- 9602478
TI  - Membrane thickness and PROM--high-frequency ultrasound measurements.
AB  - Premature rupture of the membranes (PROM) is still an unsolved problem in
      obstetrics. Neither prevention nor diagnosis nor therapy is readily available.
      The amniotic sac is stabilized mechanically by a dense network of collagenous
      fibres; in the event of PROM, the collagenous mesh is dissolved and the thickness
      of the amniotic sac is reduced. In a prospective study involving 32 patients, we
      measured the thickness of the membranes in vitro by high-frequency ultrasound and
      by light microscopy of histological sections, between gestational weeks 28 and
      32. We compared 18 patients with premature rupture of the amnio-chorionic
      membrane with 14 patients following induction of labour, with intact membranes at
      the same gestational age in vitro. We were able to show that the membrane in the
      PROM group (0.54 +/- 0.9 mm) was markedly thinner with fewer collagenous fibres
      than in the control group (0.74 +/- 1.01 mm). The application of high-frequency
      ultrasound in vivo in PROM may become helpful for the prediction of PROM; further
      studies are therefore desirable.

PMID- 9602479
TI  - Fetal intrahepatic hyperechogenic foci: prenatal ultrasound diagnosis and
      outcome.
AB  - Fetal intrahepatic hyperechogenic foci were found in seven out of 7260 patients
      (1:1037) referred to our prenatal centre for a fetal anomaly scan because of an
      increased risk or suspected presence of fetal structural anomalies. The
      gestational age varied between 20 and 32 weeks (mean 24 weeks). Fetal karyotyping
      in three out of seven fetuses resulted in one case of trisomy 18. Additional
      anomalies were diagnosed in both this case and a case of combined hyperechogenic
      liver foci, encephalocoele, and unilateral renal agenesis. TORCH and Parvo virus
      screening was only done in one patient and the results were negative. Outcome was
      normal in five fetuses with isolated intrahepatic lesions. In the presence of
      fetal intrahepatic hyperechogenic foci, a detailed scan of the entire fetus
      should be performed. Screening for infections should continue in order to clarify
      their role in the development of these intrahepatic lesions. Fetal karyotyping is
      recommended when additional structural anomalies are present. The outcome of
      fetuses with isolated hyperechogenic liver foci is generally good.

PMID- 9602480
TI  - Clinical significance of amniotic-fluid-cell culture failure.
AB  - Recent reports suggest an increased incidence of chromosomal abnormalities in
      pregnancies with amniotic fluid-cell culture failure. We retrospectively reviewed
      the cytogenetic results of 14,165 amniotic fluid samples processed in our
      laboratory from 1987 to 1996. Ninety-eight per cent of the samples were obtained
      before 24 weeks' gestation, mainly because of advanced maternal age; 2 per cent
      were obtained after or at 24 weeks because of the ultrasonographic finding of
      fetal structural defects. Amniotic-fluid-cell culture failure occurred in 62
      cases (0.44 per cent). Culture failure was more common in samples obtained after
      or at 24 weeks' gestation (10 per cent) than in those obtained before 24 weeks
      (0.27 per cent) (P < 0.001, chi-square test). This difference was also observed
      when the results were analysed according to the cases with known normal or
      abnormal karyotypes. The frequency of culture failure did not differ
      significantly between the groups with normal and abnormal karyotypes. We conclude
      that amniotic-fluid-cell culture failure is more common in advanced pregnancy
      with an ultrasonographic finding of fetal structural defects and is not
      associated with a higher incidence of chromosomal abnormalities.

PMID- 9602481
TI  - Awareness and use of prenatal diagnosis among Greek women: a national survey.
AB  - The prevention of genetic diseases through prenatal diagnosis depends to a large
      extent on the awareness and acceptance of available methods by the public. A
      national survey was conducted among Greek women in order to explore their
      attitudes towards and their use of prenatal diagnosis in relation to their
      lifestyle. The survey was originally addressed to 3000 Greek women 18-65 years of
      age. Using as a criterion having a child 5 years old or younger, 350 women were
      eligible for the study. It was noted that 52 per cent of the respondents were
      adequately informed, while 48 per cent had either superficial knowledge of the
      subject or no knowledge at all. Amniocentesis was the method that most women were
      familiar with. The majority said that they were informed by their doctors and the
      media, and 13 per cent of the participants had prenatal diagnosis during a
      previous pregnancy. Twenty-two per cent of those who were not tested were over 35
      years of age at the time of pregnancy. There was a significant positive
      correlation between awareness and acceptance of prenatal diagnosis, on the one
      hand, and the social, educational and financial profile of the women, on the
      other. Women aware of prenatal diagnosis adhered more closely to a healthy
      lifestyle and lived a family-centred life.

PMID- 9602482
TI  - Prenatal sonographic diagnosis of skeletal dysplasias--a report of the diagnostic
      and prognostic accuracy in 35 cases.
AB  - Sonographic assessment of the skeleton is a routine part of fetal anomaly
      scanning. We report a series of 35 cases seen during a 7-year interval in which a
      skeletal dysplasia was suspected prenatally. In seven (20 per cent) of the 35
      cases, a specific diagnosis could not be made either pre- or postnatally. Follow
      up was incomplete in one case. In 32 (91 per cent) of the 35 cases, prenatal
      sonographic examination correctly predicted the prognosis, although in only 11
      (31 per cent) of the 35 cases was the suggested prenatal diagnosis proven to be
      correct. The difficulty of making an accurate prenatal sonographic diagnosis in
      fetuses with suspected skeletal dysplasias throughout gestation, especially in
      the third trimester, and the importance of comprehensive multidisciplinary
      postnatal assessment in these cases are emphasized.

PMID- 9602483
TI  - B19 parvovirus induced fetal hydrops: rapid and simple diagnosis by detection of
      B19 antigens in amniotic fluids.
AB  - In our study we describe the direct detection of parvovirus B19 capsid antigens
      in amniotic fluid samples for the rapid and simple prenatal diagnosis of B19
      induced fetal hydrops. The assay was performed on amniotic fluid specimens from
      fetal hydrops dotted on nylon membranes. The two capsid antigens, VP1 and VP2,
      which represent four per cent and 96 per cent of the capsid, respectively, were
      detected using a pool of monoclonal antibodies directed against these two
      proteins and the complex was visualized by immunoperoxidase staining. The assay
      could be performed in about four hours and positive results were revealed at the
      end of the reaction as dark blue spots on the nylon membrane. We analysed 26
      amniotic fluid samples from 26 selected cases of non-immune hydrops for the
      presence of B19 antigens. Out of these 26 samples, 13 had previously proved
      positive for B19 DNA, detected by dot blot hybridization and/or in situ
      hybridization and/or nested PCR, and 13 had proved negative. The results obtained
      with our assay were compared with results obtained for the presence of B19 DNA
      and a close agreement was found. The method is simple and rapid to perform, does
      not require costly instruments, and all the reagents used in the assay are
      commercially available. The assay described can thus be useful for a prompt
      counselling and management of B19 fetal infection.

PMID- 9602484
TI  - Prenatal diagnosis of Smith-Lemli-Opitz syndrome.

PMID- 9602485
TI  - Prenatal diagnosis of an epidermal scalp cyst simulating an encephalocoele.
AB  - The majority of extracranial masses detected by prenatal ultrasound screening are
      encephalocoeles. Several recent publications have drawn attention to extracranial
      masses which resemble encephalocoeles. The uncertainty in these situations can
      result in the unnecessary termination of a pregnancy. We report a case of an
      epidermal cyst of the scalp presenting as an encephalocoele at a routine second
      trimester ultrasound scan.

PMID- 9602486
TI  - Case report: prenatal diagnosis of diastrophic dysplasia by ultrasound at 21
      weeks of gestation in a mother with massive obesity.
AB  - Routine prenatal ultrasound of a massively obese mother at 21 weeks of gestation
      revealed short-limb dwarfism in the fetus. The proportionate shortening of
      tubular bones of about 50 per cent of the normal length, the absence of thoracic
      dysplasia, and a normal head circumference narrowed the diagnosis down to a
      severe but non-lethal skeletal dysplasia. Ulnar deviation of the hands and
      talipes made diastrophic dysplasia the most likely differential diagnosis. At
      post-mortem clinical examination, the diagnosis of diastrophic dysplasia was
      clearly apparent due to highly specific 'hitch-hiker thumbs', similarly luxated
      big toes, facial dysmorphism, and a cleft palate. Retrospective re-evaluation of
      the prenatal ultrasound videos revealed the misplaced thumbs, which together with
      the ulnar deviation of the wrist and suspected talipes, led to the conclusion
      that the definitive diagnosis can be established prenatally, even in a mother
      with massive obesity.

PMID- 9602487
TI  - Prenatal confirmation of true fetal trisomy 22 mosaicism by fetal skin biopsy
      following normal fetal blood sampling.
AB  - Trisomy 22 mosaicism diagnosed at 20 weeks' gestation by amniocentesis in a 35
      year-old woman was not confirmed by fetal blood sampling. Subsequent fetal skin
      biopsy revealed trisomy 22 in 7 of the 15 fibroblasts analysed. We conclude that,
      depending on the chromosome involved, fetal skin biopsy should be considered in
      the diagnostic work-up when mosaicism is found in amniotic fluid.

PMID- 9602488
TI  - Detection of translocations involving the Y-chromosome in prospective prenatal
      screening of common chromosomal aneuploidies by FISH.
AB  - In the application of the fluorescence in situ hybridization (FISH) technique for
      prospective prenatal screening of common aneuploidies involving the autosomes 13,
      18, and 21, and sex chromosomes, six cases of inconsistency between the results
      of FISH analysis and the results of karyotyping of cultured amniocytes have been
      observed, including two cases of translocation involving the Y-chromosome and
      chromosome 15 in a total of 904 cases of amniocentesis studied. In one case, the
      translocation was of maternal origin, and in the other, of paternal origin. In
      both cases, the couples decided to continue the pregnancy and normal babies were
      delivered. The data show the usefulness of applying the FISH technique in
      prospective prenatal screening of common trisomies for the possible detection of
      rare chromosome rearrangements involving the Y-chromosome.

PMID- 9602489
TI  - Prenatal diagnosis of de novo isochromosome 13q associated with microcephaly,
      alobar holoprosencephaly and cebocephaly in a fetus.
AB  - We report on the prenatal diagnosis, genetic studies, and pathology of a case
      with de novo isochromosome 13q. A 31-year-old primigravida was referred for
      genetic counselling at 26 weeks' gestation due to the sonographic findings of
      intrauterine growth retardation and microcephaly. Level II ultrasonograms further
      demonstrated alobar holoprosencephaly, hypotelorism, polydactyly, a ventricular
      septal defect, and a single nostril. A diagnosis of cebocephaly was made. Genetic
      amniocentesis and cord blood sampling revealed translocation trisomy 13 with a de
      novo t(13q13q) rearrangement. Chromosomal analysis using G- and C-banding
      techniques and fluorescence in situ hybridization (FISH) showed an apparent
      monocentric isochromosome. Molecular analyses using polymorphic molecular markers
      showed that the rearrangement was consistent with an isochromosome of maternal
      chromosome 13q[46,XX,i(13)(q10)]. Necropsy confirmed cebocephaly and the
      prenatally detected anomalies.

PMID- 9602490
TI  - High resolution chromosome analysis and in situ hybridization on amniotic fluid
      for diagnosis of a cryptic translocation.
AB  - We report a cryptic translocation ascertained in a family after the birth of a
      mentally retarded proband. High resolution chromosome examination revealed that
      the father had a subtle translocation between chromosome 5 and chromosome 13, 46,
      XY, t(5;13) (q35.2;q34). Two specific, non-routine techniques were associated for
      prenatal diagnosis: high resolution cytogenetic studies on the amniotic fluid and
      fluorescent in situ hybridization with YACs as specific telomeric probes. The
      fetus had the same cryptic translocation as his father.

PMID- 9602491
TI  - Early amniocentesis versus chorionic villus sampling.

PMID- 9602492
TI  - Prenatal diagnosis of congenital toxoplasmosis by PCR: extended experience.

PMID- 9602493
TI  - Isoenzymes of maternal serum alkaline phosphatase in Down syndrome.

PMID- 9602494
TI  - Prenatal diagnosis of homozygous alpha-thalassaemia-1.

PMID- 9602495
TI  - Prenatal detection of a deletion 22q11 by FISH.

PMID- 9602497
TI  - Current awareness in prenatal diagnosis.

PMID- 9602496
TI  - The accuracy of assigned risks in maternal serum screening.

PMID- 9602498
TI  - Central neuron-glial and glial-glial interactions following axon injury.
AB  - Axon injury rapidly activates microglial and astroglial cells close to the
      axotomized neurons. Following motor axon injury, astrocytes upregulate within
      hour(s) the gap junction protein connexin-43, and within one day glial fibrillary
      acidic protein (GFAP). Concomitantly, microglial cells proliferate and migrate
      towards the axotomized neuron perikarya. Analogous responses occur in central
      termination territories of peripherally injured sensory ganglion cells. The
      activated microglia express a number of inflammatory and immune mediators. When
      neuron degeneration occurs, microglia act as phagocytes. This is uncommon after
      peripheral nerve injury in the adult mammal, however, and the functional
      implications of the glial cell responses in this situation are unclear. When
      central axons are injured, the glial cell responses around the affected neuron
      perikarya appears to be minimal or absent, unless neuron degeneration occurs.
      Microglia proliferate, and astrocytes upregulate GFAP along central axons
      undergoing anterograde, Wallerian, degeneration. Although microglia develop into
      phagocytes, they eliminate the disintegrating myelin very slowly, presumably
      because they fail to release molecules which facilitate phagocytosis. During
      later stages of Wallerian degeneration, oligodendrocytes express clusterin, a
      glycoprotein implicated in several conditions of cell degeneration. A
      hypothetical scheme for glial cell activation following axon injury is discussed,
      implying the injured neurons initially interact with adjacent astrocytes.
      Subsequently, neighbouring resting microglia are activated. These glial reactions
      are amplified by paracrine and autocrine mechanisms, in which cytokines appear to
      be important mediators. The specific functional properties of the activated glial
      cells will determine their influence on neuronal survival, axon regeneration, and
      synaptic plasticity. The control of the induction and progression of these
      responses are therefore likely to be critical for the outcome of, for example,
      neurotrauma, brain ischemia and chronic neurodegenerative diseases.

PMID- 9602499
TI  - Pathophysiological mechanisms of genetic absence epilepsy in the rat.
AB  - Generalized non-convulsive absence seizures are characterized by the occurrence
      of synchronous and bilateral spike and wave discharges (SWDs) on the
      electroencephalogram, that are concomitant with a behavioral arrest. Many
      similarities between rodent and human absence seizures support the use of genetic
      rodent models, in which spontaneous SWDs occur. This review summarizes data
      obtained on the neurophysiological and neurochemical mechanisms of absence
      seizures with special emphasis on the Genetic Absence Epilepsy Rats from
      Strasbourg (GAERS). EEG recordings from various brain regions and lesion
      experiments showed that the cortex, the reticular nucleus and the relay nuclei of
      the thalamus play a predominant role in the development of SWDs. Neither the
      cortex, nor the thalamus alone can sustain SWDs, indicating that both structures
      are intimely involved in the genesis of SWDs. Pharmacological data confirmed that
      both inhibitory and excitatory neurotransmissions are involved in the genesis and
      control of absence seizures. Whether the generation of SWDs is the result of an
      excessive cortical excitability, due to an unbalance between inhibition and
      excitation, or excessive thalamic oscillations, due to abnormal intrinsic
      neuronal properties under the control of inhibitory GABAergic mechanisms, remains
      controversial. The thalamo-cortical activity is regulated by several
      monoaminergic and cholinergic projections. An alteration of the activity of these
      different ascending inputs may induce a temporary inadequation of the functional
      state between the cortex and the thalamus and thus promote SWDs. The experimental
      data are discussed in view of these possible pathophysiological mechanisms.

PMID- 9602500
TI  - A structural basis for memory storage in mammals.
AB  - It is proposed that altered dendrite length and de novo formation of new dendrite
      branches in cholinoceptive cells are responsible for long-term memory storage, a
      process enabled by the degradation of microtubule-associated protein-2. These
      memories are encoded as modality-specific associable representations.
      Accordingly, associable representations are confined to cytoarchitectonic modules
      of the cerebral cortex, hippocampus, and amygdala. The proposed sequence of
      events leading to long-term storage in cholinoceptive dendrites begins with
      changes in neuronal activity, then in neurotrophin release, followed by enhanced
      acetylcholine release, muscarinic response, calcium influx, degradation of
      microtubule-associated protein-2, and finally new dendrite structure.
      Hypothetically, each associable representation consists of altered dendrite
      segments from approximately 5000-15,000 cholinoceptive cells contained within one
      or a few module(s). Simultaneous restructuring during consolidation of long-term
      memory is hypothesized to result in a similar infrastructure among dendrite sets,
      facilitating co-activation of those dendrite sets by neurotransmitters such as
      acetylcholine, and conceivably enabling high energy interactions between those
      dendrites by phenomena such as quantum optical coherence. Based on the specific
      architecture proposed, it is estimated that the human telecephalon contains
      enough dendrites to encode 50 million associable representations in a lifetime,
      or put another way, to encode one new associable representation each minute. The
      implications that this proposal has regarding treatments for Alzheimer's disease
      are also discussed.

PMID- 9602501
TI  - Long-term depression of synaptic transmission in the cerebellum: cellular and
      molecular mechanisms revisited.
AB  - Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)
      Purkinje cell (PC) synapses in the cerebellum has been the first established
      example of enduring decrease of synaptic efficacy in the central nervous system.
      This review focuses on the underlying cellular and molecular mechanisms. Thus, at
      the level of the postsynaptic membranes of PCs, induction of LTD requires
      concommitent activation of voltage-gated calcium channels (VGCCs) and of
      ionotropic and metabotopic glutamate receptors, of the alpha-amino-3 hydroxy-5
      methyl-isoxalone-4-propionate (AMPA) and mGluR1 alpha types respectively.
      Subsequent intracellular cascades involve production of nitric oxide from
      arginine and of cGMP, activation of phospholipase A2 and of several protein
      kinases including protein kinase C and tyrosine kinases. Activation of protein
      kinase G and of phosphatases are also likely to be involved in LTD induction. In
      contrast, there are still uncertainties concerning a major role of release of
      calcium from internal stores in LTD induction. Finally protein synthesis is
      required for a late phase of LTD to occur. All available experimental evidence
      points towards a postsynaptic site for LTD expression. In particular,
      electrophysiological data demonstrate a genuine modification of the functional
      properties of AMPA receptors of PCs during LTD, and immunocytochemical evidence
      suggests that this might result from a phosphorylation of these receptors.

PMID- 9602502
TI  - Nitric oxide synthesis during acute SIV mac251 infection of macaques.
AB  - During HIV1 infection, nitric oxide (NO) could significantly contribute to immune
      dysregulation by its multiple effects on the modulation of the host immune
      response. The in vivo regulation of NO production is attributable to several
      nitric oxide synthases, one of which is a cytokine-inducible enzyme (iNOS). In
      vitro experiments suggest that iNOS expression in macrophages may be directly
      modulated by HIV infection. Acute infection of macaques with a pathogenic strain
      of the simian immunodeficiency virus (SIV) represents a relevant animal model for
      the in vivo study of the relationships between iNOS expression and lentiviral
      replication. Indeed, acute infection in this model is characterized by high rates
      of viral replication associated with early cytokine dysregulations, in the
      absence of opportunistic infection. In our experiment, two cynomolgus macaques
      were inoculated intravenously with a pathogenic isolate of SIVmac251, and iNOS
      gene expression was investigated ex vivo during acute infection in mononuclear
      cells obtained from bronchoalveolar lavage (BALMCs). An enhancement of this gene
      expression was observed as early as the second week of infection, at the time of
      peak of systemic viraemia, and increased until day 31 p.i. This overexpression
      was concomitant with a marked linear increase in IFN gamma expression in BALMCs.
      At the time of systemic viral load peak, the production of NO in plasma of these
      two monkeys was evidenced by the detection of large amounts of nitrate.

PMID- 9602503
TI  - A restriction cleavage and transfection system for introducing foreign DNA
      sequences into the genome of a herpesvirus.
AB  - This report describes a simple and efficient system for construction of
      recombinant pseudorabies (Aujeszky's disease) virus (PrV) which is based on the
      use of a unique restriction site inserted into the viral genome. This system
      enables the recovery of genetically modified viruses without screening or
      selection for a specific phenotype, since practically all mature viral particles
      obtained carry the foreign sequences. To demonstrate, we introduced the tumour
      suppressor protein-53 (p53) gene into two different intergenic locations of PrV:
      the ribonucleotide reductase (rr) gene and the promoter of a putative latency
      gene (PLAT), located at the inverted repeat (IR) region of the viral genome. As a
      first step, we engineered a unique EcoRI recognition site into the rr gene or
      into both copies of PLAT with the help of marker transfer using the bacterial
      lacZ gene. Then, in both cases viral DNAs were cut with the restriction
      endonuclease EcoRI followed by treatment with calf intestinal phosphatase and
      used for cotransfection into porcine kidney cells with a plasmid containing the
      p53 gene flanked by viral DNAs homologous to the target region. As a result of
      this process, in most of the experiments, we obtained recombinant viruses without
      the background of parental viruses. Here we show that this method can be used for
      directional insertion of exogenous sequences into either the unique or the IR
      region of the PrV chromosome. In principle, this system should be applicable to
      the construction of recombinant derivatives of any viruses having infectious DNA.

PMID- 9602504
TI  - HNF1 is critical for the liver-specific function of HBV enhancer II.
AB  - Hepatitis B virus (HBV) is a hepatotropic virus and its gene expression is highly
      liver-specific. It has been reported that the function of enhancer II (ENII) and
      the core and the core promoter (Cp) of HBV has a hepatocyte preference. To
      understand the effects of liver-specific nuclear factors on ENII, in this report,
      hepatocyte nuclear factor 1 (HNF1) was investigated for its possible action on
      ENII function. It was found that HNF1 transactivates ENII/Cp in HeLa cells, and
      antisense HNF1 suppresses it in HepG2 cells. Deletion analysis revealed that the
      B element of ENII is the target region responsible for the regulation of HNF1.
      Sequence alignment suggested the presence of the potential HNF1 binding sites in
      the B element of ENII. The results of electrophoresis mobility shift assay
      indicated that the B2 region could specifically bind a GST-HNF1 fusion protein
      and could compete with binding of HNF1 to the consensus motif in the rat beta
      fibrinogen promoter, suggesting that the major binding site of HNF1 is located in
      the B2 region. Our results demonstrate that HNF1 is one of the important
      regulatory factors for the liver-specific function of HBV and that it
      transregulates ENII activity via direct binding to B2.

PMID- 9602505
TI  - A fifth human cytomegalovirus glycoprotein B genotype.
AB  - Genetic variation in glycoprotein B (gB) may play a role in human cytomegalovirus
      (HCMV) pathogenesis. Using restriction endonuclease digestion and DNA sequencing,
      a unique gB genotype was identified in eight HCMV strains isolated from five
      patients with the acquired immune deficiency syndrome. Nucleic acid homology to
      the four previously described gB genotypes ranged from 79 to 91% for the two
      major variable regions of gB. Studies of the role of gB in HCMV pathogenesis
      should recognize the existence of live gB genotypes.

PMID- 9602506
TI  - Amplification and detection of the terminal 3' non-coding region of hepatitis C
      virus isolates.
AB  - A reverse transcription polymerase chain reaction (RT-PCR) assay was set up to
      amplify, from chronically infected patients, the recently discovered hepatitis C
      virus (HCV) 3'non-coding region (3'NCR). A panel of 149 samples was tested by RT
      PCR for the 3'NCR. Two detection methods of amplified products were evaluated:
      ethidium bromide staining on 3% agarose gel electrophoresis and DNA enzyme
      immunoassay ("DEIA"). Results were compared with those obtained by amplification
      of the 5' non-coding region (5'NCR), i.e. the "Amplicor" HCV RNA qualitative
      assay. Genotype distribution of the 86 Amplicor-positive samples was subtype 1a:
      n = 15 (17.4%); subtype 1b: n = 32 (37.2%); subtype 2a/2c: n = 7 (8.1%); type 3:
      n = 25 (29%); type 4: n = 2 (2.3%); type 5: n = 1 (1.2%); not determined: n = 4
      (2.3%). Sixty-three sera were HCV RNA-Amplicor-negative, 32 of which were from
      HCV-seronegative patients and 31 from HCV-seropositive patients. All seronegative
      samples were negative by both PCR methods. None of the Amplicor-negative samples
      from seropositive patients were positive by the 3'NCR assay. Forty-seven (54.7%)
      and 83 (96.5%) of the 86 Amplicor-HCV-RNA-positive samples were positive after
      ethidium bromide staining and by the 3'NCR assay using DEIA, respectively. The
      limit of detection by end-point dilution was lower with Amplicor. No difference
      between genotypes was detected for the 3'NCR RT-PCR, and a high degree of
      concordance was obtained between the Amplicor and the 3'NCR DEIA results (97.4%).
      Nevertheless, further studies are needed before the 3'NCR RT-PCR assay could be
      used instead of the 5'NCR RT-PCR for diagnostic purposes.

PMID- 9602507
TI  - Weight gain associated with protease inhibitor therapy in HIV-infected patients.
AB  - Weight loss and wasting are significant complications of HIV disease. HIV
      protease inhibitor therapy promotes clinical, immunologic and virologic
      improvement in HIV-infected patients. In this study, we sought to determine the
      specific effect of HIV protease inhibitors on patient weight. Ten consecutive HIV
      patients were treated with protease inhibitor-containing regimens over six
      months. CD4 T-cell counts, plasma viral load levels and bariatric changes were
      monitored during the study. Patients experienced a mean weight gain of 19 Pounds
      (P = 0.006). There was a significant increase in mean CD4 T-cell count (P =
      0.008) and a significant decrease in mean viral load level (P = 0.004). The
      increase in CD4 T cells did not correlate with weight gain, whereas the decrease
      in viral load did show a significant correlation with the weight increase (P =
      0.003). The mechanism of protease inhibitor-induced weight gain is discussed. The
      medications may also be useful for wasting diseases unrelated to HIV.

PMID- 9602508
TI  - [Influenza A(H5N1) in Hong Kong: forerunner of a pandemic or an only
      scientifically interesting phenomenon and a useful exercise in pandemiology?].
AB  - From a three-year old boy in Hong Kong who died in May 1997 with an extensive
      influenza pneumonia an influenza A virus has been isolated which was, first at
      the National Influenza Centre of the Netherlands, identified as belonging to
      subtype H5N1. Presumably the patient had acquired the infection directly from an
      outbreak of fowl plague among chickens. As far as is known this is the first case
      of the isolation of an influenza virus belonging to one of the subtypes H4-H15
      from a human influenza patient. At the end of 1997 seventeen more cases of human
      A (H5N1) influenza have been detected in Hong Kong, including five fatal cases.
      Genetic analyses of seven of these virus isolates did not reveal the occurrence
      of reassortment with a human or porcine influenza virus, which could have
      rendered the virus potentially pandemic. Man-to-man transmission of the virus has
      not been demonstrated but cannot be excluded either. This event has shown that
      the WHO surveillance of influenza viruses, although perhaps not perfect, has
      functioned well.

PMID- 9602509
TI  - [BVD outbreak can be costly: a case report].
AB  - The losses caused by an BVD-outbreak on a Dutch dairy farm with approximately 100
      dairy cows were determined. In this particular farm, calves which were born
      around the same time as a detected carrier calf were not sampled. These carrier
      calves were kept on as replacement heifers and caused additional loss on top of
      the losses already caused by the primary outbreak. The total economic loss was
      more than f 96.000,- or nearly f 1000,-per cow. This case report illustrates the
      potential for serious economic loss when an BVD free herd is reinfected combined
      with less adequate control measures.

PMID- 9602510
TI  - [Pioneers: veterinarians from earlier times (27). William Moorcroft (1767-1825)].

PMID- 9602511
TI  - [2nd round-table discussion GPGH on education. Group Practitioners Large Domestic
      Animals].

PMID- 9602512
TI  - Diagnosis of toxoplasma abortion in ewes by polymerase chain reaction.
AB  - Eighteen oestrus-synchronised ewes were infected experimentally with 1500
      sporulated oocysts of Toxoplasma gondii between 80 and 90 days of gestation. The
      infection induced pyrexia and specific antibody in all the ewes. One ewe resorbed
      its fetus, five ewes aborted and 12 delivered live, congenitally-infected lambs
      whose pre-colostral serum was antibody-positive. Tissues from the aborted fetuses
      and placentae from the live lambs were examined for toxoplasma infection by
      polymerase chain reaction (PCR) amplification of the B1 gene and by mouse
      inoculation. Using a simple protocol of tissue preparation without DNA extraction
      and a nested format, PCR was as sensitive as mouse inoculation. Placental
      cotyledon gave a higher sensitivity of detection than brain, lung or liver, and
      16 of 19 placentae were positive by PCR compared with 13 of 18 by mouse
      inoculation. In mock-infected tissues, as few as 10 tachyzoites could be
      detected. The PCR could be applied to tissues unfit for mouse inoculation.

PMID- 9602513
TI  - Choosing appropriate space allowances for slaughter pigs transported by road: a
      review.
AB  - In the United Kingdom pigs can spend up to 11 hours in transit to slaughter but
      on average travel for two to three hours. In the past, international journeys
      have lasted up to 40 hours and have been over 900 miles long. There is evidence
      that pigs, like calves and sheep, but unlike adult cattle, prefer to lie down if
      provided with suitable conditions, particularly bedding, on the vehicle. They
      will, however, sometimes stand during short journeys, possibly when excessive
      vibration or uncomfortable flooring, particularly a lack of sufficient bedding,
      cause discomfort. Current UK legislation and EU Directive 95/29/EC specify that,
      in general, pigs must have sufficient space to lie down during transit.
      Measurements of the space needed for sternal recumbency, and direct observations
      of pigs at different stocking densities, suggest that the minimum space required
      is equivalent to about 250 kg/m2 for normal slaughter pigs of 90 to 100 kg
      liveweight. This figure may not be appropriate for very small or very large pigs.
      In the UK at present, more than half of all slaughter pigs are transported at
      densities greater than that prescribed (235 kg/m2) in the EU Directive. At
      stocking densities above about 250 kg/m2 there may not be enough room available
      for all the pigs to lie down, leading to continual disturbance of recumbent
      animals by those seeking a place to rest. A stocking density of 322 kg/m2 leads
      to clear evidence of physical stress. During long journeys (> or = 25 hours) meat
      quality is reduced by high stocking densities, implying muscle glycogen depletion
      and possibly fatigue. Higher stocking densities are also associated with higher
      mortality. There is evidence of wide variations in air temperature inside
      transporters, particularly for international journeys. Although there are small
      variations within vehicles, the temperature of the air inside is closely related
      to the outside temperature. It has been recommended that the temperature within
      the vehicle should not exceed 30 degrees C in order to remain within the pig's
      thermoneutral zone. Such temperatures, together with acceptably low
      concentrations of potentially noxious gases, such as carbon dioxide, can be
      achieved in moving vehicles by adequate ventilation, provided there is adequate
      space above the animals' heads. In triple-decked lorries, the height between
      decks has tended to be reduced and can be as little as 90 cm. Further work is
      needed to decide whether this is sufficient for modern slaughter pigs.

PMID- 9602514
TI  - Craniomandibular osteopathy in two Pyrenean mountain dogs.
AB  - Craniomandibular osteopathy was diagnosed in two Pyrenean mountain dogs with a
      history of mandibular swelling, pain, fever and, in dog 1, lameness. Radiographs
      demonstrated extensive, active new bone formation on the ventral aspect of the
      mandibular bodies of both dogs. Dog 2 responded well to treatment but dog 1 was
      euthanased owing to severe pain, dysphagia and unsuccessful treatment. The
      mandibles were examined by means of back-scattered scanning electron microscopy
      and a well arranged mineralised trabecular network of chondroid tissue and woven
      bone was observed. The mandibular cortical bone under the areas of periosteal
      proliferation was also affected, showing a looseness of the characteristic
      compact appearance of lamellar bone. This is the first report of craniomandibular
      osteopathy in this breed.

PMID- 9602515
TI  - Aorto-iliac thrombosis in a foal.
AB  - A six-day-old Missouri foxtrotter colt was examined because it had had diarrhoea
      since it was 24 hours old. A diagnosis of colitis, septicaemia, and disruption of
      the arterial blood flow to the pelvic limbs was made on the basis of clinical and
      laboratory findings. Despite intensive medical therapy, the foal died 13 hours
      after being examined. Postmortem examination revealed diffuse fibrinous enteritis
      with lymphoid necrosis, multifocal fibrinonecrotic typhlocolitis, disseminated
      intravascular coagulation, and a large occluding thrombus at the aortic
      termination. The results of bacteriological culturing supported the diagnosis of
      septicaemia leading to activation of the clotting cascade, disseminated
      intravascular coagulation, aorto-iliac thrombosis and infarction of the pelvic
      limbs.

PMID- 9602516
TI  - Outbreaks of stringhalt in southern Chile.

PMID- 9602517
TI  - Comparative efficacy of a new oxfendazole pour-on in cattle.

PMID- 9602518
TI  - British Cattle Movement Service: registering as an agent.

PMID- 9602519
TI  - Novel porcine circoviruses from pigs with wasting disease syndromes.

PMID- 9602520
TI  - Population density and infectious disease at bird tables.

PMID- 9602521
TI  - Tail-biting and tail-docking in pigs.

PMID- 9602522
TI  - Tests of a linear model of visual-vestibular interaction using the technique of
      parameter estimation.
AB  - The goal of this study was to test whether a superposition model of smooth
      pursuit and vestibuloocular reflex (VOR) eye movements could account for the
      stability of gaze that subjects show as they view a stationary target, during
      head rotations at frequencies that correspond to natural movements. Horizontal
      smooth-pursuit and the VOR were tested using sinusoidal stimuli with frequencies
      in the range 1.0-3.5 Hz. During head rotation, subjects viewed a stationary
      target either directly or through an optical device that required eye movements
      to be approximately twice the amplitude of head movements in order to maintain
      foveal vision of the target. The gain of compensatory eye movements during
      viewing through the optical device was generally greater than during direct
      viewing or during attempted fixation of the remembered target location in
      darkness. This suggests that visual factors influence the response, even at high
      frequencies of head rotation. During viewing through the optical device, the gain
      of compensatory eye movements declined as a function of the frequency of head
      rotation (P < 0.001) but, at any particular frequency, there was no correlation
      with peak head velocity 9P > 0.23), peak head acceleration (P > 0.22) or retinal
      slip speed (P > 0.22). The optimal values of parameters of smooth-pursuit and VOR
      components of a simple superposition model were estimated in the frequency
      domain, using the measured responses during head rotation, as each subject viewed
      the stationary target through the optical device. We then compared the model's
      prediction of smooth-pursuit gain and phase, at each frequency, with values
      obtained experimentally. Each subject's pursuit showed lower gain and greater
      phase lag than the model predicted. Smooth-pursuit performance did not improve
      significantly if the moving target was a 10 deg x 10 deg Amsler grid, or if
      sinusoidal oscillation of the target was superimposed on ramp motion. Further,
      subjects were still able to modulate the gain of compensatory eye movements
      during pseudo-random head perturbations, making improved predictor performance
      during visual-vestibular interactions unlikely. We conclude that the increase in
      gain of eye movements that compensate for head rotations when subjects view,
      rather than imagine, a stationary target cannot be adequately explained by
      superposition of VOR and smooth-pursuit signals. Instead, vision may affect VOR
      performance by determining the context of the behavior.

PMID- 9602523
TI  - Learning and stabilization of altruistic behaviors in multi-agent systems by
      reciprocity.
AB  - Optimization of performance in collective systems often requires altruism. The
      emergence and stabilization of altruistic behaviors are difficult to achieve
      because the agents incur a cost when behaving altruistically. In this paper, we
      propose a biologically inspired strategy to learn stable altruistic behaviors in
      artificial multi-agent systems, namely reciprocal altruism. This strategy in
      conjunction with learning capabilities make altruistic agents cooperate only
      between themselves, thus preventing their exploitation by selfish agents, if
      future benefits are greater than the current cost of altruistic acts. Our multi
      agent system is made up of agents with a behavior-based architecture. Agents
      learn the most suitable cooperative strategy for different environments by means
      of a reinforcement learning algorithm. Each agent receives a reinforcement signal
      that only measures its individual performance. Simulation results show how the
      multi-agent system learns stable altruistic behaviors, so achieving optimal (or
      near-to-optimal) performances in unknown and changing environments.

PMID- 9602524
TI  - A locally inhibited lateral neural network: on the fundamental features of a
      network consisting of neurons with a restricted range of interaction.
AB  - A network model that consists of neurons with a restricted range of interaction
      is presented. The neurons are connected mutually by inhibition weights. The
      inhibition of the whole network can be controlled by the range of interaction of
      a neuron. By this local inhibition mechanism, the present network can produce
      patterns with a small activity from input patterns with various large activities.
      Moreover, it is shown in simulation that the network has attractors for input
      patterns. The appearance of attractors is caused by the local interaction of
      neurons. Thus, we expect that the network not only works as a kind of filter, but
      also as a memory device for storing the produced patterns. In the present paper,
      the fundamental features and behavior of the network are studied by using a
      simple network structure and a simple rule of interaction of neurons. In
      particular, the relation between the interaction range of a neuron and the
      activity of input-output patterns is shown in simulation. Furthermore, the limit
      of the transformation and the size of basin are studied numerically.

PMID- 9602525
TI  - Quantification of emotion by nonlinear analysis of the chaotic dynamics of
      electroencephalograms during perception of 1/f music.
AB  - The goal of this study is to quantify and determine the way in which the
      emotional response to music is reflected in the electrical activities of the
      brain. When the power spectrum of sequences of musical notes is inversely
      proportional to the frequency on a log-log plot, we call it 1/f music. According
      to previous research, most listeners agree that 1/f music is much more pleasing
      than white (1/f0) or brown (1/f2) music. Based on these studies, we used
      nonlinear methods to investigate the chaotic dynamics of electroencephalograms
      (EEGs) elicited by computer-generated 1/f music, white music, and brown music. In
      this analysis, we used the correlation dimension and the largest Lyapunov
      exponent as measures of complexity and chaos. We developed a new method that is
      strikingly faster and more accurate than other algorithms for calculating the
      nonlinear invariant measures from limited noisy data. At the right temporal lobe,
      1/f music elicited lower values of both the correlation dimension and the largest
      Lyapunov exponent than white or brown music. We observed that brains which feel
      more pleased show decreased chaotic electrophysiological behavior. By observing
      that the nonlinear invariant measures for the 1/f distribution of the rhythm with
      the melody kept constant are lower than those for the 1/f distribution of melody
      with the rhythm kept constant, we could conclude that the rhythm variations
      contribute much more to a pleasing response to music than the melody variations
      do. These results support the assumption that chaos plays an important role in
      brain function, especially emotion.

PMID- 9602526
TI  - An equivalent cable model for neuronal trees with active membrane.
AB  - A non-uniform equivalent cable model of membrane voltage changes in branching
      neuronal trees with active ion channels has been developed. A general branching
      condition is formulated, extending Rall's 3/2 power rule for passive dendritic
      trees so that non-uniform cable segments can be treated. The theoretical results
      support the use of the dendritic profile model of Clements and Redman. The theory
      is then applied to dendrites of different morphological type yielding qualitative
      different response behaviour.

PMID- 9602527
TI  - Spherulitic brushite stone in the dental pulp of a cow.
AB  - Pulp stones of human teeth usually contain biological apatite. In the dental pulp
      of a cow, aged 12 years, we observed spherulitic pulp stones, up to approximately
      200 microns in diameter, consisting of radially arranged crystals with several
      kinds of light microscopy and scanning electron microscopy including the
      secondary electron and the backscattered electron signals. The crystals extending
      fan-like towards the periphery showed a rectangular shape, and they had subunits
      of elongated crystallites and fine slits of NaOCl-dissolved substances, probably
      including organic matter and amorphous mineral. By using energy-dispersive X-ray
      microanalysis, large amounts of Ca and P, and trace elements of Na, Mg, Cl, and
      Fe were detected from the stones. The calcium phosphate crystals were identified
      as biological brushite by shape, Ca/ P molar ratio, and electron diffraction
      pattern. Core regions of the stones containing granular structures, probably
      erythrocytes, were always present in blood vessels, and rectangular crystals
      frequently penetrated the vessel walls. Under the decalcified sections, the nidi
      were completely or incompletely dissolved, but the peripheries showed a radial
      arrangement of erythrocytes. Thus, the nidi may be thrombus or necrotic blood
      cells including erythrocytes. Such calcospherulites in the dental pulp of a cow
      were similar to the spherulitic pulp stones in human deciduous teeth reported
      previously, however, their nidi were present in different regions.

PMID- 9602528
TI  - Scanning electron microscopic study of flowing erythrocytes in hepatic sinusoids
      as revealed by 'in vivo cryotechnique'.
AB  - The purpose of this study is to develop a method for stabilizing erythrocytes
      under flowing condition in living livers, as revealed by scanning electron
      microscopy (SEM). After the procedure of the 'in vivo cryotechnique', both freeze
      substitution and subsequent t-butyl alcohol freeze-drying methods were used for
      preparing SEM specimens. By freeze-fracturing with a scalpel in liquid nitrogen
      before the freeze-substitution, better preserved surface tissues were obtained
      for examination. Erythrocytes in hepatic sinusoids were clearly detected without
      plasma components by the freeze-substitution method, and well preserved in parts
      where they were flowing with their original shapes. Some were accumulated in
      sinusoids, especially injunctioning areas of sinusoidal networks, as compared
      with those in narrow lumens between hepatocyte plates. Shapes of such
      erythrocytes were various, locating along endothelial cells. After stopping the
      blood supply into livers by artificial cardiac arrest, their shapes were
      dramatically changed into biconcaves and they became aggregated side by side to
      be packed in the sinusoids. The three-dimensional shapes of flowing erythrocytes
      in hepatic sinusoids were demonstrated for the first time by the 'in vivo
      cryotechnique' combined with SEM.

PMID- 9602529
TI  - Classification of the frog lingual gland cells and their exocytotic features.
AB  - We examined under light and electron microscopes the frog lingual gland before
      and after acetylcholine-stimulation. The lingual gland is composed of five kinds
      of secretory cells (type 1-5) and ciliated cells. Each secretory cell had
      numerous cell-type characteristic secretory granules, probably in which both
      serous and mucous secretory products were contained. The ciliated cells had
      lysosomes, cytoplasmic filaments and on their apical surface microvilli in
      addition to cilia. Two kinds of exocytotic features were demonstrated in the
      secretory cells. One of them, termed multigranular exocytosis, was whole-cell
      discharge of secretory products in which intracellular huge vacuoles continuous
      to the cell exterior were formed as the result of multiple granule-to-granule
      fusion as well as granule-to-plasma membrane fusion. The other type was local
      exocytotic release of a single or a few secretory granules near the plasma
      membrane. The multigranular exocytosis was restricted to type 4 and 5 secretory
      cells while single or a few granular exocytosis was seen in type 1, 2, 4 and 5
      secretory cells. This may be because secretory granules are larger and more
      closely packed in type 4 and 5 secretory cells than in other types of secretory
      cells. Type 3 secretory cells contained abundant cytoplasmic filaments, and
      showed no exocytotic feature, suggesting transitional cells between secretory
      cells and ciliated cells.

PMID- 9602530
TI  - A novel muscle spindle containing muscle fibres devoid of sensory innervation in
      the posterior cricoarytenoid muscle of the normal adult guinea pig.
AB  - A novel muscle spindle composed of five thin intrafusal muscle fibres and four
      thick muscle fibres was encountered in the posterior cricoarytenoid muscle of the
      normal adult guinea pig. Four intrafusal muscle fibres of the five were
      innervated by the annulospiral type of sensory ending, but lacked a distinct
      aggregation of equatorial nuclei such as bags and chains. On the other hand, one
      intrafusal fibre and four thick fibres between the layers of the spindle capsule
      absolutely lacked sensory innervation and were almost similar in the fine
      structural features to neighbouring extrafusal fibres. These fibres are
      considered to fail to receive the sensory innervation in an early stage of
      development, and to retain an undifferentiated feature of intrafusal fibre in the
      intracapsular space into adulthood or to follow the course of extrafusal
      differentiation between the layers of the spindle capsule. It is suggested
      therefore that this muscle spindle may be primitive.

PMID- 9602531
TI  - Immunolocalization of fibronectin and its receptors integrin alpha 3 and alpha 5
      subunits in the rat limb development.
AB  - In the rat hind limb bud aged between prenatal days 14 and 16, immunoreactions of
      fibronectin in the apical ectodermal ridge were localized on the plasma membranes
      of epidermal cells and cytoplasmic projections of the underlying mesenchymal
      cells, which are in contact with the basal lamina. Those of integrin alpha 3 and
      alpha 5 subunits also appeared on such areas. Definite immunoreactions of
      fibronectin and both integrin subunits were seen in cell to cell contact areas of
      mesenchymal cells which are associated with the marginal vein, or with each other
      forming solid cell cords, and appeared on the basal plasma membrane of
      endothelial cells of the growing capillaries arising from the marginal vein.
      These findings suggest that fibronectin may work as a ligand for alpha 3 beta 1
      and/or alpha 5 beta 1 integrins expressed by the mesenchymal and vasoformative
      cells in developing limb bud.

PMID- 9602532
TI  - Purification and some properties of IMP dehydrogenase of Bacillus cereus.
AB  - IMP dehydrogenase was purified from a crude extract of B, cereus cells. The
      molecular mass of the purified enzyme was estimated to be 56 kDa by SDS-PAGE and
      225 kDa by gel filtration. The optimum pH of the enzyme was about 9.5. The first
      seven residues at N-terminus of the enzyme was determined to be Met-Trp-Glu-Ser
      Lys-Phe-Val. The enzyme showed a significant specificity for inosine nucleotides
      among 15 purines and pyrimidines tested, but not acted on other purines and
      pyrimidines including inosine. Among 11 metal ions and 3 enzyme inhibitors
      tested, Al3+ activated the IMP dehydrogenase. The enzyme activity was strongly
      inhibited by Zn2+ and Fe3+.

PMID- 9602533
TI  - Release of spirosin associated with potassium phosphate-induced autolysis in
      Lactobacillus reuteri DSM 20016.
AB  - We have studied the effect of medium components on spirosin production in
      Lactobacillus reuteri DSM 20016 to get some insight into the function of
      spirosome in Lactobacillus. Among those investigated, only potassium phosphate
      was found to influence the production of spirosin. Though it was not effective at
      concentrations lower than 0.6%, it promoted the spirosin production and its
      accumulation into culture medium in particular, at higher concentrations. The
      accumulation has been demonstrated to originate inthe release of spirosin due to
      the bacterial autolysis induced by the higher concentrations of potassium
      phosphate, The autolytic effect of potassium phosphate was assumed to be a
      concerted action by phosphate and potassium ions at the concentrations higher
      than 0.1 and 0.4 M, respectively. A possible role of spirosin as a sensor protein
      of bacterial two-component regulatory system was discussed.

PMID- 9602535
TI  - Base-compositional biases and the bat problem. III. The questions of
      microchiropteran monophyly.
AB  - Using single-copy DNA hybridization, we carried out a whole genome study of 16
      bats (from ten families) and five outgroups (two primates and one each
      dermopteran, scandentian, and marsupial). Three of the bat species represented as
      many families of Rhinolophoidea, and these always associated with the two
      representatives of Pteropodidae. All other microchiropterans, however, formed a
      monophyletic unit displaying interrelationships largely in accord with current
      opinion. Thus noctilionoids comprised one clade, while vespertilionids,
      emballonurids, and molossids comprised three others, successively more closely
      related in that sequence. The unexpected position of rhinolophoids may be due
      either to the high AT bias they share with pteropodids, or it may be
      phylogenetically authentic. Reanalysis of the data with varying combinations of
      the five outgroups does not indicate a rooting problem, and the inclusion of many
      bat lineages divided at varying levels similarly discounts long branch attraction
      as an explanation for the pteropodid-rhinolophoid association. If rhinolophoids
      are indeed specially related to pteropodids, many synapomorphies of
      Microchiroptera are called into question, not least the unitary evolution of
      echolocation (although this feature may simply have been lost in pteropodids).
      Further, a rhinolophoid-pteropodid relationship--if true--has serious
      implications for the classification of bats. Finally, among the outgroups, an
      apparent sister-group relation of Dermoptera and Primates suggests that flying
      lemurs do not represent the ancestors of some or all bats; yet, insofar as
      gliding of the type implemented in dermopterans is an appropriate model for the
      evolution of powered mammalian flying, the position of Cynocephalus in our tree
      indirectly strengthens the argument that true flight could have evolved more than
      once among bats.

PMID- 9602534
TI  - The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine: its role
      in cell growth and disease.
AB  - The reversible phosphorylation of tyrosines in proteins plays a key role in
      regulating many different processes in eukaryotic organisms, such as growth
      control, cell cycle control, differentiation cell shape and movement, gene
      transcription, synaptic transmission, and insulin action. Phosphorylation of
      proteins is brought about by enzymes called protein-tyrosine kinases that add
      phosphate to specific tyrosines in target proteins; phosphate is removed from
      phosphorylated tyrosines by enzymes called protein-tyrosine phosphatases.
      Phosphorylated tyrosines are recognized by specialized binding domains on other
      proteins, and such interactions are used to initiate intracellular signaling
      pathways. Currently, more than 95 protein-tyrosine kinases and more than 55
      protein-tyrosine phosphatase genes are known in Homo sapiens. Aberrant tyrosine
      phosphorylation is a hallmark of many types of cancer and other human diseases.
      Drugs are being developed that antagonize the responsible protein-tyrosine
      kinases and phosphatases in order to combat these diseases.

PMID- 9602536
TI  - Knowledge acquired and decisions made: triadic interactions during allogrooming
      in wild bonnet macaques, Macaca radiata.
AB  - The pressures of developing and maintaining intricate social relationships may
      have led to the evolution of enhanced cognitive abilities in many nonhuman
      primates. Knowledge of the dominance ranks and social relationships of other
      individuals, in particular, is important in evaluating one's position in the rank
      hierarchy and affiliative networks. Triadic interactions offer an excellent
      opportunity to examine whether decisions are taken by individuals on the basis of
      such knowledge. Allogrooming supplants among wild female bonnet macaques (macaca
      radiata) usually involved the subordinate female of a grooming dyad retreating at
      the approach of a female dominant to both members of the dyad. In a few
      exceptional cases, however, the dominant member of the dyad retreated; simple non
      cognitive hypotheses involving dyadic rank differences and agonistic
      relationships failed to explain this phenomenon. Instead, retreat by the dominant
      individual was positively correlated with the social attractiveness of her
      subordinate companion (as measured by the duration of grooming received by the
      latter from other females in the troop). This suggests that not only does an
      individual evaluate relationships among other females, but does so on the basis
      of the amount of grooming received by them. Similarly, the frequency of
      approaches received by any female was correlated with her social attractiveness
      when she was the dominant member of the dyad, but not when she was the
      subordinate. This indicated that approaching females might be aware of the
      relative dominance ranks of the two allogrooming individuals. In logistic
      regression analyses, the probability of any individual retreating was found to be
      influenced more by her knowledge of her rank difference with both the other
      interactants, rather than by their absolute ranks. Moreover, information about
      social attractiveness appeared to be used in terms of correlated dominance ranks.
      The nature of knowledge acquired by bonnet macaque females may thus be
      egotistical in that other individuals are evaluated relative to oneself,
      integrative in that information about all other interactants is used
      simultaneously, and hierarchical in the ability to preferentially use certain
      categories of knowledge for the storage of related information from other
      domains.

PMID- 9602537
TI  - Revised karyotype of Alouatta caraya (Primates: Platyrrhini) based on
      synaptonemal complex and banding analyses.
AB  - Most primates studied have the usual XX/XY sex-chromosome system. However,
      exceptions to this rule among howler monkeys have been suggested by several
      authors. Recently a quadrivalent was discovered in male meiosis of Alouatta
      caraya and it was established that this species has an X1X2Y1Y2 sex chromosome
      system. On that basis, a cytogenetic analysis of 25 males of this species is
      described, showing the corrected karyotype of this species. Each chromosome
      involved in the particular sex-chromosome system of this species is identified on
      the basis of mitotic chromosome measurements, G and C-banding patterns as well as
      on the relative measurements of synaptonemal complexes. It is now established
      that A. caraya has a karyotype with 2n = 52 in both sexes, and that the male one
      shows a single autosome #7 (X2) besides the X (X1) and the two products of the
      reciprocal translocation between the second autosome #7 and the Y chromosome (Y1
      and Y2), while females show a homomorphic pair #7 (X2) and a pair of X1. The
      evolutionary implications of the exceptional primate species having composite sex
      chromosome systems are discussed.

PMID- 9602538
TI  - Mink 5S rRNA genes map to 2q in three loci suggesting conservation of synteny
      with human 1q.
AB  - By in situ hybridization we show that the SS rRNA genes in the mink map to
      chromosome 2q in three loci. The 2q1.1 locus containing 34% of the 5S rDNA, maps
      close to the centromere, and the remaining two loci of the 5S rDNA map to 2q1.3
      (52%) and to 2q2.3. (14%). These data were obtained with a tritiated transcript
      of the 5S rRNA gene containing 121 bp. In a comparative FISH study performed with
      a biotinylated transcript of the 5S rRNA gene the procedure failed to detect the
      2q2.3 site. A closely corresponding difference between the two procedures
      experienced previously in man and in the crab-eating macaque is discussed. The
      present results suggest a homology between 2q in the mink and part of 1q in man
      harbouring the 5S rRNA genes in 1q42.13 and 1q31, respectively.

PMID- 9602539
TI  - Variation and heritability of aristal morphology in a natural population of
      Drosophila mediopunctata.
AB  - We studied the major sources influencing the variation of the number of aristal
      branches in a natural population of Drosophila mediopunctata. Flies were
      collected on six occasions at different altitudes in Parque Nacional do Itatiaia
      (Brazil). The progenies of these flies were reared in the laboratory at 16.5
      degrees C. The number of aristal branches ranges from 11 to 15 and is influenced
      by sex. Estimates of the natural heritability showed that at least 20% of the
      total phenotypic variation is due to additive genetic variation. Although the
      heritability of this trait estimate in the laboratory was larger (42%), the
      difference between the two estimates is not statistically significant. Thus, for
      the number of aristal branches, laboratory estimates of heritability provide
      reasonable estimations of both the magnitude and significance of heritabilities
      in nature. The mean numbers of aristal branches in the wild-caught flies from
      different altitudes or months are homogeneous. The same was observed for the
      means of its progeny kept in the laboratory under controlled conditions. On the
      other hand, wild-caught females have significantly fewer aristal branches than
      their laboratory-raised daughters, which suggests that an environmental factor or
      factors may have an important influence on this trait.

PMID- 9602540
TI  - Mapping of the porcine erythropoietin gene to chromosome 3p16-p15 and ordering of
      four related subclones by fiber-FISH and DNA-combing.

PMID- 9602541
TI  - Lack of pairing loop formation in synaptonemal complex preparation of a boar
      carrying an inversion.

PMID- 9602542
TI  - Delta duplications enhance negative complementation of some Abruptex alleles in
      Drosophila melanogaster.

PMID- 9602543
TI  - Circulatory response to hyperthermia during acute normovolaemic haemodilution.
AB  - Cats anaesthetized with a mixture of chloralose and urethane were exposed to heat
      stress in two groups. In the first group (n = 10) of control animals, the effect
      of heat stress on haemodynamic variables was recorded at control haematocrit
      (HCT) of 42.0 +/- 1.0%. In a second group, the effect of heat stress was studied
      after induction of acute normovolaemic haemodilution (HCT of 13.0 +/- 1.0%).
      Haemodilution was induced to a maximum of 60% replacement of blood with dextran
      (mol.wt. 150,000). Heat stress was induced by surface heating and core body
      temperature was raised from 37 degrees C to 42 degrees C. The effect of heat
      stress and haemodilution on various haemodynamic variables, viz. left ventricular
      pressure (LVP), left ventricular contractility (LVdP/dtmax), heart rate (HR),
      cardiac output (CO), arterial blood pressure (ABP), right atrial pressure (RAP),
      and arterial blood PO2, PCO2 and pH was examined. Haemodilution produced
      significant (P < 0.05) increases in HR and CO but there were no significant (P >
      0.05) changes in ABP, RAP, LVdP/dtmax and total peripherial resistance (TPR).
      Hyperthermia caused a significant fall (P < 0.05) in TPR. However, the percentage
      fall in TPR was higher in the control group. On exposure to heat stress, there
      were significant (P < 0.05I increases in HR and CO in both the groups; however,
      HR and CO values were significantly (P < 0.05) higher in the haemodiluted group
      compared to the control. The latter findings could be due either to the higher
      basal values of these variables with the fall in HCT or to inefficient
      cardiovascular regulatory mechanisms. The lack of efficient regulatory control
      under such severe stress conditions makes the cardiovascular system of anaemic
      animals more vulnerable to heat stress. In conclusion, the results of the present
      study showed deleterious effects of heat stress in both the groups. The higher
      values of HR and CO in the haemodiluted group may be responsible for circulatory
      failure at low HCT values, indicating a higher risk in the haemodiluted group as
      compared to the control group.

PMID- 9602544
TI  - A model of evaporation from the skin while wearing protective clothing.
AB  - A simple model was developed to describe the transport of water vapour from
      subjects working in hot environments while wearing chemical-protective clothing.
      The goal of the modelling was to obtain a better estimate of evaporative cooling
      of the subjects, as it was hypothesised that calculations of evaporative heat
      loss based on changes in dressed weight over-estimate the actual benefit
      experienced by the subjects. The model employed measured values of vapour
      pressure within the clothing ensemble to estimate the skin vapours pressure. The
      resistance of the clothing ensemble to water vapour transport was calculated from
      measurements of the physical properties of the materials in conjunction with
      estimates of the resistance of air layers between the clothing layers. The model
      predicts mean evaporation rates from the skin that are approximately 60% of those
      calculated from measured changes in dressed weight. Error analysis failed to
      account for the magnitude of this difference and possible explanations for the
      difference are advanced. A brief examination of the effect of wicking suggests
      that some of the difference results from a reduction of the resistance of the
      garment to water vapour due to wicking of liquid sweat through fabric layers.

PMID- 9602545
TI  - The non-junctional sarcolemmal cytoskeleton: the costameres.
AB  - In skeletal muscle fibers the costameres have been defined by Pardo et al. (1983)
      as transverse circumferential elements of the cytoskeleton associated to the
      sarcolemma. Since the first immunolocalization, carried out with purified
      antivinculin antibodies to the present day, about 10 proteins have been located
      in costameres, as well as some transmembrane proteins of the integrin
      superfamily. In particular the colocalization of vinculin and talin and the
      presence of the integrins confers to this system the description of the adherens
      junctions type cell-ECM, while the presence of dystrophin in correspondence to
      both A and I bands with Z line negative is important for the stabilization of the
      membrane of the skeletal muscle fiber. We are therefore of the opinion that
      costameres can be defined as a real proteic "machinery".

PMID- 9602546
TI  - Measurement reliability of dynamic x-rays of the cervical spine: an experimental
      model.
AB  - A blind test of measurement reliability was performed in vitro using lateral x
      rays of cervical vertebrae. Dry specimens of C3 and C4 were mounted in a movable
      frame and flexion/extension was simulated. Lateral x-rays were taken for each
      degree from 15 degrees flexion to 15 degrees extension. Then the x-rays were
      measured by four raters. The results show a high level of absolute measurement
      error. This suggests caution in accepting existing literature data on cervical x
      ray measurements unless some indicator of the personal measuring accuracy of the
      rater is specified. The procedure described in this paper can be used to
      ascertain such accuracy.

PMID- 9602547
TI  - Post-natal bone growth in the semicircular canals of the dog.
AB  - Dogs from the same litter, divided into three groups aged 10, 25, and 50 days,
      received an intraperitoneal injection of tetracycline for two successive days.
      The temporal bones were fixed, embedded in methylmethacrylate, sectioned in to a
      single 100 microns thick section along the main axis of the anterior and lateral
      semicircular canals, grounded by hand to 30 microns and observed at UV light. The
      new bone tissue is laid down both at the endosteal and endochondral bone of the
      anterior and lateral semicircular canals. The bone deposition decreases with the
      age of the animal and earlier at the endosteum than at the endochondral bone.

PMID- 9602548
TI  - Neurochemical features of feline superior mesenteric ganglion.
AB  - The distribution of various neuronal peptides: substances P (SP), somatostatin
      (SOM), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and
      vasoactive intestinal polypeptide (VIP) was studied by means of
      immunofluorescence in the superior mesenteric ganglion of the cat. Several
      populations of neurons can be characterized by their contents of
      neurotransmitters. All of the neuropeptides were seen in the ganglion cells in
      different proportions but the majority of the cells were NPY-immunopositive and
      immunoreactivity for CGRP, SOM and SP was restricted to rather small
      subpopulations. Only a few ganglionic cells were VIP-immunoreactive. The neuronal
      fibres expressed different peptide immunoreactivity as well; the most widespread
      ones were VIP-containing fibres. The neuronal filaments immunoreactive to the
      rest of neuropeptides were seen more rarely, usually surrounding immunonegative
      cell bodies and blood vessels.

PMID- 9602549
TI  - Denervation muscular atrophy. Studies on the soleus muscle of the albino rat (LM,
      TEM, immunofluorescence, image analysis).
AB  - In previous researches the Authors hypothesized that the loss of cytoskeletal
      proteins such as desmin and vinculin lead to degenerative ultrastructural changes
      which occur in muscular disuse atrophy. In order to support this hypothesis they
      carried out a morphometric, structural, ultrastructural and immunofluorescence
      study on the soleus muscle of albino rats after resection of the ischiatic nerve.
      It was demonstrated that a chronological sequence of the damage took place in
      particular three levels of damage. The last level of damage proved to be
      irreversible; the first level assured complete recovery in the case of rapid
      reinnervation, whereas the possible reversibility of the second level remained
      open to question. The disappearance of vinculin and desmin was observed in a
      period between 72 hours and 7 days, i.e. before the appearance of ultrastructural
      damage. On this ground the Authors explained the correlation between the loss of
      the proteins and degenerative changes. In conclusion the Authors correlated the
      gene expression of cytoskeletal and contractile proteins with the neuropeptides
      released by motor axon.

PMID- 9602550
TI  - Inter-laboratory comparison of air particulate monitoring data.
AB  - This paper compares three analytical methods that are often used to analyze
      composition of atmospheric aerosol: Ion Chromatography (IC), Proton Induced X-ray
      Emission (PIXE), and X-ray Fluorescence (XRF). Three monitoring studies are
      discussed: (1) a comparison of air particulate data collected by several
      independent sampler/analytical technique suites run by different laboratories;
      (2) a study involving two identical samplers and a single suite of analytical
      techniques; and (3) analysis of identical aerosol samples by two different
      techniques (XRF vs. PIXE). While the XRF versus PIXE project shows a very good
      agreement for most elements, the first interlaboratory study demonstrates the
      "real-life" noise introduced into the final data set by various sampling
      complications and different collection characteristics of the samplers used. The
      XRF versus PIXE study also revealed an unexplained deviation in measured sulphur
      concentrations for very lightly loaded samples. In the five-sampler comparison,
      two data sets provided by IC were approximately 20% lower than the three data
      sets obtained by PIXE and XRF. When two identical IMPROVE-compatible samplers
      were used and samples were subjected to similar procedures and the same
      analytical techniques, the variability between the two air concentration data
      sets significantly decreased.

PMID- 9602551
TI  - Particulate emission rates for unpaved shoulders along a paved road.
AB  - This paper reports the first empirical estimate of particle emissions from
      unpaved shoulders along paved roads. Its objectives are to develop and
      demonstrate an emission rate measurement methodology that can be applied in
      different areas; identify the mechanisms that suspend dust from unpaved shoulders
      and the observables related to this suspension process; and quantify PM10 mass
      emissions in the form of an emission rate. To achieve these objectives, fast
      response observations from nephelometers and a sonic anemometer were used to
      characterize short-lived dust plumes generated by passing vehicles. In addition,
      detailed soil surface measurements determined the mechanical properties of the
      shoulder surfaces. Large traffic-induced turbulence events that led to
      significant dust entrainment were almost exclusively caused by "large" vehicles
      such as trucks, semis, and vehicles pulling trailers, all traveling 50-65 mph.
      PM10 emission rates for these large, fast-traveling vehicles were determined to
      be 8 +/- 4 grams per vehicle kilometer traveled under dry conditions. Emissions
      due to smaller vehicles such as cars, vans, and sport utility vehicles were
      negligible for normal on-road driving. These results indicate that the majority
      of PM10 emissions from unpaved shoulders is caused by relatively few vehicles.

PMID- 9602552
TI  - Temporal and spatial distributions of ozone in Atlanta: regulatory and
      epidemiologic implications.
AB  - Relationships between ambient levels of selected air pollutants and pediatric
      asthma exacerbation in Atlanta were studied retrospectively. As a part of this
      study, temporal and spatial distributions of ambient ozone concentrations in the
      20-county. Atlanta metropolitan area during the summers of 1993, 1994, and 1995
      were assessed. A universal kriging procedure was used for spatial interpolation
      of aerometric monitoring station data. In this paper, the temporal and spatial
      distributions of ozone are described, and regulatory and epidemiologic
      implications are discussed. For the study period, the Atlanta ozone nonattainment
      area based on the 1-h, exceedance-based standard of 0.12 ppm is estimated to
      expand--from 56% of the Atlanta MSA by area and 71% by population to 88% by area
      and 96% by population--under the new 8-h, concentration-based standard of 0.08
      ppm. Regarding asthma exacerbation, a 4% increase in pediatric asthma rate per 20
      ppb increase in ambient ozone concentration was observed (p-value = 0.001), with
      ambient ozone level representing a general indicator of air quality due to its
      correlations with other pollutants. The use of spatial ozone estimates in the
      epidemiologic analysis demonstrates the need for control of demographic
      covariates in spatiotemporal assessments of associations of ambient air pollutant
      concentrations with health outcome.

PMID- 9602553
TI  - Total volatile organic compounds in the urban environment of Delhi.
AB  - Total volatile organic compounds (TVOCs) in the urban ambient environment of
      Delhi were monitored from November 1994 to June 1995 at 13 sites using an
      inexpensive and a manual-labor-intensive sample collection procedure in want of
      sophisticated equipment. The results of the study show appreciable levels of
      TVOCs in the ambient environment of Delhi. The amount of TVOCs in the ambient
      environment was found to vary between 3 and 42 ppmv and exhibited wide temporal
      and seasonal variations. On a diurnal cycle, TVOC levels mostly peaked at 9:00
      a.m., which coincided with the peak traffic hour. TVOC buildup in the urban
      atmosphere has serious implications for air quality through the formation of
      highly toxic oxidants. The results of this preliminary study make out a strong
      case for a regular monitoring of TVOCs in the urban environment of Delhi.

PMID- 9602554
TI  - Carbon monoxide trend, meteorology, and three-way catalysts in Mexico City.
AB  - From the analysis of data of the Inspection/Maintenance (I/M) program, and of the
      long-term trend of ambient CO concentrations in Mexico City, it is inferred that
      three-way catalysts (TWCs) have a 45% efficiency, well below the expected 90%
      value. The most probable causes are sulfur poisoning, lead contamination, and
      ceramic breakage due to bumps and potholes on the streets. Also, we have found a
      ratio between the average daily peak value of atmospheric CO and gasoline
      consumption: (11 +/- 1) ppbCO/MLm (million liters of gasoline per month) in 1988
      decaying to (10 +/- 1) in 1991 for Mexico City before the introduction of TWCs.
      In addition, we found a correlation between the monthly averages of CO daily peak
      and meteorological variables, explaining most of the seasonal changes using only
      the intensity of the inversion layer and surface wind speed.

PMID- 9602555
TI  - Child abuse and neglect: usefulness of the animal data.
AB  - This article reviews and critically discusses the relevance of animal data to
      research on child abuse and neglect. Although parental investment theory can be
      useful in investigating the adaptiveness, if any, of child abuse and neglect, the
      evolutionary approach also has some limitations. The most suitable animal models
      for investigating the psychosocial processes underlying child abuse and neglect
      are probably found among the nonhuman primates. Whereas the heuristic value of
      social deprivation paradigms may be limited, recent studies suggest that the
      spontaneous occurrence of infant maltreatment in monkeys may be the closest
      approximation to child maltreatment provided by nonhuman animals. The
      investigation of adaptive and maladaptive processes in the parenting behavior of
      socially living nonhuman primates can inform research on child abuse and neglect
      and allow investigators to conduct studies that would be difficult or impossible
      in humans.

PMID- 9602556
TI  - Child abuse and neglect--usefulness of the animal data: comment on Maestripieri
      and Carroll (1998)
AB  - Issues related to definition, epidemiology, and etiology in the human literature
      are examined to explore possible contributions that D. Maestripieri and K. A.
      Carroll's (1998) discussion of nonhuman primate research can make to an
      understanding of child maltreatment. Similarities and differences between
      maltreatment in nonhuman primates and humans are discussed, and recommendations
      are proffered that could be useful in advancing research on child abuse and
      neglect in both monkeys and humans.

PMID- 9602557
TI  - Words, deeds, and motivations: comment on Maestripieri and Carroll (1998)
AB  - A considerable proportion of Old World monkey mothers living in social groups
      under seemingly benign conditions maltreat their young. This interesting finding
      is the basis for the suggestion by D. Maestripieri and K. A. Carroll (1998) that
      monkeys might provide an animal model for investigating child abuse and neglect
      in the human population. This suggestion tacitly assumes that the phenomena of
      abuse and neglect in monkeys and humans are based on similar processes. This
      possibility is more plausible for neglect than for abuse. Child abuse shows such
      great diversity of forms and causes in human societies that it is unlikely to
      have a natural counterpart among nonhuman primates. The suggestion that it does
      may inadvertently lend support to attitudes that are unduly restrictive or
      actively opposed to animal research in psychology.

PMID- 9602558
TI  - Infant abuse and neglect in monkeys--a discussion of definitions, epidemiology,
      etiology, and implications for child maltreatment: reply to Cicchetti (1998) and
      Mason (1998)
AB  - In response to D. Cicchetti's (1998) and W. A. Mason's (1998) commentaries, this
      article scrutinizes infant maltreatment in monkeys and its public health
      implications. Studies of infant abuse and neglect in monkeys have used
      operational definitions based on (a) adult behavior or (b) adult behavior and
      infant outcome (depending on data available for analysis). Direct comparisons
      between the incidence of maltreatment in monkey and human populations can be only
      tentative as a result of differences in operational definitions of maltreatment.
      A simplified version of the ecological-transactional model of maltreatment can be
      used in research with nonhuman primates, and different species can be used to
      model different aspects of the human phenomenon. Although abuse and neglect take
      different forms in animals and humans, research with animal models can make an
      important contribution to elucidating the adaptive function, if any, of child
      maltreatment and the proximate mechanisms underlying its occurrence.

PMID- 9602559
TI  - Gender differences in the diagnosis of mental disorders: conclusions and
      controversies of the DSM-IV.
AB  - One of the more controversial issues in terms of mental disorder diagnoses has
      been their differential sex prevalence. The conclusions provided in the 4th
      edition of the American Psychiatric Association's (1994) Diagnostic and
      Statistical Manual of Mental Disorders were derived from systematic reviews of
      the research literature. However, this research is perhaps complicated by common
      sources of error. Two sources, in particular, are emphasized here: biases in
      sampling and biases within the diagnostic criteria themselves. The potential for
      such biases is illustrated for a wide variety of mental disorder diagnoses, and
      suggestions for research to address them are provided.

PMID- 9602560
TI  - Preventing breast cancer with tamoxifen.

PMID- 9602561
TI  - False positives on mammograms.

PMID- 9602562
TI  - New ratings for infertility clinics.

PMID- 9602563
TI  - Preempting surgical pain.

PMID- 9602564
TI  - Link between blood clots and cancer.

PMID- 9602565
TI  - Caution with fluoride-containing cleaners.

PMID- 9602566
TI  - A new substitute for sugar.

PMID- 9602567
TI  - Treatment for hair pulling disorder.

PMID- 9602568
TI  - Triglycerides and heart disease.

PMID- 9602569
TI  - Cigarette cover-up.

PMID- 9602570
TI  - New B vitamin recommendations.

PMID- 9602571
TI  - Spouses can help bipolar patients.

PMID- 9602572
TI  - Death in the dental chair: an avoidable catastrophe?

PMID- 9602573
TI  - Conscious awareness during general anaesthesia: patients' perceptions, emotions,
      cognition and reactions.
AB  - We interviewed 45 patients, who answered advertisements (n = 21) or were referred
      by colleagues (n = 24), about their experience of intraoperative awareness using
      a standardized questionnaire. Auditory perceptions, hearing sounds or voices were
      mentioned by all patients (45 of 45): 33 of 45 patients understood and recalled
      conversations; 21 of 45 patients had visual perceptions; 12 of 21 recognized
      things or faces; 29 of 45 patients felt being touched; three patients had the
      sensation of moderate pain; and eight patients were in severe pain. Patients'
      feelings were mostly related to paralysis (27 of 45), helplessness (28 of 45),
      anxiety and fear (22 of 45); 18 were in severe panic. All patients (45 of 45)
      recognized the situation as a real event: 22 of 45 patients experienced
      unpleasant after effects; 11 suffered from anxiety and nightmares; and three
      developed post-traumatic stress disorder syndrome and required medical treatment.
      Twenty of 45 patients were especially attentive to emotionally relevant remarks
      on their own person, their disease and the course of their operation. The
      accuracy of sensory perception indicates a very high level of cognitive
      performance of patients during intraoperative awareness.

PMID- 9602574
TI  - Preoperative assessment for difficult intubation in general and ENT surgery:
      predictive value of a clinical multivariate risk index.
AB  - Several clinical multifactorial indexes have been described for predicting
      difficult laryngoscopy or intubation, or both, mostly in general surgery, and
      less frequently in ENT surgery. The objective of this study was to develop and
      validate a single clinical index for prediction of difficulty in tracheal
      intubation in both ENT and general surgery. We studied a population of 1200
      consecutive ENT and general surgical patients. Clinical criteria were tested
      using univariate and multivariate analysis. Difficult intubation was defined as
      requiring unusual techniques. Logistic regression identified seven criteria as
      independent predictors of difficult tracheal intubation; previous history of
      difficult intubation; pathologies associated with difficult intubation; clinical
      symptoms of pathological airway; inter-incisor gap and mandible luxation;
      thyromental distance; head and neck movement; and Mallampati's modified test.
      Point values were assigned to each of these factors in proportion to regression
      coefficients representing the relative weight of each predictive intubation
      difficulty factor, the sum comprising the score. The best predictive threshold
      was chosen using a receiver operating characteristic curve. We then prospectively
      studied and validated the score in a population of 1090 consecutive ENT and
      general surgery patients. The sensitivity and specificity of the predictions were
      94% and 96% in general surgery, 90% and 93% in non-cancer ENT surgery, and 92%
      and 66% in ENT cancer surgery, respectively.

PMID- 9602575
TI  - Pre-emptive effect of multimodal analgesia in thoracic surgery.
AB  - Thirty subjects undergoing posterolateral thoracotomy were allocated randomly to
      receive one of two analgesic regimens: group Pre received i.v. morphine, i.m.
      diclofenac and intercostal nerve blocks from T2 to T11, 20 min before operation
      and placebo injections after operation. Group Post received placebo injections
      before operation, and i.v. morphine, i.m. diclofenac and intercostal nerve blocks
      from T2 to T11 at the end of surgery, before discontinuation of anaesthesia.
      Visual analogue pain scores, extent and duration of intercostal nerve block,
      analgesic consumption and complications were assessed during the postoperative
      period by a single blinded observer. Subjects were followed-up for a minimum of
      12 months to determine the incidence of post-thoracotomy pain syndrome. During
      the first 48 h after operation there were lower pain scores in group Pre when
      taking a vital capacity breath but there were no significant differences between
      the groups in any other measure. The effects of pre-emptive analgesia given
      before surgery appeared to be relatively modest in terms of analgesia, analgesic
      consumption and long-term outcome and were of limited clinical significance.

PMID- 9602576
TI  - Combining propofol with morphine in patient-controlled analgesia to prevent
      postoperative nausea and vomiting.
AB  - We have studied the antiemetic effects of propofol when mixed with morphine in a
      patient-controlled analgesia (PCA) pump after major gynaecological surgery. In a
      double-blind, randomized, controlled study, 50 women, ASA I or II, received a
      standardized anaesthetic comprising thiopental, morphine, atracurium, nitrous
      oxide and oxygen with enflurane, and received postoperative PCA with morphine
      mixed with either 1% propofol or lvelip. The PCA bolus was morphine 1 mg with
      propofol 5 mg or lvelip 0.5 ml, with a lockout time of 5 min. Postoperative
      nausea and vomiting (PONV) were assessed by the nursing staff using a four-point
      ordinal scale and by the patient using a visual analogue scale for 48 h after
      surgery. The two groups were similar in the potential factors influencing the
      incidence of PONV. There were no significant differences between the two groups
      in any of the study measurements of PONV. There were, no side effects after
      propofol. Propofol, when mixed with morphine in this dose combination for PCA,
      did not decrease the incidence of nausea and vomiting in women undergoing major
      gynaecological surgery.

PMID- 9602577
TI  - Prophylaxis for vomiting by children after tonsillectomy: ondansetron compared
      with perphenazine.
AB  - We have compared the effects of ondansetron and perphenazine on vomiting after
      tonsillectomy in 216 healthy children, aged 2-12 yr. The study was randomized,
      stratified, blocked and double blind. Anaesthesia was induced with propofol i.v.
      or by inhalation of halothane and nitrous oxide. Ondansetron 150 micrograms kg-1
      or perphenazine 70 micrograms kg-1 was administered i.v. after induction of
      anaesthesia in a double-blind manner. Perioperative management of emesis, pain,
      fluids and patients discharge were standardized. Ondansetron and perphenazine had
      similar effects on postoperative vomiting (44% vs 41%; ondansetron vs
      perphenazine P = 0.77). By logistic regression analysis, the only significant
      predictor of postoperative vomiting was sex, that is males had a greater
      incidence of vomiting (49% vs 35%; P = 0.016). In-hospital vomiting was
      associated with a prolongation of stay in the day-care surgical unit of 7 min per
      episode of vomiting (P = 0.015). We conclude that ondansetron and perphenazine
      had similar effects on vomiting in children after tonsillectomy in a day-case
      setting.

PMID- 9602578
TI  - Effects of preinduction and intraoperative warming during major laparotomy.
AB  - We have investigated the influence of active warming before and during operation
      on blood loss, transfusion requirements, duration of stay in the post-anaesthesia
      care unit (PACU) and perioperative costs in 40 patients undergoing major
      abdominal surgery. Patients were allocated randomly to one of two groups: in the
      study group (n = 20), patients were actively warmed using forced air for 30 min
      before induction of general anaesthesia and during anaesthesia. Passive
      protection against heat loss consisted of circulating water mattresses, blankets
      and fluid warming devices, and was used both in the active warming group and in
      the control group (n = 20). At the end of surgery the change in core temperature
      was significantly less in the group of actively warmed patients (0.5 (SD 0.8)
      degree C vs 1.5 (0.8) degree C; P < or = 0.01). Blood loss and transfusion
      requirements were less in the actively warmed patients, who had a shorter
      duration of stay in the PACU (94 (SD 42) min vs 217 (169) min; P < or = 0.01) and
      a 24% reduction in total anaesthetic costs.

PMID- 9602579
TI  - Relationship between cardioventilatory coupling and respiratory sinus arrhythmia.
AB  - Recent studies have suggested a role for respiratory sinus arrhythmia in
      improving pulmonary gas transfer. However, the physiological role of
      cardioventilatory coupling is unknown. We have tested the hypothesis that
      cardioventilatory coupling aligns heart beats at positions of the ventilatory
      cycle where they are maximally affected by respiratory sinus arrhythmia (RSA). In
      15 anaesthetized, spontaneously breathing subjects, we recorded continuously the
      timing of inspiration and the ECG. We then plotted the change in RR interval
      which occurred, as a result of RSA, after onset of inspiration (RSA plot). By
      comparing these RSA plots with the distribution of heart beats during the
      ventilatory cycle, we were able to examine the positioning of heart beats
      relative to acceleration of heart rate as a result of RSA. In all but two
      subjects we observed that during periods of strong cardioventilatory coupling,
      heart beats occurred at positions in the ventilatory cycle where they were
      maximally affected by RSA. In the presence of strong coupling, the shortest
      possible RR interval occurred during late inspiration, the longest possible RR
      interval occurred immediately before the start of inspiration. We suggest that
      cardioventilatory coupling may have a physiological role in optimizing RSA,
      perhaps to improve cardiopulmonary performance during sleep.

PMID- 9602580
TI  - Cardiovascular effects of 50% nitrous oxide in older adult patients anaesthetized
      with isoflurane or halothane.
AB  - We have studied the cardiovascular effects of equipotent concentrations of
      halothane or isoflurane, with or without 50% nitrous oxide in oxygen, in 80
      patients, aged 60 yr or more, during 20 min of stable equipotent anaesthesia. Non
      invasive measurement techniques were used, with suprasternal Doppler
      ultrasonography for estimating cardiac output. Both isoflurane and halothane
      reduced heart rate and systemic arterial pressure. With isoflurane, mean rate
      decreased from 72 (SD 9.7) to 67 (10.4) beat min-1 and with halothane from 76
      (10.1) to 65 (9.1) beat min-1 (P < 0.05). Mean diastolic arterial pressure
      decreased from 81 (11.3) to 58 (17.0) mm Hg with isoflurane and from 86 (14.7) to
      70 (13.3) mm Hg with halothane (P < 0.05). Cardiac index decreased from 3.1
      (1.03) to 2.7 (0.71) litre min-1 m-2 with isoflurane and from 3.1 (0.98) to 2.5
      (0.57) litre min-1 m-2 with halothane (P < 0.05). Systemic vascular resistance
      decreased significantly in all groups except those receiving halothane with
      nitrous oxide. Nitrous oxide resulted in significantly less depression of cardiac
      index when given with isoflurane than when given with halothane. The mean
      percentage change in cardiac index during isoflurane anaesthesia without nitrous
      oxide was 16.7%; with nitrous oxide there was a 0.5% increase. Halothane, in
      combination with nitrous oxide, resulted in greater depression of cardiac index
      than isoflurane with nitrous oxide. The mean percentage change with halothane was
      20.4% (22.2%); with isoflurane there was a 0.5% (27.1%) increase (P < 0.05).
      Hypotension was more pronounced in patients anaesthetized with isoflurane (n =
      40) than those anaesthetized with halothane (n = 40), irrespective of the
      presence of nitrous oxide. The mean percentage decrease with isoflurane was 29.7%
      (21.10%) compared with 16.8% (16.78%) with halothane (P < 0.05).

PMID- 9602582
TI  - Urinary excretion as an input variable in volume kinetic analysis of Ringer's
      solution.
AB  - The disposition of fluid given by i.v. infusion can be studied by fitting one
      volume and two-volume kinetic models to the fractioned dilution of blood
      haemoglobin and serum albumin concentrations over time. However, the two-volume
      model is sometimes associated with a high standard error in estimating the size
      of the secondary (peripheral) body fluid space, V2. To examine if a fixed
      elimination rate constant (kr) determined by urinary excretion can be used to
      make the model more stable, we infused Ringer's acetate 25 ml kg-1 over 30 min in
      15 male volunteers (mean age 35 yr). A fixed kr increased the total residual
      error when curve-fitting was applied according to the one-volume model. The two
      volume model was improved when there was a strong within-patient covariance
      between kr and V2 (r2 < or = -0.98). The size of V2 was 10 litre when the fixed
      and model-generated values of kr agreed fully.

PMID- 9602581
TI  - Influence of 0.1 minimum alveolar concentration of sevoflurane, desflurane and
      isoflurane on dynamic ventilatory response to hypercapnia in humans.
AB  - To assess the effects and site of action of a sub-anaesthetic concentration of
      isoflurane, desflurane and sevoflurane (0.1 minimum alveolar concentration (MAC))
      on respiratory control, we measured the ventilatory response to square wave
      changes in PE1CO2 against a background of normoxia. Using the computer steered
      "end-tidal forcing system", 2 min of steady state ventilation were followed by a
      step increase in PE1CO2 (1-1.5 kPa). This level was maintained for 8 min,
      followed by a step decrease to the original value for another 8 min. Each
      hypercapnic response was separated into a fast, peripheral component and a slow,
      central component, characterized by a time constant, carbon dioxide sensitivity,
      time delay and off-set. We studied 25 healthy volunteers; they performed 2-3
      studies without and 2-3 studies during inhalation of the anaesthetic agent. Level
      of sedation was scored using a subjective seven-point scale from 0 (= alert and
      awake) to 6 (unrousable). In the isoflurane (16 subjects, 33 control, 37 drug
      studies) and sevoflurane (15 subjects, 40 control, 41 drug studies) studies,
      peripheral carbon dioxide sensitivity was reduced by approximately 45% and
      approximately 27% (ANOVA, P < 0.05 vs control), respectively, without affecting
      central carbon dioxide sensitivity or apnoeic threshold. In the desflurane study
      (16 subjects, 36 control, 37 drug studies), no significant effect was observed
      for any of the variables measured. A significant relation was observed between
      sedation score and change from control in central carbon dioxide sensitivities in
      the isoflurane and desflurane studies and in the change in the ratio peripheral
      carbon dioxide sensitivity over total carbon dioxide sensitivity in the
      sevoflurane studies. At the highest level of sedation observed (score 3-arousal
      state comparable with "light sleep"--in three subjects) these latter variables
      differed significantly from those in the other observed sedation levels (scores 1
      and 2-a state of drowsiness). We conclude that 0.1 MAC of isoflurane and
      sevoflurane depressed the peripheral chemoreflex loop, without affecting the
      central chemoreflex loop. Desflurane at the same MAC showed no effect on
      peripheral and central carbon dioxide sensitivity. When the level of sedation was
      considered, our data suggested that at levels of sedation comparable with sleep,
      a depressive effect of all three anaesthetics was observed on the central
      chemoreflex loop.

PMID- 9602583
TI  - Bovine haemoglobin-based oxygen carrier for patients undergoing haemodilution
      before liver resection.
AB  - We have studied the use of ultrapurified polymerized bovine haemoglobin (HBOC
      201) in patients undergoing preoperative haemodilution before liver resection.
      After autologous blood donation of 1 litre, 12 patients (six males, six females,
      mean age 59 (35-69) yr) received Ringer's lactate solution 2 litre and, in a
      random design, 6% hydroxyethyl starch 70,000/0.5 (HES) 3 ml kg-1 or HBOC-201 0.4
      g kg-1 within 30 min. Blood samples were obtained for blood chemistry, co
      oximetry, haematology, coagulation profiles and immunology examinations before
      operation, on the day of surgery, on days 2-4 and 7 after operation, on the
      discharge day and 3 months after operation. There were no differences in patient
      characteristics, blood loss, amount of solutions infused, transfused allogeneic
      blood or duration of hospital stay. There were no local or systemic allergic
      reactions with infusion of HES or HBOC-201. Patients receiving HBOC-201 developed
      more pronounced leucocytosis and reticulocytosis during the early postoperative
      days compared with HES-treated patients. The mean maximum plasma haemoglobin
      concentration was 1.0 (SD 0.2) g dl-1 at the end of infusion of HBOC-201 was 8.5
      h. Patients in both groups experienced temporary changes in liver enzymes and
      coagulation variables which returned to normal before discharge. Urinalysis
      revealed no difference between groups and no free haemoglobin was detected in
      urine. Patients receiving HBOC-201 showed no IgE and only a slight increase in
      IgG titres to HBOC-201 on the day of discharge; these were not detectable at 3
      months. Single-dose administration of HBOC-201 was well tolerated by patients
      undergoing elective liver resection surgery and appears to be safe as a
      substitute during preoperative haemodilution.

PMID- 9602584
TI  - Blood salvage during caesarean section.
AB  - The aim of this study was to assess blood salvage during Caesarean section. In 15
      Caesarean sections, red cells lost were collected and washed with a Dideco
      machine and tested for the presence of fetoplacental material, bacterial
      contamination, free haemoglobin and fetal blood cells. Successive patients were
      allocated randomly to one of two groups. In group 1 (n = 34), intraoperative
      blood was salvaged, while group 2 served as a control. The mean amount of blood
      salvaged in group 1 was 363 (SD 153) ml. Blood was salvaged following these
      guidelines: identification of blood group of the mother and fetus; avoidance of
      aspirating blood from the umbilical cord; commencement of salvage after removing
      the fetoplacental unit; completely filling the centrifugation bowl with red
      cells; washing the cells using at least 1000 ml of physiological solution per
      bowl; and mixing the contents of the bowl, completely eliminating the buffy coat
      where fetal cells are located. In group 1, the use of homologous blood
      transfusions was significantly lower (one of 34 (2.9%) patients compared with
      eight of 34 (23.5%); P = 0.01), haemoglobin concentrations during the first 4
      days after operation were significantly higher and postoperative hospital stay
      was significantly shorter. Duration of hospital stay was significantly shorter in
      group 1 (5.3 (1.9) vs 7.3 (4) days; P = 0.003). Mean base haemoglobin
      concentrations were significantly lower in group 1 (10.7 (1.4) vs 11.7 (1.5) g dl
      1; P > 0.0001), while after surgery mean haemoglobin concentrations were
      significantly higher approximately 3 h after operation compared with the control
      group (10.2 (1.5) vs 8.6 (1.2) g dl-1; P < 0.0001). On the first day, haemoglobin
      concentrations were 9.8 (1.5) vs 8 (1.4) g dl-1 (P < 0.0001), on the second day
      9.8 (1.4) vs 7.7 (1.4) g dl-1 (P < 0.0001), on the third day 10.1 (1.5) vs 7.5
      (1.3) g dl-1 (P < 0.0001) and on the fourth day 10.4 (1.5) vs 8.1 (1.4) g dl-1 (P
      < 0.0001).

PMID- 9602585
TI  - Prevention of spinal anaesthesia-induced hypotension in the elderly: i.m.
      methoxamine or combined hetastarch and crystalloid.
AB  - We have compared two methods of reducing hypotension during spinal anaesthesia in
      elderly patients, 6% hetastarch and crystalloid or methoxamine 10 mg i.m., in
      terms of haemodynamic stability and requirements for additional vasopressors.
      Sixty-two patients (aged 60-97 yr) undergoing surgical fixation of fractured neck
      of femur were allocated randomly to receive 6% hetastarch (Hespan) 500 ml
      followed by Hartmann's solution 500 ml (group HS, n = 32) or a bolus injection of
      methoxamine 10 mg i.m. (group MX, n = 30), 10 min before induction of spinal
      anaesthesia with 0.5% hyperbaric bupivacaine 2.25-3.0 ml. Arterial pressure was
      measured non-invasively by an oscillotonometer at 2-min intervals from 0 to 40
      min and at 5-min intervals thereafter. Methoxamine 2 mg i.v. was given if
      systolic arterial pressure (SAP) decreased to < 100 mm Hg. Hypotension was
      defined as a 25% decrease from baseline SAP or mean arterial pressure (MAP).
      Patient data, sensory level and blood loss were similar in the two groups. SAP
      and MAP increased initially from baseline until induction of spinal anaesthesia
      and then decreased for 30 min in both groups, but remained higher in group MX (P
      < 0.05). Heart rate (HR) decreased from baseline in group MX (P < 0.05) and was
      less than in group HS at all times from 2 to 60 min (P < 0.01). The incidence of
      SAP hypotension (47% vs 75%; P = 0.03, odds ratio (OR) = 3.43) and MAP
      hypotension (47% vs 67%; P = 0.09, OR = 2.51) was less in group MX than in group
      HS. Requirements for rescue methoxamine i.v. (27% vs 53%, P = 0.04, OR = 3.11)
      was less in group MX than in group HS but the dose of rescue methoxamine given
      (mean 6.3 (95% confidence intervals 3.0-9.6) vs 8.9 (5.6-12.2) mg) and time to
      onset of hypotension (20.7 (14.5-26.7) vs 17.3 (11.4-23.1) min) were similar in
      groups MX and HS, respectively. We conclude that methoxamine 10 mg i.m., given 10
      min before induction of spinal anaesthesia in normovolaemic elderly patients,
      reduced subsequent SAP and MAP hypotension, HR and requirements for rescue
      vasopressor therapy compared with a combination of 6% hetastarch 500 ml and
      crystalloid 500 ml. The previously reported benefit of such volume administration
      may not extend to the elderly.

PMID- 9602586
TI  - Reduced quality of clot formation with gelatin-based plasma substitutes.
AB  - We have studied, over a wide range of dilutions using techniques of clot weight,
      thrombelastography and scanning electron microscopy, the physical properties of a
      blood clot formed in vitro when fresh blood was diluted with gelatin-based
      colloid solutions compared with crystalloid controls. The colloid solutions
      tested (3.5% polygeline (Haemaccel) and 4% succinylated gelatin (Gelofusine))
      produced clots that had reduced median weight (P < 0.001 and P = 0.018,
      respectively) and reduced mean shear modulus (P < 0.001) compared with
      crystalloid controls. Scanning electron microscopy showed that the fibrin formed
      a less extensive mesh in the presence of the gelatin-based colloids compared with
      crystalloid. Reduction in clot quality with gelatin-based colloids has not been
      noted previously and further work is needed to ascertain if this occurs in vivo
      as these solutions are used frequently in patients who require full haemostatic
      competence.

PMID- 9602587
TI  - Endocrine and metabolic effects of hypotension or halothane inhalation in sheep
      anaesthetized with pentobarbital.
AB  - We have studied the mechanism whereby halothane induces adrenocortical activity
      in eight sheep anaesthetized twice for 2 h with pentobarbital. During the second
      hour they received infusion of nitroprusside to lower mean arterial pressure by
      40 mm Hg (group NP) or on another occasion they inhaled 0.5% halothane (group
      HAL). Plasma concentrations of cortisol, adrenocorticotrophic hormone (ACTH),
      arginine vasopressin (AVP), glucose and lactate were measured. Infusion of
      nitroprusside increased cortisol concentrations from mean 44 (SD 33) to 256 (131)
      nmol litre-1 (P < 0.05), AVP from 19 (14) to 174 (102) pmol litre-1 (P < 0.05)
      and ACTH from 30 (17) to 54 (32) pmol litre-1. Glucose and lactate concentrations
      did not change significantly. After 60 min of halothane administration, there
      were fewer effects: plasma cortisol increased from 47 (39) to 63 (44) nmol litre
      1 (P > 0.05) and AVP from 14 (11) to 32 (29) pmol litre-1 (P > 0.05) while ACTH
      decreased from 32 (13) to 25 (10) pmol litre-1. The AUC60-120 values for all
      three hormones were significantly lower in group HAL than in group NP (P < 0.01).
      Glucose was unchanged but lactate concentration decreased. These results support,
      but do not prove, the hypothesis that hypotension is the main stimulus to
      pituitary-adrenocortical activity during halothane anaesthesia in sheep. A direct
      effect of nitroprusside cannot be ruled out.

PMID- 9602588
TI  - Production of nitrogen dioxide in a delivery system for inhalation of nitric
      oxide: a new equation for calculation.
AB  - We have evaluated the kinetics of nitrogen dioxide production in a system for
      inhalation of nitric oxide. In addition to a small fraction of contamination of
      nitrogen dioxide in the nitric oxide stock gas, a considerable part of the total
      concentration of nitrogen dioxide is formed immediately after mixing of nitric
      oxide and oxygen. This initial build-up of nitrogen dioxide is followed by a
      linear, time-dependent increase in the concentration of nitrogen dioxide. An
      equation describing the concentration of nitrogen dioxide in the delivery system
      is formulated: [NO2] = kA x [NO] + kB x [NO]2 x [O2] + kC x t x [NO]2 x [O2],
      where nitrogen dioxide [NO2] and nitric oxide [NO] concentrations are in parts
      per million (ppm), oxygen concentration [O2] is expressed as a percentage and
      contact time (t) is in seconds. The rate constants are kA = 5.12 x 10(-3), kB =
      1.41 x 10(-6) and kC = 0.86 x 10(-6). Calculated nitrogen dioxide values
      correlated well with measured concentrations. This new finding of an initial
      build-up of nitrogen dioxide has to be taken into consideration if the conversion
      of nitric oxide to nitrogen dioxide is to be calculated and in the safety
      guidelines for the use of nitric oxide.

PMID- 9602589
TI  - Lidocaine increases the ventricular fibrillation threshold during bupivacaine
      induced cardiotoxicity in pigs.
AB  - Ventricular fibrillation (VF) is a cause of death in bupivacaine-induced
      cardiovascular toxicity. We have examined the therapeutic effects of lidocaine on
      the threshold for bupivacaine-induced VF in in situ beating swine hearts. Twenty
      four animals were allocated to one of three groups: 0.25% bupivacaine, 1%
      lidocaine or 0.25% bupivacaine with 1% lidocaine were infused into the left
      anterior descending coronary artery in increasing doses of 0, 1, 2, 4, 8 and 16
      ml h-1 for 15 min, respectively. ECG and haemodynamic variables were monitored
      continuously during infusion. Regional myocardial function in the area supplied
      by the left anterior descending coronary artery was assessed using the
      sonomicrometry technique. VF did not occur in the lidocaine group. VF developed
      at higher infusion rates in animals given bupivacaine with lidocaine (in one
      animal at an infusion rate of 8 ml h-1 and in seven at 16 ml h-1) compared with
      animals given bupivacaine alone (in one at an infusion rate of 4 and in seven at
      8 ml h-1). Although regional myocardial function decreased with increases in the
      infusion rate in each group, the depressant effects of the bupivacaine solution
      (medial inhibitory infusion rate of systolic shortening: IR50 = 2.43 (0.43) ml h
      1) were significantly greater than those of the lidocaine solution (IR50 = 5.83
      (0.87) ml h-1), but did not differ from those of the bupivacaine with lidocaine
      solution (IR50 = 3.54 (0.56) ml h-1). This study indicates that a combination of
      lidocaine and bupivacaine increased the threshold for bupivacaine-induced VF
      without further depressing myocardial contractility.

PMID- 9602590
TI  - Anaesthesia for telescopic procedures in the thorax.

PMID- 9602591
TI  - Comparison of intubating conditions after rocuronium or vecuronium when the
      timing of intubation is judged by clinical criteria.
AB  - The onset of action and intubating conditions after rocuronium 0.6 mg kg-1 or
      vecuronium 0.1 mg kg-1 were compared in a randomized, double-blind study when the
      timing of tracheal intubation was determined by clinical judgment alone. Times to
      laryngoscopy and completion of intubation were mean 89 (SD 20) s and 119 (28) s,
      respectively, in the rocuronium group compared with 110 (26) s and 142 (32) s in
      the vecuronium group (P < 0.05 in both cases). Recuronium also resulted in
      significantly better intubating conditions compared with vecuronium but with no
      significant reduction in the haemodynamic response to intubation. We found that
      onset of satisfactory intubating conditions after rocuronium was detected
      clinically, although even earlier intubation should be possible by careful timing
      or by neuromuscular monitoring.

PMID- 9602592
TI  - Vecuronium-induced neuromuscular block during xenon or sevoflurane anaesthesia in
      humans.
AB  - Twitch response using accelerometry and plasma concentrations, of vecuronium and
      its metabolite were studied in 27 surgical patients during xenon or sevoflurance
      anaesthesia after administration of vecuronium 0.05 mg kg-1. Anaesthesia was
      maintained using oxygen-xenon (MAC = 71%) or oxygen-sevoflurane (MAC = 2%) at an
      end-tidal concentration equal to 0.8 MAC (i.e. 57% xenon and 1.6% sevoflurane).
      Mean time from administration of vecuronium to 25% recovery of the first twitch
      of the train-of-four response was significantly shorter in the xenon group than
      in the sevoflurane group (12.9 (SD 2.5) min vs 19.4 (6.0) min, respectively).
      Plasma concentrations of vecuronium at 25% recovery were significantly higher
      during xenon than during sevoflurane anaesthesia (187 (49) ng ml-1 vs 136 (40) ng
      ml-1, respectively), while those of 3-desacetylvecuronium were similar in both
      groups.

PMID- 9602593
TI  - Current practice of local anaesthesia for routine ocular surgery.
AB  - We surveyed the current practice of local anaesthesia for routine ocular surgery
      by consultant anaesthetists in the Wessex region using a postal questionnaire.
      Most consultants were in agreement concerning the type and technique of block,
      and monitoring to be used during local anaesthesia for ocular surgery. The issue
      of teaching for trainee anaesthetists produced a varied response. We found that a
      different level of perioperative preparation and monitoring was used from that
      recommended by the Joint Working Party on the subject in 1993.

PMID- 9602594
TI  - Desflurane maintains intraocular pressure at an equivalent level to isoflurane
      and propofol during unstressed non-ophthalmic surgery.
AB  - We have investigated the effects of desflurane compared with isoflurane and
      propofol on intraocular pressure (IOP) in 48 ASA I-II patients undergoing
      elective non-ophthalmic surgery. Anaesthesia was induced with thiopental 3-5 mg
      kg-1, fentanyl 2-4 micrograms kg-1 and vecuronium 0.1 mg kg-1. Patients were
      allocated randomly to receive propofol (n = 16) 4-8 mg kg-1 h-1, isoflurane (n =
      16) or desflurane (n = 16) for maintenance of anaesthesia. Fentanyl was added if
      necessary. The lungs were ventilated with 70% nitrous oxide in oxygen. Arterial
      pressure, electrocardiography, heart rate and end-tidal carbon dioxide were
      measured throughout anaesthesia. IOP was measured before surgery, during
      maintenance and after emergence from anaesthesia with applanation tonometry by an
      ophthalmologist blinded to the anaesthetic technique. There was a significant
      decrease in IOP after induction of anaesthesia which did not differ between
      groups. Desflurane maintained IOP at an equivalent level to isoflurane and
      propofol.

PMID- 9602595
TI  - Intraperitoneal bupivacaine or lidocaine does not provide analgesia after total
      abdominal hysterectomy.
AB  - We have compared pain scores at rest and on standardized movement, and morphine
      consumption using patient-controlled analgesia in 60 patients who had undergone
      total abdominal hysterectomy. Patients were allocated randomly to one of three
      groups: in the saline group, 0.9% sodium chloride 50 ml was administered into the
      pelvic cavity before closure of the peritoneum; in the second group, the solution
      administered was 20 ml of 0.5% bupivacaine solution with epinephrine 1:200,000
      diluted with saline to a final volume of 50 ml; in the third group, the solution
      used was 20 ml [corrected] of 2% lidocaine with epinephrine 1:200,000 diluted
      with saline to a final volume of 50 ml. We found that there was no significant
      difference between the three groups in visual analogue pain scores at 8, 12, 36
      or 48 h after operation at rest or on movement, and no significant difference in
      sedation or dose of antiemetic administered. Mean morphine consumption in the
      first 24 h was 54.6 (SEM 5.9) mg in the saline group, 55.5 (6.4) mg in the
      bupivacaine group and 52.5 (5.3) mg in the lidocaine group. In the second 24 h,
      morphine consumption was 34.9 (6.6) mg, 28.1 (3.5) mg and 28.0 (3.5) mg in the
      three groups, respectively. We conclude that i.p. administration of local
      anaesthetic solution into the pelvic cavity did not confer appreciable analgesia
      in patients undergoing abdominal hysterectomy.

PMID- 9602596
TI  - Prevention of postoperative nausea and vomiting in female patients during
      menstruation: comparison of droperidol, metoclopramide and granisetron.
AB  - The incidence of postoperative nausea and vomiting (PONV) is high in women during
      menstruation. We have compared the efficacy of droperidol, metoclopramide and
      granisetron in the prevention of PONV in female patients during menstruation
      undergoing major gynaecological surgery. In a randomized, double-blind study, 120
      patients received droperidol 25 micrograms kg-1, metoclopramide 0.2 mg kg-1 or
      granisetron 40 micrograms kg-1 (n = 40 in each group) i.v. immediately before
      induction of anaesthesia. A standard general anaesthetic technique and
      postoperative analgesia were used throughout. There was a complete response,
      defined as no PONV and no administration of rescue medication, during the 24-h
      observation period in 45% of patients in the droperidol group, 38% in the
      metoclopramide group and 70% in the granisetron group (P = 0.021 vs droperidol, P
      = 0.003 vs metoclopramide). There was no difference in the incidence of adverse
      events between groups. We conclude that the prophylactic antiemetic efficacy of
      granisetron was superior to that of droperidol or metoclopramide for prevention
      of PONV in women during menstruation.

PMID- 9602597
TI  - Effects of isoflurane-nitrous oxide anaesthesia on insulin secretion in female
      patients.
AB  - In vitro studies suggest that volatile anaesthetic agents may directly inhibit
      insulin secretion. It is unclear if supplementation of anaesthesia with
      isoflurane impairs insulin secretion. We performed a 5-g i.v. glucose tolerance
      test in 21 patients before and during anaesthesia which was maintained with
      either 1 or 2 MAC of isoflurane in nitrous oxide, or no volatile agent. The study
      was carried out before surgery to avoid the influence of hormonal responses to
      trauma. A significant glycaemic response occurred during both i.v. glucose
      tolerance tests in all three groups of patients. Serum insulin concentrations
      were measured and the acute increase in insulin concentration at 3 min and area
      under the curve for 15 min were calculated. Both variables decreased
      significantly in all three groups during the tests performed under anaesthesia
      compared with tests carried out before anaesthesia.

PMID- 9602598
TI  - Relationship between end-tidal and arterial carbon dioxide partial pressure using
      a cuffed oropharyngeal airway and a tracheal tube.
AB  - We have compared the differences between end-tidal PE'CO2 and arterial PaCO2
      carbon dioxide partial pressures during general anaesthesia using either a cuffed
      oropharyngeal airway (COPA) or a tracheal tube (TT) in spontaneously breathing
      adult patients. After induction of anaesthesia, a COPA was inserted in 20
      patients who were allowed to breathe spontaneously. When steady state was
      reached, PE'CO2 and PaCO2 were recorded. The COPA was removed, the trachea
      intubated with a TT and spontaneous ventilation allowed to resume. After a stable
      PE'CO2 was reestablished, PaCO2 was measured again and PE'CO2 recorded. Mean
      difference between PaCO2 and PE'CO2 with the COPA was 0.72 (SD 0.45) kPa and with
      the TT 0.64 (0.40) kPa (ns; paired t test). Our results suggest that Pe'CO2 is a
      clinically acceptable indicator of PaCO2 in adults breathing spontaneously via a
      COPA.

PMID- 9602599
TI  - The blood-gas partition coefficient of xenon may be lower than generally
      accepted.
AB  - The blood-gas partition coefficients of xenon, reported more than 25 yr ago in
      the literature, vary considerably from 0.13 to 0.20. Consequently, we have
      determined this variable by directly injecting xenon-saturated blood into a gas
      chromatograph-mass spectrometer. This technique yielded a blood-gas partition
      coefficient for xenon of 0.115 (95% confidence interval 0.107-0.123). The
      solubility in water measured identically was 0.096, consistent with the reported
      value of 0.085. These data and a detailed review of the literature strongly
      suggest that the blood-gas partition coefficient of xenon may be lower than the
      generally accepted value of 0.14.

PMID- 9602600
TI  - Sevoflurane has less effect than halothane on pulmonary afferent activity in the
      rabbit.
AB  - We have compared the effects of sevoflurane and halothane on the discharge
      frequencies of 19 slowly adapting and four rapidly adapting lung receptors in the
      rabbit by recording from single vagal fibres. Both agents reduced the discharge
      frequency of slowly adapting receptors during expiration (P < 0.0005), halothane
      having a greater effect than sevoflurane (P < 0.0005). Neither agent had any
      effect on discharge frequency at the end of inspiration when discharge frequency
      is at a maximum. Neither agent affected the discharge frequency of rapidly
      adapting receptors.

PMID- 9602601
TI  - Propofol and electroconvulsive therapy in a patient at risk from acute
      intermittent porphyria.
AB  - A severely depressed 57-yr-old woman at risk from acute intermittent porphyria
      presented for a course of electroconvulsive therapy. With propofol as the
      induction agent the course of electroconvulsive therapy was both uneventful and
      successful.

PMID- 9602602
TI  - The elimination of rebreathing in various semi-closed anaesthetic systems. 1954.

PMID- 9602603
TI  - Tracheal intubation in trauma.

PMID- 9602604
TI  - Calculating catecholamine extraction from plasma.

PMID- 9602605
TI  - Extradural buprenorphine and breast feeding after caesarean section.

PMID- 9602606
TI  - Why the Y?

PMID- 9602607
TI  - Propofol in paediatric intensive care: further evaluation is justified.

PMID- 9602608
TI  - Sevoflurane in acute airway obstruction.

PMID- 9602609
TI  - Sevoflurane in acute airway obstruction.

PMID- 9602610
TI  - Anaesthesia for surgery of emphysema.

PMID- 9602611
TI  - Suboptimal use of inhaled aerosol therapy during mechanical ventilation in
      intensive therapy units in the UK and Ireland.

PMID- 9602612
TI  - From the outside in, or the inside out. Resecting uveal melanomas.

PMID- 9602613
TI  - Ophthalmologists should consider the causes of myopia and not simply treat its
      consequences.

PMID- 9602614
TI  - Endoresection of choroidal melanoma.
AB  - AIMS: The results of 52 endoresections for choroidal melanoma are reported.
      METHODS: The current technique involves vitrectomy, retinal incision over or
      peripheral to the tumour, haemostasis by raising intraocular pressure and by
      moderate hypotensive anaesthesia, choroidal incision around tumour, endoresection
      with vitrector, endodiathermy to bleeding points and residual tumour, fluid-air
      exchange to reattach retina, endolaser to achieve retinal adhesion around the
      coloboma and destroy residual tumour in the sclera, silicone oil injection with
      removal after 12 weeks, cryotherapy to the sclerotomies, and adjunctive ruthenium
      plaque radiotherapy in selected cases. RESULTS: Patients receiving primary
      endoresection had a mean age of 53 years, a mean largest basal tumour diameter of
      8.2 mm, and a mean tumour thickness of 3.9 mm. 40 tumours extended to within 2
      disc diameters of the optic disc, with 17 involving disc. Follow up ranged from
      40 days to 7 years (median 20 months). At the last visit, 90% of eyes were
      retained, with vision of 6/6-6/12 (two), 6/18-6/36 (three), 6/60 to counting
      fingers (18), hand movements (nine), and light perception (four). The main
      complications were retinal detachment in 16 and cataract in 25. Secondary
      endoresection (11) was performed after plaque radiotherapy (four),
      photocoagulation (four), trans-scleral local resection (two), and proton beam
      radiotherapy (one), with retention of the eye in nine cases. By the close of the
      study, no patients developed definite local tumour recurrence but one died of
      metastatic disease 41 months postoperatively. CONCLUSION: Depending on tumour
      location, endoresection may conserve central vision or temporal field when
      radiotherapy would be expected to cause optic neuropathy. Longer follow up is
      necessary to establish the efficacy of tumour control.

PMID- 9602615
TI  - Clinical characteristics of microtropia--is microtropia a fixed phenomenon?
AB  - BACKGROUND/AIMS: Microtropia is believed to be a static condition, in which
      accepted achievable levels of vision are those of 6/12-6/9 maximum, with the
      inability to achieve "normal" levels of stereopsis. The aim of this paper was to
      present the results of treatment of 30 consecutively presenting primary
      microtropes, and assess their outcomes using a more active treatment strategy
      than that conventionally used. METHODS: Visual acuity, stereoacuity, fixation,
      and the presence of a central suppression scotoma were assessed in all patients
      before, during, and after treatment, which comprised wearing maximum refractive
      correction, and an occlusion strategy aiming for equal visual acuity. RESULTS:
      Equal visual acuity of 6/5 Snellen was achieved in 43% of the 30 patients, while
      87% achieved 6/9 Snellen or better visual acuity in the microtropic eye.
      Stereoacuity of better than 60" of arc was attained in 37%, and foveal fixation
      on visuscopy in 55%. The treatment outcome was not affected by the patient's age,
      initial visual acuity, or the amount of anisometropia. A change in the patient's
      diagnosis was noted in 50%, with nine patients recovering completely.
      CONCLUSIONS: The results show that microtropia is not static. Equal 6/5 vision is
      attainable, as is high grade stereoacuity. The pattern of fixation may change
      during treatment and elimination of the microtropia is possible in some cases.
      There is a requirement for management protocols to be changed in order to treat
      this condition more effectively.

PMID- 9602616
TI  - Recovery in microtropia: implications for aetiology and neurophysiology.
AB  - AIMS/BACKGROUND: The basis of binocular single vision in microtropia remains a
      matter of contention. This paper discusses the implications of recovery, in a
      group of primary microtropes following treatment, in relation to current concepts
      on the aetiology of the condition and proposed retinocortical correspondence.
      METHODS: Nine previously untreated primary microtropes whose condition resolved,
      were reviewed in detail to assess the patterns of change in retinal
      correspondence, uniocular fixation, stereoacuity, and visual acuity in response
      to treatment. RESULTS: Anomalous retinal correspondence (ARC), a central scotoma,
      reduced or absent stereoacuity, amblyopia, and uniocular eccentric fixation were
      present in all patients before treatment. Following treatment, all cases attained
      normal retinal correspondence (NRC), elimination of the central scotoma, stereo
      acuity levels of between 20 and 40 seconds of arc, 6/5 Snellen visual acuity in
      both eyes, and foveal fixation in both eyes. CONCLUSION: A hypothesis is put
      forward that for the patients described, a period of normal development is likely
      to have preceded the onset of microtropia, during which the retinocortical
      "foundations" for NRC were established. Precise pairing of foveo-foveal receptive
      fields was not abolished by the presence of amblyopia and a central scotoma, but
      this relation was temporarily suspended and binocular single vision was sustained
      via the neural substrate of paired receptive fields over a wide retinocortical
      area.

PMID- 9602617
TI  - Epidemic optic neuropathy in primary school children in Dar es Salaam, Tanzania.
AB  - BACKGROUND: An epidemic of bilateral optic neuropathy is affecting large numbers
      of people aged between 10 and 40 in Dar es Salaam, the capital city of Tanzania.
      The disease is characterised by acute onset of bilateral visual impairment,
      bilateral impairment of colour vision, and a characteristic temporal pallor of
      the optic discs. The disease often occurs in association with peripheral
      neuropathy and sensorineural hearing loss. This report presents the first data on
      disease prevalence in adolescents, based on a rapid assessment of schoolchildren.
      METHODS: Three schools in Dar es Salaam were visited and all children aged
      between 10 and 16 were screened for the disease. RESULTS: The prevalence of
      bilateral optic neuropathy among the schoolchildren is estimated to be 1.0% (95%
      CI 0.5-1.4%). This suggests that 5000 children (95% CI 2600-7300) aged 10-16 in
      Dar es Salaam may have the disease. CONCLUSION: The results of this rapid
      assessment indicate this epidemic is a major public health problem. The
      prevalence of the disease in the community is likely to be far higher than found
      in this survey because children with the disease may have withdrawn from school.
      As the disease predominantly affects young adults, resulting in impaired vision
      and hearing, the economic and social consequences are enormous.

PMID- 9602618
TI  - Transplantation of amniotic membrane and limbal autograft for patients with
      recurrent pterygium associated with symblepharon.
AB  - AIM: Treatment of recurrent pterygium associated with symblepharon requires both
      suppression of fibrosis and reconstruction of limbal barrier. To achieve this,
      human amniotic membrane was transplanted and limbal autografts performed.
      METHODS: Four patients with severe symblepharon resulting from multiple surgeries
      for pterygium were treated. Human amniotic membrane was obtained at caesarean
      section and preserved until surgery. After excision of the fibrous tissues, the
      amniotic membrane was placed on the sclera, and a limbal autograft
      transplantation was performed using limbal tissues taken from the affected eye.
      RESULTS: Recurrence of symblepharon was not observed in any of the patients and
      significant suppression of the subconjunctival fibrosis was achieved. Ocular
      movement improved in all cases. Complete remission of pterygium regrowth occurred
      in three cases, and a slight (about 1 mm) recurrence occurred in one case. The
      limbal donor site showed the presence of mild depressions without the formation
      of pseudopterygium. CONCLUSION: Transplantation of human amniotic membrane with a
      limbal autograft appears to be a promising surgical treatment for reconstructing
      the ocular surface in patients with recurrent pterygium associated with
      symblepharon.

PMID- 9602619
TI  - Coexistence of macular corneal dystrophy types I and II in a single sibship.
AB  - BACKGROUND: Macular corneal dystrophy (MCD) is an inherited autosomal recessive
      disorder that has been subdivided into two primary immunophenotypes, MCD types I
      and II. The MCD type I gene has been localised previously to chromosome 16q22 and
      suggestive evidence provided that MCD type II gene is also linked to this region.
      Here an unusual family is reported where both MCD types I and II are found in a
      single sibship. METHODS: Immunoreactivity to an anti-keratan sulphate monoclonal
      antibody (5-D-4) was evaluated in patients' serum and in corneal tissue obtained
      at keratoplasty. Chromosomal haplotypes were constructed using microsatellite
      repeat markers spanning the region of the MCD type I locus. RESULTS:
      Immunological studies demonstrated that two of the affected siblings have MCD
      type II while one has MCD type I. Haplotype analysis suggests that all three
      affected sibs inherited one identical parental haplotype. However, the two MCD
      types differ in their alternative chromosome with both MCD type II children
      sharing an identical haplotype, different from their MCD type I sibling.
      CONCLUSION: The findings in this study support the hypothesis that the genes for
      MCD types I and II co-localise to the same region of chromosome 16 and are likely
      to be due to allelic manifestations of the same abnormal gene.

PMID- 9602620
TI  - Increased presence of Epstein-Barr virus DNA in ocular fluid samples from HIV
      negative immunocompromised patients with uveitis.
AB  - AIMS: To investigate whether routine testing for Epstein-Barr virus (EBV) is
      necessary in the examination of a patient with uveitis. METHODS: Intraocular EBV
      DNA was determined in 183 ocular fluid samples taken from patients with AIDS and
      uveitis, HIV negative immunocompromised uveitis, acute retinal necrosis,
      toxoplasma chorioretinitis, intraocular lymphoma, anterior uveitis, and
      miscellaneous uveitis of unknown cause. In 82 samples from this group of patients
      paired serum/ocular fluid analysis was performed to detect local antibody
      production against EBV. Controls (n = 46) included ocular fluid samples taken
      during surgery for diabetic retinopathy, macular pucker, or cataract. RESULTS:
      Serum antibody titres to EBV capsid antigen proved to be significantly increased
      in HIV negative immunocompromised patients with uveitis (p < 0.01) compared with
      controls. Local antibody production revealed only three positive cases out of 82
      patients tested, two results were borderline positive and one patient had uveitis
      caused by VZV. EBV DNA was detected in three out of 46 control ocular fluid
      samples. In the different uveitis groups EBV DNA was noted, but was not
      significantly higher than in the controls, except in six out of 11 HIV negative
      immunocompromised patients (p = 0.0008). In four out of these six cases another
      infectious agent (VZV, HSV, CMV, or Toxoplasma gondii) had previously been
      identified as the cause of the uveitis. CONCLUSIONS: When comparing various
      groups of uveitis patients, EBV DNA was found more often in HIV negative
      immunocompromised patients with uveitis. Testing for EBV does not have to be
      included in the routine management of patients with uveitis, since indications
      for an important role of this virus were not found in the pathogenesis of
      intraocular inflammation.

PMID- 9602621
TI  - Clinical evaluation of scanning laser polarimetry: I. Intraoperator
      reproducibility and design of a blood vessel removal algorithm.
AB  - AIMS: To evaluate the reproducibility of the retardation values (change in
      polarisation) obtained with the scanning-laser polarimeter in a series of normal
      subjects and glaucoma patients. To improve the analysis of the raw data by
      devising and evaluating a blood vessel removal algorithm. METHODS: Scanning laser
      polarimetry was performed on 10 normal subjects and 10 glaucoma patients. A
      series of six images was obtained from each eye. The normal subjects were re
      imaged 3 months after their initial assessment. The retardation values obtained
      from each eye were analysed using the authors' own methods, including the use of
      an algorithm to remove blood vessels from the polar profiles. The reproducibility
      of these measurements and the performance of the blood vessel removal algorithm
      were assessed. RESULTS: The "individual point" coefficient of variation was
      approximately 12.5% for normal subjects and 17.0% for glaucoma patients. The
      "integral" coefficient of variation for these groups was approximately 5.5% and
      9.5% respectively. The reproducibility of the measurements did not improve with
      an increased number of measurements. There was no difference in the
      reproducibility of the measurements in normal subjects over time. The blood
      vessel removal algorithm improved the reproducibility of the measurements when
      the shape of the profile was assessed. CONCLUSION: The intraoperator
      reproducibility of retardation values obtained with the scanning laser
      polarimeter is satisfactory for its use as a clinical tool. The use of a blood
      vessel removal algorithm improves the reproducibility of the measurements and
      also assists the clinician in the interpretation of the polar profiles.
      Furthermore, it allows the construction of normal database polar profiles,
      thereby enabling the identification, location and quantification of retinal nerve
      fibre layer damage in an "at risk" individual's polar profile.

PMID- 9602622
TI  - Clinical evaluation of scanning laser polarimetry: II. Polar profile shape
      analysis.
AB  - AIMS: To devise a method to describe and quantify the shape of polar profiles
      obtained with the scanning laser polarimeter and to compare this measurement with
      other polar profile measurements in a series of normal subjects and glaucoma
      patients. METHODS: Scanning laser polarimetry was performed on 54 normal subjects
      and 74 glaucoma patients. The retardation values obtained from one randomly
      chosen eye of each subject were analysed using our own methods, including the use
      of an algorithm to remove blood vessels from the polar profiles, an algorithm to
      standardise the glaucoma profiles to a normal database, and a further algorithm
      to evaluate the profile shape. The measurements of profile shape were compared
      with measurements of the absolute and standardised retinal nerve fibre layer
      thickness obtained with the scanning laser polarimeter. RESULTS: There was no
      significant difference between the mean retardation values for the normal and
      glaucomatous subjects in either hemiretina. However, standardisation of the
      glaucoma retardation values to a normal database produced significant differences
      at p < 1 x 10-8 in the mean retardation values for these two groups in both
      hemiretinas. Profile shape measurement analysis produced similar significant
      differences between the mean retardation values for the normal and glaucomatous
      subjects in both hemiretinas, although the degree of separation was greater
      following standardisation of the retardation values. CONCLUSION: The use of an
      algorithm to standardise an individual's retardation values in conjunction with a
      blood vessel removal algorithm enables an improvement in the ability of the
      scanning laser polarimeter to discriminate between normal and glaucomatous
      patients. The polar profile shape algorithm is independent of standardisation and
      significantly improves the discrimination between normal and glaucomatous
      patients, as well as providing additional information regarding the retinal nerve
      fibre layer.

PMID- 9602623
TI  - Multifocal electroretinography in patients with Stargardt's macular dystrophy.
AB  - AIMS: To describe the topography of multifocal electroretinograms (ERGs) and to
      explore its diagnostic value in patients with Stargardt's macular dystrophy
      (SMD). METHODS: 51 patients with SMD were examined by means of the m-sequence
      technique to characterise the topography of electroretinographic responses in the
      central visual field. The results were compared with data from 30 normal
      volunteers. RESULTS: In 49 of 51 patients with SMD, macular electroretinographic
      activity was markedly diminished or non-detectable. Towards more peripheral
      areas, ERG responses of the SMD patients approached those of normals. Implicit
      times were not markedly delayed at any eccentricity. CONCLUSION: In contrast with
      Ganzfeld electroretinography, multifocal electroretinography is useful to detect
      foveal dysfunction in SMD. Areas of dysfunction were found to be usually larger
      than expected from psychophysical measurements and morphological alteration. In
      early stages of the disease it was possible to detect foveal dysfunction, even in
      patients lacking morphological fundus changes and with good visual acuity.

PMID- 9602624
TI  - The nanophthalmic macula.
AB  - AIMS: To define an unusual macular appearance found in association with
      nanophthalmos. METHODS: A case review. RESULTS: Seven children (aged 8 months to
      17 years) with nanophthalmos were examined. They all exhibited the same clinical
      findings of an unusual yellow macula appearance with retinal folds and crowded
      optic discs. Visual electrophysiology performed in four cases was normal.
      CONCLUSION: A distinctive yellow macular pigmentation with associated
      chorioretinal folds and crowded optic discs is present in nanophthalmos. It is
      proposed that the retinal folds are due to a disparity between scleral and
      retinal growth while the macula discoloration is due to a congenital abnormality
      in arrangement or position of the luteal pigment and is not degenerative.
      Included in this case series is the second case in the literature of
      nanophthalmos associated with Kenny's syndrome. Inheritance of nanophthalmos
      appears to be autosomal recessive.

PMID- 9602625
TI  - Helicoidal peripapillary chorioretinal degeneration: electrophysiology and
      psychophysics in 17 patients.
AB  - AIMS: To characterise retinal function using electrophysiological and
      psychophysical tests in 17 patients with helicoidal peripapillary chorioretinal
      degeneration. METHODS: The electroretinogram (ERG) was recorded using gold foil
      corneal electrodes. The electro-oculogram (EOG) was recorded using a standard
      protocol. Dark adaptometry was recorded with an SST-1 dark adaptometer and colour
      vision assessed with Ishihara plates and Farnsworth D-15. RESULTS: All subjects
      had a recordable ERG. The amplitudes and implicit times of the a- and b-waves
      were within normal limits at all luminances in five subjects (age 21-70 years,
      mean 40 years). The ERG of six (age 26-55 years, mean 40.7 years) had subnormal
      amplitudes at all luminances, but normal implicit times, and six (age 38-81
      years, mean 60.7 years) had abnormal ERGs with marked reduction of a- and b
      waves, and delayed implicit times of the b-wave. The implicit times of the a-wave
      were normal in all subjects. A reduction in the b/a wave ratios was not found,
      nor was there selective loss of scotopic, mixed rod/cone, or cone responses. The
      light/dark ratio of the EOG was subnormal (150-185%) or abnormal (below 150%) in
      all but three subjects. Two patients with normal EOG showed normal ERGs in both
      eyes, but one had subnormal ERGs in both eyes. The scotopic sensitivity was
      normal in all subjects and dark adaptation showed a normal time course. Colour
      vision was normal in all patients. CONCLUSION: The results suggest that in most
      cases the function of the retinal pigment epithelium is affected by this disease
      before any changes in the function of the sensory retina are detectable by our
      methods, and that retinal dysfunction is focal rather than diffuse.

PMID- 9602626
TI  - Histomorphometry of the optic disc in highly myopic eyes with absolute secondary
      angle closure glaucoma.
AB  - AIM: To evaluate histomorphometrically the optic nerve head in highly myopic eyes
      with absolute secondary angle closure glaucoma. METHODS: Optic disc sections of
      16 highly myopic eyes with an axial length of more than 26 mm and of 19 eyes with
      an axial length of less than 26 mm were histomorphometrically evaluated. All eyes
      had been enucleated due to painful absolute secondary angle closure glaucoma.
      RESULTS: In the highly myopic eyes compared with the non-highly myopic eyes, mean
      optic disc diameter was significantly larger (mean 2.33 (SD 0.55) mm versus 1.77
      (0.50) mm; p = 0.01), and the optic cup was significantly shallower (optic cup
      depth 0.34 (0.29) mm versus 0.63 (0.23) mm; p = 0.03). The peripapillary scleral
      ring was significantly broader (0.58 (0.65) mm versus 0.08 (0.06) mm; p = 0.001),
      and the beta zone (0.83 (0.74) mm versus 0.28 (0.25) mm; p = 0.006) of the
      parapapillary chorioretinal atrophy was significantly larger in the highly myopic
      eyes. CONCLUSIONS: The results of the present study agree with biomorphometric
      data of the optic nerve head in highly myopic eyes with glaucoma. In the highly
      myopic group, a markedly enlarged peripapillary scleral ring characterised by
      absence of Bruch's membrane and choriocapillaris contributes in addition to alpha
      and beta zone to the parapapillary atrophy.

PMID- 9602627
TI  - Optic disc anomalies and frontonasal dysplasia.
AB  - AIMS: To document the optic disc abnormalities in patients with frontonasal
      dysplasia in association with basal encephalocele. METHODS: Names and hospital
      numbers of patients with midline clefts were obtained from the ophthalmology and
      genetics database. Six patients were identified who had the following common
      findings: midline facial cleft with midline cleft lip and palate; hypertelorism;
      absent corpus callosum; basal (sphenoethmoidal) encephalocele; and pituitary
      deficiency (five out of six cases). Ophthalmic examination was performed with
      fundal photography where possible. RESULTS: Two patients had unilateral and one a
      bilateral peripapillary staphyloma. Two patients had bilateral optic disc
      hypoplasia and one appeared to have a peripapillary staphyloma in one eye and a
      morning glory disc in the other. CONCLUSION: Optic disc abnormalities were found
      in all patients with this constellation of clinical findings. This association
      appears to represent a distinct subgroup within the spectrum of frontonasal
      dysplasia. The presence of midline facial anomalies and any dysplastic disc
      should alert the physician as to the presence of an encephalocele.

PMID- 9602628
TI  - A murine model of interlamellar corneal transplantation.
AB  - AIMS/BACKGROUND: There are more reagents and information available for
      immunological studies in the mouse compared with other animals. Unfortunately,
      the mouse penetrating keratoplasty model is associated with high background
      inflammation which hinders study of the immune response to the graft. To mitigate
      this drawback, a murine orthotopic corneal interlamellar transplantation model
      with mild non-specific inflammation was developed. METHODS: A 1.5 mm diameter
      full thickness donor corneal button was placed in a 2 mm diameter recipient
      corneal interlamellar pocket without placement of a suture. The clinical course
      of graft status was studied daily for 60 days in 30 allografts (donor strain CBA
      101 (H-2k) to recipient NIH (H-2q) and 30 syngeneic grafts (NIH to NIH) by slit
      lamp biomicroscopy and scored for neovascularisation, opacity, oedema, and
      granularity. In another cohort of animals, histological observation was performed
      after 30 minutes and on days 10, 20, 30, and 40 after transplantation (four
      allografts and four syngeneic grafts per time point). Histological study was also
      performed on grafts without donor epithelium and on interlamellar pockets without
      grafts. RESULTS: There was significantly more neovascularisation (NV), opacity,
      oedema, and granularity in 24/30 allografts (80%) than in syngeneic grafts. Such
      grafts were defined as rejected. The median time to rejection was 21 days (range
      18 to > 60 days). By histology, some allografts showed moderate to heavy cell
      infiltration which correlated with clinical scores of NV (4-5), opacity (1-3),
      oedema (1-3), and granularity (1-3). Such infiltration was absent in other
      allografts and syngeneic grafts. CONCLUSION: Surgically, corneal interlamellar
      transplantation could be accomplished in the mouse and rejection could be clearly
      defined. The model can therefore be useful for in situ study of cell and
      molecular aspects of corneal graft rejection.

PMID- 9602629
TI  - Corneal aldehyde dehydrogenase and glutathione S-transferase activity after
      excimer laser keratectomy in guinea pigs.
AB  - BACKGROUND: The free radical balance of the eye may be changed by excimer laser
      keratectomy. Previous studies have demonstrated that excimer laser keratectomy
      increases the corneal temperature, decreases the superoxide dismutase activity of
      the aqueous, and induces lipid peroxidation in the superficial corneal stroma.
      Aldehyde dehydrogenase (ALDH) and glutathione S-transferase (GST) are known to
      play an important role in corneal metabolism, particularly in detoxification of
      aldehydes, which are generated from free radical reactions. METHODS: In three
      groups of guinea pigs mechanical corneal de-epithelialisation was performed in
      group I, superficial corneal photoablation in group II, and deep corneal
      photoablation in group III, and the corneal ALDH and GST activities measured
      after 48 hours. RESULTS: The mean ALDH and GST activities of group I and II
      showed no differences compared with the controls (p > 0.05). The corneal ALDH
      activities were found to be significantly decreased (p < 0.05) and GST activities
      increased (p < 0.05) in group III. CONCLUSION: These results suggest that excimer
      laser treatment of high myopia may change the ALDH and GST activities,
      metabolism, and free radical balance of the cornea.

PMID- 9602630
TI  - Role of impression cytology during hypovitaminosis A.
AB  - AIMS: Evaluation of the morphological damage to the ocular surface of patients
      operated for biliopancreatic diversion for pathological obesity and the
      correlation of impression cytology with vitamin A plasma levels, adaptometry, and
      other general variables. METHODS: 48 patients (15 males, 33 females, age range 21
      73) and 34 normal subjects were examined with fluorescein and rose bengal, a
      plasma dose of vitamin A, and adaptometry. The results of the various tests were
      subdivided into three levels (0 = normal, 1 = moderately altered, 2 = seriously
      altered). The impression cytology and adaptometry results were correlated with
      vitamin A levels and other patient data (age, nutritional condition, time since
      operation, percentage weight loss). All the examinations were repeated after
      intramuscular therapy with vitamin A. RESULTS: Corneoconjunctival alterations
      visible with fluorescein and rose bengal staining were present in 67.7% of cases,
      impression cytology alterations in 93.7%, adaptometric alterations in 82.2%;
      vitamin A plasma levels were below normal in 95.8% of cases. After the therapy
      with vitamin A a significant reduction was found for every examination. The
      correlation between impression cytology and adaptometry and vitamin A plasma
      levels and between corneoconjunctival alterations and vitamin A plasma levels was
      significant. There was no significant correlation between impression cytology and
      nutritional condition, age time since operation, and percentage weight loss.
      CONCLUSION: These results show impression cytology is a specific indicator for
      hypovitaminosis A because it is not influenced by other factors related to the
      general condition of the patient. Many patients with hypovitaminosis A not
      demonstrating ocular symptoms of changes visible with fluorescein and rose bengal
      showed alterations with impression cytology.

PMID- 9602631
TI  - Diagnosis of Fusarium keratitis in an animal model using the polymerase chain
      reaction.
AB  - AIMS/BACKGROUND: The purpose of this study was apply the polymerase chain
      reaction (PCR) to develop a sensitive, specific, and rapid test to diagnose
      Fusarium keratitis. Fusarium is the most common cause of fungal corneal infection
      in some parts of the world. It is often difficult to establish that a keratitis
      is due to fungal infection. METHODS: Fusarium solani keratitis was induced in
      three eyes of three rabbits by injection of a suspension of the fungus into the
      anterior corneal stroma. In one rabbit the contralateral eye served as a control.
      From four to 28 days after inoculation, the corneas were scraped for culture,
      then scraped and swabbed for PCR analysis. The PCR was performed with primers
      directed against a portion of the Fusarium cutinase gene, and the presence or
      absence of this amplified target sequence was determined by agarose gel. RESULTS:
      The amplified DNA sequence was detected in 25 of 28 samples from the corneas
      infected with Fusarium, for a sensitivity of 89%. Only three of the 14 samples
      from these eyes with Fusarium keratitis were positive by culture, for a
      sensitivity of 21%. Seven of eight control samples were negative by the PCR based
      test, for a specificity of 88%. CONCLUSION: This PCR based test holds promise of
      being an effective method of diagnosing Fusarium keratitis as well as Fusarium
      infections at other sites.

PMID- 9602632
TI  - Eosinophil granule proteins expressed in ocular cicatricial pemphigoid.
AB  - BACKGROUND: Blister formation and tissue damage in bullous pemphigoid have been
      attributed to the release of eosinophil granule proteins--namely, to eosinophil
      derived cationic protein (ECP) and major basic protein (MBP). In the present
      investigation these eosinophil granule proteins were studied in the conjunctiva
      of patients with ocular cicatricial pemphigoid (OCP). METHODS: Conjunctival
      biopsy specimens obtained from patients with subacute (n = 8) or chronic
      conjunctival disease (n = 13) were analysed histologically and
      immunohistochemically using antibodies directed against EG1 (stored and secreted
      ECP), EG2 (secreted ECP), MBP, CD45 (common leucocyte antigen), CD3 (pan T cell
      marker), and HLA-DR (class II antigen). RESULTS: Subepithelial mononuclear cells,
      mast cells, and neutrophils were detected in all specimens. The number of
      mononuclear cells, neutrophils, CD45+ cells, CD3+ cells, and the HLA-DR
      expression were significantly higher in the subacute than in the chronic disease
      group. Some eosinophils were found in specimens from five of eight patients with
      subacute OCP, but in none of the patients with chronic disease. The eosinophil
      granule proteins (ECP and MBP) were found in the epithelium and substantia
      propria in patients with subacute conjunctivitis. CONCLUSIONS: Subepithelial cell
      infiltration in the conjunctiva greatly differs between subacute and chronic
      ocular cicatricial pemphigoid specimens. The findings suggest that eosinophil
      granule proteins may participate in tissue damage in acute phase of inflammation
      in OCP.

PMID- 9602633
TI  - Orbital fibroblast chemokine modulation: effects of dexamethasone and cyclosporin
      A.
AB  - AIM: Orbital inflammation is common, but the mechanisms underlying leucocytic
      infiltration of orbital tissue are poorly understood. Human orbital fibroblasts
      (OF) express chemokines, interleukin 8 (IL-8) and monocyte chemotactic protein 1
      (MCP-1), when exposed to proinflammatory cytokines. The effect of dexamethasone
      (DEX) and cyclosporin A (CSA) on OF IL-8 and MCP-1 were examined. METHODS:
      Cultured human OF were incubated with recombinant interleukin 1 beta (rIL-1 beta;
      0.2, 2.0, 20 ng/ml) alone or incubated with rIL-1 beta and DEX (10(-8), 10(-7),
      10(-6) M) or CSA (3, 30, 300 ng/ml) for 24 hours. ELISA and northern blot
      analyses were performed to determine OF IL-8 and MCP-1 protein secretion and mRNA
      expression, respectively. RESULTS: OF lacked constitutive IL-8 or MCP-1
      expression, but secreted significant amounts of these chemokines and expressed
      substantial steady state mRNA for both chemokines upon rIL-1 beta stimulation.
      DEX caused dose dependent inhibition of IL-1 induced IL-8 (p < 0.001) and MCP-1
      (p < 0.05) secretion and mRNA expression at all concentrations of rIL-1 beta. CSA
      enhanced IL-1 induced OF IL-8 (p < 0.001) and suppressed rIL-1 beta induced OF
      MCP-1 (p < 0.05) secretion when lower doses of rIL-1 beta were used. These
      effects on secreted chemokines at different concentrations of rIL-1 beta and
      immunomodulating agents were corroborated by steady state OF IL-8 and MCP-1 mRNA
      expression. CONCLUSIONS: DEX is a potent inhibitor of OF IL-8 and MCP-1. In
      contrast, CSA enhances IL-1 induced OF IL-8 and suppresses OF MCP-1. These
      observations may explain the relative lack of CSA effectiveness in human orbital
      diseases that respond to corticosteroids.

PMID- 9602635
TI  - Partial lipodystrophy with associated fundus abnormalities: an optical coherence
      tomography study.

PMID- 9602634
TI  - Interferon associated retinopathy.

PMID- 9602636
TI  - Unusual macular retinal detachment associated with vitreomacular traction
      syndrome.

PMID- 9602637
TI  - Steroid responsive disc neovascularisation in uveitis associated with juvenile
      chronic arthritis.

PMID- 9602638
TI  - Scleritis associated with acute febrile neutrophilic dermatosis (Sweet's
      syndrome)

PMID- 9602639
TI  - Cornea plana--clinical features, videokeratometry, and management.

PMID- 9602640
TI  - Primary epithelial amyloid keratopathy with multiple recurrences in grafts.

PMID- 9602641
TI  - Shared care postoperative management of cataract patients.

PMID- 9602642
TI  - Peripapillary circle of Zinn-Haller revealed by fundus fluorescein angiography.

PMID- 9602643
TI  - Sustained release intravitreal ganciclovir implant as salvage treatment in AIDS
      related cytomegalovirus retinitis.

PMID- 9602644
TI  - Complications of fascia lata harvesting for ptosis surgery.

PMID- 9602645
TI  - Stenting of systemic venous pathways after atrial repair for complete
      transposition.

PMID- 9602646
TI  - The Fontan procedure: lessons from the past.

PMID- 9602647
TI  - How to treat small coronary vessels with angioplasty.

PMID- 9602648
TI  - Dual chamber single lead pacing.

PMID- 9602649
TI  - Atherosclerosis and myocardial infarction.

PMID- 9602650
TI  - Are patients with poor left ventricular function more prone to oxidative stress
      during cardiac surgery?

PMID- 9602651
TI  - Residual and recurrent shunts after implantation of Cook detachable duct
      occlusion coils.
AB  - OBJECTIVE: To assess the presence and outcome of Doppler detectable shunts
      following implantation of the Cook detachable PDA coil. DESIGN: Prospective
      study. SETTING: Tertiary paediatric cardiac centre. PATIENTS: 76 consecutive
      patients undergoing coil implantation (80 procedures). MAIN OUTCOME MEASURES:
      Detection and colour Doppler echocardiographic appearance of residual or
      recurrent shunts, the timing of the appearance of recurrent shunts, and the time
      taken for spontaneous resolution of these shunts. RESULTS: Immediate occlusion
      was achieved in 52 patients. At one month 63 patients had complete occlusion and
      after three months the duct was completely occluded in 67 patients. In 27 cases
      small residual shunts were detected on echocardiography 10 minutes after the
      completion of the implantation procedure; 15 of these had resolved by 24 hours
      and 20 had resolved by three months. Recurrent shunts were detected after
      apparent initial complete occlusion in 11 cases 24 hours after coil implantation
      and in two cases one month after the procedure. Six recurrent shunts resolved on
      later follow up. Residual shunts appeared as single jets after implantation of a
      single coil, but up to three separate jets were detected after implantation of
      multiple coils. CONCLUSIONS: Spontaneous resolution of small residual shunts
      occurs in most patients. The recurrence of small shunts after apparent complete
      occlusion suggests that recanalisation of the duct may occur in a small
      percentage of patients up to one month after occlusion. Residual shunts may take
      the form of multiple residual jets that may require implantation of further coils
      to achieve complete duct occlusion.

PMID- 9602652
TI  - Increasing workload and changing referral patterns in paediatric cardiology
      outreach clinics: implications for consultant staffing.
AB  - OBJECTIVE: To assess the workload of, and referral patterns to, paediatric
      cardiology outreach clinics to provide data for future planning. DESIGN:
      Descriptive study of outpatient attendance during 1991 and 1996. SETTING: Five
      district general hospitals with unchanged local demographics and referral
      patterns during the study period. METHODS: Postal, telephone, and on site survey
      of clinic records and case notes. RESULTS: The number of outpatients increased by
      61%, with a consequent increase in the number of clinics held and patients seen
      in each clinic. The number of patients aged between 10 and 15 years doubled.
      CONCLUSION: These data confirm the impression that demands for paediatric
      cardiology services are increasing. The increased need for attendance at outreach
      clinics has inevitable consequences for the clinical, teaching, and research
      activities of specialists in tertiary centres. An increase in the number of
      paediatric cardiologists, or development of local expertise (general
      paediatricians with an interest in cardiology), will be required. Furthermore,
      the increasingly large cohort of older teenagers and young adults with congenital
      heart disease underscores the need for the development of specialist facilities.

PMID- 9602653
TI  - Balloon expandable stents for systemic venous pathway stenosis late after
      Mustard's operation.
AB  - OBJECTIVES: Description and evaluation of current experience with the use of
      balloon expandable stents for the relief of systemic venous pathway stenosis late
      after Mustard's operation. DESIGN: Retrospective observational study of technical
      procedures, angiographic, and haemodynamic findings. PATIENTS: Twenty long term
      survivors of Mustard's operation for transposition of the great arteries (TGA)
      with angiographic evidence of systemic venous pathway narrowing. INTERVENTION:
      Systemic venous pathway stenoses were stented using balloon expandable Palmaz
      stents. RESULTS: Twenty seven stents were deployed across 24 stenoses. Seventeen
      stents were placed in the inferior baffle (16 patients), with an increase in mean
      (range) minimum diameter from 9.6 (4.5-15.9) to 16.5 (11.9-22.2) mm (p = 0.007),
      and a reduction in mean pressure gradient from 3.1 (0-8) to 0.67 (0-3) mm Hg (p =
      0.002). Eight stents were placed in the superior pathways of eight patients, with
      diameters widened from 9.1 (3.5-14.1) to 15.2 (8.7-19.2) mm (p = 0.018), and
      gradients reduced from 6.4 (2-11) to 0.9 (0-2) mm Hg (p = 0.02). Two badly
      deployed stents were safely withdrawn from their intracardiac positions and
      redeployed in the iliac vein. Transvenous pacemaker insertion was facilitated by
      prior stent insertion. CONCLUSIONS: The use of balloon expandable stents for late
      systemic pathway narrowing after Mustard's operation is safe and effective. The
      beneficial effects of stenting are likely to be more durable than those of
      balloon angioplasty alone, but longer term follow up is required.

PMID- 9602654
TI  - Self expandable stents for relief of venous baffle obstruction after the Mustard
      operation.
AB  - OBJECTIVE: Obstruction of the venous pathways after Mustard repair for
      transposition of the great arteries is associated with an increased risk of
      arrhythmia and sudden death. The purpose of this study was to assess the
      effectiveness of the largest (tracheal 22 x 40 mm) Wallstents in treating baffle
      obstructions. DESIGN: Retrospective analysis of patients with stented venous
      pathways. SUBJECTS: Eleven patients with baffle obstruction after Mustard repair
      for transposition of the great arteries. INTERVENTIONS: Stenoses were dilated
      with an 18 or 20 mm balloon. However, recoil was noticed in 11 patients:
      immediately (n = 7) or on repeat angiography (n = 4). Eighteen stents were
      implanted (mean (SD)) 18 (3.3) years postoperatively. After dilatation a tracheal
      Wallstent (11.5 F) was deployed. MAIN OUTCOME MEASURES: Relief of obstruction,
      haemodynamic improvement. RESULTS: In the inferior vena cava, 10 stents were
      deployed in seven baffle obstructions with an increase in diameter from 9.8 (2.4)
      mm to 16.5 (1.4) mm (p < 0.01) and a mean (SD) pressure gradient decrease from
      5.1 (3.6) mm Hg to 1.4 (2.0) mm Hg; in the superior vena cava, eight stents were
      implanted increasing the diameter from 9.1 (3.7) mm to 15.6 (3.8) mm (p < 0.001)
      with a decrease in mean pressure gradient from 5.1 (2.7) mm Hg to 1.9 (1.5) mm
      Hg. No complications were experienced during implantation. No anticoagulation was
      prescribed. During follow up (1.7 (0.6) years; range, 0.9-2.6) no problems were
      noted; five patients were re-catheterised without change in measurements. There
      was no evidence of peal formation in any of the stents. CONCLUSION: It is
      concluded that Wallstents are safe, easy to use, and effective in relieving
      baffle obstruction. Anticoagulation does not seem necessary.

PMID- 9602655
TI  - Procedural and follow up results with a new balloon expandable stent in
      unselected lesions.
AB  - OBJECTIVE: To assess the clinical and angiographic results of the first clinical
      application of a new balloon expandable stent, the NIR stent, characterised by
      high longitudinal flexibility and low profile before expansion, and by high
      radial support and minimal recoil and shortening after expansion. DESIGN: Single
      centre survey of unselected lesions in consecutive patients. SETTING: Tertiary
      referral centre. PATIENTS AND LESIONS: 93 stents of various length (9, 16, and 32
      mm) were implanted in 64 lesions in 41 patients. Twenty lesions (31%) were longer
      than 15 mm, and 17 lesions (27%) were located in vessels with a diameter smaller
      than 2.5 mm. Extreme tortuosity of the proximal vessel was present in 15 lesions
      (23%). All patients were treated with aspirin and ticlopidine. All lesions were
      evaluated before and after treatment by quantitative angiography, and in 47
      lesions (75%) the stent expansion was also controlled by intracoronary
      ultrasound. Clinical follow up was available in all patients and angiographic
      follow up was performed in 53 lesions (84%), at a mean (SD) interval of 5.4 (1.7)
      months. RESULTS: Deployment of the stent failed in two lesions (3%). Minimum
      lumen diameter increased from 1.01 (0.54) mm to 2.94 (0.49) mm, and diameter
      stenosis decreased from 66(15)% to 7(11)%. There was one in-hospital non-Q wave
      myocardial infarction, one sudden death after 40 days, and 17 target lesion
      revascularisations (27%). Angiographic restenosis (> or = 50% diameter stenosis)
      was documented in 19 lesions (36% of all lesions with angiographic follow up),
      with an average residual diameter stenosis of 43(21)% and minimum lumen diameter
      of 1.63 (0.74) mm. Restenosis was more common in vessels with a reference
      diameter < 2.5 mm (45%) and for lesions longer than 15 mm (46%). CONCLUSIONS: The
      NIR stent could be used successfully in most lesions, achieving optimal
      angiographic results with very few in-hospital or subacute cardiac events. The
      angiographic restenosis rate and need for target lesion revascularisation
      remained high in this unfavourable lesion subset, especially in small vessels and
      long lesions.

PMID- 9602656
TI  - Relation between left ventricular function and oxidative stress in patients
      undergoing bypass surgery.
AB  - OBJECTIVE: To determine whether preoperative left ventricular ejection fraction
      (LVEF) is related to the degree of myocardial oxidative stress during bypass
      surgery in man. DESIGN: Observational study. SETTING: Tertiary care centre.
      PATIENTS AND INTERVENTIONS: 31 patients (LVEF range was 20% to 68%) undergoing
      elective coronary bypass surgery with blood cardioplegic reperfusion were
      studied. Arterial and coronary sinus blood was collected before aortic cross
      clamping (T0) and at 0 (T1), 15 (T2), and 30 (T3) minutes after unclamping.
      Transmural left ventricular biopsies were also obtained from 15 patients at T0
      and at T1. MAIN OUTCOME MEASURES: Glutathione and adenine nucleotides were
      measured in myocardial biopsies, while coronary sinus-artery differences for
      glutathione, nucleotides, and products of lipid peroxidation were calculated from
      blood specimens. Creatine kinase (myocardial band; CK-MB) was measured in plasma
      at four and 12 hours after operation. RESULTS: Myocardial glutathione and adenine
      nucleotides were correlated (p < 0.02) with preoperative LVEF both at T0 (r =
      0.909 and 0.672) and T1 (r = 0.603 and 0.605). Oxidised glutathione released from
      the heart during reperfusion was inversely correlated with LVEF (r = -0.448, 
      0.466, and -0461 at T1, T2, and T3, p < 0.01), while reduced glutathione (r =
      0.519 and 0.640 at T1 and T2) and glutathione redox ratio (r = 0.647, 0.714,
      0.645, and 0.702 at T0, T1, T2, and T3) showed a direct correlation (p < 0.01).
      Lipid peroxidation at T1 was negatively related to LVEF (r = -0.492). CK-MB was
      also negatively related to LVEF (r = -0.440 at 4 h and -0.462 at 12 h).
      CONCLUSIONS: The capacity to counterbalance oxidative burst following ischaemia
      and reperfusion appears to be related to the functional ability of the heart.

PMID- 9602657
TI  - Is metabolic syndrome a discrete entity in the general population? Evidence from
      the Caerphilly and Speedwell population studies.
AB  - OBJECTIVE: To examine the clinical and epidemiological utility of the concepts of
      metabolic syndrome and insulin resistance syndrome in two prospective cohort
      studies of white men. METHODS: Men aged 45-63 years were screened for evidence of
      ischaemic heart disease (IHD) between 1979 and 1982 and followed up at regular
      intervals thereafter. Non-fatal coronary events were validated from hospital
      records and fatal coronary events from death certificates. RESULTS: Analysis of
      serum insulin concentrations in non-diabetic individuals measured at entry to the
      study showed no independent contribution to the prediction of subsequent IHD at
      10 year follow up. Blood glucose concentrations, however, showed a small
      independent contribution in the combined cohort in the upper fifth of the
      distribution. Three different models of metabolic syndrome among non-diabetic
      individuals were defined based on tertiles, medians, and clusters. The predictive
      value of each model was assessed using logistic regression before and after
      adjustment for conventional and metabolic risk factors. After adjustment the odds
      were non-significant and close to unity. CONCLUSIONS: This study did not detect
      any complex relation among the five variables defining metabolic syndrome; the
      excess risk seems to be no greater than can be explained by individual effects of
      the defining variables in a multiple logistic model.

PMID- 9602658
TI  - Subpectoral implantation of a cardioverter defibrillator under local anaesthesia.
AB  - OBJECTIVE: To evaluate patient acceptability of submuscular implantation of a
      cardioverter defibrillator (ICD) under local anaesthesia with conscious sedation.
      DESIGN: Retrospective review. Patient acceptability in the second half of the
      study was routinely assessed within 24 hours. SETTING: Regional cardiac centre.
      PATIENTS: 45 consecutive patients with either aborted sudden death or
      haemodynamically unstable ventricular tachycardia were referred for ICD
      implantation. INTERVENTIONS: A subpectoral implantation technique was employed.
      Twelve procedures were performed under general anaesthesia. Thirty three patients
      were sedated with midazolam and diamorphine, and local anaesthesia was achieved
      with bupivicaine. Ventricular fibrillation for defibrillation threshold testing
      was induced by alternating current, T wave shock, or ultrarapid burst pacing.
      Patients were contacted after the procedure to assess acceptability. RESULTS: 32
      patients having implantation under local anaesthesia did not recall the surgical
      procedure. One patient described an awareness of "pushing" as the generator was
      positioned in the pocket. Seven patients said that the procedure was painless but
      recalled a test shock, four describing it as mildly uncomfortable. All 33
      patients stated that they would be willing to have a second implant under local
      anaesthesia. Twelve patients who had the implant performed under general
      anaesthesia had no recollection of the procedure. Mean (SD) total procedure
      duration was significantly longer in those who had general anaesthesia (93 (16) v
      67 (17) minutes; p = 0.0009). CONCLUSIONS: Subpectoral implantation of ICDs may
      be performed safely with patient acceptability under local anaesthesia with
      conscious sedation.

PMID- 9602659
TI  - Prediction of the effectiveness of long-term beta blocker treatment for dilated
      cardiomyopathy by signal averaged electrocardiography.
AB  - OBJECTIVE: To determine whether the effectiveness of long-term beta blocker
      treatment for idiopathic dilated cardiomyopathy can be predicted by signal
      averaged electrocardiography (ECG). PATIENTS: 31 patients with dilated
      cardiomyopathy and without bundle branch block were included in a retrospective
      study and 16 in a prospective study. METHODS: A signal averaged ECG was recorded
      before beta blocker treatment, and three variables were measured from the vector
      magnitude: QRS duration, root mean square voltage for the last 40 ms (RMS40), and
      duration of the terminal low amplitude signals (< 40 microV) (LAS40). In the
      retrospective study, these variables were compared among good responders (showing
      > or = 0.10 increase in ejection fraction 12 months after start of beta blocker
      treatment) and poor responders without such improvement. The validity of the
      signal averaged ECG criteria for prediction of the response to beta blocker
      treatment was examined in the prospective study. RESULTS: In the retrospective
      study, good responders (n = 16) had a shorter QRS duration (mean (SD): 122.9 (11)
      v 138 (14.4) ms, p < 0.005) and LAS40 (33.1 (8.9) v 42.5 (7.8) ms, p < 0.005),
      and a higher RMS40 (31.6 (16.3) v 19.0 (10.3) microV, p < 0.02) than poor
      responders (n = 15). Signal averaged ECG criteria for good response were defined
      as two or more of the following: QRS duration < 130 ms, RMS40 > 20 microV, LAS40
      < 40 ms (sensitivity 81%, specificity 73%). In the prospective study, six of
      seven patients who met these criteria showed a good response to the beta blocker
      treatment, while eight of nine who did not showed a poor response (chi 2 = 6.1, p
      < 0.02). The signal averaged ECG criteria gave a sensitivity of 86% and a
      specificity of 89% for predicting the effectiveness of beta blocker treatment.
      CONCLUSIONS: A signal averaged ECG might be useful in predicting the
      effectiveness of beta blocker treatment for dilated cardiomyopathy.

PMID- 9602660
TI  - A normal electrocardiogram precludes the need for left ventriculography in the
      assessment of coronary artery disease.
AB  - OBJECTIVE: To assess whether a normal electrocardiogram can identify good left
      ventricular function and obviate the need for routine left ventriculography in
      patients undergoing cardiac catheterization for suspected coronary artery
      disease. DESIGN: A prospective study of patients undergoing cardiac
      catheterisation. SETTING: A regional cardiac centre. PATIENTS: The
      electrocardiograms, coronary angiograms, and left ventriculograms of 391
      consecutive patients undergoing investigations for suspected coronary artery
      disease were entered into the study. Patients with arrhythmias and cardiac
      pathologies other than coronary artery disease were excluded. MAIN OUTCOME
      MEASURES: The electrocardiogram was assessed using a 29 point QRS scoring system,
      and classified by two cardiologists and a trainee cardiologist as normal or
      abnormal. Left ventricular function was assessed by digital ventriculography.
      RESULTS: The sensitivity, specificity, and negative predictive value of a QRS
      score of 0 (normal QRS complexes) for discriminating good left ventricular
      function (ejection fraction > or = 50%) were 92.6%, 41.5%, and 97.2%,
      respectively. The figures for a normal electrocardiogram as assessed by a doctor
      were 96.3%, 40.4%, and 98.6% for cardiologist A; 96.3%, 37.4%, and 98.4% for
      cardiologist B; and 94.4%, 49.6%, and 98.2% for the cardiology trainee.
      CONCLUSIONS: If a cardiologist judges the ECG to be normal, left ventriculography
      is unnecessary and a formal QRS score does not improve reliability of this
      clinical judgment. Adopting this strategy would save 30-40,000 Pounds in
      consumables and 65-87 hours of catheter laboratory and staff time for a
      department catheterising 3000 patients with suspected coronary artery disease
      annually.

PMID- 9602662
TI  - Assessment of myocardial perfusion and contractile function by inotropic stress
      Tc-99m sestamibi SPECT imaging and echocardiography for optimal detection of
      multivessel coronary artery disease.
AB  - OBJECTIVE: To assess whether inotropic stress myocardial perfusion imaging,
      echocardiography, or a combination of the two could enhance the detection of
      multivessel disease, over and above clinical and exercise electrocardiographic
      data. DESIGN: 100 consecutive patients investigated by exercise
      electrocardiography and diagnostic coronary arteriography underwent simultaneous
      inotropic stress Tc-99m sestamibi SPECT (MIBI) imaging and echocardiography. MIBI
      imaging and echocardiographic data were analysed using a 12 segment left
      ventricular model, and each segment was ascribed to a particular coronary artery
      territory. The presence of perfusion defects with MIBI imaging or of wall
      thickening abnormality with echocardiography in at least two coronary artery
      territories at peak stress was taken as diagnostic of multivessel disease.
      Arteriographic evidence of > or = 50% stenosis was considered significant.
      RESULTS: 56 patients had multivessel disease. The sensitivity of the combination
      of MIBI imaging and echocardiography for detecting this was greater than either
      MIBI imaging or echocardiography alone (82%, 68%, and 68%, respectively; p =
      0.005). Clinical and exercise electrocardiographic variables gave an R2 value of
      18.2% for predicting multivessel disease. The addition of either MIBI imaging (R2
      = 29.2%; p = 0.002) or echocardiography (R2 = 28.8%; p < 0.001) enhanced the
      detection of multivessel disease, and the inclusion of both had further
      incremental value (R2 = 34.8%; p = 0.003). Age (p = 0.03), MIBI imaging (p =
      0.007), and echocardiography (p = 0.001) were independent predictors of
      multivessel disease. CONCLUSIONS: The assessment of both myocardial perfusion and
      contractile function by simultaneous inotropic stress MIBI imaging and
      echocardiography optimises the non-invasive detection of multivessel disease.

PMID- 9602661
TI  - Segmental wall motion abnormalities alter vulnerability to ventricular ectopic
      beats associated with acute increases in aortic pressure in patients with
      underlying coronary artery disease.
AB  - OBJECTIVE: To evaluate whether patients with coronary artery disease are
      susceptible to pressure related ventricular arrhythmias, and if so to identify
      possible risk factors. DESIGN: Interventional study. METHODS: Metaraminol was
      given to 43 patients undergoing coronary arteriography for ischaemic heart
      disease to increase their aortic pressure, provided their systolic blood pressure
      was < 160 mm Hg and they were in sinus rhythm, without any ventricular ectopic
      activity (or with fewer than six ventricular ectopic beats a minute) during a
      five minute control period. RESULTS: During the metaraminol infusion, systolic
      aortic pressure rose from 131 (15) to 199 (12) mm Hg (mean (SD)). Ventricular
      ectopy appeared (or ventricular ectopic beats increased by > 100%) in 13/43
      patients. Ventricular ectopy was not related to age, sex, presence of
      hypertension, history of myocardial infarction, use of beta blockers, positive
      exercise test, number of vessels diseased, or heart rate change during
      metaraminol infusion. There was a strong relation between the appearance of
      ventricular arrhythmia and segmental wall motion abnormalities: 1/19 (5.3%, 95%
      confidence interval 0.1% to 26.0%) without abnormality; 2/12 (16.7%, 2.1% to
      48.4%) with hypokinesia; and 10/12 (83.3%, 51.6% to 97.1%) with akinesia or
      dyskinesia, chi 2 = 22.7, p < 0.001). Ejection fraction was also a significant
      but not independent risk factor. CONCLUSIONS: Patients with segmental wall motion
      abnormalities are predisposed to ventricular ectopic beats during an increase in
      systolic aortic pressure. This could be explained by associated
      electrophysiological inhomogeneity. The presence of mechanical inhomogeneity, as
      may occur in postinfarction akinesia or dyskinesia, may affect the aortic
      pressure above which ventricular arrhythmias appear.

PMID- 9602664
TI  - Images in cardiology. Onion skin aneurysm of the aortic arch.

PMID- 9602663
TI  - Predictive value of dobutamine echocardiography and positron emission tomography
      in identifying hibernating myocardium in patients with postischaemic heart
      failure.
AB  - OBJECTIVE: To compare the predictive value of dobutamine echocardiography (DE)
      and positron emission tomography (PET) in identifying reversible chronic left
      ventricular (LV) dysfunction (hibernating myocardium) in patients with coronary
      artery disease (CAD) and overt heart failure. PATIENTS: 30 patients (four women)
      with CAD and heart failure undergoing coronary artery bypass grafting (CABG).
      METHODS: Myocardial viability was assessed with DE (5 and 10 micrograms/kg/min)
      and PET with [18F] 2-fluoro-2-deoxy-D-glucose (FDG) under hyperinsulinaemic
      euglycaemic clamp. Regional (echo) and global LV function (MUGA) were assessed at
      baseline and six months after CABG. RESULTS: 192 of the 336 (57%) dysfunctional
      LV segments improved function following CABG (hibernating) and the LV ejection
      fraction (EF) increased from 23(7) to 32(9)% (p < 0.0001) (in 17 patients > 5%).
      DE and PET had similar positive predictive values (68% and 66%) in the
      identification of hibernating myocardium, but DE had a significantly lower
      negative predictive value than PET (54% v 96%; p < 0.0001). A significant linear
      correlation was found between the number of PET viable segments and the changes
      in EF following CABG (r = 0.65; p = 0.0001). Stepwise logistic regression
      identified the number of PET viable segments as an independent predictor of
      improvement in EF > 5%, whereas the number of DE viable segments, the baseline
      LVEF, and wall motion were not. CONCLUSIONS: DE has a higher false negative rate
      than PET in identifying recoverable LV dysfunction in patients with severe
      postischaemic heart failure. The amount of PET viable myocardium correlates with
      the functional outcome following CABG.

PMID- 9602665
TI  - Physiological cardiac reserve: development of a non-invasive method and first
      estimates in man.
AB  - OBJECTIVE: To investigate whether physiological cardiac reserve can be measured
      in man without invasive procedures and whether it is a major determinant of
      exercise capacity. DESIGN: Development of method of measurement and an
      observational study. SETTING: A regional cardiothoracic centre. SUBJECTS: 70
      subjects with a wide range of cardiac function, from heart failure patients to
      athletes. METHODS: Subjects underwent treadmill, symptom limited cardiopulmonary
      exercise tests to measure aerobic exercise capacity (represented by VO2max) and
      cardiac reserve. Cardiac output was measured non-invasively using the CO2
      rebreathing technique. RESULTS: Cardiac power output (CPOmax) at peak exercise
      was found to be significantly related to aerobic capacity: CPOmax (W) = 0.35 +
      1.5 VO2max (1/min), r = 0.87, p < 0.001. It also correlated well with exercise
      duration (r = 0.62, p < 0.001), suggesting that cardiac reserve is a major
      determinant of exercise capacity. In the study, cardiac reserve ranged from 0.27
      to 5.65 W, indicating a 20-fold difference between the most impaired cardiac
      function and that of the fittest subject. CONCLUSIONS: A non-invasive method of
      estimating physiological cardiac reserve was developed. The reserve was found to
      be a major determinant of exercise capacity in a population of normal subjects
      and patients with heart disease. This method may thus be used to provide a
      clearer definition of the extent of cardiac impairment in patients with heart
      failure.

PMID- 9602666
TI  - Left ventricular long axis disturbances as predictors for thallium perfusion
      defects in patients with known peripheral vascular disease.
AB  - OBJECTIVE: To compare resting long axis echocardiography with adenosine thallium
      201 emission tomography in detecting myocardial ischaemic abnormalities in
      patients before peripheral vascular surgery. DESIGN: A prospective and blinded
      preoperative examination of resting left ventricular minor and long axes and
      myocardial perfusion during adenosine vasodilatation using thallium-201 emission
      tomography. SETTING: A tertiary referral centre for cardiac and vascular disease
      equipped with invasive, non-invasive, and surgical facilities. SUBJECTS: 65
      patients (40 men) with significant peripheral vascular disease, mean (SD) age 63
      (10) years, and 21 control subjects of similar age. METHODS: Segments were
      classified as normal, with fixed or reversible defects according to thallium-201
      myocardial perfusion tomography. Systolic long axis abnormalities were either
      reduced excursion and/or abnormal shortening after A2, and diastolic
      abnormalities either delayed onset of lengthening > 80 ms and/or reduced peak
      lengthening rate < 4.5 cm/s. Segmental perfusion defects were compared with the
      equivalent long axes; anteroseptal for septal, inferoseptal for posterior, and
      lateral for left side giving a total of 195 segments. RESULTS: Systolic long axis
      abnormalities predicted fixed thallium defects (sensitivity 86%, specificity 87%,
      positive predictive value 0.78, negative predictive value 0.93, p < 0.001), and
      diastolic abnormalities correlated with reversible perfusion defects (sensitivity
      90%, specificity 85%, positive predictive value 0.72, negative predictive value
      0.95, p < 0.001). Echocardiography characteristics of the true and false positive
      segments were not different in the site or the extent of abnormalities.
      CONCLUSION: Systolic long axis abnormalities predict fixed and diastolic
      reversible thallium perfusion defects in patients with peripheral vascular
      disease. Ventricular long axis may thus have a value as a screening test before
      peripheral vascular surgery as well as providing a means of monitoring myocardial
      perfusion. The high negative predictive values indicate that a negative long axis
      study makes significant perfusion abnormalities very unlikely in patients with
      high pretest probability of coronary artery disease.

PMID- 9602667
TI  - Fibroelastoma: case report and review of the literature.
AB  - A 64 year old woman presented with right hemianaesthesia and was found to have a
      pansystolic apical murmur with systolic and diastolic posture related plops.
      Echocardiography revealed a mobile mass on the mitral valve apparatus that was
      confirmed by magnetic resonance imaging. This was successfully excised and was
      proven on histopathological examination to be a fibroelastoma. Other cases of
      fibroelastoma from the literature are reviewed.

PMID- 9602668
TI  - Bifid T waves induced by isoprenaline in a patient with Brugada syndrome.
AB  - A 41 year old man with incomplete right bundle branch block and persistent coved
      type ST elevation in the right precordial leads during sinus rhythm had an
      episode of syncope while driving. He had never had syncope before and there was
      no family history of sudden cardiac death. Ventricular fibrillation was induced
      during electrophysiological study (EPS) by double extrastimuli applied to the
      right ventricle. Disopyramide was effective in preventing ventricular
      fibrillation during EPS. beta Adrenoceptor stimulation manifested bifid T waves
      and reduced ST segment elevation in right precordial leads. Simultaneously
      recorded monophasic action potential (MAP) duration at 90% repolarisation did not
      change in the right ventricular outflow tract, while it shortened in the left
      ventricular septum. These findings suggest that right precordial bifid T waves
      might result from relatively early repolarisation of the left ventricles.
      Moreover the gradient of action potential duration might explain the mechanism of
      ST segment abnormalities in a patient with Brugada syndrome.

PMID- 9602669
TI  - Images in cardiology. Cardiac papillary fibroelastoma with cerebral and coronary
      embolic events.

PMID- 9602670
TI  - Recanalisation after coil embolisation of persistent ductus arteriosus.
AB  - A 5 year old girl underwent recanalisation after coil embolisation of a
      persistent ductus arteriosus. Recanalisation is uncommon after coil embolisation
      and may be related to shrinkage of the coil, a change in its position, and ductal
      shape.

PMID- 9602671
TI  - Images in cardiology. Pseudoaneurysm of the thoracic aorta presenting with
      angina: a late complication of aortic valve replacement.

PMID- 9602672
TI  - Late onset pulmonary valvar stenosis after arterial switch operation for
      transposition of the great arteries.

PMID- 9602673
TI  - Apoptosis in cardiovascular disease.

PMID- 9602674
TI  - Familial and primary cardiac amyloidosis: echocardiographically similar diseases
      with distinctly different clinical outcomes.

PMID- 9602675
TI  - Helicobacter pylori and coronary artery disease.

PMID- 9602676
TI  - Fool proof fax facilities: a valuable tool in thrombolysis decision making.

PMID- 9602677
TI  - Decentralised anticoagulant care.

PMID- 9602678
TI  - Health economics and clinical pathology.

PMID- 9602679
TI  - Autografting as first line treatment for chronic myeloid leukaemia.
AB  - Interest in autografting for chronic myeloid leukaemia and its clinical relevance
      has revived in recent years. This followed observations that with various
      chemotherapeutic regimens it was possible to achieve, temporarily at least,
      peripheral blood and bone marrow that were Philadelphia negative. Bone marrow or
      peripheral blood progenitor cells could then be harvested and reinfused following
      a high dose procedure, hopefully eliminating any residual disease, and resulting
      in prolonged disease free survival. This ideal has not yet been successfully
      achieved with current strategies. Recent results indicate that eliminating
      residual disease with current chemotherapy is not normally achievable. The use of
      more sensitive technologies such as polymerase chain reaction has revealed
      persistent disease in most if not all apparently Philadelphia negative cases.
      This is confirmed by results where disease relapse occurs following transplant in
      these cases. Despite this, clinically relevant remissions are obtained and
      further trials are indicated. In this review present treatment is discussed and
      future strategies, using novel techniques as an adjunct to current treatment, are
      proposed that might improve on present results or even lead to the elusive goal
      of cure.

PMID- 9602680
TI  - Aetiology, pathogenesis, and pathology of cervical neoplasia.
AB  - Early epidemiological studies of cervical neoplasia suggested a causal relation
      with sexual activity and human papillomaviruses (HPVs) have emerged as prime
      suspects as venerally transmitted carcinogens. HPVs fall into two broad camps:
      low risk types, associated with cervical condylomas and CIN 1; and high risk
      types (mostly 16 and 18), found in 50-80% of CIN 2 and CIN 3 lesions, and 90% of
      cancers. This association with cancer is very strong, with odds ratios of > 15
      (often much higher) in case-control studies that are methodologically sound. An
      infrequently detected third group of intermediate risk type HPVs is associated
      with all grades of CIN and occasionally with cancers. HPVs have also been
      detected in a wide range of asymptomatic controls, indicating that other events
      are required for development of neoplasia such as viral persistence and/or
      altered expression of viral genes, often following integration of the viral
      genome. This leaves the two major viral oncogenes, E6 and E7, directly coupled to
      viral enhancers and promoters, allowing their continued expression after
      integration. High risk HPV E7 proteins bind and inactivate the Rb protein,
      whereas E6 proteins bind p53 and direct its rapid degradation. A range of
      putative cofactors has been implicated in progression: HLA type,
      immunosuppression, sex steroid hormones, and smoking; most of these cofactors
      appear to influence progression to CIN 3. The natural history includes
      progression to CIN 3 in 10% of CIN 1 and 20% of CIN 2 cases, whereas at least 12%
      of CIN 3 cases progress to invasive carcinoma. Cervical glandular intraepithelial
      neoplasia (CGIN) often coexists with squamous CIN, and the premalignant potential
      of high grade CGIN is not in doubt, but the natural history of low grade CGIN
      remains uncertain. A high proportion of CGIN lesions and adenocarcinomas are HPV
      positive, and HPV18 has been implicated more in glandular than in squamous
      lesions. A strong clinical case for the application of HPV typing of cells
      recovered from cervical scrapes can be made; however, a rigorous cost-benefit
      analysis of introducing HPV typing into the cervical screening programme is
      required. Prophylactic and therapeutic HPV vaccines are under development. This
      article reviews the aetiology, pathogenesis, and pathology of cervical neoplasia,
      emphasising the role of HPVs.

PMID- 9602681
TI  - Application of the principle of marginal analysis to sampling practice using
      prostatic chippings as a model.
AB  - AIMS: To demonstrate an application of health economic principles in
      histopathology by using the sampling of transurethral resections of prostate
      specimens. By demonstrating how marginal costs are calculated the aim is to
      illustrate that the potential opportunity cost of sampling entire specimens is
      much greater than would be anticipated by taking average cost, or the cost of
      producing a histological section alone. METHOD: A mathematical model is used with
      data obtained from the Aberdeen pathology department files and published
      estimates of the likely percentage of cancerous chippings in each specimen.
      RESULTS: The average cost of each cancer detected remains low, between 47 Pounds
      and 151 Pounds, in all the scenarios examined. However, the marginal costs can
      become high, exceeding 10,000 Pounds in larger specimens, if all the chippings
      are processed. CONCLUSIONS: This study demonstrates that there are potential
      opportunity cost penalties to histopathological services associated with sampling
      strategies. Although the results are derived from a hypothetical mathematical
      model using local data that applies only to histopathology, the method could be
      widely applied. The principles of marginal analysis should be performed by
      multidisciplinary teams and include outcomes as well as a broader range of costs,
      including those that arise subsequent to diagnosis.

PMID- 9602682
TI  - Diagnosis of early acute renal allograft rejection by evaluation of multiple
      histological features using a Bayesian belief network.
AB  - BACKGROUND AND AIMS: The development of the Banff classification of renal
      transplant pathology has allowed the standardisation of approaches to transplant
      biopsy histology and reduced interobserver and interdepartmental variation. The
      usefulness of the Banff classification in the diagnosis of acute rejection has
      previously been tested by sending sections from 21 "difficult" biopsies to almost
      all of the renal transplant pathologists in the UK. Although the Banff
      classification improved reproducibility, the accuracy of diagnosis of early acute
      rejection was unchanged from the "conventional" approach. Perhaps this is because
      in making a diagnosis of acute rejection, the Banff classification uses only two
      features: tubulitis and intimal arteritis. To include more features on a
      systematic basis would be laborious for a human observer. Therefore, a Bayesian
      belief network was developed for this task. METHODS: The network was initialised
      with observations from 110 transplant biopsies. Its performance was then tested
      on 21 biopsies that had been seen by 37 different renal transplant pathologists
      in an earlier study. These biopsies had been selected to represent histologically
      difficult problems but, in retrospect, they all had clear diagnoses of rejection
      or non-rejection on clinical grounds. RESULTS: Using the Bayesian belief network,
      a relatively inexperienced pathologist made 19 of 21 correct diagnoses, better
      than had been achieved by any of the pathologists who had seen the same sections
      previously (17 of 21), and considerably better than the average proportion of
      correct diagnoses provided by all 37 renal transplant pathologists (65%).
      Application of the system by a second pathologist produced a tendency to
      overdiagnosis of acute rejection, illustrating the consequences of interobserver
      variation. CONCLUSIONS: In the diagnosis of acute rejection, further useful
      information can be extracted from features that are currently not considered in
      the Banff classification. Integration of data by a computer can give a more
      reliable diagnosis of early acute rejection, but routine application will require
      the development of a more sophisticated system that can also accommodate clinical
      data, perhaps one that can continue to "learn" as more data are entered.

PMID- 9602683
TI  - Immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal
      cortex with a monoclonal antibody against alpha inhibin.
AB  - AIMS: To investigate the immunohisto-chemical staining of normal, hyperplastic,
      and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin.
      Also, to determine whether immunostaining with this antibody is useful in
      differentiating between adrenal cortical neoplasms and other tumours involving
      the adrenal gland that might mimic them. METHODS: Normal adrenal tissue (n = 20)
      and specimens from cases of adrenal hyperplasia (n = 13), adrenal cortical
      adenoma (n = 15), adrenal cortical carcinoma (n = 4), phaeochromocytoma (n = 8),
      and adrenal metastatic tumour (n = 7) were stained with a monoclonal antibody
      against the alpha subunit of human inhibin. RESULTS: Positive staining with the
      anti-alpha inhibin monoclonal antibody was seen in all normal adrenal glands.
      Immunoreactivity was largely confined to the inner cell layers of the adrenal
      cortex, with no staining of the adrenal medulla. All hyperplastic adrenal glands
      and adrenal cortical adenomas and carcinomas were also immunoreactive. The other
      tumours studied were negative. CONCLUSIONS: There is consistent immunoreactivity
      with the anti-alpha inhibin monoclonal antibody in normal adrenal cortex and in
      hyperplastic and neoplastic adrenal cortical lesions. In the normal adrenal
      cortex, positive staining is mainly confined to the zona reticularis. Other
      neoplasms involving the adrenal gland are negative. Immunohistochemical staining
      with anti-alpha inhibin monoclonal antibody, performed as part of a panel, may
      prove to be of value in the distinction between adrenal cortical carcinoma and
      phaeochromocytoma or metastatic tumour.

PMID- 9602684
TI  - Age related somatic mitochondrial DNA deletions in bone.
AB  - BACKGROUND: It has been suggested that the accumulation of damage to
      mitochondrial DNA is a major cause of age related, degenerative disease. Aging is
      known to cause bone loss leading to a fall in bone mineral density and disruption
      of bone microarchitecture. However, despite the evidence of age related bone
      loss, no attempt has been made to detect specific deletions of mitochondrial DNA
      in the bone of aged individuals. AIMS: To detect bone specific, age related
      deletions in mitochondrial DNA. METHOD: Blood leucocytes and bone biopsies from
      patients who had undergone orthopaedic surgery were used as a source of
      mitochondrial DNA and screened for deletions using the polymerase chain reaction.
      RESULTS: Although no deletions were detected in the blood mitochondrial DNA,
      specific deletions in bone mitochondrial DNA were found in three of five elderly
      subjects. CONCLUSION: The findings of this study suggest that there could be a
      link between mitochondrial DNA deletions and free radical induced apoptosis of
      bone cells in the development of age related bone loss.

PMID- 9602685
TI  - Endometrial leucocytes: expression of steroid hormone receptors.
AB  - BACKGROUND: Stromal leucocyte populations in human endometrium comprise T cells,
      macrophages, and phenotypically unusual endometrial granulated lymphocytes. Their
      proportions vary during the menstrual cycle and, in particular, endometrial
      granulated lymphocytes increase in number in the late secretory phase. The
      stimulus responsible for these cyclical changes is unknown but it is likely that
      the steroid hormones oestrogen and progesterone play a role. AIMS: To define
      further the expression of steroid hormone receptors by leucocytes in non-pregnant
      and pregnant human endometrium. METHODS: Frozen and paraffin wax embedded
      sections of endometrium from non-pregnant women and early pregnancy decidua were
      labelled using single and double immunohistochemical techniques with monoclonal
      antibodies directed against oestrogen and progesterone receptors and various
      leucocyte subpopulations. RESULTS: Despite the prominence of CD56 positive
      endometrial granulated lymphocytes in late secretory phase endometrium and early
      pregnancy decidua, double immunohistochemical labelling showed no evidence of
      expression of either progesterone or oestrogen receptors by these cells or other
      endometrial leucocyte populations. CONCLUSIONS: Rather than acting directly,
      steroid hormones are likely to influence endometrial leucocyte populations
      indirectly via products of endometrial stromal or epithelial cells that express
      steroid hormone receptors.

PMID- 9602686
TI  - Assessment of invasion frequencies of cultured HEp-2 cells by clinical isolates
      of Helicobacter pylori using an acridine orange assay.
AB  - AIMS: Recent studies suggest that Helicobacter pylori is an invasive
      enteropathogen. However, the efficiency with which this pathogen invades
      mammalian cells remains unknown. Therefore, this study was designed to
      investigate the invasion frequencies of HEp-2 cells by clinical strains of H
      pylori. METHODS: An acridine orange assay and cultured HEp-2 cell monolayers were
      used to determine the HEp-2 cell penetration frequencies of 17 clinical isolates
      and one American Type Culture Collection (ATCC) strain of H pylori, and single
      clinical strains of Yersinia enterocolitica, Shigella flexneri, and a non
      invasive ATCC Escherichia coli strain. RESULTS: The acridine orange assay
      demonstrated that invasion frequencies of HEp-2 cells by all H pylori isolates
      were significant and, in most instances, exceeded those for the S flexneri strain
      and equalled those for the Y enterocolitica strain. The assay also showed that
      internalised H pylori organisms remained viable for at least six hours, the
      maximum time that bacteria and HEp-2 cells were co-incubated. CONCLUSIONS: These
      results may have important implications for treatment and prevention strategies
      for this gastric pathogen. Furthermore, the acridine orange assay may be useful
      for assessing, in vitro, the ability of conventional and newer antibiotics, alone
      or in combination, to kill intracellular H pylori organisms.

PMID- 9602687
TI  - Differential expression of CD44v6 in metastases of intestinal and diffuse types
      of gastric carcinoma.
AB  - AIMS: To assess whether standard and variant isoforms of CD44 (CD44s, CD44v5, and
      CD44v6) have a differential expression profile in early versus advanced gastric
      adenocarcinoma of the diffuse and intestinal types and their metastases. METHODS:
      Immunohistochemical expression of CD44s, CD44v5, and CD44v6 was evaluated in 14
      early gastric cancers (nine intestinal and five diffuse) and 37 advanced
      adenocarcinomas (21 intestinal and 16 diffuse) as well as in 18 cases of
      perigastric lymph node metastasis. Ten normal and five metaplastic gastric mucosa
      samples were also included in the study. RESULTS: Although no significant
      association was found between the degree of invasion and the CD44 expression
      profile, CD44v6 positivity was detected more frequently in metastases of
      intestinal-type carcinomas (66%) than in metastases of diffuse-type neoplasms
      (11%) (p < 0.05). Weak CD44s, CD44v5, and CD44v6 expression was observed focally
      in both normal and metaplastic gastric mucosa samples. CONCLUSIONS: These data
      suggest that CD44v6 expression may be involved in the production of lymph node
      metastases in intestinal-type gastric carcinoma but not in the diffuse-type
      disease, the metastatic potential of which is most likely unrelated to the CD44
      family of adhesion molecules.

PMID- 9602688
TI  - Chronic cryptosporidiosis in patients with AIDS: stable remission and possible
      eradication after long-term, low dose azithromycin.
AB  - AIMS: To investigate the effectiveness of long term, low dose azithromycin
      treatment for chronic cryptosporidiosis in patients with AIDS. METHODS:
      Azithromycin was administered as initial daily treatment to 13 patients with
      AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received
      1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days.
      Nine of the 13 patients were also given low dose maintenance treatment with
      different schedules of azithromycin for 30 to 360 days (mean 129). Patients were
      monitored, during and after treatment, for parasite shedding in stool and for
      daily stool frequency and body weight. All but one patient had severe
      immunodeficiency. RESULTS: Long term, low dose maintenance treatment was
      associated with major clinical and parasitological benefits: there was probable
      eradication of infection in 2 patients, and 7 patients showed a complete response
      with persistent high decrease (5 patients) or clearance (2 patients) of parasite
      in stool. The drug was well tolerated, and there was no relapse either during
      treatment or during follow up (up to 21 months). These results were more
      impressive than those observed after the short term initial course of
      azithromycin, which was unable at any tested dose to achieve parasite clearance
      in stool (except in the patient with less advanced immunodeficiency) or to
      prevent relapse in 3 patients who discontinued treatment. Reversible side effects
      occurred with the 1500 mg daily dose. CONCLUSIONS: Long term, low dose
      azithromycin is well tolerated and may induce stable remission of chronic
      cryptosporidiosis in patients with AIDS. It may lead to probable eradication of
      the infection in some patients, even those with severe immunodeficiency.

PMID- 9602689
TI  - Evaluation of immunoassays for the detection and typing of PCR amplified human
      papillomavirus DNA.
AB  - AIMS: To evaluate different hybridisation techniques to detect and type human
      papillomavirus (HPV) DNAs amplified by consensus primer polymerase chain reaction
      (PCR) in biopsy and cytological specimens. METHODS: A hybrid capture-immunoassay
      in microtitre wells was performed to detect HPV sequences amplified by PCR and
      typed by specific oligoprobes. Consensus primers were used to amplify a sequence
      within the L1 open reading frame, and direct digoxigenin labelling of amplified
      products was performed during the amplification reaction. The amplified product
      was separately hybridised with six biotinylated type specific probes (HPV6, 11,
      16, 18, 31, and 33); hybrids were then captured into streptavidin coated
      microtitre wells and detected by a spectrophotometer as an ELISA using
      antidigoxigenin Fab fragment labelled with peroxidase and a colorimetric
      substrate. The results were compared with the dot-blot immunoassay used to detect
      and type PCR amplified HPV DNA sequences. Consensus primers were used to generate
      the same unlabelled PCR product; digoxigenin labelled type specific probes for
      HPV6, 11, 16, 18, 31, and 33 were used and hybrids visualised by colorimetric
      immunoenzymatic reaction. Thirty nine biopsy specimens and 31 cytological samples
      were tested by the PCR-ELISA and by standard PCR followed by dot-blot
      hybridisation. RESULTS: The PCR-ELISA proved to be more sensitive than standard
      PCR with dot-blot hybridisation typing. All samples positive for HPV-DNA in
      standard PCR with dot-blot hybridisation method were confirmed positive by the
      PCR-ELISA assay; however, seven samples were positive only by PCR-ELISA.
      CONCLUSIONS: The PCR-ELISA assay, which can be performed in one day, is easily
      standardised and therefore seems to be a practical, sensitive, and reliable
      diagnostic tool for the detection and typing of HPV genomes in biopsy and in
      cytological specimens in the routine diagnostic laboratory.

PMID- 9602690
TI  - Use of PCR in resolving diagnostic difficulties potentially caused by genetic
      variation of hepatitis B virus.
AB  - AIMS: To assess the relevance of genetic variants of hepatitis B virus (HBV) and
      to demonstrate the usefulness of the polymerase chain reaction (PCR) in cases of
      HBV diagnostic difficulty. METHODS: Five serum samples from patients that
      presented diagnostic difficulty in routine laboratories were sent to a research
      laboratory for PCR, and if appropriate, S gene sequencing, in vitro expression,
      and antigenic analysis. RESULTS: The demonstration of HBV in serum by PCR allowed
      a definitive diagnosis of current infection. One serum sample with poor
      reactivity in a diagnostic assay had a minor hepatitis B surface antigen (HBsAg)
      variant and another with very poor reactivity had multiple variants of HBsAg.
      Transient HBsAg reactivity was observed in a recently vaccinated patient. A
      hepatitis Be antigen (HBeAg) false positive reaction was noted in a patient from
      a well defined risk group for HBV. One patient who was strongly HBsAg/HBeAg
      positive, but anti-hepatitis B core antibody negative, was viraemic. CONCLUSIONS:
      PCR may become the gold standard for the diagnosis of current HBV infection. HBV
      variants are responsible for a proportion of diagnostically difficult cases.
      Modification of commercial assays is necessary to increase the sensitivity of
      detection of such variants.

PMID- 9602691
TI  - Differentiation between actinic reticuloid and cutaneous T cell lymphoma by T
      cell receptor gamma gene rearrangement analysis and immunophenotyping.
AB  - AIMS: Differentiation between actinic reticuloid and cutaneous T cell lymphoma
      can be extremely difficult. Demonstration of clonal T cell receptor (TCR) gene
      rearrangements has been suggested as a potential diagnostic criterion, but the
      results obtained thus far have been conflicting. This study investigated whether
      TCR gamma gene rearrangement analysis, using polymerase chain reaction (PCR) in
      combination with denaturing gradient gel electrophoresis (DGGE) and
      immunohistochemistry, can serve as a diagnostic criterion. METHODS: PCR/DGGE was
      performed on skin, peripheral blood mononuclear cells, and/or lymph nodes of
      seven patients with actinic reticuloid, 11 patients with Sezary syndrome, and 15
      patients with a benign form of erythroderma. The results of PCR/DGGE and Southern
      blot analysis of TCR beta gene rearrangements were compared. In addition, CD4:CD8
      ratios in skin and peripheral blood samples were investigated. RESULTS: Clonal T
      cell populations were detected in 19 of 21 samples obtained from patients with
      Sezary syndrome but were not detected in any of the 12 samples from patients with
      actinic reticuloid. Clonal T cells were detected in the peripheral blood of only
      one of 15 patients with a benign form of erythroderma. PCR/DGGE and Southern blot
      analysis gave concordant results in 28 of 29 samples. Immunophenotypic analysis
      demonstrated increased proportions of CD8+ T cells in skin (seven of seven cases)
      and peripheral blood (four of seven cases) of patients with actinic reticuloid.
      CONCLUSION: The results of this study demonstrate that gene rearrangement
      analysis, in combination with immunohistochemistry, may be an important adjunct
      in differentiating between actinic reticuloid and cutaneous T cell lymphoma. In
      patients suspected of having actinic reticuloid, application of both techniques
      is recommended.

PMID- 9602692
TI  - p21WAF1/CIP1 expression in gestational trophoblastic disease: correlation with
      clinicopathological parameters, and Ki67 and p53 gene expression.
AB  - BACKGROUND: The p21WAF1/CIP1 gene mediates growth arrest by inhibiting G1 cyclin
      dependent kinases and has been considered as a downstream effector of the tumour
      suppressor gene p53. AIM: To analyse the role of p21WAF1/CIP1 in gestational
      trophoblastic disease. METHODS: The immunohistochemical expression of
      p21WAF1/CIP1 gene was measured in 33 placentas, 28 partial hydatidiform moles, 54
      complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded
      tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1)
      immunoreactivity as well as clinical progress. RESULTS: p21WAF1/CIP1
      immunoreactivity was found predominantly in the nuclei of the
      syncytiotrophoblasts. p21WAF1/CIP1 protein expression correlated with gestational
      age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89).
      Complete hydatidiform moles and choriocarcinomas had a significantly higher
      p21WAF1/CIP1 expression compared with normal placentas and partial hydatidiform
      moles (p < 0.001); there was no difference between placentas and partial
      hydatidiform moles. No correlation between p21WAF1/CIP1 expression and either the
      proliferation (Ki67) index (p = 0.34) or p53 protein accumulation (p = 0.68) was
      demonstrated. There was no significant difference (p > 0.05) in p21WAF1/CIP1
      expression between the 17 patients who developed persistent gestational
      trophoblastic disease and those who did not. CONCLUSIONS: This study suggests
      that p21WAF1/CIP1 expression in trophoblastic disease may be induced by a p53
      independent pathway. The proliferative activity of gestational trophoblastic
      diseases might not be determined solely by the control of the cell cycle operated
      by p21WAF1/CIP1. p21WAF1/CIP1 expression is not an accurate prognostic indicator
      of gestational trophoblastic disease.

PMID- 9602693
TI  - Postmortem examination of the lungs: a preservation technique for opening the
      bronchi and pulmonary arteries individually without transection problems.
AB  - The classic methods of examining both the pulmonary arteries and bronchi
      postmortem partly destroy the anatomy of one of these systems. A technique is
      described whereby the bronchi and pulmonary arteries are dissected and preserved.
      The principal difference of this technique is that most of the upper lobe
      vasculature is opened from the hilum. The exception to this is the lingula, which
      because it is the embryological homologue of the right middle lobe should be
      treated in the same way--that is, with the vessels opened from the pleural side
      and the bronchi from the hilum. One general practical point is that there is a
      great variation in the number of pulmonary arterial branches in each lobe,
      particularly in the upper lobes, and especially in the left upper lobe.
      Furthermore, there is some variation in the local anatomic relations of the
      vessels and bronchi and on occasion the technique will not work as described and
      will require some modification. However, most of the time this technique should
      allow the pathologist to preserve the anatomy of the bronchial tree and pulmonary
      arteries for better demonstration and photographic purposes when the need arises.

PMID- 9602694
TI  - How many lymph nodes to stage colorectal carcinoma?
AB  - This study aimed to establish the number of cassettes that should be filled with
      lymph nodes to stage a colorectal carcinoma as Dukes's stage C. The records from
      the Oxford Colorectal Cancer database of all patients diagnosed with Dukes's
      stage C cancer from late 1988 to early 1993 were reviewed. Each slide of lymph
      nodes was examined to determine how many slides needed to be looked at to find
      the first positive lymph node. The resected specimens were not fat cleared but
      dissected manually in a routine fashion. One hundred and eight slides were
      retrieved. The mean total lymph node harvest was 8.44 for each patient. Ninety
      eight patients (90.7%) had positive lymph nodes on the first slide with an
      average of 3.42 lymph nodes on each slide, of which a mean of 1.82 were positive.
      For nine patients, two slides were required to make a diagnosis of lymph node
      involvement, and for one patient the first three slides needed inspection to
      establish Dukes's stage C. In conclusion, using a routine technique to obtain
      lymph nodes from colorectal cancer specimens 99% of Dukes's stage C colorectal
      carcinoma can be found by filling two cassettes with lymph nodes.

PMID- 9602695
TI  - Increased expression of proliferating cell nuclear antigen in autoimmune
      hepatitis in a patient with raised serum concentration of CA19-9.
AB  - A 52 year old woman had autoimmune hepatitis and an increased concentration of
      serum carbohydrate antigen 19-9 (CA19-9). The origin of the raised CA19-9 was
      studied using immunohistochemistry. Liver biopsy section showed chronic active
      hepatitis with large numbers of proliferated bile ductules. Immunohistochemical
      analysis revealed that the proliferated bile ductule cells were positive for
      proliferating cell nuclear antigen (PCNA) and for CA19-9. It is speculated that
      the raised serum CA19-9 concentration was derived from proliferated bile ductule
      cells and these cells, which are positive for PCNA, may be able to produce high
      concentrations of CA19-9.

PMID- 9602696
TI  - A case of systemic pseudo-pseudoxanthoma elasticum with diverse symptomatology
      caused by long-term penicillamine use.
AB  - A 47 year old man presented with a two year history of increasing cervical
      dysphagia, dyspnoea, and cutaneous signs. He had been diagnosed 27 years
      previously with Wilson's disease and was treated with penicillamine (1.5 g
      daily). Systemic abnormality of elastic fibres was confirmed by light and
      electron microscopy following biopsy of skin, lung, oesophageal muscle, gum,
      pharyngeal tissue, and cervical connective tissue. Dysphagia was relieved by
      cricopharyngeal myotomy. Substitution of trientene dihydrochloride for
      penicillamine relieved cutaneous and systemic manifestations. This is possibly
      the first case demonstrating an association between prolonged penicillamine use
      and biopsy proved systemic pseudo-pseudoxanthoma elasticum. The presenting
      symptoms may have resulted from the abnormal numbers and properties of elastic
      fibres, and the changes were caused by penicillamine use, rather than by
      idiopathic, inherited pseudoxanthoma elasticum.

PMID- 9602697
TI  - Intravascular synovial sarcoma.
AB  - A case of intravascular biphasic synovial sarcoma arising from the wall of the
      left femoral vein in a 34 year old woman is described. This is the third case of
      an intravascular synovial sarcoma known to be reported in the medical literature.
      The two previous cases arose from the left femoral vein and inferior vena cava in
      women of 34 and 31 years old, respectively. A characteristic clinical pattern
      appears to be emerging--that is, location in large veins of the lower extremity
      and trunk in young adult females. Synovial sarcoma must be considered in the
      differential diagnosis of intravascular "tumours".

PMID- 9602698
TI  - Laboratory identification of Streptococcus milleri.

PMID- 9602699
TI  - The dysplastic naevus.

PMID- 9602700
TI  - Tumoural vascularity as a prognostic factor in cancer patients: the evidence
      continues to grow.
AB  - Accurate prognostic indicators would help in identifying patients at high risk
      for recurrence and death. Recent and previous studies indicate that intratumoural
      microvessel density (iMVD) of invasive breast carcinoma (a measure of tumour
      angiogenesis) is associated with aggressive tumour growth; iMVD may thus be a
      valuable prognostic indicator. Moreover, the bulk of accumulating data indicates
      that microvessel density in the area of most intense neovascularization in
      invasive breast carcinoma is an independent, significant and accurate prognostic
      indicator in predicting poorer survival. Such an indicator would be useful in the
      selection of high-risk patients with breast carcinoma for systemic adjuvant
      therapy.

PMID- 9602701
TI  - Glomerular pathology: recent advances.
AB  - The last decade has seen significant advances in the fields of cellular and
      molecular biology and pathology. These have contributed to our understanding of
      the mechanisms of glomerular disease and indicate possible novel approaches to
      therapy. This review discusses recent insights into the pathogenesis of
      glomerular disease, with consideration of the roles of intrinsic glomerular
      cells, infiltrating inflammatory cells, circulating permeability factors, and
      antibodies, and recent advances in the molecular pathology of the glomerular
      basement membrane. Changes in the perception of some well-established glomerular
      entities such as focal segmental glomerulosclerosis are considered. In addition,
      a number of newly-recognized specific glomerulopathies including collapsing
      glomerulopathy, fibrillary and immunotactoid glomerulopathy, fibronectin
      glomerulopathy, and collagenofibrotic glomerulopathy are briefly reviewed.

PMID- 9602702
TI  - Angiogenesis as a prognostic marker in breast carcinoma with conventional
      adjuvant chemotherapy: a multiparametric and immunohistochemical analysis.
AB  - It has now been clearly established that quantitative immunohistochemical methods
      applied to tumour angiogenesis under suitable quality control conditions are a
      powerful prognostic tool for use in the initial assessment of breast carcinomas.
      Appropriate parameters for predicting the aggressiveness of tumours and their
      sensitivity to treatment are, however, still required. To determine whether the
      microvessel count (MVC) may serve to predict the chemotherapeutic response, a
      retrospective study was carried out on a series of 162 patients with breast
      carcinoma, who were all treated with the same standard adjuvant chemotherapy.
      Angiogenesis was assessed by performing CD31 immunostaining and MVC per mm2.
      Several other factors such as P53, ERBB2, BCL2, and Ki67 were also measured, and
      their prognostic value was compared with that of the MVC. The MVC was not found
      to be correlated with any of the other prognostic parameters, but turned out to
      be of great prognostic value whatever the threshold value chosen, which suggests
      that it is continuously valid at all levels. The median value of the MVC (43.5
      per mm2) divided this series into two significantly different prognostic
      categories, in terms of both disease-free survival (P = 0.0002) and overall
      survival (P = 0.037). Univariate analysis showed that most of the parameters
      analysed were of prognostic value regarding the disease-free survival, namely
      grade (P = 0.029), mitotic index (P = 0.049), size (P = 0.015), oestrogen
      receptors (P = 0.022), progesterone receptors (P = 0.018), P53 (P = 0.0045),
      ERBB2 (P = 0.046), and Ki67 (P = 0.0008). As regards overall survival, grade and
      ERBB2 showed a loss of prognostic value. In multivariate analysis on disease-free
      survival, the MVC was the most accurate prognostic factor (RR = 2.64), followed
      by Ki67 (RR = 2.06) and P53 (RR = 1.69). With respect to overall survival, the
      MVC ranked third among the prognostic parameters analysed. Standard chemotherapy
      did not reduce the high prognostic value of the MVC performed on tumour
      angiogenesis. This suggests that the MVC may predict the degree of resistance to
      chemotherapy. Patients with high levels of angiogenesis, particularly node
      negative patients, might therefore be able to benefit from adjuvant therapy of
      another kind.

PMID- 9602703
TI  - An improved procedure to quantify tumour vascularity using true colour image
      analysis. Comparison with the manual hot-spot procedure in a human melanoma
      xenograft model.
AB  - In a number of recent papers, the degree of tumour vascularization has been
      described as a promising new prognostic factor. Methods for the assessment of
      vascular density involve immunohistochemical staining of the vasculature,
      followed by counting the number of vessel profiles in the angiogenic hot spot.
      One of the problems of this procedure is the selection of the angiogenic hot
      spot, which has been described as being subject to inter-observer variation. In
      this study, the value of true colour image analysis in reducing inter-observer
      variation has been assessed. Highly (MV3) and poorly (M14) vascularized human
      melanoma xenografts were used to evaluate the image analysis procedure, and the
      image analysis results were compared with results from the conventional manual
      hot-spot procedure. Assessment by image analysis was performed on measurement
      fields covering the entire tumour tissue specimens rather than on a single hot
      spot field. Also, by selecting the most densely vascularized area from all fields
      assessed by the semi-automatic procedure, it was possible to objectify the hot
      spot selection (automated hot-spot procedure). Manual assessment showed a good
      correlation between two independent observers for MV3 xenografts (r = 0.74, P =
      0.014), but a poor correlation for M14 xenographs (r = 0.4, P > 0.05). Automated
      assessment by different operators showed good correlations for both MV3
      xenografts (r = 0.99, P < 0.001) and M14 xenografts (r = 0.80, P = 0.006). It is
      concluded that although both manual vessel counting and semi-automated image
      analysis can differentiate between the level of vascularization in the two types
      of xenograft (P < 0.001 for both methods), the automated method is favourable in
      that it showed no significant inter-observer effects. In M14 xenografts, the
      manual hot-spot vessel densities did not correlate well with the automated hot
      spot densities (r = 0.27, P > 0.05), indicating that selection of angiogenic hot
      spots in this tumour type is indeed subject to observer bias. The automated hot
      spot vessel densities were a reliable indicator of overall tumour vessel density
      in both tumour types. Image analysis allows analysis of vessel subclasses based
      on morphological criteria such as vessel profile area or diameter. In the model
      system used, the discrimination between MV3 and M14 xenografts was further
      enhanced by selectively examining vessels with diameters between 6 and 9 microns
      (P < 0.0005). In conclusion, image analysis appears to offer an objective and
      more reproducible method to quantify tumour vascularity than manual counting of
      vessel profiles in the hot spot. Analysis of subclasses of vessels may further
      enhance the value of vessel density measurements in discriminating between tumour
      types differing in biological behaviour.

PMID- 9602704
TI  - Clonal overexpression of metallothionein is induced by somatic mutation in
      morphologically normal colonic mucosa.
AB  - Metallothionein (MT) overexpression occurs frequently in human tumours but the
      underlying mechanism is unknown. Morphologically normal-appearing mucosa from
      human colorectal carcinoma resection specimens and of the colons of ageing
      laboratory mice contains scattered single crypts whose cells show uniformly
      increased MT immunostaining, suggesting that MT overexpression arises directly
      from random crypt stem cell somatic mutation, followed by colonization of the
      clonal unit by the mutated progeny. This hypothesis has now been tested by
      quantifying the frequency of immunocytochemically detectable monocryptal
      colorectal MT overexpression, 5 and 30 days after injection of 8-week-old mice
      with a single dose of the mutagen dimethylhydrazine (DMH, 30 mg/kg subcutaneous).
      Otherwise normal-appearing MT-positive crypts were recorded as either wholly or
      partially involved by the overexpressing phenotype. Five days after DMH
      injection, the median frequency of partially involved MT-positive crypts was 11.7
      x 10(-4), declining significantly to 1.8 x 10(-4) at 30 days (Mann-Whitney U, P <
      0.01). In contrast, the median frequency of wholly involved crypts was 0.2 x 10(
      4) at 5 days, increasing significantly (P < 0.005) to 12.9 x 10(-4) at 30 days.
      The frequency of MT-positive crypts and the time course of evolution of partially
      involved to wholly involved forms were similar to those described for mutation
      induced crypt-restricted loss of glucose-6-phosphate dehydrogenase activity in
      mice treated with an identical DMH regimen. The findings indicate that cellular
      MT overexpression can occur as a direct consequence of somatic mutation, either
      cis-activating mutation(s) of the MT gene itself, or trans-activating mutation(s)
      of other genes involved in controlling MT expression. This is likely to be an
      important mechanism underlying MT overexpression in neoplasia. Such mutation
      induced aberrant MT expression may be involved in the acquisition of selective
      cellular growth of survival advantage during tumour progression.

PMID- 9602705
TI  - A comparison of the genetic pathways involved in the pathogenesis of three types
      of colorectal cancer.
AB  - Patterns of allele loss (loss of heterozygosity, LOH) have been studied in order
      to investigate the genetic pathways involved in the pathogenesis of three types
      of colorectal cancer (CRC): sporadic CRC without replication errors (RER-) (32
      cases); sporadic RER+ CRC (23 cases); and ulcerative colitis-associated CRC
      (UCACRC) (16 cases). Each tumour was assessed for allele loss at ten
      microsatellite markers which map close to known or putative tumour-suppressor
      genes: APC (5q21-q22); DCC (18q21.1); 1p35-p36; p16 (9p21); 22q; 8p; E-cadherin
      (16q22.1); beta-catenin (3p22-p21.3); RB1 (13q14.1-q14.2); and HLA. Overall, high
      frequencies of allele loss (> 30 per cent) were found near DCC (42 per cent), p16
      (38 per cent), 22q (37 per cent), 1p35-p36 (34 per cent) and APC (31 per cent),
      and low frequencies (< 20 per cent) near RB1 (16 per cent) and E-cadherin (13 per
      cent). LOH near beta-catenin, HLA, and on 8p occurred at frequencies between 20
      and 30 per cent. The overall frequency of allele loss did not differ among the
      three tumour groups, but some variation was seen at individual loci. There was a
      significantly higher frequency of LOH at 1p35-36 in RER+ tumours compared to RER-
      tumours. Allele loss at this site was also associated with a more advanced Dukes'
      stage at presentation. In addition, RER- tumours showed a higher frequency of
      allele loss at p16 than RER+ tumours. No significant difference existed at any
      locus between the frequency of LOH in sporadic CRC and in UCACRC. Pairwise
      analysis showed a negative association between LOH at APC and DCC, and between
      LOH at chromosome 22p and p53 overexpression. Thus, there may be specific
      differences between the mutation spectra of RER+ and RER- CRCs, but there are
      large degrees of overlap among the underlying genetic pathways of these cancers
      and UCACRCs.

PMID- 9602706
TI  - Expression of oestrogen receptor and oestrogen-inducible genes pS2 and ERD5 in
      large bowel mucosa and cancer.
AB  - Since there is a preponderance of large bowel cancer in males, both in humans and
      in experimental models, and hormone replacement therapy is protective, a role for
      sex steroid hormones in the pathogenesis of this neoplasm seems likely. Evidence
      of functional oestrogen receptor has been looked for in large bowel mucosa and
      cancer. Expression of oestrogen receptor, and of the oestrogen-inducible receptor
      associated genes pS2 and ERD5, was sought. Oestrogen receptor mRNA was detected
      in cancers and paired normal mucosae in equal amounts. In situ hybridization
      identified stromal cells above the muscularis mucosae that were positive for
      oestrogen receptor mRNA. pS2 mRNA was also detected, with a signal intensity
      significantly higher in normal mucosa compared with cancers, whereas the reverse
      was seen with ERD5 mRNA levels. pS2 and ERD5 were expressed in epithelium, with
      the former in a greater amount in distal colon and rectum than proximal colon.
      Although oestrogen-inducible and receptor-associated genes are expressed in large
      bowel mucosa, their expression does not correlate with oestrogen receptor.

PMID- 9602707
TI  - Clinical decision making in Barrett's oesophagus can be supported by computerized
      immunoquantitation and morphometry of features associated with proliferation and
      differentiation.
AB  - Grading of dysplasia in Barrett's oesophagus has a therapeutic impact, but
      subjective grading is associated with substantial observer variation.
      Quantitative pathological methods could help to achieve a more accurate and
      reproducible diagnosis. In the present study, the immunoquantitation of p53 and
      Ki67 and the morphometric analysis of features associated with proliferation and
      differentiation were evaluated for this purpose. In slides of 35 oesophagectomy
      specimens, 73 areas that displayed either no dysplasia (ND), low-grade dysplasia
      (LGD), high-grade dysplasia (HGD), or intramucosal carcinoma (ImCa) were
      initially considered. Agreement on double blind examination by two experienced
      pathologists was reached in 58 areas, which were used as the 'learning set'. The
      15 areas of disagreement were used as a second set. In the univariate analysis,
      the most significant differences in the learning set were found for Ki67, p53,
      stratification index (SI), mean nuclear area, and volume. Further multivariate
      analysis showed that for discrimination between ND and LGD, the combination of
      Ki67 and SI resulted in 94 per cent correctly classified areas. Likewise, for the
      discrimination between LGD and HGD, Ki67 and SI were the most powerful
      combination (again, 94 per cent of areas classified correctly). The
      discrimination between HGD and ImCa with any combination of the quantitative
      parameters never exceeded 80 per cent correct classification. The addition of p53
      was of no value in improving the discrimination of ND vs. LGD, or of LGD vs. HGD.
      In the 15 original disagreement areas of the initial set of 73, three of the five
      ND/LGD areas could be uniquely classified as either ND or LGD by Ki67 and SI.
      Moreover, three of the four LGD/HGD disagreement areas could be uniquely
      classified with the combination of Ki67 and SI as either LGD or HGD. We conclude
      that the quantitative assessment of cytometric and morphometric features
      associated with proliferation and differentiation (especially Ki67 and SI) can be
      a valuable adjunct tool for clinical decision making in Barrett's oesophagus.

PMID- 9602708
TI  - Expression of interferon-gamma receptors and interferon-gamma-induced up
      regulation of intercellular adhesion molecule-1 in basal cell carcinoma;
      decreased expression of IFN-gamma R and shedding of ICAM-1 as a means to escape
      immune surveillance.
AB  - The peritumoural inflammatory infiltrate in basal cell carcinoma (BCC) of the
      skin consists mainly of T lymphocytes which hardly invade the tumour nests. The
      absence of intercellular adhesion molecule-1 (ICAM-1) on BCC cells may explain
      the lack of tumour-infiltrating cells and the lack of an active cell-mediated
      immune response in this tumour. In this study, the induction of ICAM-1 was
      investigated in BCC biopsies using recombinant human interferon-gamma (rHuIFN
      gamma). The expression of interferon-gamma receptors (IFN-gamma R) in the
      biopsies was also investigated. The results showed that BCC cells expressed ICAM
      1 after incubation with rHuIFN-gamma, but to a lesser degree than normal
      epidermal cells. The levels of shed ICAM-1 were significantly increased in the
      culture supernatants of tumour biopsies compared with those from normal skin
      biopsies, after culturing in the presence of rHuIFN-gamma. The expression of IFN
      gamma R was significantly decreased on the tumour cells compared with the
      overlying epidermis. The decreased expression of IFN-gamma R on the tumour cells
      and the shedding of ICAM-1 into the peritumoural stroma may be a plausible
      mechanism by which the tumour cells are protected against an active cell-mediated
      immune response.

PMID- 9602709
TI  - Analysis of the T-cell micro-environment in Epstein-Barr virus-related post
      transplantation B lymphoproliferative disease.
AB  - Epstein-Barr virus (EBV) post-transplantation B lymphoproliferative disease
      (BLPD) may undergo regression after immunosuppression withdrawal and restoration
      of EBV-specific cytotoxic T-cell (CTL) activity in the immunocompromised
      allografted host. The presence of morphologically normal T cells in the BLPD
      micro-environment may influence tumour behaviour in vivo. In this
      immunopathological study, the phenotype and the number of T cells and other
      immunoregulatory cells have been investigated in seven primary and four recurrent
      BLPD biopsies from nine solid organ transplant recipients. BLPD with either viral
      lymphadenopathic or polymorphic lymphoma appearances was found to contain
      sizeable T-cell populations, mainly of memory/helper (TCR alpha/beta +, CD3+,
      CD4+, CD45RO+) type. Cytotoxic (TCR alpha/beta +, CD3, CD8+, Tia-1+) T cells were
      strikingly low in all samples. Low CD28 and CD25 expression suggested that
      secondary signals for functional and sustained T-cell activation may be deficient
      in these tumours. No close correlation was found between the degree of T-cell
      infiltration and clinical outcome, although appreciably higher number of CD8+ T
      cells were detected in three BLPD tumours showing prolonged clinical remission
      after treatment. While some level of EBV-specific T-cell function may be present
      in untreated BLPD, the overall findings of this study suggest that the nature of
      T-cell infiltrates may reflect a response to immunosuppressive therapy rather
      than to EBV infection per se. The possibility that a local EBV-specific T-cell
      response is generated in BLPD undergoing regression after treatment needs to be
      investigated.

PMID- 9602710
TI  - Value of clonality studies of cutaneous T lymphocytes in the diagnosis and follow
      up of patients with mycosis fungoides.
AB  - Histological features of early mycosis fungoides (MF) can simulate numerous
      inflammatory lesions and histological confirmation of MF is often delayed,
      compared with clinical diagnosis. Recently, using molecular techniques, the
      detection of a dominant T-lymphocyte clone has been reported in cutaneous lesions
      of MF. The aim of the present study was to determine the diagnostic value of a
      dominant T-lymphocyte clone as assessed by PCR-DGGE in early MF.
      Histopathological and molecular analyses were performed on cutaneous lesions from
      104 patients clinically suspected as having MF. In this population, the positive
      predictive value of a PCR gamma(+) was 0.86. In addition, four of six patients
      whose lesions were PCR gamma(+) (detectable dominant T-cell clone) but not
      histologically MF progressed to MF within 2-48 months. In order to evaluate the
      relevance of PCR gamma-DGGE in MF follow-up, serial biopsies were performed in 24
      patients. In 89 per cent of cases, the presence or absence of a PCR gamma(+) was
      constant during the course of the disease. When present, the DGGE imprint of PCR
      products was case-specific. These data demonstrate the diagnostic value in MF of
      T-lymphocyte clonality assessed by PCR gamma-DGGE on cutaneous lesions and show
      that the technique can be used in MF follow-up to evaluate residual disease with
      high specificity.

PMID- 9602711
TI  - Neoexpression of the epithelial adhesion complex antigens in thyroid tumours is
      associated with proliferation and squamous differentiation markers.
AB  - Integrin dimer alpha 6 beta 4 is a transmembrane component of an epithelial cell
      adhesion complex that consists of hemidesmosomes (HDs), basement membrane (BM)
      associated laminin-5 (Ln-5), and anchoring filaments/type VII collagen, all of
      which are absent from normal thyroid follicular epithelium. In the present study,
      the expression of epithelial cell adhesion complex antigens in thyroid tumours
      was investigated using immunohistochemistry. In addition to integrin subunits
      alpha 6 and beta 4, immunoreactivity was found for all chains of Ln-5, alpha 3,
      beta 3 and gamma 2, type VII collagen and hemidesmosomal antigen, HD1, in most
      thyroid carcinomas associated with tumour anaplasia and papillary growth pattern
      and located at the border of parenchymal cells and connective tissue or blood
      vessel walls. In addition, a more restricted expression of bullous pemphigoid
      antigens 180 and 230 (BP180 and BP230), constituents of HDs, was found in some
      papillary and anaplastic carcinomas and atypical adenomas. Adhesion complex
      antigens were located to regions of cells which were immunoreactive for
      cytokeratin (ck)-5 and proliferating cell nuclear antigen Ki-67. The results
      suggest that in thyroid carcinomas, the emergence of adhesion complex antigens is
      associated with squamous differentiation and high proliferative activity.

PMID- 9602712
TI  - The development of epithelial phenotypes in the human fetal and infant breast.
AB  - In order to explain the molecular events that contribute to benign and malignant
      breast disease, it is essential to understand the cellular context in which these
      are occurring. This study describes a detailed analysis of the epithelial
      phenotypes in the human fetal and infant breast and provides a starting point for
      such consideration. Using methacarn-fixed, paraffin sections from ten fetal and
      45 infant breast, immunostained with a panel of antibodies to cytoskeletal
      proteins and kappa-casein, it has been possible to define in detail the
      chronological evolution of the major cell types in the human breast from 16 weeks
      of intrauterine life to 2 years of age, in both sexes. Cells at the tips of the
      lobular buds and terminal end buds have a characteristic cytoskeletal protein
      profile, suggesting that they may have the capacity to generate both basal cells
      and luminal cells. Based on the expression of cytoskeletal proteins in the
      developing fetal and infant breast, a model system has been proposed for mammary
      epithelial differentiation.

PMID- 9602713
TI  - Expression of E-cadherin and alpha- and beta-catenins in thymoma.
AB  - Expression of the cell adhesion molecules including E-cadherin and its cytosolic
      binding proteins, alpha- and beta-catenins, has been widely studied in a variety
      of tumours, but not, to date, in thymic epithelial tumours. To observe the
      expression pattern of these adhesion molecules, immunohistochemical stains for E
      cadherin (E-CD) and alpha- and beta-catenins were performed on 89 cases of
      thymoma which were classified as cortical (57 cases), mixed (18 cases), and
      medullary (14 cases), based on the classification of Marino and Muller-Hermelink.
      The majority of cortical thymomas showed diffuse and homogenous membrane
      immunoreactivity for these molecules (88 per cent for E-CD; 86 per cent for alpha
      catenin; 91 per cent for beta-catenin) and the remaining cases showed
      heterogeneous immunoreactivity, whereas almost all mixed and medullary thymomas
      revealed decreased expression or were negative. In each histological subtype of
      thymoma, the expression did not correlate with invasion or with the presence of
      myasthenia gravis. These results indicate that the expression of E-CD and alpha-
      and beta-catenins is more closely associated with the histological subtypes of
      thymoma than with their biological behaviour.

PMID- 9602714
TI  - The retention of abnormal type I procollagen and correlated expression of HSP 47
      in fibroblasts from a patient with lethal osteogenesis imperfecta.
AB  - Various mutations of genes encoding type I procollagen chains have been linked to
      osteogenesis imperfecta (OI). The mutations yield abnormal procollagen molecules
      that fold improperly. HSP 47, a stress-inducible protein localized to the
      endoplasmic reticulum (ER) of collagen-producing cells, may participate in
      collagen processing as a procollagen-specific molecular chaperone. The
      intracellular transport of abnormal procollagen molecules and the expression of
      HSP 47 have been studied in fibroblasts from a patient with OI. Normal and OI
      fibroblasts cultured with or without ascorbate were analysed by immunofluorescent
      double labelling with monoclonal antibodies to C-propeptide of type I procollagen
      and HSP 47, as observed by confocal microscopy. Procollagen and HSP 47 were also
      quantified by immunoprecipitation of normal and OI fibroblasts radiolabelled with
      35S-methionine. By confocal microscopy, procollagen molecules were retained in
      the ER of both fibroblast types cultured in the absence of ascorbate, and were co
      localized with HSP 47. In normal fibroblasts, 2 h after the addition of
      ascorbate, most of the procollagen had disappeared from the cells, while in OI
      fibroblasts, abnormal procollagen molecules and HSP 47 were still retained in the
      ER. By immunoprecipitation, procollagen was negligible in normal fibroblasts
      cultured with ascorbate; much larger amounts of procollagen were
      immunoprecipitated from OI fibroblasts despite ascorbate. Increased HSP 47 in OI
      fibroblasts was demonstrated by immunoprecipitation with a specific monoclonal
      antibody. These results suggest the increase in HSP 47 in the ER of OI
      fibroblasts is related to its collagen-specific chaperone function.

PMID- 9602715
TI  - Association between leukocyte infiltration and development of glomerulosclerosis
      in experimental lupus nephritis.
AB  - Mice with chronic graft-versus-host disease (GvHD) induced by injection of DBA/2
      lymphocytes into (DBA/2 x C57BL/10) F1 hybrids (DBA/2 GvHD) develop a lupus-like
      glomerulonephritis with global glomerulosclerosis 12 weeks after induction of the
      disease. In two other strain combinations with similar H-2 incompatibilities
      [BALB/c into BALB/c x BL10 (BALB/c GvHD) and BALB.D2 into BALB.D2 x BL10 (BALB.D2
      GvHD)], GvHD induction leads to lupus nephritis without global
      glomerulosclerosis. This study investigated the identity of kidney-infiltrating
      leukocytes and their involvement in the development of glomerulosclerosis in
      these three strain combinations. In mice with DBA/2 GvHD, a significant increase
      in glomerular CD11a-positive cells was found 4 weeks after disease induction.
      Mice with BALB/c or BALB.D2 GvHD did not show an increase in glomerular CD11a
      positive cells at any time point. In the interstitium, CD11a-positive cells were
      observed 4 weeks after disease induction only in mice with DBA/2 GvHD. In mice
      with BALB.D2 GvHD, no increase was found in interstitial CD11a-positive cells. In
      mice with BALB/c GvHD, interstitial CD11a-positive cells were found from week 4
      onward. Further immunohistochemical analysis of the glomerular CD11a-positive
      cells in mice with DBA/2 GvHD showed that these cells were neither
      polymorphonuclear leukocytes (PMN), nor CD3-positive (T cells), B220-positive (B
      cells), or F4/80-positive (macrophages). They were all CD45-positive (leukocytes)
      and MHC class II-positive. In conclusion, we have shown in this model of chronic
      lupus nephritis that glomerular influx of as yet unidentified CD11a-positive
      leukocytes is associated with the development of glomerulosclerosis.

PMID- 9602716
TI  - Role of neuropeptides and amino acids in controlling secretion of hormones from
      the anterior pituitary gland in pigs.
AB  - All reproductive processes involve one or more of the protein hormones secreted
      from the anterior pituitary gland: LH, FSH, prolactin, growth hormone, ACTH and
      thyroid-stimulating hormone (TSH). Primary hormones of reproduction, such as LH
      and FSH, directly regulate a reproductive activity. For example, LH and FSH
      stimulate follicular growth and the associated secretion of oestradiol in sows.
      In contrast, secondary hormones of reproduction such as TSH are permissive and
      regulate other physiological systems that indirectly, but profoundly, influence
      reproduction. Reproduction in pigs can be enhanced by developing strategies to
      alter and control secretion of hormones from the anterior pituitary gland.
      However, the successful manipulation of adenohypophysial hormone secretion will
      require a sound understanding of the mechanisms controlling the function of the
      hypothalamic-pituitary axis. Hypothalamic hormones including GnRH, dopamine,
      growth hormone-releasing hormone (GHRH), somatostatin, corticotrophin-releasing
      hormone (CRH) and thyrotrophin-releasing hormone (TRH) are synthesized in
      perikarya that possess axons that terminate at the median eminence. These
      hormones are released into the hypothalamo-hypophysial portal vasculature, travel
      to the anterior pituitary gland and stimulate or inhibit secretion of
      adenohypophysial hormones. Secretion of hypothalamic hormones is ultimately
      controlled by a variety of neurotransmitters and neuropeptides, the most studied
      in swine being the endogenous opioid peptides (EOP) and more recently, the
      excitatory amino acids (ExAA). In general, EOP inhibit GnRH and hence LH
      secretion, and this effect involves the central catecholaminergic system. A
      definitive role for EOP in the modulation of FSH release remains to be
      determined. EOP stimulate secretion of GHRH and thus growth hormone release, and
      depending on the animal model studied, EOP exert either stimulatory or inhibitory
      influences on prolactin secretion. ExAA, working via N-methyl-D-aspartate (NMDA)
      receptors at the central nervous system, stimulate secretion of LH, FSH, growth
      hormone and prolactin in appropriate animal models. However, in certain
      situations, an inhibitory effect of ExAA on LH secretion has been demonstrated.
      The modulation of growth hormone and prolactin secretion by ExAA involves EOP.
      Research investigating the function of ExAA and EOP in the physiological control
      of swine reproduction warrants further scrutiny.

PMID- 9602717
TI  - Immune-endocrine interactions affecting luteal function in pigs.
AB  - The formation, normal function and destruction of corpora lutea are essential
      features of normal reproduction. Although the formation of corpora lutea from
      follicles is largely dependent on pituitary gonadotrophins, the process of
      luteolysis is locally regulated and poorly understood. The corpus luteum consists
      of several steroidogenic and nonsteroidogenic cell types that interact with each
      other in a paracrine manner. Under cell culture conditions, large luteal cells
      that stem from follicular granulosa cells can be identified easily under the
      microscope and collected individually for single cell RT-PCR. As each of the 120
      large luteal cells express the gene encoding 3 beta-hydroxysteroid dehydrogenase,
      it appears that all large luteal cells are steroidogenic. Large luteal cells also
      express the oestrogen receptor gene and as they are known to produce oestradiol,
      it can be concluded that the steroid acts in an auto- or intracrine manner in
      large luteal cells. Since we showed previously that oestradiol stimulates
      progesterone release under in vitro and in vivo conditions, it can be concluded
      that the steroid is an important intraluteally acting luteotrophic signal. At the
      time of luteal regression, macrophages invade the corpora lutea and their
      cytokine products, particularly tumour necrosis factor alpha (TNF alpha), appear
      to be involved in reduced steroid secretion. Indeed, TNF alpha inhibits
      production of progesterone and oestradiol from cultivated luteal cells. In sows,
      oestradiol is a strong luteotrophic factor and the production of oestradiol and
      of its receptor is downregulated by TNF alpha. Thereby, TNF alpha not only exerts
      direct luteolytic effects but also prevents the luteotrophic effects of
      oestradiol. Hence, it has an anti-luteotrophic action. In most species,
      functional luteolysis is accompanied by morphological regression of the corpus
      luteum. This structural luteolysis also appears to involve TNF alpha, as we have
      shown in pigs that expression of TNF alpha gene is high during luteolysis.
      Furthermore, TNF alpha stimulates programmed cell death (apoptosis) in luteal
      cells kept under culture conditions.

PMID- 9602718
TI  - Control of follicular development and ovulation rate in pigs.
AB  - There is considerable evidence that nutritional and metabolic control of
      follicular growth is mediated by metabolic hormones and growth factors,
      particularly with processes mediated by insulin-like growth factor I (IGF-I) and
      its binding proteins (IGFBPs). From knowledge that hormones and growth factors
      which can be affected by diet also positively affect ovarian function, the
      concept has emerged that metabolic modifiers of gonadotrophin action, rather than
      gonadotrophins themselves, could affect follicle development. While ovulation
      rate can be enhanced under certain conditions in cyclic gilts, assessing
      influences of metabolic modifiers on the post-lactational sow is confounded by
      variability in the return to oestrus after weaning. In a series of studies
      involving insulin administration between weaning and oestrus, successive
      experiments produced different results, but several measures of reproductive
      performance were enhanced. Administration of somatotrophin (ST) has also been
      shown to increase follicular development in both gilts and sows. Both insulin and
      ST increase IGF-I production by pig ovarian follicles, and insulin is more
      effective than IGF-I in reducing atresia and increasing progesterone in cultured
      pig follicles. Whether increases in litter size are achieved after an increase in
      ovulation rate involves many factors, including the quality of ova and whether
      the increase in ovulation rate exceeds the uterine capacity to maintain
      pregnancy. Given the variation in genetics and management practices, development
      of treatments to enhance follicle quality leading to maximal litter size is
      challenging.

PMID- 9602719
TI  - Mechanisms mediating nutritional effects on embryonic survival in pigs.
AB  - The inconsistency of data from experiments designed to show nutritional effects
      on embryonic survival is perplexing. However, a number of experimental models
      have provided some insight into the mechanisms that potentially mediate
      interactions between nutrition, metabolic state and embryonic survival. The
      developing ovarian follicle provides the maturational environment for the oocyte,
      and differences in follicular maturation are associated with differences in the
      ability of these follicles to support oocyte maturation. In turn, the rate of
      oocyte maturation and the maturational state of the oocyte immediately before
      ovulation may contribute to differences in embryonic survival. Therefore,
      evidence that nutritionally induced differences in metabolic state affect
      follicular development and the maturational state of the oocyte in the late
      follicular phase may constitute a mechanism by which nutrition affects the very
      early stages of conceptus development. Once ovulation occurs, the process of
      fertilization and early cleavage occurs in the environment of the oviduct.
      Nutritional state might affect the secretory and motile activity of the oviduct
      both directly, by influencing the physiology of the oviductal cells, or
      indirectly by affecting the secretion of key regulatory hormones. Thus evidence
      for nutritionally dependent effects on plasma progesterone concentrations in
      early pregnancy and associations with differences in embryonic survival may be
      partly mediated at the oviductal stage of development. Nutritional effects on
      circulating progesterone concentrations may also affect the uterine environment.
      However, the metabolic state of the gilt or sow, or specific nutrients in the
      diet, may directly affect the integrity of the endometrium and thus affect
      embryonic survival at this stage of development.

PMID- 9602720
TI  - Management of boars for efficient semen production.
AB  - Consistent production of large quantities of fertile semen is a primary concern
      of boar management programmes. Common visual tests such as motility are poor
      indicators of the fertilizing capacity of an ejaculate. Research studies have
      demonstrated that, in general, if motility is 60% or greater, there are no
      relationships among the percentage of motile spermatozoa, in vitro sperm
      penetration rates, farrowing rates and litter size. Biological and environmental
      factors that influence the production of total numbers of spermatozoa are either
      inhibitory or stimulatory. Chronic undernutrition and heat stress inhibit
      spermatogenesis, while photoperiod and genetic factors are stimulatory. A
      consistent stimulatory effect of photoperiod does not appear to occur under all
      environmental conditions. In contrast, selection for increased testis size
      consistently results in greater sperm production. In addition, libido is
      decreased by heat stress and undernutrition. However, failure to allow boars to
      interact socially with other pigs during pubertal development appears to be the
      most damaging factor. Effective boar management programmes must minimize the
      occurrence of factors that adversely affect spermatogenesis and simultaneously
      accentuate those with a stimulatory role.

PMID- 9602721
TI  - Consequences of variation in interval from insemination to ovulation on
      fertilization in pigs.
AB  - This review describes effects of variation in the interval between insemination
      and ovulation on the fertilization process in the sow. Inseminations performed
      too early or too late relative to ovulation decrease litter size and especially
      farrowing rate. This effect can be explained to a large extent by the increase in
      the percentage of non-fertilized eggs, resulting in partial fertilization or no
      fertilization at all. No effects of variation in the interval from insemination
      to ovulation are found on the percentage of degenerate embryos. Only moderate
      effects are found on mean embryonic development and variation in embryonic
      development at day 5 after insemination. In general, insemination between 0 and
      24 h before ovulation gives good fertilization results. Factors influencing the
      optimal interval from insemination to ovulation, such as number of sperm cells
      used for insemination, storage time of liquid semen and use of frozen semen, and
      sow factors such as parity and breed are discussed.

PMID- 9602722
TI  - Expression of oestrus and timing of ovulation in pigs.
AB  - Oestrus is the period around ovulation in which sows show a standing response for
      boars, thus allowing the boars to mate with the sows. The duration of oestrus may
      vary between sows from 24 h up to 96 h, which is not related to systemic
      oestrogen concentrations. The moment of ovulation after onset of oestrus may vary
      from 10 h to 85 h. Consequently, onset of oestrus is not a good predictor for the
      time of ovulation. A reliable prediction of ovulation time would be worthwhile,
      since fertilization results are highly dependent on the moment of insemination
      relative to the moment of ovulation. However, at present, the duration of oestrus
      is the best 'predictor' of ovulation time and is independent of the duration of
      oestrus; ovulation takes place on average 70% of the way through oestrus. The
      following factors have been found to influence the duration of oestrus (and
      consequently the optimal time for insemination): boar-stimuli, stress, interval
      from weaning to oestrus, season and parity. Further study is needed to determine
      the causes of the variability in oestrus expression between sows, including the
      regulation of oestrus behaviour at the level of the brain.

PMID- 9602723
TI  - Effects of semen components on ovulation and fertilization.
AB  - In pigs, transcervical infusion of seminal plasma at the onset of oestrus
      advances ovulation and thus improves the chance of gametes meeting during their
      full fertilizing competence. An animal model that allows single uterine horn
      infusion was used in combination with transcutaneous sonographic monitoring of
      ovaries. Preparative surgery involved the detachment of one uterine horn from the
      corpus, leaving the caudal end open to the peritoneal cavity but sealing the
      corpus wound. Transcervical infusion of 100 ml seminal plasma immediately after
      the detection of oestrus advanced ovulation by between 8 and 14 h on the
      ipsilateral ovary adjacent to the infused horn compared with the contralateral
      ovary. In addition, the seminal plasma infusion did not influence the LH profile
      compared with uterine infusion of PBS. This finding indicates that the effect is
      mediated by a local mechanism in the female genital tract. The advancement of
      ovulation depends on the time of infusion early in oestrus and is more pronounced
      in gilts exhibiting a long interval between the onset of oestrus and spontaneous
      ovulation compared with early ovulators. At 24 h after the detection of oestrus,
      seminal plasma was ineffective. Apparently, seminal plasma does not affect
      maturation and fertilizing competence of oocytes. The activity resides in a low
      molecular mass protein fraction and, to a far lesser extent, in seminal
      oestrogens. Further characterization of the active components may allow a
      practical application in AI.

PMID- 9602724
TI  - Role of uterine immune cells in early pregnancy in pigs.
AB  - The immune system discriminates 'self' from 'non-self', and eliminates that which
      it determines to be non-self. Mammalian pregnancy appears to represent a failure
      of self-non-self discrimination, yet it is a highly successful reproductive
      strategy. We present evidence that the immune system of the female pig responds
      to the challenges of both mating and the presence of conceptuses. Mating induces
      an influx of inflammatory leukocytes into the endometrial stroma and uterine
      lumen. This response, while partially under endocrine control, is amplified by as
      yet unidentified factors in seminal plasma. In addition to preventing microbial
      infection, this mating-induced immune response may enhance reproductive
      performance. During the first month of pregnancy when intimate contact between
      maternal and fetal tissues is being established, the number of uterine
      lymphocytes decrease in the luminal epithelium and increase in the endometrial
      stroma at sites of conceptus attachment. The majority of these lymphocytes
      express the CD2 and CD8 surface markers, consistent with either T or natural
      killer (NK) cell lineage. Dispersed endometrial cells obtained during early
      gestation exhibit a pregnancy-specific increase in NK-like lytic activity. Our
      ongoing efforts to determine whether these NK-like lymphocytes are the ones that
      localize to sites of conceptus attachment are discussed. We speculate on how the
      reactions of pig uterine leukocytes to seminal plasma and conceptuses might
      contribute to successful pregnancy.

PMID- 9602725
TI  - Regulation of conceptus development and attachment in pigs.
AB  - Implantation/placentation in domestic pigs is preceded by synthesis of oestrogen
      by the conceptus to maintain functional corpora lutea throughout pregnancy and a
      rapid morphological transformation of conceptuses from spherical to long
      filamentous thread-like structures. Initial conceptus expansion, reaching a metre
      in length, not only delineates the surface area for placental attachment, but
      also provides the mechanism for delivery of oestrogen to signal events necessary
      for placentation throughout the uterine horn. Timing for conceptus gene
      expression to induce trophoblast expansion and attachment in pigs is temporally
      associated with downregulation of progesterone receptors and increase in
      oestrogen receptors within the uterine epithelium. Within the confines of the
      uterine lumen, pig conceptuses normally do not erode or invade through the
      uterine epithelial surface. However, the pig conceptus possesses extensive
      proteolytic activity as it is highly invasive outside the uterine lumen of the
      pig. Initial release of oestrogen by the elongating pig conceptus induces
      endometrial release of cytokines and a variety of protease inhibitors. Recently,
      endometrial expression for the inter-trypsin inhibitor (I alpha I) family of
      protease inhibitors has been detected in the pig endometrium during conceptus
      elongation and attachment. It is possible that I alpha Is may function to inhibit
      trophoblast invasion and also serve as targets for adhesion molecules, such as
      integrins and heparin, to aid in placental attachment to the uterine epithelium.

PMID- 9602727
TI  - Embryonic and fetal development in different genotypes in pigs.
AB  - It is widely accepted that uterine capacity, not ovulation rate, is the greatest
      restraint on litter size in pigs. Recently, the reproductive strategy(s) of the
      Chinese Meishan pig, a breed which farrows three to five more piglets per litter
      than US or European pig breeds, has come under intense scrutiny. It was initially
      determined that the Meishan female could farrow more viable piglets per litter
      than US or European pig breeds, with a uterine size and ovulation rate equivalent
      to those of less prolific breeds. It has become apparent that the Meishan
      conceptus exhibits a reduced trophectoderm mitotic rate during the
      preimplantation period, elongates from fewer cells and remains smaller throughout
      gestation compared with conceptuses from less prolific US or European pig breeds.
      This strategy by the Meishan conceptus for a lower growth rate results in a
      marked reduction in conceptus loss through day 18 of gestation compared with less
      prolific breeds. An additional strategy is required in the Meishan to allow the
      larger number of viable fetuses to survive after day 30 of gestation when uterine
      capacity becomes limiting. Our research has demonstrated that the rapid growth of
      the fetus in US pig breeds appears to require continued placental growth to
      increase the surface area for nutrient exchange. In contrast, the increased
      number of smaller Meishan fetuses achieve the same increase in placental
      efficiency by markedly increasing the density of placental blood vessels at the
      fetal-maternal interface. This proliferation of placental blood vessels obviates
      the need for marked increase in placental size.

PMID- 9602726
TI  - Extracellular matrix and the implantation cascade in pigs.
AB  - The structural and functional alterations of uterine epithelial cells that permit
      the apical-apical union of conceptus and uterine epithelium are complex and are
      likely to involve many different adhesion molecules with distinct but inter
      related functions. A number of changes in the molecular composition at the apical
      surface of uterine epithelial cells associated with the transition from the pre
      receptive to the receptive state in the pig uterus are reviewed. Molecules that
      function in the adhesion cascade resulting in implantation are represented by a
      variety of adhesion systems. However, integrins are probably the dominant
      adhesion systems because their capacity to mediate adhesion is linked to their
      activation by engaging other surface molecules.

PMID- 9602728
TI  - Physiology of the Meishan boar.
AB  - Onset of puberty (sperm production) occurs at a much younger age (56-84 days) in
      Meishans than in conventional boars (120-180 days). Throughout postnatal
      development, Meishans exhibit markedly higher (two- to ten-fold) concentrations
      of serum FSH, LH and androgens compared with conventional boars, and these high
      hormone concentrations are maintained at maturity. Increased gonadotrophin
      concentrations occur only in Meishan males, since concentrations in female
      Meishans and conventional females do not differ. In the Meishan boar, FSH
      increases steadily during establishment of sperm production and LH increases
      markedly after tubule diameter stabilizes, while FSH and LH concentrations are
      low and change little during this period of rapid testicular growth in
      conventional boars. The proportion of the testis occupied by Leydig cells is two
      fold greater and average Leydig cell size is two- to four-fold larger in Meishans
      than in conventional boars during the onset of spermatogenesis and into maturity.
      Testis size in Meishans is only half that of conventional boars at maturity, and
      the number of Sertoli cells is markedly reduced in Meishans. However, Meishan
      testes exhibit reduced degeneration of germ cells and spermatids during
      spermatogenesis, and spermatogenic efficiency per Sertoli cell in Meishans is
      double that in conventional boars. At maturity, Meishan pituitaries have greater
      mass, larger gonadotrophs, higher content of FSH, and greater expression of genes
      for FSH and LH subunits than found in conventional boars. The high concentrations
      of serum gonadotrophins in the mature Meishan exhibit a typical postcastration
      rise, respond to GnRH stimulation and are suppressed by gonadal steroids,
      indicating that the hypothalamo-pituitary-gonadal axis functions normally but
      with much higher set points in Meishan boars. These unusual endocrine and
      physiological attributes in boars of the highly prolific Meishan breed offer a
      unique model for further investigation of factors influencing early onset of
      puberty and efficiency of male reproductive function.

PMID- 9602729
TI  - Sperm plasma membrane characteristics and boar semen fertility.
AB  - Much effort is being made to establish relationships between the molecular events
      that take place in spermatozoa under fertilizing conditions and actual sperm
      function during fertilization. During capacitation, the process that 'primes'
      spermatozoa for interaction with the egg, components of the sperm's environment,
      notably bicarbonate, provoke various specific changes in the architecture and
      functioning of the sperm plasma membrane in a large number of cells. The
      individual changes have been found to proceed on different time scales, and may
      therefore represent sequential stages in the capacitation process. However, each
      change takes place at different rates in individual cells, revealing considerable
      functional heterogeneity within the sperm population. Recent work on membrane
      changes provoked by cooling has indicated similarities with capacitational
      changes. The effect of cooling may therefore be to induce premature capacitation
      (and destabilization). Such an effect would greatly compromise sperm fertilizing
      potential. A pig sperm-egg interaction model was used to examine quantitative
      details of zona binding and zona penetrating abilities within capacitated sperm
      populations, and sperm behaviour was found not to accord with generally held
      beliefs. In particular, individual spermatozoa that have bound to the zona
      pellucida show great variation in the delay before penetrating: no evidence has
      been found for a specially competent subgroup. Even in sperm samples incubated to
      undergo maximal capacitational membrane changes, cells with actual penetrating
      potential represent less than 15% of the total number that attach initially to
      the zona pellucida. Thus detection of capacitational membrane changes appears
      greatly to overestimate zona penetrating capability. Future studies linking sperm
      membrane characteristics with semen fertility in the field will need to consider
      differences between in vitro and in vivo conditions. The need for survival in the
      female tract may require much slower sperm responses than are considered optimal
      for in vitro fertilization.

PMID- 9602730
TI  - Assessment of boar sperm function in relation to freezing and storage.
AB  - The functions necessary for normal fertilization to occur in vivo or in vitro are
      examined and a rational approach to identifying the main features of a
      fertilizing spermatozoon are developed. It is concluded that methods for testing
      the quality of spermatozoa must probe the dynamic changes experienced by the
      spermatozoa during capacitation or under stressful incubation conditions. Recent
      developments in the multivariate analysis of sperm motility data are used to
      illustrate the success that can be achieved by this approach. Ideally, changes in
      sperm motility characteristics should be correlated with an assessment of
      capacitation status. However, until the capacitation status of any individual
      cell can be clearly defined this will remain problematic.

PMID- 9602731
TI  - Molecular approaches to improved pig fertility.
AB  - Geneticists have made limited progress in improving reproductive traits in pigs
      through traditional selection and crossbreeding systems. Recent advances in
      molecular genetics and the human genome project have allowed progress in gene
      identification and gene mapping in pigs. The pig genetic linkage map now has over
      1700 genetic markers, and about 200 of these are genes. Furthermore, comparative
      genomic maps are improving and are becoming useful tools. Molecular approaches
      such as candidate gene identification and genomic scans permit new genes and
      chromosomal regions to be discovered which may influence reproduction. One
      significant finding is that the oestrogen receptor locus (ESR) is associated with
      increased litter size. Differences between female Chinese pig ESR BB and AA
      homozygotes have averaged 2.3 pigs born alive for first parity, and in commercial
      Large White crosses the differences are about 0.9 pigs per litter. Additional new
      genes have been discovered which may significantly affect litter size. Initial
      genome scans have revealed that there may be a gene or genes influencing
      ovulation rate and litter size on chromosome 8. Approaches such as positional
      comparative candidate gene analysis and eventually positional cloning will
      probably identify the genes controlling reproduction in pigs.

PMID- 9602732
TI  - Developments in transgenic techniques in pigs.
AB  - Manipulation of the pig genome is currently restricted to the random insertion of
      new DNA using pronuclear microinjection. This method suffers from a number of
      inherent limitations, the majority of which result from the inability to control
      the site at which the transgene becomes integrated. These drawbacks, together
      with the need to be able to target existing genes, will result in the replacement
      of pronuclear injection by new methods that have the capability to direct
      insertion to a particular genomic site that does not influence expression.
      Currently, it is possible to control the site of insertion in mice using
      embryonic stem (ES) cell and homologous recombination technologies. However,
      pluripotent ES cells have yet to be isolated in pigs. The possibility of using
      nuclear transfer to reprogramme early differentiated embryonic cells as well as
      somatic cells from adult animals may provide an alternative method for generating
      precise genetic modifications. Methods that allow these changes to be carried out
      in situ are also likely to be developed in the future.

PMID- 9602733
TI  - Advances in the generation of transgenic pigs via embryo-derived and primordial
      germ cell-derived cells.
AB  - The development of new technologies that would increase the efficiency for
      generation of transgenic livestock and would overcome some of the problems
      associated with random insertion of the transgene will greatly benefit animal
      agriculture. A potential alternative technology to pronuclear injection for the
      generation of transgenic pigs involves the isolation, culture and genetic
      manipulation of cell lines that can be reintroduced into the embryo for
      participation in the formation of the germ cells. We have isolated and cultured
      pig primordial germ cells (PGC) while maintaining them in an undifferentiated
      state as determined by morphology and alkaline phosphatase (AP) activity. More
      importantly, PGC-derived cells were stably transformed with the green fluorescent
      protein marker driven by the cytomegalovirus promoter. After visual
      identification of transgenic colonies, the pluripotential characteristics of the
      transgenic PGC-derived cells were tested by chimaera formation and to date we
      have identified, by genomic Southern blots, two chimaeric fetuses that contain
      tissues with the transgene incorporated into their chromosomes. To our knowledge,
      this is the first report of a chimaeric transgenic pig fetus obtained via a
      cultured cell line.

PMID- 9602734
TI  - Advances in gender preselection in swine.
AB  - Gender preselection using isolated populations of X- and Y-chromosome bearing
      spermatozoa that have been separated on the basis of DNA content is currently
      possible in swine and other farm animals, as well as in humans. Semen from most
      livestock species can now be successfully separated into predominantly X or Y
      sperm populations before their use for intra-tubal insemination, deep-uterine
      insemination or for in vitro fertilization (IVF) to produce sexed offspring.
      Birth of progeny of the desired sex in cattle, sheep and swine under semi
      practical conditions has successfully validated the sexing technology.
      Spermatozoa are separated on the basis of inherent differences in DNA content in
      the X- and Y-chromosome bearing sperm population using modified flow
      cytometry/cell sorting technology. Spermatozoa are stained with Hoechst 33342
      which binds to the DNA in an amount proportional to the amount of DNA present in
      the individual spermatozoa. Over 300 animals from various species at several
      locations have been born using the USDA-Beltsville Sperm Sexing Technology for
      separating X and Y spermatozoa. Sex ratios are shifted from the normal 50:50 to
      85 to 90% of one sex or the other. In swine, offspring have been born as the
      result of surgical intratubal insemination of separated spermatozoa and also from
      IVF and embryo transfer. At the present time, standard swine artificial
      insemination techniques are not optimized for use with the small numbers of flow
      cytometrically separated X or Y sperm populations. Cattle, swine and rabbit
      offspring have been reproduced through the second generation with normal
      morphology and reproductive function. Numerous improvements have been made in the
      sexing technology since it was first reported in 1989. Increasing the speed of
      the sexing process to make the application of the technology available to a
      larger segment of the livestock industry is paramount, even with insemination
      technology designed for small numbers of spermatozoa.

PMID- 9602735
TI  - Advances in in vitro production of pig embryos.
AB  - A series of integrated, effective techniques is required to produce pig embryos
      from follicular oocytes in vitro. The failure to form a male pronucleus and
      polyspermy have been serious problems in efforts to produce embryos efficiently
      in vitro from pig oocytes. The former problem is now considered to be due to
      oxidative stress and the latter has been partially solved by reducing the number
      of capacitated spermatozoa reaching the oocytes. By the use of new technology for
      in vitro production of embryos, an acceptable rate of blastocyst formation and
      the birth of live piglets has been achieved. However, even with the use of these
      improved in vitro maturation (IVM) and fertilization (IVF) conditions, the
      efficiency of production of in vitro blastocysts and offspring still remains
      relatively low. More recently the developmental competence of embryos matured and
      fertilized in vitro has been investigated through modification of culture
      conditions of oocytes during the germinal vesicle stage. Oocyte competence for
      early embryonic development appears to be achieved by active communication
      between the oocyte and follicular cells. Since the ovarian oocytes available for
      IVM are primarily those present in mid-size antral follicles of prepubertal
      gilts, more research is needed to gain an improved understanding of the culture
      conditions required to induce developmental competence in oocytes from both
      preantral and antral follicles as well as additional modifications in IVF systems
      to overcome the problem of polyspermic penetration.

PMID- 9602736
TI  - Oviductal regulation of fertilization and early embryonic development.
AB  - During the period of late follicular development and the first four days of the
      oestrous cycle, the oviduct occupies a central role in the establishment of
      pregnancy. Oviductal function is regarded as being either 'passive' or
      biologically active, providing an environment that sustains and enhances
      fertilization and early cleavage-stage embryonic development. Recent reports have
      focused on this microenvironment and shown that ovarian steroids induce marked
      morphological, physiological and biochemical changes. Alterations include changes
      in the biosynthetic activity and release of macromolecules by the oviductal
      epithelium which become part of the luminal microenvironment. Furthermore, both
      regional and temporal differences in activity and protein production occur
      through hormonal changes during the oestrous cycle and early pregnancy. Studies
      on identification, characterization and regulation of several proteins
      synthesized de novo have indicated oocyte-oviduct and embryo-oviduct
      interactions. However, the identification of oviduct-derived proteins, their
      regulation and their potential function in vivo needs to be examined. Studies in
      other species also suggest roles for growth factors in early embryonic
      development, but little information is available for the pig. We propose that
      ovarian hormones control changes in synthetic activity, synthesis of some oviduct
      derived proteins and the presence of specific factors in the luminal
      microenvironment which sustain and enhance fertilization and early cleavage-stage
      embryonic development.

PMID- 9602737
TI  - Cryopreservation of pig embryos.
AB  - The changing global needs for food and animal products require the development of
      breeding strategies for maximizing genetic improvement while maintaining genetic
      diversity. Genetic diversity can be conserved by using separate breeding herds;
      however, they may be expensive to maintain and inbreeding becomes a major
      concern. Alternative methods are needed to preserve valuable genetic resources in
      a reasonable and economic manner. Embryo cryopreservation allows indefinite
      storage in vitro at subambient temperatures where metabolism and other cellular
      functions are greatly reduced or cease, and upon recovery from storage, normal
      developmental competence can be resumed. Storage and transportation require
      little maintenance and there is no expense in animal care and little concern
      about disease transmission. Although there are methods for routine
      cryopreservation of germplasm and embryos of most livestock species, development
      of this technology in the pig industry is far behind and has abated improvements
      in genetic potential. Pig embryos are very sensitive to hypothermic conditions,
      and this limits their ability to withstand many conventional methods of
      preservation. Much research has focused on the high lipid content of pig embryos,
      and its role in hypothermic sensitivity and cryosurvival. Many studies have
      reported the conventional freezing of pig embryos, and vitrification has shown
      promise of eluding the difficulties associated with cooling sensitivity and ice
      crystallization. Recent research suggests that the embryonic cytoskeleton is
      susceptible to damage during cryopreservation, and this cellular disruption may
      be averted by using cytoskeletal stabilizers before preservation. Embryos
      cryopreserved by conventional freezing and vitrification under the influence of
      cytoskeletal stabilization have resulted in pregnancies or live offspring from
      recipient females after surgical transfer. Although cryopreservation technology
      is less advanced in pigs than in other livestock species, promising research
      shows evidence that researchers are close to achieving a methodology for
      preserving pig embryos.

PMID- 9602738
TI  - The duty of continuity.

PMID- 9602739
TI  - A confusion of roles: manpower in the National Health Service.

PMID- 9602740
TI  - Common mental disorders, explanatory models and consultation behaviour among
      Indian women living in the UK.
AB  - Women of Indian origin are said to have a lower rate of recognized common mental
      disorders and a higher frequency of consultation in primary care than white
      British. The aim of this study was to evaluate factors, including explanatory
      models (patient perspectives) of illness, associated with common mental disorders
      and with frequency of consultation among women of Indian origin in primary care.
      The investigation was conducted in a general practice in West London with a large
      Indian population. Consecutive woman attenders of Indian descent were screened
      with the General Health Questionnaire-12 to identify probable cases of
      psychiatric morbidity. 100 patients were interviewed with the Revised Clinical
      Interview Schedule (CIS-R), a specific tool for the diagnosis of common mental
      disorders, and the Short Explanatory Model Interview, which elicits the
      individual's conceptualization of his or her illness. Those patients who
      satisfied CIS-R criteria were classified as 'cases', the others as 'controls'.
      Common mental disorders were documented in 30% of patients. The general
      practitioner's diagnosis of common mental disorders had a sensitivity of 17% and
      a specificity of 91%. Individuals with common mental disorders had a higher
      frequency of consultation (P = 0.017), were less likely to see depression as an
      indication for medical intervention and were more likely to withhold some of
      their concerns from the general practitioner. Incorrect diagnosis by the GP was
      most likely to occur when patients did not disclose all their complaints. These
      associations were all statistically significant after adjustment for possible
      confounders by multiple linear and logistic regression. Women of Indian origin in
      this sample had rates of common mental disorders similar to those in other UK
      populations. Differing conceptualizations of common mental disorders may
      contribute to their underrecognition in women of Indian origin.

PMID- 9602741
TI  - An audit of the investigation and treatment of folic acid deficiency.
AB  - On the suspicion that folate deficiency was not being thoroughly investigated we
      conducted a retrospective study of management in a teaching hospital. Notes from
      84 consecutive patients with low red cell folates (mean age 69.5 years, range 21
      95, M:F 33:51) were reviewed for haemoglobin, mean cell volume, dietary history,
      alcohol consumption, drug history, relevant medical history, relevant
      investigations, treatment, repeat measurement of red cell folate and diagnosis of
      deficiency. In 52 (61.9%, mean age 72.9 years, range 33-95, M:F 21:51) no
      diagnosis was reached. In only 32 (38.1%, mean age 63.9 years, range 21-89, M:F
      12:20) was a definitive diagnosis established: 5 had coeliac disease, 1 had
      Crohn's disease, 9 had drug-associated deficiency (4 methotrexate, 3 phenytoin, 1
      trimethoprim and 1 valproate), 1 had combined variable immunodeficiency and 16
      had dietary deficiency. In most cases of folic acid deficiency no attempt was
      made to establish aetiology. We recommend that younger patients without an
      obvious cause are investigated initially by dietary assessment and measurement of
      anti-endomysial antibody and by duodenal biopsy with small-bowel follow-through
      if clinically indicated.

PMID- 9602742
TI  - Evidence-based medicine on the Internet.

PMID- 9602743
TI  - The demise of the D&C.

PMID- 9602744
TI  - Does constipation cause abdominal pain in childhood?

PMID- 9602745
TI  - Scombroid poisoning--a pseudoallergic syndrome.

PMID- 9602746
TI  - Hereditary sensory and autonomic neuropathy with anhidrosis (type IV).

PMID- 9602747
TI  - Salivary pleomorphic adenoma in familial adenomatous polyposis.

PMID- 9602748
TI  - Acute sciatica with an infective cause.

PMID- 9602749
TI  - Back pain during pregnancy and after childbirth: an unusual cause not to miss.

PMID- 9602750
TI  - Celestin blister with obstruction.

PMID- 9602751
TI  - Presentation of colonic carcinoma via genetic testing in the offspring.

PMID- 9602752
TI  - Zollinger-Ellison syndrome with fasting hypoglycaemia.

PMID- 9602753
TI  - Colo-colonic intussusception due to lipoma.

PMID- 9602754
TI  - Lord Moran's memoir: shell-shock and the pathology of fear.

PMID- 9602755
TI  - Paul-Louis Simond and his discovery of plague transmission by rat fleas: a
      centenary.

PMID- 9602756
TI  - Vicq d'Azyr and a cattle plague.

PMID- 9602757
TI  - God's bad air day.

PMID- 9602758
TI  - Monteggia fracture treated by external fixation.

PMID- 9602759
TI  - Transient ptosis and miosis after rugby injury.

PMID- 9602760
TI  - Origin of the myth of vampirism.

PMID- 9602761
TI  - Radiotherapy for perianal Paget's disease.

PMID- 9602762
TI  - Heterotopic ossification.

PMID- 9602763
TI  - Indomethacin for prevention of heterotopic ossification after hip arthroplasty. A
      randomized comparison between 4 and 8 days of treatment.
AB  - In a randomized, parallel group study, we evaluated the efficacy of a 4-day
      versus an 8-day course of indomethacin (50 mg, 3 times per day), given as
      prophylaxis against heterotopic ossification after cementless total hip
      arthroplasty in 209 patients with arthrosis. Patients receiving the prophylaxis
      for 8 days had less (p = 0.03) severe heterotopic bone formation.

PMID- 9602764
TI  - Preventive effects of ibuprofen on periarticular heterotopic ossification after
      total hip arthroplasty. A randomized double-blind prospective study of treatment
      time.
AB  - We determined the efficacy and the minimum treatment time necessary for
      prophylaxis with nonsteroidal anti-inflammatory drugs (NSAIDs) for periarticular
      heterotopic ossification (HO) after total hip arthroplasty (THA). Using a double
      blind placebo controlled design, 144 patients operated on with total hip
      arthroplasty for primary arthrosis were treated postoperatively with (1)
      ibuprofen for 3 weeks, (2) ibuprofen for 1 week and placebo for the next 2 weeks
      or (3) placebo for 3 weeks. Radiographic occurrence of periarticular heterotopic
      ossification and complications of the treatment were recorded for the first year.
      Both ibuprofen-treated groups showed significantly less HO than the placebo
      treated group. There was no difference in HO between the patients treated for 8
      or 21 days postoperatively. Both 8 and 21 days of treatment with ibuprofen
      following THA effectively prevents clinically significant degrees of HO. No
      serious short-term complications of the treatment were noted.

PMID- 9602765
TI  - Preoperative irradiation for prophylaxis of ectopic ossification after hip
      arthroplasty. A randomized study in 62 hips.
AB  - 62 hips in 57 patients who were all considered to be at risk for ectopic bone
      formation were randomly divided into two groups: one control group and one group
      who received single dose radiotherapy of 5 Gy at the operation field
      preoperatively. With a mean follow-up of 2.5 years, the incidence of heterotopic
      ossification in the control group was 16 of the 19 hips and in the irradiated
      group 6 of the 43 hips (p = 0.001).

PMID- 9602766
TI  - EBRA improves the accuracy of radiographic analysis of acetabular cup migration.
AB  - EBRA (Ein Bild Rontgen Analyse) is a new computerized method measuring migration
      and wear of the acetabular cup, suggested to improve measurement accuracy. We
      evaluated possible errors of measurement and compared EBRA with standard methods.
      1. We did repeated measurements on a single radiograph using the same reference
      lines. The reliability of the input procedure with standard measurements was
      significantly better than repeated digitization with EBRA. 2. In a more clinical
      test, a group of 10 patients was studied. 5 radiographs were taken of the same
      patient on the same day. EBRA improved the reliability of repeated radiographic
      examination significantly for migration measurements in the vertical direction.
      3. To assess the inter- and intraobserver variations, repeated measurements were
      performed on the clinical series of pelvic radiographs of 10 patients. EBRA was
      significantly better than standard methods. With EBRA, errors of wear and
      migration measurements could be reduced, as compared to standard methods. The
      major improvement with EBRA was found for migration measurements in the vertical
      direction.

PMID- 9602767
TI  - Decreased levels of IGF binding protein-3 in serum from children with Perthes'
      disease.
AB  - The concentrations of insulin-like growth factor (IGF)-I and IGF-binding protein
      (IGFBP)-3 in serum obtained from 27 children with Perthes' disease and 10 age
      matched control subjects were measured by radioimmunoassay (RIA). IGFBPs were
      also analyzed by a Western ligand blotting (WLB) method. The bone age was
      determined in 18 patients from hand-wrist radiographs. Serum levels of IGFBP-3
      but not IGF-I were significantly lower than those in normal controls. WLB showed
      a decrease in the intensity of the IGFBP-3 band in 19 of the 27 patients. The
      bone age was delayed, 2 years or more compared with the chronological age in 7 of
      18 patients, and all of them, except 1, showed decreased levels of IGFBP-3 on
      WLB. We conclude that there may be disturbances in availability of IGFs in some
      patients with Perthes' disease.

PMID- 9602768
TI  - Modified Chiari osteotomy for arthrosis after Perthes' disease. 14 hips followed
      for 2-12 years.
AB  - Between 1983 and 1995, a modified Chiari pelvic osteotomy was performed for
      coxarthrosis after Perthes' disease in 13 patients (14 hips). The median age at
      operation was 33 (16-56) years. The median duration of follow-up was 6 (2-12)
      years. The center-edge angle, Sharp's angle, acetabulum head index and acetabular
      edge angle improved substantially. The median hip score substantially improved
      from 76 (46-90) points to 91 (71-100) points at the most recent follow-up
      examination. We recommend this procedure for patients who have early arthrosis,
      acetabular dysplasia, pain and good range of motion.

PMID- 9602769
TI  - Cumulative revision rate with the Scan Hip Classic I total hip prosthesis. 1,660
      cases followed for 2-12 years.
AB  - We analyzed the cumulative revision rate in 1,474 patients (1,660 hips) operated
      on with a cemented Scan Hip Classic I prosthesis from November 1983 to January
      1994 at Lund University Hospital. The revision rate was analyzed for 3 diagnoses-
      arthrosis, rheumatoid arthritis and complication after a hip fracture--and for 2
      head diameters--22 and 32 mm. Until January 1996, 36 hips were revised: 31
      because of aseptic loosening, 3 because of dislocation and 2 because of
      infection. The overall revision rate was 5.6% after 10 years and was similar in
      arthrosis, rheumatoid arthritis and fracture cases. Due to revisions because of
      dislocation in the 22 mm group, the total revision rate was lower in the 32 mm
      group (p = 0.03).

PMID- 9602770
TI  - Choice of implant for internal fixation of femoral neck fractures. Meta-analysis
      of 25 randomised trials including 4,925 patients.
AB  - We reviewed all randomised trials comparing different implants for treating
      intracapsular fractures of the hip and, where possible, the data were combined.
      25 randomised trials were identified involving 4,925 patients. Screws appeared to
      be superior to pins. It was not possible to determine the optimum number or type
      of screws. No advantage was shown for an implant with a side-plate.

PMID- 9602771
TI  - Thromboembolic complications after arthroscopic knee surgery. Incidence and risk
      factors in 101 patients.
AB  - Deep venous thrombosis (DVT) and pulmonary embolism (PE) are less common after
      knee arthroscopy than after elective hip and knee arthroplasties. There is no
      consensus on the optimal prophylaxis. In this prospective cohort study, we used
      ultrasound, phlebography and lung scan pre- and postoperatively to assess the
      incidence of thromboembolic complications in 101 consecutive patients who
      underwent knee arthroscopy. Preoperatively, patients were screened for typical
      risk factors for DVT such as age, obesity, varicose veins, contraceptive pills
      and nicotine abuse. All patients received a once-daily injection of 5000 IU of
      low molecular weight heparin, at least 12 hours prior to surgery. 5 weeks after
      surgery, the same screening tests were repeated. In 12 of the 101 patients either
      DVT or PE was diagnosed. DVT occurred in 8 cases, 4 of which were silent and 4
      symptomatic. The number of PEs was 9, 8 silent and 1 symptomatic. We found no
      correlation between DVT or PE and individual clinical risk factors, but there was
      a tendency towards the development of DVT and PE, with a higher number of risk
      factors. We found no correlation between DVT and intraoperative risk factors such
      as use of a tourniquet, type of anesthesia or duration of surgery. The relatively
      high rate of thromboembolic events after knee arthroscopy in our study suggests
      the need of all patients for routine use of thromboprophylaxis, probably in a
      higher dose than given.

PMID- 9602772
TI  - Open wedge tibial osteotomy by callus distraction in gonarthrosis. Operative
      technique and early results in 36 patients.
AB  - Proximal tibial osteotomy is indicated in cases of medial gonarthrosis with varus
      deformity in the active, younger patient. We report our experience of the
      hemicallotasis technique in 36 patients and the early clinical results after a
      median follow-up of 14 (11-16) months. The median patient age was 54 (33-64)
      years. The median hip-knee-ankle (HKA) angle was 172 (161-179) degrees
      preoperatively, 184 (178-187) degrees after completed correction and 183 (175
      190) degrees at follow-up. The median fixation time was 88 (61-146) days.
      Complications were minor. Superficial pin-site inflammation/infections occurred
      in one fifth of the pins. The HSS score increased from a median 71 preoperatively
      to 94 at follow-up, the Lysholm score from 56 to 91 and the Tegner activity score
      from 6 to 10. The Nottingham Health Profile showed significant improvements as
      regards pain and physical mobility.

PMID- 9602773
TI  - Elevated levels of synovial fluid PLA2, stromelysin (MMP-3) and TIMP in early
      osteoarthrosis after tibial valgus osteotomy in young beagle dogs.
AB  - We determined the concentration of markers in cartilage and synovium metabolism
      in the synovial fluid (SF) of the knee of young beagle dogs with slowly
      progressive osteoarthrosis. Osteoarthrosis (OA) was induced by a tibial 30
      degrees valgus osteotomy to the right hindlimb of 16 dogs. The contralateral knee
      served as control. The animals were killed 7 (group I) and 18 months (group II)
      after operation. The levels in SF of chondroitin sulfate (CS), tissue inhibitor
      of metalloproteinases (TIMP-1), stromelysin (MMP-3), hyaluronan (HA), and the
      activity of phospholipase A2 enzyme (PLA2) were assayed. The first microscopic
      signs of cartilage degeneration were observed 7 months postoperatively and the
      lesions became more severe, including osteophyte formation during the following
      11 months. The synovial fluid level of MMP-3 was higher (p = 0.04) at both time
      points in the knee joint of the operated hindlimb than in the contralateral
      joint. On the operated side, 7 months postoperatively, synovial fluid PLA2
      activity was higher (p = 0.02) than in the contralateral knee joint, but not 18
      months postoperatively. The SF level of TIMP-1 was higher (p = 0.04) in the
      operated joint than in the contralateral joint 18 months after operation. The
      molar ratio of MMP-3 to TIMP-1 was higher (p = 0.001) in group II than in group
      I. The changes observed in the concentration of synovial fluid markers in this
      slowly progressive canine OA model suggest that activation of an inflammation
      related process occurs at an early stage of the OA disease induced by unilateral
      tibial valgus osteotomy.

PMID- 9602774
TI  - Lateral release and proximal realignment for patellofemoral malalignment. A
      prospective study of 40 knees in 36 adolescents followed for 1-8 years.
AB  - We performed lateral release and proximal realignment for painful patellofemoral
      malalignment in 36 adolescents (40 knees), with a mean age of 14 (9-16) years.
      The mean follow-up was 4 (1-8) years. The subjective outcome was excellent in 20
      knees, good in 13, fair in 5, and poor in 2. The mean radiographic correction of
      the lateral patellar shift was 75%, and of the tilting angle of the patellar 27%.
      There was a positive association between the realignment effect and the
      subjective outcome.

PMID- 9602775
TI  - MRI evaluation of the inferior glenohumeral ligament. Comparison with
      arthroscopic findings in 81 shoulders.
AB  - Arthroscopic Bankart repair, using staples, requires a thick and wide anterior
      band of the inferior glenohumeral ligament. We compared MRI and arthroscopic
      findings of the ligament in 81 shoulders with traumatic anterior glenohumeral
      instability. When fluid was present in the shoulder, sensitivity and specificity
      of the MRI evaluation for the presence of a thick and wide ligament were 82% and
      100%, respectively. In shoulders without joint fluid, the condition of the
      ligament was evaluated according to the presence of a low- or moderate-signal
      triangle structure on the anterior margin of the glenoid cavity in the 3 MR
      images obtained from the inferior 2 cm of the glenoid. Sensitivity and
      specificity of the MRI evaluation in cases without fluid were 84% and 93%,
      respectively. The MR technique needs to be further improved to achieve better
      sensitivity for preoperative selection of shoulders suitable for Bankart repair
      with staples.

PMID- 9602776
TI  - Percutaneous treatment of trigger finger. 34 fingers followed 0.5-2 years.
AB  - We performed percutaneous A1 pulley release on 34 trigger fingers in 30 patients
      with an angiocath needle. Complete release was achieved in all fingers. There
      were no complications and no recurrences during mean 0.5 (1-2) years follow-up.

PMID- 9602777
TI  - Zoned exponential, vertical and horizontal ultra-clean laminar airflows. No
      differences in bacteriological efficiency.
AB  - We compared the novel zoned exponential ultra-clean operating room ventilation,
      needing no extra side-walls with the traditionally used ultra-clean air systems
      having vertical or horizontal laminar airflow, but requiring extra side-walls.
      The three units were evaluated with regard to elimination of particles with focus
      on airborne and sedimenting bacteria-carrying particles (colony forming units,
      cfu) during rigidly standardized sham operations. Although minor differences were
      recorded inside the ultra-clean airflows, the three systems were comparable with
      regard to bacteriological efficiency and ensured a low air and surface
      contamination (0.05-4 cfu/m3 and 7-72 cfu/m2/h, depending on the site of
      sampling). We conclude that all three systems fulfilled well the criteria for
      ultra-clean air (< 10 cfu/m3), but that exponential airflow is the most versatile
      alternative, as additional side-walls around the operating area can be omitted.

PMID- 9602778
TI  - Ethene oxide and bone induction. Controversy remains.
AB  - There is controversy as to whether ethene oxide ("ethylene oxide", EO)
      sterilization destroys the bone-inducing capacity of demineralized bone matrix
      (DBM) or not. Correctly performed studies seem to support both opinions. Bone
      conductive properties of fresh frozen, defatted bone grafts are greatly impaired
      by EO sterilization, whereas purified inductive proteins resist EO. Studies
      showing destruction of osteoinductive capacity used nonpulverized DBM, whereas
      the others used powder. This could be the key to resolving the controversy,
      because if EO treatment reduces the cells' ability to penetrate a cortical graft
      and to reach inductive proteins inside it, it may appear noninductive after EO
      sterilization, even though BMP molecules may be intact. On the other hand, cells
      could easily penetrate the powder implants. We compared the effect of EO
      sterilization on the inductive capacity of demineralized cortical bone with that
      of DBM powder, using allogeneic material in rats. Cortical pieces lost all
      inductive capacity by EO sterilization, whereas the powder yielded a calcium
      content which was at best one fourth of the unsterilized. The concentrations of
      residual EO, ethene chlorohydrin and ethene glucol at implantation were far below
      approved levels. Another difference between studies is the humidity during EO
      treatment. In our hands, humidification reduced bone yield by half. In
      conclusion, EO sterilization may impair the biological performance of bone
      inductive implants by reducing cell penetration into bulk material. However, DBM
      powder, when correctly sterilized, also yielded scanty amounts of bone.

PMID- 9602779
TI  - Effects of lesion between bone, periosteum and muscle on fracture healing in
      rats.
AB  - We assessed the effects of periosteal detachment from bone and musculature on the
      healing of diaphyseal fracture. In 30 male Wistar rats we produced a partial
      osteotomy, which was manually broken in the middiaphysis of the left femur. All
      fractures were reamed and stabilized with an 1.6 mm steel pin. The animals were
      randomly assigned to 3 groups. In group 1, a subperiosteal detachment between
      cortex and periost was created in the middle third of the diaphysis. An
      extraperiosteal detachment between periost and the surrounding musculature was
      performed in group 2. In group 3, the periosteum was isolated from the
      musculature by an extraperiosteal detachment and application of an e-PTFE sheath
      (Gore-Tex expanded polytetrafluoroethylene) around the shaft between the periost
      and the surrounding muscles. The rats were killed after 4 weeks and callus
      formation and mechanical characteristics were measured. All fractures healed by
      production of external callus. The callus area was significantly less in the
      group where periost was mechanically isolated from the surrounding muscles
      compared to the other groups. Bending moment, bending rigidity and fracture
      energy were less in this group than in groups 1 and 2. No differences were
      detected between the sub- and extraperiosteal groups, either in callus formation
      or in mechanical measurements. Our findings underline the importance of the
      muscle-periosteal connection for periosteal healing of diaphyseal fractures.

PMID- 9602780
TI  - Digital image analysis of bone allograft union in sheep.
AB  - We compared the reliability of computer-assisted radiographic analysis (CARA) and
      visual evaluation of radiographs to assess host-graft junctions. 68 host
      bone/allograft junctions were obtained from an ongoing study on bone allografting
      in sheep. At 6 months, the grafted tibias were explanted and healing of the host
      graft junctions were macroscopically determined. 49 junctions were
      macroscopically healed, whereas 19 had not united. 51 (0.8) of the junctions were
      correctly classified by radiographs, while 63 (0.9) of the junctions were
      correctly classified by CARA (p = 0.03). These findings warrant further
      evaluation in a clinical setting.

PMID- 9602782
TI  - Bone mineral density assessed by quantitative ultrasound and dual energy X-ray
      absorptiometry. Normative data in Malmo, Sweden.
AB  - We measured bone mineral density (BMD) in 128 men and 143 women, aged 22-90, by
      dual energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS). We
      found reduced bone mineral density in relation to age as measured both by DEXA
      and QUS. There was a correlation between 0.28 and 0.52 in men and between 0.53
      and 0.77 in women when comparing DEXA and QUS measurements. When including only
      persons with low bone mass, the correlation was less.

PMID- 9602781
TI  - Serum CRP and IL-6 levels after trauma. Not predictive of septic complications in
      31 patients.
AB  - We studied 31 blunt trauma victims, Injury Severity Score (ISS) mean 14 (9-57),
      for the pattern of release of C-reactive protein (CRP) and cytokine interleukin-6
      (IL-6). Blood samples were taken on admission (within 6 hours of injury), as well
      as at 24 hours, and 3, 5 and 7 days. Serum CRP and IL-6 were measured by ELISA.
      Subsequent surgical events and sepsis were noted. Serum IL-6 levels on admission
      were considerably higher (median 135 pg mL-1) than our laboratory reference range
      (< 5 pg mL-1), slowly returning towards reference values during the study. Serum
      CRP levels were similar to laboratory normal values on admission (median 8.5 mg L
      1 vs 7.5 mg L-1), reaching peak values (median 110 mg L-1) after 3 days. There
      was a correlation between IL-6 release and ISS but not between CRP and ISS.
      Patients undergoing surgery showed further increases in IL-6 and CRP levels
      postoperatively. Of 24 surgical patients, 9 developed postoperative sepsis. In
      blunt trauma patients, early assessment of the markers CRP or IL-6 were not
      useful for the diagnosis of sepsis. Levels of CRP following accidental or
      surgical trauma should be assessed with caution.

PMID- 9602783
TI  - A proximal humeral fracture, complicated by a pseudoaneurysm--a case report.

PMID- 9602784
TI  - Spontaneous bilateral hip fractures in a patient with steroid-induced
      osteoporosis--a case report.

PMID- 9602785
TI  - Massive osteolysis in the pelvis--a case report.

PMID- 9602786
TI  - Restoration of the mechanical axis of the lower limb--a case report of
      perichondrium grafting of the medial femoral condyle.

PMID- 9602787
TI  - Monstrous congenital macrodactyly with syndactyly of the foot--a case report.

PMID- 9602789
TI  - Molecular control of nephrogenesis and the pathogenesis of kidney malformations.

PMID- 9602788
TI  - Pigmented villonodular synovitis.

PMID- 9602790
TI  - Prenatally detected uropathy: epidemiological considerations.

PMID- 9602791
TI  - Upper urinary tract obstruction: experimental and clinical aspects.

PMID- 9602792
TI  - Lower urinary tract obstruction: clinical and experimental aspects.

PMID- 9602793
TI  - Development of glomerular filtration and tubular sodium reabsorption in the human
      fetus and newborn.

PMID- 9602794
TI  - Prenatally diagnosed hydronephrosis: the Great Ormond Street experience.

PMID- 9602795
TI  - Effects of medullary nailing on the normal blood supply of diaphyseal cortex.
      1973.

PMID- 9602796
TI  - Update on the management of open fractures of the tibial shaft.
AB  - A retrospective study of 133 open tibial fractures in 129 patients treated at the
      Hennepin County Medical Center between 1986 and 1993 was done. The results of the
      treatment protocol in this patient group is presented and the current
      classification schemes, prevention of infection, debridement, antibiotics, soft
      tissue reconstruction, fracture stabilization methods, bone grafting, and
      exchange nailing are discussed. Recent studies that have documented interobserver
      disagreement in the classification of open fractures underscore the difficulties
      encountered in the initial assessment and treatment of open tibial shaft
      fractures. Despite repetitive and aggressive debridement, a certain number of
      fractures will remain contaminated and become infected. Infection after these
      severe injuries is probably multifactorial, and its prevention requires that the
      surgeon diligently adhere to the imperatives of open fracture care.

PMID- 9602797
TI  - Retrograde nailing of humeral shaft fractures.
AB  - The use of intramedullary nailing in the upper extremity is still controversial.
      Those who have experience with antegrade nailing have either great enthusiasm or
      strong criticism for the procedure. Criticism of the procedure is because of the
      trauma that can occur to the rotator cuff and possible impingement syndrome,
      which can occur after antegrade nail insertion. The technique of retrograde nail
      insertion with the unreamed humeral nail is described in detail. In a series of
      190 retrograde nailings performed in a prospective multicenter study, the most
      frequent intraoperative problems were fissure or avulsion at the entry portal (n
      = 8; 4.2%) and secondary radial nerve palsy (n = 8; 4.2%). All radial nerve
      palsies recovered spontaneously. Sixty-eight patients were followed up until the
      fractures healed. There were five (7.4%) bone healing problems. Four of five
      could be solved with use of the unreamed humeral nail in a second operative
      procedure, whereas the fifth bone healing problem required plate osteosynthesis.
      Function of the shoulder and elbow joint was excellent in 89.7% and 88.3% of the
      patients, respectively. Retrograde humeral nailing is a safe and reliable
      procedure if done properly. It is a valuable stabilization technique for acute
      and pathologic fractures and for pseudarthrosis. Bone healing problems after
      unreamed humeral nailing must be analyzed individually, but they can be treated
      with the same implant in combination with cancellous bone grafts, reaming,
      additional hardware, or intrafragmentary compression.

PMID- 9602798
TI  - Antegrade interlocking nailing of acute humeral shaft fractures.
AB  - Between 1992 and 1996, 73 acute humeral shaft fractures in 71 patients were
      treated with antegrade Russell-Taylor humeral nailing. Sixty (84%) patients
      sustained multiple trauma, and 26 (36%) fractures were open. Three patients had
      preoperative brachial artery injuries, and 12 had preoperative nerve palsies.
      Sixty-nine (94.5%) fractures united primarily, and two additional fractures
      united after bone grafting. There were no infections. Two (2.7%) iatrogenic
      radial nerve palsies occurred, and both were transient. Full shoulder function
      returned in 66 (90%) patients. Two (2.7%) patients had impingement from proximal
      locking screws, and one (1.4%) had impingement from a prominent nail. Normal
      elbow function was regained in 96% of patients. All patients without full return
      of elbow and shoulder function had concomitant injuries. Antegrade Russell-Taylor
      nailing is an acceptable alternative for the treatment of acute humeral shaft
      fractures in multiply injured patients.

PMID- 9602799
TI  - Treatment of pathologic fractures of the humerus with Seidel nailing.
AB  - A retrospective study is presented of 14 patients with pathologic fractures of
      the humerus (12 established, two impending) treated with Seidel nailing from 1988
      through 1995 in the authors' institution. There were nine women and five men
      whose average age was 59.5 years. Breast, prostate, and kidney hypernephroma
      accounted for the majority of the primary lesions. All but one lesion were
      located in the middle shaft of the humerus. Ten lesions were considered large (>
      5 cm long). In five cases an open curettage and allografting were done. Early
      pain relief was successful in 85% of the patients. The worst complication found
      was definite nerve palsy in two (14.28%) patients. Ten fractures healed and two
      failed to heal. Two thirds of the patients had good functional results. The
      average survival was 12 months. Intramedullary fixation of pathologic fractures
      improves the quality of life by controlling pain for most patients.

PMID- 9602800
TI  - Use of the Gamma nail in the treatment of fractures of the proximal femur.
AB  - Fractures of the proximal femur are, more than ever, an important challenge in
      the field of traumatology. The Gamma nail, a combination of advantages of the
      sliding screw with the intramedullary nail, represents an efficient technique in
      the management of these fractures. A series of 224 fractures of the proximal
      femur in which this nail was used is reported. The average age of the patients
      was 79.2 years. The mean healing time was 68.2 days in 99.4% of the cases. The
      incidence of perioperative complications was 10.3% showing that, in most of the
      cases, the complications occurred because of poor technique. Postoperative
      complications occurred with an incidence of 14.1%. Seven cases of migration of a
      proximal screw, six shaft fractures, and one broken nail were the most important
      complications. The device allowed for early mobilization and full weightbearing
      of the affected hip regardless of the type of fracture. With adequate surgical
      technique and experience, the advantages of the Gamma nail increases as the
      complication rate diminishes.

PMID- 9602801
TI  - Indications for use of the long Gamma nail.
AB  - A retrospective analysis of 42 patients treated by intramedullary nailing with
      the Gamma nail with a mean followup of 22.4 months is reported. The indications
      for the use of this nail were subtrochanteric fractures in 31 cases, diaphyseal
      femoral fractures in 10 cases, and segmental fracture in one case. Seven cases of
      the diaphyseal fractures were renailings for a previously placed nail. There was
      one pathologic fracture in the subtrochanteric group and three in the diaphyseal
      group. The indications of this new technique and its complications are analyzed.

PMID- 9602802
TI  - Interlocked intramedullary nailing for treatment of open femoral shaft fractures.
AB  - Twenty-eight patients with open femoral shaft fractures treated by reamed
      intramedullary nailing were reviewed retrospectively. Nine patients had Gustilo
      Grade I injuries; 14, Grade II; and five, Grade IIIA. Twenty cases had static
      locking, two cases had dynamic locking, and six cases were not locked. Average
      time to union was 20 weeks. The infection and nonunion rates were 0%. The data
      suggest that interlocked reamed intramedullary nailing is a safe treatment option
      for treating open femoral shaft fractures.

PMID- 9602803
TI  - Antegrade nailing for fractures of the distal femur.
AB  - Thirty-five fractures of the distal femur were treated by antegrade
      intramedullary nailing. All of the fractures were treated by a closed technique.
      In the cases in which there was extension of the fracture to the knee joint, the
      fracture initially was stabilized with percutaneous lag screws. Four patients
      died before fracture healing was complete and 11 were lost to followup. There
      were 14 extraarticular (Type A) and six intraarticular (Type C1 and Type C2)
      fractures. All of these fractures healed in a mean time of 17.27 weeks.
      Functional outcome using the Hospital for Special Surgery knee score was 87.
      Complications were infrequent with one (5%) pseudarthrosis and no infections.
      Although this is a very demanding technique, antegrade intramedullary nailing is
      an efficient procedure compared with other methods of open reduction and internal
      fixation for difficult distal femoral fractures.

PMID- 9602804
TI  - Retrograde intramedullary nailing of supracondylar femoral fractures.
AB  - As an alternative to standard AO/Association for the Study of Internal Fixation
      plate and screw techniques, retrograde intramedullary locked nailing of
      supracondylar and intracondylar (AO/Association for the Study of Internal
      Fixation Type 33) fractures is reviewed. This includes a historic review, the
      technique for knee arthrotomy, fracture reduction and nail insertion, and the
      reported clinical and biomechanical results. The retrograde intramedullary locked
      nail is a viable alternative for the treatment of AO/Association for the Study of
      Internal Fixation Type 33-A and some C supracondylar femoral fractures and should
      be part of the internal fixation armamentarium, however, it does not replace the
      standard biologic plate and screw techniques for most fractures.

PMID- 9602805
TI  - Intramedullary nailing of femoral fractures in adolescents.
AB  - A prospective study of adolescents with femoral fractures treated with
      intramedullary nailing was done to identify complications and evaluate the
      outcome of this method of treatment. Sixty patients with femoral fractures have
      been treated with antegrade intramedullary nailing. Magnetic resonance imaging
      scans were obtained to evaluate for subclinical avascular necrosis of the femoral
      head. The average patient age was 12 years. All patients had open physes at the
      time of surgery. Implants were removed in 33 patients to date at an average of 10
      months after initial nailing. All but two patients continue to have no signs of
      avascular necrosis, no rotational or angular deformity, and no nerve palsy. Two
      patients have had subclinical avascular necrosis as seen on magnetic resonance
      imaging. One patient had avascular necrosis develop in both femoral heads 1 year
      after nail removal from the right femur. The second patient has asymptomatic
      marrow changes on magnetic resonance imaging consistent with avascular necrosis
      with no femoral head collapse. It is thought that intramedullary nailing of
      pediatric femoral fractures is a safe treatment option. Few complications and a
      small risk of subclinical presentation of avascular necrosis of the femoral head
      that can become evident after removal of the implant have been found.

PMID- 9602806
TI  - Local or free muscle flaps and unreamed interlocked nails for open tibial
      fractures.
AB  - The treatment of open tibial fractures associated with severe soft tissue
      injuries remains a difficult dilemma, even to the experienced fracture surgeon.
      To ascertain the efficacy of nailing tibial fractures with severe soft tissue
      injuries, a review of all open tibial fractures treated at the authors'
      institution was done. Those fractures initially stabilized with nonreamed nails
      which required muscle flaps for coverage were selected for study. Thirty-three
      patients (26 men, seven women) were treated with intramedullary nailing and
      muscle flap coverage for the soft tissue defects. The average length of followup
      was 12.1 months (range, 7-42 months). The average time to union was 27 weeks
      (range, 14-45 weeks). There were five (15%) infections: two (6%) superficial
      wound infections, one (3%) flap infection, and two (6%) cases of osteomyelitis.
      In no patient did the infection result in limb ablation. Thirteen of 33 (42%)
      patients required secondary procedures to enhance union. In this study, it was
      found that although delayed procedures frequently were required to promote
      fracture union, the time to union, and infection rates were not significantly
      different from those reported for external fixation of fractures that require
      local or free muscle transfers.

PMID- 9602807
TI  - Nonreamed flexible locked intramedullary nailing in tibial open fractures.
AB  - Thirty-nine open unstable tibial shaft fractures were treated with a nonreamed
      flexible locked intramedullary nail between 1992 and 1995. There were 23 Grade I,
      12 Grade II, three Grade IIIA, and one Grade IIIB fractures. The average time of
      followup assessment was 24 months. The average time to fracture union was 24
      weeks. Complications were related in most cases to fractures with highly unstable
      patterns and extensive soft tissue lesions. There were five (12.5%) delayed
      unions and one (2.5%) nonunion. Deep infections developed in three (7.7%)
      patients. One patient required an additional procedure to correct a varus
      malunion. There were no implant failures. It was concluded that nonreamed
      flexible locked nailing provides effective control of axial and rotational
      stability in unstable Grades I to IIIA open fractures with acceptable union rates
      and a low incidence of complications secondary to the fixation system.

PMID- 9602808
TI  - Unreamed nailing of tibial fractures with the solid tibial nail.
AB  - In 1993 a solid 7.5-mm tibial nail was developed and is composed of a wrought
      stainless steel alloy. In a preclinical testing series its static and dynamic
      mechanical properties proved to be superior to other small diameter nails. The
      clinical application of the Solid Tibial Nail in 70 cases of acute tibial
      diaphyseal fractures showed promising results. Neither severe intraoperative
      complications nor infections were observed. The entire series, including seven
      Grade I, eight Grade II, four Grade IIIA, and nine Grade IIIB open fractures,
      revealed a union rate of 95% at 6 months postoperative. After dynamization in one
      case and reaming and renailing in three cases, the fractures with delayed healing
      progressed to union within the following 3 months. There was no need for bone
      grafting in any of the cases. Locking screw breakage was observed in 10 (14%)
      cases 8 to 24 weeks postoperatively. This did not lead to any additional
      complications. No nail failures were observed. The excellent results of unreamed
      nailing with the Solid Tibial Nail consequently led to its use as the primary
      method of treatment for tibial fractures associated with soft tissue injury at
      the authors' institution.

PMID- 9602809
TI  - Latissimus dorsi pedicled graft. An unusual cause of shoulder pain.
AB  - An unusual complication after the use of a pedicled latissimus dorsi flap is
      reported. The flap was used to reconstruct a facial defect after excision of a
      high grade mucoepidermoid carcinoma of a parotid gland. The tendinous insertion
      of the latissimus dorsi on the humerus was left intact and the flap pivoted
      around this point. Subsequent use of his arm caused the patient disabling
      shoulder pain from traction on the tendon. Symptoms resolved after the tendon was
      divided.

PMID- 9602810
TI  - The humeroscapular motion interface.
AB  - Motion between the humerus and scapula commonly is described as glenohumeral
      motion. However, humeroscapular motion occurs at two distinct sites. In addition
      to the motion at the diarthrodial glenohumeral joint, movement occurs between the
      proximal humerus and related structures and the surrounding sleeve of structures,
      including the acromion, deltoid, coracoid, coracoacromial ligament, and the
      muscles attached to the coracoid. This site of nonarticular shoulder motion is
      defined as the humeroscapular motion interface. Nonarticular humeroscapular
      motion can be documented and measured using standard magnetic resonance imaging
      techniques. The maximum average interfacial motion using axial images was 29.1
      mm, which occurred at the level of the maximum diameter of the humeral head.
      Interfacial motion varied depending on the site measured. If pathologic
      conditions such as adhesions secondary to trauma or surgery interfere with or
      obliterate this space at sites of significant sliding motion, overall shoulder
      motion will be limited. Successful treatment of shoulder stiffness related to
      humeroscapular restraints is likely to require restoration of the normal sliding
      motion at the humeroscapular motion interface, in addition to resolving
      restraints affecting the glenohumeral joint motion.

PMID- 9602811
TI  - The fate of pelvic osteolysis after reoperation. No recurrence with lesional
      treatment.
AB  - Twenty-three hips (21 patients) with 30 pelvic osteolytic lesions underwent
      reoperation and were observed prospectively for 25 to 74 months (average, 40
      months) to assess the fate of pelvic osteolysis after reoperation. The average
      radiographic dimensions of the lytic lesions were 2.4 x 1.9 cm with the largest
      lesion measuring 7 x 5 cm. The porous ingrowth acetabular component shell had
      been left in situ in 15 hips and had been revised in eight. There was no
      difference in the average lesional size for hips with revised shells compared
      with those with unrevised shells. In cases where the shell was left in situ, the
      osteolytic lesions were curetted by working around the component perimeter or
      through holes in the shell. In 18 hips the bone defect(s) were grafted with
      autograft or allograft. Regardless of the management of the acetabular shell or
      the absence or presence of bone graft, none of the osteolytic lesions have
      progressed. Twenty-six of the 30 lesions have increased radiographic density. All
      acetabular components remain radiographically well fixed. There were no new
      osteolytic lesions. All hips were functioning well, and none have required
      subsequent reoperation for any reason. There was a statistically significant
      reduction in the operative time and the amount of blood loss when the acetabular
      component was not revised. It does not appear necessary to remove a well fixed
      and well positioned cementless acetabular component for the treatment of pelvic
      osteolysis. Debridement of periarticular inflammatory tissue and lesional
      curettage, either with or without bone graft, is effective in managing this type
      of bone loss. Revision of the acetabular component shell was associated with a
      significant increase in operative time and blood loss. These results support
      routine radiographic evaluation after total hip arthroplasty to monitor the
      development of osteolysis. On the basis of this experience, the authors recommend
      lesional treatment of progressive pelvic osteolysis to avoid more difficult
      surgery and minimize patient morbidity.

PMID- 9602812
TI  - Porous hip replacement in Paget's disease. An 8-2/3-year followup.
AB  - An 8-year 8-month followup of a now 78-year-old active woman with a painful,
      severe varus deformity of the femur and arthritis of the right hip associated
      with monostotic Paget's disease of the hip is presented. Treatment consisted of
      multiple osteotomies, followed by implantation of a long stemmed cobalt chrome
      fully coated porous ingrowth hip system. The patient had an excellent outcome,
      including relief of pain and restoration of excellent function, despite ongoing
      severe osteolytic changes that did not appear to influence the healing of the
      osteotomies or the clinical stability of the implant.

PMID- 9602813
TI  - Early catastrophic tibial component wear after unicompartmental knee
      arthroplasty.
AB  - Unicompartmental knee arthroplasty is an appropriate method of treating selected
      patients with osteoarthritis of the medial compartment of the knee. The common
      causes of failure are aseptic loosening, infection, patellofemoral pain, and
      deterioration in the opposite compartment. Seven cases of a cohort of 32 Robert
      Brigham unicondylar knee replacements that failed because of early catastrophic
      wear of the polyethylene tibial component are reported. Possible reasons
      suggested for failure include inadequate thickness of polyethylene, fusion
      defects in the polyethylene structure as a result of the sterilization process,
      increased rotational freedom, and reduced conformity in the design of the
      prosthesis.

PMID- 9602814
TI  - Long-term prognosis after healed amputation in patients with diabetes.
AB  - In this prospective study, mortality, rehabilitation, and new amputations on the
      same or on the contralateral leg were studied in 189 patients with diabetes who
      had achieved healing of an index amputation. Ninety-three patients had achieved
      healing after an index minor (below the ankle) and 96 after an index major (above
      the ankle) amputation, precipitated by a foot ulcer. The healing time was 29
      weeks (range, 3-191 weeks) with a minor amputation and 8 weeks (range, 3-104
      weeks) with a primary major amputation. The mortality 1, 3, and 5 years after the
      index amputation was 15%, 38%, and 68%, respectively, and was higher in patients
      who had achieved healing after major amputation than in patients achieving
      healing after minor amputation. The rate of new amputations after 1, 3, and 5
      years of observation was 14%, 30%, and 49%, respectively. There was no difference
      among patients with an index minor and those with an index major amputation. The
      rate of new major amputations was 9%, 13%, and 23%, respectively, and was higher
      in patients with an index major amputation. Eighty-five percent of new
      amputations were precipitated by a foot ulcer. Patients living independently
      before the index amputation returned to living independently more often after a
      minor than a major amputation (93% versus 61%). One year after the index
      amputation, 70% of patients who had achieved healing after having a minor
      amputation and who could walk 1 km or more before amputation had regained this
      walking capacity, compared with 19% of patients having a major amputation.
      Seventy percent of patients with an index transtibial amputation who could walk
      before amputation were fitted with a prosthesis, and 52% were using it regularly.
      Patients with diabetes who had an index major amputation had a higher mortality,
      an equal rate of new amputation, and a lower rehabilitation potential than did
      patients who had an index minor amputation.

PMID- 9602815
TI  - Reliability of the peroneal latency in normal ankles.
AB  - The aim of this study was to determine the reliability of peroneal latency
      between trials and to compare the right and left sides in healthy subjects. A
      dual platform trapdoor was constructed to tilt the right or the left ankle by 30
      degrees in the frontal plane. Electromyography recorded the onset of peroneal
      activity in response to this perturbation, and an accelerometer detected the
      onset of trapdoor movement. Peroneal latency was determined algorithmically as
      the time difference between the onset of trapdoor movement and the onset of
      peroneal activity. Twenty trials were recorded from 31 right leg dominant,
      healthy subjects. Peroneal latency was measured successfully for 613 trials (99%
      success rate). A repeated measures analysis of variance showed a main effect for
      side with the right, dominant side recording a longer latency. Intertrial
      reliability of the peroneal latency was high (intraclass correlation coefficients
      for the right and left legs were .91 and .82, respectively). Thus, peroneal
      latency is a reliable measure of the polysynaptic reflex ares involved in the
      response of these muscles to a sudden inversion stress.

PMID- 9602816
TI  - Tendon transfer for equinovarus deformed foot caused by cerebrovascular disease.
AB  - Surgical correction was performed on 125 patients who had equinovarus deformity
      caused by a cerebrovascular accident and who needed an ankle foot orthosis for
      walking. The operative procedures involved anterior transfer of the long toe
      flexors (flexor hallux longus and flexor digitorum longus; long toe flexor group)
      or lateral transfer of the anterior tibial tendon (anterior tibial tendon group),
      combined with lengthening of the Achilles tendon. On evaluation more than 2 years
      after surgery, 83 of 110 patients of the long toe flexor group and eight of 15
      patients of the anterior tibial tendon group were able to walk without a brace.
      Five patients of the anterior tibial tendon group who had shown strong
      contraction of the anterior tibial muscle during the swing phase before surgery,
      needed a brace because of a drop foot after surgery. Thus, lateral transfer of
      the anterior tibial tendon was abandoned in 1984. Recurrence of varus deformity
      was seen in approximately 15% of the patients in both groups. Anterior transfer
      of the long toe flexors, using them as dorsiflexor tendons or for tenodesis,
      seemed to produce better results.

PMID- 9602817
TI  - Operative treatment of hip fractures in patients with renal failure.
AB  - The conditions of a hip fracture and renal failure cause particularly high
      mortality. Eight patients (average age, 63 years) who had operative treatment for
      nine hip fractures were studied retrospectively. Three had intertrochanteric
      fractures fixed with sliding compression screws, and five had femoral neck
      fractures (bilateral in one patient): two nondisplaced femoral neck fractures
      were fixed with percutaneous screws, and four displaced femoral neck fractures
      were treated with arthroplasties in three and percutaneous screws in one.
      Operative treatment was done when the patient was in medically stable condition
      (average, 8 days). Full weightbearing was allowed on the injured limb after
      surgery. Early morbidity analysis showed no wound infections, thromboembolic
      events, or hemorrhagic complications. The first year mortality was three (38%).
      Late morbidity included one nonunion and one sliding screw penetration. Total
      mortality at 6 years was seven (88%) patients, with an average postoperative
      survival time of 28 months. Preoperative ambulation was preserved in five of
      seven (71%) patients. One the basis of this study, it appears that a team
      approach to operative management including nephrologist and surgeon helps to
      reduce short term complications and mortality and allows such patients to be
      mobilized and regain ambulation.

PMID- 9602818
TI  - Contrast enhanced magnetic resonance imaging for femoral neck fracture.
AB  - Femoral head perfusion was evaluated in 29 patients after acute femoral neck
      fracture using contrast enhanced fat saturation magnetic resonance imaging. The
      patients were followed up with T1 and T2 weighted spin echo magnetic resonance
      imaging without fat saturation, which is suitable in detecting avascular
      necrosis. The mean interval from injury to the initial contrast enhanced fat
      saturation magnetic resonance imaging was 24.5 hours. The mean age at the time of
      injury was 69 years, and the mean followup was 26.9 months. Three distinct
      patterns of femoral head enhancement were recognized in the acute phase after
      fracture. When the whole femoral head was well enhanced (Type 3, n = 11), no
      avascular necrosis developed. In contrast, when the head showed no enhancement
      (Type 1, n = 6), avascular necrosis developed in all patients. In patients with
      partial enhancement (Type 2, n = 12), avascular necrosis developed in five
      patients. These data showed the current method provided an accurate prediction of
      the development of avascular necrosis in the patients with Type 1 and Type 3
      enhancement. However, overall predictive value was 59% (17 of 29 patients)
      because of the uncertainty in the patients with partial enhancement (Type 2), and
      additional study is needed for this method to become routine in clinical use.

PMID- 9602819
TI  - Hindquarter amputation for pelvic tumors. The importance of patient selection.
AB  - Twenty-two patients underwent hindquarter amputation with curative intent for
      malignant or locally aggressive tumors of the pelvis (21 cases) or proximal thigh
      (one case). In all cases, the ilium was resected, and in seven cases an osteotomy
      of the sacrum was done to achieve negative surgical margins. Only six wounds
      healed without complications. The worst wound problems occurred in patients
      requiring ligation of the common iliac vessels and in those requiring a sacral
      osteotomy. Twelve patients have died of disease, two are alive with extensive
      pulmonary metastases, and one remains well after excision of a local tumor
      recurrence. Thirteen of 14 patients with high grade sarcoma had metastases
      develop, compared with only one of eight patients with low grade sarcoma. Eight
      patients (all with high grade sarcoma) died within 1 year of surgery. Seven
      patients have remained disease free at a mean of 39 months after surgery. Given
      the poor prognosis and high morbidity after amputation in high grade sarcoma, the
      authors think that consideration should be given to pursuing nonoperative
      management in patients with large, high grade sarcomas and significant medical
      extension to the sacroiliac joint or sacrum.

PMID- 9602820
TI  - Posttransplantation lymphoproliferative disorder in the knee.
AB  - Lymphoproliferative disorders with primary presentation in a joint are extremely
      rare. Posttransplantation lymphoproliferative disorders are commonly extranodal
      at presentation but rarely involve joint structures. The authors describe a fatal
      case of posttransplantation lymphoproliferative disorder presenting in the knee
      of a 39-year-old woman who had undergone renal transplantation many years before.

PMID- 9602821
TI  - Fluid pressure causes bone resorption in a rabbit model of prosthetic loosening.
AB  - High fluid pressures can be present throughout the effective joint space after
      total hip replacement and can extend locally to the bone implant interface. A new
      experimental implant model was developed to study whether local fluid pressure
      can induce osteolysis at a bone implant interface. Twelve mature rabbits received
      a titanium implant that was allowed to osseointegrate before a fluid pressure of
      150 mm Hg was applied to a specific area of the titanium bone interface in six of
      the animals. Osteolysis occurred in all six implants exposed to the fluid
      pressure. In two of these animals, no measurable flow occurred. In both animals a
      localized osteolytic lesion developed with evidence of osteocyte death in the
      surrounding cortical bone. In four animals, fluid flow away from the lesion
      occurred after several days that corresponded to either the formation of a canal
      through the cortical bone or extended resorption of the surrounding cortical
      bone. In some of these specimens, the microscopic appearance was similar to that
      of prosthetic loosening: high numbers of macrophages were observed containing
      intracellular bone particles. No resorption was found in any of the six control
      animals. The authors' results point to the possibility that all features of
      prosthetic loosening that are ascribed to particle activation can be explained
      alternatively by effects of fluid pressure.

PMID- 9602822
TI  - Postirradiation aging affects stress and strain in polyethylene components.
AB  - Ultrahigh molecular weight polyethylene components oxidatively degrade because of
      gamma radiation sterilization and subsequent shelf aging in air. The effects of
      shelf aging on the stresses and strains associated with surface damage in tibial
      and acetabular components were examined. A material model was developed to
      predict the stress and strain relationship of oxidatively degraded polyethylene
      as a function of density using samples of polyethylene that were gamma radiation
      sterilized and evaluated immediately after irradiation and after 42 months of
      shelf aging. The finite element method was used to determine the stresses and
      strains before and after shelf aging for two tibial components with different
      conformities between the articulating surfaces and for an acetabular component.
      The stresses increased by 10% to 14% in the conforming tibial model after 42
      months of aging, whereas the stresses in the nonconforming tibial model and in
      the acetabular model increased by only 4% to 8%. Aging decreased the principal
      strains by 5% to 10% in both tibial models and by 15% to 17% in the acetabular
      model. Postirradiation aging during shelf storage of polyethylene joint
      components is likely to worsen long term wear, based on the increased stresses
      and decreased strains predicted to occur as a result of aging.

PMID- 9602823
TI  - Enhancement of bone formation in the setting of repeated tissue deformation.
AB  - The purpose of this study was to investigate whether the osteoinductive
      recombinant human bone morphogenetic protein 2, combined with a collagen carrier,
      could enhance bone formation when exposed to controlled amounts of tissue
      deformation. Chambers that allow for the multiple harvestings of tissue specimen
      were used. The devices were implanted in the tibial metaphyses of skeletally
      mature New Zealand White rabbits. A tissue ingrowth canal in each device either
      was left empty or filled with a collagen carrier with or without 0.6 microgram of
      recombinant human bone morphogenetic protein 2. The tissue ingrowth canal was
      deformed cyclically during a period of 2 minutes daily, according to a previously
      described deformation protocol. The tissue that developed in the chambers was
      harvested every 3 weeks. Undecalcified histologic sections of each tissue sample
      were stained with trichrome and von Kossa stains and subjected to
      histomorphometric analysis. It was found that deformation decreased the area
      occupied by bone trabeculae in the empty chambers and carrier controls. The
      amount of bone formed in the chambers treated with bone morphogenetic protein 2
      was significantly greater than that in the chambers subjected to micromotion and
      left empty or implanted with the collagen carrier. The amount of bone in chambers
      with motion and bone morphogenetic protein 2 was equal to that in chambers left
      empty and not subjected to micromotion. Qualitative histologic analysis of the
      bone formed with bone morphogenetic protein 2 revealed normal bone trabeculae.
      These findings indicate that bone morphogenetic protein 2 may be useful in
      augmenting bone formation in conditions that otherwise would favor the formation
      of fibrous tissue.

PMID- 9602824
TI  - Fatigue model to characterize cement-metal interface in dynamic shear.
AB  - This study evaluated the interface shear strength between vacuum mixed polymethyl
      methacrylate and two types of surface enhancements under static and dynamic shear
      loading. Cobalt chrome coupons with grit blasted or light plasma sprayed surfaces
      were tested. For each test, two coupons were mounted in a stainless steel chamber
      such that they were bonded with a 2-mm cement mantle for each test. Pullout and
      dynamic fatigue tests were performed on an Instron machine. The mean static
      pullout strength of the grit blasted surfaces was 13.78 (+/- 2.73) MPa, whereas
      that of the light plasma sprayed surfaces was 18.46 (+/- 1.98) MPa. The rate of
      degradation of interface strength caused by fatigue was almost identical for both
      surface treatments. Qualitative analysis showed that the failed light plasma
      sprayed surface generated more metal and cement particles. These data suggest
      that light plasma sprayed surfaces sustain higher loads but have a potential for
      increased debris generation.

PMID- 9602825
TI  - Biomechanical assessment of compression screws.
AB  - A series of mechanical tests on anatomic specimen cancellous bone and cancellous
      bonelike foam were conducted to evaluate and compare an Acutrak compression screw
      with an AO 4-mm cancellous screw and the Herbert screw. The Acutrak and AO screws
      produced similar fragment compression in foam and bone; Acutrak and AO
      compression were significantly greater than that of the Herbert screw. However,
      Acutrak was able to maintain compression after cyclic loading significantly
      better than were the AO and Herbert screws. The pushout force of Acutrak and AO
      screws were significantly greater than that of the Herbert screw in foam and
      bone. The torque required to break fragment contact was significantly greater for
      the Acutrak than for the AO or Herbert screws, but that for the AO was greater
      than that for the Herbert screw. The results of this analysis show the Acutrak
      screw is capable of producing and maintaining compression between bone fracture
      fragments. In addition, the Acutrak screw was shown to have superior mechanical
      characteristics than did Herbert screw in every mode tested. The Acutrak screw
      did not surpass the fragment compression achieved by the AO screw in foam, but it
      did not overtighten or experience degradation of compression after 500 cycles of
      simulated physiologic loading.

PMID- 9602826
TI  - Biochemical pathway mediating the response of bone cells to capacitive coupling.
AB  - Rat calvarial bone cells or mouse MC3T3-E1 bone cells subjected to a capacitively
      coupled electric field of 20 mV/cm consistently showed significant increases in
      cellular proliferation as determined by deoxyribonucleic acid content. Verapamil,
      a membrane calcium channel blocker; W-7, a calmodulin antagonist; indocin, a
      prostaglandin synthesis inhibitor; or bromophenacyl bromide, a phospholipase A2
      inhibitor, each at a concentration that did not interfere with cell proliferation
      in control cultures, inhibited proliferation in those cultures subjected to the
      electric field. In contrast, neomycin, an inhibitor of the inositol phosphate
      cascade, did not inhibit this electrically induced cellular proliferation.
      Prostaglandin E2 production also was increased significantly with electrical
      stimulation, and this increase was inhibited by verapamil or indocin but not by
      neomycin. Thus, the data suggest that the signal transduction mediating the
      proliferative response of cultured bone cells to a capacitively coupled field
      involved transmembrane calcium translocation via voltage gated calcium channels,
      activation of phospholipase A2, and a subsequent increase in prostaglandin E2.
      Increases in cytosolic calcium and activated calmodulin are implied. The inositol
      phosphate pathway, unlike its dominant role in signal transduction in
      mechanically stimulated bone cells, does not appear to play a role in signal
      transduction in the proliferative response of bone cells to electrical
      stimulation.

PMID- 9602827
TI  - Can specialists reduce costs? The case of referrals to orthopaedic surgeons.
AB  - This study investigates whether timely referral to specialists, in this case
      orthopaedic surgeons, potentially can reduce the costs of a health care episode.
      Five musculoskeletal diagnoses were chosen, and the diagnostic and treatment
      history of approximately 2500 persons with these five diagnoses was traced to
      determine when in the course of their treatment episode they were referred from
      nonorthopaedist to orthopaedist care and how much their episode of care cost. It
      was found that the average episodic costs for those who were referred earlier in
      the episode of care was lower than for those referred later. The implication is
      that there are likely to be numerous identifiable health conditions that should
      be flagged for early referral to specialists to reduce costs. It also questions
      the validity of the presumption that specialist care is necessarily more
      expensive.

PMID- 9602828
TI  - Inguinal swelling in a 5-year-old girl.

PMID- 9602829
TI  - A curriculum for the ideal orthopaedic residency.

PMID- 9602831
TI  - The role of neuroticism and mastery in spouse caregivers' assessment of and
      response to a contextual stressor.
AB  - Data from more than 300 spousal caregivers and their care recipients were
      analyzed to demonstrate the effects of caregivers' personality attributes-
      neuroticism and mastery--on their assessment of a contextual stressor (the care
      recipient's behavioral and functional impairment) and on their experience of
      distress associated with that stressor. Caregivers who were high in neuroticism
      and/or low in mastery reported higher levels of behavioral and functional
      impairment in their disabled spouse and experienced more strain and depressive
      symptoms associated with caregiving relative to caregivers with lower neuroticism
      or higher mastery scores. We further showed that the widely reported association
      between caregiver-assessed impairment of the care recipient and caregiver
      outcomes can in part be explained by caregivers' personality attributes, such as
      neuroticism and mastery. Our findings that caregivers' personality variables are
      related to their assessment of a given objective stressor and their response to a
      given level of stress have implications for interventions targeting caregivers
      and for the use of caregivers as proxy informants.

PMID- 9602830
TI  - Attachment style and emotion regulation in dementia patients and their relation
      to caregiver burden.
AB  - One hundred and sixty-eight patients with mid- to late-stage dementia and their
      caregivers participated in a study of the relation between patient emotional
      characteristics, dementia symptomatology, and caregiver burden. Measures included
      premorbid attachment style, premorbid emotion regulation style, and behavioral
      symptoms of dementia. The attachment patterns (secure, avoidant, ambivalent) of
      these elderly patients resembled those obtained in samples of younger individuals
      in terms of emotion regulation characteristics; however, the distribution of
      attachment styles was significantly different, with a lower proportion of
      ambivalently attached individuals in the present sample. In terms of the
      behavioral symptoms of dementia, ambivalent patients had more depression and
      anxiety than secure and avoidant patients; the latter patients experienced more
      activity disturbance than ambivalently attached individuals and were higher on
      paranoid symptomatology than securely attached persons. Caregivers of securely
      attached individuals experienced less total burden than did caregivers of both
      insecure groups. In regression analysis, attachment style accounted for the
      largest proportion of unique variance in the prediction of caregiver burden (8%);
      only 1 of 7 patient symptoms contributed a significant independent effect, namely
      depressed affect, which accounted for 4% of the variance.

PMID- 9602832
TI  - Associations among caregiving difficulties, burden, and rewards in caregivers to
      older post-rehabilitation patients.
AB  - The associations between self-reported rewards and difficulties of caregiving and
      burden were examined in a sample of 200 informal caregivers to older post
      rehabilitation patients. Sixteen percent (16%) of caregivers reported that
      caregiving was physically difficult only, 15% reported emotional difficulties
      only, 11% reported social difficulties only, 17% reported multiple difficulties,
      and 40% had no difficulties. Each type of difficulty (e.g., social, emotional,
      and physical) was significantly associated with burden in univariate and multiple
      linear regression analyses, controlling for confounding characteristics.
      Caregivers reporting multiple types of difficulty experienced higher levels of
      burden than caregivers who reported only one type of difficulty. Caregivers who
      received more rewards from caregiving reported fewer difficulties. Caregiving
      rewards had no independent effect on burden but modified the associations between
      social and emotional difficulties and burden. In summary, caregiving rewards and
      difficulties were not mutually exclusive, and their relationship in turn affected
      burden.

PMID- 9602833
TI  - Aging and impression formation: the impact of processing skills and goals.
AB  - Two studies assessed age differences in representations and judgments about
      people. Our specific interest was in examining how presumed age-related changes
      in processing efficiency and motivation affected performance in an impression
      formation task. Consistent with age-related declines in processing efficiency, we
      found that increasing age was associated with: (a) no change in the processing of
      evaluative information; (b) less use of specific traits to organize impressions;
      (c) poorer memory for behavioral information, especially when it contradicted
      expectations; and (d) less systematic relationships between memory and judgments.
      We also found, however, that more meaningful task goals and a focus on individual
      behaviors resulted in reduced age differences in the nature of representations
      about the target person.

PMID- 9602834
TI  - Visual search tasks: slowing of strategic and nonstrategic processes in the
      nonlexical domain.
AB  - Some investigators have argued that aging affects the slowing of processes in
      nonlexical tasks more than it does the slowing of processes in lexical tasks, but
      that within task domains, the slowing is identical. Other investigators have
      argued that even within nonlexical tasks there is differential slowing such that
      aging affects processing speed more in (nonlexical) coordinative tasks than it
      does in (nonlexical) sequential tasks. Perhaps, more finely still, there is a
      differential slowing in coordinative nonlexical tasks. Toward this end, latent
      models of general and process-specific slowing in coordinative nonlexical tasks
      were formulated for older adults. A visual search task was then used to test the
      two types of models. It was found that a latent model of process-specific slowing
      explained significantly more of the variability than a latent model of general
      slowing, indicating that there is a differential slowing of processes among
      coordinative tasks within the nonlexical domain. It was also discovered that the
      coordinative process most greatly affected was that of deciding to terminate the
      search when no target was present in the display, indicating together with other
      studies a possible difference in the slowing of strategic processes among both
      coordinative and sequential tasks within the nonlexical domain, but no difference
      in the slowing of nonstrategic processes.

PMID- 9602835
TI  - Black/white differences in the relationship between MMSE scores and disability:
      the Women's Health and Aging Study.
AB  - The purpose of this article is to examine Black/White differences among older
      women in the relationship between physical functional difficulties and variations
      in cognitive status, measured within the low to high normal range of the Mini
      Mental State Examination (MMSE). We studied 3,585 women with MMSE scores of 18
      and above from a population-based random sample of 3,841 community-dwelling women
      aged 65 and older living in East Baltimore, Maryland. Trained interviewers
      administered the MMSE and obtained information on demographics, medical
      conditions, and functional difficulties. Prevalence of any functional difficulty
      was 43.3% in Whites and 48.5% in Blacks, who were 25% of the study sample. After
      adjusting for age and education, a significant trend for increasing functional
      difficulty with decreasing MMSE scores was found in White women but not in Black
      women. Since no explanation for these racial differences could be identified,
      these findings suggest that the MMSE may not be a valid predictor of functional
      difficulty in Black women who score > or = 18 on the instrument.

PMID- 9602836
TI  - Religiosity buffers effects of some stressors on depression but exacerbates
      others.
AB  - Although religiosity is protective for mortality and morbidity, its relationship
      with depression is unclear. We used the 1994 Alameda County Study survey of 2,537
      subjects aged 50-102 to analyze associations between two forms of religiosity and
      depression as well as the extent to which religiosity buffers relationships
      between stressors and depression. Non-organizational religiosity included prayer
      and importance of religious and spiritual beliefs; organizational religiosity
      included attendance at services and other activities. Non-organizational
      religiosity had no association with depression; organizational religiosity had a
      negative relationship that weakened slightly with the addition of health
      controls. Both forms of religiosity buffered associations with depression for non
      family stressors, such as financial and health problems. However, non
      organizational religiosity exacerbated associations with depression for child
      problems, and organizational religiosity exacerbated associations with depression
      for marital problems, abuse, and caregiving. Religiosity may help those
      experiencing non-family stressors, but may worsen matters for those facing family
      crises.

PMID- 9602837
TI  - Are expectations for care related to the receipt of care? An analysis of parent
      care among disabled elders.
AB  - This investigation explores the relationship between the degree to which older
      parents expect assistance from their children and the actual amount of care they
      receive from their children. Combining the theories of reasoned action and
      intergenerational solidarity, we hypothesize that global expectations (social
      norms about receiving care) influence specific expectations (behavioral
      intentions to seek care), but that it is specific expectations that influence the
      amount of care received from children. Data were collected at three points over a
      12-month period among a sample of impaired older parents (65+) who lived
      independently in community settings (n = 334). Using structural equation models,
      the results were consistent with the hypothesis. We conclude that the theory of
      reasoned action is a useful adjunct to the theory of intergenerational solidarity
      by proposing that parents adjust their global expectations to reflect the
      specific realities of the lives of their children.

PMID- 9602838
TI  - Spouse-rated limitations and spouse-rated life expectancy as mortality
      predictors.
AB  - Survival analyses are used to examine the predictive value of spouse-rated
      limitations due to health problems and spouse-rated life expectancy for 3-year
      mortality in a communication sample of elderly Australian married couples, net of
      health status indicators, health behaviors, and sociodemographic factors. Tests
      for gender differences in the effects and for empirical overlap with self-ratings
      of health expectancy were also done. Findings show that both spouse-ratings are
      predictive of husbands' mortality, while for wives' mortality the parallel
      measures are not predictive in the adjusted model. Wives' rating are not
      substitutes for other health indicators or for self-ratings of health and life
      expectancy. The independent effect suggests that wives are more astute reporters
      or judges of their husbands' mortality risk for that wives' perceptions indicate
      tangible influences on husbands' health and mortality risk. Future analyses
      should be directed toward finding mechanisms linking spouse perceptions to health
      outcomes.

PMID- 9602839
TI  - Is self-rated health comparable across cultures and genders?
AB  - Self-rated health is a frequently used health indicator, but there is little data
      on its comparability across cultures. We employed samples from Tampere, Finland,
      and Florence, Italy, of the European Longitudinal Study on Aging to examine the
      cultural and gender differences in self-rated health. Personal interview data was
      used and vital status ascertained after 7 years. After adjusting for several
      health-related variables, we found no substantial difference in self-rated health
      between genders, although women in Florence were three times and men in Florence
      four times more likely to report good self-rated health than men in Tampere. The
      correlational structure of self-rated health was similar in both areas. The
      significant graded association between self-rated health and mortality in both
      areas was mostly explained by other health indicators included in a multivariate
      model. Results suggest that self-rated health is a useful summary of physical
      health, but it may predict mortality better in men than in women and be sensitive
      to cultural environment. Therefore, direct gender and cultural comparisons of
      self-rated health should be made with caution.

PMID- 9602840
TI  - Older parents' expectations of moving closer to their children.
AB  - Research shows that older parents engage in return migration in older to live
      closer to children from whom they receive care. However, less is known about how
      characteristics of adult children influence this process. Data for this analysis
      are from 5,382 older parents participating in the 1993/4 AHEAD national survey of
      adults aged 70 years old and older. Findings demonstrate that elderly parents who
      expect to move closer to adult children tend to be older, female, and have at
      least one child who is better-off financially than they are. Living alone
      magnifies the effect of poor self-rated health on expecting to move closer to a
      child. Random effects modeling of children's characteristics reveals that parents
      are more likely to expect to move closer to a daughter than to a son. Greater
      parental functional impairment was found to further depress the selection of
      sons. Overall, the findings suggest that older parents expect to move closer to
      adult children out of need and tend to select a target child with greater
      potential to provide support.

PMID- 9602841
TI  - Custodial grandparenting and the impact of grandchildren with problems on role
      satisfaction and role meaning.
AB  - This study compared three groups of grandparents, attempting to disentangle
      grandparental role demands from child-specific problems as sources of role
      specific and grandchild-relationship distress. Those grandparents raising
      grandchildren reported to demonstrate neurological, physical, emotional, or
      behavioral problems exhibited the most personal distress, the least role
      satisfaction and role meaning, and the most deteriorated grandparent-grandchild
      relationships. Custodial grandparents raising grandchildren reported to have few
      difficulties also differed in the ways listed above from those grandparents not
      raising their grandchildren and from those raising grandchildren displaying
      problems. For men, but not women, more positive grandparent meaning was
      associated with raising a grandchild. Significantly, custodial grandparents were
      more likely to be raising boys, suggesting that boys may be either more difficult
      for grandparents to raise or that boys react more negatively to the adverse
      circumstances under which grandparents assume care.

PMID- 9602842
TI  - The history of ultrasound.
AB  - Diagnostic medical ultrasound may have a brief history, but its roots date back
      to the early nineteenth century. From its modest beginnings in military
      institutions where ultrasound was used to examine pathologic specimens, to the
      routine evaluation of the fetus, injured patients, and those with cerebrovascular
      disease, ultrasound has secured a position as a key diagnostic test both
      currently and in the future. Its ability to diagnose valvular and congenital
      heart disease has reduced the need for invasive cardiac angiography with its
      attendant risks. Furthermore, endoluminal, transvaginal, transrectal, and
      transesophageal ultrasound have expanded physicians' diagnostic armamentarium and
      ability to "look inside" their patients. Notwithstanding all these advancements,
      ultrasound research and development continue to be fostered, and the ideas of
      today will be the technology of tomorrow (Fig. 5).

PMID- 9602843
TI  - Ultrasound physics and instrumentation.
AB  - A knowledge of the principles of ultrasound physics and instrumentation allows
      the surgeon to maintain proper ultrasound techniques and obtain the best possible
      image. Furthermore, when these principles are understood, artifacts and pitfalls
      of imaging are avoided.

PMID- 9602844
TI  - Breast ultrasound.
AB  - Ultrasound of the breast has been demonstrated to be an extremely effective tool
      in the evaluation of mammographically detected breast lesions. The technique is
      relatively straightforward and may be learned in a relatively short time by
      experienced breast clinicians. It is likely that the future care of patients with
      diseases of the breast will continue to be increasingly dependent on image-guided
      breast biopsy techniques. Therefore, surgeons would do well to familiarize
      themselves with this modality. This is likely to streamline patient care, improve
      cost efficiency, and facilitate therapeutic planning. Finally, the current health
      care climate is likely to encourage the use of ultrasound of the breast by
      surgeons.

PMID- 9602845
TI  - Endorectal ultrasound.
AB  - Endorectal ultrasound is a very useful diagnostic adjunct for benign and
      malignant anorectal diseases. The only prerequisite in performing this test is
      that the examiner appreciate the impact that EUS has on the clinical management
      of patients. For example, the information obtained when scanning rectal cancer
      dictates whether local excision (i.e., sphincter preservation) or preoperative
      adjuvant therapy followed by radical resection is chosen. For benign disease, EUS
      helps direct therapy for patients with fecal incontinence and selects those
      patients most likely to benefit from reconstructive surgery.

PMID- 9602846
TI  - Intraoperative and laparoscopic ultrasound.
AB  - Intraoperative ultrasound, whether during celiotomy or laparoscopy, plays an
      important role in assisting the surgeon in directing appropriate therapy for
      intra-abdominal diseases, particularly primary or metastatic malignancies
      involving the liver and primary malignancies of the pancreas and upper
      gastrointestinal tract. It is the most sensitive imaging technique for detecting
      small intraparenchymal lesions of the liver, pancreas, and other solid organs.
      Owing to its increased sensitivity over all commonly used preoperative imaging
      studies, it is responsible for changing the intraoperative treatment plan of
      these tumors in a significant percentage of cases. This is particularly true with
      respect to resectability. In the era of laparoscopic surgery, it replaces the
      surgeon's inability to palpate the liver and other organs during surgery. As
      surgeons use a laparoscopic approach with increasing frequency to treat intra
      abdominal disease, they will have an increasing need to master the use of
      intraoperative ultrasound in order to render optimal care to their patients.

PMID- 9602847
TI  - Vascular ultrasound.
AB  - Surgeon-interpreted diagnostic ultrasound has become the preferred screening test
      and often the definitive test for the diagnosis of arterial stenosis, aneurysm,
      and venous thrombosis. As a modality for surveillance, its noninvasive quality
      makes it particularly appealing as the test of choice to screen patients for
      abdominal aortic aneurysms or to perform follow-up examinations on those patients
      with a carotid endartectomy or in situ bypass grafts. The increasing reliance on
      intraoperative duplex imaging of vascular procedures demands that the surgeon
      learn the skills to perform the studies without a technologist or radiologist to
      interpret the examination.

PMID- 9602848
TI  - Ultrasound as used in thoracoabdominal trauma.
AB  - Because it is unique in being portable, rapid, and noninvasive, ultrasound is
      particularly suited to the trauma setting. When performed by the surgeon, it
      offers immediate feedback that can be incorporated into the management plan for
      the patient. Multiple studies in this area have now documented that surgeons can
      perform and interpret focused ultrasound examinations. Enthusiasm for surgeons as
      ultrasonographers will likely increase now that the Advanced Trauma Life Support
      Subcommittee of the American College of Surgeons has published an algorithm that
      includes ultrasound for the assessment of patients with blunt truncal injuries.
      As a rapid, sensitive, and specific diagnostic test for the detection of
      pericardial tamponade, hemothorax, and hemoperitoneum, ultrasound is now an
      integral part of the practice at many Level I trauma centers.

PMID- 9602849
TI  - The surgeon's use of transesophageal echocardiography.
AB  - Transesophageal echocardiography has become an instrumental diagnostic modality
      for the accurate evaluation of cardiac and aortic anatomy and function.
      Multiplanar technology has facilitated improved visualization of structures and
      enhanced TEE over TTE in many situations. Care of the trauma patient and
      critically ill patient is improved with the appropriate and timely performance of
      TEE. Education, certification, credentialing, and determination of competency are
      areas that need to be addressed continually in the future.

PMID- 9602850
TI  - The surgeon's use of ultrasound in the acute setting.
AB  - As the role of the general surgeon continues to evolve, the surgeon's use of
      ultrasound will surely influence practice patterns, particularly for the
      evaluation of patients in the acute setting. With the use of real-time imaging,
      the surgeon receives "instantaneous" information to augment the physical
      examination, narrow the differential diagnosis, or initiate an intervention. With
      select ultrasound examinations, the surgeon can rapidly evaluate adult and
      pediatric patients who present with an acute abdomen, especially those in shock.
      In the hands of the surgeon, this noninvasive bedside tool can more accurately
      assess the presence, depth, and extent of an abscess, confirm complete
      aspiration, or diagnose wound dehiscence before it is apparent on physical
      examination. Ultrasound is so accurate for the diagnosis of pyloric stenosis that
      it has essentially replaced the upper gastrointestinal series in most
      institutions. The surgeon's use of ultrasound to detect a pleural effusion has
      virtually replaced the lateral decubitus film. Furthermore, an ultrasound-guided
      thoracentesis not only facilitates the procedure but improves its safety. Many
      ICUs now have protocols in place to perform routine duplex surveillance of those
      patients who are considered at high risk for the development of thromboembolic
      complications. As surgeons become more facile with ultrasound, it is anticipated
      that other uses will develop to further enhance its value for the assessment of
      patients in the acute setting.

PMID- 9602851
TI  - Evidence-based screening: what kind of evidence is needed?

PMID- 9602852
TI  - Increased frequency of micronucleated kidney cells in rats exposed to halogenated
      anaesthetics.
AB  - Six halogenated anaesthetics were tested for their ability to induce micronuclei
      formation in the rat kidney. A statistically significant increase in the
      frequency of micronucleated cells was detected in rats given a single p.o. dose
      of 4 mmol/kg of halothane (3.48 x baseline), chloroform (3.32 x baseline),
      trichloroethylene (3.24 x baseline), sevoflurane (2.98 x baseline), and
      isoflurane (2.95 x baseline). In contrast, the response was substantially
      negative in rats given the same dose of enflurane. As compared to controls, rats
      treated with halothane and trichloroethylene displayed a reduction in the
      frequency of binucleated cells presumably due to a toxicity-induced inhibition of
      cellular proliferation. These findings suggest a potential genotoxic activity of
      halogenated anaesthetics for the rat kidney.

PMID- 9602853
TI  - Transient hypothermia induces micronuclei in mice.
AB  - We investigated the effect of hypothermia on micronucleus induction in mouse bone
      marrow cells. To induce hypothermia, we administered chlorpromazine, which was
      negative in an in vitro chromosome aberration test, at 3.13, 6.25, 12.5, 25, 50,
      and 100 mg/kg intraperitoneally. Doses of 12.5-100 mg/kg decreased rectal
      temperature transiently to less than 33 degrees C. The temperature depression
      following 25-100 mg/kg lasted for 11 h before returning to normal 24 h later
      except for the 100 mg/kg treatment group. Doses of 25-100 mg/kg produced a
      statistically significant (p < 0.01) increase in micronucleated polychromatic
      erythrocyte frequencies 48 h after dosing. When mice that were administered
      chlorpromazine at 25, 50, and 100 mg/kg were exposed to an environmental
      temperature of 30 degrees C for 46 h to keep their body temperature within normal
      range, the frequency of micronucleated erythrocytes did not increase. In
      addition, relatively large micronuclei (diameter of micronucleus > or = 1/4
      diameter of cytoplasm) accounted for 53-58% of the induced micronuclei. The
      results suggest that the transient hypothermia of less than 33 degrees C for 11 h
      induced micronuclei in bone marrow cells, and one possible mechanism was
      disturbance of the mitotic apparatus.

PMID- 9602854
TI  - Evaluation of the genotoxicity of aniline.HCl in Drosophila melanogaster.
AB  - The induction of X-chromosome malsegregation, sex-linked recessive lethals and II
      III autosomal translocations by aniline.HCl was investigated in Drosophila
      melanogaster. Nondisjunction was tested in 2 and 4 d old virgin females fed on
      aniline.HCl solutions (3, 5, 10 and 15%) using a system where exceptional females
      (XXY) and only 1/4 of the expected regular progeny are viable. After mating, the
      females were subcultured daily. Similarly treated 7-day-old wild-type males were
      used to run classical II-III translocation and recessive lethal tests; for the
      latter, the solutions were also injected intraabdominally. In all cases, five
      broods were obtained. A direct correlation was observed between concentration and
      toxicity. Furthermore, males were more sensitive than females, and the latter's
      sensitivity was higher at 4-day-old than at 2-day-old. This could be attributed
      to a decrease with age in the efficiency of a detoxifying mechanism, or to the
      generation of a toxic metabolite in older flies. Significant increases in
      nondisjunction were observed with 5, 10 and 15% solutions suggesting the
      existence of a threshold. No dose effect was detected within the range of the
      effective concentrations used. The increases were observed in the first
      subculture (representing mostly stage 14 oocyte, i.e., cells in metaphase I) and
      in the third subculture, representing cells in which the spindle has not yet
      formed, thereby pointing to a direct effect of the chemical on the chromosomes
      and not on the spindle. It is proposed that the second sensitivity peak detected
      might be the outcome of the transient loss of a protective configuration provided
      by the karyosome, due to its expansion in stages 9 and 10 of the developing
      oocytes. No sex-linked lethals or translocations were induced.

PMID- 9602855
TI  - In vivo response of mouse liver to gamma-radiation assessed by the comet assay.
AB  - The alkaline comet assay was used to measure DNA damage induced in liver cells of
      mice irradiated with gamma-radiation, as well as the repair competency of these
      cells. A simplified procedure for the isolation of nuclei from cells in solid
      tissues was developed. This simplified method allows nuclei to be processed into
      lysis only 5 min after briefly chilling the tissue to depress any enzymatic
      activity. The nuclei were spontaneously released by a sharp cut of the tissue and
      exposure of the cut to a drop of 50 mM sodium-phosphate buffer at pH 7.2,
      immediately before adding the low melting agarose. Thus, the procedure minimizes
      time-dependent modification of the endogenous level of damage by reducing
      additional strand breaks or repair produced during processing. The induction of
      DNA damage by gamma-radiation behaved as a one-hit event in the liver cells, as
      there was a positive linear correlation between the radiation dose and the
      fraction of DNA migrated into the comet tails. The level of DNA damage produced
      by gamma-radiation was highly significant at doses of 0.5 and 1 Gy. Based on the
      mean extent of DNA migration, the level of damage was not reduced following only
      one hour of repair time however, after two hours, there was a significant
      reduction in DNA migration. To increase the resolution of the statistical
      analysis, the nuclei of each sample were distributed in five types of comets,
      according to the percentage of DNA in the tail. To compare the frequency
      distributions of these types of comets between different experimental situations,
      a Pearson chi-square statistical analysis was applied. It was found, by this
      analysis, that the DNA repair which occurred 1 h after 1 Gy of gamma-irradiation
      is significant and that, after 2 h, more DNA repair occurs, but a significant
      residual damage still persists when comparing this sample with the control.

PMID- 9602856
TI  - Aneuploidy induced by dimethylarsinic acid in mouse bone marrow cells.
AB  - We investigated the cytogenetic effects of dimethylarsinic acid (DMA), which is
      the major metabolite of inorganic arsenic compounds, on mouse bone marrow cells
      after a single intraperitoneal injection to mice. DMA increased mitotic indices
      significantly at 16, 24 and 48 h after injection, and prolonged the average
      generation time 1.5 h at the 24 h. These results suggest that DMA may cause
      mitotic arrest in vivo as well as in vitro. However the activity of mitotic
      arrest induced by DMA was much weaker than that induced by colchicine. Metaphase
      cells obtained after administration of DMA without colchicine pretreatment were
      morphologically normal except for chromosome number, which varied by stage from
      the prophase to the telophase in M phase as seen after administration of saline.
      DMA significantly induced aneuploids. The frequencies of euploids with DMA and
      saline treatment were 55.1 and 94.0%, respectively, and in DMA treatment
      hyperploids with 1 or 2 extra chromosomes were over 80% of all aneuploids. These
      results suggest that aneuploidy induced by DMA might be associated with
      carcinogenicity of arsenic.

PMID- 9602857
TI  - Differential effects of aneugens and clastogens on incidences of multinucleated
      cells and of micronucleate cells in Chinese hamster lung (V79) cell line in
      vitro.
AB  - Two aneugens, vinblastine (0.025-0.4 microgram/ml) and colchicine (0.05-0.4
      microgram/ml), and two clastogens, mitomycin C (0.05-0.4 microgram/ml) and
      cyclophosphamide (1-16 micrograms/ml) were applied respectively to the
      micronucleus test in Chinese hamster lung (V79) cells in vitro, and the frequency
      of multinucleated cells (Fmu) and that of micronucleate cells (Fmi) in each group
      were observed. The results showed that at relatively high concentrations, all
      four agents increased both Fmu and Fmi, but the ratios of Fmu to Fmi in groups of
      the two aneugens (average of 2.2, 2.8, respectively) were much (10-30 folds)
      higher than that in groups of the two clastogens (0.09, 0.20). The difference
      between aneugens and clastogens in the above ratio was much more remarkable than
      that in areas of micronuclei (only 1.6-2.5 folds for the latter). At relatively
      low concentrations, the two clastogens increased only Fmi (but not Fmu), while
      the two aneugens increased only Fmu (but not Fmi). This indicates that the
      induction of multinuclei by aneugens may be more sensitive than by clastogens,
      and the induction of micronuclei by clastogens may be more sensitive than by
      aneugens. So, it is possible for the ratio of Fmu to Fmi to become a simple and
      sensitive (though indirect) index for distinguishing aneugens from clastogens.
      Further studies with other mutagens and (or) other cell types will be needed to
      confirm the deduction. As no difference in frequency of polyploid cells was
      observed between control group and each treatment, the multinucleation does not
      seem related to endoreduplication of chromosomes.

PMID- 9602858
TI  - Is micronuclei yield variability a problem for overexposure dose assessment to
      ionizing radiation?
AB  - Scoring of micronuclei (Mni) in cytokinesis-blocked human blood peripheral
      lymphocytes after an accidental radiation overexposure appears an easier and
      faster alternative for biological dosimetry than dicentrics analysis. However, an
      increase of Mni rate could be difficult to interpret particularly at low doses,
      because of the known variability of individual dose response and the unknown
      background frequency. Moreover, in case of nuclear emergency, there are the added
      problems of large samples numbers for processing and so screening time. In this
      paper, we wish to propose some solutions using both methodological and
      statistical approaches. Firstly, we have tried to check the micronuclei assay in
      order to obtain a sufficient number of micronuclei in binucleated cells in the
      shortest time possible, even at higher exposition dose. Two techniques were
      compared using frequencies of binucleated cells and micronuclei in normal
      lymphocytes and after exposure to gamma-irradiation (60 Co) for doses up to 6 Gy.
      Secondly, we have supposed that, if the individual radiosensitivity was a
      critical problem for dose estimation, conversely, it would be not possible to
      build a reference curve combining many individuals. Thus, we have assessed the
      Mni response from 47 carefully selected healthy male blood donors for gamma
      irradiation between 0 and 4 Gy. We show in this study that a realistic dose
      effect relationship could be always fitted. In addition, the related coefficients
      could be compared with other published dose-effect relationships for gamma rays.
      However, the background incidence calculated from these 47 healthy individuals
      were found to be larger as expected so that this approach increases the detection
      limit for which an overexposure suspicion could be significantly detected to 0.32
      Gy.

PMID- 9602859
TI  - Automatic analysis of the in vitro micronucleus test on V79 cells.
AB  - The in vitro micronucleus test is a well established test for early screening of
      new chemical entities in industrial toxicology. For assessing the clastogenic or
      aneugenic potential of a test compound, micronucleus induction in cells has been
      shown repeatedly to be a sensitive and specific parameter. As a measure for
      numerical and structural chromosome aberrations, the in vitro micronucleus test
      consists of determining the frequency of micronucleated cells in a representative
      fraction of cells in a culture. So far, manual counting has been the only method
      for evaluating microscopic V79 Chinese hamster cell preparations. To replace this
      tedious and time consuming procedure, a fully automatic system for micronucleus
      scoring in V79 cells by image analysis has been developed and introduced into the
      routine genotoxicity screening of drug candidates. The comparison of manual and
      automatic micronucleus analysis showed a high degree of concordance between the
      results obtained by the two techniques. For concentration series of
      cyclophosphamide (CP) and ethyl-methanesulphonate (EMS) as test compounds, the
      frequency of erroneously missed micronuclei through automatic scoring proved to
      be below 15% in comparison with manual scoring. Generally, false positive
      micronucleus decisions could be controlled easily by fast and simple relocation
      of the automatically detected patterns. The possibility to analyze 24 slides
      within 1 day by fully automatic overnight analysis and the high reproducibility
      of the results make automatic image processing a powerful tool for the in vitro
      micronucleus analysis.

PMID- 9602860
TI  - Sulfotransferase-mediated genotoxicity of propane 2-nitronate in cultured ovine
      seminal vesicle cells.
AB  - 2-Nitropropane (2-NP) is a well-known genotoxin and carcinogen in rat liver.
      Several metabolic pathways, particularly cytochrome P450-, peroxidase- and
      sulfotransferase-dependent ones, have been suggested to lead to the formation of
      DNA-reactive species from 2-NP. Because rat liver cells express most types of
      xenobiotic-metabolizing enzymes, the role of specific pathways in the metabolic
      activation of 2-NP is difficult to assess in these cells. We have therefore
      investigated the genotoxicity of 2-NP and its anionic form, propane 2-nitronate
      (P2N), in cultured ovine seminal vesicle (OSV) cells. OSV cells lack cytochrome
      P450-dependent monooxygenase activity, but express prostaglandin-H-synthase (PHS)
      and, as we found out, phenol sulfotransferase. The induction of DNA repair
      synthesis and specific DNA modifications served as indicators for the
      genotoxicity of 2-NP and P2N. Both forms strongly induced repair, P2N being more
      active than 2-NP. The secondary nitroalkanes nitrocyclopentane and
      nitrocyclohexane also induced repair, whereas 1-nitropropane and the reduction
      product of 2-NP, acetone oxime, did not. P2N also elicited the formation of the
      characteristic DNA modifications 'DX1' and 8-aminodeoxyguanosine and increased
      the level of 8-oxodeoxyguanosine residues in the DNA. Pretreatment of OSV cells
      with indomethacin, an inhibitor of PHS, affected neither the induction of repair
      nor the formation of the DNA modifications, and P2N was not a reducing substrate
      for the PHS-peroxidase activity. In contrast, the sulfotransferase inhibitor
      pentachlorophenol strongly reduced genotoxicity. The results show that cytochrome
      P450-dependent monooxygenases are not required for the metabolic conversion of
      secondary nitroalkanes or their nitronates into DNA-damaging products, nor is PHS
      involved in the metabolic activation. Instead, the data corroborate an essential
      role of sulfotransferase(s) in the genotoxicity and carcinogenicity of secondary
      nitroalkanes. Moreover, it is demonstrated for the first time that these
      compounds can be genotoxic in cells other than hepatocytes or hepatoma cells.
      This implies that in species other than the rat, organs other than the liver can
      be targets for the genotoxicity, and possibly carcinogenicity, of secondary
      nitroalkanes.

PMID- 9602861
TI  - Discrimination between genotoxicity and cytotoxicity in the induction of DNA
      double-strand breaks in cells treated with etoposide, melphalan, cisplatin,
      potassium cyanide, Triton X-100, and gamma-irradiation.
AB  - The dose-response relationships for DNA fragmentation (assessed by pulsed-field
      gel electrophoresis, PFGE) and for viability (evaluated by measuring the
      reduction of MTT dye which can be accomplished by viable cells only) were
      investigated in order to discriminate between genotoxicity and cytotoxicity in
      the pathogenesis of DNA double-strand breaks (DSB). Cultured human lung
      epithelial cells (A549) were treated with the DNA-intrastrand crosslinker
      cisplatin, the DNA-interstrand crosslinker melphalan and the topoisomerase II
      inhibitor etoposide. The cytotoxic mode of DSB induction was investigated by
      using the mitochondrial respiratory chain toxin potassium cyanide (KCN) and the
      detergent Triton X-100. gamma-Irradiation induced a linear dose response for DSB
      which were efficiently repaired and did not cause reduction in cell survival over
      a period of 72 h. With etoposide and melphalan a significant increase in DSB was
      seen 8 h after treatment initiation with concentrations that did not affect cell
      survival, implicating genotoxicity as the causal event. In contrast, induction of
      DSB by KCN and Triton X-100, and also by cisplatin, was seen only after cell
      viability was reduced to less than about 60%, indicating that DSB were the
      consequence of extragenomic damage. This mechanistic distinction of the two
      classes was supported by DNA fragment length analysis. In line with a genotoxic
      mechanism and absence of additional cytotoxic effects, the DNA fragments
      generated by gamma-irradiation as well as by etoposide and melphalan displayed a
      distribution between 1 and 4 Mbp with a peak around 2 Mbp. In contrast, DNA
      fragments induced by Triton X-100 and KCN peaked below 0.5 Mbp, implicating
      activation of DNA-degrading enzymes. This type of investigation is suggested for
      the study of chemicals for potential DNA interstrand crosslinking, an important
      promutagenic type of DNA damage. To avoid false positive results in genetic
      toxicity testing it is suggested that all assays include a dose-response
      relationship for both genotoxicity and viability.

PMID- 9602862
TI  - Topical application of alpha-tocopherol modulates the antioxidant network and
      diminishes ultraviolet-induced oxidative damage in murine skin.
AB  - The aim of this study was to investigate the effects of topical alpha-tocopherol
      application on epidermal and dermal antioxidants and its ability to prevent
      ultraviolet (UV)-induced oxidative damage. Hairless mice received topical
      applications of alpha-tocopherol 24 h before a single, acute UV irradiation (10 x
      minimal erythemal dose). The four major antioxidant enzymes (catalase, superoxide
      dismutase, glutathione reductase and glutathione peroxidase), hydrophilic and
      lipophilic antioxidants, and lipid hydroperoxides, markers of oxidative damage,
      were assayed in both epidermis and dermis of hairless mice. Topical alpha
      tocopherol treatment increased dermal superoxide dismutase activity by 30% (P <
      0.01) and protected epidermal glutathione peroxidase and superoxide dismutase
      from depletion after UV irradiation. Total and reduced glutathione levels in the
      epidermis increased by 50% after the topical treatment (P < 0.05), as did dermal
      ascorbate levels (by 40%: P < 0.01). The topical treatment increased alpha
      tocopherol levels both in the epidermis (62-fold) and the dermis (22-fold: P <
      0.001 in each layer). Furthermore, alpha-tocopherol treatment significantly
      reduced the formation of epidermal lipid hydroperoxides after UV irradiation (P <
      0.05). These results demonstrate that topical administration of alpha-tocopherol
      protects cutaneous tissues against oxidative damage induced by UV irradiation in
      vivo, and suggest that the underlying mechanism of this effect involves the up
      regulation of a network of enzymatic and non-enzymatic antioxidants.

PMID- 9602864
TI  - Tumour necrosis factor-alpha is involved in the contrasting effects of
      ultraviolet B and ultraviolet A1 radiation on the release by normal human
      keratinocytes of vascular permeability factor.
AB  - Erythema and the initiation of an inflammatory response are typical features of
      human skin after ultraviolet (UV) radiation (UVR) exposure. Among the soluble
      factors that account for the induction of an erythema, the most recently
      discovered is vascular permeability factor/vascular endothelial growth factor
      (VPF/VEGF), a potent inducer of microvascular permeability which is expressed by
      keratinocytes. As epidermal cells are the first target cells of UVR, we studied
      the effects of UVBR (312 nm) and UVA1R (365 nm) on the secretion of VEGF by
      normal human keratinocytes and evaluated the role of interleukin 1 alpha (IL-1
      alpha) and tumour necrosis factor-alpha (TNF-alpha) in this process. UVBR (100
      and 200 mJ/cm2) induced a dose-dependent increase in the release by normal human
      keratinocytes of VEGF, which is widely mediated through the release of TNF-alpha
      but not IL-1 alpha. Conversely, UVA1R (5 and 7 J/cm2) did not modify the basal
      level of VEGF and did not induce the secretion of TNF-alpha by keratinocytes.
      Moreover UVA1R, when associated with UVBR, inhibited the increase in VEGF induced
      by UVBR alone. Taken together, these findings indicate that UVBR and UVA1R have a
      contrasting effect on the release of VEGF, which is widely mediated by TNF-alpha.
      They may partly explain the minor erythematous effect of UVA1R and its beneficial
      role in cutaneous phototherapy.

PMID- 9602863
TI  - Contrasting effects of ultraviolet A1 and ultraviolet B exposure on the induction
      of tumour necrosis factor-alpha in human skin.
AB  - Ultraviolet B (UVB) irradiation of the skin causes immunosuppression which is
      relevant to the induction of skin cancer. The mechanism of this immunomodulation
      is unclear but various regulatory molecules have been implicated, including cis
      urocanic acid (cis-UCA) and the cytokines tumour necrosis factor-alpha (TNF
      alpha) and interleukin 10 (IL-10). Whether ultraviolet A (UVA) induces similar
      changes has not been investigated fully. We studied the effect of in vivo UVB and
      long-wave UVA (UVA1) exposure on the induction of TNF-alpha, IL-10 and cis-UCA in
      human skin. Volunteers were irradiated with three minimal erythema doses (MED) of
      UVB or UVA1. At different times after irradiation, suction blisters were raised
      from irradiated and from non-irradiated (control) skin. The TNF-alpha and IL-10
      protein concentration, and the percentage of cis-UCA in the blister fluid, were
      then determined. UVB irradiation of human skin led to a rapid and significant
      increase in TNF-alpha concentration in suction-blister fluid, with maximal values
      6 h after irradiation (n = 6, P < 0.05). In contrast, UVA1 irradiation led to a
      decrease in TNF-alpha concentration in the suction-blister fluid compared with
      non-irradiated skin, with the lowest values 6 h after irradiation (n = 6, P <
      0.05). Both UVB and UVA1 exposure of the skin induced a slight increase in IL-10
      concentration. However, the increase in IL-10 was only significant after UVB
      irradiation (UVB, n = 6, P < 0.05; UVA, n = 7, P < 0.1). As previously shown,
      both UVB and UVA1 result in the photo-isomerization of trans-UCA and an increased
      percentage of cis-UCA was found in the suction-blister fluid. Thus the results
      show differential effects of UVB and UVA1 irradiation on the induction of
      immunoregulatory molecules, which may help to explain the variation in immune
      responses after UVB and UVA1 exposure of human skin.

PMID- 9602865
TI  - The vitamin D3 receptor and retinoid X receptors in psoriatic skin: the receptor
      levels correlate with the receptor binding to DNA.
AB  - It is unknown whether vitamin D3 analogues improve psoriasis by overcoming an
      intrinsic abnormality of the vitamin D3 signalling pathway in psoriatic skin. The
      effects of vitamin D3 are mediated through the vitamin D3 receptor (VDR). The VDR
      heterodimerizes with another transcriptional regulator, preferentially the
      retinoid X receptor (RXR). In the present study the levels of VDR and RXR in
      involved and uninvolved psoriatic skin were determined by immunoblotting, and the
      binding of the VDR-RXR complex to a vitamin D3 response element (VDRE) consisting
      of two hexanucleotides spaced by three nucleotides (DR-3) by the electrophoretic
      mobility shift assay. The levels of VDR were similar in involved and uninvolved
      skin. RXR alpha, but neither RXR beta nor RXR gamma, was detectable. The RXR
      alpha levels were slightly lower in involved psoriatic skin than in uninvolved
      psoriatic skin, but this difference was statistically insignificant. The binding
      of VDR-RXR to the DR-3 VDRE was similar in uninvolved and involved psoriatic
      skin. Furthermore, there was a strong linear correlation between the levels of
      both VDR and RXR alpha and their binding to DNA. In conclusion, the initial part
      of the vitamin D3 signalling pathway involving receptor levels and receptor
      binding to DNA is normal in involved psoriatic skin.

PMID- 9602866
TI  - Peripheral blood lymphocytes from psoriatic patients are hyporesponsive to beta
      streptococcal superantigens.
AB  - The strong association of acute guttate psoriasis and streptococcal throat
      infection, together with the preferential use of T cells expressing a particular
      T-cell receptor, has suggested a role for bacterial superantigens in the
      pathogenesis of psoriasis. We examined the proliferative responses of peripheral
      blood lymphocytes (PBLs), obtained from patients with psoriasis and from healthy
      controls, to streptococcal superantigens, cytoplasmic membrane-associated protein
      (CAP) and secretion-type CAP (SCAP), isolated from group A, beta-haemolytic
      streptococci. PBLs from patients with psoriasis showed significantly less
      response to SCAP and CAP than those from healthy controls. Because there was no
      difference between psoriatic patients and controls in the proliferative response
      of PBLs to staphylococcal enterotoxin A or E (SEA, SEE) or the mitogen
      phytohaemagglutinin (PHA), these findings strongly suggest that the reduced
      reactivity to the streptococcal superantigens seems to reflect anergy of a
      population of PBLs to the superantigens. As the CAP used in the present study
      stimulates V beta 8 T cells selectively, we further examined the proliferation of
      V beta 8 T cells after such stimulation using flow cytometry. V beta 8 T cells
      obtained from three of four psoriatic patients failed to proliferate in the
      presence of CAP, whereas they proliferated vigorously in the presence of SEE,
      which activates V beta 8 T cells, confirming the specific hyporesponsiveness of
      PBLs from psoriatic patients to streptococcal superantigens. We then determined
      the effects of serum factors on the suppressed response of PBLs to the
      streptococcal superantigens with SCAP or CAP. It was partially restored when PBLs
      were cultured with sera obtained from healthy subjects, although the responses
      were still significantly lower than those of the healthy controls. In contrast,
      psoriatic sera markedly suppressed the proliferative response of PBLs from
      healthy controls to CAP or SCAP, but showed no suppression of the proliferative
      response of PBLs to SEA. Because these findings suggest the presence of specific
      inhibitory factors in psoriatic sera, we examined whether the inhibitory effect
      was caused by antisuperantigen antibody. However, no significant increase was
      detected in antibody titre to CAP in psoriatic sera, as has been noted in sera
      from patients with poststreptococcal glomerulonephritis. The present results show
      for the first time the hyporesponsiveness of PBLs to streptococcal superantigens
      and the presence of serum inhibitors that specifically inhibit T-cell response to
      the superantigens in psoriatic patients. These findings suggest a pathological
      role for streptococcal infections in the pathogenesis of psoriasis.

PMID- 9602867
TI  - Effect of isotretinoin therapy on natural killer cell activity in patients with
      xeroderma pigmentosum.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized
      by sun sensitivity, defective DNA repair, markedly increased susceptibility to
      skin cancer, and a variety of immunological defects, including defective natural
      killer (NK) cell activity. Retinoid therapy has been demonstrated to protect
      effectively against the development of skin cancers in patients with XP, although
      its mechanism of action is unknown. We describe a series of eight XP patients,
      six of whom were given oral isotretinoin. The NK cell activity was not affected
      by low-dose isotretinoin, i.e. 0.5 mg/kg per day. However, higher doses of
      isotretinoin, e.g. 1.0 mg/kg per day, produced a significant decrease in NK cell
      function, at the same time as producing a reduction in the frequency of
      development of skin cancers. Retinoid therapy may have a skin cancer preventing
      effect by enhancing other immune effector mechanisms or via epithelial cell
      differentiation.

PMID- 9602868
TI  - Th2-like cytokine activity in dermatitis herpetiformis.
AB  - Dermatitis herpetiformis (DH) is a chronic subepidermal blistering disease, in
      which a perivascular cellular infiltrate, composed mainly of CD4+ T lymphocytes
      together with a varying number of neutrophils and eosinophils, is thought to be
      important in the pathogenesis of blister formation. The aim of this study was to
      investigate the potential role of cytokines such as the interleukins IL-4 and IL
      5 and to quantify the distribution of T cells as well as their state of
      activation using alkaline phosphatase-antialkaline phosphatase and reverse
      transcriptase-polymerase chain reaction (RT-PCR) procedures in seven patients
      with typical clinical and histological features of DH. A strong extracellular
      staining with anti-IL-4 monoclonal antibody was detected in the upper dermis with
      a prevalent perivascular pattern in perilesional areas, whereas in the dermal
      epidermal separation sites there was an intense, scattered distribution. IL-5 was
      intensely expressed, mainly at the intracellular level, by eosinophils and
      lymphocytes. Concerning RT-PCR, five DH patients showed a strong positive signal
      for both IL-4 and IL-5 cytokines while two patients showed a faint signal for
      both IL-4 and IL-5; these last two cases were histologically poor in inflammatory
      cells. In view of these results, it can be hypothesized that the recruitment of
      eosinophils and neutrophils in DH may be induced not only by granulocyte
      macrophage colony-stimulating factor and IL-8 as previously demonstrated, but
      also by Th2 cytokines as well.

PMID- 9602869
TI  - Neutrophilic urticaria: clinical features, histological changes and possible
      mechanisms.
AB  - Neutrophilic urticaria (NU) is a histologically defined entity, but its clinical
      and pathogenetic aspects are poorly understood. We investigated 22 NU patients
      whom we identified by examining 118 biopsies of weals. The patients comprised 11
      of 20 with acute urticaria, nine of 49 with chronic urticaria, one of 10 with
      cold urticaria and one of 10 controls undergoing prick tests. Clinically, NU
      patients had a shorter mean duration of disease than other urticaria patients and
      significantly increased erythrocyte sedimentation rate and leucocytosis.
      Histologically, not only neutrophil counts, but to a lesser extent also
      eosinophil counts and mononuclear cell infiltrates were significantly increased
      in lesional skin of NU, and there was more marked vasodilatation and endothelial
      swelling. On immunohistochemistry, increased tumour necrosis factor alpha and
      interleukin (IL)-3 expression was noted, compared with other urticarias, whereas
      IL-8 expression was only minor. These data characterize NU as an acute phase
      urticarial reaction associated with an intense inflammatory infiltrate and marked
      upregulation of some mast cell-derived cytokines.

PMID- 9602870
TI  - Comparison of calcipotriol monotherapy and a combination of calcipotriol and
      betamethasone valerate after 2 weeks' treatment with calcipotriol in the topical
      therapy of psoriasis vulgaris: a multicentre, double-blind, randomized study.
AB  - A clinical study was conducted to determine whether, in the topical treatment of
      psoriasis, a combination of calcipotriol and betamethasone valerate after
      previous treatment with calcipotriol alone was more effective than the
      continuation of the monotherapy with calcipotriol, especially in 'low
      responders'. Patients (n = 169) with the clinical diagnosis 'chronic plaque-type
      psoriasis' were treated twice daily for 2 weeks with calcipotriol, followed by a
      4-week treatment with calcipotriol monotherapy in 87 patients or combined
      calcipotriol/betamethasone valerate in 82 patients; all patients were followed
      for 8 weeks. The psoriasis area and severity index (PASI) was used to compare the
      two treatment groups. The overall therapeutic result was also assessed by the
      investigators and patients. The combination therapy was more effective, as
      assessed by all evaluated variables; moreover, patients showing insufficient
      response to calcipotriol alone after 2 weeks showed a regression of psoriatic
      lesions using the combination regimen. Thus, the combination of calcipotriol and
      topical steroids is recommended as the therapy of first choice for patients who
      do not respond well to treatment with 2 weeks of calcipotriol alone. Furthermore,
      this combination reduces the hazards associated with the long-term use of topical
      corticosteroids (atrophy and rebound) as well as the irritation associated with
      calcipotriol.

PMID- 9602871
TI  - The calcipotriol dose-irritation relationship: 48 hour occlusive testing in
      healthy volunteers using Finn Chambers.
AB  - Calcipotriol is widely used in the treatment of psoriasis. Adverse lesional and
      perilesional irritation may occur. Allergy may occasionally be suspected. Allergy
      patch testing with calcipotriol may be difficult or impossible because
      calcipotriol is a local irritant. The aim of the present study was to assess the
      calcipotriol dose-irritation relationship, and establish a non-irritant patch
      test concentration for calcipotriol allergy patch testing. The study was a
      prospective, double-blind, randomized, dose titration evaluation in 180 healthy
      volunteers never previously exposed to calcipotriol. All individuals were patch
      tested with a calcipotriol dilution series (range 0.016-250 micrograms/mL).
      Clinical reading of test sites and measurement of erythema using a Minolta
      ChromaMeter were performed on days 2 and 3. Laser Doppler perfusion imaging of
      cutaneous blood flow was performed on day 3. Doubtful reactions (score 1/2) and
      weak reactions (score 1) were frequent and observed even at low dose exposure.
      Reactions declined in strength between the readings on day 2 and day 3. Only
      score 2 reactions with moderate erythema and some infiltration showed a threshold
      of no irritation. This threshold was confirmed by colorimetry and flowmetry.
      Cases of suspected allergy to calcipotriol may to avoid irritant reaction and
      false positive readings, be patch tested with calcipotriol 2 micrograms/mL
      citrate-buffered isopropanol solution applied under occlusion for 48 h using
      small Finn Chambers. Score 1/2 and 1 reactions are likely to reflect irritation.
      A positive test should be repeated after a minimum period of 3 months to ensure
      its consistency over time. A repeated open application test may be indicated.

PMID- 9602872
TI  - An epidemiological study of the influence of season (cold and dry air) on the
      occurrence of irritant skin changes of the hands.
AB  - In the course of an ongoing cohort study on constitutional and occupational risk
      factors for the development of irritant hand dermatitis in hairdressing
      apprentices, an increased prevalence of irritant skin changes was noted in a
      subgroup examined during particularly cold winter months. Prompted by this
      observation, the importance of several meteorological factors (day means of
      temperature, relative and absolute humidity) was assessed in extensive
      statistical analyses based on data of 742 participants, supplemented by
      meteorological information obtained from the German Meteorological Service (DWD).
      There were significant associations of existing hand dermatitis with low
      temperature and low absolute humidity (Mann-Whitney U-test, P < 0.0001), but not
      with relative humidity (P = 0.38). Logistic regression analysis, including known
      determinants of irritant hand dermatitis in this setting, showed that low
      temperature and low relative humidity tended to be risk factors (OR = 1.66 and
      1.57, respectively, for the lower quartiles, P = 0.07 in both cases), and
      confirmed that absolute humidity significantly influenced the occurrence of
      irritant hand dermatitis (OR = 2.06 for < 4.8 mg/L, P < 0.01). Thus, these
      environmental factors must be regarded as possible confounders in the analysis of
      future epidemiological studies on irritant hand dermatitis and should be
      considered in multifactorial analyses.

PMID- 9602873
TI  - Latex allergy in health-care workers in an English district general hospital.
AB  - Immediate hypersensitivity to latex protein is a serious and potentially life
      threatening problem. This study found that eight of 867 (0.9%) medical and
      nursing staff in a district general hospital were allergic to latex with
      resultant hand eczema and/or urticaria. Wheezing occurred when latex became
      airborne, adsorbed to starch powder. Sensitized individuals are at risk of
      anaphylaxis when they themselves become patients. Measures to prevent latex
      sensitization include pre-employment advice regarding hand care and glove use,
      particularly for atopics, who are at increased risk. Gloves made from synthetic
      latex must be available for a sensitized individual, both to use at work and when
      undergoing medical examinations, surgery and dentistry. Increased awareness of
      the problem by health-care workers is important in order to recognize those at
      risk.

PMID- 9602874
TI  - Granulocyte/macrophage colony-stimulating factor increases wound-fluid
      interleukin 8 in normal subjects but does not accelerate wound healing.
AB  - Granulocyte/macrophage colony-stimulating factor (GM-CSF) is thought to play an
      important part under conditions of impaired wound healing. This is not confirmed
      and it is also unknown whether GM-CSF affects wound healing in healthy subjects.
      We conducted a randomized, double-blind, placebo-controlled pilot study in 10
      healthy volunteers. Triplicate wounds (10 x 10 x 0.5 mm) on the right and left
      upper thigh were made by a razor blade and injected with GM-CSF or a solvent
      control. Four of the 10 volunteers were re-examined after 2 months by
      investigating the healing of a new set of triplicate wounds injected with solvent
      control alone (controls). Factors measured were wound healing time, wound-fluid
      cytokines by enzyme-linked immunosorbent assay, wound-fluid inflammatory cells
      and dermal thickness by ultrasonography. Intradermal injection with 20 micrograms
      GM-CSF per wound caused significantly higher wound-fluid GM-CSF and interleukin 8
      (IL-8) levels than in controls, but did not affect the time needed for wound
      closure (mean 11 days in all groups), dermal thickness, wound-fluid inflammatory
      cells or other wound-fluid cytokines, e.g. vascular endothelial growth factor
      (VEGF) and platelet-derived growth factor (PDGF). Transforming growth factor
      (TGF) beta 1 and beta 2, epidermal growth factor (EGF), and beta-fibroblast
      growth factor (beta-FGF) were not measurable in any wound fluid. The lack of
      efficacy of exogenously delivered GM-CSF on wound healing in healthy subjects is
      probably based on the failure of GM-CSF to induce 'wound-healing cytokines' like
      PDGF, FGF, TGF, EGF or VEGF. However, GM-CSF increases IL-8 release, which is a
      potent chemotactic cytokine, indicating that GM-CSF might be of therapeutic value
      under conditions of impaired chemotaxis.

PMID- 9602875
TI  - Clinical accuracy of the diagnosis of cutaneous malignant melanoma.
AB  - Diagnostic accuracy for melanoma was determined in a dedicated pigmented lesion
      clinic. We assessed the impact of duration of experience in dermatology and also
      the relationship between tumour thickness and accuracy of clinical diagnosis. We
      reviewed the histopathology request forms and reports for all biopsies generated
      by the Pigmented Lesion Clinic, Western Infirmary, Glasgow during 1992-94
      inclusive. The clinic is staffed by two consultants, one senior registrar and one
      registrar. Diagnostic accuracy, index of suspicion, sensitivity, specificity and
      positive predictive value were calculated for the clinic overall, and for each
      grade of staff. One hundred and sixty-three lesions were diagnosed clinically as
      melanoma. A histopathological diagnosis of melanoma was made for 128 lesions
      during this period, 113 of which had been correctly diagnosed before surgery. The
      diagnostic accuracy for two dermatologists each with > 10 years experience in
      dermatology was 80%, with sensitivity of 91% and positive predictive value of
      86%. Diagnostic accuracy rates for two senior registrars (each with 3-5 years
      experience) and six registrars (each with 1-2 years experience) were 62% and 56%,
      respectively. Thin and intermediate thickness melanomas generated the greatest
      inaccuracy irrespective of clinical experience, although registrars failed to
      recognize melanoma three times more often than the other groups. We report the
      diagnostic accuracy for melanoma by trained dermatologists to be higher than
      previously reported. In comparison with trainees, > 10 years experience in
      dermatology and exposure to more than 10 melanomas per year appears to be
      associated with greater diagnostic accuracy. Knowledge of the current clinical
      diagnostic accuracy at varying levels of experience is essential if the impact of
      training is to be evaluated. As pigmented lesions of virtually all types can be
      treated within dermatology departments, dermatologists are the appropriate first
      point of referral for suspected early melanoma.

PMID- 9602876
TI  - Effect of heliotherapy on the cost of psoriasis.
AB  - A 2-year trial was conducted to evaluate the cost-effectiveness of heliotherapy
      for psoriasis. The course and cost of psoriasis of 46 Finnish patients were first
      closely monitored for 1 year, then the patients received a 4-week supervised
      heliotherapy treatment in the Canary Islands, Spain, after which they continued
      to be followed for another year. Heliotherapy dramatically reduced the severity
      of psoriasis and also seemed to have favourable long-term effects on psoriasis.
      The mean direct cost of the 4-week heliotherapy for one patient was FIM12,289 (1
      Pound = FIM7.0 in 1989). The cost of flights and half-board in Spain formed
      nearly 60% (FIM7033) of the total cost. In the year preceding heliotherapy, the
      mean direct annual cost of antipsoriasis therapy was FIM7335 and in the year
      after FIM5700, a reduction of 22% in annual costs; this change was not
      statistically significant because there were large variations in costs among
      patients. The costs of heliotherapy exceeded manyfold the mean monthly cost of
      conventional psoriasis therapy. There were no overall savings using heliotherapy
      in those patients suffering mainly from moderately severe psoriasis. Heliotherapy
      saved costs only in those patients with severe psoriasis that required expensive
      medication or ward treatment. Although heliotherapy cannot be regarded as an
      economical treatment for the average patients with psoriasis, it clears psoriasis
      effectively and is preferred by patients. Thus, heliotherapy constitutes an
      alternative for patients suffering severe psoriasis.

PMID- 9602877
TI  - A practical guide to topical therapy in children.
AB  - The parents of children with skin disease are often unsure how much topical
      therapy, particularly of corticosteroids, they should apply. The aims of this
      study were to devise simple guidelines on topical therapy for children, parents,
      doctors and nurses, and to check the accuracy of these guidelines in practice.
      The guidelines are based upon four principles: the adult fingertip unit (FTU);
      the 'rule of 9s'; standard height and weight charts for children; and standard
      nomograms for calculating body surface area. Twenty-four children (11 boys and 13
      girls) aged 6 months to 9 years 4 months with atopic eczema were recruited and
      the number of FTUs required to treat different anatomical areas calculated in
      accordance with the proposed guidelines. Ointment was applied and the number of
      FTUs needed for each area was recorded. The amount used was then compared with
      that predicted. No child required a greater number of FTUs than that predicted,
      and the number of FTUs predicted for each anatomical region was accurate to
      within 1 FTU. The guidelines provide a useful indication of how much topical
      therapy is required for children, and advice sheets have been prepared for
      children of different ages.

PMID- 9602878
TI  - Interleukin-12 expression in human afferent lymph derived from the induction
      phase of allergic contact dermatitis.
AB  - Recent reports suggest that production of interleukin-12 (IL-12) by dendritic
      cells and keratinocytes may play an important part in contact hypersensitivity
      reactions. In the present study we investigated mRNA and protein expression of IL
      12 in human skin lymph derived from normal untreated skin (n = 5) and from the
      induction phase of allergic contact dermatitis (CD) (n = 5). mRNA levels were
      determined at various time points in the lymph cells by a nested reverse
      transcriptase-polymerase chain reaction method. Time course analysis reproducibly
      revealed a constitutive expression of both IL-12 p40 and p35 mRNA in the
      migrating lymph cells in all volunteers. However, no enhancement of the IL-12
      mRNA signal was found during the induction phase of allergic CD. Furthermore, as
      determined by a sensitive ELISA technique, IL-12 protein was not detectable in 60
      lymph samples derived from normal untreated skin or in 68 lymph samples obtained
      during the induction phase of allergic CD at any time point of the lymph
      cannulation. In conclusion, our findings indicate that no significant protein
      levels of IL-12 are washed out from the skin into the afferent lymph or are
      produced and released by migrating lymph cells during the induction phase of
      allergic CD in vivo.

PMID- 9602879
TI  - The compliance of renal transplant recipients with advice about sun protection
      measures.
AB  - Renal transplant recipients have an increased risk of developing non-melanoma
      skin cancer. Ultraviolet radiation is one of the major cofactors in the
      development of skin cancer in the immunosuppressed. In view of this, we undertook
      this study to determine the advice given to renal transplant recipients and their
      compliance with that advice. Two hundred and two renal transplant recipients were
      interviewed using a questionnaire. Their knowledge about the risk of non-melanoma
      skin cancer and preventive measures was not good, despite advice and literature
      given to newly transplanted patients at the time of discharge from hospital. Only
      54% remembered receiving advice. Renal physicians and nurses gave advice to the
      majority, with dermatologists providing advice only in 17% of cases. The use of
      sun-protective measures such as sun avoidance and protective clothing was poor
      and the use of sun barrier creams was inappropriate. Only 30% of patients knew
      why extra precautions against sunlight were necessary. Health professionals and
      dermatologists in particular need to take a more active role in raising the
      awareness of renal transplant recipients to their increased risk of non-melanoma
      skin cancer.

PMID- 9602880
TI  - Lyme disease with facial nerve palsy: rapid diagnosis using a nested polymerase
      chain reaction-restriction fragment length polymorphism analysis.
AB  - A 64-year-old woman with Lyme disease and manifesting facial nerve palsy had been
      bitten by a tick on the left frontal scalp 4 weeks previously. Erythema migrans
      appeared on the left forehead, accompanied by left facial paralysis. Nested
      polymerase chain reaction-restriction fragment length polymorphism analysis
      (nested PCR-RFLP) was performed on DNA extracted from a skin biopsy of the
      erythema on the left forehead. Borrelia flagellin gene DNA was detected and its
      RFLP pattern indicated that the organism was B. garinii, Five weeks later, B.
      garinii was isolated by conventional culture from the erythematous skin lesion,
      but not from the cerebrospinal fluid. After treatment with ceftriaxone
      intravenously for 10 days and oral administration of minocycline for 7 days, both
      the erythema and facial nerve palsy improved significantly. Nested PCR and
      culture taken after the lesion subsided, using skin samples obtained from a site
      adjacent to the original biopsy, were both negative. We suggest that nested PCR
      RFLP analysis might be useful for the rapid diagnosis of Lyme disease and for
      evaluating therapy.

PMID- 9602881
TI  - Drug-induced linear IgA disease with antibodies to collagen VII.
AB  - Linear IgA disease (LAD) is characterized by circulating and tissue-bound IgA
      antibodies against heterogeneous antigens in the cutaneous basement membrane
      zone. In most cases the cause is unknown, but a minority of cases has been drug
      induced. We report a 76-year-old man who developed an acute blistering eruption
      following high-dose penicillin treatment for pneumococcal septicaemia. Indirect
      immunofluorescence demonstrated dermal binding IgA antibodies, and Western
      blotting of serum showed reactivity with a 250 kDa dermal antigen corresponding
      to collagen VII of anchoring fibrils. Indirect immunoelectron microscopy showed
      antibody labelling in the lamina densa and sublamina densa zone. This is one of
      the few cases of drug-induced LAD in which the target antigen profile has been
      characterized, and the first in which the antigen has been shown to correspond to
      collagen VII.

PMID- 9602882
TI  - Sporadic dystrophic epidermolysis bullosa with concomitant atopic dermatitis.
AB  - We describe a patient with sporadic dystrophic epidermolysis bullosa associated
      with well-documented atopic dermatitis. We discuss this case in relation to a
      newly described clinical subtype of epidermolysis bullosa known as epidermolysis
      bullosa pruriginosa, a dystrophic variant associated with prominent pruritus. The
      relations of this case of sporadic dystrophic epidermolysis bullosa with other
      dominantly inherited forms of dystrophic epidermolysis bullosa such as the Pasini
      variant, the pretibial variant, and Bart's syndrome are also discussed. The role
      of atopic dermatitis in exacerbating dystrophic epidermolysis bullosa in this
      patient raises an important consideration in the care of this group of patients.

PMID- 9602883
TI  - Skin signs in the diagnosis of thallium poisoning.
AB  - A 45-year-old man developed a painful and rapidly progressive sensory-motor
      polyneuropathy associated with confusion and convulsions. This resulted in
      hypoventilation and led to respiratory failure and coma. A rapid and diffuse
      alopecia occurred after 3 weeks in the intensive care unit. Examination of hair
      roots under polarized light detected dystrophic anagen hairs with dark bands
      caused by empty spaces in the disorganized cortex. These dark zones were
      originally reported in patients with thallium poisoning and a toxicological
      investigation confirmed thallium exposure. The classical systemic symptoms and
      the various dermatological signs are reviewed, and the origins of contamination
      and physiopathology discussed.

PMID- 9602884
TI  - Immediate-type heat urticaria: report of a case and study of plasma histamine
      release.
AB  - We report a 68-year-old man who had immediate-type heat urticaria with systemic
      symptoms. Immersing his hand in water at 42 degrees C (heat challenge test)
      produced an urticarial response, with an increase in the plasma histamine level
      from 0.26 to 7.64 ng/mL. Administration of oral antihistamines alone did not
      suppress either the urticarial response or the increase in plasma histamine.
      However, a combination of antihistamines and desensitization improved the skin
      lesions and reduced the plasma histamine level. The heat challenge test
      subsequently provoked a negative response and there was no increase in plasma
      histamine level 3 months after starting the combination therapy. These results
      indicate that the histamine level reflected the result of the heat challenge test
      and the amelioration of the skin eruption.

PMID- 9602885
TI  - Psoriatic arthritis associated with dilated cardiomyopathy and Takayasu's
      arteritis.
AB  - A 40-year-old Japanese man with psoriatic arthritis (PA) involving the spine,
      sacroiliac and peripheral joints presented with dyspnoea and ankle oedema. Blood
      pressure was 180/110 and 114/80 mmHg in the right and left upper arms,
      respectively. Examinations showed left ventricular dilatation and diffuse
      hypokinesis of the left ventricle, with no involvement of the coronary arteries.
      Aortography detected total occlusion of the left subclavian artery and stenosis
      of the origin at the right renal artery. Dilated cardiomyopathy and Takayasu's
      arteritis associated with PA was diagnosed. A few cases of PA have been reported
      in association with cardiovascular diseases, but the association of these three
      diseases has not been documented in the literature to date. Dermatologists need
      to be aware of cardiovascular manifestations in patients with PA, because
      cardiovascular diseases are not rare in other seronegative spondyloarthropathies.

PMID- 9602886
TI  - An indolent penile herpetic ulcer in a patient with previously undiagnosed human
      immunodeficiency virus infection.
AB  - We report a case of an atypical penile herpetic ulcer in a man with previously
      undiagnosed human immunodeficiency virus (HIV) infection. Swabs of the lesion
      were negative for herpes simplex virus (HSV) by culture and electron microscopy.
      However, histopathology of biopsy material showed characteristic herpetic
      multinucleate giant cells. Immunochemistry using polyclonal antibodies was
      positive for HSV1 and HSV2. The lesion completely resolved after treatment with
      aciclovir and the patient subsequently tested positively for HIV antibodies.

PMID- 9602888
TI  - Early curettage of giant congenital naevi in children.
AB  - Early curettage of giant congenital naevi in new-born infants, if performed
      during the first few weeks after birth, can have a substantial effect on the
      pigmentation of the lesions, reducing the number of pigmented cells and leaving
      only moderate scars. We describe our experience in a series of nine congenital
      naevi treated by curettage between the first and seventh week after birth.
      Histological changes that occur in the naevus during the first few days after
      birth mean that early treatment is needed to obtain a cosmetic improvement.
      Curettage as an early treatment for giant congenital naevi in new-born infants
      provides cosmetic improvement and might decrease the risk of malignancy; however,
      the lesions are not cured. Naevus cells persist in the deep dermal layers and may
      come to the surface, such that close monitoring is needed long after curettage.
      The cosmetic improvement is likely to benefit the child's psychological
      development.

PMID- 9602887
TI  - Pyoderma gangrenosum of the penis.
AB  - Two cases of pyoderma gangrenosum involving the penis are presented. Treatment
      was difficult in both cases despite the use of high doses of prednisolone. In one
      case, the addition of thalidomide proved successful, whereas in the other,
      minocycline effected a cure.

PMID- 9602889
TI  - Subcutaneous phaeohyphomycosis caused by Geniculosporium species; a new fungal
      pathogen.
AB  - A 70-year-old Japanese timberworker dealing with imported timber from the U.S.A.
      and Russia had an asymptomatic subcutaneous nodule with a small fistula on his
      left knee. Histopathological examination of the nodule revealed brownish hyphal
      elements in encapsulated pyogranuloma. The fungus isolated from a discharge of
      the fistula and an excised specimen of the lesion was identified as
      Geniculosporium sp., which represents a conidial state (anamorph) of several
      genera such as Anthostomella, Biscogniauxia, Euepixylon, Leprieuria, Nemania,
      Phylacia and Rosellina in the Xylariaceae. Whereas this dematiaceous hyphomycete
      is commonly found on decaying wood and bark of various trees, to our knowledge,
      this is the first case of a phaeomycotic cyst caused by fungi belonging to the
      genus Geniculosporium.

PMID- 9602890
TI  - Subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei in a patient with
      advanced tuberculosis.
AB  - We report a case of subcutaneous phaeohyphomycosis due to Exophiala jeanselmei in
      an 84-year-old Korean farmer suffering from pulmonary tuberculosis. He presented
      with six subcutaneous, fluctuant abscesses on the left distal forearm and wrist.
      Subcutaneous infections by E. jeanselmei mostly present as a solitary cyst or
      abscess on an extremity. The present case showed localized multiple abscesses
      suggesting metastatic tuberculous abscesses or other pyogenic bacterial
      infections.

PMID- 9602891
TI  - Cutaneous infection with Alternaria alternata complicating immunosuppression:
      successful treatment with itraconazole.
AB  - We report an immunosuppressed patient who presented with unusual leg ulceration
      caused by Alternaria alternata infection. Alternaria is a common saprophyte that
      is not usually pathogenic in humans. However, infections have previously been
      documented. Most cases occur in immunocompromised patients and the skin
      manifestations may vary considerably. The diagnosis is often missed initially as
      it is not frequently suspected. The treatment is controversial both in choice of
      agent used and in duration of therapy.

PMID- 9602892
TI  - Streptococcal impetigo induces Th1-preponderant activation of T lymphocytes with
      subsequent anergy to superantigenic exotoxins in patients with atopic dermatitis.

PMID- 9602893
TI  - Two populations of CD1a+ epidermal dendritic cells expressing B7 molecules in
      human skin.

PMID- 9602894
TI  - Metallothionein expression in tattooed skin.

PMID- 9602895
TI  - Perforating granuloma annulare complicating tattoos.

PMID- 9602896
TI  - Endothelin-secreting angiosarcoma occurring at the site of an arteriovenous
      fistula for haemodialysis in a renal transplant recipient.

PMID- 9602897
TI  - Does influenza vaccination induce bullous pemphigoid? A report of four cases.

PMID- 9602898
TI  - Pemphigus vulgaris with involvement of the cervix.

PMID- 9602899
TI  - The pustular eruption of ulcerative colitis: a variant of Sweet's syndrome?

PMID- 9602900
TI  - Unusual skin ulceration in an HIV-positive patient who had cutaneous syphilis and
      neurosyphilis.

PMID- 9602902
TI  - Pyoderma gangrenosum successfully treated with perilesional granulocyte
      macrophage colony stimulating factor.

PMID- 9602901
TI  - Autoerythrocyte sensitization syndrome with positive anticardiolipin antibodies.

PMID- 9602903
TI  - Cyclosporin for the treatment of granuloma annulare.

PMID- 9602905
TI  - Erbium: YAG laser-assisted treatment of miliary osteoma cutis.

PMID- 9602904
TI  - Intralesional treatment of cutaneous leishmaniasis with meglumine antimoniate.

PMID- 9602906
TI  - Chronic buccal ulceration induced by nicorandil.

PMID- 9602907
TI  - Workshop on the applicability of the ADI to infants and children: consensus
      summary.

PMID- 9602908
TI  - Toxicity testing and derivation of the ADI.
AB  - The ADI is an estimate of the amount of a chemical that can be ingested daily
      over a lifetime without appreciable health risk. It is derived from No-Observed
      Adverse-Effect-Levels (NOAELs) determined in a battery of toxicity tests in
      animals and augmented by human data where available. The toxicity tests are
      intended (with a few exceptions) to embrace all the circumstances of human
      exposure to dietary chemicals. Hence these tests include chronic studies,
      sometimes with prior exposure in utero, and reproduction tests covering the
      reproductive phase including effects on the parental animals and the offspring.
      The tests should also cover the rapid growth phase from weaning to maturing. The
      ADI is calculated from the lowest NOAEL in the most sensitive test and the most
      sensitive species, unless other data indicate otherwise, and if the reproductive,
      neonatal or rapid growth phases indicate particular periods of sensitivity this
      should drive the numerical derivation of the ADI. In calculating the ADI, the
      NOAEL is divided by appropriate arbitrary or data-derived safety or uncertainty
      factors. Care in selecting the pivotal test, the NOAEL and the safety factors
      should ensure that the ADI does apply to children (or other age groups). However,
      because of the higher food intake of children on a body weight basis, specific
      risk management measures may be needed to ensure that the ADI is not exceeded.

PMID- 9602909
TI  - Toxicokinetics in infants and children in relation to the ADI and TDI.
AB  - Age-dependent developmental changes in toxicokinetics occur in both rats and
      humans, particularly in relation to renal function and hepatic xenobiotic
      metabolism. These processes are immature in humans at birth, especially in the
      pre-term neonate, but mature rapidly over the first months of life. In
      consequence the duration of immaturity primarily corresponds to the period of
      suckling. Similar developmental changes occur in the neonatal rat over the first
      weeks of life. Rat pups start to consume some of the adult diet in the third week
      of life, prior to weaning, so that there is a potential for consumption of the
      adult diet during the period of immaturity. There is an extensive database on the
      pharmacokinetics of therapeutic drugs in infants and children. The
      elimination/clearance of many drugs is higher in children than in adults and this
      difference would apply to other xenobiotics. In consequence, children frequently
      will have lower body burdens than adults for the same daily intake of a chemical
      when this is expressed on a body weight basis, as used to describe the ADI
      (Acceptable Daily Intake) or TDI (Tolerable Daily Intake) (e.g. mg/kg body
      weight/day). Therefore, an increased safety or uncertainty factor for post
      suckling infants and children is not required in relation to age-related
      differences in toxicokinetics. Indeed, the higher clearance of many xenobiotics
      (toxicokinetics) by children compared with adults may compensate, at least in
      part, for increased organ sensitivity (toxicodynamics) during development.

PMID- 9602910
TI  - Susceptibility in utero and upon neonatal exposure.
AB  - Important determinants or principles in developmental toxicology are: (1)
      genotype; (2) developmental stage when an insult is hitting; (3) mechanisms of
      action; (4) pharmacokinetics of the drug in the mother, conceptus and the
      neonate; (5) the manifestations of embryo/foeto- and neonatal toxicity such as
      death, malformations, growth inhibition and functional disturbances; and (6) dose
      effect and dose-response relationships. The present paper will give a broad
      review of some important developmental events and sensitivity periods, such as
      the preimplantation period, the period of gastrulation, organogenesis and
      placental formation, the foetal and neonatal period during which xenobiotics can
      cause perturbation in the normal development. Mostly pharmaceuticals are used as
      examples due to their often well documented effects and sometimes known
      sensitivity periods. For the postnatal period, some neurotoxic pesticides and
      environmental pollutants, known to affect adult behaviour in experimental animals
      after perinatal exposure, are given as examples.

PMID- 9602911
TI  - Onset of xenobiotic metabolism in children: toxicological implications.
AB  - The level of expression of cytochromes P450 shows a wide interindividual
      variability, depending on the age and tissue investigated. Several lines of
      evidence indicate that the human foetal liver is an active site for the
      biotransformation of drugs, chemicals and hydrophobic endogenous molecules.
      Besides this high degree of maturity, many studies have shown a discrepancy in
      the onset of activities and suggested that cytochrome P450 isoforms developed
      independently. Thus, many cytochromes P450 are absent or barely detectable in the
      foetal liver and develop postnatally. The postnatal evolution of P450 was
      explored in a liver bank constituted with samples collected from neonates aged
      less than 24 h to 10 years. Three major groups of cytochrome P450 could be
      described: a first group of cytochromes P450 expressed in the foetal liver
      includes the CYP3A7 and 4A1, mostly active on endogenous substrates; a second
      group (termed early neonatal P450) includes CYP2D6 and 2E1. They surged within
      hours after birth although proteins could not be detected in foetal samples. A
      third group of P450s (neonatal P450) develops later. CYP3A4 and CYP2Cs rose
      during the first weeks after parturition and CYP1A2 was the last isoform to be
      expressed in the human liver. Among phase II enzymes, epoxide hydrolase and
      glutathione S-transferase pi are very active in the foetal liver, whereas
      glutathione S-transferases mu and alpha and UDP-glucuronosyltransferases develop
      within 3 months after birth. These data clearly emphasize the delayed maturation
      of certain biotransformation pathways in the human liver during the perinatal
      period and constitute a scientific basis for improving safety during chemical
      exposure in children.

PMID- 9602912
TI  - Research needs: recommendations of an ILSI Working Group on age-related
      differences in susceptibility.
AB  - Research needed to better understand the similarities and differences between
      children and adults in their inherent susceptibilities to toxicants is briefly
      outlined. The focus is on cancer, immune system effects, and neurotoxicity. A
      full report of the ILSI Working Group that developed these recommendations is
      available from the ILSI Risk Science Institute.

PMID- 9602913
TI  - Developmental toxicology: adequacy of current methods.
AB  - Toxicology embraces several disciplines such as carcinogenicity, mutagenicity and
      reproductive toxicity. Reproductive toxicology is concerned with possible effects
      of substances on the reproductive process, i.e. on sexual organs and their
      functions, endocrine regulation, fertilization, transport of the fertilized ovum,
      implantation, and embryonic, fetal and postnatal development, until the end
      differentiation of the organs is achieved. Reproductive toxicology is divided
      into areas related to male and female fertility, and developmental toxicology.
      Developmental toxicology can be further broken down into prenatal and postnatal
      toxicology. Today, much new information is available about the origins of
      developmental disorders resulting from chemical exposure. While these findings
      seem to promise important new developments in methodology and research, there is
      a danger of losing sight of the precepts and principles established in the light
      of existing knowledge. There is also a danger that we may fail to correct
      shortcomings in our existing procedures and practice. The aim of this
      presentation is to emphasize the importance of testing substances for their
      impact in advance of their use and to underline that we must use the best
      existing tools for carrying out risk assessments. Moreover, it needs to be
      stressed that there are many substances that are never assessed with respect to
      reproductive and developmental toxicity. Similarly, our programmes for post
      marketing surveillance with respect to developmental toxicology are grossly
      inadequate. Our ability to identify risks to normal development and reproduction
      would be much improved, first if a number of straightforward precepts were always
      followed and second, if we had a clearer understanding of what we mean by risk
      and acceptable levels of risk in the context of development. Other aims of this
      paper are: to stress the complexity of the different stages of normal prenatal
      development; to note the principles that are applicable in developmental and
      especially prenatal toxicology; to describe the different agents that might act
      as developmental toxicants or teratogens; to show the broad scope of different
      effects caused by developmental toxic agents; and to indicate methods to detect
      and to recognise causes of developmental defects with the primary objective of
      preventing these disorders.

PMID- 9602914
TI  - The applicability of the ADI (Acceptable Daily Intake) for food additives to
      infants and children.
AB  - Children are not little adults. Children may respond differently from adults
      because they are in a state of growth and development; or because of differences
      in toxicokinetics or toxicodynamics. Infants and children are often assumed to be
      more susceptible to toxic effects, but this generalization is founded on
      assumptions rather than on facts. Available data are mostly concerned with
      toxicity and therapeutic effects of pharmaceuticals, while the effects in
      children of industrial chemicals are less well documented. Childhood is
      characterized by growth and development. Toxicants may interfere with these
      processes, and therefore toxic exposure may have more serious consequences for
      children than for adults, irrespective of sensitivity. Immature physiological
      functions of the foetus and young child theoretically make these age groups more
      vulnerable to toxicants, at least up to 1 year of age. The existing data on
      effects of chemical exposure in children point in the direction that
      susceptibility depends on the substance and on the exposure situation. For a
      particular compound children may be more sensitive than adults, or they may be
      less sensitive. Further, the sensitivity of children to a particular substance
      varies greatly with age. It is necessary to view premature neonates, neonates,
      infants, and children of different ages as separate risk groups. The long-term
      studies used as the basis for establishing ADIs cover lifetime for laboratory
      animals. Methods which have special emphasis on reproductive cells, on the
      foetus, and on the immature organism are used. Taken together, these studies
      cover exposure during all life stages. However, some specific types of effects,
      and delayed effects of perinatal exposure are not always included in standard
      toxicity test protocols. Exposure may also differ between children and adults.
      The food intake of children is qualitatively and quantitatively different form
      that of adults, and the EU Scientific Committee for Food has recommended that
      intake assessment of children be considered separately from that of adults
      because patterns of consumption are different. The ADI should cover the entire
      population including children. Special considerations regarding the use of food
      additives do apply to infants below the age of 12 weeks, who depend entirely on
      infant formula for nutrition.

PMID- 9602915
TI  - Different dietary patterns in relation to age and the consequences for intake of
      food chemicals.
AB  - This paper principally addresses the question of whether exposure to food
      additives/contaminants is likely to be higher in children than adults. Food
      consumption surveys conducted in the United Kingdom indicated that 99% of infants
      were receiving some solid food at 6 months of age (mean age of introduction 13
      weeks), mainly 'family' foods not specifically produced for infants. On a body
      weight basis, young children, age 1 1/2-4 1/2 years, were shown to consume more
      than adults most notably of dairy products, puddings and confectionery (up to
      five times adult intakes) and of soft drinks (up to 16 times adult values). Two
      examples of risk assessments are given, for chlorinated dibenzodioxins and
      saccharin, where the intake was highest in children, in some cases exceeding the
      Provisional Tolerable Weekly Intake or Acceptable Daily Intake, respectively. The
      necessary risk management measures taken are discussed.

PMID- 9602916
TI  - The ADI as a basis to establish standards for pesticide residues in food products
      for infants and children.
AB  - Pesticides are widely used in agriculture to control a variety of detrimental
      organisms. As a consequence, low but measurable amounts of residues may be found
      in the food supply including food intended for infants and young children. This
      has been the cause of some alarm since it is difficult for the general public to
      understand the magnitude of health risk associated with the consumption of food
      contaminated with low levels of potentially toxic chemicals. In this context
      safety-based regulations for pesticide residues that ensure the protection of
      infants and young children are of crucial importance. In this article we discuss
      the applicability of the ADI to infants and children with regards to pesticides
      and outline a proposal which has been devised to establish residue limits for
      finished baby food products.

PMID- 9602918
TI  - Oral cadmium exposure of adults in Germany. 2: Market basket calculations.
AB  - The cadmium intake of adults in Germany was calculated within the framework of
      market basket studies. Data were available on cadmium content of representative
      food assortments from 1988 and 1991. Food intake data were obtained within the
      second MONICA (MONItoring trends and determinants in CArdiovascular disease)
      survey 1988 and the nutrition survey in the new Federal lands 1991/92. Combining
      both data sets, an average cadmium intake of adults was found to be in the range
      10-14 micrograms/day. This cadmium intake is 16-19% of the Provisional Tolerable
      Weekly Intake (PTWI) for cadmium and a toxicological risk from orally consumed
      cadmium can be excluded. The results were comparable to literature values.
      Cadmium intake was higher in men than in women owing to their higher food
      consumption. No differences were observed between cadmium intake in 1988 and
      1991. The relative contribution of different food groups to cadmium consumption
      amounted to: bread, cake and pastries, 41%; potatoes, 14%; vegetables, 10%; meat,
      sausage and fish 9%.

PMID- 9602917
TI  - A database for environmental contaminants in traditional foods in northern and
      Arctic Canada: development and applications.
AB  - The potential health effects of environmental contaminants in traditional food
      has become a concern among northern communities because of the presence of
      environmental contaminants in the Arctic ecosystem. Exposure assessments are
      needed but they require comprehensive dietary information and contaminant data.
      Over the last 10 years, there has been considerable effort to monitor the level
      of contaminants in fish and wildlife collected from different regions in northern
      and Arctic Canada. The development of a database and its application for dietary
      contaminant exposure assessment are described. We conducted an extensive
      literature review on levels of environmental contaminants in northern and Arctic
      Canada. The ranges of levels of four contaminants of major concern (chlordane,
      mercury, polychlorinated biphenyls and toxaphene) in 81 species of marine
      mammals, terrestrial mammals, birds, fish and plants are summarized. These data
      represent 69% of the 117 species of fish, wildlife and plants mentioned in our
      dietary interviews conducted in the northern communities. A significant
      percentage of the foods had contaminant levels exceeding the guidelines used by
      Health Canada for market food consumed by the 'southern' populations. Mathematic
      modelling of the distributions of the data showed that contaminant levels in most
      food groups are log-normally distributed and have a typical coefficient of
      variation of about 100%. Examples are presented to demonstrate the use of the
      data for contaminant exposure assessment. Average contaminant exposure levels
      estimated using the database for two communities are comparable to those obtained
      previously using community specific data. With the current knowledge of
      environmental contaminant levels in the northern traditional food system, it may
      be feasible to conduct preliminary risk assessment of dietary exposure of
      environmental contaminants when some diet information for a community is
      available. Further sampling and analysis may be needed only for confirmation
      purposes.

PMID- 9602919
TI  - Organochlorine pesticides, polychlorinated biphenyls and dioxins in human milk
      from Swedish mothers.
AB  - Ten human milk samples, collected from two towns, Uppsala and Sundsvall, in
      Sweden in 1994 were analysed for selected chlorinated pesticides (HCB, alpha- and
      gamma-HCH, DDT, DDD and DDE) and PCB congeners (PCBs 28, 77, 101, 105, 118, 126,
      138, 153, 156, 158, 167, 169 and 180), PCDDs and PCDFs. The levels found in this
      study, including the toxic equivalent (TEQ) values, showed a slight downward
      trend between 1986 and 1994 and are somewhat lower than levels reported from
      other countries. The contribution of both the mono- and non-ortho PCBs, together
      with that of PCDD/Fs to the total TEQ values was assessed. Over 70% of the TCDD
      equivalents was derived from PCBs, PCB 126 being the major contributor. Other
      high PCB contributors were PCBs 156 and 118. The levels of HCB, alpha- and gamma
      HCH, and sigma DDT were generally higher in Uppsala than in Sundsvall. They were,
      however, over 50% lower in 1990 than in 1986 and have since changed little. For
      the PCDD/Fs the results show a marked decrease (ca 50%) in levels between 1986
      and 1994. There is an indication that PCB 153 and PCB 126 may be good indicators
      for total PCB and TEQ levels respectively.

PMID- 9602920
TI  - Application of an enzyme-linked immunosorbent assay for screening of sheep urine
      and animal tissue for the androgenic steroid trenbolone acetate in the State of
      Kuwait.
AB  - This study was undertaken to determine the presence of any residue-positive meat
      and urine samples from live sheep in the State of Kuwait market by using an
      enzyme-linked immunosorbent assay (ELISA) method and to examine the accuracy and
      precision of the method. A total of 350 samples, including 230 sheep urine, 30
      beef meat and 90 chicken, were subjected, after extraction, to an ELISA for the
      determination of their contents of the androgenic hormone, trenbolone acetate.
      The results obtained showed that the trenbolone acetate levels in the urine
      ranged from 0.1 to 0.9 ng/ml and in the muscle tissue from 0.02 to 0.05 ng/g all
      of which are below the maximum residue levels accepted (2.0 ng/g) by FAO/WHO. The
      mean recovery and CV, respectively, ranged from 36.7% and 5.8 (spiking level to
      0.2 ng/g) to 49.6% and 10.4 (spiking level 1.5 ng/g). These results were
      confirmed by gas chromatography-mass spectrometry analysis (GC-MS). Based on the
      data obtained, it was concluded that ELISA can be used safely for screening
      purposes, however, any suspect sample must also be analysed by GC-MS to exclude
      any false positive identifications.

PMID- 9602921
TI  - The effect of cooking on veterinary drug residues in food: 7. Ivermectin.
AB  - The stability to heat and cooking of ivermectin was investigated. The drug was
      insufficiently soluble in water to allow the effect of heating in simple aqueous
      solutions to be studied. The effect of a range of cooking processes was
      investigated on pig muscle and liver, cattle muscle and liver and salmon muscle.
      The drug was found to be stable to the effect of cooking. Some leaching of
      ivermectin with juices as they exuded from the foods as they were cooked was
      observed; in one case this amounted to about 50% of the total residue.

PMID- 9602922
TI  - Contamination of animal feedingstuffs with undeclared antimicrobial additives.
AB  - A study was carried out on 397 feedingstuffs and 11 premixes on which 161 (39.5%)
      were declared free of medication and 247 (60.5%) were medicated. These were
      subjected to analysis for the presence of antibiotics. Of the 247 medicated feeds
      87 (35.2%) contained undeclared antimicrobials of which 59 (23.9%) were at a
      concentration sufficient to allow quantification by HPLC. Of the 161 unmedicated
      feeds 71 (44.1%) were shown to contain detectable antimicrobials of which 42
      (26.1%) contained concentrations which could be quantified by HPLC. The most
      frequently identified contaminating antimicrobials were chlortetracycline (CTC)
      (15.2%), sulphonamides (6.9%), penicillin (3.4%) and ionophores (3.4%). Four
      samples (ionophores--3, sulphadimidine--1) contained therapeutic concentrations
      and one sample a supra-therapeutic concentration (monensin). The remainder were
      sub-therapeutic. All the contaminating concentrations of sulphadimidine detected
      were sufficient to cause violative tissue residues if fed to animals immediately
      prior to slaughter.

PMID- 9602923
TI  - 4-Hexylresorcinol as inhibitor of shrimp melanosis: efficacy and residues
      studies; evaluation of possible toxic effect in a human intestinal in vitro model
      (Caco-2); preliminary safety assessment.
AB  - Studies were performed on the efficacy, residues and in vitro enterocyte toxicity
      of 4-hexylresorcinol (4-HR), which could be utilized as an inhibitor of shrimp
      melanosis (black spot). Mediterranean sea shrimp (Parapaeneus longirostris) were
      treated with solutions of 4-HR in sea-water, at three different concentrations,
      25, 50 or 100 mg/kg of shrimp, to test its antioxidative property. As a
      comparison a group of shrimp was treated with sodium metabisulphite (1 g/kg),
      while another group was left untreated. 4-HR showed a marked ability to inhibit
      or slow down melanosis (black spot) in shrimp; the most effective concentration
      was 100 mg/kg within an optimum period of 7 days but with effects up to the tenth
      day. During the first 5 days, 4-HR residues in the edible part of the shrimp
      showed a fast decrease in all three groups, going from initial average values of
      20 mg/kg at 0 time, to 0.9 in the group treated at 25 mg/kg; from 42 to 1.8 mg/kg
      in the group at 50 mg/kg and from 85 to 1.9 mg/kg in the group at 100 mg/kg. In
      vitro studies on enterocyte-like Caco-2 cells did not indicate any cytotoxic
      effect up to a concentration of 50 micrograms/ml. Moreover, no inhibition of
      protein synthesis was observed, which lends further support to the absence of
      significant damage to the intestinal mucosa induced by 4-HR. The available
      database on 4-HR pharmacology and toxicology is inadequate to determine even a
      provisional ADI. There is negative evidence of carcinogenesis and no significant
      untoward effects were observed in humans when it was used as an anthelmintic.
      However, it is not possible to determine a NOEL for non-genotoxic effects. 4-HR
      could become an interesting alternative to the use of sulphites to prevent black
      spot. However, a more complete database is needed to achieve a regulatory
      evaluation.

PMID- 9602924
TI  - Evaluation of the black light test for screening aflatoxin-contaminated maize in
      the Brazilian food industry.
AB  - The results of the black light test for aflatoxin-contaminated maize carried out
      in a large food factory in the State of Sao Paulo was evaluated against bi
      directional thin layer chromatography (TLC) analysis for 286 samples of maize.
      All 286 samples were accepted by the black light test (< 7 fluorescent points),
      however, the results from TLC analysis showed that 96 samples were contaminated
      and 14 showed aflatoxin B1 contamination levels higher than 20 micrograms/kg.
      There were 14 false negative results and no false positives and out of the 14
      samples, six did not show visible fluorescent points. If the rejection criterion
      of one or more fluorescent points were applied, the six samples would be accepted
      by the black light test. But, in this case, 95 samples would be rejected and 87
      results would be false positives because they did not have contamination levels
      over 20 micrograms/kg which is the acceptance limit of the black light test. The
      results indicate that the black light test, as utilized by this factory, was not
      able to indicate lots with possible contamination and the black light test, as
      recommended in the literature, would produce a high number of false positives. It
      is necessary to make more studies on the use of black light as a screening test
      for possible aflatoxin B1-contaminated maize.

PMID- 9602925
TI  - Mycotoxins in ingredients of animal feeding stuffs: III. Determination of
      mycotoxins in rice bran.
AB  - Methods used previously for the determination of aflatoxins B1, B2, G1 and G2,
      ochratoxins A and B, cyclopiazonic acid, zearalenone, sterigmatocystin, and
      moniliformin in maize were applied successfully to rice bran. However, recovery
      of deoxynivalenol and other trichothecene mycotoxins spiked into samples was
      lower than expected and no citrinin could be recovered. Forty samples of rice
      bran used in the animal feed industry were examined for the presence of 20
      mycotoxins. The level of contamination of rice bran by mycotoxins was low.
      Aflatoxin B1 was present in 29 (72.5%) samples, usually together with related
      aflatoxins, up to a total of 28 micrograms/kg after allowing for recovery losses.
      Ochratoxin A at a level of 12 and 3 micrograms/kg was confirmed in two samples,
      while most samples also appeared to contain small concentrations of ochratoxin A.
      A chromatographic peak corresponding to cyclopiazonic acid occurred in several
      samples and one sample appeared to contain a low level of moniliformin. Positive
      confirmation of these last two mycotoxins was difficult and these findings must
      be regarded with caution. No other toxins were detected.

PMID- 9602926
TI  - Relationships between processing-structure-migration properties for recycled
      polypropylene in food packaging.
AB  - In this work the relationships between processing, structure and migration
      properties of recycled polypropylene (PP) were analysed in relation to the
      possible use of recycled PP in food packaging applications. PP containers used in
      food packaging were contaminated with food and then washed, reduced into a
      processable size, dried and reprocessed by injection moulding. Gel Permeation
      Chromatography (GPC) analysis, mechanical, and total migration tests were
      performed on injection moulded samples to verify the effect of the recycling
      process on the structure and properties of PP. In order to evaluate the effect of
      the molecular weight on the properties of the recycled polymer, the study was
      conducted on containers produced by injection moulding made from a low molecular
      weight (LMW) PP and on containers produced by thermoforming made from a high
      molecular weight (HMW) PP.

PMID- 9602927
TI  - Migration of epoxidized soya bean oil from plasticized PVC gaskets into baby
      food.
AB  - Expoxidized soya bean oil (ESBO) is used as a plasticizer in PVC gaskets in lids
      for glass jars used for packaging of ready-cooked baby food. The migration of
      ESBO from the lids has been determined in 81 samples of different dishes of baby
      food, including purees of beef, pork, fish, poultry, berries and vegetables. The
      level of ESBO in baby food has been determined using a gas chromatography/mass
      spectrometry (GC/MS) analytical procedure with a detection limit of 1.5 mg/kg.
      Residues of ESBO were found in all dishes except in blueberries. The levels
      ranged from < 1.5 to 50.8 mg/kg, with a mean of 11.9 mg/kg and a median of 7.8
      mg/kg in food with detectable levels. Expoxidized fatty acids may also occur
      naturally in food. Baby food which had never been in contact with the lids was
      therefore analysed and no detectable levels of diepoxidized C18-methylester,
      which was used for the determination of ESBO, were found. That demonstrates that
      the presented levels of ESBO in the baby food are only due to migration from the
      lids and not of natural origin.

PMID- 9602928
TI  - Studies on the permeation of inorganic salts through plastic films.
AB  - Permeation tests were carried out under several conditions for various metal
      ions, anions, temperatures and solvents. The study was designed as lag-time
      experiments where the amount of metal penetrating through the polymer was plotted
      against time. Diffusion and permeability coefficients were measured using the
      time-lag technique and by calculating the permeation rate. Graphite furnace
      atomic absorption spectroscopy was used to quantify the amounts of metal ions.
      Permeation of inorganic salts through low density polyethylene (LDPE) showed a
      strong dependency on the solvent used. With water as solvent, no permeation was
      measurable even at 60 degrees C, while ethanol, 1-propanol and 2-propanol gave
      increasing permeation. Small amounts of water in pure ethanol diminished the
      permeation rate considerably. Chloride salts led to the fastest diffusion,
      whereas bromide salts gave the highest permeation rate. Acetates and nitrates
      show virtually no permeation. In ethanol, copper chloride permeated faster than
      iron, zinc, cobalt, nickel or lithium chloride, and only tin chloride diffused
      faster than copper chloride. Reasons for the observed permeation behaviour are
      assumed to be the molecular size of an undissociated molecule, the degree of
      dissociation and the solvation in a solvent.

PMID- 9602929
TI  - Effects of packaging and storage conditions on volatile compounds in gas-packed
      poultry meat.
AB  - Volatile compounds released by raw chicken legs packed in modified atmosphere
      packages were determined in order to develop a spoilage indicator for monitoring
      the shelf-life of raw chicken. Internal spoilage indicators would react with
      compounds released during chemical, enzymatic and/or microbial spoilage
      reactions. The effects of four packaging factors (headspace volume, oxygen
      transmission rate of the package, residual oxygen and carbon dioxide
      concentration) and three storage factors (temperature, illumination and storage
      time) on the amounts of volatile compounds in the headspace of gas packages
      containing two chicken legs were studied. Statistical experimental design was
      applied and a linear screening design comprising 18 experiments (fractional
      factorial) was utilized. Volatile compounds in package headspace were determined
      by gas chromatography--mass spectrometry using the dynamic headspace technique.
      The results were compared with the results of sensory evaluation and microbial
      determinations. The head-space of stored packages was dominated by the following
      compounds: butene, ethanol, acetone, pentane, dimethylsulphide, carbon disulphide
      and dimethyl disulphide. In modelling, some interaction terms and squared terms
      were needed in addition to linear terms. The main factors affecting the amounts
      of ethanol, dimethyl sulphide, carbon disulphide and dimethyl disulphide were
      storage time and temperature. Other factors had only minor importance, carbon
      dioxide concentration and headspace volume being the most significant package
      parameters. The same four factors also had the greatest effects on the odour of
      chicken legs.

PMID- 9602930
TI  - In vitro study of TMAO reduction by Shewanella putrefaciens isolated from cod
      fillets packed in modified atmosphere.
AB  - A strain of Shewanella putrefaciens was isolated from cod fillets in a modified
      atmosphere (60% CO2, 30% O2, 10% N2). The effect of pH on the growth of
      Shewanella putrefaciens and TMAO reduction was studied in fish extract with
      citrate buffer systems at pH values from 5.8 to 6.8. The effect of the modified
      atmosphere (CO2, O2) on the growth of S. putrefaciens and on the reduction of
      TMAO to TMA was studied using solid media from fish extract packed under variable
      mixtures of CO2, O2 and N2. All the samples were incubated at 7 degrees C for 7
      days. Slow development of S. putrefaciens and no production of TMA was observed
      in fish extract buffered at pH 5.8. Inclusion of O2 in packaging atmosphere of
      solid fish extract, even at small proportions (10%), was inhibitory for the
      reduction of TMAO, while there was no effect of O2 on the growth of S.
      putrefaciens. Increased levels of CO2 (> or = 50%) in the atmosphere were
      inhibiting the growth of S. putrefaciens and consequently the production of TMA.

PMID- 9602931
TI  - Titanium: a promising new material for food contact. A study of titanium
      resistance to some aggressive food simulants.
AB  - It is well known that titanium is one of the most rugged metals; therefore it has
      been extensively used in many critical fields. However, the lowering of price and
      an increased availability of titanium has made this material suitable to be used
      in other industrial fields, such as the food industry. The present paper reports
      the results of an assessment that concludes that titanium could be regarded as a
      candidate food-grade material.

PMID- 9602932
TI  - Ethanol content of various foods and soft drinks and their potential for
      interference with a breath-alcohol test.
AB  - A variety of breads and soft drinks were tested and found to contain low
      concentrations of alcohol. The potential for these products to generate false
      readings on an evidential breath-alcohol instrument was evaluated. Alcohol-free
      subjects ingested these products and then provided breath samples into a
      DataMaster. It was found that breath samples provided immediately after
      consumption of some of these products, or with them still present in the mouth,
      did produce low levels of apparent breath alcohol, which may or may not be
      rejected as invalid by the breath-test instrument. If the subject swallowed or
      expectorated the food or beverage and then observed a 15-min deprivation period
      during which nothing was introduced into the mouth, the apparent effect was
      eliminated. These findings emphasize the need for the mandatory pretest alcohol
      deprivation period and the benefits of duplicate breath sampling.

PMID- 9602933
TI  - Lack of association between urinary creatinine and ethanol concentrations and
      urine/blood ratio of ethanol in two successive voids from drinking drivers.
AB  - The relationship between urinary ethanol concentration, urine/blood ratio of
      ethanol, and urinary creatinine content was investigated by the analysis of two
      successive voids from 40 individuals apprehended for driving under the influence
      of alcohol (DUI) in Sweden. The first specimen of urine was collected 24 +/- 17
      min (mean plus or minus standard deviation) before sampling blood, and the second
      specimen was collected 46 +/- 30 min after blood sampling. The mean blood-alcohol
      concentration (BAC) was 2.21 +/- 0.76 g/L, and the corresponding concentrations
      in the urine (UAC) were 2.88 +/- 1.08 g/L for the first void and 2.68 +/- 1.01
      g/L for the second void. The mean urine/blood ratios of ethanol were 1.31 +/-
      0.21 for the first void and 1.20 +/- 0.11 for the second void; the difference of
      0.11 +/- 0.24 was statistically significant (t = 3.08, p < 0.01). The
      concentrations of creatinine in urine from DUI suspects were 0.72 +/- 0.64 g/L
      for the first void and 0.86 +/- 0.73 g/L for the second void; there was no
      significant difference (t = 1.45, p > 0.05). The urinary creatinine content in
      specimens from drunk drivers was significantly less than the first morning voids
      from 3313 prison inmates (1.78 +/- 0.74 g/L). No significant correlations existed
      between UAC and urinary creatinine content (r = -0.14) between urine/blood ratios
      of ethanol and urinary creatinine (r = -0.19). However, the concentrations of
      ethanol in blood and urine were highly correlated; they were r = 0.94 +/- 0.055
      (p < 0.001) for first void and r = 0.96 +/- 0.045 (p < 0.001) for the second
      void. This study demonstrates that the relative dilution of urine specimens, as
      reflected in creatinine content, is not associated with the concentration of
      ethanol in the urine samples or with the UAC/BAC ratio.

PMID- 9602934
TI  - Dramatic signal reduction in ion-mobility spectrometry by residues of solvents.
AB  - During our evaluation of ion-mobility spectrometry (IMS) screening for the abuse
      of the beta-agonist clenbuterol during fattening in cattle, we found that
      clenbuterol could not be detected with the instrument in extracts obtained by
      solid-phase extraction or ion-pair extraction, although the recovery for these
      procedures was at least 85%. Several experiments showed that the signal loss
      occurred mainly during the evaporation of the organic solvent. Again, it could be
      shown that no clenbuterol was lost during this step. On further investigation, we
      found that so-called solvent residues, which are left after the evaporation of
      the organic solvent, caused a significant reduction of the clenbuterol signal.
      Other reagents used in our sample pretreatment procedures were also found to
      reduce the signal. For example, the signal reductions caused by the different
      reagents used for the ion-pair extraction of clenbuterol from human urine were
      determined. We think that IMS is only useful for our purpose if a chromatographic
      preseparation is performed.

PMID- 9602935
TI  - Determination of flunitrazepam and its main metabolites in serum and urine by
      HPLC after mixed-mode solid-phase extraction.
AB  - A rapid and sensitive method is presented for the simultaneous determination of
      flunitrazepam, norflunitrazepam, 7-aminoflunitrazepam, and 7
      acetamidoflunitrazepam in serum, plasma, and urine. The compounds were extracted
      by a mixed-mode solid-phase procedure following analysis by high-performance
      liquid chromatography and ultraviolet detection and using methylclonazepam as the
      internal standard. The method revealed high recoveries and showed good precision
      and linearity for all compounds. The limit of detection was at least 1 ng/ml
      serum (plasma) for all compounds.

PMID- 9602936
TI  - Determination of chlorpyrifos, chlorpyrifos oxon, and 3,5,6-trichloro-2-pyridinol
      in rat and human blood.
AB  - Analytical methods to quantitate chlorpyrifos and two potential metabolites,
      chlorpyrifos oxon (oxon) and 3,5,6-trichloro-2-pyridinol (TCP), in human and rat
      blood are described. Chlorpyrifos and the oxon were extracted simultaneously with
      a methanol/hexane mixture from 0.5 mL blood that was deactivated with an acidic
      salt solution. The extract was then concentrated and analyzed by negative-ion
      chemical ionization gas chromatography-mass spectrometry (NCI-GC-MS). TCP was
      extracted from a separate 0.1-mL aliquot of blood, also deactivated by the
      addition of acid. The t-butyldimethylsilyl derivative of TCP was formed using
      MTBSTFA, and the analysis was performed by NCI-GC-MS. Stable isotope analogues of
      chlorpyrifos (-13C2-15N), oxon (-13C2-15N), and TCP (-13C2) were used as internal
      standards. Oxon was observed to partially degrade to TCP during the sample
      analysis. Accurate oxon and TCP measurements were obtained with the use of oxon
      13C2-15N, TCP-13C2, and TCP-13C2-15N internal standards, which compensated for
      both the degradation of oxon and the formation of artifactual TCP during
      analysis. The limits of quantitation were 1 ng/mL blood for both chlorpyrifos and
      oxon and 10 ng/mL for TCP. Calibration curves were linear over the concentration
      range of 2.5-2500 ng/mL solvent for chlorpyrifos and oxon and between 5 and 1060
      ng/mL solvent for TCP. Taking concentration factors and extraction efficiencies
      into account, these linear ranges represent blood concentrations of approximately
      0.3-300 ng/mL blood for chlorpyrifos and the oxon and 6-1300 ng/mL blood for TCP.
      The lowest spike level for chlorpyrifos and the oxon was 1 ng/mL blood, and the
      lowest spike level for TCP was 10 ng/mL blood. Recoveries from rat blood were as
      follows: 106-119% for chlorpyrifos, 94-104% for oxon, and 85-102% for TCP. In
      addition, chlorpyrifos and oxon were incubated with rat and human blood for
      various time intervals before deactivation to determine precautions that needed
      to be taken when collecting and handling specimens. No change in chlorpyrifos
      concentration was observed in rat blood up to 180 min at 37 degrees C. In
      contrast, the oxon was rapidly hydrolyzed to TCP in both rat (t 1/2 approximately
      10 s) and human (t 1/2 approximately 55 s) blood held at 37 degrees C. The
      hydrolysis rate for the oxon was independent of whether a rat had been
      administered chlorpyrifos previously, the initial oxon concentration, the
      presence of chlorpyrifos, and the age or gender of the human volunteers. These
      results suggest rapid sample preparation is critical for accurate determinations
      of the oxon metabolite of chlorpyrifos. These methods provide excellent tools for
      use in chlorpyrifos pharmacokinetic modeling studies.

PMID- 9602937
TI  - Gas chromatographic method for the simultaneous determination of S-p
      toluylmercapturic acid and S-phenylmercapturic acid in human urine.
AB  - An analytical method for the simultaneous determination of S-p-toluylmercapturic
      acid (p-TMA) and S-phenylmercapturic acid (PMA) in human urine is described. PMA
      is a common biomarker for benzene exposure, whereas p-TMA is detected for the
      first time in the urine of workers occupationally exposed to toluene. Before
      analysis, the acidified urine samples were spiked with S-(p-fluorine)
      phenylmercapturic acid as internal standard. After extraction with ethyl acetate
      and derivatization with diazomethane, the methylethers were detected by gas
      chromatography coupled with mass selective detection. The criteria of reliability
      were satisfactory. The imprecisions within the series and from day to day were in
      a range from 4.9 to 13.4%, and the detection limits were 1 microgram/L for PMA
      and 5 micrograms/L for p-TMA. The application of the method to urine samples of
      32 subjects exposed to a median external concentration of 63 ppm toluene resulted
      in a median p-TMA excretion of 20 micrograms/L. However, no p-TMA was detected in
      the urine of subjects without occupational exposure to toluene. The determination
      of arylmercapturic acids is also suitable for biological monitoring of mixed
      exposures to toluene and benzene.

PMID- 9602938
TI  - Identification and determination of opipramol metabolites in plasma and urine.
AB  - In six cases of suspected opipramol overdose, commercially available immunoassays
      for tricyclic antidepressants (TCA) EMIT tox serum Assay and ADxR serum TCA Assay
      indicated arbitrarily high or toxic TCA concentrations. However, opipramol
      concentrations determined by high-performance liquid chromatography (HPLC)
      analysis were in the high-normal or low-toxic range. This finding prompted us to
      study opipramol metabolism by mass spectral techniques and to determine the cross
      reactivity of opipramol and its metabolites in immunoassays. Three previously
      unknown metabolites (I, II, V) included an oxidation product of the hydroxyethyl
      moiety to an acetic acid group at the piperazine side chain (1), a
      decarboxylation product of the latter metabolite (II), and opipramol-N-oxide (V).
      In addition, two previously reported metabolites were identified, which included
      a deshydroxyethyl metabolite (III) and dibenzazepine (IV). One of the major
      metabolites of opipramol is the acetic acid metabolite (I), which may exceed the
      opipramol plasma concentration immensely and contribute to an arbitrarily high
      concentration in commercially available immunoassays. The cross-reactivities of
      the metabolite (I) were determined to be 64 and 66% with EMIT and ADx,
      respectively.

PMID- 9602939
TI  - Cocaine, nicotine, caffeine, and metabolite plasma concentrations in neonates.
AB  - The objective of this study was to measure the umbilical cord plasma levels of
      cocaine, nicotine, caffeine, and their metabolites. Thirty-six neonates at risk
      for prenatal cocaine exposure were prospectively enrolled. Umbilical cord plasma
      was analyzed by gas chromatography-mass spectroscopy for cocaine, cocaethylene,
      benzoylecgonine (BZE), nicotine, cotinine, and caffeine. Eighteen neonates were
      plasma positive for BZE, and 50% of these were also positive for cocaine.
      Cocaethylene was not found. The maximum plasma cocaine concentration was 88 ng/mL
      (mean, 39 ng/mL). The maximum plasma BZE concentration was 3880 ng/mL (mean, 844
      ng/mL). Among BZE-positive babies, the mean plasma drug levels were as follows:
      nicotine, 1.8 ng/mL; cotinine, 94 ng/mL; and caffeine, 1205 ng/mL. Among the BZE
      negative babies, the mean plasma drug levels were as follows: nicotine, 5.2
      ng/mL; cotinine, 97 ng/mL; and caffeine, 1440 ng/mL. These cocaine levels raise
      the possibility of pharmacological effects of cocaine in the early neonatal
      period.

PMID- 9602940
TI  - Background levels of bromide in human blood.
AB  - A total of 183 random, whole-blood specimens was collected from healthy
      individuals within the State of Queensland (Australia), and the bromide
      concentration was determined by wavelength-dispersive X-ray fluorescence
      spectrometry (WDXRF). The intensity of the tube Compton scatter line was used to
      account for differences in matrices between the aqueous calibration standard and
      whole-blood specimens. Technical details of the WDXRF method are included in the
      experimental section of the paper. The overall mean for bromide in human blood
      was 5.3 +/- 1.4 mg/L and ranged from 2.5 to 11.7 mg/L. Associations between
      bromide levels and variables including age, gender, weight, height, and postcode
      address were examined by ANOVA and Pearson's correlation. Data indicate that aged
      persons (45-65+ years) are more likely to have higher bromide levels than younger
      persons (15-25 years). Our results also suggest differences in bromide levels
      between the sexes in similar age groups. Average levels were higher in females in
      most age groups. The reason for this difference requires further detailed
      investigation. No correlation was observed between bromide levels and height or
      weight of donors. No significant differences in bromide levels were found in
      persons living in the highly populated southeast region of Queensland compared
      with those living in the less urbanized northern parts of the state.

PMID- 9602941
TI  - Dose-concentration relationships in hair from subjects in a controlled heroin
      maintenance program.
AB  - Hair specimens were collected from the vertex area of 20 subjects taking part in
      a heroin-maintenance program. Subjects were administered, under controlled
      conditions, heroin hydrochloride in 2 or 3 doses/day intravenously. Heroin doses
      ranged from 30 to 800 mg/day, and were self-administered. In all cases, a 4-cm
      segment from the proximal zone (root) was analyzed, which corresponded to about
      100 days of hair growth. During that period, total heroin administered ranged
      from 14,100 to 71,540 mg. All special features of hair such as coloring,
      bleaching, etc. were noted. Each sample was washed twice with dichloromethane (5
      mL, 2 min) and, after drying, cut into small pieces of approximately 1 mm. A 30
      35-mg aliquot was incubated overnight at 45 degrees C in 1 mL methanol in the
      presence of 200 ng of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. The
      methanolic extract was then evaporated to dryness, and the residue was
      derivatized by silylation (BSTFA + 1% TMCS). Drugs were analyzed by gas
      chromatography-mass spectrometry in electron impact mode. Limits of quantitation
      were set to 0.1 ng/mg. Concentrations ranged from 0 to 4.53, 0.38 to 10.11, and
      0.71 to 5.20 ng/mg for heroin, 6-acetylmorphine, and morphine, respectively. 6
      Acetylmorphine was the major analyte present in hair in all but five cases.
      Heroin was present in the highest concentration in three cases, and morphine was
      the major metabolite in two cases, probably because of hydrolysis. Subjects
      tested positive for heroin in all but two cases. No correlation between the doses
      of administered heroin and the concentrations of total opiates in hair was
      observed (r = 0.346). However, when considering a single analyte, it was observed
      that the correlation coefficient seemed to be linked to its plasma half-life. A
      weak correlation coefficient corresponds to a drug with a short plasma half-life,
      and the correlation coefficient increases when plasma half-life increases, as r =
      0.12, 0.25, and 0.64 for heroin, 6-acetylmorphine, and morphine, respectively.
      These results suggest that using quantitative drug measurements in hair to
      determine the amount of drug ingested will remain inapplicable until more is
      known about the factors that may influence the incorporation of drugs into hair
      and a way to reduce the observed variability.

PMID- 9602942
TI  - GC and GC-MS determination of fluoroacetic acid and phenoxy acid herbicides via
      triphasal extractive pentafluorobenzylation using a polymer-bound phase-transfer
      catalyst.
AB  - A simple and sensitive gas chromatography and gas chromatography-mass
      spectrometry (GC-MS) procedure has been developed for fluoroacetic acid (FA) and
      phenoxy acid herbicides (PAHs) via triphasal extractive pentafluorobenzylation.
      The triphasal system consisted of an aqueous sample, the extraction solvent
      toluene containing pentafluorobenzyl bromide as the derivatization reagent, and
      polymer-bound tri-n-butyl-methylphosphonium bromide as a phase-transfer catalyst,
      FA spiked in beverages, such as orange juice and milk, was extracted as its
      pentafluorobenzyl (PFB) derivative under moderate conditions (i.e., at a pH value
      of 6.5 at 60 degrees C). The detection limits were 0.10-0.20 microgram/mL by GC
      with electron-capture detection (GC-ECD), and 0.42-0.50 microgram/mL by full-scan
      GC-MS. PAHs were also detectable in the same manner within the detection limits
      of 0.05-0.10 microgram/mL by GC-ECD and 0.13-0.25 microgram/mL by full-scan GC
      MS. Urine and serum which both contained 2,4-dichlorophenoxyacetic acid could
      also be analyzed by GC-MS after the triphasal pentafluorobenzylation. The
      detection limit was 0.20 microgram/mL in the full-scan mode and 10 ng/mL in the
      selected ion monitoring mode both for the urine and serum.

PMID- 9602943
TI  - Unusual death attributed to the combined effects of chloral hydrate, lidocaine,
      and nitrous oxide.
AB  - A case in which the death of a 2-year-old male child was the result of an acute
      intoxication with chloral hydrate, lidocaine, and nitrous oxide is presented.
      Trichloroethanol (TCE), the primary metabolite of chloral hydrate, was
      qualitatively detected by the Fujiwara reaction. Quantitation of TCE was carried
      out by gas chromatography-mass spectrometry (GC-MS) with the following results:
      plasma, 79.0 mg/L; urine, 31.0 mg/L; gastric contents, 454.0 mg/L; bile, 111.0
      mg/L; vitreous, 40.2 mg/L; cerebrospinal fluid (CSF), 68.3 mg/L; and liver, 164
      mg/kg. Lidocaine was quantitated by GC analysis using nitrogen-phosphorus
      detection with the following results: plasma, 11.9 mg/L; urine, 3.7 mg/L; gastric
      contents, 15.3 mg/L; bile, 19.0 mg/L; vitreous, 17.8 mg/L; CSF, 9.4 mg/L; and
      liver, 19.0 mg/kg. Nitrous oxide was quantitated in the blood with a value of 4.4
      mL/L.

PMID- 9602944
TI  - Analysis of fenthion in postmortem samples by HPLC with diode-array detection and
      GC-MS using solid-phase extraction.
AB  - Fenthion (O,O-dimethyl-O-[3-methyl-4-(methylthio)-phenyl]-thiophos-phate ) is an
      organophosphate insecticide. A specific method to quantitate fenthion in
      postmortem matrices with solid-phase extraction combined with high-performance
      liquid chromatography-diode-array detection (HPLC-DAD) and gas chromatography
      mass spectrometry (GC-MS) is presented. Fenitrothion (O,O-dimethyl-O-[3-methyl-4
      nitrophenyl]-thiophosphate) is selected as the internal standard. For sample
      cleanup, a simple but selective solid-phase extraction is chosen after comparison
      with traditional liquid-liquid extraction procedures. Homogenized and
      appropriately diluted aqueous samples are applied, and the analytes are desorbed
      with 5 mL of dichloromethane. Aliquots of the extract are used for HPLC-DAD and
      GC-MS analysis, Liquid and GC conditions are as follows: gradient elution with a
      mixture of methanol and water (10:90 to 90:10, v/v) containing 0.0125M NaOH on an
      Aluspher RP-Select B column monitoring at 250 nm, and temperature programming
      from 60 to 300 degrees C on a dimethylpolysiloxane column in the SCAN mode,
      respectively. This method is applied to a suicidal case involving unsuspected
      acute intoxication with fenthion (concentration in blood, 3.8 micrograms/mL).

PMID- 9602945
TI  - Comparison of fentanyl concentrations in unembalmed and embalmed liver samples.

PMID- 9602946
TI  - Buflomedil is a potent interfering substance in immunoassays of tricyclic
      antidepressants.

PMID- 9602947
TI  - Improved procedure for overcoming nitrite interferences in GC-MS procedures for
      cannabinoids.

PMID- 9602948
TI  - Mass-to-charge ratio misassignments of molecular ions in ion-trap mass
      spectrometry.

PMID- 9602949
TI  - The sodium-calcium ion membrane exchanger: physiologic significance and
      pharmacologic implications.
AB  - The Na(+)-Ca2+ exchanger is a non-ATP-dependent protein that, under steady-state
      conditions, extrudes Ca2+ from the interior of the cell into the extracellular
      space via facilitated transport. The activity of the exchanger seems to be
      reduced in myocardial ischemia, leading to increased intracellular Ca2+ in the
      ischemic heart, which can result in arrhythmia, myocardial stunning, and
      necrosis. In contrast, congestive heart failure and myocardial hypertrophy are
      associated with increased exchanger activity and a decreased inotropic state.
      Pharmacologic agents are being developed to modulate sodium ion levels in the
      cell, which could enhance or reduce sodium-calcium exchange as needed in various
      pathophysiologic states. At this time there are no available drugs that act
      specifically on the Na(+)-Ca2+ exchanger itself. The exchanger has been cloned,
      and inhibitory peptides of the exchanger may soon be available for possible use
      in treatment of congestive heart failure.

PMID- 9602951
TI  - Independence and statistical inference in clinical trial designs: a tutorial
      review.
AB  - The requirements for statistical approaches to the design, analysis, and
      interpretation of experimental data are now accepted by the scientific community.
      This is of particular importance in medical studies where public health
      consequences are of concern. Investigators in the clinical sciences should be
      cognizant of statistical principles in general, but should always be wary of the
      pursuing their own analyses and engage statisticians for data analysis whenever
      possible. Examples of circumstances that require statistical evaluation not found
      in textbooks and not always obvious to the lay person are pervasive. Incorrect
      statistical evaluation and analyses in such situations will result in erroneous
      and potentially serious misleading interpretation of clinical data. Although a
      statistician may not be responsible for any misinterpretations in such
      unfortunate circumstances, the quote often cited about statisticians and "damned
      liars" may appear to be more truth than fable. This article is a tutorial review
      and describes a common misuse of clinical data resulting in an apparently large
      sample size derived from a small number of patients. This mistake is a
      consequence of ignoring the dependency of results, treating multiple observations
      from a single patient as independent observations.

PMID- 9602950
TI  - Pharmacokinetics and pharmacodynamics of ranitidine in neonates treated with
      extracorporeal membrane oxygenation.
AB  - The pharmacokinetics and pharmacodynamics of ranitidine were studied in 13 term
      neonates with stable renal and hepatic function who were treated with
      extracorporeal membrane oxygenation (ECMO). Ranitidine was initially administered
      as a single 2 mg/kg dose over 10 minutes and intragastric pH was monitored to
      determine response. Within 90 minutes after administration of ranitidine,
      intragastric pH for all of the patients whose initial reading was < or = 4 had
      increased to > 5. Intragastric pH remained > 4 for a minimum of 15 hours. Mean +/
      1 standard deviation elimination half-life was 6.61 +/- 2.75 hours, and 41.5 +/-
      22.2% of the single dose was eliminated in urine within 24 hours. Total plasma
      clearance of ranitidine correlated well with estimated glomerular filtration
      rate. Twenty-four hours after the initial dose, a continuous infusion of
      ranitidine (2 mg/kg/24 hr) was started and continued for 72 hours or until ECMO
      was discontinued. Eleven patients completed 48 hours of continuous infusion and
      seven completed all 72 hours. Plasma clearance and elimination half-life were
      determined from steady-state plasma ranitidine concentrations 24, 48, and 72
      hours after the start of the infusion. There were no significant differences in
      clearance between these intervals. These data suggest that for term neonates with
      stable renal and hepatic function, ranitidine does not need to be administered
      more frequently than every 12 hours. A continuous infusion of 2 mg/kg/24 hours
      maintained intragastric pH above 4 in more than 90% of our patients, and in our
      opinion is the preferred method for delivering ranitidine to term neonates
      undergoing ECMO who require H2 antagonists. Response to therapy should be
      monitored by repeated measurement of gastric pH and the dose should be adjusted
      accordingly.

PMID- 9602952
TI  - Urine drug screening results from volunteers in phase I clinical pharmacology
      studies: are we being misled?
AB  - The general intent of phase I clinical pharmacology studies is to demonstrate the
      safety and tolerability of investigational new drugs in healthy human volunteers.
      There is emerging evidence that people who volunteer for these studies are not
      always truthful with investigators during the screening process. All healthy
      volunteers who participate in studies at the SmithKline Beecham Clinical
      Pharmacology Unit in Philadelphia, Pennsylvania, are required to submit to urine
      drug testing. During 11 months of 1996, a total of 1,469 urine samples were
      collected and tested for eight different drugs or classes of drugs of abuse. The
      urine samples collected during the first five months of 1996 were all analyzed
      using EMIT (Syva Corporation) and interpreted according to the guidelines
      established by the National Institutes of Drug Abuse (NIDA). Of 534 samples, 12
      (2.2%) were reported as positive. During the last 6 months of 1996, a new
      methodology using a fluorescence polarization immunoassay (FPIA) was used. This
      assay had lower limits of quantification than EMIT, and more stringent
      interpretation guidelines than those of the NIDA were used. Of 935 samples
      analyzed by FPIA, 89 (9.5%) were positive. Of the 89 positive test results, 59
      were below the cut-offs specified by the NIDA guidelines and would have been
      reported as negative. Interpretation of urine drug screen results according to
      the NIDA guidelines is not acceptable for clinical pharmacology investigations.

PMID- 9602953
TI  - Balanced designs in longitudinal population pharmacokinetic studies.
AB  - A simulation study was performed using a balanced design to determine the sample
      size required for accurate and precise estimation of a parameter at a given level
      of intersubject variability in a longitudinal population pharmacokinetic study. A
      two-compartment model parameterized in terms of clearance (Cl), volumes of the
      central (V1) and peripheral (V2) compartments, and intercompartmental clearance
      (Q) with multiple intravenous bolus inputs was assumed. Six samples were obtained
      from each subject using the informative profile (block) randomized design.
      Variability (in terms of coefficient of variation, CV) in model parameters was
      varied between 30% and 100%, and residual variability was fixed at 15%. Sample
      sizes ranging from 30 to 1,000 subjects were studied, and a hundred replicate
      data sets were generated and analyzed with NONMEM for each sample size at each
      CV. A sample size of 30 was required for accurate and precise estimation of
      structural model parameters when CV < or = 75%, except for Cl where it is
      adequate for CV < or = 100%. A sample size of 80 was required for intersubject
      variability estimation with CV < or = 60%. Robust estimates of variability in Cl
      were obtained with sample sizes of 30 (CV < or = 45%), 60 (CV 60-75%), and 100
      (CV > or = 75%). Positively biased estimates of residual variability were
      obtained irrespective of sample size at > or = 60% CV. This indicates that
      estimates of residual variability obtained in study situations where CV > or =
      60% should be interpreted with caution. In such situations model misspecification
      may not be the issue, because in this simulation study concentration-time
      profiles were generated and analyzed with the same model. Although these results
      should be interpreted within the context of the study, they provide a framework
      for addressing the issue of sample size in longitudinal population
      pharmacokinetic study with a balanced sampling design. The result of a population
      pharmacokinetic study can be anticipated by comparing the results of several
      simulations in which the various input factors have been varied.

PMID- 9602954
TI  - Absence of effect of terbinafine on the activity of CYP1A2, NAT-2, and xanthine
      oxidase.
AB  - Terbinafine is an allylamine antifungal agent used for the treatment of
      onychomycosis. It has previously been reported to interact with caffeine and is
      metabolized in part by the cytochrome P450 systems. This open-label, randomized,
      crossover study was conducted to examine the effect of terbinafine on the
      activity of cytochrome P450 1A2 (CYP1A2), N-acetyltransferase (NAT-2), and
      xanthine oxidase (XO). Twelve healthy nonsmoking adult volunteers were enrolled.
      Each received single doses of caffeine (100 mg), and urine was collected for a 16
      hour period with and without multiple-dose oral administration of terbinafine
      (250 mg daily for 3 days). Study periods were separated by a 4-week washout
      period. Urinary caffeine metabolite ratios were used to assess CYP1A2, NAT-2 and
      XO activity. Comparison of mean metabolic ratios for treatment with and without
      terbinafine indicated that terbinafine did not appear to alter the activity of
      CYP1A2, NAT-2, or XO, all of which regulate the biotransformation of caffeine.

PMID- 9602955
TI  - Effect of increasing gastric pH with famotidine on the absorption and oral
      pharmacokinetics of the inotropic agent vesnarinone.
AB  - The effect of famotidine, an H2 receptor blocker, on the oral absorption and
      pharmacokinetics of the novel agent vesnarinone was investigated after oral
      administration of 60 mg vesnarinone with and without pretreatment with
      intravenous famotidine. The single-blind, randomized, two-way crossover study was
      conducted in 12 volunteers, with a washout period of 7 days between the two
      treatments. A pH monitor was used to ensure that gastric pH of the subjects was <
      or = 3 in the absence of and > or = 5 in the presence of famotidine. A
      significant decrease in maximum concentration (Cmax) and increase in time to Cmax
      (tmax) was observed for vesnarinone during treatment with famotidine, whereas
      area under the concentration-time curve (AUC) was similar for both treatments.
      The physicochemical properties of the drug support the above observations.
      Therefore, therapies that increase gastric pH will affect the rate but not the
      extent of absorption of vesnarinone or the safety or efficacy profile of
      vesnarinone.

PMID- 9602956
TI  - Lack of effect of food on the oral bioavailability of irbesartan in healthy male
      volunteers.
AB  - This study was conducted to evaluate the effects of a high-fat meal on the oral
      bioavailability of an 300-mg irbesartan tablet in healthy male volunteers.
      Sixteen healthy young male volunteers participated in this single-center, open
      label, single-dose, crossover study. Each volunteer received a single 300-mg
      irbesartan tablet under fasted conditions and 5 minutes after a high-fat
      breakfast, with administrations separated by a 7-day washout period. Serial blood
      samples were collected over a 72-hour period, and plasma samples were analyzed
      for irbesartan using a validated high-performance liquid
      chromatography/fluorescence procedure. Food had no statistically significant
      effects on the peak concentration (Cmax) and area under the concentration-time
      curve (AUC) of irbesartan. The presence of food was associated with a slightly
      prolonged time to maximum concentration (tmax) and half-life (t1/2), but the
      differences were not statistically significant. The results of this study
      indicate that food does not affect the bioavailability of irbesartan. Thus,
      irbesartan can be administered without regard to meals.

PMID- 9602957
TI  - The effects of eprosartan, an angiotensin II AT1 receptor antagonist, on uric
      acid excretion in patients with mild to moderate essential hypertension.
AB  - The effects of antihypertensive agents, including angiotensin II receptor
      antagonists, on urine uric acid excretion may have important clinical
      consequences. Therefore, the effects of single and repeated doses of eprosartan
      on uric acid excretion were evaluated in 57 male patients with mild-to-moderate
      essential hypertension in a double-blind, randomized, placebo-controlled,
      repeated dose, dose-rising, two-period, period-balanced, crossover study
      conducted in two parts. In part 1 (n = 33), the effects of eprosartan dose
      regimens of 50 mg, 100 mg, and 350 mg once daily and 150 mg every 12 hours on
      uric acid excretion were assessed. In part 2 (n = 24), the effects of eprosartan
      dose regimens of 600 mg, 800 mg, and 1,200 mg once daily on uric acid excretion
      were assessed. Eprosartan was well tolerated. There were no appreciable changes
      from predose values in fractional excretion of uric acid (FEua), urine uric acid
      excretion, urine uric acid to creatinine (Uua/Ucr) ratios, or serum uric acid
      concentrations after single or repeated doses of eprosartan. Mean Uua/Ucr ratios
      for eprosartan doses of 50 mg, 100 mg, or 350 mg daily or 150 mg every 12 hours
      were comparable to those for placebo. Mean FEua values and Uua/Ucr ratios for
      eprosartan doses of 600 mg, 800 mg, or 1,200 mg daily also were comparable to
      those for placebo. Single and repeated oral doses of eprosartan ranging from 50
      mg to 1,200 mg daily had no effect on serum uric acid concentrations or urine
      uric acid excretion in patients with mild-to-moderate essential hypertension.

PMID- 9602958
TI  - Cough-challenge trial with a new angiotensin-converting enzyme inhibitor,
      imidapril.
AB  - This study was conducted to examine whether imidaprilat, an active diacid of the
      angiotensin-converting enzyme (ACE) inhibitor imidapril, preferentially inhibits
      angiotensin I degradation rather than bradykinin degradation, and whether
      imidapril is less active than other ACE inhibitors in inducing cough in patients
      with hypertension. The effect of imidaprilat on the inhibition of pressor
      response to angiotensin I and augmentation of depressor response to bradykinin
      was compared with that of enalaprilat and captopril in anesthetized rats. To
      determine the incidence of cough associated with imidapril, patients with a
      history of ACE inhibitor-induced dry cough were enrolled in a randomized, open
      labeled, crossover trial with two 6-week periods to be treated with imidapril or
      amlodipine, a calcium-channel blocker. The recurrence of cough was assessed
      during both treatments. In the animal study, there were no significant
      differences in the ratio of inhibition of pressor response to angiotensin I and
      the augmentation of depressor response to bradykinin among the ACE inhibitors. In
      the cough-challenge trial, a total of 60 patients with hypertension were enrolled
      in the study. Cough and cough related symptoms recurred in 98.3% of the patients
      (59/ 60) during imidapril therapy. In contrast, only two patients reported cough
      during treatment with amlodipine. These results indicate that imidapril has no
      selectivity in inhibiting angiotensin I- and bradykinin-degradation in rats, and
      that clinically it is not different from other ACE inhibitors in inducing cough
      in patients with hypertension.

PMID- 9602959
TI  - Analgesic dose-response relationship of ibuprofen 50, 100, 200, and 400 mg after
      surgical removal of third molars: a single-dose, randomized, placebo-controlled,
      and double-blind study of 304 patients.
AB  - The purpose of this single-dose, randomized, placebo-controlled, and double-blind
      study was to evaluate the analgesic dose-response relationship of 50-mg, 100-mg,
      200-mg, and 400-mg doses of ibuprofen after third molar surgery. Patients were
      instructed to take a single dose of either placebo or 50 mg, 100 mg, 200 mg, or
      400 mg of ibuprofen when the postoperative pain was moderate to severe.
      Acetaminophen 500 mg was used as a rescue medication. Pain intensity, pain
      relief, and any possible adverse events were recorded on self-administered
      questionnaires hourly for 6 hours after intake of study medication. If rescue
      medication was taken, the time of intake was registered. A total of 304 patients
      entered the study, and 258 complied with the protocol. A positive analgesic dose
      response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen was
      observed when evaluated by pain intensity difference, sum of pain intensity
      difference, pain relief, total pain relief, and survival distribution of patients
      not taking rescue medication. Although significant pain relief was seen after a
      dose of 50 mg ibuprofen, ibuprofen 400 mg provided maximum pain relief and the
      longest duration of analgesic effect. Mild transient adverse events were reported
      by 6.8% of the patients. However, there was no significant difference in
      frequency between the placebo and 50 mg, 100 mg, 200 mg, and 400 mg ibuprofen
      dose groups.

PMID- 9602960
TI  - Double-blind, single-dose comparison of bromfenac sodium, tramadol, and placebo
      after oral surgery.
AB  - This double-blind, parallel-group study was performed at a single site in
      patients with moderate or severe pain after oral surgery to remove one or more
      impacted third molars. Patients recorded their pain intensity at baseline and
      were then assigned to receive a single dose of bromfenac sodium (25 mg or 50 mg),
      tramadol (100 mg), or placebo, using a randomized double-blind code. At regular
      intervals for up to 8 hours after study drug administration, pain intensity and
      pain relief were recorded and were used to derive the efficacy variables, total
      pain relief (TOTPAR), pain intensity difference (PID), and summed pain intensity
      difference (SPID). Both doses of bromfenac were superior to tramadol and placebo
      in terms of hourly and peak pain relief and PID. The 3-hour and 8-hour TOTPAR and
      SPID results for both doses of bromfenac also were significantly superior to
      those for tramadol and placebo, whereas the scores for tramadol did not show
      superiority to placebo. Similarly, both doses of bromfenac were superior to
      tramadol and placebo as measured by patient global assessment, time to meaningful
      pain relief, and duration of pain relief. Bromfenac was well tolerated and was
      equivalent to placebo with respect to treatment-emergent study events. Overall,
      significantly more study events (total), digestive events (particularly nausea
      and vomiting), and nervous system events (particularly dizziness) occurred in
      patients treated with tramadol than in those in other treatment groups. Single
      oral doses of bromfenac were more effective, longer-acting, and better tolerated
      than single doses of tramadol in providing pain relief after oral surgery.

PMID- 9602961
TI  - The effect of cimetidine on the formation of sulfamethoxazole hydroxylamine in
      patients with human immunodeficiency virus.
AB  - Hypersensitivity reactions from trimethoprim/sulfamethoxazole are likely caused
      by a reactive nitroso intermediate formed from sulfamethoxazole hydroxylamine.
      This pilot study tested whether cimetidine inhibits the urinary excretion of
      sulfamethoxazole hydroxylamine. Ten outpatients infected with human
      immunodeficiency virus (HIV) and currently receiving
      trimethoprim/sulfamethoxazole prophylaxis were randomly selected from 59 eligible
      patients. Five received cimetidine 800 mg twice daily for 1 week and five served
      as controls. Two spot urine samples one week apart were obtained after a
      trimethoprim/sulfamethoxazole dose for all patients. Patients taking cimetidine
      had a significant decrease in excretion of sulfamethoxazole hydroxylamine
      relative to total excreted drug in the two urine samples compared with control
      patients. Cimetidine likely caused this decrease in sulfamethoxazole
      hydroxylamine excretion through inhibition of CYP3A4. Because of potential
      differences between HIV-infected patients and healthy subjects in oxidative
      metabolism, future studies of inhibitors of sulfamethoxazole hydroxylamine
      formation should be conducted in the HIV population.

PMID- 9602962
TI  - The influence of cimetidine on the disposition kinetics of the antidepressant
      venlafaxine.
AB  - The influence of cimetidine on the disposition pharmacokinetics of the
      antidepressant drug, venlafaxine, and its active metabolite, O
      desmethylvenlafaxine, was examined in 18 healthy young men and women. The steady
      state pharmacokinetic profiles of venlafaxine and O-desmethylvenlafaxine were
      evaluated during a 24-hour period after 5 days of treatment with venlafaxine (50
      mg three times a day) and during a second 24-hour period after 5 days of
      combination treatment with venlafaxine (50 mg three times a day) and cimetidine
      (800 mg once a day). The apparent oral clearance of venlafaxine decreased
      significantly in the presence of cimetidine and the average steady-state plasma
      concentration of venlafaxine increased significantly in the presence of
      cimetidine, but there were no changes in the corresponding concentrations of the
      active metabolite. However, O-desmethylvenlafaxine exhibits pharmacologic
      activity that is approximately equimolar to that of venlafaxine, and the sum of
      venlafaxine plus O-desmethylvenlafaxine plasma concentrations was increased by an
      average of only 13%. Therefore, the effect of cimetidine coadministration is not
      expected to result in clinically important alterations in the response to
      venlafaxine in patients with depression. This may not be true, however, for
      patients with compromised hepatic metabolic function.

PMID- 9602963
TI  - Written on behalf of the stiff finger.

PMID- 9602964
TI  - Wound repair.

PMID- 9602965
TI  - Tissue repair of the epidermis and dermis.
AB  - Wounds of the skin heal in a predictable fashion and at a fairly constant rate if
      impediments to healing can be avoided. For the skin wound of the hand, the
      therapist and surgeon face paradoxic demands to balance optimal immobilization
      for wound healing with optimal motion for function. As long as the wound remains
      stable, therapy can begin very early in the postoperative period without
      interruption of the wound-healing process.

PMID- 9602967
TI  - Peripheral nerve regeneration, repair, and grafting.
AB  - Peripheral nerve injuries are a major source of chronic disability. Advances in
      microsurgery and a better understanding of nerve healing have greatly improved
      the outcomes of nerve repair in the past two decades. This paper reviews the
      current thoughts on peripheral nerve regeneration and repair. Controversial
      topics such as the timing of nerve repair, new techniques of nerve repair (fibrin
      glue, lasers, and tubulization), nerve grafting, and the treatment of neuroma are
      discussed. A general approach to postoperative care is presented and shown to be
      governed by an understanding of not only nerve healing but tissue healing in
      general. A summary of current clinical results of upper extremity nerve repairs
      is given to provide benchmarks of practice for hand therapy units to achieve and
      supersede.

PMID- 9602966
TI  - Tendon repair.
AB  - Recent studies of tendon repair are reviewed in order to help hand therapists
      make the most effective decisions regarding treatment of tendon injuries. Flexor
      tendons are emphasized by inclusion of the most current discussions and research
      on the different phases of intrinsic and extrinsic healing, the zones of injury,
      mechanical and chemical influences on tendon healing, the techniques of tendon
      suturing, and the timing of repair and rehabilitation. The purpose of the article
      is to update hand therapists on the latest research efforts concerning tendon
      healing in order to achieve better functional outcomes following repair of these
      structures.

PMID- 9602968
TI  - Bony tissue repair.
AB  - Bone is among the most frequently injured of tissues, and bony injuries are among
      the conditions most commonly treated by hand therapists. An understanding of the
      biology of bony tissue repair, as well as the techniques available for its
      promotion, is therefore of the utmost importance to practitioners of hand
      therapy. This article addresses the biology of bony tissue repair, techniques
      currently available for the treatment of bony injuries, and management of
      specific bony injuries of the hand.

PMID- 9602969
TI  - How controlled stress affects healing tissues.
AB  - Restoration of a patient's full range of motion, strength, and function are the
      primary goals of occupational and physical therapy. Immobilization of normal
      connective tissue leads to biochemical, biomechanical, and physiologic changes
      within a week. These changes are magnified in the presence of trauma or edema,
      and they may create permanent damage if not addressed swiftly and properly. This
      is best accomplished by applying specific types of stress to the involved and
      associated structures at optimal intervals during the rehabilitation process.
      Load must be applied at adequate intensity and duration to successfully affect
      the viscous property of connective tissue. This is necessary to effect permanent
      elongation of the restricted tissues. Early controlled motion is vital to prevent
      the negative changes associated with immobilization and to maintain normal
      viscoelasticity and homeostasis of connective tissue. Hand therapists must have a
      thorough understanding of the changes associated with injured structures. Only
      then can they provide optimal stress delivery to facilitate restoration of
      function.

PMID- 9602970
TI  - Electrotherapy in tissue repair.

PMID- 9602971
TI  - The influence of ultrasound on healing tissues.
AB  - This paper identifies techniques in ultrasound that influence healing tissues.
      The importance of appropriate parameters is emphasized. Current literature is
      reviewed to support the use of ultrasound in specific conditions and different
      phases of healing. Types of wounds discussed include delayed-closure wounds, deep
      soft-tissue wounds, tendon and nerve repairs, bone fracture, and burn injury.
      There is a need for research in ultrasound directly related to hand therapy.

PMID- 9602972
TI  - Therapeutic effects of heat, cold, and stretch on connective tissue.
AB  - The anatomic architecture of connective tissue is dependent on the stresses
      associated with motion. Immobilization results in stress deprivation, causing
      structural changes in the tissue matrix. The structural changes that occur are
      due to the remodeling of tissue to its new resting length while being held
      immobile. The goal of remodeling stiffened, shortened tissues is to regain tissue
      length and promote unrestricted tissue gliding. The article reviews studies that
      examine the viscoelastic response of connective tissue to heat, cold, and
      stretch. An understanding of connective tissue response to these therapeutic
      interventions will enable clinicians to choose the appropriate modality and apply
      stretching techniques in a safe, efficient manner to enable patients to regain
      mobility.

PMID- 9602973
TI  - The influence of splinting on healing tissues.
AB  - In addition to immobilizing injured soft tissue to allow healing, splints are
      used to positively influence collagen remodeling through the application of low
      load forces to healing or contracted soft tissue, permitting soft tissue growth
      and concomitant increased function. When correction of limited passive range of
      motion due to soft tissue contracture is needed, splinting is an absolute
      requisite. No other currently available modality is able to hold a constant low
      load tension for a prolonged time sufficient to cause tissue growth.

PMID- 9602974
TI  - Hospital-acquired infection in elderly patients.
AB  - Increasing numbers of elderly people are being treated in hospitals and are at
      particular risk of acquiring infections. The incidence, risk factors and types of
      hospital-acquired infection (HAI) in the elderly are reviewed. Special reference
      is made to urinary tract infections, respiratory tract infections,
      gastrointestinal infections including Clostridium difficile, bacteraemia, skin
      and soft tissue infections and infections with antibiotic-resistant organisms.

PMID- 9602975
TI  - Microbiological monitoring of bone grafts: two years' experience at a tissue
      bank.
AB  - In the first two years of operation of a tissue bank, bone was processed on 63
      occasions from 22 cadaveric donors and on 37 occasions from 185 living donors. A
      standardized protocol for microbiological sampling, culturing and interpretation
      of the results was developed. Semi-quantitative culture of washings of bone was
      performed on receipt by the tissue bank, and broth enrichment cultures of bone
      samples were performed at the end of processing, and again after irradiation. One
      bone donation was rejected because of heavy contamination with Klebsiella sp. on
      receipt, and contamination of six donations with Burkholderia cepacia was shown
      to have come from a water deionizer. Contamination of bone on receipt by the
      tissue bank decreased during the study period, probably related to increasing
      experience of staff harvesting bone. Microbiological surveillance of bone grafts
      protect recipients from infection, and is useful as a quality control of the
      process of bone banking.

PMID- 9602976
TI  - Clinical experience and outcomes of community-acquired and nosocomial methicillin
      resistant Staphylococcus aureus in a northern Australian hospital.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a well-recognized cause of
      hospital-acquired sepsis. We reviewed the clinical features of a new variant of
      community-acquired MRSA originally described from the Kimberley region of
      northern Western Australia (WA MRSA). This strain has become an increasing cause
      of community- and hospital-acquired sepsis at Royal Darwin Hospital (RDH) in the
      Northern Territory, especially in Aboriginal Australians from remote communities.
      Fifty percent of WA MRSA was community-acquired, with 76% in Aboriginals. Like
      the MRSA from eastern Australia (EA MRSA), WA MRSA commonly caused skin sepsis
      but was less likely to cause respiratory or urinary infections compared with EA
      MRSA. Twelve out of 125 (9.6%) WA MRSA and 7/93 (7.5%) EA MRSA infections were
      septicaemias. Septicaemia due to WA MRSA occurred in adult medical patients,
      especially those with temporary haemodialysis catheters, while EA MRSA
      septicaemia occurred throughout the hospital. Aboriginal people were more likely
      to develop both community- and hospital-acquired WA MRSA septicaemia [overall
      relative risk (RR) 12.3 (95% CI 3.7-40.7)]. Control of WA MRSA requires policies
      to reduce transmission in both hospitals and communities. Community-based control
      programmes need support for individual patient management, improved housing and
      hygiene, control of skin sepsis and appropriate use of antibiotics, especially in
      rural Aboriginal communities in northern Australia.

PMID- 9602977
TI  - The action of three antiseptics/disinfectants against enveloped and non-enveloped
      viruses.
AB  - The antiviral action of chloroxylenol, benzalkonium chloride and
      cetrimide/chlorhexidine was assessed against a range of enveloped and non
      enveloped human viruses using a suspension test method. Viral suspensions of
      10(6)-10(7) pfu/TCID50 or sfu were prepared in each of the
      antiseptic/disinfectant solutions in the presence of a bovine serum/yeast extract
      mixture to simulate 'dirty conditions'. During incubation, aliquots were removed
      at predetermined timepoints up to 10 min to assess the kinetics of inactivation.
      Results indicate that all products were effective in inactivating the enveloped
      viruses herpes simplex virus type 1 and human immunodeficiency virus type 1,
      whilst being ineffective in inactivating human coronavirus, also enveloped, and
      the non-enveloped viruses. The exception to this was the benzalkonium chloride
      based product (Dettol Hospital Concentrate) which was active against the non
      enveloped human coxsackie virus. Four antiseptic/disinfectant solutions with
      chloroxylenol, benzalkonium chloride, cetrimide/chlorhexidine and povidone-iodine
      were also assessed for antiviral effect against human immunodeficiency virus in
      the presence of whole human blood. All four solutions proved to be effective
      within 1 min despite the cytotoxic nature of the compounds to the detection
      system.

PMID- 9602978
TI  - Limited effectiveness of chlorhexidine based hand disinfectants against
      methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Hand disinfectants containing chlorhexidine are thought to be less bactericidal
      against methicillin-resistant Staphylococcus aureus (MRSA) than methicillin
      susceptible Staphylococcus aureus (MSSA). We report an in vitro comparison
      between three distinct MRSA strains and three MSSA strains. The bactericidal
      efficacy of chlorhexidine digluconate, 'Hibiscrub' and 'Hibisol' against
      Staphylococcus aureus was determined in a quantitative suspension test.
      Logarithmic reduction factors (RF) were calculated for each of six parallel
      experiments. Chlorhexidine digluconate and 'Hibisol' showed RF > 5 at most
      concentrations and reaction times but 'Hibiscrub' did not. MRSA was found to be
      significantly less susceptible than MSSA to chlorhexidine digluconate,
      'Hibiscrub' and 'Hibisol' (P < 0.05; two-tailed t-test for independent samples).
      'Hibisol' was significantly more effective against MRSA than 'Hibiscrub' (P <
      0.05). Hand disinfectants containing both alcohol and chlorhexidine (e.g.,
      'Hibisol') are more effective against MRSA than scrubs based only on
      chlorhexidine ('Hibiscrub') and should be used in clinical practice.

PMID- 9602979
TI  - N-terminal sequence polymorphism in the coagulase gene of Staphylococcus aureus
      and its potential use as an epidemiological marker.
AB  - N-terminal DNA sequences of the coagulase gene were amplified from Staphylococcus
      aureus strain ISP8 (NCTC 8325-4) DNA using the polymerase chain reaction. The
      amplified DNA product (984 bp) was used to probe SmaI and DraI digested total DNA
      of methicillin- and multi-resistant S. aureus (MRSA) type strains, methicillin
      sensitive S. aureus (MSSA) clinical isolates, and community (commensal) isolates.
      A SmaI fragment of a similar size in all the isolates examined hybridized with
      the coagulase gene fragment probe. All MRSA isolates, representing closely
      related (clonal) types, revealed identical coagulase hybridization patterns with
      DraI digested DNA. MSSA and community isolates closely related to ISP8 by SmaI
      fragment analysis shared closely related DraI/coagulase hybridization patterns,
      differing from that identified for the MRSAs. In contrast, the community and MSSA
      isolates not related to ISP8 as judged by total SmaI fragment polymorphisms, were
      also diverse in their DraI/coagulase hybridization patterns. In addition, the
      intensity of the hybridization signal obtained with the MRSA isolates varied
      significantly (less than) from the other isolates, indicating the presence of
      multiple and probably different coagulase genes between the isolates. The
      findings reported here indicate that hybridization analysis using single genes as
      DNA probes is less discriminant than restriction fragment length polymorphism
      analysis of the total genome of different isolates.

PMID- 9602980
TI  - Amoxycillin/clavulanic acid prophylaxis in elective colorectal surgery.

PMID- 9602981
TI  - Please give us the right rates.

PMID- 9602982
TI  - Antimicrobial intravascular catheters--which surface to coat?

PMID- 9602983
TI  - Statistical principles for clinical trials.
AB  - If a trial is to be well designed, and the conclusions drawn from it valid, a
      thorough understanding of the benefits and pitfalls of basic statistical
      principles is required. When setting up a trial, appropriate sample-size
      calculation is vital. If initial calculations are inaccurate, trial results will
      be unreliable. The principle of intent-to-treat in comparative trials is
      examined. Randomization as a method of selecting patients to treatment is
      essential to ensure that the treatment groups are equalized in terms of avoiding
      biased allocation in the mix of patients within groups. Once trial results are
      available the correct calculation and interpretation of the P-value is important.
      Its limitations are examined, and the use of the confidence interval to help draw
      valid conclusions regarding the clinical value of treatments is explored.

PMID- 9602984
TI  - A comparison of the efficacy, tolerability and safety of azithromycin and co
      amoxiclav in the treatment of sinusitis in adults.
AB  - The efficacy, tolerability and safety of azithromycin and co-amoxiclav in the
      treatment of non-severe acute maxillary/ethmoidal sinusitis were compared in a
      randomized, open clinical trial in 254 adult patients. The predominant pathogens
      were Streptococcus pneumoniae and Haemophilus influenzae (83 patients).
      Azithromycin was administered orally to 165 patients at a single daily dose of
      500 mg for 3 days, and co-amoxiclav (4:1) to 89 patients, at a dose of 500 mg
      three times daily for 10 days. The overall clinical response rates were 87.5% for
      azithromycin and 83.7% for co-amoxiclav at follow-up (day 21-28). Microbiological
      responses to both drugs were good, with only five patients in each group having a
      persistent infection after treatment. Both drugs were well tolerated and produced
      similar incidences of adverse events, which were mostly gastrointestinal.
      Azithromycin was as effective, and as well tolerated as co-amoxiclav, and its
      shorter simpler dosing regime may offer advantages in compliance and cost.

PMID- 9602985
TI  - Adequate relief as an endpoint in clinical trials in irritable bowel syndrome.
AB  - Irritable bowel syndrome is characterized by recurrent abdominal pain and altered
      bowel function. In designing studies to evaluate new treatments for this disease,
      however, it is difficult to select appropriate endpoints to reflect improvement
      in the range of symptoms of the syndrome. In the present study we evaluated the
      parameter of adequate relief of abdominal pain and discomfort, as perceived by
      the patients, as a key endpoint for efficacy in the treatment of patients with
      irritable bowel syndrome. Abdominal pain and bowel function data were collected
      daily from 370 patients with the disease during treatment with placebo or a novel
      potent 5HT3 receptor antagonist. Once every 7 days adequate relief of pain and
      discomfort was assessed. Quality-of-life data were collected using self
      administered questionnaires. The endpoint of adequate relief was significantly (P
      < 0.05) correlated with improvement in pain severity scores, percentage of pain
      free days, percentage of days with urgency, improvement in stool frequency and
      consistency, and quality-of-life parameters. Adequate relief of pain and
      discomfort is significantly correlated with changes in multiple parameters
      associated with irritable bowel syndrome and can be used as an endpoint for
      assessing response to therapy in these patients.

PMID- 9602986
TI  - Changes in mucosal levels of transforming growth factor-alpha from the oxyntic
      region and ulcer site during duodenal ulcer healing with ranitidine or
      sucralfate.
AB  - Changes in the levels of transforming growth factor-alpha (TGF-alpha) in gastric
      mucosa during ulcer healing were studied in 24 patients with endoscopically
      confirmed duodenal ulcers, treated either with ranitidine (300 mg daily, at
      night) or with sucralfate (2 g twice daily). Endoscopic biopsies were taken from
      the gastric fundus and from the ulcer margin at baseline and after 7-10 days of
      treatment. TGF-alpha levels were determined by radioimmunoassay in paired samples
      from 22 patients (fundal) and 18 patients (duodenal). There were no significant
      changes in TGF-alpha levels in the fundus of the whole group or of either
      treatment group. At the ulcer site, however, there was a significant increase in
      TGF-alpha levels in the whole group (from 16.4 to 33 pg/mg protein (medians); P <
      0.005), and an increasing trend was seen in both treatment groups but was
      statistically significantly only in the group treated with sucralfate (P < 0.03).

PMID- 9602987
TI  - Intravesicular prostaglandin E2 for the prophylaxis of urinary retention after
      colpohysterectomy.
AB  - The aim of this study was to assess the efficacy of PGE2 in enhancing bladder
      function after vaginal hysterectomy. A total of 110 women with or without urinary
      incontinence underwent vaginal hysterectomy and cystourethropexy surgery because
      of grade II or III genital prolapse. Preoperatively the patients were randomly
      assigned to two groups: group 1 (n = 50) received on the fourth post-operative
      day, before removal of the bladder catheter, an intravesicular solution of 1.50
      mg PGE2 (2 x 0.75 mg); group 2 (n = 60) did not receive any prophylaxis for
      urinary retention. In the PGE2-treated group significantly fewer patients had
      urinary retention for 3 days or more (10%, P < 0.05) than in the control group
      (27%). The use of intravesicular PGE2 reduced the time taken to restore detrusor
      function.

PMID- 9602988
TI  - Effects of splenectomy on luteal function in pseudopregnant rabbits.
AB  - The involvement of the immune system in changes in luteal function was evaluated
      in rabbits. Pseudopregnancy was induced in 10 females and the spleens (considered
      to be the source of macrophages) of five were excised on day 7 of
      pseudopregnancy, while the five controls had sham splenectomies. Subsequent
      changes in serum progesterone concentrations were measured as an indicator of
      luteal function and luteolysis. A second pseudopregnancy was induced 31 days
      after splenectomy. The first pseudopregnancy was prolonged and during the second
      pseudopregnancy the serum progesterone concentrations on days 3 and 7 were much
      lower in the splenectomy group than in the control group. On day 14 of the second
      pseudopregnancy, the serum progesterone concentration markedly decreased in the
      control group while it remained almost at the level of day 7 in the splenectomy
      group. These results suggest that splenectomy suppresses the expression of luteal
      function and delays luteolysis in rabbits.

PMID- 9602989
TI  - Staphylococcus species on the skin surface of infant atopic dermatitis patients.
AB  - The Staphylococcus species present in microbiological samples from the facial
      skin of 10 infants with atopic dermatitis and eight healthy infants were studied.
      S. aureus colonization was detected on the cheek and nose skin of most of the
      infants with atopic dermatitis (9/10 and 7/10, respectively). Among the coagulase
      negative staphylococci found, S. epidermidis was detected commonly on the skin of
      healthy infants; several other species of coagulase-negative staphylococci were
      found on the skin of infants with atopic dermatitis and of healthy infants.

PMID- 9602990
TI  - Dose escalation induces tolerance to side-effects of erythropoietin in a patient
      with dialysis anaemia: case report.
AB  - A 51-year-old woman began haemodialysis for chronic renal failure in February
      1981. Symptomatic anaemia required treatment with recombinant human
      erythropoietin (rHuEPO) in February 1990 (3000 IU, twice weekly, intravenously).
      She developed influenza-like symptoms and treatment was withdrawn. In June 1994
      rHuEPO was resumed at a very low dose of 100 IU subcutaneously three times
      weekly, and was increased gradually to 500 IU, without inducing any side-effects.
      At this dose the haematocrit was maintained at 22.0-25.0% and the symptoms of
      anaemia improved. In patients like ours, with influenza-like symptoms caused by
      rHuEPO therapy, dose escalation starting from an ultra-low dose may be effective
      in avoiding side-effects.

PMID- 9602991
TI  - Persistent vegetative state, withdrawal of artificial nutrition and hydration,
      and the patient's "best interests".

PMID- 9602992
TI  - Need--is a consensus possible?

PMID- 9602993
TI  - Ethics committees, principles and consequences.
AB  - When ethics committees evaluate the research proposals submitted to them by
      biomedical scientists, they can seek guidance from laws and regulations, their
      own beliefs, values and experiences, and from the theories of philosophers. The
      starting point of this paper is that philosophers can only be helpful to the
      members of ethics committees if they take into account in their models both the
      basic moral intuitions that most of us share and the consequences of people's
      choices. A moral view which can be labelled as a consequentialist interpretation
      of mid-level principlism is developed, defended and applied to some real-life and
      hypothetical research proposals.

PMID- 9602994
TI  - Applying best interests to persistent vegetative state--a principled distortion?
AB  - "Best interests" is widely accepted as the appropriate foundation principle for
      medico-legal decisions concerning treatment withdrawal from patients in
      persistent vegetative state (PVS). Its application appears to progress logically
      from earlier use regarding legally incompetent patients. This author argues,
      however, that such confidence in the relevance of the principle of best interests
      to PVS is misplaced, and that current construction in this context is
      questionable on four specific grounds. Furthermore, it is argued that the
      resulting legal inconsistency is distorting both the principle itself and, more
      particularly, individual patient interests.

PMID- 9602995
TI  - Supply of medicines: paternalism, autonomy and reality.
AB  - Radical changes are taking place in the United Kingdom in relation to the
      classification of, and access to, medicines. More and more medicines are being
      made available over the counter both in local pharmacies and in supermarkets. The
      provision of more open access to medicines may be hailed as a triumph for patient
      autonomy. This paper examines whether such a claim is real or illusory. It
      explores the ethical and legal implications of deregulating medicines. Do
      patients benefit? What is the impact on pharmacists? Are the true beneficiaries
      of change largely the pharmaceutical industries?

PMID- 9602996
TI  - Francis Galton: and eugenics today.
AB  - Eugenics can be defined as the use of science applied to the qualitative and
      quantitative improvement of the human genome. The subject was initiated by
      Francis Galton with considerable support from Charles Darwin in the latter half
      of the 19th century. Its scope has increased enormously since the recent
      revolution in molecular genetics. Genetic files can be easily obtained for
      individuals either antenatally or at birth; somatic gene therapy has been
      introduced for some rare inborn errors of metabolism; and gene manipulation of
      human germ-line cells will no doubt occur in the near future to generate organs
      for transplantation. The past history of eugenics has been appalling, with gross
      abuses in the USA between 1931 and 1945 when compulsory sterilization was
      practised; and in Germany between 1933 and 1945 when mass extermination and
      compulsory sterilization were performed. To prevent such abuses in the future
      statutory bodies, such as a genetics commission, should be established to provide
      guidance and rules of conduct for use of the new information and technologies as
      applied to the human genome.

PMID- 9602997
TI  - The right to information for the terminally ill patient.
AB  - OBJECTIVES: To analyse the attitudes of medical personnel towards terminally ill
      patients and their right to be fully informed. DESIGN: Self-administered
      questionnaire composed of 56 closed questions. SETTING: Three general hospitals
      and eleven health centres in Granada (Spain). The sample comprised 168 doctors
      and 207 nurses. RESULTS: A high percentage of medical personnel (24.1%) do not
      think that informing the terminally ill would help them face their illness with
      greater serenity. Eighty-four per cent think the patient's own home is the best
      place to die: 8.9% of the subjects questioned state that the would not like to be
      informed of an incurable illness. CONCLUSION: In our opinion any information
      given should depend on the patient's personality, the stage of the illness and
      family circumstances. Our study confirms that a hospital is not the ideal
      environment for attending to the needs of the terminally ill and their families.

PMID- 9602998
TI  - Changes in medical student attitudes as they progress through a medical course.
AB  - OBJECTIVES: To explore the way ethical principles develop during a medical
      education course for three groups of medical students--in their first year, at
      the beginning of their penultimate (fifth) year and towards the end of their
      final (sixth) year. DESIGN: Survey questionnaire administered to medical students
      in their first, fifth and final (sixth) year. SETTING: A large medical school in
      Queensland, Australia. SURVEY SAMPLE: Approximately half the students in each of
      three years (first, fifth and sixth) provided data on a voluntary basis, a total
      of 385 students. RESULTS: At the point of entry, minor differences were found
      between medical students and first year law and psychology students. More
      striking were differences between male and female medical students, suggesting
      early socialization had a substantial impact here. CONCLUSIONS: Results indicate
      that substantial changes in attitude have developed by the beginning of fifth
      year with little change thereafter. Gender difference persisted. Some difference
      in ethical attitudes were found when groups of different ethnic backgrounds were
      compared. The impact of a move to a graduate medical course, which gives high
      priority to ethics within a professional development domain, can now be
      evaluated.

PMID- 9602999
TI  - The brain-mind quiddity: ethical issues in the use of human brain tissue for
      therapeutic and scientific purposes.
AB  - The use of human brain tissue in neuroscience research is increasing. Recent
      developments include transplanting neural tissue, growing or maintaining neural
      tissue in laboratories and using surgically removed tissue for experimentation.
      Also, it is likely that in the future there will be attempts at partial or
      complete brain transplants. A discussion of the ethical issues of using human
      brain tissue for research and brain transplantation has been organized around
      nine broadly defined topic areas. Criteria for human brain tissue transplantation
      and laboratory use of brain tissue are proposed.

PMID- 9603000
TI  - Autonomy in the face of a devastating diagnosis.
AB  - Literary accounts of traumatic events can be more informative and insightful than
      personal testimonials. In particular, reference to works of literature can give
      us a more vivid sense of what it is like to receive a devastating diagnosis. In
      turn this can lead us to question some common assumptions about the nature of
      autonomy, particularly for patients in these circumstances. The literature of
      concentration camp and labour camp experiences can help us understand what it is
      like to have one's life-plans altered utterly and unexpectedly. Contrary to
      common views of autonomy which have difficulty in characterising autonomous
      action when long-standing assumptions are suddenly lost, these examples show that
      autonomy is possible in these circumstances. We need a theory of autonomy which
      can deal with traumatic events and is useful in the clinical context.

PMID- 9603001
TI  - An anthropological exploration of contemporary bioethics: the varieties of common
      sense.
AB  - Patients and physicians can inhabit distinctive social worlds where they are
      guided by diverse understandings of moral practice. Despite the contemporary
      presence of multiple moral traditions, religious communities and ethnic
      backgrounds, two of the major methodological approaches in bioethics, casuistry
      and principlism, rely upon the notion of a common morality. However, the
      heterogeneity of ethnic, moral, and religious traditions raises questions
      concerning the singularity of common sense. Indeed, it might be more appropriate
      to consider plural traditions of moral reasoning. This poses a considerable
      challenge for bioethicists because the existence of plural moral traditions can
      lead to difficulties regarding "closure" in moral reasoning. The topics of truth
      telling, informed consent, euthanasia, and brain death and organ transplantation
      reveal the presence of different understandings of common sense. With regard to
      these subjects, plural accounts of "common sense" moral reasoning exist.

PMID- 9603002
TI  - CPR decision-making by elderly patients.

PMID- 9603003
TI  - Teaching introductory engineering: a problem based learning experience.
AB  - A freshman introductory engineering course is being taught on an experimental
      basis to approximately 40 cadets per semester at the United States Air Force
      Academy. The purpose of the course is to better address seven educational
      outcomes desired in Academy graduates. Problem Based Learning is used to present
      engineering as a problem solving process that involves a variety of
      interdisciplinary issues. The setting is an Air Force System Program Office
      responsible for planning a manned mission to Mars. Students are guided by a
      mentor to identify the relevant engineering requirements. Traditional instruction
      is used only to present skills and tools that enhance students' learning. An
      integrated assessment program is being used to evaluate this instructional
      approach and how well the educational outcomes are being met. The quantitative
      assessment findings are inconclusive and indicate further work is needed to
      develop reliable assessment instruments. Qualitative findings, however, show that
      the students learned important engineering fundamentals, liked the course, and
      enjoyed the Mars scenario. They also developed an appreciation for the
      interdisciplinary nature of engineering, developed confidence in their ability to
      make decisions for problem-solving, and they acquired self esteem not usually
      obtained from traditional engineering courses. This paper presents highlights
      from the three years this course has been offered.

PMID- 9603004
TI  - The effect of sustained delivery of androstanedione on the functional activities
      of adult male rats.
AB  - It is well documented that androgens stimulate protein anabolism, muscular
      development, bone growth and increased metabolic rate. In addition, exogenous low
      levels of testosterone can inhibit the secretion of gonadotropins by the anterior
      pituitary. The objective of this study was to investigate the effect of sustained
      delivery of androstanedione (AD) on the testicular architecture by means of
      tricalcium phosphate lysine (TCPL) delivery system. In this experiment adult male
      Sprague Dawley rats (250-300 g BW) were randomly divided into three equal groups
      (n = 16). Rats in group I were implanted subcutaneously with TCPL implants loaded
      with AD. Rats in group II were implanted with sham TCPL capsules, and rats in
      group III served as intact unimplanted controls. Surgical aseptic techniques were
      performed according to standard laboratory procedures. At the end of 2, 4, 8 and
      16 weeks post implantation, four animals from each group were sacrificed and the
      testes were collected, weighted, and embedded for histopathological evaluations.
      The results of this study revealed the following: (1) remarkable reduction of
      testicular mass at the end of the 4 week phase and continued for the duration of
      study in comparison to the sham and intact control; (2) cross sections obtained
      from group I animals have shown that the Leydig cells were decreased in size and
      number of organelle; (3) the epithelium of the seminiferous tubules decreased in
      height and cell number; (4) a significant decrease (p < 0.05) in the number of
      primary and secondary spermatocytes (63% and 78% receptively) at the end of the 8
      week phase, and azoospermia was observed at the 12 week phases in group I rats;
      and (5) slight reduction in the number of was observed in tissues obtained AD
      treated animals. This experiment confirms our previous findings using
      testosterone hormone and demonstrates that low sustained levels of exogenous AD
      can also impair fertility in rats.

PMID- 9603005
TI  - In vitro delivery of dexamethasone using hydroxyapatite reservoirs.
AB  - Dexamethasone has been shown to stimulate bone nodule formation in vitro. A
      hydroxyapatite (HA) reservoir drug release device was designed to release
      dexamethasone in vitro. Two HA particle sizes (< 38 microns or 63-75 microns)
      were used to fabricate the reservoirs. Each HA reservoir was loaded with 2 mg of
      dexamethasone and suspended in 100 ml of 50% aqueous ethanol at 37 degrees C for
      a period of 28 days. The positive controls indicated a limited solubility of
      dexamethasone of 1.18 mg per 100 ml of 50% aqueous ethanol. Dexamethasone was not
      released from any of the HA reservoirs for the first 24 hours. The largest amount
      of dexamethasone (0.0137 microgram/microliter) was released from the 63-75
      microns particle HA reservoirs. A significantly lesser amount (0.00855
      microgram/microliter) of dexamethasone was released from the < 38 microns
      particle HA reservoirs. The results of this study suggest that a HA ceramic
      reservoir loaded with dexamethasone can be used to deliver dexamethasone over
      long periods of time.

PMID- 9603006
TI  - A comparison of fibrous tissue formation surrounding intraperitoneal and
      subcutaneous implantation of ALCAP, HA, and TCP ceramic devices.
AB  - It is well demonstrated in the literature that ceramic drug delivery systems are
      highly compatible and non-immunogenic. Recent studies in our laboratory have
      documented the need of an experiment comparing foreign body reactions of several
      different types of ceramics used for implantation and/or drug delivery. The
      specific objective of this study was to compare the subcutaneous (s.c.) and
      intraperitoneal (i.p.) foreign body reactions and biocompatibility of the
      following implantable materials presently used in orthopedics: ALCAP (aluminum
      calcium phosphate), HA (hydroxyapatite), and TCP (tricalcium phosphate). The rats
      were divided into four groups: Group I consisted of 10 rats implanted with ALCAP
      i.p. and s.c., Group II (n = 10) animals were implanted i.p. and s.c. with HA,
      Group III consisted of 10 rats implanted i.p. and s.c. with TCP, and Group IV
      consisted of 10 control animals that were housed under the same environmental
      conditions as the three experimental groups. At 90 days post-implantation, rats
      in all four groups were euthanized. The microscopic evaluation of the fibrous
      tissue surrounding i.p. and s.c. implants revealed the following: 1) all of the
      ceramic devices had varying degrees of fibrous capsule formation at the time of
      sacrifice, 2) the thickness of the fibrous tissue capsule was dependent on the
      type of ceramic used, and 3) the thickness of the fibrous tissue capsules around
      the subcutaneous devices differed remarkably from implants placed
      intraperitoneally. The data from this study indicates that capsule formation is
      dependent upon factors such as ceramic composition and surgical implantation
      site.

PMID- 9603007
TI  - Pathophysiological changes associated with sustained delivery of estrogen and
      estrogen plus progesterone by TCPL devices.
AB  - The specific objective of this investigation was to study the role of sustained
      delivery of estrogen (E), or estrogen plus progesterone (E + P) on the histologic
      and biochemical changes associated with the reproductive organs of adult female
      rats as a model. Adult Sprague Dawley female rats were randomly divided into
      three equal groups (n = 3). Group I animals were left as intact controls, group
      II were implanted with TCPL loaded with E (release rate: 8 pg/ml), and group III
      animals were implanted with TCPL loaded with E + P. Data obtained from this study
      have shown that: (i) TCPL delivery system is capable of releasing E, and P + E at
      a sustained level for four weeks. (ii) The amounts of E or E + P released from
      TCPL capsules resulted in pathophysiological changes at the reproductive organ
      levels. (iii) Data obtained showed a slight decrease in total body weights
      following implantation of E filled TCPL devices. In contrast, no significant
      difference was observed in total body weights between rats treated with E + P and
      the control rats. (iv) The results demonstrate that the uterine weights obtained
      from E and E + P treated animals were significantly higher than the uterine
      weights obtained from the control animals. Unlike uterine weights, the wet
      weights of ovaries were remarkably regressed in all E and E + P treated animals
      in comparison to the control animals. Ultrastructurally, suppression of theca
      cells as well as inhibition of proliferative activity of granulosa cells were
      observed in the ovaries of the animals that received E alone in comparison to P +
      E and the control group. (v) Histological findings revealed changes in vaginal
      smears and the vaginal, fallopian tube and endometrial epithelium. This was
      evidenced microscopically by the hypertrophic, papillary projections, cytoplasmic
      vacuolation (fluid retention) and a decrease in ovarian follicles in animals
      exposed to sustained delivery of E in comparison to control and E + P groups.
      Overall, our observations of the results of this study suggest that sustained
      levels of P + E by TCPL capsules were able to regulate fertility regardless of
      suppression of endogenous levels of the ovarian hormones.

PMID- 9603008
TI  - The synergistic effect of sustained delivery of DHT, DHEA, and E on the ventral
      prostate of adult male rodents.
AB  - Previously, our laboratory has reported that tricalcium phosphate lysine drug
      delivery system (TCPL) can be used successfully to deliver dihydrotestosterone
      (DHT) and testosterone (T) at a sustained manner for long duration. The objective
      of this study was to evaluate the effects of estrogen (E), DHT and
      dehydroepiandrosterone (DHEA), delivered in a sustained manner, individually or
      in combination, by means of TCPL delivery system on the morphological changes of
      ventral prostatic tissue. Adult male rats (BW 300-350 gm) were randomly divided
      into four equal groups. Animals in Group I served as our intact unimplanted
      controls. Capsules implanted in Group II rats were loaded with TCPL containing
      100 mg of DHEA. Rats in Group III were implanted with TCPL loaded with 100 mg of
      DHEA and 500 mg of DHT, while rats in Group IV were implanted with TCPL loaded
      with 100 mg of DHEA, 500 mg of DHT and 200 mg of E. Surgical aseptic techniques
      were performed according to standard laboratory procedures. The animals were
      maintained at the University of Mississippi Medical Center Animal Facilities
      following the rules and regulations established by NIH on the Care and Use of
      Laboratory Animals. At the end of 8 weeks post implantation, all animals were
      sacrificed and the prostatic tissues were collected, weighed and embedded for
      histopathological evaluations. Statistical analysis was conducted by using
      standard computer programs (STATEVIEW, JANDEL, ANOVA at 95% CI). The data
      obtained in this investigation demonstrated that exogenous intake of E + DHEA +
      DHT delivered in a sustained manner for eight weeks induced several
      pathophysiological conditions in ventral prostatic tissue in comparison to
      prostatic tissue collected from control animals. Cytopathological evaluations of
      tissue collected from Group II animals demonstrated the following: (i) atrophic
      pattern of the epithelium, (ii) small, round glands with low cuboidal epithelium,
      (iii) hypertrophy alone or in conjunction with occasional hyperplasia of the
      epithelial cells, and (iv) an increased presence of connective tissue stroma. In
      contrast, ventral prostate collected from animals in Group IV showed an increase
      in weights of the net prostatic tissues in comparison to the control group.
      Histopathological observations such as pleomorphism, low cuboidal to
      pseudostratified glands, prostatic hyperplasia of the epithelial cells,
      occasional mitotic activity, and occasional presence of connective tissue stroma
      were detected. In conclusion, the results of this study suggest that the use of
      TCPL capsules loaded with steroid hormones, individually or in combination can be
      used to regulate the growth and functional behavior of prostatic tissue in male
      rodents.

PMID- 9603009
TI  - TCPL delivery system: the role of DHT, DHEA, and E on the epididymal tubules of
      adult male rats.
AB  - Recent studies reported from our laboratory have established that the sustained
      delivery of danazol in combination with androgens resulted in the remarkable
      reduction of epididymal mass. In addition, previous studies have recommended that
      ultrastructural of epididymal tubules have to be elucidated. The specific
      objective of this investigation was to evaluate the cytological characteristics
      of epididymal tissues exposed to sustained delivery of dihydrotestosterone (DHT),
      dehydroepiandrsterone (DHEA) and a combination of Estrogen (E), DHEA plus DHT by
      means of tricalcium phosphate lysine (TCPL) delivery system. Adult male rats (BW
      300-350 gm) were randomly divided into four equal groups: Group I animals were
      implanted i.p. with TCPL loaded with DHEA (100 mg). Animals in group II were
      implanted with TCPL capsules loaded with DHEA (100 mg) + DHT (500 mg). Group III
      animals were implanted with TCPL capsules loaded with E (200 mg) + DHEA (100 mg)
      + DHT (500 mg). Group IV animals served as the intact unimplanted controls.
      Surgical aseptic techniques were performed according to standard laboratory
      procedures. The animals were maintained at the University of Mississippi Medical
      Center Animal Facilities following the rules and regulations established by NIH
      on the Care and Use of Laboratory animals. At the end of 6 weeks post
      implantation, all animals were sacrificed and the epididymal tissues were
      collected, weighed, and embedded for histopathological evaluations. Statistical
      analysis was conducted by using standard computer programs (STATVIEW, ANOVA at
      95% CI). The data obtained in this investigation demonstrated the following: (1)
      remarkable reduction in sperm counts and motility obtained from epididymal
      tubules in all experimental (hormonally treated) groups, (2) the lumen of the
      epididymal tubules were devoid of sperm in animals treated with DHT in comparison
      to the control, (3) a decrease in the diameter of tubules with occasional
      hypertrophic epithelium in all experimental animals, (4) disorganization of
      nuclear material was observed in animals treated with DHEA and DHEA + E + DHT in
      comparison to the control group. The overall observation of this study suggests
      that sustained delivery of DHEA, DHEA + DHT, and DHEA + DHT + E can be used to
      regulate the structural and functional architecture of the site of
      extramaturation of spermatozoa.

PMID- 9603010
TI  - Interaction of cells with UHMWPE impregnated with the bioactive peptides RGD, RGE
      or Poly-L-lysine.
AB  - Several reports have suggested that encapsulation of orthopaedic and dental
      implants with fibrous tissue can lead to implant failure. The binding of cells to
      the surface of the implants is specific to amino-acid sequences, typically RGD.
      The specific objective of this study was to investigate the interaction of
      cultured human peripheral macrophages with specific amino-acid sequences to
      determine if adherence is due to the specificity of such sequence. Macrophages
      were seeded at a density of 1 x 10(5) cells on ultra high molecular weight
      polyethylene (UHMWPE) coated with either amino-acid heteropolymers of RGE, RGD,
      or amino-acid homopolymer Poly-L-Lysine. Cells were observed daily and morphology
      was recorded. The results showed that cells growing in the presence of RGD had
      significantly (p < 0.05) higher numbers of cells adhering and remaining viable,
      in comparison to cells growing on Poly-L-lysine or RGE. Cells growing on UHMWPE
      coated with RGE appeared irregularly (elongated and spindle) shaped and unevenly
      spaced. The cells growing in the presence of Poly-L-Lysine showed cellular
      disruption and lysis, whereas cells growing on the RGD appeared intact, regularly
      spaced and began fusing into giant cells. Lactate dehydrogenase activity was used
      as a measure of membrane integrity, and cells grown on UHMWPE coated with Poly-L
      lysine showed a two-fold increase in activity over control and peptide treated
      groups. Immunochemical analysis for cytokine (IL-1) release as a measure of
      cellular reactivity revealed an increase level in the experimental groups after
      24 hours and remained measurable over the duration of the experiment. Cells
      incubated on uncoated polyethylene showed no evidence of increased cytokine
      response. Overall, the results show macrophages can interact with specific
      coating on the material surface, and these surfaces can affect the adhesion
      process adherence. Use of RGE, which inhibits binding of the cells, may be a
      factor that can be used to coat implants to increase their longevity.

PMID- 9603011
TI  - Fibrous capsule formation in response to ultrahigh molecular weight polyethylene
      treated with peptides that influence adhesion.
AB  - A wide variety of hard tissue substitute materials for reconstruction have been
      designed for use in dental and orthopaedic procedures. Most of the literature
      provides information on the osteocompatibility of these materials, and not on
      soft tissue compatibility. The bone bonding strength of the materials is
      relatively high, but there seems to be a lack of bonding properties with soft
      tissue which results in the formation of fibrous encapsulation. This lack of soft
      tissue bonding can lead to implant failure. Therefore in order to study how
      artificial materials may remain in the body for long periods of time and remain
      functional, it is vital to understand the fibrous tissue encapsulation process.
      Ultrahigh molecular weight polyethylene coated with RGD, RGE, Poly-L-Lysine, or
      saline was implanted into Sprague Dawley rats either intraperitoneally or
      subcutaneously for 12 weeks. Aseptic surgical techniques were followed according
      to standard laboratory procedures. Blood was collected weekly for the first 8
      weeks and at 12 weeks, and analyzed for lactate dehydrogenase activity to assess
      muscle wasting and compatibility. Lactate dehydrogenase activity was elevated at
      weeks one and two for groups implanted with materials, in comparison to control
      unoperated animals. From weeks 3-12, the LDH activity was similar in all groups
      indicating that there was no adverse response to the implanted material. The
      implants were harvested at the end of 12 weeks, and the fibrous capsule was
      screened histologically to determine thickness and cell types at the interface.
      The results clearly showed that the implants that were placed subcutaneously had
      a less extensive fibrous and vascular tissue formation, than those implanted
      intraperitoneally. The results also indicated that the location of the implant
      intraperitoneally, determined the extent of the fibrous tissue formation. The
      implanted materials coated with RGD and Poly-L-Lysine had thicker fibrous capsule
      formation than RGE coated implanted at both the subcutaneous and intraperitoneal
      sites. The results also suggest that the implant-interface contained fewer
      inflammatory cells when the implants were placed subcutaneously. The overall
      results indicate that more than surface charge or coating govern the formation of
      fibrous tissue in vivo.

PMID- 9603012
TI  - Biochemical analysis associated with HL-60 cells incubated with various ceramic
      materials.
AB  - The purpose of this experiment was to determine the effect of TCP, ALCAP, and HA
      ceramic particles on the viability and proliferation rate of HL-60 cells in
      culture. Previous experiments have suggested that growing cell lines such as
      macrophages, fibroblasts, and endothelial cells on discs made of TCP, ALCAP, and
      HA induced immunochemical and morphological changes. The effect of ceramic
      particles (< 38 um) on HL-60 cells in culture have never been investigated. A
      total of 1 x 10(5) (n = 5) cells were placed in culture with 2 mg of ALCAP, TCP,
      HA particles, or 10 micrograms/ml lipopolysaccharides (LPS). At the end of 24,
      48, and 96 hours, the cells were evaluated morphologically and then counted. The
      supernatants were collected and biochemical analysis for LDH and immunochemical
      analysis for cytokines IL-1 was performed. The data from this investigation
      revealed the following: (1) At the end of the 24 hour phase, the cell number in
      wells containing HA and ALCAP particles were lower than the control cells,
      whereas cells in the presence of TCP were similar to the control. (2) Microscopic
      evaluation of cells treated with HA showed hydropic change at 24, 48 and 96
      hours. (3) At 96 hours, there were no significant changes in cell number between
      the groups. This phenomenon could be attributed to the depletion of nutrients
      within the wells or possibly the cells reaching confluence. (4) The ease of
      ingestion of macrophages to CPB is as follows: TCP > ALCAP > HA. (5) Biochemical
      analysis of markers for cellular disturbances revealed that there were no
      significant differences between the different group at any time point (p < 0.05).

PMID- 9603013
TI  - Hydroxyapatite-oil composites for delivering AZT in simulated body fluid.
AB  - Hydroxyapatite (HA) has been used to deliver therapeutic drugs both in vitro and
      in vivo at a constant rate showing zero order kinetics. This study was designed
      specifically to analyze the effects of wheat germ (WG) incorporation with HA on
      the rate of delivery of AZT from an insert system over a one month period in
      vitro. Insert systems which were saturated with wheat germ oil delivered AZT at a
      slower rate over the one month period than did half-saturated or unsaturated
      insert systems. All systems containing 50 mg of AZT in the outer shell delivered
      80% of the 100 mg AZT dosage over the first eight days. The systems which had a
      100 mg AZT insert surrounded by an oily HA shell lacking AZT delivered AZT in a
      linear manner over the course of one month. The amounts and rates of AZT release
      from composites was indirectly proportional to the amount of wheat germ oil used.
      The results of this study show that the lipids incorporated in the ceramic
      composites can be tailored to deliver a 100 mg AZT dosage for a period of one
      month in vitro.

PMID- 9603014
TI  - A ceramic system for delivering interleukin-2.
AB  - Interleukin-2 (IL-2) is a potentially effective cytokine to be used for cancer
      treatment. Since keeping IL-2 doses at a low, continuous level is important to
      avoid side effects which accompany high IL-2 doses, a ceramic which release IL-2
      could prove to be a beneficial method of drug delivery for cancer patients [1].
      In vitro studies were performed to determine the optimal hydroxyapatite (HA) to
      IL-2 ratio for continuous release of IL-2 from HA using both a matrix and insert
      ceramic pellet. In the matrix pellet experiment, HA to IL-2 ratios of 25:1, 50:1
      and 100:1 were tested by compressing a homogenous mixture of each variable in
      triplicate and placing each ceramic in 2.5 mL simulated body fluid (SBF) at 37
      degrees C. The fluid was collected and replaced for each ceramic every two hours
      for 12 hours and at 24 hours. The collected fluid was then assayed for IL-2
      content. Pellets consisting of 25:1 ceramic to drug ratio delivered almost the
      entire amount of IL-2 at the fastest rate. Composites of 100:1 IL-2 to HA
      delivered the least amount of IL-2 at the slowest rate. Release of IL-2 from the
      50:1 ratio pellets was intermediate with respect to speed and amount of delivery.
      In the insert pellet experiment, similar laboratory procedures were used to show
      that 100:1 ratio insert pellets delivered IL-2 at a slower rate and in lesser
      amounts than 50:1 ratio insert pellets. Results of this study show that HA can
      deliver IL-2 at different rates by varying the ratio of HA to IL-2 in both matrix
      and insert ceramic pellets.

PMID- 9603015
TI  - Parameters of protein delivery using hydroxyapatite in simulated body fluid.
AB  - Various studies have been conducted using hydroxyapatite (HA) to deliver
      therapeutic drugs over a long period of time. However, the rate of drug release
      from ceramics varies tremendously. Thus a study was designed to observe the
      effect of particle size, pressure, drug ratio, and the addition of a zinc
      stearate binder on the release of BSA from ceramics. Samples were collected every
      two hours for a 12 hour period. Three particle sizes were used in the study (<
      38, 45-63, and 63-75 microns). Variations in particle size did not influence the
      release of BSA. Ceramics compressed at a pressure of 150 Mpa delivered more
      protein than pressures of 300 MPa, 450 MPa, and 900 MPa. Drug to ceramic ratio
      had the most significant effect. A ratio of 1:25 BSA to HA delivered the protein
      quickly whereas the 1:100 BSA to HA delivered BSA to HA delivered BSA slowly and
      in zero order kinetics. The addition of the zinc binder improved the quality of
      the composite and decreased the release rate of protein delivery when present in
      5% or less of the total ceramic weight. HA ceramics can be used to deliver
      proteins at different rates by varying compression pressure and drug to HA ratio.

PMID- 9603017
TI  - A method to control irradiation time for laser photocoagulation on the retina.
AB  - When performing laser photocoagulation on the retina, the dynamic reflectance of
      the lesion formed by the laser may be used as a control signal. Using digital
      filter and estimation techniques on the sampled reflectance signal, the latency
      time and growth rate of the lesion reflectance are determined. These parameters
      are then used to estimate the absorption coefficient of the illuminated tissue.
      From these estimates, the irradiation time of the laser can be accurately
      determined so that optimum therapeutic effect may be obtained, without
      overexposing the tissue. The result is consistent lesion formation over any part
      of the retina.

PMID- 9603016
TI  - The preliminary study and tentative animal study on the sintered PDLLA/TCP
      composites as bone fracture internal fixation.
AB  - Polyesters based on the lactic acid have been reported safety and biodegradation
      in the human beings for two decades. The greatest advantage of the material is
      its degradation only conducted by the hydrolysis, where the ester backbones are
      supposed to be unchained in the aqueous condition. The final degradable products
      are carbon dioxide and water which can be metabolized and digested in the
      physiological environment. The goal of this study was aimed to develop a
      composite sintered with poly-DL-lactide (PDLLA) and tricalcium phosphate (TCP)
      ceramic particles as orthopedic application. The TCP particles in a range of 30
      60 wt% (with 5 wt% increment) were doped into the PDLLA matrix for the
      reinforcement, which were prepared by the melting and hot pressing techniques.
      The basic mechanical strength, biodegradable behavior, and biological response of
      the composites will be investigated in the study. Various techniques, such as pH
      meter, UV, FTIR, XRD ect., were used to examine and record the degradable process
      of the composites soaked in the saline for 1-16 weeks. The rabbit femur condyle
      fracture fixation test was used to evaluate the tissue compatibility and the
      effects of bone fracture fixation of the composites. The histological observation
      and x-ray photography were applied for investigating assistance. In the
      histological evaluation of rabbit femur condyle fracture fixation test, the
      surface of the composite with 50 wt% TCP addition was attached by the new
      generated bone without fibrous tissue around after 8 weeks implantation. The
      fracture bone was gradually healing and the composite always firmly and properly
      fixed on the fracture area during the implanted period, which provided a breeding
      environment for normal bone remodeling. The developed composite was thought to be
      an alternative material for orthopedic application in the future, especially in
      bone screw and bone plate.

PMID- 9603018
TI  - Design of a closed system water tunnel for lamprey swimming analysis.
AB  - This work presents a swim mill design that can be used to study locomotor
      behavior in intact awake lamprey. The design is constrained by the swimming
      characteristics and anatomy of young adult lamprey and allows for
      electrophysiological monitoring of muscle activity and imaging of motor behavior.
      The design has a test section for animal containment and monitoring of motor
      behavior, a water reservoir, a water pump, and equipment for biological
      adaptations (water purification, chilling, & aeration systems). The 36 sq. inch
      acrylic test section is preceded by a turbulence-reducing converging nozzle,
      while a 1400 gallon reservoir maintains the system's hydrostatic head and acts as
      a settling chamber. This swim mill design will be used to examine lamprey
      swimming behavior under different environmental conditions (e.g., water velocity,
      turbulence, external perturbations).

PMID- 9603019
TI  - Quantitative analysis of truck driver EEG during highway operations.
AB  - Scalp electroencephalograms (EEGs) were collected from each of 80 male,
      commercial truck drivers during one week of open-highway driving (4 or 5 round
      trips per week; about 50 hours of driving per driver) as part of the Driver
      Fatigue and Alertness Study funded by the Federal Highway Administration.
      Features of the central EEG were selected for extraction based upon known
      characteristics of the EEG spectrum during sleep onset. Data reduction focused on
      the contributions to total EEG power from the theta, alpha, sigma and beta
      spectral bands. The means and regression slopes for the EEG measures were
      calculated on the time axis and used to estimate EEG values at the beginning and
      end of each leg of each trip for each driver. The weekly patterns of EEG power
      appeared to be interpretable by reference to expected circasemidian rhythms. The
      EEG sigma/beta ratio may provide an index of midafternoon sleepiness while
      driving.

PMID- 9603020
TI  - Average power spectral density of physiological tremor in normal subjects.
AB  - The measurement technologies currently available to quantitatively evaluate
      neurological tremors have several limitations. For this reason the assessment of
      disorders involving tremor is largely based on subjective clinical evaluation of
      the patient. The availability of a high-sensitivity, portable and easy to use
      instrument based on force plate technology, coupled with a customized data
      analysis protocol could represent a useful tool for the clinician. To verify such
      a hypothesis, baseline physiological tremor information in a standing posture was
      collected from normal subjects. A lightweight portable force plate was built and
      used in collecting vertical ground reaction force data, which was subsequently
      analyzed for frequency content and power spectral distribution. Repeatability of
      results in a group of subjects without any diagnosed neurological disorders, and
      intra-subject repeatability, as well as influence of footwear were investigated.

PMID- 9603021
TI  - Multiresolution EEG comparison of rat ischemia models.
AB  - Fourier transform of Electroencephalography (EEG) restricts EEG analysis due to
      its stationary properties with time change. It makes analysis difficult to
      ascertain the global effects of transient change in EEG signals. This study
      tested that multi-resolution analysis distinguishes different depths of ischemic
      insult related to the degree of residual blood flow in animal models. The results
      suggest that multi-resolution analysis demonstrate that little blood flowing to
      the brain has more detrimental effect to the EEG properties than no blood
      flowing, which is contrary to the common sense.

PMID- 9603022
TI  - Increased variability in motor output with brain-spinal cord interaction.
AB  - Spinal cord neural circuitry of the lamprey that forms a central pattern
      generator for locomotion interacts with reticular neurons forming a reticulo
      spino-reticular loop. We examine the hypothesis that increased variability exists
      in the locomotor output in the presence of this loop. Fictive locomotion
      (rhythmic activity recorded from ventral roots (VR)) was induced in in-vitro
      brain-spinal cord preparations of adult lampreys, by bathing the spinal cord with
      excitatory amino acids. In the control conditions the brain was bathed with
      physiological saline. Subsequently, synaptic reticular neuron communication was
      suppressed by application of a zero Ca2+ saline or, the brain was detached. The
      mean value of the predominant period was given by the lag to the first peak in
      the autocorrelation of the full wave rectified, moving averaged VR activity (zero
      mean, normalized). Variability in signal amplitude and burst duration or cycle
      period is indicated by attenuation of the peak values at lags > zero and the rate
      of decay of the autocorrelation. Also, power spectral density calculations were
      used to determine the dominant frequencies. Increased variability is indicated by
      wider peaks and higher power in a broader frequency band. Each index indicated
      the presence of increased variability when the reticular-spinal loop was
      functional.

PMID- 9603023
TI  - ECG compression and recognition using complete tree representation.
AB  - This paper deals with a novel method of Electrocardiogram (ECG) representation,
      compression and recognition using Complete Tree algorithm. The construction of
      Complete Tree is like overlaying a ECG waveform on a grid. The waveform is
      observed through the grid structure with vertical and horizontal grid lines. In
      addition to nodes created for each interval enclosed by that waveform on a
      quantisation level, nodes are also created for each point where the waveform cuts
      the vertical grid line between the current quantisation level and the next
      quantisation level. A leaf node represents the data sample of ECG at that
      position. For reconstruction of this ECG waveform, only the leaf nodes are used
      resulting in ECG compression. This representation is also useful in ECG pattern
      matching and recognition without reconstructing the original waveform. The ECGs
      with sampling rate of 500 sps are used. A compression ratio (CR) of 4.8:1 with
      percent RMS difference (PRD) of 8.45% is obtained. The reconstruction of original
      ECG waveform from its tree representation shows high fidelity in all its
      complexes of ECG. The results are compared with all other compression techniques
      such as AZTEC, TP, FAN, DPCM etc. By using Tree merging and splitting algorithms,
      the matching and recognition of ECG is implemented.

PMID- 9603024
TI  - EEG analysis using non-uniform oversampled filter banks.
AB  - Time-frequency or time-scale methods are well suited for short events as well as
      for large waveforms detection tasks. Filter banks analysis is an easy and quick
      computing way to implement these methods. We propose a non-uniform oversampled
      filter banks to analyze EEG single channel signal, the different subbands
      matching the classical EEG rhythms. We use oversampled filter banks to preserve
      the temporal shapes information. In order to illustrate this method, we show
      different spindle temporal structures as also their meaning in terms of sleep
      stage detection.

PMID- 9603025
TI  - An improvement of the acoustic fetal heart rate monitoring using statistical
      evaluation of the abdominal signal.
AB  - An improved acoustical method for fetal heart rate (FHR) measurement is
      presented. The beat identification is based on the selection of the power peaks
      measured on two frequency channels. The identification of the valid peaks will be
      accomplished by rules, considering the timing and the amplitudes of the detected
      peaks with preferred search for pairs of the first and second sound. The
      introduced certainty factor as a function of the statistical probabilities that
      are related to the expected peaks, provides the reliability of the determined
      repetition time. Under a given certainty the result will be ignored and the FHR
      curve will be extended or left blank. The simplifications in the algorithms of
      the process reduce the required power consumption that enables its implementation
      in a low-power microcircuit and in this way to produce a battery-operated
      portable CTG instrument for long-term FHR monitoring on a passive.

PMID- 9603026
TI  - Electrical current density model from surface electrodes.
AB  - The goal of this research is to determine the optimum electrical current for
      subthreshold electrical stimulation. The first step is to collect atrophied
      muscle impedance data from children with neuromuscular disorders using
      Bioelectric Impedance Analysis (BIA). Then to incorporate this impedance data
      into a model using the 3-D Finite Element Method (FEM). This will allow the
      evaluation of electric current densities in the target muscle resulting from
      Therapeutic Electrical Stimulation (TES). Using the FEM, optimum electrical
      stimulation parameters, levels, and electrode placement can be determined. The
      FEM will provide the first means to determine the quantity of electric current
      flowing through the target muscle from surface electrode stimulation. TES is
      adding new life to electrical stimulation therapy. TES is low intensity
      (subthreshold), long duration transcutaneous stimulation using surface
      electrodes. TES effects muscle growth and peripheral nerve sprouting leading to
      increased functional control and sensation. The initial parameters used in TES
      have been proven clinically to be effective for use in rehabilitation therapy for
      people with neuromuscular disorders. This research is the first step towards
      optimization of the TES protocol. Ultimately, the results will lead to improved
      quality of life for children with neuromuscular disorders.

PMID- 9603027
TI  - Oversampling data acquisition to improve resolution of digitized signals.
AB  - The ability to capture analog signals in a digital format suitable for subsequent
      storage, processing and analysis by a computer has revolutionized many scientific
      fields, including biomechanics. In the process of going from the analog signal to
      its digital representation, it is essential to maintain as much of the original
      signal content as possible. There is always a loss of information associated with
      the conversion from analog to digital, independently of how it is actually
      performed. The only possibility to reduce the loss of information is to increase
      the number of states or the resolution of the digital signal. The method
      presented here, based on the same theory used in oversampling analog to digital
      converters, is applicable to digital signals acquired using any converter. In
      most situations this method provides a feasible and inexpensive technique to
      significantly improve the amplitude resolution of the analog to digital
      conversion. This can be of fundamental importance when the information of
      interest is small in amplitude compared to the overall signal, or when subsequent
      ill-conditioned operations, like the computation of the derivatives of the
      signal, are to be performed.

PMID- 9603028
TI  - Beat by beat QT interval detection and characterization.
AB  - A novel algorithm for detection and analysis of QT interval, a risk factor for
      sudden cardiac death, is developed using the multiresolution wavelet approach.
      The characteristic points for detection of QT interval, i.e., the onset and
      offsets of the QRS complex and the T wave are detected by analyzing the wavelet
      transform of the ECG at particular scales. The results of the detailed study
      using standard data base indicate that proposed technique can be used to monitor
      critical heart patients for localization of problems in the duration of
      ventricular activation. The algorithm has been implemented on TMS320C25 based add
      on DSP card to PC to provide the beat by beat analysis and display of QT interval
      data.

PMID- 9603030
TI  - Neuromagnetic focusing for selective transcranial stimulation of muscles.
AB  - A focusing method for spatially selective, fast and efficient neuromagnetic
      stimulation is described that is using novel excentric coil systems. Electrolytic
      tank phantoms indicate good subcutaneous focusing without surface stimulation at
      cutaneous and shallow subcutaneous levels. Preliminary in vivo tests in humans
      indicate that selective transcranial stimulation of such closely adjoining muscle
      group areas as the ones of the musculus abductor pollicis brevis (thumb) and the
      musculus interosseous I (index finger) is possible with at least 50% less power
      than with conventional systems, with higher repetition rates and with limited
      electronic tuning of the subcutaneous focusing depth. Use of this method might
      lead to new applications in neurology and rehabilitation medicine.

PMID- 9603029
TI  - Muscle fatigue monitoring using wavelet decomposition of surface EMG.
AB  - Monitoring the local muscle fatigue in maximum voluntary isometric contraction is
      successful using median frequency and mean power frequency of the surface EMG.
      However, it has very limited success in maximum voluntary dynamic contraction. We
      showed that the relaxation electromechanical delay was a reliable fatigue
      indicator during the maximum voluntary isokinetic concentric contraction. In this
      paper, we use wavelet decomposition to generate fatigue indicators including
      contraction delay (WCD), relaxation delay (WRD), and the power ratio related to
      high frequency and low frequency regions (HF/LF) of the power spectrum of surface
      electromyogram (SEMG). Eight subjects were asked to perform right knee isokinetic
      contractions at two angular velocities (120 and 240 degrees/sec). Total work
      (TW), knee angle, and four channels of quadriceps SEMGs were sampled
      simultaneously. The results indicate that the initial slopes of WCD and WRD
      increase and are correlated with TW significantly, the initial slope of HF/LF
      declines and is correlated with TW significantly, and the WRD is more stable than
      the WCD. It concludes that wavelet decomposition enhances the features of surface
      EMG, and that power ratio (HF/LF) and contraction and relaxation delays obtained
      with the EMG wavelet decomposition can be used to monitor the muscle fatigue
      during the maximum voluntary isokinetic concentric contraction.

PMID- 9603031
TI  - Analysis of biological particles using dielectrophoresis and impedance
      measurement.
AB  - A novel electrical technique for detecting the collection of particles by
      dielectrophoresis (DEP) is described. The method is based on the impedance
      changes resulting from this collection in a microfabricated, integrated dual
      channel electrode structure. The results show good agreement with measurements of
      DEP collection by optical method for suspensions of bacterial species B.
      subtilis, E. coli and abiotic latex beads, but with substantially reduced
      experimental uncertainties. The technique overcomes the restriction on particle
      size of optical techniques and can potentially be used to investigate highly sub
      micron sized particles like viruses and DNA fragments. The dual-channel electrode
      cells can be integrated with other structures for analysing sub-micron scale
      particles, for example chip-based capillary electrophoresis.